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a technique to position single quantum dots in microdisks has been developed . optical studies have confirmed the presence of only one qd in the microdisk . one major application of this technique is the possibility to compare theoretical and experimental measurements on the lifetime modifications , as the coupling of the dot to the field depends strongly on the dot position . further studies should enable us to reach the strong coupling regime for a single dot in a microdisk . part of this work was performed within the nanometer structure consortium in lund , sweden and was supported by nfr , tfr , nutek and ssf . one of us ( vz ) acknowledges funding from the european union s marie curie fellowship .
we have fabricated and studied the photoluminescence from microdisks containing single , selected self - assembled quantum dots . using two electron beam lithography exposures and a two - step selective wet etching process , the dots were positioned at the microdisks edges with sub - micron precision . the selection and positioning of quantum dots enables an optimum coupling of the dot emission to the microdisks whispering modes . microdisks offer a very efficient optical confinement at their periphery , yielding high quality factors @xcite . q - values as high as 17000 have been reported for microdisks with inas quantum dots @xcite and values as high as @xmath0 have been reached with sio@xmath1 microdisks @xcite . this results in sharp emission lines and low lasing thresholds @xcite . quantum dots are especially well suited for microdisks as they introduce less absorption than quantum wells . coupling a single quantum dot to the whispering modes of a microdisk would enable an optimum coupling of a single emitter to the maximum quality factor value that can be attained . single quantum dot based devices offer new functionalities such as single photon emission @xcite , a single dot is an exciting tool to study cavity quantum electrodynamics effects , as has been done with single atoms in cavities @xcite . the controlled coupling of a single emitter to a high quality factor cavity also enables a careful study of lifetime modifications . the inherent random positioning of self - assembled quantum dots makes it difficult to position dots in a cavity . all lifetime modification studies reported so far have been done with randomly positioned dots in cavities @xcite . a precise control of the dot position enables an optimal study of the emitter - cavity coupling @xcite , we achieve this goal by positioning the cavity respective to the dots . other techniques that have been used to position microstructures in relation to selected qds @xcite was considered unsuitable for producing high - quality microdisks . the sample was grown by metal organic vapor phase epitaxy on a gaas wafer . a gaas buffer layer was first deposited followed by a 100 nm thick gainp layer serving as an etch stop during the pillar etching , and 600 nm of gaas was then deposited , in order to set the height of the pedestal . this value was chosen to avoid optical coupling with the substrate while still providing an efficient thermal contact between the microdisk and the substrate . finally , 90 nm of gainp were deposited with a low density of inp dots in the center of the layer . a coordinate system was fabricated on the sample using electron beam lithography . gold marks were produced in regular arrays by thermal evaporation of gold followed by liftoff . the sample was then mapped with a micro - photoluminescence setup with sub - micron resolution . the photoluminescence from single dots and white light reflection from the metal markers was imaged simultaneously . these images gave the position of quantum dots relative to the metal markers , an image is shown in fig . 1a . a second electron beam lithography exposure was made to define the microdisks . the gold marks were easily imaged through the resist with the electron microscope and were used as alignment markers to produce disks containing the selected dots in their periphery , where the whispering modes are most intense . circular sio masks with 5 micron diameter were obtained following liftoff . the structures were produced by wet etching to obtain high q values @xcite . a non selective etchant was used to etch through the gainp and into the gaas before the sio mask was removed . the pedestal was then formed by selective etching . details of the processing have been published elsewhere @xcite . a complete microdisk structure containing a single quantum dot is shown in fig . 1c . fig . 1 a and b were taken on the same location , during mapping and after completing the processing . the dots are numbered and comparing the two images clearly shows that all the dots have been successfully placed at the microdisks edges . photoluminescence experiments were done in a liquid helium cooled cryostat at a temperature of 10 k. the luminescence was collected using a microscope objective with 0.4 numerical aperture . the excitation source was a frequency doubled nd : yag laser emitting at 532 nm . spectra were acquired with a cooled ccd and a monochromator . images were taken with a video camera and a bandpass filter ( 10 nm fwhm ) centered at 720 nm . inp quantum dots are especially well suited for this kind of experiment as they have been shown to emit single photons at the ideal wavelength for silicon detectors @xcite . lasing of the gainp in the disks we study here has been reported @xcite . fig . 1d shows spectra obtained on a microdisk containing a single quantum dot . only a few sharp peaks are visible at low pumping power , which is typical for a single inp qd of this size @xcite . the possibility to achieve strong coupling with a single quantum dot has been discussed by grard et al . @xcite . microdisks are the best candidates , as micropillars have too large linewidths and microspheres have too large mode volumes . we predict that by placing a single quantum dot in the maximum field of a microdisk resonator of the right diameter , strong coupling could be achieved for a single quantum dot . in an other microdisk sample , with random distribution of qds inside the cavities , the structure in fig . 2 was observed . such structures would be possible to create in a controlled way by using the demonstrated processing scheme . this might prove particularly useful for evaluating quantum information processing schemes based on this type of structure @xcite .
nephrolithiasis is a significant health problem which has been afflicting humankind for many centuries . approximately 85% of human kidney stones are a combination of calcium oxalate monohydrate ( com ) crystals with calcium phosphate ( ca p ) phases as a nucleus . although calcium oxalate stone formation is a very common health problem , the mechanism of stone formation is still poorly understood . to better understand how renal stones form in vitro , the role of calcium phosphate on the process of calcium oxalate nucleation and crystal growth must be further investigated . p phases play a critical role in the formation of large aggregate renal stones and also influence stone size . p crystal phases , brushite ( dcpd , cahpo42h2o ) or hydroxyapatite ( hap ) , may serve as heterogeneous nuclei that initiate the precipitation of calcium oxalate monohydrate ( com ) . the influences of these minerals on calcium oxalate mineral formation is challenged by speciation ccalculations based on reported phosphate concentrations in human urine and the relative supersaturation ( ) of the suggested ca p phases ( supporting information , figure s1 ) . in healthy acidic uric conditions , urine is undersaturated with respect to dcpd mineral formation , and is slightly supersaturated with respect to hap , with supersaturation less than 5.0 . the induction time of hap nucleation at such concentrations is known to be more than several weeks or longer . the formation of dcpd under these conditions is unlikely : calcium and phosphate concentration would need to increase 510 times higher than the normal concentration of calcium and phosphate in urine for the solution to be supersaturated with respect to dcpd ( supporting information , figure s1c , d ) . p minerals is relatively low in urine , suggesting that the initial crystal ca p phases such as amorphous calcium phosphate , inducing the heterogeneous nucleation of com . the urinary environment in patients with recurrent calcium nephrolithiasis has been reported to be supersaturated with respect to brushite ; in these people the induction time for nucleation of dcpd is relatively low . the nucleation and crystal growth of dcpd will decrease the calcium concentration in urine and as a result decrease the supersaturation with respect to com . thus , the direct formation of dcpd in vivo will suppress the nucleation and growth of com , which is in conflict with early thinking of dcpd promoting the formation of calcium oxalate stones by heterogeneous nucleation . recent investigations have indicated that amorphous cluster aggregation is a key step in slow biomineralization processes . in a slightly supersaturated ca p solution , stable amorphous ca p ( acp ) complexes can form spontaneously with a small thermodynamic barrier and then coagulate into large amorphous aggregates in the early induction period . p complexes via a solid solid nucleation process . with the small supersaturation in urine , hap nuclei are difficult to form directly ( induction time of more than 1 week ) ; the amorphous cap complexes could be stable for appreciable times . many studies indicated that amorphous precursors are also involved in calcium oxalate nucleation processes . p phases in the hap nucleation , the influence of acp on com formation has been ignored . the existence of amorphous calcium phosphate complexes and their coaggregation with amorphous calcium oxalate may be a key initial step in the mechanism leading to the formation of calcium oxalate ( caox ) stones . in the present study , we systematically investigated the role of phosphate on the nucleation of com using a sensitive constant composition ( scc ) method that utilizes potentiometric glass electrode and calcium selective electrode monitoring of the calcium ion and hydrogen ion activities ( 0.001 ph resolution ) associated with the nucleation events . this method allows the simultaneous monitoring of the species association and complexation in solution , as well as the nucleation and crystal growth of com . the analysis was augmented by our scanning electron microscopy ( sem ) and transmission electron microscopy ( tem ) studies performed in parallel . the results unequivocally show that the presence of amorphous calcium phosphate complexes promotes the aggregation of amorphous caox precursors , inducing the nucleation of com crystallites , and the subsequent formation of multicrystal aggregates . titrant solutions are added to maintain constant reaction solution concentrations during the experiments . a potentiometer is used to control titrant addition from stepper - motor - driven burets . reaction initiation triggered , potentiometrically , the addition of titrant solutions , which have concentrations calculated based upon the speciation computations using mass balance and electroneutrality expression together with the extended debye hckel equation . the double constant composition method ( dcc ) ( two cc devices incorporating two different ion selective sensors ) is used to simultaneously control two competing crystallization processes at constant driving force . for this study , com and brushite labeled as ba and bc , respectively , share a common b ion ( calcium ) . for the simultaneous growth of ba and bc crystals , b ion ( calcium ion specific electrode ) and c ion ( ph electrode ) selective electrodes com ( ba ) phase / controlled by calcium electrode : titrant buret no . 1 titrant buret no . 2 brushite ( bc ) phase / controlled by glass electrode : titrant buret no . 1 titrant buret no . 2 where w and t are the total concentrations in the reaction solutions and titrants , respectively , and ceff , com and ceff , brushite are the effective titrant concentrations with respect to com and brushite , respectively . calcium chloride dihydrate ( cacl22h2o ) was purchased from omnipur ( purity 99.0% , lot no . g07000246a ) and potassium dihydrogen phosphate ( kh2po4 ) was purchased from j.t . baker ( purity 99.7% , lot no . other chemical reagents were of analytical grade and purchased from j.t . baker . solutions used in this study were prepared fresh , and filtered twice through 50 nm pore size filters ( sterlitech , lot no the concentration of calcium stock solution was determined by edta titration . in this study , com nucleation experiments were made at ph 6.5 at 37.0 0.1 c in magnetically stirred double - walled 250 ml pyrex vessels at values of the relative supersaturation with respect to com ( com ) of 0.745 and 1.02 . the relative supersaturation , , and supersaturation ratio , s , are given by eq 1:1where v is the number of ions in a formula unit of com , and iap and ksp are the ionic activity and thermodynamic solubility products ( ksp = 2.47 10 m at 37.0 c ) , respectively . supersaturated reaction solutions were prepared by the slow mixing of sodium chloride ( nacl ) , potassium dihydrogen phosphate ( kh2po4 ) , potassium oxalate ( k2ox ) , potassium hydroxide ( koh ) , and calcium chloride ( cacl2 ) stock solutions ( [ ca ] = 0.045 m ) . co2 was completely removed by pumping pure , presaturated , n2 gas ( > 2 h ) into both reaction solutions and calcium chloride stock solution prior to mixing . the ph and calcium ion concentration were monitored during crystallization experiments , with a ph electrode ( orion 91 - 01 0.1 mv ) and calcium ion selective electrode ( orion 93 - 20 0.1 mv ) coupled with a single - junction ag / agcl reference electrode ( orion 90 - 01 ) . precipitates were collected from the solution by filtration during the experiments , and samples were dried and sputter - coated with graphite under vacuum before examination by field - emission scanning electron microscopy ( sem ; hitachi su-70 ) at 20 kev . transmission electron microscopy ( tem ) investigations of nucleated particles removed at various time intervals were carried out using a jeol-2010 tem at an accelerating voltage of 200 kv . recently developed scc techniques were combined with sem and tem to investigate the effect of phosphate on com nucleation . this technique was used to investigate com homogeneous nucleation ; experiments were performed at a constant supersaturation with respect to com ( com ) of 0.745 at ph 6.5 and with 0.15 m ionic strength , at 37 c . cc crystallization plots in a mixed solution of calcium oxalate ( com = 0.745 ) with and without phosphate at initial ph 6.5 , ionic strength 0.15 m. ( a ) volume of titrant addition plotted against time in control experiments ( [ ca ] = [ ox ] = 3.5 10 m , without phosphate ) . ( b ) calcium concentration change in free drift nucleation system ( [ ca ] = [ ox ] = 3.5 10 m , without phosphate ) . ( c ) titrant addition curve for phosphate containing system ( [ p ] = 8.0 10 m , [ ca ] = [ ox ] = 3.81 10 m , dcpd = 0.42 , and hap = 2.76 ) . ( d ) ph and calcium concentration changes for phosphate containing system ( [ p ] = 8.0 10 m , [ ca ] = [ ox ] = 3.81 10 m , dcpd = 0.42 , and hap = 2.76 ) . in the presence of phosphate , even the solution is undersaturated with respect to dcpd , and the nucleation of com was strongly promoted by shortening the induction time from 1150 to 590 min . the events of calcium oxalate nucleation were monitored by a calcium selective electrode , in a free drift nucleation experiment ( no titrant added ) ; the calcium concentration slowly increased throughout the induction time . this indicates the release of free calcium ions into solution at this point in the nucleation process ; after this small detectable release of the calcium , the concentration decreases as com nuclei form and crystal growth occurs ( figure 1b ) . constant composition reactions were also carried out . in the presence of phosphate com nucleated in approximately half the time as reactions without phosphate ( figure 1a , c ) . the addition of phosphate to these reactions at relatively low concentrations ( [ p ] = 8.00 10 m , [ ca ] = [ ox ] = 3.81 10 m ) , concentrations undersaturated with respect to the formation of dcpd ( dcpd = 0.412 ) , decreased the induction time for com nucleation by nearly half to 590 min under ( figure 1c ) . the rate of titrant addition in scc reactions was based on the potential change of the calcium selective electrode . when the results of the reactions in the presence of phosphate are compared with the control ( figure 1c and 1a ) , it is clear the rate of titrant addition in com nucleation reactions in the presence of phosphate ( 0.57 ml / h ) was considerably less than that of the control system ( 6.6 ml / h ) . this decrease indicates that com crystal growth is retarded in the presence of phosphate . at phosphate concentrations undersaturated with respect to the formation of dcpd , the calcium concentration slowly increased during the initial stages of the com induction period . at the same time , the ph decreased in the induction period ( figure 1d ) ; this increase is likely related to the formation of amorphous calcium phosphate as previously described by nancollas et.al . at higher phosphate concentration ( [ p ] = 3.71 10 m , [ ca ] = [ ox ] = 4.71 10 m ) , conditions supersaturated with respect to dcpd ( dcpd = 0.10 ) , the induction time was greatly reduced to only 60 min . the formation of dcpd crystals was detected , promoting com nucleation and decreasing the induction time for com formation to 60 min from 1150 min in reactions without phosphate ( figure 2 ) . double constant composition plots for com nucleation ( com = 0.745 ) in the presence of higher amount of phosphate ( [ p ] = 3.71 10 m , [ ca ] = [ ox ] = 4.71 10 m ) at ph 6.5 , ionic strength 0.15 m. solution is supersaturated with respect to dcpd ( dcpd = 0.10 ) and hap ( hap = 4.41 ) . in addition to scc experiments , com free drift nucleation experiments were carried out to further investigate the effect of phosphate on the nucleation of com . the free drift nucleation experiments were done at a higher supersaturation with respect to calcium oxalate formation which decreased the induction time ( com = 1.02 ) at ph 6.5 . these experiments were initiated by the addition of calcium solution to the reaction solution . the presence of phosphate in the reaction solution ( [ p ] = 3.0 10 m ) at concentrations undersaturated with respect to dcpd ( dcpd = 0.6 ) resulted in a rapid increase in ph followed by a slower decrease ( figure 3 , stage i ) . in the co2 free system , the ph change is a result of the varying equilibria of phosphate and oxalate species . a similar discussion in our previous work regarding the relatively slower dehydration rate of calcium ions compared to that of phosphate ions suggests the final addition of calcium to the reaction solution resulted in the calcium - deficient cluster formation . these clusters are not stable : the rapid release of excess hpo4 results in a sharp increase in ph following calcium addition . as this occurs , calcium ions associate with the hpo4 which results in the observed decrease in calcium concentration at this stage . the initial ph and calcium concentration changes confirmed the formation of amorphous calcium phosphate cluster in the calcium oxalate nucleation system . at the same time , calcium oxalate complex formation also contributed to the decrease in calcium concentration observed during this stage ( figure 3 , stage i ) . following stage i the ph decreased slightly and the calcium concentration increased ( figure 3 , stage ii ) ; this corresponds to the formation of com at this point in the induction period . the induction time or com nucleation at com = 1.02 in the presence of phosphate ( [ p ] = 3.0 10 m ) was 130 min , decreased from 430 min in control experiments ( supporting information , figure s2 ) ; these conditions are undersaturated in dcpd . at stage iii , the calcium concentration and ph remain constant ; this is likely related to a solid phase transition from calcium oxalate precursors to calcium oxalate prenuclei . following the 120 min stabilization in ph and calcium concentration , the calcium concentration decreased . this is the start of stage iv , which is associated with the com crystal growth ( figure 3 , stage iv ) . calcium and ph changes during nucleation of calcium oxalate ( com = 1.02 ) in the presence of phosphate ( [ p ] = 3.0 10 m , [ ca ] = [ ox ] = 4.74 10 m , dcpd = 0.60 , and hap = 2.045 ) at ph 6.5 , ionic strength 0.15 m. the inset highlights the decrease in calcium concentration during the first 20 min of the reaction . the precipitates were harvested at various time intervals and investigated by high - resolution transmission electron microscopy ( tem ) , selected area electron diffraction ( saed ) , and scanning electron microscopy ( sem ) . in the absence of phosphate large aggregates up to 100 nm were detected , in addition to smaller ca ox particles with size less than 5 nm diameter . the slow addition of calcium solution for about 60 min ( figure 4a ) , followed by aging for 250 min , produced some larger aggregates ( up to 500 nm ) with porous features . the largest porous aggregates formed ( larger than 1000 nm ) 1000 min after the addition of calcium to the reaction solution ; at the same time some denser aggregates with crystal - like shape were detected ( figure 4c ) . after the induction time ( 1200 min , figure 4d ) , small crystal nuclei were observed by tem and the previous large porous amorphous aggregates were not detected by saed . this would indicate that the large amorphous ca ox aggregates dissolved after nuclei formation and crystal growth . these findings are supported by the dissolution reprecipitation and solution - mediated transformation mechanisms . the tem results showed that the com nucleation took place via an amorphous phase pathway , in which large porous amorphous particles were first formed by aggregation of small ca ox clusters in the induction time , and then the denser nuclei formed and induced the desolation of amorphous precursors . phase and morphology evolution of calcium oxalate precipitates during the induction periods in the absence of phosphate with supersaturation of com = 0.745 at initial ph 6.5 and ionic strength 0.15 m. ( a d ) tem micrographs and saed pattern of precipitates at the induction period ; ( e ) sem micrograph of com crystal at end of experiment . scale bar : ( a ) 20 , ( b ) 50 , ( c ) 100 , ( d ) 50 , and ( e ) 400 nm . sem micrographs depicting the morphology evolution of calcium oxalate precipitates during the induction period in the presence of phosphate ( [ p ] = 8.0 10 m , [ ca ] = [ ox ] = 3.81 10 m , dcpd = 0.42 , and hap = 2.76 ) with supersaturation degree of com = 0.745 at initial ph 6.5 and ionic strength 0.15 m. the induction time was 590 min . after the slow ( 5 min ) addition of calcium solution to the reaction solution , separated particles about 30 nm in size were detected ( figure 5a ) . at 250 min after the addition of calcium large aggregates were formed . the ca / p ratio detected by energy dispersive x - ray spectroscopy of these aggregates was ca / p 3.6 ( figure 5b ) ; this relatively high ca / p ratio suggests the formation of coaggregates of acp and ca ox complexes early in the induction periods . at 500 min ( induction time was 590 min ) , larger aggregates ( over 2 m ) formed , which contained nuclei of com ( figure 5c ) . after 1600 min plate - like com crystal aggregates formed ( figure 5d ) . ox clusters ( less than 5 nm ) surrounding the large amorphous calcium phosphate complex spheres ( about 60 nm ) after the addition of calcium to the reaction solution ( figure 6a ) ; 60 min after the addition of the calcium solution , larger aggregates of acp spheres were observed and these formed larger coaggregates ( figure 6b ) . high energy electron bombardment during tem caused the adsorbed caox clusters on the surface of acp spheres to became larger . these results indicated that the existence of acp promoted the aggregation of small ca ox clusters on the surface , an important step to control nucleation of com . tem micrographs and saed pattern of aggregates between large amorphous calcium phosphate and smaller peripheral amorphous ca ox precursors at early induction period of com nucleation in the presence of phosphate ( 8.0 10 m ) with undersaturated dcpd ( dcpd = 0.42 ) . this work has demonstrated that , in the presence of phosphate , even in undersaturated solutions with respect to ca this work further demonstrates that the com nuclei form via amorphous ca ox precursor clusters , which coaggregate with acp to form large amorphous particles before nucleus formation in the presence of phosphate . in a supersaturated solution of calcium oxalate , many ca speciation calculations indicate that there are mainly two calcium oxalate species , the uncharged [ caox ] complex and the positive [ ca2ox ] complex ( table 1 ) , and of the two the former predominated . kinetic effects due to the faster dehydration rate of ox when compared with calcium , the ox - deficient species , [ ca2oxh2o ] , result in the formation of these species which transform to the thermodynamically more stable [ caox ] complex following the release of extra calcium ions . this was observed as a slow increase of calcium concentration during the induction period . in the absence of phosphate , these ca ox complexes will aggregate to small particles of com which induce the formation of com nuclei . previous studies on hydroxyapatite nucleation have shown that a relatively stable amorphous cluster with the composition of [ ca-(hpo4)1+xnh2o ] forms initially in ca these amorphous clusters self - assemble to large acp - i phases early in the induction period of hap nucleation . in the presence of phosphate , the existence of negative ca p complexes , [ ca-(hpo4)1+xnh2o ] , will promote the aggregation of positive ca ox clusters , [ ca2oxh2o ] by electrostatic attraction and form the acp aco coaggregating structure as shown in tem images . at the same time , some calcium ions released from slow condensation of [ ca2oxh2o ] clusters will complex with more hpo4 and induce a further hydrolysis of h2po4 , resulting in a slow ph decrease during the induction period . the coaggregation effect from acp promotes the formation of large calcium oxalate complexes , which promote the formation of com prenuclei increasing to their critical size , and forming stable nuclei . the numerous ca ox clusters aggregating around the acp sphere provide multiple sites for the following nucleation and growth , resulting in multiple com crystals encapsulating the calcium phosphate phase . the agglomerate structure of multiple com crystals aggregating around the calcium phosphate phase results in a simulated kidney stone which is too large to pass the urinary tract . based on the above results , a new mechanism for calcium renal stone formation has been proposed ( figure 7 ) . an amorphous calcium oxalate ( aco ) cluster containing phosphate is formed , driven by the electrostatic interaction of acp and aco . the result is an amorphous coaggregate with aco surrounding an acp sphere ( figure 7a ) . the aco clusters self - assemble to larger size aco particles on the acp surface ( figure 7b , process i ) . the numerous large aco particles provide the ideal site for com prenuclei formation during the process of aco phase condensation ( figure 7c , process ii ) . as the size of prenuclei reaches a critical size , the com nuclei will stabilize and induce the crystal growth ( process iii ) . multiple nuclei grow on the acp surface and finally form a structure of numerous com crystals encapsulating an acp sphere ( figure 7d ) . due to the coaggregating structure , the size of the whole agglomerate quickly increases , making it difficult to expel from the body , and a renal stone has formed . p crystal , such as dcpd or hap , via a slow confined solid phase transition process ( figure 7e , process iv ) . the coaggregation of the amorphous precursors acp and aco , followed by the nucleation of com surrounding a large acp cluster , provides a possible initial step in the mechanism leading to the formation of renal stones . schematic illustration of the nucleation mechanism for com in the presence of phosphate at biological conditions . ox clusters aggregate around large acp spheres early in the induction period , ( b ) acp surface promotes aco aggregation , ( c ) multiple prenuclei form within aco clusters , ( d ) a composite of multiple com crystals forms , and ( e ) a kidney stone containing ca the new mechanism of stone formation via coaggregation of amorphous precursors is relevant to the current investigation of the mechanism of nephrolithiasis and is an interesting comparison with the previous mechanism of heterogeneous nucleation induced by dcpd . the condition for dcpd supersaturation is unlikely in urine , which needs a relatively high calcium or phosphate concentration in the acidic urine environment . however , the formation and growth of dcpd will consume the calcium ion and decrease the supersaturation level of com . the new physicochemical mechanism for kidney stone formation highlights the important role of phosphate , and the formation of calcium phosphate nidus . modern renal stone treatment involving proteins , amino acids , and organic crystal - growth inhibitors such as citric acid typically ignore the side effects of promoting amorphous precursor aggregation . in solutions that are supersaturated with respect to calcium oxalate , the presence of phosphate results in the initial formation of amorphous calcium phosphate clusters . these clusters were found to promote the aggregation of amorphous calcium oxalate complexes which induce the nucleation and growth of urinary stones . these revelations both expand our knowledge of urinary stone development and provide potential targets for treating the condition at the molecular level . we expect that the results will inspire novel approaches to our understanding of kidney stone formation mechanisms , which will lead to innovative therapeutic interventions to improve the health of patients with kidney diseases .
the majority of human kidney stones are comprised of multiple calcium oxalate monohydrate ( com ) crystals encasing a calcium phosphate nucleus . the physiochemical mechanism of nephrolithiasis has not been well determined on the molecular level ; this is crucial to the control and prevention of renal stone formation . this work investigates the role of phosphate ions on the formation of calcium oxalate stones ; recent work has identified amorphous calcium phosphate ( acp ) as a rapidly forming initial precursor to the formation of calcium phosphate minerals in vivo . the effect of phosphate on the nucleation of com has been investigated using the constant composition ( cc ) method in combination with scanning electron microscopy ( sem ) and transmission electron microscopy ( tem ) . our findings indicate com nucleation is strongly promoted by the presence of phosphate ; this occurs at relatively low phosphate concentrations , undersaturated with respect to brushite ( dicalcium phosphate dehydrate , dcpd ) formation . the results show that acp plays a crucial role in the nucleation of calcium oxalate stones by promoting the aggregation of amorphous calcium oxalate ( aco ) precursors at early induction times . the coaggregations of acp and aco precursors induce the multiple - point nucleation of com . these novel findings expand our knowledge of urinary stone development , providing potential targets for treating the condition at the molecular level .
hepatocyte growth factor ( hgf ) , located chromosome 7q21.1 , is also known as interleukin ( il)32b , scatter factor , hepatopoietin a , lung fibroblast - derived mitogen or fibroblast - derived tumour cytotoxic factor , mainly from epithelial origin cells . hgf binds to its receptor c - met , acts as a multi - functional cytokine and regulates cell growth , motility and morphogenesis by activating a tyrosine kinase signalling cascade . the extracellular domain of c - met comprises a large seven - bladed fl - propeller ( sema domain ) , a small cysteine rich domain and four immunoglobulin - like domains ( ig1ig4 ) , of which the c - met sema and cysteine rich domains bind one domain of hgf . hgf is secreted as a single inactive polypeptide and belongs to the plasminogen subfamily of s1 peptidases without the detectable protease activity . it is cleaved by serine proteases into a 69-kd -chain and 34-kd -chain and becomes an active , heterodimeric molecule with the disulfide bond between the and chains . the activation of the hgf / c - met signal pathway stimulates mitogenesis , cell motility and matrix invasion . the present paper is to overview the potential role of the hgf / c - met signal pathway in the development and metastasis of lung cancer , divert inhibitions of the hgf / c - met signal , mechanisms of hgf / c - met involvement in the metastasis by stimulating the production of vascular endothelial growth factor ( vegf ) and activating the matrix metalloprotease ( mmp ) , and possibility to be used as an independent or combining therapeutic target . hgf has multi - functional roles in physiological and pathophysiological conditions , e.g. catalytic activity , serine - type endopeptidase activity , activation of mitogen - activated protein kinase and c - met signalling pathway , involving organ development and regulation of mesenchymal epithelial signalling . out these , the amplification and mutation of c - met associated with tumorigenesis , invasion and metastasis vary among races , e.g. rare in japanese patients with nsclc , and may predict the prognosis of patients with nsclc . hgf can be also produced by cancer cells and cancer stem cells , responsible for high tumorogenic and metastatic abilities . the hgf / c - met signal pathway could be activated in autocrine fashion and allocated in the bronchoalevolar junctions of lung tumour cells . hgf was found to promote the malignant development of cancer cells by enhancing invasion and metastasis . the bifunctional transcription factor protein ( nk4 ) , as a competitive antagonist for hgf , can inhibit tumour growth and lung metastasis demonstrated in mice after the systemic administration of a replication - defective adenovirus expressing nk4 . the effect of nk4 treatment is highly dependent upon the deliveries of nk4 and the intratumoural adeno - associated virus - nk4 administration had the highest therapeutic response . the treatment with nk4 significantly reduced the average metastatic burden , rather than the tumour size and average numbers of macroscopic lung metastases . experimental evidence showed that hgf could facilitate the adhesion of colon cancer cells to endothelial cells in a dose - dependent manner , while nk4 and anti - hgf antibody could reduce hgf - induced interaction between two cells and phosphorylation of focal adhesion kinase , a downstream of integrin signalling . stable nk4 expression was associated with decreased number of pulmonary metastatic foci , which could be increased by hgf . this indicates that hgf / c - met signalling is involved in the process of haematogenous pulmonary metastasis . there was still a lack of direct evidence to show the specificity of nk4 to the lung cancer and c - met receptor , since nk4 d is a non - specific antagonist against hgf . for example , nk4 has an additional anti - angiogenic effect independent of its hgf - antagonist function . it is also questionable whether the hgf / c - met signal plays the role in metastasis of the cancer to the lung and has the specificity in the lung cancer , since a wide variety of human malignancies exhibit sustained c - met stimulation , overexpression , or mutation , including carcinomas of the colon , stomach , bladder , breast , ovarian , pancreas , kidney , liver , lung , head and neck , thyroid , and prostate , sarcomas , haematological malignancies , melanoma and central nervous system tumours [ 9 , 10 ] . a number of c - met pathway antagonists with potential clinical applications are involved in the main approaches , including antagonism of ligand / receptor interaction , inhibition of the tyrosine kinase catalytic activity and blockade of the receptor / effector interaction . the inhibition of hgf / c - met interaction with a single monoclonal antibody could prevent tobacco carcinogen - induced high number of tumours per mouse and tumour proliferative index , low apoptosis and overexpression of phosphorylated mitogen - activated protein kinase expression in some animals . however , administration of hgf monoantibody showed little or no effects on some animals whose tumours contained mutant k - ras , an alternative downstream signalling pathway with probably competitive role of hgf / c - met pathway . conversely , other studies to inhibit c - met in mice and cultured cells by genetic and pharmacological approaches demonstrated that the premalignant lung lesions progressed to multifocal lung adenocarcinomas owing to somatic mutations in k - ras . in such condition , overexpression of c - met and high concentrations of hgf could be detected in bronchoalveolar lavage fluid and prevented by the c - met inhibitor . it indicates that c - met may play a critical role in the development of mutant k - ras - dependent lung cancer . in addition to those main approaches , there may be more inhibitory ways of hgf / c - met signal to be considered . for example , rapid growth of cancer cells often creates insufficient supply of oxygen and nutrients in the tumour nest . hypoxia was found to up - regulate the expression of hgf and il-8 responsible for cancer cell metastasis in lung adenocarcinoma , probably through the activation of prostaglandin f(2 ) . the ccl3-ccr5 axis signal was suggested to regulate hgf expression to accelerate neovascularization and subsequent metastasis formation probably through the production of vegf . the activation of the hgf / met signal has been shown to induce the development and angiogenesis of lung cancer , probably by stimulating the production of vegf . the adaptor protein shc was suggested as the proximal signalling proteins responsible for c - met - induced vegf expression , since c - met failed to induce vegf production in the shc - deficient condition . vegf could induce shc recruitment to the kinases using mutants of the /erbb2 receptor tyrosine kinase ( rtk ) , where the mutant - bound shc induced vegf production . shc was essential for the induction of vegf production by the c - met / hgf rtk oncoprotein and serum - derived growth factors . it implies that shc acts as a critical angiogenic switch for vegf production downstream from the c - met and erbb2 rtks . experimental findings demonstrated that c - met was involved in tumorigenesis and liver metastasis by regulating the src activation , since the down - regulation of c - met could reduce src activity and activation of erk1/2 and akt , followed by a decreased vegf production , tumour size and incidence , and vessel formation in tumours . the inhibition of src could reduce basal vegf production , proliferation , migration and anchorage - independent growth , which could be rescued by hgf . such dose - dependent inhibitory effects on src also reduced hgf - induced migration of tumours rather than hgf - induced anchorage - independent growth . hgf binds and activates c - met through an autocrine signalling and an essential transcription factor for angiogenesis , ets-1 , stimulating the matrix - degrading pathway such as the production of mmp-1 . growth factors secreted by either host or tumour cells play a major role in cell progression , by stimulating cell division and migration and modulating mmp production which are involved in the process of the invasion and metastasis . growth factors could up - regulate the expression and activity of mmp-9 and mmp-2 in nsclc cells where hgf and epidermal growth factor ( egf ) could stimulate the conversion of mmp-9 from a latent to an active form . intrapulmonary levels of mmp-9 and hgf were found simultaneously higher during cancer metastasis to the lung , although the mechanism by which hgf modulates the activity of mmps remains unclear . it is possible that mobilized cancer to the lung has higher expression of hgf and c - met as a signal axis to increase the secretion of mmp-9 and the expression of membrane type 1-mmp and facilitate cell migration like granulocyte colony - stimulating factor induced mobilization of haematopoietic stem / progenitor cells . it is also possible that hgf induces the production and activity of mmp-2 , accompanied with transforming growth factor ( tgf) , fibronectin and urokinase type pa involved in junction dynamics , regulating the tight junctions by altering the synthesis of occludins and creating the proper microenvironment for tumour cell metastasis within the lung tissue like leydig cells [ 21 , 22 ] . recent evidence demonstrated that hgf / c - met activation could deregulate cadherin - based cell - cell adhesions , decrease the expression of cytokeratins and increase activity of mmp-2 during tumorigenesis and metastasis in premalignant and malignant ( metastatic ) cells . such hgf / c - met axis activation could be balanced by the auto - secretion of an approximately 55 kd hgf fragment which was produced during the carcinoma progression and had a negatively regulatory effect on hgf signalling . another possibility is that other factors like tgf-1 may up - regulate c - met expression and activity and hgf production in the lung , resulting in increased activities of mmp-2 and mmp-9 through focal adhesion kinase phosphorylation , like in lung fibrosis . further studies on the mechanisms of constitutive activation of c - met in lung adenocarcinoma cells demonstrated that c - met amplification may play a more critical role than mutations in the sema domain or any part of the cytoplasmic domain of c - met . the constitutive activation of c - met could be associated with c - met overexpression with or without gene amplification in the largely ligand - independent and cell - matrix adhesion - dependent pattern . the c - met and epidermal growth factor receptor ( egfr ) are potential targets of combination therapy for the cancer due to a wide expression on cancer cells during the development and progression of cancer . egfr inhibitor has been used as a target therapy for nsclc , of which about 80% highly expressed c - met . co - immunoprecipitates of c - met and egfr were seen in protein extracts from tumour cells rather than normal cells . cross - talk between the tgfa / egfr and the hgf / c - met pathways might induce mitogenic or motogenic signal amplification and cell growth in the unidirectional way ( fig . signalling pathways c - met activation may initiate the transcription - dependent egfr activation to carry out hgf - induced cell proliferation and motility , which was proposed to be egfr dependent and/or through amphiregulin and heparin - binding egf - like growth factor [ 28 , 29 ] . the mechanism by which hgf induced migration of human lung cancer cells was proposed to be that akt phosphorylation of hgf signalling inhibited the activity of phosphoinositide 3-kinase ( pi3k ) , without affecting phosphorylation of met and erk . furthermore , it was demonstrated that hgf could induce egfr inhibitor resistance of lung adenocarcinoma cells with egfr - activating mutations by restoring the pi3k / akt signalling pathway via phosphorylation of c - met . the inhibition of c - met by sirna rather than egfr or erbb3 could reverse hgf - induced egfr inhibitor resistance and phosphorylation of akt . in lung cancer patients with intrinsic or acquired resistance to egfr inhibitor , the immunoreactivity for hgf became stronger in cancer cells harbouring egfr - activating mutations but no t790 m mutation or met amplification , a novel mechanism of egfr inhibitor resistance and a considerable strategy for more successful treatment with egfr inhibitors . tgfa / egfr signal pathway may directly or indirectly lead to c - met , while hgf / c - met does not affect the phosphorylation of egfr . tgfa / egfr signal was proposed to activate the phosphorylation of c - met , transcription factor erk1 , cytoskeletal reorganization factor eps8 and adhesion factor ctnnb , while hgf / c - met could activate the phosphorylation of endocytotic factor anxa1 , adaptor protein gab1 and adhesion factors ctnnb and shp2 . both tgfa / egfr and hfg / c - met signal pathways can directly activate ctnnb and indirectly activate the transcription factor atk through the binding with her3 or gab1 . however , the role of tgfa / egfr - induced secondary phosphorylation of c - met in the egfr - dependent tumour growth remains questionable , since only a very small fraction of c - met is phosphorylated by tgfa . recently , gao et al . applied the global phosphoproteomic method to identify phosphotyrosine signalling downstream of egfr and c - met . amplified c - met drives the activity of egfr family members and mutated and amplified egfr can also drive c - met activity . when comparing the signalling networks in egfr - dependent and c - met - dependent cells , about 50 proteins were considered as the key factors to participate in pathways and mediate the response to drugs . tgfa / egfr signal was proposed to activate the phophorylation of c - met , transcription factor erk1 , cytoskeletal reorganization factor eps8 and adhesion factor ctnnb , while hgf / c - met could activate the phosphorylation of endocytotic factor anxa1 , adaptor protein gab1 as well as adhesion factors ctnnb and shp2 . both tgfa / egfr and hgf / c - met signal pathways can directly activate ctnnb and indirectly activate the transcription factor atk through the binding with her3 or gab1 ( fig . 1 ) . it was proposed that c - met might activate the egfr agonist tgf through tumour suppressor phosphatase and tensin homolog . in the cross - talk between tgfa / egfr and hgf / c - met signal pathways , the tgfa / egfr signal pathway seems to play more dominate role and gain more scientific attention , most likely because the number of direct binding and indirect interaction factors of egfr is more than c - met . there are about five to six more direct binding proteins with egfr , e.g. adhesion protein shp2 , transcription factors stat5 and 6 , proliferation factor plcg1 , adaptor factor mig6 and gab1 , as shown in fig . 2 . however , results from the study on the signalling networks between oncogenic egfr and c - met indicate that hgf / c - met might have more indirect interaction with egfr . nsclc cell lines with the expression of both c - met and egfr ( e.g. a549 , h1838 , h2170 , sw900 , sw1573 , h358 , sklu-1 and h1993 ) had different sensibilities and responses to their ligands and inhibitors , associated with combining doses , rationales and durations . for example , egf and hgf at 100 ng / ml showed a synergistic effect on a549 , h1838 and skmes cell proliferation at 4872 hrs . hgf ( 40 ng / ml ) and egf ( 5 ng / ml ) induced synergistic phosphorylation of c - met ( tyr 1003/1230/1234/1235 ) . egf and hgf at 100 ng / ml for 2 hrs had an additive effect on he induction of cell motility ( especially membrane ruffling ) in h1993 cells . the combination of c - met tyrosine kinase inhibitor su11274 ( 2 mm ) and egfr tyrosine kinase inhibitors tyrphostin ag1478 ( 0.5 mm ) had a synergistic effect on inhibition of cell proliferation ( 65% ) , while egfr inhibitor ( gefitinib , iressa ) and c - met inhibitor ( su11274 ) had a synergistic effect on apoptosis . those data indicate that there may be other factors contributing to the sensitivity and activation of c - met and egfr in addition to the cross - talking between egfr and c - met . the number of direct binding and indirect interaction factors of egfr is more than c - met in the cross - talk between tgfa / egfr and hgf / c - met signal pathways . there are about five to six more direct binding proteins with egfr , e.g. adhesion protein shp2 , transcription factors stat5 and 6 , proliferation factor plcg1 , adaptor factor mig6 and gab1 . hgf / c - met is considered to be one of the candidates responsible for the development of egfr inhibitor resistance in the therapy for nsclc , since both are a family of oncogenes and regulate important cellular processes . amplification of c - met caused gefitinib resistance by driving erbb3 ( her3)-dependent activation of pi3k in nsclc , a pathway specific to egfr / erbb family receptors . c - met signalling may play a key role in lung cancer oncogenic signalling and interface with egfr , which may be an alternative co - therapy for egfri resistance nsclc ( fig . 3 ) . c - met amplification occurred independently of egfrt790 m mutations , indicating that c - met may be a clinically relevant therapeutic target for some patients with acquired resistance to egfr inhibitors . experimental results demonstrated that both met and egfr were expressed in the egfri - resistant lung cancer cell line h1975 ( l858r / t790m - mutant egfr ) and c - met signalling had egfr - inhibitor - resistant role in lung cancer . the hgf / c - met signal path was functional and activated in egfr - inhibitor - resistant cells with the oncogenic mutant egfr ( l858r / t790 m ) signal axis . it was demonstrated that dual treatment using a c - met inhibitor plus a reversible or irreversible egfr kinase inhibitor had more significant inhibitory effects , as an alternative strategy to circumvent t790m - egfr - mediated resistance in lung cancer . the potential mechanism of the hgf/ c - met signal pathway hallmarks in lung cancer . both hgf and tgfa can activate pi3k and mark signal pathways directly and indirectly through the k - ras , leading to the production of hgf , vegf and mmps and regulating cell proliferation , invasion and metastasis in nsclc . the clinical study showed the most of patients ( 7/9 ) with egfr - inhibitor - resistant tumours had a secondary t790 m mutation , while the expression of hgf and c - met was only observed in egfr - inhibitor - resistant tumours when t790 m mutation existed . it seems that the hgf / c - met signal may play a partial or assistant role in the development of egfr - inhibitor - resistance . there is also possibility that c - met phosphorylation may play more important role than its overexpression . c - met may be indirectly involved e.g. by the binding of the invasion protein of listeria monocytogenes , a gram - positive , facultative intracellular human pathogen . the c - met can be activated when the capped leucine - rich repeat domain of the invasion protein interacts with the high affinity met - binding site , followed by an additional activation of inter - repeat region , an immunoglobulin ( ig ) like moiety . without the third party , hgf was found to suppress apoptosis - inducing factor expression and increase resistance of non - specific chemotherapy drugs for nsclc , e.g. cisplatin , through c - met and its downstream effector , focal adhesion kinase . flavonoids ( apigenin ) could inhibit hgf - induced cancer cell motility , scattering , migration and invasion in a dose - dependent manner through down - regulation of akt phosphorylation rather than c - met , erk and jnk phosphorylation . such non - specific compounds inhibited the hgf - induced clustering and function of 4 integrin at actin - rich adhesive site and lamellipodia , including cell - matrix adhesion and cell - endothelial cells adhesion through pi3k - dependent manner . in conclusion , there is growing evidence that the hgf / c - met signal play an important role in the development of nsclc , although the specificity of such role needs to be clarified . it seems clear that the hgf / c - met signal contributes to the metastasis of cancer cells to the lung by stimulating the hyperproduction and overactivation of cytokines and enzymes , e.g. hgf , vegf and mmps . although the mechanism of interaction between hgf / c - met and tgfa / egfr remains unclear , the cross - talk and balance between those two signal pathways are critical and necessary in the development of new therapies for nsclc . there are great needs to investigate the combining strategy of c - met and egfr inhibitors , therapeutic efficacy and rational of their combination and optimal delivery of drugs . it is to be clarified whether c - met inhibitors can be applied as the backup if egfr inhibitors fail or both should be simultaneously used as a personalized medicine .
abstractthere is growing evidence that the signal pathway between hepatocyte growth factor ( hgf ) and its receptor c - met plays an important role in the development of lung cancer , although the specificity of such role is to be clarified . it seems clear that the hgf / c - met signal contributes to the metastasis of cancer cells to the lung by stimulating the hyperproduction and overactivation of cytokines and enzymes , e.g. hgf , vascular endothelial growth factor and matrix metalloproteases . the hgf / c - met signal may act as the candidate responsible for the development of epidermal growth factor receptor ( egfr ) kinase inhibitor resistance . experimental evidence showed that the combination of both egfr and c - met inhibitors had synergetic or additive therapeutic effects on lung cancer . although the mechanism of interaction between hgf / c - met and transforming growth factor - a / egfr remains unclear , the cross - talk and balance between those two signal pathways are critical and necessary in the development of new therapies for lung cancer .
definition of an infrared photometric system was begun by johnson and colleagues ( cf . johnson , 1966 ) . at that time the @xmath3 and @xmath4 bands were rather arbitrarily defined by quite broad filters centered at around 3.5@xmath5 m and 4.8@xmath5 m . observations at @xmath3 employed as detectors pbs cells , the long wave sensitivity limits of which defined the edge of the band , and at @xmath4 much less sensitive , broadband , bolometers or pbse cells were used . early infrared filters were often single remnants of manufacturers batches and hence systems were not reproducible . in addition , early infrared filter bandpasses were not well matched to the atmospheric windows , and many absorption features , especially of water , were included . as a consequence the exact bandpass applicable to any given observation depended on the atmospheric water content , and observations were not consistent between different sites or , indeed , at the same site at different times . the introduction of insb detector technology made it possible to establish a new band , centred at 3.8@xmath5 m somewhat redwards of the @xmath3 band which offered a much better match to the transmission of the terrestrial atmospheric window . this has became known as the @xmath0 band , and has effectively replaced the @xmath3 band , which is no longer commonly used . an excellent review of the status of the @xmath6 passbands and existing systems , as it was in the late 1980s , is given by bessell & brett ( 1988 ) . in the mid1980s , as infrared detector sensitivities continued to increase , many observatories found that the high thermal background admitted by the broadband @xmath4 filter saturated the new detectors . filters with narrower bandpasses were introduced ; these were commonly referred to as @xmath1 . although the same labels , @xmath0 and @xmath1 , were employed at various observatories , there were often significant differences between the particular filter bandpasses employed and hence between their resulting photometric systems . in the late 1990s standardization of the near infrared filter set was proposed by groups at the gemini observatories and the university of hawaii ( simons & tokunaga , 2002 ; tokunaga , simons & vacca , 2002 ) . this has been largely achieved by the design of bandpasses which are much less sensitive to varying water vapour conditions , and the organization of a large consortium purchase of these filters . these filters are now known as the mauna kea observatories near infrared ( mko nir ) filter set . note , however , that they are specifically designed to allow accurate photometry to be performed , and intercompared , at a range of altitudes , and are not simply optimised for the mauna kea site . as telescope and detector technology has continued to improve , and fainter and cooler objects are discovered , observations in the thermal infrared have become ever more desirable astronomically . however , standard stars for the @xmath0 and @xmath4 or @xmath1 bands are still sparse and the available set inhomogeneous . over the last two years staff at the 3.8 m uk infrared telescope ( ukirt ) have therefore undertaken an observing programme to establish an enlarged and homogeneous set of photometric standards , observed with improved accuracy through the mko nir @xmath0 and @xmath1 filters , and extending to magnitudes faint enough to be accessible to modern ( small - well " ) detectors used on 810-m telescopes . this paper describes that work . a history of the @xmath3 and @xmath4 filter bandpasses , and of the standard stars employed at ukirt , is given in 2 ; the observational technique in 3 ; the results in 4 ; a discussion in 5 ; and our conclusions in 6 . the list of standard stars in the @xmath3 , @xmath0 and @xmath4 bandpasses used by observers at ukirt dates from 1992 and is in house only , having never been formally published ( although at the time of writing it is available on the observatory web pages ) . magnitudes were derived from elias et al . ( 1982 ) and sinton & tittemore ( 1984 ) supplemented by data from the _ nasa infrared telescope facility photometry manual _ ( 1986 ) . ukirt observers own observations between 1986 and 1989 were collected in 1989 by s. koyonagi and t. hawarden and used to correct the @xmath7 , @xmath8 , @xmath9 and @xmath0 values in the telescope " list . a final update based on observations in 199091 and revised transformations to the cit system was carried out by m.m . casali in 1992 . this list is known as the ukirt bright standards " . from the 1990s on , use of the @xmath3 and the broadband @xmath4 filters ceased at ukirt ; these were replaced by @xmath0 and a narrower band @xmath1 filter . observers simply adopted the broad band @xmath4 magnitudes to calibrate their narrower band @xmath1 data , since tests at the telescope had shown that there was no colour dependency between the filters , at least for spectral types earlier than k ( geballe , 1991 ) ; the presence of photospheric co absorption was expected to lead to differences between @xmath4 and @xmath1 of a few percent for later type stars . this is discussed further in 4 . ukirt s 15@xmath5 m imager ircam has a 256@xmath10256 insb detector array . in 1999 ircam was equipped with new optics , giving a smaller pixel field of view of 0@xmath1108 . at the same time it was equipped with the mko nir @xmath0 and @xmath1 filters ( simon & tokonaga , 2002 ; tokunaga et al . , figure 1 compares the previously used `` ukirt '' system @xmath0 bandpass with the mko nir filter , and also plots transmission profiles for the old broadband @xmath4 compared with the new mko nir @xmath1 . the filter cold transmission profiles are given in table 1 , together with the profile convolved with dry and wet atmospheric conditions as shown in figure 1 . the atmospheric transmission spectra were obtained from the gemini observatory web pages and were calculated by lord ( 1992 ) . nir filters were designed to match the atmospheric windows and to maximise throughput while providing better photometric performance . simons & tokunaga ( 2002 ) calculate the theoretical photometric error due to non linear extinction to be 1.4 and 5.9 millimags for the @xmath0 and @xmath1 filters , respectively , for the mauna kea site . these errors increase to 3.7 and 8.1 millimags at @xmath0 and @xmath1 for a 2 km site . to investigate the effect of changing water vapour content , we have synthesised magnitudes for the wet and dry conditions of table 1 for g5v and m7v stars . stellar theoretical infrared spectra were obtained from cohen ( 2003 , private communication ) and hauschildt , allard & baron ( 1999 ) . these calculations showed that the effect of variable water content is small : @xmath123 millimags at @xmath0 and @xmath125 millimags at @xmath1 . the filter profiles shown in figure 1 and listed in table 1 do not include other transmission effects due to telescope and instrument optics and the detector . the telescope mirrors are aluminised and light is reflected to the instrument from a silver - dielectric coated dichroic tertiary mirror . the camera has an uncoated calcium fluoride window and contains coated barium fluoride and uncoated lithium fluoride lenses . the detector is insb with an anti reflection coating . prior to installation of the mko nir filters and modification to a smaller pixel field of view , the camera had one fewer barium fluoride and lithium fluoride lens , and two additional external gold mirrors . the reflection and transmission curves of the dichroic , gold mirrors , calcium fluoride and lithium fluoride lenses are all flat within measurement error over the relevant wavelength range . the aluminised telescope mirrors have a very small change in reflectivity increasing from 98.0% at 3@xmath5 m to 98.4% at 5@xmath5 m ; the transmission of the barium fluoride lens decreases from 95.6% at 3@xmath5 m to 94.4% at 5@xmath5 m ; and the array quantum efficiency ( qe ) varies between 87.4% and 90.0% . calculations of synthetic magnitudes for a g5v and an m7v star show that these optical elements effect the derived magnitudes by less than 1 millimag . to summarise , the previous ukirt system magnitudes , and those published here , are effectively defined by the filter bandpasses and the atmospheric transmission . we note that the newer generation insb arrays , the 1024@xmath101024 aladdin arrays , have an anti reflection coating with a more structured wavelength response . our current thermal imager uses an aladdin detector and also contains barium fluoride lenses whose coating has a 5%deep feature around 3@xmath5 m . the net change to the photometric system is calculated to be @xmath121 millimag except for late type stars at @xmath0 where the difference is @xmath133 millimag . we show in 4 that the measurement errors for the primary standards presented here are typically 0@xmath2015 at @xmath0 and 0@xmath2026 at @xmath1 , therefore variations in the optical design of a 35@xmath5 m imager and telescope system are unlikely to affect the photometric system to any measurable degree . furthermore , the mko nir filters are designed to match the atmospheric windows , and appear to do so well enough that , even at a lower elevation site , the effects of variable water vapour and non linear extinction are also substantially less than the typical observational error . overall the results presented here using the mko nir filters should be generally useable to calibrate observations with conventionally designed imagers and telescopes and on most sites . ircam was used for all the observations , with the mko nir @xmath0 and @xmath1 filters . observations were made over 26 engineering nights ( or part nights ) between 1999 september and 2002 july . towards the end of this period , once most of the stars were well established , we used calibration data from visiting observers runs to supplement our own measurements . primary standard stars were selected from the final ukirt bright standards list . to avoid saturation , the stars were chosen from amongst the fainter objects on the list , with @xmath14 and @xmath15 . in addition we observed new @xmath0 secondary standards from the ukirt ( @xmath16 ) faint standards list ( hawarden et al . , 2001 ) , selecting stars that were expected to have @xmath17 . typically in a full night around 30 stars were observed , divided equally between the three groups : bright @xmath0 primary standards , faint @xmath0 secondary standards and bright @xmath1 primary standards . the ircam field of view is 20@xmath115 . observations consisted of sets of four or eight images with the telescope pointing slightly offset between each ; the offsets were kept small enough that the pattern of pointings would fit inside the 20@xmath18 field . consecutive pairs of images were subtracted and the set of two or four subtracted pairs were combined to give an image containing one positive and one negative detection of the source . total exposure time for the bright @xmath0 standards was 80 seconds and for the fainter stars it was typically 480 seconds , in both cases made up of sets of four or eight 20-second exposures each in turn consisting of 100 coadded 0.2-second integrations . exposure time at @xmath1 was usually 216 seconds , made up of sets of four or eight 9-second exposures consisting of 75 coadded 0.12-second integrations . overheads are about a factor of two due to the extremely short integrations . a flatfield was created by median filtering the set of four or eight normalised and cleaned observations . the cleaning removed blemishes on scales smaller than 1 arcsec , achieved by smoothing with a box filter and iteratively rejecting pixels more than two standard deviations from the neighbourhood mean . it was not necessary to mask objects when creating the flatfield because of the extremely high sky counts in every image . the flatfielded subtracted images were registered using the telescope offsets accurate to better than 0.5 arcsec converted to integer numbers of pixels to avoid resampling . mosaics of the shifted images were formed using the mean at each pixel , thus preserving flux . counts on and off target were dominated in all cases by the high sky background and as the stars were reduced in a relative sense ( described below ) , applying a correction for non linearity was not necessary . photometry was carried out on both the positive and negative images of the source in the individual sky - subtracted and flatfielded frames as well as in the final flatfielded mosaic . the photometry aperture was automatically positioned by the software at the source centroid ; the source aperture size used was 5@xmath110 . although the background counts were close to zero , since consecutive frames had been subtracted from one another , a concentric `` sky '' aperture was used with inner and outer radii at 6@xmath115 and 10@xmath110 . the sky value was an iteratively clipped mean , emulating the mode . errors were estimated in the usual way using the variance of the pixel - to - pixel signals in the star and background apertures . the resulting error estimates were consistent with the difference in the photometry between the positive and negative image of the source , and with the scatter of the results about the observed extinction curves ( see below ) . as a further check , for a single night s observations , data variances were created using the read noise and poisson statistics , and propagated through the processing steps . the photometric errors calculated using the data variance , yielded values some 20 percent larger for the mosaics than the error estimates used in this paper . typically two to four stars were observed repeatedly ( 4 to 7 times ) during the night to determine the atmospheric extinction ; these stars were brighter stars chosen for their location in the sky . these extinction stars were observed at airmasses as high as 2.0 , typically other stars were observed at an airmass less than 1.6 . the extinction was determined by a linear fit to the observed instrumental magnitude as a function of airmass . the results ranged from 0.08 to 0.15 magnitudes / airmass ( hereinafter mag / am ) at @xmath0 , with an average value of 0.11 mag / am , and ranged from 0.18 to 0.29 mag / am at @xmath1 , with an average value of 0.23 mag / am . the error on the extinction value was on average 0.03 mag / am at @xmath0 and 0.05 mag / am at @xmath0 . tokunaga et al . ( 2002 ) calculate the extinction for the mko nir @xmath0 and @xmath1 filters ; they find that a linear fit should be accurate to better than 0@xmath2005 . the slope should not be strongly dependent on the amount of water in the atmosphere : for a range in precipitable water vapour of 0.5 mm to 4.0 mm the @xmath0 extinction should vary from 0.09 to 0.11 mag / am and the @xmath1 extinction from 0.20 to 0.24 mag / am . our observed range of extinction values appears to be larger than predicted . however , the measurement errors are such that this this difference is not significant , and we note that the means of our measured values agree with the predictions of tokunaga et al . no significant correlation between our measured extinctions and the atmospheric water vapour content is evident . the stars not used for extinction were observed once or twice a night . each night s data was reduced in a relative sense : after using the extinction stars to define a mean extinction value , the primary targets were used to define a mean zeropoint at an airmass of unity . the fainter secondary standards were calibrated using these values for zeropoint and extinction . as each night s data were reduced , the deviation from the ensemble mean zeropoint for that night of the individual zeropoints from each primary standard was derived . this was applied as a correction to the catalogue magnitudes for these stars , producing an evolving working catalogue to replace the original . the evolving value was used in deriving the ensemble zeropoint , and individual deviations , on the next night , and the process repeated . gives our @xmath0 results for the stars from the ukirt bright standards list . spectral types for these stars were found from the simbad database . the number of measurements is the number of nights on which the star was observed , i.e. if the star was observed more than once on a given night the mean result is counted as a single independent observation . results were weighted according to the measurement error for each night . gives the @xmath0 results for the fainter stars from the ukirt faint standards of hawarden et al . ( 2001 ) , whence the spectral types are taken . gives the @xmath1 results , where , again , the number of measurements are the number of nights observed and spectral types are from simbad . for all of tables 2 through 4 , the value of @xmath19 given in the sixth column is the value of the standard error of the mean over all the nights included in the measurements ; accordingly , no @xmath19 value is shown for stars measured on only one night . this @xmath19 may underestimate the true external error , as we discuss below . for the stars observed more than three times , any measurement that deviated from the mean by more than three sigma was rejected typically these deviations were @xmath200@xmath208 . @xmath0 measurements were rejected for hd18881 , sao112626 , hd84800 , hd161903 , fs104 , fs123 , fs125 , fs147 , fs149 and fs155 . @xmath1 measurements were rejected for hd84800 and hd129653 . in all cases single measurements were discarded , except for sao112626 and fs155 where two @xmath0 measurements were discarded . we interpret these deviant values as simply bad data and not as evidence of variability at @xmath0 or @xmath1 . all the stars have been measured on several nights at near infrared and , in most cases , optical wavelengths . the bright ( primary ) stars were observed in the @xmath7 , @xmath8 , @xmath9 and @xmath3 bands on numerous occasions at ukirt ( see above ) and at ctio and kpno ( elias et al . , 1982 ) over more than a decade . the faint stars have been observed at @xmath16 an average of 7 ( minimum : 3 , maximum : 12 ) times over the period 19941998 ( hawarden et al . 2001 ) and in two cases are landolt ( 1992 ) standards with numerous observations in the optical . none have been suspected to vary . since stellar variability is usually larger in amplitude at shorter wavelengths ( barring large changes in atmospheric structure , such as dust formation , unlikely in stars as carefully selected for stability and normality as these ) changes of significant amplitude must be regarded as unlikely . an exception to this may be fs 101 , for which the error in the mean @xmath0 value remained high despite repeat measurements . this f0 star did not show any signs of variability at @xmath16 ( hawarden et al . 2001 ) but seven @xmath0 measurements showed a range of 0@xmath21 with a standard error in the mean of 0@xmath205 . we note that the sample includes two b supergiants , bs 696 and bs 8541 , as @xmath1 standards . although it is possible that free free emission from potentially variable stellar winds contributes to their @xmath1 flux there is currently no evidence of variability . sinton & tittemore ( 1984 ) observed these stars 67 times and they have also been observed numerous times at ukirt ( bs 8541 is flagged as a frequently observed star in the ukirt bright standards list ) . note that if there is a significant contribution from a stellar wind then the stars will have atypical colours and should not be used for system transformations . combines all the measurements in one table , and also lists right ascension and declination , proper motion and spectral type . here we have estimated the external errors as follows . on individual nights the scatter around the mean extinction curve for stars observed more than once was typically 0@xmath202 for the bright @xmath0 standards , and 0@xmath203 for the fainter @xmath0 standards and for the @xmath1 standards . this is only slightly worse than the average calculated error of an individual measurement , based on signal to noise statistics . accordingly , if the star was observed on @xmath21 nights then our adopted uncertainty in is the larger of @xmath22/ \sqrt(n-1)$ ] or the internal standard deviation of the mean given in tables 13 . the number of observations in is the number of nights on which the star was observed in each filter . a combination of lack of photometric weather and the replacement of ircam by another instrument necessitated the termination of this programme when some stars had fewer than three observations . these stars , and those with estimated error larger than 0@xmath203 , should be treated with appropriate caution , as perhaps should the two b supergiants mentioned above . figure 2 plots , for the brighter stars , the difference between our @xmath0 and @xmath1 magnitudes on the mko system and the previously listed values on the ukirt @xmath0 and broadband @xmath4 systems . the differences are plotted as a function of colour , expressed as @xmath23 on the ukirt system ( not mko ) , and of brightness at @xmath0 or @xmath1 . at @xmath0 the mean absolute difference between the current and previous measurements is 0@xmath202 , consistent with our uncertainties and the estimated error in the older measurements ( e.g. the two stars with @xmath24 in sinton & tittemore ( 1984 ) have a quoted uncertainty of 0@xmath202 and 0@xmath205 in their ) . there is no evidence of a colour term ; instead the stars with the largest deviations from the previously tabulated value are fainter , suggesting larger errors in the original measurements . the latest spectral type in this sample is m5.5 . it is known that for ultracool objects , of spectral type l5 and later , there will be a difference in magnitude measured with the previous ukirt @xmath0 and the current mko nir @xmath0 filter . this is due to the onset of methane absorption at the blue edge of the mko nir bandpass ( leggett et al . , 2002 ) . such objects are not currently used as standards . at @xmath1 the mean absolute difference between the current and previous measurements is 0@xmath205 , again consistent with our estimated errors and those of the older measurements ( e.g. the two stars with @xmath25 in sinton & tittemore ( 1984 ) have quoted errors of 0@xmath203 and 0@xmath206 ) . again , the deviation is larger for fainter targets suggesting a larger error in the original measurement . there are insufficient red stars in common to determine whether or not a colour term exists between @xmath4 and @xmath1 magnitudes . although a dependency was expected for types k and later due to photospheric co absorption , we have synthesised broadband @xmath4 and @xmath1 magnitudes for a late m dwarf and for an early k giant ( using models from hauschildt , allard & baron ( 1999 ) for the former and the observationally based templates of cohen et al . ( 1999 ) for the latter ) and found the difference to be only 0@xmath2005 , presumably because both filters include the co band . in any case , as broadband @xmath4 is no longer used this is not an issue for modern work . we have presented new @xmath0 observations , using the mko nir filter , of 25 stars with @xmath26 . the average internal standard error of the mean result for each star is 0@xmath2010 , the estimated external error ranges from 0@xmath2010 to 0@xmath2025 . most of these stars have previously tabulated @xmath0 values on the `` ukirt '' system . the difference between the ukirt and mko values are typically 0@xmath202 , with one larger deviation of 0@xmath209 for the faintest star in the sample . there is no evidence of a colour dependency in @xmath27 for stars as late as m5.5 . data with the same filter are presented for 21 stars with @xmath28 , taken from the ukirt @xmath16 faint standards list . the average internal standard error of the mean results is 0@xmath202 , the estimated external error ranges from 0@xmath202 to 0@xmath205 . these stars will be useful as standards for larger telescopes , and convenient for programs on such telescopes which require calibration of all four of the @xmath29 bands . we also present @xmath1 observations , using the mko nir filter , of 31 stars with @xmath30 . the average internal standard error of the mean results is 0@xmath202 , while the estimated external error ranges from 0@xmath202 to 0@xmath205 . most of these stars have previously tabulated broadband @xmath4 magnitudes ; and the difference between @xmath4 and mko nir @xmath1 is typically 0@xmath205 although there are two stars that differ by @xmath310@xmath21 ; these are fainter stars that most likely have larger uncertainties in the original measurements . the new data will allow more accurate calibration of @xmath4band photometry on a wide range of telescopes . systematic errors in the photometry due to non linear extinction or variable water vapour are calculated to be @xmath124 millimags at @xmath0 and @xmath128 millimags at @xmath1 , for sites as low as 2 km . investigation of the transmissive or reflective elements of ukirt and its imagers implies that commonly used optical elements will introduce variations in the photometric system of @xmath123 millimag . hence the results presented here are generally applicable to other observatories . ukirt , the united kingdom infrared telescope , is operated by the joint astronomy centre on behalf of the u.k . particle physics and astronomy research council ( pparc ) . this work would not have been possible without the dedicated effort of all the ukirt staff , past and present ; in particular we note the important contribution of the late sidney arakaki , without which none of the early ukirt photometry would have been possible . we are very grateful to mark casali , tim chuter , maren hauschildt purves , kevin krisciunas , andy longmore , erik starman , mike wagner and peredur williams , as well as vacation student stuart k. koyonagi . we thank visiting observers dave golimowski and gene magnier for allowing us to incorporate their calibration observations in these results . we also thank the referee for a careful reading of the manuscript and for suggestions that lead to substantial improvements . orac dr was used to reduce the observations for this paper . dr was developed at the joint astronomy centre ; the concept and early recipes originated at the astronomy technology centre , edinburgh . the application engines used in orac dr were supplied and excellently supported by the starlink project , which is run by the uk central laboratory for the research councils on behalf of pparc . we thank all the programmers involved .
we present @xmath0 and @xmath1 photometry , obtained at ukirt using the mauna kea observatories near ir ( mko nir ) filter set , for 46 and 31 standard stars , respectively . the @xmath0 standards include 25 from the ukirt in house `` bright standards '' with magnitudes deriving from elias et al . ( 1982 ) and observations at the irtf in the early 1980s , and 21 fainter stars . the @xmath1 magnitudes derive from the results of sinton & tittemore ( 1984 ) . we estimate the average external error to be 0@xmath2015 for the bright @xmath0 standards and 0@xmath2025 for the fainter @xmath0 standards , and 0@xmath2026 for the @xmath1 standards . the new results provide a network of homogeneously observed standards , and establish reference stars for the mko system , in these bands . they also extend the available standards to magnitudes which should be faint enough to be accessible for observations with modern detectors on large and very large telescopes .
Google Earth / Reuters Hawthorne Army Depot in western Nevada is seen in this Aug. 30, 2010 satellite image courtesy of Google Earth. Six U.S. Marines were killed and eight wounded when a mortar exploded during a live-fire training exercise late Monday at an Army munitions depot in the Nevada desert, military officials told NBC News. A 60-millimeter mortar exploded in a tube at Hawthorne Army Depot as Marines were preparing to fire it, the officials said. NBC affiliate KRNV in Reno reported that an explosion rocked the facility, just east of the California line, just before 10 p.m. The injured were taken to two hospitals. Stacy Kendall, a spokeswoman for Renown Regional Medical Center, said that it was treating eight people wounded in the blast, three in serious condition and five in fair condition. She said that the injuries included traumas and fractures. The depot is a 147,000-acre storage facility for ammunition and other equipment being taken out of service and a training facility for Special Operations forces preparing to deploy to the Middle East. This story was originally published on ||||| LAS VEGAS A mortar explosion at a U.S. Army munitions depot in Nevada killed seven Marines from Camp Lejeune, North Carolina, and injured seven other service members during a live-fire training exercise, military officials said on Tuesday. A Marine Corps official said a 60mm mortar round exploded prematurely Monday night during training at the Hawthorne Army Depot in western Nevada. The cause was under investigation. "The Marines were conducting live fire and maneuver training at the Hawthorne Army depot," Brigadier General Jim Lukeman told a news conference in North Carolina. "A mortar round exploded in the mortar tube, causing the deaths of seven and injuring seven others. We don't know yet what caused this malfunction." The blast was among the deadliest such training accidents on U.S. soil in recent years. Last February, seven Marines were killed when two helicopters collided during an exercise along the California-Arizona border. The Marines killed on Monday had been undergoing training for the past month at the Marine Corps Mountain Warfare Training Center in Bridgeport, California and at Hawthorne. "This is part of the type of training that we do just to maintain a force in readiness," Lukeman said. "It's not specifically linked to a nearby deployment." The U.S. Marines ordered a blanket suspension of the use of 60mm mortars pending a review after the blast, Marine Corps spokeswoman Captain Kendra Motz said in a statement. The explosion's victims were airlifted to Renown Regional Medical Center in Reno with injuries that included penetration trauma, fractures and vascular injuries, said Stacy Kendall, a spokeswoman for the medical center. Six Marines and a Navy sailor were wounded. Of those, six were in serious or very serious condition, while a seventh suffered minor injuries, Lukeman said. NIGHTTIME ACCIDENT The explosion occurred at close to 10 p.m. PDT (5 a.m. GMT Tuesday) during an exercise at the Hawthorne depot, about 92 miles southeast of Reno, said facility manager Russ Collier. The identities of the dead and injured have not been made public, but will be released after their families are notified. Defense Secretary Chuck Hagel was receiving updates on the accident, Pentagon spokesman George Little said, adding that the incident struck a nerve with Hagel, himself an infantry veteran of the Vietnam war. "This brought back memories of a training accident when he was in the U.S. Army when two soldiers were killed in a training accident, so he takes these incidents very much to heart," Little said. Nevada Governor Brian Sandoval and Senate Majority Leader Harry Reid of Nevada also expressed condolences. Hawthorne Army Depot is a 147,000-acre site used for the storage and destruction of demilitarized ammunition. Its location in Nevada's isolated high desert is also considered an ideal training environment for Special Operations forces preparing for deployments to Southwest Asia, according to a U.S. military website. The facility was established as a naval staging area for bombs, rockets and ammunition, and was used by the Navy during most of World War Two. It was transferred to the Army in 1977. The accident came a week after a U.S. military plane assigned to a Washington state Naval Air Station crashed during a routine training flight, killing all three crew members on board. (Reporting by Chris Francescani in New York, David Alexander in Washington D.C. and Cynthia Johnston in Las Vegas; Writing by Chris Francescani and Steve Gorman; Editing by Paul Thomasch, Nick Zieminski, Leslie Gevirtz)
– Seven US Marines are dead after an explosion at Hawthorne Army Depot in Nevada last night, military officials tell NBC News. The accident occurred at an ammunition storage facility during a live-fire training exercise, when a 60-millimeter mortar exploded in a tube as Marines were getting ready to fire it. Another eight Marines were wounded; three are in serious condition. The 147,000-acre depot is used for storing and destroying demilitarized ammo, Reuters reports.
computational fluid dynamics ( cfd ) simulations have been widely used in aerospace , mechanical , and chemical industries to support engineering design , analysis , and optimization . two decades ago when large eddy simulations ( les ) started gaining popularity with the increasing availability of computational resources , it was widely expected that les would gradually displace and eventually replace reynolds - averaged navier - stokes ( rans ) equations in industrial computational fluid dynamics ( cfd ) work - flows for decades to come . in the past two decades , however , while les - based methods ( including resolved les , wall - modeled les , and hybrid les / rans methods ) did gain widespread applications , and the earlier hope certainly did not diminish , the predicted time when these methods would replace rans has been significantly delayed . this observation is particularly relevant in light of the recent discussions on the ending of the `` moore s law era '' with transistor sizes approaching their theoretical lower limit @xcite . rans solvers , particularly those based on standard eddy viscosity models ( e.g. , @xmath0@xmath1 @xcite , @xmath0@xmath2 @xcite , s a @xcite , and k@xmath2sst @xcite , are still and will remain the dominant tool for industrial cfd in the near future . this is likely to be true even in mission critical applications such as aircraft design . interestingly , even the advanced rans models such as reynolds stress transport models @xcite and explicit algebraic reynolds stress models @xcite have not seen much development in the past few decades . these advanced models are computationally more expensive and less robust compared to the standard eddy viscosity rans models . as such , it is still practically important to further develop the standard rans models for industrial cfd applications . however , improving the predictive capabilities of these models is critical yet technically challenging . while traditional development of turbulence models has focused on incorporating more physics to improve predictive capabilities , an alternative approach is to utilize data . in the past few years , a number of data - driven approaches have been proposed . researchers have investigated the use of both offline data ( i.e. , existing dns data for flows different from that to be predicted @xcite ) and online data ( streamed monitoring data from the flow to be predicted @xcite ) . dow and wang @xcite used direct numerical simulation ( dns ) data from a plane channel flow to infer the full - field discrepancy in the turbulent viscosity @xmath3 modeled by the @xmath0@xmath2 model . to predict flows in channels with wavy boundaries , they modeled the ( log-)discrepancies of @xmath3 in the new flows as gaussian random fields , with the discrepancy field inferred above as mean . duraisamy and co - workers @xcite introduced a full - field multiplicative discrepancy term @xmath4 into the production term of the transport equations of turbulent quantities ( e.g. , @xmath5 in the sa model and @xmath2 in the @xmath0@xmath2 models ) . they used dns data to calibrate and infer uncertainties in the @xmath4 term . it is expected that the inferred discrepancy field can provide valuable insights to the development of turbulence model and can be used to improve rans predictions in similar flows . xiao et al . @xcite used sparse velocity measurements ( online data ) to infer the full - field discrepancies @xmath6 in the rans - predicted reynolds stress tensors , or more precisely the physical projections thereof ( turbulent kinetic energy , anisotropy , and orientations ) . throughout this paper it is understood that @xmath7 indicates the physical projections and not the individual components of the reynolds stress tensor . good performance was demonstrated on several canonical flows including flow past periodic hills , flow in a square duct @xcite , and flow past a wing body junction @xcite . all three approaches @xcite discussed above can be considered starting points toward the same destination : the capability of predictive turbulence modeling by using standard rans models in conjunction with offline data . to this end , the respective discrepancies terms ( @xmath8 , @xmath4 , and @xmath6 ) are expected to be extrapolated to similar yet different flows . these contributions are all relatively recent and much of the research is still on - going . duraisamy et al . @xcite performed _ a priori _ studies to show the potential universality of their discrepancy term @xmath4 among a class of similar flows , but their performances in _ a posteriori _ tests , i.e. , using the calibrated discrepancy in one flow to predict another flow , have yet to be demonstrated . dow and wang @xcite extrapolated the logarithmic discrepancies @xmath8 calibrated in the plane channel flow to flows in channel with slightly wavy walls , where velocity predictions were made . similarly , further pursuing the approach of xiao et al . @xcite , wu et al . @xcite showed that the reynolds stress discrepancy calibrated with sparse velocity data can be extrapolated to flows at reynolds number more than an order of magnitude higher than that in the calibration case . the extrapolated discrepancy has lead to markedly improved predictions of velocities and other quantities of interest ( qois ) , showing the potential of the approach in enabling data - driven predictive turbulence modeling . however , an intrinsic limitation in the approach of wu et al . @xcite is that they inferred the functions @xmath9 , or simply denoted as @xmath10 , in the space of _ physical coordinates _ therefore , strictly speaking they only demonstrated that the discrepancy @xmath6 can be extrapolated to flows in the same geometry at the same location . consequently , their attempts of extrapolation to the flow in a different geometry ( e.g. , from a square duct to a rectangular duct ) encountered less success . the approach of dow and wang @xcite would share the same limitation since they built gaussian random fields indexed by the physical coordinates @xmath11 . a natural extension that overcomes the key limitation in the calibration prediction approach of wu et al . @xcite is to build such functions in a space of well - chosen features @xmath12 instead of physical coordinates @xmath11 . despite its limitations , a key factor in the success of the original approach is that the reynolds stress discrepancies are formulated on its projections such as the anisotropy parameters ( @xmath13 and @xmath14 ) and orientation ( @xmath15 ) of the reynolds stresses and not directly on the individual components . these projections are normalized quantities @xcite . we shall retain this merits in the current approach and thus use data to construct functions @xmath16 instead of @xmath17 . this extension would allow the calibrated discrepancies to be extrapolated to a much wide range of flows . in other words , the discrepancies of the rans - predicted reynolds stresses can be quantitatively explained by the mean flow physics . hence , these discrepancies are likely to be universal quantities that can be extrapolated from one flow to another , at least among different flows sharing the same characteristics ( e.g. , separation ) . as such , discrepancies in reynolds stress projections are suitable targets to build functions for . with the function targets identified , two challenges remain : ( 1 ) to identify a set of mean flow features based on which the discrepancies functions @xmath16 can be constructed and ( 2 ) to choose a suitable method for constructing such functions . duraisamy and co - workers @xcite identified several features and used neural network to construct functions for the multiplicative discrepancy term . ling and templeton @xcite provided a richer and much more complete set of features in their pioneering work , and they evaluated several machine learning algorithms to predict point - based binary confidence indicators of rans models @xcite . ling et al . @xcite further used machine learning techniques to predict the reynolds stress anisotropy in jet - in - cross flows . based on the success demonstrated by ling and co - workers @xcite , we will use machine learning to construct the functions @xmath16 in the current work . specifically , we will examine a class of supervised machine learning techniques , where the objective of the learning is to build a statistical model from data and to make predictions on a response based on one or more inputs @xcite . this is in contrast to unsupervised learning , where no response is used in the training or prediction , and the objective is to understand the relationship and structure of the input data . unsupervised learning will be explored as an alternative approach in future works . the objective of this contribution is to present an approach to predict reynolds stress modeling discrepancies in new flows by utilizing data from flows with similar characteristics as the prediction flow . this is achieved by training regression functions of reynolds stress discrepancies with the dns database from the training flows . in light of the consensus in the turbulence modeling community that the reynolds stresses are the main source of model - form uncertainty in rans simulations @xcite , the current work aims to improve the rans modeled reynolds stresses . in multi - physics applications the qois might well be the reynolds stresses and/or quantities that directly depend thereon . in these applications the current work is significant by itself in that it would enable the use of standard rans models in conjunction with an offline database to provide accurate reynolds stress predictions . moreover , the improvement of reynolds stresses enabled by the proposed method is an important step towards a data - driven turbulence modeling framework . however , the reynolds stresses corrected by the constructed discrepancy function from dns databases can not necessarily guarantee to obtain improved mean flow fields . there are a number of challenges associated with propagating the improvement of reynold stresses through rans equation to the mean velocity field , which will be addressed in future works . the rest of this paper is organized as follows . section 2 introduces the components of the predictive framework , including the choice of regression inputs and responses as well as the machine learning technique used to build the regression function . section 3 shows the numerical results to demonstrate the merits of the proposed method . further interpretation of the feature importance and its implications to turbulence model development are discussed in section 4 . finally , section 5 concludes the paper . the overarching goal of the current and companion works is a physics - informed machine learning ( piml ) framework for predictive turbulence modeling . here , `` physics - informed '' is to emphasize the attempt of accounting for the physical domain knowledge in every stage of machine learning . the problem targeted by the piml framework can be formulated as follows : given high - fidelity data ( e.g. , reynolds stresses from dns or resolved les ) from a set @xmath18 of @xmath19 training flows , the framework shall allow for using standard rans turbulence models to predict a new flow @xmath20 for which data are not available . the flows @xmath21 for which high - fidelity simulation data are available are referred to as _ training flows _ , and the flow @xmath20 to be predicted is referred to as _ test flow_. the lack of data in test flows is typical in industrial cfd simulations performed to support design and optimization . furthermore , we assume that the training flows and the test flow have similar complexities and are dominated by the same characteristics such as separation or shock boundary layer interaction . this scenario is common in the engineering design process , where the test flow is closely related to the training flows . ultimately , the envisioned machine learning framework will be used in scenarios where the training flows consist of a wide range of elementary and complex flows with various characteristics and the test flow has a subset or all of them . however , the latter scenario is much more challenging and is outside the scope of the current study . considering the proposed method is a completely new paradigm , we decide to take small steps by starting from the closely related flows and to achieve the overarching goal gradually . in the proposed approach we utilize training data to construct functions of the discrepancies ( compared to the dns data ) in the rans - predicted reynolds stresses and use these functions to predict reynolds stresses in new flows . the procedure is summarized as follows : 1 . perform baseline rans simulations on both the training flows and the test flow . 2 . compute the feature vector field @xmath22 , e.g. , pressure gradient and streamline curvature , based on the rans - predicted mean flow fields for all flows . 3 . compute the discrepancies field @xmath23 in the rans modeled reynolds stresses for the training flows based on the high - fidelity data . 4 . construct regression functions @xmath24 for the discrepancies based on the training data prepared in step 3 . compute the reynolds stress discrepancies for the test flow by querying the regression functions . the reynolds stresses can subsequently be obtained by correcting the baseline rans predictions with the evaluated discrepancies . in machine learning terminology the discrepancies @xmath6 here are referred to as _ responses _ or _ targets _ , the feature vector @xmath12 as _ input _ , and the mappings @xmath25 as _ regression functions_. a regression function @xmath26 maps the input feature vector @xmath12 to the response @xmath27 , and the term `` function '' shall be interpreted in a broad sense here . that is , depending on the regression technique used , it can be either deterministic ( e.g. , for linear regression ) or random ( e.g. , gaussian process ) @xcite , and it may not even have an explicit form . in the case of random forests regression used in this work @xcite , the mapping does not have an explicit expression but is determined based on a number of decision trees . in the procedure described above , after the baseline rans simulations in step 1 , the input feature fields are computed in step 2 , the training data are prepared in step 3 , and the regression functions are constructed in step 4 . finally , the regression functions are evaluated to make predictions in step 5 . it is worth noting that in each stage domain knowledge is incorporated , e.g. , physical reasoning for identification of input features and consideration of realizability constraints of reynolds stress in learning - prediction process . each component is discussed in detail below . the choice of features and responses are presented in sections [ sec : feature ] and [ sec : discrepancy ] , respectively , and the machine learning algorithm chosen to build the regression function is introduced in section [ sec : regression ] . as has been pointed out in section [ sec : intro ] , mean flow features are better suited as input of the regression function than physical coordinates as they allow the constructed functions to predict flows in different geometries . ling and templeton @xcite proposed a rich set of twelve features based on clear physical reasoning . the set of features used in the present study mostly follow their work , except that we excluded the feature `` vortex stretching '' ( input 8 in table ii of ref . @xcite ) . this feature is present only in three - dimensional flows , but the test cases presented here are two - dimensional flow . we excluded two additional features related to linear and nonlinear eddy viscosities ( features 6 and 12 in ref . these quantities were specifically chosen for evaluating qualitative confidence indicators of rans predictions and , in our opinion , are not suitable input for regression functions of reynolds discrepancies . finally , experiences in the turbulence modeling communities suggest that mean streamline curvature has important influences on the predictive performance of rans models @xcite . therefore , curvature is included as an additional feature . the complete list of the mean flow features chosen as regression inputs in this work is summarized in table [ tab : feature ] . in choosing the mean flow features as regression inputs , we have observed a few principles in general . first , the input and thus the obtained regression functions should be galilean - invariant . quantities that satisfy this requirement include all scalars and the invariants ( e.g. , norms ) of vectors and tensors . an interesting example is the pressure gradient along streamline ( see feature @xmath28 in table [ tab : feature ] ) . while neither velocity @xmath29 nor pressure gradient @xmath30 ( both being vectors ) is galilean - invariant by itself and thus is not a suitable input , their inner product @xmath31 is second , since the truth of the mean flow fields in the test flows are not available , an input should solely utilize information of the mean flow field produced by the rans simulations @xcite . therefore , all of the adopted features are based on rans - predicted pressure @xmath32 , velocity @xmath33 , turbulent kinetic energy @xmath0 , and distance @xmath34 to the nearest wall . finally , to facilitate implementation and avoid ambiguity , only local quantities ( i.e. , cell- or point - based quantities in cfd solvers ) of the flow field are used in the formulation of features , with the distance @xmath34 to nearest wall being a notable exception . this principle is similar to that in choosing variables for developing turbulence models @xcite . the interpretation of most feature variables are evident from the brief descriptions given in the table , but a few need further discussions . first , feature @xmath35 ( q - criterion ) is based on the positive second invariant @xmath36 of the mean velocity gradient @xmath37 , which represents excess rotation rate relative to strain rate @xcite . for incompressible flows , it can be computed as @xmath38 , where @xmath39 and @xmath40 are rotation rate and strain rate tensors , respectively ; @xmath41 and @xmath42 , with superscript @xmath43 indicating tensor transpose and tr indicating trace . the q - criterion is widely used in cfd simulations as a post - processing tool to identify vortex structures for the visualization of flow structures @xcite . second , the wall distance based reynolds number @xmath44 in @xmath45 is an indicator to distinguish boundary layers from shear flows . this is an important feature because rans models behave very differently in the two types of flows . this quantity is frequently used in wall functions for turbulence models . third , feature @xmath46 defines the deviation from orthogonality between the velocity and its gradient @xcite , which indicates the deviation of the flow from parallel shear flows ( e.g. , plane channel flows ) . since most rans models are calibrated to yield good performance on parallel shear flows , this deviation is usually correlated well with large discrepancies in rans predictions . however , since it only accounts for misalignment angle and not the velocity magnitude , in regions with near - zero velocities this quantity becomes the angle formed by two zero - length vectors and is thus mostly noise . finally , we remark that most of the features in table [ tab : feature ] including the q - criterion and wall - distance based reynolds number are familiar to cfd practitioners . most of the features presented in table [ tab : feature ] are formulated as ratios of two quantities of the same dimension , either explicitly ( @xmath35 , @xmath47 , @xmath48 , @xmath49 , @xmath50 ) or implicitly ( @xmath51 and @xmath45 ) . hence , they are non - dimensional by construction . features @xmath28 and @xmath46 involve inner product of vectors or tensors , and thus they are normalized by the magnitude of the constituent vectors or tensors . finally , feature @xmath52 ( streamline curvature ) is normalized by @xmath53 , where @xmath54 is the characteristics length scale of the mean flow , chosen to be the hill height @xmath55 ( see fig . [ fig : flowgeo ] ) in the numerical examples . we followed the procedure of ling and templeton @xcite to normalize the features . except for feature @xmath45 , each element @xmath56 in the input vector @xmath12 is normalized as : @xmath57 where the summation on repeated indices is not implied , @xmath58 are raw values of the features , and @xmath59 are the corresponding normalization factors . this normalization scheme limits the numerical range of the inputs within @xmath60 $ ] and thus facilitates the regression . the normalization is not needed for feature @xmath45 ( wall distance based reynolds number ) since it is already in a non - dimensional form and in a limited range @xmath61 $ ] . it can be seen that the choices of features and normalization factors heavily rely on physical understanding of the problem ( turbulence modeling ) . that is , in the present data - driven modeling framework , the data are utilized only _ after _ physical reasoning from the modeler has been applied . this task can be a burden in certain applications . it is worth noting that the recent work of ling et al . @xcite aimed to relieve the modeler from such burdens by using a basis of invariants of tensors relevant in the specific application ( e.g. , strain rate @xmath40 in turbulence modeling ) . their work has the potential to systematically construct the input features based on raw physical variables and thus makes data - driven modeling even `` smarter '' . p2.0 cm | p5.0 cm p3.0 cm p4.0 cm feature ( @xmath56 ) & description & raw feature ( @xmath58 ) & normalization factor ( @xmath62 ) + @xmath35 & ratio of excess rotation rate to strain rate ( q - criterion ) & @xmath63 & @xmath64 + @xmath51 & turbulence intensity & @xmath0 & @xmath65 + @xmath45 & wall - distance based reynolds number & @xmath66 & not applicable@xmath67 + @xmath28 & pressure gradient along streamline & @xmath68 & @xmath69 + @xmath47 & ratio of turbulent time scale to mean strain time scale & @xmath70 & @xmath71 + @xmath48 & ratio of pressure normal stresses to shear stresses & @xmath72 & @xmath73 + @xmath46 & non - orthogonality between velocity and its gradient @xcite & @xmath74 & @xmath75 + @xmath49 & ratio of convection to production of tke & @xmath76 & @xmath77 + @xmath50 & ratio of total to normal reynolds stresses & @xmath78 & @xmath0 + @xmath52 & streamline curvature & @xmath79 where @xmath80 , @xmath81 & @xmath82 + in section [ sec : motivation ] the reynolds stress discrepancies @xmath83 have been identified as the responses for the regression functions . the response quantities should also be based on galilean invariant quantities due to the same consideration as in the feature choice . as such , individual components of the reynolds stresses or the discrepancies based thereon are not suitable , but those based on their eigenvalues or invariants are preferred . in turbulence modeling , the lumley triangle has been widely used for the analysis of turbulence states related to realizability @xcite . it is formulated based on the second and third invariants ( @xmath84 and @xmath85 ) of the anisotropy tensor . recently , banerjee et al . @xcite proposed an improved formulation in which the eigenvalues of the anisotropy tensor are mapped to barycentric coordinates as opposed to the variants @xmath84 and @xmath85 as in the lumley triangle . an important advantage of their formulation is that the mapping to barycentric coordinates is linear , which is in contrast to the nonlinear mapping to invariants @xmath84 and @xmath85 . therefore , barycentric coordinate provides a non - distorted visual representation of anisotropy and is easier to impose realizability constraints . the formulation of discrepancy starts with the eigen - decomposition of the reynolds stress anisotropy tensor @xmath86 : @xmath87 where @xmath0 is the turbulent kinetic energy , which indicates the magnitude of @xmath88 ; @xmath89 is the second order identity tensor ; @xmath90 $ ] and @xmath91 $ ] with @xmath92 are the orthonormal eigenvectors and eigenvalues of @xmath86 , respectively , indicating its shape and orientation . in the barycentric triangle , the eigenvalues @xmath93 , @xmath94 , and @xmath95 are mapped to the barycentric coordinates @xmath96 as follows : [ eq : lambda2c ] @xmath97 with @xmath98 . as shown in fig . [ fig : bary ] , the barycentric coordinates of a point indicate the portion of areas of three sub - triangles formed by the point and with edges of barycentric triangle . for example , a point located on the top vertex corresponds to @xmath99 while a point located on the bottom edge has @xmath100 = 0 . similar to the lumley triangle , all realizable turbulences are enclosed in the barycentric triangle ( or on its edges ) and have positive barycentric coordinates @xmath101 , @xmath102 , and @xmath100 . the barycentric triangle has been used by emory et al . @xcite as a mechanism to impose realizability of reynolds stresses in estimating uncertainties in rans simulations . placing the triangle in a cartesian coordinate system @xmath103 , the location of any point within the triangle is a convex combination of those of the three vertices , i.e. , @xmath104 where @xmath105 , @xmath106 , and @xmath107 denote coordinates of the three vertices of the triangle . an advantage of representing the anisotropy of reynolds stress in the barycentric coordinates is that it has a clear physical interpretation , i.e. , the dimensionality of the turbulence state @xcite . typically , the standard - rans - predicted reynolds stress at a near wall location is located close to the isotropic , three - component state ( vertex 3c - i ) in the barycentric triangle , while the truth is near the two - component limiting states ( bottom edge ) . moreover , the spatial variations from the near - wall region to the shear flow region are indicated as arrows in fig . [ fig : bary ] . it is clear that the trend of spatial variation predicted by a standard rans model is opposite to that of the truth . the three mutually orthogonal , unit - length eigenvectors @xmath108 , @xmath109 , and @xmath110 indicate the orientation of the anisotropy tensor . they can be considered a rigid body and thus its orientation has three degrees of freedom , although they have nine elements in total . we use the euler angle with the @xmath111@xmath112@xmath113 convention to parameterize the orientation following the convention in rigid body dynamics @xcite . that is , if a local coordinate system @xmath114@xmath115@xmath111 spanned by the three eigenvectors of @xmath116 was initially aligned with the global coordinate system ( @xmath117@xmath118@xmath119 ) , the current configuration could be obtained by the following three consecutive intrinsic rotations about the axes of the local coordinate system : ( 1 ) a rotation about the @xmath111 axis by angle @xmath120 , ( 2 ) a rotation about the @xmath114 axis by @xmath121 , and ( 3 ) another rotation about its @xmath111 axis by @xmath122 . the local coordinate axes usually change orientations after each rotation . in summary , the reynolds stress tensor is projected to six physically interpretable , galilean invariant quantities representing the magnitude ( @xmath0 ) , shape ( @xmath13 , @xmath14 ) , and orientation ( @xmath120 , @xmath121 , @xmath122 ) . they are collectively denoted as @xmath7 . the truths of these quantities can be written as baseline rans predictions corrected by the corresponding discrepancy terms , i.e. , [ eq : delta ] @xmath123 the discrepancies ( @xmath124 , @xmath125 , @xmath126 , @xmath127 , @xmath128 , @xmath129 , denoted as @xmath130 with @xmath131 ) in the six projections of the reynolds stress tensor are responses of the regression functions . we utilize data consisting of pairs of @xmath132 from training flow(s ) to construct the functions @xmath133 . it is assumed that the discrepancies in six quantities @xmath6 are independent , and thus separate functions are built for each of them . this simplification is along the same lines as that made in previous works @xcite . with the input ( mean flow features @xmath12 ) and responses ( reynolds stress discrepancies @xmath134 ) identified above , a method is needed to construct regression functions from training data and to make predictions based on these functions . supervised machine learning consists of a wide variety of such methods including k - nearest neighbors @xcite , linear regression and its variants ( e.g. , lasso ) @xcite , gaussian processes @xcite , tree - based methods ( decision trees , random forests , bagging ) @xcite , neural networks @xcite , and support vector machine @xcite , among others . a major consideration in choosing the regression method is the high dimensionality of the feature space , which is typically ten or higher in our application . the curse of dimensionality makes such methods as k - nearest neighbors , linear regression , and gaussian processes not suitable . secondary considerations , which we believe are also important for turbulence modeling applications , are the capability to provide predictions with quantified uncertainties as well as physical insights ( e.g. , on the importance of each of the features and their interactions ) . after evaluating a number of existing machine learning techniques in light of these criteria , we identified _ random forests _ @xcite as the optimal approach for our purposes , which is an ensemble learning technique based on decision trees . in simple decision tree learning , a tree - like model is built to predict the response variable by learning simple if - then - else decision rules from the training data . decision trees have the advantage of being easy to interpret ( e.g. , via visualization ) and implement . they are also computationally cheap . however , they tend to overfit the data and lack robustness . that is , a small change in the training data can result in large changes in the built model and its predictions . random forests learning is an ensemble learning technique proposed by ho @xcite and briemann @xcite that overcomes these shortcomings of simple decision trees . since these techniques are generally not familiar to readers in the fluid dynamics community , here we use an illustrative example in the context of turbulence modeling to explain the algorithm . a simple decision tree model is illustrated in fig . [ fig : tree - schematic ] . for clarity we consider an input with only two features : pressure gradient @xmath135 ( normalized and projected to the streamline tangential ) and wall distance based reynolds number @xmath136 , as defined in table [ tab : feature ] . it can be also interpreted as wall distance in viscous unit . the response is the discrepancy @xmath126 of the vertical coordinate in the barycentric triangle of the rans - predicted reynolds stress ( see fig . [ fig : bary ] ) . during the training process , the feature space is _ successively _ divided into a number of boxes ( leafs ) based on the training data ( shown as points in the @xmath135@xmath137 plane in fig . [ fig : tree - schematic]a ) . in the simplest decision tree model used for regression , the feature space is stratified with the objective of minimizing the total in - leaf variances of the responses at each step , a strategy that is referred to as greedy algorithm . after the stratification , a constant prediction model is built on each leaf . when predicting the response @xmath126 for a given feature vector @xmath12 , the constructed tree model in fig . [ fig : tree - schematic]b is traversed to identify the leaf where @xmath12 is located , and the mean response on the leaf is taken as the prediction @xmath138 . the tree model has a clear physical interpretation in the context of turbulence modeling . for example , it is well known that a standard isotropic eddy viscosity model has the largest discrepancy when predicting anisotropy in the viscous sublayer ( @xmath139 ) . this is because the truth is located on the bottom , corresponding to a combination of one- or two - component turbulence , while a typical isotropic eddy viscosity model would predict an isotropic state located on the top vertex ( see fig . [ fig : bary ] ) . in contrast , far away from the wall within the outer layer ( @xmath140 ) , the rans - predicted anisotropy is rather satisfactory . therefore , the first two branches divide the space to three regions based on the feature @xmath137 : outer layer ( region 1 ) , viscous sublayer ( region 2 ) , and buffer layer ( regions 3 and 4 ) . in the buffer layer the pressure gradient plays a more important role than in the outer and viscous layers . larger pressure gradients correspond to larger discrepancies , which can be explained by the fact that favorable pressure gradients ( negative @xmath135 values ) tend to thicken the viscous sublayer @xcite , which leads to larger discrepancies in @xmath14 . therefore , a further division splits the buffer layer states to two regions in the feature space , i.e. , those with strong ( region 3 ) and mild ( region 4 ) pressure gradients . a simple regression tree model described above tends to overfit for high dimensional input space , i.e. , yielding models that explain the training data very well but predict poorly for unseen data . in general the decision trees do not have the same level of predictive accuracy as other modern regression methods . however , by aggregating a large number of trees ( ideally with minimum correlation ) , the predictive performance can be significantly improved and , the overfitting can be largely avoided . in random forests an ensemble of trees is built with bootstrap samples ( i.e. , sampling with replacement ) drawn from the training data @xcite . moreover , when building each tree , it utilizes only a subset of @xmath141 randomly chosen features among the @xmath142 features , which reduces the correlation among the trees in the ensemble and thus decreases the bias of the ensemble prediction . random forest regression is a modern machine learning method with predictive performance comparable to other state - of - the - art techniques @xcite . in decision tree models the maximum depth of trees must be limited ( e.g. , by pruning the branches far from the root ) to ensure a sufficient number of training point ( e.g. , 5 ) on each node . in contrast , in random forests , one can build each tree to its maximum depth by successive splitting the nodes until only one training data point remains on each leaf . while each individual tree built in this manner may suffer from overfitting and has large prediction variances , the use of ensemble largely avoids both problems . moreover , random forest regression is simple to use with only two free parameters , i.e. , the number @xmath143 of trees in the ensemble and the number @xmath144 of selected features . in this work we used an ensemble of @xmath145 trees and the a subset of features ( i.e. , @xmath146 ) to build each tree . as a standard practice in statistical modeling , we performed cross - validations to optimize these parameters and performed sensitivity analysis to ensure that the predictions are not sensitive to the parameter choices . almost all industrial flows involve some characteristics ( e.g. , strong pressure gradient , streamline curvature , and separation ) that break the equilibrium assumption of rans model . therefore , we have these challenges in mind when developing the data - driven approach . in this study , we focus on the cases where training and test flows have similar characteristics . specifically , we evaluate the proposed method on two classes of flows : ( 1 ) fully developed turbulent flows in a square duct at various reynolds numbers and ( 2 ) flows with massive separations . the flow in a square duct at reynolds number @xmath147 and the flow in a channel with periodic hills at reynolds number @xmath148 are chosen as the prediction ( test ) flows for the respective flow classes . the square duct flow has an in - plane secondary flow pattern induced by the normal stress imbalance , while the periodic - hill flow features a recirculation bubble , non - parallel shear layer and mean flow curvature . all these characteristics are known to pose challenges for rans based turbulence models , and thus large model - form discrepancies exist in the rans - modeled reynolds stresses . in the two test flows , the relative importance of reynolds stress projections to the mean flow prediction are different . the reynolds stress anisotropy plays an important role in obtaining the accurate secondary mean motion in the duct flow @xcite . in contrast , the anisotropy is less important to predict the mean flow in the periodic - hill case , where the turbulent shear stress component is more essential to obtain an accurate mean velocity field @xcite . therefore , we use these two types of flows to highlight the improvements in the different reynolds stress components that are important for the predictions of qois in the respective flow classes . in both cases , all rans simulations are performed in an open - source cfd platform , openfoam , using a built - in incompressible flow solver ` simplefoam ` @xcite . mesh convergence studies have been performed . the fully developed turbulent flow in a square duct is a challenging case for rans - based turbulence models , since the secondary mean motion can not be captured by linear eddy viscosity models ( e.g. , @xmath0@xmath1 , @xmath0@xmath2 ) , and even the reynolds stress transport models ( rstm ) can not predict it well @xcite . in this test , we aim to improve the rans - modeled reynolds stresses of the duct flow at reynold number @xmath147 by using the proposed piml approach . the training data are obtained from dns simulations @xcite of the duct flows in the same geometry but at lower reynolds numbers @xmath149 and @xmath150 . the dns data of the prediction flow ( @xmath147 ) are reserved for comparison and are not used for training . coordinate represents the streamwise direction . secondary flows induced by reynolds stress imbalance exist in the @xmath115@xmath111 plane . panel ( b ) shows that the computational domain covers a quarter of the cross - section of the physical domain . this is due to the symmetry of the mean flow in both @xmath115 and @xmath111 directions as shown in panel ( c).,scaledwidth=80.0% ] the geometry of this flow case is shown in fig . [ fig : domain_duct ] . the reynolds number is based on the edge length d of the square duct and the bulk velocity @xmath151 . all lengths presented below are normalized by @xmath152 . the baseline rans simulations are performed for all training and test flows . the purpose is twofold : to obtain the mean flow feature fields @xmath22 as inputs and to obtain the discrepancies of reynolds stress by comparing with the dns data . to enable the comparison , the high - fidelity data are interpolated onto the mesh of rans simulation . the launder - gibson rstm @xcite is adopted to perform the baseline simulations , since all the linear eddy viscosity models are not able to capture the mean flow features of the secondary motions . the @xmath153 of the first cell center is kept less than 1 and thus no wall model is applied . as indicated in fig . [ fig : domain_duct ] , only one quadrant of the physical domain is simulated owing to the symmetry of the mean flow with respect to the centerlines along @xmath115- and @xmath111-axes . no - slip boundary condition is applied on the walls , and symmetry boundary condition is applied on the symmetry planes . we first investigate the prediction performance on the reynolds stress anisotropy tensor , since its accuracy is important to capture the secondary flow . figure [ fig : bayre ] shows piml - corrected anisotropy in barycentric triangle compared with baseline and dns results . the comparisons are performed on two representative lines at @xmath154 and @xmath155 on the in - plane cross section ( fig . [ fig : domain_duct]b ) . the two lines are indicated in the insets on the upper left corner of each panel . the arrows denote the order of sample points plotted in the triangle , which is from the bottom wall to the outer layer . the general trends of spatial variations of the dns reynolds stress anisotropies are similar on both lines . that is , from the wall to the outer layer , the reynolds stress starts from the two - component limiting states ( bottom edge of the triangle ) toward three - component anisotropic states ( middle area of the triangle ) . this trend is captured by the baseline rstm to some extent , especially in the regions away from the wall . however , significant discrepancies still can be observed in the near - wall region . very close to the wall , the dns reynolds stress is nearly the two - component limiting state . this is because the velocity fluctuations in the wall - normal direction are suppressed by the blocking of the bottom wall . moreover , before approaching three - component anisotropic states , the dns - predicted anisotropy first moves toward the one - component state ( 1c ) as away from the wall . in contrast , the rans - predicted anisotropy near the wall is closer to the two - component isotropic state ( 2c - i ) , and it approaches toward the three - component anisotropic state directly . therefore , in the near - wall region there are large discrepancies between the rans predicted reynolds stress anisotropy and the dns result , particularly in the horizontal coordinate @xmath13 . by correcting the baseline rstm results with the trained discrepancy function , the predicted anisotropy of reynolds stress is significantly improved . for both lines , the predicted anisotropy ( circles ) agrees well with the dns results ( squares ) . especially on the line @xmath156 , the piml - predicted anisotropy is almost identical to the dns data . significant improvement of the piml - predicted anisotropy can be seen from the barycentric maps shown in fig . [ fig : bayre ] . similar improvements have also been demonstrated in the other physical projections ( tke and orientations ) of the piml - corrected reynolds stresses . therefore , it is expected that the reynolds stress tensor components should be also improved over the rstm baseline . and ( b ) @xmath157 of corrected reynolds stress with the discrepancy model . the profiles are shown at four streamwise locations @xmath158 and @xmath159 . corresponding dns and baseline ( rstm ) results are also plotted for comparison.,title="fig:",scaledwidth=40.0% ] + in the six tensor components , two normal stress components @xmath160 and @xmath157 are among the most important ones to the mean velocity field since the normal stress imbalance ( @xmath161 ) is the driving force of the secondary flow @xcite . figures [ fig : tau_duct]a and [ fig : tau_duct]b show the profiles of normal components @xmath160 and @xmath157 of the reynolds stress reconstructed from the piml - corrected physical projections . corresponding baseline ( rstm ) and dns results are also plotted for comparison . both @xmath160 and @xmath157 are overestimated by the rstm over the entire domain . the discrepancy of the rstm - predicted @xmath160 is large near the wall and decreases when moving away from the wall . in contrast , @xmath157 is significantly overestimated far from the wall but the discrepancy decreases toward the wall . as a results , the rstm - predicted normal stress imbalance is pronouncedly inaccurate , which leads to unreliable secondary mean flow motion . as expected , the piml predictions nearly overlap with the dns results for both @xmath160 and @xmath157 and show considerable improvements over the rstm baseline . in fact , the improvements are observed in all the tensor components , which are omitted here for brevity . the results shown above demonstrate excellent performance of the proposed piml framework by using rstm as the baseline . the turbulent flow in a channel with periodic hills is another challenging case for rans models due to the massive flow separations in leeward of the hill . here , we examine two training scenarios with increasing difficulty levels . in the first scenario the training flows have the same geometry as the test ( prediction ) flow but are different in reynolds numbers . in the second scenario the training flows differ from the prediction case not only in reynolds numbers but also in geometry . p2.5 cm | p8.0 cm | p4.5 cm training flow scenario & training flow & symbol & high fidelity data + & periodic hills , re = 1400 ( ph1400 ) & dns by breuer et al . @xcite + & periodic hills , re = 5600 ( ph5600 ) & dns by breuer et al . @xcite + & wavy channel , re = 360 ( wc360 ) & dns by maa et al . @xcite + & curved backward facing step , re = 13200 ( cs13200 ) & les by bentaleb et al . @xcite + four training flows with dns / les data to build random forest regressors are summarized in table [ tab : database ] . in the first scenario two flows ph1400 and ph5600 are used for training , both of which are flows over periodic hills ( same in geometry ) at @xmath162 and @xmath163 ( different in reynolds numbers ) , respectively . for the second scenario , the training data are obtained from two different flows : one in a channel with a wavy bottom wall at @xmath164 and one over a curved backward facing step at @xmath165 , indicated as flows wc360 and cs13200 , respectively . + + a schematic of the flow geometry and rans - predicted velocity contour for each case are presented in fig . [ fig : flowgeo ] . the dimensions of each case are normalized with the respective hill heights @xmath55 . although the geometries of the training flows are different , all three flows share a similar characteristic as the test flow , i.e. , separation on the leeward side of the hill or step . however , the separation bubbles are different in sizes and shapes . the flow over periodic hills has a stronger separation compared to the other two due to the steeper slope of the hill . relatively mild separation can be observed in the flow over the wavy channel . for all cases , both high - fidelity data and rans - predicted results are available . the high - fidelity data are obtained from dns or resolved les simulations , which have been reported in literature ( see references in table . [ tab : database ] ) . the dns data for flows ph1400 and ph5600 are only available on vertical lines at eight streamwise locations @xmath166 . on the other hand , full - field high - fidelity results are available for flows wc360 and cs13200 , but only the lower part of the channel is adequately resolved . since the separated flow is of interest in this study , only the data in the separation region ( i.e. , region below @xmath167 ) are included . in this test , the performance of the proposed piml framework is evaluated on standard rans models . specifically , the baseline rans predictions are obtained by using the two - equation launder - sharma @xmath0@xmath1 model @xcite . the reason for choosing standard turbulence models here is because of two considerations . first , the standard rans models are the dominant tools for industrial cfd applications , while other sophisticated rans models have been rarely used . therefore , it is more significant to improve the widely used standard rans models . second , we understand that improvement of the reynolds stresses starting from a standard rans model is challenging . nonetheless , this challenging scenario also can better explore the capability of machine learning approach . the functional forms of discrepancies in the six physical projections of reynolds stress are learned from the training flows as mentioned in section [ sec : result : separation : setup ] and are used to correct the rans - predicted reynolds stress field of the test flow ( ph10595 ) . however , since the baseline rans model used in this case is the standard eddy viscosity model , the reynolds stress anisotropy can not be accurately predicted . therefore , the baseline rans - predicted anisotropy is unphysical and is significantly different from the dns result ( see fig . [ fig : bary ] ) . nonetheless , after the correction by using the discrepancy function learned from the training flows , the anisotropy of the test flow shows an excellent agreement with the dns results @xcite . the improvements are observed in the both training scenarios i and ii , demonstrating that the discrepancy function even in the standard rans - predicted anisotropy does exist and can be learned from the closely related flows based on the mean flow features @xmath12 . as mentioned above , in the periodic - hill flow , the correctness of reynolds stress anisotropy is of little consequence to the prediction of the mean velocity , and the correct shear stress component and magnitude of the reynolds stress are most important to obtain an accurate mean flow field . therefore , the anisotropy prediction results are omitted here , and only the turbulence kinetic energy ( tke ) and shear stress component of the piml - corrected reynolds stress are presented and discussed in detail . . corresponding baseline and dns results are also plotted for comparison . the hill profile is vertically exaggerated by a factor of 1.3.,scaledwidth=80.0% ] the comparison of the tke profiles of the baseline , dns , and piml - predicted results in the training scenario i are shown in fig . [ fig : kre ] . the tke predicted by the baseline rans model has notable discrepancies compared to the dns result , particularly in the region with non - parallel free shear flow ( @xmath168 to @xmath169 ) . the poor performance of rans model in such region is typical in these flows @xcite . the rans model underestimates the turbulence intensity along the free shear at @xmath170 , especially near the leeward side of the hill ( @xmath171 to @xmath172 ) . in the upper channel ( @xmath173 to @xmath174 ) , the dns tke is slightly smaller than the baseline rans prediction . the profiles of tke corrected by the piml - predicted discrepancy @xmath124 are significantly improved . the peaks along the streamwise free shear in the dns profiles are well captured in the corrected results with the random forest prediction . it can be seen that the predicted tke profiles ( solid lines ) nearly overlap with the dns results ( dashed lines ) . this clearly indicates that the tke discrepancies can be learned from the data of the training flows . . corresponding baseline and dns results are also plotted for comparison . the hill profile is vertically exaggerated by a factor of 1.3.,scaledwidth=80.0% ] it is also of interest to investigate the tensor components @xmath175 of reynolds stress , which are more relevant for predicting velocities and other qois of the flow fields . for the plane shear flows , the turbulent shear stress @xmath176 is important to predict the velocity field . figure [ fig : taure ] compares the turbulence shear component @xmath176 of predicted reynolds stress with the dns . as expected , significant improvements are observed compared to the baseline results , which underestimate the peak of @xmath176 on the leeward hill side but overestimate it on the windward hill side . as shown in fig . [ fig : taure ] , the profiles of predicted @xmath176 agree well with the dns results . the results above demonstrate that the discrepancy function of reynolds stress in its physical projections ( i.e. , magnitude , shape , and orientation ) trained from the flows at re = 2800 and 5600 can be used to predict the reynolds stress field of the flow at re = 10595 . significant improvements are observed in the predicted reynolds stress compared to the baseline rans results . although in this scenario the training and test flows are quite similar ( with the same geometry ) , and the success of extrapolation has been demonstrated in physical space by wu et al . @xcite , it should not be taken for granted that the accurate prediction is also guaranteed in feature space . since the regressions are performed in the ten - dimensional feature space and there is no direct reference to the physical coordinate , the success is not trivially expected _ a priori_. we investigate a more challenging scenario where the training flows have different geometries from the prediction case . this scenario is also more realistic in the context of using rans simulation to support engineering design and analysis . specifically , the data are more likely to be available for a few flows with specific reynolds numbers and geometries , but predictions are needed for the similar flows yet at different reynolds numbers and with modified geometries . . corresponding baseline and dns results are also plotted for comparison . the hill profile is vertically exaggerated by a factor of 2.4 . , scaledwidth=90.0% ] the comparison of the tke profiles on eight lines is shown in fig . [ fig : kgeo ] . note that only the domain below @xmath167 is investigated due to the lack of reliable high - fidelity training data in the upper channel region . this inadequacy of data quality can be exacerbated when the reynolds stress is decomposed to its physical projections . moreover , the flow separation is the phenomenon of concern in this study , and thus we only focus on the recirculation region . in fig . [ fig : kgeo ] , the random forest predicted tke ( solid lines ) is significantly improved over the baseline results ( dotted lines ) and better agrees with the dns profiles ( dash - dotted lines ) . the agreement is particularly good in the region from the center of recirculation bubble ( @xmath177 ) to the beginning of flow contraction ( @xmath178 ) . nonetheless , the piml - predicted tke does not show any improvement and even deteriorates compared to the baseline results near the windward side of the hill ( @xmath179 ) , where the flow starts to be contracted . as shown in fig . [ fig : kgeo ] , the predicted tke is markedly overestimated at @xmath180 . this is because the flow features in the contraction region ( @xmath179 ) are not supported in the training set , since the contracted flow does not exist in the training flow cs13200 ( fig . [ fig : flowgeo]c ) and is much weaker in the training flow wc360 ( fig . [ fig : flowgeo]b ) due to the mild slope of wavy bottom in this geometry . . corresponding baseline and dns results are also plotted for comparison . the hill profile is vertically exaggerated by a factor of 2.4 . , scaledwidth=90.0% ] finally , we compare the predicted turbulent shear stress @xmath176 with the dns profiles in fig . [ fig : taugeo ] . similar to the results of tke , the piml - predicted turbulent shear stress @xmath176 shows notable improvements in the recirculation region . however , deterioration occurs in the flow contraction region . at @xmath181 and @xmath182 , the magnitudes of turbulent shear stresses are overestimated with the correction based on the predicted discrepancies . this is consistent with the results observed in physical projections of reynolds stress . such a small region with abnormal reynolds stress corrections ( artificial peaks or bumps ) can introduce large errors to the velocity predictions . in general , the physical projections ( i.e. , magnitude , shape , and orientation ) of reynolds stress corrected by random forest predicted discrepancies are still significantly improved with the training flows in different geometries ( wc360 and cs13200 ) . the reynolds stress is markedly improved in the separated flow region , but not in the contracted flow region . this is because the features in training flows can not well support the predicted flow , and thus more extrapolations are expected . although the improvement is less significant compared to that in the scenario , the random forest predictions in this more realistic scenario are still satisfactory , demonstrating the merits of the proposed piml framework . in addition to the predictive capability of the regression model , it is also important to interpret the functional relation between the mean flow features and the discrepancies of the rans modeled reynolds stresses . for example , it is useful to find the most important features to the reynolds stress discrepancy in each of its physical projection ( i.e. , magnitude @xmath0 , shape @xmath183 , and orientation @xmath15 ) , and how each of these features impacts the regression response . identification of such correlation or causal relationship enables modelers to improve the rans turbulence models . the random forest regressor used in the proposed piml framework can also shed light on this issue by calculating the feature importance , which is a measure to evaluate the relative importance of a feature variable for predicting response variables @xcite . the bar plots of the importances of feature vector @xmath12 with respect to the discrepancies @xmath126 and @xmath184 are shown in figs . [ fig : import]a and [ fig : import]b , respectively . for discrepancy @xmath126 in the anisotropy , feature @xmath45 ( i.e. , wall - distance based reynolds number @xmath137 ) is the most important one . as discussed in section [ sec : feature ] , @xmath137 is the wall distance normalized by the approximate viscous unit . therefore , the result of feature importance is consistent with the piml prediction , which have shown that the discrepancy @xmath126 is notably dependent on the distance away from the wall @xcite . figure [ fig : import]b shows that the most important feature for predicting discrepancy @xmath184 of turbulence kinetic energy is feature @xmath51 , turbulence intensity . it is demonstrated that random forest used in the proposed framework can interpret the relationship between the features and the response to a certain extent , although the feature importance has its limitation due to bias introduced under certain conditions @xcite . in the machine learning community , improving interpretability of random forest is an active research topic , e.g. , several improvements of the importance measure have been proposed @xcite . moreover , in addition to calculating the feature importance , it is also helpful to examine the interactions among features , which have important implications for the interpretation of the regression models . as the base learner in random forest is a decision tree , which can capture the feature interactions , it is possible to further investigate the interacting relationship among mean flow variables . breiman et al . have studied feature interaction in random forest method @xcite , but more research is still ongoing . a better understanding of the physics behind the regression model for reynolds stress discrepancies has a profound implication to rans turbulence modeling . therefore , to explore the correlation or causal relationship between the mean flow features and the discrepancies of rans modeled reynolds stress is an important and promising extension of the proposed framework . the objective of the proposed framework is to improve the baseline rans - predicted reynolds stresses of a flow where high - fidelity ( e.g. , dns , les , experimental ) data are not available . the main novelty lies in using machine learning techniques to find the functional forms of reynolds stress discrepancies with respect to mean flow features by learning from the existing offline database of the closely related flows . numerical simulation results have demonstrated the feasibility and merits of the framework . moreover , the excellent performance of the piml predicted reynolds stress in not only the anisotropy but also in the tke and turbulent shear stress shows the fact that reynolds stress discrepancies can be extrapolated even to complex flows sharing similar characteristics . this finding is noteworthy by itself . the improvement of the rans - predicted reynolds stress is considered a viable and promising path toward obtaining better predictions of velocities and other quantities of interest . however , due to a few limitations of the current framework , the improvement of the propagated velocities from the corrected reynolds stress field can not be guaranteed . a small region with abnormal reynolds stress corrections ( e.g. , non - smoothness or artificial peaks ) can introduce large errors to the velocity predictions . for example , the small wave - number variations in reynolds stresses are visible in fig . [ fig : taugeo ] . these fluctuations , despite being small in amplitude , can lead to abnormal behaviors in the divergence term and thus in the predicted velocities . these abnormal predictions of reynolds stress corrections can be caused by several factors . first , the features in certain regions of the prediction flow may not be well supported in the training flows , e.g. the contraction region of periodic - hill flow mentioned in sec . [ sec : result : separation ] . second , the random forest regression used here only provides pointwise estimations but can not consider the spatial information of the reynolds stress field . therefore , the smoothness of the prediction can not be guaranteed . finally , although the input feature space is constructed based on physical reasoning , it is possible that the input features are not rich enough , and thus the randomness in the ensemble of the trained decision trees is significant . in this work , we proposed a physics - informed machine learning approach to reconstruct reynolds stresses modeling discrepancies by utilizing dns databases of training flows sharing similar characteristics as the flow to be predicted . for this purpose , we formulated discrepancy of reynolds stresses ( or more precisely its magnitude and the shape and orientation of the anisotropy ) as target functions of mean flow features and used modern machine learning techniques based on random forest regression to learn the functions . the obtained functions are then used to predict reynolds stress discrepancies in new flows . to evaluate the performance of the proposed approach , the method is tested by two classes of flows : ( 1 ) fully developed turbulent flows in a square duct at various reynolds numbers and ( 2 ) flows with massive separations . in the separated flows , two training flow scenarios of increasing difficulties are considered : in the less challenging scenario , data from two flows in the same periodic hill geometry at lower reynolds numbers ( @xmath185 and 5600 ) are used for training . in a more challenging scenario , the training data come from separated flows in different geometries ( wavy channel and curved backward facing step ) . in all test cases the corrected reynolds stresses are significantly improved compared to the baseline rans predictions , demonstrating the merits of the proposed approach . in the scenario , where the training flows and the prediction flow have different geometries , the improvement is not as drastic as in the the scenario with the same geometry . this is expected since the prediction involves more extrapolations in the feature space for this more challenging scenario . in other words , compared to the first scenario where the training and prediction flows have identical geometry , the prediction flow is less `` similar '' to the training flows in this scenario . the extent to which the training and prediction flows are `` similar '' to each other can be assessed _ a priori _ based on their respective rans predicted mean flow field , and methods for such assessment are presented in companion publications @xcite . as the inaccuracy in modeled reynolds stresses is the dominant source of model - form uncertainty in rans simulations , the proposed method for improving rans - predicted reynolds stresses is an important step towards the goal of enabling predictive capabilities of rans models . moreover , the random forests regression technique adopted in this work can provide physical insights regarding the relative importance of mean flow features that contributed to the discrepancies in the rans predicted reynolds stresses . this information can be used to assist future model development in that developers can devise models that are aware of and correctly respond to these flow features . however , a number of challenges need to be tackled before the improved reynolds stresses can be used to predict more accurate quantities of interests that are needed in engineering design ( e.g. , draft and lift coefficients ) . this topic will be investigated in future research . we thank dr . julia ling of sandia national laboratories and dr . eric g. paterson of virginia tech for helpful discussions during this work . we also thank the anonymous reviewers for their comments , which helped improving the quality and clarity of the manuscript . e. dow , q. wang , quantification of structural uncertainties in the @xmath0@xmath2 turbulence model , in : 52nd aiaa / asme / asce / ahs / asc structures , structural dynamics and materials conference , aiaa , denver , colorado , 2011 , aiaa paper , 2011 - 1762 . h. xiao , j .- l . wu , j .- x . wang , r. sun , c. roy , quantifying and reducing model - form uncertainties in reynolds - averaged navier stokes simulations : a data - driven , physics - informed bayesian approach , journal of computational physics 324 ( 2016 ) 115136 . c. gorle , m. emory , g. iaccarino , rans modeling of turbulent mixing for a jet in supersonic cross flow : model evaluation and uncertainty quantification , in : ichmt digital library online , begel house inc . , 2012 . f. billard , development of a robust elliptic - blending turbulence model for near - wall , separated and buoyant flows . , thesis , school of mechanical aerospace and civil engineering , the university of manchester . , manchester , uk ( 2011 ) . h. xiao , j .- l . wu , j .- x . wang , e. g. paterson , physics - informed machine learning for predictive turbulence modeling : progress and perspectives , in proceedings of the 2017 aiaa scitech , in press ( 2017 ) . a. dobra , j. gehrke , bias correction in classification tree construction , in : proceedings of the eighteenth international conference on machine learning , morgan kaufmann publishers inc . , 2001 , pp .
turbulence modeling is a critical component in numerical simulations of industrial flows based on reynolds - averaged navier - stokes ( rans ) equations . however , after decades of efforts in the turbulence modeling community , universally applicable rans models with predictive capabilities are still lacking . large discrepancies in the rans - modeled reynolds stresses are the main source that limits the predictive accuracy of rans models . identifying these discrepancies is of significance to possibly improve the rans modeling . in this work , we propose a data - driven , physics - informed machine learning approach for reconstructing discrepancies in rans modeled reynolds stresses . the discrepancies are formulated as functions of the mean flow features . by using a modern machine learning technique based on random forests , the discrepancy functions are trained by existing dns databases and then used to predict reynolds stress discrepancies in different flows where data are not available . the proposed method is evaluated by two classes of flows : ( 1 ) fully developed turbulent flows in a square duct at various reynolds numbers and ( 2 ) flows with massive separations . in separated flows , two training flow scenarios of increasing difficulties are considered : ( 1 ) the flow in the same periodic hills geometry yet at a lower reynolds number , and ( 2 ) the flow in a different hill geometry with a similar recirculation zone . excellent predictive performances were observed in both scenarios , demonstrating the merits of the proposed method . model - form uncertainty , turbulence modeling , reynolds - averaged navier stokes equations , boussinesq assumption , data - driven modeling , machine learning
anterior cervical and lumbar spine surgery is one of the most commonly performed spinal procedures . anterior cervical discectomy and fusion ( acdf ) is an established surgical procedure for the management of patients with cervical radiculopathy and myelopathy secondary to degenerative disc disease and spondylosis2 ) . various complications related to anterior cervical spine surgery including postoperative recurrent laryngeal nerve palsy , horner syndrome , pharyngeal / esophageal laceration and vessel injury have been reported8 ) . anterior lumbar surgery is also commonly used for the treatment of degenerative disc disease , spondylolisthesis , tumor , infection and fracture . this approach has many advantages including excellent exposure of the operation field , a thorough discectomy can be performed , and no disruption of the paravertebral muscle and ligament . anterior lumbar surgery - related complications reported in the literature have been mainly focused on vascular injury , infection and gastrointestinal issues4,21 ) . sympathetic dysfunction is one of the possible complications of anterior spine surgery ; however , it has been underestimated . our two patients presented with dysesthetic pain in the upper and lower extremities soon after cervical and lumbar surgery using an anterior approach , respectively . their pain was dramatically relieved after a block of the stellate ganglion and lumbar sympathetic ganglion , respectively . only few literatures describe the rare occurrence of sympathetic dysfunction related pain developing after anterior spine surgery and the treatment13,22 ) . we aimed to report two successful experiences of treating dysesthetic pain occurring immediately after anterior cervical and lumbar surgery by using a sympathetic block and to describe the sympathetically maintained pain ( smp ) as one of the important causes of early postoperative pain . a 43-year - old man with a 3-month history of burning dysesthetic pain and tightness in both upper limbs but mainly in the right upper extremity , which developed after three cervical spine operations , was referred to our hospital with opioid , gabapentin and amitriptyline medications . five months prior to admission , he underwent 6-mm artificial disc replacement at the c6/7 level through a left anterior approach because of radiculopathy of the right c7 dermatome due to a herniated intervertebral disc at the right paracentral and foraminal region of c6/7 ( fig . 1 ) . after the surgery his pain was reduced , however , similar pain recurred a month after the operation . two months after the first operation , he underwent c5/6 anterior cervical discectomy through a left acdf after a diagnostic right c5/6 transforaminal epidural block , with relief of symptoms . on the day following the second operation , he started to experience an unexpected burning and stabbing pain that he rated as 9/10 on a numeric rating scale ( nrs ) in both upper extremities below the elbow , especially in the right hand . plain radiographs and mri of the cervical spine obtained immediately after the procedure showed no evidence of soft tissue hematoma or mechanical failure of the implanted instrumentation ( fig . 2 ) . finally , ten days after the second operation , he underwent exploration and replacement of the 6-mm height artificial disc with a 5.25-mm height disc at c6/7 due to a suspicion of a possible stretching injury of the cervical spinal nerve . unfortunately , even after the surgery , his severe pain and tightness persisted . he has begun to take opioid medication and underwent a bilateral c5/6 and c6/7 transforaminal epidural block , right suprascapular nerve block and trigger point injections , but with no effect . at initial evaluation in our hospital , he presented with chest discomfort , mild hoarseness , tightness and insomnia , neck pain and severe dysesthetic pain in a non - dermatomal pattern in the right upper extremities , at the level of 9/10 , by nrs . laryngoscopic examination by an otolaryngologist revealed slightly decreased mobility of vocal cords on the left side , which indicated a clinical diagnosis of injury of the left recurrent laryngeal nerve . we performed a right stellate ganglion block ( sgb ) with 5 ml of 0.5% mepivacaine . after the procedure , his pain and tightness of the right arm reduced to 4/10 on the nrs . he underwent serial six right sgbs for two weeks , with gabapentin and amitriptyline medications . after this , his pain reduced dramatically to 0/10 on the nrs . during the one - year following the treatment , the patient reported three intermittent episodes of mild right arm pain , but overall the pain has been satisfactorily controlled with sgb . a 69-year - old woman with a 2-month history of right lateral calf and foot pain she had a history of undergoing anterior lumbar interbody fusion ( alif ) through a left retroperitoneal approach , decompressive laminectomy and posterior fusion from l3 to s1 due to pain in the lower back and both lower extremities two months before presenting to our hospital . the preoperative pain was especially severe on the left due to a herniated intervertebral disc at the left foraminal region of l5/s1 and degenerative spondylolisthesis at the l3/4 and l4/5 levels ( fig . however , she began experiencing a severe unexpected pain 9/10 on the nrs in the right lower extremity below the knee and complained of a cold sensation of the right foot without any change of great toe dorsiflexion following the last operation . the right l3/4 , l4/5 , and l5/s1 transforaminal epidural block did not reduce her pain significantly . a doppler sonography of both lower extremities that was done to rule out deep vein thrombus was normal . two weeks after the first operation , she received right l4/5 and l5/s1 facetectomy and decompression surgery from the right l4 to s1 nerve root . her pain and dysethesia of the right calf and foot at the level of 9/10 on the nrs persisted . she underwent subsequent right sacroiliac joint injection , right l4/5 , l5/s1 transforaminal epidural block and percutaneous epidural adhesiolysis , especially focused on the right l5/s1 foramen ( fig . 4a ) , but this also had no effect . finally , she underwent additional decompression surgery at the right l5/s1 extraforaminal region ( fig . unfortunately , the pain was not relieved , and the patient was referred to our hospital . at this time , the pain was not controlled despite being on a pain management regimen consisting of opioid , gabapentin and amitriptyline medications . on arrival at our hospital , she complained of dysesthetic pain in the right lower extremity below the knee , especially her foot , in a non - dermatomal pattern of an intensity level of 9/10 on the nrs . we decided to perform right lumbar sympathetic block ( lsb ) at l3 with 10 ml of 0.36% ropivacaine ( fig . she reported reduced pain from 9/10 to 4/10 on the nrs for 5 hours following the procedure . three days after the lsb , we performed radiofrequency lesioning of the right lumbar sympathetic chain at the l2 and l3 levels . her pain gradually subsided and she reported prolonged warmth in her right foot . during the six - months following the treatment , she reported no recurrence of her pain without opioid , gabapentin and amitriptyline medications . a 43-year - old man with a 3-month history of burning dysesthetic pain and tightness in both upper limbs but mainly in the right upper extremity , which developed after three cervical spine operations , was referred to our hospital with opioid , gabapentin and amitriptyline medications . five months prior to admission , he underwent 6-mm artificial disc replacement at the c6/7 level through a left anterior approach because of radiculopathy of the right c7 dermatome due to a herniated intervertebral disc at the right paracentral and foraminal region of c6/7 ( fig . 1 ) . after the surgery his pain was reduced , however , similar pain recurred a month after the operation . two months after the first operation , he underwent c5/6 anterior cervical discectomy through a left acdf after a diagnostic right c5/6 transforaminal epidural block , with relief of symptoms . on the day following the second operation , he started to experience an unexpected burning and stabbing pain that he rated as 9/10 on a numeric rating scale ( nrs ) in both upper extremities below the elbow , especially in the right hand . plain radiographs and mri of the cervical spine obtained immediately after the procedure showed no evidence of soft tissue hematoma or mechanical failure of the implanted instrumentation ( fig . 2 ) . finally , ten days after the second operation , he underwent exploration and replacement of the 6-mm height artificial disc with a 5.25-mm height disc at c6/7 due to a suspicion of a possible stretching injury of the cervical spinal nerve . unfortunately , even after the surgery , his severe pain and tightness persisted . he has begun to take opioid medication and underwent a bilateral c5/6 and c6/7 transforaminal epidural block , right suprascapular nerve block and trigger point injections , but with no effect . at initial evaluation in our hospital , he presented with chest discomfort , mild hoarseness , tightness and insomnia , neck pain and severe dysesthetic pain in a non - dermatomal pattern in the right upper extremities , at the level of 9/10 , by nrs . laryngoscopic examination by an otolaryngologist revealed slightly decreased mobility of vocal cords on the left side , which indicated a clinical diagnosis of injury of the left recurrent laryngeal nerve . we performed a right stellate ganglion block ( sgb ) with 5 ml of 0.5% mepivacaine . after the procedure , his pain and tightness of the right arm reduced to 4/10 on the nrs . he underwent serial six right sgbs for two weeks , with gabapentin and amitriptyline medications . after this , his pain reduced dramatically to 0/10 on the nrs . during the one - year following the treatment , the patient reported three intermittent episodes of mild right arm pain , but overall the pain has been satisfactorily controlled with sgb . a 69-year - old woman with a 2-month history of right lateral calf and foot pain was referred to our hospital . she had a history of undergoing anterior lumbar interbody fusion ( alif ) through a left retroperitoneal approach , decompressive laminectomy and posterior fusion from l3 to s1 due to pain in the lower back and both lower extremities two months before presenting to our hospital . the preoperative pain was especially severe on the left due to a herniated intervertebral disc at the left foraminal region of l5/s1 and degenerative spondylolisthesis at the l3/4 and l4/5 levels ( fig . however , she began experiencing a severe unexpected pain 9/10 on the nrs in the right lower extremity below the knee and complained of a cold sensation of the right foot without any change of great toe dorsiflexion following the last operation . the right l3/4 , l4/5 , and l5/s1 transforaminal epidural block did not reduce her pain significantly . a doppler sonography of both lower extremities that was done to rule out deep vein thrombus was normal . two weeks after the first operation , she received right l4/5 and l5/s1 facetectomy and decompression surgery from the right l4 to s1 nerve root . her pain and dysethesia of the right calf and foot at the level of 9/10 on the nrs persisted . she underwent subsequent right sacroiliac joint injection , right l4/5 , l5/s1 transforaminal epidural block and percutaneous epidural adhesiolysis , especially focused on the right l5/s1 foramen ( fig . . finally , she underwent additional decompression surgery at the right l5/s1 extraforaminal region ( fig . unfortunately , the pain was not relieved , and the patient was referred to our hospital . at this time , the pain was not controlled despite being on a pain management regimen consisting of opioid , gabapentin and amitriptyline medications . on arrival at our hospital , she complained of dysesthetic pain in the right lower extremity below the knee , especially her foot , in a non - dermatomal pattern of an intensity level of 9/10 on the nrs . we decided to perform right lumbar sympathetic block ( lsb ) at l3 with 10 ml of 0.36% ropivacaine ( fig . she reported reduced pain from 9/10 to 4/10 on the nrs for 5 hours following the procedure . three days after the lsb , we performed radiofrequency lesioning of the right lumbar sympathetic chain at the l2 and l3 levels . her pain gradually subsided and she reported prolonged warmth in her right foot . during the six - months following the treatment , she reported no recurrence of her pain without opioid , gabapentin and amitriptyline medications . the chronic postoperative pain is located in an axial and radicular distribution and may be referred to other regions . the character of the pain can be presented in a somatic or neuropathic pattern . poorly defined and vaguely located pain may be present in a nonphysiologic distribution , and onesti20 ) stated that this sort of pain could be associated with medicolegal and psychosocial issues . our two patients complained of severe dysesthetic pain in the early postoperative periods . in this period , inadequate pain relief by surgery at the wrong level and incomplete decompression , postoperative instability , nerve root irritation by surgical hardware , and damage to the muscle and nerve plexus by improper positioning of the patient during prolonged surgery can be sources of pain20,23 ) . however , these causes usually result in somatic pain in a radicular distribution . on the other hand , our patients presented with pain that had neuropathic features in its nonphysiologic distribution ; the pain occurred in both upper extremities , mainly in the contralateral side of anterior spinal approach , in a patient who had undergone cervical surgery , and below the knee of the contralateral lower extremity in a patient who had undergone the anterior lumbar surgery . furthermore , before referral to our hospital , both patients had already undergone precise interventional pain procedures at the corresponding level as seen in the mri and ct , and additional decompression surgery with no effect . therefore , we concluded that the pain of both patients was attributable to sympathetic dysfunction related to surgery . the cervical sympathetic chain including the stellate ganglion is located on the anterior surface of the longus colli muscle , which is an important landmark on the anterior cervical spine and extends from the anterior tubercle of the atlas to the third thoracic vertebral body1,7 ) . for anterior cervical operations , once the prevertebral fascia is opened and the correct level is confirmed , the longus colli muscles are explored on the contralateral anterior side of the spinal lesion . dissection continues out to the uncinate processes and self - retaining retractors are placed beneath the medial edges of the reflected longus colli muscles12 ) . because of its anatomic location , the cervical sympathetic trunk is at potential risk of injury during the anterior approach to the cervical vertebral bodies5 ) . we regarded the pain to be due to injury of the sympathetic chain of the left side and the resultant relative sympathetic hyperactivity of the right side that had begun since the second operation . the lumbar sympathetic chain lies in extreme close proximity to the anterolateral aspect of the vertebral bodies and disc spaces between t12 and l4 . therefore , it is also extremely vulnerable to injury during anterolateral exposure of the vertebral bodies and some previous articles have noted that sympathetic nerve injury is unavoidable during surgery with an anterior approach23,25 ) . we considered our second patient also experienced her pain due to injury of the sympathetic chain of the left side and the resultant relative sympathetic hyperactivity of the right side since the first operation . sympathetic dysfunction causes temperature variation , paresthesia , dysesthetic pain , discoloration , swelling of the corresponding extremity ( upper versus lower extremities ) , gastrointestinal problems and ejaculatory disturbances in the case of lumbar sympathetic dysfunction22 ) . it has been reported that most patients have no long - term sequelae , and a minority suffer from prolonged dysesthetic pain16,22 ) . but prolonged pain can generate repetitive impulses to the spinal cord and the pain can progress to chronic neuropathic pain . that is an important reason to detect the possible causes of the pain and provide early treatment . the patient described in case 2 , besides the pain , presented with ileus for postoperative 5 days . ileus is often self - limited and usually related to major intraoperative fluid shifts , narcotic use and extensive dissection as well as sympathetic dysfunction . patients most commonly complain that their contralateral extremity is cold as a result of unilateral lumbar sympathetic nerve injury . this sensation is a result of patients feeling warmth in the ipsilateral extremity due to unopposed vasodilation by parasympathetic fibers3 ) . our second patient complained of a cold sensation and dysesthetic pain in the right lower extremity below the knee since she undergoing alif via the left retroperitoneal approach . it is thought that because the surgery resulted in damage to the sympathetic chain of the left side , there was relative sympathetic hyperactivity of the right side . blockade of the sympathetic nervous system is traditionally accomplished at the stellate ganglion or lumbar sympathetic chain , depending on the location of the pain ( upper versus lower extremity)10 ) . sgb is used to treat smp , pain from vascular insufficiency of the upper extremities and orofacial region by decreasing sympathetic activity14,19 ) . lsb is a widely used modality for the evaluation and management of smp in the lower extremities including circulatory insufficiency , a variety of peripheral neuropathy and cancer - related complications24,25,26 ) . the complications of lsb include genitofemoral neuralgia , necrosis of the psoas muscle , injury of the kidney and ureter , bleeding , hypotension and impotence11 ) . however , serious complications related to lsb are rare and the procedure is commonly performed in the outpatient unit . if lsb gives effective results , rf lesioning of the lumbar sympathetic chain can be performed in carefully selected patients15 ) . the precise mechanism that only a small number of patients would suffer from smp although sympathetic chain injuries are common during anterior spine surgery remains unclear . in fact , it is not completely understood why certain individuals develop smp in many neuropathic conditions including post - herpetic neuralgia , trigeminal neuralgia , diabetic neuropathy and cancer pain . it has been postulated that it occurs due to neuronal ischemic changes or an autoimmune phenomenon involving - adrenergic receptors6 ) . in our patients , pre - existing increased sympathetic tone before anterior spinal surgery is also considered to lead to manifest dysesthetic pain . in clinical practice , increased sympathetic tone is often observed in patients with chronic spinal pain . there is a complex relationship between the somatosensory and sympathetic nervous systems , and chronic pain has been well established to induce changes in the sympathetic nervous system6 ) . besides that , the origin of the sympathetic chain is the thoracolumbar ( t1-l3 ) spinal cord , in contrast to the craniosacral distribution of the parasympathetic nervous system17 ) . therefore , the lumbar spinal stenosis , which usually exist below l2/3 , compress cauda fibers containing parasympathetic fibers while sympathetic fibers already left the spinal canal above the level of stenosis9 ) . for the first patient , it is thought that the sympathetic tone of the right side was already elevated before surgery , and acdf through a left anterior approach caused the injury to the sympathetic chain of the left side , leaving behind the increased sympathetic tone of the right side . similarly , for the second patient , it is postulated that spondylolisthesis and lumbar spinal stenosis induced increased the bilateral sympathetic tone before surgery although the symptom was especially severe on the left , and alif with a left approach resulted in the injury to the sympathetic chain of the left side only . early postoperative pain should not be dismissed or overlooked , and it is important to seek possible causes and provide proper interventional pain management . when patients present with early postoperative pain of a neuropathic nature and other possible causes have been ruled out , sympathetic dysfunction should be considered in the differential diagnosis of the severe dysesthetic pain . a sympathetic block , the stellate ganglion for the upper extremities and the lumbar sympathetic chain for the lower extremities , is an effective method for relieving pain due to sympathetic dysfunction .
sympathetic dysfunction is one of the possible complications of anterior spine surgery ; however , it has been underestimated as a cause of complications . we report two successful experiences of treating severe dysesthetic pain occurring after anterior spine surgery , by performing a sympathetic block . the first patient experienced a burning and stabbing pain in the contralateral upper extremity of approach side used in anterior cervical discectomy and fusion , and underwent a stellate ganglion block with a significant relief of his pain . the second patient complained of a cold sensation and severe unexpected pain in the lower extremity of the contralateral side after anterior lumbar interbody fusion and was treated with lumbar sympathetic block . we aimed to describe sympathetically maintained pain as one of the important causes of early postoperative pain and the treatment option chosen for these cases in detail .
Ke$ha In Rehab For Eating Disorder Ke$ha -- In Rehab For Eating Disorder EXCLUSIVE has gone to rehab for an eating disorder ... TMZ has learned.Sources connected to the singer tell TMZ ... she's at Timberline Knolls near Chicago, the same placewent for her issues.We're told the singer -- who's a vegetarian -- was admitted early this morning.Ke$ha tells TMZ, "I'm a crusader for being yourself and loving yourself, but I've found it hard to practice. I'll be unavailable for the next 30 days, seeking treatment for my eating disorder ... to learn to love myself again, exactly as I am."In Ke$ha's recent music video with-- for the song" -- she looks discernibly thinner. ||||| Pop star Ke$ha has entered a rehab facility to help treat an eating disorder, new reports claim. The 26-year-old “Timber” singer checked in to Timberline Knolls in Lemont, Ill., on Friday — the sametreatment center where Demi Lovato did a stint in 2010 to deal with her eating disorder and emotional issues. PHOTOS: Ke$ha Reveals Her Wildest Look Ever Ke$ha admits she’s in rehab, telling media outlets, “I’m a crusader for being yourself and loving yourself, but I’ve found it hard to practice. I’ll be unavailable for the next 30 days, seeking treatment for my eating disorder … to learn to love myself again, exactly as I am.” A vegetarian, Ke$ha is also an ordained minister who got her license online and has performed legal commitment ceremonies for homosexual couples.
– Ke$ha has checked into a 30-day rehab clinic for an unspecified eating disorder, reports TMZ. The 26-year-old singer didn't divulge much in a statement: "I'm a crusader for being yourself and loving yourself, but I've found it hard to practice. I'll be unavailable for the next 30 days, seeking treatment for my eating disorder ... to learn to love myself again, exactly as I am." The vegetarian is in the same Illinois clinic (Timberline Knolls) that treated Disney star Demi Lovato for her eating disorder in 2010, notes Radar.
Australian prime minister says he is ‘deeply shocked and appalled’ by footage of teenager being hooded in a restraint chair and other apparent abuses Australia’s prime minister has launched a public inquiry following the broadcast of footage of children in detention being abused, hooded and bound in a manner likened to Abu Ghraib and Guantánamo Bay. Malcolm Turnbull announced a royal commission hours after the national broadcaster aired shocking footage showing children in detention at the Don Dale facility outside Darwin in the Northern Territory. Footage aired on the ABC’s Four Corners program on Monday showed one youth being stripped and physically held down by guards. In another scene that the program compared with images from Guantánamo Bay or the Abu Ghraib jail in Baghdad, 17-year-old Dylan Voller was shown hooded and tied in a restraint chair for two hours. The chairs are among items recently including in a widened list of “approved restraints” under laws passed by the NT government. Four Corners: I can't see reason, I can only feel anger. And sometimes that's better | Stan Grant Read more Voller – who was featured repeatedly suffering apparent mistreatment at the hands of guards – and five other former Don Dale prisoners intend to sue the Northern Territory government over their treatment in detention. Peter O’Brien, the lawyer representing Voller and another former prisoner, Jake Roper, said Voller was currently in a form of segregated imprisonment in an adult prison and called for his immediate release. “The impact of these years of brutalisation must be immediately measured and he needs immediate assistance.” The footage broadcast on Four Corners was recorded in 2014 and 2015 but the program also looked at long-running issues and instances of mistreatment in the NT’s youth justice system. Turnbull said that he was “deeply shocked ... and appalled” at the instances of abuse at the centre revealed in the investigation. The revelations cast a new spotlight on Australia’s treatment of Indigenous people in general and also on the NT government’s hardline approach to crime. Indigenous youths make up 96% of the young prison population in the Northern Territory and Indigenous people are overwhelmingly represented in the NT prison system across the board. Indigenous people make up 30% of the overall population of the NT. Turnbull said the inquiry would have to examine instances of abuse at the Don Dale facility specifically but it would also consider “whether there is a culture that spreads across the detention system in the Northern Territory, whether it was specific to that centre”. “The important thing is to get to the bottom of what happened at Don Dale and there may be other matters connected to that to be looked into.” He did not call for Don Dale to be immediately shut down but said children in detention should be treated humanely. He said the royal commission would be conducted jointly with the NT government and established as soon as possible. Both Turnbull and the NT chief minister, Adam Giles, emphasised speed, with a commissioner likely to be appointed shortly and substantive evidence to be heard from September. A final report would be tabled early next year. Giles assumed responsibility for the corrections portfolio on Tuesday afternoon after calls for the minister, John Elferink, to resign or be sacked over the revelations of Four Corners. (Elferink remains the state’s attorney general.) In a press conference, he insisted that he had not seen the footage before it was broadcast but watched “with horror”. “I think over time there has most certainly been a culture of cover-up within the corrections system,” Giles said. The police commissioner, Reece Kershaw, also said the footage was new to him. He announced the establishment of a special task force that would investigate whether any criminal offences had been committed. Staff at the Don Dale juvenile detention facility used teargas on youths who were reportedly attempting to escape on 22 August 2014, although CCTV vision showed only one boy had escaped and of the six boys who were exposed to the gas, five were locked in their cells and not all were misbehaving. Northern Territory youth detention: Barnaby Joyce says 'we didn't know' – live Read more Two were shown to be calmly playing cards in their cell moments before the incident. In response to the footage, Unicef Australia raised the possibility that the prolonged periods of solitary confinement, strip searches and use of unjustifiable force of children shown on the Four Corners program “may amount to torture” by the NT government. Many politicians in both government and opposition have expressed shock that such brutal treatment of children could occur in their country. “This is not Australia,” said the deputy prime minister, Barnaby Joyce, who insisted that the Northern Territory senator and Indigenous affairs minister, Nigel Scullion, would have acted if he had known about the abuse. Scullion later said it was “some of the most disturbing footage” he had ever seen and the behaviour of individual officers shown on Four Corners was “evil” and unabashed. “There was no concern about cameras,” he said. “They knew that their behaviour was not right, it was evil, but they also knew they had absolutely no chance of that being a problem to anyone, such was the culture of cover-up.” Tanya Plibersek, the acting leader of Australia’s Labor party, the federal opposition, said she found Four Corners’ report “shocking”. “I think any Australian – any human being, anywhere would have been shocked by the footage. ... It is impossible to think that this has been happening in the Northern Territory for a number of years.” She said Labor supported the royal commission and expected to be involved in setting its terms with the government. “It is absolutely vital that we get to the bottom of what was happening in this detention facility.” But many advocates working in the sector in the NT have expressed a disturbing lack of surprise over the revelations of Four Corners report. Dr Stephen Gray, an associate of Monash University’s Castan Centre for Human Rights Law, says the revelations over the past 24 hours are an unsurprising outcome of the NT’s “strong law and order agenda and its culture of incarceration”. “The detention centre images will damage Australia’s international standing, not to mention the Northern Territory’s position as a place that has supposedly emerged from the old cowboy culture.” Young Indigenous imprisonment in NT: 'You wouldn’t believe it in a modern-day society' Read more The national children’s commissioner, Megan Mitchell, said conditions at the Don Dale centre in particular were “extremely poor” and described her lasting impression as “one of cage wire and cement”. “The MO of the NT government is this: shoot the messenger, discredit the report and demonise these kids, so people out of the street think it’s OK for that to happen to these kids.” Gillian Triggs, the president of the Australian Human Rights Commission, told reporters in Sydney comparisons of the abuses of Don Dale with those in Iraq’s Abu Ghraib were “not too extreme”. She said the abuses at Don Dale were one manifestation of a “trend in Australia over the last 10 years” of detention under extraordinary conditions – often arbitrary, indefinite and without right to appeal. “I would make the broader point that when you chip away at the rule of law and basic rights, ultimately you falter profoundly... with [the emergence of] a culture that has allowed this to occur in the Northern Territory.” Mick Gooda, the social justice and Aboriginal and Torres Strait Islander commissioner, was emotional when he addressed media. “Our people have known about things like this ... and to just see it laid bare in front of us last night must be a wake-up call to everyone in Australia – that something’s got to be done about the way we lock our people up in this country, and particularly the way we lock our kids up. “What we saw last night is an absolute disgrace.” Gooda said Australia needed to examine the underlying causes of why children were being detained in the first place. “I refuse to believe our kids are the most criminal kids in the world, just as I refuse to believe our people are the most criminal.” ||||| Four Corners: Dylan Voller strapped to chair multiple times, former Don Dale guard claims Updated One of the guards involved in the tear-gassing incident at the Don Dale Youth Detention Centre has told Four Corners Dylan Voller had been put in a mechanical restraint chair on at least three occasions before the 2015 vision was filmed. Key points: Footage of Dylan Voller restrained in chair causes shockwaves Chair was used to restrain teen multiple times, Voller and former guard say Accounts contradict NT Government, who said restraint only used on youth once Voller has also told his lawyers he had been in the mechanical restraint chair several times, the first time in youth detention when he was as young as 11. The video obtained by Four Corners of Voller hooded and strapped to a mechanical restraint chair has sent shockwaves around the world. It was broadcast as part of an investigation detailing the repeated assault and mistreatment of children in youth detention, culminating in the tear-gassing of six children in Darwin in 2014. In a written response to Four Corners a Northern Territory Corrections Department spokesman said the restraint chair had been used on youth detainees "once" and that it was used "only at adult correctional centres". Now former youth detention guard Ben Kelleher has come forward to speak out for the first time. Mr Kelleher was a youth justice officer at Don Dale. He has told Four Corners he personally saw Voller in the restraint chair in the Old Don Dale Youth Detention Centre some time before the tear-gassing incident of 2014. "I know of three times he was in the restraint chair," Mr Kelleher said. "Dylan was never so still, he was never so sheepish as he was when he was in that chair. I think he had admitted defeat when it happened. "I turned up for one shift and Dylan was in the chair and the other two times they were on incident reports I read once I got to work," he said. Mr Kelleher worked in youth detention centres in both Darwin and Alice Springs between 2011 and 2014 and worked primarily with the highest risk kids being kept in isolation. As a difficult-to-manage detainee, Voller was well known to Mr Kelleher. Mr Kelleher said at the time he first saw Voller in the chair he did not think it was wrong, but after seeing the vision of the time Voller was strapped to the chair in 2015 he feels uncomfortable. "Now I'm a father, I feel there should be no time a kid should be restrained that way, but at the time I felt that was the way he had been dealt with and I didn't feel qualified to argue the point," he said. "I truly believe no matter how misbehaved a young man or lady is, they shouldn't have their right to movement taken away like that. "The old me two years ago wouldn't have been able to say that because I didn't understand that no one deserves their right to movement or vision be taken away. "It's very hard for the individual and a worker to draw a line between your safety and the safety of the kids." Government should be sacked, lawyer says Voller has told his lawyers he was hooded and strapped in the chair in both the Alice Springs Youth Detention Centre and in the old Don Dale from the age of about 11 or 12. Disturbingly both incidents occurred well before the Northern Territory Parliament moved to amend the Youth Justice Act in 2016 to ensure "that modern mechanical devices of restraint" could be legally used on children. Voller told lawyer Peter O'Brien he was placed the chair after kicking and damaging his cell. "He said he has been in the chair more than one time, he certainly has told us that he's been in several times in the chair, as you've already seen depicted on the program," Mr O'Brien said. "The most concerning thing about that chair is that when it was brought to the attention of corrections, this Government decided to legislate to allow it, to lawfully condone the use of this chair. "That's the sort of people you are dealing with. "They should be sacked, they are dishonest, they have been caught out telling complete untruths and they ought to be gone." 'We did the best we could with what we had' Mr Kelleher said serious shortcomings in staff training and a lack of resources contributed to problems at the centre. "You can see why workers get fed up when there's no clear pathway to fixing the problem. It's shift after shift, and incident after incident. There's no support system," he said. "There's a one day training course and everything else is off the cuff. "You can walk in off the street, apply for a job and the next day you've got a kid's wellbeing in your hands and that is not good enough." He said while working in the Behavioural Management Unit he developed a close relationship with Voller and tried to find constructive ways to manage his behaviour. "The thing about Dylan is that he just wants somebody to give a shit. He's a kid who was forgotten about at home, so you can understand why he wants somebody to hang out with. "The boys you see and the boys portrayed on the tele as being delinquents who deserve a chance, that's absolutely what they are, they deserve a chance." Mr Kelleher said. Mr Kelleher quit working at Don Dale in 2014 after he was investigated for throwing wet toilet paper to conceal a CCTV camera in Voller's cell days before the tear-gassing incident. Topics: law-crime-and-justice, youth, nt First posted ||||| FILE - In this July 10, 2016, file photo, Australian Prime Minister Malcolm Turnbull speaks at the government offices in Sydney. Turnbull has called for an investigation into allegations that teenagers... (Associated Press) FILE - In this July 10, 2016, file photo, Australian Prime Minister Malcolm Turnbull speaks at the government offices in Sydney. Turnbull has called for an investigation into allegations that teenagers... (Associated Press) SYDNEY (AP) — Australia's prime minister ordered a sweeping investigation Tuesday into alleged abuse at a juvenile detention center after video emerged of Aboriginal teens being tear-gassed, stripped naked and shackled to a chair. Prime Minister Malcolm Turnbull said he would launch a Royal Commission — Australia's highest form of inquiry — and suggested that there had been an institutional cover-up of the scandal. Rights groups, however, scoffed at the cover-up claim, saying officials had ignored evidence of abuse in the corrections system for years. The footage, which aired Monday on the Australian Broadcasting Corp.'s investigative program "Four Corners," was filmed largely at a youth detention center in the Northern Territory city of Darwin between 2010 and 2015. Its release triggered a national uproar, with officials from the local level all the way up to the prime minister denying they had ever previously seen it. "We are determined to get to the bottom of this, we're determined to examine the extent to which there has been a culture of abuse and, indeed, whether there has been a culture of a cover-up," Turnbull told reporters. "Why was this abuse, this mistreatment, unrevealed for so long?" When the tear gas incident occurred in 2014, officials said guards used the chemical to subdue six teens who had staged a riot. But closed circuit television and video footage filmed by staff at the center appears to show that the tear gas was used after just one teen escaped his cell, while the other five remained locked in their cells. The guards are heard laughing as the teens cough and cry after multiple shots of tear gas were fired into the isolation wing where they were housed. One of the detainees can be heard saying he can't breathe. In another video, a guard is seen picking up a 13-year-old and hurling him across the room onto his bed. The same boy is also seen in footage from a different Northern Territory detention facility being stripped naked and held face-down on his bed by three guards after he apparently threatened to hurt himself. In yet another instance, the teen was shackled to a restraint chair with a hood placed over his head, before being left alone for hours. Human rights activists accused the government of ignoring the issue until it became public because the teens involved were indigenous. The Northern Territory has the highest rate of youth detention in the country, and 97 percent of its juvenile detainees are Aboriginal. "Amnesty International has repeatedly raised concerns of abuse of children being held in youth detention centers in the Northern Territory," Julian Cleary, Indigenous Rights Campaigner at Amnesty International Australia, said in a statement. "As this program shows, these are not isolated incidents." Indigenous Affairs Minister Nigel Scullion said the footage was particularly shocking because the guards involved appeared cavalier about their actions. He said the officers should face criminal charges. "They knew ... that their behavior was clearly not right, it was evil, but they also knew they had absolutely no chance of that being a problem to anyone," Scullion told reporters in Canberra, the capital. "Such was the culture of cover-up, such was the culture of brutality." The Don Dale Youth Detention Centre has been the subject of complaints for years. Last year, a review of the facility by the Northern Territory Children's Commissioner found an excessive use of solitary confinement and inappropriate use of restraints. Northern Territory Chief Minister Adam Giles said he had never seen the footage before it aired on Monday, also blaming a cover-up within the corrections system for the government's previous inaction. He said he had removed Northern Territory Corrections Minister John Elferink from his position on Tuesday. "I sat and watched the footage and recognized horror through my eyes," Giles told reporters in Darwin. But Priscilla Collins, CEO of the North Australian Aboriginal Justice Agency in Darwin, said officials knew about the footage for years. "There is no cover-up. They've been fully aware of what's been going on," Collins told reporters. "The reports show it, the children's commissioner's report shows it. They had access to the footage." Australia has a checkered history when it comes to its treatment of child detainees. Human rights groups have long criticized the country for its indefinite detention of asylum seekers and their children in remote, offshore immigration detention camps; the government's own human rights watchdog last year found that the policy violates international laws. The United Nations Convention on the Rights of the Child, to which Australia is a party, states that the detention of children should only be a measure of last resort. The Royal Commission is expected to begin holding hearings in September, with a final report due to be released early next year, Turnbull said.
– The Australian government is investigating its youth justice system after footage made public Monday showed teens being mistreated in ways that brought to mind the abuse at Abu Ghraib and Guantanamo Bay, the Guardian reports. The footage from Don Dale Youth Detention Centre shows a 17-year-old tied to a mechanical restraint chair for two hours with a hood over his head. According to ABC, the chair was used on the boy when he was as young as 11. The footage also shows a 13-year-old being stripped naked and held down on his bed in one incident and thrown across a room in another, the AP reports. Back in 2014, officials said they used tear gas on six youths who were rioting. The footage shows only one of those teens was even out of his cell; two were calmly playing cards when they were gassed. Guards could be heard laughing as the teens choked. Australian prime minister Malcolm Turnbull tells the Guardian he was "deeply shocked...and appalled" by the footage. “The important thing is to get to the bottom of what happened at Don Dale and there may be other matters connected to that to be looked into, ” Turnbull says. Those other matters include the fact that 96% of young detainees in the Northern Territory, where Don Dale is located, are Indigenous youths. Officials are blaming a "culture of cover-up" within the justice system, but rights groups aren't buying it, arguing instead that the problem has been ignored by officials for years because the victims are Indigenous people. Six former Don Dale detainees are now suing.
studies of deep - inelastic lepton - nucleon scattering ( dis ) have played a fundamental role in establishing qcd as the strong interaction theory and in exploring the parton structure of the nucleon . with the advent of hera , in which electrons or positrons of 27.5 gev energy collide with protons of 820 gev ( in the last years 920 gev ) , the tests of qcd have been extended by several orders of magnitude with respect to the range in bjorken-@xmath4 and in @xmath5 , the squared momentum transfer between lepton and nucleon . the early fixed target experiments observed scaling violations , i.e. the variation of the structure functions with @xmath5 . the scaling violations are well described by qcd , in which they are related to the gluon density in the proton , and to the strong interaction coupling constant , @xmath1 . at hera the low @xmath4 region was experimentally explored for the first time , and the first measurements@xcite of the proton structure function @xmath6 revealed a steep rise of @xmath2 towards low @xmath4 values . indicating a high gluon density in the proton at low @xmath4 . a key question is then the validity of the dglap evolution equations@xcite at low @xmath4 values , since in the dglap evolution higher order terms proportional to @xmath7 are neglected . one expects that at some value of @xmath4 non - linear gluon interaction effects will become important , damping the rise of the cross section in accordance with unitarity requirements . while this question can not yet be answered , the low @xmath4 region remains a key area for future qcd studies at hera . figure 1 : diagram for lowest order @xmath0 dis at the same time as precision measurements of the inclusive dis cross section and the proton structure functions are being pursued , qcd tests of processes of higher order in @xmath1 are also being investigated . these tests involve the study of jet production in dis , a field for which hera is well suited with its large @xmath0 cms energy @xmath8 gev . this experimental work is intimately connected with theory development , since tests of higher order jet production need the corresponding processes to be quantitatively estimated . inclusive @xmath0 neutral current ( nc ) dis is to lowest order , @xmath9 , described by the diagram in fig . 1 , in which a virtual boson is emitted by the electron and scatters off a parton in the proton . in the one - photon exchange approximation , the double differential cross section can be written as @xmath10 the inelasticity @xmath11 represents the energy fraction transferred to the proton in the scattering process . @xmath2 and @xmath3 are the ( unpolarized , electromagnetic ) proton structure functions and contain the information about the momentum distribution of partons in the proton . they are not calculable in theory and have to be measured . however , when measured at a given @xmath5 value , their evolution in @xmath5 can be predicted in theory . the nc dis cross section can also be written as @xmath12 where the @xmath0 scattering process is considered as the interaction of a flux of virtual photons with the proton . here @xmath13 is the flux factor and @xmath14 defines the photon polarization . @xmath15 and @xmath16 are the cross sections of the interaction of transverse and longitudinally polarized photons with the proton . these cross sections are related to the structure functions : @xmath17 and @xmath18 due to cross section positivity , the relation @xmath19 is obeyed . in the qpm world , without gluons , @xmath20 , since longitudinally polarized photons do not interact with massless spin 1/2 partons . thus , in qpm also @xmath21@xcite . in qcd quarks radiate gluons and interact through gluon exchange . radiated gluons in turn can split into quark - antiquark pairs ( `` sea quarks '' ) or gluons . the gluon radiation results in a transverse momentum component of the quarks , which can now also couple to longitudinally polarized photons . thus , @xmath16 and @xmath3 get non - zero values . due to its origin , @xmath3 is directly dependent on the gluon distribution in the proton and therefore the measurement of @xmath3 provides a sensitive test of qcd at low @xmath4 values . in fact , the low @xmath4 region can not be understood without measuring @xmath3 precisely . figure 2 : @xmath2 vs @xmath5 , for fixed values of @xmath4 . data from zeus and fixed target experiments . the curves show the nlo qcd fit to the data . the @xmath0 cross section is usually written in the `` reduced '' form , in which the @xmath5 dependence due to the photon propagator is removed , @xmath22 since the contribution of the longitudinal structure function @xmath3 to the cross section can be sizeable only at large values of @xmath23 , in a large kinematic range the relation @xmath24 holds to a very good approximation . the h1 and zeus collaborations have recently presented high statistics measurements@xcite of the nc dis cross section and extracted @xmath2 in the kinematic range @xmath25 gev@xmath26 and @xmath27 . the zeus data are shown in fig . 2 . the strong ( positive ) scaling violations at low @xmath4 values , due to the increase of the gluon density ( @xmath28 at low @xmath4 ) , are clearly seen . at large @xmath4 values negative scaling violations appear ( @xmath29 at large @xmath4 ) . the zeus and h1 data are in very good agreement , both with each other and , at the largest @xmath4 values where data overlap , with the earlier fixed target experiments . both collaborations have subjected their @xmath2 data to extensive qcd analyses in next - to - leading - order ( nlo ) , extracting the parton density functions ( pdfs ) and @xmath1@xcite . while the general analysis and fit strategy is similar in both collaborations , there are also many differences in the details , e.g. in the density parametrizations and in the treatment of flavour number and in the use of the fixed target data . an extensive discussion can be found in @xcite . 2 shows that the nlo qcd fits , which are based on the dglap evolution , describe the data very well over no less than four orders of magnitude and down to surprisingly low @xmath5 of a few gev@xmath26 . the gluon density extracted in the nlo qcd fits is shown for both experiments in fig . 3 for three values of @xmath5 . within the error bands there is reasonable agreement . like @xmath2 , the gluon density increases towards low @xmath4 values , and the increase is steeper with increasing @xmath5 . figure 3 : gluon density for three different values of @xmath5 . the error bands show the experimental and ( for h1 ) also the total ( including theoretical ) uncertainty . figure 4 : @xmath1 values obtained in the nlo qcd analyses of @xmath2 data . also shown are @xmath1 values obtained in a recent nnlo analysis@xcite as well as other @xmath1 values obtained at nnlo level . the @xmath1 values obtained in the nlo fits of h1 and zeus are shown in fig . 4 . in the h1 case also the error due only to the experimental uncertainty is shown . thus , the theoretical uncertainty dominates the total error . the major part of this error is due to the choice of renormalization scale , and to a lesser extent , also to the choice of the factorization scale . this is expected to change once next - to - next - to - leading - order ( nnlo ) qcd calculations are available . 4 also shows the result of a recent nnlo analysis of @xmath0 dis data@xcite , in which the moments of @xmath2 are fitted to obtain an impressingly small error on @xmath1 . comparing the @xmath0 dis @xmath1 result with the result obtained when using the more imprecise @xmath30 scattering data , or with the @xmath1 values obtained in nnlo for @xmath31-decays , @xmath32-decays , or in analysis of @xmath33 , it is obvious that the @xmath0 dis data are very competitive in precision determinations of @xmath1 . note that the analysis in @xcite used earlier data on @xmath2@xcite , and not yet the most recent , very precise data . both collaborations are working on further reduction of the experimental errors on the @xmath2 data , errors which are completely dominated by systematics , in particular the uncertainty on the calorimetric energy scale . clearly , theoretical progress is essential in order to profit from future , still better experimental precision in the @xmath2 data . a fully independent measurement of @xmath3 at hera , in a wide range of @xmath4 and @xmath5 , is only possible via a substantial variation of the beam energies ; at any given values of @xmath4 and @xmath5 the difference of the reduced cross section , measured at two values of the cms energy @xmath34 , is a direct measure of @xmath3 : @xmath35 \cdot f_l $ ] . figure 5 : reduced cross section vs. @xmath4 , for @xmath36 gev@xmath26 . the curves are due to the h1 nlo qcd fit and represent @xmath2 and the cross section . this measurement is not yet performed but is part of the hera ii physics program@xcite . while waiting for this to happen , the h1 collaboration has performed several indirect extractions of @xmath3 . the methods of extraction are based on the direct measurement of the cross section in the high @xmath23 region , and on the extrapolation of the precise knowledge of @xmath2 at low values of @xmath23 , into the region of high @xmath23 . cross section measurements of the nc dis process in the high @xmath23 region pose a challenge to the hera experiments , since low energy ( down to 3 gev is achieved ) scattered electrons have to be triggered , identified and well measured . the detailed understanding of the detector and of the photoproduction background is essential and an important part of the measurement is therefore the improvement of both calorimetry and the detection of charged tracks in the h1 central and backward regions . the measurement of track charge and momentum at all scattering angles is particularly important in estimating the amount and shape of the background from photon conversions ( with photons from the @xmath37 decay ) , through the identification of `` wrong '' charge electrons . two methods are used for the extraction of @xmath3 from the cross section measurements , namely the `` subtraction '' method applied at @xmath38 gev@xmath26 , and the `` derivative '' method , applied for @xmath39 gev@xmath26 . the subtraction method is illustrated in fig . 5 , showing the reduced cross section as function of @xmath4 at fixed @xmath36 gev@xmath26 . at the lowest @xmath4 values ( corresponding to high @xmath23 values ) the cross section falls below the @xmath2 curve , extrapolated via the h1 nlo qcd fit . thus , @xmath3 is obtained from the difference @xmath40 . this method was first explored in @xcite and in the recent analyses , using data from 1996 - 97@xcite and 1998 - 2000@xcite , @xmath3 is extracted up to @xmath5 values of 700 gev@xmath26 . 6 shows the @xmath5 dependence of @xmath3 , separately for @xmath41 and @xmath42 data . as it should be , @xmath3 is independent of the lepton beam . one also sees that @xmath3 is clearly different from the extreme possibilities , @xmath43 or @xmath44 . within the precent precision of the data there is good agreement with the qcd expectation , as projected using the h1 nlo fit . in the second method of extracting @xmath3 , the derivative of the reduced cross section with respect to @xmath45 is formed : @xmath46 figure 6 : @xmath3 vs. @xmath5 ( or , equivalently , vs. @xmath4 , upper scale ) , for fixed @xmath47 , for @xmath41 and @xmath42 data . the curves show the h1 nlo qcd fit , obtained for several assumptions on @xmath3 . the shaded band shows the expectation for @xmath3 and its uncertainty from the qcd fit . for @xmath48 the cross section derivative tends to the limit @xmath49 , neglecting the contribution from the derivative of @xmath50 . at largest @xmath23 the @xmath50 contribution dominates the derivative of the reduced cross section @xmath51 . this is in contrast to the influence of @xmath50 on @xmath51 which is dominated by the contribution of @xmath2 for all @xmath23 . a further advantage of the derivative method is that it can be applied down to very low @xmath52 1 gev@xmath26 where a qcd description of @xmath6 is complicated due to higher order and possible non - perturbative corrections . the measured cross section derivative is shown in fig . 7 as a function of @xmath23 , in several bins of @xmath5 . since for a given @xmath5 value , @xmath53 , and since @xmath54 is small for low values of @xmath5 , @xmath55 is linear in @xmath45 to good approximation . this is clearly seen in fig . 7 . in each @xmath5 bin straight line fits were made to the de- rivative data for @xmath56 0.3 . the line fits describe the data very well and the extrapolation of the straight line was taken to represent the contribution of @xmath2 at high @xmath23 . the small contribution of @xmath57 to the derivative was corrected for by using nlo qcd and the correction was included in the overall error of the measured @xmath50 . the derivative method was used in the analysis of the low @xmath5 data , both in the 1996 - 97 data@xcite and in the 1999 - 2000 data@xcite . since the latter data have higher @xmath58 beam energy , 920 gev as compared to 820 gev in the earlier data , the accessible @xmath4 range could be extended to even smaller values . it is also worthwhile to note that the h1 nlo fit is based on the 1996 - 97 data ; when using this fit in the analyses of the later data proper account was taken in order to correct for the difference in @xmath58 beam energy . figure 7 : measurement of @xmath59 vs. @xmath23 , in bins of @xmath5 . the curves represent the nlo qcd fit to the h1 1996/97 data for @xmath56 0.35 and @xmath60 3.5 gev@xmath26 , calculated for several assumptions on @xmath50 . figure 8 : longitudinal structure function @xmath3 vs. @xmath4 and in bins of @xmath5 , obtained by h1 and fixed target experiments . error bands are due to experimental ( inner ) and model ( outer ) uncertainties using the h1 nlo qcd fit to the h1 1996/97 data for @xmath56 0.35 and @xmath60 3.5 gev@xmath26 . fig . 8 gives an overview of the current h1 data on @xmath61 in the @xmath5 range @xmath62 gev@xmath26@xcite . the data extend the knowledge of @xmath3 into the region of low @xmath4 , much beyond the range of the fixed target experiments . the increase of @xmath63 towards low @xmath4 is consistent with the nlo qcd calculation , reflecting the rise of the gluon density in this region . the values of @xmath63 are thus severely constrained by the present data , unless there are deviations from the assumed extrapolation of @xmath2 into the region of large @xmath23 corresponding to the smallest @xmath4 . @xmath3 has also been calculated in the zeus nlo qcd fit@xcite ; the calculation is consistent with the h1 data . figure 9 : diagrams for qcd compton and boson gluon fusion processes . the fully inclusive dis process , shown in fig . 1 , is of zero order in @xmath1 . there is direct sensitivity only to the quark pdf s , and the determination of @xmath1 and gluon density is indirect , via the scaling violations of @xmath2 , measured over a large range of @xmath4 and @xmath5 . the dis processes shown in figs . 9a and b , qcd compton ( qcdc ) scattering and boson gluon fusion ( bgf ) , are of order @xmath1 and due to the latter contribution there is direct sensitivity to the gluon density of the proton . at high enough energy , the involved final state partons manifest as jets of hadrons . the multi - jet final state can be characterized by the jet mass , @xmath64 , and the variable @xmath65 . the dijet mass @xmath64 gives the cm energy of the boson - parton reaction and the fractional momentum @xmath4 ( the longitudinal momentum fraction of the proton carried by the parton specified by the pdfs ) is given by @xmath66 , which is much larger than @xmath67 if @xmath64 is large . two hard scales enter in these diagrams , @xmath5 and @xmath68 . studies of the dynamics of multi - jet production are usually performed in the breit frame , where the virtual boson interacts head - on with the proton@xcite . in lowest order , @xmath9 , the parton from the proton is backscattered into opposite direction , and no transverse energy is produced . thus , appearance of jets with large @xmath69 can only be explained by hard qcd processes of at least @xmath70 , and @xmath68 is then the physical scale at which e.g. hard gluon radiation is resolved . experimentally , jets are usually identified using a @xmath71 algorithm@xcite . the h1 and zeus collaborations have recently presented high statistics studies of inclusive jet and dijet production in nc dis@xcite . the data span the kinematic range @xmath72 gev@xmath26 and @xmath73 gev . nlo qcd calculations in general describe the data very well , over almost the whole range of @xmath5 and @xmath68 . this is exemplified in fig . 10 , showing the h1 inclusive jet cross section as function of @xmath68 and @xmath5 , and in fig . 11 , showing the zeus dijet cross section as function of @xmath5 . the largest uncertainty in the qcd calculations stems from the uncertainty in the choice of renormalization scale @xmath74 , which is taken either as @xmath75 or as mean jet transverse energy , @xmath76 . the uncertainty is largest for low @xmath5 values ( fig . 11b ) , and cuts are made at 150 ( h1 ) and 470 ( zeus ) gev@xmath26 in the qcd analyses of the data . at large values of @xmath5 the experimental uncertainties are also smaller , and this is true as well for the hadronic ( parton - to - hadron ) corrections to the nlo calculations , as shown in figs . 10 and 11c . once the good agreement of the qcd calculation with the jet data has been established , one can proceed to perform a qcd analysis , determining @xmath1 and the gluon density . the analysis strategy is as follows : 1 . fit the jet data to the nlo qcd predictions , using pdfs obtained from global , external fits@xcite . with the pdfs externally fixed , there is only one free parameter , namely @xmath1 . note that the pdfs themselves depend implicitly on @xmath1 , and that this complication was properly taken into account in the fits . 2 . after establishing that the fitted @xmath1 value agrees well with other , external measurements , @xmath1 is fixed ( e.g. to the world average ) and the jet data are then fitted in order to extract the pdfs , in particular the gluon density of the proton . 3 . finally , a global , simultaneous fit of both @xmath1 and the pdfs can be performed . this would be a more independent test of qcd with the data . however , although in this global fit the quark pdfs emerge as identical to those resulting from the fit in step ( 2 ) , the simultaneous fit fails to produce meaningful results for @xmath1 and the gluon density . the reason is + figure 10 : inclusive jet cross section vs. @xmath68 , in several intervals of @xmath5 . also shown are nlo qcd calculations , with and without hadronic corrections . + figure 11 : dijet cross section vs. @xmath5 . the shaded band represents the calorimeter energy scale uncertainty . the curves show nlo qcd calculations for several choices of @xmath74 and proton pdf sets . b ) ratio data / theory showing in addition the effect of the theoretical scale uncertainty . c ) parton - to - hadron correction . + the strong anti - correlation between @xmath1 and the gluon density , which can be understood from the fact that in the phase space region considered , jet production is dominated by the gluon contribution , which enters in the cross section as the product @xmath77 . figure 12 : @xmath1 running in 2 scales , @xmath68 and @xmath75 . uncertainties due to calorimeter energy scale and to theory are indicated in the zeus plot . upper curves show the rge prediction . figure 13 : gluon density in the proton , determined in a combined qcd fit using inclusive dis , inclusive jet and dijet cross sections . the error band includes all experimental and theoretical uncertainties , also that of @xmath78 . both h1 and zeus have performed step 1 in this strategy , and the resulting @xmath1 measurements are shown in fig . note that the `` running '' of @xmath1 is here clearly seen in both scales , @xmath75 and @xmath68 , and the running is moreover seen within each single experiment . the running is consistent with the renormalization group equation ( rge ) . the comparison of the measurements with other hera measurements , and with the world average values is given in fig . the fact that the @xmath1 values obtained from the dis jet data agree very well with other measurements , in particular with measurements from processes which do not involve hadrons in the initial state , like @xmath79 annihilation to hadrons , can be taken as proof of the validity of perturbative qcd at nlo in dis jet production . step 2 in the strategy was performed by h1 , and the gluon density extracted from the data is shown in fig . 13 . the fit includes the combined cross sections of inclusive jet data , dijet data and inclusive dis . the result is in good agreement with recent global analyses@xcite . for a detailed comparison of this result with the gluon densities obtained from the @xmath2 scaling violations , see @xcite . figure 14 : a ) integrated jet shape and b ) mean subjet multiplicity as functions of @xmath68 . nlo qcd calculations are shown for three different values of @xmath1 . at sufficiently high transverse jet energy , @xmath80 , fragmentation effects become negligible and both the shape and other features of the internal jet structure are expected to be calculable in perturbative qcd . the zeus collaboration has recently presented@xcite several results based on studies of jet substructure , using the variables@xcite `` integrated jet shape '' @xmath81 and `` mean subjet multiplicity '' @xmath82 : @xmath83 and @xmath84 the radius @xmath85 is defined in @xmath86 space , where the jet search is performed . the subjets within a given jet are found by repeating the jet algorithm with smaller resolution scale . among the results presented in @xcite are * the average subjet multiplicity in jets in charged current ( cc ) and nc events is found to be similar . since the jets in cc and nc dis are predominatly quark initiated , the similarity in jet substructure indicates that the pattern of parton radiation within a quark jet is independent of the specific hard scattering process . * in a dijet event sample , @xmath87-quark jets were tagged through the identification of a @xmath88 meson . the internal structure of the charm induced jets is found to be similar to that of the quark jets in nc dis . since the latter are dominantly light quark initiated , one can conclude that the evolution of the outgoing partons , which determines the internal structure of the jet , is independent of the hard subprocess from which the outgoing partons originate . * using the internal jet structure of the tagged , charm induced jets in the dijet event sample , and comparing with the internal jet structure of the total dijet sample , it was possible to extract the internal jet structure of gluon jets . the prediction of qcd , that gluon jets are broader , and contain more subjets , is nicely confirmed . figure 15 : summary of @xmath1 measurements at hera ( given at the @xmath89 mass ) , using inclusive dis data and nlo qcd fits , inclusive jets and dijets , and jet shape and subjet multiplicity . also shown are the world average values ( pdg 2000 , s. bethke ) . the internal jet structure is sensitive to @xmath1 beyond leading order . this sensitivity is demonstrated in fig . 14 a and b , where the integrated jet shape ( for @xmath90 ) and mean subjet multiplicity is shown as functions of @xmath68 . note that the jets become narrower , and that the mean subjet multiplicity decreases as @xmath68 increases . the nlo qcd calculation describes both jetshape and mean subjet multiplicity well , but the calculation also varies strongly with different values of @xmath1 . it is thus clear that the jet substructure data can be used to determine @xmath1 . the method is similar to the one used in the qcd analysis of the inclusive and dijet data described above . external sets of pdfs are used , and the implicit dependence on @xmath1 in these sets is properly taken account of in the fitting . the results of the @xmath1 determination using the jet substructure are shown in fig . 15 , together with other @xmath1 measurements from hera . these new measurements agree well with the others , which is proof of the consistency of the nlo qcd calculations also where the internal jet structure is concerned . a general remark about the measurements in fig . 15 can be made : the experimental errors in these measurements are small and comparable to the error on the world averages@xcite . the total errors on the @xmath1 measurements at hera are in fact everywhere dominated by the theoretical uncertainty . as already noted above , this situation is expected to change when nnlo calculations become available . figure 16 : a ) inclusive three - jet cross section vs. @xmath5 . also shown is the ratio of data to theoretical prediction . b ) ratio of inclusive three - jet and dijet cross sections vs. @xmath5 . lo and nlo qcd calculations are also shown . including the effects of variation in the latter of @xmath78 , renormalization scale @xmath74 and proton gluon density . while the inclusive jet and dijet cross sections are directly sensitive to qcd effects of order @xmath70 , the three - jet cross section in dis is already proportional to @xmath91 in leading order in perturbative qcd . this higher sensitivity to @xmath1 and the greater number of degrees of freedom of the three - jet final state allow the qcd predictions to be tested in more detail in three - jet production . the h1 collaboration has recently presented@xcite a study of dis three - jet events , covering the kinematic range @xmath92 gev@xmath26 and three - jet masses @xmath93 gev . the @xmath5 dependence of the cross section is shown in fig . 16a , together with qcd lo and nlo calculations , the latter with and without hadronic corrections . the nlo calculation , which is due to the recently available program nlojet@xcite , describes the data well over the whole kinematic range , as is also seen in the ratio of data to theory . in the latter plot are also shown the theory uncertainty due to variation of the gluon density , the renormalization scale @xmath94 and @xmath1 . as seen , at large @xmath95 gev@xmath26 the @xmath1 variation gives the largest uncertainty . since both dijet and three - jet production is dominated by gluon induced processes , the uncertainty of the gluon density can be minimized by taking the ratio @xmath96 of three - jet and dijet cross sections , at the same values of @xmath4 and @xmath97 . it can be shown , using the qcd calculations , that dijet and three - jet production involves the same gluon fraction , at similar @xmath5 values . furthermore , many experimental and systematic errors cancel in the ratio . as is evident in fig . 16b , @xmath96 , which is directly proportional to @xmath1 , is experimentally measured and theoretically calculated with small uncertainties over the whole @xmath5 range . thus , given better statistics , a very sensitive test of qcd will be possible with the three - jet data , including a precision measurement of @xmath1 . figure 17 : normalized distributions of @xmath98 and angle @xmath99 in the three - jet cms at low @xmath5 and high @xmath5 . solid and dashed curves show nlo and lo qcd calculations , dotted curves show a three - jet phase space model . the topology of the three - jet final state offers a test of qcd through the angular distributions of @xmath100 and @xmath99 , where @xmath100 is the angle between the highest energy jet and the proton beam , and @xmath99 is the angle between the two planes formed by the highest energy jet and the proton beam , and by the three jets , respectively . these angles are shown in fig . 17 , for two @xmath5 ranges . both lo and nlo qcd calculations describe these normalized distributions well , while a phase space model fails the description . the distributions show that the jets tend to be aligned with either the photon or the proton , i.e. the bremsstrahlung nature of the process ( coherence property of qcd ) is confirmed . similar distributions were previously also observed by the zeus collaboration in three - jet photoproduction@xcite . the dis data are well described by nlo qcd and the dglap evolution , over a large range of @xmath5 and bjorken-@xmath4 . this is true for the inclusive dis cross section , with the structure functions @xmath2 and @xmath3 , as well as for the inclusive jet production and the exclusive dijet and three - jet production and for the internal structure of jets . in many areas the data have reached a high experimental precision , and progress in the tests of perturbative qcd depends crucially on further progress in the theory , where the nnlo calculations for the dis processes are awaited . this is particularly true for the precision determination of @xmath1 at hera , using dis data , where the experimental precision is already at level with the error on the world average , and is expected to improve even further . the running of @xmath1 in accordance with the rge is seen within each single experiment , and in both hard scales , @xmath75 and @xmath68 . some areas , like jets at highest @xmath5 and @xmath68 , and the three - jet final state , are still statistically limited . the hera ii running period will bring a huge improvement of statistics in the coming years . however , in the analyses described in this report , the experiments have in many cases so far only used the data taken in 1995 - 97 , which constitute only about 1/3 of the total hera i data . the remaining 2/3 of the hera i data , from the years 1998 - 2000 , is currently being recalibrated and reprocessed , and will soon be available . it is a pleasure to thank the organizers for the warm and joyful atmosphere in a most interesting and remarkably well prepared conference . i also wish to thank my colleagues in h1 and zeus , for providing the data and results presented in this report and for all their help given to me . gribov and l.n . lipatov , sov.j.nucl.phys . * 15 * , ( 1972 ) 438 and 675 ; + l.n . lipatov , yad.fiz * 20 * ( 1974 ) 181 ; + yu.l . dokshitzer , sov . jetp * 46 * ( 1977 ) 641 ; + g. altarelli and g. parisi , nucl.phys . * b126 * ( 1977 ) 298 . l. bauerdick , a. glazov , m. klein , future measurement of the longitudinal proton structure function at hera , proc . workshop on future physics at hera , eds . g. ingelmann , a. de roeck , r. klanner , hamburg , desy ( 1996 ) , p.77 ; hep - ex/9609017 ( 1996 ) .
several topics from the wide field of qcd studies in deep - inelastic @xmath0 scattering at hera are addressed . they include qcd analyses of the inclusive cross section with the determination of @xmath1 and the proton gluon density from the @xmath2 scaling violations , and the determination of the longitudinal structure function @xmath3 . qcd analyses of inclusive jet and dijet data are also presented . finally jet substructure and three - jet production are discussed .
transport of two - dimensional electrons in state - of - the - art modulation - doped semiconductor heterostructures suffers mainly from small angle scattering off charge fluctuations in the donor layer , which is separated from the two - dimensional electron system by a spacer layer @xcite . the amplitude of the disorder is only a few percent of the fermi energy , and the electron mean free path can exceed hundreds of microns @xcite . under these circumstances , transport through nanostructures much smaller than the mean free path is assumed ballistic , i.e. individual electrons follow almost perfectly the paths prescribed by newton s law under the external applied forces and the forces associated with the nanostructure s confinement potential . impurity scattering is thought of as negligible . nevertheless , experiments , which used spatially resolved recordings of the change in conductance induced by a charged tip of a scanning probe microscope , showed that the current density emerging from a quantum point contact was branched as a result of small angle scattering only @xcite . the reported conductance changes in these and further experiments using the same measurement techniques were much smaller than the conductance quantum @xmath0 . at the same time many experiments have been interpreted in terms of purely ballistic effects , e.g. focusing by electrostatic @xcite and magnetic @xcite fields or wall geometries @xcite even in semiconductor materials with shorter mean free paths . it could thus seem that branching has little impact on macroscopic transport quantities and hence is of no relevance for most transport experiments . the first magnetoresistance peaks recorded for two mesoscopic devices fabricated from the same heterostructure . the inset shows the scanning electron microscope picture of the novel magnetic focusing device . @xmath1 is the magnetic field at which the cyclotron radius is commensurate with the wall length of the device . ] branching of a plane wave front propagating in x - direction . ( a ) the electron wave flow intensity approximated by classical ray dynamics is plotted in gray scale as the plane wave propagates along the @xmath2-direction in the disorder landscape shown as a green / white color rendition in the background . the force in @xmath2-direction is ignored ( quasi-2d ) . the wave front remains a vertical line in coordinate space . vertical lines mark the position of the plane wave front at times @xmath3 , @xmath4 , @xmath5,@xmath6 . the bottom panel displays the wave fronts at these times in phase space ( @xmath7,@xmath8 ) . caustics are identified at the turning points ( purple dots ) . ( b ) flow density @xmath9 as a function of @xmath7 at times @xmath10 and @xmath11 ( vertical cross - sections of the flow density plot in a ) . also shown at the bottom are the corresponding wave fronts in phase space . the flow density peaks at the caustics . ] influence of disorder on the flow density @xmath9 ( gray scale rendition ) emitted from a point source . ( a ) gray scale rendition of the flow density @xmath9 in the @xmath12-plane when particles are emitted from a point source with a cosinusoidal angular distribution . they are subjected to the disorder potential color - coded in green and white . forces in both x and y - direction were taken into account and the magnetic field is absent . ( b ) the formation of caustics in a transverse magnetic focusing geometry . particles are emitted from the top point contact . the flow density is plotted on a gray scale at a magnetic field where a caustic forms at the collecting point contact . ( c ) collimation ( left panel ) at @xmath13 and magnetic focusing at @xmath14 ( right panel ) in a corner device consisting of two quantum point contacts placed at a 90@xmath15 angle . red curves in the lower panels show the flow density hitting the lower wall . ( d ) same calculations as in c but in the presence of weak disorder . the standard deviation of the amplitude of the disorder potential corresponds to 2@xmath16 . ] in this article , however , we use a novel magnetic focusing device to demonstrate both experimentally and theoretically that the macroscopic transport quantities of nanostructures can in fact be strongly influenced by branching . this poses the question of how ballistic _ transport effects _ observed in many supposedly ballistic experiments actually are . to illustrate this let us examine the two sections of magnetoresistance curves from two different samples fabricated to the exact same specifications shown in fig . [ fig:0 ] ( details will be given below ) . in an ideal ( i.e. ballistic ) sample patterned in this specific layout ( depicted in the inset ) electrons emitted from point contact c@xmath17 are deflected by a magnetic field and for a certain value @xmath13 will be directed towards the second point contact c@xmath18 . therefore , one expects to observe a single peak in an appropriate transport quantity at @xmath19 . sample 1 shows exactly this behavior , sample 2 , however , shows an unexpected splitting of the peak . so far , many experimentalists would argue that sample 2 is a defective sample , where an unfavorably located impurity spoils the measurement and thus that the sample should be discarded . we show , however , that curve 1 and 2 are both fully compatible with exactly the same amount of impurity scattering and that it can not be argued that sample 1 is in any way better than sample 2 . on the contrary , even though both samples are actually extremely clean devices , it is a rather fortunate coincidence that curve 1 agrees well with the expectations for an ideal system . in addition , our new magnetic focusing device allows us to explain why these consequences of branching have not been seen in previous magnetic focusing geometries . we prelude the detailed presentation of our results by an illustrative explanation of the mechanism of branch formation , as depicted in fig . [ fig:1]a and b. an initially homogeneous particle flow or plane wave front ( restricted source in momentum space ) is propagated along the @xmath2-direction through a two - dimensional disorder potential . a color rendition ( from green to white ) of the disorder potential is plotted in the background of panel a. for the sake of simplicity , only the electrostatic force exerted by the disorder potential in the @xmath7-direction is considered . the force in @xmath2-direction is ignored , so that the longitudinal velocity @xmath20 stays constant and the wave front remains a vertical line in coordinate space . this model makes the principles of branching particularly easy to understand and yet captures all of its important features @xcite . later on , an extension of the model will also allow us to study the statistics of the formation of branches in a magnetic field analytically . the particle or flow density @xmath9 is shown in panel [ fig:1]a using a gray scale . while @xmath9 is initially homogeneous or independent of @xmath7 , it develops features at later times as illustrated in panel b where @xmath21 is plotted at selected times . at a time between @xmath10 and @xmath22 , a strong peak develops in @xmath9 . this heralds the first branch . in the phase space ( @xmath7,@xmath8 ) , the wave front develops a pair of initially coalescing turning points , which subsequently separate ( panel a bottom ) . here , the classical ray density in coordinate space diverges and also the quantum mechanical wave intensity would peak nearby . in between the turning points , the wave front folds in phase space and covers the same spatial coordinate three times . as a result , the local density is enhanced . the path traced by a turning point constitutes a fold line or caustic . a branch is referred to as the spatial region in between two such random caustics . figure [ fig:2]a illustrates another instance of caustic formation and branching when particles are emitted from a point source ( restricted source in coordinate space ) . in this example , no approximation concerning the electrostatic force associated with the disorder potential is made and the full two - dimensional particle dynamics is considered . branches appear on similar length scales as for the simplified plane wave case due to the same basic mechanism . this setup can be implemented straightforwardly in a gaas based 2deg on which a quantum point contact ( qpc ) is patterned either by etching or the split gate technique @xcite . it is instructive to oppose the appearance of branches due to the disorder induced formation of random caustics to the focusing of two - dimensional electrons emitted from a point source in a perpendicular magnetic field @xmath23 in the absence of disorder . we do this , because also in the magnetic focusing problem caustics play an important role @xcite . in a magnetic field , the electrons execute circular cyclotron orbits with a radius @xmath24 , where @xmath25 is the electron density . when emitted from a point source , the electron trajectories converge at a distance of one cyclotron diameter away from the point source and a caustic forms . the enhanced local current density can be detected with the help of a second collecting quantum point contact in the transverse magnetic focusing geometry shown in fig . [ fig:2]b @xcite . the collecting qpc is at a distance @xmath26 from the emitting contact . the enhanced local density due to magnetic focusing arises at a magnetic field for which the cyclotron diameter @xmath27 equals @xmath26 . when enforcing zero net current flow through this qpc and measuring the voltage drop across , the enhanced local density can be detected as a voltage or resistance peak @xcite . one may anticipate that disorder induced branching also produces resistance peaks when sweeping the magnetic field . in order to search for evidence of branching in dc ballistic transport we have chosen the corner shaped device depicted in fig . [ fig:2]c , which , as we will show , can distinguish between deterministic magnetic focusing at the collecting qpc and random focusing caused by branching . the left panel shows trajectories in the absence of disorder at the field @xmath1 for which @xmath28 . the flow density along the bottom boundary is plotted and forms a broad peak centered around the collecting point contact opening for this magnetic field . it is not caused by magnetic focusing since a caustic has not yet developed . rather it results from the collimating properties of the emitting point contact from which electron trajectories leave with a cosinusoidal angular distribution . one may anticipate that it produces a first resistance peak @xcite . at the field @xmath29 ( right panel of figure [ fig:2]c ) , the particle flow converges first into the device corner where a caustic has formed due to magnetic focusing . the corner was chamfered to have well defined reflection . after specular reflection the electron trajectories refocus at the collecting qpc giving rise to another resistance maximum . figures [ fig:2]c and d illustrate how the disorder potential affects the particle flow for both values of the magnetic field . while at @xmath29 the influence of disorder is weak , the flow density has been drastically altered for @xmath13 and now exhibits multiple maxima of comparable size . the magnetic focusing feature at @xmath29 remains largely unaltered and is more robust against disorder induced branching . these conclusions can be generalized and also hold at higher magnetic fields . in the absence of disorder , the flow density reaches a maximum at the collecting qpc for @xmath30 , where @xmath31=1,2,@xmath5 . collimation and focusing are responsible for these maxima at odd and even values of @xmath31 respectively . the collimation features are prone to disorder induced splitting , while the focusing features are generally more resilient . as opposed to the conventional transverse magnetic focusing geometry @xcite , in this corner device deterministic focusing and collimation are separated on the magnetic field axis and hence this geometry lends itself particularly well to confirm the theoretical predictions . the devices are fabricated from a modulation doped gaas / algaas heterostructure in which the 2deg is located 150 nm underneath the crystal surface . split gates , arranged as shown in the insets of fig . [ fig:3 ] , form a 90@xmath15 corner with a qpc along each leg . one split gate is shared by both qpcs and defines the corner . devices with a chamfered corner ( fig . [ fig:3]a and b ) as well as a straight corner ( fig . [ fig:3 ] c ) are investigated . the electron density @xmath25 equals 2.5@xmath32@xmath33 and 2.2@xmath32@xmath33 in the devices used in fig . [ fig:3]a , b , and c respectively . the wall length @xmath26 from each qpc to the corner is 3 @xmath34 m . the electron mean free path of the 2deg is 45 @xmath34 m , one order of magnitude larger than the ballistic electron trajectories relevant for these studies . transport measurements in a perpendicular magnetic field are carried out at 1.4 k by driving a sinusoidal current @xmath35 of 5 na with a frequency of 13.3 hz through the injector qpc . the gate voltage applied to all three gates defining the qpcs is identical . the voltage drop across the detector qpc , @xmath36 , and the injector qpc are detected with separate voltage probes using a lock - in technique ( measurement configuration shown in the insets of fig . [ fig:3 ] ) . three typical experimental data sets are plotted in fig . [ fig:3 ] . the resistance data @xmath37 are recorded on devices which have an identical size but possess different realizations of the disorder . since all devices are fabricated from the same heterostructure , the disorder is characterized by approximately the same statistical parameters . the curves within each panel are acquired for different gate voltage , i.e. different values of the qpc resistances . for the bottom curves at low qpc resistances many modes propagate @xcite . the top curves are recorded for transmission of a single mode . the collimation features at odd values of b / b@xmath38 are in general much broader than the focusing features at even values in agreement with the broad distribution for the particle flow density in the left panel of fig . [ fig:2]c . they frequently split into two peaks depending on the device , i.e. the specific disorder realization ( for instance at @xmath39=1 in panel b and at @xmath39=3 in panel c ) . we assert that the splitting of the collimation features is a result of disorder induced branching as in the left panel of fig . [ fig:2]c . such splitting is absent for the focusing features at even values of @xmath39 . the focusing features are more robust against variations of the disorder potential . the data in panel c were recorded on a device with a corner that is not chamfered . processing as well as depletion will smoothen this corner somewhat however the direction of the specular reflection is not as well defined and focusing features which require specular reflection in this corner have dropped in amplitude . numerical transport simulation and its comparison with experimental results.(a ) the number of trajectories which reach the collecting qpc as a function of @xmath39 in different realizations of the disorder potential in a corner device with chamfered corner . peaks at odd multiples of @xmath1 are strongly affected by branching . the inset shows a contour plot of the potential used to simulate the qpc . ( b - c ) comparison of experimental data ( magnetotransport curves for @xmath40 @xmath41 3 k@xmath42 in figs . [ fig:3]b and [ fig:3]c . ) and numerical simulations for different disorder realizations . ] to corroborate our assertion that the splitting of the collimation features comes from disorder induced branching , we have numerically calculated resistances for different disorder potential realizations . we simulate transport in the corner device by following classical trajectories from the emitting qpc until they either reach the collecting qpc and contribute to the transmission , or until they leave the system to the right of the collector . within the landauer - bttiker - formalism , we approximate the resistance @xmath43 measured in a four - terminal setup to be proportional to the transmission probability from emitter to collector . the qpc is tailored as a sum of variable - depth hyperbolic tangents , and we assume the presence of a saddle potential inside the qpc . soft wall effects due to depletion are modeled by using a quadratic potential @xcite . in the simulations , it is assumed that the particles enter the qpc from a lead with a cosinusoidal angular distribution . the saddle potential then has the effect of collimating the flow . we find that to obtain a collimation peak which is consistent with the experimental results , a saddle potential of approximately 80@xmath44@xmath45 is needed . the precise functional form of the saddle potential is given in [ ] , and is illustrated in the inset of fig . [ fig:4 ] . we note that the results presented here do not depend significantly on the parameters which describe the electrostatic walls . the weak disorder potential used in the simulations is modeled as a gaussian random field with zero mean and standard deviation of the amplitude of the disorder potential v@xmath38 = 2@xmath44e@xmath46 , and a gaussian correlation function @xmath47 = @xmath48 , with correlation length @xmath49 = 180 nm . as these parameters are not readily accessible in the experiment , they were chosen from a realistic range of values @xcite . the mean free path in this model potential is even larger than the measured mean free path , which is limited by other scattering processes , e.g. scattering by charged crystal defects . these are , however only relevant on length scales larger than our system size . although our model system is even `` deeper '' in the ballistic regime than suggested by the experimentally evaluated mean free path , the weak disorder nevertheless has a pronounced effect on the peak structure . figure [ fig:4]a shows calculated resistance traces for different realizations of disorder potential with the same statistical parameters . we point out that the results are not sensitive to small variations in the parameters chosen for the random potential . figures [ fig:4]b and [ fig:4]c compare the experimental traces from figs . [ fig:3]b and [ fig:3]c with the calculated resistances . finding potential disorder landscapes which produce such excellent agreement with experiment is to some extent accidental . quantification of the influence of disorder . ( a ) the average distance an electron travels until a caustic forms as a function of the disorder parameters for @xmath50 , @xmath51 and @xmath52 . the dotted lines mark the parameters of the random potential chosen for the simulations in fig . [ fig:4 ] . ( b ) the numerically calculated inverse participation ratio ( ipr ) of the flow density along the bottom boundary between @xmath2 = 0.5@xmath26 and @xmath2 = 1.5@xmath26 , where @xmath26 is the distance from qpc to the corner , as a function of the standard deviation of the amplitude of the disorder potential under collimation and focusing conditions ( @xmath13 and @xmath14 ) , averaged over 200 realizations of the random potential . the correlation length is identical to the one for the calculations in fig . [ fig:2 ] , and the ipr is normalized by the ipr of the clean system . the rising ipr at @xmath13 indicates that increasing disorder produces more peaks in the flow density , while the focusing peak at @xmath14 is broadened by the disorder . ] the main purpose of the simulations is to demonstrate that different disorder landscapes characterized by the same statistical parameters can indeed either lead to a pronounced splitting of collimation related peaks as one would expect from the behavior of the flow density at the sample boundary in the bottom left panel of fig . [ fig:2]d , or not . the focusing features at even values of @xmath39 do not show any splittings for the chosen parameters of the disorder . with decreasing correlation length or increasing @xmath53 however , we anticipate that also magnetic focusing features are affected by disorder induced branching . to assess the influence of the disorder as a function of the correlation length and @xmath53 , it is instructive to calculate the average distance an electron travels until a caustic forms , @xmath54 . we have obtained an analytical expression for this quantity , which is given by @xmath55^{2}+\textrm{bi}\left[-\kappa^{2}b^{2}\right]^{2}\right)\ ] ] where ai and bi are airy functions of the first and second kind and where @xmath56 is a function of the disorder potential ( see appendix a ) . our result is plotted in fig . [ fig:5]a for @xmath57 , @xmath1 and @xmath29 . for the latter field , magnetic focusing causes a caustic in our corner geometry after electrons have traveled on average a distance @xmath58 . indeed , @xmath54 saturates to this value in the limit of large correlation lengths and small @xmath53 . for both values of the magnetic field we observe that for the parameters chosen in the simulations ( indicated by dashed vertical lines ) the mean distance to the first caustic starts to deviate from the case of magnetic focusing without disorder . for zero magnetic field @xmath54 scales like @xmath59 . @xcite hence , branching can occur on much shorter length scales than the mean free path , which scales as @xmath60 . @xcite our analytical calculation shows that branching influences the transmission properties of our device . from fig . [ fig:5]a it is however not apparent that disorder has a different impact on collimation ( @xmath61 ) than on focusing features ( @xmath62 ) . to assess the impact of branching more quantitatively , we study the peakedness of the flow density along the bottom boundary of the corner device . examples of the flow density @xmath63 are displayed in fig . [ fig:2]c and d. as evident from this figure , the disorder potential induces multiple peaks near the bottom qpc at @xmath61 , while the peakedness of the flow density for @xmath64 resembles that of the flow density in the absence of disorder . to capture the peakedness of the curves in a single quantity we use the inverse participation ratio ipr[i]=@xmath65 . this inverse participation ratio in the vicinity of the bottom qpc is plotted as a function of the standard deviation of the disorder amplitude in fig . [ fig:5]b . for the collimation condition @xmath61 , ipr[i ] rapidly rises to higher values . it reflects the appearance of additional peaks . under focusing conditions , ipr[i ] drops indicating that the original peak mainly broadens . this confirms our experimental observations . in conclusion , the weak disorder potential , which is present in any real two dimensional electron gas , causes a pronounced modification of collimation features due to branching . our findings indicate that branching needs to be taken into account when interpreting transport data of mesoscopic devices even for state - of - the art heterostructures , for which the mean free path is an order of magnitude larger than the device size . dm and jjm contributed equally to this work . we acknowledge technical support of ulrike waizmann and monika riek . this work was supported by the dfg research group 760 and the bmbf . in order to determine the location of caustics , we consider an equation for the curvature of the action function @xmath66 , which is obtained from the hamilton - jacobi - equation ( hje ) . points along a trajectory where the curvature diverges indicate the position of a caustic . in a constant magnetic field @xmath23 , the electron trajectories are circular . considering small deviations from the circular paths in polar coordinates @xmath67 allows a quasi-2d treatment , similar to the one of fig . 2 , in which time is identified with the angular variable as follows . the hje in the symmetric gauge with vector potential @xmath68 is given by @xmath69 where we have identified @xmath70 with @xmath71 . taking two derivatives with respect to @xmath72 , and evaluating the equation for the curvature @xmath73 along the trajectories , we obtain the following equation for @xmath74 : @xmath75 for weak random potentials , we can approximate the correlation function of the random potential as @xmath76 . thus , extending results from refs . [ , , ] , we derive a fokker - planck - equation for the probability density @xmath77 @xmath78 where @xmath79 . for a gaussian correlation function @xmath80 we obtain @xmath81 . to obtain an equation for the onset of the branching , we now derive an expression for the mean time it takes for a caustic to develop along a trajectory . this can be done treating the problem as a mean first passage time problem [ , ] . from this expression , one can then easily derive the mean distance traveled along a trajectory until a caustic is hit . of greatest importance for the experiment is the point source with initial condition @xmath82 . the corresponding mean distance to the first caustic @xmath54 is then calculated [ ] to be @xmath55^{2}+\textrm{bi}\left[-\kappa^{2}b^{2}\right]^{2}\right)\ ] ] where ai and bi are airy functions of the first and second kind [ ] , and where @xmath83 . 33ifxundefined [ 1 ] ifx#1 ifnum [ 1 ] # 1firstoftwo secondoftwo ifx [ 1 ] # 1firstoftwo secondoftwo `` `` # 1''''@noop [ 0]secondoftwosanitize@url [ 0 ] + 12$12 & 12#1212_12%12@startlink[1]@endlink[0]@bib@innerbibempty @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) , @noop ph.d . thesis ( ) @noop * * , ( ) @noop * * , ( ) @noop , , vol . 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we demonstrate that branching of the electron flow in semiconductor nanostructures can strongly affect macroscopic transport quantities and can significantly change their dependence on external parameters compared to the ideal ballistic case even when the system size is much smaller than the mean free path . in a corner - shaped ballistic device based on a gaas / algaas two - dimensional electron gas we observe a splitting of the commensurability peaks in the magnetoresistance curve . we show that a model which includes a random disorder potential of the two - dimensional electron gas can account for the random splitting of the peaks that result from the collimation of the electron beam . the shape of the splitting depends on the particular realization of the disorder potential . at the same time magnetic focusing peaks are largely unaffected by the disorder potential .
An allegation that a white Texas state trooper sexually assaulted a black woman last weekend in Waxahachie went viral on social media. But after the Department of Public Safety published the full body-cam video of the incident, Sherita Dixon-Cole's attorney, Lee Merritt, apologized online and said that the trooper in question had been "falsely accused." Cole, 37, of Grapevine, was pulled over at about 1:30 a.m. Sunday for a traffic violation and arrested on suspicion of driving while intoxicated. She was transported to the Ellis County Jail and charged, according to the DPS. During the stop, Cole alleged, Officer Daniel Hubbard offered her special treatment for sex, then sexually assaulted her, according to a news release tweeted Monday by Merritt. Digital Access For Only $0.99 For the most comprehensive local coverage, subscribe today. The allegations, which the DPS denied Sunday evening, were amplified on social media by Merritt and social activist and journalist Shaun King, who wrote that Cole had been "kidnapped and raped" in posts that were widely shared and re-tweeted from his Facebook and Twitter accounts. He also alleged in an article he wrote for BlackAmericaWeb.com that Hubbard threatened to kill her fiancé if she said anything. A Google search Monday morning for "Shaun King Sherita Cole" returned nearly 150,000 results. King has since deleted his social media posts about the incident. He did not immediately respond to email and text requests for comment. Merritt, a civil rights attorney who left up tweets about Cole's allegations after the video was released, did not immediately respond to a request for a comment or indicate whether he was still representing Cole. The DPS released the full body-cam video, which is nearly two hours long, shortly before midnight on Tuesday and said the department was "appalled that anyone would make such a despicable, slanderous and false accusation against a peace officer who willingly risks his life every day to protect and serve the public." After its release, Merritt apologized. "The body camera footage released directly conflicts with the accounts reported to my office," Merritt wrote on Facebook. "There is no readily apparent evidence of tampering with the footage. Officer Daniel Hubbard seems to comport himself professionally during the duration of the traffic stop and arrest." Merritt wrote that without further evidence, Hubbard "should be cleared of any wrongdoing." "It is deeply troubling when innocent parties are falsely accused and I am truly sorry for any trouble these claims may have caused Officer Hubbard and his family," Merritt wrote. "I take full responsibility for amplifying these claims to the point of national concern." DPS spokesman Lonny Haschel said, "The video shows absolutely no evidence to support the accusations against the trooper during the DWI arrest of the suspect." He said he had no information as to whether Hubbard plans any legal action regarding the allegations made against him. He didn't know whether Merritt had dropped Cole as a client or if she'd taken back her allegations. By Wednesday morning, Cole appeared to have hidden or deleted her Facebook page. Attempts to reach her online and via phone were unsuccessful. SHARE COPY LINK A woman reported being assaulted at a downtown hotel. When police investigated, they discovered the attack started before that. SHARE COPY LINK The Fort Worth Police Department has released a video of a person of interest in the attack on a 13-year-old girl at a school bus stop in west Fort Worth on the morning of April 19. If you recognize this man, call police at 817-392-4222. ||||| Tweet with a location You can add location information to your Tweets, such as your city or precise location, from the web and via third-party applications. You always have the option to delete your Tweet location history. Learn more ||||| "It is deeply troubling when innocent parties are falsely accused and I am truly sorry for any trouble these claims may have caused Officer Hubbard and his family," Merritt said in the statement. "I take full responsibility for amplifying these claims to the point of national concern." Merritt said he thanked the public for echoing the office's demands for justice, but "in this matter it seems your righteous vigilance was abused." King, whose tweet about the allegations was widely shared before it was deleted, could not be reached for comment. His blog post detailing the woman's accusations was taken down Wednesday. He tweeted Wednesday afternoon that the body camera video "did not appear to show any verbal threats, sexual assault, or police brutality." ||||| When the “victim” you fought for turns out to be the victimizer: Sherita Dixon-Cole and the painful consequences of a false report of sexual assault and police misconduct Shaun King Blocked Unblock Follow Following May 23 Sherita Dixon-Cole during a traffic stop On this past Sunday evening, after being contacted by family, friends, and attorneys for a Texas woman named Sherita Dixon-Cole, I was told that she had been sexually assaulted and violently threatened by a police officer while in custody. I was horrified. Sadly, these things happen way too often in our country. I’ve walked victims through this before — many fighting for years on end to prove the truth behind their victimization. Sherita Dixon-Cole’s allegations were genuinely awful. They were also forcefully supported by her fiancé — who was present for some of the encounter they described. Her character and integrity were defended to me by those who knew her well. I probed. Human beings and the decisions they sometimes make are a mystery though. Earlier today I was able to review nearly two hours of body camera footage provided by the police department. The footage appears to be authentic and trustworthy. At no time does it show any of the horrible allegations originally made by Sherita Dixon-Cole. The officer never threatens her or her fiancé as she described. No sexual assault of any kind takes place. From all indications the officer, Daniel Hubbard, was very professional and patient throughout the ordeal. The whole thing was rather routine and painfully normal. The arrest, based on the video, is arguably unwarranted, but that’s rather irrelevant here. The officer administered a field sobriety test and she passed every physical requirement and request over the course of twenty straight minutes of being examined for it. She also passed the breathalyzer test twice — breathing under the legal limit two different times, according to the police report. The officer then communicated to Sherita and her fiancé, who arrived on the scene later, that the arrest was “a courtesy.” That is his prerogative if he still deemed that she was under the influence or was an unsafe driver. That’s how this case should’ve been discussed. That appears to be the most that went wrong here in terms of the actual encounter with the officer. What’s just so baffling is that Sherita was calm and respectful the entire time. Her fiancé was calm and respectful. The officer was calm and respectful. From start to finish Sherita Dixon-Cole was in the custody of the officer for about an hour. It was normal and without incident. Nobody even raised their voices. I’ve watched the whole hour they were together, from start to finish, three different times now. None of the criminal allegations that Sherita Dixon-Cole communicated very clearly to her family, friends, and attorneys ever took place on this video. Not one. Not the threats. Not the sexual assaults. None of it. It is one of the most bizarre things I’ve ever heard of. To this very moment, Sherita Dixon-Cole still insists everything that she said happened…actually happened. She claims the body camera footage must’ve been edited to remove the worst parts. This is not unthinkable. I have seen it happen before, but it absolutely does not appear to happen here. Outside of personal information being blurred out, the video appears to be in its original form. I viewed it with an editing expert. They agree. Nothing horrible took place there. Nothing criminal has been edited out of this video. Furthermore, Sherita Dixon Cole’s behavior and demeanor throughout the video, which is calm, cool, and collected at all times, from start to finish, just does not support her claims of being repeatedly sexually assaulted and threatened. I can’t even begin to make sense of why someone would concoct such an awful story — particularly in light of the reality that both police brutality and sexual assaults are a very real crisis in this nation. It does a tremendous disservice to actual victims when something horrible like this is fabricated. It provides an unfair spotlight to a good cop and undeserved cover for the bad ones who will try to use an incident like this as false proof of their innocence. Sherita Dixon-Cole has no arrest record. She has no known mental health problems. She is an experienced, respected, college educated professional with undergraduate and graduate degrees in human resources. She is known and trusted by people I know and trust. I don’t know why she did this, and I don’t know if we will ever know why, but in this case she played everybody — including it appears — her fiancé and extended family. I learned many years ago that attempting to find a logical explanation for truly illogical behavior is a waste of time. I’ve considered every possible angle here — and every time I end up in the same place — it makes no sense why someone would throw their life away — and damage someone else’s — like she has done. I trusted a very reliable source in this case that I have known for many years. But even in spite of trusting that source, I poked and prodded for holes and was repeatedly assured that Sherita Dixon-Cole has never and would never fake something like this. She proved them all wrong. In most sexual assault cases, all you have is someone’s word and every person connected to Sherita Dixon-Cole believed her words in this case. I regret that I did. Hindsight is 20/20. Every single day I receive hundreds of requests to assist people who’ve been truly victimized in one way or another. I can count on one hand the times I’ve been lied to. It takes a truly emotionally disturbed person to risk ruining their own life to fabricate a crime. Each time it has happened to me, it ripped my heart out, and caused me to genuinely pause to wonder if I could still get out there and fight for victims another day after being lied to. Each time I have — because real people are still being hurt in the worst ways by America’s justice system — and those people deserve and need us fighting tooth and nail for them. Each year in the United States, tens of thousands of people are assaulted, abused, beaten, falsely arrested, and threatened by American police. 2018 is actually on pace to be the deadliest year ever measured for police brutality in this country. But Sherita Dixon-Cole is not one of those victims. She victimized us. She victimized the man she falsely accused and she victimized those who stood up for her — believing that she had experienced the worst crimes. Thankfully, she does not represent anyone but herself. She does not represent actual victims of sex crimes. She does not represent actual victims of police brutality. And she does not represent black women or black people. An awful tendency exists in this country to hold all people of color responsible for the transgressions of one person in that group. That’s racism and it must be rejected here. We reject what Sherita Dixon-Cole has done here. It’s awful. I lead and live with my heart on my sleeve. I don’t know any other way. As I type this, I am working directly with dozens of families across the country who’ve actually experienced police brutality and various miscarriages of justice. I will continue fighting for them like their lives, and all of our lives, depend on it. They deserve that. This woman cannot be allowed to ruin that for other victims. Lastly, from an advocacy perspective, this horrible case only proves that body cameras should indeed be required of all police. They don’t just provide victims the necessary proof of brutality or misconduct, they can also provide police officers the proof of false allegations. We’re nowhere near the point of having the right policies and technology in place on this issue, but we must push forward nonetheless. This stings for all of us. Many good people fought for this person, a complete stranger to us, out of the goodness of our heart. We were right to fight — the system requires us to fight for every ounce of justice we ever get — but someone truly abused us in this circumstance. I’m still so genuinely baffled. ||||| Sherita Dixon-Cole was pulled over early Sunday by a Texas Department of Public Safety officer who suspected her of driving while intoxicated. The story Dixon-Cole spun afterward was alarming: She claimed the trooper repeatedly told her he would let her go in exchange for sexual favors. When she said no, she claimed the trooper sexually assaulted her, according to a statement Monday from her attorney. The 37-year-old North Texas woman’s story was widely shared on social media, aided and amplified by social activist Shaun King, who recently brought attention to the New York lawyer who made xenophobic comments about Spanish-speaking employees at a New York deli. “This system was not designed to protect us — it was designed to punish us,” King wrote in a blog post, “and for it to do anything other than that — we must force it work on our behalf.” But on Tuesday, the Texas Department of Safety released nearly two hours’ of body camera footage that starkly conflicted with Dixon-Cole’s claims. While parts of the video are blurred or inaudible to conceal Dixon-Cole’s personal information, it shows her being pulled over and asked to take a sobriety test. She’s then handcuffed and transported to the Ellis County jail, where she’s charged with a DWI. She was released Sunday night after posting bond. Lee Merritt, Dixon-Cole’s Dallas-based attorney, apologized for her sexual-assault claims in a statement Wednesday, saying the footage conflicted with what was reported to him. “It is deeply troubling when innocent parties are falsely accused, and I am truly sorry for any trouble these claims may have caused [the officer] and his family,” he wrote. “I take full responsibility for amplifying these claims to the point of national concern.” He wrote that his office receives hundreds of abuse complaints from across the country and is obligated to filter them before broadcasting them. His swiftness in publicizing Dixon-Cole’s claims, Merritt wrote, was a means of getting to the truth quickly and accurately. Merritt thanked those who voiced their demands for justice in the wake of the falsified incident. “However,” he wrote, “In this matter it seems your righteous vigilance was abused.” [The curious case of Shaun King, blogger and conservative media target] King, the activist who has worked with a number of anti-police brutality and misconduct causes including Black Lives Matter, appears to have deleted his tweet sharing Dixon-Cole’s allegations. On Wednesday, he tweeted that the body camera footage “does not appear to show any verbal threats, sexual assault, or police brutality.” He also amended his blog post to acknowledge the body camera footage. Still, the incident exemplified the power of King’s position, and the widespread attention to the case could probably be traced back to his sway on Twitter. During the Charlottesville protests in August — when six white supremacists kicked a 20-year-old African American and pummeled him with what appeared to be wooden sticks and a large board — King took it upon himself to try to identify the assailants so they could be arrested. He was credited with identifying at least two of the attackers, The Washington Post’s Ian Shapira reported. On Wednesday afternoon, King — a columnist for national security news site the Intercept — published an article on Medium in part titled “When the ‘victim’ you fought for turns out to be the victimizer,” which addressed Dixon-Cole’s allegations. He wrote that Dixon-Cole stood by her claims and said the body camera footage must have been edited. King disagreed. “This is not unthinkable,” he wrote. “I have seen it happen before, but it absolutely does not appear to happen here. Outside of personal information being blurred out, the video appears to be in its original form.” [Finding the white supremacists who beat a black man in Charlottesville] He went on to write that in the United States, tens of thousands of people are assaulted, abused, falsely arrested and threatened by police. But, he wrote, Dixon-Cole is not one of those victims: She victimized the man she falsely accused and she victimized those who stood up for her — believing that she had experienced the worst crimes. Thankfully, she does not represent anyone but herself. She does not represent actual victims of sex crimes. She does not represent actual victims of police brutality. And she does not represent black women or black people. An awful tendency exists in this country to hold all people of color responsible for the transgressions of one person in that group. That’s racism and it must be rejected here. We reject what Sherita Dixon-Cole has done here. It’s awful. Neither Dixon-Cole nor the trooper could be immediately reached by The Post for comment. The Texas DPS said in a statement that it was authorized by the Ellis County District Attorney’s Office to release the body camera footage after “spurious and false accusations” were brought against the trooper. “The video shows absolutely no evidence to support the egregious and unsubstantiated accusations against the Trooper during the DWI arrest of the suspect,” officials said. “The Department is appalled that anyone would make such a despicable, slanderous and false accusation against a peace officer who willingly risks his life every day to protect and serve the public.” It is not clear whether Dixon-Cole will face criminal charges for her accusations. Ellis County District Attorney’s Office spokeswoman Ann Montgomery said in a statement Thursday that the office is still investigating “exactly what was said, and to whom it was said.” Read more: ‘I didn’t care if they cut my leg off or not’: Kilauea lava bomb survivor describes agony Inside a tractor-trailer pulled over in Texas: Loads of avocados and 88 immigrants ||||| Tweet with a location You can add location information to your Tweets, such as your city or precise location, from the web and via third-party applications. You always have the option to delete your Tweet location history. Learn more
– A civil rights lawyer on Monday claimed there was "significant evidence to substantiate" his client's claim she was raped by a Texas state trooper. Two days later, he said the trooper "should be cleared of any wrongdoing." It was an about-face spurred by the release of a bodycam video from 37-year-old Sherita Dixon-Cole's DWI arrest early Sunday near Dallas, which "appalled" authorities say disproves the "spurious and false accusations," per the Washington Post. Though he'd shared claims that Dixon-Cole was offered special treatment for sex, then raped while "steps were taken to obscure video evidence," Lee Merritt found it impossible to argue with almost two hours of footage, reports the Fort Worth Star-Telegram. It "directly conflicts with the accounts reported to my office" and offers "no readily apparent evidence of tampering," the lawyer now says. Indeed, the camera rolls as Dixon-Cole is pulled over, asked to perform sobriety tests, handcuffed, and taken to jail. "Outside of personal information being blurred out, the video appears to be in its original form," writes journalist Shaun King, who amplified Dixon-Cole's allegations in since-deleted tweets. Though he notes her arrest was "arguably unwarranted" as she passed two Breathalyzer tests, King now says Dixon-Cole's apparently false report was "awful." It's unclear if she'll face charges. On Wednesday, as King revealed Dixon-Cole was sticking to her story, Ellis County's district attorney said his office was still looking into "what was said and who it was said to," per the Dallas Morning News. For his part, Merritt has apologized to the accused trooper and his family, claiming "full responsibility for amplifying these claims to the point of national concern."
Paris (CNN) -- A French writer filed a criminal complaint Tuesday against embattled former IMF chief Dominique Strauss-Kahn, alleging attempted rape, according to her attorney David Koubbi. Tristane Banon, 32, filed the new claim just as a separate New York case against the French financier appeared to be on shaky ground. A Strauss-Kahn lawyer in France said he had filed a counterclaim against Banon for "false declarations." French prosecutors are expected to review the complaint and determine whether there is enough evidence to press charges. Though the alleged attack occurred in 2003, the statute of limitations on attempted rape is 10 years. In an interview with the French news-magazine L'Express, Banon said she decided to act because she was fed up with being labelled a liar, having not previously filed a criminal complaint. Banon said Strauss-Kahn's alleged assault had been widely discussed in light of the charges he faces in New York and she now had a chance to tell her own story and be listened to. "If I want one day to put an end to this hell of the past eight years, it has to go to court," she told the magazine. Asked about the delay in coming forward to report the attempted rape, Banon said it was difficult for all women in this situation. She added that she had been reluctant to go over and over the details, when all she wanted to do was forget about it. It was even harder to face that prospect when the she knew that the attempt would likely fail, she told L'Express, because no-one would believe the word of a young writer over a powerful figure like Strauss-Kahn. Asked if she had concerns about repercussions for bringing the complaint now, Banon told L'Express she feared reprisals because she was a thorn in the side of the former IMF chief On Tuesday, her attorney told CNN that the alleged attack had taken place with "extreme violence." The new legal fireworks came after questions arose about the truthfulness of a housekeeper who alleged that Strauss-Kahn, 62, attacked her in his New York hotel suite in May. Banon said the decision to file the complaint had been taken with her lawyer in mid-June and had not been affected by the sudden crumbling of the case against Strauss-Kahn in New York, according to her interview with L'Express. One of Strauss-Kahn's lawyers in New York, Benjamin Brafman, on Monday declined to comment on the allegations in France. Banon's mother, Socialist politician Anne Mansouret, said shortly after the housekeeper's accusations were splashed across front pages around the world that her daughter had been attacked by Strauss-Kahn in 2003 but that she had discouraged her at the time from filing charges against him. Mansouret, a member of parliament, said she cautioned Banon not to file a police report at the time for fear it would hurt her journalism career. On Tuesday, she said she had not realized before how much her daughter was affected by the alleged incident. "At the time, I never thought that it had traumatized her to such a point," she told CNN affiliate network BFM. Banon "expects to be destroyed" after filing the complaint against Strauss-Kahn, her mother added. But she must "find the combative instinct that is needed to withstand the shock and say to herself, 'OK, I must do this and I will carry it out,'" Mansouret said. Strauss-Kahn was never charged in connection with the alleged attack on Banon. But in light of the charges against Strauss-Kahn after the alleged incident at a Sofitel hotel in New York, Koubbi said a few weeks ago that he and Banon had considered filing a complaint. Koubbi said the cases were not connected. "I don't see any reason why these two cases should be joined, because either the prosecutor has enough elements to condemn Dominique Strauss-Kahn in the United States -- and if he does, he should do it -- or he needs to bring two cases together to get a conviction," he said in June. "In that case, we do not want to participate," he added. Strauss-Kahn's attorney in France, Leon Lef Forster, did not respond to requests for comment on the allegations in May. Mansouret recently pulled out of the Socialist Party presidential primaries. Strauss-Kahn had been a front-runner for the party nomination until the New York arrest, and suggestions that the case was floundering have revived talk of his chances in next year's presidential elections. Mansouret described herself last week as "the woman who embarrasses the Socialist Party." "I am ... a sort of collateral damage in the DSK affair. I knew for a long time that my political career was sealed with this bomb, but I didn't imagine that this bitter past could be revived so violently," she wrote Friday on the Rue89 website, referring to the alleged attack in New York. In May, Mansouret said that in 2003, her journalist daughter had interviewed Strauss-Kahn in his office in the National Assembly. However, after the interview, Banon received a text message from Strauss-Kahn, saying he was not happy with the interview and asking if he could speak with her again, Mansouret said. After Banon arrived at the address Strauss-Kahn had sent her, he locked the door to the room they were in, took her hand and grabbed her arm, according to Mansouret. Banon told him to let her go, and the incident ended with the two struggling on the floor, Mansouret said. Banon managed to escape the apartment and locked herself in her car, where she called her mother. Mansouret said she arrived about an hour and a half later to find her daughter still locked in the car and looking "roughed up." The heel of one shoe was broken, Mansouret recalled. But Mansouret told her daughter not to file a complaint out of concern that she would become known as Strauss-Kahn's victim. CNN does not typically identify sexual assault victims, but Mansouret said her daughter gave permission for her name to be disclosed. In New York, the prosecution's case against Strauss-Kahn has been shaken in recent days after sources revealed that the housekeeper at the Sofitel hotel had been less than truthful with investigators. Within two days after the alleged attack occurred, she spoke by phone with a boyfriend in an Arizona jail in a recorded conversation. A source with knowledge of the investigation told CNN that the housekeeper said "she's fine and this person is rich and there's money to be made," as originally reported by The New York Times. The 32-year-old immigrant has admitted to prosecutors that she lied about her whereabouts following the alleged attack, the details of an asylum application and information she put on tax forms, according to documents filed in court Friday by prosecutors. Prosecutors said Friday that the woman also admitted to lying about being a victim of a gang rape. In angry remarks delivered outside the courthouse, the woman's attorney, Kenneth Thompson, acknowledged problems with his client's credibility. But the bottom line, he said, is that she was attacked. "That was true the day it happened, and it is true today," Thompson said. "She has described that sexual assault many times to the prosecutors and to me. And she has never once changed a single thing about that account." On Tuesday, the attorney for the alleged victim's announced that she had filed a libel lawsuit against the New York Post and five of its reporters, after the newspaper reported that the woman was a prostitute. The woman has accused the newspaper of publishing articles with false and defamatory information in the effort to bolster sales. A spokeswoman for the New York Post, Suzi Halpin, responded to the lawsuit Tuesday, saying "we stand by our reporting." Meanwhile, the indictment and charges against Strauss-Kahn -- including criminal sexual acts and sexual abuse -- still stand. And though he is now free to travel in the United States, a judge said authorities have continued to withhold the French financier's passport. After the charges were filed against him in New York, Strauss-Kahn resigned as director of the International Monetary Fund. CNN's Jim Bittermann, Susan Candiotti, Saskya Vandoorne and Dheepthi Namasivayam contributed to this report. ||||| A television reporter holds a copy of the New York Post outside Manhattan Criminal Court, May 16, 2011. PARIS/NEW YORK (Reuters) - Former IMF chief Dominique Strauss-Kahn was hit with a complaint of attempted rape in France on Tuesday in a new hurdle to any political comeback even as the U.S. sex assault case against him appeared to be falling apart. New York prosecutors were re-examining their case against the potential French presidential candidate after discovering the accuser, a 32-year-old immigrant from Guinea, had lied repeatedly about her background, undermining her credibility as a witness. Strauss-Kahn, 62, had been enjoying his fourth day of release from house arrest in New York when French writer Tristane Banon filed a legal complaint in Paris alleging he had tried to rape her in 2003, when she was 22. Banon, an author and journalist, gave a graphic account in a 2007 TV talk show of her allegation that Strauss-Kahn tried to rape her during an interview in a Paris apartment. Tuesday was the first time she has taken legal action. Her complaint will be examined by a judge who, as a matter of course, would question both Banon and Strauss-Kahn, sending investigators to the United States if necessary, before deciding to either place the Frenchman under investigation or dismiss the case. In New York, charges of sexual assault and attempted rape remained in place against Strauss-Kahn, although he has vehemently denied the allegations and prosecutors acknowledge it would be difficult to make a case against him given the series of lies and contradictions in the accuser's statements. The New York Post cited an unnamed senior investigator as saying prosecutors would drop their charges at a court hearing in two weeks, or even earlier, due to doubts about the credibility of the accuser. "We all know this case is not sustainable," the Post quoted its source as saying on Tuesday. A spokeswoman for the district attorney's office in New York would not confirm that prosecutors plan to drop the charges, saying they were still investigating the case. NEW TWIST In yet another twist to a saga that has captivated much of the world, the accuser sued the New York Post and five of its journalists on Tuesday for reporting she was a prostitute. She filed suit in a court in the Bronx, accusing the Post of publishing false and defamatory articles between July 2-4. The Post reported that the Sofitel housekeeper was a "hooker" who "routinely traded sex for money with male guests" and that after the purported May 14 assault, while under the protection of the District Attorney's office, she "was turning tricks on the taxpayer's dime," the lawsuit said. The Post said, "We stand by our reporting." In Paris, signs that the U.S. charges are unraveling have set off a round of political sparring that threatens to poison the run-up to an April 2012 presidential election that Strauss-Kahn had been tipped to win for the left. French left-wingers, furious that their star candidate has been all but knocked out of the election race, dismissed the Banon complaint as more evidence that Strauss-Kahn's foes were determined to bring him down. "Strauss-Kahn's destiny has been snatched from him. All his friends are asking how it is possible that a man who is director of the IMF and a presidential candidate finds himself in prison a few days before he submits his candidacy," said Socialist deputy Jean-Christophe Cambadelis, a close ally of Strauss-Kahn. "This is clearly a conspiracy against the Socialist Party," he told LCI television. Strauss-Kahn plans to bring a counterclaim against Banon, his lawyer said. The Banon case may fizzle after a preliminary inquiry unless the judge deems there is tangible evidence of an attempted rape. Given the years that have lapsed since the alleged incident, there could be little aside witnesses' conflicting statements to hold up a court case. Unlike the United States, where rules of evidence govern admissibility, the French judge has latitude to look at any facts deemed relevant, including the credibility of the accuser, said Julie Suk, a professor at Benjamin Cardozo School of Law. If the judge believes in his "inner conscience" that a crime took place, the case will go to a trial judge, Suk said. In a U.S. criminal trial, prosecutors must show beyond a reasonable doubt that a crime has been committed. No comparable standard exists in France, Suk said. Regardless of the outcome, opinion polls since the weekend suggest that more than half of French voters think Strauss-Kahn's political career is already over. Strauss-Kahn's abrupt reversals of fortune have angered many French, who viewed his parading before cameras, unshaven and handcuffed in New York as a gross violation of his rights. The "perp walk" -- "perp" being short for perpetrator -- is common in the United States, despite complaints from defense lawyers and civil libertarians. "I've always thought that perp walks were outrageous. We vilify them for the benefit of the theater and circus. They did it in Roman times, too," New York City Mayor Michael Bloomberg told a news conference on Tuesday. Two days after the May 15 "perp walk" Bloomberg had said, "I think it is humiliating, but if you don't want to do the perp walk, don't do the crime." (Additional reporting by Anthony Boadle in Washington and Dominique Bareto in Fort-de-France; Writing by Catherine Bremer and Daniel Trotta; Editing by Louise Ireland and Sandra Maler)
– The Dominique Strauss-Kahn case in New York City may disappear soon, but the DSK headlines keep coming. The maid who accused him of rape is suing the New York Post for reporting that she was a prostitute, notes Reuters. The stories were "an apparent desperate attempt to bolster its rapidly plunging sales," say her lawyers. The Post alleged that the woman worked as a prostitute at the Sofitel Hotel and was continuing to work as a prostitute even while stashed away in a Brooklyn hotel by prosecutors. "All of these statements are false, have subjected the plaintiff to humiliation, scorn, and ridicule throughout the world by falsely portraying her as a prostitute or as a woman who trades her body for money and they constitute defamation and libel per se," says the suit. In France, meanwhile, author Tristane Banon filed her suit against DSK today alleging that he attempted to rape her during an interview, reports CNN. He is suing her for slander in return.
the preparation of thin films of solid ionic conductors helps to improve their application in micro - batteries , fuel cells , and electrochromic devices , see , e.g. @xcite . the resulting large electric fields give rise to nonlinear contributions for the conductivity which in practice turn out to be positive @xcite thus improving the applicability of , e.g. , micro - batteries . from a theoretical perspective the ion dynamics in disordered inorganic ion conductors is a complex multi - particle problem @xcite with strong interactions among the mobile cations @xcite . interestingly , several features of the conductivity have been reproduced by analyzing a single - particle hopping motion in a discrete disordered energy landscape @xcite . recently this approach has found a numerical justification since to a good approximation the ion dynamics can be mapped on a single - particle vacancy dynamics between distinct sites @xcite . also via molecular dynamics simulations key properties of the nonlinear conductivity can be gained for realistic microscopic systems such as alkali silicate systems@xcite . model energy landscapes are frequently used to study transport phenomena such as anomalous diffusion , see , e.g. , @xcite . furthermore , for 1d lattice as well as continuous models it is possible to derive exact expressions for the field - dependent current @xcite . of major current interest is also the study of driven open systems ; see , e.g. , ref.@xcite . interestingly , for periodic boundary conditions the conductivity displays non - analytic behavior at zero field in the thermodynamic limit @xcite . the numerical results indicate that the non - analytic behavior disappears in higher dimensions so that the 1d solution is of no relevance for the experimentally relevant 2d or 3d case @xcite . here to the best of our knowledge no exact solutions exist which describe the field - dependence of the dynamics in a disordered energy landscape . formal solutions have been formulated for general dimensions , which so far could only be evaluated for the 1d case @xcite . for electron hopping transport in disordered semiconductors the population of states can be characterized by a field - dependent effective temperature @xcite . due to the different physical background ( different hopping distances , multi - particle effects ) this solution can not be directly translated into the present problem of interest . a general introduction in the hopping transport in disordered systems can be found in @xcite . without energetic disorder the field - dependence of the current in nearest - neighbor hopping models with point - like sites and the electric field along a coordinate axis reads @xmath0 where @xmath1 is the normalized electric field ( q : charge , @xmath2 : inverse temperature , @xmath3 : hopping distance , @xmath4 : electric field ) @xcite . more generally one expects for isotropic systems @xmath5 an appropriate dimensionless measure for the nonlinearity is given by @xmath6 . for the ordered hopping model , introduced above , @xmath7 is unity if all site - energies are identical , i.e. for @xmath0 . note that @xmath7 can be directly obtained from the experiments and reaches values of the order of 100 @xcite . note that nearest - neighbor hopping dynamics and the presence of discrete sites is by far the dominant transport mechanism in alkali silicate systems in the linear and nonlinear regime @xcite . for single - particle hopping models on a lattice it is has been shown numerically that one obtains @xmath8 for a broad box - type distribution of energies whereas a broad gaussian energy distribution gives rise to @xmath9 , in agreement with the experimental results @xcite . furthermore , for the gaussian case it has been observed that the specific value of @xmath7 is strongly influenced by the presence of some few low - energy sites , representing the low - energy wing of the gaussian . however , beyond these merely numerical results no physical understanding about the underlying mechanisms for the origin of the nonlinear effects has been gained . in this work we discuss a disordered hopping model in arbitrary dimension with a bimodal energy distribution . this model is simple enough that strict analytical results for the nonlinearity can be obtained . however , at the same time it is complex enough that one can clearly extract the non - trivial underlying mechanisms which are responsible for the two different limits of either positive or negative nonlinear behavior . in particular , the numerical results for the box - type and the gaussian distribution , as reported above , can be qualitatively understood based on the results of this work . furthermore , this allows one to suggest the implications of the large positive nonlinear effect , seen experimentally . since in the experiments only the third - order term of the current can be measured with sufficient accuracy we finally express our results in this experimentally relevant limit . more specifically , we will proceed in two steps . ( 1 ) exact numerical calculations are performed for dimensions between 3 and 6 . ( 2 ) an analytical treatment is presented which contains the corrections to the mean - field case ( infinite dimension ) as an expansion in the inverse dimension . it thus becomes a good description in the limit of high dimensions . from comparison of the results of ( 1 ) and ( 2 ) it will turn out that the analytical results already reflect quite well the numerical results for the experimentally relevant 3d case and constitute an excellent reproduction of the results in higher dimensions . the outline of this manuscript is as follows . in sect . ii details of the hopping model and the procedure for the analytical calculations are presented . iii presents the numerical results for the linear and the non - linear conductivity in 3d . next , sect . iv contains the analytical results which are then compared with the numerical results in sect . v. finally , in sect . vi we discuss the results . we consider a @xmath10-dimensional hypercubic lattice where all sites possess an energy , drawn from a bimodal energy distribution . periodic boundary conditions are employed . the two energy values are denoted @xmath11 . their distribution on the lattice is spatially uncorrelated . the fraction of low - energy sites with energy @xmath12 is denoted @xmath13 . this parameter will turn out to be the key parameter for the present analysis . correspondingly , the fraction of high - energy sites is @xmath14 . in total , one has @xmath15 sites . the external field is applied along one of the lattice directions . we introduce the variable @xmath16 via @xmath17 , denoting the number of directions which are orthogonal to the electric field ( e.g. @xmath18 ) . it will serve as an appropriate expansion parameter . as a measure for the disorder we introduce the variable @xmath19 . for any adjacent pair of sites @xmath20 and @xmath21 we define the hopping rate @xmath22 from site @xmath20 to site @xmath21 . specifically , we choose @xmath23 for transitions between equal energies , @xmath24 for the down - rate ( also denoted @xmath25 ) and @xmath26 for the up - rate ( also denoted @xmath27 ) . this choice implies that the barrier between sites with equal energy is larger than the downward barrier from a high - energy to a low - energy site . this is a reasonable assumption for complex energy landscapes @xcite . for reasons of simplicity we choose @xmath28 in our analysis . for hopping processes parallel or anti - parallel to the electric field the jump rates are supplemented by a factor @xmath29 or @xmath30 , respectively . in what follows we use the abbreviation @xmath31 . for finite @xmath32 the stationary population probability @xmath33 in general differs from the boltzmann distribution @xmath34 . from knowledge of the population probabilities the total current can be calculated as @xmath35 where @xmath21 denotes the neighbor site of site @xmath20 parallel to the direction of the field and @xmath36 anti - parallel to this direction . the numerical analysis boils down to the determination of the stationary solution of the corresponding rate equations , i.e. to solving large systems of linear equations . in practice , we have solved the rate equations by the runge - kutta algorithm together with an adaptive step size and determined the stationary long - time limit . the field has been applied along the direction of one axis . for each field strength we have also inverted the electric field so that the resulting current is an uneven function of @xmath32 . we have chosen system sizes @xmath37 , @xmath38 , @xmath39 and @xmath40 , all corresponding to a similar number of total sites . we have checked that upon doubling the system size the values of @xmath7 change less than 3% for @xmath41 and less than 1% for @xmath42 in the relevant limits of small and large @xmath13 ( see below ) . for the disorder we always chose @xmath43 . from the resulting population probabilities the current can be calculated . this procedure is performed for @xmath44 , and @xmath45 . then we fitted @xmath46 to a fifth - order polynomial in @xmath32 and extracted @xmath47 , @xmath48 , and , correspondingly , @xmath7 . we checked that a reduction of @xmath32 by a factor of two did not change the results . thus , the expansion up to the fifth order is sufficient . the final results were averaged over 10 different random realisations of the disorder . and @xmath49 as a function of @xmath13 as obtained from the numerical simulations in 3d . @xmath50 is highlighted by the broken line.,title="fig : " ] and @xmath49 as a function of @xmath13 as obtained from the numerical simulations in 3d . @xmath50 is highlighted by the broken line.,title="fig : " ] we start by showing @xmath51 and @xmath52 for the 3d case ; see fig.[fig1 ] . in the limits @xmath53 and @xmath54 the linear conductivity is identical because the particle is hopping in an energy landscape without any disorder . with the chosen normalization this conductivity equals unity . the conductivity is reduced by two orders of magnitude for intermediate @xmath13 with a minimum around @xmath55 . qualitatively , the decrease of @xmath47 for small @xmath13 is related to the fact that the number of deep - lying traps is increasing which slows down the particle . in contrast , when approaching @xmath56 from below , the residual high - energy states work as barriers , slowing down the dynamics . since the fraction of high - energy states decreases for increasing @xmath13 the conductivity increases correspondingly . the minimum reflects a crossover between the trap - regime and the barrier - regime . also the nonlinear conductivity as expressed via @xmath7 , i.e. the ratio of the nonlinear and the linear conductivity , displays two distinct regimes . since for @xmath57 and @xmath56 one has @xmath58 by construction , we discuss the behavior of @xmath59 in the following . interestingly in the trap - dominated regime one has @xmath60 , i.e. an increase of the nonlinearity as compared to the homogeneous case . in contrast , in the barrier - dominated regime we find @xmath61 so that the nonlinearity is smaller . a physical understanding of these observations will be developed in the remaining part of this work . the simulations for higher dimensions display the same qualitative features . in our analytical calculations we always consider the case of high but finite dimensions , expressed via @xmath62 . we start with the case of a single low - energy state . this low - energy state as well as its direct neighbors are sketched in fig.[fig3 ] . this region will be denoted _ trap_-region . ) local thermodynamic equilibrium is generated , motivating the notion of a trap - region with a border ( circle ) . ] for setting up a set of rate equations we assume that all sites adjacent to the trap - region possess the same non - equilibrium population @xmath63 which , of course , depends on the applied field . later one we argue that this assumption is not required and that it is sufficient in the limit of high dimensions to identify @xmath63 with the average population . then the rate equations read @xmath64 in the stationary case the left side is zero so that one effectively obtains a system of four linear equations . in a first step one can obtain the general equation for @xmath65 and then after insertion solve for the other three populations . whereas the general expression is too complex to directly extract relevant information we restrict ourselves to the limits @xmath66 and @xmath67 . since we always consider the case @xmath62 we express the final result as a linear expansion in @xmath68 . we start by solving this set of equations , i.e. consider a single long - energy site . in the present case we have the two small parameters @xmath68 and @xmath71 . in practice we take the exact solution of this set of linear equations , expand this expression in powers of @xmath72 and then , for fixed order @xmath72 , expand in @xmath68 . finally , one keeps those up to linear order in @xmath68 and @xmath71 . after a straightforward but somewhat lengthy calculation one obtains @xmath73 q_{central } , \label{left } \\ q_{right } & = & \frac{y^{2}}{z^2 } \left [ 1 - \frac{\theta}{z}(y - y^{-1 } ) \right ] q_{central } , \label{right}\end{aligned}\ ] ] with @xmath74 where @xmath75 the factor @xmath76 is close to unity and keeps track of corrections due to finite disorder as expressed by @xmath77 . note that for finite field , i.e. @xmath78 , one obtains @xmath79 . this relation is of key importance for the subsequent discussion . naturally , for vanishing external field , i.e. @xmath80 , the boltzmann populations are recovered . eqs.[ortho]-[right ] have a simple physical interpretation in the limit of large disorder , e.g. when the correction due to the @xmath71-term can be neglected . if a particle is sitting adjacent to a low - energy site the probability to jump to the low - energy site is by a factor of @xmath81 larger than to jump to one of the other @xmath82 neighbor sites . thus , many forward - backward jumps will occur between the low - energy site and its neighbors . as a consequence _ local thermodynamic equilibrium _ is generated around the central site which gives rise to the notation of a trap - region . the @xmath83-factors express that the external field attemps to shift the particle to the right . we mention in passing that this term has been also used in the work of riess and maier @xcite about nonlinear conductivity , but with a very different meaning . the factor of @xmath84 captures the absolute populations in the trap - region as compared to the population of the neighbors . as discussed in appendix a its value ( eq.[cy ] ) can be also rationalized via straightforward flux arguments . the analysis , presented so far , was obtained under the additional assumption that all adjacent sites have the same population @xmath63 . strictly speaking this is not true because the external field induces an anisotropic modification of the population . however , as discussed in appendix b , this assumption can be relieved in the regime of high dimensions and @xmath63 can be simply interpreted as the _ average _ population of the sites adjacent to the tagged region . note that the types of sites , which allow one to obtain this conclusion , only exist for @xmath85 . thus , one might expect that major deviations are present for @xmath86 . it turns out ( see appendix b ) that all higher - order terms in the expansion of @xmath68 ( starting with @xmath87 ) would depend on the individual ( unknown ) populations . exactly in the limit of high dimensions they can be neglected . this justifies that it is reasonable to stop the expansion in @xmath68 after one term . interestingly , already this first term captures many of the features , obtained for the numerical solution in 3d ( see below ) . of particular relevance is the variation of the population of the central site @xmath88 . due to the factor @xmath89 even a small decrease of @xmath90 from unity gives rise to a significant decrease in population of the central site , i.e. particles less likely populate the low - energy site . this population difference has to be redistributed over the whole system , i.e. to the high - energy sites . we note in passing that this phenomenon resembles the poole - frenkel effect , albeit for different physical reasons @xcite . after escaping from the trap - region as a consequence of the external field these particles can now contribute to the total current . since this population increase is induced by the external field , this effect contributes to the nonlinear response of the total system . now we generalize our analysis to a finite fraction @xmath13 of low - energy sites . one can assume that they act independently if the probability that two low - energy sites are neighbors is small . formally , this corresponds to @xmath70 . we choose the normalization such that the average population of a site is just unity , i.e. @xmath91 . in the limit of large @xmath77 a straightforward evaluation of this expression together with eqs.[central]-[right ] yields @xmath92 after an expansion in @xmath68 this can be rewritten as @xmath93 the current ( normalized per site ) , as generated by the sites beyond the trap - region is simply given by @xmath94 . furthermore , one can also calculate the contribution of the trap - regions . although the population may be extremely high in this region it turns out that the current of the trap - region , i.e. @xmath95 is very small due to the factor of @xmath13 and the missing factor of @xmath77 . inserting eq.[qhigh ] in the expression for the current and evaluation of the first - order and third - order terms in @xmath32 yields after a straightforward calculation ( see appendix c ) @xmath96 naturally , for large @xmath16 one recovers the mean - field limit @xmath97 . using the same set of rate equations ( eq.[rate1 ] to eq.[rate4 ] ) as in the previous case one directly performs an expansion in @xmath68 . one obtains after a straightforward calculation @xmath99 q_{rest } , \\ q_{right } & = & [ 1 + \frac{1}{\theta } ( y - 1/y ) ( z-1 ) ] q_{rest}.\end{aligned}\ ] ] note that in contrast to the limit of large disorder the total population in the trap - region is not changed upon application of an external field . in agreement with the previous case @xmath100 is somewhat decreased ( because @xmath101 ) whereas @xmath102 increases . in analogy to the limit of large disorder normalization leads to @xmath103 . for the current , related to one left , one central and one right site one obtains after a short calculation @xmath104(y - 1/y)q_{rest}$ ] . the total current can be written as @xmath105 this can be rewritten as @xmath106(y-1/y).\ ] ] with a calculation in analogy to appendix c one ends up with @xmath107 in contrast to strong disorder the nonlinearity decreases as compared to the homogeneous case . qualitatively , this is due to the fact that upon increasing the external field intensity is shifted from the left to the right site . this shift of population decreases the total current because a particle on the right side is more likely shifted back to the central site and thus contributes with a negative sign . here we deal with the limit that most sites are high - energy states . actually , this limit is already implicitly contained in the previous calculation . the same approximations would have been valid if @xmath109 . if , for the moment , we interpret @xmath13 as the number of high - energy states the value of @xmath7 is again given by eq.[sr1 ] . to keep the original notation we have to substitute @xmath13 by @xmath14 and @xmath77 by @xmath72 in eq.[sr1 ] . this yields @xmath110 thus , independent of the degree of disorder one obtains a reduction of the nonlinearity if most states are low - energy states . the explanation is analogous to before , just the signs have to be reversed . to stress the qualitative picture one may imagine one inaccessible high - energy site . the external field pushes the particles in front of this site . due to the inaccessibility the intensity @xmath100 is increased . since , this left site can not contribute to the current in field direction , there is an effective reduction in the total current . here we introduce a very different approach for the high - dimensional case which is applicable for the whole parameter regime except for the trap - regime and is more general than the solutions , discussed above . the key idea is to use a statistical description which is as close to a mean field description ( infinite @xmath16 ) as possible but still reflects the properties of finite dimensions . generally , two approximations reflect this limit . ( 1 ) after an orthogonal jump the previous site is randomly given a new energy based on the energy distribution , i.e. the memory on the previous site is lost . ( 2 ) for jumps along the field direction more information has to be included because these jumps determine the value of @xmath7 . here the memory is lost after two successive jumps in one direction because then the backjump probability is proportional to @xmath87 . this statistical picture is expected to break down in the case of a trap - regime ( @xmath111 and @xmath69 ) . here after an orthogonal jump from a low - energy to a high - energy site it is essential to know that the previous site was a low - energy site because very likely the system will jump back . within the statistical description , however , the backjump probability would be very small because the energy of the previous site would be determined according to the energy distribution which would , very likely , change the energy and thus suppress the trapping property . the formal description , resulting from ( 1 ) and ( 2 ) requires the introduction of a probability @xmath112 that a particle sits on site @xmath113 and has neighbor sites with energies @xmath36 and @xmath21 anti - parallel and parallel to the field direction , respectively ( @xmath114 ) . then the corresponding master equation reads @xmath115 for the motivation of the individual terms we start by discussing the first term . the rate of jumping from site @xmath36 to site @xmath20 in the direction of the field is proportional to @xmath116 , which is just the probability that two adjacent sites @xmath117 do exist . since we want to calculate the change in the probability @xmath112 we also have to take into account that statistical factor @xmath118 to have an adjacent site @xmath21 . furthermore a factor of @xmath119 keeps track of the direction of the jump . in summary , we obtain a contribution of @xmath120 . to calculate the gain term after an orthogonal transition ( third term ) one has to keep into mind that the rate only depends on the energy difference of the old site ( which was either plus or minus ) and the energy of the new site @xmath20 . furthermore , the product @xmath121 just expresses the probability to find three adjacent sites @xmath122 . as discussed under point ( 1 ) , no memory about the old site ( plus or minus ) is kept . the remaining terms can be derived analogously . for the calculation of the stationary limit this corresponds to a set of 8 coupled linear equations . again we perform a @xmath68 expansion of the resulting population properties and , correspondingly , the resulting current . here we just present the final result which we have checked by solving these equations by maple . in lowest order of @xmath68 the current reads @xmath123 ( y-1/y).\ ] ] this directly yields @xmath124 most importantly , this general relation has eq.[sr1 ] and eq.[sr2 ] as limiting cases if choosing @xmath125 or @xmath126 , respectively . as described above , the trapping picture can not be described by this ansatz . the key results of this work deal with the limits @xmath70 or @xmath127 for the physical relevant limit of high disorder , i.e. @xmath69 . in a first step we compare the numerical results for @xmath41 and @xmath42 for @xmath47 and @xmath7 with the analytical expressions in the respective limits . as before , we use @xmath128 and choose @xmath59 for our comparison . ( left ) and @xmath129 ( right ) for the 3d case . solid lines : analytical solutions for both the limits of small and large @xmath13 . the value of @xmath77 is chosen as @xmath130 . broken line : the analytical solution is scaled by a factor of 1.5.,title="fig : " ] ( left ) and @xmath129 ( right ) for the 3d case . solid lines : analytical solutions for both the limits of small and large @xmath13 . the value of @xmath77 is chosen as @xmath130 . broken line : the analytical solution is scaled by a factor of 1.5.,title="fig : " ] the results for the 3d case are shown in fig.[figc1 ] . the linear conductivity @xmath47 is reproduced very well . qualitatively , @xmath59 is also reproduced for both limits of small @xmath13 and large @xmath13 . interestingly , when scaling the theoretical curve by a constant factor of 1.5 one achieves a perfect agreement between numerics and analytical theory for @xmath131 . this scaling property is just a consequence of the fact that in this regime the individual traps act independently . however , the fact that also the sigmoidal shape of @xmath49 is reproduced clearly shows that the trap - mechanism , as discussed above , fully explains the nature of the nonlinear conductivity in the experimentally relevant 3d case . also the @xmath13-dependence for large @xmath13 , giving rise to negative @xmath59 , is reproduced . however , a quantitative comparison is only possible for @xmath132 . next we compare the numerical and analytical results for @xmath42 ; see fig.[figc2 ] . in agreement with the 3d case the linear conductivity is reproduced very well in both limits . the crossover regime has a similar size ( one order of magnitude on the @xmath13-scale ) but is shifted to somewhat lower @xmath13-values . this is to be expected because the crossover should scale like @xmath68 . most remarkable , the agreement for the non - linearity @xmath59 is very good . the trap - regime is fully reproduced , and the remaining scaling factor is reduced from 1.5 in 3d to 1.08 in 6d . this improvement does not come as a surprise because the analytical theory should be particulary good for high dimensions . a dramatic improvement as compared to the 3d case is observed for the barrier - regime . here a quantitative agreement is seen for @xmath13 as small as 0.3 . obviously , the neglect of back - jump memory is by far more justified for the 6d than for the 3d case . for small @xmath13 ( left ) and large @xmath13 ( right ) . the lines serve as a guide for the eyes . , title="fig : " ] for small @xmath13 ( left ) and large @xmath13 ( right ) . the lines serve as a guide for the eyes . , title="fig : " ] for both dimensions we observe that the breakdown of the theoretical expectation for @xmath47 and @xmath7 in the trap - regime occurs at very similar values of @xmath13 ( 3d : @xmath133 ; 6d : @xmath134 ) . we checked that the same holds if we directly compare @xmath48 with the theoretical expectation . thus , the range of applicability of the linear and nonlinear prediction is very similar . finally , we compare the ratio of the actual numerical and the approximate theoretical value of the nonlinearity parameter @xmath135 ; see fig.[figcall ] . this representation highlights the results , discussed in figs.[figc1 ] and [ figc2 ] and , furthermore , allows one to see the gradual increase of predictability when going beyond the 3d case . in the trap - regime ( small @xmath13 ) we compare the different dimensions as a function of the scaled variable @xmath136 . it turns out that for all dimensions a plateau - value emerges . as discussed above this implies the relevance of the trap - picture for all dimensions . the plateau - value strongly depends on the dimension and approaches one for high dimensions . as discussed before , these deviations reflect that quality of the approximation that @xmath63 can be identified with the average population . it becomes good for high dimensions . interestingly , in all cases the plateau - behavior breaks down for @xmath137 . as mentioned above , the presence of non - adjacent low - energy states and thus the applicability of the analytical approach in the trap - regime was related to the inequality @xmath70 . in the opposite case , i.e. in the barrier - regime , the analytical prediction is good for @xmath138 except for the 3d case where the prediction already fails for @xmath139 . as expected from the range of validity of the underlying approach , the breakdown of this approximation is related to @xmath13 rather than @xmath136 , at least for @xmath140 . we also performed simulations in the limit @xmath141 and @xmath142 , as reflected by eq.[sr1 ] . although the qualitative features , in particular a negative @xmath59 , can be reproduced , a quantitative comparison requires very high dimensions which are beyond the scope of our computer simulations . and @xmath16 as discussed in this work . ] in this work we have described the nonlinearity for a simple lattice model with a bimodal energy distribution in dependence of the fraction of low - energy sites @xmath13 , the disorder ( via @xmath77 ) and the dimension ( via @xmath16 ) . a clear physical picture is presented for the limits of a small number ( @xmath98 ) and a large number ( @xmath143 ) of low - energy states in the limit of large disorder ( @xmath144 ; see fig.[fig_schema ] for a sketch of the whole @xmath145-phase space . in the first case the few low - energy states serve as traps which are in a local thermodynamic equilibrium - state with the adjacent sites . this gives rise to a reshuffling of intensity to the high - energy states so that the positive nonlinear contribution is via the nonlinear increase of the current of the high - energy states , i.e. @xmath146 . in the other limit of many low - energy states the remaining high - energy states serve as barriers which accumulate intensity on the neighbor site opposite to the field direction and decreases the intensity on the adjacent site parallel to the field direction , respectively . the contribution to the total current , however , has the reverse order . thus , one obtains an effective decrease of the non - linear conductivity , i.e. @xmath147 . note that for sufficiently large @xmath77 there exists a regime where @xmath148 does not depend on @xmath13 ( @xmath149 ) . whereas this theoretical plateau value is close to the numerical value for higher dimensions , a difference of a factor of 1.5 is observed for the 3d case ( see fig.[figc1 ] ) . furthermore , in this limit also the @xmath77-dependence is very weak ( only via @xmath150 ) and disappears for large @xmath77 . we mention in passing that also the 2d model displays a plateau value . however , here the numerical value is even two times higher than the theoretical value ( data not shown ) . for large disorder the theoretical predictions are not applicable in the regime @xmath151 ( see fig.[figcall ] ) . note that the critical value @xmath152 for site percolation for high dimensions is approximately @xmath68 ( e.g. @xmath153 @xcite ) . it is known that above the percolation threshold the linear conductivity strongly increases because the particles can cross the sample without using the high - energy states . the present results show that also the nonlinear conductivity shows a significant change around this critical concentration of low - energy sites . however , a closer relation of the crossover - regime to the percolation approach is beyond the scope of this work . from a theoretical perspective one might want to consider more complex energy distributions . although the general physical mechanisms , described in this work , may remain the same , a quantitative analysis would become much more difficult if not intractable within the present approach . e.g. , the analysis of a model with three instead of two different energy levels in the barrier - regime would require the solution of 27 instead of 8 linear equations . nevertheless , the insight of the present work on the two - state model can be used to rationalize the numerical results , previously obtained for hopping models with continuous energy distributions ( see introduction ) . for a gaussian distribution the resulting nonlinearity was analyzed in dependence on the lowest energy @xmath154 of all sites @xcite . among the different realizations of the gaussian random numbers the value of @xmath154 fluctuates quite significantly . it turned out that ( 1 ) only for sufficiently low values of @xmath154 one indeed observes @xmath155 whereas otherwise one has @xmath147 and ( 2 ) in the regime of sufficiently low values of @xmath154 ( i.e. , @xmath156 ) the value of @xmath7 hardly depends on the specific value of @xmath154 @xcite . both observations can be qualitatively explained by the present results . due to the dependence on the single low - energy value @xmath154 the continuous distribution can be related to a discrete model with one particular low - energy state . qualitatively , this corresponds to the present bimodal model in the trap - regime . if @xmath157 is too small one indeed observes @xmath147 because local equilibration does not occur and the nonlinearity is explained via the barrier - mechanism . furthermore , for large @xmath77 no dependence on the disorder is observed ( explanation of observation(2 ) ) . thus , several non - trivial observations from a continuous gaussian distribution can be rationalized by the insights from the bimodal model . in previous simulations also the box - type distribution was analysed somewhat closer . it was shown that in this case one observes @xmath147 @xcite . when mapping this distribution on a bimodal distribution an appropriate choice is @xmath158 . here we obtain @xmath147 in agreement with the numerical result . the rate equations eq.[rate1 ] to eq.[rate4 ] required implementation of the approximation that the population of all neighbor sites is identical . although we found a strict argument why this approximation is not required for the validity of our approach , it is promising that the general approach eq.[formel : mod_mastergl ] yields identical results for the limits @xmath108 as well as @xmath98 together with @xmath67 . this serves as an important consistency check of the two complementary approaches , used in this work . as outlined in the introduction hopping models constitute a reasonable approach for the real - world situation in inorganic ion conductors . the previous numerical results indicated that the experimental observation @xmath146 suggests a very broad distribution of the site energies such that there exist a few sites with very low energies @xcite . however , in the previous work no physical picture for this observation could be supplied . the present work suggests that the presence of these low - energy sites gives rise to the phenomenon of local thermodynamic equilibrium which is responsible for the experimental observation @xmath146 . please note that the terminology of sites was related to the vacancy picture . going back to the ion rather than the vacancy picture the positive nonlinear effect translates into the presence of a few unfavorable sites which nevertheless have to be frequently visited by the ion due to the shortage of vacant sites . in summary , to the best of our knowledge we have for the first time formulated quantitative predictions for the non - linear response of a disordered hopping model in high dimensions with several predictions which semi - quantitatively already hold for the experimentally relevant 3d case and hold very well for even higher dimensions . thus , the experimentally observed positive nonlinear effect indicates the presence of strong disorder with only a few sites with very low energy as outlined for the case of the gaussian distribution . a more direct experimental analysis of non - linear single - particle dynamics is possible with modern holographic - mechanical optical tweezers @xcite which can generate random potentials and may allow for a more quantitative comparison with the dynamics in disordered energy landscapes . we acknowledge very helpful discussions with b. roling , s. rthel , t. franosch , and s. egelhaaf about this project . in particular we would like to acknowledge the very fruitful collaboration with our late colleague r. friedrich on the topic of this work . we gratefully acknowledge the financial support by the dfg via for 1348 and sfb 458 . here we present an alternative argument for eq.[cy ] in the limit @xmath159 . in the stationary non - equilibrium case the total fluxes in and out of the trap - region have to be identical . counting the number of possible transitions the flux balance can be written as @xmath160 neglecting the terms of order @xmath161 and using eqs.[ortho]-[right ] ( without the correction terms of order @xmath71 ) this can be rewritten as @xmath162 which after expansion in @xmath68 and comparison with eq.[ortho ] directly yields eq.[cy ] ( again without the correction terms ) . thus , the factor @xmath84 balances the increase of intensity of @xmath163 , following from @xmath164 for @xmath165 . here we show that for the derivation of the leading term of @xmath166 it does not matter whether the populations of the sites , adjacent to the trap - region , are identical or not . using a vector notation we choose the central site as @xmath167 , the left and right sites as @xmath168 and the orthogonal sites as @xmath169 . coordinates different from zero are explicitly listed .then the neighbors of the trap - region can be classified into six types : ( 1 ) @xmath170 , ( 2 ) @xmath171 , ( 3 ) @xmath172 , ( 4 ) @xmath173 , ( 5 ) @xmath174 , ( 6 ) @xmath175 . within one type all populations are identical due to symmetry reasons . the individual populations are denoted @xmath176 with @xmath177 . the number of sites @xmath178 can be easily calculated . it turns out that only @xmath179 is of order @xmath180 ( namely @xmath181 ) whereas all other @xmath178 are at most of order @xmath16 @xmath182 . the total number of sites @xmath183 is @xmath184 . denoting @xmath63 as the average population of a site one has the simple relation @xmath185 in the mean - field limit @xmath186 one can write @xmath187 because the boltzmann probabilities are recovered . for finite but large dimension one can choose the expansion ansatz @xmath188 where , again , @xmath63 denotes the average population of all sites . inserting this ansatz into eq.[app1 ] and comparing all terms of order @xmath16 one immediately obtains @xmath189 . thus , in case of symmetry breaking the impact of finite order on @xmath190 is only of order @xmath87 . going back to the rate equations eq.[rate1 ] to eq.[rate4 ] one has to modify the source terms by replacing @xmath63 by the specific populations @xmath176 , defined above . after a straightforward calculation one realizes that for the relevant orders in @xmath16 only the term @xmath191 would contribute which , however , is zero . thus , all variations of @xmath176 from @xmath63 are irrelevant for the first order expansion in @xmath68 and would only show up in the higher - order terms . of course , the above arguments can be also applied for the next shell of sites around the sites considered above . again , there is one type of sites which dominates all other sites in the limit of high dimensions . reiterating this argument one can conclude that @xmath63 can be even identified with the average population of all sites of the system beyond the tagged region if one restricts oneself to the corrections of order @xmath68 . we mention in passing that for the 2d case ( @xmath192 ) one has @xmath193 . thus , the key states for argumentation only start to exist for @xmath41 and a quantitative comparison for the 2d case should be quite poor . this is indeed reflected by the actual comparison as indicated in the main text .
nonlinear effects are omnipresent in thin films of ion conducting materials showing up as a significant increase of the conductivity . for a disordered hopping model general physical mechanisms are identified giving rise to the occurrence of positive or negative nonlinear effects , respectively . analytical results are obtained in the limit of high but finite dimensions . they are compared with the numerical results for 3d up to 6d systems . a very good agreement can be found , in particular for higher dimensions . the results can also be used to rationalize previous numerical simulations . the implications for the interpretation of nonlinear conductivity experiments on inorganic ion conductors are discussed .
the limb girdle muscular dystrophies ( lgmd ) are a clinically and genetically heterogeneous group of primary muscle disorders characterised by progressive weakness and wasting , predominating in muscles of the pelvic and shoulder girdle , with occasional involvement of the myocardium . to date , 15 genes for autosomal recessive lgmd ( lgmd2 ) have been identified . because of the broad phenotypic variability both within groups and within families , delineation of genotype - phenotype correlations between these different subtypes is challenging . the accurate diagnosis can only be made by molecular genetic analysis , which is usually guided by protein analysis in a muscle biopsy whenever a decrease of any of the known lgmd2 proteins can be documented . in addition , in the past years muscle magnetic resonance imaging ( mri ) has been applied increasingly to determine distinct patterns of muscle involvement , which may point to a specific genetic subtype . moreover , it has been shown that it can be helpful to consider the geographical and ethnic origin of an affected individual in the differential diagnosis because of the occurrence of founder mutations in some subpopulations . in particular , homozygous mutations can generally be expected to underlie the disease in consanguineous families and in patients whose ancestors originate from the same geographic area . however , the disease causing mutations still remain undetected in a large number of lgmd2 patients . recent molecular genetic studies have shown considerable progress in the identification of recessive disease causing genes using the positional cloning / candidate approach by homozygosity mapping . by definition , homozygosity mapping , also known as autozygosity mapping , tests the assumption that a homozygous mutation in a recessive disease is identical by descent by segregating twice to the affected person from a common ancestor through both the maternal and paternal line . the value of single nucleotide polymorphism ( snp ) array - based homozygosity mapping , i.e. an indirect dna analysis as a first step to the identification of a disease - causing mutation , has recently been evaluated by hildebrandt et al . , who retrospectively studied 72 individuals carrying known homozygous mutations and originating from both inbred and outbred populations . here we show that snp - array - homozygosity mapping used in an affected individual only can guide molecular genetic testing in lgmd2 , if there is known consanguinity of the parents . the present study included a consanguineous turkish family ( here called md1 ) with two sibs affected with lgmd2 , and another austrian patient ( here called md2 ) with sporadic lgmd and known consanguinity of the parents . clinical and electrophysiological studies followed standard methods and were performed with written informed consent and approved by the local ethical committee of the medical university of graz , austria . two healthy unrelated individuals from an outbred population were selected as controls to compare 10 k and 250 k snp array data . part of the muscle biopsy was fixed in formaldehyde and embedded in paraffin and the rest was rapidly frozen in isopentane cooled in liquid nitrogen . serial transverse cryostat sections were processed using conventional histological stains and histochemical reactions , as previously described . immunohistochemistry was performed for dystrophin ( n - terminus , rod domain , and c - terminus , novocastra , uk ) , -sarcoglycan ( novocastra , uk ) , -sarcoglycan ( novocastra , uk ) , -sarcoglycan ( novocastra , uk ) , -sarcoglycan ( novocastra , uk ) , dysferlin ( novocastra , uk ) , merosin ( novocastra , uk ) , emerin ( novocastra , uk ) on frozen , acetone - fixed sections , and later on for -dystroglycan ( clone via4 - 1 , upstate biotechnology , usa ) on formalin fixed and paraffin embedded tissue . frozen muscle samples ( 20 to 30 mg ) were quickly weighed and homogenized with 1 laemmli buffer . the samples were incubated at 95 c for 10 min and centrifuged at 13,200 g for 1 min before 10 l aliquots of the supernatants ( equivalent to 2.5 mg tissue ) were applied to each lane . the following antibodies were used : mouse monoclonal antibodies against caveolin-3 ( santa cruz , usa ) , lamin a / c ( santa cruz , usa ) , telethonin ( bd biosciences , austria ) , calpain-3 ( leica , germany ) and -dystroglycan ( millipore , austria ) as well as horseradish - conjugated goat anti - mouse immunoglobulins ( dako , denmark ) . in order to define the molecular genetic basis of the disease regions of homozygosity in the lgmd2 patients , genomic dna samples from patients and unaffected sibs from families md1 and md2 , and a control sample were hybridized to genechip human mapping 10 k xbai 142 2.0 arrays ( affymetrix , santa clara , ca , usa ) using the protocols recommended by the manufacturer . samples from patient md2 , her healthy sib , and from a healthy control were subsequently also hybridized to genechip human mapping nspi 250 k arrays . genotypes of both array types were called using genechip genotyping analysis software ( version 4.1 ) and default thresholds . the overall call rate of each array succeeded 95% or more . the snp results of family md1 and md2 were then further analyzed using a self developed java - based tool ( ehopasa easy homozygosity profiling of affymetrix snp arrays ) which had been designed to quickly extract genome wide regions of homozygosity which may harbor the disease gene . the software accepts affymetrix snp array data and generates result files with homozygosity profiles , as well as the underlying genotyping data for these files . single occurrences of genotyping failure discovered as heterozygosity , or undetermined genotypes ( no calls ) , are ignored when at least seven neighboring genotypes on each side are homozygous . we arbitrarily defined a homozygous region on the occurrence of at least 5 or more consecutive homozygous snps ( 10 k array ) and 50 snps ( 250 k array ) by the user - selectable parameter in the program . the generated homozygosity profiles were plotted across the entire human genome using the r statistical software package . in addition to other software programs our tool was adapted to quickly visualize the lgmd2 loci by inclusion of the physical positions of the lgmd2 loci and to use the local computer infrastructure . all analyses are based on human reference sequence hg 18 ( ncbi build 36 version 1 ) genome assembly annotations . the ehopasa software itself and r programming code for plotting of the homozygosity profiles will be freely available for download ( http://ehopasa.sourceforge.net ) . all exons and exon - intron bounderies of capn3 [ omim 114240 ] ( md1 ) and cav3 [ omim 601253 ] , ptrf [ omim 603198 ] and fkrp [ omim 606596 ] ( md2 ) were screened for mutations . pcr conditions were as follow : 20 ng of genomic dna , 5 l hotstartaq mastermix ( qiagen gmbh , hilden , germany ) and primer ( 10 pmol each ) in a total volume of 10 l . cycle conditions were as follows : initial denaturation for 12 min at 95 c ; 35 cycles of 45 s denaturation at 95 c , 30 s of annealing at 57 c and 30 s of primer extension at 72 c ; and a final extension for 10 min at 72 c . pcr products were purified with filter plates ( macherey - nagel gmbh & co. kg , dren , germany ) and directly sequenced with automated sequencer using bigdye terminator v3.1 ( abi 3730 genetic analyzer , applied biosystems , foster city , ca ) . sequencing analysis was carried out using the seqscape software 2.5 ( applied biosystems , foster city , ca ) . the two patients , whose healthy parents are first cousins , initially complained about running and walking difficulties and problems in climbing stairs starting at the age of 9 and 15 years , respectively . on examination there was symmetric weakness and wasting of the limb girdle muscles predominating in the pelvic girdle and in the proximal lower limbs muscles with the thigh adductors more severely affected than the quadriceps muscles . serum creatine kinase ( ck ) levels were markedly increased up to 5500 and 12,000 u / l ( normal values < 170 u / l ) . electromyography ( emg ) showed a chronic myopathic pattern and nerve conduction studies were within the normal range . , dna was collected from the parents , the two patients , and the healthy sibs after informed consent . a whole genome scan using 10 k affymetrix snp arrays we analyzed the haplotypes of the affected and unaffected sibs using our self developed tool to detect the homozygosity profiles of each individual . 1a , there is only one peak present in the affected sibs which overlaps with one of the known lgmd2 loci . this peak is located on chromosome 15 ( 3760789562926989 bp ) and contains the capn3 gene . capn3 sequencing identified the known homozygous c.483delg ( p.ile162serfsx17 ) mutation in exon 3 in the two affected children , for which the parents were heterozygous ( fig . this 26 year old female first noticed problems in climbing stairs and weakness in the proximal upper limbs muscles and mild to moderate cardiomyopathy appeared subsequently . muscle weakness and wasting were restricted to the proximal limb musculature and predominated in the lower limbs . she walked with a waddling gait and had mild scapula winging . rippling , mounding and ck levels were elevated up to 2000 u / l and emg confirmed a chronic myopathy . caveolin-3 immunostaining and western blotting indicated a complete loss of the caveolin-3 protein expression , whereas other muscle proteins were normal ( fig . 3b ) . however , sequencing of cav3 and ptrf , which had been reported to be associated with secondary caveolin-3 deficiency failed to detect a pathogenic mutation . subsequently , a more detailed family history revealed that the parents of the patient were second degree cousins . analysis of the 10 k snp array genotypes of the patient and her healthy sib identified two large homozygous regions at chromosomes 17 ( 3651882661670208 bp ) and 19 ( 3420606754914726 bp ) corresponding to the lgmd2d [ omim 608099 ] and lgmd2i [ omim 607155 ] loci ( fig . additional analysis of the denser 250 k snp array did not exclude any of these loci and did not detect further homozygous regions corresponding to known lgmd2 loci ( fig . re - examination of the patient 's muscle biopsy revealed pathologically aberrant glycosylation of -dystroglycan on the sarcolemma compared to a control muscle by immunoblotting ( fig . 3ab , ac ) . finally , sequencing of the fukutin related protein gene ( fkrp ) identified the common c.826 c > a ; ( p.leu276ile ) mutation ( fig . mri studies of the proximal muscles of the upper and lower limbs were consistent with previous findings in lgmd2i . individual diagnosis and classification of lgmd2 patients is challenging due to considerable intra- and inter - familiar clinical variability and genetic allelic and non - allelic heterogeneity with 15 disease genes known so far . in addition , an extensive diagnostic work - up including invasive muscle biopsy is usually required . in this study we present the successful application of snp - array based whole genome homozygosity mapping in the molecular genetic diagnosis of lgmd2 . we emphasize this form of indirect dna analysis as the first step in the approach to diagnose patients from families with known or suspected parental consanguinity , because it is fast , inexpensive , and amenable to high - throughput setting . in principle , the causality of several known lgmd2 genes can be excluded with high probability in patients that do not show extended homozygosity at these loci . because the patients included in this study originated from inbred populations lgmd2 caused by a homozygous mutation in one of the known lgmd2 genes was the most likely underlying genetic event . whole genome homozygosity mapping using the 10 k snp array was straightforward in the three patients examined here . a single large homozygous region , at the lgmd2a [ omim 253600 ] locus , was seen in both patients from family md1 , without genetic linkage and haplotype analyses , enabling a fast , non - invasive diagnosis following the sequence analysis of capn3 . the more distant parental relationship reduced both the number and the size of homozygous regions in patient md2 compared to patients from md1 . however , two homozygous regions overlapping with lgmd2 loci , were considered identical by descendent from a common ancestor because of their genomic size and extent in the number of homozygous markers ( fig . 1 ) . identification of a common , homozygous fkrp mutation established a diagnosis of lgmd2i , which was confirmed by aberrant muscle -dystroglycan staining ( figs . notably , the correct diagnosis in patient md2 was delayed due to the absent caveolin-3 protein expression leading to the initial suspicion of lgmd1c [ omim 607801 ] . although secondary protein deficiency documented by immunohistochemistry in muscles of lgmd patients is not unusual and may be misleading in the further diagnostic process , the finding of caveolin-3 deficiency is surprising , as has been demonstrated by a study suggesting that caveolin-3 protein deficiency is a highly sensitive and specific marker of primary caveolinopathy . however , secondary caveolin-3 deficiency has recently been reported in patients with lipodystrophy and muscular atrophy carrying mutations in ptrf . the underlying mechanism of the secondary caveolin-3 deficiency in our fkrp patient remains elusive , but may be due to the altered -dystroglycan glycosylation , which might interfere with the correct localization of caveolin-3 at the sarcolemma . therefore we suggest that lgmd2i should be considered in patients with absent caveolin-3 expression in skeletal muscle and normal results on cav3 sequencing . a recent study has demonstrated that high - density snp homozygosity mapping can also successfully be applied to non - consanguineous single individuals with rare autosomal recessive diseases , such as lgmd2 , considering the hypothesis that the disease is caused by a homozygous mutation located within a homozygous haplotype , being identical by descent from an unknown common ancestor . homozygous disease - causing mutations could be detected in single cases of outbred populations within homozygous areas often larger than 2 mb in size . on the other hand , homozygous genomic segments measuring up to 4 mb were not uncommon in individuals from outbred populations . although application of the 10 k snp array was sufficient to detect the disease - related homozygous regions in the patients examined here , only higher density snp arrays might allow the detection of the disease - related homozygous segments in cases of more distant or suspected parental relationship .
a large number of novel disease genes have been identified by homozygosity mapping and the positional candidate approach . in this study we used single nucleotide polymorphism ( snp ) array - based , whole genome homozygosity mapping as the first step to a molecular diagnosis in the highly heterogeneous muscle disease , limb girdle muscular dystrophy ( lgmd ) . in a consanguineous family , both affected siblings showed homozygous blocks on chromosome 15 corresponding to the lgmd2a locus . direct sequencing of capn3 , encoding calpain-3 , identified a homozygous deletion c.483delg ( p.ile162serfsx17 ) . in a sporadic lgmd patient complete absence of caveolin-3 on western blot was observed . however , a mutation in cav3 could not be detected . homozygosity mapping revealed a large homozygous block at the lgmd2i locus , and direct sequencing of fkrp encoding fukutin - related - protein detected the common homozygous c.826 c > a ( p.leu276ile ) mutation . subsequent re - examination of this patient 's muscle biopsy showed aberrant -dystroglycan glycosylation . in summary , we show that whole - genome homozygosity mapping using low cost snp arrays provides a fast and non - invasive method to identify disease - causing mutations in sporadic patients or sibs from consanguineous families in lgmd2 . furthermore , this is the first study describing that in addition to ptrf , encoding polymerase i and transcript release factor , fkrp mutations may cause secondary caveolin-3 deficiency .
the term myositis ossificans is not used anymore because primary muscle inflammation is not a necessary precursor and ossification does not always occur in muscle tissue . periarticular ho is seen in patients with traumatic brain injury , tetanus , gullian - barre syndrome , poliomyelitis , prolonged mechanical ventilation , severe trauma , hip arthroplasty and burns . central nervous system tuberculosis ( cns tb ) comprises about 10% of all tb cases . tubercular meningitis ( tbm ) is the most common form of cns tb , a subacute disease with high morbidity and mortality if left untreated . in survivors of tbm , neurological sequelae are common which may include hydrocephalus , cranial nerve palsies , stroke and associated neurological deficits , seizures , mental retardation , spasticity and coma . these numbers are likely to rise due to an increase in drug resistance , increased use of immunosuppressive therapies , and increase in incidence of hiv . a 35-year - old right - handed male was admitted with diagnosis of tbm with hydrocephalus with left - sided hemiparesis . history revealed loss of consciousness 15 months back following complaint of low grade fever of long duration . the patient regained consciousness after 1 week but was unable to move his left upper and lower limb . six months later , the patient developed progressive limitation of left hip and knee movement . a month later he suffered left shoulder pain during a physical therapy session , after which the patient and his caretakers stopped giving any therapeutic exercises due to severe pain on movements . physical examination revealed contractures over his left shoulder , hip and knee [ figure 1 ] with ankylosis of left hip and knee [ figures 2 and 3 ] . the radiographic examination revealed ectopic bone deposition around , left hip [ figure 2 ] , left knee [ figure 3]and left shoulder [ figure 4 ] . mri of pelvic region showed early avascular changes in bilateral hip with altered signal intensity involving the muscles along left hip joint and upper part of shaft of femur with extension to overlying subcutaneous tissue anteriorly . ( a ) patient with tbm and left - sided hemiparesis , ( b ) left hand deformity , ( c ) left hip and knee deformity with ankle equinus x - ray of patient showing extensive heterotopic ossification around left hip with ankylosis of left hip x - ray of left knee showing heterotopic ossification around knee joint : ( a ) ap view ( b ) lateral view the patient was managed conservatively with antitubercular drugs , nsaids for ho as maturation was not observed , left abduction orthosis with dynamic cock up splint [ figure 4 ] , turn buckle splint for left knee with anklet skin traction with derotation bar for deformity correction at left hip and knee . rehabilitation program included exercise programs , activities of daily living ( adl ) training , speech therapy and wheelchair training for ambulation . x - ray of the left shoulder in pa view in adducted ( a ) and abducted ( b ) position showing heterotopic ossification , with left abduction orthosis with left dynamic cock - up splint ( c ) reported ho at right hip joint and bilateral sternoclavicular joint in a patient of tubercular meningoencephalitis . incidence of this finding has not been reported in a large series , however , a study in children suffering from tbm revealed 5 out of 10 children being affected by ho . in tbm , ho mostly occurs around hip involving psoas major , adductor longus , adductor magnus , and pectineus and iliacus muscle . very rarely ho around shoulder is observed . complications of ho include neurovascular entrapments , skin breakdown , loss of range of motion ( rom ) and joint ankylosis . a common cause of neurogenic ho is spinal cord injury , where incidence ranges between 1.3% and 57% and is usually seen in the first 6 months after injury . risk factors for ho include older age , neurological complete lesion , male gender , spasticity , venous thrombosis and pressure sores . only joints below the neurological level of injury will develop heterotopic bone with the most common location being the hips , followed by the knees , then shoulders . ho at the knee rarely causes complete ankylosis , and therefore surgical excision may not be performed . however , ho does decrease the rom which impairs function . in their series of 17 patients with neurological injuries who had excision of ho around the knee observed that surgical excision of ho of the knee is an effective procedure for increasing joint mobility and function . ippolito et al . , evaluated the results of excision of areas of ho in five patients of traumatic brain injury followed by optimum rehabilitation and observed that all patients could walk and all knees were pain free . all knees had more than functional arc of motion and there was no recurrence of ho in any of the knees . diagnosis can be suspected by early clinical findings which include warmth , tenderness , and soft tissue swelling . swelling progresses to more firm and localized area over several days and may present with decreased rom of affected joint . plain x - ray films detect ho in 7 - 10 days after onset of clinical signs , whereas triple phase bone scan can detect ho 1 week from onset and precedes x - ray by 7 - 10 days . bone scan returns to normal as ho matures in 6 - 18 weeks post injury . serum alkaline phosphatase levels increases at 2 weeks , usually exceeds normal levels at 3 weeks , peaks at about 10 weeks and returns to normal after ho matures . nonsteroidal anti - inflammatory drugs like indomethacin and ibuprofen have been used both for prophylaxis and treatment of ho . bisphosphonates has been shown to decrease the rate of new bone formation in patients with ho ; however , it has no effect on bone which has already been deposited . radiation therapy has been reported to possibly act by interfering with differentiation of pleuripotent mesenchymal cells into osteoblasts . it also decreases pain perception by suppression of tissue inflammation and ablation of pain receptors . extracorporeal shockwave therapy has shown favorable results as a supplementary treatment along with physiotherapy and rehabilitation . surgical excision should be reserved in patients with intractable pain , severely limited rom that causes functional limitations ( hip rom less than 50% ) provided there is the absence of local fever , swelling , erythema , normal serum alkaline phosphatase levels and return of bone scan findings to normal or near normal . this patient had rigorous massage and forceful stretching of joints leading to left shoulder joint dislocation and ho . in india , in rural areas , it is a common practice to do unsupervised rigorous massage and stretching exercises in all paralyzed patients . moreover , lack of skilled therapists , unawareness and underutilization of health services add to the problem . very few reports have been published in literature for association of ho with tbm with such extensive joint involvement which compels us to report this clinical association of tbm . this report is intended to create caution among physicians and other caregivers for this debilitating complication of tbm and in face of high prevalence of tuberculosis and tbm , employ methods for prevention , early diagnosis and treatment .
tubercular meningitis is a severe form of central nervous system tuberculosis with high morbidity and mortality . apart from neurological deficits , musculoskeletal involvement is also seen in very few cases in the form of heterotopic ossification around immobile joints . a 35-year - old male case of tubercular meningitis with left hemiparesis presented with multiple joint restriction of range of motion . on clinical examination , palpable firm masses around multiple joints with painful restriction of movements were seen . x - ray films of multiple joints revealed heterotopic ossification over left shoulder , hip and knee joint with bony ankylosis of left hip and soft tissue contractures . very few reports have been published in the literature for association of heterotopic ossification with tubercular meningitis with such extensive joint involvement which compels us to report this clinical association of tubercular meningitis . this report is intended to create caution among physicians and other caregivers for this debilitating complication of tubercular meningitis and in face of high prevalence of tuberculosis and tubercular meningitis , employ methods to prevent and treat .
for a long time now , inflation has been the leading paradigm for the origin of cosmological structures . this is largely due to its continuing success in confrontation with a wide range of observations , but also due in part to its theoretical simplicity compared to rivals such as cosmic strings , both in terms of making predictions for the perturbations and in the form ( gaussian and adiabatic ) of perturbations generated . the interaction between observations and theoretical modelling of inflation plays a two - fold role in cosmology . the most - emphasized role is the possible use of observations , especially of cosmic microwave background anisotropies , to support or rule out the inflationary paradigm as the source of structures ( see liddle & lyth 1993 for a review ) . such a program may well offer the first glimpses of possible physics at very high energies . much less has been said about the second role of inflation that in providing a simple framework for structure formation , it is crucial in enabling the high - accuracy determination of more mundane cosmological parameters such as the hubble constant and the density parameter . i shall focus particularly on this aspect towards the end of this review . inflation is defined as any epoch of the universe s history during which the scale factor @xmath0 is accelerating . in fact , we have yet to prove conclusively that this is not happening at the present epoch , but here i am interested in whether such a behaviour might have happened in the universe s distant past . i actually prefer to use the hubble parameter @xmath1 to write this in a somewhat different way @xmath2 where dots are of course time derivatives . the quantity @xmath3 is the hubble length , the principal characteristic scale of an expanding universe , and dividing it by @xmath4 switches to comoving coordinates , i.e. the behaviour of relative to the expansion . in words , inflation is precisely the condition that the comoving hubble length is decreasing with time . since in comoving units all the objects just remain where they are as the universe expands , and since at any epoch the hubble length is a good estimate of how far light can travel during that epoch , this is telling us that inflation acts like a zoom lens , focussing in on an ever - tinier part of the initial region . that s why , for example , inflation can solve the flatness problem ; even if curvature is important initially , when we zoom in on a tiny region the curvature becomes negligible , and enough ` zooming ' can more than compensate for the subsequent increase of the comoving hubble length after inflation ends . inflation s ability to generate large - scale perturbations is all down to the behaviour of the hubble length , because it means that a given length scale may start well inside the hubble radius , but finish up well outside it . any irregularities existing at that time become ` frozen - in ' , unable to evolve . if we lived in a purely classical world , this would lead to a perfectly homogeneous universe , simply because the assumption that the initial energy density be finite requires that there can not be irregularities down to arbitrarily small scales . fortunately , we live not in a classical universe but a quantum one , and the uncertainty principle implacably opposes inflation s attempts to make a perfectly smooth universe . more so , it does this in a manner which is readily predictable for a given inflationary model . it turns out that quantum fluctuations give rise to two types of perturbations in the universe , density perturbations and gravitational waves . these both take on a classical character once they are on scales well in excess of the hubble length . in order to give definite predictions for these , it is necessary to have a definite model for the inflationary expansion rather than just the hand - waving sketch i ve given above . here i want to stress that inflationary model - building has become quite a complicated and sophisticated occupation , and in presentations like this one necessarily gives an oversimplified picture . bear that in mind , and i ll also remind you of it later . + the acceleration equation @xmath5 immediately tells us that we re going to need something a little out of the ordinary , namely @xmath6 . the standard way of achieving this uses a scalar field , the sort of thing which crops up all over the place in modern particle physics theories , especially when symmetry breaking is under consideration . the standard simplified picture , which does in fact cover a large fraction of the currently popular models , is that there is only one scalar field , and that it evolves classically by slow - rolling down a self - interaction potential @xmath7 such as that shown in figure [ scalpot ] . either of these assumptions can be altered , giving more complicated models , but the bulk of my discussion will stay with the simplest case . such a homogeneous scalar field has effective energy density and pressure @xmath8 and so the condition for inflation is satisfied as long as the potential dominates over the kinetic term . this will clearly happen if the potential is sufficiently flat ; in fact , the flatness condition is very weak and so inflation is quite generic . in principle , @xmath7 is predictable from fundamental theories of physics . in practice there is as yet no clear guidance , and instead we treat it as a free function to be constrained by observations . if the inflationary expansion is rapid enough , physical conditions during inflation will change little between the origin of perturbations on the largest interesting scales and the smallest , so as a rough rule of thumb we expect that the perturbations will be nearly scale - invariant . for a long time , the perturbations were indeed taken to have that form . however , more recently the observations have reached such quality that the scale - invariance approximation is no longer an adequate description , and we have to do better . this is in no way a set - back ( or climb - down ) for inflation it is an impressive success that the theory has done so well that we now regard small corrections to the initial picture as significant and observationally testable . the breaking of scale - invariance will depend on the form of the potential @xmath7 ( it being the only input information ) , so we quantify this by defining two slow - roll parameters ( liddle & lyth 1992 ) @xmath9 where prime means a derivative wrt @xmath10 , and @xmath11 is the planck mass . inflation requires that both these be less than one , in order to maintain dominance of the potential . the first measures the slope of the potential , the second its curvature . the terminology i will use is nt very important ; density perturbations are specified by @xmath12 and gravitational waves by @xmath13 where @xmath14 is the comoving wavenumber . for scale - invariant spectra these are both independent of @xmath14 ; the power spectrum @xmath15 . under the inflationary paradigm , these spectra are responsible for all the observed structures , with gravitational waves at best only significantly influencing large - angle microwave background anisotropies . the formulation i ll describe is based on a perturbative approach , where we expand the ( log of the ) spectra in terms of log(wavenumber ) about some scale @xmath16 : @xmath17 and truncate at some level . for example harrison zeldovich spectrum ( constant @xmath18 ) . power - law spectrum with spectral index @xmath19 . includes scale - dependence of the spectral index . current observations require at least the second term and normally people stop there . i ll return to the third one later . the second term gives the power - law approximation , and the observables can be very nicely computed in terms of the slow - roll parameters ( liddle & lyth 1992 ) : @xmath20 if slow - roll holds very well ( @xmath21 , @xmath22 ) we get scale - invariant density perturbations and negligible gravitational waves . note also that although @xmath23 is positive by definition ( the field always rolls downhill ) , @xmath24 can have either sign and @xmath19 can be greater or smaller than one . the final relation , giving the ratio of the spectra in terms of @xmath25 , is known as the consistency relation ; it represents the inevitable ` entanglement ' of the density perturbations and gravitational waves due to their common origin in the single function @xmath7 . in the unlikely event of it proving testable , it represents a very distinctive prediction of inflation . the cobe observations have a very simple interpretation in terms of inflation . because the cobe beam is so wide , it only probes scales larger than the horizon at the time of decoupling , so perturbations have not had time to evolve and are captured in their primordial form . in particular , the observed anisotropies do not depend on cosmological parameters such as the hubble constant @xmath26 and the baryon density @xmath27 . cobe determines the perturbation amplitude extremely well , to about 10% accuracy , but is unable to distinguish the effect of density perturbations and gravitational waves . its most useful application is to normalize the density perturbation spectrum ; bunn et al . ( 1996 ) obtained the result @xmath28}{\sqrt{1 + 0.75 r } } \,,\ ] ] using techniques described by bunn & white ( 1995 , 1997 ) . here @xmath29 is the perturbation amplitude at the present hubble radius , and @xmath30 approximately measures the relative importance of gravitational waves and density perturbations in generating the anisotropies . the factor 12.4 comes from analytic evaluation assuming only the sachs wolfe effect applies and perfect matter domination at last scattering ; that the above expression contains the factor 0.75 indicates that this approximation fails at the tens of percent level on cobe scales . cobe fixes the energy scale of inflation as ( bunn et al . 1996 ) @xmath31 where @xmath32 indicates the value when the observed perturbations were generated . for a specific model @xmath23 is known and so this can be given exactly . unless @xmath23 is tiny , which is perfectly possible in some models , the energy scale is around that expected of grand unification . the spectral index @xmath19 is only very weakly constrained by cobe , due to the limited range of scales sampled . nowadays , measured anisotropies go well beyond cobe , with a host of experiments reporting detections on a range of angular scales . figure [ cell ] shows a recent compilation by martin white . the data are encouragingly compatible with inflationary preconceptions , but unfortunately at present do nt allow us to say much more ; the predictions on smaller angular scales ( larger @xmath33 ) depend on all the cosmological parameters and the observational errors are larger than one desires . the compilation does indicate a lower limit on @xmath19 , which is somewhat model - dependent but is around @xmath34 , and at the moment that is its main inflationary implication . the upcoming launch of the map and planck satellites offers the prospect that cosmology could be more or less solved , in the sense that its most crucial parameters might be measured to a satisfyingly high accuracy ( jungman et al . 1996 ; bond et al . 1997 ; zaldarriaga et al . . however , there are rather a lot of parameters which might come into play . most attention has been focussed on the cosmological parameters , such as the hubble constant @xmath26 , total matter density @xmath35 , baryon density @xmath27 , cosmological constant @xmath36 , hot dark matter density @xmath37 and the optical depth to the last - scattering surface @xmath38 . some of these might be fixed by assumption , but as a very minimum @xmath26 , @xmath27 and @xmath38 must be determined observationally . however , in this article i want to turn attention to the inflationary input . as i stressed at the beginning , this is absolutely crucial as a paradigm in cosmology . if we do nt know the initial perturbation spectra , we have no chance of interpreting observed microwave anisotropies in terms of the cosmological parameters . this is potentially a very serious problem , since without guidance the perturbations could be free functions which need not be simple . fortunately , most models of inflation give very simple predictions , and are summarized in only two or three parameters , namely @xmath18 , @xmath19 and perhaps @xmath39 . however , scale - dependence of @xmath19 is possible , and in accordance with the taylor expansion of eq . ( [ taylor ] ) it can be incorporated by inclusion of derivatives @xmath40 , @xmath41 and so on . these represent extra parameters which must be determined from observations . if extra parameters are introduced , then the determination of _ all _ parameters will deteriorate . we have estimated the extent of this deterioration ( copeland et al . 1997 ) for a configuration of the planck satellite including polarized detectors . it is shown in table [ parest ] . llll parameter & + & + @xmath42 & @xmath43 & @xmath44 & @xmath45 + @xmath46 & @xmath47 & @xmath47 & @xmath48 + @xmath49 & @xmath50 & @xmath51 & @xmath52 + @xmath53 & @xmath54 & @xmath54 & @xmath54 + + @xmath55 & @xmath56 & @xmath50 & @xmath57 + @xmath58 & @xmath50 & @xmath51 & @xmath51 + @xmath40 & @xmath59 & @xmath60 & @xmath50 + @xmath61 & @xmath59 & @xmath59 & @xmath62 + we see that permitting scale dependence of @xmath19 primarily only affects the determination of @xmath19 , and not the other cosmological parameters , which is an encouraging conclusion . it suggests that if the modelling of inflation turns out to be over - simplified , the influence on parameter determination will not be too great . on the other hand , it is clear that @xmath19 can not be measured as well as has been claimed ( e.g. bond et al . 1997 ; zaldarriaga et al . 1997 ) unless it is _ assumed _ that the spectrum is a perfect power - law . now , as promised , i turn to the question of possible complications to the inflationary modelling . first of all , one can ask whether we are in a position to compute the perturbations at the 1% or so accuracy level demanded by map and planck . finally , the answer to this appears to be ` yes ' ; the last problem ( gravitational waves in open universe models see below ) has been solved during the last year and there are no existing models in which the perturbations can not be computed , at least through numerical integration of the relevant mode equations , to the required accuracy . so far we ve been sticking to models with a single scalar field , with @xmath7 kept as a free function . normally the slow - roll approximation gives a very accurate analytic result ( grivell & liddle 1996 ) . however , a sufficiently complicated potential may lead to a failure of slow - roll severe enough that the slow - roll approximation is not good enough ( wang et al . 1997 ) , and the numerical results are required . however , we have found ( copeland et al . 1998 ) that this need not be a bad thing ; in particular , the near - failure of slow - roll makes it far more likely that the scale - dependence of @xmath19 is observable , which allows one to determine more information about the inflaton potential than would otherwise have been available . further , it would take a bizarre conspiracy for the slow - roll approximation to be failing , but yet for us to be oblivious to this . if things are going wrong to the extent that numerical computation is needed , we will know it . the main worry in fact for the single - field models described so far is that many models [ particularly those constructed under the currently - popular hybrid inflation strategy ( see lyth 1996 for a review ) ] predict a negligible level of gravitational waves . this limits seriously the amount of information that can be inferred about @xmath7 , which can not even be determined uniquely if the gravitational waves can not be detected . it is certainly possible that more than one scalar field can be dynamically important , and this can lead to a range of new phenomena . the perturbations may have an isocurvature component as well as the usual adiabatic one , and may even be non - gaussian . the perturbations can still be computed accurately , but now only on a model - by - model basis rather than via an all - encompassing formalism like that i ve demonstrated for single - field models . this makes it much harder to ` guess ' viable models from the observations . however , calculational complications aside , a specific model of this type is as easy to exclude using observations as a single - field model . open inflation models are an unfortunate late addition into the inflationary model zoo . although dating back almost to the beginnings of inflation ( gott 1982 ) , it is only relatively recently that they have been appreciated as a serious model . they rely on quantum tunnelling to generate an open universe within an inflationary sea . for a long time the perturbations in these models could not be computed ( especially the gravitational waves ) , but finally the technology is in place ( sasaki et al . 1997 ; bucher & cohn 1997 ) , and predictions can be obtained from them as readily as the more conventional models . mathematically they are much nastier models ( for example the mode functions on hyperbolic geometry are very unpleasant indeed ) than ones giving a flat spatial geometry . fortunately , the spatial geometry is very readily measurable , even before the satellites go up , and hopefully these models will soon be consigned to the dustbin . if inflation is not in fact the correct theory for the origin of perturbations , this should be obvious from the observations . the inflationary prediction of passive , super - horizon perturbations is very distinctive , and leads to the familiar oscillations in the radiation angular power spectrum . if inflation is correct the observations should highly overdetermine the various parameters of the big - bang model , reassuring us that we are on the right track . but here is a good point to stress once more the importance of inflation as a paradigm for the initial conditions . for example , it seems rather unlikely that predictions at the one percent level could come from the rival topological defect scenario in the forseable future , due to the horrendous non - linearities involved in the computations . without accurate theoretical predictions for the anisotropies , huge extra uncertainties enter the cosmological parameter estimation game and severely dent one s ability to measure any of them . my main point of emphasis has been to stress that the inflationary paradigm is a crucial underpinning of attempts to measure cosmological parameters from the microwave background . it provides a framework in which accurate predictions can readily be made , enabling the maximum to be squeezed out of quality observations . we are fortunate indeed that not only is the model theoretically appealing , but that it also stands in excellent shape when confronted with present data . we can only hope that in ten years time , when the large zoo of inflation models have been confronted with the new observations , that things may still look so good . i was supported by the royal society . thanks to ted bunn , ed copeland , ian grivell , rocky kolb , david lyth and martin white for their collaboration in parts of the work described here , and to martin white for providing the data compilation shown in figure [ cell ] . bond , j.r . , efstathiou , g. and tegmark , m. , 1997 , mon . not . . soc . * 291 * , l33
i give a status report and outlook concerning the use of the cosmic microwave background anisotropies to constrain the inflationary cosmology , and stress its crucial role as an underlying paradigm for the estimation of cosmological parameters . 9.1 in 6.3 in -30pt epsf sussex - ast 98/1 - 1 + astro - ph/9801148 + andrew r. liddle + _ astronomy centre , university of sussex + falmer , brighton bn1 9qh , united kingdom .
in the past decades , electronic components have become continuously smaller and reached the nanoscale . at these scales , electron transport can no longer be understood on purely classical grounds but quantum mechanical effects , such as , for example , the quantization of energy levels , quantum interference effects and tunneling processes need to be taken into account . single - molecule junctions , where a molecule is contacted by two macroscopic ( in most cases , metallic ) electrodes , represent prime examples of nanoelectronic devices . these junctions allow to investigate molecules under controllable nonequilibrium conditions and may facilitate an ultimate step in the miniaturization of nanoelectronic devices @xcite . it is thus highly desirable to understand the electron transport properties of these junctions . experimental studies employing a variety of techniques , such as mechanically controlled break junctions @xcite , scanning tunneling microscopy @xcite and electromigration @xcite , have shown that molecular junctions exhibit a large variety of interesting transport phenomena , including , for example , switching @xcite , negative differential resistance @xcite , diode- and/or transistor - like behavior @xcite . many of these transport properties are not fully understood yet . on one hand , this is due to ambiguities in the contact geometry , which may lead to large variations in the recorded current - voltage characteristics @xcite . while strategies to control the contact geometry exist , for example , by the use of special linker groups @xcite , direct binding schemes @xcite , or click - chemistry approaches @xcite , the electrodes themselves may show irregular behavior . it is therefore expedient to identify transport properties of molecules that are robust with respect to the contact geometry of the contact , such as , for example , inelastic electron tunneling spectra @xcite ) . on the other hand , electron transport through a molecular conductor represents a complex many - body problem , where , aside from multiple electronic states , the coupling to numerous vibrational degrees of freedom has to be taken into account @xcite . in contrast to other nanoelectronic devices ( _ e.g. _ quantum dots @xcite ) , electronic - vibrational coupling is typically rather strong in molecular systems . this is due to their small size and mass and can lead to pronounced vibrational effects in the respective transport characteristics @xcite . thereby , the interplay of electronic and the vibrational degrees of freedom of a molecular conductor often involves strong nonequilibrium @xcite as well as quantum mechanical effects @xcite . a fundamental quantum mechanical effect is quantum interference . the occurrence and observability of quantum interference effects in electron transport through molecular junctions has received great attention recently @xcite . quantum interference effects in molecular junctions arise because , very similar to a double - slit experiment , an electron may take different pathways through a molecule . thereby , pathways can be spatially different paths in molecules with an appropriate topology and/or originate from different paths in energy space , _ e.g. _ , for molecules that exhibit quasidegenerate electronic states @xcite . recently , strong experimental evidence for quantum interference effects in molecular junctions has been reported @xcite . moreover , quantum interference effects have been observed in the closely related field of electron transport through quantum dots that are set up as aharonov - bohm interferometers @xcite . depending on the magnetic flux that is threading the quantum dot , the transmission amplitudes of the electrons interfere constructively or destructively with each other , leading to sizable oscillations in the conductance of such a device @xcite . a great deal of theoretical work @xcite has been devoted to study quantum interference effects in molecular junctions , which is , on one hand , due to their fundamental importance but , on the other hand , also due to possible device applications , such as , for example , in transistors @xcite , thermoelectric devices @xcite or spin filters @xcite . thereby , in most of the studies , the effect of electron - electron interactions and electronic - vibrational coupling has been neglected . in this article , we investigate the influence of electronic - vibrational coupling on quantum interference effects in single - molecule junctions . thereby , we extend our earlier studies @xcite and analyze in detail the mechanism of vibrationally induced decoherence . moreover , we consider the effect of local cooling by electron - hole pair creation processes and show how these processes facilitate a mechanism that allows to control quantum interference effects by an external parameter , that is , the temperature of the electrodes . only recently , this mechanism has been experimentally verified by ballmann _ et al . _ @xcite for a number of different junctions , including different molecular species . note that , in contrast to refs . , we do not consider the vibrational degrees of freedom as being part of a thermal bath but , on the contrary , as active degrees of freedom . for our studies , we employ a nonequilibrium green s function approach developed by galperin _ et al . _ @xcite , which was recently extended by some of us to account for multiple vibrational @xcite as well as multiple electronic degrees of freedom @xcite . the approach is based on a separation of electronic and vibrational time scales and , therefore , allows a nonperturbative description of electronic - vibrational coupling as it is required in this nonequilibrium transport problem . moreover , it suits to describe quasidegenerate levels , which exhibit pronounced quantum interference effects . besides this approach , a variety of other methods has been developed to describe vibrationally coupled electron transport through nanoelectronic devices . this includes other nonequilibrium green s function approaches , which are based on either perturbation theory @xcite or nonperturbative schemes @xcite , scattering theory @xcite , master equation methodologies @xcite and a number of numerically exact schemes @xcite . the article is organized as follows : in sec . [ hamiltonian ] , we introduce the model hamiltonian that we use to describe vibrationally coupled electron transport through a single - molecule junction . the nonequilibrium green s function approach , which we employ to calculate the corresponding transport characteristics , is outlined in sec . [ negfapproach ] . in sec . [ basintsec ] , we introduce and analyze in detail the basic quantum interference effects that occur in single - molecule junctions . this facilitates the discussion of the effect of vibrationally induced decoherence in the following sections , secs . [ sequtunreg ] [ anomal ] . thereby , we study first simplified electronic - vibrational coupling scenarios that allow to investigate basic decoherence phenomena due to vibrations in the resonant ( sec . [ sequtunreg ] ) and the non - resonant transport regime ( sec . [ cotuneffects ] ) . in addition , we also discuss results for more realistics coupling scenarios . in secs . [ localcool ] and [ anomal ] , we show the importance of cooling by electron - hole pair creation processes in the presence of strong destructive quantum interference effects and how this cooling mechanism can be used to control interference effects by varying the temperature of the electrodes . we consider quantum interference effects and vibrationally induced decoherence in electron transport through a single molecule that is bound to two metal leads @xcite . this transport problem can be described by a set of discrete electronic states , which are localized on the molecular bridge ( m ) , and a continuum of electronic states , which are localized in the left ( l ) and the right ( r ) lead , respectively . thereby , the states on the molecular bridge are coupled to the states in the leads . the corresponding model hamiltonian can be written as @xcite @xmath0 where the @xmath1 denote the energies of the lead states and @xmath2 and @xmath3 the corresponding creation and annihilation operators . similarly , the @xmath4th electronic state on the molecular bridge is addressed by the creation and annihilation operators @xmath5 and @xmath6 , while its energy is given by @xmath7 . coulomb interactions may give rise to additional charging energies . these energies are accounted for in @xmath8 by hubbard - like electron - electron interaction terms , @xmath9 . , @xmath10 etc . need to be determined with respect to a reference state ( see refs . @xcite ) . for the effects and mechanisms that are described below , it is , however , not decisive whether the states are located above or below the fermi level of the junction . ] in principle , the index @xmath4 distinguishes different molecular orbitals , including the spin of the electrons . however , as interference effects occur only for transport through orbitals with the same spin , we suppress the spin degree of freedom in the following . the coupling matrix elements @xmath11 in the fourth term of @xmath12 characterize the strength of the interaction between the electronic states of the molecular bridge and the leads and determine the so - called level - width functions @xmath13 ( @xmath14=l , r ) . modeling the leads as semi - infinite tight - binding chains with an internal hopping parameter @xmath15ev , these functions are given by @xcite @xmath16 where , similar to @xmath11 , the parameters @xmath17 denote the coupling strength of state @xmath4 to lead @xmath14 . thereby , following refs . @xcite , we assume a symmetric drop of the bias voltage @xmath18 at the contacts , _ i.e. _ the chemical potentials in the left and the right lead are given by @xmath19 and @xmath20 , respectively . note that throughout the paper , the fermi energy of the leads is set to @xmath21ev . applying a bias voltage an electrical current is flowing through the junction . the molecular bridge may respond to this current , in particular , to the fluctuations of its charge state , which are induced by the tunneling electrons , by adapting its geometrical structure . if the equilibrium positions of the nuclei are different in the different charge states that are probed by the transferred electrons ( which is usually the case ) , transitions between the different vibrational levels become available , and the vibrational degrees of freedom of the junction may be excited according to the standard franck - condon picture @xcite . the vibrational degrees of freedom are described in our model as harmonic oscillators that are linearly coupled to the electron densities @xmath22 on the molecular bridge @xcite , @xmath23 where the operator @xmath24 denotes the creation operator of the @xmath25th oscillator with frequency @xmath26 and @xmath27 the corresponding vibrational displacement operators . the respective coupling strengths are denoted by @xmath28 . finally , the hamiltonian of the overall system is given by the sum @xmath29 for the nonequilibrium green s function approach that we use in this article ( cf . sec . [ negfapproach ] ) , it is expedient to remove the direct electronic - vibrational coupling term in the hamiltonian @xmath30 . to this end , we employ the small polaron transformation @xcite @xmath31 with @xmath32 , \end{aligned}\ ] ] and @xmath33 the momentum operator associated with vibrational mode @xmath25 . note that , although there is no explicit electronic - vibrational coupling in @xmath34 , it appears in the transformed hamiltonian @xmath34 at three different places : @xmath35 ) in the polaron - shifted energies @xmath36 , @xmath37 ) in additional electron - electron interactions , which add to the original electron - electron interaction terms @xmath38 and @xmath39 ) in the molecule - lead coupling term @xmath40 , which is renormalized by the shift operators @xmath41 . because we focus in this article on the effect of electronic - vibrational coupling on the transport characteristics of a single - molecule junction , we suppress the effect of electron - electron interactions in the following , that is we set the renormalized electron - electron interaction strengths @xmath42 to zero . a discussion of the effect of electron - electron interactions on the transport characteristics of a molecular junction can be found , for example , in our earlier work , refs . , or in refs . . in this context , it is interesting to note that for high bias voltage and within the wide - band approximation , electron - electron interactions have no substantial influence on the electrical current . this was shown by gurvitz and prager @xcite based on their exact microscopic rate equation methodology . at small ( finite ) bias voltages , however , it has already been demonstrated that in the presence of electron - electron interactions quantum interference effects become quenched by spin - flip processes @xcite . we like to stress that these effects are interesting on their own and very important , but that they are beyond the scope of this work . the central quantities in ( nonequilibrium ) green s function theory are the single - particle green s functions , which are given for the electronic degrees of freedom by @xmath43 they allow to calculate all single - particle observables , such as , _ e.g. _ , the population of levels or the current flowing through the junction . we employ the following ansatz to calculate these green s functions @xcite : @xmath44 with the electronic green s functions @xmath45 and @xmath46 the time - ordering operator on the keldysh contour . thereby , the indices @xmath47 indicate the hamiltonian that is used to evaluate the respective expectation values . the effective factorization of the single - particle green s functions @xmath48 into a product of the electronic green s functions , @xmath49 , and a correlation function of shift operators , @xmath50 , is justified , if the dynamics of the electronic and the vibrational degrees of freedom take place on different time scales . this is conceptually similar to the born - oppenheimer approximation @xcite . in the present context , however , we do not address the adiabatic regime , where the born - oppenheimer approximation applies , but rather the opposite regime , that is the anti - adiabatic regime , where the time scales for electron tunneling events are much longer than the ones for vibrational motion such that the nuclei of the molecule can follow the corresponding charge fluctuations . employing the equations of motion for the electronic green s functions @xmath49 , @xmath51 the respective self - energies due to the coupling of the molecule to the left and the right leads , @xmath52 and @xmath53 , can be obtained . these self - energies are given to second order in the molecule - lead coupling by @xmath54 where @xmath55 denotes the free green s function associated with lead state @xmath56 . the real - time projections of these self - energies determine the electronic part of the single - particle green s functions @xmath48 . in the energy domain the corresponding dyson - keldysh equations read @xmath57 with @xmath58 where @xmath59 denotes a positive infinitesimal number . note that eqs . ( [ eldy ] ) and ( [ elke ] ) give the exact result in the non - interacting limit , that is for @xmath60 , as well as for an isolated molecular bridge , where @xmath61 . besides the electronic green s functions @xmath49 , we also need to evaluate the correlation functions of the shift operators , @xmath62 , in order to obtain the full single - particle green s functions @xmath48 . to this end , we use a second - order cumulant expansion in the dimensionless coupling parameters @xmath63 @xcite @xmath64 with the momentum correlation functions @xmath65 employing the equation of motion for @xmath66 @xmath67 we determine the corresponding self - energy matrix @xmath68 . the self - energy matrix @xmath68 , which describes the interactions between the vibrational modes and the electronic degrees of freedom of the molecular bridge , is evaluated up to second order in the molecule - lead coupling @xcite @xmath69 since @xmath68 depends on the electronic self - energies @xmath70 and green s functions @xmath49 , eqs . ( [ elselfen ] ) ( [ piel ] ) constitute a closed set of coupled nonlinear equations that needs to be solved iteratively in terms of a self - consistent scheme @xcite . with the green s functions @xmath66 and @xmath48 , the average vibrational excitation of each vibrational mode is obtained according to @xcite @xmath71 -\frac{1}{2 } + \sum_{m}\frac{\lambda_{m\alpha}^{2}}{\omega_{\alpha}^2}\text{im}[\bar{g}^<_{mm}(t=0 ) ] \\ & & + 2\sum_{m < n}\frac{\lambda_{m\alpha}\lambda_{n\alpha}}{\omega_{\alpha}^2}\text{im}[\bar{g}^<_{mm}(t=0)]\text{im}[\bar{g}^<_{nn}(t=0 ) ] \nonumber\\ & & -2\sum_{m < n}\frac{\lambda_{m\alpha}\lambda_{n\alpha}}{\omega_{\alpha}^2}\text{im}[\bar{g}^<_{mn}(t=0)]\text{im}[\bar{g}^<_{nm}(t=0 ) ] , \nonumber \end{aligned}\ ] ] where we use the hartree - fock factorization @xmath72 for @xmath73 . the current is calculated employing the meir - wingreen - like formula @xcite @xmath74 note that this expression includes a factor of two to account for spin degeneracy . in this section we discuss quantum interference effects and vibrationally induced decoherence in single - molecule junctions based on the methodology introduced above . thereby , we consider models of increasing complexity . first , in sec . [ basintsec ] , we discuss the basic quantum interference effects that occur in electron transport through single molecules . thereby , we introduce the framework and the methodology that we use to analyze quantum interference effects in general . next , in secs . [ sequtunreg ] and [ cotuneffects ] , we study the effect of electronic - vibrational coupling on the transport characteristics of a single - molecule contact . thereby , we use both simplified coupling scenarios , which facilitate the interpretation of the results and provide a first understanding of the effect of vibrationally induced decoherence , and more complex ( yet more realistic ) scenarios , which , nevertheless , can be understood on the same grounds . finally , in secs . [ localcool ] and [ anomal ] , we discuss the effect of local cooling due to electron - hole pair creation processes , which , in the presence of strong destructive quantum interference effects , can become dominant ( sec . [ localcool ] ) . as will be shown in sec . [ anomal ] , this results in a strong temperature dependence of the electrical current that can not be explained in terms of the temperature dependence of the fermi distribution functions in the leads @xcite . the parameters for all the models employed in this article are summarized in tab . [ parameters ] . they have been chosen to represent typical values for molecular junctions and are similar to those employed in a number of first - principles studies of molecular junctions @xcite . it should be noted that we consider only models , where the coupling between the molecule and the electrodes is rather weak , i.e. , where the effective factorization of the single - particle green s functions , eq . ( [ decoupling ] ) , is valid . to this end , the coupling parameter @xmath75 , which determines the molecule - lead interaction strengths ( see tab . [ parameters ] ) , has been chosen as @xmath76ev , meeting the condition for the antiadiabatic approximation ( [ decoupling ] ) : @xmath77 . @xmath78&&&@xmath79&&&@xmath80 & & & @xmath81&&&@xmath82&&&@xmath83 & & & @xmath84&&&@xmath85&&&@xmath86 & & & @xmath87 & + & des & & & 0.5&&&0.505&&&0&&&@xmath75&&&@xmath75&&&-@xmath75&&&&&&&&& & & & 2 & + & con & & & 0.5&&&0.505&&&0&&&@xmath75&&&@xmath75&&&@xmath75&&&&&&&&& & & & 2 & + & desvib & & & 0.5&&&0.53&&&0&&&@xmath75&&&@xmath75&&&-@xmath75&&&0.1&&&0&&&0.05 & & & 2 & + & convib & & & 0.5&&&0.53&&&0&&&@xmath75&&&@xmath75&&&@xmath75&&&0.1&&&0&&&0.05&&&2 & + & desvib2 & & & 0.52401&&&0.53&&&0.049&&&@xmath75&&&@xmath75&&&-@xmath75&&&0.1&&&0.049&&&0.05 & & & 2 & + & descool & & & 0.05123&&&0.05126&&&0.00248&&&@xmath88&&&@xmath88&&&-@xmath88&&&0.005&&&0.00248&&&0.0025&&&0.25 & + quantum interference effects can be constructive or destructive , depending on the model , the physical parameters and/or the specific observable . in this section , we study basic interference effects for two different models of single - molecule junctions . the first model exhibits pronounced destructive interference effects in its conduction properties and is referred to as model des . the second model , con , shows constructive interference effects . note that both systems have been extensively studied before @xcite . they are thus very useful to set the stage for the discussion of vibrationally induced decoherence , which is presented in the subsequent sections , secs . [ sequtunreg ] [ anomal ] . it is also noted that similar models have been used to study interference effects in quantum dot arrays , in particular in the context of aharonov - bohm interferometers @xcite . interference effects arise in electron transport through molecular junctions whenever electrons can traverse the junction along different but equivalent pathways . this is the case , for example , if the electrical current of a junction is carried by two quasidegenerate electronic states . the first model system that we study , model des ( see tab . [ parameters ] for a summary of the respective parameters ) , comprises two electronic states , which are located at @xmath89ev and @xmath90ev above the fermi level of the junction . both of these states are coupled to the left lead with coupling strengths @xmath91ev and to the right lead with coupling strengths @xmath92ev and @xmath93ev , respectively . these coupling strengths , in particular the different sign in the coupling to the right lead , reflect the different spatial symmetry of the two states , which represent symmetric and antisymmetric combinations of localized molecular orbitals ( see figs . [ linconduct]a and [ linconduct]b for a graphical representation of the two electronic states and the corresponding localized molecular orbitals ) . the coupling to the electrodes induces a broadening of the two states of @xmath94mev that exceeds their level spacing @xmath95mev , _ i.e. _ they are quasidegenerate . [ cols= " < , < , < , < " , ] in the present context , it is important to note that in model desvib inelastic transport processes are not suppressed by destructive quantum interference effects due to the specific electronic - vibrational coupling scenario in this junction ( _ i.e. _ because @xmath96 ) . therefore , we consider another model system in this section , model desvib2 . it is very similar to model desvib but , in contrast , includes electronic - vibrational coupling also in state @xmath97 : @xmath98 but @xmath99 ( see tab . [ parameters ] for a complete list of parameters ) . as a consequence of the coupling to both states , inelastic transport processes are , similar to electronic transport processes , also suppressed by destructive quantum interference effects . in contrast , however , electron - hole pair creation processes are not suppressed , because they involve the coupling of an electronic state to just one of the electrodes and not to both , and , even if the respective coupling strength is negative , its square is not . this has a strong impact on the excitation levels of junction desvib2 . the corresponding vibrational excitation characteristic is shown in fig . [ figcoolingbyint ] by the solid black line . it exhibits very similar features as the one shown by model desvib but approximately only half of the corresponding vibrational excitation levels ( cf . [ decoherenceseqtunlinearfig]b ) . this is related to the fact that inelastic transport processes are suppressed by destructive quantum interference effects in this system while electron - hole pair creation processes are not . thus , the ratio between heating and cooling processes , which is typically between 1:2 or 1:1 for resonant electron transport through a single electronic state @xcite , is shifted towards much lower values , resulting in much lower levels of vibrational excitation . this cooling effect is even more pronounced , if the level spacing between the two electronic states is smaller and , consequently , the suppression of inelastic transport processes is more pronounced . the solid blue and red line in fig . [ figcoolingbyint ] , for example , show the excitation characteristics of model desvib2 for smaller splittings of the ( polaron - shifted ) energy levels . the corresponding excitation levels are substantially smaller . the only major contribution that remains in the limit @xmath100 is the one due to the formation of a polaronic state , @xmath101 ( cf . ( [ formulavibex ] ) ) . this , however , is only a static contribution that originates from charging processes and can not be used in deexcitation processes . in other words , the current - induced excitation of the vibrational mode is almost completely suppressed in this limit . l having in a mind that states @xmath97 and @xmath102 of model desvib2 may represent just symmetric and antisymmetric combinations of localized molecular orbitals ( see figs . [ linconduct]a and [ linconduct]b ) , their electronic structure may be very similar and , accordingly , also the respective electronic - vibrational coupling strengths . indeed , such pairs of electronic states are often found in realistic models of single - molecule junctions @xcite . the cooling mechanism described in this section can , therefore , be expected to occur in a large variety of single - molecule junctions . in sec . [ localcool ] , we have shown that electron - hole pair creation processes facilitate an important cooling mechanism for the vibrational degrees of freedom of a single - molecule contact @xcite , particularly in the presence of strong destructive quantum interference effects . within the local representation of the linear molecular conductor by two localized molecular orbitals ( as in fig . [ linconduct]b ) , this can be understood in an alternative way : if the intramolecular coupling @xmath103 becomes very weak , @xmath104 , the left and the right part of the molecular conductor decouple . in that sense , the two parts of the molecule behave as being part of the left or right electrode , that is they also acquire the same equilibrium state . this thermalization is facilitated by electron - hole pair creation processes and is comparable to the thermalization of a molecule adsorbed on a surface with the substrate . thus , the temperature in the electrodes can be used to control the excitation levels of the vibrational modes of the left and the right part of such a molecular conductor . moreover , as higher levels of vibrational excitation enhance the effect of vibrationally induced decoherence ( see sec . [ sequtunreg ] ) , the temperature in the electrodes can , in turn , be used to control quantum interference effects in single - molecule junctions . this will be demonstrated in this section . in general , a variation of the temperature of the electrodes is accompanied by a change in the contact geometry of a single - molecule contact , either due to thermal expansion of the electrodes or irreversible drifts of single gold atoms . in experiments , the stability of the contact geometry can often only be maintained for low temperature variations @xcite . in order to demonstrate control of quantum interference effects via the temperature of the electrodes , we therefore consider a model of a single - molecule contact that includes low - frequency vibrational modes , which , in the given range of temperatures , exhibit significant changes in their excitation levels . to this end , we consider a mode with a frequency of @xmath105mev , which represents a frequency value at the lower end of the vibrational spectrum of a larger molecule @xcite . moreover , we use a range from @xmath106k to @xmath107k for the temperature of the electrodes in the following , where the corresponding excitation level of the vibrational mode varies between @xmath108 and @xmath109 , respectively . this model system is referred to as model descool ( see tab . [ parameters ] for a complete list of parameters ) . besides the low - frequency mode , it includes two electronic states that are almost degenerate , that is @xmath110 . the current - temperature characteristic of this model systemmev significantly smaller than the frequency of the vibrational mode @xmath105mev in order to ensure the validity of the effective factorization of the single - particle green s function , eq . ( [ decoupling ] ) . while this is a prerequisite for our nonequilibrium green s function formalism , the underlying physical processes described in this section are effective also for larger molecule - lead coupling strengths . ] and the corresponding level of vibrational excitation are shown by the solid black lines in fig . [ figtempdep ] . thereby , we have used a bias voltage of @xmath111ev@xmath112 , which corresponds to the resonant transport regime of this junction . note that , at this bias voltage , the current level of junction descool is influenced neither by the thermal broadening of the fermi distribution functions in the leads @xcite nor vibrational sidepeaks that are associated with the onset of resonant excitation processes ( fig . [ basmech]a ) . as can be seen in fig . [ figtempdep ] , however , the current and the excitation level of the vibrational mode increases substantially with the temperature in the electrodes . we attribute this behavior to the quenching of destructive quantum interference effects by inelastic transport processes , which is enhanced , via the thermalization mechanism described above , for higher temperatures of the electrodes . this shows that the temperature in the electrodes can be used to control destructive quantum interference effects in a single - molecule junction . note that , very recently , this control mechanism has been demonstrated by ballmann _ et al . _ in mechanically controlled break junction experiments for a variety of different molecules @xcite . l ( a ) + + ( b ) + it is interesting at this point to study the temperature dependence of model descool for different absolute values of the electronic - vibrational coupling strengths @xmath85 and @xmath86 . thereby , as we have seen in sec . [ sequtunreg ] , it is expedient to keep the difference in the dimensionless couplings constant , _ i.e. _ @xmath113 . accordingly , the solid blue / green lines in fig . [ figtempdep ] represent the temperature characteristics of model descool that we obtain by reducing / increasing the two coupling strengths by @xmath97mev . these results corroborate that vibrationally induced decoherence is , to a large extent , driven by nonequilibrium effects ( see , e.g. , the discussion at the end of sec . [ sequtunreg ] ) , because for smaller electronic - vibrational coupling strengths we find lower levels of vibrational excitation and , due to the consequently less effective quenching of destructive interference effects , a more pronounced suppression of the current level . as a result , the relative temperature dependence @xmath114 is stronger for weaker electronic - vibrational coupling strengths in this system . it should be noted at this point that , in systems where destructive interference effects are not active , weaker electronic - vibrational coupling is typically associated with larger levels of vibrational excitation @xcite . this counterintuitive phenomenon is related to the suppression electron - hole pair creation processes , which , in the resonant transport regime , is more pronounced for higher bias voltages but also for weaker electronic - vibrational coupling . this suppression of pair creation processes is counterbalanced in transport through junction descool due to the presence of destructive interference effects . we have investigated the role of vibrations in electron transport through single - molecule junctions , which are governed by strong quantum interference effects . to this end , we have employed both analytical and numerical results that are obtained from nonequilibrium green s function theory @xcite . our results show that electronic - vibrational coupling has a strong and non - trivial influence on the transport properties of a molecular conductor , in particular , if quantum interference effects play a dominant role . this has been demonstrated by investigating models of molecular junctions , where pronounced quantum interference effects arise due to the existence of quasidegenerate states . on one hand , these states provide different pathways for a tunneling electron , which gives rise to strong interference effects in the respective transport properties . on the other hand , however , each of these states is , in general , also very specifically coupled to the vibrational degrees of freedom of the junction such that interaction of the tunneling electrons with the vibrations gives information about their tunneling pathway . this which - path information quenches the interference effects that are inherent to transport through quasidegenerate states . as we have shown , this decoherence mechanism is more pronounced for higher levels of vibrational excitation or , equivalently , higher effective temperatures of the vibrations , because the probability for an interaction of the tunneling electron with the vibrations increases with temperature . for example , at high bias voltages , where resonant transport processes may result in high levels of vibrational excitation , vibrationally induced decoherence is therefore very pronounced and quantum interference effects play only a minor role . at the onset of the resonant transport regime , however , interference effects may result in sizable effects , such as , for example , a reorganization of step heights in the current - voltage characteristics or a modification of the widths of these steps . at low bias voltages or in the non - resonant transport regime , where the excitation levels of the vibrational modes are typically rather low , vibrationally induced decoherence is less pronounced . in this regime , the interplay between interference and decoherence may , nevertheless , result in a strong modification of the signals that are associated with inelastic electron tunneling . for example , in the presence of destructive interference effects , the onset of inelastic processes is , in general , more pronounced , while in the presence of constructive interference effects the respective signals are suppressed or even reversed . as a result , negative jumps in the conductance - voltage characteristic can appear , although the conductance of the molecule is much smaller than the conductance quantum @xcite . a correct and thorough analysis of vibrational signals in the transport characteristics of a single - molecule contact needs to take into account these effects , as they may lead to strong deviations from the commonly employed franck - condon picture . we have also elucidated the role of electron - hole pair creation processes in the presence of strong destructive quantum interference effects . in contrast to transport processes , electron - hole pair creation processes are not suppressed by interference effects and , therefore , constitute the dominant inelastic processes in such junctions . at low temperatures of the electrodes , they are solely cooling the vibrational degrees of freedom . in this case , the effective temperature of the vibrational modes is only very weakly influenced by inelastic electron transport processes and rather determined by the temperature of the electrodes . because the level of vibrational excitation determines , inter alia , the efficiency of vibrationally induced decoherence in such a junction , electron - hole pair creation processes thus facilitate an effective mechanism to control quantum interference effects in single - molecule junctions by an external control parameter , that is the temperature of the electrodes . this has recently been demonstrated in experiments on a variety of different molecular junctions by ballmann _ et al . _ @xcite . while we have presented a comprehensive study of vibrationally induced decoherence in single - molecule junctions , further research is required that addresses not only the anti - adiabatic regime but also the adiabatic and the respective cross - over regime . as quantum interference effects appear in particular for quasi - degenerate electronic states , it is also interesting to investigate the effect of non - adiabatic electronic - vibrational coupling @xcite in these systems . moreover , the analysis should be extended to regimes , where the renormalized electron - electron interactions @xmath42 ( cf . [ hamiltonian ] ) are not negligible . these extensions require the development of theoretical methods that allow a nonperturbative description of electron - electron interactions as well as electronic - vibrational coupling , including higher order effects and correlations . we thank s. ballmann , s. brisker - klaiman , p. b. coto , b. kubala , a. nitzan , u. peskin and h. b. weber for many fruitful and inspiring discussions . mt gratefully acknowledges the hospitality of the ias at the hebrew university jerusalem within the workshop on molecular electronics . the generous allocation of computing time by the computing centers in erlangen ( rrze ) , munich ( lrz ) , and jlich ( jsc ) is gratefully acknowledged . this work has been supported by the german - israeli foundation for scientific development ( gif ) and the deutsche forschungsgemeinschaft ( dfg ) through the dfg - cluster of excellence engineering of advanced materials and sfb 953 . rh acknowledges support by the alexander von humboldt foundation . in this appendix , we derive the transmission function of model desvib and the corresponding incoherent and interference term ( cf . eqs . ( [ condesparts ] ) , sec . [ sequtunreg ] ) . to this end , we employ the wide - band approximation , @xmath115 , and consider large bias voltages ( @xmath116 ) . furthermore , we evaluate the vibrational degree of freedom in thermal equilibrium , that is we restrict it to an effective ( finite ) temperature @xmath117 . given these assumptions , the real - time projections of the corresponding electronic self - energy matrices ( [ elselfen ] ) can be written as @xmath118 with @xmath119 the retarded / advanced projection of the electronic part of the single - particle green s function ( cf . ( [ eldy ] ) ) is therefore given by @xmath120 and , according to the keldysh equations ( [ elke ] ) , we write the corresponding greater green s function as @xmath121 the greater projection of the single - particle green s function matrix ( see eq . ( [ decoupling ] ) ) thus reads @xmath122 with @xmath123 and @xmath124 the @xmath125th bessel function of the first kind . thereby , we have used the lesser projection of the shift operator correlation function @xcite @xmath126 \nonumber\\ & = & \delta_{m2 } \delta_{n2 } a^{2 } \sum_{l=-\infty}^{\infty } b_{l } \text{e}^{-i l \omega_{1 } ( t - t')},\end{aligned}\ ] ] and convoluted this function with the lesser projection of the electronic part of the single - particle green s function according to eq . ( [ decoupling ] ) . finally , the transmission function is obtained using the meir - wingreen - like formula ( [ currentformula ] ) , which can be rewritten as @xmath127 with @xmath128 for large bias voltages , this expression can be used to define a transmission function by @xmath129 \equiv 2e\int_{\infty}^{\infty}\frac{\text{d}\epsilon}{2\pi}\ , t(\epsilon ) . \end{aligned}\ ] ] this transmission function is given by @xmath130 \\ & = & \text{tr}\left [ \left ( \begin{array}{cc } i\gamma & i\gamma \\ i\gamma & i\gamma \\ \end{array } \right ) \left ( \begin{array}{cc } -i\gamma \vert g_{1}^{\text{r}}(\epsilon ) \vert^{2 } & i\gamma a^{2 } g_{1}^{\text{r}}(\epsilon ) g_{2}^{\text{a}}(\epsilon ) \\ i\gamma a^{2 } g_{2}^{\text{r}}(\epsilon ) g_{1}^{\text{a}}(\epsilon ) & -i\gamma a^{2 } \sum_{l=-\infty}^{\infty } b_{l } \vert g_{2}^{\text{r}}(\epsilon - l\omega_{1 } ) \vert^{2 } \\ \end{array } \right)\right ] \nonumber\\ & = & \gamma^{2 } \vert g_{1}^{\text{r}}(\epsilon ) \vert^{2 } - \gamma^{2 } a^{2 } \left ( g_{2}^{\text{r}}(\epsilon ) g_{1}^{\text{a}}(\epsilon ) + g_{1}^{\text{r}}(\epsilon ) g_{2}^{\text{a}}(\epsilon ) \right ) + \gamma^{2 } a^{2 } \sum_{l=-\infty}^{\infty } b_{l } \vert g_{2}^{\text{r}}(\epsilon - l\omega_{1 } ) \vert^{2}. \nonumber\end{aligned}\ ] ] the respective incoherent term is obtained by neglecting the off - diagonal elements of @xmath131 in eq . ( [ auxua ] ) ( cf . the discussion given in sec . [ basintsec ] ) @xmath132 which also allows to identify the corresponding interference term as @xmath133 in this appendix , we derive the transmission function of model convib and the corresponding incoherent and interference term ( cf . eqs . ( [ condespartsii ] ) , sec . [ sequtunreg ] ) . to this end , we employ the same approximations as in appendix [ transdesvib ] . the corresponding real - time projections of the electronic self - energy matrices ( [ elselfen ] ) are given by @xmath134 leading to the following retarded / advanced projection of the electronic part of the single - particle green s function ( cf . ( [ eldy ] ) ) : @xmath135 according to the keldysh equations ( [ elke ] ) , we can write the greater projection of the ( electronic ) green s function as @xmath136 with @xmath137 convolution of this expression with the greater projection of the shift operator correlation functions ( [ shiftopfunc ] ) leads , according to eq . ( [ decoupling ] ) , to the greater projection of the single - particle green s function matrix @xmath138 the corresponding transmission function , as defined by eq . ( [ deftrans ] ) , thus reads @xmath139 \\ & = & \gamma^{2 } \text{tr}\left [ \left ( \begin{array}{cc } 1 & 1 \\ 1 & 1 \\ \end{array } \right ) \left ( \begin{array}{cc } c(\epsilon ) z_{11}(\epsilon ) & a c(\epsilon ) z_{12}(\epsilon ) \\ a c(\epsilon ) z_{21}(\epsilon ) & a^{2 } \sum_{l=-\infty}^{\infty } b_{l } c(\epsilon - l\omega_{1 } ) z_{22}(\epsilon - l\omega_{1 } ) \\ \end{array } \right)\right ] \nonumber\\ & = & \gamma^{2 } \left ( c(\epsilon ) z_{11}(\epsilon ) + a c(\epsilon ) z_{21}(\epsilon ) + a c(\epsilon ) z_{12}(\epsilon ) + a^{2 } \sum_{l=-\infty}^{\infty } b_{l } c(\epsilon - l\omega_{1 } ) z_{22}(\epsilon - l\omega_{1 } ) \right ) . \nonumber\end{aligned}\ ] ] considering the contributions of the off - diagonal elements of @xmath131 in eq . ( [ auxua2 ] ) ( cf . the discussion given in sec . [ basintsec ] ) , it can be decomposed into the interference term @xmath140 and the incoherent term @xmath141
we investigate the interplay of quantum interference effects and electronic - vibrational coupling in electron transport through single - molecule junctions , employing a nonequilibrium green s function approach . our findings show that inelastic processes lead , in general , to a quenching of quantum interference effects . this quenching is more pronounced for increasing bias voltages and levels of vibrational excitation . as a result of this vibrationally induced decoherence , vibrational signatures in the transport characteristics of a molecular contact may strongly deviate from a simple franck - condon picture . this includes signatures in both the resonant and the non - resonant transport regime . moreover , it is shown that local cooling by electron - hole pair creation processes can influence the transport characteristics profoundly , giving rise to a significant temperature dependence of the electrical current .
WASHINGTON—It's hard to picture someone mindlessly ingesting three McDonald's Quarter Pounders with 12 pats of butter while watching a movie. But according to new laboratory analyses commissioned by the nonprofit Center for Science in the Public Interest, that food is nutritionally comparable to what you’d find in a medium popcorn and soda combo at Regal, the country’s biggest movie theater chain: 1,610 calories and three days’ worth—60 grams—of saturated fat. (Nutrition aside, that combo costs $12—for raw ingredients that must cost Regal pennies.) "Regal and AMC are our nominees for Best Supporting Actor in the Obesity Epidemic," said CSPI senior nutritionist Jayne Hurley. "Who expects about 1,500 calories and three days’ worth of heart-stopping fat in a popcorn and soda combo? That’s the saturated fat of a stick of butter and the calories of two sticks of butter. You might think you’re getting Bambi, but you’re really getting Godzilla." A medium combo at Regal has 1,610 calories and 60 grams of saturated fat. That's roughly the saturated fat of a stick of butter and the calories of two sticks of butter. Photo Credit: Stephen Schmidt Regal says that its medium popcorn has 720 calories and that its large has 960. But CSPI's lab tests found that those numbers were understated. Regal’s medium and large sizes each had 1,200 calories and, thanks to being popped in coconut oil, 60 grams of saturated fat. (The large size looks bigger, thanks to its titanic tub, but it costs a dollar more and comes with a free refill.) A "small" at Regal has 670 calories and 34 grams of saturated fat. That’s about as many calories as a Pizza Hut Personal Pan Pepperoni Pizza—except the popcorn has three times the saturated fat. Even shared with another person, that size provides nearly an entire day’s worth of the kind of fat that clogs arteries and promotes heart disease. And every tablespoon of "buttery" oil topping adds another 130 calories. Asking for topping is like asking for oil on French fries or potato chips, according to CSPI. AMC, the second largest theater chain, also pops in coconut oil but has smaller serving sizes. Its large popcorn has 1,030 calories and 57 grams of saturated fat. That's like eating a pound of baby back ribs topped with a scoop of Häagen-Dazs ice cream—except that the popcorn has an additional day’s worth of saturated fat. A medium has 590 calories and 33 grams of saturated fat; and a small has 370 calories and a day’s worth—20 grams—of saturated fat. (Like Regal, AMC reports calorie counts lower than those returned in CSPI's lab tests.) Third-largest Cinemark pops in heart-healthy canola oil. A large has 910 calories with 4 grams of saturated fat; a medium has 760 calories and 3 grams of saturated fat; and a small has 420 calories and 2 grams of saturated fat. Though popping in canola gives this chain’s popcorn far less saturated fat than its competitors, it's almost as high in calories and has the most sodium—about twice as much as Regal or AMC. With 1,500 milligrams of sodium—a day's worth of sodium for most people—a large popcorn without topping from Cinemark will be less likely to clog your arteries but more likely to elevate your blood pressure. And while Cinemark uses a "buttery" oil topping similar to the toppings used at Regal and AMC, at some outlets, particularly in the West, it uses a topping made with real butter. That version has 9 grams—half a day’s worth—of saturated fat per tablespoon. CSPI also took a look at the sodas and candies sold at the movies. A small non-diet soda ranges from 150 calories at Cinemark to 300 calories at Regal. Mediums have 300 calories at AMC and Cinemark and 400 calories at Regal. With 33 teaspoons of sugar in nearly 2 quarts—54 ounces—Regal has the most outsized large soda, with 500 empty calories. Eating an 8-ounce bag of Reese's Pieces is like eating a 16-ounce T-bone steak and a buttered baked potato. Photo Credit: Stephen Schmidt The oversized boxes and bags (four to five ounces) of candy sold at movie chains are universally high in calories. A 5-ounce bag of Twizzlers has 460 calories and 15 teaspoons of sugar. A 7-ounce box of Nerds has 790 calories and 46 teaspoons of sugar. Chocolate candies like Butterfinger Minis, Raisinets, Sno-Caps, or M&M's have between 400 and 500 calories and at least a half day’s worth of saturated fat. An 8-ounce bag of Reese's Pieces is just a cup of candy. But with 1,160 calories and 35 grams of saturated fat, it's like eating a 16-ounce T-bone steak plus a buttered baked potato. "Sitting through a two-hour movie isn't exactly like climbing Mt. Everest," Hurley said. "Why do theaters think they need to feed us like it is?" The study, published as the cover story in the December issue of Nutrition Action Healthletter, updates a famous exposé the group conducted 15 years ago. For Regal and AMC, CSPI tested samples from theaters in the Washington, D.C., area. For Cinemark, samples came from Texas, Illinois, and Maryland. ||||| A medium-sized popcorn and medium soda at the nation's largest movie chain pack the nutritional equivalent of three Quarter Pounders topped with 12 pats of butter, according to a report released today by the advocacy group Center for Science in the Public Interest.The group's second look at movie theater concessions -- the last was 15 years ago -- found little had changed in a decade and a half, despite theaters' attempts to reformulate.CSPI bought multiple servings of popcorn from the three largest movie chains, Regal Entertainment Group, AMC and Cinemark, and had them analyzed in an independent lab.It found that a Regal medium popcorn -- 20 cups -- contains 1,200 calories, 60 grams of saturated fat, and 980 milligrams of sodium. That's without the buttery topping that can be drizzled -- or poured -- on the popcorn, which adds another 200 calories and 3 grams of saturated fat per 1.5 tablespoons.An AMC medium popcorn did better because of its smaller size -- nine cups -- at 590 calories and 33 grams of saturated fat, and a 14-cup Cinemark medium was 760 calories and just 3 grams of saturated fat (in both cases, before adding buttery topping).One problem is that Regal and AMC, the two largest chains, pop their popcorn in coconut oil, which is about 90% saturated fat, noted Jayne Hurley, senior nutritionist at Washington-based CSPI.Cinemark, the third-largest chain, now pops its corn in canola oil, which explains its much lower saturated fat levels."Cinemark gets a thumbs-up for switching," Hurley said.In two positive steps, trans fatty acids were not found in the samples, Hurley added, and theaters have stopped using hydrogenated oils in the butter-flavored toppings.The study, published in the December issue of CSPI's Nutrition Action HealthLetter, found that in several cases the theater company calorie counts were lower than the numbers revealed in the study.For example, Regal's figure of 720 calories for a medium popcorn was considerably lower than the one determined by CSPI. (The company declined to comment beyond a general statement.)Several chains either did not respond to requests for comment or said they would have no comment. Regal, in its statement, said that movie popcorn is not meant to be daily fare and that it acknowledges some of the food it sells is healthier than others."According to the most recent statistics from the Motion Picture Assn. of America, the average American attends six movies a year," Regal said. "Theater popcorn and movie snacks are viewed as a treat and not intended to be part of a regular diet."It's unclear if consumers would storm the concession stand for low-cal popcorn anyway. After the 1994 popcorn report, "many cinema operators responded by offering their patrons additional choices, such as air-popped popcorn," the National Assn. of Theatre Owners said in a statement."After very little time, movie patrons in droves made their voices heard -- they wanted the traditional popcorn back."
– Figure 1,600 calories, 60 grams of saturated fat, and 980 milligrams of sodium—that’s what you’re eating when you scarf down a medium helping of movie popcorn at the nation's biggest theater chain. Add a soda and it’s the equivalent of eating a pound of baby back ribs and a scoop of ice cream, or three Quarter Pounders with a stick and a half of butter, an analysis by a nutrition watchdog group says. In many cases, calorie counts are significantly higher than those posted in theaters. Regal, the No. 1 chain, and AMC cook their popcorn in coconut oil, which is 90% saturated fat, while Cinemark gets better grades—relatively speaking—for using canola oil, reports the LA Times.
the thalassemias are a group of hemoglobinopathies characterized by a deficient synthesis of protein chains ( either or the ) of globin in the hemoglobin molecule . affected individuals are either heterozygotes , homozygotes , or compound heterozygotes for the - or -chain genes . the heterozygous individual are known as having the - or -thalassemia trait which is the milder form ; the homozygous state is known as a - thalassemia or -thalassemia major ( cooley 's anemia ) which presents with severe manifestations of the disease . the condition was first described by thomas cooley and pearl lee detroit in 1925 . in b thalassemia major , the production of beta globin chains is severely impaired as mutation occurs in the sequence of beta globin gene which results in a severe or total suppression of beta chain synthesis . the patient has anemia and the red blood cells ( rbcs ) show microcytic and hypochromic appearance with an aberrant morphology . this hypertransfusion treatment results in iron overload which is life - limiting complication commonly found in thalassemia patients . it is mainly because of ineffective erythropoiesis and increased absorption of iron in gastrointestinal tract , lack of physiologic mechanism for excreting excess iron , and above all multiple blood transfusions . a unit of packed rbcs contains 250300 mg iron ( 1 mg / ml ) , so that a single transfusion of two units of packed rbcs is about equal to a 12 year intake of iron . the signs of a clinical toxicity become apparent , when the body iron concentration reaches 4001000 mg / kg of the body weight . iron overload occurring due to repeated blood transfusion leads to excessive parenchymal accumulation of this element , causing multiorgan failure and death subsequently . body iron status can be evaluated by assessing serum ferritin level for the diagnosis of iron overload and monitoring the response to treatment . however , serum iron concentration is increased in some diseases even when the body iron stores are within normal limits , as in acute and chronic liver damage , malignancies , infections , and megaloblastic anemia . a liver and bone marrow biopsy is , therefore , required to accurately identify iron overload in parenchymal cells , but these procedures are invasive and , therefore , are not advisable in each case . the present study was designed to assess the utility of perl 's prussian blue in the exfoliated buccal epithelial cells assess the iron overload and its correlation with serum ferritin levels in beta - thalassemia patients undergoing repeated blood transfusions . the present study comprised 35 -thalassemia major patients in the age group of 528 years undergoing repeated blood transfusions and 10 systemically healthy patients in the control group . patients with iron deficiency anemia , megaloblastic anemia , hepatitis , malignancy , and chronic liver damage were excluded from the study . the study subjects were regularly taking oral iron - chelation therapy for more than 1 year . the buccal mucosa of the patients were scraped with a wet wooden spatula after rinsing their mouth with distilled water and smeared onto a glass slide . the smear was fixed immediately in 70% ethanol for 1 h and then stained with perl 's prussian blue . the stained smears were examined under the research microscope ( olympus b 41 ) to study the presence or absence of blue colored intracytoplasmic granules in the oral epithelial cells . the iron overload was assessed using serum ferritin levels of the patients at the time of taking the oral cytosmears . the study group included 21 males ( 60% ) and 14 females ( 40% ) and the mean age was 16.07 6.57 years . the positive cytological smears showed blue colored granules in the cytoplasm of exfoliated oral epithelial cells stained with perl 's prussian blue stain [ figures 1 and 2 ] . twenty - nine ( 82.9% ) cases showed positive reaction for perl 's prussian blue reaction while 6 ( 17.1% ) cases did not show the presence of blue colored granules in the oral cytosmears . the presence of iron by perl 's prussian blue staining reaction was correlated with serum ferritin level and a statistically significant difference ( t - test , p < 0.05 ) was observed for the presence of high iron overload and its detection through perl 's prussian blue in exfoliative cytology [ table 1 ] . however , the results did not correlate statistically with gender of the patients thus indicating that the findings were not related to gender in the study group [ table 2 ] . the number of cases with exfoliative cytosmears showing reaction with perl 's prussian blue correlated with the increasing levels of serum ferritin levels in these patients [ figure 3 ] . photomicrograph showing blue colored intracytoplasmic granules in the exfoliated oral epithelial cells ( perl 's prussian blue , 40 ) photomicrograph showing positive staining for iron in the cytosmears ( perl 's prussian blue , 40 ) correlation of the presence of iron in exfoliated oral epithelial cells with serum ferritin levels in patients with beta - thalassemia correlation of prussian blue reaction with gender in the study group correlation of serum ferritin levels with positivity of oral cytosmears with perl 's prussian blue reaction beta - thalassemia is characterized by increased serum iron levels due to combined effects of increased ferritin synthesis and the release of intracellular ferritin from damaged cells . iron stores in the body show variation depending mainly on the intensity of transfusion and the efficacy of chelation . iron overload can also be seen in various conditions such as hereditary hemochromatosis , thalassemia major , aplastic anemia , and myelodysplasia due to the lack of specific excretory pathways . chemical quantification of iron in liver biopsy tissue has been considered the gold - standard for assessing body iron stores . highlighted the limitations of a single biopsy in predicting long - term complications of transfusional iron overload . oral exfoliative cytology is a simple and noninvasive procedure which can be used to study the cytological and nuclear features in exfoliated oral epithelial cells . the cytosmears were used to assess the iron overload by using perl 's prussian blue staining reaction by histochemical demonstration of iron in the cytoplasm of the oral epithelial cells . perl 's prussian blue reaction is based on the principle that acidified potassium ferrocyanide solution binds to iron in tissue , forming a relatively insoluble blue - purple precipitate . in the present study , 82.9% cases showed positivity for perl 's prussian blue staining reaction in the cytological smears of exfoliated buccal cells . our findings were similar to those observed by nandaprasad et al . who observed 65% , bhat et al . who found ( 71.7% ) , gupta et al . who found 61.6% positivity , and gururaj and sivapathasundaram ( 2003 ) who observed 100% positivity . the presence or absence of these granules is not age or gender specific as previously shown by nandaprasad et al . based on the results of our study , it can be stated that perl 's prussian blue reaction can be utilized as an objective indicator of iron overload in beta - thalassemic patients with high levels of iron overload .
background : increased iron overload is frequent problem in thalassemia patients , and this is monitored by serum ferritin levels or chemical assessment of the iron levels in liver tissue . however , repeated monitoring of serum ferritin levels to assess the iron overload is an invasive procedure associated with practical problems.aims:to use perl 's prussian blue reaction to evaluate the iron overload in beta - thalassemia patients by staining the oral cytosmears.materials and methods : the study comprised 35 patients diagnosed with beta - thalassemia . cytosmears were prepared from exfoliated oral epithelial cells , fixed in 70% ethanol and stained with perl 's prussian blue stain for detection of blue colored granules in the cytoplasm.results:29/35 ( 82.9% ) cases showed a positive reaction for perl 's prussian blue reaction while 6/35 ( 17% ) cases did not show the presence of blue colored granules in the oral cytosmears . the presence of iron detected by perl 's prussian blue reaction correlated with serum ferritin level ( p < 0.05).conclusion : perl 's prussian blue reaction can be used to evaluate the iron overload in beta - thalassemia patients by staining the oral cytosmears . it is a simple and noninvasive method for assessment of iron overload in such patients .
the development of resistance is a major clinical problem with current anticancer drugs . multitargeting by using a combination of drugs provides a potential strategy to overcome resistance . we are exploring the concept of redox synergism for combination therapy , a strategy that could additionally lower the doses of metallodrugs . metal complexes based on ru(ii ) , os(ii ) , and ir(iii ) are being developed as viable alternatives to platinum drugs used in the clinic . metal - based anticancer drugs can interfere in cellular redox chemistry in several ways : directly through metal or ligand redox centers , or indirectly by binding to biomolecules involved in cellular redox pathways . this opens the possibility to target the redox balance in cancer cells , which may be a highly effective , multiple site approach . in the present work , we show that combining metal - based drugs and redox modulators not only improves potency but also has great repercussions for the selectivity of the complex toward cancer cells . conventional platinum drugs target dna and therefore rely on the high proliferation rate of cancer cells as a basis for selectivity . in contrast , organometallic osmium(ii ) complexes , such as fy26 , [ os(-p - cym)(p - nme2-azpy)i]pf6 ( figure 1a ) , have a novel mechanism of action centered on increasing the level of reactive oxygen species ( ros ) produced in cancer cells . cancer cells are primed for this intervention because they are already redox - hyperactive and in most cases present malfunctioning mitochondria . several factors are known to contribute to mitochondrial dysfunction in cancer cells , including mtdna mutations , oncogenic stress , and p53 mutations . functional mitochondria are responsible for a plethora of cellular processes , including atp production , ros generation , and cell death . dysfunctional mitochondria are unable to control ros generation efficiently , leading to inherent oxidative stress in cancer cells . this allows osmium compounds , such as fy26 , to exert selective toxicity toward cancer cells over normal cells . ( a ) chemical structure of fy26 , ( b ) antiproliferative activity of fy26 5 m l - bso in a2780 ovarian cancer cells ( orange ) and mrc5 human lung fibroblasts ( white ) . the selectivity factor ( ic50-mrc5/ic50-a2780 ) increases from 28.4 to 63.5. multicomponent therapy , in which the drugs used are synergistic , can provide dose reduction and subsequent minimization of adverse side effects while avoiding the development of resistance . some examples of conventional combination therapy for cancer include the use of aphidicolin glycinate and cisplatin ( cddp ) in the treatment of melanomas and paclitaxel combined with carboplatin for ovarian and nscl cancers . we have shown that a number of active organometallic anticancer agents based on ru(ii ) , os(ii ) , and ir(iii ) have potential redox components in their mechanisms of action . for such complexes , the possibility arises of using combination therapy together with redox modulators to increase their potency . this is attractive for lowering the doses of metal complexes that need to be administered . osmium complex fy26 is highly active toward several cancer cell lines , in particular , it exhibits submicromolar activity in a2780 ovarian , a549 lung , hct116 colon , and mcf7 breast cancer cell lines . fy26 is more potent than cisplatin by at least 2 orders of magnitude in the nci-60 cell line screen ( gi50 fy26 0.28 m versus 10.3 m for cddp ) as well as in the 809-cell line screen of the sanger institute ( mean gi50 fy26 0.75 m versus 36.7 m for cddp ) . we have further investigated the anticancer activity and mechanism of action on fy26 toward ovarian cancer , using a2780 cells as a model . current statistics , held by cr - uk , indicate that we lose one woman every 2 h due to this disease . importantly , we have reported that the activity of fy26 can be potentiated by coadministration of a nontoxic dose of the redox modulator l - buthionine sulfoximine , l - bso , an inhibitor of -glutamylcysteine synthetase . this effect has also been observed for piano - stool complexes based on ru(ii ) and ir(iii ) . in the case of the activity of fy26 toward a2780 ovarian cancer cells , potency improves by 2.3-fold when coadministered with 5 m of l - bso , with the ic50 decreasing from 160 10 nm to 69 5 nm . in the present work , we show that combination of fy26 with nontoxic doses of l - bso dramatically increases the selectivity of the os complex for cancer cells over normal fibroblasts . we describe a series of experiments in which we investigated the effect of low , nontoxic doses of the redox modulator l - buthionine sulfoximine , l - bso , an inhibitor of the enzyme -glutamyl cysteine synthetase that catalyzes the first and rate - limiting step in the production of glutathione ( gsh ) . this redox modulator has been in clinical trials for malignant melanoma ( nci - t93 - 0176o ) and refractory progressive neuroblastoma ( nct00002730 ) in combination with melphalan . the results so far indicate that it can be safely used to generate a 40% gsh depletion in patients . in the present work , l - bso has been used in combination with the organo - os(ii ) complex fy26 in studies on the antiproliferative activity in a2780 ovarian cancer cells and mrc5 human fibroblasts , effects on gsh levels , on the induction of ros and superoxide , the involvement of apoptosis in cell death , and on mitochondrial membrane potentials and cell - cycle profiles . the antiproliferative activity of fy26 has previously been reported in the a2780 ovarian cell line ( ic50 = 160 nm ) as well as the possibility of enhancing its activity by coadministration with 5 m l - bso . we have investigated whether this potentiation of anticancer activity is also observed for inactive os(ii ) piano - stool complexes . for this , we determined the ic50 of fy77 ( [ os(-bip)(cl - azpy)cl]pf6 ic50 > 100 m ) and fy122 ( [ os(-p - cym ) ( oh - impy)i]pf6 ic50 = 30 2 m ) which are structurally related organometallic complexes but have much lower potencies than fy26 . we then determined the percentages of cell survival when different concentrations of fy77 and fy122 are coadministered with 5 m of l - bso ( supporting information ( si ) figure 1 ) . the biphenyl complex fy77 remains inactive , with percentages of cell survival above 93% . this indicates that l - bso does not confer antiproliferative activity per se and can only enhance the performance of a complex that is already biologically active . we hypothesized that the cellular effect of l - bso in reducing gsh levels is directly related to the enhancement of antiproliferative activity . to confirm this , we investigated whether the effect of coincubation with l - bso could be reversed by also coadministering gsh . a2780 ovarian cancer cells exposed to a fixed concentration of fy26 ( 0.10 or 0.30 m ) were coincubated with ( a ) 5 m l - bso , ( b ) 5 m gsh , ( c ) 5 m l - bso and 5 m gsh , ( d ) 50 m gsh , or ( e ) 5 m l - bso and 50 m gsh ( figure 2 and si figure 2 ) . effect of coadministration of 0.10 m fy26 with 5 m l - bso in the presence / absence of gsh ( 5 and 50 m ) on the percentage of cell survival of a2780 ovarian cancer cells . the administration of 0.10 m of fy26 and 5 m l - bso , as expected , reduced the percentage of cell survival compared to the administration of the complex on its own . this effect was partially reversed in the presence of gsh as well as l - bso ( figure 2 ) . in fact , when cells were coincubated with only fy26 and gsh , the percentage of cell survival increased in comparison to the osmium drug alone . this suggests that the effect of l - bso may be related to modulating the cellular response to the osmium drug . more specifically , the role of l - bso is to reduce the level of gsh as a cellular detoxification agent . the anticancer activity of metal - based drugs may well involve both cytostatic and cytotoxic effects . to investigate the contribution of these two effects , the percentages of survival of cells exposed to the drug when allowed or not allowed to recover in drug free medium were compared . we carried out this experiment on a2780 ovarian cancer cells exposed for 24 h to various concentrations of fy26 . these values were then compared to cells that were drug - exposed under similar conditions but were then allowed to recover for further 72h in drug - free medium ( si figure 3a ) . at concentrations between 75 and 0.3 m fy26 the percentage of cell survival was always significantly lower for cells that were allowed to recover , which highlights the cytostatic effect of fy26 . meanwhile at the lowest concentration tested ( 30 nm ) , no differences were observed and the percentage of cell survival was very similar to that of untreated controls . we also determined the percentages of cell survival when a2780 cells were exposed to 5 m l - bso in coadministration with various concentrations of fy26 ( si figure 3b ) . the use of the redox modulator did not change the trends observed , and once more the percentage of cells in the experiment that included 72 h recovery in drug - free medium was lower . this suggests that in the presence and absence of l - bso the behavior of fy26 is mostly cytostatic . the selectivity factor for a given compound can be defined as the ratio between its activity ( ic50 ) in normal cells ( mrc5 fibroblasts in the present case ) compared to cancer cells . the selectivity of fy26 ( ic50-mrc5/ic50-a2780 ) is 28 , while the corresponding factor for cddp is only 9.5 . we studied the effect on the selectivity factor of combined administration of a 5 m nontoxic dose of l - bso together with fy26 to a2780 human ovarian cancer cells compared to mrc5 fibroblasts . remarkably , the selectivity factor increased to 63.5 ( figure 1b , si table 1 ) . the activity in the fibroblasts remains unchanged , but the potency in the ovarian cancer cells increases . such a differential activity might allow the use of combination therapy for dose reduction and translate into reduction of unwanted side effects . we investigated the effect of l - bso on the gsh levels in a2780 ovarian cancer cells . we treated a2780 cells with three different concentrations of l - bso : 1 , 5 , and 50 m . compared to untreated controls , 1 m l - bso treatment did not cause significant variations in the gsh levels ( to 95% ) , but 5 m l - bso induced an approximate 50% drop ( to 56% ) , and the highest concentration ( 50 m ) caused a 63% reduction ( to 37% ; figure 3a , si table 2 ) . gsh levels in a2780 cells exposed for 24 h to ( a ) l - bso ( 1 , 5 , and 50 m ) , ( b ) fy26 ( ic50 and 2 ic50 ) 5 m l - bso . in all cases , we chose 5 m l - bso to carry out experiments on coadministration with fy26 . in this case , the levels of gsh were reduced , as expected , to ca . the variation caused by a single dose of fy26 at ic50 concentration was a decrease to 92% . at 2 ic50 concentration , it is possible that at high concentrations of the complex , gsh is used as a cellular strategy for drug detoxification ( figure 3b , si table 2 ) . this effect has been observed before , for example , reduced levels of gsh ( caused by l - bso administration ) can restore cellular sensitivity to the ru(iii ) anticancer drug kp1019 . we then determined the induction of ros and superoxide in a2780 ovarian cancer cells exposed for 24 h to complex fy26 at the ic50 concentration ( 160 nm ) using flow cytometry and compared this to the ros and superoxide levels observed in mrc5 fibroblasts under similar conditions . the experiment allowed the simultaneous determination of total oxidative stress ( e.g. , peroxides , peroxynitrite , and hydroxyl radicals ) using the fl-1 green channel and the generation of superoxide using fl-2 orange channel . ovarian cancer cells exposed to fy26 showed high levels of both total ros and superoxide , with most of the cell population in the fl-1+/fl-2 + upper right quadrant of a dot plot . meanwhile , untreated negative controls remained in the lower left quadrant , with low levels in both channels ( figure 4a , b , si table 3 ) . in contrast , mrc5 fibroblasts exposed to fy26 exhibited elevated levels of total ros but showed low induction of superoxide , with most of the population in the lower half of the fl-2 orange channel ( figure 4c ) . flow cytometry analysis of the induction of total ros and superoxide : ( a ) positive and negative controls in a2780 ovarian cancer cells , ( b ) fy26 ( ic50 ) 5 m l - bso in a2780 cells , and ( c ) mrc5 normal fibroblasts exposed to fy26 ( ic50 ) . in all cases , these observations are consistent with the proposed mechanism of action for fy26 , which is based on the disruption of the cellular redox balance . we hypothesize that fy26 exerts its anticancer activity by generating a burst of superoxide , hence exploiting the weaknesses of defective mitochondria in cancer cells . the mrc5 fibroblasts which contain normal functioning mitochondria are capable of rebalancing the redox state of the cell efficiently , while the a2780 progress toward cell death . a similar experiment was carried out using a combination of fy26 and 5 m of l - bso in a2780 ovarian cancer cells . both of these readings remained unchanged compared to the administration of the osmium complex alone , showing the majority of the cell population in the upper right quadrant fl-1+/fl-2 + ( figure 4b si table 4 ) . remarkably , no further increase in the levels of superoxide is observed in the presence of fy26 and l - bso , which indicates that the enhancement in anticancer activity is the result of a weakened cell response to the osmium complex due to the lower gsh levels . as a second set of negative controls ( apart from the untreated cells ) , a2780 cells exposed to 5 m of l - bso showed only population in the fl-1/fl-2 lower left quadrant , indicating low levels of both superoxide and total ros . we have reported that the levels of superoxide induction in a2780 ovarian cancer cells can be directly related to the antiproliferative activity of os(ii ) piano - stool complexes , in particular to the activity of fy26 , fy77 , and fy122 . there is no production of superoxide in cells exposed the inactive complex fy77 , and no improvement in anticancer activity when the complex is coadministered with 5 m l - bso . this is consistent with the idea that l - bso can only enhance the potency of already active complexes , such as fy26 , and that it does so by lowering gsh levels , hence weakening the cellular response to the osmium - complex . we have previously reported that ic50 concentrations of fy26 do not cause significant apoptosis in a2780 ovarian cancer cells after 24 h of drug exposure . under these conditions , the majority of the cell population in a flow cytometry dot plot remains in the lower left quadrant with fl-1 measuring annexin v fluorescence intensity and fl-2 reading propidium iodide fluorescence . apoptosis , as programmed cell death , starts with the loss of symmetry of the phosphatidylserine membrane , which allows annexin binding ( early apoptosis ) , followed by loss of the membrane integrity . at this point , cells become permeant to propidium iodide and generate high fluorescence in the fl-2 channel after dna intercalation ( late apoptosis ) . fy26 has been shown to cause apoptotic cell death in a549 lung cancer cells only at concentrations 10 ic50 , nonetheless at a dose of 0.5 m the apoptotic population can still be disregarded . we exposed a2780 ovarian cancer cells to fy26 under similar conditions ( 24 h drug exposure at ic50 concentration ) , this time coadministered with 5 m l - bso with the aim of determining whether the use of the redox modulator would induce higher levels of programmed cell death . figure 5a ( si table 5 ) shows that combination with the redox modulator does not cause significant changes to the apoptotic response . most of the cell population showed only low levels of annexin binding and propidium iodide intercalation , hence they are located in the fl-1/fl-2 lower left quadrant of the dot plot . there are , nonetheless , a statistically relevant ( p < 0.001 ) number of nonviable cells located in the upper left quadrant fl-1/fl-2 + , which only exhibit high propidium iodide fluorescence ; this is consistent with a nonapoptotic mechanism of cell death . the experiment was also carried out using a single dose of 5 m l - bso as a second set of negative controls . there were no statistically significant differences between the cells exposed to the redox modulator and the untreated controls , as all the population remained in the lower left quadrant , with low annexin v and low propidium iodide fluorescence . ( ic50 ) 5 m l - bso : ( a ) induction of apoptosis , ( b ) changes in the mitochondrial membrane potential , and ( c ) cell cycle analysis . a nonapoptotic mechanism of cell death does not rule out the involvement of mitochondrial dysfunction or redox disruption . in fact , it has been reported that pathogenic mitochondrial oxidation and even autophagic cell death can be linked to cellular redox disruption . there is also a need to consider that the mechanism of cell death caused by this type of multitargeted metal - based complex may be novel and difficult to map onto known mechanisms . we also investigated changes in the mitochondrial membrane potential of a2780 cells exposed to fy26 5 m l - bso using flow cytometry . first , we used the os(ii ) complex on its own , with a drug exposure of 24 h at ic50 ( 160 nm ) concentration . the experiment relies on the jc-10 mitochondrial stain which exists as a red aggregate inside the mitochondria , however , upon changes in the membrane potential , the dye is released into the cytosol and converted into its monomeric green form . following the increase of intensity in the fl-1 green channel , it is possible to quantify the release of the stain and hence gain information on changes in the mitochondrial membrane potential . a fl-1 histogram revealed that fy26 is capable of changing the potential of the mitochondrial membrane as indicated by a gain in the fluorescence intensity . similarly , we carried out the experiment with coadministration with 5 m l - bso . this combination did not affect markedly the results of this experiment , and changes in the mitochondrial membrane potential were still observed ( figure 5b , si table 6 ) . cell cycle profiles of a2780 cells exposed for 24 h to fy26 at ic50 concentration ( 160 nm ) 5 m l - bso were obtained by flow cytometry using propidium iodide as a dna stain . in both cases , with and without the redox modulator , it was observed that after the drug exposure period and no recovery time , a2780 cells were arrested in g1 phase and there was no significant population in a sub - g1 phase ( figure 5c ) . these results highlight the cytostatic effect of the os(ii ) complex and are consistent with the above studies of apoptosis in which 24 h of drug exposure does not lead to a majority population of nonviable cells . it is also consistent with the results obtained when cells exposed to fy26 are allowed or not to recover in drug - free medium before determining the percentages of cell survival ( vide supra ) . it is well - known that l - bso can deplete gsh levels in cells by inhibiting the enzyme -glutamylcysteine synthetase . furthermore , several previous studies have related intracellular levels of gsh with resistance to metal - based anticancer agents . gsh adducts can be recognized by atp - mediated efflux transporters and mdr proteins , which translates into reduced cell accumulation of the drugs . fy26 , a potent os(ii ) anticancer drug candidate , exerts its activity by generating reactive oxygen species and disrupting the redox balance in cancer cells . we have shown here that coadministration of fy26 and nontoxic doses of l - bso allows the potentiation of its anticancer activity , and most remarkably , it improves the selectivity for cancer cells versus normal fibroblasts . reduced gsh levels ( caused by the l - bso ) not only undermine cellular detoxification pathways but most importantly diminish the cell s ability to respond to oxidative stress . co - administration of fy26 with the redox modulator l - bso does not alter the levels of ros / superoxide produced in the cancer cells nor does it enhance the effect of the os(ii ) complex on the mitochondrial membrane potential . however , such a combination plays a key role in the cellular response to this damage . the vulnerability of the former arises from elevated energy requirements and the presence of dysfunctional mitochondria , while in the latter , balancing mechanisms are effective and redox variations , such as those induced by fy26 , are readily reversed . most notably , and in contrast to the cancer cells , treatment of normal fibroblasts with fy26 does not induce high levels of superoxide ( figure 4 ) . because metal - based drugs are often multitargeted , a systems pharmacology approach which considers their effects on feedback loops from interlinked pathways is likely to be beneficial for understanding their mechanisms of action and improving their design . smart and synergic combinations can be exploited to maximize the selectivity of metal - based anticancer drug candidates . the increase in selectivity of fy26 to a 63-fold difference between mrc5 fibroblasts and a2780 ovarian cancer cells is quite dramatic and would have a significant impact on therapeutic regimes if it could be translated into clinical practice . organometallic os(ii ) complexes fy26 , fy77 , and fy122 were synthesized and characterized as reported previously . staurosporine , propidium iodide ( 94% ) rnase a , pyocyanin and carbonyl cyanide 3-chlorophenylhydrazone , cccp , l - bso , and gsh were purchased from sigma - aldrich . a2780 human ovarian carcinoma and mrc5 human fetal lung fibroblasts were obtained from the european collection of cell cultures ( ecacc ) and grown in roswell park memorial institute medium ( rpmi-1640 ) , supplemented with 10% of fetal calf serum , 1% of 2 mm glutamine , and 1% penicillin / streptomycin . all cells were grown as adherent monolayers at 310 k in a 5% co2 humidified atmosphere and passaged at approximately 7080% confluency . briefly , 96-well plates were used to seed 5000 cells per well . the plates were left to preincubate in drug - free media at 310 k for 48 h before adding different concentrations of the compounds to be tested . a drug exposure period of 24 h was allowed . after this , supernatants were removed by suction and each well was washed with pbs . a further 72 h was allowed for the cells to recover in drug - free medium at 310 k. the srb assay was used to determine cell viability . ic50 values , as the concentration which caused 50% of cell death , were determined as duplicates of triplicates in two independent sets of experiments and their standard deviations were calculated . cddp - exposed and untreated cells were used as positive and negative controls , respectively . these experiments were performed using the protocol previously described for ic50 determination with the following modifications . cells were preincubated in drug - free medium for 48 h at 310 k before adding the metal complex fy26 together with 5 m l - bso . to prepare the stock solution of the drug , the solid complex was dissolved first in dmso and then diluted in a 50:50 v / v mixture of cell culture medium : saline ( 0.9% w / v nacl in sterile water ) to a maximum dmso concentration of 5% v / v . separately , a stock solution of l - bso was prepared in saline . both solutions , fy26 and l - bso , were added to each well independently but within 5 min of each other . drug exposure and recovery time were 24 and 72 h , respectively . these experiments used cells treated with different concentrations of cddp as positive controls and two sets of negative controls ; in the first one , the cells were kept untreated , while in the second set , the cells were exposed to 5 m l - bso . the differences in cell survival between the two sets of negative controls were not statistically significant in any experiment . a similar protocol was used to investigate the effect of coadministration with gsh . a2780 cells were drugged using fixed concentrations of fy26 ( 0.10 and 0.30 m ) and 5 m l - bso in the presence / absence of 5 and 50 m gsh . drug exposure and recovery time were 24 and 72 h , respectively . cells were seeded in a 6-well plate using 1.0 10 cells per well . they were preincubated in drug - free media at 310 k for 24 h , after which fy26 5 m l - bso were added using equipotent concentrations equal to ic50 and 2 ic50 for the os(ii ) complex . after 24 h of drug exposure , supernatants were removed by suction and cells were washed with pbs . dna staining was achieved by resuspending the cell pellets in pbs containing propidium iodide ( pi ) and rnase a. cell pellets were resuspended in pbs before being analyzed by flow cytometry using the maximum excitation of pi - bound dna at 536 nm and its emission at 617 nm . these experiments used two sets of negative controls , a first one using untreated cells and a second one with cells treated only with 5 m l - bso . these experiments were carried out in duplicates of triplicates in independent experiments ; although only selected dot plots are shown , full numerical data and statistical analysis can be found in the supporting information . flow cytometry analysis of apoptotic populations were carried out using the annexin v - fitc apoptosis detection kit ( sigma - aldrich ) according to the manufacturer s instructions . briefly , cells were seeded in 6-well plates ( 1.0 10 cells per well ) , preincubated for 24 h in drug - free media at 310 k , after which they were exposed to fy26 5 m l - bso for further 24 h ( equipotent concentrations of fy26 equal to ic50 and 2 ic50 ) . cells were harvested using trypsin and stained using pi / annexin v - fitc . after staining in the dark , cell pellets were analyzed in a becton dickinson facscan flow cytometer . for positive - apoptosis controls , a2780 cells were exposed for 2 h to staurosporine ( 1 g / ml ) . cells for apoptosis studies were used with no previous fixing procedure so as to avoid nonspecific binding of the annexin v - fitc conjugate . negative controls included untreated cells and cells treated only with 5 m l - bso . these experiments were carried out in duplicates of triplicates in independent experiments ; although only selected dot plots are shown , full numerical data and statistical analysis can be found in the supporting information . flow cytometry analysis of ros / superoxide generation by exposure to fy26 5 m l - bso was carried out using the total ros / superoxide detection kit ( enzo life sciences ) according to the supplier s instructions . briefly , 1.0 10 cells per well were seeded in a 6-well plate . cells were preincubated in drug - free media at 310 k for 24 h in a 5% co2 humidified atmosphere , and then drugs were added at equipotent concentrations equal to ic50 and 2 ic50 of fy26 and 5 m l - bso . after 24 h of drug exposure , supernatants were removed by suction and cells were washed and harvested . staining was achieved in the dark by resuspending the cell pellets in buffer containing the orange / green fluorescent reagents . cells were analyzed in a becton dickinson facscan flow cytometer using ex / em 490/525 nm for the oxidative stress and ex / em 550/620 nm for superoxide detection . negative controls included untreated cells and cells treated only with 5 m l - bso . these experiments were carried out as duplicates of triplicates in independent experiments ; although only selected dot plots are shown , full numerical data and statistical analysis can be found in the supporting information . analysis of the changes of mitochondrial potential was carried out using the abcam , jc-10 mitochondrial membrane potential assay kit according to the manufacturer s instructions . briefly , 1.0 10 cells were seeded in 6-well plates and left to incubate for 24 h in drug - free medium at 310 k in a humidified atmosphere . solutions of fy26 at ic50 and 2 ic50 concentrations 5 m l - bso were added in triplicate and the cells left to incubate for further 24 h under similar conditions . supernatants were removed by suction , and each well was washed with pbs before detaching the cells using trypsin - edta . staining of the samples was done in flow cytometry tubes protected from light , incubating 30 min at room temperature . negative controls included untreated cells and cells treated only with 5 m l - bso . these experiments were carried out as duplicates of triplicates in independent experiments ; although only selected dot plots are shown , full numerical data and statistical analysis can be found in the supporting information . gsh levels in cells exposed to fy26 l - bso were determined using the glutathione ( gsh / gssg / total ) assay kit from biovision according to the manufacturer s instructions . briefly , 1.0 10 cells were seeded in 6-well plates and left to incubate for 24 h in drug - free medium at 310 k in a humidified atmosphere . drug solutions of fy26 at ic50 and 2 ic50 concentration 5 m l - bso were added in triplicate and the cells left to incubate for further 24 h under similar conditions . supernatants were removed by suction , and each well was washed with pbs before detaching the cells using trypsin - edta . cell pellets were resuspended in 100 l of assay buffer together with 20 l of cold 6n perchloric acid ( pca ) . a 60 l aliquot was vortexed to a uniform emulsion and kept on ice for 5 min before spinning it at 13000 g for 2 min . the supernatant , containing gsh , was collected and the protein pellet discarded . for the fluorescence - based assay , a 40 l aliquot of each sample was neutralized using 6 m koh before being kept on ice for min and spun at 13000 g for 2 min at 4 c . the gsh concentration was determined by reading the absorbance of the o - phthalaldehyde ( opa ) probe at ex / em 340/420 nm after 40 min incubation at room temperature ( 10 l of the probe were added to 10 l each sample and diluted to a final volume of 100 l ) . values were normalized to the protein content of each sample determined by a bradford assay . these experiments were carried out as duplicates of triplicates in independent experiments . in all cases , independent two - sample t tests with unequal variances , welch s tests , were carried out to establish statistical significance of the variations ( p < 0.001 for * * * , p < 0.01 for * * , and p < 0.05 for * ) .
combination with redox modulators can potentiate the anticancer activity and maximize the selectivity of organometallic complexes with redox - based mechanisms of action . we show that nontoxic doses of l - buthionine sulfoximine increase the selectivity of organo - os complex fy26 for human ovarian cancer cells versus normal lung fibroblasts to 63-fold . this increase is not due to changes in the mechanism of action of fy26 but to the decreased response of cancer cells to oxidative stress .
SECTION 1. SHORT TITLE. This Act may be cited as the ``American Indian Education Foundation Act of 1999''. SEC. 2. AMERICAN INDIAN EDUCATION FOUNDATION. (a) In General.--Part B of subtitle II of title 36, United States Code, is amended by inserting after chapter 215 the following: ``CHAPTER 216. AMERICAN INDIAN EDUCATION FOUNDATION ``Sec. ``21601. Organization. ``21602. Purposes. ``21603. Governing body. ``21604. Powers. ``21605. Principal office. ``21606. Service of process. ``21607. Liability of officers and agents. ``21608. Restrictions. ``21609. Transfer of donated funds. ``Sec. 21601. Organization ``(a) Federal Charter.--The American Indian Education Foundation (herein in this chapter referred to as the `foundation') is a federally chartered corporation. ``(b) Perpetual Existence.--Except as otherwise provided, the foundation has perpetual existence. ``(c) Nature of Corporation.--The foundation is a charitable and nonprofit corporation and is not an agency or instrumentality of the United States. ``(d) Place of Incorporation and Domicile.--The foundation is declared to be incorporated and domiciled in the District of Columbia. ``(e) Definitions.--In this chapter-- ``(1) the term `American Indian' has the meaning given the term `Indian' in section 4(d) of the Indian Self-Determination and Assistance Act (25 U.S.C. 450b(d)); and ``(2) the term `Bureau funded school' has the meaning given that term in section 1146 of the Education Amendments of 1978 (25 U.S.C. 2026). ``Sec. 21602. Purposes ``The purposes of the foundation are-- ``(1) to encourage, accept, and administer private gifts of real and personal property or any income therefrom or other interest therein for the benefit of, or in support of, the mission of the Office of Indian Education Programs of the Bureau of Indian Affairs (or its successor office); ``(2) to undertake and conduct such other activities as will further the educational opportunities of American Indians who attend a Bureau funded school; and ``(3) to participate with, and otherwise assist, Federal, State, and tribal governments, agencies, entities, and individuals in undertaking and conducting activities that will further the educational opportunities of American Indians attending Bureau funded schools. ``Sec. 21603. Governing body ``(a) Board of Directors.-- ``(1) The board of directors (hereinafter in this chapter referred to as the `board') is the governing body of the foundation. The board may exercise, or provide for the exercise of, the powers of the foundation. ``(2) The number of members of the board, the manner of their selection (including the filling of vacancies), and their terms of office are as provided in the constitution and bylaws of the foundation. However, the board shall have at least 11 members, 2 of whom shall be the Secretary of the Interior and the Assistant Secretary of the Interior for Indian Affairs, who shall serve as ex officio nonvoting members, and the initial members of the board shall be appointed by the Secretary of the Interior pursuant to section 3(a) of the American Indian Education Foundation Act of 1999. ``(3) The members of the board shall be United States citizens who are knowledgeable or experienced in American Indian education and shall, to the extent practicable, represent diverse points of view relating to the education of American Indians. ``(b) Officers.-- ``(1) The officers of the foundation are a secretary, elected from among the members of the board, and any other officers provided for in the constitution and bylaws of the foundation. ``(2) The secretary shall serve, at the direction of the board, as its chief operating officer and shall be knowledgeable and experienced in matters relating to education in general and education of American Indians in particular. ``(3) The manner of election, term of office, and duties of the officers are as provided in the constitution and bylaws of the foundation. ``(c) Compensation.--Members of the board shall not receive compensation for their services as members, but shall be reimbursed for actual and necessary travel and subsistence expenses incurred by them in the performance of the duties of the foundation. ``Sec. 21604. Powers ``The foundation-- ``(1) shall adopt a constitution and bylaws for the management of its property and the regulation of its affairs, which may be amended; ``(2) may adopt and alter a corporate seal; ``(3) may make contracts, subject to the limitations of this chapter; ``(4) may acquire (through a gift or otherwise), own, lease, encumber, and transfer real or personal property as necessary or convenient to carry out the purposes of the foundation; ``(5) may sue and be sued; and ``(6) may perform any other act necessary and proper to carry out the purposes of the foundation. ``Sec. 21605. Principal office ``The principal office of the foundation shall be in the District of Columbia. However, the activities of the foundation may be conducted, and offices may be maintained, throughout the United States in accordance with the constitution and bylaws of the foundation. ``Sec. 21606. Service of process ``The foundation shall comply with the law on service of process of each State in which it is incorporated and of each State in which the foundation carries on activities. ``Sec. 21607. Liability of officers and agents ``The foundation is liable for the acts of its officers and agents acting within the scope of their authority. Members of the board are personally liable only for gross negligence in the performance of their duties. ``Sec. 21608. Restrictions ``(a) Limitation on Spending.--Beginning with the fiscal year following the first full fiscal year during which the foundation is in operation, the administrative costs of the foundation may not exceed 10 percent of the sum of-- ``(1) the amounts transferred to the foundation under section 21609 during the preceding fiscal year; and ``(2) donations received from private sources during the preceding fiscal year. ``(b) Appointment and Hiring.--The appointment of officers and employees of the foundation shall be subject to the availability of funds. ``(c) Status.--The members of the board, and the officers, employees, and agents of the foundation are not, by reason of their association with the foundation, officers, employees, or agents of the United States. ``Sec. 21609. Transfer of donated funds ``The Secretary of the Interior may transfer to the foundation funds held by the Department of the Interior under the Act of February 14, 1931 (Chap. 171; 46 Stat. 1106) (25 U.S.C. 451), if the transfer or use of such funds is not prohibited by any term under which the funds were donated.''. (b) Clerical Amendment.--The table of chapters for part B of subtitle II of title 36, United States Code, is amended by inserting after the item relating to chapter 215 the following new item: ``216. American Indian Education Foundation................. 21601''. SEC. 3. INITIAL PERIOD AFTER ESTABLISHMENT. (a) Board of Directors.-- (1) Initial board.--Notwithstanding the first sentence of section 21603(a)(2) of title 36, United States Code, not later than 6 months after the date of enactment of this Act, the Secretary of the Interior shall appoint the initial voting members of the board of directors under section 21603 of title 36, United States Code (hereinafter in this section referred to as the ``board''). The initial members of the board shall have staggered terms (as determined by the Secretary of the Interior). (2) Successive boards.--The composition of all successive boards after the initial board shall be in conformity with the constitution and bylaws of the American Indian Education Foundation organized under chapter 216 of title 36, United States Code (hereinafter in this section referred to as the ``foundation''). (b) Administrative Services and Support.-- (1) Provision of support by secretary.--Subject to paragraph (2), during the 5-year period beginning on the date of enactment of this Act, the Secretary of the Interior-- (A) may provide personnel, facilities, and other administrative support services to the foundation; (B) may provide funds to reimburse the travel expenses of the members of the board under section 21603(c)(2) of title 36, United States Code; and (C) shall require and accept reimbursements from the foundation for any-- (i) services provided under subparagraph (A); and (ii) funds provided under subparagraph (B). (2) Reimbursement.--Reimbursements accepted under paragraph (1)(C) shall be deposited in the Treasury to the credit of the appropriations then current and chargeable for the cost of providing services described in paragraph (1)(A) and the travel expenses described in paragraph (1)(B). (3) Continuation of certain services.--Notwithstanding any other provision of this section, the Secretary of the Interior may continue to provide facilities and necessary support services to the foundation after the termination of the 5-year period specified in paragraph (1), on a space available, reimbursable cost basis.
American Indian Education Foundation Act of 1999 - Establishes and grants a Federal charter to the American Indian Education Foundation.
the calcifying epithelial odontogenic tumor ( ceot ) is also known as pindborg tumor . the dutch pathologist , dr . jens jorgen pindborg , described and designated ceot as a distinct pathologic entity in 1955 . it is a benign , locally invasive neoplasm that constitutes about 1% of all odontogenic neoplasms . ceot usually presents in patients aged between 30 and 50 years and both sexes are equally affected . molar and premolar regions of the posterior mandible are the most common sites of intraosseous occurrence . ten percent of ceots occur extraosseously , with a predilection to the anterior gingival region . more than half ( 53% ) of these tumors are associated with an unerupted teeth , most commonly , mandibular molars . clear cell , noncalcifying , bone and cementum forming and langerhans cell variants have been reported . pigmented variants of odontogenic tumors are extremely rare and only 47 cases have been reported , of which 20 cases were reported in calcifying cystic odontogenic tumors ( ccot ) and one case was described as unclassifiable . however , no definitive case of pigmented ceot has been reported in literature so far . the histogenesis of pindborg tumor has not been established conclusively ; however , most authors accept that intraosseous tumors arise from the stratum intermedium of the enamel organ whereas extraosseous tumors originate from the epithelial rests of the dental lamina or from the basal cells of gingiva . tumors which arise in the maxilla tend to be more locally aggressive than those which arise in the mandible . a 28-year - old female patient visited the dental outpatient department of our institute with a complaint of swelling in the left maxillary region for the past 6 months . intraoral examination revealed a 3.5 cm 3 cm swelling , extending from the left molar to the left incisor region . radiograph revealed a mixed pattern revealing a radiolucent mass with scattered radiopaque areas associated with an unerupted tooth fragment . computerized tomography ( ct ) scan revealed a heterogeneous soft - tissue mass , epicentering the alveolar margin of the left maxilla around the root of the first molar tooth and measuring 3.6 cm 3.3 cm 3.2 cm , causing expansion with resultant thinning of the bony wall and a thin rim of calcification in the periphery [ figure 1a and b ] . an eccentrically located small , unerupted tooth fragment measuring 8 mm 6 mm 6 mm was also identified [ figure 1a ] . paraffin - embedded tissues were cut into 4-mm sections , stained with hematoxylin and eosin ( h and e ) , congo red and masson - fontana . immunohistochemistry with monoclonal mouse anti - s100 antibody ( dako carpenteria , ca , usa ) and monoclonal mouse anti - melanoma ( hmb45 ) antibody ( biogenex , san ramon , ca , usa ) was performed . ( a ) axial section reveals a heterogeneous soft - tissue density lesion ( black arrows ) , filling the left maxillary antrum . ( b ) axial section shows the lesion ( black arrows ) in the left maxillary antrum , causing expansion with resultant thinning of the bony wall and thin rim of calcification in the periphery microscopic examination of h and e - stained sections demonstrated a tumor composed of epithelial cells arranged in sheets , nests , plexiform and occasional pseudoglandular pattern . these epithelial cells were polyhedral with abundant dark staining eosinophilic cytoplasm , large vesicular nuclei with smooth nuclear margins and fine chromatin , separated by loose connective tissue stroma [ figure 2a ] . epithelial cells were admixed with cells containing abundant brownish black pigment [ figure 2b ] . homogeneous eosinophilic material , which is pathognomonic of ceot , was found in the intercellular areas [ figure 2c and f ] . numerous foci of calcification and calcific spherules forming liesegang rings [ figure 2d and g ] , ossification [ figure 2e ] and acanthomatous areas were also observed . homogeneous eosinophilic material stained positive with congo red and therefore is an amyloid - like material [ figure 3a ] . melanin bleach using potassium permanganate and masson - fontana staining [ figure 3b ] demonstrated that the pigmented cells contained melanin . immunohistochemistry revealed strong positivity for s100 [ figure 3c ] and hmb45 [ figure 3d ] in all pigment - containing cells . ( a ) polyhedral epithelial cells in sheets , plexiform and occasional pseudoglandular arrangement having abundant dark staining eosinophilic cytoplasm are separated by loose connective tissue stroma ( h&e , 100 ) . ( b ) abundant brownish black pigment containing cells admixed among tumor cells ( h&e , 200 ) . ( c ) tumor cells with intercellular areas showing homogeneous eosinophilic material undergoing calcification ( h&e , 100 ) . ( d ) foci of calcific spherules forming liesegang rings ( h&e , 40 ) . ( f ) polyhedral cells with acellular material undergoing calcification ( h&e , 100 ) globular calcifications with onion skinning ( liesegang rings ) ( h&e , 40 ) special stains and immunohistochemistry . ( a ) masson - fontanna stain showing strong positivity in the pigments , demonstrating the presence of melanin ( masson - fontanna stain , 100 ) . ( b ) congo red stain showing positivity in the homogeneous eosinophilic amyloid - like material ( congo red stain , 100 ) . ( c ) anti - s100 antibody showing positivity in round and spindled pigment - containing cells ( ihc stain , 200 ) . ( d ) anti - hmb45 antibodies showing positivity in pigment - containing cells ( ihc stain , 200 ) microscopic examination of h and e - stained sections demonstrated a tumor composed of epithelial cells arranged in sheets , nests , plexiform and occasional pseudoglandular pattern . these epithelial cells were polyhedral with abundant dark staining eosinophilic cytoplasm , large vesicular nuclei with smooth nuclear margins and fine chromatin , separated by loose connective tissue stroma [ figure 2a ] . epithelial cells were admixed with cells containing abundant brownish black pigment [ figure 2b ] . homogeneous eosinophilic material , which is pathognomonic of ceot , was found in the intercellular areas [ figure 2c and f ] . numerous foci of calcification and calcific spherules forming liesegang rings [ figure 2d and g ] , ossification [ figure 2e ] and acanthomatous areas were also observed . homogeneous eosinophilic material stained positive with congo red and therefore is an amyloid - like material [ figure 3a ] . melanin bleach using potassium permanganate and masson - fontana staining [ figure 3b ] demonstrated that the pigmented cells contained melanin . immunohistochemistry revealed strong positivity for s100 [ figure 3c ] and hmb45 [ figure 3d ] in all pigment - containing cells . ( a ) polyhedral epithelial cells in sheets , plexiform and occasional pseudoglandular arrangement having abundant dark staining eosinophilic cytoplasm are separated by loose connective tissue stroma ( h&e , 100 ) . ( b ) abundant brownish black pigment containing cells admixed among tumor cells ( h&e , 200 ) . ( c ) tumor cells with intercellular areas showing homogeneous eosinophilic material undergoing calcification ( h&e , 100 ) . ( d ) foci of calcific spherules forming liesegang rings ( h&e , 40 ) . ( f ) polyhedral cells with acellular material undergoing calcification ( h&e , 100 ) globular calcifications with onion skinning ( liesegang rings ) ( h&e , 40 ) special stains and immunohistochemistry . ( a ) masson - fontanna stain showing strong positivity in the pigments , demonstrating the presence of melanin ( masson - fontanna stain , 100 ) . ( b ) congo red stain showing positivity in the homogeneous eosinophilic amyloid - like material ( congo red stain , 100 ) . ( c ) anti - s100 antibody showing positivity in round and spindled pigment - containing cells ( ihc stain , 200 ) . ( d ) anti - hmb45 antibodies showing positivity in pigment - containing cells ( ihc stain , 200 ) classically , ceot is comprised of polygonal epithelial cells with eosinophilic cytoplasm , well - defined cellular borders and vesicular nuclei with conspicuous nucleoli . mild to moderate pleomorphism can be found , but atypical mitotic figures are usually absent . this amyloid - like material , proposed to be derived from degradation of keratin filaments secreted by the epithelial cells , stains positive with congo red and is characteristic of pindborg tumor . another important distinguishing feature of ceot is the presence of calcifications ranging from small to large aggregates or in the form calcific spherules forming concentric laminations known as liesegang rings . five histopathologic patterns have been described in pindborg tumor : sheets and islands of polyhedral cells with well - defined cell outlines and intercellular bridges ; a cribriform pattern with the presence of eosinophilic substance resembling amyloid within the spaces , which undergoes calcification to form liesegang rings ; abundant polyhedral neoplastic cells admixed with many multinucleated giant cells ; polyhedral cells in nests resembling salivary gland tumors ; and predominantly pseudoglandular pattern composed of clear cells . in general , ceots are benign with an indolent biological behavior and a local recurrence rate of 10%15% . it is important to recognize the variants of pindborg tumor because of their varied clinical course , aggressiveness , recurrence potential and malignant behavior . clear cell variant is characterized by the presence of abundant clear cells in the pseudoglandular pattern . the origin of clear cells is not clear and may arise from degenerated epithelial cells with glycogen , langerhans cells or odontogenic epithelium . the absence of calcification in the noncalcifying variant is a sign of poor tumor differentiation and is associated with greater chances of recurrence . bone and cementum forming variant shows extensive mineralized areas , either cellular resembling bone or acellular areas resembling cementum and composed of collagen . collagen is most likely deposited by stimulated stromal cells of the tumor on any calcified nidus . langerhans cell variant is distinguished by its occurrence in the asian population , involvement of anterior part of the maxilla , few nests and islands of clear tumor cells exhibiting positivity with s100 and cd1a , lack of calcification , excess of amyloid - like substance and presence of chronic inflammatory cells . langerhans cells are claimed to play a major role in antigen presentation and regression of the tumor . some authors suggest that the lesional odontogenic tissue has the potential to undergo neuroectodermal differentiation under certain situations and could give rise to melanocytes . others propose that the process of odontogenesis is multifarious and occurs as a result of close and mutual interactions involving oral epithelium and ectomesenchyme , which in turn is derived from cranial neural crest . hence , melanocytes which are also derived from neural crest might be present in odontogenic lesions . a few other authors identified the presence of melanocytes in outer enamel epithelium and dental lamina in fetuses during early gestation ( 1218 weeks ) and hence stated that melanocytes could be seen in odontogenic lesions . the same authors observed that the occurrence of pigmented lesions and melanocytes is common in pigmented races and suggested a strong racial predilection for these lesions . an additional speculation for the presence of melanocytes in odontogenic lesions includes the migration of melanocytes through the mesenchyme . in dog fetuses , the melanocytes were seen surrounding mesenchymal tissue in the dental anlage . it is observed that most of the pigmented odontogenic lesions have a prominent mesenchymal component either as in the form of dentin or in the form of calcification suggesting that the presence of calcification or dentin may activate the melanocytes previously present there , to form pigment . takeda et al . demonstrated two types of pigment - containing cells : s100-positive spindle or round cells and hmb45-positive dentritic and spindle cells derived from melanocytes . while pigmented variants of ccot have been reported , it is not known if pigmented variants of ceot occur . here , we report the first case of pigmented variant of ceot in the jaw . the tumor was found in a young asian female in the left maxilla and was associated with an unerupted tooth . the tumor was extensively calcified , and it is possible that ossification could have triggered melanocytes to produce melanin . the patient was asymptomatic for 18 months after surgery , indicating that the pigmented variant could be similar to conventional ceot in progression . however , prospective studies on a larger patient population are required to ascertain the prognosis of patients diagnosed with pigmented variant of pindborg tumor described in this case report . since this variant possesses unique histologic and uncommon clinical features , it may possibly create problems for differential diagnosis . therefore , it is important to recognize the occurrence of a pigmented variant of ceot . further investigation is required to unravel the biological behavior of this variant , precise origin of melanocytes and the pathological implication of their presence in the odontogenic tumors .
the calcifying epithelial odontogenic tumor ( ceot ) , also known as the pindborg tumor , is a benign locally invasive neoplasm . common variants of ceot include noncalcifying , langerhans cell , bone and cementum forming and clear cell , which have a prognostic significance . pigmented variants are known to occur in other odontogenic tumors . however , a definitive pigmented variant of ceot has not been reported in literature so far . here , we report the first case of pigmented pindborg tumor arising from the maxilla in a young female . the pigment was demonstrated as melanin by staining and confirmed by immunohistochemistry . the pigmented variant of ceot did not recur within 18 months postsurgery . our report indicates that it is essential to recognize the pigmented variant . we discuss the common variants of ceot and potential histogenesis of the pigmented variant . further studies are required to reveal the histogenesis of melanocytes and their pathological significance in the odontogenic tumors .
one of the most important tasks at the bioinformatics is the search for similar genetic sequences in the data banks . with the new sequencing technologies , the size of these genetics data banks are growing exponentially @xcite , and consequently the search time is growing too . the alignment algorithms , _ needleman - wunsch _ @xcite and _ smith - waterman _ @xcite are algorithms of the dynamic programming class @xcite . they are very sensible alignments algorithms , but their computation and memory costs are quadratic @xmath1 ( where @xmath2 is the input sequence length and @xmath3 the data bank length ) . this computation and memory costs turn them impractical at large data banks sets . to address this problem , heuristics was developed to reduce the memory and processing consumption of the similar sequences searching processes . among the algorithms which use heuristics for similar sequences searching , the _ fasta _ @xcite and _ _ blast__@xcite algorithms are the more used and know algorithms . these algorithms search for areas which has similarities , called _ hsp _ ( high scoring pairs ) , and then , they make the alignment of the best _ hsp _ found using a dynamic programming algorithm . the _ fasta _ and _ blast _ algorithms also optimized the alignment cost , because the alignment is made between words which have a previously detected similarity only . nevertheless , the problem complexity continues being @xmath4 ( @xmath5 is the quantity of sequences in the data banks ) because it still necessary to read the data bank sequences entirely to find the _ the searching process optimization can be made using inverted index to localize _ inverted indexes are data structures which allow to find the localization of the indexed data at constant time ( @xmath6 ) . this type of indexes are utilized at information retrieval area , especially in web searching engine , as _ google _ , _ yahoo _ , and libraries for data indexing , as the _ apache lucene _ @xcite . for the search for similar genetic sequences , the sub - sequences of the data bank sequences are indexed , eliminating the necessity of finding the _ hsps _ thought a linear search . it is quite similar with the indexes found at the end of the books , where rather than to have the text entry , it have a sub - sequences entries informing where these sub - sequence can be found . the two most common data structures which are usually used to index the genetic sequences data bank are the suffixes trees and vectors . suffixes tress are used at the work of gusfield @xcite , this data structure allows to access the sub - sequence position in linear time , but the real virtue is to find repeating sequences regions and to obtain the longest common ancestral . one example of suffixes tress application is presented by @xcite , where an algorithm for building tree to find near - exact sequences is utilized . at this example , the access time gain has a high memory consumption cost . at @xcite is said that the delcher et al . @xcite has a memory spent of @xmath7 bytes by base at her implementation when using suffixes trees . as comparison , using the human genome with approximately three billions base pairs , are necessary more than @xmath8 gigabytes to store the suffix tree . at @xcite an optimization is shown in relation to previous work , where the algorithm is three times faster and it uses one third of the memory . even with this reduction , it is necessary more than @xmath9 gigabytes to store the suffix tree to index the human genome . vector is a data structure which is mainly an array of elements , where each position of this array represents an information and inside this position , have another array informing where this information can be found . some similar searching sequences techniques that uses vectors as inverted indexes are : _ _ ssaha__@xcite , _ _ blat__@xcite , _ _ patternhunter__@xcite the _ _ miblast__@xcite , _ _ megablast__@xcite , _ _ megablast__@xcite , and kalafus @xcite which uses hash tables to align whole genomes . transforming based methods are considered out of the scope of this work , but jing @xcite presents methods that use this technique . another possible way to reduce the searching time is through parallel computing . the importance of the parallelization has grown along with the growing multiprocessing capabilities , like the number of the cores , in the modern processors . some tools for similar sequences searching have ways to use these multiprocessing technologies . as one example , it is possible to inform the _ ncbi blast _ to divide the data bank and perform parallel searches at these data banks fragments . as the data bank is divided and the search parallelized , the computational complexity is @xmath10 ( @xmath11 is the quantity of fragments that the data bank will be divided ) , or it means , even with the search parallelization , it still have a linear computation complexity . the computational complexity can be reduced using inverted index , but searching at the literature , it was not found any technique which uses indexing with parallel programming , and consequently they do not use the capacity of moderns the multi - core processors . thus , the objective of this work is to use the index techniques to optimize the searching process along with the use of the multi - core processor to reduce the searching time of the similar genetic sequences . the developed software , called _ genoogle _ uses indexing techniques with inverted index , index search parallelization , data bank division and parallelization , bit level sequences codification and alignment algorithms optimizations . this software was developed utilizing the java environment and it has a web page , web services and text mode interfaces . this work presents the _ genoogle _ , that is a similar sequence searching engine software which has as objective to execute fast and with good sensibility searches . to achieve these goals , it uses inverted index to find nimbly the _ hsps _ and it also uses parallelization techniques to use the multi - core processors capabilities . _ genoogle _ works similarly to the _ blast _ , where given an input sequence , a parameter set , and a data bank where the search will be made , the software returns the similar sequences from the given input and parameters . defining a genetic sequence as a sequence where @xmath12 = \{@xmath13 , @xmath14 , @xmath15 , @xmath16 } ( _ dna _ ) , @xmath12=\{@xmath13 , @xmath14 , @xmath15 , @xmath17 } ( _ rna _ ) and a sub - sequence is a sequence wich is contained partiality of fully into other sequence . the sequences at _ genoogle _ are divided into fixed length sub - sequences , where the length is defined by the user before the data bank formatting , and them , they are codified using @xmath18 bits for each sequence base . the sub - sequences are stored as a bit vector into @xmath19 bits integer and the length can vary from @xmath20 to @xmath21 bases . changing this value impacts at the search speed and sensibility , as big is the value , as fast will be the searching process , but the sensibility will be lower . to save memory , not overlapping windows are utilized to codify the data bank sequences , but for input sequences , to have more sensibility during the searching process , overlapped windows are utilized . these codified sequences , with other sequence information : name , identification code , and description are stored into a file disk , composing the data bank sequences . masks are used at the indexed sub - sequences to improve the searching sensibility of the inverted index . the masks are based on the _ patternhunter _ @xcite work . the masks inform which sub - sequences bases should be maintained or removed and , consequently they increase the probability to find sub - sequences at the index . the masks provide two gains : the sensibility , which allows to search at the index with not - exact sequences , and it saves index space , because longer sub - sequences will be transformed into smaller , having less index entries and less sub - sequences at the data bank . _ genoogle _ has some run time parameters which can improve the sensibility or the search performance . the parameters for the sensibility are : the maximum distance between index entries for be considered for the same _ hsp _ , the minimum _ hsp _ size and the drop off for sequences extension . changing these parameters impact on the sensibility , allows to find more _ hsp _ , but it is expected to have more false positives and to slow down the performance . _ genoogle _ use vectors as inverted indexes data structures . the size of the main vector is the quantity of possible sub - sequences : as the _ dna _ alphabet has @xmath22 letters , it is possible @xmath23 sub - sequences , being @xmath3 the defined sub - sequences length , having the inverted index @xmath23 entries . the size of each sub - sequence vector varies according the quantity of this sub - sequence into the data bank . each sub - sequence occurrence uses two integers of @xmath22 bytes to store the information : one integer is used to store the identifier of the sequence and the other integer is used to store the position at the sequence . the inverted index uses @xmath22 bytes to the sequences identifier and more @xmath22 to the position at this sequence , turning possible to index approximately @xmath24 billions ( @xmath25 ) sequences and each one can have until this length , being the available memory the major limit to the quantity of sequences and their size . [ ht ] the mask are applied at the data bank sequences during the indexing process . they are read and divided into sub - sequences , at each one the mask is applied on its sub - sequences and hence these masked sub - sequences are indexed . using masks allow having longer sub - sequences with smaller sensibility loose . for example , using the mask _ 111010010100110111 _ , where _ 1 _ means that the base in that location should be preserved and the _ 0 _ means that the base there should be removed , the sub - sequences read from the data bank will have @xmath26 bases , and after the mask be applied , will have @xmath27 bases . in this way , it is used a vector to index @xmath27 bases sub - sequences , but the sequences are divided into @xmath26 bases sub - sequences , saving inverted index structure memory . _ genoogle _ needs approximately @xmath28 bytes to store the inverted index . being @xmath29 the length of the data bank in bases , @xmath2 , the total mask length , and @xmath30 the sub - sequences length . for a data bank with @xmath22 billions bases and sub - sequences with @xmath27 bases , there will be @xmath31 of millions sub - sequences , requiring @xmath32 megabytes to store the inverted index . using masks with @xmath26 bases length , there will be @xmath33 millions sub - sequences and the inverted index will need @xmath34 megabytes , resulting on a gain of @xmath35 of the total memory required . to build the inverted indexes it is used the sort - based method @xcite and the inverted index and the formatted data bank are stored at the disk . during the _ genoogle _ start time , the whole inverted index is read and loaded into the main memory , the data bank meta informations , like file offset , are also loaded into the main memory , but the data bank sequences are read from the disk when the sequences informations are necessary . after that the inverted index and the data bank meta informations are loaded into the main memory , _ genoogle _ is ready to run the searches . the searching process is divided into @xmath36 phases : * input sequence processing ; * index searching for similar sub - sequences and construction of the _ hsps _ ; * _ hsps _ extension and merge ; * merging overlapped _ * selection of the high scored _ hsps _ ; * local alignment of the selected _ hsps _ ; * selection and exhibition of the best alignments . the input sequence processing firstly applies the mask at each overlapped sub - sequence of the input sequence and codify the resulting sub - sequence to the binary representation used by _ genoogle_. the input sequence processing is shown at fig . [ fig : input_sequence_processing ] . as the input sub - sequences are codified as binary data into an integer , it is possible to obtain the sub - sequence value directly from this data . because the determined sub - sequence position at the index is its own value it turns the index searching process simpler and direct . [ ht ] at fig . [ fig : sub_obtain ] is shown the process to retrieve the informations from the inverted index . for each masked and encoded sub - sequence from the input sequence , using its encoded value , is retrieved from the inverted index all places which have this sub - sequence at the data bank sequences . the retrieved informations are stored into an array of arrays , where each position represents a data bank sequence . if two or more retrieved information are are closer than a specified parameter , they are merged into one retrieved information . these informations are filtered by their length and the remaining ones are them called high scoring pairs ( _ hsp _ ) . the _ hsp _ have five information : initial and final positions at the input sequence and at the data bank sequence , and the length of this area , where it gets the length of the _ hsp _ in relation of the data bank and of the input sequence and get the smaller value . [ ht ] after the index searching phase , the located _ hsps _ are extended to the both directions to try to enlarge their length . during the extension phase , two or more _ hsps _ which were closed can be overlapped , generating duplicate results . hence , it is verified after the extension phase if the _ hsps _ have overlapped regions , and if they do , they are merged into one new _ hsp_. after the extension and merging phase , the _ hsps _ are sorted by their lengths in a decreasing way . it is possible to specify a parameter to inform the maximum quantity of alignments which should be returned . the objective of this parameter is to reduce the number of alignments built , saving processing and returning only the most significant alignments , it is also possible to set to return all _ hsps _ found . after the selection , it is made a local alignment for the selected _ the local alignment is built by a modified version of the _ smith - waterman _ algorithm . the alignment algorithm is modified in order to limit the distance from the main diagonal which will be used to produce the alignment . rather than to use the whole matrix to build the alignment , it is used only the closest cells of the main diagonal . this limit is used because the two sub - sequences which will be aligned have a high similarity , turning unnecessary to calculate the whole alignment matrix . to reduce the memory use , was also used a technique to divide the alignment matrix in smaller matrices . this technique divides the two sequences into segments , and each segment is aligned separately . after the segments alignment , the results are merged and considered the final result of whole sequences . after the _ hsps _ alignments , they are sorted by the alignment score , and the results are returned with other information , as the e - value , score , normalized score , and alignment position in the input and data bank sequence , to the user . to improve the searching time and to use the multi - processing capabilities , _ genoogle _ uses three parallelization techniques : inverted index access parallelization , extension and alignment parallelization , and data bank division parallelization . the data bank division parallelization is made dividing the data bank in fragments , similarly how _ ncbi blast _ does . the indexes searches and _ hsps _ construction are made independently into threads for each data bank fragment . after locating the _ hsps _ by the individual threads , they are extended , merged , sorted , filtered , aligned , sorted by their score , and returned to the user . this technique is interesting for large data banks , but this parallelization technique does not parallelize the whole searching process : the extension , sorting and alignment phases are not parallelized by this technique . analyzing the searching data bank fragmentation process , it was verified that not every searching thread have the same execution time . it happens because some fragments have more similar sequences than others . analyzing the searching time , it was verified that the index searching time represents about @xmath37 of the whole searching time . about @xmath35 of the searching time is for the _ hsps _ alignments , because it , a component was developed to parallelize the sequences extension , sorting and alignment using all available computer processing core . at this parallelization technique , the threads search the input sub - sequences at the data bank fragments index and then put the _ hsps _ into a collection shared by all index searching threads . after the index searching phase , the _ hsps _ collection is sorted by the _ hsp _ length and the longest are selected using a parameter that informs how many alignments should be returned . the remaining _ hsps _ are put into a _ fifo _ queue , where it has extenders and aligners which will perform the extension and alignment . these extenders and aligners use independent threads , they read a _ hsp _ from the queue , them perform the extension and alignment and put the result into another shared collection . these threads are managed by an executor , when a thread finish its job , the manager sends to it another _ hsp _ to extend and align until all _ hsps _ are extended and aligned . it is possible to configure the quantity of simultaneous threads . the memory required by the inverted index structure is the main problem of the data bank division . for example : using @xmath27 base pairs length sub - sequences , they are necessary @xmath19 megabytes to store only the inverted index structure . theoretically , to use the whole computational capacity of a computer with @xmath38 processing cores , it is necessary to divide the data bank in @xmath38 parts , becoming necessary to use up @xmath39 megabytes to store only the inverted index structure . because of the memory requirement for the data bank division , it is important to use a complementary approach . along with the data bank division , the input sequences are also divided and performed the search parallel . thus it is possible to parallelize the searching process without overloading the memory with more data structures . this parallelization divides the input sequence in sub - inputs , and it searches each sub - input at the inverted index independently . it is also useful because it also parallelize the input query processing . after the index search , the _ hsps _ that are from the same data bank sequence and are closer , are merged into one _ hsp_. using the data bank division in two fragments and the input sequence in two sub - inputs , they are used @xmath22 threads to search at the inverted index , being the memory overload of only two inverted indexes structures . at the fig [ fig : parallel_search ] is shown the complete parallelized _ genoogle _ search dividing the input query in two sub - inputs and the data bank in two fragments . [ fig : parallel_search ] _ genoogle _ is developed using the java environment version @xmath40 . the java environment was choose because it is multi - platform and it has a framework and primitives for parallel computing . the library _ biojava _ @xcite was used during the first part of the development , but now it was removed from the project . at the first implementations , _ biojava _ was used to reading , parsing , storing and genetic sequences alignment , but it was verified that the reading and parsing methods require too much memory , so , new and optimized classes was developed to perform these tasks . the main user interface is an text mode interface , where the user types the search command and the results are stored into a _ file that is defined by the user . this interface has commands to perform the search , to list the available data banks , to obtain the parameters list , to run the garbage collection , to run the last command executed , and to run a batch file containing commands . the batch command is interesting because with it is possible to write a file with all commands that should be executed and to inform the _ genoogle _ to execute them without any used intervention during the execution of these commands . _ genoogle _ has also an embedded simple web page interface , best suitable for testing , which contains only one input field , for the input sequence and a button to perform the search . the search results of the web page interface are a _ xml _ document formatted and shown as a _ html _ web page by a _ xsl _ document . together with the web page , _ genoogle _ has a web - services interface , implemented using _ jax - ws_. using the web - services interface , it is possible to execute queries , to set parameters , retrieve the data bank available list , and others tasks inside of a programming script . the users can write scripts to access _ genoogle _ services automatically using their preferred programming language and perform their searches without manual intervention . for the experiments was utilized a data bank with sequences of the phase @xmath41 of the human genome project @xcite along with refseq @xcite data banks . the refseq data banks were used because they are verified and they have high quality . the human genome project data bank is the _ hs_phase3 _ and has approximately @xmath42 @xmath43 . the refseq data bank are the _ cow _ with approximately @xmath44 @xmath45 , _ frog _ with @xmath0 @xmath45 , _ human _ with @xmath46 @xmath45 , _ mouse _ with @xmath47 @xmath45 , _ rat _ with @xmath48 @xmath45 , and _ zebrafish _ with @xmath49 @xmath45 , totalizing approximately @xmath50 @xmath45 . at the experiments was used the data banks from the refseq along with the _ hs_phase3 _ , totalizing @xmath51 @xmath43 and being necessary approximately @xmath18 gigabytes of memory to store it . for the execution of the experiments , they were generated @xmath27 sets of input sequences . each set has @xmath27 sequences with approximately the same size , being @xmath20 sequence got from the data bank and @xmath52 are mutations of these sequences . the sets are with sequences with @xmath53 base pair ( bp ) , @xmath54 , @xmath55 , @xmath56 , @xmath57 , @xmath58 , @xmath59 , @xmath60 , @xmath61 e @xmath62 . the searches were made using the data bank parallelism , dividing the input sequence parallelism and extending and aligning the sequences simultaneously . at the experiments it was used a computer with @xmath21 gigabytes of ram , linux version @xmath63 and java environment version @xmath40 with the _ jvm _ _ jrockit _ version @xmath64 . [ ht ] for entries up to @xmath57 the gain using the parallelism is low , giving a gain of only @xmath18 times and the total time increases when the input sequence is divided into more than @xmath22 parts . it happens because the searching time for these small input sequences are too low , less than @xmath65 , and the synchronization overload impacts directly to the searching time . for input sequences with @xmath58 it there is a gain of @xmath66 times with the utilization of the parallelization techniques . for inputs with @xmath59 and up , the speedup are @xmath38 , that is the aiming gain , and with @xmath61 and @xmath62 inputs the gains overcome this speedup . the use of tools that use suffix trees was discarded for the time comparison because of the memory required by these tools . thought tests , it was verified that the _ blat _ software can not handle data banks bigger than @xmath22 @xmath43 . _ megablast _ was not verified because @xcite says that _ megablast _ was developed to be efficient on the searching time , but the results quality is worst than _ ncbi blast _ , it happens because the seeds minimum size is @xmath67 . because of the lower results quality , it was decided not to execute experiments with this tool . the _ indexed megablast _ @xcite can not be executed because its memory requiring @xmath22 times the data bank , needing more than the @xmath21 @xmath43 available . and finally , it was not possible to obtain the _ patternhunter _ to execute the experiments . thus , it was decided to compare the performance only against the _ ncbi blast_. comparing the sequential search times of _ genoogle _ and _ blast _ it is shown that genoogle is almost @xmath0 times faster and comparing the parallel times , genoogle is @xmath68 times faster . it is interesting to realize that for smaller input , until @xmath57 , the time gains in relation with _ blast _ are not so good because the parallelization techniques does not use all their potential in these small inputs . the time difference at bigger inputs comes until @xmath69 times for @xmath60 input . it is important to realize that the sequential version of genoogle is faster than the parallel executions of the _ blast_. .time comparison between sequential ncbi blast and sequential genoogle . [ cols= " > , > , > , > " , ] the results quality was analyzed comparing the genoogle results against the blast results and verifying which _ hsps _ were identified as similar and what is the percentage of _ hsps _ that were identified by _ blast _ and not by the genoogle . for each input sequences , a collection with the found alignments by blast was created and it is verified if these alignments were found by genoogle . it is accounted how many alignments were found and it is generated a percentage for each _ e - value _ range varying from @xmath70 a @xmath71 . following is shown the graphic which shows the proportion of alignments found by genoogle in relation to the blast according the alignment _ e - value_. this graphic was generated from the data where it was verified which of the alignments found by the blast were found by the genoogle too . in this graphic it is possible to observe that until the _ e - value _ @xmath72 more than @xmath73 of the alignments were found by the _ genoogle_. until the _ e - value _ @xmath74 more than @xmath37 of the alignments were found and with the _ e - value _ @xmath75 almost @xmath76 of the alignments were found . above this _ e - value _ the quantity of alignments found is bellow @xmath77 . [ ht ] analyzing this graphic is realized that the genoogle is a good tool to find alignments with the _ e - value _ lower than @xmath78 . it happens because alignments with this _ e - value _ are usually long , with more than @xmath79 , and consequently are found easily . from the _ e - value _ @xmath80 there is a drop in the results quality , where it is stabilized close to the _ e - value _ @xmath20 . alignments with the _ e - value _ highest than @xmath81 are alignments which can not be possible to infer a close homology @xcite . this , it can be observed that genoogle has a very good search quality until the maximum @xmath82 _ e - value _ , but it has a quality drop until @xmath83 . the alignments should not to be considered to homology inference for values higher than @xmath84 . the experiments showed that the genoogle quality results is comparable to the blast when the alignment _ e - value _ is representative , demonstrating a possible homology between the two aligned sequences . more sensible search can be archived changing the searching parameters , as the maximum distance between the sub - sequences information got from the index , and the minimum hsp length . changing the minimum hsp length for alignments with _ e - value _ higher than @xmath85 , the hsp found for this _ e - value _ grew to approximately @xmath86 and the search time was raised only @xmath87 . this work presented a genetic similarity sequences searching software which uses data bank sequences indexing along with parallel computing . to ensure the effectiveness and the search quality of to use index and parallel computing was developed and implemented the genoogle tool . this software was implemented using the java @xmath40 and it can be executed at windows , linux , and mac environment . experiments were executed to verify the results execution time and the results quality . the searching time was really good , with speedup of more than @xmath0 times in relation to parallelized blast . the results quality was good , finding relevant alignments , but it can be optimized by changing the searching parameters . thus , merging the indexing techniques with the three parallelization techniques and the option to optimize the search configurations , genoogle proved to be an effective tool and its results have good quality . as the main contributions of this work , it should be noted primarily as the first tool in the literature to do the genetic sequences search using indexing and parallel computing . considering that parallel computing importance has increased with increasing number of cores at the processors and also the importance of the data indexing to optimize the searching process in data banks wich has an exponential grow , this work has a relevance for addressing these two issues together .
the search for similar genetic sequences is one of the main bioinformatics tasks . the genetic sequences data banks are growing exponentially and the searching techniques that use linear time are not capable to do the search in the required time anymore . another problem is that the clock speed of the modern processors are not growing as it did before , instead , the processing capacity is growing with the addiction of more processing cores and the techniques which does not use parallel computing does not have benefits from these extra cores . this work aims to use data indexing techniques to reduce the searching process computation cost united with the parallelization of the searching techniques to use the computational capacity of the multi core processors . to verify the viability of using these two techniques simultaneously , a software which uses parallelization techniques with inverted indexes was developed . experiments were executed to analyze the performance gain when parallelism is utilized , the search time gain , and also the quality of the results when it compared with others searching tools . the results of these experiments were promising , the parallelism gain overcame the expected speedup , the searching time was @xmath0 times faster than the parallelized _ ncbi blast _ , and the searching results showed a good quality when compared with this tool . the software source code is available at https://github.com/felipealbrecht/genoogle .
telocytes ( tcs ) are a recently described type of stromal cells defined by their ultrastructural and morphological features . telopodes ( particularly long and thin prolongations ) are the hallmark of this cell type as seen in several organs by electron microscopy [ 28 ] , and have also offered a strong indication of tcs presence in cell cultures of different origins [ 911 ] . although it has been shown that various proportions of tcs express c - kit , cd34 , caveolin-1 or vegf in vivo and in vitro , the identification of additional molecular markers is still a challenge . therefore , we took advantage of laser capture microdissection ( lcm ) , which offers the possibility of isolating a single cell with particular morphology from tissues or cultures and enables their further accurate investigation . micrornas ( mirs ) are small , single - strand rna molecules that regulate protein levels by repressing gene translation [ reviewed in 13 ] . mirs can show tissue- and cell - type - specific restriction , have distinct expression patterns during differentiation and are involved in various pathological processes . mir-1 , mir-133a and mir-208a are preferentially expressed in cardiomyocytes ( cmc ) and other muscle cells and are necessary for proper skeletal and cardiac muscle development and function . they also play a role in cardiac hypertrophy , preconditioning or ischemia - reperfusion injury . mir-199a is up - regulated in hypertrophic heart , when it is predominantly expressed in cmc , but was also detected at low levels in cardiac fibroblasts . several reports indicate that mir-21 , mir-22 , mir-29 and mir-193 are expressed in embryonic and adult fibroblasts [ 17 , 18 ] . mir-21 is also detected in cardiac fibroblasts , with levels selectively increased in interstitial fibrosis and cardiac hypertrophy . it has been shown that mir-29 plays a role in cardiac fibrosis through down - regulation of mirs encoding collagens and extracellular matrix proteins . very recently , mir-193 was found to repress c - kit expression in acute myeloid leukaemia , functioning as a tumour suppressor gene . in this study , we have investigated whether mirs known to be present and to play a functional role in myocardium are expressed in tcs isolated by lcm from cultured murine cardiac cells . healthy adult c57 black mice were used in accordance with ethical guidelines to harvest heart tissue . after mechanical mincing , small fragments were rinsed in hbss without calcium or magnesium and incubated in type ii collagenase ( sigma - aldrich , st . louis , mo , usa ) at a concentration of 250 u / ml for 15 min . at 37c . collagenase was inhibited using ice - cold hbss and the resulting cell suspension was centrifuged , washed in culture medium and seeded at a density of 1 10 cells / cm in plastic culture dishes . culture medium was dmem - f12 ( invitrogen , carlsbad , ca , usa ) supplemented with 10% foetal calf serum . after 5 to 7 days , cells were detached using trypsin - ethylenediaminetetraacetic acid and replated at lower densities ( 12 10 cells / cm ) in duplexdish 50 plates ( carl zeiss microimaging gmbh , jena , germany ) , a pen membrane - covered culture dish that allows further laser microdissection of target cells . we also used controls consisting of both 3t3 fibroblasts in culture and cell suspensions enriched in murine cmc obtained through gradient centrifugation of collagenase - dissociated murine heart tissue . cell cultures were washed with phosphate - buffered saline and then fixed with absolute ethanol , giemsa stained and air - dried . this allowed for a better visualization of morphology details as compared to phase - contrast examination . lcm was performed with the palm microbeam system ( carl zeiss microimaging gmbh ) , with 10 to 40 objectives and in accordance with the manufacturer protocols . the criteria used for tc identification were : mononucleated small cells with at least one process longer than 50 m and thinner than 0.5 m , with moniliform dilations . control cells with fibroblast morphology , but no telopodes , were also microdissected . in two separate experiments we harvested a total of 500 tcs and 500 control cells . cells were catapulted into 500 m tube caps filled with 30 m of lysing and extraction buffer . total rna was extracted with tri reagent ( sigma - aldrich ) and isolated using the protocol recommended by the manufacturer . the rna samples were evaluated with nanodrop nd-1000 spectrophotometer ( thermo scientific , waltham , ma , usa ) . for first - strand cdna synthesis we used quantimir rt ( system biosciences , san francisco , ca , usa ) according to manufacturer instructions . basically , small rnas were poly - a tailed , and an oligo - dt adapter was annealed to serve as a reverse - transcription primer . cdna templates were then quantified in a real - time sybr green qpcr reaction ( icycler system and software , bio - rad , hercules , ca , usa ) using universal reverse primers and mir - specific forward primers . mouse u6 snrna and rnu43 were used as endogenous control assays and for data normalization . numbers obtained were subtracted from an arbitrary value , and the resulting score was used to assess specific mir relative expression levels . of three experiments and two - tailed p - values of less than 0.05 were considered as statistically significant . healthy adult c57 black mice were used in accordance with ethical guidelines to harvest heart tissue . after mechanical mincing , small fragments were rinsed in hbss without calcium or magnesium and incubated in type ii collagenase ( sigma - aldrich , st . louis , mo , usa ) at a concentration of 250 u / ml for 15 min . at 37c . collagenase was inhibited using ice - cold hbss and the resulting cell suspension was centrifuged , washed in culture medium and seeded at a density of 1 10 cells / cm in plastic culture dishes . culture medium was dmem - f12 ( invitrogen , carlsbad , ca , usa ) supplemented with 10% foetal calf serum . after 5 to 7 days , cells were detached using trypsin - ethylenediaminetetraacetic acid and replated at lower densities ( 12 10 cells / cm ) in duplexdish 50 plates ( carl zeiss microimaging gmbh , jena , germany ) , a pen membrane - covered culture dish that allows further laser microdissection of target cells . we also used controls consisting of both 3t3 fibroblasts in culture and cell suspensions enriched in murine cmc obtained through gradient centrifugation of collagenase - dissociated murine heart tissue . cell cultures were washed with phosphate - buffered saline and then fixed with absolute ethanol , giemsa stained and air - dried . this allowed for a better visualization of morphology details as compared to phase - contrast examination . lcm was performed with the palm microbeam system ( carl zeiss microimaging gmbh ) , with 10 to 40 objectives and in accordance with the manufacturer protocols . the criteria used for tc identification were : mononucleated small cells with at least one process longer than 50 m and thinner than 0.5 m , with moniliform dilations . control cells with fibroblast morphology , but no telopodes , were also microdissected . in two separate experiments we harvested a total of 500 tcs and 500 control cells . cells were catapulted into 500 m tube caps filled with 30 m of lysing and extraction buffer . total rna was extracted with tri reagent ( sigma - aldrich ) and isolated using the protocol recommended by the manufacturer . the rna samples were evaluated with nanodrop nd-1000 spectrophotometer ( thermo scientific , waltham , ma , usa ) . for first - strand cdna synthesis we used quantimir rt ( system biosciences , san francisco , ca , usa ) according to manufacturer instructions . basically , small rnas were poly - a tailed , and an oligo - dt adapter was annealed to serve as a reverse - transcription primer . cdna templates were then quantified in a real - time sybr green qpcr reaction ( icycler system and software , bio - rad , hercules , ca , usa ) using universal reverse primers and mir - specific forward primers . mouse u6 snrna and rnu43 were used as endogenous control assays and for data normalization . numbers obtained were subtracted from an arbitrary value , and the resulting score was used to assess specific mir relative expression levels . the data are represented as mean + s.d . of three experiments and two - tailed p - values of less than 0.05 tcs are present in primary and first - passage cultures of murine cardiac tissue , as revealed by their typical morphology . primary cultures had higher levels of debris and non - stromal cell types and reached 80% confluence 5 to 7 days after seeding . two to 4 days after replating , variable numbers of tcs were visible , together with cells having fibroblast - like morphology ( e.g. spindle shaped , with a few short and thick end - processes ) . figure 1 shows the typical morphology of tcs that were harvested , as well as cells that were used as a negative control for mir expression relative quantification . cells were isolated within 48 hrs of their staining and kept at 4c between procedures . laser microdissection of giemsa - stained tcs in ( a ) and control cells ( c ) in ( b ) cultivated on membrane dishes . insets show the corresponding areas after microdissection and correspond to areas enclosed in red discontinuous lines . 20 objective . in order to validate our method in terms of specificity and sensitivity , we have tested the expression of several mirs known to be preferentially expressed in different types of cells within cardiac tissue ( fig . , the cmc - specific mirs , mir-133a and mir-208a , show high level of expression in the samples enriched in cmc ( fig . 2a ) , whereas mir-21 , mir-29 and mir-199a-5p are preferentially expressed in cultured cardiac cells ( ccc ) and in fibroblasts ( fig . noteworthy , mir-193 is expressed at lower level in ccc than in 3t3 fibroblasts , suggesting that , besides of cardiac fibroblasts , the cultures may contain cells where this mir is down - regulated ( fig . expression levels of mirs specifically up - regulated in cmc ( a ) or in both cultured cardiac interstitial cells and nih3t3 fibroblasts ( b ) . cmc - specific mirs are not expressed by tcs , as expected . microdissected tcs and control cells did not express any of the cmc - specific mirs ( mir-1 , 133a or 208a ) , but , in accordance with their mesenchymal origin , showed various levels of mir-21 , 22 , 29 and 199a-5p ( fig . the results represent real - time pcr data were u6 snrna is the internal control . ( a ) mir-1 , mir-133 and mir-208a are not detected ; the interstitial cell specific mirs mir-21 , mir-22 , mir-29b and mir-199a-5p are present in both fibroblast - like cells and tcs . in case of mir-29b , because the expression level is reduced the data variation from one experiment to another is high . ( b ) mir-193 is not expressed in tcs , whereas it is present in control cells . ( a , n = 2 ; b , n = 3 ) and the data are representative for two replicate experiments . mir-193 expression was below the detection level in microdissected tcs , whereas neighbouring fibroblasts - like cells were positive for it ( fig . the result correlates with the lower detection of mir-193 in ccc than in fibroblasts ( fig . 2b ) because the cardiac culture contains both types of cells , positive and negative for mir-193 . the data support the view that tcs are a distinct cell type also in terms of gene expression and regulation pathways . noteworthy , c - kit is predicted by targetscan ( http://www.targetscan.org ) to be a target of mir-193 , an interaction that has been validated experimentally . thus , our results concur with previous observations that cardiac tcs can be differentiated in situ from surrounding stromal cells by their c - kit expression . other predicted targets of mir-193 include matrix metallopeptidase 19-an enzyme that facilitates cell motility by breaking down extracellular matrix in normal processes such as tissue remodelling and in pathological circumstances ; guanine nucleotide exchange factor 12-a gtpase involved in repulsive guidance of cell migration and the chromobox protein cbx7 that positively regulates e - cadherin expression by interacting with the histone deacetylase protein 2 . in conclusion , a functional picture of tcs is emerging , where this particular type of stromal cells is responsible , as opposed to canonical fibroblasts , for establishing and maintaining tissue scaffold that is involved in cell guidance and cell - to - cell signalling . moreover , we think that tcs act in tandem with cardiac ( progenitor ) stem cells [ 25 , 26 ] .
abstracttelocytes ( tcs ) are a particular type of interstitial ( stromal ) cells defined by very long , moniliform telopodes . their tissue location , between blood vessels and other cells such as cardiomyocytes ( cmc ) and neurons , suggests a role in intercellular signalling . in order to define a microrna ( mir ) signature in cardiac tcs , we have found that mir-193 is differentially expressed between tcs and other interstitial cells . because mir-193 regulates c - kit , our data support the previous finding that tcs express c - kit in certain circumstances . in addition , the mirs which are specific to cmc and other muscle cells ( e.g. mir-133a , mir-208a ) are absent in tcs . overall the data reinforce the view that tcs are a particular type of interstitial ( mesenchymal ) cells .
it has been known for some time that in the limit of arbitrarily large heavy quark masses that qcd has a symmetry which relates hadrons with two heavy quarks ( anti - quarks ) to analogous states with one heavy anti - quark ( quark ) @xcite . we will refer to this symmetry as the doubly heavy diquark antiquark ( dhda ) symmetry . presumably when the masses are finite , but very large , a remnant of this dhda symmetry will survive in the form of an approximate symmetry . a key issue is how large must the masses be before such an approximate dhda symmetry is manifest in a useful way . the issue is particularly relevant for charm quarks both because the charm quark is the lightest of the heavy quarks and hence the approximation is most likely to fail and because doubly bottomed hadrons ( or hadrons with a charm and a bottom ) are presumably more difficult to create and detect than doubly charmed ones . the issue remained of only marginal importance in the absence of observed doubly heavy hadrons . however , in the past several years , the selex collaboration has reported the first sighting of doubly charmed baryons @xcite . four states , @xmath0 , @xmath1 , @xmath2 , and @xmath3 ( which have been interpreted as two pairs of iso - doublets ) are reported , as shown in fig . [ fig : specxi ] . it should be noted that all four states were identified through their weak decay products . this is surprising as one would ordinarily expect the excited states to decay electro - magnetically much more rapidly and thus wash out a signal for weak decays . this issue creates a potential problem for any interpretation of the data . additionally , most recently , babar has reported that they have not observed any evidence of doubly charmed baryons in @xmath4 annihilations @xcite . however , we would set these issues aside and take the existence of all four states as given to ask whether the properties of these states could be understood at least qualitatively in terms of the dhda symmetry . recently refs . @xcite and @xcite argued that the splitting between the lower doublet and the upper doublet @xmath5 states can be understood semi - quantitatively ( at the 30% level ) in terms of an approximate dhda symmetry . spectrum of @xmath6 that have been observed by the selex collaboration @xcite . ] this paper critically examines the extent to which an approximate dhda symmetry could be present for charm quarks . this is of importance both for the doubly charmed states found by selex and also for the existence of putative doubly charmed tetraquarks which are known to exist in the heavy quark limit @xcite and in potential models @xcite . we find strong evidence to suggest that the charm quark mass is _ not _ heavy enough for the symmetry to emerge automatically of color coulombic interactions . the key issue is the degree to which scales that separate in the heavy quark limit ( and whose separations are critical to the derivation of the dhda symmetry ) in fact separate for doubly charmed systems . as we will detail below , such a scale separation probably does not hold . despite this , we will show that the presence of certain non - perturbative interactions could result in an approximate dhda symmetry in the charm sector . to begin the discussion , let us consider why one expects the dhda symmetry . physically , it arises from a diquark pair forming a tightly bound nearly point - like object . the attraction between the two heavy quarks in the diquark comes from a color coulombic interaction that is attractive in the color @xmath7 channel . if the mass of the quarks is large enough , the heavy quarks move slowly and act like non - relativistic particles in a coulombic potential . as the size of a coulombic bound state is inversely proportional to its mass ( for fixed coupling ) , in the large mass limit the diquark becomes a heavy , small object with color @xmath7 . to a good approximation it becomes a static point - like @xmath7 color source ; in this sense it acts in essentially the same way as a heavy anti - quark . this symmetry was first discussed by savage and wise @xcite in the context of relating the properties of doubly heavy baryons , @xmath8 , to those of heavy mesons , @xmath9 . to the extent that one can treat the heavy diquark as formed , one can simply use standard heavy quark effective theory ( hqet ) to describe the properties of the doubly heavy baryons . since the diquark in the doubly heavy baryon essentially acts as an antiquark , one can directly relate the properties of this system to heavy mesons . using the hqet effective lagrangain in ref . @xcite , a relationship valid at large @xmath10 for the mass difference of spin excited states between the doubly heavy baryons and heavy mesons was derived : ) is different from that in ref . @xcite by a factor of @xmath11 . this error was observed and corrected by ref . @xcite and @xcite . ] @xmath12 where @xmath13 and @xmath14 are the doubly heavy anti - baryons with @xmath15 and @xmath16 , respectively , and @xmath17 and @xmath18 are the heavy mesons with @xmath19 and @xmath20 , respectively . from the prospective of hqet , this relationship should hold to @xmath21 where @xmath22 is a typical hadronic energy and is proportional to , but not identical to @xmath23 . however as was discussed in ref . @xcite , the finite size of the diquark gives rise to corrections formally larger than this in the large mass regime . at the time of the savage and wise paper , this relationship was a prediction of the theory : doubly heavy baryons had not been discovered . the selex data will allow us to explore this relation with some real world data . before proceeding further , we should note that this analysis is based on the assumption that a spatially small and tightly bound diquark configuration exists and remains unexcited in the dynamics . the key question we address is the extent to which this assumption is true . to examine the issue of diquark excitations , a systematic treatment for the dynamics of two heavy quarks is needed . at a formal level the non - relativistic expansion of the heavy quark degrees of freedom with qcd ( nrqcd ) is the natural language to explore this issue . nrqcd was first developed by bodwin , braaten , and lepage @xcite , where it was modeled after a similar treatment in the context of qed @xcite . hqet is generally considered as an expansion in powers of @xmath24 , with @xmath25 . thereby it creates two energy scales , @xmath26 and @xmath27 . on the other hand , nrqcd requires the introduction of two new scales : the characteristic momentum , @xmath28 , and energy scale , @xmath29 , where @xmath30 is the characteristic velocity of the two heavy quarks relative to each other . with the hierarchy , @xmath31 , the characteristic regimes in terms of ( energy , momentum ) of the heavy quarks are : ( @xmath26 , @xmath26 ) , ( @xmath28 , @xmath28 ) , ( @xmath29 , @xmath28 ) , and ( @xmath29 , @xmath29 ) . these are conventionally referred to as hard , soft , potential , and ultrasoft , respectively . traditional nrqcd has been further simplified into two different effective theories , pnrqcd and vnrqcd . pnrqcd integrates out the soft momentum gluons to form heavy diquarks states with definite color , and uses these diquark states as the degrees of freedom @xcite . on the other hand , vnrqcd keeps the heavy quarks as explicit degrees of freedom while matching the effective theory at the hard scale @xcite . in all forms of nrqcd , the separation of scales creates an expansion of powers of @xmath32 . on physical grounds , one expects that the nrqcd at leading order of systems with two heavy quarks ( or anti - quarks ) ought to reduce to the hqet description of the dual problem_i.e . _ , the problem related by the dhda symmetry . recently , ref . @xcite derived the presence of dhda symmetry in the context of pnrqcd while ref . @xcite confirmed this for vnrqcd by showing the equivalence between vnrqcd and pnrqcd . it should be noted that this derivation represents a qualitatively new domain for nrqcd . traditionally , nrqcd is applied to systems with one heavy quark and one heavy anti - quark with no valance light quark degrees of freedom . the fact that the technique may be extended to problems with two heavy quarks plus additional light quark degrees of freedom is non - trivial . one central point , that should be stressed , is that the derivation is quite general and applies equally well to the problem of heavy tetraquarks as well as doubly heavy baryons . the key advantage to the nrqcd formalism is that corrections to this symmetry can be systematically incorporated by working at higher order . while it is known that the dhda symmetry must emerge in the heavy quark limit , it is not immediately clear how large the corrections to the symmetry results should be for the realistic case in which heavy quarks have large but finite mass . clearly the fundamental issue is the interplay between the diquark binding into an approximately point - like object and the extent that the diquark is point - like from the light quarks perspective ; thus both the details of the physics of the interactions between the two heavy quarks as well as the between the heavy and light quarks are essential . previous work in this area , @xcite , have concentrated their efforts on perturbative expansions of the interactions between the two heavy quarks in the framework of nrqcd , and have not dealt with heavy / light interactions . since the interactions between the heavy and light quarks are intrinsically non - perturbative , it can not be estimated directly via the techniques of nrqcd . the full expansion should be a combination of hqet and nrqcd that incorporates the mixing of perturbative and non - perturbative scales . the issue of how to attack the question of the scale of these corrections for charmed or bottom quarks is the motivation for this paper . we do this in the context of the selex data with tools motivated by nrqcd . even though we do not fully formulate the new combined expansion in this paper , we provide strong arguments suggesting the need for such a theory when dealing with doubly heavy mesons . this paper explores this issue both in terms of systematic treatment of the problem based on power counting in effective field theories and in terms of more heuristic phenomenological reasoning . we divide this paper into two major sections . in the first , we work in the large quark mass limit , and develop the consequences of the spectrum in this regime . in the second section , we work with a finite quark mass and present arguments that show the selex data is not consistent with the large mass limit , the need for a new expansion to describe this system , and the justification beyond nrqcd of the apparent dhda symmetry seen by selex . before addressing the key question of whether the charm quarks are too light for the dhda symmetry to be manifest , it is useful to consider just what implications the dhda symmetry has on the spectrum when the symmetry is manifest namely , when the quarks are sufficiently heavy . we attempt to consider the extreme limit , where all relevant scales cleanly separate . it is unlikely that the physical world exists in this limit . nevertheless , an understanding of the the physics in this extreme regime is useful in understanding the applicable expansions . there has been extensive work using a variety of models in detailing the hadronic spectrum including @xcite and @xcite among others . our focus here will be considering the spectrum in the context of a possible dhda symmetry . we will consider a more modest regime , that is intended to describe the physical world , in the next section . the first consequence we consider is qualitative namely , the existence of exotic states . the dhda symmetry in hqet was first used to relate doubly heavy baryons to heavy mesons @xcite . however , the symmetry is independent of the light quarks in the problem . formally , in nrqcd , the light quarks are govern by non - perturbative dynamics , and are thereby considered irrelevant when focusing on the heavy quarks in the large mass limit . as the dhda symmetry applies in the heavy quark limit independent of the number and state of spectator light quarks , it is sufficient to consider an ordinary heavy baryon , @xmath33 . from dhda symmetry , this state is directly related to a doubly heavy tetraquark state , @xmath34 . thus in the heavy quark limit , when the dhda symmetry is exact , the existence of heavy baryons implies the existence of doubly heavy tetraquarks . the fact that doubly heavy tetraquarks must exist in the heavy quark limit has been shown previously . this was done both based on the simple argument discussed here and in the context of an illustrative model based on pion exchange @xcite . it should be noted that while being in the regime of validity of dhda requires the existence of doubly heavy tetraquarks , the converse is not true : doubly heavy tetraquarks could be formed via other mechanisms . nevertheless , the general result is significant in that the tetraquark has manifestly exotic quantum numbers in the sense that it can not be made in a simple quark model from a quark anti - quark pair . the observation of exotic hadrons has been a longstanding goal of hadronic physics . the prediction of the existence of an exotic particle directly from qcd , albeit in a limit of the theory , is of theoretical importance in that by direct construction qcd is compatible with exotics . other exotic particles , such as a heavy pentaquark , have also been shown to exist in the heavy quark limit combined with the large @xmath35 limit @xcite . let us now turn to more quantitative issues associated with the excitation spectrum . as noted in the introduction , the formal treatment of this problem incorporates nrqcd ( for the interactions between the heavy quarks ) and hqet ( for the interactions between the heavy particles and the light degrees of freedom ) . the dhda symmetry requires each of these effective theories to be in its domain of validity . in the heavy quark limit where both expansions will work , one has @xmath36 where @xmath22 is a typical hadronic scale proportional to @xmath23 and @xmath32 , the relative velocity of the heavy quark , is typically of order @xmath37 and hence depends logarithmically on the quark mass . it should be noted that the nrqcd formalism is still valid for @xmath38 as indicated by ref . however , none of the analysis in this work depends on @xmath39 being larger than @xmath22 , and hence is consistent with the domain of validity on nrqcd . the formalism of nrqcd and its associated power counting rules remains valid for two heavy quarks in the color @xmath7 in the presence of additional light quark degrees of freedom and not just for heavy quark anti - quark systems in the color singlet in heavy mass limit . this was shown in ref . @xcite and verified in ref . @xcite . it is important to note that these effective theories have different types of excitations with qualitatively different scales . doubly heavy hadrons ( in the formal limit of very large quark mass ) have three characteristic types of excitation : 1 . excitations of order @xmath40 which correspond to the interaction of the spin of the diquark with the remaining degrees of freedom in the problem . excitations of order @xmath22 which correspond to the excitations of the light degrees of freedom . excitations of order @xmath41 which correspond to the internal excitation of the diquark . the first two types of excitations can be understood in terms of hqet while the third requires nrqcd . the essential point is that as @xmath42 the three scales separate cleanly . since these excitations all occur at disparate scales , they do not influence each other . dhda symmetry imposes many relations on the various types of excitations of various doubly heavy hadrons and their associated singly heavy ones . to enumerate these , it is useful to have a naming convention for the various doubly heavy hadrons . we will generically call the ground state a doubly heavy baryon with two @xmath43 quarks , @xmath44 , and the ground state of the tetraquark , @xmath45 , which are analogous to the heavy ( anti- ) meson , @xmath46 ( _ i.e. _ , the @xmath47 and @xmath48 mesons ) and heavy lambdas , @xmath49 . we will use the following convention to indicate various types of hadron excitations : + @xmath50 indicates an excitation of type ( a ) ; + @xmath51 indicates an excitation of type ( b ) ; + @xmath52 indicates an excitation of type ( c ) . + + in addition , we will indicate the dhda equivalence between associating baryons and mesons . let us consider the phenomenological consequences of these types of excitations . in hqet , the @xmath53 heavy spin symmetry causes states which are only different by a spin flip to have the same mass . excitations of type ( a ) are the type which will break this symmetry creating a mass difference between these states . for example , this will cause a mass difference between the spin-1 @xmath54 meson and the spin-0 @xmath55 meson . as this is the leading term to create the mass splitting , hqet dictates that this splitting is @xmath56 with corrections of @xmath57 . additionally , there are corrections to this hyperfine splitting due to pnrqcd . these corrections are related to the soft gluons that have been integrated out to construct the diquark potential . the leading corrections contribute at two loops , as shown in ref . @xcite , and are thus relative @xmath58 . this implies in a correction to the mass splitting of @xmath59 , which is formally larger than the @xmath60 corrections of hqet in the infinite mass limit . because @xmath61 is the smallest scale , these excitations should be the first excitations above the ground state . excitations of type ( b ) are all other excitations associated with the light degrees of freedom . these include orbital excitations between heavy and light components , as well as excitations within the light quark degrees of freedom . due to the light quark mass , these excitations are in the non - perturbative regime of qcd , and can only be characterized by some general hadronic scale , @xmath22 . perturbative corrections to this are , in turn , meaningless . traditional nrqcd has not been applied to systems with valance light quark degrees of freedom , and thus has ignored these excitations . hqet , on the other hand , combines these into the definitions of heavy fields from the outset , and thereby neglects them for the rest of the problem . we see here that the excitations should be qualitatively the second smallest scale . excitations of type ( c ) are internal diquark excitations . these excitations correspond to the excited levels of the color coulombic potential that binds the diquark . the binding potential is @xmath62 , where the factor of @xmath63 comes from color considerations . this leads to energy levels and energy differences of : @xmath64 the last step is justified since at the heavy quark scale , @xmath65 . this verifies that type ( c ) excitations are @xmath66 . this type of excitation should be present in both the doubly heavy baryon and tetraquark sectors as the light quark interactions are suppressed since they are @xmath67 . this leads to mass relations such as : @xmath68 since diquark excitations are @xmath66 , these are the largest excitations discussed here . the corrections to these relations can be found by considering the corrections to the color coulombic potential . in the context of nrqcd , it has been shown by @xcite that these corrections are @xmath69 at the heavy quark scale . in addition to these excitations , dhda symmetry will relate heavy mesons , @xmath70 states , to doubly heavy baryons , @xmath8 states , and relate heavy baryons , @xmath33 states , to doubly heavy tetraquarks , @xmath34 states , which otherwise have the same quantum numbers . therefore the following relations can be made : @xmath71 where @xmath55 and @xmath54 are standard spin-0 and spin-1 d - mesons , @xmath6 and @xmath72 are spin-@xmath11 and spin-@xmath73 doubly heavy baryons , @xmath49 is isospin-0 spin-@xmath11 heavy baryon , @xmath13 and @xmath74 are isospin-1 spin-@xmath11 and spin-@xmath73 heavy baryons , @xmath75 is a isospin-0 spin-0 doubly heavy tetraquark , @xmath76 , @xmath77 , @xmath78 are isospin-1 spin-0 , spin-1 , and spin-2 doubly heavy tetraquarks . the dhda symmetry can then be used to relate the mass splittings @xcite . equation ( [ eq : sw ] ) identifies the corrections to the mass splitting , but not to the dhda symmetry itself . dhda symmetry relies on the interactions between the heavy diquark and the light quark(s ) . these types of interactions , which are intrinsically non - perturbative , are not well understood in either nrqcd or hqet . therefore , to understand the corrections to the symmetry , a new power counting scheme that combines the scales of nrqcd and hqet and is consistent with the other scales in the problem is necessary to account for these interactions systematically . at this time , such a system has not been formulated . yet we can get a reasonable estimation of the corrections by considering the effects of the diquark structure compared with a point - like diquark on the dhda symmetry . this consideration is exactly the form factor of the diquark relative to the scale of the light quark wave function . the form factor can be calculated by taking the fourier transform of the square of the diquark wave function . in the limit of infinite heavy quarks , the diquark is in a coulombic wave function so the calculation is straightforward . assuming that the momentum transferred is @xmath67 , the form factor can be expanded to give the leading correction to dhda symmetry as follows : @xmath79 where @xmath80 is the corresponding `` bohr radius '' of the coulombic bound state of the diquark . thus the corrections due to dhda are @xmath81 . however , these corrections are formally smaller than the type ( a ) mass splitting correction of @xmath58 . we can translate eq . ( [ eq : sw ] ) into the previous notation , and extend the relations to include the tetraquark splittings to have : @xmath82 where all quantities represent the mass of the corresponding particles . to summarize , the doubly heavy baryons and tetraquarks will have three types of excitations which are distinct in the heavy quark limit . from these we can construct the hadronic spectrum for these particles based upon these excitations and their relative size to one another . additionally , these spectra are related to the hadronic spectra of heavy mesons and heavy baryons via the dhda symmetry . these spectra are presented in figs . [ fig : spec1 ] and [ fig : spec2 ] . hadronic spectrum for doubly heavy baryons related to heavy mesons . ] hadronic spectrum for doubly heavy tetraquarks related to heavy baryons . ] in the previous section , we have worked solely in the infinite quark mass limit to determine what the spectrum would look like in this limit . we have seen the usefulness of dhda symmetry in relating the the spectra of doubly heavy baryons to heavy mesons and doubly heavy tetraquarks to heavy baryons in this limit . we would like to use this tool to interpret the corresponding spectra with a finite massive heavy quark . as the heavy quark mass is decreased from infinity , we expect that the correction terms outlined above increase , until at a certain low enough quark mass , they become as dominant as the leading order resulting in a break down of the expansion . the discovery of doubly charmed baryons by the selex collaboration provides the first experimental data to verify the heavy hadronic spectrum described . an understanding of the selex data can provide an insight into whether dhda symmetry persists in the real world . we can surmise that the selex data , along with real world parameters , could reveal one of three possible insights into the validity of dhda symmetry for doubly charmed states . first , upon examining the data , we could find that the data supports a claim that the charm mass is heavy enough to be considered in the ideal large mass limit discussed in the previous section . if this were the case the spectrum can be easily interpreted in terms of an approximate dhda symmetry . secondly , the opposite could be true , namely that the selex data would be inconsistent with an approximate dhda symmetry . this would indicate that the charm quark mass is simply too light for the symmetry to be manifest . the last possibility is perhaps the most interesting , that data could suggest that charm quark mass is not heavy enough for the preceding argument to hold in full , but that data would still be consistent with some aspects of an approximate dhda symmetry . this last option is not unreasonable as the dhda symmetry relies on the heavy diquark to be view as point - like with respect to the light degrees of freedom . the infinite mass limit ensures the validity of this assumption , but a small - sized diquark might be achieved even with a relatively modest heavy quark mass . for this possibility to be realized dynamics beyond the simple coulombic interaction must play a central role . to determine which of these possibilities is most consistent with the selex data , we will examine the size of each of the previously mentioned excitations , as well as their corrections , and compare them with experimentally determined parameters from the selex data . before doing this , we should note a general word of caution . the fact that the excited doubly charmed states were seen only via their weak decays presents a challenge to _ any _ simple interpretation of the data . the problem is that the electro - magnetic lifetime of the excited states as estimated by any simple model should be short enough to wash out any detection of excited states via their weak decay @xcite . any simple interpretation of the selex results can not simultaneously understand the type of excitation that is observed as well as the lack of an electro - magnetic decay channel . therefore our focus here will be placing limitations on the type of excitation . the excited state seen by selex shown in fig . [ fig : specxi ] could be interpreted as either a type ( a ) spin excitation or a type ( c ) diquark excitation . type ( b ) light quark excitations are ruled out as they occur on the scale of hadronic physics which is much larger than the reported excitation . either interpretation , as we will discuss , explains aspects of the data , but neither provides a complete explanation . let us consider the case where the excited states are type ( a ) spin excitations . from our discussion of the infinite mass case , we would expect that even for a finite quark mass , these excitations would be the lowest lying occurring at @xmath56 . according to the selex data , the excitation energy is @xmath83mev . with this identification , the dhda mass splitting relations , eq . ( [ eq : sw ] ) and eq . ( [ eq : hdamass ] ) are satisfied with only a @xmath84 deficiency as has been pointed out elsewhere @xcite . this size of error is also consistent with the equations corrections of @xmath85 . this appears to correspond to a success of dhda symmetry . at this point , our predecessors , @xcite , have only verified that eq . ( [ eq : sw ] ) is satisfied . this could be satisfied because dhda symmetry is the underlying phenomenon or because of a numerical conspiracy . in order determine between these two scenarios , one needs to consider the other aspects of the spectrum and dhda symmetry . that is , are type ( c ) excitation larger than type ( a ) excitation as expected when a finite quark mass is considered , and is the spatial extent of the diquark small enough to consider it point - like ? we will first tackle the former condition . for a diquark bound solely by color coulombic interactions , the excited state must by coulombic , and the excitation energy calculated from eq . ( [ eq : coloumb ] ) is justified . from eq . ( [ eq : coloumb ] ) , we can calculate the expected excitation energy of the diquark for a charm quark mass of @xmath86 gev and a velocity of @xmath87 . this gives an excitation energy of @xmath88 mev ! this is a clear sign that the scale separation arising from the color coulombic interactions , expected for an infinite quark mass , is not present for the charm quark . the constrains on dhda symmetry need to be examined . the key issue in determining whether dhda symmetry could hold is the size of the diquark with regards to the light valance quark(s ) . this can be addressed by either looking at the size of the diquark to determine if it is nearly point - like , or to determine the size of corrections of dhda symmetry as shown in eq . ( [ eq : hdacorrect ] ) . the size of the diquark can be characterized by the rms radius of the state . for coulombic wave functions , the size of the diquark in the ground state is @xmath89 fm . clearly this is not point - like on the scale of hadronic physics . the large size of the ground state of the diquark also indicates that the excited state would be even larger . such a spatially large excited state suggests that the excited state should extend beyond the color coulombic potential . this invalidates the previous calculation , while emphasizing the absurdity of assuming that the diquark is bound deeply by the color coulombic interaction . moreover , this further indicates that the diquark must be under the influence of interactions in addition the the color coulombic potential . additionally , the corrections to dhda symmetry should be small compared with @xmath90 if the approximation is used . for the values for the charm quark , the correction can be calculated , from eq . ( [ eq : hdacorrect ] ) to be @xmath91 , which for a typical hadronic scale of @xmath92 gev is not much smaller than 1 . thus both indicators show that the real world charm quark is not heavy enough to justify the point - like nature of the doubly heavy diquark which is necessary for the dhda symmetry . it should be noted that the bottom quark has a mass marginally large enough to approach the infinite mass limit scaling . the type ( c ) excitation is @xmath93 mev , with the type ( a ) excitation being @xmath94 mev calculated from the b - meson mass splitting . additionally , the characteristic size is @xmath95 fm , and the correction to the dhda symmetry is @xmath96 . all of these numbers show that for the bottom quark the scale hierarchy is as expected and corrections are relatively small , even if the scale separation is not complete . however , presently doubly bottom baryons have not been observed experimentally . we have shown that a naive approach to dhda symmetry results in the conclusion that the charm quark is by no means heavy enough to believe that this symmetry is manifest in the real world , at least if it is to arise due to color coulombic interactions . in other words , the relatively small charm quark mass causes the corrections to the infinite massive limit to become large enough to question the expansion for the excited states . however , this does not completely rule out the possibility that dhda could hold approximately and that these excitations are type ( a ) . the color coulombic interactions are not the only interactions that the charm quarks could experience as part of a diquark or a doubly heavy baryon . since the charm quarks are not heavy enough to fall into the color coulombic region , it is reasonable to surmise that these other non - perturbative interactions could conspire in such a manner that would facilitate an approximate dhda symmetry . however , these additional non - perturbative interactions are not systematically included in nrqcd . therefore , in order to describe this system , a new expansion that combines the perturbative and non - perturbative scales of nrqcd and hqet in a systematic manner is needed . at present , such an expansion has not yet been formulated . nevertheless , by examining the properties of the interactions needed to maintain dhda symmetry , a general picture of the new theory could be made . before proceeding with a discussion of the conditions that dhda symmetry imposes on additional non - perturbative interactions , an additional comment on the color coulombic potential is needed . first , when we worked in the large mass limit , we were required to be in the regime of @xmath97 . however , with a finite massive quark this condition could be weakened to include @xmath38 . under this condition , the type(b ) and type ( c ) excitation may mix since they are at the same energy scale . nevertheless , the key issue here is whether type ( a ) and type ( c ) excitations separate . the possible inclusion of type ( b ) excitations with type ( c ) does not effect whether they are separated from type ( a ) , and hence do not effect the results discussed here . secondly , the color coulombic potential is only the leading order term in nrqcd ; sub - leading terms might need to be included when a finite massive quark is considered . however , since we have seen a need for a new expansion that includes the mixture of perturbative and non - perturbative effects , it is not clear whether the sub - leading terms suggested by nrqcd are the only sub - leading terms in the combined expansion . in both of these cases though , additional interactions beyond the simple color coulombic potential are included . it is not unreasonable that these , just like the ones hypothetically postulated above , would conspire so that the dhda symmetry would be manifest in an approximate manner in the real world . again , a description of the conditions to obtain an approximate dhda symmetry will provide insight into these additional interactions whether they are nrqcd based or well beyond the scope of nrqcd and hqet . there are two key places where the analysis based on the color coulombic potential fails to give rise to the dhda symmetry with real world parameters . the assessment of these failures will provide conditions on the additional interactions to reestablish dhda symmetry . the first is the characteristic size of the diquark . we have already shown that for the coulombic potential , the size of the diquark is large enough not to be considered even remotely point - like from the point of view of hadronic dynamics . secondly , the hierarchy of scales used to derive the result breaks down badly . additional dynamics beyond color coulombic would need to create a diquark with a size much smaller than the characteristic hadronic size and to re - establish the spin excitations as the lowest lying excitations as we originally assumed . an examination of the restrictions placed on the characteristic size of the diquark reveals the following . the characteristic size of the diquark , which we will denote as @xmath98 , must be smaller than the size in a coulombic potential , denoted @xmath99 , and it must be small enough to allow the dhda corrections to be small . the correction term of eq . ( [ eq : hdacorrect ] ) can be rewritten in terms of this characteristic size as @xmath100 . thus for the correction to be small @xmath101 . @xmath99 must be larger than @xmath102 since @xmath99 already violates dhda symmetry and thus can not be smaller than @xmath102 . therefore , in order for the diquark to be considered point - like , both @xmath103must be simultaneously satisfied . in order to insure this , in terms of size , @xmath102 could be much smaller than @xmath99 , or @xmath102 could be of comparable size to @xmath99 . consider the former possibility . @xmath104 is equivalent to @xmath105 . this implies that @xmath106 . this relationship is never satisfied since @xmath107 and @xmath108 . thus for dhda symmetry to occur the latter condition must hold . it gives : @xmath109 implying @xmath110 . as @xmath37 at the charmed quark mass scale _ is _ around @xmath111 , this relation can only be satisfied if @xmath112 . it should be noted however , that an interaction that provides a characteristic size of the diquark which is consistent with eq . ( [ eq : ldhda ] ) is possible . for the purposes of our discussion here , we needed to show that at least one kinematic region was possible , and the region where @xmath112 satisfies these conditions even though it should not be unique . a couple of comments should be made about this condition . the first is that naively appears not to occur even for the charm quark case . if one takes @xmath22 to be of the scale of @xmath23 it seems to be much smaller than @xmath113 . however , we should note that the @xmath114 indicates `` of the same scale as '' under the assumption that the coefficients which arise in the expansion are `` natural '' _ i.e. _ of order unity . if the dynamics are such that some of the coefficients multiplying @xmath22 are anomalously large , the condition @xmath115 could hold effectively . the second key point is simply that if this does occur the system is clearly beyond the perturbative regime . it should also be noted that that this should _ not _ be seen as a generic condition invalidating nrqcd . rather it implies that _ for this particular system _ the expansion has broken down . there is non - trivial evidence that this is in fact the case ; namely if one assumes that the expansion is working one gets inconsistent results . the central question addressed here is not whether the expansion has broken down , rather it is whether one can still have a small diquark even if the expansion has broken down . if it indeed is the case that the condition @xmath112 is effectively met , then there is a possible characteristic size of the charmed diquark , for which dhda symmetry could be valid . this region is simply a size that is much smaller than the length associated with the coulombic potential and smaller than the typical hadronic size . thus far we have identified a possible kinetimatic region for which approximate dhda symmetry may be possible . however , to test whether this can occur in practice , we need to see whether plausible dynamics can drive the system into such a regime . we do this by considering a `` reasonable '' dynamical model for the interaction between the heavy quarks . this model is not intended to be an accurate description of hadronic physics . the goal is simply to see whether a simple model with natural scales can put the system in the regime where dhda symmetry emerges at least approximately . the existence of a model which does this shows that an approximate dhda symmetry could be present in charm physics despite the fact that nrqcd in the coulombic regime plus hqet alone do not give rise to an approximate dhda symmetry with the real world charm quark mass . to illustrate the kind of model which brings us into this regime , we consider a linear confining potential with a string tension of @xmath116 . such a potential , with the same string tension , can be used to get a reasonable description of the @xmath117 @xcite . one might not believe that such a model is applicable at all distances , to which we will attempt to apply . indeed , one may reasonably question whether any two - body potential description is sensible . nevertheless the scales of the model are at least instructive . any confining potential that can be introduced will cause the characteristic size of the diquark to be reduced , thus the conditions on the diquark size may be satisfied . specifically for the linear confining potential above binding charmed quarks , the characteristic length is @xmath118 fm . this is substantially smaller than the coulombic wave function and might be small enough so that approximate dhda might emerge . moreover , the small size of the bound state helps to justify the two - body potential description _ a posteriori _ ; the effects of the light quark between the heavy ones should be suppressed due to the small size . unfortunately , this calculation is not part of a systematic calculation , and it is not immediately clear how to reliably estimate the size of the correction to the leading order dhda estimate for the splitting . calculations of the energy spectrum of coulombic plus linear confining potentials in this channel reveals that the radial excitation energy is @xmath119 mev , far above the @xmath120 mev energy associated with expected spin excitations . thus this linear confining potential satisfies both of the conditions needed to believe that an approximate dhda symmetry could be realized for charmed quarks . we have thus found a region where an approximate dhda symmetry could be realized approximately and the lowest lying excitations are type ( a ) spin excitations . the color coulombic interactions can not be the only relevant interactions that the heavy quarks experience ( as is assumed in the heavy quark mass limit ) . of course the question of whether the dynamics as such is realized in nature , remains an open question . even though we have provided a consistent argument for the observed excited states to be spin excitation , there remains a phenomenological issue with the parity of the excited state . type ( a ) excitations do not change the parity of the excited state relative to the ground state . ground state baryons have positive parity , thus the spin excited state should also have positive parity . experimentally , the parity of the excited states has not been determined . the selex collaboration have argued that the orbital angular momentum of the ground state is consistent with @xmath121 ( positive parity ) , while the excited state is consistent with @xmath122 ( either positive or negative parity ) . furthermore , selex observed an orbital excited state @xmath123 which has negative parity and decays via pion emission to @xmath124 suggesting that this state could have negative parity . if this parity assignment holds , the interpretation that the excited states were spin excitations , made here and in refs . @xcite , would be ruled out . now let us consider the case where the excitation is interpreted as a type ( c ) diquark excitation . type ( c ) excitations could result in a parity flip from the ground state . this would resolve the parity problem found with the spin excitation interpretation . as we will discuss below , if this scenario is correct we are almost certainly outside the regime of validity of dhda as well as outside the regime of validity of nrqcd . moreover , it is likely to be very difficult to make such a scenario work phenomenologically . in order for diquark excitations to be smaller than the spin excitations , there must be a break down of the heavy quark mass limit ; the system must reside in a non - perturbative regime . therefore , as with the previous case , the diquark can be under the influence of non - perturbative interactions beyond the color coulombic interactions . we showed that if these additional confining interactions maintained an approximate dhda symmetry , the diquark excitations were much larger than the observed @xmath83 mev excitation . again we can illustrate this with a linearly rising potential between the heavy quarks . in order for the diquark excitations to be comparable to the observed splitting , the linear confining interactions must have a string constant of @xmath125 , which is very small compared to the natural scales in the problem . the small size of the linear confining interactions results in the diquark having a larger size , and makes the assumptions that it is point - like even less believable . for the string constant of 50 @xmath126 considered here , the ground state of the diquark has an rms radius of @xmath127 fm , and the first excited state has an rms radius of @xmath128 fm . these numbers are extremely large compared to typical hadronic sizes . the preceding model calculation suggests that if the excitation were the excitation of the diquark , the dhda symmetry can not be valid even approximately . it also raises a fundamental issue of self - consistency . a large spatially extent diquark allows the light quark to come between the two heavy quarks allowing for three - body interactions to play a significant dynamical role . to the extent that this occurs , it is meaningless as a phenomenological matter to separate the diquark excitation from excitations of the entire system . thus , excitations of type ( b ) and ( c ) would strongly mix and the entire structure of scale separation would break down . we note that this analysis was based on a very simple and not terribly plausible model . however , it does incorporate the natural scales of the problem and shows that the excited state wave functions are _ much _ too large to be taken seriously . it is also clear that it would be very hard to construct any potential model which restricts the diquark size to be much less than a fermi while having an excitation energy of @xmath83 mev . to illustrate this point , we can consider a harmonic confining potential instead of the linear potential . we would expect that this potential would confine the excited state and reduce its size more than the linear potential . calculating the size of the diquark under these conditions for an excitation energy of @xmath83 mev results in a ground state rms radius of @xmath129 fm and an excited state rms radius of @xmath130 fm . even though the diquark size is smaller , it is still very large in terms of hadronic physics . furthermore , if we were able to drive the size of the excited state to a reasonable hadronic size , say , @xmath90 fm , the ground state would be even smaller . such a small ground state size is then consistent with spin excitations discussed previously . it thus seems difficult for this scenario to be correct . together these two scenarios make it very difficult to understand the data in a simple way . if the parity of the is the parity of the states is correctly interpreted by selex , there does not appear to be any simple phenomoenologically reasonable interactions yielding either small diquark excitations or dhda symmetry . however , if we set the parity designation aside , scenario i , the assignment of type ( a ) spin excitations , seems to be the more plausible interpretation . the selex data on doubly heavy baryons is very difficult to interpret . as noted in the introduction , the fact the excited states were detectable through their weak decays when there were open channels for electromagnetic decays is very problematic ; normally one would expect these to dilute the strength to the point that the states would be very difficult to see . despite this problem , we have attempted to understand the selex states in the context of dhda symmetry . we have shown that the data is not consistent with the heavy quark mass limit , but this does not rule out an approximate dhda symmetry . this could emerge if diquark interactions beyond color coulombic interactions are considered . as such , a new systematic expansion , which is a hybrid of hqet and nrqcd but outside the domain of the color coulombic , would be the most appropriate to describe the physics of doubly heavy baryons . such an expansion could help in the understanding of the selex observations . at the same time it is critical to add to our understanding of the experimental situation . in particular , it is essential that the observed states be confirmed in other experiments ; that the parity of the states are pinned down ; and the accurate measurements of electromagnetic transitions are made . these measurements are critical in understanding the doubly charm baryon spectrum as well as the validity of dhda symmetry in charm physics . m. mattson _ ( selex collaboration ) , phys . lett.*89 * , 112001 ( 2002 ) ; m.a . moinester _ et al . _ ( selex collaboration ) , czech . j. phys . * 53 * , b201 ( 2003 ) ; a. ocherashvili _ et al . _ ( selex collaboration ) , phys . lett.b * 628 * , 18 ( 2005 ) ; j. a. russ , http://www-nuclear.tau.ac.il/ murrym / jimjune2003.pdf b. aubert _ et al . _ ( babar colaboration ) , hep - ex/0605075 . a. pineda and j. soto , nucl . suppl . * 64 * , 428 ( 1998 ) ; n. brambilla , a. pineda , j. soto , and a. vairo , nucl . * b566 * , 275 ( 2000 ) ; n. brambilla , a. pineda , j. soto , and a. vairo , re . phys . * 77 * , 1423 ( 2005 ) .
in the limit of heavy quark masses going to infinity , a symmetry is known to emerge in qcd relating properties of hadrons with two heavy quarks to analogous states with one heavy anti - quark . a key question is whether the charm mass is heavy enough so that this symmetry is manifest in at least an approximate manner . the issue is crucial in attempting to understand the recent reports by the selex collaboration of doubly charmed baryons . we argue on very general grounds that the charm quark mass is substantially too light for the symmetry to emerge automatically via colour coulombic interactions . however , the symmetry could emerge approximately depending on the dynamical details of the non - perturbative physics . to treat the problem systematically , a new expansion that simultaneously incorporates nrqcd and hqet is needed .
is remarkably growing in recent years , as there is an increased demand of many clinical specialties for biomaterials able not only to substitute the lost or destroyed tissues but also to provide an environment that could induce its own regeneration . extended research has started to emerge in the field of dental tissue regeneration based on the use of stem cells in combination with various scaffolds and relevant growth and differentiation factors which make the classical tissue engineering triad . in literature , various types of biomaterial scaffolds have been developed as ecm analogs capable of supporting cell attachment , proliferation , and differentiation and , ultimately , forming new engineered tissues or organs [ 2 , 3 ] . although a wide range of biomaterials have been proposed for this purpose ( ceramics , natural or synthetic polymers , etc . ) , to date , glass , glass - ceramic , and ceramic scaffolds present important advantages compared to polymeric scaffolds , such as porous structure and chemical texture that promotes mesenchymal cells differentiation and mineralization of the extracellular matrix , lack of toxic byproducts , and the formation of dentinal tubule - like structures [ 47 ] . furthermore , ceramic scaffolds can be used as carriers of growth factors and angiogenetic agents , drugs , and cell differentiation products [ 8 , 9 ] . calcium - phosphate ( -tcp ) or hydroxyapatite ( ha ) scaffolds are the most investigated compositions for dental tissues regeneration due to their chemical resemblance to the mineral component of natural dentin in mammals . however , other ceramic compositions may be more beneficial in triggering dental tissue formation , although research in this area is limited . mg - doped phosphate glasses and ceramics have been shown to enhance the bioactivity of the scaffolds related to osteogenesis . however , to date , the effect of mg ions on dentin regeneration is largely unknown , although the use of mg - containing ceramic scaffolds for dentin regeneration seems a reasonable concept due to the increased amount of mg contained in dentin . based on the fact that magnesium plays a fundamental role in cellular processes [ 12 , 13 ] and skeletal metabolism [ 14 , 15 ] , mg - containing glass - ceramics with high porosity , suitable degradability , and bioactivity have been only recently proposed for dental tissue regeneration . huang et al . compared akermanite ( ca2mg(si2o7 ) ) and -tricalcium phosphate ( -tcp ) in their ability to induce differentiation of human mesenchymal stem cells ( mscs ) , showing that the release of si and mg significantly facilitated stem cell proliferation and differentiation . furthermore , qu et al . reported that the sustained release of mg ions from magnesium - containing nanostructured hybrid scaffolds significantly enhanced the proliferation , differentiation , and biomineralization of human dpscs in vitro . new studies over the introduction of various metallic ions when synthesizing bioactive glasses report that when used in small amounts , they could be beneficiary , since by tailoring the composition and ionic dissolution process of bioactive glasses , the stimulation of specific cell behavior may be achieved . the addition of cu ions has been proposed to show beneficial effects on angiogenesis and to induce an increase in differentiation of mscs whereas the addition of zn ion shows anti - inflammatory effects and stimulates bone formation in vitro by activating protein synthesis in osteoblasts [ 8 , 9 ] . recently biomaterials with antibacterial properties have been suggested in dental tissues engineering for the creation of a bacteria - free environment while healing and regenerating the defect area . this is particularly important for regenerating dental tissues which are prone to bacterial invasion from the oral cavity . the synthesis of three - dimensional porous scaffolds with interconnected porous structure , able to function as temporary 3d templates for cell attachment , proliferation , and differentiation when in contact under controlled environment and capable of releasing ions with antimicrobial or cariostatic properties , could constitute a suitable inductive carrier that could enhance dentin regeneration and induce the optimal formation of new dentin matrix . although the last few years mg , zn , and cu ions have shown promising results as additives or dopants to bioceramic scaffolds , the effect of their simultaneous presence in quaternary systems of sio2-cao - mgo - cuo or sio2-cao - mgo - zno has not been investigated , to the best of the authors ' knowledge . consequently , the aim of this work was to synthesize mg - based glass - ceramic scaffolds with incorporated zn / cu ions and to investigate their physical , mechanical , and biological properties . polyurethane ( pu ) foam was used as a sacrificial template in order to produce 3d porous scaffolds . the foam was cut into pieces of 10 10 5 mm and used for the fabrication of the bioactive scaffolds through the foam replica technique as described by chen et al . while it was immersed in sol - gel . briefly , teos was added in the mixture of ultrapure h2o and hno3 ( 2 n ) and stirred for approximately 30 min until partial hydrolysis of teos occurred . calcium nitrate tetrahydrate ( ca(no3)24h2o ) , magnesium nitrate hexahydrate ( mg(no3)26h2o ) , and zinc nitrate hexahydrate ( zn(no3)26h2o ) or cupric nitrate hemipentahydrate ( cu(no3)22.5h2o ) were added to the mixture allowing 50 min for the hydrolysis reaction to complete at 60c . after the immersion of the foam in the sol - gel and mechanical stirring for 5 min , the samples ( green bodies ) were retrieved from the sol - gel and squeezed in order to remove the excess of sol from the pores and then left to dry out for at least 12 h. the thickness of the bioactive glass on the green bodies was adjusted by pouring droplets of sol - gel . the excess was removed after centrifuging the green bodies . in order to understand the structural changes upon heating of the bioactive glasses , as well as their mass loss percentage , the thermogravimetric ( tg ) and differential scanning calorimetry ( dsc ) curves were received with heating rate of 10c / min from room temperature to 1400c , under nitrogen atmosphere . according to tg - dsc results , the synthesized bioactive scaffolds were sintered at 890c ( zn - based ) and 866c ( cu - based ) with 2 h annealing . fourier transform infrared spectroscopy ( ftir ) and x - ray diffraction analysis ( xrd ) were used in order to examine thoroughly the scaffold 's crystal structure . for ftir measurements a perkin - elmer spectrometer spectrum 1000 in mir region was used to determine the chemical composition of the fabricated scaffolds . representative scaffolds from both groups were ground into powder and pellets with powder to kbr ratio of 1 : 100 were fabricated under pressure ( 7 tons ) . for the xrd analysis a philips ( pw1710 ) diffractometer with ni - filtered cuka wave radiation was used . archimedes method was used for the determination of the scaffold porosity , p , as indicated by the equation(1)p = vporesvbulk , where vbulk was calculated by the mass and dimensions of the scaffolds . the morphology and microstructure of the scaffolds was monitored by the use of scanning electron microscopy with associated energy dispersive spectroscopic analysis ( sem - eds ) . the mechanical properties of the synthesized scaffolds were tested by an instron 3344 loading apparatus in compression at a crosshead speed of 0.5 mm / min . ten prismatic samples ( five from each group ) with dimensions 8 8 4 mm were tested . the compressive load was applied until 1 mm ( 12.5% ) compressive strain was achieved in the 8 mm dimension ( height ) . further loading applied during pilot experiments resulted in off - axis loading and thus the received stress values were not considered as valid . the highest stress values included in the 1 mm stress - strain curve were recorded and mean values with standard deviations were determined . degradation test was performed according to the iso 10993 - 14 : 2009 ( extreme and simulation solution tests ) . mass calculation was performed with an electronic balance ( kern abs ) with an accuracy of 0.0001 mg and the specific mass of each scaffold was recorded as the difference between the mass of the container with and without the scaffold . for the simulation solution test each container was filled with 100 ml of freshly prepared tris - hcl buffer , with ph 7.4 0.1 at 37 1c , while for the extreme solution test each container was filled with 10 ml of the buffered citric acid solution , with ph 3.0 0.2 at 37 1c . then , all containers were placed in a controlled - temperature environment at 37 0.5c , for 120 h. the containers were agitated at 2 hz with circular movement . after 120 h the containers with scaffolds were allowed to cool at room temperature . then , filter paper and scaffold 's remnants were dried in an oven overnight at 100 2c . the difference between the mass of the filter paper with and without the remnants was the actual mass of the nondegraded scaffold . finally , the difference between the initial recorded mass of the scaffolds and the mass of the nondegraded scaffold remnants was recorded as the mass of the degraded scaffold . the % weight loss was determined with the following equation : ( 2)weight loss % = wowtwo100 . the scaffolds were placed in sterilized reagent bottles and submerged in sbf solution with mass to solution ratio adjusted at 1.5 mg / ml . then they were placed in an incubator ( incucell 55 ) at 37c under renewal conditions for various times after immersion ( 6 h , 24 h , and then after every 48 h ) . finally the specimens were removed from the sbf at each time point ( after 10 and 21 days of immersion ) , washed with distilled water , and dried at room temperature . dpsc cultures were established from third molars of young healthy donors aged 1618 years and extensively characterized for several stem cell markers , as previously published by our group . the collection of the samples was performed according to the guidelines of the institutional review board and the parents of all donors signed an informed consent form . for the establishment of cell cultures the enzymatic dissociation method was used . briefly , teeth were disinfected and cut around the cementum - enamel junction to expose the pulp chamber . the tissue was minced into small segments and digested in a solution of 3 mg / ml collagenase type i and 4 mg / ml dispase ii ( invitrogen , karlsruhe , germany ) for 1 h at 37c . single cell suspensions were obtained by passing the cells through a 70 m cell strainer ( bd biosciences , heidelberg , germany ) . cells were expanded with -mem ( minimum essential media ) culture medium ( invitrogen ) , supplemented with 15% fbs ( eu - tested , invitrogen ) , 100 mm l - ascorbic acid phosphate ( sigma - aldrich , taufkirchen , germany ) , 100 units / ml penicillin , 100 mg / ml streptomycin , and 0.25 mg / ml amphotericin b ( all from invitrogen ) ( complete culture medium ( ccm ) ) , and incubated at 37c in 5% co2 . cultured dpscs in passage numbers from 3 to 6 were used for all experiments . to analyze cell viability / proliferation scaffolds were first preimmersed into ccm for 30 min at 37c and 5% co2 atmosphere in an incubator in order to adjust ph and create a more biomimetic microenvironment before cell seeding . afterwards , the medium was removed and dpscs were spotted at low volume ( 100 l ) into the scaffolds at 5 10 cells / scaffold in 48 well - plates and allowed to attach first for 45 min before being fully covered with 500 l ccm . cell viability / proliferation was evaluated after 1 , 3 , 7 , and 14 days ( d ) by the mtt assay ( n = 4 ) . medium change was performed every 3 days during the entire experimental period . at the end of each time point 50 l of mtt ( 5 mg / ml in pbs ) was added in each well and scaffolds / cell constructs were incubated for 3 h at 37c and 5% co2 . after this period , the medium containing the mtt solution was discarded , the scaffold / cell constructs were washed with pbs , and the insoluble formazan was dissolved with dmso overnight at 37c . the absorbance was measured against blank ( dmso ) at a wavelength of 545 nm and a reference filter of 630 nm by a microplate reader ( epock , biotek , biotek instruments , inc , vermont , usa ) . as controls , scaffolds ( cua2 and zna2 ) without cells were incubated under the same conditions and the optical density values were subtracted from values obtained by the corresponding scaffold / cell constructs . finally , od values were normalized to those of control dpscs cultures beginning with the same cell number ( 5 10 cells / well ) and the final results were expressed as % percentage of control . in order to evaluate cell attachment and morphology of dpscs seeded into the biomimetic scaffolds , samples of scaffold / cell constructs after 3 , 7 , and 14 d , the scaffold / cell constructs were washed twice with pbs and fixed with 3% glutaraldehyde ( in 0.1 m sodium cacodylate , ph 7.4 , containing 0.1 m sucrose ) . the specimens were subsequently dehydrated in a series of increasing concentrations of ethanol and hexamethyldisilazane . for sem analysis they were carbon - coated and observed with a jeol ( japan ) electronic microscope at 20 kv . thermal analysis of bioactive glasses can efficiently determine mass variations and thermal content changes as a function of temperature . therefore , it is critically essential to determine these variations and changes for every material , which is going to receive heat treatment , in order to be able to predict its behavior at high temperatures . as already mentioned , zna2 scaffolds were sintered at 890c and cua2 scaffolds at 866c , with 2 h annealing . those temperatures were extracted from dsc curves ( figure 1 , red lines ) for each bioactive glass and represent exothermic peaks ( tc ) . the temperature at these peaks corresponds to the crystallization of the samples , while additional exothermic peaks are observed at higher temperatures ( 1060c for cua2 and 1180c for zna2 ) . endothermic peaks assigned to the melting point ( tm ) of each sample are observed at 1257c for the cua2 and 1290c for the zna2 glasses . in this study , sintering temperatures were chosen at the first exothermic peak of each glass , in order to produce scaffolds with improved mechanical properties , as the crystallization of a glass provides a mechanically enhanced system without necessarily impairing the bioactive response of the glass - ceramic . the tg curves ( figure 1 , blue lines ) of both samples indicate that the mass variations were insignificant , being under 8% for both of them . mass loss for both bioactive glasses takes place under 600c and is caused because of the h2o , co , and co2 release from the samples , which were entrapped inside during the synthesis process . bioactive scaffolds in order to be applied for the development of calcified tissue should be able to favor cell penetration , vascularization , and nutrient and metabolic waste transportation [ 26 , 27 ] . to achieve such a goal scaffolds should exhibit interconnected porous structure with pore sizes between 300 and 500 m [ 18 , 28 ] . the porous structure and morphology of the bioactive glass - ceramic scaffolds are shown in figure 2 . the zna2 and cua2 scaffolds presented a mean porosity of 84% and 74% , respectively . a primary goal of dental tissue regeneration is the development of suitable scaffolding materials that could support dental stem cells attachment and proliferation . scaffolds of similar porosity and interconnectivity as those of the scaffolds fabricated in this study have been shown to support the attachment and proliferation of human dental pulp stem cells [ 18 , 28 ] . ftir spectra of both zna2 and cua2 glass - ceramic scaffolds present the characteristic peaks of silicate glasses shown by a broad peak at 9001200 cm and the peak at ~470 cm . in addition , the spectra of the zna2 reveal the presence of a strong peak at 796 cm indicating the existence of bridging oxygen , which are connected with the inability of a glass - ceramic material to exhibit bioactive behavior [ 30 , 31 ] . this peak though present is not so intense in the spectra of the cua2 scaffolds . for cua2 scaffolds , the ftir peaks at 646 cm , 690 cm , 902 cm , and 946 cm were attributed to wollastonite ( casio3 ) . xrd patterns ( figure 4 ) revealed that zna2 scaffolds consist mainly of an amorphous phase . on the other hand , xrd patterns of cua2 glass - ceramic scaffolds indicate the existence of wollastonite ( approximate percentage 40%wt ) , while 10%wt of calcium copper silicate ( cacusi4o10 ) was also detected . the mechanical strength of both zna2 and cua2 scaffolds under uniaxial compression stress was proven , as expected , rather low but in the range of values attained for ceramic scaffolds noncoated with gelatin or other polymeric materials [ 33 , 34 ] . more specific , zna2 glass - ceramic scaffolds presented a mean compressive strength at 0.10 ( 0.06 ) mpa and cua2 glass - ceramic scaffolds a mean compressive strength of 0.02 ( 0.007 ) mpa . as it is shown from the typical stress - strain curves presented in figure 4 , a continuous section with peaks after isolating linear elastic regions and valleys , corresponding to the brittle crushing of the struts , was the dominant mode of fracture , as has been observed for brittle ceramic porous scaffolds [ 34 , 35 ] . further improvements of the mechanical properties of the scaffolds are necessary for the maintenance of their structural integrity so as to allow time for the new calcified tissue to grow . the capability of improving the mechanical properties of ceramic scaffolds has been demonstrated in several composite polymer - ceramic formulations [ 3639 ] . it is highly possible that coating these scaffolds with gelatin or alginate hydrogel could significantly improve their mechanical behavior and this is a subject of future research . results of degradation tests are presented in figure 5 . a mean degradation rate of 3.5% ( zna2)-3.7% ( cua2 ) was recorded for the simulation test in tris buffer solution after 120 h immersion , while extreme test in citric acid solution revealed slightly higher degradation rate for the same time period ( 5% for zna2 , 7% for cua2 ) . the recorded degradation values were higher for the extreme test in comparison to the simulation test for both ceramic scaffolds ( zna2 and cua2 ) . moreover , ceramic scaffolds of zna2 presented lower degradation values in extreme degradation test , in comparison with cua2 , while the two ceramic scaffolds presented almost equal degradation values in simulation degradation test . the higher degradation rate of the cua2 compared to the zna2 scaffolds can be explained by the presence of wollastonite in the cua2 scaffolds , as it has been found that the increase of wollastonite percentage rapidly increases the mass loss of composite poly(3-hydroxybutyrate - co-3-hydroxyvalerate ) ( phbv)/wollastonite scaffolds . this increased weight loss may be attributed to the dissolution of wollastonite when immersed in aqueous solution , the release of alkaline ions , and the subsequent destruction of the three - dimensional structure of the scaffolds . the release of alkaline ions of bioactive glasses is one of the basic mechanisms of apatite formation , as it leads to the formation of a high surface area of hydrated silica and finally to the crystallization of apatite through precipitation of p and ca from the surrounding environment . the increased degradation rate may be the reason for the bioactive behavior of cua2 despite its lower porosity , while the lower degradation of zna2 that can be assigned to the presence of nonbridging oxygen as found with ftir explains its inability for in vitro apatite formation . degradation of scaffolds is necessary during calcified tissue formation , as scaffolds are networks that assist initial cell attachment and proliferation but have to degrade simultaneously with the new tissue formation . similar degradation rate values with those of the present study have been recorded for bioceramic scaffolds in literature [ 42 , 43 ] , although usually degradation rate of bioceramics is evaluated by measuring mass loss after immersion in solutions like sbf or pbs due to their resemblance with physiological body fluids . in this study degradation of ceramic scaffolds was evaluated according to iso 10993 - 14 : 2009 which is more appropriate for testing materials in contact with fluids of different ph . the simulation test is a mild , common test used to evaluate the degradation rate of most ceramic materials under physiological ph and temperature similar to physiological body fluids , while the extreme test is related to the more aggressive environment to which a material can be exposed to in the oral cavity due to low ph . slight differences in scaffold 's porosity or structure through the fabrication process could explain such variation [ 42 , 45 ] . greater degradation values were reported in literature , only for significantly longer immersion period ( 1428 days ) [ 43 , 46 ] . lower degradation values were recorded after 3 days of immersion in tris buffer for wollastonite / tricalcium phosphate macroporous scaffolds , with significantly lower porosity ( 50% ) . the degradation rate of ca - p bioceramics is influenced by several parameters such as the sintering process , microstructure , crystallinity , and porosity . the porosity plays a dominant role in the degradation of bioceramics as it is related to high specific surface area . however the results of this study indicate that other mechanisms rather than porosity may be more crucial in determining the degradation of the scaffolds , such as composition and crystalline structure . ftir spectra of zna2 glass - ceramic scaffolds could not reveal any differentiation in their chemical composition even after 21 days of immersion in sbf solution , as shown in figure 6(a ) . this result may be attributed to the presence of bridging oxygen as shown by the strong peak at 796 cm , as already mentioned . on the contrary , cua2 bioactive scaffolds presented bioactive behavior according to ftir spectra ( figure 6(b ) ) . more specific , ftir spectra , after 10 days of immersion , revealed the formation of a weak double peak at 587 cm and 603 cm , which is attributed to the vibration of the p - o bond of the phosphate group . the high amount of wollastonite crystallized on the initial material could explain the delayed formation of apatite on the surface of cua2 glass - ceramic scaffolds . after 21 days of soaking in sbf solution , a stronger double peak at 587 cm and 603 cm was formed . additionally , at the same immersion time , the broad peak at 9001200 cm shifted towards ~1100 cm and became less wide . therefore , after 21 days of soaking in sbf there is a strong indication of the formation of apatite on the surface of the glass - ceramic scaffolds of the cua2 group . these findings are in accordance with xrd patterns ( figure 7 ) for both groups of glass - ceramic scaffolds . namely , zna2 samples did not show any compositional differentiation after 10 days of immersion in sbf solution , whereas cua2 patterns revealed a peak corresponding to apatite after 10 days of soaking . the effect of zinc incorporation on the structure of various bioactive glasses has resulted in different results concerning bioactivity depending on the microstructure and physicochemical properties of zn - doped glasses . although the acellular formation of calcium phosphate layer on the surface of bioactive silicate glasses doped with zn have been shown to occur after soaking in biological fluids [ 49 , 50 ] , other studies have shown that zn content reduces the overall leaching activity of the glass inhibiting the formation of the hca layer on its surface . reported a delayed formation of hca which was related to the slower degradation profile of the zn - doped bioactive glasses , in accordance with the results of this study . on the other hand , cu - doped 45s5 bg scaffolds exhibit high apatite forming ability , as proven by the rapid formation of a carbonated ha layer on their surface ( 3 days in sbf ) . hoppe et al . reported that cu addition ( up to 2.5wt% cuo ) had no effect on the reactivity of the undoped bg , as measured through immersion in sbf . fabricated sol - gel mg - based scaffolds with the foam replica technique and reported apatite formation on scaffolds sintered at 1350c after 9 days in sbf . as the authors in the current study used the same starting glass formulation , the incorporation of copper resulted in a slight delay of apatite formation , taking into consideration the lower crystallization temperature of the scaffolds . dpscs were able to attach and proliferate in both biomimetic scaffolds ( figures 8 and 9 ) . however , both mtt assay and sem analysis revealed a much better biological behavior of zna2 compared to the cua2 scaffolds . zna2 supported a statistically significant higher viability of dpscs compared to the cua2 scaffolds at all time points tested ( p < 0.01 ) . zna2 scaffolds showed an increase of cell viability / proliferation up to day 7 and decrease afterwards , which can be explained by the initiation of differentiation of dpscs inside the biomimetic microenvironment , which is usually accompanied by a cease in proliferation , as already shown in preliminary experiments with real - time pcr analysis and western blotting ( data under preparation ) . on the contrary cua2 scaffolds showed much lower od values compared to the zna2 scaffolds , with viability / proliferation increasing until day 3 and significantly decreasing afterwards . whether this inferior biological behavior of cua2 scaffolds is due to a very high release of cytotoxic concentrations of cu or any other elements needs further investigation . the results of the mtt assay were also in accordance with the results obtained by the sem analysis . cells grown inside the zna2 scaffolds were more densely seeded , with an atractoid , spindle - shaped morphology , indicative of proper attachment and high viability of cells within the scaffold . cells grown inside the cua2 scaffolds , on the other hand , were fewer and with a rather rounded morphology , indicative of poor attachment and potential cytotoxicity . zn - doped sol - gel derived glasses based on 58s have shown higher cellular viabilities than similar cu - doped glasses , in a recent study by bejarano et al . , although both were cytotoxic compared to undoped control 58s . the enhanced cell behavior recorded in the present study is probably attributed to a more stabilized zn - derived glass structure that restricted mass glass dissolution and ion release that could exert cytotoxic behavior . preliminary , unpublished data of the authors suggest that zna2 scaffolds combined with dpscs and growth / morphogenetic factors such as dentin matrix protein , dmp-1 , and bone morphogenetic protein , bmp-2 , promote odontogenic differentiation and dentin - like tissue formation . bioactive ceramic scaffolds , with adequate porosity , over 74% , and pore interconnectivity were produced by the foam replica technique . cu - doped mg - based scaffolds revealed apatite forming ability after 10 days immersion in sbf , while zn - doped mg - based scaffolds failed to develop apatite formation even after 21 days in sbf . differences in structure are responsible for the different degradation profile , mechanical behavior , and bioactivity of the synthesized scaffolds . despite failure to develop apatite zna2 scaffolds were proved very efficient to provide controlled degradation rate and a biomimetic environment for the long - term attachment and growth of dpscs ( up to 14 days ) , which makes them very promising for further research on their potential to induce odontogenic differentiation of dpscs and calcified dental tissue production for targeted dentin regeneration .
glass - ceramic scaffolds containing mg have shown recently the potential to enhance the proliferation , differentiation , and biomineralization of stem cells in vitro , property that makes them promising candidates for dental tissue regeneration . an additional property of a scaffold aimed at dental tissue regeneration is to protect the regeneration process against oral bacteria penetration . in this respect , novel bioactive scaffolds containing mg2 + and cu2 + or zn2 + , ions known for their antimicrobial properties , were synthesized by the foam replica technique and tested regarding their bioactive response in sbf , mechanical properties , degradation , and porosity . finally their ability to support the attachment and long - term proliferation of dental pulp stem cells ( dpscs ) was also evaluated . the results showed that conversely to their bioactive response in sbf solution , zn - doped scaffolds proved to respond adequately regarding their mechanical strength and to be efficient regarding their biological response , in comparison to cu - doped scaffolds , which makes them promising candidates for targeted dental stem cell odontogenic differentiation and calcified dental tissue engineering .
the moduli space of pairs @xmath0 with @xmath1 a complex connected smooth projective curve of genus @xmath2 and @xmath3 a nonzero abelian differential on @xmath1 , and denoted here by @xmath4 , comes with the structure of a deligne - mumford stack , but we will just regard it as an orbifold . the forgetful morphism @xmath5 exhibits @xmath4 as the complement of the zero section of the hodge bundle over @xmath6 . a partition of @xmath4 into suborbifolds is defined by looking at the multiplicities of the zeros of the abelian differential : for any numerical partition @xmath7 of @xmath8 , we have a subvariety @xmath9 which parameterizes the pairs @xmath0 for which the zero divisor @xmath10 of @xmath3 is of type @xmath11 . we call a _ stratum _ of @xmath4 a connected component of some @xmath12 ( nb : our terminology differs from that of @xcite ) . kontsevich and zorich @xcite characterized the strata of @xmath4 in rather simple terms . first consider the case when @xmath1 is hyperelliptic . then an effective divisor of degree @xmath8 on @xmath1 is canonical if and only if it is invariant under the hyperelliptic involution . so the type @xmath11 of such a divisor has the property that any odd integer appears in it an even number of times . there are two cases where the support of the canonical divisor is an orbit of the hyperelliptic involution : one is of type @xmath13 and the other is of type @xmath14 ( the two cases corresponding to a weierstra point resp . a pair of points ) . the authors show that these make up strata and denote them by @xmath15 and @xmath16 respectively . notice that this fully covers the case @xmath17 . they show that for @xmath18 , @xmath19 is a stratum unless @xmath20 and all the terms of @xmath11 are even . in that case the canonical divisor is twice the divisor of an ( effective ) theta characteristic , which for @xmath20 can be even or odd ( for @xmath21 it is necessarily odd , as there is no effective even theta characteristic ) . these loci are connected and hence define strata : @xmath22 and @xmath23 . this completes the kontsevich - zorich characterization of the strata . each stratum is known to have a ` linear ' structure : it comes with an atlas of holomorphic charts whose transition maps lie in @xmath24 , where @xmath25 is the dimension of the stratum . a chart of this atlas at @xmath0 is defined as follows . note that @xmath3 defines an element @xmath26\in h^1(c , z_\ab;\cc)$ ] , where @xmath10 denotes the zero locus consisting of @xmath27 distinct points . if we put @xmath28 and choose an isomorphism @xmath29 , then varying @xmath0 in a small neighborhood in its stratum makes the image of @xmath26 $ ] vary in @xmath30 . this yields a @xmath30-valued chart . in particular @xmath31 . since every connected stratum @xmath32 of @xmath4 is invariant under scalar multiplication it defines a suborbifold @xmath33 in the @xmath34-orbifold bundle @xmath35 over @xmath6 . such a projectivized stratum parameterizes pairs @xmath36 with @xmath1 a smooth projective curve and @xmath37 a positive canonical divisor on @xmath1 with prescribed multiplicities . moreover , @xmath32 has a contractible orbifold universal cover if and only if @xmath33 has : in this case , the orbifold fundamental group of @xmath33 is the quotient of the orbifold fundamental group of @xmath32 by an infinite cyclic central subgroup . the somewhat technical price to pay for working with @xmath33 is that over the hyperelliptic locus we have to deal with @xmath38-gerbes . since @xmath32 has a linear structure , @xmath39 has a projective structure ( i.e. , it has a holomorphic atlas which takes values in @xmath40 such that the transition maps lie in a projective linear group ) . the topology of the hyperelliptic strata is familiar and although a bit subtle , essentially well understood . consider an affine plane curve @xmath41 with equation @xmath42 where the @xmath43 s are pairwise distinct . a projective curve @xmath44 is obtained by adding a point @xmath45 at infinity and @xmath46 extends over @xmath44 as an abelian differential @xmath47 with a unique zero at infinity . notice that @xmath47 naturally defines a nonzero element in @xmath48 . performing the above construction in families over @xmath49 we obtain a diagram @xmath50^f & \ccal^\circ\ar@{_(->}[l]\ar@{^(->}[r ] & \rcal_{2g+1}\times \aa^2 \ar[lld ] \\ \rcal_{2g+1 } \ar@/^1pc/[u]^\sigma } \ ] ] where @xmath51 is a smooth projective curve with a section @xmath52 . moreover , we also obtain a @xmath53 that vanishes along the image of @xmath52 of order @xmath8 and so a nowhere - zero section of @xmath54 over @xmath55 . the @xmath56-action on @xmath55 defined as @xmath57 lifts on @xmath58 as @xmath59 preserving @xmath60 and @xmath52 . notice that @xmath61 yields the hyperelliptic involution . the induced action on @xmath62 is @xmath63 , and so @xmath64 is isomorphic to @xmath65 if and only if @xmath66 with @xmath67 . moreover , the action of @xmath68 on @xmath55 that permutes the components of @xmath69 commutes with the @xmath56-action and so we obtain an isomorphism of orbifolds @xmath70^{\qquad\sim } & & \hcal^{hyp}(2g-2 ) } \ ] ] now , @xmath71 is a classifying space for the braid group @xmath72 on @xmath73 strands . hence @xmath74 is an orbifold classifying space for a group that is an extension of @xmath75 by @xmath72 . if we are interested in projective classes of abelian differentials , then we obtain @xmath76^{\qquad\qquad\sim } & & \pp\hcal^{hyp}(2g-2 ) } \ ] ] and so @xmath77 has a contractible orbifold universal cover and its orbifold fundamental group is a hyperelliptic mapping class group , namely the centralizer in the mapping class group of a hyperelliptic involution @xmath78 of a pointed genus @xmath79 surface ( which preserves the point ) and that the orbifold universal cover is contractible . similarly for @xmath80 , we consider affine plane curves @xmath81 of equation @xmath82 together with the differential @xmath83 . if @xmath44 is the smooth completion of @xmath81 obtained by adding the points at infinity @xmath84 and @xmath85 , then @xmath47 naturally determines a nonzero element in @xmath86 . implementing the above construction in families yields a smooth curve @xmath87 together with a divisor @xmath88 that projects tale @xmath89 onto @xmath90 , a @xmath91 that vanishes of order @xmath92 along @xmath88 and a nowhere - zero section of @xmath93 . a @xmath56-action can be defined on @xmath94 as @xmath95 and the induced action on @xmath62 is @xmath96 . we also have the obvious action of @xmath97 in this family ( which just permutes the @xmath43 s ) and the involution @xmath78 which sends @xmath98 to @xmath99 . these three actions commute , so that we have one of @xmath100 . the stabilizer of @xmath101 is @xmath102 and it is easy to see that any isomorphism @xmath103 is the restriction of an element of this stabilizer . so we obtain the isomorphism of orbifolds @xmath104^{\quad\sim } & & \hcal^{hyp}(g-1,g-1 ) } \ ] ] this makes @xmath80 an orbifold classifying space of an extension of @xmath105 by @xmath106 . it also shows that the orbifold fundamental group of @xmath107 is just a hyperelliptic mapping class group ( to be precise , it is the centralizer in the full mapping class group of a hyperelliptic involution of a twice pointed genus @xmath79 surface which exchanges the points ) and that the orbifold universal cover is contractible . in their preprint @xcite kontsevich and zorich conjecture that something similar is true in general , namely that each projectivized stratum always has a contractible orbifold universal cover and that its orbifold fundamental group is commensurable with some mapping class group . in this paper we give rather precise descriptions of all the strata in genus 3 . this enables us to find a presentation of their orbifold fundamental group , at least in principle : we do this for all the strata , except for the open stratum @xmath108 , where it gets unwieldy , and to make for these strata the kontsevich - zorich conjecture so explicit that it acquires more of a topological flavor . concretely , we show that the nonhyperelliptic strata in genus 3 can be understood as parameterizing del pezzo surfaces of degree two or one endowed with an anticanonical divisor of a given type and describe these in turn in terms of combinatorial ( root ) data . such moduli spaces have been investigated by one of us before . it turns out that they can be given in a somewhat similar spirit as the hyperelliptic strata : some orbifold cover appears as the complement of a locally finite arrangement in a domain and the in principle their fundamental group can be computed . for instance , for @xmath109 resp . @xmath110 we get the discriminant complement of the root system of type @xmath111 resp . its fundamental group is the artin group of that type and a highly nontrivial theorem of deligne @xcite asserts that this complement has indeed a contractible universal cover . but in the other cases this seems difficult to establish . questions of that kind are reminiscent , and indeed overlap , with the arnold - thom conjecture which states that the discriminant complement of the universal deformation of an an isolated hypersurface singularity is a @xmath113 . they are still the subject of current research @xcite . we do not know how to make the commensurability conjecture of kontsevich and zorich precise . our results seem to indicate that the open stratum @xmath114 has an orbifold fundamental group which may _ not _ be commensurable with a central extension of the mapping class group of the punctured genus 3 curve . in fact , for none of the strata described here , we were able to characterize their orbifold fundamental group as a kind of a mapping class group . e.l . wishes to thank the mathematical sciences research institute and the tsinghua mathematics department for support and hospitality during the period part of this work was done . g.m . would like to thank the park city mathematical institute for the hospitality in july 2011 . let @xmath1 be a nonhyperelliptic nonsingular curve of genus @xmath115 . the canonical system on @xmath1 embeds in a projective plane @xmath116 . a double cover @xmath117 of this plane which totally ramifies over @xmath1 is unique up to the obvious involution . the covering variety @xmath118 is a del pezzo surface of degree 2 , which here amounts to saying that the anticanonical system on @xmath118 is ample and is given by the morphism @xmath119 : any effective anticanonical divisor on @xmath118 is the pull - back of a line in @xmath116 . every effective anticanonical divisor on @xmath118 has arithmetic genus one ( this is also clear from the way we defined @xmath118 ) . if @xmath120 is a double tangent of @xmath1 , then its preimage in @xmath118 consists of two exceptional curves ( an _ exceptional curve _ is a smooth genus zero curve with self - intersection @xmath121 ) which intersect each other with intersection number @xmath122 . since there are 28 bitangents we get @xmath123 exceptional curves and these are in fact all of them . if we select @xmath124 such exceptional curves that are pairwise disjoint , then their contraction yields a copy of @xmath125 and the anticanonical system is then realized as the system of cubics passing through the 7 image points of this @xmath125 . there are however many ways of picking 7 pairwise disjoint copies and the best way to come to terms with this is to invoke an associated symmetry group , which is a weyl group of type @xmath111 . let us make this precise . the natural map @xmath126 is an isomorphism . the latter is free of rank 8 and its intersection pairing can be diagonalized with on the diagonal a @xmath127 followed by seven @xmath121 s . if @xmath128 stands for the anticanonical class , then it is clear that @xmath129 . so the orthogonal complement of @xmath130 in @xmath131 , denoted here by @xmath132 , is negative definite . a _ root _ is an element @xmath133 with @xmath134 . associated to a root @xmath135 is a reflection @xmath136 in @xmath131 , given by @xmath137 , which fixes @xmath130 and preserves the intersection pairing . these reflections generate a weyl group @xmath138 of type @xmath111 so that the roots make up a root system @xmath139 of the same type . it is known that the classes of the exceptional curves generate @xmath131 and that the roots generate @xmath132 . a root can be represented by the difference of two disjoint exceptional curves , although not uniquely so . the weyl group @xmath138 is the full stabilizer of @xmath130 in the orthogonal group of @xmath131 . the involution of @xmath118 preserves @xmath130 and acts as minus the identity in @xmath132 , hence appears here as the central element of @xmath138 . but the other nontrivial elements of @xmath138 are usually not induced by an automorphism of @xmath118 . let @xmath37 be a positive canonical divisor on @xmath1 . then @xmath37 is the trace of a line @xmath140 on @xmath1 and @xmath141 is an anticanonical divisor on @xmath118 . as we noted , the latter is of arithmetic genus one : if @xmath37 is general ( of type @xmath142 ) , then @xmath143 is smooth and in the other cases @xmath143 is a nodal curve ( @xmath37 is of type @xmath144 ) , a bigon ( type @xmath145 in the kodaira classification and @xmath37 is of type @xmath146 ) , a cuspidal curve ( type @xmath147 in the kodaira classification and @xmath37 is of type @xmath148 ) or two smooth rational curves meeting in a point with multiplicity 2 ( type @xmath149 in the kodaira classification and @xmath37 is of type @xmath150 ) . we regard @xmath143 as a genus one curve endowed with a polarization of degree 2 . the group @xmath151 of isomorphism classes of line bundles on @xmath143 has as its identity component @xmath152 an elliptic curve , is isomorphic to @xmath153 or is the additive group @xmath154 , according to whether @xmath37 is reduced , has a point of multiplicity @xmath122 , or has a point of multiplicity @xmath155 . the orthogonal complement in @xmath131 of the classes of the irreducible components of @xmath143 , denoted here by @xmath156 , is generated by the roots contained in it , so that these roots make up a root subsystem @xmath157 . we have only two cases : for @xmath143 irreducible , we have of course @xmath158 and otherwise ( when @xmath143 has two irreducible components interchanged by @xmath159 ) , @xmath160 is of type @xmath112 ( see table 1 ) . the natural homomorphism @xmath161 has an evident restriction @xmath162 it plays a central role in what follows . let us first observe that no root @xmath163 lies in the kernel of @xmath164 . for such a root @xmath135 can be represented by a difference @xmath165 of disjoint exceptional curves @xmath166 which meet the _ same _ component of @xmath167 , in @xmath45 resp . @xmath168 , say . then clearly , @xmath169 represents @xmath170 and since @xmath171 , it is a nonzero element of @xmath152 . + [ cols="^,^,^ " , ] we now view @xmath164 as an element of @xmath172 . this last group is a weight lattice of type @xmath112 or @xmath111 tensored with either an elliptic curve , a copy of @xmath173 or a copy of @xmath154 ( which is like a six- or sevenfold power of the latter but with a weyl group symmetry built in ) . its isomorphism type is a complete invariant of the pair @xmath174 ( and hence of the pair @xmath36 ) . to be more concrete , let us identify @xmath175 with a fixed root system @xmath176 of type @xmath112 or @xmath111 . two such identifications differ by an element of the automorphism group @xmath177 of @xmath176 , which is @xmath178 in the @xmath112 case and @xmath179 in the @xmath111 case . we also identify @xmath152 with a fixed group @xmath180 , which is either an elliptic curve , or the multiplicative group @xmath173 or the additive group @xmath154 . two such identifications differ by an automorphism of @xmath180 . notice that @xmath181 equals @xmath182 for @xmath180 a generic elliptic curve or @xmath183 and is equal to @xmath173 when @xmath184 . so if we denote by @xmath185 the ( root ) lattice spanned by @xmath176 , and by @xmath186 homomorphisms with no root in their kernel , then our @xmath164 defines an element of @xmath187 for @xmath176 and @xmath180 as listed . this construction also makes sense for families of elliptic curves . in fact , if @xmath188 is the universal elliptic curve ( an orbifold ) , then we can form @xmath189 . let us write @xmath190 for the moduli stack of @xmath191-element subsets of @xmath192 up to projective equivalence , in other words , @xmath193 . there is an evident @xmath38-gerbe @xmath194 ( a ` @xmath195-fibration ' ) , that makes @xmath189 fiber over @xmath190 . [ thm : non - hyperelliptic ] the map @xmath196 induces orbifold isomorphisms @xmath197 here @xmath198 denotes the locus in @xmath199 for which the underlying curve is hyperelliptic . the main result of deligne in @xcite implies that any variety of the form @xmath200 is an orbifold classifying space of its orbifold fundamental group . if @xmath176 has the property that its automorphism group is @xmath201 or @xmath179 ( which is the case when it is of type @xmath202 or @xmath203 ) , then the orbifold fundamental group in question equals the quotient of the artin group of type @xmath179 by its natural ( infinite cyclic ) central subgroup . hence we find : [ cor : ] the stratum @xmath204 resp . @xmath205 is an orbifold classifying space for the artin group of type @xmath111 resp . @xmath112 modulo its natural ( infinite cyclic ) central subgroup . but we do not know how to characterize any of these groups as a kind a mapping class group . the strata corresponding to @xmath206 contain both non - hyperelliptic and hyperelliptic curves . thus , we must know how adding @xmath207 to @xmath208 can be expressed in terms of the right hand side in theorem [ thm : non - hyperelliptic ] . let us first give each of the @xmath207 a description in the same spirit as the varieties we dealt with . + let us first observe that the hyperelliptic involution gives each @xmath207 the structure of a @xmath38-gerbe . the following proposition identifies the base : [ prop : hypergerbe ] the hyperelliptic involution yields natural @xmath38-gerbes @xmath209 where we note that @xmath210 is a double cover . the loci in question are the moduli stacks for the pairs @xmath36 for which @xmath1 is a hyperelliptic genus three curve and @xmath211 is the union of two distinct orbits under the hyperelliptic involution . the three cases correspond to having 0,1 , or 2 weierstra points in @xmath211 . if we divide out by the hyperelliptic involution , we get a copy of @xmath192 . we make the identification in such a manner that the @xmath212 , where in case @xmath213 we let @xmath214 be the image of the weierstra point . this identifies the stratum @xmath215 , @xmath216 , @xmath217 modulo the hyperelliptic involution with the configuration space of subsets of @xmath153 of 8 resp . 7 resp . 6 elements , modulo the obvious @xmath173-action and , in the first and the last case , also modulo the involution . these are easily seen to be as asserted . in order to understand how these loci lie in their strata , we need to have a unified picture that includes both non - hyperelliptic and hyperelliptic curves . while the anti - canonical model is adequate to discuss the case of a non - hyperelliptic curve , the bi - anti - canonical model is more suited to analyze what happens near the hyperelliptic locus . the degeneration of the del pezzo surfaces using the anti - canonical model only was analyzed in @xcite . this section is inspired by similar ideas occurring in @xcite . given a curve @xmath1 of genus @xmath115 , then the canonical map @xmath218 is an embedding in a projective plane unless @xmath1 is hyperelliptic , in which case it factors through the hyperelliptic involution ( which we will always denote by @xmath78 ) and has a conic as image . on the other hand , the bicanonical map @xmath219 is always an embedding in a 5-dimensional projective space and this allows us to identify @xmath1 with its image in @xmath220 . let @xmath221 be the veronese embedding . the multiplication map @xmath222 induces a rational map @xmath223 : p'_c\dashrightarrow \check\pp(\sym^2 h^0(c,\can_c))$ ] and @xmath1 will always lie on @xmath224^{-1}j(p_c)$ ] . it is therefore of interest to determine what @xmath225 is like . for @xmath1 non - hyperelliptic the map @xmath226 is an isomorphism . hence so is @xmath223 $ ] and this shows that @xmath225 is a veronese surface and naturally isomorphic to @xmath116 . we also find that this isomorphism takes @xmath227 to @xmath228 . thus , @xmath229 embeds @xmath1 in @xmath220 as the intersection of @xmath225 with a quadric : @xmath228 appears as a divisor of @xmath230 . the situation is somewhat more complicated for @xmath1 hyperelliptic . the hyperelliptic involution @xmath78 acts as @xmath121 in @xmath231 and hence trivially in @xmath232 . but it acts in @xmath233 as reflection . the image of @xmath226 is the full fixed point hyperplane of this reflection and so @xmath226 has @xmath127-dimensional kernel and cokernel . the kernel of @xmath226 is of course spanned by an element of @xmath232 , which , when viewed as a quadratic form on @xmath234 , defines the image of @xmath235 ( a conic in @xmath116 ) . and so the hyperplane @xmath236 defined by this kernel has the property that @xmath237 . it also follows that the fixed point set of @xmath78 in @xmath220 consists of a hyperplane @xmath238 and a singleton @xmath239 , that @xmath223 $ ] establishes an isomorphism @xmath240 ( we will therefore identify the two ) and that @xmath223:p'_c\rightarrow\check\pp(\sym^2 h^0(c,\can_{c}))$ ] is the linear projection with center @xmath241 onto @xmath238 followed by the embedding @xmath242 . this implies that @xmath225 is the cone with vertex @xmath241 and base the image of @xmath243 . the image @xmath228 lies in the smooth part of the cone @xmath225 and ( again ) appears as a divisor of @xmath230 . notice that the involution @xmath78 acts on each ray of @xmath225 as the unique nontrivial involution that fixes its intersection with @xmath238 and the vertex @xmath241 . moreover , the linear projection maps @xmath228 onto as a double cover branched along an 8-element subset @xmath244 , whose two sheets are exchanged by @xmath78 . incidentally , we remark that there are two distinct types of rays @xmath245 : * an _ ordinary ray _ @xmath246 : one that meets @xmath228 transversely in two points , so that @xmath78 acts nontrivially on @xmath247 ; * a _ weierstra ray _ @xmath248 : one that is tangent to @xmath228 at a point @xmath249 . we also observe that the minimal resolution of the vertex of @xmath225 has as its exceptional set a rational curve of self - intersection @xmath250 . the complement of the vertex in @xmath225 is isomorphic to the total space of the line bundle @xmath251 over @xmath252 . in other words , @xmath225 is obtained from a segre - hirzebruch surface @xmath253 by blowing down the @xmath254-section . thus , @xmath225 is a simply connected rational homology manifold with the homology of a complex projective plane and one can directly check that the restriction map @xmath255 is an isomorphism . indeed , the @xmath254-singularity of the cone @xmath225 is homogeneous and @xmath256 can be obtained as the quotient of an affine plane @xmath257 by the diagonal action of @xmath258 . the local picard group of a @xmath254-singularity is cyclic of order @xmath191 with generator a ray @xmath246 and @xmath259 is a hyperplane section of @xmath225 and so locally principal . it follows that @xmath260 is generated by the class of @xmath259 , and that since @xmath261 , it follows that @xmath262 . clearly , @xmath263 . conversely , the pair @xmath264 is easily reconstructed up to isomorphism from an 8-element subset @xmath265 of a projective line @xmath192 , for the double cover of @xmath192 ramified along @xmath265 sits naturally in the total space of @xmath251 and that total space can be identified with the complement of the vertex of a cone as above . _ notation . _ in what follows , we will always identify a curve @xmath1 with its image through the bicanonical embedding . for a hyperelliptic @xmath1 , we will write @xmath266 for the rational curve @xmath267 sitting inside @xmath225 . let @xmath268 be hyperelliptic of genus 3 . it has a semi - universal deformation whose base is a smooth germ @xmath269 of dimension 6 with @xmath270 naturally identified with the dual of @xmath271 . the universal property implies that the hyperelliptic involution @xmath78 extends to this universal deformation . the identification @xmath272 is @xmath78-equivariant . as we have seen @xmath78 acts as a reflection on @xmath271 and so @xmath78 also acts as such on @xmath270 . the action of @xmath78 on @xmath269 can be linearized in the sense that we can choose coordinates for @xmath269 in terms of which @xmath78 is a reflection . the @xmath273-eigenspace then parametrizes hyperelliptic deformations . but our interest concerns rather the @xmath274-eigenspace , or more invariantly put , a transversal slice to the hyperelliptic locus invariant under @xmath78 ( it is not unique ) . in other words , we consider a one - parameter deformation @xmath275 of @xmath268 such that @xmath276 is non - hyperelliptic for @xmath277 , that the kodaira - spencer map is nonzero at @xmath278 and that the hyperelliptic involution @xmath78 extends to our family and takes @xmath276 to @xmath279 . the above construction carries over in families and we obtain a factorization of the relative bicanonical embedding over @xmath280 @xmath281 through a surface @xmath282 over @xmath280 with central fiber @xmath283 a cone over a rational rational normal curve and general fiber a veronese surface and we obtain @xmath284 as divisor of a section @xmath285 of @xmath286 . we incidentally notice that @xmath287 deforms to the complement of a hyperplane section of @xmath288 , and so the milnor fiber of this degeneration has the homotopy type of the complement of a conic in @xmath125 , that is , of a real projective plane . we note that @xmath289 is generated by @xmath290 . but on @xmath288 , @xmath291 , @xmath292 represents twice the generator and so the image of the specialization map @xmath293 has index two . this corresponds ( dually ) to the fact that a line on the generic fiber of @xmath294 ( that is , a line in @xmath295 under the image of veronese map ) may only extend as a weil divisor with specialization to the sum of two rays ( only four times a ray is a divisor of @xmath292 ) . for example , each bitangent of @xmath296 specializes to the sum of two weierstra rays @xmath297 and this establishes a bijection between the 28 bitangents of @xmath296 and the collection of all 2-element subsets of @xmath265 . we deduce that the monodromy action of @xmath298 on the cohomology of the general fiber of @xmath294 is trivial . indeed , the bundle @xmath299 is trivial and @xmath300 is an isomorphism for all @xmath301 . for essentially the same reason , the `` half - monodromy '' action of @xmath78 : @xmath302 is ( after we make an identification @xmath303 via a path in @xmath304 ) the also trivial . the action of @xmath78 on the family @xmath305 and so on the total space of the vector bundle @xmath306 induces an action on the total space of @xmath290 , which in particular fixes the fibers over @xmath307 . it acts as minus the identity on the fiber over @xmath241 and as plus the identity on its restriction to @xmath308 . hence , upon replacing @xmath285 by @xmath309 , we may assume that @xmath285 is @xmath78-invariant . as @xmath285 is a divisor for @xmath284 , we can construct the double cover @xmath310 branched over @xmath284 inside the total space of @xmath290 as the set of points whose square is a value of @xmath285 . by construction it comes with an action of @xmath78 . if we identify @xmath282 with the zero section of this total space , then we see that @xmath284 is also the ramification locus of @xmath119 . we denote by @xmath159 the natural involution of @xmath311 . we remark that the actions of @xmath159 and @xmath78 commute . for @xmath312 , @xmath313 is clearly isomorphic to the del pezzo surface @xmath314 , whereas @xmath315 has two isolated singular points @xmath316 mapping to the vertex @xmath241 of @xmath283 . notice that besides the inclusion @xmath317 there is another copy of @xmath268 embedded inside @xmath315 , namely preimage @xmath318 and that the two meet each other in the 8 weierstra points . the involution @xmath159 fixes @xmath268 pointwise and acts as the hyperelliptic involution on @xmath318 , whereas @xmath78 fixes @xmath318 pointwise and acts nontrivially on @xmath268 . denote by @xmath319 be the preimage inside @xmath315 of a ray @xmath320 . * if @xmath246 is an ordinary ray , then @xmath319 is a smooth rational curve that doubly covers @xmath246 . there are six special points on @xmath319 : the ramification points @xmath321 , the singularities @xmath316 of @xmath315 and the preimages @xmath322 of @xmath323 . the involutions @xmath159 and @xmath78 on @xmath319 are characterized by the property that their fixed point pairs are @xmath324 and @xmath325 respectively ( so @xmath159 , @xmath78 and @xmath326 permute the 6 points respectively as @xmath327 , @xmath328 and @xmath329 . * if @xmath330 is a weierstra ray through @xmath331 , then @xmath332 , where @xmath333 is a smooth rational curve passing through @xmath334 and isomorphically mapping to @xmath330 and @xmath335 ( @xmath336 an ordinary double point of @xmath337 ) . both @xmath159 and @xmath78 act on @xmath337 by exchanging @xmath338 and @xmath339 and fixing @xmath336 , and so exchanging @xmath340 and @xmath341 ; but their action is different : in fact , @xmath326 preserves each component and acts on @xmath333 as the only nontrivial involution that fixes @xmath334 and @xmath336 . the variety @xmath315 is a rational homology manifold too , and indeed the specialization map @xmath342 is an isomorphism , so that poincar duality holds and all divisors are @xmath343-cartier . the intersection pairing of the liftings of weierstra rays satisfy @xmath344 and @xmath345 for every @xmath331 and that for @xmath346 distinct , @xmath347 and @xmath348 . so @xmath349 is a cartier divisor of self - intersection @xmath350 , whereas @xmath351 is only a weil divisor and has self - intersection @xmath121 . as anticipated before , the 28 double tangents appear in the limit in the central fiber of @xmath352 as the @xmath353 couple of weierstra rays . the corresponding pairs of exceptional curves on the general fiber have a decent limit on the central fiber of @xmath354 and this limit can be described as follows . for every @xmath122-element subset @xmath355 , denote by @xmath356 resp . by @xmath357 the weil divisor @xmath358 resp . @xmath359 inside @xmath315 . this describes the 56 limits of the exceptional curve on the general fiber : we get a flat family @xmath360 whose general fiber is an exceptional curve on a del pezzo surface of degree 2 . notice that the involutions @xmath159 and @xmath78 interchange @xmath361 and @xmath362 . the intersection numbers of these exceptional classes , insofar they are not self - intersections , take their values in @xmath363 and we have ( compare @xcite , lemma ( 6.4 ) for a different model ) : * if @xmath364 is a singleton , then @xmath365 and @xmath366 , * if @xmath367 , then @xmath368 and @xmath369 and * @xmath370 . since the picard group of the general fiber of @xmath371 is spanned by the exceptional classes , we see how that group specializes in the central fiber . we also see that on the central fiber , roots are still represented as differences of disjoint exceptional curves . notice that this construction leaves a trace on the relative picard group of the generic fiber @xmath372 ( the superscript @xmath373 refers to restriction over @xmath304 ) , for it divides the exceptional curves of the generic fiber in two subsets that are interchanged by the involution @xmath159 . these are in fact separated by the character @xmath374 which takes the value @xmath375 on @xmath376 . in fact , we may identify @xmath377 with the kernel of @xmath378 . we can be more explicit if @xmath372 is given as a projective plane @xmath379 blown up in @xmath124 numbered @xmath304-valued points . this yields another basis of @xmath380 , namely @xmath381 , where @xmath382 is the preimage of the class of a line in @xmath379 and @xmath383 denotes the class of the exceptional divisor over the @xmath384-th point . then @xmath385 is the anticanonical class and we can number the elements of @xmath265 : @xmath386 in such a manner that @xmath387 the elements @xmath388 and @xmath389 make up a root basis of @xmath390 . the roots in @xmath391 are @xmath392 , @xmath393 and @xmath394 , @xmath395 . this is in fact a root subsystem of type @xmath396 for which @xmath397 is a root basis . we rephrase this for purposes of record in the following . any root @xmath398 can be written either as a difference @xmath399 ( the roots in @xmath400 ) or as @xmath401 ( the remaining ones ) , depending on whether @xmath364 is a singleton or empty . the roots of the first type are precisely the ones that lie in the image of @xmath377 and make up a root subsystem @xmath402 of @xmath390 of type @xmath396 . moreover , the permutation action of @xmath403 on the collection of @xmath404 s defines an isomorphism of @xmath403 onto the weyl group of @xmath402 and identifies @xmath405 with the @xmath406-stabilizer of @xmath400 . both @xmath78 and @xmath159 act on @xmath390 as minus the identity . now let be given a family of conics @xmath407 degenerating into @xmath408 . there are three cases : * @xmath409 and @xmath410 are ordinary rays , accounting for @xmath411 , * @xmath409 is ordinary and @xmath410 is weierstra , accounting for @xmath412 , * both @xmath409 and @xmath410 are weierstra rays , accounting for @xmath413 . we think of @xmath414 as defining a relative canonical divisor @xmath415 on the degenerating family @xmath305 and we need to understand how the basic invariant @xmath416 specializes over @xmath417 . this is the subject of the following two sections . this concerns the stratum @xmath418 . we focus on the limiting behavior near the hyperelliptic locus and so we assume that we are in the situation of section [ sect : bianti ] and that @xmath419 is the sum of two ordinary rays @xmath409 and @xmath410 . then the preimage of @xmath419 in @xmath315 ( denote it @xmath420 ) consists two smooth rational components @xmath421 and @xmath422 that meet at @xmath338 and @xmath339 . this is the central fiber of a genus one fibration @xmath423 with smooth general fiber : it is a degeneration of type @xmath145 ; in particular , the central fiber is of multiplicative type . the @xmath424-function of such a degeneration has a pole of order two at @xmath417 . in fact , the involution @xmath78 nontrivially acts on the family @xmath425 interchanging the fibers with the same @xmath424-invariant . [ lemma : specialize ] let @xmath426 be a root . then @xmath427 specializes as an element in the identity component of @xmath428 if and only if @xmath429 . let @xmath430 be obtained by blowing up @xmath431 at @xmath338 and @xmath339 . then @xmath432 is the union of a double cover @xmath433 of a segre - hirzebruch surface and two copies @xmath434 of @xmath435 glued along the two @xmath254-sections @xmath436 of @xmath433 . denote by @xmath437 the strict transforms of @xmath438 and by @xmath439 the preimage of @xmath440 inside @xmath441 . then its closure @xmath442 is a degeneration of type @xmath443 as @xmath444 is the union of @xmath445 , @xmath446 , @xmath447 and @xmath448 . if @xmath449 is the strict transform of @xmath450 for some @xmath331 , then @xmath449 meets @xmath444 in the smooth locus of @xmath436 . hence , if @xmath451 denotes the strict transform of @xmath404 , then the locus @xmath452 defines a relative divisor @xmath453 on @xmath454 of degree @xmath122 . let @xmath426 be represented by @xmath399 resp . @xmath401 . then @xmath455 specializes to @xmath456 resp . @xmath457 on @xmath444 . this specialization lies in the identity component of @xmath458 precisely if @xmath459 . the conclusion follows because the pull - back induces an isomorphism between the identity components of @xmath458 and @xmath428 . this describes in a rather concrete manner how the restriction homomorphism @xmath460 specializes over the central fiber , for we also find that the limit @xmath461 exists precisely if @xmath429 . indeed , if @xmath462 , then after identifying @xmath463 with @xmath173 , the value of @xmath461 tends to @xmath464 or @xmath214 ( depending on the identification ) . the involutions @xmath159 and @xmath78 act on @xmath463 as the inversion and @xmath465 . this gives rise to the following extension of @xmath466 . we begin with what may be considered as a reconstruction of @xmath467 . we start out with the algebraic torus @xmath468 and the automorphism @xmath469 of @xmath470 defined by @xmath471 . this automorphism preserves the open subset @xmath472 and generates a group @xmath473 that s acts properly and freely on @xmath474 . so the orbit space @xmath475 is a complex manifold of dimension two . it maps homomorphically to @xmath304 and this realizes @xmath475 as the tate curve over @xmath304 . we construct an extension @xmath476 of @xmath475 over @xmath280 by means of a familiar construction from toric geometry . the coordinates give the lattice @xmath477 of one parameter subgroups of @xmath478 a natural basis @xmath479 . the rays in @xmath480 spanned by the vectors @xmath481 with @xmath482 , and the sectors spanned by two successive rays define a partial polyhedral decomposition @xmath483 of @xmath480 . this decomposition is clearly invariant under @xmath469 . the associated torus embedding @xmath484 is a complex manifold of dimension two . let @xmath485 be the interior of the closure of @xmath474 in @xmath486 . then @xmath473 acts properly and freely on @xmath487 . we let @xmath476 be the orbit space of @xmath487 with respect to the subgroup @xmath488 . this is also a complex manifold and it is the total space of a degeneration @xmath489 of curves of genus @xmath127 of type @xmath145 . we denote by @xmath490 ( resp . by @xmath491 ) the complement of the two punctual strata in the central fiber inside @xmath492 ( resp . inside @xmath476 ) . the section @xmath493 $ ] of @xmath494 makes it into a relative abelian variety , which we denote by @xmath495 . we remark that @xmath496 . the automorphism @xmath469 induces in @xmath489 an order two translation . we have also natural commuting involutions @xmath159 and @xmath78 on @xmath489 , which are defined as @xmath497=[z_1,z_2^{-1}]$ ] and @xmath498=[-z_1,-z_2^{-1}]$ ] , so that the `` half - monodromy '' acts on @xmath499 as @xmath500\mapsto [ -z_2^{-1}]$ ] . the induced actions of @xmath159 and @xmath78 on @xmath495 , given by @xmath497=[z_1,z_2^{-1}]$ ] and @xmath498=[-z_1,z_2^{-1}]$ ] , generate the automorphism group of @xmath495 . we incidentally notice that the `` half - monodromy '' acts on @xmath501 as the inverse ( for the group operation on @xmath501 ) . if @xmath502 denotes the group of sections of @xmath495 , then we have a natural surjective homomorphism @xmath503 let @xmath176 be a fixed root system of type @xmath111 . the group of homomorphisms @xmath504 is represented by a @xmath280-scheme that we shall denote by @xmath505 . concretely , a basis @xmath506 of @xmath185 identifies this @xmath280-scheme with a 7-fold fiber product @xmath507 . its central fiber has @xmath508 connected components and these are canonically labeled by the group @xmath509 . it follows from our discussion of the hyperelliptic limit that we must consider only some of these components , namely those that correspond to @xmath510 for which @xmath511 has as kernel a root sublattice of type @xmath396 . at this point we recall that the root subsystems of type @xmath396 of @xmath176 are transitively permuted by the weyl group @xmath179 and that the sublattice spanned by such a subsystem has index 2 in @xmath185 . let us denote by @xmath512 the locus in @xmath505 defined by the @xmath510 with the above property . this subset is open and @xmath179-invariant . by the preceding remark , @xmath179 is transitive on the connected components of the central fiber , the stabilizer of a connected component being a weyl group of type @xmath396 times the center @xmath513 of @xmath179 . removing the fixed point loci of reflections yields an open subset @xmath514 and we then put @xmath515 if we fix a root subsystem @xmath516 of type @xmath396 , then we see that the central fiber of @xmath517 is identified with the component of @xmath518 that maps @xmath519 to @xmath520 . restriction to @xmath519 identifies this in turn with @xmath521 . we also observe that @xmath522 maps to the quotient of @xmath304 by the involution @xmath523 . so if we ignore the orbifold structure , then we have attached a copy of @xmath524 to @xmath466 . now notice that the orbifold @xmath524 is the moduli space of @xmath525-element subsets of @xmath173 given up a common scalar and up to a ( common ) inversion . this is also the moduli space of 10-element subsets of a projective line endowed with a distinguished subset of 2 elements . if we pass to double covers ramifying over the remaining 8 points , we see that this is nothing but @xmath526 . with this interpretation , the added locus is even identified with @xmath526 as an orbifold . in order to make the construction global it is best to pass to a level two structure : consider the universal elliptic curve with a level two structure @xmath527/\mcal_{1,1}[2]$ ] ( a deligne - mumford stack ) . it comes with a @xmath528-action . we extend this to across the completed modular curve @xmath529/\overline{\mcal}_{1,1}[2]$ ] with curve of type @xmath145 added as singular fibers . denote by @xmath530/\overline{\mcal}_{1,1}[2]$ ] the associated abelian stack and define the stack @xmath531/\overline{\mcal}_{1,1}[2])$ ] in an evident manner . we then put @xmath532/\overline{\mcal}_{1,1}[2])^\circ/ { \operatorname{sl}}(2 , \zz/2).\ ] ] the right hand side contains @xmath533 , where the point added to @xmath534 ( the cusp ) is represented by a divisor on @xmath192 which is twice a positive reduced divisor of degree two . its complement is a @xmath38-gerbe over @xmath535 and we conclude : [ thm:1,1,1,1 ] we have a natural isomorphism @xmath536 over @xmath534 which identifies @xmath537 with the fiber over the cusp ( which , as we noted , has the structure of a @xmath38-gerbe over @xmath535 ) . this theorem gives us , at least in principle , access to the homotopy type of @xmath418 , although we admit that this may be hard in practice . a computation of its orbifold fundamental group looks feasible , however . we return to the limiting discussion in section [ sect : bianti ] . but now we assume here that @xmath539 is tangent to @xmath276 at one point and @xmath539 limits to @xmath540 , where @xmath246 is an ordinary ray and @xmath541 is a weierstra ray . the construction of the previous section now produces a family @xmath467 for which @xmath542 is a nodal curve of genus @xmath127 , whose closed fiber @xmath420 has three components : @xmath543 and @xmath319 . the exceptional curves meeting @xmath420 at the singular point @xmath334 are @xmath544 , @xmath393 . the roots that are differences of two disjoint members taken from this collection make up a root subsystem @xmath516 of type @xmath545 having @xmath546 as a root basis . moreover , the analogous of lemma [ lemma : specialize ] holds , namely : if @xmath547 , then @xmath548 specializes to an element of @xmath549 if and only if @xmath550 . this suggests the following construction ( taken from @xcite ) . consider the torus @xmath551 . its lattice of one parameter subgroups can be identified with the weight lattice @xmath552 and hence its tensor product with @xmath553 with @xmath554 . the indivisible elements in @xmath552 whose kernel is root lattice of a subsystem of type @xmath545 make up a @xmath179-orbit @xmath555 of a fundamental weight . each of these elements spans an oriented ray in @xmath554 and the collection of such rays defines a toric extension @xmath556 to every subsystem @xmath516 of type @xmath545 are associated two @xmath557-rays and hence two copies of @xmath558 . so if @xmath559 spans of one of the rays and if we let @xmath173 act on @xmath192 in the usual manner : @xmath560 = [ \zeta z_0:z_1]$ ] , then we can form @xmath561 ( which is isomorphic to @xmath562 ) and this glues the two copies of @xmath558 on @xmath551 . notice that @xmath179 acts on @xmath563 . the @xmath179-stabilizer of the boundary torus defined by @xmath559 is the weyl group of the @xmath545-subsystem defined by @xmath564 . let @xmath565 be obtained by removing from @xmath563 the fixed point loci of the reflections in @xmath179 and put @xmath566 this contains @xmath567 as an open subset . since the @xmath568 and the @xmath569-stabilizer of a toric stratum in @xmath570 is a weyl group of type @xmath545 , the added locus is isomorphic to @xmath571 . argueing as before ( see also @xcite ) , we find here we need to deal with the case when @xmath539 tangent to @xmath276 in two points and @xmath539 limits to the union @xmath575 of two weierstra rays . then @xmath467 is such that @xmath542 is s bigon curve and the closed fiber @xmath420 has four irreducible components : @xmath576 and @xmath577 . if @xmath372 is given by blowing up 7 numbered points @xmath578 in @xmath379 as before , then the root system @xmath579 is of type @xmath112 and has root basis @xmath580 . via the identification described in section [ sect : bianti ] we find that the exceptional curves through @xmath334 and without common components with @xmath420 are @xmath581 with @xmath582 . the roots that are differences of two disjoint members taken from this collection , and meeting both @xmath338 or both @xmath339 , make up a root subsystem @xmath583 of type @xmath584 having @xmath585 as root basis . if @xmath586 , then @xmath548 specializes to an element of @xmath173 if and only if @xmath587 . the orbifold fundamental groups of an orbifold of the type @xmath591 , where @xmath176 is an irreducible and reduced root system and @xmath516 is a saturated root subsystem of corank one has essentially been determined in @xcite . it is best described in terms of the extended ( affine ) root system , or rather , of the associated affine coxeter system . we briefly recall the construction . although much of what follows holds in greater generality , let us confine ourselves here to the case when @xmath592 is an affine coxeter diagram of type @xmath593 ( resp . @xmath594 ) : this is @xmath478-shaped tree whose arms have edge length @xmath595 ( resp . @xmath596 ) . so the automorphism group @xmath597 of @xmath592 is a permutation group of a set of 2 ( resp . 3 elements ) . denote its vertex set by @xmath598 . then we have defined an associated artin group @xmath599 given in terms of generators and relations : the generators are indexed by @xmath598 : @xmath600 and @xmath601 commutes with @xmath602 unless @xmath384 and @xmath424 span an edge of @xmath592 in which case we have a braid relation @xmath603 in the following manner . the group @xmath597 acts on @xmath599 by permuting its generators . to @xmath592 is associated a coxeter group @xmath604 ( the quotient of @xmath599 by putting @xmath605 for all @xmath606 ) and a ( tits ) representation of the coxeter group on a real affine space @xmath607 on which @xmath604 acts properly as an affine reflection group . the generating set @xmath598 defines a fundamental simplex @xmath608 . the group @xmath597 acts as a symmetry group on @xmath609 and this action extends affine - linearly to @xmath607 . thus @xmath610 ( a quotient of @xmath611 ) acts on @xmath607 . let @xmath612 denote the complexification of @xmath607 with all its ( affine ) reflection hyperplanes removed . then @xmath612 can be identified with a @xmath610-covering of @xmath613 and @xmath611 can be identified with the orbifold fundamental group of @xmath613 in such a manner that the covering projection @xmath614 is given by the natural map @xmath615 ( @xcite , cor . the inclusion @xmath616 induces a surjection on fundamental groups and essentially amounts to introducing one new relation : a loop around the added divisor gets killed in the fundamental group . the question is therefore how to represent that loop in @xmath611 . this was addressed in @xcite ( lemma 3.8 ff . ) . let us describe this in some detail . for every @xmath606 , the subgraph @xmath617 obtained by removing @xmath384 and the edges connected to it is the graph of a finite coxeter group @xmath618 which maps isomorphically onto the @xmath604-stabilizer of a vertex @xmath619 of @xmath609 . the homomorphism @xmath620 is known to be an embedding . we denote by @xmath621 the image of the _ garside element _ ( see _ op . _ ) of @xmath622 . its image in @xmath618 is the longest element @xmath623 of @xmath618 and @xmath623 takes @xmath609 to a simplex opposite @xmath619 . the opposition symmetry @xmath624 with respect to @xmath619 composed with @xmath623 is represented by an automorphism of @xmath625 and @xmath626 preserves @xmath609 if and only if this automorphism is the restriction of some @xmath627 . let us call @xmath606 _ quasi - special _ if that is the case . then for a quasi - special @xmath606 we have @xmath628 in @xmath611 and this element acts on @xmath607 as @xmath629 . if we have two distinct vertices @xmath630 that are quasi - special , then @xmath631 acts in @xmath607 as translation over @xmath632 . now @xmath632 defines a one parameter subgroup @xmath633 and under the identification of @xmath611 with the orbifold fundamental group of @xmath613 , the lift @xmath634 of @xmath631 represents the conjugacy class of a simple loop in @xmath613 . this is the loop can be obtained by taking the @xmath635-image of a circle @xmath636 of small radius in @xmath637 , applying a translate under the torus @xmath637 so that the circle lies in @xmath638 and then mapping that circle to @xmath613 . we have @xmath639 and so , if we have a toric extension in which such loops become contractible , then in this extension we have the relation @xmath640 . let us now treat the two cases separately . + assume @xmath592 of type @xmath593 . we take as quasi - special vertices one for which @xmath625 is of type @xmath111 ( then the associated element of @xmath597 is the identity ) and the unique one for which @xmath641 is of type @xmath396 ( then the associated @xmath642 is not the identity ) . the loop in question is associated to the translation @xmath643 and so we are imposing the identity @xmath644 . hence we can eliminate @xmath79 and we find : [ thm : fund - group-2,1,1 ] the orbifold fundamental group of @xmath645 is the largest quotient of the affine artin group @xmath646 for which @xmath647 is of order @xmath122 and conjugation by @xmath647 permutes the generators ( indexed by @xmath598 ) according to the nontrivial involution . assume now @xmath592 of type @xmath594 . we let @xmath606 be a terminal vertex ( so that @xmath625 is of type @xmath112 ) and let @xmath648 be the unique vertex @xmath649 connected with @xmath384 ( so that @xmath641 is of type @xmath650 ) . both are quasi - special , define subgraphs @xmath651 and @xmath652 ( here the notation indicates the type ) and define the same element of @xmath597 ( namely the unique involution which fixes @xmath384 ) . then the loop in question is represented by @xmath653 and hence : [ thm : fund - group-2,2 ] the orbifold fundamental group of @xmath654 is the quotient of the semidirect product of the affine artin group @xmath655 with the symmetry group @xmath656 of the @xmath594-graph defined by the relation @xmath657 . we may also write this as a semidirect product of @xmath656 and a quotient of @xmath655 . the quotient is then obtained by imposing three such relations : one for every terminal vertex , so that @xmath656 still acts on it .
we give a description of the kontsevich - zorich strata for genus 3 in terms of root system data . for each non - open stratum we obtain a presentation of its orbifold fundamental group .
for a large class of problems , the interaction between the electromagnetic field and macroscopic magneto dielectrics is modelled by the use of a permittivity @xmath0 and permeability @xmath1 . in order to consider a broad range of frequencies of radiation , it becomes necessary to account for losses and dissipation in matter . however it has proven difficult to construct a theory that accounts for the effects of dispersion and dissipation in systems where quantum mechanical behaviour is important ; e.g. the casimir effect @xcite , quantum friction @xcite , or even analogues of hawking radiation @xcite . although a great deal of progress can be made through applying the fluctuation dissipation theorem @xcite , the absence of for instance a hamiltonian operator can make it difficult to resolve conflicting predictions ( e.g. @xcite ) . during recent years , much progress has been made towards a rigorous quantisation scheme that accounts for the effects of dispersion and dissipation , see for example @xcite and references therein . in this work we shall apply the theory presented in @xcite , which is a generalization of the huttner barnett theory @xcite and uses a bath of simple harmonic oscillators to account for the energy lost from the electromagnetic field . the usual frequency domain constitutive equations @xmath2 and @xmath3 are recovered from the equations of motion , with the relative permittivity @xmath4 and permeability @xmath5 obeying the kramers - kronig relations @xcite . one of the significant consequences of this theory ( which was also pointed out earlier by huttner and barnett @xcite ) , is that the excitations of the electromagnetic field and medium are strongly coupled so that one must work in terms of _ polaritons _ instead of photons : unlike photons these quanta have no set relationship between their frequency @xmath6 and wave vector @xmath7 . we note that the theory was initially developed for isotropic stationary media , but can be generalised to bianisotropic and moving media @xcite . here we shall explore the effects of the motion of a material and the time dependence of its properties on the excitation of the system when it is initially prepared in the ground state . although such dynamic casimir type effects have been studied before @xcite , one typically does not include the effects of dispersion and dissipation , which we include here within the full generality of the formalism of macroscopic qed . our analysis predicts the excitation rate of polaritons within the material as a function of @xmath6 and @xmath7 , and can be applied to any material so long as the permittivity and permeability satisfy the kramers kronig relations . the excitations we find do not obey a dispersion relation , but they each possess a time dependent electric field able to excite a detector embedded within the material . they also produce radiation that could be measured by a photon detector placed outside of the material , although we do not calculate this process here . in the first section of this paper we explore the classical lagrangian and hamiltonian necessary to describe a dispersive , lossy dielectric that has time dependent properties , or is in motion . we briefly show that in both cases ( see figure [ fig : system ] ) the effects of motion or time dependence can be subsumed within new effective material susceptibilities . using time dependent perturbation theory , we then calculate the excitation rate of pairs of polaritons due to the time dependence or motion of the medium . we find that from the perspective of macroscopic qed time dependent material properties and material motion contribute separately to the hamiltonian , even though one would expect a moving spatial distribution of permittivity to be indistinguishable from a moving medium . after developing the general theory we treat three illustrative cases ( see figure [ fig : system ] ) : ( a ) an infinite homogeneous medium performing a linear oscillatory motion ; ( b ) an infinite homogeneous medium where the permittivity oscillates in time ; and ( c ) a ` bump ' in the permittivity moving uniformly through an otherwise homogeneous dielectric . the final example is inspired by the recent optical experiments investigating laboratory analogues of hawking radiation @xcite . around a fixed position ; b ) the permittivity of a uniform medium oscillates around a fixed value , @xmath8 ; c ) a spatially dependent change to the permittivity @xmath9 , moves at a constant velocity @xmath10 through an otherwise uniform medium of permittivity @xmath11 , emitting radiation as it moves . to calculate the emission rates we apply time dependent perturbation theory to macroscopic qed @xcite.[fig : system],height=151 ] in this section we construct the classical theory of the electromagnetic field interacting with a moving or time dependent material that exhibits dispersion and dissipation . the lagrangian of @xcite is extended in a similar fashion to @xcite , in this case accounting for non - relativistic motion and an arbitrary time dependence of the permittivity profile . the dynamical variables of the electromagnetic field are the vector potential @xmath12 and the scalar potential @xmath13 , which are related to the electric and magnetic field strengths by @xmath14 and @xmath15 respectively . the dissipation of electromagnetic energy is governed by the coupling of the electromagnetic field to a field of simple harmonic oscillators @xmath16 present throughout space , with every possible natural frequency @xmath6 . the lagrangian density for our system is given by @xmath17 \end{split}\ ] ] and is valid to first order in the velocity @xmath18 of the material , which at this point we allow to be spatially dependent . for simplicity we have set @xmath19 throughout , which amounts to ignoring the second oscillator bath that appears in @xcite , although this can be re introduced with no fundamental modifications to our results . the coupling between the field of oscillators and the electromagnetic field is mediated via a term that is proportional to a quantity @xmath20 which in this case is a scalar quantity that depends on space , time and frequency . the second coupling term @xmath21 is given in terms of @xmath20 by @xmath22 , and is due to the lorentz transformation of the field strengths between reference frames ( a phenomenon we shall often refer to as polarization mixing ) . here we treat the time dependence of the medium as a perturbation to an otherwise isotropic , time independent background : @xmath23 . the background permittivity of the medium @xmath24 is related to this time independent coupling term by the expression given in @xcite : @xmath25/\pi}$ ] . the hamiltonian of the system is found in terms of the canonical momenta and the lagrangian ( see for example @xcite ) and is given by @xmath26.\ ] ] where the canonical momenta of the electromagnetic field @xmath27 and of the oscillator field @xmath28 are given by @xmath29 @xmath30 the scalar potential @xmath13 is not a dynamical variable , and can be removed from the hamiltonian as is done in e.g. @xcite . because we treat the time dependence of the dielectric as having a small effect on the total field , we divide this hamiltonian up into two parts , @xmath31 where @xmath32 is the hamiltonian of a time - independent dielectric , similar to that of @xcite but with @xmath19 , given by @xmath33\ ] ] and @xmath34 is the interaction hamiltonian due to the motion and time dependence of the dielectric , given by , @xmath35.\ ] ] the interaction hamiltonian @xmath34 contains three terms : the first accounts for the fact that the bath of oscillators is in motion ; the second is due to the polarization mixing due to the motion ; and the third term is due to the time dependences of the permittivity , which could for example be due to time dependent boundaries or simply the time - varying permittivity of a stationary object . before embarking on the quantum mechanical calculation , we derive the classical equations of motion and show how the time dependence of the system can be seen as a modification of the relative permittivity . as an example , consider the case of a spatially homogeneous medium moving with an arbitrary time dependent velocity , where @xmath36 . through the use of the euler - lagrange equations ( see e.g. @xcite ) , we obtain the equations of motion for the oscillator bath @xmath37\mathbf{x}_{\omega}\left(\mathbf{x},t\right)=\alpha_{b}\left(\omega\right)\mathbf{e}\left(\mathbf{x},t\right)\ ] ] and for the field @xmath38 with the polarisation @xmath39 given by @xmath40 for simplicity we have ignored the polarisation mixing term @xmath41 , concentrating on only the electric response of the material . in order to see how the time dependence of the medium affects the material parameters , we solve equations ( [ eq : oscillatorequationsofmotion ] ) and ( [ eq : ewaveeq ] ) . the solutions to ( [ eq : oscillatorequationsofmotion ] ) are given by @xmath42 where the @xmath43 are the homogeneous solutions to ( [ eq : oscillatorequationsofmotion ] ) and are of the general form @xmath44 where @xmath45 are arbitrary functions of position and the lower limit in the integral , @xmath46 is the initial time of the evolution of the system where the amplitudes are simply @xmath47 . in the quantum theory , these amplitudes will become the creation and annihilation operators of the quantum fields in the same way as the theory developed in @xcite . the oscillator green s function @xmath48 in ( [ eq : oscillatorsolutions ] ) satisfies @xmath49g_{x_{\omega}}\left(\mathbf{x},\mathbf{x'},t , t'\right)=\delta^{(3)}\left(\mathbf{x}-\mathbf{x'}\right)\delta\left(t - t'\right)\ ] ] the retarded solution ( zero for @xmath50 ) to which is given by @xmath51\delta^{(3)}\left(\mathbf{x}+\intop_{t'}^{t}\mathbf{v}\left(t_{1}\right)dt_{1}\right).\ ] ] substituting ( [ eq : oscillatorgreen ] ) into ( [ eq : oscillatorsolutions ] ) gives an expression for the amplitudes of the oscillator field in terms of the field @xmath52 and the arbitrary amplitudes @xmath45 , @xmath53\mathbf{e}\left(\mathbf{x}+\intop_{t'}^{t}\mathbf{v}\left(t_{1}\right)dt_{1},t'\right)+\mathbf{x}^{h}_{\omega}\left(\mathbf{x},t\right).\ ] ] the meaning of this integral expression is simply that the oscillator amplitudes at @xmath54 no longer depend solely on the strength of the field at @xmath54 ( as it does in @xcite ) but also on the previous positions of the moving oscillator @xmath55 for times @xmath56 _ before _ @xmath57 . the motion of the material thus leads to a non local response , due to the fact that energy dissipated from the electromagnetic field is carried away from the point where it was absorbed . the wave equation for the electric field is found through substituting expression ( [ oscill2 ] ) into ( [ polarisation ] ) , and combining the resultant expression with ( [ eq : ewaveeq ] ) @xmath58 where the non - local effective susceptibility of the system @xmath59 is given by @xmath60.\label{movsuc}\ ] ] the theta function above ensures that the effective susceptibility is non - zero only for times past , enforcing causality and consequently also the kramers kronig relations . in the limit @xmath61 , the wave equation ( [ eq : waveequation ] ) reduces to the usual stationary wave equation in dispersive media ( see e.g. @xcite ) , and ( [ movsuc ] ) reduces to the local expression @xmath62 , where @xmath63 is the fourier transform of @xmath64 . the source of the electromagnetic field @xmath65 that appears in the wave equation ( [ eq : ewaveeq ] ) depends on the arbitrary functions @xmath45 and is given by the non - local expression does not have units of electric current . ] @xmath66.\ ] ] this current has the same interpretation as in @xcite : the un - driven part of the motion of the bath of oscillators is the source of the electromagnetic field in an absorbing medium . in @xcite , the @xmath45 are related to the amplitude of the current @xmath67 in a local manner . here , the relative motion of the medium @xmath68 means that the current at @xmath54 now depends on the @xmath45 at @xmath69 . the nature of the non - locality in both the susceptibility ( [ movsuc ] ) and the current ( [ current ] ) depends upon the motion . in analogy to @xcite , the solution to ( [ eq : waveequation ] ) written in terms of the electromagnetic green s function @xmath70 where @xmath71 is a bi - tensor satisfying @xmath72 where @xmath73 is equal to ( [ movsuc ] ) without the spatial delta function . finding the solution of ( [ eq : greensfunctionwaveequation ] ) would be essential in any calculation involving the electric field . in the cases treated in @xcite , the difficulty of finding solutions resides in the complexity of the geometry . in this case though , even in homogeneous media , the integro - differential equation above presents further difficulties due to its non - locality . yet in a few simple cases , some progress can be made . given the homogeneity of the medium in this case , ( [ eq : greensfunctionwaveequation ] ) can by fourier transformed so that it reduces to the integral equation @xmath74 where the kernel of the integral represents the fourier transformed susceptibility of the system and is given by @xmath75 for the case of constant velocity @xmath76 , the wave equation ( [ eq : greensfunctionwaveequation ] ) simplifies to that given in @xcite ( again , ignoring polarisation mixing ) where the doppler shifted frequency @xmath77 appears in the argument of the susceptibility , @xmath78\mathbb{1}_{3}\right\}\cdot\mathbf{g}\left(\mathbf{k},\omega,\omega_{2}\right)=-2\pi\delta(\omega-\omega_{2})\mathbb{1}_{3}.\ ] ] the green function is then equal to the inverse of the square bracketed matrix on the left times @xmath79 . in other words , the constant motion of the dielectric , gives rise to a new effective permittivity in which the frequency response is shifted by @xmath80 . now consider a slightly more complicated case , that of a time dependent oscillatory motion in the @xmath81-direction , with frequency @xmath82 , @xmath83 , where @xmath84 is the maximum displacement . in this case the integral over the velocity in the susceptibility ( [ eq : fouriersusc ] ) becomes @xmath85 the susceptibility ( [ eq : fouriersusc ] ) can then be written as @xmath86 where we applied the generating function for bessel functions @xcite @xmath87 where @xmath88 are the bessel functions of the first kind . expression ( [ oscsuc ] ) demonstrates a coupling between the frequencies of the field arising from the oscillation , occurring in discrete multiples of the oscillation frequency @xmath82 . it is interesting to note that the susceptibility vanishes when @xmath89 equals a zero of a bessel function , which for a fixed @xmath90 and @xmath91 excludes the coupling to those frequencies @xmath92 where @xmath93 . in the limiting case when the argument of the bessel functions , @xmath89 , becomes very large , the material behaves like the vacuum since the bessel functions all tend to zero . for very small @xmath94 , only the @xmath95 survives and the material behaves as if it were stationary . this occurs for very large wavelengths or in the limit of a vanishing displacement amplitude . it is still difficult to exactly solve ( [ eq : fouierwaveeq ] ) for the green function @xmath96 . however , if we make for example the simplifying approximation that @xmath97 and @xmath98 or smaller then the delta function and the susceptibility can be removed from under the summation sign in ( [ oscsuc ] ) and the system behaves as if it had the effective permittivity given by the sum over the product of the bessel functions . the above brief examination of the classical physics of electromagnetism interacting with a moving dielectrc demonstrates that for most cases of interest it is difficult to find exact solutions to the equations of motion . in order to establish quantitative results in general , proceeding via perturbation theory seems the best approach and is the one we adopt from this point on we now quantize the classical theory outlined in the previous section , applying it to the situations illustrated in figure [ fig : system ] . most of the formula remain formally quite similar , but we must replace the classical fields with field operators that obey the canonical commutation relations @xcite , @xmath99=i\hbar\mathbb{1}_{3}\delta\left(\mathbf{x}-\mathbf{x'}\right ) \\&\left[\mathbf{\hat{x}}_{\omega}\left(\mathbf{x},t\right),\mathbf{\hat{\pi}}_{\mathbf{x}_{\omega'}}\left(\mathbf{x'},t\right)\right]=i\hbar\mathbb{1}_{3}\delta\left(\mathbf{x}-\mathbf{x'}\right)\delta\left(\omega-\omega'\right ) . \end{split}\ ] ] we work in the interaction picture @xcite , where the time dependence of the operators is generated by the bare hamiltonian @xmath100 , given by the operator equivalent of ( [ eq : h0 ] ) and that of the quantum state by the interaction hamiltonian @xmath101 given by the operator equivalent of ( [ eq : pert ] ) where the full hamiltonian is given by @xmath102 . with the time dependence of the operators being generated by @xmath100 , the canonical operators are expanded in terms of a set of creation and annihilation operators @xmath103 , @xmath104 as @xmath105\\ \hat{\pi}_{\mathbf{a}}\left(\mathbf{x},t\right)&=\int d^{3}\mathbf{x}'\intop_{0}^{\infty}d\omega'\left [ \mathbf{f}_{\mathbf{\pi_{a}}}\left(\mathbf{x},\mathbf{x'},\omega'\right)\cdot\mathbf{\hat{c}}\left(\mathbf{x'},\omega'\right)e^{-i\omega't}+h.c\right]\\ \mathbf{\hat{x}}_{\omega}\left(\mathbf{x},t\right)&=\int d^{3}\mathbf{x}'\intop_{0}^{\infty}d\omega'\left [ \mathbf{f}_{\mathbf{x}}\left(\mathbf{x},\mathbf{x'},\omega,\omega'\right)\cdot\mathbf{\hat{c}}\left(\mathbf{x'},\omega'\right)e^{-i\omega't}+h.c\right]\\ \hat{\pi}_{\mathbf{x_{\omega}}}\left(\mathbf{x},t\right)&=\int d^{3}\mathbf{x}'\intop_{0}^{\infty}d\omega'\left [ \mathbf{f}_{\mathbf{\pi_{x}}}\left(\mathbf{x},\mathbf{x'},\omega,\omega'\right)\cdot\mathbf{\hat{c}}\left(\mathbf{x'},\omega'\right)e^{-i\omega't}+h.c\right]\end{aligned}\ ] ] where the expansion coefficients are identical to those given in @xcite , and are given for reference here in appendix [ apa ] . there are also similar expansions for the @xmath106 and @xmath107 operators . the operators @xmath108 and @xmath109 represent the creation and annihilation of quanta of the coupled field matter system ( polaritons ) and obey bosonic commutation relations , @xmath110=\mathbb{1}_{3}\delta\left(\mathbf{x}-\mathbf{x'}\right)\delta\left(\omega-\omega'\right ) \\&\left[\mathbf{\hat{c}}\left(\mathbf{x},\omega\right),\mathbf{\hat{c}}\left(\mathbf{x'},\omega'\right)\right]=0 \end{split}\ ] ] the expansion given in ( [ expansion ] ) is chosen such that it diagonalises the bare hamiltonian , @xmath111 for more details about this diagonalization see @xcite . we now apply the usual methods of time dependent perturbation theory to find the effect of the motion or time dependence of the medium on the excitation of polaritons . in the absence of any perturbation , we take the system to be prepared in its ground state @xmath112 ( defined as the state where @xmath113 ) . given that , to leading order , the introduction of the interaction hamiltonian @xmath114 will lead to the creation of pairs of polaritons we represent the wave function of the system as @xmath115 where the expansion coefficient obeys @xmath116 , in accordance with bosonic exchange symmetry . the physical meaning of @xmath117 is as the probability amplitude for the creation of a pair of current excitations in the material , located at positions @xmath118 and @xmath119 , oscillating at frequencies @xmath120 and @xmath121 , and pointing in the @xmath122 and @xmath123 directions . inserting ( [ psi ] ) into the schdinger equation @xmath124 , we find the rate of change of the expansion coefficient is given by @xmath125 due to the form of the interaction hamiltonian ( [ eq : pert ] ) , the rate of change of the rank-2 tensor @xmath126 separates into the sum of two parts , @xmath127 the first term @xmath128 arises from the first two terms in the interaction hamiltonian ( [ eq : pert ] ) and represents the effect of the motion of the medium , both through the movement of energy within the bath of oscillators , and the mixing of the electromagnetic field polarization between reference frames . the second term , @xmath129 comes from the final term in ( [ eq : pert ] ) , and represents the effect of any time dependence in the permittivity . evaluating ( [ asymzeta ] ) by substituting the expansion of the operators ( [ expansion ] ) into the interaction hamiltonian and using the commutation relations ( [ commutation ] ) , the dyadic form the rate of change of the two parts to the expansion coefficient ( [ rate ] ) is found to be @xmath130 + 1\leftrightarrow2 \end{split}\ ] ] and @xmath131 where the notation ` @xmath132 ' indicates the repetition of the preceding expression but with the two particles interchanged ( which in the above expressions involves both taking the transpose and swapping subscripts @xmath133 and @xmath134 ) . it is evident from expressions ( [ zeta_v ] ) and ( [ secondterm ] ) that the rate of polariton excitation is in general quite different for time dependent and moving media . for instance , a time dependent permittivity profile constructed to appear as a moving material would have @xmath135 , whereas true motion has in general both non zero @xmath136 and @xmath137 . in the remainder of the paper we shall evaluate polariton excitation rates implied by ( [ zeta_v ] ) and ( [ secondterm ] ) for the three cases shown in figure [ fig : system ] . to be specific we assume the simplest case of a lossy dispersive medium , where the background dielectric function @xmath138 is lorentzian , with a resonant frequency @xmath139 @xmath140 where we assume the arbitrary values @xmath141 , and damping constant @xmath142 . the first calculation we perform is the polariton emission rate within an infinite homogeneous medium performing an oscillatory motion . due to the lack of boundaries and the translational invariance , the second term in ( [ rate ] ) , @xmath143 is equal to zero , and the probability amplitude for emitting a pair of polaritons is then equal to the integral of @xmath144 over the time interval @xmath145 $ ] ( as is typical in such calculations , it is assumed that the interaction hamiltonian is ` turned on ' at the initial time @xmath146 ) . the absolute value squared of the result divided by @xmath147 gives us the average net excitation rate of polariton pairs over the time interval @xmath147 . over a very long time interval @xmath148 this is given by @xmath149 the emission rate given by ( [ eq : fermi ] ) is valid even for spatially dependant velocities @xmath68 , as occurs e.g. for rotating bodies . however here we make the simplification that the velocity does not depend on position , in which case as is evident from ( [ zeta_v])the time dependence of @xmath150 can be factored out from the spatial dependence . for example , in the case of constant velocity the time dependence of ( [ zeta_v ] ) is given by the factor @xmath151 so that @xmath152 the emission rate ( [ eq : fermi ] ) is then reduced to @xmath153 where @xmath154 . the argument of the delta function is only zero at the one point @xmath155 , where the integrand is zero . this leaves , @xmath156 as expected . when the velocity exhibits a time dependence then in general the emission rate @xmath157 will be non zero . consider some time dependent velocity @xmath158 . in order to analyse the emission rate as a function of frequency and wave vector , we work in terms of the fourier transform of @xmath136 , @xmath159 where the quantity @xmath160 is given in appendix [ apb ] and is a sum of terms depending of products of green s functions and combinations of the permittivity at frequencies @xmath120 and @xmath121 . the amplitude @xmath161 is proportional to the probability amplitude for exciting a pair of polaritons with wave - vectors @xmath90 and @xmath162 and frequencies @xmath120 and @xmath121 from the ground state , due to the motion of the medium . consider the specific case of an oscillatory motion with frequency @xmath82 : @xmath163 , where @xmath84 is the maximum displacement from the mean position . taking the absolute value squared of ( [ defa ] ) and integrating with respect to time , the equivalent of ( [ eq : timedep ] ) now equals @xmath164\ ] ] the proof of which is given in appendix . while the second term on the right of ( [ eq : delta ] ) fails to contribute to the emission rate ( owing to @xmath120 , @xmath121 and @xmath82 all being positive ) , the first term does . combining ( [ defa ] ) and ( [ eq : delta ] ) with the expression for the net rate of excitation ( [ emissionexp ] ) gives the emission rate per unit volume @xmath165 @xmath166 where the ` spectral density ' for the emission of polariton pairs @xmath167 is equal to @xmath168 with @xmath169 the heaviside step function . this dimensionless spectral density depends only on the wave vector and frequency since the translational symmetry of this system guarantees momentum conservation for the two polaritons , @xmath170 , and energy conservation implies that the total energy of the pair of particles must equal that due to the motion : @xmath171 . note that the time dependence of the velocity sets this relationship between @xmath120 and @xmath121 , and that for a general motion this may be more complicated . the excitation rate ( [ eq : excitation ] ) evidently scales quadratically with the maximum displacement @xmath84 . however , the dependence on the oscillation frequency @xmath82 is somewhat more intricate . as can be seen from the expression for @xmath172 given in appendix [ apb ] , as well as figure [ fig : emissionamplitude_full]a , the largest contribution to the spectral density @xmath167 comes from regions where the frequency and wave vector are close to satisfying the dispersion relations for electromagnetic waves @xmath173 and @xmath174 and where the frequency matches the resonant frequency of the dielectric @xmath139 , and the shifted resonance at @xmath175 . the largest emission occurs in the region close to where the dispersion curves for radiation intersect with the material resonances . we note that there is a term that contributes to ( [ eq : excitation])given as @xmath176 in appendix [ apb]which diverges when @xmath177 but is zero for all other frequencies . this has been omitted from figure [ fig : emissionamplitude_full]a . physically , this problematic term represents the emission rate for two polaritons at the same frequency from the same position . this is specific to moving media and does not recur in the remainder of the paper . it nevertheless deserves further attention and will be treated in future work . $ ] , due to the oscillatory motion of a homogeneous dielectric . the dielectric function of the material @xmath138 is given by the lorentzian response ( [ lorentzian ] ) with a resonance at @xmath139 , while the oscillation frequency of the motion is arbitrarily chosen as @xmath178 to clearly separate the curves . the spectral density is mostly concentrated around frequencies in the vicinity of the resonant frequency of the material @xmath139 , the shifted resonant frequency @xmath175 as well as along the two dispersion curves satisfying @xmath179 , and the shifted dispersion curve @xmath180 . the vertical line at @xmath181 represents the upper boundary of the area contributing to the emission rate ( [ eq : excitation ] ) ; the shaded area to right of this does not contribute to the total emission rate . the black circle points to an example of a region where the shifted dispersion curve intersects with the resonance at @xmath139 ; the emission rate density is much more intense and somewhat spread out around these areas . b ) : angular dependence of spectral density @xmath182 where the frequency and wave vector magnitude are arbitrarily chosen to be @xmath183 and @xmath184 respectively corresponding to the centre of the black circle in ( a ) . the distance of the surface from the centre of the graph shows the amplitude of the emission rate for varying directions of @xmath90 . the strongest excitation of polaritons occurs in the direction of motion.,height=264 ] the second contribution to the emission rate ( [ secondterm ] ) @xmath143 comes from the time dependence of the material response @xmath185 . for moving media , this term can be non zero either due to moving inhomogeneities or changing boundaries . this term can also be used to model changes in the permittivity due to external forces , such as those in dynamical casimir experiments @xcite or optical analogues of hawking radiation @xcite , examples of both of which we now consider . inserting the expansion coefficients listed in appendix [ apa ] into ( [ secondterm ] ) , we find the rate of change of the probability amplitude for exciting a pair of polaritons is given by @xmath186 + 1\leftrightarrow2 \end{split}\ ] ] we now consider two particular applications of ( [ zetadyn ] ) , firstly where the permittivity of the medium uniformly oscillates as a function of time , and secondly where a travelling pulse - like perturbation @xmath187 to the permittivity moves through the medium at a uniform velocity . consider a time dependent change to the permittivity of the form @xmath188 corresponding to a periodic change in the medium over all space with frequency @xmath82 . in this case , the time dependence can be factored out as in the previous section , and the identity ( [ eq : delta ] ) can be applied . the spectral density appearing in the polariton emission rate per unit volume ( the analogue of ( [ eq : excitation ] ) ) is again dimensionless and found to be @xmath189 where @xmath190\\&+1\leftrightarrow2 . \end{split}\ ] ] with ` @xmath132 ' again indicating an interchange of the two particles ( which now involves swapping the subscripts @xmath133 and @xmath134 , interchanging @xmath90 for @xmath191 and taking the transpose ) . as in the case of the moving dielectric that we just discussed , the emission conserves momentum @xmath170 and the energy of the pair of polaritons is taken from the oscillation : @xmath171 . equation ( [ eq : dyncascoeffgen ] ) can be further simplified in the particular case where @xmath192 ( i.e. the change in the permittivity has the same frequency dependent response as the background ) , @xmath193{\rm im}[\chi_{b}\left(\omega_{2}\right)]}\frac{\omega^{2}_{1}}{c^{2}}\mathbf{g}^{\dagger}\left(\mathbf{k},\omega_{1}\right)\cdot\left [ \chi_{b}^{\star}\left(\omega_{2}\right)\frac{\omega^{2}_{2}}{c^{2}}\mathbf{g}^{*}\left(-\mathbf{k},\omega_{2}\right)+\mathbb{1}_{3}\right]+1\leftrightarrow2.\ ] ] as is evident from ( [ eq : emissdensperm])and in similarity to the time dependent material velocity investigated in the previous section the time dependence of @xmath194 gives rise to emission only for frequencies in the range @xmath195 . the emission rate per unit volume is then given by integrating ( [ eq : emissdensperm ] ) over wave vector and frequency . the frequency and wave vector dependence of the spectral density of polariton emission are plotted in figure [ fig : dynamicamplitude ] . due to the lack of any preferred direction in the changing permittivity @xmath194 the emission is isotropic , but otherwise it is in many respects similar to that of a dielectric in oscillatory motion . however , note that the emission rate is not proportional @xmath196 in this case . $ ] as a function of @xmath6 and @xmath197 , for a dielectric function oscillating as a function of time with frequency @xmath82 . the background dielectric function of the material @xmath138 is given by the lorentzian response ( [ lorentzian ] ) with a resonance at @xmath139 , while the oscillation frequency of the material properties is chosen as @xmath178 to clearly separate the curves . the regions of high emission occur at the same points as shown for the moving dielectric in figure [ fig : emissionamplitude_full ] . b ) : angular dependence of spectral density @xmath198 where the frequency and wave vector magnitude are arbitrarily chosen to be @xmath183 and @xmath184 respectively corresponding to the centre of the black circle in ( a ) . the colour in this subfigure only serves to illustrate that the shape is a sphere , indicating isotropic emission.,height=264 ] as a final , more involved example of macroscopic qed applied to time dependent media , we address the case of a medium through which a perturbation of the refractive index travels at a constant velocity @xmath10 , producing pairs of polaritons . recent work @xcite has established a connection between such a process and an analogue of hawking radiation @xcite . here we do not emphasize the connection to general relativity , but rather look for a description of such an emission process that fully accounts for the effects of dispersion and dissipation . to the authors knowledge , previous treatments have not fully accounted for such effects . we assume that the travelling perturbation to the permittivity can be represented in terms of the function @xmath199 taking the form @xmath200 unlike the case of a truly moving medium , @xmath201 is not restricted to non - relativistic velocities . in this case we find the following expression for the rate of change of the polariton amplitude , @xmath202 where the dyadic @xmath172 is given by @xmath203\\ % \frac{1}{2\pi}\sqrt{\epsilon_{i}\left(\omega_{1}\right)\epsilon_{i}\left(\omega_{2}\right)}\frac{\omega^{2}_{1}}{c^{2}}\mathbf{g}^{\dagger}\left(\mathbf{k}_{1},\omega_{1}\right)\cdot\left[\mu_{0}c^{2}\sqrt{\frac{2\epsilon_{0}}{\pi}}\intop_{0}^{\infty}d\omega\frac{\sqrt{\omega\epsilon_{i}\left(\omega\right)}\beta\left(\omega\right)}{\omega{}^{2}-\left(\omega_{2}-i\omega0^{+}\right)^{2}}\frac{\omega^{2}_{2}}{c^{2}}\mathbf{g}^{*}\left(\mathbf{k}_{2},\omega_{2}\right)+\mathbb{1}_{3}\right]\\ + 1\leftrightarrow2\label{ahawking}\end{gathered}\ ] ] for simplicity , we choose the change in permittivity to have the same dispersion as the background material @xmath204 , although presumably physically this need not be the case . equation ( [ ahawking ] ) then reduces to @xmath205{\rm im}[\chi\left(\omega_{2}\right)]}\frac{\omega^{2}_{1}}{c^{2}}\mathbf{g}^{\dagger}\left(\mathbf{k}_{1},\omega_{1}\right)\cdot\left[\chi_{b}^{\star}\left(\omega_{2}\right)\frac{\omega^{2}_{2}}{c^{2}}\mathbf{g}^{*}\left(\mathbf{k}_{2},\omega_{2}\right)+\mathbb{1}_{3}\right]+1\leftrightarrow2.\label{eq : ahawking}\ ] ] defining the net emission rate in terms of a spectral density that is now a function of two wave vectors and frequency @xmath206 we find @xmath167 to be @xmath207 where we applied @xmath208.\ ] ] the expression for the spectral density has a similar form to that given in the previous sections , except that it now depends on two wave vectors @xmath209 and @xmath210 , due to the momentum exchanged between the polaritons and the moving perturbation ; it also now has dimensions of @xmath211 . in fact , the form of ( [ eq : hawkingspectraldensity ] ) can be motivated from fairly simple physical considerations : the spatial distribution of the moving perturbation @xmath194 is determined by the function @xmath212 , which has a corresponding fourier spectrum @xmath213 . the two polaritons can exchange momentum with the moving perturbation so long as the conservation law @xmath214 is satisfied . energy conservation must also be obeyed , with the pulse containing frequencies @xmath215 so that @xmath216 . combining these two conservation laws leads to @xmath217 , with the rate of pair production being proportional to the amplitude of the relevant fourier amplitude of the perturbation , @xmath218 . the @xmath169 function in ( [ eq : hawkingspectraldensity ] ) ensures that the energy of both of the polaritons is positive , while @xmath219 scales the emission rate depending on how close the frequencies @xmath120 and @xmath121 are to the resonances of the material ( where @xmath220 is large ) , and how close the dispersion relations @xmath221 are to being fulfilled ( where the green function @xmath71 is large ) . from ( [ eq : ahawking ] ) it is evident that the peak pair production will occur when the dispersion relation is fulfilled while the frequency of one member of the pair is at a resonance of the material . in figure [ fig : dynamicamplitude_full ] we plot the dependence of @xmath222 as a function of both the relative angle between @xmath209 and @xmath210 , and the magnitude of the modulus of both wave vectors for a fixed angle between them . we take the particular case where the moving perturbation to the permittivity takes the form of a gaussian , @xmath223 with the area under the function @xmath212 equal to @xmath224 . the spectral density for the excitation of polariton pairs ( [ eq : hawkingspectraldensity ] ) then becomes @xmath225^{2}\right ) \theta(\mathbf{v}\cdot(\mathbf{k}_{1}+\mathbf{k}_{2})-\omega)\ ] ] it is evident from ( [ dens ] ) that there is a trade off in the spectral density between the requirement of energy conservation , and the fourier spectrum of the moving perturbation . the maximum in the fourier spectrum @xmath226 in this case occurs when @xmath227 , which is where the energy of one of the polaritons @xmath228 is negative , and thus the spectral density is zero . meanwhile when @xmath229 , both polaritons can have positive energy , but the exponential factor @xmath230^{2}/2)$ ] reduces the spectral density exponentially with the magnitude of @xmath231 . spatially sharp , quickly moving perturbations thus have relatively large emission rates for pairs of polaritons , and these pairs tend to be emitted away from the axis of propagation . this is in broad agreement with e.g. @xcite but here derived without the analogy to general relativity . spatially broad perturbations correspond to large values of @xmath232 , and thus small values of @xmath231 . as the velocity of the perturbation drops to @xmath233 , the @xmath169 function in ( [ dens ] ) picks out ever larger magnitudes of @xmath231 , which are ever further from fulfilling the dispersion relation ( i.e. where the green function @xmath234 in ( [ eq : ahawking ] ) becomes ever smaller ) . in this zero velocity limit the spectral density thus reduces to zero , as expected . $ ] for an arbitrary inclination angle @xmath235 . the background dielectric function of the material @xmath138 is given by the lorentzian response ( [ lorentzian ] ) with a resonance at @xmath139 . the velocity is taken to be @xmath236 and the gaussian pulse width as @xmath237 . the spectral density is significant at frequencies in the vicinity of the resonant frequency of the material ( vertical line at @xmath183 ) , the shifted resonant frequencies @xmath238 ( a and b ) and along the dispersion curve satisfying @xmath239 ( see for example line d ) and the shifted dispersion curve @xmath240 ( see for example line c ) . the shaded area to the right of the line @xmath241 does not contribute to the total emission rate due to the theta function in the spectral density ( [ dens ] ) . the spectral density is greatest around intersections between dispersion curves and/or resonances of the material . the black circle points to an example of a region where two resonance curves intersect but similar intersections occur between resonances and dispersion curves or pairs of dispersion curves . b ) angular dependence of the spectral density @xmath242 for a fixed frequency @xmath243 where the frequency and wave vector magnitude are arbitrarily chosen to be @xmath183 and @xmath244 respectively corresponding to the centre of the black circle in ( a ) , for varying angle between @xmath245 and @xmath90 . the rate is seen to be negligible for all directions except along the surface of a number of cones traced out along rings of constant inclination angle @xmath169.,height=264 ] figure [ fig : dynamicamplitude_full]a confirms that the emission rate spectral density contains terms that contribute significantly for frequencies and wave - vectors where one of the pairs is close to fulfilling the dispersion relation and/or close to the resonant frequency of the material response . this subfigure is plotted for an arbitrarily chosen angle between @xmath209 and @xmath210 , with both wave vectors having equal magnitude . figure [ fig : dynamicamplitude_full]b represents the angular dependence of the spectral density of the emission , varying the angle between @xmath209 and @xmath210 for a fixed frequency and equal magnitude of the two wave vectors . the emission is concentrated in several cone - like regions . these cones correspond to either the shifted dispersion curves or the shifted resonances in figure [ fig : dynamicamplitude_full]a . increasing the absorption within the dielectric response has the effect of blurring the lines of [ fig : dynamicamplitude_full]a and of thickening the shells of the cone - like shapes of [ fig : dynamicamplitude_full]b . this effectively means that it becomes possible to excite polaritons that lie further from the resonance of the material or the dispersion curve for electromagnetic waves . the choices of plot in figure [ fig : dynamicamplitude_full ] do not encode the complete radiation pattern from the moving moving perturbation but serve to show under what conditions the emission of polariton pairs is increased , as well as the directional distribution of the emission . it would be too lengthy to fully explain the different regimes of this effect here , and further results will be given in a future publication . it is interesting to compare this effect with those explored in sections [ homed ] and [ sec : tdp ] ; in particular the time dependent permittivity of section [ sec : tdp ] which would typically be called a dynamic casimir type effect . in cases of oscillatory motion or material time dependence , pairs of polaritons can be emitted with the total energy of the pair @xmath246 coming from the motion . we have found that so long as energy and momentum are conserved and the energy of both polaritons is positive , there is always some excitation in the material . however , this is typically very small unless the wave vectors and frequencies are close to either a material resonance , or to fulfilling the dispersion relation for electromagnetic waves . the emission from a moving perturbation is of exactly the same form , and from the perspective of the perturbation theory comes from the same ` dynamic casimir ' term ( [ secondterm ] ) . the only difference is that in this case the energy available for the creation of excitations instead comes from the frequencies @xmath247 within the moving perturbation , the @xmath90 dependence of which complicates the functional form of the emission spectral density . the motivation behind this calculation was to understand the effects of the time dependence and motion of dielectric media on the excitations of polaritons ( i.e. the normal modes of light and matter ) , when the effects of dissipation and dispersion are fully taken into account . in particular we analysed the necessary modifications to the hamiltonian of macroscopic qed that must be made to describe the motion and time dependence of a dielectric , and applied this to calculate the polariton excitation rate in the three illustrative cases summarized in figure [ fig : system ] . before calculating this emission rate we briefly discussed that the distinct effect of motion versus time dependence is to introduce non - locality into the permittivity . in the case of uniform translational motion this non - locality is simply the well known doppler shift of the frequency dispersion , but that for more complicated motion becomes increasingly intricate . having found the separate modifications to the hamiltonian of macroscopic qed necessary to describe moving or time dependent dielectric media , we applied time dependent perturbation theory to calculate the emission rate of polaritons in three particular cases . in general we found that so long as the energies of both polaritons are positive , and energy and momentum are conserved then there is always some albeit often very small excitation rate . for a uniform medium performing an oscillatory motion , or material properties that oscillate in time with angular frequency @xmath82 , energy conservation demands that the total energy of the pair equals @xmath246 . for a material with a single resonance at @xmath139 this means that there will be a peak in the emission ( although not the only peak ) when e.g. one of the pair has frequency @xmath139 and wave vector @xmath90 , and the other has frequency @xmath175 and wave vector @xmath191 where @xmath248 is very large ( i.e. close to fulfilling the dispersion relation ) . experimentally it might be of particular importance that in all the cases we examined , the regions where the polaritons both nearly fulfil the dispersion relation and are close to a material resonance contribute most to the emission . the final example we considered was the emission of polariton pairs from a uniformly moving perturbation to the permittivity of a medium . we found that the description of this process is not fundamentally different from that of emission from a uniform time oscillating permittivity . the main difference is that rather than take energy @xmath246 from the oscillation of the material properties , the polaritons take energy @xmath249 from the motion of the perturbation . vector dependence of the energy makes the emission increase with spatially sharper perturbations , and typically causes the polaritons to be emitted in cones . however , the peak emission is still concentrated around the regions where the frequencies where one of the pairs is close to a material resonance , and the other is close to fulfilling the dispersion relation for electromagnetic waves , where both are at resonances , or where both are close to fulfilling the dispersion relation . this finding that a emitted photon may be paired with an excitation of the material at a resonance may be useful for understanding some of the recent experiments on analogue hawking emission in optical media . from @xcite , the coefficients in the expansion of the field operators in terms of the polariton creation and annihilation operators are given by @xmath250\\ & \mathbf{f}_{\mathbf{e}}\left(\mathbf{x},\mathbf{x_{1}},\omega_{1}\right)=\mu_{0}\sqrt{\frac{\hbar}{2\omega_{1}}}\omega_{1}^{2}\alpha_{b}\left(\mathbf{x_{1}},\omega_{1}\right)\mathbf{g}\left(\mathbf{x},\mathbf{x_{1}},\omega_{1}\right)\\ & \mathbf{f}_{\mathbf{a}}\left(\mathbf{x},\mathbf{x_{1}},\omega_{1}\right)=-\frac{i}{\omega}\left[\mathbf{f}_{\mathbf{e}}\left(\mathbf{x},\mathbf{x_{1}},\omega_{1}\right)\right]_{t}\\ & \mathbf{f}_{\mathbf{\pi_{a}}}\left(\mathbf{x},\mathbf{x_{1}},\omega_{1}\right)=-\epsilon_{0}\epsilon_{b}(\mathbf{x},\omega_{1})\mathbf{f}_{\mathbf{e}}\left(\mathbf{x},\mathbf{x_{1}},\omega_{1}\right)-\sqrt{\frac{\hbar}{2\omega_{1}}}\alpha_{b}(\mathbf{x},\omega_{1})\delta^{(3)}(\mathbf{x}-\mathbf{x_{1}})\\ & \mathbf{f}_{\mathbf{\pi_{x}}}\left(\mathbf{x},\mathbf{x_{1}},\omega,\omega_{1}\right)=-i\omega_{1}\mathbf{f}_{\mathbf{x}}\left(\mathbf{x},\mathbf{x_{1}},\omega,\omega_{1}\right ) \end{split}\ ] ] where @xmath251 is an infinitely small number serving to shift the coefficients off the real axis in the complex plane , the subscript @xmath147 denotes the transverse components , and the green function obeys @xmath252 with the boundary condition that the waves are outgoing at infinity ( i.e. the retarded green function ) . for the case of an infinite homogeneous medium with permittivity @xmath138 , the solution to ( [ eq : greensfourier ] ) is given by @xmath253 where a positive imaginary part for @xmath254 $ ] picks out the retarded green function . for the case of a infinite homogeneous oscillating medium of section [ homed ] , the rate of change amplitude @xmath160 is @xmath255\ ] ] where the quantity @xmath256 is given by @xmath257 + b\left(\omega_{1},\omega_{2}\right)\mathbf{g}^{*}\left(\mathbf{-k},\omega_{2}\right)+c\left(\omega_{1},\omega_{2}\right)\mathbf{g}^{\dagger}\left(\mathbf{k},\omega_{1}\right)+d\left(\omega_{1},\omega_{2}\right)\mathbb{1}_{3 } \\[5pt ] + e\left(\omega_{1},\omega_{2}\right)\frac{1}{k_{z } } \left(\mathbf{g}^{\dagger}\left(\mathbf{k},\omega_{1}\right)\times\mathbf{k}\right)\cdot\left(\mathbf{\hat{z}}\times\mathbb{1}_{3}\right)\cdot\left(\chi\left(\omega_{2}\right)\frac{\omega_{2}^{2}}{c^{2}}\mathbf{g}^{*}\left(-\mathbf{k},\omega_{2}\right)+\mathbb{1}_{3}\right)\end{gathered}\ ] ] with the coefficients within this quantity given as @xmath258 we wish to evaluate the limit @xmath259 where @xmath260 . performing the integral and taking the limit yields @xmath261-\cos\left[\left(\omega_{1}+\omega_{2}\right)t\right]}{\left[\left(\omega_{1}+\omega_{2}\right)^{2}-\nu^{2}\right]t}\right ) \end{split}\ ] ] where the first two terms are derived in the same way as ( [ eq : timedep ] ) . the third can be evaluated by considering that it will eventually be convoluted with a function of @xmath120 such as @xmath262-\cos\left[\left(\omega_{1}+\omega_{2}\right)t\right]}{\left[\left(\omega_{1}+\omega_{2}\right)^{2}-\nu^{2}\right]t}.\ ] ] over the the range @xmath263 , only a small region will contribute to the integral when @xmath147 is large , namely the region around @xmath264 . this integral is therefore equivalent to the following expression @xmath265-\cos\left[\left(\nu+\eta\right)t\right]}{\left[\left(\nu+\eta\right)^{2}-\nu^{2}\right]t}.\ ] ] for large @xmath147 , @xmath266 will be small and as such we can treat @xmath267 as small and make the following approximation @xmath268}{2\nu}.\ ] ] in the limit @xmath148 , the range @xmath269 and as such the area under the integral above vanishes . we can thus ignore the third term of equation ( [ eq : deltaapp2 ] ) . h. b. g. casimir,_koninkl . proc . _ * 51 * , 793 ( 1948 ) . t. g. philbin , _ new j. phys . _ * 13 * 063026 , ( 2011 ) . l. d. landau , e. m. lifshitz and l. p. pitaevskii , _ electrodynamics of continuous media _ , butterworth - heinemann , ( 1984 ) . a. i. volokitin and b. n. j. persson , _ phys . * 106 * , 094502 ( 2011 ) . t. g. philbin and u. leonhardt , _ new j. phys _ * 11 * , 033035 ( 2009 ) . j. b. pendry , _ j. phys . cond .. matter _ * 9 * , 10301 ( 1997 ) . t. g. phlibin , c. kuklewicz , s. robertson , s. hill , f. knig and u. leonhardt , _ science _ * 319 * , 1367 ( 2008 ) . s. m. hawking , _ nature _ * 248 * , 30 ( 1974 ) . s , weinfurtner , e. w. tedford , m. c. j. penrice , w. g. unruh and g. a. lawrence , _ phys . lett . _ * 106 * , 021302 ( 2011 ) . f. belgiorno , s. l. cacciatori , m. clerici , v. gorini , g. ortenzi , l. rizzi , e. rubino , v. g. sala and d. faccio , _ phys . lett . _ * 105 * , 203901 ( 2010 ) . d. faccio , _ clas . * 29 * , 224009 ( 2012 ) . j. b. pendry , _ new j. phys . _ * 12 * 068002 ( 2010 ) . u. leonhardt , _ new j. phys . _ * 12 * 068001 ( 2010 ) . j. j. hopfield , _ phys . _ * 122 * 1555 ( 1958 ) . b. huttner , s. m. barnett,_phys . rev . _ a * 46 * 4306 , ( 1992 ) . l. g. suttorp and m. wubs , _ phys . rev . _ a * 70 * , 013816 ( 2004 ) . s. scheel and s. y. buhmann , _ acta physica solvaca _ * 58 * , 675 ( 2008 ) . m. amooshahi and f. kheirandish,_j phys . _ a * 41 * , 275402 ( 2008 ) . t. g. philbin , _ new j. phys . _ * 12 * , 123008 ( 2010 ) . s. a. r. horsley , _ phys . rev . _ a * 84 * , 063822 ( 2011 ) . s. a. r. horsley , _ phys . rev . _ a * 86 * , 023830 ( 2012 ) . v. v. dodonov , _ physica scripta _ * 82 * 038105 ( 2010 ) . c. m. wilson , g. johansson , a. pourkabirian , j. r. johansson , t. duty , f. nori and p. delsing,_nature _ * 479 * , 376 ( 2011 ) . i. e. dzyaloshinskii , e. m. lifshitz and l. p. pitaevskii , _ sov . uspekhi _ * 4 * 153 ( 1961 ) . g. b. arkfen , h. j. weber and f. e. harris , _ mathematical methods for physicists _ , elsevier ( 2013 ) . s. weinberg , _ the quantum theory of fields _ , cambridge university press ( 1995 ) . s. a. fulling , p. c. w. davies,_proc . roy . soc . _ a * 348 * , 393 ( 1975 ) . v. b. berestetskii , e. m. lifshitz and l. p. pitaevskii , _ quantum electrodynamics _ , butterworth - heinemann ( 2008 ) .
in recent years , a rigorous quantum mechanical model for the interaction between light and macroscopic dispersive , lossy dielectrics has emerged macroscopic qed allowing the application of the usual methods of quantum field theory . here , we apply time dependent perturbation theory to a general class of problems involving time dependent lossy , dispersive dielectrics . the model is used to derive polariton excitation rates in three illustrative cases , including that of a travelling gaussian perturbation to the susceptibility of an otherwise infinite homogeneous dielectric , motivated by recent experiments on analogue hawking radiation . we find that the excitation rate is increased when the wave vector and frequency of each polariton in the pair either satisfies ( or nearly satisfies ) the dispersion relation for electromagnetic waves , or is close to a material resonance .
a domain @xmath0 is called a _ quadrature domain _ if it admits a formula for the integration of any harmonic and integrable function @xmath1 in @xmath2 , @xmath3 where @xmath4 is a distribution ( independent of @xmath5 ) such that @xmath6 . in particular , when @xmath4 is a measure , then by applying ( [ eq : qfgen ] ) to the newtonian kernel it results that the external potential of the body @xmath2 with density one is equal to the potential of the measure @xmath4 . if @xmath4 is a finitely - supported distribution of finite - order ( so the right - hand - side of ( [ eq : qfgen ] ) is a finite sum of weighted point evaluations of @xmath5 and its partial derivatives ) , then @xmath2 is referred to as a _ quadrature domain in the classical sense_. there are many examples of quadrature domains in the classical sense in the plane , where conformal mappings can be used to construct them ( see e.g. @xcite ) . but in higher dimensional spaces , very few explicit examples are known @xcite , and the only known explicit example involving simple point evaluations ( with no partial derivatives appearing ) is the ball . there are however existence results for such quadrature domains @xcite . one of the simplest non - trivial examples of a quadrature domain ( in the classical sense ) in the plane is the region whose boundary is described by the real algebraic curve ( excluding the origin ) : @xmath7 this curve is referred to as neumann s oval ( it is also known as the hypopede of booth ) . denoting this region by @xmath2 , the quadrature formula is a sum of two point evaluations : @xmath8 where the coefficient @xmath9 is a function of @xmath10 and @xmath11 . this quadrature identity was discoved by c. neumann in 1908 @xcite , see ( * ? ? ? * ch . 5 , 14 ) or ( * ? ? ? 3 ) for details . more generally , we refer to a domain @xmath0 as a _ neumann ovaloid _ if it admits a quadrature formula having two quadrature nodes with equal weights . we will consider the case of a four - dimensional neumann ovaloid @xmath12 satisfying : @xmath13 for some positive constant @xmath14 . as one should expect , @xmath2 is axially - symmetric ( see the next paragraph below ) . however , the axially - symmetric domain in @xmath15 generated by the rotation of a two - dimensional neumann oval is not a neumann ovaloid , and in fact , it is not even a quadrature domain in the classical sense . instead , as the first author showed in @xcite , it has a quadrature formula supported on the whole segment joining the original quadrature points . concerning uniqueness , suppose that the distribution @xmath4 of ( [ eq : qfgen ] ) is a non negative measure with compact support in a hyperplane , as in the case of interest ( [ eq : qf ] ) . if @xmath2 is a bounded quadrature domain for @xmath4 , then @xmath2 is symmetric with respect to the same hyperplane and the complement of the closure of @xmath2 is connected . this result was proved by sakai in the plane @xcite , and for the @xmath16-dimensional case see @xcite . we may apply this to every hyperplane passing through the two quadrature points in order to conclude that the neumann ovaloid @xmath2 is axially symmetric since the neumann ovaloid @xmath2 is axially symmetric and has connected complement of its closure , it must be generated by rotation of a simply connected planar domain @xmath17 . invoking the riemann mapping theorem , there is a conformal map @xmath18 from the unit disk @xmath19 to @xmath17 , and @xmath18 is unique once the value of @xmath20 and @xmath21 are prescribed . in order to construct @xmath2 , it thus suffices to determine explicitly the conformal map @xmath18 . [ thm : neumannovaloid ] let @xmath22 be the quadrature domain that satisfies the formula ( [ eq : qf ] ) , and let @xmath17 denote the simply connected domain that generates @xmath2 by rotation . let @xmath18 be the conformal map from the unit disk @xmath19 to @xmath17 such that @xmath23 and @xmath24 . then @xmath18 is given by : @xmath25 for some real - valued positive constants @xmath26 and @xmath27 . there are existence results for point mass quadrature domains @xcite ; the important attribute of theorem [ thm : neumannovaloid ] is the explicit formula for the domain . for each @xmath11 and @xmath14 , the neumann ovaloid ( [ eq : qf ] ) is unique , this follows from the uniqueness of bounded quadrature domains for non negative measures with compact support in a hyperplane ( see @xcite ) . in section [ sec : prelim ] , we review some essential background on axially symmetric quadrature domains in @xmath15 following @xcite . we prove theorem [ thm : neumannovaloid ] in section [ sec : main ] . the proof is based on the approach introduced in @xcite where a. eremenko and the second author used it to give a negative answer to the question of h.s . shapiro @xcite on the algebraicity of quadrature domains in @xmath28 dimensions . in section [ sec : constants ] we describe how @xmath29 and @xmath30 of formula ( [ eq : conf ] ) are related when @xmath31 is fixed , and we show that the quadrature formula for the ball is recovered from ( [ eq : qf ] ) in the limit as @xmath29 and @xmath30 tend to zero . in section [ sec : numerical ] , we present some graphics based on numerical implementation of theorem [ thm : neumannovaloid ] . here we review an algebraic technique that applies to axially symmetric quadrature domains in @xmath32 . for further details see @xcite . an equivalent definition of the quadrature domain ( [ eq : qfgen ] ) is by the free boundary problem @xmath33 the two notions are equivalent when the domain @xmath34 is bounded and the distribution @xmath4 is compactly supported in @xmath2 . a solution @xmath5 to the overdetermined system ( [ eq : sp ] ) is called the _ schwarz potential _ of @xmath2 . in the case of the neumann ovaloid ( [ eq : qf ] ) , the distribution @xmath4 , as well as the domain @xmath2 has axial symmetry about the @xmath35axis . hence the schwarz potential @xmath5 can be represented by a function of two variables , namely @xmath36 where @xmath37 and @xmath38 for negative @xmath39 . then the function @xmath40 satisfies the free boundary problem @xmath41 where @xmath42 is the domain whose rotation generates @xmath2 . the main idea is to set @xmath43 , then @xmath44 satisfies the cauchy problem @xmath45 this enables us to solve the free boundary problem ( [ eq : free - b ] ) by means of the schwarz function . indeed , letting @xmath46 and @xmath47 , then on the boundary @xmath48 , @xmath49 where @xmath50 . next , we replace @xmath51 by @xmath52 on the boundary @xmath48 , and we obtain @xmath53 as the solution to the cauchy problem ( [ eq : cauchy ] ) ( see ( * ? ? ? * lemma 2.3 ) ) . the representation of the solution @xmath44 by ( [ eq : int ] ) implies that the singularities of @xmath54 determine the distribution @xmath4 in ( [ eq : sp ] ) . since we are interested only in the structure of the distribution @xmath4 , we may perturb this expression by a holomorphic function . thus we conclude that the singularities of the expression @xmath55 govern the distribution @xmath4 . due to the axial symmetry , the support of the distribution @xmath4 is on the @xmath56axis . so if the expression in ( [ eq:9 ] ) has non vanishing residue at the points @xmath57 , then in the integration ( [ eq : int ] ) causes to a logarithmic term and consequently the support of @xmath4 is on a segment joining these two points . this implies that @xmath2 will not be point masses quadrature domain . for example , if @xmath17 is the neumann oval ( [ eq : neumannoval ] ) , then @xmath58 where @xmath59 is holomorphic in @xmath17 . however , if we require that @xmath60 then @xmath61 with @xmath62 harmonic in @xmath17 . recalling that @xmath63 , we see that the singular part of the schwarz potential ( [ eq : sp ] ) comprises the expression @xmath64 , which is the fundamental solution of the laplacian in @xmath15 at the points @xmath65 . hence @xmath66 is the distribution of the schwarz potential ( [ eq : sp ] ) and consequently the rotation of @xmath17 yields the neumann ovaloid ( [ eq : qf ] ) , here @xmath67 denote the dirac measure . as in the statement of theorem [ thm : neumannovaloid ] , take @xmath18 to be the conformal map from the unit disk @xmath19 into @xmath17 such that @xmath68 and @xmath69 is real . with this normalization , the conformal map is unique . by symmetry of the domain @xmath17 under complex conjugation , and uniqueness of the conformal map , @xmath18 is real , i.e. , @xmath70 . let @xmath71 be the schwarz function of the boundary @xmath48 . following @xcite , we consider the pullback of ( [ eq : schwarz ] ) under the conformal map @xmath18 . using the relation @xmath72 we have @xmath73 setting @xmath74 then obviously @xmath75 . using this fact , we can use ( [ eq : pullback ] ) to analytically continue @xmath76 to the entire plane as a meromorphic ( and in fact rational ) function . namely , we prove the following : [ lem:1 ] the function @xmath77 is a rational function of degree exactly @xmath78 and takes the form : @xmath79 with @xmath29 , @xmath30 , @xmath80 real constants and @xmath81 . the points @xmath82 are the preimages of @xmath83 under @xmath18 . from ( [ eq : pullback ] ) @xmath77 has a pole of order two at @xmath84 and no other poles in @xmath19 . since @xmath85 , @xmath77 has also poles of order two at @xmath86 . there are no other poles in @xmath87 , since otherwise we would have a contradiction to ( [ eq : schwarz ] ) . thus , @xmath77 is a meromorphic function in the entire plane with exactly four poles of order two . if @xmath88 , then the conformal map @xmath89 as @xmath90 , and that would imply that the schwarz function has a pole at the origin , which contradicts ( [ eq : schwarz ] ) . this implies @xmath77 is a rational function of degree exactly @xmath78 . having determined the location of the poles , we have @xmath91 where @xmath92 is a polynomial of degree @xmath78 . from ( [ eq2 ] ) we see that @xmath93 and the zeros have order two . hence @xmath77 has additional four zeros . so suppose @xmath94 is a zero of @xmath77 , then @xmath95 since @xmath96 . note that @xmath97 , which follows from the symmetry of @xmath17 with respect to the real and imaginary axes , hence @xmath98 is a zero of @xmath77 , and by ( [ eq2 ] ) @xmath77 vanishes @xmath99 . thus @xmath100 now set @xmath101 and @xmath102 for some positive @xmath29 , then @xmath103 since @xmath104 , @xmath77 is non negative on the real axis . hence the above expression is real , and therefore @xmath105 which results in the identity @xmath106 thus either @xmath107 or @xmath108 or @xmath109 . note that @xmath107 is impossible since then @xmath110 would have branch points on the unit circle and consequently @xmath18 is not single valued . if @xmath111 , then @xmath112 is negative for some @xmath113 when @xmath114 . hence @xmath109 and then @xmath115 thus @xmath116 , and we have @xmath117 and we have obtained ( [ eq : lemma ] ) . applying the lemma [ lem:1 ] , and taking the square root in equation ( [ eq2 ] ) we have : @xmath118 where @xmath119 . multiplying by @xmath120 and integrating with respect to @xmath121 along the contour @xmath122 , we obtain @xmath123 the term @xmath124 integrates to zero since it is analytic in @xmath87 and @xmath125 since @xmath126 is analytic in @xmath19 , we may apply the cauchy integral formula : @xmath127 thus we have : @xmath128 and this completes the proof of theorem [ thm : neumannovaloid ] . notice that the quadrature domain depends on only two parameters , @xmath11 and @xmath14 , while the conformal map @xmath18 appears to depend on three real parameters , @xmath129 , @xmath130 , and @xmath131 . however , fixing @xmath132 , the value of @xmath29 is determined by the value of @xmath30 . in this section , we fix @xmath31 , which gives that @xmath18 is the identity map when @xmath133 . we will show how parameters @xmath29 and @xmath30 are related and also show that as @xmath29 and @xmath30 tend to zero , we recover the quadrature formula for the unit ball . notice that equation ( [ eq : schwarz ] ) provides a constraint relating @xmath29 and @xmath30 . namely , we observe that the residue of @xmath134 at @xmath135 vanishes , which is equivalent to @xmath136 . since the pole is of order two , we have : @xmath137 setting @xmath138 then by the formula of @xmath139 ( [ eq : conf ] ) , @xmath140\sqrt{g(w ) } dw \\ & = : f(a , b ) . \end{split}\ ] ] thus we conclude that the rotation of the domain @xmath17 generates the neumann ovaloid ( [ eq : qf ] ) if and only if @xmath141 for some positive @xmath29 and @xmath30 . we shall use the implicit function theorem in order to justify that identity ( [ eq : res:2 ] ) determines the parameter @xmath29 as a function of @xmath30 . to this end , the expressions @xmath142 and @xmath143 can be computed using symbolic computation software : @xmath144 @xmath145 it follows from the above computations the functional @xmath146 is not continuous when @xmath147 . hence , we set @xmath148 and @xmath149 then obviously @xmath141 for @xmath150 if and only if @xmath151 . we shall now compute the taylor expansion of @xmath152 near the origin . from ( [ eq : com:1 ] ) and ( [ eq : com:2 ] ) we see that @xmath153 hence @xmath154 and @xmath155 since both @xmath156 and @xmath157 are of order @xmath158 for @xmath30 near zero , @xmath159 and @xmath160dw + o(b^2 ) . \end{split}\ ] ] from ( [ eq : com:1 ] ) and ( [ eq : com:2 ] ) we that @xmath161 and + @xmath162 , hence @xmath163 in a similar manner we have computed @xmath164 ( see appendix [ appendix ] ) , hence @xmath165 thus by the implicit function theorem there is a function @xmath166 such that @xmath167 for @xmath30 near zero and positive . moreover , we see from ( [ eq : com:3 ] ) that @xmath168 . hence the functional @xmath146 , which is defined by ( [ eq : res:2 ] ) , vanishes near the origin on a curve , in which @xmath169 , or more precisely @xmath170 the coefficient @xmath14 of the quadrature identity ( [ eq : qf ] ) can be computed as follows . when @xmath141 , then ( [ eq : schwarz ] ) holds and therefore by ( [ eq : pullback ] ) @xmath171 writing @xmath172 , where @xmath173 , then by lemma [ lem:1 ] , @xmath174 the estimate ( [ eq : asym ] ) enables us to examine the asymptotic behavior as @xmath175 goes to zero . we see that @xmath176 and since when @xmath177 , the conformal mapping @xmath18 tends to the identity , we conclude that @xmath178 . on the other hand , letting @xmath11 tend to zero in ( [ eq : qf ] ) , then the right hand side goes to @xmath179 , and the domain @xmath2 tends to the unit ball . hence the limit coincides with the mean value property of harmonic functions . numerical implementation of theorem [ thm : neumannovaloid ] requires determining appropriate choices of parameters . the parameter @xmath27 simply scales the domain , so that there is only a one - parameter family of different shapes . while varying the choice of @xmath30 , we choose @xmath29 to satisfy the relation ( [ eq : res:1 ] ) this is done numerically using matlab . we then use the condition @xmath180 ( where @xmath27 appears as a scalar ) in order to choose @xmath27 so that @xmath181 . this leads to a one - parameter family of different shapes having the same `` foci '' @xmath182 . we note that this family can also be interpreted as a four - dimensional hele - shaw flow with two point sources ( located at the foci ) . we used matlab to perform numerical integration of the cauchy transform appearing in ( [ eq : conf ] ) . this requires some care in checking that the branch of the square root is defined appropriately . the radius of the contour of integration should also be increased slightly ( without crossing any singularities of the integrand ) ; this is a convenient way to avoid numerically integrating through the simple pole presented by the fact that @xmath183 is on the unit circle . having carried out these steps , we display some images of the profile curves for the resulting confocal neumann ovaloids in figure [ fig : neumann ] . obtained as a numerical cauchy transform . ] here we shall provide further details for the computations of the second order derivatives @xmath184 and @xmath185 . from the expressions ( [ eq : com:1 ] ) and ( [ eq : com:2 ] ) we see that @xmath186dw\\ & + \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}\left[\left(\frac{1 + b^2(-8\delta+4)}{-4(w - b)^2}+2\frac{b}{4(w - b)^3}\right)\right . \\ & \times \left.\frac{(w^2 - 1)\sqrt{(w^2+\delta)(1+w^2\delta ) } } { ( w^2-b^2)(1-w^2b^2)}\right]dw + o(b^2 ) \end{split}\ ] ] letting @xmath187 and recalling that @xmath188 , we see that @xmath189dw \\ & + \frac{1}{4}+o(b^2)\\ = & \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}\left[\left(\frac{2b}{4(w - b)^3}\right ) \frac{(w^2 - 1)w}{(w^2-b^2)(1-w^2b^2)}\right]dw \\ + & \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}\frac{1}{4}\left[(w^2 - 1)w\left(\frac{1}{w^4}- \frac{1}{(w - b)^2(w^2-b^2)(1-w^2b^2)}\right)\right]dw \\ & + o(b^2 ) . \end{split}\ ] ] in the last equality we used the fact that @xmath190 by taylor expansion , @xmath191 and hence @xmath192dw -\frac{1}{2\pi i}\int\limits_{\{|w|=1\}}\left[\left(\frac{2(w^2 - 1)w}{4w^5}\right ) \right]dw\\ & = 0 . \end{split}\ ] ] we turn now to the computation of @xmath193 . using ( [ eq : app:2 ] ) and ( [ eq : app:1 ] ) , we have that @xmath194dw\\ + & \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}-\frac{1}{4 } \left[\frac{(w^2 - 1)\sqrt{(w^2+\delta)(1+w^2\delta ) } } { w^4}\right]dw + \frac{1}{4}\\ = & \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}-\frac{1}{8 } \left[\frac{\delta(w^2 - 1)(1 + 2\delta w^2+w^4)}{w^4\sqrt{(w^2+\delta)(1+w^2\delta)}}\right]dw\\ + & \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}\frac{1}{4 } \left[\frac{(w^2 - 1)w}{w^4}\left(1-\sqrt{1+\delta\left(\frac{1}{w^2}+w^2\right ) + \delta^2}\right)\right]dw . \end{split}\ ] ] taylor expansion @xmath195 yields that @xmath196dw\\ + & \frac{1}{2\pi i}\int\limits_{\{|w|=1\}}\frac{1}{8 } \left[\frac{(w^2 - 1)w}{w^4}\left(\frac{1}{w^2}+w^2\right)\right]dw\\ = & \frac{1}{8}-\frac{1}{8}=0 . \end{split}\ ] ] c. neumann , _ ber das logarithmische potential einer gewissen ovalflche _ , . klasse der knigl . zu leibzig * 60 * ( 1908 ) , 5356 . dritte mitteilung , ibid . 240247 .
what is the shape of a uniformly massive object that generates a gravitational potential equivalent to that of two equal point - masses ? if the weight of each point - mass is sufficiently small compared to the distance between the points then the answer is a pair of balls of equal radius , one centered at each of the two points , but otherwise it is a certain domain of revolution about the axis passing through the two points . the existence and uniqueness of such a domain is known , but an explicit parameterization is known only in the plane where the region is referred to as a neumann oval . we construct a four - dimensional `` neumann ovaloid '' , solving explicitly this inverse potential problem .
SHARE THIS ARTICLE Share Tweet Post Email As investigators prepare to concede defeat in their search for Malaysia Airlines Flight 370, some scientists are pondering the unthinkable: they’ve been looking in the wrong place for more than two years. Ships scouring an almost endless expanse of southern Indian Ocean have whittled down the area to a patch little bigger than the U.S. state of Delaware. They’ve turned up nothing of the jet that disappeared March 8, 2014, en route to Beijing from Kuala Lumpur with 239 people on board. With no closure in sight, transport ministers from Malaysia, China and Australia meet Thursday in Kuala Lumpur to assess the A$180 million ($135 million) operation. There are no plans to look beyond the designated 120,000 square kilometers (46,330 square miles), the Australian Transport Safety Bureau said in an e-mail before today’s meeting. More than 90 percent of the search area has already been covered. The absence of wreckage in the search area to date may question one of the recovery mission’s central assumptions -- that no one was in control of the plane when it ran out of fuel and spiraled sharply into the ocean, said Vaughan Clarkson, a former University of Queensland radar and tracking specialist and one of the scientists who helped recreate MH370’s flight path for the Australian government. Rather, the fruitless hunt suggests someone glided the aircraft into the water -- beyond what would become the outer limits of the search zone, he said. Leidschendam, Netherlands-based Fugro NV is the contractor carrying out the search operations. “Probably what we’ve discovered from this exercise is that the plane was under active control,” said Clarkson, who’s now an independent consultant. “The search area must be basically right, but perhaps it’s not quite big enough.” The implications of a controlled glide into the ocean are vast. Even with no fuel, a pilot could have guided MH370 for a further 230 kilometers, the ATSB said in a December 2015 report. That’s more than enough to reach Philadelphia from New York. It could mean combing an area almost as big as California for the best part of a decade. For a related story, click: Missing Malaysia Jet Weeks Away From Keeping Secrets Forever If the assumptions were accurate, there’s little chance the wreck could remain hidden in the search area, Australian government scientists said in a report last year. At depths of up to 6 kilometers (4 miles), the underwater search has been so thorough that not even lumps of coal on the seabed have escaped detection, the ATSB said in an e-mail to Bloomberg News this week. Recreating Flight 370’s last moments has always been one of the biggest challenges. Earlier satellite data from the plane suggested it cruised south over the Indian Ocean for about six hours. And a final automated electronic message probably coincided with fuel exhaustion, scientists concluded. But after that, scientists had little help other than flight simulations and data from old plane crashes. Air-traffic controllers lost contact with MH370 less than an hour after takeoff as it approached Vietnam. Malaysia Prime Minister Najib Razak has said the plane was deliberately steered off course. Step Back After an effective but fruitless search of this nature, it may be time to step back and reevaluate, Larry Stone, the chief scientist at Reston, Virginia-based consultant Metron Inc. who has tracked missing aircraft and ships for half a century, said in an e-mail. “You have effectively exhausted the information on which your search was planned,” said Stone, who mapped out the resting place of Air France Flight 447, which was recovered two years after plummeting into the Atlantic Ocean with 228 people aboard in 2009. One option is to revise the assumptions on which the search is based and question whether neglected information should be included in a new hunt, Stone said in an email. Families of the passengers are already petitioning for the search to be extended. Wild winter weather and waves more than five stories high have delayed the mission in the Indian Ocean. An original mid-year completion target has been pushed back by up to eight weeks, investigators said in a July 13 update. The first debris from MH370 was found on Reunion Island in July 2015. Four other pieces that turned up on Africa’s eastern seaboard and in Mauritius almost certainly belong to the doomed jet, according to investigators. Officials are also analyzing a possible wing flap found late June on Pemba Island off the coast of Tanzania. Investigators haven’t yet confirmed that the debris belongs to MH370. Ultimately, the decision by ministers in Kuala Lumpur may boil down to time and money. “My own feeling is that it would be a shame if we let the search drop,” said tracking specialist Clarkson. “But I appreciate that a hard-headed decision needs to be made at some point.” ||||| Flight officer Rayan Gharazeddine looks out of a Royal Australian Air Force (RAAF) AP-3C Orion as it flies over the southern Indian Ocean during the search for missing Malaysian Airlines flight MH370 March 22, 2014. REUTERS/Rob Griffith/Pool/File Photo SYDNEY (Reuters) - Top searchers at the Dutch company leading the underwater hunt for Malaysia Airlines jet MH370 say they believe the plane may have glided down rather than dived in the final moments, meaning they have been scouring the wrong patch of ocean for two years. Flight MH370 disappeared in March 2014 with 239 passengers and crew onboard en route to Beijing from Kuala Lumpur. Searchers led by engineering group Fugro (FUGRc.AS) have been combing an area roughly the size of Greece for two years. That search, over 120,000 square kilometers of the southern Indian Ocean off Western Australia, is expected to end in three months and could be called off after that following a meeting of key countries Malaysia, China and Australia on Friday. The three countries agreed in April 2015 that should the aircraft not be located within the search area, and in the absence of any new credible evidence, the search area would not be extended. So far, nothing has been found. “If it’s not there, it means it’s somewhere else,” Fugro project director Paul Kennedy told Reuters. Kennedy does not exclude extreme possibilities that could have made the plane impossible to spot in the search zone, and still hopes to find the craft. But he and his team argue another option is the plane glided down - meaning it was manned at the end - and made it beyond the area marked out by calculations from satellite images. “If it was manned it could glide for a long way,” Kennedy said. “You could glide it for further than our search area is, so I believe the logical conclusion will be well maybe that is the other scenario.” Doubts that the search teams are looking in the right place will likely fuel calls for all data to be made publicly available so that academics and rival companies can pursue an “open source” solution - a collaborative public answer to the airline industry’s greatest mystery. Fugro’s controlled glide hypothesis is also the first time officials have leant some support to contested theories that someone was in control during the flight’s final moments. Since the crash there have been competing theories over whether one, both or no pilots were in control, whether it was hijacked - or whether all aboard perished and the plane was not controlled at all when it hit the water. Adding to the mystery, investigators believe someone may have deliberately switched off the plane’s transponder before diverting it thousands of miles. The glide view is not supported by the investigating agencies: America’s Boeing Co (BA.N), France’s Thales SA (TCFP.PA), U.S. investigator the National Transportation Safety Board, British satellite company Inmarsat PLC(ISA.L), the U.K. Air Accidents Investigation Branch and the Australian Defence Science and Technology Organisation. Australian and Malaysian officials examine aircraft debris at the Australian Transport Safety Bureau headquarters in Canberra, Australia, July 20, 2016 after it was found on Pemba Island, located near Tanzania, in late June and was transported to Australia for examination. Australian Transport Safety Bureau/Handout via REUTERS CARRY ON The meeting between officials from China, Australia and Malaysia is expected to discuss the future of the search. The three governments have previously agreed that unless any new credible evidence arises the search would not be extended, despite calls from victims’ families. Any further search would require a fresh round of funding from the three governments on top of the almost A$180 million ($137 million) that has already been spent, making it the most expensive in aviation history. Deciding the search area in 2014, authorities assumed the plane had no “inputs” during its final descent, meaning there was no pilot or no conscious pilot. They believe it was on auto-pilot and spiraled when it ran out of fuel. Slideshow (3 Images) But Kennedy said a skilled pilot could glide the plane approximately 120 miles (193 km) from its cruising altitude after running out of fuel. One pilot told Reuters it would be slightly less than that. For the aircraft to continue gliding after fuel has run out, someone must manually put the aircraft into a glide – nose down with controlled speed. “If you lose all power, the auto-pilot kicks out. If there is nobody at the controls, the aircraft will plummet down,” said a captain with experience flying Boeing 777s - the same as MH370. Like all pilots interviewed for this story, he declined to be named given the controversy around the lost jet. Fugro works on a “confidence level” of 95 percent, a statistical measurement used, in Fugro’s case, to indicate how certain the plane debris was not in the area they have already combed, a seabed peppered with steep cliffs and underwater volcanoes. “The end-of-flight scenarios are absolutely endless,” Fugro managing director Steve Duffield said. “Which wing ran out of fuel first, did it roll this way or did it tip that way?” The Australian Transport Safety Bureau (ATSB), the agency coordinating the search, has consistently defended the defined search zone. It did not immediately respond to questions over whether it was assessing the controlled glide theory. Authorities used data provided by Inmarsat to locate the likely plunge point through communication between the plane and satellite ground station. “All survey data collected from the search for missing flight MH370 will be released,” an ATSB spokesman said.
– Roughly 15 months ago, Malaysia, China, and Australia decided that if they couldn't find the wreckage of Flight MH370 in the designated search area—a portion of the southern Indian Ocean the size of Greece, reports Reuters—that that would basically be it: no expansion of the area unless concrete evidence indicated they should do so. Nothing has been found since that April 2015 decision, but there is a new theory, from the search team led by Dutch engineering group Fugro. Project director Paul Kennedy tells Reuters it's possible the plane, which vanished while traveling from Beijing from Kuala Lumpur with 239 board, was manned at the very end. That would change its trajectory, with the plane not diving but gliding—for a distance as long as 120 miles, says Kennedy—into the water after its fuel had run out. The working theory has been that there was no one at the wheel during its final descent, and Reuters identifies Kennedy's comments as the first time officials involved in the search have suggested otherwise. Bloomberg reports Malaysia, China, and Australia are meeting Thursday to discuss the status of the search, which has thus far covered more than 90% of the designated search area. Getting behind the new theory "could mean combing an area almost as big as California for the best part of a decade," explains Bloomberg. As for the possibility the searchers just missed the plane's wreckage, the Australian Transport Safety Bureau said in an email the search has been so precise even lumps of coal on the ocean floor have been identified.
an increasing number of large area astronomy surveys that probe time - variable phenomena are producing candidates that need rapid response follow - up ( whether monitoring ongoing changes , or spectroscopic observations to probe physical characteristics ) . salient examples are : the lick observatory supernova search@xcite , the catalina real - time transient survey@xcite , the panoramic survey telescope & rapid response system ( pan - starrs)@xcite , the palomar transient factory ( ptf and iptf)@xcite , and the la silla - quest variability survey@xcite . these surveys are discovering new transient phenomena that are already taxing the available follow - up capacity of telescope facilities world - wide . these projects have developed tools to filter their discoveries to focus on events of interest to their research teams ( e.g. , supernovae , gamma - ray burst events , and so on ) , which can gather ancillary information about their ` alerts ' from external catalogs , and use the available information to classify the sources associated with their alerts . a leading example of this is skyalert@xcite , a system that has solved many of the astronomical issues associated with adding value to alerts . skyalert enables users to create filters on alerts , including ancillary information on these alerts , in order to find relevant events . the ptf system also employs tools to identify interesting alerts @xcite . the scale of time - domain alert generation , though , is quickly increasing . the zwicky transient facility @xcite ( ztf ) will have more than 6 times the field - of - view of ptf , while time domain surveys with decam on the blanco telescope benefit not only from the 3 deg@xmath0 field - of - view , but the depth attainable with a 4m - class facility . moreover , transients are generated across the electromagnetic spectrum , from radio facilities such as lofar to high - energy space - based observatories such as fermi@xcite , making the overall problem that much more complex . on the horizon for beginning operation in 2021 , is the large synoptic survey telescope @xcite . with its 10 deg@xmath0 field - of - view and @xmath16 m collecting area , the transient detection rate leaps by orders of magnitude . lsst will detect ( with 5@xmath2 significance ) @xmath3 alerts per image , or @xmath4 per night . by going fainter , and covering an area of over 18,000 square degrees , this 10 year long survey will probe an unprecedented volume of space with a time cadence that can identify variability on time scales from tens of minutes to years . during the survey operation , the lsst facility will issue alerts of celestial transient events using voevent and other ivoa protocols@xcite . an alert is a notice triggered when an image shows that something is significantly different with respect to an archive image . a variable star may trigger an alert each and every time it is imaged : a supernova in a distant galaxy will trigger repeatedly against an archive image from before it erupted . a moving object will be seen typically over erstwhile blank sky , and move to a different location at subsequent epochs , triggering alerts at all these different locations at each respective epoch . while most alerts will be yet another incremental data point for a celestial object already known to vary , among these multitudes will lurk objects the likes of which have never ( or extremely rarely ) been seen before . prompted by the potential importance of early detection of short lived transient phenomena , the lsst survey will issue alerts with a latency of only about a minute . an alert contains essential information like the location on the sky , the passband in which the variability was detected , whether the change was in brightness or in position , the magnitude of the change , and the epoch of that particular trigger . it may or may not ( depending on the facility that issues it ) contain ancillary information about whether it is a recurrent alert , a history of all alerts at that location in the sky , or other similar ancillary information . a good fraction of alerts from lsst will be known variable stars or moving objects @xcite , but hidden among them will be rare and interesting objects that have relatively short lifetimes . only with additional follow - up will these objects reveal their nature . these could range from short - lived phases of stellar evolution such as the final helium flash @xcite to superluminous supernovae @xcite to electromagnetic counterparts of ligo detections @xcite . beyond these rare , but known or predicted , objects lies the great discovery space that awaits lsst . the superluminous supernovae were essentially unknown fifteen years ago and the discovery of dark energy was certainly surprising . over its life , lsst will generate more than a billion alerts and some will be completely unknown and unanticipated objects . without the ability to rapidly sort through millions of alerts each night and winnow them down to a reasonable number that can be studied in detail , we will lose these rare and potentially extraordinarily interesting objects . the astronomical community is becoming more aware of the necessity of such a tool @xcite . we take note of ( and are encouraged by ) advanced methods for determining classification probabilities using small numbers of time - series measurements ( for instance @xcite ) , using machine learning algorithms and techniques . they have been used to identify specific kinds of variables of interest to their respective investigations . their successes notwithstanding , the alert rates that the lsst survey promises require us to look at the problem a little differently : * the alert broker needs to handle alert data volumes at the rate that lsst is capable of generating , i.e. thousands of alerts per minute . they need to be processed with a latency that does not make them stale : i.e. since lsst will produce alerts with a latency of @xmath5 minute , the broker must process those alerts without introducing significantly larger delays to the alert stream . * the alert broker needs to serve generic needs : i.e. its design should not be limited to identifying specific pre - defined kinds of celestial sources . * it should store and archive all alerts , and be able to append contextual information for any celestial sourc(es ) associated with that alert . it should be able to integrate results from any followup investigation of sources . achieving these goals requires the combined efforts of astronomers with experience in time - domain astronomy , as well as computer scientists who can impose the design and methods necessary to achieve the necessary end - to - end speed and scalability for dealing with lsst scale data rates and volumes . the knowledge we have about an alert , such as brightness , change in flux , galactic coordinates , ecliptic coordinates , distance to nearest galaxy , etc . , constitute features that can probabilistically characterize alerts . we re - iterate that this is a broad characterization , not a specific classification : the latter will have to come from software systems further downstream . because of the time - scale of lsst exposures , with a new image every @xmath137 seconds , alerts must be processed rapidly to keep up with the data stream . classification often requires more complex analysis and usually a more complete light curve @xcite . for the prototype , we have selected the challenging problem of identifying the rarest of time domain phenomena : those that are least like things we know . alerts that appear to come from more commonplace astronomical sources are diverted , but saved for further use . we will discuss later how antares is structured so that it can be modified and applied to identify other kinds of phenomena , and thus become a generic tool . identifying the ` rarest of the rare ' leads us through the problem space that makes adapting to other needs relatively straight - forward . figure [ fig : antares ] illustrates the main components of the antares architecture@xcite . the overall design principles are open source and open access . the software will be available for anyone to implement and our implementation will be community driven . the alert stream can be tapped at many points throughout the system . in figure [ fig : antares ] alerts enter the system from the top center . the first stages provide annotation that add contextual value to the alerts . source association is a critical step to incorporate relevant astronomical knowledge for each alert . catalogs of astronomical information , as well as the lsst source catalog will be the basis for this source association . examples include the 2mass all - sky data release@xcite , the chandra source catalog@xcite , the nrao vla sky survey@xcite , the sloan digital sky survey@xcite , the nasa extragalactic database@xcite , and gaia@xcite , among many others . these external catalogs are collated and initially ingested to produce the _ aggregated astroobject catalog _ , shown near the top - left of figure [ fig : antares ] . this catalog will be updated from time to time with periodic queries to the external catalogs , and with new ` astroobjects ' from the episodic data releases of the lsst survey . even the proximity to known sources can provide useful constraints . a new alert is also tested for association with past alerts ( from a database maintained by antares , and shown in the figure as _ locus - aggregated annotated alerts _ ) and additionally from any other available external alert data sources . the history of flux measurements , such as a light curve , will be valuable annotation . the _ locus - aggregated annotated alerts _ is meant to be an efficient database that can be updated regularly is an essential element of the system . this will be a valuable astronomical resource on its own . as mentioned before , the skyalert system provides a similar annotation . the problem for the future is the scale of alerts and the resulting necessity of this efficient database being integrated into the system for brokering alerts . a central notion in our procedure is that of _ alert characterization_. this is a discriminant activity which uses the features to determine what ` kind ' of alert we have . we distinguish this task from ` classication ' , in that characterization is necessarily uncertain and probabilistic , while classication is a more certain association with a known astrophysical type . examples of broad characterizations include known variable star , extragalactic source , active galaxy , or likely moving object . these require looking at all of the features , and as such is a holistic analysis , as contrasted with feature derivation , which can be performed independently for each added feature . for example , a small change in magnitude might imply a stellar variable , but if it has not been detected before , and it is near a galaxy , it may be a supernova , but caught when the brightness is changing slowly . for many alerts , there will only be a small number of features available for characterization , especially for an initial detection . if there are not enough features for discrimination by filtering , we can apply a probabilistic expectation of variability based on position on the sky and known distributions of variability @xcite . for a position , we can construct a variability probability density function and predict the likelihood of the alert as observed . with more data , more features become available and more complex filtering algorithms can be used . antares will then use multiple layers of filters to sort the alerts and find the rarest or most interesting among them ( the focus of the prototype project ) . the filtering will be based on feature vectors , either directly supplied by the alert and associated contextual information , or derived therefrom . these features are then compared against the features from known time - variable phenomena , using a variety of methods . alerts that are likely to come from ` common - place ' phenomena are diverted away from the main processing stream . each stage lets through fewer and progressively less commonly characterized alerts . these may then be re - characterized in feature vector space that is different or of higher dimension and filtered again . the filtering stages are meant to be ordered so that most efficient ( decisions on most alerts in the least time ) filters are staged first . more time consuming and in - depth probing is reserved for the later stages , where the alerts have already been winnowed to a smaller number . experimentation will show us the most efficacious and efficient feature combinations and algorithms . the training of filters and algorithms will be aided using machine based experimentation with amelie ( see below in section [ subsec : amelie ] ) , and is an integral part of the development of the antares system . the * diverted alerts are not discarded : * in each filtering stage they are diverted from the main filtering stream but are still accessible to other filtering systems , including , potentially , copies of the antares system itself that are tuned to other specific goals . thus an _ external alert broker _ ( shown in the bottom right of figure [ fig : antares ] ) can utilize the value added material from antares to filter according to alternative needs and priorities . custom filters can be applied , allowing users to isolate exactly which of the alerts is of interest to them and thus address many different goals . these community - derived filtering algorithms will be applied in a multi - step process , allowing for better management of computational resources . by characterizing the alerts , the number of dimensions of feature space can be reduced . more complex filters can be applied to the smaller number of alerts after initial filtering stages . an important design consideration throughout the architecture of antares is the structured provision of community input . while antares will provide the overarching design of the alert analysis , it is the role of the astrophysical community to provide the specific algorithms used at various places along the filtering process . the arizona machine - experimentation laboratory ( amelie ) , figure [ fig : amelie ] ) , provides a system for constructing and testing structural - causal models @xcite . this essentially automates the scientific process and allows us to run experiments to test relationships among features , including relationships that have not yet been apparent . it can observe the operation of antaresand make it more efficient . the goal for the prototype is to distinguish rare and unusual objects . once it is operational , the next stage is to expand the scope to allow users to find any type of alert of interest to them . we foresee that there will be many stages of the antares system itself , processing different data streams over different time scales . the overall alert ecosystem could accommodate multiple alert input streams and thus find a general way to serve the astronomical community s needs . we acknowledge the nsf inspire grant ( cise ast-1344204 , pi : snodgrass ) that supports this work . as acknowledges many conversations with kirk borne , which seeded much of the thinking from which this project was born . j. leaman , w. li , r. chornock , and a. v. filippenko , `` nearby supernova rates from the lick observatory supernova search - i. the methods and data base , '' _ monthly notices of the royal astronomical society _ * 412 * , pp . 14191440 , 2011 . a. j. drake , s. g. djorgovski , a. mahabal , e. beshore , s. larson , m. j. graham , r. williams , e. christensen , m. catelan , a. boattini , a. gibbs , r. hill , and r. kowalski , `` first results from the catalina real - time transient survey , '' _ astrophysical journal _ * 696 * , pp . 870884 , 2009 . n. kaiser , h. aussel , b. e. burke , h. boesgaard , k. chambers , m. r. chun , j. n. heasley , k .- w . hodapp , b. hunt , r. jedicke , d. jewitt , r. kudritzki , g. a. luppino , m. maberry , e. magnier , d. g. monet , p. m. onaka , a. j. pickles , p. h. h. rhoads , t. simon , a. szalay , i. szapudi , d. j. tholen , j. l. tonry , m. waterson , and j. wick , `` pan - starrs : a large synoptic survey telescope array , '' in _ survey and other telescope technologies and discoveries _ , j. a. tyson and s. wolff , eds . , spie _ * 4836 * , pp . 154164 , 2002 . n. m. law , s. r. kulkarni , r. g. dekany , e. o. ofek , r. m. quimby , p. e. nugent , j. surace , c. c. grillmair , j. s. bloom , m. m. kasliwal , l. bildsten , t. brown , s. b. cenko , d. ciardi , e. croner , s. g. djorgovski , j. van eyken , a. v. filippenko , d. b. fox , a. gal - yam , d. hale , n. hamam , g. helou , j. henning , d. a. howell , j. jacobsen , r. laher , s. mattingly , d. mckenna , a. pickles , d. poznanski , g. rahmer , a. rau , w. rosing , m. shara , r. smith , d. starr , m. sullivan , v. velur , r. walters , and j. zolkower , `` the palomar transient factory : system overview , performance , and first results , '' _ publications of the astronomical society of the pacific _ * 121 * , pp . 13951408 , 2009 . e. hadjiyska , d. rabinowitz , c. baltay , n. ellman , p. nugent , r. zinn , b. horowitz , r. mckinnon , and l. r. miller , `` la silla - quest variability survey in the southern hemisphere , '' in _ new horizons in time - domain astronomy _ , e. griffin , r. hanisch , and r. seaman , eds . , _ iau symposium _ * 285 * , pp . 324326 , 2012 . r. d. williams , s. g. djorgovski , a. j. drake , m. j. graham , and a. mahabal , `` skyalert : real - time astronomy for you and your robots , '' in _ astronomical data analysis software and systems xviii _ , d. a. bohlender , d. durand , and p. dowler , eds . , _ astronomical society of the pacific conference series _ * 411 * , p. 115 , 2009 . j. s. bloom , j. w. richards , p. e. nugent , r. m. quimby , m. m. kasliwal , d. l. starr , d. poznanski , e. o. ofek , s. b. cenko , n. r. butler , s. r. kulkarni , a. gal - yam , and n. law , `` automating discovery and classification of transients and variable stars in the synoptic survey era , '' _ pasp _ * 124 * , pp . 11751196 , 2012 . m. p. van haarlem , m. w. wise , a. w. gunst , g. heald , j. p. mckean , j. w. t. hessels , a. g. de bruyn , r. nijboer , j. swinbank , r. fallows , _ et al . _ , `` lofar : the low - frequency array , '' _ astronomy & astrophysics _ * 556 * , p. a2 , 2013 . w. b. atwood , a. a. abdo , m. ackermann , w. althouse , b. anderson , m. axelsson , l. baldini , j. ballet , d. l. band , g. barbiellini , _ et al . _ , `` the large area telescope on the fermi gamma - ray space telescope mission , '' _ astrophysical journal _ * 697 * , pp . 10711102 , 2009 . v. l. krabbendam and d. sweeney , `` the large synoptic survey telescope preliminary design overview , '' in _ ground - based and airborne telescopes iii _ , l. m. stepp , r. gilmozzi , and h. j. hall , eds . , _ proc . spie _ * 7733 * , 2010 . , p. a. abell , j. allison , s. f. anderson , j. r. andrew , j. r. p. angel , l. armus , d. arnett , s. j. asztalos , t. s. axelrod , _ et al . _ , `` lsst science book , version 2.0 , '' _ arxiv e - prints _ , 2009 . arxiv:0912.0201 . r. d. williams and r. seaman , `` voevent : information infrastructure for real - time astronomy , '' in _ astronomical data analysis software and systems xv _ , c. gabriel , c. arviset , d. ponz , and s. enrique , eds . , _ astronomical society of the pacific conference series _ * 351 * , p. 637 , 2006 . r. seaman , r. williams , a. allan , s. barthelmy , j. bloom , j. brewer , r. denny , m. fitzpatrick , m. graham , n. gray , f. hessman , s. marka , a. rots , t. vestrand , and p. wozniak , `` ivoa recommendation : sky event reporting metadata version 2.0 , '' _ arxiv e - prints _ , 2011 . arxiv:1110.0523 . t. grav , r. jedicke , l. denneau , s. chesley , m. j. holman , and t. b. spahr , `` the pan - starrs synthetic solar system model : a tool for testing and efficiency determination of the moving object processing system , '' _ pasp _ * 123 * , pp . 423447 , 2011 . j. w. richards , d. l. starr , n. r. butler , j. s. bloom , j. m. brewer , a. crellin - quick , j. higgins , r. kennedy , and m. rischard , `` on machine - learned classification of variable stars with sparse and noisy time - series data , '' _ apj _ * 733 * , p. 10 , 2011 . r. angeloni , r. contreras ramos , m. catelan , i. dkny , f. gran , j. alonso - garca , m. hempel , c. navarrete , h. andrews , a. aparicio , j. c. beamn , c. berger , j. borissova , c. contreras pea , a. cunial , r. de grijs , n. espinoza , s. eyheramendy , c. e. ferreira lopes , m. fiaschi , g. hajdu , j. han , k. g. heminiak , a. hempel , s. l. hidalgo , y. ita , y .- b . jeon , a. jordn , j. kwon , j. t. lee , e. l. martn , n. masetti , n. matsunaga , a. p. milone , d. minniti , l. morelli , f. murgas , t. nagayama , c. navarro , p. ochner , p. prez , k. pichara , a. rojas - arriagada , j. roquette , r. k. saito , a. siviero , j. sohn , h .- i . sung , m. tamura , r. tata , l. tomasella , b. townsend , and p. whitelock , `` the vvv templates project . towards an automated classification of vvv light - curves . i. building a database of stellar variability in the near - infrared , '' _ astronomy & astrophysics _ * in press * , 2014 . arxiv:1405.4517 . f. j. masci , d. i. hoffman , c. j. grillmair , and r. m. cutri , `` automated classification of periodic variable stars detected by the wide - field infrared survey explorer , '' _ astronomical journal _ * in press * , 2014 . arxiv:1402.0125 . t. matheson , a. saha , r. snodgrass , and j. kececioglu , `` antares : a prototype transient broker system , '' in _ american astronomical society meeting _ , _ american astronomical society meeting abstracts _ * 223 * , p. # 343.02 , 2014 . t. matheson , a. saha , r. snodgrass , and j. kececioglu , `` antares : the arizona - noao temporal analysis and response to events system , '' in _ hot - wiring the transient universe 3 _ , p. wozniak , m. graham , and a. mahabal , eds . , 2014 . m. f. skrutskie , r. m. cutri , r. stiening , m. d. weinberg , s. schneider , j. m. carpenter , c. beichman , r. capps , t. chester , j. elias , j. huchra , j. liebert , c. lonsdale , d. g. monet , s. price , p. seitzer , t. jarrett , j. d. kirkpatrick , j. e. gizis , e. howard , t. evans , j. fowler , l. fullmer , r. hurt , r. light , e. l. kopan , k. a. marsh , h. l. mccallon , r. tam , s. van dyk , and s. wheelock , `` the two micron all sky survey ( 2mass ) , '' _ astronomical journal _ * 131 * , pp . 11631183 , 2006 . i. n. evans , f. a. primini , k. j. glotfelty , c. s. anderson , n. r. bonaventura , j. c. chen , j. e. davis , s. m. doe , j. d. evans , g. fabbiano , e. c. galle , d. g. gibbs , ii , j. d. grier , r. m. hain , d. m. hall , p. n. harbo , x. ( helen he , j. c. houck , m. karovska , v. l. kashyap , j. lauer , m. l. mccollough , j. c. mcdowell , j. b. miller , a. w. mitschang , d. l. morgan , a. e. mossman , j. s. nichols , m. a. nowak , d. a. plummer , b. l. refsdal , a. h. rots , a. siemiginowska , b. a. sundheim , m. s. tibbetts , d. w. van stone , s. l. winkelman , and p. zografou , `` the chandra source catalog , '' _ astrophysical journal supplement _ * 189 * , pp . 3782 , 2010 . k. n. abazajian , j. k. adelman - mccarthy , m. a. ageros , s. s. allam , c. allende prieto , d. an , k. s. j. anderson , s. f. anderson , j. annis , n. a. bahcall , _ et al . _ , `` the seventh data release of the sloan digital sky survey , '' _ astrophysical journal supplement _ * 182 * , pp . 543558 , 2009 . g. helou , b. f. madore , m. schmitz , m. d. bicay , x. wu , and j. bennett , `` the nasa / ipac extragalactic database . , '' in _ databases and on - line data in astronomy _ , m. a. albrecht and d. egret , eds . , _ astrophysics and space science library _ * 171 * , pp . 89106 , 1991 .
the arizona - noao temporal analysis and response to events system ( antares ) is a joint project of the national optical astronomy observatory and the department of computer science at the university of arizona . the goal is to build the software infrastructure necessary to process and filter alerts produced by time - domain surveys , with the ultimate source of such alerts being the large synoptic survey telescope ( lsst ) . the antares broker will add value to alerts by annotating them with information from external sources such as previous surveys from across the electromagnetic spectrum . in addition , the temporal history of annotated alerts will provide further annotation for analysis . these alerts will go through a cascade of filters to select interesting candidates . for the prototype , ` interesting ' is defined as the rarest or most unusual alert , but future systems will accommodate multiple filtering goals . the system is designed to be flexible , allowing users to access the stream at multiple points throughout the process , and to insert custom filters where necessary . we describe the basic architecture of antares and the principles that will guide development and implementation .
the coexistence of magnetism and superconductivity in heavy fermion compounds is one of the central issues in condensed matter physics@xcite . in particular , urhge and ucoge have attracted much attention in recent years because they show the coexistence of long - range ferromagnetic order and superconductivity under an ambient pressure@xcite . they are weak ferromagnets , with @xmath3 k and @xmath4 @xmath5 ( urhge ) , and @xmath6 k and @xmath7 @xmath5 ( ucoge ) . they undergo transition into superconducting states below @xmath8 k ( urhge ) @xcite and @xmath9 k ( ucoge ) @xcite , and the superconducting state and magnetic orderings coexist below @xmath10 . the natures of the superconductivity and magnetism in these compounds have been well studied experimentally . for example , the magnetic field and the pressure phase diagrams of these compounds have been obtained experimentally , and it has been suggested that these compounds are located near the quantum critical point of the magnetic transition@xcite . furthermore , the nqr study of ucoge clarified that the superconducting state and long - range magnetic ordering uniformly coexist in this compound @xcite . on the other hand , the electronic structures of these compounds are not well understood . an itinerant nature of u 5@xmath1 states has been expected from the small ordering moments in the ferromagnetic phase as well as their pressure dependences @xcite . in addition , x - ray photoelectron spectroscopy studies of urhge @xcite , urh@xmath11ru@xmath12ge @xcite , and ucoge @xcite showed that the u 5@xmath1 state forms peak structures near the fermi level ( @xmath13 ) , suggesting that the u 5@xmath1 electrons in these compounds have an itinerant nature . however , precise information about u 5@xmath1 states has not been obtained in these studies , and a definitive conclusion has not yet been obtained . to establish realistic models of superconductivity and magnetism in these compounds , it is essential to reveal their microscopic electronic structures . here we report the direct observation of the band structure of urhge through an angle - resolved photoelectron spectroscopy ( arpes ) study . the band structure of urhge is obtained for the first time , and it is found that the u 5@xmath1 electrons form fermi surfaces ( fs s ) in this compound . photoemission experiments were performed at the soft x - ray beamline bl23su of spring-8 @xcite . the overall energy resolution in angle - integrated photoemission ( aipes ) experiments at @xmath14=800 ev was about 110 mev , and that in arpes experiments at @xmath15 ev was 100160 mev , depending on the photon energies . the position of @xmath13 was carefully determined by measurements of the evaporated gold film . clean sample surfaces were obtained by cleaving the sample _ in situ _ with the surface parallel to the @xmath16 plane . the position of arpes cuts was calculated by assuming a free - electron final state with an inner potential of @xmath17=12 ev . = 800 ev . ( a ) valence - band spectra of urhge and calculated partial density of states of the rh 4@xmath18 and u 5@xmath1 states . ( b ) u 4@xmath1 core - level spectrum of urhge together with those of the typical itinerant compound ub@xmath19 and localized compound upd@xmath20 . ] first , we present the aipes spectra of urhge . figure [ aipes ] ( a ) shows the valence - band spectrum of urhge taken at @xmath14=800 ev . the sample temperature was kept at 20 k , and the compound is in a paramagnetic phase . the spectrum is identical to that in ref . @xcite . in this photon energy range , the contributions from u 5@xmath1 and rh 4@xmath18 states are dominant , and those from @xmath21 and @xmath22 states are two or three orders of magnitude smaller than those of u 5@xmath1 and rh 4@xmath18 states @xcite . in the valence - band spectrum , there is a sharp peak structure just below @xmath13 . on the high - binding - energy side , there is a broad peak structure distributed at @xmath23 ev . to understand the origin of this peak structure , we have compared this spectrum with the result of the band - structure calculation . in the calculation , relativistic - linear - augmented - plane - wave ( rlapw ) band - structure calculations@xcite within the local density approximation ( lda)@xcite were performed for urhge treating all u 5@xmath1 electrons as being itinerant . in the lower part of the fig . @xcite ( a ) , the calculated u 5@xmath1 and rh 4@xmath18 density of states broadened by the instrumental resolution are indicated . comparison between the spectrum and the calculated density of states suggests that the sharp peak structure near @xmath13 and the broad peak structure on the high - binding - energy sides correspond to u 5@xmath1 and rh 4@xmath18 states , respectively . here , it should be noted that a shoulder - like structure is recognized at around @xmath24 ev in the experimental spectrum . a similar structure is present in the calculated u 5@xmath1 dos as well , and this suggests that this shoulder structure originates not from the electron correlation effect , but from the band structure . the overall spectral shape is consistent with the results of the band - structure calculation . figure [ aipes ] ( b ) shows the u 4@xmath1 core - level spectrum of urhge together with those of the typical itinerant 5@xmath1 compound ub@xmath19 and localized 5@xmath1 compound upd@xmath20 . these data are taken from ref.@xcite . they show a spin - orbit splitting corresponding to u 4@xmath25 and u 4@xmath26 , and both of them have asymmetric line shapes . the core - level spectrum of urhge has a relatively simple spectral line shape . it is similar to that of the itinerant 5@xmath1 compound ub@xmath19 , suggesting that u 5@xmath1 electrons in urhge have an itinerant character . meanwhile , the spectrum of urhge is much broader than that of ub@xmath19 , and is accompanied by a satellite structure on the high - binding - energy side , as has been observed in the upd@xmath20 spectrum . this implies that the u 5@xmath1 electrons in urhge have a correlated character as well . we first explain about the brillouin zone and the calculated fss of urhge . figure [ 3dfs ] shows the simple orthorhombic brillouin zone of urhge and the calculated fss in the paramagnetic phase . in the band - structure calculation , bands 6972 form fss as shown in the figure . fs 69 is a small hole pocket around the y point . fs 70 has a highly three - dimensional shape . it forms a connected hole fs along the @xmath27 direction and a hole pocket fs in the middle of the @xmath28 and x points . fs 71 is an electron fs with a grid - like shape spreading along the @xmath29@xmath30 plane . fs 72 has a pillar - like shape along the @xmath30 direction at the corner of the brillouin zone . all these calculated fss have large contributions from u 5@xmath1 states . the calculation suggests that the electronic structure of this compound is highly three - dimensional in nature . figure [ arpes1 ] shows the arpes spectra of urhge measured along the x-@xmath28-x [ fig . [ arpes1](a ) ] , u - z - u [ fig . [ arpes1](b ) ] , and s - y - s [ fig . [ arpes1](c ) ] high - symmetry lines . the sample temperature was kept at 20 k , which was in the paramagnetic phase . the position of the arpes cut in the momentum space is calculated based on the free electron final sates , and the photon energies used were @xmath31=625 ev for the x-@xmath28-x and u - z - u lines , and @xmath31=700 ev for the s - y - s line . in these arpes spectra , clear energy dispersions were observed . in the vicinity of @xmath13 , there exist dispersive bands with strong intensities . these are contributions from the u 5@xmath1 quasiparticle bands . the peak intensities of these structures have strong momentum dependences , suggesting that the u 5@xmath1 quasiparticle bands have finite energy dispersions . on the high - binding - energy side ( @xmath32 ev ) , there exist dispersive bands with strong intensities . these are the contributions from the rh 4@xmath18 bands . here , it should be noted that those bands are not symmetric relative to the high - symmetry points . for example , the spectra measured along the x-@xmath28-x high - symmetry line are not symmetric relative to the x point in fig . [ arpes1 ] ( a ) . this may be due to the photoemission structure factor effect as has been observed in arpes spectra of other materials @xcite . to eliminate this effect , we have symmetrized these arpes spectra relative to the high - symmetry points . figures [ arpes2 ] ( a)-[arpes2](c ) show the symmetrized arpes intensity maps . the behaviors of the bands are clearly demonstrated in these images . to evaluate the validity of the itinerant description of the u 5@xmath1 states in this compound , we compare the present arpes spectra with the result of the band - structure calculation treating all u 5@xmath1 electrons as being itinerant . figures [ arpes2 ] ( d)-[arpes2 ] ( f ) show the calculated band structure . the color coding is the projection of the contributions from u 5@xmath1 states and rh 4@xmath18 states respectively . the contributions from u 5@xmath1 states are distributed in the energy range of @xmath33 ev , while those from rh 4@xmath18 states are mainly distributed in the energy range of @xmath34 ev . many dispersive bands exist in the calculation , and it is difficult to compare them with the experimentally observed bands one by one . meanwhile , the overall band structures have some similarities between the experiment and the calculation . on the high - binding - energy side ( @xmath35 ev ) , the contributions from rh 4@xmath18 states were observed in both the experiment and the calculation . in the vicinity of @xmath13 , there are weakly dispersive bands in both the experiment and the calculation , and these are contributions from u 5@xmath1 states . there exist few bands in the energy region in between them ( @xmath36 ev ) , and some calculated bands seem to correspond to the experimental spectra . for example , there is an inverted parabolic band centered at the y point in the energy region of @xmath37 ev in the calculation [ fig . [ arpes2 ] ( f ) ] that exists in the experiment [ fig . [ arpes2 ] ( c ) ] . the similar inverted parabolic bands centered at the @xmath28 point in the energy region of @xmath38 ev ( fig . [ arpes2 ] ( d ) ) are seen in the experimental spectra [ fig . [ arpes2](a ) ] . to see details of the band structure near @xmath13 as well as its correspondence to the band - structure calculation , a blowup of the experimental arpes spectra and their simulation based on band - structure calculation are shown in fig . [ arpes3 ] . figure [ arpes3 ] shows a comparison between experimental arpes spectra and their simulations along the x-@xmath28-x [ fig . [ arpes3 ] ( a ) ] , u - z - u [ fig . [ arpes3 ] ( b ) ] , and s - y - s high - symmetry lines [ fig . [ arpes3 ] ( b ) ] . these spectra are divided by the fermi - dirac function broadened by the instrumental energy resolution to observe the states near @xmath13 more clearly . the approximate positions of experimental bands are estimated by the second derivatives of the energy distribution curves or momentum distribution curves , and are shown by dashed lines along the u - z - u high - symmetry line [ fig . [ arpes3 ] ( b ) ] and the s - y - s high - symmetry lines [ fig . [ arpes3 ] ( c ) ] . in the simulation , the following effects were taken into account : ( i ) the broadening along the @xmath30 direction due to the finite escape depth of photoelectrons , ( ii ) the lifetime broadening of the photo - hole , ( iii ) the photoemission cross sections of orbitals , and ( iv ) the energy resolution and the angular resolution of the electron analyzer . the details are described in ref . @xcite . the correspondence between the arpes spectra and the calculations is more clearly recognized . a detailed comparison suggests that there are some similarities between the experiment and the calculation . some agreements are clearly identified , especially in the spectra along the u - z - u and s - y - s high - symmetry lines . for example , along the u - z - u high - symmetry line , the experimentally observed three bands b , c , and d , correspond to the calculated bands 6566 , 6768 , and 6970 , respectively . in addition , there are similar qualitative agreements in the spectra along the s - y - s high - symmetry line . bands a , b , c , d , and e in the experimental spectra correspond to the bands 6364 , 6566 , 6768 , 69 - 70 , and 7172 , respectively . in particular , band e forms a small electron pocket around the s point , which can be clearly recognized in the spectra normalized by the areas of the momentum distribution curves shown in the inset in the fig . [ arpes3 ] ( c ) . a similar electron pocket exists in the band - structure calculation as bands 71 and 72 . on the other hand , band d does not have a large energy dispersion , and it does not form a fs as bands 69 and 70 do in the calculation . therefore , the agreement is unsatisfactory , especially in bands near @xmath13 . the agreement is further unclear in the spectra along the x-@xmath28-x high - symmetry line . the calculated spectra have a complicated structure , and it seems very different from the experimental spectra . however , there are still some corresponding features in both the experiment and the calculation . for example , the inverted parabolic band with its apex at @xmath39 0.2 ev at the x point in the experimental spectra has a correspondence to bands 6364 in the calculation . the inverted parabolic band with its apex at @xmath39 1.0 ev at the @xmath28 point corresponds to part of the calculated bands 6165 . the states near @xmath13 in the experimental spectra are rather featureless , and they are very different from the calculation . therefore , the agreement between the experiment and the calculation is limited , especially in states near @xmath13 , and we could not obtain information on the shape of fs s from the present experimental data . in addition , many flat bands are expected around @xmath13 in the calculation , and even a tiny change in @xmath13 , by the order of 10 mev , drastically changes the shape of calculated fs s . this makes it more difficult to compare states near @xmath13 between the experiment and the calculation . next , we show the changes in the electronic structure due to the ferromagnetic transition . figures [ tempdep ] ( a ) and [ tempdep ] ( b ) show blowups of arpes spectra measured along the x-@xmath28-x line at 20 k ( paramagnetic phase ) and 6 k ( ferromagnetic phase ) , respectively . although the changes are not significant , some temperature dependencies were clearly observed . here , it should be noted that the energy difference between these two sample temperatures ( 20 k , @xmath401.7 mev ; 6 k , @xmath400.5 mev ) is much smaller than the energy scale of the changes in the arpes spectra , suggesting that the changes are not due to a thermal broadening effect . to see details of the changes , we have subtracted the spectra measured at 20 k from those measured at 6 k. the intensity map of the difference in the spectra measured at 20 k vs 6 k is shown in fig . [ tempdep ] ( c ) , and the spectra at the @xmath28 point are depicted in fig . [ tempdep ] ( d ) . intensities are normalized with the highest intensity in the momentum and energy area shown in this figure . both spectra are normalized to the intensities of the rh 4@xmath18 bands located at @xmath41 ev . there are two kinds of changes in the spectral functions . first , the intensities in the region of @xmath42 ev , which correspond to contributions mainly from u 5@xmath1 quasiparticle bands , decrease in the ferromagnetic phase . the area is designated a in the figure . the changes in spectral intensities near @xmath13 suggest that the ferromagnetic ordering in this compound originates from the itinerant u 5@xmath1 quasiparticle bands . in addition to these changes , the intensities at around @xmath43 ev at the @xmath28 point decrease . the area is designated b in the figure . the origin of this change is discussed in the next section . accordingly , we have observed dispersive u 5@xmath1 quasiparticle bands near @xmath13 in arpes spectra of urhge . they form fss in this compound , suggesting that they have basically an itinerant nature . on the other hand , the agreement between the experimentally obtained spectra and the band - structure calculation is limited . the agreement is not satisfactory as those of the itinerant paramagnets ufega@xmath44 @xcite and ub@xmath19 @xcite , or the itinerant antiferromagnet un @xcite . in particular , the states near @xmath13 ( @xmath2 ev ) show considerable deviations from the calculation . the ellipsoidal pocket fs with a size of about 7 % of the brillouin zone was observed in sdh oscillations @xcite , but it does not exist in the calculated fs s . this also suggests that the shape of fs s might be different from the calculation . these claim that the lda might be a reasonable starting point to describe its electronic structure , but inclusion of the electron correlation is needed to describe its electronic structure . furthermore , the core - level spectrum of urhge has a satellite peak on the high - binding - energy side of the main line as shown in fig . [ aipes ] ( b ) , suggesting the importance of the dynamical screening effect in urhge . it has been shown that the inclusion of dynamical correlation effects alters the band structure near @xmath13 @xcite , and such a theoretical framework is a step forward to the understanding of this compound . changes in the spectral line shape due to the ferromagnetic transition were observed in the vicinity of @xmath13 as well as on the high - binding - energy side ( @xmath45 ev ) . the former change suggests that the ferromagnetic ordering in this compound is due to the changes in itinerant quasiparticle bands near @xmath13 . although their details were not resolved in the present spectra , the changes are presumably due to the splitting of bands into majority - spin and minority - spin bands in the ferromagnetic phase as has been observed in ute @xcite and uir @xcite since u 5@xmath1 electrons have an itinerant nature in urhge as well . in the stoner - type mean - field model of itinerant ferromagnetism , the exchange splitting energy @xmath46 is expressed as @xmath47 where @xmath48 and @xmath49 represent the stoner parameter and the magnetization respectively . the stoner parameter @xmath48 might be somewhat different in the cases of ute and urhge , but the smaller magnetic moment of urhge ( @xmath4 @xmath5 ) compared to ute ( @xmath50 @xmath5 ) implies that the energy shift of the majority and minority bands ( @xmath51 ) of urhge should be much smaller than that of ute ( @xmath52 50 mev@xcite ) . furthermore , it is experimentally known that @xmath46 approximately scales with @xmath53 in itinerant ferromagnets@xcite , and the one order - lower transition temperature of urhge ( @xmath3 k ) compared to ute ( @xmath54 k ) also argues that its @xmath46 should be much smaller than that of uir . these imply that the @xmath55 of urhge should be of the order of 10 mev , and its direct observation is difficult at the present energy resolution ( @xmath56 mev ) . meanwhile , the latter change on the high - binding - energy side is not the mean - field - like splitting of energy bands , but the change in peak structure . this change might originate from the incoherent part of the spectrum due to the correlation effect of u 5@xmath1 states . riseborough @xcite suggested that the incoherent spin excitation produces an incoherent peak in the off-@xmath13 region in a weak ferromagnet near a quantum critical point . a similar change was observed in the spectra of the ferromagnet uir , where the peak at the @xmath57 point and @xmath580.5 ev was changed , in addition to the state near @xmath13 @xcite , by the ferromagnetic transition . therefore , this change on the high - binding - energy side might be a common feature of uranium ferromagnets located near a quantum critical point . in conclusion , we have found that quasiparticle bands with large contributions from u 5@xmath1 states form fss of urhge . the overall band structure of urhge is explained by the band - structure calculation based on the lda , but the shape of the band structure near @xmath13 shows considerable deviations from the calculation . the experimental band structure near @xmath13 is rather featureless , and the shapes of fs s are qualitatively different from the calculation . in addition , the u 4@xmath1 core - level spectrum of urhge is accompanied by a satellite peak , which is a signature of the electron correlation effect . these results suggest that the inclusion of an electron correlation effect is essential to describe its electronic structure although the band - structure calculation is an appropriate starting point . the changes in arpes spectra associated with the ferromagnetic transition were observed in the band near @xmath13 as well as states on the high - binding - energy side . the former should be due to the exchange splitting of quasiparticle bands , while the latter might be related to the correlated nature of u 5@xmath1 states . we would like to thank p. riseborough for stimulating discussion and comments . the experiment was performed under proposal no . 2010b3824 at spring-8 bl23su . the present work was financially supported by a grant - in - aid for scientific research from the ministry of education , culture , sports , science , and technology , japan , under contact no . 21740271 ; grants - in - aid for scientific research on innovative areas `` heavy electrons '' ( nos . 20102002 and 20102003 ) from the ministry of education , culture , sports , science , and technology , japan ; and the shorei kenkyu from hyogo science and technology association . s. fujimori , t. ohkochi , i. kawasaki , a. yasui , y. takeda , t. okane , y. saitoh , a. fujimori , h. yamagami , y. haga , e. yamamoto , y. tokiwa , s. ikeda , t. sugai , h. ohkuni , n. kimura and y. nuki , j. phys . * 81 * , 014703 ( 2012 ) . a. yokoya , t. sekiguchi , y. saitoh , t. okane , t. nakatani , t. shimada , h. kobayashi , m. takao , y. teraoka , y. hayashi , s. sasaki , y. miyahara , t. harami and t.a . sasaki , j. synchrotron rad . * 5 * , 10 ( 1998 ) . t. durakiewicz , c. d. batista , j. d. thompson , c. g. olson , j.j . joyce , g. h. lander , j. e. gubernatis , e. guziewicz , m. t. butterfield , a. j. arko , j. bona , k. matternberger , and o. vogt , phys . lett . * 93 * , 267205 ( 2004 ) . h. yamagami , t. ohkochi , s. fujimori , t toshimitsu , a. yasui , t. okane , y saitoh , a. fujimori , y. haga , e. yamamoto , s. ikeda and y. onuki , j. phys . : conference series * 200 * , 012229 ( 2010 ) .
the electronic structure of the ferromagnetic superconductor urhge in the paramagnetic phase has been studied by angle - resolved photoelectron spectroscopy using soft x rays ( @xmath0=595 - 700 ev ) . dispersive bands with large contributions from u 5@xmath1 states were observed in the arpes spectra , and form fermi surfaces . the band structure in the paramagnetic phase is partly explained by the band - structure calculation treating all u 5@xmath1 electrons as being itinerant , suggesting that an itinerant description of u 5@xmath1 states is a good starting point for this compound . on the other hand , there are qualitative disagreements especially in the band structure near the fermi level ( @xmath2 ev ) . the experimentally observed bands are less dispersive than the calculation , and the shape of the fermi surface is different from the calculation . the changes in spectral functions due to the ferromagnetic transition were observed in bands near the fermi level , suggesting that the ferromagnetism in this compound has an itinerant origin .
intensity mapping of the cumulative co and other millimeter and submillimeter line emission from early galaxies has been proposed as a new means to probe very large - scale structures in the distant universe ( carilli 2011 ; gong et al . 2011 ; gong et al . 2012 ; yue et al . intensity mapping entails low spatial and spectral resolution imaging of the sky to obtain the mean brightness due to the cumulative emission from myriad discrete cosmic sources . while interferometric arrays like alma , the jvla , and noema , can detect co and [ cii ] 158@xmath0 m ( and in cases of high luminosity sources , other lines ) , from individual galaxies at high redshift , the fields of view are very small , and the integration times are long . these telescopes are inadequate for measuring the galaxy distribution on the very large scales relevant to cosmological questions , such as the baryon acoustic oscillations at intermediate redshifts , or the large - scale distribution of galaxies that reionize the universe . the latter is of particular interest for cross correlation studies with very wide field , low - resolution hi 21 cm images of the intergalactic medium during cosmic reionization ( lidz et al . 2011 ) . the integrated millimeter and submillimieter line emission from early galaxies has also been recognized as a possible significant contaminant of measurements of the spectral and spatial fluctuations of the cosmic microwave background ( cmb ; righi et al . 2008a , b ; chluba & sunyaev , 2012 ; de zotti et al . 2015 ; mashian et al . 2016 ) . for example , modeling suggests ( mashian et al . 2016 ) that the integrated co line emission could be significantly higher than the primordial spectral distortions due to other cosmological effects ( e.g. , chluba & sunyaev , 2012 ; sunyaev & khatri , 2013 ; tashiro 2014 ) , and may be measurable with next generation instruments like the primordial inflation explorer ( pixie ; kogut et al . 2014 ) . numerous calculations have been done to predict the mean sky brightness due to emission lines from co at intermediate and high redshift , and [ cii ] 158@xmath0 m emission at very high redshift ( see section 2 ) . these predictions are based on either empirical estimates using proxies for the line emission , such as the cosmic star formation rate density , or large scale cosmological simulations of galaxy formation , with recipes to relate proxy measurements or simulated properties to line luminosities . in this paper , we present direct measurements of the summed line luminosity from individual sources in bands around 99 ghz and 242 ghz . these measurements are based on the aspecs program , corresponding to a broad band spectral line deep field of the udf at 1.25 mm and 3 mm ( decarli et al . 2016 ; aravena et al . 2016a ; walter et al . 2016 ) . from these measurement , we derive the mean brightness temperature at a given observing frequency due to high redshift galaxies . as a pilot study with alma , the fields are necessarily small , and the number of galaxies few . however , the measured quantity is direct : line emission from early galaxies . hence , no modeling or conversion factors are required . the dominant contribution to the integrated line brightness from high redshift galaxies in the 99ghz band is due to rotational transitions of co from galaxies at intermediate to high redshift . other molecular tracers , such as the high dipole moment molecules like hcn and hco@xmath4 , are typically 10 times , or more , fainter than co , while the atomic fine structure lines would be from galaxies at improbable redshifts ( @xmath5 ; see carilli & walter 2013 ) . at 242ghz , the integrated line brightness will be some combination of higher order co lines from intermediate and high redshift galaxies , plus a possible contribution from [ cii ] 158@xmath0 m line emission from galaxies at @xmath1 to 7 , and other fine structure lines at lower redshift . we consider each in turn . considering co in the 99ghz band , predictions of the mean co sky brightness from early galaxies have taken two approaches . first is an empirical use of the measured evolution of the cosmic star formation rate density , and/or the cosmic fir background , converted to co luminosity by adopting a co - to - fir or star formation rate conversion factor ( lidz et al . 2011 ; righi et al . 2008 ; de zotti et al . a related calculation is to consider the star formation rate density required to reionize the neutral intergalactic medium at high redshift , subsequently converted to co luminosity using said conversion factors ( carilli et al . 2011 ; gong et al . while based on celestial measurements , these methods involve significant uncertainties inherent in both the determination of the cosmic star formation rate density , and more importantly , the assumed star formation law relating co luminosity to fir luminosity , or to star formation rate ( kennicutt & evans 2012 ; carilli & walter 2013 ) . the latter may entail a dual conversion of star formation rate to total gas mass , then total gas mass to co luminosity . there is the additional uncertainty in the assumed gas excitation when modeling the contribution to the mean brightess at a given observing frequency from different co transitions from galaxies at different redshifts . the second method for predicting the mean co sky brightness is through cosmological numerical simulations ( mashian et al . 2016 ; gong et al . 2011 ; li et al . such simulations can be normalized to eg . an observed galaxy luminosity function at a given redshift , although ultimately , even the most detailed simulations rely on recipes to convert from simulated to observable quantities . this is particularly difficult in the case of tracer molecules , such as co , while also including their excitation state . in summary , the predictions at around 100ghz for the mean brightness from co lines from intermediate and high redshift galaxies range from 1.5@xmath0k ( righi et al . 2008 ) to about 10@xmath0k ( marshian & loeb 2016 ) . two recent observations have set upper limits to the co brightness from distant galaxies using co intensity mapping . the first entailed a cross correlation of wmap images with maps of very large - scale structures from the sdss , namely the photometric quasar sample and the luminous red galaxy sample ( pullen et al . the cross correlation technique removes numerous systematic errors . pullen et al . estimate upper limits to the mean brightness temperature of co 1 - 0 or 2 - 1 of about @xmath6k in the 30 ghz to 90 ghz range . the second was an interferometric measurement of the brightness fluctuations at 30ghz using the sunyaev - zeldovich array ( keating et al . keating et al . quote an upper limit to the co 1 - 0 mean brightness of @xmath7k from @xmath8 galaxies . since both these measurements rely on modeling of the spatial structure in the signal , they depend on the assumed under - lying structural parameters . considering the 242ghz band , predictions also vary considerably . the most detailed modeling to date , including analysis of lines from co , [ cii ] , and [ ci ] , is presented in yue et al . ( 2015 ) . they use large scale cosmological simulations , plus physically motivated conversion factors ( vallini et al . 2015 ; pallottini et al . 2015 ) , to derive the line luminosities from early galaxies . they predict a [ cii ] 158@xmath0 m brightness of @xmath9k around 242ghz from @xmath10 galaxies . at this frequency , they obtain a similar contribution from the [ ci ] lines at rest frame frequencies of 492ghz and 809ghz , from lower redshift galaxies . the dominant line contribution to the mean brightness at 242ghz in their models comes from co emission from galaxies at intermediate to high redshift , for which they derive a mean brightness of @xmath11k . note that , in their models , the [ cii ] contribution increases rapidly with increasing observing frequency , to @xmath12k at 316ghz ( comparable to co ) , due to galaxies at @xmath13 . conversely , gong et al . ( 2012 ) perform an analytic calculation of the expected [ cii ] surface brightness based on ism physics and halo statistics , and predict a substantially larger contribution of [ cii ] at 242 ghz of @xmath14k . the alma spectral deep field observations ( aspecs ) and results are described in walter et al . ( 2016 ) ; aravena et al . ( 2016a ) ; decarli et al . ( 2016 ) . in brief , we surveyed a @xmath15 arcmin@xmath16 field in the udf to a 3-@xmath17 depth of @xmath18 jy km s@xmath19 ( assuming line widths of 200 km s@xmath19 ) over the frequency range 84115 ghz ( 3 mm ) , and of @xmath20 jy km s@xmath19 over the frequency range 212272 ghz . in the analysis below , we adopt the mean frequencies for each band , which are 99ghz and 242ghz . the observations are sensitive to galaxies over a wide range in redshift , depending on co transition . the typical co luminosity limits are @xmath21 k km s@xmath19 pc@xmath16 at 3 mm and @xmath22 k km s@xmath19 pc@xmath16 at 1 mm at @xmath23 . the implied gas mass limits will depend on which co transition is being considered , at which redshift , and depend critically on assumed co excitation , in particular for the high order transitions , since the total gas mass is derived by extrapolation to low order . for reference , at the typical redshifts and transitions of the detected galaxies , these limits imply galaxies with gas masses of 3 to 10@xmath24 m@xmath25 , for a galactic conversion factor of co 1 - 0 luminosity to total molecular gas mass . we discuss this point further in section 4.1 . for [ cii ] at very high redshift ( @xmath10 ) , our observations are sensitive to galaxies with star formation rates @xmath26 m@xmath25 year@xmath19 , using the de looze et al . ( 2011 ) conversion . line emitting galaxies were identified using multiple three dimensional search algorithms , and a series of tests were made for completeness and fidelity ( walter et al.2016 ) . once a line candidate was identified , a search was made for an optical or near - ir counterpart . decarli et al . ( 2016a ) discuss how a given line is identified as a specific co transition . in some cases , the detection ( or the lack of detection ) of multiple co transitions over the broad frequency range constrains the redshift determination . if an optical / nir counterpart is present , literature information on the redshift of the source ( via spectroscopy or sed fitting of the photometry ) was also used . the lack of an optical counterpart is used to rule out low redshift interpretations in some cases . ultimately , for some sources there can be ambiguity as to the transition in question , and therefore the redshift . this is dealt with via a bootstrapping approach ( see decarli et al . however , in the context of the analysis below , this is not an issue , since we simply sum all the lines detected in the blind survey in a give observing band , independent of what transition and redshift the line happens to be . for completeness , figure 1 shows a compilation of all the candidate line detections in the survey , as presented in walter et al . there are a total of 21 candidate lines above 5@xmath17 . in 6 cases , line identifications are unequivocally confirmed , through detection of other co transitions , and/or an optical galaxy with a spectroscopic redshift . for the rest of the lines , extensive quantitative tests are made , and we only include lines with a @xmath27 fidelity rating . see decarli et al . ( 2016a ) for more details on the statistical analysis , and walter et al . ( 2016 ) for total intensity co images , and optical images , of all the candidates . at this fidelilty level , we expect to have roughly as many spurious detections as sources missing from the survey due to noise fluctuations ( decarli et al . 2016a ) . line candidates from aspecs blind survey ( walter et al . the red regions show the spectral region over which the signal - to - noise was calculated ( see decarli et al . the mean line brightness temperatures are calculated using an empirical approach of summing the lines detected in the blind survey . the process is simple : table 2 in walter et al . ( 2016 ) lists the lines detected according to the blind search criteria outlined in section 3 . we sum the total flux from all the lines detected in a given band , in jy km s@xmath19 , which is equivalent dimensionally to jy hz or ergs s@xmath19 @xmath28 . we then divide by the total band width covered in the blind survey , which results in a mean flux density over the full band and over the full field , @xmath29 , in jy . the mean brightness temperature at the observed wavelength , @xmath30 , is then derived using the angular area of the field employed in the blind search , @xmath31 , under the rayleigh - jeans appoximation : @xmath32 , where @xmath30 is in centimeters and @xmath31 is in arcseconds@xmath16 . for the 99ghz band , the total flux for the 10 lines detected in the band is @xmath33 jy km s@xmath34 jy hz . the total bandwidth is 31ghz , so the mean flux density across the band is : @xmath35 jy . the field covered by the survey was 3600 arcsecond@xmath16 . hence , the mean brightness temperature , @xmath2k . for the 242ghz band , the total flux for the 11 lines detected in the band is @xmath36 jy km s@xmath37 jy hz . the total bandwidth is 60ghz , so the mean flux density across the band is : @xmath38 jy . the field covered by the survey was also 3600 arcsecond@xmath16 . hence , the mean brightness temperature , @xmath3k . as a pilot alma study , we reemphasize that the volumes in question are small , as are the number of detections . hence , our conclusions and uncertainties are dominated by cosmic variance and simple shot noise ( poisson statistics ) . aravena et al . ( 2016b ) consider the issue of cosmic variance in the context of our particular field . based on the drop - out galaxy counts , and the bright submm source counts , this bias might be as large as a factor two ( low ) . on the other hand , consideration of the contribution of faint submm continuum sources to the cosmic infrared background , based on our deeper aspecs alma data , suggests a factor closer to unity ( aravena et al . regardless , since this is a direct survey of the observable in question , namely , mean brightness due to line emission from distant galaxies at a given observing frequency , the results remain of interest in general progress toward millimeter line intensity mapping , and a factor two uncertainty is inconsequential for our analysis in section 4.2 . our measurements are also lower limits , since we only sum lines detected . we do not extrapolate to , e.g. , lower or higher luminosity galaxies using an assumed luminosity function . considering co ( the dominant contributor at 99ghz , certainly , and likely at 242 as well ) , our detection threshold was set in order to reach what may be the knee in the co luminosity function at the primary redshifts to which our survey is most sensitive ( @xmath39 to 3 ) . this estimation was based on both numerical simulations and extrapolations of co emission properties of high redshift galaxies from , e.g. , measures of dust luminosities or star formation rates ( see decarli et al . 2016a for more details ) . if the co luminosity function is relatively flat at low luminosities , and steep at high luminosities , then galaxies around the knee of the curve dominate the overall luminosity . for example , using the popping et al . ( 2016 ) and lagos et al . ( 2012 ) co luminosity functions and our limits at 99ghz , we estimate that we should be detecting between 40% and 70% of the total co luminosity ( decarli et al . 2016 ) in this dominant redshift range . as stated in section 1 , millimeter line intensity mapping experiments will have broad impact , from studies of galaxy formation to the baryon acoustic oscillations . in this section we consider in some detail our results in the context of one topical area that has seen considerable attention recently , namely , the spectral distortions of the cmb . in section 2 , we reviewed the predictions for the line brightness at 99ghz and 242 ghz based on phenomenological calculations using on proxies for the line luminosity ( such as the cosmic star formation density ) , or numerical simulations of galaxy formation . predictions vary significantly , but range from @xmath40k to @xmath6k , in the frequency ranges being considered . to within the uncertainties inherent in small volume surveys , our direct measurements of @xmath2k at 99ghz and @xmath41k at 242ghz , argue for the faint end of these predictions , although we again emphasize that these should be treated as lower limits . how do our measurements then compare to , for instance , the expected distortions in the cmb spectrum due to early energy release , and to the expected sensitivity of planned cmb spectral distortion experiments ? as a benchmark for experimental sensitivity , we adopt the current parameters being considered for pixie ( kogut et al . 2014 ; 2011 ) , using the 15 ghz spectral resolution for the proposed experiment . considering the expected sky brightness contributions , we focus on the more cosmologically relevant predictions , relating to recombination and reionization . we note that there are other potentially significant foregrounds , in particular , galactic and extragalactic thermal emission from warm dust , and synchrotron emission . kogut et al . ( 2014 ) review the relative magnitude of these contributions . the thermal emission from warm dust , in particular , is calculated to be an order of magnitude , or more , stronger than the summed millimeter line emission considered herein . however , the spectral behavior of the dust emission is considered to be well understood , and should be well modelled , and removed , using spectral fitting algorithms over a broad frequency range . herein , we focus on the millimeter and sub - millimeter line emission , given that this is our measured quantity , and compare it to the predicted cosmological signals . additional discussion of foregrounds can be found in , e.g. , de zotti et al . ( 2015 ) . -distortion with @xmath42 . contributions from the hot gas in low mass halos give rise to a noticeable relativistic temperature correction . for the damping signal , we plot a @xmath0-distortion with @xmath43 . the cosmological recombination radiation was computed using cosmospec . the estimated effective sensitivity ( @xmath44 ) of pixie is shown for comparison ( dotted line ) . ] in fig . 3 , we show a comparison of various distortion signals , along with the line limits derived herein . we focus on _ guaranteed _ distortions within @xmath45cdm ( see chluba , 2016 , for most recent overview ) , some of which should be detectable with future experiments , at least in terms of raw sensitivity ( kogut et al . 2011 ) . a wider range of range of energy release processes ( e.g. , decaying particle scenarios ) is discussed in chluba 2013 and chluba & jeong , 2014 . the largest cmb expected spectral distortion is created at low - redshift by the reionization and structure formation process ( sunyaev & zeldovich , 1972 ; hu et al . , 1994a ) . this signal is close to a pure compton-@xmath46 distortion ( zeldovich & sunyaev , 1969 ) caused through partial up - scattering of cmb blackbody photons by hot electrons yielding a @xmath46-parameter @xmath47 ( e.g. , refregier et al . 2000 ; hill et al . , 2015 ) . contributions from the hot gas ( @xmath48 ) residing in low mass halos also give rise to a noticeable relativistic temperature correction , which could be used to constrain the average temperature of baryons at low redshifts ( hill et al . while the relativistic correction signal requires a removal of the integrated co emission , the non - relativistic @xmath46-distortion contribution should be less affected and already separable using multi - frequency capabilities of future experiments . another inevitable distortion is created by the dissipation of small - scale fluctuations in the primordial photon - baryon plasma ( sunyaev & zeldovich , 1970 ; daly , 1991 ; hu et al . , 1994b ; chluba , khatri , & sunyaev 2012 ) due to silk damping . we illustrate the @xmath0-distortion ( sunyaev & zeldovich , 1970 ) contribution of this signal using @xmath49 , which is close to the value expected for the @xmath45cdm cosmology ( chluba , 2016 ) . a @xmath0-distortion can only be created in dense and hot environments present in the early universe at @xmath50 ( burigana et al . , 1991 ; hu & silk , 1993 ) . by detecting this signal one can probe the amplitude of perturbations at scales far smaller than those seen in the cmb anisotropies , delivering another independent way to test different inflation models ( e.g. , chluba , khatri , & sunyaev 2012 ; chluba , erickcek & ben - dayan , 2012 ; dent et al . , 2012 ; clesse et al . , 2014 ) . finally , we show the cosmological hydrogen and helium recombination radiation emitted at @xmath51 ( zeldovich et al . , 1968 ; peebles , 1968 ; dubrovich , 1975 ; kholupenko et al . , 2005 ; rubio - martn et al . , 2006 ; chluba & sunyaev 2006 ) , which was computed using cosmospec ( chluba & ali - hamoud , 2016 ) . this signal could provide an independent way to constrain cosmological parameters and directly map the recombination history ( sunyaev & chluba , 2009 ) . it is unpolarized and its unique spectral variability is very hard to mimic by other foregrounds or instrumental effects . the latter two effects cause fractional spectral distortions in the range of 10@xmath52 to 10@xmath53 , implying observed brightness temperature perturbations @xmath54 , well below the contribution of the mean line brightness measured herein . thus , beyond doubt , an extraction of these primordial distortions will be very challenging , requiring sophisticated foreground removal techniques , unprecedented control of systematics , broad spectral coverage and high sensitivity multi - frequency capabilities . to successfully remove the integrated millimeter and submillimeter line emission , it will be advantageous to exploit the synergies between future cmb distortion measurements and observations similar to those presented here . given the importance of the primordial distortion signals to studies of early - universe physics , this direction is highly relevant . as alma attains full capability , spectral deep fields will become more efficient and effective , eventually encompassing areas of tens of square arcminutes . our pilot studies have already shown the impact of such measurements over a broad range of problems in modern astrophysics and cosmology . in parallel , the jansky very large array is exploring similar deep spectral searches at 30ghz ( eg . lentati et al . 2015 ; riechers et al . in prep . ) , while the advent of high frequency spectral cameras on the green bank telescope provide a sensitive platform for wide field spectral searches ( sieth et al . 2016 ) . in the long term , a next generation very large array, operating between 20ghz and 115ghz with octave , or broader , bandwidth receivers and ten times the collecting area of alma and the jvla , has the potential to revolutionize blind searches for molecular gas in the early universe ( carilli et al . 2015 ; casey et al . 2015 ) . we thank the referee for useful comments that improved the paper . fw acknowledges support through erc grant cosmic dawn . ma acknowledges partial support from fondecyt through grant 1140099 . support for rd was provided by the dfg priority program 1573 ` the physics of the interstellar medium ' . dr acknowledges support from the national science foundation under grant number ast-#1614213 to cornell university . fb acknowledges support by the collaborative research council 956 , sub - project a1 , funded by the deutsche forschungsgemeinschaft ( dfg ) . this paper makes use of the following alma data : ads / jao.alma#2013.1.00146.s and ads / jao.alma#2013.1.00718.s . alma is a partnership of eso ( representing its member states ) , nsf ( usa ) and nins ( japan ) , together with nrc ( canada ) , nsc and asiaa ( taiwan ) , and kasi ( republic of korea ) , in cooperation with the republic of chile . the joint alma observatory is operated by eso , aui / nrao and naoj . the national radio astronomy observatory is a facility of the national science foundation operated under cooperative agreement by associated universities , inc .
we present direct estimates of the mean sky brightness temperature in observing bands around 99ghz and 242ghz due to line emission from distant galaxies . these values are calculated from the summed line emission observed in a blind , deep survey for spectral line emission from high redshift galaxies using alma ( the aspecs survey ) . in the 99 ghz band , the mean brightness will be dominated by rotational transitions of co from intermediate and high redshift galaxies . in the 242ghz band , the emission could be a combination of higher order co lines , and possibly [ cii ] 158@xmath0 m line emission from very high redshift galaxies ( @xmath1 to 7 ) . the mean line surface brightness is a quantity that is relevant to measurements of spectral distortions of the cosmic microwave background , and as a potential tool for studying large - scale structures in the early universe using intensity mapping . while the cosmic volume and the number of detections are admittedly small , this pilot survey provides a direct measure of the mean line surface brightness , independent of conversion factors , excitation , or other galaxy formation model assumptions . the mean surface brightness in the 99ghz band is : @xmath2k . in the 242ghz band , the mean brightness is : @xmath3k . these should be interpreted as lower limits on the average sky signal , since we only include lines detected individually in the blind survey , while in a low resolution intensity mapping experiment , there will also be the summed contribution from lower luminosity galaxies that can not be detected individually in the current blind survey .
this work is motivated by our earlier studies @xcite of physically observable properties of sinai - ruelle - bowen ( srb ) measures for 2d periodic lorentz gases ( sinai billiards ) with finite horizon , under small perturbations . sinai billiards and their perturbations have some rough singularities , but on the other hand they are strongly hyperbolic @xcite . precisely , their lyapunov exponents are non - zero and unstable vectors grow uniformly , at a rate @xmath0 , where @xmath1 is the collision counter and @xmath2 the so called hyperbolicity constant . while sinai billiards are equilibrium systems preserving a smooth ( liouville ) measure , their perturbations are non - equilibrium systems whose natural invariant measures ( steady states ) are usually singular they are srb measures . an srb measure is an ergodic invariant probability measure with absolutely continuous conditional distributions on unstable manifolds . srb measures are the only physically observable measures because their basins of attraction have positive lebesgue volume ; see @xcite and ( * ? ? ? perturbations of sinai billiards have unique srb measures , which are mixing and bernoulli @xcite . in @xcite we studied particularly interesting perturbations of sinai billiards where the particle moved under a small constant external field @xmath3 subject to a gaussian thermostat that kept its speed constant . for that model , the srb measure was constructed long ago @xcite , and it was proved that the ( global ) current @xmath4 of the particle satisfied @xmath5 , with the conductivity @xmath6 given by a standard green - kubo formula . in that model , as well as in many other perturbations of sinai billiards , the srb measure is singular with respect to the lebesgue measure ( the hausdorff dimension of the srb measure is lower than that of the phase space @xcite ) . it is also argued in statistical mechanics that many multiparticle systems ( gases and fluids ) under external forces develop nonequilibrium steady states that behave as srb measures , in particular they are singular with respect to the phase volume ( this is known as `` chaotic hypothesis '' or `` axiom c '' @xcite ) . however one rarely observes the a steady state on the entire phase space to see its singularity . usually one observes selected variables , such as positions or velocities of certain moving particle(s ) . and computer simulations show that those selected variables have surprisingly continuous distributions . in @xcite we showed that for the lorentz gas model three selected variables the local particle density , the local current , and the angular velocity distribution have continuous densities . we derived green - kubo type formulas for those densities . in @xcite we only sketched the arguments and presented numerical evidence supporting our conclusions . in this paper we provide full mathematical proofs and generalize our conclusions to wider classes of perturbations and selected variables . our work is an extension of papers @xcite and @xcite , and for consistency we follow their definitions and notations whenever possible . we also refer the reader to these papers for more details on the model . let @xmath7 be a 2d torus without a finite union of disjoint open convex domains @xmath8 whose boundary is @xmath9 smooth and has non - vanishing curvature . two particular tables of that sort are shown in figure [ pic : tables ] . [ cols="^,^,^ " , ] a particle moves in @xmath10 according to equations @xmath11 where @xmath12 is a stationary ( independent of time ) force . collisions with obstacles are elastic ( the speed is preserved ) and specular ( the angle of reflection is equal to the angle of incidence ) . we are studying this model under three assumptions on the geometry of the table and the force : * assumption a ( additional integral ) . * a smooth function @xmath13 is preserved by the dynamics , @xmath14 is a compact 3d manifold , and for every @xmath15 and @xmath16 the ray @xmath17 intersects @xmath18 in exactly one point . under this assumption , @xmath18 can be parameterized by @xmath19 where @xmath20 is the position on the torus and @xmath21 is the angle of motion measured between @xmath22 and the positive @xmath23-axis . equations of motion can now be given as @xmath24 where @xmath25 note that @xmath26 does not have to be constant , but it is bounded away from @xmath27 and infinity : @xmath28 ( due to the compactness of @xmath18 ) . for a function @xmath29 on @xmath18 let @xmath30 , @xmath31 , @xmath32 denote its partial derivatives , and @xmath33 the maximum of @xmath29 and its first and second partial derivatives over @xmath18 . let @xmath34 . * assumption b ( smallness of the force ) . * the force @xmath35 and its first derivatives are small : @xmath36 more precisely , we require that for any given @xmath37 there is a small @xmath38 such that all our results hold whenever @xmath39 and @xmath40 . * assumption c ( finite horizon ) . * there is an @xmath41 so that every straight line on the torus of length @xmath42 crosses the interior of at least one obstacle . ( both tables a and b in figure [ pic : tables ] have finite horizon . ) a particular example of the force is _ gaussian thermostat _ , which was the subject of paper @xcite , being a physically interesting model of electrical conductance . there @xmath43 , thus @xmath44 is preserved by the dynamics . for more examples see ( * ? ? ? * section 2 ) . @xmath45 acts on the _ phase space _ @xmath18 , which is a 3d manifold . _ collision space _ @xmath46 is a set of points where the particle undergoes a collision with @xmath47 . now @xmath48 can be parameterized by @xmath49 where @xmath50 is an arclength parameter along @xmath47 and @xmath51 is an angle between the particle s outgoing velocity and the inward normal to @xmath52 . note that @xmath53 ( see @xcite ) , thus @xmath54 can be identified with a finite union of cylinders @xmath55 $ ] , hence the collision space is independent of the force @xmath35 . _ collision map _ @xmath56 is the natural first return map on @xmath48 . it preserves a unique srb measure @xmath57 ; see @xcite . we denote the time between collisions by @xmath58 . now @xmath45 can be represented as a suspension flow with base @xmath48 and the ceiling function @xmath59 . the flow @xmath45 preserves a unique srb measure @xmath60 ; see @xcite . the map @xmath61 and the flow @xmath45 are ergodic , mixing , and bernoulli , they enjoy strong statistical properties @xcite . we will use subscript `` 0 '' in @xmath62 , @xmath63 , @xmath64 , @xmath65 etc . to refer to the unperturbed ( billiard ) dynamics on @xmath66 , i.e. , to the case @xmath67 . there is a simple relation between @xmath60 and @xmath57 : if @xmath68 is a bounded function such that @xmath69 , then @xmath70 in addition to natural singularities of @xmath61 ( the preimages of grazing collisions characterized by @xmath71 ) we need to cut @xmath48 into countably many _ homogeneity strips _ along the lines @xmath72 for all @xmath73 , forcing @xmath61 to be discontinuous on the preimages of these lines as well ; see @xcite . collision space @xmath48 has a measurable partition into _ homogeneous unstable manifolds _ ( or h - fibers ) that are increasing curves in the @xmath74 coordinates with slopes uniformly bounded away from @xmath27 and @xmath75 and uniformly bounded curvature . h - fibers end on _ singularity curves _ that are images of the lines @xmath76 and boundaries of the homogeneity strips . it is important for us that the singularity curves are nondecreasing in @xmath49 coordinates and there are countably many of them . for almost every point @xmath77 ( with respect to both the lebesgue measure on @xmath48 and the srb measure @xmath57 ) there exists an h - fiber @xmath78 that contains @xmath79 . the srb measure @xmath57 on @xmath48 may be singular with respect to the lebesgue measure , but its conditional distributions on h - fibers are absolutely continuous with respect to the arclength measure . for @xmath80 we define the future separation time @xmath81 as the first @xmath82 for which @xmath83 and @xmath84 belong to different connected components of @xmath48 . similarly , @xmath85 is the first @xmath82 for which @xmath86 and @xmath87 belong to different connected components of @xmath48 . a function @xmath88 is _ dynamically hlder continuous _ if there are @xmath89 and @xmath90 such that for any @xmath79 and @xmath91 lying on one unstable curve for some positive constants @xmath92 . note that unstable curves are defined on @xmath54 before it is cut into connected components , i.e. , they can cross singularity lines and borders of the homogeneity strips . ] @xmath93 and for any @xmath79 and @xmath91 lying on the same stable curve @xmath94 dynamical hlder continuity implies boundedness of @xmath29 . the class of dynamically hlder continuous functions is large , for example it includes all piecewise hlder - continuous functions whose discontinuities coincide with those of @xmath95 for some @xmath96 . we will say that a function @xmath97 is _ regular _ on an unstable curve @xmath98 if @xmath99 where @xmath100 and @xmath101 is a sufficiently large constant that is determined by the geometry of the table and can be chosen arbitrarily high . a _ standard pair _ is @xmath102 is an unstable curve @xmath98 with a probability measure @xmath103 on it which has a regular density with respect to the arclength measure . more generally , a _ standard family _ is an arbitrary collection @xmath104 , @xmath105 , of standard pairs with a probability factor measure @xmath106 on the index set @xmath107 ( one can naturally define a metric on the space of all standard pairs , see ( * ? ? ? * proposition 8.1 ) , then @xmath107 becomes a metric space with the respective borel @xmath6-algebra ) . every standard family @xmath108 naturally induces a measure on @xmath48 by @xmath109 every point @xmath79 on the unstable curve @xmath110 breaks it into two pieces . denote by @xmath111 the length of the shorter one . let @xmath112 a standard family @xmath108 is * proper * if @xmath113 where @xmath114 is a large but fixed constant . a standard family consisting of all h - fibers together with the conditional measures induced by @xmath57 is proper @xcite . we will show that despite the singularity of the srb measure with respect to the lebesgue measure , its projections that are _ transverse _ to the unstable manifolds have continuous densities . the collision space @xmath48 admits a measurable partition @xmath115 into h - fibers @xmath116 . the srb measure @xmath57 induces conditional probability measures @xmath103 on h - fibers @xmath117 and a factor measure @xmath118 on @xmath115 with a standard @xmath6-algebra ( see , e.g. , @xcite ) . the measures @xmath103 are absolutely continuous with respect to the arclength on @xmath98 . moreover , the corresponding density functions @xmath119 are @xmath120 smooth ( see , e.g. , ( * ? ? ? 5.2 ) ) and regular as defined above . the length of h - fibers , as a function @xmath121 is measurable by the dominated convergence theorem : for almost every @xmath122 let @xmath123 be a connected component of the domain of @xmath124 which contains @xmath79 . let @xmath125 be a supremum of lengths of h - fibers in @xmath123 . then @xmath126 ( see the beginning of chapter 5 in @xcite for more information on the structure of @xmath115 . ) hence the length of h - fibers is also a measurable function on @xmath115 , by a straightforward verification . since @xmath115 is a proper standard family , @xmath127 , and therefore ( * ? ? ? 7.4 ) @xmath128 this allows us to renormalize the conditional measures and the factor measure replacing @xmath129 and @xmath130 as follows : @xmath131 the new factor measure @xmath132 is still finite , according to . since @xmath103 is a probability measure for each @xmath98 , and @xmath119 is @xmath120 smooth and regular , @xmath119 is bounded by @xmath133 from below and by @xmath134 from above , and thus the density @xmath135 of the new measure @xmath136 is also @xmath120 smooth and bounded _ uniformly _ by @xmath137 and @xmath138 . [ lm4.1 ] the @xmath57-measure of every h - fiber @xmath117 is zero , i.e.@xmath139 . assume that an h - fiber @xmath98 has positive measure . recall that @xmath119 is bounded away from @xmath27 by @xmath133 . note that the collision map @xmath61 is piecewise continuous and bijective . for every @xmath140 the curve @xmath141 is a piece of some h - fiber ; it carries the same measure as @xmath98 , but its length is @xmath142 . by the poincar recurrence theorem @xmath143 must overlap with @xmath98 infinitely many times , which implies that the measure of a relatively long piece of @xmath98 is equal to the measure of an arbitrarily short piece , hence density @xmath119 can not be bounded . in the following theorem @xmath144 denotes an abstract manifold , but @xmath115 is still the partition of our collision space @xmath54 and @xmath145 is still the factor measure defined above . [ topx ] let @xmath144 be a compact riemannian manifold equipped with lebesgue measure @xmath146 . assume that for each @xmath117 there is a function @xmath147 , which is bounded uniformly in @xmath98 . define a ( possibly signed ) measure @xmath148 on @xmath144 by @xmath149 where we assume that @xmath150 is measurable , as a function of @xmath98 , for every measurable @xmath151 . assume that for every point @xmath152 @xmath153 then the measure @xmath148 has a continuous density on @xmath144 with respect to @xmath146 . if , in addition , for every @xmath152 @xmath154 then the density of @xmath148 is strictly positive and bounded away from zero . for @xmath155 and @xmath156 let @xmath157 denote the ball of radius @xmath50 centered at @xmath23 and @xmath158 its lebesgue volume . then for @xmath145-almost every @xmath117 @xmath159 by the bounded convergence theorem @xmath160 is a measurable function on @xmath115 and @xmath161 by the lebesgue differentiation theorem @xmath162 is almost everywhere on @xmath144 equal to the density of @xmath148 . the continuity and positivity of @xmath162 under our assumptions follows directly from the bounded convergence theorem . next we show how theorem [ topx ] implies the continuity of various projections of the srb measure @xmath57 . in all our cases , every @xmath163 will be a discontinuity point for at most countably many functions @xmath160 . this , along with lemma [ lm4.1 ] , will guarantee the assumption . let @xmath164 $ ] and @xmath165 be the projection onto the @xmath51-coordinate . let @xmath148 be the corresponding pushforward of @xmath57 . [ tmad ] the measure @xmath148 is absolutely continuous on @xmath164 $ ] with a positive continuous density . for @xmath151 we have @xmath166 and @xmath167 since the h - fibers are increasing curves in the @xmath74 coordinates with slopes uniformly bounded away from @xmath27 and @xmath75 and the densities @xmath168 of the respective measures @xmath169 are uniformly bounded , all the measures @xmath170 have uniformly bounded piecewise continuous densities on @xmath144 ( the densities of @xmath170 correspond to @xmath171 in theorem [ topx ] ) . recall that the h - fibers terminate on singularity curves , and every line @xmath172 intersects at most countably many singularities . thus at most countably many unstable manifolds terminate on that line , hence at most countably many projected densities have discontinuities at any given @xmath173 . this guarantees , and follows from ( * ? ? ? * lemma 3.3 ) because the preimage of each line @xmath172 is a finite union of stable curves . for every measurable @xmath174 , the measurability of the function @xmath175 follows from the measurability of the partition @xmath115 . now the result follows from theorem [ topx ] . exactly the same argument shows that projection onto the @xmath50 coordinate has a positive continuous density . we leave the collision space @xmath48 and project the srb measure @xmath60 for the flow @xmath45 onto the table @xmath10 . let @xmath176 be the projection of the phase space onto the configuration space , and @xmath148 be the pushforward of @xmath60 . the measure @xmath148 is absolutely continuous on @xmath10 with a positive continuous density . according to formula ( [ munu ] ) , for any set @xmath177 @xmath178 @xmath179 therefore @xmath180 we observe that the map @xmath181 defines a measure on @xmath66 with a piecewise continuous density . this measure is supported on the _ trace _ of h - fiber @xmath98 ( see figure [ unstable - table ] ) , on which the density is positive and continuous . this density corresponds to @xmath171 in theorem [ topx ] . the densities @xmath171 on @xmath10 are bounded uniformly in @xmath98 because the density of @xmath169 on each @xmath98 is uniformly bounded . is supported on trajectories that start from an h - fiber @xmath98 ] furthermore , for any @xmath183 define the set @xmath184 of points in the collision space . the trajectories starting from @xmath185 pass through @xmath23 and therefore correspond to a focusing wave front ( * ? ? ? 3.7 ) . in other words , @xmath185 consists of a finite number of decreasing curves in the @xmath49-coordinates , which have countably many intersections with singularity curves on which h - fibers terminate . recall that h - fibers also terminate on the preimages of lines @xmath186 . it is clear that if @xmath187 is a point of discontinuity for the density @xmath171 of some h - fiber @xmath98 , then @xmath98 must terminate on @xmath185 . therefore @xmath23 can be a point of discontinuity for at most countably many densities @xmath171 . this guarantees , and again follows from ( * ? ? ? * lemma 3.3 ) because @xmath185 is a finite union of stable curves . now the result follows from theorem [ topx ] . note that the density of the measure @xmath148 on @xmath10 is given by @xmath188 next we show that the velocity field is continuous in the following sense . for every point @xmath189 let @xmath190 denote the average velocity vector , where @xmath191 denotes the conditional measure induced by @xmath60 on the section of the phase space @xmath18 corresponding to the fixed footpoint @xmath15 . the velocity vector field @xmath192 is continuous on @xmath66 . in place of the srb measure for the flow @xmath60 we use a signed measure @xmath193 , defined by @xmath194 for any function @xmath195 on @xmath18 , where @xmath196 is the horizontal component of the velocity of the particle at @xmath197 . then the projection of @xmath193 onto @xmath10 is a signed measure @xmath198 defined by @xmath199 @xmath200 and @xmath201 once again , the map @xmath202 defines a ( signed ) measure on @xmath10 with density @xmath203 that has the same properties as @xmath171 above , so that theorem [ topx ] applies to prove that @xmath198 has continuous a density on @xmath10 given by @xmath204 note that the average horizontal velocity on the set @xmath205 is given by @xmath206 . taking into account that @xmath148 and @xmath198 have continuous densities @xmath26 and @xmath207 , and @xmath208 everywhere , the average horizontal velocity at every point @xmath209 is well defined as @xmath210 and is continuous . the same argument works for the vertical component of the velocity . figure [ pic : velocity ] shows the computed velocity field in a system with a gaussian thermostated force @xmath35 directed horizontally to the right . ) .[pic : velocity],title="fig:",scaledwidth=48.0% ] ) .[pic : velocity],title="fig:",scaledwidth=48.0% ] this section is restricted to a specific model a constant external field with gaussian thermostat . the force is given by @xmath211 , where @xmath3 is a small nonzero constant vector . this model was the subject of our paper @xcite . we can choose the coordinate system so that @xmath3 points in the positive @xmath23 direction , then @xmath212 $ ] ( see assumption a ) measures the angle between the particle velocity and the field @xmath3 . it is a direct verification that the only straight trajectories ( where @xmath213 ) are those parallel to the field @xmath3 , i.e. , @xmath214 . this fact is used in the construction below . let @xmath215 $ ] , denote by @xmath216 the projection of the phase space onto the @xmath21 coordinate , and by @xmath148 the pushforward of @xmath60 . the measure @xmath148 is absolutely continuous on @xmath144 with a positive continuous density . for every set @xmath217 we have : @xmath218 @xmath219 denote @xmath220 and let @xmath221 be the projection of @xmath222 on @xmath144 . then for any set @xmath223 @xmath224 let @xmath225 be again the _ trace _ of @xmath98 . then @xmath226 is supported on @xmath227 and has continuous and uniformly ( in @xmath98 ) bounded density on it . since @xmath227 is a compact smooth 2-dimensional manifold in the phase space @xmath18 and h - fibers correspond to _ _ strongly divergent families of trajectories _ _ denote the curvature of a cross - section of @xmath227 orthogonal to the flow ; then _ strong divergence _ means @xmath228 for some global constants @xmath229 and @xmath230 , see ( * ? ? ? * secion 3 ) . ] , the angle between @xmath227 and the @xmath21-axis is bounded above by a global constant that is less than @xmath231 . therefore , @xmath221 has a density on @xmath144 . moreover , the area and the size ( diameter ) of @xmath227 are uniformly ( in @xmath98 ) bounded above and below by positive constants . thus the density of @xmath221 is bounded above uniformly in @xmath98 . the density of @xmath221 may have a discontinuity at @xmath232 only if @xmath227 has a curve on its boundary where @xmath233 . the boundary of @xmath227 consists of four parts : @xmath234 where @xmath235 and @xmath236 are the endpoints of @xmath98 . the angle @xmath21 can not be constant on any sub - curve of @xmath237 , because @xmath98 is an increasing curve in the @xmath49 coordinates . on @xmath238 or @xmath239 , it can be a constant only if the whole trajectory is parallel to @xmath3 , i.e. , @xmath240 . the trajectories where @xmath241 or @xmath242 make a finite union of flat wave fronts , with at most countably many intersections with singularity curves and preimages of @xmath243 , on which h - fibers terminate . hence there are at most countably many @xmath98 s for which @xmath238 or @xmath239 has a sub - curve where @xmath241 or @xmath244 . it may happen that @xmath245 contains a subset of positive length on which @xmath246const . note , however , that for every @xmath247 the set @xmath248 of reflection points where the `` incoming '' velocity vector makes angle @xmath249 with the field @xmath3 , is a finite union of smooth curves , so its preimage @xmath250 is a finite union of smooth curves , too . it is now clear that there could be at most countably many @xmath98 s that partially coincide with @xmath250 . overall , for every @xmath251 there are at most countably many @xmath98 s for which the boundary of @xmath227 contains a curve on which @xmath252 . this guarantees ( [ e0 ] ) . to satisfy ( [ e1 ] ) , for every @xmath251 consider a set @xmath253 of reflection points where the `` outgoing '' velocity vector makes angle @xmath249 with the field @xmath3 . it consists of a finite number of decreasing curves , and its preimage @xmath254 consists of a finite number of stable curves . consider two sets @xmath255 it follows from ( * ? ? ? * lemma 3.3 ) that @xmath256 has positive @xmath145-measure in @xmath115 , and @xmath257 is at most countable , because it has at most countably many intersection points with singularity curves and preimages of @xmath258 , on which h - fibers terminate . therefore , @xmath259 . observe that for every @xmath260 the density of the projected measure @xmath221 is positive at @xmath249 . this implies ( [ e1 ] ) . now the result follows from theorem [ topx ] . figure [ pic : angular ] shows the density of @xmath148 constructed via computer simulation for a system under a small external force directed horizontally to the right , with gaussian thermostat . ) . [ pic : angular],title="fig:",scaledwidth=48.0% ] ) . [ pic : angular],title="fig:",scaledwidth=48.0% ] suppose that the force @xmath261 is parameterized by a parameter @xmath262 $ ] . more precisely , assumption b in section [ sec : model ] now takes form @xmath263 with some @xmath264 and @xmath265 independent of @xmath266 . we will add the subscript @xmath267 to our symbols to emphasize the dependence of the dynamics on @xmath267 . let @xmath268 be the jacobian of @xmath269 with respect to the unperturbed billiard invariant measure @xmath62 . denote @xmath270 for @xmath271 and assume that @xmath272 exists almost everywhere with respect to @xmath62 . we will make a rather technical , but not too restrictive assumption on functions @xmath273 , namely that each h - fiber of the map @xmath63 can be divided into no more than @xmath274 pieces ( for some constant @xmath274 ) , on which they are hlder continuous with a constant @xmath275 and exponent @xmath276 , i.e. @xmath277 , and that @xmath278 . we need exponent @xmath276 to connect @xmath273 to a proper standard family , as it will be shown further . for example , for the gaussian thermostat in section [ sec : gt ] , the function @xmath273 satisfies our assumptions with hlder exponent @xmath279 , and constant @xmath280 determined by the maximum and minimum curvature of the obstacles ; see ( * ? ? ? * sect . assume that we are observing a function @xmath281 on @xmath48 that may also change with @xmath267 . let @xmath281 be bounded uniformly in @xmath267 and dynamically hlder continuous with respect to @xmath269 , with constants @xmath282 and @xmath283 independent from @xmath267 . suppose the limit @xmath284 exists almost everywhere with respect to @xmath62 . @xmath285 it may not be true that @xmath286 , this part of response is determined by the character of @xmath281 . we start with a kawasaki - type formula ( * ? ? ? * eq . ( 2.15 ) ) : @xmath287.\ ] ] here terms of the series decay exponentially fast and uniformly in @xmath267 . we are going to factor @xmath267 out of the series and prove that we still have a series with terms converging to zero exponentially and uniformly in @xmath267 . note that the integrands @xmath288 are bounded and pointwise converge to @xmath289 , as @xmath290 . therefore it is enough to show that there exist constants @xmath291 and @xmath292 so that @xmath293 \right| \leq c \theta^k$ ] for every @xmath294 . we decompose @xmath273 into @xmath295 where @xmath296 and @xmath297 . then @xmath298 since @xmath299 . let @xmath98 be a piece of an h - fiber corresponding to the unperturbed dynamics , on which @xmath273 is hlder continuous with constant @xmath280 and exponent @xmath276 , and @xmath300 be its subcurve that terminates at points @xmath79 and @xmath91 . then @xmath301 where constant @xmath302 is determined by the billiard geometry , see ( * ? ? ? * formula ( 5.32 ) ) , and @xmath303 comes from ( [ eq : regular ] ) . if @xmath304 is the density of the conditional measure induced by @xmath62 on @xmath98 , then @xmath305 where constant @xmath101 also comes from ( [ eq : regular ] ) . we are free to choose @xmath101 arbitrarily large , and replacing @xmath101 with @xmath306 we make @xmath307 a regular function on @xmath98 . thus the densities @xmath307 on the pieces of h - fibers , where @xmath273 is continuous , specify standard families @xmath308 such that @xmath309 for every function @xmath310 . the standard family @xmath311 consisting of all h - fibers with their conditional measures corresponding to the unperturbed dynamics , is proper , i.e. , @xmath312 ; see equation ( [ eq : zg ] ) . we want to show that @xmath308 is also proper . to each standard pair @xmath313 there correspond at most @xmath274 standard pairs @xmath314 in @xmath308 with regular densities . then , in the notations of equation ( [ eq : zg ] ) , @xmath315 therefore @xmath316 . we are now free to choose @xmath114 large enough to make the standard families @xmath308 proper . by the equidistribution property ( * ? ? ? * proposition 2.2 ) @xmath317 where @xmath318 and @xmath319 are independent from @xmath267 . coupled with @xmath320 = \nu_0\left(\delta_{\varepsilon}^+\right ) \left ( \nu_{\mathcal{g}_{\varepsilon}^+ } \left(f_{\varepsilon}\circ \mathcal{f}_{\varepsilon}^k\right ) - \nu_{\mathcal{g}_{\varepsilon}^- } \left(f_{\varepsilon}\circ \mathcal{f}_{\varepsilon}^k\right ) \right)\ ] ] this gives @xmath320 \leq 2 \nu_0\left(\delta_{\varepsilon}^+\right)c_8 \theta_8^k \text{.}\ ] ] we note that @xmath321 , which completes the proof . we proved the linear response formula for the map @xmath269 but not for the flow , because no estimates on correlations for perturbed billiard flows are available . the authors are partially supported by nsf grant dms-0969187 . we are grateful to the alabama supercomputer administration for computational resources . we are grateful to the anonymous reviewers for the very thorough job they have done . the paper significantly improved due to their suggestions .
sinai - ruelle - bowen measures are the only physically observable invariant measures for billiard dynamical systems under small perturbations . these measures are singular , but as it was noted in @xcite , marginal distributions of spatial and angular coordinates are absolutely continuous . we generalize these facts and provide full mathematical proofs .
we consider a singlelocus ( the a locus ) that has two alleles ( a 1 and a 2 ) . we assume the locus can have direct and/or maternal effects on offspring phenotypes ( including fitness ) . thus , our model allows for the presence of pleiotropy between direct and maternal effects , while providing a model that considers only either direct or maternal effects by simply setting one set of parameters to zero ) . there is a large body of evidence suggesting that genes with both direct and maternal genetic effects are likely to be common in eukaryotes . in early embryos it is common to find that a large fraction of the proteincoding genome is represented as maternal mrnas ( ca . 40% in the mouse , 50% in the flour beetle , tribolium castaneum [ preuss et al . 2012 ] , and 65% in the fruit fly , drosophila melanogaster [ tadros and lipshitz 2009 ] ) , providing opportunities for a large fraction of the genome to have both direct and maternal effects . likewise , empirical estimates of genetic correlations between direct and maternal effects , which presumably primarily reflect loci with pleiotropic direct and maternal effects , are typically large ( robinson 1996 ; roff 1997 ; wolf and brodie iii 1998 ; wilson and reale 2006 ) , and mapping studies of maternal effects have directly demonstrated that such pleiotropy can be common ( casellas et al . although we use a singlelocus system to explore the properties of direct and maternal effects , in the supplementary material we demonstrate that , as with the classic single locus model of direct effects , the results extend to a multilocus system when selection is weak enough that the population remains in quasilinkageequilibrium ( qle ) ( kimura 1965 ; nagylaki 1976 , 1993 ) . throughout , we view the genotypephenotype relationship and fitness from the perspective of the offspring because it determines how selection at the level of the individual ( i.e. , offspring ) drives evolutionary dynamics ( kirkpatrick and lande 1989 ; cheverud and wolf 2009 ) . the effects of the locus are summarized using two classic parameters , the additive ( a ) and dominance ( d ) genotypic values or effects ( see falconer and mackay 1996 ) . following wolf and cheverud ( 2012 ) , we define the direct and maternal effects of the locus in an idealized scenario where each is measured in the absence of the other effect . we take this approach ( of defining each in the absence of the other ) because , in the traditional quantitative genetic approach , direct , and maternal effects are partially confounded due to relatedness ( i.e. , the fact that some genotypes of mothers can only produce a subset of possible offspring genotypes ; e.g. , a 1 a 1 mothers can not have a 2 a 2 offspring ) . our definitions of direct and maternal effects are therefore equivalent to the values that one might recover through crossfostering , where offspring genotypes are randomized across maternal genotypes ( wolf and cheverud 2012 ) . we use the subscripts o and m to indicate direct ( offspring ) and maternal effects , respectively . the additive direct effect genotypic value , ao , is defined as half the difference between the phenotypic values of the a 1 a 1 and a 2 a 2 genotypic classes ( falconer and mackay 1996 ) and the dominance direct effect genotypic value , do , as the deviation of the heterozygote phenotypic value from the unweighted average of the phenotypic values of the homozygotes in the absence of maternal effects . analogously , the additive maternal effect genotypic value , am , , is half the difference between the mean phenotypes of the offspring of a 1 a 1 and a 2 a 2 mothers , while the dominance maternal effect genotypic value , dm , is defined as the deviation of the average offspring phenotype of heterozygous mothers from the average of the offspring means of homozygous mothers , in the absence of direct effects ( cf . wolf and cheverud 2012 ) . the offspring phenotypes as a function of these genetic effects are summarized in table 1 . the phenotype ( or fitness ) of offspring as a function of their genotype and the genotype of their mother offspring genotypes have alleles ordered by their parentoforigin , with the maternally inherited allele appearing first , whereas maternal genotypes are unordered ( since the values are identical for the maternal genotype reciprocal heterozygotes ) . marginal means are given for each maternal and offspring genotype for the case without inbreeding ( see table s1 for the values under inbreeding ) . cells containing a indicate combinations that do not exist ( after table 4 in wolf and cheverud 2012 ) . for simplicity , we let the parameters p 1 and p 2 describe allele frequencies of the a 1 and a 2 alleles , respectively , in both parents and offspring , and therefore they can be used to calculate the frequencies of the various maternaloffspring genotype combinations ( table 2 ) . hence , in the presence of selection , they describe the frequency of alleles after selection in the parental generation and before selection in the offspring generation . initially , we assume random mating but relax this assumption later in our modeling when we consider the influence of inbreeding ( the frequency values in table 2 apply for both the case with and without inbreeding ) . we assume selection is weak enough that genotypes remain in hardy weinberg proportions ( i.e. , quasi hardy weinberg proportions , qhw , see nagylaki 1976 , table 1 , and supplementary material ) , except where we model deviations from hardy weinberg proportions associated with inbreeding . this allows us to describe the distributions of parental and offspring genotypes as a simple function of allele frequencies ( p 1 and p 2 ) with minimal loss of generality . by doing so we can formalize the problem and provide simple analytical results that capture the basic properties of genes with direct and maternal effects . those basic properties do not change substantively as we add loci or deviate from h w equilibrium ( hwe)those processes simply add a small degree of error around predictions . in the supplementary material we analyse the nature of the error associated with the assumptions of quasihardy weinberg equilibrium ( qhw ) and quasilinkageequilibrium ( qle ) . the frequencies of the maternaloffspring genotype combinations before selection genotypes have alleles ordered by their parentoforigin , with the maternally inherited allele appearing first . the combinations are a function of the frequency of the four ordered genotypes ( fij , where i is the maternally inherited allele ) and the frequencies of the offspring genotypes within the maternal genotypes ( uij , where again i is the maternally inherited allele ) . the frequencies of the ordered genotypes ( fij ) appear at the bottom of the columns for the offspring genotypes ( the genotype frequencies are the same as those of the four possible maternal genotypes and so are only listed under the offspring genotypes for simplicity ) and the frequencies of the offspring genotypes within the maternal genotypes ( uij ) are : u11=f+p1(1f ) , u12=p2(1f),u21=p1(1f),u22=f+p2(1f ) , and cells containing a the components of genetic variance resulting from direct effects and maternal effects , in the absence of the other , are given in table 3 . these expressions are equivalent to the classic expressions of the quantitative genetics literature ( falconer and mackay 1996 ) and are presented here for comparison . using the phenotypes in table 1 and the frequencies in table 2 we can derive the additive genetic covariance ( owing to pleiotropy ) between the direct effect of an individual 's own genes and the maternal effect it experiences arising from its mother 's genes ( i.e. , the covariance between direct and indirect genetic effects on the offspring 's phenotype ) ( willham 1963 ; riska et al . 1985 ; kirkpatrick and lande 1989 ; wolf and brodie iii 1998 ) , ( 1 ) cov mo = p1p2ao+do(p2p1)am+dm(p2p1 ) . patterns of direct and maternal effect variation in randomly mating and inbreeding populations ( with the degree of inbreeding given by f ) in each case , the variation associated with direct or maternal effects is defined in the absence of the other type of effect , so that the confounding of the effects does not contribute to the pattern of variation ( see the main text for the case where both occur simultaneously ) . variation under both random mating and inbreeding is decomposed in additive ( v additive ) and dominance ( v dominance ) genetic variation , where the total is simply the sum of these components . equation ( 1 ) also represents half of the additive genetic covariance between direct and maternal effects of the locus at the individual level ( i.e. , the additive genetic relationship between the influence that individuals genes have on their own phenotype and the influence of their genes on the phenotype of their offspring is 2covmo ) ( riska et al . it is important to keep in mind that the covmo is the covariance between effects ( direct and maternal ) on the phenotypes of an individual , not a measure of the maternaloffspring covariance ( i.e. , it is not a measure of the resemblance of mothers and offspring ) . variance component models of maternal effects have shown that this covariance plays an important role in determining how maternal effects contribute to the offspring genotypephenotype relationship and , thereby , to patterns of offspring phenotypic variation ( cf . the parameter gmo in kirkpatrick and lande and cov(ao , am ) in cheverud ) . maternal effects contribute to the offspring genotype phenotype relationship because offspring experience a maternal effect arising from their mother 's genome while also inheriting half their genes from their mother . with both direct and maternal effects , the variance among unordered ( vg ) offspring genotypes ( i.e. , combining the a 1 a 2 and a 2 a 1 heterozygotes into a single heterozygote class ) equals : ( 2)vg=2p1p2(ao+12am)+(p2p1)(do+12dm)2 + 2p1p2do2=[va(o)+14va(m)+2 cov mo]+vd(o)=va+vd . from equation ( 2 ) we see that the variation among offspring genotypes , vg , includes the variance arising from additive ( va ( o ) ) and dominance direct effects ( vd ( o ) ) , as well as one fourth of the additive genetic maternaleffect variance ( va ( m ) ) , and the additive genetic covariance between direct and maternal effects , which is twice the directmaternal genetic covariance ( covmo ) . the contribution of a single locus to the total genetic variance ( eq . 2 ) can be partitioned into additive and dominance components of genetic variation ( fisher 1918 ; falconer and mackay 1996 ) . with maternal effects , the additive genetic variance among offspring genotypes contains a component contributed by maternal effects and the directmaternal genetic covariance ( covmo ) ( dickerson 1947 ) . in equation ( 2 ) , the total additive genetic variance appears as the first term in brackets , where va = va(o)+14va(m)+2 cov mo , while the dominance genetic variance is the remainder or simply the direct dominance variance ( vd = vd ( o ) ) . this result demonstrates that , in addition to the contribution of direct effects ( va ( o ) ) to the additive genetic variance , both additive maternal effects and the additive maternaloffspring covariance ( twice the directmaternal genetic covariance , eq . a trait can have heritable variation ( i.e. , va > 0 ) even when the locus does not directly affect the expression of the trait ( i.e. , va ( o ) = 0 ) because maternal effects can contribute a component of heritable variation . likewise , the trait can be affected by both direct and maternal genetic effects ( i.e. , va ( o ) > 0 and va ( m ) > 0 ) , but have no heritable ( additive genetic ) variation overall because these two effects oppose each other ( i.e. , show a negative genetic covariance ) and therefore cancel each other out ( which occurs when cov mo=12[va(o)+14va(m ) ] ) ( see also dickerson 1947 for a discussion of trait heritability ) . interestingly , equation ( 2 ) also demonstrates that maternal effects contribute only to additive variation but not to dominance variation among offspring genotypes . because the two types of homozygous mothers ( a 1 a 1 and a 2 a 2 ) can each produce only one of the two types of reciprocal heterozygotes ( a 1 a 2 and a 2 a 1 , respectively , with the maternally inherited allele appearing first ; see table 1 ) , the phenotypes of the reciprocal heterozygotes will differ when there are maternal effects ( hager et al . maternal genetic effects contribute a component of variation between the reciprocal heterozygotes that is equal to 14va(m ) . because this variation is between the heterozygote classes that are genetically identical , but differ in the parent of origin of their alleles , it appears as a type of parentoforigin dependent variation , analogous to the imprinting variance ( spencer 2002 ) . although maternal genetic effects contribute to the variance among offspring genotypes , they also contribute variation that is not associated with the offspring genotype ( cf . for example , consider an idealized scenario where a maternal effect is caused by a single locus in a population of families of fullsiblings and accounts for all variation in some trait all offspring in the same family experience the same maternal effect because they share the same mother , and so they all have the same phenotype . however , offspring with the same phenotype owing to maternal effects may have different genotypes at the maternal effect locus because there is mendelian segregation variance within families . as a result , the offspring genotype at the maternal effect locus can not fully account for variation in offspring phenotype , despite the fact that the phenotype was determined by that locus albeit in the mother ( i.e. , through a maternal effect ) . therefore , while a maternal effect can be wholly genetically determined and fully account for offspring trait variation , when we measure variation among offspring , their genotype at the maternal effect locus only accounts for a component of that trait variation . the rest of the phenotypic variation contributed by maternal genetic effects is , therefore , uncorrelated to offspring genotype , and consequently , from the perspective of the offspring a component of phenotypic variation arising from maternal genetic effects appears to be a random environmental source of variation . this is not meant to imply that maternal genetic effects are environmental variation in the sense of being caused by the ecological environment , but rather , it follows from the standard partitioning perspective in quantitative genetics in which variation that is not explained by an individual 's genotype ( i.e. , variation that is random with respect to genotype ) is lumped together in the environmental variance . as a result , even when all phenotypic variation arises from genetic influences ( i.e. , from direct or maternal genetic effects ) , there can still be a component of random environmental variation among offspring genotypes ( i.e. , phenotypic variation among offspring that is not associated with their genotype ) corresponding to : ( 3)ve = p1p2am+dm(p2p1)2 + 2p1p2dm2=12va(m)+vd(m ) . equation ( 3 ) illustrates that half of the additive genetic maternaleffect variance and , all of the dominance maternaleffect variation appear as environmental components of variation from the perspective of the offspring genotype phenotype relationship ( i.e. , these maternal genetic effects contribute variation that appears within , not among , classes of offspring genotypes , and hence is conceptually the same as other sources of environmental variation ) . this result is implied in most models of maternal effects ( e.g. , willham 1963 ; kirkpatrick and lande 1989 ) , where the contribution of maternal effects to patterns of variation and response to selection in offspring are typically weighted by a factor of , but these earlier models considered only the contribution of additive maternal effects and not maternal dominance effects that predominate in ve . because maternal effects are attributed to the genotype of the mother , they contribute a component of variation among maternal families ( i.e. , among the groups of offspring produced by the different types of mothers ) ( dickerson 1947 ) . therefore , the entire maternal effect variance ( v maternal ) , shown in table 3 , appears as an amongmaternalfamily component of variation , while the contribution of direct effects to among family variation depends on the mating structure ( e.g. , whether offspring are fullsiblings or halfsiblings etc . ) . to understand the evolutionary consequences of maternal genetic effects for selection on offspring , we assume that the genetic parameters , ao , do , am , and dm , correspond to effects on offspring fitness . as above , we assume that selection stemming from these fitness differences is sufficiently weak that it does not produce significant deviations from the hardy weinberg expectations . ( see supplementary material , where we show that the deviations from h w proportions are generally o(s ) , where s represents the strength of selection ) the mean fitness of the population equals : ( 4)w=+(p1p2)(ao+am)+2p1p2(do+dm),where is the baseline ( expected ) fitness value that is not associated with variation at the a locus . this equation for population mean fitness is often described as the adaptive landscape ( wright 1932 ; see also ; svensson and calsbeek 2012 ) ; it represents the relationship between allele frequencies and expected fitness . in standard theory , .the fitness of individuals is affected by their own trait values , but not by the trait values of other individuals in the population ( arnold 2003 , p. 368 ) . that assumption is explicitly violated here where genes in the maternal genome affect the offspring trait value and fitness . regardless of whether this assumption is met , peaks on the adaptive landscape occur where the partial derivative of mean fitness ( w ) with respect to the frequency of either of the alleles is zero ( e.g. , when w/wp1p1=0 ) . taking the partial derivative of mean fitness in equation ( 3 ) with respect to p 1 and setting it equal to zero yields : ( 5)p1wp1=0=ao+am+do+dm2(do+dm ) . thus , we see that direct and maternal effects have symmetrical effects on population mean fitness ( i.e. , their contributions are weighted equally in eq . 4 ) ( nordskog and hassan 1971 ) , and hence symmetrically affect the shape of the mean fitness surface . however , although they have symmetrical effects on mean fitness , they do not contribute symmetrically to evolutionary changes in allele frequencies ( illustrated by p1 , where p2=p1 ) : ( 6)p1=p1p2ao+12am+(p2p1)do+12dmw. the difference in the weighting of direct and maternal effects in equations ( 5 ) and ( 6 ) reflects the differential influence on the offspring genotypephenotype relationship ( see eq . , populations may not evolve to the peak on the mean fitness surface when there are both direct and maternal effects because of the asymmetrical weighting of maternal and direct genetic effects in the equation for allele frequency change ( eq . 6 ) . thus , while the direct and maternal parameters , am and dm , are weighted equally in the mean fitness surface ( eq . 4 ) , maternal effects are weighted by a factor of in the equation for evolutionary change ( eq . 6 ) because they are an indirect genetic effect ( so the weighting of here reflects the coefficient of relatedness between mothers and their offspring ) . as a result , the realized peak on the adaptive landscape ( corresponding to the evolutionary equilibrium ) occurs where the change in allele frequencies ( eq . 6 ) is zero ( not counting the trivial equilibria where p 1 = 1 or 0 ) : ( 7)p^1=2ao+am+2do+dm4do+2 dm in order to reconcile the fact that the dynamics of evolutionary change ( eq . 6 ) and location of equilibria are not reflected in the shape of the mean fitness surface ( eq . 4 ) we define the realized adaptive landscape ( i.e. , the equation that governs how a population will evolve in terms of allele frequencies ) , wr , as a fitness surface with direct and maternal effects weighted by their contribution to the genotypephenotype relationship : ( 8)wr=1+(p1p2)(ao+12am)+2p1p2(do+12 dm ) . the partial derivative of equation ( 8) with respect to p 1 is zero at the same equilibrium given by eq . phenotype relationship , direct effects ( ao and do ) are twice as important in a randomly mating population as maternal effects ( am and dm ) in determining the evolutionary dynamics and ultimate evolutionary equilibrium for a locus . in the classic quantitative genetic model of direct effects , the phenotype or fitness is a fixed property of the genotype independent of allele frequencies . with maternal effects , the expected phenotype of an offspring of a given genotype depends on the probability that it was produced by each of the different possible maternal genotypes ( table 2 ; see wade 1978 ) . this frequency dependence is apparent from the expected ( average ) offspring phenotypes given in table 1 , where the maternal effect contributions are all weighted by allele frequencies . to understand how this frequencydependent genotypephenotype relationship affects evolutionary dynamics , we can examine the realized additive genotypic value , ar ( o ) of the a locus , which ultimately determines how selection on offspring phenotypes drives evolution of maternal effects . using the classic definition of the additive genotypic value as half the difference between the phenotypes of the offspring homozygotes ( calculated as the mean of the a 1 a 1 minus the mean of the a 2 a 2 offspring ) , this is the value we could calculate if we simply examined the difference between the average phenotypes of the two offspring homozygotes , ignoring whether the difference arose as a consequence of a direct or a maternal effect ) . equation ( 9 ) demonstrates that half of the additive maternal effect ( am ) appears like an offspring direct effect because it makes the two homozygous offspring genotypes phenotypically distinct irrespective of allele frequencies ( wolf and cheverud 2012 ) . we also see that the dominance maternal effect ( dm ) weighted by ( p 2 p 1 ) contributes to the realized additive effect in offspring genotypes . most importantly , we see that , when the a 1 allele is more common that the a 2 allele , then the weighting term , ( p 2 p 1 ) , is negative , whereas when the a 1 allele is less common that the a 2 allele , the weighting is positive , and consequently the contribution of the dominance maternal effect to the additive genotypic value changes sign depending on which allele is more common . this phenomenon means that a maternal effect showing positive dominance ( dm > 0 ) , which might arise from overdominance for the maternal effect , would lead to negative frequency dependence wherein the rarer allele will appear to have a positive effect . in contrast , a maternal effect showing negative dominance ( dm < 0 ) , which might arise from underdominance for the maternal effect , would lead to positive frequency dependence . under random mating , the correlation between maternal and offspring genotypes , rmo , is onehalf , that is it equals the coefficient of relatedness ( i.e. , the correlation between alleles present in mothers and their offspring , not between their phenotypes ) . this correlation governs the contribution of maternal effects to the evolution of allele frequencies ( see eqs . 6 , 7 , 8 , 9 ) because they evolve through kin selection ( cheverud 1984 ) . therefore , inbreeding modifies the evolution of maternal effects because it alters the correlation between maternal and offspring genotypes . with inbreeding of degree f ( which corresponds to the reduction in the frequency of heterozygotes from that expected under random mating ) , the correlation between maternal and offspring genotypes is increased from to ( 1+f)/2 ( cf . harris 1964 ) . assuming that a population reaches an equilibrium level of inbreeding defined by f ( i.e. , where f is the same in parents and their offspring ) ( following wright 1969 ; wade 2000 ) , the expected phenotypes of each of the different maternaloffspring genotype combinations remain the same as in the random mating case ( i.e. , follows table 1 ) , but the frequencies of the maternaloffspring genotype combinations differ from the random mating case ( table 2 ) , and consequently , the expected phenotypes of each offspring genotype differ ( see table s1 in the supplementary material ) . inbreeding has differential influences on the contribution of additive versus dominance effects to components of variation because it resorts variation from heterozygote into homozygote classes , increasing the contribution of additive effects and diminishing those of dominance ( crow and kimura 1970 ) . we see this in our model where the contribution of additive effects to the genetic variance ( either direct or maternal effect ) is increased by a factor of ( 1 + f ) while the contribution of dominance effects is decreased by a factor of ( 1 f)/(1 + f ) ( cf . in addition to shifting the relative heterozygotehomozygote frequencies , inbreeding also changes the relationship between direct and maternal effects , reflected in the directmaternal genetic covariance ( where , as with eq . 1 , this covariance reflects the relationship between the direct effect of the individual 's own genotype and the maternal effect they experience from their mother 's genotype ) : ( 10 ) cov mo(f)=p1p2ao(1+f)+do(p2p1)(1f)am(1+f)+dm(p2p1)(1f ) . if there are only additive effects ( i.e. , do = dm = 0 ) , then the directmaternal covariance is increased by a factor of ( 1 + f ) , whereas , if there are only dominance effects , it is diminished by a factor of ( 1 f ) . although inbreeding has equivalent influences on direct and maternal effect variation ( table 3 ) , they make differential contributions to the additive genetic variance among offspring genotypes , which ultimately determines their contribution to heritable variation in and response to selection on offspring phenotypes : ( 11)va=2p1p2ao(1+f)+12am(1+f)2+(p2p1)(1f)do+12dm(1+f)2(1+f)=va(o)f+1+f24va(m)f+2 cov mo(f)=va(o)f+rmo2va(m)f+2 cov mo(f ) . it is clear from equation ( 11 ) that , when f = 1 ( a fully inbred population ) , direct and maternal effects both make the same relative contribution to the offspring additive genetic variance . therefore , although additive direct effects contribute twice as much as additive maternal effects in outbreeding populations , with increasing inbreeding , the difference diminishes to the point where the two make equivalent relative contributions . from elementary considerations , inbreeding must increase the amongfamily genetic variance and diminish the withinfamily genetic variance ( dickerson 1947 ) . with inbreeding , the variance among families of fullsiblings depends on the exact mating scheme , so we consider families of half siblings sharing the same mother . with inbreeding the amongmaternalhalfsib family variance is ( 12)v among = v maternal ( f)+2 cov mo ( f)+(1+f)24va(o)f = v maternal ( f)+2 cov mo ( f)+r om 2va(o)f , which demonstrates that inbreeding converts additive offspring variation to an amongfamily component of variation . as a result , in a fully inbred population ( f = 1 ) , both direct and maternal effects are exclusively amongfamily components of variation . the withinfamily variance is simply : v within = vd(o)f+(1r om 2)va(o)f . inbreeding also alters the evolutionary dynamics , affecting mean fitness through the decline in the frequency of heterozygotes ( and hence only affects the contribution of dominance to mean fitness ) : ( 13)w=+(p1p2)(ao+am)+2p1p2(do+dm)(1f ) inbreeding also influences the allele frequency dynamics in response to selection ( see wright 1969 ) : ( 14)p1=p1p2(1+f)ao+12am(1+f)+(p2p1)(1f)do+12dm(1+f)w. inbreeding changes the evolutionary dynamic by increasing the contribution of additive direct effects by a factor ( 1 + f ) ( cf . harris 1964 ; weir and cockerham 1977 ) and increasing that of the additive maternal effects by a factor of ( 1 + f ) . the contribution of direct dominance effects is decreased by a factor of ( 1 f ) , while dominance maternal effects are reduced by ( 1 f ) , which is smaller . with inbreeding , the allele frequency equilibria differ from those expected under random mating ( eq . first , inbreeding increases the correlation between the maternal and offspring genotypes ( rmo ) . second , inbreeding alters the relative contribution of additive effects to gene frequency change , but not their relative contribution to mean fitness . consequently , the adaptive landscape that determines the evolutionary equilibrium is one on which additive effects are weighted by a factor of ( 1 + f ) , giving the realized adaptive landscape : ( 15)wr=+(p1p2)(ao+rmoam)(1+f)+2p1p2(do+rmodm)(1f ) . the derivative of the realized adaptive landscape in equation ( 15 ) is zero under the same conditions that the change in allele frequency ( eq . 14 ) is zero ( not counting the trivial equilibria where p 1 = 1 or 0 ) . hence , the realized adaptive landscape predicts the evolutionary equilibrium while the mean fitness surface does not . this equilibrium occurs when : ( 16)p^1=ao+12am(1+f)(1+f)+do+12dm(1+f)(1f)(1f)2do+dm(1+f),which differs from that expected under random mating ( cf . the components of genetic variance resulting from direct effects and maternal effects , in the absence of the other , are given in table 3 . these expressions are equivalent to the classic expressions of the quantitative genetics literature ( falconer and mackay 1996 ) and are presented here for comparison . using the phenotypes in table 1 and the frequencies in table 2 we can derive the additive genetic covariance ( owing to pleiotropy ) between the direct effect of an individual 's own genes and the maternal effect it experiences arising from its mother 's genes ( i.e. , the covariance between direct and indirect genetic effects on the offspring 's phenotype ) ( willham 1963 ; riska et al . 1985 ; kirkpatrick and lande 1989 ; wolf and brodie iii 1998 ) , ( 1 ) cov mo = p1p2ao+do(p2p1)am+dm(p2p1 ) . patterns of direct and maternal effect variation in randomly mating and inbreeding populations ( with the degree of inbreeding given by f ) in each case , the variation associated with direct or maternal effects is defined in the absence of the other type of effect , so that the confounding of the effects does not contribute to the pattern of variation ( see the main text for the case where both occur simultaneously ) . variation under both random mating and inbreeding is decomposed in additive ( v additive ) and dominance ( v dominance ) genetic variation , where the total is simply the sum of these components . equation ( 1 ) also represents half of the additive genetic covariance between direct and maternal effects of the locus at the individual level ( i.e. , the additive genetic relationship between the influence that individuals genes have on their own phenotype and the influence of their genes on the phenotype of their offspring is 2covmo ) ( riska et al . it is important to keep in mind that the covmo is the covariance between effects ( direct and maternal ) on the phenotypes of an individual , not a measure of the maternaloffspring covariance ( i.e. , it is not a measure of the resemblance of mothers and offspring ) . variance component models of maternal effects have shown that this covariance plays an important role in determining how maternal effects contribute to the offspring genotypephenotype relationship and , thereby , to patterns of offspring phenotypic variation ( cf . the parameter gmo in kirkpatrick and lande and cov(ao , am ) in cheverud ) . maternal effects contribute to the offspring genotype phenotype relationship because offspring experience a maternal effect arising from their mother 's genome while also inheriting half their genes from their mother . with both direct and maternal effects , the variance among unordered ( vg ) offspring genotypes ( i.e. , combining the a 1 a 2 and a 2 a 1 heterozygotes into a single heterozygote class ) equals : ( 2)vg=2p1p2(ao+12am)+(p2p1)(do+12dm)2 + 2p1p2do2=[va(o)+14va(m)+2 cov mo]+vd(o)=va+vd . from equation ( 2 ) we see that the variation among offspring genotypes , vg , includes the variance arising from additive ( va ( o ) ) and dominance direct effects ( vd ( o ) ) , as well as one fourth of the additive genetic maternaleffect variance ( va ( m ) ) , and the additive genetic covariance between direct and maternal effects , which is twice the directmaternal genetic covariance ( covmo ) . the contribution of a single locus to the total genetic variance ( eq . 2 ) can be partitioned into additive and dominance components of genetic variation ( fisher 1918 ; falconer and mackay 1996 ) . with maternal effects , the additive genetic variance among offspring genotypes contains a component contributed by maternal effects and the directmaternal genetic covariance ( covmo ) ( dickerson 1947 ) . in equation ( 2 ) , the total additive genetic variance appears as the first term in brackets , where va = va(o)+14va(m)+2 cov mo , while the dominance genetic variance is the remainder or simply the direct dominance variance ( vd = vd ( o ) ) . this result demonstrates that , in addition to the contribution of direct effects ( va ( o ) ) to the additive genetic variance , both additive maternal effects and the additive maternaloffspring covariance ( twice the directmaternal genetic covariance , eq . a trait can have heritable variation ( i.e. , va > 0 ) even when the locus does not directly affect the expression of the trait ( i.e. , va ( o ) = 0 ) because maternal effects can contribute a component of heritable variation . likewise , the trait can be affected by both direct and maternal genetic effects ( i.e. , va ( o ) > 0 and va ( m ) > 0 ) , but have no heritable ( additive genetic ) variation overall because these two effects oppose each other ( i.e. , show a negative genetic covariance ) and therefore cancel each other out ( which occurs when cov mo=12[va(o)+14va(m ) ] ) ( see also dickerson 1947 for a discussion of trait heritability ) . interestingly , equation ( 2 ) also demonstrates that maternal effects contribute only to additive variation but not to dominance variation among offspring genotypes . because the two types of homozygous mothers ( a 1 a 1 and a 2 a 2 ) can each produce only one of the two types of reciprocal heterozygotes ( a 1 a 2 and a 2 a 1 , respectively , with the maternally inherited allele appearing first ; see table 1 ) , the phenotypes of the reciprocal heterozygotes will differ when there are maternal effects ( hager et al . maternal genetic effects contribute a component of variation between the reciprocal heterozygotes that is equal to 14va(m ) . because this variation is between the heterozygote classes that are genetically identical , but differ in the parent of origin of their alleles , it appears as a type of parentoforigin dependent variation , analogous to the imprinting variance ( spencer 2002 ) . although maternal genetic effects contribute to the variance among offspring genotypes , they also contribute variation that is not associated with the offspring genotype ( cf . for example , consider an idealized scenario where a maternal effect is caused by a single locus in a population of families of fullsiblings and accounts for all variation in some trait all offspring in the same family experience the same maternal effect because they share the same mother , and so they all have the same phenotype . however , offspring with the same phenotype owing to maternal effects may have different genotypes at the maternal effect locus because there is mendelian segregation variance within families . as a result , the offspring genotype at the maternal effect locus can not fully account for variation in offspring phenotype , despite the fact that the phenotype was determined by that locus albeit in the mother ( i.e. , through a maternal effect ) . therefore , while a maternal effect can be wholly genetically determined and fully account for offspring trait variation , when we measure variation among offspring , their genotype at the maternal effect locus only accounts for a component of that trait variation . the rest of the phenotypic variation contributed by maternal genetic effects is , therefore , uncorrelated to offspring genotype , and consequently , from the perspective of the offspring a component of phenotypic variation arising from maternal genetic effects appears to be a random environmental source of variation . this is not meant to imply that maternal genetic effects are environmental variation in the sense of being caused by the ecological environment , but rather , it follows from the standard partitioning perspective in quantitative genetics in which variation that is not explained by an individual 's genotype ( i.e. , variation that is random with respect to genotype ) is lumped together in the environmental variance . as a result , even when all phenotypic variation arises from genetic influences ( i.e. , from direct or maternal genetic effects ) , there can still be a component of random environmental variation among offspring genotypes ( i.e. , phenotypic variation among offspring that is not associated with their genotype ) corresponding to : ( 3)ve = p1p2am+dm(p2p1)2 + 2p1p2dm2=12va(m)+vd(m ) . equation ( 3 ) illustrates that half of the additive genetic maternaleffect variance and , all of the dominance maternaleffect variation appear as environmental components of variation from the perspective of the offspring genotype phenotype relationship ( i.e. , these maternal genetic effects contribute variation that appears within , not among , classes of offspring genotypes , and hence is conceptually the same as other sources of environmental variation ) . this result is implied in most models of maternal effects ( e.g. , willham 1963 ; kirkpatrick and lande 1989 ) , where the contribution of maternal effects to patterns of variation and response to selection in offspring are typically weighted by a factor of , but these earlier models considered only the contribution of additive maternal effects and not maternal dominance effects that predominate in ve . because maternal effects are attributed to the genotype of the mother , they contribute a component of variation among maternal families ( i.e. , among the groups of offspring produced by the different types of mothers ) ( dickerson 1947 ) . therefore , the entire maternal effect variance ( v maternal ) , shown in table 3 , appears as an amongmaternalfamily component of variation , while the contribution of direct effects to among family variation depends on the mating structure ( e.g. , whether offspring are fullsiblings or halfsiblings etc . ) . to understand the evolutionary consequences of maternal genetic effects for selection on offspring , we assume that the genetic parameters , ao , do , am , and dm , correspond to effects on offspring fitness . as above , we assume that selection stemming from these fitness differences is sufficiently weak that it does not produce significant deviations from the hardy weinberg expectations . ( see supplementary material , where we show that the deviations from h w proportions are generally o(s ) , where s represents the strength of selection ) the mean fitness of the population equals : ( 4)w=+(p1p2)(ao+am)+2p1p2(do+dm),where is the baseline ( expected ) fitness value that is not associated with variation at the a locus . this equation for population mean fitness is often described as the adaptive landscape ( wright 1932 ; see also ; svensson and calsbeek 2012 ) ; it represents the relationship between allele frequencies and expected fitness . in standard theory , .the fitness of individuals is affected by their own trait values , but not by the trait values of other individuals in the population ( arnold 2003 , p. 368 ) . that assumption is explicitly violated here where genes in the maternal genome affect the offspring trait value and fitness . regardless of whether this assumption is met , peaks on the adaptive landscape occur where the partial derivative of mean fitness ( w ) with respect to the frequency of either of the alleles is zero ( e.g. , when w/wp1p1=0 ) . taking the partial derivative of mean fitness in equation ( 3 ) with respect to p 1 and setting it equal to zero yields : ( 5)p1wp1=0=ao+am+do+dm2(do+dm ) . thus , we see that direct and maternal effects have symmetrical effects on population mean fitness ( i.e. , their contributions are weighted equally in eq . 4 ) ( nordskog and hassan 1971 ) , and hence symmetrically affect the shape of the mean fitness surface . however , although they have symmetrical effects on mean fitness , they do not contribute symmetrically to evolutionary changes in allele frequencies ( illustrated by p1 , where p2=p1 ) : ( 6)p1=p1p2ao+12am+(p2p1)do+12dmw. the difference in the weighting of direct and maternal effects in equations ( 5 ) and ( 6 ) reflects the differential influence on the offspring genotypephenotype relationship ( see eq . 2 ) . consequently , populations may not evolve to the peak on the mean fitness surface when there are both direct and maternal effects because of the asymmetrical weighting of maternal and direct genetic effects in the equation for allele frequency change ( eq . thus , while the direct and maternal parameters , am and dm , are weighted equally in the mean fitness surface ( eq . 4 ) , maternal effects are weighted by a factor of in the equation for evolutionary change ( eq . 6 ) because they are an indirect genetic effect ( so the weighting of here reflects the coefficient of relatedness between mothers and their offspring ) . as a result , the realized peak on the adaptive landscape ( corresponding to the evolutionary equilibrium ) occurs where the change in allele frequencies ( eq . 6 ) is zero ( not counting the trivial equilibria where p 1 = 1 or 0 ) : ( 7)p^1=2ao+am+2do+dm4do+2 dm in order to reconcile the fact that the dynamics of evolutionary change ( eq . 6 ) and location of equilibria are not reflected in the shape of the mean fitness surface ( eq . 4 ) we define the realized adaptive landscape ( i.e. , the equation that governs how a population will evolve in terms of allele frequencies ) , wr , as a fitness surface with direct and maternal effects weighted by their contribution to the genotypephenotype relationship : ( 8)wr=1+(p1p2)(ao+12am)+2p1p2(do+12 dm ) . the partial derivative of equation ( 8) with respect to p 1 is zero at the same equilibrium given by eq . equation ( 8) demonstrates that , because of their differential contributions to the genotype phenotype relationship , direct effects ( ao and do ) are twice as important in a randomly mating population as maternal effects ( am and dm ) in determining the evolutionary dynamics and ultimate evolutionary equilibrium for a locus . in the classic quantitative genetic model of direct effects , the phenotype or fitness is a fixed property of the genotype independent of allele frequencies . with maternal effects , the expected phenotype of an offspring of a given genotype depends on the probability that it was produced by each of the different possible maternal genotypes ( table 2 ; see wade 1978 ) . this frequency dependence is apparent from the expected ( average ) offspring phenotypes given in table 1 , where the maternal effect contributions are all weighted by allele frequencies . to understand how this frequencydependent genotypephenotype relationship affects evolutionary dynamics , we can examine the realized additive genotypic value , ar ( o ) of the a locus , which ultimately determines how selection on offspring phenotypes drives evolution of maternal effects . using the classic definition of the additive genotypic value as half the difference between the phenotypes of the offspring homozygotes ( calculated as the mean of the a 1 a 1 minus the mean of the a 2 a 2 offspring ) , this is the value we could calculate if we simply examined the difference between the average phenotypes of the two offspring homozygotes , ignoring whether the difference arose as a consequence of a direct or a maternal effect ) . equation ( 9 ) demonstrates that half of the additive maternal effect ( am ) appears like an offspring direct effect because it makes the two homozygous offspring genotypes phenotypically distinct irrespective of allele frequencies ( wolf and cheverud 2012 ) . we also see that the dominance maternal effect ( dm ) weighted by ( p 2 p 1 ) contributes to the realized additive effect in offspring genotypes . most importantly , we see that , when the a 1 allele is more common that the a 2 allele , then the weighting term , ( p 2 p 1 ) , is negative , whereas when the a 1 allele is less common that the a 2 allele , the weighting is positive , and consequently the contribution of the dominance maternal effect to the additive genotypic value changes sign depending on which allele is more common . this phenomenon means that a maternal effect showing positive dominance ( dm > 0 ) , which might arise from overdominance for the maternal effect , would lead to negative frequency dependence wherein the rarer allele will appear to have a positive effect . in contrast , a maternal effect showing negative dominance ( dm < 0 ) , which might arise from underdominance for the maternal effect , would lead to positive frequency dependence . under random mating , the correlation between maternal and offspring genotypes , rmo , is onehalf , that is it equals the coefficient of relatedness ( i.e. , the correlation between alleles present in mothers and their offspring , not between their phenotypes ) . this correlation governs the contribution of maternal effects to the evolution of allele frequencies ( see eqs . 6 , 7 , 8 , 9 ) because they evolve through kin selection ( cheverud 1984 ) . therefore , inbreeding modifies the evolution of maternal effects because it alters the correlation between maternal and offspring genotypes . with inbreeding of degree f ( which corresponds to the reduction in the frequency of heterozygotes from that expected under random mating ) , the correlation between maternal and offspring genotypes is increased from to ( 1+f)/2 ( cf . harris 1964 ) . assuming that a population reaches an equilibrium level of inbreeding defined by f ( i.e. , where f is the same in parents and their offspring ) ( following wright 1969 ; wade 2000 ) , the expected phenotypes of each of the different maternaloffspring genotype combinations remain the same as in the random mating case ( i.e. , follows table 1 ) , but the frequencies of the maternaloffspring genotype combinations differ from the random mating case ( table 2 ) , and consequently , the expected phenotypes of each offspring genotype differ ( see table s1 in the supplementary material ) . inbreeding has differential influences on the contribution of additive versus dominance effects to components of variation because it resorts variation from heterozygote into homozygote classes , increasing the contribution of additive effects and diminishing those of dominance ( crow and kimura 1970 ) . we see this in our model where the contribution of additive effects to the genetic variance ( either direct or maternal effect ) is increased by a factor of ( 1 + f ) while the contribution of dominance effects is decreased by a factor of ( 1 f)/(1 + f ) ( cf . in addition to shifting the relative heterozygotehomozygote frequencies , inbreeding also changes the relationship between direct and maternal effects , reflected in the directmaternal genetic covariance ( where , as with eq . 1 , this covariance reflects the relationship between the direct effect of the individual 's own genotype and the maternal effect they experience from their mother 's genotype ) : ( 10 ) cov mo(f)=p1p2ao(1+f)+do(p2p1)(1f)am(1+f)+dm(p2p1)(1f ) . if there are only additive effects ( i.e. , do = dm = 0 ) , then the directmaternal covariance is increased by a factor of ( 1 + f ) , whereas , if there are only dominance effects , it is diminished by a factor of ( 1 f ) . although inbreeding has equivalent influences on direct and maternal effect variation ( table 3 ) , they make differential contributions to the additive genetic variance among offspring genotypes , which ultimately determines their contribution to heritable variation in and response to selection on offspring phenotypes : ( 11)va=2p1p2ao(1+f)+12am(1+f)2+(p2p1)(1f)do+12dm(1+f)2(1+f)=va(o)f+1+f24va(m)f+2 cov mo(f)=va(o)f+rmo2va(m)f+2 cov mo(f ) . it is clear from equation ( 11 ) that , when f = 1 ( a fully inbred population ) , direct and maternal effects both make the same relative contribution to the offspring additive genetic variance . therefore , although additive direct effects contribute twice as much as additive maternal effects in outbreeding populations , with increasing inbreeding , the difference diminishes to the point where the two make equivalent relative contributions . from elementary considerations , inbreeding must increase the amongfamily genetic variance and diminish the withinfamily genetic variance ( dickerson 1947 ) . with inbreeding , the variance among families of fullsiblings depends on the exact mating scheme , so we consider families of half siblings sharing the same mother . with inbreeding the amongmaternalhalfsib family variance is ( 12)v among = v maternal ( f)+2 cov mo ( f)+(1+f)24va(o)f = v maternal ( f)+2 cov mo ( f)+r om 2va(o)f , which demonstrates that inbreeding converts additive offspring variation to an amongfamily component of variation . as a result , in a fully inbred population ( f = 1 ) , both direct and maternal effects are exclusively amongfamily components of variation . inbreeding also alters the evolutionary dynamics , affecting mean fitness through the decline in the frequency of heterozygotes ( and hence only affects the contribution of dominance to mean fitness ) : ( 13)w=+(p1p2)(ao+am)+2p1p2(do+dm)(1f ) inbreeding also influences the allele frequency dynamics in response to selection ( see wright 1969 ) : ( 14)p1=p1p2(1+f)ao+12am(1+f)+(p2p1)(1f)do+12dm(1+f)w. inbreeding changes the evolutionary dynamic by increasing the contribution of additive direct effects by a factor ( 1 + f ) ( cf . harris 1964 ; weir and cockerham 1977 ) and increasing that of the additive maternal effects by a factor of ( 1 + f ) . the contribution of direct dominance effects is decreased by a factor of ( 1 f ) , while dominance maternal effects are reduced by ( 1 f ) , which is smaller . with inbreeding , the allele frequency equilibria differ from those expected under random mating ( eq . first , inbreeding increases the correlation between the maternal and offspring genotypes ( rmo ) . second , inbreeding alters the relative contribution of additive effects to gene frequency change , but not their relative contribution to mean fitness . consequently , the adaptive landscape that determines the evolutionary equilibrium is one on which additive effects are weighted by a factor of ( 1 + f ) , giving the realized adaptive landscape : ( 15)wr=+(p1p2)(ao+rmoam)(1+f)+2p1p2(do+rmodm)(1f ) . the derivative of the realized adaptive landscape in equation ( 15 ) is zero under the same conditions that the change in allele frequency ( eq . 14 ) is zero ( not counting the trivial equilibria where p 1 = 1 or 0 ) . hence , the realized adaptive landscape predicts the evolutionary equilibrium while the mean fitness surface does not . this equilibrium occurs when : ( 16)p^1=ao+12am(1+f)(1+f)+do+12dm(1+f)(1f)(1f)2do+dm(1+f),which differs from that expected under random mating ( cf . the quantitative genetics framework built on variance component models has demonstrated that maternal effects contribute to evolutionary change through kin selection , because the response to selection on maternal effects is proportional to the relatedness between mother and offspring ( falconer 1965 ; willham 1972 ; cheverud 1984 , 1985 ; lynch 1987 ; kirkpatrick and lande 1989 ) . here , we use a singlelocus model to link these results from quantitative genetics to population genetic expressions for allele frequency change . our approach allows us to understand how maternal genetic effects influence the offspring genotypephenotype relationship and thereby influence evolutionary dynamics of maternal effects resulting from selection on offspring phenotypes ( i.e. , resulting from kin selection ) . by doing so we identify important results that do not appear in the classic quantitative genetic treatments of maternal effects . maternal genetic effects are a component of phenotypic variation that covaries with the genotype of the offspring due to the motheroffspring relatedness , a covariance that is enhanced by inbreeding . this covariance allows maternal genetic effects to evolve when selection acts on offspring phenotypes and is the underlying reason why models of maternal effects evolution are fundamentally kin selection models ( cheverud 1984 ) . variance component models of maternal effects ( see kirkpatrick and lande 1989 ) have found that half of the additive genetic variation in maternal effects must appear as phenotypic variation among the different offspring genotypes . we too find that half of the additive genetic variance in maternal effects appears as variation among offspring . however , we show further that half of this variation ( i.e. , of the total additive genetic variation in maternal effects ) arises because of the differences between the reciprocal heterozygotes , which have mothers of different genotype and therefore experience different maternal effects . for this reason , half of the total variance contributed by maternal genetic effects to differences among offspring genotypes appears as an difference between reciprocal heterozygotes , a finding typically associated with genomic imprinting ( see also santure and spencer 2006 ; hager et al . 2008 ) . consequently , maternal genetic effects and genomic imprinting effects cause similar patterns of phenotypic variation in populations that could well be confounded for one another unless their independent contributions are recognized ( hager et al . in general , the contribution of additive and dominance maternal effects to the evolutionary response to selection on offspring phenotypes is similar to that of direct effects , but is weighted by a factor of in an outbred population ( eq . 5 ) . however , they contribute to gene frequency change by a fundamentally different process with respect to the offspring genotypephenotype relationship . 7 ) that occurs when alleles at the alocus are overdominant in their direct effects but have no additive effects . this is the classic case of a fitness peak at a frequency of 0.5 ( fig . , populations evolve to the peak ( at an allele frequency of 0.5 ) and remain there because offspring heterozygotes have the highest mean fitness ( fig . in contrast , consider a maternal effect showing the same pattern of overdominance but with no additive maternal effect . here , the relative shape of the mean fitness surface is the same as that for the direct effects only case , but the realized adaptive landscape is flatter ( fig . 1a ) because of the reduced strength of the genotypephenotype relationship for maternal effects compared to that of direct effects ( i.e. , maternal effects experience indirect selection , where selection on offspring results in selection on maternal effects in proportion to the relatedness of mothers and their offspring , and hence their contribution to evolutionary change is lower than that of direct effects ) ( wolf 2000 ) . 1b ) , which leads to greater sequence variation at the equilibrium between mutation and balancing selection , a theoretical prediction supported by patterns of sequence variation in genes with maternal effects ( wade 1998 ; barker et al . 2005 ; cruickshank and wade 2008 ) . however , the evolutionary process is fundamentally different because maternal effects introduce frequency dependence into the offspring genotypephenotype relationship ( cheverud and wolf 2009 ) . with maternal effects , offspring genotypes no longer have a fixed phenotypic ( fitness ) value as they do in the direct effects model . rather , the expected phenotype ( fitness ) of an offspring genotype depends on allele frequencies because , as allele frequencies change , so too does the probability that a particular offspring genotype was produced by a given maternal genotype . with overdominant maternal effects ( fig . 2 ) we see that at no allele frequency does the heterozygote class have the highest fitness ; one of the two homozygote classes always has the highest fitness ( except at the equilibrium , where all genotypes have equal fitness ) . this pattern of genotypic fitness is manifested as a negative frequencydependent additive effect that is ar(o)=12dm(p2p1 ) ( cf . therefore , although the structure of the dynamical equation for change in allele frequency ( eq . 6 ) when there is an overdominant maternal effect is the same as for a direct effect , the evolutionary process differs from the perspective of selection on the offspring . these figures illustrate a case where there is a direct and a maternal effect of the same size showing only dominance ( values are arbitrary , so the y axis is shown as unit free ) . ( a ) the red ( dashed ) line shows the surface of mean fitness , while the blue line ( solid ) shows the ( b ) the change in allele frequency for a locus showing a direct or maternal dominance effect across allele frequency space . with either type of effect the population evolves to an internal equilibrium at p 1 = 0.5 when there is allelic variation , but the direct effect ( red , dashed ) evolves to the equilibrium faster than the maternal effect ( blue , solid ) , when started at the same gene frequency . the offspring genotype phenotype relationship for a maternal effect showing only dominance . ( a ) the expected offspring phenotype ( fitness ) for the three unordered offspring genotypes as a function of the frequency of the a 1 allele . it is always the case with maternal effect dominance that the mean fitness of the offspring heterozygote is midway between the two homozygotes . the fitness values are on an arbitrary scale and are not labeled ( but are all positive ) . ( b ) the realized additive effect of the locus is shown as a function of the frequency of the a 1 allele . perhaps the most important consequence of the frequencydependent offspring genotypephenotype relationship created by maternal effects is that , at the allele frequency equilibrium , the genotypephenotype relationship can disappear ( eq . 9 ) ( dickerson 1947 ) . if a locus only has a maternal effect , and no direct effect , then the change in allele frequencies and the realized additive effect are both zero when p1=(am+dm)/(am+dm)2dm2 dm . hence , with maternal genetic effects , evolution proceeds to an allele frequency where the offspring genotypephenotype relationship disappears , and consequently a population stops evolving because the locus is effectively neutral ( wade 2000 ) . if the locus also shows an additive direct effect , then both the change in allele frequency and the realized additive effect will be zero when p1=(2ao+am+dm)/(2ao+am+dm)2dm2 dm . this means that the direct and maternal effects cancel one another out , so that the locus appears to have no effect on the phenotype at the equilibrium allele frequency when in reality it has contrasting maternal and direct effects ( e.g. , wade 2000 ) . when displaced from this equilibrium , the locus will appear to have an additive effect that favors one of the two alleles , depending on the side of the peak from which it is displaced ( i.e. , this is the manifestation of the negative frequency dependence discussed above ) . thus , from an empirical perspective , this implies that the additive effect will change temporally within populations as allele frequencies evolve , and spatially across populations that differ in allele frequencies either by drift or selection . furthermore , if a population resides at an equilibrium allele frequency , the locus may appear to have no effect on the phenotype , which could be in conflict with an observation that the locus might show a molecular signature consistent with selection favoring a polymorphism . because of the differential weighting of direct and maternal effects to the realized adaptive landscape , when a locus has both a direct and a maternal effect there can be cases where a population is unable to find the peak on the mean fitness surface because selection on direct effects overwhelms the contribution of maternal effects . for example , if there is both an additive direct effect and a dominance maternal effect then there is significant parameter space where a peak on the mean fitness surface exists , but that peak is not instead , the population evolves to fix the allele with the positive direct effect on fitness ( fig . the evolution at a pleiotropic locus , one with both a direct and a maternal effect , does not necessary evolve to maximize mean fitness . the genetic but nonheritable components of maternal effects ( i.e. , those not reflected in the offspring genotypephenotype relationship ) are unavailable to selection . evolution of a locus showing an additive direct effect and a dominance maternal effect that produce a peaked fitness surface . ( a ) the red ( dashed ) line shows the surface of mean fitness , where there is a peak at an allele frequency of 0.75 . ( b ) the change in allele frequencies at the a locus ( p 1 ) as a function of the frequency of the a 1 allele , demonstrating that the population evolves to fixation of the a 1 allele . we note , however , that changing the level of selection from the individual offspring phenotype to the fullsib family mean makes the mean fitness surface equivalent to the adaptive landscape . thus , the fitness peak seen in figure 3 , unattainable by individual selection , becomes attainable by amongfamily selection and maximizes mean fitness . these results show why there are situations in which selection on group means ( here acting at the family level , where selection is based on the mean of a family ) could lead to higher mean fitness than individual selection ( e.g. , dickerson 1947 ; griffing 1967 ) . inbreeding can play an important role in the evolution of maternal effects ( wade 2000 ) because it increases the correlation ( rmo ) between maternal and offspring genotypes ( i.e. , the correlation between alleles in the mother and her offspring ) . it increases the contribution of maternal effects to variation among offspring genotypes and , consequently , the evolutionary response to selection ( dickerson 1947 ) . inbreeding increases the contribution of additive maternal effects to the additive offspring genetic variance by a factor rmo2 ( eq . as f increases , the relative contributions to the offspring additive variance of direct offspring and additive maternal effects equalize ( eq . the contribution of additive maternal effects is weighted by a factor of ( 1 + f ) ( eq . 14 ) while the contribution of additive direct effects is weighted by a factor of ( 1 + f ) . thus , inbreeding makes maternal genetic effects more available for an evolutionary response to selection , with the potential to double their contribution to adaptation when a population is fully inbred ( see also wade 2000 ) . figure s1 . comparison of genotype frequencies after selection to the hardyweinberg expectation . . evolutionary trajectories at the a locus ( illustrated as the frequency of the a1 allele , p1 , through generations ) comparing the qhw approximation with the exact dynamics . evolutionary trajectories at the a locus ( illustrated as the frequency of the a1 allele , p1 , through generations ) for the single locus case and the two locus case for a series of arbitrary scenarios . the expected phenotypes of offspring as a function of the offspring genotype or maternal genotype .
maternal genetic effects ( mges ) , where genes expressed by mothers affect the phenotype of their offspring , are important sources of phenotypic diversity in a myriad of organisms . we use a singlelocus model to examine how mges contribute patterns of heritable and nonheritable variation and influence evolutionary dynamics in randomly mating and inbreeding populations . we elucidate the influence of mges by examining the offspring genotypephenotype relationship , which determines how mges affect evolutionary dynamics in response to selection on offspring phenotypes . this approach reveals important results that are not apparent from classic quantitative genetic treatments of mges . we show that additive and dominance mges make different contributions to evolutionary dynamics and patterns of variation , which are differentially affected by inbreeding . dominance mges make the offspring genotypephenotype relationship frequency dependent , resulting in the appearance of negative frequencydependent selection , while additive mges contribute a component of parentoforigin dependent variation . inbreeding amplifies the contribution of mges to the additive genetic variance and , therefore enhances their evolutionary response . considering evolutionary dynamics of allele frequency change on an adaptive landscape , we show that this landscape differs from the mean fitness surface , and therefore , under some condition , fitness peaks can exist but not be available to the evolving population .
bioactive surfaces consisting of patterned proteins in specific defined geometries are important for screening applications , sensing [ 15 ] , the study of cell - cell interactions [ 2 , 6 , 7 ] , and the creation of cellular networks [ 2 , 5 , 810 ] or cellular aggregates for tissue engineering applications [ 11 , 12 ] . a long sought after capability is the ability to fabricate patterned surfaces with cellular - like interfacial features ( e.g. , cell recognition , adhesion , and stimulatory ligands ) to enhance cell - substrate interactions . such biomimetic approaches require surface engineering with multiple chemical functionalities to facilitate attachment of a variety of proteins and to date , methodologies have been lacking in the robust production of arrays with multiple functionalities . although surfaces capable of binding proteins at high densities are commercially available , these slides are designed for protein microarray screening and , in turn , require method development if specific patterns are required . current molecular patterning techniques such as poly(dimethylsiloxane ) ( pdms ) molding [ 9 , 10 , 14 ] are harsh in their application , potentially compromising surface functionality . several groups have developed photo- and chemically - sensitive materials for protein patterning [ 5 , 7 , 1517 ] ; however , the techniques all require noncommercially available molecules and most have not yet been demonstrated to be capable of patterning multiple bioactive proteins [ 1517 ] . novel patterning approaches have also been developed , including microfluidic - directed patterning and dip - pen lithography ( dpl ) . despite their promise in a number of applications , serial techniques such as dpl are not currently suited for the creation of large patterns and arrays and microfluidic patterning places strict geometric limitations on patterns . here we present a novel , photolithographic - based approach to create surfaces consisting of arrays of functional patterned proteins that uses only commercially available materials , as opposed to previously proposed methods [ 7 , 1517 , 1921 ] . we demonstrate our approach with a biomimetic structure inspired by the immunological synapse , an immunologically complex structure that occurs after lymphocytes encounter antigen - presenting cells . the interfacial geometry of this structure is characterized by two concentric rings of proteins : an outer adhesion protein structure and an inner recognition ligand core . the spatial reorganization of molecules on the surface of immune system cells such as t cells is a hallmark of early t - cell responses to foreign invasion . following interaction with antigen - presenting cells ( apcs ) this spatial reorganization takes a specific form , termed an immunological synapse ( is ) , which facilitates the encoding of information dictating the magnitude of the immune response . pattern , which consists of regions termed supramolecular activation clusters ( smacs ) [ 2325 ] . the central smac ( csmac ) consists of interactions between t - cell receptors ( tcrs ) on the t - cell and peptide - loaded major histocompatibility complexes ( pmhcs ) on the apc . sensitivity is achieved because clustering promotes a high avidity interaction in the csmac [ 2325 ] . thus , creation of apc mimics on a surface would not only facilitate the study of t cell - apc signaling but may enable a recapitulation of sensitive sensing mechanisms employed by t cells in recognition of antigen [ 6 , 7 ] . recently , the application of a specially synthesized photoresist was demonstrated for the successful patterning of a surface with is - like domains . despite the utility of the approach , this technique is not applicable for the formation of specific and precise patterned two - dimensional is structures as observed in biological interactions . a cellular - repellant moiety such as poly(ethylene glycol ) ( peg ) can not be bound at the periphery of these stuructures , thus cells adhere across the entire substrate rather than specifically at the iss , compromising the utility of the approach for specific detection [ 26 , 27 ] . we demonstrate here a method capable of patterning functional antibodies and peg in any defined geometry using only commercially available products . we use this technique to create a patterned is with one antibody conjugated in the central region and another in the peripheral region of the is , surrounded by poly(ethylene glycol ) ( peg ) [ 26 , 27 ] . our method thus produces a surface with three chemical functionalities , created by two successive steps of traditional photolithographic patterning followed by functionalization with chemical cross - linkers . an attractive feature of this method is that subsequent conjugations to these groups with specific molecules after photoresist removal was performed entirely in aqueous buffers , thus protein functionality is not compromised . 16001 - 008 ) and were cut to 1 in pieces using a diamond scribe . photomasks were purchased from benchmark technologies and photo sciences , inc and transparency photomasks were purchased from cad art services . all photoprocessing steps were performed in a class 1000 cleanroom ( harvard center for nanoscale systems ) . the photoresist used for all processing was az 5214-e ( microchem ) , an inverting resist . glutaraldehyde , hydroxylamine , dimethyl sulfoxide ( dmso ) , phosphate buffered saline ( pbs ) , ethylenedinitrilotetraacetic acid ( edta ) , sodium cyanoborohydride , the fluorescein-5-isothiocyanate ( fitc ) conjugate of bovine serum albumin ( bsa - fitc ) , and mouse iga were purchased from sigma - alrich ; n - succinimidyl - s - acetylthioacetate ( satp ) , n-(6-(biotinamido)hexyl)-3-(2-pyridyldithio)-propionamide ( biotin - hpdp ) , sulfosuccinimidyl acetate ( nhs - acetate ) , n - hydroxysulfosuccinimide ( nhs ) , and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide ( edc ) were purchased from pierce biotechnology ; amine - terminated poly(ethylene glycol ) ( nh2-peg ; 10 kda ) and aldehyde - terminated peg ( cho - peg ; 10 kda ) were purchased from polysciences , inc ; fitc , alexafluor 568 hydrazide sodium salt ( alexafluor 568 ) , alexafluor 568 c5 maleimide ( alexafluor 568 maleimide ) , streptavidin , and atto565-biotin were purchased from invitrogen . liftoff processing was used to pattern metal alignment marks on the slides for subsequent photolithographic steps . amine - functionalized slides were cleaned with acetone and isopropanol ( baker chemical co. ) and dried with nitrogen . photoresist ( az 5214-e ) was spun on the slide at 3000 rpm using a headway spinner . the slide was then baked at 90c , exposed with the photomask using an ab - m maskaligner , baked at 110c , and finally flood exposed . the slide was then developed in mf319 ( microchem ) , washed with deionized water ( di ; 18 m ) , and blown dry with nitrogen . the slides were then loaded into a sharon systems electron - beam evaporator , where a 100 nm titanium ( 99.9% , kurt j. lesker co. ) deposition was performed . after unloading , the slide was sonicated in acetone to remove the remaining photoresist , leaving only the metal alignment marks . subsequent patterning steps followed the same procedure ( without metal evaporation ) with the exceptions that the photoresist was spun at 5000 rpm and that acetone was used to remove the photoresist without sonication . the slide containing the first layer of photoresist was treated for 1 hour at room temperature ( rt ) with a 0.01 m solution of glutaraldehyde in 0.1 m sodium acetate buffer , ph 5.5 , with 1 mm sodium cyanoborohydride . sodium cyanoborohydride was required for reduction of the unstable imine ( c = n ) bond . for all conjugation steps , the slides were placed face - up at the bottom of a 100 ml beaker with ~10 ml solution ( enough to completely immerse the slide in the solution ) and the beaker was covered with parafilm and placed on a shaker table . after each conjugation , the slide was removed , rinsed with di , and blown dry with nitrogen ( note after protein conjugation steps the slides were rinsed with pbs and not allowed to dry . n - succinimidyl - s - acetylthiopropionate ( satp ; 2 mg ) was dissolved in 0.5 ml dmso , which was added to 9.5 ml pbs and the slide containing the second layer of photoresist was treated for 30 minutes at rt with this solution . after washing , the slide was treated with a solution of 0.5 m hydroxylamine and 25 mm edta in pbs , ph 7.4 , for 2 hours at rt to deprotect the sulfhydryl groups . slides were treated with a 1% ( w / v ) solution of nh2-peg in pbs , ph 7.4 , with 1 mm sodium cyanoborohydrate for 46 hours at rt . n-(6-(biotinamido)hexyl)-3-(2-pyridyldithio)-propionamide ( biotin - hpdp ; 1 mg ) was dissolved in 0.5 ml of dmso , which was added to 9.5 ml of a 1 mm solution of edta in pbs , ph 7.4 . we obtained more repeatable results when the biotin - hpdp conjugation followed that with nh2-peg . mouse igg , biotinylated - mouse iga , antimouse igg - fitc , and anti - lfa-1-fitc were used as received . antimouse - iga was dissolved to 1 mg / ml in pbs , ph 7.4 , alexafluor 568 hydrazide was added to achieve a final concentration of 0.1 mg / ml , and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride ( edc ) was added at 10 mg / ml . the reaction proceeded for 1 hour at rt with shaking and protected from light . a 50 ml amicon ultra ( millipore , cat . # ufc905024 ) centrifugal filter tube with a 50000 mw cutoff was used to remove unconjugated dye ( 4 30-minute spins at 3000 rpm at 4c ) and the resulting antimouse - iga - alexafluor568 was diluted to 1 mg / ml . the same procedure was used for alexafluor 568 conjugation to biotinylated - anti - cd3. conjugates were stored at 4c . mouse igg or anti - lfa-1-fitc was dissolved to 10 g / ml in pbs with 10 mg / ml edc and 5 mg / ml n - hydroxysulfosuccinimide ( sulfo - nhs ) and reacted with the slide for 1 hour at rt . washes with protein bound on the chip took place in pbs and the slides were not dried . acetylated streptavidin was used because we found this protein to minimize nonspecific binding on the peg surface ( as compared with pure streptavidin , avidin , and neutravidin ) . to prepare the acetylated streptavidin , 5 mg / ml ( sulfosuccinimidyl acetate ) nhs - acetate was added to 1 mg / ml streptavidin in pbs , ph 7.4 . the reaction proceeded for 1 hour at rt and the streptavidin conjugate was purified using a 50 ml amicon ultra centrifugal filter tube with a 10000 mw cutoff ( 4 30-minute spins at 3000 rpm at 4c ) . the slides were treated with 10 g / ml streptavidin - ac in pbs , ph 7.4 , for 1 hour at rt . biotinylated - mouse igg or biotinylated anti - cd3-alexafluor568 were dissolved to 50 g / ml in pbs and reacted with the slide for 1 hour at rt ( the latter was protected from light ) . when this reaction was completed , slides treated with anti - lfa-1-fitc and biotinylated - anti - cd3-alexafluor 568 were dried ( gently ) and viewed under a fluorescent microscope ( olympus ix81 , equipped with the carv - ii unit from bd biosciences ) . the low - intensity areas in the bottom of some images ( notably figure 3(d ) ) are due to the directional nature of the stream of air during this drying step . slides containing mouse igg and biotinylated - mouse iga were treated with a pbs , ph 7.4 , solution containing 50 g / ml antimouse - igg fitc and 50 g / ml antimouse - iga - alexafluor 568 for 1 hour at rt . in figure 1 ( step 1 ) , photoresist spun on amine - functionalized microscope slides was patterned and the exposed amine groups were converted to aldehydes with glutaraldehyde . subsequent removal of the photoresist left a slide with two functionalities , with the aldehydes defining areas between the iss . successful glutaraldehyde conjugation was first demonstrated using a transparency photomask consisting of an array of 25 25 m squares ( clear on a dark background ) , followed by gluaraldehyde treatment . aldehyde functionality was thereby conferred to all areas of the chip but these squares . the photoresist was subsequently removed and the slide was treated with aldehyde - reactive peg ( nh2-peg ) . after subsequent treatment with fluorescein-5-isothiocyanate ( fitc ) , a fluorescent amine - reactive probe , the slides were fluorescently imaged under a gfp filter ( figure 2(a ) ) . the square fluoresces due to the conjugation of fitc to the amine surface but the formation of an amide bond between the surface aldehyde and free amine of the nh2-peg prevents fitc binding in areas surrounding the square . in step 2 , a second photoresist layer was applied and patterned and the available amine groups were reacted with satp , resulting in the conversion of exposed amine groups to protected thiols . photoresist removal with acetone followed by thiol deacetylation with hydroxylamine thus resulted in a slide with three chemical functionalities , where the thiols defined the csmac and the remaining amines defined the psmac . in order to demonstrate successful satp conjugation , slides were photopatterned with a transparency mask consisting of an array of 25 25 m squares ( dark on a clear background ) followed by satp conjugation and subsequent deprotection . the photoresist was then removed and slides were treated with amine - reactive peg ( cho - peg ) . a sulfhydryl - reactive fluorescent probe ( alexafluor 568 maleimide ) was then conjugated to the slides and subsequent fluorescent imaging using a tritc filter showed that the high fluorescence intensity was confined to the squares , demonstrating that sulfhydryl groups are present in these areas ( figure 2(b ) ) . as shown in step 3 , in order to eliminate nonspecific adsorption of cells to nonsynaptic regions of the slide , nh2-peg ( 10 kda ) was conjugated to the exposed aldehydes . next , biotin - hpdp was conjugated to the thiols in the csmac region , thereby biontinylating this area and readying the slide for protein conjugation . biotin - hpdp conjugation was demonstrated by processing slides with a transparency mask containing an array of 25 25 m squares ( dark on a clear background ) , followed by satp conjugation and deprotection . after photoresist removal slides were treated with cho - peg , followed by biotin - hpdp . the slides were then treated with acetylated streptavidin ( streptavidin - ac ) , followed by treatment with atto565-biotin , a fluorescently conjugated biotin molecule . slides were fluorescently imaged under a tritc filter ( figure 2(c ) ) . as in figure 2(b ) , the high fluorescence intensity is confined to the square , demonstrating the successful conjugation of biotin - hpdp to the sulfhydryl groups , as well as subsequent streptavidin - ac and atto565-biotin binding . protein conjugation to slides using edc / sulfo - nhs coupling ( step 4a ) was demonstrated by processing slides with a transparency mask containing an array of 25 25 m squares ( dark on a clear background ) , followed by satp conjugation and deprotection . after photoresist removal , slides were treated with biotin - hpdp , as described above . bsa - fitc was then added to the chip with 10 mg / ml edc and 5 mg / ml sulfo - nhs . the slides were then treated first with streptavidin - ac and next with atto565-biotin . fluorescence imaging was performed with both gfp ( figure 2(d ) ) and tritc ( figure 2(e ) ) filters ( images are from the same array point ) . the high fluorescence intensity in the region surrounding the square in figure 2(d ) indicates that bsa - fitc binding was confined to this region , while the high fluorescence intensity in the square in figure 2(e ) shows that atto565-biotin binding was confined to this region . we next demonstrated the ability of this approach to pattern the surface with functional antibodies ( step 4a ) . we first conjugated mouse - immunoglobulin g ( igg ) to the exposed amine groups through standard edc / sulfo - nhs chemistry . the slide was then treated with acetylated streptavidin and subsequently with biotinylated mouse - immunoglobulin a ( iga ) . unlike other patterning techniques [ 1517 ] , our approach does not require the presence of blocking agents during the final conjugation steps . the slide was next incubated with an fitc conjugate of antimouse - igg and an alexa fluor 568 conjugate of antimouse - iga , washed , and imaged . the fluorescent micrographs in figure 3 demonstrate the functionality of the conjugated antibodies as well as their segregation into different regions dictated by the surface functional groups . this also enables the creation of arrays of patterns with varying absolute and relative dimensions . this chemistry can be utilized to functionalize slides with physiologically relevant antibodies to mimic the is . for this purpose we chose antibodies to two ligands known to be sequestered in the is : an antibody to leukocyte function - associated antigen 1 ( anti - lfa-1 ) as the adhesion promoter for the psmac and an antibody to the subunit of cluster of differentiation 3 ( anti - cd3 ) , a well - established t - cell stimulus , for the csmac [ 7 , 25 ] . as shown in step 4b of figure 1 , antimouse - lfa-1 ( fitc conjugate ) was coupled to the free amines in the psmac region , followed by treatment of the slide with biotinylated antimouse - cd3 ( alexafluor 568 conjugate ) , which bound the streptavidin in the csmac ( figure 4 ) . we chose to use streptavidin as the linker chemistry in the csmac because biotinylated t - cell stimuli ( pmhcs and antibodies ) are readily available . the dimensions of the smac mimics shown in figure 4 are similar to those of t cells [ 2325 ] . the protein patterns were stable for > 2 months when slides were stored in pbs at 4c . the power of this technique is its simplicity of implementation and ability to create massive arrays in parallel of specifically - defined two - dimensional protein patterns without the need for blocking agents during conjugation steps , enabling cell patterning and the study of cellular interactions . although we focused on the formation of surface smac mimics , any geometry is easily realized much like integrated circuits by designing and using a specific photomask set . additionally , by combining this approach with that of microarray printing , arrays can be created in which each element contains a different functionality , enabling high - throughput screening . supporting information available . an alternative route to surface is functionalization is given in addition to two figures , one a schematic describing the method and a second showing fluorescent optical micrographs of representative iss patterned using the approach .
current efforts in surface functionalization have not produced a robust technique capable of creating specific two - dimensional microscale geometrical arrays composed of multiple proteins . such a capability is desirable for engineering substrates in sensing and cell patterning applications where at least two different protein functionalities in a specific configuration are required . here we introduce a new approach for the creation of arrays of microscale geometries . we demonstrate our approach with a biomimetic structure inspired by the immunological synapse , a cell - cell interfacial structure characterized by two concentric rings of proteins : an outer adhesion protein structure and an inner recognition ligand core . the power of the technique lies in its ability to pattern any protein in any defined geometry as well as to create arrays in parallel .
SECTION 1. SHORT TITLE. This Act may be cited as the ``Wholesale Motor Fuel Fairness and Competition Restoration Act''. SEC. 2. FINDINGS. The Congress finds that-- (1) both wholesale and retail motor fuel prices are the result of a number of complex factors, including those related to supply, refining, consumer demand, and oil company cost, pricing, and marketing practices; (2) certain cost, pricing, and marketing practices employed by the oil companies are unfair and anticompetitive, and contribute to the unjustified price of retail motor fuel charged the American consumer; (3) among the unfair and anticompetitive oil company practices are price zoning, redlining, discriminatory wholesale motor fuel pricing, and a complex system of cost allocation that hides the factors on which wholesale costs are based; (4) the oil companies' practice known as price zoning is one by which prices for motor fuel are set solely because of the retail station's geographic location unrelated to cost-of- business factors; (5) price zoning allows an oil company to artificially increase or depress retail motor fuel prices in order to secure an unfair market advantage against competitors; (6) the oil companies engage in a practice known as redlining, whereby a refiner refuses to sell motor fuel to distributors or particular geographic markets; (7) redlining allows an oil company to force concessions from a distributor and affords the company the opportunity to exert undue influence in a particular area or region; (8) the oil companies engage in a practice of discriminatory wholesale pricing of motor fuel based on the relationship of the purchaser to the oil company and the degree of competition they provide; (9) discriminatory pricing allows oil companies to charge different wholesale prices to company owned and operated retail stations, franchisees, and independent retailers though all may be situated in the same community and face the same competitive and operating factors; (10) the oil companies engage in a complex system of cost allocations by which they employ rebates, incentives, credits, and market enhancement allowances that hide the factors on which wholesale prices are based or published; (11) the complex system of cost allocation allows oil companies to post a ``wholesale price'' that is far different from the actual wholesale price that would be revealed if the cost factors were publicly identified and appropriately allocated; and (12) it is appropriate for the Federal Government to prohibit these unfair oil company cost, pricing, and marketing practices, to restore fair and competitive practices to the wholesale sale of motor fuel, and to allow American consumers to assess for themselves the factors that contribute to the price changes they pay at the retail pump. SEC. 3. PRICE DISCRIMINATION PROHIBITION. (a) Prohibition.-- (1) In general.--It shall be a violation of this Act for an owner or operator of a terminal facility to sell motor fuel from the terminal facility to any person at a price in excess of the price it charges any other person, including a distributor or retailer which it owns or with which it is affiliated. (2) Price determination.--For purposes of this subsection, the price an owner or operator of a terminal facility charges a distributor or retailer which it owns or with which it is affiliated shall be the price determined pursuant to the regulations issued under section 4(a). (3) Exception.--A sale shall not be in violation of this subsection if it is made pursuant to the terms of a franchise or sales contract entered into before the date of the enactment of this Act. (b) Civil Penalty.--The Federal Trade Commission may assess a civil penalty, not to exceed $1,000,000, for each violation described in subsection (a). (c) Criminal Penalty.--Whoever knowingly violates subsection (a) shall be fined under title 18, United States Code, or imprisoned not more than 5 years. (d) Effective Date.--This section shall take effect 6 months after the date of the enactment of this Act. SEC. 4. FULL DISCLOSURE. (a) Requirement.--The Federal Trade Commission, in consultation with the Secretary of Energy, shall issue regulations requiring full disclosure by refiners and distributors of their wholesale motor fuel pricing policies, with a separate listing of each component contributing to prices, including the cost of crude oil (with exploration, extraction, and transportation costs shown separately if the refiner or distributor is also the producer of the crude oil), refining, marketing, transportation, equipment, overhead, and profit, along with a description of any rebates, incentives, and market enhancement allowances. Such regulations shall establish procedures for determining the price an owner or operator of a terminal facility charges a distributor or retailer which it owns or with which it is affiliated. (b) Effective Date.--The regulations issued under subsection (a) shall take effect 6 months after the date of the enactment of this Act. (c) Public Dissemination.-- (1) Requirements.--Except as provided in paragraph (2), the Federal Trade Commission shall ensure that all information acquired pursuant to the regulations issued under subsection (a) is made available to the public as follows: (A) Such information may be disseminated to the public through the Energy Information Administration. (B) Such information shall be required by the Federal Trade Commission to be-- (i) conspicuously posted at all retail motor fuel facilities in a manner so as to be clearly available and understandable to retail consumers; and (ii) included in or with each invoice for the wholesale sale of motor fuel. (2) Exception.--The requirements of paragraph (1) shall not apply to trade secrets and commercial or financial information protected from disclosure under subsection (b)(4) of section 552 of title 5, United States Code (commonly referred to as the Freedom of Information Act). SEC. 5. DEFINITIONS. For purposes of this Act, any term defined in section 101 of the Petroleum Marketing Practices Act (15 U.S.C. 2801) shall have the meaning given the term in that Act.
Wholesale Motor Fuel Fairness and Competition Restoration Act - Declares that it shall be unlawful for an owner or operator to sell motor fuel from its terminal facility to any person in excess of the price it charges any other person, including a distributor or retailer which it owns or with which it is affiliated. Exempts from such prohibition certain franchises or sales contracts entered into before enactment of this Act.Establishes civil and criminal penalties for violations of this Act.Instructs the Federal Trade Commission to: (1) issue regulations requiring full disclosure by refiners and distributors of their wholesale motor fuel pricing policies, with a separate listing of each component contributing to prices, including the cost of crude oil, refining, marketing, transportation, equipment, overhead, and profit, along with a description of any rebates, incentives, and market enhancement allowances; and (2) ensure that all information acquired pursuant to such regulations is disseminated to the public.
gwne miejsce powstawania materiau zakrzepowo - zatorowego stanowi uszko lewego przedsionka ( left atrial appendage na przestrzeni lat rozwinito szereg chirurgicznych , przezskrnych i hybrydowych metod zamykania laa . ze wzgldu na specyfik tego obszaru terapie te wi si nadal jednak z szeregiem wyzwa i ogranicze . w pracy przedstawiono pierwsze polskie dowiadczenia z izolowanym cakowicie torakoskopowym zamkniciem laa z uyciem nowego sytemu opartego na mechanizmie klipsowania . czterech pacjentw ( 1 mczyzna ) w rednim wieku 74 ( 13 ) lat z przetrwaym , dugo trwajcym i utrwalonym migotaniem przedsionkw zostao zakwalifikowanych do cakowicie torakoskopowego zamknicia laa . u wszystkich pacjentw wystpoway liczne obcienia dodatkowe oraz nietolerancja lub niestabilny poziom antykoagulacji doustnej ( cha2ds2-vasc > 5 , has_bled > 3 ) . u jednego pacjenta z powodu masywnych zrostw w lewej opucnej niezbdne byo wykonanie minitorakotomii lewostronnej w czwartym midzyebrzu . u wszystkich pacjentw przebieg rdoperacyjny oraz zamknicie laa przebiegao bez powika , z potwierdzonym cakowitym wykluczeniem jego wiata . pierwsze polskie dowiadczenia z cakowicie torakoskopowym systemem do zamykania uszka lewego przedsionka wskazuj na wysok skuteczno oraz bezpieczestwo tej metody leczenia u pacjentw wysokiego ryzyka udaru mzgu . atrial fibrillation ( af ) is the most common clinically relevant arrhythmia , and it is strongly associated with stroke . the left atrial appendage ( laa ) is the most frequent source of thrombotic material leading to cerebrovascular events . oral anticoagulation remains the standard of care of patients with af . recent publications indicate that laa closure might not be inferior to oral anticoagulation in patients in whom it is not recommended . current guidelines of the european society of cardiology reflect this position , indicating that laa closure in this group of patients ( elevated cha2ds2-vasc and/or has - bled with contraindications for oral anticoagulation ) may be recommended [ 2 , 3 ] . in recent decades a number of surgical , percutaneous and hybrid approaches for laa occlusion have been described , revealing very different levels of success and showing a variety of challenges associated with this issue . we present the first polish experience with the new clipping system for totally thoracoscopic laa exclusion . the device for surgical totally thoracoscopic left atrial appendage occlusion atriclip pro laa exclusion system ( atriclip , atricure , dayton , oh , usa ) consists of an automatically closing clip placed in a deployment loop on a disposable holder with head articulation of 60 degrees side - to - side and up / down ( fig . the several novel features of the system in comparison to previous ones , such as its length , maneuverability and releasing system , enable it to be used in a totally thoracoscopic fashion . the atriclip pro has parallel titanium crossbars that equalize the force over the tissue trabeculations of the laa during deployment , ensuring a sealed line at the base of the laa orifice , as was confirmed in preclinical and clinical studies . atriclip pro laa exclusion system ( courtesy of atriclip , atricure , dayton , oh , usa ) four patients ( one man , three women ) at mean age of 74 ( 13 ) years with long - standing persistent and chronic atrial fibrillation were admitted to our department for totally thoracoscopic left atrial appendage ( laa ) exclusion in order to reduce the risk of stroke and complications of inadequate anticoagulation . all patients had significant comorbidities ( table i ) and a history of oral anticoagulation intolerance or a suboptimal / unstable level . the mean left ventricle ejection fraction was 48% ( 11% ) , and the mean left atrial diameter was 47 mm ( 2 mm ) . the minimal cha2ds2-vasc score was 5 and the has - bled score was over 3 , in one patient reaching 7 points ( table ii ) . all patients prior to the operation underwent transesophageal echocardiography ( tee ) to rule out thrombus in the laa . patient characteristics the patients were placed in the supine position and were intubated under general anesthesia with a double lumen intratracheal tube . one through the fourth intercostal space in the anterior axillary line ( for the endoscopic camera ) , and two through the third and sixth intercostal spaces at the midaxillary line into the left pleura ( working ports ) ( fig . pericardiectomy was performed parallel to the phrenic nerve to visualize the laa , beneath the nerve in 3 patients and above in one patient . stay sutures were placed on the lower edge of the pericardium for better access to the laa . if necessary one stay suture on the upper edge of the pericardium was added ( fig . the diameter of the base of the laa was measured with a dedicated selection guide ( fig . the atriclip pro was introduced through the incision in the sixth intercostal space enlarged to 2 - 3 cm . under tee control it was deployed at the base of the left atrial appendage with special care in order not to leave any residual stump ( fig . the possibility of repeated opening of the clip before the final deployment enabled correction of its position if the intraoperative echocardiography showed incomplete laa closure or an laa remnant . we performed minithoracotomy in the fourth left intercostal space laterally to the mammary line . by gentle dissection , the direct visualization of the laa was easily achieved . the skin - to - skin procedural time took on average 40 , minimum 20 minutes . thoracoscopic ports placement on the left side of the chest stay sutures and access to left atrial appendage measurement of the base of the left atrial appendage in order to choose the proper size of atriclip pro fully deployed atriclip pro intraoperative transesophageal echocardiographic monitoring . left atrial appendage ( a ) . atriclip pro at the base of left atrial appendage ( laa ) the perioperative period was uneventful . the two next patients were extubated directly after the procedure in the operating room . except for one patient with extreme coagulopathy due to three patients were discharged home on the second or third postoperative day in a good condition . one patient due to many extracardiac comorbidities required longer stay without any additional complications and was discharged in a good condition on the sixth postoperative day . during two months of follow - up we observed no bleeding events , no strokes , and no mortality . the recommendations for the laa exclusion have been widened over recent years , but still there are many questions to be answered . in previous decades cardiac surgery was the only source of knowledge in this area ; it revealed a number of challenges associated with this apparently easy task of closing or excluding a small appendage within the left atrium . in recent years a few percutaneous and hybrid technologies have been introduced , showing good efficacy , but also confirmed the old difficulties , mainly associated with the auricle 's fragility , and variable anatomy of the laa orifice , causing difficulties with device matching and thrombogenic potential of implanted devices [ 4 , 6 ] . the possible complications include laa tear , pericardial effusion or tamponade requiring drainage or surgery , acute stroke due to air or thrombus , device embolization or infection requiring its removal and incomplete closure or a leak to the laa after the procedure [ 4 , 7 , 8 ] . an overlooked issue is long exposure to x - ray radiation and high volume contrast infusion during the percutaneous procedure , whose long - term influence remains unexamined . the problem mainly associated with surgical approaches was the late recanalization , while incomplete closures were more typical for percutaneous techniques and were strictly associated with laa anatomy , which is currently one of the most important parameters in qualifying a patient for such a procedure [ 5 , 9 , 10 ] . the game remains risky since it has been proven that incomplete laa closure increases the risk of stroke to a higher level than leaving it open . another major question arose regarding generally the clinical relevance of such a procedure in large cohorts . to date , only one large trial has allowed the conclusion that effective laa exclusion prevents stroke , although the level of total occlusion in this trial was far from ideal . the above presented atriclip pro system used in terms of the first polish experience is a promising surgical technique for minimally invasive laa exclusion for primary and secondary stroke prevention in patients with persistent atrial fibrillation . the published data show that up to 100% efficacy with total laa exclusion , both in short - term and observation over a few years , is possible [ 912 ] . furthermore , apart from the excellent efficacy , no early or late complications such as bleeding , pericardial effusion , device malposition , or infection within 3 years have been revealed and , what is of utmost importance , no stroke was observed during this period although the mean chads2-vasc score was 4 ( about 10% yearly stroke risk ) and half of the patient group was off oral anticoagulation therapy . , the anatomy of the left atrial appendage has been a crucial factor influencing the results , but also one contraindicating the percutaneous procedure in some situations . it is also important that during the procedure the clip can be repeatedly reopened and repositioned under the simultaneous transesophageal control in case of any suspicion of incomplete occlusion or remnant , in order to achieve the optimal result . the problem of recanalization or residual leak has been recently raised for surgical laa closure within the left atrium . in none of our cases was the laa remnant ( stump ) bigger than 1 cm or a leakage to the excluded laa observed , which was an important finding taking into account that their presence significantly increases the risk of stroke ( even more than leaving the laa open ) and which may be some limitation of other technologies [ 14 , 15 ] . also in a prospective study of an epicardial device for laa closure there was no remnant or residual leak in long - term follow - up . what should be emphasized is that the implantation of the atriclip system does not require x - ray radiation or intravenous contrast administration , which might be a significant advantage since very many patients qualified for laa exclusion are multimorbid , with impaired renal function . the access site is reduced to three 1 - 2 cm incisions on the left side of the chest . the procedural skin - to - skin time reaches less than 40 minutes and patients are extubated at once after the operation . patients can be discharged from the hospital on the second or third postoperative day . from the practical point of view it is important that the implantation setup does not require an x - ray arm or hybrid operating room , although close cooperation with an experienced echocardiographer is recommended . limitations of the procedure are few , but still its invasiveness should be mentioned . a history of surgery within the pericardium and/or left pleural cavity as well as the presence of thrombus within the laa are contraindications for totally thoracoscopic laa clipping . the advantages of the procedure are presented in table iii . due to the balance between the advantages and disadvantages of surgical thoracoscopic and percutaneous approaches ( similarly to the field of persistent atrial fibrillation ablation ) a prospective randomized trial may be recommended . advantages of the procedure laa left atrial appendage additionally , electrical isolation of the laa from the left atrium accompanying the implementation of the atriclip was described . in a few cases it was associated with the cure of atrial fibrillation . it may be concluded that stand - alone laa exclusion / occlusion opens new very interesting , promising but also challenging perspectives . cardiac surgeons in cooperation with cardiologists the protect af trial has guided the way towards the new indication and therapeutic option , and further clinical research has to be undertaken . our first experience with the new totally thoracoscopic laa clipping system is very promising , showing very high efficacy and a good safety profile .
introductionatrial fibrillation ( af ) is the most common clinically relevant arrhythmia and it is strongly associated with stroke . left atrial appendage ( laa ) is considered to be the most often source of thrombotic material . in recent decades a number surgical , percutaneous and hybrid approaches for laa occlusion have been described revealing very different level of success and showing a variety of challenges associated with this matter . we present the first polish experience with the stand - alone totally thoracoscopic laa exclusion using novel clipping system.material and methodsfour patients ( one male ) in mean age of 74 ( 13 ) years with long - standing persistent and chronic af were admitted for totally thoracoscopic laa exclusion . all patients had significant comorbidities and the history of the oral anticoagulation intolerance or suboptimal / unstable level ( cha2ds2-vasc > 5 , has_bled > 3 ) . three procedures were performed through totally thoracoscopic access . in one patient due to massive adhesions in the left pleura we performed minithoracotomy in fourth left intercostal space . in two months follow - up we observed no mortality , no strokes and no bleedings.resultsin all patient total exclusion of laa with no residual remnant was confirmed . the skin - to - skin procedural time took on average 40 , minimum 20 minutes . patients were extubated directly or within two hours after procedure . all patients were discharged early in a good condition.conclusionsour initial first experience with the novel totally thoracoscopic clipping system for stand - alone laa exclusion is very promising showing very high efficacy and good safety profile .
SECTION 1. PEDIATRIC LABELING OF DRUGS AND BIOLOGICAL PRODUCTS (a) In General.--Subchapter A of chapter V of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 351 et seq.) is amended by inserting after section 505A the following: ``SEC. 505B. PEDIATRIC LABELING OF DRUGS AND BIOLOGICAL PRODUCTS. ``(a) New Drugs and Biological Products.-- ``(1) In general.--A person that submits an application (or supplement to an application)-- ``(A) under section 505 for a new active ingredient, new indication, new dosage form, new dosing regimen, or new route of administration; or ``(B) under section 351 of the Public Health Service Act (42 U.S.C. 262) for a biological product license; shall submit with the application the assessments described in paragraph (2). ``(2) Assessments.-- ``(A) In general.--The assessments referred to in paragraph (1) shall contain data, gathered using appropriate formulations, that are adequate-- ``(i) to assess the safety and effectiveness of the drug, or the biological product licensed under section 351 of the Public Health Service Act (42 U.S.C. 262), for the claimed indications in all relevant pediatric subpopulations; and ``(ii) to support dosing and administration for each pediatric subpopulation for which the drug, or the biological product licensed under section 351 of the Public Health Service Act (42 U.S.C. 262), is safe and effective. ``(B) Similar course of disease or similar effect of drug or biological product.--If the course of the disease and the effects of the drug are sufficiently similar in adults and pediatric patients, the Secretary may conclude that pediatric effectiveness can be extrapolated from adequate and well-controlled studies in adults, usually supplemented with other information obtained in pediatric patients, such as pharmacokinetic studies. ``(3) Deferral.--On the initiative of the Secretary or at the request of the applicant, the Secretary may defer submission of some or all assessments required under paragraph (1) until a specified date after approval of the drug or issuance of the license for a biological product if-- ``(A) the Secretary finds that-- ``(i) the drug or biological product is ready for approval for use in adults before pediatric studies are complete; or ``(ii) pediatric studies should be delayed until additional safety or effectiveness data have been collected; and ``(B) the applicant submits to the Secretary-- ``(i) a certified description of the planned or ongoing studies; and ``(ii) evidence that the studies are being conducted or will be conducted with due diligence. ``(b) Marketed Drugs and Biological Products.--After providing notice and an opportunity for written response and a meeting, which may include an advisory committee meeting, the Secretary may by order require the holder of an approved application relating to a drug under section 505 or the holder of a license for a biological product under section 351 of the Public Health Service Act (42 U.S.C. 262) to submit by a specified date the assessments described in subsection (a) if the Secretary finds that-- ``(1)(A) the drug or biological product is used for a substantial number of pediatric patients for the labeled indications; and ``(B) the absence of adequate labeling could pose significant risks to pediatric patients; or ``(2)(A) there is reason to believe that the drug or biological product would represent a meaningful therapeutic benefit over existing therapies for pediatric patients for 1 or more of the claimed indications; and ``(B) the absence of adequate labeling could pose significant risks to pediatric patients. ``(c) Delay in Submission of Assessments.--If a person delays the submission of assessments relating to a drug or biological product beyond a date specified in subsection (a) or (b)-- ``(1) the drug or biological product-- ``(A) shall be deemed to be misbranded; ``(B) shall be subject to action under sections 302 and 304; and ``(C) shall not be subject to action under section 303; and ``(2) the delay shall not be the basis for a proceeding to withdraw approval for a drug under section 505(e) or revoke the license for a biological product under section 351 of the Public Health Service Act (42 U.S.C. 262). ``(d) Waivers.-- ``(1) Full waiver.--At the request of an applicant, the Secretary shall grant a full waiver, as appropriate, of the requirement to submit assessments under subsection (a) or (b) if-- ``(A) necessary studies are impossible or highly impracticable; ``(B) there is evidence strongly suggesting that the drug or biological product would be ineffective or unsafe in all pediatric age groups; or ``(C)(i) the drug or biological product-- ``(I) does not represent a meaningful therapeutic benefit over existing therapies for pediatric patients; and ``(II) is not likely to be used for a substantial number of pediatric patients; and ``(ii) the absence of adequate labeling would not pose significant risks to pediatric patients. ``(2) Partial waiver.--At the request of an applicant, the Secretary shall grant a partial waiver, as appropriate, of the requirement to submit assessments under subsection (a) with respect to a specific pediatric subpopulation if-- ``(A) any of the grounds stated in paragraph (1) applies to that subpopulation; or ``(B) the applicant demonstrates that reasonable attempts to produce a pediatric formulation necessary for that subpopulation have failed. ``(3) Labeling requirement.--If the Secretary grants a full or partial waiver because there is evidence that a drug or biological product would be ineffective or unsafe in pediatric populations, the information shall be included in the labeling for the drug or biological product. ``(e) Meetings.--The Secretary shall meet at appropriate times in the investigational new drug process with the sponsor to discuss background information that the sponsor shall submit on plans and timelines for pediatric studies, or any planned request for waiver or deferral of pediatric studies.''. (b) Conforming Amendments.-- (1) Section 505(b)(1) of the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355(b)(1)) is amended in the second sentence-- (A) by striking ``and (F)'' and inserting ``(F)''; and (B) by striking the period at the end and inserting ``, and (G) any assessments required under section 505B.''. (2) Section 505A(h) o the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 355a(h)) is amended-- (A) in the subsection heading, by striking ``Regulations'' and inserting ``Pediatric Study Requirements''; and (B) by striking ``pursuant to regulations promulgated by the Secretary'' and inserting ``by a provision of law (including a regulation) other than this section''. (3) Section 351(a)(2) of the Public Health Service Act (42 U.S.C. 262(a)(2)) is amended-- (A) by redesignating subparagraph (B) as subparagraph (C); and (B) by inserting after subparagraph (A) the following: ``(B) Pediatric studies.--A person that submits an application for a license under this paragraph shall submit to the Secretary as part of the application any assessments required under section 505B of the Federal Food, Drug, and Cosmetic Act.''. (c) Final Rule.--Except to the extent that the final rule is inconsistent with the amendment made by subsection (a), the final rule promulgating regulations requiring manufacturers to assess the safety and effectiveness of new drugs and biological products in pediatric patients (63 Fed. Reg. 66632 (December 2, 1998)), shall be considered to implement the amendment made by subsection (a). (d) No Effect on Authority.--Section 505B of the Federal Food, Drug, and Cosmetic Act (as added by subsection (a)) does not affect whatever existing authority the Secretary of Health and Human Services has to require pediatric assessments regarding the safety and efficacy of drugs and biological products in addition to the assessments required under that section. The authority, if any, of the Secretary of Health and Human Services regarding specific populations other than the pediatric population shall be exercised in accordance with the Federal Food, Drug, and Cosmetic Act (21 U.S.C. 301 et seq.) as in effect on the day before the date of enactment of this Act.
Amends the Federal Food, Drug, and Cosmetic Act to require license applications for new drug and biological product to assess such drug's or product's safety and effectiveness for relevant pediatric subpopulations, including dosage.Permits extrapolation from adult studies where the course of the disease and the effects of the drug are sufficiently similar in all populations.Permits deferral of such assessments if adult studies are completed earlier and the applicant submits a plan for or a description of planned or ongoing pediatric studies.Authorizes the Secretary of Health and Human Services to specify a date for submission of pediatric assessments if a drug's or product's use or need in the pediatric populations so dictates. States that drugs or products with delayed assessments will be deemed misbranded and subject to seizure and injunctive proceedings, though not penalties.Permits full waiver of such assessments if: (1) studies are highly impracticable or impossible and the evidence suggests that the drug or product would be ineffective or unsafe in all pediatric age groups; or (2) there is no meaningful therapeutic advantage or benefit in the pediatric population and little risk if used as labeled. Permits partial waivers at the request of an applicant for a specific pediatric subpopulation if any of the full waiver grounds apply to that subpopulation or reasonable attempts for a pediatric formulation for that subpopulation have failed. Requires labels of these drugs or products to reflect such waivers.
Here’s a seemingly simple question: When is Tax Day this year? Even for the most tax-law-challenged taxpayers, the answer might seem obvious: Individual income-tax returns are due April 15, a date as memorable to most Americans as the joyful holidays of Jan. 1, July 4 or Dec. 25. Simple but wrong—for this year and last year and next year, for that matter. When it comes to taxes, it seems that rarely is anything truly simple, even Tax Day. The deadline can vary depending on several factors, such as the timing of weekends and the celebration of Emancipation Day in the District of Columbia. The date also may vary for millions of people, depending on various state holidays and even the timing of natural disasters such as severe storms and tornadoes. So for most taxpayers this year, T-Day falls on April 18. Here is a mercifully brief explanation: Thanks to Lincoln April 15 this year falls on a Saturday. So it might be logical to assume that would push the tax-filing deadline back to Monday the 17th. No, because that’s the day that Washington, D.C., will observe Emancipation Day this year. That refers to emancipation from slavery, not taxes: the celebration of when President Abraham Lincoln signed a law on April 16, 1862, to end slavery in Washington. This year, the 16th is a Sunday, making Monday the 17th the day on which Emancipation Day is observed—and bumping back the filing deadline for most people to Tuesday the 18th. “By law, D.C. holidays impact tax deadlines for everyone in the same way federal holidays do,” the IRS explained earlier this year. Thus, the April deadline for filing and paying whatever might be owed to Uncle Sam for the 2016 tax year is Tuesday, April 18 — at least for most taxpayers. But not all. Many people in parts of Georgia and Mississippi have until May 31 to file and pay, and parts of Louisiana get until June 30, an IRS spokesman says. There are other exceptions, too—as well as different deadlines in some states. The IRS can postpone certain deadlines for taxpayers who live, or have a business, in places designated as a federal disaster area. That’s why some parts of Georgia, Mississippi and Louisiana have been given later filing deadlines this year. (For details, see the IRS website: irs.gov and look under “Tax Relief in Disaster Situations.”) There are other deadlines for many taxpayers living and working abroad, as well as for members of the military serving in a combat zone. For millions of procrastinators, of course, the April filing deadline simply means the deadline for requesting more time to file. They can ask the IRS for an additional six months, says Jeffery L. Yablon, a partner at Pillsbury Winthrop Shaw Pittman LLP in Washington who has compiled a splendid collection of quotes, quips and pithy sayings about taxes. (Here is one example: “Taxes: Of life’s two certainties, the only one for which you can get an automatic extension.” Yablon attributes that to “anonymous,” but reliable sources say it comes from a book called “Buzzwords” by John Freund and David Porter.) To get a six-month filing extension, you don’t even need to give a reason. But that doesn’t give you more time to pay whatever you might owe. It only gives you more time to file. However, a six-month extension won’t extend the deadline until Oct. 18. Instead, it will extend it to Monday, Oct. 16, the IRS says. The IRS hasn’t officially set the filing date yet for 2018, but it definitely won’t be April 15 since that will fall on a Sunday. While it’s hazardous to make any predictions about subjects involving taxes, especially this year, reliable sources say, based on the latest IRS guidance, T-Day 2018 will fall on April 17—thus marking the third year in a row that the dreaded date won’t be April 15. The filing date in 2016 was tricky, too. Here’s how the IRS explained it a year ago: “Taxpayers have until Monday, April 18 to file their 2015 tax returns and pay any tax due because of the Emancipation Day holiday in Washington, D.C., falling on Friday, April 15. Taxpayers in Maine and Massachusetts will have until Tuesday, April 19 because of Patriots’ Day observances on April 18.” While many states follow the federal custom, some don’t. When in doubt, check with your state tax department. Why not scrap the April T-Day madness? Accountants, enrolled agents and other tax preparers have complained for years about the annual stresses of the April filing deadline, especially since so many perplexed clients wait until the 11th hour to share their shoeboxes stuffed with W-2 forms, 1099s, charitable-giving receipts and stacks of other documents. Vote for change? Some people have suggested moving the deadline to Election Day—or moving Election Day to April — so that voters will focus more closely on what they get compared with what they pay. However, to change the date, congressional action would be required. And the path to congressional action on most tax-related subjects may be one of the few areas at least as complicated as our tax laws themselves. ||||| While many despise Tax Day, companies across America are using the day to offer their best discounts to customers. Look below for a list of top deals on Tax Day, which is on Tuesday, April 18. NOTE: The following offers apply only to participating locations. Bob Evans: The "Down on the Farm" restaurant is offering 30 percent off orders on Tax Day on almost all orders with this coupon. Bruegger's Bagels: For the seventh straight year, Bruegger's is offering its bagel bundles for $10.40, a discount of $3.50. The deal currently runs through April 19. Firehouse Subs: Customers can get a free medium sub with the purchase of a medium or large sub, chips and drink with this coupon. The deal runs from Tuesday through Thursday. Great American Cookies: Stop by a Great American Cookies location on Tuesday and receive a free Birthday Cake Cookie. the company says that no purchase or proof of completed taxes necessary. Hooters: At participating locations, Hooters is offering free kids meals through Tuesday with the purchase of an adult entree. The deal is dine-in only. Hot Dog on a Stick: Fans of corn dogs might enjoy Hot Dog on a Stick's offer of a free Original Turkey Dog on Tuesday. The company says that no purchase is necessary, and there is a limit of one free dog per customer. Kona Ice: Kona Ice trucks will be parked at various post officers and shopping centers across the America on Tuesday, serving free cups of tropical shaved ice. To find the location closest to you, tweet @KonaIce with your zip code. McDonald's: McDonald's Tax Day deal features a 1-cent Quarter Pounder with Cheese or Big Mac with the purchase of a full-price Quarter Pounder with Cheese or Big Mac at select Florida locations. The deal is for Tuesday only. Schlotzsky's: Schlotzsky's is offering a free Original sandwich on Tuesday with the purchase of a medium drink and a bag of chips. Sonic Drive-In: In addition to offering milkshakes and ice cream slushes for half price after 8 p.m., Sonic Drive-in will have half-price cheeseburgers on Tuesday. World of Beer: Participating locations are offering a free select draught beer on Tax Day. Find another great Tax Day deal? Share with reporter Justin Boggs on Twitter. ||||| In this photo taken Jan. 4, 2013, from Air Force One, with then-President Barack Obama aboard, shows the White House, Washington Monument, Jefferson Memorial, downtown Washington and Ronald Reagan National... (Associated Press) In this photo taken Jan. 4, 2013, from Air Force One, with then-President Barack Obama aboard, shows the White House, Washington Monument, Jefferson Memorial, downtown Washington and Ronald Reagan National Airport during the president's return from a day trip to Minneapolis before landing at Andrews... (Associated Press) In this photo taken Jan. 4, 2013, from Air Force One, with then-President Barack Obama aboard, shows the White House, Washington Monument, Jefferson Memorial, downtown Washington and Ronald Reagan National Airport during the president's return from a day trip to Minneapolis before landing at Andrews... (Associated Press) In this photo taken Jan. 4, 2013, from Air Force One, with then-President Barack Obama aboard, shows the White House, Washington Monument, Jefferson Memorial, downtown Washington and Ronald Reagan National... (Associated Press) WASHINGTON (AP) — As Tax Day approaches, show some love for the good people who live in the nation's capital. Washington, that swampy den of iniquity that politicians love to scorn, sends the most tax dollars per person to the U.S. government. By a lot. Last year, the District of Columbia paid Uncle Sam $37,000 per person in federal income, payroll and estate taxes. The next closest was Delaware, at $16,000 per person. "It's where the money is," said Roberton Williams, a fellow at the Tax Policy Center. "The reason the District pays so much in taxes is that there are a lot of high-income people there." Washington is an outlier because, despite years of lobbying, it is not a state. It doesn't even have a vote in Congress. It is, however, a city with a relatively high cost of living. West Virginia, Mississippi and New Mexico have low median household incomes, which helps explain why they their residents pay far less in federal taxes. West Virginia paid $3,600 per person last year, while Mississippi paid $3,900 per person and New Mexico residents paid a little more than $4,000. The Associated Press calculated each state's per-capita tax bill using data from the IRS and population estimates from the Census Bureau. The deadline to file federal tax returns is Tuesday. It was pushed back because the usual April 15 deadline was Saturday, and because Monday is a holiday in the District of Columbia. The IRS says millions of taxpayers have yet to file their returns. As they do, they shouldn't feel too bad for D.C. residents. The nation's capital gets a good return on its tax investment. For every dollar the District sends to the federal government, it gets back almost $4, according to a 2015 study by the New York state comptroller. For years, the late Sen. Daniel Patrick Moynihan, D-N.Y., would document that New York paid more to the federal government than it got back. In 2015, the state's comptroller took up the cause. Washington's rate of return is higher than any state — most of it comes from wages for federal employees. The closest state is Mississippi, which gets back $2.57 in federal spending for every dollar it sends to Washington. New Mexico, West Virginia and Alabama are also big winners when it comes to federal taxes and spending. These states are big takers because they have a lot of residents who get federal benefits, including Social Security, Medicare, Medicaid, disability benefits and food stamps. "They have lower incomes so they pay less in taxes and, because they have lower incomes, they get more federal aid," said Morgan Scarboro, a policy analyst at the Tax Foundation. So why do so many of these states that benefit from the federal government produce conservative politicians who complain that the government is too big? "There is this perception that so much money is being spent on things that don't benefit them," Williams said. "They ignore the things that do benefit them." Williams cited foreign aid as a favorite target, even though it makes up only 1 percent of the federal budget, if you count military assistance. "People view the world as cut my taxes and cut his spending," Williams said. "His spending is wasteful and my taxes are hurting me badly." Most states are winners when it comes to getting more money from the federal government than they pay in taxes. On average, Americans get $1.22 for every dollar they send to Washington, according to the New York study. That's why the federal government has a budget deficit. The federal spending comes from social programs such as Social Security, Medicare and Medicaid, as well as grants to state and local governments and spending on infrastructure. States such as South Carolina, North Carolina and Virginia benefit from having large military bases. The biggest losers when it comes to taxes and spending are New Jersey, Wyoming and Connecticut. New Jersey gets back just 77 cents for every dollar it pays, while Wyoming gets back 81 cents and Connecticut gets 83 cents. New York gets 91 cents for every dollar it sends to Washington, according to the comptroller's report. All these states have incomes above the national average. "It's a good example of a progressive tax code," Scarboro said. "That is how it is designed to work." ___ Follow Stephen Ohlemacher on Twitter at: http://twitter.com/stephenatap ||||| There is a $2,850 check with your name on it just waiting for you. All you need to do is file a few forms and it’s yours. You have three months to claim it. How quickly would you act? If you are like the authors, your answer is right away! Sadly, this is not what people do. Instead, they wait. Last year, 73 percent of tax filers received a tax refund of $2,860, on average. That is roughly one month’s net pay for the median income household in the United States. According to the IRS, 25 percent of tax filers submitted their taxes between April 1st and April 22nd. In addition, 10 percent of tax filers submitted their taxes after the deadline. Filing statistics for tax year 2015. Credit: Internal Revenue Service So why are people waiting to file? One explanation could be that people who wait until the last minute to file are the ones who won’t receive a refund. If this is the case, these people are being rational and optimizing the timing of their financial outlay. However, this does not seem to be the case for everyone. Roughly 32 percent of all tax refunds are given out after April 1. That’s 35 million people who are waiting to claim their check! Some may be tempted to say that people who wait until the last minute to file their taxes just don’t like free money. This is clearly absurd. Yet, this line of thinking is used by many business leaders and product managers. We assume that product uptake is a direct function of people’s preferences or interest. Let’s take a look at an example of this. Imagine you’re an employer and are offering a 3 percent 401(k) matching program. This will allow your employees to get thousands of dollars toward their retirement. After launching the program you see a dismal uptake rate of 40 percent. As an employer you must decide if you should continue the program. You might decide to discontinue it, since the majority of employees have not claimed their cash. People must not want to save. Maybe they don’t like savings, or maybe they don’t have enough money to save for retirement. John Beshears, James Choi, David Laibson, and Brigitte Madrian challenged this line of thinking and designed an easier enrollment option for employer 401k matching programs. This intervention increased enrollment rates by 10-20 percentage points. What’s the lesson? Our inactions reflect both our preferences and our decision making environment. It’s not that people hate savings. It’s that the old enrollment flow was cumbersome. People have busy and complicated lives. Anything that takes considerable time and effort often times gets pushed off to the imaginary time-rich tomorrow. Tax filing suffers the same fate. On average the IRS expects non-business filers to have an average burden of about nine hours and payment of $120 to file. While the benefit of free money may loom large, what likely looms larger is the complexity and time costs of filing. When things are complex, we procrastinate, even when the payoff is exceptionally high. Good news. There is a silver bullet, called a “deadline.” We partnered with another social impact company, the Kiva U.S. team at Kiva.org to fully understand the power of deadlines. Kiva U.S. crowdfunds interest-free loans to small businesses in the United States. To qualify, applicants must fill out eight pages of information. This includes detailed information about the business’s revenue and accounting, a picture of the business and social media information about the business. While this is long process, the payoff (a zero-interest loan for your business) is massive. When we added a simple deadline to finish the loan application, 24 percent more people completed it. The tax day deadline is typically associated with stress—so much so that car accidents are shown to rise on April 15th. However, it’s possible we may want to be grateful there is a deadline that puts us out of our misery and helps us claim our check. Food for thought: Let’s make it March 15 instead of April 15 We can strengthen the power of deadlines by decreasing the time of the deadline. For example, Suzanne Shu and Ayelet Gneezy found that longer deadlines, compared to shorter deadlines, encourage people to procrastinate, even on things they like to do, like claiming free spa certificates! Most of us can file right after we get our W-2s and 1099 tax forms in January or February. Maybe we can eliminate late filers by making the deadline earlier rather than extending it. Special thanks to MetLife Foundation for supporting Common Cents. MetLife Foundation believes that everyone should have access to the right financial tools and services to build a better tomorrow. ||||| We Asked People What They Know About Taxes. See If You Know The Answers Back in 2012, Republican presidential nominee Mitt Romney's campaign suffered a blow when a tape was leaked of him grousing that 47 percent of Americans don't pay federal income tax. It was one of the biggest gaffes of the presidential campaign, but a new poll conducted by Ipsos for NPR suggests that many Americans forgot it. The way Romney characterized those who don't pay federal income taxes is what got him in trouble, but the figure was roughly true. The new poll, however, shows that a majority think that the share of Americans paying no federal income tax is far lower. The poll gave respondents four options — 39 percent said that only 11 percent of Americans pay zero or negative income tax, and 31 percent said that only 27 percent pay zero or negative income tax. Only 21 percent got it right — right now, around 45 percent pay no federal income tax. The poll, released the day before Americans' taxes are due, delved into what Americans know and what they believe is wrong with the U.S. tax code — and what they know is limited and at times contradictory. But this isn't just about pointing out what Americans know and don't know. Rather, there could be important policy implications to Americans' misperceptions about the tax system. For example, this question dovetails with questions about what people think the lowest-income Americans' tax rate should be. Americans underestimate the share of Americans who don't pay federal income taxes Given four choices of how many Americans pay zero or negative federal income taxes (11, 27, 45, or 63 percent), fully 70 percent of poll respondents chose the options under the correct answer, which was 45 percent. Some of these people simply have no taxable income, and others get money back as a result of refundable tax credits like the Earned Income Tax Credit. (Of course, these people might pay other taxes, like payroll taxes, as well as whatever sales and property taxes their states impose.) Two-thirds of Americans believe lower-income people pay too much income tax (with heavy partisan differences — around 8-in-10 Democrats, 6-in-10 independents, and half of Republicans agreed with that statement). In addition, 60 percent of Americans believe taxes should be lowered for people making $49,000 or less (again, with Democrats and independents being somewhat more likely than Republicans to say those taxes should be lowered). Taking these two ideas together — that people (mistakenly) think very few of their fellow Americans pay zero federal income tax, and that a majority of Americans think low-income people pay too much in income tax — there are a couple of possible conclusions. One is that if more Americans knew how many others do not end up paying federal income taxes, they would say tax rates should stay the same or even be raised. Then again, it's possible that Americans nevertheless would think their poorest fellow citizens do need more money, regardless of how the current tax code looks. That might mean they would advocate expanding the EITC or other tax breaks. When it comes to taxes paid by the rich, things get complicated. We posed the following statement to people as a true or false question: "For the highest earners, the percent of federal income taxes they pay now is significantly higher than it was in 1980." In retrospect, there are multiple ways to interpret this question. If "percent" is taken as "rate" here, the answer is "false." In 1980, the top marginal income tax rate was 70 percent. Today, it's 39.6 percent (something about half of Americans know, per our poll). But if "percent" is taken as "share" here, the answer is "true." That is, the share of federal income tax revenue that the richest Americans pay has gone up since 1980. How does that work? As the Tax Policy Center's Roberton Williams explained to NPR, the share of income going to the rich has climbed in a big way over the last few decades. So how Americans think about this could affect what they think should happen to the top tax rates on the richest. In 1980, the top 10 percent brought in 32 percent of all adjusted gross income, according to the Tax Foundation. In 2013, it was 46 percent. For example, many Americans also believe taxes should be raised on the richest. The top tax bracket starts at $418,400 right now. The poll shows that 70 percent of Americans believe taxes should be raised on people making $250,000 to just under $1 million, and that 75 percent believe they should be raised on people making $1 million or more. That's already a sizable majority, but depending on whether people knew tax rates on the richest had indeed fallen (or, alternately, that the rich now pay a higher share in taxes), it could change what they think should happen to those marginal rates. (Of course, it's also possible that historical rates wouldn't affect their views at all.) Those views differ widely by party; Democrats are much more likely to believe that taxes should be raised on the rich than Republicans. Americans also appear to have strong views on how people earn their money. We asked people to what degree they agreed with this statement: "The tax rate on income from work should be lower than the tax rate on income from wealth." Across the board, regardless of party, Americans agreed — 75 percent said they did, including 77 percent of Democrats, 71 percent of Republicans and 84 percent of independents. This is another result that might make the richest Americans squirm. The rich tend to earn their income in a different way from most other Americans. Besides paychecks, many make money from capital gains — income they get from selling investments like stocks. Most of those capital gains are taxed at a rate far below that top income tax rate. (People at any income level of course can have those kinds of investments, but capital gains are overwhelmingly concentrated at the top of the income spectrum.) The top rate that the highest-income Americans will pay on most capital gains is 20 percent, around half the top marginal rate for ordinary income. Americans overestimate how important income taxes are to government revenue About half of the poll's respondents (with very little variance by party) said they believe 75 percent of the federal government's revenue comes from personal income taxes. In reality, it's just under half. Of all the taxes Americans pay, income tax probably requires the most thought. After all, payroll tax comes automatically out of each paycheck. Sales tax is imposed at the cash register. And so on. So maybe it makes sense that Americans think all that work they put into filling out their forms ends up doing the lion's share of funding the government. What else we learned Beyond all this, there were a few more fascinating findings in the poll. Phrasing matters. One thing we learned is that using the phrase "death tax" instead of "estate tax" seems to make people more opposed to that tax — but, interestingly, that effect appears to be by far largest among Democrats. Sixty-five percent of all people said the "estate tax" should be abolished, compared to 76 percent who said the "death tax" should be. However, among Democrats that swing was far larger: only half said they wanted to abolish the "estate tax," but 71 percent said the same of the "death tax." The estate tax affects fewer than 1 in 500 estates. Many opponents of the estate tax — who have tended to be Republicans — use "death tax" as a euphemism. This shows that to the extent that that phrasing helps them, it could be helping them pick people up across the aisle. On tax policy, views aren't always all that partisan. Democrats are often seen as the party that wants a more progressive system — Hillary Clinton, for example, ran for president in 2016 with a tax plan that would have ramped up taxes for the ultra-rich. But in our poll, nearly half of Democrats — 45 percent — agreed with the proposition that "federal income taxes should be cut for all income levels." Likewise, Republicans — the party that has spoken of "makers" and "takers" — were split roughly evenly on the idea that tax cuts for the wealthy lead to economic growth. (Democrats and independents tended to disagree — that is, to say that tax cuts for the wealthy do not lead to that growth.) Incidentally, it's not at all clear that this is true; one recent comparison of tax rates and growth rates across advanced economies found no strong linkage between the two. These are only two examples, but they suggest that partisan messaging in Washington on some specific issues doesn't necessarily filter down to Americans. Americans agree: Taxes are too complicated (but that's no reason to cheat). There are a few more areas where Americans tend to agree across party lines: nearly 9 in 10 believe the tax code is too complicated, three-quarters say it's not OK for people to underreport income on their taxes, and 77 percent say their own personal federal income taxes are too high. In addition, 72 percent knew that taxes are due on April 18. For those remaining 28 percent, it might be time to file that extension. The poll was conducted online on April 11-12, with a sample of 1,010 adults age 18 or older. For all respondents, the poll has a credibility interval of plus or minus 3.5 percentage points. The credibility interval is plus or minus 5.7 percentage points for Democrats, plus or minus 6.1 percentage points for Republicans, and plus or minus 8.3 percentage points for independents. ||||| Investors, traders and the financial media are struggling to discover the exact reasons behind the market's recent woes. Geopolitics is the latest scapegoat, followed closely by President Donald Trump's renewed commitment to difficult health-care reform before tackling tax cuts. But Josh Brown, whose instincts are usually on the money about this sort of stuff, tweeted this out at the end of last week: We ran the numbers on the market's performance around Tax Day going back to 1980 and turns out Josh could be exactly right. According to hedge fund analytics tool Kensho, here is the average performance of some major market benchmarks during the two weeks before Tax Day, which falls on Tuesday: The S&P 500 is barely in the green, on average. The Nasdaq composite, which contains tech stocks popular with retail investors, and the Russell 2000 index, a holder of smaller stocks typically owned more by individuals than institutions, actually average a loss. Now look what happens in the two weeks after Tax Day, on average: The average gain quadruples for the S&P 500, and the Russell 2000 and Nasdaq go from average losses to increases greater than 1 percent. The probability of a gain during those two weeks vs. the two before Tax Day also increases significantly. So there seems to be a clear pattern. Like any of these seasonal patterns, it's more apparent during some years than others. This year is likely a good one for the trend, given the strong gains since the election. And doubts about tax reform being made law by the end of 2017 may also be exacerbating the tax-related selling this year. Disclosure: NBCUniversal, the parent of CNBC, is a minority investor in Kensho. ||||| For the past few years, I’ve sat in New Orleans high school classrooms watching students debate the fairest way for government to raise revenue. They role-play — first as management consultants advising legislators; then as lawmakers, weighing what to tax: property vs. sales vs. income. Are there limits on what or who can be taxed? Is a flat tax or a progressive rate structure fairer? Sometimes their discussions are heated. These teenagers, however, have an edge that many adults don’t: basic tax literacy. Guided by Tulane law students, the high schoolers explore different philosophies and methods of taxation through TaxJazz, a program I began in 2013. Students who take the week-long course study issues of fairness and technical matters such as bases and rate structures. They examine key concepts such as the difference between marginal rates (the percentage of tax paid on the last dollar of income) and effective rates (the average percentage of tax paid). They learn that narrower tax bases, such as sales tax, need higher rates than broader bases, such as income taxes, to raise equivalent amounts of revenue. They discover that changing the method of taxation increases how much some taxpayers owe and decreases that amount for others. If more people knew what these students know, we’d have a far more reasonable tax debate and better tax laws. As Tax Day approaches (April 18 this year), many of us bemoan our tax bills coming due. Why is taxation such a charged issue? Many Americans are fuzzy on who and what are taxed and the reasons we pay taxes at all. A year ago, 57 percent of Americans polled told Gallup they pay “too much” in federal income taxes; note, though, that 45 percent of Americans pay no federal income taxes at all. We fight about taxes because we disagree about what is fair and what government should do. If we knew more, we’d still have disagreements, but at least our discussions would be more rational and produce more coherent policies. Tax law can be complex, but if high school students can get a handle on the basics, so can the adults who choose the politicians who implement it. [Trump’s tax plan would mean huge breaks for millionaires] Is a flat or a progressive tax fairer? It depends on your sense of justice — but before you can even answer that question, you need to know how each mechanism works. So students learn that the relative tax burden on individuals depends on which tax base is used. Sales taxes place a higher burden on lower-income people, because lower-income taxpayers generally spend a greater percentage of their income than higher income taxpayers do. A flat income tax is easy to understand: You pay a certain percentage of your income, no matter how much you make. With a progressive income tax, escalating rates apply as income increases. For example, if a married couple had $52,000 of taxable income in 2016, the return they file this year will show a tax liability of $6,872.50 (assuming no tax credits). They will pay 10 percent on their first $18,550 and 15 percent on the rest of their taxable income. Their marginal rate is 15 percent, but their effective, or average, tax rate is 13.2 percent. Real-world discussions often occur in a tax-ignorant universe. Many people — including some politicians — incorrectly say that the IRS, not Congress, writes federal tax laws. They say that some taxation is needed to pay for the government but that it should be lower and “fairer.” An astonishing number don’t realize that they already get tax breaks for many things they want, such as education, housing and child care. Often they state that we should lower the income tax rate to a number that is actually higher than the current top rate. Some have no idea what rate they pay or whether they’ve benefited from a tax cut. Unfamiliarity with tax basics is harmful. At the individual level, people may pay more than necessary when they don’t know about deductions and credits that can reduce their burden. At the local, state and national levels, lack of tax knowledge hampers the promulgation of rational laws that could help spur the economy and lead to prudent budgets. A tax-literate electorate could demand that politicians provide coherent tax policy options. [Americans don’t mind paying taxes. But they want Trump to, also.] To be tax literate, citizens should understand that taxes are not just numbers and abstract principles, and they are not arbitrary. “Taxation is an art and a technique as well as science,” said Harold M. Groves, an economics professor who was a Wisconsin state legislator in the 1930s, “and it always needs to be judged against the conditions of time and place.” How can more Americans become tax knowledgeable? The first step, of course, is to include more discussion of taxes in schools — not just in high school and college, but even elementary school. This is no less important than the financial-literacy programs many schools now incorporate into their curriculums. Without tax knowledge, voters enable politicians who spout inflammatory, empty rhetoric and perpetuate counterproductive, unfair tax policies. Democracies need informed voters to function properly. The cost of tax ignorance is too high.
– The deadline to file federal taxes this year is Tuesday, April 18, and procrastinators have Abraham Lincoln to thank for the extra time, explains MarketWatch. Tax Day is normally April 15, but not so this year because it fell on a weekend. Typically, that would mean it gets pushed to the following Monday, but because Washington, DC, observes Emancipation Day on Monday—the day Lincoln freed the slaves in the capital, which is actually April 16, but that, too, fell on a weekend—Tuesday it is. A look at coverage: Consider this stat: 57% of Americans think they pay too much in federal income taxes, but 45% of Americans actually pay no federal income taxes at all. How to explain the anomaly? Americans are seriously ignorant about taxes, writes Tulane prof Marjorie Kornhauser in the Washington Post. Progressive vs. flat? Marginal rates vs. effective rates? She's got some suggestions to remedy this, including teaching tax literacy in schools. Think you are among the tax literate? Prove it with a quiz from NPR. Sample question: The highest earners pay a significantly higher share of federal income taxes than they did in 1980. True or false? Which state sends the most tax dollars per person to the federal government? Delaware is tops at $16,000. However, Washington, DC, trumps all the states by a mile at $37,000, reports the AP. See where your state ranks here. As many people remember in the spring, filing taxes can be an "absurdly complex" process, writes TR Reid in the New York Times. He makes the case that it doesn't need to be this way, starting with the IRS pre-filling in our forms with the numbers it already knows. Tax Day may be behind the markets' recent struggles, explains a post at CNBC. A post at Scientific American floats the idea of moving Tax Day up a month to March 15. The idea is that, counter-intuitively, the shorter deadline will reduce the number of late filers. With Tax Day comes freebies at various businesses on Tuesday. ABC15 rounds them up, including a deal on Quarter Pounders at McDonald's.
lattice discretisation procedures are often used to define the partition functions of quantum theories . the resulting models are called state sum models , because the functional integral become a sum over a discrete set of states . these models typically depend on the particular lattice structure that is chosen , but in the limit as the lattice becomes increasingly fine , the model becomes a better approximation to the continuum theory . in topological quantum field theories , the model is independent of the choice of lattice structure , which is typically taken to be a triangulation of the spacetime manifold . such theories are of interest in quantum gravity because the partition function has the same symmetry as the classical theory , namely spacetime diffeomorphism symmetry . realistic quantum gravity models should include matter , and so it is important to consider models which incorporate matter while maintaining triangulation independence . with the recent discovery of the higgs boson at the lhc @xcite , it is now clear that scalar fields are an important part of our description of fundamental physics . this is our motivation for studying state sum models which include scalar fields . in this paper , a simple one dimensional model of a scalar field on a @xmath0-manifold is constructed . in section [ sec : state sum ] , the definition of the state sum model for a real scalar field on the interval and circle is developed . the model is independent of the triangulation and depends only on the holonomy of the gauge field . however , introduction of a mass term in a ` nave ' way breaks the triangulation independence . in section [ sec : interpretation ] , it is shown that the state sum model has a discrete action that has the continuum action for a minimally coupled scalar field as its continuum limit . in section [ sec : functional ] , the functional integral for the continuum theory on the circle is evaluated using zeta function regularisation , and it is shown to be exactly equal to the result from the state sum model for the gauge group @xmath1 . if the gauge group is chosen to be the group of strictly positive numbers under multiplication , the state sum model on the circle is equivalent to the path integral for the harmonic oscillator , or equivalently the massive scalar field in one dimension . thus it is possible to introduce a mass term into the model while maintaining triangulation independence if the mass parameter is treated in the same fashion as a gauge field . in the standard treatment of the path integral for the harmonic oscillator , the partition function is calculated as the limit of a discrete model that is not triangulation independent . the state sum model presented here has the virtue that it is triangulation independent and exactly equal to the partition function of the harmonic oscillator once the appropriate gauge group has been chosen . there is not much work on state sum models which incorporate scalar fields in the literature , perhaps because it was not known until recently if scalar fields exist in nature . however , the quantum mechanics of a particle in @xmath2 dimensions is in fact equivalent to a one dimensional quantum field theory of an @xmath2-plet of scalar fields , in precisely the same way that the quantum mechanics of a string in @xmath2 dimensions is equivalent to a two dimensional quantum field theory of an @xmath2-plet of scalar fields on the worldsheet . the path integral quantisation of the harmonic oscillator has been well explored ; however , in this paper we develop an alternate approach which is more in the spirit of quantum field theory . this work complements our previous work on fermions @xcite . it is an interesting question as to what extent the model here can be generalised to higher dimensions . we leave this for future investigation . start with an oriented interval @xmath3 $ ] of length @xmath4 , triangulated with @xmath5 vertices . the vertices are decorated with variables @xmath6 , each of which is a vector in @xmath7 . the edge connecting the @xmath8-th and @xmath9-th vertices is further subdivided into two segments by a vertex at its centre labelled by @xmath10 . each segment with initial vertex @xmath11 and final vertex @xmath12 is decorated with a real @xmath13 matrix @xmath14 . indeed we will use the more general notation that @xmath14 is equal to the product of the matrices connecting vertices @xmath11 and @xmath12 , which need not be adjacent , in the order determined by the orientation . these matrices satisfy @xmath15 . the length of each edge is @xmath16 . for now we assume that the matrices @xmath14 are orthogonal . the situation is depicted in figure [ interval figure ] . for @xmath17 , i.e. a single edge , the state sum model is @xmath18 with @xmath19 . gluing two edges together is carried out by multiplying their respective partition functions together and integrating over the variable associated to the interior vertex , @xmath20 where the integral is the lebesgue integral over @xmath7 , and now @xmath21 , @xmath22 . this can be evaluated using the following lemma , @xmath23 where @xmath24 , @xmath25 are real numbers , @xmath26 are real , orthogonal @xmath13 matrices , and the superscript @xmath27 denotes the matrix transpose . this can be proved by expanding the brackets and using gaussian integration . applying this to results in @xmath28 gluing @xmath29 edges together in this way yields the definition of the state sum model on an interval triangulated with @xmath5 vertices , @xmath30 } & = \left ( \frac{1}{2\pi \delta t } \right)^{\frac{nn}{2 } } \int \prod_{i=1}^{n-1 } { \mathrm{d}}\phi_i \ ; e^ { -\frac{1}{2\delta t } \sum_{i=0}^{n-1 } ( q_{i+\frac{1}{2},i}\phi_{i } - q_{i+\frac{1}{2},i+1 } \phi_{i+1})^2 } \label{interval0 } \\ & = \left ( \frac{1}{2\pi n \delta t } \right)^{\frac{n}{2 } } e^ { -\frac{1}{2 n \delta t } ( q_{m,0 } \phi_0 - q_{m , n } \phi_{n})^2 } \\ & = \left ( \frac{1}{2\pi l } \right)^{\frac{n}{2 } } e^ { -\frac{1}{2l } ( q_{m,0}\phi_0 - q_{m , n } \phi_{n})^2}. \label{scalar interval}\end{aligned}\ ] ] here @xmath31 denotes the vertex at the midpoint of the interval . the state sum model on the circle is obtained by identifying @xmath32 in and integrating , @xmath33 where @xmath34 , and @xmath35 on the circle , the orthogonality assumption for the @xmath36 s can be weakened ; they can now be assumed to be invertible only . the integral can be evaluated with a change of variables , yielding @xmath37 the determinant can be computed iteratively using the following fact , @xmath38 where @xmath39 , @xmath40 , @xmath41 , @xmath42 are @xmath43 , @xmath44 , @xmath45 and @xmath46 matrices , respectively , and @xmath42 is invertible . the result is @xmath47 where @xmath48 is the holonomy around the circle . the partition function on the interval has the property of triangulation independence . that is , it is independent of @xmath29 , the number of sides of the polygon . this is also true of the partition function on the circle , provided some further stipulations are placed on the @xmath36 s . in the case where the @xmath36 s are elements of @xmath49 , and @xmath50 with @xmath51 , @xmath52 , the partition function is given by @xmath53 more generally , if @xmath36 is an orthogonal matrix , it may be diagonalised to the following canonical form @xmath54 where the @xmath55 , @xmath56 are independent @xmath57 rotation blocks . it is clear that under certain circumstances the denominator in can be zero , in which case the model is not defined . this occurs if @xmath36 is odd - dimensional . thus this scenario is excluded from consideration . then the partition function decomposes as the product of a number of @xmath49 theories . in the case where @xmath58 with @xmath59 and @xmath60 the @xmath13 identity matrix , the partition function is @xmath61 the state sum model presented here can be straightforwardly generalised to the case where the @xmath62 are complex vectors . in this case , where it occurs the orthogonality requirement for the matrices @xmath14 is replaced by unitarity , and the partition functions , are the same but for twice as many real degrees of freedom . the state sum model of the previous section may be interpreted as the partition function of a minimally coupled , real scalar field theory . the @xmath62 s are interpreted as a discrete sampling of a continuous real scalar field @xmath63 on the circle , with @xmath64 , so that @xmath65 the interval connecting vertices @xmath11 and @xmath12 is assigned the matrix @xmath14 , which is interpreted as the parallel transporter for the @xmath66 field along that interval . then @xmath67 , with @xmath68 the gauge field on the circle . up to a minus sign , the argument of the exponent in may be seen to be a lattice discretisation of the usual action for a scalar field , @xmath69 the limit @xmath70 , or equivalently @xmath71 , while keeping @xmath4 constant can be evaluated , @xmath72 where @xmath73 is the covariant derivative . this is just the usual continuum action for a scalar field . thus the partition function may be interpreted as that of a real , minimally coupled scalar field . it is possible to add a mass term to the action , @xmath74 however , the resulting partition functions on the interval and circle are no longer triangulation independent . if the gauge group is taken to be isomorphic to the abelian group of strictly positive real numbers under multiplication so that @xmath75 , then @xmath76 . \label{massive scalar}\end{aligned}\ ] ] here the gauge freedom has been used to transform the gauge field @xmath68 so that it is everywhere equal to a constant @xmath77 . identifying @xmath63 with the @xmath2-dimensional position vector @xmath78 and @xmath11 with the spring constant reveals that this is precisely the euclidean action for the simple harmonic oscillator . alternatively the action may be viewed as that of a massive scalar field upon identifying @xmath11 with the mass parameter . thus it is possible to introduce a mass term into the state sum model if the mass parameter is treated as an element of the lie algebra @xmath79 . the corresponding matrices @xmath14 furnish an @xmath2-dimensional representation of the abelian group of strictly positive numbers under multiplication , as is the case in . in this way it is possible to include a mass term in the state sum model on the circle while maintaining triangulation independence . in this section , we compute the zeta function regularised partition function of the continuum theory for the gauge group @xmath49 , and show that it is equal to the result from the state sum model . zeta function regularisation is a method of regularising divergent products . it can be used to define the determinant of operators on infinite dimensional spaces , i.e. differential operators . the motivating observation is the following : let @xmath80 be a hermitian , strictly positive operator in a finite - dimensional hilbert space with no eigenvalues that are zero . the zeta function @xmath81 of @xmath80 is defined for @xmath82 by @xmath83 where @xmath84 are the eigenvalues of @xmath80 . as @xmath80 has a finite number of positive eigenvalues , @xmath81 is well defined and holomorphic in @xmath85 . an elementary computation shows that @xmath86 the point of is that the expression on the right hand side may , under certain circumstances , be taken as a definition of @xmath87 even when the hilbert space is infinite dimensional . we require the spectrum of @xmath80 to be discrete , and the sum in must converge for sufficiently large @xmath88 to define @xmath81 as a function that can be analytically continued to @xmath89 . the analytic continuation in @xmath85 provides a prescription for regularising the divergent product @xmath90 . this is useful in quantum field theory because one can use zeta function regularisation to define the partition function of certain theories . so for a minimally coupled scalar field theory , we may define @xmath91 where the square root is the positive square root . the differential operator @xmath80 gives the classical action in the exponent . in the case of a real scalar field minimally coupled to an @xmath1 gauge field on the circle , we have @xmath92 which gives @xmath93 . in order to compute @xmath87 , we first need to know the eigenvalues of @xmath80 . we will take the gauge group to be @xmath49 , so that @xmath94 . using the gauge freedom , we may take @xmath11 to be a constant which we denote by @xmath95 , and by a further gauge transformation we may take @xmath96 . then the eigenvalue equation is @xmath97 and we impose periodic boundary conditions , @xmath98 . this has linearly independent solutions @xmath99 and @xmath100 , @xmath101 . the eigenvalues are given by @xmath102 the determinant in is defined by @xmath103 with @xmath104 this may be re - written in terms of the hurwitz zeta function , @xmath105 where @xmath106 is defined by @xmath107 the hurwitz zeta function can be analytically continued to remove the pole at @xmath89 . then using 25.11.13 , 25.11.18 and 5.5.3 in @xcite , we have @xmath108 and the partition function is @xmath109 the holonomy is given by @xmath110 , and identifying @xmath111 gives precisely the result from the state sum model . thus the zeta function regularisation and the lattice regularisation are seen to be equivalent . the action for the euclidean harmonic oscillator in @xmath2 spatial dimensions is @xmath112 the corresponding partition function on the circle is calculated in @xcite , @xmath113 where @xmath114 is understood to be the positive square root of @xmath115 . this result is identical to the state sum model after identifying @xmath116 . in this paper , a one dimensional state sum model for a real scalar field on the circle and interval has been constructed . the resulting partition functions are simple functions of the holonomy that are triangulation independent . i have carried out an exact calculation of the partition function in the continuum using zeta function methods , and have obtained results identical to the state sum model for the gauge group @xmath1 . if the gauge group is chosen to be the group of strictly positive real numbers under multiplication , the state sum model on the circle is exactly equal to the path integral for the harmonic oscillator . normally the path integral for the harmonic oscillator is constructed as the limit of a state sum that is not triangulation independent . the model here has the added virtue of triangulation independence , and thus in many ways represents a significant simplification . introduction of a mass term in the most obvious way breaks the triangulation independence of the state sum model . this is in agreement with work by rovelli @xcite . however , a mass term can still be accommodated while maintaining triangulation independence if the mass parameter is treated in the same manner as a gauge field . the results here can be extended to the case of a complex scalar field in a straightforward way . the lorentzian path integrals can be obtained by wick rotation . the most interesting generalisation of this work would be to higher dimensions . we hope that the model presented here may clarify some of the issues that arise in that case . i thank john barrett , jorma louko and sara tavares . atlas collaboration ( georges aad ( freiburg u. ) observation of a new particle in the search for the standard model higgs boson with the atlas detector at the lhc " , phys.lett . b716 ( 2012 ) 1 - 29 http://arxiv.org/abs/1207.7214[arxiv:1207.7214 [ hep - ex ] ] .
this paper is a follow - up to a previous paper on fermions @xcite . a simple state sum model for a scalar field on a triangulated @xmath0-manifold is constructed . the model is independent of the triangulation and gives exactly the same partition function as the continuum functional integral with zeta function regularisation . for a certain choice of gauge group , the state sum model on the circle is equivalent to the path integral for the simple harmonic oscillator .
the ectodermal dysplasias ( eds ) are a heterogenous group of diseases , which have one or more anomalies of the hair , teeth , nails , and sweat glands . several ed syndromes may present in association with midfacial defects , such as cleft lip and palate . siemens touraine syndrome ( omim 305100 ) is the most common type followed by autosomal recessive form and autosomal dominant form . he d is characterized by classical triad of hypotrichosis ( reduction in the amount of hair of scalp and body hair ) , anhidrosis / hypohidrosis ( absence or reduction of sweat glands ) , and hypodontia / anodontia ( congenital absence of teeth ) . we hereby report very rare phenotype ; cleft palate and ankylosis of temporomandibular joint ( tmj ) in an indian boy with he d . an 11-year - old boy visited genetic clinic with a chief complaint of missing teeth since childhood and facial dysmorphism . he was first in birth order of nonconsanguineous couple , delivered at full term with uneventful prenatal and perinatal period . he was found to have ankylosis ( fusion ) of bilateral tmj with posterior cleft palate on oral examination . he was operated by fusion release of the band of right and left tmj ankylosis with tracheostomy at 7 months of age . postoperative spiral computed tomography scan of the face and neck at 7 month of age showed posterior cleft palate [ figure 1a and b ] . patient 's mother noted that he remained warm , especially during the summer and was not able to sweat adequately . the mental development was normal for his age . on examination , at 11 years of age , his weight and height were plotted <3 standard deviation for his age . facial features revealed sparse scalp hair , frontal bossing , scanty eyebrows and eyelashes , hyperpigmentation around the eyes , depressed nasal bridge , prominent lips , bilateral low set ears [ figure 2a ] . eye examination showed dryness of the cornea and decreased tearing . intraoral examination revealed two peg - shaped lower canine and two first upper molar teeth , the other were missing , dry mucous membrane , bifid tongue and posterior cleft palate [ figure 2b ] . vertical dimension of the lower face is reduced , and vermilion border was not present , giving senile look to the child as compared with children of his age . orthopantomogram revealed malformed incisors , impacted maxillary and mandibular teeth , and true partial anodontia [ figure 3 ] . based on the history , oral and cutaneous examination , diagnosis of he d was made . patient was evaluated by dentist and planned for removable partial denture after reshaping the existing teeth with composite . as the patient was growing , parents were instructed to defer the placement of the implant until after the completion of jaw growth and eruption of other permanent teeth . ( a ) coronal reconstruction image ( b ) sagittal section ( a ) extraoral photograph showing characteristic features of ectodermal dysplasia . ( b ) intraoral view shows hypodontia and cleft palate orthopantomogram shows malformed and impacted incisors and molars with true partial anodontia hypohidrotic ectodermal dysplasia is inherited in an x - linked recessive ( 95% ) , autosomal dominant , or autosomal recessive manner and is caused by mutation in the eda , edar , and edaradd gene , respectively . these genes regulate the protein eda a , which forms a signal interaction between ectoderm and mesoderm . mutation in this gene results in defective eda a and hence impairs normal development of hair , sweat gland , and teeth . in our case , clinical diagnosis of he d was made based on the history of inability to sweat and hyperthermia , hypodontia , facial , and cutaneous features . children can experience repeated episodes of hyperpyrexia and heat intolerance , which remain unexplained until the disorder is diagnosed . the interesting features in the present case were presence of tmj ankylosis and cleft palate . ankylosis means fusion of the bones forming the joint and caused by poorly - healing severe trauma or infection or congenitally . it was present congenitally along with a cleft palate in our case . in our literature review , the association of cleft palate with ed is known in the literature , but with only few cases reported so far . more et al . did retrospective study of 19 cases of ed and found 94.74% had partial anodontia , 84.21% had conical shaped teeth , 05.26% had complete anodontia , 100% had thin alveolar bone ; and in one case ( 05.26% ) cleft lip and cleft palate . the various syndromes which are associated with ed are rapp - hodgkin syndrome , strandberg - ronchese 's syndrome , rosseli - gulienetti syndrome , odonto - onycho - dermal dysplasia syndrome . major differential diagnosis of he d includes margarita island type of ed , ectrodactyly ectodermal dysplasia cleft ( eec ) syndrome ( ectrodactyly - ed - cleftlip / cleft palate ) and hidrotic ed ( clouston type ) . in margarita island type of ed , males and females are affected equally and characterized by cleft lip and palate , scanty eyebrows and eyelashes , sparse scalp hair , protruding ears , hypodontia , and partial syndactyly of the fingers and toes . eec syndrome is characterized by ectrodactyly ( absence of all or a portion of one or more fingers and/or toes ) , cleft lip / cleft palate , hypodontia , nail dysplasia , dry skin fine , sparse , light scalp hair and eyebrows , absent eyelashes . hidrotic ed is characterized by abnormalities involving the nails , hair , skin , and/or teeth with normal sweating . hypohidrotic ectodermal dysplasia can be associated with immunodeficiency and hence immunoglobulin levels and t - cell count is required . the treatment of he d is a coordinated effort of a multidisciplinary team including pediatricians , dermatologists , dental specialists , otolaryngologists , geneticist , and allergists . it is recommended that children with he d should be live in a cool climate . preventive and protective measures should be advised including avoidance of physical exertion , protection from high temperatures , and excessive fluid intake during summer , cooling by water such as the use of cool clothes and sponge baths . reports suggested that children with he d usually suffer from poor psychological and physiological development . they are more likely to remain unaccepted and rejected by peers thus become more aggressive and may experience mental health problems in the adulthood . therefore , successful dental treatment is required to assist the patient both physically and psychologically . prosthodontic treatment commenced at an early age depends on the patient 's age , the pattern of dysplasia , morphology of the alveolar ridge , and number and morphology of existing teeth . treatment includes the use of removable prosthesis during the early stages of growth and when the patient growth is completed , a more stable and fixed prosthesis and of implant can be considered . it was suggested that cephalometric analysis has a favorable effect on the growth of maxilla and mandible following the placement of dentures . future trial of recombinant eda - a1 administration is going on to correct the features of xlhed . prenatal diagnosis can be performed using mutation analysis by chorionic villus sampling at 1112 weeks of pregnancy or indirect prenatal diagnosis may be performed by linkage analysis . in conclusion , an early diagnosis of he d and dental treatment is an essential part of the management because the psychological factor is always there in the absence of teeth thus dentures will give a psychological boost to the self - image of the child .
the ectodermal dysplasias are a heterogenous group of diseases , which have one or more anomalies of the hair , teeth , nails , and sweat glands . hypohidrotic ectodermal dysplasia ( he d ) is the most common type and is usually transmitted as an x - linked recessive trait . it is characterized by classical triad of hypotrichosis , anhidrosis / hypohidrosis , and hypodontia / anodontia . here , we describe an indian boy affected with he d and rare features including ankylosis of temporomandibular joint and cleft palate .
currently , resin composites are more often used for direct posterior teeth restorations since many advances were made in adhesion and adhesives long - term performances . adhesives are necessary to prevent leakage on resin composite restorations while dental composites are not able to bond to dental tissues . however , clinical microleakage remains the major cause for composite restorations failures implying postoperative sensibility , margin colorations , secondary decay , or pulpal inflammation [ 15 ] . [ 68 ] : the etch and rinse ( er ) adhesive systems ( in three or two clinical steps ) , the self - etch ( se ) adhesive systems ( in two or one clinical step(s ) ) , and the glass ionomer adhesives [ 69 ] . in their in vitro studies , therefore , results from thermocycling experiments have already pointed statistical differences between the er adhesion strategy and the se adhesion strategy [ 19 , 2527 ] . therefore , the purpose of this study was to evaluate bonding performance of different dental adhesives after thermocycling : 2 er adhesives ( scotchbond multipurpose , sbmp3 m espe ag , seefeld , germany a 3-step er adhesive and adper scotchbond 1 t , sb1 3 m espe ag , seefeld , germany a 2-step er adhesive ) and 2 se adhesives ( adhese , adse ivoclar vivadent ag , schaan , liechtenstein a 2-step se adhesive and adhese one , adse-1ivoclar vivadent ag , schaan , liechtenstein a 1-step adhesive ) were evaluated according to the microleakage that was observed . the teeth were stored in a refrigerated saline solution for a maximum of 3 months as recommended by the iso norms ( iso . all the cavities ( n = 40 ) were rectangular , standardized for dimensions and shape ( h w l = 2 mm 2 mm 3 mm ) and were prepared with a cylindrical diamond bur ( diameter = 0.9 mm ) at the coronal - radicular junction : the margins were butt - jointed , half in the enamel and half in the root dentin . after that , the apices were fixed in an autopolymerizing resin ( paladur , heraeus - kulzer gmbh & co. kg , hanau , germany ) . the forty cavities were randomly assigned in 4 groups according to tested adhesive systems ( table 1 ) : scotchbond multipurpose ( sbmp ) ( 3 m espe ag , dental products , seefeld , germany ) , a 3-step etch and rinse ( er ) adhesive system ; adper scotchbond 1 t ( sb1 ) ( 3 m espe ag , dental products , seefeld , germany ) , a 2-step etch and rinse ( er ) adhesive system ; adhse ( adse ) ( ivoclar vivadent ag , schaan , liechtenstein ) , a 2-step self - etch ( se ) adhesive system ; adhse one ( adse-1 ) ( ivoclar vivadent ag , schaan , liechtenstein ) , a 1-step self - etch ( se ) adhesive system . all the tested adhesives were used according to the manufacturer 's instructions . immediately after bonding procedures , the cavities were filled with two oblique increments of a microhybrid composite ( z100 , 3 m espe ag , dental products , seefeld , germany ) . the photopolymerization was carried out for all materials with a halogen lamp ( xl 3000 , 3 m espe ag , dental products , seefeld , germany ) . composite restorations were polished by means of diamond drills and disks ( hawe neos dental , bioggio , switzerland ) . after that , all the specimens were immersed in a saline solution for twelve weeks ( in a refrigerator at 5c ) . thereafter , the teeth were thermocycled for 800 cycles ( 5c55c ) for 22 hours . after thermocycling , the teeth were immersed in a 50% silver nitrate solution ( for 6 hours ) and in a 25% vitamin c solution for 10 minutes ( ph about 2 ) [ 25 , 26 ] . after immersion , three grooves ( 3 mm depth , 1 mm width ) were drilled with a diamond bur in each restoration to obtain four surfaces of observation . the interfaces that occurred between the teeth and the filling was described in our previous studies [ 25 , 26 ] . briefly , the cylindrical diamond drill ( 0.9 mm diameter ) was placed perpendicular to the composite restoration . three grooves 3 mm deep and 1 mm wide were cut on each restoration : one at the mesial margin , one at the distal margin , and one right in the middle of the filling ( figure 1 ) . these preparations yielded four evaluating surfaces for each composite restoration ( figure 2 ) , for a total of 160 viewing surfaces for all tested adhesives . each surface allowed one observation in enamel and one in dentin ( lecture areas ) , for a total of 320 observations ( 160 in enamel and 160 in dentin ) . each section was examined by twofold magnification by means of an optic microscope ( carl zeiss , sas , oberkochen , germany ) . arbitrarily , the evaluation of leakage was made with a 6-point severity scale ( figure 3 , table 2 ) . we have postulated that higher scores of microleakage ( scores 3 , 4 , and 5 ) after thermocycling would be responsible for clinical failure of the bonding ( figure 4 ) . microleakage scores were analyzed by means of generalized linear mixed models ( glmms ) assuming an ordinal logistic link function . covariates in the model were ( 1 ) adhesive systems and ( 2 ) interface ( enamel or dentin ) . all the results were considered to be significant at the 5% critical level ( p < 0.05 ) . statistical calculations were made using the sas 9.1 ( version 8.2 for windows ) package . microleakage mean score calculation for each tested adhesive system was analyzed by statistical model , which takes repeated evaluations into account ( 4 observations for each interface , enamel , or dentin ) . therefore , all the observed scores of microleakage for each adhesive at enamel or at dentin interface are not displayed . the mean scores of microleakage for all tested adhesive systems are shown in table 3 . in our study , sbmp was significantly different from other adhesives : sbmp has shown a lower mean score of microleakage ( 0.30 0.49 ) than other tested adhesives ( p = 0.0007 for sb-1 and p < 0.0001 for the other tested adhesives ) . table 4 reports the statistical comparison between the mean scores of microleakage of the 4 tested adhesives . as seen in table 4 , there was no statistical difference between sb1 and adse ( p = 0.0799 ) , neither between sb1 and adse-1 ( p = 0.072 ) nor between adse and adse-1 ( p = 0.96 ) . table 5 shows the mean scores of microleakage for the 4 tested adhesives at enamel and dentin interfaces . for adse and adse-1 , the mean scores of microleakage were significantly lower at dentin than at enamel interfaces . for the past few years , composite has become current restorative material and today it often replaces amalgam restorations in posterior teeth [ 2831 ] . therefore , the use of an adhesive system is always required . as result of numerous advances in adhesive technology and adhesion knowledge , there are many adhesive systems available on the market . to avoid confusing and incorrect uses of the adhesives , professor bart van meerbeek has proposed a classification according to different adhesion strategies and adhesives : the etch and rinse ( er ) adhesive systems , the self - etch ( se ) adhesive systems , and the glass ionomer adhesive systems [ 6 , 7 , 32 ] . the er adhesives always involve the use of phosphoric acid , which permits demineralization of the dental tissues and , after rinsing , a complete elimination of the smear layer . therefore , in the course of the er adhesion strategy , the adhesive resin ( bonding ) is applied in a different clinical step : the demineralization and the hybridization of dental substrate appear consecutively . on the contrary , with the se adhesives the demineralization and the impregnation of the adhesive into the enamel - dentin support appear simultaneously . the demineralization process results from the acidic monomers , which are components of the adhesive system . there are currently 4 different types of se adhesives , which are indexed according to their ph value : the ultramild se ( ph about 2.5 ) , the mild se ( ph about 2 ) , the intermediary strong se ( ph about 1.5 ) , and the strong se ( ph < 1 ) [ 68 , 32 ] . on the enamel , for both er and se adhesive systems , bonding to the tissue is essentially micromechanical . on the dentin , for the er adhesives , the mechanisms of adhesion are mainly micro - mechanical because the phosphoric acid is a very strong acid ( ph about 0.5 ) . phosphoric acid completely dissolves the mineral and so , the collagen fibers are totally exposed after etching . for the se adhesives , the adhesion to the dentin is both micro - mechanical and chemical [ 68 ] : the self - etch monomers are often less acidic than phosphoric acid and then some minerals remain attached to the collagen fibers , permitting chemical links between dental substrate and functional groups of the adhesive monomers . laboratory experiments have permitted comparison between different bonding materials and have pointed statistical differences between different adhesive systems [ 1024 ] . currently , a lot of studies and reviews agree about the best performances of the er adhesive systems at the enamel and also at the dentin interface for some 3-step adhesives [ 11 , 16 , 19 , 3237 ] . concerning dentin interface , several authors admit that some se adhesives , in particular mild and ultra - mild , are able to create chemical bonds with hydroxyapatite crystals within the dentinal tissue [ 7 , 8 , 32 , 3640 ] . nevertheless , some authors suggest that these mild and ultra - mild se adhesives have poor adhesion capacity to the enamel tissue : so , they recommend the use of phosphoric acid on the enamel surface before applying the se adhesive [ 32 , 34 , 37 , 4143 ] . currently , in vitro microleakage [ 11 , 19 ] and mechanical tests [ 16 , 35 ] often show the superiority of the 3-step er adhesives . for several authors , these adhesive systems are always the gold standard [ 6 , 7 , 32 , 36 , 37 , 44 ] , in particular the optibond fl ( kerr , european union representative , scafati ( sa ) , italy ) [ 5 , 7 , 45 ] and/or the scotchbond multi - purpose plus ( sbmp ) ( 3 m espe ag , seefeld , germany ) [ 5 , 36 , 44 ] . the results of our study are in agreement with the data from the literature : in our experiment , sbmp has shown the best results in terms of microleakage . nevertheless , for some authors , 2-step mild and ultra - mild se adhesives can give comparable results than those obtained by some 2-step er adhesives and also , by some 3-step er adhesive systems [ 610 , 32 , 34 , 36 , 37 ] . in fact , our results have shown that adse ( 2-step se ) and sb1 ( 2-step er ) have statistically comparable mean scores of microleakage . concerning the 1-step se adhesives , some in vitro studies have shown their poor performances [ 7 , 34 , 46 ] . our results do not confirm this fact : there is no statistical difference between the mean scores of microleakage of adse ( a 2-step se ) and its simplified clinical version , adse-1 ( a 1-step se ) . in addition , the mean scores of microleakage of these two mild se adhesives ( ph about 2 ) are lower at the dentin interface than at the enamel interface . these observations agree with data from the literature : adse and adse-1 are not efficient to create a sufficient micro - mechanical retention at the enamel surface [ 6 , 7 , 16 , 34 , 43 ] . nevertheless , at the dentin surface , these mild se adhesives are able to create a partial demineralization of this tissue to allow a micro - mechanical adhesion [ 6 , 7 ] . in addition , some functional monomers of these se adhesives might form chemical bonds with the calcium of the residual hydroxyapatite crystals linked to the collagen fibers [ 7 , 32 , 3840 ] . the chemical bonds between adse functional monomers have not been clearly identified yet , but this adhesive has given good results in our study , like in the study of bradna et al . . in this study , confirming previous studies about marginal microleakage of the er adhesive systems , sbmp , a 3-step er adhesive , has significantly less microleakage comparing to other adhesive systems and can be considered like a reference adhesive . the parameters of this experiment ( hydrolysis and thermocycling ) have shown the good in vitro behaviour of sbmp . in fact , this adhesive has been widely used for many years and their performances have seemed good . the 2-step er adhesive that was tested in our study has shown a significantly greater mean score of microleakage than the tested 3-step er adhesive system , but all the tested adhesives showed minimal leakage . in the limits of our study , nevertheless , we suggest these mild se adhesives can be used when the margins of the cavity are located on dentin and/or using phosphoric acid only on the enamel margin in order to optimize micro - mechanical interlocking .
our experiment evaluated the microleakage in resin composite restorations bonded to dental tissues with different adhesive systems . 40 class v cavities were prepared on the facial and lingual surfaces of each tooth with coronal margins in enamel and apical margins in cementum ( root dentin ) . the teeth were restored with z100 resin composite bonded with different adhesive systems : scotchbond multipurpose ( sbmp ) , a 3-step etch and rinse adhesive , adper scotchbond 1 xt ( sb1 ) , a 2-step etch and rinse adhesive , adhese one ( adse-1 ) , a 1-step self - etch adhesive , and adhese ( adse ) , a 2-step self - etch adhesive . teeth were thermocycled and immersed in 50% silver nitrate solution . when both interfaces were considered , sbmp has exhibited significantly less microleakage than other adhesive systems ( resp . , for sb1 , adse-1 and adse , p = 0.0007 , p < 0.0001 and p < 0.0001 ) . when enamel and dentin interfaces were evaluated separately , ( 1 ) for the self - etch adhesives , microleakage was found greater at enamel than at dentin interfaces ( for adse , p = 0.024 and for adse-1 , p < 0.0001 ) ; ( 2 ) for the etch and rinse adhesive systems , there was no significant difference between enamel and dentin interfaces ; ( 3 ) sbmp was found significantly better than other adhesives both at enamel and dentin interfaces . in our experiment etch and rinse adhesives remain better than self - etch adhesives at enamel interface . in addition , there was no statistical difference between 1-step ( adse-1 ) and 2-step ( adse ) self - etch adhesives .
Huckabee blames GOP for allowing Akin’s ‘legitimate rape’ comment to sink campaign By Scott Kaufman Monday, July 7, 2014 11:37 EDT In the forward to former Senate candidate Todd Akin’s new book, former Arkansas governor and potential 2016 presidential candidate Mike Huckabee defends Akin’s “legitimate rape” comment. “I expected Democrats to pounce on Todd,” Huckabee wrote, for a comment that women don’t become pregnant in cases of “legitimate rape.” “But I was disheartened and outraged when Republicans circled the wagons,” he continued, “not to support Todd and help him overcome an obstacle but instead as a firing squad pointed at the congressman.” Huckabee further claimed that the author of Firing Back: Taking on the Party Bosses and Media Elite to Protect Our Faith and Freedom is just one of many “social conservatives” who have been attacked by “party bosses, partisan power brokers and the entrenched GOP establishment.” “I’m deeply offended by this infighting within the Republican Party,” he wrote, “because it is so destructive to the country we care so deeply about.” Oliver North also contributed a glowing review of Akin and his book, writing that he admires “Todd’s stand for the sanctity of life” and “his steadfast resolve against an onslaught of media bullies and party bosses,” which he characterized as “the stuff of legend.” According to Right Wing Watch, Akin’s publisher — World Net Daily’s Joseph Farah — said that the “legitimate rape” comment “represents in its entirety one of the best articulations of the life ethic. There’s simply nothing in there that is factually wrong or offensive — unless you are looking to be offended by something.” [Image via Gage Skidmore, Creative Commons licensed] ||||| Data crawled on behalf of Internet Memory Foundation . This data is currently not publicly accessible.from Wikipedia The Internet Memory Foundation (formerly the European Archive Foundation) is a non profit foundation whose purpose is archiving web content, it supports projects and research which include the preservation and protection of multimedia content. Its archives form a digital library of cultural content. ||||| Todd Akin takes it back. He’s not sorry. Text Size - + reset Two years after the Missouri Republican’s comments on rape, pregnancy and abortion doomed his campaign and fueled a “war on women” message that carried Democrats to victory in the Senate, one of the few regrets he mentions in a new book is the decision to air a campaign ad apologizing for his remarks. “By asking the public at large for forgiveness,” Akin writes, “I was validating the willful misinterpretation of what I had said.” (PHOTOS: 5 controversial Todd Akin quotes) And when it comes to his infamous line about rape and pregnancy, that “the female body has ways to try to shut that whole thing down,” he writes defiantly: “My comment about a woman’s body shutting the pregnancy down was directed to the impact of stress on fertilization. This is something fertility doctors debate and discuss,” Akin writes. “Doubt me? Google ‘stress and infertility,’ and you will find a library of research on the subject.” “Firing Back: Taking on the Party Bosses and Media Elite to Protect Our Faith and Freedom” hits bookshelves July 15. An advance copy was provided to POLITICO by a source involved with the book. Akin argues that he could have defeated Sen. Claire McCaskill in Missouri, despite his comments, if it weren’t for the piling on from both liberals and conservatives. He compares his situation sympathetically to that of George Allen, who lost a Senate race in Virginia after calling a liberal tracker a racial slur. And he accuses liberals of hypocrisy for asking Bill Clinton to headline the Democratic National Convention. (From last year: Akin says he regrets rape comments) The forward is written by former Arkansas Gov. Mike Huckabee, but few other conservatives are likely to cheer Akin’s return to the national stage in the final months of a campaign season Republicans vowed would not be shaped by the mistakes of 2012, when comments about rape and women’s issues derailed their hopes of retaking the Senate. Akin isn’t concerned. Here are some key takeaways from his book: Defends comments on rape Akin offers no apologies for his “legitimate rape” comment and blames liberal news media for how it was received. The liberal opposition research super PAC American Bridge dug up the video and sent it to Talking Points Memo, described as one of the “well-funded, left-leaning blogs.” Talking Points Memo posted the footage and started a firestorm. Akin systematically defends every phrase in his response to whether abortion in the case of rape should be legal. “Taking my comments in order: When a woman claims to have been raped, the police determine if the evidence supports the legal definition of ‘rape.’ Is it a legitimate claim of rape or an excuse to avoid an unwanted pregnancy?” (From the POLITICO archives: Akin: 'Legitimate rape' victims rarely get pregnant) “My comment about a woman’s body shutting the pregnancy down was directed to the impact of stress on fertilization. This is something fertility doctors debate and discuss. Doubt me? Google ‘stress and infertility,’ and you will find a library of research on the subject.” To further make his case, Akin says he was hesitant to appear on a local Fox show hosted by Charles Jaco, where he made those comments, because the “hard-bitten liberal” could make the interview a “high-risk venture.” The fact that Jaco didn’t immediately pounce on his comments was because he heard them “in context with the various qualifiers.” Akin later says during his time as a state legislator, he wished he could have done more to “end this evil,” referring to abortion, which in his view “easily trumps slavery as the greatest moral evil in American history.” As Akin makes the case that he has “zero sympathy” for anyone who commits rape, he tries to illustrate his commitment by pointing to President Bill Clinton. Akin writes that if he had been in Congress in 1998 he would have voted to impeach Clinton. The investigation started, according to Akin, with allegations of sexual assault of Paula Jones, which then led investigators to learn about his affair with intern Monica Lewinsky. The impeachment involved Lewinsky, not sexual assault. Akin writes that Republican presidential candidate Mitt Romney should have defended him by using Clinton’s indiscretions and alleged comment that one woman “put some ice on that” just as Clinton was set to serve as a keynote speaker at the Democratic National Convention. In 2012, Romney denounced Akin’s comments and urged him to drop out of the race. What Akin believes Romney should have said when asked about the “legitimate rape” comments: “[Bill Clinton] is giving the keynote speech at the Democratic convention in two weeks, and you want me to denounce a decent, God-fearing man for his inelegant comments about rape? No, not happening, and if the truth hurts, put some ice on it.”
– First Todd Akin said "legitimate rape" victims rarely get pregnant. Then the Missouri rep apologized for the rape comment in a commercial for his 2012 Senate run and the world moved on (but not before opponent Claire McCaskill soundly defeated him). Now he’s back with a new book and a new (old) outlook: that he was scientifically accurate in his initial assessment of rape, according to Politico. "My comment about a woman’s body shutting the pregnancy down was directed to the impact of stress of fertilization," he writes in Firing Back: Taking on the Party Bosses and Media Elite to Protect Our Faith and Freedom. "This is something fertility doctors debate and discuss. Doubt me? Google 'stress and infertility,' and you will find a library of research on the subject." And he says apologizing for the initial comment is one of his few regrets: "By asking the public at large for forgiveness, I was validating the willful misinterpretation of what I had said." Former Arkansas governor Mike Huckabee penned the foreword to Akin's book, scheduled to hit shelves July 15, and calls out Republicans who "circled the wagons," according to Raw Story, "not to support Todd and help him overcome an obstacle but instead as a firing squad pointed at the congressman."
When astronauts looked out the window of the International Space Station in early July, they noticed a swirling mass of clouds over the Atlantic Ocean, which turned out to be the beginning of tropical storm Arthur. VIDEO: Why Are Hurricanes with Female Names More Deadly? Above, a National Weather Service satellite image from Sept. 30 shows the temperature of Earth's surface as a cold front moving across the plains brought severe thunderstorms to areas in South Dakota and Nebraska. VIDEO: The Difference Between A Typhoon And A Hurricane A lava flow on the Big Island of Hawaii brought 2,000-degree lava across a road in the town of Pahoa. Meet the Guy Who Went Into a Volcano The Ocean Atlas underwater sculpture, an 18-foot (5.4 meters), 60-ton statue, was deployed off the coast of Nassau in the Bahamas. PHOTOS: Underwater Sculpture Museum Forms Coral Reef Astronauts aboard the International Space Station took this photograph of Florida in October 2014. Dim lights of the Florida Keys extend the arc of the Atlantic coast to the corner of the image. The small cluster of lights far offshore is Freeport on Grand Bahama Island (at right). The faint blue areas throughout the image are clouds lit by moonlight. The U.S. Environmental Protection Agency maintains these controlled growth chambers in Corvallis, Ore. They enable researchers to study the effects of air pollution, heavy metals, and toxic substances on plant life. VIDEO: How Can Something Be a Plant and an Animal? Herbert is a volcanic island located in the Aleutian chain off of Alaska. A symmetrical stratovolcano stands in its center, rising 4,200 feet (1,280 meters) above the North Pacific Ocean. The entire island is just 6 miles (10 kilometers) across. NEWS: Alaska's Pavlof Volcano Belches Out Ash Cloud A break in the clouds on Oct. 29, 2014, allowed scientists the opportunity to fly over Pine Island Glacier—one of Antarctica’s most rapidly changing areas. PHOTOS: Global Warming Right Before Your Eyes We already know that rising temperatures can disrupt the migratory patterns of birds. But a new study by Oregon State University researchers reveals that changes in rainfall caused by climate change are causing drastic declines in populations of birds such as the rufous hummingbird, pictured above. Top 10 Tricks for Pollinators Check out the 10 most striking photos of Planet Earth that we've come across all year. Above, fighter jets capture images of fire clouds produced by California wildfires that can spread smoke and pollutants across large areas. Ironically, the clouds can trigger thunderstorms that help extinguish wildfires. VIDEO: Should We Control Wildfires? Some of them look like big pillows or lines across the sky, while others may remind you of Winston Churchill’s profile. But at any given moment, about two-thirds of the Earth’s surface usually is covered by clouds, according to a NASA study based upon satellite observations. For a long time, scientists have been trying to figure out exactly how that cloud cover might affect the climate change process — or how it might be altered by global warming. Photos: Know Your Cloud Types So that you can visualize just how cloudy our planet is, NASA scientists have created this very cool global cloud fraction map. It’s based upon data collected between 2002 and 2015 by the Moderate Resolution Imaging Spectroradiometer, or MODIS, an instrument on NASA’s 13-year-old Aqua satellite, which is studying the Earth’s water cycle. As you can see from the image, there are three bands where the skies are most likely to be overcast — a narrow strip near the Earth’s equator and two wider swaths in the mid-latitudes, 60 degrees north and south of the equator. The equatorial cloud band is related to Hadley cells, which are low-attitude circulation patterns that cause warm, moist air to rise and cool in that area, which causes the water vapor to condense and form clouds. (That’s also why the area has a lot of thunderstorms.) NEWS: How Do Clouds Affect Earth’s Climate? The middle latitude bands, in contrast, where the edges of polar and mid-latitude Ferrel cells collide and push air upward, (For more info, here’s a primer on cloud formation from the University Corporation for Atmospheric Research. Clouds’ effect on climate change — and vice-versa — long has been a matter of debate among climate scientists, as this National Science Foundation report details. Back in 1997, in fact, the Intergovernmental Panel on Climate Change described clouds as “the largest source of uncertainty” in climate change predictions. Different types of clouds have different effects. Stratus clouds, for example, block sunlight from reaching the Earth, and actually tend to have a cooling effect, while wispy, feathery cirrus clouds tend to let sunlight through but trap reflected heat from the Earth’s surface, magnifying warming. Overall, the net effect of clouds has been cooling, and some scientists have held out hope that the cloud cover will respond to feedback and shift to mitigate much of the predicted rise in global temperatures. But recent research, such as this 2009 study by University of Miami scientists and this 2014 study by University of Paris researchers, suggests the opposite. In that scenario, climate change will alter the cloud cover, thinning it in a way that actually will exacerbate the warming effect. ||||| I’ve seen a lot of images of our fair blue world, but this one is unique and (somewhat more than metaphorically) breath-taking: a map of Earth showing its average cloudiness. Photo by NASA Earth Observatory image by Jesse Allen and Kevin Ward, using data provided by the MODIS Atmosphere Science Team, NASA Goddard Space Flight Center That gorgeous picture was made using data from the Aqua satellite, which observes the Earth to measure its water cycle. That includes keeping an eye on air moisture, precipitation, ice (both on land and sea), snow, and, obviously, clouds. Advertisement This image was made by taking more than a decade’s worth of observations—from July 2002 to April 2015—and getting the average value for the cloud cover at each location on the planet. These were then translated into colors: dark blue for no cloud cover, white for cloudy all the time, and shades of blue in between. A lot jumps out even at a glance. The Sahara and Middle East are obvious dry spots, as is Australia and western Chile. But note Antarctica: A lot of people don’t know just how dry it is there along its interior. It’s not even completely ice covered; there are dry valleys there with no snow on them at all. Phil Plait Phil Plait writes Slate’s Bad Astronomy blog and is an astronomer, public speaker, science evangelizer, and author of Death From the Skies! What struck me most is the wet/dry band west of South America along the Equator, as well as the obvious cloudy bands across high latitudes in the north and south. These betray large-scale circulation patterns in the atmosphere. Moist cool air from low-latitudes (again, both north and south) flow toward the equator, where they warm and rise, forming clouds. At the higher latitudes, clouds form at the boundary of polar air circulation regions. Note that deserts are common too around ±30° latitude; air descends there, inhibiting cloud formation, encouraging desertification. The sharp band in the Pacific is due to ocean circulation patterns redistributing heat in the water. This pattern changes on different time scales; one is over a few years and is called the El Niño Southern Oscillation, or ENSO, and the other on a decadal scale and is the Pacific Decadal Oscillation, or PDO. These affect climate all over the planet. Speaking of which, one other thing that you can see from this map is how interconnected our planet’s clouds are. What happens at one latitude can profoundly affect what happens at another. The ENSO can mean the difference between drought and flooding for locations scattered across Earth. There is no such thing as an isolated location. NASA’s fleet of Earth-observing satellites gives us critical coverage of the various natural forces shaping the environment of the entire world, information we desperately need to understand our own effect. And our effect is profound. What will stop them is for the public to understand better just what science does, and just what scientists think. Ninety-seven percent of climate scientists agree that global warming is real, and humans are responsible. ||||| NASA map shows thirteen years of cloud cover Find Your Forecast Search by city or full postcode Daniel Martins Digital Reporter Tuesday, May 12, 2015, 10:13 GMT - Wondering where the cloudiest or most clear-skied places on Earth are? NASA has you covered. What you're looking at in the image below is an image of the Earth collected by NASA's Aqua satellite, using its Moderate Resolution Imaging Spectroradiometer (MODIS) instrument, representing average cloud cover (the darker the colour, the less cloudy it is). While MODIS can take daily cloud coverage images, the picture below is an average of 13 years of cloud cover data, from July 2002 to April 2015 (click on it for a larger look). It's easy to see where all the deserts are. Africa is dominated by darker hues, even beyond the legendary Sahara, as well as the Middle East and Australia. In the Americas, the U.S. southwestern states, including drought-stricken California, stand out with their darker blues, while in South America, the near-zero cloud cover of Chile's Atacama Desert is a stark contrast to the whiter hues of the rest of the continent. Then there's the rain forests. While the map is about cloud cover, not precipitation, it's pretty easy to see why the jungles of South America, Central Africa and Indonesia are so lush and green. As amazing as it looks, NASA had a couple of caveats when it released the image late last week. "Note because the map is simply an average of all of the available cloud observations from Aqua, it does not illustrate daily or seasonal variations in the distribution of clouds," the agency says. "Nor does the map offer insight into the altitude of clouds or the presence or absence of multiple layers of clouds (though such datasets are available from MODIS and other NASA sensors). Instead it simply offers a top-down view that shows where MODIS sees clouds versus clear sky." NASA also notes the reflectivity of the surface beneath the cloud can affect the MODIS instrument's efficacy, so different techniques are used to calculate the cloud cover depending on whether the landscape below is a desert, coast, forest or even ocean. "For instance, the MODIS is better at detecting clouds over the dark surfaces of oceans and forests, than the bright surfaces of ice," NASA says. "Likewise, thin cirrus clouds are more difficult for the sensor to detect than optically thick cumulus clouds." SOURCE: NASA Follow Daniel Martins on Twitter ||||| Clouds also tend to form in abundance in the middle latitudes 60 degrees north and south of the equator. This is where the edges of polar and mid-latitude (or Ferrel) circulation cells collide and push air upward, fueling the formation of the large-scale frontal systems that dominate weather patterns in the mid-latitudes. While clouds tend to form where air rises as part of atmospheric circulation patterns, descending air inhibits cloud formation. Since air descends between about 15 and 30 degrees north and south of the equator, clouds are rare and deserts are common at this latitude. There are three broad bands where Earth’s skies are most likely to be cloudy: a narrow strip near the equator and two wider strips in the mid-latitudes. The band near the equator is a function of the large scale circulation patterns—or Hadley cells —present in the tropics. Hadley cells are defined by cool air sinking near the 30 degree latitude line north and south of the equator and warm air rising near the equator where winds from separate Hadley cells converge. (The diagram here illustrates where Hadley cells are located and how they behave.) As warm, moist air converges at lower altitudes near the equator, it rises and cools and therefore can hold less moisture. This causes water vapor to condense into cloud particles and produces a dependable band of thunderstorms in an area known as the Inter Tropical Convergence Zone (ITCZ). Earth’s cloudy nature is unmistakable in this global cloud fraction map, based on data collected by the Moderate Resolution Imaging Spectroradiometer (MODIS) on the Aqua satellite. While MODIS collects enough data to make a new global map of cloudiness every day, this version of the map shows an average of all of the satellite’s cloud observations between July 2002 and April 2015. Colors range from dark blue (no clouds) to light blue (some clouds) to white (frequent clouds). Ocean currents govern the second pattern visible in the cloudiness map: the tendency for clouds to form off the west coasts of continents. This pattern is particularly clear off of South America, Africa, and North America. It occurs because the surface water of oceans gets pushed west away from the western edge of continents because of the direction Earth spins on its axis. In a process called upwelling, cooler water from deep in the ocean rises to replace the surface water. Upwelling creates a layer of cool water at the surface, which chills the air immediately above the water. As this moist, marine air cools, water vapor condenses into water droplets, and low clouds form. These lumpy, sheet-like clouds are called marine stratocumulus, the most common cloud type in the world by area. Stratocumulus clouds typically cover about one fifth of Earth’s surface. In some of the less cloudy parts of the world, the influence of other physical processes are visible. For instance, the shape of the landscape can influence where clouds form. Mountain ranges force air currents upward, so rains tend to form on the windward (wind-facing) slopes of the mountain ranges. By the time the air has moved over the top of a range, there is little moisture left. This produces deserts on the lee side of mountains. Examples of deserts caused by rain shadows that are visible in the map above are the Tibetan Plateau (north of the Himalayan Mountains) and Death Valley (east of the Sierra Nevada Range in California). A rain shadow caused by the Andes Mountains contributes to the dryness of the coastal Atacama Desert in South America as well, but several other factors relating to ocean currents and circulation patterns are important. Note because the map is simply an average of all of the available cloud observations from Aqua, it does not illustrate daily or seasonal variations in the distribution of clouds. Nor does the map offer insight into the altitude of clouds or the presence or absence of multiple layers of clouds (though such datasets are available from MODIS and other NASA sensors). Instead it simply offers a top-down view that shows where MODIS sees clouds versus clear sky. Since the reflectivity of the underlying surface can affect how sensitive the MODIS is to clouds, slightly different techniques are used to detect clouds over the ocean, coasts, deserts, and vegetated land surfaces. This can affect cloud detection accuracy in different environments. For instance, the MODIS is better at detecting clouds over the dark surfaces of oceans and forests, than the bright surfaces of ice. Likewise thin cirrus clouds are more difficult for the sensor to detect than optically thick cumulus clouds. NASA Earth Observatory images by Jesse Allen and Kevin Ward, using data provided by the MODIS Atmosphere Science Team, NASA Goddard Space Flight Center. Caption by Adam Voiland, with information from Steve Platnick and Tom Arnold. ||||| This beautiful map shows an average of all of the available cloud observations from the Aqua satellite. The shades of blue represent the cloudiness of our planet. Advertisement The visual is based on data acquired from July 2002 until April 2015, offering a top-down view that shows where the satellite’s Moderate Resolution Imaging Spectroradiometer saw clouds versus clear sky: dark blue represents no clouds, light blues are some clouds, white areas are frequent clouds. According to NASA Earth Observatory: Advertisement One study based on nearly a decade of satellite data estimated that about 67 percent of Earth’s surface is typically covered by clouds. This is especially the case over the oceans, where other research shows less than 10 percent of the sky is completely clear of clouds at any one time. Over land, 30 percent of skies are completely cloud free. Earth’s cloudy nature is unmistakable in this global cloud fraction map, based on data collected by the Moderate Resolution Imaging Spectroradiometer (MODIS) on the Aqua satellite. While MODIS collects enough data to make a new global map of cloudiness every day, this version of the map shows an average of all of the satellite’s cloud observations between July 2002 and April 2015. There are three broad bands where Earth’s skies are most likely to be cloudy: a narrow strip near the equator and two wider strips in the mid-latitudes. [NASA Earth Observatory]
– Blue Marble, yes. Cloudy Blue Marble? Most definitely. The NASA Earth Observatory is out with another compelling image of our planet, one that shows it's a cloudy place. Specifically, about two-thirds of Earth's surface is covered by clouds at any given moment. The map is based on data collected between 2002 and 2015 by a satellite called Aqua, whose mission is to study the planet's water cycle, reports Discovery. Some observations: Where it's cloudiest: "There are three broad bands where Earth’s skies are most likely to be cloudy: a narrow strip near the equator and two wider strips in the mid-latitudes," says NASA. "The band near the equator is a function of the large scale circulation patterns—or Hadley cells—present in the tropics." Much to take in: "A lot jumps out even at a glance," writes Phil Plait at Slate. "The Sahara and Middle East are obvious dry spots, as is Australia and western Chile. But note Antarctica: A lot of people don’t know just how dry it is there along its interior." Deserts: "It's easy to see where all the deserts are," writes Daniel Martins at the Weather Network. "Africa is dominated by darker hues, even beyond the legendary Sahara, as well as the Middle East and Australia. In the Americas, the US southwestern states, including drought-stricken California, stand out with their darker blues, while in South America, the near-zero cloud cover of Chile's Atacama Desert is a stark contrast to the whiter hues of the rest of the continent." Tracking mountains: "On a more local scale, you can see cloud patterns that closely match mountain formations," notes Joseph Stromberg at Vox. "In the US, for instance, clouds regularly form along the ridges of the Rocky Mountains (and to a lesser extent the Appalachians) because of the air masses that get blown eastward and pushed up the mountains. When that happens, they cool, and can't hold as much moisture—so their water vapor condenses to form clouds." But mainly: Science aside, this map is simply a "beautiful visual," notes a post at Gizmodo. In other NASA news, click to read about the strange sounds recorded at the edge of space.
in april 2009 , a 63-year - old woman was admitted to our hospital because of a frontal headache that occurred when she woke up . the thoracic pain was described as continuous , nonconstrictive , not related to breathing , with no irradiation , and which decreased when she laid down . her past medical history was marked by a copd gold ii condition , a chronic left arm oedema of undetermined origin , and an appendicectomy . her current medications included an association of fluticasone and salmeterol as well as tiotropium for the copd . she had been smoking 100 cigarette pack - years , had occasional alcohol consumption , and didnot have any known allergy . the only clinical abnormality was the presence of a murmur on the left supraclavicular area . the first blood test showed an elevation of c - reactive protein at 9.8 mg / dl and a mild normocytic anemia at 11.1 g / dl . the electrocardiogram showed normal sinus rhythm and negative t waves of small amplitude in the second precordial derivation . a computed tomography of the pulmonary artery did not reveal pulmonary embolism but disclosed a circumferential pericardial effusion . the patient was managed as an outpatient and treated with 4 grams of aspirin each day for idiopathic pericarditis . after two weeks of this regimen , the inflammatory syndrome failed to subside , and the controlled transthoracic echocardiogram did not show any improvement of the pericardial effusion . during the course of the following days , the patient developed fatigue and was referred to the consultation of general internal medicine . suspecting giant cell arteritis , fdg - pet was performed because the patient refused the temporal artery biopsy . it revealed striking hypermetabolism of the thoracic and abdominal aortic wall , highly suggestive of large vessel vasculitis ( figure 1 ) . six months after the beginning of the treatment , the fdg - pet didnot show any hypermetabolism in the aortic walls ( figure 1 ) . this case highlights the importance of recognising pericarditis as a possible initial manifestation of giant cell arteritis in patients over 50 years old . it also emphasises the promising role of fdg - pet as a minimally invasive alternative procedure to temporal artery biopsy . fdg - pet can also be used in the followup of patients with giant cell arteritis and seems to identify a subpopulation of patients at risk of developing thoracic aortic dilatation . in the present case , the diagnosis of large vessel vasculitis ( and most probably giant cell arteritis ) has been made based upon clinical grounds , biological markers , and fdg - pet . in spite of the fact that temporal artery biopsy is mandatory to confirm the diagnosis of giant cell arteritis , fdg - pet can be a very useful tool in delineating the diagnostic process .
large vessels vasculitis and more specifically , giant cell arteritis , is characterized by increased inflammatory markers , headaches and altered clinical status . diagnosis is confirmed by biopsy of temporal arteries showing the presence of granuloma and vasculitis . we hereby report the case of a patient presenting initially as pericarditis and revealing large vessel vasculitis using fdg - pet .
SECTION 1. SHORT TITLE; TABLE OF CONTENTS. (a) Short Title.--This Act may be cited as the ``Responsibility to Iraqi Refugees Act of 2007''. (b) Table of Contents.--The table of contents for this Act is as follows: Sec. 1. Short title; table of contents. Sec. 2. Expansion of special immigrant status for certain Iraqis. Sec. 3. Special Coordinator for Iraqi refugees. Sec. 4. Security and related grounds for inadmissibility. Sec. 5. Authorizations of appropriations. SEC. 2. EXPANSION OF SPECIAL IMMIGRANT STATUS FOR CERTAIN IRAQIS. (a) In General.--Notwithstanding any other provision of law, for purposes of the Immigration and Nationality Act (8 U.S.C. 1101 et seq.), subject to subsection (c)(1), the Secretary of Homeland Security may provide an alien described in subsection (b) with the status of a special immigrant under section 101(a)(27) of such Act (8 U.S.C. 1101(a)(27)), if-- (1) the alien, or an agent acting on behalf of the alien, files with the Secretary of Homeland Security a petition under section 204 of such Act (8 U.S.C. 1154) for classification under section 203(b)(4) of such Act (8 U.S.C. 1153(b)(4)); and (2) the alien is otherwise eligible to receive an immigrant visa and is otherwise admissible to the United States for permanent residence, except in determining such admissibility, the grounds for inadmissibility specified in section 212(a)(4) of such Act (8 U.S.C. 1182(a)(4)) shall not apply. (b) Aliens Described.-- (1) Principal aliens.--An alien is described in this subsection if the alien-- (A) is a national of Iraq; (B) worked directly with the United States Government, the United Nations, certified government or United Nations contractor or subcontractor, or United States-based nongovernmental organization for a period of at least one year; and (C) has a not manifestly unfounded fear of persecution, violence, or harm to the alien or the alien's family on account of the work of the alien under subparagraph (B). (2) Spouses and children.--An alien is described in this subsection if the alien is the spouse or child of a principal alien described in paragraph (1), and is following or accompanying to join the principal alien. (3) Presumption.--An alien who is described in subparagraphs (A) and (B) of paragraph (1) shall be presumed to satisfy the requirement described in subparagraph (C) of such paragraph. (c) Numerical Limitations and Benefits.-- (1) In general.--The total number of principal aliens who may be provided special immigrant status under this section shall not exceed 15,000 for each of fiscal years 2008 through 2011. (2) Exclusion from numerical limitations.--Aliens provided special immigrant status under this section shall not be counted against any numerical limitation under sections 201(d), 202(a), or 203(b)(4) of the Immigration and Nationality Act (8 U.S.C. 1151(d), 1152(a), and 1153(b)(4)). (3) Benefits.--Aliens provided special immigrant status under this section shall be eligible for the same resettlement assistance, entitlement programs, and other benefits as refugees admitted under section 207 of the Immigration and Naturalization Act (8 U.S.C. 1157). (d) Protection of Aliens.-- (1) In general.--The Secretary of State, in consultation with the Secretary of Homeland Security, shall provide an alien described in this section who is applying for a special immigrant visa with protection if such Secretaries determine that such alien is in imminent danger. (2) Forms of protection.--Protection required under paragraph (1) may include temporary housing on United States military bases or at provincial reconstruction team offices or the immediate removal from Iraq of such alien. (e) Processing Facilities.-- (1) In general.--Not later than 90 days after the date of the enactment of this Act, the Secretary of State, in consultation with the Secretary of Homeland Security, shall establish not fewer than five processing facilities where aliens described in subsection (b) may apply and interview for admission to the United States as special immigrants and where aliens described in section 6(b) may apply and interview for admission to the United States as refugees. (2) Locations.--The processing facilities required under paragraph (1) shall be established in at least-- (A) two locations in Baghdad; (B) one location in southern Iraq; and (C) two locations in Iraqi Kurdistan. (3) Minimization of security risks.--The processing facilities shall be established so as to minimize to the greatest extent practicable security risks for aliens described in subsection (b) who are applying and interviewing for admission to the United States as special immigrants. (f) Cooperation With Iraqi Government Officials.-- (1) In general.--The Secretary of State and the Secretary of Homeland Security shall seek to cooperate with appropriate officials from the Government of Iraq to-- (A) increase the capacity of the Government of Iraq to issue passports to aliens described in subsection (b); and (B) ensure that aliens described in this section who are issued special immigrant visas are provided with the appropriate series Iraqi passport necessary to enter the United States. (2) Payment of passport fees.--The Secretaries shall pay the costs associated with the issuance of such Iraqi passports. (g) Waiver of Visa Fees.--Neither the Secretary of State nor the Secretary of Homeland may charge an alien described in this section any fee in connection with an application for or issuance of a special immigrant visa. (h) Report.-- (1) In general.--Not later than 90 days after the date of the enactment of this Act, the President shall submit to Congress a report on aliens described in this section who worked directly with the United States Government, the United Nations or other international organizations, certified government or international organization contractors or subcontractors, or international nongovernmental organization as a translator for a period of at least one year. (2) Classified annex.--The report required under paragraph (1) may include a classified annex, containing information relating to personally identifiable information, as necessary, to be used by appropriate United States Government officials for the purpose of processing applications for special immigrant visas under this section. (i) Application of Immigration and Nationality Act Provisions.--The definitions in subsections (a) and (b) of section 101 of the Immigration and Nationality Act (8 U.S.C. 1101) shall apply in the administration of this section. (j) Regulations.--Not later than 90 days after the date of the enactment of this Act, the Secretary of Homeland Security shall promulgate regulations to carry out the provisions of this section, including regulations relating to requirements for background checks. (k) Authorization of Appropriations.--There are authorized to be appropriated such sums as may be necessary to carry out this section. SEC. 3. SPECIAL COORDINATOR FOR IRAQI REFUGEES. (a) In General.--There is established in the Department of State a Special Coordinator for Iraqi Refugees and Internally Displaced Persons. (b) Location.--The Special Coordinator shall be based at the embassy of the United States in Baghdad, Iraq. (c) Duties.--The Special Coordinator shall be responsible for the development and implementation of appropriate policies and programs concerning Iraqi refugees and internally displaced persons, and shall establish an inter-agency task force to coordinate such policies and programs. SEC. 4. COUNTRIES OF SIGNIFICANCE. With respect to each country containing a significant population of displaced Iraqis, including Iraq, Jordan, Syria, Turkey, and Lebanon, the Secretary of State shall-- (1) as appropriate, seek to negotiate a bilateral refugee resettlement agreement for such populations; (2) develop mechanisms to ensure the well-being, safety, and right to work of such populations in their host environments, including the necessary financial, material, and political assistance to support such mechanisms; (3) submit to Congress, not later than 90 days after the date of the enactment of this Act and every 90 days thereafter, a report on the actions taken and progress made under this subsection. SEC. 5. STUDY AND REPORT BY GAO. Not later than one year after the date of the enactment of this Act and annually thereafter, the Comptroller General of the United States shall submit to Congress a report on the adequacy and effectiveness of United States and United Nations programs to protect and assist Iraqi refugees and internally displaced persons. SEC. 6. INCREASE IN NUMERICAL LIMITATIONS. (a) In General.--In addition to the numerical limitations provided for under subsections (a) and (b) of section 207 of the Immigration and Nationality Act (8 U.S.C. 1157), the number of refugees who may be admitted during the remainder of fiscal year 2007 and during fiscal year 2008 under subsection (c) of such section shall be increased by not fewer than 20,000 for the purpose of admitting refugees from Iraq. (b) Prioritization.--The following groups shall me considered Priority 2 refugees of special humanitarian concern under the refugee resettlement priority system: (1) Female-headed households and unaccompanied children. (2) Religious communities of antiquity, including Chaldo- Assyrian Christians, Jews, Sabean Mandeans, Yazidis, Bahais, and others. (3) Other religious, ethnic, social, or minority groups, including gay and lesbian Iraqis, subject to violence, intimidation, or discrimination by state or non-state actors. (4) Iraqis with family members in the United States. SEC. 7. SECURITY AND RELATED GROUNDS FOR INADMISSIBILITY. (a) In General.--Section 212(d)(3)(B)(i) of the Immigration and Nationality Act (8 U.S.C. 1182(d)(3)(B)(i)) is amended to read as follows: ``(B)(i) The Secretary of State, after consultation with the Attorney General and the Secretary of Homeland Security, or the Secretary of Homeland Security, after consultation with the Secretary of State and the Attorney General, may determine in such Secretary's sole unreviewable discretion that subsection (a)(3)(B) shall not apply with respect to an alien within the scope of that subsection, or that subsection (a)(3)(B)(vi)(III) shall not apply to a group. Such a determination shall neither prejudice the ability of the United States Government to commence criminal or civil proceedings involving a beneficiary of such a determination or any other person, nor create any substantive or procedural right or benefit for a beneficiary of such a determination or any other person. Notwithstanding any other provision of law (statutory or non-statutory), including section 2241 of title 28, United States Code, or any other habeas corpus provision, and sections 1361 and 1651 of such title, no court shall have jurisdiction to review such a determination except in a proceeding for review of a final order of removal pursuant to section 242 and only to the extent provided in subsection (a)(2)(D) of such section. The Secretary of State may not exercise the discretion provided in this clause with respect to an alien at any time during which the alien is the subject of pending removal proceedings under section 240.''. (b) Duress Exception.--Section 212(a)(3)(B)(iv)(VI) of the Immigration and Nationality Act (8 U.S.C. 1182(a)(3)(B)(iv)(VI)) is amended, in the matter preceding item (aa), by striking ``to commit an act that the actor knows'' and inserting ``to commit an act, other than an act carried out under duress, that the actor knows''. (c) Technical Correction.--Section 212(a)(3)(B)(ii) of the Immigration and Nationality Act (8 U.S.C. 1182(a)(3)(B)(ii)) is amended, in the matter preceding subclause (I), by striking ``Subclause (VII)'' and inserting ``Subclause (IX)''. (d) Regulations.--Not later than 180 days after the date of the enactment of this section, the Secretary of Homeland Security and the Secretary of State shall each publish in the Federal Register regulations establishing the process by which the eligibility of a refugee, asylum seeker, or individual seeking to adjust the immigration status of such individual is considered eligible for any of the exceptions authorized by clause (i) of section 212(d)(3)(B) of the Immigration and Nationality Act (8 U.S.C. 1182(d)(3)(B)), including a timeline for issuing a determination relating thereto. (e) Effective Date.--The amendments made by this section shall take effect on the date of the enactment of this section. Such amendments and sections 212(a)(3)(B) and 212(d)(3)(B) of the Immigration and Nationality Act (8 U.S.C. 1182(a)(3)(B) and 1182(d)(3)(B)) shall apply to-- (1) removal proceedings instituted before, on, or after the date of the enactment of this section; and (2) acts and conditions constituting a ground for inadmissibility, excludability, deportation, or removal occurring or existing before, on, or after such date. (f) Waiver of Limitation on United States Emergency Refugee and Migration Assistance Fund.--Funds appropriated or otherwise made available for each of fiscal years 2008 and 2009 for the United States Emergency Refugee and Migration Assistance Fund established under section 2(c)(2) of the Migration and Refugee Assistance Act of 1962 (22 U.S.C. 2601(c)(2)) shall not be subject to the limitation contained in the second sentence of such section. SEC. 8. AUTHORIZATIONS OF APPROPRIATIONS. (a) United States Emergency Refugee and Migration Assistance Fund.--There is authorized to be appropriated such sums as may be necessary to carry out the provisions of section 2(c) of the Migration and Refugee Assistance Act of 1962 (22 U.S.C. 2601(c)) for assistance to Iraqi refugees. (b) Migration and Refugee Assistance.--There is authorized to be appropriated such sums as may be necessary to the Migration and Refugee Assistance account of the Department of State, of which-- (1) for assistance to Iraqi refugees in countries of first asylum through international nongovernmental organizations; (2) for a contribution to the United Nations High Commissioner for Refugees; (3) for a contribution to the International Committee of the Red Cross; and (4) for the resettlement in the United States of Iraqis admitted to the United States as special immigrants or refugees under this Act. (c) Office of Refugee Resettlement.--There is authorized to be appropriated such sums as may be necessary to the Office of Refugee Resettlement of the Department of Health and Human Services for the resettlement in the United States of Iraqi refugees. (d) Department of Homeland Security.--There is authorized to be appropriated such sums as may be necessary to the Secretary of Homeland Security for expedited refugee processing and the temporary expansion of the Refugee Corps of United States Citizenship and Immigration Services of the Department of Homeland Security. (e) International Disaster and Famine Assistance Account.--There is authorized to be appropriated such sums as may be necessary to the International Disaster and Famine Assistance account of the Department of State for assistance to internally displaced Iraqis. (f) FBI.--There is authorized to be appropriated such sums as may be necessary to the Federal Bureau of Investigation to expedite background checks and processing for Iraqis admitted to the United States as special immigrants or refugees under this Act. (g) Diplomatic and Consular Programs.--There is authorized to be appropriated to such sums as may be necessary to the Diplomatic and Consular Programs account of the Department of State to increase capacity to process special immigrant visas for Iraqis. (h) Amounts and Availability.--Amounts authorized to be appropriated under this section shall be in addition to amounts for such purposes that are otherwise authorized to be appropriated. Amounts appropriated under this section are authorized to remain available until expended.
Responsibility to Iraqi Refugees Act of 2007 - Authorizes the Secretary of Homeland Security to provide special immigrant status to an Iraqi national (and spouse or child of such alien) who: (1) worked directly with the U.S. government, the United Nations, certified government or U.N. contractor or subcontractor, or U.S.-based nongovernmental organization for at least one year; and (2) has a not manifestly unfounded fear of persecution, violence, or harm to the alien or the alien's family because of such work. Sets forth annual entry limits through FY2011 for such aliens. Directs the Secretary of State to: (1) provide such aliens who are in imminent danger with protection, including temporary housing on U.S. military bases or at provincial reconstruction team offices or immediate removal from Iraq; and (2) establish at least five alien processing facilities in Iraq. Establishes in the Department of State a Special Coordinator for Iraqi Refugees and Internally Displaced Persons, to be based at the U.S. embassy in Baghdad, Iraq. States that the Special Coordinator shall be responsible for the development and implementation of policies and programs for Iraqi refugees and internally displaced persons, and shall establish a related inter-agency task force. Directs the Secretary of State to seek to negotiate a bilateral refugee resettlement agreement with each country containing a significant population of displaced Iraqis, including Jordan, Syria, Turkey, and Lebanon. Increases FY2007-FY2008 refugee admissions for persons who are not not firmly settled in a foreign country and who are of humanitarian concern to the United States in order to admit Iraqi refugees. Sets forth priority groups. Revises the authority of the Secretary of State or the Secretary of Homeland Security to determine that security and related grounds for inadmissibility shall not apply to an individual or a group. Waives the FY2008-FY2009 funding cap for the United States Emergency Refugee and Migration Assistance Fund. Authorizes appropriations to specified entities and agencies for Iraqi refugee-related assistance.
since weinberg first proposed applying the ideas of effective field theory ( eft ) to nuclear forces @xcite , much effort has gone into this approach . ( for reviews , see refs . although there is still some debate about how best to implement it at energies where pion - exchange forces are resolved , the picture is clearer at lower energies . here few - nucleon systems can be described by a pionless " eft based on two- and three - body contact interactions @xcite . the resulting expansion of the two - body force is just that of the effective - range expansion @xcite , but the eft framework makes it possible to extend this consistently to other effective operators and three - body forces . this theory has been applied extensively to two - body systems , where it has been extended to include the effects of the coulomb interaction on proton - proton scattering @xcite . in that system , it corresponds to a distorted - wave or modified " version of the effective - range expansion @xcite . three - body systems have also been studied in the pionless eft @xcite . in these , exchange of one particle between an interacting pair and the third particle leads to a long - range force that can be either attractive or repulsive depending on the overall symmetry of the wave function . attractive channels , such as the triton , display the efimov effect @xcite in the limit of infinite two - body scattering length . this consists of an infinite tower of bound states with energies in a constant ratio . it results from a discrete scale invariance in these systems and corresponds to a limit cycle of the renormalisation group ( rg ) for the contact three - body force @xcite . the @xmath0he nucleus is of particular interest since it can potentially provide access to properties of the neutron that require a polarised target . it should be possible to describe its low - energy properties within the pionless eft , extended to include the coulomb interaction . however the only previous application of the theory to the @xmath4 system is in the work of rupak and kong , who treated coulomb effects perturbatively and only considered the spin-3/2 channel @xcite . a nonperturbative treatment may not be essential for the @xmath0he ground state , given the typical momenta in the wave function . however it will be necessary if the eft is to be extended to describe @xmath4 scattering near threshold . also , it is needed to answer the question of whether the efimov effect survives in the presence of the coulomb interaction . arguments based on the degrees of the singularities in the potentials suggest it should and this has been checked by hammer and higa for a simpler two - body model @xcite . however it has not previously been confirmed in a three - body system . like most other eft studies of the triton and other three - body systems @xcite , our treatment is formulated in terms of a set of integral equations . however a quite different approach , based on the resonating - group method , was recently applied to three- and four - nucleon systems by kirscher _ et al . _ while this also treats the coulomb interaction to all orders , limitations on the range of cutoffs mean that it is not able to test whether the efimov effect occurs . here we report the results of a study of @xmath0he in the pionless eft with the coulomb interaction treated nonperturbatively . our approach is based on that used by kok _ @xcite to study @xmath0he with separable potentials and the full off - shell coulomb @xmath1-matrix . the resulting set of integral equations is very similar to that developed by skornyakov and ter - martirosian@xcite which have more recently been used in eft studies of the triton and other three - body systems @xcite . our results show that the efimov effect does indeed occur in the presence of the coulomb interaction . we also determine the strength of the three - body force needed to reproduce observed @xmath0he binding energy . the difference between this and the corresponding force needed for the triton is of the expected size for an electromagnetic effect . in the pionless eft , the strong forces between nucleons are described by two- and three - body contact interactions . in the present context it is convenient to represent the two - body interactions in terms of dibaryon fields . the resulting effective lagrangian for the three - nucleon system can be written as @xcite & = & l_n + l_s + l_t + l_3 , where @xmath5 is the standard one - nucleon lagrangian in the heavy - baryon formalism , _ n & = & n^\ { ivd + } n. here @xmath6 is a velocity vector satisfying a condition @xmath7 , @xmath8 is the covariant derivative , and @xmath9 is the nucleon mass . the terms @xmath10 and @xmath11 are dibaryon effective lagrangian for spin singlet and triplet parts , respectively , and these read _ s & = & s_a^\ { ivd + _ s(a ) } s_a -y_s \ { s_a^+ h.c . } , + l_t & = & t_i^\ { ivd + _ t } t_i -y_t \ { t_i^+ h.c . } , where @xmath12 and @xmath13 are the corresponding dibaryon fields . the strengths of the corresponding two - body interactions depend on @xmath14 and @xmath15 , the mass differences between the dibaryons and two nucleons , and @xmath16 and @xmath17 , the coupling constants for the dibaryon - nucleon - nucleon vertices . the projection operators for the two - nucleon @xmath18 and @xmath19 states are p^(^1s_0)_a = _ 2_a _ 2 , p^(^3s_1)_i = _ 2_2_i , where @xmath20 and @xmath21 are pauli matrices for isospin and spin , respectively . the present work is based on the leading - order ( lo ) terms in the expansion of this eft of @xmath22 . here @xmath22 stands for any of the low - energy scales in the problem : the relative momenta , @xmath23 where @xmath24 is any of the nn scattering lengths , and the inverse of the bohr radius @xmath25 . more precisely , we keep all terms of order @xmath26 , noting that the strong attraction in the nn @xmath27 waves enhances the wave functions near the origin and hence promotes contact interactions proportional to @xmath23 or @xmath28 to this order @xcite . the coulomb interaction leads to a well - known logarithmic divergence in the nn loop integrals @xcite . this is renormalised by a lo counterterm that contributes to the @xmath29 scattering length . given that we need to include isospin breaking in this channel , we have also taken account of charge - independence breaking between the @xmath30 @xmath31 and @xmath32 scattering lengths , even though this is formally of higher order . this allows us to present the general structures of the three - body equations , which will be needed for extensions of this work to higher orders . we have not included the neutron - proton mass difference which is not only of higher order but is smaller than might be expected as a result of cancellations between electromagnetic and strong contributions @xcite . to the order we work , observables depend only on the combinations @xmath33 and so we have chosen to leave the couplings @xmath16 isospin - invariant . the three - body force is expressed as a dibaryon - nucleon contact interaction . it is given by the effective lagrangian , _ 3 & = & \ { y_t^2 n^ ( ) ^()n -y_sy_t + & & + y_s^2 n^()^ ( ) n } , [ eq;l3 ] where @xmath34 is the coupling constant , which runs with the scale @xmath3 of the cutoff we impose on the coupled integral equations . note that this interaction contributes only to three - body channels with total spin 1/2 and total isospin 1/2 . the building blocks needed to construct the three - body integral equations from the lagrangian are as follows . in the one - body sector , we have the non - relativistic nucleon propagator , is_n(p ) & = & . in the two - body sector , we need the dressed dibaryon propagators with and without the coulomb interaction . the propagators for the @xmath31 and @xmath32 channels , which have no coulomb interaction , are represented by the diagrams in fig . [ fig;dibaryonpropagator ] and are given by id_s , t(e- ) & = & . the two - nucleon loop diagrams here have been dimensionally regularised using the pds scheme with the subtraction scale @xmath35 . the dependence on this can be removed by renormalising the constants @xmath36 using + = , + = , + = , where @xmath37 and @xmath38 are the scattering lengths for the spin - singlet @xmath31 and @xmath32 channels , respectively , and @xmath39 is related to the deuteron binding energy @xmath40 through @xmath41 . working to leading order , we neglect corrections from the effective ranges . channel , denoted by the double line with shaded circle . the shaded ovals here represent the two - nucleon green s function dressed with the coulomb interaction.,width=566 ] in the @xmath29 channel , the coulomb interaction dresses the two - nucleon green s function in the bubble diagram for the dressed dibaryon propagator , as shown in fig . [ fig;dibaryonpropagator - with - coulomb ] . the resulting propagator is given by id_s(pp)(e- ) & = & , where h ( ) & = & ( i ) + -(i ) , @xmath42 is the logarithmic derivative of the @xmath43 function , and @xmath44 . the renormalised constant @xmath45 for the @xmath29 channel cancels both the linear and logarithmic divergences of the loop diagram . it is related to the coulomb scattering length @xmath46 by & = & = + -2 , where @xmath47 is euler s constant . note that the logarithmic divergence means that it is impossible to make a model - independent decomposition of @xmath48 into strong and electromagnetic contributions @xcite . this implies that within this eft there is no unambiguous way to separate coulomb from other isospin - breaking effects . the final building block for the integral equations is the off - shell coulomb t - matrix . a convenient form for it is the integral representation @xcite for negative energies , @xmath49 : |t_c(k^2/m_n)|*p*&= & , where @xmath50 and x^2 = 1 + . now we construct the integral equations for scattering of a third nucleon off a deuteron , concentrating on the channels where the third nucleon is in an @xmath27 wave , and the total spin and isospin of the three particles are both 1/2 . the negative - energy solutions of these describe the bound triton and @xmath0he states . we work the center of mass frame for the @xmath51 scattering and use the notation of bedaque _ et al . _ @xcite . in the isospin - symmetric case , this process can be described by an amplitude @xmath52 for scattering into states with a @xmath53 dibaryon , and @xmath54 for scattering into those with a @xmath30 dibaryon . here @xmath55 denotes the initial ( on - shell ) relative momentum of the deuteron and the third nucleon , and @xmath56 the final ( off - shell ) momentum . the amplitudes satisfy coupled integral equations which can be represented diagrammatically as in fig . [ fig;integral - equations ] . the kernels of these equations consist of two terms : one - nucleon - exchange , which provides a long - range force between the dibaryon and the third nucleon , and the three - body contact interaction . in the limit of infinite two - body scattering lengths ( and zero deuteron binding energy ) the long - range force is scale - independent . it is this feature that leads to the efimov effect in channels where the force is attractive . and @xmath30 dibaryons . those with filled circles are dressed dibaryon propagators , as in fig . [ fig;dibaryonpropagator ] . ovals with stripes denote the off - shell amplitude @xmath52 with initial and final spin - triplet dibaryons , and those with cross stripes the amplitude @xmath54 with initial spin - triplet and final spin - singlet dibaryon fields.,width=529 ] when we include the coulomb interaction , isospin symmetry is broken and we must introduce separate amplitudes @xmath57 and @xmath58 for @xmath4 scattering into states with @xmath30 @xmath29 and @xmath31 dibaryons , respectively . these and @xmath52 satisfy a set of three coupled integral equations . for completeness , we also present the corresponding set of three equations that arise when we allow for isospin - breaking effects in the @xmath59 case , involving the amplitude @xmath60 for states with @xmath32 dibaryons . as already mentioned , these are not essential for the present lo calculations but will be needed for extensions to higher orders . before presenting the equations for @xmath4 scattering , we first look at the simpler equations for @xmath59 scattering . allowing for isospin breaking in the scattering lengths , the three integral equations for the @xmath61 , @xmath62 channel are a(p , k ) & = & k^(a)(p , k;e ) + 2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 , [ eq;a - iso - b ] + b_0(p , k ) & = & 3 k^(a)(p , k;e ) + 2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 , [ eq;b0-iso - b ] + b_-(p , k ) & = & 3 k^(a)(p , k;e ) + 2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 , [ eq;bm - iso - b ] where k^(a)(p , q;e ) & = & ( ) . [ eq;one - kernel ] if we set @xmath63 and @xmath64 , these reduce to the isospin - symmetric forms of the equations in ref . @xcite . the integrals over the relative momentum @xmath65 are all cut off at @xmath66 . the resulting dependence on @xmath3 can be cancelled by the three - body force , whose strength is @xmath67 . we now turn to the corresponding equations for @xmath4 scattering . these differ from the ones in the previous subsection by having @xmath68 instead of @xmath69 and , more importantly , adding the coulomb interaction between the two protons . they can be obtained from the equations developed by the groningen group @xcite , by omitting the separable form factors and instead imposing a sharp cutoff on the relative momenta . the coulomb interaction leads to additional long - range terms in the kernels of these equations . the diagrams for the full long - range kernel are shown in fig . [ fig;fp ] . the one - nucleon exchange term of diagram ( a ) is supplemented by diagram ( b ) if a proton is exchanged , and by ( c ) for neutron exchange . finally , diagram ( d ) represents the coulomb interaction between an @xmath31 dibaryon and a proton . [ h ] scattering . here , the shaded oval denotes the off - shell coulomb @xmath1-matrix ( since contributions where the two protons do not interact are already contained in ( a ) ) . diagram ( b ) has been shown for the case of an initial @xmath31 dibaryon and a final @xmath29 one . the corresponding diagram for the inverse process is the mirror image of this.,title="fig:",width=453 ] the coupled integral equations can be written a(p , k ) & = & k^(a)(p , k;e ) + k^(c)(p , k;e ) + 2 k^(d)(p , k;e ) + 2 + & & + ^_0 dqq^2 + & & + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 , + & & + b_0(p , k ) & = & 3 k^(a)(p , k;e ) + 3 k^(c)(p , k;e ) + 2 + & & + ^_0 dqq^2 + & & - ^_0 dqq^2 + & & + & & + ^_0 dqq^2 , + & & + b_+(p , k ) & = & 3 k^(a)(p , k;e ) + 3 k^(b)_31(p , k;e ) + 2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 + & & + ^_0 dqq^2 , where @xmath70 is the one - nucleon exchange kernel defined in eq . ( [ eq;one - kernel ] ) above , and @xmath71 , @xmath72 , @xmath73 , and @xmath74 are the pieces corresponding to the coulomb diagrams ( b ) , ( c ) , ( d ) in fig . [ fig;fp ] . ( in @xmath75 and @xmath76 , the subscripts 1 and 3 refer to initial and final dibaryons , 1 denoting @xmath31 and 3 @xmath29 . ) in diagram ( b ) , the dibaryon - nucleon - nucleon vertex projects out only the @xmath27-wave part of the coulomb t - matrix . this considerably simplifies the corresponding terms in the equations by reducing the number variables that need to be integrated from six to two . the corresponding terms in the kernels are k_13^(b)(p , q;e ) & = & 12 ^ 1_-1dy , + k_31^(b)(p , q;e ) & = & 12 ^ 1_-1dy , where @xmath77 and _ 13^(b)(p , q , y;e ) & = & - ^1_0 dtt^/ , + _ 31^(b)(p , q , y;e ) & = & - ^1_0 dtt^/ . here we have defined the momentum variables p = |*p*+12*q*| , p = |*q*+12*p*| , = , = . the kernels for diagrams ( c ) and ( d ) involve six dimensional integrals but we can analytically evaluate two of these ( over the azimuthal angles ) . in the case of @xmath73 , it is convenient to introduce the vectors , = * p*+*q * , = * p*-*q * , choosing axes where @xmath78 lies along the @xmath79-direction , these can be written = a(0,0,1 ) , = b(,0 , ) , = l(,, ) , in terms of their magnitudes a = , b = , and the angles defined by = , the kernel then becomes k^(c)(p , q;e ) & = & -^_0 dl ^1_-1d ( ) ^1_-1d( ) ^1_0 dt + & & ( . - ) , [ eq;kc ] where y_1,2 & = & , + d&= & l^2+p^2+q^2+pq-32al-m_ne , + ^2 & = & 34(l^2+a^2 + 2al)-m_ne . the last term in the kernel , arising from diagram ( d ) , requires the most care in its numerical evaluation . this is because the long - range photon exchange gives rise to a logarithmic ir singularity . in the present work , where we are interested only in bound states , the finite extent of the wave functions helps to regulate this singularity . calculations of @xmath4 scattering amplitudes will , however , require different numerical methods . following ref . @xcite , we split @xmath74 up into three pieces , k^(d)(p , q;e ) & = & k^(d , v)(p , q;e ) + k^(d , v)(p , q;e ) + k^(d , t - v)(p , q;e ) , [ eq;kd ] where @xmath80 and @xmath81 denote the contributions the from singular and nonsingular parts of one - photon exchange , and @xmath82 the remaining ( also nonsingular ) terms from iterating the coulomb potential . these have pieces have the forms k^(d , v)(p , q;e ) & = & - ( ) , [ eq;kdvp ] + k^(d , v)(p , q;e ) & = & -^1_-1d()\ { . + & & - } , + k^(d , t - v)(p , q;e ) & = & -^1_-1d ( ) + & & \ { ^_0dll^2 ^ 1_-1d()^1_0dt + & & - } , where & = & , = , _ l = , + d & = & ( l^2+q^2+ql - m_ne)(l^2+p^2+pl - m_ne ) + & & + 4t(1-t)^-2_l^2 ( p^2+q^2 - 2pq ) , + c & = & ( l^2+q^2+ql - m_ne)pl/d . we solve for the three - body bound states by taking the homogeneous parts of the coupled integral equations and treating them as nonlinear eigenvalue problems , k(e)u= u , [ eq;xx ] where @xmath83 and the @xmath84 matrices of integral operators @xmath85 can be extracted from the expressions in the previous section . to convert @xmath85 into a matrix we use gauss - legendre quadrature to replace the momenta @xmath56 and @xmath65 by discrete variables . we have examined three versions of this discretisation , in terms of variables @xmath86 defined by : ( 1 ) @xmath87 where @xmath88 mev , ( 2 ) @xmath89 ( no change of variable ) , and ( 3 ) @xmath90 where @xmath91 mev . the variables @xmath56 and @xmath65 run from zero to the cutoff @xmath3 , except in the third of these where we also need to impose a cutoff at the very small momentum @xmath92 . we the construct the determinant of the matrix @xmath93 and search on @xmath94 to find the energy eigenvalues at which @xmath95=0 $ ] . for one of these values of @xmath94 , we then solve the eigenvalue problem eq . ( [ eq;xx ] ) and determine the eigenvector corresponding to the unit eigenvalue of the matrix @xmath85 . for given values of the two - body input parameters we first set the three - body force @xmath34 to zero and adjust the value of the cutoff until the shallowest bound - state eigenvalue reproduces the observed three - body binding energy . starting from this cutoff , @xmath96 , we then determine the values of @xmath34 needed to reproduce this binding energy for other cutoffs . in this case , we work with the determinant constructed from the homogeneous part of the coupled integral equations in eqs . ( [ eq;a - iso - b ] ) , ( [ eq;b0-iso - b ] ) , and ( [ eq;bm - iso - b ] ) . the two - body input is provided by = 45.703 , a_np = -23.749 0.008 , a_nn = -18.50.4 . we adjust the three - body force to fit the triton binding energy , b_3(^3 ) = 8.48182 , which corresponds to a momentum scale @xmath97 mev . for 16 gaussian integration points ( corresponding to a 48@xmath9848 matrix ) we find that our results have converged and , for the three choices of variable discussed above , they agree to 6 significant figures . as a function of the cutoff @xmath3 in mev . for comparison , the dashed curve shows the asymptotic , scale - free form of @xmath34 . , width=529 ] for @xmath99 , we reproduce the experimental binding energy with the cutoff @xmath100 mev . the values of the three - body force needed for other cutoffs are shown in fig . [ fig;h - triton - isb ] . as we take @xmath101 , the cutoff becomes much larger than the physical scales in the system ( @xmath23 ) and @xmath34 displays the limit - cycle behaviour found in ref . this reflects the presence of the efimov effect in this three - body system , a tower of deeply bound states with energies in a constant ratio @xcite . in three - nucleon systems only the shallowest of these states lies within the domain of the eft and so corresponds to a physical state . the asymptotic form of @xmath34 in this limit is @xcite h ( ) = - . [ eq;h ] where @xmath102 and the scale parameter @xmath103 is defined by _ 0 = _ * . this form is shown by the dashed line in fig . [ fig;h - triton - isb ] . the numerical results deviate from it only for small values of @xmath3 where the finite scattering lengths can influence the renormalisation of the three - body force . for the @xmath104he channel , we need to the @xmath29 coulomb scattering length as a two - body input parameter , a_c=-7.80630.0026 . the experimental binding energy of @xmath104he is b_3(^3 ) = 7.71804 , corresponding to a scale @xmath105 mev as already noted , the @xmath80 term contains a logarithmic singularity that needs to be dealt with carefully . we handle it with the method outlined in appendix b in ref . @xcite . in the case of a bound state , the other factors in the integral are regular and so the logarithmic singularity has a finite integral . we can take the interval around the singular point and , treating the other factors as constant , explicitly integrate the logarithm over it . the result can be expressed in a similar form to a gaussian quadrature , ^b_a dq ( p_j - q)^2 y(q ) = _ ij^n w_i ( p_j - q_i)^2 y(q_i)+w_j^ y(p_j ) , where @xmath106 is a smooth function and the @xmath107 are the usual weights . the modified weight for the singular point is given by w_j^&= & ^q_j>_q_j < dq ( p_j - q)^2 + & = & -2w_j+2(q_j>-p_j)(q_j>-p_j ) + 2(p_j - q_j<)(p_j - q_j < ) , where @xmath108 and @xmath109 . to examine the size of coulomb effects in the three - nucleon system , we first consider an isospin - symmetric three - body force and take @xmath110 for the same value @xmath100 mev as in the triton . we use @xmath111 gaussian points for the four integrals needed to evaluate the kernels @xmath73 and @xmath74 . the integral equations are discretised using up to @xmath112 points ( leading to @xmath113 matrices ) . we fit the results for @xmath114 and 32 to the form @xmath115 in order to extrapolate to @xmath116 . using the first choice for the discretisation variable ( @xmath87 ) , we get @xmath117 mev , or a binding energy of @xmath118 mev . this differs from the triton energy for the same three - body force by 0.82 mev . it is within 1% of the observed @xmath0he energy , indicating that the isospin - violating three - body force is indeed a higher - order contribution . this is as expected , given the absence of any modification of the renormalisation , since the isospin - violating term is suppressed by one power of the inverse bohr radius @xmath28 relative to the lo force . of the three - body forces @xmath34 for @xmath0he ( solid line ) and the triton ( dashed).,width=529 ] our difference between the triton and @xmath0he binding energies is significantly larger than the @xmath119 mev found by kirscher _ et al . _ however , although working to nlo , those authors took a charge - independent value for the @xmath30 scattering length . their results are consistent with other estimates of the pure coulomb contribution @xcite . because we take different values for the @xmath32 and @xmath31 @xmath30 scattering lengths , our calculations do include some higher - order isospin - breaking effects . given that we have not done a consistent calculation to n@xmath120lo ( or even nlo ) , the best we can say is that the @xmath121160 kev difference between our result and that of ref . @xcite is comparable in size to the contributions of 70110 kev that have been estimated using other approaches @xcite . one caveat that should be made about these comparisons is that , as noted above , there is no model - independent way to separate coulomb and other isospin - breaking effects in this eft . by adjusting the strength of the three - body force , we can fit the experimental binding energy . as in the triton case , we have done this for a range of cutoffs . the results are plotted in fig . [ fig;h-3he ] . they display the same limit - cycle behaviour as in the triton channel . moreover the differences between the forces needed in the two channels are very small , reflecting the fact that a symmetric force can give a very good account of @xmath0he . to quantify the size of the isospin breaking in the three - body forces , it is better not to consider the values of @xmath34 , since these cycle between @xmath122 . the scale @xmath96 or , equivalently @xmath103 , is a more appropriate measure . its value of @xmath123 mev differs from that for the triton by 0.46% . the contribution of this force to the triton-@xmath0he splitting is about 50 kev . this is much larger than the 5 kev estimate of the three - body contribution in ref . @xcite , which may reflect the fact that other isospin - breaking effects are missing from our calculatation . also , the results of ref . @xcite were obtained using an eft that includes pion fields . we have studied @xmath0he within the framework of the pionless eft , treating the coulomb interaction nonperturbatively . we solve the set of integral equations developed by kok _ et al . _ @xcite , which can be thought of as extending the equation of skornyakov and ter - martirosian @xcite to include the full off - shell coulomb @xmath1-matrix . we find that a three - body interaction is required at leading order in @xmath0he , as in the triton . this force also exhibits the same limit - cycle behavior as a function of the cutoff @xmath3 as found by bedaque _ et al . _ @xcite for systems with purely short - range interactions . these results show that the coulomb interaction is not singular enough to alter the deeply bound efimov " states in the three - nucleon system . we find that an isospin symmetric three - body force , fit to the triton binding energy , can give the @xmath0he binding to better than 1% . the scale parameter of the force that fits @xmath0he differs from the corresponding value for the triton by about 0.5% . this is of the expected size for an order-@xmath124 electromagnetic effect . our results demonstrate that the coulomb interaction has no nonperturbative effect on the renormalisation of the three - body force in @xmath0he . moreover the overall contributions of the coulomb interaction to the binding energy of @xmath0he are small , perhaps unsurprisingly given the typical momenta involved , and so could have been calculated perturbatively . this will not be the case if our approach is extended to describe low - energy @xmath4 scattering . however , as noted above , such an extension will require improved numerical techniques to handle the singularity of the coulomb interaction . our approach could also be used to determine the @xmath0he wave function from the corresponding eigenvector of the set of integral equations . this could then be used in calculations of electromagnetic properties of @xmath0he , based on the methods in ref . . our present results do include certain other isospin - breaking effects beyond lo in this eft , through the @xmath32 and @xmath31 @xmath30 scattering lengths . a proper treatment of these in the three - nucleon system will require a consistent higher - order calculation . we have provided here the basic forms of the integral equations allowing for isospin - breaking in the nn scattering lengths . the relevant power counting for the terms needed in a full calculation can be determined using the techniques in refs . this work was supported by stfc grants pp / f000448/1 and st / f012047/1 . we are grateful to l. kok and his colleagues in groningen for providing copies of the reports @xcite . s. weinberg , phys . b251 * , 288 ( 1990 ) ; nucl . phys . * b363 * , 3 ( 1991 ) . s. r. beane , p. f. bedaque , w. c. haxton , d. r. phillips and m. j. savage , _ at the frontier of particle physics : handbook of qcd _ , ed . m. shifman , vol . 1 , p. 133 ( world scientific , singapore , 2001 ) . p. f. bedaque and u. van kolck , ann . nucl . part . sci . * 52 * , 339 ( 2002 ) . e. epelbaum , prog . . phys . * 57 * , 654 ( 2006 ) . p. f. bedaque and u. van kolck , phys . * b428 * , 221 ( 1998 ) . u. van kolck , nucl . phys . * a645 * , 273 ( 1999 ) . d. b. kaplan , m. j. savage , and m. b. wise , phys . b424 * , 390 ( 1998 ) ; nucl . phys . * b534 * , 329 ( 1998 ) . f. bedaque , h .- w . hammer and u. van kolck , nucl . phys . a 676 , 357 ( 2000 ) . h. a. bethe , phys . rev . * 76 * , 38 ( 1949 ) . x. kong and f. ravndal , phys . lett . * b450 * , 320 ( 1999 ) . x. kong and f. ravndal , phys . c * 64 * , 044002 ( 2001 ) . t. barford and m. c. birse , phys . c * 67 * , 064006 ( 2003 ) . s. ando , j. w. shin , c. h. hyun and s .- w . hong , phys . c * 76 * , 064001 ( 2007 ) . s. ando and m. c. birse , phys . c * 78 * , 024004 ( 2008 ) . v. n. efimov , sov . * 12 * , 589 ( 1971 ) ; * 29 * , 546 ( 1979 ) . e. braaten and h .- w . hammer , phys . lett . * 91 * , 102002 ( 2003 ) . g. rupak and x. kong , nucl . phys . * a717 * , 73 ( 2003 ) . hammer and r. higa , eur . j. * a37 * , 193 ( 2008 ) . j. kirscher , h. w. griesshammer , d. shukla and h. m. hofmann , eur . j. a * 44 * , 239 ( 2010 ) . l. p. kok , d. j. struik , and h. van haeringen , university of groningen internal report 151 ( 1975 ) ; l. p. kok , d. j. struik , j. e. holwerda and h. van haeringen , university of groningen internal report 170 ( 1975 ) . g. v. skorniakov and k. a. ter - martirosian , sov . jetp , 648 ( 1957 ) . s. ando and c. h. hyun , phys . c * 72 * , 014008 ( 2005 ) . m. c. birse , j. a. mcgovern and k. g. richardson , phys . b464 * , 169 ( 1999 ) . m. c. birse , in _ proc . of the 6th international workshop on chiral dynamics _ , pos(cd09)078 ( 2009 ) . j. gasser and h. leutwyler , phys . * 87 * , 77 ( 1982 ) . j. c. y. chen and a. c. chen , adv . * 8 * , 71 ( 1972 ) . l. koester and w. nistler , z. phys . a * 272 * , 189 ( 1975 ) . g. f. de tramond and b. gabioud , phys . c * 36 * , 691 ( 1987 ) . j. r. bergervoet , p. c. van campen , t. a. rijken and j. j. de swart , phys . c * 38 * , 770 ( 1988 ) . s. a. coon and r. c. barrett , phys . c * 36 * , 2189 ( 1987 ) . y. wu , s. ishikawa and t. sasakawa , phys . lett . * 65 * , 3160 ( 1990 ) ; * 66 * , 242 ( 1991 ) . r. machleidt and h. mther , phys . c * 63 * , 034005 ( 2001 ) . j. l. friar , g. l. payne and u. van kolck phys . rev . c * 71 * , 024003 ( 2005 ) . h. sadeghi and s. bayegan , nucl . a753 * , 291 ( 2005 ) ; h. sadeghi , s. bayegan and h. w. griesshammer , phys . lett . * b643 * , 263 ( 2006 ) . p. f. bedaque , h. w. griesshammer , h .- w . hammer and g. rupak , nucl . a714 * , 589 ( 2003 ) . t. barford and m. c. birse , j. phys . a : math . gen . * 38 * , 697 ( 2005 ) .
@xmath0he and the triton are studied as three - body bound states in the effective field theory without pions . we study @xmath0he using the set of integral equations developed by kok _ et al . _ which includes the full off - shell @xmath1-matrix for the coulomb interaction between the protons . to leading order , the theory contains : two - body contact interactions whose renormalized strengths are set by the @xmath2 scattering lengths , the coulomb potential , and a three - body contact interaction . we solve the three coupled integral equations with a sharp momentum cutoff , @xmath3 , and find that a three - body interaction is required in @xmath0he at leading order , as in the triton . it also exhibits the same limit - cycle behavior as a function of @xmath3 , showing that the efimov effect remains in the presence of the coulomb interaction . we also obtain the difference between the strengths of the three - body forces in @xmath0he and the triton .
A US college student got very drunk and designed an entire plane. His friend’s tweet about it has gone viral and been retweeted more than 30,000 times. We talk to the guys … The news is, to put it mildly, pretty depressing recently – social media equally so. Twitter timelines are filled with the horrors of war and unspeakable tragedy, so it was a blessed relief that late on Sunday night a tweet which was a source of unadulterated joy started to go viral. Enter Keith Fraley, a 19-year-old second year student of software engineering at Michigan Tech college, and his tweet about his roommate, Mark, a mechanical engineering student, who arrived home wasted and managed to design an entire plane – and woke up with no memory the next day. Keith’s tweet has since been retweeted more than 30,000 times and been favourited almost 60,000 times. keith (@spasepeople) so my roommate came back drunk last night and doesnt remember designing an entire fucking airplane pic.twitter.com/A8El9Jyrn6 Keith and Mark – that’s not his real name, as he’s somewhat worried about his drinking exploits in the context of future employment – agreed to answer some questions about the fact that Michigan Tech students seem to have much more productive periods of being absolutely trashed than the rest of us, who are more usually found racing each other in shopping trolleys and hitting on our colleagues. We spoke to Keith, with input from Mark. What time did Mark come home, and what had he been drinking? Did he just bowl straight into the aircraft designing, or was there some lead up to this? It all started around 11.30pm. Mark burst into the room in a drunken sway, asking where his textbooks were and after greeting me he rushed back out of the room. From what the person who brought him up [to the shared accommodation] was saying, Mark had a ton of rum and vodka-mixed drinks. He then came stumbling back two minutes later to grab his giant whiteboard. I just laughed as I sat on the computer listening to his murmurs. Around 1.30am, he came back and he sat on the couch with a worn look on his face. He came stumbling back two minutes later to grab his giant whiteboard My friend Cody and I both looked at Mark as he then began to spew information about his whiteboard designed craft and the calculations behind it. Cody and I were in tears from laughter because the aerospace mathematics he tried telling us about sounded like a slurred robot. I did no encouraging towards the creation of this, but I did encourage him to continue talking because it was hilarious. Facebook Twitter Pinterest Keith Flaney and Mark, the designer of the plane. Photograph: Keith Flaney Was anyone else lucky enough to witness this? The guys that Mark shared drinks with were with him for more of the night than I was. They explained to me that Mark began a tantrum and began creating his design. Alex, a friend of Mark’s, said that he began staring at the ground and said that he asked for pen and paper immediately. After he sketched some designs, he said that he needed to leave and grab his aerospace mathematics textbook and whiteboard. According to his drinking buddies, he was drawing frantically explaining his thoughts out loud and at the time he was very intoxicated. He was passing out on his whiteboard from time to time as well. Mark’s designs are spread across graph paper, a whiteboard, and a notepad – that’s some real attention to detail and dedication … Mark, although very intelligent towards math, also works towards industrial design and some minor graphic designing. It is no surprise to me that his work while intoxicated was still very visually appealing. So, would the aircraft fly? Does the design hold up in a sober setting? Well technically, it’s not an airplane like I claimed. It’s actually called an ekranoplan, which is more like a very high speed aircraft that floats above the water (Mark is trying to dumb this down for me). Mark says that he imagines his design may work, and he looks forward to trying to recreate his work into a remote-control model with his colleagues … spookie jebbie⚛ (@debbiedontcare) @spasepeople this is the greatest thing I've seen on twitter all year Has there ever been any kind of inebriated ekranoplan designing before? Or is it normally the more usual fare of traffic cones on heads and falling over garbage cans? Well normally, we might slap “DRUNK” stickers on our foreheads, but Mark has brought new light to those of us who are unproductive drinkers. Most would think his actions were a result of Adderall or some crazy LSD but his actions were just down to being blackout drunk. How does it feel for your tweet to have gone viral? It has now been retweeted almost 30,000 times and faved almost 50,000 times. Have your mentions been going crazy? It was funny to think the tweet up, I could see one of my tweets finally getting some spotlight from my friends , but I couldn’t have imagined it getting as much attention as it did. We were counting the notifications as it went from zero activity to 27,000 retweets and 50,000 favourites in around 12 hours. One person on Twitter said the tail prop would fail during steep climbs, due to low pressure behind the wing What kind of feedback have you had for the tweet? Are people just in hysterics, or have there been engineers out there actually commenting on the design? Almost all of the feedback we received was surprisingly positive, and many people joked saying that they wanted whatever Mark was having that night. A lot of people also commented saying “drunk goals”. One person did call Mark out on his design, saying that the tail prop would fail during steep climbs due to low pressure behind the wing, and Mark replied saying that his design was actually an ekranoplan and not an airplane – so it lead to humorous and constructive responses. ra6bit (@ra6bit) @spasepeople @hacks4pancakes That's both acceptable and makes the fact that he designed it while drunk funnier. Heh Does he genuinely not remember designing the ekranoplan? It’s actually really funny because he didn’t draw the design on the actual graph paper [in addition to the whiteboard] until he woke up the next morning. He woke me up and he must have been intoxicated still because as I watched him, he realised what he was doing and was struck with confusion and anger. Next time, he plans on curing cancer He doesn’t remember a thing – even the next morning at 9am. He then fell asleep in his chair and woke up about an hour later basically questioning his sanity because of the immense amount of work that was in front of him, with no memory of his motivation to do it. What does Mark plan on designing next time he is drunk? He plans on trying to cure cancer or to finalise his design plans for the craft in Siemens NX to be 3D printed later for prototyping. Finally, if you could both get drunk and design an aircraft with anyone in the world (dead or alive), who would it be? If we could both get drunk and design an aircraft, Mark explained that he would want it to be with the man who invented and designed the world’s first ekranoplan, Rostislav Alexeyev. I would probably just sit back and document the entire thing on Twitter. • You can follow Keith on Twitter: @spasepeople ||||| "Ekranoplan" redirects here. For the album by Assemble Head in Sunburst Sound, see Ekranoplan (album) A ground-effect vehicle (GEV) is a vehicle that is designed to attain sustained flight over a level surface (usually over the sea) by making use of ground effect, the aerodynamic interaction between the wings and the surface. Among the best known are the Soviet ekranoplans, but names like wing-in-ground-effect (WIG), flarecraft, sea skimmer, or wing-in-surface-effect ship (WISE) are also used. In recent years a large number of different GEV types have been developed for both civilian and military use. However, these craft have yet to enter widespread use. Although they may look and have related technical characteristics similar to seaplanes, ground-effect vehicles are generally not designed to fly out of ground effect. They are also dissimilar from hovercraft or hydrofoils, as they do not have any contact with the surface of the water when in "flight". Ground-effect vehicles constitute a completely unique class of transportation. Design [ edit ] A ground-effect vehicle needs some forward velocity to produce lift dynamically and the principal benefit of operating a wing in ground effect is to reduce its lift-dependent drag. The basic design principle is that the closer the wing operates to an external surface such as the ground, said to be in ground effect, the more efficient it becomes. An airfoil passing through air increases air pressure on the underside, while decreasing pressure across the top. The high and low pressures are maintained until they flow off the ends of the wings, where they form vortices which in turn are the major cause of lift-induced drag—normally a large portion of the drag affecting an aircraft. The higher the aspect ratio of the wing (that is, the longer and skinnier it is), the less induced drag created for each unit of lift and the greater the efficiency of the particular wing. This is the primary reason gliders have long and skinny wings. Placing the same wing near a surface such as the water or the ground has the effect of greatly increasing the aspect ratio, but without having the complications associated with a long and slender wing, so that the short stubs on an Ekranoplan can produce just as much lift as the much larger wing on a transport aircraft, though it can only do this when close to the earth's surface. Once sufficient speed has built up, some GEVs may be capable of leaving ground effect and functioning as normal aircraft until they approach their destination. The distinguishing characteristic is that they are unable to land or take off without a significant amount of help from the ground effect cushion, and cannot climb until they have reached a much higher speed. A GEV is sometimes characterized as a transition between a hovercraft and an aircraft, although this is not correct as a hovercraft is statically supported upon a cushion of pressurised air from an onboard downward-directed fan. Some GEV designs, such as the Russian Lun and Dingo, have used forced blowing under the wing by auxiliary engines to increase the high pressure area under the wing to assist the takeoff; however they differ from hovercraft in still requiring forward motion to generate sufficient lift to fly. Wing configurations [ edit ] Ekranoplan; (B) Reverse-delta wing; (C) Tandem wing. WIG-wings configurations: (A)Ekranoplan; (B)Reverse-delta wing; (C)Tandem wing. A Russian light ekranoplan Aquaglide-2 Ekranoplan wing [ edit ] This was the profile designed by Rostislav Alexeyev. The wings are significantly shorter than those of comparable aircraft, and this configuration requires a high aft-placed horizontal tail to maintain stability. The pitch and altitude stability comes from the lift slope[note 1] difference between a front low wing in ground effect (commonly the main wing) and an aft, higher-located second wing nearly out of ground effect (generally named a stabilizer). Reverse delta wing [ edit ] Developed by Alexander Lippisch, this wing allows stable flight in ground effect through self stabilization. This is the main Class B form of ground effect craft. Tandem wings [ edit ] Tandem wing can have two configurations: A biplane-style type-1 utilising a shoulder-mounted main lift wing and belly-mounted sponsons similar to those on combat and transport helicopters. A canard-style type-2 with a mid-size horizontal wing [note 2] near the nose of the craft directing airflow under the main lift airfoil. This type-2 tandem design is a major improvement during takeoff, as it creates an air cushion to lift the craft above the water at a lower speed, thereby reducing water drag, which is the biggest obstacle to successful seaplane launches. near the nose of the craft directing airflow under the main lift airfoil. This type-2 tandem design is a major improvement during takeoff, as it creates an air cushion to lift the craft above the water at a lower speed, thereby reducing water drag, which is the biggest obstacle to successful seaplane launches. A tandem wing style with double-wing system as tandem-airfoil flairboat constructions by the aerodynamic specialist Dipl. Ing. Günther W. Jörg. This system is self-stabilizing and provides secure, comfortable and high-efficiency operation. Classification [ edit ] One difficulty which has delayed GEV development is the classification and legislation to be applied. The International Maritime Organisation has studied the application of rules based on the International Code of Safety for High-Speed Craft (HSC code) which was developed for fast ships such as hydrofoils, hovercraft, catamarans and the like. The Russian Rules for classification and construction of small type A ekranoplans is a document upon which most GEV design is based. However, in 2005, the IMO classified the WISE or GEV craft under the category of ships.[1] The International Maritime Organisation recognizes three types of ground effect craft:[2] A craft which is certified for operation only in ground effect; A craft which is certified to temporarily increase its altitude to a limited height outside the influence of ground effect but not exceeding 150 m above the surface; and A craft which is certified for operation outside ground effect and exceeding 150 m above the surface. These classes currently only apply to craft carrying 12 passengers or more. Advantages and disadvantages [ edit ] Given similar hull size and power, and depending on its specific design, the lower lift-induced drag of a ground-effect craft, as compared to an aircraft of similar capacity, will improve its fuel efficiency and, up to a point, its speed. Ground-effect craft also are much faster than surface vessels of similar power, because they avoid drag from the water. On the water the aircraft-like construction of ground-effect craft increases the risk of damage, should they fail to avoid other vessels. Furthermore, the limited number of egress points make it more difficult to evacuate the vehicle in an emergency. Since most ground-effect craft are designed to operate from water, accidents and engine failure typically are less hazardous than in a land-based aircraft, but the lack of altitude control leaves the pilot with fewer options for avoiding collision, and to some extent that discounts such benefits. Low altitude brings high speed craft into conflict with ships, buildings and rising land, which may not be sufficiently visible in poor conditions to avoid, and the ground-effect vehicle may be unable to climb over or turn sharply enough to avoid collisions while drastic, low level maneuvers risk contact with solid or water hazards beneath. Aircraft can climb over most obstacles, but ground-effect vehicles are more limited. In high winds, take-off must be into the wind, which takes the craft across successive lines of waves, causing heavy pounding, which both stresses the craft and makes passengers uncomfortable. In light winds, waves may be in any direction, which can make control difficult as each wave causes the vehicle to both pitch and roll. Their light construction makes their ability to operate in higher sea states less than that of conventional ships, but greater than the ability of hovercraft or hydrofoils, which are closer to the surface of the water. The demise of the seaplane was a result of its inability to take off or land in rough sea conditions even while flying conditions were good, and its use only lasted until runways were more commonly available. Ground-effect vehicles are similarly limited. Like conventional aircraft, greater power is needed for takeoff, and, like seaplanes, ground-effect vehicles must get on the step before they can accelerate to flight speed. Careful design, usually with multiple redesigns of hullforms, is required to get this right, which increases engineering costs. This obstacle is more difficult for ground-effect vehicles with short production runs to overcome. For the vehicle to work, its hull needs to be stable enough longitudinally to be controllable yet not so stable that it cannot lift off the water. The bottom of the vehicle must be formed to avoid excessive pressures on landing and taking off without sacrificing too much lateral stability, and it must not create too much spray, which damages the airframe and the engines. The Russian Ekranoplans show evidence of fixes for these exact problems in the form of multiple chines on the forward part of the hull undersides and in the forward location of the jet engines. Finally, limited utility has kept production levels low enough that it has been impossible to amortize development costs sufficiently to make ground-effect vehicles competitive with conventional aircraft. History [ edit ] By the 1920s, the ground effect phenomenon was well-known, as pilots found that their airplanes appeared to become more efficient as they neared the runway surface during landing. In 1934 the US National Advisory Committee for Aeronautics issued Technical Memorandum 771, Ground Effect on the Takeoff and Landing of Airplanes, which was a translation into English of a summary of research up to that point on the subject. The French author Maurice Le Sueur had added a suggestion based on this phenomenon: "Here the imagination of inventors is offered a vast field. The ground interference reduces the power required for level flight in large proportions, so here is a means of rapid and at the same time economic locomotion: Design an airplane which is always within the ground-interference zone. At first glance this apparatus is dangerous because the ground is uneven and the altitude called skimming permits no freedom of maneuver. But on large-sized aircraft, over water, the question may be attempted ..."[3] By the 1960s, the technology started maturing, in large part due to the independent contributions of Rostislav Alexeyev in the Soviet Union[4] and German Alexander Lippisch, working in the United States. Alexeyev worked from his background as a ship designer whereas Lippisch worked as an aeronautical engineer. The influence of Alexeyev and Lippisch remains noticeable in most GEV vehicles seen today. Soviet Union [ edit ] Led by Alexeyev, the Soviet Central Hydrofoil Design Bureau (Russian: ЦКБ СПК) was the center of ground-effect craft development in the USSR. The vehicle came to be known as an ekranoplan (Russian: экранопла́н, экран screen + план plan, from Russian: эффект экрана, literally screen effect, or ground effect in English). The military potential for such a craft was soon recognized and Alexeyev received support and financial resources from Soviet leader Nikita Khrushchev. Some manned and unmanned prototypes were built, ranging up to eight tons in displacement. This led to the development of a 550-ton military ekranoplan of 92 m (302 ft) length. The craft was dubbed the Caspian Sea Monster by U.S. intelligence experts, after a huge, unknown craft was spotted on satellite reconnaissance photos of the Caspian Sea area in the 1960s. With its short wings, it looked airplane-like in planform, but would obviously be incapable of flight.[5] Although it was designed to travel a maximum of 3 m (9.8 ft) above the sea, it was found to be most efficient at 20 m (66 ft), reaching a top speed of 300–400 kn (560–740 km/h; 350–460 mph) in research flights. The Soviet ekranoplan program continued with the support of Minister of Defence Dmitriy Ustinov. It produced the most successful ekranoplan so far, the 125-ton A-90 Orlyonok. These craft were originally developed as high-speed military transports and were usually based on the shores of the Caspian Sea and Black Sea. The Soviet Navy ordered 120 Orlyonok-class ekranoplans, but this figure was later reduced to fewer than 30 vessels, with planned deployment mainly in the Black Sea and Baltic Sea fleets. A few Orlyonoks served with the Soviet Navy from 1979 to 1992. In 1987, the 400-ton Lun-class ekranoplan was built as a missile launcher. A second Lun, renamed Spasatel, was laid down as a rescue vessel, but was never finished. The two major problems that the Soviet ekranoplans faced were poor longitudinal stability and a need for reliable navigation. Minister Ustinov died in 1985, and the new Minister of Defence, Marshal Sokolov, cancelled funding for the program. Only three operational Orlyonok-class ekranoplans (with revised hull design) and one Lun-class ekranoplan remained at a naval base near Kaspiysk. Since the dissolution of the Soviet Union, ekranoplans have been produced by the Volga Shipyard[6] in Nizhniy Novgorod. Smaller ekranoplans for non-military use have been under development. The CHDB had already developed the eight-seat Volga-2 in 1985, and Technologies and Transport is developing a smaller version called the Amphistar. Beriev proposed a large craft of the type, the Be-2500, as a "flying ship" cargo carrier,[7] but nothing came of the project. Germany [ edit ] Lippisch Type and Hanno Fischer [ edit ] The Rhein-Flugzeugbau X-114 in flight. In Germany, Lippisch was asked to build a very fast boat for American businessman Arthur A. Collins. In 1963 Lippisch developed the X-112, a revolutionary design with reversed delta wing and T-tail. This design proved to be stable and efficient in ground effect and even though it was successfully tested, Collins decided to stop the project and sold the patents to a German company called Rhein Flugzeugbau (RFB), which further developed the inverse delta concept into the X-113 and the six seat X-114. These craft could be flown out of ground effect so that, for example, peninsulas could be overflown.[8] Hanno Fischer took over the works from RFB and created his own company, Fischer Flugmechanik, which eventually completed two models. The Airfisch 3 carried two persons, and the FS-8 carried six persons. The FS-8 was to be developed by Fischer Flugmechanik for a Singapore-Australian joint venture called Flightship. Powered by a V8 Chevrolet automobile engine rated at 337 kW, the prototype made its first flight in February 2001 in the Netherlands.[9] The company no longer exists but the prototype craft was bought by Wigetworks, a company based in Singapore and renamed as AirFish 8. In 2010, that vehicle was registered as a ship in the Singapore Registry of Ships.[10] The University of Duisburg-Essen is supporting an ongoing research project to develop the Hoverwing.[11] Gunther-Jörg-type tandem-airfoil flairboat [ edit ] A tandem flarecraft Skimmerfoil Jörg IV located at the SAAF Museum , Port Elizabeth, South Africa German engineer Günther Jörg, who had worked on Alexeyev's first designs and was familiar with the challenges of GEV design, developed a GEV with two wings in a tandem arrangement, the Jörg-II. It was the third, manned, tandem-airfoil boat, named "Skimmerfoil", which was developed during his consultancy period in South Africa. It was a simple and low-cost design of a first 4-seater tandem-airfoil flairboat completely constructed of aluminium. The prototype has been in the SAAF Port Elizabeth Museum since 4 July 2007, remained there till (2013) and is now in private use. Pictures of the museum show the boat after a period of some years outside the museum and without protection against the sun.[12] The consultancy of Dipl. Ing. Günther Jörg who was specialist and insider of German Airplane Industrie up from 1963 and a colleague of Alexander Lippisch and Hanno Fischer as well, was founded with a fundamental knowledge of Wing in ground effect physics, as well as results of fundamental tests under different conditions and designs having begun in 1960. During a period of more than 30 years Dipl. Ing. Gunther W. Jörg managed to built and fly successful a series of 15 different tandem-airfoil flairboats in different sizes and made of different materials. The following tandem-airfoil flairboat (TAF) types had been built after a previous period of nearly 10 years of research and development: TAB VII-3: First manned tandem W.I.G type Jörg, buing built at Technical University of Darmstadt, Akaflieg; TAF VII-5: Second manned tandem-airfoil Flairboat, 2 seater made of wood. TAF VIII-1: 2-seater tandem-airfoil flairboat built of GRP / Aluminium. A small serie of 6 Flairboats had been produced by former Botec Company. TAF VIII-2: 4-seater tandem-airfoil Flairboat built of full aluminium (2 units) and built of GRP (3 Units) TAF VIII-3: 8-seater tandemIrfoil Flairboat built of aluminium combined with GRP parts. TAF VIII-4: 12-seater tandem Airfoil Flairboat built of aluminium combined with GRP parts as well. TAF VIII-3B: 6-seater tandem-airfoil flairboat under carbon fibre composite construction. Bigger concepts are: 25-seater, 32-seater, 60-seater, 80-seater and bigger up to the size of a passenger airplane. All those tandem-airfoil flairboats are registered as motorboat and classified as type A WIG. In 1984, Gunther W. Jörg was decorated with "Philip Morris Award" for future transportation. In 1987, the Botec Company was founded. After his death in 2010 business is continued by his daughter and former assistant Ingrid Schellhaas with her company Tandem WIG Consulting. Since the 1980s [ edit ] GEVs developed since the 1980s have been primarily smaller craft designed for the recreational and civilian ferry markets. Germany, Russia and the United States have provided most of the momentum with some development in Australia, China, Japan, Korea and Taiwan. In these countries and regions, small craft up to ten seats have been designed and built. Other larger designs as ferries and heavy transports have been proposed, but have not been carried to fruition. Besides the development of appropriate design and structural configuration, special automatic control systems and navigation systems are also being developed. These include special altimeters with high accuracy for small altitude measurements and also lesser dependence on weather conditions. After extensive research and experimentation, it has been shown that "phase radio altimeters" are most suitable for such applications as compared to laser altimeter, isotropic or ultrasonic altimeters.[13] With Russian consultation, the United States Defense Advanced Research Projects Agency (DARPA) studied Aerocon's 170-metre long (550-foot) wingship.[14][15][16][17][18][19] A Hoverwing Universal Hovercraft developed a flying hovercraft, a prototype of which first took flight in 1996.[20] Since 1999, the company has offered plans, parts, kits and manufactured GEV hovercraft called the Hoverwing.[21] In Singapore, Wigetworks has continued development and obtained certification from Lloyd's Register for entry into class.[22] On 31 March 2011 AirFish 8-001 became one of the first WIG to be flagged with the Singapore Registry of Ships, one of the largest ship registries.[23] Wigetworks has also partnered with National University of Singapore's Engineering Department to develop higher capacity WIG craft.[24] In Korea, Wing Ship Technology Corporation has developed and tested a 50-seat passenger version of a WIG craft named the WSH-500.[25] Iran deployed three squadrons of Bavar 2 two-seat GEVs in September, 2010. This GEV carries one machine gun and surveillance gear, and incorporates features which reduce its radar signature in a similar manner to stealth.[26] In October 2014, satellite images showed new images of the Ekranoplan in a shipyard in south of Iran. The Ekranoplan has two engines and no armament.[27] The designers Burt Rutan in 2011[28] and Korolev in 2015 have shown ekranoplan projects.[29] Estonian transport company Sea Wolf Express plans to launch passenger service in 2019 between Helsinki and Tallinn, a distance of 87 km taking only half an hour, using a Russian-built ground effect vehicle (GEV).[30] The company has ordered 15 GEVs with maximum speed of 185 km/h and capacity of 12 passengers and they are built by Russian RDC Aqualines.[31] See also [ edit ] Notes [ edit ] ^ Cl/da, with Cl = lift coefficient, and a = angle of incidence. ^ Not a stabilizer because destabilizing. Citations [ edit ] Bibliography [ edit ]
– Most people who've slammed rum and vodka drinks all night end up in slurred conversations about the meaning of life, drunk texting, or just passing out. But a second-year student at Michigan Technological University says he witnessed his trashed roommate do something a little more unusual late Saturday: design an entire aircraft, with no memory of it in the morning, the Guardian reports. Keith Fraley, 19, tells the paper that "Mark" (who doesn't want to use his real name in case future employers don't approve of his drinking adventures) stumbled into their room at about 11:30pm to grab some textbooks, returning minutes later for his whiteboard. Around 1:30am he was back, rambling "like a slurred robot" about his creation, which he described as an ekranoplan, a "ground effect" vehicle that hovers over water. The guys Mark was drinking with as he "frantically" whipped up his aerospace math calculations tell Fraley that Mark was "very intoxicated" and "was passing out on his whiteboard from time to time" as he worked. Amazingly, Mark says he can't recall a thing: He woke up the next morning "basically questioning his sanity because of the immense amount of work that was in front of him," Fraley says. The tweet Fraley sent out about his roomie's feat—in which he marvels, "so my roommate came back drunk last night and doesnt remember designing an entire f---ing airplane"—has also taken off, with more than 81,000 retweets and 133,000 favorites so far. Responses range from critiques of the design to admiration to outright envy, with one commenter tweeting, "I need to know WTF he was drinking!!" But would the aircraft actually function? Fraley tells the Guardian: "Mark says ... he looks forward to trying to re-create his work into a remote-control model with his colleagues." (Maybe a wasted engineer designed this "evil" airplane seat.)
treatment of systemic fungal infections often requires from weeks to months of drug therapy . consistently medicating companion animals for this length of time can be difficult and even more so with animals that become stressed with handling , such as wildlife or exotic pets . nondomesticated animals are susceptible to stress from repeated handling and restraint , and stress can lead to the death of hospitalized wildlife or exotic pets . stress , including that associated with handling in animals , has also been shown to lead to immunosuppression and increased susceptibility to disease . therefore , stress associated with repeated handling for treatment of an infection could inhibit an animal 's ability to mount an appropriate immune response [ 24 ] . white nose syndrome , caused by the fungus geomyces destructans , is an infection that affects insectivorous bats of north america [ 57 ] . extremely high mortality rates are associated with infection and to date , no effective treatments have been found . if numbers of bats continue to decline and approach extinction , members of various affected species may need to be captured and kept in captivity in order to preserve genetic diversity for eventual release and repopulation . animals may be infected with g. destructans when captured and need antifungal treatment that is long acting and which would require limited handling of the animal . terbinafine is a fungicidal medication that inhibits the synthesis of ergosterol which is an essential component of fungal walls . although no studies examining this drug in bats have been published , studies have been performed in other animal species [ 812 ] . geomyces pannorum , a fungus that is closely related to g. destructans , can cause infection in humans and is susceptible to terbinafine [ 13 , 14 ] ; no published reports regarding the sensitivity of g. destructans to terbinafine are available . geomyces destructans has been shown to be susceptible to other antifungal agents in vitro including fluconazole , but terbinafine has a better safety profile than many other commonly used antifungal medications [ 1618 ] . the goal of this study was to investigate a terbinafine impregnated implant designed for subcutaneous placement over the dorsum of bats infected with g. destructans ; the in vitro release of terbinafine from the implant was evaluated at two different temperatures , 4c and 37c , over the course of approximately 6 months . the two temperatures were chosen because they are similar to the body temperatures of hibernating ( 4c ) and nonhibernating ( 37c ) bats . this initial trial was designed to determine if terbinafine would release from the implant over the course of many months without degradation of the implant in an in vitro setting . implants were constructed by melatek , llc ( madison , wi , usa ) based on protocols used to make ferretonin implants . these implants are stable for approximately 5 years if kept at 4c ( t. cairns , pers . louis , mo , usa ) was mixed with medical grade elastomer to a calculated concentration so that each implant would contain 0.5 mg of terbinafine . the mixture was placed into a mold where it cured and was then cut into individual implants . each implant was approximately the size of a passive integrated transponder ( pit ) tag ( microchip ) as shown in figure 1 . cured medical grade elastomer is dimensionally and thermally stable , resistant to oxidation and sunlight , and does not become hard with age ( t. cairns , pers . comm . ) . implants were kept at 4c for approximately one month according to manufacturer instructions prior to placement into saline . for in vitro analysis , implants were individually placed into 25 ml of isotonic saline in glass containers . every 7 days , the solution in each container was mixed to ensure homogeneity and 350 l was then removed and placed into a cryo - tube for analysis . following sample removal , isotonic saline ( 350 l ) was added to the container so the volume was kept consistent . samples were collected for a total of 28 weeks and were kept in a 80c freezer until analysis . the system consisted of a 2695 separations module , a 2487 absorbance detector ( waters , milford , ma , usa ) . terbinafine was extracted from saline samples using a hexane extraction and was separated on a symmetry shield c18 ( 4.6 100 mm , 5 m ) column with a guard column . the mobile phase was a mixture of ( a ) 20 mm phosphoric acid with 0.1% triethylamine adjusted to ph 3.0 and ( b ) acetonitrile ( 65 : 35 ) . standard curves for analysis were prepared by fortifying saline with terbinafine to produce a linear concentration range of 51500 ng / ml . average recovery for terbinafine was 95% while intra- and interassay variability were less than 10% . the lower limit of quantification was 5 ng / ml . following hplc analysis , the mean release of terbinafine with standard deviations was calculated for the different temperatures at each time point . if the values were normally distributed , a t - test was performed to determine if a significant difference in amount of terbinafine released was present at the two temperatures . if the data was not normally distributed , a mann - whitney / wilcoxon two - sample test was used to determine if differences existed . significance was set at p < 0.05 and analysis was performed with epiinfo ( cdc , atlanta , ga , usa ) . samples were collected and analyzed with hplc for a total of 28 weeks after initial placement into isotonic saline . a sample was not collected during week 23 . the mean amount released from the implants at the two different temperatures during the 28 weeks the amount released from the implants at 37c was significantly greater than 4c at the 1 ( p < 0.01 ) , 17 ( p < 0.01 ) , 26 ( p = 0.03 ) , and 28 ( p = 0.04 ) week time points ; the amount released from implants at 4c was greater than 37c at the 2 ( p = 0.04 ) and 3 ( p = 0.02 ) week time points . the mean amount of terbinafine released weekly across the 28 weeks was approximately 1.7 g at 4c and 4.3 g at 37c . the implant was evaluated at two different temperatures because of the differing rates of metabolism between hibernating and nonhibernating bats . it was hypothesized that more terbinafine would be released at 37c than at 4c . if terbinafine was released from implants at different rates at the different temperatures , excessively high concentrations may be reached in nonhibernating bats or suboptimal concentrations may be reached in hibernating bats . in this study , there were significant differences between the release rates at 6 of the time points , but the levels were not consistently higher at one temperature compared to the other . variations in the amount of drug released from the implants occurred at both temperatures and led to large standard deviations at some time points . this variation in drug release may have been due to slight differences in the temperature within the incubator / refrigerator or from incomplete mixing of the solution prior to sampling . additionally , the measured concentrations at some time points indicated that the release was negative . these values may have been due to little if any release following the previous sample collection and replacement with saline which led to an overall lower concentration in the container . terbinafine has been used in refractory fungal infections with success and typically has fewer adverse effects than other antifungal medications . unpublished research has shown that g. destructans is susceptible to terbinafine , but minimum inhibitory concentrations ( mic ) are not available . in vitro susceptibility of other fungi and yeasts ranges from 0.001 to 128.0 g / ml . the mean amount of terbinafine released weekly during the 28 weeks was 1.7 g at 4c and 4.3 g at 37c . assuming the typical little brown bat ( myotis lucifugus ) weighs approximately 10 grams and this in vitro test is an appropriate approximation of the amount of terbinafine that would be released in vivo , bats would have a circulating concentration ranging from 0.02 to 0.06 g / ml for approximately 6 months depending on body temperature . these circulating concentrations would fall within the mic for many pathogenic fungi and yeast , however , further studies are needed to determine the mic of g. destructans . additionally , initial clinical trials in little brown bats are currently being performed ( m. souza , pers . implants were placed subcutaneously over the dorsum of bats infected with g. destructans and safety and efficacy of the implants will be determined . results are not yet available , but skin samples will be evaluated with hplc to determine terbinafine concentrations . in conclusion , terbinafine was released from the implant over the course of 6 months with no consistent significant differences at two different temperatures , 37c and 4c . however , without in vivo absorption , metabolism and clearance , it is difficult to know whether this implant will release therapeutic amounts of terbinafine in g. destructans infected bats . this research was the first step to determine if terbinafine would release from the implant over an extended period of time and what amounts might be released . future research will need to examine the implants in animals to determine the concentration of systemic terbinafine over time . following further investigation , this implant may provide a long term treatment for g. destructans infected bats that requires handling only once at the beginning of treatment .
a terbinafine impregnated subcutaneous implant was evaluated to determine if drug was released into isotonic saline over the course of 6 months at two different temperatures , 37c and 4c . these temperatures were chosen to simulate the nonhibernating ( 37c ) and hibernating body ( 4c ) temperatures of little brown bats ( myotis lucifugus ) . insectivorous bats of north america , including little brown bats , have been devastated by white nose syndrome , a fungal infection caused by geomyces destructans . no treatments exist for bats infected with g. destructans . implants were placed into isotonic saline ; samples were collected once per week and analyzed with hplc to determine terbinafine concentrations . the mean amount of terbinafine released weekly across the 28 weeks was approximately 1.7 g at 4c and 4.3 g at 37c . although significant differences in the amount released did occur at some time points , these differences were not consistently greater or less at either of the temperatures . this study showed that terbinafine was released from an impregnated implant over the course of 6 months at concentrations ranging from 0.02 to 0.06 g / ml depending on temperature , which may be appropriate for little brown bats ( myotis lucifugus ) infected with geomyces destructans , the etiologic agent of white nose syndrome .
tissue engineering ( te ) provides a therapeutic alternative to organ transplantation , bypassing issues of immunosuppression and organ shortage . te has recently had successful applications in the clinic , with replacement of organs such as the bladder , urethra and trachea , both in adults and children . building a tissue - engineered organ a scaffold can be prepared using naturally - derived ( e.g. collagen ) and synthetic ( e.g. poly - l - glycolic acid ; plga ) materials , or be obtained by the decellularization of native organs and tissues . scaffolds that have been used thus far for intestinal te have mainly been either decellularized ( small intestinal submucosa ) or synthetic ( poly - l - glycolic acid and poly - lactic acid ) . these biomaterials are very simple in both macro- and micro - architecture , which may not be ideal if tissue - engineered intestine is to be clinically translated . an optimal biomaterial for the intestine should have an innate vascular tree that can be connected to the host 's blood supply , a tiered tubular wall with different properties to reflect the layers of the intestinal wall and a villus - crypt axis on the luminal side to aid with repopulation by epithelial stem cells . decellularization is a novel methodology that produces scaffolds by removing cells from whole organs whilst maintaining their original architecture . this is preferable to already existing scaffolds since they do not only replicate the structure of the organ but also contain chemical cues embedded within the extracellular matrix ( ecm ) that aid cellular proliferation and differentiation . in 2008 a cadaveric trachea was decellularized , seeded with the patient 's own cells , and transplanted to replace the main left bronchus in a young man . since then , a number of groups have reported the production of decellularized scaffolds for the heart , liver , and lung in small and large animals . the goal of the method described herein is to produce decellularized intestinal matrices that maintain the macroscopic characteristics of the original tissue such as the blood supply , as well as the microscopic architecture of the villus - crypt axis in the intestinal lumen . we believe this methodology could ultimately be adopted for other organs to improve the efficiency of decellularization . prepare a 1 l solution of phosphate buffered saline ( sigma , uk ) with 1% antibiotic / antimycotic ( sigma , uk ) ( pbs / aa ) . fit the peristaltic pump ( masterflex l / s variable speed ) with two tubes . run 70% ethanol ( etoh ) through the tubes of the peristaltic pump for 15 min at maximum speed , followed by pbs / aa for another 15 min . euthanize adult sprague - dawley rats weighing approximately 250 - 350 g by co2 inhalation and cervical dislocation in accordance with local animal guidelines and approvals ( in the uk , home office guidelines under the animals ( scientific procedures ) act 1986 ) . spray and wipe the abdomen of the animal using 70% etoh . perform a xifo - pubic laparotomic incision on the abdomen to ensure a clear surgical field . eviscerate the small intestine on the right side of the animal onto a paper towel sprayed with 70% etoh . take care to continuously wet the intestine with pbs / aa so as to avoid dehydration of the tissue and denaturation of the extracellular matrix ( ecm ) . locate the superior mesenteric artery ( sma ) arising in a 90 angle from the aorta towards the intestine . use a 27 g cannula to enter the sma from the aorta and quickly withdraw the needle to avoid tearing the wall of the vessel . advance the plastic tube of the cannula into the sma and secure using sutures ( vicryl 5/0 ) . use spring scissors to incise the aorta proximal and distal to the sma so as to release the cannula . to avoid leakage of feces when dissecting out the large intestine , place one ( silk 5/0 ) suture knot on the proximal end of the ileocaecal junction and one at the distal end of the sigmoid colon . then cut the terminal ileum and colon between the two knots and remove the large intestine . cut the intestine at the jejuno - duodenal junction and free the intestine from any connective tissue connections it might have with the abdomen . transfer the small intestine in a petri dish with pbs / aa . cannulate the proximal section of the intestine with a plastic pasteur pipette ( lsl laboratory consumables ) and secure it in place with sutures . cut the pipette so it will fit the luer - lok of a 60 ml syringe ( bd plastipak ) . flush the intestinal lumen 2x with 60 ml of pbs / aa to remove feces and debris . this will ease handling , minimize tension on the vascular tree and allow removal of bubbles from the tubing . start running deionized water ( resistivity 18.2 m/cm ) through the masterflex l / s variable speed roller pump at 0.6 ml / hr . ensure no bubbles are present within tubing prior to connecting with the intestinal lumen stopcock . some bubbles may be present within the lumen from step 1.9 , which may impair the decellularization process . vary the speed of the pump and handle the tissue with forceps carefully to ensure the bubbles exit from the distal end . do not connect the vascular cannula until this process is finished since high speeds may damage the vascular tree . transfer apparatus to the cold room , since the following step of decellularization is performed at 4 c . perfuse both the intestinal lumen and the vascular tree with deionized water ( resistivity 18.2 m/cm ) for 24 hr at 0.6 ml / hr . for the first hour check the apparatus regularly to ensure all connections are secure , leakage is minimal and no bubbles are present within the intestine . after 24 hr of treatment with deionized water , move decellularization apparatus outside the cold room as the rest of the steps are carried out in room temperature ( rt ) . weigh sodium deoxycholate ( sigma , uk ) to prepare 300 ml of a 4% solution in deionized water . weigh sodium deoxycholate under a suction hood , as it is an oral and eye irritant . change the deionized solution to sodium deoxycholate , check the connections , remove any bubbles and perfuse at 0.6 ml / hr for 4 hr . following the sodium deoxycholate step wash with pbs / aa for 30 min to avoid interaction between the sodium deoxycholate and dnase - i . weigh out deoxyribonuclease - i ( dnase - i , sigma ) and prepare 250 ml of a 2,000 ku solution in 1 m sodium chloride , ph 7.4 . wash with pbs / aa for 30 min to ensure all remnants of the decellularization solutions are removed . place the scaffold in a new petri dish and transfer to a uv crosslinker ( spectroline , us ) . run two sterilization cycles . store in 5% pbs / aa and change the solution every 3 days . prepare a 1 l solution of phosphate buffered saline ( sigma , uk ) with 1% antibiotic / antimycotic ( sigma , uk ) ( pbs / aa ) . fit the peristaltic pump ( masterflex l / s variable speed ) with two tubes . run 70% ethanol ( etoh ) through the tubes of the peristaltic pump for 15 min at maximum speed , followed by pbs / aa for another 15 min . euthanize adult sprague - dawley rats weighing approximately 250 - 350 g by co2 inhalation and cervical dislocation in accordance with local animal guidelines and approvals ( in the uk , home office guidelines under the animals ( scientific procedures ) act 1986 ) . spray and wipe the abdomen of the animal using 70% etoh . perform a xifo - pubic laparotomic incision on the abdomen to ensure a clear surgical field . eviscerate the small intestine on the right side of the animal onto a paper towel sprayed with 70% etoh . take care to continuously wet the intestine with pbs / aa so as to avoid dehydration of the tissue and denaturation of the extracellular matrix ( ecm ) . locate the superior mesenteric artery ( sma ) arising in a 90 angle from the aorta towards the intestine . use a 27 g cannula to enter the sma from the aorta and quickly withdraw the needle to avoid tearing the wall of the vessel . advance the plastic tube of the cannula into the sma and secure using sutures ( vicryl 5/0 ) . use spring scissors to incise the aorta proximal and distal to the sma so as to release the cannula . to avoid leakage of feces when dissecting out the large intestine , place one ( silk 5/0 ) suture knot on the proximal end of the ileocaecal junction and one at the distal end of the sigmoid colon . then cut the terminal ileum and colon between the two knots and remove the large intestine . cut the intestine at the jejuno - duodenal junction and free the intestine from any connective tissue connections it might have with the abdomen . transfer the small intestine in a petri dish with pbs / aa . cannulate the proximal section of the intestine with a plastic pasteur pipette ( lsl laboratory consumables ) and secure it in place with sutures . cut the pipette so it will fit the luer - lok of a 60 ml syringe ( bd plastipak ) . flush the intestinal lumen 2x with 60 ml of pbs / aa to remove feces and debris . this will ease handling , minimize tension on the vascular tree and allow removal of bubbles from the tubing . start running deionized water ( resistivity 18.2 m/cm ) through the masterflex l / s variable speed roller pump at 0.6 ml / hr . ensure no bubbles are present within tubing prior to connecting with the intestinal lumen stopcock . some bubbles may be present within the lumen from step 1.9 , which may impair the decellularization process . vary the speed of the pump and handle the tissue with forceps carefully to ensure the bubbles exit from the distal end . do not connect the vascular cannula until this process is finished since high speeds may damage the vascular tree . transfer apparatus to the cold room , since the following step of decellularization is performed at 4 c . perfuse both the intestinal lumen and the vascular tree with deionized water ( resistivity 18.2 m/cm ) for 24 hr at 0.6 ml / hr . for the first hour check the apparatus regularly to ensure all connections are secure , leakage is minimal and no bubbles are present within the intestine . after 24 hr of treatment with deionized water , move decellularization apparatus outside the cold room as the rest of the steps are carried out in room temperature ( rt ) . weigh sodium deoxycholate ( sigma , uk ) to prepare 300 ml of a 4% solution in deionized water . weigh sodium deoxycholate under a suction hood , as it is an oral and eye irritant . change the deionized solution to sodium deoxycholate , check the connections , remove any bubbles and perfuse at 0.6 ml / hr for 4 hr . following the sodium deoxycholate step wash with pbs / aa for 30 min to avoid interaction between the sodium deoxycholate and dnase - i . weigh out deoxyribonuclease - i ( dnase - i , sigma ) and prepare 250 ml of a 2,000 ku solution in 1 m sodium chloride , ph 7.4 . perfuse with dnase - i for 3 hr at rt at a speed of 0.6 ml / hr . following the dnase - i step , transfer the scaffold into a tissue culture hood and change plates and instruments . wash with pbs / aa for 30 min to ensure all remnants of the decellularization solutions are removed . place the scaffold in a new petri dish and transfer to a uv crosslinker ( spectroline , us ) . run two sterilization cycles . store in 5% pbs / aa and change the solution every 3 days . upon successful decellularization ( figure 1 ) , the scaffold should have a macroscopic appearance similar to the one of the native intestine , but with translucent walls ( figure 2a ) . the preservation of macro - architecture should also be evident by the patency of the vascular tree . when dye is injected through the sma cannula , it should distribute evenly throughout the scaffold and reach the capillary tree ( figure 2b ) . the scaffold should be free of nuclear and cytoplasmic material , something that can be assessed using a dna quantification kit and simple histological analysis . hematoxylin and eosin staining ( h&e ) should demonstrate an absence of nuclear and cytoplasmic material whilst preserving the small intestinal layers ( figure 3a ) . in particular , the maintenance of the villi and crypts on the luminal side should be evident following scanning electron microscopy ( figure 4 ) . a conservation of extracellular matrix components such as collagen , elastin and glycosaminoglycans should also be expected . for example , masson 's trichrome staining displays intact connective tissue in the scaffold ( figure 3b ) . timeline of decellularization procedure ; pbs / aa : phosphate buffered saline with antibiotic - antimycotic , nadeoxy : sodium deoxycholate , rt : room temperature , dnase - i : deoxyribonuclease - i . injection of rosso ponceau dye through the sma demonstrates an intact vascular network ( b ) ; sma : superior mesenteric artery click here to view larger image . h&e ( a ) and mt ( b ) staining indicate an absence of cellular material with preservation of the connective tissue architecture ; h&e : hematoxylin and eosin , mt : masson 's trichrome . scanning electron microscopy indicates the preserved villus - crypt architecture in the scaffold lumen ; scale bar : 100 m . the most difficult steps in setting up this experiment involve the cannulation of the sma and the establishment and maintenance of sterility . cannulating the sma in rodents without rupturing the wall can be quite difficult due to the size and position of the vessel . alternatively , a suture may be placed around the proximal aorta prior to the sma origin , followed by cannulation of the aorta itself distally , directing the plastic cannula into the sma . during decellularization a combination of poor cannula placement and high flow rates may result in losing the vascular access . sterility is a major issue due to the amount of bacterial flora present in the small intestine . washing with pbs / aa following harvest is very important , and any sign of fecal matter or debris must be removed from the lumen . placing a portion of the scaffold in a falcon tube with dmem in the incubator following uv sterilization should be an indicator if sterility has been achieved . in the case of bacterial colonization , the media will change the ph with its color turning from red to yellow . to deal with this , further uv cycles are advised as well as washing with pbs containing a high concentration of antibiotic / antimycotic . a possible modification to obtain a scaffold with both vascular and venous access would be to cannulate the inferior vena cava ( ivc ) as well as the sma . decellularization from the venous and vascular sides should be attempted intermittently for all three solutions . continuous decellularization may burst the capillaries by having positive pressure on both sides . over the years there have been a number of efforts in intestinal te using different cell - scaffold combinations in vitro and in vivo . the majority of the work has been performed using tubular nonwoven 95% pga-5% plga scaffolds coated with collagen type i. following seeding with intestinal epithelial organoid units ( ous ) and a period of implantation into the omentum of mice , they form cysts with muscle on the outside and epithelium on the inside which can then be tubularized . however , the porosity and simplicity in the design of these scaffolds does not permit for the generation of large pieces of artificial intestine in an in vitro environment such as that of a bioreactor . additionally , the lack of an innate vascular network that can be connected to the recipient further limits the use of this scaffold for clinical translation . besides the experiments with the pga - plga scaffolds , other groups have used collagen or sis scaffolds , both of which do not replicate the intricacy of the intestinal tract . sis in particular is the only previous published methodology of intestinal tissue engineering and has been used in more than 150 medical settings , demonstrating the ability of decellularized scaffolds to provide mechanical stability and promote cell growth whilst leading to no immunogenic response . however , the lack of appropriate macro- and micro - architecture , has led to poor results in its ' use for intestinal te purposes . the benefits of the decellularization methodology we have described include the preservation of microscopic characteristics such as the luminal crypt - villus architecture that represent an appropriate environment for the repopulation by the intestinal stem cell niche . in the macroscopic aspect , the presence of a hierarchical vascular network will enable attachment to the recipient , allowing provision of nutrients and oxygen to all layer of the te - intestine . what is more , the maintenance of ecm components such as collagen , elastin and glyocosaminoglycans has an important role not only for mechanical characteristics but also directing cellular proliferation and differentiation . most importantly , the ability of the decellularization methodology to be scaled up into larger tissues whilst maintaining the same characteristics is an important feature for clinical translation of te . the development of a natural intestinal matrix with a vascular network allows the creation of larger segments of artificial intestine that can be connected to the host .
successful tissue engineering involves the combination of scaffolds with appropriate cells in vitro or in vivo . scaffolds may be synthetic , naturally - derived or derived from tissues / organs . the latter are obtained using a technique called decellularization . decellularization may involve a combination of physical , chemical , and enzymatic methods . the goal of this technique is to remove all cellular traces whilst maintaining the macro- and micro - architecture of the original tissue.intestinal tissue engineering has thus far used relatively simple scaffolds that do not replicate the complex architecture of the native organ . the focus of this paper is to describe an efficient decellularization technique for rat small intestine . the isolation of the small intestine so as to ensure the maintenance of a vascular connection is described . the combination of chemical and enzymatic solutions to remove the cells whilst preserving the villus - crypt axis in the luminal aspect of the scaffold is also set out . finally , assessment of produced scaffolds for appropriate characteristics is discussed .
conventional optical surveys of supernova remnants ( snrs ) use the criterion [ ] /h@xmath1 @xmath6 ( e.g. , * ? ? ? * ) , because the [ ] @xmath76717 , 6731 doublet emission is strong in the cooling zone behind snr shocks . in the large magellanic cloud ( lmc ) , a number of large shell nebulae were reported to have [ ] /h@xmath1 ratios @xmath80.5 and even as high as 1.0 @xcite , but their nature as snrs could not be confirmed . two of these [ ] -bright shell nebulae , lha 120-n70 and lha 120-n185 ( n70 and n185 for short ; * ? ? ? * ) , are particularly intriguing because of their extremely filamentary shell morphologies and high [ ] /h@xmath1 ratios in parts of their shell rims . n70 is also known as deml301 and n185 as deml25 @xcite . the arguments against the snr hypothesis for n70 include the following : ( 1 ) its @xmath0100 pc diameter is much larger than those of known snrs ; ( 2 ) its radio spectral index ( @xmath9 , * ? ? ? * ; @xmath10 , * ? ? ? * ; @xmath11 , * ? ? ? * ) is more in accord with thermal than nonthermal emission ; and ( 3 ) its expansion velocity is much lower than those of snrs . furthermore , n70 encompasses the ob association lh114 @xcite , and thus n70 could be a superbubble blown by the fast stellar winds and supernovae ( sne ) from lh114 . the strongest argument for the existence of sn explosion in n70 is the detection of diffuse x - ray emission by the _ einstein x - ray observatory_. as the diffuse x - ray luminosity of n70 is higher than that expected from a quiescent superbubble , it is suggested that n70 is a superbubble experiencing additional heating by recent sne in the shell interior @xcite . in an optical study , the h@xmath1 , [ ] , [ ] , and [ ] images of n70 have been used to analyze the nebular morphology and excitation , and it is concluded that the stellar population in lh114 provides more ionizing radiation than needed and that the high [ ] /h@xmath1 ratios may result from low - velocity shocks @xcite . n185 is also large , 125@xmath12100 pc . it contains no cataloged ob associations @xcite , while one late - o and eight early - b stars are projected within its boundary @xcite . its expansion velocity , measured with fabry perot interferograms , is @xmath270 kms@xmath4 , similar to that of n70 measured with the same instrument . the radio emission of n185 , with a spectral index of @xmath13 , is apparently nonthermal @xcite . both _ einstein _ and _ rosat _ observations of n185 show a hint of diffuse x - ray emission that needs to be confirmed by deeper x - ray observations . n185 has been suggested to be a snr that is now photoionized by the blue stars within . to critically examine the physical nature of n70 and n185 , we have acquired _ xmm - newton _ x - ray observations and high - dispersion long - slit spectroscopic observations of these two shell nebulae . in this paper , we describe the observations in section 2 , analyze the physical properties of the hot gas in n70 and n185 in sections 3 and 4 , respectively , and discuss the origin of the hot gas in section 5 . we have obtained _ xmm - newton _ x - ray observations and high - dispersion long - slit spectra of the h@xmath1 and [ ] lines of n70 and n185 . to complement the analysis of distribution and spectral properties of the diffuse x - ray emission from the shells , we have also used observations and optical images . our _ xmm - newton _ observations of n70 were performed on 2008 january 2627 ( obsid : 0503680201 ; pi : williams ) for 41.9 ks , and n185 on 2008 march 1011 for 42.4 ks ( obsid : 0503680101 ; pi : williams ) . both sets of observations were made in the full frame mode with the thin filter . three european photon imaging cameras ( epic ) , pn , mos1 , and mos2 , were used for the photon energy range of 0.1515 kev . each camera has a field of view of @xmath230@xmath14 and an on - axis angular resolution of @xmath26@xmath15 . the epic data were reprocessed with the science analysis system software version 11.0.0 and the _ xmm - newton _ extended source analysis software ( _ xmm_-esas ) package . after removing bad events and intervals of high background flares , the effective exposure times of the epic mos1 , mos2 , and pn are 23.7 , 18.7 , and 10.9 ks for n70 , and 8.1 , 8.3 , and 4.8 ks for n185 , respectively . the quiescent particle background , soft proton contaminations , and exposure maps were all corrected using the _ xmm_-esas package . finally , point sources were detected and excised , and the resultant maps of the diffuse x - ray emission were adaptively smoothed . the mos1 , mos2 , and pn combined images in the 0.40.7 , 0.71.0 , and 1.01.3 kev bands are shown in figure [ figure1 ] for n70 , and in figure [ figure2 ] for n185 . to extract spectra from the epic observations , we define the source and background regions as shown in figure [ figure3 ] . because of the small number of counts detected , a single source region is selected to include all diffuse emission in each object : the source region of n70 encompasses its entire shell , and the source region of n185 encompasses both the entire shell and the blowout . in order to minimize the instrumental background , the background region is selected to be on the same ccd as the source region . the total background - subtracted counts in mos1 , mos2 , and pn are 1141 , 1182 , and 2731 for n70 , and 295 , 240 , and 272 for n185 , respectively . in the case of n185 , the numbers of counts are small , thus the mos1 and mos2 data are combined to extract a spectrum . the background - subtracted spectra are then adaptively binned to achieve a signal - to - noise ratio ( s / n ) of at least 3 . the analysis and model fits to these spectra are described later in sections 3.2 and 4.2 . both n70 and n185 were observed with the echelle spectrograph on the blanco 4 m telescope at cerro tololo inter - american observatory ( ctio ) . the observations were made in a long - slit , single - order mode , in which a broad h@xmath1 filter was used and a flat mirror replaced the cross dispersor , resulting in a coverage of the h@xmath1 and [ ] @xmath76548 , 6584 lines over a slit length of @xmath16 . a 79 lines mm@xmath4 echelle grating was used . n70 was observed on 1986 november 22 and 1988 january 11 . the air schmidt camera and a gec 385@xmath12576 ccd were used to record data ; the 22 @xmath17 m pixel size corresponded to 0635 along the slit and @xmath20.21 along the dispersion . a slit width of 165 was used and the resultant instrumental fwhm was 21@xmath181 kms@xmath4 at the h@xmath1 line . two consecutive east west slit positions were observed in 1986 @xcite and a north south slit position was observed in 1988 . the long - slit echelle spectra are shown in figure [ figure4 ] with slit positions marked on an h@xmath1 image of n70 . n185 was observed on 1995 january 20 . the red long focus camera and a tek 2048 @xmath12 2048 ccd were used to record data ; the 24 @xmath17 m pixel size corresponded to 0267 along the slit and 0.082 along the dispersion . a 165 slit width was used and the instrumental fwhm was @xmath214 kms@xmath4 at the h@xmath1 line . only one east west slit position was observed . the long - slit echelle image and the slit position on an h@xmath1 image of n185 are shown in figure [ figure5 ] . the echellograms in figures 4 and 5 show very different velocity structures between n70 and n185 . n70 shows mostly unsplit line with centroid velocity variations within the range of @xmath19 = 280340 km s@xmath4 ; only the western part of n70 ( relative position 60@xmath15150@xmath15 along the east west slit ) show a velocity split of @xmath270 km s@xmath4 . from these velocity structures , we can conclude that the shell of n70 can not be expanding faster than 35 km s@xmath4 . ( note that the center of expansion is not the geometric center of n70 ; therefore , no geometric correction is needed for the local expansion velocity . ) in contrast , n185 shows velocity splits throughout the slit length , consistent with a global expansion . the receding side of n185 is detected at velocities from @xmath19 = 260 to 320 km s@xmath4 with additional high - velocity features reaching @xmath20 420 km s@xmath4 , while the approaching side is detected at @xmath19 = 220180 km s@xmath4 . in addition to these approaching and receding components of the n185 shell , there is a stationary component at @xmath19 @xmath2 250 km s@xmath4 , which can either be an irrelevant line - of - sight component or associated with the ambient medium of n185 . the systemic velocity of n185 is most likely in the range of @xmath19 = 240250 km s@xmath4 , considering the centroid velocity at the shell rim and the stationary component . the bulk expansion velocity of n185 is thus at least @xmath270 km s@xmath4 and expansion velocities up to @xmath2200 km s@xmath4 are present in certain parts of the nebula . therefore , we will adopt an expansion velocity of @xmath2135 km s@xmath4 for n70 and @xmath070 km s@xmath4 for n185 . the velocity structures of n70 and n185 determined from our echelle data are at odds with previous studies using fabry perot interferograms , which reported expansion velocities of 70 km s@xmath4 for both n70 and n185 . these differences can be explained by the deficiencies of fabry perot interferograms : ( 1 ) the velocity information in fabry perot interferograms can be erroneously modulated by the nebula s surface brightness , and this is particularly problematic for narrow filaments that do not fill the entire width of an interference fringe ; ( 2 ) the limited free spectral range ( fsr ) causes aliasing among velocity components whose velocity differences are multiples of the fsr ; and ( 3 ) the interferograms were recorded through an image tube onto photographic plates , which are not as sensitive as ccds . in the case of n70 , the interferograms show that line splits are only seen in localized regions ( figure 1 of rosado et al . 1981 ) , consistent with our echelle observations ; however , their expansion velocity of 70 km s@xmath4 was based on an optimistic fit of a velocity - radius ellipse to data points that clearly do not represent a hollow expanding shell ( figure 3 of rosado et al . 1981 ) . in the case of n185 , the 100 km s@xmath4 fsr of the interferogram precludes the detection of high - velocity features that are clearly detected in our long - slit echelle observations ; therefore , the highest possible expansion velocity reported by corresponds to our lower limit of n185 s expansion velocity . optical images of n70 and n185 are available from the magellanic cloud emission line survey ( mcels ; smith and mcels team 1999 ) . the [ ] images are useful in showing high - excitation regions and the [ ] images reveal ionization fronts as well as cooling regions behind shocks . the mcels images have an angular resolution of @xmath22@xmath15 . for a higher angular resolution ( @xmath2110 ) , we use our h@xmath1 images of n70 and n185 taken with the mosaic ii camera on the ctio blanco 4 m telescope . to examine the distribution of in the vicinity of n70 and n185 , we use the 21 cm line data cube of the lmc made with combined australia telescope compact array observations and parkes single - dish observations @xcite . both the column density map and iso - velocity maps are compared with the surface brightness variations of the diffuse x - ray emission in and around n70 and n185 to assess the distributions of foreground absorption ( see sections 3.1 and 4.1 ) . n70 is a faint diffuse x - ray source . to examine the spatial distribution of its x - ray emission , we extract images in the 0.40.7 , 0.71.0 , and 1.01.3 kev bands , avoiding 1.41.8 kev due to the instrumental fluorescence lines ( al k@xmath1 at 1.49 kev and si k@xmath1 at 1.77 kev ) . in addition , the image above 1.8 kev shows no appreciable emission , so we ignore the energy band above 1.8 kev . the three x - ray images are displayed along with an h@xmath1 image of n70 in figure [ figure1 ] . the contours of h@xmath1 emission are overplotted on the x - ray images for comparison of their relative distributions . in the 0.40.7 and 0.71.0 kev bands , it can clearly be seen that elevated diffuse x - ray emission exists within the h@xmath1 shell . in the 1.01.3 kev band , there is an apparent strip of diffuse emission within n70 , but there are also patches of emission exterior to n70 . it is not clear whether the 1.01.3 kev emission projected within n70 is exclusively associated with n70 ; thus , we will focus on the 0.40.7 and 0.71.0 kev images for spatial analysis . these two soft energy bands are called s1 and s2 in this paper . the diffuse x - ray emission in the s1 and s2 bands , at a level of 70@xmath22 over the background , is well confined within the h@xmath1 shell of n70 . the bright diffuse x - ray emission is associated with the bright parts of the h@xmath1 shell , and the faint diffuse x - ray emission extends toward the faint h@xmath1 arcs to the east . the s1 band image shows three additional patches of diffuse x - ray emission on the east exterior to the h@xmath1 contours , but a closer examination of the h@xmath1 image shows that these diffuse x - ray patches are still enclosed within h@xmath1 filaments that are fainter than the lowest contour plotted . the diffuse x - ray surface brightness is not uniform within n70 . the background emission in the areas surrounding n70 shows variations , too . to investigate whether the variations in x - ray surface brightness are caused by uneven foreground absorption , we compare the column density map with the x - ray image in the 0.41.0 kev band in the left panel of figure [ figure6 ] . it is striking that an east west elongated cloud is coincident with the region of x - ray minimum , indicating that foreground absorption may indeed play a significant role in the nonuniform surface brightness of the diffuse x - rays in n70 . we have examined the channel maps and find that is detected at the position of n70 over @xmath19 = 295305 kms@xmath4 . the ionized gas in n70 shows similar velocities ( see figure 4 ) ; therefore , n70 may well be associated with the same complex . the lack of organized expansion structure in the around n70 is probably caused by n70 s being density - bounded with its surrounding gas completely ionized @xcite . indeed , our deep h@xmath1 image of n70 shows diffuse h@xmath1 emission exterior to the shell structure , indicating an extended ionized gas region . the velocity field may be further complicated by its location on the western rim of the supergiant shell 23 @xcite . to compare the distribution of diffuse x - ray emission with that of massive stars in n70 , the right panel of figure [ figure6 ] shows a color composite of n70 , with [ ] in green , [ ] in red , and 0.41.0 kev x - ray in blue . the six known o stars in n70 are marked . it can be seen that the [ ] image exhibits patchy emission near the massive stars and a filamentary shell structure centered on an o3if star ( r.a.=@xmath23 , decl.=67@xmath2451@xmath1416@xmath15 ) , currently the most massive star in lh114 . the centering of enhanced [ ] emission on massive stars indicates photoionization by stellar uv fluxes . the [ ] emission , on the other hand , shows the overall shell structure of n70 and encloses the diffuse x - ray emission , suggestive of a common origin for the [ ] emission and the x - ray - emitting hot plasma . lcc phabs ( @xmath25 ) ( @xmath26 ) & @xmath27 & @xmath28 + kt ( kev ) & @xmath29 & @xmath30 + norm ( @xmath31 ) & @xmath32 & @xmath33 + @xmath34dof & 0.96 ( 77.01/80 ) & 1.36 ( 31.24/23 ) + flux ( @xmath35erg @xmath36 s@xmath4)@xmath37 & @xmath38 & @xmath39 + @xmath40 @xmath41 ergs@xmath4 & @xmath42 & @xmath43 to assess the physical properties of the hot gas in n70 , we model the background - subtracted adaptively binned x - ray spectrum of the diffuse emission within n70 . figure [ figure7 ] shows the spectra individually extracted from the mos1 , mos2 , and pn . while the pn observation detected more counts , the mos spectra show better the line emission of at 0.57 kev , at 0.65 kev , and near 0.92 kev . the presence of the lines justifies the use of thermal plasma emission models . thus , we use the absorbed apec model and the xspec package ( version 12.7.1 ) to fit the x - ray spectrum of n70 for the energy range of 0.41.3 kev . the energy cutoff at 1.3 kev is selected because there is no appreciable emission above this energy . we fix the abundance at 1/3 solar , which is appropriate for the lmc @xcite . the mos1 , mos2 , and pn spectra are fit jointly , and the results are presented in table 1 . the absorption column density from the best fit is @xmath44 h - atom @xmath36 . this can be compared with that implied by the extinction toward the ob stars in n70 . most of the ob stars studied by @xcite have @xmath45 in the range of 0.10.2 mag , corresponding to @xmath46 of 0.320.64 mag . the milky way contribution to this extinction is @xmath47 mag @xcite , and the lmc contribution is @xmath48 0.1140.434 mag . using the gas to dust ratio of @xmath49 = @xmath50 h - atom @xmath36 mag@xmath4 for the milky way @xcite and @xmath51 h - atom @xmath36 mag@xmath4 for the lmc @xcite , the above extinction implies a h column density of 1.23.6@xmath1210@xmath52 h - atom @xmath36 toward most ob stars in n70 . this column density is in good agreement with the best - fit x - ray absorption column density , considering the non - uniform coverage of over n70 . the density of the hot gas in n70 can be derived from the normalization factor ( @xmath53 ) of the best - fit model of the x - ray spectra:@xmath54 where @xmath55 is the distance to n70 , @xmath56 and @xmath57 are electron and hydrogen number densities , @xmath58 is the filling factor , and @xmath59 is the volume of the n70 superbubble , all in cgs units . adopting an lmc distance of 50 kpc and a shell radius of 50 pc for n70 and assuming a he / h number ratio of 10% , the hydrogen atom density is @xmath57 = 0.1 @xmath60 @xmath61 . the total mass of the x - ray emitting gas is @xmath62 @xmath63 @xmath64 . such a large amount of mass suggests that the hot gas is mostly shock - heated interstellar matter . the _ xmm - newton _ observations of n185 were hampered by high background flares , and the useful exposure time was significantly shortened . because of its shorter exposure and lower surface brightness , diffuse x - ray emission from n185 is detected at a much lower s / n than that from n70 . the spatial and spectral analyses of n185 are quantitatively much more uncertain than those of n70 . the h@xmath1 image of n185 shows a complex structure . while its outer rim in the northern hemisphere and the southwest quadrant form a coherent shell morphology , its southeast quadrant appears to show a distinct , smaller shell morphology and additional blowout features extending outward to at least 2@xmath14 ( corresponding to 30 pc ) from the shell rim of n185 . mapping in the vicinity of n185 indicates a lack of associated gas @xcite . n185 thus seems to be located within the cavity of the supergiant shell lmc-7 @xcite . the x - ray images of n185 are produced with similar methods as we do for n70 . the useful observations of n185 were cut short by high background flares ; thus , the images of n185 have much lower s / n than those of n70 . the diffuse x - ray emission from n185 ( figure 2 ) is distributed mostly within the shell interior , but does extend to the southeast exterior . there is a particularly good correlation with the features in the southeast quadrant : the diffuse x - ray emission peaks within the interior shell and extends into the southeast blowout structure even beyond the h@xmath1 filaments . in the band of 0.40.7 kev , the diffuse emission in the blowout region rivals that at the peak within the shell . comparisons between the x - ray images of n185 and the column density map or channel maps do not show any enhancements in x - ray - faint regions within n185 . thus , the distribution of the diffuse x - ray emission reflects the distribution of the hot gas instead of the foreground absorption . the hot gas in n185 exists mostly in the small shell in the southeast quadrant and extends into the blowout region . comparisons between the x - ray and h@xmath1 images of n185 show anticorrelation between h@xmath1 and x - ray surface brightnesses in two regions . first , the bright east west oriented h@xmath1 filament that bisects n185 corresponds to a narrow strip of low surface brightness in the band of 0.71.0 kev ( in figure [ figure2](c ) ) . second , the area of low x - ray surface brightness between the blowout region and the shell interior emission region corresponds to the h@xmath1 shell rim ( in figure [ figure2](b ) ) . if these anticorrelations are caused by absorption of x - rays by the ionized gas shell of n185 , the blowout must be on the far side of the shell and the east west h@xmath1 filament must be caused by a density enhancement on the near side of the shell . the x - ray surface brightness of n185 is low . while figure [ figure2 ] shows apparent spatial variations in spectral properties of the diffuse x - ray emission in n185 , there are not enough counts to extract spectra separately from the shell interior and the blowout . we thus analyze the spectrum of the diffuse x - ray emission for the entire n185 , but determine the hardness ratios for the blowout and shell interior separately and compare them . because of the small number of counts , it is difficult to make satisfactory model fits to the x - ray spectra of n185 . after experimenting with different models , we find the hot gas in n185 to be best described by an absorbed apec model of optical thin hot gas in collisional ionization equilibrium without metal overabundance ( see also table 1 for the fitting results ) . to make crude estimates of the plasma properties , we have adopted the hydrogen column density derived from the @xmath45 = 0.14 of the o9 star in n185 @xcite as the absorption column density , @xmath65 h - atom @xmath36 . with this fixed absorption column , the best - fit model gives a gas temperature of @xmath66 kev and a normalization factor _ a _ of @xmath67 @xmath68 . assuming the hot gas originates from the interior of the shell structure with a 50 pc radius and a he / h number ratio of 10% , the hydrogen density is @xmath57 = 0.05 @xmath60 @xmath61 , and the hot gas mass is @xmath2 @xmath69 @xmath63 @xmath64 . the filling factor @xmath58 is most likely greater than 0.1 , and the hot gas mass is greater than 100 @xmath64 . this large mass is consistent with the hot gas being shock - heated interstellar gas without metal overabundance . although line features can not be discerned in figure 8 , a non - thermal ( _ powerlaw _ ) model yields an uncomfortably high photon index ( @xmath24.8 ) and large @xmath70 ( @xmath21.7 ) . the blowout region alone has too few counts for spectral analysis ( 17 , 29 , and 80 counts in mos1 , mos2 , and pn , respectively ) . it is only possible to compare the spectral hardness of the blowout with that of the shell interior . using the mos1+mos2+pn counts , we find the ( 0.71.0 kev)/(0.40.7 kev ) count ratio is [email protected] for the blowout and [email protected] for the shell interior . it thus appears that the blowout region has softer x - ray emission than the shell interior . softer x - ray emission is associated with cooler plasma temperature , which is expected for the hot gas expanding into regions with lower pressure . in a classical wind - blown bubble or a superbubble , shock - heated gas exists and emits in x - rays @xcite ; however , the x - ray emission from a superbubble is faint , unless off - center snrs impact the dense superbubble shell walls @xcite . both n70 and n185 encompass multiple ob stars , and thus their shells are naturally candidates of superbubbles . whether the shell is recently heated by an off - center sn can be determined by comparing the observed diffuse x - ray emission with that expected from a quiescent superbubble . the x - ray luminosity of a quiescent , i.e. , x - ray - dim , superbubble can be formulated as @xmath71 where @xmath72 is the superbubble expansion velocity in units of km s@xmath4 , @xmath73 is the superbubble radius in parsecs , @xmath74 is the hydrogen number density in the ambient interstellar medium in units of h - atom @xmath61 , @xmath75 is the metal abundance relative to the solar value , and @xmath76 is a dimensionless integral with a value of @xmath22 @xcite . the lmc metal abundance is roughly 1/3 solar , and thus @xmath77 1/3 . the densities of the ionized gas shells of n70 and n185 have both been estimated to be @xmath26.5 h - atom @xmath61 @xcite . assuming that the shell consists of swept - up ambient medium , then @xmath78 where @xmath79 is the shell radius , @xmath80 is the shell thickness , and @xmath81 is the shell density . both n70 and n185 have shell radii of @xmath250 pc and fractional shell thicknesses of [email protected] ; thus , the ambient density would be @xmath82 [email protected] h - atom @xmath61 . we adopt the shell expansion velocities determined from our echelle observations : @xmath83 km s@xmath4 for n70 and @xmath070 km s@xmath4 for n185 . using these shell parameters and ambient density , we expect the x - ray luminosity of a quiescent superbubble to be @xmath84 erg s@xmath4 for n70 and @xmath85 erg s@xmath4 for n185 . the luminosity of diffuse x - ray emission from n70 , determined from our observation and model fits to its spectrum , is @xmath86 erg s@xmath4 , higher than that expected from a quiescent superbubble , which can still be fainter if the expansion velocity of n70 is much lower than 35 km s@xmath4 . in contrast , the observationally determined diffuse x - ray luminosity of n185 ( @xmath87 erg s@xmath4 ) is an order of magnitude lower than that expected from a quiescent superbubble . n70 encompasses the ob association lh114 , and thus the uv flux and fast stellar winds from the massive stars are expected to photoionize the ambient medium and dynamically sweep the medium into a superbubble . its superbubble structure is complicated by the existence of a molecular cloud that is coincident with the bright patches of h@xmath1 emission and the ob association lh114 @xcite . the lack of pronounced absorption of the diffuse x - ray emission indicates that the dense molecular cloud is on the far side of the superbubble . massive young stellar objects have been found in n70 , and are associated with the molecular cloud @xcite . it appears that the star formation in n70 is still ongoing . we suggest that the ob association lh114 is formed in the molecular cloud but near its surface ; thus , n70 expands into the dense cloud on one side and forms a blister on the tenuous side , as shown by the illustrations in figure [ figure9 ] . the observed h@xmath1 morphology can be reproduced by observing with the line - of - sight nearly perpendicular to the cloud surface . given this configuration , the [ ] -bright shell structure corresponds to the dense hemisphere expanding into the dense cloud ; the blister side of the superbubble has a higher [ ] /h@xmath1 ratio with its west rim projected near the west rim of the [ ] shell rim and its east rim further east from the [ ] rim . the brightest optical emission from n70 corresponds to the photoionized dense hemisphere , whose free - free emission dominates in the radio wavelengths , resulting in a thermal spectral index . the x - ray luminosity from n70 , higher than that expected from a quiescent superbubble , suggests a recent occurrence of a sn that heats the hot gas in the superbubble interior . the age of the sn is not known , but must be younger than the age of the superbubble . a recent numerical three - dimensional hydrodynamic simulation of n70 has also concluded that the morphology , dynamics , and x - ray emission of n70 are best explained by a recent sn in a superbubble @xcite . n185 has a less dense environment than n70 . it is not associated with a molecular cloud or ongoing star formation , and it has no known ob association . if n185 is a superbubble , its x - ray luminosity is an order of magnitude lower than expected . while the x - ray emission from wind - blown bubbles has been observed to be lower than expected from bubble models ( e.g. , * ? ? ? * ; * ? ? ? * ; * ? ? ? * ; * ? ? ? * ) , it should be noted that the superbubble nature of n185 has not been rigorously established . the stellar population in n185 has been studied by @xcite . it is shown that the currently most massive stars in n185 include 10 early - b stars ( 1215 @xmath64 ) and 4 late - o stars ( 2025 @xmath64 ) , which are not powerful sources of fast stellar winds for superbubble formation . extrapolating the observed mass function to higher masses , it is expected that two stars in the mass range of 4060 @xmath64 have exploded as sne @xcite . the total mechanical energy injected by these two massive stars , both stellar winds and sn explosions , would by far exceed that from the combined wind energy provided by the lower - mass stars in n185 . the expansion velocity of n185 is high and irregular . the largest expansion velocity registered on the receding side of the shell reaches @xmath2200 km s@xmath4 . such a high expansion velocity is not seen in any superbubble in the lmc ; however , such fast expansion velocity and the irregular expansion are common characteristics of snrs in the lmc @xcite . furthermore , the radio emission from n185 is nonthermal , and the x - ray luminosity of n185 is consistent with that of an evolved snr in a low - density medium , such as snr 0450 - 70.9 @xcite . therefore , we suggest that a snr produced the diffuse x - ray emission , the smaller shell - like structure in the southeast quadrant , and the blowout structure of n185 . the large shell ( 100 pc in diameter ) is likely to be formed by an earlier event , possibly related to the first sn in n185 . the occurrence of two sne is consistent with the expectation from the observed stellar population in n185 , and they would indeed have played a dominant role in the formation of n185 s shell structure . n70 and n185 are two large [ ] -bright shells in the lmc . we have obtained _ xmm - newton _ x - ray observations and high - dispersion long - slit echelle spectroscopic observations of these two shells . these _ xmm - newton _ observations , much more sensitive than the previous _ einstein _ or _ rosat _ observations , allow useful spatial and spectral analyses for the first time . diffuse x - ray emission is detected from both shells and their apparent blowout regions , and the x - ray spectra are soft with plasma temperatures of @xmath88 kev . the x - ray luminosity of n70 is higher than that expected from a quiescent superbubble model ; thus , the interior of n70 is most likely heated by a recent sn . the x - ray luminosity of n185 is an order of magnitude lower than that expected from a quiescent superbubble with the size and expansion velocity of n185 . the hot gas in n185 is most likely originating from a snr , as it shows nonthermal radio emission , fast and irregular expansion , and its x - ray luminosity is consistent with that of an evolved snr . the large shell of n185 may be associated with an earlier sn event . these explanations are supported by the observed stellar population in these two large shell nebulae . this work has partially benefited from the support from nsfc grants 11233001 and 11203013 , the 973 program grant 2009cb824800 , srfdp of china 20120091110048 and 20110091120001 by the educational ministry of china , and grants by the 985 project of nju and the advanced discipline construction project of jiangsu province . r.m.w . and y.h.c . acknowledge the support of nasa grant nnx06ah65 g . we also thank wei sun and ping zhou for helpful discussions .
n70 and n185 are two large ( @xmath0100 pc in diameter ) shell nebulae in the large magellanic cloud ( lmc ) . their high [ ] /h@xmath1 ratios rival those of supernova remnants ( snrs ) , but they are not confirmed as snrs . to study their physical nature , we have obtained _ xmm - newton _ x - ray observations and high - dispersion long - slit echelle spectroscopic observations of these two nebulae . the x - ray spectra of both nebulae can be well interpreted with an optically thin thermal ( @xmath20.2 kev ) plasma with the average lmc abundance in a collisional ionization equilibrium . n70 encompasses the ob association lh114 . although n70 has a modest expansion velocity and essentially thermal radio emission , its diffuse x - ray luminosity ( @xmath3 erg s@xmath4 ) is higher than that from a quiescent superbubble with n70 s density , size , and expansion velocity ; thus , n70 is most likely a superbubble that is recently energized by an interior snr . n185 does not contain any known ob association , and its x - ray luminosity is an order of magnitude lower than expected if it is a quiescent superbubble . n185 has nonthermal radio emission and has high - velocity material expanding at nearly 200 km s@xmath4 , similar to many known snrs in the lmc . its x - ray luminosity ( @xmath5 erg s@xmath4 ) is also consistent with that of an evolved snr . we therefore suggest that n185 is energized by a recent supernova .
A mystery carving believed to date back to the 13th century has been discovered on the walls of a castle on Mull. While investigations into the carving at Duart Castle continue, some experts say it may be a quasi-erotic image known as a Sheela Na Gig. Often found on old churches, to protect the building from evil spirits, Sheela Na Gigs traditionally depict a naked woman with an ugly face. However, the Duart carving is so weather-worn it is difficult to determine its origin. Sir Lachlan Maclean, 73, the clan chief who owns the Maclean stronghold of Duart Castle, had no knowledge of the carving until a guide noticed it. He said: “I had never noticed it before but once it’s been pointed out to you it’s quite clear – although you do have to be looking at the right angle.” Nic Broomhead, who made the discovery, said: “The light happened to hit the wall at the right angle to show the carving up. “It is a depiction of a woman and it’s a rather unusual one. The mystery is where has it come from, because it is not carved in local stone, it is different from all the other stonework on the castle. We don’t know if it was brought here from elsewhere.” The castle was a ruin until 1912 but there are photos of the building in 1905, before it was restored, and the carving is there then. He added: “We are not sure what it is but in the past two or three weeks we have been trying to circulate pictures of it to academics. “We have talked to a number of people, including experts at Dublin University and an archaeologist in Nottinghamshire and the general impression is that it is from around the 13th century.” Some experts think it’s a hagstone – a stone with a natural hole running through it which is said to hold magical powers of protection. Andrew Bradley, a stonemason who is carrying our restoration work at the castle, said: “It is heavily weathered and it needs more research into it, but it’s obviously meant something to somebody, there is obviously a reason for it being carved and a reason for it being at Duart. “It’s the only piece of carved stonework on the castle, other than the armorial coat of arms that were done in the 1910-1912 restoration.” ||||| Every Historic Environment Scotland (HES) grant made since 1 April 2018 is listed below. A list of grants made in previous years can be accessed at the bottom of this page. Grants awarded 2018-19 Recipient Project Scheme Grant Date Built Environment Forum Scotland Scottish Traditional Building Forum HESF £30,000 18/07/2018 Shona Johnson Presenting at 4 day Festival of Ironwork HESF £1,865 18/07/2018 The Scottish Traditional Skills Training Centre Traditional Skills training courses HESF (2018-2021) £94,500 17/07/2018 St Conan's Church Trust St Conan's Kirk, Lochawe Grants for Places of Worship £50,000 17/07/2018 Scottish Lime Centre Trust Delivery of training and education programme HESF £22,000 13/07/2018 Galgael Trust Delivery of training courses and heritage visits HESF £37,329 13/07/2018 Galston Parish Church Galston Parish Church, Galston Grants for Places of Worship £122,300 13/07/2018 The Society for the Protection of Ancient Buildings The William Morris Craft Fellowship HESF £5,500 13/07/2018 Bridgefield Services Ltd SQA Qualifications HESF £1,000 13/07/2018 Edinburgh and Lothians Greenspace Trust Mavisbank House - Community Engagement Officer HESF £9,841 05/07/2018 University of Aberdeen Production of an animation film on Dunnicaer Promonory Fort HESF £4,593 05/07/2018 Cambo Heritage Trust Condition Survey - Walled Garden and other structures HESF £2,500 05/07/2018 Earl Haig Fund Scotland Production of a free publications for schools HESF £6,746 05/07/2018 Archdiocese of Glasgow Holy Family and St Ninian's Church, Glasgow Grants for Places of Worship £137,000 28/06/2018 Built Environment Forum Scotland Strategic Intermediary Body for Historic Environment (2018-21) Organisational Support Fund £429,335 20/06/2018 St Meddan's Church of Scotland St Meddan's Church of Scotland Grants for Places of Worship £118,200 11/06/2018 Gardner Memorial Church of Scotland Gardner Memorial Church of Scotland Grants for Places of Worship £109,800 11/06/2018 Prestongrange Parish Church Prestongrange Parish Church, Prestonpans Grants for Places of Worship £37,300 11/06/2018 Archaeology Strategy Aim 4 (3yr offer 2018-21) Archaeology Strategy Aim 4 (3yr offer 2018-21) Archaeolgoy £153,620 04/05/2018 Adopt-a-Monument (2018-19) Adopt-a-Monument (2018-19) Archaeology £50,000 04/05/2018 Stobs Camp (2018-19) Stobs Camp (2018-19) Archaeology £15,000 04/05/2018 Dig It (2018-19) Dig It (2018-19) Archaeology £80,000 04/05/2018 Highland Archaeology Framework (3yr offer 2018-21) Highland Archaeology Framework (3yr offer 2018-21) Archaeology £96,630 04/05/2018 Islands Archaeology Research Framework (3yr offer 2018-21) Islands Archaeology Research Framework (3yr offer 2018-21) Archaeology £125,340 04/05/2018 Perth & Kinross Archaeology (3yr offer 2018-21) Perth & Kinross Archaeology (3yr offer 2018-21) Archaeology £107,469 04/05/2018 National Trust for Scotland Annual Maintenance Plan Organisational Support Fund £1,320,000 04/05/2018 Scottish Civic Trust Resilience Project Organisational Support Fund £10,051 27/04/2018 New Lanark Trust Organisation Support 2018-2019 Organisational Support Fund £180,000 27/04/2018 Scottish Civic Trust Organisation Support Fund 2018-2021 Organisational Support Fund £239,743 27/04/2018 The Auchindrain Trust Organisation Support 2018-2019 Organisational Support Fund £185,000 16/04/2018 St Brides Parish Church of Scotland St Brides Parish Church of Scotland, Sanquhar Grants for Places of Worship £108,800 13/04/2018 Dunvegan Church of Scotland Dunvegan Church of Scotland, Isle of Skye Grants for Places of Worship £50,000 09/04/2018 Portsoy Hall Church Portsoy Hall Church, Portsoy Grants for Places of Worship £32,500 09/04/2018 War Memorials Trust Organisation Support 2018-2019 Organisational Support Fund £16,500 04/04/2018 The Ridge Foundation Stonemason Training Project HESF £46,532 04/04/2018 Mavisbank Trust Digital reconstruction of Mavisbank House HESF £5,000 04/04/2018 CARS - Conservation Area Regeneration Scheme HESF - Historic Environment Support Fund Find out more about grants and funding. Previous years grants Grants Awarded 2017-18 [PDF, 132KB] Grants Awarded 2016-17 [PDF, 141KB] Grants Awarded 2015-16 [PDF, 118KB] Contact Investment Team Historic Environment Scotland Longmore House Salisbury Place Edinburgh EH9 1SH Telephone: 0131 668 8801 Email: [email protected] ||||| Help to Save Duart Castle An appeal from the Chief of the Clan Maclean Introduction At the Clan Congress on Mull in June 2012 I told the Macleans present that my family could no longer afford the repairs that we had undertaken at the Castle in the previous 100 years. I asked them if they would help with the repairs that we needed to do to make the Castle watertight. The unanimous response of those present was that they wanted to help. I am therefore launching this appeal to both Macleans and members of the public who are interested in saving Duart for future generations. Castle history The Keep at Duart was built in 1360 when Lachlan Lubanach, the 5th Chief, married Mary Macdonald, the daughter of the Lord of the Isles. She brought Duart as her dowry. Lachlan built the Keep and the north-west part of the site. The other two wings were added in the 16th and 17th centuries. My family lost the Castle in the late 17th century when the Earl of Argyll took the Castle and our lands to pay off the family’s debts. In 1911 my great-grandfather, Sir Fitzroy Maclean, the 26th Chief, bought back the Castle and in the period up to the First World War restored it to the building you see today.
– Tom Hanks' next role: Sir Lachlan Hector Charles Maclean? The Scottish lord has for the last 26 years been dealing with the king of all money pits. Repairs on the 14th-century Duart Castle he inherited have thus far cost just shy of $2 million, reports the New York Times, which spoke to Sir Lachlan in his living room—"probably one of the snugger parts of the castle ... though it was still mildly damp." That dampness is the issue. The castle "leaks like a sieve," per a Times of London article from July on a $420,000 grant awarded for wall repairs. Those walls are 16-feet thick, and yet apparently still unable to keep out the incessant rain: Located on the Isle of Mull off Scotland's west coast, rain falls, on average, all but 82 days of the year. The entry fees paid by some 25,000 visitors a year (note of warning for guests, per the New York Times: the two ancient toilets don't function) help fund the repairs, but Sir Lachlan tells the paper he expects there won't be money to keep them going after 2017. This after Sir Lachlan in June 2012 informed the Maclean Clan Congress that his family couldn't afford further repairs; a public appeal was launched at the time, only to be followed in the winter of 2013 with the collapse of four ceilings due to water penetration. And "I don’t think Scotland can afford to lose a building like this," the Times of London quotes him as saying. It's one of the only clan castles in private hands, and replete with tales of clashes with the rival Campbell clan, Spanish prisoners kept in its dungeon, and, as the Scotsman reported, a mysterious carving on its wall.
SECTION 1. SHORT TITLE. This Act may be cited as the ``Tropical Forest and Coral Conservation Reauthorization Act of 2009''. SEC. 2. AMENDMENT TO SHORT TITLE OF ACT TO ENCOMPASS EXPANDED SCOPE. (a) In General.--Section 801 of the Tropical Forest Conservation Act of 1998 (Public Law 87-195; 22 U.S.C. 2151 note) is amended by striking ``Tropical Forest Conservation Act of 1998'' and inserting ``Tropical Forest and Coral Conservation Act of 2009''. (b) References.--Any reference in any other provision of law, regulation, document, paper, or other record of the United States to the ``Tropical Forest Conservation Act of 1998'' shall be deemed to be a reference to the ``Tropical Forest and Coral Conservation Act of 2009''. SEC. 3. EXPANSION OF SCOPE OF ACT TO PROTECT FORESTS AND CORAL REEFS. (a) In General.--Section 802 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431), as renamed by section 2(a), is amended-- (1) in subsections (a)(1), (a)(6), (a)(7), (b)(1), (b)(3), and (b)(4), by striking ``tropical forests'' each place it appears and inserting ``tropical forests and coral reefs and associated coastal marine ecosystems''; (2) in subsection (a)(2)-- (A) in subparagraph (A), by striking ``resources, which are the basis for developing pharmaceutical products and revitalizing agricultural crops'' and inserting ``resources''; and (B) in subparagraph (C), by striking ``far-flung''; and (3) in subsection (b)(2)-- (A) by striking ``tropical forests'' the first place it appears and inserting ``tropical forests and coral reefs and associated coastal marine ecosystems''; (B) by striking ``tropical forests'' the second place it appears and inserting ``areas''; (C) by striking ``tropical forests'' the third place it appears and inserting ``tropical forests and coral reefs and their associated coastal marine ecosystems''; and (D) by striking ``that have led to deforestation'' and inserting ``on such countries''. (b) Amendments Related to Definitions.--Section 803 of such Act (22 U.S.C. 2431a) is amended-- (1) in paragraph (5)-- (A) in the heading, by striking ``tropical forest'' and inserting ``tropical forest or coral reef''; (B) in the matter preceding subparagraph (A), by striking ``tropical forest'' and inserting ``tropical forest or coral reef''; and (C) in subparagraph (B)-- (i) by striking ``tropical forest'' and inserting ``tropical forest or coral reef''; and (ii) by striking ``tropical forests'' and inserting ``tropical forests or coral reefs'' (2) by adding at the end the following new paragraphs: ``(10) Coral.--The term `coral' means species of the phylum Cnidaria, including-- ``(A) all species of the orders Antipatharia (black corals), Scleractinia (stony corals), Alcyonacea (soft corals), Gorgonacea (horny corals), Stolonifera (organpipe corals and others), and Coenothecalia (blue coral), of the class Anthoza; and ``(B) all species of the order Hydrocorallina (fire corals and hydrocorals) of the class Hydrozoa. ``(11) Coral reef.--The term `coral reef' means any reef or shoal composed primarily of coral. ``(12) Associated coastal marine ecosystem.--The term `associated coastal marine ecosystem' means any coastal marine ecosystem surrounding, or directly related to, a coral reef and important to maintaining the ecological integrity of that coral reef, such as seagrasses, mangroves, sandy seabed communities, and immediately adjacent coastal areas.''. SEC. 4. CHANGE TO NAME OF FACILITY. (a) In General.--Section 804 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431b), as renamed by section 2(a), is amended by striking ``Tropical Forest Facility'' and inserting ``Conservation Facility''. (b) Conforming Amendments to Definitions.--Section 803(8) of such Act (22 U.S.C. 2431a(8)) is amended-- (1) in the heading, by striking ``Tropical forest facility'' and inserting ``Conservation facility''; and (2) by striking ``Tropical Forest Facility'' both places it appears and inserting ``Conservation Facility''. (c) References.--Any reference in any other provision of law, regulation, document, paper, or other record of the United States to the ``Tropical Forest Facility'' shall be deemed to be a reference to the ``Conservation Facility''. SEC. 5. ELIGIBILITY FOR BENEFITS. Section 805(a) of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431c(a)), as renamed by section 2(a), is amended by striking ``tropical forest'' and inserting ``tropical forest or coral reef''. SEC. 6. UNITED STATES GOVERNMENT REPRESENTATION ON OVERSIGHT BODIES FOR GRANTS FROM DEBT-FOR-NATURE SWAPS AND DEBT BUYBACKS. Section 808(a)(5) of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431f(a)(5)), as renamed by section 2(a), is amended by adding at the end the following new subparagraph: ``(C) United states government representation on the administering body.--One or more individuals appointed by the United States Government may serve in an official capacity on the administering body that oversees the implementation of grants arising from a debt-for-nature swap or debt buyback regardless of whether the United States is a party to any agreement between the eligible purchaser and the government of the beneficiary country.''. SEC. 7. CONSERVATION AGREEMENTS. (a) Renaming of Agreements.--Section 809 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431g), as renamed by section 2(a), is amended-- (1) in the section heading, by striking ``tropical forest agreement'' and inserting ``conservation agreement''; and (2) in subsection (a)-- (A) by striking ``Authority'' and all that follows through ``(1) In general.--The Secretary'' and inserting ``Authority.--The Secretary''; and (B) by striking ``Tropical Forest Agreement'' and inserting ``Conservation Agreement''. (b) Elimination of Requirement To Consult With the Enterprise for the Americas Board.--Such subsection is further amended by striking paragraph (2). (c) Role of Beneficiary Countries.--Such section is further amended-- (1) in subsection (e)(1)(C), by striking ``in exceptional circumstances, the government of the beneficiary country'' and inserting ``in limited circumstances, the government of the beneficiary country when needed to improve governance and enhance management of tropical forests or coral reefs or associated coastal marine ecosystems, without replacing existing levels of financial efforts by the government of the beneficiary country and with priority given to projects that complement grants made under subparagraphs (A) and (B)''; and (2) by amending subsection (f) to read as follows: ``(f) Review of Larger Grants.--Any grant of more than $250,000 from a Fund must be approved by the Government of the United States and the government of the beneficiary country.''. (d) Technical and Conforming Amendments.--Such section is further amended-- (1) in subsection (c)(2)(A)(i), by inserting ``to serve in an official capacity'' after ``Government''; (2) in subsection (d)-- (A) in the matter preceding paragraph (1), by striking ``tropical forests'' and inserting ``tropical forests and coral reefs and associated coastal marine ecosystems related to such coral reefs''; (B) in paragraph (5), by striking ``tropical forest''; and (C) in paragraph (6), by striking ``living in or near a tropical forest in a manner consistent with protecting such tropical forest'' and inserting ``dependent on a tropical forest or coral reef or an associated coastal marine ecosystem related to such coral reef and related resources in a manner consistent with conserving such resources''. (e) Conforming Amendments to Definitions.--Section 803(7) of such Act (22 U.S.C. 2431a(7)) is amended-- (1) in the heading, by striking ``Tropical forest agreement'' and inserting ``Conservation agreement''; and (2) by striking ``Tropical Forest Agreement'' both places it appears and inserting ``Conservation Agreement''. SEC. 8. CONSERVATION FUND. (a) In General.--Section 810 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431h), as renamed by section 2(a), is amended-- (1) in the section heading, by striking ``tropical forest fund'' and inserting ``conservation fund''; and (2) in subsection (a)-- (A) by striking ``Tropical Forest Agreement'' and inserting ``Conservation Agreement''; and (B) by striking ``Tropical Forest Fund'' and inserting ``Conservation Fund''. (b) Conforming Amendments to Definitions.--Such Act is further amended-- (1) in section 803(9) (22 U.S.C. 2431a(9))-- (A) in the heading, by striking ``Tropical forest fund'' and inserting ``Conservation fund''; and (B) by striking ``Tropical Forest Fund'' both places it appears and inserting ``Conservation Fund''; (2) in section 806(c)(2) (22 U.S.C. 2431d(c)(2)), by striking ``Tropical Forest Fund'' and inserting ``Conservation Fund''; and (3) in section 807(c)(2) (22 U.S.C. 2431e(c)(2)), by striking ``Tropical Forest Fund'' and inserting ``Conservation Fund''. SEC. 9. REPEAL OF AUTHORITY OF THE ENTERPRISE FOR THE AMERICAS BOARD TO CARRY OUT ACTIVITIES UNDER THE TROPICAL FOREST AND CORAL CONSERVATION ACT OF 2009. (a) In General.--Section 811 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431i), as renamed by section 2(a), is repealed. (b) Conforming Amendments.--Section 803 of such Act (22 U.S.C. 2431a), as renamed by section 2(a), is amended-- (1) by striking paragraph (4); and (2) by redesignating paragraphs (5), (6), (7), (8), and (9) as paragraphs (4), (5), (6), (7), and (8), respectively. SEC. 10. CHANGES TO DUE DATES OF ANNUAL REPORTS TO CONGRESS. Section 813 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431k), as renamed by section 2(a), is amended-- (1) in subsection (a)-- (A) by striking ``(a) In General.--Not later than December 31'' and inserting ``Not later than April 15''; (B) by striking ``Facility'' both places it appears and inserting ``Conservation Facility''; and (C) by striking ``fiscal year'' both places it appears and inserting ``calendar year''; and (2) by striking subsection (b). SEC. 11. CHANGES TO INTERNATIONAL MONETARY FUND CRITERION FOR COUNTRY ELIGIBILITY. Section 703(a)(5) of the Foreign Assistance Act of 1961 (22 U.S.C. 2430b(a)(5)) is amended-- (1) by striking ``or, as appropriate in exceptional circumstances,'' and inserting ``or''; (2) in subparagraph (A)-- (A) by striking ``or in exceptional circumstances, a Fund monitored program or its equivalent,'' and inserting ``or a Fund monitored program, or is implementing sound macroeconomic policies,''; and (B) by striking ``(after consultation with the Enterprise for the Americas Board)''; and (3) in subparagraph (B), by striking ``(after consultation with the Enterprise for Americas Board)''. SEC. 12. NEW AUTHORIZATION OF APPROPRIATIONS FOR THE REDUCTION OF DEBT AND AUTHORIZATION FOR AUDIT, EVALUATION, MONITORING, AND ADMINISTRATION EXPENSES. Section 806 of the Tropical Forest and Coral Conservation Act of 2009 (22 U.S.C. 2431d), as renamed by section 2(a), is amended-- (1) in subsection (d), by adding at the end the following new paragraphs: ``(7) $25,000,000 for fiscal year 2009. ``(8) $30,000,000 for fiscal year 2010. ``(9) $30,000,000 for fiscal year 2011. ``(10) $30,000,000 for fiscal year 2012.''; and (2) by amending subsection (e) to read as follows: ``(e) Use of Funds To Conduct Program Audits, Evaluations, Monitoring, and Administration.--Of the amounts made available to carry out this part for a fiscal year, $300,000 is authorized to be made available to carry out audits, evaluations, monitoring, and administration of programs under this part, including personnel costs associated with such audits, evaluations, monitoring and administration.''.
Tropical Forest and Coral Conservation Reauthorization Act of 2009 - (Sec. 2) Renames the Tropical Forest Conservation Act of 1998 as The Tropical Forest and Coral Conservation Act of 2009. (Sec. 3) Includes tropical forests and coral reefs and associated coastal marine ecosystems within the scope of such Act. Defines "coral" as species of the phylum Cnidaria, including: (1) all species of the orders Antipatharia (black corals), Scleractinia (stony corals), Alcyonacea (soft corals), Gorgonacea (horny corals), Stolonifera (organpipe corals and others), and Coenothecalia (blue coral), of the class Anthoza; and (2) all species of the order Hydrocorallina (fire corals and hydrocorals) of the class Hydrozoa. Defines "associated coastal marine ecosystem" as any coastal marine ecosystem surrounding, or directly related to, a coral reef and important to maintaining the ecological integrity of that coral reef, such as seagrasses, mangroves, sandy seabed communities, and immediately adjacent coastal areas. (Sec. 4) Renames the Tropical Forest Facility as the Conservation Facility. (Sec. 6) Authorizes U.S. government representation on the administering body that oversees the implementation of grants from a debt-for-nature swap or debt buy-back regardless of whether the United States is a party to any agreement between the eligible purchaser and the government of the beneficiary country. (Sec. 7) Requires U.S. government and beneficiary country government review of Conservation Fund grants in excess of $250,000. (Sec. 9) Repeals Enterprise of the Americas Board authority to carry out activities under the Act. (Sec. 10) Changes the due date for the annual Facility report to Congress from December 31 to April 15. (Sec. 11) Revises country eligibility criteria. (Sec. 12) Authorizes FY2009-FY2012 appropriations for debt reduction. Increases annual funds available for program audits and evaluation, and makes such funds available for program monitoring and administration.
according to landauer s principle @xcite any logically irreversible operation on information , is always associated with a loss of energy . for example , each bit of lost information leads to the release of at least ktln2 amount of heat . this type of energy loss is expected to become a substantial part of energy dissipation in vlsi circuits in near future . the energy dissipation problem of vlsi circuits can be circumvented by using reversible logic because reversible computation does not require to erase any bit of information . this observation has motivated scientists to design reversible circuits for various purposes @xcite-@xcite . if the reversible circuit implements quantum computation and it comprises of quantum gates then it is a quantum circuit and if the reversible circuit implements only classical computation ( boolean logic ) then it is a classical reversible circuit . in the area of quantum computing several new possibilities appeared which are impossible in classical domain . to be precise , quantum teleportation @xcite , infinitesimally secured cryptography @xcite and super dense - coding @xcite do not have any classical analogue . all these unique features of quantum communication are associated with some circuits which are reversible in nature . in other words , we require quantum circuits to implement quantum algorithms and protocols . for example , circuits are proposed for implementation of shor s algorithm @xcite , quantum teleportation @xcite , various attacks on quantum key distribution protocols @xcite , super dense coding @xcite , quantum error correction @xcite , fault tolerant quantum computation @xcite-@xcite , grover s algorithm @xcite-@xcite , nondestructive discrimination of bell states @xcite , quantum circuits for addition @xcite etc . here we would like to note that all quantum mechanical operations are reversible and the only difference between a classical reversible gate and a quantum gate is that the classical reversible gate can not handle superposition of states ( qubit ) . consequently , set of all classical reversible gates form a subset of set of all quantum gates . for example , cnot gate can be achieved in classical and quantum domains but the hadamard gate can be achieved in quantum domain only . therefore , classical reversible circuits are only a subset of quantum circuits and any protocol designed for optimization of particular parameter related to quantum circuits will also be valid for classical reversible circuits . we have tried to explain the requirement and beauty of quantum circuits and now the question arises : how to obtain these circuits ? there exist several algorithms for synthesis of classical reversible circuits @xcite and quantum circuits @xcite-@xcite . but these algorithms do not provide a unique output . for example , a reversible multiplier can be achieved in many ways @xcite-@xcite . therefore , a quantitative measure of the quality of a circuit is required . some of the important quantitative measures are gate count , number of garbage bits and quantum cost . gate count is the total number of gates in a circuit , but there is a specific problem with this quantitative measure of circuit quality . specially it is not unique . if one is allowed to introduce a new gate or a complex gate library then the gate count can be considerably reduced . an n - qubit reversible gate is represented by @xmath0 unitary matrix . product of any arbitrary number of unitary matrices is always unitary . moreover serial connection of such gates correspond to multiplication of their matrices and parallel connection corresponds to tensor multiplication of their matrices . therefore , if we put a set of reversible quantum gate in a black box then it can be visualized as a new gate . thus the gate count can be reduced to 1 . for example in @xcite the circuit cost of a full adder circuit from nct gate library is 4 , in @xcite it is reduced to 2 by using peres gate and in @xcite it is reduced to 1 by using a new gate . all the differences in circuit cost of full adder is because of choice of non unique gate libraries . consequently it is important to define an unique gate library for comparison of circuit cost . further , a good quantum circuit requires minimum number of garbage bits . this is so because garbage bit is defined as an additional output bit which is required to make a function reversible and it is not used for further computations . the quantum cost @xcite of a reversible circuit is the number of primitive quantum gates needed to implement a circuit . primitive quantum gates are the elementary building blocks @xcite-@xcite , like not gate , cnot gate , controlled-@xmath1 , controlled-@xmath2 , rotation gates etc . we can construct toffoli gate with square root of not gate ( v ) and cnot gate and in that construction the minimum gate count of toffoli gate is 5 @xcite and its quantum cost is also 5 . these requirements yield separate measures of quality of a quantum circuit . to be precise , the circuit is better if it has lesser number of garbage bits , circuit cost and quantum cost . but it is often observed that reduction of circuit cost leads to increase in garbage bits and reduction of quantum cost leads to increase in circuit cost @xcite . keeping these in mind we have recently introduced a new parameter called total cost ( tc ) @xcite which is the sum of gate count of an optimized circuit , number of garbage bits and quantum cost . for reduction of tc it is required to simultaneously reduce the circuit cost , garbage count and quantum cost . this is an open problem and at present neither an algorithm for simultaneous reduction of all these measures nor a satisfactory algorithm for reduction of quantum cost exist . before we address the more complex problem of minimization of tc we have to device a protocol for reduction of quantum cost . in some works @xcite the quantum cost is calculated straight by adding the quantum cost of respective reversible gates in the circuit or it is optimized by applying deletion rule only . a simple minded systematic approach is also proposed by maslov _ these facts have motivated us to design an algorithm for minimization of quantum cost and to apply our algorithm to compute quantum cost of different circuits in @xcite . in the next section we have discussed the earlier approaches and their limitations . in section 3 , we have proposed an algorithm for calculating the quantum cost of reversible circuits . here we have also compared our results with the earlier proposals @xcite to establish that the quantum cost computed by the proposed algorithm is minimum . finally we conclude in section 4 . cost of an arbitrary unitary gate was first introduced by barenco _ et al . _ in 1995 @xcite . they had considered all @xmath3 gate and cnot gate as basic gates and had shown that for any @xmath3 unitary gate u unitary matrix . therefore a @xmath3 and @xmath4 gates correspond to 1 qubit and 2 qubit gates respectively . different notations have been used in @xcite . ] , we can realize c - u ( corresponding controlled u gate ) by using at most 6 basic gates . but to analyze the cost of a large gate ( n bit toffoli ) he had considered the cost of c - u as @xmath5 . next year , smolin and divincenzo @xcite calculated cost of fredkin gate . in their calculation they went beyond the definition of barenco _ et al . _ and assumed that the cost of every @xmath4 gate is 1 . this consideration does not have any contradiction with barenco _ et al_. s definition of cost , as cost of all 2 qubit quantum gates is @xmath5 . further progress in cost calculation was made by perkowski _ @xcite in 2003 where they show that a one qubit gate costs nothing , if it precedes or follows by a 2 qubit gate . this is so because one qubit gate can be combined with the 2 qubit gate to yield a new two qubit gate . thus , the cost is calculated as a total sum of @xmath4 gates used . following this definition the cost of swap gate is one and that of peres gate is four . peres gate is universal for reversible boolean operations and it has the minimum cost compared to other universal gates . this observation of perkowski _ et al . _ had motivated others to use peres gate to minimize the cost . for example , maslov and duek @xcite have used the idea of perkowski _ et al . _ and have shown that , the number of elementary quantum operations required to implement peres gate is less so it can be substituted for n - bit toffoli network to reduce the cost of n - bit toffoli gates . here we would like to note that in the earlier works @xcite quantum cost was mentioned as cost . the term quantum cost was coined by maslov _ et al_. @xcite in 2003 , they have defined quantum cost of a gate g , as the number of elementary quantum operations required to realize the function given by g. later on , hung _ @xcite had reconsidered the quantum cost estimation protocol defined by smolin and divincenzo @xcite . they have stated that each two qubit gate and each symmetric gate pattern ( see fig . 2 of @xcite ) have quantum implementation cost 1 . in essence all these definitions of quantum cost are synonymous and we can follow perkowski s definition @xcite and state that the quantum cost of a classical reversible or quantum circuit is the minimum number of one qubit and two qubit quantum gates needed to implement the circuit . in recent past quantum cost of different classical reversible and quantum circuits have been reported @xcite . simultaneously several efforts have been made to reduce the quantum cost of different gates / circuits . for example , barenco _ et al . _ @xcite estimated the cost of a 6 bit toffoli gate as 61 . maslov and duek @xcite reduced the quantum cost of this gate initially to 48 by using peres gate . further maslov _ et al . _ @xcite reduced the quantum cost of this gate to 38 by applying local optimization tools . there also exist following two online databases : i ) benchmark page of maslov _ et al . _ @xcite and ii ) revlib @xcite , which include quantum cost of different circuits calculated by different authors . in 2005 _ @xcite have shown that a closer look into the cost metric can classify them into two subclasses : linear cost ( where the quantum cost of a circuit is calculated as sum of quantum cost of each gate ) and nonlinear cost ( where local optimization algorithm is used ) . according to this classification scheme @xcite quantum cost defined in smolin and divincenzo @xcite and hung _ et al_. @xcite is nonlinear . interestingly , haghparast and eshghi @xcite have given following two prescriptions for calculation of quantum cost : 1 . implement a circuit / gate using only the quantum primitive @xmath6 and @xmath7 gates and count them 2 . synthesize the new circuit / gate using the well known gates whose quantum cost is specified and add up their quantum cost to calculate total quantum cost . in both of these cases we will obtain linear cost metric and consequently the quantum cost obtained in these two procedures may be higher than the actual one unless local optimization algorithms are applied to the entire circuit . when we apply the local optimization algorithm on the entire circuit then we obtain a nonlinear cost metric . the proposed algorithm will calculate nonlinear cost metric . local optimization is expected to play an important role in minimization of quantum cost . _ @xcite have realized this fact and have proposed an algorithm for minimization of quantum cost by applying templates and it yields nonlinear cost metric . our current work and work of maslov _ et al . s @xcite is contemporaneous and independent . they differ greatly in their premises , methods and consequences . 1 ) maslov _ et al . _ s work deal with circuit optimization precisely minimizing gate count by local optimization tools . they have introduced templates and applied them to optimize the gate count . in contrast , our algorithm exploits a conceptual difference between optimization algorithm used for reduction of gate count and the one used for reduction of quantum cost . 2 ) they are restricted to a particular gate library but to reduce the quantum cost we have introduced new gates as long as the gate is @xmath3 or @xmath4 quantum gate . 3 ) in their work the local optimization tools reduces the gate count only , but in our work it is applied to reduce the quantum cost as well . this is shown in fig . 2c where moving rule @xcite ( which was essentially designed to reduce circuit complexity ) has not reduced the circuit complexity but has reduced the quantum cost . this is evident in the work of smolin @xcite . further , we would like to note that the quantum cost obtained by maslov _ et al . _ is not linear and so is ours . consequently it will be completely justified to compare the quantum cost obtained by our proposed algorithm with that obtained using maslov _ s algorithm . in this section we have proposed an algorithm that optimizes the quantum cost of classical reversible and quantum circuits . it is presented in the form of a flowchart in fig 1 . the flowchart is explained below : . c ) moving rule is applied ( the movements are shown by arrows ) , d ) and e ) template matching rule is applied . f ) new gates are introduced ( dashed boxes ) and the quantum cost is 11 . g ) the circuit shown in fig 2a is reduced here by template matching to one toffoli and two cnot gates . h ) the toffoli gate is substituted by quantum primitives . according to haghparast and eshghi s methods @xcite the quantum cost is now 7 . the moving rule is applied to circuit . i ) new gates are introduced to yield quantum cost of fredkin gate as 5 . ] the input is a reversible circuit . here we would like to note that our goal is to find out the minimum number of quantum primitive gates required to implement the circuit and we are not much concerned about the choice of gate library @xcite in principle . but in practice it is easier to work using an input circuit which is constituted using the gates from a standard gate library for which a large / complete set of templates are known . at present there are few set of templates , available for classical reversible circuits @xcite . however not much templates @xcite are reported for quantum circuits and it is not difficult to generate them . therefore , in the beginning of the algorithm we convert the input reversible circuit into a circuit composed of gates taken from a standard gate library preferably those gate libraries for which a complete / large set of templates are already known . 2 . in the next step we optimize the gate count of the reversible circuit by applying local optimization tools which are moving rule , deletion rule and template matching . we apply moving rule or commutation rule @xcite which is simply a matrix operation to see whether the adjacent gates commute or not . this operation is useful to reduce the gate count with the help of self inverse rule and template matching @xcite . if at any point of time we find that the adjacent gates are of the same type and they form an identity ( i ) then we can remove both of the identical gates . this is called self inverse or deletion rule . in nct gate library , all the gates are self inverse and in ncv gate library apart from the square root of not gate ( where @xmath1.@xmath2 = i ) all the remaining gates are self inverse . in template matching @xcite a sequence of gates is substituted by another sequence of gates having lesser number of gate count and same operational effect . suppose we have a template : @xmath8=i ( where @xmath9 is an unitary gate ) and in the optimization procedure we come across a sequence of gates @xmath10 then we can replace this sequence of gates by @xmath11 . + + 3 . in this step we obtain an equivalent primitive circuit . this is done by decomposing every n qubit gates ( where n @xmath12 3 ) into equivalent circuit comprising of elementary gates ( @xmath3 or @xmath4 quantum gates ) . we optimize the circuit comprising of quantum primitive gates in the following steps . 1 . we apply moving rule , deletion rule and modified template matching . in modified template matching a sequence of gates is substituted by another sequence of gates if it decreases the overall quantum cost of the circuit . in step 2 we have explained how a standard template matching reduces quantum cost by reducing the gate count . in modified template matching the overall cost is reduced by simultaneous application of template matching and introduction of new gates . here we may substitute a sequence of gates by a larger sequence of gates if after the substitution , the gates present at the edge of the new sequence merges with the adjacent gates on the same qubit lines to reduce the overall quantum cost . it is explained in example 1 of this section . we club together the adjacent gate / gates of dimension @xmath3 and @xmath4 , @xmath4 and @xmath3 , @xmath3 and @xmath3 , @xmath4 and @xmath4 to form new gates . in the circuit there may be other gates in the same qubit lines but not adjacent . in this step we will apply commutation rule and if the gates on the same qubit line or lines can be brought adjacent they will again form a new gate and reduce the cost . this is a modified optimization where we introduce new gate and apply the commutation rule to decrease the quantum cost of the circuit . since new gates are formed in the procedure , the existing gates in the circuit may belong to another gate library and it is possible that templates for that particular gate library exist , hence we explore the further scope of minimization of gate count by template matching and deletion rule . we may require generating new templates for this procedure . we remove those gates , which do not affect the output or in other words affect only the garbage bits . when we substitute toffoli gate by quantum primitives then there appear a lot of unnecessary quantum gates . this situation is similar to the garbage bits which are added to make an irreversible function reversible . analogously these gates can be called as garbage gates . for example , if during computation the desired output of the circuit is obtained from the third qubit line in fig . 2i then first two qubit lines at the output are garbage bits and the last two cnot gates are garbage gates . another example is a reversible function like 4mod5 @xcite ( grovers oracle ) whose output is 1 if the 4 bit input is divisible by 5 . the circuit has one desired output and rest of the output bits are garbage bits . in this case when we apply our quantum cost minimization algorithm we find it helpful to remove those gates ( garbage gates ) that affect only the garbage bits . this unique feature of quantum cost optimization algorithm is applied in the present work to minimize the cost of 4mod5 d1 circuit ( see table 1 ) . the quantum cost of entire circuit is obtained as the total number of quantum gates present in the circuit . to illustrate how this algorithm works let us consider following two examples . 1 . consider a fredkin gate and convert it to nct circuit by applying a synthesis algorithm @xcite as shown in fig . we will calculate its quantum cost in two parts which is without optimizing the nct circuit and after optimizing the nct circuit . in the first part we substitute the toffoli gate with its quantum primitives as shown in fig . 2b . in fig.2c we have applied moving rule and indicated the movement by arrows . there are two places as shown in fig . 2d where modified template matching can be applied and the resultant circuit is shown in fig . 2e , here we have also marked the places where we can again apply templates . we obtain a circuit shown in fig . 2f , we have marked in boxes the new gates and find that the quantum cost is 11 . in the second part we will optimize the nct circuit of fredkin gate in fig . 2a by applying template matching and obtain an optimized circuit as shown in fig . 2 g and further the toffoli gate is substituted by primitives shown in fig . we have applied modified optimization rule ( commutation is shown by arrow ) and in fig . 2i we have shown the new gates formed . the quantum cost of the circuit is 5 . this example clearly establishes that it is very essential to optimize the reversible circuit before substituting it with its quantum primitives . this aspect is not mentioned in earlier works @xcite . it also clearly explains the meaning of modified template matching protocol introduced in the present work . 2 . the reversible nct circuit for function 3_17 , is shown in fig 3a @xcite . this is the input of our algorithm , in fig 3b we have shown that the end cnot gate will commute with adjacent toffoli gate ( thereby reduce the quantum cost ) and the movement is shown by an arrow . the resultant circuit after commutation is shown in fig . we try to optimize its gate count but we find that we can not apply self inverse rule or template matching . we substitute the toffoli gate with its primitives and the resultant circuit is shown in fig . we try to optimize the circuit , there are two places shown in fig . 3e where templates can be applied and after the application of templates we have obtained the circuit which is shown in fig . 3f . thereafter we apply modified optimization technique in fig . 3 g , new gates are formed which are shown in boxes in fig . finally we calculate total number of quantum gates in the circuit and find the quantum cost of the circuit . we have already mentioned that most of the existing results related to quantum cost are available in benchmark page of maslov _ et al . _ @xcite and in revlib @xcite . in addition to these two databases mohammadi and eshghi @xcite , gupta _ et al . _ @xcite and maslov _ _ et al.__@xcite have independently reported the quantum cost of different reversible circuits . we have compared the quantum costs reported in these works with the quantum costs of the same functions obtained using the present algorithm . the results of comparison are shown in table 1 - table 3 . to be precise in table 1 we have compared the quantum costs of the following functions : i ) mod5 function which is divisibility checker , ii ) ham3 which is the size 3 hamming optimal coding function , iii ) ham7 which is size 7 hamming optimal coding function , iv ) hwb4 which is the hidden weighted bit function @xcite with parameter n=4 , v ) 3_17 which is the worst case scenario 3 variable function @xcite having function specification \{7 , 1 , 4 , 3 , 0 , 2 , 6 , 5 } and vi ) 4_49 which is the worst case scenario 4 variable function @xcite having function specification \{15 , 1 , 12 , 3 , 5 , 6 , 8 , 7 , 0 , 1 0 , 13 , 9 , 2 , 4 , 1 4 , 11}. here we would like to note that in this paper we have mentioned the circuits described in @xcite as benchmark circuits . to provide specific examples and to establish the superiority of our algorithm we have applied our algorithm to those benchmark circuits . further , the benchmark circuits reported in @xcite to realize a particular function is not unique and consequently different designs for the same purpose are marked with different indices , for example d1 denotes design 1 , d2 denotes design 2 etc . here we have followed the same convention as it is used in @xcite . _ @xcite have synthesized few reversible circuits for realization of above mentioned functions in the form of a network of toffoli gates and have also reported their quantum costs . further in @xcite improved quantum costs are reported for various circuits reported earlier @xcite . we have compared the quantum costs reported in these works in table 1 . in table 2 we have reported quantum cost of circuits from revlib @xcite . to be precise , we have compared quantum cost of the following functions : i ) miller gate , ii ) 3_17 which is the worst case scenario 3 variable function @xcite and iii ) different designs of decode 24 function which is 2 to 4 binary decoder . table 3 compares quantum costs of some circuits that has been reported in @xcite . for example : i ) two bit binary adder with carry input using one constant input ( see fig . 3a of @xcite ) , ii ) two bit binary adder with carry input using two constant input ( see fig . 3b of @xcite ) , iii ) 9 s complement circuit without constant inputs ( see fig . 4a of @xcite ) and iv ) @xmath3 bit multiplier ( see fig . 15 of @xcite ) . the algorithm may be applied to other benchmark circuits too but to do so either one has to develop templates for the corresponding gate library or convert the circuit into other gate library for which templates has been provided in literature example nct gate library . in table 4 , we have calculated quantum cost of some pure quantum circuits like epr , quantum teleportation and shor code . since quantum cost of these circuits have not been reported earlier , therefore its comparison could not be done . the quantum cost optimized circuits are shown in the first column of table 1 - table 4 . the gates shown in the dotted box should form a new gate and it would be counted as a single gate in the calculation of quantum cost . we have proposed an algorithm for minimization of quantum cost . we have applied our algorithm to different circuits from various sources @xcite and compared our results . the outcome of the comparison ( see table 1 - table 3 ) clearly shows that the proposed algorithm produces best result . in table 4 we have reported quantum cost of different quantum circuits ( for example , quantum teleportation , epr circuit etc . ) . through these examples it is clearly established that the proposed algorithm is useful in reduction of quantum cost . thus the present algorithm provides a window for reduction of quantum cost of other circuits in future . 47 r. landuer , irreversibility and heat generation in the computing process , _ ibm j. res . develop . _ * 5 * ( 1961 ) , 183191 . p. kerntopf , a new heuristic algorithm for reversible logic synthesis , _ in proceedings of the ieee design automation conference _ ( 2004 ) , 834837 . p. gupta , a. agarwal and n. k. jha , an algorithm for synthesis of reversible logic circuits , _ in proceedings on computer aided design of integrated circuits and systems _ * 25 * ( 2006 ) , 23172330 . a. younes , synthesis and optimization of reversible circuits for homogeneous boolean functions , _ quant - ph/0664v1 _ ( 2007 ) , 117 . c. h. bennet and g. brassard , quantum cryptography : public key distribution and coin tossing , _ in proceedings of the ieee international conference on computers , systems , and signal processing _ ( 1984 ) , 175179 . c. bennett and s. j. wiesner . communication via one- and two - particle operators on einstein - podolsky - rosen states . lett . _ * 69 * ( 1992 ) , 28812884 . m. perkowski _ et al . _ , a hierarchical approach to computer - aided design of quantum circuits , _ in 6th international symposium on representations and methodology of future computing technology _ ( 2003 ) , 201209 .
a new algorithm for minimization of quantum cost of classical reversible and quantum circuits have been designed . the quantum costs obtained using the proposed algorithm is compared with the existing results and it is found that the algorithm produces minimum quantum cost in all cases . * keywords : * quantum cost , circuit optimization and quantum circuit . jaypee institute of information technology university , noida , india
merkel cell carcinoma ( mcc ) is a rare neuroendocrine malignancy of the skin , initially named after friedrich merkel in 1875 . although merkel 's description of this tumor subtype was based on a description of moles,1 the true pathologic diagnosis was ultimately defined as a trabecular carcinoma of the skin almost 100 years later by cyril toker in 1972.2 the name is derived from the neurosecretory granules in the tumor cells that likely originate from the neural crest , derivative of merkel cells.3 after toker 's description , the number of mcc cases reported increased substantially , with an incidence of 44 per 100,000.4 mcc is more common in caucasians ( 94% ) , older populations ( average age of 72 years ) , and males ( men are two times more likely to be diagnosed than women).5 6 the most common location in tumor diagnosis is the head and neck , followed by the trunk and extremities . fifty - two percent of the patients have regional lymph node involvement at initial diagnosis , and 34% of this patient population presents with distant metastases.7 mcc has 5-year relative survival rates for localized , regional , and distant mcc of 75 , 59 , and 25% , respectively , with a mortality rate of 33% ( nearly twice that of metastatic melanoma).5 8 there are currently six reports in the literature of mcc causing metastatic epidural spinal cord compression ( mescc ) with four reports demonstrating survival of 1 to 4 months after surgical decompression and stabilization with or without chemotherapy and/or radiation.9 10 11 12 13 14 here we review the literature on mcc causing mescc , and we present the seventh case of mcc metastasis to the spine causing mescc . a 76-year - old man was diagnosed with mcc after biopsy of a skin lesion on his left upper back over the scapula . he subsequently had a wide excision , and a sentinel lymph node biopsy 2 months later revealed a 2.8-cm tumor and 4/8 lymph nodes were positive . he underwent complete axillary dissection 3 months after the diagnosis , followed by adjuvant external radiation therapy over the left scapula with a total dose of 50 gy in 200-cgy fractions , which ended 5 months after the diagnosis . he developed a recurrent tumor in the left axilla and the left anterior chest 10 months after the diagnosis . the patient underwent resection of these tumors 11 months after the diagnosis followed by 68 gy of radiation therapy that was completed 14 months after the diagnosis . prior to the admission for mescc , the patient ambulated with a walker at baseline and used an ankle foot orthotic on his left side for residual hemiparesis from a stroke in 1989 . the patient presented to the emergency room with right lower extremity weakness and difficulty with ambulation resulting in several falls over a 1- to 2-week period 16 months after initial diagnosis . he denied trauma , numbness , tingling , paresthesias , or urinary / bowel dysfunction . on neurologic exam , the patient 's left lower extremity motor strength was 1 to 2/5 throughout , and the right lower extremity was 4/5 , with upgoing toes and hyperreflexia . an mri demonstrated a t5 solitary epidural mass encasing and compressing the spinal cord that extended into the paraspinal muscles bilaterally , left greater than right , focused at the t5 vertebral body and extending from the midlevel of t4 with neural foraminal invasion to the middle of the t6 vertebral body ( fig . 1 ) . the patient underwent a t5 transpedicular approach for an intralesional resection through a corpectomy with cage placement and a t3t7 posterior spinal fusion because the bony destruction involved the entire vertebral body and posterior neural elements encasing the spinal cord ( fig . postoperatively , the patient 's motor exam improved to 3/5 in his left lower extremity ( baseline from a previous stroke ) and 5/5 strength in the right lower extremity , and he was able to ambulate with a walker again . pathologic examination demonstrated a metastatic neuroendocrine tumor consistent with his prior diagnosis of mcc . ( a ) sagittal and ( b ) axial magnetic resonance imaging demonstrating a metastatic merkel cell carcinoma tumor involving the vertebral body and encasing the spinal cord . ( a ) sagittal computed tomography scan and ( b ) thoracic spine radiograph demonstrating a t5 corpectomy and cage placement with t3t7 posterior fusion . three weeks postoperatively , as the patient was to begin postoperative radiation treatment , he developed new - onset weakness in his bilateral lower extremities . mri of the thoracic spine revealed new sites of metastatic disease at t2t3 and t6t11 with epidural compression at the t8 vertebral body . after discussion with the family , the patient was admitted to hospice care 6 weeks after his surgery . a 76-year - old man was diagnosed with mcc after biopsy of a skin lesion on his left upper back over the scapula . he subsequently had a wide excision , and a sentinel lymph node biopsy 2 months later revealed a 2.8-cm tumor and 4/8 lymph nodes were positive . he underwent complete axillary dissection 3 months after the diagnosis , followed by adjuvant external radiation therapy over the left scapula with a total dose of 50 gy in 200-cgy fractions , which ended 5 months after the diagnosis . he developed a recurrent tumor in the left axilla and the left anterior chest 10 months after the diagnosis . the patient underwent resection of these tumors 11 months after the diagnosis followed by 68 gy of radiation therapy that was completed 14 months after the diagnosis . prior to the admission for mescc , the patient ambulated with a walker at baseline and used an ankle foot orthotic on his left side for residual hemiparesis from a stroke in 1989 . the patient presented to the emergency room with right lower extremity weakness and difficulty with ambulation resulting in several falls over a 1- to 2-week period 16 months after initial diagnosis . he denied trauma , numbness , tingling , paresthesias , or urinary / bowel dysfunction . on neurologic exam , the patient 's left lower extremity motor strength was 1 to 2/5 throughout , and the right lower extremity was 4/5 , with upgoing toes and hyperreflexia . an mri demonstrated a t5 solitary epidural mass encasing and compressing the spinal cord that extended into the paraspinal muscles bilaterally , left greater than right , focused at the t5 vertebral body and extending from the midlevel of t4 with neural foraminal invasion to the middle of the t6 vertebral body ( fig . the patient underwent a t5 transpedicular approach for an intralesional resection through a corpectomy with cage placement and a t3t7 posterior spinal fusion because the bony destruction involved the entire vertebral body and posterior neural elements encasing the spinal cord ( fig . postoperatively , the patient 's motor exam improved to 3/5 in his left lower extremity ( baseline from a previous stroke ) and 5/5 strength in the right lower extremity , and he was able to ambulate with a walker again . pathologic examination demonstrated a metastatic neuroendocrine tumor consistent with his prior diagnosis of mcc . ( a ) sagittal and ( b ) axial magnetic resonance imaging demonstrating a metastatic merkel cell carcinoma tumor involving the vertebral body and encasing the spinal cord . ( a ) sagittal computed tomography scan and ( b ) thoracic spine radiograph demonstrating a t5 corpectomy and cage placement with t3t7 posterior fusion . three weeks postoperatively , as the patient was to begin postoperative radiation treatment , he developed new - onset weakness in his bilateral lower extremities . mri of the thoracic spine revealed new sites of metastatic disease at t2t3 and t6t11 with epidural compression at the t8 vertebral body . after discussion with the family , the patient was admitted to hospice care 6 weeks after his surgery . mescc is found in 5 to 10% of patients diagnosed with spinal column metastases and is associated with progressive disability secondary to the compression of the neural elements . decompressive surgery combined with radiation is the standard treatment for the tumors that are not highly radiosensitive and is shown to increase the efficacy in preserving neurologic function and to improve ambulation when compared with radiation therapy alone.15 16 the factors associated with a longer survival in patients with mescc were the ability to walk before and after therapy,17 18 19 a single site of epidural cord compression,20 a radiosensitive tumor histology,17 18 and no visceral or brain metastasis.21 here we present a case of mcc metastatic to the thoracic spine that had several factors consistent with a favorable prognosis and prolonged ambulatory status including a single site of epidural cord compression on presentation , radiosensitive tumor histology , and no evidence of visceral or brain metastasis on presentation . based on prior studies of metastatic disease to the spine , one could predict that the patient presented should have a more prolonged ambulatory status and possibly an improved prognosis ; however , despite the favorable factors previously mentioned , the patient developed progressive lower extremity weakness secondary to metastatic progression of his primary tumor . all of the prior cases of mcc metastasis to the spine demonstrated poor survival consistent with the study performed by allen et al ( table 1).9 10 11 12 13 14 22 in their review of 251 patients diagnosed with mcc , 14 of whom presented with distant metastasis , allen et al found that the 2-year survival rate was 11% with a 9-month median survival.22 the ability to predict the survival of patients with metastatic disease is critical in determining a management strategy . certain groups advocate for a greater than 3-month prognosis before recommending operative therapy,23 although others recommend greater than 6 to 7 months.24 25 although the prognosis threshold varies within the literature , the primary tumor subtype appears to be the most paramount factor in determining the patient prognoses before an operative intervention should be considered.15 25 in the six prior reports of mcc metastasis to the spine , by the time the primary tumor was detected in the spine , the prognosis was 9 months or less with an average survival of 3.5 months ( 5 of 6 patients died within 4 months ; table 1).9 10 11 12 13 14 given the dismal prognoses associated with rarer tumors such as mcc , further studies are needed to determine the most appropriate cutoff when operative intervention should be considered . in conclusion , mescc caused by mcc is rare with six reported cases in the literature.12 13 14 we report the seventh patient with mcc metastases to the spine and the fourth case showing neurologic decline in the setting of mescc requiring decompressive surgery . this is the first case of mcc that encased the spinal cord causing both anterior and posterior bony destruction that necessitated corpectomy with cage placement and posterior stabilization . in ambulatory patients presenting with spinal metastasis , acute neurosurgical decompression is the standard of care in patients presenting with a progressive decline in motor strength , ambulatory status , and/or bowel / bladder dysfunction . with such poor survival rates for patients diagnosed with mcc , although neurologic decline warrants aggressive treatment , the risks and benefits of a surgical intervention must be carefully considered . in certain tumor subtypes , the primary end point of ambulatory status may not be as useful in assessing whether surgical intervention is beneficial , and further studies are needed to determine the appropriate management paradigm for patients diagnosed with rarer metastatic primary tumors .
study design case report . objective merkel cell carcinoma is an aggressive neuroendocrine carcinoma with a poor prognosis . metastatic epidural spinal cord compression ( mescc ) is a debilitating disease causing neurologic deficits . the surgical management for mescc depends on pathology . methods we report a case of merkel cell carcinoma of the spine and evaluate the treatment paradigms utilized in the prior reports . result a 76-year - old man with a history of merkel cell carcinoma presented with 2-week history of progressive difficulty ambulating and a solitary t5 epidural mass encasing the spinal cord . the patient underwent a t5 corpectomy with cage placement and t3 to t7 posterior fusion with postoperative neurologic improvement and a return to ambulation . three weeks postoperatively , the patient re - presented with new - onset weakness and widespread metastatic spinal disease with epidural compression at the t8 level . six weeks postoperatively , he was placed in hospice care . conclusion prior reports in the literature demonstrated a poor prognosis for merkel cell carcinoma metastasis to the spine with survival ranging from 1 to 9 months after diagnosis . although neurologic decline necessitates a surgical intervention , the assessment of operative benefit should take into account the prognosis associated with the primary tumor subtype .
_ critical phenomena _ is the collective name associated with the physics of _ critical points _ @xcite , which is originated as a consequence of the divergence of the correlation length @xmath2 . the understanding of critical phenomena has motivated the development of new mathematical tools for the study of phase transitions ; such as the _ renormalization group theory _ , which has a significant impact in condensed matter and high energy physics @xcite . in this work , we present simple theoretical arguments and simulations that reveal new aspects in the understanding of critical phenomena . we show that _ the environmental influence can radically affect the critical behavior _ of systems , as example , to provoke a suppression of the divergence of correlation length @xmath1 and some of its associated phenomena as spontaneous symmetry breaking . our arguments are based on a framework of equilibrium fluctuation theory recently proposed @xcite . the main contributions of this approach are the derivation of a set of fluctuation theorems compatible with _ anomalous response functions _ @xcite as well as _ uncertainty relations involving thermodynamic quantities _ @xcite . for the sake of self - consistence of this paper , we firstly present a brief review of the so - called _ fundamental equilibrium fluctuation theorem _ and some of its most immediate consequences @xcite . after , this theorem will be considered to analyze the role of the environmental influence on critical phenomena . the results of this analysis will be illustrated studying the critical behavior 2d ising model . finally , we present some concluding remarks . the fundamental equilibrium fluctuation theorem ( eft ) : @xmath3 describes the relation between the system response functions and its fluctuating behavior @xcite . the quantity @xmath4 represents the _ response matrix _ : @xmath5 which characterizes the system response to the environmental influence ; whereas @xmath6 denotes a generalized force ( pressure , electric field , magnetic field , etc . ) and @xmath7 the corresponding generalized displacement ( volume , polarization , magnetization , etc . ) . besides , @xmath8 and @xmath9 are the system enthalpy and the internal energy , respectively ; while @xmath10 has been set as the unity . ] denotes the inverse temperature and @xmath11 , the partial derivative @xmath12 . the quantity @xmath13 is the _ self - correlation matrix _ that characterizes the system fluctuating behavior : @xmath14while the _ correlation matrix _ @xmath15 : @xmath16describes the existence of _ environmental feedback effects _ among the system macroscopic observables @xmath17 and the environmental control variables @xmath18 due to the underlying thermodynamic interaction . as expected , the amount of heat exchanged between the system and the environment at the equilibrium @xmath19 obeys the condition @xmath20 . eft ( [ efdt ] ) represents a suitable extension of the usual fluctuation theorem @xcite : @xmath21derived from the boltzmann - gibbs ( bg ) distributions : @xmath22 } { z\left ( \beta , y\right ) } \omega(u , x)dudx . \label{bg}\ ] ] here , @xmath23 is the system density of states , while @xmath24 is the partition function . eq.([oefdt ] ) , as example , contains the fluctuation relations : @xmath25where @xmath26 is the isobaric heat capacity , @xmath27 is the isothermal compressibility and @xmath28 is the isothermal magnetic susceptibility . despite the wide application in statistical mechanics , bg distributions ( [ bg ] ) have a restricted applicability due to the environmental inverse temperature @xmath29 and its generalized force @xmath30 are regarded as _ constant parameters_. such that restriction demands the consideration of a thermal contact with a bath with infinite heat capacity or a reservoir with an infinite number of particles , as other _ idealizations _ assumed in conventional applications ( usually attributed to the natural environment ) . in a general equilibrium situation , the internal state of the system acting as environment " is also perturbed by the underlying thermodynamic interaction . this is the origin of environmental feedback effects described by the correlation matrix @xmath15 in the extended eft ( [ efdt ] ) . conventional eft ( [ oefdt ] ) is only compatible with states with a positive definite response matrix @xmath31 . considering its particular fluctuation relations ( [ usual ] ) , this last requirement implies the positive character of the heat capacity @xmath32 , the isothermal compressibility @xmath33 and the magnetic susceptibility @xmath34 . remarkably , thermodynamics also supports the existence of states with _ negative heat capacities _ and other anomalous response functions , that is , a non - positive definite response matrix @xmath31 . mathematically , the existence of anomalous response is associated with the presence of states where the entropy @xmath35 is a _ non - concave function_. such a relationship comes from the possibility of expressing response matrix @xmath31 as follows : @xmath36 where @xmath37 is the entropy hessian : @xmath38 and the transformation matrix @xmath39 : @xmath40 moreover , the thermodynamic quantities @xmath41 and @xmath30 are also obtained from the entropy @xmath42 via the expressions : @xmath43 the states with anomalous response conform the so - called regions of _ ensemble inequivalence _ @xcite . physically , the anomalous response is a consequence of the incidence of _ non - extensive effects _ @xcite , as example , _ the presence of long - range interactions _ or _ the development of spatial non - homogeneities during the occurrence of discontinuous phase transitions _ @xcite . the presence of a long - range force as gravitation explains the existence of negative heat capacities in astrophysical systems @xcite . the development of _ interphases _ induces the existence of _ surface correlations _ , which are the origin of the negative heat capacities @xmath0 observed during the phase coexistence phenomenon @xcite . analogously , such surface correlations explain the anomalous states with _ negative susceptibility _ @xmath44 observed in a magnetic system below the critical temperature , which owe their origin to the formation of _ magnetic domains _ @xcite . direct consequences of the conventional eft ( [ oefdt ] ) are known @xcite : * the system fluctuating behavior is determined by its own response to the external conditions . * the stable states are those ones where the response matrix @xmath31 is also positive definite because of the self - correlation matrix @xmath13 is always positive definite . * the simultaneous divergence of some components of the response matrix and their corresponding correlation functions at the critical points , @xmath45 , which is related to the divergence of correlation length , @xmath46 . the presence of the correlation matrix @xmath47 in the extended eft ( [ efdt ] ) introduces the following radical changes in the previous implications : * the system fluctuating behavior depends both on its response functions and the nature of the environmental influence . * the stable states are those ones where @xmath48 is a positive definite matrix , with @xmath49 being the identity matrix . states with anomalous response functions can be thermodynamically stable under certain environmental conditions . * the divergence of the correlations functions @xmath50 and the correlation length @xmath1 can be suppressed by the environmental influence despite the divergence of some components of the response matrix @xmath51 at the critical point . the first and the second implications , together , claim that both _ the system fluctuating behavior and its thermodynamic stability depend on the nature of the environmental influence_. a trivial example is found in the case of the isolated system , where @xmath52 . clearly , there is no direct relation between the heat interchange and the heat capacity @xmath32 for this particular situation , which gives evidences about the restricted applicability of the fluctuation relation @xmath53 . for a better understanding , let us consider a particular system where the unique relevant observable is the internal energy @xmath9 . in this case , the eft ( [ efdt ] ) drops to the following energy - temperature fluctuation relation @xcite : @xmath54 which constitutes an extension of the fluctuation relation @xmath55 obtained from the gibbs canonical ensemble ( a special case of bg distributions ) : @xmath56 eq.([etfr ] ) is compatible with the existence of states with negative heat capacities @xmath0 as long as the correlation function @xmath57 obeyed the stability condition : @xmath58 the simplest scenario with non - vanishing correlated fluctuations , @xmath59 , is where the system is put in thermal contact with other short - range interacting system with a finite heat capacity @xmath60 . in this case , the second system ( environment ) experiences a temperature fluctuation @xmath61 whenever the system absorbs or releases the amount of energy @xmath62 . substituting this last expression into eq.([etfr ] ) , one obtains the self - correlation function of the internal energy @xmath9 : @xmath63 accordingly , the environmental heat capacity @xmath60 drives the system fluctuating behavior and imposes the standard microcanonical and canonical conditions in the asymptotic limits @xmath64 and @xmath65 , respectively . the stability condition ( [ stab ] ) leads to the so - called thirring s constraint @xmath66 necessary for the stability of negative heat capacities in the framework of short - range interacting systems @xcite . let us enter into the central discussion of this work : the implication of the extended eft ( [ efdt ] ) on critical phenomena . our interest is to analyze the thermodynamic behavior of a magnetic system when the same one is immersed into an environment with constant inverse temperature @xmath29 ; at the same time , it is put under the influence of an external magnetic field , @xmath67 , that _ experiences a non - vanishing magnetic feedback effect _ @xmath68 . this kind of environmental influence naturally appears when the magnetic field @xmath69 associated with the system magnetization @xmath70 affects the source of the external magnetic field @xmath67 and induces the existence of non - vanishing correlations @xmath68 . for the sake of simplicity , it has been assumed that the external magnetic field @xmath67 is weakly perturbed by the magnetization fluctuations , so that , this effect can be considered within the linear approximation @xmath71 ; where @xmath72 is the system size , @xmath73 , the expectation value of the external magnetic field @xmath67 , and @xmath74 , an effective coupling constant that characterizes the system - environment magnetic interaction . in the case of @xmath75 , it considers the equilibrium situation described by bg distributions ( [ bg ] ) . conversely , a value @xmath76 only ensures the constancy of the external magnetic field @xmath67 in average sense . the application of the extended eft ( [ efdt ] ) to this type equilibrium situation leads to the following relation for the susceptibility @xmath34 : @xmath77and therefore : @xmath78admitting an extensive growth of the susceptibility @xmath79 with @xmath72 as @xmath80 , it is possible to verify that the self - correlation of the external magnetic field behaves as @xmath81 . from the thermodynamic viewpoint , @xmath82 does not differ from @xmath75 when @xmath83 . however , the positive character of the self - correlation function @xmath84 now leads to the following condition of thermodynamic stability : @xmath85 according to eq.([flu1 ] ) , the self - correlation function of magnetization @xmath86 _ remains finite _ when @xmath87 as long as the coupling constant @xmath74 takes a positive value . consequently , there is no divergence of the correlation length @xmath88 for this special equilibrium situation . moreover , the consideration of a coupling constant with @xmath89 enables the access to _ diamagnetic states _ @xmath90 that exist below the critical temperature , which are schematically represented in fig . [ scheme.eps ] . let us suppose that the magnetic system is initially set at a state * o * in the line with zero magnetization at fig . [ scheme.eps].a , where @xmath91 and @xmath92 . considering that the environmental inverse temperature @xmath41 is increased with and without the magnetic feedback effect @xmath68 , a relevant question emerges : _ what is the system behavior under these two external influences _ ? the states with zero magnetization , @xmath93 , inside the region with @xmath94 are unstable within the bg distribution ( [ bg ] ) . in this case , the self - correlation function @xmath86 diverges for @xmath95 when the system approaches the critical point @xmath96 ( where @xmath87 ) . for @xmath97 , the system is forced to move along the stable symmetric curves @xmath98 or @xmath99 with non - vanishing magnetization , where it undergoes a spontaneous symmetry breaking . conversely , diamagnetic states @xmath94 turn stable choosing a positive value of the coupling constant @xmath100 . in this latter situation , the self - correlation function @xmath86 does not diverge when the system approaches the critical point @xmath96 . for @xmath101 , the system remains on the line with zero magnetization @xmath93 inside the region with @xmath94 , which implies a _ suppression of the spontaneous symmetry breaking_. thus , the system critical behavior can be modified by the environmental influence . noteworthy that the incidence of non - vanishing feedback effect @xmath68 can also force the divergence of the self - correlation function @xmath84 at an arbitrary state * p * inside the region with negative magnetic susceptibility . the occurrence of this phenomenon demands a coupling constant @xmath102 . thus , the simultaneous divergence of the correlation length @xmath2 and the response function @xmath79 is only admissible if @xmath95 , that is , in the framework of bg distributions ( [ bg ] ) . the previous analysis can be verified through appropriate monte carlo ( mc ) simulations . for this purpose , we consider the ising model on a square lattice @xmath103 with periodic boundary conditions , whose internal energy @xmath104 and magnetization @xmath105 , where @xmath106 and @xmath107 denotes the nearest neighbors sites . as the case of conventional metropolis importance sample @xcite based on the bg distributions ( [ bg ] ) , the present situation with @xmath108 can be implemented through the following acceptance probability @xmath109 for a mc step from the state @xmath110 to @xmath111 : @xmath112 , 1\right\ } , \label{u.ap}\]]where the magnetic field @xmath67 has an implicit dependence on the magnetization fluctuations . the magnetization dispersion @xmath113 can be employed to obtain the inverse susceptibility per particle as @xmath114 . along the monte carlo simulations with @xmath115 , the value of the coupling constant @xmath116 is redefined for each calculated point using the optimal value @xmath117 , which minimizes the total dispersion @xmath118 and satisfies the stability condition ( [ stab2 ] ) . a comparative study of monte carlo simulations with and without a magnetic feedback effect @xmath119 is shown in fig.[study.eps ] . according to results that we show in fig.[study.eps].c , the magnetization dispersion @xmath120 diverges at the critical point @xmath121 in monte carlo simulations with coupling constant @xmath95 . conversely , the same quantity remains finite when @xmath122 , which indicates a suppression of the _ long - range order _ associated with the divergence of correlation length @xmath123 . simultaneously , there exist a suppression of the spontaneous symmetric breaking , which is manifested in fig.[study.eps].a and fig.[study.eps].b as a persistence of diamagnetic states , @xmath44 , with @xmath124 for @xmath125 . remarkably , the absolute values @xmath126 of these negative susceptibilities are very large . the suppression of the spontaneous symmetric breaking is also manifested as a _ bifurcation _ of caloric curves and the inverse isothermal susceptibility @xmath127 at the critical point * c * shown in fig.[study.eps].b and fig.[study.eps].d , a fact that gives evidences to the different thermodynamic behavior of this system inside the region with negative susceptibilities . as already evidenced , the extended eft ( [ efdt ] ) reveals some new insights in the understanding on statistical physics . this theorem clearly distinguishes two different type of thermodynamic properties for a real system : the _ intrinsic properties _ and the _ relative ones_. examples of intrinsic properties are _ the response functions _ ( [ response ] ) , _ the state equations _ ( [ var.deriv ] ) , as well as any other information derived from the thermodynamics of the isolated system ; in particular , from the knowledge of the entropy @xmath42 . conversely , the relative thermodynamic properties depend on the environmental influence acting in a concrete equilibrium situation , as example , any information concerning to the system stability and its fluctuating behavior . the divergence of correlation length @xmath1 and its associated critical behaviors ( spontaneous symmetry breaking , critical opalescence , etc . ) take place at states with a _ marginal stability _ ( see in fig.[scheme.eps].a ) . since stability conditions , e.g. : eq.([stab2 ] ) , crucially depend on the environmental influence , _ any critical behavior is always a relative phenomenon_. hence , the divergence of any response function component @xmath128 is _ not an authentic critical behavior _ , but an _ intrinsic phenomenon _ that has nothing to do with the divergence of correlation length @xmath1 . the above remarks evidence that the consideration of bg distributions ( [ bg ] ) can potentially lead to some incorrect predictions about the system thermodynamical behavior ; overall , when one assumes these equilibrium distribution functions outside the context of its traditional applications . this could be the case of collective phenomena involving systems with long - range interactions as non - screened plasmas and astrophysical systems @xcite , or , the small and mesoscopic systems as the case of nuclear multifragmentation @xcite , where the existence of states with anomalous response is almost a rule rather than an exception . before end this section , we would like comment three possible application frameworks of our approach , which could deserve a special attention in future works . previously , this framework of fluctuation theory have been successfully applied to overcome slow sampling problems in monte carlo simulations associated with the incidence of discontinuous phase transitions @xcite . analogously , the suppression of divergence of correlation length @xmath1 at the critical point could be also employed to design new monte carlo algorithms to deal with difficulties associated with continuous phase transitions . the second application framework are the _ quantum theories at finite temperature _ @xcite , which exploit the analogy between the evolution operator @xmath129 and the statistical operator @xmath130 . in high energy physics , these formulations have been applied to study processes that took place at the early universe as a whole , as example , spontaneous symmetry breaking of electro - weak interactions . since these processes are special cases of critical phenomena , the application of present framework of fluctuation theory could reveal new insights in their understanding . finally , the analogy between electric and magnetic systems strongly suggests the existence of anomalous _ dia - electric states _ ( electric counterpart of diamagnetic states ) below critical temperature of a ferro - electric system , which should not be detected using experimental techniques based on boltzmann - gibbs distributions ( [ bg ] ) . we think that the ideas discussed in this work could inspire new experimental techniques to clarify the existence ( or nonexistence ) of these anomalous states . as discussed elsewhere @xcite , the presence of a hypothetic dia - electric medium favors the formation of cooper - pairs , a mechanism that triggers the development of _ high - temperature superconductivity_. l velazquez thanks the financial support of conicyt / programa bicentenario de ciencia y tecnologa psd * 65 * ( chilean agency ) . 0 stanley h. e. , _ introduction to phase transitions and critical phenomena _ ( clarendon press , oxford , 1971 ) .
recently , we have derived a fluctuation theorem for systems in thermodynamic equilibrium compatible with anomalous response functions , e.g. the existence of states with _ negative heat capacities _ @xmath0 . in this work , we show that the present approach of the fluctuation theory introduces new insights in the understanding of _ critical phenomena_. specifically , the new theorem predicts that the environmental influence can radically affect critical behavior of systems , e.g. to provoke a suppression of the divergence of correlation length @xmath1 and some of its associated phenomena as spontaneous symmetry breaking . our analysis reveals that while response functions and state equations are _ intrinsic properties _ for a given system , critical behaviors are always _ relative phenomena _ , that is , their existence crucially depend on the underlying environmental influence . pacs numbers : 05.20.gg ; 05.40.-a ; 75.40.-s
SECTION 1. SHORT TITLE. This Act may be cited as the ``Aligning Incentives for Better Patient Care Act of 2011''. SEC. 2. PERMITTING CERTAIN INCENTIVE PAYMENTS THAT PROMOTE QUALITY AND EFFICIENCY. (a) In General.--Section 1877(e) of the Social Security Act (42 U.S.C. 1395nn(e)) is amended by adding at the end the following new paragraph: ``(9) Incentive payments that promote quality and efficiency.--Any remuneration made, directly or indirectly, to a physician by a qualified hospital (as such term is defined in subsection (j)(2)) under the terms of a quality incentive agreement that meets the requirements of subsection (j)(1), for purposes of sharing cost savings generated for the hospital through the physician's voluntary participation in quality improvement activities under such agreement.''. (b) Requirements for Incentive Payments.--Section 1877 of the Social Security Act (42 U.S.C. 1395nn) is amended by adding at the end the following new subsection: ``(j) Requirements for Exception for Incentive Payments That Promote Quality and Efficiency.-- ``(1) Quality incentive agreement.-- ``(A) In general.--A quality incentive agreement that meets the requirements of this paragraph is an agreement between a physician and a qualified hospital that meets the following requirements: ``(i) Quality improvement activities.--The agreement lists the quality improvement activities under the hospital's quality improvement program that the physician agrees to participate in under the agreement. ``(ii) Determination of remuneration.--The agreement specifies that remuneration will be made to the physician by the hospital for cost savings achieved through the physician's participation in the quality improvement activities under clause (i), and includes the methodology that will be used to determine-- ``(I) the cost savings achieved through the physician's participation in such activities; and ``(II) subject to any limitation under paragraph (3)(A), the amount of any remuneration made to the physician under such agreement. ``(iii) Records.--The agreement contains a requirement that the physician and the hospital retain records related to the agreement, including records related to any remuneration made under the agreement, for a period determined by the Secretary. At the request of the Secretary, the physician and the hospital shall make such records available to the Secretary for purposes of an audit conducted by the Secretary under paragraph (3)(B). ``(B) Limitation on basis of payment.--The quality incentive agreement under subparagraph (A) may not allow remuneration to be made on the basis of-- ``(i) the volume of referrals made by the physician to the hospital; ``(ii) the value of referrals made by the physician to the hospital; ``(iii) cost savings achieved through limiting or denying a beneficiary's access to items or services solely on the basis that such services are new or improved; or ``(iv) cost savings achieved through directly or indirectly reducing or restricting the provision of items and services which the physician involved determines to be medically necessary or medically appropriate. ``(2) Qualified hospital.-- ``(A) In general.--For purposes of this subsection, the term `qualified hospital' means a hospital that-- ``(i) has established and maintains a quality improvement program that contains a list of quality improvement activities that meet the requirements of subparagraph (B) that the hospital seeks to encourage physicians to participate in; ``(ii) makes payments to the Secretary under subparagraph (C); ``(iii) provides notice to beneficiaries that meet the requirements under subparagraph (D); ``(iv) complies with the requirements of subparagraph (E), related to physician independence; and ``(v) submits the annual report required under subparagraph (F). ``(B) Quality improvement activities.-- ``(i) In general.--With respect to a quality improvement program of a hospital under subparagraph (A)(i), a quality improvement activity is an activity-- ``(I) that is designed by the hospital to-- ``(aa) improve the quality of inpatient hospital care (including improvements in patient safety); and ``(bb) generate cost savings for the hospital; and ``(II) does not jeopardize patient health or safety. ``(ii) Flexibility.--A quality improvement activity may be designed to-- ``(I) be clinical or non-clinical in nature; ``(II) increase communication and coordination between physicians and other providers; ``(III) improve admission planning, discharge planning, operating room utilization, timely documentation of the medical record, or appropriate transfer of patients within departments of a hospital; ``(IV) reduce the rate of avoidable re-operations; ``(V) reduce avoidable readmissions; ``(VI) appropriately reduce the average length of stay for patients in a hospital; or ``(VII) make other appropriate quality improvements, based on quality improvement measures recommended by physician specialty societies, the National Quality Forum, the National Committee for Quality Assurance, and the Physician Consortium for Performance Improvement. ``(iii) Other requirements.-- ``(I) Quality and cost benchmarks.--The hospital shall include the quality and cost benchmarks that the hospital uses to determine if an activity is a quality improvement activity in the quality improvement program under subparagraph (A)(i). ``(II) Limitation.--A quality improvement program may not include incentives to encourage the hospital or a physician to avoid taking on difficult or complex cases, which, but for the remuneration permitted under subsection (e)(9), the hospital or provider would have taken on. ``(C) Shared savings with medicare.--For each year (except for the first such year) that a hospital makes remuneration under subsection (e)(9), the hospital shall make, at such time and in such manner as the Secretary may require, a payment to the Secretary in an amount that is determined by the Secretary, but exceeds one percent of cost savings generated in such year as a result of physician participation in quality improvement activities through a quality incentive agreement under paragraph (1). Any payments made by a hospital to the Secretary under this subparagraph shall be deposited in the Federal hospital insurance trust fund. ``(D) Notice requirements.-- ``(i) In general.--A hospital that is a party to a quality incentive agreement under paragraph (1) shall, during the period of such agreement-- ``(I) provide notice to each beneficiary who receives inpatient hospital services in such hospital that the hospital provides remuneration to physicians who voluntarily participate in such agreement; and ``(II) disclose and prominently display on the public Internet website of the hospital information about the hospital's participation in such agreement and the remuneration made under such agreement. ``(ii) Timing.--To the extent that is feasible, without compromising patient safety, the notice under clause (i)(I) shall be provided to a beneficiary before such beneficiary receives inpatient hospital services through the hospital. ``(E) Protection of physician independence.--A qualified hospital may not-- ``(i) require that any physician who works for the hospital (as an employee, an independent contractor, or in any other status) to enter into a quality incentive agreement under paragraph (1); or ``(ii) penalize such physician (except through a denial of remuneration under subsection (e)(9), subject to the terms of the agreement under paragraph (1)) for the failure of such physician to participate in the quality improvement activities under the hospital's quality improvement program. ``(F) Annual report.--A hospital shall submit to the Secretary an annual report that includes-- ``(i) a copy of the hospital's quality improvement program; ``(ii) a list of the major quality improvement activities for which remuneration was made under any quality incentive agreement to which the hospital is a party during the previous year; ``(iii) the amount of cost savings generated for the hospital by such quality improvement activities during such year; and ``(iv) the quality improvement activities that generated the most cost savings for the hospital. ``(3) Responsibilities of the secretary.-- ``(A) Authority to set limits to prevent misuse of incentive payments.--The Secretary may set a limit to the amount of remuneration that a hospital may make to a physician under an agreement under paragraph (1) for the purpose of the types of remuneration prohibited under clauses (i) or (ii) of paragraph (1)(B). ``(B) Audits.--The Secretary, may, in such time and manner as the Secretary may specify, audit a hospital or physician with respect to remuneration made pursuant to a quality incentive agreement under paragraph (1). ``(C) Public disclosure of participating hospitals on website.--The Secretary shall maintain and publish a list of hospitals that have quality incentive agreements under paragraph (1) on the Medicare.gov Internet website of the Centers for Medicare & Medicaid Services.''. (c) Quality Incentive Ombudsman.--Section 1808(c) of such Act (42 U.S.C. 1395b-9(c)) is amended by adding at the end the following new paragraph: ``(4) Quality incentive ombudsman.-- ``(A) In general.--The Secretary shall provide a quality incentive ombudsman with Centers for Medicare & Medicaid Services, who shall respond to complaints and inquiries made by individuals described under paragraph (2)(A), hospitals, and physicians relating to the remuneration permitted under section 1877(e)(9). ``(B) Office and report.--The quality incentive ombudsman may be within the office of the Medicare Beneficiary Ombudsman appointed under paragraph (1), and the activities of the quality incentive ombudsman shall be included in the report under paragraph (2)(C).''. (d) Regulations.-- (1) In general.--Not later than January 1, 2014, the Secretary of Health and Human Services shall promulgate regulations to implement subsections (e)(9) and (j) of section 1887 of the Social Security Act, as added by subsection (a). Such regulations may include model quality incentive agreements and quality improvement programs. (2) Consultation.--In developing the regulations under paragraph (1), the Secretary of Health and Human Services shall consult with physician specialty societies, hospitals, and individuals entitled to benefits under part A or enrolled under part B of title XVIII of the Social Security Act. (3) Federal trade commission and department of justice.-- Not later than January 1, 2014, to the extent that quality incentive agreements under section 1877(j) of the Social Security Act may implicate anti-trust laws and regulations, the Federal Trade Commission and the Attorney General shall review such laws and regulations and shall issue regulations or guidance that includes examples of quality incentive agreements (as such term is used in section 1877(j) of the Social Security Act) that are permitted under such laws and regulations, and examples of such agreements that are not permitted under such laws and regulations. (e) Effective Date.--The amendments made by this section shall apply to remuneration made on or after January 1, 2014. SEC. 3. EXCEPTION TO CIVIL MONETARY PENALTIES FOR CERTAIN INCENTIVE PAYMENTS. Section 1128A(b)(1) of the Social Security Act (42 U.S.C. 1320a- 7a(b)(1)) is amended, in the matter preceding subparagraph (A), by inserting ``(except for remuneration made pursuant to section 1877(e)(9))'' after ``makes a payment''. SEC. 4. ESTABLISHMENT OF A SAFE HARBOR FROM CERTAIN CRIMINAL PENALTIES TO PROVIDE FOR USE OF INCENTIVE PAYMENT PROGRAMS BETWEEN PHYSICIANS AND HOSPITALS. Section 1128B(b)(3) of the Social Security Act (42 U.S.C. 1320a- 7b(b)(3)) is amended-- (1) in subparagraph (I), by striking ``and'' at the end; (2) in subparagraph (J), by striking the period at the end and inserting ``; and''; and (3) by adding at the end the following: ``(K) any remuneration between a hospital and a physician made pursuant to section 1877(e)(9).''.
Aligning Incentives for Better Patient Care Act of 2011 [sic] - Amends title XVIII (Medicare) of the Social Security Act to: (1) except from the prohibition against certain physician referrals and other compensation any incentive payments promoting quality and efficiency that are made under a quality incentive agreement between a physician and a qualified hospital, (2) prescribe requirements for such agreements, and (3) direct the Secretary of Health and Human Services (HHS) to provide a quality incentive ombudsman with the Centers for Medicare & Medicaid Services. Amends SSA title XI to exempt such incentive payments from certain civil money penalties as well as from criminal penalites for illegal remunerations.
urinary tract infection is the most common febrile illness in pediatric second to otitis media and pharyngitis . it accounted for 10% of all febrile illnesses in children ( 1 , 2 , 3 ) . long - term complications of urinary tract infection in children include unilateral renal parenchymal defect and unilateral kidney retarded growth . the glomerular filtration rate and blood pressure do not change indicating a very low for serious renal damage ( 4 ) . it is more common in preterm babies ( 4 - 25% ) than term ones ( 1% ) ( 5 ) . in early life , it is more common in males than female then it decline rapidly in the prepubertal life girls experienced more episodes of utis than males , 8% compared to 2% respectively ( 6 , 7 ) . escherichia coli for many years remain the most common isolates causing uti in children ( 6092% ) . enterococcus ( 8 - 10 ) . diagnosis of uti may in children is simple usually urine analysis and cultures are enough to establish the diagnosis . the development of multidrug resistance strains makes treatment issue among the most controversial issues in children . in africa , utis in children is a common and complex problem due to co - infection with other febrile illnesses ( 11 ) . high frequency rate of infection was reported by many authors due to co - existence of multiple risks factors . in sudan , the aim of this study was to identify uropathogens responsible for urinary tract infection in children fewer than 5 years of age , and determine the antibiograms of the uropathogens to commonly used antibiotics . moreover , to provide the foundation for prevention programs , and making policy decisions . this prospective cross - sectional study was conducted at gadarif teaching hospital , in gadarif state , eastern sudan , during the period from june 2011 to june 2012 . it is the biggest hospital of the state and there are 800 beds to maintain health services for the whole gadarif state . a total of 304 children under 5 years of age who fulfilled criteria for case definition of uti were included in the study . inclusion criteria were children under 5 years of age who suffered from ( dysuria ) , ( fever and dysuria ) , ( dysuria and vomiting ) , ( dysuria , fever and vomiting ) , ( polyuria and suprabubic pain ) , ( fever ) , ( fever and vomiting ) , ( fever and diarrhea ) , ( fever , vomiting and diarrhea ) , ( vomiting ) , ( vomiting and diarrhea ) or ( diarrhea ) were eligible to be enrolled in the study ( 12 ) . children excluded from the study , were those already on antibiotic or known to suffer from other underlying conditions . less than 3 years of age the specimens were collected by a disposable apparatus consisting of a plastic bag with an adhesive backing around an opening that can be fastened to the perineal area or around the penis to permit direct voiding into the bag . the specimen bag was carefully removed , and the urine transferred to a sterile urine container . then the collected urine was analyzed immediately ( fischbach and dunning , 2004 ) ( 13 ) . for children above the age of 3 years 3 - 5 ml of urine wet film of urine deposits were microscopically examined for pus cells , rbcs , crystals , cast , bacterial cells . finding of more than 5 white blood cells per high - power field in centrifuged fresh urine was considered a satisfactory positive screening test for uti ( 15 ) . semi - quantitative method was done byusing a calibrated loop ( 0.001ml ) of un centrifuged urine , a loopfull was spread on cystine lactose electrolyte deficient ( cled ) agar . this cled was incubated aerobically over night at 37 c if no growth further incubation for 48 hours , the growth of 100 colony forming units by this method indicates the presence of 10 bacteria per ml of urine ( michael l et . the bacterial growth estimation of ( 10)bacteria per ml or more was considered uti ; a count of 10.00049.000bacteria/ ml was considered significant with a signs of acute infection ( presence of pyuria ) . bacteriological identification for significant specimen on presumptive colony was identified using : colonial morphology ( 16 ) , gram stain ( 17 ) , and biochemical test s such as : indole , citrate , oxidase , h2s production , mrvp , lactose fermentation , urea hydrolysis , gas production , catalase , coagulase previously discuss by bartet al . ( 18 ) . analytical profile index ( api-20e ) system was performed for confirmation of identification as previously mentioned by ( ahmed mi , 2012 ) to identify members of the family enterobacteriaceae and associated organisms ( biomerieux , inc . the disc diffusion method were employed by standardize filter paper discs impregnated with fixed amounts of antimicrobial drugs . the urine sample was collected by two different techniques . for children less than 3 years of age the specimens were collected by a disposable apparatus consisting of a plastic bag with an adhesive backing around an opening that can be fastened to the perineal area or around the penis to permit direct voiding into the bag . the specimen bag was carefully removed , and the urine transferred to a sterile urine container . then the collected urine was analyzed immediately ( fischbach and dunning , 2004 ) ( 13 ) . for children above the age of 3 years 3 - 5 wet film of urine deposits were microscopically examined for pus cells , rbcs , crystals , cast , bacterial cells . finding of more than 5 white blood cells per high - power field in centrifuged fresh urine was considered a satisfactory positive screening test for uti ( 15 ) . semi - quantitative method was done byusing a calibrated loop ( 0.001ml ) of un centrifuged urine , a loopfull was spread on cystine lactose electrolyte deficient ( cled ) agar . this cled was incubated aerobically over night at 37 c if no growth further incubation for 48 hours , the growth of 100 colony forming units by this method indicates the presence of 10 bacteria per ml of urine ( michael l et . the bacterial growth estimation of ( 10)bacteria per ml or more was considered uti ; a count of 10.00049.000bacteria/ ml was considered significant with a signs of acute infection ( presence of pyuria ) . bacteriological identification for significant specimen on presumptive colony was identified using : colonial morphology ( 16 ) , gram stain ( 17 ) , and biochemical test s such as : indole , citrate , oxidase , h2s production , mrvp , lactose fermentation , urea hydrolysis , gas production , catalase , coagulase previously discuss by bartet al . ( 18 ) . analytical profile index ( api-20e ) system was performed for confirmation of identification as previously mentioned by ( ahmed mi , 2012 ) to identify members of the family enterobacteriaceae and associated organisms ( biomerieux , inc . the disc diffusion method were employed by standardize filter paper discs impregnated with fixed amounts of antimicrobial drugs . a total of 304 ( 100% ) children suffering from utis with the mean age 1.971.061 years were included in this study . the majority of these children 203 ( 66.7 % ) were less than two years of age , and more than half of them were male 174 ( 57.2% ) . significant pyuria and bacteriuria was detected in 47.7 % ( n=145 ) of the total studied subjects ; in 250 ( 82.2% ) no potential pathogens were isolated . the frequency of uti was also equal in urban and rural settings ( 51% vs. 49% ) . the majority 46.3 % ( n=25 ) of subjects were less than 1 year of age , followed by age group 1 to 2 years 20.4%,and 16.7% for both 2 to 3 and more than 3 years of age . the most common bacterial isolates were escherichia coli - 23 ( 42.6% ) followed by pseudomonas aeruginosa -16 ( 29.6% ) , klebsiellapneumoniae - 10(18.5% ) , and proteus mirabilis - 5 ( 9.3% ) as identified by conventional biochemical tests figure 1 . furthermore , the rapid and accurate test of identification organisms ( api identification system ) for enterobacteria used to confirm the conventional identification methods results showed typical results . types of bacterial isolates in males , the predominant uropathogens during the first year of life was klebsiella pneumonia 46.7 % , while e.coli and proteus mirabilis constituted 13.3% of isolates for each , after the first year of life the escherichia coli isolates predominated 100% figure 2 . distribution of uropathogens in males according to age group in females , both escherichia coli and pseudomonas aeruginosa were the predominating isolates up to 5 years with few proteus mirabilis infection figure 3 . distribution of uropathogens in females according to age group the antimicrobial susceptibility of all isolates is shown in tables 1a and 1b . e. coli isolates was resistance against ; augmentin 91.3% , cotrimoxazole 100% , cephalexin 95.7% , and nalidixic acid 26.1% . however e. coli isolates were highly susceptible to norofloxacin91.3% , ciroflxacin 87% and nitrofurantoin 73.9% intermediate sensitivity is shown on the tables . uropthogens and their susceptibility to antimicrobials agents in children with urinary tract infection uropthogens and their susceptibility to antimicrobials agents in children with urinary tract infection ps.aeruginosa was shown resistant against ; cephalexin 81.2% , co - trimoxazole 62 , 5% , nitrofurantoin 75% , augmentin56.2% and ceftriaxone43.8% . on other hand ps.aeruginosa isolates were susceptible ; to ciprofloxacin 75% , and norfloxacin 68.8% . both k.pneumoniae and pr.mirabilis were high susceptible ; to ciprofloxacin ( 100%),and ( norofloxacin ) 100% . e. coli isolates was resistance against ; augmentin 91.3% , cotrimoxazole 100% , cephalexin 95.7% , and nalidixic acid 26.1% . however e. coli isolates were highly susceptible to norofloxacin91.3% , ciroflxacin 87% and nitrofurantoin 73.9% intermediate sensitivity is shown on the tables . uropthogens and their susceptibility to antimicrobials agents in children with urinary tract infection uropthogens and their susceptibility to antimicrobials agents in children with urinary tract infection ps.aeruginosa was shown resistant against ; cephalexin 81.2% , co - trimoxazole 62 , 5% , nitrofurantoin 75% , augmentin56.2% and ceftriaxone43.8% . on other hand ps.aeruginosa isolates were susceptible ; to ciprofloxacin 75% , and norfloxacin 68.8% . both k.pneumoniae and pr.mirabilis were high susceptible ; to ciprofloxacin ( 100%),and ( norofloxacin ) 100% . in this study , of all subjects with significant pyuria ( 145 , 47.7% ) , 54(17.8% ) had positive bacterial growth . the risk of developing utis in these children under was almost equal among males ( 51.9% ) and females ( 48.1% ) and rural and urban residency was similarly affected . the majority of subjects 36 ( 66.7 % ) were less than two years of age . e. coli ( 42.6% ) was the most predominant uropathogen , sensitive to ciprofloxacin ( 91.3% ) , followed by pseudomonas aeruginosa ( 29.6% ) sensitive to ciprofloxacin ( 75% ) and norfloxacin ( 68.8% ) , klebsiellapneumoniae ( 18.5% ) sensitive to ciprofloxacin and norfloxacin and nalidixic acid ( 90% ) and proteus mirabilis sensitive to ciprofloxacin and norfloxacin ( 90% ) , amoxicillin / clavulanic acid ( augmentin(80% ] . furthermore , the study showed that the incidence of first episode of utis was similar in both sexes in during the first year of life and thereafter , females had the higher incidence of utis than males . studies from sweden have shown similar findings ( 19 , 20 ) . this study documented a high frequent occurrence of urinary tract infections ( 17.8% ) , and bacteremia among febrile under - fives attending maternity and children hospital gadarif , eastern sudan . this finding does not represent the true prevalence of utis in gadarif district because the nature of the study was a hospital - based , only patients with severe disease and those who live nearby reported to the hospital while those living far or have financial constraints , or lack of transportation . empirical treatment of all fever with antibiotics and antimalarial is a common practice in the developing nations . a higher prevalence rate ( 20.3% ) of utis was reported in afric ( 21 ) . frequency of utis in the developing countries is very high than 3.3% and 9% rates quoted from developed countries ( 22 , 23 ) . it has been found that the earlier the development of utis in life , the higher chance of developing recurrent utis , furthermore , the risk of recurrent utis increased significantly when the first infection is caused by a non - e . , we found that the dominant uropathogen was e. coli followed by pseudomonas aeruginosa , klebsiellapneumoniae and proteus mirabilis . in sudan , a similar study conducted on adult populations showed that e. coli of least occurrences ( 6% ) , while the dominant organism was p. aeurginosa ( 37% ) ( 26 ) . our findings are in agreement with some previous studies , which have shown that escherichia coli were the commonest organism isolated from urine samples ( 24 , 27 ) . furthermore , and in a study it was found that it accounted for 75% of all utis in all pediatrics of all age group followed by klebsiellapneumoniae , proteus mirabilis and pseudomonas aeruginosa ( 28 , 22 ) . a recent study examined the pathogens and their susceptibility in the first episode of utis showed that 96.1% of the isolate were escherichia coli with high susceptibility to aminoglycosides , ciprofloxacin and nitrofurantoin ; third generation cephalosporins , and low susceptibility to cephaloxin ( 29 ) . e. coli isolates in this study were highly sensitive ( near 100% ) to ciprofloxacin , norfloxacin , and nalidixic acid . unfortunately , it showed high resistant to commonly used antibiotics ( augmentin , cephalexin and -trimoxazole ) ( near 100% ) . similar findings from tanzania reported that e. coli is the dominant organism as a cause of utis in children under - fives , and it is sensitive to fluoroquinolones and resistant to third- and fourth - generation cephalosporin s ( 1 ) . similar studies were concluded in marrakech and in kashmir ( 31 ) concluded that escherichia coli were the most predominant isolate , followed by klebsiellapneumoniae and pseudomonas aeruginosa . however , they differ in the antibiotic sensitivity pattern , in marrakech third generation cephalosporin s and aminosides kept their effectiveness on the majority of isolates were the most effective treatment while , in the latter study , e. coli isolates were fully sensitive to ofloxacin , and cefuroxime . the high sensitivity to ciprofloxacin in this study may be explained by the fact that it is not one the commonly used drug for children due to their questionable safety in children . the development of multi - drugs resistance ( mdr ) to commonly used antibiotics in the developing world could be due to drug misuse , this misuse over time , will lead to greater levels of mutation in bacteria , leading to high levels of bacterial resistance . moreover , antibiotics are used as growth promoters to control infectious disease may lead to the development of mdr due to change in the genetic composition of bacteria . in this study , pseudomonas aeruginosa was found to be resistant to many antibiotics , and only appreciable susceptibility was found with ciprofloxacin and norfloxacin ( near70% ) . many studies have demonstrated that pseudomonas aeruginosa is becoming multi - drug resistant organism ( 31 , 32 ) . furthermore , results from united states and european hospitals indicated that pseudomonas aeruginosa exhibited lower susceptibility rates to many antimicrobial drugs in europe compared to ) compared to usa(33 - 35 ) . there is no report on current literature showed there are satisfactory antimicrobials that provided a satisfactory coverage for this organism . this means that treatment of uti in the absence of susceptibility will results in long - term complications of utis and the emergence of multi - resistant organisms . antibiotic resistance rates in uropathogens are rapidly growing , especially with regard to e. coli infections . for all uropathogens culture and sensitivity of the isolates remains the only solution to decrease multi - drug resistance strains , and it should be done as a routine before advocating the therapy . antibiotic abuse is of serious concern in the developing world , and a restriction of their uses in the community to a retard development of further drug resistance is important . drug - resistant e. coli are readily acquired through the food and water ; therefore , public and personal hygiene are the essential component of this circuit . the most common uropathogens were e. coli , pseudomonas aeruginosa , klebsiellapneumoniae , and proteus mirabilis .
background : childhood urinary infections are among the most common febrile illnesses occurring during this period with varying susceptibility to antibiotic.aim:the aim of this study was to identify uropathogens responsible to for urinarytract infection ( utis ) in children less than 5 years of age , and determine the antibiograms of the isolates to commonly used antibiotics.patients and methods : hundred and four children ( 2 months - 5 years old ) seen at the gadarif teaching hospital from january 2012 and december 2013 were evaluated . a urine specimen was obtained by a plastic bag with an adhesive backing around an opening or by direct voiding into sterile container . urine was examined microscopically and those with significant pyuria and bacteruria were further cultured and microorganisms were identified and tested for antimicrobial susceptibility.results:out of 304 children suffering from utis ; 145(47.7% ) had significant pyuria of them ; 54(17.8 % ) had positive bacterial growth . the frequency of sex and residency were almost the same . e. coli ( 42.6% ) was the most common uropathogen , sensitive to ciprofloxacin ( 91.3% ) , followed by pseudomonas aeruginosa ( 29.6% ) sensitive to ciprofloxacin ( 75%)and norofloxacin ( 68.8% ) , klebsiellapneumoniae ( 18.5% ) sensitive to ciprofloxacin and norofloxacin and nalidixic acid ( 90% ) and proteus mirabilis sensitive to ciprofloxacin and norofloxacin ( 90% ) , amoxicillin / clavulanic acid ( augmentin(80%).conclusion : the most common uropathogens were e. coli , pseudomonas aeruginosa , klebsiellapneumoniae , and proteus mirabilis . ciprofloxacin is the recommended initial empirical therapy while awaiting the culture and sensitivity results .
SECTION 1. SHORT TITLE. This Act may be cited as the ``Small Business High Technology Entrepreneurship Act of 2001''. SEC. 2. FINDINGS AND PURPOSE. (a) Findings.--Congress finds the following: (1) The United States is uniquely positioned to benefit from the development and commercialization of technology resulting from the development of biosciences, information technology, and electronic technology. (2) Advances in biosciences, information technology, and electronic technology will create new products, services, and businesses, leading to high paying jobs and economic growth. (3) Technology networks are becoming necessary tools for businesses in the United States because of their ability to efficiently transfer information. (4) The development of biotechnology has produced processes such as 3-dimensional volume visualization and advanced signal processing which will help revolutionize both medical diagnostics and surgery. (5) The ability of the electronic industry to rapidly develop and manufacture measuring devices, sensors, semiconductors, and other electronic components is an essential component to providing for the national security of the United States. (6) The bioscience, information technology, and electronic technology sectors of the economy have all produced important products, services, and businesses. (7) Building on past gains in these sectors is vital to growing the United States economy, promoting health, and increasing educational opportunities. (b) Purpose.--The purpose of this Act is to enable small business concerns engaged in biotechnology, computer technology, and electronics to produce essential new products, businesses, employment opportunities, and economic growth through technological innovation. SEC. 3. TECHNOLOGY DIRECT LOAN PILOT PROGRAM. (a) In General.--The Administrator of the Small Business Administration may make direct loans under section 7(a) of the Small Business Act (15 U.S.C. 636(a)) to technology-related small business concerns located in a technology region. (b) Special Rules.--Notwithstanding the requirements of section 7(a) of the Small Business Act (15 U.S.C. 636(a)), the following special rules apply to loans described in subsection (a): (1) Amount of loans.--The Administrator may make such a loan to a small business concern if the total amount outstanding and committed to such concern under subsection (a) of this section and section 7(a) of the Small Business Act (15 U.S.C. 636(a)) would not exceed $5,000,000. (2) Technological consultation.-- (A) In general.--In evaluating each application for such a loan, the Administrator shall consult with, and give considerable weight to the assessments, recommendations, and conclusions of, the regional technology consultant regarding the technological feasibility and commercial viability of the applicant's business plan, including any technological research or development involved in such plan. (B) Selection of regional technology consultants.-- The Administrator shall select 1 non-profit organization located in each technology region to serve as the technology consultant for such region. In selecting each regional technology consultant, the Administrator shall ensure that such consultant has knowledge and experience in evaluating the technological feasibility and commercial viability of business plans of technology-related small business concerns. (3) Rule for resolving reasonable doubts.--Recognizing that greater risk may be associated with such loans, any reasonable doubt regarding the soundness of the applicant's business plan (including the feasibility and viability of any technological research or development involved in such plan) or the soundness of the loan for purposes of section 7(a)(6) of the Small Business Act (15 U.S.C. 536(a)(6)) shall be resolved in favor the applicant. (c) Termination.--The Administrator may not make a loan pursuant to the special rules of this section after the end of the 2-year period beginning on the date of the enactment of this Act. (d) Annual Reports.--In any year during which the Administrator is authorized to make loans under this section, the Administrator shall submit to Congress a report regarding the technology direct loan pilot project conducted under this section. Such report shall include-- (1) a list of the technology-related small business concerns approved for loans under this section during such year and the amounts of such loans; (2) recommendations for legislation that would improve the pilot project; and (3) recommendations regarding the expansion of the pilot project to additional technology regions or for an additional period of time. (e) Definitions.--For purposes of this section: (1) Administrator.--The term ``Administrator'' means the Administrator of the Small Business Administration. (2) Regional technology consultant.--The term ``regional technology consultant'' means the technology consultant selected by the Administrator under subsection (b)(2)(B) for a technology region. (3) Small business concern.--The term ``small business concern'' has the meaning given such term in section 3(a) of the Small Business Act (15 U.S.C. 632(a)). (4) Technology region.--The term ``technology region'' describes each of the following regions: (A) Nassau and Suffolk Counties in New York. (B) Santa Clara and Santa Cruz Counties in California. (5) Technology-related small business concern.--The term ``technology-related small business concern'' means any small business concern primarily engaged in one or any combination of the following: (A) Developing, producing, assembling, or manufacturing electronic components, computer hardware, or computer software; or (B) The biotechnology industry.
Small Business High Technology Entrepreneurship Act of 2001 - Authorizes the Administrator of the Small Business Administration (SBA) to make direct loans under the Small Business Act to technology-related small businesses located in a technology region. Allows such a loan if the total amount of SBA loans to such business does not exceed $5 million. Requires the Administrator, in evaluating each loan applicant, to consult with and give considerable weight to the assessments, recommendations, and conclusions of the regional technology consultant regarding the technological feasibility and commercial viability of the applicant's business plan for the use of such funds, including any technological research or development involved. Requires the Administrator to select one nonprofit organization in each technology region to serve as such consultant.
networks are the simplest representation of complex systems of interacting parts . examples of these are ubiquitous in practice , including large social networks @xcite , information systems @xcite and cooperate ownerships @xcite , to name just a few . despite a seemingly plain form , real - world networks reveal characteristic structural properties that are absent from regular or random systems @xcite . thus , networked systems are believed to be controlled by common phenomena . scale - free degree distributions @xcite , small - world phenomena @xcite , degree mixing @xcite ( i.e. , degree correlations at links ends ) and existence of communities @xcite ( i.e. , densely linked groups of nodes ) are perhaps among most widely analyzed properties of large real - world networks . note that community structure implies assortative ( i.e , positively correlated ) mixing by degree @xcite , which can be seen as a tendency of hubs ( i.e. , highly linked nodes ) to cluster together . the above are also the properties captured by many random graph models proposed in the literature @xcite . however , most ( non - social ) networks deviate from this figure . biological and technological networks are in fact degree disassortative ( i.e. , negatively correlated ) , while different information networks often reveal no clear degree mixing @xcite ( see figure [ fig : cora ] ) . thus , we here propose an evolving random graph model based on the link copying mechanism @xcite . each newly added node explores the network using the burning process in @xcite , while links of the visited nodes are copied independently of the latter . the model generates scale - free small - world networks with community structure and also degree disassortativity . furthermore , it has a natural interpretation for citation networks . the above process imitates an author of a paper including references into the bibliography ( i.e. , its citation dynamics ) , which enables different practical applications in bibliometrics ( see section [ sec : cora ] ) . data mining part of _ cora_citation network @xcite with highlighted hubs ( i.e. , @xmath0 of most highly linked nodes ) that are scattered across the network . ( node sizes are proportional to degrees . ) ] the rest of the paper is structured as follows . section [ sec : model ] introduces the proposed ( citation ) model , while a thorough analysis is given in section [ sec : experiments ] . section [ sec : conclusion ] concludes the paper . let a network be represented by a simple graph @xmath1 , where @xmath2 is the set of nodes , @xmath3 , and @xmath4 is the set of links , @xmath5 . next , let @xmath6 be the set of neighbors of node @xmath7 and let @xmath8 be its degree , @xmath9 . last , let @xmath10 be the mean degree and @xmath11 the mean neighbor degree . proposed graph model is based on the burning process of forest firemodel @xcite , which we introduce first . due to simplicity , the model is presented for undirected networks . let @xmath12 be the burning probability , @xmath13 ( see below ) . initially , the network consists of a single node , while for each newly added node @xmath14 , the burning process proceeds as follows . 1 . @xmath14 chooses an ambassador @xmath15 uniformly at random ( we say that @xmath14 burns @xmath16 ) and links to it . @xmath14 randomly selects ( at most ) @xmath17 neighbors of @xmath16 that were not yet burned @xmath18 and links to them . ( @xmath17 is sampled from a geometric distribution with mean @xmath19 . ) @xmath20 are taken as the ambassadors of @xmath14 ( step ( 2 ) ) . since each node can be visited at most once , the burning process surely converges . thus , to generate a network with @xmath21 nodes , the model repeats the above procedure @xmath22 times . forest firemodel produces shrinking diameters and densification phenomena observed in temporal networks @xcite . furthermore , generated networks are scale - free and small - world , and reveal a pronounced community structure . however , in contrast to many real - world networks , the model gives degree assortative networks ( see section [ sec : experiments ] ) . the model also has a natural interpretation for citation networks . burning process imitates an author of a paper including references into the bibliography ( i.e. , citation dynamics ) . author first reads a related paper , or selects the paper that triggered the research , and cites it ( step ( 1 ) ) . author then considers its bibliography for other related papers ( step ( 2 ) ) . some of these are further considered and also cited , while the author continues as before ( step ( 3 ) ) . nevertheless , forest fire model fails to reproduce some of the properties of citation networks ( e.g. , degree mixing ) . note that the described process assumes that authors read , or at least consider , all the papers they cite . however , this is indeed not the case @xcite . for example , seminal work on random graphs conducted by erds and rnyi @xcite is perhaps among most widely cited papers in network science literature . although , presumably , only a smaller number of authors have actually read the original paper . as the work is widely discussed elsewhere , most authors have just copied the reference from another paper . on the other hand , authors also do not cite all the papers they read , though related to their work . this can be simply due to space limitations . nevertheless , a paper can still be read thoroughly , with many of its references further considered and cited . examples suggest that the papers that authors read or cite are selected due to two , not necessarily dependent , processes . we thus propose a citationmodel that adopts the above burning procedure to traverse the network , while the links are formed according to another independent process . let @xmath23 be the linking probability , @xmath24 ( see below ) . initially , the network consists of a single link , while for each newly added node @xmath14 , the model proceeds as follows . 1 . @xmath14 chooses an ambassador @xmath15 uniformly at random . @xmath14 randomly selects ( at most ) @xmath17 neighbors of @xmath16 that were not yet burned @xmath18 . @xmath14 randomly selects ( at most ) @xmath25 neighbors of @xmath16 that were not yet linked @xmath26 and links to them . 4 . @xmath20 are taken as the ambassadors of @xmath14 ( step ( 2 ) ) . details are the same as before . again , the process surely converges , while the entire procedure is repeated @xmath27 times . let @xmath28 be the mean number of burned nodes ( i.e. , ambassadors ) . a node selects @xmath19 ambassadors on each step , thus , @xmath29 a node will fail to form any link ( i.e. , become isolated ) with probability @xmath30 . although isolated nodes are a common property of real - world networks , they are often ignored in practice or the network is even reduced to the largest connected component . thus , for the analysis here , we repeat the procedure until the largest component has @xmath21 nodes . since a node forms @xmath31 links on each step , expected network degree is ( with @xmath32 correction for isolated nodes ) @xmath33 although equations ( [ equ : burned ] ) and ( [ equ : degree ] ) are only valid in the limit of large network size , the bounds are rather tight for large enough @xmath21 ( see figure [ fig : analysis ] ) . thus , given network degree @xmath10 and fixed @xmath34 , one can solve the system for @xmath12 , which can be used for parameter estimation in practice ( see section [ sec : cora ] ) . citation model generates small - world networks with scale - free degree distribution and community structure ( see section [ sec : analysis ] ) . furthermore , in contrast to forest firemodel , resulting networks are degree disassortative . we stress that the key factor here is that newly added nodes do not ( necessarily ) link to their ambassadors , which in fact produces degree assortativity . since a node copies the links of its ambassadors , linking to them obviously promotes assortativity . however , in the absence of an explicit process introducing assortativity , ( scale - free ) networks are expected to be degree disassortative @xcite . the analysis in section [ sec : experiments ] thus also includes a variant of forest firemodel denoted butterflymodel , where a node links to its ambassadors only with probability @xmath34 ( considered in @xcite ) , as well as a variant of the proposed citationmodel denoted copyingmodel , where a node links to each ambassador @xcite ( for details see figure [ fig : models ] ) . other authors have proposed models very similar to ours @xcite . nevertheless , these either do not adopt the burning process to traverse the network or the model necessarily links the nodes to their ambassadors , which results in degree assortativity . more precisely , the set of the linked nodes is always a subset of the nodes burned ( or vice versa ) . however , in the case of citationmodel , these two sets can intersect arbitrarily , while they can also be disjoint . section [ sec : analysis ] conducts an empirical analysis of citationmodel and several alternatives proposed in the literature ( see section [ sec : model ] ) . next , networks constructed with different models are compared against a larger citation network ( section [ sec : cora ] ) . figure [ fig : comparison ] shows basic statistics of the networks generated with different graph models for parameters @xmath12 and @xmath34 shown ( see section [ sec : model ] ) . most notably , only the proposed citationmodel gives degree disassortative networks measured by the mixing coefficient @xmath35 $ ] @xcite ( see figures [ fig : comparison : p : r ] and [ fig : comparison : q : r ] ) . @xmath36 is simply a pearson correlation coefficient of degrees at links ends . thus , @xmath37 for citationmodel , while @xmath38 for forest fireand butterflymodels . observe that copyingmodel also generates networks with @xmath39 for very large @xmath12 and @xmath34 , however , these are much denser than comparable real - world networks ( see figures [ fig : comparison : p : k ] and [ fig : comparison : q : k ] ) . on the other hand , all models give small - world networks with short mean distance between the nodes @xmath40 @xcite ( see figures [ fig : comparison : p : l ] and [ fig : comparison : q : l ] ) and high transitivity measured by the clustering coefficient @xmath41 $ ] @xcite ( see figures [ fig : comparison : p : c ] and [ fig : comparison : q : c ] ) . note that @xmath42 increases with @xmath12 , while @xmath34 has little effect on @xmath42 . furthermore , all models generate networks with clear community structure according to modularity @xmath43 $ ] @xcite , where @xmath44 is estimated using a fast multi - stage optimization @xcite ( see figures [ fig : comparison : p : q ] and [ fig : comparison : q : q ] ) . although @xmath44 decreases with increasing @xmath12 or @xmath34 in the case of citationand copyingmodels , the values are somewhat comparable to those observed in real - world networks . forest fireand butterflymodels , however , appear to overestimate @xmath44 for selected @xmath12 and @xmath34 . networks constructed with citationmodel also reveal scale - free degree distributions @xcite ( see figure [ fig : cora : pk ] ) , thus , the model generates most common properties of real - world networks . cccccc model & @xmath12 & @xmath34 & @xmath45 & @xmath10 & @xmath36 + forest fire & @xmath46 & - & @xmath47 & @xmath48 & @xmath49 + citation & @xmath50 & @xmath51 & @xmath52 & @xmath53 & @xmath54 + _ cora _ & & & @xmath55 & @xmath56 & @xmath57 + due to a natural interpretation for citation networks ( see section [ sec : model ] ) , the proposed model has different practical applications in bibliometrics . we here analyze author citation dynamics based on the famous _ cora_dataset @xcite that contains computer science papers collected from the web , and also the references automatically parsed from the bibliographies of the papers . we extract a citation network with @xmath58 , while other statistics are reported in table [ tbl : cora ] . table [ tbl : cora ] also includes the networks generated with citationand forest firemodels , where parameters @xmath12 and @xmath34 were estimated as described in section [ sec : model ] . note that citationmodel well matches the disassortative mixing regime in _ cora_citation network ( observe also a similar trend in figure [ fig : cora : kn ] ) , while forest firemodel gives degree assortative networks . ( for comparison based on other network properties see @xcite . ) recall that @xmath28 in equation ( [ equ : burned ] ) can be seen as the number references actually read by an author of some paper . thus , the fraction of papers considered by the authors , relative to the number of all papers cited , can be estimated to @xmath59 . the value is much larger than expected @xcite , however , the results are largely influenced by an automatic sampling procedure @xcite ( i.e. , on average , only @xmath60 references of each paper are also included in the network ) . the paper proposes a simple graph model that generates networks with most common properties of real - world networks and , in contrast to many other models , dissasortative degree mixing . the model also has a natural interpretation for citation networks with different practical applications . due to simplicity , the analysis in the paper is based on undirected networks . however , this presents a serious limitation , especially for citation networks considered here . future work will extend the analysis to directed and also other types of networks , while more reliable datasets will be used for the analysis of author citation dynamics ( based on _ dblp _ and _ wos _ data ) . furthermore , the model will be rigorously compared against others with similar characteristics @xcite . m. mcglohon , l. akoglu , and c. faloutsos . weighted graphs and disconnected components : patterns and a generator . in _ proceedings of the acm sigkdd international conference on knowledge discovery and data mining _ , page 524532 , new york , ny , usa , 2008 .
complex networks of real - world systems are believed to be controlled by common phenomena , producing structures far from regular or random . these include scale - free degree distributions , small - world structure and assortative mixing by degree , which are also the properties captured by different random graph models proposed in the literature . however , many ( non - social ) real - world networks are in fact disassortative by degree . thus , we here propose a simple evolving model that generates networks with most common properties of real - world networks including degree disassortativity . furthermore , the model has a natural interpretation for citation networks with different practical applications . [ model validation and analysis ]
SECTION 1. SHORT TITLE. This Act may be cited as the ``Servicemembers' Group Life Insurance Enhancement Act of 2005''. SEC. 2. REPEALER. Effective as of August 31, 2005, section 1012 of division A of the Emergency Supplemental Appropriations Act for Defense, the Global War on Terror, and Tsunami Relief, 2005 (Public Law 109-13; 119 Stat. 244), including the amendments made by that section, are repealed, and sections 1967, 1969, 1970, and 1977 of title 38, United States Code, shall be applied as if that section had not been enacted. SEC. 3. INCREASE FROM $250,000 TO $400,000 IN AUTOMATIC MAXIMUM COVERAGE UNDER SERVICEMEMBERS' GROUP LIFE INSURANCE AND VETERANS' GROUP LIFE INSURANCE. (a) Maximum Under SGLI.--Section 1967 of title 38, United States Code, is amended-- (1) in subsection (a)(3)(A)(i), by striking ``$250,000'' and inserting ``$400,000''; and (2) in subsection (d), by striking ``of $250,000'' and inserting ``in effect under paragraph (3)(A)(i) of that subsection''. (b) Maximum Under VGLI.--Section 1977(a) of such title is amended-- (1) in paragraph (1), by striking ``in excess of $250,000 at any one time'' and inserting ``at any one time in excess of the maximum amount for Servicemembers' Group Life Insurance in effect under section 1967(a)(3)(A)(i) of this title''; and (2) in paragraph (2)-- (A) by striking ``for less than $250,000 under Servicemembers' Group Life Insurance'' and inserting ``under Servicemembers' Group Life Insurance for less than the maximum amount for such insurance in effect under section 1967(a)(3)(A)(i) of this title''; and (B) by striking ``does not exceed $250,000'' and inserting ``does not exceed such maximum amount in effect under such section''. (c) Effective Date.--The amendments made by this section shall take effect as of September 1, 2005, and shall apply with respect to deaths occurring on or after that date. SEC. 4. SPOUSAL NOTIFICATIONS RELATING TO SERVICEMEMBERS' GROUP LIFE INSURANCE PROGRAM. Effective as of September 1, 2005, section 1967 of title 38, United States Code, is amended by adding at the end the following new subsection: ``(f)(1) If a member who is married and who is eligible for insurance under this section makes an election under subsection (a)(2)(A) not to be insured under this subchapter, the Secretary concerned shall notify the member's spouse, in writing, of that election. ``(2) In the case of a member who is married and who is insured under this section and whose spouse is designated as a beneficiary of the member under this subchapter, whenever the member makes an election under subsection (a)(3)(B) for insurance of the member in an amount that is less than the maximum amount provided under subsection (a)(3)(A)(i), the Secretary concerned shall notify the member's spouse, in writing, of that election-- ``(A) in the case of the first such election; and ``(B) in the case of any subsequent such election if the effect of such election is to reduce the amount of insurance coverage of the member from that in effect immediately before such election. ``(3) In the case of a member who is married and who is insured under this section, if the member makes a designation under section 1970(a) of this title of any person other than the spouse or a child of the member as the beneficiary of the member for any amount of insurance under this subchapter, the Secretary concerned shall notify the member's spouse, in writing, that such a beneficiary designation has been made by the member, except that such a notification is not required if the spouse has previously received such a notification under this paragraph and if immediately before the new designation by the member under section 1970(a) of this title the spouse is not a designated beneficiary of the member for any amount of insurance under this subchapter. ``(4) A notification required by this subsection is satisfied by a good faith effort to provide the required information to the spouse at the last address of the spouse in the records of the Secretary concerned. Failure to provide a notification required under this subsection in a timely manner does not affect the validity of any election specified in paragraph (1) or (2) or beneficiary designation specified in paragraph (3).''. SEC. 5. INCREMENTS OF INSURANCE THAT MAY BE ELECTED. (a) Increase in Increment Amount.--Subsection (a)(3)(B) of section 1967 of title 38, United States Code, is amended by striking ``member or spouse'' in the last sentence and inserting ``member, be evenly divisible by $50,000 and, in the case of a member's spouse,''. (b) Effective Date.--The amendment made by subsection (a) shall take effect as of September 1, 2005. Speaker of the House of Representatives. Vice President of the United States and President of the Senate.
Servicemembers' Group Life Insurance Enhancement Act of 2005 - Repeals, as of August 31, 2005, section 1012 of Division A of P.L. 109-13 which increased the maximum amount of coverage under the Servicemembers' Group Life Insurance (SGLI) program to $400,000 and, for members serving in certain areas or operations, allowed $150,000 of such amount to be paid for by the Secretary concerned. Reinstates Federal provisions concerning such coverage as in effect prior to the enactment of the above Act. Reinstates the PL 109-13 SGLI $400,000 maximum member coverage amount.Requires the Secretary of the military department concerned to notify a member's spouse when a member who is married and is: (1) eligible for SGLI elects not to be so insured; (2) insured and whose spouse is designated as a beneficiary if the member elects coverage in an amount less than the maximum; or (3) insured makes a beneficiary designation of a person other than the member's spouse or child. Requires amounts of SGLI elected by members to be evenly divisible by $50,000 (currently $10,000).
radiation - induced aneurysm is a rare complication for head and neck cancer , and the pathogenesis is not fully understood.1 2 3 4 5 6 7 8 but the mechanism is likely to be similar to that of radiation - induced chronic vascular damage.9 10 11 12 several authors have reported 30 cases of radiation - induced intracranial aneurysms with subsequent rupture.1 2 5 8 13 these aneurysms were diagnosed from 10 months to 21 years after radiation therapy . so far , only seven cases of aneurysm after stereotactic radiosurgery ( srs ) and/or stereotactic radiotherapy ( srt ) have been described.14 15 16 17 18 19 20 all of these patients underwent repeated radiotherapies in various combinations . we present two cases of catastrophic epistaxis due to a ruptured internal carotid artery ( ica ) aneurysm induced by repeated srt for an anterior skull base tumor and successfully treated by endovascular surgery . srt for skull base tumors may be very effective to control these tumors . however , these cases suggest that the development of a radiation - induced aneurysm should be considered a possible serious complication in the case of repeated srt . a 29-year - old man was referred to our institution for the treatment of a large ewing primitive neuroectodermal tumor ( pnet ) that occupied the right orbit and ethmoid and maxillary sinus with right progressive visual loss in four years earlier ( fig . postoperatively , the patient underwent adjuvant chemotherapy and srt with a dose ranging from 45 to 54.9 gy in 15 fractions that produced a complete response . therefore , the second srt was performed with a dose ranging from 53.5 to 62.3 gy in 15 fractions that resulted in the partial response . however , 42 months after surgery , tumor relapse was revealed in the right orbit that remarkably had eroded the sphenoid bone . he underwent the third srt with a dose ranging from 52.8 to 60.0 gy in 15 fractions . magnetic resonance imaging ( mri ) demonstrated the tumor had almost disappeared after srt ( fig . a ) axial t1-weighted magnetic resonance image with gadolinium ( mri - gd ) before the surgery revealed the tumor in the orbit and ethmoid sinus adjacent to the right internal carotid artery ( ica ) . ( b ) axial mri - gd after the third stereotactic radiotherapy demonstrated remarkable shrinkage of the tumor . ( c ) computed tomography scan on emergent admission due to massive epistaxis revealed the hematoma at the middle cranial fossa and pneumocephalus . ( d ) right internal carotid angiogram showed a right petrous ica aneurysm ( arrow ) with slight stenosis of the adjacent ica ( arrowhead ) . ( e ) left internal carotid angiogram after the endovascular treatment revealed the tolerable cross - flow via the anterior communicating artery . the patient was admitted to our hospital with complaints of significant epistaxis with hypovolemic shock 6 months after the final srt . a computed tomography scan revealed a hematoma at the middle cranial fossa and paranasal sinuses , and pneumocephalus ( fig . cerebral angiography showed a right petrous ica aneurysm with slight stenosis of the adjacent ica ( fig . because of rebleeding during the cerebral angiography , we urgently performed endovascular parent - artery occlusion without balloon test occlusion ( bto ) to save his life . cerebral angiography after the endovascular treatment showed complete disappearance of the aneurysm with a tolerable cross - flow via the anterior communicating artery ( acoa ) ( fig . he recovered fully and was discharged 3 weeks after surgery without new neurologic deficits . but 6 months after endovascular treatment , he died from an untreatable tumor relapse . a 61-year - old man was admitted to our hospital for the treatment of a left large sphenocavernous meningioma in 1999 at 48 years of age . the tumor was partially resected via the orbitozygomatic approach without removal of the cavernous mass . the left cavernous tumor had gradually grown 23 months after the initial surgery and was treated by srs using gamma knife . the tumor margin was covered by the 50% isodose line , and 12 gy were delivered to the margin . the left cavernous ica was located within the radiation field . however , the rest of the tumor continued to grow to the infratemporal fossa ( fig . two surgeries , using the infratemporal fossa approach and transsphenoidal approach , were required to remove the extracranial tumor without removal of the cavernous tumor 83 months after the first operation . the following month , the patient underwent srt using cyber knife with a dose ranging from 30.0 to 47.6 gy in five fractions that produced a complete response ( fig . coronal t1-weighted magnetic resonance image with gadolinium ( mri - gd ) after stereotactic radiosurgery revealed tumor recurrence in the cavernous sinus and the left infratemporal fossa surrounding the left internal carotid artery ( ica ) . ( b ) mri - gd after stereotactic radiosurgery and stereotactic radiotherapy demonstrated an almost disappearance of the tumor . ( c ) left internal carotid angiogram demonstrated a small aneurysm at the left cavernous ica ( arrow ) . ( d ) right internal carotid angiogram after the endovascular treatment showed enough collateral flow via the anterior communicating artery . the patient was admitted to our hospital with complaints of massive epistaxis 77 months after the last srt . cerebral angiography showed a small aneurysm located at the cavernous portion of the left ica ( fig . 2c ) . bto of the left ica demonstrated the presence of collateral flow via the acoa without a reduced regional cerebral oxygenation state on the occluded side under the monitoring of near - infrared spectroscopy . cerebral angiography after the endovascular treatment showed complete disappearance of the aneurysm with enough collateral flow via the acoa ( fig . a 29-year - old man was referred to our institution for the treatment of a large ewing primitive neuroectodermal tumor ( pnet ) that occupied the right orbit and ethmoid and maxillary sinus with right progressive visual loss in four years earlier ( fig . postoperatively , the patient underwent adjuvant chemotherapy and srt with a dose ranging from 45 to 54.9 gy in 15 fractions that produced a complete response . therefore , the second srt was performed with a dose ranging from 53.5 to 62.3 gy in 15 fractions that resulted in the partial response . however , 42 months after surgery , tumor relapse was revealed in the right orbit that remarkably had eroded the sphenoid bone . he underwent the third srt with a dose ranging from 52.8 to 60.0 gy in 15 fractions . magnetic resonance imaging ( mri ) demonstrated the tumor had almost disappeared after srt ( fig . a ) axial t1-weighted magnetic resonance image with gadolinium ( mri - gd ) before the surgery revealed the tumor in the orbit and ethmoid sinus adjacent to the right internal carotid artery ( ica ) . ( b ) axial mri - gd after the third stereotactic radiotherapy demonstrated remarkable shrinkage of the tumor . ( c ) computed tomography scan on emergent admission due to massive epistaxis revealed the hematoma at the middle cranial fossa and pneumocephalus . ( d ) right internal carotid angiogram showed a right petrous ica aneurysm ( arrow ) with slight stenosis of the adjacent ica ( arrowhead ) . ( e ) left internal carotid angiogram after the endovascular treatment revealed the tolerable cross - flow via the anterior communicating artery . the patient was admitted to our hospital with complaints of significant epistaxis with hypovolemic shock 6 months after the final srt . a computed tomography scan revealed a hematoma at the middle cranial fossa and paranasal sinuses , and pneumocephalus ( fig . cerebral angiography showed a right petrous ica aneurysm with slight stenosis of the adjacent ica ( fig . because of rebleeding during the cerebral angiography , we urgently performed endovascular parent - artery occlusion without balloon test occlusion ( bto ) to save his life . cerebral angiography after the endovascular treatment showed complete disappearance of the aneurysm with a tolerable cross - flow via the anterior communicating artery ( acoa ) ( fig . he recovered fully and was discharged 3 weeks after surgery without new neurologic deficits . but 6 months after endovascular treatment , he died from an untreatable tumor relapse . a 61-year - old man was admitted to our hospital for the treatment of a left large sphenocavernous meningioma in 1999 at 48 years of age . the tumor was partially resected via the orbitozygomatic approach without removal of the cavernous mass . the left cavernous tumor had gradually grown 23 months after the initial surgery and was treated by srs using gamma knife . the tumor margin was covered by the 50% isodose line , and 12 gy were delivered to the margin . the left cavernous ica was located within the radiation field . however , the rest of the tumor continued to grow to the infratemporal fossa ( fig . two surgeries , using the infratemporal fossa approach and transsphenoidal approach , were required to remove the extracranial tumor without removal of the cavernous tumor 83 months after the first operation . the following month , the patient underwent srt using cyber knife with a dose ranging from 30.0 to 47.6 gy in five fractions that produced a complete response ( fig . ( a ) coronal t1-weighted magnetic resonance image with gadolinium ( mri - gd ) after stereotactic radiosurgery revealed tumor recurrence in the cavernous sinus and the left infratemporal fossa surrounding the left internal carotid artery ( ica ) . ( b ) mri - gd after stereotactic radiosurgery and stereotactic radiotherapy demonstrated an almost disappearance of the tumor . ( c ) left internal carotid angiogram demonstrated a small aneurysm at the left cavernous ica ( arrow ) . ( d ) right internal carotid angiogram after the endovascular treatment showed enough collateral flow via the anterior communicating artery . the patient was admitted to our hospital with complaints of massive epistaxis 77 months after the last srt . cerebral angiography showed a small aneurysm located at the cavernous portion of the left ica ( fig . 2c ) . bto of the left ica demonstrated the presence of collateral flow via the acoa without a reduced regional cerebral oxygenation state on the occluded side under the monitoring of near - infrared spectroscopy . cerebral angiography after the endovascular treatment showed complete disappearance of the aneurysm with enough collateral flow via the acoa ( fig . radiation - induced carotid artery aneurysm is a rare complication of radiation therapy for head and neck carcinoma , but it is a life - threatening situation . the pathogenesis of radiation - induced aneurysm remains speculative.1 2 3 4 5 6 7 8 however the mechanism is likely to be similar to that of radiation - induced vasculopathy , due to chronic vascular damage such as obstruction of the vasa vasorum , premature atherosclerosis , adventitial fibrosis , and necrosis of the arterial wall.9 10 11 12 combined with high blood pressure of the great vessel , it could result in the rupture of the arterial wall and even dissection with extravasation blood.13 22 23 therefore , even a small radiation - induced aneurysm is more prone to rupture than other common saccular aneurysms.24 the clinical characteristics of radiation - induced aneurysms differ from other saccular aneurysms.13 radiation - induced aneurysms originate directly from the arterial wall , which is less likely to be influenced by the direction of the blood flow , in contrast to other saccular aneurysms . therefore , the formation of an aneurysm after irradiation might occur at any location on the vessel included within the radiation fields . in our cases , these aneurysms were not located at a branching site and were included within the radiation field . these findings suggest that the srt was responsible for the formation of the carotid artery aneurysm . several authors have reported 30 cases of radiation - induced intracranial aneurysms with subsequent rupture.1 2 5 8 13 these aneurysms were diagnosed from 10 months to 21 years after radiation therapy . however , our literature review yielded only seven cases of aneurysm induced by srs and/or srt.14 15 16 17 18 19 20 among them , four cases were presented as anterior inferior cerebellar artery aneurysm induced by srs ( gamma knife ) for vestibular schwannoma.14 18 19 20 the remaining three cases were reported as ica aneurysms15 16 17 ( table 1 ) . with the inclusion of our cases , these patients were three men and two women ( mean age : 52.2 years ; range : 2962 years ) . there were two cases of nasopharyngeal carcinoma , and one each of pituitary adenoma , atypical meningioma , and ewing pnet . although the interval between the latest radiotherapy and the diagnosis of the aneurysm varied from 3 months to 13 years ( mean : 49.8 months ) , three cases developed within a year . these results indicated that repeated srt causes an aneurysm to occur earlier than conventional radiotherapy or single srt . abbreviations : 3d - crt , three - dimensional conformal radiotherapy ; ec - ic bypass , external carotid - internal carotid artery bypass ; ica , internal carotid artery ; pnet , primitive neuroectodermal tumor ; rt , radiotherapy ; sah , subarachnoid hemorrhage ; srs , stereotactic radiosurgery ; srt , stereotactic radiotherapy . srt makes it possible to deliver efficacious therapeutic doses accurately to the targeted lesion with secure preservation of adjacent normal anatomical structures . however , if these structures are located within the targeted lesion , they must be involved in the radiation field . therefore the surviving patients who have received srt should undergo sequential follow - up for possible vascular involvement . treatment for radiation - induced aneurysms includes clipping,2 3 5 24 25 26 trapping,11 27 and wrapping the aneurysm and parent artery.2 5 28 29 in addition , parent artery occlusion using an endovascular technique is effective.19 28 30 because of the high risk of mortality , if the radiation - induced aneurysm ruptures , aggressive surgical intervention or endovascular treatment should be considered for the aneurysm . sacrifice of the carotid artery would lead to severe cerebrovascular events , and therefore a bto should be performed . if a bto is successful , trapping or parent artery occlusion becomes an option . if the patient can not tolerate the test , an extracranial - to - intracranial bypass surgery should be considered . in case 1 of our series , the patient was semicomatose and in a state of hypovolemic shock due to repeated massive epistaxis . therefore , an immediate salvage procedure was needed to save his life without performing bto . in case 2 we have presented two cases of a ruptured ica aneurysm induced by repeated srt for anterior skull base tumor . it was definitely difficult to clarify accurately the timing of aneurysm formation in our cases . in addition , although the primary factor was presumed the high dose delivered to the ica by the repeated srt , an unrecognized carotid injury at the former surgical intervention to the tumor or direct damage to the vessel wall by the tumor could also have been the probable causes . there are some reports on iatrogenic intracranial traumatic aneurysms after the resection of skull base tumors.31 32 33 it was suggested that most traumatic intracranial aneurysms have a symptomatic onset within 4 weeks after injury of the vessel wall.32 in our cases , however , the hemorrhagic presentation appeared 48 and 78 months after the final surgery , respectively . therefore , we are convinced that the aneurysms in our cases were most likely induced by the repeated srt and indicated a low probability of traumatic origin . histologic analysis , if possible , might contribute to an understanding of the entity of these lesions . we present two cases of catastrophic epistaxis due to ica aneurysm that were most likely induced by repeated srt for anterior skull base tumors . the srt may be very effective to control the residual tumor as well as tumor relapse . however , the possible development of radiation - induced aneurysm of the carotid artery should be considered in the case of repeated srt for malignant skull base tumors .
objectives radiation - induced aneurysm is a rare complication for head and neck tumors . only seven cases of an aneurysm after stereotactic radiosurgery and/or stereotactic radiotherapy ( srt ) have been described . we report two patients with a ruptured internal carotid artery ( ica ) aneurysm presenting with catastrophic epistaxis after repeated srt for an anterior skull base tumor . results two male patients received repeated srt in various combinations following surgery for an anterior skull base tumor . they presented with significant epistaxis due to rupture of the aneurysm of the ica 6 and 77 months after the final srt , respectively . the aneurysms were located within the radiation field . preoperative angiography had revealed no aneurysms . thus the aneurysms in these cases were most likely induced by the repeated srt . conclusions this is a proven report of aneurysm formation following repeated srt without conventional radiotherapy . srt may be very effective to control malignant skull base tumors . however , the possible development of radiation - induced aneurysm of the ica should be considered in the case of repeated srt . the surviving patients who have received srt should undergo sequential follow - up for possible vascular involvement .
SECTION 1. SHORT TITLE. This Act may be cited as the ``Medicare Medication Evaluation and Dispensing System Act of 1995''. SEC. 2. ESTABLISHMENT OF MEDICATION EVALUATION AND DISPENSING SYSTEM UNDER MEDICARE. (a) In General.--Title XVIII of the Social Security Act (42 U.S.C. 1395 et seq.) is amended by inserting after section 1888 the following new section: ``medicare medication evaluation and dispensing system ``Sec. 1889. (a) Establishment.-- ``(1) In general.--In accordance with the requirements of this section, the Secretary shall establish and operate the Medicare Medication Evaluation and Dispensing System (hereafter in this section referred to as the `MMEDS') to provide for-- ``(A) prospective and retrospective review of prescription drugs furnished to Medicare beneficiaries (in accordance with subsection (b)); ``(B) educating physicians, patients, and pharmacists regarding the appropriate use of prescription drugs (in accordance with subsection (c)); and ``(C) the establishment of standards for counseling Medicare beneficiaries (consistent with the laws of the State in which a beneficiary resides) regarding the appropriate use of prescription drugs. ``(2) Treatment of drugs not covered under medicare.--The MMEDS shall provide for review, information, and counseling with respect to any prescription drug furnished to a Medicare beneficiary without regard to whether or not payment may be made for the drug under this title. ``(3) Medicare beneficiary defined.--In this section, a `Medicare beneficiary' is any individual entitled to benefits under part A or enrolled under part B. ``(b) Requirements for Review of Prescriptions.-- ``(1) In general.--The MMEDS shall provide on-line prospective review of prescriptions on a 24-hour basis and periodic retrospective review of claims. ``(2) Prospective drug utilization review.-- ``(A) In general.--The MMEDS shall provide for on- line prospective review of each outpatient prescription drug prescribed for a Medicare beneficiary before the prescription is filled or the drug is furnished, including screening for potential drug therapy problems due to therapeutic duplication, drug-to-drug interactions, drug-disease contraindications, and incorrect drug dosage or duration of drug treatment. ``(B) Discussion of appropriate use.--In conducting prospective review under the MMEDS, any individual or entity that dispenses an outpatient prescription drug shall offer (consistent with the law of the State in which the patient resides) to discuss with the patient to whom the drug is furnished or the patient's caregiver (in person if practicable, or through access to a toll-free telephone service) information regarding the appropriate use of the drug, potential interactions between the drug and other drugs dispensed to the individual, and such other matters as the Secretary may require. ``(C) Additional duties.--In carrying out this paragraph, the Secretary shall-- ``(i) develop public domain software which could be used by carriers and pharmacies to provide the on-line prospective review; and ``(ii) study the feasibility and desirability of requiring patient diagnosis codes on prescriptions and the feasibility of expanding the prospective drug utilization review program to include the identification of drug-disease contraindications, interactions with over-the-counter drugs, and drug-allergy interactions. ``(3) Retrospective drug utilization review.--As part of the MMEDS, the Secretary shall provide for a retrospective drug utilization review program to provide for the ongoing periodic examination of claims data and other records on outpatient prescription drugs furnished to Medicare beneficiaries in order to identify patterns of inappropriate or medically unnecessary patient care. ``(4) Use of electronic system.-- ``(A) In general.--As part of the MMEDS, the Secretary shall establish, by not later than June 1, 1997, a point-of-sale electronic system for use by carriers and pharmacies in the submission of information respecting outpatient prescription drugs dispensed to Medicare beneficiaries. Such system shall be consistent with the standards established by the National Council of Prescription Drug Programs. ``(B) Technical assistance.--The Secretary shall provide technical assistance in the use of the electronic system established under subparagraph (A) to carriers and pharmacies. ``(c) Education Regarding Appropriate Use of Prescription Drugs.-- ``(1) In general.--Under the MMEDS, the Secretary (either directly or through contract) shall provide for an educational outreach program to educate patients, pharmacists, and other health care providers concerning-- ``(A) instances or patterns of unnecessary or inappropriate prescribing or dispensing practices for outpatient prescription drugs, ``(B) instances or patterns of substandard care with respect to such drugs, ``(C) potential adverse reactions and interactions, and ``(D) appropriate use of generic products. ``(2) Information on changes in prescribing and dispensing practices.--Under the program described in paragraph (1), the Secretary shall provide information (in such format as the Secretary considers appropriate) on changes in prescribing and dispensing practices to promote the appropriate use of prescription drugs. ``(d) Privacy Protection.--The Secretary shall establish standards to protect from public disclosure any information provided by or through the MMEDS that identifies an individual and relates to the individual's physical or mental health and the identity of any individual (whether a patient or an individual involved in the prescribing, dispensing, or administration of the drug) who is the subject of such information. ``(e) Assistance for Participating Pharmacists.-- ``(1) In general.--The Secretary shall provide to each pharmacist meeting the requirements of paragraph (2)-- ``(A) a distinctive emblem (suitable for display to the public) indicating that the pharmacy participates in the MMEDS, and ``(B) upon request, such technical assistance as the Secretary determines may be necessary for the pharmacist to submit information to and retrieve information from the electronic system established under subsection (b)(4). ``(2) Requirements described.--A pharmacist meets the requirements of this paragraph if the pharmacist is legally authorized under State law (or the State regulatory mechanism provided by State law) of the State in which the drug is received by the beneficiary to dispense outpatient prescription drugs and meets other participation standards established by the Secretary with respect to the following: ``(A) Maintenance of patient records. ``(B) Accuracy of information submitted under the MMEDS. ``(C) Patient counseling. ``(D) Performance of drug use review activities under the MMEDS. ``(f) Adoption of Medicaid Programs.--To the extent considered appropriate by the Secretary, the MMEDS with respect to drugs furnished in a State may include elements applicable to the furnishing of covered outpatient drugs under the State Medicaid program under section 1927.''. (b) Recommendations on Coordination With Programs Under Other Plans.--Not later than October 1, 1996, the Secretary of Health and Human Services shall submit recommendations to Congress on measures-- (1) to ensure the coordination of information collected and disseminated under the Medicare Medication Evaluation and Dispensing System established under section 1889 of the Social Security Act (as added by subsection (a)) with information provided to and collected from similar programs providing services to Medicare beneficiaries enrolled in health care plans (including plans of an organization described in section 1833(a)(1)(A) of such Act or an eligible organization with an agreement in effect under section 1876 of such Act, plans serving as primary plans section 1862(b) of such Act, and medicare supplemental policies described in section 1882 of such Act); and (2) to avoid the duplication of services provided under such System with services provided under such similar programs. (c) Special Rules for Carriers.-- (1) Use of regional carriers.--Section 1842(b)(2) of the Social Security Act (42 U.S.C. 1395u(b)(2)) is amended by adding at the end the following new subparagraph: ``(E) With respect to activities related to the Medicare Medication Evaluation and Dispensing System under section 1889, the Secretary may enter into contracts with carriers under this section to perform the activities on a regional basis.''. (2) Additional functions.--Section 1842(b)(3) of such Act (42 U.S.C. 1395u(b)(3)) is amended-- (A) by striking ``and'' at the end of subparagraph (I); and (B) by inserting after subparagraph (I) the following new subparagraphs: ``(J) if it makes determinations with respect to outpatient prescription drugs which are subject to the Medicare Medication Evaluation and Dispensing System under section 1889, will receive information transmitted under the electronic system established under section 1889(b)(4); ``(K) will enter into such contracts with organizations described in subsection (f)(3) as the Secretary determines may be necessary to implement and operate (and for related functions with respect to) the electronic system established under section 1889(b)(4); and''. (3) Payment on other than a cost basis.--Section 1842(c)(1)(A) of such Act (42 U.S.C. 1395u(c)(1)(A)) is amended-- (A) by inserting ``(A)'' after ``(c)(1)'', (B) in the first sentence, by inserting ``, except as otherwise provided in subparagraph (B),'' after ``under this part, and'', and (C) by adding at the end the following: ``(B) To the extent that a contract under this section provides for activities related to the Medicare Medication Evaluation and Dispensing System under section 1889, the Secretary may provide for payment for those activities based on any method of payment determined by the Secretary to be appropriate.''. (4) Use of other entities.--Section 1842(f) of such Act (42 U.S.C. 1395u(f)) is amended-- (A) by striking ``and'' at the end of paragraph (1), (B) by striking the period at the end of paragraph (2) and inserting ``; and'', and (C) by adding at the end the following: ``(3) with respect to activities related to the Medicare Medication Evaluation and Dispensing System under section 1889, any other private entity which the Secretary determines is qualified to conduct such activities.''. SEC. 3. RECOMMENDATIONS ON MEDICARE COVERAGE OF PHARMACIST PROFESSIONAL SERVICES. Not later than the expiration of the 2-year period which begins on the date of the initial operation of the Medicare Medication Evaluation and Dispensing System under section 1889 of the Social Security Act (as added by section 2(a)), the Secretary of Health and Human Services shall submit to Congress (in consultation with actively practicing pharmacists)-- (1) an analysis of the effect on net aggregate expenditures under the Medicare program from the establishment and operation of such System; and (2) such recommendations as the Secretary considers appropriate regarding the coverage of and payment for pharmacist professional services under part B of the medicare program as the Secretary considers appropriate, except that the Secretary may recommend coverage of and payment for such services only under a methodology which does not result in an increase in net expenditures under the program (taking into account reductions in expenditures under the program as a result of demonstrable reductions in the inappropriate use of outpatient prescription drugs). SEC. 4. DISTRIBUTION OF CONSUMER GUIDE TO OUTPATIENT PRESCRIPTION DRUGS. Not later than January 1, 1997, the Secretary of Health and Human Services shall publish and disseminate a consumer guide to outpatient prescription drugs to assist medicare beneficiaries in reducing expenditures for outpatient prescription drugs and to assist individuals and entities furnishing items and services to such beneficiaries in determining the cost-effectiveness of such drugs.
Medicare Medication Evaluation and Dispensing System Act of 1995 - Amends title XVIII (Medicare) of the Social Security Act to require the Secretary of Health and Human Services to establish and operate the Medicare Medication Evaluation and Dispensing System to provide for: (1) prospective and retrospective review of prescription drugs furnished to Medicare beneficiaries; (2) education of physicians, patients, and pharmacists in the appropriate use of prescription drugs; (3) the establishment of standards for counseling Medicare beneficiaries regarding the appropriate use of prescription drugs; and (4) review, information, and counseling with respect to any prescription drug furnished to a Medicare beneficiary without regard to whether or not payment may be made for the drug under Medicare. Sets forth requirements for review of prescriptions. Requires the Secretary to report to the Congress: (1) an analysis of the effect on net aggregate Medicare expenditures from the establishment of such a System; and (2) any recommendations on Medicare coverage of pharmacist professional services. Directs the Secretary to publish and disseminate a consumer guide to outpatient prescription drugs to assist: (1) Medicare beneficiaries in reducing expenditures for them; and (2) individuals and entities furnishing items and services to such beneficiaries in determining the cost-effectiveness of such drugs.
let @xmath6 be the group of orientation preserving isometries of the hyperbolic space @xmath7 and @xmath8 a torsion - free non - elementary ( = not virtually abelian ) discrete subgroup . the action of @xmath0 extends to @xmath9 where @xmath2 denotes the geometric boundary of @xmath7 , and we define the limit set @xmath10 as the set of accumulation points of a @xmath0-orbit in @xmath11 . if we denote by @xmath12 the critical exponent of @xmath0 , then there exists a @xmath0-invariant conformal density @xmath13 of dimension @xmath12 on @xmath10 by patterson @xcite for @xmath14 and sullivan @xcite for @xmath15 general . we consider the bowen - margulis - sullivan measure @xmath16 on the unit tangent bundle @xmath17 associated to the density @xmath18 ( def . [ def : bms ] ) . when the total mass @xmath19 finite , the geodesic flow is ergodic on @xmath20 @xcite . for a subset @xmath21 and @xmath22 , we denote by @xmath23 the set of all points lying in geodesics emanating from @xmath24 toward @xmath25 , and by @xmath26 the hyperbolic ball of radius @xmath27 centered at @xmath24 . our main theorem is the following : [ thm : main ] suppose that the total mass @xmath28 is finite . let @xmath29 and @xmath30 be borel subsets of @xmath2 whose boundaries are of zero patterson - sullivan measure . then , for any @xmath31 and @xmath32 , as @xmath33 , @xmath34 if @xmath0 is geometrically finite , that is , if the unit neighborhood of the convex core is defined to be the minimal convex set which contains all geodesics connecting any two points in @xmath35 . ] @xmath36 has finite volume , then @xmath37 @xcite . however the above theorem is not restricted only to those groups as there are geometrically infinite groups with @xmath37 ( see @xcite ) . we remark that the assumption of @xmath37 implies that the conformal density @xmath18 is determined uniquely up to homothety ( see ( * ? ? ? * coro.1.8 ) ) . on @xmath38,width=340 ] when @xmath39 , the above counting problem is simply the non - euclidean lattice point counting problem , and was solved by lax and phillips @xcite for geometrically finite groups with @xmath40 . theorem [ thm : main ] for @xmath41 is due to roblin @xcite . when @xmath0 is a lattice , the same type of orbital counting result for @xmath41 was obtained in a much more general setting of riemannian symmetric spaces ( see @xcite , @xcite , @xcite , @xcite , etc . ) . theorem [ thm : main ] for general @xmath42 was proved in @xcite for all lattices in semisimple lie groups ( see also @xcite for the case when @xmath43 ) . we highlight theorem [ thm : main ] for the mbius transformation action of @xmath44 , that is , the action on the extended complex plane @xmath45 by @xmath46 where @xmath47 with @xmath48 and @xmath49 . in the upper half - space model @xmath50 of the hyperbolic @xmath51-space with the metric @xmath52 , the mbius transformations by elements of @xmath44 give rise to all orientation preserving isometries of @xmath53 . for @xmath54 , we have @xmath55 where @xmath56 . hence the following follows from theorem [ thm : main ] : [ thm : motivation ] let @xmath57 be a non - elementary geometrically finite discrete subgroup . for any borel subset @xmath58 of @xmath59 with @xmath60 , we have , as @xmath33 , @xmath61 a similar result holds for the linear fractional transformation action of non - virtually cyclic and finitely generated subgroups of @xmath62 on @xmath63 . after the submission , we were pointed out by the referee that in f. maucourant s thesis @xcite , theorem [ thm : main ] was already proved in the case when the sector is taken to be the whole ball ( i.e. , @xmath64 ) and that his approach which elegantly uses a theorem of roblin ( * ? ? ? * theorem 4.11 ) can be extended to obtain theorem [ mmmm ] of the appendix . as maucourant s result is not published , maucourant agreed to write an appendix on his result . our approach is different from his , as we do not rely on the aforementioned theorem of roblin but on a recent result of oh and shah ( see theorem [ thm : ohshah ] ) . in section 2 , we obtain the main ergodic theorem which is the equidistribution of solvable flows ( theorem [ thm:6.1 ] ) which is of independent interest . in section 3 , we relate the counting function in theorem [ thm : main ] with an average over a solvable flow of a certain function on @xmath65 ( lemma [ lem : thicken1 ] ) and then apply the results in section 2 to conclude theorem [ thm : main ] . some computations such as lemma [ aux ] are a bit tricky due to the fact that the burger - roblin measure @xmath66 is not an invariant measure in general . this approach of establishing the equidistribution of @xmath0-orbits on the boundary via the study of solvable flows on @xmath65 was first used in @xcite . * acknowledgment : * we thank thomas roblin for useful comments . for @xmath67 and @xmath32 , the _ busemann function _ @xmath68 is defined as follows : @xmath69 where @xmath70 is a geodesic ray toward @xmath71 . for a unit tangent vector @xmath72 , we denote by @xmath73 the base point of @xmath74 and by @xmath75 ( resp . @xmath76 ) the forward ( resp . backward ) endpoint of the geodesic determined by @xmath74 . let @xmath0 be a non - elementary discrete subgroup of @xmath77 . let @xmath78 denote a patterson - sullivan density for @xmath0 , i.e. , each @xmath79 is a finite measure supported on @xmath3 satisfying : for any @xmath80 , @xmath81 and @xmath82 , @xmath83 where @xmath84 . [ def : bms ] the _ bowen - margulis - sullivan measure _ @xmath85 associated to @xmath18 ( @xcite , @xcite , @xcite ) is defined as the measure induced on @xmath65 of the following @xmath0-invariant measure @xmath86 on @xmath87 : @xmath88 we denote by @xmath89 a @xmath6-invariant conformal density of dimension @xmath90 , which is unique up to homothety . the _ burger - roblin measure _ @xmath91 associated to @xmath18 and @xmath92 ( @xcite , @xcite ) is defined as the measure induced on @xmath93 of the following @xmath0-invariant measure @xmath94 on @xmath87 : @xmath95 the measure @xmath94 is supported on the set of unit tangent vectors @xmath74 such that @xmath76 belongs to the limit set @xmath96 . we fix @xmath97 and @xmath32 in the rest of this section . let @xmath98 be the stabilizer of @xmath24 in @xmath6 and @xmath99 denote the stabilizer of @xmath32 . the subgroup @xmath99 is a minimal parabolic subgroup of @xmath6 and is the normalizer of its unipotent radical @xmath100 . without loss of generality , we may assume that @xmath101 is the probability measure . denote by @xmath102 the unit vector based at @xmath24 such that @xmath103 . we set @xmath104 setting @xmath105 we have ( cf . 4.1 ) ) * @xmath106 where @xmath107 ; * @xmath108 where @xmath109 is the centralizer of @xmath110 in @xmath98 and @xmath111 ; * @xmath100 is the expanding horospherical subgroup of @xmath6 with respect to @xmath112 , i.e. , @xmath113 . the above cartan decomposition @xmath106 says that for any @xmath114 , there exists a unique element @xmath115 such that @xmath116 , for @xmath117 . moreover , @xmath118 implies that @xmath119 and @xmath120 for some @xmath121 . we may identify @xmath122 with @xmath7 where @xmath123 corresponds to @xmath124 and @xmath125 with @xmath126 where @xmath127 corresponds to @xmath128 . let @xmath129 be the maximal split solvable subgroup of @xmath6 given by @xmath130 for @xmath131 and a subset @xmath132 with @xmath133 , set @xmath134 where @xmath135 . our aim in this section is to prove an equidistribution of @xmath136 on @xmath65 : theorem [ thm:6.1 ] . the following is the main ergodic ingredient we use . @xcite[thm : ohshah ] suppose that @xmath137 . let @xmath58 be a borel subset of @xmath98 with @xmath138 and with @xmath139 . for any @xmath140 , @xmath141 by the iwasawa decomposition @xmath142 , the map @xmath143 is a diffeomorphism , say , @xmath144 . let @xmath145 be the contracting horospherical subgroup of @xmath6 with respect to @xmath112 : @xmath146 . the map @xmath147 , @xmath148 , composed with @xmath149 , is an @xmath109-equivariant map @xmath150 which is a diffeomorphism onto its image , which is a zariski open subset . let @xmath151 be the image of @xmath152 under this map . we note that the complement of @xmath153 in @xmath154 is a point . [ go ] let @xmath155 . if @xmath156 is a neighborhood of @xmath157 and @xmath158 is a compact subset of @xmath151 , there exists @xmath159 such that for any @xmath121 , @xmath160 since @xmath161 , the conjugation by @xmath162 expands @xmath163 by the factor of @xmath164 , and hence we can find @xmath165 such that @xmath166 for all @xmath167 . hence @xmath168 as @xmath169 . by the uniqueness of the decomposition @xmath170 , we have the desired inclusion . we denote by @xmath171 the haar measure on @xmath6 such that for @xmath172 , @xmath173 where @xmath174 denotes the probability haar measure on @xmath98 . we denote by @xmath175 the left - invariant haar measure on @xmath129 given by the relation : @xmath176 where @xmath177 . in the rest of this section , we assume that @xmath137 . the following lemma is a special case of ( * ? ? ? 3.1 ) : [ rud ] any sphere centered at @xmath178 has measure zero with respect to @xmath79 . [ prop:6.6 ] let @xmath179 be an open neighborhood of @xmath180 in @xmath98 such that @xmath181 . let @xmath58 be a borel subset of @xmath98 with @xmath138 and with @xmath139 . then for any @xmath182 , @xmath183 as @xmath184 where @xmath185 and @xmath186 . note that @xmath187 where @xmath188 . setting @xmath189 , we have @xmath190 set for @xmath121 , @xmath191 where @xmath151 is the image of @xmath145 in @xmath98 . we note that since @xmath192 is an open zariski dense subset whose complement is a point and @xmath79 is atom free , @xmath193 and @xmath194 . write @xmath195 for @xmath196 . let @xmath197 with @xmath198 . by lemma [ rud ] , for any fixed @xmath199 , we can take a compact subset @xmath200 such that @xmath201 and @xmath202 . if we set @xmath203 , then @xmath204 and @xmath205 since @xmath206 . by lemma [ go ] , there exists @xmath207 such that for all @xmath208 , @xmath209 on the other hand , as @xmath169 , @xmath210 without loss of generality we assume below that @xmath211 is non - negative . hence for all @xmath208 , @xmath212 note that by applying theorem [ thm : ohshah ] @xmath213 where @xmath214 . hence @xmath215 and similarly @xmath216 as @xmath199 is arbitrary and @xmath217 , we deduce @xmath218 using that @xmath219 , we obtain that for any @xmath220 , as @xmath221 , @xmath222 now for @xmath223 , we claim that @xmath224 consider the set @xmath225 as @xmath226 , we have by the previous case that @xmath227 since @xmath228 and @xmath229 the claim follows . since the image of @xmath151 is an open zariski dense subset of @xmath154 , we may replace @xmath98 by @xmath230 in the integration over @xmath98 and hence @xmath231 this completes the proof of proposition [ prop:6.6 ] . [ thm:6.1 ] let @xmath58 be a borel subset of @xmath232 with @xmath233 . then for any @xmath234 , as @xmath33 , @xmath235 let @xmath236 be an @xmath237-neighborhood of @xmath180 in @xmath98 such that @xmath238 . for any @xmath239 and @xmath199 , define functions @xmath240 as follows : @xmath241 let @xmath242 . by the uniform continuity of @xmath211 and the @xmath109-invariance , there exists @xmath243 such that @xmath244 for all @xmath245 . without loss of generality we may assume @xmath246 . note that , by applying proposition [ prop:6.6 ] , @xmath247 similarly @xmath248 since @xmath249 we deduce that @xmath250 and @xmath251 as @xmath242 is arbitrary , this proves the claim . fix @xmath97 and @xmath252 . we keep the same notation from the previous section . let @xmath253 and choose @xmath254 such that @xmath255 . for a subset @xmath256 of @xmath6 , we denote by @xmath257 the conjugate @xmath258 . note that @xmath259 is the stabilizer of @xmath260 and that @xmath261 stabilizes @xmath262 . for @xmath263 , we set @xmath264 so that @xmath265 and @xmath266 . we assume that the boundaries of @xmath267 have measure zero with respect to the patterson - sullivan density . in this notation , we have @xmath268 and hence the condition @xmath269 becomes @xmath270 . and @xmath271 is equivalent to @xmath272 and hence to @xmath273 . for @xmath245 , we write @xmath274 where @xmath275 and @xmath276 are uniquely determined . hence setting @xmath277 the number we want to count is the following : @xmath278 let @xmath236 be an @xmath237-neighborhood of @xmath180 in @xmath98 such that @xmath279 . for the @xmath237-neighborhood @xmath280 of @xmath180 in @xmath110 , by the strong wavefront lemma ( see @xcite or @xcite ) there exists a symmetric neighborhood @xmath281 of @xmath180 in @xmath6 and @xmath165 such that for all @xmath282 and all @xmath167 , @xmath283 choose a symmetric neighborhood @xmath284 so that @xmath285 where @xmath286 and @xmath287 . we may assume without loss of generality that @xmath288 satisfies @xmath289 for all @xmath290 . we set @xmath291 and note that @xmath292 . . then there exists @xmath293 such that for all @xmath294 , @xmath295 where @xmath296 and @xmath297 . this is possible since the boundary of @xmath298 has measure zero with respect to @xmath79 . similarly , we may assume that @xmath299 where @xmath300 and @xmath301 where @xmath302 . we also set @xmath303 . we choose @xmath304 such that @xmath305 , @xmath306 for @xmath307 , @xmath308 for @xmath309 , @xmath310 for @xmath311 , and @xmath312 for @xmath313 . we denote by @xmath314 the left invariant haar measure on @xmath315 given by : for @xmath316 , @xmath317 choosing a non - negative function @xmath318 supported on @xmath319 and with @xmath320 , we define a function @xmath321 on @xmath322 by @xmath323 where @xmath324 with @xmath325 and @xmath276 uniquely determined and @xmath243 . define @xmath326 which is an integrable function defined on @xmath327 . we set @xmath328 @xmath329 @xmath330 where @xmath331 and @xmath332 . when @xmath333 , we simply omit the superscript @xmath334 from the above notation . note that @xmath335 [ lem : thicken1 ] let @xmath165 be taken so that holds . for any @xmath336 and small @xmath242 , we have 1 . @xmath337 2 . @xmath338 where @xmath339 and @xmath340 and @xmath243 . for simplicity , we set @xmath341 and @xmath342 . we have @xmath343 since @xmath314 is left - invariant . since we have chosen @xmath344 so that @xmath345 for any @xmath346 such that @xmath347 , @xmath348 and hence @xmath349 it follows that @xmath350 similarly , we have @xmath351 since @xmath352 , we have @xmath353 therefore for @xmath346 such that @xmath354 , we have @xmath355 hence it follows that @xmath356 [ r ] let @xmath282 and @xmath357 . writing @xmath358 , we have @xmath359 since @xmath360 , we compute that @xmath361 for simplicity , we set @xmath362 and @xmath363 . [ aux ] we have @xmath364 we use the formula for @xmath365 : for any @xmath366 , @xmath367 define functions @xmath368 on @xmath6 : for @xmath369 , @xmath370 note that @xmath371 and hence @xmath372 we then have @xmath373 for @xmath245 , define @xmath374 to be the unique element such that @xmath375 we note that @xmath376 hence together with lemma [ r ] , @xmath377 define functions @xmath378 by @xmath379 note that @xmath380 vanishes outside @xmath381 and is @xmath382 on @xmath383 . therefore , using the conformal property of @xmath13 : @xmath384 we have @xmath385 since @xmath386 and @xmath129 stabilizes @xmath71 , we have @xmath387 therefore we have @xmath388 hence we conclude @xmath389 similarly we can deduce @xmath390 on the other hand , it is not hard to deduce from the continuity of @xmath391 that @xmath392 hence @xmath393 * proof of theorem [ thm : main ] . * since @xmath394 and any circle with center in @xmath10 has measure zero by lemma [ rud ] , we may choose @xmath236 so that @xmath395 . by lemma [ lem : thicken1 ] , theorem [ thm:6.1 ] and lemma [ aux ] , we have @xmath396 similarly , @xmath397 since @xmath398 is a finite number independent of @xmath27 , the above proves that @xmath399 [ section ] [ section ] [ section ] let @xmath400 be a cat(-1 ) space , and @xmath401 a discrete , non - elementary subgroup of isometries of @xmath402 . denote by @xmath403 the visual boundary of @xmath402 , @xmath404 , @xmath405 the critical exponent of @xmath401 , which is assumed finite , @xmath18 the patterson - sullivan density for @xmath401 , and @xmath406 the associated bowen - margulis - sullivan measure . we shall assume that the length spectrum is non - arithmetic , and that @xmath406 is of finite mass ; remark that all these hypotheses are satisfied in the case of geometrically finite groups on hyperbolic spaces . first , let us state roblin s theorem . a simplified version ( where @xmath407 does not depend on the second coordinate ) appeared in @xcite . the argument divides into three steps : first , we show a quantitative estimate for the recurrence of the action of @xmath401 on the set of geodesics , of independent interest . second , we show that the quantity on the left - hand side above does not depend too much on @xmath414 . third , we integrate over @xmath414 to be able to apply roblin s theorem . define @xmath415 to be the set of bi - infinite oriented geodesics on @xmath402 , and let @xmath416 be the set of isometric embedding of @xmath409 to @xmath402 . the geodesic flow @xmath417 is the time - shift @xmath418 , and the canonical projection @xmath419 is the map @xmath420 . we shall make the usual identification @xmath421 and this can be done in such a way that @xmath422 is the point of the geodesic from @xmath71 to @xmath423 closest to a fixed reference point @xmath424 . in such coordinates , the geodesic flow is just @xmath425 , whereas the action of @xmath401 on @xmath416 defines a cocyle @xmath426 , such that for any @xmath427 , we have @xmath428 note that @xmath429 is the distance between the projections of @xmath430 and @xmath431 on the geodesic from @xmath71 to @xmath423 , and recall ( see ( * ? ? ? * corollary 5.6 ) ) that in cat(0 ) spaces , projection on a closed convex set is uniquely defined and @xmath382-lipschitz , so the following inequality holds for any @xmath432 , @xmath433 : @xmath434 for @xmath441 , define @xmath442}(\gamma v).\ ] ] since @xmath401 is discrete and acts properly on @xmath416 , and @xmath443 $ ] is a compact subset of @xmath416 , it follows that @xmath407 is uniformly bounded by some constant @xmath444 depending only on @xmath98 . choose @xmath445 , @xmath439 and let @xmath432 such that @xmath446 , and @xmath447 . define @xmath448 , then @xmath449 . thus , let @xmath407 be a continuous function on @xmath408 . define @xmath456 let @xmath457 , then since @xmath407 is uniformly continuous , there exists a neighborhood @xmath458 of the diagonal in @xmath459 such that for any @xmath460 and any @xmath461 , @xmath462 . let @xmath98 be the complement of @xmath458 , which is a compact subset of @xmath435 . so @xmath463 by proposition 1 , the last sum contains at most @xmath464 terms , so for sufficiently large @xmath27 , @xmath465 this proves that @xmath466 does not depend too much on @xmath414 for large @xmath27 , so for any @xmath414 , its value is close to the integral with respect to any probability measure . fix @xmath260 , it will then be sufficient to prove that the function @xmath467 has limit @xmath468 as @xmath469 ; indeed , recall @xcite that the orbital function satisfies @xmath470 define the map @xmath471 for any @xmath472 and any @xmath473 by : @xmath474 and extend @xmath471 when @xmath475 is in the limit set @xmath476 , to be equal to @xmath477 . then @xmath471 is continuous on @xmath478 . by tietze - urysohn s theorem , @xmath471 can be extended to a continuous function , still denoted by @xmath471 , on @xmath408 , and moreover @xmath479 . then @xmath480 @xmath481 and by roblin s theorem applied to the function @xmath471 , we conclude that @xmath482 has limit @xmath483 as @xmath469 , as desired . + _ acknowledgments_. maucourant wishes to thank thomas roblin for suggesting improvements on the hypotheses . gregory margulis . . springer monographs in mathematics . springer - verlag , berlin , 2004 . with a survey by richard sharp : periodic orbits of hyperbolic flows , translated from the russian by valentina vladimirovna szulikowska . marc peign . on the patterson - sullivan measure of some discrete group of isometries . , 133:7788 , 2003 . thomas roblin . sur lergodicit rationnelle et les proprits ergodiques du flot godsique dans les varits hyperboliques . = ergodic theory dynam . systems , ( 20 ) , 17851819 , 2000 .
we investigate the distribution of orbits of a non - elementary discrete hyperbolic subgroup @xmath0 acting on @xmath1 and its geometric boundary @xmath2 . in particular , we show that if @xmath0 admits a finite bowen - margulis - sullivan measure ( for instance , if @xmath0 is geometrically finite ) , then every @xmath0-orbit in @xmath3 is equidistributed with respect to the patterson - sullivan measure supported on the limit set @xmath4 . the appendix by maucourant is the extension of a part of his thesis where he obtains the same result as a simple application of roblin s theorem . our approach is via establishing the equidistribution of solvable flows on the unit tangent bundle of @xmath5 , which is of independent interest .
in march 2010 a total of 32 tanganyika killifish were collected with hand nets at the shore of lake tanganyika in the democratic republic of the congo at three study sites : kisokwe ( 41431 s , 291035 e ) , mufazi ( 70512 s , 295445 e ) , and mugayo ( 64651 s , 293342 e ) on the north western shore . the fish were killed immediately after collection by severing the spinal cord , the gills were removed , and parasite specimens were fixed intact on the gills in acetoformaldehyde alcohol ( afa ) solution and preserved in 70% ethanol . the position of attachment was recorded according to the regions suggested by gelnar ( 1987 ) , and data were subjected to statistical analysis ( pearson 's chi - square test ) to compare attachment to the left gill and right gill arches . differences between the dorsal , ventral , and medial attachment , as well as the distal , proximal , and central regions were also tested . ergasilus specimens for scanning electron microscopy were hydrated , freeze dried , and sputter - coated with gold and studied with a jeol 5600 scanning electron microscope . tissue samples for histology were dehydrated , infiltrated with resin , and 5-m serial sections were made . sections were stained with a heidenhains azan trichrome stain ( humason 1979 ) and studied and micrographed . the prevalence at mugayo was 90% , the mean intensity was 6.9 , and the abundance was 6.5 ; at kisokwe there was 100% prevalence , mean intensity was 18 , and an abundance was 18 ; at mufazi ( near momba ) prevalence was 70% , mean intensity was 7.8 and abundance was 5.6 . the overall mean prevalence was therefore 86.40% , the mean intensity was 7.56 , and the mean abundance was 6.38 . pearson 's chi - square test was used to compare attachment on left or right gill arches , and attachment to dorsal , ventral , and medial areas as well as between distal , proximal , and central regions . results for preference for either gill arch indicated that e. sarsi do not have a preference for either one of the gill archers ( p = 0.12 ) . related to the distribution of e. sarsi on the gill arch ( dorsal , median , ventral , distal , central and proximal ) , the pearson 's chi - square results indicated a significant difference ( p = 0.0005 ) between the dorsal , median and ventral ; however , no significant difference ( p = 1.19 ) occurred for distal , central , and proximal ( figure 1 ) . furthermore , an equal number of parasites occur on the four gill arches ( p = 7.88 ) , gill - arch 2 having the most parasites ( figure 2 ) . bar graphs illustrating ( a ) the number ( n ) of e. sarsi parasites on tanganyika killifish along the long- axis of the gill arch , and ( b ) the distribution of parasites along the short - axis attachment sites . the number ( n ) of e. sarsi parasites across the four gill arches of tanganyika killifish . the results indicate an unequal distribution of parasites between all the attachment sites . however , the distribution between the left and right sides of the host is equal . histological examinations of tanganyika killifish gill tissue infested with e. sarsi showed that mature females attach only to the tips of the primary lamellae , confirming fryer 's ( 1965 ) observation . the second antennae are modified into claw - like structures , and these are inserted into the gill tissue ( figures 3a , b , 4a ) . photomicrographs showing ( a ) the attachment of e. sarsi , to the primary lamella of tanganyika killifish ( the white arrow indicates the parasite 's 2nd antennae wrapped around the filament ) , and ( b ) e. sarsi parasites attach to the tip of the filament ( circles ) . photomicrographs of gill tissue of tanganyika killifish in close proximity to e. sarsi to show the histology ( stained with azan ) . micrographs showing ( a ) the pathological alterations caused by attachment ; where the parasite maxiliped is inserted into the gill tissue ( white arrows ) , and ( b ) a ruptured blood vessel ( white arrow ) , haemorrhage ( black arrow ) , tissue erosion ( striped arrow ) , and mucus strand and blood cells ( colorless arrow ) . ] following attachment and feeding erosion of the gill superficial epidermal tissue occurred adjacent to the second antennae , maxillipeds , and swimming legs ( figure 4b ) , and eventually the tip of the filament is lost ( compare figures 4b and 5a ) . increased mucus secretion occurs and the parasite and epithelium becomes covered by it . an increase in the number of mast and rodlet cells occurs in the vicinity of the parasite ( figure 5b ) . photomicrograph of ( a ) noneroded gill epithelium of tanganyika killifish , the circle shows the tissue that becomes eroded ( compare with b ; white arrow points to epithelium lifting ) , and ( b ) the inflammatory response of the host ; arrows show rodlet cells and mast cells . the maxillipeds and legs scrape pieces of tissue off to expose and break the underlying blood vessels , thereby causing bleeding ( figure 5b ) . gill epithelium , mucus strands , and extra vesicular blood cells occur in the area surrounding the maxillipeds ( figure 4a ) . these tissues are also present in the lumen of the buccal cavity and in the intestine of the parasite ( figure 6a ) . epithelial hyperplasia occurs along the length of the gill filament and results in fusion of gill lamellae ( figure 6b ) . ( a ) a cross section through e. sarsi ( white arrow ) in the vicinity of the buccal cavity . red blood cells are present in the oesophagus and gill tissue consisting of blood cells and tissue are present in the circle adjacent to the buccal cavity . ( b ) micrograph showing secondary lamellar fusion ( circle ) and parasite egg sacks ( white arrow ) . the anterior end of the parasite becomes embedded in the gill filament ( figure 7a ) . copious amounts of mucus are excreted onto the cell surface adjacent to the parasite 's attachment site as well as the gill filament in close proximity . figure 7b shows the swimming legs of the parasite that is responsible for some of the pathological alterations . the scraping action of the swimming legs removes gill tissue off the gill filament and pushes it towards the mouth . ( a ) scanning electron micrograph showing attached e. sarsi dorsal view ( circle ) . the adjacent filament is covered by mucus ( striped arrow ) and the white arrow shows the swimming legs . ( b ) swimming legs of e. sarsi covered by mucus ( white arrows ) . the prevalence at mugayo was 90% , the mean intensity was 6.9 , and the abundance was 6.5 ; at kisokwe there was 100% prevalence , mean intensity was 18 , and an abundance was 18 ; at mufazi ( near momba ) prevalence was 70% , mean intensity was 7.8 and abundance was 5.6 . the overall mean prevalence was therefore 86.40% , the mean intensity was 7.56 , and the mean abundance was 6.38 . pearson 's chi - square test was used to compare attachment on left or right gill arches , and attachment to dorsal , ventral , and medial areas as well as between distal , proximal , and central regions . results for preference for either gill arch indicated that e. sarsi do not have a preference for either one of the gill archers ( p = 0.12 ) . related to the distribution of e. sarsi on the gill arch ( dorsal , median , ventral , distal , central and proximal ) , the pearson 's chi - square results indicated a significant difference ( p = 0.0005 ) between the dorsal , median and ventral ; however , no significant difference ( p = 1.19 ) occurred for distal , central , and proximal ( figure 1 ) . furthermore , an equal number of parasites occur on the four gill arches ( p = 7.88 ) , gill - arch 2 having the most parasites ( figure 2 ) . bar graphs illustrating ( a ) the number ( n ) of e. sarsi parasites on tanganyika killifish along the long- axis of the gill arch , and ( b ) the distribution of parasites along the short - axis attachment sites . the number ( n ) of e. sarsi parasites across the four gill arches of tanganyika killifish . the results indicate an unequal distribution of parasites between all the attachment sites . however , the distribution between the left and right sides of the host is equal . histological examinations of tanganyika killifish gill tissue infested with e. sarsi showed that mature females attach only to the tips of the primary lamellae , confirming fryer 's ( 1965 ) observation . the second antennae are modified into claw - like structures , and these are inserted into the gill tissue ( figures 3a , b , 4a ) . photomicrographs showing ( a ) the attachment of e. sarsi , to the primary lamella of tanganyika killifish ( the white arrow indicates the parasite 's 2nd antennae wrapped around the filament ) , and ( b ) e. sarsi parasites attach to the tip of the filament ( circles ) . photomicrographs of gill tissue of tanganyika killifish in close proximity to e. sarsi to show the histology ( stained with azan ) . micrographs showing ( a ) the pathological alterations caused by attachment ; where the parasite maxiliped is inserted into the gill tissue ( white arrows ) , and ( b ) a ruptured blood vessel ( white arrow ) , haemorrhage ( black arrow ) , tissue erosion ( striped arrow ) , and mucus strand and blood cells ( colorless arrow ) . following attachment and feeding erosion of the gill superficial epidermal tissue occurred adjacent to the second antennae , maxillipeds , and swimming legs ( figure 4b ) , and eventually the tip of the filament is lost ( compare figures 4b and 5a ) . increased mucus secretion occurs and the parasite and epithelium becomes covered by it . an increase in the number of mast and rodlet cells occurs in the vicinity of the parasite ( figure 5b ) . photomicrograph of ( a ) noneroded gill epithelium of tanganyika killifish , the circle shows the tissue that becomes eroded ( compare with b ; white arrow points to epithelium lifting ) , and ( b ) the inflammatory response of the host ; arrows show rodlet cells and mast cells . the maxillipeds and legs scrape pieces of tissue off to expose and break the underlying blood vessels , thereby causing bleeding ( figure 5b ) . gill epithelium , mucus strands , and extra vesicular blood cells occur in the area surrounding the maxillipeds ( figure 4a ) . these tissues are also present in the lumen of the buccal cavity and in the intestine of the parasite ( figure 6a ) . epithelial hyperplasia occurs along the length of the gill filament and results in fusion of gill lamellae ( figure 6b ) . ( a ) a cross section through e. sarsi ( white arrow ) in the vicinity of the buccal cavity . red blood cells are present in the oesophagus and gill tissue consisting of blood cells and tissue are present in the circle adjacent to the buccal cavity . ( b ) micrograph showing secondary lamellar fusion ( circle ) and parasite egg sacks ( white arrow ) . [ figure available online in color . ] scanning electron micrographs corroborated the observations from the histological sections . the anterior end of the parasite becomes embedded in the gill filament ( figure 7a ) . copious amounts of mucus are excreted onto the cell surface adjacent to the parasite 's attachment site as well as the gill filament in close proximity . figure 7b shows the swimming legs of the parasite that is responsible for some of the pathological alterations . the scraping action of the swimming legs removes gill tissue off the gill filament and pushes it towards the mouth . ( a ) scanning electron micrograph showing attached e. sarsi dorsal view ( circle ) . the adjacent filament is covered by mucus ( striped arrow ) and the white arrow shows the swimming legs . ( b ) swimming legs of e. sarsi covered by mucus ( white arrows ) . although e. sarsi was previously reported from lake tanganyika ( sars 1909 ; cunnington 1920 ; capart 1944 ; fryer 1965 ) , this is the first report for this host , the tanganyika killifish , and of the pathological alterations associated with it . fryer ( 1965 ) observed that a correlation exists between the attachment site of various ergasilus species and pathological alterations elicited ; he also noted that different species attach to different regions , even on the same host . e. sarsi bears long antennae that lack spines enabling it to wrap around a gill filament and predominantly attach to the tip of the gill filament where the filament is narrower . changes were noticed on the gill surface along the entire length of the parasite 's body even to the position where the swimming legs and egg sacks occur . gill fusion and lamellar lifting occurred and this impacts the function of the gill in osmoregulation , as well as respiratory gas exchange . furthermore , host tissue was scraped of in the vicinity of the appendages indicating that traumatic alterations are not limited to the action of the mouth parts but that all appendages participate . host cells were observed in the intestine of the parasite , indicating that the parasite actively feed on the host , consuming gill tissue as well as blood . the presence of rodlet cells indicate that an immune response was elicited , confirming an observation by dezfuli et al . this effect is enhanced by high temperature in the tropics , which causes a reduction of the oxygen binding ability of water , creating additional stress to the host fish . the parasites occur mostly on the second gill arch , which is also the arch that receives the strongest water current , an advantageous locality for distribution of the parasite 's eggs in the surrounding water column . according to butler ( 2013 ) tanganyika killifish require very specific breeding conditions and therefore it is challenging to breed in captivity , but butler mentions , nevertheless , that the fish provides great enjoyment in a tropical tank because of its beauty . e. sarsi is not a species - specific parasite ( oldewage and avenant - oldewage 1993 ) and indigenous fishes in importing countries may therefore become infested unintentionally .
a total of 204 ergasilus sarsi , a copepod , were collected from tanganyika killifish lamprichthys tanganicanus in lake tanganyika during march 2010 . the prevalence was 86.40% , the mean intensity was 7.56 , and the mean abundance was 6.38 . only 27 of the fish were infested , and the highest infestation on one fish was 29 . proliferation of mucus cells and lamellar fusion occurred . haemorrhage due to blood vessel compression was noted . this is the first record of e. sarsi from tanganyika killifish . this study is also the first to provide a description of the pathological alterations caused by e. sarsi .
malaria remains a significant burden in sub - saharan africa as it continues to be the leading cause of infant morbidity and mortality in africa . it is believed that malaria contributes up to about 25% of infant mortality in nigeria . furthermore , in areas of africa with stable transmission , plasmodium falciparum infection during pregnancy is estimated to cause as many as 10,000 maternal deaths each year , 8% to 14% of all low birth weight babies , and 3% to 8% of all infant deaths . thus , malaria burden , if not reduced , poses a threat to the attainment of the millennium development goals 4 and 6 . congenital malaria is defined as malaria in a newborn or infant , transmitted from the mother . congenital malaria is generally defined as malaria acquired by the fetus or newborn directly from the mother , either in utero or during delivery . it is also defined as the presence of malarial parasites in the peripheral smear of the newborn from twenty four hours to seven days of life . malaria is considered to be congenital in the neonate when asexual parasites are detected in the peripheral blood within the first week of life [ 6 , 7 ] . congenital malaria was thought to be rare in developing countries [ 8 , 9 ] . firstly , the protective effect of the foetal haemoglobin ( hbf ) in a newborn is expected to exert its influence during the immediate neonatal period [ 10 , 11 ] . secondly , local health facilities in resource - limited settings often lack the capacity to diagnose malarial infection [ 1214 ] . thirdly , the clinical signs of neonatal malaria may be indistinguishable from those of neonatal sepsis . thus , congenital malaria might pass unnoticed , and this might be responsible for its underreporting . therefore , the aim of this paper was to highlight the prevalence and burden of congenital malaria in sub - saharan africa as well as the challenges of its diagnosis and prevention ; the findings were used to suggest measures aimed at strengthening health systems and reducing the burden of congenital malaria in the population . literature providing information on the prevalence , burden , diagnosis , prevention , and control of congenital malaria , published between 2000 and 2010 was reviewed . congenital , malaria , burden , diagnosis , prevention , control , and sub - saharan africa . these literatures were accessed from pubmed ( medline ) , biomed central , google scholar , and cochrane database of systematic reviews . searches were also supplemented with recommendations from outside experts , reviews of bibliographies of other relevant articles , and systematic reviews . congenital malaria is rare in developed countries such as the united states of america , where only three infants out of 4.1 million live births were reported to have congenital malaria . the situation is however different and widely varied in sub - saharan african countries . to this end , recent reports have suggested that congenital malaria is not as rare in developing countries as previously thought . for example , in a survey covering seven sites in sub - saharan africa , fischer showed a mean prevalence rate of 7% for congenital malaria ( range 023% ) . furthermore , while a study in kenya reported a prevalence of malarial parasitaemia in < 0.5% of neonatal admissions , high prevalence of congenital and neonatal parasitaemia ( > 20% ) was reported in uganda and zambia . a study done in ghana revealed an incidence of 13.6% congenital malaria infections . in nigeria , congenital malaria was documented in 13.6% of babies at delivery . in another multicentre study in nigeria , have reported a congenital malaria prevalence rate of 17.4% among sick neonates in a tertiary hospital in southwestern nigeria . it is estimated that placental malaria is responsible for 35% of preventable low birth weight in developing countries . it is also associated with intrauterine growth restriction , prematurity due to preterm labour and intrauterine foetal death . malaria in pregnancy is reported to cause between 75,000 and 200,000 infant deaths each year in sub - saharan africa . the detection of malaria parasites in the infant 's blood is essential for diagnosis , although blood smears can be negative if there are low parasite counts ( 50 parasites/l blood ) . pengsaa suggested that three repeated blood smears over 48 hours should be reported negative before excluding the diagnosis . the capacity to conduct blood test for the diagnosis of congenital malaria is however limited in sub - saharan african countries . this is because studies have shown a persistent lack of capacity to conduct quality malaria diagnostic tests by local health facilities [ 1214 ] . the use of pcr has suggested that congenital malaria may be more frequent , although it is unclear if a positive pcr represents an active infection . though , pcr is a more sensitive and accurate diagnostic technique than blood smear microscopy , its use is however very limited in developing countries as it is expensive and requires a specialized laboratory . apart from the laboratory constraints , low antenatal care attendance and skilled delivery rates in african countries will also affect detection and prevention of congenital malaria . antenatal care utilization in the developing countries is about 65% ; this is low compared to that of the developed countries , which is 97% . the implication is that in about two thirds of pregnant women in sub - saharan africa , opportunities for early recognition and prompt treatment of malaria infection are missed . this is because its clinical findings may be indistinguishable from those of neonatal sepsis ; hence , the condition is either detected late or not even suspected unless neonates are specifically screened for it . furthermore , as with many congenital infections , the new born child can manifest with fever , irritability , feeding problems , hepatosplenomegaly , anemia , jaundice , and low birth weight . thus , the clinical distinction from other congenital infections rests primarily on maternal history of exposure to malaria and absence of a skin rash . a study done in calabar , nigeria , reported that 35% of newborns with clinical signs of neonatal sepsis were found to have congenital malaria . fever was the most common feature reported by studies in kenya and nigeria among others , which include refusal to feed or poor feeding , irritability , anaemia , hepatosplenomegaly , and jaundice . prevention of any disease condition requires the availability of methods for prediction of those at high risk of the disorder . if there were tests which are adequately sensitive for detecting placenta malaria in the antenatal period , it would have helped in assessing the efficacy of antimalarial drug during pregnancy and identifying the infants at risk of congenital malaria . however , there are no tests which are adequately sensitive for detecting placental malaria ; hence , the difficulty in identifying those at high risk of this condition . therefore , malaria preventive measures in pregnancy still remain as priority interventions required to protect the foetus and the newborn against the adverse effects of congenital malaria . the world health organization ( who ) has recommended a three - pronged strategic framework in areas of high or moderate ( stable ) malaria transmission of sub - saharan africa : intermittent preventive therapy ( ipt ) , insecticide - treated nets ( itns ) , and case management of malaria illness and anaemia . intermittent preventive therapy ( ipt ) , also known as chemoprophylaxis for pregnant women , especially those in their first pregnancies , has been widely used in sub - saharan africa . in line with who recommendation , most national guidelines stipulate that all pregnant women should receive at least two doses of ipt given as sulphadoxine - pyrimethamine ( sp ) combination after quickening as part of preventive treatments at antenatal care . for example , researchers in kenya and malawi have shown that intermittent preventive therapy with sulphadoxine - pyrimethamine significantly reduces the prevalence of maternal anaemia and placental parasitaemia , and the incidence of low birth weight [ 2932 ] . furthermore , sulphadoxine - pyrimethamine has been found to be safe in pregnancy and efficacious in reproductive - age women ; hence , its strong acceptance and coverage levels of greater than 80% for the first dose . despite the beneficial impact of sulphadoxine - pyrimethamine on maternal and infant health , its utilization is threatened by weak health systems and sociocultural issues in sub - saharan africa . studies have shown that a substantial proportion ( 20% to 80% ) of pregnant women in this setting make their first antenatal visit in their third trimester [ 3335 ] . furthermore , unbooked pregnancies are common [ 36 , 37 ] , and antenatal care utilization rate ( i.e. , antenatal care clinic attendance of at least once during most recent pregnancy ) varies from 60% to 90% [ 1 , 38 , 39 ] . these findings could be partly attributed to low quality of service and sociocultural reasons . while evidence abound on the persistent declining quality of antenatal services provided to pregnant women [ 33 , 35 , 40 ] , other researchers have found that perceived quality of service was the most important factor which influenced the choice of facility for obstetric care ; similarly , a perceived lack of quality in the antenatal care was associated with a late first antenatal visit in kenya . within the sociocultural context , it is thought that noninitiation of care in the first trimester seems to be a widespread cultural practice in sub - saharan africa . in rural gambia , women do not usually announce pregnancy but wait for other family members to discover it , thereby presenting for care well into the third trimester . while further qualitative research is required to explore the extent to which late first antenatal visit is affected by cultural practices , the implication of the findings is that a substantial proportion of pregnant women always remains unprotected against malaria infection because of missed opportunity of treatment in the second trimester . this therefore exposes fetuses of such unprotected women to placental malaria and its adverse effects , thereby contributing to the challenges militating against prevention of congenital malaria . this situation is further worsened by the practice of partial preventive treatments , including sulphadoxine - pyrimethamine ( sp ) therapy provided by health workers at antenatal care service [ 33 , 35 , 43 ] . randomized control trials in sub - saharan africa have consistently shown the effectiveness of insecticide - treated nets ( itns ) in the prevention of malaria in pregnancy . studies in ghana and kenya have documented reduced placental malaria , low birth weight , and fetal loss resulting from use of itns . though the use of insecticide - treated nets ( itns ) is reportedly considered as the most cost - effective method of malaria prevention in highly endemic areas , there have always been some concerns about the preventive strategy in sub - saharan africa ; these concerns include access , cost , retreatment , and gaps between ownership and use of itn . access to itns by vulnerable populations including pregnant women continues to increase due to the efforts of national governments and supporting development agencies through multiple approaches such as stand - alone campaigns , health facilities , and antenatal clinic [ 1 , 38 ] . access is also enhanced by free distribution and sales of itns at subsidized cost or through discounted voucher systems [ 1 , 38 , 45 ] , while the introduction of long - lasting insecticidal nets ( llins ) has reduced the burden of frequent retreatments . despite these efforts , recent findings revealed low utilization of itns among pregnant women . though increasing trends in ownership and use of itns by households were reported in national demographic surveys , the reports indicated that 5% to 57% of pregnant women aged 1549 years slept under an itn the past night . furthermore , gaps between ownership and use of an itn continue to exist as about 50% or less of pregnant women aged 1549 years in households with an itn slept under the net the past night [ 1 , 38 , 46 , 47 ] . supporting and promoting access to correct , affordable , and appropriate treatment within 24 hours of the onset of symptoms of malaria is the third essential component of malaria prevention and control during pregnancy in malarious endemic countries of sub - saharan africa . the world health organization ( who ) had recommended chloroquine ( cq ) in chloroquine - sensitive areas and sulphadoxine - pyrimethamine ( sp ) in areas with cq resistance for treatment of uncomplicated malaria in pregnancy . quinine is another alternative in areas where both cq and sp are not effective . however , prompt and effective case management of malaria illness is hinged on early and correct diagnosis of the condition . as noted above , this is seriously hindered by lack of capacity to conduct quality malaria diagnostic tests by local health facilities in sub - saharan african countries [ 1214 ] . while this situation might have justified the presumptive treatment of fever with antimalarials ( i.e. , treating all febrile episodes suspected of malaria with a full therapeutic dose of antimalarials ) , such practice might have led to a reduced susceptibility of parasites to the commonly used antimalarial drugs in these settings . the world health organization ( who ) recently recommended prompt parasitologic confirmation by microscopy or alternatively by rapid diagnostic tests ( rdts ) in all patients suspected of malaria before treatment findings from the previous review revealed that many peripheral health facilities in resource - poor settings of sub - saharan africa lacked the capacity to conduct quality parasitological diagnosis of malaria by microscopy ; this is because the procedure is labour - intensive requiring trained staff and quality equipment [ 49 , 50 ] . on the other hand , malaria rapid diagnostic testing ( rdt ) has been found useful as an attractive alternative to routine microscopy with good sensitivity and specificity profiles [ 48 , 51 ] . in addition , rdts have the potential to be cost - effective , require no capital investment or electricity , are simple to perform , and are easy to interpret [ 51 , 52 ] . if appropriately introduced and implemented , it also has been shown to have the potential of improving drug - prescribing behaviour of health workers , thereby reducing overtreatment of malaria and the problem of drug resistance . from the foregoing , utilization of rdts in resource - poor settings would seem to be an appropriate technology as it has the potential of improving the quality of malaria diagnosis and treatment services provided to all cases of malaria , including pregnant women and newborns . therefore , it is suggested that national governments and development partners in sub - saharan africa should support widespread use of rapid diagnostic tests ( rdts ) for malaria diagnosis . the capacity of local health facilities providing maternal and child health services should be strengthened with the provision of adequate supplies of equipment and consumables required to provide the diagnostic services . in addition , targeted trainings and supportive supervision of local health staff are highly desirable in order to meet up with the challenges of newly - assigned task . in order to increase uptake of ipts and facilitate prompt diagnosis and treatment of malaria in pregnancy , national governments and development partners in sub - saharan african countries should also consider improving the poor maternal health service indicators nonbooking , late antenatal visits and low antenatal service rate as an essential task to be concertedly pursued . to achieve this task , strategies aimed at improving maternal health service for example , proven - specific interventions such as the world health organization ( who ) training on life saving skills are suggested for use of maternal health service managers in addressing the weak health systems . periodic trainings conducted for local health staff can help address and strengthen health systems , particularly if targeted at previously reported areas of deficiency such as declining quality of maternal health service , poor record keeping practices of health workers , and poor utilization of intrapartum monitoring tools such as a partograph [ 33 , 34 , 55 ] . in addition , health staffs ' familiarization and adherence to who guidelines on provision of effective , efficient , safe , and culturally appropriate services to pregnant women and newborn under the integrated management of pregnancy and childbirth ( impac ) would assist to ensure best practices . it is expected that these efforts would improve utilization of maternal health services , increase ipt uptake , enhance prompt diagnosis and treatment of malaria in pregnancy , and consequently prevent congenital malaria . on a long term basis , strategies which would bring about over 80% antenatal service utilization rate should be pursued vigorously . therefore , it is suggested that redirecting and repackaging health education and service content of antenatal care service using a social marketing approach acceptable within the sociocultural context would be found useful . therefore , placing the antenatal care service content and its benefits on public agenda through different media and matrices may be helpful in the study setting as opposed to the current practice of restricting information to women who make antenatal visits . despite male economic dominance and decision making power in developing countries , however , studies had shown that male involvement would significantly improve indicators of maternal health service utilization , and , therefore , it could also improve uptake of ipts and case management of malaria in pregnancy . hence , it is recommended that father 's roles in maternal health be defined , packaged , and incorporated in the antenatal care service messages meant for dissemination to the public . with regard to closing the gap between ownership and use of an itn , a carefully designed qualitative research may be useful in eliciting the factors responsible or reasons for not sleeping under an itn despite its availability in the household . while it is suggested that national governments and development partners should not relent on their efforts in making itns universally accessible to pregnant women either free of charge or at a subsidized price , experiences of other researchers on factors which promote or inhibit itn usage may be found useful in packaging educational messages aimed at promoting its usage . itn usage promoting factors such as high perception on the seriousness of malaria and its effect on pregnant women and children , high perceived benefit of itns in protecting children and pregnant women against malaria , and high awareness of the prevention of malaria as a better and cheaper option compared with treatment should be intensified . whereas inhibitory factors such as fear of the chemical that is used to treat nets and unsupportive spouses should be demystified . evidence abound that congenital malaria constitutes a public health burden in sub - saharan africa . however , efforts of the national governments and development partners at instituting the recommended cost - effective interventions are continuously thwarted by challenges brought about by weak health systems and sociocultural factors among others , thereby , militating against the progress towards attainment of millennium development goal ( mdg ) 6 ( indicator 22 , target 8) . health system strengthening and appropriate public health promoting and educating messages delivered through a social marketing approach may be found useful in putting back on track the race towards 2015 with respect to attainment of mdg 6 .
objectives . review of burden of congenital transmission of malaria , challenges of preventive measures , and implications for health system strengthening in sub - saharan africa . methods . literature from pubmed ( medline ) , biomed central , google scholar , and cochrane database were reviewed . results . the prevalence of congenital malaria in sub - saharan africa ranges from 0 to 23% . diagnosis and existing preventive measures are constantly hindered by weak health systems and sociocultural issues . who strategic framework for prevention : intermittent preventive therapy ( ipt ) , insecticide - treated nets ( itns ) , and case management of malaria illness and anaemia remain highly promising ; though , specific interventions are required to strengthen the health systems in order to improve the effectiveness of these measures . conclusion . congenital malaria remains a public health burden in sub - saharan africa . overcoming the challenges of the preventive measures hinges on the ability of national governments and development partners in responding to the weak health systems .
the study of spinodal decomposition and coarsening in quenched ising models has been vigorously pursued@xcite . binder and stauffer@xcite predicted that , following a quench at @xmath10 , the structure function of a coarsening system would grow with a single length scale @xmath11 . numerical studies have verified that , when this length scale is removed from the results , the reduced structure factor is very nearly constant in time@xcite . lifshitz and slyozov@xcite gave a further prediction : domain size should asymptotically grow as @xmath12 for a conserved order parameter ( cop ) model . monte carlo simulations @xcite have checked this result . all of this theory describes the equilibrium case , where nothing acts on the coarsening process besides a thermal bath . in real systems , however , phase segregation can be affected by several influences , including gravity , elastic stress , or electric fields . such forces often push material around , instead of preferring one phase over another . given this wide area of potential experimental application , it seems reasonable to ask : what happens when you take a cop ising model and apply a uniform force to push particles ( up spins ) across the lattice ? this type of model was first introduced by katz , lebowitz , and spohn@xcite , who found that the external driving force raised @xmath13 . subsequent research has carefully investigated the ordering phase transition of this model.@xcite in addition to work which analyzed interface roughness@xcite and domain shape@xcite , one study has checked to see whether the scaling and growth law results of the equilibrium model can carry over to the nonequilibrium one@xcite . such studies of the driven diffusive lattice gas ( ddlg ) have almost always employed the same monte carlo dynamics those of kawasaki @xcite . for this specific class of model , there is no barrier to hinder particle motion along the interface between two phases , and domains tend to elongate along the direction of the force . when considering a directionally averaged measure of domain size , however , yeung _ et al . _ @xcite . found that the kawasaki form of the ddlg showed familiar @xmath14 coarsening behavior . the present study finds that this slow rate of coarsening , as well as the orientation of domains , is model - dependent . noting that nonequilibrium problems have an inherent sensitivity to dynamics , we have studied a ddlg with particle mobility that goes down when the number of bonds to neighbors goes up . the resulting motion has free diffusion of single particles across empty spaces . ( a similar bond counting approach was used to model electromigration of thin films on semiconductors@xcite , but that work did not study coarsening . ) in our model , the external driving force bunches domains up along the field ( so that they lengthen in the transverse direction ) , and it can push entire domains of vacancies across the lattice so that they sweep up other vacancies and grow quickly . for moderate lattice fillings , the resulting domain radius grows as @xmath15 , where @xmath1 varies roughly from 0.4 to 0.7 . for high concentrations of particles , the early stages of growth can be _ exponential _ in time . when we approached the problem of coarsening in an electric field , we were interested in fast motion of isolated particles through the middle of a domain , rather than along an interface . such bulk diffusion was relevant to the electromigration studies of moeckly , lathrop , and buhrman@xcite . in their room temperature observations of yb@xmath7cu@xmath8o@xmath9 thin film devices , they found that a small electric bias ( @xmath16 cm ) could produce macroscopic motion of oxygen . the associated force was so tiny that it would only have moved an oxygen atom a few lattice constants per second in a fully oxygenated sample , where the activation energy for oxygen motion is about 1 ev @xcite and the diffusion constant is about @xmath17 near room temperature @xcite . in an oxygen depleted region , however , small forces may have a large impact : internal friction measurements give an activation energy of 0.1 ev for motion of a completely isolated oxygen atom , and the chemical diffusion data of lagraff _ et al._@xcite suggest that the diffusion constant of ybco can rise by more than an order of magnitude as the oxygen in the chain plains is depleted . to study the effects of such differences in mobility , we wanted the simplest model that could describe a density - dependent diffusion constant . we therefore chose a two dimensional ddlg with modified continuous monte carlo dynamics@xcite . thus , we group atoms according to their coordination @xmath18 , increment time by an amount which increases as the number of highly mobile atoms decreases , and propose a move from list @xmath18 with probability @xmath19= dt ( 4-q ) n(q ) e^{-4jq},\eqno(1)\ ] ] where @xmath20 $ ] is the number of @xmath18 coordinated atoms . this continuous monte carlo scheme satisfies detailed balance , so the equilibrium state at @xmath21 = 0 is that of the nearest neighbor ising model : @xmath22 . this dynamics allows atoms with low coordination to move quickly . it also produces a basic particle hole asymmetry , illustrated by the fact that isolated atoms can zip across vacant spaces ( rate 1 ) , while isolated holes hardly move ( rate @xmath23 ) . we include the electric potential by accepting all proposed forward moves , a fraction @xmath24 of the proposed sideways moves , and only @xmath25 of the proposed moves against the field , where @xmath26 is a local potential difference along the field@xcite . motivated by the ybco experiments , we have focused much of our attention on the limits of high particle concentration , relatively low fields , and strong coupling to nearest neighbors ( i.e. a highly concentration dependent mobility ) . figure [ snapshots ] shows two of the interesting behaviors we found . in both pictures , the black regions are vacancy clusters which move collectively downwards as an external force pushes ( white ) particles up . in the symmetry - breaking field , the vacancy blocks become short and wide @xcite . the pictures on the left ( fig . 1a and 1b ) have 90% lattice filling . here , isolated runaway processes dominate : large domains move much faster than small ones and sweep up many vacancies , thus becoming even bigger and faster . we discuss such processes in the following section on exponential growth . the pictures on the right have 70% lattice filling . here , blocks of all length scales are moving and combining , and a mean domain radius grows as a power in time . note that the late snapshot at the bottom ( fig . 1d ) resembles a scaled up version of the snapshot at the top ( fig . 1c ) . in section iii , we evaluate scaling collapses and we construct a simple picture for domain growth in this regime . finally , in section iv , we will look at small driving forces . in this limit , we find that the early stages of growth show the @xmath27 behavior expected for the zero field case , and then a crossover to fast growth occurs . we interpret this crossover as the time at which the area swept out through linear motion along the field equals the area visited by diffusive motion , and we derive the field dependence of the domain size at crossover . the runaway growth of the high filling regime is fundamentally tied to a separation of time - scales produced by faceting . the pictures in figure [ snapshots ] were generated with strong coupling between neighbors , so atoms with two neighbors moved much more quickly than atoms with three . in this regime , the base of each vacancy domain tends to be flat , with all atoms having three neighbors . after a stagnant period , one of these strongly pinned atoms pops out of the base and leaves behind two doubly coordinated particles . the remaining atoms then have a lower barrier to motion . one by one , the rest of the row soon dislodges and moves rapidly across the empty space . under such conditions , one would expect the velocity of a region to be proportional to its horizontal width ( i.e. the number of ways to produce the initial break ) . figure [ velvs_width ] shows this behavior at low temperatures for isolated vacancy domains . periodically , a domain will collide with a vacancy in its path and that will provide the initial break to move the domain through an extra row of atoms . again , the rate of such motion increases linearly with the width of the domain . domain size is therefore a crucial factor in determining growth . besides moving more quickly to sweep up new vacancies , wide blocks clear larger regions as they move . in general , we expect : @xmath28 here , @xmath29 is the area of the block in question , @xmath30 is its width , @xmath31 is the concentration of vacancies in the region ahead of it , and @xmath32 is the relative velocity of the block we are describing ( in comparison to that of vacancies which it overtakes ) . for low temperatures and low vacancy concentrations , small vacancy blocks will move at negligible velocities and large blocks will move with @xmath33 . in this regime we expect : @xmath34 if the width and height of a region scale similarly , then the above result gives : @xmath35 or @xmath29 growing exponentially in time . in practice , we find that width grows more quickly than height . this tendency should only enhance the rate of growth . to check this prediction against our simulation , we calculated two point correlation functions in both horizontal and vertical directions . for a rough measure of length - scales , we used the width at quarter max of each of our correlation functions@xcite . figure [ expgrowth ] shows vertical block size , horizontal block size , and the product of the two ( a typical domain area ) as a function of time . to run the simulation efficiently enough to observe a large range of size , we used a fast model with nearly infinite coupling ( where uncoordinated atoms always moved first , and then all singly coordinated atoms moved ) . as figure [ 90percent_3temps ] demonstrates , we found the same behavior at low temperature for standard finite coupling dynamics . note that the vertical scale on these plots is logarithmic , so the straight line observed does indicate exponential growth . notice that the runaway growth does not continue indefinitely . for very large domains , the time required to move a full row of atoms from bottom to top is comparable to the time between initial `` three moves '' . if the rate of @xmath36 moves is the limiting step , then motion from each kink in the domain can proceed independently and large blocks will approach a terminal velocity . crossover to this behavior will occur when the time required to move an entire row of atoms through sequential @xmath36 moves is approximately equal to the expected waiting time before one atom in that row moves from a triply coordinated site . the slowdown in growth in figure [ expgrowth ] occurs when these two time - scales are comparable to each other . figure [ velvs_width ] shows the velocity of a vacancy domain in an empty lattice as a function of domain width at two different temperatures . note that the low temperature plot is fairly linear , while the high temperature results do indeed approach a terminal velocity . figure [ 90percent_3temps ] shows simulation results with a domain roughening crossover which varies with temperature . there is another way to produce rough domain bases and eliminate exponential growth . in the case where vacancy clusters are constantly running into one another , their bases will always contain doubly coordinated atoms , and @xmath36 moves will again be the rate limiting step . figure [ near82_growth ] shows the changeover from exponential to power - law growth as the number of vacancies increases . looking at configurations with @xmath37 filling , we see isolated runaway domains whose acceleration slows as their bases become rough . this behavior makes intuitive sense because , in runaway growth , the size of large domains increases more quickly than the spacing between small ones , so large domains can grow to be larger than a typical interdomain spacing . we will find later that horizontal correlation functions in the power - law growth regime nearly scale , so the relationship between domain width and horizontal domain spacing remains nearly fixed . this is consistent with our observation that growth which starts in the crowded , power - law regime tends to stay power - law . we have found that the exponential growth regime occurs for low temperatures and low vacancy concentrations , where only a few domains become large enough to respond strongly to the external field . at lower particle fillings , most vacancies will join clumps soon after coarsening begins , since most of the vacancies are connected through atoms with single or double coordination at quench . at such fillings , vacancy domains no longer move through a nearly stationary sprinkling of tiny vacancy clumps . instead , the lattice contains a distribution of block sizes , most of which are moving steadily in the field . frequent collisions between domains provide sources of fast moving atoms , so that motion is not characterized by long waiting times with flat domain bases . thus , we no longer expect the velocity of a domain to be proportional to its width . figures [ collapses ] and [ near70growth ] show results from the simulation at lower fillings . the first , a check for dynamical scaling , gives clear evidence that domains of all length scales are growing at similar rates . the horizontal correlation function shows strong hints of scaling , but the vertical correlation function has an anticorrelation dip which grows more pronounced with time . ( that is , the regions between vacancy domains are becoming more thoroughly swept out . ) although growth in this regime is not completely self similar , a scaling picture may be a useful first step towards describing coarsening at these fillings . figure [ near70growth ] shows characteristic domain area as a function of time for 60% , 70% , and 80% concentrations . this growth is significantly faster than the @xmath2 behavior of a zero field model . if we fit growth at each concentration to @xmath38 , @xmath1 varies from about @xmath39 at 60% filling to approximately @xmath40 at 70% and 80% filling . although the behavior of our model in this moderately full regime is complex , we have tried to piece together a simple picture which would mimic the observations described above . we start with the question : in a scaling regime where growth is still dominated by catch up events , what kind of velocity distribution would produce linear domain growth ? an elementary argument proceeds as follows : we can describe each time in a scaling regime with characteristic horizontal and vertical length - scales @xmath41 and a @xmath42 . in a typical collision , the area gained by a vacancy cluster will scale with the product of these two lengths , i.e. @xmath43 a typical time between collisions will scale as the vertical length - scale divided by the velocity difference of the two colliding domains : @xmath44 together , these two results indicate that the area of a typical domain will increase linearly in time if @xmath45 . is this scaling picture useful for understanding simulation results ? one obvious objection is that vertical correlations in our model do not settle into a final scaling shape until late in the simulation , and so the typical vertical spacing between domains does not scale perfectly with the vertical height of the domains . also , we have neglected any enhancement in coarsening due to velocity fluctuations , and in fact our simulation results indicate that domain areas in this regime have somewhat faster than linear growth in time . realizing that our scaling picture is an approximate description , at best , we have investigated the size dependence of domain velocities . recall that a large domain with several kinks in its base should approach a terminal velocity where motion proceeds from each kink independently . is the dominant correction to this terminal velocity a term of the form @xmath46 ? note that this the form one might expect if the dominant correction is due to behavior at the sides of a domain base . figure [ velvs_invwidth ] shows velocity plotted against @xmath47 for domains of various size moving through empty space at high temperature , so that the domain bases had several kinks . we tried plotting velocity vs. @xmath48 and find the best asymptotic linear fit for @xmath49= .7 to 1.2 . figure [ velvs_invw_oc7 ] shows velocity as a function of @xmath47 in an actual simulation run at 70% filling . despite poor statistics in the latter plot , figures [ velvs_invwidth ] and [ velvs_invw_oc7 ] together seem to confirm that vacancy clusters in our model approach constant velocity with @xmath50 corrections . thus , our scaling picture may provide a first step towards explaining observed growth at these fillings . for fillings below @xmath51 , we must focus on domains of particles , instead of vacancies . these clumps of particles actually move against the field direction while a wind of particles sweeps into them on one side and tears particles away on the other . figure [ powers ] shows preliminary simulation results at these fillings . domain area grows roughly as @xmath52 at 20% filling ( @xmath53 ) , as @xmath54 at 30% filling ( @xmath55 ) , and as @xmath56 at 50% filling ( @xmath57 ) . note that growth at low fillings is dominated by the shorter time - scales associated with motion of atoms with few neighbors . note also that the growth exponent @xmath1 increases with filling . we do not at present have an explanation for the latter effect . for high fillings and strong interparticle couplings , we have seen that large external fields can dramatically enhance coarsening . in most experimental applications , however , the potential difference between neighboring sites is much less than @xmath58 , so it is natural to ask how weak fields affect domain growth . in the zero field limit , our model corresponds to standard lifshitz - slyozov growth with asymptotic @xmath27 behavior . slightly away from this limit , we find that low fields produce such slow coarsening for a while , and then generate a crossover to fast growth and noticeable anisotropy . figure [ crossover ] shows this behavior . first , initial transients die away on a time scale given by the rate of motion for @xmath59 atoms ( as in @xcite ) , and @xmath2 growth sets in . when the characteristic domain size is still much less than @xmath60 , growth takes off and the presence of the field also appears in a loss of square domain symmetry . figure [ cross_vsfield ] shows rough visual estimates of crossover length as a function of field . although this plot may include systematic error from pinpointing a crossover in increasingly rounded curves , it strongly suggests that the crossover length has a weak dependence on field . to gain a physical understanding of the crossover , first note that it represents a transition between diffusion - dominated growth , and driven collisions produced by the external field . in this low field regime , where the potential drop across the domain is still less than @xmath58 , we can describe the driven motion with linear response theory . we will argue that crossover occurs when a typical block absorbs more vacancies through concerted motion along the field than through diffusive motion . driven collisions should win when the area of a circle swept out through diffusion , @xmath61 , is equal to the area swept out by linear motion , i.e. @xmath62 note that we can replace the horizontal length scale @xmath30 with a general length scale @xmath63 , since this early growth regime is precisely when length scales in all directions are the same . to describe the crossover more completely , we need to know how @xmath64 and @xmath65 vary with the size of a domain in our model . for velocity , we refer back to the section describing exponential growth , where we found @xmath66 whenever motion was limited by the slow rate of dislodging the first atom from a row . to describe the variation of the diffusion constant , note that @xmath67 , where omega is the frequency of a typical move and @xmath68 is the center of mass displacement caused by such a move . for a faceted domain , a typical move takes an atom from one rare kink in the boundary to another . such a move displaces the atom by a distance of order @xmath63 and the center of mass by @xmath69 . since the frequency of these moves will be proportional to @xmath63 , we expect that faceted domains will have @xmath70 . note that these results for @xmath65 and @xmath64 are consistent with the einstein relation that should apply at such small fields:@xmath71 . ( the driving force will be proportional to total charge of a block and therefore its area . ) plugging these results into equation @xmath72 , we find that the prediction @xmath73 = @xmath74 becomes @xmath75 or @xmath76.@xcite if this relationship correctly describes the crossover to fast growth , then simulations with a well - developed @xmath77 growth before crossover should follow the scaling collapse @xmath78 , at least until fast growth has taken over . figure [ crosscollapse ] shows such a collapse . considering the numerical difficulty of achieving well - developed @xmath2 growth for a wide range of fields , we believe an @xmath79 crossover is supported by the data ; in any case , our results strongly indicate that length scale at crossover varies only weakly with field . thus , in our model , a reduction in external field only produces a small increase in the minimum domain size for takeoff . although the departure from @xmath2 growth appears to be small at low fillings , the field driven takeoff at higher fillings soon leads to large empty regions which move steadily against the field as particles sweep quickly through their centers . for moderately high lattice fillings , fast growth involves most of the vacancy regions . here , domain growth is very roughly linear in time , and horizontal correlations come close to scaling . at very high lattice fillings and low temperatures , fewer domains undergo significant coarsening , but those that do have runaway , exponential growth . in our model , explosive growth ends when domains are large enough to have rough bases , either through thermal effects or constant collisions . our study has also explored the strong impact which faceting can have on size dependence in velocities of vacancy clusters . this is a subject with potential applications in the study of void electromigration in small aluminum interconnects , where faceting is well documented and voids have been observed to move through the middle of single crystal grains @xcite . most importantly , our model demonstrates that external driving forces can be surprisingly effective in producing domain clumping and macroscopic particle fluxes . how such enhancement plays out in particular experimental systems is still an open question . in the instance of moeckly s ybco electromigration experiments , particle motion takes place in the anisotropic environment of the oxygen `` chain '' planes , and our simple model does not incorporate such inherent anisotropies . also , associating our model with the ybco experiment involves abstracting our simulated phase separation of completely filled and empty areas to an experimental phase separation which may be less extreme . neutron and tem observations of ybco suggest that domain segregation in these planes produces regions of more closely spaced oxygen rows and less closely spaced rows@xcite . still , the more open environment of widely spaced rows does allow increased mobility@xcite . moeckly s observations of large oxygen - depleted regions suggest that field - induced clumping is vital component of his experiments . without describing the specific characteristics of ybco , our model provides a qualitative check that small external driving forces can indeed facilitate the segregation of domains with high particle mobility . this study serves as a preliminary survey of a broad range of interesting and potentially relevant model behaviors . an extension to three dimensions would allow us to study the effect of a finite - temperature roughening transition . our study of faceting effects should be expanded to cover other types of dynamics , such as those which facilitate surface diffusion . our simple picture of coarsening in the presence of scaling clearly needs to be modified to include departures from scaling and fluctuations in domain velocity . and an entire regime of low filling needs to be explored and understood . our work illustrates the breadth of issues involved in studying how a separation of time - scales due to faceting can affect response to an external driving force . we have demonstrated that useful approaches to this problem may be found outside the long wavelength , late time limit . further work should improve our understanding of particle motion and domain coarsening in systems which , instead of being conveniently isolated in a thermal bath , are knocked out of equilibrium by an external force . we would like to thank b. moeckly , r. buhrman , j. marko , and g. barkema for helpful conversations . this work was partly funded by the npsc ( lkw ) , and the nsf under grant dmr9118065 ( lkw , jps ) . this research was conducted using the resources of the cornell theory center , which receives major funding from the national science foundation ( nsf ) and new york state . additional funding comes from the advanced research projects agency ( arpa ) , the national institutes of health ( nih ) , ibm corporation , and other members of the center s corporate research institute . ( roughly 1000 ibm sp1 processor hours were used . ) j. d. gunton , m. san miguel , and p. s. sahni , in _ phase transitions and critical phenomena _ , vol . 8 , eds . c. domb and j. l. lebowitz ( academic , new york , 1983 ) p. 267 . for a more recent review , see a. j. bray , adv . , to be published . two processes tend to make domains fatter . they can combine sideways with other domains , and the column of atoms at the side of a domain can come loose and be swept up to the top of the domain by the field . widening continues until these processes are balanced by the rate at which pile - ups of atoms at the top corners of a domain can grow to refill a side column of particles . note that this procedure only gives a precise measure of length scale in a scaling regime , where the basic shape of the correlation function remains constant . in the present regime , the outer tail of the correlation curve grew slightly more quickly than the midsection . note that if domains are rough and @xmath65 is independent of @xmath63 , we expect @xmath80 . this still gives @xmath81 . see gunton s article in@xcite for a discussion of various diffusion mechanisms for rough domains . r. j. cava , _ et al . _ , physica c , * 165 * , 419 ( 1990 ) . s. amelinckx , g. van tendeloo , and j. van landuyt , solid state ionics , * 39 * , 37 ( 1990 ) . j. reyes - gasga , t. krekels , g. van tendeloo , _ et al . _ , physica c , * 159 * , 831 ( 1989 ) .
we study electromigration in a driven diffusive lattice gas ( ddlg ) whose continuous monte carlo dynamics generate higher particle mobility in areas with lower particle density . at low vacancy concentrations and low temperatures , vacancy domains tend to be faceted : the external driving force causes large domains to move much more quickly than small ones , producing exponential domain growth . at higher vacancy concentrations and temperatures , even small domains have rough boundaries : velocity differences between domains are smaller , and modest simulation times produce an average domain length scale which roughly follows @xmath0 , where @xmath1 varies from roughly .55 at 50% filling to roughly .75 at 70% filling . this growth is faster than the @xmath2 behavior of a standard conserved order parameter ising model . some runs may be approaching a scaling regime . a simple scaling picture which neglects velocity fluctuations , but includes the cluster size dependence of the velocity , predicts growth with @xmath3 . at low fields and early times , fast growth is delayed until the characteristic domain size reaches a crossover length which follows @xmath4 . rough numerical estimates give @xmath5 and simple theoretical arguments give @xmath6 . our conclusion that small driving forces can significantly enhance coarsening may be relevant to the yb@xmath7cu@xmath8o@xmath9 electromigration experiments of moeckly _ et al._@xcite .
SECTION 1. SHORT TITLE. This Act may be cited as the ``Educational Empowerment Act''. SEC. 2. DESIGNATION OF EDUCATIONAL EMPOWERMENT ZONES. (a) In General.--Chapter 1 of the Internal Revenue Code of 1986 is amended by adding at the end the following new subchapter: ``Subchapter X--Educational Empowerment Zones ``Sec. 1400E. Designation of educational empowerment zones. ``SEC. 1400E. DESIGNATION OF EDUCATIONAL EMPOWERMENT ZONES. ``(a) Designation.-- ``(1) Educational empowerment zone.--For purposes of this title, the term `educational empowerment zone' means any area-- ``(A) which is nominated by one or more local governments and the State or States in which it is located for designation as an educational empowerment zone (hereinafter in this section referred to as a `nominated area'), and ``(B) which the Secretary of Health and Human Services and the Secretary of Education (hereinafter in this section referred to as the `Secretaries concerned') jointly designate as an educational empowerment zone. ``(2) Number of designations.--The Secretaries concerned may designate not more than 30 nominated areas as educational empowerment zones. ``(3) Areas designated based on degree of poverty, etc.-- Except as otherwise provided in this section, the nominated areas designated as educational empowerment zones under this subsection shall be those nominated areas with the highest average ranking with respect to the criteria described in subsection (c)(3). For purposes of the preceding sentence, an area shall be ranked within each such criterion on the basis of the amount by which the area exceeds such criterion, with the area which exceeds such criterion by the greatest amount given the highest ranking. ``(4) Limitation on designations.-- ``(A) Publication of regulations.--The Secretaries concerned shall prescribe by regulation no later than 4 months after the date of the enactment of this section-- ``(i) the procedures for nominating an area under paragraph (1)(A). ``(ii) the parameters relating to the size and population characteristics of an educational empowerment zone, and ``(iii) the manner in which nominated areas will be evaluated based on the criteria specified in subsection (c). ``(B) Time limitations.--The Secretaries concerned may designate nominated areas as educational empowerment zones only during the 24-month period beginning on the first day of the first month following the month in which the regulations described in subparagraph (A) are prescribed. ``(C) Procedural rules.--The Secretaries concerned shall not make any designation of a nominated area as an educational empowerment zone under paragraph (2) unless-- ``(i) a nomination regarding such area is submitted in such a manner and in such form, and contains such information, as the Secretaries concerned shall by regulation prescribe, and ``(ii) the Secretaries concerned determine that any information furnished is reasonably accurate. ``(5) Nomination process for indian reservations.--For purposes of this subchapter, in the case of a nominated area on an Indian reservation, the reservation governing body (as determined by the Secretary of the Interior) shall be treated as being both the State and local governments with respect to such area. ``(b) Period for Which Designation is in Effect.--Any designation of an area as an educational empowerment zone shall remain in effect during the period beginning on the date of the designation and ending on the earliest of-- ``(1) December 31, 2007, ``(2) the termination date designated by the State and local governments in their nomination, or ``(3) the date the Secretaries concerned revoke such designation. ``(c) Area and Eligibility Requirements.-- ``(1) In general.--The Secretary of Commerce may designate a nominated area as an educational empowerment zone under subsection (a) only if the area meets the requirements of paragraphs (2) and (3) of this subsection. ``(2) Area requirements.--For purposes of paragraph (1), a nominated area meets the requirements of this paragraph if-- ``(A) the area is within the jurisdiction of one or more local governments, ``(B) the boundary of the area is continuous, and ``(C) the area does not include an empowerment zone (as defined in section 1393(b)) other than such a zone designated under section 1391(g). ``(3) Eligibility requirements.--For purposes of paragraph (1), a nominated area meets the requirements of this paragraph if the State and the local governments in which it is located certify that the nominated area satisfies such conditions as the Secretary of Education deems appropriate. ``(4) Consideration of dropout rate, etc.--The Secretary of Education, in setting forth the conditions for eligibility pursuant to paragraph (3), shall take into account the extent to which an area has low-income families, a high dropout rate, a high rate of teen pregnancy, and large school class size. ``(d) Coordination With Treatment of Enterprise Communities.--For purposes of this title, if there are in effect with respect to the same area both-- ``(1) a designation as an educational empowerment zone, and ``(2) a designation as an enterprise community, both of such designations shall be given full effect with respect to such area. ``(e) Definitions and Special Rules.--For purposes of this subchapter, rules similar to the rules of paragraphs (2), (3), (5), and (7) of section 1393 shall apply.''. (b) Clerical Amendment.--The table of subchapters for chapter 1 is amended by adding at the end the following new item: ``Subchapter X. Educational Empowerment Zones.''. SEC. 3. CREDIT FOR DONATIONS TO SCHOOL DISTRICTS IN EDUCATIONAL EMPOWERMENT ZONES. (a) In General.--Subpart B of part IV of subchapter A of chapter 1 of the Internal Revenue Code of 1986 is amended by inserting after section 30A the following new section ``SEC. 30B. CONTRIBUTIONS TO SCHOOL DISTRICTS IN EDUCATIONAL EMPOWERMENT ZONES. ``(a) Allowance of Credit.--There shall be allowed as a credit against the tax imposed by this chapter for the taxable year an amount equal to the amount of qualified educational empowerment zone contributions made by the taxpayer during such year. ``(b) Maximum Credit.--The amount of the credit allowed by subsection (a)-- ``(1) in the case of an individual, shall not exceed $2,000, and ``(2) in the case of any other taxpayer, shall not exceed $10,000. ``(c) Definition of Qualified Educational Empowerment Zone Contributions.--For purposes of this section, the term `qualified educational empowerment zone contributions' means cash contributions made to any school district located in an educational empowerment zone (as designated under section 1400E) if such contributions-- ``(1) but for subsection (d), would be allowable as a deduction under section 170, and ``(2) are used for any of the following purposes by the school district: ``(A) Hiring new teachers. ``(B) Increasing teacher salaries. ``(C) Training teachers. ``(d) Denial of Double Benefit.--No deduction shall be allowed under this chapter for any contribution taken into account in computing the credit under this section. ``(e) Election.--This section shall apply to any taxpayer for any taxable year only if such taxpayer elects (at such time and in such manner as the Secretary may by regulations prescribe) to have this section apply for such taxable year. ``(f) Application With Other Credits; Carryover of Excess Credit.-- The credit allowed by subsection (a) for any taxable year shall not exceed the excess (if any) of-- ``(1) the regular tax for the taxable year reduced by the sum of the credits allowable under subpart A and the preceding sections of this subpart, over ``(2) the tentative minimum tax for the taxable year. If the credit under subsection (a) exceeds the limitation of the preceding sentence, such excess shall be added to the credit allowable under subsection (a) for the succeeding taxable year.''. (b) Clerical Amendment.--The table of sections for subpart B of part IV of subchapter A of chapter 1 of such Code is amended by inserting after the item relating to section 30A the following new item: ``Sec. 30B. Contributions to school districts in educational empowerment zones.''. (c) Effective Date.--The amendments made by this section shall apply to taxable years beginning after December 31, 2003. SEC. 4. TEACHER LOAN FORGIVENESS PROGRAM. Part B of title IV of the Higher Education Act of 1965 is amended by inserting after section 428K (20 U.S.C. 1078-11) the following new section: ``SEC. 428L. LOAN FORGIVENESS FOR MATHEMATICS AND SCIENCE TEACHERS. ``(a) Purpose.--It is the purpose of this section to encourage more individuals to enter and stay in the field of teaching mathematics, science, and related fields. ``(b) Program.-- ``(1) In general.--The Secretary shall carry out a program of assuming the obligation to repay, pursuant to subsection (c), a loan made, insured, or guaranteed under this part or part D (excluding loans made under sections 428B and 428C or comparable loans made under Part D) for any new borrower after October 12, 1998, who-- ``(A) has been employed as a full-time teacher for 3 consecutive complete school years in a school that is located in an educational empowerment zone, as such term is defined in section 1400E of the Internal Revenue Code of 1986; ``(B) is a fully qualified teacher; and ``C) is not in default on a loan for which the borrower seeks forgiveness. ``(2) Award basis; priority.-- ``(A) Award basis.--Subject to subparagraph (B), loan repayment under this section shall be on a first- come, first-served basis and subject to the availability of appropriations. ``(B) Priority.--The Secretary shall give priority in providing loan repayment under this section for a fiscal year to student borrowers who received loan repayment under this section for the preceding fiscal year. ``(3) Regulations.--The Secretary is authorized to prescribe such regulations as may be necessary to carry out the provisions of this section. ``(c) Loan Repayment.-- ``(1) Eligible amount.--The amount the Secretary may repay on behalf of any individual under this section shall not exceed-- ``(A) 80 percent of the sum of the principal amounts outstanding of the individual's qualifying loans at the end of 3 consecutive complete school years of service described in subsection (b)(1)(A); ``(B) an additional 10 percent of such sum at the end of each of the next 2 consecutive complete school years of such service; and ``(C) a total of more than $10,000. ``(2) Construction.--Nothing in this section shall be construed to authorize the refunding of any repayment of a loan made under this part or part D. ``(3) Interest.--If a portion of a loan is repaid by the Secretary under this section for any year, the proportionate amount of interest on such loan which accrues for such year shall be repaid by the Secretary. ``(4) Double benefits prohibited.--No borrower may, for the same service, receive a benefit under both this section and subtitle D of title I of the National and Community Service Act of 1990 (42 U.S.C. 12601 et seq.). No borrower may receive a reduction of loan obligations under both this section and section 428J or 460. ``(d) Repayment to Eligible Lenders.--The Secretary shall pay to each eligible lender or holder for each fiscal year an amount equal to the aggregate amount of loans which are subject to repayment pursuant to this section for such year. ``(e) Application for Repayment.-- ``(1) In general.--Each eligible individual desiring loan repayment under this section shall submit a complete and accurate application to the Secretary at such time, in such manner, and containing such information as the Secretary may require. ``(2) Conditions.--An eligible individual may apply for loan repayment under this section after completing the required number of years of qualifying employment. ``(3) Fully qualified teachers.--An application for loan repayment under this section shall include such information as is necessary to demonstrate that the applicant-- ``(A) if teaching in a public elementary or secondary school (other than as a teacher in a public charter school), has obtained State certification as a teacher (including certification obtained through alternative routes to certification) or passed the State teacher licensing exam and holds a license to teach in such State; and ``(B) if teaching in-- ``(i) an elementary school, holds a bachelor's degree and demonstrates knowledge and teaching skills in reading, writing, mathematics, science, and other areas of the elementary school curriculum; or ``(ii) a middle or secondary school, holds a bachelor's degree and demonstrates a high level of competency in all subject areas in which he or she teaches through-- ``(I) a high level of performance on a rigorous State or local academic subject areas test; or ``(II) completion of an academic major in each of the subject areas in which he or she provides instruction. ``(f) Evaluation.-- ``(1) In general.--The Secretary shall conduct, by grant or contract, an independent national evaluation of the impact of the program assisted under this section. ``(2) Competitive basis.--The grant or contract described in subsection (b) shall be awarded on a competitive basis. ``(3) Contents.--The evaluation described in this subsection shall-- ``(A) determine the number of individuals who were encouraged by the program assisted under this section to pursue teaching careers; ``(B) determine the number of individuals who remain employed in teaching mathematics, science, or related fields as a result of participation in the program; ``(C) identify the barriers to the effectiveness of the program; ``(D) assess the cost-effectiveness of the program; and ``(E) identify the number of years each individual participates in the program. ``(4) Interim and final evaluation reports.--The Secretary shall prepare and submit to the President and the Congress such interim reports regarding the evaluation described in this subsection as the Secretary deems appropriate, and shall prepare and so submit a final report regarding the evaluation by January 1, 2006''.
Educational Empowerment Act - Amends the Internal Revenue Code to allow a tax credit for qualified educational empowerment zone contributions. Allows the designation of up to 30 such zones. Bases designations on the degree of poverty.Establishes a teacher loan forgiveness program for mathematics and science teachers.
with increase in energies of accelerators , accurate data on high - multiplicity events at high energies have recently been provided . this makes it possible to analyze correlations and fluctuations such as the bose - einstein correlations ( bec)@xcite and the intermittency @xcite in detail . these correlations and fluctuations of produced particles are rather new tools to study multiparticle production . by analyzing them , one may be able to extract useful information on the space - time size of the particle production region and the production mechanism@xcite . correlations and fluctuations may also provide a clear signal of quark gluon plasma formation expected in high energy nucleus - nucleus collisions . on the other hand , multiparticle production is a phenomenon observed commonly in various reactions such as @xmath0 annihilations , lepton - hadron deep inelastic interactions , hadron - hadron interactions , and nucleus - nucleus collisions . a large amount of correlation data has been accumulated on various reactions . it has been found that there are some universal characteristics which are independent of the reaction type while some other properties depend on it . phenomenological models which can describe some crucial properties of many particle correlations will be very useful for systematic investigations of those characteristics caused by correlations and fluctuations . the bec have lately attracted considerable attention , in particular , because they may give information on the space time structure of hadronic source and they may cause large fluctuations of particle density in the phase space . although many existing phenomenological models have not taken into account the bec completely yet , there are some models ( or event generators ) which allow computing the two identical particle correlation functions . in most cases , the bec are generated more or less artificially . for example , they are calculated by using ( i ) the fourier transformation of the model s source function@xcite or ( ii ) the wigner function@xcite , ( iii ) by weighting every event@xcite , or ( iv ) by modifying the distribution of momentum difference of identical particle pairs in each event@xcite . however , some of those models can not describe the bec in a single event . motivated by those consideration , we would like to propose a new statistical model . it is constructed by the maximum entropy method @xcite and two versions of the model , the @xmath3-model and the @xmath2-model are applied to @xmath0 annihilation in this paper . the most characteristic point of our model is that the bec is taken into account in quantum statistical level with a characteristic correlation length ( @xmath1 ) defined in the rapidity space . this paper is organized as follows . in sec.i@xmath4i , our model is explained and the distribution functions of the final state hadrons are derived . sec.i@xmath4i@xmath4i is devoted to the explanation of the simulation method including the procedure of parameter determination . comparison of results obtained from simulation with the experimental data from petra to lep energies is given in sec.i@xmath4v . concluding remarks and discussions are given in sec.v . we first consider the @xmath3-model , i.e. , we assume that only pions are produced according to a statistical distribution . a system consisting of many pions produced in a single event may be decomposed into three subsystems , which consist of like sign pions , that is , @xmath5 , @xmath6 and @xmath7 subsystems . for example , consider a @xmath8 subsystem in the longitudinal phase space with limited transverse momentum@xcite . the longitudinal axis may be identified with the direction of the initial quark and antiquark produced by the virtual photon in center of mass system . then the rapidity space in the longitudinal phase space is divided into many cells @xcite of equal size @xmath1 , and we consider a probability to find @xmath8 mesons in each cell . the probability of finding @xmath9 @xmath8s in the _ i_-th cell , @xmath10 is normalized as @xmath11 the summation index @xmath9 runs from 0 to infinity because of the bose - einstein statistics . the mean @xmath8 multiplicity and the mean energy of the @xmath8 subsystem are given , respectively , by : @xmath12 and @xmath13 here @xmath14 is the energy of a @xmath8 in the _ i_-th cell : @xmath15 , \end{aligned}\ ] ] where @xmath16 is the central rapidity value of the _ i_-th cell , @xmath17 is the kinematical minimum value of rapidity , @xmath18 is the mean transverse mass , and @xmath19 is the total center of mass energy . the same argument applies to both @xmath20 and @xmath21 subsystems . therefore the mean multiplicities and the mean energies of those subsystems are given as @xmath22 and @xmath23 where @xmath24 is the mean charged multiplicity . the most probable distribution @xmath10 for the @xmath8 subsystem can be determined by the maximum entropy method which is well - known in information theory@xcite . according to a statistical picture , particles will distribute in the phase space in such a way that every possible state is realized with the same probability . this method has been applied in many fields in science including multiparticle production phenomenology . first , we define the missing information entropy @xcite : @xmath25 this @xmath26 has the maximum value when @xmath10 is a constant , so - called equal _ a priori _ probabilities , which does not depend on @xmath27 and @xmath9 . it is noted here that the probability @xmath10 does not depend on @xmath28 when ( @xmath29 ) . therefore a probability of finding @xmath9 @xmath8s in the @xmath27-th cell and @xmath30 @xmath8s in the @xmath31-th cell simultaneously , @xmath32 , is given by @xmath33 the entropy @xmath26 should be maximized with the constraints which correspond to the normalization eq.([nor ] ) , the mean multiplicity eq.([mul ] ) and the mean energy eq.([ene ] ) of the subsystems . for that purpose we consider @xmath34 defined below instead of @xmath26 by introducing lagrange multipliers @xmath35 , @xmath36 and @xmath37 ; @xmath38 by requiring that the variation of @xmath34 is vanishing , one obtains @xmath39 here , the lagrange multipliers @xmath40 and @xmath41 are rewritten in terms of the partition function @xmath42 , the `` partition '' temperature @xmath43 @xcite and the `` chemical '' potential @xmath44 : @xmath45 @xmath46 @xmath47 the parameters @xmath43 and @xmath44 are determined uniquely for given @xmath48 and @xmath49 and they play a dominant role to reproduce the gross features of data on single particle spectra . the probability distribution functions for @xmath20 and @xmath21 subsystems are the same as @xmath10 for @xmath8 subsystem . the parameter @xmath1 is determined by fitting to data on the second order fluctuations of multiplicity . in order to study the resonance effect , we also consider another extreme case called @xmath2-model where it is assumed that only @xmath2 mesons are produced in the same way as pions in the @xmath3-model . in the @xmath2-model , one must take the spin degree of freedom into account . a @xmath2 meson system is decomposed into nine subsystems : @xmath50 , @xmath51 , @xmath52 , @xmath53 , @xmath54 , @xmath55 , @xmath56 , @xmath57 , and @xmath58 , where @xmath59 , and @xmath60 denote the three eigenstates of the spin @xmath61 + 1 , 0 and -1 , respectively . the partition temperature @xmath62 , the `` chemical potential '' @xmath63 and the cell size @xmath64 in the @xmath2-model are determined so as to reproduce the mean charged multiplicity , the total energy and the second order fluctuations of multiplicity . ( the decay process of @xmath2 meson will be discussed in sec.i@xmath4i@xmath4i b ) the method of generating events based on the @xmath3-model and the @xmath2-model is explained in this section . events generating procedures are divided into three steps . the first step is determination of the parameters @xmath44 and @xmath43 . the second step is @xmath1 search with trial events . by using these determined parameters , the final simulations are executed in the third step . * step 1 : determination of the parameters @xmath44 and @xmath43 * to determine the values of @xmath43 and @xmath44 , we solve the following simultaneous equations for @xmath44 and @xmath43 with a fixed trial value of @xmath1 : @xmath65 @xmath66 where observed value is used for the mean charged multiplicity @xmath24 . it should be noted here that @xmath44 and @xmath43 are determined as functions of @xmath1 , i.e. @xmath67 , @xmath68 . + * step 2 : generation of trial events and determination of the parameter @xmath1 * 1 . in order to avoid a possible artifact due to a particular cell location , we now take the central value @xmath16 of the @xmath27-th cell as @xmath69 , where @xmath70 is a homogeneous random number between 0 and 1 . 2 . the @xmath8 , @xmath21 and @xmath20 subsystems are generated in all cells in the rapidity space according to the probability distribution @xmath10 with a trial @xmath1 , @xmath71 and @xmath72 . when a pion is produced in a certain cell , its rapidity is assigned by using a random number so that pions distribute homogeneously in that cell . this smearing of pion rapidity causes slight changes of @xmath24 and @xmath73 in comparison with the result of the step 1 . we readjust the values of @xmath74 and @xmath43 to reproduce correctly the mean multiplicity and the `` mean '' energy of the system . 3 . charge conservation is demanded event by event . events are discarded if the charge conservation is violated . the transverse momenta are generated according to the following distribution : @xmath75 here @xmath76 denotes the observed mean transverse momentum at each @xmath73 . + the azimuthal angle @xmath77 of the transverse momentum is distributed at random between 0 and 2@xmath3 . the transverse momenta generated in this way are assigned to all pions independent of their rapidities . a four momentum of a pion is then given as @xmath78 5 . approximate energy - momentum conservation is also required . for energy conservation , we set an energy window with width @xmath79 around @xmath73 . for momentum conservation , we also set the longitudinal and the transverse momentum windows with widths @xmath80and @xmath81 , respectively , around @xmath82 total momentum . the total energy @xmath83 , the longitudinal component of the total momentum @xmath84 and the transverse component @xmath85 are evaluated in every event . an event is adopted only when it satisfies the inequalities @xmath86 and @xmath87 @xmath88 as an example , the distribution of @xmath83 and the applied energy window for @xmath73=34.5 gev are shown in fig.1 . one has to take the window size as small as possible to keep the quality of conservation law while one would like to take it as large as possible to save the computation time . thus one has to determine an optimum value of window size . we decided to take @xmath89 and @xmath90 , where @xmath91 is the maximum value of the c.m . momentum carried by a pion . by the way , we found that some physical quantities , e.g. , the dispersion of the multiplicity distributions are rather sensitive to @xmath92 when @xmath92 is large . we have confirmed that this strong @xmath92-dependence disappears when @xmath89 , which implies that the physical observables are insensitive to @xmath92 if @xmath93 . for @xmath94-conservation , we use a multiplicity dependent window size @xmath95 . the jet axis , thrust or sphericity , is determined event by event . new four components of a momentum vector of a pion are calculated by referring to this jet axis . the value of the parameter @xmath1 is determined by fitting to appropriate experimental data which are sensitive to @xmath1 . we have used the rapidity interval dependence of @xmath96 for the fitting . here , @xmath97 . + * figure 1 . + * step 3 : final event generation * a sufficiently large number of events are generated using the probability distribution @xmath98 with @xmath44 , @xmath43 and @xmath1 determined in the preceding steps . final results of those parameters are shown in table i and the results of the fitting are shown in fig.2(a)-(c ) , where @xmath99 is the half size of the rapidity interval @xmath100 $ ] . experimental data are taken from refs.@xcite . as shown in table i , 0.6 , 0.8 and 1.2 are chosen as the values of the @xmath1 at @xmath101 14.0 , 34.5 and 91.2 gev , respectively . in the determination of the best fit value @xmath1 , we have put a special weight on the data point for @xmath99 = @xmath102 in order to reproduce the multiplicity distribution for full phase space as precisely as possible . it should be noted that @xmath99 dependence of the @xmath103 , a kind of 2nd order fluctuations of the particle density in the rapidity space , is reproduced well . + * figure 2 . ( a)-(c ) * + * table i * + + the parameter @xmath62 , @xmath63 and @xmath64 in the @xmath2-model are determined in a way similar to the @xmath3- model . the results are given in table i@xmath4i . + * table i@xmath4i * + + now we discuss the decay of @xmath2 mesons e.g. @xmath104 . rapidities have to be assigned to each pion produced from one @xmath2 meson of some rapidity @xmath105 . in the rest frame of the @xmath2 meson , the maximum and the minimum rapidities of the two pions produced by the @xmath2 meson are given by @xmath106 where @xmath107 and @xmath108 and @xmath109 are the masses of the @xmath2 and @xmath3 mesons . we use the following breit - wiger form @xmath110 as the invariant mass distribution of @xmath2 meson : @xmath111 where @xmath112=770 mev and @xmath113=150 mev . to impose the bose - einstein correlations between like charge pions , we use an `` enhancement factor '' method . when a parent @xmath2 meson has a rapidity @xmath105 , we divide the longitudinal rapidity interval @xmath114 $ ] into @xmath115 cells of equal size @xmath116 . here we take @xmath117 . in order to determine the cell to which a pion , say @xmath8 , belongs , we introduce the enhancement factor : @xmath118 where @xmath119 and @xmath120 are the number of @xmath8s already produced in the @xmath27-th cell and that in the interval @xmath114 $ ] , respectively . transverse momenta @xmath121 and @xmath122 are assigned to the two pions , in the same way as in the @xmath3- model . to reproduce the invariant mass of the parent @xmath2 meson @xmath108 , the azimuthal angle difference , @xmath123 , needs to satisfy the following equation : @xmath124 in this chapter we compare the results of event simulation with experimental data . we investigate effects of charge and energy - momentum conservations and also the resonance effect by comparing the results from @xmath3- and @xmath2- models . 20000 events of multiparticle production in @xmath0 annihilation have been generated for both the @xmath3-model and the @xmath2-model at each energy @xmath125 and @xmath126 gev . we use the experimental data reported by the tasso collaboration@xcite for @xmath127 gev , and by the delphi @xcite and aleph collaborations@xcite for @xmath126 gev . we present all results obtained from the @xmath3-model . when significant differences are found between the two models , we present also the result of the @xmath2- model . charged multiplicity distributions @xmath128 are shown in figs.3 ( a)-(c ) . the experimental data@xcite are well reproduced by our @xmath3-model . this is reasonable because the mean multiplicity and dispersion of the multiplicity distribution are used in the determination of the model parameters . it should be noted , however , that our model is able to predict the detailed shape of the multiplicity distribution at each energy . we also investigate the multiplicity distribution in terms of kno variable . our model gives good scaling behavior for both the full phase space(see fig.4(a ) ) and small rapidity windows(not shown ) . the @xmath99-dependence of the multiplicity distribution is reproduced correctly as shown in fig.4(b ) . note that our results are approximately consistent with the negative binomial distributions . + * figure 3 . ( a)-(c ) * + * figure 4 . ( a ) and ( b ) * + + dependence of multiplicity distributions on @xmath1 has already been demonstrated in figs.2(a)-(c ) . decreasing @xmath1 reduces the dispersion of the multiplicity distribution . conservation laws also affect the multiplicity distribution . in addition to `` full conservation '' event for which both energy - momentum and charge conservation are imposed , we have also generated events with `` only charge conservation '' , `` only energy - momentum conservation '' or `` no conservation '' by imposing only charge conservation or only energy - momentum conservation or none of them in order to investigate the effects of conservation laws . it is found that the charge conservation causes the broadening of the multiplicity distribution , while the effect of energy conservation is opposite as shown in fig.5 . the effect of energy - momentum conservation is stronger than that of charge conservation . we have investigated the charge correlations due to charge conservation . for this purpose , we consider the rapidity window dependence of the quantity @xmath129 , where @xmath130 is the dispersion of the @xmath8 multiplicity distribution , @xmath131 . the quantity @xmath129 can be written as @xmath132 where use was made of the equality @xmath133 . if there is the maximum correlation @xmath134 due to charge conservation , one has @xmath135 because @xmath136 . on the other hand , if there is no correlation between @xmath137 and @xmath138 , @xmath139 is reduced to @xmath140 and hence @xmath141 . therefore , it is obvious that @xmath135 for @xmath142 . on the other hand , one can expect that @xmath141 for very small @xmath99 because the correlation due to charge conservation will be maximally weakened when @xmath99 is small . those expectations are indeed realized by our simulation as shown in fig.6 . the correlation measure @xmath129 increases linearly from about unity as @xmath99 increases and then tends to saturate at the value 2 for @xmath1433.5 . the slope of the linear rise may be regarded as a measure of local charge conservation . unfortunately , it appears that corresponding experimental data are not available at present . we therefore urge experimentalists to provide such data . + * figure 5 * + * figure 6 ( a ) and ( b ) * + + the single particle rapidity distributions are calculated and the results are shown in fig.7 . our model reproduces the experimental data@xcite except for the observed dip structure at @xmath144=14.0 and 34.5 gev , because integration of the @xmath145 data reported by tasso is smaller than the reported mean multiplicity . ] . in particular , the energy dependence of the central height is reproduced correctly by our model . although our model produces a dip at @xmath146=0 in qualitative agreement with experimental data , it is too deep and too narrow . furthermore it tends to diminish as @xmath73 increases . this tendency appears opposite to what is observed experimentally . this situation does not change even if one uses the @xmath2- model . the discrepancy may be due to the fact that three jet events are not included in our model . by the way , we found that the dip is not reproduced if one uses the sphericity instead of the thrust to define the jet axis . we have also confirmed that the rapidity distribution is insensitive to both conservation laws and the value of @xmath1 . + * figure 7 . * + + there are interesting experimental data on the rapidity dependence of the mean transverse momentum , @xmath147@xcite . the observed @xmath147 is almost constant in the central region while it decreases as @xmath146 approaches the kinematical limit as shown in fig.8(a ) . on the other hand , transverse momentum of a pion is generated according to the exponential formula ( 18 ) with @xmath146-independent mean transverse momentum @xmath148 in our model . therefore , it is very interesting to see if our model can reproduce the observed @xmath146-dependence of the mean transverse momentum . the result of our model is shown and compared with data in fig.8(a ) . our model reproduces correctly the observed @xmath146-dependence of the mean transverse momentum . therefore , one can conclude that the observed @xmath146-dependence is totally due to kinematical reasons . to confirm this conclusion , we have calculated @xmath147 for events generated without energy - momentum conservation and/or without assigning the thrust axis . the result for 34.5 gev is shown in fig . it is clearly seen that the energy - momentum conservation is most responsible for reproducing the correct @xmath146-dependence but the use of thrust axis has also some effect . + * figure 8 . ( a ) and ( b ) * + + we study the scaled factorial moments in order to investigate the fluctuations of particle density in the rapidity space . the following two kinds of scaled factorial moment are used for comparison with experimental data . the factorial moments are evaluated for the multiplicity of particles produced in the rapidity window @xmath149 . the rapidity window is divided into m bins of equal size @xmath150 . when @xmath151 particles are produced in the window while @xmath152 particles are found in the @xmath153-th bin , the ` exclusive ' scaled factorial moment@xcite is defined as @xmath154 where @xmath155 means an event average with fixed @xmath151 . the ` inclusive ' scaled factorial moment used in many literatures@xcite is given by @xmath156 where @xmath155 now means an event average for distributed @xmath151 . both @xmath157 and @xmath158 are equal to unity if there are only statistical fluctuations ( a binomial distribution for @xmath157 or a poisson distribution for @xmath158 ) . on the other hand , the bose - einstein distribution ( eq.(12 ) ) gives a typical example of non - statistical fluctuations . it is the multiplicity distribution in a single cell of size @xmath1 in our model , corresponding to @xmath159 . in this case the inclusive factorial moments of the second order for like charged and all charged particles are given , respectively , by @xmath160 and @xmath161 for @xmath73=34.5gev , one can investigate the fluctuations in a single cell , i.e. fluctuations induced by pure bose - einstein distributions(cf . eq ( [ fac - es ] ) ) at @xmath162=5 since @xmath1=0.8 and @xmath163=4.0 . our simulation gives @xmath164 1.27 , and @xmath165 1.38 . the reduction from 1.5 can be attributed to the smearing due to varying cell location(cf . the item 1 of the step 2 of sec.i@xmath4i@xmath4i a ) and also to the global charge conservation . in fact , we obtain @xmath1661.32 , and @xmath167 1.46 when all the conservation laws are not imposed . now the results are compared with experimental data@xcite for both exclusive and inclusive factorial moments in figs . 9 and 10 . our results approximately reproduce the experimental data . in particular , the agreement is very good for @xmath168 gev . in our model , the parameter @xmath1 plays a crucial role in reproducing the bin size dependence of the factorial moments . as @xmath162 increases from unity , the factorial moments increase due to the bec and then start to saturate for @xmath169 34.5 gev ) with results of various event simulators of multiparticle production model : webber , hoyer and lund model version 6.2 and 6.3 ( see refs in @xcite ) . those models can also roughly reproduce the experimental data . the bec are not taken into account while cascade processes are included in them . ] . in this sense , the parameter @xmath1 in our model may be interpreted as an effective correlation length in the rapidity space due to the bec . our results show that the bec considerably contribute to the increase of the scaled factorial moments(the so - called intermittency ) . however , at @xmath170 gev our results of both exclusive and inclusive factorial moment systematically underestimate compared with experimental data for all orders . this underestimation becomes remarkable as the order of the moment increases . it may be due to three jets events at high energy not taken into account in our calculation . at lep energy , events with three jets take place with a significant probability . - + * figure 9 . ( a)-(c ) * + * figure 10 . ( a)-(c ) * + + here the results for the bose - einstein correlation functions are compared with data at @xmath168@xcite , and @xmath126 gev @xcite . the following correlation functions @xmath171 ( or @xmath172 ) are used for this analysis : @xmath173 where @xmath174(or@xmath175 ) is the number of like sign pairs with four momentum difference : @xmath176 or @xmath177 . the so - called reference sample , the denominator @xmath178 is the number of pairs without bose - einstein correlations . tasso and aleph collaboration use the number of unlike sign pairs as @xmath178 . ` mixed pair reference ' is also used by aleph . in this case , a pair is taken from different events . our results of both the @xmath3- and the @xmath2- models are shown in figs . 11 and 12 , respectively . we also present energy dependence of the bec correlation function @xmath171 in figs.13(a ) for the @xmath3-model and ( b ) for the @xmath2-model . + * figure 11 . ( a),(b ) * + * figure 12 . * + + our model produces a characteristic enhancement of @xmath179 in small @xmath180 region . the result of the @xmath2-model is in better agreement with experimental data than the @xmath3-model for the whole region of @xmath181 . we found that the enhancement of the correlation function @xmath179 strongly depends on the size of @xmath1 . when @xmath1 becomes large , the slope of the correlation function becomes small . if @xmath1 is larger than the rapidity interval for the full phase space , i.e. @xmath182 , the correlation function has no @xmath183 dependence , @xmath184 . on the contrary when @xmath1 approaches to zero , the slope of the correlation function becomes large and @xmath171 approaches to unity for @xmath185 . although our model has no explicit information on the space - time structure of particle emission points , we can extract the size and the lifetime of the particle sources by fitting a theoretical formula to the result with mixed pair reference from our simulation . here we use the following fitting formula for @xmath1865 mev / c : @xmath187,\\ & & c(q^2)=~c[1+\lambda \exp(-r^2q^2 ) ] , \end{aligned}\ ] ] where @xmath188 is the normalization constant , @xmath189 is the so - called chaoticity parameter , and @xmath190 is the size parameter . we do nt use data for @xmath1915 mev / c in the fitting because the statistical errors are very large there . + * figure 13 . ( a ) and ( b)*. + + in table i@xmath4i@xmath4i , the results of the fitting at various energies are summarized for both the @xmath3-model and the @xmath2-model . with increasing energy of the system , @xmath190 decreases while @xmath189 tends to increase . we find that @xmath190 in the @xmath2-model is larger than that in the @xmath3-model . we also try to extract the longitudinal size @xmath192 , transverse size @xmath193 , and lifetime @xmath194 by using the following formulae in our fit : . @xmath195,\quad c(q_{{\mbox \scriptsize t}})= c_{{\mbox \scriptsize t}}[1+\lambda_{{\mbox \scriptsize t } } \exp(-r_{{\mbox \scriptsize t}}^2q_{{\mbox \scriptsize t}}^2)],\nonumber \\ & & c(\delta e)=c_{\tau}[1+\lambda_{\tau } \exp(-\tau^2\delta e^2 ) ] , \end{aligned}\ ] ] where @xmath196 . the results are presented in table i@xmath4v . the source size decreases with increasing @xmath73 , while the life time is almost independent of @xmath73 . it is reasonable that @xmath197 has no strong @xmath198-dependence because the bec is not taken into account in the transverse momentum space in our model . + * table i@xmath4i@xmath4i and i@xmath4v * + + the value of the normalization constant @xmath188 may be understood as follows . the number of unlike charged pairs and that of ( + + ) pairs for large @xmath183 may be proportional to ( statistical ) combinatorial numbers @xmath139 and @xmath199 , respectively . therefore the asymptotic value of the correlation function may be estimated as @xmath200 where we have used charge conservation in deriving the second line . ( [ bec - nor ] ) with the approximation @xmath201 and the experimental values of @xmath202 yields @xmath188=0.785 , 0.855 and 0.901 for @xmath73=14.0 , 34.5 and 91.2 gev , respectively in qualitative agreement with the result given in table i@xmath4i@xmath4i . we also investigate the influence of the charge and energy - momentum conservation on the bose - einstein correlations . both energy - momentum conservation and charge conservation reduce the values of the correlation functions in the whole @xmath183 ( or @xmath181 ) range as shown in fig.14 . the effect of charge conservation is stronger than that of energy - momentum conservation . if `` no conservation '' events are used , @xmath171 approaches to a larger constant as @xmath183 increases . + * figure 14 . * + + as mentioned in section i@xmath4i@xmath4i b , the bec in the @xmath2-model is imposed for like - charged pions by using the enhancement factor . by changing this enhancement factor , we can control the strength of the bec . for example , one can reduce the bec substantially by putting @xmath203 in eq.([enha ] ) as shown in fig.15 . + * figure 15 . * + + we investigate the 2-particle correlations in terms of rapidity variables in detail . the experimental data reported by tasso collaboration@xcite at @xmath73=34.5 gev is used in comparison with our calculations . when the 2-particles of type `` @xmath204 '' and `` @xmath205 '' ( for example , a , b = @xmath8 , @xmath20 ) have rapidities @xmath206 and @xmath207 , respectively , the two particle rapidity correlation function @xmath208 is defined as follows : @xmath209 where @xmath210 and @xmath211 is the two particle density and the one particle density , respectively : @xmath212 here @xmath213 is the total cross section and @xmath214 is the normalization constant given by @xmath215 where @xmath216 and @xmath217 and @xmath218 are the multiplicities of `` @xmath204 '' and `` @xmath205 '' , respectively . instead of using @xmath208 , in practical measurements by tasso collaboration , they use @xmath219 where @xmath220 refers to a rapidity interval ( @xmath221 , @xmath222 ) . these trigger rapidity intervals are trigger i ( -5.50@xmath223 y @xmath223 -2.50 ) , trigger i@xmath4i ( -2.50@xmath223 y @xmath223 -1.50 ) , trigger i@xmath4i@xmath4i ( -1.50@xmath223 y @xmath223 -0.75 ) and trigger i@xmath4v ( -0.75@xmath223 y @xmath223 -0.00 ) . first we investigate a case where sign of charge is not distinguished and hence @xmath224=0 . the results are compared with experimental data in fig.16(a)-(d ) . the experimental data are approximately reproduced by the simulation for every trigger regions . although our model predicts a negative correlation for large @xmath146 ( @xmath2252 ) in the trigger i , a positive correlation is reported by tasso . for the trigger regions i@xmath4i , i@xmath4i@xmath4i and i@xmath4v , calculated correlation functions show positive bumps around the trigger rapidity interval in agreement with experiment . the effect is apparently caused by the bec . + * figure 16(a)-(d ) * + + for confirmation , we calculate the 2-particle rapidity correlation @xmath226 and @xmath227 . see fig.17(a)-(d ) . the clear positive correlations are seen near the trigger rapidities in the correlation function @xmath228 . on the other hand , such positive correlations are absent in @xmath229 . from these investigations , one can conclude that the bec ( identical particle effect ) plays a crucial role in an enhancement of the @xmath226 near the trigger rapidity @xmath220 . the correlation functions are also affected by the effects of @xmath2 meson production and their decay . results of the @xmath2-model are shown in fig.18 . it is found that the @xmath2-model gives better agreement with experimental data than the @xmath3-model for all trigger rapidity intervals . + * figure 17 ( a)-(d ) * + + there are some discrepancies between the model result for @xmath230 and the data as most evidently seen in fig.16(a ) . the situation is qualitatively the same in both the @xmath3- and the @xmath2- models . this is an indication that there are unknown long range as well as short range correlations besides bec , e.g. those due to higher resonances and/or three jets . + * figure 18 . ( a)-(d ) * + + in analogy to @xmath171 , another 2-particle rapidity correlation function can be defined by using the rapidity deference @xmath231 in place of @xmath183 : @xmath232 this function allows us to measure the size of the model parameter @xmath1 . we expect that slope of @xmath233 will change at @xmath234 . in this paper , we assume that @xmath1 is independent of @xmath146 . this assumption can be checked by measuring @xmath233 in various rapidity regions . we strongly urge experimentalists to measure @xmath233 . our prediction for this correlation function is shown in fig.19(a)-(c ) . + * figure 19 . * + + finally we compare the results of the forward - backward correlation with experimental data@xcite . it is known experimentally that there are weak ( positive ) correlations between the multiplicity @xmath235 in the backward hemisphere and the mean multiplicity @xmath236 in the forward hemisphere . the direction of the `` forward '' or `` backward '' is assigned at random in the simulation . the comparison of our results with experimental data is shown in fig.20 . it is found that our model reproduces well experimental data for every @xmath73 . this correlation is usually parameterized by a linear form : @xmath237 the values of the parameters @xmath204 and @xmath205 extracted from the @xmath3-model and the corresponding experimental values are given in table v. + * figure 20 . * + * table v * + + the correlation strength @xmath205 depends on the size of @xmath1 . when @xmath1 becomes large , the correlation strength @xmath205 also becomes large . when the multiplicity distribution is extremely narrow , the correlation strength @xmath205 is negative . for example , if the multiplicity distribution is delta function type , @xmath238 , the correlation strength @xmath205 is @xmath239 . note that the dispersion of the multiplicity distribution is also sensitive to the size of @xmath1 . increase of @xmath1 enhances the dispersion of the multiplicity distribution . this enhancement of the dispersion also increases the correlation strength @xmath205 . we found that the forward - backward correlation is not significantly affected by the energy - momentum conservation . we have investigated various correlations and fluctuations observed in multiparticle production in @xmath0 annihilation by using a new statistical model constructed on the basis of the maximum entropy method . this model allows us to investigate the crucial roles of the bose - einstein correlations ( bec ) in multiparticle production phenomena . the model has three parameters @xmath43 , @xmath44 and @xmath1 . the `` partition '' temperature @xmath43 and the `` chemical '' potential @xmath44 characterize the single particle spectra . the bec is characterized by the third parameter @xmath1 . based on this model we have constructed two kinds of event generators which correspond to two extreme cases . one case is the @xmath3-model which assumes that all pions are produced directly , i.e. , @xmath240 . the other is the @xmath2-model where it is assumed that all pions are produced via the decay of @xmath2 mesons , i.e. , @xmath241 . in the course of the event generation , energy - momentum and charge conservations are imposed by event selection . thus we can study the effects on single particle spectra and correlations caused by these conservation laws . we found that some observables are significantly affected by them . + various kinds of the experimental data on single particle spectra and many particle correlations are well reproduced by our model . we have compared the results obtained from our simulations with experimental data on multiplicity distributions , rapidity distributions and rapidity dependence of the mean transverse momentum . for many particle correlations , we compare our calculations with experimental data on factorial moments , bose - einstein correlations , 2-particle rapidity correlations and forward - backward correlations . we have also calculated the charge correlations in the rapidity space . we hope experimentalists will measure this observable . + our results for all observables on correlations , including the dispersion of the multiplicity distributions , exhibit a strong @xmath1 dependence . we found that @xmath1 plays an essential role in explaining the behavior of some 2-particle correlation functions , scaled factorial moments and so on . once the value of the parameter @xmath1 is determined by fitting our result on the rapidity dependence of the dispersion of the multiplicity distribution to that of the experimental data , other correlation and fluctuation data are systematically reproduced by using the same @xmath1 value . the parameter @xmath1 may correspond to an effective correlation length ( in the rapidity space ) of the bec . constancy of the size of the @xmath1 in the whole rapidity space is the most characteristic point in our model . this simple assumption may be checked by measuring the correlation @xmath233 at various rapidity regions . there are possibilities that it depends on the rapidity @xmath146 and/or the multiplicity . + in bose - einstein correlations and 2-particle rapidity correlations , in particular , we observe a clear difference between the prediction from the @xmath3-model and that from the @xmath2-model . we found that the @xmath2-model gives better agreement with those experimental data than the @xmath3-model . this means that two - particle correlations are sensitive to production and decay processes of resonances and experimental data on those observables suggest that there are significant contribution from resonance decay . no significant difference between the @xmath3-model and the @xmath2-model is observed in the single particle spectra and other correlation data . finally , we would like to point out two important aspects of our model . first , we would like to emphasize that the bec are incorporated on event - by - event basis in our model . it thus provides a useful theoretical tool for event - by - event analysis of the bec . this is an important feature of our model not shared by any other event generators . second , information on the space - time structure of multiparticle production is apparently not contained in our statistical model . nevertheless , it gives the bec from which one can extract the information on the `` apparent '' source size and the chaoticity . it thus appears that the information on the space - time structure is `` hidden '' in our model . the fundamental parameter @xmath1 may have some relevance to the question . 99 see for example , + d. h. boal , rev.mod.phys,*62*(1990 ) , 553 ; m. gyulassy , s. k. kauffmann and l. w. wilson , phys.rev.*c20*(1979 ) , 2267 ; b. lrstad , int.j.mod.phys.*a4*(1989 ) , 2861 . a. bialas and p. peschanski , nucl.phys.*b273*(1986 ) , 703 . a. bialas and p. peschanski , nucl.phys.*b308*(1988 ) , 857 . m. g. bowler , z.phys . * c29 * ( 1986 ) , 617 . s. pratt , phys.rev.lett.*53*,(1984 ) , 1219 ; j. p. sullivan , phys.rev.lett.*70*,(1993 ) , 3000 . b. andersson and w. hofmann , phys.lett.*169b*(1986 ) , 364 ; m. g. bowler , phys.lett.*180b*(1986 ) , 299 ; x .artru and m. g. bowler , z.phys.*c37*(1988 ) , 293 . k. kadija , p. seyboth , phys.lett.*b287*(1992 ) , 363 ; s. haywood , ral-94 - 07 , july 1994 . e. t. jaynes , phys.rev.*106*(1957 ) , 620 . f. takagi and t. tsukamoto , phys.rev*d38*(1988 ) , 288 ; g. wilk and z. wodarczyk phys.rev.*d43*(1991 ) , 794 . see for example , l . van hove , rev.mod.phys.*36*(1964 ) , 655 ; nucl.phys.*b9*(1969 ) , 331 ; a. g. frodesen and p. nybrog , nucl.phys.*b81*(1974 ) , 283 . w. j. knox , phys.rev.*d10*,(1974 ) , 65 ; a. giovannini , nouvo cim.*a15*(1973 ) , 543 ; p. carruthers and c.c.shih , phys.lett.*b127*(1983 ) , 242 ; a. giovannini , l. van hove , z.phys.*c30*(1986 ) , 391 . t. t. chou , c. n. yang and e.yen , phys.rev.lett * 54*(1985 ) , 510 ; t. t. chou and c. n. yang , phys.rev.*d32*(1985 ) , 1692 . tasso collab . , w. braunschweig et al , z.phys.*c45*(1989 ) , 193 . delphi collab . , p. abreu et al , z.phys.*c52*(1991 ) , 271 . tasso collab . , m. althoff et al , z.phys.*c22*(1984 ) , 307 . tasso collab . , w. braunschweig et al , phys.lett.*b231*(1989 ) , 548 . tasso collab . , m. althoff et al , z.phys.*c29*(1985 ) , 347 . delphi collab . , p. abreu , et al , phys.lett . * 247*(1990 ) , 137 . delphi collab . , p. abreu et al , phys.lett.*b286 * ( 1992 ) , 201 . delphi collab . , p .abreu et al , z.phys.*c50*(1991 ) , 185 . aleph collab . , d.decamp , et al , z.phys.*c53 * ( 1992 ) , 21 . aleph collab . , d. decamp et al , z.phys.*c54*(1992 ) , 75 . b. andersson , g. gustafson , t.sjstrand , phys.lett.*b94*(1980 ) , 211 . hoyer et al , nucl.phys.*b161*(1979 ) , 34 ; a. ali et al , z.phys.*c2*(1979 ) , 33 . * fig.4 * ( a ) : kno scaling of the multiplicity distributions in the @xmath3- model at energies @xmath73=14.0 , 34.5 and 91.2 gev . ( b ) : comparison of the @xmath3- model(solid line ) with the experimental data for energy @xmath73=91.2 gev with @xmath251 6.5(full phase space ) , 2.0 and 1.0 . * fig.8 * ( a ) : rapidity dependence of the mean transverse momentum @xmath148 for @xmath101 14.0 , 34.5 and 91.2 gev . ( b ) : effect of the thrust axis and/or the energy - momentum conservation for energy @xmath101 34.5 gev . * fig.11 : * comparisons of the results for @xmath172 from the @xmath3- and @xmath2- model with the experimental data for ( a ) @xmath101 34.5 gev and ( b ) @xmath101 91.2 gev . the number of unlike pairs is used as the reference . * fig.16 * ( a ) : comparison of the result from the @xmath3-model with experimental data on the 2-particle rapidity correlation function @xmath230 at @xmath73= 34.5 gev for ( a ) the trigger i [ -5.50,-2.50],(b ) the trigger i@xmath4i [ -2.50,-1.50 ] , ( c ) the trigger i@xmath4i@xmath4i [ -1.50,-0.75 ] and ( d ) the trigger i@xmath4v [ -0.75,0.00 ] . * fig.17 : * the 2-particle rapidity correlation functions @xmath226 and @xmath227 in the @xmath3-model for @xmath73= 34.5 gev with ( a ) the trigger i [ -5.50,-2.50],(b ) the trigger i@xmath4i [ -2.50,-1.50 ] , ( c ) the trigger i@xmath4i@xmath4i [ -1.50,-0.75 ] and ( d ) the trigger i@xmath4v [ -0.75,0.00 ] . * fig.18 : * comparison of the results of @xmath2- model with experimental data on the 2-particle rapidity correlation function @xmath230 at @xmath73= 34.5 gev for ( a ) the trigger i [ -5.50,-2.50],(b ) the trigger i@xmath4i [ -2.50,-1.50 ] , ( c ) the trigger i@xmath4i@xmath4i [ -1.50,-0.75 ] and ( d ) the trigger i@xmath4v [ -0.75,0.00 ] .
a new statistical model for multiparticle production in @xmath0 annihilation is proposed based on the idea of the longitudinal phase space with limited transverse momentum . the longitudinal rapidity space is divided into cells of equal size in order to take into account the bose - einstein correlations(bec ) with a finite correlation length @xmath1 . the maximum entropy method is used to determine the probability distributions of the final state pions ( or @xmath2 mesons ) for a given mean multiplicity , mean transverse momentum and mean total energy . event simulation based on our model is performed in two extreme cases , a @xmath3-model and a @xmath2-model . the @xmath3-model assumes that only pions are produced directly . on the other hand , the @xmath2-model assumes that only @xmath2 mesons are produced directly and they decay into pions . a good overall fit to experimental data from petra to lep energy regions is obtained for @xmath1 ranging from 0.6 to 1.2 in the @xmath3-model . we found that the bec plays a very important role to reproduce various correlation data . in some correlation data , resonance effect and conservation laws are also important . = -45pt = 0 cm = 0 cm = 24.00 cm = 16 cm pacs : 12.40.ee , 13.65.+i , 02.70.lq , 05.40.+j , 25.75.gz .
the endemic carnivorous plant venus flytrap ( dionaea muscipula ellis ) produces a rosette of leaves , each divided into two parts : the lower part called the lamina and the upper part called the trap . the trap catches prey by very rapid movement of its bilobed halves that shut when the trigger hairs protruding from the upper leaf epidermis are stimulated by touch . at room temperature , two touches activate the trap , which snaps shut in a fraction of second ( juniper et al . , 1989 ) . at higher temperature ( 3540 c ) only one stimulus is required for trap closure ( brown and sharp , 1910 ) . the stimulation of trigger hairs activates mechanosensitive ion channels and generates a receptor potential , which induces an action potential . electrical signals are the immediate cause of the trap movements irrespective of the way in which the signal is triggered ; for example by mechanical stimulation or by electrostimulation ( volkov et al . , 2007 , 2008a , b , c , 2009a , b ) . in animals , the ionic mechanism of the action potential of axons depends on inward - flowing na ( depolarization ) and outward - flowing k ions ( repolarization ) , whereas the excitation of plant cells depends on ca , cl , and k ions ( fromm and lautner , 2007 ) . the action potentials in dionaea have been extensively studied ( e.g. burdon - sanderson , 1873 ; affolter and olivo , 1975 ; hodick and sievers , 1986 , 1988 , 1989 ; sibaoka , 1991 ; trebacz and sievers , 1998 ; krol et al . , 2006 ; volkov et al . , 2007 , 2008a , b , c , 2009a , b ) . they propagate from mechanosensitive trigger hairs of the lobe to the trap midrib , more rapidly across the lower ( abaxial ) surface than across the upper one , while they are not recorded in adjacent lamina ( burdon - sanderson , 1873 ; burdon - sanderson and page , 1876 ; williams and pickard , 1980 ; volkov et al . , 2007 ) . ( 2007 ) found that the generated action potential had a duration of 1.5 ms and a velocity of 10 m s. trigger hair - induced generation of action potentials is not associated only with trap closure . the struggling of the entrapped prey in the closed trap results in generation of further action potentials which cease to occur when the prey stops moving . over 100 action potentials were recorded in the trap with prey in the first 2 h and the mechanical stimulation triggered secretion of digestive fluid ( affolter and olivo , 1975 ; lichtner and williams , 1977 ) . in a previous study it was shown that repeated irritation of trigger hairs temporarily reduced the rate of photosynthesis ( an ) and the effective photochemical quantum yield of photosystem ii ( psii ) , and stimulated the rate of respiration ( rd ) in the traps but not in the adjacent laminae ( pavlovi et al . , 2010 ) . these findings are not surprising because the inhibitory effect of electrical signals on an and psii has also been well documented in non - carnivorous plants ( koziolek et al . , 2003 ; lautner et al . , 2005 ; bulychev and kamzolkina , 2006a , b ; hlavkov et al . , 2006 ; kaiser and grams , 2006 ; fromm and lautner , 2007 ; krupenina and bulychev , 2007 , 2008 ; grams et al . , 2009 ) . however , the exact mechanism underlying the photosynthetic limitation caused by electrical signals is not yet known . it is difficult to conclude whether the changes in psii , which measures the proportion of light absorbed by chlorophyll associated with psii that is used in photochemistry ( for definition , see genty et al . , 1989 ; maxwell and johnson , 2000 ) , are the reason for or just a consequence of decreased carboxylation efficiency . in fact , reduced carboxylation efficiency decreases psii , which prevents overexcitation of psii and protects it against photoinhibition ( for a review , see kramer et al . , 2004 ) . it has been proposed that subcellular alternations in ion fluxes ( e.g. ca ) and ph may be involved in the photosynthetic responses , which modify the enzymatic activities in the cytoplasm or chloroplast ( lautner et al . , 2005 ; bulychev and kamzolkina , 2006a , b ; krupenina and bulychev , 2007 ) . bulychev and kamzolkina ( 2006a , b ) found that the depression of electron transport after action potentials in cells of chara was largely due to non - photochemical quenching ( npq ) in psii . ( 2003 ) suggest that transient knockout of photosynthesis mediated by electrical signals in mimosa pudica is too fast to be a result of zeaxanthin - dependent npq or chemical signals , as was later proposed by hlavkov et al . ( 2006 ) , and propose that the rapid decline of psii might result from direct interference with electron transport chains in chloroplasts through direct impact of electrical signals . in addition , a direct effect of the electrical field on charge separation and recombination in the reaction centre of psii can not be excluded ( meiburg et al . , 1983 ; dau and sauer , 1991 , 1992 ; bulychev and vredenberg , 1999 ; vredenberg and bulychev , 2002 , 2003 ; vredenberg et al . , 2009 ) . with the present state of knowledge it is still difficult to conclude what is the site effect of electrical signal - induced inhibition of photosynthesis . here a detailed analysis of chlorophyll a fluorescence kinetics simultaneously with gas exchange measurements is provided during irritation of trigger hairs , which induce the generation of action potentials in d. muscipula . first , the relationship between electrical signals and chlorophyll fluorescence in the light at atmospheric co2 concentration was examined . in the second experiment , the calvin cycle reactions were inhibited by lowering the co2 concentration to zero , while electrons still move on alternative electron acceptors , allowing determination of whether electrical signals have a direct impact on the electron transport chain . in the dark , the maximum quantum yield of psii ( fv / fm ) together with fast chlorophyll fluorescence induction kinetics ( o - j - i - p ) , reflecting the filling up of the psii electron acceptor plastoquinone pools qa and qb , were measured in the presence of electrical signals . are the primary targets of electrical signal - induced inhibition dark or light reactions of photosynthesis ? twenty 3- or 4-year - old d. muscipula j. ellis plants were grown in a growth chamber at an irradiance of 150 mol m s photosynthetic active radiation ( par ) and a 14/10 h light / dark period , in well - drained peat moss in plastic pots irrigated with distilled water . the trap was closed by mechanical stimulation and the leaf was cut near the base . the trap and thin wire ( 0.1 mm diameter ) placed in the closed trap were sealed into a leaf cuvette ( plc6 , pp - systems , hitchin , uk ) , which monitors co2 and h2o exchange . the base of the lamina protruding outside the cuvette was submerged in distilled water in an eppendorf tube to prevent it drying out . the trigger hairs in the closed trap in a hermetically closed cuvette were repeatedly stimulated for 15 s by moving the thin wire protruding outside . movements of the wire in the empty closed cuvette had no effect on co2 and h2o exchange , confirming that the movements of the wire had no effect on the gas - tight seal . measurements of chlorophyll a fluorescence were performed with a fluorcam fc-1000 lc ( photon systems instruments , brno , czech republic ) attached to the plc6 cuvette connected with a ciras-2 infrared gas analyser ( pp - system , hitchin , uk ) . before each measurement one leaf was cut and placed inside a plc6 cuvette . because the diameter of the cuvette window was 18 mm after 2 min , the minimal fluorescence ( f0 ) at a light intensity < 0.1 mol m s par was measured . thereafter , the maximal fluorescence ( fm ) was measured using a saturation pulse ( light intensity 3000 mol m s par , duration 800 ms ) . then an actinic light was switched on ( 80 mol m s par ) and , after stabilization of the net photosynthetic rate ( an ) , three saturation pulses were given every 60 s ( 3000 mol m s par , 800 ms duration ) for determination of the maximal fluorescence in the light - adapted state ( f'm ) afterwards the trigger hairs of the trap were mechanically stimulated by manipulation of the wire protruding outside the cuvette for 15 s. after 17 s a fourth saturation pulse was given followed by the remaining five pulses at regular 60 s intervals . in some experiments , after 17 s the actinic light was switched off and f'0 was recorded for estimation of the excitation pressure ( 1qp ) . photosynthetic parameters ( fv / fm , psii , npq , and 1qp ) were calculated according to maxwell and johnson ( 2000 ) . for definition of the parameters , simultaneously , the infrared gas analyser monitored co2 and h2o exchange every 2 s at a leaf temperature of 221 c , ambient co2 concentration of 380 l l , a relative air humidity of 6070% , and a light intensity of 80 mol m s par ( red - emitting leds , =620 nm ) . in the second experiment the measurements were done in exactly the same way , but without co2 ( 1 l finally , the whole experiment was performed in the dark at ambient co2 concentration of 380 l l. changes in the co2 concentration in the measuring chamber were recorded with a constant delay of 9 s ( the time taken for gas to pass from the cuvette to the infrared gas analyser ) . this delay was taken into account in figures presented here , and the bold lines on the x - axis were moved 9 s to the left . after measurements , the leaves were dried at 70 c for 5 d , weighed , and the an and rd were calculated in nmol co2 g dw s. data shown are representative of a total of five independent measurements . at high excitation irradiance , dark - adapted leaves show characteristic polyphasic fluorescence kinetics with four distinct steps named o - j - i - p ( for reviews , see strasser et al . , 2004 ; lazr , 2006 ) . because vredenberg and bulychev ( 2002 ) hypothesized that the i - p phase may be under photoelectrochemical control , the polyphasic increase in chlorophyll a fluorescence in the d. muscipula trap was measured in control ( non - irritated ) and irritated traps using a fluorpen fp 100max ( photon systems instruments , brno , czech republic ) . the fast increase in chlorophyll a fluorescence was measured over a time span of 10 s to 1 s. before the measurements , the trap was closed and dark adapted for 30 min . then the fast chlorophyll a fluorescence induction kinetics were measured in non - irritated traps . after 30 min in the dark the same trap was stimulated by the thin wire protruding outside the trap for 15 s. after 17 s the saturation pulse was given ( 2000 mol m s par , duration 1 s ) . the measurements were repeated three times on the same trap in the following order : control irritated control irritated control irritated with a 30 min dark interval between measurements to ensure that the previous saturation pulse had no effect on the shape of the curves and the differences are caused by trigger hair irritation . two - tailed paired t - test was used to find significant differences between the o , j , i , and p phases of the increase in chlorophyll a fluorescence ( statgraphics , centurion xv ) . each cut leaf was fixed inside a small measuring chamber so that the lamina was dipped in a mild saline solution ( 0.1 mm cacl2 , 0.5 mm kcl ) , while the electrodes were placed on the abaxial surface of the closed trap . a glass micropipette containing an ag / agcl wire and filled with 3 m kcl was mounted with a half cell holder and connected to the headstage of the probe . an identical electrode was placed in the measuring chamber to serve as a reference electrode . the electrodes were connected to the amplifier and the signal was recorded continuously during trap stimulation at a 1 khz rate of sampling frequency with home - made lab - view software . the action potentials were measured in the light ( 80 mol m s par ) at ambient co2 concentration , in an atmosphere without co2 ( 1 l five traps from different plants were selected for each treatment ; 10 measurements were performed . the statistical differences between treatments ( amplitude and number of action potentials ) were evaluated by student t - test ( statgraphics , centurion xv ) . twenty 3- or 4-year - old d. muscipula j. ellis plants were grown in a growth chamber at an irradiance of 150 mol m s photosynthetic active radiation ( par ) and a 14/10 h light / dark period , in well - drained peat moss in plastic pots irrigated with distilled water . the trap was closed by mechanical stimulation and the leaf was cut near the base . the trap and thin wire ( 0.1 mm diameter ) placed in the closed trap were sealed into a leaf cuvette ( plc6 , pp - systems , hitchin , uk ) , which monitors co2 and h2o exchange . the base of the lamina protruding outside the cuvette was submerged in distilled water in an eppendorf tube to prevent it drying out . the trigger hairs in the closed trap in a hermetically closed cuvette were repeatedly stimulated for 15 s by moving the thin wire protruding outside . movements of the wire in the empty closed cuvette had no effect on co2 and h2o exchange , confirming that the movements of the wire had no effect on the gas - tight seal . measurements of chlorophyll a fluorescence were performed with a fluorcam fc-1000 lc ( photon systems instruments , brno , czech republic ) attached to the plc6 cuvette connected with a ciras-2 infrared gas analyser ( pp - system , hitchin , uk ) . before each measurement one leaf was cut and placed inside a plc6 cuvette . because the diameter of the cuvette window was 18 mm after 2 min , the minimal fluorescence ( f0 ) at a light intensity < 0.1 mol m s par was measured . thereafter , the maximal fluorescence ( fm ) was measured using a saturation pulse ( light intensity 3000 mol m s par , duration 800 ms ) . then an actinic light was switched on ( 80 mol m s par ) and , after stabilization of the net photosynthetic rate ( an ) , three saturation pulses were given every 60 s ( 3000 mol m s par , 800 ms duration ) for determination of the maximal fluorescence in the light - adapted state ( f'm ) afterwards the trigger hairs of the trap were mechanically stimulated by manipulation of the wire protruding outside the cuvette for 15 s. after 17 s a fourth saturation pulse was given followed by the remaining five pulses at regular 60 s intervals . in some experiments , after 17 s the actinic light was switched off and f'0 was recorded for estimation of the excitation pressure ( 1qp ) . photosynthetic parameters ( fv / fm , psii , npq , and 1qp ) were calculated according to maxwell and johnson ( 2000 ) . for definition of the parameters , simultaneously , the infrared gas analyser monitored co2 and h2o exchange every 2 s at a leaf temperature of 221 c , ambient co2 concentration of 380 l l , a relative air humidity of 6070% , and a light intensity of 80 mol m s par ( red - emitting leds , =620 nm ) . in the second experiment the measurements were done in exactly the same way , but without co2 ( 1 l finally , the whole experiment was performed in the dark at ambient co2 concentration of 380 l l. changes in the co2 concentration in the measuring chamber were recorded with a constant delay of 9 s ( the time taken for gas to pass from the cuvette to the infrared gas analyser ) . this delay was taken into account in figures presented here , and the bold lines on the x - axis were moved 9 s to the left . after measurements , the leaves were dried at 70 c for 5 d , weighed , and the an and rd were calculated in nmol co2 g dw s. data shown are representative of a total of five independent measurements . at high excitation irradiance , dark - adapted leaves show characteristic polyphasic fluorescence kinetics with four distinct steps named o - j - i - p ( for reviews , see strasser et al . , 2004 ; lazr , 2006 ) . because vredenberg and bulychev ( 2002 ) hypothesized that the i - p phase may be under photoelectrochemical control , the polyphasic increase in chlorophyll a fluorescence in the d. muscipula trap was measured in control ( non - irritated ) and irritated traps using a fluorpen fp 100max ( photon systems instruments , brno , czech republic ) . the fast increase in chlorophyll a fluorescence was measured over a time span of 10 s to 1 s. before the measurements , the trap was closed and dark adapted for 30 min . then the fast chlorophyll a fluorescence induction kinetics were measured in non - irritated traps . after 30 min in the dark the same trap was stimulated by the thin wire protruding outside the trap for 15 s. after 17 s the saturation pulse was given ( 2000 mol m s par , duration 1 s ) . the measurements were repeated three times on the same trap in the following order : control irritated control irritated control irritated with a 30 min dark interval between measurements to ensure that the previous saturation pulse had no effect on the shape of the curves and the differences are caused by trigger hair irritation . two - tailed paired t - test was used to find significant differences between the o , j , i , and p phases of the increase in chlorophyll a fluorescence ( statgraphics , centurion xv ) . each cut leaf was fixed inside a small measuring chamber so that the lamina was dipped in a mild saline solution ( 0.1 mm cacl2 , 0.5 mm kcl ) , while the electrodes were placed on the abaxial surface of the closed trap . a glass micropipette containing an ag / agcl wire and filled with 3 m kcl was mounted with a half cell holder and connected to the headstage of the probe . an identical electrode was placed in the measuring chamber to serve as a reference electrode . the electrodes were connected to the amplifier and the signal was recorded continuously during trap stimulation at a 1 khz rate of sampling frequency with home - made lab - view software . the action potentials were measured in the light ( 80 mol m s par ) at ambient co2 concentration , in an atmosphere without co2 ( 1 l five traps from different plants were selected for each treatment ; 10 measurements were performed . the statistical differences between treatments ( amplitude and number of action potentials ) were evaluated by student t - test ( statgraphics , centurion xv ) . repeated 15 s irritation of trigger hairs in a closed trap decreased the effective photochemical quantum yield of psii ( psii ) , indicating that linear electron transport was inhibited . after stopping the mechanical irritation , the inhibition of psii was confined mainly to the digestive zone of the trap ( fig . this rapid inhibition resulted in a transient increase in the intercellular co2 concentration ( ci ; fig . 2b ) , while the stomatal conductance ( gs ) was not affected ( data not shown ; see pavlovi et al . , 2010 ) . during 15 s of irritation of trigger hairs in a closed trap , 3.70.7 ( 1 se ) ( maximum 7 ) action potentials with an average amplitude of 40.13.5 mv ( maximum 80 mv ) were recorded ( fig . 2a , inset ) . the detailed analysis of chlorophyll a fluorescence kinetics in the digestive zone of the trap revealed that the decrease of psii is caused at first by the increase in the steady - state fluorescence in the light ( ft ) , whereas maximal fluorescence in the light - adapted state ( f'm ) was not affected immediately after irritation ( fig . the fluorescence increase upon reduction of plastoquinone is due to a decrease in the rate of radical pair formation ( forward electron transfer ) and an increase in the rate of radical pair recombination ( backward electron transfer ) . the reduced plastoquinone pool results in increased excitation pressure at the psii reaction centre , promoting photoinhibition ( increased 1qp ; fig . 2d ) which is prevented by a series of down - regulatory processes known as npq . within 1 min after irritation , ft is quenched by npq as indicated by the large drop in f'm ( fig . f'm was rapidly reversed in darkness , indicating that it represents the fast relaxing energy state quenching ( qe ) rather than photoinhibitory quenching ( qi ; data not shown ) . spatiotemporal changes of effective photochemical quantum yield of psii ( psii ) in a d. muscipula closed trap assessed by chlorophyll fluorescence imaging . the trap was irritated by a thin wire between 162 s and 177 s. typical responses to trigger irritation in the venus flytrap ( d. muscipula ) at a light intensity of 80 mol m s par and an atmospheric co2 concentration of 380 l l at a leaf chamber temperature at 22 c . net photosynthetic rate ( an ; a ) , electrical signals ( a ; inset ) , intercellular co2 concentration ( ci ; b ) , chlorophyll fluorescence kinetics ( c ) , and chlorophyll fluorescence parameters , means 1 se ( d ) . psii , the effective photochemical quantum yield of psii , open circles ; 1qp , the excitation pressure , open triangles ; npq , the non - photochemical quenching , open squares . the duration of trigger hair irritation is denoted as a bold line on the x - axis . data shown are representative of a total of five measurements . because light and dark reactions of photosynthesis are coupled together by the production and consumption of atp and nadph , from the above - mentioned results it is difficult to conclude whether the decreased psii is a reason for or just a consequence of reduced an . transiently increased 1qp before induction of npq indicates that a traffic jam of electrons in the electron transport chain occurred . this is probably due to a decreased concentration of the oxidized form of nadp ( an electron acceptor from psi ) determined by a decreased activity of the calvin cycle . therefore , the concentration of co2 was decreased , to inhibit the dark reactions of photosynthesis , allowing the electrons to move on alternative electron acceptors ( e.g. o2 , activation of cyclic electron flow and photorespiration , n metabolism ) to observe the direct impact of action potentials on psii . the experiment in a co2-free atmosphere ( 1 l l ) showed the reverse effect of trigger hair irritation on psii , despite the same efflux of co2 ( fig . trigger hair irritation decreased ft and increased f'm , and thus psii slightly increased ( fig . the absence of co2 had not significant effect on action potentials , as the amplitude and number of pulses were comparable with those in the previous experiment ( number 3.20.5 , p=0.545 ; amplitude 37.23.2 mv , p=0.485 , fig . typical responses to trigger hair irritation in the venus flytrap ( dionaea muscipula ) at a light intensity of 80 mol m s par and an atmospheric co2 concentration of 1l l at a leaf chamber temperature of 22 c . net photosynthetic rate ( an ; a ) , electrical signals ( a ; inset ) , intercellular co2 concentration ( ci ; b ) , chlorophyll fluorescence kinetics ( c ) , and chlorophyll fluorescence parameters , means 1 se ( d ) . psii , the effective photochemical quantum yield of psii , open circles ; 1qp , the excitation pressure , open triangles ; npq , the non - photochemical quenching , open squares . the duration of trigger hair irritation is denoted as a bold line on the x - axis . data shown are representative of a total of five measurements . in the dark - adapted leaf the plastoquinone pool is oxidized that is , the reaction centres are open and calvin cycle enzymes are inactivated , allowing estimatation of the maximal photochemical activity of psii ( fv / fm ) . trigger hair irritation resulted in transient efflux of co2 from the trap , indicating that the increased respiration rate ( rd ) is the major contributor to the decreased an [ an is a function of rd and gross photosynthesis ( ag ) ( fig . trigger hair irritation had the opposite effect on fluorescence in dark - adapted and light - adapted traps at ambient co2 concentration . this indicates that the fv / fm , which is proportional to the quantum yield of o2 evolution from psii , was slightly higher after irritation ( fig . however , the effect of action potentials on the fluorescence in dark - adapted traps was much less obvious ( changes in f0 up to 4% ) than in light - adapted traps ( changes in ft up to 60% , and of in f'm up to 35% ; compare figs 2c and 4c ) ; therefore , the changes in fm were omitted in the calculation of npq . the amplitude and number of action potentials were comparable with our previous experiments , indicating that darkness had no effect on electrical signalling ( number 3.80.3 , p=0.837 ; amplitude 45.95.1 mv , p=0.332 ; fig . data from chlorophyll a fluorescence transient ( o - j - i - p ) values are the means 1 se from 18 measurements . statistical differences were evaluated by two - tailed paired student t - test ; significant differences before and after irritation of the same trap ( paired data ) are in bold . typical responses to trigger hair irritation in the venus flytrap ( dionaea muscipula ) in darkness and an atmospheric co2 concentration of 380 l l at a leaf chamber temperature of 22 c . net photosynthetic rate ( an ; a ) , electrical signals ( a ; inset ) , intercellular co2 concentration ( ci ; b ) , chlorophyll fluorescence kinetics ( c ) , and chlorophyll fluorescence parameter , means 1 se ( d ) . fv / fm , the maximal quantum yield of psii photochemistry , is shown by open circles . the duration of trigger hair irritation is denoted as a bold line on the x - axis . measurements of the polyphasic increase in chlorophyll a fluorescence ( o - j - i - p ) in dark - adapted leaves have advantages over a single parameter such as the well known fv / fm . the decrease in the fluorescence rise in the 20200 ms time range ( o - j - i rise ) was compensated by an increase in the rise in the 20200 ms time range ( i - p rise ; fig . the values of four distinct phases of the increase in chlorophyll a fluorescence ( o - j - i - p ) are summarized in table 1 . significant differences were found in o , j , and p phases of the increase in chlorophyll a fluorescence . chlorophyll a fluorescence transients in non - irritated ( black line ) and irritated ( grey line ) d. muscipula traps given on a logarithmic time scale . the results reported here and in a previous study ( pavlovi et al . , 2010 ) confirmed that the irritation of the trigger hairs and the subsequent generation of action potentials in the digestive zone of the closed trap of d. muscipula resulted in a transient decrease in psii and an ( figs 1 , 2 ) . the generation of action potentials and their negative effect on photosynthesis were confined to the trap and were not recorded in the adjacent lamina ( volkov et al . convincing evidence on the role of the electrical signals in the regulation of photosynthesis has been described by numerous authors ( herde et al . , 1999 ; , 2003 ; lautner et al . , 2005 ; bulychev and kamzolkina , 2006a , b ; hlavkov et al . , 2006 ; kaiser and grams , 2006 ; fromm and lautner , 2007 ; krupenina and bulychev , 2007 , 2008 ; grams et al . , 2009 ) . in accordance with krupenina and bulychev ( 2007 ) , the inhibition of psii and the rapid efflux of co2 are longer than the duration of the action potential itself . these authors called it the long - lived state effect of action potentials on photosynthesis . ( 2009 ) that if the electrical signals have an impact on cytosolic ph , changes in enzyme activity might play a role in photosynthetic limitation ( e.g. carbonic anhydrase , a ph - dependent enzyme important in the regulation of mesophyll conductance ) . bulychev and kamzolkina ( 2006a , b ) proposed that action potentials suppress the calvin cycle reactions by increasing [ ca ] in chloroplast stroma . ( 2009 ) found in isolated chloroplasts that the increase of [ ca ] had no effect on the psii . ( 2005 ) suggested direct involvement of increased [ ca ] in o2 formation of psii , and koziolek et al . ( 2003 ) proposed that the rapid decline in psii might result from an interference of the electron transport chains in chloroplasts through the direct impact of electrical signals . ( 2006 ) suggested that an increased level of jasmonic acid and abscisic acid had a direct inhibitory effect on the photosynthetic apparatus and stomata closure , respectively , in response to electrical signals evoked by local burning in tobacco . however , chemical signals are too slow to account for the photosynthetic response in sensitive plants ( e.g. mimosa or dionaea ) , as was concluded by koziolek et al . however no changes in gs were found during irritation of the trap in this and a previous study , and the stomatal limitation of photosynthesis in carnivorous d. muscipula can be excluded ( pavlovi et al . , 2010 ) . in this study evidence is provided that the decrease in psii is a consequence of reduced activity of enzymes involved in the dark reaction of photosynthesis , due to a feedback mechanism of co2 assimilation on electron transport rather than a direct effect of electrical signals on the light reaction , which seems not to be affected substantially . this assumption is supported by the observation that during the first seconds after trigger hair irritation in the light , the electron transfer chain became over - reduced ( increased 1qp ) before the lumen could be sufficiently acidified to initiate npq ( fig . 2d ) . rapid relaxation of npq in the dark indicates that energy state quenching ( qe ) is the major contributor to npq ( data not shown ) . the release of npq by nigericine and the rapid reversal of action potential - triggered npq in darkness in chara cells also indicates npq 's relationship to qe ( bulychev and kamzolkina , 2006a , b ; krupenina and bulychev , 2007 ) . a correlation between npq and zeaxanthin accumulation after 5 h in response to current application in solanum lycopersicum zeaxanthin dissipates excess excitation energy as heat and prevents photoinhibition of psii ( pospil , 1997 ) . absorption of sunlight that exceeds a plant 's capacity for co2 fixation results in a build up of the thylakoid ph that is generated by photosynthetic electron transport . the lumen acidification and subsequent activation of violaxanthin de - epoxidase , which catalyses the conversion of violaxanthin first to antheraxanthin and then to zeaxanthin and is connected to qe , might be explained by the decreasing atp consumption in the calvin benson cycle . cyclic electron flow around psi may also contribute to lumen acidification , because a role in down - regulation of psii via production of ph and subsequent activation of qe has been proposed ( mller et al . , 2001 ; kramer et al . , 2004 ; niyogi et al . , 2005 ) . however , a zeaxanthin - independent npq mechanism localized in the psii core complex or the role of lutein can not be excluded ; both are also activated by generation of ph and are rapidly relaxed in darkness . these types of quenching form rapidly and may precede zeaxanthin - dependent quenching ( ruban and horton , 1999 ; finazzi et al . it seems that electron transport is not directly inhibited by electrical signals . in the absence of co2 , when calvin cycle reactions are inhibited by unavailability of co2 substrate , 3d ) . even a slight decrease in ft and increase in f'm in the light resulted in higher psii ( fig . it is tempting to assume that a transient increase of ci after irritation , as a result of transiently increased rd , decreased 1qp and npq and slightly and transiently increased psii by the stimulation of the calvin cycle which consumes nadph and restores the oxidized form of nadp , an electron acceptor from psi ( fig . however , the possibility of a direct impact of the electrical signals on the charge separation recombination reaction in psii and subsequent increased fluorescence yield also can not be excluded , as discussed below . the changes in chlorophyll a fluorescence in dark - adapted traps and fv / fm are not so obvious as the changes in the light - adapted state ( with or without co2 ) and are rather minor ( fig . the polyphasic increase in chlorophyll a fluorescence has advantage over a single parameter such as the well known fv / fm and takes into account all the steps of sequential fluorescence increase upon sudden illumination . quantitative models enable calculation of the energy cascade from psii light absorption to electron transport using o - j - i - p curves ( for a review , see strasser et al . , 2004 ) . it has been proposed that the o step is the fluorescence signal coming from excited chlorophylls of light - harvesting antenna before the excitations reach the reaction centre of psii , the j step reflects light - driven accumulation of qa , and steps i and p reflect light - driven accumulation of qb and qb , respectively ; however , several other explanations have been proposed ( for reviews , see lazr , 2006 , 2009 ) . at first glance , it seems that trigger hair irritation and subsequent generation of action potentials in d. muscipula resulted in an increase in fv / fm and thus increased photochemical efficiency of psii ( table 1 ) . however , care must be taken in the interpretation of the results , because the models relating variable psii fluorescence and energy trapping are based on the assumption that the energetic state of psii reaction centres is determined and quantified by the redox state of qa ( two - state trapping model ) . a three - state trapping model , proposed by vredenberg ( 2000 , 2004 ) , suggests that the saturation of photochemistry does not necessarily result in saturation of the changes in fluorescence yield , as pheophytin ( pheo ) and oxidized secondary donor tyrosine ( yz ) may also act as efficient fluorescence quenchers of psii . therefore , any calculations of energy fluxes in psii according to the two - state trapping model ( strasser et al . , 2004 ) were avoided and only the differences at four distinct steps of the increase in chlorophyll a fluorescence were quantified ( table 1 ) . the decrease in the o - j - i rise and increase in the i - p rise in an irritated trap is in accordance with electrochemical stimulation of the fluorescence yield supplementary to photochemical quenching ( fig . 5 , pospil and dau , 2002 ; vredenberg and bulychev , 2002 , 2003 ; vredenberg , 2004 ; vredenberg et al . , 2009 ) . it was proposed that an electric field in the vicinity of the reaction centre could influence the chlorophyll fluorescence ( meiburg et al . , 1983 ; dau and sauer , 1991 , 1992 ; bulychev and vredenberg , 1999 ; vredenberg and bulychev , 2002 ; vredenberg , 2004 ; vredenberg et al . , apart from the influence of qa oxidation , the electrical field may exerts its effect on recombination of charges in psii by decreasing the gibbs free energy difference ( g0 ) between the excited states in the reaction centre of psii and the charge - separated state ( p680 pheo ) . as far as is known , this is the first time that the generation of action potentials has impact on yield of chlorophyll a fluorescence during the o - j - i - p transient , and provides convincing evidence that the fluorescent rise is under electrochemical control . ( 2006 ) found no changes in the fluorescence induction in response to variation potentials generated by tobacco leaf in response to local burning . it seems that the donor side inhibition of photosynthesis ( electrons from water ) was not significantly affected as the k step in the increase in chlorophyll a fluorescence has not appeared . ( 1997 ) concluded that a typical k step in the increase in chlorophyll fluorescence is due to the decrease in the continuous supply of electrons to the reaction centre of psii from water . because the effect of electrical signals on the fluorescence yield of psii in a dark - adapted trap of d. muscipula is relatively small , it is suggested that the main site effect of electrical signals on inhibition of photosynthesis is in dark reactions . for better understanding , 6 summarizes the hypothesis about the target of electrical signals on photosynthesis in d. muscipula . hypothesis about the effect of action potentials on photosynthesis in dionaea muscipula upon trigger hair irritation . in accordance with the present results , it is supposed that the main targets of action potential - induced inhibition of photosynthesis are dark reactions of photosynthesis ( 1 ) . suppression of calvin cycle reactions or co2 availability by inhibition of carbonic anhydrase ( an important part of the regulation of mesophyll conductance ) may decrease atp and nadph consumption . unavailability of adp and the oxidized form of nadp inhibits atp synthesis and linear electron transport ( 2 ) . this results in increased excitation pressure at psii ( 3 ) due to the accumulation of the reduced plastoquinone pool and increased emission of fluorescence ( 4 ) . inhibition of atp synthesis and probably also enhanced cyclic electron flow around psi ( 5 ) decrease the ph in the thylakoid lumen ( 6 ) . the decrease in ph within excess excitation energy is dissipated as heat , and chlorophyll fluorescence is quenched ( 7 ) . the result also support the hypothesis about the direct effect of electrical signals on charge separation recombination reactions in psii ( 8) , although the effect seems to be small rather than substantial . the results of the experiment performed in the dark indicate that rapid efflux of co2 originates not only from inhibition of photosynthesis but also from stimulation of respiration ( fig . a transient rise in rd after generation of action potentials was also documented in the liverwort conocephalum conicum ( dziubinska et al . , 1989 ) . the results suggest that at least some of the energy connected with the rise of rd is utilized for the restoration of the state of the ionic balance ( i.e. restores the resting state ) . jaffe ( 1973 ) and williams and bennet ( 1982 ) found that during trap closure in d. muscipula , 29% of atp is lost . subsequent availability of an increased concentration of adp may stimulate enzymes in early steps of the respiration pathway ( for an overview , see taiz and zeiger , 2002 ) . however , the role of atp is not only in rapid closure of the trap , but also in generation of action potentials , as suggested by dziubinska et al . ( 1989 ) , because repeated mechanical irritation in a closed trap resulted in transient stimulation of rd ( fig . the action potentials generated by trigger hair irritation in the carnivorous plant d. muscipula have an impact on both light and dark reactions of photosynthesis as chlorophyll a fluorescence measurements indicate . however , the changes in the yield of chlorophyll a fluorescence in dark - adapted traps are small in comparison with the changes in the light - adapted state . it is concluded that the main target of action potential - induced inhibition of photosynthesis is in the dark reaction , whereas the decreased electron transport ( expressed as psii ) is only a consequence of impaired co2 assimilation , preventing photooxidative damage of psii by dissipation of excitation energy via npq . recombination reactions in psii ; in this case the effect is small rather than substantial but provides important and convincing evidence about the electrochemical component of chlorophyll a fluorescence in vivo .
mechanical stimulation of trigger hairs on the adaxial surface of the trap of dionaea muscipula leads to the generation of action potentials and to rapid leaf movement . after rapid closure secures the prey , the struggle against the trigger hairs results in generation of further action potentials which inhibit photosynthesis . a detailed analysis of chlorophyll a fluorescence kinetics and gas exchange measurements in response to generation of action potentials in irritated d. muscipula traps was used to determine the site effect of the electrical signal - induced inhibition of photosynthesis . irritation of trigger hairs and subsequent generation of action potentials resulted in a decrease in the effective photochemical quantum yield of photosystem ii ( psii ) and the rate of net photosynthesis ( an ) . during the first seconds of irritation , increased excitation pressure in photosystem ii ( psii ) was the major contributor to the decreased psii . within 1 min , non - photochemical quenching ( npq ) released the excitation pressure at psii . measurements of the fast chlorophyll a fluorescence transient ( o - j - i - p ) revealed a direct impact of action potentials on the charge separation recombination reactions in psii , although the effect seems to be small rather than substantial . all the data presented here indicate that the main primary target of the electrical signal - induced inhibition of photosynthesis is the dark reaction , whereas the inhibition of electron transport is only a consequence of reduced carboxylation efficiency . in addition , the study also provides valuable data confirming the hypothesis that chlorophyll a fluorescence is under electrochemical control .
Dan Conner will rise from the dead in the new version of “Roseanne.” Fans of the classic original version of ABC’s blue-collar sitcom will recall that the character of Roseanne’s husband Dan, played by John Goodman, was said to have died of a heart attack on the series finale. It was part of a darker, unexpected course that the series took in its final season in which star Roseanne Barr had complete creative control. But ABC entertainment President Channing Dungey told reporters at the Television Critics Assn. press tour on Sunday in Beverly Hills that the patriarch's heart will beat anew as part of the midseason eight-episode revival to air during the 2017-18 TV season. “I wouldn’t say that it is ignoring the events of the finale, but I can confirm that Dan is definitely still alive,” she said. Dungey also said the updated series will be true to what it was when fans embraced it during the years when it was among the top-rated shows on network television that addressed the challenges faced by working-class families. The series ran on ABC from 1988 to 1997 and has remained popular in syndication. The original cast has signed on to participate with the exception of Johnny Galecki, who stars on the CBS series "The Big Bang Theory." Dungey said ABC is in talks with the actor, who played David Healy on the series. “We feel very confident that it returns to the show that we really know and love,” Dungey said. “It’s very much tonally similar to the original show. It’s unflinching, it is honest, it is irreverent at times and very, very funny.” The wild card aspect of the deal ABC made to get the series was to allow Barr to make the show with little input from the network's programming executives. ABC had to agree to that provision to match an offer made by the streaming service Netflix. ABC will also find itself back in the business of dealing with the unpredictable real-life Roseanne, who uses her Twitter feed as a platform for her unconventional political views. (Barr sought the Green Party nomination for president in 2012). Dungey noted that Barr announced a few weeks ago that her son is going to be taking over her Twitter feed in the near future. “We did not ask her to do that, but she did make that decision,” Dungey said. “What we’ve heard from Roseanne is she is very excited about the show and wants to be very focused on the show.” Dungey noted that she was not concerned about what one reporter described as “wacky conspiracy stuff” that appeared on Barr’s Twitter feed in recent days. “I try to just worry about the things that I can control,” Dungey said. In recent months, ABC already had its share of controversy from “Bachelor in Paradise,” its summer reality spinoff of “The Bachelor.” Production was suspended on June 11 after it was revealed that two intoxicated contestants were filmed having a sexual encounter on the set. Questions were raised on whether the female contestant involved had consented. Once production resumed June 20, after the show’s studio Warner Bros. conducted an internal investigation that found no wrongdoing, ABC aired a promotional spot that appeared to capitalize on the scandal. Dungey said the spot was pulled after a rash of bad press that suggested the network was insensitive to a situation in which the safety of the contestants was in question. “The promo in question did not refer to the alleged incident at all,” Dungey said. “It actually was comprised of a bunch of tweets from 'Bachelor' [fans] who were expressing their potential disappointment that there wouldn’t be a season and then the joy that there would be. We thought that it was cheeky and funny and sort of in line with the show. However, the response told us otherwise, and then we pulled it." Dungey would not go into detail on what precautions were taken on the "Bachelor in Paradise" set following the investigation, noting it was handled by Warner Bros. "It certainly has brought to light some safety issues that we want to make sure that we are more on top of moving forward in terms of making sure that our contestants are safe and protected at all times," she said. ||||| Tweet with a location You can add location information to your Tweets, such as your city or precise location, from the web and via third-party applications. You always have the option to delete your Tweet location history. Learn more ||||| Welcome back to life, Dan Conner! Though he met his maker in the 1997 series finale, John Goodman’s character will be present when the show returns on ABC this season. Production is expected to begin in October for the show’s mid-season berth. “I don’t want to talk too specifically, but I wouldn’t say we’ll ignore the events of the finale,” ABC Entertainment President Channing Dungey told reporters Sunday in Beverly Hills, Calif. “Dan is definitely still alive.” In fact, Goodman did appear on stage at ABC’s May upfront with Roseanne Barr and costars Laurie Metcalf, Michael Fishman, and Lecy Goranson. Roseanne originally ended its ABC run with Dan having a fatal heart attack. Everett Collection; Albert L. Ortega/Getty Images It’s certainly not unprecedented for Roseanne to ignore how it wrapped the action in the series ender. The writers of Will & Grace told EW that it will ignore how the NBC series ended by giving the lead characters spouses and kids. The show will return with Will (Eric McCormack) and Grace (Debra Messing) still living together in their New York City apartment. In other casting news, Dungey said they remain in talks with The Big Bang Theory’s Johnny Galecki about reprising his role as David Healy. As for the brand of comedy, Dungey promised the show will “very much tonally be similar to the original” in that it will be “unflinching, honest and irreverent at times. Very topical.” Though the show won’t specifically address the current administration, there are topical issues that Roseanne will tackle, she added, like “how difficult it is to get medical insurance.”
– The Roseanne revival is set to air on ABC this fall, and one character in particular will make a surprising comeback. Dan Conner, the family patriarch played by John Goodman, was revealed in the series finale to have died of a heart attack—but in the ABC reboot, "Dan is definitely still alive," ABC Entertainment President Channing Dungey informed reporters Sunday, per EW.com. How the show plans on pulling this off isn't being unmasked yet, but Dungey added that "I wouldn't say we'll ignore the events of the finale." The Los Angeles Times reports that ABC won a bidding war for the show with Netflix by agreeing to give star Roseanne Barr almost complete creative control, which puts the network "back in the business of dealing with the unpredictable real-life Roseanne." Among concerns noted by some are the comedian's Twitter feed, which often promotes her strongly held political positions (described by one reporter as "wacky conspiracy stuff"). Dungey shrugged that particular issue off, noting Roseanne's son will be taking over her Twitter feed and that "I try to just worry about the things that I can control."
SECTION 1. SHORT TITLE. This Act may be cited as the ``Reciprocity Ensures Streamlined Use of Lifesaving Treatments Act of 2015''. SEC. 2. RECIPROCAL MARKETING APPROVAL FOR CERTAIN DRUGS, BIOLOGICAL PRODUCTS, AND DEVICES. The Federal Food, Drug, and Cosmetic Act is amended by inserting after section 524A of such Act (21 U.S.C. 360n-1) the following: ``SEC. 524B. RECIPROCAL MARKETING APPROVAL. ``(a) In General.--A covered product with reciprocal marketing approval in effect under this section is deemed to be subject to an application or premarket notification for which an approval or clearance is in effect under section 505(c), 510(k), or 515 of this Act or section 351(a) of the Public Health Service Act, as applicable. ``(b) Eligibility.--The Secretary shall, with respect to a covered product, grant reciprocal marketing approval if-- ``(1) the sponsor of the covered product submits a request for reciprocal marketing approval; and ``(2) the request demonstrates to the Secretary's satisfaction that-- ``(A) the covered product is authorized to be lawfully marketed in one or more of the countries included in the list under section 802(b)(1); ``(B) absent reciprocal marketing approval, the covered product is not approved or cleared for marketing, as described in subsection (a); ``(C) the Secretary has not, because of any concern relating to the safety or effectiveness of the covered product, rescinded or withdrawn any such approval or clearance; ``(D) the authorization to market the covered product in one or more of the countries included in the list under section 802(b)(1) has not, because of any concern relating to the safety or effectiveness of the covered product, been rescinded or withdrawn; ``(E) the covered product is not a banned device under section 516; and ``(F) there is a public health or unmet medical need for the covered product in the United States. ``(c) Safety and Effectiveness.-- ``(1) In general.--The Secretary-- ``(A) may decline to grant reciprocal marketing approval under this section with respect to a covered product if the Secretary affirmatively determines that the covered product-- ``(i) is a drug that is not safe and effective; or ``(ii) is a device for which there is no reasonable assurance of safety and effectiveness; and ``(B) may condition reciprocal marketing approval under this section on the conduct of specified postmarket studies, which may include such studies pursuant to a risk evaluation and mitigation strategy under section 505-1. ``(2) Report to congress.--Upon declining to grant reciprocal marketing approval under this section with respect to a covered product, the Secretary shall-- ``(A) include the denial in a list of such denials for each month; and ``(B) not later than the end of the respective month, submit the list to the Committee on Energy and Commerce of the House of Representatives and the Committee on Health, Education, Labor and Pensions of the Senate. ``(d) Request.--A request for reciprocal marketing approval shall-- ``(1) be in such form, be submitted in such manner, and contain such information as the Secretary deems necessary to determine whether the criteria listed in subsection (b)(2) are met; and ``(2) include, with respect to each country included in the list under section 802(b)(1) where the covered product is authorized to be lawfully marketed, as described in subsection (b)(2)(A), an English translation of the dossier issued by such country to authorize such marketing. ``(e) Timing.--The Secretary shall issue an order granting, or declining to grant, reciprocal marketing approval with respect to a covered product not later than 30 days after the Secretary's receipt of a request under subsection (b)(1) for the product. An order issued under this subsection shall take effect subject to Congressional disapproval under subsection (g). ``(f) Labeling; Device Classification.--During the 30-day period described in subsection (e)-- ``(1) the Secretary and the sponsor of the covered product shall expeditiously negotiate and finalize the form and content of the labeling for a covered product for which reciprocal marketing approval is to be granted; and ``(2) in the case of a device for which reciprocal marketing approval is to be granted, the Secretary shall-- ``(A) classify the device pursuant to section 513; and ``(B) determine whether, absent reciprocal marketing approval, the device would need to be cleared pursuant to section 510(k) or approved pursuant to section 515 to be lawfully marketed under this Act. ``(g) Congressional Disapproval of FDA Orders.-- ``(1) In general.--A decision of the Secretary to decline to grant reciprocal marketing approval under this section shall not take effect if a joint resolution of disapproval of the decision is enacted. ``(2) Procedure.-- ``(A) In general.--Subject to subparagraph (B), the procedures described in subsections (b) through (g) of section 802 of title 5, United States Code, shall apply to the consideration of a joint resolution under this subsection. ``(B) Terms.--For purposes of this subsection-- ``(i) the reference to `section 801(a)(1)' in section 802(b)(2)(A) of title 5, United States Code, shall be considered to refer to subsection (c)(2); and ``(ii) the reference to `section 801(a)(1)(A)' in section 802(e)(2) of title 5, United States Code, shall be considered to refer to subsection (c)(2). ``(3) Effect of congressional disapproval.--Reciprocal marketing approval under this section with respect to the applicable covered product shall take effect upon enactment of a joint resolution of disapproval under this subsection. ``(h) Applicability of Relevant Provisions.--The provisions of this Act shall apply with respect to a covered product for which reciprocal marketing approval is in effect to the same extent and in the same manner as such provisions apply with respect to a product for which approval or clearance of an application or premarket notification under section 505(c), 510(k), or 515 of this Act or section 351(a) of the Public Health Service Act, as applicable, is in effect. ``(i) Fees for Request.--For purposes of imposing fees under chapter VII, a request for reciprocal marketing approval under this section shall be treated as an application or premarket notification for approval or clearance under section 505(c), 510(k), or 515 of this Act or section 351(a) of the Public Health Service Act, as applicable. ``(j) Outreach.--The Secretary shall conduct an outreach campaign to encourage the sponsors of covered products that are potentially eligible for reciprocal marketing approval to request such approval. ``(k) Covered Product Defined.--In this section, the term `covered product' means a drug, biological product, or device.''.
Reciprocity Ensures Streamlined Use of Lifesaving Treatments Act of 2015 This bill amends the Federal Food, Drug, and Cosmetic Act to establish a reciprocal marketing approval process that allows for the sale of a drug, biological product, or medical device that has not been approved by the Food and Drug Administration (FDA) if the product is approved for sale in another country. For a product to be granted reciprocal marketing approval, the product's sponsor must submit a request to the FDA that demonstrates: (1) the product may be sold in at least one country from a specified list of countries, (2) the FDA and listed countries have not withdrawn approval of the product because of safety or effectiveness concerns, and (3) there is a public health or unmet medical need for the product. The FDA may: (1) require postmarket studies of a product granted reciprocal marketing approval, or (2) decline to approve a product that is not safe and effective. The FDA must grant or decline reciprocal marketing approval not later than 30 days after receiving a request. During that period, the FDA and product sponsor must negotiate and finalize product labeling and, for a medical device, classify the device. Congress may pass a joint resolution to grant reciprocal marketing approval to a product that the FDA declines to approve through this process. User fees apply to requests for reciprocal marketing approval. The FDA must encourage the sponsors of potentially eligible products to request reciprocal marketing approval.
in studying the non - unique factorization theory of atomic monoids , the development of several invariants such as delta sets @xcite and @xmath4-primality @xcite has provided significant insight . of particular interest is the set of length sets @xmath1 for an atomic monoid @xmath0 , which has as its elements the sets of factorization lengths of elements in @xmath0 @xcite . the following longstanding conjecture states that , with one exception , the set of length sets is a perfect invariant for the important class of _ block monoids _ @xmath5 of zero - sum sequences over a finite abelian group @xmath6 ( * ? ? ? * section 7.3 ) . [ c : introblocklensets ] given two finite abelian groups @xmath6 and @xmath7 with @xmath8 , we have @xmath9 implies @xmath10 . in contrast to the above conjecture , the authors of @xcite show that two distinct numerical monoids ( co - finite , additive submonoids of @xmath11 ) can have the same length sets . in this paper , we investigate the elasticity @xmath12 of elements @xmath13 in a numerical monoid @xmath0 . this invariant , computed as the quotient of the largest factorization length by the smallest , provides a coarse measure of an element s non - unique factorizations . we now state our main result concerning the set @xmath14 of elasticities of @xmath0 . [ t : introelastlencomp ] for distinct arithmetical numerical monoids @xmath15 and @xmath16 , the following are equivalent : 1 . 2 . @xmath18 . therefore , for the class of arithmetical numerical monoids ( numerical monoids generated by an arithmetic sequence ) , the set of elasticities is as strong an invariant as the set of length sets . in contrast , we also provide example [ e : elastlencomp ] , which gives two non - arithmetical numerical monoids with identical sets of elasticities , but distinct sets of length sets . after developing our main result in section [ s : arithmetical ] , we provide a full characterization of the set of elasticities for any numerical monoid , thereby completing a coarser description provided by chapman , holden , and moore @xcite . this characterization ( corollary [ c : elasticityset ] ) demonstrates the stark contrast between the set of length sets , which is often very large and hard to compute , with the set of elasticities , which we describe as a union of monotonically increasing sequences with a common limit point of @xmath3 . for arithmetical numerical monoids , this characterization of @xmath2 takes the form of a complete parametrization ( theorem [ t : arithelastset ] ) . in this section , we provide definitions and previous results related to the elasticity of elements in a numerical monoid . in what follows , let @xmath11 denote the set of non - negative integers . unless otherwise stated , we will assume that @xmath0 has minimal generating set @xmath19 with @xmath20 and @xmath21 . [ d : factorization ] let @xmath22 be a numerical monoid with minimal generating set @xmath19 , and fix @xmath23 . an element @xmath24 is a _ factorization _ of @xmath13 if @xmath25 , and its _ factorization set _ is given by @xmath26 the _ length _ of the factorization @xmath27 , denoted @xmath28 , is given by @xmath29 . for each @xmath13 , the _ length set _ of @xmath13 is the set @xmath30 , and the _ set of length sets _ of the monoid @xmath0 is given by @xmath31 [ r : length ] while the length set of an element in a numerical monoid is a helpful measure of its non - unique factorizations , some information is lost when passing from @xmath32 to @xmath33 . for example , in @xmath34 , the element @xmath35 has as its two distinct factorizations @xmath36 and @xmath37 , both of which have length @xmath38 . thus , even though @xmath39 is singleton , the element @xmath40 has multiple factorizations . this phenomenon is common in numerical monoids , especially those minimally generated by arithmetic sequences of length @xmath41 or greater . see section [ s : arithmetical ] for a more detailed analysis of such monoids . in a numerical monoid , length sets of elements are finite . thus , analyzing the relationship between an element s maximal and minimal lengths provides a meaningful , albeit coarse , gauge of the non - uniqueness of its factorizations . this concept , known as the elasticity of an element , is defined below . [ d : elasticity ] for an element @xmath23 of a numerical monoid , we denote by @xmath42 the _ maximal _ and _ minimal length _ of @xmath13 , respectively . the ratio @xmath43 is called the _ elasticity _ of @xmath13 . when there is no ambiguity , we omit the subscripts and simply write @xmath44 , @xmath45 , and @xmath12 . the _ set of elasticities _ of @xmath0 is given by @xmath46 and the _ elasticity of @xmath0 _ is given by the supremum of this set : @xmath47 . [ d : arithmetical ] a numerical monoid @xmath0 is _ arithmetical _ if it is minimally generated by an arithmetic sequence of positive integers , that is , @xmath48 for positive integers @xmath49 , and @xmath50 . unless otherwise stated , when the generating set of a numerical monoid is expressed in the form @xmath51 , it is assumed that @xmath52 and @xmath53 . we conclude this section by recalling some relevant results from the literature . theorem [ t : holdenmoore ] provides some coarse properties of the set of elasticites of a numerical monoid . proposition [ p : arithminmax ] is a consequence of ( * ? ? ? * theorem 2.2 ) , and characterizes the functions @xmath54 and @xmath55 for any arithmetical numerical monoid @xmath0 . lastly , theorem [ t : setoflengthsets ] appeared as ( * ? ? ? * theorem 3.2 ) and is vital to the proof of corollary [ c : elastlencomp ] . [ t : holdenmoore ] if @xmath0 is a numerical monoid minimally generated by @xmath20 , then @xmath56 is the unique accumulation point of @xmath2 , and there exists an @xmath23 such that @xmath57 . [ p : arithminmax ] fix an arithmetical numerical monoid @xmath15 with @xmath52 and @xmath58 . for @xmath23 , we have the following . a. if @xmath59 for @xmath60 , then @xmath61 . b. if @xmath62 for @xmath63 , then @xmath64 . [ t : setoflengthsets ] fix two distinct numerical monoids @xmath15 and @xmath16 for @xmath65 , @xmath53 and @xmath66 . the following statements are equivalent : a. @xmath67 , and b. @xmath68 , @xmath69 , @xmath70 and @xmath71 . remark [ r : length ] demonstrates that information is lost when passing from @xmath32 to @xmath33 . since only the ratio of @xmath72 and @xmath73 is retained when passing from @xmath33 to @xmath12 , one might expect that further information is lost when passing from the set of length sets @xmath1 to the set of elasticities @xmath2 . while this is true in general ( see example [ e : elastlencomp ] ) , when @xmath0 is an arithmetical numerical monoid , @xmath1 can be recovered from @xmath2 . this is the content of corollary [ c : elastlencomp ] , the main result of this section . for an arithmetical numerical monoid @xmath15 , theorem [ t : setoflengthsets ] states that the values @xmath74 and @xmath75 can both be recovered from @xmath1 , and that if @xmath76 , then @xmath1 can not coincide with @xmath77 for any arithmetical numerical monoid @xmath78 . in order to prove corollary [ c : elastlencomp ] we show that each of these results also holds true for the set of elasticities @xmath2 . the proof of corollary [ c : elastlencomp ] comes in two steps . first , proposition [ p : arithstep ] proves that @xmath74 can be recovered from @xmath2 . this also implies the value of @xmath75 can be recovered ; see remark [ r : arithstep ] . second , theorem [ t : elastlencomp ] ensures that if @xmath79 , then @xmath2 does not coincide with @xmath80 for any arithmetical numerical monoid @xmath81 . [ e : arithelast ] figure [ f : arith_elast_plots ] plots the elasticities of elements of @xmath82 . notice that the graph appears to be a collection of `` slices '' , each consisting of several `` rows '' of points with the same elasticity value . theorem [ t : arithelastset ] uses proposition [ p : arithminmax ] to eliminate much of the redundancy in @xmath2 by reparametrizing in terms of these slices and rows ( definition [ d : elasttuple ] ) , thereby simplifying many computations in results throughout this section . see example [ e : arithelastparams ] for a description of these values . .,width=566 ] [ d : elasttuple ] fix an arithmetical numerical monoid @xmath15 with @xmath52 and @xmath58 . an element @xmath83 is an _ @xmath0-elasticity tuple _ if @xmath84 , @xmath85 , and @xmath86 the value @xmath87 is the _ slice _ of @xmath88 , and @xmath89 is called the _ row _ of @xmath88 . an @xmath0-elasticity tuple @xmath88 is _ minimal _ if @xmath90 and _ maximal _ if @xmath91 . write @xmath92 for the set of @xmath0-elasticity tuples , and define @xmath93 as @xmath94 [ e : arithelastparams ] for arithmetical @xmath15 , each @xmath0-elasticity tuple @xmath88 corresponds to the elasticity @xmath95 occuring in the @xmath96-th slice ( where every elasticity in the 0-th slice is 1 ) . minimal @xmath0-elasticity tuples ( those with a minimal @xmath89 value for their slice ) correspond to the largest elasticity in the slice , and each successive value of @xmath89 corresponds to the next row down in the slice . maximal @xmath0-elasticity tuples play a key role in lemma [ l : extraelast ] and theorem [ t : elastlencomp ] ; see example [ e : extraelast ] . since the tuple @xmath88 corresponds to the @xmath96-th slice , it is tempting to use the ordered pair @xmath97 in place of @xmath88 in definition [ d : elasttuple ] . however , the individual values of @xmath98 and @xmath99 are used in nearly every proof in this section . in particular , the slices whose @xmath0-elasticity tuples have @xmath100 are precisely those whose highest elasticity value is @xmath101 . indeed , the arithmetical numerical monoid @xmath0 depicted in figure [ f : arith_elast_plots ] has @xmath102 , and every third slice has @xmath103 as its highest value . we now state theorem [ t : arithelastset ] , which ensures that the parametrization given in definition [ d : elasttuple ] produces the correct elasticity set . [ t : arithelastset ] @xmath104 for any arithmetical @xmath15 . we begin by showing that for each @xmath23 , the elasticity @xmath105 for some @xmath106 . first , write @xmath107 for @xmath108 , @xmath109 , and @xmath110 . by proposition [ p : arithminmax ] , @xmath64 and @xmath111 , and since @xmath112 , we have @xmath113 by ( * ? ? ? * theorem 3.9 ) . fix @xmath84 and @xmath85 such that @xmath114 , and let @xmath115 . notice that @xmath116 which implies that @xmath117 . since @xmath118 , this means @xmath119 , which yields @xmath120 this means @xmath106 and @xmath121 which proves @xmath122 . conversely , fix @xmath106 . the assumptions on @xmath89 ensure that @xmath123 meaning @xmath124 . fix @xmath125 such that @xmath109 , @xmath110 , and @xmath126 . choosing @xmath127 yields @xmath128 , meaning @xmath129 . in the terminology of example [ e : arithelastparams ] , lemma [ l : elastcomp ] states that increasing an @xmath0-elasticity tuple s slice produces larger elasticities , and increasing its row yields smaller elasticities . [ l : elastcomp ] fix an arithmetical numerical monoid @xmath15 . a. any @xmath130 with @xmath131 satisfy @xmath132 . b. any @xmath133 with @xmath134 satisfy @xmath135 . the claim follows directly upon comparing fractions and observing that @xmath136 for every @xmath106 . we now use the parametrization of @xmath2 provided by theorem [ t : arithelastset ] to prove corollary [ c : elastlencomp ] . we begin with proposition [ p : arithstep ] , which demonstrates how the value of @xmath74 can be recovered from @xmath137 . [ p : arithstep ] fix an arithmetical numerical monoid @xmath15 with @xmath52 and @xmath53 . we have @xmath138 where @xmath139 are the three minimal values in @xmath2 . first , suppose @xmath140 . the maximal @xmath0-elasticity tuple @xmath141 gives @xmath142 by lemma [ l : elastcomp ] . we claim @xmath143 . fix an @xmath0-elasticity tuple @xmath144 with @xmath145 . if @xmath146 , then by lemma [ l : elastcomp ] , @xmath147 . if @xmath148 , then by lemma [ l : elastcomp ] , @xmath149 is minimal when @xmath150 and when @xmath144 is maximal , that is , when @xmath151 . notice that @xmath152 which means @xmath153 subsituting these values for @xmath154 and @xmath155 gives @xmath156 as desired . now , suppose @xmath157 , and let @xmath158 . we will show that @xmath159 and @xmath160 , from which the claim follows directly . indeed , solving the first equality for @xmath161 yields @xmath162 , and substituting into the second yields @xmath163 clearing the denominator on the right hand side yields @xmath164 and dividing by @xmath165 yields the desired equality . by theorem [ t : arithelastset ] , @xmath166 for some @xmath0-elasticity tuple @xmath88 . by lemma [ l : elastcomp ] , @xmath88 is maximal , and since @xmath167 , we have @xmath168 and @xmath169 . this gives the desired form for @xmath154 . it remains to prove that @xmath160 . fix a @xmath0-elasticity tuple @xmath88 and let @xmath170 . by lemma [ l : elastcomp ] , it suffices to assume @xmath88 is maximal . if @xmath171 , then @xmath172 , and if @xmath168 and @xmath169 , then @xmath173 . first , suppose @xmath174 . by lemma [ l : elastcomp ] , we can assume @xmath146 and @xmath100 , meaning @xmath175 . notice that @xmath176 manipulating the above inequality yields @xmath177 which gives @xmath178 now , suppose @xmath179 . by lemma [ l : elastcomp ] , it suffices to assume @xmath168 and @xmath180 , and maximality of @xmath89 gives @xmath181 . notice that @xmath182 manipulating the inequality above yields @xmath183 which gives @xmath184 this completes the proof . [ r : arithstep ] fix an arithmetical numerical monoid @xmath15 . since @xmath185 by theorem [ t : holdenmoore ] , proposition [ p : arithstep ] also implies that we can recover @xmath75 from @xmath2 . [ e : extraelast ] the majority of the proof of theorem [ t : elastlencomp ] considers two arithmetical numerical monoids @xmath15 and @xmath16 satisfying @xmath68 , @xmath69 , @xmath186 , and @xmath70 . in this case , the sets @xmath80 and @xmath2 are nearly identical , as are the elasticities achieved within their respective `` slices '' . figure [ f : arith_missing_elast ] plots the elasticities of @xmath187 and @xmath188 , and the red points mark the ( sparse ) elasticities in @xmath189 . in general , every elasticity that lies in @xmath189 is achieved by a maximal @xmath0-elasticity tuple . lemma [ l : extraelast ] produces an @xmath106 such that @xmath190 , and the proof of theorem [ t : elastlencomp ] verifies that this is the case . ( left ) and @xmath188 ( right).,title="fig:",width=278 ] ( left ) and @xmath188 ( right).,title="fig:",width=278 ] [ l : extraelast ] fix an arithemtical numerical monoid @xmath15 with @xmath52 and @xmath53 , and suppose @xmath70 . write @xmath191 , @xmath192 , and @xmath193 . there exists a maximal @xmath0-elasticity tuple @xmath88 such that a. @xmath194 , and b. @xmath195 . let @xmath99 denote the integer satisfying @xmath196 and @xmath194 , and let @xmath197 denote the value such that @xmath198 is a maximal @xmath0-elasticity tuple . since @xmath186 , there exist integers @xmath199 and @xmath200 such that @xmath201 . notice that @xmath202 so fix @xmath203 such that @xmath204 . for @xmath205 , we have @xmath206 meaning @xmath207 . write @xmath208 for @xmath209 . we see that the @xmath0-elasticity tuple @xmath210 is maximal since @xmath211 and @xmath212 , as desired . [ t : elastlencomp ] if @xmath15 and @xmath16 are distinct arithmetical numerical monoids , then @xmath17 if and only if @xmath68 , @xmath69 , @xmath70 and @xmath71 . if the given conditions are satisfied , then theorem [ t : setoflengthsets ] implies @xmath18 and thus @xmath17 . conversely , if @xmath17 , then @xmath68 by proposition [ p : arithstep ] and @xmath69 by remark [ r : arithstep ] . to complete the proof , it suffices to show that if @xmath68 , @xmath69 , @xmath186 and @xmath70 , then @xmath213 . since @xmath69 , we have @xmath214 and @xmath215 for @xmath191 . define a map @xmath216 given by @xmath217 , where @xmath218 for @xmath209 . notice that @xmath219 since @xmath220 , @xmath221 and @xmath222 we also have @xmath223 , so @xmath224 preserves elasticity values . now , by lemma [ l : extraelast ] , there exists a maximal @xmath0-elasticity tuple @xmath88 satisfying @xmath194 and @xmath195 . if @xmath225 , then it is the image of @xmath226 . in particular , since @xmath227 we must have @xmath228 . moreover , for @xmath229 , if @xmath230 , then @xmath231 by lemma [ l : elastcomp ] , and if @xmath232 , then @xmath233 as the right hand side is not an integer . this means @xmath234 we conclude that the elasticity @xmath235 is only achieved by @xmath88 , which implies @xmath190 and completes the proof . [ c : elastlencomp ] two arithmetical numerical monoids @xmath0 and @xmath81 satisfy @xmath18 if and only if @xmath17 . we conclude this section with example [ e : elastlencomp ] , which shows the `` arithmetical '' hypothesis in corollary [ c : elastlencomp ] can not be omitted . [ e : elastlencomp ] corollary [ c : elastlencomp ] shows that for an arithmetical numerical monoid @xmath0 , computation of the elasticity set @xmath2 ( which is given in theorem [ t : arithelastset ] ) is just as useful as computing the entire set of length sets @xmath1 . this need not be true in general . let @xmath236 and @xmath237 . a simple computation shows that @xmath238 ) = \rho_{s'}(s ' \cap [ 1 , 266]),\ ] ] after which theorems [ t : maxquasi ] and [ t : minquasi ] guarantee that @xmath17 . [ r : elastlencomp ] it remains an interesting question to characterize which numerical monoids @xmath0 and @xmath81 satisfty @xmath239 and @xmath240 . investigating this phenomenon for general numerical monoids or even for specific classes such as those with three minimal generators would be of much interest . while theorem [ t : holdenmoore ] provides a concise description of the maximal elasticity attained in a numerical monoid @xmath0 and a coarse topological property of the set of elasticities of @xmath0 , it does not give a full description of @xmath2 . in this section , we provide such a description by showing that the functions @xmath44 and @xmath45 enjoy a powerful linearity property . we begin with a combinatorial lemma . [ l : subcol ] let @xmath241 , and fix @xmath242 with @xmath243 . there exists @xmath244 satisfying @xmath245 . let @xmath246 for @xmath247 . the sequence @xmath248 has length @xmath249 , so by the pigeonhole principle , @xmath250 for some @xmath251 . this means @xmath252 , so choosing @xmath253 completes the proof . [ t : maxquasi ] given a numerical monoid @xmath22 minimally generated by @xmath20 , the maximal factorization length function @xmath254 satisfies @xmath255 for all @xmath256 . fix a factorization @xmath257 for @xmath13 , and suppose that @xmath258 . since @xmath259 , we have @xmath260 . viewing this sum as @xmath261 integers selected from @xmath262 , lemma [ l : subcol ] guarantees the existence of @xmath263 such that ( i ) @xmath264 for each @xmath265 , ( ii ) @xmath266 , and ( iii ) @xmath267 . this implies @xmath268 , so there exists @xmath269 so that @xmath270 . this gives @xmath271 from which canceling @xmath272 yields @xmath273 . now , suppose that @xmath274 is maximal . the above argument implies that @xmath275 . in particular , if @xmath256 , we must have @xmath276 . this means @xmath277 , so we have @xmath278 , and since @xmath257 has maximal length , we have @xmath279 . this completes the proof . the proof of the following analogous result is almost identical to the proof of theorem [ t : maxquasi ] and hence omitted . [ t : minquasi ] given a numerical monoid @xmath22 minimally generated by @xmath20 , the minimal factorization length function @xmath280 satisfies @xmath281 for all @xmath282 . ( left ) and @xmath45 ( right ) for the numerical monoid @xmath283.,title="fig:",width=278 ] ( left ) and @xmath45 ( right ) for the numerical monoid @xmath283.,title="fig:",width=278 ] [ e : factorizationgraphs ] if a numerical monoid @xmath0 has @xmath272 as its smallest minimal generator then theorems [ t : maxquasi ] and [ t : minquasi ] state that @xmath254 as a function will eventually manifest graphically as a collection of @xmath272 discrete lines with a common slope of @xmath284 . similarly , if @xmath285 is the largest minimal generator , then the graph of @xmath280 will eventually appear as a collection of @xmath285 discrete lines with common slope @xmath286 . figure [ f : fact_plots ] , which shows the functions @xmath44 and @xmath45 for @xmath287 , demonstrates this concept . since the elasticity of an element @xmath13 in a numerical monoid is given by the quotient of @xmath44 and @xmath45 , we use theorems [ t : maxquasi ] and [ t : minquasi ] to provide a characterization of @xmath2 . [ c : elasticityset ] fix a numerical monoid @xmath0 minimally generated by @xmath20 . a. for @xmath288 , we have @xmath289 b. the set @xmath2 is the union of a finite set and a collection of @xmath290 monotone increasing sequences , each converging to @xmath291 . part ( a ) follows directly from theorems [ t : maxquasi ] and [ t : minquasi ] . from this , it follows that for @xmath292 , the sequence @xmath293 is monotone increasing and converges to @xmath291 . this completes the proof . [ r : elasticities ] theorem [ t : holdenmoore ] states that the only accumulation point of the elasticity set @xmath2 is its maximum . corollary [ c : elasticityset ] , on the other hand , gives a characterization of the entire set @xmath2 , from which several other results from @xcite can be recovered . in particular , the characterization of the set of elasticities provided in corollary [ c : elasticityset ] describes @xmath2 as a union of a finite set and @xmath290 monotone increasing sequences , each converging to @xmath291 , which clearly implies that the only accumulation point is @xmath291 . ( left ) and @xmath294 ( right).,title="fig:",width=278 ] ( left ) and @xmath294 ( right).,title="fig:",width=278 ] [ e : rho_plots ] the elasticity graphs for numerical monoids @xmath295 and @xmath294 are given in figure [ f : elast_plots ] . the latter of numerical monoids is not arithmetical and demonstrates that the uniformity of the `` slices '' enjoyed by arithmetical numerical monoids is not present , especially for smaller values . regardless , for any numerical monoid @xmath22 , the characterization of @xmath2 provided in corollary [ c : elasticityset ] shows that @xmath296 can be eventually described as @xmath290 monotone increasing sequences that limit to @xmath291 , where each sequence contains precisely one point in each `` slice . '' the authors would like to thank dr . scott chapman , alfred geroldinger , and sherilyn tamagawa for various helpful conversations and insights . the third author is funded by national science foundation grant dms-1045147 .
in an atomic , cancellative , commutative monoid @xmath0 , the elasticity of an element provides a coarse measure of its non - unique factorizations by comparing the largest and smallest values in its set of factorization lengths ( called its length set ) . in this paper , we show that the set of length sets @xmath1 for any arithmetical numerical monoid @xmath0 can be completely recovered from its set of elasticities @xmath2 ; therefore , @xmath2 is as strong a factorization invariant as @xmath1 in this setting . for general numerical monoids , we describe the set of elasticities as a specific collection of monotone increasing sequences with a common limit point of @xmath3 .
random matrix theory ( rmt ) , @xcite , @xcite has found much success as phenomenological models describing a wide variety of physical systems , from discretization of moduli space @xcite , to the statistics of the cells in the skin of a cucumber @xcite . rmt is the study of eigenvalues derived from random ensembles of matrices with stochastic elements specified by a probability density , @xmath1 , in the space of matrices . most interest is in examining the properties of the eigenvalues induced from the transformation to the eigenvalue basis . early work consisted of using real symmetric , hermitian , unitary , and real quarternion matrices @xcite . the eigenvalues of which are either real or unimodular , ( and termed one dimensional eigenvalues here ) . recently several groups have begun to consider physical applications of matrix models composed of complex matrices . introduced in the early sixties by ginibre @xcite it took decades for others to consider applications . as the probability distribution is not invariant under similarity transformations the diagonalizing parameters must be integrated out by brute force . it was found that only a distribution with a gaussian weight ( ginibre ensemble ) could be solved . the ginibre ensemble was later found to exhibit cubic eigenvalue repulsion in the complex plane , @xcite @xcite . such models are of interest in characterizations of quantum chaos . cubic quasi - energy level repulsion is a key signature of classical chaos within a quantum dissipative system , as defined by haake @xcite . normal matrices are discussed in most matrix theory texts , ( see @xcite , @xcite ) . defined by the sole constraint that they commute with their adjoint , they have the property of being the most general matrix that can be diagonalized by a unitary transformation . the normal matrix model was first introduced in showing how the laughlin wavefunction could be modeled by it and offered some generalizations to inhomogeneous fields @xcite . in @xcite the statistics of eigenvalues of random normal matrices were first explored . in this paper the universality of cubic eigenvalue repulsion in the complex plane for ensembles of random normal matrices will be shown . in section ii the probability distribution in the space of matrices , all correlation functions , and the eigenvalue densities will be obtained . in section iii the level spacing statistics of the eigenvalues obtained will be derived . the term level spacing is borrowed from the wigner - dyson ensembles and will represent here the spacing in the complex plane . in section iv eigenvalues of numerical generated normal matrices will be studied and compared to the analytical results . we begin by defining the joint probability distribution ( jpd ) within the space of normal matrices , @xmath2.\end{aligned}\ ] ] only potentials which are hermitian will be considered , @xmath3 . as a result the joint probability distribution for the eigenvalues will be rotationally symmetric in the complex plane . normal matrices are the most general matrices which can be diagonalized by a unitary transformation , @xmath4 , so that the measure and the weight are invariant . thus it is simple to derive the jacobian for the transformation to the eigenvalues . proceeding analogously to the hermitian matrix case @xcite , the metric in the space of normal matrices is defined as , @xmath5 \nonumber \\ & = & tr(\bf{ud(u^{\dag}zu)u^{\dag}ud(u^{\dag}z^{\ast}u)u^{\dag}})\nonumber \\ & = & tr(\bf{[ds , z][ds , z^{\ast}]}+(\bf{[ds , z]dz^{\ast } } + \bf { dz[ds , z^{\ast } ] } ) + \vert \bf{dz}\vert^2 ) \nonumber \\ & = & c \sum_{i < k}\vert ds_{ik}(z_k - z_i)\vert^2 + \sum_i \vert dz_i\vert^2 , \end{aligned}\ ] ] where @xmath6 is antihermitian and @xmath7 is an overall constant . using the standard riemannian volume form with this metric we get , @xmath8 where @xmath9 is the volume of the unitary group @xmath10 , and @xmath11 is the well known van der monde determinant , latexmath:[\ ] ] where @xmath87 . under the optimization algorithm it is found that many eigenvalues `` leak '' out into the complex plane . adding a further constraint to keep the eigenvalues within a radius of @xmath88 lengthens the generation time dramatically . therefore , for this preliminary study the eigenvalues were `` pruned '' , those falling outside @xmath89 were neglected , ( the number was choosen so that edge effects would be eliminated as well ) . overall , about one third of the eigenvalues were pruned . the results are displayed in figure [ fig : num6 ] . the slight deviation of the numerical and analytical results for large @xmath90 is due to the leakage of eigenvalues . the small @xmath90 behavior is not affected by the leakage . it is found that changing the initial conditions has little effect on @xmath91 . it is also observed that lowering the the threshold for the error function by a factor of ten has a negligible effect . it has been shown that cubic repulsion of eigenvalues obtained from random normal matrices experience a minimum of cubic repulsion in the complex plane . even though normal matrices are subsets of complex matrices we have demonstrated that gaussian normal matrix models yield the same results as the ginibre ensemble of complex matrices . one can define ensembles of complex matrices with weights invariant under similiarity transformations , ( see appendix b of @xcite ) . these ensembles will fall under the @xmath92 and experience a minimum of quartic repulsion . ( getting analytical results for the statistics of the eigenvalues is difficult however ) . ensembles of complex matrices with weight functions invariant under unitary transformations other than the gaussian are not factorable and are not amenable to analytical analysis . for normal matrices we can define identical ensembles to complex models invariant under similiarity transformations and as well define a wide range of ensembles invariant under unitary transformations , ( as demonstrated in this paper ) . the special case of real normal matrices was also shown to experience cubic repulsion in the complex plane . as well , there are even more significant differences between random normal matrices and , more traditional , random matrix models composed of hermitian , unitary , and real symmetric matrices , themselves being subsets of normal matrices . although numerical generation of normal matrices is not as straightforward as for other types of matrices we have shown that analytical results are often much easier to obtain . what numerical information we could obtain does agree with the theoretical result . it is a little disappointing that universality , in the sense of brezin and zee @xcite , is not found for normal matrix models . the simple scaling arguments that lead to universal kernels for other types of matrices do not work here . it may be possible to rescale @xmath90 to obtain a universal spacing distribution @xmath93 . this allows the potential of analytically exploring the statistics of complex eigenvalues which was not possible before . another interesting feature is the closed form expressions for the two point correlation functions in nge , laguerre ( @xmath94 ) , and legendre ensembles in the infinite matrix limit , ( see table [ table ] ) . in terms of physical applications it should be noted that results using the ginibre ensemble of complex matrices can be duplicated with the normal gaussian ensemble . such work includes , modeling cellular structures by le caer and ho @xcite , two dimensional quantum gravity by morris @xcite , and haake s work on generators of quantum dynamics for systems with dissipation @xcite . it has recently been shown , @xcite , that haake s generator of dissipation , @xmath95 , in @xcite @xcite , is properly represented by a normal matrix rather than a complex one . this result strengthens the idea that the eigenvalues of these generators universally exhibit cubic repulsion when dissipative dynamics is present . the results obtained in this work give a more complete picture of the statistics of eigenvalues from random matrices . the normal matrix model , a link between the dyson ensembles and the ginibre ensemble , has a rich structure where interesting results can still be found . 99 email address : [email protected] wigner , e.p . ann.math * 53 * , p36 ; + wigner , e.p . ann.math . * 62 * , p.548 . mehta , m.l . , _ random matrices _ , 2nd edition , ( academic press , 1991 ) . m. kontsevich , funk.anal . i ego pril . , * 25 * , ( 1991 ) , p50 . g. le caer , j.s . ho , j.phys.a : math.gen , * 23 * , 3279 ( 1990 ) . dyson , f , jnl . phys . * 3 * , 140 , ( 1962 ) . j. ginibre , jnl . * 6 * , ( 1965 ) , p440 . f. haake , _ quantum signatures of chaos _ , ( springer verlag , berlin 1991 ) . mehta , m.l . , _ matrix theory ; selected topics and useful results _ , ( editions de physique , les ulis , ( 1989 ) ) ; + deif , a.s . , _ advanced matrix theory for scientists and engineers _ , abaccus press , turnbridge wells , ( 1982 ) . macklin , am.j.phys . , * 52 * , 513 ( 1984 ) . chau , y. yue , phys . a * 167 * , 452 ( 1992 ) . g. oas , phd . thesis , uc davis , march 1995 . tracy , c. , widom , h. _ introduction to random matrices _ , in _ `` geometrical and quantum aspects of integrable systems '' _ , helminick , g.f . , lecture notes in physics , * 424 * , springer - verlag ( berlin ) , 1993 , p103 - 130 . m.v . berry , proc . r. soc , a * 356 * , p375 , ( 1977 ) ; + m.v . berry , proc . r. soc , a * 349 * , p101 , ( 1976 ) ; + o. bohigas , m. giannoni , c. schmit , phys . * 52 * , 1 ( 1985 ) . brezin , zee , a. , t. morris , nucl.phys . * b356 * ( 1991 ) , p703 . g. oas , _ signatures of quantum chaos for dissipative systems _ , submitted to prl . grobe , r. , haake , f. , prl * 62 * , 2893 , ( 1989 ) . .ensembles of random normal matrices defined by their probability distribution . also shown are the corresponding eigenvalue density and two point function . for the nge , laguerre @xmath94 , and legendre ensembles the closed form large @xmath32 result has been shown . [ cols= " < , < , < , < " , ]
random matrix models consisting of normal matrices , defined by the sole constraint @xmath0=0 $ ] , will be explored . it is shown that cubic eigenvalue repulsion in the complex plane is universal with respect to the probability distribution of matrices . the density of eigenvalues , all correlation functions , and level spacing statistics are calculated . normal matrix models offer more probability distributions amenable to analytical analysis than complex matrix models where only a model with a gaussian distribution are solvable . the statistics of numerically generated eigenvalues from gaussian distributed normal matrices are compared to the analytic results obtained and agreement is seen .
AP Lebanese protesters attack American fast food restaurants after Friday prayers in the northeastern city of Tripoli, Lebanon, on Sept. 14. AFP - Getty Images Lebanese men ransack American fast food chains Hardee's and KFC as they protest against the controversial film "Innocence of Muslims" in the northern Lebanese city of Tripoli on Sept. 14. NBC News staff and wire reports -- Protesters in a number of countries across the Muslim world vented anger against the West on Friday as the controversy over an anti-Islamic film raged, with a KFC restaurant torched in Lebanon, violent attacks on U.S. embassies in Sudan and Tunis and fierce protests in Egypt, Jordan and Pakistan. U.S. embassies and consulates are braced for trouble on the Muslim day of prayer, when demonstrations are often held, following the attack on the consulate in Benghazi, Libya, which killed U.S. Ambassador Christopher Stevens and three other Americans. Continue reading. Related links: AFP - Getty Images Lebanese security forces fire shots to disperse men ransacking American fast food chains Hardee's and KFC as they protest against the controversial film "Innocence of Muslims" in the northern Lebanese city of Tripoli on Sept. 14. Reuters Hundreds of protesters set alight a Kentucky Fried Chicken and a Hardee's restaurant in the northern Lebanese city of Tripoli on Sept. 14, witnesses said, chanting against the pope's visit to Lebanon and shouting anti-American slogans. Follow @NBCNewsPictures Sign up for the NBCNews.com Photos Newsletter ||||| The White House asked YouTube on Tuesday to review an anti-Muslim film posted to the site that has been blamed for igniting the violent protests this week in the Middle East. Tommy Vietor, spokesman for the National Security Council, said the White House has "reached out to YouTube to call the video to their attention and ask them to review whether it violates their terms of use." However, the video remained on the site as of Friday afternoon, and it is posted many other places on the Internet. Messages to YouTube, and Google, which owns the site, were not immediately returned Friday. On Wednesday, a YouTube spokesperson said the video "is clearly within our guidelines and so will stay on YouTube." The spokesperson added, however, that the site restricted access in Libya and Egypt because of the unrest. "We work hard to create a community everyone can enjoy and which also enables people to express different opinions. This can be a challenge because what's OK in one country can be offensive elsewhere," the spokesperson said. The video, a trailer for what the promoters say is full-length film produced in the United States, has been cited as a cause for the some of the violent unrest in several Middle Eastern countries, including Egypt and Yemen. White House Press Secretary Jay Carney said Friday that investigators have no evidence that the protests were caused by anything other than the video. "It is in response to a video, a film, that we have judged to be reprehensible and disgusting," Carney said. "That in no way justifies any violent reaction to it, but this is not a case of protest directed at the United States writ large or at U.S. policy. This is in response to a video that is offensive and -- to Muslims. Again, this is not in any way justifying violence. And we've spoken very clearly out against that and condemned it. And the president is making sure in his conversations with leaders around the region that they are committed, as hosts to diplomatic facilities, that -- to protect both personnel and buildings and other facilities that are part of the U.S. representation in those countries."
– Violent protests continued across the Arab world today and claimed at least seven lives, three of them near the US embassy in Sudan's capital city, NBC News reports. Security officers in Khartoum fired tear gas at about 5,000 angry demonstrators, who were also protesting at nearby British and German embassies. In other developments: Two demonstrators were killed and at least 29 injured outside the US embassy in Tunisia, where angry crowds gathered after setting fire to the American School. At least one person died and 25 others were hurt in the Lebanese city of Tripoli, where protesters torched and ransacked a KFC and a Hardee's restaurant, NBC News reports. Demonstrations there were timed to concur with a 3-day visit by Pope Benedict XVI, according to Lebanese officials. A protester died of birdshot wounds during a battle with police near Cairo's US embassy. He was the first Egyptian fatality during the riots. A large demonstration is underway outside the BMCI bank in Nouakchott, the capital of Mauritania, Huffington Post reports. The White House has asked YouTube to review—but not remove—the anti-Muslim video that apparently sparked the rioting, the Washington Post reports. Administration officials asked "them to review whether it violates their terms of use," said a National Security Council spokesman. (YouTube has already removed the video in protesting countries.) See our earlier roundups on the protests, including a no-fly zone in Benghazi and Marines arriving in Yemen.
the photogalvanic effect ( pge ) , predicted independently by @xcite for bulk semiconductors , is characteristic for gyrotropic materials and was recently intensively studied , both theoretically and experimentally , in zinc - blende and diamond - lattice quantum well ( qw ) structures @xcite . in such systems a photocurrent flows under illumination with circularly polarized light which changes its direction if the helicity of the circular polarization is reversed . however , in the presence of a magnetic field a photocurrent can flow even if the light is unpolarized @xcite . this will be denote as magneto - gyrotropic pge below . the effect is due to the fact that the gyrotropic point - group symmetry makes no difference between components of polar and axial vectors and therefore feature currents @xmath1 with @xmath2 the light intensity and @xmath3 the applied magnetic field . here , the proportionality constant is an invariant . the magneto - gyrotropic pge occurring under linearly polarized irradiation in an applied magnetic field has been studied theoretically in bulk crystals and nanostructures @xcite . experimentally the effect was observed in qw structures @xcite , because the point groups @xmath4 and @xmath0 of ( 001)-grown symmetrical and asymmetrical qws belong to gyrotropic classes . so far the magneto - gyrotropic photocurrent has been observed for direct optical transitions . a photocurrent caused by transitions between spin branches of the electron subband splitted due to the rashba effect has been measured in a gasb / inas single qw structure ( wavelength @xmath5 = 385 @xmath6 m or @xmath7 = 3.2 mev ) @xcite . a magnetic field induced photocurrent due to direct inter - band transitions has also been observed in gaas / algaas qws in the spectral range 0.7 @xmath6 m @xmath8 @xmath6 m and was attributed to the magnetic field induced spin - independent asymmetry of the electron dispersion in an asymmetric heterostructure @xcite . here we report on the observation of the magneto - gyrotropic photocurrent in @xmath9-doped inas qws under intra - subband absorption ( _ indirect drude - like transitions _ ) of linearly and circularly polarized far - infrared radiation ( @xmath5 = 148 @xmath6 m and @xmath5 = 90 @xmath6 m ) . the experimental results show that , in the samples under study , the magneto - gyrotropic photocurrent has a spin - related nature . the experiments are carried out on ( 001)-oriented @xmath9-type inas / al@xmath10ga@xmath11sb heterostructures having @xmath0 point symmetry . single qws of 15 nm width with free carrier densities of about @xmath12 @xmath13 and mobility @xmath14 @xmath15/(vs ) ( data are obtained at room temperature ) were grown by molecular - beam epitaxy . several samples of the same batch were investigated at room temperature yielding the same results . the samples have two pairs of ohmic contacts at the corners corresponding to the @xmath16 directions , @xmath17 $ ] and @xmath18 $ ] , and two additional pairs of contacts centered along opposite sample edges with connecting lines along @xmath19 $ ] and @xmath20 $ ] ( see insets in figs . [ fig1]-[fig4 ] ) . an external magnetic field @xmath3 up to @xmath21 t was applied parallel to the interface plane . a pulsed optically pumped far - infrared laser was used for optical excitation @xcite . with nh@xmath22 as active gas 40 ns pulses with about 10 kw power have been obtained at the wavelengths 148 @xmath6 m and 90 @xmath6 m . the far - infrared radiation induces free carrier absorption ( drude - like ) in the lowest conduction subband @xmath231 because the photon energies are smaller than the subband separation and much larger than the @xmath24-linear spin splitting . the samples were irradiated along the growth direction by linearly or circularly polarized radiation . in all experiments the electric field vector of linearly polarized radiation was oriented perpendicularly to the magnetic field direction . circular polarization was obtained by using a crystalline quartz @xmath25 plate . the helicity @xmath26 of the incident light was varied according to @xmath27 , where @xmath28 is the angle between the initial plane of linear polarization and the optical axis of the @xmath25 plate . @xmath26 is equal to @xmath29 for left - handed circularly polarized light @xmath30 and @xmath31 for right - handed polarization @xmath32 . the photocurrent @xmath33 was measured at room temperature in unbiased structures via the voltage drop across a 50 @xmath34 load resistor in a closed circuit configuration . by irradiating the qws with normal incident _ linearly _ polarized light ( see inset in fig . [ fig1 ] ) a fast photocurrent signal has been observed after applying an in - plane magnetic field . the signal follows the temporal structure of the laser pulse intensity , and the polarity of the current changes upon reversal of the applied magnetic field . the results obtained for @xmath35 m and for @xmath36 m are qualitatively the same and differ only by a factor . therefore below we present only data obtained for radiation with @xmath36 m . for @xmath37 aligned along a @xmath38 axis only a transverse effect , i.e. current flow in the direction perpendicular to the applied magnetic field , was detected ( see triangles in figs . [ fig1 ] and [ fig2 ] ) . for another experimental configuration , @xmath39 , both longitudinal and transverse currents were observed , depicted in fig . [ fig3 ] . in the absence of a magnetic field the signals vanish for all directions . this is the case for _ linear _ as well as _ circular _ polarization . a magnetic field induced current has also been observed upon excitation with _ circularly _ polarized radiation . however , the orientation of the current with respect to the direction of the magnetic field and crystallographic axes is completely different . while for @xmath40 absorption of _ linearly _ polarized light results in a photocurrent perpendicular to the magnetic field direction only , the excitation by _ circularly _ polarized radiation yields a current in both directions , normal and parallel to the magnetic field ( figs . [ fig1 ] and [ fig2 ] ) . the current component normal to the magnetic field , applied along @xmath20 $ ] , is independent of the radiation helicity and coincides with that induced by _ linearly _ polarized radiation ( fig . [ fig1 ] ) , say @xmath41 where @xmath2 is the intensity of the radiation . this observation indicates that the origin of this current is the same for both _ linearly _ and _ circularly _ polarized radiation . in contrast , the current along the magnetic field direction changes its sign upon changing the helicity from right- to left - handed and vanishes for _ linearly _ polarized radiation : @xmath42 ( see fig . [ fig2 ] ) . this current has been observed previously @xcite and is caused by the spin - galvanic effect due to optical orientation of carriers and the larmor precession of electron spins . if the magnetic field is applied along one of the cubic axes , say @xmath43 , the current generated by irradiation with helicity @xmath26 may be described by the empirical formula @xmath44 and can be detected for both directions @xmath45 $ ] and @xmath18 $ ] ( see fig . [ fig4 ] ) . in this equation @xmath46 and @xmath47 are constants of the same order of magnitude . the helicity dependent component of the current determined by @xmath47 is caused in this geometry by the spin - galvanic effect superimposed on a helicity independent contribution given by @xmath46 . in the linear approximation in the magnetic field strength @xmath37 the magnetic field induced photogalvanic effect is phenomenologically given by @xmath48 where the first term on the right hand side gives the magneto - gyrotropic photogalvanic effect and the second term is the magnetic field induced spin - galvanic effect . in this equation , @xmath49 is the electric field of the radiation with @xmath50 , where @xmath51 is the real amplitude of the field and @xmath52 denotes a complex polarization vector of unit length , @xmath53 . @xmath54 is the symmetrized product of the electric field with its complex conjugate @xmath55 the vector @xmath56 is the unit vector pointing in the direction of light propagation . the fourth rank tensor @xmath57 is symmetric in the last two indices . it is a pseudo - tensor whereas @xmath58 is a regular third rank tensor . while the second term on the right hand side of eq . ( [ phen0 ] ) requires circularly polarized radiation the first term may be non - zero even for unpolarized radiation . in the following we consider ( 001)-oriented quantum wells based on iii - v@xmath59compounds . the symmetry of these quantum wells may belong to the point groups @xmath4 or @xmath0 depending , respectively , on equivalence or non - equivalence of the qw interfaces . the present experiments have been carried out on @xmath0 structures and , therefore , we will discuss this symmetry only . in order to describe the experiments it is convenient to use both cartesian coordinate systems introduced above . in the coordinate system @xmath60 $ ] , @xmath20 $ ] , @xmath61 $ ] , the in - plane axes lie in the crystallographic planes @xmath62 and @xmath63 which are the mirror reflection planes containing the two - fold axes of @xmath0 . in this coordinate system eq . ( [ phen0 ] ) can be reduced to @xmath64 in the crystallographic directions @xmath45 , y \parallel [ 010]$ ] , eqs . ( [ phen ] ) are rewritten as @xmath65 @xmath66 @xmath67 where @xmath68 ( @xmath69 ) . in these equations we set for the intensity @xmath70 . the parameters @xmath71 to @xmath72 , @xmath73 to @xmath74 and @xmath75 to @xmath76 expressed by the non - zero elements of the tensors @xmath57 and @xmath58 allowed in @xmath0 symmetry are given in table [ t1 ] and table [ t1a ] , respectively . equations ( [ phen ] ) show that the first terms on the right hand side ( parameters @xmath77 ) yield a current in the plane of the quantum well which is proportional to the intensity @xmath2 and independent of the state of radiation polarization . this current is induced even for unpolarized radiation . in the case of the second and third terms linear polarization is needed in order to give a photocurrent . the photocurrent assumes a maximum for light polarized along @xmath78 or @xmath79 in the case of the second terms described by the parameters @xmath80 or along the bisector of @xmath78 and @xmath79 for the third terms proportional to @xmath81 . thus , these terms do not contribute to the current if the radiation is circularly polarized . the last terms in eqs . ( [ phen ] ) describe a current proportional to the helicity of radiation being maximum for left- or right - handed circular polarization and changing sign when the helicity @xmath26 is switched from @xmath82 to @xmath83 . at normal incidence of radiation in all cases a magnetic field in the plane of the quantum well is required to obtain a current . at zero magnetic field no current is allowed at normal incidence of radiation in the present @xmath0 point group symmetry case and , in fact , it does not occur in experiment . the relations between polarization and magnetic field after eqs . ( [ phen ] ) and eqs . ( [ phena ] ) are summarized in table [ t2 ] . .definition of the parameters @xmath84 and @xmath85 ( @xmath86 ) in eqs . ( [ phen ] ) in terms of non - zero components of the tensors @xmath57 and @xmath58 for coordinates @xmath87 $ ] , @xmath88 $ ] and @xmath89 $ ] . @xmath0 symmetry and normal incidence of radiation along @xmath90 is assumed . [ cols=">,<,>,<",options="header " , ] now we analyze the phenomenological eqs . ( [ phen ] ) with respect to experiments . three magnetic field orientations were applied , namely , @xmath91 , @xmath92 , and @xmath93 . note that due to @xmath0 point group symmetry the geometry @xmath94 is same to that for @xmath95 , however , @xmath92 and @xmath91 are not equivalent . we discuss the electric current parallel and normal to the magnetic field in each case for three states of polarization : _ linear _ as well as left- and right - handed _ circular_. in the experiments with _ linear _ polarized radiation the electric field vector is always oriented normally to @xmath37 . * @xmath91 ( figs . [ fig1 ] and [ fig2 ] ) : + in this configuration we find that strength and sign of the current measured in the direction normal to the magnetic field , @xmath96 , is the same for all three states of polarization ( for _ linear _ polarization in this case @xmath97 , @xmath98 ) as shown in fig . [ fig1 ] . this allows us to conclude that the current in this geometry in our samples is dominated by the first term in eqs . ( [ phen ] ) , @xmath99 , while the second term is negligible , @xmath100 . thus , the observed magneto - gyrotropic effect is represented by a polarization - independent magnetic field induced photocurrent . the current along @xmath101 appears also , but for _ circular _ polarization only . it has the same magnitude for right- and left - handed _ circular _ polarization but changes sign if the helicity is switched from @xmath32 to @xmath30 and vanishes for _ linear _ polarization ( see fig . [ fig2 ] ) . this is due to the spin - galvanic effect described by the last term in eqs . ( [ phen0 ] ) and ( [ phen ] ) . * @xmath92 : + qualitatively we have the same situation as described above if we exchange @xmath96 and @xmath101 . the current densities , however , differ quantatively . the magnitude of the photocurrent parallel to the magnetic field and caused by _ circularly _ polarized radiation is smaller than that in the above case @xmath91 . helicity independent _ and perpendicular to @xmath37 current is , in contrast , also different , but it exeeds that in the previous configuration . this difference in photocurrents is due to the fact that for @xmath0 point symmetry the axes @xmath102 $ ] and @xmath103 $ ] are non - equivalent which is taken into account in eqs . ( [ phen ] ) by introducing independent parameters @xmath84 and @xmath85 ( @xmath104 ) . * @xmath93 or @xmath105 ( figs . [ fig3 ] and [ fig4 ] ) : + for an orientation of the magnetic field parallel to one of the two in - plane @xmath106 axes of the material we find for _ linearly _ polarized radiation current components not only perpendicular but , in contrast to the previous magnetic field orientations , also parallel to @xmath37 as displayed in fig . [ fig3 ] . for _ circularly _ polarized radiation we observe also the spin - galvanic current at contact pairs with connecting lines parallel and normal to the magnetic field . the spin - galvanic effect manifests itself by a difference of the strength of the current for left- and right - handed _ circular _ polarization . the spin - galvanic current is superimposed on the helicity independent magneto - gyrotropic current ( fig . [ fig4 ] ) . & & + & & & & + ' '' '' & @xmath107 & 0 & 0 & @xmath108 & @xmath109 + ' '' '' [ -3ex ] @xmath110 & @xmath111 & @xmath112 & @xmath113 & 0 & 0 + ' '' '' & @xmath114&@xmath115 & @xmath116 & 0 & 0 + ' '' '' [ -3ex ] @xmath117 & @xmath118 & 0 & 0 & @xmath119 & @xmath120 + ' '' '' & @xmath121 & @xmath122 & @xmath123 & @xmath124 & @xmath125 + ' '' '' [ -3ex ] @xmath126 & @xmath127 & @xmath128 & @xmath129 & @xmath130 & @xmath131 + ' '' '' & @xmath121 & @xmath132 & @xmath133 & @xmath134 & @xmath135 + ' '' '' [ -3ex ] @xmath136 & @xmath137 & @xmath138 & @xmath139 & @xmath140 & @xmath141 + in general , the observed magneto - gyrotropic pge descibed by the parameters @xmath142 in eqs . ( [ phen ] ) can be attributed to three possible mechanisms , two of them being spin - dependent and one spin - independent or diamagnetic . here , we briefly characterize all , present qualitative estimations for each and discuss which mechanism is most likely responsible for the magneto - gyrotropic photocurrent observed in the samples under study . in the first mechanism the electric current appears due to an asymmetry of spin - dependent _ spin - conserving _ energy relaxation processes in a system of hot carriers heated by free carrier absorption @xcite . due to the zeeman spin splitting of electron spin states in the magnetic field , say @xmath143 , the difference in population of the spin branches @xmath144 is given by the ratio @xmath145 , where @xmath146 is the electron @xmath146-factor , @xmath147 is the bohr magneton , and @xmath148 is the average electron energy . the light absorption leads to a non - equilibrium symmetrical distribution of electrons within each spin branch with the average energy different from that in equilibrium . taking into account the gyrotropic symmetry of the qw , the matrix element for scattering @xmath149 of an electron by a phonon can be presented in the form @xmath150 , where @xmath151 @xmath152 as functions of the involved wave vectors have the same parities . thus , the ratio of antisymmetric to symmetric parts of the scattering probability rate @xmath153 is given by @xmath154 . since the antisymmetric component of the electron distribution function decays within the momentum relaxation time @xmath155 , one can write for the photocurrent @xmath156 \right\rangle \sim e \tau_p \frac{r_{xi}}{\hbar p } \frac{g \mu_b b_x}{\bar{e } } \eta i\ : , \label{2}\ ] ] where @xmath23 is the electron charge , @xmath157 is the electron effective mass , @xmath158 is the fraction of the energy flux absorbed in the qw due to all possible indirect optical transitions , and the angle brackets mean averaging over the electron energy distribution . while deriving eq . ( [ 2 ] ) we took into account the balance of energy : @xmath159 where @xmath160 . the contributions to the current from electrons in the branches @xmath161 are of opposite sign . however , they do not compensate each other because of the magnetic - field induced selective occupation of the branches . the next mechanism to be considered is based on the asymmetry of spin - flip processes and represents in fact the spin - galvanic effect described by @xmath162 where @xmath163 is the average electron spin and @xmath164 is its equilibrium value governed by the ratio @xmath165 . the observation of the spin - galvanic effect @xcite was carried out under conditions where @xmath164 was negligible . then the spin - galvanic current is generated as a result of the spin relaxation which tends to depress the polarization . the same is relevant to the helicity - dependent photocurrent described by the coefficients @xmath47 in eq . ( [ 1 ] ) . a possible contribution of the spin - galvanic effect to the polarization - independent photocurrent can be interpreted as a light - induced depolarization of the electronic spins followed by the spin relaxation tending to restore the polarization to @xmath164 . as well as in @xcite the asymmetry of spin - flip processes can be related to the @xmath166-linear terms in the electron effective hamiltonian , @xmath167 , where the coefficients @xmath168 and @xmath169 represent the bulk- and structure - inversion asymmetry . applying the same reasons as in @xcite one can estimate the spin - galvanic contribution to the magneto - gyrotropic photocurrent as @xmath170 here @xmath171 is a factor describing the depolarization of electron spin under photoexcitation followed by energy relaxation . it can be estimated as @xmath172 , where @xmath173 is the time of electron energy relaxation governed mainly by electron - electron collisions , and @xmath174 is the spin relaxation time . assuming the times to be @xmath175 and @xmath176 for the room temperature , the factor @xmath171 can be estimated as @xmath177 . finally , the diamagnetic mechanism is related to spin - independent magnetic field induced @xmath166-linear terms , @xmath178 , in the electron hamiltonian , where @xmath179 and @xmath180 is the center of mass of the electron envelope function in the @xmath181-th subband @xcite . in an asymmetrical qw , @xmath182 are nonzero and the subband dispersion is given by parabolas with their minima ( or maxima in case of the valence band ) shifted from the origin @xmath183 by values proportional to the in - plane magnetic field . one can show that the diamagnetic mechanism contributes to the photocurrent under indirect intra - subband optical transitions only if the indirect transition involves intermediate states in other bands or subbands , @xmath184 . then , the magneto - gyrotropic photocurrent is estimated as @xmath185 where @xmath186 is a linear combination of the constants @xmath187 and @xmath188 in the subband @xmath189 and intermediate band . for intermediate states in the valence band , the parameter @xmath190 is of the order of @xmath191 , and , for intermediate states in the next conduction subband @xmath192 , one has @xmath193 , where @xmath194 is the band gap , and @xmath195 is the @xmath192-@xmath189 energy spacing . it is reasonable to expect the ratios @xmath196 and @xmath197 to be of order of @xmath198 and @xmath199 , respectively . the ratio @xmath200 can be obtained by using the equation for @xmath169 derived in ref . it follows then that , because of the small parameters @xmath171 and @xmath190 , it is the first mechanism that is responsible for the magneto - gyrotropic photocurrent induced in inas / algaas qws under indirect absorption of the far - infrared radiation . in conclusion , it has been shown that in gyrotropic systems the application of an external magnetic field induces in addition to the helicity - sensitive spin - galvanic current a light polarization independent current which we attribute to the magneto - gyrotropic effect . three different microscopic mechanisms that may contribute to this effect have been considered . under steady - state optical excitation , the role of each mechanism in the magneto - gyrotropic photocurrent is established through theoretical estimation . however , the three contributions can be separated experimentally in time - resolved measurements . indeed , after the removal of light or under ultra - short pulsed photoexcitation the magneto - gyrotropic current should decay , for the mechanisms considered above , within the energy ( @xmath173 ) , spin ( @xmath201 ) and momentum ( @xmath155 ) relaxation times , respectively . a photogalvanic detection of the nuclear spin resonance could be another evidence for spin - related mechanisms of the photocurrent . the high quality quantum wells were kindly provided by j. de boeck and g. borghs from imec belgium . we thank l.e . golub for helpful discussion . ivchenko and g.e . pikus , pisma zh . . fiz . * 27 * , 640 ( 1978 ) [ jetp lett . * 27 * , 604 ( 1978 ) ] . belinicher , phys . a * 66 * , 213 ( 1978 ) . ivchenko , usp . nauk * 45 * , 1461 ( 2002 ) [ phys . uspekhi * 45 * , 1299 ( 2002 ) ] . ganichev and w. prettl , j. phys . : condens . matter * 15 * , 935 ( 2003 ) . ivchenko and g.e . pikus , izv . nauk sssr ( ser . fiz . ) * 47 * , 2369 ( 1983 ) [ bull . ussr , phys . * 47 * , 81 ( 1983 ) ] . magarill , fiz . tela * 32 * , 3558 ( 1990 ) [ sov . solid state * 32 * , 2064 ( 1990 ) ] . gorbatsevich , v.v . kapaev , and yu.v . kopaev , pisma zh . . fiz . * 57 * , 565 ( 1993 ) [ jetp lett . * 57 * , 580 ( 1993 ) ] . kibis , physica e * 12 * , 741 ( 2002 ) . ivchenko and b. spivak , phys . b * 66 * , 155404 ( 2002 ) . dmitriev , s.a . emelyanov , s.v . ivanov , p.s . kopev , ya.v . terentev , and i.d . yaroshetskii , pisma zh . fiz . * 54 * , 279 ( 1991 ) [ jetp lett . * 54 * , ( 1991 ) ] . aleshchenko , i.d . voronova , s.p . grishechkina , v.v . kapaev , yu.v . kopaev , i.v . kucherenko , v.i . kadushkin , and s.i . fomichev , pisma zh . 58 * , 377 ( 1993 ) [ jetp lett . * 58 * , ( 1993 ) ] . i.v . kucherenko , l.k . vodopyanov , and v.i . kadushkin , fiz . . poluprovodn . * 31 * , 872 ( 1997 ) [ semiconductors * 31 * , 740 ( 1997 ) ] . ganichev , physica b * 273 - 274 * , 737 ( 1999 ) . ganichev , e.l . ivchenko , v.v . belkov , s.a . tarasenko , m. sollinger , d. weiss , w. wegscheider , and w. prettl , _ nature _ ( london ) * 417 * , 153 ( 2002 ) . t. ando , a.b . fowler , and f. stern , rev . mod . phys . * 54 * , 437 ( 1982 ) . p. pfeffer and w. zawadzki , phys . b * 59 * , 5312 ( 1999 ) .
we investigate both experimentally and theoretically , the magneto - gyrotropic photogalvanic effect in zinc - blende based quantum wells with @xmath0 point - group symmetry using optical excitation in the terahertz frequency range . the investigated frequencies cause intra - subband but no inter - band and inter - subband transitions . while at normal incidence the photocurrent vanishes at zero magnetic field , it is shown that an in - plane magnetic field generates photocurrents both for polarized and unpolarized excitation . in general the spin - galvanic effect , caused by circularly polarized light , and the magneto - gyrotropic effect , caused by unpolarized excitation , is superimposed . it is shown that in the case of two specific geometries both effects are separable .
it is well - known since the mid-1970 s that @xmath0 hyperons produced in unpolarized @xmath6 collisions are to a large degree polarized transversely to the production plane . there have been many experimental and theoretical investigations aimed at understanding this striking polarization phenomenon , but no consensus has been reached about its origin . one of the difficulties in interpreting the available ( mostly fixed target ) data is that they are not or only partially in a region where a factorized description of the cross section is expected to be applicable . high - energy hadron collider data would be very welcome , for instance from rhic , tevatron or lhc , but there the capabilities to measure @xmath0 polarization via the self - analyzing parity violating decay @xmath7 are typically restricted to the midrapidity region , where protons can be identified , but the degree of transverse polarization @xmath8 is expected to be very small . for symmetry reasons @xmath9 at midrapidity in @xmath6 collisions in the center of mass frame . nevertheless , some interesting @xmath0 polarization studies can be done using the process @xmath10 , where the @xmath0 and jets can be in the midrapidity region without paying a suppression penalty . it is especially of interest at lhc , where the asymmetry expressions may take a particularly simple form depending on the importance of gluons . also , transverse @xmath0 polarization measurements at forward rapidities at lhc will be discussed below , as it offers a promising way of extracting the @xmath11 dependence of the saturation scale . these two suggestions will hopefully enhance the interest in @xmath0 polarization measurements at high energy colliders , at lhc in particular . large asymmetries have been observed in @xmath12 @xcite . the main features of the asymmetry are : @xmath13 grows with @xmath14 and @xmath15 ) ; for @xmath16 it becomes flat ( measured up to @xmath17 gev / c ) ; no @xmath18 dependence has been seen . for a comprehensive review of data cf . ref . many qcd - inspired models have been proposed to explain the transverse @xmath0 polarization data . most models give qualitative descriptions of the data for @xmath19 . however , @xmath8 stays large at least until the highest measured @xmath20 gev/@xmath21 . for sufficiently large @xmath22 perturbative qcd and collinear factorization should become applicable . consider for example the @xmath23 subprocess contribution to the @xmath24 cross section in collinear factorization . it is of the form : @xmath25 , where @xmath26 is the quark density in proton 1 , @xmath27 is the gluon density in proton 2 , and @xmath28 is the @xmath0 fragmentation function ( ff ) . in a similar way the transverse polarization should be of the form : @xmath29 , involving the unpolarized parton densities and the unpolarized hard partonic subprocess . the latter because @xmath0 polarization created in the helicity conserving hard partonic scattering is very small , @xmath30 @xcite . the question mark indicates that at leading twist there is no collinear fragmentation function describing @xmath31 for symmetry reasons . in collinear factorization @xmath32 is necessarily power suppressed . dropping the demand of _ collinear _ factorization , does allow for a leading twist solution : the function @xmath33 @xcite for @xmath0 s , depicted in fig . [ d1tperp ] . it describes a nonperturbative @xmath34 dependence in the fragmentation process , which is allowed by the symmetries ( parity and time reversal ) . as the @xmath0 polarization arises in the fragmentation of an _ unpolarized _ quark , the descriptive name `` polarizing fragmentation function '' was suggested for it @xcite . currently @xmath35 is expected to be universal , despite its potential color flow dependence @xcite . @xmath35 has been extracted from fixed target @xmath36 data @xcite . reasonable functions are obtained : @xmath37 has opposite signs for @xmath38 versus @xmath39 quarks , and the latter is larger . this leads to cancellations in order that @xmath40 . this extraction has been done under the restriction of @xmath41 gev/@xmath21 to exclude the soft regime , but also to retain sufficient data to make a fit to . whether this restriction is sufficiently strict to ensure the validity of the description is a matter of concern , due to the large @xmath42 factors required to obtain a cross section description . the validity of the factorized description depends on whether a proper cross section description can be obtained . this requires data at higher @xmath18 and @xmath44 , but not necessarily also at large @xmath45 if one goes beyond @xmath46 . if the origin of the transverse @xmath0 polarization is indeed due to polarizing fragmentation , then another related asymmetry could be observed that does not need to vanish at @xmath47 , namely in the process @xmath48 @xcite . the suggestion is to select two - jet events and to measure the jet momenta @xmath49 and @xmath50 ( with @xmath51 ) , in addition to the momentum @xmath52 and polarization @xmath53 of the @xmath0 that is part of either of the two jets . a single spin asymmetry proportional to @xmath54 can then arise , which is neither power suppressed , nor needs to be zero at midrapidity . in the center of mass frame of the two jets the asymmetry is of the form : @xmath55 the analyzing power @xmath56 of the asymmetry depends on @xmath37 . this new @xmath0+jets observable could allow for a more trustworthy extraction of @xmath37 ( for both quarks and gluons ) and subsequent predictions , for instance for semi - inclusive dis @xcite . at lhc ( and at rhic ) this process @xmath48 can be studied . for instance , alice with its excellent pid capabilities can measure @xmath0 s over a wide @xmath44 range ( for example , in a typical yearly heavy ion collision run at least up to 16 gev/@xmath21 ) . the alice rapidity coverage is @xmath57 . jets can be reconstructed above 30 gev ( up to 250 gev in a typical yearly run ) . if the jet rapidities ( @xmath58 ) are in this kinematic region and if gluon fragmentation is at least as important as quark fragmentation for both unpolarized and polarized @xmath0 production , then the process is dominated by gluon - gluon ( @xmath59 ) scattering holds throughout . furthermore , chiral - odd contributions @xcite will not be considered here . ] : @xmath60 because no model or fit for @xmath61 is available yet , no predictions can be made in this case . if it happens that @xmath62 , then one can use the extracted @xmath63 to obtain an estimate . when gluons still dominate in the denominator , one finds for @xmath64 ( @xmath65 ) @xmath66 \frac{\sum_q f_1^q(x_1)d_{1t}^{\perp\,q}(z{,}k_{\lambda\,t}^2 ) } { f_1^g(x_1 ) d_1^g(z{,}k_{\lambda\,t}^2)}},\ ] ] where @xmath67 , @xmath68 , and @xmath69 . in the considered rapidity interval the prefactor @xmath70 is almost @xmath71 independent . in practice , it may be that @xmath72 is considerably smaller than @xmath73 . in that case the @xmath74 subprocess needs to be taken into account in the denominator of the asymmetry too ( not done l0.6 in @xcite ) . here we will use the dsv fragmentation functions of ref . @xcite which indeed has @xmath75 at larger @xmath76 . the asymmetry is given in fig . [ asymm ] for three different values of the @xmath0 momentum component transverse to the jet direction . for very low values of this @xmath77 the asymmetry at large @xmath76 exceeds -1 , which is unphysical . it signals a problem with the @xmath78-dependence of the function @xmath63 for which it was not properly taken into account that for each value of @xmath77 the positivity bound has to be satisfied @xcite . nevertheless , it may be expected that the result at least has the generic shape for negligible @xmath61 . the asymmetry is quite sensitive to the cancellation between @xmath38 and @xmath39 contributions , like in sidis @xcite , and can even flip its overall sign depending on the amount of @xmath79 breaking in the unpolarized fragmentation functions ( dsv assumes @xmath79 symmetry ) . more reliable estimates are not possible at this stage . alice would have most data in the region @xmath80 and would therefore provide valuable information on gluonic contributions to @xmath37 . @xmath0 polarization is also very interesting in @xmath81 reactions at very high @xmath18 , large @xmath82 and @xmath83 . in that kinematic regime of small @xmath11 , saturation of the gluon density is expected . the process @xmath84 is sensitive to saturation and could help to determine properties of this phenomenon . none of the existing data is in the saturation regime . at high energy colliders , such as rhic and lhc , protons often can not be identified in the forward direction , which hampers the measurement of @xmath0 polarization . although relatively forward @xmath0 s ( @xmath85 ) in @xmath86 collisions have been identified through event topology @xcite , it is not clear whether the polarization can be reconstructed in this way too , despite the self - analyzing decay property . an alternative may be to use neutral decays @xmath87 ( 50% less frequent than @xmath88 ) . despite being a very challenging measurement , @xmath0 polarization at forward rapidities offers a unique direct probe of gluon saturation in both @xmath6 and @xmath89 collisions at lhc . the saturation scale @xmath90 and even its evolution with @xmath11 could be probed in this way @xcite . the cross section of forward hadron production in the ( near-)saturation regime is schematically of the form : pdf @xmath91 dipole cross section @xmath91 ff @xcite . since @xmath37 is @xmath92-odd , it essentially probes the derivative of the dipole cross section . at transverse momenta of order @xmath90 the dipole cross section changes much , which thus leads to a @xmath90-dependent peak in ( strictly speaking minus ) the @xmath0 polarization . this was first demonstrated in ref.@xcite for the mclerran - venugopalan model @xcite . in this model @xmath90 is a constant , leading to a peak that is @xmath45 independent . more realistically the saturation scale is expected to change with the small-@xmath11 values probed : @xmath93 . models that incorporate this are for instance : the well - known gbw model @xcite , which describes well small-@xmath11 dis data ; the dhj model @xcite , which describes well forward @xmath94 rhic data ; and , the gs model @xcite , which describes well both types of data . in all three models @xmath95 , as indicated by the dis data . here we will restrict to the latter two models . although they have considerable differences ( the gs model is geometrically scaling , the dhj model is not ; the gs model leads to more steeply falling @xmath44 spectra of produced hadrons ) @xcite , both the dhj and gs models lead to the same conclusion about the peak of the @xmath0 polarization : its @xmath45 dependence is to very good approximation the @xmath11 dependence of @xmath90 ! this is shown in fig.[auplot ] for @xmath2 collisions at lhc ( the solid line is the gs model prediction , the dashed line the dhj one ) . in @xmath6 collisions at lhc @xmath90 and hence the @xmath3 position of the peak is slightly lower . at rhic unfortunately the peak is likely situated below 1 gev/@xmath21 , where the formalism can not be trusted . therefore , @xmath0 polarization studies at lhc could prove most interesting . first of all , i thank my various collaborators on this topic . second , i thank gerry bunce and carl gagliardi for useful discussions . part of this research was funded by the `` stichting voor fundamenteel onderzoek der materie ( fom ) '' , which is financially supported by the `` nederlandse organisatie voor wetenschappelijk onderzoek ( nwo ) '' . a. lesnik _ et al . _ , phys . * 35 * 770 ( 1975 ) ; + g. bunce _ et al . _ , phys . rev . lett . * 36 * 1113 ( 1976 ) . a. d. panagiotou , int . j. mod . a5 * 1197 ( 1990 ) . g. l. kane , j. pumplin and w. repko , phys . lett . * 41 * 1689 ( 1978 ) . p. j. mulders and r. d. tangerman , nucl . * b461 * 197 ( 1996 ) . m. anselmino , d. boer , u. dalesio and f. murgia , phys . * d63 * 054029 ( 2001 ) . a. metz , phys . * b549 * 139 ( 2002 ) ; + l. p. gamberg , a. mukherjee and p. j. mulders , phys . rev . * d77 * 114026 ( 2008 ) ; + s. meissner and a. metz , arxiv:0812.3783 [ hep - ph ] ; + f. yuan and j. zhou , arxiv:0903.4680 [ hep - ph ] . d. boer , c. j. bomhof , d. s. hwang and p. j. mulders , phys . lett . * b659 * 127 ( 2008 ) . m. anselmino , d. boer , u. dalesio and f. murgia , phys . * d65 * 114014 ( 2002 ) . y. kanazawa and y. koike , phys . * d64 * 034019 ( 2001 ) & arxiv : hep - ph/0012005 ; + j. zhou , f. yuan and z. t. liang , phys . * d78 * 114008 ( 2008 ) . d. de florian , m. stratmann and w. vogelsang , phys . * d57 * 5811 ( 1998 ) . b. i. abelev _ et al . _ [ star collaboration ] , phys . * c76 * 064904 ( 2007 ) . d. boer and a. dumitru , phys . lett . * b556 * 33 ( 2003 ) . d. boer , a. utermann and e. wessels , phys . * b671 * 91 ( 2009 ) . a. dumitru and j. jalilian - marian , phys . lett . * 89 * 022301 ( 2002 ) . l. d. mclerran and r. venugopalan , phys . * d49 * 2233 & 3352 ( 1994 ) . k. j. golec - biernat and m. wsthoff , phys . * d59 * 014017 ( 1999 ) . a. dumitru , a. hayashigaki and j. jalilian - marian , nucl . * a765 * 464 ( 2006 ) . d. boer , a. utermann and e. wessels , phys . * d77 * 054014 ( 2008 ) .
transverse polarization of @xmath0 hyperons produced in @xmath1 and @xmath2 collisions is discussed . a factorized description in the intermediate to high @xmath3 region is considered that involves transverse momentum and spin dependence in the fragmentation process . consequences and suggestions for investigations at lhc are pointed out for the process @xmath4 at midrapidity and @xmath5 in the forward region .
SECTION 1. ALIENS INELIGIBLE TO RECEIVE VISAS AND EXCLUDED FROM ADMISSION FOR NONPAYMENT OF CHILD SUPPORT. (a) In General.--Section 212(a)(10) of the Immigration and Nationality Act (8 U.S.C. 1182(a)(10)), as redesignated and amended by sections 301(b), 347(a), and 352(a) of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (Public Law 104-208; 110 Stat. 3009-576, 3009-639, 3009-641), is amended by adding at the end the following new subparagraph: ``(F) Nonpayment of child support.--Any alien is inadmissible who is legally obligated under a judgment, decree, or order to pay child support (as defined in section 459(i) of the Social Security Act), and whose failure to pay such child support has resulted in an arrearage exceeding $5,000, until child support payments under the judgment, decree, or order are satisfied or the alien is in compliance with an approved payment agreement.''. (b) Effective Date.--The amendment made by this section shall apply to visas issued on or after 180 days after the date of the enactment of this Act. SEC. 2. REMOVAL OF ALIENS FOR NONPAYMENT OF CHILD SUPPORT. (a) In General.--Section 237(a) of the Immigration and Nationality Act (8 U.S.C. 1227(a)), as redesignated by section 305(a)(2) of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (Public Law 104-208; 110 Stat. 3009-598) is amended by adding at the end the following: ``(7) Nonpayment of child support.--Any alien is deportable who is legally obligated under a judgment, decree, or order to pay child support (as defined in section 459(i) of the Social Security Act), and whose failure to pay such child support has resulted in an arrearage exceeding $5,000, until child support payments under the judgment, decree, or order are satisfied or the alien is in compliance with an approved payment agreement.''. (b) Effective Date.--The amendment made by this section shall take effect 180 days after the date of the enactment of this Act. SEC. 3. ALIENS INELIGIBLE FOR NATURALIZATION FOR NONPAYMENT OF CHILD SUPPORT. (a) In General.--Section 318 of the Immigration and Nationality Act (8 U.S.C. 1429) is amended by adding at the end the following: ``No person shall be naturalized who is legally obligated under a judgment, decree, or order to pay child support (as defined in section 459(i) of the Social Security Act), and whose failure to pay such child support has resulted in any arrearage, until child support payments under the judgment, decree, or order are satisfied or the alien is in compliance with an approved payment agreement.''. (b) Effective Date.--The amendment made by this section shall apply to applications for naturalization filed on or after 180 days after the date of the enactment of this Act. SEC. 4. AUTHORIZATION TO SERVE LEGAL PROCESS IN CHILD SUPPORT CASES ON CERTAIN ARRIVING ALIENS. (a) In General.--Section 235(d) of the Immigration and Nationality Act (8 U.S.C. 1225(d)), as amended by section 302 of the Illegal Immigration Reform and Immigrant Responsibility Act of 1996 (Public Law 104-208; 110 Stat. 3009-584), is amended by adding at the end the following: ``(5) Authority to serve process in child support cases.-- ``(A) In general.--To the extent consistent with State law, immigration officers are authorized to serve on any alien who is an applicant for admission to the United States legal process with respect to any action to enforce or establish a legal obligation of an individual to pay child support (as defined in section 459(i) of the Social Security Act). ``(B) Definition.--For purposes of subparagraph (A), the term `legal process' means any writ, order, summons or other similar process, which is issued by-- ``(i) a court or an administrative agency of competent jurisdiction in any State, territory, or possession of the United States; or (ii) an authorized official pursuant to an order of such a court or agency or pursuant to State or local law.''. (b) Effective Date.--The amendment made by this section shall apply to aliens applying for admission to the United States on or after 180 days after the date of the enactment of this Act. SEC. 5. AUTHORITY TO OBTAIN INFORMATION ON CHILD SUPPORT PAYMENTS BY ALIENS. Section 453(h) of the Social Security Act (42 U.S.C. 653(h)) is amended by adding at the end the following: ``(3) Provision to immigration and naturalization service of information on persons delinquent in child support payments.--On request by the Immigration and Naturalization Service, the Secretary shall provide the Immigration and Naturalization Service with such information in the Federal Case Registry of Child Support Orders as may aid in determining whether an alien is delinquent in the payment of child support.''.
Amends the Immigration and Nationality Act, as amended by the Illegal Immigration Reform and Immigrant Responsibility Act of 1996, to make certain aliens determined to be delinquent in child support payments inadmissable, deportable, and ineligible for naturalization. Authorizes immigration officers to serve child support-related legal process on certain arriving aliens. Amends the Social Security Act to provide for Immigration and Naturalization Service access to certain delinquent child support information.
radio pulsars are rotating , magnetized neutron stars ( nss ) emitting radio beams from magnetic poles . their masses are in the range of @xmath3 , radii @xmath4 km , densities @xmath5 and surface values of the dipolar magnetic field are around @xmath6 gauss . presently there are 1864 radio pulsars with their spin periods covering a wide range 1.39 ms @xmath7 11.78 s. this number is increasing quite rapidly after the first serendipitous discovery in 1967 by jocelyn bell , a graduate student in cambridge @xcite . pulsars are believed to be born with spin period @xmath8 s which increases very slowly with time ( at the rate of @xmath9 ) as their rotational energy is emitted in the form of electromagnetic energy . millisecond spin periods are explained as a result of spin - up process , which occurs when a neutron star has a normal star as its binary companion and accretes matter from the companion ( at its red giant phase ) causing transfer of angular momentum . depending upon the evolution of the companion , the resultant millisecond pulsar can be either isolated or a member of a binary system . in this article we concentrate on binary pulsars and discuss how the knowledge of their orbital parameters help us to understand the structure , formation , evolution and dynamic history of pulsars . as an example , binary millisecond pulsars are expected to be in circular orbits as tidal coupling during the accretion phase lead to orbit circularization . but if there is no history of accretion phase , the orbit of the binary pulsar can be eccentric because of the asymmetric kick imparted to the pulsar during its birth in a supernova . a millisecond pulsar binary can also have an eccentric orbit if it experiences interactions with other near - by stars ( which is possible in dense stellar environments like globular clusters ) or if it is a member of a hierarchical triple . it is noteworthy to mention here that in addition to radio wavelengths , pulsars emit in x - rays and/or gamma rays too . but radio pulsars are the most useful astronomical objects firstly because the underlying neutron stars are more stable than in the case of x - ray pulsars which have episodically varying accretion torques ; secondly high sensitivities of radio telescopes and data analysis software make it possible to determine their spin periods very accurately . moreover , for radio pulsars in binary systems ( @xmath10 of presently known radio pulsars are in binary systems ) , it is possible to determine the mass of the pulsar and its companion , size and shape of the orbit @xmath11 by modelling keplerian and post - keplerian parameters . such accurate determination of those parameters are difficult for x - ray pulsars at present . that is why we concentrate only on binary radio pulsars when we try to use the knowledge about their orbital parameters to understand the properties of pulsars . the first binary pulsar psr b1913 + 16 was discovered in 1974 at arecibo observatory by r. hulse and j. h. taylor @xcite which is a 59 ms pulsar having orbital period 0.323 days and orbital eccentricities 0.671 . interestingly , its @xmath12 mass companion star is most probably another neutron star @xmath0 the first discovered binary pulsar is also the first discovered double neutron star ( candidate ) system . afterwords nine other double neutron star ( dns ) systems have been discovered . among these ten dnss , seven systems are confirmed to be dnss and the rest are most likely to be dnss @xcite . these dnss are useful tools to test the validity of the general theory of relativity @xcite and even in principle to constrain the dense matter equations of state @xcite . in section [ sec : dns ] we discuss how the study of dnss can lead to a better understanding of the structure of neutron stars ( @xmath13 the equation of state ) , the physics of the pulsar magnetosphere and the formation scenario for the special case of the double pulsar system . most of the binary pulsars have either main sequence ( ms ) or white dwarf ( wd ) companions . knowledge about the values of the orbital parameters as well as of the spin periods and the masses of these pulsars ( and their companions ) might be useful to understand the evolutionary history of these systems . the possible causes of eccentricities of millisecond pulsar binaries have been studied in this article . when these systems are in dense stellar environments as in globular clusters , the eccentricities can arise as a result of different types of interactions of single stars with pulsar binaries like fly - by " , exchange " and merger " ( section [ sec : gc ] ) . the eccentricity of the only eccentric millisecond pulsar psr j@xmath14 in the galactic disk is difficult to explain as the hierarchical triple scenario faces difficulties to satisfy observed parameters of this system and the globular cluster origin also appears to be unlikely ( section [ sec : triple ] ) . all the findings of the present work have been summarized in section [ sec : summary ] . after performing pulsar observations , one determines time of arrivals " ( toas ) of pulses at the telescope . then various clock corrections are applied to the toas , followed by some other corrections @xmath15 rmer delay " , shapiro delay " and einstein delay " to calculate the toas with respect to the solar system barycenter . then the correction for the frequency dependent delay ( dispersion ) by the interstellar medium is added . finally , the pulse phase @xmath16 is fitted with time as a taylor series expansion like @xmath17 where @xmath18 and @xmath19 are reference phase and time , @xmath20 and @xmath21 are the spin frequency and its first time derivative . in case of a binary pulsar , one needs to model the orbital motion of the pulsar , and before doing that same type of delays for the binary system ( @xmath15 another set of rmer delay " , shapiro delay " and einstein delay " ) should be taken into account . for a non - relativistic binary pulsar , five keplerian parameters are required to describe the orbit , these are the orbital period ( @xmath22 ) , projected semi - major axis of the pulsar orbit ( @xmath23 , where @xmath24 is the inclination of the orbit with respect to the sky plane ) , orbital eccentricity ( @xmath25 ) , longitude of periastron ( @xmath26 ) and the epoch of the periastron passage ( @xmath27 ) . the semi major axes of the pulsar orbit and the companion orbit can be written as @xmath28 and @xmath29 respectively where @xmath30 is the semi major axis of the relative orbit coming in the kepler s law @xmath31 . here @xmath32 is the mass of the pulsar and @xmath33 is the mass of the companion . pulsar timing analysis means first getting an initial fit for the orbital parameters by inspecting the variation of the pulse period ( which is equal to the spin period @xmath34 of the pulsar ) and then improving the values of the parameters through a phase connected timing solution . but for relativistic binaries ( @xmath0 when the companion of the pulsar is another neutron star or a white dwarf ) , five post - keplerian ( pk ) parameters are needed , which are the relativistic advance of periastron ( @xmath35 ) , redshift parameter ( @xmath36 ) , shapiro parameters ( range @xmath37 " and shape @xmath38 " ) and the rate of change of orbital period ( @xmath39 ) due to gravitational wave emission . details of all the above mentioned parameters and how they are used in the timing models are described very nicely in handbook of pulsar astronomy " by d. r. lorimer and m. kramer @xcite . post - keplerian descriptions of the orbits are essential for double neutron star " ( dns ) binaries which include psr j0737 - 3039(a , b ) , psr b1534 + 12 , psr j1756 - 2251 , psr j1811 - 173 , psr j1906 + 0746 , psr b1913 + 16 , psr b2127 + 11c ( confirmed dnss ) , psr j1518 + 4904 , psr b1820 - 11 , psr j1829 + 2456 ( candidate dnss - orbital parameters hint dns nature but companion mass informations are insufficient to confirm ) . only one of the dnss , namely psr j0737 - 3039 is a double pulsar system @xmath0 both the neutron stars emit radio pulses . this feature has made this system a unique astrophysical laboratory and we shall discuss about it in more details in subsections [ subsec : eos ] , [ subsec : intab ] and [ subsec : form_double ] . moreover , there are three relativistic ns - wd systems - psr j0751 + 1807 , psr j1757 - 5322 , psr j1141 - 6545 for which also post - keplerian descriptions are unavoidable . let us now try to understand how dnss can help us in better understanding of the structure of neutron stars , physics of the pulsar magnetosphere and formation scenario ( for the special case of the double pulsar system ) of neutron stars . after the first proposal of neutron star as the ultimate fate of stars ( of mass @xmath40 ) by baade and zwicky in 1934 @xcite and the immediate prediction of mass and radius by oppenheimer and volkoff in 1939 @xcite , many people worked to understand the nature of matter at such high densities , resulting a large number of equations of states ( esos ) including the esos for strange quark matter . different esos result different mass - radius relations - see fig 2 of @xcite to realize how different the mass - radius curves can be . so the question arises , how to test the validity of those esos . presently there are a number of efforts to constrain the esos through astronomical observations in x - rays . the usual approach is to determine the mass and the radius of the stars with the help of various observational features like gravitational redshifts ( z ) from spectral lines , cooling characteristics , khz quasi - periodic oscillations ( qpo ) etc @xcite . but these methods are not foolproof , @xmath15 the value of z used in zel s @xcite analysis of exo 0748@xmath7676 could not be reproduced afterwords @xcite . moreover , to constrain esos from qpo observations , one needs to believe in a particular model of qpo which is again a subject of debate . an alternative method to constrain the dense matter esos might be the measurement of the moment of inertia of a neutron star in a relativistic binary , especially for a dns system and to match this observationally determined value with the theoretically predicted one . the equation of state ( eos ) which gives the best agreement between observed and the theoretical values of the moment of inertia of the ns can be considered as the best description of ns structure . the moment of inertia of a neutron star of known mass can be theoretically calculated for any particular eos either using hartle s approximations @xcite or by performing exact calculations @xcite for the rotating axisymmetric neutron star . it has been checked that the values of moment of inertia for a particular ns obtained by this two approaches do not differ more than 1% for a star like psr j0737 - 3039a @xcite . we found the moment of inertia of psr j0737 - 3039a to be in the range @xmath41 for a set of esos having different stiffness @xcite . let us now discuss about observational determination of the moment of a neutron star by accurate measurement of the periastron advance ( @xmath35 ) of the orbit of a relativistic binary pulsar ( preferably a dns ) through timing analysis . the theoretical expression of @xmath35 including the effect of spin - orbit coupling is known to be as follow @xcite : @xmath42 \label{eq : per_adv}\ ] ] where the first term inside the square bracket is the 1pn term , the second term is the 2pn term , and the third term represents the spin - orbit coupling ( so ) . the parameters used in the above expression are defined as : @xmath43 @xmath44 @xmath45 @xmath46 \\ \label{eq : gs}\end{aligned}\ ] ] where @xmath47 is the gravitational constant , @xmath48 is the moment of inertia of the @xmath49 body ( @xmath50 ) , @xmath51 is its angular velocity of rotation ( here @xmath52 means modulo 2 , @xmath0 2 + 1=1 ) and @xmath53 . @xmath54 is the spin period of the @xmath49 star and @xmath22 is the orbital period of the binary . @xmath55 and @xmath56 . @xmath57 is the orbital angular momentum vector , @xmath58 is the spin vector , @xmath59 is the line of sight vector perpendicular to the sky and @xmath24 is the inclination of the orbit with respect to the sky implying that the angle between @xmath59 and @xmath57 is also @xmath24 . in the expression of @xmath35 , the moment of inertia of both members of the dns system are present ( through @xmath60 and @xmath61 in eqn . [ eq : per_adv ] ) which means that we have only one observable and two unknowns making eqn . ( [ eq : per_adv ] ) unsolvable . but fortunately , @xmath62 is negligible for @xmath63 ms . so if @xmath64 ms , equation for periastron advance becomes @xmath65 \label{eq : per_advnew}\ ] ] so dns binaries having one fast neutron star ( @xmath66 ms ) and another slow neutron star ( @xmath67 ms ) are needed to extract the moment of inertia of the faster one by equating the observed @xmath35 with the prediction of eqn . ( [ eq : per_advnew ] ) using measured values of @xmath25 , @xmath22 , @xmath24 , @xmath68 , @xmath69 and @xmath70 . it is clear that the angle between @xmath71 and @xmath57 plays a vital to in the expression of @xmath72 . if @xmath73 , the angle between @xmath59 and @xmath71 becomes @xmath24 and we get @xmath74 . but if this is not the case @xmath0 the angle between @xmath71 and @xmath75 has a non - zero value , @xmath72 will be maximum if @xmath76 is parallel to the vector @xmath77 $ ] giving @xmath78^{1/2}\left[\frac{x_1 \left(4x_1 + 3x_{2 } \right)}{3 \left(1-e^2 \right)^{1/2}}\right]$ ] , for other orientation of @xmath71 , @xmath72 will be between @xmath79 to @xmath80 . so the knowledge of the angle between @xmath57 and @xmath76 is needed for determination of the moment of inertia of the faster member of a dns system . at present , it seems that the use of eqn . ( [ eq : per_advnew ] ) to determine the moment of inertia of a neutron star is possible only for the double pulsar system psr j0737 - 3039 @xcite , as for this system , timing analysis of the pulses from both the stars has already enabled us to determine @xmath25 , @xmath22 , @xmath68 , @xmath69 , @xmath70 and @xmath81 @xcite . the two pulsars which are named as psr j0737 - 3039a and psr j0737 - 3039b have masses and spin periods as @xmath82 , @xmath83 , @xmath84 ms and @xmath85 s with orbital parameters as @xmath86 , @xmath87 days , @xmath88 , @xmath89 . so it is clear that we can easily neglect the spin - orbit term due to pulsar b. although the angles between the vectors @xmath90 and @xmath91 are not known which are needed to be determined first to measure the moment of inertia of the pulsar a accurately . just for the sake of completeness , we wish to mention that for psr j0737 - 3039 , the value of @xmath92 is 1.2176 whereas the value of @xmath93 is 0.60876 . the accuracies of other relevant parameters are also needed to be improved . in general , it is clear that the @xmath94 term in eqn . ( [ eq : per_advnew ] ) will have higher value for ( i ) smaller value of @xmath95 , ( ii ) smaller value of @xmath22 and ( iii ) higher value of @xmath25 . unfortunately , the eccentricity of psr j0737 - 3039 is small in comparison to other dnss . future discovery of any double pulsar system satisfying these three conditions better than psr j0737 - 3039 will be useful for the purpose of moment of inertia measurement ( in addition to the necessary condition @xmath96 ms ) . among many interesting features observed from the double pulsar system psr j0737 - 3039 , one is the variation of the flux density of the slower pulsar b at its different orbital phases due to the distortion of b s magnetosphere by a s wind @xcite . on the other hand , the flux density of pulsar a is constant for most of its orbit except @xmath97 s near its superior conjuction when the radio beam from the pulsar a is eclipsed by the magnetosphere of the pulsar b @xcite . the eclipse is asymmetric , with the flux density decreasing more slowly during ingress than it increases during egress . the duration of the eclipse is very mildly dependent on the observing frequencies , with the eclipse lasting slightly longer at lower frequencies @xcite . theoretical models explain these eclipse properties in the context of synchrotron absorption of a s radio emission by the plasma in the closed field line region of b s magnetosphere @xcite . by modeling the eclipse , the precession of b s spin axis about the orbital momentum vector has been found to match with the prediction of the general theory of relativity within the @xmath98 measurement uncertainty @xcite . it is noteworthy to mention here that till date , the eclipse has been studied in the observing frequency range 427 - 1400 mhz . the study of psr j0737 - 3039 ( both a and b ) at a much lower frequency of 326 mhz is being performed using ooty radio telescope ( rac - tifr , ooty , india ) . the details of eclipse characteristic at this low frequency will be useful to test the validity of the eclipse models and better understanding of the pulsar magnetosphere . using observed parameters of the double pulsar system , different formation models were proposed @xcite . initially , it was proposed that this system has originated from a close helium star plus a neutron star binary in which at the onset of the evolution the helium star had a mass in the range 4.0 @xmath7 6.5 @xmath99 and an orbital period in the range 0.1 @xmath7 0.2 day @xcite . in this model , a kick velocity in the range 70 @xmath7 230 @xmath100 must have been imparted to the second neutron star at its birth . afterwords an electron capture supernova scenario was proposed @xcite . at the same time , piran & shaviv @xcite estimated that it is most likely that the progenitor of the pulsar b had a mass of @xmath101 with a low kick velocity 30 @xmath100 . on the other hand , a study based on the population synthesis method @xcite favored the standard formation scenario with reasonably high kick velocities ( 70 - 180 @xmath100 ) . later , it has been suggested @xcite that the pulsar b is a strange star rather than a neutron star as the baryon loss is smaller for the first case supporting the models with small kick . globular clusters ( gcs ) are dense spherical collection of stars orbiting around the galactic center containing a significant number of binary stars . the first radio pulsar discovered in a globular cluster is psr b1821 - 24a in m28 @xcite in 1987 , 20 years after the discovery of first pulsar by jocelyn bell . this pulsar is at present an isolated pulsar but its very low spin period ( 3 millisecond ) hints to a binary origin and spin - up due to accretion . how old and evolved stellar systems like gcs can contain apparently young , active objects like pulsars have led to suggestions , based on lifetime constraints from orbital decay by gravitational radiation @xcite , that some of these systems have been formed recently , or are forming even today . interaction between binary stars and single stars in gcs is believed to be an important dynamical process as the resulting binary systems may provide a substantial source of energy for the host gc , as the binding energies of a few , very close binaries ( like neutron star binaries ) can approach that of a moderately massive gc @xcite . observable parameters of the pulsars and their binary companions in gcs , such as spin , orbital period and eccentricity , projected radial position in the cluster , companion mass and their distributions provide a tracer of the past history of dynamical interactions of the binary nss in individual gcs . these parameters can even provide a valuable test - bed to examine the theoretical scenarios of formation and evolution of recycled pulsars . till today , a total of 140 pulsars in 26 gcspfreire / gcpsr.html . ] have been discovered . among them 74 are known as binaries ( in 23 gcs ) , 59 are known as isolated and 7 have no published timing / orbital solutions . orbital parameters of one binary , namely psr j2140@xmath72310b in m30 are not well determined , only lower limits of @xmath22 and @xmath25 are known as @xmath102 days and @xmath103 . so we exclude it from our analysis and proceed with the rest 73 binaries . in fig [ fig : porbecc_gc ] , we plot @xmath25 vs @xmath22 for these 73 binary pulsars in gcs with known orbital solutions . a logarithmic scale in both eccentricity and orbital periods are chosen , as the enormous range of both variables and the regions occupied by observed pulsars are less obvious in linear scales . downward arrows have been drawn for the systems for which only upper limits of eccentricities ( see table [ tab : gcpsr_parms ] ) are known . non - millisecond pulsars are enclosed by @xmath104s and the dns system psr b2127@xmath10511c in m15 is enclosed by a green @xmath106 . in the present work , we define millisecond pulsars as the pulsars having @xmath107 ms , we do nt go for other definitions of millisecond pulsars based on both @xmath34 and @xmath108 ( see @xcite for one such definition ) as for gc binaries , the values of @xmath108 are effected significantly by the cluster potential . observed binaries in gcs can be categorized in three groups : ( i ) large eccentricity pulsars ( @xmath109 ) , 21 pulsars ( 22 if we include m30b ) , ( ii ) moderate eccentricity pulsars ( @xmath110 ) , 20 pulsars and ( iii ) small eccentricity pulsars ( @xmath111 ) , 32 pulsars . in the database , orbital eccentricities of group ( iii ) pulsars have been listed as zero , and in this logarithmic plot we assign them an arbitrarily small value of @xmath112 . in addition we plot on the right of fig [ fig : porbecc_gc ] , dashed lines corresponding to the freeze - out eccentricity - orbital period relation predicted by phinney @xcite on the basis of the fluctuation dissipation theorem for convective eddies in the erstwhile red giant envelopes surrounding the white - dwarf cores which end up as companions of the neutron stars . this relation is obtained from the following expression : @xmath113 where @xmath114 is the orbital angular rotation frequency , @xmath30 is the semi - major axis of the binary , @xmath25 is the orbital eccentricity , l is the luminosity of the companion , @xmath115 is the radius of the companion , @xmath116 is the envelop mass of the companion , @xmath32 is the pulsar mass , @xmath33 is the companion mass and @xmath117 is the reduced mass of the system . phinney used @xmath118 when the mass transfer ceases and @xmath25 freezes . then the above equation reduces to @xmath119 where @xmath120 is a function of the effective temperature ( @xmath121 ) , @xmath122 and @xmath116 . @xmath22 is in days . phinney calculated @xmath123 ( see eqn . 7.35 of @xcite ) using average values of @xmath116 and @xmath121 for population i stars ( @xmath124 ) @xcite which gives the upper dashed green line in the right side of fig [ fig : porbecc_gc ] . however for globular clusters , population ii stars are more appropriate . so we recalculated @xmath120 for population ii red giant stars @xcite and obtained @xmath125 . this line is plotted as the lower dashed green line in fig . [ fig : porbecc_gc ] . earlier , it had been found that while the low mass x - ray binaries ( lmxbs ) are predominantly found in very dense gcs , the radio pulsars tend to be found more evenly distributed among low and high density clusters @xcite . we also do nt find any obvious correlation of the number of binary radio pulsars with any gc parameters like @xmath126 , @xmath127 , @xmath128 or @xmath129 ( where @xmath128 is the number density ( @xmath130 ) of single stars in units of @xmath131 and @xmath127 is the velocity dispersion ( @xmath132 ) in units of 10 @xmath133 in gcs and @xmath126 is the distance of the gcs from sun in kpc see table [ tb : gc_v_n ] ) . but if we take only gcs with more than 3 observed binary pulsars , we find the number of binary pulsars to increase with @xmath128 , but there are only five such gcs ( table [ tb : gc_v_n ] ) . there are total 83 binary pulsars in the galactic disk ( and 1652 isolated pulsars ) among which orbital period and/or eccentricity values are unknown for four binaries . so we exclude them from our study and we consider the rest 78 binary pulsars . in the database , eccentricities of three binaries have assigned the value 0 " for which we put an arbitrary small value @xmath134 ( as in the case of gc binary pulsars ) . in fig [ fig : porbecc_gc_gal ] , we plot @xmath25 vs @xmath22 for all binary pulsars with known orbital solutions . blue @xmath135s are for gc binaries and red @xmath136s are for disk binaries . three disk binaries with @xmath137 days have not been plotted here as we have selected the range of @xmath22 up to 1000 days in this plot . here we take upper values of eccentricities as the actual values . dnss are enclosed by green @xmath106s . non - millisecond pulsars are enclosed by @xmath104s . it is believed that millisecond pulsars in binary systems formed from mass and angular momentum transfer due to roche lobe overflow and the resultant tidal effects should appear in @xmath138 @xcite . since many highly eccentric binary millisecond pulsars are found in gcs , this indicates that stellar interactions are important for inducing higher eccentricities which will be discussed later in this section . on the other hand , psr j@xmath14 is the only one eccentric millisecond pulsar in the disk and there are lots of works in the recent past to explain the eccentricity of this system @xcite . we shall discuss about this system in somewhat details in section [ sec : triple ] . observational selection effects may be influencing the distribution seen in this figure for the two sets @xcite , the most important selection effect being operative towards the left of the diagram , namely , it is more difficult to detect millisecond pulsars in very short orbital period and highly eccentric binaries ; distance to the pulsars also is an important selection effect , since at large distance only the brightest pulsars can be observed . nevertheless , it is clear that there is a large abundance of pulsars with long orbital periods and intermediate eccentricity near the eddy fluctuation dissipation " lines among the galactic disk pulsars which are absent in the gc pulsar population , where the important selection effects are unlikely to play a major role . the observed preponderance of dnss in the disk with the very short orbital periods and large eccentricities may be related to selection effects , but there is at least one dns in gc - psr j2127 + 1105c in m15 in the same phase - space . the disk dnss are by and large at small distances while m15 and other host gcs are usually far away . in the top panel of fig . [ fig : mc_ps_hist ] we compare the distribution of @xmath33s for the gc and the disk binaries and found that there are more low mass companions for gc binaries . in the bottom panel of fig . [ fig : mc_ps_hist ] we compare the distribution of @xmath34s for the gc and the disk binaries and found that in gcs , most are millisecond pulsars while for disk pulsars , @xmath34 are more uniformly distributed ( not completely , more pulsars with lower @xmath34 ) over a wide range . in the left panel of fig . [ fig:3dplots ] , we plot @xmath22 , @xmath25 and @xmath33 for all binaries while in the right panel we plot @xmath22 , @xmath25 and @xmath34 . in both cases , blue points represent gc binaries and red points represent disk binaries . three disk binaries with @xmath139(see table [ tab : diskpsr_parms ] ) have been omitted from the plot in the left panel , even then we can see that companion masses of disk binaries are usually higher than those of gc binaries . nearly circular binary pulsars have low mass companions . it was proposed that orbital parameters of binary pulsars with white - dwarf companions satisfy the following relation @xcite : @xmath140^{3/2}\,m^{-1/2}_{c } \label{eq : rappaport}\ ] ] in the upper panel of fig . [ fig : rappaport ] , we plot @xmath141 against @xmath33 for binary pulsars in gcs and also in the galactic disk . dns binaries and the binaries with @xmath142 ( chandrasekhar limit ) have been excluded . gc binaries are shown with blue @xmath135s and disk binaries are shown with red @xmath136s . the points correspond to median values of @xmath33 taking @xmath143 while the upper and the lower limits of @xmath33s correspond to @xmath144 and @xmath145 respectively . theoretical prediction following eqn . ( [ eq : rappaport ] ) is the middle solid green line . the upper and lower lines are obtained by multiplying the right hand side of eqn . ( [ fig : rappaport ] ) by 2.5 ( see @xcite ) . note that the model used to derive eqn . ( [ eq : rappaport ] ) is not valid when @xmath146 , though we have plotted the binaries with @xmath147 ( located left of the vertical black dotted line ) just to see how @xmath141 is related with @xmath33 for these systems . for recycled ( millisecond ) pulsars , where significant amount of mass had been transferred to the pulsars in past , one should expect lower values of @xmath33 and @xmath138 . for these cases the relation becomes @xmath148^{3/2}\,m^{-1/2}_{c } \label{eq : rappaport_zero}\ ] ] the deviation of gc binary pulsars from the theoretical prediction of eqn . ( [ eq : rappaport ] ) is well understood as their eccentricities have been effected by stellar interactions . so for the millisecond pulsar binaries in gcs ( which naturally exclude the dns in m15 ) , we plot eqn . ( [ eq : rappaport_zero ] ) in the lower panel of fig . ( [ fig : rappaport ] ) . even then we found significant discrepancy between the theoretical prediction and the observed values . moreover , for binary pulsars in the disk ( upper panel of fig . [ fig : rappaport ] ) where eccentricities and orbital periods should bear the clear signature of stellar evolutions , we also found disagreement between the model and the observation . we summarize the relevant properties of the host gcs and in table ( [ tb : gc_v_n ] ) . the properties of binary pulsars in globular clusters and in the galactic disk are given in tables ( [ tab : gcpsr_parms ] ) and ( [ tab : diskpsr_parms ] ) respectively . interested readers are requested to see original sources for better precision of the given parameters and for the values of other parameters . through a combination of two - body tidal captures and exchange interactions where an isolated neutron star replaces a normal star in a binary , numerous neutron star binaries are formed in gcs @xcite . this explains why the ratio of binary pulsars to isolated pulsars is so high in gcs in comparison to that in the galactic disk . tidal capture leads to tight binaries whereas exchange usually leads to wider binaries ( see eqns . [ eq : afin_ex ] ) . if the mass transfer in the tidally captured neutron star binary happen in a stable manner , it can spin up the neutron star to a millisecond spin period . thus the observed preponderance of millisecond pulsars in gc binaries can be attributed to the tidal capture process ( details will be discussed in the next subsection ) . we explain the eccentricities of millisecond pulsar binaries in gcs as a result of different types of interactions of single stars with pulsar binaries using present properties of the gcs . some of the results can be found in our earlier papers @xcite . for the sake of simplicity , we do nt go for a full population synthesis study of the evolution of the globular clusters including all kinds of stellar interactions @xmath15 binary - binary , binary - single star and single star - single star interactions . we consider only binary - single star interactions faced by binary pulsars preceded by a discussion on the formation of binary pulsars through tidal capture . globular clusters contain a large number of lmxbs compared to the galactic disk ; this had led to the suggestion @xcite that a binary is formed by the tidal capture of a non - compact star by a neutron star in the dense stellar environment of the gc cores . if mass and angular momentum transfer from the companion to the neutron star took place in a stable manner , this could lead to recycled pulsars in binaries or as single millisecond pulsars @xcite . however large energies may be deposited in tides after the tidal capture of a neutron star by a low mass ms star in a gc . the resultant structural readjustments of the star in response to the dissipation of the modes could be very significant in stars with either convective or radiative damping zones @xcite and the companion star can undergo a size inflation " due to its high tidal luminosity which may exceed that induced by nuclear reactions in the core , by a large factor . efficiency of viscous dissipation and orbit evolution is crucial to the subsequent evolution of the system as viscosity regulates the growth of oscillations and the degree to which the extended star is bloated and shed . the evolution of the system could lead to either a merger ( leading to a thorne zytkow object ) or a neutron star surrounded by a massive disk comprising of the stellar debris of its erstwhile companion or , in other cases , an lmxb or even a detached binary following envelope ejection . tidal oscillation energy can return to the orbit ( i.e. the tide orbit coupling is a dynamical effect ) thus affecting the orbit evolution or the extent of dissipative heating in the less dense companion . the evolutionary transition from initial tidal dynamics to any likely final , quiescent binary system is thus regulated by viscosity . tide orbit coupling can even lead to chaotic evolution of the orbit in some cases @xcite but in the presence of dissipation with non - liner damping , the chaotic phase may last only for about 200 yrs after which the binary may undergo a periodic circularization and after about 5 myrs finish circularizing @xcite . of the stars that do not directly lead to mergers , a roughly equal fraction of the encounters lead to binaries that either become unbound as a result of de - excitation or heating from other stars in the vicinity or they are scattered into orbits with large pericenters ( compared to the size of the non - compact star ) due to angular momentum transfer from other stars @xcite . thus intermediate pericenter " encounters can lead to widened orbit ( even 100 days orbital period in an eccentric orbit ) in tidal encounters involving main sequence stars and neutron stars , which in the standard scenario are attributed to encounters between giants and neutron stars . the complexities of the dynamics of tidal capture and subsequent evolution are manifold and attempts to numerically simulate collisions of neutron stars with red giants have been made with 3d smoothed particle hydrodynamics ( sph ) codes @xcite . we note in this context that podsiadlowski @xmath149 @xcite have stated it is not only premature to rule out tidal capture as a formation scenario for lmxbs , but that lmxbs in globular clusters with well determined orbital periods actually provide observational evidence in its favor " . the different formation channels of pulsars in binaries in gcs and the birthrate problems of millisecond pulsar binaries vs lmxbs were considered in @xcite . until the early eighties there was no evidence of a substantial population of primordial binaries in any globular clusters , and it was even thought that gcs are significantly deficient in binaries compared to a younger galactic population @xcite . theoretical modeling of gcs was often started off as if all stars were singles . during the 1980s several observational techniques began to yield a rich population of binary stars in gcs @xcite . when the local binary fraction is substantial , the single star - binary interaction can exceed the encounter rate between single stars by a large factor @xcite . the existence of a significant population of primordial binary population in gcs indicated that three body processes have to be accounted for in any dynamical study of binaries involving compact stars . an encounter between an isolated star and a binary may lead to a change of state of the latter , e.g. : i ) the original binary may undergo a change of eccentricity and orbital period but otherwise remain intact a preservation " or a fly - by " process ; ii ) a member of the binary may be exchanged with the incoming field star , forming a new binary an exchange " process ; iii ) two of the stars may collide and merge into a single object , and may or may not remain bound to the third star - a merger " process ; iv ) three of the stars may collide and merge into a single object - a triple merger " process ; v ) all three stars may become unbound - an ionization " process . the ionization is always a prompt " process , whereas the others can be either prompt or resonant " process . in resonant processes , the stars form a temporarily bound triple system , with a negative total energy but which decays into an escaping star and a binary , typically after 10 - 100 crossing times . the value of the binding energy of the binary and the velocity of the incoming star determine the type of interaction the binary will encounter . the critical velocity @xmath150 of the incoming star , for which the total energy ( kinetic plus potential ) of the three body system is zero , can be defined as @xmath151 where @xmath68 and @xmath69 are the masses of the binary members , @xmath152 is the mass of the incoming star , @xmath153 is the semi - major axis of the binary and g is the gravitational constant . in case of a binary - single star interaction , semi major axis of the final binary ( @xmath154 ) is related to the semi major axis of the initial binary ( @xmath153 ) as follows @xcite : @xmath155 where @xmath68 and @xmath69 are masses of the members of the initial binary , @xmath156 and @xmath157 are masses of the members of the final binary . @xmath158 is the fractional change of binary binding energy @xmath0 @xmath159 . the binding energies of the initial and final binaries are @xmath160 for fly - by , @xmath161 , @xmath162 giving @xmath163 for exchange , @xmath161 , @xmath164 ( star 2 is being replaced by star 3 ) giving @xmath165 for merger , @xmath161 , @xmath166 ( star 2 is being merged with star 3 ) giving @xmath167 the actual value of @xmath158 is not known . putting @xmath168 simplifies equations ( [ eq : afin_gen ] ) , ( [ eq : afin_fly ] ) , ( [ eq : afin_ex ] ) and ( [ eq : afin_merg ] ) giving @xmath169 for fly - by interactions . similar expressions can be derived for other cases @xmath15 star 1 is being replaced by star 3 or star 1 being merged with star 3 . but in the present study , we always assume star 1 to be the neutron star , so these processes are irrelevant . merger interactions which do not result in binary systems are also irrelevant for this work . interactions between binaries and single stars can enhance the eccentricity of the binary orbit and this will be discussed in detail in the subsequent sections . on the other hand , binary pulsars emit gravitational waves which reduce both the sizes and eccentricities of the orbit leading to mergers of the binary members on a timescale of @xmath170 which can be calculated as follows @xcite : @xmath171 where @xmath172 and @xmath173 which is almost same as the expression of @xmath170 calculated from @xmath174 . @xmath175 @xmath176 and @xmath177 in this work , we use eq . ( [ eq : tgr_e ] ) to calculate @xmath170 . figs . [ fig : porbecc_gc ] , [ fig : porbecc_gc_gal ] and table [ tab : gcpsr_parms ] show that most of the binary pulsars in gcs are millisecond pulsars ( 69 pulsars out of 73 have @xmath178 ms , one has @xmath179 ms and the other three having @xmath34 values as 80.34 ms , 111.61 ms and 1 s ) . theoretically one expects that spun - up , millisecond pulsars in binary systems formed from mass and angular momentum transfer due to roche lobe overflow and the resultant tidal effects should appear in low eccentricity orbits @xmath180 @xcite . since many highly eccentric binary millisecond pulsars are found in globular clusters ( see the right panel of fig [ fig:3dplots ] ) , this indicates that stellar interactions are important in gcs for inducing higher eccentricities . rasio and heggie @xcite studied the change of orbital eccentricity ( @xmath181 where @xmath182 is the initial eccentricity and @xmath183 is the final eccentricity which is observable at present ) of an initially circular binary ( @xmath184 ) following a distant encounter with a third star in a parabolic orbit . they used secular perturbation theory , i.e. averaging over the orbital motion of the binary for sufficiently large values of the pericenter distance @xmath185 where the encounter is quasi - adiabatic and used non secular perturbation theory for smaller values of @xmath185 where the encounter is non - adiabatic . in the first case @xmath186 varies as a power law with @xmath187 and in the second case @xmath186 varies exponentially with @xmath187 . the power law dominates for @xmath188 wheras the exponential law dominates for @xmath189 . the timescales for these processes are @xcite ( where we write @xmath25 in place of @xmath183 for the sake of simplicity ) : @xmath190^{-2/3 } ~\rm { ( e \gtrsim 0.01 ) } \label{eq : tfly2}\end{aligned}\ ] ] where @xmath22 is in days and @xmath191 is in years . the values of @xmath192 are different for different gcs ( table [ tb : gc_v_n ] ) and we grouped them into six different groups according to their values of @xmath192 and calculated @xmath191 for mean values of @xmath192 for each group . the unit of @xmath192 is @xmath193 which we will not mention explicitly anymore . cluster binary pulsars in the @xmath194 plane with contours of @xmath195 yrs ( solid lines ) and @xmath196 yrs ( dashed lines ) for each group are shown in fig [ fig : psr_all_group_rasio_fly ] . contours of @xmath197 yrs ( solid lines ) and @xmath198 yrs ( dashed lines ) for binaries with @xmath199 and @xmath200 or @xmath201 are also shown . pulsars with projected positions inside the cluster cores are marked with @xmath105 , those outside the cluster cores are marked with @xmath202 and the pulsars with unknown position offsets are marked with @xmath203 . solid red line corresponding to @xmath195 years for @xmath204 is outside the range of axes used in our plots ( away from the upper left corner ) . pulsars in a particular group are marked with the same color as of the @xmath191 contours for that group . the upper limits of eccentricities are taken as the actual values of eccentricities . if a pulsar is located on the upper left half of the corresponding @xmath195 years line @xmath0 in the region where @xmath205 years , then its eccentricity can not be due to fly - by interactions . there are two such binaries , one is psr b1718 - 19 ( in ngc 6342 , in group 4 ) and the other is psr b 1639 + 36b ( in m13 , in group 6 ) . but the first one is a normal pulsar with @xmath206 s and as it is not spun up and may not have been subject to a great deal of tidal forces , it can have escaped circularization . on the other hand , the second pulsar is a millisecond pulsar with @xmath207 ms , so it should have been in a circular orbit if it has not had the time to go through any significant kind of stellar interactions . therefore it is of interest to investigate if it is a result of an exchange or merger interaction . moreover , some of the eccentric pulsars which seem to be explainable by fly - by interactions lie outside of globular cluster cores ( where the stellar density is comparatively low and hence fly - by interactions are less efficient ) . for a few others positional offsets are not known . even if a pulsar appears to be inside the cluster core in the projected image , it can still be outside the cluster core in the three dimensional space . gc models show that values of both @xmath127 and @xmath128 fall outwards from the cluster center and as the fall of @xmath128 is much more rapid , the value of @xmath129 is higher outside the cluster core . as we have already seen ( different panels in fig . [ fig : psr_all_group_rasio_fly ] ) that an increase in the value of @xmath129 shifts the contour of @xmath208 years rightwards , this will make the pulsar fall in the region where @xmath209 years excluding the possibility of fly - by interaction as the cause of its eccentricity . in those cases also , we need to think about exchange and/or merger interactions . we have seen that there are many zero eccentricity pulsars which lie in the region where @xmath210 years . so it is of interest to understand why they still appear in circular orbits despite the possibility of fly - by interactions . we will discuss about this point in subsection [ sec : zero ] . since exchange and merger interactions have not been amenable to analytic treatment one needs to use numerical techniques . we performed numerical scattering experiments using the starlabstarlab/ ] task sigma3 " which gives the scaled cross section @xmath211 for different types of interactions , @xmath15 fly - by , exchange , merger and ionization ( both resonant and non - resonant ) . the inputs given are : velocity ( @xmath132 ) of the incoming star ( with mass and radius @xmath212 ) and the masses , the radii , the semi major axis of the initial binary ( @xmath213 ) as well as the trial density which determines the number of scattering experiments to be done . @xmath211 is defined as : @xmath214 where @xmath215 is the cross section and @xmath150 is the critical velocity as defined earlier ( eq . [ eq : vc ] ) . so from the reported values of @xmath211 , one can calculate @xmath215 and then the interaction time scale @xmath216 as @xmath217 where @xmath130 is the number density of single stars . we took different sets of stellar parameters ( @xmath218 ) to understand the effect of each of them and for each set of stellar parameters , we varied @xmath153 over a wide range in such a way that the initial orbital periods ( @xmath219 , calculated using kepler s law ) are in the range of @xmath220 days . for each set of parameters ( @xmath213 ) , we take the maximum trial density ( @xmath221 ) as 5000 which is uniformly distributed in the impact parameter ( @xmath222 ) over the range @xmath223 where @xmath224 simply corresponds to a periastron separation of @xmath225 . the impact parameter range is then systematically expanded to cover successive annuli of outer radii @xmath226 with @xmath221 trials each until no interesting interaction takes place in the outermost zone @xcite . thus the total number of trials become significantly large . as an example , for the parameters @xmath227 we had a sample total of 15570 scatterings . out of these 10960 were fly - bys , 3722 exchanges , 982 two mergers and 6 three - mergers . we performed simulations over widely different values of @xmath132 @xmath15 11.76 @xmath133 , 13.15 @xmath133 , 7.79 @xmath133 and 3.29 @xmath133 chosen in such a way that almost the entire range of @xmath192 ( @xmath228 respectively ) has been covered . the variation in @xmath132 is also significant . but we mainly concentrate on the runs for @xmath229 @xmath133 as in ter 5 , the host of the largest number of known binary radio pulsars . in fig . ( [ fig : x_porb ] ) we plot the variation of @xmath211 for exchange ( @xmath105 ) , merger ( @xmath136 ) and ionization ( @xmath230 , whenever significant ) with @xmath219 and check the dependencies on different parameters - ( i ) in the first figure , we set @xmath231 , @xmath232 , and take two values of @xmath132 @xmath15 13.16 @xmath133 ( red ) and 3.27 @xmath133 ( green ) which are the highest and the lowest values of @xmath132 among our choice ( see table [ tb : gc_v_n ] ) . ( ii ) in the second figure , we set @xmath233 @xmath234 , and take different values of @xmath69 @xmath15 @xmath235 ( red ) , @xmath236 ( green ) and @xmath237 ( blue ) . ionization starts for @xmath238 at @xmath239 days . ( iii ) in the third figure , we set @xmath240 @xmath241 @xmath133 , and take different values of @xmath152 @xmath15 @xmath242 ( red ) , @xmath243 ( green ) . ( iv ) in the fourth figure , we set @xmath244 , @xmath245 and take the @xmath246 star to be either an ms ( red ) or a wd ( green ) . the results can be summarized in a tabular form : 0.5 cm [ cols="^,^",options="header " , ] in the previous section , we have discussed how stellar interactions in globular clusters lead to binary millisecond pulsars in eccentric orbits . in the absence of such stellar interactions @xmath0 in the galactic disk , millisecond pulsars are expected to be in circular orbits as during the accretion phase ( recycling process ) , tidal coupling leads to orbit circularization . on the other hand , if the millisecond pulsar is the part of a hierarchical triple , consisting of inner and outer binaries , then as a result of kozai oscillation , the eccentricity of the inner binary can be large . to understand this mechanism , let us assume that a star of mass @xmath247 forms the inner binary with its companion of mass @xmath68 . another star of mass @xmath69 forms an outer binary with the center of mass of the inner binary . one can consider the inner and outer binaries to be isolated binaries of masses @xmath247 , @xmath68 and @xmath248 , @xmath69 respectively . let us denote the eccentricities , semi - major axes , inclinations with respect to the sky plane and the arguments of the periastrons ( with respect to their lines of nodes ) of the inner and outer binaries by @xmath249 and @xmath250 , respectively and the mutual inclination angle between the two orbits @xmath251 . then the magnitudes of the angular momenta @xmath252 and @xmath253 of the inner and outer binaries will be as follow : [ g12_eq ] @xmath254 where g is the gravitational constant , @xmath255 is the total mass of the inner binary and @xmath256 is the symmetric mass ratio of the inner binary , given by @xmath257 . the temporal evolution of the inner binary can be probed with the help of secular perturbation theory , applicable to newtonian hierarchical triples containing point masses , while including the dominant quadrupolar order interactions between the two orbits . in other words , the dynamical equations invoked are accurate to order @xmath258 , where @xmath259 is the small parameter in the perturbative expansion . the relevant equations providing secular temporal evolution for the eccentricity and the argument of periastron of the inner binary including the dominant order general relativistic effect that causes the periastron of an isolated compact binary to advance are @xcite : [ etgt_eq ] @xmath260^{3/2 } \,,\\ \label{dedtht } \dot{e}_1 & = \frac { 30\ , c_2 } { { \cal g}_1 } \ , { e_1(1-e_1 ^ 2)}\ , ( 1-\theta^2)\ , \sin 2 \omega_1 \,,\end{aligned}\ ] ] where @xmath261 . the quantity @xmath262 is @xmath263 note that the newtonian contributions to eqns . ( [ etgt_eq ] ) originate from certain ` doubly averaged ' hamiltonian , which is derivable from the usual hamiltonian for a hierarchical triple at the quadrupolar interaction order @xcite . the ` doubly averaged ' hamiltonian , suitable for describing secular ( long - term ) temporal evolution of a hierarchical triple , is independent of the mean anomalies of the inner and outer orbits . this implies that their respective conjugate momenta and hence the semi - major axes , @xmath264 and @xmath265 , are constants of motion . here changes in @xmath264 and @xmath266 due to gravitational wave radiation have been neglected . first two terms in eqn . ( [ dgdt ] ) give the rate of change of periastron due to the hierarchical triple configuration ( @xmath267 ) . the third term gives the rate of change of periastron due to the general relativistic effect ( @xmath268 ) up to 1pn order only and neglecting the spin - orbit coupling ( see eqn . [ eq : per_adv ] ) . it turns out that if the mutual inclination angle is fairly high and in a certain window , the orbital eccentricities experience periodic oscillations over time - scales that are extremely large compared to the respective orbital periods . the above effect , usually referred to as the kozai resonance , arises due to the tidal torquing between the two orbits @xcite . the kozai resonance can force initially tiny eccentricity of the inner binary to oscillate through a maximum value , given by @xmath269 where @xmath270 is the initial value for the mutual inclination angle . due to the obvious restriction , namely @xmath271 , @xmath270 is required to lie in the range @xmath272 . an approximate expression for the period of the kozai oscillation reads @xcite : @xmath273 where @xmath274 is the orbital period of the inner binary . the general relativistic periastron advance of the inner binary , in principle , can interfere with the kozai resonance and even terminate the eccentricity oscillations . this is because the extra contribution @xmath268 to @xmath275 can indirectly affect the evolution of @xmath266 . the following useful criterion can be used to infer the possibility for this not to happen @xcite : @xmath276^{1/3 } \,,\ ] ] where @xmath277 is @xmath278 and @xmath279 km . another constraint for @xmath280 can be obtained by invoking an empirical relation needed for the newtonian coplanar prograde orbits in hierarchical triple configurations @xcite : @xmath281 ^{2/5 } \,.\ ] ] we treat the above inequality to be rather conservative @xcite as the inclined orbits , relevant for our investigation , are expected to more stable than the coplanar triples of eq . ( [ alpha_ma ] ) . recently a millisecond pulsar ( @xmath282 ms ) psr j@xmath14 in a highly eccentric orbit around a solar mass companion in the galactic plane has been discovered @xcite . the discoverers almost discarded the born - fast " scenario for this pulsar and strongly favored a binary origin for it . so they had to explore unconventional formation scenarios . they favored the idea that this pulsar is a member of the inner binary of a triple system and kozai resonance is responsible for its high eccentricity . they have also speculated a globular cluster origin for the system , involving the ejection of the system from a globular cluster or the disruption of the cluster itself . accurate radio timing analysis of the pulsar ( using ` ddgr ' timing model @xcite ) reveals that the binary has the following properties - the orbital period is @xmath283 days , eccentricity is @xmath284 , pulsar mass is @xmath285 , companion mass is @xmath286 , the longitude of periastron is @xmath287 , the advance of periastron is @xmath288 @xcite . here the numbers in the parenthesis are twice the 1-@xmath215 uncertainties in the least significant digit(s ) . the companion mass was determined using the advance of periastron and the shapiro shape ( @xmath38 " ) parameter , assuming the advance of periastron to be only due to the general relativistic effect @xmath0 the third term in eqn . ( [ dgdt ] ) . infrared observations with gemini north telescope yielded a possible main - sequence companion star for the pulsar . the hierarchical triplet hypothesis for this system is that the pulsar and the companion ( either a neutron star or white dwarf as the pulsar is recycled - implying past accretion from the red - giant phase of its companion ) forms the inner binary and the main - sequence star is in a much wider orbit forming the outer binary . this means that the white - dwarf in the inner binary contributes in the timing analysis and the main - sequence star in the outer binary has been observed in infrared observation . so , in eqns . ( [ g12_eq ] ) , ( [ dgdt ] ) , ( [ dedtht ] ) , ( [ c2_def ] ) , ( [ t_kozai ] ) , ( [ alpha_gr ] ) and ( [ alpha_ma ] ) one can use @xmath289 , @xmath290 , @xmath291 , @xmath292 , @xmath293 . @xmath264 can be calculated from the orbital period ( @xmath294 days ) using kepler s law . but the problem here is the companion mass was found to be @xmath295 with an assumption that @xmath275 is only due to general relativistic effect ( third term in eqn . [ dgdt ] , @xmath268 ) on the other hand , for a hierarchical triple system all the terms in eqn . ( [ dgdt ] ) would contribute . so if this system is the part of a hierarchical triple , the value of the companion mass of the inner binary is likely to be different from the above mentioned value . so the timing - analysis of this system was continued . the latest value of the companion mass measured using only the shapiro shape ( @xmath38 " ) and range parameter ( @xmath37 " ) is @xmath296 . this matches with the earlier estimate using @xmath38 and @xmath297 supporting the assumption that the @xmath275 is purely relativistic @xcite . however , because of the lower precision in the measurement of @xmath37 , it is impossible to exclude small contributions to @xmath275 at present . using eqn . [ dgdt ] , we found that for preferable combination of @xmath298 the contribution form the first two terms in eqn . [ dgdt ] can be negligible in comparison to the third term . as an example , in fig . [ fig : gdot_htgr ] we plot the variation of @xmath267 and @xmath268 with @xmath69 and @xmath299 for a fixed @xmath300 ( for such combinations of @xmath69 , @xmath299 and @xmath301 that both the inequalities ( [ alpha_gr ] ) and ( [ alpha_ma ] ) are satisfied ) ; red points are for @xmath267 and green points are for @xmath268 . @xmath268 is independent of @xmath69 and @xmath299 ( see the third term of eqn . [ dgdt ] ) and matches with the observed value @xcite . we find that @xmath267 can be significantly less than @xmath268 for sufficiently small values of @xmath299 . in that case the companion mass measured using @xmath38 and @xmath37 can match with the measurement done with @xmath38 and @xmath297 assuming @xmath302 . but the precision of @xmath37 is still improving significantly with continued timing and it might be possible in future to confirm whether there is even any small deviation of @xmath297 from @xmath268 . in principle , @xmath303 measurement can also help to test the validity of hierarchical triple scenario . for a hierarchical triple system , the observed @xmath303 can be the combined effect of three terms like @xmath304 , where @xmath305 is the rate of change of eccentricity because of kozai oscillation in a hierarchical triple system given by eqn . ( [ dedtht ] ) , @xmath306 is the rate of change of eccentricity because of gravitational wave radiation given by eqn . ( [ eq : dedtgr ] ) and @xmath307 is due to geodetic precession of the pulsar spin axis ( see eqns . 8.58 , 8.82 and 8.91 of @xcite ) . it is clear from eqn . ( [ eq : dedtgr ] ) that @xmath306 is always negative and we found it to be @xmath308 for the inner binary as mentioned above . eqn . ( [ dedtht ] ) shows that @xmath305 can be positive or negative depending on whether @xmath309 is positive or negative and for @xmath310 , @xmath311 making @xmath305 negative . so the magnitude of @xmath305 should be such that @xmath312 . the problem here is that although we can calculate @xmath305 using eqn . ( [ dedtht ] ) @xcite using the parameters of the inner binary as mentioned earlier and varying @xmath313 , @xmath265 , @xmath299 and @xmath69 over realistic ranges satisfying conditions ( [ alpha_gr ] ) and ( [ alpha_ma ] ) , we can not calculate @xmath307 as the orientation of the spin axis of the pulsar with respect to the total orbital angular momentum is not known , which is needed to calculate @xmath307 ( see eqns . 8.58 , 8.82 and 8.91 of @xcite ) . moreover , the presently determined value of @xmath303 from timing analysis is @xmath314 which is merely the measurement uncertainty ( unpublished , provided by paulo freire through private communication ) . so this approach can not help us to test the hierarchical triple hypothesis at present . on the other hand , the observed value of the spin period derivative @xmath315 can be used to test the hierarchical triple scenario . a rough estimate for @xmath315 can be obtained by treating the inner binary as a single object of mass @xmath248 which forms a wide binary with stellar mass companion of mass @xmath69 @xcite . further , we let the projected semi - major axis of this new binary to be @xmath316 times that of the inner binary and choose a value for @xmath299 consistent with inequalities ( [ alpha_gr ] ) and ( [ alpha_ma ] ) . the associated line of sight acceleration leads to an estimate of @xmath317 of the order of @xmath318 and this is much higher than the reported value @xmath319 @xcite . this is fact seems to be a clear indication that this system is not the part of a hierarchical triple . there is an alternative hierarchical triple scenario @xcite , such that the original inner companion ( wd ) of the pulsar has been evaporated by now and we see only the outer binary at present with @xmath320 , @xmath321 , @xmath322 , @xmath323 , @xmath324 and @xmath325 days . this scenario is difficult to test as we do nt have any information about the parameters of the extinguished inner binary like @xmath68 , @xmath266 , @xmath326 and @xmath264 . in this case , the agreement between the measurement of the present day companion mass ( @xmath69 ) using @xmath38 and @xmath327 with the same using @xmath38 and @xmath37 is expected as @xmath327 is only due to general relativistic effect ( third term in eqn . [ dgdt ] ) because there is only one binary at present . let us now comment on the possible globular cluster origin for the system , motivated by the fact that in globular clusters , stellar interactions can impart eccentricity to millisecond pulsar binaries and indeed @xmath328 of the millisecond binaries in globular clusters have eccentricity @xmath329 . using the formalism discussed in the earlier section for fly - by interaction ( see [ eq : tfly2 ] ) , we find that the psr j1903 + 0327 like systems could have been produced in globular cluster systems up to a mean @xmath330 but not in any globular cluster with a higher value of this parameter . here we consider maximum allowed timescale for stellar interaction to be @xmath331 years as the characteristic age of the pulsar is @xmath332 years which is usually an upper limit of the true age of a radio pulsar @xcite . thus the putative origin of psr j1903 + 0327 inside a globular cluster could have taken place only in a restricted set of globular clusters . this further restricts the environment for production of such pulsars and therefore the overall probability for origin of this pulsar in a globular cluster must be smaller than that estimated by the dicoveres @xcite . here it is noteworthy to mention that the other types of eccentricity inducing interactions @xmath15 exchanges and mergers also scale with the parameter @xmath129 - so these interactions also can lead to psr j1903 + 0327 like systems only for a restricted set of globular clusters . so the eccentricity of this system still remains to be a puzzle to us . in this article we discuss how orbital parameters of binary radio pulsars reveal the history of their formation and evolution including dynamic interactions with other objects , the physics of the matter at extreme densities as inside the pulsar as well as the properties of the pulsar magnetosphere . firstly we try to understand the importance of studying dnss . if at least one of the ns of a dns is a radio pulsar , we can determine the moment of inertia of the pulsar through accurate radio timing analysis by measuring the extra advancement of the periastron of the orbit due to the spin - orbit coupling over the standard post - newtonian one . then by matching this observed value of the moment of inertia with the theoretically predicted value , one can constrain the dense matter eos . one necessary condition for this to be done is that the pulsar must be rapidly spinning and its companion ns must be much slower ; the double pulsar system psr j0737 - 3039(a / b ) seems to be the most potential candidate for this purpose till date as we know that psr j0737 - 3039a has @xmath333 ms whereas psr j0737 - 3039b has @xmath334 s. moreover the masses of both the nss are well determined . we also checked how good the system really is for this purpose by studying the effect of various parameters on the spin - orbit coupling term as a larger value of this term will facilitate the moment of inertia measurement . we found that this term has larger effect if the following conditions are satisfied - ( i ) short spin period ( ii ) short orbital period , ( iii ) high eccentricity . unfortunately , psr j0737 - 3039 lacks conditions ( iii ) and even ( i ) to some extent . so it will be nice if we can find better systems satisfying all the above conditions . globular clusters are potential sources for favorable dns systems in the above sense as dnss can be formed by exchange collisions due to the high stellar density and the abundance of millisecond pulsars in globular clusters . on the contrary , only one dns has been found in a gc so far which might be a result of selection effects as gcs are usually at larger distances in comparison to the disk pulsars . the resulting binaries are more probable to be highly eccentric with a millisecond pulsar facilitating moment of inertia estimation . we have also discussed how the study of the eclipse of the radio beam of psr j0737 - 3039a by the magnetosphere of psr j0737 - 3039b can be used as a tool to understand the magnetospheric properties of a pulsar in a better extent . some suggestive works about the formation of psr j0737 - 3039a / b have been mentioned too . we explain the presently observed orbital eccentricity and period data of gc binary pulsars by stellar interaction scenarios of fly - bys , exchanges and mergers with field stars . binaries with @xmath335 are most probably the result of exchange or merger events whereas binaries with @xmath336 are products of fly - by of single stars . a number of wide orbit intermediate eccentricity pulsars seen in the galactic disk are absent in the gc sample because they have been kicked up to relatively high eccentricities by passing stars in the dense stellar environments in gcs . in some gcs such as ter 5 , the stellar densities are so high , and the velocity dispersion so modest that the interaction timescale for exchange and fly - by interactions is relatively short . in such gcs a typical binary system may undergo multiple interactions . if the original binary contains a spun - up millisecond pulsar in a relatively soft " binary , then the exchange interaction may even produce a single millisecond pulsar in the cluster . this may explain the higher incidence of isolated millisecond pulsars in gcs compared to that in the galactic disk @xcite ; in gcs 52 out of 59 isolated pulsars are millisecond pulsars whereas in the disk 23 out of 1565 isolated pulsars are millisecond pulsars . in addition , exchange interactions , as we have seen , can lead to highly eccentric orbits and the system can be ejected from the cluster core . if the last encounter took place not too long ago , the system can be at a relatively large offset from the cluster core , albeit being still spatially co - located with the gc . we have found that the eccentricity of psr b1638 + 36b ( in m13 ) is difficult to explain by any type of interactions - fly - by , exchange or merger . so we propose that either its true eccentricity is lower than the presently known upper limit or it is a member of a hierarchical triple . we have also considered the effects of collision induced ionization on the present day distribution of orbital parameters of radio pulsars in gcs . in the galactic disk we find 12 pulsars with @xmath337 days ( although few of them have more massive companions than the pulsar binaries in the gcs ) , while there are only 3 pulsars in this range of orbital period . although it is tempting to speculate that these systems are missing from the present day gcs because they have been ionized in the past , we find that the ionization probability becomes substantial in this orbital period range only for very small values of companion masses . observational selection effects can be the cause of this discrepancy between the number of large orbital period pulsars in the disk in comparison to that in gcs . many galactic disk binary pulsars are seen in the region of @xmath194 plane predicted by phinney due to the fluctuation dissipation of convective eddies and the resultant orbital eccentricities that are induced . these pulsars are missing from the gc sample . there is no reason not to expect these systems to form in the gcs ( although due to the lower metallicity of the stellar companions in gcs , they are expected to be in slightly different region in the @xmath194 plane ) . this can be explained by the substantial probability of them being knocked out of their original phase space due to stellar interaction in gcs . indeed there are some wide binaries in the present day gcs with moderately high eccentricities ( e.g. @xmath338 and @xmath339 ) which could have arisen out of fly - bys or exchanges from progenitor binaries with relic " eccentricities @xmath340 ( merger in unlikely because of moderately low values of @xmath33s ) . the circularity of group iii pulsars in gcs are thought to be due to either their special formation channels and young age or due to their locations at the outskirts of the gcs . psr j1903@xmath1050327 is the only one eccentric millisecond pulsar in the galactic disk discovered so far . its millisecond spin - period suggests the spin - up scenario through accretion in the past . as such recycled pulsars are expected to be in circular orbits due to tidal - coupling induced circularization , this system has created lots of interest among pulsar researchers . as it is well known that in globular clusters , stellar interactions can impart eccentricity to an initially circular orbit , the possibility of past gc association of this system have been studied and almost rejected . moreover , the possibility of this system being a member of a hierarchical triple system also seems to be less unlikely . so this system remains an open question for us . we hope in the future with more advanced technologies like ska , many more new interesting types of pulsars will be discovered and that the exciting and challenging situation will ultimately lead to a better understanding of the physics of pulsars . this article uses some of the results of the collaborative works with alak ray and achamveedu gopakumar whom the author wishes to thank . the author also thanks michael kramer and paulo freire for discussions ; bhaswati bhattacharyya and ranjeev misra for comments on the manuscript .
orbital parameters of binary radio pulsars reveal the history of the pulsars formation and evolution including dynamic interactions with other objects . advanced technology has enabled us to determine these orbital parameters accurately in most of the cases . determination of post - keplerian parameters of double neutron star binaries ( especially of the double pulsar system psr j0737 - 3039 ) provide clean tests of the general theory of relativity and in the future may lead us to constrain the dense matter equations of state . for binary pulsars with main - sequence or white dwarf companions , knowledge about the values of the orbital parameters as well as of the spin periods and the masses of the pulsars and the companions might be useful to understand the evolutionary history of the systems . as accreting neutron star binaries lead to orbit circularization due to the tidal coupling during the accretion phase , their descendants @xmath0 binary millisecond pulsars are expected to be in circular orbits . on the other hand , dense stellar environments inside globular clusters cause different types of interactions of single stars with pulsar binaries like fly - by " , exchange " , and merger " . all these interactions impart high eccentricities to the pulsar binaries . so it is quite common to get eccentric millisecond pulsar binaries in globular clusters and we find that fly - by " causes intermediate values of eccentricities while exchange " or merger " causes high values of eccentricities . we also show that ionization " is not much effective in the present stage of globular clusters . even in the absence of such kinds of stellar interactions , a millisecond pulsar can have an eccentric orbit as a result of kozai resonance if the pulsar binary is a member of a hierarchical triple system . psr j1903 + 0327 is the only one eccentric millisecond pulsar binary in the galactic disk where stellar interactions are negligible . the possibility of this system to be a member of a hierarchical triple system or past association of a globular cluster have been studied and found to be less likely . @xmath1 inter university centre for astronomy and astrophysics , pune 411 007 , india + @xmath2 [email protected]
measurement of luminal pressure - induced neurogenic contraction of whole intestine in ex vivo : luminal pressure - induced neurogenic contraction of whole intestine was measured as described previously . briefly , the mid colon and terminal ileum ( about 3 cm ) were isolated from c57bl/6 mice and flushed of luminal contents . the samples were cannulated and placed in water - jacked organ bath in modified physiological salt solution ( pss ; containing nacl 136.9 mm , kcl 5.4 mm , mgcl2 1.0 mm , cacl2 1.5 mm , nahco3 23.8 mm , glucose 5.5 mm and edta 0.01 mm at ph 7.4 ) at 37c in a 95% o25% co2 atmosphere . the contraction was measured using a mdl 1401 magnetic blood flow meter ( skalar , breda , the netherlands ) equipped with computerized powerlab system ( ad instruments , colorado springs , co , u.s.a . ) . frequency of peristalsis like neurogenic motility , maximum amplitude of peristalsis like neurogenic motility and total motility index ( total luminal flow ) for 15 min were analyzed . total motility index was estimated by calculating the area under the curve ( auc ) of one neurogenic motility by luminal pressure . measurement of intestinal transit in vivo : intestinal transit in vivo was measured by luminal content labeled with phenol red [ 13 , 17 ] . briefly , after 18 hr of fasting , the mice ( c57bl/6 , male , 812 weeks age , 12 light - dark cycles ) were orally administered 0.25% ( w / v ) phenol red in 5% ( w / v ) glucose via a gastric tube . one hour after administration , the gastrointestinal tract was isolated and divided into 15 ( stomach ; sto , small intestine ; si1-si10 , cecum ; sec and colon ; co1-co3 ) segments at equal intervals . the volume of phenol red in each segment and the geometric center of distribution were calculated as previously described [ 13 , 17 ] . model mice of poi : poi is one of major diseases of gastroenterological surgery with gastrointestinal motility disorder [ 9 , 16 , 20 ] . recent works revealed that inflammation of intestinal smooth muscle layer is pathogenesis of poi [ 13 , 17 ] . recruited monocyte derived macrophages , neutrophils and activated resident macrophages are considered important causal agents for generating poi . in the present study , we used model mice of poi to analyze anti - inflammatory action of maropitant . after median section , the distal ileum was exteriorized and then gently scraped three times with a sterile moist cotton applicator ( intestinal manipulation ; i m ) . the mice were sacrificed , and the ilea were isolated 24 hr after i m . maropitant ( 1 , 3 , 5 or 10 mg / kg ) was administered subcutaneously 1 hr before i m . immunohistochemistry and histochemistry : whole mount ileal muscularis preparations were prepared as described previously . for immunohistochemistry analysis , samples were washed twice with tbs for 30 min and then permeabilized with 0.2% triton - x-100 at room temperature for 90 min followed by blocking with 2% bsa in tbs at room temperature for 30 min . the samples were then incubated with primary antibody ( rabbit anti - human pgp9.5 polyclonal antibody , 1:1,000 ; cosmo bio co. , ltd . , tokyo , japan ; and rat anti - mouse cd68 antibody , 1:500 ; serotec , dusseldorf , germany ) overnight at 4c . after washing , the samples were incubated with secondary antibody ( alexa568 goat anti - rabbit igg , 1:500 ; invitrogen , carlsbad , ca , u.s.a . ; and alexa488 donkey anti - rat igg , 1:500 ; molecular probes inc . , eugene , or , u.s.a . ) at room temperature for 1.5 hr . after washing secondary antibody , the samples were examined with a confocal microscope ( eclipse ti ; nikon , tokyo , japan ) . in histochemistry analysis , the number of cd68 positive cells and mpo positive cells were counted in four randomly selected areas of each preparation , and the average number of these cells was calculated . statistical analysis : data were statistically evaluated with an unpaired student s t - test for comparisons between two groups and with one - way anova followed by tukey s test for comparisons among three or more groups . effect of maropitant on luminal pressure - induced neurogenic motility of whole intestine in ex vivo : as shown in fig . 1afig . 1.effect of maropitant on the luminal pressure - induced neurogenic motility of whole intestine in ex vivo . a : typical result out of 5 independent experiments in mid colon . left or right panel showed a typical result in the absence or presence of maropitant ( 1 m ) , respectively . whole colon tissue was treated with maropitant for 15 min before measurement of the motility . b : frequency of peristalsis like neurogenic motility for 15 min in mid colon . c : maximum amplitude of peristalsis like neurogenic motility for 15 min in mid colon . each column showed mean sem . * and * * showed p<0.05 and p<0.01 vs vehicle , respectively . , luminal pressure ( 5 cm h2o ) elicited rhythmic luminal flow in a reflection of contraction and relaxation of mid colon . this rhythmic motility was completely abolished by tetrodotoxin ( 100 ng / ml ; n=4 , data not shown ) , suggesting that the luminal pressure - induced intestinal motility is neurogenic motility via submucosal / myenteric plexus neural system as previously reported . in the mid colon of control mice , slow and big waves of luminal flow were observed based on fast and small waves of luminal flow . maropitant ( 100 nm10 m ) modulated the neurogenic motility in a concentration - dependent manner ( fig . maropitant decreased the big waves of luminal flow and also decreased amplitude , resulting in increased frequency of the neurogenic motility ( fig . to reflect these changes , total motility index assessed by auc was inhibited ( fig . 1d ) . in the terminal ileum , luminal pressure induced rhythmic luminal flow in a reflection of contraction and relaxation maropitant also decreased the rhythmic luminal flow , resulting in the decreased total motility index as shown in fig . effect of maropitant on the luminal pressure - induced neurogenic motility of whole intestine in ex vivo . a : typical result out of 5 independent experiments in mid colon . left or right panel showed a typical result in the absence or presence of maropitant ( 1 m ) , respectively . whole colon tissue was treated with maropitant for 15 min before measurement of the motility . b : frequency of peristalsis like neurogenic motility for 15 min in mid colon . c : maximum amplitude of peristalsis like neurogenic motility for 15 min in mid colon . each column showed mean sem . * and * * showed p<0.05 and p<0.01 vs vehicle , respectively . effect of maropitant on intestinal transit in mice : we measured transportation of luminal contents labeled with phenol red within 1 hr after oral administration . in control healthy mice , approximately 5% of luminal content remained inside the stomach , whereas , approximately 75% was transported down the distal ileal part ( si7-si10 ) as shown in fig . 2afig . 2.effect of maropitant on intestinal transit in in vivo . intestinal transit 1 hr after administration of phenol red was measured in vivo . a : distribution of luminal content labeled with phenol red in segmented gastrointestine with or without maropitant . maropitant ( 10 mg / kg ) was subcutaneously given 30 min before administration of phenol red . b : geometric center values were calculated from a. each column showed mean sem ( n=4 each ) . * showed p<0.05 vs control .. on the other hand , in maropitant ( 10 mg / kg , sc)-treated mice , approximately 15% of luminal content remained inside the stomach , and the 85% was transported down the intestine . however , the transported luminal content inside the small intestine showed a wide distribution with several peaks ( si4 , si8 and si10 ) . maropitant significantly decreased geometric center value , indicating average distribution of luminal content as shown in fig . 2b ( control ; 8.29 0.55 , maropitant ; 5.78 0.80 , p<0.05 ) . intestinal transit 1 hr after administration of phenol red was measured in vivo . a : distribution of luminal content labeled with phenol red in segmented gastrointestine with or without maropitant . maropitant ( 10 mg / kg ) was subcutaneously given 30 min before administration of phenol red . b : geometric center values were calculated from a. each column showed mean sem ( n=4 each ) . * showed p<0.05 vs control . effect of maropitant on leukocytes infiltration in poi model mice : in model mice of poi , muscularis inflammation with motility disorder is main symptom . cd68-positive macrophages and mpo - stained neutrophils infiltrated into myenteric plexus and serosal regions in the inflamed intestinal smooth muscle layer . in this experiment , we could confirm the leukocytes infiltration at 24 hr after i m ( neutrophils : control ; 0 0 , i m ; 803.04 58.76 , p<0.01 . maropitant ( 1 mg / kg10 mg / kg ) had no effect on neutrophils infiltration by i m ( fig . 3afig . 3.effects of maropitant on leukocytes infiltration into the intestinal smooth muscle layer in mice model of poi . effect of maropitant on mpo - positive neutrophils infiltration ( a ) and cd68-positive macrophages infiltration ( b ) by i m . maropitant ( 1 , 3 , 5 or 10 mg / kg ) was subcutaneously administered 30 min before i m . detailed method for quantification of cells number was shown in the materials and methods . maropitant ( 1 or 3 mg / kg ) tended to decrease cell number of infiltrated macrophages , but these effects were not significantly different ( fig . 3b ) . maropitant ( 5 or 10 mg / kg ) had no effect on the macrophages infiltration by i m . effects of maropitant on leukocytes infiltration into the intestinal smooth muscle layer in mice model of poi . effect of maropitant on mpo - positive neutrophils infiltration ( a ) and cd68-positive macrophages infiltration ( b ) by i m . maropitant ( 1 , 3 , 5 or 10 mg / kg ) was subcutaneously administered 30 min before i m . detailed method for quantification of cells number was shown in the materials and methods . maropitant is a selective nk1r antagonist , which is a new anti - emetic drug for dogs . recommended dosage of maropitant is 1 mg / kg sc or 2 mg / kg orally once daily for up to 5 consecutive days for acute emesis and 8 mg / kg orally once daily for up to 2 consecutive days for motion sickness of dogs . another pharmacokinetics study by using gerbil estimated that plasma concentration ranges of maropitant at 2 or 4 hr after the administration ( 1 mg / kg sc ) are 10.025.5 ng / ml , that are calculated to 14.7 m37.6 m . in this study , dosages of maropitant we used are 1 to 10 mg / kg sc in in vivo and 1 to 10 m in ex vivo , indicating that concentrations used in this study are dosages within clinical use . nk1r is expressed in various kinds of cells in murine intestine [ 4 , 19 ] . nk1r is located on cholinergic neurons , nitrergic neurons , icc and smooth muscle cells . in general , all nkrs , especially nk1r , are involved in non - adrenergic and non - cholinergic neuronally mediated contractions of circular muscle layer of the intestine . in contrast , it was reported that sp inhibited intestinal peristalsis and gastric activity through nitrergic inhibitory myenteric neuron by stimulating nk1r . in this study , the luminal pressure - induced neurogenic motility in ex vivo was measured by using isolated mid colon and terminal ileum . submucosal / myenteric nervous system is important to detect luminal pressure , which in turn induced neurogenic peristalsis like motility . maropitant inhibited the neurogenic motility elicited by luminal pressure , suggesting that maropitant induced motility disorder in whole intestine in ex vivo . we further investigated the effect of maropitant on intestinal transit in in vivo by measuring transportation of luminal content labeled with phenol red . results indicated that maropitant delayed geometric center value . in the ex vivo experiment to measure the luminal pressure - induced neurogenic motility , maropitant increased frequency of motility whereas decreased the amplitude , indicating hyperactivity of the neurogenic motility . the segmented luminal content labeled with phenol red in maropitant - treated mice in in vivo may be caused as the results of hyperactivity . taken together , maropitant caused motility disorder relatively at high concentration range in mice ileum and colon , although detailed mechanism of maropitant to induce intestinal dysmotility in in vivo was not identified in this study . another function of sp / nk1r signaling is pro - inflammatory effects on various inflammatory diseases [ 15 , 21 ] . sp produced from t cells , macrophages , dendritic cells and eosinophils can activate nk1r on t cells , which in turn produce ifn- to lead to mucosal inflammation in the gastrointestinal tract . nk1r antagonist ameliorates the inflammation in trinitrobenzene sulfonic acid - induced colitis and the non - steroidal anti - inflammatory medication - induced intestinal inflammation in il-10 null mice [ 1 , 22 ] . these reports lead to a hypothesis that maropitant may have an anti - inflammatory action to prevent gastrointestinal inflammatory diseases . however , in the murine model of poi , maropitant did not prevent leukocytes infiltration by i m , concluding that maropitant does not have an anti - inflammatory action in mice . leffler and colleague reported that nkrs differ to a large degree among animal species with respect to their affinities for antagonists . they cloned nkrs from gerbil , mice , rat , dog and human and transfected those receptors into cho cells to compare affinity of nkrs antagonists . they concluded that dog nk1r had similar pharmacological characteristics for nk1r antagonists with nk1r of human and gerbil , but different characteristics compared with nk1r of mice and rat . in this report , a selective nk1r antagonist , an aprepitant , that is an anti - emetic drug for human , is clearly less potent at rat nk1r than at nk1r from dog , human and gerbil . as maropitant is a potent anti - emetic drug for dogs , it will be possible that maropitant may have weak affinity for mice nk1r rather than dog , human and gerbil nk1rs . as emesis has not been observed in common laboratory animals including mice , we could not evaluate anti - emetic efficacy of maropitant to mice by using substitute methods . so , it still remained as unsolved issues whether motility disorder mediated by maropitant is adverse effect or not in mice . further detailed investigation will be necessary to clarify effects of maropitant on gastrointestinal motility and inflammation by using another laboratory animals and/or dogs . in conclusion , maropitant induced motility disorder in ileum and colon ex vivo and in vivo in mice . maropitant did not show significant anti - inflammatory action assessed by using model mice of poi .
maropitant is a neurokinin 1 receptor ( nk1r ) antagonist that is clinically used as a new anti - emetic drug for dogs . substance p ( sp ) and its receptor nk1r are considered to modulate gastrointestinal peristalsis . in addition , sp works as an inflammatory mediator in gastrointestinal diseases . aim of this study is to clarify the effects of maropitant on intestinal motility and inflammation in mice . ex vivo examination of luminal pressure - induced intestinal motility of whole intestine revealed that maropitant ( 0.110 m ) increased frequency of contraction , decreased amplitude of contraction and totally inhibited motility index in a concentration - dependent manner . we measured intestinal transit in vivo by measuring transportation of orally administered luminal content labeled with phenol red . our results demonstrated that maropitant ( 10 mg / kg , sc ) delayed intestinal transit . geometric center value was significantly decreased in maropitant - treated mice . anti - inflammatory effects of maropitant against leukocytes infiltration into the intestinal smooth muscle layer in post - operative ileus ( poi ) model mice were measured by immunohistochemistry . in poi model mice , a great number of cd68-positive macrophages or mpo - stained neutrophils infiltrated into the inflamed muscle region of the intestine . however , in the maropitant treated mice , the infiltration of leukocytes was not inhibited . the results indicated that maropitant has ability to induce disorder of intestinal motility in mice , but has no anti - inflammatory action in the mouse of a poi model . in conclusion , in mice , maropitant induces disorder of intestinal motility in vivo .
During the superbly absurd adventures of a suburban couple in "Date Night," a pair of thugs contemplates the husband and wife with bafflement. "These two," one thug says to the other, "are not at all what they seem." That is true, for reasons too intricate to explain here. It's equally true that the thugs are not what they seem. Happily, however, the movie's stars, Steve Carell and Tina Fey, are exactly what they seem. They're perfect casting in a short, sweet comedy that makes the most of their genial gifts until it loses its sense of proportion. Watch a scene from "Date Night," starring Tina Fey and Steve Carrell as a married couple who stumble into a series of misadventures while having a night on the town. Courtesy 20th Century Fox. Mr. Carell is Phil Foster, a tax accountant; Ms. Fey is Claire Foster, a real estate broker (and a realist who, in the current market, drops the price of one of her listings from $1.8 million to $320,000). They live with their two children in Teaneck, N.J., where they try to keep love, if not passion, alive by going on weekly dates to a local restaurant. One of the rituals they enjoy during these ritual dinners is observing couples at other tables and acting out fanciful versions of what they might be saying. Funny in their own right, those little improvs also prepare us for the flipped-out verve that Phil and Claire manage to muster following a visit to a much fancier restaurant in Manhattan. There, in a cheerful imitation of a Hitchcock plot, they're mistaken for a couple who've done something dangerous, then forced to run for their lives. View Full Image Twentieth Century Fox Tina Fey and Steve Carell as a couple on the run in 'Date Night.' Watching these two intensely likable comedians work together is a special pleasure. What binds them isn't chemistry, exactly—Josh Klausner's witty screenplay takes note of the Fosters' minimal sex life—but a kind of algebra that resolves outlandish problems. Phil, an endearing hick who could be a nebbish if he played his cards wrong, gets to channel Walter Mitty and play action hero. Claire, an attractive woman with an overdeveloped sense of understatement, turns into a hottie who passes for a gum-chewing gun moll even though she doesn't have any gum. And the director, Shawn Levy (of the "Night at the Museum" franchise), complements their antics with deft work by a supporting cast that includes Mark Wahlberg as a superstud security expert, and James Franco and Mila Kunis as a low-life duo named Taste and Whippit. The comedy turns coarse during a garishly overproduced car chase. (Ditto for the broadness of William Fichtner's dissolute district attorney.) That's a pity, but hardly a mystery. Under pressure from less expensive forms of entertainment, the studios fear that small-scale films—even distinctive little films like this one—won't find an audience unless they're bulked up with production values. (And a car chase in the trailer will surely sell tickets.) Not to worry, though. "Date Night" is too good to be wrecked by reckless driving. 'After.Life' Women often wear their hearts on their sleeve, and even hatless men can go hat in hand. But one of the many repellent firsts in this dreadful, singularly squirmful horror flick is a woman with her heart in her hand, standing in a shower à la Janet Leigh. "After.Life" is a disquisition on life, death, the boundary in between and Christina Ricci's naked bod as she lies, undead and unquiet, on the stainless steel table of an undertaker named Eliot Deacon (Liam Neeson). Theirs is a special relationship that goes beyond corpse and embalmer. Refusing to believe that she has perished in an automobile accident, Ms. Ricci's Anna struggles, sometimes quite frighteningly, to escape Deacon's clutches. "I'm not dead!" she insists, but he will have none of it. "You're in denial," he tells her before basting her face with needle and thread. When Anna persists, Deacon turns churlish. "You're a corpse," he says. "Your opinion doesn't matter any more." It's the final insult before the ultimate putdown. A carefully crafted debut feature, "After.Life" was directed by Agnieszka Wojtowicz-Vosloo from a script she wrote with her husband, Paul Vosloo, and Jakub Korulczuk. The film really does deal with life and death, in its sententious way, and some of its images of imprisonment—not to mention injection and evacuation—stay with you, like it or not. But the dialogue is clumsy, the tone swings between somber and silly and the whole bizarre venture eventually succumbs to rigor mortis. *** Last week I devoted nearly half of my negative review of "Clash of the Titans" to various complaints about the 3-D process in which the film was displayed. Thereby hangs another tale with additional dimensions. Thanks to the runaway success of "Avatar," and its stunningly vivid 3-D version, Hollywood is suddenly chasing depth-via-glasses with a fervor bordering on the fanatical. Not only is 3-D being hailed as the solution to the industry's ills, but movies already shot with conventional cameras are hurriedly being reprocessed into stereo simulations. The two big ones so far are "Alice in Wonderland" and "Clash of the Titans. In Disney's "Alice," the depth effect is noticeable but unexceptional. In "Clash" the effect was, to my eyes, negligible at best and maddening at worst, since the glasses seemed to be soaking up most of the light from the screen. The first hint of something wrong—not with my eyes, I hasten to say—came only minutes after my review went online. Several readers emailed accounts of the same murky experience. One of them was from an online film critic, Wayne Melton, who guessed correctly that he'd seen the movie at the same screening I attended, in a Hollywood multiplex with a reputation for excellent projection. Unlike me, however, he realized that the problem might have been the battery-powered glasses: I never stopped to think that my glasses contained a battery. He got another pair from an usher, put them on and, lo and behold, saw a bright 3-D effect as advertised. (The movie itself, he agreed, was "appalling.") The next day brought an email—a remarkably collegial one, under the circumstances—from Michael Fink, the CEO of Prime Focus, the company that did the "Clash of the Titans" conversion. With a mixture of consternation and perplexity prompted by my harsh review, Mr. Fink invited me to visit the company's Hollywood offices and see sample scenes of the film as it had been delivered to the studio. I did so earlier this week, and got an eyeful—two eyefuls, strictly speaking—plus an impromptu education from Rob Hummel, the man in charge of Prime Focus's postproduction. The scenes I viewed were indeed bright, with an impressive illusion of depth. They were also surprisingly strong in what Mr. Hummel called volumetrics—the illusion of volume that can make a ball look like a ball, rather than a disk. Clearly the glasses had been at fault. And my experience, as it turned out, was only one of many. At a different preview screening last week, spectators saw "Clash of the Titans" film inverted—not upside down, but with left and right images switched by out-of-phase projectors, so that distant objects seemed close and vice versa. Confronted by such visual confusion, said Michael Fink in a subsequent email, "some people's brains explode." What, then, does all of this say about the 3-D tide that's sweeping the industry? Given the right occasion, 3-D can enhance the viewing experience dramatically. So can the sort of after-the-fact stereo simulation provided by Prime Focus and its 20 or more competitors in an increasingly crowded field. But 3-D technology is complex in the production (or postproduction) phase, and far from simple when it comes to exhibition, whether theaters opt for a system that uses so-called active-shutter glasses with built-in electronics or passive glasses that polarize the light passing through them. The industry as a whole is only beginning to address the consequences of that complexity. Remarkably, the same studios that are spending vast sums to produce 3-D films have thus far ceded responsibility for their proper projection to the theater chains and theater employees. For a moviegoer, the fate of a blockbuster could be riding on the voltage of a tiny button battery. And what occasions are right for 3-D in the first place? The same ones that have been right for 2-D all along. Compelling stories, well told. Characters worth caring about. Actors practicing their craft with variety and vitality. Filmmakers reveling in the possibilities of the movie medium and the joys of showmanship. Confronted by movies that lack such basic strengths, many people's brains turn off. DVD FOCUS 'After Hours' (1985) Instead of a suburban couple going from Teaneck to New York, Martin Scorsese's paranoid fantasy focuses on Paul Hackett (Griffin Dunne), a young word-processor—that's what they called them back then—in midtown Manhattan who goes down to Soho for a late-night date and finds himself trapped in urban madness. The marvelous cast includes Rosanna Arquette, Verna Bloom, Linda Fiorentino, Teri Garr, John Heard, Dick Miller, Will Patton and Catherine O'Hara. Cinematography by Michael Ballhaus. The writer of record is Joseph Minion, who happens to have been born in Teaneck. 'The Vanishing' (1988) If I told you why George Sluizer's Dutch thriller was brought to mind by "After.Life," I'd be spoiling one of the most effective—and deeply creepy—endings in movie thrillerdom. (Don't confuse this film with its inferior English-language version that Mr. Sluizer directed five years later.) The plot—seldom has a term been more chillingly apt—concerns two men. The younger one, Rex, searches obsessively for his girlfriend after she disappears from a highway rest stop. The older one, Raymond, is her diabolically forthcoming abductor. 'Clash of the Titans' (1981) Check out the original to see how far we've come, mostly in the wrong direction. No one in his right mind would hold this up as a paragon of film production. The writing is naïve without being charming, and the acting is variable, to use a charitable term. But the cast, an enjoyable collection of mismatches, includes Laurence Olivier, Flora Robson, Burgess Meredith, Harry Hamlin, Claire Bloom, Siân Phillips, Ursula Andress and Maggie Smith. The movie's star, of course, is Ray Harryhausen, the stop-motion maestro who created the still-endearing special effects. --Joe Morgenstern Write to Joe Morgenstern at [email protected] ||||| He might be bound to The Office for now, but it's on the big screen where he truly makes our guts ache. Steve Carell doesn't have a face for the movies. It's too plain, too pale, like a weatherman from New Jersey, which is how he landed a supporting role in Anchorman. His features don't carry the comical devilishness of Jim Carrey, or even the mischievousness of an Adam Sandler or Will Smith. If you were to run into him on a street corner, oblivious to his fame, you wouldn't turn back for a second. He's too ordinary to make a lasting impression. SUBSCRIBE All of this might work to his favor on the small screen, where he plays the clueless boss Michael Scott on The Office. It should backfire on the big screen, where everything is epic now, and so 3-D. But comedy isn't a branch of mathematics—the formula actually works in reverse. The Office might have the critical backing and the Emmys, but it's a dwindling import that nobody will talk about in 10 years (do they still even talk about it now?). It's on the big screen that Carell has made his mark, from The 40-Year-Old Virgin to Get Smart. Which brings us to the latest example, Date Night. The premise is like Charlie's Angels without the angels: a New Jersey husband (Carell) and wife (Tina Fey) go out for a peaceful dinner in Manhattan, are somehow mistaken for a couple blackmailing a corrupt district attorney, and spend the rest of the night on the run. If the stars had been—for example—Jennifer Aniston and Gerard Butler, it wouldn't be worth catching even on TBS. But Carell is such the unusual film actor (he got his start on The Daily Show, after all) that he can make even the most mundane line pop. He's also unmatched when it comes to physical comedy—i.e., the chest waxing in the 40-Year-Old Virgin. Paired with Tina Fey (a writer who also played a fake anchor on Saturday Night Live), the movie easily succeeds as mainstream popcorn entertainment. Has there been any other comedian at the movies who continuously takes a tired premise and makes it so delicious, your gut hurts? (Or maybe it hurts from all the laughing.) Because Carell has such a gentle onscreen presence, he brings out the best in his female leads. Who knew that Anne Hathaway had action-babe potential before Get Smart? Or that Catherine Keener could be so Julia Roberts–lovable in Virgin? He also transformed the normally dramatic Juliette Binoche in Dan in Real Life, a better romantic comedy than anything Hugh Grant has done in the last 10 years. In Date Night, Carell is the cake batter that holds up Fey's icing. Their breezy banter is a throwback to old-fashioned movie stars, which is funny, since she's not a conventional movie star either. When she cast herself opposite longtime friend Amy Poehler in Baby Mama, it was like watching an endless SNL skit. Carell might not get the onscreen recognition that he deserves—yet—but give him time. Like Ben Stiller, he's a thinking man's comic, with the potential for crossing over into drama. Stiller is now getting rave reviews for his performance as a tortured man-boy in the Noah Baumbach film Greenberg. But it doesn't seem so great when you compare it to what Steve Carell accomplished in Little Miss Sunshine. When Carell's character appears at the start of the movie, with bandages around his wrists from an apparent suicide attempt, his eyes are full of sorrow in a way that almost makes you take a step back. Who knew that Steve Carell had such range? If he ever takes on Hamlet, sign me up for a front-row seat. © 2010
– In Date Night, married suburbanites Phil (Steve Carell) and Claire Foster (Tina Fey) go for dinner in Manhattan and, through a series of predictably absurd twists, end up dodging thugs and crashing cars. This comedy-action hybrid doesn't win points for originality, but is saved—for some critics, just barely—by its talented and likeable stars. TIME calls this flick "a lively, often astute piece of marital sociology." This "cinematic happy hour for Mom and Dad" doesn't even "need a pulse to draw an audience," writes Mary Pols. Luckily, she says, it has one. Date Night succeeds as "popcorn entertainment" because Steve Carrell manages to "take a tired premise and make it so delicious, your gut hurts," writes Ramin Setoodeh on Newsweek. Fey and Carell turn predictable twists into "superbly absurd adventures," says Joe Morgenstern in the Wall Street Journal. Though the car chases are over-produced, the film is "too good to be wrecked by reckless driving." The New York Times, however, was not amused. "About that plot: who cares?" asks A.O Scott. Date Night is "superior to most recent movies of its kind, the marital action comedy," he writes. But frankly, "that's not saying much."
hyperglycemia is a common adverse outcome in critically ill patients ; it is associated with high mortality rates and occurs in individuals with and without a previous history of diabetes . in addition , glucose is the main energy source for cancer cells , with the long hyperglycemic state providing a nutrition base to promote cancer cell differentiation and growth . as a means of nutrition supply , especially for abdominal surgery patients , total parenteral nutrition ( tpn ) prevents nutrition loss after surgery , and improves survival rate and quality of life . in 2005 , cheung et al . reported that hyperglycemia is a predictor of poor outcomes in tpn . the confirmation of a relation between blood glucose ( bg ) levels and adverse outcomes supports a tight glycemic control in these patients . in 2010 , pasquel et al . collected the bg data in three parts , that is , pre - tpn ( before 24 h ) , within 24 h , and during days 210 of tpn for patients , for 1 year , and concluded that hyperglycemia is associated with increased hospital complications and mortality . they also pointed out that bg values pre - tpn and within 24 h of initiation of tpn are better predictors of hospital mortality and complications compared with the mean bg level during the entire duration of tpn . therefore , how the bg fluctuates in various types of the tumor with tpn is an open question . another unanswered question concerns the factors that influence bg under tpn . to the best of our knowledge , no report regarding the relations of bg with different tumor types in patients receiving tpn has been published . to address these questions , we performed a retrospective study to determine the relations among these factors in tumor patients . we performed a retrospective case - control study to assess tumor patients in cancer hospital / institute , chinese academy of medical sciences , from january 2013 to december 2014 to evaluate the effect of tpn on bg after surgery . tumor patients entered the study on the 1 day of tpn infusion , and bg values were recorded at least every 6 times per day after tpn infusion . the study was approved by the ethics committee of cancer hospital / institute , chinese academy of medical sciences , and written informed consent was obtained from each patient . this work involved surgery patients receiving tpn during the calendar year of 2013 and 2014 in cancer hospital / institute , chinese academy of medical sciences . patients were excluded with one of these criteria : ( 1 ) tpn not being the unique nutrition source ; ( 2 ) tpn duration shorter than 2 days ; ( 3 ) use of anti - tumor drugs after surgery ; ( 4 ) no surgery . therapeutic schemes : for tumor patients , a transfusion apparatus was applied and nutrients were delivered intravenously through the central venous catheter 1820 h / d , with a transfusion speed of 12 mlkgd . the one touch ultra vue glucometer ( johnson and johnson , usa ) was used to collect bg levels 6 times per day ( interval survey 6 h during each time ) during the whole tpn infusion . the average bg values within 24 h were considered bg levels for a giving day . blood glucose levels were divided into three parts : pre - tpn , within 24 h , and 210 days after 24 h. two - sample wilcoxon 's tests were used to compare the demographic and clinical characteristics between diabetic and nondiabetic groups . this work involved surgery patients receiving tpn during the calendar year of 2013 and 2014 in cancer hospital / institute , chinese academy of medical sciences . patients were excluded with one of these criteria : ( 1 ) tpn not being the unique nutrition source ; ( 2 ) tpn duration shorter than 2 days ; ( 3 ) use of anti - tumor drugs after surgery ; ( 4 ) no surgery . therapeutic schemes : for tumor patients , a transfusion apparatus was applied and nutrients were delivered intravenously through the central venous catheter 1820 h / d , with a transfusion speed of 12 mlkgd . the one touch ultra vue glucometer ( johnson and johnson , usa ) was used to collect bg levels 6 times per day ( interval survey 6 h during each time ) during the whole tpn infusion . the average bg values within 24 h were considered bg levels for a giving day . blood glucose levels were divided into three parts : pre - tpn , within 24 h , and 210 days after 24 h. two - sample wilcoxon 's tests were used to compare the demographic and clinical characteristics between diabetic and nondiabetic groups . pictures were drawn with microsoft excel professional 2013 . a p < 0.05 was considered to be statistically significant . demographic characteristics are summarized in table 1 . a total of 312 patients averaging 58.6 11.1 years , including 61.9% men ( body mass index [ bmi ] , 24.2 3.6 kg / m ) . all individuals received tpn after surgery with a mean duration of 7.5 3.0 days . six tumor types were selected : hepatic carcinoma ( hc , 21.8% ) , rectal carcinoma ( rc , 17.3% ) , colon carcinoma ( cc , 14.7% ) , gastric carcinoma ( gc , 29.8% ) , pancreatic carcinoma ( pc , 11.5% ) , duodenal carcinoma ( dc , 4.8% ) . main characteristics of tumor patients bmi : body mass index . the mean bg level during tpn was 9.2 2.2 mmol / l ; it was 6.1 mmol / l within 24 h. interestingly , mean bg levels returned to 9.0 2.4 mmol / l from 24 h till the end of the tpn infusion . as bg levels are greatly influenced by diabetes in patients [ table 2 ] , the master sample was divided into two groups , including diabetic and nondiabetic patients . therefore , all subsequent comparisons were based on these two subgroups to avoid the diabetes factor . mean bg values in different periods , mmol / l bg : blood glucose ; tpn : total parenteral nutrition . total parenteral nutrition infusion patients were divided into two groups respectively , according to insulin usage status or diabetes disease . the f - test indicated no statistical difference in tpn glucose content between groups . in the diabetic group , bg levels in hc patients varied considerably , and highest values were obtained for all tumor kinds . bg variations in pc patients were the least , with minimal change within 24 h ; meanwhile , the changes in dc were the most pronounced . variations of bg levels in cc patients were close to those of gc and rc , and values were very small . in the nondiabetic group , with increasing bg values , dc , hc and cc were more represented than other tumor types in this sequence in diabetic individuals , as well as in the nondiabetic group . both the increasing and decreasing bg ranges in dc and hc were large in the two subgroups . for patients with decreasing bg range after 24 h , all tumor types decreased faster in the nondiabetic group compared with diabetic individuals . decreasing bg ranges in dc , cc and gc were higher than those obtained for the other three tumor kinds . in the nondiabetic group , bg levels in hc patients increased rapidly and decreased slowly . remarkably , decreasing ranges in rc and pc were not obvious compared to other cancer types [ figure 1 , table 3 ] . therefore , it is necessary to control bg in dc patients . in diabetic patients , special attention is needed for those with hc , gc and cc at the beginning of the tpn infusion , and rc and pc patients during prolonged tpn infusion . in the nondiabetic group , attention diagnosis ( a ) , gender ( c ) , insulin ( e ) , bmi ( g ) and tpn duration ( i ) in diabetic patients . diagnosis ( b ) , gender ( d ) , insulin ( f ) , bmi ( h ) and tpn duration ( j ) in nondiabetic patients . hc : hepatic carcinoma ; cc : colon carcinoma ; dc : duodenal carcinoma ; gc : gastric carcinoma ; pc : pancreatic carcinoma ; rc : rectal carcinoma . p1 : blood glucose levels pre - tpn ; p2 : blood glucose levels within 24 h of tpn ( within 24 h ) ; p3 : blood glucose levels after during tpn infusion after 24 h ( after 24 h ) . p value and corresponding f value in figure 1 tpn constituents : medium and long chain fat emulsion ( 20% , 500 ml ) ; compound amino - acids ( 8.5% , 400 ml ) , decavitamin ( 10 ml , vitamin a : 2500 iu , vitamin d2 : 200 iu , vitamin e : 15 mg , vitamin k : 2 ml ) ; micronutrient ( 10 ml , chromium chloride : 53.3 g , copper chloride : 3.4 mg , ferric chloride : 5.4 mg , manganese chloride : 0.99 mg , sodium molybdate : 48.5 g , zinc chloride : 13.6 mg , sodium fluoride : 2.1 mg ) ; concentrated sodium chloride ( 10% , ca 40 ml ) ; potassium chloride ( 3.0 g , 30 ml ) ; sodium glycero - phosphate ( 10 ml , 2.16 g ) ; glucose injection ( 50% , 250 ml ) ; insulin ( ca 30 iu ) ; glucose injection ( 10% , 1000 ml ) ; glucose and sodium chloride injection ( 500 ml : 5% glucose , 0.9% sodium chloride ) . in the diabetic group , bg in female rose higher after tpn infusion while no difference occurred in the nondiabetic group . there was no bg value difference in insulin infusion and personal bmi index in the two groups . in the diabetic group , the bg increased after tpn , no difference appearing in longer usage , but the longer using tpn , the higher bg level in nondiabetic group [ figure 1 ] . blood glucose levels were affected by tumor kind and insulin ; consequently , the results in figure 1 were further analyzed in figure 2 , to discuss the two factors separately . here , we chose patients as a control group , who were confirmed as noncancer patients after surgery [ figure 2 ] . blood glucose values increases highly within 24 h and decreases after 24 h ; however , the last values are higher than those obtained pre - tpn . hc : hepatic carcinoma ; cc : colon carcinoma ; dc : duodenal carcinoma ; gc : gastric carcinoma ; pc : pancreatic carcinoma ; rc : rectal carcinoma . in diabetic patients group , though without distinct differences , bg variation had its own characteristics in kinds of tumor . in nondiabetic patients group , bg level rose distinctly after tpn infusion ( see the p value under the pictures ) ; furthermore , there was more distinct difference in different kinds of tumor without any insulin [ figure 2d ] . the influence from various tumor types was as follows : hepatic carcinoma : as shown in figure 2 , bg levels in hc patients were high , with or without insulin in the diabetic group . it was also high and showed a large variation ( increasing and decreasing range ) in the nondiabetic group ; the decline range was not the same as with other cancer types [ figure 2d . ] after 24 h. these data indicated that bg levels in hc patients were greatly influenced by tpn.colon carcinoma : its bg level changed overtly in the diabetic group [ figure 2b ] . the increasing bg range was even higher than that of hc ; however , absolute bg values were low as shown in figure 2a , and its variation high [ figure 2c ] . this suggested the necessity to control bg levels in cc with insulin in the diabetic group.rectal carcinoma : no distinct changes in the four sub - groups and absolute values were low in the subgroups . the only difference was that decreasing bg range after 24 h was not so obvious [ figure 2a ] , indicating that extra bg control is needed in this situation.duodenal carcinoma : bg levels in dc patients rose highest in four subgroups ; hence , it is necessary to strengthen bg control in dc patients , e.g. , increasing insulin dose and decreasing glucose content.gastric carcinoma : no distinct variation was observed for the four sub - groups . absolute values within 24 h were high [ figure 2a].pancreatic carcinoma : as shown in figure 2a , its increasing range was as high as that of hc : similar features were obtained as in figure 2c and 2d.other factors : hypertension , family cancer history , tobacco and alcohol habits and blood types showed no overtly different effect on bg in either sub - group . hepatic carcinoma : as shown in figure 2 , bg levels in hc patients were high , with or without insulin in the diabetic group . it was also high and showed a large variation ( increasing and decreasing range ) in the nondiabetic group ; the decline range was not the same as with other cancer types [ figure 2d . ] after 24 h. these data indicated that bg levels in hc patients were greatly influenced by tpn . colon carcinoma : its bg level changed overtly in the diabetic group [ figure 2b ] . the increasing bg range was even higher than that of hc ; however , absolute bg values were low as shown in figure 2a , and its variation high [ figure 2c ] . this suggested the necessity to control bg levels in cc with insulin in the diabetic group . rectal carcinoma : no distinct changes in the four sub - groups and absolute values were low in the subgroups . the only difference was that decreasing bg range after 24 h was not so obvious [ figure 2a ] , indicating that extra bg control is needed in this situation . duodenal carcinoma : bg levels in dc patients rose highest in four subgroups ; hence , it is necessary to strengthen bg control in dc patients , e.g. , increasing insulin dose and decreasing glucose content . pancreatic carcinoma : as shown in figure 2a , its increasing range was as high as that of hc : similar features were obtained as in figure 2c and 2d . other factors : hypertension , family cancer history , tobacco and alcohol habits and blood types showed no overtly different effect on bg in either sub - group . both observational and laboratory studies have provided evidence that impaired metabolism , obesity , hyperglycemia and hyperinsulinemia may have a role in cancer development , progression and prognosis . besides , culture of breast cancer mcf-7 cells in hyperglycemia significantly promotes the motile activity in comparison to the normal physiological glucose level . diabetes may directly promote the progression of pc by pancreatic duct enlargement and hypertension , as well as enabling an increased tumor volume . hyperglycemia may be the first clinical manifestation and is helpful in the early diagnosis of pc . furthermore , antidiabetic drugs can have different effects on the occurrence and prognosis of pc . possible mechanisms for increased cancer risk in diabetes include cellular proliferative effects of hyperglycemia , hyperinsulinemia , and abnormalities in insulin / insulin - like growth factor ( igf ) receptor pathways . other potential mechanisms include increased circulating , local or bioavailable igf-1 , hyperglycemia , dyslipidemia , increased circulating or local estrogen , adipokines , and direct and indirect effects of inflammatory cytokines . the risk of developing pc can be reduced by aggressive prevention and treatment of t2 dm and obesity , and the prompt diagnosis of t3cdm may allow detection of a tumor at a potentially curable stage . hyperglycemia may have direct effects on the tumor site , or indirect effects through soluble factors . direct effects promote : ( i ) increased growth factor signaling and accelerated cell cycle . ( ii ) an initial accumulation of reactive oxygen species ( ros ) enhances mutagenesis and leads to the secondary selection of clones with diminished ros production to ensure survival . alternatively , some cancer cells also export ros to neighboring cells to ensure their own survival . ( iii ) the upregulation of chemo - attractants for invasion , such as glial cell line - derived neurotrophic factor . ( iv ) an increase in the wnt / b - catenin signaling pathway , which favors proliferation , antisenescence and invasion . indirect effects of hyperglycemia on cancer cells are mediated through ( i ) increased levels of insulin / igf-1 and/or ( ii ) inflammatory cytokines as well as ( iii ) a diminished immunological surveillance . the reduced immune response is achieved through the reduction in ascorbic acid transport in critical immune cells that diminishes their phagocytic and proliferation capabilities . both direct and indirect effects converge on cancer hallmarks ( increased proliferation , survival , invasion , and migration and accumulation of mutations in the dna ) . it is important to identify patients at risk for complications that arise from cancer treatment in the setting of preexisting diabetes . in addition , underlying hyperglycemia or hidden diabetes in a patient undergoing cancer treatment such as chemotherapy , including steroid administration , and tpn should be identified and managed . when tpn is used , bg levels should be kept under 150 mg / dl ( 8.33 mmol / l ) by pertinently administering insulin or limiting glycemic intake . moreover , bmi , and hypertension , among other factors , do not influence bg levels in a statistically significant manner . in summary , our study reveals the relationship between bg values and different tumors types with tpn in three stages ( pre - tpn , within 24 h and 210 days after 24 h ) . our findings indicate the necessity to separate patients by tumor types and control bg levels in the correct setting , besides taking into account the diabetic and nondiabetic condition . special bg control is needed for dc , hc and cc patients , in both the diabetic and nondiabetic groups .
background : hyperglycemia is associated with poor clinical outcomes and mortality in several patients . however , studies evaluating hyperglycemia variation in tumor patients receiving total parenteral nutrition ( tpn ) are scarce . the aim of this study was to assess the relationship between glycemia and tumor kinds with tpn by monitoring glycemic variation in tumor patients.methods:this retrospective clinical trial selected 312 patients with various cancer types , whose unique nutrition treatment was tpn during the monitoring period . all patients had blood glucose ( bg ) values assessed at least six times daily during the tpn infusion . the glycemic variation before and after tpn was set as the indicator to evaluate the factors influencing bg.results:the clinical trial lasted 7.5 3.0 days adjusted for age , gender , family cancer history and blood types . there were six cancer types : hepatic carcinoma ( hc , 21.8% ) , rectal carcinoma ( 17.3% ) , colon carcinoma ( cc , 14.7% ) , gastric carcinoma ( 29.8% ) , pancreatic carcinoma ( 11.5% ) , and duodenal carcinoma ( dc , 4.8% ) . the patients were divided into diabetes and nondiabetes groups . no statistical differences in tpn glucose content between diabetes and nondiabetes groups were found ; however , the tumor types affected by bg values were obvious . with increasing bg values , dc , hc and cc were more represented than other tumor types in this sequence in diabetic individuals , as well as in the nondiabetic group . bg was inclined to be more easily influenced in the nondiabetes group . other factors did not impact bg values , including gender , body mass index , and tpn infusion duration time.conclusions:when tumor patients are treated with tpn , bg levels should be monitored according to different types of tumors , besides differentiating diabetes or nondiabetes patients . special bg control is needed for dc , hc and cc in both diabetic and nondiabetic patients . if bg overtly increases , positive measurements are needed to control bg values . the clinicaltrials.gov i d is nct02024321 .
SECTION 1. SHORT TITLE; TABLE OF CONTENTS. (a) Short Title.--This Act may be cited as the ``Open and Accountable Campaign Financing Act of 2001''. (b) Table of Contents.--The table of contents of this Act is as follows: Sec. 1. Short title; table of contents. TITLE I--DISCLOSURE Sec. 101. Additional monthly and quarterly disclosure reports. Sec. 102. Reporting by national political party committees. Sec. 103. Increased electronic disclosure. Sec. 104. Public access to broadcasting records. TITLE II--SOFT MONEY OF NATIONAL POLITICAL PARTIES AND CONTRIBUTION LIMITS Sec. 201. Limit on soft money of national political party committees. Sec. 202. Judicial review. Sec. 203. Increase in contribution limits. TITLE III--MISCELLANEOUS PROVISIONS Sec. 301. Prohibition of solicitation of political party soft money in Federal buildings. Sec. 302. Update of penalty amounts. Sec. 303. Activities of membership organizations and their affiliates. Sec. 304. Filing of Senate reports with the Federal Election Commission. TITLE I--DISCLOSURE SEC. 101. ADDITIONAL MONTHLY AND QUARTERLY DISCLOSURE REPORTS. (a) Principal Campaign Committees.-- (1) Monthly reports.--Section 304(a)(2)(A) of the Federal Election Campaign Act of 1971 (2 U.S.C. 434(a)(2)(A)) is amended by striking clause (iii) and inserting the following: ``(iii) additional monthly reports, which shall be filed not later than the 20th day after the last day of the month and shall be complete as of the last day of the month, except that monthly reports shall not be required under this clause in November and December and a year end report shall be filed not later than January 31 of the following calendar year.''. (2) Quarterly reports.--Section 304(a)(2)(B) of such Act is amended by striking ``the following reports'' and all that follows through the period and inserting ``the treasurer shall file quarterly reports, which shall be filed not later than the 15th day after the last day of each calendar quarter, and which shall be complete as of the last day of each calendar quarter, except that the report for the quarter ending December 31 shall be filed not later than January 31 of the following calendar year.''. (b) National Committee of a Political Party.--Section 304(a)(4) of the Federal Election Campaign Act of 1971 (2 U.S.C. 434(a)(4)) is amended by adding at the end the following flush sentence: ``Notwithstanding the preceding sentence, a national committee of a political party shall file the reports required under subparagraph (B).''. (c) Conforming Amendments.-- (1) Section 304.--Section 304(a) of the Federal Election Campaign Act of 1971 (2 U.S.C. 434(a)) is amended-- (A) in paragraph (3)(A)(ii), by striking ``quarterly reports'' and inserting ``monthly reports''; and (B) in paragraph (8), by striking ``quarterly report under paragraph (2)(A)(iii) or paragraph (4)(A)(i)'' and inserting ``monthly report under paragraph (2)(A)(iii) or paragraph (4)(A)''. (2) Section 309.--Section 309(b) of the Federal Election Campaign Act of 1971 (2 U.S.C. 437g(b)) is amended by striking ``calendar quarter'' and inserting ``month''. SEC. 102. REPORTING BY NATIONAL POLITICAL PARTY COMMITTEES. Section 304 of the Federal Election Campaign Act of 1971 (2 U.S.C. 434) is amended by adding at the end the following: ``(e) Political Committees.-- ``(1) National and congressional political committees.--The national committee of a political party, any national congressional campaign committee of a political party, and any subordinate committee of either, shall report all receipts and disbursements during the reporting period. ``(2) Itemization.--If a political committee has receipts or disbursements to which this subsection applies from any person aggregating in excess of $200 for any calendar year, the political committee shall separately itemize its reporting for such person in the same manner as required in paragraphs (3)(A), (5), and (6) of subsection (b). ``(3) Reporting periods.--Reports required to be filed under this subsection shall be filed for the same time periods required for political committees under subsection (a)(4)(B).''. SEC. 103. INCREASED ELECTRONIC DISCLOSURE. Section 304 of the Federal Election Campaign Act of 1971 (2 U.S.C. 434), as amended by section 102, is amended by adding at the end the following: ``(f) Internet Availability.--The Commission shall make the information contained in the reports submitted under this section available on the Internet and publicly available at the offices of the Commission as soon as practicable (but in no case later than 24 hours) after the information is received by the Commission.''. SEC. 104. PUBLIC ACCESS TO BROADCASTING RECORDS. Section 315 of the Communications Act of 1934 (47 U.S.C. 315) is amended by redesignating subsections (c) and (d) as subsections (d) and (e), respectively, and inserting after subsection (b) the following: ``(c) Political Record.-- ``(1) In general.--A licensee shall maintain, and make available for public inspection, a complete record of a request to purchase broadcast time that-- ``(A) is made by or on behalf of a legally qualified candidate for public office; or ``(B) communicates a message relating to any political matter of national importance, including-- ``(i) a legally qualified candidate; ``(ii) any election to Federal office; or ``(iii) a national legislative issue of public importance. ``(2) Contents of record.--A record maintained under paragraph (1) shall contain information regarding-- ``(A) whether the request to purchase broadcast time is accepted or rejected by the licensee; ``(B) the rate charged for the broadcast time; ``(C) the date and time on which the communication is aired; ``(D) the class of time that is purchased; ``(E) the name of the candidate to which the communication refers and the office to which the candidate is seeking election, the election to which the communication refers, or the issue to which the communication refers (as applicable); ``(F) in the case of a request made by, or on behalf of, a candidate, the name of the candidate, the authorized committee of the candidate, and the treasurer of such committee; and ``(G) in the case of any other request, the name of the person purchasing the time, the name, address, and phone number of a contact person for such person, and a list of the chief executive officers or members of the executive committee or of the board of directors of such person. ``(3) Time to maintain file.--The information required under this subsection shall be placed in a political file as soon as possible and shall be retained by the licensee for a period of not less than 2 years.''. TITLE II--SOFT MONEY OF NATIONAL POLITICAL PARTIES AND CONTRIBUTION LIMITS SEC. 201. LIMIT ON SOFT MONEY OF NATIONAL POLITICAL PARTY COMMITTEES. Title III of the Federal Election Campaign Act of 1971 (2 U.S.C. 431 et seq.) is amended by adding at the end the following: ``SEC. 323. LIMIT ON SOFT MONEY OF NATIONAL POLITICAL PARTY COMMITTEES. ``(a) Limitation.--A national committee of a political party, a congressional campaign committee of a national party, or an entity directly or indirectly established, financed, maintained, or controlled by such committee shall not accept a donation, gift, or transfer of funds of any kind (not including transfers from other committees of the political party or contributions), during a calendar year, from a person (including a person directly or indirectly established, financed, maintained, or controlled by such person) in an aggregate amount in excess of $90,000. ``(b) Aggregate Limit on Donor.--No person may make an aggregate amount of disbursements to committees or entities described in subsection (a) (other than transfers from other committees of political parties or contributions) in excess of $90,000 in any calendar year. ``(c) Index of Amount.--In the case of any calendar year after 2001-- ``(1) the amounts described in subsections (a) and (b) shall be increased based on the increase in the price index determined under section 315(c), except that the base period shall be calendar year 2001; and ``(2) each amount so increased shall be the amount in effect for the calendar year.''. SEC. 202. JUDICIAL REVIEW. (a) Expedited Review.--Any Member of Congress, candidate, national committee of a political party, or any person adversely affected by section 323 of the Federal Election Campaign Act of 1971, as added by section 201, may bring an action, in the United States District Court for the District of Columbia, for declaratory judgment and injunctive relief on the ground that such section 323 violates the Constitution. (b) Appeal to Supreme Court.--Notwithstanding any other provision of law, any order of the United States District Court for the District of Columbia granting or denying an injunction regarding, or finally disposing of, an action brought under subsection (a) shall be reviewable by appeal directly to the Supreme Court of the United States. Any such appeal shall be taken by a notice of appeal filed within 10 calendar days after such order is entered; and the jurisdictional statement shall be filed within 30 calendar days after such order is entered. (c) Expedited Consideration.--It shall be the duty of the District Court for the District of Columbia and the Supreme Court of the United States to advance on the docket and to expedite to the greatest possible extent the disposition of any matter brought under subsection (a). (d) Enforceability.--The enforcement of any provision of section 323 of the Federal Election Campaign Act of 1971, as added by section 201, shall be stayed, and such section 323 shall not be effective, for the period-- (1) beginning on the date of the filing of an action under subsection (a); and (2) ending on the date of the final disposition of such action on its merits by the Supreme Court of the United States. (e) Applicability.--This section shall apply only with respect to any action filed under subsection (a) not later than 30 days after the effective date of this Act. SEC. 203. INCREASE IN CONTRIBUTION LIMITS. (a) Increase in Individual and Political Committee Contribution Limits.--Section 315(a) of the Federal Election Campaign Act of 1971 (2 U.S.C. 441a(a)) is amended-- (1) in paragraph (1)-- (A) in subparagraph (A), by striking ``$1,000'' and inserting ``$3,000''; (B) in subparagraph (B), by striking ``$20,000'' and inserting ``$60,000''; and (C) in subparagraph (C), by striking ``$5,000'' and inserting ``$15,000''; and (2) in paragraph (3)-- (A) by striking ``$25,000'' and inserting ``$75,000''; and (B) by striking the second sentence. (b) Increase in Multicandidate Limits.--Section 315(a)(2) of the Federal Election Campaign Act of 1971 (2 U.S.C. 441a(a)(2)) is amended-- (1) in subparagraph (A)-- (A) by striking ``$5,000'' and inserting ``$7,500''; and (B) by inserting ``except as provided in subparagraph (D),'' before ``to any candidate''; (2) in subparagraph (B)-- (A) by striking ``$15,000'' and inserting ``$30,000''; and (B) by striking ``or'' at the end; (3) in subparagraph (C), by striking ``$5,000.'' and inserting ``$7,500; or''; and (4) by adding at the end the following: ``(D) in the case of a national committee of a political party, to any candidate and his authorized political committees with respect to any election for Federal office which, in the aggregate, exceed $15,000.''. (c) Indexing.--Section 315(c) of the Federal Election Campaign Act of 1971 (2 U.S.C. 441a(c)) is amended-- (1) in paragraph (1)-- (A) by striking the second and third sentences; (B) by inserting ``(A)'' before ``At the beginning''; and (C) by adding at the end the following: ``(B) Except as provided in subparagraph (C), in any calendar year after 2002-- ``(i) a limitation established by subsection (a), (b), (d), or (h) shall be increased by the percent difference determined under subparagraph (A); and ``(ii) each amount so increased shall remain in effect for the calendar year. ``(C) In the case of limitations under subsection (a), each amount increased under subparagraph (B) shall remain in effect for the 2-year period beginning on the first day following the date of the last general election in the year preceding the year in which the amount is increased and ending on the date of the next general election.''; and (2) in paragraph (2)(B), by striking ``means the calendar year 1974'' and inserting ``means-- ``(i) for purposes of subsections (b) and (d), calendar year 1974; and ``(ii) for purposes of subsections (a) and (h), calendar year 2001''. (d) Increase in Senate Candidate Contribution Limits for National Party Committees and Senatorial Campaign Committees.--Section 315(h) of the Federal Election Campaign Act of 1971 (2 U.S.C. 441a(h)) is amended by striking ``$17,500'' and inserting ``$90,000''. (e) Effective Dates.-- (1) Except as provided in paragraph (2), the amendments made by this section shall apply to calendar years beginning after December 31, 2001. (2) The amendments made by subsection (c) shall apply to calendar years after December 31, 2002. TITLE III--MISCELLANEOUS PROVISIONS SEC. 301. PROHIBITION OF SOLICITATION OF POLITICAL PARTY SOFT MONEY IN FEDERAL BUILDINGS. (a) In General.--Section 607 of title 18, United States Code, is amended-- (1) in subsection (a), by striking ``within the meaning of section 301(8) of the Federal Election Campaign Act of 1971''; and (2) by adding at the end the following: ``(c) Definition of Contribution.--In this section, the term `contribution' means a gift, subscription, loan, advance, or deposit of money or anything of value made by any person in connection with-- ``(1) any election or elections for Federal office; ``(2) any political committee (as defined in section 301 of the Federal Election Campaign Act of 1971); or ``(3) any State, district, or local committee of a political party.''. (b) Amendment of Title 18 To Include Prohibition of Donations.-- Section 602(a)(4) of title 18, United States Code, is amended by striking ``within the meaning of section 301(8) of the Federal Election Campaign Act of 1971'' and inserting ``(as defined in section 607(c))''. SEC. 302. UPDATE OF PENALTY AMOUNTS. Section 309 of the Federal Election Campaign Act of 1971 (2 U.S.C. 437g) is amended by adding at the end the following: ``(e) Adjustment of Dollar Amounts for Inflation.--In the case of any calendar year after 2001-- ``(1) each amount specified under subsection (a) or the second sentence of subsection (d)(1)(A) shall be increased based on the increase in the price index determined under section 315(c), except that the base period shall be calendar year 2001; and ``(2) each amount so increased shall be the amount in effect for the calendar year.''. SEC. 303. ACTIVITIES OF MEMBERSHIP ORGANIZATIONS AND THEIR AFFILIATES. (a) Permitting Corporate Members of Trade Association to Approve Solicitations by More Than One Trade Association.--Section 316(b)(4)(D) of the Federal Election Campaign Act of 1971 (2 U.S.C. 441b(b)(4)(D)) is amended by striking ``, and such member corporation'' and all that follows and inserting a period. (b) Treatment of Certain Employees and Others as Executive and Administrative Personnel.--Section 316(b)(7) of such Act (2 U.S.C. 441b(b)(7)) is amended by striking ``responsibilities.'' and inserting the following: ``responsibilities (without regard to whether the individual is a member or affiliate of a labor organization), and includes salaried foremen or others having direct supervision over employees paid on an hourly basis, and any individuals with professional responsibilities who are paid by the corporation as consultants or independent contractors (without regard to whether such individuals are classified as employees of the corporation for any other purpose).''. SEC. 304. FILING OF SENATE REPORTS WITH THE FEDERAL ELECTION COMMISSION. (a) Section 302 Amendment.--Section 302 of the Federal Election Campaign Act of 1971 (2 U.S.C. 432) is amended by striking subsection (g) and inserting the following: ``(g) Place of Filing.--All designations, statements, and reports required to be filed under this Act shall be filed with the Commission.''. (b) Conforming Amendments.--Title III of the Federal Election Campaign Act of 1971 (2 U.S.C. 431 et seq.) is amended-- (1) in section 304-- (A) in subsection (a)(6)(A), by striking ``Secretary or the Commission'' through ``as appropriate'' and inserting ``Commission and Secretary of State'', (B) in the third sentence of subsection (c)(2), by striking ``the Secretary or'', and (C) in the fourth sentence of subsection (c)(2), by striking ``the Secretary, the Commission,'' and inserting ``the Commission''; and (2) in section 311(a)(4), by striking ``Secretary or the''.
Open and Accountable Campaign Financing Act of 2001 - Amends the Federal Election Campaign Act of 1971 (FECA) to revise reporting requirements, including: (1) changing from quarterly to monthly the additional reports required to be filed with regard to the principal campaign committee of a candidate for the House of Representatives or the Senate in any calendar year during which there is a regularly scheduled election for which such candidate is seeking nomination or election; (2) requiring a national committee of a political party to file the same monthly reports designated for all political committees other than authorized committees of a candidate; (3) requiring the national committee of a political party, any national congressional campaign committee of a political party, and any subordinate committee of either, to report all receipts and disbursements during the appropriate reporting period; and (4) directing the Federal Election Commission (FEC) to make report information available on the Internet and at FEC offices.Amends the Communications Act of 1934 to require a licensee to maintain and make available for public inspection a complete record of certain requests to purchase broadcast time that are related to legally qualified candidates.Amends FECA to: (1) limit to $90,000 aggregate (indexed for inflation) per calendar year per contributor the amount of soft money a national committee of a political party, a congressional campaign committee of a national party, or an entity directly or indirectly established, financed, maintained, or controlled by such committee may accept; (2) prohibit any person from making an aggregate amount of disbursements to such committees or entities (other than transfers from other committees of political parties or contributions) in excess of $90,000 (indexed for inflation) in any calendar year; (3) increase individual, political committee, and multicandidate political committee contribution limits; (4) revise indexing provisions; and (5) increase Senate candidate contribution limits for national party committees and senatorial campaign committees.Amends the Federal criminal code to prohibit solicitation of soft money in any room or building occupied in the discharge of official duties by an officer or employee of the United States or any department or agency thereof, or by a person receiving any salary or compensation for service from the Treasury.Amends FECA to: (1) provide for indexing of penalty amounts; (2) permit corporate members of trade associations to approve the soliciting of contributions by more than one such trade association in any calendar year; and (3) require the filing of all Senate FECA reports to be with the FEC.
the etiology is multifactorial with the factors involved being genetic , physiological , behavioral , environmental , financial and political . childhood obesity is considered by the world health organization ( who ) as a new epidemic , it has been characterized as the number one health problem worldwide and it is considered as one of the \documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{upgreek } \usepackage{mathrsfs } \setlength{\oddsidemargin}{-69pt } \begin{document } } { } $ 21^{\mathrm { st}}$ \end{document } century s most important public health challenges . according to the estimates of the who , the number of overweight or obese children will exceed 54 million in 2015 . childhood obesity can harm seriously children s health and it is a potential cause for some social and psychological problems . therefore , there is an urgent need to overcome this problem from the roots with effective prevention and treatment approaches . the american academy of pediatrics guidelines target the reduction of total and abdominal obesity through increased physical activity and healthy nutrition . although , recent research has demonstrated the efficacy of these lifestyle changes on weight loss and weight maintenance , as well as , on the prevention of comorbidities , promotion and maintenance of such changes continues to be a challenge . several systematic reviews have shown that web based interventions are moderately effective in promoting weight loss . a personalized approach and intervention , with a two way feedback , there are several behavioral interventions that have demonstrated encouraging short - term results , but they do not have consistent results as far as the long - term maintenance of weight loss . thus , research for better models that can easily be delivered and sustained overtime , is needed . to that end , mobile health development intervention could greatly benefit from the application of the health behavior theory . behavioral intervention is the less invasive solution and , more important , their effects could benefit the long term . nevertheless , the children s intelligence and psychology are immature , they are sensitive to the peer pressure and the new consciousness , so the behavioral interventions that aim at changing the child s eating and activity behavior through education and counseling , should be tailored to the specific needs and the characteristics of this target group . there are many types of behavioral interventions for childhood obesity which have positive effects in the prevention and treatment of the disease , such as family - based , school - based , community - based interventions , etc . . school - based intervention and other interventions involving professional personnel can provide children with the most appropriate support , but they hardly might be sustainable in the long - term . in contrast , almost all families always accompany children for the whole childhood , more than a teacher or a health care provider , so the family can offer to the children sustained helps and support . furthermore , children at home have more time to perform various activities and they eat more than 2 meals every day with their parents , meanwhile parents can realize one - on - one observation and a more attentive interaction with their children . it has been demonstrated that parental involvement can lead to clear benefits in the treatment of childhood obesity . the temporal flexibility , multiple opportunities , and parents one - on - one care makes the stay at home and the home environment more suitable to apply technological solutions to provide parents with the appropriate tools and professional support to improve the result of any behavioral interventions . information and communication technologies ( icts ) have been largely used within the health - care context , the combination of health - care and icts , e - health , has a great impact on the health industry . several icts systems for the education and the behavioral intervention in the family environment have been implemented for childhood obesity . serious games ( using games for a primary purpose other than pure entertainment ) and gamification techniques ( using mechanism techniques outside game context ) have been widely used and combined with social networks and monitoring technologies in order to let the children have a well - balanced meal , to know the correlation between the calories they eat and the calories they burn , and to exercise during their stay at home , . those existing game systems could result in an improvement of children s lifestyle for a limited time period , but they are not designed to be a long - term planning and scheduling system to achieve a substantial and targeted behavior modification . in the case of family - based intervention , icts could also provide guidelines to parents education , e.g. online health information is provided to parents through generalized websites or search engines ( google , wikipedia , etc . ) , but the information on these sites is usually general and complicated to be used in each particular case . two - end behavior modification systems based on family - based behavioral intervention let parents design behavioral tasks for the child , track the completion of tasks , and give incentives , and use gaming and social networks to activate children to perform tasks . more importantly , they are not intelligent systems , as they do not provide personalized behavior modification programs based on the characteristics and needs of the different children , they do not adjust the outcome based on the feedback from the completion of tasks , and they do not provide expert guidance . a family - based behavior intervention is a long and complex course of treatment , there are various factors that can influence the treatment outcome , and the intervention requires the cooperation among professionals , parents and children . hence , taking advantage of icts to resolve the difficulties met in a family - based intervention could improve its efficiency and optimize its result . the main goal of this work is to define an ict system implementing a family - based behavioral intervention for the management and treatment of childhood obesity . to achieve this , a state of the art analysis of existing solutions and technologies available to this purpose was carried out ; then , the results of this analysis were discussed with experts and a suitable model of family - based intervention of childhood obesity was derived , using the analytic hierarchy process ( ahp ) . finally , a system prototype called ob city was designed , based on the intervention model and experts advice . ob city is a technological platform that supports the management of childhood obesity by educating , helping and encouraging children to modify their behavior , and empowering their parents at the same time . the remainder of the paper is organized as follows : in section ii , the state of the art analysis , the analytic hierarchy process and the techniques to implement the system are described , as well as the materials that are used to evaluate the user need and the prototype . in section iii , the ict system is described , and the childhood obesity family care model , the ob city s solutions and prototype and the result of the user need elicitation are provided . finally , the possible optimizations , clinical applications of the system and future work are discussed in section iv . we organized our in three phases : first , existing family - based behavior interventions were analyzed , and the related existing technological solutions were selected ; secondly , a family based childhood obesity care model was defined and evaluated through the involvement of experts using the ahp ; and finally , a first prototype of the ob city system has been designed and iteratively updated with the help of user interaction experts . the phases of our work . the literature study and expert interview are performed in order to have a preliminary understanding of childhood obesity ; to understand causes and consequences of child obesity , as well as existing prevention and treatment solutions ; and to carry out an in - depth study of the working mechanism of behavioral intervention . meanwhile , a research on current technological solutions was also performed . the result of this process consists in a depth understanding of the family - based intervention of childhood obesity , a first approximation in describing the basic components of family - based interventions and a selection of the current icts solutions that can support them , in order to discuss and further elaborate it with the help of experts in the field . to define a system that can provide service for all family - based intervention dimensions , the analytic hierarchy process was chosen and used to elicit the intervention needs . on the ahp , the result of the literature study and the experts interviews were used to establish a hierarchical model of family - based interventions as a reference for the prototype design . an evaluation of the elements of the model was carried out to obtain an accurate guidance for the development of the ob city system based on the integrated views of a group of experts in the topic . ahp has been widely employed in different fields such as education and health , for complex decision making problems . ahp enables the elicitation and prioritization of users needs by aggregating the opinion of domain experts providing a quantitative measure of their opinions and level of agreement . participants are requested to perform multiple pairwise comparisons between two elements of the hierarchy instead of ranking all the elements at once . for each pairwise comparison they are asked to choose which one of the two options is more important and rank it in a 10-points scale . using this information and due to the properties of the ahp , an inconsistency value is calculated in real time and provided to the participants to reconsider their responses . once the questionnaires are finalized , it is possible to extract the relative importance of each need per category ( local weights , lw ) , the relative importance of each category ( category weights , cw ) , and the importance of each need compared to all the others ( global weights , gw ) , . for all these reasons , ahp has been selected as the method to elaborate the hierarchy model of a family - behavioral intervention , since it is a complex problem that requires expertise and know - how from various domain experts . at the beginning , the first version of the hierarchy then the hierarchy was refined and updated through the knowledge , experience , judgment , value , opinion and needs , of medical , educational and engineering experts . finally , the hierarchy was ranked by other experts , in order to assist the development and evaluation tests : two nutritionists with more than 15 years of clinical experience and one primary school teacher with more than 20 years experience have been interviewed ; the final hierarchy was evaluated by 2 nutritionists , 1 endocrinologist , 3 primary school teachers and 3 biomedical engineers with experience in childhood obesity . another method employed within our work was the use early prototyping as a way to start a dialogue with experts and obtain their feedback . the prototype was designed according to the elements of the hierarchy and then it was shown and discussed with various experts . one nutritionist with more than 20 years experience together with two bio - engineers with 2 years experience tested the prototype display against the elements of the model to evaluate the system s functionality , and determine if the system was able to provide support for every important dimension of the treatment and if it can be accepted by both parents and children . with these evaluations , rapid iterators over a prototype yields valuable design insights for both the experienced and non - experienced participants and it is a valuable tool for promoting the dialogue with experts and capture their feedback . axure rp pro is an application designed for rapid prototyping , it can assist the designer to quickly design the prototype , combined with comments , notes , flow charts , frames and other elements and to obtain a complete product presentation . it is a tool that can construct highly immersive website and app prototypes and generate an interactive display specifications document . employing the outcome of the ahp , the care model of family - based intervention , the ob city s system framework and function modules are designed and visualized through axure and the prototype is presented to the experts , to evaluate it and to achieve continuous improvement . bpmsg ahp online system is a free web system developed based on the analytic hierarchy process , and it can be used to support rational decision making . users can define a hierarchy of criteria for a decision problem , calculate the priorities and evaluate a set of decision alternatives against those criteria . when the hierarchical model of family - based intervention is defined in the ahp step , we upload the objective and relevant criteria and structure them in a hierarchy in the bpmsg ahp online system . then the experts are invited to realize a comparison of those criteria with respect to the objective of optimize the effect of the family - based intervention to find their weights based on pairwise comparisons . the result of the needs analysis of different experts is evaluated and is directly exported without any additional operation on the website . using our state of the art analysis several insights for the definition of a family - based behavior intervention are extracted . first of all , it is an event that occurs in the family environment , so the active participation of children and parents is necessary and essential . second , the intervention for obesity focuses on two targets : letting children be healthy by eating less and doing more physical activity , consequently , the service needs to include nutrition and exercise components . third , the behavior interventions are implemented through three pillars : education , counseling and motivation . forth , the intervention requires an accurate analysis of the individual and a modification plan has to be defined for each case , in order to obtain the desired objective . and finally , the result of the behavior intervention should be maintained for a long time , therefore children can keep a long - term healthy without rebound . in conclusion , 9 dimensions of family - based intervention were defined as follows : provide personalized nutrition and exercise services to educate , consult and encourage both children and parents to obtain long - term effects of the childhood obesity treatment . at the beginning , existing icts products employed in the family - based intervention have been described and some simple evaluations have been presented . in this part a detailed analysis of the state of the art of the family - based intervention technological solution and its advantages and disadvantages are provided . these technologies have been evaluated , as described in table 1 , based on the 9 criteria defined at the beginning of this section.table 1comparison of existing applicationscriteriaapplicationpick chow!fitter crittersyour snacktrainergooglebehavioral changechild end\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } \usepackage{amsfonts } \usepackage{amssymb } \usepackage{amsbsy } \usepackage{upgreek } \usepackage{mathrsfs } \setlength{\oddsidemargin}{-69pt } \begin{document } } { } $ \checkmark$ \end{document}\documentclass[12pt]{minimal } \usepackage{amsmath } \usepackage{wasysym } 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, which are compared in table 1 , most of these systems provide services only for the children end , while two require the participation of parents . children need to modify their diet and exercise habit in the intervention , which can be achieved through a similar pattern of behavior modification , but only 2 of them provide services in both areas . education , consultation and encouragement are complementary to achieve the purpose of behavior changing , but just 1 of the systems has all those function . the concept of long term intervention effect is applied in 3 systems , but they are non - flexible , and there is not a gradual , evidence - based and scientific - grounded process . none of them provides personalized behavior modification programs based on the characteristics and state of the family members . in order to define an ict system to overcome the weaknesses of the existing technology products , the 9 criteria obtained in the state of the art analysis have been further elaborated by experts . according to the medical experts opinion , emotion was added as the 10th criterion to the model because it affects childhood s weight as same as nutrition and exercise , and these three elements can interact with each other . finally , the experts reorganized the 10 criteria and grouped them in three new categories : 1 ) parents have a healthy lifestyle , and they become good examples to affect their children s behavior ; 2 ) parents know ways of behavior modification and make use of scientific methods to modify children s behavior ; 3 ) children are motivated to actively participate in the intervention . children imitate almost everything that their parents do and integrate what they observe into their lives . it is important that parents become good examples for their children in the behavior intervention . parents should have and show good diet habits and exercise activities and create a healthy lifestyle environment ; they should also have stable emotion to reduce children s psychological pressure . behavior intervention is not a complicated process , but to achieve the desired goal of the intervention is not a simple task . family - based behavior intervention requires parents to know about behavior modification techniques , such as how to give to the children a reasonable modification plan , how to properly motivate children , to realize better intervention results . during the behavior modification , parents need to be very careful to observe children , to understand accurately the children s various states ( daily behavior , personality and clinical data ) , to judge the children behavior properly , and to improve the efficiency of the intervention . children are indispensable part of the family - based intervention , and they are real actors of the behavioral change , so children s performance directly affects the result of the intervention . if they do not have the motivation to participate in the process , the whole behavior modification is completely pointless . and if in the course of the intervention , children do not have the ability to control themselves , or have very bad emotional state , they will not be able to adhere to complete a series of tasks to achieve behavioral change . in addition , if the behavior modification solely let children correct some of their behavior , but they do not know the reason or they can not distinguish correct or wrong behavior , it is not good for the children to establish a good behavior independently . so children have to participate actively in the behavior modification , adhere and place effort to change their behavior , and learn at the same time . the defined family - based intervention hierarchy model was presented to 2 nutritionists , 1 endocrinologist , 3 primary school teachers and 2 biomedical engineers to evaluate the importance of each element through the guidance of the bpmsg ahp system , the results are shown in table 2 and table 3:table 2ranking of global weights ( gw)rankingelementweights1good parents - children relationship14.9%2parents have healthy diet habits13.9%3child has good self - control and confidence12.8%4parents have balanced emotion10.4%5parents are exercising9.6%6parents know behavior modification theory9.4%7parents know children s behavior6.6%parents know children s psychological state6.6%9children engage with intervention actively6.2%10children have knowledge on healthy habits5.2%11parents know children s clinical state4.6%table 3ranking of categorical weights ( cw)rankingelementweights1parents are good examples48.7%2parents modify children s behavior27.2%3children modify their behavior24.1% based on the values from the global weights ( gw ) , the three most important elements are good parents - children relationship ( 14.9% ) , parents have healthy diet habits ( 13.9% ) and child has good self - control and confidence ( 12.8% ) . in a second level of importance there are parents have balanced emotion ( 10.4% ) , parents are exercising ( 9.6% ) , and parents know behavior modification theory ( 9.4% ) . parents know children s behavior ( 6.6% ) , parents know children s psychological state ( 6.6% ) , children engage with intervention actively ( 6.2% ) and children have knowledge on healthy habits ( 5.2% ) are en the third level , the parents know children s clinical state is the less relevant ( 4.6% ) . the analysis of the categorical weights ( cw ) provides information about the importance of the different categories . parents are good examples has been highlighted as the most relevant category by all the responders ( 48.7% ) , followed by parents modify children s behavior and the children modify their behavior which scored very similarly ( 27.2% and 24.1% ) . the results show that parents play a leading role in the family - based intervention , but children s cooperation is also indispensable , especially the child s self - control is an important element that can not be ignored . according to family - based intervention hierarchy model , an ict system called ob city is defined to provide the corresponding services to the elements in the model . as shown in figure 3 , ob city is a two - ends system involving both parents and children . users wear the sensors ( smart watch or smart bracelet ) to measure and upload some detected data ( heart rate , electro dermal activity and motion data ) to the user end to realize the emotion and exercise state , and they interact with the user end to realize some necessary behavior intervention operations . there is communication between the parents ends , between the children ends and between parents end and their child end to permit the users to interact with other users online and also off line . gamification is the use of game elements and game - design techniques in non - game contexts to solve problems and engage users , . it applies the game mechanics such as : collecting some goods , medals , etc . ; ; system feedbacks with some movements and change ; value exchange between users ; customization and personalization in the real - life or other non - game systems combines the nature of the fun of the games , to increase the users motivation and engagement . gamification techniques encourage people to achieve certain goals in non - game situations and feel the fun of the game . they are currently extensively used in health , education , , social networks and other industries , . the parent end of ob city is a health management application which integrates the gamification techniques . it allows parents to earn points to get more level and redeem more advanced services ; to perform different new challenges ; to collect some relevant award medal ; to rank in their circle of friends , compete and exchange experiences with other users in the network . it also provides the corresponding feedback to parents each operation , to maintain the parents active participation in the family - based intervention , and lets them to achieve self - management and to intervene in the children s behavior modification . a serious game is a game designed for the purpose of application , specifically speaking , refers to a game that has the main content of teaching knowledge and skills or providing professional training and simulation . serious games use the expression of game , through the interactive of edutainment , allow users gain knowledge , accept relevant information , get efficient skills training and even improve the efficacy of some medical applications . serious games have been widely used in military , medical , industrial , educational , research , training and other applications . the ob city s children end is a serious game , a virtual city is created to let children simulate real life , communicate with social network friends and take care of their virtual pets in the game . ob city requires children to complete a variety of tasks related to their behavior modification , optimization of skills and improvement of lifestyle in real life . and ob city mainly lets children form a very healthy habit and improve the obesity symptoms , and let them gain relevant knowledge , build self - confidence and establish a good personality at the same time . applied behavior analysis , also known as behavior modification , is a technique that requires a deep knowledge , research and work to achieve real change in the person s . aba s objective is to generate a change of a behavior by increasing or decreasing the frequency of certain sub - behaviors through implementing measures before ( early warning or eliminate risk ) and after ( positive and negative reinforcement ) the generation of these behaviors . aba is mostly utilized for children with an autism spectrum disorder , and it is also used in many areas such as : education , health and exercise , medical procedures , parenting , psychotherapy , etc . the ob city system provides personalized services to support the family - based intervention according to aba . it provides technical solutions for each step of the behavior modification , to help parents observe their children , find their behavior problem , formulate the behavior modification plans , take action to realize the intervention , evaluate the result and adjust plan , and motivate children to cooperate with the intervention . the purpose of affective computing is to give to the computer the ability to identify , understand , express and adapt to the human emotions , to build a harmonious human - machine environment , and give the computer a higher and more comprehensive intelligence . it uses a variety of sensors to get the physiological signal and behavioral characteristics caused by human emotions , and it establishes an emotional model , and creates a personal computing system which is able to perceive , recognize and understand the human emotion . emotion and obesity have a great relationship , they have mutual influence and constraints , . meanwhile , parents emotional state can also have a huge impact on children s emotions and behavior , . therefore , in the family - based intervention of childhood obesity , the emotional management of parents and children is a very important task . ob city combines affective computing technology , using sensors to obtain related physiological data , and combining the characteristics of the parents and children s operations in the process of using the system to give personalized feedback to help them regulate their emotions . the ob city s functional modules are defined according to the family - based intervention hierarchy model , as it is shown in table 4.table 4tecnological solutions to support the family - based intervention hierachy modelchildhood obesity family - based intervention needsob city s solution1.1 parents have healthy diet habitsit is proven that parents eating habits will directly affect their children , . if parents have a long - term heavy intake of high - carbohydrate and high - fat foods , children will be exposed to excessive intake of calories . personal dietary preferences , irregular schedule and lack of expertise make parents just buy and prepare what is their favorite , what is fast and easy to do and what they think is good for health without considering the practical nutritional value of food . to change their eating habits , they need to recognize the problems of their diet habit which may cause a series of serious health problems and have the motivation to correct them ; then , they should study nutritional facts to know what a good diet is ; finally , they try to change their diet , and stick with it.provide nutrition , exercise , and emotional management system for parentsob city provides services to permit parents manage their eating behavior , exercise behavior and emotional balance . it will let parents to improve their behaviors through education , guidance , and supervision.at the education part , ob city will periodically send professional information related to nutrition , exercise and psychology to parents , so that they can slowly learn relevant knowledge to know how to establish a healthy lifestyle independently.at the guidance part , ob city will offer directly to parent lifestyle programs personalized according to their preference to facilitate their work of behavior control . based on the parents choice of their life custom , the system will generate automatically a diet and activity plan , to let parent make the lifestyle healthier . at the same time , ob city uses affective computing techniques to detect the parents emotion with sensors ( heart rate and electrodermal activity ) , informs them the state of their emotion and gives suggestions , to let them understand better their mood and try to control it.at the supervision part , the system provides two mechanisms : self - supervision and supervision by others . first , the system uses the gamification techniques , to motivate parents to follow well the lifestyle program proposed by the system , to modify their emotion and lifestyle . it also takes advantage of the social network , let parents to supervise and compete with each other and the link between parents end and the children end permits children to supervise their parents.1.2 parents are exercisingchildren can spend a lot of leisure time at home to do more physical exercise than at school . the lack of physical activity is a frequent problem of our days , the economic growth , technological progress , and social changes have led many people to take public transport instead of walking , have sedentary jobs to carry out the work , watch tv , play video games and use the computer at home . to change this , parents must understand the benefit of physical exercise in a daily basis ; also , they need to have access to relevant ( and trustable ) knowledge sources , so that they can efficiently carry out physical exercise according to their personal state.1.3 parents with balanced emotionparents emotion in family life affects directly the children s mental health . parents often have bad mood at home , they fight and quarrel , even vent their negative emotion directly to the children , let children often live in tension and fear . children s psychological problems will affect their behavior , lose self - confidence and self - control , become easy to give up and do not take the initiative to improve themselves . parents in daily family life must control their emotions : do not quarrel or fight in front of children , do not complain about life or show decadent emotion in front of children , do not scold or criticize others in front of children , do not express their views in an extreme way in front of the children , and most important , do not scold the children directly.1.4 parents and children having good communicationthe relationship between parents and children might influence the children s whole life , and also affect the inheritance of parents good behavior . in order to establish good relation between parents and children , parents need to offer children real accompany . parents should try to find enough time to be close to the children , to play with them , chat with them and do other things with them as much as possible ; and take the initiative to express their love for children at the same time . besides that , parents should pay more attention to their children , share the anguish and joy of their children s every problem and achievement . in the exchange and communication between parent and children , parents should offer enough freedom , respect , trust and patience , so that children can grow up in a comfortable home environment.create interaction between parents and childrenob city includes the parents end and the children end and permits the mutual communication between the two ends . in this way , the system creates many opportunities for parents and children to realize online and offline interaction.online interaction : several operations in the ob city s user ends require direct or indirect interaction between children and parents . ob city sets up mechanisms for mutual supervision of children and parents , the behavior and emotion management module of parents end needs the children confirm the lifestyle and emotional state of their parents in children ends ; at the same time parents plan and intervene the behavior modification of their children through the parent s ends . ob city also sets different virtual roles for parents and children in the serious game , so that they might engage in a dialogue through their user ends to reach a mutual cooperation and encouragement in the game.offline interaction : both parents and children ends will require from parents and children to complete some offline collaborative tasks , so that parents and children can exercise , change diet and learn together in real life , thus creating opportunities for them to communicate and understand each other.2.1 parents know basics of behavior modificationbehavior modification is not a standard , step by step process , especially the behavioral intervention for childhood obesity . parents need to be able to deal with a wide variety of information , analyze it and provide feedback . parents acquire a lot of information , not only about the children s body , mind and behavioral state , but also other environmental information . some of this information is very important for behavior modification , but some is interference information or noise . parents should learn to accurately filter information in order to make the correct judgments and learn to customize the scientific program according to the children s state . at the same time they also should know appropriately adjust their intervention programs to respond to all kinds of unexpected random events during the long time intervention process.provide an intelligent applied behavior analysis system ob city provides professional support in every behavior modification step in strict compliance with the aba operation.in the ob city , parents need to enter personal information and basic behavior of their children , the system analyzes and provides some options of target behavior to let parents choose , and then generates different behavior modification programs according to parental choice . finally , parents decide a program and the system converts it into every day s tasks and delivers them to the children end . it also offers punishment or reward to encourage children to do these tasks in real life . in the intervention process , the system measures automatically children s data by sensors ( exercise and emotion data ) , and requires parents to record other children s information ( exercise and nutrition behavior ) , in such a way to provide more comprehensive observation of children without costing many parents time and energy . ob city also has an intelligent feedback system that not only shows to parents what the children have done , but also adjusts the behavior modification program automatically by learning the children s state and behavior , and provides parents with better programs . if parents are willing to become more involved in the whole process and to be more resonsible of their children s behavior modification , they can freely give veto the system s recommendation and make their own decisions.2.2 parents know children s clinical statesome children s health data , including the child s height , weight , body mass index ( bmi ) , waist - hip ratio ( whr ) and body fat are related to the childhood obesity intervention . parents need periodically to measure and record the physical data during the process , to get a better understanding of the treatment progress . meanwhile , the children s physical condition is also very important for the intervention : parents should avoid children s innutrition and anemia for the diet ; and also avoid the fatigue and injury by overdoing exercise.provide a comprehensive children monitoring systemin the whole behavior intervention process , the parents are required to record a large number of children s related data : physiological data , daily behavior , the emotional state , and some related environmental inputs.ob city creates regularly notifications to parents to alert them to record manually the children s behavior and emotion every day , and to check the child s physiological state each time . meanwhile , ob city uses a variety of methods to acquire relevant children s data directly : it is combined with various types of sensors ( smart watches , smart bracelet ) to detect the children s motor behavior ; it uses the near field communication ( nfc ) technique to create children s offline activity games and takes their motion data at the same time ; it takes advantage of the social network , let the social members detect children s eating behavior through an online game . in addition , ob city incorporates affective computing technique , through a combination of physiological data acquired by sensors , children s performance in the life simulation game and the collected information from their online dialogue , helps in analysing the children s emotion state.2.3 parents know children s behaviorparents record and observe the children s behavior throughout the entire process of behavior modification ; they collect the children s behavior in all the processes of applied behavior analysis : the preparation , design , intervention and evaluation . the parents should record it timely and accurately.2.4 parents know children s character and mental statewithout professional help , to understand children s personality and psychology is very difficult for parents , even they live together , parents can not totally know their children s preferences and thoughts . cheerful children participate actively in the intervention and have a higher degree of adaptability ; and sensitive children are susceptible to get various influences , thus affecting the modification progress . therefore , parents should know the children s psychological status , in order to determine the most suitable plan.3.1 children engage with the intervention activelythe children have to try again and again to complete similar tasks in the behavior modification , they need to do something they do not like or they are not used in performing under strict requirements . sometimes , children do not know the importance of the intervention , they can not give up their favorite food and they do not want to exercise , so they will never begin to change their accustomed behavior . and if they can not find the pleasure during the process , and just suffer to do what they do not want to do , they will drop out quickly . hence , children should have the motivation to participate , they can not start their behavior modification under pressure . meanwhile , in the long and tedious intervention , they should find the delights and have strong motivation , and it is better they can even take the initiative to complete the tasks and enjoy the process of self-improvement.provide a social serious game to motivate children to learn and participate in the intervention.ob city uses the interactive multimedia , creates a life simulation game in the children end to let children participate actively in the behavior modification to develop healthier habits , and access some obesity - related knowledge through playing games.in the children end , every child can create a self - designed avatar and keep pets in the game . children do the game tasks in the real life to modify their behavior , and gain game experience and coins , to make their avatar more powerful and wealthy in the game . to look after their pets , children need to know to modify the pets diet and exercise to let their pets be healthy and strong , and they also improve their nutrition and sport knowledge in this operation . ob city creates an important virtual character , the mayor of the city , who conveys all tasks , reward and punishment to the children . as it is a fictitious character that is extremely powerful for the children in the game , it will provide a greater sense of mission to children and let them be more active in doing tasks and get more sense of honor when they get a reward . in the ob city , some children s information can be shared , ranked and organized in the social network , children can see the others information , they can make friends , perform tasks together and compete with each other , they will be involved in the game more actively , and execute tasks aiming to develop a healthy lifestyle . with the social network , children can be more motivated and actively participate in the intervention.3.2 children have good knowledge on healthy habitsto let the children know the reasons , methods , and objectives of behavior modification is better than just let them change their behavior , so that they can modify behavior spontaneously without relying on the help of their parents or other adults . to know how to determine good or bad behavior , and know how to build a good behavior they have to learn the difference between the different eating habits , know the nature of different foods , and they have to understand the pros and cons of different exercise habits , which includes facts on nutritionand sport . children develop a habit of correcting behavior themselves , which not only can play a significant role in the behavior intervention , while it will bring several benefits for their after life , and even affect their children.3.3 children have good self - control and self - confidenceobese children usually have developed a lot of bad habits in a long period of time . these habits have been deeply integrated into their lives , sicne they can not control themselves or they can not avoid the temptation , they could show also this bad behavior again during the process of behavior modification . some obese children have different degrees of psychological problems , , they do not have confidence and have a great negative emotion ; it is easy to evade the issue when they face the difficulty , and it will lead to failure of the intervention . hence , children should have a good self - control , to be able to concentrate on the task and not to be subjected to external interference . meanwhile , they need to establish their self - confidence through a variety of methods , so that they believe they are excellent and they can solve the difficulties they face , so that they have a strong determination to achieve the intervention.establish a comfortable environmentas mentioned before , ob city uses several affective computing techniques to detect children s emotion state , to try to maintain children s psychological balance , to reduce the influence of affective factors to the childhood obesity treatment.children need to do tests before entering the ob city system , which include several psychological questions , to obtain children s initial psychological assessment . meanwhile , ob city is designed as a life simulation game , the behavior and performance ( career choices , color preferences , and dialogue ) of children s avatar in the game can be used to realize the data mining , and the result like children s personality and emotion state may be mapped to children s mental state in real life . in addition to obtaining information directly from children , ob city utilizes the parents observations and feelings , to be a reference of the detection of children s emotion . apart from adjusting the behavior modification plan according to children s state , ob city will give to others feedback . the utterance of the game will be changed depending on children s emotion , to make more effective to convey meaning . children will note the difference of the system and feel more comfortable and respected . when the ob city system is defined , the first prototype was designed based on the described functional modules , and then it is constantly compared and iteratively updated by the game experts and interaction experts to the final version . ob city was provided for children aged 9 to 12 , it has two user ends : parents end and children end . the two end users need to enter the system at least once a day to do some necessary operations . the main menu of the two ends is shown in fig.4 : figure 4.ob city parent end and child end main menu . ob city parent end and child end main menu . when parents enter the ob city s parents end the first time , they need to enter their children s basic information : age , sex , height , weight , obesity features , hobbies , character , etc there are six main modules in the parents end : diet , exercise , emotion , task , my child and notice . the module content is shown in table 5 : table 5parent end s module contentmodulecontentdietprovide professional nutrition and exercise information in two forms : general related knowledge and personalized prescription according to the real needs.exerciseemotionprovide general psychological knowledge , update parents emotion state and give suggestions.taskrequire parents to realize the basic task , behavior modification task , skills task , and gift task setting and task completion confirmation.my childprovide children s status , the task completion , the game behavior and the interaction with the friends in the child end.noticeexchange the system s message and the friends message . children need to select and personalize their avatar when they enter for the first time into the ob city . after a brief questionnaire , they can get into the world of the ob city to start a new and interesting virtual life . there are also six main modules of the children end : tasks , state , house , pet , shop and citizens . the module content is shown in table 6 : table vichild end s module contentrankingelementtasksprovide basic task , behavior modification task , skills task , and gift task to children to be realized in real life.stateshow the avatar s level , wealth , title and image , and the goods in the storeroom.houseprovide furniture in the storeroom to do the house decoration.petshow the pet s level and different properties value , and permit children to feed and exercise the pet.shopsell clothing , furniture and pet supplies to children.citizensshow social network rank and the new stars rank permits children to make friends and communicate with them in the game . all these modules in the parent end and child end contains the application of the technologies mentioned in the definition of ob city system , and collaborate to provide a variety of support for family - based interventions . the prototype has been modified several times to improve the user experience and optimize the service quality . as mentioned , the task module of the parent end permits parents to set tasks and to assign them to the children in their end . first , parents can not choose difficult tasks to avoid placing too much pressure to children . but when their children have completed well these tasks , parents can increase the tasks difficulty . as it is shown in fig . the behavior modification tasks permits parents to modify the task content according to children s performance . first , the system provides to the parents directly the modified choices , so that the parents just need to select the one they think is the most suitable . with the suggestion of the education professionals this interface is modified to provide to parents more references , so that they can understand the basis for the adjustment of the tasks and can have more material for the decision . in the pet module , children can choose one pet , such as a dog , a cat , a rabbit , or even a dragon and feed and exercise their pets . they need to choose the food that he has bought from the shop to feed the pet to increase its corresponding properties in the pet feed interface . as it is shown in fig . first , the evaluation criteria of food are set according to the traditional way : calories , carbohydrates , fat , protein , and fiber are chosen as the measure . then , under the guidance of game experts , these terms are changed into : energy , power , strength , speed and intelligence , the value of these items also can be changed depending on the feeding , and at the same time they can be used in other pet modules such as pet training and pet battle . this change makes the education function more interesting for children and the knowledge is gained more intuitively . in a state of the art analysis on children obesity was carried out , supported by domain experts . as a result a hierarchy of user needs was conformed and used to assess the available technological solutions for the family - based intervention for childhood obesity . after that , the ahp method was used with experts to quantify the importance of each of the user needs in the hierarchy . this was also helpful to guide the dialogue with the domain experts and to get their views and feedback . the model was discussed with domain experts as well as experienced users in order to redesign and redefine it . the most relevant results of this work are summarized in table 2 and table 4 . there , the user needs have been identified , guided by the experts opinions and then they have been quantified . those needs can be used as a guideline not only in the developing process but also in the evaluation stage to judge the function implementation of ob city . then , table 4 offers a direct mapping between users needs and gammification , serious games , applied behavior analysis and affective computing tools developed using ict . in a later work , the ob city prototype will be deployed and validated on real users . the aim of this validation will focus on ( 1 ) studying the feasibility of ict for the delivery of this kind of intervention , and ( 2 ) studying the effectiveness of the intervention itself . ob city will is suitable not only for the overweight children , but also for the normal children , and even the changes in weight and behavior of those children might be recorded . the ob city is an application of the behavior intervention , so it can also be implemented in other cases of childhood diseases , such the autistic children or for children suffering from diabetes . it can even be used to help the normal children to develop good habits , build and establish a good personal quality and develop their hobbies and skills . management of childhood obesity is a complex issue that requires time commitment from a multidisciplinary team of health professionals and from the family . given the cost and time constraints of the health systems worldwide as well as the time limitations the parents have and their inability to accompany their children , due to job time constraints , to clinic appointments , the need for a tool that can provide guidance to parents and their overweight or obese children is of outmost importance in addressing the obesity epidemic . in a clinic visit the aspects that are most frequently addressed are ( 1 ) behavioral motivation of the parents and the children in order to implement the changes suggested in their daily routine , daily physical activity and daily nutritional habits ; ( 2 ) education of the parents regarding the principles of healthy nutrition practices , related to the number of meals , the variety of nutrients and food groups that have to be included in an age appropriate nutrition program and the age appropriate physical activity , duration , intensity and frequency , and ( 3 ) education of the children , regarding healthy nutrition , a task which is very crucial for children older than 10 years old and adolescents that make independent choices regarding snacks and sometimes lunch if they are engaged in afterschool activities . knowledge is very important but is not adequate to ensure that a change in practice will follow . it is advised that the obese child is followed by a group of health professionals including the pediatrician or pediatric endocrinologist , the nutritionist , the psychologist , the physical therapist . furthermore , besides the issues addressed in the clinic with the specialists , in everyday life , children and parents face challenges and they have to adjust their food intake accordingly , and often they are overwhelmed and they do nt know how to make the appropriate changes . the ob - city is designed in such a way to address the tasks mentioned above in a continuous manner , from a distance , so that the parents are not obliged to abstain from their work and children to miss school hours . furthermore , parents and children can have guidance and answers regarding questions which arise on a daily basis . it is the tool that can augment the compliance of parents and children and thus improve the clinical outcome . the major issue for failure of most of the plans for obese children is noncompliance . the interactive parents and children platform is unique in the aspect that sets limits to parents and do nt allow them to be unrealistic regarding their expectations for their children . the parents are given the rationale for the choices so they become aware of the reasoning as well as the needs , preferences and capacities of their children . another very important aspect by which the use of ob city can increase adherence to the suggestions and improve clinical outcome is that it takes into account the emotional status of parents and the children , as well as the ability of psychological control of children and whether parents are aware of their child emotional state . the use of sensors by which the motor activity and emotion state can be recorded provides input of the daily alterations , which are taken into account for further suggestions and modifications of the management plan . the above features ensure that ob - city can be a significant tool to support clinicians not only for the management of overweight and obese children but also for normal weight children who were documented to have rapid weight gain and for children with other clinical conditions that need behavioral modification .
childhood obesity is becoming one of the 21st century s most important public health problems . nowadays , the main treatment of childhood obesity is behavior intervention that aims at improve children s lifestyle to arrest the disease . information and communication technologies ( icts ) have not been widely employed in this intervention , and most of existing icts systems are not having a long - term effect . the purpose of this paper is to define a system to support family - based intervention through a state - of - the - art analysis of family - based interventions and related technological solutions first , and then using the analytic hierarchy process to derive a childhood obesity family - based behavior intervention model , and finally to provide a prototype of a system called ob city . the system makes use of applied behavior analysis , affective computing technologies , as well as serious game and gamification techniques , to offer long term services in all care dimensions of the family - based behavioral intervention aiming to provide positive effects to the treatment of childhood obesity .
we know that the onset of drug addictions is determined by a complex combination of constitutional ( biological ) , social , and psychological factors . physiological components play a crucial role in the maintenance of psychological anxiety , associated with physical abstinence , but they are not the one and only etiological factor behind this disorder and they can not entirely explain the motivation for subsequent relapses . it is clear that every psychoactive drug induces a specific state of intoxication , but individual psychopathology largely defines the subject 's reaction towards the pharmacological effects . bearing in mind these assumptions , we review a series of developments in the understanding of substance abuse starting with classical psychodynamic approaches based on drive / conflict models . then , we present comprehensive theories of affect regulation which we see as a starting point for the transition to modern mentalization - based conceptualizations . we describe the shift from the initial emphasis on instinctual gratification to the investigation of ego development and pathology . we show how contemporary psychodynamic clinicians and researchers can increasingly rely on mentalization based theories to explain personality pathology . there is clear evidence supporting neurobiological and neurocognitive adaptations to specific drug exposure , the natural history of addiction involving spontaneous recovery with minimal intervention , consideration of now copious evidence from other therapeutic interventions such as motivational interviewing that appear to also emphasize the interpersonal environment in treatment . our main aim is to examine the evolution of psychodynamic approaches to addictions which we see as parallel to the general development in psychodynamic clinical theories . abraham tried to conceptualize this form of pathology from the point of view of the libidinal theory , that is , as a symptom of regress to oral fixations and striving for orgasmic experiences . rad was the first to point out that not the toxic agent itself , but the impulse to use it , defines addictions . in general these authors understood substance abuse from the point of view of euphoric - pleasurable experiences and believed that the symptom has a glover , however , made an important breakthrough with his hypothesis that the psychoactive substance could be used progressively not only for regressive satisfaction , but also for protecting the subject from primitive ( destructive and self - destructive ) impulses or even psychosis . these ideas would later serve as a basis for khantzian 's work on the self - medication hypothesis . the main difference between ego - psychological theories and classical - drive / conflict models is that ego psychologists shift the focus from the symptom to the personality deficits of addicts and their incapability for coping with traumatizing anxiety . drug use is related to specific ego pathology manifested in quick shifts from depressive states to intensive arousal in conflictual relations with important others . addicts react to situations of crisis with affect regression ( totalization of feelings ) , which is dealt with by splitting unacceptable parts of internal or external reality and denying their existence . however , only when these series of operations are pharmacologically reinforced , a sense of mastery and raised self - esteem can be restored . this generation of psychodynamically oriented clinicians concentrates on the clinical reality that patients with drug addiction complain of being either overwhelmed by intolerably painful affects or cut off from their emotions . referring to these characteristics of the affective life of addicts , wieder and kaplan the problem with drug addicts is that the primitive defense mechanisms they employ do not efficiently protect them from excessive anxious and depressive states . consequently , addicts present not only interpersonal difficulties , affect storms , and impulsive behavior , typical for patients with borderline personality disorder , but their whole emotional life is in a way much more easily thus , impaired affect regulation comes into focus as a central diagnostic feature of this disorder . this term denotes a qualitative transformation of affective states with modification of their intensity and/or duration . it encompasses an interaction between neuro - physiological , motor - expressive , and cognitive - experiential areas . constant defensive blocking of affectivity leads to a state in which emotions are treated as physiological attacks setting vicious circles such as i am afraid to be afraid . we can safely generalize that the contemporary psychodynamic approach to drug addictions abandoned altogether early conceptualization of pleasure seeking and symbolic importance of the drug . instead , leading authors like khantzian see the motivation behind substance use as an attempt for self - medication . he observes that patients addicted to opiates rely on the antiaggressive effects of the substance which block disorganizing and threatening affective states of anger , pain , shame , and loneliness . khantzian convincingly shows that regressive aspects of the psychopharmacological effect have been excessively stressed , leading to a neglect of its progressive functions , that is , blockage of primitive psychic states and reinforcement of ego defenses drug addicts do not just search for an krystal points that only when the small child is protected from exposure to continuous trauma in early relations , it can develop affect tolerance during latency and adolescence . he makes it clear that primary self - regulation deficits in drug addicts encompass a tendency for affective regress , deficient capability for using anxiety as a signal , and impaired tolerance for painful emotions , especially the primitive affect of undifferentiated anxiety and depression . these deficiencies showing failure in the desomatization , verbalization , and symbolization of affective experiences are quite often observable in psychosomatic conditions characterized by the state of alexithymia . addicted patients often share some of the following basic components of alexithymic functioning : ( 1 ) difficulty in identification and differentiation of feelings and bodily senses in a state of emotional arousal , ( 2 ) difficulty in describing feelings , ( 3 ) limited imagination and poor fantasy life , and ( 4 ) cognitive style focused on external reality . without having a good enough understanding of their mental states , these patients can not modulate emotions and instead show tendencies for direct discharge of anxiety in behavior or somatizations . interpersonal disappointments easily trigger rapid changes in mood , which an individual with certain predispositions would try to regulate by pharmacological means . a concept highly applicable to addictions , is also one of the roots of contemporary mentalization - based theories . the concept of mentalization was introduced by pierre marty in the 70s as an extension of the research into psychosomatic phenomena . classically it refers to the quality and quantity of psychic representations , their verbalization , and connections with affectivity . from another point of view that of modern developmental psychopathology fonagy [ 15 , p. 4 ] defines mentalization as a form of mostly preconscious imaginative mental activity , namely , interpreting human behavior in terms of intentional mental states ( i.e. , needs , desires , feelings , beliefs , goals , purposes , and reasons ) . this conceptualization integrates the notion of theory of mind in cognitive developmental models with attachment theory . it is based on the following three main assumptions : ( 1 ) the feeling of the self as agent is rooted in the experience of being attributed psychic states by a significant other , ( 2 ) this capability is a function of the interaction between the caring figures through a process of mirroring , ( 3 ) its development can be impaired by traumatic experiences . attachment is seen as the main factor in the development of mentalization and the formation of internal representations of affective states . secure attachment is a precondition for good enough affect regulation and guides the transition from coregulation in the mother - infant couple towards self - regulation of the child . the child internalizes mother 's empathic expression and this type of intersubjectivity is a milestone in the relation between attachment and affective self - regulation . using language , children can name their feelings , receive verbal and emotional feedback about their adequacy , and thus become supported in the effort to think about themselves and others . bateman and fonagy understand borderline personality disorder as a result of inadequate mirroring in early development . according to them , patients with borderline personality disorder have difficulty in mentalizing mainly in interpersonal and intimate situations , when they are most vulnerable to excesses in anxiety . deficits in mentalization prevent them from having a good enough buffer from affects and trigger fight or flight mechanisms . these observations are relevant for the conceptualization of addictions , having in mind the high percent of comorbidity with borderline personality disorder . intoxication impairs mentalization of own emotional states as well as those of the attachment figures . deficits in mentalization on the other hand contribute to an inclination for substance abuse under emotional stress caused by interpersonal conflicts with attachment figures . contrasting , but also complementing fonagy 's model , bouchard and lecours present a theory of mentalization focused on the development of thinking through binding of instinctual pressure in representative networks . this theory has roots in the psychosomatic research done by marty , krystal 's theory of emotions [ 11 , 23 ] , and piaget 's conceptualization of the child 's intellectual development from sensor - motor activity towards formal verbal thought . bouchard and lecours describe a complex process of psychic working through which prevents direct discharge into actions or somatizations . affects are here conceptualized as positively or negatively valanced psychological phenomena with a somato - motor tendency for action . the authors assume that representative deficits lead to an excess of excitation , which has not been transformed into a psychic conflict , that is , anxiety has not been mentalized . forms of impulsivity , addicted behavior , and somatization are interpreted from this point of view as an expression of accumulated drive impulses with no attributed psychological meaning . bouchard and lecours describe mentalization as a continuous process , functioning as immune system of the psyche , because it modifies external and internal pressures . normally , mentalizing contributes to the coherent and meaningful experience of one 's own psychic states . instead of acquiring this tolerable distance from direct affective pressure , drug addicts often suffer from severe anxiety and depression . these conditions are triggered by the deep conviction that the individual is helpless in regulating not only external reality but also his or her emotional states . substance abuse is the coping mechanism which replaces mental processing of helplessness , apathy and emptiness , and thus brings back temporary control . bateman & fonagy , for example , point that patients with alexithymia usually grow in families characterized by high levels of negative affect , difficulties in representation , and impaired recognition of emotional expressions , as well as scant discussion of emotions in the parent - child relationship . present more specific data about the relationship between alexithymia and substance use disorders . in a sample of 204 patients ( 72 treated for alcoholism , 79 for drug addiction , and 53 for double addiction ) 41.7% were diagnosed as alexithymic , the percentage of alexithymia being significantly higher among women ( 50% ) than the corresponding figure among men ( 35.8% ) . high levels of alexithymia in substance use disorders contrast low levels ( 9% and 12% ) among male adults and students in norm , and 8% and 12% among women , respectively . there is also a growing body of research supporting the foundations of mentalization theory in various clinical groups and ages . taubner et al . show that depressed patients tend to have lower reflective functioning scores concerning issues of loss compared to healthy controls . the cited research fails to show the relation between reflective functioning and symptomatology in depressed or psychotic patients . however , lecours and bouchard present data that the severity of symptoms in the borderline personality disorder is associated with low level of mentalization in two distinct areas depressive and aggressive affects . furthermore , traumatized individuals are likely to meet the dsm - iv criteria for borderline personality disorder only if they have deficiencies in mentalizing . it is clear that the complex links between severity of symptoms and quality of mentalization should be further explored . from the point of view of the relation between mentalization and stress , it is becoming clear that relative calmness supports mentalization , while excessive anxiety contradicts it . an evident parallel exists with addictions , where an inability to contain affects , which is a basic component of mentalization , could be used as a key psychodiagnostic characteristic . looking at this promising line of investigations , it is surprising that there is hardly any published research on drug addicted patients ' mentalizing functioning . levy and truman , however , report data showing that cocaine - using mothers ' maternal mentalization mediates associations between maternal substance abuse and children 's psychosocial development . improvement in mentalization in response to a mentalization - based parenting intervention was associated with improvement in maternal caregiving behavior and increased regulation in children between 24 and 36 months of age . examine children exposed to parental methamphetamine abuse and find that those with higher mentalization were less prone to underreport symptoms , had fewer mental health problems , and were rated by their caregivers as more socially competent . the apparent scarcity of empirical research on mentalization in addicted patients stands in contrast to the fact that the presented models have already been operationalized successfully . the most widely used instrument for mentalization assessment is the scale for reflective functioning in the adult attachment interview ( aai ) . low results on that scale are registered if the subject demonstrates poor access to the motivational origins of behavior . the grille de l'laboration verbale des affects ( geva ) offers an alternative empirical approach . it consists of two orthogonal dimensions depending on the level of mentalization : four channels of affect expression ( somatic and motor activity , imagery and labeling verbalization ) and five levels of affect tolerance and abstraction ( disruptive impulsion , modulated impulsion , externalization , appropriation , and meaning association ) . these are a total of 20 possible forms ( 4 channels 5 levels ) of affective expression . there is a common agreement that the treatment of drug addictions has to offer an encompassing range of services medical , social , and psychological . the place of psychotherapeutic work is without doubt central because it is directed at changing the psychic functioning of the patient . it is assumed that this happens through a gradual process which deepens the understanding of the place of addiction in one 's own life . it is well known that early attempts at psychotherapeutic work with addicted patients offered no base for optimism . we are familiar with these individuals ' proneness to fall into relapse and drop out of therapy , as well as low tolerance for psychic pain combined with tendency for self - destructive behavior . contemporary psychodynamic forms of treatment of personality disorders , however , show a promising approach , focused on the current mental states of the patient . aiming to create a network of representations of these internal states , mentalization - based treatment ( mbt ) follows a different path from the traditional psychoanalytic technique . it does not aim at interpreting deep unconscious fantasies but works instead with easily accessible content . the therapist 's goal is to restore mentalizing by creating representational coherence and integration of mental states . the approach that bateman and fonagy offer is well structured and focused on enhancing the working alliance and paying attention to the immediate interaction between the patient and the therapist . the therapist is flexible to the specifics of the pathology ( impulsiveness , interpersonal difficulties , self - destructive behavior , etc . ) by being relatively active and encouraging a strong relation of attachment which makes it possible for both participants to explore and overcome current failures in mentalizing . mbt explores the relationship between affect and belief and has some technical features similar to cognitive behaviour therapy , which explores the relationship between maladaptive schema and dysfunctional cognition or problematic feeling and has been widely used to treat drug addiction . of course , to the extent of focusing on the here and now patient - therapist relationship , and of placing an emphasis on transference ( albeit not interpreting it actively ) , mbt is still psychodynamic psychotherapy . this approach has already been extensively studied in several randomized control trials with patients with personality disorders . bateman and fonagy , for example , report an 8-year followup of 41 patients with borderline personality disorder in partial hospitalization . mbt is associated with significant improvement in all measured areas ( depressive symptoms , suicidal and self - destructive behavior , number and duration of hospitalizations , social and interpersonal functioning , and use of psychopharmacological medication ) . the improvement is sustained 5 years after the end of therapy , while patients in treatment as usual show limited change or even deteriorate during the same period . this data should be considered having in mind that mbt requires relatively little additional training on top of general mental health training , and has been implemented in research studies by community mental health professionals , primarily nurses , with limited training given modest levels of supervision . this is an important aspect from the point of view of delivering cost - effective interventions . however , studies of the efficacy of this approach with drug addicted patients still have to be carried out . disorders of affect mentalization in drug addicts find different explanations in the light of the conflict - deficit dilemma . authors like khantzian stay closer to the mentalization models and see the lack of self - regulatory functions as an ego deficit , that is , a function that was never established , while , according to krystal , self - caring is forbidden by archaic parental figures . in that sense , krystal 's position is analogous to the classic psychoanalytic perspective , explaining addictions as a result of unconscious conflicts . following fonagy 's work and staying more closely with khantzian we understand low abilities for mentalization in addicted patients as a personality deficit related to early environmental failures . from this point of view mentalization - based theories stress predominantly the relational aspects in the functioning of the patients against the intrapsychic dimension of the traditional psychodynamic theories . usually these individuals share a history of interaction with a caregiving figure , which had not provided good enough mirroring or it was discontinued due to a trauma . this focus on the direct interpersonal environment , typical for fonagy 's theorizing , however , has been criticized for an underestimation of complex object relations which modulate affect activation . indeed , de - emphasis of the unconscious is a central feature in fonagy 's theory . at the same time , as diamond and kernberg also point out , fonagy and his colleagues show significant empirical evidence that mentalization is established in the context of secure attachment and is blocked in insecure attachment and/or severe trauma . choi - kain and gunderson add several critiques to the mentalization theory based on the idea that this concept is too broad and multidimensional . however , its core measure the reflective functioning scale , yields only a single score and it is time - consuming to administer . the authors propose that research should focus on more limited concepts for which self - report measures have been developed ( i.e. , theory of mind , mindfulness , empathy , etc . ) . another limitation , according to them , in the fonagy model is emphasizing process over content . other authors ( i.e. , ) have been trying to answer the question whether the concept of mentalizing is just a new word for well - known phenomena . it becomes clear , however , that it offers a pragmatic integration of clinical observations , developmental psychopathology , and attachment experiences . last but not least , mentalization combines psychodynamic hermeneutics with evidence - based practice and is open to advances in contemporary neurocognitive theories . strength in fonagy 's mentalization model and the classically oriented model of bouchard and lecours can be regarded as genuinely integrative theories uniting the intersubjective - relational approach with the drive / conflict perspective . an important point of distinction , however , is that fonagy 's theory underlines the interaction with a real object attributing meanings to the child 's affective states , while bouchard and lecours focus primarily on the role of representative mechanisms in verbal affect mentalization . so , although the two perspectives are not completely contradictory , fundamental in bouchard and lecours ' theory are the organizing structures of unconscious subjective experience . looking at the empirical evidence , we can see that these two approaches are distinct but also overlapping . high levels of reflective functioning or elaboration of affect contribute to a basic feature of mentalization the capacity to treat behavior as driven by internal mental events and not just external stimuli . deficits in capabilities for affect representation and modulation manifested in drug - addicted patients point to similar psychogenetic origins of mentalization disorders with psychosomatic conditions . better clinical understanding of this form of pathology is a key ingredient in the assessment and clinical work with drug - addicted patients . based on a coherent understanding of personality organization , mentalization models offer promising potential for psychodiagnostic accuracy and therapeutic efficacy . their corresponding operationalized instruments can be used as valuable tools for assessment of change in psychic functioning resulting from treatment . further work is recquired on distinguishing between different subgroups in the addicted population ( i.e. , a comparison of specific impairments of the reflective function and pathways to addiction in opiate and stimulant users ) .
traditionally treated with wariness , drug addictions have provoked a serious interest in psychodynamically oriented clinicians in recent decades . this paper discusses the development of contemporary psychodynamic conceptualizations of addictions , focusing specifically on mentalization - based theories . the concept of mentalization refers to a complex form of self - regulation which includes attribution of psychological meaning to one 's own behavior and affective states , as well as those of the others . we hypothesize that drug - addicted patients have severe impairments in mentalizing , associated with developmental deficits , characteristic for the borderline personality disorder and psychosomatic conditions . psychodynamic models of mentalization and their corresponding research operationalizations are reviewed , and implications for a contemporary understanding of drug addictions and psychotherapy are drawn . the authors propose that mentalization - oriented theories provide an adequate conceptualization , which is open to empirical testing and has clear and pragmatic guidelines for treatment .
several attempts to find the early counterparts of big spheroids in large areas of the sky at high redshifts have been conducted but to date just a handful of candidates have been found [ 10 ] . where are these bright objects hiding ? in galaxy formation models based on the hierarchical merging of dark matter halos the majority of large spheroids are formed at lower redshifts , so that the present - day large systems were previously broken - up into small fainter pieces of a yet not completely assembled whole [ 8 ] . there is also a good possibility that some large spheroids may have gone undetected as the host galaxies of bright qsos . two pieces of observational evidence support this hypothesis . first , a significant number of nearby bright qsos are associated with luminous ellipticals [ 3 ] . secondly , many of the properties of high-@xmath5 qsos are consistent with their association with the cores of early luminous spheroids . among them , the high metal content of the broad line region of high-@xmath5 qsos [ 6 ] ; the detection of large masses of dust in @xmath6 qsos [ 7 ] ; and the correspondence of the observed luminosity function of qsos and ellipticals [ 11 ] , do suggest that qso activity might be occurring in the central regions of young massive ellipticals . all these points are reinforced by the recent discovery that about 5 to 20% of the luminosity of both radio - loud and radio - quiet qsos at @xmath0 arises from extended structures of fwhm@xmath7 arcsec [ 1,2,9 ] . unraveling the nature of the extensions around qsos at these redshifts is of major importance since they could be revealing the hidden signature of the elusive early large spheroid population . in this contribution we focus our attention on the multicolour properties of the hosts of three @xmath0 qsos , in an attempt to characterize the emission mechanism . the three qsos , two radio - quiet 1630.5@xmath83749 and q 2244@xmath90105 , one radio - loud pks 2134@xmath8008 , were observed in the harris @xmath2 and @xmath3 passbands with the auxiliary port of the 4.2 m william herschel telescope ( wht ) at the observatorio de roque de los muchachos in la palma , and in @xmath4 band with the cassegrain focus of the 3.5 m at the observatorio de calar alto in almera ( spain ) . the qsos were selected so as to have bright stars in the field ( @xmath10 arcsec ) , which enabled us to define the point spread function ( psf ) of each observation accurately ( see [ 1,2 ] for a detailed description of data and analysis ) . for each qso field , we defined a psf using the brightest of the closest stellar companion to the qso . we then subtracted a scaled version of the psf in order either a ) to produce zero counts in the center of the residuals or b ) to achieve a flat - top profile with no depression in the center . we regard these quantities as lower limits ( 37% of the qso luminosity ) and best estimates ( 618% of the qso luminosity ) , respectively , of the total luminosity of these extended components . we have detected @xmath2 and @xmath3-band residuals revealing hosts in the three qsos . in all cases , the fwhm of the flat - top residual profiles ( @xmath11 to @xmath12 ) are significantly larger than the fwhm of the stars in each field ( typically 0.7 ) see in figure 1 the residuals left in our best detection case , 1630.5@xmath83749 . = 5.5 in figure 1 : countour plots of @xmath2 and @xmath3-band residuals after performing a psf subtraction that leaves zero counts in the center ; and @xmath4-band radial profiles of qso ( squares ) and star ( crosses ) , normalized to their central flux . the hosts we have detected have luminosities that contribute between 5 and 12% of the luminosity of the qsos ( nucleus@xmath8extension ) both in @xmath2 and @xmath3-bands ( and rest - frame ) . if the excess over the stellar @xmath4-profile of 1630.5@xmath83749 at @xmath13 is real , the @xmath4-band ( rest - frame ) luminosity of the host as derived from the measured colours would also contribute to the total @xmath4-band qso luminosity about 5% . our measurements indicate large and luminous extended systems ( @xmath14 kpc , @xmath15 to 22 mag ) . we will consider two alternative explanations for their nature : scattered light from the active nucleus and stellar light . large structures detected in high - redshift radio - galaxies have been attributed to light scattered from the active nucleus by a powerful transverse radio - jet . indeed , recent spectro - polarimetry of two @xmath16 radio - galaxies that exhibit alignment effects ( optical structures oriented in the direction of the radio - jet ) indicates that around 80% of the total uv continuum emission at rest - frame is non - stellar scattered light [ 5 ] . since radio - galaxies and radio - loud qsos could be identical objects viewed from different angles , an important amount of scattered light may be present around radio - loud nuclei . the host of the core - dominated radio - loud qso studied in this paper , pks 2134@xmath8008 , has an @xmath17 colour that is 0.52 mag redder than the nucleus . this argues against the simple optically - thin scattering case , which would yield colours as blue as or bluer than the nucleus itself . the @xmath18 limits for this host ( @xmath19 mag ) are not deep enough to probe the optically - thin scattering case value . note that four lobe - dominated radio - loud qsos at @xmath20 [ 9 ] have hosts with @xmath21 colours redder than the nuclei . however the @xmath21 ( or @xmath18 ) analysis discriminates poorly the origin of the light below the break , since scattered light would contribute predominantly in @xmath22-band ( rest frame ) and stellar light would contribute predominantly in @xmath4-band ( rest - frame ) . the host of our radio - quiet qso 1630.5@xmath83749 , exhibits the same general properties , with colours 0.25 and 0.8 mag redder than the nucleus in @xmath17 and @xmath18 , respectively . these colours are inconsistent with the optically - thin scattering case as an explanation for the uv hosts of our qsos . an optically - thick medium should be invoked in order to produce colours redder than those of the scattered source , but then the geometry of the scatterers should not be symmetrical since we still see the blue colours of the nucleus itself . this could be an alternative mechanism for the origin of the extended light in our sample , although there is no evidence in general for asymmetric scattering in radio - quiet qsos . stellar light remains still the most plausible interpretation for the extended light we have detected . the colours , sizes , luminosities and radial profiles are indeed in agreement with those expected from young stellar populations : \a ) the _ colours _ of the hosts , @xmath23 mag for 1630.5@xmath83749 and @xmath24 for pks 2134@xmath8008 and q 2244@xmath90105 , are not consistent with the colours predicted from a simple passively evolved stellar population , usually assumed to be characteristic of elliptical galaxies . a passively - evolved stellar population for a @xmath25 elliptical galaxy has colours @xmath26 mag and slightly bluer for a mild amount of activity [ 4 ] . younger populations are necessary in order to account for the blue colours observed in our hosts . as an example , typical nearby h ii galaxies set at @xmath27 would have colours as blue as @xmath28 , as derived from their characteristic flat spectral energy distributions ( sed ) : @xmath29 , with @xmath30 . \b ) and c ) the _ luminosities and radii _ of our hosts lie along the luminosity radius relationship of the local young h ii galaxies [ 2 ] . and there is at least one local h ii galaxy that is as big and luminous as our hosts . \d ) the _ radial profiles _ of the @xmath2 and @xmath3-band hosts , derived from the flat - top solutions , fall approximately as @xmath31-laws or exponential profiles for radii @xmath32 arcsec [ 2 ] . profiles derived for radii smaller than the fwhm of the observations are usually unreliably recovered by flat - top subtractions , as shown by our numerical simulations of galaxy@xmath8psf . therefore , the hosts of @xmath33 high - luminosity radio - quiet and radio - loud qsos are large and luminous , rivaling the most luminous nearby star forming galaxies . colours , sizes , luminosities and radial profiles are compatible with the interpretation of the extended light as a young galaxy . if all the uv luminosity is coming from a stellar population , the implied star formation rates ( in the continuous star formation case ) are sfr@xmath34 /yr on scales of @xmath14 kpc . these values are about an order of magnitude higher than those derived for field galaxies at similar redshifts found by lyman break searches in the hubble deep field . at @xmath35 , an unevolved @xmath36 galaxy with sed typical of a star - forming galaxy would appear to be about 3 mag fainter than the hosts we have detected . the density of high - luminosity qsos ( @xmath37 mag ) at redshifts between @xmath38 is about 10 gpc@xmath39 . this means that the density of large luminous galaxies like the ones considered here should be about 8 gpc@xmath39 at @xmath40 , taking into account the non - detection cases of extensions [ 1 ] and the relative under - abundance of radio - loud qsos , which form less than 10% of the qso population .
three high - redshift ( @xmath0 ) and high luminosity ( @xmath1 mag for 0 = 50 , 0p5 ) qsos , two radio - quiet one radio - loud , were imaged in @xmath2 , @xmath3 and @xmath4 bands . the luminosities , colours and sizes of the hosts overlap with those of actively star - forming galaxies in the local universe . these properties give support to the young host galaxy interpretation of the extended light around qsos at high - redshift . the rest - frame uv and uv - optical colours are inconsistent with the hypothesis of a scattered halo of light from the active nucleus by a simple optically - thin scattering process produced by dust or hot electrons . if the uv light is indeed stellar , star formation rates of hundreds of solar masses per year are implied , an order of magnitude larger than in field galaxies at similar redshifts and above . this might indicate that the qso phenomenon is preferentially accompanied by enhanced galactic activity at high - redshift . psfig epsf # 1_#1 _ # 1_#1 _ = # 1 1.25 in .125 in .25 in 0 0 50 0p5 0
SECTION 1. SHORT TITLE. This Act may be cited as the ``National African American Museum Act''. SEC. 2. FINDINGS. (a) Findings.--The Congress finds that-- (1) the presentation and preservation of African American life, art, history, and culture within the National Park System and other Federal entities are inadequate; (2) the inadequate presentation and preservation of African American life, art, history, and culture seriously restrict the ability of the people of the United States, particularly African Americans, to understand themselves and their past; (3) African American life, art, history, and culture include the varied experiences of Africans in slavery and freedom and the continued struggles for full recognition of citizenship and treatment with human dignity; (4) in enacting Public Law 99-511, the Congress encouraged support for the establishment of a commemorative structure within the National Park System, or on other Federal lands, dedicated to the promotion of understanding, knowledge, opportunity, and equality for all people; (5) the establishment of a national museum and the conducting of interpretive and educational programs, dedicated to the heritage and culture of African Americans, will help to inspire and educate the people of the United States regarding the cultural legacy of African Americans and the contributions made by African Americans to the society of the United States; and (6) the Smithsonian Institution operates 15 museums and galleries, a zoological park, and 5 major research facilities, none of which is a national institution devoted solely to African American life, art, history, or culture. SEC. 3. ESTABLISHMENT OF THE NATIONAL AFRICAN AMERICAN MUSEUM. (a) Establishment.--There is established within the Smithsonian Institution a Museum, which shall be known as the ``National African American Museum''. (b) Purpose.--The purpose of the Museum is to provide-- (1) a center for scholarship relating to African American life, art, history, and culture; (2) a location for permanent and temporary exhibits documenting African American life, art, history, and culture; (3) a location for the collection and study of artifacts and documents relating to African American life, art, history, and culture; (4) a location for public education programs relating to African American life, art, history, and culture; and (5) a location for training of museum professionals and others in the arts, humanities, and sciences regarding museum practices related to African American life, art, history, and culture. SEC. 4. LOCATION AND CONSTRUCTION OF THE NATIONAL AFRICAN AMERICAN MUSEUM. The Board of Regents is authorized to plan, design, reconstruct, and renovate the Arts and Industries Building of the Smithsonian Institution to house the Museum. SEC. 5. BOARD OF TRUSTEES OF MUSEUM. (a) Establishment.--There is established in the Smithsonian Institution the Board of Trustees of the National African American Museum. (b) Composition and Appointment.--The Board of Trustees shall be composed of 23 members as follows: (1) The Secretary of the Smithsonian Institution. (2) An Assistant Secretary of the Smithsonian Institution, designated by the Board of Regents. (3) Twenty-one individuals of diverse disciplines and geographical residence who are committed to the advancement of knowledge of African American art, history, and culture appointed by the Board of Regents, of whom 9 members shall be from among individuals nominated by African American museums, historically black colleges and universities, and cultural or other organizations. (c) Terms.-- (1) In general.--Except as provided in paragraph (2), members of the Board of Trustees shall be appointed for terms of 3 years. Members of the Board of Trustees may be reappointed. (2) Staggered terms.--As designated by the Board of Regents at the time of initial appointments under paragraph (3) of subsection (b), the terms of 7 members shall expire at the end of 1 year, the terms of 7 members shall expire at the end of 2 years, and the terms of 7 members shall expire at the end of 3 years. (d) Vacancies.--A vacancy on the Board of Trustees shall not affect its powers and shall be filled in the manner in which the original appointment was made. Any member appointed to fill a vacancy occurring before the expiration of the term for which the predecessor of the member was appointed shall be appointed for the remainder of the term. (e) Noncompensation.--Except as provided in subsection (f), members of the Board of Trustees shall serve without pay. (f) Expenses.--Members of the Board of Trustees shall receive per diem, travel, and transportation expenses for each day, including traveltime, during which they are engaged in the performance of the duties of the Board of Trustees in accordance with section 5703 of title 5, United States Code, with respect to employees serving intermittently in the Government service. (g) Chairperson.--The Board of Trustees shall elect a chairperson by a majority vote of the members of the Board of Trustees. (h) Meetings.--The Board of Trustees shall meet at the call of the chairperson or upon the written request of a majority of its members, but shall meet not less than 2 times each year. (i) Quorum.--A majority of the Board of Trustees shall constitute a quorum for purposes of conducting business, but a lesser number may receive information on behalf of the Board of Trustees. (j) Voluntary Services.--Notwithstanding section 1342 of title 31, United States Code, the chairperson of the Board of Trustees may accept for the Board of Trustees voluntary services provided by a member of the Board of Trustees. SEC. 6. DUTIES OF THE BOARD OF TRUSTEES OF THE MUSEUM. (a) In General.--The Board of Trustees shall-- (1) recommend annual budgets for the Museum; (2) consistent with the general policy established by the Board of Regents, have the sole authority to-- (A) loan, exchange, sell, or otherwise dispose of any part of the collections of the Museum, but only if the funds generated by such disposition are used for additions to the collections of the Museum or for additions to the endowment of the Museum; (B) subject to the availability of funds and the provisions of annual budgets of the Museum, purchase, accept, borrow, or otherwise acquire artifacts and other property for addition to the collections of the Museum; (C) establish policy with respect to the utilization of the collections of the Museum; and (D) establish policy regarding programming, education, exhibitions, and research, with respect to the life and culture of African Americans, the role of African Americans in the history of the United States, and the contributions of African Americans to society; (3) consistent with the general policy established by the Board of Regents, have authority to-- (A) provide for restoration, preservation, and maintenance of the collections of the Museum; (B) solicit funds for the Museum and determine the purposes to which those funds shall be used; (C) approve expenditures from the endowment of the Museum, or of income generated from the endowment, for any purpose of the Museum; and (D) consult with, advise, and support the Director in the operation of the Museum; (4) establish programs in cooperation with other African American museums, historically black colleges and universities, historical societies, educational institutions, cultural and other organizations for the education and promotion of understanding regarding African American life, art, history, and culture; (5) support the efforts of other African American museums, historically black colleges and universities, and cultural and other organizations to educate and promote understanding regarding African American life, art, history, and culture, including-- (A) development of cooperative programs and exhibitions; (B) identification, management, and care of collections; (C) participation in the training of museum professionals; and (D) creating opportunities for-- (i) research fellowships; and (ii) professional and student internships; (6) adopt bylaws to carry out the functions of the Board of Trustees; and (7) report annually to the Board of Regents on the acquisition, disposition, and display of African American objects and artifacts and on other appropriate matters. SEC. 7. DIRECTOR AND STAFF. (a) In General.--The Secretary of the Smithsonian Institution, in consultation with the Board of Trustees, shall appoint a Director who shall manage the Museum. (b) Applicability of Certain Civil Service Laws.--The Secretary of the Smithsonian Institution may-- (1) appoint the Director and 5 employees of the Museum, without regard to the provisions of title 5, United States Code, governing appointments in the competitive service; and (2) fix the pay of the Director and such 5 employees, without regard to the provisions of chapter 51 and subchapter III of chapter 53 of such title, relating to classification and General Schedule pay rates. SEC. 8. DEFINITIONS. For purposes of this Act: (1) The term ``Board of Regents'' means the Board of Regents of the Smithsonian Institution. (2) The term ``Board of Trustees'' means the Board of Trustees of the National African American Museum established in section 5(a). (3) The term ``Museum'' means the National African American Museum established under section 3(a). (4) The term ``Arts and Industries Building'' means the building located on the Mall at 900 Jefferson Drive, S.W. in Washington, the District of Columbia. SEC. 9. AUTHORIZATION OF APPROPRIATIONS. -T-h-e-r-e -a-r-e -a-u-t-h-o-r-i-z-e-d -t-o -b-e -a-p-p-r-o-p-r-i-a-t-e-d -t-o -c-a-r-r-y -o-u-t -t-h-i-s -A-c-t -$-5-,-0-0-0-,-0-0-0 -f-o-r -f-i-s-c-a-l -y-e-a-r -1-9-9-4 -a-n-d -s-u-c-h -s-u-m-s -a-s -m-a-y -b-e -n-e-c-e-s-s-a-r-y -f-o-r -e-a-c-h -o-f -t-h-e -s-u-c-c-e-e-d-i-n-g -f-i-s-c-a-l -y-e-a-r-s-. -A-m-o-u-n-t-s -a-p-p-r-o-p-r-i-a-t-e-d -p-u-r-s-u-a-n-t -t-o -t-h-i-s -s-e-c-t-i-o-n -s-h-a-l-l -b-e -a-v-a-i-l-a-b-l-e -o-n-l-y -f-o-r -c-o-s-t-s -d-i-r-e-c-t-l-y -r-e-l-a-t-i-n-g -t-o -t-h-e -e-s-t-a-b-l-i-s-h-m-e-n-t -a-n-d -o-p-e-r-a-t-i-o-n -o-f -t-h-e -M-u-s-e-u-m-. There are authorized to be appropriated such sums as may be necessary only for costs directly relating to the operation and maintenance of the Museum. Passed the House of Representatives June 29 (legislative day, June 28), 1993. Attest: DONNALD K. ANDERSON, Clerk.
National African American Museum Act - Establishes within the Smithsonian Institution the National African American Museum (the Museum) to be operated as a center for scholarship and a location for museum training, public education, exhibits, and collection and study of items and materials relating to the life, art, history, and culture of African Americans. Authorizes the Board of Regents of the Smithsonian Institution to plan, design, reconstruct, and renovate the Arts and Industries Building to house the Museum. Establishes a Board of Trustees of the Museum in the Smithsonian Institution. Sets forth various duties of the Board of Trustees, including: (1) establishing and supporting cooperative programs with other museums and institutions; and (2) reporting annually to the Board of Regents. Directs the Secretary of the Smithsonian Institution to appoint a Director to manage the Museum (as well as appointing five other Museum employees). Authorizes appropriations only for costs directly relating to the operation and maintenance of the Museum.
van gompel et al . ( 2005 ) explain their data in terms of a special type of reanalysis model called the unrestricted race model . in case of ambiguous input , the parser is assumed to explore , in parallel , all possible analyses of the new input word . the parser may be biased in favor of one or more of the alternative analyses due to prior syntactic as well as non - syntactic information , to syntactic complexity , or otherwise . the prior information includes the meaning computed for the input string up to and including the input word that was processed last . the parser adopts the analysis that finishes first , i.e. , wins the speed race , and discards all other ones . if subsequent words can not be assigned a satisfactory or plausible analysis , the parser is forced to backtrack and to reanalyze ( part of ) the input string . the model is a syntax - first model because the initial analysis of a novel input word does not take the meaning of this word into account but only its part - of - speech ( major word - class ) feature . ( however , as said before , any biases resulting from prior syntactic and non - syntactic information are supposed to make themselves felt here . ) the sentence materials the participants in van gompel et al.s experiments had to read in the ga condition , had been carefully prepared so as to exclude a strong a priori preference for a low or high attachment interpretation . this implies that the processor settles on attaching the verb of the relative clause high and low with roughly equal proportions : the two attachments win the race about equally often . as they both yield a plausible meaning , no reanalysis needs to be carried out . in the two la conditions , however , when the meaning of the verb is accessed and integrated with the meaning of the current input string ( e.g. , province - retiring ) , the parser s initial attachment site for the verb of the relative clause turns out to be wrong in about half the trials . hence , reanalysis will occur in roughly 50% of the trials and manifest itself in prolonged reading times due to among other things a higher incidence of regressive eye - movements ( eye fixations on earlier text regions ; regressions for short ) . the unrestricted race model is not the only possible interpretation . consider a slightly but essentially different version where the syntactic processor is operating in parallel with the non - syntactic processors ( cf . jackendoff ( 2002 ) and kuperberg ( 2007 ) ) . specifically , the syntax - first assumption of the unrestricted race model is dropped and the syntactic races for an attachment site of a new ambiguous input word proceed in parallel with the construction of a plausible conceptual interpretation . the conceptual processor can work in a manner similar to the syntactic processor , except that its decisions are founded on conceptual rather than syntactic constraints and preferences . the conceptual constraints derive from the meanings of the content words , and from the meaning implications entailed by inflections and function words ( e.g. , the genitive morpheme attached to governor in the governor s province and the function word of in the province of the governor are both interpretable as expressing a possessive relationship ) . thus , the conceptual processor builds its own hierarchical representation of the current input sentence in parallel to the syntactic representation . in simple cases ( e.g. , the dog bit the man ) , the first conceptual representation that the conceptual processor proposes without having taken syntactic information into account , will dovetail with the first syntactic representation proposed by the syntactic processor . if in more complex cases , such as the dog was bitten by the man , the preferred conceptual analysis happens to conflict with the preferred syntactic parse ( cf . ferreira ( 2003 ) ) , a revision will have to be negotiated between the parallel processors . in terms of the la examples ( 2 ) and ( 3 ) , the conceptual processor quickly determines that governor , but not province , is a plausible actor of retire events . simultaneously with this conceptual analysis , the race for high versus low attachment of retiring takes place within the syntactic processor . after both the syntactic and conceptual processors have finished , a comparison stage follows which checks whether the output structures they produced are compatible . in the two la - conditions , the predictions from this parallelized version of the unrestricted race model coincide with those of the original serial version : in the ga condition , the probability of a mismatch is zero . a second option adds interactivity between syntactic and non - syntactic processing but drops the separate comparison stage . for the sake of simplicity , let us restrict ourselves to two processors one syntactic , one conceptual which are dealing with syntactically and conceptually correct input sentences . the first two about how the processors inform one another , the last one about how eye - movements respond to reanalysis : whenever a decision has been made by one of the linguistic processors , it is immediately communicated to the other one.a processor that is informed about a decision reached by the other one , immediately checks whether it is compatible with ( one of ) the option(s ) allowed by the current internal state , and discards incompatible options.if , after terminating its work on the current input , a processor is left without acceptable analyses , it initiates reanalysis , which may cause regressive eye movements . whenever a decision has been made by one of the linguistic processors a processor that is informed about a decision reached by the other one , immediately checks whether it is compatible with ( one of ) the option(s ) allowed by the current internal state , and discards incompatible options . if , after terminating its work on the current input , a processor is left without acceptable analyses , it initiates reanalysis , which may cause regressive eye movements . what does this entail with respect to the ga and la sentences ( 1 ) through ( 3 ) ? there are two possibilities the conceptual processor reaching a decision prior to the syntactic processor ( i.e. , it settles on a conceptual attachment without being informed by syntactic information ) , or vice - versa . suppose that for whatever reason the conceptual processor decides to select governor as the actor of retire , and that this decision reaches the syntactic processor prior to the latter having chosen an attachment site for the relative clause . the syntactic processor then easily verifies that this conceptual choice corresponds to a low attachment site , and immediately adopts this decision , which fits the current syntactic tree . the same final conclusion follows when the conceptual processor prefers bodyguard as the actor of retiring . in cases where the syntactic processor manages to take an attachment decision before the conceptual processor makes its choice if the conceptual processor reaches its conclusion ahead of the syntactic processor , the latter will never fail to accommodate this conclusion because the corresponding attachment site is always available . conversely , if syntactic processing terminates prior to conceptual processing , it may have selected an attachment site that the conceptual processor refuses to adopt e.g . , interpreting province as the actor of retiring how does the model proposed in this section differ from the constraint - based parallelinteractive models targeted by van gompel et al . first of all , in current constraint - based models , the processors ( information sources ) can not initialize reanalysis individually . instead , the information recruited by these sources is pooled together ( integrated ) and eye movements are affected only after an overall decision has been reached . the second aspect concerns the decision - making mechanism itself , which is based on competition between alternative analyses . if the pooled information clearly supports one of the alternative analyses to the detriment of the other one(s ) , the winner will emerge sooner than when the evidence is mixed . . found ( but see the unexpected computer simulation results reported by green and mitchell 20061 ) . however , the model outlined in the present section shows that parallelism of syntactic and conceptual processing can be realized in a model where two ( or more ) concurrent processors are engaged in a race to be the first to complete their jobs . this speed race model is faithful to van gompel et al.s ( 2005 ) empirical findings while lacking the monolithic pooling of syntactic and conceptual information typical of existing constraint - based models . the answer is negative : there may very well be competition within each ( or some ) of the linguistic processors . for instance , the selection of a suitable attachment site for the verb retiring within the syntactic parser could involve competition instead of a speed race . specifically , instead of constructing two or more independent parse trees for a syntactically ambiguous input string ( as happens in the unrestricted race model ) , in a competition model an incoming word or word group is tentatively and temporarily attached to all nodes of the current tree that are allowed by the grammar . the ensuing competion between alternative attachment sites is then resolved on the basis of factors such as the frequency or the complexity of the resulting syntactic configurations , the recency of the nodes to which the new input is attached , or their activation level . the details of the mechanism subserving competition within the syntactic processor need not concern us here . specific proposals have been made by , e.g. , stevenson ( 1993 , 1994 ) , kempen and vosse ( 1989 ) and vosse and kempen ( 2000 ) . similarly , within the conceptual processor there may be a competition for the selection of the role of actor of the retire concept . ( 2005 ) do not qualify as evidence against competition during syntactic ambiguity resolution . at best , their data count as evidence against the monolithic type of competition operating in current constraint - based models . modularized , less monolithic version of a parallel - interactive speed race model of ambiguity resolution accounts for the eye tracking facts . competition can play an important role in such a model if it is positioned within the individual syntactic and conceptual processors .
in a recent series of publications ( traxler et al . j mem lang 39:55892 , 1998 ; van gompel et al . j mem lang 52:28407 , 2005 ; see also van gompel et al . ( in : kennedy , et al.(eds ) reading as a perceptual process , oxford , elsevier pp 62148 , 2000 ) ; van gompel et al . j mem lang 45:22558 , 2001 ) eye tracking data are reported showing that globally ambiguous ( ga ) sentences are read faster than locally ambiguous ( la ) counterparts . they argue that these data rule out constraint - basedmodels where syntactic and conceptual processors operate concurrently and syntactic ambiguity resolution is accomplished by competition . such models predict the opposite pattern of reading times . however , this argument against competition is valid only in conjunction with two standard assumptions in current constraint - based models of sentence comprehension : ( 1 ) that syntactic competitions ( e.g. , which is the best attachment site of the incoming constituent ? ) are pooled together with conceptual competitions ( e.g. , which attachment site entails the most plausible meaning ? ) , and ( 2 ) that the duration of a competition is a function of the overall ( pooled ) quality score obtained by each competitor . we argue that it is not necessary to abandon competition as a successful basis for explaining parsing phenomena and that the above - mentioned reading time data can be accounted for by a parallel - interactive model with conceptual and syntactic processors that do not pool their quality scores together . within the individual linguistic modules , decision - making can very well be competition - based .
SECTION 1. SHORT TITLE. This Act may be cited as the ``City of Yuma Improvement Act''. SEC. 2. DEFINITIONS. In this Act: (1) City.--The term ``City'' means the city of Yuma, Arizona. (2) Federal land.--The term ``Federal land'' means the Bureau of Reclamation land depicted on the map and more particularly described as-- (A) parcels 2 and 3 of tract 1; (B) a portion of parcel 110-73-019; (C) the old Arizona Department of Transportation weigh station; (D) portions of blocks 52, 53, 54, and 55; (E) the future drying bed location; and (F) the future Arizona Welcome Center. (3) Map.--The term ``map'' means the map entitled ``City of Yuma Proposed Property Ownership'' and dated July 25, 2005. (4) Non-federal land.--The term ``non-Federal land'' means the non-Federal land depicted on the map and generally known as the ``Railroad Parcels''. (5) Secretary.--The term ``Secretary'' means the Secretary of the Interior. SEC. 3. CONVEYANCE OF FEDERAL LAND AND NON-FEDERAL LAND. (a) In General.--Subject to valid existing rights, easements, and rights-of-way, and in accordance with this Act, the Secretary shall convey all right, title, and interest of the United States in and to the Federal land to the City in exchange for the non-Federal land. (b) Title to Non-Federal Land.-- (1) In general.--On receipt of a deed conveying to the United States fee simple title to the non-Federal land that meets the requirements under paragraph (2), the Secretary shall record a deed from the United States that conveys to the City fee simple title to the Federal land. (2) Requirements.--Title to the non-Federal land shall-- (A) conform with the regulations and title approval standards of the Attorney General that are applicable to Federal land acquisitions; and (B) include all valid existing rights, easements, and rights-of-way. (c) Administration of Acquired Land.--The Secretary, acting through the Commissioner of Reclamation, shall administer the non-Federal land acquired by the Secretary. (d) Release From Liability.--Effective on the date of conveyance to the City of the parcel of Federal land under subsection (a), the United States shall not be liable for damages arising out of any act, omission, or occurrence relating to the Federal land and facilities conveyed, but shall continue to be liable for damages caused by acts of negligence committed by the United States or by any employee or agent of the United States before the date of conveyance, consistent with chapter 171 of title 28, United States Code. (e) Administrative Costs.--All administrative costs relating to the conveyance of the Federal land and non-Federal land under subsection (a) shall be paid by the City to the United States. (f) Valuation, Appraisals, and Equalization.-- (1) In general.--The value of the Federal and the non-Federal land-- (A) shall be equal, as determined by appraisals conducted in accordance with paragraph (2); or (B) if not equal, shall be equalized in accordance with paragraph (3). (2) Appraisals.-- (A) In general.--The Federal land and non-Federal land shall be appraised by an independent appraiser selected by the Secretary. (B) Requirements.--An appraisal conducted under subparagraph (A) shall be conducted in accordance with-- (i) the Uniform Appraisal Standards for Federal Land Acquisition; and (ii) the Uniform Standards of Professional Appraisal Practice. (C) Equalization of values.-- (i) In general.--If the value of the Federal land and the non-Federal land is not equal, the value may be equalized by-- (I) the Secretary making a cash equalization payment to the City; (II) the City making a cash equalization payment to the Secretary; or (III) reducing the acreage of the Federal land or non-Federal land, as appropriate. (ii) Disposition of proceeds.--Any cash equalization payments received by the Secretary under clause (i)(II) shall be deposited in the general fund of the Treasury. SEC. 4. CONVEYANCE OF UNITED STATES FISH AND WILDLIFE SERVICE LAND TO THE CITY OF YUMA. (a) In General.--Subject to valid existing rights, the Secretary shall convey to the City by quitclaim deed, all right, title, and interest of the United States in and to the parcel of United States Fish and Wildlife Service land located at 356 West First Street, Yuma, Arizona. (b) Consideration.--In exchange for the conveyance of land under subsection (a), the City shall pay to the Secretary consideration in an amount that reflects the fair market value of the land conveyed to the City under that subsection, as determined by an appraisal prepared in accordance with-- (1) the Uniform Appraisal Standards for Federal Land Acquisitions; and (2) the Uniform Standards of Professional Appraisal Practice. (c) Administrative Costs.--Any administrative costs relating to the conveyance of land under subsection (a) shall be paid by the City to the United States. (d) Disposition and Use of Proceeds.--Amounts paid to the Secretary under subsection (b) shall be available to the Secretary, without further appropriation and until expended, to pay-- (1) the administrative costs of the conveyance under subsection (a); and (2) the costs of constructing the Kofa National Wildlife Refuge headquarters and visitor center in Yuma, Arizona. Speaker of the House of Representatives. Vice President of the United States and President of the Senate.
City of Yuma Improvement Act - Directs the Secretary of the Interior to convey all U.S. interests in specified federal land in Arizona to the city of Yuma, Arizona, in exchange for specified nonfederal land (Railroad Parcels). Requires the Secretary, acting through the Commissioner of Reclamation, to administer the nonfederal land acquired. Requires all administrative costs relating to the conveyance of the federal and nonfederal land to be paid by the city to the United States. Requires an independent appraisal of the federal and nonfederal land in accordance with the Uniform Appraisal Standards for Federal Land Acquisition and the Uniform Standards of Professional Appraisal Practice. Requires the values of the federal and nonfederal land to be equal. Permits the equalization of unequal land values by means of cash equalization payments. Directs the Secretary to convey to the city, by quitclaim deed, in exchange for its fair market value, all U.S. interests in and to the parcel of land of U.S. Fish and Wildlife Service land located at 356 West First Street in Yuma. Requires the city, in exchange for such conveyance, to pay to the Secretary consideration in an amount that reflects the fair market value of the land conveyed to the city. Requires any administrative costs related to such conveyance to be paid by the city to the United States. Makes amounts paid to the Secretary as consideration available for: (1) the administrative costs of such conveyance to the city; and (2) the costs of constructing the Kofa National Wildlife Refuge headquarters and visitor center in Yuma.
@xmath0 carinae , situated in the carina complex at about 2.3kpc ( davidson & humphreys @xcite ) , is one of the most massive stars known in the galaxy and is going through the luminous blue variable phase ( humphreys & davidson @xcite ) of unsteady mass loss ( davidson et al . @xcite ) . during the 1840 s it underwent an outburst and reached visual magnitude -1 ; since then is has been emerging from the dust which condensed after this ejection ( walborn & liller , @xcite ) . long term monitoring of optical , ir , radio and x - ray spectra has revealed evidence of periodicity perhaps related to a binary or multiple star at the core of the nebula ( daminelli et al . @xcite ) . the compact nebula around @xmath0 carinae ( hd 93308 ) , called the homunculus , was first shown by thackeray ( @xcite ) to be highly polarized . the initial polarimetry was confirmed by wesselink ( @xcite ) who measured linear polarization of around 40% . visvanathan ( @xcite ) observed that the polarization centred on @xmath0 carinae was almost constant with wavelength from u to r and increased with increasing aperture size . in a small aperture , higher polarization was observed on the nw side of the nebula than on the se . the first systematic polarization maps were made by warren - smith et al . ( @xcite ) in the v band and demonstrated a centro - symmetric pattern of polarization vectors with a marked asymmetry in the polarization values along the major axis ( position angle @xmath6130@xmath5 ) with values upto 40% in the nw lobe . to produce such high values of polarization in a reflection nebula , mie scattering by silicate particles with a size distribution weighted to smaller particles was invoked and modelled by carty et al . ( @xcite ) . in the near ( @xmath70.5@xmath2 ) vicinity of @xmath0 car itself , speckle masking polarimetry in the h@xmath8 line and local continuum has revealed evidence for a compact equatorial disc aligned with the minor axis of the homunculus ( falcke et al . @xcite ) . within @xmath11@xmath2 of @xmath0 car the polarization vector pattern does not remain centrosymmetric in the r band , suggesting that local structures and perhaps intrinsic emission may contribute to the morphology and scattered light ( falcke et al . @xcite ) . polarimetry in the mid - infrared , where the dust emits rather than scatters radiation , shows an entirely different pattern of polarization vectors with a trend to be oriented radially , particularly near the boundary of the emission ( aitken et al . such a pattern can be interpreted in terms of emission from aligned grains ; aitken et al . ( @xcite ) suggest that the alignment mechanism may be gas - grain streaming , driven by the high outflow velocity , or a remnant magnetic field from a dense magnetized disc . there is a wealth of ir observations of @xmath0 car and the homunculus on account of its intrinsic ir brightness , first observed by westphal & neugebauer ( @xcite ) , and astrophysical interest . the ir spectrum is characterized by a peak around 10@xmath3 m , indicative of silicate grains ( mitchell & robinson , @xcite ) . there is a central ir point source together with a second peak on the minor axis of the nebula , whose separation increases from 1.1 to 2.2@xmath2 from 3.6 to 11.2@xmath3 m ( hyland et al . the near - ir spectrum of @xmath0 car shows a steep increase with wavelength and prominent hydrogen lines of the paschen and brackett series as well as he i lines ( whitelock et al . @xcite ) and weaker fe ii and [ fe ii ] lines ( altamore et al . @xcite ) . maps in the j , h and k bands show that the structure is dominated by scattering , but beyond about 3@xmath3 m dust emission dominates ( allen @xcite ) , with many clumps present . high spatial resolution observations have reported an unresolved central source ( at l and m band , bensammar et al . @xcite ) , with filaments and unresolved knots within 1@xmath2 detected in many ir bands ( gehring @xcite ) . maps in the mid - ir show a similar structure and the compact central source has a dust temperature @xmath6650k and dust mass of 10@xmath9m@xmath10 with nearby dusty clouds associated into loop features ( smith et al . this source has been so prodigiously studied at so many wavelengths that it possesses its own review article in annual reviews of astronomy and astrophysics ( davidson & humphries @xcite ) . @xmath0 car can be considered an ideal source for adaptive optics on account of its very bright central , almost point , source ( v@xmath67mag . - van genderen et al . @xcite ) and the limited radial extent ( @xmath1110@xmath2 ) of the homunculus , which means that the source itself can be used as a reference star for the wavefront sensor . as a consequence , off - axis anisoplaniticity does not significantly affect the adaptive optics ( ao ) correction out to the edges of the nebula . previous near - infrared ao imaging of @xmath0 car was obtained ( rigaut & gehring @xcite ) , including some limited polarimetry ( gehring @xcite ) using the come - on ao instrument . here we report on dedicated high resolution near - ir ao imaging polarimetry conducted at j , h , k , and in a continuum band at 2.15@xmath3 m , using the adonis system and sharp ii camera with the aim of studying the small - scale polarization structure of the homunculus . the observations are described in sect . 2 ; the reductions and polarization data are presented in sect . 3 and the relevance of the results for the structure and dust properties of this remarkable reflection nebula are discussed in sect . imaging polarimetry of @xmath0 carinae was obtained with the adonis adaptive optics instrument mounted at the f/8.1 cassegrain focus of the eso 3.6 m telescope . adonis is the eso common - user adaptive optics instrument ; it employs a 64 element deformable mirror and wave - front sensor ( beuzit et al . @xcite ) . for the observations of @xmath0 car , a reticon detector was used as the wave - front sensor . the camera is sharp ii - a rockwell 256@xmath12 hgcdte nicmos 3 array ( hofmann et al . the pixel scale was chosen as 0.050@xmath13 , giving a field of view of [email protected]@xmath2 . although this field does not encompass the full extent of the homunculus nebula it was chosen so that well - sampled diffraction limited imaging would be possible in at least the h and k bands . table 1 lists the observations ; the two orientations , referred to as a and b , had @xmath0 car in the lower right and upper left of the array respectively ( east is up ; north to the right ) enabling full coverage of the homunculus . the narrow band 2.15 @xmath3 m ( henceforth k@xmath4 ) observations were made with @xmath0 car in the centre of the array . for each filter and orientation , exposures were made at 8 position angles of the polarizer : 0.0 , 22.5 , 45.0 , 67.5 , 90.0 , 112.5 , 135.0 , 157.5@xmath5 in sequence . in addition a repeat of the 0@xmath5 exposure was made with the polarizer angle set to 180@xmath5 in order to check the photometry and repeatability of the polarimetric measurements . each full sequence of polarization measurements at the 8 + 1 position angles was repeated as specified in column 6 of table 1 . offset sky chopping was employed and the relative position of the offset sky is listed in column 5 of table 1 ; the exposure on sky was equal to the on - source time . as discussed in ageorges & walsh ( @xcite ) it was not possible to calculate reliable k band polarimetry ; these data will therefore only be discussed in terms of their high resolution imaging . on 1996 march 03 due to a technical problem , the computer control of the chopper malfunctioned and the offset sky had to be observed subsequent to each sequence of polarizer angles , and in some cases the exposure time on source was greater than on background sky . the last column of table 1 gives an indication of the external seeing as measured by the differential image motion monitor at la silla during the observations . photometric standards were not observed and no attempt has been made to determine accurate magnitudes in the j , h , k and k@xmath4 filters . [ cols= " < , > , > , > , > , > , > , > " , ] @xmath15 normalised to the observed value at 0.410@xmath3 m + one way to attempt to visualize the extinction is to examine the wavelength variation of scattered light emerging at a position where there is an extinction feature . a position such as the pronounced drop in surface brightness at @xmath161.3@xmath2 on the morse et al . ( @xcite ) cut ( fig . 6 ) appears to be promising . the fractional depth of this feature was measured relative to the peaks by linearly interpolating between the values at @xmath160.5 and @xmath162.0@xmath2 . this is clearly dependent on the spatial resolution , especially when it comes to estimating the peaks which are much sharper than the extinction hole . the result is given in table 2 expressed in magnitudes ( i.e. a@xmath17 from the wfpc2 and adonis measurements ) . for comparison the expected extinction for a galactic law matched to a@xmath18 is listed in column 3 ( using the seaton ( @xcite ) extinction law as parametrized by howarth @xcite and r=3.1 ) . for the morse et al . ( @xcite ) data , the f336w point appears anomalous ; it may be that the peaks also suffer extinction so the measurement of the extinction to the globule is underestimated . over the range 4100 - 10420 the extinction towards the nebula drops but less sharply than for the galactic extinction law . there is clearly a jump in values between the hst 1.042@xmath3 m and the adonis j band extinctions , probably on account of differing spatial resolution and psf s causing differing degrees of infilling . treating the measurements from j to k separately in table 2 shows that the extinction also drops less steeply than the galactic extinction curve , strengthening the suggestion of a flatter extinction law in this region of the homunculus . this somewhat greyer extinction favours particles larger than those typically found in the ism , in agreement with the conclusions of smith et al . ( @xcite ) and others on dust emission . davidson et al . ( @xcite ) also suggested grey extinction from a comparison of the modestly wavelength dependent brightening of @xmath0 carinae and the homunculus in the optical and near - ir . there is a strong discrepancy between the predictions of the extinction and emission of grains in the homunculus and their polarization properties . if the grains were typically 1 - 2@xmath3 m in the homunculus , mie theory for spherical particles predicts a maximum polarization at 1.65@xmath3 m of 38% for a scattering angle of 120@xmath5 ( assuming that the size distribution is flat from 1 - 2@xmath3 m and using the draine ( @xcite ) optical constants for silicate grains ) . however the v band polarization from mie theory is only 13% for such a size range of particles at the same scattering angle . whilst rayleigh scattering from very small @xmath190.1@xmath3 m grains produces a similar polarization at all wavelengths , it produces only a small variation in scattered flux with scattering angle ( by a factor @xmath62 ) . thus rayleigh scattering is not capable of matching the points as shown by the scattered intensity and polarization curves in fig . 8 ( see caption for details ) . it has not so far been possible to find a single size distribution which would explain the consistent polarization value over a wide wavelength range and the similar variation in scattered flux with scattering angle from j - k ( see fig . to explain the consistency of the polarization , other suggestions involving a grain size distribution together with optical depth effects which ` tune ' the scattering properties with wavelength must be invoked . three possibilities are suggested to explain the dust scattering structure in the homunculus : + a ) the grains possess a range in size which is similar at all positions within the nebula but the extinction of this grain distribution at a given wavelength is such that the particles which contribute most to the scattering have lowest extinction . in other words when the extinction cross section is low , the scattering cross section is high . from mie theory this is not possible for a single grain species but could occur for some grain mixture . the extinction acts to fine tune the size range contributing to scattering . it is assumed here that the scattering angle changes rather little with wavelength ( hence extinction ) . for the polarization to stay constant with wavelength , there would need to be a grain size distribution inside small clumps . the unit optical depth scattering surface would then be deeper at longer wavelengths on account of the lower extinction . grain - gas or grain - grain collisions in the high velocity clouds could perhaps explain the size distribution which would affect the surface regions more strongly ; + b ) the effective scattering angle alters with wavelength on account of the differing extinction . to longer wavelengths the small dust globules become more transparent , resulting in an increase in scattering angle and a greater proportion of the scattered flux arises from towards the rearside of the lobes . this could compensate the increase of polarization with wavelength by providing less polarized flux . whilst this could work for the nw lobe it is not easily able to explain the polarization behaviour in the se lobe . here the scattering angle increases with increasing penetration ( lower line - of - sight extinction ) into the lobe and so the polarization should be expected to increase with increasing wavelength . in this case the relevant parameter is again the line of sight extinction but it affects the scattering angle ; + c ) the grains are aligned by the macroscopic velocity field of the homunculus such that it is their alignment that controls the polarization rather than the individual grains . a rather extreme alignment such as strings of dust particles would be required so it would be the incident radiation on a grain rather than its intrinsic scattering properties which would have a greater effect . given that there are highly collimated ejecta observed outside the homunculus ( weis & duschl @xcite and morse et al . @xcite ) , and that such features appear to extend inwards towards @xmath0 carinae , the suggestion of an influence of the macroscopic grain alignment on the scattered radiation may not be completely ruled out . suggestion ( c ) finds support in the detection of 12.5@xmath3 m polarization by aitken et al . ( @xcite ) , who first showed that there is organized grain alignment in the homunculus . the maximum values of 12.5@xmath3 m polarization were about 5% and the e - vectors are oriented mostly radially at the edges ( aitken et al . @xcite , fig . 2 ) , although the pattern is complex . it is notable that the 12.5@xmath3 m polarization is largest in each lobe where the near - ir polarization is greatest - viz . at the ends of the lobes this suggests an intrinsic connection between the grains at the two wavelengths , rather than the polarization arising in different grain groups at the different wavelengths . aitken et al . ( @xcite ) discuss radiation streaming as a mechanism to provide suprathermal grain spin of paramagnetic grains which then precess about the magnetic field direction . fields strengths upto milli - gauss were suggested and the field orientation in the lobes orthogonal to the major axis was favoured ( aitken et al . one possible scenario which could relate the presence of aligned grains and the constancy of optical - ir polarization with wavelength has the grains in the foreground lobes of the homunculus acting as the aligning medium for the scattered light from the rearside . by comparison with the case of galactic grain alignment , the amount of extinction to produce 30% polarization ( v band ) is e@xmath20 @xmath213.3 ( see e.g. whittet , @xcite , fig . this is a large extinction but not ruled out given the deduced extinction of a few magnitudes for the ` dark ' regions of the homunculus ( see table 2 ) . in addition the grains in the homunculus are probably very different from those in the general interstellar medium , having been recently ejected from a star with anomalous abundances . it is clear that grain alignment can not be wholly responsible for the constancy of the polarization with wavelength but may be a contributor . further observations to explore the polarization in the 3 - 5@xmath3 m region where there is a mixture of scattering and emission would be particularly valuable . the first high spatial resolution adaptive optics near - ir polarization maps of @xmath0 carinae and the homunculus nebula have been presented . since the homunculus is dominated by scattering then the appearance in the near - ir is rather similar to that observed in the optical and a comparison of the ao results with an hst 1.04@xmath3 m wfpc2 image was presented showing essentially the same features . the most important single result from this work is the overall similarity of the linear polarization from the v band to 2.2@xmath3 m within a few percent for the se lobe and the lower values at j and h compared with v for the nw lobe . image restoration was applied to a set of 2.15@xmath3 m continuum images to determine the polarization distribution in the near vicinity of @xmath0 carinae . a tentative value of the polarization of the weigelt et al . speckle knot d of 18% was determined suggesting that it is a dust cloud within the equatorial disc strongly illuminated by @xmath0 carinae . various models are discussed in order to explain the flat distribution of polarization with wavelength over the homunculus . a possible association of a narrow feature within the nw lobe of the homunculus with one of the highly collimated emission line ` whiskers ' outside the nebula deserves further investigation . ageorges n. , walsh j. r. , 1999 , a&as 138 , 163 aitken d. k. , smith c. h. , moore t. j. t. , roche p. f. , 1995 , mnras 273 , 359 allen d. a. , 1989 , mnras , 241 , 95 altamore a. , maillard j .- p . , viotti r. , 1994 , a&a 292 , 208 bensammar s. , letourneur n. , perrier f. , friedjung m. , viotti r. , 1985 , a&a 146 , l1 beuzit j .- l . , demailly l. , gendron e. , et al . , 1997 , exp . astr . 7 , 285 carty t. f. , warren - smith r. f. , scarrott s. m. , 1979 , mnras 187 , 761 currie d. g. , dowling d. m. , shaya e. j. , et al . , 1996 , aj 112 , 1115 daminelli a. , conti p. s. , looes d. f. , 1997 , new a 2 , 107 davidson k. , humphreys r. m. , 1997 , ara&a 35 , 1 davidson k. , dufour r. j. , walborn n. r. , gull t. r. , 1986 , apj 305 , 867 davidson k. , ebbets d. c. , weigelt g. , et al . , 1995 , aj 109 , 1784 davidson k. , ebbets d. c. , johansson s. , et al . , 1997 , aj 113 , 335 apj 305 , 867 davidson k. , gull t. r. , humphreys r , m. , et al . , 1999 , aj 118 , 1777 devillard n. , 1997 , eso messenger 87 , 19 draine b. t. , 1985 , apjs 57 , 587 ebbets , d. c. , garner , h. , white , r. l. , et al . , 1994 , in proc . 34th herstmonceux conference `` circumstellar media in the late stages of stellar evolution '' , eds . r. e. s. clegg , stevens , i. r. , meikle , w. p. s. , cup , p.95 falcke h. , davidson k. , hofmann k .- h . , weigelt g. , 1996 , a&a 306 , l17 gehring , g. , 1992 , unpublished ph . d. thesis , ludwig - maximilians universitt , munich , germany hofmann k .- h . , weigelt g. , 1988 , a&a 203 , l21 hofmann r. , brandl , b. , eckart , a. , et al . , 1995 , proc . spie 2475 , 192 howarth i. d. , 1983 , mnras 203 , 301 humphreys r. m. , davidson k. , 1994 , pasp 106 , 1024 hyland a. r. , robinson g. , mitchell r. m , thomas j. a. , becklin , e. e. , 1979 , apj 233 , 145 jeffries s. m. , christou j. c. , 1993 , apj 415 , 862 koornneef j. , 1983 , a&a 128 , 84 lucy l. b. , 1974 , aj 79 , 745 meaburn j. , walsh j. r. , wolstencroft r. d. , 1993 , a&a 268 , 283 mitchell r. m. , robinson g. , 1978 , apj 220 , 841 morse j. a. , davidson k. , bally j. , et al . , 1998 , aj 116 , 2443 rigaut f. , gehring g. , 1995 , rev . mex . a&a 2 , 27 robinson g. , mitchell r. m. , aitken d. k. , briggs g. p. , roche r. f. , 1987 , mnras 227 , 535 schulte - ladbeck r. , pasquali a. , clampin m. , et al . , 1999 , aj 118 , 1320 seaton m. j. , 1979 , mnras 187 , 75p smith c. h. , aitken d. k. , moore t. j. t. , et al . , 1995 , mnras 273 , 354 smith n. , gehrz r. d. , krautter j. , 1998 , aj 116 , 1332 thackeray a. d. , 1956 , observatory 76 , 154 turnshek d. a. , bohlin r. c. , williamson r. l. , lupie o. l. , koornneef j. , 1990 , aj 99 , 1243 van genderen a. m. , de groot m. j. h. , th p. s. , 1994 , a&a 283 , 89 visvanathan n. , 1967 , mnras 135 , 275 walborn n. r. , liller m. h. , 1977 , apj 211 , 181 warren - smith r. f. , scarrott s. m. , murdin p. , bingham r. g. , 1979 , mnras 189 , 299 weigelt g. , ebersberger j. , 1986 , a&a 163 , l5 weis k. , duschl w. , 1999 , a&a 349 , 467 wesselink g. , 1960 , lowell obs . bull 105 , 305 westphal j. a. , neugebauer g. , 1969 , apj 156 , l45 whitelock p. a. , feast m. w. , carter b. s. , roberts g. , glass i. s. , 1983 , mnras 203 , 385 whitelock p. a. , feast m. w. , koen c. , roberts g. , carter b. s. , 1994 , mnras 270 , 364 whittet d. c. b. , 1992 , _ dust in the galactic environment _ , institute of physics , bristol
high resolution near - infrared adaptive optics imaging and polarimetry have been obtained of the homunculus nebula and its central illuminating star @xmath0 carinae ( hd 93308 ) . images and maps of the linear polarization at a resolution of @xmath10.2@xmath2 have been made in the j , h and k bands and in a narrow 2.15@xmath3 m continuum band ( k@xmath4 ) . the overall appearance of the nebula in the near - ir is similar in all bands and to that at v , with specific features less sharp to longer wavelengths . a comparison between the published hst wfpc2 1.042@xmath3 m map and the ao j band image demonstrates that ground - based ao resolution can approach that of hst . the large - scale pattern of polarization vectors is centro - symmetric demonstrating that single scattering dominates everywhere except perhaps in the central bright core . the only difference between the near - ir and optical appearance is a narrow linear feature at position angle 320@xmath5 extending across the nw lobe of the homunculus . polarization maps at k@xmath4 in the near vicinity of @xmath0 carinae were restored using a psf derived from blind deconvolution . there is a definitely detected extension in the direction of the optically visible speckle knots and an estimate of 18% for the polarization of one of the knots was made . this level of polarization suggests that the knots arise in dust+gas clouds in the near environment of @xmath0 carinae , perhaps in an equatorial disc . the most remarkable result of the linear polarization mapping is the level of similarity in the spatial structure , and also in the degree of linear polarization , between the near - ir and optical data . comparison of the polarization along the projected major axis of the homunculus shows values in the se lobe to within a few percent from v band to 2.2@xmath3 m . in the nw lobe the near - ir linear polarization values agree to within a few percent over the 1.2 - 2.2@xmath3 m range , but are upto 10% lower than at v. such a polarization pattern can not arise in mie scattering from a single power law distribution of grain sizes unless the particles are very small compared with the wavelength , in disagreement with mid - ir observations . in addition the colour dependence of the extinction was found to be shallower than the typical ism , indicating the presence of large grains . several possibilities are explored to try to explain these contradictory results . optical depth effects and a broad distribution in grain sizes are favoured , perhaps with a dependence of the grain size with depth into the small obscuring clouds in the lobes of the homunculus . however the presence of aligned grains , previously inferred from mid - ir polarization , may also affect the scattered radiation from the dust .
mechanico - chemical bond to enamel and dentin is a distinguished characteristic of this cement . fast application and gradual fluoride release have made this element one of the most commonly used materials in pediatric dentistry . to establish an effective adhesion , have reported that the goal of conditioning is to eliminate smear layer and surface contamination that can reduce the cement 's adhesion to the tooth surface , particularity dentinal surfaces . it has been shown that the conditioners concentration and method and time of application can affect smear layer removal . it has also been stated that the acidic nature of glass ionomer cements can partially dissolve the smear layer . el - askary and nassif and glasspoole et al . stated that conditioning of the tooth surface can increase the bond strength of the glass ionomer and lead to better adhesion to the dental hard tissue . at first , it was believed that smear layer should be preserved to protect the pulp from toxic stimuli and reduce outward tubular flow . while using highly concentrated cements , however , today it has been emphasized that smear layer does not provide a stable substrate for adhesion and bonding of the restorative material to the tooth surface . gradually , this layer dissolves under restorative material as a result of hydrolysis process and results in microleakage , bacterial penetration and pulpal inflammation . therefore , the smear layer should be either modified or completely dissolved and removed . since little research has been carried out concerning the effects of different conditioning agents on conventional glass ionomer with high - viscosity bond to the tooth structure and most of them have focused on studying the bond strength , especially in the permanent teeth and no study has compared the effects of these four conditioners ( 20% acrylic acid , 35% phosphoric acid , 12% citric acid , 17% ethylenediaminetetraacetic acid [ edta ] ) , this study was designed to investigate the microleakage of high - viscosity glass ionomer restorations in deciduous teeth after conditioning with four different conditioners . in this in vitro experimental study , 50 intact primary canines with no caries , restorations , fractures or cracks with root resorption of < 1/2 root length , that were extracted due to orthodontic interventions , were collected from pediatric dentists private offices in a 6-month period and kept in 12% thymol solution at room temperature . the remnant soft tissues were removed from the dental surfaces using a scalpel ; then , they were cleaned by brush and low - speed handpiece and water . standard class v cavities were prepared by one operator on all buccal tooth surfaces using sharp diamond flat fissure bur ( kavan 0/135/008 , iran ) and high - speed rotary instrument ( nsk , japan ) with water spray . the cavity dimensions were : 2 mm incisogingival length and 1.5 mm depth and 3 mm mesiodistal width . in all cavities , 1 mm of the cavity length was above and 1 mm of it was beneath cementum - enamel junction . later , the specimen were randomly divided into five groups , each including ten teeth . in the first group ( control group ) , after cavity preparation , rinsing and drying , a cotton pellet was placed in the cavity to avoid complete dehydration of the tooth , then the cotton was removed and the capsulated high - viscosity conventional glass ionomer ( equia , fuji ix gp extra , gc dental co. , tokyo , japan ) was placed in the cavities according to the manufacture 's recommendations ( trituration was for 10 s at 4200 cpm ) using its special applier . in the second group , at first , cavity conditioning was carried out using 20% acrylic acid ( merck kgaa , darmstadt , germany ) for 10 s by micro brushes and rubbing movements . then , cavity was rinsed using water spray for 15 s and water and air spray for another 15 s. after that , a piece of cotton was placed in the cavity and gently dried for 5 s using air spray ; then , the cotton was removed and the cavity was filled by glass ionomer restorative material . in the third , fourth and fifth groups , respectively , all stages were the same as group 2 , except that 35% phosphoric acid gel ( ultra - etch , ultradent productcls inc . , usa ) for 10 s , 12% citric acid ( merck , darmstadt , germany ) for 15 s and edta 17% ( merck , darmstadt , germany ) for 60 s were used as conditioners . after cavity filling , polishing , coating with gc fuji varnish and storing the teeth in distilled water at room temperature for 24 h , the specimens were subjected to thermocycling procedures 500 times at a range of 5 - 55c with an immersion time of 30 s. ( first , 5c 2c , then , room temperature , next , 55c 5c , after that , back to room temperature and finally , 5c 2c ) . after thermocycling , all of the teeth apices were sealed using sticky wax and all the teeth surfaces as well as the mesial and distal margins of the restoration up to 1 mm of the incisal and gingival margins were covered with two layers of nail polish to eliminate any unwanted dye penetration . the specimens were soaked in 2% fuchsin dye solution for 24 h. after removing them from the solution , they were washed with water , the nail polish was removed and each tooth was cut buccolingualy along the tooth 's long axis direction using a diamond disc and cutting machine ( vafain industry , tehran , iran ) , later , each one of the prepared mesial and distal sections was numbered . the amount of microleakage was determined by three individuals separately , using a stereomicroscope with 28 times magnification . for each tooth , marginal leakage classification was based on color penetration in incisal and gingival margins of the restorations as follows : incisal margin ( enamel ) : 0 = no dye penetration in tooth restoration interface.1 = dye penetration in tooth restoration interface which at most has spread to the dentino - enamel junction ( dej).2 = dye penetration in tooth restoration interface which at most has passed dej , but has not reached the axial wall of the cavity.3 = dye penetration in tooth restoration interface which at most has reached the axial wall of the cavity.4 = lateral dye penetration in enamel that has reached the dentin . 0 = no dye penetration in tooth restoration interface . 1 = dye penetration in tooth restoration interface which at most has spread to the dentino - enamel junction ( dej ) . 2 = dye penetration in tooth restoration interface which at most has passed dej , but has not reached the axial wall of the cavity . 3 = dye penetration in tooth restoration interface which at most has reached the axial wall of the cavity . 4 = lateral dye penetration in enamel that has reached the dentin . gingival margin ( dentin ) : 0 = no dye penetration in tooth restoration interface.1 = dye penetration in tooth restoration interface which has spread to less than1/2 of the distance to the axial wall.2 = dye penetration in tooth restoration interface which has spread to more than 1/2 of the distance to the axial wall.3 = dye penetration in tooth restoration interface that has reached the axial wall.4 = lateral dye penetration in dentin that has reached the pulp . 0 = no dye penetration in tooth restoration interface . 1 = dye penetration in tooth restoration interface which has spread to less than1/2 of the distance to the axial wall . 2 = dye penetration in tooth restoration interface which has spread to more than 1/2 of the distance to the axial wall . 4 = lateral dye penetration in dentin that has reached the pulp . for statistics , then , considering the number of each specimen , the grades of each group were collected . wallis and mann whitney tests were used to compare the mean microleakage between the five groups . the significance level was set at p < 0.05 . table 1 shows the mean of microleakage in different groups based on incisal or gingival margins . mean microleakage in different groups based on incisal and gingival margins the two - way anova revealed that there was no significant difference between the means of microleakage in incisal ( enamel ) and gingival ( dentin ) margins ( p = 0.34 ) . whitney test showed that there was no significant difference between the microleakage in enamel and dentin margins ( p = 0.4 ) . the two - way anova also showed a significant difference between the means of microleakage in different groups ( p = 0.03 ) , which means the type of the conditioner affects the amount of microleakage . furthermore , the kruskal wallis test confirmed these results and showed that the amount of microleakage was not equal in all five groups ( p = 0.04 ) . figure 2 shows the mean of microleakage in different groups based on the type of the conditioner . the mean of microleakage in edta and acrylic acid groups was significantly less than citric and phosphoric acid groups ( p = 0.04 and p = 0.045 , respectively ) . the citric acid and phosphoric acid groups showed no significant difference regarding the amount of microleakage ( p = 0.33 ) . the amount of microleakage was significantly higher in the control groups compared with other groups ( p = 0.045 ) . mechanico - chemical bond to both enamel and dentin is an important feature of the glass ionomer cements . the hydrophilic free carboxyl groups within the cement bond to the dentin and increase the surface wetness in order to make hydrogenic bonds between the two surfaces . a close contact between the dental structure and glass ionomer is required for an effective adhesion . some researchers have reported that conditioning of the dental surfaces increases the glass ionomer 's bond strength and leads to better adhesion to dental hard tissue . different materials such as 5% and 12% citric acid , 10% , 20% and 25% acrylic acid , 17% edta , and 35% phosphoric acid have been used to condition dental surfaces . many researches have shown a decrease in the amount of microleakage and an increase in the bond strength of the glass ionomer to dental surfaces using different conditioners . some researchers believe that the acidic nature of glass ionomer causes partial dissolution of the smear layer ; so , there is no benefit in applying conditioners . the residual dentin 's thickness can be the cause of the conflicting results reported in different studies . this study showed that using conditioners results in significantly lower microleakage compared to the control group ( no conditioner ) ( p < 0.05 ) . this could be due to the elimination of debris , removal of smear layer , enamel rod exposure , partial demineralization and formation of microprosities in the enamel and dentinal surfaces , which results in an increased surface for chemical and microchemical bonding . birkenfeld and schulman have reported that etching the enamel before conventional glass ionomer application leads to formation of an undetectable morphologic unit with enamel and decreases the microleakage . glasspoole et al . showed that using 10% polyacrylic acid for 20 s or 35% phosphoric acid for 15 s on enamel surface results in higher bond strength in fuji ii conventional gi . . showed a decreased microleakage and a close contact at the enamel / restoration interface following the application of different conditioners in cavities filled by fuji ix glass ionomer . in this study , there was a statistically significant difference between microleakages using different conditioners ( p < 0.05 ) and the least amount of microleakage was reported for 20% acrylic acid and 17% edta . many studies have mentioned acrylic acid as an excellent conditioner for increasing the bond strength between dentin and glass ionomer . in his research , powis et al . suggested acrylic acid as the most effective conditioner . this acid has little effect on dental tissues and removes the smear layer and surface contamination without opening the dentinal tubules more than needed . gc - conditioner is also available and recommended by the manufacturer , but it is not included in the package . in an sem study , tanumiharja et al . reported that there was no smear layer in dentinal tubules and fuji ix cement matrix had penetrated into the demineralized dentin following the use of 20% acrylic acid , which was in accordance with the present study . although having neutral ph , edta can dissolve the mineral phase of the dentin without affecting the dentinal proteins . it has been claimed that edta causes slight amounts of demineralization which facilitates penetration to dentin and adhesion to residual minerals without opening the dentinal tubules excessively . studies that have shown an increase in the glass ionomer bond to the tooth tissue following the use of edta are in line with this study . in this study , the mean of microleakage was significantly higher in the 12% citric acid and 35% phosphoric acid groups compared with the acrylic acid and edta groups . in addition to removing smear layer , phosphoric acid also removes a large amount of minerals , which results in a decreased level of surface calcium and phosphorus for adhesion purposes . this feature can be significant , while using resin modified glass ionomers where penetration of hydroxyethylmethacrylate monomer tags into dentinal tubules and collagen network is of a great value for increasing the bond strength . conventional glass ionomers bond to enamel , even with the presence of a smear layer , but surface conditioners have been found to improve the bond strength . in this study , there was not a significant difference between the mean microleakage in enamel or dentinal margins , which could be due to similar mineral composition . within the limitations of this study 20% acrylic acid and 17% edta are suggested to be used for cavity conditioning , which can result in better chemical and micromechanical adhesion .
background : glass ionomer cement is a common material used in pediatric dentistry . the aim of this study was to evaluate the microleakage of high - viscosity glass ionomer restorations in deciduous teeth after conditioning with four different conditioners.materials and methods : fifty intact primary canines were collected . standard class v cavities ( 2 mm 1.5 mm 3 mm ) were prepared by one operator on all buccal tooth surfaces , including both enamel and dentin . the samples were divided into five groups with different conditioners ( no conditioner , 20% acrylic acid , 35% phosphoric acid , 12% citric acid , and 17% ethylenediaminetetraacetic acid [ edta ] ) . two - way anova , kruskal wallis and mann whitney tests were used to compare the means of microleakage between the five groups . the significance level was set at p < 0.05.results:there was no significant difference between the means of microleakage in incisal ( enamel ) and gingival ( dentin ) margins ( p = 0.34 ) . furthermore , there was no significant difference between the means of microleakage in enamel and dentin margins ( p = 0.4 ) . there was a significant difference between the means of microleakage in different groups ( p = 0.03).conclusion : within the limitations of this study , it is suggested that 20% acrylic acid and 17% edta be used for cavity conditioning which can result in better chemical and micromechanical adhesion .
a fractal surface ( or fractal curve ) is a fractal set which is a graph of some continuous function on @xmath0 ( or @xmath1 ) . the method of construction of fractal surfaces ( or fractal curves ) are closely related to the generation of fractal interpolation functions(fif ) . the fifs were introduced by barnsley @xcite in 1986 and after that have been widely studied and used in approximation theory , image compression , computer graphics and modeling of natural surfaces such as rocks , metals , planets , terrains and so on . ( see @xcite . ) + the constructions of fractal surfaces ( such as self - similar , self - affine or non self - affine surfaces ) by ifss or rifss have been studied in many papers ( see @xcite ) . these surfaces are all attractors of some ifss or rifss . in order to ensure the continuity of the surface , some authors in the early days assumed that the interpolation nodes on the boundary are collinear . later malysz @xcite , metzler et al . @xcite , feng et al @xcite and yun @xcite studied the construction of fractal interpolation surfaces on arbitrary data sets using ifs . furthermore , @xcite , @xcite and @xcite estimated the dimensions of the result surfaces . in @xcite , the authors studied the construction of _ recurrent _ fractal interpolation surfaces . in @xcite they use _ constant contraction factors _ in construction of ifs or rifs and in @xcite they use _ function contraction factors _ in construction of ifs . + the fractal properties of such rough surfaces as those of metals or rocks may expressed by sectional profiles of those surfaces . that s why constructions of fractal surfaces by fractal curves have been studied in many papers ( see @xcite ) . in @xcite , mandelbrot suggested that the fractal dimension of a surfaces constructed by a single curve can be obtained by adding 1 to the fractal dimension of the curve . in @xcite , falconer introduced fractal surfaces constructed by the movement of a fractal curve along a segment and determined their fractal dimension . xie et al . @xcite proposed the so called _ star product fractal surfaces _ which are constructed by the movement of a fractal curves along another one . after that @xcite provided a construction of fractal surfaces by 4 fractal curves which are boundary curves of the constructed surface and in @xcite a construction of bush type fractal surfaces by two bush curves were studied . @xcite provided a construction of fractal surfaces by the fractal interpolation . all these constructions of fractal surfaces by fractal curves have common property that the fractal dimension of the constructed surfaces is determined by the fractal dimensions of the fractal curves constructing them and used the fractal curves constructed by ifs or rifs with _ constant contraction factors_. such a constant vertical scaling factors are not consistent with reality @xcite . + we construct recurrent fractal curves by more general rifss with function scaling factors and estimate the box - counting dimension of the constructed curves . and we construct wider class of fractal surfaces by fractal curves and lipschitz functions , and calculate the box - counting dimension of the constructed surfaces . finally we combine both constructions to construct fractal surfaces . + the remainder of the article is organized as follows : the section 2 describes some basic notions of rifs . the section 3 constructs recurrent fractal curves with function vertical scaling factors and estimates their box counting dimensions . the section 4 provides a general method of construction of fractal surfaces combining fractal curves using lipschitz functions and a formula of the box - counting dimensions . as one application of the results of the section 3 and 4 , the section 5 describes a method of constructing fractal surfaces combining the recurrent fractal curves constructed in the section 3 using some lipschitz functions and provides some examples . in this section we describe some basic notions on recurrent iterated function systems and related lemmas . the class of irreducible matrices are important in rifs theory . + + @xcite let @xmath2be @xmath3 matrix . @xmath4 is called _ * reducible * _ , if the set of indices @xmath5 can be decomposed into two distinct and complementary subsets @xmath6 and @xmath7 , i.e. , @xmath8 @xmath9 such that @xmath10 if this is not possible , then @xmath4 is an * _ irreducible _ * matrix . + + the following results on irreducible matrices are useful and readers can refer to @xcite . [ l:1 ] consider an @xmath11 square matrix @xmath12 . the following statements are equivalent . + 1 ) @xmath12 is irreducible . + 2 ) for every pair @xmath13 , there is a @xmath14 such that the element of the @xmath15-th row @xmath16-th column of the matrix @xmath17 is positive . [ l:2 ] @xmath12 is a non - negative , reducible @xmath11 matrix , iff the matrix @xmath18 is positive ( where @xmath19 is the identity matrix ) . [ l:3 ] ( * perron - frobenius theorem * ) let @xmath20 be an irreducible square matrix . then we have the following two statements . + 1 ) the spectral radius @xmath21 of @xmath12 is an eigenvalue of @xmath12 and it has strictly positive eigenvector @xmath22 ( i.e. , @xmath23 for all @xmath15 ) . + 2 ) @xmath24 increases if any element of @xmath12 increases . * definition 2 * @xcite @xmath25 is a complete metric space and @xmath26 are subsets of @xmath27 . let @xmath28 be contraction maps . @xmath29 is a @xmath11 row - stochastic matrix ( i.e. , such a matrix that @xmath30 ) and irreducible . then @xmath31 is called a * _ recurrent iterated functions system _ * ( or simply rifs ) . the @xmath11 matrix @xmath32 defined by @xmath33 is called the * _ connection matrix _ * of rifs . + + let @xmath34 be the set of all nonempty compact subset of @xmath27 and @xmath35 the hausdorff distance in @xmath34 . then @xmath36 is a complete metric space @xcite . in the set @xmath37 , we define a distance @xmath38 as follows : @xmath39 then @xmath40 is a complete metric space @xcite . + for a given recurrent iterated functions system @xmath31 , we define the transformation @xmath41 of @xmath42 as follows : let @xmath43 for every @xmath44 . here @xmath45 . we will denote the transformation @xmath46 as a matrix form by @xmath47 this transformation @xmath46 is a contraction map in @xmath42 and the unique fixed point @xmath48 is called the * _ attractor _ * or * _ invariant set _ * of the rifs , or * _ recurrent fractal _ * @xcite . + + * note*. the invariant _ set _ of rifs is a _ vector _ whose elements are nonempty compact sets . if @xmath48 is the invariant _ set _ of a rifs @xmath31 , then we have @xmath49 . usually , making a slight abuse of notation , we often call the union @xmath50 of all @xmath51 as the attractor of rifs , too . + + * definition 3*. a curve which is the invariant set of a rifs on @xmath52 is called a * _ recurrent fractal curve _ * ( or rfc ) . * definition 4*. in general , the * _ box - counting dimension _ * @xmath53 of a fractal set @xmath54 is defined by @xmath55 ( if this limit exists ) , where @xmath56 is any of the followings ( see @xcite ) : 1 . the smallest number of closed balls of radius @xmath57 that cover @xmath54 ; 2 . the smallest number of cubes of side @xmath57 that cover @xmath54 ; 3 . the number of @xmath57-mesh cubes that intersect @xmath54 ; 4 . the smallest number of sets of diameter at most @xmath57 that cover @xmath54 ; 5 . the largest number of disjoint balls of radius @xmath57 with centers in @xmath54 . here we use ( iii ) . in this section , we construct recurrent fractal curves with function vertical scaling factors and estimate their box - counting dimensions . let a data set be @xmath58 and let @xmath59,~i_i=[x_{i-1}.x_{i}],~i=1,\ldots , n.\ ] ] we denote lipschitz ( or contraction ) constant of lipschitz ( or contraction ) mapping @xmath60 by @xmath61 ( or @xmath62 ) . let @xmath63 and let @xmath64,~x_{s(k)}$],@xmath65 , here @xmath66 . as a custom , @xmath67 is called a _ region _ and @xmath68 a _ domain_. + we collect a map @xmath69 . this means that we relate every region to a domain . for each @xmath70 , let @xmath71 . for @xmath70 ( and @xmath72 ) , let a mapping @xmath73 be such a contraction homeomorphism that @xmath74 . such a map can be easily constructed in a standard way . let @xmath75 be such a sufficiently large interval that @xmath76 . let @xmath77 be a function defined by @xmath78 and satisfy @xmath79 here @xmath80 is a lipschitz function on @xmath81 such that @xmath82 , @xmath83 is a lipschitz function defined on the domain @xmath84 and @xmath85 is a contraction function on @xmath67 with @xmath86 ( which is called a _ * vertical scaling factor * _ ) . + + * example 1*.[exam:1 ] the function @xmath87 satisfying can be easily constructed . when @xmath88 are lipschitz mappings on @xmath89 and satisfy the conditions @xmath90 and @xmath85 are taken as free unknown functions , the functions @xmath91 satisfy . + + we define transformations @xmath92 by @xmath93 [ l:4 ] there exists a distance @xmath94 equivalent to the euclidean metric on @xmath52 such that @xmath95 are contraction transformations with respect to this distance . fix a positice number @xmath96 and define @xmath97 by @xmath98 then @xmath94 is evidently equivalent to the euclidean metric on @xmath52 . in what follows , if we denote maximum value of @xmath99 on its domain by @xmath100 , then for @xmath101 , we have @xmath102|x - x^\prime|+\theta\bar{s}l_a|y - y^\prime|.\end{aligned}\ ] ] here @xmath103 , and similarly , all @xmath104 and @xmath105 ( without indices ) are defined as the maximum of those with indices . note that @xmath106 . if we select @xmath96 so that @xmath107 then all the transformations @xmath108 are contraction maps with contraction constants less than @xmath109 . ( qed ) + we give a _ row - stochastic _ matrix @xmath110 as follows . for every @xmath111 , let @xmath112 be the number of the domains @xmath113 containing the region @xmath67 this means that if we let @xmath114 and @xmath115 for every @xmath116 , then for fixed @xmath117 , @xmath112 is the number of elements of the set @xmath118 . now let @xmath119 then the matrix @xmath120 is the _ connection _ matrix . + let @xmath121 . the attractor of the recurrent iterated functions system(rifs ) @xmath122 @xmath123 is denoted by @xmath54 . then the following theorem shows that @xmath54 is a recurrent fractal curve . [ t:1 ] the attractor @xmath54 constructed above is a graph of some continuous function which interpolates the data set @xmath124 . ( * proof * ) let @xmath125 , then the set @xmath126 is complete metric space with respect to norm @xmath127 . we can easily know that the operator @xmath128 ; @xmath129 is well defined and the operator @xmath130 is a contraction on the complete metric space @xmath126 . therefore the operator @xmath130 has a unique fixed point in @xmath126 , which we denote by @xmath60 . then the @xmath60 is presented by @xmath131 which means that @xmath132 , where @xmath133 denote a graph of @xmath60.(qed ) + + we estimate box - counting dimensions of the recurrent fractal curves constructed above . we can assume that @xmath134 $ ] , since the box - counting dimension is invariant under lipschitz homeomorphisms . for a set @xmath135 or @xmath136 and a function @xmath60 defined on @xmath137 , @xmath138=sup\left\{|f(x_2)-f(x_1)|;x_1,x_2\in d\right\}.\ ] ] is called the _ maximum variation _ of @xmath60 on @xmath137 . + let @xmath89 be a interval in @xmath139 , @xmath140 a contraction homeomorphism , @xmath141 lipschitz mappings and @xmath142 contraction mappings with @xmath143 . we define a mapping @xmath144 by @xmath145 [ l:5 ] let @xmath146 be continuous function . then @xmath147\leq\bar s l_a r_f[i]+|i|(c_s\bar a_f+l_b).\ ] ] here @xmath148 is a length of the interval @xmath89 , @xmath149 and @xmath150 . [ t:2 ] let @xmath54 be the recurrent fractal curve in theorem [ t:1 ] . if there is some interval @xmath165 such that the points of @xmath166 are not collinear , then the box - counting dimension @xmath167 of @xmath54 has the following lower and upper bounds ; + 1 ) if @xmath168 , then @xmath1692 ) if @xmath170 , then @xmath171 where @xmath172 , @xmath173 are respectively spectral radii of the irreducible matrices @xmath174 , @xmath175 . in this section we provide a _ general method _ of construction of fractal surfaces combining fractal curves using lipschitz functions and a formula of the box - counting dimensions . we consider fractal surfaces only on the unit square @xmath254\times\left[0,1\right]$ ] because our results can easily be generalized to any square @xmath255\times\left[c , d\right]$ ] . let denote @xmath256 $ ] and @xmath257 . let @xmath258 be fractal curves ( i.e. @xmath60 and @xmath259 are continuous and their graphs are fractal sets ) . let @xmath260 be continuous lipschitz functions with lipschitz constants @xmath261 and @xmath262 respectively . for @xmath263 , we define a continuous function @xmath264 by @xmath265 the following theorem shows that the graph of this function @xmath266 is a fractal set . [ t:3 ] let the function @xmath266 be given by . then the box - counting dimension @xmath267 @xmath268 of its graph is @xmath269 to prove the theorem , we need some lemmas on box - counting dimension . the following lemma is easily proved from the definition of the box - counting dimension . [ l:6 ] let @xmath54 and @xmath270 be fractal sets and @xmath271 . then @xmath272}{-\log\delta}=\mathrm{dim}_\mathrm{b}\mathcal{a},\nonumber\\ & & \lim_{\delta \to 0}\frac{\log\left[\mathrm{n}_\delta\left(\mathcal{a}\right)+\mathrm{n}_\delta\left(\mathcal{b}\right)\pm \delta^{-1}\right]}{-\log\delta}=\mathrm{dim}_\mathrm{b}\mathcal{a},\nonumber\\ & & \lim_{\delta \to 0}\frac{\log\left[\mathrm{n}_\delta\left(\mathcal{a}\right)\pm \delta^{-1}\right]}{-\log\delta}=\mathrm{dim}_\mathrm{b}\mathcal{a}.\nonumber\end{aligned}\ ] ] [ l:7 ] let the functions @xmath273 be fractal curves . if we define a function @xmath274 by @xmath275 then the box - counting dimension @xmath276 is as follows : @xmath277 ( * proof * ) divide the interval @xmath89 into @xmath278 subintervals with the same length , denote the @xmath15-th subinterval by @xmath279 $ ] and denote @xmath280 . in the calculation of the box - counting dimension , we use @xmath281-mesh cubes of @xmath282 for @xmath283 . in a fixed @xmath281-mesh of @xmath282 , let denote the set of all @xmath281-mesh cubes that intersect a set @xmath12 by @xmath284 . let @xmath285 be the number of elements of @xmath286 . similarly , in the @xmath281-mesh of @xmath287 consisting of @xmath288s , let denote the set of all @xmath281-mesh squares that intersect the graph @xmath133 of @xmath60 by @xmath289 and let @xmath290 be the number of elements of @xmath291 . evidently for any @xmath292 we have @xmath293=\mathrm{r}_f\left[\mathrm{i}_i\right]+\mathrm{r}_g\left[\mathrm{i}_j\right].\ ] ] on the other hand , let @xmath294\cdot\left(\frac{1}{n}\right)^{-1}-\left[r_{f^\prime}[e_{ij}]\cdot\left(\frac{1}{n}\right)^{-1}\right]$ ] . here @xmath295 $ ] is the integer part of @xmath296 and @xmath297 . if @xmath298 , then @xmath299\cdot\left(\frac{1}{n}\right)^{-1}=\left[r_{f^\prime}[e_{ij}]\cdot\left(\frac{1}{n}\right)^{-1}\right]\leq n_{1/n}^{ij}(gr(f^\prime))\leq \left[r_{f^\prime}[e_{ij}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+1\ ] ] and if @xmath300 , then @xmath299\cdot\left(\frac{1}{n}\right)^{-1}=\left[r_{f^\prime}[e_{ij}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+v\leq n_{1/n}^{ij}(gr(f^\prime))\leq \left[r_{f^\prime}[e_{ij}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+2.\ ] ] therefore we have @xmath301\cdot\left(\frac{1}{n}\right)^{-1}\right]\leq n^{ij}_{1/n}(gr(f^\prime))\leq \left[r_{f^\prime}[e_{ij}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+2.\end{aligned}\ ] ] similarly we have @xmath302\cdot\left(\frac{1}{n}\right)^{-1}\right]\leq n^{i}_{1/n}(gr(f))\leq \left[r_{f}[i_{i}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+2,\label{eq:8}\\ % ( 8) \left[r_g[i_{j}]\cdot\left(\frac{1}{n}\right)^{-1}\right]\leq n^{j}_{1/n}(gr(g))\leq \left[r_{g}[i_{j}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+2 . \label{eq:9 } % ( 9)\end{aligned}\ ] ] on the other hand , noting that for any real numbers @xmath303 we have @xmath304+[n]\leq [ m+n]\leq [ m]+[n]+1 $ ] , from , , and , we have @xmath305\cdot\left(\frac{1}{n}\right)^{-1}\right]+\left[r_g[i_{j}]\cdot\left(\frac{1}{n}\right)^{-1}\right]\leq n^{ij}_{1/n}(gr(f^\prime))\leq \left[r_f[i_{i}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+\left[r_g[i_{j}]\cdot\left(\frac{1}{n}\right)^{-1}\right]+3.\ ] ] therefore @xmath306 thus we have @xmath307 from lemma [ l:6 ] and the definition of the box - counting dimension we get the result . ( qed ) [ l:8 ] let the functions @xmath308 be the same as the above ones . if we define the function @xmath309 by @xmath310 , then the box - counting dimension @xmath311 is the same as that of the function @xmath60 . ( * proof * ) for any @xmath312 , @xmath313 let denote @xmath314 and @xmath315 . we can suppose @xmath316 ( see remark 2 ) . then , for @xmath278 large enough , @xmath317 @xmath318-\mathrm{l}_\lambda\frac{1}{n}\mathrm{m}_f \leq \mathrm{r}_{\lambda f}\left[{i}_i\right]\leq c_{\lambda_2}\mathrm{r}_f\left[{i}_i\right]+\mathrm{l}_\lambda\frac{1}{n}\mathrm{m}_f.\nonumber\end{aligned}\ ] ] thus @xmath319 where @xmath320 , @xmath321 . taking logarithms , the definition of the box - counting dimension and lemma 1 give the result . ( qed ) + + * remark 2 * in the case where @xmath322 , we choose @xmath323 such that @xmath324 and define a function @xmath325 by @xmath326 for @xmath327 . then @xmath328 therefore , from lemma [ l:6 ] and lemma [ l:7 ] , we have @xmath329 . + + ( * proof of theorem 3 * ) lemma [ l:7 ] and lemma [ l:8 ] give the result of the theorem . ( qed ) [ corollary1 ] let @xmath330 be fractal curves and @xmath331 be ( one - variable ) lipschitz functions for @xmath332 . then the box - counting dimension @xmath333 of the function @xmath264 defined for @xmath334 by @xmath335 is as follows : @xmath336 the following theorem can be proved by the same method with the theorem [ t:3 ] . [ gen ] let @xmath330 be the same as in theorem [ t:3 ] and @xmath337 bivariate lipschitz functions for @xmath332 . then the function @xmath264 defined for @xmath263 by @xmath338 has the box - counting dimension of @xmath336 * remark 3 * the fractal surfaces provided in @xcite are contained in the family of fractal surfaces defined by and . as a simple application of the results of the preceding 2 sections , we can easily construct fractal surfaces if we use at least 2 recurrent fractal interpolation curves . this methods can have wide applications . for one example , if data sets are given along the ( x- and y- ) boundaries ( or several parallel lines to the boundaries ) of a square , we can construct the fractal surfaces interpolating the data sets on the boundaries ( or the parallel lines to the boundaries ) by control of @xmath339 and @xmath340 in . the results of the calculations of the box - counting dimension in section 4 show that the complexity of the fractal surfaces defined above are dominated by the fractal curves generating them . thus , the more flexible a construction of fractal curves is , the more natural the fractal surface constructed by them is . we can control the complexity and shape of the fractal surfaces constructed in section 4 in our own way by the vertical contractive function @xmath341 , the stochastic matrix @xmath124 and lipschitz functions @xmath342 used in construction of recurrent fractal curves in section 3 and the control lipschitz functions @xmath343 and @xmath344 used in construction of fractal surfaces by combining fractal curves in section 4 . so , the fractal surfaces presented in this paper could be more appropriate to model natural objects . + + * example 2*. construction of rfc and fs by rfc . the figure [ fig1 ] and figure [ fig2 ] show the recurrent fractal curves generated from data set @xmath345 , @xmath346 using the method of the example 1 on page with different vertical scaling factor functions , where we use linear transformations @xmath347 and interpolation polinomials @xmath259 and @xmath35 . the figure [ fig3 ] and figure [ fig4 ] show the fractal surfaces constructed using recurrent fractal curves and different lipschitz functions . the recurrent fractal curves @xmath348 and @xmath349 are constructed by the method of the section 3 . here the vertical scaling factor of @xmath348 is @xmath350 and the vertical scaling factor of @xmath349 is @xmath351\cdot 0.5 $ ] . in the figure [ fig3 ] , we used the lipschitz functions @xmath352 in a ) and @xmath353 in b ) . in the figure [ fig4 ] , we used the lipschitz functions @xmath354 in c ) and @xmath355 in d ) . 99 barnsley m.f . , fractals everywhere . academic press , new york ; 1988 . barnsley m.f . , _ fractal functions and interpolation_. constr . approx . 1986;*2*:2303 - 329 . http://link.springer.com/article/10.1007/bf01893434#page-2[cross-ref ] bouboulis p. , dalla l. , _ fractal interpolation surfaces derived from fractal interpolation functions_. j. math . 2007;*336*:919 - 936 . http://dx.doi.org/10.1016/j.jmaa.2007.01.112[doi : 10.1016/j.jmaa.2007.01.112 ] bouboulis p , dalla l and drakopoulos v. , _ construction of recurrent bivariate fractal interpolation surfaces and computation of their box - counting dimension_. j. approx . theory , 2006;*141*:99 - 117 . http://dx.doi.org/10.1016/j.jat.2006.01.006[doi:10.1016/j.jat.2006.01.006 ] feng , z.g . ; feng , y.z . and yuan , z.y.;_fractal interpolation surfaces with function vertical scaling factors _ , applied mathematics letters , 2012 , * 25 * , 1896 - 1900 . http://dx.doi.org/10.1016/j.aml.2012.02.059[doi:10.1016/j.aml.2012.02.059 ] malysz r. , _ the minkowski dimension of the bivariate fractal interpolation surfaces_. chaos , solutions and fractals , 2006;*27*:1147 - 1156 . http://dx.doi.org/10.1016/j.chaos.2005.05.007[doi:10.1016/j.chaos.2005.05.007 ] metzler w , yun c.h . , _ construction of fractal interpolation surfaces on rectangular grids _ , j. bifurcation and chaos , 2010 ; * 20 * , 4079 - 4086 . http://dx.doi.org/10.1142/s0218127410027933[doi:10.1142/s0218127410027933 ] xie h.p . , feng z.g . and chen z.d . , _ on star product fractal surfaces and their dimensions _ , applied mathematics and mechanics , 1999;*20(11)*:1183 - 1189 . http://dx.doi.org/10.1142/s0218127410027933[doi : 10.1142/s0218127410027933 ] yun , chol - hui ; _ box - counting dimension of a kind of fractal interpolation surface on rectangular grids _ , romanian journal of mathematics and computer science , http://www.rjm-cs.ro/yun2012.pdf[2012,vol.*6 * , issue * 4 * , 61 - 69 ] , arxiv preprint : http://arxiv.org / abs/1208.2081[arxiv:1208.2081[math.ds ] ] yun , chol - hui ; metzler , w. and barski , m.;_image compression predicated on recurrent iterated function systems _ , @xmath360 international conference on mathematics and statistics , 16 - 19 june , 2008 , athens , greece , pages 1 - 11 , arxiv preprint : http://arxiv.org / abs/1304.2014[arxiv:1304.2014[math.ds ] ]
a method to construct fractal surfaces by recurrent fractal curves is provided . first we construct fractal interpolation curves using a recurrent iterated functions system(rifs ) with function scaling factors and estimate their box - counting dimension . then we present a method of construction of wider class of fractal surfaces by fractal curves and lipschitz functions and calculate the box - counting dimension of the constructed surfaces . finally , we combine both methods to give more flexible constructions of fractal surfaces . + + + * 2010 _ mathematical subject classification _ * : 37c45 ; 28a80 ; 41a05
it is estimated that about 22 percent of iranian couples have primary infertility problems ( 1 ) . infertility is the inability of a couple to achieve conception after a year or more of regular unprotected intercourse ( 2 ) . many studies have documented that couples with infertility problems experience mental health problems such as distress , anxiety and depression . one of the most common mental health problems among women with infertility problems is depression ( 3 , 4 ) . research has found that 21% of couples with fertility problems experienced clinical depression ( 5 ) . studies on the prevalence of depression among iranian couples with infertility have reported various statistics from 5 to 50 percent ( 68 ) . previous research has found that several factors including the age , education , social support and the pressure of husband s family for pregnancy influence infertile couples mental health . within traditional societies such as iran , women are expected to give birth and families blame them if they can not give birth so , they are more under the mental pressure compared with men ( 9 ) . religious coping refers to the use of religious beliefs or practices to cope with stressful life situations ( 10 ) . research has shown that religious beliefs and practices can help people to cope with difficult situations such as physical illnesses ( 11 ) , stress and depression ( 1214 ) . individuals who use religious coping appear to handle their conditions more effectively than those who do not ( 15 ) . religion is often involved in the reconstruction of traumatic events and provides a framework for understanding the most senseless accident , the most unbearable pain , or the most unjust outcome ( 16 ) . if one relies on a higher power , one feels less pressure to control circumstances and to worry about results ( 17 ) . this way of appraising a stressful life situation may relieve anxiety and counteract feelings of hopelessness and despair , even in the most desperate circumstance ( 18 ) . studies have indicated that people with higher level of religiosity use religious beliefs and practice strategies more frequently than other ways of coping . many studies have reported a positive relation between use of religious coping and physical / mental health ( 19 ) . for example , research has examined the reactions of victims of chronic illnesses , and found that the most common explanation for the event was to view it as part of god s plan ( 10 ) . furthermore , pargament also found that in several health - related situations , causal attributions to god were greater than to any other sources ( 20 ) . the surveys have shown that religion and spirituality are significant for the majority of iranian people ( 21 ) . a relatively large proportion of iranian couples with infertility experience psychological distress ( 22 , 23 ) . the majority of studies in iran on the relation between religiosity and mental health have reported the positive impact of religious beliefs and practice on mental health . research conducted in iran so far has used a general measure of religiosity to assess religious coping . it is important to explore the types of religious beliefs that women use for coping with such stressful situations as infertility . the present study tried to use a multi - dimension scale to assess different ways of religious coping . the various forms of religious coping have had different implications for adjustment to major life events . more specifically , the purpose of this study was to explore the role of different religious coping strategies in predicting depression in a group of women with fertility problems in shiraz . this study was a correlational one in which the components of religious coping ( practice religious , active religious coping , passive religious coping , benevolent reappraisal and negative religious coping ) were considered as independent variables and depression was considered as dependent variable . a total of 72 women with fertility problems seeking treatment were recruited for this study from several private infertility clinics in shiraz using convenience sampling . all participants gave consent to participate in this study and they were assured of anonymity and confidentiality . the criteria for entering into the study included the inability to achieve conception despite unprotected sexual intercourse of at least 1 year confirmed by a gynecologist and the ability to understand the questionnaires . descriptive statistics ( frequency percentage , mean and standard deviation ) , pearson s correlation and simultaneous multiple regression analysis were used for data analysis using spss version 16 . the beck depression inventory ( bdi - ii ) is the most commonly used screening instrument for measuring depression in the general population . the bdi - ii ( 24 ) is a 21-item self - report instrument designed to measure severity of depression . each item is rated on a 4-point scale ranging from 0 ( never ) to 3 ( often ) . the ratings are summed , yielding a total score that can range between 063 ( 09 minimal depression , 1018 mild depression , 1929 moderate depression , 3063 severe depression ) . studies carried out in iran have used this scale and reported a good reliability and validity for that . this research has reported a cronbach s alpha coefficient of 0.85 for this scale ( 26 ) . religious coping scale is used to assess religious beliefs and practice strategies within islamic context ( 27 ) . this scale consists of 21 items and five dimensions including practice religious coping ( 6 items e.g . , i sought help with prayer ) , benevolent reappraisal religious coping ( 6 items e.g . , i saw my situation as god s will ) , active religious coping ( 3 items e.g . , i turned the situation over to god after doing all that i could ) , passive religious coping ( 3 items e.g . , i did nt do much , just expected god to solve my problems for me ) and negative religious coping ( 4 items e.g . the participants answered the items on a 5 likert scale ranging from 0 ( not at all ) to four ( a great deal ) . higher score on this measure indicates frequent use of religious beliefs and a lower score indicates infrequent use of religious coping . this scale has been utilized in iran and has been found to have a good reliability and validity . the internal consistency of the scale using cronbach s alpha has been reported 0.89 for practice , 0.79 for negative , 0.82 for benevolent , 0.72 for passive and 0.78 for active religious coping . the beck depression inventory ( bdi - ii ) is the most commonly used screening instrument for measuring depression in the general population . the bdi - ii ( 24 ) is a 21-item self - report instrument designed to measure severity of depression . each item is rated on a 4-point scale ranging from 0 ( never ) to 3 ( often ) . the ratings are summed , yielding a total score that can range between 063 ( 09 minimal depression , 1018 mild depression , 1929 moderate depression , 3063 severe depression ) . studies carried out in iran have used this scale and reported a good reliability and validity for that . this research has reported a cronbach s alpha coefficient of 0.85 for this scale ( 26 ) . religious coping scale is used to assess religious beliefs and practice strategies within islamic context ( 27 ) . this scale consists of 21 items and five dimensions including practice religious coping ( 6 items e.g . , i sought help with prayer ) , benevolent reappraisal religious coping ( 6 items e.g . , i saw my situation as god s will ) , active religious coping ( 3 items e.g . , i turned the situation over to god after doing all that i could ) , passive religious coping ( 3 items e.g . , i did nt do much , just expected god to solve my problems for me ) and negative religious coping ( 4 items e.g . the participants answered the items on a 5 likert scale ranging from 0 ( not at all ) to four ( a great deal ) . higher score on this measure indicates frequent use of religious beliefs and a lower score indicates infrequent use of religious coping . this scale has been utilized in iran and has been found to have a good reliability and validity . the internal consistency of the scale using cronbach s alpha has been reported 0.89 for practice , 0.79 for negative , 0.82 for benevolent , 0.72 for passive and 0.78 for active religious coping . the average age of the participants was 31.60 years ( sd=5.35 ) . the education level for the sample was : below high school ( 24% ) , high school ( 49.3% ) , undergraduate ( 22.6% ) , and postgraduate ( 3% ) furthermore , the average time from diagnosis to treatment was 3.41 years ( sd=0.85 ) . thirty percent of the participants scored above the cutoff point on the bdi scale and met the criteria for clinical depression . fifty six individuals fell on minimal depression range ; sixteen persons fell on mild depression range ; six individuals fell on moderate depression range , and no one had severe depression . with regards to religious coping , positive patterns of religious coping were used more frequently than the negative patterns by women with infertility problems . the most commonly used religious coping strategies were practice religious coping ( mean=3.05 , sd=0.73 ) and active religious coping ( mean=2.87 , sd=0.88 ) , while the least commonly used strategies were passive religious coping ( mean=1.52 , sd=1.04 ) and negative religious coping ( mean=1.88 , sd=0.49 ) . furthermore , simultaneous multiple regression was used to assess the prediction of depression based on religious coping dimensions . preliminary analyses were conducted to ensure no violation of the assumption of normally , multicollinearity , and homoscedasticity . the regression analysis showed that active religious coping ( =0.33 , p<0.01 ) , practice religious coping ( =0.32 , p<0.01 ) and benevolent reappraisal religious coping ( =0.34 , p<0.01 ) negatively predicted depression . all the independent variables ( benevolent reappraisal , active , practice , negative and passive religious coping ) explained 32 percent of the total variance of depression . furthermore , women using religious practices for coping with their stressful conditions were less likely to experience the symptoms of depression and those with benevolent beliefs were less likely to suffer from depression . demographics characteristics for sample ( n=72 ) means and standard deviations of religious coping scales predicting depression based on different dimensions of religious coping dependent variable : depression the present study showed that about 30% of women with infertility problems met criteria for depression . these women used practice religious coping more frequently than the other types of religious coping strategies . they also used negative and passive religious coping strategies less frequently than positive religious coping methods . these results are in agreement with literature that suggests the use of religious coping can help people under stress to manage their distress ( 28 ) . these results support pargamen s conceptualization of religious coping that indicates religion as an important philosophical orientation influencing the understanding of the world , and making reality and sufferings understandable and bearable ( 29 ) . this study also demonstrated that benevolent reappraisal , practice and active religious coping strategies predicted the lower rates of depression . these findings are in agreement with literature showing the different types of religious coping in relation with increased or decreased depression ( 30 , 31 ) . with regard to the impact of benevolent reappraisal , the participants might redefine their stressful situation as an opportunity for spiritual growth and see their infertility as god s will or as god s trail ( 15 , 20 ) . the findings of this study on benevolent reappraisal support previous research indicating that religion facilitates the perception of positive aspects of stressful situations ( 32 ) . to the extent that religious people believe that their lives are controlled by a higher power or that negative life events happen for a reason or that life events are opportunities for spiritual growth , they may experience life events as less threatening and less stressful ( 33 ) . as a result , these positive appraisals may help to protect some religious individuals from depressive symptoms by helping them to perceive negative events as less stressful . this study revealed that women who actively tried to overcome their problems and then turned their situation to god were less likely to experience depression . it was found that active religious coping helped infertile women to adjust with their situation . indeed , by using active coping , people take the required action and leave the results to god . the findings that active religious coping were associated with decreased depression is similar to that of koenig s study on religious coping and depression ( 34 ) . it is argued that religious practices such as praying can help couples to cope with their stressful conditions . difficult situations such as infertility may encourage individuals to use religious coping strategies to adapt to their conditions . these results support the notion that there is a unique relation between positive religious coping methods and depression reduction ( 30 ) . furthermore , people who feel the most desperate may be more likely to turn to religion ; that is , high levels of depression may precede increased use of religious coping ( 12 , 35 ) . this study suggests that individuals who use religious coping are able to view infertility as an opportunity for positive growth and that this has a positive effect on psychological well - being ( 27 ) . second , this study used cross - sectional design , so future research should use a longitudinal design . finally , this study investigated only women who were seeking treatment , whereas , a number of couples may not seek treatment , and a more general population should be included in the next studies . the present study provides more support for the impact of religious coping strategies on mental health and also offers significant directions for future studies . it can help health system to include religiosity and spirituality into intervention programs to promote the mental health of couples with fertility problems . the present study highlights the importance of religious beliefs and practice to protect women with infertility against depression . this finding showed that the greater use of religious coping was associated with lower levels of depression ; thus , they can help professionals to consider religious coping for treatment interventions .
background : one of the most common mental health problems among women with infertility problems is depression . research has shown that religious beliefs and practices can help people to cope with difficult situations . the purpose of this study was to explore the role of different religious coping strategies in predicting depression in a group of infertile women in shiraz.methods:a total of 72 women with fertility problems were recruited from several private infertility clinics in shiraz using convenience sampling . the participants completed the research questionnaires including beck depression inventory and religious coping scale . the religious coping scale consists of five dimensions including practice , active , passive , benevolent reappraisal and negative religious coping . descriptive statistics ( frequency percentage , mean and standard deviation ) , pearson s correlation and simultaneous multiple regression analysis were used for data analysis using spss version 16 . a p - value less than 0.05 was considered statistically significant.results:the present study showed that about 30% of women with fertility problems experienced the symptoms of depression . the findings also indicated that the most commonly used religious coping strategy was practice religious coping , while the least commonly used religious coping strategies were passive and negative religious coping . the findings also showed that active religious coping , practice religious coping and benevolent reappraisal coping predicted depression reduction.conclusion:this study highlights the effect of religious coping on depression reduction of women with fertility problems . in other words , women who used religious coping strategies were less likely to experience depression symptoms .
type of study and population sample - in this cross - sectional observational study , the total sample was subdivided into two groups : patients affected by leprosy reactions during or after treatment and patients without leprosy reactions at any time . the sample consisted of 440 leprosy patients diagnosed by a committee of leprosy experts based on clinical and laboratory tests and classified according to the clinical presentation and operational classification . data collection - clinical , epidemiological and laboratory data from secondary sources ( medical records ) were gathered using a data collection form that included stratified fields for the allocation of potential risk factors for the occurrence of leprosy reactions during and after treatment . the variables considered were as follows : clinical and operational classification , gender , age , ethnic group , bacterial index ( bi ) , pcr for the detection of m. leprae dna , anti - pgl-1 elisa serology , intradermal mitsuda test results , complete blood count deviations from reference values ( lewis et al . 2001 ) and biochemical blood test [ glucose , bilirubin , aspartate transaminase , alanine transaminase ( alt ) , gamma - glutamyl transferase , alkaline phosphatase , lactate dehydrogenase ( ldh ) , sodium , potassium , urea and creatinine ] deviations from reference values ( schumann et al . inclusion and exclusion criteria - this study included patients diagnosed with leprosy who were treated with the mdt regimen at the national reference centre for leprosy and sanitary dermatology from the period of january 2002-december 2009 and who had at least one year of follow - up after a medication discharge as described in their medical records . all patients with incomplete medical records , alternative medications and/or changes in dose - related mdt adverse effects ( anaemia and thrombocytopenia ) , as well as those with leprosy reactions at diagnosis and discharge were excluded from the study . clinical and operational classification criteria - the leprosy patients were diagnosed by a committee of leprosy experts based on clinical and laboratory tests and were stratified according to ridley - jopling s clinical classification ( ridley & jopling 1966 ) . for treatment purposes , all patients received an operational classification of paucibacillary ( pb ) or multibacillary ( mb ) leprosy , based on the world health organization criteria and ancillary laboratory tests . patients with less than five lesions , negative results for smears at any site , negative results for elisa anti - pgl-1 and pcr in skin smears and biopsies were classified as pb ; patients with more than five lesions , positive results for smears at any site or positive results for elisa anti - pgl-1 and pcr in skin smears and biopsies were classified as mb . criteria for definition of leprosy reactions - the leprosy reactions ( type 1 and 2 ) were identified and classified in the medical records after a confirmed diagnosis by the expert leprosy physician who attended to the patient during the clinical episode . to determine the number of reactions , the exacerbation of symptoms seven days or more after completion of the reaction treatment ( prednisone or thalidomide ) was considered to be a new reaction and symptoms that emerged in less than seven days after completion of treatment were considered to be a continuation of the previous reaction . statistical analysis - logistic regression analysis was applied to determine the degree of dependence between the independent and dependent epidemiological variables . the probability of a leprosy reaction occurring during or after treatment given the presence of a specific factor was measured by calculating the odds ratio ( or ) , along with the associated confidence intervals ( ci ) and p values . ethics - the study was approved by the ethical committee on human research of the federal university of uberlndia under registration 449/10 and protocol 193/10 . the ethical principles stated in resolution 466/2012 of the brazilian national council of health underlie the study methodology . among the 665 medical records scanned , 33.8% ( 225/625 ) were excluded for the following reasons : 10.2% ( 68/665 ) of the patients transferred to other health care facilities , 9.3% ( 62/665 ) of the patients presented with leprosy reactions at diagnosis or before the collection of samples , 5.2% ( 35/665 ) of the patients presented with leprosy reactions at discharge or at the time of the collection of samples after treatment , 5.5% ( 37/665 ) of the patients were taking alternative medications and/or had changes in doses related to mdt adverse effects ( anaemia and thrombocytopenia ) and 3.4% ( 23/665 ) had incomplete medical records . of the 66.2% ( 440/665 ) of the patients who had complete medical records and did not present leprosy reactions at diagnosis and/or discharge , 57% ( 251/440 ) presented reactions during and/or after mdt treatment and 43% ( 189/440 ) did not present reactions at any time . table i displays the frequency of the epidemiologic characteristics stratified into the two groups of patients with and without leprosy reactions and the results of the logistic regression analysis . table ilogistic regression analysis of the frequency of epidemiologic characteristics and occurrence of leprosy reactions and no reactions , uberlndia , state of minas gerais , brazil , 2002 - 2009variablesreactionsno reactionstotaln ( % ) n ( % ) n95% cipclinical presentation i0 ( 0)4 ( 2.1)4 - - tt13 ( 5.2)49 ( 25.9)620.01 - 0.10 < 0.001 bt85 ( 33.9)98 ( 51.9)1830.06 - 0.29 < 0.001 bb48 ( 19.1)12 ( 6.3)600.26 - 1.640.036 bl39 ( 15.5)16 ( 8.5)550.16 - 0.970.043 lls5 ( 2)0 ( 0)5 - - ll61 ( 24.3)10 ( 5.3)712.86 - 11.61 < 0.001operational classification pb49 ( 19.5)126 ( 66.7)1753.59 - 9.82 < 0.001 mb202 ( 80.5)63 ( 33.3)265 - -gender male172 ( 68.5)92 ( 48.7)2641.22 - 3.320.006 female79 ( 31.5)97 ( 51.3)176 - -age group 0 - 194 ( 1.6)13 ( 6.9)170.69 - 1.360.869 20 - 3957 ( 22.7)43 ( 22.8)100 - - 40 - 59131 ( 52.2)87 ( 46)218 - - = 6059 ( 23.5)46 ( 24.3)105 - -total251 ( 57)189 ( 43)440 - -bb : borderline - borderline ; bl : borderline - lepromatous ; bt : borderline - tuberculoid ; ci : confidence interval ; i : indeterminate ; ll : lepromatous - lepromatous ; lls : subpolar - lepromatous ; mb : multibacillary ; pb : paucibacillary ; tt : tuberculoid . bb : borderline - borderline ; bl : borderline - lepromatous ; bt : borderline - tuberculoid ; ci : confidence interval ; i : indeterminate ; ll : lepromatous - lepromatous ; lls : subpolar - lepromatous ; mb : multibacillary ; pb : paucibacillary ; tt : tuberculoid . leprosy reactions occurred primarily in patients classified as mb ( 80.5% , 202/251 ) , mb patients had an increased probability of having a leprosy reaction compared with all non - mb patients ( ci = 3.59 - 9.82 , p < 0.001 ) . regarding the clinical classification of the patients with a leprosy reaction , there was a predominance of borderline - tuberculoid ( bt ) patients ( 33.9% , 85/251 ) followed by lepromatous ( ll ) patients ( 24.3% , 61/251 ) . although the or of a leprosy reaction were significantly higher for males than for females ( ci = 1.22 - 3.32 , p = 0.006 ) , it should be noted that among male patients presenting reactions , 68.8% ( 139/202 ) had mb leprosy , while among females , only 31.2% had mb leprosy ( 63/202 ) . when considering ethnicity , the caucasian phenotype prevailed in the reactive group ( 53.4% , 134/251 ) , with a statistically significant increase in the or of a reaction compared with all other ethnic groups . the stratified descriptive analysis of the patients with leprosy reactions is presented in table ii . a total of 47.9% ( 211/440 ) of the patients presented reactions during treatment ; 64.5% ( 136/211 ) of the reactions were type 1 and 35.1% ( 74/211 ) were classified as bt . in the reaction group , 73.5% ( 155/211 ) developed reactions during the first three months of mdt treatment and 92.8% ( 196/211 ) developed reactions up to nine months after the initiation of treatment . in the period after the end of mdt treatment , 32.9% ( 52/158 ) presented reactions up to three months following discharge , 63.2% ( 100/158 ) up to six months and the vast majority [ 91.1% ( 144/158 ) ] presented reactions within 15 months of medication discharge . table iifrequency of patients that developed leprosy reactions during and after multidrug therapy treatment according to the clinical presentation and reaction type , uberlndia , state of minas gerais , brazil , 2002 - 2009variablesreaction typetype 1 n ( % ) mixed n ( % ) type 2 n ( % ) total n ( % ) during treatmentclinical presentation i---0 ( 0 ) tt9 ( 4.3)--9 ( 4.3 ) bt74 ( 35.1)--74 ( 35.1 ) bb38 ( 18)--38 ( 18 ) bl15 ( 7.1)5 ( 2.4)10 ( 4.7)30 ( 14.2 ) lls-5 ( 2.4)-5 ( 2.4 ) ll--55 ( 26.1)55 ( 26.1 ) total136 ( 64.5)10 ( 4.7)65 ( 30.8)211 ( 100)after treatmentclinical presentation i---0 ( 0 ) tt5 ( 3.2)--5 ( 3.2 ) bt55 ( 34.8)--55 ( 34.8 ) bb31 ( 19.6)--31 ( 19.6 ) bl10 ( 6.3)6 ( 3.8)10 ( 6.3)26 ( 16.5 ) lls-1 ( 0.6)2 ( 1.3)3 ( 1.9 ) ll--38 ( 24.1)38 ( 24.1 ) total101 ( 63.9)7 ( 4.4)50 ( 31.6)158 ( 100)bb : borderline - borderline ; bl : borderline - lepromatous ; bt : borderline - tuberculoid ; i : indeterminate ; ll : lepromatous - lepromatous ; lls : subpolar - lepromatous ; tt : tuberculoid . bb : borderline - borderline ; bl : borderline - lepromatous ; bt : borderline - tuberculoid ; i : indeterminate ; ll : lepromatous - lepromatous ; lls : subpolar - lepromatous ; tt : tuberculoid . a direct correlation was observed between the number of reactions during treatment and the anti - pgl-1 elisa serology index at diagnosis ( r = 0.2482 , p = 0.0007 ) . furthermore , an indirect correlation between the number of reactions during the treatment and the mitsuda test at diagnosis was observed ( r = -0.1545 , p = 0.0475 ) . an increased probability for the emergence of reactions during treatment was observed in patients with a positive bi ( or = 6.39 ; 95% ci : 4.1 - 10.1 ) or pcr ( or = 9.15 ; 95% ci : 5.4 - 15.5 ) in skin smears , as well as anti - pgl-1 seropositivity ( elisa ) ( or = 4.77 ; 95% ci : 2.9 - 7.9 ) ( table iii ) . regarding positive laboratory tests at the time of medical discharge , significant or were also observed for patients with a positive bi ( or = 8.47 ; 95% ci : 4.7 - 15.3 ) or pcr ( or = 6.46 ; 95% ci : 3.4 - 12.3 ) in skin smears , as well as anti - pgl-1 seropositivity ( elisa ) ( or = 2.25 ; 95% ci : 1.3 - 3.9 ) ( table iv ) . table iiidistribution of results to laboratory tests at diagnosis , odds ratio ( or ) and frequency of leprosy reactions and no reactions during treatment , uberlndia , state of minas gerais , brazil , 2002 - 2009reactions during treatmentno reactionsvariables n ( % ) n ( % ) or95% cipbi at diagnosis positive131 ( 64.2)39 ( 21.9)6.394.05 - 10.09 < 0.001 negative73 ( 35.8)139 ( 78.1)--- total204 ( 100)178 ( 100)---pcr in skin smears at diagnosis positive119 ( 77.3)39 ( 27.1)9.155.40 - 15.49 < 0.001 negative35 ( 22.7)105 ( 72.9)--- total154 ( 100)144 ( 100)---anti - pgl-1 elisa at diagnosis positive135 ( 73.8)43 ( 37.1)4.772.89 - 7.87 < 0.001 negative48 ( 26.2)73 ( 62.9)--- total183 ( 100)116 ( 100)---anti - pgl-1 : anti - phenolic glycolipid-1 ; bi : bacterial index ; ci : confidence interval ; pcr : polymerase chain reaction . anti - pgl-1 : anti - phenolic glycolipid-1 ; bi : bacterial index ; ci : confidence interval ; pcr : polymerase chain reaction . table ivdistribution of results to laboratory tests at mdt discharge , odds ratio ( or ) and frequency of leprosy reactions and no reactions after treatment , uberlndia , state of minas gerais , brazil , 2002 - 2009variablesreactions after treatmentno reactionsor95% cipn ( % ) n ( % ) bi at discharge positive73 ( 60.3)21 ( 15.2)8.474.69 - 15.28 < 0.001 negative48 ( 39.7)117 ( 84.8)--- total121 ( 100)138 ( 100)---pcr in skin smears at discharge positive64 ( 59.3)18 ( 18.4)6.463.41 - 12.25 < 0.001 negative44 ( 40.7)80 ( 81.6)--- total108 ( 100)98 ( 100)---anti - pgl-1 elisa at discharge positive71 ( 53.4)33 ( 33.7)2.251.31 - 3.870.004 negative62 ( 46.6)65 ( 66.3)--- total133 ( 100)98 ( 100)---anti - pgl-1 : anti - phenolic glycolipid-1 ; bi : bacterial index ; ci : confidence interval ; pcr : polymerase chain reaction . anti - pgl-1 : anti - phenolic glycolipid-1 ; bi : bacterial index ; ci : confidence interval ; pcr : polymerase chain reaction . through the analysis of abnormal blood cell counts and blood biochemistry tests at diagnosis , it was observed that alterations , such as leucocytosis ( or = 9.97 ; 95% ci : 3.9 - 25.7 ) , thrombocytopenia ( or = 5.72 ; 95% ci : 2.3 - 14.0 ) and elevated serum ldh ( or = 2.38 ; 95% ci : 1.4 - 4.0 ) , represented significant risks for reactions during treatment ( table v ) . the main blood count and blood biochemistry alterations that were identified at medication discharge and were potential risk factors for the occurrence of leprosy reactions after mdt treatment were anaemia ( or = 2.36 ; 95% ci : 1.2 - 4.5 ) , leucocytosis ( or = 4.14 ; 95% ci : 1.5 - 11.6 ) and thrombocytopenia ( or = 3.70 ; 95% ci : 1.3 - 2.2 ) , as listed in table vi . table vdistribution of results to haematological and biochemical tests at diagnosis , odds ratio ( or ) and frequency of leprosy reactions and no reactions during treatment , uberlndia , state of minas gerais , brazil , 2002 - 2009variablesreactions during treatmentno reactionsor95% cipn ( % ) n ( % ) anemia29 ( 13.7)16 ( 8.5)1.800.94 - 3.440.100 low haematocrit19 ( 9)7 ( 3.7)2.691.10 - 6.580.040 low haemoglobin10 ( 4.7)9 ( 4.8)1.100.43 - 2.780.979polycythaemia14 ( 6.6)6 ( 3.2)2.310.87 - 6.180.134unchanged168 ( 79.6)167 ( 88.4)---total211 ( 100)189 ( 100)---leukopenia0 ( 0)0 ( 0)---leukocytosis45 ( 21.3)5 ( 2.6)9.973.86 - 25.72 < 0.001 eosinophilia20 ( 9.5)1 ( 0.5)22.162.94 - 167.0 < 0.001 lymphocytosis15 ( 7.1)2 ( 1.1)8.311.87 - 36.890.002 neutrophilia0 ( 0)2 ( 1.1)--- targeted high10 ( 4.7)0 ( 0)---unchanged166 ( 78.7)184 ( 97.4)---total211 ( 100)189 ( 100)---thrombocytopenia33 ( 15.6)6 ( 3.2)5.722.33 - 13.98 < 0.001plaquetose3 ( 1.4)1 ( 0.5)3.120.32 - 30.280.595unchanged175 ( 82.9)182 ( 96.3)---total211 ( 100)189 ( 100)---hypoglycaemia8 ( 3.8)1 ( 0.5)7.671.76 - 2.120.056hyperglycaemia30 ( 14.2)22 ( 11.6)1.300.72 - 2.360.455unchanged173 ( 82)166 ( 87.8)---total211 ( 100)189 ( 100)---elevated serum lactate dehydrogenase60 ( 28.4)27 ( 14.3)2.381.43 - 3.950.001unchanged151 ( 71.6)162 ( 85.7)---total211 ( 100)189 ( 100)---ci : confidence interval . table vidistribution of results to haematological and biochemical tests at multidrug therapy discharge , odds ratio ( or ) and frequency of leprosy reactions and no reactions after treatment , uberlndia , state of minas gerais , brazil , 2002 - 2009variablesreactions after treatmentno reactionsor95% cipn ( % ) n ( % ) anemia29 ( 18.4)16 ( 8.5)2.361.23 - 4.540.013 low haematocrit12 ( 7.6)7 ( 3.7)2.230.85 - 5.840.149 low haemoglobin17 ( 10.8)9 ( 4.8)2.461.06 - 5.700.050polycythaemia1 ( 0.6)6 ( 3.2)0.210.02 - 1.820.249unchanged128 ( 81)167 ( 88.4)---total158 ( 100)189 ( 100)---leukopenia0 ( 0)0 ( 0)---leukocytosis16 ( 10.1)5 ( 2.6)4.141.48 - 11.580.007 eosinophilia5 ( 3.1)1 ( 0.5)6.470.74 - 56.070.126 lymphocytosis7 ( 4.4)2 ( 1)4.530.92 - 22.160.089 monocytosis2 ( 1.3)0 ( 0)--- neutrophilia0 ( 0)2 ( 1)--- targeted high2 ( 1.3)0 ( 0)---unchanged142 ( 89.9)184 ( 97.4)---total158 ( 100)189 ( 100)---thrombocytopenia17 ( 10.8)6 ( 3.2)3.701.29 - 2.230.008plaquetose2 ( 1.3)1 ( 0.5)2.610.23 - 29.170.820unchanged139 ( 88)182 ( 96.3)---total158 ( 100)189 ( 100)---hypoglycaemia6 ( 3.8)1 ( 0.5)7.541.99 - 2.530.073hyperglycaemia20 ( 12.7)22 ( 11.6)1.140.59 - 2.180.810unchanged132 ( 20.3)27 ( 14.3)1.520.86 - 2.670.183unchanged126 ( 79.7)162 ( 85.7)---total158 ( 100)189 ( 100)---ci : confidence interval ci : confidence interval because leprosy reactions are recognised as being closely related to the morbidity and disability associated with disease progression ( foss et al . 2005 ) , several studies have investigated the risk factors for these acute episodes . co - infections , anti - pgl-1 seropositivity and positive pcr results in skin biopsies have been suggested as predictive variables ( sousa et al . this study presents new potential markers , providing an improvement in the early identification of leprosy reactions during and after mdt treatment . at the time of diagnosis , leucocytosis , thrombocytopenia and elevated serum ldh leucocytosis and thrombocytopenia , regardless of the leprosy clinical presentation , could indicate an underlying inflammatory process or infection that could trigger the reaction ; this finding supports other studies that point to underlying infections as a risk factor for the development of reactions ( pfaltzgraff & ramu 1994 ) . ldh , the levels of which increase due to cellular damage , is an enzyme that is present in almost all body tissues . tissue injury related to nerve damage , regardless of the clinical form , could explain the elevated levels observed , indicating this as a risk factor for both types of leprosy reactions . the results at medical discharge suggested that abnormalities such as anaemia , leucocytosis and thrombocytopenia may also be risk factors for both types of leprosy reactions after mdt treatment ; the blood abnormalities were found in similar proportions in patients from across the clinical spectrum . the nearly 60% frequency of patients presenting leprosy reactions during and/or after treatment observed in this study was slightly higher than that found in another study ( 43.5% ; 290 patients ) with a similar sample size ( 667 ) ( silva & griep 2007 ) . according to the operational classification distribution , mb patients accounted for more than 80% of the cases that developed leprosy reactions , a fact that is associated with the patients bacterial load and the prevalence of borderline individuals ( patients immunologically unstable ) in endemic areas . in a previous study carried out in india with 2,600 patients who presented leprosy reactions , mb patients represented more than half of the sample , in accordance with our results ( kumar et al . an analysis of the clinical spectrum , regardless of the period , revealed that patients who presented the most reactions had ll leprosy , followed by borderline - borderline and borderline - lepromatous leprosy . a previous study reported that ll patients were the most likely patient group to develop reactions during and after discharge , during an evaluation period of five years ( jacob et al . less than 50% of the patients with bt leprosy developed reactions and bt / mb patients presented twice the number of reactions than bt / pb patients . the condensed bacterial load , shown in this study through the bi and pcr for m. leprae detection , could justify the higher frequency of reactions among mb patients . as demonstrated , the bi conferred a greater probability of developing leprosy reactions regardless of the disease period ; however , the risk decreased after treatment . the or calculated for the occurrence of leprosy reactions during and after mdt treatment was significant when the bi was positive at both diagnosis and discharge . a previous study from our group demonstrated that there was a positive correlation between bi = 2 and a greater number of reactions ( rodrigues et al . 2001 ) . another study on the association between leprosy reactions and the bacterial load , assessed through the initial positive bi , revealed an or of 2.94 ; however , the or was not statistically significant and the study lacked a control group ( brito et al . the or observed for positive pcr results in skin smears at diagnosis and discharge related to the development of leprosy reactions during and after mdt treatment , respectively , presented both relevance and agreement with previous studies demonstrating positive pcr results in skin biopsies as a risk factor for type 1 reactions ( sousa et al . a positive correlation was observed between the values of the anti - pgl-1 elisa serology at diagnosis and the number of leprosy reactions during treatment , reiterating that the increase in specific antibodies against mycobacterium leprae is a consequence of humoral immune response activation and increased bacterial load , thus stimulating the development of reactions ( bher - skula et al . leprosy reactions are frequently associated with successful treatment , wherein the degradation of killed bacilli causes the release of antigens and stimulates antibody production and cell - mediated immune responses ( spencer et al . there was a negative correlation between the values of the mitsuda test at diagnosis , which measures the cell - mediated immune response specific to m. leprae and the number of reactions during treatment . when the values of the mitsuda test increase , the bacterial load decreases , favouring a lower incidence of leprosy reactions ( kar & job 2005 ) . the measurement of the bacillary load through elisa anti - pgl-1 positivity and its relation to mb leprosy ( bher - skula et al . 2003 ) not only helps to identify mb patients , it also indicates the presence of subclinical infection and can be used as a measure of treatment efficacy ( oskam et al . a higher frequency of reactions during treatment than after treatment was observed , which could be influenced by the bacterial clearance and improvement of cell - mediated immunity established by the treatment . these findings were consistent with the results of previous studies that compared patients who developed reactions during treatment and after discharge ( brito et al . more than 70% of the patients developed their first reaction within the first three months after the initiation of treatment , which could be related to the intense release of m. leprae antigens due to the antibacterial action of mdt ( naafs 1994 ) . after treatment , more than 90% of the patients presented their first reaction within the first 15 months , supporting results from a previous study by our research group that reported that the majority of reactions occurred in the first 12 months ( rodrigues et al . 2001 ) . the results of the present study showed a predominance of males among the reactive patients and were in agreement with the results of a study of 201 leprosy patients in the city of recife , state of pernambuco , brazil ( teixeira et al . it is noteworthy that more than half of the male patients who presented with reactions had mb leprosy , while only one - third of the female patients with reactions were classified as mb leprosy ; this result demonstrates a clear association of male gender with mb leprosy , which may explain the higher number of males among the patients who presented with leprosy reactions . the patients who presented reactions in this study were predominantly in the age range of 40 - 59 years , with no significant relationship between this variable and the occurrence of leprosy reactions . nevertheless , a previous study demonstrated a statistically significant relative risk related to the appearance of leprosy reactions when the patient age was greater than or equal to 40 years ( sousa et al . this study demonstrated that as age increases , the percentage of mb individuals also increases , which reinforces the idea that as the risk of infection decreases in a community , the age at which people become infected and the proportion of mb leprosy increase , potentially due to a longer incubation period ( gil surez & lombardi 1997 ) . finally , the results showed that low - cost laboratory tests , performed routinely in most health care facilities , can be used along with other likely prognostic markers , such as anti - pgl-1 serology , for the identification and monitoring of individuals at greater risk of developing leprosy reactions , either during or after mdt treatment . further evidence will support the implementation of new strategies of prevention , control and management of leprosy reactions , allowing for the timely development of a treatment plan to prevent nerve damage and , therefore , the appearance of the disabling sequelae associated with the stigma of this disease .
this cross - sectional retrospective study evaluated 440 leprosy patients ; 57% ( 251/440 ) had leprosy reactions during and/or after multidrug therapy , 80.5% ( 202/251 ) of whom presented with multibacillary leprosy . at diagnosis , positive bacterial index ( bi ) [ odds ratio ( or ) = 6.39 ; 95% confidence interval ( ci ) : 4.1 - 10.1 ) ] or polymerase chain reaction ( pcr ) ( or = 9.15 ; 95% ci : 5.4 - 15.5 ) in skin smears , anti - phenolic glycolipid-1 ( anti - pgl-1 ) elisa ( or = 4.77 ; 95% ci : 2.9 - 7.9 ) , leucocytosis ( or = 9.97 ; 95% ci : 3.9 - 25.7 ) , thrombocytopenia ( or = 5.72 ; 95% ci : 2.3 - 14.0 ) and elevated lactate dehydrogenase ( or = 2.38 ; 95% ci : 1.4 - 4.0 ) were potential markers for the development of reactions during treatment . after treatment , positive bi ( or = 8.47 ; 95% ci : 4.7 - 15.3 ) and pcr ( or = 6.46 ; 95% ci : 3.4 - 12.3 ) in skin smears , anti - pgl-1 elisa ( or = 2.25 ; 95% ci : 1.3 - 3.9 ) , anaemia ( or = 2.36 ; 95% ci : 1.2 - 4.5 ) , leucocytosis ( or = 4.14 ; 95% ci : 1.5 - 11.6 ) and thrombocytopenia ( or = 3.70 ; 95% ci : 1.3 - 2.2 ) were risk factors for the occurrence of reactions during the study period . the identification of groups with an increased risk for developing reactions will allow for the timely development of a treatment plan to prevent nerve damage and , therefore , the appearance of the disabling sequelae associated with the stigma of leprosy .
the attempt to clarify this concept of which longed for more than 50 years begun with this question : who is a medical expert ? to answer this question , we introduce three leading theories introduced in the area of clinical reasoning , known as : knowledge structure , hypothetic- deductive , and dual process ( 1 - 4 ) . being or becoming an expert are defined differently in each theory . during the course of time , methods of assessment for identification of experts were changed , and in each period various clinical reasoning tests were suggested to distinguish experts from novices , all inspired by the expert concept dominated in that time . providing new clinical reasoning tests while the main purpose of clinical reasoning tests is discriminating expert from novice , the definition of expert provided by the existing theories must be also taken into account . giving a precise definition of medical expert , we tried to categorize and introduce the most applied clinical reasoning tests within the framework of the main existing theories . this categorization was performed according to the similarity and distinction criteria for expert and novice within the existing theories . this categorization could help researchers recognize tests with more conformity with the concept of expertise . it is also supposed that this study will provide educators with the opportunity to expand contemporary clinical reasoning assessment tools , apply tests in their proper situation , and to raise considerations for future research in the field . early attempts on assessing clinical reasoning skill was based on the idea that considered " clinical reasoning ability " as an individual trait or special personal characteristics ( 3,5 ) . it was also believed that experts have a different mental strategies or heuristics to solve problem which is " domain ( content)-independent " ( 4,6 ) . thus , an expert was distinguished for his / her special mental ability he / she had for reasoning . therefore , many attempts were made to create some procedural instruments by which it was possible to know to what extent performance of physicians ( as examinee ) and experts ( as reference group ) are matched during the reasoning process . in this regard , multi - stage assessment tests were created . it means that test providers emphasized on the intermediate phases of problem solving while encountering a simulated clinical situation and not merely final diagnosis or management plan ( 3,5,7 ) . as such , rimoldi in1961 advised his method of knowing how a medical student proceeds when posing a clinical situation ( 8) . the tool itself consisted of some two - sided cards . one side of each card contained some questions that a participant may ask of a patient . on the other side , he / she receives related information like x - ray findings , laboratory results , etc . an examiner was responsible for writing the number of selected cards in the same order in which they are selected . scoring was based on the number of questions asked , their usefulness for the final diagnoses , and the order in which they are asked . it provided some opportunities to study the process decided by a subject when diagnosing a case . rimoldi created a tool by which it could possibly clear some parts of diagnosis remained uncovered through ordinary true - false or multiple choices tests . he succeeded to make a new approach ( maybe qualitative one ) to analyze the pattern used by both experts / novices to reach diagnoses ( 8) . the results showed that junior students used fewer questions than seniors and the number of irrelevant and redundant questions asked by juniors was considerably high compared with senior groups ( 8) . there was also a kind of less known test known as programmed test , used by the national board of medical examiners in the u.s . , consisted of three parts : primary clinical information about a patient , some probable diagnoses , and investigations a participant may select to confirm the diagnosis . participants were scored for the number of correct decisions they made ( 5,9,10 ) . in the early 1970 , the model explored the cognitive process of problem solving in experts in two phases : hypothesis generation and hypothesis testing ( 2,11 - 13 ) . hypothetic - deductive model seemed to be the best answer to the question of how experts think . on that idea , some tools like branched management problems , diagnostic management problems and sequential management problems were developed from1965 to 1975 . patient problem management ( pmp ) was the improved version of these kinds of tests ( 9 , 14 ) . pmp was known as the best paper - based simulation method . during some few years , this method became very popular and many improved versions were suggested ( 15 ) . it was claimed that pmp can offer a practical means of assessing both process and product of clinical reasoning ( 16 ) . there were booklets containing short case reports and some data on history , diagnoses and therapeutic works . participants were asked to sequentially match them with the given cases . some changes to the method like invisible ink , tabs and latent print image made it much more energetic and truthful ( 17 - 19 ) . participants were scored based on the data of correct selections and taken pathways . except for many problems existed in using the test ( to be expensive in time and running , to be difficult having experts consensus on the correct answer and way ) , there was also low correlations between the physicians performance and the problems . this occurred frequently in pmp tests with all kinds of problems and scoring methods ( 11,14,20,21 ) . the phenomenon was named " content specificity " which contradicted with the beliefs that introduced reasoning as the skill independent from " knowledge structure " ( 11 ) . extended matching questions ( emqs ) proposed in 1980s are multiple choice questions ; each consisted of a problematic clinical case with just one correct answer within a list of at least 7 options . they were assumed as a reasonable alternative to either multiple choice questions or free response tests ( 23 ) . it has been used by national board of medical examiners ( nbme ) and u.s medical licensing examination board ( uslme ) ( 23 ) . scoring of emq is based on the number of right diagnoses and the type of reasoning that participants verbally describe through the process . there were some critics who believed the emq is highly dependent on student 's memory with a little attention to the process of hypothesis testing . however , number of studies that emphasized on its ability to assess problem solving skill is considerable . one of the most important limitations in using emq is the increased work for faculty members when adapting to the emqs tests . there was also low correlation between physicians ' performance and sequential problems in an equal domain . in addition , they often are designed for assessing diagnostic reasoning not all types of clinical situations like treatment and following ( 23 - 29 ) . triple - jump ( tj ) test was an assessment method originated from mcmaster curriculum aimed to estimate student 's clinical reasoning skill . the first step follows by a 2 hour session for self- directed learning based on new issues a student learned from step one . then , there is a 30 minute session for giving report and feed - back . the first version of the examination was in oral format and graded ( pass or fail ) subjectively ( 30,14 ) by faculties . the next versions were improved by adding a written part to the oral test which allowed the faculties to grade it objectively ( 31,32,11 ) . tj examination was an actual method to assess student 's competency in the setting of problem based curriculum . it was a kind of assessment method which its proper effects on learning were proved ( 14 ) . however , the tool had many problems of validity and reliability for standardization ( 30 ) . clinical reasoning exercise ( cre ) was proposed to problem based learning ( pbl ) medical schools as a multiple question test which had more reliability compared to tj . they were some oral or written tests which could evaluate different aspect of student competency through engaging them in problem solving process . however , it 's inter - rater and inter- case correlations , concurrent validity and reliability is yet open to challenge . some authors also believed that cres could assess student s knowledge not their clinical reasoning skill ( 9,31 - 34 ) . clinical reasoning problems ( crps ) introduced as the best tool that can purely assess the process of reasoning ( 35 ) . , examinees are asked to nominate two from the most probable diagnoses among a list of diagnoses suggested for a short scenario . then , examinees should mark some given findings in the next stage and determine which of them support or reject his / her selected diagnoses respectively . however there are also some controversial findings on the construct validity of crp method and its ability to determine the process that leads to the outcomes ( 9,36 ) . hypothetico - deductive paradigm s major emphasis in providing the tests was on a set of reasoning strategies or heuristics through which experts could solve clinical problems successfully . thus , related assessment tests were multi stage- largely domain - independent- and were assumed as having the capability of differentiates experts from novices . elstein et al showed that problem solving heuristics is strongly dependent on acquired knowledge ( 6 ) . therefore , content- specificity phenomenon casted a big doubt on definition of experts and the ways they are identified according to hypothetico - deductive paradigm . given evidence presented above , it was believed that experts should use hypothetico - deductive model to possibly solve any problem encountered . however , it was found that clinical reasoning skill is specific to the problem encountered as was shown by the low inter - case correlations in clinicians ' performance ( content specificity ) ( 4 ) . early cognitive psychological research also emphasized on related knowledge as an essential determinant of successful problem solving . besides however , some pmps results demonstrated that intermediate students scores of pmps were upper than those of experienced experts . this fact surprised those who believed experts may have considerably more explicit knowledge than novices ( 14 ) . again , cognitive psychology presented an explanation : experts did not necessarily have more " knowledge " but compared to students , they have the ability to organize their specific knowledge more efficiently ( 2 ) . this changed researchers approach toward " knowledge structure " , " expert process " and " knowledge itself " . scripts are like schema , but have some orderly actions or events which are essential to achieve a goal . script theory was first introduced to the field of medical education to explain the differences between experts and novices in their practice ( 37 ) . also known as semantic networks , illness scripts or instance scripts ( 38,39 ) , these kinds of networks help experts to remember relevant knowledge easier than students , thus , they solve a clinical problem more successfully . in other words , problem solving appeared to involve the way a person organizes his / her knowledge and experience in the brain ( 40 - 42 ) . thus , attempts started to create an instrument to estimate variation and quality of illness scripts in physicians ' mind . according to the script theory , while diagnosis clinicians take cues from relevant hypothesis in their minds . this psychological view helped investigators to use a new approach in assessing clinical reasoning naming scrip concordance tests ( scts ) ( 43 ) . scts were designed to evaluate the richness of mental networks and the capacity of data interpretation in decision making situations . the test approach consisted of short scenarios followed by some questions categorized in three sections . section three was a five - point likert scale by which examiners were able to evaluate participants ' decisions . the clinical reasoning competency of each examinee was evaluated according to the percent of concordance between examinee decisions and expert panel decisions . sct let examinees make decisions for to a problematic situation through analysis of available data ( 43 - 50 ) . some studies have showed that the reliability and validity of sct are good and its reliability directly related to the experience of physicians . however , some research findings on its differential and predictive powers are not considerable ( 51 - 53 ) . key features ( kf ) test was suggested in 1987 and implemented in 1992 as one section in mcc qualifying examination ( mccqe ) ( 54 ) . it was a good replacement for pmp test because of the increased reliability due to wider sampling of cases and more attention on evaluating the important steps ( key features ) in determination of a problem ( 55 ) . it seems that the ability of a person to gather critical data during a clinical decision depends on the related script exists in her / his mind . thus , kf test could be also considered as a tool for evaluating the adequacy ( richness ) of scripts ( 56 - 59 ) . another tool to evaluate diagnostic thinking and clinical reasoning is comprehensive integrative puzzle ( cip ) ( 60 ) . cip is an ' extended matching ' crossword puzzle of various disciplinary elements of more than 4 clinical situations . its answer sheet is a matrix with rows and columns and examinees are asked to fill its cells through matching all related parts of findings and create a complete picture of a clinical problem . each completed column shows the student 's proficiency in analyzing medical history , physical examination , laboratory test results and , sometimes , some related interventions . it is shown that cip is extensively accepted by students because there is too much fun in matching puzzle components ( 1,61 ) . one of the main limitations of utilizing cip is its low reliability due to lack of a complete agreement among experts panel . thus , test providers should have scant attention to transparency and enough details of tests . a combination of comprehensive integrative puzzles and extended matching questions ( emq ) has been proposed to assess most aspects of clinical reasoning , particularly for the computer based assessment approaches ( 60 ) . scenario formation test ( sf ) is one of the newest assessment methods in the field of clinical reasoning ( 61 ) . sf reports an examinee is required to write two separate scenarios according to some given signs and symptoms and determine a diagnosis for each of them . scenarios are viewed by two expert members and scored according to a standard checklist . correct diagnosis and appropriateness of using signs and symptoms to complete scenario are considered as main criteria in scoring test ( 1,61 ) . therefore , compared to tests with process approach , it seemed that tests with knowledge structure had a better approach toward defining the expert , resulted in a shift from multi - stage , single - question to single - stage multi - question . to prove this claim we have to compare the pmp test with other tests such as scenario and puzzle . the knowledge structure paradigm claims that the contents and richness of every script correspond to a physician s expertise in a way that he / she might qualify for the rich scripts in his / her expertise , while , on the other hand , he / she lacks any scripts or owns weak scripts in clinical situations not appropriate for his / her expertise . in this regard , the results of some studies have shown that experts when are faced with clinical tests unrelated to their expertise acquire lower scores . moreover , these studies have also revealed that the evaluation scores of experts in areas unrelated to their expertise are higher than those of novices . the question is that , based on what kind of reasoning the experts can manage clinical situations unrelated to their expertise ? and why non - knowledge structure approach is unable to distinguish them from novices ? other studies showed that , in managing clinical situations unrelated to their field of expertise , experts use reasoning process approach instead of knowledge structure approach . in other words , the expert performs better than the novice in both areas of process approach and knowledge structure approach . therefore , despite the fact that the tests of knowledge structure approach significantly corresponded to the characteristics of experts , they were not able to evaluate the expert in situations other than his / her field of expertise . thus , the mere use of knowledge structure approach tests does not seem to properly evaluate individual 's expertise . therefore , an expert is a person more successful than a novice in using both reasoning approaches ; this definition for expert has not been offered in the mentioned two clinical reasoning approaches . some scholars claim that the hypothetico - deductive approach and knowledge structure approach denote analytical reasoning and non - analytical reasoning , respectively . they believe that general model of reasoning could apply to analyze an unfamiliar situation in which there is no related script . in contrast , knowledge structure reasoning is applied in handling every familiar problem in which there is no need to analyze situation ( 63,64 ) . therefore , the significance of expertise evaluation was determined based on individual 's skills in both analytical and non - analytical areas as it will be discussed in the next part . further studies have suggested a more comprehensive model of clinical reasoning in which analytical and non- analytical approaches are combined . the combined model shows that reasoning could proceed in both directions of analytical and non - analytical , while encountering a clinical problem ( 3 ) . the two domains should be considered interactive instead of two separate parts or lying along a continuum . effective medical diagnosis and management are affected by analytical and non - analytical thinking modes which work together to handle all types of clinical practice situations ( 63,64 ) . thus , greater awareness on the part of combined model has underlined the need to provide examinee with some new clinical reasoning tests that could better evaluate them in situations in need of bi - directional reasoning . the nature of dual process theory which defines an expert as a person with the flexibility to switch between two modes of thinking with high performance in both types , confirms the idea that expert could not be identified by a single test emerged from analytic or non - analytic thinking approach . it means that the methods of clinical reasoning evaluation in future should be able to test both skills of clinical reasoning , i.e. , analytical and non - analytical ( 64 ) . early attempts on assessing clinical reasoning skill was based on the idea that considered " clinical reasoning ability " as an individual trait or special personal characteristics ( 3,5 ) . it was also believed that experts have a different mental strategies or heuristics to solve problem which is " domain ( content)-independent " ( 4,6 ) . thus , an expert was distinguished for his / her special mental ability he / she had for reasoning . therefore , many attempts were made to create some procedural instruments by which it was possible to know to what extent performance of physicians ( as examinee ) and experts ( as reference group ) are matched during the reasoning process . in this regard , multi - stage assessment tests were created . it means that test providers emphasized on the intermediate phases of problem solving while encountering a simulated clinical situation and not merely final diagnosis or management plan ( 3,5,7 ) . as such , rimoldi in1961 advised his method of knowing how a medical student proceeds when posing a clinical situation ( 8) . the tool itself consisted of some two - sided cards . one side of each card contained some questions that a participant may ask of a patient . on the other side , he / she receives related information like x - ray findings , laboratory results , etc . an examiner was responsible for writing the number of selected cards in the same order in which they are selected . scoring was based on the number of questions asked , their usefulness for the final diagnoses , and the order in which they are asked . it provided some opportunities to study the process decided by a subject when diagnosing a case . rimoldi created a tool by which it could possibly clear some parts of diagnosis remained uncovered through ordinary true - false or multiple choices tests . he succeeded to make a new approach ( maybe qualitative one ) to analyze the pattern used by both experts / novices to reach diagnoses ( 8) . the results showed that junior students used fewer questions than seniors and the number of irrelevant and redundant questions asked by juniors was considerably high compared with senior groups ( 8) . there was also a kind of less known test known as programmed test , used by the national board of medical examiners in the u.s . , consisted of three parts : primary clinical information about a patient , some probable diagnoses , and investigations a participant may select to confirm the diagnosis . participants were scored for the number of correct decisions they made ( 5,9,10 ) . in the early 1970 , the model explored the cognitive process of problem solving in experts in two phases : hypothesis generation and hypothesis testing ( 2,11 - 13 ) . hypothetic - deductive model seemed to be the best answer to the question of how experts think . on that idea , some tools like branched management problems , diagnostic management problems and sequential management problems were developed from1965 to 1975 . patient problem management ( pmp ) was the improved version of these kinds of tests ( 9 , 14 ) . pmp was known as the best paper - based simulation method . during some few years , this method became very popular and many improved versions were suggested ( 15 ) . it was claimed that pmp can offer a practical means of assessing both process and product of clinical reasoning ( 16 ) . there were booklets containing short case reports and some data on history , diagnoses and therapeutic works . participants were asked to sequentially match them with the given cases . some changes to the method like invisible ink , tabs and latent print image made it much more energetic and truthful ( 17 - 19 ) . participants were scored based on the data of correct selections and taken pathways . except for many problems existed in using the test ( to be expensive in time and running , to be difficult having experts consensus on the correct answer and way ) this occurred frequently in pmp tests with all kinds of problems and scoring methods ( 11,14,20,21 ) . the phenomenon was named " content specificity " which contradicted with the beliefs that introduced reasoning as the skill independent from " knowledge structure " ( 11 ) . extended matching questions ( emqs ) proposed in 1980s are multiple choice questions ; each consisted of a problematic clinical case with just one correct answer within a list of at least 7 options . they were assumed as a reasonable alternative to either multiple choice questions or free response tests ( 23 ) . it has been used by national board of medical examiners ( nbme ) and u.s medical licensing examination board ( uslme ) ( 23 ) . scoring of emq is based on the number of right diagnoses and the type of reasoning that participants verbally describe through the process . there were some critics who believed the emq is highly dependent on student 's memory with a little attention to the process of hypothesis testing . however , number of studies that emphasized on its ability to assess problem solving skill is considerable . one of the most important limitations in using emq is the increased work for faculty members when adapting to the emqs tests . there was also low correlation between physicians ' performance and sequential problems in an equal domain . in addition , they often are designed for assessing diagnostic reasoning not all types of clinical situations like treatment and following ( 23 - 29 ) . triple - jump ( tj ) test was an assessment method originated from mcmaster curriculum aimed to estimate student 's clinical reasoning skill . the first step follows by a 2 hour session for self- directed learning based on new issues a student learned from step one . then , there is a 30 minute session for giving report and feed - back . the first version of the examination was in oral format and graded ( pass or fail ) subjectively ( 30,14 ) by faculties . the next versions were improved by adding a written part to the oral test which allowed the faculties to grade it objectively ( 31,32,11 ) . tj examination was an actual method to assess student 's competency in the setting of problem based curriculum . it was a kind of assessment method which its proper effects on learning were proved ( 14 ) . however , the tool had many problems of validity and reliability for standardization ( 30 ) . clinical reasoning exercise ( cre ) was proposed to problem based learning ( pbl ) medical schools as a multiple question test which had more reliability compared to tj . they were some oral or written tests which could evaluate different aspect of student competency through engaging them in problem solving process . however , it 's inter - rater and inter- case correlations , concurrent validity and reliability is yet open to challenge . some authors also believed that cres could assess student s knowledge not their clinical reasoning skill ( 9,31 - 34 ) . clinical reasoning problems ( crps ) introduced as the best tool that can purely assess the process of reasoning ( 35 ) . , examinees are asked to nominate two from the most probable diagnoses among a list of diagnoses suggested for a short scenario . then , examinees should mark some given findings in the next stage and determine which of them support or reject his / her selected diagnoses respectively . however there are also some controversial findings on the construct validity of crp method and its ability to determine the process that leads to the outcomes ( 9,36 ) . hypothetico - deductive paradigm s major emphasis in providing the tests was on a set of reasoning strategies or heuristics through which experts could solve clinical problems successfully . thus , related assessment tests were multi stage- largely domain - independent- and were assumed as having the capability of differentiates experts from novices . elstein et al showed that problem solving heuristics is strongly dependent on acquired knowledge ( 6 ) . therefore , content- specificity phenomenon casted a big doubt on definition of experts and the ways they are identified according to hypothetico - deductive paradigm . given evidence presented above , it was believed that experts should use hypothetico - deductive model to possibly solve any problem encountered . however , it was found that clinical reasoning skill is specific to the problem encountered as was shown by the low inter - case correlations in clinicians ' performance ( content specificity ) ( 4 ) . early cognitive psychological research also emphasized on related knowledge as an essential determinant of successful problem solving . besides however , some pmps results demonstrated that intermediate students scores of pmps were upper than those of experienced experts . this fact surprised those who believed experts may have considerably more explicit knowledge than novices ( 14 ) . again , cognitive psychology presented an explanation : experts did not necessarily have more " knowledge " but compared to students , they have the ability to organize their specific knowledge more efficiently ( 2 ) . this changed researchers approach toward " knowledge structure " , " expert process " and " knowledge itself " . scripts are like schema , but have some orderly actions or events which are essential to achieve a goal . script theory was first introduced to the field of medical education to explain the differences between experts and novices in their practice ( 37 ) . also known as semantic networks , illness scripts or instance scripts ( 38,39 ) , these kinds of networks help experts to remember relevant knowledge easier than students , thus , they solve a clinical problem more successfully . in other words , problem solving appeared to involve the way a person organizes his / her knowledge and experience in the brain ( 40 - 42 ) . thus , attempts started to create an instrument to estimate variation and quality of illness scripts in physicians ' mind . according to the script theory , while diagnosis clinicians take cues from relevant hypothesis in their minds . this psychological view helped investigators to use a new approach in assessing clinical reasoning naming scrip concordance tests ( scts ) ( 43 ) . scts were designed to evaluate the richness of mental networks and the capacity of data interpretation in decision making situations . it directly evaluated knowledge organization . the test approach consisted of short scenarios followed by some questions categorized in three sections . section three was a five - point likert scale by which examiners were able to evaluate participants ' decisions . the clinical reasoning competency of each examinee was evaluated according to the percent of concordance between examinee decisions and expert panel decisions . sct let examinees make decisions for to a problematic situation through analysis of available data ( 43 - 50 ) . some studies have showed that the reliability and validity of sct are good and its reliability directly related to the experience of physicians . however , some research findings on its differential and predictive powers are not considerable ( 51 - 53 ) . key features ( kf ) test was suggested in 1987 and implemented in 1992 as one section in mcc qualifying examination ( mccqe ) ( 54 ) . it was a good replacement for pmp test because of the increased reliability due to wider sampling of cases and more attention on evaluating the important steps ( key features ) in determination of a problem ( 55 ) . it seems that the ability of a person to gather critical data during a clinical decision depends on the related script exists in her / his mind . thus , kf test could be also considered as a tool for evaluating the adequacy ( richness ) of scripts ( 56 - 59 ) . another tool to evaluate diagnostic thinking and clinical reasoning is comprehensive integrative puzzle ( cip ) ( 60 ) . cip is an ' extended matching ' crossword puzzle of various disciplinary elements of more than 4 clinical situations . its answer sheet is a matrix with rows and columns and examinees are asked to fill its cells through matching all related parts of findings and create a complete picture of a clinical problem . each completed column shows the student 's proficiency in analyzing medical history , physical examination , laboratory test results and , sometimes , some related interventions . it is shown that cip is extensively accepted by students because there is too much fun in matching puzzle components ( 1,61 ) . one of the main limitations of utilizing cip is its low reliability due to lack of a complete agreement among experts panel . thus , test providers should have scant attention to transparency and enough details of tests . a combination of comprehensive integrative puzzles and extended matching questions ( emq ) has been proposed to assess most aspects of clinical reasoning , particularly for the computer based assessment approaches ( 60 ) . scenario formation test ( sf ) is one of the newest assessment methods in the field of clinical reasoning ( 61 ) . sf reports an examinee is required to write two separate scenarios according to some given signs and symptoms and determine a diagnosis for each of them . scenarios are viewed by two expert members and scored according to a standard checklist . correct diagnosis and appropriateness of using signs and symptoms to complete scenario are considered as main criteria in scoring test ( 1,61 ) . therefore , compared to tests with process approach , it seemed that tests with knowledge structure had a better approach toward defining the expert , resulted in a shift from multi - stage , single - question to single - stage multi - question . to prove this claim we have to compare the pmp test with other tests such as scenario and puzzle . the knowledge structure paradigm claims that the contents and richness of every script correspond to a physician s expertise in a way that he / she might qualify for the rich scripts in his / her expertise , while , on the other hand , he / she lacks any scripts or owns weak scripts in clinical situations not appropriate for his / her expertise . in this regard , the results of some studies have shown that experts when are faced with clinical tests unrelated to their expertise acquire lower scores . moreover , these studies have also revealed that the evaluation scores of experts in areas unrelated to their expertise are higher than those of novices . the question is that , based on what kind of reasoning the experts can manage clinical situations unrelated to their expertise ? and why non - knowledge structure approach is unable to distinguish them from novices ? other studies showed that , in managing clinical situations unrelated to their field of expertise , experts use reasoning process approach instead of knowledge structure approach . in other words , the expert performs better than the novice in both areas of process approach and knowledge structure approach . therefore , despite the fact that the tests of knowledge structure approach significantly corresponded to the characteristics of experts , they were not able to evaluate the expert in situations other than his / her field of expertise . thus , the mere use of knowledge structure approach tests does not seem to properly evaluate individual 's expertise . therefore , an expert is a person more successful than a novice in using both reasoning approaches ; this definition for expert has not been offered in the mentioned two clinical reasoning approaches . some scholars claim that the hypothetico - deductive approach and knowledge structure approach denote analytical reasoning and non - analytical reasoning , respectively . they believe that general model of reasoning could apply to analyze an unfamiliar situation in which there is no related script . in contrast , knowledge structure reasoning is applied in handling every familiar problem in which there is no need to analyze situation ( 63,64 ) . therefore , the significance of expertise evaluation was determined based on individual 's skills in both analytical and non - analytical areas as it will be discussed in the next part . further studies have suggested a more comprehensive model of clinical reasoning in which analytical and non- analytical approaches are combined . the combined model shows that reasoning could proceed in both directions of analytical and non - analytical , while encountering a clinical problem ( 3 ) . the two domains should be considered interactive instead of two separate parts or lying along a continuum . effective medical diagnosis and management are affected by analytical and non - analytical thinking modes which work together to handle all types of clinical practice situations ( 63,64 ) . thus , greater awareness on the part of combined model has underlined the need to provide examinee with some new clinical reasoning tests that could better evaluate them in situations in need of bi - directional reasoning . the nature of dual process theory which defines an expert as a person with the flexibility to switch between two modes of thinking with high performance in both types , confirms the idea that expert could not be identified by a single test emerged from analytic or non - analytic thinking approach . it means that the methods of clinical reasoning evaluation in future should be able to test both skills of clinical reasoning , i.e. , analytical and non - analytical ( 64 ) . in this paper , more than 50 years of effort made by researchers to identify clinical experts characteristics were investigated . the earliest theory of clinical reasoning emphasized on the special mental stages an expert proceeds to solve a clinical problem . it was hypothetico - deductive reasoning through which an expert creates some clinical hypothesis and evaluates them deductively . it led in creating multi - stages , single - question assessment tests like pmp , cre , tj and crp . using these kinds of assessment tools showed the extent of similarity between the steps a participant and an expert take to solve a clinical problem ( 1 - 36 ) . knowledge structure reasoning suggested illness script as a cognitive framework to explain how medical knowledge is organized and applied to a clinical situation . it revealed that more experienced physicians have much of the rich illness scripts which enable them to handle many clinical situations in their field of expertise successfully . therefore , the related tests were created in a way that could investigate the similarity of illness script of participants with those of expert panel . accordingly , medical expert is a person whose illness scripts are as rich as those of expert panel . thus , multi - stages , single - question assessment tools with focus on the cognitive process of an expert were shifted to multi - questions , one- stage assessment tests like sct , kf , scenario , puzzle with an emphasis over richness of illness scripts an expert has ( 4,14,37 - 64 ) . in the newest theory of clinical reasoning , known as the dual process , the expert is defined as a person who has both analytical and non - analytical thinking simultaneously ( 3 ) . based on the theory , clinical reasoning is not a completely analytical or non - analytical mental process . the physicians ' reasoning can be intuitive and/or analytical based on their experience and the kind of clinical condition they encounter . in other words , the clinical reasoning is on a continuum , with one extreme being intuitive thinking and the other analytical thinking ( 63,64 ) . this understanding of clinical reasoning concept shows that every physician owns both types of reasoning and the extent to which he employs each depends upon the clinical situation he / she encounters . the expert physician is more successful than a novice in using any of these types of reasoning . that is because of the accuracy of decisions he / she makes in the two dimensions of diagnosing and managing the illness , apart from the type of reasoning he / she adopts ( 63,64 ) . it seems that accepting the concept of expertise in the combined theory of clinical reasoning has two considerable impacts on the tests differentiating expert from novice : evaluating analytical clinical reasoning skill in experts is as important as the non - analytical clinical reasoning skill in novices . the clinical reasoning tests must be designed in a way that can evaluate both the accuracy of test answers and the individuals ' ability in appropriate switching between the two types of analytical and non - analytical reasoning . one way to accomplish this claim might be designing tests which can evaluate both kinds of reasoning . accordingly , instead of designing one single test with twofold application , a suggestion is to select a set of tests covering both analytical and non - analytical reasoning . therefore , each individual 's clinical reasoning skill can be evaluated by this set of tests at the same time . this suggestion has been also supported by recently published studies in the field of evaluation which have highlighted the importance of reaching a holistic picture of an expert s skills ( 65 - 67 ) . this has been a shift in clinical reasoning assessment from " one instrument for a skill " to " multi - instrument for all dimensions of a skill ( 3,31,34,68 - 70 ) . along the same line , early studies showed that designing a battery of tests may be useful to assess all aspects of clinical reasoning skill . however it has not yet received much attention in the medical education literature except few ones ( 1,61,71 - 73 ) . multi instrument approach and dual process both demonstrate that clinical reasoning skill should be evaluated from multiple sources , because neither single instrument approach nor each of mentioned approaches are able to provide an appropriate framework for " multiple biopsy " in evaluation ( 3 ) . this leads to an approach in which tries to propose a method for evaluating all aspects of clinical reasoning skill rather than developing one single best instrument . however , administering such tests requires an appropriate study to determine which existing test is analytic - induced and which one is not . it should be noted that the presupposition here is that we agree that the clinical reasoning test format determines whether a test is analytical or non - analytical induced , while in some studies on reflective practice , the type of assignment given to the individuals in a simulated clinical situation can determine the dimension of their reasoning ( 74,75 ) .
exploration into the concept of " medical expert " dates back to more than 50 years ago , yet yielding three leading theories in the area of clinical reasoning , namely , knowledge structure , hypotheticdeductive , and dual process . each theory defines " medical expert " in a dissimilar way . therefore , the methods of assessment through which the experts are identified have been changed during the time . in this paper , we tried to categorize and introduce some widely used tests for identification of experts within the framework of existing main theories . implementation of the proposed categorization for providing future assessment tools is discussed .
a 44-year - old man , who had a medical history of panic disorder , visited another hospital due to dyspnea on mild exertion . a coronary angiography showed a single coronary artery originating from the right coronary ostium . a single coronary artery bifurcated into the right coronary artery and left main coronary artery . the left main coronary artery coursed between the main pulmonary artery and aorta before bifurcating into the left descending artery and circumflex artery . we thought that panic symptoms or dyspnea on exertion might be a sign of myocardial ischemia due to compression of the left main coronary artery by the pulmonary artery and aorta . we decided that surgical treatment was the best option due to the high risk of sudden death associated with a coronary anomaly . under general anesthesia we dissected the left main coronary artery between the aorta and the main pulmonary artery on the beating heart . the proximal left main coronary artery was bifurcated from a single coronary artery that originated from the right coronary sinus . under cardiopulmonary bypass , only one coronary ostium was observed in the right coronary sinus , and a single coronary artery originated from the ostium . a 5-mm arteriotomy was made to the left main coronary artery at the site in which the left coronary ostium should have been located . neo - ostium formation was performed with a 5-mm puncher in the left coronary sinus . anastomosis between the neo - ostium and the left main coronary arteriotomy site was performed using a 7 - 0 prolene continuous running suture ( fig . the aortic cross clamping time was 88 minutes , and total cardiopulmonary bypass time was 117 minutes . follow - up computed tomographic angiography before discharge showed good patency of the neo - ostium in the left coronary sinus without stenosis at the anastomosis site ( fig . the patient remained asymptomatic without any complications or events for 15 months after the surgery . angelini reviewed 1,950 coronary angiographies and reported that the incidence of right coronary artery originating from the left coronary sinus was 0.92% and vice versa was 0.15% , with a total incidence of 1.07% . patients are usually asymptomatic . however , it may cause angina , syncope , and even life - threatening complications such as myocardial infarction or ventricular fibrillation . thus , we must consider surgical treatment or intervention if signs of myocardial ischemia are present . several surgical techniques can be utilized to treat coronary anomalies , such as coronary reimplantation to the original sinus , coronary artery bypass graft ( cabg ) , pulmonary artery translocation , unroofing , and neo - ostium formation . in this case , the left main coronary artery was bifurcated from a single coronary artery originating in the right coronary sinus . furthermore , the left main coronary artery passed between the pulmonary artery and aorta to reach the left heart . cabg , coronary reimplantation , unroofing or neo - ostium formation could therefore have been considered as viable surgical options . coronary reimplantation is one of the most physiologically beneficial repairs , but is technically difficult , and stenosis may occur at the site of anastomosis . cabg is technically feasible , but the arterial conduit has a competitive flow problem if no stenotic lesions are present on the natural coronary artery . also , a vein conduit may be problematic if the patient is young because of long - term patency . however , extended unroofing may cause valve insufficiency if the anomalous coronary artery is located under the valve commissure . unroofing was not proper for our case because a separated left main coronary artery originated from a single coronary artery , not the right coronary sinus . neo - ostium formation in the left coronary sinus without unroofing was considered to be a proper surgical treatment in this case . successful surgical treatment of anomalous of coronary anomaly depends on expertise in anatomic and hemodynamic pathophysiology , in addition to the selection of the appropriate surgical treatment option . we report that this case was successfully treated with neo - ostium formation in anomalous origin of the left coronary artery from the right coronary system .
anomalous origin of a coronary aortic artery is a rare cardiac anomaly . although it can cause angina , syncope , and palpitations , most patients are asymptomatic . this anomaly requires surgical treatment or intervention because it is associated with sudden death . several surgical techniques , such as coronary reimplantation , coronary artery bypass grafting ( cabg ) , unroofing , and neo - ostium formation , have been proposed as treatments . we report a case surgically treated with neo - ostium formation in anomalous origin of the left coronary artery from the right coronary sinus .
enterococcus faecalis can form a calcified biofilm in tough environmental conditions within the root canals . biofilm formation on tissues and biomaterial surfaces can lead to biofilm - mediated infections , which are difficult to treat as a result of the increased antimicrobial resistance of biofilm bacteria . the adherence of bacteria to a solid surface forms the initial and the most important step in the formation of biofilm . e. faecalis possess different virulence factors that enable them to adhere to dentin and invade dentinal tubules . enterococci also express factors that aid their adhesion to host cells and extracellular matrix , which in turn facilitates tissue invasion , causes immunomodulation and produces toxin mediated damage . the e. faecalis collagen binding protein , ace and a serine protease , targets the extracellular matrix proteins of host cells and allows adherence to type i collagen . sodium hypochlorite ( naocl ) is one of the most commonly used endodontic irrigant because of its ability to destroy a broad spectrum of microbes , but it has some undesirable characteristics such as tissue toxicity , allergic potential , and disagreeable taste , which has prompted researchers to look for other alternatives . the literature has shown that various natural plant extracts , a source of bioactive compounds has antimicrobial , and therapeutic effects suggesting its potential to be used as an endodontic irrigant . literature has shown that neem has antimicrobial and therapeutic effects suggesting its potential to be used as an endodontic irrigant . murray et al . also suggested that morinda citrifolia ( mc ) juice can be formulated for use as an intracanal irrigant . evaluated green tea ( gt ) to be safe , having antioxidant , anti - inflammatory , and radical scavenging activity , which is an advantage over the traditional root canal irrigants . the aim of this study was to study the effects of various herbal extracts namely mc ( noni ) , azadiracta indica ( ai ) ( neem ) and gt as a final rinse on the adherence of e. faecalis to root canal dentin using the confocal laser scanning microscopy ( clsm)-based bacterial adherence assay . a pre - existing collection of donated human teeth was used after ethics institutional review board approval . fifty non - carious single - rooted teeth maintained in phosphate - buffered saline ( pbs ) solution were used . the crown was decoronated at the level of cementenamel junction and the apical 3 mm were ground using a diamond rotary bone - cutting saw ( marterials science , nw ltd . , settle , england , uk ) to obtain uniform root sections of about the 8-mm length . the tooth specimens were then vertically sectioned with microtome to obtain a thickness of 50 microns . fresh plants of mc , ai and gt ( yucca enterprise , mumbai ) were powdered and prepared for extraction . a weighed quantity of 500 g of the powdered herbal plants were macerated with 500 ml of 99% ethanol and filtered using a double filter paper and then centrifuged at 10,000 rpm for 20 min . it was stored at 4c until required . a dilution assay was first performed in order to determine the minimum inhibitory concentrations of the phytochemical extracts . e. faecalis growth was determined by the presence of turbidity in different concentrations and the minimum inhibitory concentration was determined to be 0.33 mg / ml for ai , gt and 1.25 mg / ml for mc . one colony of e. faecalis american type culture collection ( atcc 29212 ) was raised in tryptone bile x - glucuronide agar ( merck ) and was transferred to 50 ml of all culture media ( sigma aldrich , st . louis , mo ) . the culture was allowed to grow overnight under stationary aerobic conditions at 37c . the prepared teeth ( n = 50 ) were divided randomly into 5 groups of 10 each . all the specimens were treated with 5.25% naocl for 30 min followed by 5 mmol / l ethylenediaminetetraacetic acid ( edta ) for 5 min and the final irrigants to be tested were used for 30 min . in group 1 specimens , specimens , 5.25% naocl was used as the final irrigant . in group 3 specimens , mc was used as the final irrigant . in group 4 specimens , ai was used as the final irrigant and in group 5 , gt was used as the final irrigant . the dentin blocks were inoculated with 200 l of e. faecalis ( 10 cells / ml colony - forming units ) at 37c for 1 h. after the incubation period , the root canals of dentin blocks were washed with 1 ml of pbs to remove any non - adherent bacteria of the root canal walls . the dentin specimens were carefully spread onto a microscope slide and stained with baclight ( invitrogen , molecular probes , carlsbad , ca ) and examined in a clsm ( carl zeiss , oberkochen , germany ) , which were set to monitor fluorescein isothiocyanate and propidium iodide . the baclight stain has two fluorescent dyes , fluorescein isothiocyanate and propidium diode with emission of 480/500 nm and 490/635 nm respectively . photographs were produced on a sony 5200 mb video printer ( sony corp , tokyo ) . total of nine fields were examined for each treatment , and the bacteria presented were counted . the nine fields were made up of three fields each from three similarly treated samples , inoculated by bacteria from the same culture . only bacteria in focus of each optical section were counted and were carried out carefully by one operator using a manual digital counter . the results of the bacterial adherence assay were determined statistically by one - way analysis of variance with post - hoc tukey . a pre - existing collection of donated human teeth was used after ethics institutional review board approval . fifty non - carious single - rooted teeth maintained in phosphate - buffered saline ( pbs ) solution were used . the crown was decoronated at the level of cementenamel junction and the apical 3 mm were ground using a diamond rotary bone - cutting saw ( marterials science , nw ltd . , settle , england , uk ) to obtain uniform root sections of about the 8-mm length . the tooth specimens were then vertically sectioned with microtome to obtain a thickness of 50 microns . fresh plants of mc , ai and gt ( yucca enterprise , mumbai ) were powdered and prepared for extraction . a weighed quantity of 500 g of the powdered herbal plants were macerated with 500 ml of 99% ethanol and filtered using a double filter paper and then centrifuged at 10,000 rpm for 20 min . a dilution assay was first performed in order to determine the minimum inhibitory concentrations of the phytochemical extracts . e. faecalis growth was determined by the presence of turbidity in different concentrations and the minimum inhibitory concentration was determined to be 0.33 mg / ml for ai , gt and 1.25 mg / ml for mc . one colony of e. faecalis american type culture collection ( atcc 29212 ) was raised in tryptone bile x - glucuronide agar ( merck ) and was transferred to 50 ml of all culture media ( sigma aldrich , st . louis , mo ) . the culture was allowed to grow overnight under stationary aerobic conditions at 37c . the prepared teeth ( n = 50 ) were divided randomly into 5 groups of 10 each . all the specimens were treated with 5.25% naocl for 30 min followed by 5 mmol / l ethylenediaminetetraacetic acid ( edta ) for 5 min and the final irrigants to be tested were used for 30 min . in group 1 specimens , specimens , 5.25% naocl was used as the final irrigant . in group 3 specimens , mc was used as the final irrigant . in group 4 specimens , ai was used as the final irrigant and in group 5 , gt was used as the final irrigant . the dentin blocks were inoculated with 200 l of e. faecalis ( 10 cells / ml colony - forming units ) at 37c for 1 h. after the incubation period , the root canals of dentin blocks were washed with 1 ml of pbs to remove any non - adherent bacteria of the root canal walls . the dentin specimens were carefully spread onto a microscope slide and stained with baclight ( invitrogen , molecular probes , carlsbad , ca ) and examined in a clsm ( carl zeiss , oberkochen , germany ) , which were set to monitor fluorescein isothiocyanate and propidium iodide . the baclight stain has two fluorescent dyes , fluorescein isothiocyanate and propidium diode with emission of 480/500 nm and 490/635 nm respectively . photographs were produced on a sony 5200 mb video printer ( sony corp , tokyo ) . total of nine fields were examined for each treatment , and the bacteria presented were counted . the nine fields were made up of three fields each from three similarly treated samples , inoculated by bacteria from the same culture . only bacteria in focus of each optical section were counted and were carried out carefully by one operator using a manual digital counter . the results of the bacterial adherence assay were determined statistically by one - way analysis of variance with post - hoc tukey . the histogram depicting the bacterial count for different treatment groups is shown in figure 1 . using one way anova with multiple comparison , significantly less bacteria were found adhering to the samples treated with ai followed by naocl , gt , mc , saline . there were conspiously high numbers of bacteria on dentin when saline ( 86.70% ) was used . ai treatment produced the maximum reduction in adherence of e. faecalis to dentin ( 9.30% ) followed by naocl ( 12.50% ) , gt ( 27.30% ) , mc ( 44.20% ) and saline ( 86.70% ) . clsm images of collagen membranes treated with the different groups and inoculated with bacteria are shown in figures 26 . percentage of adherent enterococcus faecalis remaining in dentin after different final irrigant treatment adherence of enterococcus faecalis after using saline as final irrigant ( a 10 ; b 40x magnification ) adherence of enterococcus faecalis after using sodium hypochlorite as final irrigant ( a 10 ; b 40x magnification ) adherence of enterococcus faecalis after using neem as final irrigant ( a 10 ; b 40x magnification ) adherence of enterococcus faecalis after using morinda citrifolia as final irrigant ( a 10 ; b 40x magnification ) adherence of enterococcus faecalis after using green tea as final irrigant ( a 10 ; b 40x magnification ) adherence is considered to be the first step for bacterial colonization of host tissue , including tubule invasion . the strain of e. faecalis has shown an ability to infect dentinal tubules , to tolerate high ph and to survive in obturated canals . these dentinal tubule walls may be a selective site for bacterial adherence and alteration of dentine components may influence the colonization . thus , for the adherence study , human tooth roots were split longitudinally to expose tubule surfaces for clsm analysis . after root canal treatment , residual bacteria reseed the chemically treated root - canal dentine and makes use of dentin to adhere and survive tough environmental conditions . naocl are known to be cytotoxic to tissues and a need for replacement with a more biocompatible irrigant is necessitated . pharmacological studies acknowledged the value of medicinal plants as a potential source of bioactive compounds . mc , ai , and gt have a broad range of antimicrobial activity and has been suggested as a natural endodontic irrigating solution . this study highlighted on the adherence capability of e. faecalis to dentin after the use of these 3 herbals as final irrigants . in order of adherence of e. faecalis to dentin , the most to least effective irrigants are : ai , naocl , gt , mc , and saline . the negative control group with saline was the least effective irrigating solution . the presence of active constituents such as nimbidin , nimbin , nimbolide , gedunin , azadirachtin , mahmoodin , margolone , and cyclictrisulphide contributes to the antibacterial activity of ai . this resulted in its anti - adherence activity by altering the bacterial adhesion and the ability of the microorganism to colonize thereby causing maximum reduction in adherence of e. faecalis to dentin . the antimicrobial action of gt might be attributed to its flavonoid content by inhibition of bacterial enzyme gyrase by binding to adenosine triphosphate b sub unit . mc , commercially known as noni has a broad range of therapeutic effects including antibacterial , antifungal , antiviral , antitumor , antihelminthic , analgesic , hypotensive , anti - inflammatory , and immune enhancing effects . the antibacterial property is due to the antibacterial components l - asperuloside and alizarin , which might be the reason for the antibacterial property . although ai , gt and mc exhibited antibacterial activity , ai showed relatively lesser adherence of e. faecalis to dentin . the major advantages of using herbal alternatives are easy availability , cost - effectiveness , increased shelf life , low toxicity , and lack of microbial resistance reported so far . this may be due to the fact that neem elaborates a vast array of biologically active compounds that are chemically diverse and hinders the vitality of the bacteria by inhibiting the respiratory chain . hence , the medicinal and antimicrobial properties of the plant ai can be an alternative to naocl as a final root canal irrigation . within the limitation of these experiments , we conclude that ai is effective in preventing adhesion of e. faecalis to dentin confirming the great potential of bioactive compounds and are useful for rationalizing the use of this plant as an endodontic irrigant . in vivo data may be helpful in determining the real potential usefulness of this plant for the treatment of root canal infections .
aim : the aim of this study was to assess the antibacterial efficacy of three different herbal irrigants against enterococcus faecalis.materials and methods : single rooted teeth were extracted due to orthodontic and periodontal reasons . the teeth were then inoculated with e. faecalis . the teeth were randomly divided into three experimental groups and two control groups of six samples each . group 1 specimens were treated with 5.2% sodium hypochlorite ( naocl ) for 30 min followed by 5 mmol / l ethylenediaminetetraacetic acid ( edta ) for 5 min and saline as final irrigant . group 2 specimens were treated with and 5.2% naocl for 30 min as final irrigant . group 3 were treated with morinda citrifolia ( mc ) for 30 min as final irrigant . group 4 were treated with azadiracta indica ( ai ) as final irrigant . group 5 were treated with green tea ( gt ) for 30 min as final irrigant . the dentin specimens were carefully spread onto a microscope slide and stained with baclight and examined in a confocal laser scanning microscope set to monitor fluorescein isothiocyanate and propidium iodide . a total of nine fields were examined for each treatment and the bacteria presented were counted.statistical analysis : using the one - way anova with multiple comparison , significantly less bacteria were found adhering to the samples treated with neem followed by naocl , gt , mc , saline.results:ai treatment produced the maximum reduction in adherence of e. faecalis to dentin ( 9.30% ) followed by naocl ( 12.50% ) , gt ( 27.30% ) , mc ( 44.20% ) and saline ( 86.70%).conclusion : neem is effective in preventing adhesion of e. faecalis to dentin .
probing the universality of the stellar initial mass function ( imf , i.e. , the distribution of the masses of stars at their birth ) , is one of the most challenging issues in modern astrophysics . the shape of the imf and its potential dependence on the environment are crucial to almost all branches of modern astrophysics ranging from planetary science , the evolution of stellar clusters , the dynamics and chemical enrichment of the interstellar medium , and galactic evolution . one of the first attempts to determine the shape of the imf was made by salpeter ( 1955 ) who derived the mass function of nearby galactic field stars of masses @xmath2 and found that it is well described by a power law @xmath3 , where @xmath4 is the number of stars between @xmath5 and @xmath6 and with @xmath7 . miller & scalo ( 1979 ) constructed the mass function of stars in the solar neighborhood and fitted it with a log - normal function with a steeper - than salpeter slope in the high mass regime ( i.e. , @xmath8 ) . they also extended the imf to the low mass regime and found the numbers of solar and sub - solar mass stars to fall below the expectations of the extrapolated salpeter mass function . scalo ( 1986 ) combined galactic field stars with ob associations and obtained a mass function which is also steeper than the salpeter mass function ( i.e , @xmath8 ) for @xmath9 m@xmath10 ( see also rana 1987 ) . a three component power - law fit of the galactic field mass function has been proposed by kroupa et al . ( 1993 ) , scalo ( 1998 ) and kroupa ( 2001,2002 ) whereas chabrier ( 2003 ) suggested that the galactic field stellar mass function can be fitted by a lognormal distribution for masses @xmath11 m@xmath12 and by the salpeter mass function for @xmath13 m@xmath12 . bochanski et al . ( 2010 ) constructed the mass function of 15 million low - mass stars ( @xmath14 ) and suggested it can be well represented by a log - normal function which peaks at @xmath15 m@xmath10 . hollenbach et al . ( 2005 ) and more recently parravano et al . ( 2011 ) proposed that the galactic field mass function is well described by a single functional form across the entire range of stellar masses which is a rosin - rammler function tapered by a salpeter - like power - law . other authors have proposed other functional forms such as the product of a power law and an exponential function ( larson 1998 ) , and an order-3 logistic function ( maschberger 2013 ) . the mass function of stars that can be counted in the field of the galaxy includes stars with a wide spread in age , that have various metallicities , and that were formed in regions of potentially differing properties . in contrast , stars in clusters have roughly the same age , metallicity , and are located at the same distance . thus , one can presume that their observed present day mass functions ( pdmfs ) are a fair representation of their imfs especially in the case of young clusters in which the effects of stellar and dynamical evolution are minimal . the imf have been constructed for a large number of clusters in the galaxy and in the magellanic clouds including open clusters ( massey et al . 1995 ; massey & hunter 1998 ; massey 1998 ; sanner & geffert 2001 ; slesnick et al . 2002 ; piskunov et al . 2004 ; moraux et al . 2004 ; gouliermis et al . 2005 ; pandey et al . 2007 ; sharma et al . 2008 ; silva - villa et al . 2008 ; bouvier et al . 2008 ; liu et al . 2009 ; boudreault et al 2010 ; baker et al . 2010 ; casewell et al . 2011 ; wang et al . 2011 ; lodieu et al . , 2011 ) , globular clusters ( paresce & de marchi 2000 ; de marchi et al 2010 ; paust et al . 2010 ) , and young clusters and stellar associations ( massey et al . 1989 ; massey & thompson 1991 ; massey & johnson 1993 ; parker et al . 1992 ; hillenbrand et al . 1993 ; oey 1996 ; hillenbrand 1997 ; herbig 1998 ; sirianni et al . 2000,2002 ; bjar et al . 2001 ; muench et al . 2002 ; preibisch et al . 2002 ; liu et al . 2003 ; luhman 2000,2004a , b,2007 ; luhman et al . 1999;2003a,2003b,2009 ; selman & melnick 2005 ; prisinzano et al . 2005 ; oliveira et al . 2005,2008 ; leistra et al . 2005,2006 ; levine et al . 2006 ; massi et al . 2006 ; schmalzl et al . 2008 ; sung et al . 2008 ; andersen et al . 2008 ; harayama et al . 2008 ; espinoza et al . 2009 ; scholz et al . 2009 ; sung & bessel 2010 ; campbell et al . 2010 ; salas & cruz - gonzlez 2010 ; ojha et al . 2010 ; delgado et al . 2011 ; bayo et al . 2011 ; gennaro et al . 2011 ; da rio et al . 2012a ; alves de oliveira et al . 2012 , tripathi et al . 2014 , mallick et al . the derivation of the shape of the pdmf in these studies relied on constructing the histogram of stellar masses ( or of their logarithmic values ) in bins of equal sizes and then fitting it with one or several functional forms . a minimization of the chi - square of the fit then allows for the derivation of the fit parameters and their associated uncertainties . in the intermediate- to high mass regimes , the values of the slope derived using this approach vary in the range between @xmath16 and @xmath17 when stellar masses are binned logarithmically . it is often claimed in the literature that , within the @xmath1 uncertainty , the derived values are broadly consistent with the salpeter slope . however , this is far from being clear . an inspection of the derived values of the slope in the this mass regime for several clusters for which identical data reduction algorithms and theoretical evolutionary tracks have been used to derive the stellar masses does suggest that the slopes of the imf for these clusters do not overlap within the @xmath1 uncertainty level ( e.g. , massey 2011 ; sharma et al . 2008 ; lata et al . 2010 ; tripathi et al . 2014 ) . deriving the slopes / shape of the imf in different mass regimes using binned data is not without problems . one major issue is the dependence of the derived slopes on the size of the bin , particularly when dealing with low number statistics ( maz apellniz & beda 2005 ) . maz apellniz & beda ( 2005 ) also showed that the use of uniform size bins in mass or the logarithm of the mass can bias the determination of the slope of the imf when using a @xmath18 minimization of the binned data . the origin of the bias lies in the correlation between the number of stars per bin and the weights assigned to each bin . they showed that these biases can be reduced by using bins of variable sizes which contain equal numbers of stars . however , a potential danger of this method is to smooth features in the imf ( e.g. , bumps of physical origin ) by forcing stars to be distributed in bins containing equal numbers of stars . another important limitation of fitting binned mass functions is the undesired effect of the subjective choice of break points ( i.e. , the points where the mass functions turns from one power law / functional form to another ) . in this work , we use a bayesian statistics approach to infer the parameters that characterize the shape of the pdmf / imf for a number of young stellar clusters when the underlying imf is assumed to be described by the tapered power law function , a lognormal function at low masses coupled to a power law function at higher masses , and a three - component power law function . allen et al . ( 2005 ) applied a bayesian analysis in order to infer the slope of the low mass end of the galactic field imf . however , the observational data did not allow them to distinguish between a single power law , a two - segment power law , or a lognormal function . olmi et al . ( 2014 ) used a similar approach to infer and compare the parameters describing the shape of the mass function of submillimeter clumps in two _ herschel infrared galactic plane survey _ fields . weisz et al . ( 2013 ) used mock data to quantify the uncertainties associated with the inference of the high mass slope of the imf by bayesian methods , as a function of the number of stars in the cluster and the range of stellar masses involved . they used this to argue that the uncertainties on the slopes of the imf at the high mass end derived using standard least square fitting methods tend to be generally underestimated . in . [ models ] , we write down the three imf models we intend to compare the observational data with . in . [ observations ] , we briefly present and discuss the basic features of the observational data we employ for a number of young clusters . the bayesian inference method is presented in . [ bayesian ] . the inter - cluster comparison for each of the considered imf models in presented in . [ intercluster ] and an inter - model comparison for each cluster is presented in . [ intermodel ] . in . [ completeness ] the effects of completeness and uncertainties on stellar masses are presented . in . [ discussion ] we discuss some of the issues related to variations in the imf , and in . [ conclusions ] , we conclude . , @xmath19m@xmath10 , @xmath20 ) for three clusters with a number of stars @xmath21 , @xmath22 , and @xmath23 and for masses in the range [ 0.02 - 150 ] m@xmath10 . the drawn masses for each cluster are binned using logarithmic bins with sizes of @xmath24=0.1(left panel ) , @xmath25 ( middle panel ) , and @xmath26 ( right panel ) . over - plotted to each binned mass function ( full black line ) is the parravano et al . imf with the fiducial galactic field values of the imf parameters . ] uncertainty of the imf parameters on the bin - size for three clusters with a number of stars @xmath21 , @xmath22 , and @xmath23 . the stellar masses are from the parravano et al . ( 2011 ) field imf ( i.e. , the ones shown in fig . [ fig3 ] ) and the values and uncertainties of the imf parameters are derived using a standard @xmath18 minimisation technique . the figure shows clearly the dependence of the uncertainties on the adopted bin size . ] some of the most commonly used functional forms in the literature to describe the imf are a multi - component power law function ( kroupa 2001,2002 ) , a lognormal distribution for masses @xmath27 m@xmath10 complemented with a salpeter slope for masses @xmath28 m@xmath10 ( chabrier 2003,2005 ) , and a tapered power - law function ( de marchi et al . 2010 , parravano et al . 2011 ) . the sets of parameters that define the galactic field imf in each of the models ( below ) refer to a system imf , that is , when the census of stars is uncorrected for unresolved binary stars . parravano et al . ( 2011 ) applied the tapered power - law imf ( hereafter referred to as par ) to the galactic field observations of reid et al ( 2002 ) . they found that the system imf can be described by : @xmath29\ } , \label{eq1}\ ] ] where @xmath30 is a normalisation constant and @xmath20 , @xmath19 m@xmath10 , and @xmath31 . chabrier ( 2005 ) combined data in the v - band from reid et al . ( 2002;2004 ) and k - band data from henry & mccarthy ( 1990 ) to construct the galactic field imf which he parametrized as ( referred to in the text as chab ) : @xmath32 where @xmath33 is a normalization constant , @xmath34 m@xmath10 , @xmath35 m@xmath10 , @xmath36 , and @xmath37 m@xmath10 . finally the multi - component power law imf s described by ( kroupa 2002 ; weidner & kroupa 2004 , referred to in the text as kr ) : @xmath38 with @xmath39 m@xmath10 , @xmath40=0.5 m@xmath10 , @xmath41 , @xmath42 , and @xmath43 . [ cols="<,^,^,^,^,^ , < " , ] _ orion nebula cluster _ : the orion nebula cluster ( onc ) located at a distance of @xmath44 pc from the sun , is the nearest cluster which hosts a number of massive b and o stars . a census of the stellar content of the onc has been performed by several groups ( hillenbrand 1997 ; palla & stahler 1999 ; hillenbrand & carpenter 2000 ; slesnick et al . 2004 ; andersen et al . 2011 ) . in this work , we use the most recent determination of stellar masses in the onc obtained by da rio et al . ( 2012b ) . these authors used the wide field imager ( wfi ) located at the 2.2 m mpg / eso telescope at la silla . the field of view of the wfi is large enough ( @xmath45 ) to encompass the entire onc in one pointing . their photometry included measurement in the i - band and two medium band filters at @xmath46 and @xmath47 nm . from the colours obtained in these three bands , they were able to derive the effective temperatures of 1750 sources and place them on the hertzsprung - russel ( hr ) diagram . the masses ( and ages ) were derived using the evolutionary tracks of baraffe et al . ( 1998 ) and dantona & mazzitelli ( 1998 ) . since da rio et al . ( 2012b ) could not assign masses and ages for about 25 % of the sources when using the baraffe et al . tracks as these are located above the 1 myrs isochrone , we use in the work the masses they have derived using the dantona & mazzitelli ( 1998 ) evolutionary tracks . we complemented the da rio et al . ( 2012b ) data by the census of massive stars ( in total 27 stars missing from the da rio et al . 2012b data ) in the onc obtained by hillenbrand ( 1997 ) . da rio et al . ( 2012b ) reported the presence of a contamination by a background population in the onc and therefore , we discard stars that have a membership probability of belonging to the onc that is @xmath48 . the total remaining sample is composed of @xmath49(onc)@xmath50 . the mass range of stars in this sample is [ 0.029 - 45.7 ] m@xmath10 . hillenbrand et al . ( 2013 ) used spectroscopic measurements and derived the spectral type and stellar masses for 619 onc stars . out of these , the spectral types for 437 stars were compared to the photometric spectral types of da rio et al . ( 2012b ) . as discussed in hillenbrand et al . ( 2013 , section 5.2 and fig . 10 in their paper ) , the scatter between the spectroscopically determined spectral type and the ones determined by da rio et al . ( 2012b ) is of the order of 1.75 spectral sub - class . these variations are small enough such as not to induce any significant variation in the derived stellar masses . it is important to note that the census of stars in the onc is also very likely contaminated by a significant foreground population as recently shown and discussed by alves & bouy ( 2012 ) and bouy et al . _ @xmath0 ophiuchi _ : several groups have investigated over the past two decades the census of stars in this young star forming region ( e.g. , rieke et al . 1989 ; luhman & rieke 1999 ; williams et al . 1995 ; erickson et al . 2011 ) . using wircam , alves de oliveira et al . ( 2010 ) performed a comprehensive census of the stellar content in @xmath0 ophiuchi . they confirmed many of their sources using a follow - up spectroscopic study and complemented it with spectroscopically confirmed sources from studies by other groups ( wilking et al . 2008 ; mcclure et al . 2010 ; geers et al . 2010 ; erickson et al . 2011 ) . in total , 250 spectroscopically confirmed members of the cluster were placed on the h - r diagram ( alves de oliveira et al . 2012 ) . in this work , we make use of the sample of sources that is complete ( with @xmath51 ) and with this choice , the number of sources is reduced to @xmath49(@xmath0 oph)@xmath52 . stellar masses were derived using the baraffe et al . ( 1998 ) and siess et al . ( 2000 ) evolutionary tracks and assuming a distance to the cluster of 130 pc . the masses of the stars considered in this sample extend over the mass range [ 0.033 - 7.22 ] m@xmath10 . _ taurus _ : a census of the protostellar and stellar population in the taurus star forming region has been performed by luhman ( 2000 ) , brice@xmath53o et al . ( 2002 ) , luhman et al . ( 2003b ) , luhman ( 2004a ) , and scelsi et al ( 2007,2008 ) . the most recent available information concerning this cluster is provided by luhman et al . these authors performed spectroscopy on infrared sources that have been identified in the clouds with the xmm-_newton _ extended survey of the taurus molecular cloud ( xest , gdel et al . 2007 ) and the taurus spitzer survey ( rebull et al . 2010 ) . the masses and ages of members of taurus were estimated using the theoretical evolutionary tracks of chabrier et al . ( 2000 ) for m@xmath12/m@xmath54 , the baraffe et al . ( 1998 ) tracks for @xmath55 m@xmath12/m@xmath56 , and palla & stahler ( 1999 ) for m@xmath12/m@xmath57 . available proper motion observations were also used by luhman et al . ( 2009 ) in order to put additional constraints on the membership of the sources to the taurus cluster . in total , the newest census of luhman et al . ( 2009 ) contain @xmath58 spanning the mass range [ 0.012 - 3 ] m@xmath10 . _ cha i _ : the stellar content of the chamaleon i star forming region ( cha i ) has been investigated by mamajek et al . ( 2000 ) , song et al ( 2004 ) , luhman et al . ( 2004b ) , lyo et al . ( 2006 ) , and mu@xmath59i et al . ( 2011 ) . using optical and near - infrared photometry with follow up spectroscopy , luhman ( 2007 ) presented a census of the stellar population of cha i ( 226 sources ) . out of these 226 known members , 11 were excluded due to very uncertain spectral types . in order to ensure for a better completeness , luhman ( 2007 ) imposed a limit of @xmath60 and @xmath61 for the two distinct stellar concentrations / clusters in the cha i star forming regions ( cha i south and cha i north , respectively ) . this reduced the number of known members to 85 and 34 in cha i south and cha i north , respectively . the masses of the stars were derived , as for taurus , using the stellar evolutionary tracks of chabrier et al . ( 2000 ) for m@xmath12/m@xmath54 , baraffe et al . ( 1998 ) for @xmath62 m@xmath12/m@xmath56 and palla & stahler ( 1999 ) for masses m@xmath12/m@xmath57 . in this work , we consider the population of cha i south . the masses of the stars found in cha i south fall in the range [ 0.009 - 2.6 ] m@xmath10 . _ ic 348 _ : the ic 348 cluster is located at a distance of 310 pc and its estimated age is @xmath63 myr ( e.g. , stelzer et al . 2012 ) . its stellar content has been investigated by lada & lada ( 1995 ) , najita et al . ( 2000 ) , muench et al . ( 2003 ) , preibisch et al . ( 2003 ) , burgess et al . ( 2009 ) , and alves de oliveira et al . ( 2013 ) . in this work , we use the stellar census obtained by luhman et al . ( 2003a ) . cluster membership was determined by placing the stars ( 268 ) on an extinction corrected diagram of @xmath64 versus @xmath65 and @xmath66 versus @xmath65 . spectra were obtained for these 268 stars . as for cha i and taurus , luhman et al . ( 2003a ) used the stellar evolutionary tracks of chabrier et al . ( 2000 ) , baraffe et al . ( 1998 ) , and palla & stahler ( 1999 ) to derive the masses and ages of the stars for masses in the ranges @xmath67 , @xmath68 and @xmath69 , respectively . luhman et al . ( 2003a ) then defined an imf - sample of stars by selecting only members that have @xmath70 . this reduced the number of members to @xmath49 ( ic 348)@xmath71 , which is the sample of stars we adopt in this work . the masses of the stars in this sample extend over the range [ @xmath72 m@xmath10 . _ ngc 2264 _ : investigations of the stellar content of the young ( 2 - 4 myrs ) cluster ngc 2264 has been performed by flaccomio et al . ( 1999 ) , park et al . ( 2000 ) , and sung et al . sung et al . ( 2008,2010 ) measured the masses of stars in ngc 2264 from photometric observations . they constructed a color - magnitude diagram ( @xmath73 versus @xmath74 ) of cluster members and derived their masses by comparing them to the stellar evolutionary models of baraffe et al . ( 1998 ) and siess et al . they measured the masses of stars in the locus of the pre - main sequence ( pms ) of ngc 2264 , using a mean reddening function . heavily embedded stars and stars below the pre - main sequence were excluded . this reduced the sample of cluster members with which sung et al . ( 2012 ) constructed the ( binned ) imf of ngc 2264 to @xmath49(ngc 2264)@xmath75 . this is the sample of stars in ngc 2264 that is considered in this work . the masses of the stars considered in this sample span over the range [ @xmath76 m@xmath10 . _ ngc 6611 _ : the stellar content and the imf of ngc 6611 have been investigated by several groups ( e.g. , walker 1961 , sagar 1979 , bonatto 2006 ) . in this work , we use the sample of cluster members whose masses have been derived by oliveira et al . ( 2009 ) for the low mass populations in the cluster using observations from the _ hubble space telescope_. this is complemented by the census of more massive stars derived from ground - based observations by oliveira et al . oliveira et al . ( 2009 ) constructed the cmd of the cluster and derived two distinct samples of masses for the cluster members by assuming ages of 2 and 3 myrs . these were derived using the 2 and 3 myrs isochrones of baraffe et al . ( 1998 ) ( for lower masses ) and siess et al . ( 2000 ) ( for higher stellar masses ) . in this work , we have considered a single sample of @xmath49(ngc 6611)@xmath77 stars and have calculated the mass of each star as being the mean of the 2 and 3 myrs mass estimates . _ ngc 2024 _ : ngc 2024 is a young , very embedded cluster ( e.g. , comeron et al . 1996 ; haisch et al . 2000 ) . the only publicly available and documented catalogue of members of ngc 2024 is presented in levine et al . the sample of stars in this catalogue is however restricted to the mass range [ 0.02 - 0.72 ] m@xmath10 . levine et al . ( 2006 ) combined near infrared spectroscopic observations with @xmath78 photometry . they derived the stellar masses and ages of the stars from the h - r diagram using the baraffe et al . ( 1998 ) evolutionary tracks . despite the fact that the data of ngc 2024 is limited to the substellar regime , we still include it in our sample of clusters and take it as an example of the effects of `` missing data '' on the inference of the parameters that describe the underlying imf . [ fig1 ] and fig . [ fig2 ] display a binned form of the imf for each of these cluster . the bins are of equal logarithmic sizes of @xmath79 ( red lines ) and @xmath80 ( yellow lines ) . overlaid to the imf of each cluster and for each choice of the logarithmic mass bin size are the galactic field star imf of parravano et al . ( 2011 ) ( bottom panels ) , chabrier ( 2005 ) ( middle panels ) , and kroupa ( 2002 ) ( top panels ) with their fiducial parameters given in . [ models ] . by performing only a visual inspection of the mass functions of the eight clusters displayed in fig . [ fig1 ] and fig . [ fig2 ] , it is difficult to assess any variations in the parameters that describe their underlying imf . it is also equally difficult to assess which imf model is a better description for the underlying imf of each individual cluster . the classical method that is commonly employed to infer the parameters that describe the shape of the imf is a minimization of the @xmath18 between the data and and imf model . as pointed by several authors ( maz apellniz & beda 2005 ; weisz et al . 2013 ) , both the values of the parameters describing the underlying imf of a stellar cluster as well as the uncertainties on these parameters are dependent on the choice of bin size . an additional complication is created by the somewhat arbitrary and subjective choice of the mass range over which a functional form of the imf is fitted , particularly in the presence of break points such as in the case of the chabrier and kroupa imfs . the dependence of the derived parameters of the imf on the bin size is further illustrated in fig . [ fig3 ] and fig . [ fig4 ] . [ fig3 ] displays binned imfs of 3 clusters with @xmath21 , @xmath22 , and @xmath23 ( yellow , red , and black respectively ) and where the masses , which are randomly sampled from the parravano et al . imf ( eq . [ eq1 ] ) in the mass range [ 0.02 - 150 ] m@xmath10 , are binned using equals size logarithmic mass bins of @xmath81 ( left panel ) , @xmath82 ( middle panel ) , and @xmath83 ( right panel ) . the binned mass functions are then fitted with the tapered power law imf ( de marchi et al . 2010 ; parravano et al . the parameters @xmath84 , @xmath85 , and @xmath86 are derived by minimizing the @xmath18 between the fit function and the binned imfs using a levenberg - marquart algorithm . [ fig4 ] displays the @xmath1 uncertainty , in the form of a percentage , on @xmath84 ( top panel ) , @xmath85 ( middle panel ) , and @xmath86 ( lower panel ) as a function of the logarithmic bin size ( in the range @xmath87 ) , and for the three clusters with @xmath21 ( yellow ) , @xmath22 ( red ) , and @xmath23 ( black ) . the figure clearly shows that the uncertainty on the derived parameters is bin - dependent and that it increases with the increasing size of the bin . the use of bayesian statistics for the inference of the parameters that describe the underlying shape of the imf of a given stellar cluster with resolved populations makes it possible to avoid the pitfalls that can be caused by these subjective choices . in bayesian statistics , assessing the probability that a specific model @xmath88 out of a set of possible models @xmath89 ( i.e. , a specific combination of the model s parameters ) can explain a set of data @xmath90 is given by the fundamental equation ( i.e. , bayes theorem ; bayes 1763 ) : @xmath91 where @xmath92 is the posterior probability ( hereafter the _ posterior _ ) that the model @xmath93 is correct given the data @xmath94 , @xmath95 is the prior probability ( hereafter the _ prior _ ) that is assigned to the model s veracity based on our current understanding of the physical processes that govern the systems the model aims at explaining , and @xmath96 is the the probability of obtaining the data @xmath94 given the model @xmath93 . the term in the denominator of eq . [ eq4 ] is a normalization factor ( called the @xmath97 ) and is given by the summation over all possible models ( i.e. , summation over the different ranges of each of the model s parameters ) @xmath98 . this ensures that the sum of all posterior probabilities equals unity , i.e. , @xmath99 . the specific problem we are concerned with in this work is the underlying distribution function of stellar masses in stellar clusters . if the model @xmath93 can be described by a set of @xmath4 parameters @xmath100_{i}$ ] , and the data with an ensemble of stellar masses @xmath101 $ ] of @xmath102 measured values @xmath103 , then the posterior probability of the model is given by : @xmath104_{i}|\left[m_{\star}\right]\right)=\frac{p\left(\left[\theta_{n}\right]_{i}\right)~p\left(\left[m_{\star}\right ] |\left[\theta_{n}\right]_{i}\right)}{\sigma_{i } p\left(\left[\theta_{n}\right]_{i } \right ) p\left(\left[m_{\star}\right ] |\left[\theta_{n}\right]_{i})\right)}. \label{eq5}\ ] ] note that it is not necessary to calculate the evidence for comparisons of the relative probabilities of different sets of model parameters . the total likelihood of the ensemble of @xmath49 measurements is given by the product of the likelihood of each measured value : @xmath105 | \left[\theta_{n}\right]_{i}\right)= \prod_{j=1}^{n_{\star } } p\left(\left[m_{\star , j}\right ] | \left[\theta_{n}\right]_{i}\right ) \label{eq6}\ ] ] the prior reflects our knowledge about the physical processes that govern the values of the different parameters that describe the model . in this work we consider three distinct likelihood functions for the imf and which are given by the tapered power - law mass function ( de marchi et al . 2004;2010 ; parravano et al . 2011 ; eq . [ eq1 ] ) with its 3 parameters ( @xmath84 , @xmath85 , and @xmath86 ) , the lognormal+power law imf ( chabrier 2005 ; eq . [ eq2 ] ) which is described with four parameters ( @xmath106 , @xmath107 , @xmath108 , @xmath109 ) and the three - component power law function ( kroupa 2002 ; eq . [ eq3 ] ) with its five parameters ( @xmath110 , @xmath111 , @xmath112 , @xmath113 , @xmath40 ) . we sample the posterior probability distribution with a markov chain monte carlo ( mcmc ) algorithm . the mcmc method provides a robust approach to characterize the density of samples ( mcmc steps ) around discrete parameters sets in the multi - dimensional parameter space . the regions with the highest density of samples correspond to regions of the parameter space with the highest probability ( e.g. , gelman et al . 1996 ) . in this work , we use an mcmc algorithm based on the metropolis - hastings ( m - h ) method ( metropolis et al . 1953 ; hastings 1970 ) . in the m - h algorithm , a random walk is performed in the parameter space from an initial , user defined position . the choice of the initial position as well as of the step size in each of the parameters can be done using an informed guess ( i.e. , for example in our case by looking at the binned imfs ) , and/or through a `` burning phase '' in which the ability of the chain to converge around regions of high probability is tested . starting from a position @xmath100(l)$ ] in the parameter space , a new proposed value of the parameters @xmath100(p)$ ] is evaluated at the next step of the chain . the new proposed position has a probability density that depends only on the current position @xmath114(p)|[\theta_{n}](l))$ ] ( we use here a symmetric uniform function such that @xmath115(p)|[\theta_{n}](l))=q([\theta_{n}](l)|[\theta_{n}](p)$ ] ) and it is accepted , and replaced with the probability : @xmath116(p);[\theta_{n}](l))={\rm min}\left[1,\frac{p([\theta_{n}](p)|[m_{*}])}{p([\theta_{n}](l)|[m _ { * } ] ) } \frac{q([\theta_{n}](l)|[\theta_{n}](p)}{q([\theta_{n}](p)|[\theta_{n}](l)}\right ] . \label{eq7}\ ] ] it has been shown that the ideal acceptance rate for a one - dimensional gaussian distribution is @xmath117 and @xmath118 for a multi - dimensional gaussian target distribution ( gelman et al . 1997 ; roberts et al . 1997 ) . in this work , we optimize the step size in each of the parameters in order to maintain an acceptance rate of @xmath118 . this should not however be understood as a very strict requirement since some of the inferred posterior distributions of the parameters are not strictly gaussians ( see below ) . for clusters with a small number of stars ( @xmath49 ) such as ngc 2024 , we tolerate an acceptance rate of up to @xmath119 . in the following , we infer the posterior probability distribution function ( ppdf ) of the parameters that describe the underlying imf for the eight clusters considered in this study , and for the three likelihood functions described in . [ models ] . for each imf model , we apply the method first to synthetic data in order to assess the ability of the method to recover the set of parameters . [ fig5 ] displays an example of the the 1-d ppdf inferred for the parameters @xmath84 , @xmath85 , and @xmath86 as well as the 2-d posterior probability density in the ( @xmath120 ) , ( @xmath121 ) , and ( @xmath122 ) spaces for a sample of four synthetic clusters with @xmath21 ( top left panel ) , @xmath123 ( top right panel ) , @xmath22 ( bottom left ) , and @xmath23 ( bottom right ) . the @xmath124 , @xmath125 , @xmath22 , and @xmath23 stars of these clusters have been randomly sampled from the tapered power law imf ( eq . [ eq1 ] ) in the mass range [ 0.02 - 150 ] m@xmath10 with the galactic field values of the parameters ( @xmath126 ) . the dashed lines in the 1-d distributions and the white crosses in the 2-d distributions mark the position of these values in fig . [ fig5 ] . in the 2-d posterior probability density maps , the black , red , and orange closed contours enclose 68.27 % , 95.45 % and 99.73 % ( i.e. , the 1- , 2- and @xmath127 confidence levels ) of the posterior probability , respectively . in this work , we assume ( both for the synthetic clusters and the real data ) that we know little about the most probable value of each of the parameter . as prior probabilities on each of the parameters , we use a rectangular function given by : @xmath128)= \end{array } \left\ { \begin{array}{l } 1 ; a_{n } \leq \theta_{n } \leq b_{n } \\ \epsilon ; \theta_{n } < a_{n } , \theta_{n } > b_{n } , \\ \end{array } \right . \label{eq8}\end{aligned}\ ] ] where @xmath129 is an infinitely small quantity and where @xmath130 and @xmath131 are chosen in such a way as to bracket a large range for each of the parameters . in the inference shown in fig . [ fig5 ] , the values that we have used for [ @xmath132 are [ @xmath133 , [ @xmath134 , [ @xmath135 ( except for ngc 2024 where these values are [ @xmath136 , [ @xmath137,[@xmath138 ) , for the parameters @xmath84 , @xmath85 , and @xmath86 , respectively . the quantities @xmath139 , @xmath140 , and @xmath141 that are show for each value of @xmath49 are the mean values ( and these are not necessarily similar to the most probable values ) of the parameters and are shown along with the @xmath1 uncertainty which is calculated directly from the list of values of each parameter in the mcmc chain . [ fig5 ] clearly shows that the mcmc algorithm is able to recover with a very high efficiency the values of the parameters with which the data has been generated . the figure also displays the correlations that exist between these parameters ( i.e. , @xmath85 and @xmath86 increase and decrease with increasing values of @xmath84 , while @xmath85 decreases with increasing values of @xmath86 ) . we now turn to the real clusters taurus , cha i , ic 348 , onc , @xmath0 ophiuchi , ngc 2264 , ngc 6611 , and ngc 2024 . we follow the same procedure as for the case with the synthetic data . in this work , the adopted concept of universality is one in which the ppdfs of each of the parameters and for all clusters will overlap at the @xmath1 confidence limit . this corresponds to the same confidence limit that is used for comparing the values of the parameters when fitting the binned form of the imf . [ fig6 ] displays the contours that enclose @xmath142 of the posterior probability density ( i.e. , at the @xmath1 confidence level ) for each cluster . the black dashed line in the 1-d figures and the black crosses in the 2-d ones mark the position of the values of the parameters for the milky way field stars imf inferred by parravano et al . ( 2011 ) . several aspects of fig . [ fig6 ] are worth commenting on . as reported in studies of the imf using binned data for taurus and its more massive counterpart ngc 6611 ( luhman 2007 ; oliveira et al . 2009 ) , these two clusters stand out as having a steeper slope in the intermediate - to - high mass regime . the ppdf of their @xmath84 parameter peaks around values @xmath143 and the ppdf of their characteristic mass @xmath85 also peaks at larger values ( 0.7 - 0.8 m@xmath10 ) . the inferred posterior distributions of the parameters for ngc 2024 display a resemblance to those of taurus and ngc 6611 but the inferred ppdfs for this cluster ( i.e. , large values of @xmath84 and @xmath85 ) can be understood as being the result of the absence of high mass stars in the data . however , fig . [ fig6 ] also shows that the cases of taurus and ngc 6611 are not exceptions among the other clusters . not only are the ppdfs of the inferred parameters @xmath84 , @xmath85 , and @xmath86 not centered around the field imf values , they also show little or no - overlap between these clusters at the 1@xmath144 level ( note that the ppdf of @xmath84 for ngc 2024 and of @xmath86 for the onc are shifted by factors of -2 and -3 purely for presentation purposes ) . the onc presents another case of strong deviation from the galactic field imf with the peak of the ppdf for the @xmath86 parameter located at @xmath145 . this striking deviation has already been noted by da rio et al . ( 2012 ) who has argued that the steep slope of the onc at the low mass end can not result from incompleteness effects in this mass regime . the 1-d ppdfs and the 2-d posterior density maps shown in fig . [ fig6 ] strongly suggest that there is _ no universal set of parameters that characterizes the imf of young clusters _ and that the imf of individual clusters can deviate , in different mass regimes , from the galactic field imf . the mean values of the parameters along with the @xmath1 uncertainties , shown in fig . [ fig6 ] , confirm the absence of a global overlap between the parameters of these 8 clusters at the @xmath1 confidence limit . the dispersion among these mean values is @xmath146 for @xmath84 , @xmath147 for @xmath86 ( @xmath148 when excluding the onc ) , and @xmath149 for @xmath85 . whether there is an underlying function from which these values are drawn remains open . it is however impossible to answer this question with a sample consisting of only 8 clusters , as the frequency of each of these mean values among the larger population of galactic stellar clusters is not yet established . in order to visualize examples of the imf constructed using accepted sets of the inferred parameters , we show in fig . [ fig7 ] an over - plot of 12 imfs constructed using selected , and uncorrelated sets of the parameters ( @xmath150 ) from the mcmc chain to the binned imfs for each of the clusters . the inter - cluster comparison of the ppdfs of the inferred parameters that describe a tapered power law imf clearly highlight the existence of variations among the imf of these clusters . however , it is also relevant to explore the degree of variations among these clusters when the likelihood function has other functional forms . here , we explore the universality of the imf of these clusters by employing a likelihood function that is given by the combined - power law function ( chabrier 2005 ) . the functional form of this imf is given by eq . [ eq2 ] and it possesses four parameters which are the slope at the high mass end , @xmath106 , the width of the lognormal distribution , @xmath108 , the characteristic mass , @xmath107 , and the break point , @xmath109 , which marks the position at which the transition occurs between the lognormal and the power - law parts of the imf . however , only three of these parameters are independent and the value of @xmath109 can be calculated from any combination of @xmath106 , @xmath108 , and @xmath107 ( see appendix a for details ) . as in . [ tapered ] , we start by testing the mcmc algorithm on sets of synthetic clusters . the lower right panel in fig . [ fig8 ] displays the imfs in binned form of three synthetic clusters with @xmath151 , and @xmath152 and for which the individual stellar masses have been randomly sampled using the combined lognormal - power law imf in the mass range [ 0.02 - 150 ] m@xmath10 with the values of the parameters that correspond to the field star imf ( chabrier 2005 ) . an over - plot of the chabrier ( 2005 ) imf is also shown for comparison . [ fig8 ] also displays the inferred 1-d ppdfs and the 2-d posterior probability density maps for the parameters @xmath106 , @xmath107 , @xmath108 , and @xmath109 using the mcmc algorithm . for the inference of these ppdfs , we use rectangular functions ( i.e. , eq . [ eq8 ] ) for the priors on @xmath106 and @xmath108 with [ @xmath153=[0.25,3 ] and [ @xmath154 , respectively . we also include a prior on @xmath107 and @xmath109 by requiring that @xmath155 , with @xmath156 and @xmath157 . overall , the recovery process of the parameters is quite robust with the peak of the ppdf of the different parameters being distributed around the values with which the data was generated within the @xmath1 uncertainty interval . we note however a tendency for the ppdfs to deviate from a gaussian function and for the ppdf of @xmath109 to peak below the real value for clusters with the lowest numbers of stars , @xmath158 . the inference of the same parameters for the eight real clusters that are considered in this work is displayed in fig . as for the tapered - power law function , the colored contours associated with each of these clusters encloses @xmath142 of the probability in the 2-d posterior probability density maps . similar prior functions have been used here as for the synthetic clusters . however , for the onc , we had to reduce the ranges of the rectangular function in order to guarantee a @xmath159 acceptance rate and we required that @xmath160 , @xmath108 , @xmath161 , and @xmath162 . for ngc 2024 , we only infer the ppdf of @xmath108 and @xmath107 and choose rectangular prior functions for these parameters with @xmath163=[0.05,1.2]$ ] and [ 0.05,1.5 ] , respectively . the inferred ppdfs are consistent with those obtained in . [ tapered ] . the ppdfs of @xmath107 and @xmath106 of taurus and ngc 6611 peak at higher values than those of the other clusters , and while the ppdfs of some of the parameters for some of the clusters are broad enough to overlap with those of other clusters ( e.g. , the @xmath106 ppdfs of the taurus and cha i clusters ) , a global overlap between the ppdfs of the parameters of the clusters is not observed within the @xmath1 uncertainty level . the ppdfs are rather distributed around their values for the galactic field stars imf . at least for this sample of clusters , there is no indication that the parameters that describe their imf are universal . as with the the case of the tapered power low function , the mean values of the parameters along with the @xmath1 uncertainties reported in fig . [ fig9 ] also confirm the absence of a global overlap among the parameters of the 8 clusters considered in this study . for a consistency check , [ fig10 ] displays an over - plot of 12 imfs constructed using selected and uncorrelated sets of the parameters ( @xmath164 , @xmath109 ) from the mcmc chain to the binned imf for each of the clusters . we complete this section by inferring the ppdfs of the parameters that describe the imf when the likelihood function is given by the multi - component power law function imf ( i.e. , eq . [ eq3 ] ) . this functional form of this imf possesses five parameters . these are the slopes of the power laws that describe the imf in the low- , intermediate- , and high - mass ranges , @xmath110 , @xmath111 , and @xmath112 , respectively , as well as @xmath113 , and @xmath40 which are the two break points that mark the transition from one power law to another . only four of these parameters are independent ( e.g. , @xmath110 , @xmath111 , @xmath112 , and @xmath113 ) , and the fifth parameter ( @xmath40 ) along with the normalization can be derived using the constraints given by the total number of stars and the total mass of the cluster ( see appendix b for details ) . the lower right panel in fig . [ fig11 ] displays the binned form of the imf for three synthetic clusters ( with @xmath165 , @xmath22 , and @xmath152 ) where the individual masses have been sampled from the kroupa ( 2002 ) imf with the fiducial galactic field values . the galactic field kroupa imf is over - plotted to the binned imfs . [ fig11 ] also shows the inferred 1-d ppdfs and 2-d posterior probability density maps of the parameters for these synthetic clusters . as with the other imf models , the recovery process of the parameters is robust with the peaks of the ppdfs of the different parameters being distributed around the values with which the data was generated . the inferred 1-d ppdfs and 2-d posterior density distributions of the parameters for the real clusters is displayed in fig . [ fig12 ] . the prior functions that were adopted for the different parameters are rectangular functions for @xmath110 , @xmath111 , and @xmath112 . the values of the step sizes in each of the parameters are chosen such that , within the limits of the adopted rectangular prior function of each of these parameters , the acceptance rate in the mcmc chains is maintained at @xmath166 . the boundaries of the rectangular prior distribution for @xmath110 were selected to fall in the range @xmath167 $ ] , those of @xmath111 in the range @xmath168 $ ] , and those of @xmath112 fall in the range @xmath169 $ ] . we further imposed that @xmath170 , and @xmath171 where @xmath172 is the minimum stellar mass found in each cluster and with @xmath173 and @xmath174 falling in the range [ @xmath175 and [ @xmath176 for the different clusters , respectively . an exception to this is the case of the onc in which we imposed @xmath177 , @xmath178 , @xmath179 , @xmath180 , and @xmath181 . here also , the ppdfs of @xmath113 and @xmath112 for taurus and ngc 6611 are shifted to higher values with respect to the other clusters . the onc also shows distinct ppdfs for several parameters ( @xmath110 , @xmath111 , and @xmath40 ) . note that the ppdf of @xmath111 for the onc has been shifted by + 7 for visualization purposes . while the pdpfs of @xmath110 , @xmath111 , and @xmath40 for the clusters ( cha i , ic 348 , @xmath0 ophiuchi , and ngc 2264 ) show a reasonable overlap , the ppdfs of their @xmath112 are distributed around the fiducial field value of @xmath43 and show a minimal level of overlap . for ngc 2024 , we have chosen here to infer the entire set of parameters in order to contrast it with the its inferred ppdfs which were restricted to the low - mass in . [ lognorm ] . [ fig12 ] shows that while the ppdfs of @xmath110 and @xmath113 for ngc 2024 are informative of the distribution of these parameters for this cluster , the ppdfs of of the other parameters that describe the high - mass end part are either very broad ( i.e. , for @xmath40 ) or flat ( i.e. , for @xmath111 , @xmath112 ) . as for the par and chab imf models , we show in fig . [ fig13 ] an over - plot of 12 imfs constructed using selected and uncorrelated sets of the parameters ( @xmath182 , @xmath40 ) from the mcmc chain to the binned imf for each of the clusters . and uncertainty on the mass @xmath183 . the probability of measuring each stellar mass given its the observed flux @xmath184 ( full red line ) is given by the product of the probability of the observed flux given the mass @xmath185 , @xmath186which is modeled by a lognormal probability function centered at @xmath185 and with a width @xmath183 ( blue triple dot - dashed line ) with a function that describes the prior probability of measuring a particular stellar mass which we take to be the mass function itself at each iteration of the mcmc chain ( black dashed line ) . ] in this section , we make use of the information obtained above in order to compare , for each individual cluster , the ppdfs of the parameters that are common between these models . the sole parameter that is common between the three imf models considered here is the slope in the intermediate - to - high mass end ( @xmath84 , @xmath106 , and @xmath112 for the par , chab , and kr imf models , respectively ) . [ fig14 ] displays the inferred 1-d ppdfs of @xmath84 , @xmath106 , and @xmath112 for each of the eight clusters considered in this work . with the exception of @xmath0 ophiuchi for which the ppdfs of @xmath84 , @xmath106 , and @xmath112 peak at the same location , the ppdfs of @xmath84 , @xmath106 , and @xmath112 for the remaining clusters highlight the differences between these clusters both in terms of the differences in the position of the peak value of the ppdf , their deviation from the common galactic field value of @xmath187 , as well as in terms of the width of the ppdfs of these parameters for each cluster , when their parameters are inferred using each of these models . in the sections above , we have used the entire currently available stellar content of each cluster in order to infer the ppdfs of the parameters that characterize its imf . in order to assess whether the mass functions for these clusters are truly representative of their imf , it is important to include the effects of completeness . the completeness is in general a function of several quantities such as stellar mass , spectral energy distribution class , location in the cluster , and local effects of extinction . it is also important to include the effects of the uncertainties on the estimated masses in the bayesian characterization of the shape of the imf . in addition to uncertainties in the photometry , other sources of uncertainty can affect the derived masses such as uncertainties on the distance of individual stars in the cluster , extinction , and the uncertainties associated with the stellar evolutionary tracks . the effects of mass uncertainties and completeness are not expected to affect the parameters with a high level of degeneracy since they affect the stellar masses differently in different mass ranges with the effects of completeness being more significant towards the low mass end , and the mass uncertainties being more significant for higher masses . both completeness and uncertainty on the mass are notoriously difficult to assess , and for the sample of clusters we are studying here , only the onc have uncertainty estimates for each stellar mass measurement and an individual star - by - star completeness probability ( see da rio et al . the high mass stars of the onc which are included into the onc stellar census using the hillenbrand ( 1997 ) data were associated a star - by - star completeness correction of 1 . for the other seven clusters , there are no star - by - star completeness correction estimates , nor measurements of the uncertainties on the individual stellar masses . however , for each cluster , the authors have provided a cut - off mass above which the census of stars in each cluster is assumed to be complete . the completeness limits for each of the clusters , @xmath188 , is reported in tab . [ tab1 ] . we illustrate the effects of completeness and mass uncertainties using the model imf with the smallest number of parameters which is the tapered power - law imf model ( eq . [ eq1 ] ; de marchi et al . 2010 ; parravano et al . 2011 ) . except for the onc which has a star - by - star mass uncertainty and completeness correction estimates , the other clusters considered in this work only have a cutoff mass above which the imf is presumed to be complete ( i.e. , the completeness function is those case is a step function whose value is unity for stellar masses @xmath189 , and zero otherwise ) . a completeness correction in the form of a cutoff is obviously not an entirely satisfying approach since it results in discarding away stars with an otherwise high individual completeness probability . in fig . [ fig15 ] , we show the effects of completeness using this approach on the 1-d ppdfs and 2-d posterior probability density of the inferred parameters of the imf for the seven clusters , taurus , cha i , ic 348 , @xmath0 ophiuchi , ngc 6611 , ngc 2264 , and ngc 2024 . the results in fig . [ fig15 ] should be contrasted with those shown in fig . [ fig6 ] for the same clusters without any completeness correction . the loss of information from the low - mass regime results in an overall broadening of the @xmath1 contour levels and 1-d ppdfs . the case of cha i is striking . the large value of @xmath148 m@xmath10 for the completeness limit for the cluster ngc 2264 also results in a broadening of the inferred 1-d ppdf of its parameters . [ fig16 ] displays the 1-d ppdfs and 2-d posterior probability densities of the parameters when a lognormal+power law is adopted as the likelihood function . a higher degree of overlap is observed between the parameters of the 7 clusters shown here at the @xmath1 confidence limit ( i.e. , up to 5 clusters in the @xmath190 parameter space ) . however , there is no global overlap between all clusters within the @xmath1 confidence interval . our previous conclusions remain however unaffected by applying this form of completeness correction for these clusters . the 1-d ppdfs and 2-d posterior probability densities show marginal overlap and are scattered on both sides of the fiducial values of the galactic field imf parameters . we now turn to the case of the onc . we construct a complete sample of stars for the onc using the star - by - star completeness probability provided by da rio et al . ( 2012b ) . for each star , a uniform probability value in the range [ @xmath191 ( @xmath192}$ ] ) is drawn and compared to the star s completeness probability @xmath193 . wherever @xmath194,\star}$ ] the star is added to the `` complete '' sample . the complete census of stars constructed using this approach is reduced to 1360 stars . [ fig17 ] compares the imf of the onc in its binned form with and without the completeness correction . proportionally , a larger number of low mass stars are removed from the stellar census after applying the completeness correction , leading to a narrower imf . this is reflected in the inferred ppdfs of the slopes of the mass function at low masses , @xmath86 , and intermediate- to high masses , @xmath84 , which peak both at higher values ( compare the full and dashed lines in fig . [ fig18 ] , onc versus onc - c ) . the effect of the completeness correction on the inferred ppdf of the characteristic mass is however minimal . in all of the results presented above , we have neglected the effect of the uncertainties associated with the individual stellar masses on the ppdfs of the inferred parameters , assuming implicitly that the measured masses are equal to their true values . in reality , the masses of stars can be affected by both observational uncertainties ( e.g. , instrumental uncertainties , and uncertainties on the distances of individual stars in a cluster ) and uncertainties associated with the conversion of observed quantities into masses using theoretical stellar evolutionary . the observed fluxes @xmath195 are compared to synthetic stellar fluxes that are constructed using chosen values of several quantities such as the stellar mass ( @xmath196 ) , effective temperature ( @xmath197 ) , surface gravity ( @xmath198 ) , metallicity ( @xmath199 ) , age @xmath200 , visual extinction ( @xmath201 ) , and other parameters / physical quantities that may ( or not ) be included in stellar evolutionary models ( i.e. , accretion rates in the pms phases , rotation , etc ) . for a star @xmath102 , this defines a probability for the star to have an observed flux @xmath202 given its physical quantities / parameters , @xmath203 . the probability of the observed flux given the mass @xmath185 , @xmath186 can be calculated by marginalizing over the other parameters / physical quantities . the required quantity is the probability that a star has a mass @xmath185 , given its observed fluxes @xmath184 . using the bayes theorem , this is given by : @xmath204 where @xmath205 is the prior probability function that characterizes the measurement of the stellar mass @xmath206 , and @xmath207 is a normalization factor . as in weisz 2013 ) , we use the stellar mass function as a prior on individual stellar masses , at each iteration in the mcmc chain . the likelihood probability of the parameters of the mass function , given the stellar mass @xmath185 , is thus given by : @xmath208 ) = \int_{m_{min}}^{m_{max } } p(f_{*,j}|m_{*,j } ) p(m_{*,j}|[\theta_{n}])dm , \label{eq10}\ ] ] and the likelihood probability of the parameters of the mass function , given the ensemble of stellar masses @xmath209 $ ] , is thus given by : @xmath210|[\theta_{n } ] ) = \prod_{j=1}^{n_{\star } } \int_{m_{min}}^{m_{max } } p(f_{*,j}|m_{*,j } ) p(m_{*,j}|[\theta_{n}])dm . \label{eq11}\ ] ] the posterior probability distribution of each of the model parameters ( in this case @xmath86 , @xmath84 , @xmath85 ) , given the stellar masses @xmath209 $ ] , , is then given by : @xmath211)=\prod_{j=1}^{n_{\star } } \int_{m_{min}}^{m_{max } } p(f_{*,j}|m_{*,j } ) p(m_{*,j}|[\theta_{n}])dm \nonumber \\ \times p(\gamma_{p } ) p(\gamma_{p } ) p(m_{p } ) . \label{eq12}\end{aligned}\ ] ] since the uncertainty on the mass can be due to the cumulative effects of uncertainties on the photometry , theoretical models , distances , and extinction , a reasonable assumption is to assume that the observed mass of each individual star can be described by a lognormal distribution . [ fig18 ] displays four examples of the effect the existence of uncertainties in the mass has on the of the likelihood function . the modified likelihood function is given by the product of the tapered power law imf ( here shown with its fiducial galactic field values of the parameters ) , and the lognormal distributions which are defined by their characteristic mass which is taken to be the observed stellar mass @xmath185 ( for star @xmath102 ) , and the width of the lognormal distribution is described by the measured @xmath1 uncertainty on the mass , @xmath183 . for most stars of the onc , da rio et al . ( 2012b ) provided an estimate of @xmath212 . the uncertainties reported by da rio et al . ( 2012b ) on individual masses ( and ages ) of the stars are obtained by propagating the errors on the luminosities and effective temperatures . for the massive stars of the onc which are not included in the da rio et al . census and which were taken from the hillenbrand ( 1997 ) data , we have assigned to those stars a conservative mass uncertainty of @xmath213 of their measured mass . this value sits at the upper end of the mass uncertainties measured by da rio et al . [ fig18 ] shows that the effect of including the uncertainties on stellar masses in the inference of the imf parameters leads to a steepening of the slope at the intermediate- to high mass end ( @xmath84 , compare onc and onc - u in fig . [ fig18 ] ) . this is expected since the inclusion of the imf as a prior on measured masses tends to shift the most likely masses of each star to lower masses in this mass regime whereas the effect is negligible for masses near the peak of the imf ( i.e. , see fig . [ fig19 ] ) . the effect of including the mass uncertainties has minimal effects on the shape and peak value of the ppdf of @xmath86 and @xmath85 . when both the completeness correction and mass uncertainties are included , the effect of shifting the peak of the ppdf of @xmath84 to higher masses is cumulative ( i.e. , red line and contours in fig . [ fig18 ] , case onc - c - u ) . the example presented here with the onc data highlights the importance of including the uncertainties on the mass in the inference of the ppdfs of the imf parameters . nonetheless , including the mass uncertainties has only significant effects on the ppdf of the slope in the intermediate- to high mass end ( @xmath84 ) and minimal effects on the other two parameters ( @xmath86 and @xmath85 ) . since we observe significant variations in the ppdfs of all the imf parameters among the clusters considered in this work ( fig . [ fig6 ] , fig . [ fig15 ] , and fig . [ fig18 ] for the tapered power law function with and without the completeness correction ) , we expect that the inclusion of mass uncertainties for the remaining seven clusters would not affect our conclusions on the existence of variations between the imf of these clusters . our findings are consistent with those of weisz et al . for realistic ranges of the uncertainties on the individual stellar masses ( up to @xmath214 applied across the entire considered mass range ) , weisz et al . ( 2013 ) found that the peak of the ppdf for the slope at the intermediate to - high mass range is shifted by a negligible amount ( @xmath215 dex ) up to @xmath216 dex with a decreasing dynamical mass range for the considered masses . their inferred ppdf of the slope of the power - law shows a greater sensitivity to the completeness correction in terms of the position of the most likely value . however , they show that as long as conservative estimates of the completeness correction function are considered ( i.e. , a step function above which the data is assumed to be @xmath217 complete and below which the data is discarded ) , the inferred ppdfs of the power - low slope peaks at the same position as the one with which the mock data was produced . our results here clearly point in the same direction as theirs . if including the completeness correction leads to an entirely complete sample , then the inferred slope of the mass function at the intermediate- to high mass regime reflects it true value . the debate over the shape of the imf , its universality or potential variation among stellar clusters , as well as the similarity between the imf in stellar clusters and the field stars imf has been ongoing ever since salpeter ( 1955 ) published his findings , and is perhaps approaching the level of myth ( melnick 2009 ) . it is beyond the scope of this paper to review all star cluster formation models . it is important however to mention that from a purely theoretical point of view much of the arguments in favor / disfavor of variations of the imf originate from the inclusion / absence in the models of the necessary physical processes that can lead to a significant degree of variations . a perfect illustration of this are the contrasting conclusions made by dib et al ( 2010 ) and hennebelle ( 2012 ) . dib et al . ( 2010 ) considered the case of accreting protostellar cores in a non - accreting star forming clump whereas hennebelle ( 2012 ) considered the case of non - accreting cores in an accreting clump . dib et al . ( 2010 ) showed that the accretion of gas by protostellar cores can lead to variations in the core mass function ( and hence of the imf ) when environmental conditions vary from clump - to - clump ( i.e. , for example when cores of the same mass have different lifetimes and accretion timescales in different environments ) . on the other hand , in the model of hennebelle ( 2012 ) , the accretion of gas by the clump from the larger scale environment is only expected to change the thermodynamical properties of the gas out of which newer generations of stars can form in the clump . as found by hennebelle ( 2012 ) and earlier pointed out by elmegreen et al . ( 2008 ) , the characteristic mass of the imf has an extremely weak dependence on the thermodynamical conditions out of which star form . the absence of accretion by the cores leaves the slopes at the high mass end and in the low mass regime unaffected . on the observational side , massey ( 2011 ) pointed out that much of the cluster - to - cluster variations can be due to the absence of spectroscopic measurements , the use of different reddening corrections , and different theoretical evolutionary tracks to convert luminosities into masses . he illustrated this by discussing the case of the ob association lh 58 in the lmc . for lh 58 , garmany et al . ( 1994 ) and massey ( 1998 ) derived slopes in the high mass end of @xmath218 and @xmath219 , respectively , using spectroscopy but different reddening corrections , and hill et al . ( 1998 ) obtained @xmath220 using photometric measurements only , while massey ( 1998 ) obtained @xmath221 using the garmany et al . ( 1994 ) photometric measurements with the hill et al . ( 1998 ) conversions from photometry to effective temperatures . at the low mass end , the case of the taurus cluster is often cited as a potential example whose mass function deviates from the field - like imfs ( luhman et 2000,2004a ) . goodwin et al . ( 2004 ) suggested that the observed deficit of low mass stars and brown dwarfs in taurus is due to the ejection of low mass cores by dynamical interaction while dib et al . ( 2010 ) and dib ( 2012 ) showed that a taurus - like mass function can be reproduced when protostellar cores continue to accrete over longer timescales ( i.e. , as a result of being supported by comparatively stronger magnetic fields ) , and thus depleting the population of very low mass cores and shifting the peak of the mass function towards higher masses . several works ( e.g. , stolte et al . 2006 ; espinoza et al . 2009 , hu@xmath222mann et al . 2012 ) have also reported that the slope of the imf at the high mass end of starburst clusters such as the arches cluster , ngc 3603 , and the quintuplet cluster might be shallower than the salpeter value , albeit in the particular case of the arches clusters , newer measurements have brought back the slope to a more agreeable degree with the salpeter value ( espinoza et al . 2009 ; habibi et al . dib et al . ( 2007,2008 ) and dib ( 2007 ) proposed that shallower - than salpeter slopes can result from the efficient coalescence of closely packed protostellar cores in a dense protocluster environment . hocuk & spaans ( 2011 ) have also reported that the characteristic mass of the imf can be shifted to higher values and that a shallower than - salpeter slope in the intermediate- to high mass regimes can be reproduced in environments where the gas is exposed to very high x - ray and cosmic ray fluxes . in this work , we have presented the first analysis of the universality of the stellar initial mass function ( imf ) using bayesian statistics with a monte carlo markov chain method for a sample of eight young galactic stellar clusters ( ic 348 , onc , ngc 2024 , ngc 6611 , ngc 2264 , @xmath0 ophiuchi , chameleon i , and taurus ) . those eight clusters were chosen based on the availability of their measured individual stellar masses . with the exception of the onc , individual masses where derived using the same theoretical evolutionary tracks , at least in the low mass end regime . we derive the posterior probability distributions ( ppdfs ) of the parameters that describe the imf all the way from the brown dwarfs and low mass regime up to the regime of massive stars . for each of the considered clusters , we infer the ppdf of the imf parameters when the likelihood function that describes the imf is given by a tapered power law function ( de marchi et al . 2010 ; parravano et al . 2012 ) , a lognormal distribution at low masses coupled to a power law at higher masses ( chabrier 2005 ) , and a multi - component power law function ( kroupa 2002 ) . the tapered power function has three parameters which are the slopes of the mass function at the low and intermediate- to high mass regimes ( @xmath86 and @xmath84 , respectively ) and the characteristic mass @xmath85 . the lognormal - power low function is described by four parameters which are the width of the lognormal distribution and its characteristic mass ( @xmath108 and @xmath107 , respectively ) , the slope of the power law component , @xmath106 , and the position of the break point between the lognormal and power law parts of the mass function , @xmath109 . the three - component mass function has five parameters which are the three slopes of the power law components ( @xmath223 , @xmath112 ) and the two break points that mark the transition from one power law to another . the inter - cluster comparison of the inferred 1d ppdfs as well as the 2d surface density probabilities of the parameters with the different likelihood functions ( @xmath224 ; [ @xmath225 , [ @xmath226 ) shows that these distributions do not overlap within the @xmath1 uncertainty level ( fig . [ fig6 ] , fig . [ fig9 ] , and fig . [ fig12 ] ) . when the likelihood function is the tapered power law mass function , the most likely values of @xmath86 span the range @xmath227 @xmath228 to @xmath229 with ngc 2024 and the onc possessing these two extreme values , respectively . the ppdfs of @xmath84 also show variations over a significant range going from @xmath230 for @xmath0 oph , ic 348 , and cha i , and up to @xmath231 for taurus and its most massive counterpart ngc 6611 . variations in the most likely value of the inferred ppdfs for @xmath85 also span a significant range from @xmath232 m@xmath10 for the onc and ic 348 and up to @xmath233 m@xmath10 for taurus and ngc 6611 . the inferred ppdf of @xmath85 which peaks at a much higher value of @xmath234 m@xmath10 should not be considered very seriously since the current census of stars for ngc 2024 and which we used in this work contains only low mass stars with a maximum mass of @xmath235 m@xmath10 . similar variations are observed when the likelihood functions that describes the imf is chosen to be the lognormal+power law function ( fig . [ fig9 ] ) or the multi - component power law function ( fig . [ fig12 ] ) . furthermore , the most probable values of the imf parameters for most of these clusters deviate substantially from their values for the galactic field stars imf . we have explored the effects of mass incompleteness on the inferred ppdfs of the imf parameters . the completeness correction whether performed using a star - to - star completeness probability ( available only for the onc ) , or by imposing a cutoff mass at the low mass end above which the mass function is assumed to be complete ( i.e. , for the remaining seven clusters ) affects essentially the inferred ppdfs of the slope of the mass function at the low mass end ( i.e. , compare the ppdfs of @xmath86 in fig . [ fig6 ] with those in fig . [ fig15 ] and fig . [ fig18 ] ) . we have also measured the effect on the inferred ppdfs of taking into account the uncertainties on the measured masses which we model as lognormal distributions . we also chose the imf itself ( at each iteration in the mcmc chain ) as a prior on the measured masses . this is performed here only for the case of the onc for which such uncertainties are available . our results ( fig . [ fig18 ] ) show that the inclusion of the mass uncertainties shifts the ppdf of the slope at the intermediate- to high mass end @xmath84 to higher masses , leaving the ppdfs of @xmath86 and @xmath85 unaffected . this is expected due to the combined effect that uncertainties on the stellar masses are higher for higher mass stars and the fact that the mass function has a negative slope in the high mass regime . the results presented in this paper highlight the importance of using advanced and robust statistical methods for the inference of the parameters that characterize the stellar initial mass function . we find that all of the three imf functional forms are able to reproduce the observations if the parameters that define each function are allowed to vary significantly ( i.e. , beyond the @xmath1 limit ) . however , it is not clear which one of these three functions , if any , captures the physics of the star formation process . in this work , we have inferred the parameters that strictly describe the `` shape '' of the imf . additional parameters can be included such as the mass of the cluster ( see e.g. , cervio et al . 2013 ) maximum stellar mass present in the cluster in the framework of a cluster mass - maximum stellar mass relation . since we are dealing here with only eight clusters with a small range in cluster masses , the significance of including @xmath236 as a free parameter in this study is rather limited . in this work , we have used rather simple prior functions on the parameters ( i.e. , rectangular functions ) , thus assuming implicitly that we have little knowledge on their parameters from theory and or theoretical models of star formation . at least for the eight clusters considered in this work , the posterior probability distribution functions derived for their parameters can serve as prior functions when using improved data from future surveys . the high sensitivity and angular resolution of the _ james web space telescope _ ( jwst ) will open entirely new and exciting perspective for the application of this method to a large set of galactic and extragalactic clusters with resolved stellar populations . i thank the referee for useful comments and suggestions . i enjoyed discussions on bayesian statistics with daniel mortlock and kaisey mandel . i am very grateful to kevin luhman , hwankyung sung , catarina alves de oliveira , nicola da rio , and joana oliveira for sharing their data and for useful information . i also thank sacha hony for a careful reading of the manuscript and useful suggestions . this work was supported by a marie - curie intra european fellowship under the european community s seventh framework program fp7/2007 - 2013 grant agreement no 627008 . allen , p. r. , koerner , d. w. , reid , i. n. , trilling , d. e. 2005 apj , 625 , 385 alves , j. , bouy , h. 2012 , a&a , 547 , 97 alves de oliveira , c. , moraux , e. , bouvier , j. , bouy , h. , marmo , c. , albert , l. 2010 , a&a , 515 , 75 alves de oliveira , c. , moraux , e. , bouvier , j. , bouy , h. 2012 , a&a , 539 , 151 alves de oliveira , c. , moraux , e. , bouvier , j. , et al . 2013 , a&a , 549 , 123 andersen , m. , meyer , m. r. , greissel , j. , aversa , a. 2008 , apj , 683 , l183 baker , d. , jameson , r. , casewell , s. et al . 2010 , mnras , 408 , 2457 baraffe , i. , chabrier , g. , allard , f. , hauschildt , p. 1998 , 337 , 403 bayes , t. phil . 1763 , 53 , 370 ( repodudec in : biometrika , 1955 , 45 , 293 ) bayo , a. , barrado , d. , stauffer , j. et al . 2011 , a&a , 536 , 63 bjar , v. j. s. , martn , e. l. , zapatero osorio , m . 2001 , apj , 556 , 830 bochanski , j. j. , hawley , s. l. , covey , k. r. , west , a. a. , reid , i. n. , golimowski , d. a. ; ivezi , z. 2010 , aj , 139 , 2679 bonatto , c. santo , j. f. c. , jr . , bica , e. 2006 , a&a , 445 , 567 boudreault , s. , bailer - jones , c. a. l. , goodman , b. , henning , t. , caballero , j. a. 2010 , a&a , 510 , 27 bouvier j. , kendall , t. , meeus , g. et al . 2008 , a&a , 481 , 661 bouy , h. , alves , j. , bertin , e. , sarro , l. m. , barrado , d. 2014 , a&a , 564 , 29 brice@xmath237o , c. , luhman , k. l. , hartmann , l. , stauffer , j. r. , kirkpatrick , j. d. 2002 , apj , 580 , 317 burgess , a. s. m. , moraux , e. , bouvier , j. , marmo , c. , albert , l. bouy , h. 2009 , a&a , 508 , 823 campbell , m. a. , evans , c. j. , mackey a. d. , gieles , m. , alves , j. eta l. 2010 , mnras , 405 , 421 casewell , s. , jameson , r. , burleigh , m. , et al . 2011 , mnras , 412 , 2071 cervio , m. , romn - ziga , c. , luridiana , v. , bayo , a. , snchez , n. , prez , e. 2013 , 553 , 31 chabrier , g. , baraffe , i. , allard , f. , hauschildt , p. 2000 , apj , 542 , l119 chabrier , g. 2003 , pasp , 115 , 763 chabrier , g. 2005 , in astrophysics and space science library , vol . 327 , the initial mass function 50 years later , ed . e. corbelli , f. palla , & h. zinnecker , 41 comeron , f. , rieke , g. h. , rieke , m. j. 1996 , apj , 473 , 294 dantona , f. , mazzitelli , i. 1998 , in brown dwarfs and extrasolar planets , eds . r. rebolo , e. l. martin , m. r. zapatero osorio , aspc , 134 , 442 da rio , n. , gouliermis , d. , rochau , b. , pasquali , a. , setiawan , j. , de marchi , g. 2012a , mnras , 422 , 3556 da rio , n. , robberto , m. , hillenbrand , l. a. , henning , t. , stassun , k. g. 2012b , apj , 748 , 14 delgado , a. j. , alfaro , e. , j. , yun , j. l. 2011 , a&a , 531 , 141 de marchi , g. , paresce , f. , portegies zwart , s. 2004 , in the initial mass function 50 years later , eds . e. corbelli , f. palla , and h. zinnecker , ap&ss , 327 , 77 de marchi , g. , paresce , f. , portegies zwart , s. 2010 . , apj , 718 , 23 dib , s. 2007 , jkas , 40 , 157 dib , s. , kim , j. , shadmehri , m. 2007 , mnras , 381 , l40 dib , s. , shadmehri , m. , gopinathan , m. , kim , j. , henning , th . 2008 , in massive star formation : observations confront theory , asp conf . series , ed . beuther , h. linz , t. henning , 387 , 282 dib , s. , shadmehri , m. , padoan , p. , maheswar , g. , ojha , d. k. , khajenabi , f. 2010b , mnras , 405 , 401 dib , s. 2012 , in the labyrinth of star formation , ed . d. stamatellos , s. goodwin , & d. ward - thompson ( springer ) , in press ( arxiv:1207.4982 ) elmegreen , b. g. , klessen , r. s. , wilson , c. d. 2008 , apj , 681 , 365 erickson , k. l. , wilking , b. a. , meyer , m. r. , robinson , j. g. , stephenson , l. n. 2011 , aj , 142 , 140 espinoza , p. , selman , f. j. , melnick , j. 2009 , a&a , 501 , 563 flaccomio , e. , micela , g. , sciortino , s. , favata , f. corbally , c. , tomaney , a. 1999 , a&a , 345 , 521 garmany , c. d. , massey , p. , parker , j. w. 1994 , aj , 108 , 1256 geers , v. , scholz , a. , jayawardhana , r. et al . 2011 , apj , 726 , 23 gelman , a. , roberts , g. o. , gilks , w. r. 1996 , proc . spie , 3338 , 371 gelman , a. , gilks , w. r. , roberts , g. o. 1997 , ann . appl . probab . 1997 , 1 , 279 gennaro , m. , brandner , w. , stolte , a. , henning , th . 2011 , mnras , 412 , 2469 goodwin , s. p. , whitworth , a. p. , ward - thompson , d. 2004 , a&a , 419 , 543 gouliermis , d. , brandner , w. , henning , t. 2005 , apj , 623 , 846 gdel , m. , briggs , k. r. , arzner , k. 2007 , 468 , 353 habibi , m. , stolte , a. , brandner , w. , hu@xmath222man , b. , motohara , k. 2013 , a&a , 556 , 26 haisch k. , e. , lada , e. a. , lada , c. j. 2000 , aj , 120 , 1396 harayama , y. , eisenhauer , f. , martins , f. 2008 , apj , 675 , 1319 hastings , w. k. 1970 , biometrika , 57 , 97 henry , t. j. , mccarthy , d. w. 1990 , apj , 350 , 334 herbig , g. h. 1998 , apj , 497 , 736 hennebelle , p. 2012 , a&a , 545 , 147 hill , r. j. , madore , b. f. , freedman , w. l. 1998 , apj , 429 , 192 hillenbrand , l. a. 1997 , aj , 113 , 173 hillenbrand , l. a. , massey , p. , strom , s. e. , merrill , k. m. 1993 , aj , 106 , 1906 hillenbrand , l. a. , carpenter , j. m. 2000 , apj , 540 , 236 hillenbrand , l. a. , hoffer , a. s. , herczeg , g. j. 2013 , aj , 146 , 85 hollenbach , d. , parravano , a. , mckee c. f. 2005 , in the initial mass function 50 years later , 327 , eds . e. corbelli & f. palla ( dordrecht : springer ) , 417 hocuk , s. , spaans , m. 2011 , a&a , 536 , 41 hu@xmath222mann , b. , stolte , a. , brandner , w. , gennaro , m. , liermann , a. 2012 , a&a , 540 , 57 kroupa , p. , tout , c. a. , gilmore , g. 1993 , mnras , 262 , 545 kroupa , p. 2001 , mnras , 322 , 231 kroupa , p. 2002 , science , 295 , 82 larson , r. b. 1998 , mnras , 301 , 569 lada , e. a. , lada , c. j. 1995 , aj , 109 , 1682 lata , s. , pandey , a. k. , kumar , b. , bhatt , h. , pace , g. , sharma , s. 2010 , aj , 139 , 378 leistra , a. , cotera , a. s. , liebert , j. , burton , m. 2005 , apj , 130 , 1719 leistra , a. , cotera , a. s. , liebert , j. 2006 , aj , 131 , 2571 levine , j. l. , steinhauer , a. , elston , r. j. , lada , e. a. 2006 , apj , 646 , 1215 liu , q. , de grijs , r. , deng , l. c. , hu , y. , baraffe , i. , beaulieu , s. f. 2009 , mnras , 396 , 1665 liu , w. m. , meyer , m. r. , cotera , a. s. , young , e. t 2003 , aj , 126 , 1665 lodieu , n. , dobbie , p. d. , hambly , n. c. 2011 , a&a , 527 , 24 luhman , k. l. , rieke , g. h. 1999 , apj , 525 , 440 luhman , k. l. 2000 , apj , 544 , 1044 luhman , k. l. , rieke , g. h. , young , e. t. , cotera , a. s. , chen , h. , rieke , m. a. , schneider , g. , thompson , r. i. 2000 , apj , 540 , 1016l luhman , k. l. , stauffer , j. r. , muench , a. a. , rieke , g. h. , lada , e. a. , bouvier , j. , lada , c. j. 2003a , apj , 593 , 1093 luhman , k. l. , brice@xmath237o , c. , stauffer , j. r. , hartmann , l. , barrado y navascus , d. , caldwell , n. 2003b , apj , 590 , l348 luhman , k. l. 2004a , apj , 617 , 1216 luhman , k. l. 2004b , apj , 602 , 816 luhman , k. l. 2007 , apj , 173 , 104 luhman , k. l. , mamajek , e. e. , allen , p. r. , cruz , k. l. 2009 , apj , 703 , 399 lyo , a .- r . , song , i. , lawson , w. a. et al . 2006 , mnras , 368 , 1451 maz apellniz , j. , beda , l. 2005 , apj , 629 , 873 mallick , k. k. , ojha , d. k. , tamura , m. , pandey , a. k. , dib , s. et al . 2014 , mnras , accepted , ( arxiv:1407.1987 ) mamajek , e. e. , lawson , w. a. , feigelson , e. 2000 , apj , 544 , 356 maschberger , t. 2013 , mnras , 429 , 1725 massey , p. , silkey , m. , garmany , c. d. , degioia - eastwood , k. 1989 , aj , 97 , 107 massey , p. , thompson , a. b. 1991 , aj , 101 , 1408 massey , p. , johnson , j. 1993 , aj , 105 , 980 massey , p. , johnson , k. e. , degioia - eastwood , k. 1995 , apj , 454 , 151 massey , p. 1998 , in the stellar insitial mass function , eds , g. gilmore , & d. howell ( san francisco : asp ) , vol 142 of asp conf . 17 massey , p. , hunter , d. a. 1998 , apj , 493 , 180 massey , p. 2011 , in the proceedings of up2010 : have observations revealed a variable upper end of the initial mass function ? m. treyer , t.k . wyder , j.d . neill et al . ( san francisco : asp ) , asp conf . ser 440 , p. 29 massi , f. , testi , l. , vanzi , l. 2006 , a&a , 448 , 1007 mcclure , m k. , furlan , e. , manoj , p. et al . 2010 , apjs , 188 , 75 melnick , j. 2009 , in a long walk through astronomy : a celebration of luis carrasco s 60th birthday , eds . e. recillas , a. luna , & y. d. mayya , revmexaa ( serie de conferencias ) , 37 , 21 moraux , e. , kroupa , p. , bouvier , j. 2004 , a&a , 426 , 75 metropolis , n. , rosenbluth , a. n. , rosenbluth , m. n. , teller , a. h. , teller , e. 1953 , j. che , . , 21 , 1087 miller , g. e. , scalo , j. m. 1979 , apjs , 41 , 513 muench , a. a. , lada , e. a. , lada , c. j. , alves , j. 2002 , apj , 573 , 366 muench , a. a. , lada , e. a. , lada , c. j. , et al . 2003 , aj , 125 , 2029 mu@xmath59i , k. , scholz , a. , geers , v. fissel , l. jayawardhana , r. 2011 , apj , 732 , 86 najita , j. r. , tiede , g. p. , carra , j. s. 2000 , apj , 541 , 977 oey , m. s. 1996 , apj , 465 , 231 ojha , d. k. , kumar , m. s. n. , davis , c. j. , grave , j. m. c. 2010 , mnras , 407 , 1807 oliveira , j. m. , jeffries , r. d. , van loon , j. th . , littlefair , s. p. naylor , t. 2005 , mnras , 358 , l21 oliveira , j. m. , jeffries , r. d. , van loon , j. th . 2009 , mnras , 392 , 1034 olmi , l. , angles - alczr , d. , elia , d. , molinari , s. , pestalozzi , m. , et al . 2014 , a&a , 564 , 87 palla , f. , stahler , s. w. 1999 , apj , 525 , 772 pandey , a. k. , sharma , s. , upadhyay , k. , ogura , k. , sandhu , t. s. , mito , h. , sagar , r. 2007 , pasj , 59 , 547 paresce , f. , de marchi , g. apj , 2000 , 534 , 870 park , b .- g . , sung , h. , bessell , m. s. , kang , y. h. 2000 , apj , 120 , 894 parker , j. w. , garmany , c. d. , massey , p. , walborn , n. r. 1992 , aj , 103 , 1205 paust , n. , reid , i. , piotto , g. et al . 2010 , aj , 139 , 476 parravano , a. , mckee , c. f. , hollenbach , d. j. 2011 , apj , 726 , 27 piskunov , a. e. , belikov , a. n. , kharchenko , n. v. , sagar , r. , subramanian , a. 2004 , mnras , 349 , 1449 powell , m. j. d. 1964 , computer j. 7 , 155 preibisch , t. , stanke , t. , zinnecker , h. 2003 , a&a , 409 , 147 preibisch , t. , brown , a. g. a. , bridges , t. , gunether , e. , zinnecker , h. 2002 , aj , 124 , 404 press , w. h. , teukolsky , s. a. , vetterling , w. t. , flannery , b. p. 2007 , numerical recipes : the art of scientific computing , third edition , 1235 ( new york : cambridge university press ) prisinzano , l. , damiani , f. , micela , g. , sciortino , s. 2005 , a&a , 430 , 941 rana , n. c. 1987 , a&a , 184 , 104 rebull , l. m. , padgett , d. l. , mccabe , c .- e . et al . 2010 , apjs , 186 , 259 reid , i. n. , gizis , j. e. , hawley , s. l. 2002 , aj , 124 , 2721 reid , i. n. , cruz , k. l. , allen , p. et al . 2004 , aj , 128 , 463 rieke , g. h. , ashok , n. m. , boyle , r. p. 1989 , apj , 339 , 71 roberts , g. o. , gelman , a. , gilks , w. r. 1997 , ann . , 7 , 110 sagar , r. , joshi , u. c. 1979 , ap&ss , 66 , 3 salas , l. , cruz - gonzlez , i. 2010 , revmexaa , 46 , 37 salpeter , e. e. 1955 , apj , 121 , 161 sanner , j. , geffert , m. 2001 , a&a , 370 , 87 scalo , j. m. 1986 , fundamentals of cosmic physics , 11 , 1 scalo , j. 1998 , in the stellar initial mass function , ed . g. gilmore , i. parry , s. ryan , cambridge : cambridge university press , p. 201 scelsi , l. , maggio , a. , micela , g. et al . 2007 , a&a , 468 , 405 scelsi , l. , sacco , g. , affer , l. et al . 2008 , a&a , 490 , 601 schmalz , m. , gouliermis , d. a. , dolphin , a. e. , henning , t. 2008 , apj , 681 , 290 scholz , a. , geers , a. jayawardhana , r. , fissel , l. , lee , e. , lafreniere , d. , tamura , m. 2009 , apj , 702 , 805 selman , f. j. , melnick , j. 2005 , a&a , 443 , 851 sharma , s. , pandey , a. k. , ogura , k. , aoki , t. , pandey , k. , sandhu , t. s. , sagar , r. 2008 , aj , 135 , 1934 siess , l. , dufour , e. , forestini , m. 2000 , a&a , 358 , 593 silva - villa , e. , sirianni , m. , zuluaga , j. 2008 , revmexaa , 44 , 57 sirianni , m. , nota , a. , de marchi , g. , leitherer , c. , clampin , m. 2000 , apj , 533 , 203 sirianni , m. , nota , a. , de marchi , g. , leitherer , c. , clampin , m. 2002 , apj , 579 , 275 slesnick , c. l. , hillenbrand , l. a. , massey , p. 2002 , apj , 576 , 880 slesnick , c. l. , hillenbrand , l. a. , carpenter j. m. 2004 , apj , 610 , 1045 song , i. , zuckerman , b. , bessel , m. s. 2004 , apj , 600 , 1016 stelzer , b. , preibisch , t. , alexander , f. et al . 2012 , a&a , 537 , 135 stolte , a. , brandner , w. , brandl , b. , zinnecker , h. 2006 , aj , 132 , 253 sung , h. , bessell , m. s. , chun , m .- y . 2004 , apj , 128 , 1684 sung , h. , bessell , m. s. , chun , m .- y . , karimov , r. , ibrahimov , m. 2008 , aj , 135 , 441 sung , h. , bessell , m. s. 2010 , aj , 140 , 2070 tripathi , a. , pandey , u. s. , kumar , b. 2014 , newa , 29 , 1 walker , m f. 1961 , apj , 133 , 438 wang , w. , boudreault , s. , goldman , b. , henning , th . , caballero , j. a. , bailer - jones , c. a. l. 2011 , a&a , 531 , 164 weidner , c. , kroupa , p. 2004 , apj , 348 , 187 weisz , d. r. , fouesneau , m. , hogg , d. w. , rix , h .- w . , dolphin , a. et al . 2013 , apj , 762 , 123 wilking , b. a. , gagn , m. , allen , l. e. 2008 , in star formation in the @xmath0 ophiuchi molecular cloud , ed . b. reipurth , 351 williams , d. m. , comeron , f. , rieke , g. h. , rieke , m. j. 1995 , apj , 454 , 144 in this appendix , we derive the value of the break point @xmath109 and normalisation @xmath33 in the composite lognormal+power law imf when the other parameters , @xmath107 , @xmath106 , and @xmath108 are given . the value of @xmath109 is given by the equality : @xmath238 after a few developments , one can show that this leads to a quadratic equation in @xmath239 : @xmath240 the discriminant of eq . [ eqa2 ] is given by : @xmath241 in the mcmc chain , we retain steps that satisfy @xmath242 . for each step at which this condition is satisfied , eq . [ eqa2 ] has two solutions which are given by : @xmath243 and , @xmath244 we further require that @xmath245 and in the mcmc chain we assign to @xmath109 the value of @xmath246 that satisfies this condition . we find that for all parameters that satisfy @xmath247 , @xmath248 . with knowledge of @xmath109 , @xmath108 , @xmath106 , and @xmath107 , it is straightforward to derive the normalisation term @xmath249 for each permutation of these parameters in the monte carlo chain using the total mass of the cluster . in this appendix , we derive the values of the non - independent parameters in the three - component power law mass function , when the values of the independent variables @xmath110 , @xmath111 , and @xmath112 , and @xmath40 vary in the monte carlo chain . for each set of values of [ @xmath110,@xmath111,@xmath112 , m@xmath250 , the values of @xmath40 , and @xmath251 can be derived using the following set of equations : where @xmath254 , @xmath255 , @xmath256 , @xmath158 is the number of stars in the cluster , @xmath257 is the mass of the cluster , and @xmath172 and @xmath236 are the minimum and maximum masses of stars present in the cluster , respectively . developing these integrals and replacing @xmath258 by @xmath259 yields to the following set of equations : @xmath260 \right . & \nonumber \\ + \frac{1}{m_{k1}^{-\gamma_{k2}-1 } } \frac{1}{\gamma_{k2 } } \left[m_{k1}^{-\gamma_{k2}}-m_{k2}^{-\gamma_{k2}}\right ] & \nonumber \\ + \frac{1}{m_{k2}^{-\gamma_{k3}-1 } } \frac{1}{\gamma_{k3 } } \left[m_{k2}^{-\gamma_{k3}}-m_{max}^{-\gamma_{k3}}\right ] & \left . \left(\frac{m_{k2}}{m_{k1}}\right)^{-\gamma_{k2}-1 } \right\ } \nonumber \\ -n_{*}=0 & \label{eqb3}\end{aligned}\ ] ] @xmath261 \right . & \nonumber \\ + \frac{1}{m_{k1}^{-\gamma_{k2}-1 } } \frac{1}{1-\gamma_{k2 } } \left[m_{k2}^{1-\gamma_{k2}}-m_{k1}^{1-\gamma_{k2 } } \right ] & \nonumber \\ + \frac{1 } { m_{k2}^{-\gamma_{k3}-1 } } \frac{1}{1-\gamma_{k3 } } \left[m_{max}^{1-\gamma_{k3}}-m_{k2}^{1-\gamma_{k3 } } \right]&\left.\left ( \frac{m_{k2}}{m_{k1}}\right)^{-\gamma_{k2}-1}\right\ } \nonumber \\ -m_{cl}= 0 , & \label{eqb4}\end{aligned}\ ] ] with @xmath110 , @xmath111 , @xmath112 , @xmath113 known at each step in the chain and with @xmath172 , @xmath236 , @xmath257 , and @xmath158 constant for each cluster , we solve eqs . [ eqb3 ] and [ eqb4 ] using a modified version of powell algorithm for functions minimisation ( powell 1964 ; press et al . 2007 ) and derive the values of @xmath40 and @xmath251 .
the universality of the stellar initial mass function ( imf ) is tested using bayesian statistics with a sample of eight young galactic stellar clusters ( ic 348 , onc , ngc 2024 , ngc 6611 , ngc 2264 , @xmath0 ophiuchi , chameleon i , and taurus ) . we infer the posterior probability distribution function ( ppdf ) of the imf parameters when the likelihood function is described by a tapered power law function , a lognormal distribution at low masses coupled to a power law at higher masses , and a multi - component power law function . the inter - cluster comparison of the ppdfs of the imf parameters for each likelihood function shows that these distributions do not overlap within the @xmath1 uncertainty level . furthermore , the most probable values of the imf parameters for most of the clusters deviate substantially from their values for the galactic field stellar imf . we also quantify the effects of taking into account the completeness correction as well as the uncertainties on the measured masses . the inclusion of the former affects the inferred ppdfs of the slope of the imf at the low mass end while considering the latter affects the ppdfs of the slope of the imf in the intermediate- to high mass regime . as variations are observed in all of the imf parameters at once and for each of the considered likelihood functions , even for completeness corrected samples , we argue that the observed variations are real and significant , at least for the sample of eight clusters considered in this work . the results presented here clearly show that the imf is not universal . [ firstpage ] galaxies : star clusters - turbulence - ism : clouds - open clusters and associations