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A new startup called Oak Labs is bringing smart dressing rooms to Ralph Lauren and the broader retailer landscape ahead of the holidays. To compare Oak Labs mirror to character Cher Horowitz’s computerized closet in the movie Clueless is a disservice. The mirrors are far more technologically advanced than Cher’s old white IBM. When a customer walks into one of Ralph Lauren’s smart dressing rooms, the lighting immediately brightens and the items they’ve picked out from the store appear on the mirror. Oak Lab’s smart mirror recognizes and accounts for any clothing a customer brings into the room and allows them to ping a sales representative if they need something in another size or want to try a different article of clothing altogether. The mirrors also come equipped with five language options and allow users to change the lighting in the room to one of three schemes. The technology is very similar to a project cofounder Healey Cypher was working on a year ago at eBay. Oak Labs was cofounded earlier this year by a former head of retail innovation at eBay enterprise group, Healey Cypher, along with Michael Franklin, Flynn Joffray, and former head of design at eBay retail innovation, Darren Endo. While at eBay, Cypher worked on developing interactive mirrors that do many of the same tasks that Oak Lab’s mirrors do, like recognizing clothing using radio frequency identification tags. But eBay’s mirrors also included a checkout option, allowing users to make purchases directly from their dressing room using PayPal. The company launched the new technology at the Rebecca Minkoff store in Soho last November. EBay’s retail innovation unit was in flux after a key investor pressured it to reorganize. As part of the change-up, it was decided that eBay enterprise would be sold or spun off. At that point, Cypher decided to quit eBay and go into business for himself. Since its founding in May, the company has raised $4.1 million in funding, led by Wing Venture Capital. In the last 15 years, a handful of retailers have played around with putting touch screens in their dressing rooms. Prada, most notably, spent millions of dollars making its stores “smarter” in the early 2000s. More recently, Macy’s added smart dressing rooms to five of its stores. Retailers believe that if they can quickly get customers into the fitting room with the right clothing, in the right size, those shoppers are more likely to make a purchase. Smart dressing rooms help cut down on the inefficiency of hailing a sales rep and sending them out onto the floor to search for an item. No retailer has yet been able to really nail this experience or make it cost-effective, and Oak Labs certainly has its work cut out for it. To make the business work, it will need to hit a large number of retailers and likely expand into other products. In the meantime, you can go to Ralph Lauren’s 5th Avenue store in New York to get a little taste of the future. *Update: This article has been corrected to reflect the correct spelling of Oak Labs cofounder Healey Cypher. An earlier version referred to him as Healey Cipher. ||||| Marina Nazario/Business Insider Ralph Lauren launched interactive mirrors in its New York City flagship store on Wednesday. You can now change the lighting in the fitting room, request a different size, browse through other items in the store, or interact with a sale associate through the mirror. I went to Ralph Lauren to check it out and my shopping experience will never be the same. ||||| EBay and fashion label Rebecca Minkoff have brought to life the enviable computerized closet from Clueless — only this time you can make over your closet from your phone. This morning, eBay debuted a new type of dressing room at the designer’s Greene Street store in New York’s Soho. The dressing room features a computerized mirror display, which in itself is pretty cool. But what may prove more interesting is how eBay is using the display to push mobile payment platform PayPal. Minkoff’s smart dressing room works well. In a demo, the smart room was able to recognize the shirt I brought in, recommend clothes to pair with it, and send instructions to a sales clerk — if I needed another size or color, for example. At the end of my session, the mirror gave me the option to check out right from my stall. The only form of mobile payment the smart dressing room accepts is PayPal. Those who have the PayPal app on their phone can check in when they enter the store, so when they’re ready to pay, they just hit a button on the mirror display. Then a salesperson comes to the door, offers to pack up the goods, and sends the customer on her way. For those without PayPal, sales clerks have a tablet point of sale enabled with a credit card reader. I didn’t get a chance to make a purchase with PayPal’s app, so I can’t say whether it is as seamless as eBay’s PR team says it is (I only attended a demo, and the store won’t be payment-ready until Saturday when it officially opens). However, if it does provide that kind of frictionless payment experience for customers, it could help PayPal better access the physical retail market — a market ten times the size of the e-commerce space, according to Healey Cypher, head of retail innovation at eBay. That’s a big opportunity, but not an easy one to tackle. Smart dressing rooms are not new, but they are difficult to get right. Prada spent millions digitizing its stores in the early 2000s, and Macy’s recently announced the rollout of smart dressing rooms in five of its stores. For Macy’s, the smart dressing room experience is as much about getting consumers the products that they need quickly as it is about making the check-out process frictionless. For that, Macy’s has linked up with Apple Pay. Apple Pay is a scary prospect for PayPal, which, though its desktop and mobile payments platform has been around for far longer, doesn’t have nearly the user base that Apple’s iTunes has. Still, that doesn’t mean that PayPal is dead in the water. There’s real potential for mobile payment adoption in retail, especially in apparel. Cypher says that when consumers try clothes on in fitting rooms, 70 percent of the time that leads to a sale, “So what we’re trying to do is get people in the fitting room,” says Cypher. The time to tap into that market is now. Mobile payments may be fast catching on. Not even a month into the release of Apple Pay, nearly one percent of transactions at Whole Foods are made with Apple’s new platform. PayPal will need to move fast to make its mobile payments system equally relevant. EBay and PayPal are soon to be separate companies, so it’s possible that eBay’s smart dressing mirror will branch out to accept other forms of mobile payment. For the moment, however, PayPal is the only mobile payment system Rebecca Minkoff will be accepting, and that may hold true for the other companies using eBay’s smart display. At the very least, eBay is looking to expand the use of its innovative display. Rob Veres, senior director of innovation at eBay, says the company is focusing on other partnerships for its digital display and will be rolling out new products in the coming months. Right now they’re working with Stanford Shopping Center on an updated digital directory that will not only guide customers to the stores they’re looking for, but push information about sales and discounts. Ultimately, he says, eBay will be looking to create a more personalized shopping experience with these directories. “It will recognize you as you approach and … recommend stores and sales,” says Veres. If eBay can really get consumers to interact with its digital displays, all the while pushing PayPal as its preferred method of payment, there’s hope that the mobile payment app will see some meaningful traction. Neither smart shopping nor mobile payments is an easy win, though, and the company has a lot of ground to cover in terms of user base. Still, these new digital displays are certainly an interesting play.

– This week, Ralph Lauren installed smart dressing rooms in its 5th Avenue store in New York—and VentureBeat says they're even more space-age than Cher Horowitz's Clueless closet. The dressing rooms, the brainchild of startup Oak Labs, feature touchscreen mirrors that, per Quartz, use radio-frequency identification (RFID) to identify and display the items being tried on. That way, customers can easily ping sales reps if they need new colors, new sizes, or new items entirely, and the reps get notifications on their iPads. The rooms also feature lighting that automatically brightens when the customer enters, and people can use the mirror to change the lighting to one of three different schemes ("Fifth Avenue Daylight," "East Hampton Sunset," or "Evening at the Polo Bar"). The mirrors have five language options. Marina Nazario tried one of the dressing rooms, and she writes at Business Insider that "it blew my mind." She notes that the mirrors easily allow customers to browse through other items at the store—and even offer suggestions of items you might like. And they allow you to interact with a sales rep for more than just grabbing a new size—select "I just need some help!" if you simply crave human interaction. You can also have the mirror send you information about items you like if you won't be purchasing them that day. "My shopping experience will never be the same," she writes. VentureBeat notes that Prada and Macy's also have some "smart" dressing rooms, but no store has yet been able to make the experience truly cost-effective. Similar mirrors launched at the Rebecca Minkoff store in New York last year allow customers to make purchases using PayPal. (A uniform supplier figured out how much time women spend deciding what to wear.)

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Wildlife Refuge System Operations Enhancement Act of 2007''. SEC. 2. FINDINGS AND PURPOSE. (a) Findings.--The Congress finds the following: (1) The National Wildlife Refuge System is a unique network of Federal lands that provides wildlife dependent recreational opportunities to the overwhelming majority of the 40 million people who visit at least one refuge in a year. (2) There are 547 national wildlife refuges comprised of 96 million acres of Federal land. These refuges are located in every State, island possession, and territory of the United States. These lands are a national treasure. (3) A decade ago, the Congress enacted the National Wildlife Refuge System Improvement Act of 1997 (Public Law 105- 97), which was a landmark law that established for the first time an organic statute and mission statement for the System. (4) Four years ago, the National Wildlife Refuge System celebrated the 100th anniversary of the designation of the first refuge by President Theodore Roosevelt at Pelican Island, Florida on March 14, 1903. (5) In commemoration of that historic event, the Congress created the National Wildlife Refuge System Centennial Commission and appropriated the highest level of funding ever for refuge operations. (6) Since the end of that anniversary celebration, however, funding for refuge operations has significantly declined, and the United States Fish and Wildlife Service has not received adequate funding to offset either inflation or uncontrollable fixed costs like salary and benefit increases, energy costs, and General Services Administration rent adjustments. (7) The net result is that the United States Fish and Wildlife Service now has 600 vacant positions with a total workforce of only 9,000 full-time employees. There are also now 86 refuges that are closed to the public and 188 refuges that are unstaffed. (8) According to the Cooperative Alliance for Refuge Enhancement, a coalition of 20 conservation and hunting organizations including Ducks Unlimited, the National Audubon Society, and the Congressional Sportsmen's Foundation, ``[t]he National Wildlife Refuge System faces a crippling conservation deficit''. (9) According to the United States Fish and Wildlife Service with respect to the Northeast Region of the Service, ``[i]n three years, 74 percent of the national wildlife refuges (70 refuges) would be operating either `in the red' or at crisis levels, in 5 years, 89 percent, and in 7 years, 93 percent''. This funding crisis is being felt throughout the National Wildlife Refuge System. (10) It is essential that the Congress appropriate additional funds for refuge operations and enact new funding mechanisms that alleviate some, if not all, of these staggering operational deficits. (b) Purpose.--The purpose of this Act is to establish new funding mechanisms to pay for the otherwise unfunded costs of operating and maintaining the National Wildlife Refuge System. TITLE I--MIGRATORY BIRD HUNTING STAMPS SEC. 101. PRICE OF STAMP. (a) Increase in Price.-- (1) In general.--Sections 2(b) of the Act of March 16, 1934 (chapter 71; 16 U.S.C. 718b(b)), popularly known as the Duck Stamp Act, is amended to read as follows: ``(b) Price of Stamp.--A person authorized to sell stamps under this section shall collect, for each stamp sold-- ``(1) $20 for a stamp for any of hunting years 2008 through 2010; and ``(2) $25 for a stamp for each hunting year after hunting year 2010.''. (2) Limitation on application.--This subsection shall not affect the application of section 2 of such Act before July 1, 2008. (b) Use of Additional Funds.--Section 4(b) of such Act (16 U.S.C. 718d(b)) is amended-- (1) in paragraph (1), by striking ``So much'' and inserting ``Subject to paragraph (3), so much''; (2) in paragraph (2), by striking ``paragraph (3) and subsection (c)'' and inserting ``paragraphs (3) and (4)''; and (3) by adding at the end the following: ``(4) Refuge operations.--The amount received for each stamp sold in excess of $15.00 shall be used by the Secretary for the costs of national wildlife refuge operations.''. SEC. 102. SENSE OF CONGRESS. It is the sense of the Congress that nothing in this title should directly or indirectly cause a net decrease in total funds received by the United States Fish and Wildlife Service for national wildlife refuge operations account below the level that would otherwise have been received but for the enactment of this section. TITLE II--SPECIAL POSTAGE STAMP SEC. 201. SHORT TITLE. This title may be cited as the ``National Wildlife Refuge System Semipostal Stamp Act of 2007''. SEC. 202. SPECIAL POSTAGE STAMP FOR THE NATIONAL WILDLIFE REFUGE SYSTEM. (a) In General.--In order to afford a convenient way for members of the public to contribute to funding for the operations of the National Wildlife Refuge System, the United States Postal Service shall provide for a special postage stamp in accordance with subsection (b). (b) Terms and Conditions.--The issuance and sale of the stamp referred to in subsection (a) shall be governed by section 416 of title 39, United States Code, and regulations under such section, subject to the following: (1) Disposition of proceeds.--All amounts becoming available from the sale of such stamp shall be transferred to the United States Fish and Wildlife Service, for the purpose described in subsection (a), through payments which shall be made at least twice a year. (2) Duration.--Such stamp shall be made available to the public for a period of at least 3 years, beginning no later than 12 months after the date of the enactment of this Act. (3) Limitation.--Such stamp shall not be counted for purposes of applying any numerical limitation under subsection (e)(1)(C) of such section. TITLE III--DESIGNATION OF INCOME TAX OVERPAYMENT SEC. 301. SHORT TITLE. This title may be cited as ``National Wildlife Refuge Checkoff Act of 2007''. SEC. 302. DESIGNATION OF OVERPAYMENTS AND CONTRIBUTIONS FOR THE NATIONAL WILDLIFE REFUGE SYSTEM TRUST FUND. (a) In General.--Subchapter A of chapter 61 of the Internal Revenue Code of 1986 (relating to returns and records) is amended by adding at the end thereof the following new part: ``PART IX--DESIGNATION OF OVERPAYMENTS AND CONTRIBUTIONS FOR THE NATIONAL WILDLIFE REFUGE SYSTEM TRUST FUND ``Sec. 6097. Amounts for National Wildlife Refuge System Trust Fund. ``SEC. 6097. AMOUNTS FOR NATIONAL WILDLIFE REFUGE SYSTEM TRUST FUND. ``(a) In General.--With respect to each taxpayer's return for the taxable year of the tax imposed by chapter 1, such taxpayer may designate that-- ``(1) $1 of any overpayment of such tax for such taxable year, and ``(2) any cash contribution which the taxpayer includes with such return, be paid over to the National Wildlife Refuge System Trust Fund. ``(b) Joint Returns.--In the case of a joint return showing an overpayment of $2 or more, each spouse may designate $1 of such overpayment under subsection (a)(1). ``(c) Manner and Time of Designation.--A designation under subsection (a) may be made with respect to any taxable year only at the time of filing the return of the tax imposed by chapter 1 for such taxable year. Such designation shall be made on the first page of the return. ``(d) Overpayments Treated as Refunded.--For purposes of this title, any overpayment of tax designated under subsection (a) shall be treated as being refunded to the taxpayer as of the last date prescribed for filing the return of tax imposed by chapter 1 (determined without regard to extensions) or, if later, the date the return is filed.''. (b) Clerical Amendment.--The table of parts for subchapter A of chapter 61 of such Code is amended by adding at the end thereof the following new item: ``Part IX. Designation of Overpayments and Contributions for the National Wildlife Refuge System Trust Fund.''. (c) Effective Date.--The amendments made by this section shall apply to taxable years ending after the date of enactment of this Act. SEC. 303. ESTABLISHMENT OF NATIONAL WILDLIFE REFUGE SYSTEM TRUST FUND. (a) In General.--Subchapter A of chapter 98 of the Internal Revenue Code of 1986 (relating to trust fund code) is amended by adding at the end thereof the following new section: ``SEC. 9511. NATIONAL WILDLIFE REFUGE SYSTEM TRUST FUND. ``(a) Creation of Trust Fund.--There is established in the Treasury of the United States a trust fund to be known as the `National Wildlife Refuge System Trust Fund', consisting of such amounts as may be appropriated or credited to the National Wildlife Refuge System Trust Fund as provided in this section or section 9602(b). ``(b) Transfer to National Wildlife Refuge System Trust Fund of Amounts Designated.--There is hereby appropriated to the National Wildlife Refuge System Trust Fund amounts equivalent to the amounts designated under section 6097 and received in the Treasury. ``(c) Expenditures From Trust Fund.-- ``(1) In general.--The Secretary shall pay, not less often than quarterly, to the United States Fish and Wildlife Service from the National Wildlife Refuge System Trust Fund an amount equal to the amount in such Fund as of the time of such payment less any administrative expenses of the Secretary which may be paid under paragraph (2). ``(2) Administrative expenses.--Amounts in the National Wildlife Refuge System Trust Fund shall be available to pay the administrative expenses of the Department of the Treasury directly allocable to-- ``(A) modifying the individual income tax return forms to carry out section 6097, ``(B) carrying out this chapter with respect to such Fund, and ``(C) processing amounts received under section 6097 and transferring such amounts to such Fund.''. (b) Clerical Amendment.--The table of sections for such subchapter A is amended by adding at the end thereof the following new item: ``Sec. 9511. National Wildlife Refuge System Trust Fund.''.

National Wildlife Refuge System Operations Enhancement Act of 2007 - Increases the price of Migratory Bird Hunting and Conservation Stamps. Requires amounts received for such stamps sold in excess of $15.00 to be used by the Secretary of the Interior for the costs of national wildlife refuge operations. National Wildlife Refuge System Semipostal Stamp Act of 2007 - Sets forth provisions for the issuance and sale of a special postage stamp in order to afford a convenient way for the public to contribute toward funding the operations of the National Wildlife Refuge System. National Wildlife Refuge Checkoff Act of 2007 - Permits a taxpayer to designate that $1 of any tax overpayment, and any cash contribution which the taxpayer includes with such return, shall be deposited into the National Wildlife Refuge System Trust Fund established by this Act. Requires the Secretary of the Treasury to make payments to the U.S. Fish and Wildlife Service (USFWS) from such Fund.

soient @xmath0 un corps de caractristique zro , @xmath5 une clture algbrique de @xmath0 , et @xmath6 . toute @xmath0-varit algbrique gomtriquement intgre @xmath7 , de corps des fonctions @xmath8 , on associe dune part son groupe de brauer cohomologique @xmath9 , dautre part le groupe de brauer non ramifi @xmath10 quon notera ici simplement @xmath11 . pour la dfinition et les proprits de base de ces groupes , on renvoie @xcite , @xcite et @xcite . rappelons simplement que si @xmath7 est lisse sur @xmath0 , alors la restriction au point gnrique induit une inclusion @xmath12 et que si @xmath7 est projective et lisse , alors cette inclusion induit un isomorphisme @xmath13 soit @xmath14 un entier , @xmath15 et @xmath1 un groupe fini vu comme @xmath0-groupe constant , et @xmath16 un @xmath0-plongement . lespace homogne quotient @xmath18 . le corps des fonctions @xmath19 de @xmath17 est le corps @xmath20 des invariants du corps des fonctions @xmath21 sous laction de @xmath1 . ces notations seront conserves dans tout larticle . on se propose dexaminer le groupe de brauer non ramifi @xmath22 . ce groupe ( isomorphisme non unique prs ) ne dpend que de @xmath1 , il ne dpend ni de @xmath23 ni du plongement @xmath24 . comme @xmath17 est une @xmath0-varit lisse intgre , on a @xmath25 . on va suivre ici la mthode purement algbrique quavait utilise bogomolov ( @xcite , ( * ? ? ? 7.1 ) ) lorsque @xmath0 est algbriquement clos . ceci permet dtendre certains des rsultats tablis par des mthodes arithmtiques par harari @xcite et par demarche @xcite sur le sous - groupe @xmath26,\ ] ] sous - groupe form des classes qui sannulent par passage au corps des fonctions @xmath27 de @xmath28 . en particulier , on montre ici ( corollaire [ racines ] ) que pour tout corps @xmath0 de caractristique zro ne possdant quun nombre fini de racines de lunit , pour @xmath29 avec @xmath1 fini constant dordre premier au cardinal du groupe des racines de lunit dans @xmath0 , on a @xmath30 . etant donn un corps @xmath0 de caractristique zro , pour tout premier @xmath31 impair et tout entier @xmath32 , lextension @xmath33 est cyclique . il en est encore ainsi pour @xmath34 si @xmath35 est un carr dans @xmath0 . on note @xmath36 la condition : _ pour tout sous - groupe cyclique @xmath37 , lextension @xmath38 est cyclique . _ pour @xmath39 un groupe ablien , @xmath40 un entier et @xmath41 un nombre premier , on note @xmath42 \subset a$ ] le sous - groupe annul par @xmath23 et on note @xmath43 le sous - groupe de torsion @xmath41-primaire . on note @xmath44 le groupe de brauer normalis , cest - - dire le groupe des lments qui sannulent en limage du point @xmath45 . on a des inclusions naturelles compatibles @xmath53 et @xmath54 , et cette dernire flche est un isomorphisme car @xmath55 est une varit @xmath0-rationnelle . ceci tablit ( i ) et ( ii ) . lnonc de finitude ( iii ) vaut plus gnralement pour les corps de fonctions de varits projectives , lisses , gomtriquement connexes qui sont gomtriquement unirationnelles . rappelons brivement la dmonstration . pour toute @xmath0-varit projective , lisse , gomtriquement intgre @xmath55 , notant @xmath56 , on a une suite exacte @xmath57 \to h^1(\frak{g},{\operatorname{pic}}(\ov{x})).\ ] ] si @xmath55 est gomtriquement unirationnelle , alors le module galoisien @xmath58 est un groupe ablien libre de type fini , et le groupe @xmath59 est fini . ceci suffit conclure . [ fischer ] supposons le groupe @xmath1 ablien et la condition @xmath36 satisfaite . il existe une @xmath0-varit @xmath61 telle que le produit @xmath62 est @xmath0-birationnel un espace projectif sur @xmath0 . on dit que deux @xmath0-varits @xmath63 et @xmath64 sont stablement @xmath0-birationnellement quivalentes sil existe des espaces projectifs @xmath65 et @xmath66 tels que @xmath67 est @xmath0-birationnel @xmath68 . daprs une version du lemme sans nom , pour un groupe fini @xmath1 , des @xmath0-groupes spciaux @xmath69 et @xmath70 et des plongements @xmath71 et @xmath72 , le quotient @xmath73 est stablement @xmath0-birationnel @xmath74 ( ( * ? ? ? les produits de groupes @xmath75 ( @xmath23 variable ) sont spciaux . si donc lon a un plongement @xmath76 , un plongement @xmath77 et un plongement @xmath78 , o chacun des groupes @xmath55 et @xmath79 est un groupe spcial linaire , alors @xmath18 est stablement @xmath0-birationnel @xmath80 . pour tablir la proposition , on est donc ramen au cas o @xmath81 est un groupe ablien cyclique @xmath31-primaire , pour @xmath31 un nombre premier . lextension @xmath82 est cyclique si @xmath31 est impair , et cest encore le cas si @xmath34 daprs lhypothse de la proposition . suivant voskresenski , rappelons comment cela se traduit en termes de tores . soit @xmath83 et soit @xmath84 . le groupe ablien libre de base les lments de @xmath85 , qui est un @xmath86-module de permutation , senvoie de faon vidente et @xmath86-quivariante sur le groupe @xmath85 . on note @xmath87 le noyau de cette application . on a donc la suite exacte de @xmath86-modules continus discrets : @xmath88 par dualit , on obtient une suite exacte de @xmath0-groupes algbriques de type multiplicatif @xmath89 o @xmath81 , @xmath90 est un @xmath0-tore et @xmath91 est un @xmath0-tore quasi - trivial , en particulier un @xmath0-groupe spcial . ainsi ( ( * ? ? ? 4.9 ) ) , pour tout @xmath0-plongement @xmath92 , le quotient @xmath18 est stablement @xmath0-birationnel au @xmath0-tore @xmath90 . le @xmath0-tore @xmath90 est dploy par une extension cyclique . rappelons comment ceci implique quil existe un @xmath0-tore @xmath93 tel que @xmath94 est @xmath0-birationnel un espace projectif , ce qui achvera la dmonstration . on sait ( voskresenski , endo - miyata ) que tout @xmath0-tore @xmath90 dploy par une extension galoisienne @xmath95 admet une rsolution flasque , cest - - dire quil existe une suite de @xmath0-tores dploys par lextension @xmath95 @xmath96 o @xmath91 est un @xmath0-tore quasi - trivial , donc @xmath0-birationnel un espace projectif et @xmath97 est un @xmath0-tore flasque ( voir ( * ? ? ? * lemme 3 p. 18 ) et @xcite ) . supposons @xmath95 cyclique . daprs un thorme de endo et miyata ( voir ( * ? ? ? * prop . 2 , p. 184 ) ) tout @xmath0-tore flasque @xmath98 dploy par une telle extension est un facteur direct dun @xmath0-tore quasitrivial : il existe un @xmath0-tore @xmath99 tel que le @xmath0-tore @xmath100 soit @xmath0-isomorphe un @xmath0-tore quasitrivial . le thorme 90 de hilbert et la rsolution flasque ci - dessus assurent alors que la @xmath0-varit @xmath0-rationnelle @xmath91 est @xmath0-birationnelle au produit @xmath101 . * notation * soit @xmath1 un groupe fini . pour tout @xmath1-module @xmath113 et tout entier @xmath114 , on dfinit les sous - groupes @xmath115 comme les sous - groupes forms des lments de @xmath116 do nt la restriction chaque sous - groupe cyclique , resp . bicyclique , resp . ablien @xmath117 est nulle . par dfinition , un groupe bicyclique est un groupe ablien engendr par deux lments . un @xmath1-module de permutation est un groupe ablien libre qui admet une base respecte par laction de @xmath1 . cest une somme directe de @xmath1-modules @xmath118 $ ] pour divers sous - groupes @xmath117 . on a @xmath119 , et @xmath120 car tout caractre de @xmath1 nul sur tout lment de @xmath1 est nul . en utilisant le lemme de shapiro , on tend ces rsultats sur le @xmath1-module @xmath121 aux @xmath1-modules de permutation . ceci permet dtablir le : \(vi ) soit @xmath126 une suite exacte de @xmath1-modules . si @xmath127 est un @xmath1-module sans torsion avec action triviale de @xmath1 , cette suite induit des isomorphismes @xmath128 , @xmath129 , @xmath130 . @xmath107 toute fonction inversible sur @xmath15 est constante , et le groupe de picard de @xmath75 est nul . la flche diviseur @xmath139 sur le corps des fonctions de @xmath55 donne donc naissance une suite exacte de @xmath1-modules @xmath140 le @xmath1-module @xmath141 est le groupe ablien libre sur les points de codimension 1 de @xmath55 . cest donc un @xmath1-module de permutation . pour tout corps @xmath0 on a la suite exacte de @xmath1-modules ( avec action triviale ) @xmath144 o @xmath145 est sans torsion . daprs le lemme [ lemmesha ] ( vi ) , on a @xmath146 lnonc ( b ) rsulte alors de lnonc ( a ) . pour la torsion impaire , ou sous lhypothse @xmath36 , cet argument donne une autre dmonstration de la finitude de @xmath147 ( lemme [ lemmeinitial ] ) . il suffit dobserver que le groupe @xmath148 , et donc aussi @xmath149 , est fini . soit @xmath41 premier divisant lordre de @xmath1 . le groupe @xmath150 est soit fini soit isomorphe @xmath151 . dans les deux cas , le groupe @xmath152 est fini . cest clair dans le premier cas . dans le second , @xmath153 . dans le cas ( a ) , on a @xmath160 , car ce groupe est annul par lordre de @xmath1 et par lordre de @xmath131 . le thorme [ theoprincip2 ] donne alors ( a ) , et ( b ) est alors une consquence immdiate , puisque @xmath161 . sur @xmath162 , la condition @xmath163 est trivialement satisfaite , et @xmath164 . ceci donne ( c1 ) , et les noncs ( c2 ) et ( c3 ) sen suivent . comme me la indiqu c. demarche , les @xmath31-groupes quil tudie dans @xcite fournissent , pour @xmath34 , un exemple de groupe fini @xmath1 dordre 64 tel que le groupe de brauer non ramifi normalis @xmath166 possde un lment algbrique qui ne sannule pas dans @xmath167 . lhypothse faite sur les racines de lunit implique aussi que pour tout anneau de valuation discrte de rang 1 de @xmath20 , contenant @xmath0 , laction des sous - groupes de dcomposition de @xmath1 sur linertie est triviale . on peut donc copier largument de bogomolov ( cf . 6.1 , thm . 7.1 ) ) , qui mne linclusion @xmath173 dans @xmath174 , on a donc les galits @xmath175 \(i ) soit @xmath181 tel que @xmath182 . le groupe de brauer non ramifi algbrique normalis @xmath183= ker[h^2_{nr}(g , k(x)^{\times } ) \to h^2(g,\k(x)^{\times})]\ ] ] sidentifie un sous - groupe de @xmath184,$ ] o @xmath39 parcourt les sous - groupes abliens de @xmath1 . le flches @xmath189 et @xmath190 sont compatibles , comme on le vrifie immdiatement . lnonc ( i ) rsulte alors de la suite exacte de @xmath1-modules action triviale @xmath191 dfinie par la multiplication par @xmath192 sur @xmath193 . le thorme [ racinesfinies ] sapplique aux corps de nombres et plus gnralement aux corps de type fini sur un corps de nombres , mais aussi aux corps @xmath31-adiques et aussi aux rels . sur de tels corps , on voit donc que si le groupe @xmath1 na pas de caractres , le groupe de brauer non ramifi algbrique normalis est nul . sur un corps de nombres , ceci avait t tabli par harari ( * ? ? ? 4 ) , qui donne une formule pour le groupe de brauer non ramifi algbrique normalis comme sous - groupe de @xmath196 , formule qui implique clairement que ce groupe est nul si @xmath1 na pas de caractres . soit @xmath156 . le groupe de brauer non ramifi algbrique normalis de @xmath197 @xmath198\ ] ] sidentifie un sous - groupe de @xmath199,$ ] o @xmath39 parcourt les sous - groupes abliens de @xmath1 . @xmath107 j .- l . colliot - thlne , birational invariants , purity and the gersten conjecture , in _ k - theory and algebraic geometry : connections with quadratic forms and division algebras _ , ams summer research institute , santa barbara 1992 , ed . w. jacob and a. rosenberg , proceedings of symposia in pure mathematics * 58 * , part i ( 1995 ) p. 164 . colliot - thlne et j .- j . sansuc , the rationality problem for fields of invariants under linear algebraic groups ( with special regards to the rationality problem ) , in _ proceedings of the international colloquium on algebraic groups and homogeneous spaces _ ( mumbai 2004 ) , ed . v. mehta , tifr mumbai , narosa publishing house ( 2007 ) , 113186 . kunyavski , the bogomolov multiplier of finite simple groups , in _ cohomological and geometric approaches to rationality problems _ , 209217 , progr . math . * 282 * , birkh " auser boston , inc . , boston , ma , 2010 .

soit @xmath0 un corps , @xmath1 un groupe fini , @xmath2 un plongement . pour @xmath0 alg ' ebriquement clos , bogomolov a donn ' e une formule pour le groupe de brauer non ramifi du quotient @xmath3 . on examine ce que donne sa mthode sur un corps @xmath0 quelconque ( de caractristique nulle ) . par cette mthode purement algbrique , on retrouve et tend des rsultats obtenus par harari et par demarche au moyen de m ' ethodes arithmtiques , comme la trivialit du groupe de brauer non ramifi pour @xmath4 et @xmath1 dordre impair . let @xmath0 be a field , @xmath1 a finite group , @xmath2 an embedding . for @xmath0 an algebraically closed field , bogomolov gave a formula for the unramified brauer group of the quotient @xmath3 . we develop his method over any characteristic zero field . this purely algebraic method enables us to recover and generalize results of harari and of demarche over number fields , such as the triviality of the unramified brauer group for @xmath4 and @xmath1 of odd order .

the recent proliferation of networks operating on unlicensed bands , most notably 802.11 and bluetooth , has stimulated research into the study of how different systems competing for the same spectrum interact . communication on unlicensed spectrum is desirable essentially because it is free , but users are subject to random interference generated by the transmissions of other users . most research to date has assumed devices have no natural incentive to cooperate with one another . for instance , a wireless router in one apartment is not concerned about the interference it generates in a neighboring apartment . following from this assumption , various game - theoretic formulations have been used to model the interplay between neighboring systems @xcite , @xcite , @xcite , @xcite , @xcite . an important conclusion stemming from this body of work is that for single - stage games the nash equilibria ( n.e . ) are typically unfavorable , resulting in inefficient allocations of resources to users . a quintessential example is the following . consider a system where a pair of competing links is subjected to white - noise and all cross - gains are frequency - flat . suppose the transmitters wish to select a one - time power allocation across frequency subject to a constraint on the total power expended ( this problem is studied in @xcite , @xcite , @xcite where it is referred to as the _ gaussian interference game _ ) . it is straightforward to reason ( via a waterfilling argument ) that the selection by both users of frequency - flat power allocations , each occupying the entire band , constitutes a n.e .. this _ full spread _ power allocation can be extremely inefficient . consider a symmetric system where the cross - gains and direct - gains are equal . at high @xmath2 each link achieves a throughput of only 1 b / s / hz , instead of @xmath3 b / s / hz , which would be obtained if the links cooperated by occupying orthogonal halves of the spectrum . at an @xmath2 of 30 db , the throughput ratio between cooperative behavior and this full spread n.e . behavior , referred to as the _ price of anarchy _ , is about 5 . this example highlights an important point in relation to single - stage games between competing wireless links : users typically have an incentive to occupy all of the available resources . in this work a different approach is taken . rather than assuming total anarchy , that is , competition between _ all _ wireless links , we instead assume competition only between wireless links belonging to _ different networks_. wireless links belonging to the same network are assumed to _ cooperate_. in short , we assume competition on the network level , not on the link level . in a practical setting this may represent the fact that neighboring wireless systems are produced by the same manufacturer , or are administered by the same network operator . alternatively one may view the competition as being between coalitions of users @xcite . to make the problem analytically tractable but still retain its underlying mechanics , we assume each network operates under a random - access protocol , where users from a given network access the channel independently but with the same probability . analysis of random access protocols provides intuition for the behavior of systems operating under more complex protocols , as the access probability can broadly be interpreted as the average degrees of freedom each user occupies . for the case of competition on the link level , game - theoretic research of random - access protocols such as aloha have been conducted in @xcite and @xcite . in our model each network has a different density of nodes and chooses its access probability to maximize average throughput per user . note this access protocol is essentially identical to one in which users select a random fraction of the spectrum on which to communicate . thus an access probability of one corresponds to a full spread power allocation . we first assume all links in the system have the same transmission range and afterwards show that the results are only trivially modified if each link is assumed to have an i.i.d . random transmission range . we characterize the n.e . of this system for a fixed - rate model , where all users transmit at the same data rate . we show that unlike the case of competing links , a n.e . always exists and is _ unique_. furthermore for a large range of typical parameter values , the n.e . is not full spread nodes in at least one network occupy only a fraction of the bandwidth . we also identify two modes , delineated by the pathloss exponent @xmath0 . for @xmath1 , the n.e . behavior is distinctly different than for @xmath4 and possesses pseudo - cooperative properties . following this we show that the picture for the variable - rate model , in which users individually tailor their transmission rates to match the instantaneous channel capacity , remains unchanged . before concluding we present simulation results for the behavior of the system when the networks employ a greedy algorithm to optimize their throughput , operating under both a random access protocol , and a carrier sensing protocol . in section ii we formulate the system model explicitly . in section iii.a we introduce the random access protocol and analyze its n.e . behavior in the fixed - rate model . in section iii.b we analyze the variable - rate model . in section iv we extend our results to cover the case of variable transmission ranges . section v presents simulation results and the carrier sensing protocol . section vi summarizes and suggests extensions . section vii contains proofs of the main theorems presented . consider two wireless networks consisting of @xmath5 and @xmath6 tx - rx pairs , respectively . without loss of generality we will assume @xmath7 . the transmitting nodes are uniformly distributed at random in an area of size @xmath8 . to avoid boundary effects suppose this area is the surface of a sphere . thus @xmath9 is the density of transmitters ( or receivers ) in network @xmath10 . for each transmitter , the corresponding receiver is initially assumed to be located at a fixed range of @xmath11 meters with uniform random bearing . time is slotted and all users are assumed to be time synchronized . both networks operate on the same band of ( presumably unlicensed ) spectrum and at each time slot a subset of tx - rx pairs are simultaneously scheduled in each network . when scheduled a tx - rx pair uses all of the spectrum . it is generally desirable to schedule neighboring tx - rx pairs in different time slots . this scheduling model is a form of tdm , but is more or less analogous to an fdm model where each tx - rx pair is allocated a subset of the spectrum ( typically overlapping in some way with other tx - rx pairs in the network ) . transmitting nodes are full buffer in that they always have data to send . transmissions are assumed to use gaussian codebooks and interference from other nodes is treated as noise . initially we analyse the model where all transmissions in network @xmath10 occur at a common rate of @xmath12 . we refer to @xmath13 as the _ target _ @xmath14 . thus a transmission in network @xmath10 is successful iff @xmath15 . later we explore the model where transmission rates are individually tailored to match the instantaneous capacities of the channels . the signal power attenuates according to a power law with _ pathloss exponent _ @xmath16 . we assume a high-@xmath2 or _ interference limited _ scenario where the thermal noise is insignificant relative to the received power of interfering nodes and thus refer to the @xmath17 as the @xmath17 . for a given realization of the node locations the time - averaged throughput achieved by the @xmath18th tx - rx pair in network @xmath10 is then @xmath19 per complex d.o.f . , where @xmath20 is the fraction of time the @xmath18th tx - rx pair is scheduled . the average ( represented by the bar above the @xmath21 ) is essentially taken over the distribution of the interference as at different times different subsets of transmitters are scheduled . as for @xmath16 the bulk of the interference is generated by the strongest interferer , to make the problem tractable , we compute the @xmath17 as the receive power of the desired signal divided by the receive power of the _ nearest _ interferers signal . we refer to this as the _ dominant interferer _ assumption . denote the range of the nearest interferer to the @xmath18th receiver at time @xmath22 by @xmath23 . then @xmath24 the metric of interest to each network is its expected time - averaged rate per user , @xmath25\ ] ] the subscript @xmath26 indicates this expectation is taken over the geographic distribution of the nodes . as the setup is statistically symmetric , this metric is equivalent to the expected _ sum rate _ of the system , divided by @xmath27 , in the limit @xmath28 . suppose each network uses the following random access protocol . at each time slot each link is scheduled i.i.d . with probability @xmath29 . the packet size is @xmath12 for all communications in network @xmath10 . the variables @xmath30 are optimized over . let us first compute the optimal access probability for the case of a single network operating in isolation on a licensed band , as a function of the node density and the transmission range . this problem has recently been studied independently in @xcite-@xcite with equivalent results derived . in @xcite similar results are derived for the case where the @xmath17 is computed based on all interferers , not just the nearest . let the r.v . @xmath31 denote the number of interfering transmitters within range @xmath32 of the @xmath18th receiver . @xmath33 \\ & = p_i\sum_{k=1}^{n\lambda_i-1 } { \mathbb p}(n_j(\beta^{1/\alpha}d ) = k)(1-p_i)^k\log(1+\beta_i ) \\ & = p_i\sum_{k=1}^{n\lambda_i-1 } \left(\frac{\pi\beta_i^{2/\alpha}d^2}{n}\right)^k \left(1-\frac{\pi\beta_i^{2/\alpha}d^2}{n}\right)^{n\lambda_i - k-1 } \\ & \quad\quad\quad\quad\quad \times \binom{n\lambda_i-1}{k}(1-p_i)^k\log(1+\beta_i)\\ & = p_i\left(1-p_i\frac{\pi\beta_i^{2/\alpha}d^2}{n}\right)^{n\lambda_i-1}\log(1+\beta_i ) \\ & \rightarrow p_i \log(1+\beta_i ) e^{-\pi\lambda_id^2p_i\beta_i^{2/\alpha}}\end{aligned}\ ] ] in the limit @xmath28 . in order to obtain better insight into the problem at hand , a change of variables is required . we refer to the set of all points within the transmission range as the _ transmission disc_. the quantity @xmath34 is the _ average number of nodes ( tx or rx ) per transmission disc_. we often refer to it simply as the _ number of nodes per disc _ and represent it by the symbol @xmath35 assume @xmath36 is larger than a certain threshold ( we make this precise later ) . maximizing over the access probability yields @xmath37 with the optimal access probability being @xmath38 one can further optimize over the target @xmath17 so that @xmath30 is replaced by @xmath39 in the above two equations . inspection of equation ( [ eqn : one_network_thpt ] ) reveals that the optimal target @xmath17 is a function of @xmath0 alone . so if we define the quantity @xmath40 @xmath41 will be a constant , independent of @xmath36 . the quantity @xmath42 represents the _ average number of ( simultaneous ) transmissions per transmission disc_. we sometimes refer to it simply as the _ transmit density_. whereas the domain of @xmath29 is @xmath43 $ ] , the domain of @xmath42 is @xmath44 $ ] . thus we see that for @xmath36 sufficiently large , the access probability should be set such that an optimal number of transmissions per disc is achieved . what is this optimal number ? what is the optimal target @xmath17 ? for the purposes of optimizing equation ( [ eqn : one_network_thpt ] ) , define the function @xmath45 as the unique solution of the following equation @xmath46 a plot of @xmath45 is given in figure [ fig : lambda_star ] . so as to avoid confusion , note that the symbol @xmath47 represents a pre - defined function , not necessarily the same as the symbol @xmath41 , which is a variable . as equation ( [ eqn : one_network_thpt ] ) is smooth and continuous with a unique maxima , by setting it s derivative to zero we find that the optimal target @xmath17 is @xmath48 and the optimal number of transmissions per disc is @xmath49 , when @xmath36 is larger than a certain threshold . when @xmath36 is smaller than this threshold , there are nt enough tx - rx pairs to reach the optimal number of transmissions per disc , even when all of them are simultaneously scheduled . in this case the solution lies on the boundary with @xmath50 . this corresponds to the scenario where the transmission range is short relative to the node density such that tx - rx pairs function as if in isolation . it is intuitive that in this case all transmissions in the network will be simultaneously scheduled . our discussion is summarized in the following theorem . [ thm : op_access_prob ] ( optimal access probability ) for a single network operating in isolation under the random access protocol , when @xmath51 the optimal access probability is @xmath52 , where @xmath47 is given by the unique solution of equation ( [ eqn : lambda_star ] ) . the optimal target @xmath17 is @xmath53 . when @xmath54 , @xmath50 and @xmath39 is given by the unique solution to @xmath55 the region satisfying @xmath51 is referred to as the _ partial _ reuse regime . the complement region is referred to as the _ full reuse _ regime . note the optimal access probability of the above theorem is equivalent to the results of section iv.b in @xcite , and those discussed under the title _ `` maximum achievable spatial throughput and tc '' _ on page 4137 of @xcite . now we perform the same computation for the case where both networks operate on the same unlicensed band . in this case there is both _ intra - network _ and _ inter - network _ interference . it is straightforward to extend the above analysis to show that for network @xmath10 @xmath56 in the limit @xmath57 . for a given @xmath58 the first network can optimize @xmath59 and @xmath60 , and vice - versa . that is each network can iteratively adjust its access probability and target @xmath17 in response to the other networks . in this sense a game can be defined between the two networks . a strategy for network @xmath10 is a choice of @xmath61 $ ] and @xmath62 . its payoff function ( also referred to as _ utility function _ ) is the limiting form of @xmath63 times @xmath36 , @xmath64 here we have scaled the throughput by @xmath36 to emphasize the simple form of the payoff functions . at first glance this setup seems desirable but there is a redundancy in the way the strategy space has been defined . the problem is that the variable @xmath30 only appears in @xmath65 and thus should be optimized over separately rather than being included as part of the strategy . this leads to the following game setup . [ def : ne ] ( random access game ) a strategy for network @xmath10 in the random access game is a choice of @xmath66 $ ] . the payoff functions are @xmath67 the above formulation is intuitively appealing as a networks choice of access probability constitutes its entire strategy . if we could explicitly solve the maximization problems , the variables @xmath30 would be removed altogether . when @xmath59 and @xmath58 are large this can be done and @xmath68 but in general it is not possible . instead , since we are only interested in analyzing the nash equilibrium ( n.e . ) or equilibria of this game , we do the following . observe that the objective function within the maximization is smooth and continuous . this enables the order of maximization to be swapped . that is , for a given @xmath58 , we first maximize over @xmath59 in equation ( [ eqn : utility_fns1 ] ) and then over the @xmath60 . likewise for equation ( [ eqn : utility_fns2 ] ) . the benefit of this approach is that the maximizing @xmath42 can be explicitly expressed as a function of @xmath30 . this was demonstrated earlier for the single network scenario . the resulting expressions are @xmath69 the set of n.e . of the above game and their corresponding values of @xmath70 and @xmath71 are identical to those of the random access game . inspection of the above equations reveals a further simplification of the problem is at hand the set of n.e . of the above game are identical to the set of n.e . of the following game ( though the values of @xmath70 and @xmath71 at the equilibria may be different ) . [ def : ne ] ( transformed random access game ) a strategy for network @xmath10 in the transformed random access game is a choice of @xmath66 $ ] . the payoff functions are @xmath72 we now analyze the n.e . of the random access game by analyzing the n.e . of the transformed random access game . the first question of interest is whether or not there exists a n.e . ? it turns out a unique n.e . always exists but its nature depends crucially on the pathloss exponent . there are two _ modes _ , @xmath73 and @xmath1 . we start with the first . [ thm : opt_p2 ] ( random access n.e . for @xmath74 ) for @xmath75 the unique n.e . occurs at @xmath76 , and @xmath77 defined by either the solution of @xmath78 or @xmath79 , whichever is smaller . the n.e . described in theorem [ thm : opt_p2 ] occurs on the boundary of the strategy space . this is because for @xmath73 each network tries to set its number of transmissions per disc higher than the other ( see the proof of the theorem ) . the equilibrium is then only attained when at least one network has maxed out and scheduled all of its transmissions simultaneously . the n.e . can be better understood when @xmath80 corresponding to the case in which transmissions span several intermediate nodes . [ thm : asymp_soln ] ( random access n.e . for @xmath74 and @xmath80 ) in the limit @xmath81 the n.e . occurs at @xmath82 this result stems from using the limiting form @xmath83 as @xmath84 in the utility functions @xmath70 and @xmath71 , as was done in equations ( [ eqn : appr_uf1 ] ) and ( [ eqn : appr_uf2 ] ) . from it we see that if the denser network has more than @xmath85 times as many nodes as its rival , the n.e . will correspond to partial reuse , i.e. the denser network will only occupy a fraction of the total available bandwidth . this is in stark contrast to the case of competing _ individual transmissions _ where the n.e . typically corresponds to a full spread , i.e. both competing links spread their power evenly across the entire bandwidth . the limit result of theorem [ thm : apx_soln ] is plotted in figure [ fig : lambda2_star ] as a dashed line . ) for @xmath86 . value @xmath77 is equal to the minimum of this line and @xmath87 . the limiting solution used in theorem [ thm : apx_soln ] is plotted as a dashed line . ] we now investigate the average throughput at equilibrium for the mode @xmath73 . we define the metric @xmath88 this quantity has a natural interpretation . recall @xmath89 is the average throughput per tx - rx pair and @xmath36 is the average number of tx - rx pairs per transmission disc in network @xmath10 . thus @xmath90 is the _ average throughput per transmission disc _ in network @xmath10 . this is the average number of bits successfully received in network @xmath10 within an area of size @xmath91 per time slot , per d.o.f .. the quantity @xmath92 is then the average throughput per transmission disc in the system , that is , the average number of bits successfully received _ in both networks _ within an area of size @xmath91 per time slot , per d.o.f .. [ thm : asymp_util ] in the limit @xmath93 @xmath94 where @xmath95 and @xmath96 . the important property of this result is that as the number of nodes per transmission disc increases , @xmath92 decreases roughly like @xmath97 . let us compare this to the average throughput per transmission disc in the cooperative case , that is when the two networks behave as if they were a single network with @xmath98 nodes per disc . from equation ( [ eqn : one_network_thpt ] ) this average throughput per disc is @xmath99 which is independent of the number of nodes per disc . thus as the number of nodes per disc grows , so does the price of anarchy @xmath100 for @xmath1 the n.e . behavior is different . whereas for @xmath73 the solution always lies on the boundary , for @xmath1 it typically does not . [ thm : a_ge_4 ] ( random access n.e . for @xmath101 ) for @xmath101 the unique n.e . occurs at @xmath102 if @xmath103 , otherwise @xmath76 and @xmath77 is defined by either the solution of equation ( [ eqn : opt_p2 ] ) or @xmath87 , whichever is smaller . a plot of @xmath104 versus @xmath0 is given in figure [ fig : lambda_prime ] . the condition @xmath103 corresponds to network @xmath105 having more than @xmath104 nodes per transmission disc . we refer to this as the _ partial / partial reuse _ regime . the interpretation of theorem [ thm : a_ge_4 ] is that for @xmath1 in the partial / partial reuse regime , the solution lies in the strict interior of the strategy space . this is because on the boundary of the space network @xmath10 can improve its throughput by undercutting the transmit density of network @xmath18 , i.e. setting @xmath106 . the symmetry of the n.e . ( @xmath107 ) then follows by observing the utility functions are symmetric and the solution is unique . and the intersection of the full / full reuse regime with the axes always occurs at @xmath108 and @xmath109.,title="fig : " ] and the intersection of the full / full reuse regime with the axes always occurs at @xmath108 and @xmath109.,title="fig : " ] and the intersection of the full / full reuse regime with the axes always occurs at @xmath108 and @xmath109.,title="fig : " ] and the intersection of the full / full reuse regime with the axes always occurs at @xmath108 and @xmath109.,title="fig : " ] and the intersection of the full / full reuse regime with the axes always occurs at @xmath108 and @xmath109.,title="fig : " ] and the intersection of the full / full reuse regime with the axes always occurs at @xmath108 and @xmath109.,title="fig : " ] there is a cooperative flavor to this equilibrium in that both networks set their transmission densities to the same level , and this level is comparable to the optimal single network density @xmath45 . moreover the equilibrium level does not grow with the number of nodes per transmission disc , as it does for @xmath73 . actual cooperation between networks corresponds to setting the access probability based on equation ( [ eqn : p_star ] ) , taking into account that the effective node density is @xmath110 . thus the cooperative solution is @xmath111 under cooperation the average throughput per transmission disc is ( from equation ( [ eqn : one_network_thpt ] ) ) @xmath112 under cooperation in the partial / partial reuse regime it is @xmath113 , the price of anarchy depends only on the pathloss exponent in the partial / partial reuse regime . ] the price of anarchy is the ratio of these two quantities ( @xmath114 ) and is plotted in figure [ fig : poa ] . comparing the two modes we see that whereas for @xmath73 the price of anarchy grows in an unbounded fashion with the number of nodes per transmission disc , for @xmath1 the price of anarchy in the partial / partial reuse regime is a constant depending only on @xmath0 . we now summarize the equilibria results . there are three regimes . 1 . _ full / full reuse _ + - @xmath115 and @xmath116 + - both networks schedule all transmissions 2 . _ full / partial reuse _ + - @xmath115 and @xmath117 + - denser network schedules all transmissions , sparser schedules only a fraction 3 . _ partial / partial reuse _ + - @xmath118 + - both networks schedule only a fraction of their transmissions in the full / full reuse regime @xmath119 . in the full / partial reuse regime the sparser network sets @xmath76 and the denser network sets @xmath77 as the solution to equation ( [ eqn : opt_p2 ] ) . in the partial / partial reuse regime @xmath120 . the regimes are essentially distinguished by which boundary constraints are active . for @xmath75 the partial / partial reuse regime is not accessible . figure [ fig : regimes ] provides an illustrated means for determining which regime the system is in , for a range of values of the pathloss exponent . in these plots we consider all values of @xmath79 and @xmath87 , not just those satisfying @xmath121 . notice that as @xmath122 the entire region corresponds to the full / full reuse regime , for @xmath123 almost the entire region corresponds to the full / partial reuse regime and for @xmath124 the entire region corresponds to the partial / partial reuse regime . in this section we examine the case where tx - rx pairs tailor their communication rates to suit instantaneous channel conditions , sending at rate @xmath125 during the @xmath22th time slot . various protocols can be used to enable tx - rx pairs to estimate their @xmath126 . consider first the single , isolated network scenario . the expected time - averaged rate per user is now @xmath127 as before , the rate is both time - averaged over the interference and averaged over the geographic distribution of the nodes . the @xmath17 is the instantaneous value observed by a given rx node and is distributed according to @xmath128 where the variable @xmath129 denotes the distance to the nearest interferer . thus @xmath130 in the limit @xmath57 . changing variables and optimizing we have @xmath131 define @xmath132 as the maximizing argument of the unconstrained version of the above optimization problem , or more specifically as the unique solution to @xmath133 the function @xmath132 is plotted in figure [ fig : lambda_prime ] . then @xmath134 from this we see that the solution for the variable - rate case is the same as the fixed - rate solution , differing only by substitution of the function @xmath132 for @xmath45 . now we turn to the case of two competing wireless networks . using an approach similar to the one above it can be shown that @xmath135 in this way we can define the game between the two networks like so . ( variable rate random access game ) a strategy for network @xmath10 in the variable rate random access game is a choice of @xmath136 $ ] . the payoff functions are @xmath137 from the above definition we see that the fixed - rate game is derived from the variable - rate game by merely applying a step - function lower bound to the players utility functions , with the width of the step - function optimized , i.e. @xmath138 a plot comparing the expression on the left as a function of @xmath139 , to the expression on the right as a function of @xmath139 , for @xmath123 , is presented in figure [ fig : vr_vs_fr ] . the figure suggests that both expressions share a similar functional dependency on @xmath139 . it is therefore natural to wonder whether , as a consequence of this close relationship , the n.e . of the variable - rate game bears any relationship to the n.e . of the fixed - rate game ? . the y - axis represents @xmath140 . ] as in the fixed - rate game , the utility functions of the variable - rate game can be explicitly evaluated when @xmath59 and @xmath58 are large yielding @xmath141 comparing with equations ( [ eqn : utility_fns1 ] ) and ( [ eqn : utility_fns2 ] ) we see that for large @xmath142 , the utility functions of the variable - rate game have exactly the same functional dependency on @xmath142 as the utility functions of the fixed - rate game , differing only in an @xmath0-dependent constant . these constants are plotted in figure [ fig : consts ] . the plots illustrate the benefit in total system throughput that stems from playing the variable - rate game in place of the fixed - rate game . -dependent constants . these constants are plotted above . for the variable - rate game the constant is @xmath143 versus @xmath144 for the fixed - rate game . ] as anticipated by the above discussion , the n.e . behavior of the variable - rate game parallels that of the fixed - rate game . the same two modes are present , @xmath73 and @xmath1 . these give rise to the same three spreading regimes , the only difference being that the boundaries delineating them are shifted slightly . values @xmath145 in each regime take on a similar form . [ thm : vr_soln ] the variable - rate random access game has a unique n.e . @xmath145 which lies in one of three regions . let @xmath146 be the unique solution of @xmath147 for @xmath101 , and equal to positive infinity for @xmath148 . * ( full / full reuse ) if @xmath149 and @xmath150 the unique solution over @xmath151 of @xmath152 then @xmath153 . * ( full / partial reuse ) if @xmath149 and @xmath154 the unique solution of equation ( [ eqn : vr_thm ] ) then @xmath155 and @xmath77 is equal to this unique solution . * ( partial / partial reuse ) if @xmath156 then @xmath157 . a regime map is provided in figure [ fig : vr_regimes ] . as is evident from the above theorem , it is not possible to characterize the behavior of the n.e . for the variable - rate game as explicitly as for the fixed - rate game . this is in part due to the more complex representation of the utility functions in terms of integrals , and in part due to the fact that the the function @xmath146 can not be represented in terms of the function @xmath132 , as in the case of the fixed - rate game , where one function equals the square - root of the other evaluated at @xmath158 . for large @xmath79 however , we can use the approximation adopted in theorem [ thm : apx_soln ] to explicitly characterize the behavior of the n.e . in the full / partial reuse regime . [ thm : apx_soln_vr ] ( variable - rate random access n.e . for @xmath74 and @xmath80 ) in the limit @xmath81 the n.e . occurs at @xmath82 and @xmath132 for the variable - rate model versus the equivalent functions @xmath45 and @xmath159 for the fixed - rate model . ] thus for @xmath75 and large @xmath79 , the behavior of the n.e . in the variable - rate game is identical to that of the fixed - rate game . as discussed earlier , the values of @xmath70 and @xmath71 at equilibrium are equal to those of the fixed - rate game times a constant @xmath160 . the intuition behind our result is the following . the average throughput per link is essentially equal to the product of the fraction of time transmissions are scheduled , and the average number of bits successfully communicated per transmission . adjusting the transmit density has a linear effect on the former term , but a non - linear effect on the latter . the latter depends on the @xmath17 and the @xmath17 essentially depends on the pathloss exponent via @xmath161 when the nearest interferer is closer than the transmitter , the ratio inside the parentheses is less than one , and a large value of @xmath0 substantially hurts the @xmath17 , dragging it to near zero and causing the link capacity to drop to near zero . however , when the nearest interferer is further away than the transmitter , the ratio is greater than one and a large value of @xmath0 substantially improves the @xmath17 , resulting in a large link capacity . thus for large @xmath0 the average number of bits successfully communicated per transmission is very sensitive to whether or not the transmission disc is empty . this insensitivity for sufficiently small @xmath0 means that increasing the transmit density in network @xmath10 causes a linear increase in the fraction of time transmissions are scheduled , but has little effect on the number of bits successfully communicated per transmission , up until the point where the transmit density of network @xmath10 starts to dwarf the transmit density of network @xmath18 . thus network @xmath10 will wish to increase its transmit density until it is sufficiently larger than network @xmath18 s . likewise network @xmath18 will wish to increase its transmit density until it is sufficiently larger than network @xmath10 s . ultimately this results in either 1 . a full / full reuse solution , which occurs when the sparser network max s out and winds up simultaneously scheduling all of its transmissions , and the denser network is insufficiently dense such that its optimal transmit density based on the sparser networks choice , results in it simultaneously scheduling all of its transmissions , or 2 . a full / partial reuse solution , which occurs when the sparser network max s out and winds up simultaneously scheduling all of its transmissions but the denser network is sufficiently dense such that its optimal transmit density based on the sparser networks choice , results in it simultaneously scheduling only a fraction of its transmissions . the opposite effect occurs for sufficiently large @xmath0 , where the average number of bits successfully communicated per transmission depends critically on whether or not there is an interferer inside the transmission disc . in this scenario network @xmath10 will set its active density to a level lower than network @xmath18 s , in order to capitalize on those instances in which network @xmath18 happens to not schedule any transmissions nearby to one of network @xmath10 s receivers , resulting in the successful communication of a large number of bits . likewise network @xmath18 will set its active density to a level lower than network @xmath10 s , and the system converges to the partial / partial reuse regime . one of our initial assumptions was that all tx - rx pairs have the same transmission range @xmath11 . in this section we consider the scenario where the transmission ranges of all tx - rx pairs in the system are i.i.d . random variables @xmath162 . when the variance of @xmath162 is large , some form of power control may be required to ensure long range transmissions are not unfairly penalized . a natural form of power control involves tx nodes setting their transmit powers such that all transmissions are received at the same @xmath2 . this means transmit power scales proportional to @xmath163 . denote the distance from the @xmath164th tx node to the @xmath18th rx node @xmath165 . then the interference power from the @xmath164th tx node impinging on the @xmath18th rx node is proportional to @xmath166 . in the fixed transmission range scenario this quantity was proportional to @xmath167 . there we assumed the bulk of the interference was generated by the dominant interferer . denote the scheduled set of tx nodes at time @xmath22 by @xmath168 . this assumption essentially evoked the following approximation @xmath169 the equivalent approximation for the variable transmission range problem is @xmath170 thus for variable range transmission the dominant interferer is not necessarily the nearest to the receiver . under this assumption the @xmath17 at the @xmath18th rx node at time @xmath22 is then @xmath171 where @xmath172 is the index of the tx node that is closest to the @xmath18th receiver relative to its transmission range . let us compute the throughput for the variable transmission range model under the fixed - rate random access protocol . @xmath173 the probability the @xmath17 is greater than the threshold @xmath174 as @xmath28 . for notational simplicity let @xmath175 . if we define @xmath36 as the average number of nodes per transmission disc , where the average is taken over both the geographical distribution of the nodes _ and the distribution of the size of the transmission disc _ , i.e. @xmath176 we wind up with @xmath177 , which is the same result as the fixed - transmission range model . it is straightforward to extend the analysis to the case of two competing networks . the throughput per user in network 1 is then @xmath178 likewise for network 2 . from this we see that all results for the fixed - transmission range model extend to the variable - transmission range model by simply replacing @xmath179 by @xmath180 . in order to get a sense of the typical behavior of the players in the ( variable - rate ) random access game , and to justify the validity of the dominant interferer assumption , we simulate the behavior of the following greedy algorithm with the interference computed based on all transmissions in the network , not just the strongest . + * inputs : * @xmath181 + * outputs : * @xmath182 $ ] , for @xmath183 . + * for * @xmath184 to @xmath185 + form estimate @xmath186 form estimate @xmath187 + * if * @xmath188 @xmath189 * else * @xmath190 * end * + form estimate @xmath191 form estimate @xmath192 + * if * @xmath193 @xmath194 * else * @xmath195 * end * + * end * + each update time @xmath22 , network 1 temporarily sets its access probability to @xmath196 and measures the resulting throughput , averaged over 200 transmission times . this is denoted @xmath186 . it then repeats this measurement for an access probability of @xmath197 . this is denoted @xmath198 . it then either permanently increases its access probability to @xmath199 or permanently decreases it to @xmath200 depending on which option it estimates will lead to a higher throughput . now network 2 performs the same operation . it uses a total of 400 time slots to measure the effect of increasing versus decresing its access probability and then either sets @xmath201 or @xmath202 . if @xmath203 is small , then both networks can perform these measurement operations simultaneously without significantly affecting the outcome . the topology used in the simulations consisted of 400 tx nodes from network 1 and 200 tx nodes from network 2 , all i.i.d . uniformly distributed in a square of unit area . for each tx node , its corresponding rx node was located at a point randomly chosen at uniform from a disc of radius 0.15 . this corresponds to @xmath204 and @xmath205 . a step - size of @xmath206 was used . when computing the throughputs , in order to avoid boundary effects , only transmissions emanating from those tx nodes in the interior of the network were counted . the results for @xmath207 and @xmath208 are displayed in figure [ fig : ra_sim ] . the observed behavior corresponds to the analytical results . for the values of @xmath79 and @xmath87 used , the n.e . lies in the full / full regime for @xmath209 , the full / partial regime for @xmath210 , and the partial / partial regime for @xmath211 , as can be seen from figure [ fig : regimes ] . + + the high level conclusion from our analysis of the random access protocol , is that the nash equilibrium is cooperative in nature for a sufficiently high pathloss exponent . ideally we would like to be able to draw this conclusion for a more sophisticated class of scheduling protocols employing carrier sensing . due to the analytical intractability of the problem , we present simulation results to illustrate this effect . we assume both networks operate under the following protocol . we present a centralized version of it due to space constraints , but claim there exists a distributed version that performs identically in most cases . during the scheduling phase , each tx - rx pair is assigned a unique token at random from @xmath212 . tx nodes proceed with their transmission so long as they will not cause excessive interference to any rx node with a higher priority token . more precisely , a transmission is scheduled so long as for each rx node with higher priority , the difference between its received signal power in db and the interference power from the lower priority tx node in db , exceeds a silencing threshold @xmath213 ( @xmath214 for network 1 and @xmath215 for network 2 ) . thus a game between the two networks can be defined where the strategies are the choices of silencing thresholds @xmath216 and @xmath217 . we refer to this as the _ csma game_. the silencing threshold for the csma game essentially plays the same role as the access probability in the random access game -it determines the degree of spatial reuse . a high value of @xmath218 leads to a low density of transmissions , a low value of @xmath218 leads to a high density . we simulate the behavior that arises when both networks optimize their silencing thresholds in a greedy manner . analogously to before , we have the following algorithm . + * inputs : * @xmath181 + * ouputs : * @xmath182 $ ] , for @xmath183 . + * for * @xmath184 to @xmath185 + form estimate @xmath219 form estimate @xmath220 + * if * @xmath221 @xmath222 * else * @xmath223 * end * + form estimate @xmath224 form estimate @xmath225 + * if * @xmath226 @xmath227 * else * @xmath228 * end * + * end * + the topology used in the setup is identical to before , the only exception being that at each iteration of the algorithm , 10 old tx - rx pairs leave each network , and 10 new pairs join in i.i.d . locations drawn uniformly at random . this is to ensure sufficient averaging . in a similar fashion to before , each network estimates the effect of either increasing or decreasing the silencing threshold and then makes a permanent choice . for the same parameter values , the results of the simulation are displayed in figure [ fig : csma_sim ] . on the y - axes of these plots we have drawn the fraction of nodes simultaneously scheduled at each iteration , which we denote @xmath229 and @xmath230 , rather than the silencing thresholds @xmath213 , in order to draw a simple visual comparison with figure [ fig : ra_sim ] . for this reason there is more fluctuation in the results , as the fraction of simultaneously scheduled transmissions varies not only due to the up / down movements of the silencing thresholds , but also due to the changing topology . we conclude from these plots that for small values of @xmath0 ( namely @xmath209 ) the system converges to a competitive equilibrium , where both networks simultaneously schedule a large fraction of their transmissions , and for large values of @xmath0 ( namely @xmath210 and @xmath208 ) the system converges to a near cooperative equilibrium , where both networks schedule a small fraction of their transmissions . this work studied spectrum sharing between wireless devices operating under a random access protocol . the crucial assumption made was that nodes belonging to the same network or coalition cooperate with one another . competition only exists between nodes belonging to rival networks . it was found that cooperation between devices within each network created the necessary incentive to prevent total anarchy . for pathloss exponents greater than four , we showed that contrary to ones intuition , there can be a natural incentive for devices to cooperate to the extent that each occupies only a fraction of the available bandwidth . such results are optimistic and encouraging . we demonstrated via simulations that it may be possible to extend them to more complex operating protocols such as those that employ carrier - sensing to determine when the medium is free . more generally one wonders whether a multi - stage game capturing the system dynamics under such a protocol can be formulated , and whether the desirable properties of the single - stage game continue to hold . it would also be worthwhile investigating the incentives wireless links have to form coalitions , as in this work it was in essence assumed that coalitions had been pre - determined . the limiting expression for the average throughput is @xmath231 given a @xmath30 there is a single maximum over @xmath29 . by differentiation we have @xmath232 so @xmath233 . thus @xmath234 both of these functions have one maximum , but the maximum of the second function is always greater than the maximum of the first as it represents the solution to the unconstrained problem @xmath235 whereas the maximum of the first represents the solution to @xmath236 thus if the maximum of the second function occurs for @xmath237 , it is the maximum of the entire function , but if it occurs for @xmath238 , the maximum of the entire function is the maximum of the first function over the domain @xmath238 . by differentiation we find the maximum of the second function occurs at the unique solution of @xmath239 which is @xmath240 . thus if @xmath241 , the solution is @xmath242 and @xmath53 . if @xmath243 the solution is @xmath244 and @xmath39 equal to the unique solution of @xmath245 or @xmath246 , whichever is smaller . but as @xmath247 is a monotonically increasing function , from the definition of @xmath47 we have @xmath248 whenever @xmath243 . combining this with equation ( [ eqn:2ndfn_max ] ) and using the monotonicity of @xmath247 we see that the unique solution to equation ( [ eqn:2ndfn_max ] ) is always smaller than @xmath246 . this establishes the desired result . first we show that any n.e . must lie on the boundary of the strategy space , i.e. @xmath249 for some @xmath10 . the utility functions are smooth and continuous . differentiating @xmath70 with respect to @xmath59 yields @xmath250 consider the function @xmath251 . as @xmath252 is monotonically decreasing for @xmath253 and @xmath254 we have @xmath255 for all @xmath253 . thus for @xmath4 , @xmath256 whenever @xmath257 and similarly @xmath258 whenever @xmath259 . thus for a n.e . to occur in the interior of the strategy space we must have both @xmath260 and @xmath261 . as these conditions are mutually exclusive at least one of the constraints of the strategy space must be active at the n.e .. in essence each network is trying to set it s active density higher than the other s . eventually at least one network maxs out . first consider the case where the solution to @xmath262 occurs for @xmath263 . suppose @xmath264 . then as @xmath265 we have @xmath266 , hence @xmath267 for all @xmath59 on the interior and hence @xmath76 . now the function @xmath268 has a unique maximum for @xmath58 . this maximum satisfies @xmath269 , which is equation ( [ eqn : opt_p2_again ] ) with @xmath77 substituted for @xmath32 . but the solution equation ( [ eqn : opt_p2_again ] ) satisfies @xmath263 , so @xmath270 , a contradiction . thus the constraint @xmath271 must be inactive . suppose instead that the constraint @xmath76 is active . then by the same arguments the unique @xmath77 satisfies equation ( [ eqn : opt_p2_again ] ) . this establishes the solution and it s uniqueness , for the first case . second consider the case where the solution to equation ( [ eqn : opt_p2_again ] ) occurs for @xmath272 . then it is straightforward to check using similar arguments above , that the unique solution satisfies @xmath273 . this establishes the result . for @xmath274 the solution to equation ( [ eqn : opt_p2 ] ) only goes to infinity for @xmath93 . in this limit @xmath275 and @xmath276 if @xmath277 . otherwise , @xmath278 . computing @xmath279 produces the stated result . this follows by direct substitution . the proof of this result is more involved than the proof of theorem 2.3 . there are three regimes . first consider the joint spread regime where @xmath118 . we show that a n.e . can not occur on the boundary of the strategy space . suppose @xmath280 . then @xmath281 . as @xmath104 is the solution to the equation @xmath282 and @xmath283 is a monotonically decreasing function for @xmath284 , we have @xmath285 if @xmath286 lies on the boundary of the strategy space then @xmath287 which implies @xmath288 this in turn implies @xmath289 at equilibrium @xmath290 so @xmath291 a contradiction . thus @xmath292 . now assume @xmath293 . by assumption @xmath294 so @xmath295 . by repeating the same arguments we can generate the same style of contradiction and thus @xmath296 . this establishes that a n.e . can not occur on the boundary of the strategy space . in essence each network is trying to undercut the active density of the other . this drags the equilibrium away from the boundary . now we establish any n.e . must be symmetric , i.e. @xmath107 . suppose a n.e . @xmath145 with @xmath297 exists . then as it must lie on the interior of the strategy space and as the utility functions are symmetric , @xmath298 must also be a n.e .. on the interior of the strategy space the n.e . criterion is @xmath299 and so the function @xmath300 is monotonically increasing in @xmath58 . but this implies we can not have n.e . at both @xmath145 and @xmath298 , a contradiction . thus @xmath107 . by differentiating the utility functions this implies that at any n.e . @xmath286 satisfies @xmath301 with @xmath302 . but this is equivalent to @xmath303 . thus the n.e . is unique and occurs at @xmath304 . next consider the partial spread and full spread regimes where @xmath115 . we first show that @xmath76 . suppose @xmath305 . then @xmath306 which implies @xmath307 at equilibrium @xmath308 so @xmath309 but this in turn implies @xmath310 which in conjunction with the equilibrium condition @xmath311 implies @xmath312 , a contradiction . thus @xmath76 . now we can solve for @xmath77 to conclude that @xmath77 is the unique solution to equation ( [ eqn : opt_p2 ] ) or @xmath87 , whichever is smaller . this concludes the proof . we first tackle the full spread and partial spread regimes . it is shown in lemma [ lem:4 ] in the appendix that @xmath146 is undefined for @xmath148 and recall @xmath146 is defined to be positive infinity for @xmath101 . consider the case where @xmath313 . we show that @xmath280 . suppose the contrary , that @xmath314 . then @xmath315 . define the function @xmath316 for @xmath317 and @xmath318 positive . in lemma [ lem:1 ] in the appendix it is shown that @xmath319 is a monotonically decreasing function in @xmath320 . by rearranging equation ( [ eqn : lambda_doubleprime ] ) one can check that @xmath321 . thus @xmath322 . for a given @xmath58 it is shown in lemma [ lem:2 ] in the appendix that the utility function @xmath323 is a smooth continuous function of @xmath59 with a unique maximum ( and likewise for @xmath71 given @xmath59 ) . as @xmath314 the maximum with respect to @xmath59 occurs at @xmath324 . by rearranging equation ( [ eqn : vr_thm ] ) one can check that this condition is equivalent to @xmath325 . this means @xmath326 . in lemma [ lem:2 ] we show that @xmath327 is a monotonically increasing function in @xmath318 given @xmath317 . thus we have @xmath328 and so also @xmath329 and @xmath330 . thus @xmath331 . as by assumption @xmath332 , we have @xmath333 and so the maximum of @xmath71 occurs at @xmath334 . this means @xmath335 which implies @xmath312 . this is a contradiction . thus we must have @xmath76 at a n.e .. by maximizing over @xmath58 via differentiation of @xmath71 , we see that @xmath77 equals the solution of ( [ eqn : vr_thm ] ) or @xmath87 whichever is smaller . lemma [ lem:2 ] establishes the solution of ( [ eqn : vr_thm ] ) always exists and is unique . now consider the case where @xmath156 . we first show that a n.e . can not occur on the boundary of the strategy space . suppose @xmath280 . then @xmath336 . this implies @xmath337 . as @xmath280 the maximum of @xmath70 occurs at @xmath338 for a given @xmath58 . this means @xmath339 , thus @xmath340 . we also then have @xmath341 . from the optimality condition for network 2 we then have @xmath342 . this means @xmath343 which implies @xmath344 . this is a contradiction . thus we must have @xmath305 . as @xmath345 we can repeat the argument for @xmath77 to conclude that we must also have @xmath346 . this proves a n.e . can only occur on the interior of the strategy space . now we establish any n.e . must be symmetric , i.e. @xmath107 . suppose a n.e . @xmath145 with @xmath297 exists . then as it must lie on the interior of the strategy space and as the utility functions are symmetric , @xmath298 must also be a n.e .. on the interior of the strategy space the n.e . criterion is @xmath299 and so the function @xmath300 is monotonically increasing in @xmath58 by lemma [ lem:3 ] . but this implies we can not have n.e . at both @xmath145 and @xmath298 , a contradiction . thus @xmath107 . finally one can verify that @xmath347 is a n.e . by differentiating the utility functions . thus the unique n.e . is @xmath157 . in essence what is going on here is that in the absence of strategy space constraints , when @xmath348 , network @xmath10 wants to set @xmath349 and when @xmath350 network @xmath10 wants to set @xmath106 . thus the natural equilibrium is at @xmath351 . the problem for @xmath4 is @xmath146 is infinite and the sparser network winds up maxing out at @xmath280 . when @xmath1 the function @xmath146 is finite and it is possible to have @xmath352 , i.e. both networks have a sufficiently high density of nodes so as not to be constrained by the strategy space . in this case they get to set their access probabilities so as to achieve the natural equilibrium . [ lem:1 ] the function @xmath319 is monotonically decreasing in @xmath320 . as the integral is well - defined for all positive @xmath59 and @xmath58 , the function is smooth and continuous by inspection . to see that a unique maximum exists set the derivative to zero to obtain @xmath364 . for fixed @xmath365 it is straightforward to show @xmath366 is monotonically decreasing in @xmath42 using arguments similar to those in lemma [ lem:1 ] . for @xmath367 we find @xmath368 and for @xmath369 we find @xmath370 which is always less than 1 for @xmath274 . thus there always exists a single @xmath41 satisfying @xmath371 and hence a unique maximum always exists . @xmath146 is the solution to @xmath321 . the function @xmath319 is a monotonically decreasing in @xmath320 by lemma [ lem:1 ] . by taking @xmath374 we find @xmath375 and by taking @xmath376 we find @xmath377 . thus when @xmath148 there is no @xmath320 for which @xmath378 and hence @xmath146 is undefined . when @xmath101 there is a single @xmath320 at which @xmath319 crosses the value 1 and hence @xmath146 is uniquely defined . chung , s. kim , j. lee , j.m . cioffi , `` a game - theoretic approach to power allocation in frequency - selective gaussian interference channels , '' _ proc . of ieee international symposium on information theory _ , pp . 316 - 316 , july 2003 . n. jindal , j. g. andrews , s. weber , optimizing the sir operating point of spatial networks , _ workshop on information theory and its applications , u.c . san diego _ , available at arxiv : cd.it/0702030v1 , feb 2007 . m. h. manshaei , m. flegyhzi , j. freudiger , j .- hubaux , p. marbach , `` spectrum sharing games of network operators and cognitive radios , '' _ cognitive wireless networks : concepts , methodologies and visions _ , springer , 2007 . f. zuyuan , b. bensaou,``fair bandwidth sharing algorithms based on game theory frameworks for wireless ad - hoc networks , '' _ proc . 23rd annual joint conference of the ieee computer and communications societies ( infocom ) _ , vol . 1284 - 1295 , mar .

we consider the problem of two wireless networks operating on the same ( presumably unlicensed ) frequency band . pairs within a given network cooperate to schedule transmissions , but between networks there is competition for spectrum . to make the problem tractable , we assume transmissions are scheduled according to a random access protocol where each network chooses an access probability for its users . a game between the two networks is defined . we characterize the nash equilibrium behavior of the system . three regimes are identified ; one in which both networks simultaneously schedule all transmissions ; one in which the denser network schedules all transmissions and the sparser only schedules a fraction ; and one in which both networks schedule only a fraction of their transmissions . the regime of operation depends on the pathloss exponent @xmath0 , the latter regime being desirable , but attainable only for @xmath1 . this suggests that in certain environments , rival wireless networks may end up naturally cooperating . to substantiate our analytical results , we simulate a system where networks iteratively optimize their access probabilities in a greedy manner . we also discuss a distributed scheduling protocol that employs carrier sensing , and demonstrate via simulations , that again a near cooperative equilibrium exists for sufficiently large @xmath0 .

several correlations have been identified among the intrinsic properties of the ( small ) population of grbs with measured redshifts @xmath7 . in particular two spectral correlations have been recently discussed in the literature : i ) the `` amati correlation '' between the energy @xmath1 where most of the emission is radiated and the total emitted energy ( isotropic equivalent ) @xmath2 ( amati et al . 2002 - a02 hereafter ; lloyd & ramirez ruiz 2002 ) ; ii ) the `` ghirlanda correlation '' between @xmath8 and the collimation corrected energy @xmath4 ( ghirlanda , ghisellini & lazzati 2004 - ggl04 hereafter ) . it is important to notice that these correlations refer to the _ time integrated _ spectral properties of grbs . this is true for both @xmath9 and for the spectral indices required to calculate the rest frame bolometric @xmath2 and @xmath4 . however , time resolved spectral analysis of large samples of bursts ( e.g. ford et al . 1995 ; preece et al . 2000 ; ghirlanda , celotti , ghisellini 2002 ) have proved that the grb spectrum evolves in time during the prompt emission phase . the spectral evolution is different among different grbs ( e.g. ford et al . 1995 ) and not clearly linked to other grb global parameters ( e.g. duration , number of peaks , peak flux ) . this spectral evolution may be revealing of the time variation of the parameters of the radiative process(es ) acting in grbs ( e.g. liang & kargatis 1996 ) and/or of the relativistic properties of the emitting outflow ( e.g. ryde & petrosian 2002 ) . in order to understand the origin of such correlations it is thus compelling to determine whether they are representing global energetics characteristics or they hold for and are dominated by the time resolved spectral properties , as expected if determined by the emission process(es ) . one obvious possibility is to test them against the peak luminosity , well defined for all bursts with known @xmath7 ( e.g. liang , dai & wu 2004 ) . this issue has been recently considered by yonetoku et al . 2004 ( y04 , hereafter ) . with a sample of 12 grbs of known @xmath7 they found that @xmath10 . this correlation appeared to be tighter ( but with similar slope ) than the @xmath1@xmath11 correlation , as originally found by a02 . note that the y04 analysis adopts @xmath1 and the spectral indices of the time integrated spectrum and not the spectral properties at the peak flux . in this letter we first re examine the @xmath1@xmath0 correlation ( i.e. the yonetoku correlation " ) with an enlarged sample of 22 grbs with spectroscopically measured @xmath7 and published spectral properties . for 15 out of these 22 grbs we have an estimate of their jet opening angle @xmath12 ( ggl04 ) . we can thus calculate the collimation corrected peak luminosity @xmath3 and verify if there exists the equivalent of the ghirlanda correlation namely @xmath3 replacing @xmath13 ( sec . then we consider a much larger sample of 442 grbs with @xmath7 estimated through the lag luminosity correlation ( band , norris & bonnel 2004 - bnb04 hereafter ) to test if the yonetoku correlation still holds for this whole sample ( sec . 3 ) . in sec . 4 , by means of this same sample , we also study the relation between @xmath14 and @xmath15 , ( i.e. using spectral parameters at the peak of the flux ) , to check whether this correlation is tighter than the yonetoku one and we discuss the differences between the two . we find that the ghirlanda correlation has a smaller scatter than the corresponding @xmath1@xmath16 correlation . we give an interpretation of this result in sec . 5 and draw our conclusions in the final sec . 6 . in this paper we adopt a standard @xmath17cdm cosmology with @xmath18 , @xmath19 and @xmath20 . the bolometric @xmath21ray luminosity can be defined once the prompt emission spectrum and the redshift @xmath7 of the source are known . grb spectra are typically described by the band function @xmath22 ( band et al . 1993 ) , parameterized by low and high energy power laws ( of photon indices @xmath23 and @xmath24 , respectively ) and by peak energy @xmath1 in the @xmath25 representation . the burst emission varies on short timescales ( e.g. ramirez ruiz & fenimore 1999 ) and no universal temporal profile describes the `` zoology '' of burst light curves ( e.g. norris et al . 1996 ) . however , in most cases , a dominating peak , with flux @xmath26 integrated in the observed energy band , can be identified in the prompt emission light curve . the rest frame , bolometric ( e.g. 110@xmath27 kev ) , isotropic peak luminosity , including the redshift energy band correction , follows straightforwardly . [ corr ] in tab . 1 we report the peak luminosities of the 29 grbs examined by ggl04 , computed assuming the time integrated spectrum of each grb ( as from tab . 1 in ggl04 ) . no published spectrum was found for grb 011121 ( detected by @xmath28sax ) and this is no further considered . @xmath1 versus @xmath0 for the these grbs are shown in fig . 1 ( blue symbols ) . we omit upper / lower limits except for the two x ray flashes with measured @xmath7 . note that the underluminous grb 980425 , associated with sn 1998bw , and grb031203 , associated with sn 2003lw , are major outliers for both the yonetoku and the amati correlations . the statistical results for the correlations are reported in tab . 2 , together with the corresponding best fitting power - law parameters ( weighting for the errors on both coordinates ) . the highly significant correlation has slope similar to that found by y04 with 12 grbs . the distribution of the scatter measured along the correlation ( i.e. the distances of the data points from the fitting line ) of the 22 grbs is shown in fig . 2 ( red hatched histogram ) . a gaussian fit ( red solid line ) to the distribution yields a scatter comparable to that of the 23 grb in the @xmath1@xmath2 plane ( ghirlanda , ghisellini & firmani ( 2005 ) - ggf05 - and black dashed line in fig . 2 ) . [ corr ] for 15 out of the 22 grbs listed in tab . 1 we can correct their isotropic luminosity @xmath29 for the jet opening angle @xmath30 ( tab . 2 in ggl04 ) , i.e. @xmath31 , with a corresponding error given by : @xmath32 the red symbols in fig . 1 define the @xmath16@xmath9 correlation . again all the statistical parameters are reported in tab . the scatter of the best fit correlation ( dashed red line in fig . 1 ) decreases with respect to that using @xmath0 a trend similar to that found going from @xmath2 to @xmath13 ( ggl04 and ggf05 ) . as discussed by ggf05 in relation to the amati correlation , also the scatter of the yonetoku correlation found here can be interpreted as due to the distribution of jet opening angles . note , however , that the scatter in the @xmath1@xmath16 correlation is larger than that of the ghirlanda correlation @xmath33@xmath4 . this fact will be discussed in sec . the original amati correlation was found with 9 @xmath28sax grbs with known @xmath7 . through a redshift independent test , nakar & piran ( 2004 ) and band & preece ( 2005 ) claimed that the larger batse sample is inconsistent ( at 40% and 88% level , respectively ) with the original amati correlation . however , ggf05 ( see also ggl04 ) have confirmed the above correlation ( but finding a larger scatter ) using a sample of 23 bursts with measured @xmath7 as well as using a sample of hundreds grbs with pseudo @xmath7 . an even more general conclusion , i.e. the consistency of the above correlations with the entire batse long bursts sample , has been derived by bosnjak et al . ( 2005 ) . the same test of ggf05 can be performed for the @xmath33@xmath0 correlation found in sec . 2 . more importantly , it is worth to investigate if its scatter and slope change using this much larger sample . to this aim we consider the same sample defined in ggf05 , which comprises 442 grbs with pseudo @xmath7 [ estimated by bnb04 through the lag luminosity relation ] and known peak energy of the _ time integrated spectrum _ ( found by y04 ) . since the photon spectral indices are not given in y04 , in order to compute @xmath34 we assume typical values , i.e. @xmath35 , @xmath36 ( see e.g. preece et al . 2000 ) . in fig . 3 we show these 442 grbs ( black crosses ) in the rest frame @xmath1 vs @xmath29 plane , and in fig . 2 we show the distribution of the scatter of the 442 points around this correlation ( blue histogram in fig . 2 ) together with its gaussian fit ( black solid line in fig . this scatter is only slightly larger than that defined by the 22 grbs with measured @xmath7 ( red hatched histogram and red solid line in fig . 2 ) , and the slope of the correlations is similar ( see tab . 2 ) . for comparison with what found for the amati correlation by ggf05 , fig . 2 also reports the scatter distribution for the @xmath33@xmath2 relation with the same samples of 23 and 442 grbs ( dot dashed red and black dashed line , respectively ) . as already mentioned , the scatter of the yonetoku correlation for the 442 grbs can be interpreted as due to the distribution of the jet opening angles . assuming that the @xmath9@xmath16 correlation has a smaller scatter than the yonetoku one , we can estimate the jet opening angle distribution for the 442 grbs : we find a lognormal with a peak at @xmath37 , i.e. consistent with that found in ggf05 . to the aim of investigating the spectral correlations at the peak of the prompt emission , the most correct approach would be to analyze the spectrum of each grb , time resolved at the burst peak . this would allow to derive a peak spectral energy @xmath6 and a luminosity ( from the spectrum at the peak of the burst ) @xmath5 which , in general , might be different from the analogous integrated quantities . given that the grbs listed in tab . 1 were detected by different satellites and that the data are public only for batse , we can investigate the @xmath6@xmath5 correlation only with the sample of 442 grbs with pseudo @xmath7 . for these , in fact , mallozzi et al . ( 1998 ) provide the spectral parameters of the peak spectrum , derived by integrating the grb signal for @xmath38 2 sec around the light curve peak , and bnb04 report the peak flux corresponding to the same peak spectrum . the sample of 442 grbs allows a direct comparison with the results obtained in ggf05 . however , we here exclude a few bursts because either their @xmath39 is below the batse @xmath40 kev energy threshold ( 7 cases ) or @xmath41 is not constrained by the spectral fit ( 11 cases with @xmath42 ) . [ corr ] we report in fig . 4 the remaining 424 grbs with pseudo-@xmath7 . also in this case we find a strong correlation with a scatter consistent with that obtained adopting @xmath29 ( sec . 3 ) , and a slightly flatter slope . in other words , the peak energy and luminosity at the peak are correlated , but the correlation is not significantly tighter than the yonetoku correlation ( see tab . in sec . 2 we have derived the equivalent of the ghirlanda correlation with the peak luminosity , i.e. @xmath9@xmath16 . this correlation ( red symbols in fig . 1 ) has a scatter a factor 1.7 larger than that of the ghirlanda correlation ( for the same grbs ) . this implies that time integrated quantities correlate better than time resolved ( instantaneous " ) ones at the peak of the emission . one possible reason can be envisaged by comparing the peak luminosity @xmath0 as a function of the isotropic energy @xmath2 for the sample of 15 grbs of measured @xmath7 and jet opening angle ( fig . the two quantities are correlated , but with a considerable scatter , which is comparable to the scatter of the @xmath33@xmath16 correlation : in the insert of fig . 5 the gaussian fits to the scatter distributions of the @xmath0@xmath2 ( @xmath43 , black line ) and the @xmath9@xmath16 correlation ( @xmath44 , red line ) are reported . note that in this case the scatter corresponds to the ` horizontal ' distance of the points from the fitting line . the smaller scatter of the ghirlanda correlation with respect to the @xmath1@xmath16 one can be then ascribed to the fact that @xmath3 has a larger spread with respect to @xmath13 . interestingly , this might be related to @xmath13 being a time integrated quantity , better representing the total kinetic energy of the fireball , which is the quantity involved in the derivation of the jet opening angle ( e.g. sari , piran & halpern 1999 ) . on the contrary , @xmath3 might be more subject to local and temporal fluctuations in the fireball , not representative of the global energetics . [ corr ] [ cols= " < , < , < , < , < , < , < " , ] we derived the @xmath9@xmath0 correlation with the current largest available sample of 22 grbs with known @xmath7 and well determined spectral properties ( ggl04 ) . this correlation has a slope 0.51 , i.e. similar to that proposed by y04 , although its scatter is much larger than they originally found with 12 grbs . the scatter is instead comparable with what ggf05 found for the amati correlation using the same sample of grbs . using the 442 grbs with pseudo@xmath7 we still find a strong correlation , with similar scatter and slightly flatter slope than those found with the 22 grb of measured @xmath7 . we then considered the robustness of correlations for quantities calculated at the peak of the emission , with respect to time integrated properties . the former , in particular @xmath45 vs @xmath46 , results in a correlation equally tight to that involving integrated quantities . correcting @xmath47 for collimation , we found that the corresponding @xmath1@xmath16 correlation has a slope flatter than the ghirlanda correlation ( 0.57 vs 0.7 ) and a larger scatter ( 0.17 vs 0.1 ) . the larger scatter might be ascribed to the fact that the peak luminosity is less representative of the global energetics of the burst , which in turn is adopted to represent the total kinetic energy of the fireball and thus estimate the jet opening angle ( e.g. sari et al . the italian miur and inaf are acknowledged for funding by g. ghirlanda , g. ghisellini ( cofin grant 2003020775_002 ) , ac and zb . amati , l. et al . 2002 , a&a , 390 , 81 band , d.l . , 1993 , apj , 413 , 281 band , d.l . & preece , r.d . , 2005 , subm . to apj ( astro ph/0501559 ) ( bp05 ) band , d.l . , norris , j.p . & bonnell , j.t . , 2004 , apj , 613 , 484 ( bnb04 ) bosnjak , z. , celotti , a. , longo , f. , barbiellini , g. , 2005 , subm . to mnras ( astro ph/0502185 ) firmani , c. , ghisellini , g. , ghirlanda , g. & avila reese , v. , 2005 mnras ( letters ) , in press ( astro ph/0501395 ) ford l. a. et al . , 1995 , apj , 439 , 307 frontera , f. et al . , 2001 , apj 550 , l47 ghirlanda , g. , celotti a. & ghisellini g. , 2002 , a&a , 393 , 409 ghirlanda , g. , ghisellini , g. & lazzati , d. , 2004 , apj , 616 , 331 ( ggl04 ) ghirlanda , g. , ghisellini , g. & firmani , c. , 2005 , subm . to mnras , ( astro ph/0502186 ) ( ggf05 ) jimenez , r. , band , d.l . & piran , t. , 2001 , apj , 561 , 171 liang , e.p . & kargatis , v.e . , 1996 , nature , 381 , 49 liang e. , dai z. & wu x. f. , 2004 , apj , 606 , l29 lloyd ronning , n.m . & ramirez - ruiz e. , 2002 , apj , 576 , 101 . mallozzi , r.s . , et al . , 1998 , in gamma ray bursts , 4th huntsville symposium . proceedings 428 , eds . c. meegan , r. preece and t. koshut ( aip : woodbury , ny ) , 273 nakar , e. & piran , t. , 2004 , subm . to apj , astro ph/0412232 ( np04 ) norris , j.p . 1996 , apj , 301 , 213 piro , l. et al . , 2004 , apj , in press ( astro ph/0412589 ) preece , r. et al . , 2000 , apjs , 126 , 19 price , r. et al . , 2002 , apj , 573 , 85 ramirez ruiz , e. & fenimore , e. , 1999 , a&a , 138 , 521 ryde , f. & petrosian , v. , 2002 , apj , 578 , 290 sakamoto , t. et al . , 2004 , apj subm . ( astro ph/0409128 ) sari , r. , piran , t. , & halpern , j.p . , 1999 , apj 524 , l43 sazonov , s. yu . ; lutovinov , a. a. & sunyaev , r. a. , 2004 , nature , 430 , 646 yonetoku , d. et al . 2004 , apj , 609 , 935 ( y04 ) wall , j. v. & jenkins c. r. , 2003 , practical statistics for astronomers , cambridge university press .

we derive the peak luminosity peak energy ( @xmath0@xmath1 ) correlation using 22 long gamma ray bursts ( grbs ) with firm redshift measurements . we find that its slope is similar to the correlation between the time integrated isotropic emitted energy @xmath2 and @xmath1 ( amati et al . 2002 ) . for the 15 grbs in our sample with estimated jet opening angle we compute the collimation corrected peak luminosity @xmath3 , and find that it correlates with @xmath1 . this has , however , a scatter larger than the correlation between @xmath1 and @xmath4 ( the time integrated emitted energy , corrected for collimation ; ghirlanda et al . 2004 ) , which we ascribe to the fact that the opening angle is estimated through the global energetics . we have then selected a large sample of 442 grbs with pseudo redshifts , derived through the lag luminosity relation , to test the existence of the @xmath0@xmath1 correlation . with this sample we also explore the possibility of a correlation between time resolved quantities , namely @xmath5 and the peak energy at the peak of emission @xmath6 . [ firstpage ] gamma rays : bursts cosmology : observations

the anterior and intermediate lobes of the pituitary gland arise embryologically from rathke 's pouch . inadequate pouch obliteration results in cysts or cystic remnants at the interface between the anterior and posterior pituitary lobes , found in about 20% of pituitary glands at autopsy . rathke 's cleft cysts ( rcc ) are usually asymptomatic , but can present with symptoms related to mass effects such as headache , visual impairment , vomitings , features of panhypopituitarism and hypothalamic dysfunction . a 68-year - old indian male patient presented with the complaints of generalized malaise , poor appetite , weight loss , headache and polyuria for last 2 months . he had a chronic ill - looking appearance , a dehydrated tongue and dry skin . urine output was 5000 - 5500 ml / day with a history of nocturia and craving for cold fluids . no history of head injury , tubercular meningitis , central nervous system infections or chronic drug intake . his physical findings on admission were height 156 cm ; body weight , 44.5 kg and body mass index , 18.3 . blood pressure was 100/64 mmhg without postural change and pulse rate , 68/min with a regular rhythm . laboratory findings were as follows : white blood cell count 6400/mm ( neutrophils 51% , lymphocyte 42% , monocyte 5% , eosinophils 2% , basophils 0% ) ; hemoglobin , 13.4 g / dl ; hematocrit , 35.5% ; red blood cell count , 3.4 10/mm ; and platelets , 3.3 10/mm serum sodium was 137 mmol / l ; potassium , 3.9 mmol / l ; and chloride , 103 mmol / l . blood urea nitrogen was 12 mg / dl ; serum creatinine , 0.8 mg / dl ; and uric acid , 6.1 mg / dl . fasting plasma glucose was74 mg / dl ; hemoglobin a1c , 4.9% and serum calcium of 9.4 mg / dl . anterior pituitary function tests revealed panhypopituitarism ( serum cortisol 1.8 g / dl , adrenocorticotrophic hormone 15.6 pg / ml , total t3 56 ng / ml , total t4 4.2 g / dl , thyroid stimulating hormone 1.86 miu / ml , luteinizing hormone 0.8 miu / ml , follicle stimulating hormone 1.67 miu / ml , serum testosterone of 122 ng / dl and serum prolactin of 12 ng / ml . results of water deprivation test magnetic resonance imaging ( mri ) revealed [ figures 1 and 2 ] a well - defined sellar - suprasellar lesion , which was heterogenous and mildly hyperintense on t1-weighted images and brightly hyperintense on t2-weighted ( t2w ) images . magnetic resonance imaging pictures well - defined sellar - suprasellar heterogenous lesion and mildly hyperintense on t1-weighted ( t1w ) images and brightly hyperintense on t2-weighted ( t2w ) images suggestive of rathke 's cyst magnetic resonance imaging pictures well - defined sellar - suprasellar heterogenous lesion and mildly hyperintense on t1-weighted ( t1w ) images and brightly hyperintense on t2-weighted ( t2w ) images suggestive of rathke 's cyst transsphenoidal surgery with complete excision of the mass was carried out and histopathological examination revealed cyst wall with columnar lining suggestive of rcc . his symptoms improved and he was doing well in follow - up . surprisingly his polyuria improved in postsurgical period without vasopressin replacement . rcc arises from the remnants of rathke 's pouch , which is an invagination of the stomodeumand is formed by the fourth gestational week . rathke 's pouch is normally obliterated by the proliferation of the anterior and posteriorlobe of the pituitary gland , which forms a thin residual cleft in the gland . this cleft persists as a cyst lined with columnar or cuboidal epithelium of ectodermal origin . failure of obliteration with the proliferation of the lining cells with accumulation of secretions may result in cyst formation between anterior and middle lobes . rcc is usually asymptomatic and found in about 20% of normal pituitary glands in autopsy . the most common presenting symptoms are due to mass effect such as headache , visual disturbance . the mean age of presentation is 38 years with the highest frequency in the fifth decade and marked female preponderance . the most frequent cases involve hyperprolactinemia , followed by gonadotropindeficiency , pan - hypopituitarism , hypothyroidism and hypocortisolism . it is important to differentiate rcc from other neoplastic lesions , such as craniopharyngioma and pituitary adenoma . transsphenoidal surgery is preferred because there is a danger of damage to the hypothalamus and optic apparatus . surgical treatment is generally recommended even when patient has mild symptoms or signs , increased prolactinor a cyst size of more than 10 mm . in general , the prognosis after a partial removal of the cyst wall or simple aspiration of the cyst seems to be good even though the cyst recurs . patients with small - sized rcc or even asymptomatic , should be followed - up regularly with an mri .

rathke 's cleft cysts ( rcc ) are cystic sellar and suprasellar lesions derived from remnants of rathke 's pouch , lined by cuboidal or columnar epithelium . rcc are usually asymptomatic but can present with headache , visual impairment , panhypopituitarism and hypothalamic dysfunction . diabetes insipidus as a presenting symptom of rcc is reported , but rare . we present a case of a 48-year - old male presenting with polyuria and on investigations found to have central diabetes insipidus due to a sellar rcc . patient underwent transsphenoidal surgery with complete excision with resolution of his symptoms . his polyuria resolved post - surgery without vasopressin replacement , which has never been reported .

tangle functors have been central in the construction of quantum invariants of links and three - manifolds since reshetikhin and turaev s pioneering work @xcite . the starting data is a quasitriangular hopf algebra . this is a hopf algebra @xmath13 along with an invertible element @xmath14 of a completion of @xmath15 that satisfies three equations . if @xmath16 , let @xmath17 , @xmath18 and @xmath19 . the equations are @xmath20 where @xmath21 and @xmath22 are the comultiplication and the flipped comultiplication in @xmath13 , and @xmath23 and @xmath24 an element @xmath25 satisfying the above properties is called a * universal @xmath14-matrix*. these conditions imply that @xmath14 satisfies the quantum yang - baxter equation , @xmath26 and if @xmath27 denotes multiplication by @xmath14 followed by flipping the coordinates , then @xmath27 satisfies the standard braid relation , @xmath28 hence quasitriangular hopf algebras give rise to representations of the braid group . tangle functors are the extension of this representation to a representation of the category of framed colored tangles on the category of representations of the quasitriangular hopf algebra . the most important examples of quasitriangular hopf algebras are the drinfeld - jimbo deformations of the universal enveloping algebra of a semisimple lie algebra where the deformation parameter is a complex number that is not a root of unity @xcite . if there is a universal @xmath14-matrix , then the representations of the algebra commute under tensor product , that is if @xmath29 and @xmath30 are two representations of @xmath13 then @xmath31 is equivalent to @xmath32 . roots of unity need to be avoided because the representations of the algebra do not commute under tensor product . these noncommuting representations are sometimes called * cyclic * representations . the center of the deformed algebra has a subalgebra @xmath33 of finite index which is a hopf algebra . in fact , @xmath33 is the coordinate ring of the poisson dual of the lie group underlying the original lie algebra . the cyclic representations are associated with points of a branched cover of the dual lie group @xcite . the cyclic representations are used to construct * quantum hyperbolic invariants * of three manifolds . their restriction to the positive part of the quantum group play a role in kashaev s invariant@xcite , the quantum hyperbolic invariants of baseilhac and benedetti @xcite , and implicitly in the representation theory of the kauffman bracket skein algebra @xcite . [ uq]let @xmath34 be a complex number . the algebra @xmath3 is generated by @xmath35 , @xmath36 and @xmath37 with relations , @xmath38 the counit , antipode and comultiplication extend as , @xmath39 @xmath40 @xmath41 this is the version of @xmath3 appearing in @xcite , and @xcite . as @xmath3 is not quasitriangular at roots of unity , something must be done in order to get a tangle functor . in @xcite , they work with a quotient of @xmath3 where @xmath42 and @xmath43 . in this quotient , @xmath44 and @xmath45 . this algebra is quasitriangular , and the @xmath14 matrix is , @xmath46!}q^{\frac{l(l-1)}{2}}e^l\otimes f^l,\ ] ] where @xmath47 . ohtsuki realized that the requirement that @xmath44 was superfluous @xcite , and the same @xmath14-matrix defines a tangle functor based on the larger version of the quantum group . in this paper we find one more extension of the cases where a tangle functor can be constructed . here we assume that @xmath0 is a primitive @xmath1th root of unity where @xmath2 is odd and greater than or equal to @xmath48 . we need @xmath49 and @xmath50 to define a tangle functor . we can not work on the level of the algebra as even when we enforce the relations @xmath49 and @xmath50 in the algebra , there is no universal @xmath14-matrix . hence we work at the level of the representations . we call representations @xmath51 that satisfy @xmath11 and @xmath10 , * semicyclic*. first we prove that in these representations a solution to the quantum yang - baxter equation exists and is the image of the @xmath14-matrix in equation [ arr ] . next we prove that for @xmath12-tangles the tangle functor returns the same value as if we colored the tangle with the standard irreducible @xmath2-dimensional representation of @xmath3 . hitoshi murakami tells us that jun murakami already knew this . this does not mean that the functor contains no new information . the functor applied to @xmath52-tangles carries new information beyond the information in the functor coming from the standard @xmath2-dimensional representation . we would like to thank thomas kerler who shared with us his insight into a truly elegant proof that the tangle functor based on semicyclic representations returns the same answer as with the standard @xmath2-dimensional representation . given a @xmath12-tangle the functor returns a universal polynomial in @xmath53 with coefficients in @xmath54 , so that the exponential sum of @xmath36 is equal to the exponential sum of @xmath37 in every monomial appearing with nonzero coefficient . any such monomial can be written as a linear combination of polynomials in @xmath35 and the quantum casimir operator . the actions of these operators agree in the standard @xmath2-dimensional representation and the semicyclic representations . among other things , this means that it is impossible to get quantum hyperbolic invariants from a tangle functor that uses the standard @xmath14-matrix for @xmath3 . throughout this paper @xmath55 where @xmath56 is an odd counting number . the quantum integer @xmath57 , denoted @xmath58 $ ] is defined as , @xmath59=\frac{q^l - q^{-l}}{q - q^{-1}}.\ ] ] the quantum factorial is defined recursively by @xmath60!=1 $ ] , and @xmath61!=[n][n-1]!$ ] . the quantum binomial coefficients are defined by @xmath62=\frac{[n]!}{[k]![n - k]!}.\ ] ] the quantum binomial theorem states that if @xmath63 then , @xmath64 a^kb^{n - k}.\ ] ] the weyl algebra @xmath65 is a hopf algebra generated by @xmath36 , @xmath66 and @xmath6 with relation @xmath67 , antipode , @xmath68 , @xmath69 , counit given by @xmath70 , @xmath71 , and comultiplication @xmath72 and @xmath73 . let @xmath74 be the finite dimensional vector space over the complex numbers with basis @xmath75 where @xmath76 . choose a nonzero complex number @xmath77 . let @xmath78 denote @xmath79 matrices with complex coefficients , identified with @xmath80 via the choice of basis . define a representation of @xmath65 by , @xmath81 by @xmath82 , and @xmath83 when @xmath84 and @xmath85 . cyclic representations of the weyl algebra have been studied by kashaev @xcite , baseilhac and benedetti @xcite and bonahon et al @xcite . let @xmath3 denote the unreduced quantum group as in definition [ uq ] . we remind the reader though , that we are only considering the cases where @xmath86 where @xmath56 is an odd counting number . the following equations and proposition will be useful in showing that the @xmath14-matrix , defined in section [ sec : rmatrix ] , satisfies the quantum yang - baxter equation . by induction @xmath87f^{l-1}\frac{q^{1-l}k - q^{l-1}k^{-1}}{q - q^{-1}}.\ ] ] also @xmath88 where @xmath89 . [ prop : deltah ] @xmath90 the fact that @xmath72 forces @xmath91 . using induction , it can be shown that @xmath92 then , @xmath93 the cyclic representations of @xmath65 defined in section [ weyl ] can be extended to @xmath2 representations of @xmath3 as follows . let @xmath74 be the vector space over the complex numbers with basis @xmath94 where @xmath95 . fix @xmath96 and @xmath97 . let @xmath98 , and @xmath99 when @xmath84 and @xmath100 . notice that @xmath101 and @xmath102 where @xmath103 is the @xmath104 identity matrix . we find a representation @xmath105 of @xmath37 such that @xmath106 . under this condition , the equation @xmath107 leads to the following solution for @xmath108 . denote by @xmath109 the equivalence class of @xmath110 which we treat as the remainder on division by @xmath2 . define @xmath111v_{\overline{i+k-1 } } & : \overline{i+k } \ne \overline{0 } \\ & \\ \sum_{j=0}^{\overline{k-1 } } - \frac{[2(k - j)+n-1]}{a}v_{\overline{i+k-1 } } & : \overline{i+k } = \overline{0 } \end{array } \right.\ ] ] equivalently , @xmath108 can be expressed using the sum to product formula , @xmath112 [ n - k ] v_{\overline{i+k-1 } } & : \overline{i+k } \ne \overline{0 } \\ & \\ \frac{[k ] [ n - k]}{a}v_{\overline{i+k-1 } } & : \overline{i+k } = \overline{0 } \end{array } \right.\ ] ] the definition of these @xmath2 representations leads to the following relations . @xmath113 in fact , all @xmath2 of the representations are isomorphic via conjugation by @xmath114 . @xmath115 these representations are a subclass of those studied in @xcite and are called * semicyclic representations*. since there is only one semicyclic representation up to isomorphism , we will work with whichever is most convenient . one of the main goals of this paper is to compare the semicyclic and standard irreducible representations of @xmath3 . let @xmath116 denote the standard @xmath2-dimensional irreducible representation of @xmath3 . fix a basis @xmath117 of a vector space @xmath74 , then @xmath118 , and @xmath119 act on this basis as follows . @xmath120 for @xmath121 and @xmath122 , @xmath123[n - i ] v_{i-1}$ ] , @xmath124 . the standard representation , @xmath116 , is similar to the semicyclic representation @xmath125 . in fact , the only difference is @xmath122 while @xmath126 . in the case of the standard irreducible representation @xmath116 , the @xmath14-matrix @xmath127!}q^{\frac{l(l-1)}{2}}e^l\otimes f^l,\ ] ] satisfies @xmath128 where @xmath22 is the flipped comultiplication . this equation also holds for subrepresentations of tensor powers of the two dimensional irreducible representation . this formula first appeared in kirby and melvin @xcite , only they were working in the quotient of @xmath3 by @xmath129 , and @xmath130 . this formula for the @xmath14-matrix also appears in the work of ohtsuki where he notices that the condition @xmath130 is superfluous . it is also used in the unfolded version of the quantum group , where you add a generator @xmath13 with @xmath131 . in the following proposition we will show that the image of @xmath14 in the representations @xmath105 conjugates the image of comulitplication to the image of flipped comultiplication . [ prop : rdeltar ] for all @xmath132 , @xmath133 and @xmath134 , satisfies @xmath135 in the following proof , we suppress the notation @xmath105 and use @xmath136 and @xmath14 to mean their image under the representation @xmath105 . since @xmath50 the proof that @xmath137 and @xmath138 is the same as the proof appearing in @xcite . all that is left to show is @xmath139 . to simplify notation , write @xmath140 to prove the theorem we show that the equation @xmath141 holds for our choice of @xmath14 . using equation [ comult ] we get , @xmath142 using the commutation relations for @xmath143 from equation [ eq : qh ] , move it to the front of the second term and factor it out to get , @xmath144 cancel @xmath143 , distribute and then collect in powers of @xmath36 , to get , @xmath145 there is exactly one term with @xmath146 appearing in it , @xmath147 all other terms will cancel as in the proof in @xcite so we only need to show this term is zero . under all representations @xmath105 , @xmath37 has rank @xmath148 , so @xmath149 has rank @xmath150 . specifically @xmath151 spans the cokernel of @xmath149 , and its kernel is spanned by all other @xmath152 . applying @xmath153 to @xmath151 under @xmath105 gives @xmath154 now we can make a standard inductive computation of the @xmath14-matrix , noting that @xmath155 . going back to equation [ eqn ] , commute the @xmath36 past @xmath156 in the second term , and @xmath6 past @xmath157 in the first , and renumber the first term so that @xmath158 become @xmath159 . we get , @xmath160f^{m-1}\frac{q^{1-m}k - q^{m-1}k^{-1}}{q - q^{-1}})=0.\ ] ] collecting in powers of @xmath36 we get the recursive formula , @xmath161}q^{m-1}c_{m-1}.\ ] ] setting @xmath162 we get the standard formula for the @xmath14-matrix given above . recall , a universal @xmath14-matrix satisfies @xmath163 , and @xmath164 . the first of these two equations holds in semicyclic representations because it is true when @xmath165 , and @xmath50 suffices . this is because the only powers of @xmath36 and @xmath37 in the formula that exceed @xmath148 are in fact powers of @xmath37 , for instance see @xcite for the proof . the second equation does not hold in the semicyclic representations . to see why , apply proposition [ prop : deltah ] to the left hand side @xmath166 . @xmath167 notice that the highest power of @xmath36 or @xmath37 that appears is @xmath148 . since the equation is true when @xmath129 in the algebra it means that the coefficients of @xmath168 all monomials where the powers of @xmath36 and @xmath37 are less than or equal to @xmath148 agree with the answer above . for the right hand side , we have @xmath169 commuting @xmath170 to the front yields , @xmath171 now cancel the exponentiated @xmath172 from both sides . we know that all the terms where @xmath173 cancel with the left hand side so the remainder is , @xmath174 the matrices @xmath175 where @xmath176 ranges from @xmath2 to @xmath177 are linearly independent . hence each of the parts of the sum where @xmath178 needs to be zero . letting @xmath179 we get , @xmath180 consider @xmath181 . the values of this vector under each term of the sum are linearly independent , so the sum is nonzero and the relation @xmath164 does not hold under the semicyclic representations . however , the @xmath14-matrix still satisfies the yang - baxter equation , as long as we are evaluating in the representations @xmath105 . let @xmath182 be the flip @xmath183 . let @xmath184 denote its extension @xmath185 . if @xmath186 then @xmath187 suppose @xmath188 is any of the semicyclic representations of @xmath3 . then @xmath189 the proof follows @xcite . it really only depends on the fact that if we evaluate in @xmath190 , where @xmath191 is an arbitrary representation , and @xmath192 is a semicyclic representation where the kernel of @xmath37 contains @xmath75 , then @xmath193 and @xmath194 when in addition @xmath195 is semicyclic . to simplify notation we suppress the representation from the formulas . in this section , we define a tangle functor for @xmath12-tangles that have been colored with the extended semicyclic representations defined in section [ sec : extending ] . let @xmath198 be a basis for an @xmath2-dimensional vector space @xmath74 over @xmath199 . for @xmath200 and @xmath201 define the cup , cap , and crossing operators as follows . [ cols= " < , < " , ] * remark * : in the last step , the exponent of @xmath0 , @xmath202 is replaced with @xmath203 . this is due to the linear relations @xmath204 and @xmath205 coming from the caps . this will be the case for every knot . later we will show that this invariant is the same as kashaev s invariant so we do not find a closed form for the final solution . given a @xmath12-tangle @xmath66 we denote the invariant of @xmath66 coming from the semicyclic representations with @xmath206 by @xmath207 coming from the irreducible semicyclic representations is shown to recover kashaev s invariant . specifically , we show that @xmath207 evaluated at a @xmath208 root of unity is equivalent to kashaev s invariant evaluated at a @xmath208 root of unity for any knot . a word @xmath209 is said to be * balanced * if @xmath210 . in the prior section , @xmath207 was calculated for the figure eight knot . that calculation shows that @xmath207 for any knot will be a sum of balanced words in @xmath36 and @xmath37 with coefficient functions of @xmath0 to a power . the proof will be by induction on the length of a word @xmath219 where the total degree of @xmath36 and @xmath37 are equal . for the base case , consider the word @xmath220 of length 2 . for a fixed integer @xmath2 where @xmath221 , the center of @xmath3 is generated by the standard quadratic casimir defined by @xmath241 . if the casimir is evaluated at the standard irreducible representation , @xmath116 , of @xmath3 then it will clearly not involve any @xmath240 since @xmath242 . the prior proposition shows that the casimir will not involve any @xmath240 when evaluated at the semicyclic irreducible representations discussed in this paper . [ prop : casimir ] let @xmath209 be a balanced word in @xmath36 and @xmath37 , then @xmath219 can be written as a product of the terms @xmath243_q)$ ] where @xmath244_q = \frac{q^rk - q^{-r}k^{-1}}{(q - q^{-1})^2}$ ] and @xmath245 . by induction and using the formula for the casimir , it can be shown that @xmath249_{q^{-1}})$ ] and @xmath250_{q})$ ] . with this in hand , the same induction argument from proposition [ prop : noa ] will show that any balanced word can be written in terms of the casimir and @xmath251_q$ ] . in this proof , we choose to use @xmath125 when calculating @xmath207 . kashaev s invariant is calculated in the same way as @xmath207 except evaluated at the standard irreducible representation @xmath116 . by definition , we have @xmath253 . therefore , the cup and cap operators are identical under either representation . also , @xmath254 acts the same under either representation . by proposition [ prop : casimir ] , we can complete the proof by checking that @xmath255 or @xmath256 evaluates the same under both representations . notice that @xmath257 and the only difference between @xmath258 and @xmath259 is their action on the basis vector @xmath260 . thus we only need to check the action of @xmath256 on @xmath260 under each representation . but , under both representations @xmath261 . 0000 baseilhac , stephane _ quantum coadjoint action and the @xmath262-symbols of @xmath263._interactions between hyperbolic geometry , quantum topology and number theory , 103143 , contemp . , * 541 * , amer . math . soc . , providence , ri , 2011 . baseilhac , stephane ; benedetti , riccardo _ quantum hyperbolic geometry _ , algebr . geom . topol.*7 * ( 2007 ) , 845917 . bonahon , francis ; liu , xiaobo _ representations of the quantum teichmller space and invariants of surface diffeomorphisms _ , geom . * 11 * ( 2007 ) , 889937 . fok , v. v. ; chekhov , l. o. _ quantum teichmller spaces _ , ( russian ) teoret . mat . * 120 * ( 1999 ) , no . 3 , 511528 ; translation in theoret . and math . phys . * 120 * ( 1999 ) , no . 3 , 12451259 de concini , c. ; procesi , c. _ quantum groups _ d - modules , representation theory , and quantum groups ( venice , 1992 ) , 31140 , lecture notes in math . , * 1565 * , springer , berlin , 1993 . geer , nathan ; patureau - mirand , bertrand _ g - links invariants , markov traces and the semicyclic @xmath264-modules _ , j. knot theory ramifications * 22 * ( 2013 ) , no . 11 , 1350063 , 28 pp . kassel , christian _ quantum groups _ graduate texts in mathematics , * 155 * springer - verlag , new york , 1995 . xii+531 pp . isbn : 0 - 387 - 94370 - 6 . kashaev , r. m. _ quantization of teichmller spaces and the quantum dilogarithm _ , lett . phys . * 43 * ( 1998 ) , no . 2 , 105115 . kashaev , r. m. _ quantum dilogarithm as a 6j - symbol _ , modern phys . a * 9 * ( 1994 ) , no . 40 , 37573768 . kirby , robion ; melvin , paul _ the 3-manifold invariants of witten and reshetikhin - turaev for sl(2,c ) _ , invent . math . * 105 * ( 1991 ) , no . 3 , 473545 . ohtsuki , tomotada quantum invariants . a study of knots , 3-manifolds , and their sets . series on knots and everything , 29 . world scientific publishing co. , inc . , river edge , nj , 2002 . xiv+489 pp . isbn : 981 - 02 - 4675 - 7 . reshetikhin , n. _ quasitriangularity of quantum groups at roots of @xmath150 _ comm . * 170 * ( 1995 ) , no . 1 , 7999 . kashaev , rinat ; reshetikhin , nicolai _ braiding for quantum @xmath265at roots of unity _ noncommutative geometry and representation theory in mathematical physics , 183197 , contemp . math . , * 391 * , amer . soc . , providence , ri , 2005 . reshetikhin , n. yu . ; turaev , v. g._ribbon graphs and their invariants derived from quantum groups _ comm . phys.*127 * ( 1990 ) , no . 1 , 126 . reshetikhin , n. ; turaev , v. g. _ invariants of 3-manifolds via link polynomials and quantum groups _ invent . math . * 103 * ( 1991 ) , no . 3 , 547597 . turaev , v. g. _ quantum invariants of knots and 3-manifolds _ , de gruyter studies in mathematics , 18 . walter de gruyter & co. , berlin , 1994 . isbn : 3 - 11 - 013704 - 6

let @xmath0 be a @xmath1th root of unity where @xmath2 is odd . let @xmath3 denote the quantum group with large center corresponding to the lie algebra @xmath4 with generators @xmath5 , and @xmath6 . a semicyclic representation of @xmath3 is an @xmath2-dimensional irreducible representation @xmath7 , so that @xmath8 with @xmath9 , @xmath10 and @xmath11 . we construct a tangle functor for framed homogeneous tangles colored with semicyclic representations , and prove that for @xmath12-tangles coming from knots , the invariant defined by the tangle functor coincides with kashaev s invariant .

the key feature of copper oxides is the layered structure and led to speculation that reduced dimensionality is a necessary prerequisite for superconductivity at temperatures above @xmath7 @xcite . although two dimensional ( @xmath8 ) models , such as @xmath1-@xmath2 model or hubbard model , have captured essential of superconductivity , and successfully explained properties of the un - doped insulator and occurrence of gap in superconductors , @xmath8 models alone can not describe and explain all observations of experiments @xcite . despite how large the ratio between out - of - plane and in - plane resistivity is , at the phase transition temperature @xmath9 , both resistivities drop to zero simultaneously , this indicates the phase transition is of three dimensional @xcite , meanwhile , the observed antiferromagnetism is definitely a @xmath10 phenomenon @xcite . some works provided evidence that superconductivity in the infinite - layer compounds @xmath11 @xcite is of three - dimensional nature which do not contain a charge - reservoir block and the distance from one unit cell to the next is the shortest among all the cuprates . experimental data @xcite shows that the decrease of doping concentration is accompanied by a raise of anisotropy which is defined as the ratio of the correlation lengths parallel and perpendicular to the @xmath12 plane in cuprates superconductivity . for materials @xmath13 , @xmath14 @xcite and @xmath15 @xcite , coherence length and the anisotropy ratio imply that they are anisotropic @xmath10 superconductors , these phenomena are supported by good @xmath10 scaling analysis @xcite . recently observed @xcite superconductivity in iron - arsenic - based compounds has attracted many attention . our motivation of investigating three dimensional isotropic superconductivity come directly from the measurements of the electrical resistivity in single crystals of @xmath0 in a magnetic field up to @xmath16 @xcite , yuan _ et al _ found that the superconducting properties are in fact quite isotropic , appear more three dimensional than that of the copper oxides . their results indicates that reduced dimensionality in these compounds is not necessarily a prerequisite for high temperature superconductivity . @xmath10 anisotropic @xmath1-@xmath2 model has already been studied before @xcite . by using mean - field hamiltonian and carrying out expansion of free - energy , two main results were obtained @xcite : one is that transition temperature decreases weakly with both increasing of @xmath10 coupling strength and doping concentration , the other one is that in all cases @xmath5-wave pairing ansatz has the lowest energy . however , in simple cubic lattice ( scl ) , each site has six nearest neighbors(nn ) settled in three perpendicular directions , no direction is special , if superconducting behavior is possible , its symmetry can not be conventional @xmath5-wave . with the help of renormalized mean - field theory@xcite(rmft ) , we found that for isotropic case , pairing parameters on the three perpendicular directions have @xmath4 phase shift to each other . while as interaction in @xmath3 direction is suppressed , corresponding amplitude of pairing parameter drops quickly from infinite value to zero . by tuning coupling integral in @xmath3 direction , our calculation shows that superconducting symmetry are functions of the anisotropic parameter and doping concentration . moreover , as the anisotropic parameter decreases from @xmath17 to @xmath6 , symmetry of pairing parameters change from @xmath4 of @xmath10 to @xmath5-wave of @xmath18 . this may give some understanding of @xmath10-@xmath18 crossover . in scl , anisotropic @xmath1-@xmath2 model can be written as @xmath19 with @xmath20 where @xmath21 is the gutzwiller projection operator @xcite which removes totally the doubly occupied states , @xmath1 and @xmath2 are the electron hoping interaction and antiferromagnetic exchange interaction , respectively . @xmath22 is to create an electron with spin @xmath23 at site @xmath24 , and @xmath25 is a spin operator . summation @xmath26 runs over all nn in @xmath27 plane , while summation @xmath28 runs over all nn in direction @xmath3 which is perpendicular to @xmath27 plane . for convenience , all anisotropic parameters are put into @xmath3 direction terms , @xmath29 and @xmath30 are anisotropic parameters with range @xmath31 $ ] , @xmath32 corresponding to the isotropic case . in rmft the wavefunction of the hamiltonian is assumed to be the projected state @xmath33 , @xmath34 , where @xmath35 is constrained in the reduced brillouin zone , and the two coefficients satisfy @xmath36 . the projection operator can be taken into account by a set of renormalized factors @xcite defined as @xmath37 , @xmath38 , where @xmath39 denotes expectation value of unprojected state @xmath40 , and @xmath41 denotes expectation value of physical state @xmath42 . then one has @xmath43 . in homogenous case the renormalized factors @xcite take the form of @xmath44 and @xmath45 . considering even - parity case in which @xmath46 and @xmath47 , the expectation value of the effective hamiltonian has the same form as that of @xmath18 @xmath48 where @xmath49 is the total number of sites and @xmath50 in order to investigate superconducting property , one should introduce two mean - field parameters such as particle - particle(pairing ) parameter @xmath51 and particle - hole parameters @xmath52 . by minimizing the quantity @xmath53 with respect to @xmath54 and @xmath55 , where @xmath56 is denoted as chemical potential , one gets the coupled gap equations @xmath57 where @xmath58 indicates the three perpendicular directions @xmath59 , @xmath60 , @xmath61 , @xmath62 , @xmath63 , and @xmath64 . these gap equations should be solved simultaneously with doping concentration @xmath65 . after iterative self - consistent solving , for a set of given @xmath66 , @xmath29 , @xmath30 and @xmath67 one can obtain all those particle - particle and particle - hole parameters simultaneously . superconductivity symmetry is determined by the phase shift of different pairing parameters @xmath68 and the superconductivity parameter @xmath69 @xcite equals @xmath70 . parameters amplitude as functions of doping concentration @xmath66 . @xmath71 denotes amplitude of particle - hole parameter , @xmath72 denotes pairing parameter , and @xmath73 is superconducting parameter defined as @xmath74.,width=302 ] for isotropic scl , @xmath75 . in half - filled case , @xmath76 , @xmath77 , there is a trivial solution with @xmath78 corresponding to projected fermi - liquid . @xmath79 changes its sign at the surface and the average energy of per site is @xmath80 . for non - trivial solution , by using eq.([h ] ) , the energy per site can be written as @xmath81 , here relations @xmath82 and @xmath83 have been used . by assuming @xmath84 and substituting it into gap equations , one can get @xmath85 and the energy of per site is @xmath86 , which is lower than the energy of the projected fermi liquid state and is more favored and stable . in the non - trivial case parameters should satisfy following equations simultaneously @xmath87 it has @xmath88 degeneracy , the most important solution is @xmath89 it clearly shows that the phase shift of different @xmath68 is @xmath90 . by changing the sign of @xmath91 and taking the phase difference of any two pairing parameters as @xmath92 , one can obtain another solution and if one sets one or two of the three @xmath93 as zero other solutions can also be obtained . all these solutions have the same energy . among these energetically degenerated states the @xmath4 symmetric state has the best kinetic energy @xmath94 . upon doping degeneracy will be lifted , superconducting state favors the best kinetic energy state , which is the @xmath90 symmetry state . this is also the reason why we call this solution as the most important one . hoping integral @xmath1 is used as energy unit , and @xmath95 is taking in order to be consistent with the superexchange relation of @xmath96 in the large hubbard @xmath97 limit . for isotropic @xmath98 case , self - consistent parameters as functions of doping concentration are shown in fig.[1 ] . amplitude of all @xmath68 are the same which is denoted as @xmath99 in the figure . every @xmath100 is real and has the same value of @xmath93 . one can see from fig.[1 ] that with doping increasing , amplitude of pairing parameters decreases , while superconducting parameter @xmath101 varies along a non - monotonic curve . these properties are similar to that of @xmath18 square lattice . the most interesting result is that each @xmath68 has imaginary part , @xmath102 is used to denote phase of @xmath68 , the pairing parameters have @xmath4 phase shift to each other just as that of half - filled case . for @xmath103 . right picture shows how the phases @xmath102 varied as function of @xmath66.,width=302 ] when the interaction in @xmath3 direction is suppressed , amplitude of the corresponding parameters will deviate from those of @xmath27 plane . in order to make the situation more simpler , we set @xmath104 . for @xmath105 , the doping dependent parameters are presented in fig . [ 2 ] . [ 2](a ) shows that @xmath30 affects amplitudes of both paring parameter and particle - hole parameter , with increasing @xmath66 all pairing parameters decrease with @xmath106 . anisotropy also affects the symmetry of the @xmath68 . [ 2](b ) demonstrates that at half - filled point @xmath107 , and @xmath108 decreases with increasing @xmath66 . accompanied by decrease of @xmath109 , @xmath108 approaches to @xmath110 . for @xmath111 , as shown in fig . [ 3](a ) with @xmath66 increasing @xmath109 drops more rapidly than @xmath112 and vanishes at @xmath113 . symmetry of pairing parameters are shown in fig.[3](b ) , @xmath108 decreases from about @xmath114 to @xmath110 at @xmath113 . for @xmath115 , system apparently behaves as @xmath18 with superconducting order being @xmath116 symmetry . by compare above two anisotropic cases one can reasonably expect that at a given anisotropic parameter , system will behave as @xmath18 in all doping level . for @xmath117 . right picture shows how the phases @xmath102 varied as function of @xmath66.,width=302 ] this property can be demonstrated clearly in half - filled case . for anisotropic half - filling , @xmath118 where @xmath119 , @xmath120 , @xmath24 represents @xmath121 or @xmath122 direction . for a given @xmath30 one can obtain the phase difference @xmath108 and the value of @xmath123 for the best kinetic energy state . as @xmath124 , it reduces to the isotropic case . as @xmath125 approaches to @xmath126 , degree of anisotropy is very large and the system turns to a quasi-@xmath18 one . from fig . [ 4 ] one can see that by decreasing @xmath30 from @xmath17 , @xmath127 decreases quickly and reaches zero at about @xmath128 , simutanously the phase difference @xmath108 increases from @xmath4 to @xmath110 . these results indicate that as the anisotropic parameter decreases to @xmath6 , @xmath129 vanishes , and system loses its @xmath10 character . decreasing , amplitude of @xmath130 drops quickly . phase difference @xmath108 as function of anisotropic coefficient is presented in right picture . , width=302 ] experiment shows that @xmath131-type ternary iron arsenides possess three - dimension properties @xcite , although the microscopic nature of superconductivity in iron - based compound is not clearly at present , and one band model is not enough to describe them , we investigated isotropic and anisotropic @xmath1-@xmath2 model on simple cubic lattice to show the superconductivity symmetry from mean - field point of view . for isotropic three - dimensional @xmath1-@xmath2 model , superconductivity ground state is not conventional @xmath5-wave , phase shift of each pairing parameter is exactly @xmath4 . for anisotropic cases three - dimensional character is not so obviously , adding a small anisotropic interaction on @xmath3 direction will induces a great anisotropy in its corresponding mean - field paring parameter and raise serious instability of previous @xmath10 superconducting symmetry . we found that pairing parameter @xmath129 depends strongly on the anisotropic parameter , as anisotropic parameter decrease to @xmath6 , system appears @xmath18 behavior . from this discussion one can see that @xmath10 character superconductor is sensitive to amplitude of couplings . the authors acknowledges professor fu - chun zhang for helpful discussions during the research work . this work is supported by nsf of china no.10747145 , no.10874149 and by shanghai leading academic discipline project no . s30105 . n. yamada , m. ido , physica c * 203 * ( 1992 ) * 240*. t. nagano _ et al_. , phys . b * 48 * ( 1993 ) * 9689*. y. fukuzumi _ et al_. , phys . rev . lett . * 76 * ( 1996 ) * 684*. t. sasagawaet _ et al_. , phys . b * 61 * ( 2000 ) * 1610*.

motivated by the finding of nearly isotropic superconductivity in @xmath0 , we use renormalized mean field theory to investigated the @xmath1-@xmath2 model on three - dimensional simple cubic lattice . a tunable anisotropic parameter is introduced to dictate the coupling on @xmath3 direction . the symmetry of the superconducting order is studied in detail . calculation shows that for the isotropic case , pairing parameters on the three perpendicular directions have @xmath4 phase shift to each other . however , when the interaction on @xmath3 direction is suppressed , the corresponding amplitude of the pairing parameter decreases rapidly , furthermore , two - dimensional @xmath5-wave state pairing is favored when the anisotropic rate less than @xmath6 .

in spin systems with a ground singlet state and excited triplet state the energy gap between the singlet and the triplet can be tuned with an external magnetic field . in srcu@xmath0(bo@xmath1)@xmath0 it was discovered that in magnetic fields above 22 t , where the spin gap is expected to close , several magnetization plateaus appear.@xcite at magnetization plateaus the triplets form a pattern which breaks the translational symmetry of the crystal structure.@xcite the heavy mass of the triplet excitations arising from an almost flat dispersion of energy on momentum@xcite favors the build - up of magnetic superstructures . below the critical field srcu@xmath0(bo@xmath1)@xmath0 has a ground state described first by shastry and sutherland.@xcite srcu@xmath0(bo@xmath1)@xmath0 consists of planes of cubo@xmath1 and sr atoms between the planes . cu@xmath8 spins ( s=1/2 ) form cu - cu dimers arranged into orthogonal dimer network . srcu@xmath0(bo@xmath1)@xmath0 is an experimental realization of a shastry - sutherland model.@xcite in the model there is an anti - ferromagnetic intra - dimer exchange coupling @xmath9 and inter - dimer coupling @xmath10 between spins on the nearest - neighbor dimers ( fig.[model2dimersstaticw ] ) . in the limit of @xmath11 the problem reduces to that of isolated dimers where the ground state is the product of singlet states and the first excited triplet state is at energy @xmath12 above the ground state , where @xmath13 is the energy per dimer . shastry and sutherland showed that for @xmath14 singlets on all dimers is an exact ground state too . the exactness of the ground state and the heavy mass of triplet excitations is the consequence of frustration originating from the special geometry of the dimer lattice in the shastry - sutherland model where the bonds on neighboring dimers are orthogonal . later on it has been shown that singlets on all dimers is the exact ground state for a larger range of @xmath15 up to the quantum critical point @xmath16 . at the quantum critical point the spin gap vanishes and a long - range anti - ferromagnetic order is established . different theoretical approaches have been used to calculate @xmath17 ( see ref.@xcite for review ) . it is possible that between the exact singlet ground state and the anti - ferromagnetic state in certain range of @xmath15 other gapped spin states exist.@xcite the singlet - triplet gap in srcu@xmath0(bo@xmath1)@xmath0 , @xmath18@xmath2 , has been measured directly by several experimental techniques : inelastic neutron scattering@xcite , electron spin resonance@xcite ( esr ) , raman scattering@xcite , and far - infrared ( fir ) spectroscopy.@xcite additional information besides @xmath13 is needed to determine the exchange parameters of srcu@xmath0(bo@xmath1)@xmath0 . the dispersion of the triplet excitation is not informative because of its flatness@xcite , but positions of other excited states or the temperature dependence of thermodynamic parameters can be used for determining the exchange parameters . miyahara and ueda@xcite found @xmath19@xmath2 and @xmath20 . they added an interlayer coupling @xmath21 to the model to obtain a better fit of the magnetization @xmath22-dependence above the critical temperature @xmath23 . based on the analysis of excitation spectra@xcite @xmath24@xmath2 and @xmath25 were proposed . such scattering of parameters could be either due to the incomplete model or due to the approximations made in theoretical calculations . srcu@xmath0(bo@xmath1)@xmath0 is near to the quantum critical point @xmath17 where the energy levels of the spin system are sensitive to the choice of @xmath9 and @xmath15 . a singlet level in the spin gap at 21@xmath2 found in the esr spectra@xcite may help to find proper parameters for the model . interactions other than inter- and intra - dimer exchange coupling can spoil the exactness of the ground state . this is important in high magnetic fields where the triplet state becomes degenerate with the ground singlet state . at this critical field even a weak interaction between the singlet and the triplet state mixes the two states completely . the singlet and triplet state anti - crossing effects were seen in the high field esr experiments.@xcite a possible anti - symmetric interaction which couples the singlet and the triplet states is the dm interaction . an intra - dimer dm is allowed by symmetry but its strength is not known below room temperature . above room temperature @xmath26@xmath2 has been estimated from the esr linewidth.@xcite the inter - dimer dm interaction , @xmath27@xmath2 , perpendicular to the dimer planes@xcite partially lifts the degeneracy of the triplet state but does not couple the triplet state to the singlet state . the effect of dm interactions on the magnetic dipole active esr transitions in srcu@xmath0(bo@xmath1)@xmath0 was investigated theoretically in ref.@xcite . lattice distortions , static or dynamic , are important in srcu@xmath0(bo@xmath1)@xmath0 since they lower the crystal symmetry and allow magnetic interactions which are otherwise forbidden in a more symmetric environment . srcu@xmath0(bo@xmath1)@xmath0 has a structural phase transition at 395k@xcite that induces a buckling of cubo@xmath1 planes in the low @xmath22 phase . as the phase transition point is approached from below the raman - active 62@xmath2 optical phonon mode softens.@xcite acoustic phonon modes have spin - phonon coupling at magnetization plateaus.@xcite it has been proposed that a spin superstructure at 1/8 plateau observed by nuclear magnetic resonance at 35mk is stabilized by a lattice distortion.@xcite instantaneous breaking of lattice symmetry by an optical phonon allows electric dipole active singlet - triplet transitions@xcite that explains fir polarized absorption spectra in srcu@xmath0(bo@xmath1)@xmath0.@xcite our aim is to find out which additional interactions are required to the shastry - sutherland model that add triplet corrections to the ground state . for that we do fir absorption measurements with polarized light in magnetic field and compare the absorption line frequencies and intensities with values calculated with a two dimer model including the dynamic dm effect . the important information is in the polarization and magnetic field dependence of the fir absorption lines and in the avoided crossing effects . we studied single crystals of srcu@xmath0(bo@xmath1)@xmath0 , ref.@xcite . the first sample consisted of two pieces 0.65 mm thick in a - direction with the total area of 12mm@xmath28 in the @xmath29 plane . the second sample was 0.6 mm thick in the c - direction and had an area of 11.5mm@xmath28 in the @xmath5 plane . the experimental details are described in ref . l|d|d|lldddd & & & & & & & + label & _ 1 & _ 1 & @xmath30 & @xmath31 & & g_a & g_c + & & & & & & + @xmath32 & a & c & @xmath33 & 21.50 & 0.03 & & + @xmath34 & a , c & c , a & @xmath35 & 22.72 & 0.05 & 1.988 & 2.219 + @xmath36 & a , c & c , a & @xmath35 & 24.11 & 0.05 & & + @xmath37 & a , c & c , a & @xmath35 & 25.51 & 0.05 & 1.988 & 2.219 + @xmath38 & a , c & c , a & @xmath33 & 28.57 & 0.03 & & + @xmath39 & c & a & 0.3 @xmath40 0.2 & 37.49 & 0.03 & 1.996 & 2.264 + @xmath39 & a & b , c & 0.9 @xmath40 0.2 & 37.51 & 0.04 & 2.001 & 2.23 + @xmath41 & a & c & 0.9 @xmath40 0.2 & 37.69 & 0.09 & & + @xmath42 & a & c & @xmath33 & 38.74 & 0.03 & 2.026 & + @xmath43 & c & a & @xmath33 & 38.70 & 0.15 & & + @xmath44 & c & a & @xmath33 & 39.08 & 0.15 & 2.067 & 2.29 + @xmath45 & a & c & 0.19 @xmath40 0.05 & 39.71 & 0.04 & & + @xmath46 & a & c & @xmath33 & 40.45 & 0.03 & 1.97 & + @xmath47 & c & a & 0.2 @xmath40 0.1 & 40.67 & 0.03 & & 2.243 + @xmath48 & a , c & c , a & 0.2 @xmath40 0.1 & 40.70 & 0.16 & & + @xmath49 & c & a & 0.4 @xmath40 0.1 & 41.11 & 0.13 & 2.10 & + @xmath50 & a & c & 0.2 @xmath40 0.1 & 42.7 & 0.2 & & 2.25 + @xmath51 & a & b , c & 2.6 @xmath40 0.3 & 43.00 & 0.16 & & + @xmath52 & c & a & 0.2 @xmath40 0.1 & 43.54 & 0.03 & & 2.31 + @xmath53 & c & a & @xmath33 & 44.7 & 0.4 & & + @xmath54 & c & a & @xmath33 & 47.04 & 0.04 & & + @xmath55 & c & a & 0.04 @xmath40 0.02 & 48.21 & 0.09 & & 2.27 + @xmath56 & a & b , c & 86 @xmath40 14 & 52.24 & 0.08 & & + @xmath57 & a & b , c & 24 @xmath40 3 & 53.44 & 0.07 & & as the result of the polarization sensitive measurement of fir spectra we have identified that the main resonances in the spectra are electric dipole transitions , rather than being magnetic dipole transitions . in fig . [ eaec4k4spec ] differential absorption spectra at 4.4 k relative to 15 k , are displayed . the strong absorption lines at 52.3 and 53.5@xmath2 were identified@xcite as electric dipole transitions , that are active in @xmath58 polarization . we see the same for the 43.0@xmath2 singlet and @xmath59 and @xmath60 triplets ( see table[alllines ] ) at 24.2 and 37.5 @xmath2 , respectively , which are present in the spectra measured with @xmath58 regardless of @xmath61 being perpendicular to the @xmath4 axis or parallel to it . the lines are missing in @xmath62 polarization@xcite , instead a new line appears at 25.5@xmath2 , which is identified as another component of the triplet @xmath59 . the triplets are split by the magnetic field @xmath63 . differential absorption spectra in @xmath64 polarization for one magnetic field direction , @xmath65 , measured relative to the zero field , are displayed in fig . [ baeaspec ] . we see an anti - crossing of the @xmath66 level with the singlet @xmath67 at 21.5 @xmath2 and an anti - crossing of the @xmath68 level with the singlet @xmath38 at 28.6 @xmath2 . all the peaks in the measured spectra in different light polarizations and @xmath63 directions were fitted with lorentzians . the results are summarized in table[alllines ] and displayed in figures [ baceclevelsprobab ] , [ eparaeigenprob ] , and [ eabbyeigenprob ] . the states above 38@xmath2 are labelled by their zero field frequencies . the magnetic field independent energy levels are labelled as singlets with the exception of those in the middle of the triplet levels @xmath69 . the hamiltonian for a spin pair with exchange coupling @xmath70 and dm interaction @xmath71 on the bond connecting spins @xmath72 and @xmath73 reads : @xmath74 + g\mu _ b \mathbf{b}_0 \cdot ( \mathbf{s}_k + \mathbf{s}_l ) . \label{pair_static}\end{aligned}\ ] ] here we included shekhtman corrections@xcite which are quadratic in @xmath71 ( see also@xcite ) . the last term is the zeeman energy of spins in the magnetic field @xmath63 where @xmath75 is the electron spin g - factor and @xmath76 is the bohr magneton . the formalism to introduce the spin - phonon coupling is similar to one used in ref.@xcite . we are interested in singlet to triplet transitions . therefore the relevant term is the anti - symmetric dm interaction @xmath77 $ ] which couples the singlet to the triplet state . we expand the dm vector @xmath78 into a power series of the lattice normal coordinate @xmath79 @xmath80 where @xmath81 is the static dm interaction in ( [ pair_static ] ) . we keep terms linear in @xmath79 . the full hamiltonian for a spin pair including the phonons is @xmath82 , \label{dynamic0order}\ ] ] where @xmath83 . the lattice normal coordinate @xmath84 is presented in terms of phonon creation and annihilation operators @xmath85 and @xmath3 , @xmath86 , where @xmath87 is the transformation coefficient and @xmath88 is the phonon frequency . the spin - phonon coupling term in ( [ dynamic0order ] ) is linear in @xmath85 and @xmath3 . therefore the phonon states with the occupation numbers @xmath89 and @xmath90 are coupled where @xmath91 . we will consider only two phonon states @xmath92 and @xmath93 , which is justified when @xmath94 . the normal coordinate @xmath79 in the dynamic dm singlet to triplet optical transition mechanism belongs to an optical phonon . electric dipole coupling between a phonon and light in the long wavelength limit is @xmath95 where @xmath96 is the effective charge associated with the lattice normal coordinate @xmath79 . here we assumed @xmath97 and dropped the time dependence of @xmath98 . once the eigenstates of ( [ dynamic0order ] ) are known the optical transition probability between the ground state @xmath99 and the excited state @xmath100 is calculated as @xmath101 . to calculate optical transitions in srcu@xmath0(bo@xmath1)@xmath0 we use a two dimer model depicted in fig.[model2dimersstaticw ] . in this model intra - dimer and inter - dimer superexchange interactions @xmath9 and @xmath10 are considered . the inter - dimer static dm vector @xmath102 is along the @xmath4 axis and alternates from bond to bond . the intra - dimer static dm vector @xmath103 exists due to the buckling of cu - o - b planes.@xcite the direction of dm vectors is defined by the right hand rule where the path is along the cu - o - cu bond ( for @xmath102 cu - o - b - o - cu ) in the direction of increasing spin index @xmath72 . in the vector product @xmath104 the spin with a smaller index is on the left , @xmath105 . when a periodic boundary condition is applied to the two dimer cluster , bounded by a box drawn with a thin dashed line in fig.[model2dimersstaticw](a ) , an effective spin model is obtained where the inter - dimer interactions are doubled , fig.[model2dimersstaticw](b ) . the doubling is necessary to conserve the number of next - nearest - neighbor bonds , which is four . the hamiltonian for the two dimer cluster is the sum of pairwise interactions ( [ dynamic0order ] ) where the sum runs over all the bonds in the cluster . we will use a basis @xmath106 where @xmath107 runs over the singlet @xmath108 and three triplet components @xmath109 , and @xmath110 on the @xmath9 bond of the dimer @xmath111 and @xmath112 over the singlet and triplet states of the dimer @xmath113 . @xmath89 is the number of phonons , 0 or 1 . the basis has 32 components . below we consider @xmath3- and @xmath4-axis phonons , shown in fig.[model2dimersdynamic ] , named by the direction of their electric dipole moment . the effect of the dynamic dm interaction on the position of energy levels is small because we take @xmath114@xmath2 that is substantially larger than the singlet - triplet gap . we use this value since there are no optical phonons with substantial spectral weight below 100@xmath2 as our transmission measurements show . the energy spectrum can be analyzed separately from the dynamic dm effect because of the high phonon energy . the calculated energy levels are the same in fig.[baceclevelsprobab ] and [ eparaeigenprob ] . in these figures only the zero phonon levels of the triplet @xmath59 and @xmath38 are shown . the levels with one excited phonon are off - set by @xmath115 to higher energies and are not shown . in a two dimer system two singlets , two triplets , and a quintet are present . the ground state is a product of singlets @xmath116 . the first triplet is a linear combination of @xmath117 and @xmath118 . in the two dimer model the singlet - triplet splitting is not renormalized by the inter - dimer coupling @xmath10 and the energy of the triplet excitation is @xmath119 . the second singlet , a bound state of two triplets , is at @xmath120 . to stress the fact that in the two dimer model with a periodic boundary condition the inter - dimer bonds are effectively doubled , we write @xmath121 explicitly . there are two other bound states of two triplets , a triplet at @xmath122 and a quintet at @xmath123 . these energies and the ground state wavefunction are slightly changed by the static dm interactions @xmath124 and @xmath125 . the spin states @xmath126 and @xmath127 are strongly mixed by the inter - dimer @xmath124 since they are degenerate in any field . the states are labelled in fig.[eparaeigenprob ] . the following parameters were used to fit the energy spectra plotted in fig.[baceclevelsprobab ] and [ eparaeigenprob ] . the energy of one - triplet sublevels @xmath128 and @xmath129 gives us @xmath130@xmath2 . to get the singlet @xmath38 at 28.6@xmath2 we use @xmath131@xmath2 . triplet levels are split in zero field by @xmath132@xmath2 . the intra - dimer @xmath7@xmath2 induces an avoided crossing of @xmath68 and @xmath38 . in a simplified picture the one - triplet excitation is the @xmath117 ( or @xmath118 ) state and the excited singlet is @xmath133 . @xmath125 `` flips '' the singlet to the triplet state on one of the dimers and thus couples @xmath68 to @xmath38 . the optical @xmath4-axis phonon bends the cu - o - cu bond in the c - direction . we assume that the bending action of the phonon is the same on both dimers , fig.[model2dimersdynamic ] . as a result the dynamic dm interaction on the dimer ( 1,2 ) is @xmath134 and on the dimer ( 3,4 ) @xmath135 ; the orientation of the cartesian coordinates is the same as in fig.[model2dimersstaticw](b ) . the calculated and the measured transition probabilities as a function of magnetic field are plotted in fig.[baceclevelsprobab](b , d ) for two field orientations . in zero field a line at 25.5@xmath2 is present . the area of this line is the only scaling parameter between the theory and the experiment . note that the transition to the triplet level , which anti - crosses with @xmath38 , is optically active when @xmath136 . when @xmath137 there is no crossing for the optically active triplet level . the overall agreement between the theory and the experiment is good . there is a disagreement between the intensities of the middle and lower triplet components in the theory and in the experiment , fig.[baceclevelsprobab](d ) . in the theory the intensity of the middle component is approximately three times as strong as the lower component while in the experiment they are equal . we tried several changes in our model to make the intensities of the two triplet components more equal and none of them helped . these unfruitful changes were the shift of the phonon frequency , a small out - of - plane component of @xmath63 and an in - plane component of the inter - dimer dm vector @xmath102 . the optical @xmath3-axis phonon bends the cu - o - cu bond in the a - direction and creates a dynamic dm interaction in the c - direction , fig.[model2dimersdynamic ] . if we choose @xmath138 the dynamic dm interaction is created on dimer ( 1,2 ) , @xmath139 . in general , for an arbitrary orientation of @xmath140 in the @xmath5 plane , both dimers will acquire a certain @xmath141 . for the time being we assume @xmath138 . in zero magnetic field the transition to the central triplet component is observed , fig.[eaec4k4spec ] . as the @xmath142 field is turned on , fig.[eparaeigenprob]b , the central line , being a sum of two overlapping transitions , conserves its intensity . the experimentally observed drop in intensity with increasing field is a @xmath22 effect . at 1.8k ( 18 t field ) the intensity is recovered . besides the strong central line there are in zero field two sidepeaks ten times weaker at 22.7 and 25.5@xmath2 corresponding to transitions to the twice degenerate states @xmath34 and @xmath37 . the dynamic dm interactions due to the @xmath3 axis and @xmath4-axis phonons in this @xmath63 orientation give zero intensity for the sidepeaks . the detailed analysis of the mechanism causing these weak transitions is difficult because in other polarizations and field orientations stronger mechanisms are prevailing . the sidepeaks split in the magnetic field and an avoided crossing with @xmath67 and @xmath38 is seen in the experiment . when the magnetic field is in the @xmath5 plane two cases must be considered , @xmath143 and @xmath144 . in fig.[eparaeigenprob](c , d ) the @xmath145 case is shown . here are optically active the triplet levels which anti - cross with the singlet states . in @xmath144 field orientation , fig.[eabbyeigenprob ] , the optically active triplet levels do not anti - cross with the singlet states . the mutual orientation of @xmath63 and @xmath146 is important because @xmath138 creates @xmath147 on the dimer ( 1,2 ) and not on ( 3,4 ) . which set of the two - fold degenerate triplet levels is optically active depends on the relative orientation of @xmath63 and @xmath148 on the dimer where @xmath149 . in fig.[eparaeigenprob ] @xmath150 and in fig.[eabbyeigenprob ] @xmath151 . an additional splitting of @xmath34 and @xmath37 by 0.6@xmath2 seen in fig.[eabbyeigenprob ] is because @xmath63 is out of @xmath5 plane by @xmath152 . we have shown that the first triplet state energy spectra are well described with two static dm interactions , @xmath153 and @xmath154 . the information about @xmath153 and @xmath154 is contained in the position of energy levels and in the fir absorption line intensities . the inter - dimer @xmath153 determines the magnetic field dependence of intensities and the triplet state level energy splitting . the intra - dimer @xmath154 determines the extent of the avoided crossing with @xmath38 and the magnetic field dependence of intensities near the avoided crossing points . over the magnetic field range of our experiment the intensities of the singlet - triplet absorption lines do not depend on the dynamic part of the dm interaction , because the phonon energies are large compared to the triplet state energy . other inter- and intra - dimer dm interaction components besides @xmath153 and @xmath154 have been considered to describe experimental data.@xcite these are the in - plane component of the inter - dimer dm @xmath155 and the symmetry - forbidden intra - dimer dm @xmath156 in the c - direction . we included @xmath155 and @xmath156 in the two dimer model and found that calculations with non - zero @xmath155 and @xmath156 give results contradicting with the experiment . our argument , which is independent of whether a particular infrared transition is allowed or forbidden , relies on the observed and calculated crossing - anti - crossing effects between the triplet and the singlet states . if @xmath157 and @xmath158 then @xmath159 would have an avoided crossing with @xmath38 contradicting the experiment , where @xmath68 anti - crosses with the singlet [ fig.[eparaeigenprob](a ) ] . also @xmath156 does not give any anti - crossing between @xmath38 and @xmath159 or @xmath68 . in high field nonzero @xmath154 creates an avoided crossing between the ground state @xmath160 and the triplet branch @xmath66 as observed in the experiment@xcite while nonzero @xmath155 or @xmath156 do not create an avoided crossing between @xmath160 and @xmath66 or @xmath161 . however , the two dimer model does not predict the experimentally observed@xcite avoided crossing between @xmath160 and @xmath161 . in @xmath162 field orientation both @xmath155 and @xmath156 add , in addition to @xmath154 , to the avoided crossing of one of the triplet components with @xmath38 . the experimental data can be fitted with a single value @xmath163@xmath2 in both field orientations , @xmath162 and @xmath164 . if @xmath155 and @xmath156 were comparable in magnitude to @xmath154 , then the extent of avoided crossing would be different in @xmath162 and @xmath164 field orientations . our conclusion is that the dominant dm interactions are @xmath165@xmath2 and @xmath166@xmath2 . in the magnetization plateau state the lattice parameters of srcu@xmath0(bo@xmath1)@xmath0 may change due to spin - phonon coupling.@xcite our calculation of energy levels did not account for static lattice distortions and therefore we can not make any conclusions about @xmath155 and @xmath156 and the strength of @xmath167 and @xmath168 in high magnetic fields . the intensity of the fir singlet - triplet transitions depend on the strength of the dynamic dm and on the frequency and the oscillator strength of the phonon . since the particular phonons involved in the dynamic dm effect in srcu@xmath0(bo@xmath1)@xmath0 are not known we can give only the relative strength of dynamic dm interactions . the @xmath3- and @xmath4-polarized singlet - triplet transitions have similar oscillator strengths . these are 2.0@xmath169 ( @xmath170 ) and 1.7@xmath169 ( @xmath171 ) if we compare the two lower spectra in fig.[eaec4k4spec ] which have been measured on the same sample by changing the direction of the light polarization . the ratio of the dynamic dm interactions for the two mechanisms is @xmath172 if we assume that @xmath3- and @xmath4-axis phonons have equal frequencies and oscillator strengths . the factor 2 accounts for the @xmath3-axis phonon creating a dynamic dm only on the dimer with its axis perpendicular to @xmath173 . the importance of the staggered @xmath75-tensor in srcu@xmath0(bo@xmath1)@xmath0 was pointed out by miyahara et al.@xcite . the staggered @xmath75-tensor exists in srcu@xmath0(bo@xmath1)@xmath0 because of the buckling of cu - o - b planes below 395k . it mixes singlet and triplet states similar to the static dm interaction @xmath174 . the strength of the staggered @xmath75-tensor interaction can be estimated and we show that its effect on the energy of the spin levels is small compared with the effect of @xmath174 . the zeeman term @xmath175 couples singlet and triplet states on a single dimer and is proportional to @xmath176 , where @xmath177 ( ref.@xcite ) . the angle @xmath178 is the buckling angle of the cu - o - b plane@xcite . the components @xmath179 and @xmath180 of the cu ion @xmath75-tensor are not known but we take @xmath181 and @xmath182 ( table[alllines ] ) and get @xmath183 . the staggered term @xmath175 increases linearly with magnetic field . the largest field where the anti - crossing between @xmath59 and @xmath38 takes place is 5 t . in this field the magnitude of the staggered @xmath75-tensor term in the hamiltonian is 0.05@xmath2 , which is much smaller than the static intra - dimer dm term @xmath7@xmath2 . we conclude that the dominant coupling between the singlet and the triplet is due to the static dm interaction @xmath174 . several states besides the one - triplet excitation are infrared - active ( table[alllines ] ) . we showed that the two dimer model explains well the energies of the one - triplet states and transitions to them . in the two dimer model with @xmath184@xmath2 and @xmath131@xmath2 we get several two triplet states : a singlet , a triplet , and a quintet of two bound triplets at 28.4 , 38.2 , and 57.8@xmath2 , respectively . srcu@xmath0(bo@xmath1)@xmath0 has two low energy singlet states @xmath67 and @xmath185 which both anti - cross with triplet state levels ( fig.[baceclevelsprobab ] and [ eparaeigenprob ] ) . in the two dimer model only one singlet of bound triplets is possible and the anti - crossing occurs only with @xmath37 states . in the experiment an anti - crossing is observed between @xmath38 and @xmath68 , fig.[eparaeigenprob](a ) . the observed anti - crossing between @xmath67 and @xmath66 can not be explained by the two dimer model . in section[dmdiscussion ] we show that other dm interactions besides @xmath103 are weak or absent in srcu@xmath0(bo@xmath1)@xmath0 in the studied @xmath63 range , although they may have proper symmetry to couple @xmath67 and @xmath66 . the energy of the 38.2@xmath2 triplet in the two dimer model is in the range where triplets are present in srcu@xmath0(bo@xmath1)@xmath0 . there is a triplet at 37.5@xmath2 labelled as @xmath60 ( table[alllines ] ) . fir transitions to this state are active in @xmath186 polarization , fig.[eaec4k4spec ] . in @xmath187 the transitions are weaker ( table[alllines ] ) . the @xmath188 level is fir active when @xmath189 and @xmath39 are active when @xmath190 . all this , polarization and magnetic field dependence , is consistent with the dynamic dm mechanism of the fir absorption where the dynamic dm is along the @xmath4 axis . the @xmath3-axis phonon creates a dynamic dm in the direction parallel to the @xmath4 axis . the intra - dimer dynamic dm interaction @xmath191 does not give any transitions to bound states of triplets . we considered a possibility that the @xmath3-axis phonon modulates the static inter - dimer @xmath102 . we found that the pattern of dynamic inter - dimer dm vectors with the same symmetry as @xmath102 [ fig.[model2dimersstaticw](b ) ] gives selection rules that apply to the 37.5@xmath2 @xmath60 triplet . transitions to other states are forbidden in the first order of this dynamic dm interaction . the lattice deformation that creates such a pattern of dynamic dm vectors is of @xmath192 symmetry and is not an optical phonon ; in the @xmath192 symmetry mode cu atoms on @xmath9 bond move along the bond in antiphase . we conclude that the two dimer model is not sufficient to account for transitions to states of bound triplets , except to @xmath193 . quintet states were observed by high field esr.@xcite their extrapolated zero field energies are in the range 46 - 58@xmath2 . there are two @xmath138 singlet excitations at 52.3 and 53.5@xmath2 in this range ( table[alllines ] ) . the quintet ( @xmath194 ) has a @xmath195 spin level which has the same magnetic field dependence of energy as the @xmath196 state . however , the observed singlets at 52.3 and 53.5@xmath2 are not the @xmath195 components of the quintet . if in one @xmath63 field orientation the @xmath195 level is infrared - active then in the @xmath197 rotated field orientation other levels , @xmath198 or @xmath199 , become active . we studied all possible @xmath63 , @xmath173 orientations relative to crystal axes and did not find the splitting of the 52.3 and 53.5@xmath2 excitations in the magnetic field although they are one to two orders of magnitude more intensive than other magnetic excitations in fir spectra . we assigned the @xmath3 axis polarized ( @xmath138 ) 43.0 , 52.3 , and 53.5@xmath2 singlet excitations to magnetic excitations because of the magnetic field and temperature dependence of their energy and intensity.@xcite whether they could be phonons activated by magnetic interactions needs a further study . in srcu@xmath0(bo@xmath1)@xmath0 the ground state is not exactly a product of singlets on dimers as in the shastry - sutherland model , because the intra - dimer dzyaloshinskii - moriya interaction @xmath103 mixes the ground singlet state with the triplet . from the observed anti - crossing between @xmath68 and @xmath38 we get @xmath7@xmath2 this is comparable to the inter - dimer dm , @xmath6@xmath2 , which determines the triplet state energy level zero field splitting . both @xmath102 and @xmath103 determine the magnetic field dependence of the absorption line intensities . although magnetic dipole singlet - triplet transitions are allowed by @xmath103 , the experimentally observed polarization and magnetic field dependencies of absorption line intensities are not described by this interaction . instead , singlet - triplet transitions are allowed by the dynamic dm mechanism where the electric field component of fir light couples to a non - symmetric phonon , which creates the dm interaction . there are two dynamic dm mechanisms in srcu@xmath0(bo@xmath1)@xmath0 . in one case the fir light couples to an @xmath3-axis phonon and in the other case to a @xmath4-axis phonon . this is consistent with the calculations of cpas and ziman@xcite who used a two dimer model in the @xmath200 limit . the experiment also yielded information about higher triplet and singlet excitations . several of these absorption lines are identified as electric dipole transitions . the two dimer cluster is too small to describe these transitions . also , we had to use renormalized values of @xmath9 and @xmath10 to calculate the energy levels because the actual spin excitations are delocalized over a larger cluster . obviously a bigger cluster is needed for proper calculation of magnetic excitations in srcu@xmath0(bo@xmath1)@xmath0 . nevertheless , the two dimer model gives us a good description of the one - triplet excitation . we thank g.blumberg and o.cpas for fruitful discussions . this work was supported by the estonian science foundation grants nos . 4926 , 4927 , and 5553 . and @xmath113 . ( a ) dimer @xmath113 and four nearest - neighbor dimers . the thin dashed line shows the two dimer cluster boundary . thin solid lines show the distortion of cu - cu superexchange bonds due to the buckling of cu - o - b planes . thick solid and dashed lines are the inter- and intra - dimer superexchange constants @xmath9 and @xmath10 ; inter - dimer dm vectors ( @xmath102 , solid arrow ) are in the @xmath4 direction and intra - dimer dm vectors ( @xmath103 , empty arrow ) in the @xmath5 plane along @xmath3 and @xmath201 axis . ( b ) the two dimer model after the periodic boundary condition has been applied ; inter - dimer interactions have doubled . , width=325 ] polarization at 4.4k ; ( a ) , ( b ) @xmath203 ; ( c ) , ( d ) @xmath204 . solid lines are the results of the calculation based on the two dimer model : @xmath20524@xmath2 , @xmath2069.8@xmath2 , @xmath2071.4@xmath2 , and @xmath2081.8@xmath2 . dashed lines in panels ( a ) and ( c ) are fits with parameters given in table[alllines ] . , width=672 ] polarization at 4.4k ; ( a ) , ( b ) @xmath203 ; ( c ) , ( d ) @xmath204 . solid lines are the results of the calculation based on the two dimer model : @xmath20524@xmath2 , @xmath2069.8@xmath2 , @xmath2071.4@xmath2 , and @xmath2081.8@xmath2 . dashed lines in panels ( a ) and ( c ) are fits with parameters given in table[alllines ] . the solid line in panel ( b ) is the sum of two theoretical line areas of @xmath160 to @xmath128 and to @xmath129 transitions shown by dashed lines . dashed lines in ( d ) are eye guides ( see text ) . the 18 t point in panels ( a ) and ( b ) was measured at 1.8k.,width=672 ] and @xmath209 configuration at 4.4k . the lines are results of the calculation based on the two dimer model and dynamic dm interaction . the additional splitting of triplet components ( triangles ) is caused by the magnetic field @xmath63 being misaligned by @xmath152 out of the @xmath5 plane.@xcite in panel ( b ) the line area ( triangles up or triangles down ) is a sum of line areas of split components . , width=325 ] ( solid arrow ) creates an intra - dimer dm interaction @xmath210 ( empty arrow ) . the @xmath4-axis phonon creates a dynamic dm interaction on both dimers while the @xmath3-axis phonon affects the dimer @xmath111 only . , width=325 ]

we have studied spin excitation spectra in the shastry - sutherland model compound srcu@xmath0(bo@xmath1)@xmath0 in magnetic fields using far - infrared fourier spectroscopy . the transitions from the ground singlet state to the triplet state at 24@xmath2 and to several bound triplet states are induced by the electric field component of the far - infrared light . to explain the light absorption in the spin system we invoke a dynamic dzyaloshinskii - moriya ( dm ) mechanism where light couples to a phonon mode , allowing the dm interaction . two optical phonons couple light to the singlet to triplet transition in srcu@xmath0(bo@xmath1)@xmath0 . one is @xmath3-polarized and creates an intra - dimer dynamic dm along the @xmath4 axis . the other is @xmath4-polarized and creates an intra - dimer dynamic dm interaction , it is in the @xmath5 plane and perpendicular to the dimer axis . singlet levels at 21.5 and 28.6@xmath2 anti - cross with the first triplet as is seen in far - infrared spectra . we used a cluster of two dimers with a periodic boundary condition to perform a model calculation with scaled intra- and inter - dimer exchange interactions . two static dm interactions are sufficient to describe the observed triplet state spectra . the static inter - dimer dm in the c - direction @xmath6@xmath2 splits the triplet state sub - levels in zero field [ cpas et al . , phys . rev . lett . * 87 * , 167205 ( 2001 ) ] . the static intra - dimer dm in the @xmath5 plane ( perpendicular to the dimer axis ) @xmath7@xmath2 , allowed by the buckling of cubo@xmath1 planes , couples the triplet state to the 28.6@xmath2 singlet as is seen from the avoided crossing .

cemento - ossifying fibromas are benign fibro - osseous tumors that are composed of fibrous tissue and a variable mixture of calcified materials . they are well - defined unilocular or multilocular lesions with slowly progressing enlargement of the affected bone . the most frequent site is the mandibular premolar and molar areas , and the tumor has a definite female predilection . occasionally , it may grow to a massive size and cause serious cosmetic and functional problems , and there are rare reports of lesions behaving in an aggressive fashion1 . low - grade lesions are rare and include well - differentiated intramedullary osteosarcomas and parosteal osteosarcomas2 we report a case of low - grade osteosarcoma in the mandible that was transformed from a recurrent cemento - ossifying fibroma . this is the first reported case of the transformation of cemento - ossifying fibroma into malignant low - grade central osteosarcoma . a 45-year - old female patient was referred for a radiolucent lesion of the left posterior mandible , with complaints of a three - month history gingival swelling and tooth pain in the left mandibular second premolar . on intraoral examination , the overlying mucosa was intact with no paresthesia on the left lower lip . a panoramic radiograph showed external root resorption of the second molar and a relatively well - defined radiolucent lesion involving the posterior mandibular body and ramus.(fig . 1 ) computed tomography ( ct ) imaging showed buccolingual cortical expansion and a soft tissue mass.(fig . 1 ) the surrounding soft tissue did not appear to be involved . under local anesthesia , extraction of the second molar was performed , and a biopsy was taken below the extraction socket for histopathological examination . histopathological examination showed dense fibroblastic proliferation , woven bone , and cementum - like material.(fig . the surgical specimen was sent to a pathologist , and the pathologist recommended close follow - up because of the high cellularity of the specimen . five months after the first operation , the patient complained of tooth pain in the left mandibular second premolar and underwent root canal treatment . periodic follow - up was performed , and there were no signs of recurrence on either clinical or radiographic examination for 16 months . after 16 months , however , follow - up panoramic radiograph and ct displayed signs of recurrence , including a mixed high - attenuation intrabony lesion and a partially multilocular lesion . mass excision was performed under local anesthesia , the surgical specimen was submitted for histological examination ; the pathological diagnosis was cemento - ossifying fibroma . one year after the second operation , the patient complained of discomfort in the left mandibular canine area , and ct revealed expansion of the lesion and signs of recurrence . intentional root canal treatment of the left mandibular first premolar and mass excision were performed under general anesthesia.(fig . 3 ) the pathological diagnosis was the same as previously , but the surgical specimen showed high cellularity and an infiltrative growth pattern into normal bone tissue without mitotic figures or cellular atypia . three months after the third operation , tumor recurrence was suspected at the parasymphysis area on follow - up radiograph ( fig . 4 ) , and a biopsy was taken from the buccal side of the lesion . the specimen showed minimal cellular atypia and irregular bony trabeculae with few mitotic figures ( fig . no regional or distant metastasis was shown on magnetic resonance imaging or positron emission tomography - ct imaging . the patient underwent wide excision , segmental mandibulectomy , and reconstruction with fibula free flap.(fig . cemento - ossifying fibromas are benign fibro - osseous lesions of the jaw which have been described as demarcated or rarely encapsulated neoplasms consisting of fibrous tissue and various amounts of mineralized material such as bone and/or cementum4 . radiologically , cemento - ossifying fibromas are initially characterized by well - differentiated osteolytic images5 . as they evolve they are benign lesions , but sometimes may behave in an aggressive manner and cause extensive bone destruction6 . in aggressive cases , en bloc resection or partial resection of the jaw no cases of aggressive cemento - ossifying fibroma transforming into osteosarcoma have been previously documented . osteosarcomas of all sites account for 40%-60% of primary malignant bone tumors , and osteosarcomas of the mandible affect approximately 1 in 10 million persons per year , mostly young adults8 . the histopathology of low - grade central osteosarcoma usually shows bundles of spindle cells with minimal cytological atypia , rare mitotic figures , and a variable amount of osteoid formation9 . resection with wide surgical margins is the most important factor in determining prognosis and provides a 5-year survival rate of 80% . adjuvant chemotherapy or radiotherapy seems to be inefficacious in cases of low - grade central osteosarcoma2 . in our case , the patient was treated with mass excision several times over a period of two years and eight months because of recurrent cemento - ossifying fibroma . recurrence of these benign tumors following surgery is considered rare , although the reported recurrence rate varies between 0% and 30%4 . this is the first reported case of low - grade osteosarcoma arising from cemento - ossifying fibroma , so there are insufficient data for evaluating this malignant transformation . however , oral and maxillofacial surgeons should be aware of the rare possibility that cemento - ossifying fibroma can transform into osteosarcoma and that careful diagnosis and regular follow - up are required in patients with cemento - ossifying fibromas .

cemento - ossifying fibromas are benign tumors , and , although cases of an aggressive type have been reported , no cases of cemento - ossifying fibroma transforming into osteosarcoma have been documented previously . low - grade osteosarcoma is a rare type of primary bone tumor , representing 1%-2% of all osteosarcomas . a 45-year - old female patient was diagnosed with cemento - ossifying fibroma , treated with mass excision several times over a period of two years and eight months , and followed up . after biopsy gathered because of signs of recurrence , she was diagnosed with low - grade osteosarcoma . the patient underwent wide excision , segmental mandibulectomy , and reconstruction with fibula free flap . the aim of this report is to raise awareness of the possibility that cemento - ossifying fibroma can transform into osteosarcoma and of the consequent necessity for careful diagnosis and treatment planning .

osteoporosis is recognised as a major public health problem through its association with low trauma or fragility fracture . osteoporotic hip fracture is an established health problem in the west over the last six decades and is increasingly being recognised as a growing problem in asia . with a rising life expectancy throughout the globe , the number of elderly individuals is increasing in every geographical region ; the incidence of hip fracture is estimated to rise from 1.66 million in 1990 to 6.26 million in 2050 . all osteoporotic fractures increase patient morbidity ; however , the fractures of hip and vertebrae are associated with significant mortality . hip fracture incidence increases exponentially with age and more so in women . with changing world population dynamics it has been estimated that more than half of these fractures will be seen in asia by year 2050 . the exact reasons for this geographic variation are ill understood but genetic factors , less bone mineral content , an aging population and environmental factors such as dietary factors and vitamin d levels are important in the pathogenesis of hip fracture . understanding this changing epidemiology of hip fracture is therefore essential to develop strategies for the future with a special emphasis on asia . keywords that were employed included hip fracture , incidence rate , geographic variation , osteoporosis , and epidemiology . the articles were chosen based on the basis of ( 1 ) focus : studies that were said to specifically focus on geographic variation in hip fracture from different continents with a focus on asia ; ( 2 ) language : studies that were in english ; ( 3 ) methods : studies that used statistical tests to examine hip fracture incidence rates . age - standardized hip fracture rates ( per 100,000 ) across different continents and asian countries are given in table 1 and figure 1 , respectively . the highest hip fractures are seen in us populations but the recent trends show that these fracture rates have either stabilized or decreased in the last two decades . in a population - based study from minnesota it has been observed that annual age - adjusted incidence rates among women rose rapidly until 1950 only to fall slowly thereafter . age - adjusted rates in men rose more steadily before beginning a downturn after 1980 . a californian study looked at hip fracture rates between 1983 and 2000 , with particular interest in the hispanic population , the largest , fastest growing ethnic minority in the united states . hip fractures were identified using the annual hospital patient discharge database . among non - hispanic white women in california the standardised annual hip fracture rates for those 55 years old and over fell steadily over the past two decades by 0.6% per year in women and 0.5% in men . by contrast annual fracture rates amongst hispanic women increased by 4.9% per year and 4.2% in men . this supports the hypothesis that residence in early life has a much greater association with variation in hip fracture rates that does current region of residency . another explanation is that hispanic men and women have been shown to partake in less physical activity and have a greater risk of nutritional deficits than non - hispanic whites . in a recently published study by brauer and coworkers , it was concluded that in the us the annual mean number of hip fractures was 957.3 per 100,000 for women and 414.4 per 100,000 for men . the age - adjusted incidence of hip fracture increased from 1986 to 1995 and then steadily declined from 1995 to 2005 . the age - adjusted fracture incidence in canada is 86.4 per 100,000 in women and 53.4 per 100,000 in men . on comparison with data from the us , the overall fracture rate in canadian women was 30% lower than that in us women in 2001 and 26% lower than that in german women in 2004 . canadian men showed similar overall hip fracture rates to american men prior to age 80 years but 26% lower rate after 80 years . in europe , there are a large number of studies looking at the incidence as well as secular trends in this geographically northern region . the incidence rates vary from north to south europe , the highest being in sweden and norway and the lowest in france and switzerland . from norway the reported age standardised annual incidence rates of hip fracture are 920 per 100,000 in women and 399.3 per 100,000 in men and those in switzerland are 346 per 100,000 and 137.8 per 100,000 in women and men , respectively . studies from malmo , sweden showed an exponential increase in hip fracture incidence from 1950 to 1985 in both men and women over age 50 , increasing from an annual age - adjusted incidence of 150 to 390 per 100,000 in men and 300 to 830/100,000 in women . a recent study from the uk looked at hospital episode statistics from 19891998 . age - standardised incidence rates increased by 32% in women and 38% in men to 1991 - 92 and thereafter remained stable . in the netherlands between 1972 and 1987 the age - adjusted incidence of hip fractures rose linearly from 479/100,000 to 669/100,000 per year in women and from 198/100,000 to 308/100,000 in men aged 65 years and over using the dutch medical registry . european data on hip fracture shows a clear north - south gradient with the highest hip fractures occurring in scandinavian countries and the lowest in spain , and one of the reasons may be that colder winter induces more falls in an elderly population . the age - adjusted rates from australia are 130/100,000 person years in men and 390/100,000 person years in women with no significant change over the last two decades . women aged 6575 years were the only age specific group with a 1% decline in annual incidence of hip fracture and the rest being unchanged during the period . this may be due to different methods used for fracture incidence measurement . in a study published from mexico in 2005 , the annual rates of hip fracture in the two public health care systems were 169 in women and 98 in men per 10,000 person years . overall the fracture rates are much less than those seen in us and europe , and the major reason is shorter life span . a major study concluded that in a japan population aged 35 years or older the crude incidence of hip fracture was 244.8 per 100,000 person years from 2004 to 2006 , and the gender - specific incidence was 99.6 per 100,000 person years for men and 368 per 100,000 person years for women . when data was analysed and compared with that from 30 years ago it was also concluded that there is an increasing incidence of hip fracture in japanese populations . the highest incidence of hip fracture from asia has been reported from singapore . a study by koh et al . revealed that hip fracture rates from 1991 to 1998 ( per 100,000 ) were 152 in men and 402 in women , and this was 1.5 and 5 times higher than corresponding rates in 1960s . since 1960 the main increase in hip fracture rates has been seen in chinese and malays with rates in indian ethnic group appearing to decrease . incidence rates of hip fracture from hong kong are 110 per 100,000 in women and 50 per 100,000 in men as per data from public hospitals in 1995 . secular trends on hip fracture from hong kong suggest that over the last three decades the age specific incidence increased 2.5 fold in women and 1.7-fold in men . the incidence rates were found to be similar to those seen in wessex health region of uk . in beijing , china hip fracture incidence was obtained from admissions between 1988 and 1992 within the 76 city hospitals . it was presumed that all the fracture cases from beijing go to these public hospitals only . the majority of data from the middle east is available from iran from the iranian multicenter study on accidental injuries . this study reported age - standardized incidence rates of 127.3 per 100,000 person years in men and 164.6 per 100,000 person years in women which are much lower than those of all the western countries and us population . there need to be more studies from other parts of asia especially from india in order to understand the geographic variation in hip fracture in this region as a whole . conducted a study in cameroon by documenting all patients aged 35 years and older admitted to the two main urban hospitals in cameroon following a diagnosis of fracture during two years . using the 1997 estimates of population , the incidence of low energy trauma fractures ( per 100,000 persons over 35 years ) was 4.1 in women and 2.2 in men at hip . similar low fractures rates have been reported from morocco in 2005 . to investigate the geographic variation in different parts of the world and whether this is genuine or related to error in data collection , schwartz et al . carried out a cross - national study of hip fracture in five geographic areas beijing , china ; budapest , hungary ; hong kong ; porto alegre , brazil ; reykjavik , iceland during the years 19901992 . cases of hip fracture among women and men of 20 years and older were identified using hospital discharge data in conjunction with medical records , operating room logs , and radiology logs . estimated rates varied widely , with beijing reporting the lowest rates ( 45.4 per 100,000 in men and 39.6 ) and reykjavik the highest rates ( men = 141.3 ; women = 274.1 ) . rates were higher for the women than for the men in all areas except beijing . the study demonstrated large differences in hip fracture incidence rates , with age - adjusted incidence rates in women being 6 times higher and in men over 3 times higher in reykjavik compared with beijing . results of this study indicate substantial limitation in relying on the hospital discharge data alone to estimate hip fracture incidence rates but the error found in the discharge lists is smaller than the large international variation found . the study concluded that the differences reported among countries mainly reflect genuine variation in the hip fracture incidence rates . the influence of ethnicity on risk of osteoporotic fractures was analysed by our group ( unpublished ) . the rates vary considerably according to the geographic area and race and may vary widely within the same country and within populations of a given sex and race . in europe , hip fracture rates vary 7-fold between countries . in general people who live in latitudes the highest rates of hip fracture are seen in caucasians living in northern europe , especially scandinavians . a study from 1989 found that the age - adjusted 1-year cumulative incidence of hip fracture in norway was 903/100,000 for women and 384/100,000 for men . the rates are intermediate in asians , china and kuwait , and the lowest in black populations . while studies in central norway suggest a stabilisation in fracture rates in recent years , a californian study published in 2004 reported a doubling of hip fracture rates in hispanics while no significant change occurred among black or asian men or women . many of the lower incidence rates seen in the developing countries can be partially explained by lower life expectancy ; in latin america only 5.7% of the population is over 65 . reduced longevity may also be the explanation for the low fracture rates observed in morocco . the reasons for these geographic and ethnic variations are ill understood but factors which may be responsible are genetic factors and environmental factors . those factors studied so far , such as alcohol consumption , smoking , activity levels , obesity , and migration status , have not explained these trends however . reduced lifespan in african and asian population may be one important attribute for the lower incidence of hip fracture in these regions . further research is clearly needed to explain these important environmental factors . to conclude , osteoporotic hip fractures are responsible for both morbidity and mortality among an elderly population and consume a large amount of health care resources in europe and the usa . however , a recent decline in the hip fracture incidence in these regions is good news for health authorities but that is not true for the rest of the world . with a changing population profile and increasing elderly population in asian countries there will be a shift of focus from europe and us to asia ; health authorities need to prepare to face this challenge in the next four decades .

studies over the last few decades have demonstrated geographic variation in the incidence of hip fracture across continents and among different parts of the same region . this paper studies the epidemiology of hip fracture worldwide , with special emphasis on the geographic variation among asian countries . using the pubmed database , keywords that were employed included hip fracture , incidence rate , geographic variation , osteoporosis , and epidemiology . articles were chosen based on the basis of ( 1 ) focus : studies that were said to specifically focus on geographic variation in hip fracture from different continents with a focus on asia ; ( 2 ) language : studies that were in english ; ( 3 ) methods : studies that used statistical tests to examine hip fracture incidence rates . the highest hip fracture rates are seen in scandinavian countries and the us and the lowest in african countries . fracture rates are intermediate in asian populations . among different ethnic populations , the highest fracture rates are seen in caucasians and the lowest in blacks . there is also a north - south gradient , particularly in europe , where more hip fractures occur in north europe compared to the south .

transcranial magnetic stimulation ( tms ) was first described by barker et al . as a non - invasive , painless way to stimulate the human brain . tms has been applied to many neurological and psychiatric disorders to explore the pathophysiology of these conditions , the clinical diagnostic utility of different tms techniques and their use as a possible treatment [ 2 , 3 ] . tms is based on a time - varying magnetic field that generates an electric current inside the skull , which can be focused and restricted to small brain areas by appropriate stimulation coil geometry and size . this current , if applied repetitively [ repetitive tms ( rtms ) ] , induces cortical modulation that lasts beyond the time of stimulation . the effect of this cortical modulation depends on the frequency of the stimulation used : increased and decreased excitability result from low - frequency ( lf ) and high - frequency ( hf ) tms , respectively . rtms can thus guide brain plasticity and consequently can be used to treat chronic pain , a disorder that is associated with substantial reorganization of cns activity . the use of rtms in the primary motor cortex ( m1 ) to control pain was first reported by migita et al . , who showed pain reduction in two patients treated by lf ( < 0.2 hz ) rtms . since then , growing evidence has supported the potential beneficial effects of motor cortex rtms for pain control in chronic pain patients [ 6 , 7 ] . however , many questions remain to be addressed before any firm conclusions about this therapy can be drawn . several studies attempted to explore the mechanisms of m1 interaction for pain control using objective methods , including laser - evoked potentials , which are a reliable measure of nociceptive pathways function . in normal subjects , lf tms of the motor cortex reduced subjective pain and cortical activation induced by intradermal injection of capsaicin , but increased evoked responses and subjective pain related to a - delta fibers activation by laser stimuli . hf tms of the motor cortex increased the cold pain threshold and tolerance of painful mechanical stimuli in normal study participants . moreover , the voluntary movement preparation inhibits subjective pain and evoked responses induced by laser stimuli , thus confirming that activation of the motor cortex can reduce the nociceptive cortical recruitment induced by acute painful stimulation . in chronic neuropathic pain patients , the activation of the motor cortex by hf rtms seems to alleviate painful symptoms , probably through the restoration of gabaergic inhibition in the nociceptive cortex . accordingly , hf rtms of m1 reduced vertex leps and laser pain in a group of chronic neuropathic pain patients . migraine is an incapacitating disorder of neurovascular origin , and prophylactic treatments are often inadequate to prevent it from becoming chronic . in some instances , in addition , dorsolateral prefrontal cortex ( dlpfc ) modulation has a positive effect in chronic migraine patients . however , the altered cortical excitability that characterizes migraine can make the effects of rtms unpredictable . given that in migraine patients lep pattern seems to reflect the modality of nociceptive cortex activation as well as the effects of treatments , we aimed to examine the effects of hf rtms of the primary motor cortex on subjective pain and evoked responses induced by laser stimulation of the contralateral hand and trigeminal zone in a cohort of migraine patients without aura during the inter - critical phase , and to compare the effects with those of non - migraine , healthy controls . twelve healthy , right - handed subjects ( 10 females ) from 21 to 38 years of age ( mean 32.2 2.9 ) participated in the study . the migraine group consisted of 13 right - handed migraine patients without aura ( 11 females ) ranging in age from 21 to 39 years ( mean 32.6 4.1 ) and that had been diagnosed according to the international classification of headache disorders ( ichd ii ) criteria ( cod . migraine patients were recorded during the inter - critical phase at least 72 h after the last attack and 48 h before the next one , as ascertained by a telephone interview . exclusion criteria were as follows : preventive treatment for migraine or treatment with any drug which acts on the snc in the previous 3 months , treatment with any analgesic drug in the pervious 72 h , co - morbidity for general medical and neurological diseases , and any other psychiatric disease as described by the diagnostic and statistical manual of mental disorders ( dsm - iv ) . patients and controls were similar in age [ anova f = 0.23 , non - significant ( ns ) ] and education ( mean number of years of education was 12.1 0.8 and 12.8 0.5 for patients and controls , respectively ; anova f = 0.12 , ns ) . the selected migraine patients reported a mean of 3.2 1.1 days with headache per month over the previous 3 months . all subjects were comfortably seated in a chair and instructed to be as relaxed as possible . the rtms was delivered over the hand motor cortex of the left hemisphere through a water - cooled figure eight coil powered by a magpro x 100 ( medtronic ) magnetic stimulator . the stimulating coil was placed over the site that optimally elicited responses in the contralateral abductor pollicis brevis ( abp ) target muscle ( termed the apb hotspot ) . the motor threshold ( mt ) was measured as the minimum stimulus intensity that elicited a motor evoked potential ( mep ) of at least 50 v in 5 or more of 10 consecutive stimulations in the right apb hot spot . to establish the motor threshold , electromyography ( emg ) signals were recorded from the right apb muscle using 0.9-cm diameter ag agcl surface electrodes placed 3 cm apart over the center and tendon of the muscle . the emg activity was recorded with a band - pass filter between 10 and 1,000 hz and a display gain ranging from 50 to 200 v / cm . each rtms session consisted of 1,800 stimuli divided in 12 trains at a frequency of 5 hz and 90% mt intensity , and stimuli were separated by a 10-s pause . sham ( control ) rtms was performed at the same stimulation position with the coil tilted approximately 45 over the scalp . during lep recording , the subjects lay on a couch in a warm , semi - dark room and were awake and relaxed with their eyes open . leps were obtained using surface recording electrodes placed at cz and pz , with reference to the nasion , and at the t3 and t4 positions with reference to the fz derivation ( 10 - 20 international system ) , by means of a micromed eeg apparatus ( micromed brain quick , mogliano veneto , italy ) . an additional electrode was positioned above the right eyebrow for electro - oculogram ( eog ) recording . cutaneous heat stimuli were delivered by a co2 laser [ wavelength 10.6 um , 2 mm beam diameter ( elen , florence , italy ) ] on the dorsum of the right hand and the right supraorbital zone . the laser pain threshold ( pth ) was established in the basal session by delivering a series of stimuli at increasing and decreasing intensities using 0.5 w steps . the pain threshold was the lowest intensity that enabled at least 50% of the stimuli to be perceived as a painful pinprick using a 10-point verbal analogical scale in which 0 corresponds to no sensation , 4 to the pain threshold and 10 to intolerable pain . the basal laser intensity was set at two steps over the pain threshold . in rtms and sham sessions , the mean laser intensity was 8.1 0.2 w in controls and 7.9 0.3 w in migraine patients ( anova f = 0.23 , ns ) . to verify the modifications induced in the sham and the rtms sessions , we asked all subjects to rate the laser pain on a 0100 visual analogical scale ( vas ) at the end of a stimulation series , where 0 corresponds to no pain and 100 to the worst pain conceivable . in the basal , sham and rtms sessions , the dorsum of the right hand and the right supraorbital zone was stimulated in random order by two consecutive series of 25 stimuli with an isi of 10 s and an inter - series interval of 5 min . an investigator blind to the clinical condition analyzed leps in 1 s intervals with 100 ms pre - stimulus time at a sampling rate of 512 hz using advanced source analysis ( asa ) software ( version 4.6 by ant ) . all runs containing transient responses exceeding 65 mv in each recording channel were excluded from the average by an automatic artifact rejection algorithm . in addition , further artifacts were visually inspected , and an average of at least 15 artifact - free responses was obtained off - line for each stimulation series . for each stimulation site , an average across the two series of stimuli was obtained for the right hand and right supraorbital zone . leps were identified based on their latency and distribution , and three responses were labeled according to valeriani et al . . the n2a ( namely n2 ) and p2 components were analyzed at the vertex ( cz ) , and the n1 component was analyzed at the t3fz trace . the absolute latencies of the scalp potentials were measured at the highest peak of each response component , and the amplitude of each wave was measured from the baseline . the baseline was measured automatically by calculating the average signal of the whole sweep and subtracting it from the trace ( asa - vers . in addition , the peak - to - peak amplitude was taken into consideration for the vertex biphasic lep component ( n2p2 ) . all subjects were informed of the experimental procedure and signed an informed consent document that was approved by the bari policlinico general hospital ethic committee . after a basal lep evaluation , each subject was submitted to the rtms and sham sessions in a random sequence over two consecutive days . in the rtms and sham sessions , leps were obtained immediately after the tms modulation by stimulating the right hand and supraorbital zones in a random order using the procedure outlined above . the one - way anova was used to analyze the data where the lep latency and amplitude and the laser pain rating were variables , the session ( baseline , real rtms and sham rtms ) within subject factor . to compare the variables across the three different sessions , a post hoc multiple comparison bonferroni test in addition , we computed the percent variation of n2p2 amplitude between the sham and the basal , the rtms and the basal and the rtms and the sham conditions , and then we compared these values between patients and controls , performing the student s t test , corrected for multiple comparisons . twelve healthy , right - handed subjects ( 10 females ) from 21 to 38 years of age ( mean 32.2 2.9 ) participated in the study . the migraine group consisted of 13 right - handed migraine patients without aura ( 11 females ) ranging in age from 21 to 39 years ( mean 32.6 4.1 ) and that had been diagnosed according to the international classification of headache disorders ( ichd ii ) criteria ( cod . migraine patients were recorded during the inter - critical phase at least 72 h after the last attack and 48 h before the next one , as ascertained by a telephone interview . exclusion criteria were as follows : preventive treatment for migraine or treatment with any drug which acts on the snc in the previous 3 months , treatment with any analgesic drug in the pervious 72 h , co - morbidity for general medical and neurological diseases , and any other psychiatric disease as described by the diagnostic and statistical manual of mental disorders ( dsm - iv ) . patients and controls were similar in age [ anova f = 0.23 , non - significant ( ns ) ] and education ( mean number of years of education was 12.1 0.8 and 12.8 0.5 for patients and controls , respectively ; anova f = 0.12 , ns ) . the selected migraine patients reported a mean of 3.2 1.1 days with headache per month over the previous 3 months . all subjects were comfortably seated in a chair and instructed to be as relaxed as possible . the rtms was delivered over the hand motor cortex of the left hemisphere through a water - cooled figure eight coil powered by a magpro x 100 ( medtronic ) magnetic stimulator . the stimulating coil was placed over the site that optimally elicited responses in the contralateral abductor pollicis brevis ( abp ) target muscle ( termed the apb hotspot ) . the motor threshold ( mt ) was measured as the minimum stimulus intensity that elicited a motor evoked potential ( mep ) of at least 50 v in 5 or more of 10 consecutive stimulations in the right apb hot spot . to establish the motor threshold , electromyography ( emg ) signals were recorded from the right apb muscle using 0.9-cm diameter ag agcl surface electrodes placed 3 cm apart over the center and tendon of the muscle . the emg activity was recorded with a band - pass filter between 10 and 1,000 hz and a display gain ranging from 50 to 200 v / cm . each rtms session consisted of 1,800 stimuli divided in 12 trains at a frequency of 5 hz and 90% mt intensity , and stimuli were separated by a 10-s pause . sham ( control ) rtms was performed at the same stimulation position with the coil tilted approximately 45 over the scalp . during lep recording , the subjects lay on a couch in a warm , semi - dark room and were awake and relaxed with their eyes open . leps were obtained using surface recording electrodes placed at cz and pz , with reference to the nasion , and at the t3 and t4 positions with reference to the fz derivation ( 10 - 20 international system ) , by means of a micromed eeg apparatus ( micromed brain quick , mogliano veneto , italy ) . an additional electrode was positioned above the right eyebrow for electro - oculogram ( eog ) recording . cutaneous heat stimuli were delivered by a co2 laser [ wavelength 10.6 um , 2 mm beam diameter ( elen , florence , italy ) ] on the dorsum of the right hand and the right supraorbital zone . the laser pain threshold ( pth ) was established in the basal session by delivering a series of stimuli at increasing and decreasing intensities using 0.5 w steps . the pain threshold was the lowest intensity that enabled at least 50% of the stimuli to be perceived as a painful pinprick using a 10-point verbal analogical scale in which 0 corresponds to no sensation , 4 to the pain threshold and 10 to intolerable pain . the basal laser intensity was set at two steps over the pain threshold . in rtms and sham sessions , the mean laser intensity was 8.1 0.2 w in controls and 7.9 0.3 w in migraine patients ( anova f = 0.23 , ns ) . to verify the modifications induced in the sham and the rtms sessions , we asked all subjects to rate the laser pain on a 0100 visual analogical scale ( vas ) at the end of a stimulation series , where 0 corresponds to no pain and 100 to the worst pain conceivable . in the basal , sham and rtms sessions , the dorsum of the right hand and the right supraorbital zone was stimulated in random order by two consecutive series of 25 stimuli with an isi of 10 s and an inter - series interval of 5 min . an investigator blind to the clinical condition analyzed leps in 1 s intervals with 100 ms pre - stimulus time at a sampling rate of 512 hz using advanced source analysis ( asa ) software ( version 4.6 by ant ) . all runs containing transient responses exceeding 65 mv in each recording channel were excluded from the average by an automatic artifact rejection algorithm . in addition , further artifacts were visually inspected , and an average of at least 15 artifact - free responses was obtained off - line for each stimulation series . for each stimulation site , an average across the two series of stimuli was obtained for the right hand and right supraorbital zone . leps were identified based on their latency and distribution , and three responses were labeled according to valeriani et al . . the n2a ( namely n2 ) and p2 components were analyzed at the vertex ( cz ) , and the n1 component was analyzed at the t3fz trace . the absolute latencies of the scalp potentials were measured at the highest peak of each response component , and the amplitude of each wave was measured from the baseline . the baseline was measured automatically by calculating the average signal of the whole sweep and subtracting it from the trace ( asa - vers . in addition , the peak - to - peak amplitude was taken into consideration for the vertex biphasic lep component ( n2p2 ) . all subjects were informed of the experimental procedure and signed an informed consent document that was approved by the bari policlinico general hospital ethic committee . after a basal lep evaluation , each subject was submitted to the rtms and sham sessions in a random sequence over two consecutive days . in the rtms and sham sessions , leps were obtained immediately after the tms modulation by stimulating the right hand and supraorbital zones in a random order using the procedure outlined above . the one - way anova was used to analyze the data where the lep latency and amplitude and the laser pain rating were variables , the session ( baseline , real rtms and sham rtms ) within subject factor . to compare the variables across the three different sessions , a post hoc multiple comparison bonferroni test in addition , we computed the percent variation of n2p2 amplitude between the sham and the basal , the rtms and the basal and the rtms and the sham conditions , and then we compared these values between patients and controls , performing the student s t test , corrected for multiple comparisons . at both the hand and face levels , no significant difference were observed in the lep latency across three sessions either in migraine patients or in control subjects ( table 1 ) . in patients and controls , the laser pain rating showed a slight and non - significant reduction in rtms and sham sessions with respect to the basal session , and this reduction was more evident at the face level ( fig . 1 ; table 2 ) . the n1 amplitude seemed not to be significantly modified by sham sessions or rtms at the hand and trigeminal levels in patients and controls ( fig . both rtms and sham sessions caused a slight n1 reduction with respect to the basal condition ( fig . the n2p2 vertex complex appeared significantly modified across the different sessions at the hand level ( figs . 2a , 3 ; table 2 ) . in migraine patients , the sham rtms caused a significant reduction in the vertex wave compared to the basal condition , but bonferroni tests revealed that the real rtms reduced more efficiently leps than sham treatment ( fig . 2a ; table 2 ) . in control subjects , n2p2 amplitude was significant reduced by rtms compared to the basal condition , but no significant change was detectable between basal versus sham and sham versus rtms conditions ( fig . 2a ; table 2 ) . at the trigeminal level , anova analysis revealed that the session factor caused a significant change in the n2p2 amplitude , with a difference between the two groups ( fig . in fact , while in control subjects , the lep amplitude was slightly increased in the sham condition and reduced in the rtms session , in the migraine patients the sham treatment provoked a significant reduction in the vertex complex , and this reduction was even greater following rtms ( figs . in migraine group , the reduction of n2p2 amplitude prevailed with respect to controls , in rtms versus basal condition at the hand level , and in sham versus rtms , rtms versus basal and rtms versus sham condition at the face level ( fig . 4).table 1mean values standard deviations ( sd ) of laser - evoked potentials latencies ( lep ) , expressed in ms , in control subjects ( n = 12 ) and migraine patients ( n = 13)lep latencies ( ms)n1n2p2meansdmeansdmeansdhand control subjects basal179.3022.61243.6731.40386.3329.93 sham179.3334.06234.9037.88358.4036.32 rtms178.2827.62234.0036.85352.0046.44 migraine patients basal162.9021.50231.8322.42348.0049.23 sham171.3629.38245.1725.70354.2522.67 rtms176.0031.16238.5027.76348.2532.29face control subjects basal154.6018.48186.7318.80278.0034.07 sham160.7125.32185.3822.66289.0028.53 rtms146.539.05188.3839.55288.0038.95 migraine patients basal140.1843.27168.3659.79277.6425.03 sham166.8039.26186.6070.84287.5043.44 rtms161.2757.31209.9173.87309.0948.85the results of anova for sessions and for the interaction diagnosis session were not significantfig . 1mean values and standard deviations of laser pain rating measured by score of 0100 vas in control subjects ( n = 12 ) and migraine patients without aura ( n = 13 ) resulting from stimulation of the right hand and the right supraorbital zone in basal conditions and after sham tms and 5 hz rtms exposure at the left primary motor cortextable 2results of one - way anova with conditions basal , sham and rtms as factors ( df = 2 ) in migraine and control groupsvasn1 latencyn2 latencyp2 latencyn1 amplituden2 amplitudep2 amplituden2p2 amplitudemigraine patients ( n = 12 ) handf = 1.27f = 1.89f = 2.89f = 2.9f = 2.67f = 4.64 ( p = 0.032)f = 4.45 ( p = 0.035)f = 5.23 ( p = 0.023 ) facef = 3.32f = 1.78f = 1.78f = 1.78f = 2.98f = 4.34 ( p = 0.038)f = 4.88 ( p = 0.028)f = 6.53 ( p = 0.012)control subjects ( n = 11 ) handf = 2.12f = 1.56f = 1.89f = 1.29f = 0.089f = 4.16 ( p = 0.045)f = 4.05 ( p = 0.048)f = 4.14 ( p = 0.045 ) facef = 2.45f = 1.65f = 1.43f = 1.52f = 0.28f = 4 ( p = 0.049)f = 4.08 ( p = 0.048)f = 3.98 ( p = 0.049)the probabilities p for significant comparisons are reportedfig . 2mean values and standard deviations of laser - evoked potentials amplitudes for the right hand ( a ) and the right supraorbital zone ( b ) in 12 controls and 13 migraine patients without aura . subjects were evaluated in basal conditions , after sham tms and after 5 hz rtms exposure at the left primary motor cortex . results of multiple comparison bonferroni tests of the single groups : basal versus rtms : * p < 0.05 , * * p < 0.01 ; basal versus sham : p < 0.05 ; sham versus rtms : p < 0.05fig . 3laser - evoked potentials of a representative control subject ( female , 26 years old , right column ) and a migraine patient without aura ( female , 27 years old , left column ) obtained following laser stimulation of the dorsum of the right supraorbital zone ( upper panel ) and the right hand ( lower panel ) by laser at an intensity of 8 w and a duration of 25 ms in basal conditions and after sham tms and rtms of the left primary motor cortex . 4mean values and standard deviations of percent modification of n2p2 amplitude between the basal , sham and rtms conditions in migraine patients and controls . the results of student s t test , corrected for multiple comparisons , are shown : * p < 0.05 , * * p < 0.001 mean values standard deviations ( sd ) of laser - evoked potentials latencies ( lep ) , expressed in ms , in control subjects ( n = 12 ) and migraine patients ( n = 13 ) the results of anova for sessions and for the interaction diagnosis session were not significant mean values and standard deviations of laser pain rating measured by score of 0100 vas in control subjects ( n = 12 ) and migraine patients without aura ( n = 13 ) resulting from stimulation of the right hand and the right supraorbital zone in basal conditions and after sham tms and 5 hz rtms exposure at the left primary motor cortex results of one - way anova with conditions basal , sham and rtms as factors ( df = 2 ) in migraine and control groups the probabilities p for significant comparisons are reported mean values and standard deviations of laser - evoked potentials amplitudes for the right hand ( a ) and the right supraorbital zone ( b ) in 12 controls and 13 migraine patients without aura . subjects were evaluated in basal conditions , after sham tms and after 5 hz rtms exposure at the left primary motor cortex . results of multiple comparison bonferroni tests of the single groups : basal versus rtms : * p < 0.05 , * * p < 0.01 ; basal versus sham : p < 0.05 ; sham versus rtms : p < 0.05 laser - evoked potentials of a representative control subject ( female , 26 years old , right column ) and a migraine patient without aura ( female , 27 years old , left column ) obtained following laser stimulation of the dorsum of the right supraorbital zone ( upper panel ) and the right hand ( lower panel ) by laser at an intensity of 8 w and a duration of 25 ms in basal conditions and after sham tms and rtms of the left primary motor cortex . each trace represents the average of 20 artifact - free responses mean values and standard deviations of percent modification of n2p2 amplitude between the basal , sham and rtms conditions in migraine patients and controls . the results of student s t test , corrected for multiple comparisons , are shown : * p < 0.05 , * * p < 0.001 the n2 and p2 amplitudes were also separately considered to examine the effects of sham and rtms on the control and migraine groups , showing the same trend as the whole n2p2 complex ( table 2 ) . the bonferroni test showed that in the control group , the p2 and the n2 obtained by the hand and the face stimulation were both reduced in rtms condition , with respect to the basal situation ( hand : n2 p = 0.049 ; p2 p = 0.043 ; face : n2 p = 0.49 ; p2 0.043 ) , as well as in the migraine group ( hand : n2 p = 0.03 ; p2 p = 0.034 ; face : n2 p = 0.024 ; p2 p = 0.022 ) , where a significant effect of the sham rtms was confirmed , with respect to real rtms ( hand : n2 p = 0.043 ; p2 p = 0.048 ; face : n2 p = 0.039 , p2 p = 0.035 ) and basal condition ( hand : n2 p = 0.03 ; p2 0.032 ; face : n2 p = 0.036 ; p2 p = 0.032 ) . this is the first study that has attempted to confirm the efficacy of motor cortex stimulation in reducing cortical responses to painful stimuli in migraine patients . hf rtms of the motor cortex has been suggested for the treatment of other pain - related diseases since the initial report by lefaucheur in 2001 . the main results of our findings are that ( 1 ) sham and rtms did not have a substantial effect on laser pain in patients and controls ; ( 2 ) both sham and rtms do not affect the n1 wave in either control or migraine group ; ( 3 ) sham rtms has a placebo effect on the vertex lep amplitude in migraine patients ; and ( 4 ) rtms has an effect on the later lep amplitudes in both control and migraine groups , with a more pronounced effect in the migraine patients . in regard to point ( 1 ) , laser pain was not significantly modified by motor cortex stimulation in normal subjects or migraine patients , despite a significant reduction of the evoked responses recorded from the vertex . similarly , in a study on acute therapies for migraine attack , we observed no drug - induced effects on laser pain concomitant with the clear inhibition of laser - evoked responses . this apparent contrast may be supported by the principle that leps reflect more the status of sensory pathways than the perception of subjective pain , despite a linear correlation between the intensity of pain perception and the amplitude of vertex leps is often present . there are also evidences supporting a reducing effect of drugs with opioid activity ( e.g. tramadol ) , on leps amplitude , without affecting laser pain perception . coming to the point ( 2 ) , the m1 repetitive magnetic stimulation seemed to affect the lep components differently , as the early temporal n1 component was substantially unmodified despite the slight reduction induced by the sham and the real stimulation procedure in migraine patients at the hand level . although the small amplitude of n1 restricts its clinical use , the bipolar montage linking temporal and midline electrodes employed in this study generally renders it sizeable enough for detecting possible changes across different conditions , including changes in migraine patients . eeg / meg dipole analysis and intracortical recordings indicate that the n1 signal is mainly generated in the upper bank of the sylvian fissure , encompassing the secondary somatosensory area ( sii ) and the posterior insula [ 2831 ] . the present results may thus suggest that these cortical areas are not conditioned by the stimulation of the motor cortex , either in normal subjects or in migraine patients , in accordance with previous findings about the effects of voluntary movement on leps . furthermore , the n1 is less sensitive to attention and vigilance compared to the vertex complex , which may also explain the lack of a placebo effect in this component . regarding the point ( 3 ) , at the hand and trigeminal levels , a significant amplitude reduction was observed in the vertex leps of the migraine patients during the sham session , suggesting that the tms procedure has a strong placebo influence . in the control group , this placebo effect was present at the hand level but was not significant , and it was absent at the trigeminal level . dipole modeling of scalp eeg signals and intracranial recordings suggests that the vertex lep complex results from the simultaneous activity of several cortical generators , with major participation of the anterior cingulate cortex ( acc ) and variable contribution from the insular and/or frontal operculum . its amplitude is especially sensitive to changes in attention and arousal levels and also to the placebo effect , which mainly affects the p2 wave . in our experiment , a separate analysis of the negative positive components of the vertex complex did not show that n2 and p2 amplitudes behaved differently , suggesting that cortical areas devoted to both cognitive and emotive aspects of pain are inhibited by sham stimulation . we can assume that the placebo effect may prevail in patients compared to normal subjects , as patients will hope for a positive effect to alleviate their suffering . in addition , the placebo effect observed in the leps following stimulation of the trigeminal site in migraine patients and not in controls may be due to the different motivation and emotive involvement linked with the headache site . on the other hand , one could speculate that the inefficacy of a sham rtms at the trigeminal zone in controls may be caused by the somatotopy of placebo effect , such as that suggested by benedetti et al . . the modulation of nociceptive processing has peculiar aspects in migraine patients , as it is less evident under distraction in cognitive tasks and is normally induced under distraction by affective images [ 27 , 35 ] . the sham tms procedure induced a placebo effect on nociceptive processing in migraine patients , without an evident effect on subjective pain rating . this apparent discrepancy was interpreted by wager et al . as a separate effect of placebo on early nociceptive processing , as shown by the p2 inhibition , and later processing of evaluation or cognitive judgment leading to the reduction of the pain rating . similarly , colloca et al . observed a reduction in the n2p2 amplitude in the absence of a reduction in the laser pain rating in a cohort of normal subjects subjected to the placebo effect by verbal suggestion . finally ( point 4 ) , we observed that hf tms of the primary motor cortex induced a significant reduction in the vertex lep amplitudes in migraine patients at both sites ( hand and trigeminal ) , compared to basal and sham conditions . in contrast , hf tms did not differ significantly from shams tms in controls at the hand level . compared to the basal sessions , a slight latency increase of about 30 ms was also detected in rtms - treated migraine patients in the n2 and p2 components , but this difference did not reach statistical significance and needs to be confirmed using a larger data set . our results suggest that the interaction between the motor and nociceptive cortex predominantly involves the cortical areas subtending the vertex leps , in accordance with a functional relationship between m1 and acc [ 3739 ] . the effect of rtms was similar for the negative and positive compounds of the vertex complex . similarly , in a study by le pera et al . , the preparation of voluntary movement inhibited the vertex lep amplitude , leaving the temporal n1 unchanged . in the study by le pera et al . , the inhibitory effect on the nociceptive system induced by physiological activation of the motor cortex involved only cerebral pain processing at the body site corresponding to the physiologically activated motor cortex . in our study , rtms modulation of m1 realized on the area innervating the hand also reduced pain - related responses at the trigeminal level , suggesting that the inhibition of the nociceptive cortex is not dependent upon the somatotopic relationship between the stimulated m1 zone and the zone experiencing pain , as suggested by lefaucheur et al . . the effect of rtms appeared to be more constant across the two evaluated sites in the migraine group than in the control group , which lacked significant late lep reduction at the hand level following rtms compared to the sham procedure . according to curra et al . , a deficit in cortical inhibitory interneurons may affect the motor cortex in migraine patients , as well as in chronic neuropathic pain . restoration of gabaergic neurotransmission in the motor cortex induced by hf tms may have an analgesic effect . this hypothesis was recently confirmed by the same authors , who demonstrated a significant reduction in vertex leps and laser pain in a cohort of patients with chronic neuropathic pain . the effects of hf tms may be more evident when the motor cortex excitability is changed due to chronic pain . in line with this theory , one might predict better results in chronic migraine patients , whose vertex leps are scarcely modified by cognitive distraction . in summary , the state of the motor cortex in migraine patients could explain the more evident modulation of late leps induced by hf rtms with respect to controls . strong caution should be used in extending the validity of these findings to clinical practice . the study design was not suitable to evaluate clinical changes in our migraine patients , given that multiple consecutive sessions of rtms are suggested to improve chronic pain and specifically chronic migraine , and that the sham and rtms procedures were applied in two consecutive days in the same patient . in addition , in migraine group , the leps were affected by a strong placebo effect , which is a well - known phenomenon in previous experiments exploring the efficacy of therapeutic procedures . moreover , the real rtms exerted a considerable reduction of vertex leps in comparison with the sham , especially at trigeminal level . presently , we can suggest that hf rtms of motor cortex influenced nociceptive cortical responses better than other modalities of pain modulation [ 18 , 27 ] , also supported by a strong placebo effect , which potential advantage should not be ignored .

the aim of this study was to examine the effects of high - frequency ( hf ) repetitive transcranial magnetic stimulation ( rtms ) of the left primary motor cortex ( m1 ) on subjective pain and evoked responses induced by laser stimulation ( leps ) of the contralateral hand and supraorbital zone in a cohort of migraine patients without aura during the inter - critical phase , and to compare the effects with those of non - migraine healthy controls . thirteen migraine patients and 12 sex- and age - matched controls were evaluated . each rtms session consisted of 1,800 stimuli at a frequency of 5 hz and 90% motor threshold intensity . sham ( control ) rtms was performed at the same stimulation position . the vertex lep amplitude was reduced at the trigeminal and hand levels in the sham - placebo condition and after rtms to a greater extent in the migraine patients than in healthy controls , while the laser pain rating was unaffected . these results suggest that hf rtms of motor cortex and the sham procedure can both modulate pain - related evoked responses in migraine patients .

ampicillin is an important semisynthetic -lactam antibiotic and it is still widely used nowadays because of its good efficacy in urinary tract infections , respiratory infections , and other diseases caused by germs and bacteria . in recent years , the requirement of quality control for related substances in chemicals became stricter no matter in structure confirmation or content limitation . ampicillin was especially degradable in presence of aqueous solution or humid storage environment , which would lead to the formation of a variety of degradation products . these related substances ( the related substances previously reported were shown in table 1 ) would have a great influence on the quality of the products and clinical medication safety . although there has been much research on the related substances of ampicillin [ 2 , 3 ] , it is not completely explicit so far . to ensure the clinical safety and meet the new requirement of related substances in chemicals , it is still necessary to conduct further studies to develop a rapid and efficient method to describe in more detail the related substances of ampicillin capsule . many analytical methods including high - performance liquid chromatography ( hplc ) [ 1 , 5 ] , high - performance capillary electrophoresis ( hpce ) , high - performance liquid chromatography - atmospheric pressure chemical ionization mass ( hplc - apci - ms ) , and high - performance liquid chromatography - electrospray mass spectrometry ( hplc - esi - ms ) [ 8 , 9 ] had been utilized for the analysis of ampicillin . among these methods , lc - esi - ms had been shown to be a powerful technique for the analysis of ampicillin and its related substances due to its excellent ability in separation and identification . in this paper , a simple , rapid , and sensitive rapid resolution liquid chromatography coupled with electrospray ionization tandem mass spectrometry ( rrlc - esi - ms ) method was established for the identification of the related substances in ampicillin capsule . the result suggested that this technique could facilitate rapid and accurate identification of related substances in ampicillin capsule . methanol ( hplc grade ) was purchased from fisher scientific ( pittsburgh , pa , usa ) . formic acid ( hplc grade ) deionized water was further purified with a milli - q water system ( bedford , massachusetts , usa ) . the chromatographic separation was performed with an agilent 1200 series rapid resolution liquid chromatography system ( agilent technologies , usa ) , equipped with a binary pump , a microvacuum degasser , a high - performance autosampler , a column compartment , a diode array detector , and a ms detector . the samples were separated on a 1.8 m agilent zorbax xdb - c18 column ( 50 mm 4.6 mm ) at a flow rate of 0.4 mlmin . the mobile phases consisted of 0.1% formic acid solution ( a ) and methanol ( b ) . the optimized rrlc elution conditions were as follows : 02 min , 10% b ; 210 min , 1020% b ; 1020 min , 2050% b ; 2025 min , 50% b ; 25 - 25.1 min , 5010% b ; 25.130 min , 10% b. dad spectra were acquired over a scan range of 190400 nm . agilent 6320 mass spectrometer with an agilent chemstation to control and process the data was performed with the esi source in positive ion mode . the vaporizer temperature was maintained at 300c . the flow rate of the drying gas and the pressure of the nebulizing gas were set at 12 lmin and 35 psi , respectively . the capillary voltage was kept at 3.5 10 v. the mass spectrometer scanned from a mass - to - charge ratio ( m / z ) 100900 . the contents of ampicillin capsule ( equivalent to 10 mg ampicillin ) were dissolved in 10 ml methanol and then filtered through a 0.22 m syringe filter . and an aliquot ( 1 l ) of the filtrate was subjected to rrlc - esi - ms for analysis . it was necessary to study the characterization of the mass spectra of the parent drug to identify the molecular structure of the related substances in ampicillin capsule . identifications were based on the fact that the related substances of ampicillin usually contain structural fragments and analogous cleavage characteristic of the parent drug . structural information and fragmentation mechanisms had been deduced from ions in the mass and collision spectra . this knowledge was useful in the analysis and identification of related substances in ampicillin capsule . we utilized knowledge of characteristic fragment ions of ampicillin and its related substances to identify their structures . figures 1 and 2 showed the detailed total ion chromatography ( tic ) and mass spectrum of ampicillin and its related substances , respectively . ampicillin yielded an abundant ion in the esi mass spectrum at m / z 350.1 . the esi mass spectrum of this ion ( m / z 350.1 ) was shown in figure 2 . the fragment ions at m / z 106.2 and 160.0 were reported to arise from the benzylamine group and the thiazolidine ring . the fragment ion at m / z 192.0 was proposed to arise as a result of losing a nh2 group at the benzylamine side chain followed by an oxygen rearrangement and cleavage of the -lactam ring . the fragment ion at m / z 174.0 could be attributed to the loss of h2o from the fragment at m / z 192.0 , but it might arise from other pathways . this part of the investigation focused on the characterization of the esi - ms properties of the parent drug and its known related substances . table 2 showed the chromatographic and mass spectral characteristics of the detected related substances in ampicillin capsule . all of them produced protonated quasimolecular ion at m / z 368.1 [ m + h ] , major ions at m / z 324.1 , 307.1 , 279.2 , and 175.1 in esi mode . based on diagnostic ions ( m / z 324.1 , 307.1 , and 175.1 ) and comparison with the published literature of known related substances of ampicillin , peak 1 and peak 2 were identified as isomers of ampicilloic acid . ( 5s , 6r ) or ( 5r , 6r ) ampicilloic acids were the two groups of ampicilloic acid isomers which were reported to be the metabolites and degradation products of ampicillin . according to the retention behavior in reversed - phase chromatography of peak 1 and peak 2 and the related literature , peak 1 and peak 2 were tentatively identified as ( 5s , 6r ) ampicilloic acid and ( 5r , 6r ) figure 4 showed the proposed ms fragmentation pathway for the fragmentation ions of ampicilloic acid . peak 3 produced a protonated molecular ion at m / z 350.1 [ m + h ] , fragment ions at m / z 333.0 [ m nh3 ] , 192.0 , 174.0 , 160.0 , and 106.1 in esi mode . peak 5 was clearly identified as ampicillin based on comparison of its retention time and mass spectrometric data with reference standards . peak 3 showed the same fragment ions , fragmentation pattern , and characteristic ions as peak 5 . considering that peak 3 had a much shorter retention time than peak 5 , and with the comparison of related substances reported in the literature , peak 3 was tentatively identified as l - ampicillin . figure 5 showed the proposed ms fragmentation pathway for the fragmentation ions of l - ampicillin . peak 4 gave a protonated molecular ion [ m + h ] with an m / z value of 324.1 , major fragment ions at m / z 307.0 , 279.1 , 201.0 , 175.0 , 147.1 , 128.1 , and 106.1 in esi mode . peak 4 was tentatively identified as ( 5r ) or ( 5s ) ampilloic acid based on its characteristic ions ( m / z 324.1 , 307.0 , 279.1 , 128.1 , and 106.1 ) and comparison with the published literature of known related substances of ampicillin . peak 6 produced major fragment ions at m / z 364.1 [ m + k + h ] , 191.9 , 174.0 , 128.0 , and 106.2 . they all had similar ms fragmentation patterns ( m / z 191.9 , 174.0 , 128.0 , and 106.2 ) . by comparison with the published literature , peak 6 was tentatively identified as ( 5r ) or ( 5s ) ampilloic acid . ( 5s ) or ( 5r ) ampilloic acids were the isomers of ampilloic acids which were reported to be metabolites or degradation products of ampicillin . however , the exact structure of these two components could not be determined due to the limited information . figure 6 showed the proposed ms fragmentation pathway for the fragmentation ions of ampilloic acids . peak 7 had a molecular weight of 350 ( [ m + meoh + h ] , m / z 382.1 ) and five major fragment ions were observed at m / z 331.1 , 223.0 [ 191 + meoh ] , 206.0 [ 174 + meoh ] , 160.0 , and 106.2 . as it was reported , the two characteristic fragment ions m / z 160.0 and 106.2 were the representative fragment ions of ampicillin . by comparison with the published literature , figure 7 showed the proposed ms fragmentation pathway for the fragmentation ion of diketopiperazines of ampicillin . peak 10 produced a protonated molecular ion at m / z 483.1 [ m + h ] , the major fragment ions at m / z 439.1 , 350.0 , 267.0 , and 239.1 in esi mode . fragment ion at m / z 439.1 could be attributed to loss of one cooh from the ion ( m / z 483.1 ) . based on the mass spectra , peak 10 was identified as d - phenylglycylampicillin [ 1 , 11 ] . figure 8 showed the proposed ms fragmentation pathway for the fragmentation ion of d - phenylglycylampicillin . peak 15 had a molecular weight of m / z 699.1 [ m + h ] and three major fragment ions m / z 540.1 , 381.1 , and 248.0 in esi mode . upon collision - induced dissociation ( cid ) , the ion at m / z 699.1 eliminated one molecule of thiazolidine ring to produce m / z 540.1 . the m / z 540.1 ion could further lose one molecule of thiazolidine ring successively to give significant m / z 381.1 fragment ion . thus , peak 15 was identified as closed - cycle dimer based on the published literature . closed - cycle dimer was the main cause of allergy , so that we must control the amount of this related substance in ampicillin capsule . peak 16 produced major fragment molecular ions at m / z 524.8 [ m + h ] , 889.3 , 730.3 , 571.2 , and 160.0 in esi mode . upon cid , the ion at m / z 1048 [ m ] eliminated one molecule of thiazolidine ring to produce m / z 889.3 . the m / z 889.3 ion could lose one molecule of thiazolidine ring successively to give significant m / z 730.3 ion . the m / z 730.3 ion could further lose one molecule of thiazolidine ring successively to give significant m / z 571.2 . thus , peak 16 was identified as closed - cycle trimer based on the published literature . closed - cycle trimer was also the main cause of allergy , so that we must control the amount of this related substance in ampicillin capsule . this part of the investigation was to identify the chemical structures of unknown related substances which were not yet reported in ampicillin capsule based on the mass fragment characterization and cleavage pathways of ampicillin and its known related substances . by means of the rrlc - esi - ms experiments , in this part , chemical structures of four related substances were tentatively identified in ampicillin capsule for the first time . table 3 showed the chromatographic and mass spectral characteristics of the above unknown related substances detected by rrlc - esi - ms in ampicillin capsule . peak 9 had a molecular weight of m / z 566.1 [ m + h ] and three major fragment ions m / z 407.1 , 248.1 , and 191.0 in esi mode . the fragment ions at m / z 407.1 and 248.1 eliminated one molecule of thiazolidine ring successively from ion at m / z 566.1 [ m + 1 ] . the fragment ion at m / z 191.0 probably should be a characteristic fragment ion of ampicillin piperazine-2,5-dione . thus , peak 9 was identified tentatively as ampicilloic acid and 6-aminopenicillanic acid ( 6-apa ) oligomer . figure 9 showed the proposed ms fragmentation pathway for the fragmentation ion of ampicilloic acid and 6-apa oligomer . peak 12 produced a protonated molecular ion at m / z 548.1 [ m + h ] and three major fragment ions at 443.1 , 358.1 , and 199.0 . based on fragment ions , peak 12 was tentatively identified as 6-apa ampicillin amide . figure 10 showed the proposed ms fragmentation pathway for the fragmentation ion of 6-apa ampicillin amide . peak 13 had a molecular weight of 673.2 [ m + h ] and four major fragment ions m / z 655.1 , 514.1 , 324.1 , and 191.0 . the fragment ions at m / z 655.1 and 514.1 were attributed to the loss of one water molecule ( 18 da ) and one molecule of thiazolidine ring from ion at m / z 673.2 . the fragment ion at m / z 191.0 was the fragment ion of ampicilloic acids . figure 11 showed the proposed ms fragmentation pathway for the fragmentation ion of ampilloic acids and ampicilloic acids oligomer . peak 14 produced a protonated molecular ion at m / z 483.1 [ m + h ] , which was identified as the other isomer of d - phenylglycylampicillin because peak 14 and peak 10 both showed the same diagnostic ions at m / z 439.1 , 350.1 , 239.1 , and 160.0 . the rrlc - esi - ms technique was successfully established to rapidly determine and identify the structures of the related substances in ampicillin capsule . rrlc is efficient in separating chemical compounds in a mixture , and ms provides abundant information for structural elucidation of the compounds when tandem mass spectrometry is applied . although ampilloic acids , ampicilloic acid , and closed - cycle dimer had been investigated previously by lc - ms method , ms information and characteristic diagnostic ions of a number of components in ampicillin capsule were described simultaneously for the first time . none of the previously reported methods have led to so much chemical information on the related substances in ampicillin capsule . the results of this study had identified 13 out of 15 related substances in ampicillin capsule . unfortunately , three groups of isomers ( peak 1 and peak 2 , peak 4 and peak 6 , and peak 10 and peak 14 ) and condensation of amino and carboxyl groups ( peak 9 , peak 12 , and peak 13 ) could not be identified fully by current rrlc - esi - ms information . peak 8 and peak 11 had not yet been identified based on current mass spectra information . in summary , this investigation had provided an example of the rapid identification of related substances in ampicillin capsule . the meaningful information for the related substances in ampicillin capsule could lead to the development of the understanding of the quality and safety of the drug .

rapid resolution liquid chromatography coupled with electrospray ionization tandem mass spectrometry ( rrlc - esi - msn ) was used to separate and identify related substances in ampicillin capsule . the fragmentation behaviors of related substances were used to identify their chemical structures . finally , a total of 13 related substances in ampicillin capsule were identified , including four identified components for the first time and three groups of isomers on the basis of the exact mass , fragmentation behaviors , retention time , and chemical structures in the literature . this study avoided time - consuming and complex chemosynthesis of related substances of ampicillin and the results could be useful for the quality control of ampicillin capsule to guarantee its safety in clinic . in the meantime , it provided a good example for the rapid identification of chemical structures of related substances of drugs .

the pore and cnbd sequences of the plant cyclic nucleotide - gated channels differ from the pore and cnbds in other plant ion channel families . phylogenies based on alignments of the pore , cnbd , or full - length cngc sequences are similar , showing that the evolution of these functional domains preceded the expansion of plant cngc genes that occurred after the split between green algae and higher plants , and that the split between dicots and monocots occurred after the advent of the higher plant cngcs . an alignment of just this motif region from the cngcs produces a cladogram that is almost identical to published phylogenies of the full - length sequences . this motif may therefore be used to refine tentative annotations and to find novel cngcs in newly sequenced plant genomes . whether this motif represents differences in the function or regulation of plant cngcs has yet to be evaluated . the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .

ligand - gated cation channels are a frequent component of signaling cascades in eukaryotes . eukaryotes contain numerous diverse gene families encoding ion channels , some of which are shared and some of which are unique to particular kingdoms . among the many different types are cyclic nucleotide - gated channels ( cngcs ) . cngcs are cation channels with varying degrees of ion conduction selectivity . they are implicated in numerous signaling pathways and permit diffusion of divalent and monovalent cations , including ca2 + and k+ . cngcs are present in both plant and animal cells , typically in the plasma membrane ; recent studies have also documented their presence in prokaryotes . all eukaryote cngc polypeptides have a cyclic nucleotide - binding domain and a calmodulin binding domain as well as a six transmembrane / one pore tertiary structure . this review summarizes existing knowledge about the functional domains present in these cation - conducting channels , and considers the evidence indicating that plant and animal cngcs evolved separately . additionally , an amino acid motif that is only found in the phosphate binding cassette and hinge regions of plant cngcs , and is present in all experimentally confirmed cngcs but no other channels was identified . this cngc - specific amino acid motif provides an additional diagnostic tool to identify plant cngcs , and can increase confidence in the annotation of open reading frames in newly sequenced genomes as putative cngcs . conversely , the absence of the motif in some plant sequences currently identified as probable cngcs may suggest that they are misannotated or protein fragments .

pixelized photon detector ( ppd ) , a generic name of multi - pixel geiger - mode avalanche photodiodes , is a high - sensitivity photon detector developed recently . this device has attracted much attention since a ppd has great advantages over photo - multipliers , such as insensitivity to magnetic fields , compactness , low bias voltage and low power consumption , although the active area of the device is limited to be @xmath5 mm@xmath1 at present . therefore a ppd device is very useful for high - energy and astrophysics experiments and medical science applications , especially for a readout device with scintillating fibers , wave length shifting fibers , and fine granulated scintillating crystals , etc . a review about ppd has been prepared by d. renker @xcite , for example . the multi - pixel photon counter ( mppc ) is one of such ppd devices which has been developed by hamamatsu photonics @xcite . three types of mppcs ( 100 , 400 , and 1600-pixels type ) with an active area of 1@xmath61 mm@xmath1 , and some other larger devices , are commercially available at present . experimental groups , such as t2k , ilc , belle , trek and koto , are planning to adopt the mppc in their detector systems for scintillating fibers and/or wavelength - shifting fibers readout , and for ring imaging cherenkov detectors @xcite . experimental studies of the basic performance of the mppc have been carried out by those groups ( see e.g. @xcite ) . for practical use of the mppc , radiation hardness is one of the important issues to be made clear for applications in a high radiation environment . in general , an indication of radiation damage on silicon devices is an increase of the leakage current , which is caused by lattice defects created due to radiation damage . an experimental study with a positron beam has been reported for radiation hardness of old types of mppcs , showing an increase of the leakage current and the dark - count rates but no significant change in the gain and the photon - detection efficiency @xcite . for @xmath7-ray irradiation , high dark pulses generated at the outer regions of individual pixels have been observed after 240 gy irradiation in addition to increases of the leakage current and the noise rates @xcite . to investigate hadron - induced radiation damage , which is important in high - energy physics experiments , we performed an irradiation experiment with a 53.3 mev proton beam . in the following part of this report , at first , we describe the setup and the procedure for the irradiation experiment . then , characteristic changes , such as the leakage current , gains , dark counts , pulse - height distributions , are presented . finally , we discuss issues to be concerned with the effects caused by proton - induced radiation damage from a practical standpoint . two pieces of mppc samples , hamamatsu s10362 - 11 - 050c delivered in february 2007 , were irradiated with a proton beam in the experiment . we refer to these samples as `` sample # 1 '' and `` sample # 2 '' . the samples have an active area of @xmath8 mm@xmath1 and consist of 400 pixels of geiger - mode avalanche photodiodes whose individual pixel - size is 50@xmath650 @xmath9m@xmath1 . the operating voltage , which is the voltage giving a gain of 7.5@xmath610@xmath10 at 25 @xmath11c , is 69.75 v for sample # 1 , and 69.58 v for sample # 2 , respectively . mm@xmath1 hole around the sample to avoid radio - activation . a voltage source was connected to the connector b@xmath12 to apply a negative reverse voltage to the sample . signals from the sample were read out from the connector s@xmath13 . capacitances ( c@xmath14:0.047 @xmath9f , c@xmath15:0.1 @xmath9f ) and resistors ( r@xmath14:10 k@xmath16 , r@xmath15:1 k@xmath16 ) were used for noise - filter circuits . a blue led mounted on the substrate was employed as a light source for measurement of pulse - height distributions.,width=264 ] one of the mppc samples was mounted on a print substrate as illustrated in fig . [ fig : substrate ] . protons were directed onto the sample from the direction perpendicular to the entrance face of the sample . to avoid radio - activation of materials other than mppc caused by proton irradiation , a 20@xmath625 mm@xmath1 hole was made in the substrate . a blue led ( nichia nspb320bs , @xmath17 nm ) on the substrate was used as a light source for measurements of pulse - height distributions . a voltage source , keithley model 2400 , was employed in order to apply a negative reverse voltage to the mppc sample . the leakage current of the sample was measured with the voltage source and recorded by the laptop computer connected to the voltage source via gp - ib communications . signals from the mppc sample were sent to a readout circuit , consisting of nim and camac modules , to measure pulse - height spectra and dark - noise rates . the resistors and capacitors on the substrate were used as noise - filter circuits . the experiment was carried out at the research center for nuclear physics , osaka university by using the 53.3 mev proton beam from the avf cyclotron . protons were extracted from a vacuum beam pipe of the h - course beamline through a thin aluminum window to the experimental area . the beam size was set to be a rectangular shape of 6@xmath68 mm@xmath1 by adjusting the several beamline slits , which was enough to cover the active area of mppc , 1@xmath61 mm@xmath1 . the beam current was first tuned to be 2 na at the beam stopper placed downstream of the final slit . then the beam intensity was further reduced and controlled by inserting several mesh - type attenuators in the beamline located between the ion source and avf cyclotron , so that the proper proton beam flux was obtained for the irradiation experiment ( 10@xmath18 - 10@xmath10 p / mm / s ) . the uniformity of the beam intensity near the beam center was measured with a copper collimator and plastic scintillators . from this measurement , we confirmed that the position dependence of the beam intensity varied by less than 5% in the region of 4@xmath64 mm@xmath1 around the beam center . [ fig : setup ] shows the experimental setup for this proton irradiation . a mppc sample mounted on the substrate was placed just after the vacuum window of the beam pipe . the sample was covered with a black sheet ( 200 @xmath9 m thickness ) for light shielding . we set a platinum thermometer near the mppc sample in order to monitor variations of the temperature inside of the black sheet during the experiment . the proton beam emerging from the beam pipe passed through the mppc sample , and then it was trimmed with a copper collimator to be 3.5 mm@xmath19 . two plastic scintillators placed downstream of the collimator were used to monitor the number of protons contained in the collimated beam . the proton beam was dumped in the beam stopper placed at the end of the beamline . the intensity of the beam impinging on the active area of the mppc sample was estimated from the total counts of the coincidence signals of the plastic scintillators and the measurement times . since the beam intensity was almost flat in the region of 4@xmath64 mm@xmath1 around the beam center , we obtained the intensity from the coincidence rate by taking the ratio between the active area of the mppc sample and the area of the collimator hole , @xmath20 , into account , where we assumed the machining accuracy of the collimator hole to be 50 @xmath9 m . the following corrections were also taken into account : beam loss due to the scattering at the ceramic package of the mppc sample and the black sheet ( @xmath21 ) , and the beam divergence induced difference of the beam density at the sample position and at the collimator position ( @xmath22 ) . the factor @xmath21 was obtained by the coincidence rate change between with and without the mppc sample wrapped by the black sheet . @xmath22 was also determined by comparing the coincidence rates at different collimator positions . we estimated @xmath21 and @xmath22 to be 2.71 and 1.18 , respectively . the considered uncertainties of the product of @xmath23 are the coincidence rate fluctuation during the irradiation ( 3.4 % ) and accuracy of the detector and collimator positioning ( 0.9 % ) . as the result , we obtained the correction factor , @xmath24 , to multiply to the coincidence rates . the proton beam - flux during irradiation was monitored in this way . a readout circuit consisting of nim and camac modules was prepared for the measurements of pulse - height distributions and dark - noise rates of the mppcs as illustrated in fig . [ fig : circuit ] . the blue led was driven with ttl signals coming from a 100 hz clock generator . signals from the mppc sample were sent to an amplifier ( phillips model 777 ) where the gain was set to be 56.4 . then , these signals were integrated with a 12-bit charge - sensitive adc of a camac module ( repic rpc-022 ) . gate signals from the clock generator were input to the adc module . the gate width , 55 ns , was determined so that entire pulse signals coming from the mppc were integrated , where the typical fall time of the signals was 40 ns . the intensity of the led light was adjusted in such a way that the average number of photo - electrons ( @xmath9 ) was about 1.3 . this value can be calculated from the null probability of the poisson statistics @xmath25 @xmath26 ) , which was obtained from the ratio of the number of pedestal events to the total events in an adc distribution . a discriminator ( phillips model 705 ) and a visual scaler ( kaizu works kn1860 ) were used for the measurement of dark - noise rates . sample # 1 + [ cols="^,^,^,^,^,^,^",options="header " , ] first , we checked basic performance of the mppc samples , such as gain , current - voltage ( @xmath27-@xmath28 ) curve and noise rate , before the proton irradiation . this performance is to be compared with that after the irradiation . for the next step , one of the mppc samples with normal operating voltage was irradiated with the proton beam . after the irradiation , in order to check recovery effects on radiation damage , the leakage current was monitored for about 1 hour under the condition without the beam . then we measured the basic performances after the irradiation . this process was repeated several times . we used two different beam intensities for the irradiation . one of the mppc samples , sample # 1 , was irradiated with a proton beam flux ( @xmath29 ) of @xmath30 p / mm@xmath1/s . the second mppc , sample # 2 , was irradiated with a lower flux , @xmath31 p / mm@xmath1/s . one irradiation took 10 minutes for both the samples . for sample # 1 , we repeated the proton irradiation twice , thereby estimated the proton fluence ( @xmath32 ) is @xmath33 p / mm@xmath1 in total . on the other hand , three times irradiation were made for sample # 2 , thus the total fluence is @xmath34 p / mm@xmath1 . the beam flux and total fluence in each irradiation are summarized in table [ tab : flux ] . instead of the proton fluence @xmath32 , it may be useful to represent a total fluence with 1 mev neutron equivalent fluence ( @xmath2 ) . this quantity is commonly used in order to evaluate damage levels caused by different radiation sources and different energies based on the niel scaling hypothesis , which is the assumption that damage level in silicon bulk is related to the cross - section of processes with non - ionization energy loss @xcite . the @xmath2 can be obtained with a hardness factor @xmath35 as @xmath36 , where the value of the @xmath35 for 53.3 mev protons is about 1.7 obtained from the displacement damage function described in the reference @xcite . hence , we estimated the @xmath2 for sample # 1 to be @xmath37 n / mm@xmath1 , and @xmath38 n / mm@xmath1 for sample # 2 , respectively . the absorption dose ( @xmath39 ) due to the proton irradiation can be estimated from the proton fluence @xmath32 by taking the mass stopping power of 53.3 mev protons in silicon , @xmath40 mev@xmath41cm@xmath1/g , into account . the estimated dose rates for both sample # 1 and sample # 2 were 130 gy / h and 16 gy / h , respectively . thus , the total radiation dose was 42 gy for sample # 1 , and 8.0 gy for sample # 2 . the temperature in the experimental area was controlled to be stable . during the experiment the temperature near the mppc samples ( @xmath43 ) was in the range 27.0 - 28.0 @xmath11c . note that we estimated the maximum temperature increment caused by the proton beam in the mppc volume to be 0.03 @xmath11c in the case of 10 minutes irradiation , which was calculated from the beam energy deposition in the mppc and the specific heats of the device materials . thus , we concluded that the temperature increase due to the irradiation was negligible compared with the temperature fluctuation in the experimental area . the temperatures in each measurement are also summarized in table [ tab : flux ] . [ fig : it](a ) shows the variations of the leakage current of sample # 1 during the experiment . the measurement of the leakage current was started 10 minutes before the first irradiation , where the leakage current was about @xmath44 @xmath9a at the operating voltage . we irradiated the sample with the proton beam for 10 minutes ( see the leftmost hatched region in the figure ) . during the first irradiation , the current almost linearly increased with time due to radiation damage . step - like changes at the beginning and ending of the irradiation , @xmath451.0 @xmath9a , would be caused by free carriers generated due to the ionizing processes of the beam protons traversing in silicon . after the beam stops , the leakage current gradually decreased with time . this indicates recovery phenomenon from the radiation damage , although the recovery was not completed to the original condition within hours . the second irradiation was performed after the measurements of pulse - height distributions , @xmath27-@xmath28 curves and dark noise . again the leakage current increased linearly with time , and a similar recovery effect is also seen in the second irradiation . note that we applied the fixed operating voltage with the voltage source during the measurement ; thus , the increase of the leakage current due to the radiation damage caused a gain reduction due to a voltage drop at the resistors @xmath46 and @xmath47 in the filter circuit ( see fig . [ fig : substrate ] ) . such effect should be corrected for performance studies and this will be discussed later . the result of leakage - current variations for sample # 2 , which was irradiated with a lower beam flux , is shown in fig . [ fig : it](b ) . although the increasing rate during the irradiation was low compared to that for the sample # 1 irradiation because of the lower beam flux , we have found a similar tendency as in the sample # 1 irradiation , that is , the linear increase of the leakage current and the recovery effect . the offset of the leakage current due to the ionizing processes of protons in silicon was about 0.3 @xmath9a in this case . as we mentioned , the effect of the voltage drop at the resistors @xmath46 and @xmath47 should be corrected . since the leakage current ( @xmath48 ) flows the resistors arranged in series , the voltage drop is expressed as @xmath49 . hence , actual reverse voltages of the mppc ( @xmath50 ) is given by @xmath51 where @xmath52 denotes the voltage applied by the voltage source . in the following part of this paper , we will express reverse voltages as @xmath50 in place of @xmath52 . [ fig : i - flux ] shows the leakage current of both samples under the operating voltages ( @xmath53 for sample # 1 and @xmath54 for sample # 2 ) as a function of the 1 mev neutron equivalent fluence @xmath2 , where the data has been taken after 1 hour from each end of irradiation . from these plots we have found that the leakage current increases linearly with the fluence . the rates of increase for the both samples are almost the same although the beam flux for sample # 1 is about eight times higher than for sample # 2 . the straight line in the figure shows the linear function fitted to the data of sample # 1 , which gives us the relation between the leakage current and the irradiation dose , @xmath55 = 3.2\times10^{-8}\cdot\phi_{\rm eq}[{\rm n / mm^2}].\ ] ] this information would be useful to compare radiation hardness of other ppd devices with that of mppc . , for sample # 1 ( filled circles ) and sample # 2 ( filled triangles ) . the straight line shows the function fitted to the data for sample # 1 . , width=264 ] -@xmath28 curves of sample # 1 ( top ) and sample # 2 ( bottom ) for different radiation doses . the symbol @xmath56 denotes the breakdown voltage of each sample measured before the irradiation at 27.6 @xmath11c . the symbol @xmath57 indicates the operating voltage given by the manufacturer . , title="fig:",width=264 ] -@xmath28 curves of sample # 1 ( top ) and sample # 2 ( bottom ) for different radiation doses . the symbol @xmath56 denotes the breakdown voltage of each sample measured before the irradiation at 27.6 @xmath11c . the symbol @xmath57 indicates the operating voltage given by the manufacturer . , title="fig:",width=264 ] the @xmath27-@xmath28 curves were measured before and after the irradiation without the led light . the results are shown in fig . [ fig : iv ] . the symbols @xmath56 in the figure denote the breakdown voltages measured before the irradiation ; they are [email protected] v for sample # 1 and [email protected] v for sample # 2 at 27.6 @xmath11c . from these plots , the leakage currents have rapidly increased with reverse voltages after the irradiation in comparison with that before the irradiation . this tendency is more significant for higher doses . next we discuss the effects on photon - counting capability , which is one of the features of mppcs . the pulse - height distributions of the irradiated samples were measured by flushing the blue led . [ fig : adc_dist ] shows the distributions for different irradiated doses . before the irradiation the distributions for both samples show the structure with clear discrete peaks , which includes a pedestal peak , a single photon peak and so on , and those peaks are well separated each other . in contrast , the situation changes after the irradiation . first , the position of the pedestal peak shifts slightly toward lower channels because of the baseline shift coming from high dark counting rates . note that the dark counting rate of mppc increases after the irradiation , which is the main reason for the increase of the leakage current . this is because production of the lattice defects due to radiation damage gives higher probability of thermal carrier generation and delayed pulse coming from trapped carriers in the defects ( afterpulsing ) . actually , the measurement of the counting rates without the led showed that the counting rates drastically increased from 270 khz to 6.8 mhz after the 2.8 gy irradiation ( although we could not measure the counting rates for higher doses due to limitation of the scaler performance , the counting rates would be expected to be more than 10 mhz ) . another thing is that the distributions are contaminated with accidental backgrounds coming from dark noise and afterpulsing as the dose increases . this effect smears the separation of the peaks in the pulse - height distributions as seen in fig . [ fig : adc_dist ] since some of noise pulses are not integrated over the entire charge . gain uniformity among the individual apd pixels may also be deteriorated by radiation damage because if the extent of the damage differs among the pixels , average leakage current through each quenching resistor varies . this results in gain variations among the pixels because of the different voltage drops at the quenching resistors , and thus the peaks could be broadened . for these reasons , the peak structure has completely disappeared for the distributions of more than 21 gy in the case of 55 ns gate width . this means that the capability of the photon - counting by measuring pulse - height spectra was lost due to the radiation damage . the gain variations were evaluated before and after the irradiation . we define the gain of the mppcs as the ratio of the collected charge ( @xmath59 ) and the electron charge ( @xmath60 ) , @xmath61 . the reason is that a single carrier generated by an incident photon is multiplied due to geiger discharge , and then the collected charge in a single pixel is extracted as a output signal . in the data analysis the charge @xmath59 was estimated from the gain of the amplifier , 56.4 , and the charge corresponding to single - photon signals . the charge of single - photon signals was obtained by the fit to the pulse - height distributions with a multi - gaussian function . [ fig : gain - v ] shows the gains as a function of reverse voltages for different radiation doses . note that only the gains for sample # 2 was obtained since we observed no peak structure in the distributions of sample # 1 after the irradiation . the gain before the irradiation shows a linear dependence with the reverse voltage ( @xmath28 ) since the gain of a single pixel ( @xmath62 ) increases with @xmath28 as @xmath63 where @xmath64 denotes the average capacitance of a single pixel , and @xmath56 is the breakdown voltage . the capacitance @xmath64 was estimated to be 0.096 pf from the result of a linear fitting , which is shown as the dotted line in fig . [ fig : gain - v ] . after the irradiation , the data points slightly deviate from a linear relation at higher voltages , where the simple fitting with a multi - gaussian function may be inadequate because of significant accidental backgrounds coming from dark noise and afterpulsing . however , at the operating voltage where those backgrounds would be less affected , gain change is not significant ( within 3% level ) . the result shows that the effect to the gain due to radiation damage is small at least up to 8.0 gy irradiation . note that there is no data point at higher voltages after the irradiation because of the disappearance of the peak structure in the pulse - height distributions . ) fitted to the data before the irradiation . the symbol @xmath57 denotes the operating voltage . , width=283 ] the pulse - height resolution of photo - sensors is one of the most important properties in the case of measurements for the incident - particle s energy . in order to check whether the radiation damage could affect to the pulse - height resolution of the mppcs , we measured the pulse - height distributions of the irradiated samples by illuminating with a led light ( @xmath45 200 photons / mm@xmath1 ) . spectral changes due to the damage can be found by comparing to the distribution taken with a non - irradiated reference sample . this measurement has been performed after 430 days from the irradiation experiment . the irradiated samples , which have been kept in a desiccator at room temperature , have partially recovered from the radiation damage because the leakage current at the operating voltage decreased from 12.0 @xmath9a to 7.1 @xmath9a for sample # 1 , and from 3.3 @xmath9a to 1.6 @xmath9a for sample # 2 , respectively . [ fig : setup_pde ] shows the setup for the measurement . the entire setup was placed in a thermostat oven to ensure temperature stability ( 25 @xmath11c ) and light - tightness . the led light was collimated with a collimator having the hole size of 3 mm@xmath19 and illuminated one of the mppc samples . we aligned the sample with the center of the light spot by using a x - y stage moving with an accuracy of 5 @xmath9 m . the intensity of incident light was controlled with filters placed on the collimator . prior to the measurement , we estimated the absolute number of the photons entering to the active area of the mppc ( @xmath65 ) with a green - extended photo - multiplier tube ( pmt ) , hamamatsu h3178 - 61 . the entrance window of the pmt was masked with black slits having the area of [email protected] mm@xmath1 so as to meet the requirement for the same active area of the mppc . the quantum efficiency of the pmt at the wavelength of 470 nm , which corresponds to the peak wavelength of the led , was measured to be 26.0 % by the manufacturer . two different intensities of light , @xmath66 photons / mm@xmath67 and @xmath68 photons / mm@xmath67 , were illuminated in the measurement . the result is shown in fig . [ fig : lowhigh ] , where pedestal - subtracted adc distributions of the three samples ( reference sample , sample # 2 , and sample # 1 ) are presented for the different light intensities . in the low - intensity case , the peak structure in the distribution of the irradiated samples was smeared due to the radiation damage as discussed in the section [ subsec : pcc ] , although more than a year have elapsed from the irradiation and the recovery effect in the leakage current was observed . in the high - intensity case , the distributions show a gaussian shape having the mean values of about 1760 channels , where the repeatability of the mean - value measurement was evaluated to be about 2% . thus , we found that there was no significant change in the mean value of the pulse height - distribution among the three samples , suggesting that the irradiated samples work well as a photo - sensor even after photon - counting capability was lost . in contrast , the relative width of the distribution slightly widened for sample # 1 whose irradiated dose was 42 gy in total . the measured widths were @xmath69 % for the reference sample , @xmath70 % for sample # 2 , and @xmath71 % for sample # 1 , respectively , where the errors were estimated from gaussian fittings . assuming that the fluctuation caused by radiation damage contributed to the width in quadratic sum , the contribution was estimated to be about 9 % , where the effect of the broadened baseline fluctuation was negligible based on a comparison of the pedestal widths of the reference sample and sample # 1 . in principal , the relative width , which arises because of fluctuations in the number of fired apd - pixels , is given by poisson statistics . thus , the difference of the relative width would be not due to the variability of individual devices , but given due to the radiation damage . some details about the pulse - height resolution will be discussed later . the leakage current of the mppc increased with total irradiated dose as shown in fig . [ fig : i - flux ] . this behavior can be interpreted as an increase of thermal excitations of carriers via intermediate states in the forbidden gap created due to radiation damage . such effect is known to be categorized into bulk damage and surface damage , where the bulk damage is caused by defects in the si bulk and the surface damage is created at the si - sio@xmath15 interface . in the case of proton irradiation , both of them can contribute to the increase of the leakage current . in order to understand the mechanism of proton - induced damage , studies of neutron irradiation would be helpful since the surface damage does not contribute to neutron - induced radiation damage @xcite . photon - counting capability , which is one of the features of mppcs , was gradually deteriorated with the irradiation dose and completely lost after 21 gy irradiation due to baseline fluctuations and noise pileup as a result of increasing dark counting rates . this effect would be problematic for some applications in high - energy physics experiments . for example , when one uses the mppc as a photon - counting device for a ring - imaging cherenkov detector ( rich ) , which detects weak light generated from aerogel radiators , the reconstruction of ring images becomes more difficult due to the increase of fake hits . this point should be carefully considered . on the other hand , for the detectors which is expected to yield more light ( @xmath72 photo - electrons ) , such as scintillators with wavelength - shifting ( wls ) fiber readout , the damage effect might be acceptable at least up to 8.0 gy because no significant change was observed in the gain and the pulse - height distribution . we have found an indication of the deterioration of the pulse - height resolution for the sample irradiated with 42 gy . although we have not understood the mechanism of the deterioration , there are two possible explanations : ( 1 ) change of gain uniformity among the individual pixels and ( 2 ) increase of afterpulsing . the afterpulsing effect would be expected to increase after the irradiation because of radiation damage . hence , increase of afterpulsing could affect to the pulse height distributions . the deterioration of the pulse - height resolution is an issue to be concerned in the case of energy - measurement applications . the effects on mppcs caused by proton irradiation has been discussed from a view point of applications in high radiation environment . in order to investigate the effects of radiation damage , we have performed an irradiation experiment by using a 53.3 mev proton beam . the linear increase of the leakage current has been observed due to radiation damage during the irradiation . we found recovery effects from the radiation damage , however it has not completed even after a year from the irradiation . the result of the gain measurement shows no significant change in the gain at least up to 8.0 gy ( 9.1@xmath0 n / mm@xmath1 in @xmath2 ) . from the measurement of pulse height distribution , we found the photon - counting capability was completely lost due to baseline fluctuations and noise pile - up after 21 gy irradiation ( 2.4@xmath4 n / mm@xmath1 in @xmath2 ) . this effect might be problematic in the case of applications for low light - yield detectors such as rich counter . we found that the pulse - height resolution was slightly deteriorated after 42 gy irradiation ( 4.8@xmath4 n / mm@xmath1 in @xmath2 ) , where the measurement has been performed after 430 days from the irradiation experiment with slightly intense led light ( @xmath73 photons / mm@xmath1 ) . this effect should be considered in the case of energy - measurement applications . we would like to thank the members of the photon sensor group of the kek detector technology project for valuable discussions on radiation damage of the mppcs . we gratefully acknowledge the rcnp cyclotron staff for their kind cooperation in the beam preparation . our thanks go as well to dr . m. hasinoff ( university of british columbia ) who made valuable comments to the paper . the present work was supported in part by the ministry of education , science , sports and culture of japan with the grant - in - aid for scientific research no . 17204020 . 99 d. renker , nucl . instrum . a * 567 * , 48 ( 2006 ) . hamamatsu photonics k.k . , http://www.hamamatsu.com y. itow _ et al . _ , arxiv : hep - ex/0106019 . t. behnke _ et al . _ , ilc reference design report volume 4 - detectors , arxiv:0712.2356 [ physics.ins-det ] . s. hashimoto _ et al . _ , letter of intent for kek super b factory , kek - report-2004 - 4 . j. imazato _ et al . _ , p06 : measurement of t - violating transverse muon polarization in @xmath74 decays , proposal for nuclear and particle physics experiments at j - parc ( 2006 ) . t. yamanaka _ et al . _ , p14 : proposal for @xmath75 experiment at j - parc , proposal for nuclear and particle physics experiments at j - parc ( 2006 ) . s. gomi _ et al . _ , nucl . instrum . a * 581 * , 427 ( 2007 ) . y. musienko , d. renker , s. reucroft , r. scheuermann , a. stoykov and j. swain , nucl . instrum . a * 581 * , 433 ( 2007 ) . t. matsubara , h. tanaka , k. nitta , m. kuze , radiation damage of mppc by @xmath7-ray irradiation with @xmath76co , in proceedings of the international workshop of new photon - detectors ( pd07 ) , june 27 - 29 , 2007 , kobe university , kobe , japan , pos(pd07)032 . g. lindstrom , nucl . instrum . a * 512 * , 30 ( 2003 ) . m. moll , ph.d . thesis , hamburg university , 1999 , desy - thesis-1999 - 040 .

we have investigated the effects caused by proton - induced radiation damage on multi - pixel photon counter ( mppc ) , a pixelized photon detector developed by hamamatsu photonics . the leakage current of irradiated mppc samples linearly increases with total irradiated doses due to radiation damage , which is not completely recovered even after a year from the irradiation . no significant change has been observed in the gains at least up to 8.0 gy ( 9.1@xmath0 n / mm@xmath1 in 1 mev neutron equivalent fluence , @xmath2 ) . the device has completely lost its photon - counting capability due to baseline fluctuations and noise pile - up after 21 gy irradiation ( @xmath3 n / mm@xmath1 in @xmath2 ) , which might be problematic for some applications , such as ring - imaging cherenkov detectors . we have found that the pulse - height resolution has been slightly deteriorated after 42 gy irradiation ( 4.8@xmath4 n / mm@xmath1 in @xmath2 ) , where the measured sample has been illuminated with a few hundred photons . this effect should be considered in the case of energy - measurement applications . , , , , , , , , , , radiation damage , mppc , sipm , ppd , photon detector 29.40.wk

gastric cancer is the fourth most common malignancy worldwide , and most common malignancy in korea . although survival time has been lengthened , the life expectancy of advanced disease still remains within one year . for patients with advanced gastric carcinoma or recurrent cancer , the response rate ( rr ) for first - line chemotherapy ranges from 33 - 55% , and the survival time following chemotherapy is superior to that of patients given best supportive care . despite poorer survival benefit and tolerance of second - line chemotherapy , about 20% of patients with failure of first - line chemotherapy receive second - line chemotherapy . asian studies have reported a rr of second - line chemotherapy as 5 - 25% and progression - free survival ( pfs ) of 5.2 - 8.8 months . many clinicians consider second - line chemotherapy after failure of first - line chemotherapy for patients with advanced gastric carcinoma . there is a controversy about the benefit of sequential salvage therapy further to second - line . however , with prolonged survival time of patients and tolerable toxicity of drugs , there has been renewed interest in chemotherapy after failure of second - line treatments . it has been our empiric observation that some patients maintain good performance after failure of second - line chemotherapy , and live longer with salvage chemotherapy than other patients with supportive care . the aim of the present study was to clarify the relationship between the sequence of second- and third - line chemotherapy regimen including taxane and irinotecan with survival of patients , and to identify clinical characteristics of patients with better response to salvage chemotherapy than others . we retrospectively evaluated the medical records of advanced or recurred gastric carcinoma patients who were diagnosed and treated at gangnam severance hospital between november 2004 and july 2010 . patients who met the following criteria were eligible : histologically proven advanced gastric adenocarcinoma with metastatic or recurrent disease ; received third - line chemotherapy at gangnam severance hospital using folinic acid , 5-fluorouracil ( 5-fu ) and oxaliplatin ( folfox ) or 5-fu+cisplatin ( fp ) , folinic acid , 5-fu and irinotecan ( folfiri ) , paclitaxel or docetaxel with 5-fu , with or without epirubicin ; measurable lesion according to the response evaluation criteria in solid tumors ( recist ) or a non - measurable lesion , assessed using either computed tomography ( ct ) or magnetic resonance imaging ; 18 - 75 years of age ; eastern cooperative oncology group ( ecog ) performance status2 ; life expectancy of at least 3 months ; and adequate hematologic function , evident as absolute neutrophil count1500/l , platelet count100,000/l , hepatic function ( total bilirubin2 times the upper normal limit [ unl ] , serum transaminase level2 times the unl ) and renal function ( serum creatine1.5 times the unl ) . exclusion criteria were the presence of other severe medical illness , central nervous system metastasis , another active malignancy , or history of anaphylaxis to drugs . clinical information included gender , age at diagnosis , ecog performance status , pathologic differentiation , lauren classification , coexisting peritoneal or hepatic metastases , date of chemotherapy , and number of cycles . in addition , laboratory data including hemoglobin , serum albumin , carcinoembryonic antigen ( cea ) , and cancer antigen ( ca ) 19 - 9 were also reviewed . sequential chemotherapy was defined as chemotherapy using more than two different chemotherapeutic regimens performed consecutively . patients were assigned to either arm a or arm b , according to the sequence of three chemotherapeutic regimens . arm a comprised folfox or fp for first - line chemotherapy ; folfiri for second - line chemotherapy ; and docetaxel or paclitaxel , leucovorin , and 5-fu ( with or without epirubicin ) for third - line chemotherapy . in arm b , patients were treated with folfox or fp for first - line chemotherapy ; docetaxel or paclitaxel , leucovorin , and fu with or without epirubicin for second - line chemotherapy ; and folfiri for third - line chemotherapy . patients received oxaliplatin ( 100 mg / m in 500 ml normal saline ) or 5% dextrose water over 2 hours followed by leucovorin ( 100 mg / m ) over 2 hours on day 1 and continuous infusion of 5-fu 1,000 mg / m / day for 2 days . cisplatin ( 70 mg / m in 500 ml normal saline ) or 5% dextrose water was intravenously administered over 2 hours on day 1 followed by continuous infusion of 5-fu ( 1,000 mg / m / day ) for 2 days . irinotecan ( 150 mg / m in 500 ml normal saline ) was intravenously administered over 2 hours on followed by leucovorin ( 100 mg / m over 2 hours ) on day 1 and 5-fu ( 1,000 docetaxel ( 75 mg / m in 500 ml normal saline ) or paclitaxel ( 175 mg / m in 500 ml normal saline ) was intravenously administered over 2 hours followed by leucovorin ( 100 mg / m over 2 hours ) on day 1 and 5-fu ( 1,000 for some patients , epirubicin ( 50 mg / m in 100 ml normal saline ) was intravenously administered over 30 minutes on day 2 . response was assessed after two cycles of chemotherapy and when disease progression was clinically suspected . a measurable lesion was defined as a lesion with the longest diameter 10 mm in any dimension assessed by spiral ct imaging . tumor response was evaluated according to the recist guidelines as follows : complete response ( cr ) if all target lesions disappeared , partial response ( pr ) if the sum of diameters of the target lesions decreased by at least 30% , progressive disease ( pd ) if the sum of the longest diameters of the target lesions increased by at least 20% and one or more new lesions appeared , and stable disease ( sd ) for responses that were neither pr nor pd . the rr was defined as proportion of the patients with responses of cr or pr out of all patients . overall survival ( os ) was defined as the interval from the first date of chemotherapy to death or the last follow - up date . time to progression ( ttp ) was defined as the time from the first date of chemotherapy to the time of progression of the disease or the last follow - up date . the kaplan - meier method was used for survival analysis , and survival curves were compared assessed using the log - rank test . following variables were included in univariate analysis : age at diagnosis , gender , performance status by ecog criteria , pathologic differentiation , coexisting peritoneal or hepatic metastases , type of chemotherapeutic regimen , hemoglobin , serum albumin , cea , ca19 - 9 , and ttp of first- or second - line chemotherapy . for variables with a probability p - value0.3 in univariate analysis , multivariate analysis was also performed using the cox 's proportional hazard regression model ( two - sided ) . we retrospectively evaluated the medical records of advanced or recurred gastric carcinoma patients who were diagnosed and treated at gangnam severance hospital between november 2004 and july 2010 . patients who met the following criteria were eligible : histologically proven advanced gastric adenocarcinoma with metastatic or recurrent disease ; received third - line chemotherapy at gangnam severance hospital using folinic acid , 5-fluorouracil ( 5-fu ) and oxaliplatin ( folfox ) or 5-fu+cisplatin ( fp ) , folinic acid , 5-fu and irinotecan ( folfiri ) , paclitaxel or docetaxel with 5-fu , with or without epirubicin ; measurable lesion according to the response evaluation criteria in solid tumors ( recist ) or a non - measurable lesion , assessed using either computed tomography ( ct ) or magnetic resonance imaging ; 18 - 75 years of age ; eastern cooperative oncology group ( ecog ) performance status2 ; life expectancy of at least 3 months ; and adequate hematologic function , evident as absolute neutrophil count1500/l , platelet count100,000/l , hepatic function ( total bilirubin2 times the upper normal limit [ unl ] , serum transaminase level2 times the unl ) and renal function ( serum creatine1.5 times the unl ) . exclusion criteria were the presence of other severe medical illness , central nervous system metastasis , another active malignancy , or history of anaphylaxis to drugs . clinical information included gender , age at diagnosis , ecog performance status , pathologic differentiation , lauren classification , coexisting peritoneal or hepatic metastases , date of chemotherapy , and number of cycles . in addition , laboratory data including hemoglobin , serum albumin , carcinoembryonic antigen ( cea ) , and cancer antigen ( ca ) 19 - 9 were also reviewed . sequential chemotherapy was defined as chemotherapy using more than two different chemotherapeutic regimens performed consecutively . patients were assigned to either arm a or arm b , according to the sequence of three chemotherapeutic regimens . arm a comprised folfox or fp for first - line chemotherapy ; folfiri for second - line chemotherapy ; and docetaxel or paclitaxel , leucovorin , and 5-fu ( with or without epirubicin ) for third - line chemotherapy . in arm b , patients were treated with folfox or fp for first - line chemotherapy ; docetaxel or paclitaxel , leucovorin , and fu with or without epirubicin for second - line chemotherapy ; and folfiri for third - line chemotherapy . patients received oxaliplatin ( 100 mg / m in 500 ml normal saline ) or 5% dextrose water over 2 hours followed by leucovorin ( 100 mg / m ) over 2 hours on day 1 and continuous infusion of 5-fu 1,000 mg / m / day for 2 days . cisplatin ( 70 mg / m in 500 ml normal saline ) or 5% dextrose water was intravenously administered over 2 hours on day 1 followed by continuous infusion of 5-fu ( 1,000 irinotecan ( 150 mg / m in 500 ml normal saline ) was intravenously administered over 2 hours on followed by leucovorin ( 100 mg / m over 2 hours ) on day 1 and 5-fu ( 1,000 docetaxel ( 75 mg / m in 500 ml normal saline ) or paclitaxel ( 175 mg / m in 500 ml normal saline ) was intravenously administered over 2 hours followed by leucovorin ( 100 mg / m over 2 hours ) on day 1 and 5-fu ( 1,000 for some patients , epirubicin ( 50 mg / m in 100 ml normal saline ) was intravenously administered over 30 minutes on day 2 . response was assessed after two cycles of chemotherapy and when disease progression was clinically suspected . a measurable lesion was defined as a lesion with the longest diameter 10 mm in any dimension assessed by spiral ct imaging . tumor response was evaluated according to the recist guidelines as follows : complete response ( cr ) if all target lesions disappeared , partial response ( pr ) if the sum of diameters of the target lesions decreased by at least 30% , progressive disease ( pd ) if the sum of the longest diameters of the target lesions increased by at least 20% and one or more new lesions appeared , and stable disease ( sd ) for responses that were neither pr nor pd . the rr was defined as proportion of the patients with responses of cr or pr out of all patients . patients received oxaliplatin ( 100 mg / m in 500 ml normal saline ) or 5% dextrose water over 2 hours followed by leucovorin ( 100 mg / m ) over 2 hours on day 1 and continuous infusion of 5-fu 1,000 mg / m / day for 2 days . cisplatin ( 70 mg / m in 500 ml normal saline ) or 5% dextrose water was intravenously administered over 2 hours on day 1 followed by continuous infusion of 5-fu ( 1,000 mg / m / day ) for 2 days . irinotecan ( 150 mg / m in 500 ml normal saline ) was intravenously administered over 2 hours on followed by leucovorin ( 100 mg / m over 2 hours ) on day 1 and 5-fu ( 1,000 docetaxel ( 75 mg / m in 500 ml normal saline ) or paclitaxel ( 175 mg / m in 500 ml normal saline ) was intravenously administered over 2 hours followed by leucovorin ( 100 mg / m over 2 hours ) on day 1 and 5-fu ( 1,000 for some patients , epirubicin ( 50 mg / m in 100 ml normal saline ) was intravenously administered over 30 minutes on day 2 . response was assessed after two cycles of chemotherapy and when disease progression was clinically suspected . a measurable lesion was defined as a lesion with the longest diameter 10 mm in any dimension assessed by spiral ct imaging . tumor response was evaluated according to the recist guidelines as follows : complete response ( cr ) if all target lesions disappeared , partial response ( pr ) if the sum of diameters of the target lesions decreased by at least 30% , progressive disease ( pd ) if the sum of the longest diameters of the target lesions increased by at least 20% and one or more new lesions appeared , and stable disease ( sd ) for responses that were neither pr nor pd . the rr was defined as proportion of the patients with responses of cr or pr out of all patients . overall survival ( os ) was defined as the interval from the first date of chemotherapy to death or the last follow - up date . time to progression ( ttp ) was defined as the time from the first date of chemotherapy to the time of progression of the disease or the last follow - up date . the kaplan - meier method was used for survival analysis , and survival curves were compared assessed using the log - rank test . following variables were included in univariate analysis : age at diagnosis , gender , performance status by ecog criteria , pathologic differentiation , coexisting peritoneal or hepatic metastases , type of chemotherapeutic regimen , hemoglobin , serum albumin , cea , ca19 - 9 , and ttp of first- or second - line chemotherapy . for variables with a probability p - value0.3 in univariate analysis , multivariate analysis was also performed using the cox 's proportional hazard regression model ( two - sided ) . between november 2004 and july 2010 , 50 patients with gastric carcinoma were treated with a sequential chemotherapy protocol , based only on folfox or fp , folfiri , and paclitaxel or docetaxel , at gangnam severance hospital . the median age was 52.5 years ( range , 29 to 70 years ) , and 34 patients ( 68% ) were male . forty subjects ( 80% ) had good performance status ( ecog 0 - 1 ) . seven patients had diffuse type , 13 patients had interstitial type , and the other two patients had mixed type adenocarcinoma . no significant difference except for peritoneal carcinomatosis was observed . fifty patients received median fourth - line chemotherapy ( range , 3 to 10 ) , and a median of 18 cycles ( range , 4 to 60 cycles ) were administered . median os of all patients was 16.0 months ( 95% confidence interval [ ci ] , 13.6 to 18.3 months ) ( fig . 1 ) , and median ttp was 5.0 months ( 95% ci , 3.9 to 6.1 months ) in first - line chemotherapy , 2.4 months ( 95% ci , 1.6 to 3.2 months ) in second - line chemotherapy , and 2.5 months ( 95% ci , 1.8 to 3.3 months ) in third - line chemotherapy . the median os time of arm a and arm b was 17.1 months ( 95% ci , 10.7 to 23.6 months ) , and 15.4 months ( range , 13.8 to 17.1 months ) , respectively . 1 ) . ttp of arm a and arm b with first - line chemotherapy was 5.5 months ( 95% ci , 1.2 to 9.8 months ) and 4.8 months ( 95% ci , 3.8 to 5.8 months ) , respectively ( p=0.064 ) . for the second - line chemotherapy , ttp of arm a and arm b was 2.7 months and 2.2 months , respectively ( p=0.850 ) . each ttp of the two groups were 2.2 months in arm a and 2.7 months in arm b ( p=0.297 ) . in addition , we analyzed clinicopathologic characteristics of the patients . patients with poorly - differentiated adenocarcinoma or signet ring cell feature showed poorer prognosis than others . furthermore , elevated cea level and shorter ttp of first - line chemotherapy were significantly related with shorter survival times ( table 2 ) . the rr was 50% for first - line chemotherapy , 8% for second - line chemotherapy , and 8.5% for third - line chemotherapy . in second - line chemotherapy , rr was 11.1% in arm a and 6.3% in arm b. in third - line chemotherapy , rr was 6.3% in arm a and 9.7% in arm b. the disease control rate ( dcr ) which was determined by the disease status ( cr , pr , or sd ) controlled by treatment , of first - line chemotherapy was 88.9% in arm a and 78.1% in arm b ( p=0.342 ) . in second - line chemotherapy , dcr of arm a was 38.9% , and that of arm b was 53.1% ( p=0.333 ) . in third - line chemotherapy , dcr was 25% in arm a and 41.9% in arm b ( p=0.252 ) . twenty - one patients did not show any response ( pr or cr ) to any of the three sequential chemotherapies . the median os was 20.0 months ( 95% ci , 2.4 to 37.5 months ) in the good - responders and 13.9 months ( 95% ci , 12.0 to 15.8 months ) in the poor - responders . between november 2004 and july 2010 , 50 patients with gastric carcinoma were treated with a sequential chemotherapy protocol , based only on folfox or fp , folfiri , and paclitaxel or docetaxel , at gangnam severance hospital . the median age was 52.5 years ( range , 29 to 70 years ) , and 34 patients ( 68% ) were male . forty subjects ( 80% ) had good performance status ( ecog 0 - 1 ) . seven patients had diffuse type , 13 patients had interstitial type , and the other two patients had mixed type adenocarcinoma . no significant difference except for peritoneal carcinomatosis was observed . fifty patients received median fourth - line chemotherapy ( range , 3 to 10 ) , and a median of 18 cycles ( range , 4 to 60 cycles ) were administered . median os of all patients was 16.0 months ( 95% confidence interval [ ci ] , 13.6 to 18.3 months ) ( fig . 1 ) , and median ttp was 5.0 months ( 95% ci , 3.9 to 6.1 months ) in first - line chemotherapy , 2.4 months ( 95% ci , 1.6 to 3.2 months ) in second - line chemotherapy , and 2.5 months ( 95% ci , 1.8 to 3.3 months ) in third - line chemotherapy . the median os time of arm a and arm b was 17.1 months ( 95% ci , 10.7 to 23.6 months ) , and 15.4 months ( range , 13.8 to 17.1 months ) , respectively . 1 ) . ttp of arm a and arm b with first - line chemotherapy was 5.5 months ( 95% ci , 1.2 to 9.8 months ) and 4.8 months ( 95% ci , 3.8 to 5.8 months ) , respectively ( p=0.064 ) . for the second - line chemotherapy , ttp of arm a and arm b was 2.7 months and 2.2 months , respectively ( p=0.850 ) . each ttp of the two groups were 2.2 months in arm a and 2.7 months in arm b ( p=0.297 ) . patients with poorly - differentiated adenocarcinoma or signet ring cell feature showed poorer prognosis than others . furthermore , elevated cea level and shorter ttp of first - line chemotherapy were significantly related with shorter survival times ( table 2 ) . the rr was 50% for first - line chemotherapy , 8% for second - line chemotherapy , and 8.5% for third - line chemotherapy . in second - line chemotherapy , rr was 11.1% in arm a and 6.3% in arm b. in third - line chemotherapy , rr was 6.3% in arm a and 9.7% in arm b. the disease control rate ( dcr ) which was determined by the disease status ( cr , pr , or sd ) controlled by treatment , of first - line chemotherapy was 88.9% in arm a and 78.1% in arm b ( p=0.342 ) . in second - line chemotherapy , dcr of arm in third - line chemotherapy , dcr was 25% in arm a and 41.9% in arm b ( p=0.252 ) . twenty - one patients did not show any response ( pr or cr ) to any of the three sequential chemotherapies . the median os was 20.0 months ( 95% ci , 2.4 to 37.5 months ) in the good - responders and 13.9 months ( 95% ci , 12.0 to 15.8 months ) in the poor - responders . it has generally been accepted that palliative chemotherapy can significantly prolong survival of patients with advanced gastric carcinoma , longer than best supportive care . platinum - based chemotherapy is widely - used as first - line chemotherapy for advanced gastric cancer . given the reported tolerance and survival benefits of second - line chemotherapy , studies have sought to identify the benefit and adequate regimen of second - line chemotherapy . the current study evaluated two groups of gastric cancer patients who received third - line chemotherapy . previous studies reported the median pfs of 2.5 - 3.3 months and the median os of 5.3 - 8.7 months in gastric cancer patients who received second - line chemotherapy [ 6,8 - 10 ] . in this study , the median pfs was 2.4 months ( 95% ci , 1.6 to 3.2 months ) for patients treated with second - line chemotherapy , similar to the previous report . the median os was 16.0 months ( 95% ci , 13.6 to 18.3 months ) , and 32.0% of patients survived after 2 years . these times were slightly longer than that of historical control . we suggest that this is due to sequential treatment of the patients . this study included a restricted population with a performance status that permitted the use of third - line chemotherapy after failure of second - line chemotherapy . therefore , this result was subject to limitation in comparison with other survival data of patients without third - line chemotherapy . nevertheless , based on 2.5 months of median ttp in third - line chemotherapy , the authors suggest that third - line chemotherapy would provide a survival benefit for patients with favorable performance status . in many phase ii clinical trials of second - line chemotherapy for advanced gastric cancer , rr was about 20.8% , and dcr was about 51% . in the present study , rr for second - line chemotherapy was 8% and dcr was 48% . there is still little information to support the provision of a second - line chemotherapeutic regimen after failure of platinum - based first - line chemotherapy . reported that sequential chemotherapy appears to be both a feasible and effective treatment for advanced gastric cancer . their sequential protocol was s-1 based chemotherapy for first - line chemotherapy , a low dose irinotecan / cisplatin for second - line chemotherapy , and paclitaxel for third - line chemotherapy . thirty - two gastric cancer patients showed relatively long median survival ( 17.4 months ; 95% ci , 323 to 723 days ) . this result shows that a consecutive use of chemotherapy has a substantial impact on os of gastric cancer patients . these facts also demonstrate that second- and third - line chemotherapy is necessary to treat advanced gastric cancer . many clinicians consider the folfiri regimen and paclitaxel or docetaxel with 5-fu regimen as second - line chemotherapy after failure of platinum - based first line chemotherapy . numerous physicians suggested that folfiri is tolerable and has a modest effect as a second - line chemotherapy for gastric carcinoma . in an asian study , the median pfs was 3.2 months , and the median os was 9.1 months . in another study , rr was 18.2% , median os was 5.1 months , and median ttp was 2.3 months . on the other hand , the tolerance and effectiveness of taxane - based chemotherapy apparent in several studies ( median ttp , 2.6 - 3.9 months ; median os , 7.2 to 10.1 months ) warrants its use as second - line chemotherapy in advanced gastric carcinoma . kim et al . reported that overall rr and dcr for patients with docetaxel / cisplatin followed by folfiri and patients with folfiri followed by a docetaxel / cisplatin regimen showed no significant difference . however , to the best of our knowledge , survival benefits according to sequence of regimens of second - line and third - line chemotherapy after failure of first line chemotherapy have not been reported . in this study , we analyzed 50 patients treated with either folfox or fp chemotherapy followed by folfiri , and paclitaxel or docetaxel , or folfox or fp chemotherapy followed by paclitaxel or docetaxel , and folfiri regimen . however , we found some patients responded better to chemotherapy , and their os was longer than the others . previous investigators suggested that low hemoglobin level , low serum albumin level , high cea level , poor performance status [ 8 - 10,16,17 ] , shorter ttp of first - line chemotherapy , shorter ttp of second - line chemotherapy , and poor differentiation of tumor are poor prognostic factors for patients with gastric carcinoma under sequential chemotherapy . we analyzed the previously reported factors and found some differences in survival according to histologic differentiation , elevated cea level , and ttp of first line chemotherapy in this study . there has been a controversy regarding the influence of the histological feature of signet ring cell on the prognosis of gastric carcinoma . some researchers reported poorer prognosis of advanced gastric carcinoma with signet ring cell histology , while better prognosis of early gastric carcinoma with signet ring cell histology has been reported . in this study , gastric adenocarcinoma with poorly differentiated or signet ring cell features had poorer response to sequential chemotherapy , and had shorter median os than well or moderately differentiated ones . concerning cea level , some investigators reported the relationship of serum cea level with tumor invasion , lymph node metastasis , and higher recurrence rate . herein , we suggest that differences in gene and protein expressions are other prognostic values that should be taken into account . in a recent study , we suppose that there are some genetic differences in diffuse gastric adenocarcinoma and that the different genetic defect influences a poorer response to sequential chemotherapy . furthermore , cea is a widely used tumor marker , and the cea gene has been widely - used as a tumor - specific promoter and target of treatment over the last decade . we propose that the difference in response could also be attributed to the differences in gene expression profiles between the two groups . in recent years , it has become clear that a pharmacogenic approach is a potential tool for optimizing treatment for several human tumors . the ability of genetic polymorphisms to influence pharmacogenetics of 5-fu , platinum derivatives , anthracyclines , irinotecan , and docetaxel in gastric cancer has been reported . the use of multiple gene analyses in the development of individualized gastric cancer chemotherapies could be helpful in selecting patients who are more likely to benefit better to a particular therapy . the possible prediction of cancer outcome from gene expression classifiers , sets of genes , or signatures associated with prognosis together with classification rules has been suggested . limitations of this study include the retrospective study design and small patient pool . nevertheless , the results of this study provides evidence that third - line chemotherapy , including folfox or fp , folfiri , paclitaxel or docetaxel regimen , helps to improve os of patients , regardless of the sequence of use of taxane and irinotecan . in addition , os seems to be poorly affected by poorly differentiated or signet ring cell feature of adenocarcinoma , elevated cea level , and shorter ttp of first - line chemotherapy . different chemotherapy - responses to locally advanced or metastatic gastric carcinoma treated with second and third - line chemotherapy using irinotecan or taxane could be attributed not to sequence of chemotherapeutic regimen , but to patients ' different clinical features underlying different gene expression profiles . future studies will be required to investigate the impact of genetic difference on response to sequential chemotherapy .

purposethe aims of this study are to find out whether the sequence of chemotherapeutic regimens including second- and third - line taxane and irinotecan influences the survival of patients with unresectable gastric carcinoma and to identify clinical characteristics of patients with improved response.materials and methodsfifty gastric carcinoma patients who were treated by third - line sequential chemotherapy between november 2004 and july 2010 were enrolled in this study . their overall survival ( os ) and time to progression ( ttp ) were set up as primary and secondary end points . for the sequence of chemotherapy regimen , two arms were used . arm a was defined as 5-fluorouracil ( 5-fu)+cisplatin ( fp ) or folinic acid , 5-fu and oxaliplati ( folfox ) , followed by folinic acid , 5-fu and irinotecan ( folfiri ) , and paclitaxel or docetaxel plus 5-fu , with or without epirubicin . arm b was defined as fp or folfox , followed by paclitaxel or docetaxel plus 5-fu , and folfiri.resultsthe median os of all patients was 16.0 months ( 95% confidence interval , 13.6 to 18.3 months ) , which is longer than historical control of patients who did not receive third - line chemotherapy . the sequence of second and third - line regimen , including irinotecan and taxane , did not present significant difference in os or ttp after failure of 5-fu with platinum chemotherapy . in survival analysis of patients ' clinicopathologic characteristics , poor prognosis was shown in patients with poorly differentiated histologic features , elevated serum carcinoembryonic level , and shorter ttp of first line chemotherapy.conclusionit is possible for patients to respond differently to chemotherapy due to differences in clinical features and underlying gene expression profiles . development of individualized chemotherapy regimens based on gene expression profiles is warranted .

The sacrifice of a Chinese television presenter, who died of cancer after refusing chemotherapy treatment while pregnant to stop her unborn child being harmed – has touched the hearts of thousands of people on the mainland. Qiu Yuanyuan, 26, from Zhengzhou, in the central province of Henan, died on Wednesday – exactly 100 days after giving birth to her son, Niannian. After getting married, becoming a mother was her biggest wish Qiu Yuanyuan’s husband, Zhang Qixuan The story of her selfless act has been one of the hottest topics on China’s microblogging site Weibo since yesterday, and reached more than 10 million views by this morning. Thousands of Weibo users, moved by her great courage and love for her baby son, posted comments commemorating Qiu and wishing her son a long and healthy life on Qui’s Weibo page. “After getting married, becoming a mother was her biggest wish,” Qiu’s husband, Zhang Qixuan, told the Zhengzhou Evening News. “She chose to save our child; she understood that not everything in life can be perfect. And she said she had never regretted her decision.” She chose to save our child; she understood that not everything in life can be perfect. And she said she had never regretted her decision Qiu Yuanyuan’s husband, Zhang Qixuan Qiu, who had hosted of a chess games show on Zhengzhou Television Station, learned she was pregnant in March. However, her happiness was cut short after the results of a physical examination revealed that Qiu was suffering from a late-stage malignant tumour, the newspaper reported. In order to prevent the baby being harmed by her chemotherapy, Qiu agreed to halt her treatment, which allowed the cancer to spread. When Qiu’s condition deteriorated in September, she was admitted to hospital where her son, Niannian – then only seven months old – was delivered by Caesarean section. The boy weighed a little more than 1.5kg at the time of the birth, the report said. Qiu then underwent an operation for the removal of the malignant tumour, but it came too late to save her. Despite undergoing more than 20 days of chemotherapy, her doctors said the chances of her being cured were very low. They advised Qiu to halt her remaining therapy and return home to her baby son. She died at her home on Wednesday evening, after her family held a feast to celebrate the baby’s 100th day since his birth – a traditional custom widely practiced by Chinese families. The report said Qiu’s husband, who worked as a journalist at the same TV station as Qiu, was way from home when she died, and was unable to be with her at the time. “Yuanyuan has passed away; the only thing I can do now is to take care our child and her family,” her husband was quoted as saying. “I hope everyone can silently bless her and our child, and smile at life – just as Yuanyuan did.” ||||| The fate of a Chinese television presenter who died of cancer after refusing chemotherapy to save her unborn son sparked intense online debate Friday. Qiu Yuanyuan died on Wednesday aged 26, 100 days after giving birth to her child -- a special occasion in Chinese culture. More than 10 million netizens viewed her story on China's Twitter-like Sina Weibo on Friday, but many of those commenting questioned why she had sacrificed her life. "I don't think it's good to give up on living, even if the mother's love is great," posted one netizen. "It's not a beautiful thing if a child is born with no care and love from its natural mother." Qiu, from the central province of Henan, was told she was pregnant in March, the website of the People's Daily newspaper said. View gallery Family members and friends mourn during the funeral ceremony of Qiu Yuanyuan, a Chinese television p … But her "hope turned to despair" soon after when she was diagnosed with a late-stage cancer of the womb, it went on. Qiu decided to halt her treatment to prevent her baby being harmed, and the cancer soon spread. As her condition worsened, she was admitted to hospital in September when she gave birth to the boy, named Niannian. She eventually died as the family were celebrating his 100th day. "Leaving a little life alone in the world, such a heartless mother," another netizen said. Others, however, were more sympathetic to her plight. "Even chemotherapy cannot cure cancer, can it? So she chose this way, wise and helpless," said one poster. Another added: "Mother's love is so great."

– An up-and-coming TV host in Zhengzhou, China, always gave as much time as she could to her job, often working 14-hour days without complaint, a co-worker says. But when Qiu Yuanyuan became pregnant in March, her focus switched over to her unborn child—so much so that when she found out she had late-stage womb cancer in July, she opted not to go forward with chemo to protect her baby, Shanghaiist reports. In September she gave birth to 3.3-pound Niannian two months early via C-section, after which doctors tried to remove her tumor and begin chemo, but it was too late: Qiu died this month at home on Niannian's 100th day, a traditional Chinese celebration, the South China Morning Post reports. Qiu's choice has launched a back-and-forth online, with some lauding the young mother for a courageous, selfless act, and others insisting she should've tried harder to stay alive. One commenter in an online forum writes, "She's a goddess and great mother. R.I.P.," as per Shanghaiist, while AFP mentions a Sina Weibo lament that states, "It's not a beautiful thing if a child is born with no care and love from its natural mother"; another commenter piles on: "Leaving a little life alone in the world, such a heartless mother." Qiu's husband, a reporter at the same station as his wife, tells the Zhengzhou Evening News that her "biggest wish" had been to be a mom. "She chose to save our child; she understood that not everything in life can be perfect," he says, per the Morning Post. "And she said she had never regretted her decision." (A Colorado woman's family says her decision to have a C-section was the ultimate motherly sacrifice.)

in wireless communication networks , multiple users often share a common channel and contend for access . to resolve the contention problem , many different medium access control ( mac ) protocols have been devised and used . recently , the selfish behavior of users in mac protocols has been studied using game theory . there have been attempts to understand the existing mac protocols as the local utility maximizing behavior of selfish users by reverse - engineering the current protocols ( e.g. , @xcite ) . it has also been investigated whether existing protocols are vulnerable to the existence of selfish users who pursue their self - interest in a non - cooperative manner . non - cooperative behavior often leads to inefficient outcomes . for example , in the 802.11 distributed mac protocol , dcf , and its enhanced version , edcf , competition among selfish users can lead to an inefficient use of the shared channel in nash equilibria @xcite . similarly , a prisoner s dilemma phenomenon arises in a non - cooperative game for a generalized version of slotted - aloha protocols @xcite . in general , if a game has nash equilibria yielding low payoffs for the players , it will be desirable for them to transform the game to extend the set of equilibria to include better outcomes @xcite . the same idea can be applied to the game played by selfish users who compete for access to a common medium . if competition among selfish users brings about a network collapse , then it is beneficial for them to design a device which provides incentives to behave cooperatively . game theory @xcite discusses three types of transformation : 1 ) games with contracts , 2 ) games with communication , and 3 ) repeated games . a game is said to be with contracts if the players of the game can communicate and bargain with each other , and enforce the agreement with a binding contract . the main obstacle to apply this approach to wireless networking is the distributed nature of wireless networks . to reach an agreement , users should know the network system and be able to communicate with each other . they should also be able to enforce the agreed plan . a game with communication is the one in which players can communicate with each other through a mediator but they can not write a binding contract . in this case , a correlated equilibrium is predicted to be played . @xcite studies correlated equilibria using a coordination mechanism in a slotted aloha - type scenario . unlike the first approach , this does not require that the actions of players be enforceable . however , to apply this approach to the medium access problem , signals need to be conveyed from a mediator to all users , and users need to know the correct meanings of the signals . a repeated game is a dynamic game in which the same game is played repeatedly by the same players over finite or infinite periods . repeated interactions among the same players enable them to sustain cooperation by punishing deviations in subsequent periods . a main challenge of applying the idea of repeated games to wireless networks is that the users should keep track of their past observations and be able to detect deviations and to coordinate their actions in order to punish deviating users . besides the three approaches above , another approach widely applied to communication networks is pricing @xcite . a central entity charges prices to users in order to control their utilization of the network . nash equilibria with pricing schemes in an aloha network are analyzed in @xcite . implementing a pricing scheme requires the central entity to have relevant system information as well as users benefits and costs , which are often their private information . eliciting private information often results in an efficiency loss in the presence of the strategic behavior of users as shown in @xcite . even in the case where the entity has all the relevant information , prices need to be computed and communicated to the users . in this paper , we propose yet another approach using a stackelberg game . we introduce a network manager as an additional user and make him access the medium according to a certain rule . unlike the stackelberg game of @xcite in which the manager ( the leader ) chooses a certain strategy before users ( followers ) make their decisions , in the proposed stackelberg game he sets an intervention rule first and then implements his intervention after users choose their strategies . alternatively , the proposed stackelberg game can be considered as a generalized stackelberg game in which there are multiple leaders ( users ) and a single follower ( the manager ) and the leaders know the response of the follower to their decisions correctly . with appropriate choices of intervention rules , the manager can shape the incentives of users in such a way that their selfish behavior results in cooperative outcomes . in the context of cognitive radio networks , @xcite proposes a related stackelberg game in which the owner of a licensed frequency band ( the leader ) can charge a virtual price for using the frequency band to cognitive radios ( followers ) . the virtual price signals the extent to which cognitive radios can exploit the licensed frequency band . however , since prices are virtual , selfish users may ignore prices when they make decisions if they can gain by doing so . on the contrary , in the stackelberg game of this paper , the intervention of the manager is not virtual but it results in the reduction of throughput , which selfish users care about for sure . hence , the intervention method provides better grounds for the network manager to deal with the selfish behavior of users . @xcite and @xcite use game theoretic models to study random access . their approach is to capture the information and implementation constraints using the game theoretic framework and to specify utility functions so that a desired operating point is achieved at a nash equilibrium . if conditions under which a certain type of dynamic adjustment play converges to the nash equilibrium are met , such a strategy update mechanism can be used to derive a distributed algorithm that converges to the desired operating point . however , this control - theoretic approach to game theory assumes that users are obedient . in this paper , our main concern is about the selfish behavior of users who have innate objectives . because we start from natural utility functions and affect them by devising an intervention scheme , we are in a better position to deal with selfish users . furthermore , the idea of intervention can potentially lead to a distributed algorithm to achieve a desired operating point . by formulating the medium access problem as a non - cooperative game , we show the following main results : 1 . because the nash equilibria of the non - cooperative game are inefficient and/or unfair , we transform the original game into a stackelberg game , in which any feasible outcome with independent transmission probabilities can be achieved as a stackelberg equilibrium . a particular form of a stackelberg intervention strategy , called total relative deviation ( trd)-based intervention , is constructed and used to achieve any feasible outcome with independent transmission probabilities . the additional amount of information flows required for the transformation is relatively moderate , and it can be further reduced without large efficiency losses . the rest of this paper is organized as follows . section 2 introduces the model and formulates it as a non - cooperative game called the contention game . nash equilibria of the contention game are characterized , and it is shown that they typically yield suboptimal performance . in section 3 , we transform the contention game into another related game called the stackelberg contention game by introducing an intervening manager . we show that the manager can implement any transmission probability profile as a stackelberg equilibrium using a class of intervention functions . section 4 discusses natural candidates for the target transmission probability profile selected by the manager . in section 5 , we discuss the flows of information required for our results and examine the implications of some relaxations of the requirements on performance . section 6 provides numerical results , and section 7 concludes the paper . we consider a simple contention model in which multiple users share a communication channel as in @xcite . a user represents a transmitter - receiver pair . time is divided into slots of the same duration . every user has a packet to transmit and can send the packet or wait . if there is only one transmission , the packet is successfully transmitted within the time slot . if more than one user transmits a packet simultaneously in a slot , a collision occurs and no packet is transmitted . we summarize the assumptions of our contention model . 1 . a fixed set of users interacts over a given period of time ( or a session ) . time is divided into multiple slots , and slots are synchronized . a user always has a packet to transmit in every slot . the transmission of a packet is completed within a slot . a user transmits its packet with the same probability in every slot . there is no adjustment in the transmission probabilities during the session . this excludes coordination among users , for example , using time division multiplexing . there is no cost of transmitting a packet . we formulate the medium access problem as a non - cooperative game to analyze the behavior of selfish users . we denote the set of users by @xmath0 . because we assume that a user uses the same transmission probability over the entire session , the strategy of a user is its transmission probability , and we denote the strategy of user @xmath1 by @xmath2 and the strategy space of user @xmath1 by @xmath3 $ ] for all @xmath4 . once the users decide their transmission probabilities , a strategy profile can be constructed . the users transmit their packets independently according to their transmission probabilities , and thus the strategy profile determines the probability of a successful transmission by user @xmath1 in a slot . a strategy profile can be written as a vector @xmath5 in @xmath6 , the set of strategy profiles . the payoff function of user @xmath1 , @xmath7 , is defined as @xmath8 where @xmath9 measures the value of transmission of user @xmath1 and @xmath10 is the probability of successful transmission by user @xmath1 . we define the _ contention game _ by the tuple @xmath11 . if the users choose their transmission probabilities taking others transmission probabilities as given , then the resulting outcome can be described by the solution concept of nash equilibrium @xcite . we first characterize the nash equilibria of the contention game . a strategy profile @xmath12 is a nash equilibrium of the contention game @xmath13 if and only if @xmath14 for at least one @xmath1 . _ * proof * _ : in the contention game , the best response correspondence of user @xmath1 assumes two sets : @xmath15 if @xmath16 and @xmath17 $ ] if @xmath18 . suppose that user @xmath1 chooses @xmath14 . then it is playing its best response while other users are also playing their best responses , which establishes the sufficiency part . to prove the necessity part , suppose that @xmath19 is a nash equilibrium and @xmath20 for all @xmath4 . since @xmath16 , @xmath2 is not a best response to @xmath21 , which is a contradiction . ' '' '' if a nash equilibrium @xmath19 has only one user @xmath1 such that @xmath14 , then @xmath22 and @xmath23 for all @xmath24 where @xmath25 can be as large as @xmath26 . if there are at least two users with the transmission probability equal to 1 , then we have @xmath27 for all @xmath4 . let @xmath28 , u_j = 0 \ ; \forall j \neq i \}$ ] . then , the set of nash equilibrium payoffs is given by @xmath29 given the game @xmath13 , we can define the _ set of feasible payoffs _ by @xmath30 a payoff profile @xmath31 in @xmath32 is _ pareto efficient _ if there is no other element @xmath33 in @xmath32 such that @xmath34 and @xmath35 for at least one user @xmath1 . we also call a strategy profile @xmath19 pareto efficient if @xmath36 is a pareto efficient payoff profile . let @xmath37 be the set of pareto efficient payoffs . there are @xmath38 points in @xmath39 , namely , @xmath31 such that @xmath40 and @xmath41 for all @xmath42 , for @xmath43 . these are the corner points of @xmath37 in which only one user receives a positive payoff . therefore , nash equilibrium payoff profiles are either inefficient or unfair . moreover , since @xmath14 is a _ weakly dominant strategy _ for every user @xmath1 , in a sense that @xmath44 for all @xmath45 , the most likely nash equilibrium is the one in which @xmath46 for all @xmath4 . at the most likely nash equilibrium , every user always transmits its packet , and as a result no packet is successfully transmitted . hence , the selfish behavior of the users is likely to lead to a network collapse , which gives zero payoff to every user , as argued also in @xcite . . ( a ) the set of feasible payoffs when coordination between two users is possible . ( b ) the set of nash equilibrium payoffs . ( c ) the set of feasible payoffs with independent transmission probabilities.,scaledwidth=100.0% ] figure 1 presents the payoff spaces of two homogeneous users with @xmath47 . if coordination between the two users is possible , they can achieve any payoff profile in the dark area of figure 1(a ) . for example , @xmath48 can be achieved by arranging user 1 to transmit only in odd - numbered slots and user 2 only in even - numbered slots . this kind of coordination can be supported through direct communications among the users or mediated communications . however , if such coordination is not possible and each user has to choose one transmission probability , nash equilibria yield the payoff profiles in figure 1(b ) . the set of feasible payoffs of the contention game is shown as the dark area of figure 1(c ) . the set of pareto - efficient payoff profiles is the frontier of that area . the lack of coordination makes the set of feasible payoffs smaller reducing the area of figure 1(a ) to that of figure 1(c ) . because the typical nash equilibrium payoff is @xmath49 , the next section develops a transformation of the contention game , and the set of equilibria of the resulting stackelberg game is shown to expand to the entire area of figure 1(c ) . we introduce a network manager as a special kind of user in the contention game and call him user 0 . as a user , the manager can access the channel with a certain transmission probability . however , the manager is different from the users in that he can choose his transmission probability depending on the transmission probabilities of the users . this ability of the manager enables him to act as the police . if the users access the channel excessively , the manager can intervene and punish them by choosing a high transmission probability , thus reducing the success rates of the users . formally , the strategy of the manager is an _ intervention function _ @xmath50 $ ] , which gives his transmission probability @xmath51 when the strategy profile of the users is @xmath19 . @xmath52 can be interpreted as the level of intervention or punishment by the manager when the users choose @xmath19 . note that the level of intervention by the manager is the same for every user . we assume that the manager has a specific `` target '' strategy profile @xmath53 , that his transmission has no value to him ( as well as to others ) , and that he is benevolent . one representation of his objective is the payoff function of the following form : @xmath54 this payoff function means that the manager wants the users to operate at the target strategy profile @xmath53 with the minimum level of intervention . we call the transformed game the _ stackelberg contention game _ because the manager chooses his strategy @xmath55 before the users make their decisions on the transmission probabilities . in this sense , the manager can be thought of as a stackelberg leader and the users as followers . the specific timing of the stackelberg contention game can be outlined as follows : 1 . the network manager determines his intervention function . 2 . knowing the intervention function of the manager , the users choose their transmission probabilities simultaneously . observing the strategy profile of the users , the manager determines the level of intervention using his intervention function . the transmission probabilities of the manager and the users determine their payoffs . timing 1 happens before the session starts . timing 2 occurs at the beginning of the session whereas timing 3 occurs when the manager knows the transmission probabilities of all the users . therefore , there is a time lag between the time when the session begins and when the manager starts to intervene . payoffs can be calculated as the probability of successful transmission averaged over the entire session , multiplied by valuation . if the interval between timing 2 and timing 3 is short relative to the duration of the session , the payoff of user @xmath1 can be approximated as the payoff during the intervention using the following payoff function : @xmath56 the transformation of the contention game into the stackelberg contention game is schematically shown in figure 2 . the figure shows that the main role of the manager is to set the intervention rule and to implement it . the users still behave non - cooperatively maximizing their payoffs , and the intervention of the manager affects their selfish behavior even though the manager does neither directly control their behavior nor continuously communicate with the users to convey coordination or price signals . in the stackelberg routing game of @xcite , the strategy spaces of the manager and a user coincide . if that is the case in the stackelberg contention game , i.e. , if the manager chooses a single transmission probability before the users choose theirs , then this intervention only makes the channel lossy but it does not provide incentives for users not to choose the maximum possible transmission probability . hence , in order to provide an incentive to choose a smaller transmission probability , the manager needs to vary his transmission probability depending on the transmission probabilities of the users . a stackelberg game is analyzed using a backward induction argument . the leader predicts the nash equilibrium behavior of the followers given his strategy and chooses the best strategy for him . the same argument can be applied to the stackelberg contention game . once the manager decides his strategy @xmath55 and commits to implement his transmission probability according to @xmath55 , the rest of the stackelberg contention game ( timing 24 ) can be viewed as a non - cooperative game played by the users . given the intervention function @xmath55 , the payoff function of user @xmath1 can be written as @xmath57 in essence , the role of the manager is to change the non - cooperative game that the users play from the contention game @xmath13 to a new game @xmath58 , which we call the _ contention game with intervention @xmath55_. understanding the non - cooperative behavior of the users given the intervention function @xmath55 , the manager will choose @xmath55 that maximizes his payoff . we now define an equilibrium concept for the stackelberg contention game . an intervention function of the manager @xmath55 and a profile of the transmission probabilities of the users @xmath59 constitutes a _ stackelberg equilibrium _ if ( i ) @xmath60 is a nash equilibrium of the contention game with intervention @xmath55 and ( ii ) @xmath61 and @xmath62 . combining ( i ) and ( ii ) , an equivalent definition is that ( @xmath63 is a stackelberg equilibrium if @xmath53 is a nash equilibrium of @xmath64 and @xmath65 . condition ( i ) says that once the manager chooses his strategy , the users will play a nash equilibrium strategy profile in the resulting game , and condition ( ii ) says that expecting the nash equilibrium strategy profile of the users , the manager chooses his strategy that achieves his objective . as we have mentioned earlier , the manager can choose only one level of intervention that affects the users equally . a question that arises is which strategy profile the manager can implement as a stackelberg equilibrium with one level of intervention for every user . we answer this question constructively . we propose a specific form of an intervention function with which the manager can attain any strategy profile @xmath53 with @xmath66 for all @xmath1 . the basic idea of this result is that because the strategy of the manager is not a single intervention level but a function whose value depends on the strategies of the users , he can discriminate the users by reacting differently to their transmission probabilities in choosing the level of intervention . therefore , even though the realized level of intervention is the same for every user , the manager can induce the users to choose different transmission probabilities . to construct such an intervention function , we first define the _ total relative deviation ( trd ) of @xmath19 from @xmath53 _ by @xmath67 since @xmath55 determines the transmission probability of the manager , its range should lie in @xmath68 $ ] . to satisfy this constraint , we define the _ trd - based intervention function _ by @xmath69_0 ^ 1\end{aligned}\ ] ] where the operator @xmath70_a^b = \min \ { \max\{x , a\ } , b\}$ ] is used to obtain the `` trimmed '' value of trd between 0 and 1 . the trd - based intervention can be interpreted in the following way . the manager sets the target at @xmath53 . as long as the users choose small transmission probabilities so that the trd of @xmath19 from @xmath53 does not exceed zero , the manager does not intervene . if it is larger than zero , the manager will respond to a one - unit increase in @xmath2 by increasing @xmath71 by @xmath72 units until the trd reaches 1 . the manager determines the degree of punishment based on the target transmission probability profile . if he wants a user to transmit with a low probability , then his punishment against its deviation is strong . [ prop1]proposition @xmath73 constitutes a stackelberg equilibrium . _ * proof * _ : we need to check two things . first , @xmath53 is a nash equilibrium of @xmath74 . second , @xmath75 . it is straightforward to confirm the second . to show the first , the payoff function of user @xmath1 given others strategies @xmath76 is @xmath77 it can be seen from the above expression that @xmath78 is increasing on @xmath79 , reaches a peak at @xmath80 , is decreasing on @xmath81 , and then stays at 0 on @xmath82 . therefore , user @xmath1 s best response to @xmath76 is @xmath83 for all @xmath1 , and thus @xmath53 constitutes a nash equilibrium of the contention game with trd - based intervention , @xmath74 . ' '' '' any feasible payoff profile @xmath84 of the contention game with @xmath85 for all @xmath4 can be achieved by a stackelberg equilibrium . corollary 1 resembles the folk theorem of repeated games @xcite in that it claims that any feasible outcome can be attained as an equilibrium . incentives not to deviate from a certain operating point are provided by the manager s intervention in the stackelberg contention game , while in a repeated game players do not deviate since a deviation is followed by punishment from other players . in proposition 2 , we have seen that @xmath53 is a nash equilibrium of the contention game with trd - based intervention . however , if other nash equilibria exist , the outcome may be different from the one that the manager intends . in fact , any strategy profile @xmath19 with @xmath14 for at least one @xmath1 is still a nash equilibrium of @xmath74 . the following proposition characterizes the set of nash equilibria of @xmath74 that are different from those of @xmath13 . [ prop1]proposition consider a strategy profile @xmath60 with @xmath86 for all @xmath4 . @xmath60 is a nash equilibrium of the contention game with trd - based intervention if and only if either @xmath87 or @xmath88 _ * proof * _ : see appendix a. ' '' '' transforming @xmath13 to @xmath74 does not eliminate the nash equilibria of the contention game . rather , the set of nash equilibria expands to include two classes of new equilibria . the first nash equilibrium of proposition 3 is the one that the manager intends the users to play . the second class of nash equilibria are those in which the sum of relative deviations of other users is already too large that no matter how small transmission probability user @xmath1 chooses , the level of intervention stays the same at 1 . since @xmath53 is chosen to satisfy @xmath89 for all @xmath1 and @xmath90 satisfies @xmath75 , it follows that @xmath91 for all @xmath1 . , we will use @xmath92 instead of @xmath93 when there is no confusion . ] for the second class of nash equilibria in proposition 3 , @xmath94 for all @xmath1 because @xmath95 . therefore , the payoff profile of the second class of nash equilibria is _ pareto dominated _ by that of the intended nash equilibrium in that the intended nash equilibrium yields a higher payoff for every user compared to the second class of nash equilibria . the same conclusion holds for nash equilibria with more than one user with transmission probability 1 because every user gets zero payoff . finally , the remaining nash equilibria are those with exactly one user with transmission probability 1 . suppose that @xmath96 . then the highest payoff for user @xmath1 is achieved when @xmath97 for all @xmath24 . denoting this strategy profile by @xmath98 , the payoff profile of @xmath98 is pareto dominated by that of @xmath53 if @xmath99 . we have seen that there are multiple nash equilibria of the contention game with trd - based intervention and that the nash equilibrium @xmath53 in general yields higher payoffs to the users than other nash equilibria . if the users are aware of the welfare properties of different nash equilibria , they will tend to select @xmath53 . suppose that the users play the second class of nash equilibria in proposition 3 for some reason . if the stackelberg contention game is played repeatedly and the users anticipate that the strategy profile of the other users will be the same as that of the last period , then it can be shown that under certain conditions there is a sequence of intervention functions convergent to @xmath90 that the manager can employ to have the users reach the intended nash equilibrium @xmath53 , thus approaching the stackelberg equilibrium . [ prop1]proposition suppose that at @xmath100 the manager chooses the intervention function @xmath90 and that the users play a nash equilibrium @xmath101 of the second class . without loss of generality , the users are enumerated so that the following holds : @xmath102 suppose further that for each @xmath1 , either @xmath103 or @xmath104 holds . at @xmath105 ; define @xmath106 assume that the manager employs the intervention function @xmath107_0 ^ 1 $ ] where @xmath108 and that user @xmath1 chooses @xmath109 as a best response to @xmath110 given @xmath111 . then @xmath112 for all @xmath43 and @xmath113 . _ * proof * _ : see appendix b. ' '' '' the reason that no user has an incentive to deviate from the second class of nash equilibria is that since others use high transmission probabilities , the trd is over 1 no matter what transmission probability a user chooses . since the punishment level is always 1 , a reduction of the transmission probability by a user is not rewarded by a decreased level of intervention . if the relative deviations of @xmath2 from @xmath83 are not too disperse , the manager can successively adjust down the effective range of punishment so that he can react to the changes in the strategies of the users . proposition 4 shows that this procedure succeeds to have the strategy profile of the users converge to the intended nash equilibrium . so far we have assumed that the manager has a target strategy profile @xmath53 and examined whether he can find an intervention function that implements it as a stackelberg equilibrium . this section discusses selection criteria that the manager can use to choose the target strategy profile . to address this issue , we rely on cooperative game theory because a reasonable choice of the manager should have a close relationship to the likely outcome of bargaining among the users if bargaining were possible for them @xcite . the absence of communication opportunities among the users prevents them from engaging in bargaining or from directly coordinating with each other . the pair @xmath114 is an _ n - person bargaining problem _ where @xmath115 is a closed and convex subset of @xmath116 , representing the set of feasible payoff allocations and @xmath117 is the disagreement payoff allocation . suppose that there exists @xmath118 such that @xmath119 for every @xmath1 . [ def1]definition @xmath120 is the _ nash bargaining solution _ for an n - person bargaining problem @xmath121 if it is the unique pareto efficient vector that solves @xmath122 consider the contention game @xmath13 . @xmath123 can be regarded as an @xmath38-person bargaining problem where @xmath32 is defined in ( [ eq : pay ] ) and @xmath124 is the disagreement point . the vector @xmath124 is the natural disagreement point because it is a nash equilibrium payoff as well as the minimax value for each user . the only departure from the standard theory is that the set of feasible payoffs @xmath32 is not convex . however , we can carry the definition of the nash bargaining solution to our setting as in @xcite . since the manager knows the structure of the contention game , he can calculate the nash bargaining solution @xmath31 for @xmath123 and find the strategy profile @xmath53 that yields @xmath31 . then the manager can implement @xmath53 by choosing @xmath90 based on @xmath53 . notice that the presence of the manager does not decrease the payoffs of the users because @xmath125 = 0 . the nash bargaining solution for @xmath123 has the following simple form . [ prop1]proposition @xmath126 is the nash bargaining solution for @xmath123 , and it is attained by @xmath127 for all @xmath43 . _ * proof * _ : the maximand in the definition of the nash bargaining solution can be written as @xmath128 since any @xmath84 satisfies @xmath129 , the above problem can be expressed in terms of @xmath19 : @xmath130 the logarithm of the objective function is strictly concave in @xmath19 , and the first - order optimality condition gives @xmath131 for all @xmath43 . ' '' '' the nash bargaining solution for @xmath123 treats every user equally in that it specifies the same transmission probability for every user . therefore , the manager does not need to know the vector of the values of transmission @xmath132 to implement the nash bargaining solution . the nash bargaining solution coincides with the kalai - smorodinsky solution @xcite because the maximum payoff for user @xmath1 is @xmath26 and the nash bargaining solution is the unique efficient payoff profile in which each user receives a payoff proportional to its maximum feasible payoff . if the manager wants to treat the users with discrimination , he can use the _ generalized nash product _ @xmath133 as the maximand to find a _ nonsymmetric nash bargaining solution _ , where @xmath134 represents the weight for user @xmath1 . one example of the weights is the valuation of the users . is private information , it would be interesting to construct a mechanism that induces users to reveal their true values @xmath26 . ] the nonsymmetric nash bargaining solution for @xmath123 can be shown to be achieved by @xmath135 for all @xmath1 using the similar method to the proof of proposition 5 . if some of the users can communicate and collude effectively , the network manager may want to choose a strategy profile which is self - enforcing even in the existence of coalitions . since we define a user as a transmitter - receiver pair , a collusion may occur when a single transmitter sends packets to several destinations and controls the transmission probabilities of several users . given the set of users @xmath136 , a _ coalition _ is any nonempty subset @xmath137 of @xmath138 . let @xmath139 be the strategy profile of the users in @xmath137 . [ def1]definition @xmath53 is _ coalition - proof _ with respect to a coalition @xmath137 in a non - cooperative game @xmath140^n,(u_i ) \rangle$ ] if there does not exist @xmath141^s$ ] such that @xmath142 for all @xmath143 and @xmath144 for at least one user @xmath143 . by definition , @xmath53 is coalition - proof with respect to the _ grand coalition _ @xmath145 if and only if @xmath146 is pareto efficient . if @xmath53 is a nash equilibrium , then it is coalition - proof with respect to any one - person `` coalition . '' the non - cooperative game of our interest is the contention game with trd - based intervention @xmath90 . [ prop1]proposition @xmath53 is coalition - proof with respect to a two - person coalition @xmath147 in the contention game with trd - based intervention @xmath90 if and only if @xmath148 . _ * proof * _ : see appendix c. ' '' '' the proof of proposition 6 shows that if @xmath149 then users @xmath1 and @xmath150 can jointly reduce their transmission probabilities to increase their payoffs at the same time . for example , suppose that users 1 and 2 are controlled by the same transmitter and that the manager selects the target @xmath53 with @xmath151 and @xmath152 . then @xmath153 and @xmath154 . suppose that the two users jointly deviate to @xmath155 . then the new payoffs are @xmath156 and @xmath157 , which is strictly better for both users . a decrease in @xmath2 and @xmath158 at the same time also increases the payoffs of all the users not belonging to the coalition , which implies that a target @xmath53 with @xmath159 is not pareto efficient . this observation leads to the following corollary . [ corr1]corollary if @xmath53 is pareto efficient in the contention game with trd - based intervention @xmath90 , then it is coalition - proof with respect to any two - person coalition . in fact , we can generalize the above corollary and provide a stronger statement . [ prop1]proposition @xmath53 is pareto efficient in the contention game with trd - based intervention @xmath90 if and only if it is coalition - proof with respect to any coalition . _ * proof * _ : see appendix d. ' '' '' we have introduced and analyzed the contention game and the stackelberg contention game with trd - based intervention . in this section we discuss what the players of each game need to know in order to play the corresponding equilibrium . in a general non - cooperative game , each user needs to know , or predict correctly , the strategy profile of others in order to find its best response strategy . in the contention game with the payoff function @xmath160 , it suffices for user @xmath1 to know the sign of @xmath161 , i.e. , whether it is positive or zero , to calculate its best response . on the other hand , @xmath14 is a _ weakly dominant strategy _ for any user @xmath1 , which means setting @xmath14 is weakly better no matter what strategies other users choose . hence , the nash equilibrium @xmath162 does not require any knowledge on others strategies . considering the timing of the stackelberg contention game outlined in section 3 , we can list the following requirements on the manager and the users for the stackelberg equilibrium to be played . * requirement m. * once the users choose the transmission probabilities , the manager observes the strategy profile of the users . the manager needs to decide the level of intervention as a function of the transmission probabilities of the users . if the manager can distinguish the access of each user and have sufficiently many observations to determine the transmission probability of each user , then this requirement will be satisfied . if the manager can observe the channel state ( idle , success , collision ) and identify the users of successfully transmitted packets , he can estimate the transmission probability of each user in the following way . first , he can obtain an estimate of @xmath163 by calculating the frequency of idle slots , called @xmath164 . second , he can obtain an estimate of @xmath10 by calculating the frequency of slots in which user @xmath1 succeeds to transmit its packet , called @xmath165 . finally , an estimate of @xmath2 can be obtained by solving @xmath166 for @xmath2 . * requirement u. * user @xmath1 knows @xmath90 ( and thus @xmath53 ) and @xmath21 when it chooses its transmission probability . requirement u is sufficient for the nash equilibrium of the contention game with trd - based intervention to be played by the users . user @xmath1 can find its best response strategy by maximizing @xmath167 given @xmath90 and @xmath21 . in fact , a weaker requirement is compatible with the nash equilibrium of the contention game with trd - based intervention . suppose that user @xmath1 knows the _ form _ of intervention function @xmath90 and the value of @xmath83 , and observes the intervention level @xmath71 . @xmath53 embedded in the trd - based intervention function @xmath90 can be thought of as a recommended strategy profile by the manager ( thus the communication from the manager to the users occurs indirectly through the function @xmath90 ) . even though user @xmath1 does not know the recommended strategies to other users , i.e. , the values of @xmath168 , @xmath24 , it knows its recommended transmission probability . from the form of the intervention function , user @xmath1 can derive that it is of its best interest to follow the recommendation as long as all the other users follow their recommended strategies . observing @xmath169 confirms its belief that other users play the recommended strategies , and it has no reason to deviate . the users can acquire knowledge on the intervention function @xmath90 through one of three ways : ( i ) known protocol , ( ii ) announcement , and ( iii ) learning . the first method is effective in the case where a certain network manager operates in a certain channel ( for example , a frequency band ) . the community of users will know the protocol ( or intervention function ) used by the manager . this method does not require any information exchange between the manager and the users . neither teaching of the manager nor learning of the users is necessary . however , there is inflexibility in choosing an intervention function , and the manager can not change his target strategy profile frequently . nevertheless , this is the method most often used in current wireless networks , where users appertain to a predetermined class of known and homogeneous protocols . the second method allows the manager to make the users know @xmath90 directly , which includes information on the target @xmath53 . the manager will execute his intervention according to the announced intervention function because the stackelberg equilibrium @xmath73 achieves his objective however , it requires explicit message delivery from the manager to the users , which is sometimes costly or may even be impossible in practice . finally , if the stackelberg contention game is played repeatedly with the same intervention function , the users may be able to recover the form of the intervention function chosen by the manager based on their observations on @xmath170 , for example , using learning techniques developed in @xcite . however , this process may take long and the users may not be able to collect enough data to find out the true functional form if there is limited experimentation of the users . _ if users are obedient , the manager can use centralized control by communicating @xmath83 to user @xmath1 . additional communication and estimation overhead required for the stackelberg equilibrium can be considered as a cost incurred to deal with the selfish behavior of users , or to provide incentives for users to follow @xmath53 . the construction of the trd - based intervention function assumes that the manager can observe or estimate the transmission probabilities of the users correctly . in real applications , the manager may not be able to observe the exact choice made by each user . we consider several scenarios under which the manager has limited observability and examine how the trd - based intervention function can be modified in those scenarios . let @xmath171 be a set of intervals which partition @xmath68 $ ] . we assume that each interval contains its right end point . for simplicity , we will consider intervals of the same length . that is , @xmath172 , \left(\frac{1}{m } , \frac{2}{m}\right ] , \ldots , \left(\frac{m-1}{m } , 1 \right ] \right\}$ ] , and we call @xmath173 and @xmath174 $ ] for all @xmath175 . suppose that the manager only observes which interval in @xmath176 each @xmath2 belongs to . in other words , the manager observes @xmath177 instead of @xmath2 such that @xmath178 . in this case , the level of intervention is calculated based on @xmath179 rather than @xmath19 . it means that given @xmath21 , @xmath71 would be the same for any @xmath180 if @xmath2 and @xmath181 belong to the same @xmath182 . since any @xmath183 is weakly dominated by @xmath184 , the users will choose their transmission probabilities at the right end points of the intervals in @xmath176 . this in turn will affect the choice of a target by the manager . the manager will be restricted to choose @xmath53 such that @xmath185 for all @xmath4 . then the manager can implement @xmath53 with the intervention function @xmath186 , where @xmath2 is set equal to @xmath187 . in summary , the quantized observation on @xmath19 restricts the choice of @xmath53 by the manager from @xmath188 to @xmath189 . . ( b ) @xmath190 . , scaledwidth=70.0% ] figure 3 shows the payoff profiles that can be achieved by the manager with quantized observation . when the number of intervals is moderately large , the manager has many options near or on the pareto efficiency boundary . we modify the stackelberg contention game to analyze the case where the manager observes noisy signals of the transmission probabilities of the users . let @xmath191 $ ] be the strategy space of user @xmath1 , where @xmath192 is a small positive number . we assume that the users can observe the strategy profile @xmath19 , but the manager observes a noisy signal of @xmath19 . the manager observes @xmath193 instead of @xmath2 where @xmath193 is uniformly distributed on @xmath194 $ ] , independently over @xmath4 . suppose that the manager chooses a target @xmath53 such that @xmath195 $ ] . the expected payoff of user @xmath1 when the manager uses an intervention function @xmath55 is @xmath196 = k_i p_i \prod_{j \neq i } ( 1-p_j ) \left(1 - e[g(\mathbf{p}^o)|\mathbf{p } ] \right).\end{aligned}\ ] ] hence , the intervention function is effectively @xmath197 $ ] instead of @xmath52 when the manager observes @xmath198 . if @xmath60 is a nash equilibrium of the contention game with intervention @xmath55 when @xmath19 is perfectly observable to the manager and @xmath197 = g(\mathbf{p})$ ] for all @xmath19 such that @xmath199 , then @xmath60 will still be a nash equilibrium of the contention game with intervention @xmath55 when the manager observes a noisy signal of the strategy profile of the users . consider the trd - based intervention function @xmath90 . since @xmath200 for all @xmath12 and @xmath201 with a positive probability when @xmath202 , @xmath203 > 0 $ ] whereas @xmath75 . since @xmath90 is kinked at @xmath53 , the noise in @xmath198 will distort the incentives of the users to choose @xmath53 . the manager can implement his target @xmath53 at the expense of intervention with a positive probability . if the manager adopts the following intervention function @xmath204 where @xmath205 , then @xmath53 is a nash equilibrium of the contention game with intervention @xmath55 , but the average level of intervention at @xmath53 is @xmath206 = g(\tilde{\mathbf{p } } ) = \frac{\epsilon q}{1 + \epsilon q } > 0,\end{aligned}\ ] ] which can be thought of as the efficiency loss due to the noise in observations . . ( b ) @xmath207 . , scaledwidth=70.0% ] figure 4 illustrates the set of payoff profiles that can be achieved with the intervention function given by ( [ eq : modtrd ] ) . as the size of the noise gets smaller , the set expands to approach the pareto efficiency boundary . we consider the case where the manager can observe only the frequency of the slots that are not accessed by any user . if the users transmit their packets according to @xmath19 , then the manager observes only the aggregate probability @xmath208 . in this scenario , the intervention function that the manager chooses has to be a function of @xmath163 , and this implies that the manager can not discriminate among the users . the trd - based intervention function @xmath90 allows the manager to use different reactions to each user s deviation . in the effective region where the trd is between 0 and 1 , one unit increase in @xmath2 results in @xmath72 units increase in @xmath71 . however , this kind of discrimination through the structure of the intervention function is impossible when the manager can not observe individual transmission probabilities . this limitation forces the manager to treat the users equally , and the target has to be chosen such that @xmath209 for all @xmath4 . if the manager uses the following intervention function , @xmath210_0 ^ 1\end{aligned}\ ] ] then he can implement @xmath211 with @xmath65 as a stackelberg equilibrium . hence , if the manager only observes the aggregate probability , this prevents him from setting the target transmission probabilities differently across users . . ( b ) heterogeneous users with @xmath212 and @xmath213.,scaledwidth=70.0% ] figure 5 shows the payoff profiles achieved with symmetric strategy profiles , which can be implemented by the manager who observes the aggregate probability . we now relax requirement u and assume that user @xmath1 can observe only the aggregate probability @xmath214 . even though the users do not know the exact form of the intervention function of the manager , they are aware of the dependence of @xmath71 on their transmission probabilities and try to model this dependence based on their observations @xmath215 . specifically , user @xmath1 builds a conjecture function @xmath216 \rightarrow [ 0,1]$ ] , which means that user @xmath1 conjectures that the value of @xmath214 will be @xmath217 if he chooses @xmath2 . the equilibrium concept appropriate in this context is _ conjectural equilibrium _ first introduced by hahn @xcite . [ def1]definition a strategy profile @xmath60 and a profile of conjectures @xmath218 constitutes a _ conjectural equilibrium _ of the contention game with intervention @xmath55 if @xmath219 and @xmath220 for all @xmath4 . the first condition states that @xmath221 is optimal given user @xmath1 s conjecture @xmath222 , and the second condition says that its conjecture is consistent with its observation . it can be seen from this definition that the conjectural equilibrium is a generalization of nash equilibrium in that any nash equilibrium is a conjectural equilibrium with every user holding the correct conjecture given others strategies . on the other hand , it is quite general in some cases , and in the game we consider , for any strategy profile @xmath223 , there exists a conjecture profile @xmath224 that constitutes a conjectural equilibrium . for example , we can set @xmath225 if @xmath226 and 0 otherwise . since the trd - based intervention function @xmath90 is linear in each @xmath2 , it is natural for the users to adopt a conjecture function of the linear form . let us assume that conjecture functions are of the following trimmed linear form : @xmath227_0 ^ 1\end{aligned}\ ] ] for some @xmath228 . we say that a conjecture function @xmath222 is _ linearly consistent _ at @xmath60 if it is locally correct up to the first derivative at @xmath60 , i.e. , @xmath229 and @xmath230 . since the trd - based intervention function @xmath90 is linear in each @xmath2 , the conjecture function @xmath231 is linearly consistent at @xmath53 , and @xmath53 and @xmath232 constitutes a conjectural equilibrium . therefore , as long as the users use linearly consistent conjectures , limited observability of the users does not affect the final outcome . to build linearly consistent conjectures , however , the users need to experiment and collect data using local deviations from the equilibrium point in a repeated play of the stackelberg contention game . a loss in performance may result during this learning phase . we assume that the users are homogeneous with @xmath233 for all @xmath234 . given a transmission probability profile @xmath235 , the system utilization ratio can be defined as the probability of successful transmission in a given slot @xmath236 note that the maximum system utilization ratio is 1 , which occurs when only one user transmits with probability 1 while others never transmit . table 1 shows the individual payoffs and the system utilization ratios for the number of users 3 , 10 , and 100 when the manager implements the target at the symmetric efficient strategy profile @xmath237 . [ cols="^,^,^",options="header " , ] table 2 . average individual payoffs , aggregate payoffs , standard deviations of individual payoffs , system utilization ratios , nash products , and generalized nash products with heterogeneous users table 2 shows that a tradeoff between efficiency ( measured by the sum of payoffs ) and equity exists when users are heterogeneous . a higher aggregate payoff is achieved when users with high valuations are given priority . at the same time , it limits access by users with low valuations , which increases variations in individual payoffs . also , the results in table 2 are consistent with that @xmath238 is a nash bargaining solution and that @xmath239 is a nonsymmetric nash bargaining solution with weights equal to valuations . we have analyzed the problem of multiple users who share a common communication channel . using the game theory framework , we have shown that selfish behavior is likely to lead to a network collapse . however , full system utilization requires coordination among users using explicit message exchanges , which may be impractical given the distributed nature of wireless networks . to achieve a better performance without coordination schemes , users need to sustain cooperation . we provide incentives for selfish users to limit their access to the channel by introducing an intervention function of the network manager . with trd - based intervention functions , the manager can implement any outcome of the contention game as a stackelberg equilibrium . we have discussed the amount of information required for implementation , and how the various kinds of relaxations of the requirements affect the outcome of the stackelberg contention game . our approach of using an intervention function to improve network performance can be applied to other situations in wireless communications . potential applications of the idea include sustaining cooperation in multi - hop networks and limiting the attack of adversary users . an intervention function may be designed to serve as a coordination device in addition to providing selfish users with incentives to cooperate . finally , designing a protocol that enables users to play the role of the manager in a distributed manner will be critical to ensure that our approach can be adopted in completely decentralized communication scenarios , where no manager is present . recall @xmath240 used to define @xmath241 . we examine whether a strategy profile @xmath60 with @xmath86 for all @xmath4 constitutes a nash equilibrium of @xmath74 by considering four cases on the value of @xmath242 . * @xmath243 . let @xmath244 . if user @xmath1 changes its transmission probability from @xmath221 to @xmath245 , then its payoff increases because @xmath71 is still zero . hence @xmath60 can not be a nash equilibrium if @xmath243 . * case 2 . * @xmath246 . consider arbitrary user @xmath1 . if it deviates to @xmath247 , @xmath71 is still zero and @xmath167 decreases . @xmath248 is differentiable and strictly concave on @xmath249 . since @xmath250 , @xmath251 and @xmath86 for all @xmath1 , @xmath252 there is no gain for user @xmath1 from deviating to any @xmath253 if and only if @xmath254 , which is equivalent to @xmath255 . for @xmath60 to be a nash equilibrium , we need @xmath256 for all @xmath43 . to satisfy @xmath246 , all inequalities should be equalities . hence , only @xmath257 is a nash equilibrium among @xmath60 such that @xmath246 . * case 3 . * @xmath258 . since @xmath259 , there is no gain for user @xmath1 to deviate to @xmath2 such that @xmath260 . if there is a gain from deviation to @xmath2 such that @xmath261 , then there is another profitable deviation @xmath181 such that @xmath262 by using the argument of case 1 . therefore , we can restrict our attention to deviations @xmath2 that lead to @xmath263 . at such a deviation by user @xmath1 , @xmath264 @xmath221 is best response to @xmath265 if and only if @xmath266 . using the first derivative given in case 2 , we obtain @xmath267 for @xmath60 to be a nash equilibrium , the above inequality should be satisfied for every @xmath1 , which in turn implies @xmath268 and this contradicts to the initial assumption @xmath269 . therefore , there is no @xmath60 with @xmath258 that constitutes a nash equilibrium . * @xmath270 . since @xmath94 for every @xmath1 , there is a profitable deviation of user @xmath1 only if there exists @xmath271 such that @xmath272 . equivalently , if setting @xmath273 yields @xmath274 , then there is no profitable deviation of user @xmath1 from @xmath221 . since @xmath275 @xmath276 with @xmath270 is a nash equilibrium if and only if @xmath277 consider @xmath278 . user @xmath1 chooses @xmath279 to maximize @xmath280 if @xmath281 , the maximum is attained at @xmath279 that satisfies @xmath282 notice that @xmath283 . if @xmath284 , then @xmath285 for all @xmath286 . since any @xmath2 is a best response in this case , we assume that @xmath287 . is chosen according to ( [ eq : aaa ] ) , we do not need the assumption that for each @xmath1 either @xmath288 or @xmath104 in the proposition . ] consider @xmath289 . first , consider user @xmath1 such that @xmath103 . since @xmath290 , @xmath291 . using an analogous argument , we get @xmath292 next consider user @xmath1 such that @xmath293 . since @xmath294 , we again have @xmath295 and the best response is given by @xmath296 considering a general @xmath297 , we get @xmath298 for user @xmath1 such that @xmath288 and @xmath299 for user @xmath1 such that @xmath104 . taking limits as @xmath300 , we obtain the conclusions of the proposition . suppose that the users in the coalition @xmath301 choose @xmath302 instead of @xmath303 . then @xmath304 and @xmath305 hence , @xmath53 is coalition - proof with respect to @xmath137 if and only if there does not exist @xmath306 ^ 2 $ ] such that @xmath307 with at least one inequality strict . first , notice that setting @xmath80 and @xmath308 will violate one of the two inequalities . the inequality for user @xmath1 will not hold if @xmath309 , and the one for user @xmath150 will not hold if @xmath310 . hence , both @xmath311 and @xmath308 are necessary to have both inequalities satisfied at the same time . we consider four possible cases . * case 1 . * @xmath79 and @xmath309 since @xmath312 , ( [ eq : useri ] ) is violated . * case 2 . * @xmath313 and @xmath314 equation ( [ eq : userj ] ) is violated . * case 3 . * @xmath79 and @xmath314 since @xmath315 , @xmath316 . hence , ( [ eq : useri ] ) and ( [ eq : userj ] ) become @xmath317 we consider the contour curves of @xmath318 and @xmath319 going through @xmath303 in the @xmath320-plane . the slope of the contour curve of @xmath321 at @xmath303 is @xmath322 and that of @xmath323 is @xmath324 . there is no area of mutual improvement if and only if @xmath325 which is equivalent to @xmath326 . * @xmath313 and @xmath309 since @xmath327 , @xmath328 as long as @xmath329 . hence , ( [ eq : useri ] ) and ( [ eq : userj ] ) become @xmath330 the slope of the contour curve of @xmath331 at @xmath303 is @xmath332 and that of @xmath333 is @xmath334 therefore , there is no @xmath335 that satisfies ( [ eq : useri ] ) and ( [ eq : userj ] ) at the same time . the `` if '' part is trivial because a strategy profile that is coalition - proof with respect to the grand coalition is pareto efficient . to establish the `` only if '' part , we will prove that if for a given strategy profile there exists a coalition that can improve the payoffs of its members then its deviation will not hurt other users outside of the coalition , which shows that the original strategy profile is not pareto efficient . consider a strategy profile @xmath53 and a coalition @xmath336 that can improve upon @xmath53 by deviating from @xmath337 to @xmath139 . let @xmath338 the transmission probability of the manager after the deviation by coalition @xmath137 . since choosing @xmath139 instead of @xmath337 yields higher payoffs to the members of @xmath137 , we have @xmath339 for all @xmath143 with at least one inequality strict . we want to show that the members not in the coalition @xmath137 do not get lower payoffs as a result of the deviation by @xmath137 , that is , @xmath340 suppose @xmath341 . we can see that @xmath342 and @xmath343 for all @xmath143 because the right - hand side of ( [ eq : coal ] ) is strictly positive . combining this inequality with ( [ eq : coal ] ) yields @xmath344 for all @xmath143 , which implies @xmath345 . we can write @xmath346 for some @xmath347 for @xmath143 . then @xmath348 . ( [ eq : coal ] ) can be rewritten as @xmath349 for all @xmath143 . simplifying this gives @xmath350 for all @xmath143 . summing these inequalities up over @xmath143 , we get @xmath351 where @xmath352 is the number of the members in @xmath137 . this inequality simplifies to @xmath353 , which is a contradiction . 99 j .- w . lee , a. tang , j. huang , m. chiang , and a. r. calderbank , `` reverse - engineering mac : a non - cooperative game model , '' _ ieee journal on selected areas in communications _ 25 , no . 6 , pp . 11351147 , 2007 . g. tan and j. guttag , `` the 802.11 mac protocol leads to inefficient equilibria , '' in _ proceedings of the 24th annual joint conference of the ieee computer and communications societies ( infocom 2005 ) _ , vol . 1 , pp . 111 , miami , fl , usa , march 2005 . r. t. ma , v. misra , and d. rubenstein , `` modeling and analysis of generalized slotted - aloha mac protocols in cooperative , competitive and adversarial environments , '' in _ proceedings of the 26th ieee international conference on distributed computing systems ( icdcs 06 ) _ , lisboa , portugal , july 2006 . y. jin and g. kesidis , `` a pricing strategy for an aloha network of heterogeneous users with inelastic bandwidth requirements , '' in _ proceedings of the 39th annual conference on information sciences and systems _ , princeton , nj , usa , march 2002 . d. wang , c. comaniciu , and u. tureli , `` a fair and efficient pricing strategy for slotted aloha in mpr models , '' in _ proceedings of the 64th ieee vehicular technology conference _ , pp . 24742478 , montral , canada , september 2006 . m. bloem , t. alpcan , and t. baar , `` a stackelberg game for power control and channel allocation in cognitive radio networks , '' in _ proceedings of the 1st international workshop on game theory in communication networks ( gamecomm2007 ) _ , nantes , france , october 2007 . l. chen , t. cui , s. h. low , and j. c. doyle , `` a game - theoretic model for medium access control , '' in _ proceedings of the 3rd international wireless internet conference _ , austin , tx , usa , october 2007 . l. chen , s. h. low , and j. c. doyle , contention control : a game - theoretic approach , in _ proceedings of the 46th ieee conference on decision and control _ , pp . 34283434 , new orleans , la , usa , december 2007 . a. h. mohsenian - rad , j. huang , m. chiang , and v. w. s. wong , `` utility - optimal random access without message passing , '' _ ieee transactions on wireless communications _ , vol . 8 , no . 3 , pp . 10731079 , 2009 . m. agalj , s. ganeriwal , i. aad , and j .- hubaux , `` on selfish behavior in csma / ca networks , '' in _ proceedings of the 24th annual joint conference of the ieee computer and communications societies ( infocom 2005 ) _ , vol . 4 , pp . 25132524 , miami , fl , usa , march 2005 . j. hu and m. p. wellman , `` online learning about other agents in a dynamic multiagent system , '' in _ proceedings of the 2nd international conference on autonomous agents _ , pp . 239246 , minneapolis , mn , usa , may 1998 .

interactions among selfish users sharing a common transmission channel can be modeled as a non - cooperative game using the game theory framework . when selfish users choose their transmission probabilities independently without any coordination mechanism , nash equilibria usually result in a network collapse . we propose a methodology that transforms the non - cooperative game into a stackelberg game . stackelberg equilibria of the stackelberg game can overcome the deficiency of the nash equilibria of the original game . a particular type of stackelberg intervention is constructed to show that any positive payoff profile feasible with independent transmission probabilities can be achieved as a stackelberg equilibrium payoff profile . we discuss criteria to select an operating point of the network and informational requirements for the stackelberg game . we relax the requirements and examine the effects of relaxation on performance .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Trauma Institute Research Program Act''. SEC. 2. FINDINGS. Congress finds the following: (1) Wars have always generated technological and medical advances. (2) Trauma is the number one killer of the Nation's fighting soldiers, having caused over 30,000 injuries and over 4,000 deaths in the Global War on Terror. (3) In the United States, civilian trauma is the leading cause of death from ages 1 to 44 and is responsible for over 160,000 deaths annually. (4) Each year trauma accounts for 37 million emergency department visits and 2.6 million hospital admissions. (5) Trauma is a disease affecting all ages of people, and the impact of life years lost is 4 times greater than heart disease or cancer. (6) Injuries in a single year will ultimately cost the United States $406 billion, with $326 billion in lost productivity and $80.2 billion in medical costs (representing approximately 6 percent of total annual health expenditures). (7) Injury accounts for 4 of the top ten causes of death and disability-adjusted life years lost worldwide. (8) While the mechanisms of injury are different, military and civilian trauma casualties are treated similarly, thus improvements gained by focused, relevant trauma research in each group will benefit both. (9) Despite these alarming facts, within the context of years of potential life lost, the National Institutes of Health support ratio for HIV is $3.51, for cancer is $1.65, and for trauma is $0.10 cents. (10) Despite a mandate to promote research directed toward specific health issues relevant to the military forces, the Peer Reviewed Medical Research Program within the Congressionally Directed Medical Research Programs has spent less than a third of funding on trauma research. (11) The National Trauma Institute (NTI) in San Antonio, Texas, is a not-for-profit research institute formed by military-civilian collaboration between Wilford Hall Medical Center, San Antonio, Texas; University Hospital; the University of Texas Health Science Center, San Antonio, Texas; and Brooke Army Medical Center, San Antonio, Texas. NTI can build on the military-civilian collaboration to fill the gap in trauma research by setting a comprehensive research agenda to award grants to the best researchers in the country. (12) NTI, as a consortium of civilian and Department of Defense centers, is the natural starting point to translate battlefield innovations to civilians at home. (13) NTI, as a centralized institute to coordinate a national trauma research agenda, will substantially reduce the number of injuries and deaths to the Nation's soldiers on the battlefield and civilians at home. SEC. 3. ESTABLISHMENT. (a) Establishment.--The Secretary of Defense shall establish a National Trauma Institute Research Program at the National Trauma Institute as a military-civilian public-private partnership to nationally fund trauma research. (b) Purposes.--The purposes of the National Trauma Institute Research Program shall be-- (1) to develop and implement revolutionary medical technologies to improve injury prevention and diagnosis, survival, and quality of life for victims of trauma and burn injury; (2) to implement a national multidisciplinary, multi-center collaborative research effort; and (3) to create and administer a competitive, peer-reviewed trauma research grant program that supports research that includes, at a minimum, the following: (A) Injury prevention and education. (B) Improved prehospital and inter-hospital triage. (C) Resuscitation. (D) Early, effective treatment of compressible and non-compressible bleeding. (E) Improved burn care. (F) Head and spinal cord injury. (G) Tissue engineering and regenerative medicine. (H) Orthopedics. (I) Improved intensive care unit treatment and management. (J) Enhanced rehabilitation and recovery. (K) Trauma care systems. (L) Outcomes. SEC. 4. AUTHORIZATION OF APPROPRIATIONS. There is authorized to be appropriated to the Secretary of Defense $25,000,000 for the first fiscal year beginning after the date of the enactment of this Act for purposes of carrying out the activities of the National Trauma Institute Research Program as described in this Act. Such funds shall not be available for general administrative expenses of the Secretary of Defense.

National Trauma Institute Research Program Act - Directs the Secretary of Defense to establish a National Trauma Institute Research Program at the National Trauma Institute as a military-civilian public-private partnership to nationally fund trauma research.

Only a few minutes ago, the entire music industry stood on a stage in a collective display of how rich and out of touch they are. They think you are willing to pay up to double the price of other streaming music services to pay for their streaming music service, because they are crazy. Imagine this: canceling your Spotify subscription, and paying $20 for a Tidal subscription instead. It's more expensive because it's "higher quality" and "artist-owned," which is important because Usher, Daft Punk, and Madonna have been living in wretched penury for far too long, and it's time for people to give back. The modern-day Our Gang (which counted among its members not only the aforementioned supernovas, but also Rihanna, Nicki Minaj, Kanye West, Chris Martin, and Jack White) held a "keynote" to promote Tidal, the already extant European streaming company Jay Z recently purchased for $56 million because he's bored. Jay Z and Beyonce (also present, beaming) dug up an old email thread (SUBJ: SURPRISE BRUNCH PARTY SATURDAY!), hit reply-all, and look at how many of their family friends turned out to stand on stage, visibly uncomfortable, and listen to Alicia Keys give an incoherent speech. At the conclusion of Keys' statement, which merged the rarely combined traits of being about an app and quoting Nietzsche, the artists all signed some sort of "declaration" one by one. I don't know what the document said—it was probably just a blank piece of paper, or perhaps an original copy of the Declaration of Independence that Deadmau5 received as a White Elephant gift. When it came time for Madonna to sign, she put her whole leg up on the table, as if to say to the world World, I'm MADONNA and yes I am not too old to move my leg this way. No one is going to use Tidal. These dummies! In case you had any lingering sympathy for the struggling mega-famous recording artist, here's a video they made to make you hate them: "We're going to change the course of history," Jay Z says on camera. Then he and his friends raise a champagne toast to the glorious future. ||||| Tidal, the high-definition music streaming service acquired by rapper and music mogul Jay-Z, is gearing up for its official relaunch under new ownership later today, and it will be doing so by reportedly making a move to snag new releases by some of the biggest musicians of the moment including Kanye West, Madonna and Daft Punk, ahead of rival services like Spotify and Beats. The company has been sending out invites for a press conference being held at 5pm Eastern time today, in which Shawn “Jay-Z” Carter “will announce a commitment to a new direction for the music industry from both a creative and business perspective.” While there is not much detail being provided officially, unofficially we’ve heard that the company will be using the event to confirm the first big-name artists to stream music exclusively on the Tidal platform. What might those artists be doing on Tidal? Not an ordinary streaming deal, it seems. Over the weekend, the Swedish blog Breakit reported — citing sources close to the deal — that Tidal’s plan of attack will be to ink first-window deals with the artists, where Tidal would get first releases of tracks from big-name artists ahead of any other digital streaming services. This would be exclusive, but only for a period: Spotify, Deezer and others would eventually also get these tracks, but only later. This is not unlike how services like Netflix often get films after they have gone through cinema and DVD release windows, and subsequently what Vessel is trying to do to upend that. For those of you who browse social networks or follow music news, the list of artists gathering around Tidal shouldn’t come as too much of a surprise: a swathe of big-name musicians — including Madonna, Kanye West, Beyonce, Arcade Fire, Calvin Harris and others are using the #tidalforall hashtag on sites like Twitter and Instagram, as well as sending out messages or just changing their profile to a turquoise blue color to support the service. It’s a pretty strong bet that the artists that all started sending these out around midnight Eastern time will be among those involved in some way in the news today. It would also follow on the heels of Taylor Swift’s catalog coming to Tidal last week — minus her 1989 album. This is not an exclusive deal but lays the groundwork for other Swift music to make its way to Tidal first. What’s the pull for these artists? It’s partly the Jay-Z connection. His Roc Nation agency works with a long list of musicians to provide publishing, management, label and other services, with Tidal becoming yet another string on Roc Nation’s bow as a one-stop music distribution shop. On the other hand, from what we understand, Tidal is also offering a more attractive set of terms to musicians than other streaming services — often agreeing to payouts of twice as much as its rivals. (We’ve asked to see if we can get more concrete numbers to support the claim.) With many artists complaining that digital music is not providing decent enough returns, the later of these could be a deal maker for Tidal. The big question is whether artists are willing to make the bet on payouts-per-stream over that of visibility: right now Tidal has only 35,000 subscribers paying $19.99 per month across the markets in which it is active, which include the U.S. and UK. By comparison, Spotify noted 15 million paying subscribers in January of this year. Tidal also offers a standard definition service at $9.99. While Jay-Z won agreement this month from Aspiro shareholders to buy Tidal for $54 million, the shares are not due to transfer until mid-April, we understand. ||||| Musicians including Beyoncé and Madonna show support for rapper as he overhauls service designed to make more money for artists He has sold 100m records, founded a business empire worth upwards of $520m (£350m) and married Beyoncé. Now, Jay Z, backed by a roll call of A-list friends, is fronting the relaunch of a music streaming website heralded as the first real challenger to Spotify. Kanye West, Rihanna, Coldplay, Madonna, Alicia Keys, Beyoncé and more threw their weight behind the rapper at a press ­conference last night where he unveiled the new look for Tidal, a streaming site originally launched by Norwegian firm Aspiro in October 2014 and acquired for $56m earlier this month by a company controlled by the music mogul. It is planned that Tidal will compete with Spotify and upcoming streaming services from Apple and YouTube by offering exclusive music from prominent artists, including studio sessions and demo tracks, while giving them new ways to communicate with fans. Musicians including Beyoncé, Deadmau5, Nicki Minaj and Jack White replaced their Twitter profile pictures with blank blue images while tweeting the #TIDALforALL hashtag ahead of the event in a show of online support. “Together, we can turn the tide and make music history. Start by turning your profile picture blue,” Kanye West tweeted ahead of the event. Alicia Keys described Tidal as “the first artist-owned global music and entertainment platform” and promised to “create a better service and a better experience for both fans and artists … where we will deliver exclusive experiences that cannot be found anywhere else”. Tidal’s key selling point so far has been its “lossless” quality streams, for which the company charges a monthly subscription of £19.99 – double its rivals. It is available in 31 countries, with six more to follow by the end of June. By the end of 2014, Tidal had 500,000 paying users. It will launch a £9.99 subscription model alongside its existing one. Under Jay Z, Tidal’s strategy will include encouraging artists to lobby their labels to “window” new releases for at least a week, meaning they will be exclusive to Tidal for that period. He told Billboard: “We didn’t like the direction music was going and thought maybe we could get in and strike an honest blow. Will artists make more money? Even if it means less profit for our bottom line, absolutely. That’s easy for us. We can do that. Less profit for our bottom line, more money for the artist; fantastic.” The company is not alone in this desire. Apple is planning to relaunch its currently US-only Beats Music streaming service worldwide later in 2015, and has been courting artists and labels intensely to secure exclusives. With Google also waving its own chequebook – it struck a deal for a month-long exclusive on Take That’s latest album for its Google Play Music service in November 2014 – there is set to be a bidding war for new albums by prominent artists. Spotify has signed its own exclusives in the past with artists including ­Metallica and Led Zeppelin, and remains ­defiant that its scale – it is the biggest subscription streaming service, with 15 million paying customers and another 45 million free users – will ensure it does not miss out on new albums for long. “We want all the world’s music on our service, but there has been sporadic windowing on Spotify since it was ­created. We know from experience that these things happen, they come and go,” said Spotify’s head of communications and public policy, Jonathan Prince. “We continue to grow exponentially by delivering a great product for our users and the artists they love. Recent releases by Drake, Kendrick Lamar, Madonna and others show how critical it is for artists and labels to be on Spotify for their own success.” Spotify is currently under pressure from some major music labels, ­Universal Music Group in particular, to convert more of its free users into ­paying ­subscribers. Some artists – including ­Taylor Swift, who pulled her music from Spotify – have also criticised the free streaming model. Tidal will sidestep those arguments, since it does not have a free tier, a ­strategy also likely to be adopted by Apple. Swift’s back catalogue is already available on Tidal, as it is on all other paid-for streaming services. “This has never been changed. Big Machine Records [Swift’s label] believes music has value and we do not believe Taylor’s music should be made available for free,” a spokesman for Swift said. Not everyone is convinced that Tidal will revolutionise the music streaming market. “This isn’t about transforming the streaming market, or suddenly taking it into the mainstream. I think Tidal is aiming to compete around, rather than with, Spotify,” Mark Mulligan of music industry consultancy MIDiA Research told the Guardian. “It is aiming for a higher spending slice of the music ­aficionado market. Primarily this is about opening up new market segments, and the positioning is smart: it is creating an aspirational brand, which ties in well with the urban music community.” Exclusivity is key to that ­ambition. But, despite Jay Z’s impressive ­contacts book, labels will make the final ­decisions on such deals. For now, at least. One report ahead of Tidal’s relaunch suggested that Jay Z sees the company as a modern day music ­equivalent of United Artists, the ­Hollywood studio founded in 1919 by a group of actors and directors as a way to control their own output. Tidal’s long-term plan may be to sign big artists as their label deals run out, in which case it could become a rival not just to Apple and Spotify, but to major labels Universal, Sony and Warner. ||||| Jay Z doesn’t give many interviews. In conversation, he often pauses mid-sentence, considers, rewinds, slices and reshapes his answer, choosing a more appropriate word or analogy that draws a finer point before revealing it to the interviewer. What’s commonly assumed is a mistrust of the press may just be that unlike his work in the studio or onstage, Jay Z doesn’t ultimately control the final result of an interview, and therefore treads more carefully while giving one. Jay Z's Tidal Teaser Video Features Madonna, Beyonce, Jack White, & More And yet on the occasion of his recent $56 million purchase of Aspiro, a publicly traded Swedish tech company, and the blockbuster announcement that he is partnering in the venture, in both the spiritual and financial sense of the word, with music’s biggest names -- including giants from the world of hip-hop (Kanye West, Nicki Minaj), R&B; (Beyoncé, Rihanna), dance (Madonna, Calvin Harris, Daft Punk), rock (Jack White, Coldplay) and country (Jason Aldean) -- he sat with Billboard a few days before the March 30 announcement in an effort to explain his motives for a purchase that the industry has greeted with a raised eyebrow. Jay Z's Tidal Planning Flashy New York Event While it would be easy to dismiss the idea that a small company with 500,000 subscribers and a twice-the-price high-definition capability could ever compete on a cursory level with Goliaths like Spotify (60 million subscribers, 15 million of them paid) and the soon-to-relaunch Beats Music, one must consider the possibility that what he’s proposing isn’t a get-rich-quick scheme. According to Jay Z, and judging from the #TIDALforALL social media campaign that launched in March 30’s early morning hours, his primary goal is to change a broken compensation system and to bend the accepted limits of what’s offered for streaming, including song snippets, loose ideas and video. And by offering more money he will, in theory, force other streaming companies to follow suit. Much like his music that has occasionally served as a social agitator, Tidal, which is initially a playground for A-list performers, is Jay Z’s way of resetting music’s value proposition. None of the top-tier artists, who all reportedly own an equal share of the company, need the money, which make them the perfect delivery mechanism for his message: that musicians have had enough of streaming’s microscopic payouts and the labels’ helpless shrugs. Whether the industry itself has had enough remains to be seen. Billboard: When did it first occur to you to get into the streaming business? Jay Z: A year-and-a-half ago. We saw the movement and how everything was going and figured that this could possibly be the last music format that we see in this lifetime. We didn’t like the direction music was going and thought maybe we could get in and strike an honest blow and if, you know, the very least we did was make people wake up and try to improve the free vs. paid system, and promote fair trade, then it would be a win for us anyway. Musicians have long complained that streaming has rendered music virtually worthless. It doesn’t sound like you’re solely driven by financial reasons, but also by a desire to reset the value proposition of music. That’s correct, absolutely, and when I spoke to every single person involved that’s what I said. Music is … imagine your life without music. It’s a very valuable part of your life, and like I said, that’s why we got in this business. It seems to be going the other way. People are not respecting the music, and [are] devaluing it and devaluing what it really means. People really feel like music is free, but will pay $6 for water. You can drink water free out of the tap, and it’s good water. But they’re OK paying for it. It’s just the mind-set right now. In some ways music is probably closer to priceless than worthless. Yes. The experiences that I’ve had growing up with music, you know, I couldn’t trade them for any money in the world. Dancing in the living room to enjoy myself. “Enjoy Yourself,” Michael Jackson. Those moments and just that feeling of joy, it’s priceless, like you said. Someone of your stature can make this case to the other streaming services. Did you try that before you decided to buy in? Yeah, we talked to every single service and we explored all the options, including creating a white label with a service. But at the end of the day we figured if we’re going to shape this thing the way we see it then we need to have independence. And that became a better proposition for us -- not an easier one, mind you. The list of your partners is going to surprise quite a few people. How did you get them involved? Was it as simple as going out and saying, “This is our chance to turn the tide against this thing that’s happening”? Yeah, pretty much. I talked to everyone one on one about music and about what they would like to see in a service, and how would they like this to go. I wanted to know if they were willing to take a chance, since everyone’s names are attached and their reputations, too. And I just believe as long as we’re on the side of right, and we’re in this for the right reasons, it will work. It’s just a big opportunity for everyone -- not a thing that belongs to any one person. That’s not fair, that’s not a democratic process, and that isn’t the idea behind it. Isn’t another of your goals to make sure the revenue makes its way down the food chain to content creators? Definitely. For someone like me, I can go on tour. But what about the people working on the record, the content creators and not just the artists? If they’re not being compensated properly, then I think we’ll lose some writers and producers and people like that who depend on fair trade. Some would probably have to take another job, and I think we’ll lose some great writers in the process. Is it fair? No. If you put in work, everyone else, you go to work you get paid. That’s fair trade. It’s what our country is built on. I’m just saying the producers and people who work on music are getting left out -- that’s when it starts getting criminal. It’s like you’re working hard and you’re not receiving. In any other business people would be standing before Congress. They have antitrust laws against this kind of behavior. It almost seems like when it applies to music no one really cares who’s cheated. It’s so disorganized; it’s so disconnected from reality. What made Aspiro the company to help you make this statement? Was it anything to do with the fact that it’s a smaller, foreign company that you could buy more quietly? That had a bit to do with it. We had to move pretty quietly because we wanted to do it right without interference. But … the service [also] offers high-quality audio and video. Again, we’re talking about respecting the music and respecting the art … and we can’t play around with that, so we need something that’s authentic and honest. That made it pretty attractive pretty quickly, that the sound quality was so high, and I would know, because I’ve personally heard 70 mixes of a single record, you know what I'm saying? So the least I can do is try to present that to the public the way that the artist intended. Are you going after the high-end audiophile or just people who care enough about music to pay almost twice as much for the service? We want it to be open to everyone. So yeah, that would be part of it, but the pricing will be tiered, because we want to present it to as many people as possible. But it definitely appeals to people who really care about the music and want to hear it the way it’s intended. And hopefully some day with technology we figure out how to deliver that high-def sound, maybe even in a $9.99 model. Who knows what the future holds. Do you think video is going to play a big part in separating you from the other streaming services? That’s certainly a differentiator, and we’ll have high-quality videos and hopefully we’ll see something that we haven’t seen before. Have you been talking to phone carriers and audio partners? We’ve heard AT&T; and Skullcandy... We’ve been speaking to a lot of people. To single someone out wouldn’t be fair for them or us. So, Tidal launches today. Creatively, what do you hope happens, beginning tomorrow? Artists come here and start making songs 18 minutes long, or whatever. I know this is going to sound crazy, but maybe they start attempting to make a “Like a Rolling Stone,” you know, a song that doesn’t have a recognizable hook, but is still considered one of the greatest songs of all time, the freedom that this platform will allow art to flourish here. And we’re encouraging people to put it in any format they like. It doesn't have to be three minutes and 30 seconds. What if it’s a minute and 17, what if it’s 11; you know, just break format. What if it’s just four minutes of just music and then you start rapping? It sounds more like you’re envisioning it as a creative collective, or a salon, where artists can try things out and let the audience decide if that’s a direction they should continue in. That’s right. That’s a pretty persuasive sort of pitch to make to an artist. Did the first tier immediately get it, or was there some resistance? I think there was a bit of nervousness because of how things work: This is something new and unknown. But at the core everyone was super-excited at the idea. Like “Yes, let’s do this. Let’s not only create a place that has great music — let’s protect the future generation of artists.” I think this thing changes the world for them. It makes everything different, you know? Between those things it was like, “We have to do this, we are almost charged in this position to do it.” So, you’re an owner and a musician. Are you hoping that the other services will begin to adopt this attitude, or are you content because if they don’t adopt this you’ll have your own point of differentiation? I think the goals are the same. Like when the tide rises, all the boats rise. That’s the first thing I said to the group was, “If for nothing else, then we just caused people to look inside their organization and say, ‘Yeah, let’s work on this, let’s work on audio, and let’s work on a pay system.’ ” I already see the conversations, I already see how it’s changing -- and it may have changed anyway because that’s just the natural process when things are wrong -- but I think we sped it up already, and we’re not even out yet. I already see the discussions and the scrambling. And we haven’t even begun. Each first-tier person has equity in the company? Yes. Is it the same equity across the board? Yes. We’re super-transparent, and I think that’s part of it. We want to be transparent, we want to give people their data; they can see it. If somebody streams your record in Iowa, you see it. No more shell games. Just transparency. So the founding members all got the same equity, and now we have a second round and everyone gets the same in that one as well, but it’s not as large as the first tier. We want to keep it going. We want to make this thing successful and then create another round and another round. That’s the dream, that’s the utopia. Everyone is sharing in it; everyone is some kind of owner in it in some kind of way. What’s been the response from the labels? I think the labels were a bit suspicious that we were creating a record company. It’s not a record company; if anything, it’s a record store. I have a record company. I don’t want another label. I’m happy with what I’m doing. But some were suspicious. We had talks, like, “Man, you guys also ought to bless this talent. We want you to be involved in this thing as well.” Again, we’re not even against other streaming companies. We want everyone to do well. We just want to carve out our section and let our voice be heard. So yeah, I think there is a bit of paranoia in the beginning and there may still be, and I think we’ll work through that because it will be a very difficult thing for a label to tell artists when they’re streaming their music everywhere else that they won’t stream it on an artist-owned platform. I don’t see how any label can stand in front of anyone and justify that. The stature of artists you have aligned with virtually assures that freedom. Are the artists going to provide exclusive tracks or release windows on future work? Well, it’s up to the artist. You know, there’s a thing now, it’s called the album cycle. You put your single out, promote it, then another single -- I think that now for an artist an album cycle doesn’t have to end. They’re on Instagram and Twitter and all these things, so we’re just talking about ways of extending that album cycle, and it could be anything. What if it’s a video offering tickets to the next concert, or what if it’s audio or video of the recording process? It could be anything. It could be them at home listening to songs that inspire them. Anything they want to offer, you know; just be as creative as possible, that’s the only charge, really. Make it look really good and make everyone that consumes it think, “Man, I got something really great.” Treat the people with respect; make it memorable. The music industry is obviously cynical. When you came out with your vision, musicians aside, what was the response from the business community? I think they were receptive but thought that there was no way I could pull it off. You know: “That’s what’s supposed to happen, but no way you’re going to do that.” Still, today I can’t imagine that [Creative Artists Agency] is not having a meeting with their artists [and saying], “Let’s figure out how to do something together.” But I think it’s so hard to get done. I think it’s so hard because of ego. I think it just was a moment in time and we felt like, “Yes, this is the thing that if it works we’ll be successful, but if it worked, then the music business will also be successful.” And I think that was so appealing. But the answer was yes, people are like, “That’s what should happen, but you’ll never get it done.” Is that part of what’s driving you? When was the last time you were the underdog in a fight? I don’t know; I feel like that all the time. I feel like I’m always pushing envelopes. I feel like I couldn’t get a record deal; I feel like, you know, when Hot 97 [New York] was the big station, I was the first one on Power 105 [New York]. When The Source was the biggest magazine, I was first one on the cover of XXL. Twelve months from now, what would be your definition of success with Tidal? It doesn’t sound like it’s a financial benchmark. If everyone says, “Wow, so many things have changed. This has gotten better. I like what's happening.” If Aloe Blacc and his writers, the guys he wrote with, are not seeing a $4,000 check from 168 million streams. They did their job, they worked, they done it. The people loved it, the people consumed it. Where’d it go? People didn’t pay or stream Aloe Blacc’s music for it to turn into vapor and go into the air. Where is it? If in 12 months everyone is having that discussion and a dialogue, and everyone is understanding that streaming’s not a bad thing, I’m happy. Let’s embrace what’s coming up next. When the biggest distributor of downloads says they’re going to start a streaming company, I mean, I don’t know what more you need to know that it’s the next format. You have a long-standing relationship with Jimmy Iovine. Have you been in contact with him since the news has started trickling out? Yeah, of course. My thing with Jimmy is, “Listen, Jimmy; you’re Jimmy Iovine, and you’re Apple, and truthfully, you're great. You guys are going to do great things with Beats, but … you know, I don’t have to lose in order for you guys to win, and let’s just remember that.” Again, I’m not angry. I actually told him, “Yo, you should be helping me. This is for the artist. These are people that you supported your whole life. You know, this is good.” Have you heard the rumor that he’s trying to lure people from your first-tier group by offering them more money upfront? I think that’s just his competitive nature, and I don’t know if he’s looking at the bigger picture: That it’s not about me and it’s not about him; it’s about the future of the music business. When you were starting your career, if streaming was the pre-eminent revenue vehicle for recorded music, would you have still pursued music? Maybe. But I think that the people that work behind the scenes maybe wouldn’t have. Can you say definitively that they are going to make more money from Tidal than Spotify? It’s not me against Spotify, but for us, you know, just the idea of the way we came into it, with everyone having equity, will open the dialogue — whether it be with the labels, the publishers or whoever, I think it’s those sorts of conversations that need to be had, and again, not by forcing anyone to do it. We're not forcing anyone to do anything, we're just introducing ideas, and I don't know, maybe someone else comes up with the idea. Maybe someone from the label comes up with the idea, maybe a lawyer; someone finds a bunch of different things that we think will work. Will artists make more money? Even if it means less profit for our bottom line, absolutely. That’s easy for us. We can do that. Less profit for our bottom line, more money for the artist; fantastic. Let’s do that today. ||||| Media playback is unsupported on your device Media caption Peter Bowes reports: "Some of the biggest names in the industry have a stake in the company" Some of the biggest names in entertainment have re-launched the music subscription service Tidal, which they are billing as the first artist-owned platform for music and video. At an event in New York on Monday, Madonna, Beyonce, Kanye West, and 13 other performers announced they had become co-owners of Tidal. The service launched last October, but was recently bought by rapper Jay Z. It is hoping to compete with the likes of Spotify, Deezer and Google Play. However Tidal offers 25 million music tracks, fewer than the 30 million offered by many rival services. As well as a standard subscription for $9.99 a month, Tidal offers a "high fidelity" option for $19.99, which claims to deliver better sound quality. Image copyright AFP Image caption Alicia Keys said they would make history Singer Alicia Keys spoke on behalf of the artists as they all lined up on stage at Skylight at Moynihan Station in Manhattan. Describing the event as a "graduation", she said the artists hoped Tidal would alter musical evolution. "So we come together before you on this day, March 30th, 2015, with one voice in unity in the hopes that today will be another one of those moments in time, a moment that will forever change the course of music history." Their mission, she said, goes beyond commerce and technology. "Our intent is to preserve music's importance in our lives,'' she said. Notably, the majority of the company will be owned by artists, a symbolic move in a business where musicians often have little control over how their work is distributed and consumed. Jay Z's strategy will include encouraging artists to lobby their labels to give Tidal new music a week in advance of other services, giving it a short window of exclusivity. He told Billboard: "We didn't like the direction music was going and thought maybe we could get in and strike an honest blow. "Will artists make more money? Even if it means less profit for our bottom line, absolutely. That's easy for us. We can do that. Less profit for our bottom line, more money for the artist; fantastic."

– Jay Z relaunched the Tidal music streaming service last night at a New York City event with more than a dozen other co-owners, including Beyonce, Daft Punk, Madonna, Rihanna, Jack White, and Alicia Keys, who said the assembled artists hoped the launch would be a "moment that will forever change the course of music history," the BBC reports. More on the service, which inspired artists to turn their social media profiles blue: The big difference with Tidal, Jay Z says, is that it's owned by artists and will treat artists with respect. "The challenge is to get everyone to respect music again, to recognize its value," he tells the New York Times. "Water is free. Music is $6, but no one wants to pay for music. You should drink free water from the tap—it's a beautiful thing. And if you want to hear the most beautiful song, then support the artist." The Times reports that he recently paid $56 million for the service. Tidal, which currently has around 35,000 subscribers paying $19.99 a month for a "high fidelity" service that promises better sound quality, also has a standard $9.99 option, reports TechCrunch, which says sources are claiming the service is paying artists twice as much as rivals like Spotify. Including the standard service, Tidal had around 500,000 subscribers by the end of last year, according to the Guardian, which notes that unlike Spotify, it offers no free tier. Jay Z says part of the aim is to make sure people lower down the food chain than artists get a fair deal. The "producers and people who work on music are getting left out—that's when it starts getting criminal. It's like you're working hard and you're not receiving," he tells Billboard. "In any other business, people would be standing before Congress. They have antitrust laws against this kind of behavior. It almost seems like when it applies to music, no one really cares who's cheated." Tidal may not be able to overtake Spotify, which counts 15 million paying customers among its 60 million users, but analysts say that might not be its goal. "It is aiming for a higher spending slice of the music ­aficionado market," an industry consultant tells the Guardian. "Primarily this is about opening up new market segments, and the positioning is smart: It is creating an aspirational brand, which ties in well with the urban music community." Skeptics include Sam Biddle at Gawker, who was not impressed by the "bonkers" relaunch event. The artists involved "think you are willing to pay up to double the price of other streaming music services to pay for their streaming music service, because they are crazy," he writes.

the ads / cft correspondence introduced by maldacena @xcite has helped shed light on behaviors of systems otherwise far too complicated to tackle . specifically , it has given us a method by which strongly interacting regimes of theories can be studied quite easily through considering the dual gravity theory which is mostly described by geometry . also , it allows us to study responses to the field theory to background electromagnetic fields by introducing gauge fields in the bulk , which is another simplifying feature . many ads / cft systems with a background magnetic field have been studied , especially in the case of the ads@xmath7 magnetic brane used to investigate 2 + 1 gauge theories in magnetic fields @xcite . also , ads@xmath5 case has been tackled in @xcite , which was motivated by rhic physics which involves strongly coupled gauge theories in magnetic fields @xcite . a slight generalization of the configuration of the magnetic fields can prove to be useful in shedding light on more exotic features of the system . another interesting aspect of ads / cft is the correspondence in 2 dimensions , i.e. ads@xmath8/cft@xmath9 . as opposed to common belief that smaller dimension means simpler physics , this case of the duality has proven to be the least understood @xcite . this is partly due to the disconnected feature of the boundary of the ads@xmath1 space , giving us two disconnected dual descriptions commonly understood to be systems described by conformal quantum mechanics . recent interest stems from the emergence of quantum critical behavior in this duality . such behavior , involving non - fermi liquid behavior , was studied in @xcite . a new setup showing the the emergence of the ads@xmath1 space - time will prove useful to the cause of understanding the duality in 2 dimensions . driven by these motivations we consider bulk solutions that interpolate between ads@xmath5 in the uv regime and ads@xmath0@xmath10t@xmath11 in the ir along with the presence of a magnetic field . a similar system was studied in @xcite but we generalize the problem by considering a magnetic field that is comprised of a linear combination of three @xmath3 s of @xmath4 . in this generalization , the linear combination is parameterized by elements of the unimodular tensor , @xmath12 , that is in the 20 representation of @xmath4 which emerges from the deformations of the 5-sphere in the ads@xmath5@xmath13 after truncation @xcite . we consider a simple diagonal form for the tensor with three parameters @xmath14 . at finite temperature , the large coupling limit is the product of a btz black hole and a t@xmath11 . the entropy is found to scale as @xmath15 , temperature , just as in @xcite . the added feature in our result is that the entropy is also a function of the linear combination parameters , @xmath16 . we also consider the effect of this generalization on the @xmath17 sym theory . the charged particles are now charged under a linear combination of the @xmath18 magnetic fields . it s entropy too depends on the linear combination parameters . the relation between the entropies takes the form @xmath19 where the peak of the function @xmath20 , occurring at @xmath21 , corresponds to the result @xmath22 obtained in @xcite . we also find solutions for arbitrary @xmath23 below the peak value . this is an indication of the influence of the chosen linear combination on the physics of the problem . next , we look at the other system of interest which interpolates between ads@xmath5 and ads@xmath1@xmath10t@xmath24 . the magnetic field considered has the added feature that each @xmath3 points in a different direction in physical space ; one along each direction of the torus . we find that this system can be solved exactly , and we obtain the interpolating solution for all @xmath25 . we find that the solution interpolates between ads@xmath5 at large @xmath25 and the product of an extremal two dimensional black hole with t@xmath24 . the black hole thus has finite entropy at zero temperature hinting at a 1 dimensional dual field theory with a degenerate ground state . across the duality , we show that ads@xmath1 magnetic field configuration does not alter the temperature scaling of the entropy . we then show that we still have the regular free @xmath17 sym theory , with zero entropy at zero temperature . finally , we investigate the stability properties of the solutions at hand , as this is often a problem for condensed matter applications of ads / cft duality . we consider small perturbations of the unimodular tensor away from the identity . we find two classes of solutions having different @xmath26 . we find that for both space - times the @xmath26 s are well above the respective @xmath27 . thus both the space - times are stable . in this paper , we start in section 2 by constructing the space - time that interpolates between ads@xmath5 and ads@xmath28t@xmath11 and we compute the relevant entropy . in section 3 we discuss the @xmath17 sym dual field theory and compare the entropies . then we go on to investigate the thermodynamics of the ads@xmath5/ads@xmath29t@xmath11 space - time in section 4 . in section 5 we present an argument showing that the entropy of the free field limit of @xmath17 sym still scales as temperature for the ads@xmath1 magnetic field configuration . in section 6 we discuss the stability of the space - times considered by computing the @xmath26 of the unimodular tensor fields . we use the results obtained by @xcite in truncating the 10 dimensional iib theory to a 5 dimensional einstein - maxwell theory . the kaluza - klein reduction ansatz is given by @xmath30 where @xmath31 where @xmath12 is a symmetric 6@xmath106 unimodular tensor used to represent the 20 scalars in the 20 representation of @xmath4 . this also represents the l @xmath32 deformation of the 5-sphere . the @xmath33 are the 1-form potentials , antisymmetric in @xmath34 and @xmath35 , that represent the 15 @xmath4 yang - mills gauge fields . the radius of the five compact dimensions is given by the inverse of @xmath36 . also just to define some notation , here are a few important relations @xmath37 where @xmath38 is the usual covariant derivative . the first two equations are in form notation while the third is in terms of tensors . + the truncated lagrangian has the form @xmath39 where @xmath40 is a potential given by @xmath41 also we have omitted chern - simons terms that will not contribute to the physical system of interest to us . the unimodular tensor field equation that one obtains from this lagrangian is @xmath42 \label{tmotion}\end{aligned}\ ] ] the solutions we are looking for are those that interpolate between ads@xmath5 at high energies and ads@xmath0@xmath10t@xmath11 and low energies . we are also interested in incorporating a magnetic field that is tangent to the boundary directions . we also assume lorentz invariance in the boundary spatial directions orthogonal to the magnetic field . the metric ansatz then takes the form @xmath43 we are interested in a magnetic field that is a linear combination of three different @xmath3 s taken out from the group @xmath4 . we can obtain this via the following choice of @xmath12 and the maxwell stress tensor @xmath44 @xmath45 where @xmath46 and the unimodular condition becomes @xmath47 . with our choice of @xmath12 and maxwell tensor @xmath44 , we go ahead to solve the tensor field equations ( [ tmotion ] ) . we do this with the assumption that @xmath12 is a constant in the near horizon regime . due to complexity of solving for the @xmath48 we instead solve for @xmath49 to get the relations @xmath50 plus the cyclic permutations in 1 , 2 , and 3 . next , the langrangian for the truncated theory becomes @xmath51 where the @xmath52 is now @xmath53 implementing our ansatz for the metric , we obtain the following einstein s equations @xmath54 where @xmath55 we now look for the required solutions . for @xmath56 , we have the solution representing ads@xmath5 given by the usual metric @xmath57 this is the expected uv solution , located at @xmath58 , of our theory . in this region the magnetic field becomes negligible and can be ignored . the next case is with @xmath59 ; this will represent the field theory at longer length scales , and thus is expected to be located at finite @xmath25 . the field equations produce the following solution at the ir @xmath60 this ir solution represents the product between a btz black hole and a torus , t@xmath11 . we see that at zero temperature we obtain ads@xmath61@xmath10t@xmath11 . the entropy of the btz black hole is given by @xmath62 , where @xmath15 is temperature , @xmath63 is the length of the @xmath64 direction , and @xmath65 is the central charge . we obtain the central charge using the brown - henneaux formula @xcite , @xmath66 , where @xmath67 is the ads@xmath0 radius given by @xmath68 , and @xmath69 is the 3 dimensional gravitational constant . we can write @xmath69 as @xmath70 , where @xmath71 is the volume of the two compact dimensions @xmath72 . simplifying the expression further , we write @xmath73 in terms of relevant string theory constants to get @xmath74 where @xmath75 unit volume of the @xmath76 dimensions @xmath77 , and @xmath78 comes from defining the integral of the 5-form as @xmath79 , and @xmath80 is the number of branes , which is given by @xmath81 we note that @xmath82 is a function of the charges , and thus a function of the elements of the unimodular tensor , @xmath12 . now that we have the central charge on the gravity side , we proceed to obtain the central charge across the duality and compare . we go on now to calculate the entropy of the free field limit of @xmath17 sym theory in an external magnetic field . we consider the @xmath17 theory in @xmath84 terms , with a @xmath3 r - symmetry . in this theory , we have @xmath85 complex scalars of each charge , @xmath86 , @xmath87 , and @xmath88 . these are the scalars in the chiral multiplet . we also have @xmath85 vector fields of charge 0 , these are the gauge fields . from the charges of the complex scalars we obtain the charges of the fermions of the chiral multiplet and the gauginos to be @xmath89 so we have @xmath85 weyl spinors of each charge @xmath90 , @xmath91 , and @xmath92 . these are the fermions of the chiral multiplet . and finally we have @xmath85 weyl spinors of charge @xmath93 , these are the gauginos . + next we write down the logarithm of the partition function for each type of field . for the details of obtaining these we refer the reader to @xcite . the expressions are @xmath94 @xmath10t@xmath11 theory and the @xmath17 sym free field theory . on the right we have the ratio as a function of @xmath95 . on the left we have a slice through @xmath96 . [ cc],width=264 ] @xmath10t@xmath11 theory and the @xmath17 sym free field theory . on the right we have the ratio as a function of @xmath95 . on the left we have a slice through @xmath96 . [ cc],width=264 ] we are interested in calculating the entropy in the extremely low temperature limit . we use the standard formula , @xmath97 . in the required limit , the only contribution we have is the fermionic term with @xmath98 which gives @xmath99 we compare the central charges of the two theories across the duality . we consider the ratio @xmath100 . simplifying this , we find it to be a function of any two of the set ( @xmath101 , @xmath102 , @xmath103 ) . figure ( [ cc ] ) shows a plot of @xmath100 as a function of @xmath101 and @xmath102 , along with a slice through the @xmath96 plane . the result of @xcite is reproduced at the point @xmath104 , which corresponds to the peak of @xmath100 where @xmath105 . we also note the wide range of values of @xmath100 as we vary the linear combination of our gauge fields in group space . in this section we search for a different type of solution motivated by finding a field theory dual that lives in one dimension . we thus look for a solution to the truncated iib theory that interpolates between ads@xmath5 at large @xmath25 and ads@xmath106t@xmath24 at small @xmath25 . the ansatz we choose has both translational and rotational symmetry in the toroidal directions . this is manifest in the following metric @xmath107 the magnetic field we consider in this section is a linear combination of fields that point in different directions in actual space ; one along each toroidal direction . also , each magnetic field will be chosen to be part of a different @xmath3 as before . while the unimodular tensor , @xmath12 , remains the same , the maxwell tensor will then be chosen as @xmath108 where we set the magnetic fields to point in orthogonal directions , as shown below @xmath109 upon solving the tensor field equations for @xmath49 we find @xmath110 plus the cyclic permutation in 1 , 2 , and 3 . the lagrangian is slightly modified from the previous case @xmath111 where @xmath52 is given in eq . ( [ potential ] ) . varying the action we obtain the following einstein s field equations @xmath112 with @xmath113 these field equations , along with the scalar field equation result for @xmath114 , [ ads2tmotion ] , constrain our choice of the magnitudes of the magnetic fields , charges , and the @xmath12 entries . we are forced to set @xmath115 the field equations then take a simpler form and can be solved exactly . at the uv limit we impose @xmath56 . the result , as expected , is the usual ads@xmath5 solution given by @xmath116 next , we turn on the magnetic field and solve the field equations exactly for @xmath117 and @xmath118 . we note that there are two types of solutions to the einstein s field equation ; one where @xmath119 is taken to be a constant , and the other is where @xmath118 varies with @xmath25 . we expect that the constant @xmath120 solution be a limiting case of the varying solution . we choose to place the constant value at @xmath121 which will be the location of the horizon of the black hole . solving for @xmath117 we find that it does indeed have a solution that vanishes at an @xmath121 giving us a horizon . we also find that when we place the @xmath120 at @xmath121 the solution of the black hole becomes an extremal one . it s metric is given by @xmath122 which is the product between a two - dimensional black hole and a three torus , t@xmath24 as required . calculating the temperature of this black hole we find it to be @xmath123 as expected of a black hole at extremality . the interesting aspect of this black hole is that we can still go ahead and calculate an entropy at zero temperature . we do so by using the standard formula , @xmath124 , with the area , @xmath125 , being @xmath126 as for the gravitational constant , we have the usual ads / cft relation , @xmath127 . we note that the relations used here are much simpler than those used in in section 2 because of the simpler form of @xmath128 . this means that the @xmath129 is not deformed which simplifies many of the equations in the truncation process . finally we compute the entropy to be @xmath130 we emphasize again that this entropy is finite at zero temperature . this implies that our gravity theory is dual to a field theory with a degenerate ground state at large coupling . we proceed now to evaluate the entropy of the free field limit of the dual theory . the particle content here is identical to the one in section 3 . the difference comes in the value of the assigned charges . the complex scalars each are assigned the charge @xmath131 . three of the weyl fermions are assigned the charge @xmath132 and the gaugino is assigned the charge @xmath133 . the claim now is that not much has changed from the previous case in section 3 . since the scalars transform under the @xmath134 of @xmath4 each complex scalar component will be charged under only one gauge field , thus its energy eigenstates will not change and the partition function will not be altered . since the gauge field is not charged , we expect that it also will attain the same partition function . as for the weyl fermions , they transform as a @xmath135 of @xmath4 . thus each component will be charged under a linear combination of the different @xmath3 s and hence of the different magnetic fields pointing in the different directions . however , we will show with an example that this does not alter the answer except by a change in the magnitude of the magnetic field it feels . here is a simple heuristic argument : since the fermions are charged equally under all three fields , then it will feel a resultant field equal to the square root of the sum of each magnetic field squared , @xmath136 . as for the direction of @xmath137 , this depends on the details of @xmath3 linear combination for each fermion . + here is the example : consider a fermion , @xmath138 , charged under the three @xmath3 s in the following way @xmath139 where @xmath140 the covariant derivative then becomes @xmath141 under a simple change of basis , we can write this in a much more transparent form @xmath142 thus in this basis , the fermion , @xmath143 , is charged under the gauge field @xmath144 . the conclusion is then that the entropy for this system will have the same behavior as was found previously ; it will vanish as @xmath145 . explicitly , the entropy will be @xmath146 we remind ourselves with the result of the previous section where we found the entropy to be finite at zero temperature . thus we have found a conflict in the behaviors of the systems across the duality . the weakly coupled picture suggests a new mechanism for local quantum criticality ( a. almuhairi and j. polchinski , work in progress ) . a charge in a magnetic field can only move parallel to field lines . for a composite operator whose constituents move in different directions , the correlator will be local in position space , and exhibit critical behavior only in time . in this section we investigate the stability properties of the two space - times ads@xmath28t@xmath11 and ads@xmath29t@xmath24 with respect to perturbations of the unimodular tensor field . we consider the perturbation as @xmath147 , where @xmath148 = 0 $ ] because @xmath149 = 1 $ ] . as usual , we are looking for the field equations of the perturbations from which we can extract the @xmath26 ; we use the @xmath12 field equations given in above in eq . [ tmotion ] . also across the duality , we expect @xmath12 to correspond to a dimension 2 operator , and thus its @xmath150 in the case of no magnetic field . this is already saturating the bf - bound . thus we hope that the magnetic field stabilizes this and does not tip the mass in the wrong direction . the linearized matrix equation of motion is @xmath151_{i j } + g^2 [ a_\mu , [ a^\mu , t]]_{i j } = -4g^2 t_{i j } - \frac{1}{2}(t f^2)_{i j } - \frac{1}{2}(f_{\mu \nu}tf^{\mu \nu})_{i j}\ ] ] these set of equations become diagonal when we construct the linear combination of @xmath152 s : @xmath153 and @xmath154 , where @xmath155 . due to the traceless property of @xmath152 , the solutions for @xmath156 mix together and we are forced to pick the combinations @xmath157 , along with the other two cyclic terms . carrying out the algebra one finds the following @xmath26 . for ads@xmath0 @xmath158 for ads@xmath1 @xmath159 , \ for\ all \ i\\ & m^2_{z_1 \bar{z_1 } + z_2 \bar{z_2 } - 2 z_3 \bar{z_3 } } = 12 g^2 , \ also \ for \ cyclic \ in \ ( 1,2,3)\end{aligned}\ ] ] where @xmath160 designates the landau level excitation . we find that all the @xmath26 s are positive and thus safely above the @xmath161 for both space - times . hence the magnetic field acts as a stabilizing mechanism in this problem . in this paper we have generalized solutions pertaining to magnetic branes in ads . we have shown that a more general configuration of magnetic fields gives us control over tuning the ratio between the entropies across the duality in the ads@xmath0 case . there are solutions that can fix the entropies to be identical . this manipulation shows how dependent the physics at large coupling is on the configuration of the magnetic field . + we also investigated the ads@xmath1 case , where we found that the black hole solution was an extremal one . this gave us a finite entropy at zero temperature . upon comparing this with the field theory , we observe a conflict , since the field theory entropy scales with temperature . this indicates the presence of a phase transition when turning up the coupling . this is a problem worth tackling . + finally , we studied the stability properties of both space - times and showed that they are stable . in fact we find that the usual dimension two tachyon operator gets a boost in its @xmath26 due to the presence of the magnetic field . thus the magnetic field acts as a stabilizing agent . j. m. maldacena , `` the large n limit of superconformal field theories and supergravity , '' adv . * 2 * , 231 ( 1998 ) [ int . j. theor . phys . * 38 * , 1113 ( 1999 ) ] [ arxiv : hep - th/9711200 ] . s. a. hartnoll and p. kovtun , `` hall conductivity from dyonic black holes , '' phys . d * 76 * , 066001 ( 2007 ) [ arxiv:0704.1160 [ hep - th ] ] . s. a. hartnoll , p. k. kovtun , m. muller and s. sachdev , `` theory of the nernst effect near quantum phase transitions in condensed matter , and in dyonic black holes , '' phys . b * 76 * , 144502 ( 2007 ) [ arxiv:0706.3215 [ cond-mat.str-el ] ] . e. dhoker and p. kraus , `` magnetic brane solutions in ads , '' jhep * 0910 * , 088 ( 2009 ) [ arxiv:0908.3875 [ hep - th ] ] . d. t. son and p. surowka , `` hydrodynamics with triangle anomalies , '' phys . rev . lett . * 103 * , 191601 ( 2009 ) [ arxiv:0906.5044 [ hep - th ] ] . a. strominger , jhep * 9901 * , 007 ( 1999 ) [ arxiv : hep - th/9809027 ] . t. faulkner , h. liu , j. mcgreevy and d. vegh , `` emergent quantum criticality , fermi surfaces , and ads2 , '' arxiv:0907.2694 [ hep - th ] . t. faulkner and j. polchinski , `` semi - holographic fermi liquids , '' arxiv:1001.5049 [ hep - th ] . m. cvetic , h. lu , c. n. pope , a. sadrzadeh and t. a. tran , `` consistent so(6 ) reduction of type iib supergravity on s(5 ) , '' nucl . phys . b * 586 * , 275 ( 2000 ) [ arxiv : hep - th/0003103 ] . j. d. brown and m. henneaux , `` central charges in the canonical realization of asymptotic symmetries : an example from three - dimensional gravity , '' commun . phys . * 104 * , 207 ( 1986 ) .

we investigate ads@xmath0 and ads@xmath1 magnetic brane solutions within the consistent truncation of ads@xmath2 supergravity . the ads@xmath0 solution extends earlier work by allowing a general embedding of the magnetic @xmath3 in @xmath4 . we determine the ratio of strong- and weak - coupling entropies as a function of this embedding . further , by considering crossed magnetic fields in different @xmath3 s we are able to construct a solution that runs from ads@xmath5 in the uv to ads@xmath6 in the ir . we find the notable result that there is a zero temperature entropy at strong coupling but not at weak coupling . we also show that the ads@xmath1 solution and at least some of the ads@xmath0 solutions are stable within the truncation . * * * ads@xmath0 and ads@xmath1 magnetic brane solutions * * ahmed almuhairi * _ department of physics , university of california , + santa barbara , california 93106 , usa _

SECTION 1. SHORT TITLE. This Act may be cited as the ``Gulf Coast Restoration Act''. SEC. 2. GULF COAST ECOSYSTEM RESTORATION. (a) Definitions.--In this section: (1) Chair.--The term ``Chair'' means the Chair of the Task Force appointed under subsection (d)(3). (2) State coastal ecosystem restoration plan.--The term ``State Coastal Ecosystem Restoration Plan'' means a plan submitted under subsection (c) by a qualifying State to the Task Force. (3) Fund.--The term ``Fund'' means the Gulf Coast Ecosystem Restoration Fund established by subsection (b)(2)(A). (4) Governors.--The term ``Governors'' means the Governors of each of the States of Alabama, Florida, Louisiana, Mississippi, and Texas. (5) Gulf coast ecosystem.--The term ``Gulf Coast ecosystem'' means the coastal zones, as determined pursuant to the Coastal Zone Management Act of 1972 (16 U.S.C. 1451 et seq.), of the States of Alabama, Florida, Louisiana, Mississippi, and Texas and adjacent State waters and areas of the outer Continental Shelf, adversely impacted by the blowout and explosion of the mobile offshore drilling unit Deepwater Horizon that occurred on April 20, 2010, and resulting hydrocarbon releases into the environment. (6) Secretary.--The term ``Secretary'' means the Secretary of the Interior. (7) Qualifying state.--The term ``qualifying State'' means each of the States of Alabama, Florida, Louisiana, Mississippi, and Texas. (8) Task force.--The term ``Task Force'' means the Gulf Coast Ecosystem Restoration Task Force established by subsection (d). (b) Gulf Coast Ecosystem Restoration.-- (1) In general.--In accordance with this section, the Chair shall review and approve or disapprove State Coastal Ecosystem Restoration Plans submitted by the Governors that provide for restoration activities with respect to the Gulf Coast ecosystem. (2) Gulf coast ecosystem restoration fund.-- (A) Establishment.--There is established in the Treasury of the United States a fund to be known as the ``Gulf Coast Ecosystem Restoration Fund''. (B) Transfers to fund.--Notwithstanding any other provision of law, the Secretary of the Treasury shall deposit into the Fund amounts equal to not less than 80 percent of any amounts collected by the United States as penalties, settlements, or fines under sections 309 and 311 of the Federal Water Pollution Control Act (33 U.S.C. 1319, 1321) in relation to the blowout and explosion of the mobile offshore drilling unit Deepwater Horizon that occurred on April 20, 2010, and resulting hydrocarbon releases into the environment. (C) Authorized uses.--The Fund shall be available to the Chair for the conservation, protection, and restoration of the Gulf Coast ecosystem in accordance with State Coastal Ecosystem Restoration Plans submitted by the Governors and approved by the Chair under this section. (3) Disbursement.--The Chair shall disburse to each qualifying State for which the Chair has approved a State Coastal Ecosystem Restoration Plan under this section such funds as are allocated to the qualifying State under this section. (4) Use of funds by qualifying state.--A qualifying State shall use all amounts received under this section, including any amount deposited in a trust fund that is administered by the State and dedicated to uses consistent with this section, in accordance with all applicable Federal and State law, only for 1 or more of the following purposes: (A) Projects and activities for the conservation, protection, or restoration of coastal areas, including wetlands. (B) Mitigation of damage to fish, wildlife, or natural resources. (C) Planning assistance and the administrative costs of complying with this section. (D) Implementation of a federally approved marine, coastal, or comprehensive conservation management plan. (c) State Coastal Ecosystem Restoration Plan.-- (1) Submission of state plans.-- (A) In general.--Not later than October 1, 2011, the Governor of a qualifying State shall submit to the Chair a State Coastal Ecosystem Restoration Plan. (B) Public participation.--In carrying out subparagraph (A), the Governor shall solicit local input and provide for public participation in the development of the plan. (2) Approval.-- (A) In general.--The Chair must approve a plan of a qualifying State submitted under paragraph (1) before disbursing any amount to the qualifying State under this section. (B) Required components.--The Chair shall approve a plan submitted by a qualifying State under paragraph (1) if-- (i) the Chair determines that the plan is consistent with the uses described in subsection (b); and (ii) the plan contains-- (I) the name of the State agency that will have the authority to represent and act on behalf of the State in dealing with the Secretary for purposes of this section; (II) a program for the implementation of the plan that describes how the amounts provided under this section to the qualifying State will be used; and (III) a certification by the Governor that ample opportunity has been provided for public participation in the development and revision of the plan. (3) Amendments.--Any amendment to a plan submitted under paragraph (1) shall be-- (A) developed in accordance with this subsection; and (B) submitted to the Chair for approval or disapproval under paragraph (4). (4) Procedure.--Not later than 60 days after the date on which a plan or amendment to a plan is submitted under paragraph (1) or (3), respectively, the Chair shall approve or disapprove the plan or amendment. (d) Gulf Coast Ecosystem Restoration Task Force.-- (1) Establishment.--There is established the Gulf Coast Ecosystem Restoration Task Force. (2) Membership.--The Task Force shall consist of the following members, or in the case of a Federal agency, a designee at the level of Assistant Secretary or the equivalent: (A) The Secretary. (B) The Secretary of Commerce. (C) The Secretary of the Army. (D) The Attorney General. (E) The Secretary of Homeland Security. (F) The Administrator of the Environmental Protection Agency. (G) The Commandant of the Coast Guard. (H) The Secretary of Transportation. (I) The Secretary of Agriculture. (J) A representative of each affected Indian tribe, appointed by the Secretary based on the recommendations of the tribal chairman. (K) Two representatives of each of the States of Alabama, Florida, Louisiana, Mississippi, and Texas, appointed by the Governor of each State, respectively. (L) Two representatives of local government within each of the States of Alabama, Florida, Louisiana, Mississippi, and Texas, appointed by the Governor of each State, respectively. (3) Chair.--The Chair of the Task Force shall be appointed by the President from among the members under paragraph (2) who are Federal officials. (4) Duties of the task force.--The Task Force shall-- (A) consult with, and provide recommendations to, the Chair regarding the approval of State Coastal Ecosystem Restoration Plans; (B) coordinate scientific and other research associated with restoration of the Gulf Coast ecosystem; and (C) submit an annual report to Congress that summarizes the State Coastal Ecosystem Restoration Plans submitted by the Governors and approved by the Chair. (5) Application of the federal advisory committee act.--The Task Force shall not be considered an advisory committee under the Federal Advisory Committee Act (5 U.S.C. App.).

Gulf Coast Restoration Act - Establishes the Gulf Coast Ecosystem Restoration Task Force, which shall: (1) consult with, and provide recommendations to, the Chair of the Task Force regarding approval of State Coastal Ecosystem Restoration Plans submitted by the governors of Alabama, Florida, Louisiana, Mississippi, and Texas providing for restoration activities the Gulf Coast ecosystem adversely impacted by the blowout and explosion of the mobile offshore drilling unit Deepwater Horizon on April 20, 2010; (2) coordinate scientific and other research associated with restoration of such ecosystem; and (3) submit an annual report to Congress that summarizes the Plans approved by the Chair. Establishes in the Treasury the Gulf Coast Ecosystem Restoration Fund. Directs the Secretary of the Treasury to deposit into the Fund sums equal to not less than 80% of any amounts collected by the United States as penalties, settlements, or fines under the Federal Water Pollution Control Act (commonly known as the Clean Water Act) in relation to the Deepwater Horizon explosion and resulting hydrocarbon releases into the environment. Makes the Fund available for the conservation, protection, and restoration of the Gulf Coast ecosystem in accordance with approved Plans. Requires the governors of such states to: (1) submit a Plan to the Chair by October 1, 2011; and (2) solicit local input and provide for public participation in the development of the Plan. Requires the Chair to disburse amounts from such Fund to such a state for which the Chair has approved a Plan only for: (1) projects and activities for the conservation, protection, or restoration of coastal areas, including wetlands; (2) mitigation of damage to fish, wildlife, or natural resources; (3) planning assistance and the administrative costs of complying with this Act; and/or (4) implementation of a federally approved marine, coastal, or comprehensive conservation management plan.

CLOSE Detroit resident James Robertson, 56, of Detroit talks about his journey walking 21 miles a day to work and back. Ryan Garza/Detroit Free Press A story about a Detroit man who commutes about 21 miles a day on foot to and from work has spurred donations from across the nation. Buy Photo James Robertson, 56, of Detroit. (Photo: Ryan Garza, Detroit Free Press)Buy Photo A story about a Detroit man who commutes about 21 miles a day on foot to and from work has spurred reaction from across the nation, including social media fund-raisers that have netted more than $80,000 in donations as of 6:30 p.m. Monday. Because buses don't cover the full distance between James Robertson's home in Detroit and his job in Rochester Hills, he walks about eight miles headed to work and about 13 miles home, five days a week. His story — told by Bill Laitner in Sunday's Detroit Free Press — has inspired hundreds to offer money to buy him a car, pay his insurance and to provide professional help in managing the donations. Robertson said Sunday he was flattered by the attention he'd gotten for his arduous commutes after the Free Press published a front-page story about him -- and amazed that complete strangers would respond so generously, some by offering to buy him a new car and others offering to give him one. "Are you serious?" he said to a reporter after hearing of one crowd-funding effort alone that, by early Sunday night, had raised $30,000 — $25,000 more than the goal of the originator, a Wayne State University student. Evan Leedy, 19, of Macomb Township, a WSU student studying computer science, said he was struck by the article and by the sudden torrent of people commenting online, many of them asking how they could help Robertson. Leedy said he decided to act. "I just used my phone. I created the go-funding site and within an hour we had $2,000," he said. "I set the goal at the beginning of $5,000. Right now my page has more than $30,000" as of 6 p.m. Sunday, Leedy said. Two other people created GoFundMe sites, "so I contacted them so we could coordinate this, and they've raised $3,000," he added. Leedy said he wanted to take steps that would ensure that the money goes directly to Robertson and that publicity about it doesn't put him at risk of being pressured to share it. "And I think some of it should be set aside for his insurance and gas and maintenance," Leedy said. A Downriver car dealership offered to give him a 2014 Chevrolet Cruz or Sonic. "He gets to choose," said Angela Osborne, customer service specialist at Rodgers Chevrolet in Woodhaven. "We were just impressed with his determination," Osborne said. Sales manager Darwin Filey said he read about Robertson after a fellow Facebook friend shared the story with him. "When I saw the story I said 'wow.' Some people said you guys have got to do something. Then I called my owner and she read the story and said put something together," Filey said. He said Robertson would have to pay the tax on the car, which would be about $900. "We've never done anything like this at all. We've given to various causes but nothing at this magnitude," said Filey, who has been with the dealership for 2 1/2 years. More than a hundred others offered cash for a car, or their own cars, as well as bus tickets, bicycles and even daily chauffeur service for Robertson. "Monday is gonna be some bad weather and I don't want him making that trek," said Stuart Sutherland, a student at Oakland University who offered to donate cash in an e-mail. Joe Coppola, a technical recruiter for Optomi, wrote: "I want to give him my 2004 Chevy Cavalier. It runs well and is certainly better than not having a car." Honda North America, and David Fischer – owner of the Suburban Collection – offered "to keep Mr. Robertson in the Honda family by donating a vehicle to him." A man in Evanston, Ill., said he wanted to pay for a car and several years' worth of insurance. A self-employed man in Madison Heights said he would drive Robertson to work and home, each day, for free. Meanwhile, the modest Detroiter who walks an amazing 21 miles on his daily commutes to work in suburban Detroit said not even Sunday's snowstorm would keep him from getting to his job Monday. Eyeing the snow piling up around his white-frame house in Detroit, Robertson sounded not a bit worried. "I've had worse. This is reminiscent of those snowstorms last year, and I made it then," said the man with a perfect attendance record in more than a dozen years at Schain Mold & Engineering in Rochester Hills. Robertson said he likes walking and being outdoors, and prizes his job and coworkers, but he knows he can't keep up his arduous commuting forever. Robertson's aging Honda Accord quit on him in 2005, and after repeated cutbacks in bus service the walking segments of his daily commutes grew years ago to take more time than he spends in his eight-hour factory shifts molding parts. As for the possibility that a new federal program, available from Detroit's bus system, might provide a small-bus service that would pick Robertson up at home and deliver him directly to his job temporarily, he said: "I'd rather they spent that money on a 24-hour bus system, not on some little bus for me. This city needs buses going 24/7. You can tell the city council and mayor I said that." Like hundreds of other Detroiters, the cost of car insurance is a factor Robertson knows he will have to deal with in acquiring his own transportation. A nationwide survey conducted last week found car insurance in Detroit to be the costliest in the nation, at an average of about $5,000 a year. Darwin said it's not uncommon for Detroit motorists to have insurance premiums higher than car payments. "I'm not an insurance agent, if I'm guessing it's going to be about $2,200 for six months." He added insurance companies often provide discounts for a year's payment upfront. "I can work that insurance thing out," Robertson said. "It might be tough, but my dad used to say, tough times don't last — tough people do." UBS banker Blake Pollock, who befriended Robertson while stopped in Oakland County and has given him dozens of rides this winter, said he was thrilled but wary about the outpouring of donations. During his own commutes to his office in Troy, Pollock last year began noting Robertson's foot-slogging commutes, day after day, and finally offered him a ride. Now, they're fast friends. On Sunday, Pollock said he planned to set up a board "of several professionals" to oversee the donations rolling in for Robertson. "Putting a car in his driveway and just handing James the keys or filling his pockets with cash is not the answer. But with these resources now, we should be able to do something very positive for the guy," said Pollock, a vice president at UBS. "I think the hundreds of donors want this to go to James and not have this go out of his hands. So, if we can set up this little board to manage his money, I think that can happen. "When I'm with him tomorrow, I'm going to talk to him about that" — during the Monday-morning ride that Pollock planned to give Robertson after a bus gets him from Detroit to Troy. Contact Bill Laitner: [email protected] or 313-223-4485. Read or Share this story: http://on.freep.com/1BMTexd ||||| CLOSE James Robertson, 56, of Detroit has a champ's commute. He rides buses part-way but walks about 21 miles in round trips to a factory. Ryan Garza/Detroit Free Press He doesn't look athletic but James Robertson, 56, of Detroit has a champ's commute. He rides buses part-way but walks about 21 miles in round trips to a factory, unless his banker pal offers a lift. Buy Photo James Robertson, 56, of Detroit, makes his way along Crooks Road after working his shift at Schain Mold & Engineering in Rochester Hills on Friday, Jan. 9, 2015. (Photo: Ryan Garza Detroit Free Press)Buy Photo Story Highlights Think your commute is tough? Detroiter James Robertson, 56, walks about 21 miles a day, round trip. Robertson also takes a bus ride part-way to his hourly job in Rochester Hills, and part-way home. He says he loves his job and bosses, buses are limited and he can't afford a car on $10.55 an hour. Lately he catches breaks when a friendly banker heading for Troy sees him and offers frequent lifts. Leaving home in Detroit at 8 a.m., James Robertson doesn't look like an endurance athlete. Pudgy of form, shod in heavy work boots, Robertson trudges almost haltingly as he starts another workday. But as he steps out into the cold, Robertson, 56, is steeled for an Olympic-sized commute. Getting to and from his factory job 23 miles away in Rochester Hills, he'll take a bus partway there and partway home. And he'll also walk an astounding 21 miles. Five days a week. Monday through Friday. It's the life Robertson has led for the last decade, ever since his 1988 Honda Accord quit on him. Every trip is an ordeal of mental and physical toughness for this soft-spoken man with a perfect attendance record at work. And every day is a tribute to how much he cares about his job, his boss and his coworkers. Robertson's daunting walks and bus rides, in all kinds of weather, also reflect the challenges some metro Detroiters face in getting to work in a region of limited bus service, and where car ownership is priced beyond the reach of many. But you won't hear Robertson complain — nor his boss. "I set our attendance standard by this man," says Todd Wilson, plant manager at Schain Mold & Engineering. "I say, if this man can get here, walking all those miles through snow and rain, well I'll tell you, I have people in Pontiac 10 minutes away and they say they can't get here — bull!" As he speaks of his loyal employee, Wilson leans over his desk for emphasis, in a sparse office with a view of the factory floor. Before starting his shift, Robertson stops by the office every day to talk sports, usually baseball. And during dinnertime each day, Wilson treats him to fine Southern cooking, compliments of the plant manager's wife. "Oh, yes, she takes care of James. And he's a personal favorite of the owners because of his attendance record. He's never missed. I've seen him come in here wringing wet," says Wilson, 53, of Metamora Township. With a full-time job and marathon commutes, Robertson is clearly sleep deprived, but powers himself by downing 2-liter bottles of Mountain Dew and cans of Coke. "I sleep a lot on the weekend, yes I do," he says, sounding a little amazed at his schedule. He also catches zzz's on his bus rides. Whatever it takes to get to his job, Robertson does it. "I can't imagine not working," he says. 'Lord, keep me safe' The sheer time and effort of getting to work has ruled Robertson's life for more than a decade, ever since his car broke down. He didn't replace it because, he says, "I haven't had a chance to save for it." His job pays $10.55 an hour, well above Michigan's minimum wage of $8.15 an hour but not enough for him to buy, maintain and insure a car in Detroit. As hard as Robertson's morning commute is, the trip home is even harder. At the end of his 2-10 p.m. shift as an injection molder at Schain Mold's squeaky-clean factory just south of M-59, and when his coworkers are climbing into their cars, Robertson sets off, on foot — in the dark — for the 23-mile trip to his home off Woodward near Holbrook. None of his coworkers lives anywhere near him, so catching a ride almost never happens. Instead, he reverses the 7-mile walk he took earlier that day, a stretch between the factory and a bus stop behind Troy's Somerset Collection shopping mall. "I keep a rhythm in my head," he says of his seemingly mechanical-like pace to the mall. At Somerset, he catches the last SMART bus of the day, just before 1 a.m. He rides it into Detroit as far it goes, getting off at the State Fairgrounds on Woodward, just south of 8 Mile. By that time, the last inbound Woodward bus has left. So Robertson foots it the rest of the way — about 5 miles — in the cold or rain or the mild summer nights, to the home he shares with his girlfriend. Buy Photo The daily route of "the incredible commuter" James Robertson, 56, of Detroit. (Photo: Detroit Free Press) "I have to go through Highland Park, and you never know what you're going to run into," Robertson says. "It's pretty dangerous. Really, it is (dangerous) from 8 Mile on down. They're not the type of people you want to run into. "But I've never had any trouble," he says. Actually, he did get mugged several years ago — "some punks tuned him up pretty good," says Wilson, the plant manager. Robertson chooses not to talk about that. So, what gets him past dangerous streets, and through the cold and gloom of night and winter winds? "One word — faith," Robertson says. "I'm not saying I'm a member of some church. But just before I get home, every night, I say, 'Lord, keep me safe.' " The next day, Robertson adds, "I should've told you there's another thing: determination." A land of no buses Robertson's 23-mile commute from home takes four hours. It's so time-consuming because he must traverse the no-bus land of rolling Rochester Hills. It's one of scores of tri-county communities (nearly 40 in Oakland County alone) where voters opted not to pay the SMART transit millage. So it has no fixed-route bus service. Once he gets to Troy and Detroit, Robertson is back in bus country. But even there, the bus schedules are thin in a region that is relentlessly auto-centric. "The last five years been really tough because the buses cut back," Robertson says. Both SMART and DDOT have curtailed service over the last half decade, "and with SMART, it really affected service into Detroit," said Megan Owens, executive director of Transportation Riders United. Detroit's director of transportation said there is a service Robertson may be able to use that's designed to help low-income workers. Job Access and Reverse Commute, paid for in part with federal dollars, provides door-to-door transportation to low-income workers, but at a cost. Robertson said he was not aware of the program. Still, metro Detroit's lack of accessible mass transit hasn't stopped Robertson from hoofing it along sidewalks — often snow-covered — to get to a job. At home at work Robertson is proud of all the miles he covers each day. But it's taking a toll, and he's not getting any younger. "He comes in here looking real tired — his legs, his knees," says coworker Janet Vallardo, 59, of Auburn Hills. But there's a lot more than a paycheck luring him to make his weekday treks. Robertson looks forward to being around his coworkers, saying, "We're like a family." He also looks forward to the homemade dinners the plant manager's wife whips up for him each day. "I look at her food, I always say, 'Excellent. No, not excellent. Phenomenal,' " he says, with Wilson sitting across from him, nodding and smiling with affirmation. Although Robertson eats in a factory lunchroom, his menus sound like something from a Southern café: Turnip greens with smoked pork neck bones, black-eyed peas and carrots in a brown sugar glaze, baby-back ribs, cornbread made from scratch, pinto beans, fried taters, cheesy biscuits. They're the kind of meal that can fuel his daunting commutes back home. Though his job is clearly part of his social life, when it's time to work this graduate of Northern High School is methodical. He runs an injection-molding machine the size of a small garage, carefully slicing and drilling away waste after removing each finished part, and noting his production in detail on a clipboard. Strangers crossing paths Robertson has walked the walk so often that drivers wonder: Who is that guy? UBS banker Blake Pollock, 47, of Rochester, wondered. About a year ago, he found out. Pollock tools up and down Crooks each day in his shiny black 2014 Chrysler 300. "I saw him so many times, climbing through snow banks. I saw him at all different places on Crooks," Pollock recalls. Last year, Pollock had just parked at his office space in Troy as Robertson passed. The banker in a suit couldn't keep from asking the factory guy in sweats, what the heck are you doing, walking out here every day? They talked a bit. Robertson walked off and Pollock ruminated. From then on, Pollock began watching for the factory guy. At first, he'd pick him up occasionally, when he could swing the time. But the generosity became more frequent as winter swept in. Lately, it's several times a week, especially when metro Detroit sees single-digit temperatures and windchills. "Knowing what I know, I can't drive past him now. I'm in my car with the heat blasting and even then my feet are cold," Pollock says. Other times, it's 10:30 or 11 p.m., even after midnight, when Pollock, who is divorced, is sitting at home alone or rolling home from a night out, and wondering how the man he knows only as "James" is doing in the frigid darkness. On those nights, Pollock runs Robertson all the way to his house in Detroit. "I asked him, why don't you move closer" to work. "He said his girlfriend inherited their house so it's easy to stay there," Pollock said. On a recent night run, Pollock got his passenger home at 11 p.m. They sat together in the car for a minute, outside Robertson's house. "So, normally you'd be getting here at 4 o'clock (in the morning), right?" the banker asks. "Yeah," Robertson replies. Pollock flashes a wry smile. "So, you're pretty early, aren't you?" he says. Robertson catches the drift. "Oh, I'm grateful for the time, believe me," Robertson says, then adds in a voice rising with anticipation: "I'm going to take me a bath!" After the door shuts and Pollock pulls away, he admits that Robertson mystifies him, yet leaves him stunned with admiration for the man's uncanny work ethic and determination. "I always say to my friends, I'm not a nice guy. But I find myself helping James," Pollock says with a sheepish laugh. He said he's picked up Robertson several dozen times this winter alone. Has a routine At the plant, coworkers feel odd seeing one of their team numbers always walking, says Charlie Hollis, 63, of Pontiac. "I keep telling him to get him a nice little car," says Hollis, also a machine operator. Echoes the plant manager Wilson, "We are very much trying to get James a vehicle." But Robertson has a routine now, and he seems to like it, his coworkers say. "If I can get away, I'll pick him up. But James won't get in just anybody's car. He likes his independence," Wilson says. Robertson has simple words for why he is what he is, and does what he does. He speaks with pride of his parents, including his father's military service. "I just get it from my family. It's a lot of walking, I know." Robertson's commute by the miles Detroit City Hall to Metro Airport: What he walks each day Detroit to Lansing: What he walks each week Detroit to Louisville, Ky.: What he walks each month Detroit to Los Angeles – and back: What he walks each year Read or Share this story: http://on.freep.com/1CNbtXf

– At 8am, it's time for James Robertson, 56, to leave for work—for a job that starts at 2pm. That's because he makes much of the 23-mile journey on foot, resulting in a 21-mile round-trip walk every day, the Detroit Free Press reports. His car broke down about a decade ago and he's been walking ever since, combining the slog with bus rides in the few areas where buses are available. Once he's worked from 2pm to 10pm, he heads home again in the dark, normally arriving around 4am. With some buses shut down for the day by that point, he walks a total of 13 miles, the Free Press notes. Faith and determination keep him going, he says. He was mugged once, his boss says, though Robertson himself only mentions that he walks through some dangerous areas. But the many miles have their benefits: He loves his co-workers, and his boss's wife cooks him dinner every night. "She takes care of James. And he's a personal favorite of the owners because of his attendance record," says the plant manager at Schain Mold & Engineering. That record is perfect. "I set our attendance standard by this man," the manager says. And this story has a happy ending. Now that Robertson's story is known, people are coming to his aid. Yesterday's front-page Free Press story spurred a number of crowdfunding efforts, which as of last night had brought in more than $30,000, the paper reports. Others offered him rides. Robertson's reaction when the paper told him: "Are you serious?"

the extremely large telescopes ( elt)the european extremely large telescope ( e - elt ) , the thirty meter telescope ( tmt ) , and the giant magellan telescope ( gmt)will reach unprecedented depths at optical and infrared wavelengths and have unprecedented spatial resolutions on account of their enormous apertures . to fully exploit the potential `` @xmath2 '' benefit of these facilities , taking advantage of both depth and resolution , requires adaptive optics ( ao ; see @xcite for a comprehensive review ; see @xcite for discussion relating to tmt and @xcite for discussion relating to e - elt ) . this technology improves the strehl ratio of the point - spread function ( psf ) , a measurement of the peak of the psf relative to the theoretical diffraction - limited value . it does this by correcting the wavefront distortions in the science light caused by the atmosphere . adaptive optics has a better performance at longer wavelengths and so they generally operate at near - infrared ( nir ) wavelengths . in classic adaptive optics , optical aberrations are first measured in the direction of a point - like source above the turbulence by using a wavefront sensor . natural guide stars ( ngs ) are the best sources to use since they are distant and point - like . however , there can be not enough suitable ( i.e. , bright ) ngss in a given field of view , leading to the use of artificial laser guide star ( lgs ) . these are created by a laser beam launched from the proximity of the telescope in the direction of the science target . a return of photons toward the telescope aperture is produced by either rayleigh scattering from molecules in the atmosphere or by excitement of sodium atoms at high altitudes . since the lgs wavefront sensors are blind to the tip - tilt aberration @xcite , ngss are still necessary but they can be fainter because they are required only to determine tip and tilt . a control system acquires the data from the wavefront sensors and calculates the correction that the ao system has to apply . a deformable mirror then injects an equal and opposite distortion to correct the image . the main shortcoming of classical ao is the limited size of the corrected field , typically of the order of a few arcseconds . a single guide star can probe only the cylinder of atmosphere in its direction ; the more distant a target is from it , the less the guide star probes the relevant aberrations and so the less effective the correction . this effect , known as anisoplanatism , is improved by multi - conjugate adaptive optics ( mcao ) . here , multiple guide stars are employed to probe the atmosphere in different directions and reconstruct the atmospheric distortion in a larger volume . multiple deformable mirrors , optically conjugated to different altitudes , apply the correction to the layers of turbulence associated to those heights . while an mcao system can work using only ngss , such as the mcao demonstrator mad on vlt @xcite , the use of lgss is advantageous because it alleviates the requirements for an asterism of bright stars close to the scientific target , thus increasing significantly the sky coverage . the gemini multi - conjugate adaptive optics system ( gems ) on gemini south is the first facility class mcao instrument , and had first light in 2012 . high resolution imaging of extended crowded stellar fields has generally been a prerogative of space telescopes , but gems now routinely enables this capability from the ground . we have observed the galactic globular clusters ngc 1851 , ngc 2808 , ngc 5904 , ngc 6652 , ngc 6681 , and ngc 6723 in the j and k@xmath0 bands . these clusters were selected as southern hemisphere targets which had preexisting , high quality , space - based imaging from the hst acs survey of galactic globular clusters of @xcite . first results for ngc 1851 are presented in @xcite and results for ngc 2808 and ngc 6681 are published in @xcite . in addition to the study of their stellar populations and dynamics , a major goal of our observing program is to better understand how best to exploit mcao data for precision photometry and astrometry , in order to prepare for science observations with the elts . the large number of relatively bright point sources distributed over the field of view allows our globular clusters to be used as a training ground for measurement techniques on mcao data . the success of mcao as a technology relies on its ability to produce science - ready astronomical measurements particularly photometry and astrometry and so it is important to use science - based metrics to judge the success or otherwise of any techniques . in this paper , we examine the critical question of how to extract the most precise photometry from mcao data , using our observations of ngc 1851 . like most globular clusters , ngc 1851 has a thin main sequence and giant branch but has a split subgiant branch @xcite . examination of the quality of the color magnitude diagrams will allow us to determine the utility of the strategies that we employ to obtain the photometry . while our conclusions are specifically valid for gems , they are also expected to be of relevance for any mcao dataset , and it is our expectation that such studies will prove useful for the development of the mcao systems and observing strategies for the tmt and e - elt . a subsequent contribution will present similar details for astrometric measurements , noting that the capacity of gems to produce precise astrometry has already been shown in @xcite . the format of this paper is as follows : section [ sec : observations ] discusses the details of our observations of ngc 1851 ; section [ sec : images ] presents a summary of the image processing ; section [ sec : performance ] overviews the photometric performance of gems / gsaoi , especially regarding the uniformity of the shape of the psf ; section [ sec : photometry ] presents an overview of our photometric analysis procedure and a detailed discussion of the steps taken to optimize the process to obtain the most precise photometry ; section [ sec : cmds ] presents our final color - magnitude diagrams and a brief discussion of their most prominent features ; section [ sec : conclusion ] summarises our main conclusions . gems , the gemini multi - conjugate adaptive optics system @xcite , is the first facility - class mcao system . it started science operations at the end of 2012 on the 8-meter gemini south telescope on cerro pachn ( chile ) . it measures the aberrations caused by the volume of atmosphere in the direction of the observed field using five laser beams , tuned to the sodium d2 line at 589 nm , that are launched from the back of the secondary mirror . by exciting the layer of atmospheric neutral sodium at 90100 km @xcite , the system generates five lgss arranged in a 60 square asterism with the fifth star in the center . a wavefront sensor ( wfs ) for each lgs measures the wavefront distortions along these five directions . since the lgs wfss are blind to tip - tilt aberrations @xcite , 13 bright natural guide stars ( ngss ) are required to determine this low - order mode , each with their own wfs . all wavefront measurements are combined to calculate the commands given to the deformable mirrors that provide the correction . the two deformable mirrors are optically conjugated to 0 and 8.5 km to correct for the turbulence at the ground and at high altitudes , respectively . the corrected wavefront is imaged by gsaoi , the gemini south adaptive optics imager @xcite . this camera has four teledyne hawaii-2rg nir detectors @xcite arranged in a 2 x 2 array , each chip with 2040 x 2040 active pixels . the pixel scale is 0.0196px@xmath3 and the total field of view is 82.5 x 82.5 ( with a gap of 2.5 between the chips ) . the detectors are read out using fowler sampling @xcite , which consists of a series of nondestructive reads of the pixels at the beginning and at the end of each exposure . the two sets are averaged and their difference constitutes the signal accumulated . the larger the number of samples taken , the lower the read noise . during the gems / gsaoi science verification period , we observed the galactic globular cluster ngc 1851 ( 05@xmath414@[email protected] , -400247.6 ) with the nir broad band filters j ( @xmath7 ) and k@xmath0 ( @xmath8 ) on the nights of 2012 december 31 , 2013 january 27 , and 2013 january 30 ( gemini program gs-2012b - sv-406 , pi : mcconnachie ) . sub - exposures of 160 seconds were used and dithered in a pattern of 3 steps to cover the gap between the four chips ( figure [ fig : dithering ] ) . seventeen exposures were taken in the j band and twelve in the k@xmath0 . two shorter exposures were also taken in each band to obtain non - saturated photometry of the brightest stars . table [ tab : exposures ] provides a summary of our exposures . we used the `` faint object '' read mode with four fowler samples per set ( read noise of 13.6 @xmath9 ) . three natural guide stars in the field of view have been used for the tip - tilt correction , with magnitudes of 13.3 , 13.7 , and 14.4 in the r band . unfortunately , reliable measurements of the seeing conditions at the telescope site during our individual observations were not recorded . however , measurements made on cerro tololo by the ctio robodimm indicate relatively poor seeing conditions , with median values of approximately 1.1 and 0.8 when taking the j and k@xmath0 exposures , respectively . one of the j band images ( exposure # 10 ) has not been used in the data analysis because of its particularly poor mcao correction . a single k@xmath0 band exposure is shown in figure [ fig : mosaic ] with the positions of the natural and laser guide stars highlighted . the same pattern was used for the 17 j band long exposures , with 5 of the pointings repeated.,scaledwidth=60.0% ] .observing log of ngc 1851 with gems [ cols="^,^,^,^,^",options="header " , ] exposure of 160 seconds of ngc 1851 with gems / gsaoi . the orange star symbols show the position of the five lgss . the three ngss used are circled in red.[fig : mosaic],scaledwidth=40.0% ] prior to performing the photometric analysis , we process the raw images with the gemini / gsaoi iraf package correcting for bad pixels , linearity and flat fielding . * _ bad pixels _ the gsaoi detector has a large number of both dead and bright pixels . the defective elements have been flagged using the bad pixel map provided by the gemini iraf package . most of the hot pixels also cause an uncorrected leak of signal towards adjacent pixels that have lower counts , producing a `` cross - like '' pattern as shown in figure [ fig : capac ] . these are evident especially in the j band exposures due to the lower sky emission . this effect is caused by inter - pixel capacitance @xcite , an additional voltage on a pixel during its reading that is generated by the large difference in collected charges with respect to an adjacent one . * _ linearity _ hawaii-2rg chips deviate appreciably at high signal levels from a linear response because of the change in the reverse bias voltage caused by the accumulated charges @xcite . to compensate for this behavior , the values of every pixel are corrected with a quadratic polynomial whose coefficients were measured during the gsaoi commissioning @xcite . * _ flat field _ to create our flat fields in each band , we first produced a master dome flat and a master twilight flat by median - combing individual exposures using average sigma clipping . the dome flats have the benefit of a high signal to noise , although their spectral signature and uniformity is inferior to the sky flats . the latter are therefore preferred but also have a lower signal to noise than the dome flats . thus , we combine the dome and twilight master flats together to create a `` super '' flat in the following way . we first divide the master twilight by the master dome and we apply on the result a top - hat median circular filter to keep only the large - scale spatial variation . this creates a low - pass filtered image that is then multiplied by the dome master flat that has information on the pixel - to - pixel difference in response . the resulting `` super '' flat has the high signal - to - noise of the dome exposures and the uniform illumination and spectral signature of the twilight exposures , making it our choice for the flat fielding of the science exposures . , scaledwidth=40.0% ] we note that the detectors have a very low dark current ( 0.01 @xmath9 s@xmath3 px@xmath3 ) . the scale of this effect is of the order of one electron per pixel in our longest exposures ; hence , no dark frame has been subtracted . we also highlight that we do not apply sky frames . the focus of our analysis is point source photometry and , on the spatial scale of a psf , the flux from the sky is expected to be constant . applying a sky frame introduces additional systematic uncertainties and contributes to the photon noise . instead , we evaluate the sky at the position of each star using an annulus around them during the profile fitting , as discussed in section [ sec : photometry ] . an example region ( 4 x 3.3 ) of one of the k@xmath0 exposures before and after processing is shown in figure [ fig : iraf ] . the purpose of mcao is to provide diffraction - limited imaging over the largest field of view possible . in the case of a perfect correction , the psfs across the field would have the same size , shape , and flux concentration . globular clusters provide an ideal testing ground of mcao systems in this regard , with a large number of stars to examine . we now characterize the quality and stability of the mcao correction in our exposures to inform the more detailed photometric measurements that are described in section [ sec : photometry ] . we use the large number of bright and isolated psf stars ( see discussion in section [ sec : psfestimate ] ) , distributed across the field of view . we subtract all other stars from the images ( using the technique described in section [ sec : photometry ] ) and we apply a median filter on the bad pixels to remove them from the images . an example of a stellar image is shown in the left panel of figure [ fig : interp ] . the stellar images are then interpolated onto a finer grid by zero - padding their fourier transform by a factor of 3 , an example of which is shown in the right panel of figure [ fig : interp ] . the strehl ratio ( sr ) is the ratio of the peak flux of the actual psf to the peak flux of the diffraction - limited psf . to measure it , we adopt the peak value of the interpolated image as the peak of the psf . the diffraction - limited psf is generated by the fourier transform of the gemini south telescope aperture , which we model as a circle with a diameter of 8.1 m and a central circular obstruction of 1 m. we omit the spider of the secondary mirror since the change in the psf peak by including this more complex structure is negligible . the diffraction peak is normalized to the flux of the star using the instrumental magnitudes measured by psf fitting by the techniques in section [ sec : photometry ] . however , the psf model we use here has a radius of 45 pixels that is larger than the radius used in section [ sec : psfrad ] this is so that we include in each measurement the majority of flux from the star ( see figure [ fig : psfradstat ] ) . this improves the accuracy of the flux , at a cost to the precision , by avoiding larger systematic errors . we provide a simple quantification of the two dimensional shape of the psf by fitting an ellipse to the contour that defines the half - maximum of the psf . an illustration of this is shown in the right hand panel of figure [ fig : interp ] . the fwhm is then defined from the geometric mean of the semi - major ( @xmath10 ) and semi - minor ( @xmath11 ) axes , such that fwhm @xmath12 , and the ellipticity is defined as @xmath13 . we also measure the position angle of each ellipse . this allows us to create spatial performance maps of the mcao correction , an example of which is shown in figure [ fig : spline ] for one of the long k@xmath0 exposures ( exposure 10 ) . the left panel shows the distribution of raw sr measurements for each of the psf stars . note that there is a lack of psf stars in the central region of the image due to extreme crowding . the right panel shows the same performance map but interpolated across the full field using a smoothing spline and shown as a contour map . the average values of the fwhm , strehl ratio , and ellipticity of each long exposure image for both the j and k@xmath0 bands are shown in figure [ fig : perfstats ] . these exposures are numbered sequentially in the order that they were taken . the average fwhm in the j band is @xmath14 and in the k@xmath0 band is @xmath15 . for the strehl ratio , the average value for the j band is @xmath16 , whereas for the k@xmath0 band it is @xmath17 . it is expected that adaptive optics performs in k@xmath0 band better than in j since the aberrated wavefront has a larger spatial and temporal coherence at longer wavelengths @xcite . bands ( blue and red , respectively ) . the diffraction - limit fwhm values are shown in the top panel for comparison . we have not analyzed exposure # 10 in the j band due to a particularly poor mcao correction . these exposures are numbered sequentially in the order they were observed ; all k@xmath0 band exposures were observed on the same night , whereas the j band exposures were observed on two different nights , with the first ten observed on the first night.[fig : perfstats],title="fig:",scaledwidth=50.0% ] bands ( blue and red , respectively ) . the diffraction - limit fwhm values are shown in the top panel for comparison . we have not analyzed exposure # 10 in the j band due to a particularly poor mcao correction . these exposures are numbered sequentially in the order they were observed ; all k@xmath0 band exposures were observed on the same night , whereas the j band exposures were observed on two different nights , with the first ten observed on the first night.[fig : perfstats],title="fig:",scaledwidth=50.0% ] bands ( blue and red , respectively ) . the diffraction - limit fwhm values are shown in the top panel for comparison . we have not analyzed exposure # 10 in the j band due to a particularly poor mcao correction . these exposures are numbered sequentially in the order they were observed ; all k@xmath0 band exposures were observed on the same night , whereas the j band exposures were observed on two different nights , with the first ten observed on the first night.[fig : perfstats],title="fig:",scaledwidth=50.0% ] in figure [ fig : perfmaps ] , we show the performance maps for the best of our exposure ( # 8 in the k@xmath0 band ) , which has the smallest fwhm , the largest strehl ratios , and the most circular psfs . the first three panels show the interpolated maps of the fwhm , sr , and ellipticity . the fourth panel indicates the shape of each fwhm ellipse , where the angle of the dash indicates the position angle and the length indicates the ellipticity ( short dashes are more circular ellipses and thus the position angle is not as well measured as for longer dashes ) . in all four panels , it is clear that the performance is relatively uniform but certainly not constant across the field . in line with expectations , the best values of fwhm and sr are near the center of the lgs asterism . but we also notice that the shape of the psf , described by its ellipticity , has a more complex spatial pattern and does not perform better in the center ( thus our best exposure has smaller but more elliptical psfs in the center of the asterism compared to elsewhere ) . indeed , we find that the behavior of the ellipticity and position angles varies abruptly in consecutive exposures , as demonstrated in figure [ fig : elliptmaps ] for three consecutive k@xmath0 band exposures . note that this does not correlate with the movement of the ngs asterism caused by the dithering of the telescope . one of the main problems in delivering a better performance was the incorrect conjugation in altitude of the optical elements in the lgs wavefront sensors , as documented in a gemini observatory internal report ( g. sivo , private communication ) . this was identified and corrected in the year after our observations . despite these few issues , our mcao observations show a substantial improvement from seeing - limited images . our estimation of the performance of gems are consistent with previous findings @xcite . we now demonstrate that they can produce unprecedented levels of photometric precision in a crowded field from the ground . it is well know that precision photometry in a crowded stellar field can not be achieved by aperture photometry due to crowding , where starlight from one star compromises the measurement of the flux of any nearby star . a more robust method is profile fitting photometry , especially if the psf can be estimated empirically on the images . this is the case for our observations of ngc 1851 , where we have a large number of bright point - like sources in every part of the field of view . for the ensuing photometric analysis we have used the daophot ii suite of programs @xcite . we begin by providing a broad overview of the process that we use to obtain our photometry prior to discussing how certain critical stages of our analysis are optimized for best performance . * the stars are first detected ( using the find routine ) by convolving each individual image with a truncated gaussian profile , lowered to have a zero integral and that has a fwhm similar to that of the real psf . local maxima in the convolved images are identified as stars if they are above a chosen noise threshold ( @xmath18 for j and @xmath19 for k@xmath0 ) and within a range of `` sharpness '' and `` roundness '' parameters , selected to discriminate a star from extended objects , cosmic rays or artifacts of the detector . * for each catalog corresponding to each of the original images , we transform the coordinate system to a master frame of reference ( using the daomaster program ) . the master frame is defined by the seeing - limited catalog used for the photometric calibration ( section [ sec : calibration ] ) . a polynomial transformation of order 3 * we additionally stack the long exposure images ( using montage ) by assigning to each pixel of the stacked image the median value of its nearest pixel from each of the transformed frames , and identifying all sources ( using find ) . while the resulting image has a larger psf than any of the single exposures ( due to the different psfs of each image , see section [ sec : performance ] , and the nearest - pixel approach instead of interpolation ) , these stacked images allow us to detect and measure a large number of faint stars that are not detected in the individual exposures ( figure [ fig : stack ] ) . * the master catalog is created in each band by combining all detections found in each of the short exposures , the stacked images , and in at least three of the dithered long exposures . the short exposures are primarily used to find the brightest unsaturated stars , the stacked images are primarily for the faintest stars , and the long exposures are for all the other sources , with the requirement of three independent detections to remove most spurious objects . * we select 500 `` psf stars '' in the entire field of view , approximately 90 in each quadrant of the detector ( left panel of figure [ fig : psf_stars ] ) , that are used to model the psf independently for every chip of every exposure . these are stars that are bright but not saturated and that do not have obvious close companions . they are chosen to be distributed as uniformly as possible across the observed field of view , except in the cluster core where many saturated stars cause large flux gradients that render reliable background estimates difficult . the significant number of psf stars ensures that the photon noise in the psf model is reduced and that systematic effects on individual psf stars ( such as detector cosmetics or contamination from unrecognized companion stars ) are minimized . a constant background is estimated for each psf star as the modal value of the pixels in a surrounding annulus and is then subtracted from each psf star . we choose the inner edge of this sky region to start from the pixel immediately outside the psf model and the outer edge to contain approximately 2000 pixels in the annulus . * the psf is modeled in two parts . the first component is a simple analytic function , for which we have chosen a lorentzian . the second component is a two dimensional grid of empirical corrections calculated from the residuals of the psf stars after subtracting the analytic component . this look - up table can be set to have either the same values everywhere in the field of view or to vary spatially . in the spatially varying case , each element of the table is associated with a set of coefficients that describe a bivariate polynomial in x and y , the position on the field of view . in section [ sec : performance ] , we demonstrated that there is significant spatial variation in the psf in our images , and so we have chosen to use a cubic polynomial , the highest degree of variability available in daophot . the possibility to calculate such a high variability is given by the large number of psf stars available in the images . photometric measurements are obtained for objects in each image , including the stacked images , by fitting the appropriate psf model to each object in the master source catalog ( using allstar ) . at each iteration , the flux of a star is calculated by first subtracting the profiles of its neighbors using their positions and magnitudes derived from the previous iteration ( starting with estimates from aperture photometry ) . the star s background ( as estimated from the previous iteration ) is then subtracted and the instrumental magnitude is measured by fitting the psf model to the star s central pixels within three fwhma , where the s / n is higher . the sky beneath the star is then updated by removing the star itself and measuring the values in an annulus starting at two pixels from the peak ( to avoid the large residuals of the core ) out to the edge of the psf model . the photometric calibration of the instrumental magnitudes is performed with respect to the 2mass photometric system . however , we have had to use an auxiliary catalog to connect our observations to the 2mass point source catalog , since the latter has only about 150 stars in the field and most of them are too bright for our exposures . this auxiliary catalog has been obtained by one of the authors ( pbs ) from 256 seeing - limited archival images of ngc 1851 ( median fwhm of 1.32 ) taken with the newfirm instrument on the blanco telescope on cerro tololo ( chile ) , and has a depth intermediate between our gemini images and the 2mass catalog . by matching the stars in the auxiliary catalog to the corresponding stars in our gemini dataset , we are able to determine the zeropoints of each chip in each exposure in both bands by using the technique described in section [ sec : calibration ] . the final step is to clean the calibrated j and k@xmath0 catalogs of spurious objects , extended objects , or poor photometry . to do this , we use the various photometric parameters calculated by daophot . specifically , we use : @xmath20 , the goodness of the photometric fit that is measured by the ratio between the fitting residuals and the expected scatter caused by noise only ; sharpness , which is derived from the difference in width between the object and the psf ( objects that are too small are usually bad pixels or cosmic rays , objects that are too large are usually galaxies ) ; the magnitude error , which is a combination of the estimated random noise and the fitting residuals ( weighted toward the bigger of the two ) . the left panels of figure [ fig : cmdclean ] show the cuts applied to these three parameters in both bands . the right panel of figure [ fig : cmdclean ] shows the two dimensional distribution of the difference in position of matched objects between the two bands . we remove from the final catalog those stars with more than 0.01 of discrepancy , corresponding to half a pixel . thus , our final catalog contains only high quality detections in both bands . the preceding subsection provided a high level overview of the methodology for obtaining the final photometry from our processed images . we have followed a standard procedure for psf photometry that has been implemented on optical and near ir observations of stellar fields for many years . however , science quality mcao observations of crowded fields are a relatively new capability and a major focus of this work has been to understand what modifications and subtleties are required at various stages in the process to have confidence that the final photometry is optimal . in particular , our analysis in section [ sec : performance ] demonstrates that the images still have significant distortions present that change the shape of the psf across the field and between exposures in a complex fashion . what follows is a discussion of what we have identified as critical steps and decisions in the method described in the previous subsection , to obtain the highest quality photometry . specifically : 1 . size of the psf model 2 . variability of the psf 3 . selection of the sky annuli 4 . minimizing contamination light in the psf stars 5 . independent profile fitting most of these items are judged by science - based metrics based on the quality of the final color magnitude diagram , instead of using parameters like fwhm and strehl ratio that are difficult to measure and do not translate easily into an impact for the science . calibration is discussed independently in section [ sec : calibration ] . in this discussion we show results stemming from the analysis in the k@xmath0 band , but we note similar results with the j filter . the psf model in daophot is defined within a radius ( termed the `` psf radius '' ) measured from the centroid . in the case of no variation in the psf across the field , this aperture will contain the same fraction of flux for every star . in this way , the flux measured within the psf radius for each star can be translated into a total flux via an additional term in the photometric zeropoint measured during the calibration ( section [ sec : calibration ] ) . in the case of a spatially variable psf , the psf radius should ideally contain most of the spatially variable component , so that the flux within the aperture is still a constant fraction of the total . ideally , the psf radius should also be large enough to include most of the real psf . in this way , when the star is subtracted during the profile fitting , all its flux is removed from the image and it does nt contaminate the profile of nearby stars . most of the spatial variability in the psf of mcao images is caused by an inhomegeneous correction applied over the field of view . the maximum spatial frequency of the aberrated wavefront that an mcao system can correct is @xmath21 , where @xmath22 is the pitch of the highest density of actuators in the deformable mirrors projected on to the aperture of the telescope . for gems it is @xmath23 @xcite . the mcao system behaves as a high - pass filter for the wavefront , such that only light within the `` control radius '' , @xmath24 , of any psf is affected by the correction , leaving the wings of the profile mostly unchanged with respect to the seeing - limited psf . since the actuators are actually arranged on a square grid , the psf region influenced by the adaptive optics for gems is a square with a side of @xmath25 . for gems , @xmath26 in k@xmath0 band and the psf radius used for our images should therefore , in principle , be at least this value . examination of a typical psf in our images suggests that this argument is valid . figure [ fig : rad ] presents an example of a stellar radial profile from our data . the left panel shows the two dimensional image , with the centroid marked by the green cross and a blue square superimposed with sides of @xmath27 . shown for reference is also a circle with a radius of 50 pixels . the right panel shows the radial profile of the psf , where each dot corresponds to a pixel in the image . firstly , we see that the profile does not level off to a constant value until around 50 pixels . secondly , the spread in the profile at small radius is significant and increases with decreasing radius . this is to be expected if the psf is significantly distorted ( e.g. , has significant ellipticity ) . as the inset panel shows , however , the spread in the points becomes broadly constant at a radius greater than 2122 pixels . this is in line with expectations from our argument above and confirms that the asymmetric part of the psf is mostly within the control radius . we have tested the effect of modifying the psf radius on the resulting photometry from our images . we have produced several different photometric catalogs , where each version uses a different value for the psf radius . all other steps in the photometric analysis are identical . we have combined the resulting instrumental magnitudes with the high precision photometry from the hst / acs catalogue of ngc 1851 in the v band ( f606w ) presented in @xcite . since this catalog is extremely precise , examination of the relative quality of the resulting optical - nir cmds allows us to develop a science based metric to judge the quality of our nir photometry . figure [ fig : psfradcmd ] shows the cmds corresponding to each version of our k@xmath0 photometry ( a similar analysis was made for the j band ) . we use the width of the main sequence turn - off ( msto ) , in the region where the sequence is nearly vertical , as a metric on the quality of the photometry . we quantify the width of this sequence via the fwhm of a gaussian curve fitted to the histogram of the color distribution of the stars . photometric errors and systematics will act to increase the measured width of the main sequence , even in the presence of multiple populations ( as is the case for ngc 1851 , see section [ sec : cmds ] ) , thus higher quality photometry will produce a smaller fwhm . we note that figure [ fig : psfradcmd ] uses uncalibrated k@xmath0 magnitudes . therefore , each cmd is shifted horizontally with respect to the others since the instrumental magnitudes are `` fainter '' when a smaller psf radius is used . the histograms in figure [ fig : psfradcmd ] demonstrate that the width of the msto in the cmd is minimized for psf radii of @xmath28 ( a psf radius of 24 pixels also appears to produce a narrower red giant branch ) . we find that this result holds for all exposures , independent of the quality of the ao correction applied . it is clear , therefore , that the optimal psf model radius for our analysis is close to the value of the control radius @xmath29 , which itself is considerably smaller than the `` overall '' size of the psf . figure [ fig : psfradstat ] plots the uncalibrated color of the msto as a function of the psf radius , and it is clear that the color does not change significantly ( i.e. , the instrumental k@xmath0 magnitude is constant ) for a psf radius between 40 and 50 pixels ; this value is also consistent with our discussion relating to figure [ fig : rad ] . image . the width of the sequence is represented by the error bars.[fig : psfradstat],scaledwidth=60.0% ] the flux outside the control radius is the same fraction for every star since all the variability in the shape of the psf is interior to this value . moreover , at large radii , where the intrinsic flux from the star is low , contamination due to noise , cosmic rays , and nearby stars can be significant ( for example , note the presence of several structures at large radii from the center of the bright star shown in figure [ fig : rad ] ) . adoption of a large psf radius means that these spurious structures are considered part of the psf model , leading to an overall reduction in the precision of the photometry . this is illustrated in figure [ fig : psfs ] , where the first panel shows the psf of a star observed in the k@xmath0 filter . the second and third panels are the two psf models for this star , where the former adopts a psf radius of 24 pixels and the latter a radius of 40 pixels . the latter model has a large amount of small scale structure at large radii that are not intrinsic to the halo , expected to be smooth for these long exposure times . thus , a psf radius close to the control radius is large enough to include all the variability of the psf but small enough to exclude the majority of spurious structure , leading to more precise photometry . an unwanted side effect of using a smaller value of the psf radius is that when a star is subtracted from the image during the profile fitting , it leaves an `` orphan '' halo with a hole in the center where the core of the psf was . the inner edge of the halo of a bright star looks like a doughnut , as shown in figure [ fig : halo ] . this discontinuity in brightness can lead to spurious detections , as is visible in figure [ fig : halo ] . however , these spurious detections are easily identified and removed from the final catalog during the quality control phase ( section [ sec : quality ] ) . , scaledwidth=30.0% ] in seeing - limited and space - based images , the psf is generally uniform across the field . any variability that does exist is usually a result of static and quasi - static distortions introduced by the optics , with no significant variation between observations . in contrast , in mcao data the psf can present a complex spatial and temporal variability in terms of size and overall shape , as demonstrated in section [ sec : performance ] , especially figure [ fig : elliptmaps ] . such distortions are much less over large fields than using classic ao but they still necessitate careful modeling to obtain accurate photometry . daophot uses for the psf a constant analytical function for all stars in combination with a two dimensional lookup table for the empirical corrections to create the model psf . each pixel in this grid can be set to have either the same values everywhere in the field of view or to vary spatially . in the spatially varying case , each element of the grid is associated with a set of coefficients that together describe a bivariate polynomial in x and y , the coordinates of the star in the field . the polynomial can be up to the third order , making the psf vary linearly , quadratically or cubically . we also note that each grid element varies independently of every other one . the top panel of figure [ fig : psfvarsub ] shows examples of six psf stars in a k@xmath0 image from different parts of a frame . the other panels show the same regions after profiles with different variability have been fitted and subtracted . the constant and linear models present large residuals , while the quadratic and cubic seem to fit similarly well the profiles . to determine which produces the most accurate photometry , we have created uncalibrated cmds ( figure [ fig : psfvarcmd ] ) as in section [ sec : psfrad ] to analyze the width of their mstos . on all the tested images we find that the cubic variability has similar or slightly better performance than the quadratic , which is unsurprising given the large distortions of the psfs that we observed in section [ sec : performance ] . when testing the psf radius we have also modified two related sets of radii . the first is the annulus of pixels that we haveused to measure and remove the sky value of the psf stars , measured beyond the psf radius ( see section [ sec : photometry ] ) . the second set is the annulus to calculate the sky during the profile fitting that is computed at every iteration after the profile subtraction and which is measured interior to the psf radius . the inner radius of this annulus is set at two pixels from the center to avoid the large residuals that could be near the peak . we have first tested the influence of the psf model s sky annulus on the photometry by varying its distance from the edge of the psf radius and its width . we have tried three annuli with inner and outer radii of [ 25 , 36 ] , [ 41 , 49 ] , and [ 25 , 49 ] , each of which include at least 2000 pixels to have a good signal . the first and third of these options measure the sky relatively close to where the psf is measured ( but with a larger area used in the latter option ) , whereas the second option measures the sky away from the psf to reduce any contribution to the flux from the psf star . using the same cmd dispersion criterion of section [ sec : psfrad ] , we found no measurable change in the photometric precision for any of the three photometric catalogs . we therefore adopted the first of the three choices . for the sky annulus used during profile fitting , we have tested an outer radius of 16 , 20 , and 24 pixels . for most of the images in k@xmath0 filter , the photometric precision does not measurably change . however , for the k@xmath0 exposures with poorer mcao correction and for all the j band exposures we tested , we find that a small outer radius is preferable , as is shown in figure [ fig : psfskycmd ] . we have therefore adopted a sky annulus with an inner radius of 2 pixels and an outer radius of 16 pixels . we postulate that a small outer radius is preferred because , when the strehl ratio is lower , more faint stars are left undetected . a larger outer sky radius then increases the chances of these faint stars contributing to the `` sky '' measurement , reducing the accuracy of this measurement . in a crowded image , the psf is inevitably going to be measured using stars that have their profiles contaminated by nearby sources , causing inaccuracies in its estimation ( for example , see the left panel of figure [ fig : rad ] ) . to improve the resulting model , we have performed an iterative estimation of the psf . namely , we measure a first estimate of the psf on the crowded image ( first iteration ) and with it we subtract all the stars from the image except for the psf stars . we then use this `` cleaned '' image to redetermine a better psf ( second iteration ) . figure [ fig : psf_stars ] shows an example of an original reduced frame and a `` cleaned '' one , where the psf stars are marked . by measuring the width of the msto in the usual way , we determine that there is a gain in photometric precision when using the psf estimated in the second iteration compared to the first ( figure [ fig : psfitercmd ] ) . no benefit has been observed from increasing the number of iterations that we use beyond two . the allframe task in the daophot suite can perform the profile fitting photometry on multiple images at the same time . at each iteration , this program uses the geometric transformations of each frame on the master catalog to determine the position of the stars on the images . then the psf models are centered on these positions and are fitted to the image by subtracting the nearby stars determined in the previous iteration . the estimated residuals in the positions of the stars are minimized in the following iterations by adjusting both the stars positions in the master catalog and the coefficients of the geometric transformation . by fixing the positions of the stars in the reference frame for all the images , the combined photometry is potentially more precise by reducing the uncertainty caused by the noise in positioning the fitted psf . in figure [ fig : alsalf ] , the first panel shows a region of a k@xmath0 band image near the edge of the field . the middle panel shows the subtracted image once all the psfs have been fitted without placing constraints on their positions from the master catalog . the right panel shows the subtracted image where the positions of the stars are fixed using the allframe transformation . clearly , the latter image displays strong residuals caused by a similar misplacement of the psf centers . we note that the region selected for this example is one where the effect is particularly dramatic and that in most of the images it is more subtle . while not a focus of this paper , the resulting astrometry is also affected : figure [ fig : alsalfpos ] shows the difference between the positions of psf stars in a k@xmath0 band image determined with the two methods . arrows are magnified by a factor of 2000 for clarity and the histogram of the offset of the positions is also shown . image . the arrows lengths are magnified by 2000 . _ bottom _ : histogram of the differences in position between the two methods.[fig : alsalfpos],scaledwidth=40.0% ] clearly , figure [ fig : alsalfpos ] indicates a problem using daophot in the multi - frame mode for gems images . we note that allframe uses a polynomial fit of maximum third order . it has been shown by @xcite that gems delivers a field of view with geometric distortions well described by a fifth order polynomial with an rms of about 0.01 px respect to the third order . for the exposure in figure [ fig : alsalfpos ] , we find a median difference in positions of 0.03 px between no constrains and the third order . however , the difference between polynomials could be more severe near the edges . by relying on the daophot transformations , we are potentially producing differences between the real position on the image of the stars and where the psf is fitted by allframe . by analyzing the test cmds for the two cases in the usual way ( figure [ fig : alsalfcmd ] ) , we do not find substantial differences around the msto between the two methods . however , to reduce astrometric systematic errors and eliminate residuals such as those in figure [ fig : alsalf ] , we use the single - frame method in the profile fitting . the instrumental magnitudes of stars measured in our data are calibrated to our reference catalog described in section [ sec : calibrationover ] by applying a zeropoint ( @xmath30 ) and a color correction ( @xmath31 ) . to determine these coefficients , we have matched our psf stars to the reference catalog obtaining more than 50 matches in every exposure / chip . we begin with an initial estimation of the zeropoint @xmath30 defined as the median of the difference between the instrumental and reference magnitude for all stars in our exposures that are matched to the reference catalog . zeropoints are worked out for each chip in each exposure , independently . the resulting values are shown in the left panel of figure [ fig : zerop ] . it is worthwhile to examine the distribution of values of the difference between the instrumental and reference magnitudes for matched stars in one of the chips / exposures , on which this initial estimate of the zeropoint is based . these values are shown in figure [ fig : seeingmagerr ] and are typical of all the chips / exposures . the range of values is very large , of the order of several magnitudes . while the median operation reduces the effect of outliers , the number of them is so large that it implies that there is an issue with the matched magnitudes . the origin of this issue is that we are comparing two catalogs with very different angular resolutions : our reference catalog is seeing - limited while our observations with gems are diffraction - limited . therefore , our reference stars include multiple stars that are resolved in our images but not in the reference catalog . this can be clearly seen in figure [ fig : seeingcalib ] , where the left image is from our reference dataset and the right image is the corresponding part of the image from our data . image . the large spread does not correlate with the magnitude errors estimated by daophot.[fig : seeingmagerr],scaledwidth=50.0% ] it is therefore necessary to reformulate our estimate of @xmath30 for each chip / exposure . for a star in our reference catalog , its true magnitude @xmath32 is related to its reported magnitude @xmath33 via @xmath34 , where @xmath35 is a correction that accounts for unresolved companions located within a distance equal to the spatial resolution of our reference catalog . normally , this would equal the seeing of the observation . however , given our reference catalog is based on a composite dataset , we determine its spatial resolution by making a histogram of the distances of every star to their closest neighbor in the catalog , shown in figure [ fig : seeingrad ] . the low cut - off to this distribution is at @xmath36 ( close to the median seeing value of 1.32 of the images that make this composite dataset ) . , scaledwidth=60.0% ] for a star @xmath37 with true magnitude @xmath38 that is present both in the reference and the gems catalog , we can identify all neighbors , that are found within a radius of 1.2 in our gemini data . further , we know the instrumental magnitudes @xmath39 of each of these neighboring stars . therefore , @xmath40 assuming small color corrections , @xmath41 , where the lowercase @xmath42 denotes instrumental magnitudes . figure [ fig : seeingmag ] plots @xmath35 against @xmath43 for all matched stars in a single chip / exposure . there is a clearly defined linear relationship between the reference magnitude and the instrumental magnitude corrected for the nearby neighbors that are unresolved in the reference catalog . accounting for this contribution naturally explains the large spread in the difference between instrumental and reference magnitudes that we observed in figure [ fig : seeingmagerr ] . the appropriate value for the zeropoint is then the y - intercept of the best fit linear model with a slope equal to 1 , shown by the dashed line in figure [ fig : seeingmag ] . we note that to determine the zeropoint to high accuracy as is done here requires us to eliminate all spurious detections in the vicinity of bright stars , especially those relating to the `` orphan '' halos discussed previously in section [ sec : psfrad ] . and the diffrence between the instrumental magnitudes @xmath42 in our data and the corresponding reference magnitudes @xmath33 in the seeing limited catalog ( see text for details ) . the best fit linear relationship with a slope of 1 is shown by the dashed line.[fig : seeingmag],scaledwidth=50.0% ] the k@xmath0 zeropoints calculated in this way are shown in the right panel of figure [ fig : zerop ] and are highly correlated between chips . the improvement of this calibration can be quantified by comparing the left and middle panels in figure [ fig : seeingcmd ] , where we have used the same metric of the width of the msto as used earlier . indeed , the improvement is also visible by eye in comparing the widths of the red giant branch . we do not find a significant spatial variation of the zeropoint in any of the images . we note that it is a common photometric calibration strategy to observe a standard star or stars near in time and space to the science observation . however , the variation in the zeropoint of each chip between subsequent exposures , that is visible in figure [ fig : zerop ] , warns against this strategy for mcao observations . adopting a zeropoint for a given image based on observations in a different image , even one taken immediately before in the same direction , could be a source of error for precision mcao photometric observations . there are many ways to simulate this ; we demonstrate this here by averaging the zeropoints in one band of each quadrant of gsaoi , and adopting these as the appropriate zeropoint corrections for all exposures . the result is a widening of the sequences in the cmd , as seen in the right panel of figure [ fig : seeingcmd ] . having estimated the zeropoints , we can now determine the color terms @xmath31 . we assume that these do not change as a function of exposure / time . we attempt to calculate only a single term @xmath31 for each chip and can therefore use all the exposures . to simplify our analysis , we consider only those matched stars that have little contamination from nearby stars ( @xmath44 ) , thus we can assume that the color reported in the reference catalog is close to the real one . for every of those stars , we calculate @xmath45 as a function of the color @xmath46 . where the star is measured in multiple exposures , we average these measurement and associate an error bar that is a combination of the reported magnitude error and the standard error in the mean . figure [ fig : colterm ] shows the results for each chip . for each chip , it is clear that the scatter is significant and it is unclear if there is a trend with color . to determine if there is a significant correlation for any of the chips , we perform a pearson correlation test . the pearson correlation coefficients of the k@xmath0 band are 0.34 , 0.27 , 0.23 , and 0.11 for the four chips , indicating that there is not a significant correlation with color . therefore , we assume the color terms are zero . all the stars found in each image are used to calculate the geometric transformation , weighted for their magnitude error . they are then matched to create the final catalog and the magnitude of each is determined from all its available calibrated measurements in each of the different exposures . these magnitudes are combined using the method of `` artificial skepticism '' @xcite . figure [ fig : cmds ] shows the final , fully calibrated and cleaned by photometric parameters and proper motions j vs ( v - j ) , k@xmath0 vs ( v - k@xmath0 ) , and k@xmath0 vs ( j - k@xmath0 ) cmds for ngc 1851 . the ( v - j ) and ( v - k@xmath0 ) cmds on the left have inset panels that show a zoom - in around the split subgiant branch where this feature is visible . the right panels show the same cmds with theoretical isochrones overlaid . the isochrones are generated with the dartmouth models of stellar evolution @xcite using @xmath47=-1.16 $ ] , @xmath48=0.4 $ ] @xcite . @xcite suggest the hypothesis that the cluster is composed of two discrete stellar populations , one of 11 gyr @xcite , the other 1 gyr older . as such , and for comparison purposes only , we show three different isochrones spanning this age range . these have been corrected for distance and reddening by @xmath49 @xmath50 @xmath51 where the extinction ratios @xmath52 , @xmath53 , @xmath54 are from @xcite and the visual distance modulus @xmath55 and the color excess @xmath56 are from @xcite . figure [ fig : pos ] shows the spatial positions of the stars in the final j - k@xmath0 cmd . holes correspond to regions of extreme crowding , as well as the positions of several very bright and saturated stars that prevent accurate photometry from being obtained for neighboring objects . cmd of figure [ fig : cmds].[fig : pos],scaledwidth=50.0% ] the overall depth of these data is impressive , reaching 23 and 22 magnitudes in j and k@xmath0 band , respectively , with formal uncertainties of 0.16 and 0.26 magnitudes . the knee of the main sequence @xcite is clearly visible in the nir - only cmd , some three magnitudes fainter than the msto . the extended horizontal branch is divided in two by the rr lyrae gap and , at around the same magnitude , we can observe the red giant bump on the red giant branch . we can also notice a weak population of blue stragglers . in all three cmds , the agreement between the theoretical isochrones and the actual stellar locus is quite remarkable considering the isochrones were derived solely on the preexisting relevant values in the literature and no effort has been made to match them to these new nir data . in each case , the isochrone appears to very nearly follow the central spine of the stellar locus , from the main sequence knee through the msto , through the ( split ) sub - giant branch , and up to the red giant branch . this gives us further confidence that the strategies that we have employed in our analysis , especially regarding the photometric calibration , are valid across the full magnitude and color range of the target stars . @xcite presented an earlier version of our k@xmath0 band photometry , in combination with the hst acs data , that was of sufficient quality to exhibit the double subgiant branch of this globular cluster . here again the split is present and we also see weak evidence for this feature in the j band data , when combined with the hst acs data . we do not see any evidence of the split subgiant branch in the nir - only cmd . the combined uncertainties on the j and k@xmath0 data would be too large for such structure . in this paper , we have presented a detailed analysis of the photometric performance of gems / gsaoi using data obtained during its science verification phase . in particular , we have focused on developing the optimal strategies for obtaining precise stellar photometry from mcao images using science based metrics to quantify the success or otherwise of our approaches for crowded fields . our strategy is based on the well known technique of psf fitting , specifically with the daophot ii suite of programs , but modified to account for the challenges posed by mcao data , especially the significant temporal and spatial variation in the psf . efficient exploitation of mcao imaging in the nir is absolutely essential to the future of ground - based astronomy given the development of the next generation of oir telescopes , especially tmt and the e - elt . the following is a list of our primary conclusions : * mcao delivers a more uniform correction than classical ao over the moderately wide field of view . however , the shape of the psf can still vary significantly in a complex manner , both spatially and temporally ( i.e. , between exposures ; section [ sec : performance ] ) , as also found by @xcite . it is possible that some of this variation has been removed since gems has undergone several realignments of the optics , but residual variability is still expected . as a consequence , this should be reflected in the creation of the psf model by allowing it to have a high degree of spatial variability , and by treating all exposures independantly . * the mcao correction is applied on a scale equal to the `` control radius '' of the system . the majority of the spatial variability of the psf is found within this radius . we demonstrate that we obtain the most precise photometry when the radius of the psf model is set approximately equal to the control radius of the ao system ( section [ sec : psfrad ] ) . if the psf radius is considerably smaller than the control radius , part of the variable psf controlled by the mcao system is not measured , causing a systematic error dependent on the position of the stars . if the psf radius is much larger than the control radius , then the resulting model attempts to include the halo of the psf . this region is generally not varying and contains a fixed fraction of the flux in the psf , and can therefore be accounted for during the calibration procedure . if the psf model includes these outer regions , then the low flux levels mean that other features , including noise artifacts and faint stars , are included and identified as intrinsic features of the psf . this results in an incorrect psf model for these regions and a reduction in the precision of the photometry . * there is an appreciable improvement in photometric precision when the psf model is based on a second iteration of the derivation procedure , i.e. , derived from an image which has had non - psf stars subtracted ( section [ sec : psfclean ] ) . this practice is likely less important with sparse fields . * during the profile fitting , the sky flux under every star is measured interior to the psf radius . in exposures with a large fwhm , we have noticed that using an area significantly smaller than the psf radius increases the precision of the photometry ( section [ sec : psfsky ] ) . we postulate that this is because a larger sky region is more likely to have contamination from unidentified stars , leading to inaccuracies in the sky measurements . * simultaneous profile fitting of all the observations , such as is done with allframe , should be avoided because of the difficulty in finding the proper geometric transformation for the edges of some of the images . treating the images independently leads to more robust photometric / astrometric solutions ( section [ sec : psfindep ] ) . * calibration of mcao photometry is complex . standard star observations are insufficient to estimate the zeropoint since the zeropoint changes for each exposure as a result of the mcao correction . it is therefore advisable to match every exposure and chip independently to a reference catalog of the same field , that is itself calibrated to the nir 2mass system . the measurement of the zeropoints must account for the different spatial resolutions of the catalogs ( section [ sec : calibration ] ) . for gems / gsaoi , we do not measure a significant color term . the procedures described in this paper have allowed us to derive extremely deep and precise nir photometry for the globular cluster ngc 1851 . comparison to isochrones suggest remarkable agreement between our observational data and the theoretical expectations for the color and magnitude distribution of the stars ( from the main sequence knee , through the main sequence turn - off to the subgiant and giant branch ) given our understanding of the age , metallicity , and distance of this cluster as derived from optical data . when combined with optical hst acs data , the ( v - j ) and ( v - k@xmath0 ) cmds allow for the identification of the split subgiant branch ( already demonstrated for the k@xmath0 band in @xcite . with precision photometry and high quality psf modeling in hand , a future contribution will discuss the astrometric performance and precision of our data using a similar approach of the identification of science - based metrics . mcao is a key technology for the future of ground - based nir astronomy , especially as we approach the era of tmt and e - elt , where the large apertures will provide diffraction limits that will significantly surpass even the james webb space telescope . gems / gsaoi allows us to explore the utility of this technology for science observations and develop solutions to the new challenges that are encountered . for example , nfiraos , the mcao system on tmt @xcite , is still expected to present noticeable psf variability even though it will be considerably more uniform and stable than gems . the instrument will be thermally controlled , on a nasmyth platform , and equipped with internal calibration tools . the geometry of the system will also improve the quality of the correction thanks to the use of more laser guide stars , a larger overlapping of the volumes probed by the guide stars , and a smaller scientific field of view . a comparable fraction of the flux will still reside outside the control radius compared to gems , since the density of actuators on the deformable mirrors will be similar . our current analysis suggests that the photometric calibration of tmt observations of crowded fields will be a significant challenge . our present technique of using a calibrated reference catalog of the field would require relatively deep , relatively high spatial resolution photometry if we are to identify large numbers of stars in common with ultra - deep , ultra - high resolution imaging from tmt . by exploring and solving these issues now , before the new generation of mcao instruments are on - sky , we can expect to improve significantly their science return at first light . based on observations for the program gs-2012b - sv-406 ( p.i . : mcconnachie ) at the gemini observatory , which is operated by the association of universities for research in astronomy , inc . , under a cooperative agreement with the nsf on behalf of the gemini partnership : the national science foundation ( united states ) , the national research council ( canada ) , conicyt ( chile ) , ministerio de ciencia , tecnologa e innovacin productiva ( argentina ) , and ministrio da cincia , tecnologia e inovao ( brazil ) . ascenso , j. , neichel , b. , silva , m. , fusco , t. & garcia , p. 2015 , ao4elt 4 conference proceedings , 31540 bec , m. , rigaut , f. j. , galvez , r. , et al . 2008 , , 7015 , 701568 blank , r. , anglin , s. , beletic , j. w. , et al . 2012 , , 8453 , 845310 bono , g. , stetson , p. b. , vandenberg , d. a. , et al . 2010 , , 708 , l74 boyer 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we present a detailed discussion of how to obtain precise stellar photometry in crowded fields using images obtained with multi - conjugate adaptive optics ( mcao ) , with the intent of informing the scientific development of this key technology for the extremely large telescopes . we use deep j and k@xmath0 exposures of ngc 1851 obtained using the gemini multi - conjugate adaptive optics system ( gems ) on gemini south to quantify the performance of the system and to develop an optimal strategy for extracting precise stellar photometry from the images using well - known psf - fitting techniques . we judge the success of the various techniques we employ by using science - based metrics , particularly the width of the main sequence turn - off region . we also compare the gems photometry with the exquisite hst data of the same target in the visible . we show that the psf produced by gems possesses significant spatial and temporal variability that must be accounted for during the photometric analysis by allowing the psf model a reasonably high degree of spatial variability and by treating all exposures independently . as with seeing - limited observations , steps need to be taken to minimize contamination of the psf model and sky estimates from unidentified faint neighboring stars . we show that standard star observations are insufficient to provide accurate photometric calibration of mcao data . instead , we cross - match sources in our mcao observations to a calibrated seeing - limited catalog with a shallower depth but sufficient to include a large number of common sources . however , done in this way , it is critical to consider the different spatial resolutions of the two datasets by accounting for stars that are multiple sources in the mcao dataset but which appear as single sources in the seeing - limited catalog . we identify photometric calibration as a critical issue for next generation mcao systems such as those on tmt and the e - elt . our final cmds reach k@xmath123 , below the main sequence knee of this cluster , and theoretical isochrones provide remarkable agreement with the stellar locus in our data from the main sequence knee to the red giant branch .

the blacklegged tick , ixodes scapularis ( northern populations previously treated as i. dammini ) , is the primary vector of the lyme disease bacterium , borrelia burgdorferi sensu lato ( s.l . ) east of the rocky mountains 1 . complex consists of at least 23 genospecies or genomospecies . in north america , at least 9 b. burgdorferi s.l . genospecies are present , namely b. americana , b. andersonii , b. bissettii , b. burgdorferi sensu stricto ( s.s . ) , b. californiensis , b. carolinensis , b. garinii , b. kurtenbachii , and b. mayonii 2 - 9 . of these 9 genospecies , b. andersonii , b. americana , b. bissettii , b. burgdorferi s.s . , b. garinii , and b. mayonii are known to be pathogenic to humans 9 - 12 . in nature , ( e.g. , a. phagocytophilum ) , borrelia miyamotoi ( relapsing fever group spirochete ) , an ehrlichia muris - like agent , and deer tick virus ( powassan virus group ) . of note , several tick - associated pathogens have been reported in i. scapularis collected from avian hosts , such as b. burgdorferi s.l . 13 , 14 , a. phagocytophilum 15 , b. microti 16 , and b. miyamotoi 17 . , b. microti , and a. phagocytophilum in an i. scapularis nymph collected from a veery , catharus fuscescens , a ground - frequenting neotropical songbird . in southwestern ontario , several small mammals that are reservoir - competent hosts of b. burgdorferi s.l . include : eastern chipmunks , tamias striatus 19 , 20 ; white - footed mice , peromyscus leucopus 21 ; deer mice , peromyscus maniculatus 22 , 23 ; northern short - tailed shrews , blarina brevicauda 24 , 25 ; and meadow vole , microtus pennsylvanicus 26 . although white - tailed deer , odocoileus virginianus , are hosts of i. scapularis and support i. scapularis reproduction , they are not competent reservoir hosts of b. burgdorferi 27 . migratory songbirds widely disperse larval and nymphal i. scapularis ticks across central and eastern canada during spring migration 13,14 , 28 - 30 . neotropical and southern - temperate passerines transport i. scapularis as far north as northern alberta 28 and , likewise , carry lyme disease vector ticks during trans - border migration to as far north as southern yukon 13 . when passerine migrants make landfall at established populations of i. scapularis , they can be parasitized by questing i. scapularis larvae and nymphs . peak questing activity for i. scapularis nymphs coincides with peak northward spring migration 31 , 32 . subsequently , northbound migrants could transport i. scapularis immatures from central , southern , northeastern , and mid - atlantic states and , likewise from established populations in southwestern ontario , including long point , turkey point and wainfleet marsh , and then release them in the dundas area . although there are currently no bird banding stations operating in the hamilton - wentworth region , there are stations to the south and to the north that provide substantive data on songbird - transported i. scapularis immatures 30 . 33 provided the first record of a b. burgdorferi s.l .- infected i. scapularis in the hamilton metropolitan area , which encompasses dundas ; it was collected from an untraveled dog in 1997 . in addition , a 10-year , tick - host study ( 1993 - 2002 ) , which was conducted across ontario , reported b. burgdorferi s.l .- infected i. scapularis adults in the hamilton - wentworth area 34 . these tick researchers found that all i. scapularis , which were submitted from dogs , cats , horses , and people , were adults ; no larvae or nymphs of this tick species were presented . however , the same study reported larvae and nymphs of several other tick species on mammalian hosts . because residents in the dundas area were being bitten by ticks and contracting lyme disease , we wanted to determine the prevalence of b. burgdorferi s.l . in i. scapularis ticks in the dundas area , and ascertain whether these ticks are a public health risk . a 2-year study was conducted in the vicinity of dundas , ontario ( 43.2643 n , 79.9533 w ) , and encompassed a well - drained , hilly block of land situated at the west end of lake ontario in the hamilton - wentworth region , which is situated on the cusp of the niagara escarpment . this 56 km area consists of deciduous forests that are interspersed with residential areas , and bordered by highway 99 , highway 52 , highway 5 , and rock chapel road . the predominate tree species in this locality are : sugar maple , acer saccharum ; red maple , acer rubrum ; red oak , quercus rubra ; white oak , quercus alba ; white ash , fraxinus americana ; and black cherry , prunus serotina . the dundas area supports a wide array of wildlife mammals that are common in deciduous forests in northeastern north america . mid - sized mammals include gray squirrels , sciurus carolinesis ; red squirrels , tamiasciurus hudsonicus ; eastern cottontail rabbits , sylvilagus floridanus ; raccoons , procyon lotor ; and striped skunk , mephitis mephitis . small mammals include deer mice ; white - footed mice ; meadow vole ; northern short - tailed shrew ; eastern chipmunk ; and house mouse , mus musculus . not only do i. scapularis adults parasitize white - tailed deer , they also parasitize eastern cottontails , raccoons , and striped skunks 35 . we asked local veterinarians and pet groomers to participate in our study because dogs and cats are good sentinels of ixodid ticks . we prepared and distributed a chart showing adults of four species of ticks , which are commonly found in the area , and asked local veterinarians and pet groomers to submit three of the four illustrated species . each participant was given ' tick - host information ' sheets , and asked to complete and submit one with each tick specimen . the background information included : host , location / residency of companion animal , travel history , date collected , and collector . we discouraged submissions of american dog ticks , dermacentor variabilis , which are not a vector of b. burgdorferi s.l . we emphasized that i. scapularis ticks were the focus of our study , but invited other tick species . in addition , a local volunteer flagged 2 ha of forests and ecotones ( woods edge ) ; these are areas where i. scapularis are most commonly found . flagging was timed to correspond with the bimodal questing activity periods at this lattitude of i. scapularis adults in the spring and fall . the flagging cloth was made of flannel - back vinyl ( 88 70 cm ) , and the length of the pole was 229 cm . collection permits were not required because ticks are blood - sucking ectoparasites , and there are no proprietary issues with these arthropod pests . the i. scapularis adults which attached to the flag , were removed with fine - pointed , stainless steel tweezers and placed in round - bottom , 8.5 ml polypropylene tubes ( 15.7 x 75 mm ) with labels consisting of background information . a 7-mm hole was drilled in the polyethylene push caps ( 15.7 mm diameter ) for ventilation and , to prevent ticks from escaping , tulle netting was placed over the mouth of the vial before the push cap was inserted . the capped vials were then placed in self - sealing , double - zipper , plastic bags with a slightly moistened paper towel . ticks were sent directly by express mail to the tick identification laboratory ( jds ) for examination and recording . the first portion of ticks were sent by courier to the culturing and pcr amplification laboratory ( jfa ) . the dna detection methods have been previously described 38 - 40 . during the second phase of our study , i. scapularis ticks were put in 2 ml micro tubes containing 94% ethyl alcohol , and sent by courier to a separate laboratory ( klc ) . dna extraction . dna was extracted from the ethanol - preserved ticks using a salting out procedure similar to that described previously 10 . each tick was cut into several pieces with a sterile scalpel blade within a 2-ml microtube . then , 500 l 1x tissue and cell lysis buffer ( masterpure , epicentre , madison , wi ) and 200 g of proteinase k were added . after the sample was heated in a water bath at 65c for 1 hour , the liquid was transferred to a clean tube , and then chilled at -20c for 5 min . then , 200 l of 7.5 m ammonium acetate was added , and the tube was vortexed on high speed for 30 sec . the sample was then chilled at -20c for 5 min again , centrifuged at 16,000 rcf for 5 min at room temperature in a tabletop centrifuge ( eppendorf model 5424 ) to pellet protein , and the supernatant was transferred to a clean tube . to enhance dna precipitation , 3 l of polyacryl carrier ( mrc , cincinnati , oh ) was added , and mixed by vortexing for 15 sec , followed by the addition of 700 l of 100% isopropanol . each tube was inverted 50 times to gently mix , and then chilled overnight at -20c . supernatant was discarded , and the pellet was washed twice with 1 ml of 75% ethanol , by inverting and rotating the tube gently 5 times to rinse the pellet , and inside of the tube , and then centrifuging for 5 min at 16,000 rcf for each rinse . the residual ethanol was removed , and the pellet was air dried at room temperature for 10 min . to rehydrate , 100 l tris - edta buffer ( ph 8.0 ) was added , and the tube was heated at 65c for 5 min . thereafter , each sample was stored at 0 - 4c . tick extracts were initially screened for b. burgdorferi s.l . by two nested ( hemi - nested ) pcr assays designed to amplify separate portions of the 41-kda chromosomal flagellin ( flab ) gene . primary / outer reaction primers for pcr1 were 313f ( 5'-gca - gac - aga - ggt - tct - ata - caa - att - g-3 ' ) and 551r ( 5'-gct - tca - tct - tgg - ktt - gct - cca - aca - t-3 ' ) , which amplify a 238-bp fragment ; inner reaction primers were 313f and 506r ( 5'-gct - tga - gay - cct - gaa - agt - gat - gct - gg ) , which amplify a 194-bp product . primers for pcr2 were 481f ( 5'-cca - gca - tca - ctt - tca - ggr - tct - ca-3 ' ) and 737r ( 5'-gca - tca - act - gtr - gtt - gta - aca - tta - aca - gg-3 ' , which amplify a 257-bp product , followed by 532f ( 5'-gga - gca - amc - caa - gat - gaa - gct - att - gc-3 ' ) and 737r , amplifying a 206-bp product . positive results with pcr1 and pcr2 were confirmed with additional b. burgdorferi s.l . specific primers for the 5s-23s rrna intergenic spacer and flab gene as described previously 41 , 42 , as well as borrelia species primers for the 16s-23s rrna intergenic spacer 43 . first round pcr amplifications contained 2.5 l of tick dna extract in a total reaction volume of 50 l . first round amplifications utilized a hot start pcr master mix ( hotmastermix , 5 prime , gaithersburg , md ) resulting in a final concentration of 1.0 u of taq dna polymerase , 45 mm kcl , 2.5 mm mg2 + , 200 m of each deoxynucleoside triphosphate , and 0.5 m of each primer . second round amplifications used gotaqgreen pcr master mix ( promega , madison , wi ) , which allowed samples to be directly loaded into agarose gels without the addition of a gel loading buffer . all pcrs were carried out in an applied biosystems ab2720 thermal cycler ( life technologies , thermofisher scientific , waltham , ma ) . each primary pcr consisted of initial denaturation at 94c for 2 min , followed by 35 cycles at 94c for 30 sec , primer annealing at 5c below the lowest primer 's calculated melting temperature for 30 sec , and extension at 65c for 1 min , with a final extension at 65c for 5 min . nested reactions included initial denaturation at 94c for 1 min , followed by 35 cycles of amplification with an annealing temperature of 55c , and extension temperature of 72c . pcrs were set up in an area separate from dna extractions , and within a pcr clean cabinet ( cleanspot workstation , coy laboratory products , grass lake , mi ) equipped with a germicidal uv lamp . other precautions to prevent carryover contamination of amplified dna included different sets of pipettes dedicated for dna extraction , pcr setup , and post - amplification activities , the use of aerosol barrier filter pipette tips , and soaking pipettes used for handling dna samples in 10% bleach solution after setup of each pcr . as a further measure to prevent dna artifact contamination of pcr testing , no positive control samples were used . pcr products were electrophoresed in 2% agarose gels , which were stained with ethidium bromide , and visualized and recorded with a digital gel documentation unit . pcr products from pcr1 and pcr2 positive samples were purified using the wizard sv gel and pcr clean - up system ( promega , madison , wi ) . dna templates were sequenced 44 using both the forward and reverse primers used in the nested pcrs . investigator - derived sequences were compared with those obtained by searching the genbank database ( national center for biotechnology information ) using the basic local alignment search tool ( blast ) 45 , and aligned using clustal x 46 . of note , dna sequencing was not conducted during phase 1 ; it was only available in phase 2 . nucleotide sequences . in order to confirm the identity of b. burgdorferi s.l . in the dundas area , we obtained and sequenced borrelial amplicons from two i. scapularis females ( 14 - 5a183 , 14 - 5a184 ) that were collected in phase 2 . dna sequences for amplicons of flab gene from pcr1 ( base position 313 to 506 ) for both ticks , as well as the sequence for pcr2 ( base position 532 to 737 ) for tick 14 - 5a184 , were deposited in the genbank database under the accession numbers kx011445 , kt764114 , and kt764115 . based on pcr amplification , 12 ( 41% ) of 29 i. scapularis adults , which were collected in the dundas area , were positive for b. burgdorferi s.l . amplicons , which were obtained from two i. scapularis females ( 14 - 5a183 , 14 - 5a184 ) , we determined that they both belonged to b. burgdorferi s.s . , which is pathogenic to humans and certain domestic animals . multiple parasitisms were experienced by 4 hosts ( 2 cats , 1 dog , 1 human ) . two i. scapularis adults were collected in the spring , while three i. scapularis adults were collected in the fall . additionally , we collected 3 other ticks species in the dundas area : amblyomma americanum ( lone star tick ) , d. variabilis ( american dog tick ) , and ixodes cookei ( groundhog tick ) from dogs , cats , and humans . , they are all known to carry multiple tick - borne pathogens , which can cause associated pathologies in humans . while flagging , we observed that d. variabilis and i. scapularis are sympatric in the dundas area . some of these infected ticks are likely introduced by migratory songbirds during northbound spring migration . importantly , these b. burgdorferi s.l .- infected i. scapularis ticks pose a public health risk to outdoors people and companion animals . recent studies show prevalence rates of b. burgdorferi s.l . in i. scapularis adults collected in the upper midwest and the northeastern united states ranging from 27 - 47% 47 , 48 . interestingly , it is analogous to the 35% infection prevalence in i. scapularis nymphs collected from migratory songbirds in eastern and central canada 30 . when these engorged nymphs molt to adults , they retain the same level of b. burgdorferi s.l . since no nymphs were collected in our study , we suggest that i. scapularis females are the most likely life stage to bite humans , and present the greatest risk for b. burgdorferi s.l . infection in this bioregion . based on earlier bird - tick studies , migratory songbirds transport i. scapularis immatures into southwestern ontario during spring migration 13 , 14 , 28 - 30 . after feeding to repletion , engorged ticks detach from ground - frequenting songbirds at stopovers , and descend into the cool , moist leaf litter . within 5 - 8 weeks , these ticks molt to the next life stage , and conduct host - seeking activities . in the dundas area , i. scapularis adults start questing for hosts in october and , if they are unsuccessful in parasitizing a suitable host , will overwinter and quest for a host in the spring . because transstadial transmission of b. burgdorferi s.l . is apparent in i. scapularis , adults have an equivalent infection prevalence to that of replete nymphs . since 35% of songbird - transported i. scapularis nymphs are infected with b. burgdorferi s.l . 30 , and 41% of the i. scapularis adults in our study were infected , we suggest that migratory songbirds have a supportive role in supplying i. scapularis immatures to the dundas area . in addition , larval and nymphal a. americanum ticks are transported into the dundas area by migratory songbirds during cross - border spring migration 13 . after these bird - transported ticks have fed to repletion , they detach from their hosts and , likewise , descend into the leaf litter to molt to the next development life stage in 6 - 8 weeks . by august , unfed lone star ticks are ready to conduct host - seeking activities , and parasitize people and domestic animals , such as dogs , cats , and people . long - distance migrants can transport bird - feeding ticks hundreds of kilometres during northward spring migration from as far south as the southern united states , the caribbean , and central and south america , and disperse them widely across southern canada 13 , 14 , 28 - 30 , 49 - 54 . not only do songbirds provide an influx of i. scapularis , they contribute to the establishment of blacklegged tick populations 50 , 55 , and support the enzootic maintenance of b. burgdorferi s.l . in these populations since songbirds widely disperse lyme disease vector ticks , people do not have to visit an endemic area to contract lyme disease . the high prevalence of deer can greatly influence high numbers of i. scapularis in tick habitats . during a deer count in the dundas area in 2009 , wildlife researchers documented 0.35 deer / ha , which is 4 times the number considered ecologically desirable 56 and , in 2013 , they reported 0.3 deer / ha , again , triple the ideal number . in 2009 , the highest concentration in urban areas was 1.54 deer / ha . because deer are hosts of male and female i. scapularis , these cervids facilitate and promote the development and maintenance of i. scapularis populations . in addition , these high deer counts signify the potential to promote all 4 motile life stages of i. scapularis . such an overpopulation of white - tailed deer exacerbates the abundance of i. scapularis in the dundas area . in this study , the highest concentration of i. scapularis occurred in parkland areas , namely christie lake conservation area , crooks hollow , and borer 's falls ( figure 1 ) . these no - hunt areas provide sanctuary for white - tailed deer , especially during the fall hunting season . these woodland parks have a variety of acorn - bearing oak trees , especially red oak , which are a nutritious source of food for deer . not only do acorns act as an energy reserve for deer , they act as a nutritious source of food for small rodents ( i.e. , white - footed mice , deer mice , eastern chipmunks ) 57 . a bumper crop of acorns sparks a mouse boom the following year and helps to support and maintain i. scapularis 58 . mast production provides one of the key components to bring i. scapularis and vertebrate hosts together to promote enzootic lyme disease transmission . in essence , parkland areas in the dundas area have natural biotic and climatic attributes that support i. scapularis and reservoir - competent hosts . when there is a bumper acorn crop , white - tailed deer will move from maple - dominated areas to oak - dominated areas 59 . acorns are rich in protein and fats , and are a favorite energy source for deer and mice . the acorn - laden canopy area , at the base of the oak trees , becomes a focal hub for deer and mice . with the abundant food supply , mice increase in numbers and , in the following year , act as preferential hosts for questing i. scapularis larvae . stafford 59 revealed that i. scapularis larvae move up to 2 m from the egg laying site , and carroll 60 found i. scapularis larvae at a height of 2 m on the trunks of oaks . these findings indicate that gravid female ticks often drop close to the trunks of oaks 59 , 60 . although it would be next to impossible to see or track the drop of replete i. scapularis females , questing larvae are commonly found on well - drained soils either at field - forest ecotones ( woods edge ) where deer pasture and bed - down or in wooded areas , especially at the base of oak trees 61 . based on odoriferous vapors ( i.e. , ammonia from small mammal droppings , composting oak leaves ) , replete females lay eggs in this nut - producing area that provides an ideal microhabitat 61 , 62 . with the combination of deer and other mammalian hosts , this community of hosts , our data revealed that i. scapularis females may be the primary source of spirochetal infection in the dundas area . we recorded four occurrences where more than one i. scapularis parasitized the same host . in one case , three i. scapularis ticks were individually removed from a cat on two separate occasions ; two ticks were collected on one day and one of these ticks was positive for b. burgdorferi s.l . as well , two i. scapularis females were removed from a dog on the same day . additionally , two i. scapularis females were removed from a human on the same day ; one of these ticks was positive for b. burgdorferi s.l . collectively , these co - infestations of i. scapularis females provide supportive evidence that i. scapularis may be established in the dundas valley . this study provides new information regarding lyme disease vector ticks in the dundas area . over a 5-yr period ( 2009 - 2013 ) , the local health unit ( hamilton public health services ) reported no occurrence of locally - acquired , b. burgdorferi s.l .- infected blacklegged ticks in their service area ( 1117 km ) 62 , 63 . in comparison positive i. scapularis during a 2-yr period in the dundas sample area ( 56 km ) , which is 20 times smaller in size . this sharp contrast reveals a significant difference in the actual prevalence of b. burgdorferi s.l .- infected i. scapularis in the hamilton - wentworth area . in essence , our study shows that dogs and cats , which roam outdoors , are better sentinels in representing the occurrence of i. scapularis . underreporting of i. scapularis can easily occur because people are not expecting ticks in the early spring and late fall when they have bimodal questing activity . furthermore , i. scapularis anesthetize the skin when they bite , and people are unlikely to be aware of a feeding tick . moreover , i. scapularis larvae and nymphs are very tiny , and can be easily overlooked as they take a blood meal . whenever a surveillance team is trying to determine whether i. scapularis ticks are present in an area , dogs and cats can provide a reliable gauge of tick activity . deer management strategies need to be implemented to limit the number of deer in the dundas area . during the hunting season , deer congregate in no - hunt parklands and , naturally , increase the mating potential of i. scapularis males and females and , thus , produce a new generation of ticks . since b. burgdorferi s.l .- infected i. scapularis were collected at several locations in the dundas area , signs need to be erected in no - hunt parkland areas to warn the public of questing ticks infected with b. burgdorferi s.l . according to the ontario health protection and promotion act , the medical officer of health is legally responsible to erect warning signs where any area contains a reportable disease or communicable disease that poses a public health hazard . our findings reveal that , in the dundas area , i. scapularis harbor b. burgdorferi s.s . which is pathogenic to humans . anyone bitten by an i. scapularis tick should have it tested for b. burgdorferi s.l . and other tick - transmitted pathogens ; when a b. burgdorferi s.l .- infected i. scapularis takes a blood meal , it typically transmits spirochetes that migrate outward from the bite site . in vivo , b. burgdorferi s.l . has diverse forms ( i.e. , spirochetes , blebs , granules , round bodies , atypical forms ) 64 and , collectively , form biofilms 65 . spirochetes are able to evade the immune system , and will attach to , invade , and kill human b and t lymphocytes 66 . as spirochetes disseminate in the body , a myriad of clinical manifestations commonly unfold , including fatigue , headaches , low - grade fever , stiff neck / back , disturbed sleep , memory and sensory loss . this febrile illness can affect several body systems : cardiac , endocrine , gastrointestinal , musculoskeletal , neurological , otological , and ophthalmic 67 . neurological deficits are common in both children and adults . as spirochetes attack nerves and ligamentous tissue , they produce neurotoxins that cause an inflammatory response in the surrounding tissue 68 , 69 . as spirochetemia progresses in the central nervous system , demyelination and apoptosis in addition , as this tick - borne zoonosis advances , it induces inflammatory cytokines , such as interleukin 1 , interleukin 6 , and tnf - alpha , and produces mitochondrial dysfunction , oxidative stress , physical and hormonal abnormalities and , ultimately , profound fatigue 69 , 70 . left untreated or inadequately treated , b. burgdorferi s.l . will sequester in deep - seated tissues , such as bone 71 , brain 72 - 74 , eye 75 , muscle 76 , collagenous tissues ( ligaments , tendons ) 77 , 78 , glial and neuronal cells 79 , 80 , and fibroblast / scar tissue 81 . in some cases . can be persistent , lyme disease spirochetes have been detected in and cultured from tissues and body fluids after conventional , short - term antibiotic treatment in animals , including humans 83 - 87 . we document that 41% of i. scapularis adults in the dundas area were infected with lyme disease spirochetes , and confirm that b. burgdorferi s.s . , which pathogenic to humans , is present in the hamilton - wentworth region . advocacy and surveillance programs conducted by the local public health unit fail to reflect and authenticate the presence of b. burgdorferi s.l . in locally - acquired i. scapularis , and give the false impression that there is no lyme disease in the hamilton - wentworth area . the number of white - tailed deer needs to be significantly reduced to minimize the public health risk of lyme disease . signs need to be erected to warn hikers that b. burgdorferi s.l .- infected i. scapularis are present in the parkland areas . this high risk area presents a health - care challenge for people bitten by i. scapularis . veterinarians , clinicians , medical professionals , public health officials , and the populace must be aware that lyme disease can be contracted in the dundas area and surrounding hamilton - wentworth region .

lyme disease has emerged as a major health concern in canada , where the etiological agent , borrelia burgdorferi sensu lato ( s.l . ) , a spirochetal bacterium , is typically spread by the bite of certain ticks . this study explores the presence of b. burgdorferi s.l . in blacklegged ticks , ixodes scapularis , collected at dundas , ontario ( a locality within the region of hamilton - wentworth ) . using passive surveillance , veterinarians and pet groomers were asked to collect blacklegged ticks from dogs and cats with no history of travel . additionally , i. scapularis specimens were submitted from local residents and collected by flagging . overall , 12 ( 41% ) of 29 blacklegged ticks were infected with b. burgdorferi s.l . using polymerase chain reaction ( pcr ) and dna sequencing , two borrelial amplicons were characterized as b. burgdorferi sensu stricto ( s.s . ) , a genospecies pathogenic to humans and certain domestic animals . notably , three different vertebrate hosts each had two engorged i. scapularis females removed on the same day and , likewise , one cat had three repeat occurrences of this tick species . these multiple infestations suggest that a population of i. scapularis may be established in this area . the local public health unit has been underreporting the presence of b. burgdorferi s.l .- infected i. scapularis in the area encompassing dundas . our findings raise concerns about the need to erect tick warning signs in parkland areas . veterinarians , medical professionals , public health officials , and the general public must be vigilant that lyme disease - carrying blacklegged ticks pose a public health risk in the dundas area and the surrounding hamilton - wentworth region .

majorana quasi - particles ( qps ) and majorana fermions have attracted much attention in the wide research field , ranging from high energy physics to low temperature physics of ultracold atomic gases , @xcite and for the application to topological quantum computations . @xcite the majorana qp and majorana fermionic operator are defined by @xmath2 and @xmath3 , respectively , which imply that the particle and antiparticle are identical . it has been proposed that the majorana nature brings new physics , such as non - abelian statistics of vortices in chiral superfluids @xcite and ising - like spin dynamics for time - reversal invariant superfluids . @xcite the majorana nature itself is an intriguing subject to further studies . candidate systems that exhibit the majorana nature are quite rare , e.g. , spin - triplet superconductors or superfluids , @xmath4-wave feshbach resonated superfluids , @xcite fractional quantum hall systems with the 5/2 filling , @xcite interfaces between a topological insulator and an @xmath5-wave superconductor , @xcite and @xmath5-wave superfluids with particular spin - orbit interactions . @xcite spin - triplet superconductors or superfluids satisfy the following bogoliubov - de gennes equation with the wave function @xmath6 and the energy @xmath7 : @xmath8 the eigenstates yield one - to - one mapping between the positive energy states @xmath9 and the negative energy states @xmath10 owing to the symmetry @xmath11 , where @xmath12 is the pauli matrix in the particle - hole space . the symmetry of the wave function leads to the relation of the bogoliubov qp operator @xmath13 . therefore , the bogoliubov qp with zero - energy is the majorana qp , @xmath14 . zero - energy bound states of the qps appear whenever the underlying potential for the qps changes its sign . the situation appears at edges , surfaces , or vortices with odd integer winding numbers , where the qps have zero - energy andreev bound states . for the edge or surface , the majorana fermion surface state @xmath3 exists as well as @xmath14 . @xcite among known possible spin - triplet superconductors @xcite upt@xmath15 , uge@xmath16 , and urhge , sr@xmath16ruo@xmath17 is a prime candidate of chiral spin - triplet superconductors . the precise pairing symmetry , however , has not yet been identified and has been under strong discussion . a @xmath18 scenario is reexamined from various aspects . @xcite obviously , we want to experiment with more candidate materials for observing the majorana nature . the superfluid @xmath0he consists of spin - triplet cooper pairs . @xcite for the @xmath0he there is a huge amount of experimental data by intensive researches for long years . @xcite there are two stable phases , abm- ( a- ) and bw- ( b- ) phases , for the superfluid @xmath0he in a bulk without a magnetic field . the a - phase is stabilized in narrow regions at high temperatures and high pressures while the b - phase is stabilized in other wide regions within the superfluid phase . the order parameter ( op ) of the a - phase has point nodes toward @xmath1-vector , which signifies the direction of the orbital angular momentum , or orbital chirality , whereas the b - phase has a full gap . the majorana natures for the a- and b - phases differ due to the topology of the gap on the fermi surface . @xcite time reversal symmetry is also different for the a- and b - phases . since up - up and down - down spin cooper pairs have the same chirality for the a - phase , the time - reversal symmetry is broken and net mass current flows along the boundary or the edge . in contrast , since up - up and down - down spin cooper pairs have the opposite chirality , the b - phase is a time - reversal invariant . instead of the mass current canceled by up - up and down - down spin cooper pairs , the spin current flows . the difference of time reversal symmetry between the a- and b - phases is analogous to the difference between the quantum hall state and the quantum spin hall state . @xcite our aim is to propose a concrete experimental design to detect the majorana nature based on quantitative calculations and understand systematically how to observe the majorana nature in the superfluid @xmath0he a- and b - phases . the quantitative calculations are performed by quasi - classical theory which yields information of qps . the quasi - classical theory is valid when @xmath19 , where @xmath20 is superfluid gap and @xmath21 is the fermi energy . since @xmath22 , the theory is appropriate for the superfluid @xmath0he . @xcite the quasi - classical framework is well established within the weak - coupling limit . the superfluid @xmath0he at the lower pressure can be described within the weak - coupling scheme @xcite without delicate strong - coupling corrections . in the slab geometry , both the a- and b - phases are stabilized by changing thickness and temperature even at zero pressure . @xcite therefore , we can deal with the a- and b - phases by the quasi - classical theory within the weak - coupling limit . here , we introduce several systems of the slab geometry . by bennett _ et al . _ , @xcite the superfluid @xmath0he is confined in a thin slab box with a thickness @xmath23 @xmath24 m and an area of the base 10 mm @xmath25 7 mm . the thickness is of the order of @xmath26 at @xmath27 , where @xmath28 is the coherence length at @xmath29 . at issp , university of tokyo , @xcite sample disks with a thickness @xmath30 @xmath24 m , which is of the order of the dipole coherence length , and a diameter 3 mm are used . the issp group can rotate the sample disks with the highest speed in the world and investigates half - quantum vortices . at riken , @xcite the inter - digitated capacitors are used for making a film of the superfluid @xmath0he . the group can control thicknesses of the film from 0.3 to 4 @xmath24 m . under those experimental situations , we consider the surface states from not only the upper and lower surfaces in a slab but also the side edges including the corners and evaluate the dependence of the majorana state on the thickness of a slab . by the quasi - classical calculation , we show thedirac valley " ( fig . [ 3d](a ) ) for the a - phase at the side edges . in a thick slab , we consider the @xmath31-component of the op , which was neglected in the previous work @xcite since @xmath1-vector was assumed to be perpendicular to the thin slab . several groups have demonstrated that the majorana fermion surface state has the dispersion of @xmath32 with the surface perpendicular to the @xmath33-axis in the b - phase , where @xmath34 is the fermi wave number and @xmath35 . @xcite this implies that the surface state consists of a single majorana cone . we show the majorana cone ( fig . [ 3d](b ) ) by the quasi - classical calculation for a thick slab and investigate the variation of the dispersion by the thickness of a slab ( fig . [ 3d](c ) ) . the zero - energy state at the corner is also discussed . at the left side edge l " and the right side edge r " . ( b ) majorana cone for the b - phase in a thick slab @xmath36 at the upper or lower surface . ( c ) split majorana cone for the b - phase in a thin slab @xmath37 at the upper or lower surface . the units of energy and wave length are @xmath38 and @xmath34 , respectively . , width=321 ] the arrangement of this paper is as follows : in sec . [ sec : theory ] , we formulate the quasi - classical theory based on the quasi - classical green s function which gives quantitative information of qps . we explain numerical methods in sec . [ sec : sys ] , which is supplemented by the symmetry considerations of the quasi - classical green s function given in appendix . in secs . [ sec : a ] and [ sec : b ] for the a- and b - phases , we show results of the spatial structures of the op , the current distribution , and the local density of states ( ldos ) for qps which relates to the majorana modes . in sec . [ sec : discuss ] , we discuss difference of the majorana zero modes in the a- and b - phase and propose several experimental designs to observe the majorana nature . in addition , we discuss the majorana zero mode in the stripe phase . the final section is devoted to a summary . we start with the quasi - classical spinful eilenberger equation , @xcite which has been used for studies of the superfluid @xmath0he . @xcite the low energy excitation modes at the surface are discretized in the order of @xmath39 , @xcite where @xmath40 is a length of the system . if @xmath40 is a macroscopic length , which is much larger than @xmath41 , the low energy excitation modes at the surface can be regarded as continuous spectra . because there is the exact zero - energy excitation at the surface of the superfluid @xmath0he a - phase @xcite and b - phase , @xcite the quasi - classical theory can be used to discuss the majorana qp . the quasi - classical green s function @xmath42 is calculated using the eilenberger equation @xmath43 , \label{eilenberger eq}\end{gathered}\ ] ] where the ordinary hat " indicates the 2 @xmath25 2 matrix in spin space and the wide hat " indicates the 4 @xmath25 4 matrix in particle - hole and spin spaces . the quasi - classical green s function is described in particle - hole space by @xmath44 with the direction of the relative momentum of a cooper pair @xmath45 , the center - of - mass coordinate of a cooper pair @xmath46 , and the matsubara frequency @xmath47 . the quasi - classical green s function satisfies a normalization condition @xmath48 . the fermi velocity is given as @xmath49 on the three dimensional fermi sphere . we solve eq . by the riccati method . @xcite we introduce riccati amplitude @xmath50 and @xmath51 related to particle- and hole - like projections of the off - diagonal propagators , respectively . equation can be rewritten as riccati equations @xmath52 @xmath53 the equations are solved by integration toward @xmath45 for @xmath54 and toward @xmath55 for @xmath56 . from the riccati amplitude , the quasi - classical green s function is given as @xmath57 the self - consistent condition for the pair potential @xmath58 is given as @xmath59 where @xmath60 is the density of states in the normal state , @xmath61 is a cutoff energy setting @xmath62 with the transition temperature @xmath63 in a bulk , and @xmath64 indicates the fermi surface average . the pairing interaction @xmath65 for cooper pairs with an orbital angular momentum @xmath66 , where @xmath67 is a coupling constant . in our calculation , we use a relation @xmath68 spin - triplet op is defined by a vectorial notation @xmath69 with the pauli matrix @xmath70 in spin space . the complex vector @xmath71 is perpendicular to the spin @xmath72 of a cooper pair , namely , @xmath73 . the @xmath71 can be expanded in orbital momentum directions , @xmath74 where @xmath75 is a complex 3 @xmath25 3 matrix with a spin index @xmath24 and an orbital index @xmath76 . the repeated index implies summation over @xmath77 , @xmath78 , and @xmath33 . this paper is discussed for the chiral state in the a - phase , polar state , b - phase , and planar state . symbolic descriptions of the op in their state are the following : for the chiral state , @xmath79 for the polar state , @xmath80 for the b - phase , @xmath81 and for the planar state , @xmath82 where @xmath83-vector is perpendicular to the spin of a cooper pair . @xmath83-vector and the momentum direction are permitted to rotate spherically in the spin and momentum space , respectively . by using the self - consistent quasi - classical green s function , the mass and spin currents are calculated by @xmath84 \rangle_{{\ensuremath{\boldsymbol{k } } } } , \label{mass current}\\ { \ensuremath{\boldsymbol{j}}}_s^{\mu } ( { \ensuremath{\boldsymbol{r } } } ) & = \frac{\hbar } { 2}n_0\pi k_bt\sum_{-\omega_c \le \omega_n \le \omega_c } \langle { \ensuremath{\boldsymbol{v}}}({\ensuremath{\boldsymbol{k } } } ) \ { \rm i m } \left [ g_{\mu } ( { \ensuremath{\boldsymbol{k}}},{\ensuremath{\boldsymbol{r } } } , \omega_n ) \right ] \rangle_{{\ensuremath{\boldsymbol{k } } } } , \label{spin current}\end{aligned}\ ] ] respectively , where @xmath85 is the mass of the @xmath0he atom and @xmath86 is a component of the quasi - classical green s function @xmath87 in spin space , namely , @xmath88 ldos for energy @xmath89 is given by @xmath90 \right\rangle_{{\ensuremath{\boldsymbol{k}}}},\end{aligned}\ ] ] where @xmath91 is a positive infinitesimal constant and @xmath92 is angle - resolved ldos . typically , we choose @xmath93 . for obtaining @xmath94 , we solve eqs . with @xmath95 instead of @xmath96 under the pair potential obtained self - consistently . we consider a cross - section a of a slab with a thickness of @xmath97 along the @xmath33-direction and a macroscopic length of @xmath40 along the @xmath77-direction , shown in fig . [ system](a ) . it is assumed that the quasi - classical green s function and op are homogeneous along the @xmath78-direction . we also assume that the surfaces of the slab are specular , where specularity is controlled by coating the surface with @xmath98he atoms . @xcite under the boundary condition , the quasi - classical green s function or the riccati amplitude changes only the direction of the relative momentum by mirror reflection at a surface @xmath99 , namely , @xmath100 or @xmath101 and @xmath102 , where @xmath103 with a unit vector @xmath104 which is perpendicular to the surface . along the @xmath33-direction and a macroscopic length of @xmath40 along the @xmath77-direction . we consider a cross - section a @xmath105 . ( b ) indexes of positions in the cross - section a. we label @xmath106 , @xmath107 , @xmath108 , @xmath109 , and @xmath110 as 1 " , 2 " , 3 " , 4 " , and 5 " . paths @xmath111 , @xmath112 , @xmath113 , and @xmath114 along the @xmath77-axis are labeled as i " , ii " , iii " , and iv".,width=321 ] we solve eqs . by the numerical integration toward the @xmath45-direction for @xmath115 and toward the @xmath55-direction for @xmath116 from the surface to the position @xmath46 . since @xmath101 , the initial value of @xmath115 at a surface @xmath99 is determined by the numerical integration toward the @xmath117-direction from the other surface to @xmath99 . eventually , we have to solve the numerical integration along the sufficiently long path by changing the direction from @xmath45 to @xmath117 at the surface so that the integration path gives the same value of @xmath115 under arbitrary initial values , and also @xmath116 . since the integration path changes the direction at the surface , simple calculation is difficult . for overcoming the difficulty , we exploit that the change in the direction of the integration path from @xmath45 to @xmath117 can be regarded as the change in the relative momentum of the pair potential from @xmath45 to @xmath117 . for example , we can substitute @xmath118 for @xmath119 in the pair potential instead of the reflection of the integration paths at a surface @xmath120 . similarly for the other surfaces , we can integrate eqs . along the straight long paths in the region connected to the antiperiodic pair potential infinitely . we calculate the quasi - classical green s function in a range @xmath121 and @xmath122 instead of a cross - section a @xmath105 to reduce computational time . we show the reduction method in appendix in addition to other reduction methods with the symmetry of the quasi - classical green s function . we discuss here the situation in which the thickness of a slab @xmath97 is changed , where the a- and b - phases are stable in thin and thick slabs , respectively . @xcite we present the calculated results of op , ldos , and mass current for the a - phase and spin current for the b - phase at @xmath123 . in each phase , the results depend on the thickness @xmath97 . the length of the cross - section a is taken as @xmath124 throughout the paper where the op is recovered to the bulk value at the center of the system . note that the following results are unchanged for the length @xmath40 longer than @xmath125 . in addition , we consider the low pressure limit @xmath126 within the weak - coupling limit . the spatial positions of the results are indicated by the indexes in fig . [ system](b ) . in this section and next section , we use the units @xmath127 , @xmath38 , and @xmath60 for length , energy , and ldos , respectively . the bulk of the a - phase is in the chiral state . the op in the chiral state is described by @xcite @xmath128 where @xmath85-vector and @xmath129-vector are perpendicular to each other . @xmath1-vector , which signifies the orbital chirality , is defined as @xmath130 . at the edge of a slab , since the normal orbital component to the edge vanishes , the polar state will be realized . the op in the polar state is described by @xcite @xmath131 where we regard @xmath129-vector as perpendicular to the edge . in a slab cell used by bennett _ et al . _ @xcite where the thickness is 0.6 @xmath24 m @xmath132 , it is expected that the a - phase is stable at @xmath123 . @xcite since the thickness @xmath97 is much shorter than the dipole coherence length @xmath133 , @xmath83-vector , which characterizes the spin state of the op in the a - phase , points to the @xmath33-direction in the absence of a magnetic field as long as @xmath1-vector is parallel to the @xmath33-axis . @xmath1-vector is parallel to the @xmath33-axis everywhere except near the side edges at @xmath120 and @xmath134 in the slab shown in fig . [ system ] . the length scale of the spatial variation of @xmath1-vector is short , whose order is the coherence length . on the other hand , @xmath83-vector can not vary spatially since the order of the length scale is the dipole coherence length . @xmath83-vector is spatially uniform even under a magnetic field . @xcite in this paper , we fix the direction of @xmath83-vector to the @xmath33-axis . for @xmath136 , the op is described by @xmath137 , where the relative phase between @xmath138 and @xmath139 is @xmath140 . the op is uniform along the @xmath33-direction and varies along only the @xmath77-direction . since the slab is thin , the @xmath31-component of the op is suppressed . note that the uniformness along the @xmath33-direction and the suppression of the @xmath31-component are not suppositions like in the previous work , @xcite but results by the self - consistent calculation . the profile of the op along the @xmath77-axis is shown in fig . [ as](a ) . because of the specular boundary condition , the @xmath141-component perpendicular to the edge becomes zero at @xmath120 and @xmath134 . in contrast , the parallel @xmath142-component is enhanced by compensating for the loss of the @xmath141-component at the edge , where the polar state is realized . the @xmath141-component increases and the @xmath142-component decreases toward the bulk region around @xmath143 ; thus , the chiral state with @xmath144 is attained . we can construct @xmath1-vector as @xmath145 , where @xmath146 is the totally antisymmetric tensor and @xmath147 is the squared amplitude of the op . @xmath1-vector points to the @xmath33-direction in the bulk region and vanishes at the edge . since the chiral state is realized except at the edge , the majorana fermion edge state @xmath3 exists at side edges . @xcite the mass current @xmath148 is shown in fig . [ as](b ) . the mass current flows circularly along the side edge of the slab . experimental values @xcite are used as coefficients of eq . so that a quantitative value of the mass current is obtained . by applying a magnetic field perpendicular to a slab , we can produce a spin imbalance due to the zeeman shift between the up - up spin pairs and the down - down spin pairs . this results in a net spin current in addition to the mass current . figure [ as](c ) shows ldos at the edge @xmath120 ( the position 2 " in fig . [ system ] ) and the bulk @xmath143 ( 5 " ) . it is clearly seen from the line 2 " for @xmath120 that the ldos with a substantial weight appears at a zero - energy , corresponding to the majorana edge mode , because the distance @xmath40 between the edges is macroscopic . @xcite this implies that the ldos is expressed as @xmath149 in the vicinity of @xmath150 . the first term comes from the majorana edge mode , and the second term comes from the point node of the chiral state in the bulk a - phase . the peak at @xmath151 comes from the gap of the chiral state in the bulk and the peak at @xmath152 comes from the gap of the polar state at the edge . the ldos at @xmath143 ( the line 5 " ) shows a typical behavior of the point node spectrum , namely , @xmath153 . in fig . [ as](d ) we show the extent of the majorana edge mode at @xmath150 toward the bulk from the edge at @xmath120 , which spreads over the order of @xmath154 . the spectrum of the edge gradually changes into the bulk spectrum . the ldos @xmath155 is obtained by averaging the angle - resolved ldos @xmath92 on the fermi surface , which has the peak at the energy of the surface andreev bound state . the dispersion relation of the surface andreev bound state can be evaluated by following the peak in each momentum direction . the angle - resolved ldos @xmath156 with @xmath157 and @xmath158 with @xmath159 are shown in figs . [ as](e ) and [ as](f ) , respectively , where @xmath160 is the polar angle from the @xmath31-axis and @xmath161 is the azimuthal angle from the @xmath141-axis on the three - dimensional fermi sphere . the angles and momentum directions have the relations : @xmath162 and @xmath163 . the angle - resolved ldos is symmetric between @xmath164 and @xmath165 , and between @xmath166 and @xmath167 . the zero - energy peaks of the angle - resolved ldos appear if @xmath157 except for @xmath168 . the zero - energy peaks come from the zero - energy andreev bound state of qps at the edge . the qps without the @xmath142-component have the zero - energy andreev bound state because they feel the @xmath169-phase shift of the pair potential for the relative momentum from @xmath170 to @xmath171 . this is clear from the eilenberger equation since the quasi - classical green s function @xmath172 depends on only the @xmath45-component of the pair potential @xmath144 . the angle - resolved ldos is asymmetric with respect to @xmath150 ( fig . [ as](f ) ) because the superfluid state in the a - phase has the chirality . @xcite the asymmetric angle - resolved ldos is related to the mass current . the peak energy of angle - resolved ldos at the side edges as a function of @xmath31 for @xmath173 and as a function of @xmath142 for @xmath174 is shown in figs . [ as](g ) and [ as](h ) , respectively . it is found that the energy is dispersionless along the @xmath31-axis and two linear dispersions appear near @xmath150 along the @xmath142-axis , where each dispersion comes from the left ( @xmath120 ) and right ( @xmath134 ) edges . since the directions of the mass current are different both edges , the linear dispersions have the opposite slope . the linear dirac dispersions continue along the @xmath31-direction , which form a `` dirac valley '' . the results are consistent with the strict quantum level structures of the majorana fermion edge state by bogoliubov - de gennes equation . @xcite in a thick slab , the @xmath31-component of the op is induced . for @xmath175 , the @xmath31-component appears near the edges at @xmath120 and @xmath134 to avoid the polar state except at @xmath111 and @xmath113 , shown in figs . [ a - op](a)-[a - op](c ) . the op is described by @xmath176 , where the phases of @xmath177 and @xmath138 are the same and the relative phase between @xmath177 and @xmath139 is @xmath140 . since the thickness of @xmath175 is small , the @xmath177 does not recover the bulk value of @xmath138 at the side edges @xmath120 and @xmath134 along @xmath112 ( fig . [ a - op](c ) ) . as similarly at the edges @xmath111 and @xmath113 , @xmath1-vector is perpendicular to the edges at @xmath120 and @xmath134 by the induced @xmath31-component , shown in fig . [ a - op](d ) . -vector texture in the @xmath77-@xmath33 plane of a slab.,width=321 ] the mass current @xmath178 is shown in fig . [ al](a ) , and its profiles along i " ( @xmath111 ) , ii " ( @xmath112 ) , and iii " ( @xmath113 ) are shown in fig . [ al](b ) . the mass current flows clockwise relative the local @xmath1-vector direction . the @xmath179 from @xmath1-vector in the bulk region flows to the negative ( positive ) @xmath78-direction at @xmath120 ( @xmath134 ) . at the side edges , since @xmath1-vector points to the negative @xmath77-direction , the @xmath179 from the edges flows to the negative and positive @xmath78-directions in @xmath180 and @xmath181 , respectively . therefore , the edge mass current is strengthened in @xmath180 ( @xmath181 ) and weakened in @xmath181 ( @xmath180 ) at the edge @xmath120 ( @xmath134 ) . the symmetry of the mass current between @xmath180 and @xmath181 is broken despite the symmetry of the op . figure [ al](c ) shows ldos at @xmath182 @xmath183 @xmath184 , @xmath107 , @xmath108 , and @xmath110 . at @xmath184 and @xmath108 ( the lines 1 " and 3 " ) , there are the zero - energy ldos and a small peak at a low energy indicated by the arrow in fig . [ al](c ) . although @xmath1-vector points to the edge , the zero - energy ldos also exists at @xmath107 ( the line 2 " ) . the lines 1 " and 3 " are slightly decreased and increased , respectively , in low energy from the small peak as energy increases . the line 2 " is almost constant in low energy . the ldos ( the lines 1 " , 2 " , and 3 " ) are enhanced sharply near @xmath185 . the ldos at @xmath110 ( the line 5 " ) shows the typical spectral behavior of the point node . in fig . [ al](d ) we show the extent of the zero - energy edge mode toward the bulk from the edge at @xmath120 . the amounts of the zero - energy ldos at @xmath120 along @xmath112 and @xmath113 ( the lines ii " and iii " ) are smaller than that along @xmath111 ( the line i " ) . the extent of the zero - energy ldos along iii " is of the order of @xmath154 as in the thin slab @xmath136 ; however , the zero - energy ldos along i " and ii " are more widely extended . the angle - resolved ldos @xmath186 with @xmath157 at @xmath184 , @xmath107 , and @xmath108 are , respectively , displayed in figs . [ al](e ) , [ al](f ) , and [ al](g ) . the zero - energy peaks of the angle - resolved ldos appear except for @xmath168 . the peaks of the line @xmath168 at the finite low energy appear from the upper and lower surfaces because the @xmath31-component of the pair potential is non - vanishing . since thickness @xmath175 is small , the original zero - energy peak of @xmath168 perpendicular to the upper and lower surfaces is split into the finite energy peaks , which is discussed particularly for the b - phase in next section . the splitting peaks at @xmath184 are shown in fig . [ al](h ) only at @xmath187 for @xmath173 . the finite energy peaks compose the small peak of the ldos in the lines 1 " and 3 " in fig . [ al](c ) . since the position @xmath107 is apart form the upper and lower surfaces , the energy peaks of @xmath168 are small . consequently , the peak of the ldos at low energy is not clear ( the line 2 " in fig . [ al](c ) ) . the point nodes of the op near the side edges have a tilt to the @xmath77-direction according to @xmath1-vector , or the anti - nodes of the op lie to some angles from the @xmath31-axis . thus , the incident qps from @xmath184 with low angles from the @xmath31-axis do not feel the clear small gap in the vicinity of the point nodes . for instance , the line @xmath188 in fig . [ al](e ) should be compared with that in fig . [ as](e ) for the thin slab @xmath136 . therefore , the gap - like ldos enhanced sharply near @xmath185 appears ( the line 1 " in fig . [ al](c ) ) . on the other hand , the incident qps from @xmath108 with low angles from the @xmath31-axis are reflected at the edge and regarded as with low angles from the @xmath189-axis . since the qps feel the small gap in the vicinity of the point nodes , they have the clear peaks in the angle - resolved ldos ( fig . [ al](g ) ) . therefore , the ldos is slightly increased in low energy as energy increases ( the line 3 " in fig . [ al](c ) ) . since the qps at @xmath107 have the two kinds of the characteristic momentum , the ldos is almost constant in low energy ( the line 2 " in fig . [ al](c ) ) . the ldos at the side edge is different and depends on the thickness of the slab . in the thin slab ( @xmath136 ) , @xmath1-vector points to the @xmath33-direction everywhere and the ldos is @xmath190 in low energy . in contrast , in the thick slab ( @xmath175 ) , @xmath1-vector points to the @xmath77-direction near the side edge and the ldos is @xmath191 , where @xmath192 is almost zero in low energy and increases sharply near @xmath185 like the ldos with the full gap state . the edge mass current varies along the side edge in the thick slab , which is also a great difference with the thin slab . note that the a - phase is metastable in the slab with @xmath175 at @xmath123 in the weak - coupling limit for @xmath126 . @xcite in the same slab , the a - phase is stabilized at @xmath193 ; @xcite however , @xmath1-vector points to only the @xmath33-direction , because the @xmath31-component is absent owing to the longer coherence length at higher temperature . the mechanism is similar to that the a - phase is more stable than the b - phase , which has the @xmath141- , @xmath142- , and @xmath31-components , in a thin slab at low temperature . the calculated results shown in this subsection is not in free energy minimum at @xmath27 ; however , the strong - coupling effect by pressure stabilizes the a - phase texture . thus , the above characteristics from the texture will be observed at finite pressure . the b - phase is stable when the thickness of a slab is larger than @xmath194 at @xmath123 . @xcite the op of the b - phase is described by @xcite @xmath195 where @xmath196 is a rotation matrix with a rotation axis @xmath197 and a rotation angle @xmath198 about @xmath197 . the rotation matrix gives the relative angle between the orbital momentum and the direction along which the spin of a cooper pair is zero . the spin state is stable by the dipole - dipole interaction when @xmath199 and @xmath197 is perpendicular to the surface in the absence of a magnetic field . @xcite if the thickness of a slab is much smaller than the dipole coherence length , @xmath197 is locked to the @xmath33-axis . thus , we derive @xmath200 , @xmath201 , and @xmath202 with the uniform rotation matrix @xmath203 . note that the three components have the same phase . at the surface of a slab , since the normal component to the surface of the orbital state vanishes , the planar state will be realized . the op in the planar state is described by @xcite @xmath204 where we regard the @xmath33-axis as perpendicular to the edge . if @xmath205 , the op can be written by other descriptions as @xmath206 where @xmath207 , @xmath208 , and @xmath209 . therefore , in the planar state , @xmath210 spin state has @xmath211 orbital angular momentum and @xmath212 spin state has @xmath213 orbital angular momentum . we consider that the thickness of a slab is much longer than the coherence length , namely , the thickness can be regarded as macroscopic for the op , and much shorter than the dipole coherence length . the requirement is satisfied for a thickness of @xmath214 . it is clearly seen that the component of the op perpendicular to the edge becomes zero in fig . [ b - op](a ) . the polar state @xmath142 occurs at the corner 1 " ( @xmath215 ) . the planar state @xmath216 for the up - up spin cooper pairs and @xmath144 for the down - down spin cooper pairs is attained in the middle region around 4 " ( @xmath217 ) , shown in fig . [ b - op](b ) . the planar state @xmath218 is realized at the side edge 2 " ( @xmath219 ) and the op is recovered to the bulk value of the b - phase around 5 " ( @xmath220 ) , shown in fig . [ b - op](c ) . at all edges ( @xmath120 , @xmath134 , @xmath111 , and @xmath113 ) , the majorana fermion edge state exists . @xcite the spin current @xmath221 , @xmath222 , @xmath223 , and @xmath224 are shown in fig . [ b - c](a ) . since the spin current flows in the three - dimensional real space , we show the schematic flow of the spin current in fig . [ b - c](b ) . the spin current for the @xmath76-component of spin turns around the @xmath76-axis . this is understandable as follows : since the up - up spin cooper pairs have negative chirality and the down - down spin cooper pairs have positive chirality , the @xmath33-component of the spin current turns around the @xmath33-axis . other components are also understood in the same manner . note that the schematic flow in fig . [ b - c](b ) is derived from @xmath225 before rotation by @xmath203 . the rotation axes for the @xmath77- and @xmath78-component of the spin current are changed correspondingly . . the unit of the spin current is @xmath226 @xmath227 . ( b ) a schematic flow of the spin current for @xmath228 , @xmath229 , and @xmath230 components.,width=321 ] figure [ bl](a ) shows the ldos . it is seen that only the line 1 " ( @xmath215 ) has the zero - energy ldos from the zero - energy andreev bound state of qps without the @xmath142-component . the lines 2 " and 4 " ( @xmath219 and @xmath217 ) are almost the same and show the linear relation @xmath231 near @xmath150 which reflects the surface andreev bound states . @xcite the line 5 " ( @xmath220 ) corresponds to the bulk ldos where the full gap is expected . in fig . [ bl](b ) we show the extension of the zero - energy state toward the middle from the edge at @xmath120 . the zero - energy ldos of the line i " ( @xmath111 ) reduces sharply as approaching the middle region from the edge . it is found that the value @xmath232 in the line iv " ( @xmath233 ) is much smaller than that of the line i " . the line ii " along @xmath112 shows the absence of the zero - energy ldos . therefore , we conclude that the zero - energy ldos is localized at the corner of the order of @xmath28 . the peak energy of the angle - resolved ldos is shown in figs . [ bl](c ) for the side edge and [ bl](d ) for the lower surface . figure [ bl](c ) is as a function of @xmath142 for @xmath174 and as a function of @xmath31 for @xmath173 at 2 " ( @xmath219 ) . figure [ bl](d ) is as a function of @xmath141 for @xmath173 and as a function of @xmath142 for @xmath234 at 4 " ( @xmath217 ) . these show that the side edge and lower surface have the same dispersion relation for low energy . the linear dispersion forms the majorana cone at the surface . @xcite the peak energy of the angle - resolved ldos at the corner @xmath184 is shown in figs . [ bl](e ) and [ bl](f ) . the energy is dispersionless along the @xmath31- and @xmath141-axes for @xmath173 . the dirac valley - type dispersion is composed of the zero - energy ldos at the corner ( the line 1 " in fig . [ bl](a ) ) . this is different from the majorana cone at the surface . . ( a ) ldos @xmath235 at 1 " , 2 " , 4 " , and 5 " . ( b ) zero - energy ldos @xmath236 along i " , ii " , and iv " ( @xmath233 ) . the peak energy of angle - resolved ldos as a function of @xmath142 for @xmath174 and as a function of @xmath31 for @xmath173 at 2 " ( c ) , and as a function of @xmath141 for @xmath173 and as a function of @xmath142 for @xmath234 at 4 " ( d ) . ( e ) and ( f ) are the same plots as ( c ) and ( d ) , but at 1".,width=321 ] we consider @xmath175 in thickness of a slab which is the critical thickness for stabilizing the b - phase below which the stripe phase becomes stable . @xcite since the thickness is short , the @xmath31-component of the op can not completely recover the bulk value . except that the @xmath31-component is reduced , the qualitative features of the op and the spin current are the same in the case of @xmath214 ; however , the ldos shows different spectrum . figure [ bm ] shows the ldos and the peak energy of the angle - resolved ldos , which are compared with those in fig . the differences between them are following : since the thickness of the slab is short , the line 5 " for the center ( @xmath220 ) has the spectrum from the full gap and the linear relation near @xmath150 , shown in fig . [ bm](a ) . the latter comes from the contributions extending from the upper and lower surfaces . the line 2 " for the side edge ( @xmath219 ) in fig . [ bm](a ) has the small peak at @xmath237 composed of the deformed majorana cone in @xmath238 , shown in fig . [ bm](c ) , because the qps with the @xmath31-component reflect that the @xmath31-component of the op does not recover the bulk value . the peak energy at 4 " for the lower surface in fig . [ bm](d ) implies that the lowest energy of the majorana cone is lifted from zero because of the tunneling of the zero - energy modes bound at two surfaces corresponding to the upper and lower surfaces . for the same reason , the zero - energy modes at the corner is split for @xmath187 in fig . [ bm](e ) and for @xmath173 or @xmath234 in fig . [ bm](f ) . by the energy splitting , the zero - energy ldos is slightly reduced ; however , the extension of the zero - energy state is the same for the thick slab @xmath214 , shown in fig . [ bm](b ) . , but for the b - phase with @xmath175.,width=321 ] the lowest energy of the majorana cone at the lower surface is more lifted from the zero - energy as the thickness is shorter . if the thickness is macroscopically long , the zero - energy modes appear , shown in the left panel of fig . [ split](a ) for the b - phase at 4 " ( @xmath217 ) with @xmath214 . when the thickness is short , the zero - energy modes bound at two surfaces are hybridized with each other . they form the symmetric and anti - symmetric states with the opposite sign energy @xmath239 and @xmath240 , respectively , where @xmath241 . the representative dispersion relation with @xmath242 is shown in the middle panel in fig . [ split](a ) . in the case of more shorter thickness , the b - phase becomes the planar phase , which is metastable against the a - phase , because the @xmath31-component of the op vanishes . since the fermi surface has the point nodes toward the direction of @xmath243 , the angle - resolved ldos toward the direction corresponds to that of the normal state without the peak energy . we show the dispersion relation with @xmath136 except the point @xmath243 in the right panel in fig [ split](a ) . there is a difference between the dispersion relations for @xmath242 and @xmath136 also in long wavelength which are curved and linear , respectively . the dependence of the energy splitting on the thickness is shown in fig . [ split](b ) . the energy splitting has the relation @xmath244 , where @xmath245 is effective coherence length . the exponential suppression is similar to the energy splitting of the majorana zero - energy modes bound at two vortices in a chiral @xmath4-wave superfluid . @xcite for @xmath173 and as a function of @xmath142 for @xmath234 with several thicknesses @xmath214 , @xmath246 , and @xmath247 . ( b ) the dependence of the energy splitting on the thickness . the dashed line is proportional to @xmath248 . , width=321 ] in the a - phase which has point nodes , since the zero - energy qps appear on the line @xmath173 in the momentum space , the zero - energy qps are dispersionless along the @xmath31-direction ( fig . [ as](g ) ) . therefore , the dispersion of the qps forms the dirac valley and the zero - energy ldos spreads over the order of @xmath154 from the side edge ( figs . [ as](c ) and [ as](d ) ) . in contrast , since the op in the b - phase has full gap on the fermi surface , only the qps with the momentum perpendicular to the edge are the zero - energy majorana qps . therefore , the dispersion of the qps forms the majorana cone ( figs . [ bl](c ) and [ bl](d ) ) . however , at the corner , the dispersion of the qps forms the dirac valley and the zero - energy ldos spreads over the order of @xmath28 . types of dispersion relation for the a- and b - phases are summarized in table [ tab ] . 15cm@ccccc ' '' '' & & upper or lower surface & side edge & corner + ' '' '' a - phase & thin slab ( @xmath135 ) & @xmath25 & dirac valley & dirac valley + ' '' '' & thick slab ( @xmath37 ) & @xmath25 & dirac valley & dirac valley + ' '' '' b - phase & thin slab ( @xmath37 ) & @xmath25 & majorana cone & dirac valley + ' '' '' & thick slab ( @xmath36 ) & majorana cone & majorana cone & dirac valley + the spin degeneracy of the qps is also different between the a- and b - phases . in the a - phase , since the up - up and down - down spin cooper pairs have the same chirality , the low energy qps have the degenerate branch of the dispersion at the edge ( fig . [ as](h ) ) . in the b - phase , since the up - up and down - down spin cooper pairs have the opposite chirality , the low energy qps have two branches of the dispersion at the edge ( fig . [ bl](c ) ) . this difference manifests itself in the edge current , namely , the mass current in the a - phase ( fig . [ as](b ) ) and the spin current in the b - phase ( fig . [ b - c ] ) . we discuss the majorana zero modes at a domain wall in the stripe phase . @xcite we take the thickness of a film along the @xmath33-direction and the modulation of the op along the @xmath77-direction . in the stripe phase , the @xmath31-component of the op changes the sign at the domain wall perpendicular to the @xmath77-direction so that the pair breaking by the reflection at the surface of the film is prevented . then , the op is described as @xmath249 to the right of the domain wall and @xmath250 to the left of the domain wall , where @xmath251 is finite everywhere and @xmath252 vanishes at the domain wall . the qps with the @xmath31-component across the domain wall have the finite energy andreev bound states because they feel the sign change of the @xmath31-component of the pair potential , which is not the exact @xmath169-phase shift . in addition , since the qps with @xmath174 feel the full gap of the pair potential , they are not excited in low energy . therefore , the majorana zero - energy qp is absent at the domain wall in the stripe phase . the domain wall is qualitatively different from the edge . there are several experimental means to detect the majorana nature . surface specific heat measurement , which was performed in connection with detection of the andreev surface bound state , @xcite resolves the side edge contribution @xmath253 of the a - phase in a thin slab at low temperatures , where @xmath254 , because the bulk contribution @xmath255 which comes from point nodes where @xmath256 is distinguishable . note that , in the a - phase , the contribution from the two upper and lower specular surfaces in the slab geometry is the same as that from the bulk . thus , the surface specific heat @xmath253 of the majorana qps is distinctive . if the @xmath1-vector direction is modulated near the side edge , the ldos at the surface is @xmath191 . the surface specific heat from the ldos is also @xmath253 . in the b - phase , the zero - energy ldos is localized at the corner of the order of @xmath28 . the contribution from the corner is interesting but smaller than that of the surface . since we will discriminate @xmath257 from the gap @xmath20 and @xmath258 from the linear behavior of ldos @xmath231 near @xmath150 , the majorana fermion can be observed . in the slab with short thickness where the zero - energy modes are split at the upper and lower surfaces , the difference of the specific heat from the surface and bulk will not be distinctive because the gap structure and linear behavior of the ldos coexist . the observation of the edge mass current in the a - phase , which is intimately connected with the intrinsic angular momentum , @xcite is also hopeful . the magnitude of the edge mass current is unchanged in wider slabs than @xmath124 for which we have calculated . considering the observation of the torque from the edge mass current for a 10 mm @xmath25 7 mm @xmath25 0.6 @xmath24 m slab sample ( bennett _ et al . _ @xcite had been used ) by a typical torsional oscillator , the frequency shift from the edge mass current is of the order of @xmath259 hz . @xcite the torque is too small to observe by a torsional oscillator because the magnitude is @xmath260 , where @xmath261 is the total number of @xmath0he atoms in the slab sample . we have to consider other experimental methods . also the edge spin current in the b - phase which flows three - dimensionally has been obtained quantitatively . the techniques to detect the spin current is desired . the specific experimental proposal to observe the edge current is a future problem . the most direct evidence of the majorana nature is derived from the observation of the anisotropic spin susceptibility . if we use the majorana nature of the edge state , in the a - phase , the local spin operators result in @xmath262 and only @xmath230 parallel to @xmath83-vector remains nontrivial for @xmath263 . @xcite this predicts the ising - like spin dynamics for the local spin operator parallel to @xmath83-vector in the a - phase as well as that perpendicular to the edge in the b - phase . @xcite this is in sharp contrast to the susceptibility parallel to @xmath83-vector in the bulk a - phase which is suppressed at low temperatures according to the yosida function . on the other hand , the susceptibility perpendicular to @xmath83-vector still assumes the bulk value , which is the same as it in the normal state . the anisotropic susceptibility has been discussed also by shindou _ et al . _ @xcite and has been calculated in the b - phase by nagato _ et al . _ @xcite qp scattering or qp beam experiments are extremely interesting . they were performed in the past on @xmath98he where roton - roton scattering is treated @xcite and on the @xmath0he b - phase where the surface andreev bound state is investigated . @xcite using this method , we may pick up majorana qps with a particular wave number . particularly in the a - phase , the majorana qps from the edge is separated from other qps from the nodal region . another option might be to use a free surface where the majorana fermion surface state is formed . as shown by kono , @xcite it can be detected through the excitation modes of the floating wigner lattice of electrons placed on the surface . we need a special , but feasible configuration of the experimental setups . note that the recent work of transverse acoustic impedance measurements to detect the surface bound states in the superfluid @xmath0he will derive the important information of the majorana qps . we have designed a concrete experimental setup to observe the majorana nature at the surface in the slab geometry . in connection with realistic slab samples , we have considered the upper and lower surfaces and the side edges including the corners with several thicknesses . we have demonstrated that the quasi - classical eilenberger equation yields the quantitatively reliable information on physical quantities for the superfluid @xmath0he a- and b - phases . specifically , we have exhibited the difference of ldos between the a- and b - phases and evaluated the mass current for the a - phase and the spin current for the b - phase quantitatively . then , we have shown the influence on the majorana zero modes from the spatial variation of @xmath1-vector for the a - phase in the thick slab and the energy splitting of the zero - energy modes for the b - phase confined in the thin slabs . the corner of the slab in the b - phase is accompanied by the unique zero - energy ldos of corner modes . in addition , we have demonstrated the absence of the majorana zero - energy qp at the domain wall in the stripe phase . on the basis of the quantitative consequences , it is proposed that the measurement of the specific heat , the edge current , and the anisotropic spin susceptibility provides feasible and verifiable experiments to check the majorana nature . the control on the thickness of the slab is crucial to detect the majorana surface states . the experiment controlling the thickness of the film of the superfluid @xmath0he is interesting . @xcite we thank t. mizushima for helpful theoretical discussions and k. kono , j. saunders , and y. okuda for informative discussions on their experiments . y. t. acknowledges the support of the research fellowships of the japan society for the promotion of science for young scientists . we use the symmetry of the quasi - classical green s function in eilenberger eq . to reduce computational time . if we replace matsubara frequency @xmath96 with @xmath264 , the quasi - classical green s functions in particle - hole space have relations @xmath265 where we describe the complex conjugate of the matsubara frequency explicitly because that is important when we calculate ldos . by the relations , we are allowed to sum only the positive @xmath96 to calculate self - consistent pair potential and mass and spin currents . if we reverse the sign of relative momentum @xmath45 , the sign of spin - triplet components of the op changes ; on the other hand , that of a spin singlet component of the op does not change . specifically , general op @xmath266 has a relation , @xmath267 , where a superscript t indicates transposition of a matrix . since the sign of fermi velocity also changes , @xmath268 , the quasi - classical green s functions in particle - hole space have relations @xmath269 more reduction of computational time is possible by using mirror operators which define @xmath270 , @xmath271 , and @xmath272 with an arbitrary vector @xmath273 . if the mirror operators act on the center - of - mass coordinate of pair potential under the antiperiodic boundary condition mentioned in sec . [ sec : sys ] , @xmath274 , where @xmath275 is one among @xmath228 , @xmath230 , and @xmath276 . since @xmath277 , the quasi - classical green s function satisfies @xmath278 therefore , the quasi - classical green s function and pair potential are obtained self - consistently by numerical calculation for only the positive matsubara frequency and one eighth of the fermi surface in the coordinate @xmath121 and @xmath122 by the symmetry of the quasi - classical green s function , , and . the calculation for the real space coordinates is carried out by parallel computing with openmp . 99ifxundefined [ 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 * * , ( ) link:\doibase 10.1103/physrevlett.66.3293 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.71.625 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevlett.86.850 [ * * , ( ) ] see the recent situations , for example , @noop * * , ( ) , and references therein @noop * * , ( ) @noop _ _ ( , , ) @noop _ _ ( , , ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1103/physrevb.52.490 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevb.78.214516 [ * * , ( ) ] @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1103/physrevb.23.5788 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevlett.103.107001 [ * * , ( ) ] link:\doibase 10.1103/physreva.82.023624 [ * * , ( ) ] link:\doibase 10.1103/physrevlett.96.125301 [ * * , ( ) ] y. okuda , private communication . link:\doibase 10.1103/physrevb.82.180505 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevlett.70.1846 [ * * , ( ) ] @noop * * , ( ) @noop * * , ( ) link:\doibase 10.1103/physrevlett.103.155301 [ * * , ( ) ] @noop * * , ( )

motivated by experiments on the superfluid @xmath0he confined in a thin slab , we design a concrete experimental setup for observing the majorana surface states . we solve the quasi - classical eilenberger equation , which is quantitatively reliable , to evaluate several quantities , such as local density of states ( ldos ) , mass current for the a - phase , and spin current for the b - phase . in connection with realistic slab samples , we consider the upper and lower surfaces and the side edges including the corners with several thicknesses . consequently the influence on the majorana zero modes from the spatial variation of @xmath1-vector for the a - phase in thick slabs and the energy splitting of the zero - energy quasi - particles for the b - phase confined in thin slabs are demonstrated . the corner of slabs in the b - phase is accompanied by the unique zero - energy ldos of corner modes . on the basis of the quantitative calculation , we propose several feasible and verifiable experiments to check the existence of the majorana surface states , such as the measurement of specific heat , edge current , and anisotropic spin susceptibility .

Thank you for your interest in spreading the word about Science. NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. ||||| Image copyright Jane Hill Image caption Painted lady butterflies were one of the larger species recorded in the study For the first time scientists have been able to track the hordes of high-flying insects that pass across the skies of Southern England every year. Unseen and unnoticed by humans, researchers found that 3.5 trillion bugs and butterflies annually migrate across the region. The researchers say their mass is equivalent to 20,000 flying reindeer. The count was made using vertical radar and insect nets mounted on balloons. Over a 10-year period, the scientists looked at insects flying night and day, between 150 and 1200m above the ground. While their origins weren't recorded the researchers believe that many were travelling to and from the UK from across the English Channel and the North Sea. Although the vast majority of the insects were tiny creatures like cereal crop aphids, flies and midges, there were also larger ones including hoverflies, ladybeetles, moths and butterflies. Image copyright Graham Shephard Image caption Vertical facing radar was used at several sites in Southern England to monitor the insects One of the most surprising findings was that while the smaller insects took off regardless of wind direction, all the medium and larger creatures showed a really clear pattern of seasonal movements. "The insects are basically measuring the wind direction and deciding whether or not to fly on that particular day or night," said Dr Jason Chapman, from the University of Exeter, the paper's co-author. "It signifies that the insects have a compass mechanism in order to know which is north and south, but they also have the capability to then fly up high into the sky and assess the direction of the wind and relate it to the compass direction and make a decision on whether to fly or not - that's a quite complex set of things and many, many species are doing this." The researchers found strong migrations northward in the Spring with subsequent movements south in the Autumn. The scale of these movements essentially cancelled each other out over the period of the study. Image copyright Ian Woiwood Image caption Insect nets attached to helium balloons were used to trap lower flying creatures What was also somewhat surprising were the distances covered and the speed of travel. The researchers found some insects were able to travel at 36-58 kilometres per hour, over distances of 200-300km. The ability to study these creatures over long periods of time may be very helpful in determining the changes to the environment. "Animal migration, especially in insects, is a very complex behaviour which takes millions of years to evolve and is very sensitive to climatic conditions," said Dr Ka S Lim, from Rothamsted Research, another author of the paper. Image copyright Ian Woiwood Image caption The silver Y moth is perhaps the UK's most common migrant moth "Global climatic change could cause decline of many species, but equally other highly adaptable species thrive and become agricultural crop pests." The researchers say that they have been able to estimate the mass of the creatures flying over the southern part of the UK at around 3,200 tonnes of biomass, which according to the authors is the equivalent of 20,000 flying reindeer. "It's also nearly eight times the mass of the number of migratory songbirds that are coming out of the UK every year," said Dr Chapman, "But yes, 20,000 reindeer is the correct figure, it's a calculation I did when I realised the date the paper was coming out!" The study has been published in the journal Science. Follow Matt on Twitter and on Facebook ||||| Radar spots trillions of unseen insects migrating above us Birds and human vacationers aren't the only creatures that take to the skies each year to migrate north or south. An analysis of a decade's worth of data from radars specifically designed to track airborne insects has revealed unseen hordes crossing parts of the southern United Kingdom—2 trillion to 5 trillion insects each year, amounting to several thousand tons of biomass, that may travel up to hundreds of kilometers a day. The numbers, reported in this week's issue of Science , are "stunning," says Silke Bauer, an ecologist at the Swiss Ornithological Institute in Sempach. "Wow," adds Larry Stevens, an evolutionary ecologist at the Museum of Northern Arizona in Flagstaff. "Can you image what these numbers look like in tropical settings, say, over the basins of the Amazon or the Congo?" Although some insect migrations are well known (think monarchs), the new work takes a systematic approach to flying insects and hints that such mass movements are surprisingly common. These airborne invertebrates, their bodies packed full of nitrogen and phosphorus, could move significant amounts of key nutrients across the globe. "Insects are little creatures, but collectively they can have a big impact; comparable in magnitude to large ocean migrations [of plankton]," says Lael Parrott, an environmental geographer at the University of British Columbia in Kelowna, Canada. In the 1970s, U.K. entomologists began to use mobile radars to assess movements of locusts and other pests in developing countries. By the late 1990s, they had designed a permanent upward-facing radar system, based at Rothamsted Research in Harpenden, U.K., that automatically logs insects of different sizes. In one early discovery, Jason Chapman, now at the University of Exeter in the United Kingdom, and colleagues found that certain large butterflies and moths that dwell in northern Europe in the summer and in the Mediterranean in the winter take advantage of favorable winds to migrate Annual migrations of flying insects Estimated biomass of migrating insects over southern United Kingdom recorded by radar and balloon flights. Now, Gao Hu, from Nanjing Agricultural University in China, Chapman, and colleagues have surveyed data from 2000 to 2009 collected in Harpenden and two other U.K. radar sites. The radars recorded medium-sized insects (hoverflies, ladybird beetles, and water boatmen) and large ones (hawk moths, painted lady butterflies, and aquatic beetles) flying between 150 meters and 1200 meters high; balloon sampling flights helped provide estimated counts for smaller insects. Directional seasonal migrations of flying insects The flow of insects north or south with the seasons may move a lot of nutrients across the United Kingdom. Among the medium and large insects, the radar documented 1320 mass migrations in the daytime and 898 at night over the course of the decade. These streams of insects, heading south in the fall and north in the spring, usually coincided with favorable winds, which swept them along at up to 58 kilometers an hour. That insects "have an idea of where they want to go to, when they want to go, and what winds are good [is] surprising for these tiny creatures," Bauer says. It will take more data, from other sites, to convince some entomologists that many insects migrate seasonally like birds and mammals. A European initiative is tracking birds using weather radars, and its scientists hope to get the funding to monitor insects as well. Such studies could be critical, notes zoologist Eric Warrant of Lund University in Sweden. "If, due to human influence, a large fraction of the [insect] migrant population is wiped out, it might have catastrophic consequences for those particular ecosystems." ||||| Bugs Abound: If You Think The Skies Are Crowded, You Have No Idea Enlarge this image toggle caption Ian Woiwod/Science Ian Woiwod/Science The holiday season is a time when lots of people take to the air, flying to see relatives or go on vacation. But when it comes to seasonal travel, humans are totally outnumbered by insects. That's according to a newly published study in the journal Science, which found that more than 3 trillion migrating insects fly over south-central England each year. "If you were to repeat this study almost anywhere else, I guarantee that you would exceed those numbers," says Jason Chapman, an entomologist at the University of Exeter, who notes that England is relatively cold and damp. Except for standouts such as the monarch butterfly, migrating insects have mostly been ignored by scientists who study migration, who tend to focus on charismatic birds like the Arctic tern and mammals such as the wildebeests of the Serengeti. "The insects have really not been studied in the way that they should have been," Chapman says. He points out that migrating insects can cause huge problems or bring real benefits. Consider the marmalade hoverfly, a small, insignificant-looking creature. "It's only about a centimeter long, it's orange with black stripes, but it's a hugely abundant migrant, and it actually does some very important jobs," Chapman says. This bug eats harmful aphids and pollinates crops as well as wildflowers. It spends the winter in the Mediterranean but comes to England in the spring. Chapman and his colleagues have spent about a decade monitoring the seasonal movement of insects like this hoverfly. They use specialized tools, including narrow beams of radar that point straight up, spotting the bigger insects that fly overhead. Smaller bugs have to be sampled using nets, which the researchers send up on little blimps. All of this lets them see which creatures fly up high, traveling with fast-moving air currents. "Those insects are the genuine long-range migrants," Chapman says. "They will be traveling at great speeds, and traveling for hundreds of kilometers in a single flight." In addition to the sheer number of migrating bugs overhead, his team found that most migration happens during the daytime. And overall, the northward movement of insects in the spring tended to cancel out the southward movement in the fall, but in some years there could be a real excess in either direction. Chapman hopes that similar studies could be done around the globe, allowing scientists to map how insects move around the world, carrying nutrients and diseases along with them. "It's just an awfully good study, using the techniques which they have developed," says Hugh Dingle, an expert on animal migration with the University of California, Davis. He personally wasn't surprised by the magnitude of these insect migrations, but said this is something that hasn't been well understood until now. "It's nice to see the data making this so apparent," Dingle says. "Certain insects like locusts and the monarch butterfly, have gotten a great deal of attention," Dingle adds. "But perhaps because of all that attention on these big charismatic insects, the huge migrations that occur in lots and lots of other insects, all the way down to tiny aphids, are certainly not as well known by the public, and may not even be as well known by scientists."

– Step outside and imagine there's a blanket of billions of insects overhead—because there probably is. Researchers who spent a decade tracking insects 500 to 4,000 feet above the ground in south-central England using radar beams and nets found about 3.5 trillion bugs and butterflies migrate across the region each year—moving south in the fall and north in the spring, much like birds. To picture it another way: Their mass is equal to about 20,000 airborne reindeer, reports the BBC. An ecologist says the number is "stunning," per Science, and another wonders how many more fly "over the basins of the Amazon or the Congo?" Indeed, "if you were to repeat this study almost anywhere else, I guarantee that you would exceed those numbers," study author Jason Chapman tells NPR, citing England's cold and wet conditions. While small insects weren't picky about wind direction, scientists were surprised to find that larger insects appeared to be more deliberate in choosing whether to fly given current wind direction. "It signifies that the insects have a compass mechanism in order to know which is north and south, but they also have the capability to then fly up high into the sky and assess the direction of the wind," compare the two, and decide what to do, which is "quite complex," Chapman says. The researchers also noted that the bugs weren't exactly leisurely flitting above. Some take advantage of fast-moving air currents to travel distances of up to 200 miles at speeds of up to 36 miles per hour. (Meet the world's longest-distance flier.)

echinococcus tapeworm eggs are passed in the feces of an infected carnivorous animal and may subsequently be ingested by humans ; they hatch into embryos in the intestine , penetrate the intestinal lining , and carried by blood throughout the body to major organs such as the liver , lungs , and heart . after the growing larvae localize in an organ , they transform into echinococcal cysts in which numerous tiny protoscolices are produced via asexual reproduction . in most patients , potentially it may cause right or left ventricular outflow obstruction , tricuspid regurgitation , aortic stenosis , myocardial dysfunction , conduction disturbances , stroke , or may lead to congestive heart failure . the most frequent location in the heart is left ventricular free wall and the interventricular septum [ 3 - 5 ] . clinical presentation of cardiac echinococcal cysts depends on the site , size , calcification , and number of cysts , integrity of the cyst , and presence of complications as the result of cyst rupture . dibello and menenotez reported that a cyst rupture into the pericardium may cause acute pericardial tamponade , secondary pericardial cysts , or constructive pericarditis . madariaga et al . showed that the rupture of subendocardial cysts , which otherwise may be silent , may cause anaphylactic shock and sudden death , peripheral and cerebral embolism , or pulmonary embolism . reported that intracavitary expansion and rupture of the cyst caused dyspnea or right outflow obstruction , pulmonary embolization , pulmonary hypertension , and death . ameli and dibello reported that acute coronary syndrome secondary to the compression or emboli to the coronary artery may mimic coronary artery disease . according to dighiero et al . , the resulting pain of pericarditis may radiate to the epigastrium and , it may closely mimic acute abdomen . other complications included mitral regurgitation ( mr ) , papillary muscle ischemia , atrioventricular conduction defects . in the present study , we encountered a 44-year - old male patient with hydatid disease in the intraventricular septum of the heart with papillary muscle involvement and clinical symptoms of dyspnea and chest pain . the preoperative diagnosis was established using echocardiography and confirmed after recovery of hydatid daughter cysts ( fig . a 46-year - old man non - smoker was admitted to our hospital due to dyspnea and chest pain for the last 4 months that exacerbated some days before admission . electrocardiogram ( ecg ) did not show any remarkable findings except for right bundle branch block ( rbbb ) . all routine laboratory test results , including liver and kidney function tests , serum proteins , and urine analysis were normal . the computed tomography ( ct ) scan of the abdomen and thorax showed no disease . transthoracic contrast echocardiography revealed a huge cyst like a hypodense structure ( 6555 mm ) , located in the interventricular septum and the base of papillary muscle with distortion of mitral wall apparatus ( i.e. , papillary muscles ) and moderate mr ( fig . the rest of examination was normal with an estimated ejection fraction of 45% , without regional wall motion abnormalities . the patient underwent median sternotomy , and excision of the cardiac cyst was planned by using cardiopulmonary bypass . the patient received albendazole preoperatively with the dose of 800 mg daily for 2 weeks . after a median sternotomy , the patient was connected to the cardiopulmonary bypass by cannulating the ascending aorta and superior and inferior vena cava . there was no sign of pericarditis , and pericardial cavity was free of fibrosis and adhesions . under a condition of hypothermic cardiopulmonary bypass , the aorta was cross - clamped and the heart was arrested with a dose of antegrade cold cardioplegia . the right atrium was opened that revealed bulging of the septum that was calcified as a white and hard mass in the right ventricular aspect of the septum ( fig . the pericardial cavity was localized by pad moistened by ethanol 96% , and 10 ml ethanol was injected to the cyst cavity and after 5 min non - viscous yellow painted fluid was aspirated . a large incision was made into the right ventricular aspect of the septum corresponding to cyst 's free wall . the sub - septal wall of the cyst was calcified , fibrotic , and was not excised but its contents included the glistening germinative layer and daughter cysts were sucked out ( fig . the cyst was then washed with 5 ml of povidone iodine solution , which was left inside for 5 min and then aspirated . the resultant cavity made by intraseptal partitioning was then obliterated by approximation of its fibrosis walls with 4 - 0 viline suture to complete this obliteration . we explored the left ventricle via the left atrium that revealed involvement of the base of huge anterior papillary muscle as a subsidiary horn . the septal involvement by the cyst caused distortion of the mitral apparatus by papillary muscle elongation . anterior mitral leaflet prolapse that has normal segment of the p1 and p2 scallops were repaired by means of corda tendina shortening . normalized lengthening of the papillary muscle and corda tendina eliminated moderate mr post - operatively . after operation , transesophageal echocardiography revealed a venticule septal defect ( vsd ) in the base of the anterior papillary muscle which was repaired with 4 - 0 viline sutures ( fig . the patient had an uneventful recovery and at the 7th postoperative day she was discharged from the hospital with an acceptable echocardiography findings which revealed near normal functions of the mitral valve apparatus , with only mild regurgitation . involvement of the heart by hydatid cysts can occur through the inferior vena cava to the right atrium and directly to the right atrial wall or trans - septaly through the interatrial septum to the left atrium or trans - septaly to the left ventricle or remains intra - septaly . another way is through the pulmonary artery to the lung and from the pulmonary vein to the systemic circulation or intra - heart cavity to any part of the heart structure like atria and ventricles but involvement of papillary muscles concomitantly with interventricular septum and mr is exceptionally rare and careful literature evaluation revealed only a few cases . . revealed that the prevalence of left and right atrium is 4% of heart structure involvement . documented that , due to the effect of pump , the left ventricle cysts perforated in the aorta but the right ventricle cysts perforated intracavitary . . showed that the incidence of intracardiac perforation is between 20 - 40% and after a cyst perforation 75% of the patients died from septic shock or embolic complications . heart is only organ that can be treated by surgery ; however , other organs may be treated both by chemotherapy and surgical manipulations . in the case of heart echinococcosis it is impossible to administer anthelmintic medications prior to a surgery due to the risk of cyst wall destruction and rupture . in addition , the results of surgical treatment of heart echinococcosis are better than those treated by the conservative strategy only . the present unusual and exceedingly rare case exemplifies that one has to keep the hydatid cyst in the differential diagnosis of a mixed echogenic mass in the interventricular septum on echocardiography that complicated preoperatively by mr and post - operatively by vsd . in view of the rarity of combined the septal and papillary muscle involvement by the hydatid cyst that complicated by pre - operative mr , surgical treatment of cardiac echinococcosis is emergent . in conclusion , the treatment of heart echinococcosis should be a combination of surgical intervention with chemotherapy during or post - operative period aiming to decrease the recurrences .

we present here a 44-year - old male patient with hydatid disease who was referred to our hospital due to dyspnea and chest pain for the last 2 month before admission . using echocardiography and contrast - enhanced computed tomography the heart hydatid was diagnosed . however , hydatid disease of the interventricular septum is rare ; particularly , the involvement of mitral apparatus with mitral regurgitation ( mr ) is an exceptionally rare presentation . early diagnosis and an integrated treatment strategy are crucial . surgical excision was performed and the patient had an uneventful recovery and follow - up at 3 months .

a longstanding problem in general relativity has been to find the general behavior of singularities . several results , both analytical@xcite and numerical@xcite have been obtained . though most of the results are for the case where the spacetimes have one or more symmetries , recent work has been done on the general case where there are no symmetries.@xcite there is a longstanding conjecture@xcite due to belinski , lifschitz and khalatnikov ( bkl ) that states that the generic singularity is spacelike and local . this conjecture has been reformulated and put more precisely by uggla _ et al_.@xcite the type of local dynamics conjectured by bkl depends on the type of matter . for vacuum and for many types of matter , the bkl conjecture is that the local dynamics is oscillatory , corresponding to the dynamics of a bianchi type ix spacetime . however , for stiff fluid ( _ i.e. _ fluid with pressure equal to energy density ) the bkl conjecture is that the local dynamics is asymptotically velocity term dominated corresponding to the dynamics of a bianchi type i spacetime . the vacuum version of the bkl conjecture has been supported by the numerical simulations of @xcite which show local and oscillatory dynamics in vacuum spacetimes with no symmetry . the stiff fluid version of the bkl conjecture has been supported by the theorem of andersson and rendall@xcite which shows the local existence in a neighborhood of the singularity of solutions of the einstein equations with stiff fluid matter with the expected asymptotic behavior and with enough degrees of freedom to be the generic solutions . what is not known is whether generic stiff fluid initial data evolves to a solution of the andersson and rendall class . to address this issue , we perform numerical simulations of the approach to the singularity for stiff fluid matter with no symmetries . our methods are those of @xcite using the system of @xcite . section ii presents the equations and numerical methods used . the results are given in section iii and conclusions in section iv . the system evolved here is essentially that of reference@xcite but specialized to the stiff fluid case and with a slightly different choice of gauge . here the spacetime is described in terms of a coordinate system ( @xmath0 ) and a tetrad ( @xmath1 ) where both the spatial coordinate index @xmath2 and the spatial tetrad index @xmath3 go from 1 to 3 . it is assumed that @xmath4 is hypersurface orthogonal and that the relation between tetrad and coordinates is of the form @xmath5 and @xmath6 here @xmath7 is the lapse and we have chosen the shift to be zero . we choose the spatial frame @xmath8 to be fermi propagated along the integral curves of @xmath4 . the commutators of the tetrad components are decomposed as follows : @xmath9 & = & { { \dot u}_\alpha}{{\bf e}_0 } -(h { { \delta _ \alpha}^\beta } + { { \sigma _ \alpha}^\beta } ) { { \bf e}_\beta } \label{com0i } \\ \left [ { { \bf e}_\alpha } , { { \bf e}_\beta } \right ] & = & ( 2 { a_{[\alpha}}{{\delta _ { \beta ] } } ^\gamma } + { \epsilon _ { \alpha \beta \delta } } { n^{\delta \gamma}}){{\bf e}_\gamma } \label{comij}\end{aligned}\ ] ] where @xmath10 is symmetric , and @xmath11 is symmetric and trace free . square brackets denote the antisymmetric part of a tensor . define @xmath12 and @xmath13 , that is @xmath14 is the timelike vector of the tetrad and @xmath15 is the spatial metric corresponding to the choice of @xmath14 as the time direction . then the stress - energy tensor can be decomposed as @xmath16 where @xmath17 and @xmath18 are orthogonal to @xmath14 and where @xmath18 is symmetric and trace - free . round brackets denote the symmetric part of a tensor . scale invariant variables are defined as follows : @xmath19 the matter variables are not all independent , because we assume that the stress - energy is that of a stiff fluid @xmath20 here @xmath21 is the rest frame energy density of the fluid and @xmath22 is the fluid four - velocity , which can be decomposed as @xmath23 where @xmath24 is orthogonal to @xmath14 . comparison of equations ( [ generalstress ] ) and ( [ stiffstress ] ) yields @xmath25 here @xmath26 and @xmath27 and angle brackets denote the symmetric trace - free part of a tensor . thus , all scale invariant matter variables can be expressed in terms of @xmath28 and @xmath29 . finally choose the lapse to be @xmath30 . the relation between scale invariant frame derivatives and coordinate derivatives is @xmath31 and @xmath32 . from the einstein field equations and the conservation of stress - energy one obtains the following evolution equations : @xmath33 { q^\beta } \bigr ) \\ & - & 2 { v^\alpha } \bigl ( { \partial _ t } \omega - 2 [ q+1 ] \omega \bigr ) \biggr ] \label{ev7 } \\ \nonumber { \partial _ t } q & = & \left [ 2 ( q-2 ) + { \textstyle \frac 1 3 } \left ( 2 { a^\alpha } - { r^\alpha}\right ) { \parb _ \alpha } - { \textstyle \frac 1 3 } { \parb ^\alpha}{\parb _ \alpha } \right ] q \\ \nonumber & - & { \textstyle \frac 4 3 } { \parb _ \alpha}{r^\alpha } + { \textstyle \frac 8 3}{a^\alpha}{r_\alpha } + { \textstyle \frac 2 3 } { r_\beta}{\parb _ \alpha}{\sigma ^{\alpha \beta } } - 2 { \sigma ^{\alpha \beta}}{w_{\alpha \beta } } \\ \nonumber & + & { \frac 2 { g_+ } } \biggl [ 2 \omega { \sigma ^{\alpha \beta } } { v_\alpha } { v_\beta } - 2 ( q-2 ) \omega + { \partial _ t } \omega \\ & - & { \frac { 2 \omega } { g_+ } } { v_\alpha } { \partial _ t } { v^\alpha } \biggr ] \label{ev8}\end{aligned}\ ] ] here we are using units where @xmath34 . furthermore the quantities @xmath35 , @xmath36 , @xmath37 and @xmath38 are given by @xmath39 in addition to the evolution equations , the variables satisfy constraint equations as follows : @xmath40{{e_\beta } ^i } \bigr ) \\ & - & { n^{\gamma \alpha } } { { e_\alpha } ^i } \label{cn1 } \\ \nonumber 0 & = & { { \cal c}_{\rm g } } \equiv 1 + { \textstyle \frac 1 3 } ( 2 { \parb _ \alpha } - 2 { r_\alpha } - 3 { a_\alpha}){a^\alpha } - { \textstyle \frac 1 6}{n_{\alpha \beta}}{n^{\alpha \beta } } \\ & + & { \textstyle \frac 1 { 12 } } { { ( { { n^\alpha}_\alpha})}^2 } - { \textstyle \frac 1 6 } { \sigma _ { \alpha \beta}}{\sigma ^{\alpha \beta } } - \omega \label{cn2 } \\ \nonumber 0 & = & { { ( { { \cal c}_{\rm c}})}^\alpha } \equiv { \parb _ \beta } { \sigma ^{\alpha \beta}}+ 2 { r^\alpha } - { { \sigma ^\alpha}_\beta } { r^\beta } - 3 { a_\beta}{\sigma ^{\alpha \beta } } \\ & -&{\epsilon ^{\alpha \beta \gamma}}{n_{\beta \delta } } { { \sigma _ \gamma}^\delta } + 3 { q^\alpha } \label{cn3 } \\ \nonumber 0 & = & { { \cal c}_q } \equiv q - { \textstyle \frac 1 3 } { \sigma ^{\alpha \beta } } { \sigma _ { \alpha \beta}}+{\textstyle \frac 1 3 } { \parb _ \alpha } { r^\alpha } - { \textstyle \frac 2 3}{a_\alpha}{r^\alpha } \\ & - & { \textstyle { \frac 1 2 } } ( \omega + 3 p ) \label{cn4 } \\ \nonumber 0 & = & { { ( { { \cal c}_{\rm j}})}^\alpha } \equiv { \parb _ \beta } { n^{\alpha \beta } } - ( { r_\beta}+ 2 { a_\beta}){n^{\alpha \beta } } \\ & + & { \epsilon ^{\alpha \beta \gamma } } ( { \parb _ \beta}{a_\gamma } - { r_\beta}{a_\gamma } ) \label{cn5 } \\ 0 & = & { { ( { { \cal c}_{\rm w}})}^\alpha } = { \epsilon ^{\alpha \beta \gamma } } \bigl ( { \parb _ \beta}{r_\gamma } - { a_\beta}{r_\gamma } \bigr ) - { n^{\alpha \beta}}{r_\beta } \label{cn6 } \end{aligned}\ ] ] we want a class of initial data satisfying these constraints that is general enough for our purposes but simple enough to find numerically . recall that on an initial data surface , the spatial metric @xmath41 and extrinsic curvature @xmath42 must satisfy the constraint equations @xmath43 here @xmath44 and @xmath45 are respectively the derivative operator and scalar curvature associated with @xmath41 and @xmath46 and @xmath47 are the components of the stress - energy tensor given in equation ( [ generalstress ] ) . we use the york method@xcite which begins by defining the quantities @xmath48 and @xmath49 by @xmath50 we choose @xmath51 to be constant , @xmath48 to be the flat metric @xmath52 and @xmath53 to vanish . with these choices , equations ( [ cmom ] ) and ( [ cham ] ) become @xmath54 here @xmath55 is the ordinary derivative with respect to cartesian coordinates and indicies are raised and lowered with @xmath52 . we choose space to have topology @xmath56 with the cartesian coordinates @xmath57 and @xmath58 each going from @xmath59 to @xmath60 . we choose the following solution of equation ( [ ymom ] ) @xmath61 with the off - diagonal components of @xmath49 vanishing . here the @xmath62 and @xmath63 are constants . note that due to the periodicity of the coordinates and the linearity of equation ( [ ymom ] ) the general solution of equation ( [ ymom ] ) is a fourier series . the solution that we choose is then essentially the simplest solution of equation ( [ ymom ] ) without symmetries . the quantity @xmath46 can be freely specified and we choose it to be @xmath64 where the @xmath65 are constants . with these choices for @xmath49 and @xmath46 , equation ( [ yham ] ) is solved numerically ( in a manner to be described later ) to yield @xmath66 and therefore @xmath41 and @xmath42 . from this initial data , we must then produce the initial values of the scale invariant variables . from equation ( [ com0i ] ) it follows that @xmath67 and since @xmath68 is constant it then follows that @xmath69 vanishes . since the initial spatial metric is conformally flat , we choose the initial spatial tetrad vectors by @xmath70 it then follows from equation ( [ comij ] ) that @xmath71 vanishes and that @xmath72 from equation ( [ com0i ] ) it then follows that @xmath73 while @xmath74 is given by equation ( [ si5 ] ) and @xmath75 by the vanishing of equation ( [ cn4 ] ) . the numerical method used is as follows : each spatial direction corresponds to @xmath76 grid points with spacing @xmath77 . the variables on grid points @xmath78 to @xmath79 are evolved using the evolution equations , while at points @xmath80 and @xmath76 periodic boundary conditions are imposed . the initial data is determined once equation ( [ yham ] ) is solved . this is done iteratively as follows:@xcite define @xmath81 then equation ( [ yham ] ) takes the form @xmath82 . we make an initial guess @xmath83 for @xmath84 and solve using the conjugate gradient method @xcite the equation @xmath85 iterating until @xmath86 satisfies equation ( [ yham ] ) to within a set tolerance . the evolution proceeds using equations ( [ ev1]-[ev8 ] ) with the exception that the term @xmath87 is added to the right hand side of equation ( [ ev8 ] ) to prevent the growth of constraint violating modes and the term @xmath88 is added to the right hand side of equation ( [ ev3 ] ) to make the system well posed.@xcite spatial derivatives are evaluated using centered differences , and the evolution is done using a three step iterated crank - nicholson method@xcite ( a type of predictor - corrector method ) . in equation ( [ ev8 ] ) the highest spatial derivative term is @xmath89 which gives this equation the form of a diffusion equation . note that diffusion equations can only be evolved in one direction in time , in this case the negative direction which corresponds to the approach to the singularity . stability of numerical evolution of diffusion equations generally requires a time step proportional to the square of the spatial step . however , the constant of proportionality depends on the coefficient of the second spatial derivative . to ensure stability , we define @xmath90 to be the maximum value of @xmath91 ( over all space and over all @xmath3 and @xmath2 ) and then define @xmath92 and @xmath93 . the time step @xmath94 is then chosen to be whichever of @xmath95 and @xmath96 has the smaller magnitude . before presenting numerical results , it is helpful to consider what behavior to expect as the singularity is approached ( that is as @xmath97 ) . first denote the eigenvalues of @xmath98 by ( @xmath99 ) . then suppose that at sufficiently early times the time averages of @xmath100 are all positive . then the time averages of the eigenvalues of @xmath101 are all positive . since we are evolving in the negative time direction , this should lead ( through equation ( [ ev1 ] ) ) to an exponential decrease in @xmath102 . however , since all spatial derivatives appear in the equations in the form @xmath103 we would expect the spatial derivatives to become negligible . that is , the approach to the singularity is local . furthermore , this positivity of the time averages of the eigenvalues of @xmath101 should lead ( through equations ( [ ev2]-[ev3 ] ) ) to exponential decrease in @xmath69 and @xmath104 . a similar argument applied to equations ( [ ev6 ] ) and ( [ dtqvec ] ) and using equations ( [ cn2 ] ) and ( [ cn4 ] ) indicates that as the singularity is approached @xmath105 should become negligible , but @xmath74 should not , and therefore that @xmath106 should become negligible . thus , as the singularity is approached , the system should be well described by a simplified set of evolution and constraint equations where spatial derivatives as well as @xmath107 and @xmath106 are negligible . note that the fact that spatial derivatives are becoming negligible does @xmath108 mean that the spacetime is becoming homogeneous . rather the considerable spatial variation is becoming a negligible part of the equations of motion since all spatial derivatives appear multiplied by @xmath102 which is becoming negligible . we now write down this simplified system of evolution and constraint equations where all these terms are neglected . in this limit equation ( [ cn3 ] ) implies that the matricies @xmath98 and @xmath109 commute and therefore have the same eigenvalues . the evolution equations for @xmath110 and @xmath111 can then be written as evolution equations for their eigenvalues . the non - trivial evolution and constraint equations then become in this limit @xmath112 @xmath113 here @xmath114 and @xmath115 are the eigenvalues of @xmath98 and @xmath109 respectively and @xmath116 is given by @xmath117 and indicies are not summed over unless explicitly indicated . suppose that the dynamics is in a period ( called a kasner epoch ) when all the @xmath115 are negligibly small . then it follows from equations ( [ trcn1 ] ) and ( [ trcn2 ] ) that @xmath118 and therefore , from equations ( [ trev1 ] ) and ( [ trev3 ] ) that @xmath74 and the @xmath114 are constant . from equations ( [ trcn1 ] ) and ( [ trev2 ] ) it follows that there are two possibilities for a kasner epoch : ( i ) all the @xmath114 are @xmath119 in which case the @xmath115 remain negligible and the kasner epoch lasts all the way to the singularity . ( ii ) one of the @xmath114 is @xmath120 in which case the corresponding @xmath115 grows until it is large enough to bring the kasner epoch to an end . we now look in more detail at possibility ( ii ) . let @xmath121 be the @xmath114 that is @xmath122 . then @xmath123 is the @xmath115 that is growing . we are therefore led to examine equations ( [ trev1]-[trcn2 ] ) neglecting @xmath124 and @xmath125 but not @xmath123 . in this regime equations ( [ trev1 ] ) and ( [ trev2 ] ) become @xmath126 where @xmath127 . define @xmath128 . then equation ( [ sig1ke ] ) becomes @xmath129 while from equations ( [ sig2ke ] ) and ( [ sig3ke ] ) it follows that there are constants @xmath130 and @xmath131 with @xmath132 such that @xmath133 and @xmath134 . similarly , it follows from equation ( [ omegake ] ) that there is a constant @xmath135 such that @xmath136 . finally , it then follows from equation ( [ trcn1 ] ) that @xmath137 satisfies the equation of motion @xmath138 z\ ] ] where @xmath139 $ ] . note that the quantity in square brackets vanishes at @xmath140 and @xmath141 where @xmath142 . therefore the dynamics is a `` bounce '' from a kasner epoch corresponding to @xmath141 to one corresponding to @xmath140 . use a minus subscript to denote a quantity before the bounce and a plus subscript to denote a quantity after the bounce . we then have @xmath143 . however , from the definition of @xmath137 it follows that @xmath144 while from the definition of @xmath145 it follows that @xmath146 . we then find the following `` bounce rule '' relating a quantity after the bounce to quantities before the bounce . @xmath147 note that from the bounce rule it follows that @xmath74 increases at each bounce . furthermore , it follows from equation ( [ trcn1 ] ) ( and from the fact that @xmath148 is trace - free ) that the minimum possible value for a @xmath114 during a kasner epoch is @xmath149 and therefore that no further bounces can happen once @xmath150 ( though bounces may cease at lower values of @xmath74 ) . thus we expect that at each spatial point there is a last bounce followed by a kasner epoch that lasts all the way to the singularity . in other words , we expect the approach to the singularity to be of the andersson and rendall class . all runs were done in double precision on a sunblade 2000 with @xmath151 ( except for a convergence test which also used @xmath152 ) . the equations were evolved from @xmath153 to @xmath154 . for the initial data , the trace of the extrinsic curvature was @xmath155 corresponding to an initial value of @xmath156 for @xmath68 . the constants @xmath157 and @xmath65 characterizing the initial data were @xmath158 and the constant @xmath159 was @xmath160 . we would like to know whether @xmath161 and @xmath29 become negligible as the singularity is approached . in figure 1 are plotted the maximum values ( over all space , @xmath162 and @xmath2 ) of @xmath163 and @xmath164 . note that after a certain amount of evolution , all these quantities steadily decrease . this indicates that after a certain amount of time spatial derivatives become negligible in the eqautions of motion and that the approximation considered at the end of the previous section becomes valid . maximum values of @xmath165 ( solid line ) , @xmath166 ( dotted line ) @xmath167 ( dot - dashed line ) and @xmath164 ( dashed line ) _ vs _ @xmath168 @xmath169 _ vs _ @xmath170 for the @xmath151 run ( solid line ) and @xmath171 _ vs _ @xmath170 for the @xmath152 run ( dotted line ) ] components of @xmath148 in the asymptotic frame _ vs _ @xmath121 ( solid line ) , @xmath172 ( dotted line ) and @xmath173 ( dot - dashed line ) ] components of @xmath71 in the asymptotic frame _ vs _ @xmath123 ( solid line ) , @xmath124 ( dotted line ) and @xmath125 ( dot - dashed line ) ] @xmath28 _ vs _ @xmath168 it then follows that the interesting part of the dynamics is the development of the variables at a single point as a function of time . we now present data of that form . the behavior at the spatial point chosen is typical . the results of a convergence test are plotted in figure 2 . here what is plotted is @xmath169 for the @xmath151 run ( solid line ) and @xmath174 for the @xmath152 run ( dotted line ) . both quantities are plotted _ vs _ @xmath170 . note that the two curves roughly agree in magnitude but become out of sync in time . this indicates second order convergence but with the system having sensitive dependence on initial conditions . similar results were obtained for the other constraints . figures 3 and 4 show respectively the diagonal components of @xmath148 and @xmath71 in the asymptotic frame , _ i.e. _ the frame of the eigenvectors that @xmath175 has at the end of the evolution . for that part of the evolution where the approximation made at the end of the previous section is valid , these diagonal components are the eigenvalues of @xmath176 and @xmath109 respectively . note that the dynamics of the eigenvalues of @xmath176 consists of epochs where they are apporoximately constant ( kasner epochs ) punctuated by short bounces . furthermore the components of @xmath71 are negligible except at the bounces . also note that there is a last bounce and that this coincides with the most negative eigenvalue of @xmath98 becoming greater than @xmath155 . in figure 5 is plotted @xmath74 _ vs _ @xmath170 . note that the behavior of @xmath74 is a sequence of constant values that are punctuated by short bounces and that the bounces in @xmath74 occur at the same times as the bounces in @xmath148 . the sequence of the values of @xmath74 is 0.05956 , 0.1607 , 0.4139 , 0.6231 , while the corresponding values of the most negative eigenvalues of @xmath177 are -1.583 , -1.565 , -1.277 , -0.6596 . these values obey the `` bounce rule '' of equation ( [ rlbounce ] ) . these simulations support the expected picture for the approach to the generic singularity in a spacetime where the matter is a stiff fluid . as the singularity is approached the terms in the equations of motion involving spatial derivatives become negligible . the dynamics at each spatial point consists of a sequence of kasner epochs punctuated by short bounces . the sequence of values of @xmath74 obeys the expected bounce rule . there is a last bounce , after which the dynamics is described by a single kasner epoch all the way to the singularity , thus yielding a spacetime in the class of reference @xcite . what remains to be done is to treat the approach to the singularity for non - stiff fluids . here the behavior that is expected is quite different . the bkl conjecture is that the matter will become negligible and the dynamics of the gravitational variables as the singularity is approached will be that of vacuum spacetimes . the formalism of @xcite includes a class of non - stiff fluids , and the resulting equations are similar to those of the stiff fluid case . nonetheless , the numerical methods of this paper are not adequate to treat the case of non - stiff fluids . that is because in non - stiff fluids shock waves form , while the numerical methods of the present paper are appropriate for smooth solutions . a shock capturing method would be appropriate to treat the non - stiff fluid case . this work was partially supported by a grant from the national science and engineering research council of canada and by nsf grant phy-0456655 to oakland university .

numerical simulations of the approach to the singularity in spacetimes with stiff fluid matter are presented here . the spacetimes examined have no symmetries and can be regarded as representing the general behavior of singularities in the presence of such matter . it is found that the singularity is spacelike and that as it is approached , the spacetime dynamics becomes local and non - oscillatory .

there is an on - going research effort to identify the quantum features responsible for the computational advantage of quantum over classical computers . one way of doing that is to propose restricted quantum scenarios which can be efficiently simulated on a classical computer , and then add further resources that provably enable universal quantum computation . this classical - to - quantum transition in computational power happens , for example , when we add entangling gates to the set of all single - qubit unitaries or when we add a generic gate to the clifford group of unitaries . another motivation for this approach is the possibility of identifying alternative implementations of quantum computers , which may be more practical , versatile or especially suited to a given physical system . here we investigate the transition from classical to quantum computational power in the context of matchgates , a group of two - qubit gates that were proposed in graph - theoretical terms by valiant in 2002 @xcite . matchgates acting only on nearest - neighbors on a 1d chain of qubits are classically simulatable , a fact that was traced back to their equivalence to a system of non - interacting fermions via the jordan - wigner transformation @xcite . interestingly , they allow for universal quantum computation if next - nearest neighbor matchgate interactions are possible , or by the equivalent use of the swap gate @xcite or other non - matchgate unitaries @xcite . in this paper we ask what happens when matchgates act on nearest - neighboring qubits arranged in geometries other than the linear chain . we prove that there are many possible interaction geometries which enable matchgates to do universal quantum computation , ranging from near - trivial modifications of the chain to quite different graph families , such as star graphs and binary trees . this also partially answers the question of whether the classical simulability of nearest - neighbor matchgates holds beyond the linear chain , an open question up until now ( due , in part , to the fact that the jordan - wigner transformation can not be trivially generalized to nonlinear geometries ) . matchgates arise naturally from interactions in various physical systems , especially in the form of the much studied anisotropic heisenberg ( or xy ) interaction @xcite , which indicates that the geometrical arrangements we propose may be suitable for practical implementations of quantum computers . let @xmath0 denote the 2-qubit gate that acts as unitaries @xmath1 and @xmath2 , respectively , on the even and odd parity subspaces of the 2-qubit hilbert space : @xmath3 if it satisfies the additional constraint that det@xmath1 = det@xmath2 , @xmath0 is a _ matchgate_. valiant introduced matchgates in graph - theoretical terms and provided an explicit algorithm for efficiently simulating matchgates between nearest - neighboring qubits on a linear chain @xcite . curiously , this theoretical construction was later shown to be exactly equivalent to the simulation of non - interacting fermions ; one problem is mapped onto the other via the jordan - wigner transformation @xcite . in 2008 jozsa and miyake complemented this simulability result with the missing element for universal quantum computation : the swap gate , or alternatively the possibility of acting with matchgates between next - nearest - neighbors on the linear chain @xcite . while their main result required encoding each logical qubit into 4 physical qubits , a more economical 2-to-1 encoding was also presented , but which required matchgate interactions between third neighbors . these results can alternatively be stated in terms of the geometrical arrangement of the qubits . remark that nearest- and next - nearest neighbors of the 1d chain can be mapped into nearest - neighbors in the triangular ladder " graph of fig . [ triangladder ] . thus , as was already implicit in previous works @xcite , the computational power of nearest - neighbor matchgates jumps from ( sub-)classical @xcite to quantum universal by rearranging the qubits of the linear chain to form a triangular ladder . in what follows we identify many other graph families that also allow for universal computation with matchgates acting only between nearest - neighbors , including much simpler alternatives to the triangular ladder . we need first to develop a couple of tools . the swap gate [ @xmath4 is parity - preserving but is not a matchgate , as it does not satisfy the determinant condition . this is why the connectivity restrictions are so important quantum information is not free to move around if all we have is matchgates . there is , however , a matchgate which is similar to the swap , which is the fermionic - swap ( f - swap ) : @xmath5 it can not be used to swap the states of two arbitrary qubits , as the minus sign induced in the @xmath6 state can have an entangling effect ( the f - swap is actually a perfect entangler @xcite ) . if , however , we know for certain that one of the input qubits is in the @xmath7 state , then the f - swap acts exactly as the swap , a trick which was already exploited in @xcite with this exact purpose . given the simulability of nearest - neighbor matchgates on the 1d chain , this f - swap trick clearly can not be used to replace next - nearest neighbor interactions . however , if we modify the geometry by introducing a t structure on the chain ( see fig . [ figt]-a ) , we can initialize the appended ancilla in the @xmath7 state and use it to circumvent the need for next - nearest neighbor interactions . to implement any matchgate @xmath8 between qubits @xmath9 and @xmath10 of fig . [ figt]-a , we can apply the sequence : + @xmath11 } \otimes i_{a } = f_{[a , i ] } f_{[i , i-1 ] } g_{[i , i+1 ] } f_{[i , i-1 ] } f_{[a , i]},\ ] ] where @xmath12 is a shorthand for the f - swap and subscripts represent the pair of qubits on which the gate acts , as labeled in fig . [ figt]-a . we see that the f - swap and @xmath7 ancilla effectively simulate a next - nearest neighbor interaction by temporarily `` hiding '' the information of qubit @xmath13 in the appended qubit . we dub this use of the f - swap trick on the t structure a f - swap gadget " . if the states of all qubits can be selectively hidden " in ancillas , all next - nearest neighbor interactions become possible and we achieve universal quantum computation with matchgates only , by the result of jozsa and miyake @xcite . this can be done by introducing multiple t structures on the chain , resulting in the `` hair comb '' graph of fig . [ haircomb ] . furthermore , a trivial extension of the sequence of eq . ( [ swapgadget ] ) enables us to interact qubits which were originally third neighbors , which means we can use the more economical 2-to-1 encoding of @xcite . this is our first result of a graph for universal quantum computation with matchgates . a quick resource count shows that the protocol described enables universal computation using @xmath14 additional f - swaps for each swap and the same number of qubits as the encoded quantum circuit of @xcite , in a simpler graph than the triangular ladder of fig . [ triangladder ] . an interesting alternative demonstration of this result can be given as follows . a standard universal set for quantum computing consists of single - qubit @xmath15-rotations , the hadamard ( @xmath16 ) gate and any two - qubit entangling gate @xcite . as noted in @xcite , matchgates include all single - qubit @xmath15-rotations and many perfect entanglers , which means that matchgates become universal when supplemented by @xmath16 . we now propose a scheme to implement the hadamard @xmath16 gate with matchgates only , based on a simple observation : @xmath17 since @xmath18 is a matchgate , this means that initializing ancilla qubits in the @xmath19 state can replace the need for @xmath16 gates . this clearly can not be used for universal computation on the 1d chain , as in this geometry we can not arrange the required @xmath19 ancillas so as to apply @xmath16 wherever necessary . however , as shown in fig . [ figt]-b , we can again modify the geometry and introduce t structures where appended @xmath19 ancillas effectively apply a @xmath16 gate using the matchgate sequence of eq . ( [ hgadget ] ) . we dub this use of the @xmath18 gate on the t structure an `` h - gadget '' , see fig . [ figt]-b . by repeating this structure at every chain qubit we can implement the @xmath16 gate on any of them , again enabling universal quantum computation with nearest - neighbor matchgates on the hair comb graph of fig . [ haircomb ] . resource - wise , this scheme requires as many gates as the original quantum circuit and twice as many qubits , and does not require encoding as the f - swap gadget scheme does . + + + we can extend these results by noticing that , in both cases , the ancilla s state is left unaltered by the gadgets [ cf . ( [ swapgadget ] ) and ( [ hgadget ] ) ] . physically , this means that some computational qubits can share the same ancilla , going as far as the wheel graph , where a single ancilla is connected to every qubit on the cycle ( see fig . [ examples]-f ) . note that the ancillas used in h - gadgets never get entangled with other qubits , and so can be prepared , used and discarded on the fly if necessary . as we have seen , the `` hair comb '' and wheel graphs allow efficient schemes for universal computation using matchgates only . a large number of graphs which arise naturally in physical systems can be trivially shown to contain those graphs as subgraphs , such as all 2d regular lattices common in solid state physics , and all demi- , semi- and regular tessellations @xcite . however , as we show now , there are strikingly simpler graphs which are also universal for quantum computation if we allow for a larger ( but still polynomial ) overhead in resources . consider first a modification of the cycle graph of @xmath20 vertices @xmath21 , where a single additional vertex is appended to any chosen vertex @xmath13 of the cycle ( see fig . [ examples]-b ) . locally , this appended vertex is equivalent to the t structure of fig . [ figt ] , which means we can use the h - gadget on it , as before . notice also that if we assign one qubit of the cycle as a @xmath7 ancilla , we can use the f - swap trick to move it freely around the cycle . each complete clockwise cycle of the ancilla shifts the state of all other qubits by one step in the counter - clockwise direction ( and vice - versa ) . by f - swapping the ancilla around a sufficient number of times , we can place any qubit on position @xmath13 , where it can undergo an @xmath16 gate via our h - gadget . as before , this allows for universal computation , since the overhead in resources amounts to 2 additional qubits and at most @xmath22 f - swap gates for every @xmath16 gate in the original circuit . this also proves the universality of any graph family with a sufficiently large cycle ( i.e. one that grows polynomially with the size of the graph ) , with the obvious exception of the cycle graph itself . together with the previous results concerning the t structure , this cycle result provides a powerful toolbox for demonstrating the universality of more general families of graphs . for instance , it is easy to show that any graph which contains a polynomially long path where every vertex has degree greater than @xmath23 is universal . this becomes clear by recognizing that every vertex in this long path is either part of a cycle or of a t structure , and our previous results can be combined to provide a universal scheme . notice that these tools may not be sufficient to decide whether an arbitrary graph is universal , as it is np - hard to find the longest path or cycle in a general graph @xcite . nevertheless , they still contemplate any graph family which is known to have a polynomially long path . let us now consider a very slight deviation from the linear chain : we connect a single extra vertex to the central chain vertex , as in fig . [ examples]-d . we can assign the first half of the vertices of the chain as computational , the rest of the chain as @xmath7 states and the appended vertex as a @xmath19 state so as to apply the h - gadget on the central qubit . by using the f - swap trick we can move the state of the computational qubits back and forth , placing any chosen qubit state at the h - gadget site . this results in universal quantum computation with an overhead of at most @xmath24 f - swaps per @xmath16 gate . the scheme , as described , works as long as the extra vertex is sufficiently far away from the endpoints of the chain . if the vertex is logarithmically close to one of the endpoints , the number of qubit states that can be placed at the h - gadget site is logarithmic , and thus insufficient . however , in the appendix we show an alternative universal scheme that works with the extra vertex placed at any point ( with the natural exception of the endpoints ) , at the cost of using a 2-to-1 encoding for the logical qubits . it is surprising that such small deviations from the linear chain already result in universal quantum computation . starting with the chain , it is sufficient to either add a single edge ( creating a cycle ) or append a single ancilla qubit - which can even be just one vertex away from the endpoint . this is similar in spirit to a result in the context of quantum control theory @xcite , where it is shown that , if all neighboring qubits in the linear chain interact with each other via a specific background ( hence uncontrollable ) two - qubit interaction , it suffices to have full control of only the two first qubits of the chain . fast , arbitrary gates on the first two qubits are enough to control the state of the whole chain , driving it to do universal computation . all graph families we have proven so far to be universal for matchgate quantum computation use a long path as a `` backbone '' for the computation , and consist of progressively small deviations from the linear chain . our tools can also be used to prove similar results for a number of graph families which differ significantly from the chain . take the complete binary tree @xcite with @xmath20 leaves , for which the longest path is of size @xmath25 . by assigning the leaves as computational qubits and filling the branches with @xmath7 ancillas , we can use f - swap to move the states of any pair of computational qubits together , interact them and return to the original configuration . this scheme implements each computational matchgate at a cost of a logarithmic number of f - swap gates . it is clear that any graph family where a polynomial - sized set of vertices can be connected to all other vertices in the set by a path of @xmath7 ancilla qubits will be universal for matchgate quantum computation . an interesting , extremal example is the star graph ( see fig . [ examples]-e ) , where the only edges are those between a central vertex and all others . fig . [ examples ] displays various qualitatively different examples of graph families we have proven to be universal for quantum computation using nearest - neighbor matchgates only . in each of these graphs we mark some vertices as @xmath7 or @xmath19 ancillas to highlight one possible universal scheme . for what follows it is important to point out that , while we used the h - gadget in several cases in the interest of displaying economical protocols , it is not strictly necessary in order to demonstrate universality in any situation we have considered . the f - swap gadget can replace the h - gadget on any geometry with only a polynomial overhead in space and time due respectively to the use of encoding and additional f - swap gates . our results will be experimentally relevant in any situation where matchgate interactions arise naturally . as is well - known , the group of matchgates is generated by the set of two - qubit hamiltonians : @xmath26 @xcite . as a practical example , let us consider the much - studied anisotropic heisenberg hamiltonian @xmath27 @xcite . it was proven in @xcite that the matchgates generated by this hamiltonian are universal for quantum computation when allowed to act on next - nearest neighbors on the chain , or equivalently between nearest - neighbors on the triangular ladder of fig . [ triangladder ] . now let us write the f - swap gate in a form that explicits the underlying interactions : @xmath28 \textrm{exp } \left [ i \frac{\pi}{4 } ( xx + yy ) \right].\ ] ] we see that besides the @xmath27 interaction , the f - swap gate also requires single - qubit @xmath15 rotations . this is a possibility in a number of quantum computer implementations , such as cavity qed with atoms @xcite or quantum dots @xcite , and electrons in liquid helium @xcite . given the result of @xcite , our work suggests multiple choices of interaction geometries that may simplify the design of universal quantum computers using these systems . we have also described an alternative matchgate quantum computing scheme that uses h - gadgets instead of the f - swap trick . one advantage of this alternative is that the required @xmath19 ancillas never get entangled with the other qubits , and so can be replaced at will between uses or may even consist of a single , recyclable moving ancillary qubit . we note that the @xmath18 gate can not be decomposed in terms of the same interactions as the f - swap ; it would be interesting to identify a physical implementation where it occurs naturally . in summary , we have proven that nearest - neighbor matchgates are universal for quantum computation in very diverse geometrical settings : on a graph with a large enough cycle , on the star graph , and on a chain with a single appended vertex , for example . the difference between this last case and the simulatable linear chain is minimal , as the single extra qubit may remain in the @xmath19 state during the computation , never entangling with the chain qubits . as a consequence , now we know that it is not possible to efficiently simulate matchgates between nearest - neighbors in all these graph families . it would be interesting if one could find graph families where matchgates are neither simulatable nor universal for quantum computation , an intermediate case of computing power that has drawn much recent interest @xcite . as we have seen , useful sets of matchgates can be generated with the @xmath27 hamiltonian supplemented with single - qubit @xmath15 rotations , present naturally in systems such as cavity qed with quantum dots and atoms , and electrons in liquid helium . our results then suggest different architectures that could enable universal quantum computation in these systems . we leave as an open question whether our tools can be adapted to obtain new architectures where only a single interaction is used ( as in @xcite and @xcite ) . finally we point out that , by applying the jordan - wigner transformation on the 1d chain , one can show that nearest - neighbor matchgates correspond to noninteracting fermions , while matchgates between more distant qubits translate into fermionic interactions @xcite . as our results show the need for only very small deviations from the linear chain , it would be interesting to investigate the implications for proposals for quantum computation with fermions @xcite . in this appendix we show how to use codification and the f - swap gate to achieve universal computation with matchgates on the chain with an appended vertex of fig . [ examples]-d , even if the appended vertex is placed near the chain endpoints . for this , we need to encode each logical qubit into the even parity subspace of two physical qubits as done in @xcite : @xmath29 where subscript @xmath30 denotes a logical qubit . let @xmath31 and @xmath32 represent the arbitrary states of a physical and a logical qubit , respectively . then , it is easy to check that @xmath33 } f_{[2,3 ] } { \left| \psi \right > } { \left| \phi \right>}_l = { \left| \phi \right>}_l { \left| \psi \right>},\ ] ] where @xmath34}$ ] denotes the f - swap acting on qubits @xmath13 and @xmath35 . that is , consecutive applications of the f - swap can move the state of an arbitrary qubit `` through '' a logical qubit . this only works if a complete logical qubit is traversed at a time . the reason behind this is that the f - swap gate will either act as the swap ( if the logical qubit is in the @xmath36 state ) or , if it induces a minus sign , it does so twice ( if the logical qubit is in the @xmath6 state ) . thus , the f - swap can be used to move blocks of two physical qubits around , as long as they comprise the same logical qubit . now consider the universal set constructed in @xcite . a logical single - qubit gate @xmath1 is implemented by the matchgate @xmath37 acting on the two physical qubits that form a logical qubit . a logical entangling gate can be implemented by the sequence : @xmath38 where the first logical qubit is encoded in physical qubits @xmath39 and @xmath23 , and the second logical qubit is encoded in physical qubits @xmath40 and @xmath14 . all gates in the above equation are between qubits @xmath23 and @xmath40 , and this @xmath41}$ ] gate induces an effective @xmath42 gate between the encoded qubits . this can not be implemented in the linear chain with only matchgates because of the swap gate in eq . ( [ controlz ] ) . however , as mentioned in section iv of @xcite , this swap gate can be decomposed in terms of matchgates and hadamard gates on both qubits @xmath23 and @xmath40 . it is clear that we can adapt this result to our context using the tools developed in the main text . suppose that the qubits are aligned on a linear chain , ordered such that every pair @xmath43 comprises logical qubit @xmath13 . since logical single - qubit gates are easy to implement with matchgates , all that is necessary is to implement a logical @xmath42 gate between the two logical qubits at the chain s end , which involve only physical qubits @xmath39 to @xmath14 . if the computation being performed requires a @xmath42 gate between another pair of logical qubits , we simply use the trick of eq . ( [ logicalswap ] ) to swap their state to the endpoint . as shown in @xcite , the logical @xmath42 can be implemented by a physical @xmath42 between any pair consisting of one physical qubit from each logical qubit . by the previous discussion and section iv of @xcite , this reduces to implementing the @xmath16 gate on both these physical qubits . to achieve that , consider the configuration of fig . [ figappend ] , where we appended two ancilla qubits , one in the @xmath7 and one in the @xmath19 state , to the endpoint of the chain . assume w.l.o.g . that the logical qubits we wish to act with the @xmath42 on already occupy positions @xmath44 and @xmath45 , labeled as in fig . [ figappend ] . the scheme to implement the @xmath42 proceeds as follows . using two consecutive f - swaps , swap the state of physical qubit @xmath40 across the first logical qubit ( i.e. to position @xmath39 ) . at this point , positions @xmath39 and @xmath23 are each occupied by one component of a different logical qubit . now use the f - swap trick described in the main text first to swap pair @xmath46 and then pair @xmath47 . this places the @xmath19 ancilla adjacent to the two qubits we wish to apply the @xmath16 on . thus , by repeating this process back and forth we can alternatively implement a matchgate between these two physical qubits or a @xmath16 gate on each of them . consequently , by the result of @xcite , this effectively allows us to implement an entangling gate between the two logical qubits . notice that , after application of the @xmath16 gate , the physical qubits temporarily leave the encoded space . at this point eq . ( [ logicalswap ] ) no longer applies , and any swapping must be made with the aid of the @xmath7 ancilla , as done throughout the main text . only at the end of the sequence of eq . ( [ controlz ] ) do the qubits return to the encoded space and the trick of eq . ( [ logicalswap ] ) can be used to return the logical qubits to their original positions . the scheme described above allows us to implement a logical entangling gate between the first two logical qubits and , by extension , between any pair of logical qubits throughout the circuit . this shows that the 1d chain with a single vertex appended to the second chain vertex is universal for quantum computation with matchgates . in fact , by the previous reasoning it is easy to see that this extra vertex can be appended absolutely anywhere , with the exception of the chain endpoints , completing the demonstration for the claim made in the main text .

matchgates are a group of two - qubit gates associated with free fermions . they are classically simulatable if restricted to act between nearest neighbors on a one - dimensional chain , but become universal for quantum computation with longer - range interactions . we describe various alternative geometries with nearest - neighbor interactions that result in universal quantum computation with matchgates only , including subtle departures from the chain . our results pave the way for new quantum computer architectures that rely solely on the simple interactions associated with matchgates .

zoon 's balanitis or balanitis circumscripta plasmacellularis is a benign chronic disease of unknown origin . zoon 's balanitis , unlike some other inflammatory penile dermatoses , is generally not thought to be a precursor for neoplasia . we herein report the case of an uncircumcised man , who developed clinically and histopathologically evident squamous cell carcinoma of the penis in an area affected by zoon 's balanitis . a 71-year - old uncircumcised man presented with a 3-month history of extremely painful genital sores associated with swollen foreskin and dysuria , not preceded by any flu - like symptoms . the patient reported that he has suffered from zoon 's balanitis for 12 years , confirmed by a histopathological examination . he treated the condition with topical corticosteroids with relative improvement and paid periodic visits for 7 years ; after that he stopped performing any follow - ups . clinical examination revealed a well - demarcated , highly indurated , glistening erythematous plaque ( about 3 cm in diameter ) on the glans and adjacent preputial mucosa . a 3-mm punch biopsy of the glans was performed showing typical features of a moderately differentiated squamous cell carcinoma ( nests of atypical cells with abundant eosinophilic cytoplasm and large vesicular nucleus ) ( fig . zoon 's balanitis is characterized by a solitary red - orange plaque of the glans and prepuce . although the etiology is unknown , different factors have been reported to be involved in its genesis ( local infections , poor hygiene , heat , friction , and constant rubbing ) . histopathologic examination demonstrate an inflammatory infiltrate of predominantly plasma cells , atrophy of epidermis , spongiosis , tortuous dermal blood vessels , and exocytosis of inflammatory cells [ 2 , 3 ] . it is generally considered to be a benign condition , and its association with malignancies has been rarely reported . in 1999 , a case of penis carcinoma arising in a patient with zoon 's balanitis was described by joshi , implying that this inflammatory lesion could be a premalignant condition or could contribute to the development of squamous cell carcinoma . after this report , the hypothesis that zoon 's balanitis may be followed by penile carcinoma or premalignant lesions started to arise . in 2001 , bunker claimed that there were zoonoid changes in clinical and histological features in some cases of lichen sclerosus , lichen planus , bowenoid papulosis and penile cancer . these zoonoid changes could suggest that zoon 's balanitis per se is a premalignant condition . recently , starritt and lee reported a case of erythroplasia of queyrat of the glans on a background of zoon 's plasma cell balanitis . the hypothesis of the possible association between zoon 's balanitis and penile cancer could also be linked to the concept of inflammation as a cofactor in carcinogenesis . in 1863 , virchow noted a connection between inflammation and cancer and sustained that this link may have implications for cancer prevention and treatment . therefore , prevention of penis carcinoma is possible , including early detection and relative treatment of risk factors ( phimosis , inflammatory conditions , multiple sexual partners , and hpv infections ) and precancerous lesions [ 9 , 10 ] . this case highlights the importance of frequent follow - ups for zoon 's balanitis ; topical treatment , such as corticosteroids and calcineurin inhibitors [ 4 , 5 , 7 ] , may be important to prevent the development of a secondary carcinoma . in case of resistance to topical treatments , circumcision should be recommended because it could be curative and also protective against penile carcinoma .

zoon 's balanitis or balanitis circumscripta plasmacellularis is a chronic disease of unknown origin . this condition usually manifests in middle - aged or elderly uncircumcised men . although of unknown etiology , different factors have been reported to be involved in its genesis ( local infections , poor hygiene , heat , friction , and constant rubbing ) . it is generally considered to be a benign condition , and its association with malignancies has been rarely reported . we report the case of an uncircumcised man , who developed clinically and histopathologically evident squamous cell carcinoma of the penis in an area affected by zoon 's balanitis .

SECTION 1. CONSOLIDATION OF LIFE INSURANCE COMPANIES WITH OTHER COMPANIES PERMITTED. (a) In General.--Section 1504(b) of the Internal Revenue Code of 1986 (defining includible corporation) is amended by striking paragraph (2) and by redesignating paragraphs (3) through (8) as paragraphs (2) through (7), respectively. (b) Conforming Amendments.-- (1) Section 1503 of the Internal Revenue Code of 1986 is amended by striking subsection (c) (relating to special rule for application of certain losses against income of insurance companies taxed under section 801) and by redesignating subsections (d), (e), and (f) as subsections (b), (c), and (d), respectively. (2) Section 1504 of such Code is amended by striking subsection (c) and by redesignating subsections (d), (e), and (f) as subsections (c), (d), and (e), respectively. (3) Section 243(b)(2)(A) of such Code is amended by striking ``sections 1504(b)(2), 1504(b)(4), and 1504(c)'' and inserting ``section 1504(b)(3)''. (4) Section 805(a)(4)(E) of such Code is amended by striking ``1504(b)(3)'' and inserting ``1504(b)(2)''. (5) Section 818(e)(1) of such Code is amended to read as follows: ``(1) Items of companies other than insurance companies.-- If an affiliated group includes members which are and which are not life insurance companies, all items of the members of such group which are not life insurance companies shall not be taken into account in determining the amount of the tentative LICTI of members of such group which are life insurance companies.''. (6) Section 832(b)(5)(D)(ii)(II) of such Code is amended by striking ``1504(b)(3)'' and inserting ``1504(b)(2)''. (7) Section 864(e)(5)(A) of such Code is amended by striking ``paragraph (4)'' and inserting ``paragraph (3)''. (8) Section 936(i)(5)(A) of such Code is amended by striking ``section 1504(b)(3) or (4)'' and inserting ``section 1504(b)(2) or (3)''. (9) Section 952(c)(1)(B)(vii)(II) of such Code is amended by striking ``1504(b)(3)'' and inserting ``1504(b)(2)''. (10) Section 953(d)(3) of such Code is amended by striking ``1503(d)'' and inserting ``1503(c)''. (11) Section 954(h)(4)(F)(ii) of such Code is amended by striking ``1504(b)(3)'' and inserting ``1504(b)(2)''. (12) Section 6166(b)(10)(B)(ii)(V) of such Code is amended by striking ``1504(b)(3)'' and inserting ``1504(b)(2)''. (c) Effective Date.--The amendments made by this section shall apply to taxable years beginning after December 31, 2003. SEC. 2. PHASE-IN OF APPLICATION OF CERTAIN LOSSES AGAINST INCOME OF INSURANCE COMPANIES. (a) Phase-in.-- (1) In general.--For taxable years beginning after December 31, 2003, and before January 1, 2010, if-- (A) an affiliated group includes 1 or more domestic insurance companies subject to tax under section 801 of the Internal Revenue Code of 1986, (B) the common parent of such group has not elected under subsection (b) to treat all such insurance companies as corporations which are not includible corporations, and (C) the consolidated taxable income of the members of the group not taxed under such section 801 results in a consolidated net operating loss for such taxable year, then, under regulations prescribed by the Secretary of the Treasury or his delegate, the amount of such loss which cannot be absorbed in the applicable carryback periods against the taxable income of such members not taxed under such section 801 shall be taken into account in determining the consolidated taxable income of the affiliated group for such taxable year to the extent of the applicable percentage of such loss or the applicable percentage of the taxable income of the members taxed under such section 801, whichever is less. The unused portion of such loss shall be available as a carryover, subject to the same limitations (applicable to the sum of the loss for the carryover year and the loss (or losses) carried over to such year), in applicable carryover years. (2) Applicable percentage.--For purposes of paragraph (1), the applicable percentage shall be determined in accordance with the following table: The applicable For taxable years beginning in: percentage is: 2004................................................... 40 2005................................................... 50 2006................................................... 60 2007................................................... 70 2008................................................... 80 2009................................................... 90. (b) Election for Pre-2010 Years of Groups With Insurance Companies.--For taxable years beginning after December 31, 2003, and before January 1, 2010, the common parent of an affiliated group (determined without regard to section 1504(b)(2) of the Internal Revenue Code of 1986 as in effect on the day before the date of enactment of this Act) which includes 1 or more domestic insurance companies subject to tax under section 801 of such Code may elect to treat all such insurance companies as corporations which are not includible corporations within the meaning of subsection (b) of section 1504 of such Code, if, as of the date of enactment of this section-- (1) such affiliated group included 1 or more insurance companies subject to tax under section 801 of such Code, and (2) no additional election was in effect under section 1504(c)(2) of such Code (as in effect on the day before the date of the enactment of this Act). (c) No Carryback Before January 1, 2004.--To the extent that a consolidated net operating loss is allowed or increased by reason of this section or the amendments made by this Act, such loss may not be carried back to a taxable year beginning before January 1, 2004. (d) Nontermination of Group.--No affiliated group shall terminate solely as a result of this section or the amendments made by this Act. (e) Subsidiary Stock Basis Adjustments.--A member corporation's basis in the stock of a subsidiary corporation shall be adjusted upon consolidation to reflect the preconsolidation income, gain, deduction, loss, distributions, and other relevant amounts during a period when such corporations were members of an affiliated group (determined without regard to section 1504(b)(2) of the Internal Revenue Code of 1986 as in effect on the day before the date of enactment of this Act) but were not included in a consolidated return of such group by operation of section 1504(c)(2)(A) of such Code (as in effect on the day before the date of the enactment of this Act) or by reason of the election allowed under subsection (b). (f) Waiver of 5-Year Waiting Period.--An automatic waiver from the 5-year waiting period for reconsolidation provided in section 1504(a)(3) of the Internal Revenue Code of 1986 shall be granted to any corporation which was previously an includible corporation but was subsequently deemed a nonincludible corporation as a result of becoming a subsidiary of a corporation which was not an includible corporation solely by operation of section 1504(c)(2) of such Code (as in effect on the day before the date of enactment of this Act), subject to such conditions as the Secretary may prescribe.

Amends the Internal Revenue Code to include life insurance companies as an "includible corporation" for purposes of filing consolidated tax returns.Permits an affiliated group which includes at least one domestic insurance company that elects to file a consolidated return rather than pay tax under certain life insurance provisions to use a phased-in percentage of insurance company net operating loss in determining its own taxable income. (Permits unused loss carryover.) Provides for: (1) subsidiary stock basis adjustment; and (2) waiver of the five-year reconsolidation waiting period for certain formerly includible corporations which became nonincludible as a result of becoming a subsidiary of a nonincludible life insurance company.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Drug-Free Workplace Act of 1998''. SEC. 2. FINDINGS; PURPOSES. (a) Findings.--Congress finds that-- (1) 74 percent of adults who use illegal drugs are employed; (2) small business concerns employ over 50 percent of the Nation's workforce; (3) in more than 88 percent of families with children under the age of 18, at least 1 parent is employed; and (4) employees who use and abuse addictive substances increase costs for businesses and risk the health and safety of all employees because-- (A) absenteeism is 66 percent higher among drug users than individuals who do not use drugs; (B) health benefit utilization is 300 percent higher among drug users than individuals who do not use drugs; (C) 47 percent of workplace accidents are drug- related; (D) disciplinary actions are 90 percent higher among drug users than among individuals who do not use drugs; and (E) employee turnover is significantly higher among drug users than among individuals who do not use drugs. (b) Purposes.--The purposes of this Act are to-- (1) educate small business concerns about the advantages of a drug-free workplace; (2) provide financial incentives and technical assistance to enable small business concerns to create a drug-free workplace; and (3) assist working parents in keeping their children drug- free. SEC. 3. SENSE OF CONGRESS. It is the sense of Congress that-- (1) businesses should adopt drug-free workplace programs; (2) States should consider incentives to encourage businesses to adopt drug-free workplace programs; (3) such incentives may include-- (A) financial incentives, including-- (i) a reduction in workers' compensation premiums; (ii) a reduction in unemployment insurance premiums; and (iii) tax deductions in an amount equal to the amount of expenditures for employee assistance programs, treatment, or drug testing; and (B) other incentives, such as the adoption of liability limitations, as recommended by the President's Commission on Model State Drug Laws. SEC. 4. DRUG-FREE WORKPLACE DEMONSTRATION PROGRAM. The Small Business Act (15 U.S.C. 631 et seq.) is amended-- (1) by redesignating section 32 as section 33; and (2) by inserting after section 31 the following: ``SEC. 32. DRUG-FREE WORKPLACE DEMONSTRATION PROGRAM. ``(a) Definitions.--In this section: ``(1) Drug-free workplace program.--The term `drug-free workplace program' means a program that includes-- ``(A) a written policy, including a clear statement of expectations for workplace behavior, prohibitions against substances in the workplace, and the consequences of violating those expectations and prohibitions; ``(B) alcohol and drug abuse prevention training for a total of not less than 2 hours for each employee, and additional alcohol and drug abuse prevention training for employees who are parents; ``(C) employee drug testing conducted by a drug testing laboratory certified by the Substance Abuse and Mental Health Services Administration, approved by the Department of Health and Human Services under the Clinical Laboratories Improvement Act of 1967 (42 U.S.C. 263a), or approved by the College of American Pathologists, and a review of each positive test result by a licensed medical review officer; ``(D) employee access to an employee assistance program, including assessment, referral, and short-term problem resolution; and ``(E) continuing alcohol and drug abuse prevention assistance. ``(2) Eligible intermediary.--The term `eligible intermediary' means an organization-- ``(A) that is described in paragraph (3) or (6) of section 501(c) of the Internal Revenue Code of 1986 that is exempt from taxation under section 5(a) of such Code, or a program of any such organization; or ``(B) that provides services to any organization described in subparagraph (A); ``(C) that has not less than 2 years of experience in carrying out drug-free workplace programs or in providing assistance and services to small business concerns; ``(D) that has a drug-free workplace policy in effect; ``(E) that is located in a State, the District of Columbia, or a territory of the United States; and ``(F) the purpose of which is-- ``(i) to develop comprehensive drug-free workplace programs or to supply drug-free workplace services; or ``(ii) to provide other forms of assistance and services to small business concerns. ``(3) Employee.--The term `employee' includes any-- ``(A) supervisor; ``(B) manager; ``(C) officer of a small business concern who is active in management of the concern; and ``(D) owner of a small business concern who is active in management of the concern. ``(b) Establishment.--There is established a drug-free workplace demonstration program, under which the Administrator may make grants to, or enter into cooperative agreements or contracts with, eligible intermediaries for the purpose of providing financial and technical assistance to small business concerns seeking to establish a drug-free workplace program. ``(c) Evaluation and Coordination.--Not later than 1 year after the date of enactment of the Drug-Free Workplace Act of 1998, the Administrator, in coordination with the Secretary of Labor, the Secretary of Health and Human Services, and the Director of the Office of National Drug Control Policy, shall-- ``(1) evaluate the drug-free workplace programs established with assistance made available under this section; and ``(2) submit to Congress a report describing the results of the evaluation under paragraph (1). ``(d) Contract Authority.--In carrying out this section, the Administrator may-- ``(1) contract with public and private entities to provide assistance related to carrying out the program under this section; and ``(2) compensate those entities for provision of that assistance. ``(e) Construction.--Nothing in this section may be construed to require an employer who attends a program offered by an intermediary to contract for any service offered by the intermediary. ``(f) Authorization.--There is authorized to be appropriated to carry out this section, $10,000,000 for fiscal year 1999. Amounts made available under this subsection shall remain available until expended.''. SEC. 5. SMALL BUSINESS DEVELOPMENT CENTERS. Section 21(c)(3) of the Small Business Act (15 U.S.C. 648(c)(3)) is amended-- (1) in subparagraph (R), by striking ``and'' at the end; (2) in subparagraph (S), by striking the period at the end and inserting ``; and''; and (3) by adding at the end the following: ``(T) providing information and assistance to small business concerns with respect to establishing drug-free workplace programs (as defined in section 32(a)).''.

Drug-Free Workplace Act of 1998 - Expresses the sense of the Congress that: (1) businesses should adopt drug-free workplace programs; and (2) States should consider incentives to encourage businesses to adopt such programs, such as reductions in workers' compensation or unemployment insurance premiums, tax deductions, or liability limitations. Amends the Small Business Act to establish a drug-free workplace demonstration program, under which the Administrator of the Small Business Administration (SBA) may make grants to, and contracts or cooperative agreements with, eligible intermediaries to provide financial assistance to small businesses seeking to establish such a program. Sets forth intermediary eligibility requirements. Requires such a program to include: (1) a written policy, including prohibitions against substances in the workplace and violation consequences; (2) alcohol and drug abuse prevention training for employees; (3) employee drug testing; (4) employee access to an assistance program; and (5) continuing alcohol and drug abuse prevention assistance. Authorizes appropriations. Requires small business development centers to provide information and assistance to small businesses in developing drug-free workplace programs.

in order to receive an accurate diagnosis and treatment planning , many researchers have used different criteria to determine the anterior - posterior relationship of the jaws . although molar relationship has been used in angel classification , it is clear that canine and molar relationship indicates the anterior - posterior relationship of the jaws when teeth are placed in the accurate position on the dental arch . using plaster models for classification of malocclusion or determination of the jaws relationship , without lateral cephalometric radiograph is not reliable , particularly for patients who have defective dental structures . currently , several types of intracranial plans have been used as reference lines to determine discrepancy of the jaws . the most popular measurement of discrepancy of the jaws in anterior - posterior dimension is a point , nasion , b point ( anb ) angle , which indicates the relationship of apical base of maxilla to mandible . based on the geometric studies ( studies conducted geometrically rather than statistically ) , following factors are able to change anb angle , without any effect on the anterior - posterior relationship of apical bases : rotation of the jaws around anterior cranial base.rotation of the occlusal plane around anterior cranial base , with or without jaws rotation.position of nasion in the sagittal and vertical dimension and the length of anterior cranial base ( s - n).facial height.rotation of s - n plan . rotation of the occlusal plane around anterior cranial base , with or without jaws rotation . position of nasion in the sagittal and vertical dimension and the length of anterior cranial base ( s - n ) . thus , regarding the geometric studies , anb angle can not always indicate anterior - posterior relationship of the jaws accurately . this index is a linear measurement , which is the distance between two perpendicular lines from points a to b to functional occlusal plane . geometric studies have shown that the value of wits appraisal index may be influenced by alteration of functional occlusal plane and vertical distance of points a and b as well as sagittal alteration of points a and b. some researchers have offered linear and angular measurements based on palatal plane . although this plane is constant , with increasing of age , it has variable gradient , so it is difficult to determine normal average . as these indexes are influenced by anatomic landmarks and dental occlusion and regarding to probability of effect of these landmarks on accuracy of evaluations , it is necessary to access an independent index . recently , and angles have been introduced , which are not dependent on cranial landmarks or dental occlusion . therefore , they are reliable indexes in cases that previous indexes such as anb angle and wits appraisal may not be used . angle is a novel method of measurement of skeletal discrepancy between the maxilla and mandible in sagittal plan . this angle uses three anatomic landmarks : point a , point b and mandibular plan : point a : is the deepest point on the midline of the maxilla , which moves from base to alveolar process . point b : is the most anterior part of base of the mandible and the most posterior point of the outer contour of mandibular alveolar process in midline . angle is the angle between ab line and perpendicular line from a to mandibular plan [ figure 1 ] . angle also uses three anatomic landmarks : point a , point b and condylar axis : point c ( condylion ) : is the most posterior - superior point on condylar head of the mandible ( in the present study , c is considered as the center of the condyle ) . angle is the angle between ab line and perpendicular line from point a to cb line [ figure 2 ] . considering ethnical , sexual and growth differences , it is necessary to evaluate normal cephalometric average of every population . the aim of this study was to evaluate and to compare the range of and angles of 6 - 17-year - old children of isfahan who have normal occlusion . this is a descriptive analytical study . in order to conduct this study , archive documents of orthodontic department of isfahan dental school a total of 235 cephalometric radiographs of children , who had no history of orthodontic treatment and also based on 13 following criteria categorized as normal occlusion , were selected : symmetric face.having the whole teeth regarding to age ( lack of primary tooth was acceptable if there was adequate space).normal tooth form , position and size.class i molar relationship for permanent tooth ( class i molar relationship or end to end relationship during mixed dentition or flush terminal plane relationship of second primary teeth [ e ] in cases of incomplete growth of permanent first molar).class i canine relationship.proper overbite up to 3 mm and over jet up to 2 mm.slight or no space between teeth.slight or no dental rotation.slight or no dental crowding.no posterior cross bite.no history of previous orthodontic treatment.no history of orthognathic surgery.no congenital disorder . having the whole teeth regarding to age ( lack of primary tooth was acceptable if there was adequate space ) . class i molar relationship for permanent tooth ( class i molar relationship or end to end relationship during mixed dentition or flush terminal plane relationship of second primary teeth [ e ] in cases of incomplete growth of permanent first molar ) . acetate tracing paper ( dentaurum , germany ) was used for tracing and cephalometric protractor ( 3 m unitek , corporation , monrovia , california , usa ) with accuracy of 1 was used for measurement . anb angle , wits appraisal index , and angles were measured . during measurement , 16 subjects were excluded due to clear inconsistency between anb angle and wits appraisal index . furthermore , 17 subjects were excluded due to failure of determination of condylar center position in order to measure angle . three subjects were excluded due to superimposition of right and left mandibular plan and consequently failure of determination of angle . finally , 199 subjects ( 112 females and 87 males ) participated in this study . correlations of and angles with anb angle and wits appraisal index were determined using pearson correlation coefficient . t - test was used to determine the relationship between gender and and angles and anova was used to evaluate the relationship between age groups and and angles ( p < 0.05 ) . frequency of 6 - 17-year - old children of isfahan with normal occlusion based on age group mean and standard deviation of and angles are illustrated in table 2 . mean and standard deviation of anb angle , wits appraisal , and angles in 6 - 17-year - old children of isfahan with normal occlusion according to t - test , there was a significant difference between the mean of angle and gender . however , there was no significant difference between other angles and gender [ table 3 ] . there was significant differences between the mean of angle and 14 - 17-year - old age group ( p = 0.01 ) while the mean of angle showed a significant difference in age groups of 8 - 10-year - old ( p = 0.02 ) and 14 - 17-year - old ( p = 0.02 ) . comparison mean and standard deviation of anb angle , wits appraisal , and angles in 6 - 17-year - old children of isfahan with normal occlusion based on sex according to spearmen correlation coefficient there was no significant relationship between angle and age ( p = 0.054 ) ( r = 0.138 ) , while there was a direct , significant relationship between angle and age ( r = 0.435 ) . the relationship between values of and angles and anb angle are presented on diagrams 1 and 2 and the relationship between these angles with wits appraisal index is presented on diagrams 3 and 4 . relationship of angle with a point , nasion , b point angle relationship of angle with a point , nasion , b point angle relationship of angle with wits appraisal index relationship of angle with wits appraisal index accurate measurement of anterior - posterior relationship of the jaws has a major importance in orthodontic treatment plan . the well - known criterion to investigate the anterior - posterior relationship of the jaws is anb angle . a common alternative is wits appraisal index , which is not dependent on cranial landmarks or jaws rotation ; however , accurate diagnosis of functional occlusal plane is difficult and it may occur after orthodontic treatments due to alteration of functional occlusal plane rather than alteration of sagittal relationship of the jaws . in order to compensate the deficiency of anb angle and wits appraisal index , baik and ververidou suggested angle . the researchers claimed that angle not only is independent of cranial landmarks and functional occlusal plane , but also it seems that clockwise or counter - clockwise rotation of the jaws has slight influence on this angle . another advantage of angle is that it can be applied in serial evaluation of orthodontics treatment plan and shows changes in sagittal relationship of the jaws related to growth and orthodontic or orthognathic interference . in addition , it can be used as accurate criteria in orthognathic surgery for patients with anterior - posterior and vertical skeletal disorder . however , major disadvantage of this angle is determination of condylar center , which is not always easy . this issue has been similarly experienced in the present study , which 17 subjects were excluded due to lack of clarity of condylar area . in order to obtain accurate measurement of angle , cephalometric radiographs must have high quality , so that the clinician can easily trace posterior border of ramus and determine condylar head position . the advantage of using the center of condyle rather than condylion point is that accurate tracing of condylar contour is not usually easy . as it is illustrate in figure 2 , if real condylar center is point c , but clinician locates it in a circle with a radius of 2 mm , angle is affected less than 1 , which makes its application more acceptable . in the present study , baik and ververidou showed the range of angle 27.5 - 43.5 and 27 - 35 respectively . the difference between these studies is probably due to different sample size , inclusion criteria and demographic features of patients . the mean of angle was 31.7 3.3 in the current study , which is consistent with the results of fattahi et al . suggested angle , which is superior to angle because the determination of mandibular plane is easier and the quality of radiograph does not influence this plane . however , mandibular plane may be defective in some lateral cephalograms due to weak radiographic technique . one of the advantages of angle is that the rotation of the lower jaw from temporomandibular joint area or the rotation of mandibular body does not really influence the angle as a and b points change their position . however , if mandibular plane changes without displacement of a and b points , the angle will be failed . in the present study , the range of angle was 8 - 27 , while fattahi et al . showed 11 - 29 . the mean value of angle was 17.34 3.74 , which is consistent with the results of fattahi et al . according to spearman correlation coefficient there was direct significant , but weak relationship between angle and age ( r = 0.435 ) . as angle increases with the increase of age , it can be suggested that angle is consistent with cephalocaudal gradient of the growth curve . pearson correlation coefficient revealed that there was reverse significant relationship between anb angle and angle ( r = 0.520 ) and also angle ( r = 0.329 ) . as an increase in angle and angle indicated a tendency to class iii and a decrease in anb angle indicates the same tendency , these angles reinforce each other in the classification of the malocclusion . there was also weak and reverse significant relationship between wits appraisal index and angle ( r = 0.412 ) and angle ( r = 0.427 ) . as increase of these angles and a decrease of wits appraisal index ( more negative ) indicate tendency to c1ass iii , both of them reinforce each other in the classification of the malocclusion . biak and ververidou suggested that there is a significant relationship between anb angle and wits appraisal index and angle . according to the present study , there was a direct significant relationship between angle and angle ( r = 0.621 ) . therefore , it can be said that these two angles have consistent validity and can be well used in the determination of anterior - posterior malocclusion . in fact , all linear and angular measurement in lateral radiographies has specific advantages and disadvantages , thus none of the methods can be used merely as an accurate method for diagnosis and treatment plan in orthodontics . although angle and angle are able to diagnosis the anterior - posterior relationship of the jaws and bone disorder , previous cephalometric measurements should not be ignored . based on the findings of the current study , further studies on the sensitivity and specificity of angle and angle in three types of malocclusion and also comparison of these angles with other method of measuring jaw relationship such as the angle of convexity and facial angle are recommended . considering that angle and angle do not have the disadvantages of previous measurements such as anb angle and wits appraisal index for evaluation of anterior - posterior relationship of the jaws , they may be an accurate method for diagnosis of jaw disorders and treatment plan .

background : linear and angular measurements such as a point , nasion , b point ( anb ) angle and wits appraisal index are not accurate enough to evaluate sagittal relationship of the jaws . the aim of this study was to evaluate and compare the range of and angles in 6 - 17-year - old children of isfahan , having normal occlusion.materials and methods : this was an analytical descriptive study . for this study , 235 cephalometric radiographs of patients who did nt receive orthodontics treatments and based on 13 indexes had normal occlusion , were selected . after tracing of cephalograms , anb angle , wits appraisal index , angle ( resulted from the intersection of ab line and perpendicular line from point a to mandibular plane ) and angle ( resulted from the intersection of ab line and perpendicular line from point a on cb line ) were measured . data was analyzed by t - test , anova and pierson - spearman correlation coefficient ( p < 0.05).results : mean value of and angles were 17.34 3.47 and 31.7 3.31 and ranged from 8 - 27 to 21.5 - 39 respectively . according to t - test , there was a significant difference between two sex groups for angle ( p = 0.02 ) ; however , it was not significant for angle . according to spearman correlation coefficient , there was no significant difference between age and angle ; however , angle was directly and significantly related to age ( r = 0.435 ) . there was significant and reverse relationship between and angles with anb angle and wits appraisal index.conclusion: and angles are reliable and can be used to evaluate the anterior - posterior relationship of the jaws .

time series photometry from the kepler k2 mission @xcite has led to the discovery of a number of interesting eclipsing binary systems . a particular example and the subject of this paper is an eccentric orbit binary associated with epic 202062176 @xcite . this star sits at the center of a young cluster of stars embedded in the h ii region sh 2 - 252e , which in turn is one of six young clusters associated with the large , diffuse h ii region , ngc 2174 ( sh 2 - 252 , * ? ? ? * ; * ? ? ? all these clusters have an estimated age of 5 myr or less , consistent with the age of the primary ionizing source , the o6.5 v star hd 42088 @xcite . we analyzed the k2 campaign 0 light curve of epic 202062176 in order to determine the system s orbital elements . however , there are over 100 main sequence and pre - main sequence stars in the embedded cluster surrounding epic 202062176 @xcite . the large k2 c0 photometric aperture actually records the flux of dozens of stars including several relatively bright and close by targets , seen in the @xmath0 and @xmath1 images in figure [ ctio ] . therefore , there is real uncertainty about which star in the vicinity of epic 202062176 is actually the eclipsing binary . in order to solve this problem , we obtained spectra of the three brightest stars within the k2 c0 aperture based on the color - magnitude diagram of these stars , shown in figure [ cmd ] . the names and coordinates of our targets are listed in table [ coord ] . the brightest target in sh 2 - 252e is sh 2 - 252a , an early b - type star that corresponds to epic 202062176 . sh 2 - 252a has been studied in the past using both multi - band photometry and low resolution spectroscopy @xcite . the second brightest target is sh 2 - 252b , a herbig ae star located @xmath2 southwest of sh 2 - 252a @xcite . the third brightest target is a star @xmath3 southeast of sh 2 - 252a , which we call sh 2 - 252c . the a and c components are not clearly resolved in figure [ ctio ] , but the pair is clearly visible in a higher resolution image presented in figure 1 of the paper by @xcite . our observations are described in section [ observations ] . we present our analysis of the k2 c0 light curve in section [ photometry ] and the spectroscopic analysis of sh 2 - 252a , sh 2 - 252b , and sh 2 - 252c in section [ spectroscopy ] . the results are summarized in section [ discussion ] . lcccl sh 2 - 252a & 06:09:52.6 & + 20:30:16.4 & 9.86 & 2mass 06095263 + 2030164 , epic 202062176 , als 17694 + sh 2 - 252b & 06:09:51.7 & + 20:30:06.2 & 12.22 & 2mass 06095168 + 2030061 , hbha 2215 - 05 + sh 2 - 252c & 06:09:52.8 & + 20:30:10.7 & 12.24 & 2mass 06095278 + 2030106 + epic 202062176 was observed in k2 campaign 0 in long - cadence mode . we used the data from 2014 april 22 - 2014 may 27 ( bjd 2456770 - 2456805 ) , because data from the first half of campaign 0 was lost due to a spacecraft pointing issue . we completed our data reduction using pyke tools @xcite . the light curve was extracted from a custom aperture mask , background subtracted , and de - trended . the aperture mask used was a circular mask roughly @xmath4 in diameter and centered on epic 202062176 . we corrected for spacecraft motion artifacts using the kepsff task of @xcite . the reduced light curve for epic 202062176 is shown in top panel of figure [ pulsations ] . we obtained 13 nights of data for sh 2 - 252a using the chiron echelle spectrograph @xcite on the ctio 1.5 m telescope in 2014 november - december . we also obtained one night of data for sh 2 - 252a , sh 2 - 252b and sh 2 - 252c using the astrophysical research consortium echelle spectrograph ( arces , * ? ? ? * ) on the apo 3.5 m telescope on 2016 february 11 . the chiron spectrograph covers 4500 - 8900 at a resolving power of r@xmath527400 . three 900 sec exposures were taken in fiber mode and averaged for each night . a thorium - argon lamp spectrum was taken after each object spectrum for wavelength calibration . these spectra were reduced using the ctio pipeline from yale university @xcite , transformed onto a heliocentric wavelength grid , and continuum normalized . the arces spectrograph covers 3500 - 10600 at a resolving power of r@xmath531500 . one spectrum was obtained for each target in slit mode . the exposure times for sh 2 - 252a , sh 2 - 252b , and sh 2 - 252c were 1800 sec , 3200 sec , and 3800 sec , respectively . a thorium - argon lamp spectrum was taken after each object spectrum for wavelength calibration . these spectra were reduced using standard procedures in iraf , transformed onto a heliocentric wavelength grid , and continuum normalized . the k2 c0 light curve of epic 202062176 exhibits shallow eclipses as well as low amplitude variations , possibly caused by stellar pulsation or rotational modulation of star spots . we used the program period04 @xcite to determine these photometric periods by completing a fourier transform of the eclipse - free light curve . the resulting power spectrum revealed only two strong periods , @xmath6 days and @xmath7 days , as shown in figure [ powerspec ] . we subtracted a model of these periodicities from the observed light curve in order to isolate the eclipses , as shown in the middle panel of figure [ pulsations ] . we folded the k2 c0 light curve based on the orbital period and epoch of primary eclipse found by @xcite , @xmath8 days and @xmath9 bjd 2456775.899 . figure [ foldedlc ] shows the folded light curve . from the eclipse durations and separations , we calculated the eccentricity , @xmath10 , and longitude of periastron , @xmath11 , which are consistent with the values found by @xcite . we then used a light curve synthesis program , eclipsing light curve code ( elc , * ? ? ? * ) , to model the eclipses and determine the orbital parameters of the eclipsing binary . the period , epoch of primary eclipse , eccentricity , and longitude of periastron were held fixed while we varied other parameters , such as the inclination , roche lobe filling factors , and @xmath12 ratio . we also assumed a mass ratio @xmath13 , although the solutions are relatively insensitive to this estimate . table [ elctable ] lists the best - fit parameter estimates , found by visual inspection . figure [ foldedlc ] shows the best - fit elc model . the eclipse depths of the eclipsing binary are only 3 - 4% percent , which implies a relatively low inclination . however , reducing the inclination was not enough to match the observed light curve . by fitting elc models with different third light components , we found that a third light contribution of 90% is needed to dilute accurately the eclipses , i.e. , 90% of the total flux comes from nebular and stellar light from sh 2 - 252e while only 10% comes from the binary itself . however , there is a limited family of solutions due to the direct correlation between inclination and third light contamination : the inclination ranges from @xmath14 for a contamination factor of @xmath15 , to @xmath16 for a contamination factor of @xmath17 . the increase in flux between eclipses ( at phase @xmath18 ) due to tidal distortions provided a lower limit to the inclination and contamination factor , because the models with inclinations lower than @xmath19 and low contamination display a much larger increase in flux than that found in the observed light curve ( figure [ foldedlc ] ) . future observations using higher resolution photometry should be able to reduce the amount of contamination and better determine the inclination of the binary system . ll orbital period @xmath20 ( days ) & 4.354250 + epoch of primary eclipse @xmath21 ( bjd ) & 2456775.8988 + epoch of periastron ( bjd ) & 2456772.2194 + eccentricity @xmath22 & 0.45 + longitude of periastron @xmath23 ( deg ) & 199 + inclination @xmath24 ( deg ) & 86.5 + effective temperature ratio @xmath25 & 0.90 + relative radius of primary @xmath26 & 0.096 + relative radius of secondary @xmath27 & 0.086 + third light contamination ( % ) & 90 + sh 2 - 252a was classified in the past between o8 - b1 v @xcite . to confirm this spectral type , we compared our time - averaged chiron spectrum to the tlusty bstar2006 model spectra of @xcite . because sh 2 - 252a is only a few million years old @xcite , all models have solar abundances . due to reflected continuum light from the surrounding nebula @xcite , all of the absorption lines are shallower in the observed spectrum than in the model spectra . to avoid problems of absolute line strength , we measured the ratios of the equivalent widths of several absorption lines in our observed spectrum and in tlusty models of various effective temperatures ( @xmath12 ) and surface gravities ( @xmath28 ) . we used the temperature - dependent ratios @xmath294640/ @xmath294643 , @xmath294654/ @xmath294568 , and @xmath295696/ @xmath295697 to determine the best - fit @xmath12 , and used the luminosity - dependent ratios @xmath294387/ @xmath294416 , @xmath294552/ @xmath294387 , and @xmath294089/ @xmath294026 to determine the best - fit @xmath28 . we found that sh 2 - 252a has @xmath30 k and @xmath31 , where the errors correspond to the standard deviation of the results from all line ratios . therefore , sh 2 - 252a corresponds to a spectral type of b0.5 v , according to table b.1 in @xcite , which is consistent with past studies . figure [ siiii ] shows the observed triplet @xmath32 as well as a tlusty model for @xmath33 k. we then used this model spectrum to measure the third light contamination of the chiron spectra to be 34% and of the arces spectra to be 12% . because the width of the arces slit ( @xmath34 ) is smaller than the diameter of the chiron fiber ( @xmath35 ) , much less reflected continuum light was able to enter the spectroscopic aperture of arces . figure [ siiii ] also demonstrates how sharp are the absorption lines of sh 2 - 252a . we found the projected rotational velocity ( @xmath36 ) of sh 2 - 252a by first scaling the line depths of the model spectrum to match the depths of the chiron spectrum . we then measured the instrumental broadening of the thar lamp spectra to be 12 km s@xmath37 fwhm and fit the observed line profiles over models of different @xmath36 . we found that @xmath38 km s@xmath37 , i.e. , any projected rotational velocity is too small to measure at the resolving power of our spectra . the spectra of sh 2 - 252a show strong nebular emission lines , such as the balmer series and several forbidden lines , from the diffuse h ii region ( ngc 2174 ) and nebulosity ( sh 2 - 252e ) near sh 2 - 252a . @xcite found that the balmer lines originate from both ngc 2174 and sh 2 - 252e , while the [ ] and [ ] lines originate only from sh 2 - 252e . we measured the equivalent width ( @xmath39 ) of h@xmath40 emission in the spectra of sh 2 - 252a for comparison with that of sh 2 - 252b and sh 2 - 252c , listed in table [ rvtable ] . h@xmath40 was saturated in one or more of the three exposures for each night of chiron observations , so we only used exposures where h@xmath40 is unsaturated . nights when all three exposures are saturated are left blank in the table . this measurement was made using numerical integration across the emission line profile , with the baseline determined by a linear fit between endpoints of the line . sh 2 - 252a is much brighter than sh 2 - 252b or sh 2 - 252c , so the nebular emission lines do not appear as strong relative to the bright continuum of sh 2 - 252a . we measured the radial velocity ( @xmath41 ) of each chiron spectrum using cross - correlation with a tlusty model spectrum of @xmath42 k. we combined the results of multiple echelle orders to calculate the average @xmath41 for each night , listed in table [ rvtable ] . the average radial velocity from all 13 nights is 25.109 @xmath43 0.025 km s@xmath37 . sh 2 - 252a does not show significant radial velocity variations on the orbital timescale of the eclipsing binary , and therefore must not be part of the binary system . the radial velocity of the arces spectrum is @xmath44 km s@xmath37 . even though this spectrum was taken 14 months after the chiron spectra , the radial velocities are very consistent . sh 2 - 252a could be a distant companion to the binary system , but would have an orbital period much longer than our 14 month baseline . ccccrc sh 2 - 252a & 2456980.604 & 24.91 & 0.09 & 2.54 & ctio + sh 2 - 252a & 2456982.656 & 25.04 & 0.08 & 2.40 & ctio + sh 2 - 252a & 2456986.882 & 25.22 & 0.09 & 2.32 & ctio + sh 2 - 252a & 2456987.707 & 25.14 & 0.09 & 2.49 & ctio + sh 2 - 252a & 2456988.704 & 25.14 & 0.10 & & ctio + sh 2 - 252a & 2456990.571 & 25.14 & 0.10 & & ctio + sh 2 - 252a & 2456991.612 & 25.11 & 0.12 & & ctio + sh 2 - 252a & 2456992.871 & 25.13 & 0.09 & & ctio + sh 2 - 252a & 2456994.604 & 25.07 & 0.10 & & ctio + sh 2 - 252a & 2456995.895 & 25.04 & 0.08 & 2.25 & ctio + sh 2 - 252a & 2456997.680 & 24.99 & 0.09 & 2.69 & ctio + sh 2 - 252a & 2457012.859 & 25.09 & 0.11 & & ctio + sh 2 - 252a & 2457013.771 & 25.29 & 0.10 & 2.90 & ctio + sh 2 - 252a & 2457430.670 & 25.18 & 0.24 & 2.81 & apo + + sh 2 - 252b & 2457430.700 & 16.80 & 2.99 & 157.56 & apo + + sh 2 - 252c & 2457430.744 & 17.44 & 1.28 & 80.19 & apo + to investigate whether the eclipsing binary is another star still within the spectroscopic aperture , we searched for hidden spectral features of the binary system using a doppler tomography algorithm @xcite . we first calculated the semi - major axis of the binary system from kepler s third law , based on the orbital period found by @xcite and assuming both components are @xmath45 stars ( @xmath46 ) . combining this with the inclination , eccentricity , and time of periastron from elc , we calculated the velocity semi - amplitude of the binary system . finally , we used the sbcm program @xcite to predict the radial velocity of each component at the time of each chiron observation , using the same systemic velocity as that of sh 2 - 252a . the doppler tomography algorithm then worked to find any observed spectral lines with these radial velocity shifts and created a reconstructed spectrum with these lines . unfortunately , our reconstructed spectrum of the binary star did not show any spectral features , so we conclude that the eclipsing binary is more separated from sh 2 - 252a than the fiber aperture radius , i.e. , more than @xmath47 away . @xcite discovered that sh 2 - 252b is a herbig ae star , based on its broad h@xmath40 emission , infrared flux excess , and high luminosity . our arces spectrum of sh 2 - 252b shows broad balmer and paschen emission lines , as well as narrow nebular emission from ngc 2174 and sh 2 - 252e . h@xmath40 has a double - peaked profile , shown in the top left panel of figure [ balmer ] , indicative of a circumstellar disk . we measured the equivalent width of h@xmath40 in the same manner as described above and found @xmath39 = -158 . note that this equivalent width does include nebular emission components . sh 2 - 252b does not show any strong absorption lines , likely due to dilution from bright circumstellar material @xcite , making spectral classification very difficult . @xcite created an sed from broad - band photometry and measured the balmer jump to determine the spectral type of sh 2 - 252b to be a0 @xmath43 2 subclasses . we instead estimated the johnson @xmath48 , @xmath49 , and @xmath50 colors for sh 2 - 252b based on the intrinsic colors of a b0.5 v star from @xcite and the raw flux values ( @xmath51 ) of sh 2 - 252a and sh 2 - 252b at 4400 , 5500 , 6410 , and 7890 . for example , the equation for the @xmath48 color of sh 2 - 252b is given by @xmath52 where @xmath53 @xcite . this approach assumes that the observations were made with approximately the same air mass and seeing conditions . we estimated the colors of sh 2 - 252b to be @xmath54 , @xmath55 , and @xmath56 , which all match those of an a0 v star @xcite . because sh 2 - 252b does not show absorption lines , we estimated its radial velocity using the paschen emission lines in the near - ir , shown in figure [ paschen ] . we fit a single gaussian to each emission line , and found that the average @xmath41 is 16.8 km s@xmath37 with a standard deviation of 3.0 km s@xmath37 . we then used the sbcm code to predict the radial velocities of the eclipsing binary stars at the time of our arces observation . the predicted radial velocities of two @xmath57 stars in the binary system with the same systemic velocity of sh 2 - 252a are @xmath58 and @xmath59 km s@xmath37 , which does not match the radial velocity of sh 2 - 252b . we conclude that sh 2 - 252b is not a component of the eclipsing binary system . sh 2 - 252c has only been observed in the past as part of the 2mass survey @xcite , but is relatively faint and has poor quality @xmath1 magnitudes . no prior spectroscopic observations or spectral classifications have been made for this star . unfortunately , sh 2 - 252c does not show absorption lines in the blue due to the low signal - to - noise ratio of our spectrum , so we were unable to identify the h & k lines , the g band , or @xmath60 line which could all aid in spectral classification @xcite . the red and near - ir proved more useful . first , there is no evidence of broad hydrogen absorption under the nebular emission , which suggests that sh 2 - 252c is a cooler , lower mass star . second , we were able to identify several , , and absorption lines , as well as possible , , and absorption lines . specifically , @xmath61 , @xmath62 , @xmath63 , @xmath64 , @xmath65 , and the triplet @xmath66 . these absorption lines are likely diluted by reflected continuum light from sh 2 - 252e , as was the case for sh 2 - 252a . however , many of these absorption lines are present in f through m stars , so we could only conclude that sh 2 - 252c is a mid - f or later type star . we also calculated the @xmath48 , @xmath49 , and @xmath50 colors of sh 2 - 252c in the same manner as for sh 2 - 252b . we found @xmath67 , corresponding to a mid - f star , @xmath68 , corresponding to a early k star , and @xmath69 , corresponding to an early k star @xcite . this discrepancy in spectral types implies that sh 2 - 252c has an infrared excess or blue deficient flux . furthermore , we used the raw flux values to estimate @xmath70 for sh 2 - 252c . comparing the @xmath71 magnitudes of sh 2 - 252a and sh 2 - 252c to their @xmath72 magnitudes from 2mass , sh 2 - 252c is overly bright in @xmath72 by almost 2 magnitudes . this suggests that sh 2 - 252c is a pre - main sequence star , which is consistent with the appearance of the and absorption lines . these lines are very narrow compared to the same lines in the sun s spectrum , due to the decreased pressure broadening of a pre - main sequence star relative to a main sequence dwarf . to calculate the radial velocity of sh 2 - 252c , we cross - correlated our arces spectrum with a bluered model spectrum from @xcite . we used a model with @xmath73 k , corresponding to a k2 star and the approximate spectral type of sh 2 - 252c . an example part of the spectrum is shown in figure [ order72 ] , which shows only marginal agreement with the observed spectrum due to the low signal to noise ratio of our spectrum and contamination with emission components in some lines . we found @xmath74 km s@xmath37 for sh 2 - 252c . as described above , the predicted @xmath41 of the eclipsing binary stars at the time of our arces observation are @xmath58 and @xmath59 km s@xmath37 . we do not find any absorption lines with these radial velocities nor do we see any evidence of double lines , which excludes sh 2 - 252c as a possible component of the eclipsing binary system . we conclude that epic 202062176 is not actually the eclipsing binary itself , but its measured flux is contaminated by a nearby binary in the k2 c0 aperture . the eclipses are highly diluted by light from nearby stars and the surrounding nebulosity within the large aperture , with the binary contributing only 10% of the total flux . we also found that the component stars are similar in effective temperature and therefore are likely similar masses . this young , eccentric binary would be an interesting target for studies on apsidal motion due to its young , low mass components and close orbit . assuming @xmath75 , the semi - major axis of the eclipsing binary system is @xmath76 . combining this with the relative radii determined by elc , the individual stellar radii are thus @xmath77 and @xmath78 . the primary and secondary stars are larger than the expected main sequence radius and are likely pre - main sequence stars . the periastron distance of the two stars is @xmath79 , much larger than @xmath80 , suggesting that the two components are completely detached . further work to identify the eclipsing binary could include time series photometry with better spatial resolution than kepler or spectroscopic observations of the other nearby stars . we ruled out the three brightest stars as possible members of the eclipsing binary , so other candidates are the next two brightest stars within the photometric aperture : 2mass 06095246 + 2030029 ( @xmath81 ) and 2mass 06095300 + 2030011 ( @xmath82 ) . these stars are labeled on the color - magnitude diagram in figure [ cmd ] . the remaining nearby stars are very faint ( @xmath83 ) and do not contribute enough light to be probable members of the eclipsing binary system . the other intriguing element of the k2 c0 light curve was the low amplitude variation , with @xmath6 days and @xmath7 days . one explanation is that these variations are caused by pulsations of sh 2 - 252a . the pulsation periods are too long for the @xmath84-mode pulsations of @xmath85 cephei and @xmath86 scuti stars , but the periods are consistent with the @xmath87-mode pulsations of @xmath88 doradus and slowly - pulsating b stars @xcite . however , the spectral type of sh 2 - 252a is much earlier than the usual spectral types of these pulsating stars . a more plausible explanation would be that the observed variations are caused by the rotational modulation of star spots . sh 2 - 252a is not a likely source , because its slow rotation would create variations with much longer periods . on the other hand , these periods are reasonable for the rotation of sh 2 - 252b and sh 2 - 252c . even though we excluded sh 2 - 252a ( epic 202062176 ) , sh 2 - 252b , and sh 2 - 252c as components of the eclipsing binary system , these stars are still very interesting . sh 2 - 252a is a b0.5 v star with remarkably sharp absorption lines . we found @xmath89 km s@xmath37 , which is very slow even for a low inclination . this is very surprising for such a young , early type star that would have been born with high angular momentum from the molecular cloud . it is possible that the low @xmath90 is due to a small inclination , but the probability is low that we view the star with a pole - on orientation . alternatively , sh 2 - 252a could have been spun down by a magnetic field , the case for many early - type slow rotators . for example , @xcite found that three of the four hottest b stars with magnetic fields are very sharp - lined . one of these is @xmath91 sco , a well studied magnetic b0.2 v star with @xmath92 km s@xmath37 @xcite , similar to sh 2 - 252a . furthermore , about 10% of b stars have magnetic fields @xcite , and young massive stars are even more likely to have magnetic fields @xcite . therefore , sh 2 - 252a is possibly a magnetic star due to its slow rotation and young age . if it is magnetic , the strong magnetic field required to slow its rotation in only 5 myr would likely be detectable , making sh 2 - 252a a promising target for the study of magnetic o and b stars . the magnetic field of sh 2 - 252a could also have influenced the accretion disk during its formation and even confined the outflow of debris to create the dark dust band seen in figure [ ctio ] . next , sh 2 - 252b is a herbig a0e star with a double - peaked h@xmath40 profile , evidence of a circumstellar disk . sh 2 - 252c is likely a low mass pre - main sequence star due to its ir excess , over - brightness , and possible dilution from circumstellar gas and dust . while we concluded that these stars are not components of the binary system itself , we can not exclude the possibility that they could be a distant third companion to the binary system . nonetheless the eclipsing binary in sh 2 - 252e was clearly born in a dense environment with remarkable neighbors , and further efforts to identify the binary among the cluster stars will help elucidate its role in the early dynamical evolution of the cluster .

we present a photometric and light curve analysis of an eccentric eclipsing binary in the k2 campaign 0 field that resides in sh 2 - 252e , a young star cluster embedded in an h ii region . we describe a spectroscopic investigation of the three brightest stars in the crowded aperture to identify which is the binary system . we find that none of these stars are components of the eclipsing binary system , which must be one of the fainter nearby stars . these bright cluster members all have remarkable spectra : sh 2 - 252a ( epic 202062176 ) is a b0.5 v star with razor sharp absorption lines , sh 2 - 252b is a herbig a0 star with disk - like emission lines , and sh 2 - 252c is a pre - main sequence star with very red color .

statistical systems of many particles have been object of intense analysis for a long time , both from the perspective of physics and mathematics . the study of a particular type of interacting particle systems , the so - called determinantal point processes ( and their cousins , pfaffian processes ) , has been especially fruitful in the past thirty years . this success can be explained both by the ubiquitous character and flexibility of these models ( describing the eigenvalues of several random matrix ensembles , non - intersecting diffusion paths , random growth models , random tilings , to mention a few ) and the introduction of new tools , intrinsically related with the analytic theory of orthogonal polynomials and their generalizations . a common feature of these models is that either the joint probability density , the correlation functions , the normalization constant or the generating function can be expressed as a determinant ( resp . , a pfaffian ) , and the right selection of the functions appearing in these determinants unveils the integrable structure of the underlying processes . another unified property of these models is the possibility to put them in the framework of the so - called log gases , where the particles behave as charges on one or two dimensional sets , subject to the logarithmic interaction . the best known case is the spectrum of some unitary matrix ensembles @xcite , described in terms of classical families of orthogonal polynomials on the real line . their zeros , all real and simple , satisfy an electrostatic model that goes all the way back to stieltjes @xcite , and solve a minimization problem for the associated ( logarithmic ) energy . in other words , the zeros provide an equilibrium configuration on the conducting real line . similar situation occurs for some non - intersecting paths models or for the six - vertex model in statistical mechanics @xcite , to mention some more examples . another classical framework for orthogonal polynomials ( orthogonality on the unit circle ) , developed in the seminal works of szeg @xcite , is connected to the analysis of the ising model @xcite . further immediate generalizations of the problems above oblige us to leave the real line and extend the notion of orthogonality and the associated log gas models to the complex plane . the so - called _ non - hermitian orthogonal polynomials _ appear naturally in approximation theory , as denominators of rational ( e.g. pad ) approximants to analytic functions @xcite , or equivalently , in the study of continued fractions . electrostatic models on a conducting plane are also associated with the polynomial solutions of certain linear differential equations @xcite . recently , non - hermitian orthogonality found its way to areas with a much more `` modern '' flavor , playing the crucial role in the description of the rational solutions to painlev equations @xcite , in theoretical physics @xcite and in numerical analysis @xcite . observe that due to analyticity , there is a certain freedom in the choice of the integration contour for the non - hermitian orthogonal polynomials , which means that the location of their zeros is a priori not clear . as it follows from the fundamental works of nuttall @xcite and stahl @xcite ( see also the survey @xcite ) , the limiting zero counting measure of these polynomials can be characterized in terms of certain max - min problems of the logarithmic potential theory , where the energy is minimized on each compact set , but these minima are maximized over an appropriately chosen class of contours . these questions ( whose simplest example is the chebotarev s problem @xcite about the selection of sets of minimal logarithmic capacity ) are closely related to the free boundary problems in the theory of partial differential equations . motivated by his study of convergence of pad approximants to functions with branch points , stahl @xcite not only proved that the zeros of the associated non - hermitian orthogonal polynomials distribute asymptotically as the equilibrium measure on the set of minimal capacity within the appropriate class ( proving in passing their existence ) , but also characterized these sets in terms of a symmetry property , now known as the _ @xmath1-property_. these ideas were considerably extended by gonchar and rakhmanov @xcite to include the case when the orthogonality weight depends on the degree of the polynomial . the electrostatic model features now a non - trivial external field ( or background potential ) that persists in the asymptotic regime ; in consequence , the notion of the @xmath1-property had to be extended to deal with this external field . the resulting gonchar - rakhmanov - stahl ( or grs ) theory allows to formulate conditional theorems of the form : `` _ _ if _ _ there exists a compact set with the @xmath1-property corresponding to the associated electrostatic model , then the weak limit of the zero counting measures of the related non - hermitian orthogonal polynomials is the equilibrium measure of this set '' . however , the existence of such compact sets is a problem from the geometric function theory , and it usually has to be settled in each concrete situation , basically from scratch . there are very few genuinely general rigorous results in this sense , for instance the most recent one of kuijlaars and silva @xcite settling down the existence for polynomial external fields on the plane , and also the contribution by kamvissis and rakhmanov @xcite which deals with the green potential instead of the logarithmic potential . the notion of the @xmath1-property found also a natural interpretation in the light of the deift - zhou s non - linear steepest descent method for the riemann - hilbert problems @xcite . one of the key steps in the asymptotic analysis is the deformation of the contours , which transforms oscillatory behavior into a non - oscillatory plus exponentially decaying one . this deformation consists in `` opening of lenses '' along the level sets of certain functions ( known as _ @xmath2-functions _ ) . it is precisely the @xmath1-property of these sets which guarantees the exponential decay on all non - relevant contours . the available log gas models on the conducting plane suggest to extend the analysis of the equilibrium distributions ( local energy minima on the prescribed sets ) to the study of saddle points of the logarithmic energy on the plane . this yields the notion of _ critical measures _ , studied systematically in @xcite , following the original ideas in the unpublished manuscript @xcite . the advantage of dealing with saddle points of the energy is the possibility to avoid the complications of the free boundaries , as well as to use variational techniques that go back to the work of lwner and schiffer . one of the main conclusions of @xcite ( see also @xcite ) is the fact that the cauchy transform of any critical measure satisfies ( a.e . on the plane ) a quadratic equation , known as the _ spectral curve _ in the context of random matrix theory . an immediate consequence of this fact is that the support of such a measure is a finite union of analytic curves , all of them being trajectories of the same quadratic differential on the plane . quadratic differentials are known to play an essential role in the study of conformal and quasi - conformal mappings , univalent functions , etcetera . teichmller @xcite , based on the fundamental work of grtzsch , formulated a principle according to which quadratic differentials and their singularities are associated with the solutions of extremal problems in geometric function theory . although he did not prove any general result supporting his principle , we should give credit to teichmller for putting spotlight on quadratic differentials . schiffer @xcite introduced several variational techniques in the geometric function theory , allowing to find differential equations for the boundaries of the extremal domains , which in turn give a more formal connection with quadratic differentials . see @xcite for further details . as it was mentioned above , the riemann - hilbert asymptotic analysis for @xmath3 matrix - valued functions characterizing the non - hermitian orthogonality provides another natural connection with quadratic differentials : the `` right '' level curves for the @xmath2-functions , that usually have a quite complicated structure , are trajectories of a suitable quadratic differential . thus , the problem of existence of the appropriate curves can be reduced to the question about the global structure of such trajectories . this is not a simplification ( the description of the global structure can be a formidable task ) , but it opens the gate to other techniques from the geometric function theory . these ideas have been successfully applied by bertola @xcite , being closely related ( in fact , in some sense equivalent ) to the max - min approach mentioned before , see also @xcite . in the same spirit and in a much more explicit form , quadratic differentials also appeared in similar asymptotic problems in @xcite . we emphasize that in all these problems , the underlying quadratic differentials are defined on the complex plane . returning to our motivation rooted in the interacting particle systems , recent works have showed that more general models , such as the hermitian matrix model with an external source @xcite , the two - matrix model @xcite , some classes of non - intersecting paths @xcite or the normal matrix model @xcite require considering log gases with more than one group of charges . in this case , standard orthogonal polynomials are not enough , and we must turn to the so - called _ multiple orthogonal polynomials _ and to the associated vector equilibrium problems @xcite . the connection of these two notions was put forward first by gonchar and rakhmanov @xcite , motivated by the analytic theory of hermite pad approximants . the reader interested in further details is advised to look into the monograph by nikishin and sorokin @xcite , which features a nice introduction to vector equilibrium problems from the approximation theory s perspective . although the analytic theory of multiple orthogonal polynomial is still in its infancy , two somewhat extreme cases are fairly well understood ( see e.g. @xcite ) . the first one , known as the angelesco system , corresponds to orthogonality with respect to measures living on disjoint sets , whose asymptotics is described by a vector equilibrium for repelling systems of charges . the other one , called the nikishin system , where on the contrary the orthogonality is defined on the same set for all measures , is governed by a system of mutually attracting charges . in both situations the size of the charged ensembles is fixed . from the recent works of aptekarev @xcite and rakhmanov @xcite it became apparent that the `` intermediate '' cases require more complex log - gases models for their asymptotic descriptions , mixing both attracting and repelling charges , as well as allowing for charges `` flowing '' from one ensemble to another , see sections [ sec : mainresults ] and [ section_general_variational ] below . in the context of the non - hermitian orthogonality , multiple orthogonal polynomials yield naturally the notion of the _ critical vector - valued measures _ , defined again as saddle points ( and thus , solutions of some variational problems ) for the total logarithmic energy . in the same vein as the standard non - hermitian orthogonality can be characterized by a @xmath3 matrix valued riemann - hilbert problem @xcite , the multiple orthogonality can be associated with larger ( @xmath4 , @xmath5 ) matrix valued riemann - hilbert problems @xcite . some heuristics ( that in some situations can be made rigorous using the wkb approximation arguments @xcite ) indicates that the asymptotics of multiple orthogonal polynomials ( and the critical vector - valued measures ) can be described using higher - order algebraic equations . this is indeed the case , as it follows from some previous works and from the results of this paper . some instances of the critical vector - valued measures have appeared in literature , basically in the study of the limit zero distribution of some multiple orthogonal polynomials satisfying non - hermitian orthogonality conditions . the most studied cases are those presenting strong symmetry , so that the support of these measures can be easily derived . other works , such as @xcite , consider non - symmetric situations . their basic approach is to start from a general form expected for a cubic equation that should govern the system , and then make a genus ansatz , hence reducing the free parameters of the equation to a minimum . although a vector equilibrium is present , due to the explicit form of the deduced algebraic equation its detailed study is not needed and usually bypassed . moreover , in such situations there is no external field involved , which is indeed a considerable simplification , even in the scalar case . one of our main motivations is to understand the structure of the critical vector - valued measures with harmonic external fields . we follow the approach initiated in @xcite , and show that the variational method , applied to critical measures , allows to deduce the corresponding algebraic equation ( spectral curve ) and the associated trajectories of a quadratic differential , now on a compact riemann surface instead of the plane , whose analysis will be the central part of this paper . assume we are given a vector of three non - negative measures @xmath6 , compactly supported on the plane . for the interaction matrix @xmath7 and vector of real - valued functions ( `` external fields '' ) @xmath8 @xmath9 where @xmath10 are polynomials are rational , we restrict ourselves here to the given matrix @xmath7 and the polynomial external fields ; these choices avoid some technicalities related to cumbersome notation and the order or coincidence of the poles . ] , and denoting by @xmath11 the logarithmic energy of two compactly supported measures @xmath12 and @xmath13 , we consider the total energy functional of the form @xcite @xmath14 matrix @xmath7 is symmetric , singular and positive - semidefinite . its only non - zero eigenvalue ( of order 2 ) is @xmath15 , and the corresponding eigenspace is given by the vectors @xmath16 ( in what follows , @xmath17 stands for the transpose ) satisfying @xmath18 as it will be seen below , the external fields in must satisfy the compatibility condition of @xmath19 being an eigenvector for the eigenvalue @xmath15 , that is , @xmath20 we complete the description of the electrostatic model by introducing the constraints on vector - valued measures under consideration : given a parameter @xmath21 $ ] , we require that @xmath6 satisfies @xmath22 denotes the total mass ( total variation ) of the measure @xmath12 . it should be pointed out that a particular case of this model ( with all @xmath23 and @xmath24 ) appears in the work of aptekarev @xcite and rakhmanov @xcite in their study of hermite - pad approximants @xcite . notice that @xmath7 in contains submatrices that are the interaction matrices both for the angelesco and for the nikishin cases . let us denote by @xmath25 the plane lebesgue measure on @xmath26 . we are interested in the existence of critical vector - valued measures within a family @xmath27 of measures @xmath6 satisfying plus the following conditions : * each @xmath28 , @xmath29 , is a non - negative borel measure , supported on a compact set in @xmath26 of zero plane lebesgue measure , @xmath30 and such that the energy @xmath31 , defined in , is finite . * the set @xmath32 is finite , @xmath33 the _ vector equilibrium problems _ deal with the minimizers of the energy functional over a family of measures @xmath34 living on prescribed ( and fixed ) subsets of @xmath26 , see e.g. @xcite and the references therein . as it follows from @xcite , the equilibrium measure ( global minimizer of @xmath31 ) , if it exists in the class @xmath27 , is unique . here we consider a natural extension of the notion of vector equilibrium for the conducting plane : the _ critical vector - valued measures _ , defined as follows . for @xmath35 and @xmath36 , denote by @xmath37 the pushforward measure of @xmath12 induced by the variation of the plane @xmath38 , @xmath39 . [ def : criticalmeasures ] we say that for @xmath21 $ ] , @xmath40 is an _ @xmath41-critical measure _ ( or a saddle point of the energy @xmath42 ) if @xmath43 , and @xmath44 for every function @xmath36 . sometimes , when the value of @xmath41 is irrelevant or is clear from the context , we will simplify the terminology speaking simply about _ critical measures_. in order to formulate our first results we introduce some notation . given a ( scalar ) non - negative borel measure @xmath45 , compactly supported on the plane , we denote by @xmath46 its logarithmic potential , which is harmonic in @xmath47 and superharmonic in @xmath26 . additionally , the principal value of the cauchy transform @xmath48 is analytic in @xmath47 , and @xmath49 with @xmath50 the interaction matrix @xmath7 in satisfies the following identities : @xmath51 where @xmath52 is the @xmath53 identity matrix . for a vector of measures @xmath54 , define the vector of functions @xmath55 through the equality @xmath56 where @xmath57 . alternatively , the functions @xmath58 are given explicitly as @xmath59 it was proved in ( * ? ? ? * section 5 ) ( see also @xcite ) that the cauchy transform of a scalar critical measure is a solution of a quadratic equation @xmath25-a.e . on @xmath26 , which is a characterizing property of such measures . our first result is a natural generalization of this property to the critical vector - valued measures : [ thm_spectral_curve ] suppose that for @xmath21 $ ] , @xmath60 is an @xmath41-critical measure in the sense of definition [ def : criticalmeasures ] . then there exist a polynomial @xmath61 and a rational function @xmath62 with poles of order at most @xmath63 such that the functions @xmath58 in satisfy @xmath25-a.e . on @xmath26 the algebraic equation @xmath64 the polynomial @xmath61 is given by @xmath65 moreover , each of the measures @xmath66 is supported on a finite union of analytic arcs , and they are absolutely continuous with respect to the arclength measure of their supports . each pole @xmath67 of @xmath62 , if exists , belongs to the support of at least two of the measures @xmath68 , @xmath69 , @xmath70 , and for each such a measure @xmath71 its density satisfies @xmath72 for some nonzero constant @xmath73 ( which may depend on @xmath67 and @xmath74 ) , where @xmath75 is the order of @xmath67 as a pole of @xmath62 . we also prove a converse to theorem [ thm_spectral_curve ] . [ thm_reciprocal_spectral_curve ] suppose that for @xmath21 $ ] , @xmath60 is such that the measures @xmath66 are supported on a finite union of analytic arcs , and are absolutely continuous with respect to the arclength . if for some polynomials @xmath76 with @xmath77 the functions @xmath78 satisfy an algebraic equation of the form for a polynomial @xmath61 and a rational function @xmath62 , then @xmath79 is a critical measure for the energy functional and the external fields defined by @xmath80 notice that with the definition and the compatibility condition the equalities take the form . few remarks are in order . theorems [ thm_spectral_curve ] and [ thm_reciprocal_spectral_curve ] show that there is a clear connection between critical measures and cubic equations of a specific form . the fact that the equation is cubic has to do with the rank of the interaction matrix @xmath7 in , which is 2 : from the proofs it is natural to expect that critical measures ( with @xmath81 components ) for an energy functional with an interaction matrix of rank @xmath82 should be related to algebraic equations of degree @xmath83 . furthermore , the compatibility condition has to do with the structure of the interaction matrix , and finds its expression also in the absence of the @xmath84 term in the algebraic equation . equation and the structure of should be seen as normalization conditions , ensuring that the underlying energy functional is of the precise form . different choices for these identities would lead to a different interaction matrix in . the notion of the critical vector - valued measures can be extended to accommodate also log - rational external fields and domains with non - trivial boundaries ( `` hard edges '' , in the terminology of random matrix theory ) . the variations of the energy in these situations must allow for fixed points , see @xcite for the scalar case . fixed points and singularities of the external fields will appear among possible points of blow - up of the density of the critical measures , and also as possible poles of the coefficients @xmath61 and @xmath62 in . finally , a reader familiar with the notion of the scalar equilibrium and scalar critical measures might be puzzled by the fact that we allow for a blow - up of the densities of such measures in the case of the polynomial external fields . indeed , in the scalar case all critical measures in such circumstances have uniformly bounded densities on the whole complex plane @xcite . this is no longer the case in the vector case , as the following two examples illustrate : they show that the components of the critical vector - valued measures can create `` artificial hard edges '' , obstructing each other and presenting unbounded densities when it was not expected , i.e. not created by the external field or by the boundaries of the conducting domain . [ example_angelesco ] consider the algebraic equation @xmath85 it has simple branch points at @xmath86 , and a double branch point at @xmath87 , and three solutions @xmath88 specified by their behavior as @xmath89 : @xmath90 with @xmath91 . a direct calculation shows that there are two measures , @xmath68 , living on @xmath92 $ ] , and @xmath93 , such that @xmath94 , and @xmath95 , \\ c^{\mu_2}(z ) & = -1-\xi_3(z ) , \quad z\in { \mathbb{c}}\setminus [ 0 , 3\sqrt{3}/2].\end{aligned}\ ] ] hence theorem [ thm_reciprocal_spectral_curve ] shows that @xmath96 is a @xmath97-critical vector - valued measure , according to definition [ def : criticalmeasures ] , corresponding to the interaction matrix and the polynomial external fields given by @xmath98 notice however that the densities of both measures @xmath28 , @xmath99 , blow up at @xmath87 as @xmath100 . it is worth mentioning that the same pair of measures @xmath101 solves the angelesco - type vector _ equilibrium _ problem of minimizing under the assumptions @xmath102,\quad \operatorname{supp}\mu_2 \subset [ 0,+\infty),\quad |\mu_1|=|\mu_2|=\frac{1}{2 } , \quad \mu_3=0.\ ] ] this equilibrium problem does exhibit a hard edge at the origin , and the proof is based on the same type of energy variation , but leaving @xmath87 as a fixed point . it should be pointed out that a similar problem ( but on finite intervals ) was analyzed first by kalyagin in @xcite . [ example_bertola ] let us consider now the following cubic equation , which ( up to a certain rescaling ) have appeared already in @xcite : @xmath103 as in the example [ example_angelesco ] , it has simple branch points at @xmath86 , and a double branch point at @xmath87 . let @xmath104 denote the branch of the square root in @xmath105 $ ] with positive boundary values on @xmath106 from the upper half plane , and let @xmath107 also have positive boundary values on the same interval from the upper half plane . then @xmath108 is holomorphic in @xmath105 $ ] , and @xmath109 is holomorphic in @xmath110 $ ] . moreover , cardano s formula shows that @xmath111 is a solution of ; the other two solutions are given by @xmath112 for the selected branch of @xmath108 , the @xmath113 boundary values of @xmath111 on @xmath114 from the upper and lower half plane , respectively , satisfy @xmath115 thus , @xmath116 is a positive unit borel measure on @xmath117 $ ] , and its cauchy transform is @xmath118.\ ] ] analogously , @xmath119 is a positive unit borel measure on @xmath120 $ ] , and @xmath121.\ ] ] theorem [ thm_reciprocal_spectral_curve ] shows that @xmath122 is a @xmath97-critical vector - valued measure , according to definition [ def : criticalmeasures ] , corresponding to the interaction matrix and the polynomial external fields given by @xmath123 notice that now the densities of both measures @xmath28 , @xmath124 , blow up at @xmath87 as @xmath125 . the next example illustrates that in theorem [ thm_reciprocal_spectral_curve ] we can not discard the degenerate cases when the coefficient @xmath62 in is identically zero , or other situations when becomes reducible over the field of rational functions : [ example_scalar_critical_measure ] if @xmath12 is a scalar critical measure for the external field @xmath126 , where @xmath127 is a polynomial , then there exists a polynomial @xmath128 for which @xcite @xmath129 if we set @xmath130 then @xmath131 which shows that the vector - valued measure @xmath132 is @xmath41-critical for @xmath133 . the function @xmath134 in becomes zero , whereas @xmath111 , @xmath135 are analytic continuations of each other across @xmath136 . from the proof of theorem [ thm_spectral_curve ] in section [ section_general_variational ] we conclude that the corresponding algebraic equation is then reducible and has the form @xmath137 where @xmath128 is the polynomial in . reciprocally , if the cauchy transform of a probability measure @xmath12 satisfies an algebraic equation of the form for some polynomials @xmath127 and @xmath128 , then the construction just carried out combined with theorem [ thm_reciprocal_spectral_curve ] gives us that @xmath12 is a scalar critical measure for the external field @xmath126 . in very much the same spirit , if we now set @xmath138 then the energy of @xmath139 is also given by , showing again that @xmath139 is @xmath41-critical , now for @xmath140 . the respective functions @xmath141 are analytic continuation of each other across @xmath136 , whereas @xmath142 on @xmath26 , and the corresponding algebraic equation is reducible to the form . the critical measure in violates the assumption , but the conclusions of theorem [ thm_spectral_curve ] still hold . however , condition can not be simply dropped , as the following example shows : [ example_arno ] let @xmath143 , @xmath144 be two arbitrary polynomials . for @xmath24 and the polynomial vector external field @xmath145 , @xmath146 , satisfying , consider the vector - valued measure @xmath147 , with @xmath148 the total energy of @xmath79 is @xmath149 thus , if @xmath12 is a _ scalar _ probability critical measure in the external field @xmath150 then for @xmath34 takes place . in other words , @xmath79 is @xmath97-critical in the external field @xmath151 . however , the statement of theorem [ thm_spectral_curve ] does not hold : each of the corresponding functions @xmath58 in satisfies an algebraic equation of degree @xmath63 , but if @xmath152 , these equations can not be combined into a single algebraic equation of degree @xmath153 . to be more precise , calculations in the spirit of the proof of theorem [ thm_spectral_curve ] in section [ section_general_variational ] below show that if @xmath128 is the polynomial in the right hand side of the equation for @xmath12 ( with @xmath154 ) , then @xmath155 clearly , the only assumption not satisfied by the measure @xmath79 in this example is . a consequence of theorem [ thm_spectral_curve ] is that the set @xmath156 is a finite union of disjoint analytic arcs , each of them contained in exactly one of the supports @xmath157 . any orientation of an arc @xmath158 defines its left and right sides , as well as the left ( or @xmath159 ) and right ( or @xmath160 ) continuous boundary values of each @xmath88 on @xmath161 , that we denote by @xmath162 . in what follows , we use extensively ( and without further warning ) the notation mod @xmath153 , so that @xmath163 , @xmath164 and so forth . since @xmath88 s are the three branches of the cubic equation , assumption implies that for any curve @xmath165 there exists an index @xmath166 such that @xmath167 critical measures are intimately connected with vector equilibrium problems and the vector symmetry ( @xmath1-property ) , as it is evidenced by the next theorem . [ thm_s_property ] given @xmath166 , let @xmath161 be an open analytic arc in @xmath168 , not containing any branch point of . there exists a constant @xmath169 for which both the euler - lagrange variational equation ( _ equilibrium condition _ ) @xmath170 and the @xmath1-property @xmath171 hold true for @xmath172 , where @xmath173 are the unit normal vectors to @xmath161 , pointing in the opposite directions . if , for @xmath29 , the constants @xmath174 above are independent of the connected component @xmath161 of @xmath175 , and additionally satisfy @xmath176 , then the critical vector - valued measure is the equilibrium measure for the vector of contours @xmath177 , see ( * ? ? ? * theorem 1.8 ) . examples of critical but non - equilibrium measures in the scalar case are well - known ( see e.g. @xcite ) . using the construction of example [ example_scalar_critical_measure ] , in particular , we can easily build vector critical non - equilibrium measures . the @xmath1-property is the natural generalization of the scalar @xmath1-property , taking into account that in those arcs the potentials of the measures @xmath178 and @xmath179 are harmonic . critical vector - valued measures @xmath79 are also closely connected with trajectories of a quadratic differential on the riemann surface @xmath180 of the algebraic equation , with @xmath181 the sheets are connected across arcs in @xmath182 according to the following rule : if for @xmath165 the condition holds , then we connect the sheets @xmath183 and @xmath184 through @xmath161 crosswise , identifying the @xmath185-side of @xmath161 on @xmath183 with its @xmath186-side on @xmath187 . as usual , we regard the solutions @xmath58 in as branches of the same meromorphic function @xmath188 , defined by , so that function @xmath88 is the restriction of @xmath189 to the sheet @xmath190 of the riemann surface @xmath191 . [ thm_quadratic_differential ] let @xmath192 then @xmath193 extends to a meromorphic function on @xmath191 . moreover , @xmath194 is a meromorphic quadratic differential on @xmath191 with possible poles only at the points at @xmath195 . finally , for @xmath196 , each arc of @xmath175 is an arc of trajectory of @xmath197 . as it was mentioned in section [ sec : historical ] , the connection between quadratic differentials and critical ( or equilibrium ) measures is not new . for scalar critical measures , the quadratic differential can be globally projected on the complex plane , so it is not necessary to consider it on a non - trivial riemann surface . even for vector - valued measures , this connection has been exploited before , see for instance @xcite , but only locally on the plane . to our knowledge , theorem [ thm_quadratic_differential ] is the first time this connection is stated on the whole surface @xmath191 , which provides a powerful tool for construction of critical measures . [ remark : angelesco - nikishin ] assume that at @xmath198 we have with @xmath199 ( see theorem [ thm_spectral_curve ] ) . then @xmath67 is a triple branch point of @xmath191 , so that the local coordinate for @xmath191 at @xmath198 is @xmath200 . theorem [ thm_quadratic_differential ] asserts that @xmath175 lives on trajectories of the quadratic differential @xmath197 defined in , which in this local coordinate takes the form @xmath201 , @xmath202 . if @xmath203 ( or equivalently if the polynomial @xmath62 in has a simple pole at @xmath67 ) , then by the local structure of the trajectories , their canonical projection from @xmath191 onto @xmath26 consists of two analytic arcs intersecting at @xmath67 perpendicularly ( a `` cross '' ) . as example [ example_angelesco ] shows , this configuration can correspond to the interaction of two repulsive measures , and @xmath67 can potentially belong to the intersection of the three components @xmath28 . however , for @xmath204 ( which means that @xmath62 has a double pole at @xmath67 ) the canonical projection of the trajectories from @xmath191 onto @xmath26 at @xmath67 consists of a single analytic arc through this point . it implies , due to , that in this case @xmath67 belongs to the intersection of at most two ( and then , exactly two ) components of @xmath79 ; moreover , it will be the endpoint of an arc in each of the supports . a quick analysis of the cubic branching shows that these two positive measures can not interact repulsively ( `` angelesco '' interaction ) , and hence , must attract each other ( `` nikishin '' interaction ) . thus , example [ example_bertola ] represents ( at least , locally ) the most generic case of the @xmath205-blowup of the density of a critical vector - valued measure . we should point out that plays a substantial role for theorem [ thm_spectral_curve ] , but the conclusion of theorem [ thm_reciprocal_spectral_curve ] still holds true even if we drop completely . in this situation , if @xmath161 is an analytic arc contained in the support of at least two of the measures @xmath66 , and @xmath206 on @xmath161 , then we can choose an orientation on @xmath161 for which @xmath207 the euler - lagrange equation holds true for the three measures @xmath66 ( and possibly different constants @xmath208 ) , and with respect to the orientation the @xmath1-property now becomes @xmath209 the conclusion of theorem [ thm_quadratic_differential ] is also valid in this situation ( with appropriate gluing of the sheets of @xmath191 across the overlaps of the supports ) . however , we do not know whether there are positive measures with non - trivial overlapping supports for which the functions are the three solutions to the same cubic equation as in theorem [ thm_reciprocal_spectral_curve ] . in order to illustrate the results stated above we analyze in depth the interesting and highly non - trivial cubic case , corresponding to the energy functional , with @xmath210 so that the external fields are @xmath211 in what follows , we consider only the values of the parameter @xmath212 ; see the discussion in the remark [ restrictiononalpha ] and also in the introduction to section [ section_cubic_main ] . we build a continuous one - parameter family of critical vector - valued measures @xmath79 by choosing in the coefficients @xmath213 where @xmath214 is the real parameter given by @xmath215 [ thm_genus_zero ] for @xmath212 , there exists a one - parameter family @xmath216 of critical measures for the potentials for which the corresponding algebraic equation has coefficients . moreover , for any such a critical measure , if the associated algebraic equation defines a riemann surface of genus @xmath217 , then its coefficients are given by for some choice of the cubic root in . [ remarkaboutthegenus ] as it follows from the proof of this theorem in section [ section_cubic_spectral_curve ] ( see also remark [ rem : qdfordifferentc ] ) , there are other choices for the coefficient @xmath73 that yield critical vector - valued measures , but for which the associated riemann surface is of genus 1 . we do not consider this case here . theorem [ thm_equilibrium_conditions_cubic ] below ( see also remark [ rem_equilibrium_conditions_cubic ] ) shows that the measures @xmath218 from theorem [ thm_genus_zero ] are in fact equilibrium measures on an appropriate family of contours in @xmath219 . for the critical measure @xmath220 given by theorem [ thm_genus_zero ] , the algebraic function @xmath189 defined by has two real branch points @xmath221 and two nonreal branch points @xmath222 , @xmath223 ( @xmath224 ) . the support of the components @xmath28 of the critical measure @xmath225 can be easily described ; we show that it exhibits a phase transition for a certain value of @xmath41 : [ thm_existence_critical_measures_cubic ] there exists a critical value @xmath226 , determined by @xmath227 where @xmath228 are the functions in , such that * if @xmath229 then @xmath230 , @xmath231 $ ] , and @xmath232 is an analytic arc , disjoint from @xmath233 and connecting the branch points @xmath234 . * if @xmath235 then none of the measures is zero , and there exists a value @xmath236 , determined by the condition @xmath237 for which @xmath238 $ ] , @xmath239 $ ] and @xmath240 , where @xmath241 is an analytic arc on the upper half plane connecting @xmath222 to @xmath242 , and @xmath243 is its complex conjugate arc . .5 figure_01a.pdf .5 figure_01b.pdf we refer to figure [ figure_supports ] for an actual numerical evaluation of the supports of the measures @xmath66 in theorem [ thm_existence_critical_measures_cubic ] . [ restrictiononalpha ] the restriction @xmath244 arises somewhat naturally in our analysis . for @xmath24 , the algebraic equation with coefficients still defines a vector - valued measure @xmath245 in the sense of theorem [ thm_reciprocal_spectral_curve ] , but the support of its third component is unbounded ; hence , strictly speaking the measure @xmath245 does not belong to @xmath246 . in rough terms , theorems [ thm_spectral_curve ] and [ thm_reciprocal_spectral_curve ] induce a map @xmath247 and theorems [ thm_genus_zero ] and [ thm_existence_critical_measures_cubic ] characterize this map completely for a subclass of algebraic equations and the cubic potential . the existence of the critical measure @xmath79 assured by theorem [ thm_genus_zero ] and the topological description of its support given by theorem [ thm_existence_critical_measures_cubic ] follow after a careful analysis of the associated quadratic differential @xmath197 in . we describe the critical graph of @xmath197 for @xmath133 and indicate its subsets corresponding to the supports @xmath248 . in other words , we lift the supports to the associated riemann surface , embedding them into the critical graph of @xmath197 . we then deform the parameter @xmath41 in the interval @xmath249 , observing the dynamics of the critical graph and keeping track of the supports of the measures . during this deformation procedure , the critical graph of @xmath197 displays several transitions , described in sections [ section_degenerate][section_trajectories_tau2_1 - 4 ] , but only one of such transitions , governed by equation , has direct impact on the topology of @xmath157 . it should be stressed that there are not many tools for such an analysis ( we have summarized the basic facts about quadratic differentials in the appendix [ appendix_quadratic_differentials ] ) , and that it can be extremely complicated , even on the riemann sphere . the situation becomes even more involved when we consider trajectories on a more general compact riemann surface . we believe that the methodology we have developed is of independent interest , and can be applied in other situations as well . the critical measure given by theorem [ thm_genus_zero ] is crucial in the study of multiple orthogonal polynomial @xmath250 defined through @xmath251 where @xmath252 and @xmath253 are contours extending to @xmath195 with angles @xmath254 , @xmath217 and @xmath255 , respectively . it turns out that the asymptotic behavior of @xmath256 as @xmath257 in such a way that @xmath258 , is governed by this critical vector - valued measures @xmath259 : under this regime , the sequence of zero counting measures associated with @xmath260 converges to the sum of the first two components of @xmath79 . the two extremal cases , @xmath133 and @xmath24 , have been proved in @xcite and @xcite , respectively , and the general case @xmath261 will be addressed in a follow - up publication @xcite . as we already mentioned , zeros of orthogonal polynomials on the real line are characterized as solutions to logarithmic equilibrium problems . the measure @xmath34 given by theorem [ thm_genus_zero ] , and hence the zeros of the multiple orthogonal polynomials , also admits a vector equilibrium problem characterization , as explained next . let @xmath262 be the class of contours @xmath161 extending to @xmath195 with angles @xmath255 and intersecting the real axis exactly once , say at @xmath263 . denote by @xmath264 the subset of measures @xmath265 that further satisfy @xmath266.\ ] ] the @xmath41-_equilibrium measure _ @xmath267 of @xmath268 ( for the energy functional @xmath42 given in with ) is the unique measure @xmath269 for which @xmath270 [ thm_equilibrium_measure_cubic ] for @xmath261 , there exists a contour @xmath271 for which its @xmath41-equilibrium measure is the @xmath41-critical measure @xmath79 given by theorem [ thm_genus_zero ] . we conjecture that the contour @xmath272 is characterized by the max - min property @xmath273 this characterization would be analogous to the max - min property for non - hermitian orthogonal polynomials @xcite . furthermore , an adaptation of the methods in @xcite shows that the @xmath41-equilibrium measure of any contour solving this max - min problem is in fact an @xmath41-critical measure . theorems [ thm_spectral_curve ] , [ thm_s_property ] , [ thm_quadratic_differential ] , and a simplified version of theorem [ thm_reciprocal_spectral_curve ] are proven in section [ section_general_variational ] ( the complete proof of theorem [ thm_reciprocal_spectral_curve ] is rather technical and thus deferred to appendix [ appendix1 ] ) . in section [ section_cubic_spectral_curve ] we derive the coefficients and prove the second part of theorem [ thm_genus_zero ] . assuming the existence of certain short trajectories ( fact proved later , in section [ section : dynamics ] ) , we derive the first part of theorem [ thm_genus_zero ] and theorem [ thm_equilibrium_conditions_cubic ] in section [ section_spectral_curve_to_variational_equations ] , which yields theorem [ thm_equilibrium_measure_cubic ] . section [ section : dynamics ] is devoted to the analysis of the global structure of the quadratic differential for the cubic potentials , which also provides a proof of theorem [ thm_existence_critical_measures_cubic ] ( or equivalently , of theorem [ thm : criticaltraj ] , where the structure of the support of the critical vector - valued measure is rephrased in the terminology of quadratic differentials ) . finally , two more appendices contain the minimal background on quadratic differentials ( appendix [ appendix_quadratic_differentials ] ) and the description of the numerical experiments and procedures used in this paper ( appendix [ appendix_numerics ] ) . critical measures were defined in the previous section in terms of the vanishing of the total energy . here we use an alternative characterization , more convenient for calculations . when @xmath274 is a scalar measure , the following proposition [ proposition_local_variation_energy ] coincides with ( * ? ? ? * lemma 3.1 ) . the proof extends trivially to vectors of measures @xmath34 and polynomial external fields as considered here . we skip the details . [ proposition_local_variation_energy ] for any vector of measures @xmath275 , it is valid @xmath276 where @xmath277 although the definition of critical measures only requires to evaluate @xmath278 for test functions @xmath36 , the quantity @xmath278 as defined above will be used for any function defined on @xmath279 , as long as the integrals on the right - hand side of exist . in particular , considering @xmath280 and @xmath281 , we get from proposition [ proposition_local_variation_energy ] [ corollary_critical_measure ] a measure @xmath275 is critical if , and only if , @xmath282 for every function @xmath36 . the following lemma is inspired by @xcite , where a similar situation ( but involving only one measure ) was analyzed , and borrowed in the following form from ( * ? ? ? * lemma 3.5 ) , where a simplified proof is given . the proof from @xcite is easily extended to our situation by simply choosing @xmath283 therein and mimicking the arguments . [ lemma_extension_test_functions ] suppose @xmath34 is a critical vector - valued measure . if @xmath284 satisfies @xmath285 then @xmath286 for the meromorphic function @xmath287 the next result is straightforward , and we skip its proof : [ lemma_integrability_cauchy_transform ] let @xmath288 be holomorphic in a punctured neighborhood of @xmath289 . if @xmath290 is @xmath25-locally integrable at @xmath67 for some @xmath291 , then @xmath67 is either a removable singularity or a pole of @xmath288 of order @xmath292 . for any finite borel measure @xmath12 , it follows from tonelli s theorem that the function @xmath293 is locally @xmath25-integrable and in particular finite @xmath25-a.e . ; that is , is satisfied for @xmath25-a.e . hence the cauchy transform @xmath295 of the measure @xmath12 is finite @xmath25-a.e . in particular , the functions @xmath58 in are finite @xmath25-a.e . and locally integrable with respect to @xmath25 , so that @xmath296 is well - defined @xmath25-a.e . and is analytic on open subsets of @xmath297 . recall the quantities @xmath61 , @xmath278 and @xmath298 defined in , and , respectively . the next lemma is crucial for what comes later : [ lemma_polynomial_coefficient ] if @xmath43 , then the functions @xmath88 defined in satisfy the identity @xmath299 moreover , the statements 1 . @xmath300 is a polynomial , 2 . @xmath301 @xmath25-a.e . 3 . @xmath302 for every @xmath303 satisfying , are equivalent . for @xmath304 , @xmath305 and @xmath306 where @xmath307 notice that the integrand in the right - hand side of is a polynomial both in @xmath308 and in @xmath303 , and thus ( since @xmath28 is finite and compactly supported ) it is also @xmath309-integrable for all @xmath303 . hence , @xmath310 is a bona fide polynomial . additionally , and also show that @xmath311 is finite whenever holds true . using and in , we get that @xmath312 or equivalently , @xmath313 with the previously used notation @xmath57 and @xmath19 . on the other hand , by ( and taking also into account both identities from ) we get @xmath314 notice that the compatibility condition means precisely that @xmath315 , so that @xmath316 and using we can simplify the expression between brackets above to conclude that @xmath317 where @xmath61 was defined in . this identity is valid for values of @xmath303 satisfying , which proves , as well as the equivalence of _ ( ii ) _ and _ ( iii)_. clearly , _ ( ii ) _ implies _ ( i)_. on the other hand , by , @xmath318 and since function @xmath319 converges uniformly to @xmath217 as @xmath89 , by the dominated convergence theorem we conclude that @xmath320 thus , @xmath321 measures @xmath322 and @xmath70 are compactly supported , so that holds for all @xmath303 sufficiently large , and with , @xmath323 this establishes that _ ( i ) _ implies _ ( ii)_. a combination of corollary [ corollary_critical_measure ] and lemma [ lemma_polynomial_coefficient ] shows that if @xmath34 is critical , then the polynomial @xmath61 in is alternatively expressed as @xmath324 from the expressions it follows that @xmath325 and as a consequence @xmath326 multiplying the identities in by appropriate factors @xmath327 , it follows that @xmath328 define @xmath329 due to , @xmath62 does not depend on the choice of @xmath330 . when we choose @xmath331 , we see that @xmath62 is analytic on @xmath332 . similarly , when we choose @xmath333 , we see that @xmath62 should be analytic on @xmath334 and @xmath335 , respectively . consequently , @xmath62 can only have singularities at @xmath336 , defined in , so from these singularities are all isolated and in a finite number . moreover , @xmath337 where for the last inequality we used @xmath338 , which is valid for any non negative numbers @xmath339 . the function @xmath88 is locally @xmath25-integrable ( see the comments after lemma [ lemma_integrability_cauchy_transform ] ) . hence the function @xmath62 satisfies the conditions of lemma [ lemma_integrability_cauchy_transform ] for @xmath340 and any choice of @xmath341 , so the points in @xmath336 are not essential singularities of @xmath62 . moreover , from the behavior of the @xmath88 s and @xmath61 when @xmath342 , it follows that @xmath62 has polynomial growth at @xmath195 . we conclude that @xmath62 is rational ( although it could be identically zero ) . in summary , we have shown that under the assumptions of theorem [ thm_spectral_curve ] , there exist a polynomial @xmath61 , defined in , and a rational function @xmath62 with possible poles in @xmath336 , such that the functions @xmath111 , @xmath134 , @xmath135 satisfy @xmath343 the fact that all the components @xmath28 are supported on a finite union of analytic arcs , and that they are absolutely continuous with respect to the arclength measure of their supports is then a direct consequence of ( * ? ? ? * theorem 2 ) . let @xmath67 be a pole of @xmath62 . the functions @xmath58 satisfy the cubic equation , so their local behavior near @xmath67 is of the form @xmath344 where @xmath345 and @xmath346 are nonzero constants . since @xmath67 is a pole of @xmath62 and @xmath61 is a polynomial , from we learn the @xmath347 s are all equal , say to @xmath13 , and @xmath75 should be equal to the order of @xmath67 as a pole of @xmath62 . moreover , we further get that none of the functions @xmath141 and @xmath135 is analytic near @xmath67 , so @xmath67 has to belong to the support of at least two of the measures @xmath322 and @xmath70 . on the other hand , since @xmath88 is a linear combination of polynomials and cauchy transforms of finite measures , we must also have @xmath348 , so we conclude @xmath349 the behavior then follows from plemelj s formula and , concluding the proof . the fact that ( scalar ) finite measures , whose cauchy transform satisfies a quadratic equation @xmath25-q.e . , live on a finite set of analytic curves was established in @xcite without any additional constraint on the measure ( the proof was inspired by @xcite ) . this was extended to an arbitrary algebraic equation in @xcite , but with a crucial assumption on the measure that its support has a zero plane lebesgue measure ( this assumption is embedded in the definition of the class @xmath27 in section [ sec : mainresults ] ) . nevertheless , we believe that the assertion about the support is still true even if we drop this a priori restriction on @xmath79 . our next goal is to prove theorem [ thm_reciprocal_spectral_curve ] . in other words , for a vector of measures @xmath350 we assume that the components of @xmath34 are supported on a finite union of analytic arcs , and the associated functions @xmath88 in satisfy an algebraic equation of the form for some polynomial @xmath61 and some rational function @xmath62 . as we already pointed out after the statement of theorem [ thm_reciprocal_spectral_curve ] , these assumptions allow us to write @xmath351 as in for the vector of external fields @xmath352 given by . in particular , it follows that @xmath88 s satisfy and consequently @xmath353 from lemma [ lemma_polynomial_coefficient ] we get immediately the following result : [ corollary_converse_critical_measure ] under the assumptions of theorem [ thm_reciprocal_spectral_curve ] , the vector of measures @xmath79 satisfies @xmath354 for @xmath355 , where @xmath298 is as in . hence , the proof of theorem [ thm_reciprocal_spectral_curve ] is reduced basically to extending the conclusion of corollary [ corollary_converse_critical_measure ] to the whole class of functions @xmath36 . although this is relatively straightforward for @xmath280 analytic in a neighborhood of the union of @xmath175 , it takes more effort beyond the analyticity due to the integrand @xmath356 in . in this case we need to appeal to a `` refined '' version of the celebrated mergelyan s theorem that would allow for an approximation of a given sufficiently smooth function by a sequence of analytic ones , and in such a way that the sequence of derivatives is uniformly bounded . the complete proof we were able to find is rather technical , so for the sake of readability we postpone it to appendix [ appendix1 ] , and present here the arguments valid for the case when @xmath280 vanishes in a neighborhood of the set of double poles of @xmath62 ( or when this set is empty ) . we formulate it as an independent proposition : [ lemma_variations_without_double_poles ] let @xmath275 be a vector of measures satisfying the conditions of theorem [ thm_reciprocal_spectral_curve ] . suppose that @xmath36 satisfies @xmath357 where @xmath358 is the set of double poles of @xmath62 . then @xmath359 . recall that the union of the support of the components of @xmath34 is a finite union of analytic arcs , whose points of intersection are denoted by @xmath336 ( see ) , and the poles of the coefficient @xmath62 in belong to @xmath336 , as it follows from the arguments in . furthermore , if @xmath360 , then @xmath361 for some @xmath362 ( possibly @xmath363 ) . given @xmath280 as above , let us define @xmath364 with @xmath365 where as usual we understand @xmath366 in terms of its principal value ( as in ) , for @xmath367 . with this convention and recalling , on any open analytic arc @xmath161 from @xmath182 , not containing any branch point of , by the sokhotsky plemelj s formula we have @xmath368 where @xmath369 is the radon - nikodym derivative of @xmath28 with respect to the line element on @xmath161 , so that if @xmath370 , we have @xmath371 . let @xmath161 be an open analytic arc from @xmath372 , not containing any branch point of . observe that the matrix @xmath373 in satisfies the identity @xmath374 , where @xmath375 since @xmath376 is continuous across @xmath161 , by , @xmath377 furthermore , the identity @xmath378 holds for all @xmath379 , and we obtain that @xmath380 recall that equation allows us to rewrite as with the external fields given in . from , @xmath381 so that @xmath382 because the functions @xmath88 s satisfy a cubic equation , the boundary conditions are valid and imply the equality @xmath383 where @xmath384 and @xmath385 is the characteristic function of @xmath175 , @xmath196 . the matrix @xmath386 is piecewise constant ; for ease of notation we suppress its @xmath303-dependence in the following computations . since @xmath387 is an eigenvector of @xmath7 corresponding to the eigenvalue @xmath15 ( see section [ sec : mainresults ] ) , we learn from and @xmath388 an immediate consequence of this identity , combined with sokhotsky plemelj s formula @xmath389 , is @xmath390 where as usual , @xmath391 , etcetera . multiplying by @xmath386 and using , we conclude that @xmath392 since @xmath393 we can write it equivalently as @xmath394 recall that @xmath165 was arbitrary , so we can integrate this formula along @xmath372 . by , for @xmath395 we get @xmath396 where we recall that if @xmath397 is discontinuous across @xmath398 , we understand the second integral in the right hand side above in terms of its principal value . by assumption , @xmath399 does not contain double poles of the coefficient @xmath62 , and we use the condition to get the behavior @xmath400 for some @xmath401 and any endpoint @xmath67 of the support of @xmath71 . in particular , this implies that @xmath402 and @xmath397 are @xmath71-integrable , so the integrals in the right - hand side of are convergent . moreover , the behavior allows us to interchange the order of integration for the second integral in the right - hand side of ( see ( * ? ? ? * equation ( 20 ) , page 25 ) ) in order to get @xmath403 again by sokhotsky plemelj s formula , @xmath404 and using it in , we finally conclude that @xmath405 a direct consequence of this formula is that for any @xmath53 constant matrix @xmath406 , @xmath407 in particular , we have @xmath408 where we have used the trivial identity @xmath409 for the last two equalities , and also for the last equality . thus , integrating with respect to @xmath410 , observing that @xmath411 and applying this last identity , we arrive at @xmath412 which is a compact form of writing the condition @xmath413 . for a vector - valued function @xmath414 we understand by @xmath415 the term by term integration , and we denote by @xmath416 the vector whose components are the densities of @xmath66 ( with respect to the complex line element ) along the arcs of @xmath182 . because the supports of the components of @xmath79 are made of analytic arcs , and @xmath417 has analytic components , we conclude that @xmath418 is continuous across the arcs of @xmath182 . integrating and using we get @xmath419 where @xmath420 is a real constant vector which only depends on the connected component of @xmath421 . let @xmath161 be an open analytic arc from @xmath182 , not containing any branch point of . reasoning as for , we have @xmath422 thus , for @xmath172 and @xmath423 the vector of constants for the component on the @xmath185-side of @xmath161 , @xmath424 recalling that @xmath425 this last equation implies @xmath426 if @xmath427 , then @xmath88 continuous across @xmath161 , and tells us that the @xmath428-th entry of @xmath429 vanishes , which in turn yields ( with @xmath430 replaced by @xmath431 ) . note that due to the @xmath1-property on @xmath432 is equivalent to @xmath433_+ \\ = -\left[\frac{\partial}{\partial z}\left(\sum_{k=1}^3a_{4-j , k}u^{\mu_k}+\frac{\phi_{4-j}}{2}\right)\right]_-,\ ] ] equation means that for @xmath434 , @xmath435 where we also used the identity involving @xmath7 and @xmath373 in and @xmath425 . as before , the boundary conditions imply that the entry @xmath428 of @xmath436 vanishes , and the equation above then implies . we denote the restriction of @xmath128 to the sheet @xmath190 by @xmath310 . in cyclic notation mod @xmath153 , @xmath437 can be expressed as @xmath438 clearly @xmath437 is meromorphic in @xmath439 . we first prove that each @xmath437 is meromorphic on the sheet @xmath190 . if @xmath440 , then due to the function @xmath111 is analytic across @xmath272 , hence @xmath441 implying that @xmath442 so @xmath443 is analytic across @xmath272 and , as a consequence , it follows that @xmath443 is meromorphic on the whole sheet @xmath444 . similarly we prove @xmath437 is meromorphic on @xmath190 , @xmath333 . we now show that @xmath193 is globally defined , that is , the function @xmath445 is the analytic continuation of @xmath437 from @xmath190 to @xmath183 , @xmath196 . consider an arc @xmath446 . for the construction of @xmath191 we know that @xmath272 connects exactly two sheets , which we assume to be @xmath444 and @xmath447 , the remaining cases are analogous . then @xmath448 , so the function @xmath135 is analytic across @xmath272 , hence @xmath449 on @xmath272 and @xmath450 so @xmath451 is the analytic continuation of @xmath443 to @xmath447 across @xmath272 . thus , @xmath193 is meromorphic along any arc connecting the sheets . it is clear that the functions @xmath58 , and hence @xmath193 , can only be unbounded at the points at @xmath195 and also at the poles of the coefficient @xmath62 in . if @xmath67 is such a pole , then the three functions @xmath58 are branched at @xmath67 , and the local coordinate of @xmath191 at @xmath198 is of the form @xmath452 , @xmath453 , and hence @xmath454 since @xmath67 is at most a double pole of @xmath62 , it follows from the identities @xmath455 that the functions @xmath58 all blow up with the same order @xmath456 , @xmath457 , that is @xmath458 for some nonzero constants @xmath346 , so @xmath459 for some constant @xmath73 . combining with , we get @xmath460 for some constant @xmath461 . since @xmath462 , we get that @xmath197 has to remain bounded near @xmath67 , and hence @xmath197 can only have poles at the points at @xmath195 . let @xmath463 be an open arc . due to assumption , function @xmath135 is analytic across @xmath161 . now the definition of function @xmath111 in , the sokhotsky - plemelj s formula and yield that for @xmath464 , @xmath465 analogously , if @xmath466 , then @xmath134 is analytic across @xmath161 , and for @xmath464 , @xmath467 finally , if @xmath468 , then @xmath111 is analytic across @xmath161 , and using again the definition of @xmath135 in and the sokhotsky - plemelj s formula , we get that for @xmath464 , @xmath469 this shows that the measures @xmath28 must be supported on arcs of trajectories of @xmath197 . in the following two sections we deal with the cubic case , and describe a one - parameter family of critical vector - valued measures for the energy functional and for the choice , so that the external fields are given by . although the @xmath41-critical measures were defined for @xmath21 $ ] , here we restrict our attention to @xmath470 $ ] . as it will follow from our analysis below , as @xmath471 , the support of the component @xmath70 of the @xmath41-critical measure becomes unbounded . furthermore , our original motivation was the asymptotic analysis of the multiple orthogonal polynomials , for which the case of @xmath472 $ ] can be easily reduced to @xmath473 $ ] by an appropriate rotation of the plane . thus , the selection of this interval for @xmath41 is natural in the present situation , although our method carries over without any special difficulty to the whole range of @xmath41 . recall that by theorem [ thm_spectral_curve ] the shifted resolvents , defined in , of any critical vector - valued measure @xmath40 satisfy the algebraic equation ( `` spectral curve '' ) . as a first step , we deduce the expressions for its coefficients . for the potentials as in , the coefficient @xmath61 in reduces to @xmath474 where at this moment the constant @xmath73 is given in the form @xmath475 since @xmath476 , comparing the expansions of both expressions at @xmath195 and using , we further get that @xmath477 and @xmath478 observe that @xmath479 is an equivalent parametrization that gives a bijection between the interval @xmath480 $ ] and @xmath481 $ ] . as it was mentioned in section [ sec : max_min ] , the extremal cases , @xmath482 and @xmath483 , were studied in @xcite and @xcite , respectively , in their connection to the multiple orthogonal polynomials , for the choices @xmath484 and @xmath485 , respectively , and the family of critical measures depending on @xmath261 are also relevant to the asymptotic analysis of these polynomials for general @xmath486 . from a different perspective , we are studying a continuous deformation of the critical measures , interpolating the extremal cases of @xmath482 and @xmath483 . the discriminant of with respect to the variable @xmath189 is @xmath487 ( 81 - 324\tau)z^6 + 54c z^5 + 9c^2 z^4 + 54(9\tau-2)z^3 \\ + \ , 54c(3\tau-2)z^2 - 36c^2z-4c^3 - 243\tau^2 . \end{aligned}\end{aligned}\ ] ] since @xmath488 is a polynomial in @xmath303 of degree @xmath489 , if the riemann surface of has genus @xmath217 then , by the riemann - hurwitz theorem , @xmath488 must have a multiple root . in particular , the discriminant @xmath490 of @xmath488 must vanish . a cumbersome but straightforward calculation ( that can be carried out with the aid of a symbolic algebra software such as mathematica ) shows that @xmath491 for a nonzero real constant @xmath492 and @xmath493 so we expect @xmath73 to be a root of either @xmath494 or @xmath495 . for the case @xmath496 studied in @xcite , the algebraic equation reduces to @xmath497 showing that @xmath498 , which is a root of @xmath494 . by continuity , we expect @xmath73 to be a root of @xmath494 for every choice of @xmath499 , concluding that @xmath500 or @xmath501 which is the same as . obviously , @xmath73 defined by can take three possible values ; for the rest of the paper we choose @xmath73 to be real ( and thus , negative ) , so that the algebraic equation is also real . it should be pointed out that a different choice of @xmath73 would lead to an algebraic equation corresponding to another triplet of critical measures @xmath79 , that can be obtained from the original one by rotation by @xmath502 . for the choice of @xmath73 in , we can rewrite @xmath488 as @xmath503 where @xmath504 are given by @xmath505 for @xmath506 the discriminant of @xmath507 is @xmath508 which never vanishes , and we conclude that @xmath507 has always four distinct roots . for the choice @xmath509 , @xmath507 has two complex conjugate roots and two real roots , so this also holds for any @xmath510 . the resultant of @xmath511 and @xmath512 is @xmath513 so that in the interval @xmath514 , the polynomials @xmath507 , @xmath512 share a root only when @xmath515 . it then follows that for @xmath516 the roots of @xmath507 are branch points of multiplicity @xmath63 of . if the double zero @xmath517 of @xmath518 ( that is , the zero of @xmath512 ) is a branch point of , then its multiplicity ( as a branch point ) has to be three . this means that the three solutions to should coincide for @xmath519 , so has to share a root with its second @xmath189-derivative , and hence @xmath520 , @xmath521 . plugging this back into we see that @xmath522 . but @xmath523 so @xmath522 only for @xmath515 . hence for @xmath516 the point @xmath517 is a regular point of , that is , the algebraic equation is not branched at @xmath519 . we already observed that the simple zeros of @xmath518 are always branch points of multiplicity @xmath63 , so the riemann - hurwitz formula says that for @xmath516 the associated algebraic equation has genus @xmath217 . continuity with respect to @xmath510 assures that the genus can not increase for @xmath515 , and hence the genus is also zero for this value . the discussion above can be summarized in the following proposition : [ prop : algebraiccubic ] the algebraic equation with coefficients given by , and , has four branch points ( the zeros of the polynomial @xmath507 in ) and a double point ( the zero of @xmath512 in ) . two of the branch points are real and the other two form a complex conjugate pair . for @xmath524 all these points are distinct , while when @xmath525 , the double point and one of the real branch points of coalesce . the associated riemann surface has always genus @xmath217 . although the choice of @xmath73 in , as a root of @xmath494 instead of @xmath495 , was mostly motivated by the construction of a continuous one - parameter family of critical measures @xmath79 interpolating the extremal cases @xmath133 and @xmath24 studied in @xcite , formulas , and can also be explained in terms of the genus @xmath217 ansatz stated in theorem [ thm_genus_zero ] that we prove next . we already noted that if the riemann surface has genus @xmath217 , then @xmath73 must be a root of at least one of the polynomials @xmath494 and @xmath495 in , and proposition [ prop : algebraiccubic ] assures that the roots of @xmath494 give rise to genus @xmath217 riemann surfaces . it thus suffices to show that zeros of @xmath495 give rise to a surface of genus @xmath526 . consider @xmath73 to be a root of the polynomial @xmath495 . as before , @xmath73 can be assumed to be real , the remaining nonreal choices of @xmath73 as a root of @xmath495 can be reduced to the real ones with suitable change of variables . hence , @xmath527 making the change of variables @xmath528 , this can be written as @xmath529 where @xmath530 corresponds to the first value of @xmath73 in and @xmath531 corresponds to the second choice of @xmath73 in . with this identification , the discriminant @xmath488 simplifies to @xmath532 where @xmath533 the discriminant of @xmath534 is given by @xmath535 moreover , @xmath536 hence @xmath537 , unless @xmath538 , which corresponds to @xmath515 . but for this latter choice , the corresponding value of @xmath73 in coincides with the value of @xmath73 in , hence the coefficients @xmath61 and @xmath62 are given by . thus , let @xmath539 . then @xmath488 has four simple roots , which have to be branch points of the equation , and one double root @xmath540 . at this double root , the algebraic equation simply reduces to @xmath541 , so its three solutions coincide . this is only compatible with the fact that @xmath488 has a double root at @xmath540 if the three solutions are branched at this point . hence we have four branch points of multiplicity @xmath63 and one branch point of multiplicity @xmath153 , and the riemann - hurwitz formula gives us that the riemann surface has genus @xmath526 . the first part of theorem [ thm_genus_zero ] , claiming existence of @xmath41-critical measures , will be given by corollary [ corol_existence_critical_measure ] . [ rem : qdfordifferentc ] obviously the quadratic differential still makes sense if @xmath73 is a root of @xmath495 as in the proof above . numerical experiments performed to compute its critical graph indicate that the corresponding algebraic equation should also give rise to @xmath41-critical measures as in theorem [ thm_reciprocal_spectral_curve ] . in this section , starting from the algebraic equation @xmath542 where it is assumed that the coefficients @xmath61 and @xmath62 are given by , we find a vector of measures @xmath543 for which the respective @xmath189-functions in satisfy , and consequently we prove theorems [ thm_existence_critical_measures_cubic ] and [ thm_equilibrium_measure_cubic ] . a central object for this analysis is the associated quadratic differential ( see also below ) and its critical graph , whose description is postponed to section [ section : dynamics ] . according to proposition [ prop : algebraiccubic ] , the spectral curve has two real branch points @xmath221 , two non real branch points @xmath544 , with @xmath545 , and a double point @xmath546 since @xmath547 we easily conclude that @xmath548 for @xmath549 , with @xmath550 if and only if @xmath515 . moreover , equation defines a three - sheeted riemann surface @xmath551 of genus @xmath217 for every value of the parameter @xmath552 . in contrast to , where the cuts for the riemann surface are defined in terms of the supports of the critical measures , here the cuts that split @xmath551 into the sheets @xmath553 can be chosen in a somewhat arbitrary way , as long as they connect the branch points . in our case , the sheet structure will be given by two cuts : the interval of the real line connecting the real branch points @xmath554 of @xmath191 and a jordan arc ( to be defined precisely below ) that joins the complex - conjugate branch points @xmath234 . this arc intersects @xmath555 in a unique point @xmath242 , whose location depends on the value of the parameter @xmath510 . namely , there is a certain critical value @xmath556 , defined later , such that @xmath557 if and only if @xmath558 ( what we call the _ supercritical regime _ ) , see figure [ figure_sheet_structure ] . it is important to stress here that @xmath559 . obviously , it ultimately follows from our arguments that this cut structure coincides with for the critical measure given by theorem [ thm_existence_critical_measures_cubic ] . using these cuts we define three oriented sets , @xmath560 , @xmath561 and @xmath562 on @xmath26 . namely , @xmath561 is always the projection onto @xmath26 of the cut joining the complex - conjugate branch points @xmath234 and oriented from @xmath563 to @xmath222 . in the subcritical regime ( @xmath564 ) we denote by @xmath565\subset { \mathbb{r}}$ ] oriented from @xmath566 to @xmath567 , and set @xmath568 . in the supercritical regime ( @xmath558 ) , @xmath569\subset { \mathbb{r}}$ ] and @xmath570\subset { \mathbb{r}}$ ] , both with the natural orientation . the orientation induces the left ( denoted by the subscript `` @xmath159 '' ) and right ( with the subscript `` @xmath160 '' ) boundary values of functions defined on @xmath26 or @xmath551 . we define @xmath571 and build the riemann surface @xmath572 , associated to the algebraic equation , connecting each pair of sheets @xmath190 crosswise across the cuts as follows : @xmath560 connects @xmath444 with @xmath573 , @xmath561 connects @xmath444 with @xmath574 , and @xmath562 connects @xmath447 with @xmath574 ( this last condition is clearly non - trivial only in the supercritical regime , when @xmath558 ) , see again figure [ figure_sheet_structure ] . as we will see soon , the cuts @xmath575 can be specified in such a way that we will be able to define positive measures living on @xmath576 s , and the construction of the sheet structure will coincide with . the three solutions @xmath58 of are enumerated according to their asymptotic expansion at infinity : @xmath577 as before , the functions @xmath58 are regarded as branches of the same meromorphic function @xmath188 , defined by . as it is rigorously given by proposition [ proposition_distribution_branchpoints ] below , the function @xmath88 is the restriction of @xmath189 to the sheet @xmath190 of the riemann surface @xmath191 . figure_02a.pdf ( 170,140)@xmath578 ( 170,80)@xmath579 ( 170,20)@xmath580 ( 103,141)@xmath581 ( 55,119)@xmath582 ( 80,78)@xmath583 ( 126,78)@xmath584 ( 56,38)@xmath585 ( 31,7)@xmath586 figure_02b.pdf ( 100,141)@xmath581 ( 70,119)@xmath582 ( 65,27)@xmath587 ( 44,78)@xmath583 ( 123,78)@xmath584 ( 75,38)@xmath585 ( 49,7)@xmath586 ( 90,21)@xmath588 due to the explicit geometric description of the sets @xmath576 s and sheets @xmath190 s , it is straightforward to check that with @xmath589 @xmath193 extends as a single - valued meromorphic function on @xmath191 , and @xmath590 is the corresponding rational quadratic differential on @xmath191 . the details are also carried out in the general setting of theorem [ thm_quadratic_differential ] in its proof . one of the main outcomes of the discussion in section [ section : dynamics ] ( see theorem [ thm : criticaltraj ] and remark [ remark_orthogonal_trajectories ] ) is that we can choose the cut @xmath561 connecting @xmath234 to coincide with the trajectory along which @xmath591 furthermore , @xmath561 can be extended to an analytic arc @xmath272 from @xmath592 to @xmath593 in such a way that @xmath594 and @xmath595 see figure [ figure_geometry_support ] . figure_03.pdf ( 160,104)@xmath242 ( 85,104)@xmath566 ( 225,104)@xmath567 ( 130,150)@xmath222 ( 130,45)@xmath563 ( 145,125 ) ( 192.5,104 ) ( 122.5,104 ) ( 110,170)@xmath272 further , @xmath596 and @xmath597 and in the supercritical regime @xmath558 , also @xmath598 and @xmath599 for which we refer to proposition [ proposition_distribution_branchpoints ] . finally , it also holds @xmath600 and in the precritical regime @xmath601 , @xmath602 for which again we refer to proposition [ proposition_distribution_branchpoints ] . we define measures @xmath68 , @xmath69 , @xmath70 on @xmath560 , @xmath561 , @xmath562 , respectively , through the formulas @xmath603 \text{and } & \\ d\mu_3(s ) & = \begin{cases } 0 , & \text{if } 0<\tau<\tau_c , \\[1 mm ] \dfrac{1}{2\pi i}(\xi_{3+}(s)-\xi_{2+}(s))ds , \quad s\in \delta_3 , & \text{if } \tau_c<\tau<1/4 , \\ \end{cases } \end{split}\ ] ] where @xmath604 denotes the complex line element on the respective arc . due to their construction , the supports of the measures @xmath66 satisfy the claims of theorem [ thm_existence_critical_measures_cubic ] ( see also theorem [ thm : criticaltraj ] ) . using the definition in we can describe formulas saying that we build @xmath28 from the values of @xmath128 on the sheet @xmath605 , @xmath29 . expressions define positive measures @xmath68 , @xmath69 , @xmath70 . we prove the statement for the supercritical regime @xmath558 ; the precritical regime , somewhat simpler , can be analyzed similarly . from and it follows that the measures @xmath68 , @xmath69 , @xmath70 are real . moreover , the densities of @xmath68 , @xmath70 with respect to the complex line element @xmath604 are continuous and non vanishing in the interior of @xmath560 , @xmath562 , so the respective measures do not change sign . as for @xmath69 , its density with respect to @xmath604 is continuous when restricted to either the upper or the lower half plane , but not across @xmath555 . we start now with @xmath68 . for @xmath606 , we can write @xmath607)=-\frac{1}{2\pi i}\psi_{1+}(x),\ ] ] where @xmath608\cup \delta_2\right).\ ] ] by the asymptotic expansion , we have that @xmath609 and since @xmath610 does not change sign on @xmath611 , see , we conclude that @xmath612 the function @xmath613 vanishes at the point @xmath614 with order @xmath15 . since we already know that @xmath613 should map @xmath560 to @xmath615 , from its order of vanishing we further get that the imaginary part of @xmath616 is negative when @xmath617 is sufficiently close to the endpoint @xmath567 . from , we conclude @xmath618 by , this establishes the positivity of @xmath68 . furthermore , the density @xmath619 is the analytic continuation of @xmath620 across @xmath561 , hence @xmath621 is also positive . finally , in order to establish the sign of @xmath69 , consider first @xmath622 , @xmath623 . denote by @xmath624 $ ] the subarc of @xmath561 from @xmath563 to @xmath308 . then @xmath625)=\frac{1}{2\pi i}\psi_{2+}(x),\ ] ] where @xmath626\cup \delta_2).\ ] ] from and we learn that @xmath627 is monotone on @xmath628 . the asymptotics @xmath629 shows that @xmath630 hence @xmath631 is strictly decreasing on @xmath632 , @xmath633 . since @xmath634 vanishes with order @xmath15 on @xmath563 , we conclude that @xmath635 thus , by measure @xmath69 is positive on @xmath636 . the positivity of @xmath69 on @xmath637 can be obtained by similar arguments or using the real symmetry of the density of @xmath69 ; we leave the details to the interested reader . the proposition is proved . our next goal is an expression for the cauchy transforms of combinations of measures @xmath68 , @xmath69 , @xmath70 : [ prop_cauchy_transforms_cubic ] the cauchy transform of the measures @xmath68 , @xmath69 , @xmath70 defined in are related to the @xmath189-functions in through @xmath638 in particular , the total masses of the measures @xmath68 , @xmath69 , @xmath70 satisfy , namely @xmath639 this is a straightforward consequence of residues calculations . for instance , @xmath640 where the closed integral is computed along a contour oriented clockwise which encircles @xmath641 and does not encircle @xmath303 . analogously , @xmath642 and taking the difference of these last two equations , @xmath643 finally , is a direct consequence of the asymptotic expansion . a combination of proposition [ prop_cauchy_transforms_cubic ] with theorem [ thm_reciprocal_spectral_curve ] yields the first part of theorem [ thm_genus_zero ] , namely [ corol_existence_critical_measure ] the vector of measures @xmath644 defined through is @xmath41-critical for the potentials . recalling , the potential @xmath645 of a compactly supported signed measure @xmath12 for which @xmath646 is connected is the real part of a primitive of @xmath295 , that is @xmath647 where the constant is chosen so as to have @xmath648 let us apply this to the measures @xmath68 , @xmath69 , @xmath70 given in . from , @xmath649 and from , @xmath650 summarizing , @xmath651 where we must use the same paths of integration in the left and in the right hand sides . by we then conclude @xmath652 for some constant @xmath653 , the external field @xmath654 given in and @xmath655 . since the @xmath88 s have purely imaginary periods , the right hand side above is well defined regardless the path chosen . in a completely analogous way , we get @xmath656 combining with , we conclude that @xmath657 moreover , from the first equation in we also get @xmath658 furthermore , in the precritical case @xmath601 and @xmath659 , @xmath660 where for the second equality we used and for the final inequality we used . analogously , @xmath661 if @xmath662 , we evaluate , , at the common point @xmath663 and take differences in order to get @xmath664 on the other hand , if @xmath665 , we use to get @xmath666 we now combine this inequality with evaluated at @xmath667 and , and conclude @xmath668 hence , for both the precritical and supercritical cases we can define @xmath669 and with this definition , it follows that @xmath670 one more variational inequality is based on the fact that we deal with a critical trajectory of our quadratic differential . recall that by , @xmath671 where @xmath672 from , we know that @xmath634 is real - valued on @xmath673 . hence , @xmath674 moreover , by , the real - valued function @xmath634 is monotone on each connected component of @xmath673 . analyzing at @xmath195 , we see that @xmath675 hence @xmath634 tends to @xmath676 along @xmath272 . since it is zero at the endpoints @xmath563 , @xmath222 of the connected components of @xmath673 , we conclude that @xmath677 is always positive on @xmath673 , and hence @xmath678 we summarize our findings in the following theorem : [ thm_equilibrium_conditions_cubic ] let measures @xmath68 , @xmath69 , @xmath70 be defined in . then there exist real constants @xmath653 , @xmath679 and @xmath669 such that the following variational conditions are satisfied : @xmath680 where @xmath681 , @xmath682 , @xmath683 $ ] . [ rem_equilibrium_conditions_cubic ] in the pre - critical case ( @xmath601 ) , @xmath568 , thus the equality on @xmath562 in is void . the equalities in are the same as those in . the extra information in theorem [ thm_equilibrium_conditions_cubic ] is coming from the remaining equations , which assure that the triplet @xmath684 is the ( unique ) minimizer of the energy functional over measures @xmath685 satisfying ( with @xmath28 replaced by @xmath347 ) and @xmath686 , @xmath196 , see ( * ? ? ? * theorem 1.8 ) . this is equivalent to theorem [ thm_equilibrium_measure_cubic ] with @xmath687 . a natural first step in the study of the structure of the trajectories of a quadratic differential is to clarify the position and the character of its singular points . in the case of the quadratic differential we have to analyze the location and the dynamics of the branch points and the double point of the riemann surface @xmath551 ( corresponding to the spectral curve ) as functions of the parameter @xmath510 . recall that in section [ section_spectral_curve_to_variational_equations ] we have denoted the branch points of by @xmath688 and @xmath222 , with the conventions @xmath689 and the double point of by @xmath517 . [ proposition_description_branchpoints ] the main parameters of the riemann surface @xmath191 corresponding to the algebraic equation exhibit the following behavior : as @xmath510 grows from @xmath217 to @xmath690 , 1 . the coefficient @xmath73 in increases monotonically from @xmath691 to @xmath217 ; 2 . * the branch point @xmath566 decreases monotonically from @xmath692 to @xmath693 ; * the branch point @xmath567 increases monotonically from @xmath692 to @xmath694 ; * the double point @xmath517 increases monotonically from @xmath695 to @xmath676 . 3 . always @xmath696 and the equality is attained only for @xmath515 . recall that we chose @xmath73 in to be real , thus ( i ) follows directly from the definition of @xmath73 . any branch point @xmath697 of @xmath191 is a zero of the polynomial @xmath507 of degree @xmath698 and real coefficients , defined in , so that @xmath699 it is easy to check that the resultant of @xmath511 and @xmath700 ( with respect to the variable @xmath303 ) is @xmath701 which implies that for any root @xmath702 of @xmath507 , @xmath703 , and thus preserves its sign in the whole range of values of @xmath704 . on the other hand , since @xmath566 ( resp . , @xmath567 ) is the smallest ( resp . , largest ) real root of @xmath507 , and the leading coefficient of @xmath507 is positive , we know that @xmath705 straightforward calculations show that for @xmath706 , @xmath707 and @xmath708 in particular , @xmath709 , and we conclude that in this case , @xmath710 hence , @xmath711 for all @xmath704 , and by , @xmath566 is a decreasing and @xmath567 is an increasing function of @xmath510 . from the expression it follows that @xmath712 replacing it in we get @xmath713 since for @xmath482 , @xmath714 this concludes the proof of ( iii ) . finally , it remains to observe that for @xmath715 , @xmath716 which has one real positive root ( @xmath694 ) and two complex conjugate ones . this shows that @xmath717 we finish this section with a technical lemma that will be used later . [ prop_zeros_d ] for @xmath718 , the polynomial @xmath62 in does not have zeros on @xmath719 , whereas for @xmath720 , @xmath62 has exactly one zero on @xmath719 . moreover , for @xmath718 , @xmath721 only for @xmath515 , and @xmath722 is never zero . on one hand , the discriminant of the polynomial @xmath62 with respect to @xmath303 is @xmath723 which shows that for @xmath549 , polynomial @xmath62 has no multiple roots as long as @xmath516 . on the other hand , we have seen in section [ section_cubic_spectral_curve ] that the branch points of @xmath191 are the zeros of the polynomial @xmath507 defined in . the resultant ( also w.r.t . @xmath303 ) of @xmath62 and @xmath507 is @xmath724 so again , for @xmath549 , polynomials @xmath62 and @xmath507 have no common roots as long as @xmath516 , in particular implying that @xmath62 does not vanish at @xmath725 for @xmath516 . for @xmath515 , we compute @xmath726 and factor @xmath727 so for @xmath515 we have @xmath721 and @xmath728 . it is worth pointing out that both @xmath288 and @xmath2 can be easily found by means of any computer algebra software . having in mind that @xmath62 and @xmath507 do not share roots for @xmath516 , it is sufficient to establish the assertion concerning the zeros of @xmath62 for a single value of @xmath510 in @xmath729 , and for a single value of @xmath510 in @xmath730 . for @xmath715 , @xmath62 is a quadratic polynomial in @xmath731 so its roots can be explicitly computed ; we get that its only real roots are @xmath732 since @xmath733 from proposition [ proposition_description_branchpoints ] ( ii ) we see that for @xmath734 , for a certain small value of @xmath735 , @xmath736 on the other hand , it is easy to check that for @xmath482 , @xmath737 so that for @xmath738 , for a certain small value of @xmath735 , @xmath62 does not vanish on @xmath739 . in section [ section_spectral_curve_to_variational_equations ] we described the construction of the three - sheeted riemann surface @xmath740 and of the branch cuts in such a way that the three solutions @xmath88 of , specified by the asymptotic conditions , become meromorphic on the respective sheet @xmath190 , with poles only at @xmath741 . they are also pairwise distinct as long as @xmath488 , defined in , does not vanish , i.e. for @xmath742 . the arc @xmath561 intersects @xmath555 in a unique point @xmath242 ; there is a critical value @xmath743 , to be specified later , such that @xmath744 for @xmath745 ( what we called the precritical regime ) , and @xmath557 for @xmath558 ( the supercritical regime ) . as a first result we establish some relations between the solutions @xmath746 . [ proposition_distribution_branchpoints ] let @xmath704 , @xmath747 . then 1 . for @xmath748 , @xmath749 additionally , @xmath750 2 . on @xmath751 , * for @xmath752 , @xmath753 and @xmath754 * for @xmath755 , @xmath756 * for @xmath757 ( when @xmath758 ) , @xmath759 and @xmath760 + moreover , @xmath761 recall that we deal with the case @xmath261 , so that @xmath762 . the behavior at infinity in gives and also . furthermore , we have established in proposition [ proposition_description_branchpoints ] that if @xmath524 then @xmath763 , and in this case @xmath517 is a double zero of @xmath488 . this means that when @xmath524 , only two of the three values @xmath764 , @xmath765 , @xmath766 coincide , and since @xmath767 the coincident two differ in sign from the third one . furthermore , since also @xmath768 we see that the sign of this third one is opposite to the sign of @xmath769 . but direct calculations show that @xmath770 which means that for @xmath718 the two coincident values of @xmath771 are the largest two , and the other way around if @xmath772 . it remains to use in order to establish . inequalities follow by noticing that @xmath517 is a double zero of @xmath488 , so it is a simple zero of @xmath773 ( for @xmath774 ) and of @xmath775 ( for @xmath776 ) . from proposition [ prop_zeros_d ] we know that @xmath777 , @xmath778 for @xmath524 . in particular , since for @xmath482 ( see ) , @xmath779 and @xmath780 , we conclude that @xmath728 and @xmath781 for @xmath782 . in other words , the smallest two of the three solutions @xmath88 come together at @xmath566 and at @xmath567 . now implies for @xmath782 . on the other hand , recall that by proposition [ proposition_description_branchpoints ] , @xmath783 as @xmath784 , and that for @xmath715 , @xmath785 so that @xmath786 . using the same arguments we conclude that for @xmath720 , the largest two of the three solutions @xmath88 come together at @xmath567 ( and yields ) , and the smallest two become confluent at @xmath566 ( and follows from ) . the discriminant @xmath787 is negative for @xmath788 , so just one of the solutions @xmath88 is real on @xmath788 , and the other two are complex - conjugates of each other . since we have ruled out the coincidence of the three branches , equality implies that @xmath789 are non - real on @xmath790 , which yields . by the same argument we also have , as well as ( now using ) the identities . recall that we already established that the smallest two of the three solutions @xmath88 come together at @xmath566 , and shows that for @xmath601 , @xmath791 for @xmath601 , when crossing @xmath561 two of the three solutions @xmath88 are swapped , and the third one remains invariant . but the only option compatible both with and is . finally , for @xmath601 , the inequalities and show that @xmath134 is continuous across @xmath561 , and as a consequence has to hold , obviously for the full range of @xmath549 . this , in turn , implies the last identity . proposition [ proposition_description_branchpoints ] gives the formal proof of the fact that the riemann surface @xmath191 , described in section [ section_spectral_curve_to_variational_equations ] , is actually the riemann surface of the cubic equation , and with this construction the function @xmath88 is meromorphic on @xmath190 and satisfies the asymptotic expansion . moreover , @xmath792 , given by @xmath793 on @xmath190 , is meromorphic on @xmath191 , giving the global solution to the algebraic equation . from theorem [ thm_genus_zero ] , or alternatively proposition [ prop : algebraiccubic ] , the riemann surface @xmath191 has genus @xmath217 . let @xmath794 be the canonical projection on the riemann surface @xmath191 . for a point @xmath795 , we denote by @xmath796 , @xmath196 , its preimage by @xmath797 on @xmath190 , that is , @xmath798 this notation is trivially extended to @xmath799 by taking boundary values . notice that for the branch points it is valid @xmath800 and @xmath801 whereas if @xmath67 belongs to a cut connecting exactly two sheets , say @xmath190 and @xmath802 , then @xmath803 we insist that the construction of @xmath191 is independent of the concrete choice of the cut @xmath561 ; this freedom will be used latter to specify an appropriate @xmath561 . namely , in the next section we will show that @xmath561 can be made coincident with a critical trajectory of the quadratic differential @xmath197 , defined in , which connects @xmath563 and @xmath222 , see definition [ def : thebranchcut ] below . certain integrals of the function @xmath128 defined in will play a crucial role in the upcoming analysis of the dynamics of the trajectories of the quadratic differential @xmath804 on @xmath551 . they can be also formulated in terms of certain abelian integrals on @xmath551 . namely , we are interested in @xmath805 with @xmath806 defined for @xmath807 . in this definition we understand that we integrate between two points on a sheet @xmath808 along a path that stays entirely in @xmath808 . the values @xmath809 are correctly defined regardless of the precise choice of the integration paths . indeed , the residues of the functions @xmath58 at @xmath195 are real ( and independent of the value of @xmath510 ) , see , so the integral of @xmath128 along a big loop on either @xmath808 encircling @xmath810 is purely imaginary . it remains to notice that the genus of @xmath551 is zero , so that any closed contour around either branch cut @xmath576 can be deformed to such a big loop . analytic computation of @xmath809 s is a formidable task . instead , we have computed them numerically , see figure [ figure_width_parameters ] for the result . since the integrands in are multivalued functions , the numerical integration requires to implement an analytic continuation of each branch of @xmath189 . we give further details in the appendix [ appendix_numerics ] . figure_04.pdf ( 20,130)@xmath811 ( 20,60)@xmath812 ( 20,85)@xmath813 ( 157,60)@xmath814 ( 200,150)@xmath510 ( 100,155)@xmath815 ( 99,165)@xmath816 ( 148,167)@xmath815 ( 146,177)@xmath817 ( 175,155)@xmath815 ( 173,165)@xmath818 ( 72,155)@xmath815 ( 65,165)@xmath819 the functions @xmath820 , @xmath821 , have two and one zeros on @xmath822 , respectively , whereas @xmath823 and @xmath824 do not vanish on the intervals @xmath822 and @xmath825 , respectively . we denote the zeros of @xmath820 by @xmath826 and of @xmath821 by @xmath827 . we have @xmath828 so that they satisfy @xmath829 we point out that the value @xmath827 is the one used in section [ section_spectral_curve_to_variational_equations ] in the construction of the riemann surface @xmath191 , and it is equivalently determined by . it is also clear from figure [ figure_width_parameters ] that @xmath830 for @xmath831 . we follow the construction , and define the meromorphic quadratic differential @xmath804 on the riemann surface @xmath191 . we start by analyzing the character of the critical points of @xmath197 . for instance , the local parameter at @xmath832 is @xmath833 so that @xmath834 . in consequence , @xmath835 has a double zero at @xmath832 if and only if @xmath836 . a similar analysis at the rest of the points of @xmath551 yields the following classification of the critical points of @xmath197 on the riemann surface ( see figure [ figure_critical_points ] ) : a. for @xmath745 : a. simple zeros at @xmath837 , @xmath838 , @xmath839 , @xmath840 ; b. double zeros at @xmath841 , @xmath842 ( only for @xmath524 ) , @xmath843 , @xmath844 ; c. double zero at @xmath845 if @xmath846 and a double zero at @xmath847 if @xmath831 ; d. zero of order @xmath698 at @xmath848 if @xmath849 ; e. double pole at @xmath850 with a real residue ; f. poles of order @xmath851 at @xmath852 , @xmath853 . b. for @xmath854 : a. simple zeros at @xmath841 , @xmath838 , @xmath839 , @xmath840 ; b. double zeros at @xmath855 , @xmath842 , @xmath843 , @xmath844 ; c. double zero at @xmath847 ; d. double pole at @xmath850 with a real residue ; e. poles of order @xmath851 at @xmath852 , @xmath853 . 0.5 figure_05a.pdf 0.5 figure_05b.pdf 1 figure_05c.pdf it is instructive to think of the critical points as evolving dynamically with @xmath510 . under this perspective , propositions [ proposition_description_branchpoints ] and [ proposition_distribution_branchpoints ] show that for @xmath510 small the double point ( node ) @xmath517 corresponds to the double zero @xmath845 on the second sheet . when @xmath515 , the points @xmath517 , @xmath567 coalesce , giving rise to a higher order zero at the branch point @xmath856 . for larger values of @xmath510 , the double point emerges on the first sheet : now @xmath845 is a regular point whereas @xmath847 is a double zero . in the same spirit , the simple zero @xmath566 of the discriminant of carries two critical points of @xmath197 . for @xmath857 these are the simple zero @xmath837 and the double zero @xmath858 . for values of @xmath510 larger than @xmath827 , these points interchange their roles : @xmath841 is a simple zero and @xmath859 is a double zero . the rest of this section is devoted to the description of the critical graph of the quadratic differential for the whole range @xmath860 . one of the outcomes of our analysis is the following theorem : [ thm : criticaltraj ] for the quadratic differential @xmath861 and for all values of the parameter @xmath862 there exists a critical trajectory of @xmath197 joining @xmath839 and @xmath840 on @xmath863 , whose projection by @xmath797 on @xmath26 is a real - symmetric analytic arc @xmath561 joining @xmath563 and @xmath222 . for @xmath864 , there is an arc of critical trajectory of @xmath197 joining @xmath839 with a point @xmath865 on the interval @xmath866 $ ] which is determined by , and the conjugate symmetric arc of trajectory joining @xmath840 with the same point . the projection by @xmath797 on @xmath26 of the union of these two arcs of trajectories is also denoted by @xmath561 . recall that @xmath827 was formally introduced in section [ section_widths_cubic ] . in virtue of the results in section [ section_spectral_curve_to_variational_equations ] , in particular corollary [ corol_existence_critical_measure ] , theorem [ thm : criticaltraj ] implies theorem [ thm_existence_critical_measures_cubic ] . we remind the reader that up to now the branch cut , separating the sheets @xmath444 and @xmath574 , was free ( see figure [ figure_sheet_structure ] ) . in what follows we agree in the following : [ def : thebranchcut ] the curve , connecting @xmath563 and @xmath222 as part of the branch cut separating the sheets @xmath444 and @xmath574 , is always given by the lift of @xmath561 ( from theorem [ thm : criticaltraj ] ) to the sheets @xmath444 and @xmath574 . in the next sections we will show that this definition is consistent with our construction of the riemann surface @xmath191 . one important fact is that the residues of @xmath197 at the poles at infinity ( and the local behavior of the trajectories there ) are independent of @xmath510 : at @xmath850 they are closed analytic curves ( so that @xmath850 is the center of a circle domain , see appendix [ appendix_quadratic_differentials ] ) , while @xmath867 attract trajectories in 6 asymptotic directions , given by the angles @xmath868 critical values split the interval @xmath822 into the subintervals @xmath869 , @xmath870 , @xmath871 , @xmath872 and @xmath873 . we will show that the topology of the critical graph remains invariant in each of these intervals . the methodology we use can be summarized as follows : 1 . compute the critical graph for @xmath510 equal to one of the critical values . 2 . analyze the possible deformation of the trajectories for the values @xmath874 , with @xmath875 small , identifying the trajectories that display a phase transition . 3 . prove that the topology of the critical graph is invariant inside the subinterval of interest , by analyzing the behavior of the widths @xmath809 s and showing that the corresponding strip and ring domains can not disappear . along the way , will use some general _ principles _ that we enumerate here : 1 . quadratic differential @xmath197 has no recurrent trajectory for any value of @xmath510 , see jenkin s three poles theorem in section [ sec : globalstructuretrajectoriesappendix2 ] . if @xmath876 is an arc of trajectory of @xmath197 , then @xmath877 , corresponding to the lift of the complex conjugate of @xmath878 to the same sheet , is also an arc of trajectory . 3 . the complement of the critical graph of @xmath197 on @xmath191 can not have a simply connected component without poles on its boundary : that would contradict corollary [ corol_teichmuller_lemma ] or the maximum principle for harmonic functions on a compact riemann surface . 4 . the meromorphic function @xmath193 depends analytically on the parameter @xmath510 . hence the critical graph of @xmath197 , and in particular all its critical trajectories , depend continuously ( in any reasonable topology , for instance , in the hausdorff distance ) from @xmath510 . 5 . if for a certain value @xmath879 , the point @xmath67 belongs to the half plane domain for @xmath880 determined by the angles @xmath881 , then the same holds true for a small neighborhood of values @xmath882 , @xmath875 . the point @xmath67 is also allowed to depend continuously on @xmath510 . if for a certain value @xmath879 , an arc of trajectory emanating from a given point @xmath67 intersects the real line at a _ regular _ point , then the same holds true for @xmath882 , @xmath875 . as before , the point @xmath67 is allowed to depend continuously on @xmath510 . there will be one more useful tool that we will employ several times in our analysis , formulated as proposition [ lemma : zerosofd ] below . when describing the structure and the evolution of the trajectories of the quadratic differential @xmath197 we face the dilemma of either a formalization of each statement , with a precise formulation of the behavior of every trajectory in every situation , or a much more visual description , with rigorous proofs but illustrated by a number of figures . we opted for the second choice[multiblock footnote omitted ] . next , we agree on some convention about trajectories . let @xmath883 be a zero of @xmath197 . we denote by @xmath884 , @xmath885 , , the trajectories of @xmath197 _ emanating _ from @xmath67 _ on _ @xmath190 , in such a way that their canonical projections @xmath886 , see section [ sec : rsassociatedalgcurve ] , are enumerated in an anti - clockwise direction starting from the positive @xmath887 semiaxis . notice that when @xmath796 is a branch point of @xmath191 , so that @xmath888 for some @xmath889 , trajectories @xmath890 and @xmath891 are different because they emerge from @xmath888 on different sheets of @xmath191 otherwise , when @xmath796 belongs to a single sheet @xmath190 , we occasionally drop the superindex @xmath892 when it can not lead us into confusion . given two points @xmath893 , the integral @xmath894 along a contour @xmath876 connecting @xmath67 and @xmath534 is understood to be the integral of any analytic continuation of the meromorphic differential @xmath895 along @xmath876 . this is well defined up to the branch of the square root , which will be clear in each context . for @xmath482 , the algebraic equation reduces to @xmath896 whose solutions , denoted in accordance with , are @xmath897 where the branch of the square root is chosen to be positive for large real values , @xmath898 and the points @xmath899 are given explicitly by @xmath900 the cut @xmath560 is reduced to a single point @xmath566 , and the sheet @xmath447 is detached from the others . since is reducible , its riemann surface is in fact the union of two riemann surfaces , @xmath901 here @xmath902 , and @xmath561 is a simple curve connecting the points @xmath903 , to be precisely specified later . the quadratic differential degenerates into two quadratic differentials @xmath904 on @xmath905 and @xmath906 on @xmath907 , namely @xmath908 we analyze the structure of their critical graphs next . , whose only critical points are as follows : * simple zeros at @xmath909 ; * double zero at @xmath519 ; * pole of order @xmath851 at @xmath741 . under the change of variables @xmath910{3}}z$ ] , the quadratic differential @xmath904 becomes @xmath911 , where @xmath912 is , up to a multiplicative factor @xmath913 , the same polynomial obtained in ( * ? ? ? * eq . ( 2.1 ) ) . having in mind this identification , it was proven in ( * ? ? ? * theorem 2.1 ) that the trajectory @xmath914 of @xmath904 connects @xmath222 and @xmath563 : in the notation introduced above , @xmath915 , see figure [ alpha0_3 ] . from @xcite we also know that @xmath914 intersects the real axis at a point @xmath916 , which can be calculated numerically : by @xmath917 the rest of the critical graph of @xmath904 is as follows . notice that due to the symmetry , we only need to describe the trajectories in the upper half plane . figure_06.pdf ( 175,132)@xmath918 ( 110,132)@xmath919 ( 175,73)@xmath920 ( 110,73)@xmath921 ( 70,180)@xmath922 ( 10,168)@xmath923 ( 70,25)@xmath924 ( 10,40)@xmath925 ( 61,115)@xmath914 ( 65,78 ) @xmath563 ( 65,145 ) @xmath222 ( 122,92 ) @xmath517 the trajectories @xmath926 , @xmath927 , @xmath928 , can not be finite , see principle * p.3 * above . hence , they all diverge to @xmath195 along the asymptotic directions , and according theorem [ theorem_global_dissection ] , all directions are represented . there are 3 asymptotic directions for 4 trajectories in the upper half plane , so necessarily the divergence angle for @xmath918 is @xmath929 , while the divergence angle for @xmath923 is @xmath930 . since two consecutive trajectories emanating from a zero can not diverge to @xmath195 in the same direction ( this would contradict theorem [ teichmuller_lemma ] ) , we conclude that both @xmath919 and @xmath922 must diverge in the direction @xmath931 , see figure [ alpha0_3 ] . , whose only critical points are as follows : * double zeros at @xmath932 , @xmath933 and @xmath934 ; * double pole at @xmath935 with real residue ; * pole of order @xmath851 at @xmath853 . the double zeros @xmath936 @xmath937 are also branch points of @xmath907 , and the critical graph of @xmath906 is made of trajectories @xmath938 , @xmath939 , @xmath99 , emanating on @xmath444 , and of trajectories @xmath940 , @xmath941 , @xmath99 , along with @xmath942 , @xmath943 , emanating on @xmath574 , see figure [ alpha0_4_5 ] . the branch cut @xmath561 connecting the sheets @xmath444 and @xmath574 , so far arbitrary , is chosen as @xmath944 , where @xmath914 is the critical trajectory of @xmath904 connecting @xmath222 to @xmath563 , as described above . .5 figure_07a.pdf ( 45,135)@xmath945 ( -5,137)@xmath946 ( 45,10)@xmath947 ( -5,8)@xmath948 .5 figure_07b.pdf ( 46,140)@xmath949 ( -10,120)@xmath950 ( 120,85)@xmath951 ( 75,90)@xmath952 [ lemma : tau=0 ] with the branch cut @xmath561 specified above , the critical trajectories @xmath939 and @xmath938 of @xmath906 belong entirely to the sheet @xmath444 . suppose that one of the trajectories @xmath939 emanating from @xmath222 intersects the cut @xmath561 for the fist time at a point @xmath308 . clearly , this point ( actually , its canonical projection ) must lie in the upper half plane : otherwise we readily get that @xmath953 and no intersection with @xmath561 occur . integrating from @xmath222 to @xmath308 along @xmath939 and using the definition of a trajectory we get @xmath954 where the @xmath185 sign in the last integrand depends on the side of the cut @xmath561 to which @xmath308 belongs . however , @xmath561 projects onto the trajectory @xmath914 of @xmath904 , so the second integral in the right - hand side of is purely imaginary . hence , this equation reduces to @xmath955 it was proved in @xcite that the trajectory @xmath561 is contained in the domain bounded by the triangle with vertices @xmath222 , @xmath956 and @xmath563 . in particular , the part of @xmath561 on the upper half plane , and hence @xmath308 , is contained in the domain bounded by the triangle @xmath957 determined by the vertices @xmath222 , @xmath958 and @xmath956 . the function @xmath959 has a unique maximum on @xmath957 at the point @xmath960 . since @xmath961 is harmonic , it can not attain a maximum on the domain bounded by @xmath957 , hence can only occur if @xmath962 , showing that @xmath963 does not intersect the cut @xmath561 . recall that @xmath850 is the center of a circle domain , which means that all trajectories of @xmath906 passing through sufficiently distant points on @xmath444 are closed jordan curves . in particular , no trajectory diverges to @xmath850 , and every trajectory entirely contained in @xmath444 has to be closed . consequently , both trajectories @xmath939 are closed as well , @xmath953 , and @xmath945 ( respectively @xmath946 ) intersects the real line , say at the point @xmath964 ( respectively @xmath965 ) . we claim that @xmath966 with @xmath242 defined in . indeed , both @xmath964 and @xmath965 can not lie on the same side of the cut @xmath561 without running into contradiction with the general principle * p.3 * above . hence , either @xmath967 or @xmath968 . the latter is impossible without @xmath945 and @xmath946 intersecting somewhere in the upper half plane , which again contradicts * p.3*. we conclude that @xmath967 . let us prove the inequality @xmath969 . using the definition of trajectory and we get @xmath970 but @xmath971 , see figure [ figure_width_parameters ] , so that @xmath972 function @xmath775 is continuous and non - vanishing on @xmath973 , and by it is negative for large real parameters , so it is negative on the whole interval @xmath973 . since @xmath974 , the equality above is only possible if @xmath969 . this proves . [ cols= " < , < " , ] the discussion of the structure of the trajectories @xmath951 , @xmath952 , @xmath949 , @xmath950 is identical to the analysis of the trajectories @xmath926 , @xmath927 , @xmath928 , on @xmath447 for @xmath904 above , so we omit the details . the global structure of the critical graph on @xmath906 on both sheets is presented in figure [ alpha0_6_7 ] . the basic conclusion is that with the branch cut @xmath561 specified above , the critical graph splits into two sets : a closed jordan curve on @xmath444 , containing @xmath843 and @xmath975 , and 4 analytic arcs on @xmath574 , starting and ending at @xmath853 , each passing through one of the branch points @xmath976 , @xmath977 and @xmath837 . a combination of the general principles * p.2 * and * p.6 * assures us that the finite critical trajectories for @xmath482 remain finite for small perturbations of @xmath510 , and that the behavior of the trajectories described for @xmath482 is preserved for @xmath510 small . let @xmath875 be sufficiently small . the general principle * p.4 * above tells us that if we consider the domains @xmath978 , ( respectively @xmath979 and @xmath980 ) , swept by trajectories of passing through points in the @xmath981-neighborhood of @xmath841 ( respectively @xmath855 and @xmath837 ) , then there exists a @xmath982 such that the critical trajectories for @xmath197 and @xmath983 , passing through @xmath984 , @xmath29 , belong to @xmath985 . these domains are depicted schematically on figure [ figure_traj_strip_0_1 - 12 ] . .5 figure_09a.pdf ( 70,60)@xmath986 .5 figure_09d.pdf ( 70,60)@xmath986 .5 figure_09b.pdf ( 75,60)@xmath987 .5 figure_09e.pdf ( 80,60)@xmath987 .5 figure_09c.pdf ( 120,70)@xmath988 .5 figure_09f.pdf ( 120,68)@xmath988 we should keep in mind that the branch cut @xmath561 now is completely specified by definition [ def : thebranchcut ] , which is consistent as long as the critical trajectory @xmath989 joining @xmath839 and @xmath840 , _ exists _ and _ remains on @xmath447 _ for the full range of the parameter @xmath510 under consideration . the forthcoming analysis shows that this is the case for @xmath990 . according to the general principle * p.4 * , there exists a @xmath982 small enough such that for @xmath991 , both @xmath992 , @xmath29 , and the critical trajectories emerging from @xmath993 stay in @xmath994 . for instance , since for @xmath482 the critical trajectories @xmath942 , @xmath943 , define three half - plane domains ( bounded by @xmath995 , @xmath996 and @xmath997 , see figure [ alpha0_6_7 ] , right ) , they must be persistent under small perturbation of @xmath510 , and either @xmath837 or @xmath838 , or both , must belong to their boundaries . taking into account the structure of @xmath980 it is straightforward to conclude that for @xmath991 , the trajectories of @xmath197 through @xmath837 and @xmath838 are as shown in figure [ traj_final_0_tau_tau_1 ] . we now examine the trajectories from @xmath841 and @xmath842 . the following result comes in very handy : [ lemma : zerosofd ] let @xmath998 \displaystyle \int_{x } ^y \operatorname{re}(\xi_1(s)- \xi_{2+}(s ) ) \ , ds=\int_{x } ^y \operatorname{re}(\xi_1(s ) - \xi_{3+}(s))\ , ds , & \text{if } x , y \in \delta_3 , \end{cases}\ ] ] where we integrate along each interval . if @xmath999 , then there exists no pair of values @xmath1000 , @xmath1001 , such that @xmath1002 . if @xmath720 , and there exists a pair of values @xmath1000 , @xmath1001 ( resp . , @xmath1003 ) such that @xmath1002 , then there exists no such pair of values on @xmath562 ( resp . , on @xmath560 ) . furthermore , if @xmath1004 , @xmath1005 are two such pairs , @xmath1006 . notice that @xmath280 is well defined on @xmath560 and @xmath562 due to the symmetry relations and , and that @xmath568 for @xmath1007 . assume that there does exist a pair of values @xmath1008 , @xmath1001 , such that @xmath1002 ( same analysis is valid for @xmath1009 ) . by the mean value theorem , there exists a @xmath1010 such that @xmath1011 hence , @xmath1012 but @xmath1013 and the assertion follows from proposition [ prop_zeros_d ] , keeping in mind that @xmath62 has exactly one zero on @xmath1014 for @xmath720 . one of the consequences of proposition [ lemma : zerosofd ] is that for @xmath991 , the trajectories emanating from @xmath1015 and @xmath1016 can not cut @xmath560 and must stay on the sheet @xmath444 . thus , using again the general principle * p.4 * we conclude that the trajectories @xmath1017 , @xmath1018 , @xmath1019 , are closed and encircle the cut @xmath561 , see figure [ traj_final_0_tau_tau_1 ] . similar considerations can be applied to get the behavior for the trajectories emanating from @xmath855 , @xmath1020 , and the final result for @xmath510 small is seen in figure [ traj_final_0_tau_tau_1 ] . we skip the details . .5 figure_10a.pdf ( 18,40)@xmath1021 ( 33,40)@xmath1022 ( 77,50)@xmath1023 .5 figure_10b.pdf ( 52,40)@xmath1024 ( 77,50)@xmath1023 ( 77,25)@xmath1023 ( 105,40)@xmath1025 1 figure_10c.pdf ( 50,40)@xmath1022 the outcome of our analysis is that the critical graph of @xmath197 has the structure showed in figure [ traj_final_0_tau_tau_1 ] , at least for @xmath991 . our next goal is to prove that this is actually valid for @xmath1026 . the continuity principle * p.4 * yields that this is the case as long as 1 . no collision of the critical points occur : this is true indeed for @xmath1026 , see section [ section_critical_points ] . 2 . no new domains emerge , which amounts to say that the finite trajectories for @xmath991 remain critical for @xmath718 : this is assured by a combination of * p.2 * and * p.6*. 3 . no connected components of the complement of the critical graph `` disappear '' . more precisely , it means that no width of any strip or ring domain becomes zero . these domains for @xmath991 are identified on figure [ traj_final_0_tau_tau_1 ] : there is one ring domain @xmath1021 and 4 strip domains , @xmath1027 . there widths @xmath1028 ( see the definition in section [ sec : globalstructuretrajectoriesappendix2 ] ) are given by : * @xmath1029 , @xmath196 , as defined in . they do not vanish for @xmath1026 , see figure [ figure_width_parameters ] . * @xmath1030 , with @xmath280 defined in , which does not vanish for @xmath1026 , see proposition [ lemma : zerosofd ] . * @xmath1031 , which does not vanish for @xmath1026 , see . we conclude that the critical graph of @xmath197 , depicted in figure [ traj_final_0_tau_tau_1 ] , is valid for the whole range @xmath718 . in particular , the critical trajectory @xmath1032 connects the points @xmath839 and @xmath840 , which proves theorem [ thm : criticaltraj ] for @xmath718 . when @xmath515 , the double point @xmath517 coincides with @xmath567 , and the strip domain @xmath1025 disappears ( @xmath1033 as @xmath1034 ) , see figure [ figure_traj_strip_1 - 12_tau1 ] , left . clearly , this transition has no impact on the structure of trajectories on the third sheet . moreover , again a combination of * p.2 * and * p.6 * assures the finite trajectories for @xmath515 remain finite for @xmath1035 . let @xmath875 be sufficiently small . similarly to what has been done in the previous interval , the general principle * p.4 * tells us that if we consider the domains @xmath978 and @xmath979 , swept by trajectories of @xmath197 passing through points in the @xmath981-neighborhood of @xmath842 and @xmath1036 , then there exists a @xmath982 such that the critical trajectories for @xmath1037 , passing through @xmath1038 , @xmath99 , and @xmath847 , belong to @xmath1039 . these domains are also depicted schematically on figure [ figure_traj_strip_1 - 12_tau1 ] , left . .5 figure_11a.pdf .5 figure_11d.pdf .5 figure_11b.pdf .5 figure_11e.pdf .5 figure_11c.pdf .5 figure_11f.pdf for @xmath1037 we consider the first sheet and the trajectories emanating from @xmath842 and @xmath847 ; thanks to principle * p.2 * , we concentrate on the upper half plane @xmath1040 ( or to be precise , on its pre - image by @xmath797 on @xmath444 ) , namely @xmath1041 , @xmath1042 , @xmath1043 , see figure [ figure_traj_strip_1 - 12_tau1 ] , right . these trajectories must stay in @xmath1044 , so they have to intersect @xmath1045 on @xmath444 . let us denote the points of intersection of @xmath1041 , @xmath1042 , @xmath1043 by @xmath1046 , @xmath1047 , @xmath1048 , respectively . using the general principles * p.2 * and * p.3 * we must immediately discard the following possibilities : ( i ) @xmath1049 for some @xmath430 , ( ii ) @xmath1050 and @xmath1051 ( recall that @xmath1052 ) . since trajectories can not intersect , it holds @xmath1053 and we conclude that necessarily @xmath1054 , and consequently , @xmath1055 as well . in particular , @xmath1056 , in the notation . since @xmath1057 and @xmath1058 belong to trajectories with a common point @xmath847 , the assumption @xmath1059 yields that @xmath1060 , and since @xmath1061 , this contradicts proposition [ lemma : zerosofd ] . from the considerations above , it follows that @xmath1041 is closed , stays on @xmath444 , and intersects @xmath1045 to the left of @xmath561 , and the trajectories @xmath1042 , @xmath1043 intersect the cut @xmath560 and move to the second sheet @xmath447 . we keep denoting these points of intersection by @xmath1062 as before . clearly , @xmath1063 , and proposition [ lemma : zerosofd ] implies that these are the only points of intersection of these trajectories with the interval @xmath719 . let us turn to the second sheet , @xmath447 and consider @xmath1064 : from the structure of @xmath979 it is clear that it either diverges to @xmath852 , or intersects the branch cut between @xmath566 and @xmath567 and moves to @xmath444 . if we assume the latter , @xmath978 shows that either it will return to @xmath447 at a different point in @xmath719 ( in contradiction with proposition [ lemma : zerosofd ] ) , or it bounds a simply connected domain , which contradicts * p.3*. hence , @xmath1064 must diverge to @xmath852 , and thus @xmath1020 lies on the boundary of the half plane domain bounded for @xmath515 by @xmath1064 and @xmath1065 . in particular , by * p.5 * , for @xmath1035 , @xmath1064 diverges to @xmath852 in the same asymptotic direction given by the angle @xmath1066 from . .5 figure_12a.pdf ( 18,40)@xmath1021 ( 36,40)@xmath1022 ( 68,50)@xmath1023 ( 102,40)@xmath1025 .5 figure_12b.pdf ( 52,40)@xmath1024 ( 75,50)@xmath1025 ( 75,25)@xmath1025 ( 65,50)@xmath1023 ( 65,25)@xmath1023 1 figure_12c.pdf ( 53,40)@xmath1022 recall that we concluded that the trajectory @xmath1043 enters @xmath447 through the cut @xmath739 at a point @xmath1067 . the only possibility left for it is to go to @xmath852 . applying theorem [ teichmuller_lemma ] to the @xmath197-polygon bounded by the trajectories @xmath1043 and @xmath1068 , we get that @xmath1043 goes to @xmath852 in the asymptotic direction given by the angle @xmath1069 , and consequently @xmath1041 extends to @xmath852 with angle @xmath1070 as well . the outcome of our analysis is that for @xmath1035 the critical graph of @xmath197 has the structure showed in figure [ traj_final_1 - 12_to_tau1 ] . we prove that this is actually valid for @xmath1071 . again , the continuity principle * p.4 * yields that this is the case as long as ( i ) no collision of the critical points occur ( this is true indeed for @xmath1072 , see section [ section_critical_points ] ) , ( ii ) finite critical trajectories for @xmath1035 remain finite for @xmath1073 ( assured by a combination of * p.2 * and * p.6 * ) ; and ( iii ) no width of any strip and ring domains become zero . these domains for @xmath1035 are identified on figure [ traj_final_1 - 12_to_tau1 ] : there is one ring domain @xmath1021 and 4 strip domains , @xmath1074 . there widths @xmath1028 are given by : * @xmath1029 , @xmath196 , as defined in . they do not vanish for @xmath1073 , see figure [ figure_width_parameters ] , although @xmath1075 does vanish for @xmath1076 . * @xmath1077 is given by the absolute value of @xmath1078 and @xmath830 for @xmath831 , see figure [ figure_width_parameters ] in section [ section_widths_cubic ] . * @xmath1079 , which does not vanish for @xmath1080 , see . we conclude that the critical graph of @xmath197 , depicted in figure [ traj_final_1 - 12_to_tau1 ] , is valid for the whole range @xmath1073 . in particular this yields theorem [ thm : criticaltraj ] in the mentioned range of @xmath510 . .5 figure_13a.pdf .5 figure_13d.pdf .5 figure_13b.pdf .5 figure_13e.pdf .5 figure_13c.pdf .5 figure_13f.pdf at the value @xmath1076 the critical trajectory @xmath945 on the first sheet hits the branch point @xmath841 , so that the ring domain @xmath1021 disappears ( @xmath1081 as @xmath1082 ) , see figure [ traj_final_1 - 12_to_tau1 ] . from the analysis of the behavior of the rest of the widths @xmath1028 and the other finite critical trajectories , it follows that this fact does not affect the rest of the strip domains - note that there are no other ring domains . in particular , the trajectories emerging from @xmath566 , @xmath563 , and @xmath222 on the sheets @xmath447 , @xmath574 do not display any phase transition . the critical graph for @xmath1076 is depicted in figure [ figure_traj_strip_tau1_tauc ] . in accordance with the methodology we have followed so far , we fix an @xmath875 sufficiently small and consider the domain @xmath1044 swept by trajectories of @xmath197 passing through points in the @xmath981-neighborhood of @xmath844 and @xmath1083 . notice that @xmath1044 no longer lives on the single sheet , and its boundary now also contains critical trajectories , namely @xmath1084 , @xmath940 , @xmath941 , @xmath928 . this is so because , as already mentioned , there is no transition for these trajectories . observe also that when @xmath1085 the trajectory @xmath1086 does not collide with any critical point other than its endpoints , hence its topology is unchanged under small perturbations of @xmath510 around @xmath1087 . in fact , there exists a @xmath982 such that the critical trajectories for @xmath1088 , passing through @xmath842 , belong to @xmath1044 . this domain is also depicted schematically on figure [ figure_traj_strip_tau1_tauc ] , left . we now consider the possible behavior of @xmath945 for @xmath1088 , having in mind that it can not leave the shaded region @xmath1044 , which shows that either @xmath945 moves immediately to @xmath574 through @xmath561 , or it intersects the ( preimage of ) the real line near @xmath566 . in the first case , @xmath945 extends to @xmath853 with angle @xmath930 . thus @xmath1089 is the boundary of a @xmath197-polygon for which @xmath1090 and @xmath1091 , contradicting . assume otherwise , so that @xmath945 intersects the ( preimage of the ) real line at a point @xmath1092 , @xmath308 close to @xmath566 . if @xmath1093 , we integrate from @xmath222 to @xmath308 over @xmath945 and then from @xmath308 to @xmath566 over the real line to get @xmath1094 in the range of @xmath510 considered , @xmath1095 , while the last integral is @xmath1096 , see , which leads us into a contradiction . hence , @xmath1097 , so that @xmath945 moves to the second sheet . recall that if @xmath1048 is the point of intersection of @xmath1098 with @xmath560 , we already have @xmath1099 , so by proposition [ lemma : zerosofd ] , @xmath945 can not return to @xmath444 ; in consequence , it stays on the second sheet and diverges to @xmath852 in the asymptotic direction corresponding to the angle @xmath1069 , see figure [ figure_traj_prel2_tau1_to_tau_2 ] . .5 figure_14a.pdf .5 figure_14b.pdf on the other hand , trajectories @xmath1100 , @xmath928 , are `` trapped '' between @xmath945 and the branch cut @xmath1101 , see figure [ figure_traj_prel2_tau1_to_tau_2 ] , left . thus , they can not stay on @xmath444 without violating the general principle * p.3 * , so they move to the third sheet and diverge to @xmath853 in the asymptotic directions corresponding to the angles @xmath930 and @xmath1102 , respectively . the outcome of our analysis is that for @xmath1103 the critical graph of @xmath197 has the structure showed in figure [ traj_final_tau1_to_tauc ] . same analysis as in the previous section shows that this is actually valid for the whole range @xmath1104 , in particular implying theorem [ thm : criticaltraj ] for this range of @xmath510 . .5 figure_15a.pdf .5 figure_15b.pdf ( 56,55)@xmath1024 1 figure_15c.pdf we come to the topologically most important phase transition . according to definition [ def : thebranchcut ] , we use the lift of the trajectory joining @xmath839 and @xmath840 on @xmath447 as the branch cut connecting the sheets @xmath444 and @xmath574 . when @xmath1105 , the strip domain @xmath1024 disappears ( @xmath1106 as @xmath1107 ) , and this trajectory finally reaches the branch point @xmath855 , see figure [ traj_final_tau1_to_tauc ] . note that this transition corresponds to . we fix an @xmath875 sufficiently small and consider the domain @xmath1044 swept by trajectories of @xmath197 passing through points in the @xmath981-neighborhood of @xmath855 , @xmath839 , and @xmath840 . the critical graph for @xmath1105 along with @xmath1044 is displayed in figure [ traj_strip_tauc ] . .5 figure_16a.pdf .5 figure_16b.pdf 1 figure_16c.pdf for @xmath1108 we examine first the second sheet and the trajectories emanating from @xmath855 , @xmath839 , and @xmath840 . for a sufficiently small @xmath982 , these trajectories must stay in @xmath1044 , see figure [ figure_traj_prel1_tauc_tau2 ] . figure_17.pdf analyzing @xmath1109 we have to discard the following possibilities : * @xmath1109 can not intersect ( the preimage by @xmath797 of ) the real line to the left of @xmath566 without violating the general principle * p.3*. * it can not intersect ( the preimage by @xmath797 of ) the real line to on the cut @xmath719 either : otherwise the equation @xmath1110 has a solution in @xmath1111 , along with the identity @xmath1099 , where @xmath1048 is the point of intersection of @xmath1098 with @xmath560 , and since @xmath1112 , this would contradict proposition [ lemma : zerosofd ] . * @xmath1113 , because @xmath1114 for @xmath1115 , see figure [ figure_width_parameters ] . * @xmath1109 can not diverge to @xmath852 in the asymptotic direction @xmath931 . indeed , otherwise either @xmath989 also diverges to @xmath852 in the same direction , or it intersects the real axis to the left of @xmath855 . in the former case , we get a @xmath197-polygon for which @xmath1090 and @xmath1091 , contradicting , and in the latter one we proceed as in ( with @xmath820 replaced by @xmath821 ) to get a contradiction . the only possibility left for @xmath1109 is to diverge to @xmath852 in the asymptotic direction @xmath930 . since it was already observed that @xmath1116 can not diverge to @xmath852 , it must intersect @xmath1117 to the right of @xmath566 . the outcome of our analysis on the second sheet , as well as the region @xmath1044 on the remaining sheets , is displayed in figure [ figure_traj_prel2_tauc_to_tau2 ] . the cut @xmath561 is chosen in such a way that its projection on @xmath447 coincides with @xmath1118 . .5 figure_18a.pdf .5 figure_18b.pdf 1 figure_18c.pdf what is left is to describe the behavior of @xmath989 on the rest of the sheets . we already saw that this trajectory has to move to @xmath444 through the cut @xmath560 . it can not intersect @xmath560 again ( see proposition [ lemma : zerosofd ] ) , and it must stay in the region @xmath1044 displayed in figure [ figure_traj_prel2_tauc_to_tau2 ] . hence , the only possibility is that @xmath989 intersects the cut @xmath561 , moves to the sheet @xmath574 and diverges to @xmath853 in the asymptotic direction @xmath1102 . .5 figure_19a.pdf ( 30,40)@xmath1021 ( 64.5,43)@xmath1022 ( 64.5,34.5)@xmath1024 ( 80,65)@xmath1023 ( 112,40)@xmath1025 ( 58,57)@xmath1119 ( 58,20)@xmath1120 .5 figure_19b.pdf ( 60,55)@xmath1024 ( 60,20)@xmath1022 ( 40,55)@xmath1120 ( 40,20)@xmath1119 ( 75,50)@xmath1023 ( 75,25)@xmath1023 ( 86,50)@xmath1025 ( 86,25)@xmath1025 1 figure_19c.pdf ( 43,50)@xmath1119 ( 43,30)@xmath1120 ( 32,61)@xmath1022 ( 32,16)@xmath1024 ( 57,70)@xmath1021 ( 57,5)@xmath1021 the critical graph of @xmath197 for @xmath1121 has the structure showed in figure [ traj_final_tauc_to_tau2 ] , and we now prove that this is actually valid for @xmath1122 . again , the continuity principle * p.4 * yields that this is the case as long as ( i ) no collision of the critical points occur ( this is true indeed for @xmath1122 , see section [ section_critical_points ] ) ; ( ii ) finite trajectories for @xmath1121 remain finite for @xmath1123 ( assured by a combination of * p.2 * and * p.6 * ) and ( iii ) no width of any strip domains become zero . these domains for @xmath1121 are identified on figure [ traj_final_tauc_to_tau2 ] ; observe that there are now 7 strip domains @xmath1124 , and no ring domains . let us compute their widths @xmath1028 . [ lemmaaboutwidhts ] for @xmath1125 , @xmath1126 with @xmath1127 defined in . the fact that @xmath1128 is the straightforward consequence of the definition of @xmath820 . also @xmath1129 by the symmetry under conjugation . so , it remains to compute the width @xmath1130 , given by the absolute value of the real part of the integral @xmath1131 symmetry under conjugation tells us @xmath1132 and using it in the previous identity , we get @xmath1133 lemma [ lemmaaboutwidhts ] implies that @xmath1134 , @xmath29 , for @xmath1135 , although @xmath1136 as @xmath1137 , @xmath29 , see figure [ figure_width_parameters ] . regarding the rest of the strip domains , * @xmath1138 for @xmath1139 , see again figure [ figure_width_parameters ] . * @xmath1079 , which does not vanish for @xmath1080 , see . * from the symmetry by complex conjugation , @xmath1140 , and the structure of @xmath1120 on @xmath447 shows that @xmath1141 , so that @xmath1142 for @xmath1143 . consequently , the critical graph displayed in figure [ traj_final_tauc_to_tau2 ] is valid for @xmath1125 . in particular it implies theorem [ thm : criticaltraj ] for @xmath1144 . lemma [ lemmaaboutwidhts ] shows that at @xmath1145 , the strip domains @xmath1021 , @xmath1024 and @xmath1022 displayed in figure [ traj_final_tauc_to_tau2 ] disappear _ simultaneously _ , which happens because at that moment the branch point @xmath841 hits the critical trajectory @xmath1146 and the point @xmath242 of intersection of @xmath561 with the real line collides with the critical trajectories @xmath948 and @xmath945 . the resulting critical graph is shown in figure [ traj_strip_tau3 ] . as before , we fix an @xmath875 sufficiently small and consider the domain @xmath1044 swept by trajectories of @xmath197 passing through points in the @xmath981-neighborhood of @xmath841 , @xmath843 , @xmath844 and @xmath1147 . observe that for a small perturbation of @xmath1145 , @xmath1148 does not coalesce with critical points other than the starting point @xmath840 , hence this arc of critical trajectory displays the same structure as for @xmath1145 . in particular , the cut @xmath561 is well defined as the projection of @xmath1149 on the other sheets . thus , there exists a @xmath982 such that the critical trajectories for @xmath1150 , passing through the above mentioned critical points , belong to @xmath1044 . this domain is also depicted schematically on figure [ traj_strip_tau3 ] , left . .5 figure_20a.pdf .5 figure_20d.pdf .5 figure_20b.pdf .5 figure_20e.pdf .5 figure_20c.pdf .5 figure_20f.pdf [ lemma : zerocuvrelast ] let @xmath1151 be a point on the part of the curve @xmath1152 joining @xmath844 with @xmath1153 , and @xmath876 a jordan curve on @xmath444 connecting the boundary values @xmath1154 on @xmath1152 and containing the only branch point @xmath844 inside . then @xmath1155 we can deform @xmath876 to the cut @xmath561 . if we denote by @xmath1156 the arc of @xmath561 from @xmath222 to @xmath1151 , we get @xmath1157 where we have used the jump condition and the fact that @xmath1101 is an arc of trajectory of @xmath197 . now we describe the critical trajectories for @xmath1150 , starting with @xmath1158 . notice first that in this case @xmath1159 , so that @xmath1158 can not contain @xmath844 . furthermore , if @xmath1158 intersects the cut @xmath561 ( and thus diverges to @xmath852 in the asymptotic direction @xmath929 ) , then @xmath1160 determines a @xmath197-polygon for which @xmath1090 and @xmath1091 , in a contradiction with . keeping in mind that @xmath1158 must belong to @xmath1044 we conclude that it has to intersect the real axis in one of the sheets . let us denote by @xmath308 the point of the first intersection of this trajectory with @xmath1045 . again , we discard some cases : * @xmath308 can not be on @xmath444 to the left of @xmath566 : this yields ( by the general principle * p.2 * ) that @xmath1161 , violating * p.3*. * @xmath308 can not be on @xmath444 to the right of @xmath242 . + indeed , if @xmath1162 , we form a curve @xmath876 given by the union of three pieces : @xmath241 is the arc of @xmath1163 from @xmath1153 to @xmath841 , @xmath243 is the arc of @xmath1158 from @xmath841 to @xmath308 , and @xmath1164 is the interval from @xmath308 to @xmath1153 . this curve satisfies the assumptions of lemma [ lemma : zerocuvrelast ] , so that @xmath1165 since @xmath1166 by the definition of trajectories , we conclude that @xmath1167 that is , @xmath1168 , in the notation . but if @xmath1048 is the point of intersection of @xmath1098 with @xmath560 , we also have @xmath1099 , and since @xmath1169 , this would contradict proposition [ lemma : zerosofd ] . * @xmath308 can not be on @xmath447 to the left of @xmath242 ( in other words , @xmath308 can not belong to @xmath562 , which could occur if the trajectory @xmath1158 had slipped to the second sheet through the cut @xmath561 before hitting the real line ) : this yields @xmath1170 that is , @xmath1171 , in the notation , with @xmath1172 . but if @xmath1048 is the point of intersection of @xmath1098 with @xmath560 , we also have @xmath1099 , in contradiction with proposition [ lemma : zerosofd ] . the only possibility left is that @xmath1158 hits the real line _ precisely _ at the point @xmath242 . this means also that @xmath1173 , as shown in figure [ traj_final_tau2_1 - 4 ] . regarding the trajectories @xmath945 and @xmath946 , they can not satisfy @xmath1174 , and due to principle * p.3 * they must belong to @xmath1044 . hence , they have to behave as shown in figure [ traj_final_tau2_1 - 4 ] . we skip the details . .5 figure_21a.pdf ( 30,46)@xmath1021 ( 30,30)@xmath1024 ( 55,60)@xmath1022 ( 55,15)@xmath1023 ( 80,65)@xmath1120 ( 112,40)@xmath1025 .5 figure_21b.pdf ( 63,55)@xmath1120 ( 63,20)@xmath1120 ( 40,55)@xmath1024 ( 40,20)@xmath1021 ( 25,57)@xmath1023 ( 25,20)@xmath1022 ( 86,50)@xmath1025 ( 86,25)@xmath1025 1 figure_21c.pdf ( 50,43)@xmath1021 ( 50,34)@xmath1024 ( 32,55)@xmath1022 ( 32,20)@xmath1023 ( 95,45)@xmath1021 ( 95,32)@xmath1024 the critical graph of @xmath197 for @xmath1175 has the structure showed in figure [ traj_final_tau2_1 - 4 ] , and we prove that this is actually valid for @xmath1176 . the continuity principle * p.4 * yields that this is the case as long as ( i ) no collision of the critical points occur ( this is true indeed for @xmath1176 , see section [ section_critical_points ] ) , ( ii ) the finite critical trajectories for @xmath1175 remain finite in the range @xmath1177 ( certainly true by a combination of * p.2 * and * p.6 * ) and ( iii ) no width of any strip domains become zero . these domains for @xmath1175 are identified on figure [ traj_final_tau2_1 - 4 ] ; observe that there are now 6 strip domains @xmath1124 , and no ring domains . their widths @xmath1028 are : * @xmath1178 for @xmath1176 . * @xmath1179 for @xmath1176 . * @xmath1079 , which does not vanish for @xmath1080 , see . * as in , we get that @xmath1180 , and @xmath830 for @xmath831 , see figure [ figure_width_parameters ] in section [ section_widths_cubic ] . we conclude that the structure of the critical graph of @xmath197 , depicted in figure [ traj_final_tau2_1 - 4 ] , is actually valid for the whole range @xmath1176 . this finishes the proof of theorem [ thm : criticaltraj ] . the attentive reader might notice that in figure [ traj_final_tauc_to_tau2 ] , for instance , the critical trajectories @xmath1032 and @xmath1158 intersect the cut @xmath561 in @xmath444 on pairs of opposite points @xmath1181 . this phenomenon , which also occurs in figure [ traj_final_tau2_1 - 4 ] , is easily explained by lemma [ lemma : zerocuvrelast ] . [ remark_orthogonal_trajectories ] it follows from the results of sections [ section_trajectories_0_tau_1][section_trajectories_tau2_1 - 4 ] that the trajectories @xmath1182 and @xmath1183 determine a half plane domain @xmath1184 . in particular , this implies that there is an orthogonal critical trajectory @xmath241 emerging from @xmath840 which is entirely contained in @xmath1184 and extends to @xmath852 along the angle @xmath1185 . similarly , there is an orthogonal critical trajectory @xmath243 ( which is the complex conjugate of @xmath241 ) emerging from @xmath839 and extending to @xmath852 along the angle @xmath1186 . then the projected contour @xmath1187 satisfies the conditions stated in . the proof of theorem [ thm_reciprocal_spectral_curve ] presented in section [ section_general_variational ] is valid when the set @xmath1188 of double poles of the coefficient @xmath62 in is empty ( see proposition [ lemma_variations_without_double_poles ] ) . our goal now is to show that for a vector of measures @xmath350 whose components are supported on a finite union of analytic arcs , and such the associated functions @xmath88 in satisfy for a polynomial @xmath61 and a rational function @xmath62 , the equality @xmath1189 is valid for every function @xmath36 , without any further restriction on the poles of @xmath62 . recall that this fact was established so far for the cauchy kernels @xmath298 defined in , and when @xmath1190 , see proposition [ lemma_variations_without_double_poles ] . as a first step , we extend to polynomials : [ lemma_variations_polynomial ] under the assumptions of theorem [ thm_reciprocal_spectral_curve ] , @xmath1191 for every algebraic polynomial @xmath534 . fix @xmath1192 for which @xmath1193 for @xmath1194 and @xmath303 sufficiently large , we can expand @xmath1195 which implies the identity @xmath1196 where the function @xmath1197 converges to @xmath217 as @xmath89 uniformly for @xmath1194 , and @xmath1198 is a polynomial of degree @xmath1199 in @xmath308 , given explicitly by @xmath1200 set @xmath1201 . if @xmath1202 is a polynomial of degree @xmath1203 , then shows that @xmath1204 where @xmath1205 note that @xmath128 is a polynomial of degree @xmath1206 in @xmath308 . moreover , @xmath1207 and @xmath1208 both converge to @xmath217 as @xmath342 uniformly for @xmath1194 . hence , the convergences @xmath1209 hold uniformly for @xmath1210 , and from the definition of @xmath1211 in we get @xmath1212 the quantity @xmath278 is linear in @xmath280 , so implies @xmath1213 where for the last equality we used corollary [ corollary_converse_critical_measure ] , and hence from the previous limit we get @xmath1214 the result now follows easily by induction on the degree @xmath1203 of @xmath534 . if @xmath1215 , then @xmath1216 is identically zero , and the equality above implies that @xmath1217 . assuming now that @xmath359 for every polynomial @xmath280 of degree at most @xmath1206 , we get that @xmath1218 because @xmath1219 is a polynomial of degree at most @xmath1206 in @xmath308 , and the equality above implies @xmath1191 , concluding the proof . if @xmath1220 , then as it is discussed in remark [ remark : angelesco - nikishin ] , the point @xmath67 belongs to exactly two of the supports of @xmath68 , @xmath69 and @xmath70 , and locally the union of these sets is an analytic arc . that is , there exists an open disk @xmath1221 centered at @xmath67 such that @xmath1222 is an analytic arc passing through @xmath67 . additionally , given any point @xmath1223 , there exists a small disk @xmath1224 centered @xmath303 , disjoint from @xmath358 and such that the set @xmath1225 is a finite union of analytic arcs , which can only intersect at the common point @xmath303 . in case @xmath1226 , this intersection reduces to a single analytic arc . the collection @xmath1227 constructed above is an open cover of the compact set @xmath279 , from which we extract a finite subcover @xmath1228 where for @xmath1229 we have @xmath1230 for some @xmath1231 . set @xmath1232 it follows from their construction that these sets satisfy @xmath1233 consider a smooth partition of unity @xmath1234 of @xmath279 subordinated to the open cover @xmath1235 . that is , each function @xmath1236 is real , belongs to @xmath1237 and additionally satisfies the following properties . * @xmath1238 , for every @xmath39 . * for every @xmath74 , @xmath1239 or @xmath1240 . * every @xmath1241 belongs to the support of a finite number of functions in the collection @xmath1234 . * @xmath1242 , for every @xmath1241 . since @xmath279 is compact , the collection @xmath1234 can be assumed to be finite . moreover , we can refine @xmath1234 and assume that @xmath1239 whenever @xmath1243 . set @xmath1244 the functions @xmath1245 and @xmath1246 belong to @xmath1237 , satisfy @xmath1247 and @xmath1248 [ lemma_variations_polynomial_local ] under the conditions of theorem [ thm_reciprocal_spectral_curve ] , if @xmath534 is a polynomial , then @xmath1249 , where @xmath1246 is the function constructed above . from , it follows that @xmath1250 on @xmath279 . from the definition of @xmath1251 in we then get @xmath1252 using the first condition in , we get @xmath1253 , so lemma [ lemma_variations_without_double_poles ] gives us @xmath1254 . since @xmath534 is a polynomial , we learn from lemma [ lemma_variations_polynomial ] that @xmath1191 , concluding the proof . we are finally able to prove theorem [ thm_reciprocal_spectral_curve ] in its full generality . recall the definition of the arcs @xmath1255 , @xmath1220 , given in . each of these arcs is a simple contour on the complex plane , and we can find a smooth arc @xmath1256 for which @xmath1257 and @xmath1258 is connected . in particular , the second condition in implies @xmath1259 consider a parametrization @xmath1260\to { \mathbb{c}}$ ] of @xmath876 by arc length , set @xmath1261 and define a continuous function @xmath1262 by @xmath1263 . that is , @xmath1264 is a unit vector tangent to @xmath876 at the point @xmath303 , varying continuously with @xmath303 . given @xmath36 , define @xmath1265 @xmath876 is a simple smooth arc , so it has empty interior . since @xmath1258 is connected and @xmath1266 is continuous , mergelyan s theorem tells us that there exists a sequence of polynomials @xmath1267 converging to @xmath1266 uniformly on @xmath876 . in particular , for @xmath1268 this implies that the convergence @xmath1269 holds uniformly on @xmath876 , and as a consequence the sequence of polynomials @xmath1270 converges to @xmath1271 uniformly for @xmath1272 . in summary , we constructed a sequence of polynomials @xmath1273 converging uniformly to @xmath280 on @xmath876 , and for which the sequence of derivatives @xmath1274 converges to @xmath1266 uniformly on @xmath876 ; in particular there exists @xmath1275 , independent of @xmath1276 , such that @xmath1277 hence , the convergence @xmath1278 holds true uniformly along @xmath876 . due to , this is enough to conclude that the convergence above holds uniformly on @xmath279 , so that @xmath1279 the measures @xmath322 and @xmath70 do not have point masses , so the diagonal @xmath1280 has zero @xmath1281 measure . thus the limit also implies that the convergence @xmath1282 holds true pointwise @xmath1283-a.e . since the arc @xmath876 is connected , we also know that @xmath1284 } \left| \frac{d}{dt}\left ( \left((\widehat \psi q_n ) \circ \gamma \right)(t ) \right ) \right|_{t = s}\ ] ] whenever @xmath1285 . in virtue of and , the right - hand side in the inequality above is uniformly bounded in @xmath1276 . hence the left - hand side of is uniformly bounded along @xmath876 , and using and once again , we can extend this conclusion to @xmath279 . using the dominated convergence theorem and we conclude @xmath1286 for @xmath1287 . combined with , we finally get @xmath1288 from lemma [ lemma_variations_polynomial_local ] , we know that @xmath1289 for every @xmath1276 , hence @xmath1290 . on the other hand , due to the first condition in , we have @xmath1291 , so from lemma [ lemma_variations_without_double_poles ] we get @xmath1292 . thus , @xmath1293 where for the first equality we used . since @xmath36 is arbitrary , corollary [ corollary_critical_measure ] gives us that the measure @xmath79 is critical , concluding the proof . a meromorphic quadratic differential @xmath197 on a riemann surface @xmath191 is a differential form of type @xmath1294 , given locally by an expression @xmath1295 , where @xmath288 is a meromorphic function of a local coordinate @xmath303 . if @xmath1296 is a conformal change of variables , then @xmath1297 represents @xmath197 in the local coordinates @xmath702 . in this appendix , we sketch the minimal background on quadratic differentials used throughout the paper . the general references are the monographs by strebel @xcite and jenkins @xcite ; some additional information can be found in @xcite . the _ critical _ or _ singular points _ of @xmath1298 are the zeros and poles of @xmath288 ; recall that a zero ( resp . , a pole ) of @xmath197 is a point @xmath67 where in a local chart sending @xmath67 to @xmath217 we have @xmath1299 , with @xmath1300 , and with the integer @xmath1301 ( resp . , @xmath1302 ) . the value @xmath1276 is the _ order _ of the critical point @xmath67 , and is denoted by @xmath1303 . the rest of the points of @xmath191 are called regular , and their order is assumed to be @xmath1304 . critical points of order @xmath1305 ( i.e. , poles of order 2 and higher ) are called _ infinite _ , and the rest of the critical points are _ finite_. in a neighborhood of any regular point @xmath67 , the primitive @xmath1306 is well defined by specifying the branch of the square root at @xmath67 and continuing it analytically along the path of integration . function @xmath1307 provides a _ distinguished _ or a _ natural _ parameter on @xmath191 in a neighborhood of @xmath67 . we are mostly interested in the _ trajectories _ of a quadratic differential @xmath197 . a jordan arc @xmath1308 is called an _ arc of trajectory _ of @xmath197 if it is locally mapped by @xmath108 to a vertical line . more precisely , this means that for any point @xmath1309 , there exists a neighborhood @xmath1310 where the primitive @xmath108 above is well defined and satisfies @xmath1311 a maximal arc of trajectory is called a _ trajectory _ of @xmath197 . analogously , the _ orthogonal trajectories _ of @xmath197 are trajectories of @xmath1312 ; they can be equivalently defined by replacing `` @xmath1313 '' by `` @xmath1314 '' in . a trajectory @xmath876 extending to a finite critical point along at least one of its directions is called _ critical _ ; in the case when it happens in both directions , we call this trajectory _ bounded _ ( also _ finite _ or _ short _ ) , and _ unbounded _ ( or _ infinite _ ) otherwise . notice that both ends of a short trajectory may coincide , in which case it forms a loop on @xmath191 . @xmath197-chain _ is a connected set on @xmath191 made of a finite union of arcs of trajectories or orthogonal trajectories of @xmath197 . if no curves in a @xmath197-chain belong to orthogonal trajectories , we refer to it as a _ path of trajectories _ of @xmath197 ( or a _ @xmath197-path _ ) . in this case , in order to avoid the trivial situation , two consecutive arcs of a @xmath197-path are required to intersect at a singular point of @xmath197 . the local behavior of trajectories of a meromorphic quadratic differential @xmath197 is well understood . from a point @xmath67 of order @xmath1315 emanate @xmath1316 trajectories , forming equal angles @xmath1317 at @xmath67 . this covers also regular points , meaning that through any regular point passes exactly one trajectory , which is locally an analytic arc ( see figure [ figure_traj_locally_1 ] ) . .33 figure_22a.pdf .33 figure_22b.pdf 0.33 figure_22c.pdf an infinite critical point @xmath67 or order @xmath1318 has a neighborhood @xmath1266 with the following property : there are @xmath1319 asymptotic directions , henceforth called _ critical directions _ , forming equal angles @xmath1320 at @xmath67 , such that each trajectory entering @xmath1266 stays in @xmath1266 and tends to @xmath67 in one of the critical directions ( * ? ? ? * theorem 3.3 ) . if a trajectory is fully contained in @xmath1266 , then it tends to @xmath67 in two consecutive critical directions ( see figure [ figure_traj_locally_2 ] ) . .5 figure_23a.pdf .5 figure_23b.pdf at a double pole @xmath67 there are three possibilities . for @xmath1321 , we define the _ residue _ @xmath73 of @xmath197 at @xmath198 to be the residue of @xmath1322 at @xmath198 , which is well defined up to a sign . if @xmath1323 then there are no trajectories emanating from @xmath67 and the trajectories near @xmath67 are closed loops . if @xmath1324 , then there are trajectories emanating from @xmath73 in every direction . in the rest of the cases , the trajectories near @xmath67 converge to @xmath67 in a spiral form ( see figure [ figure_traj_locally_3 ] ) . .33 figure_24a.pdf .33 figure_24b.pdf 0.33 figure_24c.pdf there are three possible behaviors for a trajectory @xmath876 in the large , a. @xmath876 is a closed curve containing no critical points . b. @xmath876 is an arc connecting two critical points ( which may coincide ; in this case @xmath876 is a closed curve ) . c. @xmath876 is an arc that has no limit along at least one of its directions . trajectories satisfying _ ( ii ) _ are called _ short _ or _ finite_. trajectories satisfying ( iii ) are called _ recurrent _ , and they are usually a major source of troubles when studying the global structure of trajectories of a given quadratic differential . fortunately ( for us ) in this paper we deal with quadratic differentials with at most @xmath153 poles on a genus @xmath217 compact riemann surface , and the absence of recurrent trajectories in this case is assured by jenkin s three poles theorem ( * ? ? ? 8.5 , page 226 ) . it is intuitively clear that a non - recurrent and non - closed trajectory @xmath876 has two limiting ( extremal ) values when we travel it in both opposite directions , and that can be distinct or equal . for convenience , we will denote these extremal values by @xmath1325 and @xmath1326 . for instance , for a short trajectory @xmath876 both @xmath1325 and @xmath1326 are finite critical points . the set of the critical trajectories of a quadratic differential @xmath197 ( together with their limit points , i.e. the critical points of @xmath197 ) is the _ critical graph _ of @xmath197 , denoted by @xmath1327 . according to ( * ? ? ? * theorem 3.5 ) ( see also @xcite ) , the complement of the closure of @xmath1328 in @xmath191 consists of a finite number of domains called the _ domain configuration _ of @xmath197 . the knowledge of @xmath1329 ( or of the domain configuration of @xmath197 ) is sufficient to fully understand the global structure of trajectories of @xmath197 , as evidenced by the following theorem : [ theorem_global_dissection ] let @xmath197 be a meromorphic quadratic differential on a compact riemann surface @xmath191 . suppose in addition that @xmath197 has no recurrent trajectories . then @xmath1330 decomposes into a finite union of disjoint domains @xmath1331 , each of them bounded by a finite number of critical trajectories . each domain @xmath1332 lies into one of the following four classes . 1 . * half plane * ( or * end * ) * domain * : it is swept by trajectories converging to a pole @xmath67 of order @xmath81 in its two ends , and along consecutive critical directions . its boundary consists of a @xmath197-path with two unbounded critical trajectories and a finite number of short trajectories . for some choice of the branch of the square root , the natural parameter @xmath108 in is a conformal map from @xmath1332 to a vertical half plane @xmath1333 for some @xmath1323 , and it extends continuously to the boundary of @xmath1332 with the identification @xmath1334 . * strip domain * : it is swept by trajectories which both ends tend to poles @xmath67 , @xmath534 of order @xmath1335 , possibly with @xmath1336 . the boundary @xmath1337 is a disjoint union of two @xmath197-paths , each of them consisting of two unbounded critical trajectories converging to @xmath67 and @xmath534 , and possibly a finite number of short trajectories . + for some real constants @xmath1338 , @xmath108 maps @xmath1332 conformally to a vertical strip @xmath1339 and it extends continuously to the boundary of @xmath1332 , with appropriate identification of the points @xmath1340 with the directions @xmath1341 . * ring domain * : it is swept by closed trajectories . its boundary consists of two connected components , where each of them is a closed @xmath197-path . for a suitably chosen real constant @xmath73 and some real numbers @xmath1342 , the function @xmath1343 maps @xmath1332 conformally to an annulus @xmath1344 and it extends continuously to the boundary of @xmath1332 . * circle domain * : it is swept by closed trajectories and contains exactly one double pole , with purely real residue . its boundary is a closed @xmath197-path . + for a suitably chosen real constant @xmath73 and some real number @xmath291 , the function @xmath1343 is a conformal map from @xmath1332 to the circle centered at origin and radius @xmath82 ; it extends continuously to @xmath1345 and sends the double pole to the origin @xmath1346 . in case @xmath197 has also recurrent trajectories , a fifth class of domains has to be added to the domain configuration of @xmath197 ; we refer the reader to @xcite for further details . for a given short trajectory @xmath876 connecting two finite critical points @xmath67 , @xmath534 ( which coincide if @xmath876 is closed ) we define its _ length _ by @xmath1347 the _ width of a strip domain _ @xmath1348 is defined as @xmath1349 , where the constants @xmath1350 are as in . alternatively , it can be computed as @xmath1351 where we integrate along any path in @xmath1348 connecting two points , @xmath67 and @xmath534 , lying on different connected components of @xmath1352 . in the same spirit , the _ width of a ring domain _ @xmath1332 is defined as @xmath1353 where @xmath1354 and @xmath73 are as in , and we integrate along any path in @xmath1332 connecting two points , @xmath67 and @xmath534 , lying on different connected components of its boundary . for any open simply connected domain @xmath1355 bounded by a @xmath197-chain ( that is called a _ @xmath197-polygon _ ) we define two values : the total order of the singular points of @xmath197 in @xmath1332 is @xmath1356 where the summation is along all the singular points @xmath1357 of @xmath197 in @xmath1332 , while the contribution from the singular points of @xmath197 on the boundary is @xmath1358 where the summation is along all the corners @xmath1357 of @xmath1359 , @xmath1360 and @xmath1361 is the inner angle ( in radians ) at the corner @xmath67 . both values have a simple relation , as shown by the following simple consequence of the argument principle ( also known as the teichmller lemma , see ( * ? ? ? * theorem 14.1 ) ) : [ teichmuller_lemma ] if @xmath1332 is a @xmath197-polygon , then @xmath1362 a straightforward corollary of this lemma ( and also a direct consequence of the maximum principle for holomorphic functions ) is the following fact : [ corol_teichmuller_lemma ] if @xmath197 is analytic ( has no poles ) in a @xmath197-polygon @xmath1332 , then @xmath1359 must contain at least one pole of @xmath197 . this corollary is also the basis for the general principle * p.3 * in section [ sec : generalprinciples ] . in this appendix we look under the hood of the calculation of the functions @xmath809 in , as well as of the numerical procedures used to find and plot the trajectories of the quadratic differential @xmath197 from section [ section : dynamics ] . as it was mentioned , figure [ figure_width_parameters ] was obtained by means of a numerical evaluation of the integrals defining the functions @xmath809 in . for that , we compute the integrals of the form @xmath1363 along the line segment joining chosen roots @xmath1364 , @xmath1365 of the discriminant in by means of the composite trapezoidal rule . for @xmath510 fixed , we compute the points @xmath1366 , choose a value @xmath1367 , and consider a grid of @xmath1368 equally spaced nodes @xmath1369 , @xmath1370 that will be used as the quadrature nodes for the composite trapezoidal rule . at each @xmath1371 we solve numerically , obtaining an ( unordered ) set of three solutions @xmath1372 . comparing their values at consecutive quadrature points , we collect them into a sequence of ( ordered ) vectors @xmath1373 , @xmath1374 , where @xmath1375 is a permutation of @xmath1376 that does not depend on @xmath430 . we can then determine the permutation @xmath1375 using [ coinciding_nodes , xi_at_branchpoints1,xi_at_branchpoints2,xi_at_branchpoints3,xi_at_branchpoints4 ] as boundary conditions . this procedure is repeated for @xmath1276 equally spaced values of @xmath510 , @xmath1377 ( notice that @xmath1378 ; we stop at @xmath1379 in order to avoid the degenerate situation at @xmath715 for which some of the endpoints of integration diverge to @xmath195 ) . the result of these calculations with @xmath1380 and @xmath1381 is plotted in figure [ figure_width_parameters ] . on the other hand , we also performed numerical experiments that helped us to build the intuition to predict ( and confirm ) the structure of the critical graphs in section [ section : dynamics ] . a sample of such graphs is presented in [ numerics_critical_graph_1,numerics_critical_graph_2,numerics_critical_graph_3 ] . 0.33 figure_25a.pdf 0.33 figure_25b.pdf 0.33 figure_25c.pdf 0.33 figure_26a.pdf 0.33 figure_26b.pdf 0.33 figure_26c.pdf 0.33 figure_27a.pdf 0.33 figure_27b.pdf 0.33 figure_27c.pdf the numerical procedure used for these pictures is as follows . if @xmath1382 is a parameterization of a trajectory of @xmath1383 , then @xmath1384 where @xmath288 is some real valued function . a different choice of @xmath288 correspond just to a reparameterization of @xmath876 . in a natural ( arc - length ) parametrization of @xmath876 the equation above takes the form @xmath1385 this is an ordinary differential equation for @xmath876 that can be solved by standard methods ( e.g. the family of runge - kutta algorithms ) . we should bewared of two aspects when implementing this method . the first one concerns the initial values , that usually are at branch points of , and thus , at zeros of @xmath128 , from where more than one trajectory emanates . this can be resolved by perturbing the initial point along the prescribed direction , which can be obtained from a local analysis of @xmath128 at the singular point . the second aspect concerns the choice of branches of @xmath193 in , where we take advantage of the fact that all the branch points of are quadratic . the value of @xmath193 is found numerically by solving , which gives us the three possible values @xmath1386 . near a branch point two of these values are close ( corresponding to the two solutions coinciding at this branch point ) , allowing us to distinguish the third solution . this , in turn , allows to recognize on the the possible branches of @xmath193 , but not the other two . for instance , at @xmath960 we will have @xmath1387 ( see ) , which singles out the branch @xmath134 and makes the branch @xmath1388 easily distinguishable . in order to identify the remaining two branches ( i.e. , @xmath1389 and @xmath1390 ) we must use further results about the local and global structure of the critical graph of @xmath197 , established in section [ section : dynamics ] . part of this work was carried out during our visit to the department of mathematics of the vanderbilt university , usa , as well as during a stay of the first author as a visiting chair professor at the department of mathematics of the shanghai jiao tong university ( sjtu ) , china . we gratefully acknowledge the hospitality and the work environment of the host institutions . we also thank l. zhang for explaining his article @xcite , which was our starting motivation , e. a. rakhmanov for his interest , and a.b.j . kuijlaars for a careful reading of the first version of this manuscript and for his useful suggestions . in particular , we give him credit for the example [ example_arno ] . the first author was partially supported by the spanish government together with the european regional development fund ( erdf ) under grants mtm2011 - 28952-c02 - 01 ( from micinn ) and mtm2014 - 53963-p ( from mineco ) , by junta de andaluca ( the excellence grant p11-fqm-7276 and the research group fqm-229 ) , and by campus de excelencia internacional del mar ( ceimar ) of the university of almera . the second author was supported by fwo flanders projects g.0641.11 and g.0934.13 . g. lvarez , l. martnez - alonso and e. medina _ determination of @xmath1-curves with applications to the theory of non - hermitian orthogonal polynomials _ , j. stat . theory exp . 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saddle points of a vector logarithmic energy with a vector polynomial external field on the plane constitute the _ vector - valued critical measures _ , a notion that finds a natural motivation in several branches of analysis . we study in depth the case of measures @xmath0 when the mutual interaction comprises both attracting and repelling forces . for arbitrary vector polynomial external fields we establish general structural results about critical measures , such as their characterization in terms of an algebraic equation solved by an appropriate combination of their cauchy transforms , and the symmetry properties ( or the @xmath1-properties ) exhibited by such measures . in consequence , we conclude that vector - valued critical measures are supported on a finite number of analytic arcs , that are trajectories of a quadratic differential globally defined on a three - sheeted riemann surface . the complete description of the so - called critical graph for such a differential is the key to the construction of the critical measures . we illustrate these connections studying in depth a one - parameter family of critical measures under the action of a cubic external field . this choice is motivated by the asymptotic analysis of a family of ( non - hermitian ) multiple orthogonal polynomials , that is subject of a forthcoming paper . here we compute explicitly the riemann surface and the corresponding quadratic differential , and analyze the dynamics of its critical graph as a function of the parameter , giving a detailed description of the occurring phase transitions . when projected back to the complex plane , this construction gives us the complete family of vector - valued critical measures , that in this context turn out to be vector - valued equilibrium measures .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Federal Reserve Credit Facility Review Act of 2009''. SEC. 2. FINDINGS. The Congress finds as follows: (1) In August 2007, liquidity abruptly dried up in credit and securities markets. (2) This lack of access to affordable credit was initially limited to financial firms with interests in mortgage-backed securities that contained subprime and predatory mortgages. (3) The lack of access to credit quickly spread throughout the financial services industry, and eventually worldwide. (4) At the inception of the financial crisis, the Board of Governors of the Federal Reserve System responded by exercising its authorities in the traditional manner to effect the Federal funds rate target, which culminated in a December 16, 2008, decision to establish a Federal funds rate target range of 0 percent to 0.25 percent. (5) The Board of Governors of the Federal Reserve System, as it employed its traditional tools to provide liquidity and stability to the financial markets, came to acknowledge the severity of the current crisis by exercising its authority to act in response to ``unusual and exigent circumstances''. (6) The Federal Reserve has exercised its authority to address ``unusual and exigent circumstances'' no less than 11 times since the beginning of the financial crisis. (7) Before this financial crisis, the Board of Governors of the Federal Reserve System last exercised its authority to address ``unusual and exigent circumstances'' in 1934. (8) In connection with the Board of Governors of the Federal Reserve System's efforts to address unusual and exigent circumstances, the Board extended assistance to nonmember institutions, something it had not done since 1959. (9) In connection with the Board of Governors of the Federal Reserve System's efforts to address unusual and exigent circumstances, the Board has purchased debt obligations from government-sponsored enterprises, something it had not done since 1981. (10) In the course of the crisis, the Federal Reserve established joint programs with the Department of the Treasury to aid financial markets, such as the guarantee of Citigroup's and Bank of America's assets, the Term Asset-Backed Securities Lending Facility, and the Public-Private Partnership Investment Program. (11) On February 10, 2009, Chairman Ben Bernanke affirmed his commitment to transparency when he testified to the Committee on Financial Services of the House of Representatives that ``the Federal Reserve is committed to keeping the Congress and the public informed about its lending programs and balance sheet''. SEC. 3. REVIEWS OF SPECIAL FEDERAL RESERVE CREDIT FACILITIES. Section 714 of title 31, United States Code, is amended by adding at the end the following new subsection: ``(e) Reviews of Credit Facilities of the Federal Reserve System.-- ``(1) In general.--Subject to paragraph (3) and notwithstanding any limitation in subsection (b) on the auditing and overseeing of certain functions of the Board of Governors of the Federal Reserve System or any Federal reserve bank, the Comptroller General may conduct reviews, including onsite examinations when the Comptroller General determines such actions are appropriate, of credit facilities established by the Board or any Federal reserve bank, and of the establishment of such credit facilities by the Board or any Federal reserve bank-- ``(A) in carrying out any action or function approved by the Board under the 3rd undesignated paragraph of section 13 of the Federal Reserve Act (12 U.S.C. 343) as the lender of last resort; or ``(B) in providing temporary assistance to private institutions as the lender of last resort. ``(2) Description.--As of the date of the enactment of the Federal Reserve Credit Facility Review Act of 2009, the credit facilities to which this subsection applies include the following: ``(A) Money Market Investor Funding Facility. ``(B) Asset-Backed Commercial Paper Money Market Mutual Fund Liquidity Facility. ``(C) Term Asset-Backed Securities Loan Facility. ``(D) Term Auction Facility. ``(E) The Primary Dealer Credit Facility. ``(F) The Commercial Paper Funding Facility. ``(G) The Term Securities Lending Facility, including the Term Securities Lending Facility Options Program ``(H) Maiden Lane, LLC. ``(I) Maiden Lane II, LLC. ``(J) Maiden Lane III, LLC. ``(K) The Revolving Credit Facility. ``(L) Reciprocal currency arrangements with foreign central banks. ``(M) Mortgage Backed Securities Purchase Program, as well as the purchase of debt obligations from a Government Sponsored Enterprise. ``(N) Any special purpose vehicle through which any such credit facility conducts any activity or lending. ``(3) Termination of authority.--Paragraph (1) shall cease to apply after the expiration of the 5-year period beginning on the date of the enactment of this subsection. ``(4) Report.-- ``(A) Required.--A report on each review conducted under paragraph (1) shall be submitted by the Comptroller General to the Congress before the end of the 90-day period beginning on the date on which such review is completed. ``(B) Contents.--The report under subparagraph (A) shall include a detailed description of the findings and conclusion of the Comptroller General with respect to the review that is the subject of the report, together with such recommendations for legislative or administrative action as the Comptroller General may determine to be appropriate.''. SEC. 4. ACCESS TO RECORDS. (a) Access to Records.--Section 714(d)(1) of title 31, United States Code, is amended-- (1) in the first sentence, by inserting ``or any credit facility established by an agency'' after ``an agency''; and (2) by inserting after the first sentence the following: ``The Comptroller General shall have access to the officers, employees, contractors, and other agents and representatives of any agency or any credit facility established by an agency (as specified in subsection (e)) at any reasonable time as the Comptroller General may request. The Comptroller General may make and retain copies of such records as the Comptroller General determines appropriate.''. (b) Unauthorized Access.--Section 714(d)(2) of title 31, United States Code, is amended-- (1) by inserting ``, copies of any records,'' after ``records''; and (2) by inserting ``or any credit facility established by an agency (as specified in subsection (e))'' after ``agency''.

Federal Reserve Credit Facility Review Act of 2009 - Authorizes the Comptroller General to conduct reviews, including onsite examinations, of any credit facility established by the Federal Reserve Board or any federal reserve bank, and of its establishment as the lender of last resort, including when it provides temporary assistance to private institutions as the lender of last restort. Specifies the credit facilities to which this Act applies. Terminates such authorization five years after the enactment of this Act. Grants the Comptroller General access to all records and property of any such credit facility, as well as to its officers, employees, contractors, and other agents and representatives.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Mental Health Parity Act of 1996''. SEC. 2. PLAN PROTECTIONS FOR INDIVIDUALS WITH A MENTAL ILLNESS. (a) Permissible Coverage Limits Under a Group Health Plan.-- (1) Aggregate lifetime limits.-- (A) In general.--With respect to a group health plan offered by a health insurance issuer, that applies an aggregate lifetime limit to plan payments for medical or surgical services covered under the plan, if such plan also provides a mental health benefit such plan shall-- (i) include plan payments made for mental health services under the plan in such aggregate lifetime limit; or (ii) establish a separate aggregate lifetime limit applicable to plan payments for mental health services under which the dollar amount of such limit (with respect to mental health services) is equal to or greater than the dollar amount of the aggregate lifetime limit on plan payments for medical or surgical services. (B) No lifetime limit.--With respect to a group health plan offered by a health insurance issuer, that does not apply an aggregate lifetime limit to plan payments for medical or surgical services covered under the plan, such plan may not apply an aggregate lifetime limit to plan payments for mental health services covered under the plan. (2) Annual limits.-- (A) In general.--With respect to a group health plan offered by a health insurance issuer, that applies an annual limit to plan payments for medical or surgical services covered under the plan, if such plan also provides a mental health benefit such plan shall-- (i) include plan payments made for mental health services under the plan in such annual limit; or (ii) establish a separate annual limit applicable to plan payments for mental health services under which the dollar amount of such limit (with respect to mental health services) is equal to or greater than the dollar amount of the annual limit on plan payments for medical or surgical services. (B) No annual limit.--With respect to a group health plan offered by a health insurance issuer, that does not apply an annual limit to plan payments for medical or surgical services covered under the plan, such plan may not apply an annual limit to plan payments for mental health services covered under the plan. (b) Rule of Construction.-- (1) In general.--Nothing in this section shall be construed as prohibiting a group health plan offered by a health insurance issuer, from-- (A) utilizing other forms of cost containment not prohibited under subsection (a); or (B) applying requirements that make distinctions between acute care and chronic care. (2) Nonapplicability.--This section shall not apply to-- (A) substance abuse or chemical dependency benefits; or (B) health benefits or health plans paid for under title XVIII or XIX of the Social Security Act. (3) State law.--Nothing in this section shall be construed to preempt any State law that provides for greater parity with respect to mental health benefits than that required under this section. (c) Small Employer Exemption.-- (1) In general.--This section shall not apply to plans maintained by employers that employ less than 26 employees. (2) Application of certain rules in determination of employer size.--For purposes of this subsection-- (A) Application of aggregation rule for employers.--All persons treated as a single employer under subsection (b), (c), (m), or (o) of section 414 of the Internal Revenue Code of 1986 shall be treated as 1 employer. (B) Employers not in existence in preceding year.-- In the case of an employer which was not in existence throughout the preceding calendar year, the determination of whether such employer is a small employer shall be based on the average number of employees that it is reasonably expected such employer will employ on business days in the current calendar year. (C) Predecessors.--Any reference in this subsection to an employer shall include a reference to any predecessor of such employer. SEC. 3. DEFINITIONS. For purposes of this Act: (1) Group health plan.-- (A) In general.--The term ``group health plan'' means an employee welfare benefit plan (as defined in section 3(1) of the Employee Retirement Income Security Act of 1974) to the extent that the plan provides medical care (as defined in paragraph (2)) and including items and services paid for as medical care) to employees or their dependents (as defined under the terms of the plan) directly or through insurance, reimbursement, or otherwise. (B) Medical care.--The term ``medical care'' means amounts paid for-- (i) the diagnosis, cure, mitigation, treatment, or prevention of disease, or amounts paid for the purpose of affecting any structure or function of the body, (ii) amounts paid for transportation primarily for and essential to medical care referred to in clause (i), and (iii) amounts paid for insurance covering medical care referred to in clauses (i) and (ii). (2) Health insurance coverage.--The term ``health insurance coverage'' means benefits consisting of medical care (provided directly, through insurance or reimbursement, or otherwise and including items and services paid for as medical care) under any hospital or medical service policy or certificate, hospital or medical service plan contract, or health maintenance organization contract offered by a health insurance issuer. (3) Health insurance issuer.--The term ``health insurance issuer'' means an insurance company, insurance service, or insurance organization (including a health maintenance organization, as defined in paragraph (4)) which is licensed to engage in the business of insurance in a State and which is subject to State law which regulates insurance (within the meaning of section 514(b)(2) of the Employee Retirement Income Security Act of 1974), and includes a plan sponsor described in section 3(16)(B) of the Employee Retirement Income Security Act of 1974 in the case of a group health plan which is an employee welfare benefit plan (as defined in section 3(1) of such Act). Such term does not include a group health plan. (4) Health maintenance organization.--The term ``health maintenance organization'' means-- (A) a federally qualified health maintenance organization (as defined in section 1301(a) of the Public Health Service Act), (B) an organization recognized under State law as a health maintenance organization, or (C) a similar organization regulated under State law for solvency in the same manner and to the same extent as such a health maintenance organization. (5) State.--The term ``State'' means each of the several States, the District of Columbia, Puerto Rico, the Virgin Islands, Guam, American Samoa, and the Northern Mariana Islands. SEC. 4. SUNSET. Section 2 shall cease to be effective on September 30, 2001. SEC. 5. FEDERAL EMPLOYEE HEALTH BENEFIT PROGRAM. For the Federal Employee Health Benefit Program, sections 2 and 3 will take effect on October 1, 1997. SEC. 6. EXEMPTION. Notwithstanding the provisions of this Act, if the provisions of this Act result in a 1 percent or greater increase in the cost of a group health plan's premiums, the purchaser is exempt from the provisions of this Act.

Mental Health Parity Act of 1996 - Requires a group health plan that applies an aggregate lifetime (or annual) limit for medical or surgical services, if the plan also provides a mental health benefit, to include mental health payments in that limit or establish a separate aggregate lifetime (or annual) limit for mental health services, with the mental health limit not less than the medical or surgical limit. Prohibits a group health plan that does not apply a medical or surgical limit from applying a mental health limit. Exempts employers with fewer than 26 employees. Makes this Act ineffective after September 30, 2001. Exempts a purchaser from this Act if the Act's provisions result in a one percent or greater increase in the cost of a group health plan's premiums.

SECTION 1. SHORT TITLE. This Act may be cited as the ``FAMS Augmentation Act of 2010''. SEC. 2. INCREASE IN THE NUMBER OF FEDERAL AIR MARSHALS. (a) Increase in Number of Federal Air Marshals.--Not later than September 30, 2012, and in accordance with subsection (b), the Assistant Secretary (Transportation Security Administration) shall increase the number of Federal air marshals so that not less than 1,750 additional Federal air marshals are hired and deployed, above the number of such marshals as of January 31, 2010, to ensure increased transportation security for inbound international flights. (b) Congressional Intent.--The goal of this Act is to increase the number of inbound flights with Federal air marshals onboard while maintaining Federal air marshal presence on domestic point-to-point flights at or above the level as of December 25, 2009. SEC. 3. TRAINING OF FEDERAL AIR MARSHALS. Section 44917 of title 49, United States Code, is amended by adding at the end the following: ``(e) Criminal Investigative Training Program.-- ``(1) New employee training.--Not later than 30 days after the date of enactment of the FAMS Augmentation Act of 2010, the Federal Air Marshal Service shall establish a policy requiring Federal air marshals hired after such date to complete the criminal investigative training program at the Federal Law Enforcement Training Center as part of basic training for Federal air marshals. ``(2) Existing employees.--A Federal air marshal who has previously completed the criminal investigative training program may not be required to repeat such program. ``(3) Alternative training.--Not later than 3 years after the date of enactment of the FAMS Augmentation Act of 2010, an air marshal hired before such date who has not completed the criminal investigative training program shall be required to attend an alternative training program, as determined by the Director of the Federal Law Enforcement Center, that provides the training necessary to bridge the gap between the mixed basic police training, the Federal air marshal programs already completed by the Federal air marshal, and the criminal investigative training provided through the criminal investigative training program. Any such alternative program shall be deemed to have met the standards of the criminal investigative training program. ``(4) Reservation of funds.--Of the amounts to be appropriated pursuant to section 6 of the FAMS Augmentation Act of 2010, $3,000,000 may be used to carry out this subsection for each of fiscal years 2011 and 2012. ``(5) Savings clause.--Nothing in this subsection shall be construed to reclassify Federal air marshals as criminal investigators.''. SEC. 4. OMBUDSMAN. Section 44917 of title 49, United States Code, is further amended by adding at the end the following: ``(f) Ombudsman.-- ``(1) Establishment.--The Assistant Secretary shall establish in the Federal Air Marshal Service an Office of the Ombudsman. ``(2) Appointment.--The head of the Office shall be the Ombudsman, who shall be appointed by the Assistant Secretary. ``(3) Duties.--The Ombudsman shall carry out programs and activities to improve morale, training, and quality of life issues in the Service, including through implementation of the recommendations of the Inspector General of the Department of Homeland Security and the Comptroller General. ``(4) Career reserved position.--The position of Ombudsman shall be treated as a career reserved position, as defined by section 3132(a)(8) of title 5, United States Code. ``(5) Reservation of funds.--Of the amounts to be appropriated pursuant to section 6 of the FAMS Augmentation Act of 2010, $1,000,000 may be used to carry out this subsection for each of fiscal years 2011 and 2012.''. SEC. 5. REPORTS. (a) Reports.--Beginning on December 31st of 2010 and every 6 months thereafter, until the Department has increased, by not less than an additional 1,750, the number of Federal air marshals the Assistant Secretary shall submit a report to the Committee on Homeland Security of the House of Representatives and the Committee on Commerce, Science, and Transportation of the Senate on the progress of increasing the number of Federal air marshals under this Act, adopting the alternative criminal investigative training program, and implementing an ombudsman program for such marshals. (b) Report Summary.--The report shall include a summary of disciplinary personnel actions implemented against Federal air marshals by the Department of Homeland Security and complaints and lawsuits filed by Federal air marshals against the Department or its agents. SEC. 6. AUTHORIZATION OF APPROPRIATIONS. There are authorized to be appropriated to carry out this Act and subsections (d) and (e) of section 44917 of title 49, United States Code, $190,000,000 for fiscal year 2011 and $172,000,000 for fiscal year 2012.

FAMS Augmentation Act of 2010 - Directs the Assistant Secretary of Homeland Security (DHS) for the Transportation Security Administration (TSA) to increase the number of federal air marshals by at least an additional 1,750 above the number of such marshals as of January 31, 2010, to ensure increased transportation security for inbound international flights. Declares the goal of this Act is to increase the number of inbound flights with federal marshals onboard while maintaining federal marshal presence on domestic point-to-point flights at or above December 25, 2009, levels. Directs the Federal Air Marshal Service (FAMS) to establish a policy requiring newly hired federal air marshals to complete as part of their basic training the criminal investigative training program at the Federal Law Enforcement Training Center. Requires federal air marshals hired before enactment of this Act who have not completed such program to attend an alternative training program. Directs the Assistant Secretary to establish in FAMS an Office of the Ombudsman.

pulmonary hypertension ( ph ) is a disease characterized by increased pulmonary artery pressure ( pap ) due to increased pulmonary vascular resistance ( pvr ) and/or large intracardiac or vascular left - to - right shunts ( transfer of systemic pressures to the right side of the heart and pulmonary artery ) . ph increases right ventricular pressure and may lead to heart failure , disability and finally , death of the patient in most cases . ph can be idiopathic or secondary to other known diseases . the newest classification of ph , known as dana point classification , categorized this disease into 5 main subclasses . these include pulmonary arterial hypertension ( pah ) , ph owing to left heart diseases , ph owing to lung diseases and/or hypoxia , chronic thromboembolic ph ( cteph ) , and ph with unclear multifactorial mechanisms . in 1958 , heath and edward presented a pathological classification of ph into 6 progressive grades : i ( retention of fetal type pulmonary vessels , ii ( medial hypertrophy with cellular intimal reaction ) , iii ( progressive fibrous vascular occlusion ) , iv ( progressive generalized arterial dilatation with the formation of complex dilatation lesions ; plexiform lesions ) , v ( chronic dilation with formation of numerous dilation lesions and pulmonary hemosiderosis ) , and vi ( necrotizing arteritis ) . although ph is not generally regarded as an inflammatory disease , there are evidences that inflammation plays a great role in the pathogenesis of at least some of its types . there are sufficient evidences that platelets play a causative role in some situations , while a simple association seems to be the best explanation for the others . however , discrimination between a cause - and - effect role and a mere association is difficult for most cases . thrombotic pulmonary vascular lesions , vasoconstriction and remodeling are the basic mechanisms of pulmonary vascular pathology in ph . platelet functional abnormalities , endothelial disintegrity or dysfunction , and impaired fibrinolysis/ antithrombosis were found in idiopathic ph . it is not clear whether these abnormalities are primary and contributory to ph development , or secondary to this disease . then , those types of ph in which platelets seem to have a greater association are reviewed . medline was searched to find english papers published from january 2006 to june 2010 and review articles from january 2000 to the same date , using the combination of words platelet and pulmonary hypertension . whenever the materials found via this basic research were unsatisfactory in providing information about a subitem of this review , older references were added through a more specific search . in addition , many other references were included based on the experts opinions and citations found in the reviewed papers . pulmonary intravascular thrombosis and thrombotic arteriopathy are common pathological findings in ph [ 1 , 3 ] . increased thromboxane ( txa2 ) and serotonin and decreased prostacyclin ( pgi2 ) and nitric oxide ( no ) enhance platelet aggregation in ph patients . maeda et al found a subpopulation of ph patients with increased propensity to thrombosis as suggested by increased platelet protease - activated receptor 1 ( par1 , a key element in the activation of human platelets by thrombin ) expression and par - mediated surface exposure of p - selectin ( an adhesion molecule , a marker for in vivo platelet activation , and an essential component in thrombus formation ) , associated with thrombocytopenia . it is not clear whether thrombocytopenia in ph patients is an incidental finding , caused by platelet consumption in pulmonary vasculature , or resulted from platelet shearing due to pulmonary microangiopathy as suggested by herve et al . interactions with endothelial cells : endothelial cells ( ec ) participate actively in the process of coagulation . they activate factor x , facilitate the formation of the thrombin - activating prothrombinase complex , activate the extrinsic pathway of coagulation by releasing tissue factor , and produce and release von willebrand factor ( vwf ) . on the other hand ec express thrombomodulin , a high affinity receptor for thrombin , on their surface which prevents cleavage of fibrinogen to fibrin . ec are a source of both tissue plasminogen activator ( t - pa ) , an important activator of plasminogen in the fibrinolytic cascade and plasminogen activator inhibitor-1 ( pai-1 ) , an inhibitor of t - pa . these facts show the importance of ec in regulating the fine balance of prothrombotic and antithrombotic processes . there are evidences in favor of an imbalance in ph patients . in 19 out of 27 patients with idiopathic pah , low soluble thrombomodulin , low fibrinolytic activity , and high fibrinolytic inhibitor levels were seen in idiopathic ph patients . those with secondary ph had elevated fibrinogen levels , increased vwf , and a trend to increased t - pa . it is noteworthy that an additional role for pai- 1 in vascular remodeling was suggested . the studies about such a role for pai-1 in ph are limited in number and conflicting . eicosanoids : activated platelets are the major producers of txa2 , a vasoconstrictive and proaggregatory eicosanoid . it is a physiological antagonist of txa2 , inhibiting platelet aggregation and relaxing vascular smooth muscle . abnormal production of eicosanoids has been demonstrated in idiopathic and secondary ph , including patients with congenital heart diseases before and after surgical correction of these diseases [ 1419 ] . in children with left - to - right shunts and in adolescents with eisenmenger syndrome , the ratio of txa2 to pgi2 metabolites urinary excretion is elevated as compared to control subjects [ 14 , 15 , 19 ] . prostacyclin analogues are important drugs in the treatment of ph , emphasizing the causative role of this eicosanoid in the development of ph . in contrary , it is not known whether txa2 changes are secondary or primary to ph . serotonin : serotonin ( 5-hydroxytriptamine , 5ht ) is produced in the central nervous system ( cns ) , enterochromaffin cells and limitedly in platelets . although platelets are not a large producer of serotonin , they are a major storage site for this mediator outside the cns . platelets readily take up serotonin from plasma , leaving very little circulating . under certain circumstances , first , it is a pulmonary vasoconstrictor , mainly through its 5ht1b receptor . in mice and human , overexpression of 5-ht2b ( another serotonin receptor subtype ) in the pulmonary arterial tree is associated with the development of ph . second , serotonin has mitogenic activity on pulmonary arterial smooth muscle cells ( pasmc ) , causing their hypertrophy and proliferation [ 20 , 23 , 24 ] . it was speculated that highly selective serotonin transporter ( sert ) plays an important role in this mechanism . patients with ph have pasmc with faster growth rate than normal subjects after stimulation by serotonin or serum . selective serotonin transporter inhibitors fluoxetine and citalopram , but not serotonin receptor antagonists ketanserin ( a 5ht2a antagonist ) and gr127935 ( a selective 5ht1b/1d antagonist ) can inhibit those effects [ 19 , 25 ] . sert gene polymorphism was also found to be a determinant of ph severity [ 19 , 26 ] . in addition , a 5hta2-mediated p38 mitogen - activated protein kinase activation with mitogenic effects on pulmonary artery fibroblasts from chronically hypoxic rats was observed [ 19 , 27 ] . last , serotonin stimulates platelet aggregation especially in combination with adenosine diphosphate and txa2 [ 20 , 28 ] . the significance of increased plasma levels of serotonin in ph is not clear . while some studies reported high plasma levels of serotonin in ph patients [ 5 , 29 , 30 ] , some found normal values in their cohort [ 30 , 31 ] . increased serotonin level may be secondary to its impaired metabolism , as pulmonary ec contribute greatly to its clearance and their damage successful therapy by a potent antiaggregatory agent , epoprostenol , and heart - lung transplantation did not lower plasma serotonin levels [ 5 , 29 ] . breuer et al found higher urinary excretion of 5-hydroxyindolacetic acid ( a major metabolite of serotonin ) in ph patients with left to right shunts and contributed it to higher metabolism of serotonin in these patients . vwf is present in the endothelial basement membrane and in plasma . in endothelial basement membrane , vwf acts as a carrier for coagulation factor viii , and within platelet -granules as an adhesive protein . ec stimulation in pathological conditions , like ph is followed by a rapid release of vwf from storage granules into the circulation . plasma level of vwf is used as a marker for ec damage , and increased levels of vwf have been reported in patients with ph [ 33 , 34 ] . plasma antigenic activity of vwf ( vwf : ag ) can be a useful biochemical index for predicting a short - term prognosis in ph . a plasma vwf : ag higher than 240% of standard activity was 54% sensitive and 93% specific for identifying patients who were unlikely to survive one year , with an overall predictive value of 75% . elevated baseline and follow up vwf levels were showed to be associated with worse survival . nitric oxide : endothelium - derived no ( eno ) is a potent inhibitor of platelet aggregation in addition to its vasodilatory and antiproliferative effects . deficiency in endothelial no synthase ( enos ) sensitize mice to hypoxia - induced ph , whereas pulmonary gene transfer of enos could protect the lungs . tetrahydrobiopterin ( bh4 ) is an essential cofactor for the enzymatic activity of all three isoenzymes of nos , including enos . khoo et al showed that mice deficient in bh4 developed ph which can be reversed by increasing bh4 availability . they also found that augmented bh4 production can be protective against hypoxia - induced ph in mice . platelet activating factor : platelet activating factor ( paf ) is a phospholipid with diverse physiological and pathological actions . caplan et al reported high paf plasma levels in newborns with persistent pulmonary hypertension of the newborn ( pphn ) , correlation between plasma paf level and disease severity , and a fall in paf levels as they improved clinically . paf has also been implicated in chronic hypoxia - induced ph in adult rats [ 4042 ] . bixby et al found increased paf synthesis in pulmonary arteries , increased paf receptor protein expression , increased paf receptor binding , and an increase in paf induced smooth muscle cell proliferation in fetal lambs exposed to chronic high altitude hypoxia . it is cleaved from plasminogen at the platelet plasma membrane , absorbed by platelet membrane , and released only upon aggregation [ 4346 ] . overexpression of angiostatin is associated with ph in mice [ 44 , 47 ] . only upon thrombus formation in the pulmonary capillaries would excessive amounts of angiostatin be released in a localized manner , where it could contribute to the ec microfragment formation , injury and/or death , and possibly to the progression of ph . idiopathic pah patients have significantly elevated platelet , but not plasma , angiostatin levels compared to controls . vascular endothelial growth factor : vascular endothelial growth factor ( vegf ) is a growth factor involved in vasculogenesis and angiogenesis . this factor antagonizes the formation of apoptotic endothelial microfragments by angiostatin [ 44 , 48 , 49 ] . a possible role for vegf in the development of ph vegf produced endogenously by ec is also crucial for the maintenance of vascular endothelium [ 50 , 51 ] . cd40 and its ligand : cd40 ligand ( cd40l ) is a transmembrane protein found on the surface of cd4 + t cells and activated platelets as well as in plasma ( soluble form ) . cd40 can be found on the b cells , macrophages , vascular smooth muscle and ec . damas et al showed several evidences in favor of a role for this pathway in ph , including higher levels of soluble cd40l in secondary and idiopathic ph but not in cteph patients , lower levels in patients receiving warfarin , higher levels in arterial blood than in mixed venous samples ( enhanced release or reduced clearance in pulmonary vasculature ) , and increased secretion of soluble cd40l by pallets of ph patients . platelet - derived growth factor : platelet - derived growth factor ( pdgf ) is a disulphide - linked polypeptide comprised of two chains ( a and b ) and appearing as three dimeric isoforms termed pdgf aa , ab , and bb [ 53 , 54 ] . many cell types including smooth muscle cells , and macrophages secrete pdgf - like molecules [ 53 , 54 ] . existence of pdgf - ab in platelets may be confined to humans [ 54 , 55 ] . pdgf - b is processed in platelets into a soluble and active isoform lacking the retention motif . growth factors such as pdgf may participate in the initiation and/or progression of idiopathic pah . there is an evidence that serotonin transactivates pdgf receptor ( pdgfr ) through sert in pasmc . light : lymphotoxin - like inducible protein that competes with glycoprotein d for herpesvirus entry mediator on t lymphocytes ( light ) , is a platelet - derived member of the tissue necrosis factor superfamily . serum levels of light are increased in ph patients and its arterial level correlates with mortality . immunostaining of light and its receptors was observed in alveolar macrophages , vascular smooth muscle cells , and ec in lungs from patients with pah . based on these observations , it was suggested that light may have a role in the pathogenesis of ph , although further studies were recommended as well . platelets and angiogenesis : platelets seem to play a significant role in angiogenesis through their proangiogenic and antiangiogenic factors . platelets and megakaryocytes promote angiogenesis through proangiogenic factors like vegf - a , fibroblast growth factor 2 , epidermal growth factor , pdgf and matrix metallopeptidase 9 [ 4861 ] . on the other hand , they inhibit angiogenesis by their antiangiogenic factors like platelet factor 4 , thrombospondin 1 , 2-macroglobulin , pai-1 , and angiostatin . a disordered or misguided angiogenesis was suggested to be present in patients with severe ph . inflammatory and connective tissue diseases : inflammation appears to play a significant role in some types of pah , including those secondary to connective tissue diseases . pah occurs in patients with systemic sclerosis ( ss ) and crest syndrome ( calcinosis , the raynaud phenomenon , esophageal dysfunction , sclerodactyly , and telangiectasia ) , and less frequently in patients with systemic lupus erythematosus ( sle ) , rheumatoid arthritis , takayasu arteritis , polymyositis , and dermatomyositis . it was hypothesized that the initial lesions appears due to vasoconstriction or vasospasm , but inflammation and excessive platelet adhesion lead to the vasculopathy . activation of the pdgf / pdfgr signaling pathway has been linked to some proliferative and fibrotic disorders including pah and ss . it was suggested that these antibodies may contribute to the development of pah in this disease . pah is also found in 0.5 - 14% of patients with sle , being the third cause of death after infections and organ failure . some of these patients have experienced significant improvements with immunosuppressive therapy , emphasizing the importance of inflammation in this setting . antiphospholipid ( apl ) antibodies have been detected in pah due to thromboembolism and in the primary plexogenic pah . pah may be the only manifestation of the antiphospholipid syndrome ( aps ) , and patients have been observed with very high levels of apl antibodies . the prevalence of pah in primary aps and secondary aps patients is around 3.5% and 1.8% , respectively . apl antibodies found in a greater percentage of sle patients with pah than in those with normal pap . interaction between apl and ec and the resultant vascular remodeling was suggested as the basis of pah development . human immunodeficiency virus(hiv ) infection : several cases of hiv-1 infected patients with idiopathic pah have been reported , raising the question of a causal relationship between these two conditions [ 57 , 7579 ] . the lack of evidence for a direct hiv-1 pulmonary artery infection by means of electron microscopy , immunochemistry , deoxyribonucleic acid in situ hybridization , and polymerase chain reaction in two patients displaying hiv-1-associated idiopathic pah has suggested that hiv-1 may act in these cases through mediator release associated with retroviral infection rather than by direct endothelial infection [ 57 , 76 ] . hemoglobinopathies : pah is one of the complications of sickle cell disease ( scd ) . mild pah ( pap < 35mmhg ) is seen in 20% and moderate to severe degrees ( pap > 45mmhg ) in 10% of the patients . direct inhibition of no by plasma hemoglobin released from damaged red blood cells leads to platelet activation because no is a potent inhibitor of this pathway [ 8082 ] . clinical studies of patients with scd reveal correlations between the intrinsic rate of intravascular hemolysis and blood levels of procoagulant factors [ 80 , 83 , 84 ] . cell - free plasma hemoglobin mediated resistance to no and the development of pah has also been shown in transgenic mouse models of scd and spherocytosis , and in mouse models of alloimmune hemolysis and malaria [ 80 , 85 , 86 ] . no bioavailability is decreased not only through no scavenging by plasma hemoglobin and superoxide , but also through arginine depletion by plasma arginase , and increased no inactivation by reactive oxygen species derived from xanthine oxidase , nicotinamide adenine dinucleotide phosphate - oxidase , hemoglobin s autooxidation , and uncoupled endothelial nitric oxide synthase ( enos ) . in scd patients , plasma level of pdgf bb correlated positively with tricuspid valve regurgitation velocity ( which reflects systolic pap ) , while that of vegf negatively correlated . activated platelets might be a source of increased plasma pdgf levels in scd [ 82 , 88 ] . ph is found in 1075% of patients with thalassemia and can be the leading cause of heart failure in these patients [ 8992 ] . prior splenectomy , older age , and evidence for chronic hemolysis were significantly associated with pah . this can trigger low - grade hypercoagulability , which is enhanced in splenectomized patients [ 9294 ] . alternatively , there is a growing evidence that hemolysis - induced no scavenging is responsible for the pah development in thalassemia , causing platelet activation , thrombosis , and endothelial dysfunction [ 92 , 95 ] . singer et al found higher soluble p - selectin levels in pulmonary hypertensive thalassemic patients in comparison with pulmonary normotensive ones . they also found lower protein c in these patients which may contribute to a hypercoagulable state , but its role in the development of pah is unknown . it was reported that a shorter platelets life span in both splenectomized and non - splenectomiszed patients with thalassemia than in non - thalassemic splenectomized patients [ 96 , 97 ] . thromboembolic ph : acute massive pulmonary thromboembolism ( pte ) increases pap and pvr . in some subjects including a small number ( 0.1- 3.8% ) of pte patients , a chronic state of thromboembolism leads to ph [ 98 , 99 ] . the pathophysiology of cteph is not completely understood : proposed mechanisms include a t - pa / pai-1 imbalance , and lysis - resistant fibrinogen variants [ 101 , 102 ] . a difficult situation is to distinguish an acute ph in an already normal pte patient from an acute embolism in an unrecognized cteph patient as these two conditions need different treatment algorithms . lifelong anticoagulation is required for all cteph patients , while antiplatelet therapy is indicated in some . ph crisis after cardiopulmonary bypass : after cardiac surgery , a sudden increase in pap and pvr may occur .. the pathophysiology of these problematic and sometimes fatal episodes , called pulmonary hypertensive crisis , is complex and not well understood yet . the exposure of platelets to the artificial membrane during cardiopulmonary bypass may activate them and contribute to this process . endothelial injury , hypothermia , and nonpulsatile perfusion may be more important factors than the artificial membrane in this situation . the mechanism of endothelial injury is not well understood ; however , ischemia - reperfusion injury could be its main basis . endothelial injury impairs the balance between vasodilatory and vasoconstrictive mechanisms in favor of the latter , and promotes platelet aggregation and activation . drug- and toxin - induced pah : pah may develop after using anorexigen drugs such as fenfluramines , aminorex and toxins like rapeseed oil . although there is an accepted belief that these drugs potentiate pah through their serotonin releasing properties [ 22 , 105 ] , there are controversies as dexfenfluramine can actually lower blood serotonin and may only slightly elevate plasma serotonin to nontoxic levels [ 105107 ] . often the fenfluramines and phentermine were co - administered . the combination of fenfluramine / phentermine is known to increase sert activity [ 20 , 108 ] . essential thrombocythemia ( et ) : altintas et al found ph in 47.8% of et patients . there was a statistically significant difference in platelet counts between et patients with ph and without ph . anticoagulation : abnormalities of the activated clotting system [ 32 , 110112 ] , impaired fibrino - lysis [ 11 , 112 , 113 ] , abnormal platelet function [ 16 , 112 , 114 ] , histological evidence of microvascular thrombosis [ 112 , 115 , 116 ] , ec dysfunction and injury , and increased tendency to develop deep vein thrombosis due to low cardiac output and sedentary life in chronic patients are the rationale to use anticoagulants in ph [ 9 , 112 ] . however , there is no randomized controlled trial and only observational studies data supports their administration [ 9 , 112 , 117 ] . in a systematic review , johnson et al reported that five observational studies suggested a survival benefit associated with warfarin in the treatment of idiopathic ph , whereas two others did not support this association . anticoagulants are indicated for idiopathic ph ( class iia , level of evidence c ) and permitted for secondary ph ( class iib , level of evidence c ) [ 117 , 118 ] . prostacyclin and its analogues : several reports have shown that prostacyclin therapy directly inhibits platelets [ 9 , 119121 ] . it is not clear whether epoprostenol , ph , or both cause this complication , although the drug seems to play a greater role . in one patient in whom epoprostenol was discontinued , platelet counts improved after discontinuation of epoprostenol despite worsening hemodynamics , and then fell after re - initiation at a lower dose despite improvement in hemodynamics , suggesting that epoprostenol caused the thrombocytopenia . the mechanism of epoprostenol - induced thrombocytopenia is unknown , as well as its significance . in addition , prostacyclin therapy in ph was associated with a significant decrease in serum levels of light . a recent study confirmed platelet inhibitory function of epoprostenol by preventing platelet aggregation and platelet - leukocyte conjugates formation . the observed results on platelet function were postulated to explain , at least partly , the beneficial effects of this drug in ph patients . phosphodiesterase type 5 inhibitors : no is an important molecule in a number of cellular functions , including the regulation of vascular smooth muscle tone [ 125 , 126 ] . the physiological target of no is soluble guanylate cyclase , the enzyme which catalyses the conversion of guanosine triphosphate ( gtp ) to the intracellular second messenger cyclic guanosine monophosphate ( cgmp ) , mediating no induced relaxation [ 126 , 127 ] . intracellular cgmp is rapidly inactivated to guanosine monophosphate ( gmp ) by the action of cyclic nucleotide phosphodiesterases ( pdes ) . therefore , cgmp concentration in smooth muscle cells is mainly dependent on the balance between the synthesis by soluble guanylate cyclase and the breakdown by pdes , which represents the unique degradation pathway for this second messenger [ 126 , 128 , 129 ] . there exist 11 distinct pde isoenzymes which differ in their substrates , stimulators , inhibitors or gene homology [ 126 , 130 ] . pde5 is the isoenzyme highly presented in pulmonary vasculature [ 126 , 131 , 132 ] , and pulmonary vasodilatation has been resulted from its inhibition [ 126 , 133135 ] . these inhibitors , specifically sildenafil , received attention for their action on the pulmonary vasculature and the observed beneficial effects in the treatment of ph [ 126 , 136139 ] . as pde5 is present in human platelets , the effect of no and no donors on platelet function is potentiated by sildenafil [ 82 , 140 , 141 ] . enhancement of platelet sensitivity to no by pde5 inhibition returns platelet activation to more normal levels in patients with scd and pah . this effect is added to the beneficial effects of sildenafil on endothelial function in these patients . this drug significantly reduced the ca mobilization and ca influx in thrombin - stimulated rabbit washed platelets . nitric oxide : inhaled no is administered for the acute treatment of ph , mostly after cardiac surgery and in pphn . as mentioned previously , this drug is a potent inhibitor of platelet activation . beghetti et al found that 30 ppm inhaled no inhibits platelet aggregation after stimulation by collagen , arachidonic acid , and epinephrine . it was postulated that platelet effects of no should be mediated through a cgmp - independent mechanism , in contrary to the vascular effects . et-1 is overexpressed in ph and may be an important factor in the initiation or progression of the disease . the et-1 effects can be mediated directly through its receptors on the platelets , or indirectly through activation of prostaglandin synthesis [ 144 , 145 ] . iannone et al showed that serum levels of the soluble form of platelet ec adhesion molecule-1 ( pecam-1 ) is increased in patients with systemic sclerosis and pah , and bosentan therapy can return it to the normal values . phosphodiesterase type 3 inhibitors : pulmo - nary vasodilation can be induced by milrinone through its action on a cyclic adenylate monophosphate pathway . clinically , it is used for the treatment of pphn and postoperative ph [ 149 , 150 ] . it is not known whether the vasodilatory role of mirinone is solely responsible for its pulmonary antihypertensive action , or its antiplatelet role may be important as well . kikura et al found no difference in platelet count , bleeding time , and platelet aggregation between cardiac postoperative patients receiving milrinone or not . tanaka et al speculated that at least part of the pulmonary antihypertensive action of milrinone may be through its platelet inhibitory properties . pdgfr inhibitors : the multi - kinase inhibitor ( including pdgfr ) imatinib mesylate reversed pulmonary vascular remodeling in rats with monocrotaline - induced pah and in chronically hypoxic mice [ 154 , 155 ] . addition of imatinib to approved ph drugs was reported to improve pulmonary hemodynamics and functional capacity of some patients with severe pah [ 156159 ] . a completed phase ii clinical trial investigating the safety and efficacy of imatinib mesylate in ph failed to meet the primary efficacy end point of improvement in exercise capacity . the combined inhibition of tyrosine and serine / threonine kinases can provide an option to treat ph and associated right heart remodeling . serotonin antagonists : although there is general agreement that serotonin is important in the pathophysiology of pah , no serotonin antagonist exists with clinically accepted effects in this disease . several agents are targets for investigation in human pah , including the highly selective 5-ht2b antagonist prx-08066 and escitalopram ( a serotonin reuptake inhibitor ) . there is a bulk of evidence in favor of a complex association between platelets and ph . although there is a small number of reports against a causative role and a risk that many of these observations be secondary to ph , it seems that the role of these blood elements can not be overlooked in the pathophysiology of ph . the author tried to provide a comprehensive collection of evidences ; however , the presented list of associations between platelets and ph may be incomplete as these relations are numerous , complex , and many of them not well understood . in addition , ph is a heterogeneous disease with diverse pathophysiological bases , and the relation of platelets to each type may be different . in spite of these evidences , the specific antiplatelet drugs such as aspirin and clopidogrel were not studied sufficiently in ph patients . in addition , no randomized clinical trial studied the role of anticoagulants in ph . these can make the basis of future researches on the relation of platelets and ph . pulmonary intravascular thrombosis and thrombotic arteriopathy are common pathological findings in ph [ 1 , 3 ] . increased thromboxane ( txa2 ) and serotonin and decreased prostacyclin ( pgi2 ) and nitric oxide ( no ) enhance platelet aggregation in ph patients . maeda et al found a subpopulation of ph patients with increased propensity to thrombosis as suggested by increased platelet protease - activated receptor 1 ( par1 , a key element in the activation of human platelets by thrombin ) expression and par - mediated surface exposure of p - selectin ( an adhesion molecule , a marker for in vivo platelet activation , and an essential component in thrombus formation ) , associated with thrombocytopenia . it is not clear whether thrombocytopenia in ph patients is an incidental finding , caused by platelet consumption in pulmonary vasculature , or resulted from platelet shearing due to pulmonary microangiopathy as suggested by herve et al . interactions with endothelial cells : endothelial cells ( ec ) participate actively in the process of coagulation . they activate factor x , facilitate the formation of the thrombin - activating prothrombinase complex , activate the extrinsic pathway of coagulation by releasing tissue factor , and produce and release von willebrand factor ( vwf ) . on the other hand ec express thrombomodulin , a high affinity receptor for thrombin , on their surface which prevents cleavage of fibrinogen to fibrin . ec are a source of both tissue plasminogen activator ( t - pa ) , an important activator of plasminogen in the fibrinolytic cascade and plasminogen activator inhibitor-1 ( pai-1 ) , an inhibitor of t - pa . these facts show the importance of ec in regulating the fine balance of prothrombotic and antithrombotic processes . there are evidences in favor of an imbalance in ph patients . in 19 out of 27 patients with idiopathic pah , low soluble thrombomodulin , low fibrinolytic activity , and high fibrinolytic inhibitor levels were seen in idiopathic ph patients . those with secondary ph had elevated fibrinogen levels , increased vwf , and a trend to increased t - pa . it is noteworthy that an additional role for pai- 1 in vascular remodeling was suggested . the studies about such a role for pai-1 in ph are limited in number and conflicting . eicosanoids : activated platelets are the major producers of txa2 , a vasoconstrictive and proaggregatory eicosanoid . it is a physiological antagonist of txa2 , inhibiting platelet aggregation and relaxing vascular smooth muscle . abnormal production of eicosanoids has been demonstrated in idiopathic and secondary ph , including patients with congenital heart diseases before and after surgical correction of these diseases [ 1419 ] . in children with left - to - right shunts and in adolescents with eisenmenger syndrome , the ratio of txa2 to pgi2 metabolites urinary excretion is elevated as compared to control subjects [ 14 , 15 , 19 ] . prostacyclin analogues are important drugs in the treatment of ph , emphasizing the causative role of this eicosanoid in the development of ph . in contrary , it is not known whether txa2 changes are secondary or primary to ph . serotonin : serotonin ( 5-hydroxytriptamine , 5ht ) is produced in the central nervous system ( cns ) , enterochromaffin cells and limitedly in platelets . although platelets are not a large producer of serotonin , they are a major storage site for this mediator outside the cns . platelets readily take up serotonin from plasma , leaving very little circulating . under certain circumstances , first , it is a pulmonary vasoconstrictor , mainly through its 5ht1b receptor . in mice and human , overexpression of 5-ht2b ( another serotonin receptor subtype ) in the pulmonary arterial tree is associated with the development of ph . second , serotonin has mitogenic activity on pulmonary arterial smooth muscle cells ( pasmc ) , causing their hypertrophy and proliferation [ 20 , 23 , 24 ] . it was speculated that highly selective serotonin transporter ( sert ) plays an important role in this mechanism . patients with ph have pasmc with faster growth rate than normal subjects after stimulation by serotonin or serum . selective serotonin transporter inhibitors fluoxetine and citalopram , but not serotonin receptor antagonists ketanserin ( a 5ht2a antagonist ) and gr127935 ( a selective 5ht1b/1d antagonist ) can inhibit those effects [ 19 , 25 ] . sert gene polymorphism was also found to be a determinant of ph severity [ 19 , 26 ] . in addition , a 5hta2-mediated p38 mitogen - activated protein kinase activation with mitogenic effects on pulmonary artery fibroblasts from chronically hypoxic rats was observed [ 19 , 27 ] . last , serotonin stimulates platelet aggregation especially in combination with adenosine diphosphate and txa2 [ 20 , 28 ] . the significance of increased plasma levels of serotonin in ph is not clear . while some studies reported high plasma levels of serotonin in ph patients [ 5 , 29 , 30 ] , some found normal values in their cohort [ 30 , 31 ] . increased serotonin level may be secondary to its impaired metabolism , as pulmonary ec contribute greatly to its clearance and their damage can be a sign of idiopathic ph . successful therapy by a potent antiaggregatory agent , epoprostenol , and heart - lung transplantation did not lower plasma serotonin levels [ 5 , 29 ] . breuer et al found higher urinary excretion of 5-hydroxyindolacetic acid ( a major metabolite of serotonin ) in ph patients with left to right shunts and contributed it to higher metabolism of serotonin in these patients . vwf is present in the endothelial basement membrane and in plasma . in endothelial basement membrane , vwf acts as a carrier for coagulation factor viii , and within platelet -granules as an adhesive protein . ec stimulation in pathological conditions , like ph is followed by a rapid release of vwf from storage granules into the circulation . plasma level of vwf is used as a marker for ec damage , and increased levels of vwf have been reported in patients with ph [ 33 , 34 ] . plasma antigenic activity of vwf ( vwf : ag ) can be a useful biochemical index for predicting a short - term prognosis in ph . a plasma vwf : ag higher than 240% of standard activity was 54% sensitive and 93% specific for identifying patients who were unlikely to survive one year , with an overall predictive value of 75% . elevated baseline and follow up vwf levels were showed to be associated with worse survival . nitric oxide : endothelium - derived no ( eno ) is a potent inhibitor of platelet aggregation in addition to its vasodilatory and antiproliferative effects . deficiency in endothelial no synthase ( enos ) sensitize mice to hypoxia - induced ph , whereas pulmonary gene transfer of enos could protect the lungs . tetrahydrobiopterin ( bh4 ) is an essential cofactor for the enzymatic activity of all three isoenzymes of nos , including enos . khoo et al showed that mice deficient in bh4 developed ph which can be reversed by increasing bh4 availability . they also found that augmented bh4 production can be protective against hypoxia - induced ph in mice . platelet activating factor : platelet activating factor ( paf ) is a phospholipid with diverse physiological and pathological actions . caplan et al reported high paf plasma levels in newborns with persistent pulmonary hypertension of the newborn ( pphn ) , correlation between plasma paf level and disease severity , and a fall in paf levels as they improved clinically . paf has also been implicated in chronic hypoxia - induced ph in adult rats [ 4042 ] . bixby et al found increased paf synthesis in pulmonary arteries , increased paf receptor protein expression , increased paf receptor binding , and an increase in paf induced smooth muscle cell proliferation in fetal lambs exposed to chronic high altitude hypoxia . it is cleaved from plasminogen at the platelet plasma membrane , absorbed by platelet membrane , and released only upon aggregation [ 4346 ] . overexpression of angiostatin is associated with ph in mice [ 44 , 47 ] . only upon thrombus formation in the pulmonary capillaries would excessive amounts of angiostatin be released in a localized manner , where it could contribute to the ec microfragment formation , injury and/or death , and possibly to the progression of ph . idiopathic pah patients have significantly elevated platelet , but not plasma , angiostatin levels compared to controls . vascular endothelial growth factor : vascular endothelial growth factor ( vegf ) is a growth factor involved in vasculogenesis and angiogenesis . this factor antagonizes the formation of apoptotic endothelial microfragments by angiostatin [ 44 , 48 , 49 ] . a possible role for vegf in the development of ph is suggested but not approved yet . vegf produced endogenously by ec is also crucial for the maintenance of vascular endothelium [ 50 , 51 ] . cd40 and its ligand : cd40 ligand ( cd40l ) is a transmembrane protein found on the surface of cd4 + t cells and activated platelets as well as in plasma ( soluble form ) . cd40 can be found on the b cells , macrophages , vascular smooth muscle and ec . damas et al showed several evidences in favor of a role for this pathway in ph , including higher levels of soluble cd40l in secondary and idiopathic ph but not in cteph patients , lower levels in patients receiving warfarin , higher levels in arterial blood than in mixed venous samples ( enhanced release or reduced clearance in pulmonary vasculature ) , and increased secretion of soluble cd40l by pallets of ph patients . platelet - derived growth factor : platelet - derived growth factor ( pdgf ) is a disulphide - linked polypeptide comprised of two chains ( a and b ) and appearing as three dimeric isoforms termed pdgf aa , ab , and bb [ 53 , 54 ] . many cell types including smooth muscle cells , and macrophages secrete pdgf - like molecules [ 53 , 54 ] . existence of pdgf - ab in platelets may be confined to humans [ 54 , 55 ] . pdgf - b is processed in platelets into a soluble and active isoform lacking the retention motif . growth factors such as pdgf may participate in the initiation and/or progression of idiopathic pah . there is an evidence that serotonin transactivates pdgf receptor ( pdgfr ) through sert in pasmc . light : lymphotoxin - like inducible protein that competes with glycoprotein d for herpesvirus entry mediator on t lymphocytes ( light ) , is a platelet - derived member of the tissue necrosis factor superfamily . serum levels of light are increased in ph patients and its arterial level correlates with mortality . immunostaining of light and its receptors was observed in alveolar macrophages , vascular smooth muscle cells , and ec in lungs from patients with pah . based on these observations , it was suggested that light may have a role in the pathogenesis of ph , although further studies were recommended as well . platelets and angiogenesis : platelets seem to play a significant role in angiogenesis through their proangiogenic and antiangiogenic factors . platelets and megakaryocytes promote angiogenesis through proangiogenic factors like vegf - a , fibroblast growth factor 2 , epidermal growth factor , pdgf and matrix metallopeptidase 9 [ 4861 ] . on the other hand , they inhibit angiogenesis by their antiangiogenic factors like platelet factor 4 , thrombospondin 1 , 2-macroglobulin , pai-1 , and angiostatin . a disordered or misguided angiogenesis was suggested to be present in patients with severe ph . inflammatory and connective tissue diseases : inflammation appears to play a significant role in some types of pah , including those secondary to connective tissue diseases . pah occurs in patients with systemic sclerosis ( ss ) and crest syndrome ( calcinosis , the raynaud phenomenon , esophageal dysfunction , sclerodactyly , and telangiectasia ) , and less frequently in patients with systemic lupus erythematosus ( sle ) , rheumatoid arthritis , takayasu arteritis , polymyositis , and dermatomyositis . it was hypothesized that the initial lesions appears due to vasoconstriction or vasospasm , but inflammation and excessive platelet adhesion lead to the vasculopathy . activation of the pdgf / pdfgr signaling pathway has been linked to some proliferative and fibrotic disorders including pah and ss . it was suggested that these antibodies may contribute to the development of pah in this disease . pah is also found in 0.5 - 14% of patients with sle , being the third cause of death after infections and organ failure . some of these patients have experienced significant improvements with immunosuppressive therapy , emphasizing the importance of inflammation in this setting . antiphospholipid ( apl ) antibodies have been detected in pah due to thromboembolism and in the primary plexogenic pah . pah may be the only manifestation of the antiphospholipid syndrome ( aps ) , and patients have been observed with very high levels of apl antibodies . the prevalence of pah in primary aps and secondary aps patients is around 3.5% and 1.8% , respectively . apl antibodies found in a greater percentage of sle patients with pah than in those with normal pap . interaction between apl and ec and the resultant vascular remodeling was suggested as the basis of pah development . human immunodeficiency virus(hiv ) infection : several cases of hiv-1 infected patients with idiopathic pah have been reported , raising the question of a causal relationship between these two conditions [ 57 , 7579 ] . the lack of evidence for a direct hiv-1 pulmonary artery infection by means of electron microscopy , immunochemistry , deoxyribonucleic acid in situ hybridization , and polymerase chain reaction in two patients displaying hiv-1-associated idiopathic pah has suggested that hiv-1 may act in these cases through mediator release associated with retroviral infection rather than by direct endothelial infection [ 57 , 76 ] . hemoglobinopathies : pah is one of the complications of sickle cell disease ( scd ) . mild pah ( pap < 35mmhg ) is seen in 20% and moderate to severe degrees ( pap > 45mmhg ) in 10% of the patients . direct inhibition of no by plasma hemoglobin released from damaged red blood cells leads to platelet activation because no is a potent inhibitor of this pathway [ 8082 ] . clinical studies of patients with scd reveal correlations between the intrinsic rate of intravascular hemolysis and blood levels of procoagulant factors [ 80 , 83 , 84 ] . cell - free plasma hemoglobin mediated resistance to no and the development of pah has also been shown in transgenic mouse models of scd and spherocytosis , and in mouse models of alloimmune hemolysis and malaria [ 80 , 85 , 86 ] . no bioavailability is decreased not only through no scavenging by plasma hemoglobin and superoxide , but also through arginine depletion by plasma arginase , and increased no inactivation by reactive oxygen species derived from xanthine oxidase , nicotinamide adenine dinucleotide phosphate - oxidase , hemoglobin s autooxidation , and uncoupled endothelial nitric oxide synthase ( enos ) . in scd patients , plasma level of pdgf bb correlated positively with tricuspid valve regurgitation velocity ( which reflects systolic pap ) , while that of vegf negatively correlated . activated platelets might be a source of increased plasma pdgf levels in scd [ 82 , 88 ] . ph is found in 1075% of patients with thalassemia and can be the leading cause of heart failure in these patients [ 8992 ] . prior splenectomy , older age , and evidence for chronic hemolysis were significantly associated with pah . this can trigger low - grade hypercoagulability , which is enhanced in splenectomized patients [ 9294 ] . alternatively , there is a growing evidence that hemolysis - induced no scavenging is responsible for the pah development in thalassemia , causing platelet activation , thrombosis , and endothelial dysfunction [ 92 , 95 ] . singer et al found higher soluble p - selectin levels in pulmonary hypertensive thalassemic patients in comparison with pulmonary normotensive ones . they also found lower protein c in these patients which may contribute to a hypercoagulable state , but its role in the development of pah is unknown . it was reported that a shorter platelets life span in both splenectomized and non - splenectomiszed patients with thalassemia than in non - thalassemic splenectomized patients [ 96 , 97 ] . thromboembolic ph : acute massive pulmonary thromboembolism ( pte ) increases pap and pvr . in some subjects including a small number ( 0.1- 3.8% ) of pte patients , a chronic state of thromboembolism leads to ph [ 98 , 99 ] . the pathophysiology of cteph is not completely understood : proposed mechanisms include a t - pa / pai-1 imbalance , and lysis - resistant fibrinogen variants [ 101 , 102 ] . a difficult situation is to distinguish an acute ph in an already normal pte patient from an acute embolism in an unrecognized cteph patient as these two conditions need different treatment algorithms . lifelong anticoagulation is required for all cteph patients , while antiplatelet therapy is indicated in some . ph crisis after cardiopulmonary bypass : after cardiac surgery , a sudden increase in pap and pvr may occur .. the pathophysiology of these problematic and sometimes fatal episodes , called pulmonary hypertensive crisis , is complex and not well understood yet . the exposure of platelets to the artificial membrane during cardiopulmonary bypass may activate them and contribute to this process . endothelial injury , hypothermia , and nonpulsatile perfusion may be more important factors than the artificial membrane in this situation . the mechanism of endothelial injury is not well understood ; however , ischemia - reperfusion injury could be its main basis . endothelial injury impairs the balance between vasodilatory and vasoconstrictive mechanisms in favor of the latter , and promotes platelet aggregation and activation . drug- and toxin - induced pah : pah may develop after using anorexigen drugs such as fenfluramines , aminorex and toxins like rapeseed oil . although there is an accepted belief that these drugs potentiate pah through their serotonin releasing properties [ 22 , 105 ] , there are controversies as dexfenfluramine can actually lower blood serotonin and may only slightly elevate plasma serotonin to nontoxic levels [ 105107 ] . the combination of fenfluramine / phentermine is known to increase sert activity [ 20 , 108 ] . essential thrombocythemia ( et ) : altintas et al found ph in 47.8% of et patients . there was a statistically significant difference in platelet counts between et patients with ph and without ph . anticoagulation : abnormalities of the activated clotting system [ 32 , 110112 ] , impaired fibrino - lysis [ 11 , 112 , 113 ] , abnormal platelet function [ 16 , 112 , 114 ] , histological evidence of microvascular thrombosis [ 112 , 115 , 116 ] , ec dysfunction and injury , and increased tendency to develop deep vein thrombosis due to low cardiac output and sedentary life in chronic patients are the rationale to use anticoagulants in ph [ 9 , 112 ] . however , there is no randomized controlled trial and only observational studies data supports their administration [ 9 , 112 , 117 ] . in a systematic review , johnson et al reported that five observational studies suggested a survival benefit associated with warfarin in the treatment of idiopathic ph , whereas two others did not support this association . anticoagulants are indicated for idiopathic ph ( class iia , level of evidence c ) and permitted for secondary ph ( class iib , level of evidence c ) [ 117 , 118 ] . prostacyclin and its analogues : several reports have shown that prostacyclin therapy directly inhibits platelets [ 9 , 119121 ] . it is not clear whether epoprostenol , ph , or both cause this complication , although the drug seems to play a greater role . in one patient in whom epoprostenol was discontinued , platelet counts improved after discontinuation of epoprostenol despite worsening hemodynamics , and then fell after re - initiation at a lower dose despite improvement in hemodynamics , suggesting that epoprostenol caused the thrombocytopenia . the mechanism of epoprostenol - induced thrombocytopenia is unknown , as well as its significance . in addition , prostacyclin therapy in ph was associated with a significant decrease in serum levels of light . a recent study confirmed platelet inhibitory function of epoprostenol by preventing platelet aggregation and platelet - leukocyte conjugates formation . the observed results on platelet function were postulated to explain , at least partly , the beneficial effects of this drug in ph patients . phosphodiesterase type 5 inhibitors : no is an important molecule in a number of cellular functions , including the regulation of vascular smooth muscle tone [ 125 , 126 ] . the physiological target of no is soluble guanylate cyclase , the enzyme which catalyses the conversion of guanosine triphosphate ( gtp ) to the intracellular second messenger cyclic guanosine monophosphate ( cgmp ) , mediating no induced relaxation [ 126 , 127 ] . intracellular cgmp is rapidly inactivated to guanosine monophosphate ( gmp ) by the action of cyclic nucleotide phosphodiesterases ( pdes ) . therefore , cgmp concentration in smooth muscle cells is mainly dependent on the balance between the synthesis by soluble guanylate cyclase and the breakdown by pdes , which represents the unique degradation pathway for this second messenger [ 126 , 128 , 129 ] . there exist 11 distinct pde isoenzymes which differ in their substrates , stimulators , inhibitors or gene homology [ 126 , 130 ] . pde5 is the isoenzyme highly presented in pulmonary vasculature [ 126 , 131 , 132 ] , and pulmonary vasodilatation has been resulted from its inhibition [ 126 , 133135 ] . these inhibitors , specifically sildenafil , received attention for their action on the pulmonary vasculature and the observed beneficial effects in the treatment of ph [ 126 , 136139 ] . as pde5 is present in human platelets , the effect of no and no donors on platelet function is potentiated by sildenafil [ 82 , 140 , 141 ] . enhancement of platelet sensitivity to no by pde5 inhibition returns platelet activation to more normal levels in patients with scd and pah . this effect is added to the beneficial effects of sildenafil on endothelial function in these patients . this drug significantly reduced the ca mobilization and ca influx in thrombin - stimulated rabbit washed platelets . this action enhances pulmonary vasodilatory effect of vardenafil . nitric oxide : inhaled no is administered for the acute treatment of ph , mostly after cardiac surgery and in pphn . as mentioned previously , this drug is a potent inhibitor of platelet activation . beghetti et al found that 30 ppm inhaled no inhibits platelet aggregation after stimulation by collagen , arachidonic acid , and epinephrine . it was postulated that platelet effects of no should be mediated through a cgmp - independent mechanism , in contrary to the vascular effects . et-1 is overexpressed in ph and may be an important factor in the initiation or progression of the disease . the et-1 effects can be mediated directly through its receptors on the platelets , or indirectly through activation of prostaglandin synthesis [ 144 , 145 ] . iannone et al showed that serum levels of the soluble form of platelet ec adhesion molecule-1 ( pecam-1 ) is increased in patients with systemic sclerosis and pah , and bosentan therapy can return it to the normal values . phosphodiesterase type 3 inhibitors : pulmo - nary vasodilation can be induced by milrinone through its action on a cyclic adenylate monophosphate pathway . clinically , it is used for the treatment of pphn and postoperative ph [ 149 , 150 ] . it is not known whether the vasodilatory role of mirinone is solely responsible for its pulmonary antihypertensive action , or its antiplatelet role may be important as well . kikura et al found no difference in platelet count , bleeding time , and platelet aggregation between cardiac postoperative patients receiving milrinone or not . tanaka et al speculated that at least part of the pulmonary antihypertensive action of milrinone may be through its platelet inhibitory properties . pdgfr inhibitors : the multi - kinase inhibitor ( including pdgfr ) imatinib mesylate reversed pulmonary vascular remodeling in rats with monocrotaline - induced pah and in chronically hypoxic mice [ 154 , 155 ] . addition of imatinib to approved ph drugs was reported to improve pulmonary hemodynamics and functional capacity of some patients with severe pah [ 156159 ] . a completed phase ii clinical trial investigating the safety and efficacy of imatinib mesylate in ph failed to meet the primary efficacy end point of improvement in exercise capacity . the combined inhibition of tyrosine and serine / threonine kinases can provide an option to treat ph and associated right heart remodeling . serotonin antagonists : although there is general agreement that serotonin is important in the pathophysiology of pah , no serotonin antagonist exists with clinically accepted effects in this disease . several agents are targets for investigation in human pah , including the highly selective 5-ht2b antagonist prx-08066 and escitalopram ( a serotonin reuptake inhibitor ) . there is a bulk of evidence in favor of a complex association between platelets and ph . although there is a small number of reports against a causative role and a risk that many of these observations be secondary to ph , it seems that the role of these blood elements can not be overlooked in the pathophysiology of ph . the author tried to provide a comprehensive collection of evidences ; however , the presented list of associations between platelets and ph may be incomplete as these relations are numerous , complex , and many of them not well understood . in addition , ph is a heterogeneous disease with diverse pathophysiological bases , and the relation of platelets to each type may be different . in spite of these evidences , the specific antiplatelet drugs such as aspirin and clopidogrel were not studied sufficiently in ph patients . these can make the basis of future researches on the relation of platelets and ph . in summary , platelets not only participate actively in thrombus formation , but also produce ( txa2 , light , angiostatin , and pdgf ) , store ( serotonin , vwf , and vegf ) , and release mediators that may contribute to the initiation or aggravation of ph ( fig . platelets are related to all three basic mechanisms of ph : vasoconstriction ( serotonin and txa2 ) , thrombotic lesions ( aggregation , serotonin , txa2 , cd40l , and vwf ) , and remodeling ( serotonin , cd40l , proangiogenic and antiangiogenic factors ) . summary of the major mechanisms of platelets associations with pulmonary vasoconstriction , thrombus formation , and remodeling in the pulmonary vessels . antiang : antiangiogenic facrors ( platelet factor 4 , thrombospondin 1 , 2-macroglobulin , plasminogen activator inhibitor-1 , and angiostatin ) ; cd40l , cd40 ligand ; proang : proangiogenic factors ( vascular endothelial growth factor a , fibroblast growth factor 2 , epidermal growth factor , platelet - derived growth factor and matrix metallopeptidase 9 ) ; txa2 : thromboxane a2 ; vwf : von willebrand factor .

pathophysiology of pulmonary arterial hypertension is based on three basic mechanisms : thrombotic pulmonary vascular lesions , vasoconstriction and vascular remodeling . platelets are related to all of these mechanisms by their aggregation , production , storage and release of several mediators . the role of platelets is more prominent in some types of pulmonary arterial hypertension , including those which are secondary to inflammatory and infectious diseases , hemoglobinopathies , essential thrombocythemia , drugs , thromboembolism , and cardiac surgery . most pulmonary antihypertensive drugs have a negative effect on platelets . in this review , the mechanisms of platelets association with pulmonary arterial hypertension , those types of pulmonary arterial hypertension with greatest platelet contribution to their pathophysiology , and the effects of pulmonary antihypertensive drugs on platelets are summarized .

SECTION 1. SHORT TITLE. This Act may be cited as the ``United States-India Energy Security Cooperation Act of 2006''. SEC. 2. FINDINGS. (1) The December 2004 National Intelligence Council report entitled ``Mapping the Global Future in 2020'' states that the single most important factor affecting the demand for energy will be global economic growth, especially that of China and India. It is estimated that the current economic growth rate in India is approximately 7 percent of gross domestic product. India will need to double its energy consumption within the next 15 years to maintain steady rates of economic growth. (2) The United States and India launched an energy dialogue on May 31, 2005, aimed at building upon a broad range of existing energy cooperation and developing new avenues of collaboration on energy. These efforts will promote increased trade and investment in the energy sector by utilizing resources in the public and private sectors, focusing on oil and gas, power and energy efficiency, new technologies and renewable energy, coal and clean coal technology, and civil nuclear cooperation. In his testimony before the Committee on Foreign Relations of the Senate on July 26, 2005, Under Secretary of Energy David Garman said, ``The United States and India recognize their mutual interests are best served by working together in a collaborative fashion to ensure stability in global energy markets.''. (3) As the sixth largest energy consumer in the world, India satisfies 70 percent of its oil demand with imports and has embarked on an aggressive oil and gas exploration program. The largest discovery of natural gas in the world in 2002 occurred in India. In 2003, the largest discovery of oil in the world occurred in the state of Rajasthan in India. External funding and investment in the oil and gas industry in India is necessary to maximize recovery from oil fields, but an improved investment environment in India is needed to attract such investment. (4) India is the world's third largest producer of coal and will continue to rely on coal as a major energy source to support expanding industrial and electric power generation needs. However, many of India's coal-fired plants are inefficient and lack adequate pollution control equipment. In his address to a joint session of the United States Congress on July 19, 2005, Prime Minister of India Manmohan Singh noted the importance of allowing greater access for developing countries to clean coal technologies and of exploring partnerships that encourage more efficient use of hydrocarbon resources. (5) India provides a market for United States technologies that promote the clean and efficient use of energy. (6) India has announced plans to develop a 5,000,000 ton strategic crude oil reserve, which is expected to be completed by 2009. (7) United States energy experts have emphasized the need for the United States to increase collaboration with other countries-- (A) to develop and deploy energy technologies that will not be pursued absent greater Federal support; (B) to increase investment in cooperative international energy research; and (C) to expand the global network of strategic petroleum reserves. SEC. 3. STATEMENT OF POLICY. It is the policy of the United States-- (1) to cooperate with India to address common energy challenges, to ensure future global energy security, and to increase the world-wide availability of clean energy; (2) to promote dialogue and increased understanding between the United States and India on our respective national energy policies and strategies as an integral part of the expanding strategic partnership between the two countries; and (3) to collaborate with India in energy research that fosters market-based approaches to energy security and offers the promise of technological breakthroughs that reduce oil dependency globally. SEC. 4. ASSISTANCE TO SUPPORT ENERGY COOPERATION. (a) Authorization.--The President is authorized to establish programs in support of greater energy cooperation between the United States and India. (b) Activities.--Assistance may be provided under this section for cooperation related to-- (1) research, development, and deployment of clean coal and emission reduction technologies and carbon sequestration projects; (2) research, development, and deployment of alternative fuel sources, such as ethanol, bio-mass, and coal-based fuels; (3) research, development, and deployment of energy efficiency projects; (4) research related to commercially available technologies that promote the clean and efficient use of energy in India; and (5) technical assistance in support of the development by the Government of India of a strategic oil reserve to allow India to cope with short-term disruptions to global oil supplies without causing shocks to India's market or the global market. SEC. 5. REPORT ON ENERGY COOPERATION. (a) In General.--Not later than 180 days after the date of the enactment of this Act, the Secretary of State shall, in coordination with the Secretary of Energy, submit to the Committee on Foreign Relations and the Committee on Energy and Natural Resources of the Senate and the Committee on Energy and Commerce and the Committee on International Relations of the House of Representatives a report on energy security cooperation between the United States and India. (b) Content.--The report required under subsection (a) shall describe-- (1) the ways in which the United States and India have cooperated on energy research and development activities; (2) joint projects that have been initiated using assistance authorized under section 4, and the contribution such assistance has made to improving global energy security; and (3) plans for future energy cooperation and joint projects between the United States and India.

United States-India Energy Security Cooperation Act of 2006 - Authorizes the President to establish programs in support of greater energy cooperation between the United States and India. Authorizes assistance for cooperation related to research, development, and deployment in selected areas, including: (1) clean coal and emission reduction technologies and carbon sequestration projects; (2) alternative fuel sources, such as ethanol, biomass, coal-based fuels, and hydrogen; and (3) energy efficiency projects.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Revolving Door Act of 1995''. SEC. 2. SPECIAL RULES. (a) In General.--Section 207(d) of title 18, United States Code, is amended by adding at the end thereof the following: ``(3) Additional restrictions.-- ``(A) Lobbying legislative branch by executive branch officials and appointees.--In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection, any person who-- ``(i)(I)) serves in the position of President or Vice President of the United States, or ``(II) serves in a position in an executive agency (including the Executive Office of the President) on a full-time basis and whose rate of basic pay is not less than $70,000 (adjusted for any COLA after the date of enactment of the Revolving Door Act of 1995), and ``(ii) is not an appointee of the senior foreign service or solely an appointee as a uniformed service commissioned officer, and who, during the 2 years after termination of service or employment as such an official or appointee, knowingly makes, with the intent to influence, any communication to or appearance before any Member, officer, or employee of either House of Congress or any employee of any other legislative office of Congress on behalf of any other person (except the United States) in connection with any matter on which such former official or appointee seeks action by such a Member or officer or employee acting in the Member's, officer's, or employee's official capacity shall be punished as provided in section 216 of this title. ``(B) Lobbying legislative branch by former members.--In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection, any person who is a Member of Congress and who-- ``(i) during the 2 year period after termination of such service, knowingly makes, with the intent to influence, any communication to or appearance before any Member, officer, or employee of either House of Congress or any employee of any other legislative office of Congress on behalf of any other person (except the United States) in connection with any matter on which such former Member seeks action by such a Member or officer or employee acting in the Member's, officer's, or employee's official capacity, or ``(ii) during the 5 year period after termination of such service, knowingly makes, with the intent to influence, any communication to or appearance before any Member or employee of the House of Congress in which such former Member served who is a member of or employed by the committee on which such former Member served on behalf of any other person (except the United States) in connection with any matter on which such former Member seeks action by such a Member or employee acting in the Member's or employee's official capacity shall be punished as provided in section 216 of this title. ``(C) Lobbying legislative branch by former legislative employees.--In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection-- ``(i) any person who is an officer or employee of either House of Congress employed in a position at a rate of pay equal to or greater than $70,000 (adjusted for any COLA after the date of enactment of the Revolving Door Act of 1995) and who during the 2 year period after termination of such service, knowingly makes, with the intent to influence, any communication to or appearance before any Member, officer, or employee of either House of Congress or any employee of any other legislative office of Congress on behalf of any other person (except the United States) in connection with any matter on which such former officer or employee seeks action by such a Member or officer or employee acting in the Member's, officer's, or employee's official capacity, or ``(ii) any person who was an employee of either House of Congress employed in a position at a rate of pay equal to or greater than $70,000 (adjusted for any COLA after the date of enactment of the Revolving Door Act of 1995) and who during the 5 year period after termination of such service, knowingly makes, with the intent to influence, any communication to or appearance before any Member or employee of the House of Congress in which such former employee served who is a member of or employed by the committee which employed such former employee on behalf of any other person (except the United States) in connection with any matter on which such former employee seeks action by such a Member or employee acting in the Member's or employee's official capacity shall be punished as provided in section 216 of this title. ``(D) Lobbying the executive branch by former members or former legislative employees.--In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection, any person who is described in subparagraph (B) or (C) and who during the 2 years after termination of service as a Member or employee, knowingly makes, with the intent to influence, any communication to or appearance before any officer or employee of a department or agency on behalf of any other person (except the United States) in connection with any matter on which such former Member or employee seeks official action by any officer or employee of such department or agency, shall be punished as provided in section 216 of this title. ``(E) Lobbying the executive branch by executive branch officials and employees.--In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection, any person who-- ``(i)(I)) serves in the position of President or Vice President of the United States, or ``(II) serves in a position in an executive agency (including the Executive Office of the President) on a full-time basis and whose rate of basic pay is not less than $70,000 (adjusted for any COLA after the date of enactment of the Revolving Door Act of 1995), and ``(ii) is not an appointee of the senior foreign service or solely an appointee as a uniformed service commissioned officer, and who, during the 2 years after termination of service or employment as such an official or appointee, knowingly makes, with the intent to influence, any communication to or appearance before any officer or employee of a department or agency, during the period beginning on the termination of service or employment as such officer or employee and ending 2 years after the termination of service in the department or agency, on behalf of any other person (except the United States), in connection with any matter on which such person seeks official action by any officer or employee of such department or agency, shall be punished as provided in section 216 of this title. ``(F) Lobbying a particular department or agency by executive branch officials and employees.--In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection, any person who is described in subparagraph (E) and who, during the 5 years after termination of service or employment as such an official or appointee, knowingly makes, with the intent to influence, any communication to or appearance before any officer or employee of a department or agency, in which such person served within 5 years before such termination, during the period beginning on the termination of service or employment as such officer or employee and ending 5 years after the termination of service in the department or agency, on behalf of any other person (except the United States), in connection with any matter on which such person seeks official action by any officer or employee of such department or agency, shall be punished as provided in section 216 of this title. ``(G) Supervision of lobbyists.--Any person who is in a position described in subparagraph (B) or (C) may not knowingly, after leaving such position, hold a supervisory position over any person who is likely to make a communication or appearance described in subparagraph (B) or (D). ``(H) Ban.--Any person who was a Member of Congress and who is convicted of a felony may not make any communication or appearance described in subparagraph (B) or (D).''. (b) Conforming Amendments.-- (1) Section 207(d).--Section 207(d)(1)(A) of title 18, United States Code, is amended to read as follows: ``(A) serves in the position of President or Vice President of the United States,''. (2) Section 207(h).--The first sentence of section 207(h)(1) of title 18, United States Code, is amended by inserting after ``subsection (c)'' the following: ``and subsection (d)(3)''. (3) Section 207(e).--Section 207(e)(7) is amended by inserting before the dash the following: ``and subsection (d)''. (c) Foreign Agents.--Section 207(f) of title 18, United States Code, is amended-- (1) by striking ``foreign entity'' each place it appears and inserting ``foreign national''; and (2) by striking paragraphs (2) and (3) and inserting: ``(2) Lobbying on behalf of a foreign national.--(A) In addition to the restrictions set forth in subsections (a), (b), and (c) and paragraph (1) of this subsection, any person who is in a position described in subparagraph (B) or (C) of subsection (d)(3) and who knowingly, after leaving such position-- ``(i) represents, directly or indirectly, a foreign national before any officer or employee of any department or agency of the United States or any Member of Congress or officer or employee of either House of Congress with the intent to influence a decision of such officer or employee of the United States or Member of Congress or officer or employee of either House of Congress in carrying out the Member's, officer's, or employee's official duties and receives compensation for such representation, or ``(ii) aids or advises, directly or indirectly, a foreign national with the intent to influence a decision of any officer or employee of any department or agency of the United States or any Member of Congress or officer or employee of either House of Congress in carrying out the Member's, officer's, or employee's official duties and receives compensation for such aid or advice, shall be punished as provided in section 216 of this title. ``(3) For purposes of subparagraph (A), the term `foreign national' means-- ``(A) a government of a foreign country as defined in section 1(e) of the Foreign Agents Registration Act of 1938, as amended, or a foreign political party as defined in section 1(f) of that Act; ``(B) a person outside of the United States, unless such person is an individual and a citizen of the United States, or unless such person is not an individual and is organized under or created by the laws of the United States or of any State or other place subject to the jurisdiction of the United States and has its principal place of business within the United States; ``(C) a partnership, association, corporation, organization, or other combination of persons organized under the laws of or having its principal place of business in a foreign country; or ``(D) a person any of whose activities are directly or indirectly supervised, directed, controlled, financed, or subsidized in whole or in major part by an entity described in subparagraph (A), (B), or (C).''. (d) Exceptions.--Section 207(j) of title 18, United States Code, is amended by adding at the end thereof the following: ``(7) Non-influential contacts.--Nothing in this section shall prevent an individual from making requests for appointments, requests for the status of Federal action, or other similar ministerial contacts, if there is no attempt to influence an officer or employee of the legislative or executive branch. ``(8) Comments.--Nothing in this section shall prevent an individual from making communications in response to a notice in the Federal Register, Commerce Business Daily, or other similar publication soliciting communications from the public and directed to the agency official specifically designated in the notice to receive such communications. ``(9) Adjudication.--Nothing in this section shall prevent an individual from making communications or appearances in compliance with written agency procedures regarding an adjudication conducted by the agency under section 554 of title 5, or substantially similar provisions. ``(10) Comments for the record.--Nothing in this section shall prevent an individual from submitting written comments filed in a public docket and other communications that are made on the record.''. (e) Use of Profits.--Section 216(b) of title 18, United States Code, is amended by inserting after the first sentence the following: ``Any amount of compensation recovered pursuant to the preceding sentence for a violation of section 207 shall be deposited in the general fund of the Treasury to reduce the deficit.''. SEC. 3. LIMITATION ON CONTRIBUTION OF EXCESS CAMPAIGN FUNDS. Section 313 of the Federal Election Campaign Act of 1971 (2 U.S.C. 439a) is amended by adding at the end the following new sentence: ``An individual who has excess campaign funds and is neither a candidate for, nor an incumbent of, a Federal office and who is registered under the Federal Regulation of Lobbying Act may not make any contribution from such excess campaign funds to another individual who is a candidate for Federal office or to any authorized committee of such other individual.''. SEC. 4. FLOOR PRIVILEGES. Rule XXXII of the Rules of the House of Representatives is amended by striking ``only if they'' and inserting ``only if they are not lobbyists,''. SEC. 5. ADDITIONAL PRIVILEGES. Any former Member of Congress who is registered under the Federal Regulation of Lobbying Act shall not be permitted to enter any dining area of the Capitol which is reserved for Members of Congress or any gymnasium facility which is reserved for Members of Congress.

Revolving Door Act of 1995 - Amends the Federal criminal code to set forth new provisions prohibiting public officials, within a specified period following termination of their public service, from knowingly making, with intent to influence, any communication or appearance before congressional or executive branch officials or employees, on behalf of any other person seeking official action (lobbying). Prohibits the following individuals, for two years after termination of their service or employment, from lobbying any Member, officer, or employee of Congress: (1) the President or Vice President; (2) Members of Congress; (3) individuals who serve in executive agency positions on a full-time basis, who have a rate of basic pay of at least $70,000, and who are not appointees of the senior foreign service or as uniformed service commissioned officers; and (4) officers or employees of Congress with a rate of pay of $70,000 or above. Prohibits: (1) Members of Congress, the President or Vice President, such executive branch employees, or such congressional employees, for two years after termination of their service or employment, from lobbying any officer or employee of an executive department or agency; (2) Members of Congress or such congressional employees, for five years after termination of their service, from lobbying any congressional committee Members or employees who are members of, or employed by, the committee on which such former Members served or for which such employee worked; or (3) the President, Vice President, or such executive branch employees, for five years after termination of their service or employment, from lobbying any officer or employee of the department or agency in which such person served. Prohibits such a Member, officer, or employee of the Congress from knowingly, after leaving such position, holding a supervisory position over any person who is likely to lobby Congress or executive agencies. Bans any former Member of Congress who is convicted of a felony from lobbying. Applies restrictions on lobbying on behalf of foreign entities to lobbying on behalf of foreign nationals. Prohibits such a Member, officer, or employee of Congress, after leaving such office, from lobbying on behalf of a foreign national for compensation. Provides that nothing in this Act shall prevent an individual from: (1) making requests for appointments, status of Federal action, or other similar ministerial contacts if there is no attempt to influence an officer or employee of the legislative or executive branch; (2) making communications in response to a notice in the Federal Register, Commerce Business Daily, or other similar publication soliciting communications from the public and directed to the agency official specifically designated in such notice; (3) making communications or appearances in compliance with written agency procedures regarding an adjudication conducted by an agency under adjudication provisions; or (4) submitting written comments filed in a public docket and other communications that are made on the record. Requires compensation recovered pursuant to imposition of a civil penalty upon former officers, employees, and elected officials of the executive and legislative branches for violation of lobbying restrictions to be deposited in the Treasury for deficit reduction. (Sec. 3) Amends the Federal Election Campaign Act of 1971 to prohibit an individual who has excess campaign funds and is neither a candidate for, nor an incumbent of, a Federal office and who is registered under the Federal Regulation of Lobbying Act from making any contribution from such excess campaign funds to another individual who is a candidate for Federal office or to any authorized committee of such other individual. (Sec. 4) Amends rule XXXII of the Rules of the House of Representatives to prohibit lobbyists from being entitled to the privilege of admission to the Hall of the House and rooms leading thereto. (Sec. 5) Prohibits any former Member of Congress who is registered under the Federal Regulation of Lobbying Act from being permitted to enter any dining area of the Capitol or any gymnasium facility which is reserved for Members.

visual observers reported detection of zonal bands and occasional spots on uranus as early as 1870 @xcite , but a reliable measure of atmospheric motions on uranus had to wait until 1986 , when close - up voyager-2 images revealed eight discrete cloud features between planetocentric latitudes of 35s and 70s @xcite . tracking these features , combined with one radio occultation wind measurement at 5s , yielded a crude zonal wind profile @xcite , the main feature of which appeared to be a high - speed ( @xmath1250 m / s ) prograde jet near 60s and a weaker broad retrograde equatorial jet . voyager did not provide wind information in the northern hemisphere , which was near its winter solstice and dark at the time of the encounter . eleven years later , hubble space telescope ( hst ) near - ir images of uranus revealed many more discrete cloud features , enabling the extension of wind measurements into the northern hemisphere @xcite , confirming an approximate n - s symmetry in the wind profile . groundbased observations from the keck ii telescope , which combined a large aperture , near - ir wavelengths , and adaptive optics , produced a bounty of cloud features far beyond the hubble results @xcite . the wind profile of uranus was last updated by @xcite , combining wind observations from the above references with new measurements in 2009 - 2011 from gemini , keck , and hst observatories . here we use as a reference their 13-term asymmetric legendre fit given in their table 6 and plotted in their fig . 11 . this will be hereafter referred to as model * s13a*. the main results enabled by their new measurements were : ( 1 ) clear definition of the magnitude and latitude of the northern jet peak ; ( 2 ) discovery that motions north of the peak were consistent with solid body rotation ; ( 3 ) discovery of a new class of cloud features in the polar regions that resemble cumulus cloud fields and bear similarities to the cloud structure in the polar regions of saturn ; and ( 4 ) characterization of the large morphological asymmetry between southern summer polar latitudes and northern spring polar latitudes . the updated profile still suffered from a lack of targets in low latitudes ( 20s - 20n ) and in the south polar region , where , save for one uv feature identified by voyager , no discrete clouds had ever been seen . the @xcite work was advanced by the use of high s / n techniques to improve detectability and facilitate tracking of low contrast cloud features . the basic idea was to use long exposures to grow the signal linearly in exposure time while random noise grew as the square root , thus increasing s / n as the square root of the exposure time . to avoid the smearing of long exposures by planetary rotation , we took multiple short exposures , rotated the planet images to the same central meridian longitude , then averaged the de - rotated images . @xcite verified this process using keck imagery and applied it to specially designed hst imaging to provide new wind measurements . @xcite applied it to gemini imaging in 2011 , and to a limited degree to keck imaging in 2011 , though highly variable seeing limited the benefits that were possible . much improved results were obtained from subsequent observations with better seeing that resulted in better ao performance . the 2012 results shown in fig . [ fig : bestim ] , first presented by @xcite and @xcite , were the most detailed images of uranus ever obtained up to that time . features revealed by those images are discussed in section [ sec : patterns ] . 8.5n ( planetographic ) , the scalloped waveform centered near 4.5s , and the ribbon wave near 6s . note the narrow bright latitude bands spaced about 2.5apart in the 48 - 53range , and the numerous small bright spots north of 55n . the bright narrow feature in the southern hemisphere is the epsilon ring of uranus.,width=316 ] since 2007 , our view of the north polar region of uranus improved significantly : at opposition , the the sub - solar latitude reached 19.5n in 2012 , 23.5n in 2013 , and 27.6n in 2014 . this resulted in observations well suited to further refinement of the zonal wind profile in the northern hemisphere and better characterization of its polar cloud features . it also helped to fill in poorly sampled regions , mainly at low latitudes . fortunate periods of high quality seeing also allowed us to apply high s / n techniques more extensively and thereby detect and track more subtle features . in the following we describe the new observations , the measurement results from each data set , new views of the north polar region of uranus and the different styles of discrete cloud features located there , new features discovered at low latitudes , and finally , approximate altitude constraints on the cloud features . table [ tbl : obslist ] summarizes keck and gemini imaging observations of uranus acquired from 2012 through 2014 . the camera characteristics for each groundbased observing configuration are given in table [ tbl : cameras ] , in which the pixel scale of [email protected] arcsec / pixel listed for the gemini niri camera was derived from measurements of uranus and its satellites in comparison with horizons ephemeris positions , as described by @xcite . we used the keck ii / nirc2 pixel scale provided by the keck observatory web site , which we found to be consistent with measurements of the uranian ring system . for gemini ao operation , we used a bright uranian satellite ( usually ariel ) as the wavefront reference , while for keck ii ao operation we were able to use uranus itself , providing a substantial gain in reference object brightness ( vmag=5.6 vs. vmag@xmath414 ) and thus in image quality for similar seeing conditions . except for the image s / n enhancement , described in more detail by @xcite , image processing and navigation followed the same procedures described by @xcite . to aid in long - term tracking of a long lived feature that was first observed in august 2014 ( identified as f in a later section ) , we also used non - proprietary images from hst program 13712 ( target of opportunity observation of an episodic storm on uranus , pi k. sayanagi ) and hst program 13937 ( hubble 2020 : outer planet atmospheres legacy ( opal ) program , pi a. simon ) . c c c c c c c l + date & time range & telescope / camera / program & pi & filters ( images ) + + 2012/07/25 & 09:59 - 12:29 & keck / nirc2/2012a - n145n2 & las & h(93 ) , hc(24 ) , k@xmath3(1 ) + 2012/07/26 & 10:04 - 15:29 & keck / nirc2/2012a - n145n2 & las & h(88 ) , hc(32 ) + 2012/08/16 & 10:31 - 15:41 & keck / nirc2/2012b - n125n2 & las & h(91 ) , hc(56 ) + 2012/09/28 & 08:20 - 12:24 & gemini - n / niri / gn-2012b - q-121 & las & h(11 ) , hc(10 ) + 2012/09/30 & 08:15 - 12:09 & gemini - n / niri / gn-2012b - q-121 & las & h(8 ) , hc(9 ) + 2012/10/04 & 08:58 - 12:50 & gemini - n / niri / gn-2012b - q-121 & las & h(11 ) , hc(12 ) + 2012/10/09 & 06:17 - 10:10 & gemini - n / niri / gn-2012b - q-121 & las & h(11 ) , hc(11 ) + 2012/11/04 & 04:17 - 09:34 & keck / nirc2/2012b - u011n2 & idp & h(120 ) , hc(3 ) , k@xmath3(1 ) + 2012/11/05 & 04:11 - 09:17 & keck / nirc2/2012b - u011n2 & idp & h(42 ) , hc(76 ) , k@xmath3(2 ) + 2013/08/15 & 10:35 - 14:43 & keck / nirc2/2013b - u009n2 & idp & h(74 ) , ch4s(10 ) , k@xmath3(3 ) + 2013/08/16 & 10:34 - 15:24 & keck / nirc2/2013b - u009n2 & idp & h(84 ) , ch4s(14 ) , k@xmath3(10 ) + 2014/08/05 & 11:34 - 15:36 & keck / nirc2/2014b - u037n2 & idp & h(64 ) , k@xmath3(5 ) , ch4s(8 ) + 2014/08/06 & 11:24 - 13:44 & keck / nirc2/2014b - u037n2 & idp & h(78),j(1),k@xmath3(9),ch4s(10 ) + 2014/08/20 & 13:38 - 13:44 & keck / nirc2/2014b - u014n2 & idp & h(2 ) , k@xmath3(2 ) + 2014/10/30 & 08:57 - 09:03 & gemini - n / niri / gn-2014b - dd-5 & las & h(4 ) + 2014/11/09 & 09:19 - 09:25 & gemini - n / niri / gn-2014b - dd-5 & las & h(4 ) + 2014/11/26 & 07:14 - 07:48 & gemini - n / niri / gn-2014b - dd-5 & las & h(4 ) , k@xmath3(4 ) , hc(8 ) + 2015/01/08 & 07:05 - 07:24 & gemini - n / niri / gn-2014b - dd-5 & las & h(4 ) , k@xmath3(4 ) , hc(8 ) + + [ tbl : obslist ] c c c c c c + & mirror & & pixel & diff . limit & + telescope & diam . & camera & size & @ wavelength + + gemini - n & 8 m & niri & 0.02138@xmath5 & 0.05@xmath5 @ 1.6 + keck ii & 10 m & nirc2-na & 0.00994@xmath5 & 0.04@xmath5 @ 1.6 + + [ tbl : cameras ] almost all our observations were designed for high s / n imaging and were successful to varying degrees , mainly dependent on seeing conditions . a sampling of the mosaicked and averaged h - band images from the keck and gemini data sets is provided in fig . [ fig : imsamples ] . most of these images were averaged in groups of eight 2-minute exposures . the exceptions are for the gemini images in which all images during the night were averaged together ( this required removal of approximate zonal wind displacements as well as planet rotation ) . in fig . [ fig : imsamples ] each image is followed by a version with enhanced small - scale feature contrast , obtained by replacing the original image i by i+30@xmath6(i - smooth(i ) ) , using a smoothing length of 0.13@xmath5 ( 13 pixels in keck images ) . in most cases the keck ao images provide a level of detail far superior to that obtained from gemini or hst . in one case , however , a fortuitous natural seeing of 0.37@xmath5 resulted in an excellent gemini image ( g and h in fig . [ fig : imsamples ] ) , providing slightly better s / n though at a slightly lower resolution ( see fig . [ fig : imsamples]g ) . many of these images reveal a low - latitude waveform just south of the equator , the best examples of which are seen in fig . [ fig : imsamples ] , panels b ( 25 july 2012 ) and j ( 4 november 2012 ) . the wave is also evident in several other images , including the gemini image from 4 october 2012 . when first observed in 2012 , it was suggested that this might be an unstable feature because of morphological similarities to unstable waves in high - shear regions . the persistence of the waveform , and the lack of evidence for high ( or any ) zonal wind shear in the region of the wave , suggests that other explanations might be needed . these images also show a persistence of small cloud features at high northern latitudes , although the contrast of these features in the 2014 images seems to be reduced , perhaps by a developing haze in the north polar region @xcite ( note the brighter near - pole region in 2014 relative to that in 2012 ) . there is a general lack of discrete cloud features south of 30n , with the striking exception of 2014 images ( fig . [ fig : imsamples]q - t ) , which not only display numerous cloud features in this region , but also several unusually bright ones , including the brightest ever seen in k@xmath3 images @xcite , and the second brightest ever seen in h - band images . the brightest feature in h - band images @xcite was seen in 2005 at a planetographic latitude of 31n . we also acquired hcont images in groups of 12 ( for keck observations ) . images with the hcont filter ( not shown ) differ from the h - filter images in having relatively brighter mid latitudes , more noise ( due to less throughput in the narrow - band filter ) , generally lower contrast , and fewer visible cloud features . the average penetration depths of light within these filter bands into a clear uranus atmosphere are shown in fig . [ fig : penprof ] . the different vertical weighting of hcont images allows the combination of h and hcont images to constrain the vertical location of cloud features . limited imaging with ch4s and k@xmath3 filters provided additional constraints , which are all discussed in section [ sec : vertical ] . we used maximum correlation tracking , as described by @xcite , to maximize the number of cloud targets that could be usefully tracked and to reduce errors in position measurements . we displayed an image sequence as a stacked series of narrow horizontal strips , each containing a rectangular projection covering a specified range of longitudes and a narrow range of latitudes , using [email protected] pixels , as illustrated in fig . [ fig : scrnshot1 ] . for each cloud target visible in the selected latitude range , a reference image is selected and a target box is adjusted in size and position in the reference image so that the box contains the cloud feature and a small region outside of it . target boxes in other images are initially positioned using _ a prior _ wind profile ; then the guess is manually adjusted as needed to insure that all target boxes contain the target feature . the positions of the target boxes in all but the reference images are then automatically precision - adjusted to maximize the cross correlation between the reference target box signal variations and those contained in each of the other boxes . the correlation coefficient @xmath7 was computed using @xmath8 where @xmath9 and @xmath10 are brightness values at the @xmath11th pixel location in images @xmath12 and @xmath13 respectively , @xmath14 and @xmath15 their average values , and the summation is over all corresponding pixels in the target boxes . to reduce the impact of large - scale variations such as produced by latitude bands , we use high - pass filters to display local contrast and remove large - scale image slopes before correlation . measurements of longitude and latitude vs. time were fit to straight lines using both unweighted and weighted fits , and assigned errors that were the larger of the two estimates obtained from linear regression . the results are produced in real time as each target is tracked and displayed as illustrated in fig . [ fig : scrnshot1 ] . errors in latitude and longitude are estimated in two ways . the first is an a priori computation of the scaled root sum of squared errors produced by displacements of one image pixel in both dimensions . these errors , which provide the basis for the weighted fits , vary appropriately with view angle and position on the disk and are important when the number of samples is small . but , when the number of samples is large , the second and more accurate error estimate is computed from the rms deviation of the measurements from a straight line fit , as it includes both navigation errors as well as target identification and tracking errors . this second estimate provides the basis for the unweighted fits . we made over 850 measurements of cloud feature drift rates in the 2012 - 2014 images , mostly tracking small discrete cloud features , with each drift rate based on from 3 to 11 individual position measurements . for comparison , the voyager mission returned only 8 wind measurements @xcite and the recent extensive reanalysis of voyager images by @xcite yielded 27 trackable discrete features . the keck data from 2014 provided an exceptional number of measurements , which is a result of the increased activity of uranus in 2014 , not due to exceptional image quality . in fact , image quality during the 5 - 6 august observing run was a little below par for our typical keck ii observations . the distribution of measurements in longitude and latitude segregated by data set is provided in fig . [ fig : distribution ] . as can be seen from this figure and the plot of statistical properties in fig . [ fig : mstats ] , the measurements are heavily weighted to the northern hemisphere , where discrete cloud targets are most numerous . furthermore , because the sub - earth and sub - solar points are in the northern hemisphere , the cloud features there are visible over a longer time span during a given observing night than is possible at southern latitudes . consequently , even were the distribution of targets uniform , there would still be more measurements and more accurate measurements in the northern hemisphere . especially numerous were cloud features north of 45n . not surprisingly , these data sets provided no observations below about 40s . the distribution of wind measurements over a wide range of longitudes for most data sets achieves a major objective of our high s / n observing program , i.e. to avoid having wind results dominated by a few large features and features in their immediate surroundings , which might be generated by the large feature and travel along with it , even at a different latitude . [ fig : distribution ] also classifies each drift rate measurement according to median correlation of the set of position measurements used to determine the drift rate . the darker the plotted point , the higher the median correlation , and the more likely the cloud did not evolve much during the tracked interval , and was elevated above the noise level , improving the accuracy of the position tracking . most of the measurements obtained median correlation peaks that were between 0.8 and 1 ( fig . [ fig : mstats]e ) . near - equatorial features that appear to be associated with waves had some of the lowest median correlation peaks ( 0.4 - 0.6 ) . discrete cloud features were tracked in sequences of up to eleven images , always in at least three , and most in 5 - 9 image sequences . the standard deviation of latitude measurements for a given cloud target ( fig . [ fig : mstats]b ) was usually within one or two map pixels ( 0.2/pixel ) , as were longitude measurements , which were all determined by correlation . most features were tracked using target boxes between 3and 10 in longitude and 2 - 5 in latitude ( fig . [ fig : mstats]e - f ) . for compact features both latitude and longitude positions of the cloud boxes were determined by correlation , which was done to compensate for small navigation errors between images . but navigation errors are responsible for only part of the dispersion in latitude measurements . the remainder is due to evolution in cloud target morphology over time , and to some degree it may be due to latitudinal drifts and/or oscillations , though it is only tracking over long time intervals that revealed any statistically significant latitudinal motion . figure [ fig : mstats ] also shows that a subset of our measurements used correlation boxes that were wide ( in longitude ) and narrow ( in latitude ) , which were designed to group together a number of nearby features at the same latitude to allow a more precise determination of their group drift rate within a single transit . these were usually 1.2 in latitude and 50 - 100 in longitude . for these boxes we did correlation tracking of only the longitudinal displacement to avoid latitude shifts due to the brightest cloud feature included . a key factor in the resulting accuracy of the wind measurement was the length of time that a target could be tracked ( fig . [ fig : mstats]h ) . the shortest time that we considered even marginally useful was one hour . typically the best we could obtain within a single night of observing was a little over 4 hours . when a feature could be identified on successive nights , which was possible mostly only for higher - latitude features , wind accuracy improved dramatically . for some targets tracked in gemini data sets we were able to track targets over a span of several hundred hours ( with significant coverage gaps of course ) . even longer tracking times were achieved for six persistent discrete features identified mainly in keck imagery and discussed in section [ sec : long ] . the measurements of the westward drift rate relative to the planet s longitude system are plotted in fig . [ fig : driftplot1 ] , where the full data set of 852 measurements is shown in panel a and a subset including only the 163 most accurate measurements in panel b. these two samples are both compared to the model s13a , shown as a solid curve , and its reflection about the equator shown as the dotted curve . points falling on the solid curve would tend to confirm the asymmetry previously inferred . points between the solid and dotted curves would be more consistent with hemispheric symmetry . since many of our points fall between these two curves , they suggest somewhat less asymmetry than the prior fit . a more detailed analysis of asymmetry is discussed in section [ sec : asymm ] . the largest discrepancies between our new observations and the prior legendre polynomial fit are near the equator and at high latitudes ( fig . [ fig : driftplot1 ] ) . in the north polar region , we find a very robust determination of solid body rotation between 62n and 83n , with a westward rotation rate of 4.1/h relative to the planet s interior rotation rate of 360/17.24h ( = 20.88/h ) . that corresponds to a rotational period of 14.41 hours . the prior legendre polynomial fit has a relative solid body rotational period of 4.3/h , which is less accurate because of fewer measurements , shorter time tracks , and poorer views of high latitudes . the second discrepancy with the prior wind profile occurs within 6of the equator . measurements with the highest accuracy , based on small discrete clouds of high contrast in 2014 images , yield a very small longitudinal drift of 0.1/h eastward between 1n and 5s , while the legendre fit suggests a drift rate of about 0.4/h to the east . that latter drift rate is more compatible with our lower accuracy measurements in this region , which are based on much more diffuse low - contrast features that have relatively low median correlations , or on wave patterns , such as the nearly sinusoidal dark ribbon visible in several of the images in fig . [ fig : imsamples ] . it is clear that the wave features drift eastward at close to four times the rate observed for the small discrete features tracked in 2014 . drift rates similar to those measured for wave features in our 2012 - 2014 observations were also observed by @xcite , who found , in their 2003 images of uranus , `` fuzzy patches '' within 2of the equator moving with an average eastward velocity of 47 m / s , or 0.38/h eastward . similar features measured by @xcite 2 - 3north of the equator , were found to move eastward at a rate of 0.51/h . interestingly , @xcite found the features to have roughly a 40spacing in longitude , while @xcite found a 30spacing , but with gaps . the features in our 2012 - 2014 observations seem to be near 36 , and not quite twice the period of the ribbon wave . ( this is presented in section [ sec : waves ] . ) these high s / n images indicate that not all the equatorial features match the average spacing of 36 ; some have considerably different spacings . there are also gaps and regions where features are spread out and difficult to locate . it is not clear that the wave producing these features extends entirely around the planet . the variability of these features may explain the discrepancies between prior measurements of their spacings . selecting only the high - accuracy observations leaves significant gaps in latitude coverage . to fill in those gaps we average observations within latitude bins , using the estimated variance of each observation as its weight in computing a weighted average . the results for 2bins are shown in fig . [ fig : bin1 ] and tabulated in tables [ tbl : northbin ] and [ tbl : southbin ] . this procedure does indeed fill in many of the missing latitudes in the high - accuracy subset . the estimated error of the weighted average measurements is so small in most bins that it is within the plotted symbol . the region of solid body rotation is seen to be very uniform in these binned results . between 65n and 83n , we obtain an average of the binned measurements of 4.079/h with a standard deviation of 0.015/h , compared to a range of weighted average expected errors of .002 - 0.022/h . near the equator , binned results display significant scatter . just north of the equator , the binned results are in rough agreement with the old ( s13a ) wind profile . but just south of the equator , the high accuracy winds from small high - contrast features has dominated the winds inferred from larger scale low contrast and wave features . an odd feature of the binned results is that the wind profile in the region from about 18n to 45n seems to have a sequence of stair steps of local solid body rotation extending for a few degrees with sharp , high shear transitions between them . it could very well be the case that the zonal wind profile of uranus is simply not a very smooth function of latitude . we also tried binning at 1intervals , and found the same stair - step structure between 10n and 30n , but hints of that structure at other latitudes were no longer evident , perhaps due to increased variability . the north polar region of solid - body rotation was largely unchanged by reducing the bin size , except for small increases in noise due to reduced numbers of samples per bin . no fundamentally new structures ( that could be distinguished from noise ) were found in the wind profile by using smaller bin sizes of 1or 0.5 . c c c c c c c + & drift rate & std . dev . & wind speed & bin + center & avg . & std . dev . & e / h & /h & m / s & count + + 85 & 84.58 & 0.41 & [email protected] & 0.32 & [email protected] & 2 + 83 & 82.24 & 0.44 & [email protected] & 0.13 & [email protected] & 12 + 81 & 80.84 & 0.32 & [email protected] & 0.39 & [email protected] & 9 + 79 & 78.23 & 0.15 & [email protected] & 1.00 & [email protected] & 6 + 77 & 76.11 & 0.58 & [email protected] & 0.36 & [email protected] & 11 + 75 & 75.16 & 0.69 & [email protected] & 0.31 & [email protected] & 24 + 73 & 73.51 & 0.50 & [email protected] & 0.26 & [email protected] & 48 + 71 & 71.00 & 0.60 & [email protected] & 0.52 & [email protected] & 12 + 69 & 68.74 & 0.66 & [email protected] & 0.28 & [email protected] & 23 + 67 & 66.93 & 0.64 & [email protected] & 0.18 & [email protected] & 51 + 65 & 65.23 & 0.59 & [email protected] & 0.24 & [email protected] & 49 + 63 & 63.41 & 0.51 & [email protected] & 0.22 & [email protected] & 39 + 61 & 61.30 & 0.49 & [email protected] & 0.18 & [email protected] & 22 + 59 & 59.11 & 0.56 & [email protected] & 0.14 & [email protected] & 21 + 57 & 57.33 & 0.43 & [email protected] & 0.15 & [email protected] & 22 + 55 & 55.16 & 0.41 & [email protected] & 0.07 & [email protected] & 3 + 53 & 52.34 & 0.18 & [email protected] & 0.15 & [email protected] & 11 + 51 & 50.77 & 0.48 & [email protected] & 0.20 & [email protected] & 45 + 49 & 48.42 & 0.50 & [email protected] & 0.23 & [email protected] & 46 + 47 & 47.34 & 0.54 & [email protected] & 0.22 & [email protected] & 40 + 45 & 44.54 & 0.53 & [email protected] & 0.16 & [email protected] & 17 + 43 & 42.38 & 0.57 & [email protected] & 0.22 & [email protected] & 11 + 41 & 40.95 & 0.41 & [email protected] & 0.15 & [email protected] & 15 + 39 & 39.05 & 0.46 & [email protected] & 0.11 & [email protected] & 17 + 37 & 37.67 & 0.53 & [email protected] & 0.19 & [email protected] & 25 + 35 & 35.60 & 0.34 & [email protected] & 0.13 & [email protected] & 12 + 33 & 33.43 & 0.53 & [email protected] & 0.14 & [email protected] & 21 + 31 & 30.14 & 1.07 & [email protected] & 0.13 & [email protected] & 4 + 29 & 28.89 & 0.21 & [email protected] & 0.15 & [email protected] & 3 + 27 & 26.26 & 0.26 & [email protected] & 0.15 & [email protected] & 4 + 25 & 25.21 & 0.53 & [email protected] & 0.17 & [email protected] & 26 + 23 & 23.27 & 0.62 & [email protected] & 0.33 & [email protected] & 11 + 21 & 20.38 & 0.53 & [email protected] & 0.17 & [email protected] & 13 + 19 & 19.19 & 0.51 & [email protected] & 0.22 & [email protected] & 12 + 17 & 17.05 & 0.64 & [email protected] & 0.15 & [email protected] & 14 + 15 & 15.70 & 0.62 & [email protected] & 0.16 & [email protected] & 6 + 13 & 12.85 & 0.56 & [email protected] & 0.09 & [email protected] & 3 + 7 & 6.17 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + 5 & 5.04 & 0.39 & [email protected] & 0.12 & [email protected] & 3 + 3 & 2.31 & 0.74 & [email protected] & 0.12 & [email protected] & 11 + 1 & 1.51 & 0.41 & [email protected] & 0.23 & [email protected] & 20 + [ tbl : northbin ] c c c c c c c + & drift rate & std . dev . & wind speed & bin + center & avg . & e / h & /h & m / s & count + + -3 & -3.02 & 0.74 & [email protected] & 0.30 & -17.2@xmath2 1.4 & 17 + -5 & -5.38 & 0.48 & [email protected] & 0.23 & -47.3@xmath2 1.1 & 39 + -7 & -6.49 & 0.45 & [email protected] & 0.36 & -8.8@xmath2 7.7 & 4 + -11 & -11.30 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -15 & -14.60 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -17 & -16.68 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -19 & -18.56 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -21 & -21.24 & 0.35 & [email protected] & 0.36 & [email protected] & 2 + -23 & -23.36 & 0.47 & [email protected] & 0.37 & [email protected] & 3 + -25 & -24.55 & 0.56 & [email protected] & 0.25 & [email protected] & 3 + -27 & -26.03 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -29 & -29.43 & 0.41 & [email protected] & 0.19 & [email protected] & 5 + -31 & -30.61 & 0.45 & [email protected] & 0.11 & [email protected] & 4 + -33 & -33.17 & 0.82 & [email protected] & 0.19 & [email protected] & 2 + -35 & -34.67 & 0.25 & [email protected] & 0.20 & [email protected] & 2 + -37 & -36.06 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -39 & -39.78 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -41 & -41.31 & 0.00 & [email protected] & 0.00 & [email protected] & 1 + -45 & -44.50 & 0.15 & [email protected] & 0.17 & [email protected] & 2 + -47 & -46.22 & 0.11 & [email protected] & 0.24 & [email protected] & 2 + [ tbl : southbin ] very few compact discrete cloud features have ever been observed in the near - equatorial region ( within about 10of the equator ) . most of the zonal drift rates in this region have been estimated by tracking wave features , either the ribbon wave that can be seen near 5s in the most of the high s / n images , or diffuse bright features that also seem to be associated with waves . an unusual appearance of compact discrete cloud features in the 2014 images in the 0 - 5s region provided a distinctly different drift rate estimate that is close to zero . which of these is the best estimate of the atmospheric mass flow is not certain , although waves are often seen traveling relative to the mass flow . thus we tend to favor the small discrete clouds as more representative of the mass flow . on the other hand , the only independent measure of the mass flow , inferred from radio occultation measurements @xcite suggests that the mass flow is more eastward than either the wave or discrete feature results , although the measurement has such a large error bar that it does not provide a very firm constraint . our aim in carrying out polynomial fits to the wind observations was to provide a smooth profile for atmospheric modelers and other researchers . we modeled longitudinal drift rates and wind speeds using the following legendre expansion and conversion equations:@xmath16 where @xmath17 are the coefficients given in table [ tbl : legfits ] , @xmath18 is the @xmath11th legendre polynomial evaluated at the sine of planetographic latitude @xmath19 , @xmath20 is the longitudinal drift rate in /h ( using planetographic longitude , which is east longitude for a retrograde rotator like uranus ) , @xmath21 is the westward wind speed in m / s , @xmath22 is the radius of rotation in km at latitude @xmath19 , which is the distance from a point on the 1-bar surface to the planet s rotational axis , and @xmath23 and @xmath24 are the equatorial and polar radii of uranus , for which we use 25559 km and 24973 km @xcite . we fit the longitudinal drift rates rather than wind speeds , because the former do not change as dramatically at high latitudes as the latter , and thus are much easier to fit without generating large deviations in data - sparse latitude regions . to limit such large deviations , we also need to limit the order of the polynomials . for the symmetric fits , the summation over @xmath11 is only over the even polynomials . the model coefficients are found by minimizing @xmath25 , but with error estimates for the observations modified as described by @xcite and paraphrased in the following paragraph . note that while we tabulate drift rates in east longitude , the plots show westward drift rates to be consistent with the prior practice of making prograde ( in this case westward ) winds positive @xcite . because very accurate measurements of drift rates at nearly the same latitude often differ by many times the value expected from those uncertainties , it appears that one or more of the following must be true : ( 1 ) the circulation is not entirely steady , ( 2 ) the features that we measure do not all represent the same atmospheric level , ( 3 ) the feature tracked has evolved or been misidentified , or ( 4 ) the cloud features we track are not always at the same latitude as the cloud - generating circulation feature that is moving with the zonal flow . examples of the latter possibility are the companion clouds to neptune s great dark spot @xcite . in section [ sec : ab ] we provide examples from our current data set . if we weighted highly accurate measurements by their expected inverse variance , they would dominate the fit , leading to wild variations in regions where there are less accurate measurements . since these high accuracy measurements clearly do not all follow the mean flow , we must add an additional uncertainty to characterize their deviations from it . we do this by root sum squaring the estimated error of measurement with an additional error of representation denoted by @xmath26 , which is adjusted so that the @xmath25 value of the complete fit is approximately equal to the number of measurements . the need for @xmath26 might be partly due to slight discrepancies in latitude that arise from a cloud feature being generated by a circulation feature that is latitudinally offset from the bright cloud feature that is tracked . another factor in evaluating wind measurement accuracy is the rate at which latitudinal accuracy and drift rate accuracy improve with extended tracking time spans . drift rate accuracy improves roughly linearly with time span , and can improve dramatically from just a few widely separated measurements , while latitude accuracy improves as the square root of the number of measurements , and is not much improved by adding just a few measurements or by extending the time span of the measurements . if we consider a shear of 2/h per 10of latitude ( about the maximum observed shear ) , a half - degree error in latitude is equivalent to a 0.1/h error in wind measurement , which is about the value of @xmath26 that we need to make the value for the fit equal to the number of degrees of freedom ( or /n@xmath27 @xmath4 1 ) . the apparent local stair steps suggested by the binned wind profile would also cause local errors relative to a smooth profile . we found @xmath28 0.1/h for both the 2009 - 2011 and 2007 - 2011 data sets analyzed by @xcite . a similar value was needed in our current analysis . because our 2012 - 2014 wind data set contains such a sparse sampling of the southern hemisphere , with no samples poleward of 47s , it is difficult to reliably constrain any north - south asymmetry in the wind profile . accordingly , we first considered fits using a series of even legendre polynomials , which guarantees hemispheric symmetry and provides a useful reference for detecting asymmetries . to fit the relatively sharp kinks near 55n and 62n , we needed to use a fairly large number of polynomials . after finding fit problems with orders of 10 - 14 , we settled on a ten - term series of even polynomials up to order 18 . the results are shown in fig . [ fig : symfitall ] for the case in which we fit essentially the entire data set , including 846 measurements and eliminating only 6 . this is shown as a solid line , while the most recent fit to prior observations , model s13a , is shown as a dotted line . here we also added synthetic points at both north and south poles to help straighten out our drift rate fit at high northern polar latitudes . we used a @xmath29 value of 0.147/h . the legendre coefficients and their uncertainties are given in table [ tbl : legfits ] . there we also provide coefficients for alternate fits discussed later in this section . in comparison with our new symmetric fit , the prior asymmetric fit provides a degree of asymmetry in the 20- 40range that seems to provide slightly better agreement with the new observations in that region . but in the region from 55n to 85n , the old fit has a solid body rotation rate that is 0.2/h too fast . this might represent a slight decrease over time , but the small number of 2011 measurements and their error bars of 0.3/h or more , make this a difference of dubious significance . near the equator , our new fit has a lower eastward drift rate , which is a result of the large number of high quality 2014 measurements between -6and 1that pull the profile closer to zero . our new fit is not quite straight enough to fit the constant rotation rate observed at high northern latitudes , but is within about 0.1/h of the correct drift rate . near the equator , this fit splits the difference between small discrete results and the large pattern results . this leads to a nearly solid body rotation within about 7.5of the equator , at a rate of about 0.12/h eastward . an alternative fit that eliminates the high - correlation low - latitude 2014 observations ( those associated with small discrete features ) , but leaving the drift rates derived from wave features , is shown in fig . [ fig : dualsymfits]a . for this fit we reduced @xmath29 to 0.128/h . this fit displays a clear retrograde ( eastward ) equatorial peak . realizing that the observations near 6s and near 2n , with drift rates less than -0.3/h are measurements of wave motions , while the 2014 measurements in this region are almost entirely of small discrete features that are more likely indicators of mass flow , we also carried out a fit in which the putative wave tracking results are eliminated . that fit , displayed in fig . [ fig : dualsymfits]b , contains a region within 15of the equator that appears to be in solid body rotation at a rate of 0.1/h eastward . c c c c c c c c + & legendre & & & + term & order & coeff . & unc . & coeff . & unc . & coeff . & + + 0 & 0 & -1.245225 & 0.0079 & -1.220885 & 0.0074 & -1.285259 & 0.0076 + 1 & 2 & -3.582487 & 0.0162 & -3.639650 & 0.0154 & -3.484602 & 0.0158 + 2 & 4 & -0.118185 & 0.0194 & -0.038439 & 0.0186 & -0.229385 & 0.0188 + 3 & 6 & 0.848593 & 0.0221 & 0.761227 & 0.0211 & 0.959671 & 0.0209 + 4 & 8 & 0.315199 & 0.0235 & 0.414609 & 0.0226 & 0.225287 & 0.0217 + 5 & 10 & -0.188857 & 0.0283 & -0.284082 & 0.0266 & -0.121381 & 0.0256 + 6 & 12 & -0.263077 & 0.0359 & -0.167412 & 0.0335 & -0.296423 & 0.0325 + 7 & 14 & -0.026728 & 0.0371 & -0.115626 & 0.0347 & -0.023522 & 0.0339 + 8 & 16 & 0.104192 & 0.0432 & 0.185315 & 0.0405 & 0.125384 & 0.0399 + 9 & 18 & 0.059944 & 0.0362 & 0.007696 & 0.0335 & 0.033149 & 0.0331 + [ tbl : legfits ] the very small asymmetry we see in the 2012 - 2014 observations is interesting to compare with prior observations of uranus . as shown in fig . [ fig : priorwinds ] , the strongest indication of mid - latitude asymmetry comes from observations made between 1997 and 2005 , which are based on hst imaging @xcite and keck imaging @xcite . the dotted curve in this figure is the sum of our symmetric fit and the all - data asymmetric fit to the differences from the symmetric fit , described later in the section and shown in the left panel of fig . [ fig : winddiff ] . observations from 2007 keck imaging @xcite and 2009 hst imaging @xcite are in close agreement with 2012 - 2014 results . the 2011 results @xcite from keck and gemini imaging , provide insufficient mid - latitude sampling to constrain the asymmetry properties of the circulation on their own , but they do contribute to the impression that there is indeed an asymmetry . this is made more apparent by the plots of measurements relative to the symmetric model in fig . [ fig : winddiff ] . there we also plot a simple model that provides a crude fit to the residuals . we considered two empirical models of the asymmetry . to fit the asymmetry average for all the high - quality observations from voyager through 2014 , we used the following model : @xmath30 where we found @xmath31=0.085/h to be the best - fit amplitude , @xmath32=29to be the best - fit peak location in latitude , and @xmath33=10.5to be the best - fit latitudinal width parameter . the second factor in eq . [ eq : asymm1 ] provides the sign reversal between hemispheres and is replaced by zero at the equator . a comparison of our fit to the observations can be found in fig . [ fig : winddiff ] ( left panel ) . measurements prior to 2012 - 2014 suggest a larger and more complex asymmetry structure , which we fit using the following model : @xmath34\exp(-((\theta - b)/c)^2 ) \label{eq : asymm2}\end{aligned}\ ] ] where in this case @xmath31=0.135/h provides the best - fit asymmetry amplitude , @xmath35=40.5provides the best latitudinal period of variation , @xmath32= 35the best peak of the exponential factor , and @xmath33=19.5the best damping width of the exponential . these parameters are only crudely constrained by the observations , as can be seen from a comparison of this model with the difference plots in fig . [ fig : winddiff ] ( right panel ) . voyager approached uranus in 1986 , when the southern hemisphere was facing the sun , but very few winds were obtained because very few cloud features were detected . recently , @xcite carried out an extensive reprocessing of voyager imagery to remove artifacts , improve non - linearity corrections , and carry out shift - and - add averaging , similar to the high s / n approach we used in our analysis , except that many more images were averaged and much higher s / n ratios were achieved , allowing the detection of very low contrast cloud patterns and discrete cloud features over most of the southern hemisphere . twenty - seven discrete cloud features were tracked between 87s and 23.6s . these are shown in fig . [ fig : southcomp ] in comparison to the asymmetric profile of @xcite and to southern hemisphere measurements from our 2012 - 2014 data set . also shown is the result of karkoschka s correlation tracking at 395 latitudes between the equator and the pole . these new results are in generally good agreement with current and prior results north of 55s , where the non - voyager results exist . but there are many substantial deviations and remarkable asymmetries implied by the new results , as discussed in the following paragraphs . first , we consider the correlation tracking results ( small black dots in fig . [ fig : southcomp ] ) . these show regions of constant longitudinal drift rate , or solid - body rotation ( 26s - 36s , 36s - 42s , and 58s - 68s , for example ) . the regions north of 50s are not in agreement with prior measurements , as shown in fig . [ fig : corrcomp ] , most of which follow a smooth variation with latitude . exceptions are probably due to the fact that larger vortex features can generate cloud features over a range of latitudes that travel along with the generating feature rather than following the zonal wind profile . major examples of this effect are provided by the great dark spot and other dark spots on neptune @xcite . we also identify a pair of uranian features with this characteristic in section [ sec : ab ] . thus , it is conceivable that , at least where we have contradicting observations , the regions where karkoschka s voyager correlation results show solid - body rotation are due to large circulation features that influence an extended latitude region , generating clouds that travel with the circulation features rather than following the zonal flow . this is less plausible as an explanation for the 58s to 68s region because of its size . while we find small regions of apparent solid body rotation in our data set in the northern hemisphere , these are not as extensive as the mid - latitude regions in karkoschka s correlation profile . the major region of solid body rotation that we find , from 62n to 83n , is clearly not an artifact , as it is based on numerous well - defined discrete cloud features . there is an amazing amount of shear in karkoschka s correlation profile , just where one solid body region transitions to another . when plotted as wind speeds , there regions of enormous jumps in wind speed over a very short distance , zig - zagging to higher values as latitude increases toward the pole , then decreasing for a while , then jumping again to a new high . this characteristic also suggests that these features might not represent the zonal wind structure . the most extraordinary result from @xcite is the huge north - south asymmetry it implies at high latitudes . between 70s and 87s , his inferred westward drift rates rises from 3.8/h to 8.6/h , which is more than double what we measured at high northern latitudes , where drift rates are invariant with latitude over a comparable latitude range . given that the middle latitude winds have changed by barely measurable amounts from 1986 through 2014 , a 28-year period , it is hard to understand how such enormous seasonal changes might occur . if the north - south difference is seasonal , and the voyager analysis represents the winds at the southern summer solstice ( october 6 , 1985 ) , then we would expect that the same wind profile would appear in northern latitudes by the time of the northern summer solstice in 2030 ( on april 29 according to @xcite ) . that is less than 16 years over which this enormous change should occur , while almost nothing has changed at middle latitudes in the last 28 years . evidence for change at high latitudes is only beginning to be accumulated . there may have been a small decrease in the solid body rotation rate from 4.3/h to 4.1/h between 2011 and 2014 , but that is probably within the error of the 2011 measurements , and provides little evidence for the rapid change needed to match in 2030 what seems to have existed in 1986 in the southern hemisphere , according to @xcite . on the other hand , perhaps this north - south difference is a permanent feature of the wind profile , just as it appears that jupiter and saturn have asymmetries that survive over a complete change of seasons . it will certainly be worthwhile to monitor the winds of uranus over the next two decades to determine whether this asymmetry is really a seasonal effect . here we create a complete pole - to - pole zonal wind profile for uranus by combining results from groundbased observations at latitudes spanning 47s to 83n with the recent @xcite results for the southern hemisphere , obtained from 1986 voyager 2 imaging . in fig . [ fig : compositewinds ] we show our composite profile in comparison with binned observations and the discrete cloud tracking results of @xcite . the composite profile uses our symmetric fit to our 2012 - 2014 observations ( fig . [ fig : symfitall ] ) summed with the asymmetric fit to differences from that profile , as displayed in fig . [ fig : winddiff]a , to cover the latitude range from 46s to 67n . from 67n to 90n we used a solid - body rotation profile of 4.1/h westward . from 47s to 90s we used the adopted profile of @xcite . the latter profile does not pass exactly through the discrete measurements in this region , probably because the profile also took into account correlation measurements . the composite profile is also provided in tables [ tbl : adoptdrate ] and [ tbl : adoptwind ] . this represents our best estimate of the zonal wind profile of uranus under the assumption that the indicated asymmetry is a permanent feature of the atmosphere . this may be an incorrect assumption . since the southern winds from voyager are based on 1986 observations , while the remaining winds ( from 47s to 90n ) are based on observations heavily weighted towards the 2012 - 2014 time period , this may not represent the current profile . r r r r r r r r r r r l , & d(l)&d(l-1)&d(l-2)&d(l-3)&d(l-4)&d(l-5)&d(l-6)&d(l-7)&d(l-8)&d(l-9 ) + + 90 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 + 80 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 & 4.100 + 70 & 4.100 & 4.100 & 4.100 & 4.100 & 4.097 & 4.100 & 4.099 & 4.090 & 4.072 & 4.043 + 60 & 4.002 & 3.946 & 3.875 & 3.789 & 3.687 & 3.571 & 3.443 & 3.302 & 3.153 & 2.997 + 50 & 2.836 & 2.673 & 2.510 & 2.349 & 2.191 & 2.039 & 1.893 & 1.753 & 1.620 & 1.493 + 40 & 1.373 & 1.258 & 1.149 & 1.045 & 0.946 & 0.850 & 0.759 & 0.672 & 0.588 & 0.509 + 30 & 0.434 & 0.363 & 0.298 & 0.237 & 0.181 & 0.129 & 0.083 & 0.040 & 0.002 & -0.032 + 20 & -0.064 & -0.092 & -0.118 & -0.142 & -0.164 & -0.185 & -0.204 & -0.222 & -0.238 & -0.253 + 10 & -0.266 & -0.278 & -0.289 & -0.298 & -0.305 & -0.312 & -0.317 & -0.321 & -0.323 & -0.325 + 0 & -0.325 & -0.324 & -0.322 & -0.319 & -0.314 & -0.308 & -0.300 & -0.290 & -0.278 & -0.264 + -10 & -0.247 & -0.228 & -0.206 & -0.181 & -0.154 & -0.124 & -0.090 & -0.054 & -0.015 & 0.027 + -20 & 0.072 & 0.120 & 0.170 & 0.223 & 0.278 & 0.335 & 0.394 & 0.455 & 0.518 & 0.582 + -30 & 0.647 & 0.714 & 0.783 & 0.854 & 0.927 & 1.002 & 1.081 & 1.164 & 1.253 & 1.346 + -40 & 1.447 & 1.554 & 1.669 & 1.793 & 1.924 & 2.064 & 2.210 & 2.359 & 2.501 & 2.645 + -50 & 2.790 & 2.937 & 3.086 & 3.166 & 3.247 & 3.328 & 3.410 & 3.492 & 3.575 & 3.578 + -60 & 3.581 & 3.585 & 3.588 & 3.591 & 3.595 & 3.598 & 3.601 & 3.605 & 3.608 & 3.749 + -70 & 3.891 & 4.035 & 4.181 & 4.328 & 4.596 & 4.869 & 5.120 & 5.377 & 5.638 & 5.904 + -80 & 6.250 & 6.605 & 6.970 & 7.344 & 7.729 & 8.124 & 8.530 & 8.530 & 8.530 & 8.530 + -90 & 8.530 & & & & & & & & & + [ tbl : adoptdrate ] r r r r r r r r r r r l , & u(l)&u(l-1)&u(l-2)&u(l-3)&u(l-4)&u(l-5)&u(l-6)&u(l-7)&u(l-8)&u(l-9 ) + + 90 & 0.00 & 9.07 & 18.15 & 27.21 & 36.27 & 45.31 & 54.34 & 63.35 & 72.33 & 81.29 + 80 & 90.23 & 99.13 & 108.00 & 116.83 & 125.62 & 134.36 & 143.06 & 151.72 & 160.32 & 168.86 + 70 & 177.35 & 185.77 & 194.14 & 202.43 & 210.53 & 218.84 & 226.82 & 234.33 & 241.20 & 247.23 + 60 & 252.26 & 256.13 & 258.70 & 259.87 & 259.57 & 257.78 & 254.54 & 249.90 & 243.99 & 236.94 + 50 & 228.93 & 220.13 & 210.74 & 200.94 & 190.88 & 180.72 & 170.58 & 160.54 & 150.67 & 140.99 + 40 & 131.53 & 122.27 & 113.20 & 104.30 & 95.56 & 86.97 & 78.54 & 70.28 & 62.22 & 54.39 + 30 & 46.83 & 39.60 & 32.73 & 26.26 & 20.20 & 14.58 & 9.40 & 4.63 & 0.26 & -3.75 + 20 & -7.43 & -10.82 & -13.96 & -16.88 & -19.60 & -22.16 & -24.55 & -26.78 & -28.85 & -30.75 + 10 & -32.49 & -34.05 & -35.43 & -36.63 & -37.64 & -38.49 & -39.16 & -39.67 & -40.02 & -40.22 + 0 & -40.24 & -40.11 & -39.85 & -39.42 & -38.81 & -37.99 & -36.95 & -35.66 & -34.12 & -32.29 + -10 & -30.17 & -27.74 & -24.99 & -21.92 & -18.53 & -14.81 & -10.77 & -6.41 & -1.76 & 3.19 + -20 & 8.41 & 13.87 & 19.57 & 25.47 & 31.55 & 37.76 & 44.08 & 50.48 & 56.92 & 63.39 + -30 & 69.87 & 76.35 & 82.83 & 89.33 & 95.88 & 102.50 & 109.26 & 116.20 & 123.37 & 130.83 + -40 & 138.62 & 146.78 & 155.32 & 164.22 & 173.44 & 182.92 & 192.53 & 201.83 & 210.02 & 217.83 + -50 & 225.25 & 232.26 & 238.84 & 239.62 & 240.08 & 240.23 & 240.04 & 239.52 & 238.66 & 232.26 + -60 & 225.77 & 219.19 & 212.53 & 205.78 & 198.95 & 192.04 & 185.05 & 177.98 & 170.85 & 169.86 + -70 & 168.32 & 166.19 & 163.48 & 160.17 & 160.37 & 159.58 & 156.88 & 153.20 & 148.50 & 142.75 + -80 & 137.54 & 130.97 & 122.96 & 113.47 & 102.43 & 89.78 & 75.45 & 56.61 & 37.75 & 18.88 + -90 & 0.000 & & & & & & & & & + [ tbl : adoptwind ] a number of discrete features and cloud patterns were found to persist for long time periods . to facilitate their identification we created a mosaic of high s / n h - filter images for each high - resolution data set for which successive observing nights allowed us to take multiple images of both sides of the planet , totaling between 144 and 179 images per data set . this made it possible to combine all longitudes into one rectangular map . overlapping images were blended with a weighting of @xmath36 , where @xmath37 is the observer zenith angle cosine and @xmath38 is the image exposure ratio . also , pixels were mosaicked only if @xmath37 and @xmath39 ( solar incidence angle cosine ) were greater than or equal to 0.025 . these two cosines are so close together that a minnaert model of brightness variation , i.e. @xmath40 , which is fit well with @xmath41 for h - filter images , collapses to @xmath42 . because this is a such a weak dependence on view angle we did not attempt to correct for it . high - pass filtered versions of these mosaics are shown as rectangular projections in fig . [ fig : rectpro ] at a scale 0.25/pixel . these were obtained by subtracting from the mosaicked images a version smoothed with a 6.25(25-pixel ) boxcar average . to display the resulting low - contrast variations , we enhanced these images so that black and white respectively correspond to i / f deviations of -0.4@xmath43 and + 0.8@xmath43 from the smoothed versions , which have a central disk i / f of about 0.01 . the combination of images taken at different times requires that each longitudinal image line from each component image be shifted by the zonal wind drift rate times the time difference between the image time and the reference time of the map ( chosen to be the midpoint of the observations for the two nights ) . this does not distort features at low and high latitudes , because wind shear is very low at low latitudes and zero above 55n . however , at middle latitudes ( 25 - 55 ) , where wind shear is significant , round features become stretched into slanted ellipses . this distortion is a reasonable price to pay for obtaining a global view of where features are located and how many features are present in a given band of latitude . for key features that are identified , we also provide in the following section undistorted views that more accurately display morphological characteristics . + inspecting the four rectangular maps in fig . [ fig : rectpro ] , we see that there are too many features of similar appearance in the north polar region to identify which , if any , might have lasted for long time periods . the band from 45n to 50n also has too many features to make any unambiguous matches between data sets . in other , less populated regions , we were able to identify six discrete long - lived features ( a - f ) , which are also shown enlarged and without high - pass filtering in fig . [ fig : featuresabcdfg ] . between 20n and 30n , only two significant features are seen in july 2012 ( a1 and b1 ) , november 2012 ( a2 and b2 ) , and august 2013 ( a3 and b3 ) . a1 and a2 have nearly identical morphologies and latitudes ( @xmath425n ) , making identification rather easy . in the high - pass filtered images they appear as small dark spots with what look like companion clouds traveling with them , consistent with the idea that the bright features are orographic clouds generated by vertical deflections associated with flow around an oval vortex . in this case vertical deflections cause adiabatic cooling and condensation of cloud particles . the dark feature so clearly visible in the high - pass filtered version is also apparent without such filtering , as shown in fig . [ fig : featuresabcdfg ] . feature a3 is likely associated with the same vortex , but the morphological match is not as good , with no dark spot showing . feature b is at essentially the same latitude as feature a , but its bright features can be found both north and south of the bright features associated with a. from a comparison of a2 and b2 subimages in fig . [ fig : featuresabcdfg ] , we see that the bright features of b are indeed north of the bright features of a , but there seems to be a dark spot associated with b that is at a lower latitude than the dark spot associated with a. it is likely that the latitude of the dark spot is what really matters because the bright features are likely to follow the motion of the dark spot , rather than the zonal wind profile , a behavior already well established for dark spots on neptune . one feature that seems to have survived at the same latitude all the way from july 2012 to august 2014 , is the feature labeled c1-c4 , which appears at latitude 38n . to solidify the identification of discrete features , we tried to add longitudinal continuity to the morphological character and zonal uniqueness evident at several discrete times . if the features we have identified as unique are indeed the same at each time period , then their longitudes should be a continuous function of time that is roughly consistent with the zonal winds within the latitude region where they are found . during 2012 we acquired observations over a 4-month period , with a similar range covered in 2014 , providing strong constraints on longitudinal and latitudinal motions , but only one sample was obtained between these times , during 15 - 16 august 2013 . we first tried to fit observations to the simplest model in which longitude is a linear function of time , implying that the drift rate is constant and that the latitude of the feature ( or that of the circulation feature generating the visible cloud feature ) is constant . none of the long - lived features followed this simple model for the entire time period . two other models were then considered : ( 1 ) a sinusoidal variation in drift rate ( and latitude ) , which leads to a sinusoidal variation in longitude relative to a linearly increasing longitude , and ( 2 ) a linear variation in drift rate ( and a linearly increasing latitude ) , which implies that the longitude should vary as the square of the time difference ( at least over small ranges of latitude for which a constant wind shear is a plausible assumption ) . the linear latitudinal drift model can be expressed as follows : @xmath44 where @xmath45 is longitude at time @xmath46 , @xmath47 is rate of change of longitude , @xmath19 is latitude , and @xmath48 is the latitudinal shear in the zonal wind profile . the corresponding equations for the sinusoidal variation model are as follows : @xmath49 where @xmath50 is the period of variation . when the period becomes significantly longer than the span of the observations , it becomes difficult to distinguish the two models . for one feature ( d ) , we needed to include both types of variations : @xmath51 where we also introduced a new time offset @xmath52 . as a result of the additional time offset , this model has @xmath53 and @xmath54 , while for all the other models , @xmath55 and @xmath56 . in all cases @xmath57 is determined by solving for @xmath58 , where @xmath59 is the measured zonal wind profile . all the adjustable constants are constrained by fits to the longitude measurements . our best - fit models are summarized in table [ tbl : longtrack ] and discussed in the following paragraphs . c c c c c c c c c + & @xmath60 & @xmath57 & @xmath61 & @xmath35 & @xmath32 & @xmath33 & @xmath50 & @xmath62 + i d & days & n & e & /d ( east ) & 0.001/d@xmath63 & & days & + + a & [email protected] & 27.6 & 120.0 & [email protected] & [email protected] & & & 1.7 + b & [email protected] & 22.4 & 5.0 & [email protected] & & [email protected] & 686@xmath210 & 1.4 + c & 148.5@xmath20 & 38.6 & 271.0 & [email protected] & & [email protected] & [email protected] & 2.9 + d & [email protected] & -33.2 & [email protected] & [email protected] & [email protected] & 35.0 & 750.0 & 1.9 + e & [email protected] & -41.7 & 20.0 & [email protected] & [email protected] & & & 6.5 + f & [email protected] & 34.1 & 125.0 & [email protected] & & [email protected] & [email protected] & 1.6 + + [ tbl : longtrack ] these low - latitude features were seen during 2012 and 2013 , but not in the unusual 2014 images , where an abundance of low latitude features developed , none of which seen to have any relationship to a and b. both a and b seem to involve a dark spot , as suggested in fig . [ fig : featuresabcdfg ] , and both moved toward the equator between 2012 and 2013 , though it is not clear if that trend continued after august 2013 . their rate of equatorward drift was about 2/year . an equatorial drift ( accelerating from 2/y to more than 10/y ) was also observed for the large southern uranian feature named the berg @xcite , and for the great dark spot on neptune , which averaged 15/y @xcite . the drift of these new uranian features suggests that they might also be produced by vortex circulations . it is possible to fit feature a longitude observations extremely well with the sinusoidal model using a period of 408.2 days , but this model does not reproduce the decreasing latitude from 2012 through 2013 . the alternative increasing drift rate model ( fig . [ fig : atrack ] ) provides an excellent fit to longitude measurements and also is consistent with the rate of equatorward motion of the feature from 2012 to 2013 . however , the model latitude that is inferred from the feature s longitudinal drift rate , is about 2n of the observed latitude of the bright features , suggesting that the underlying circulation feature is to the north of the bright clouds that it generates , which is also suggested by the images for a1 and a2 in fig . [ fig : featuresabcdfg ] . feature b had a nearly linear drift rate of -0.060/h during 2012 , and a drift rate of + 0.0259/h during 2013 . this can be joined and well fit with a sinusoidal model , using an average drift rate of -0.0176/h ( -0.442/day ) , an oscillation amplitude of 118 , a period of 686 days ( shown in fig . [ fig : btrack ] ) . this model is also consistent with the observed latitudinal drift over that time period ( see panel b ) , but the model latitude is about 2s of the observed latitude , an offset opposite to that observed for a , but consistent with what is shown in image b2 of fig . [ fig : featuresabcdfg ] . a feature seen in 2006 and either the same or another feature seen in 2007 @xcite appeared at about 27n , close to the latitude observed for features a and b. these earlier features also seemed to be associated with dark spots , and the 2006 feature was seen as a dark spot in an hst acs image at 658 nm @xcite . these might be related to either a or b in our current data set , based on similarity in morphology as well as latitude . feature c , located at about 36.5n , is the longest living feature we observed , appearing in august and november 2012 data sets , as well as in 2013 and 2014 data sets , including august as well as november 2014 images . it is also a feature that does not seem to have drifted in latitude over this time period , although its varying drift rate suggests a small oscillation in latitude of less than 1 in amplitude . feature c can also be roughly fit with model that includes a sinusoidal variation about a mean drift rate , with a much greater average drift rate of -1.2157/h , compared to a or b , a much shorter period of variation ( 258 days ) compared to b , and a much smaller amplitude of 27.5(see fig . [ fig : ctrack ] ) , which leads to a much smaller latitudinal variation ( panel c ) than feature b. however , the latitudinal measurements of c exhibit considerable scatter , especially in the latter 2014 observations , although for most of the range the observed and model latitudes are within 1 - 2 degrees , with the model being north of the measurements . a possible reason for the poorer fit of feature c in comparison with features a and b is that c is near a latitude region containing many features that might perturb its motions , as well as being in a region of relatively high zonal wind shear , so that slight latitude shifts might yield significant changes in drift rate . the southern hemisphere features d and e both were observed to move towards the equator during the two years spanned by our observations . and both appear to have existed for the entire time period , but are harder to observe because at their latitudes we can only see a small range of longitudes in any given image , a consequence of the sub - observer point being in the northern hemisphere . feature d is relatively compact and is not difficult to measure when it can be seen . the longitude of feature e is particularly difficult to measure accurately because of the feature s long narrow morphology . our model fit to d is displayed in fig . [ fig : dtrack ] . as it moves from about 35s to about 32s , its drift rate is seen to increase from -0.87/h to -0.7/h . the drift rate model , when converted to a latitudinal variation using model s13a to relate drift rate to latitude , yields a latitudinal slope in good agreement with observations , and also agrees well with the absolute value of the latitude . a more accurate fit to the measured longitudes can be obtained with a baseline drift of -0.7145/h , with drift rate varying from -0.73/h to -0.52/h , which reduces the rms deviation from 14.1to 9.0 , but the inferred latitude then becomes about 3greater than the observed latitude . this might be a consequence of the cloud features being displaced in latitude from the circulation feature that is actually following the zonal mass flow . both fits can be substantially improved by adding another component of variation , namely a sinusoidal deviation from the quadratic model , as shown by the dashed line in fig . [ fig : dtrack ] , which reduces the rms deviation down to 1.9for the model that agrees well with the observed latitudes . that variation has a period of 750 days and an amplitude of 35 in longitude . an even longer period of nearly three years was observed for a prior southern hemisphere long - lived feature named the berg @xcite . that feature spent most of its time oscillating @xmath22about a mean latitude of 35.2s ( planetographic ) , then in 2005 began to drift towards the equator , reaching 27s by 2007 and reaching 5s and dissipating in late 2009 @xcite . feature e ( model fit in fig . 23 ) was first seen near 41s and last seen near 38s . its latitude seems to follow a linear trend of about 1/year towards the equator , and the longitudinal model fit is compatible with latitudinal variation obtained by interpolation of model s13a of @xcite . however , there are so few observations of this feature that we can not entirely rule out other drift rate models . all the features in the 2012 - 2014 data sets that were observed to have substantial latitudinal motions moved towards the equator , as did the previously mentioned berg feature last seen in 2009 . found near 34n planetographic latitude ( figs . [ fig : rectpro ] and [ fig : featuresabcdfg ] ) , feature f , which is feature 2 of @xcite , is the first discrete cloud feature ever clearly detected by amateurs using ccd detectors and small telescopes @xcite . compared to most other prominent northern - hemisphere features seen in 2014 , feature f was not particularly bright at near - ir wavelengths and did not extend to as high an altitude . it was not seen in k@xmath3 images , placing it deeper than the 1-bar level according to fig . [ fig : penprof ] , while several other 2014 features were spectacularly bright at that wavelength , with g being the most notable @xcite . yet , it was f that was detected by amateurs , probably because it had a substantially greater optical depth than surrounding clouds . feature f turned out to have an exceptionally long life and was tracked by amateurs as well as by hst observations using a too program 13712 ( k. sayanagi , pi ) and opal program 13937 ( a. simon , pi ) , and by observations from gemini , keck , and palomar , which are all summarized by @xcite . our model fit to its motions is displayed in fig . we first saw f in our 2014 keck images , but were not able to identify it in 2013 or 2012 images . this is not because of confusion about which feature is which . when we project our model backward we find no feature at all anywhere near the predicted location . thus it appears that f developed sometime between august 2013 and august 2014 . f also has an unusual morphology . it appears to have a very short plume extending to the west on its north side and a very extensive plume extending eastward over more than 100of longitude on its south side ( see figs . [ fig : rectpro ] and [ fig : featuresabcdfg ] ) . the direction of the plume is consistent with cloud particles spreading out from f mainly to the south , then following the zonal flow and falling behind the faster ( more westward ) motion of f. given the f - to - plume latitude distance of 3 - 4and the local wind shear of 0.084/h per degree of latitude ( from table [ tbl : adoptdrate ] ) . the time to extend the plume 100of longitude would be 30 to 40 hours . of course the length of the plume is also limited by particle fallout , so the time span of convective activity and plume generation could of course have been much longer . the prominence of the f plume is a marker of its unusual convective strength relative to other features in similar shear regions that generate no plumes and is consistent with a large optical depth that would facilitate amateur detection of the feature . the last observation of this feature at the time of this writing was obtained on 8 january 2015 , using the gemini niri imager . at that time it did not appear to have a prominent plume , suggesting that its convective activity has substantially declined . it was found just 12east of the location predicted using the model in table 8 . long - lived features at nearby latitudes move at different longitudinal speeds and will eventually approach each other at close range , raising the possibility of some sort of interaction . an example of this occurred on 25 december 2011 , when two bright features separated by 2 in latitude had a close approach that resulted in formation of a small dark spot and companion clouds @xcite . a close approach observed on saturn @xcite resulted in a more dramatic development of bright clouds during the interaction . it is also possible that features might merge or dissipate . examples of dark spots merging on saturn can be found in fig . 3 of @xcite . if the features have underlying vortex circulations of similar vorticities , we might expect to see latitudinal deflections in opposite directions as they pass by each other , followed by a return to their original latitudes . it is less clear what changes to expect in the structure of their companion clouds . we found no evidence of strong interactions for the two feature pairs described below . long - term tracking of a and b features show that b has an average drift rate of [email protected]/h , while a has an average drift rate of [email protected]/h , with this average taken over a period from late august 2012 to 4 - 5 november 2012 . given that the winds become more westward at higher latitudes , the drift rate comparison suggests that the putative vortex generating the a features is actually north of the vortex generating the b features . this is consistent with the november 4 - 5 appearance of the features in fig . [ fig : featuresabcdfg ] . the long term tracking of these two features , illustrated in fig . [ fig : abtrack ] , provides another surprising result . since their sizes ( judged by the extent of the bright clouds associated with them ) are somewhat greater than the latitudinal difference between them , we would expect some sort of interaction when they pass by each other . however , even though they reached the same longitude on september 7 , 2012 , their drift rates before and after that close encounter were not perceptibly changed . features a and b had three more close encounters before our next observing run on 15 - 16 august 2013 , yet they remained distinguishable features . however , there is considerable ambiguity as to what happened during the nearly 10 months without any observations . extending the drift track of these features to the august 2013 date , we find close approaches should have occurred on 5 december 2012 and 25 march 2013 . it is plausible that the multiple close approaches altered their latitudes and drift rates slightly , and our assumed model of a linear variation in latitude ( and in drift rate ) may not be correct . a non - uniformly varying drift rate has been observed for other long lived features on uranus , so this would not be surprising . it is also possible that one or both of the features disappeared during that unobserved period and that at least one of them in our 2013 images is a new feature . also noteworthy , is that the latitudes we infer from our drift rate models interpolated to latitudes using the zonal profile of @xcite , suggest that feature a is following a circulation feature that is about 2n of the observed bright clouds and that feature b is following a circulation feature this is about 3s of the bright clouds associated with it . in this connection it is worth noting that the rectangular projections of a2 and b2 in fig . [ fig : featuresabcdfg ] for november 2012 ( 2nd row from bottom ) provide evidence of a dark spot associated with a that is north of the bright clouds accompanying it , and a dark spot associated with b that is south of the bright clouds accompanying it . the inferred separation of about 5 in latitude makes it somewhat more plausible that the features seem to suffer no major interactions . and [ fig : btrack ] , the latter plotted with multiple 360offsets to show crossing events more clearly ( these are marked by vertical dashed lines and annotated by date at which they reach the same longitude ) . , width=336 ] close approaches of features c and f are shown by intersections of longitude versus time plots in fig . [ fig : cftrack ] . the average latitudes for features c and f are 36n and 34n respectively . since each of these appears to extend over several degrees of latitude ( see fig . [ fig : featuresabcdfg ] ) , it would be surprising if they did not display evidence of some interaction . in fact , these were observed in such close proximity in hst images acquired on 14 october 2014 ( taken as part of a target of opportunity program , with kunio sayanagi as pi ) , that we initially thought we were observing a single feature . we also observed them in close proximity in a gemini niri image acquired on 19 november , about 1 day after close approach . both of these close approaches are consistent with the longitude versus time plots shown in fig . [ fig : cftrack ] . besides the 14 october and 18 november approaches , we also found unobserved close approaches on 12 september 2014 and 20 december 2014 . there is no evidence of any change in drift rate or , based on a 26 november gemini image , any change in the morphology of the features following these possible interactions , although f was seen close to the central meridian only in the late november image . @xcite identified several bright features in the 2014 keck observations , one of exceptional brightness , which is labeled as g in fig . [ fig : rectpro ] . this appears to have faded dramatically within a month or so . a similarly bright cloud feature was detected in august 2005 @xcite , but at a higher latitude ( 31n ) . it brightened and faded dramatically within a few months , and extended to similarly high altitudes ( @xmath1300 mbar level ) . the 2007 equinox observations @xcite provided the first detection of cloud features north of the 60n westward jet peak . more features were seen in 2011 images , and it appeared that the north polar region was peppered with small low - contrast discrete clouds @xcite , presenting what looked like a field of fair - weather cumulus convection on earth , but on a much larger scale . this was not expected because such features had never been seen in the south polar region . from 2012 onward , the improved views of the north polar region of uranus have allowed us to combine observations from successive observing nights to form a complete picture of the polar region . because the entire region from about 63n to at least 83n moves in solid body rotation , we were able to average images with that rotation period removed to obtain a pole - centered high s / n view of uranus north polar region for each of the three years of observation ( fig . [ fig : poleviews ] ) . these show a continued prevalence of large numbers of small bright features . almost all the polar bright features have similar size and shape , which is mainly circular . typical diameters are 600 - 800 km , which is comparable to imaging resolution , and thus is an upper limit for the smaller features . there are also less numerous but well - defined small dark spots , many of which are well separated from bright spots and thus can not be explained as an artifact of high - pass filtering . the small bright features have a typical contrast of 1 - 2% in the raw images , with a much brighter than typical feature in the 4 - 5 november image reaching 10% . the dark features have only a fraction of the contrast of the bright features ( as well as the opposite sign ) . the lifetimes of the polar features can extend for at least 1.5 planet rotations , as quite a few of these have been tracked over that time period ( not continuously , but with a one- rotation gap ) . the large number of features seen in the november 2012 data set seems to indicate the clear peak in activity . at a casual glance these spots appear to be fairly uniformly distributed in latitude and longitude , down to a latitude of about 55n , where there begins a transition to a morphology dominated by longitudinally stretched streaky features often occurring within long narrow regions of enhanced brightness with a width comparable to the diameter of the small polar spots . however , there is a pattern in the distribution of features that has at least some crude year - to - year consistency , as discussed in section [ sec : polepat ] . + it is worth recalling , as demonstrated in fig . 1 of @xcite , that when the south polar region was imaged in 2003 , using the same telescope , camera , and essentially similar ao system , no discrete polar features of any kind were observed between 50s and the south pole . that observation was made in southern hemisphere fall , while the current observations were made during northern hemisphere spring . one might surmise that this seasonal difference is the cause of this striking morphological asymmetry . a long season of radiative cooling from the top of the atmosphere during uranus northern winter might tend to produce an unstable thermal profile that favors vertical mixing , which is likely to be most active following equinox . on the other hand , the long summer of heating from above during southern hemisphere summer might stabilize the thermal profile and inhibit vertical convection in southern polar regions in the fall . although this has a plausible ring to it , there are other indicators of vertical convection , such as depleted methane mixing ratios in both polar regions at the same time @xcite , which argues against such seasonal modulations in at least the large scale flow . we are expecting that this `` convective '' activity might continue for a while as the northern hemisphere moves into summer , but it is plausible to expect it to eventually dissipate as summer heating intensifies . we also expect the formation of a polar cap cloud @xcite , which appears to have begun @xcite . a closer look reveals that the zonal average relative brightness between 50n and 90n displays a roughly consistent pattern , evident in the zonally averaged polar projections in fig . [ fig : poleviews ] , and the plot of relative brightness versus latitude in fig . [ fig : zonalav ] . in the average for all three years , the two 2012 values are averaged together to represent the average for that year . all three years have minima near planetographic latitudes of 53 - 54n , 60 - 61n , 70 - 71n , and 76 - 80n , though the 2012 november 4 - 5 composite is somewhat of an anomaly , with both larger numbers of polar features and features of greater contrast than seen in other years . other details regarding positioning and widths and numbers of various bands vary from year to year . between 60n and 80n , the august 2012 and 2013 composites have better pattern agreement with each other than either has with the 2014 composite . but at 80n and 90n the 2013 and 2014 composites agree much better with each other than with the 2012 composites . whether these changes from year to year are real trends , or just due to stochastic variations is hard to evaluate without more observations . certainly 2012 demonstrates considerable variability within a single year . the 3-year average pattern is roughly consistent with observed high - latitude variations in the apparent methane mixing ratio inferred from 2012 stis observations by @xcite , who noted the correlation with 2012 keck observations . they also pointed out that these apparent mixing ratio variations might actually be caused by para fraction variations induced by local vertical convection . . the average over all data sets ( giving equal weights to each year ) is plotted as a thick dark gray curve , and a scaled and inverted version of the methane profile of @xcite is plotted in the lower part of the figure , where the variations between 60and 80correspond to ch@xmath64 volume mixing ratio variations of about @xmath20.005 relative to a mean of 0.02 . as noted by @xcite , these variation might actually be caused by para fraction variations induced by local vertical convection . , width=336 ] a more detailed view of polar cloud features is presented in fig . [ fig : spotdetail ] , where we see that almost all features have about the same size , which is 600 km to 800 km according to 2-d gaussian fits to many of the features . line scans through several bright and dark spots are plotted in the bottom panel of fig . [ fig : spotdetail ] , showing that both bright and dark features have fwhm values comparable to the keck nirc2 psf ( about 0.06@xmath5 ) . thus , these features are generally not resolved and might actually be considerably smaller than they appear in these images . the dark spots , which are possibly regions of reduced cloud opacity , perhaps produced by downwelling motions , have lower contrast than bright features , but are of similar apparent size . spacing between features is typically 1000 km to several thousand km . the dark spots are generally found at higher latitudes than the bright features , most within 20of the pole . there is also another change in distribution between regions close to the pole , where spots appear to be randomly distributed , and regions further from the pole , where features seem to appear more often as beads on a string , with the `` string '' in this case lying along a circle of constant latitude . in h under ideal conditions ) . in the upper panel , circles of constant distances from the pole provide a sense of the physical scale . the small square centered at the pole is 1000 km on a side . this image was also high - pass filtered as in fig . [ fig : poleviews ] . the contrast in unfiltered images was measured to be 2.7% for the brighter feature along scan b and 2% for the feature intersected by scan a.,title="fig:",width=336 ] in h under ideal conditions ) . in the upper panel , circles of constant distances from the pole provide a sense of the physical scale . the small square centered at the pole is 1000 km on a side . this image was also high - pass filtered as in fig . [ fig : poleviews ] . the contrast in unfiltered images was measured to be 2.7% for the brighter feature along scan b and 2% for the feature intersected by scan a.,title="fig:",width=336 ] one of the more striking features in uranus atmosphere is the scalloped wave form that was first brought to light by high - s / n measurements in 2012 . the immediate appearance is that of two sine waves that criss - cross each other , similar to a two strand braid ( fiq . [ fig : featuresekw ] ) . this appears strikingly similar to vertically varying cloud forms created by kelvin - helmholtz instabilities generated by sharp vertical gradients in the horizontal winds . a different wave mechanism must be at work here however , perhaps kelvin waves or mixed internal gravity - rossby waves . a correct identification would be helped by measuring its dispersion relation ( phase speed versus wavelength ) , which is not likely to be feasible with current observations . the lower boundary of this morphology is a sort of ribbon wave ( fiq . [ fig : wavefits ] ) , though the ribbon does not have a constant latitudinal width . the better defined upper boundary of the ribbon , which is the lower boundary of the scalloped features , is somewhat sinusoidal , with a longitudinal wavelength of about 20 ( corresponding to a wavenumber of 17 to 19 ) , with only a small decrease from 21 in 2012 to 19 in 2014 , and a latitudinal peak - to - peak amplitude of about 2.4 - 2.9 . the dark ribbon itself has a width of about 1 - 2 in latitude . the ribbon continues around the planet , but the transverse wave does not ; instead it seems highly damped on one side and well defined on the other . this can be seen from images in fig . [ fig : imsamples ] , specifically pairs taken on successive nights , which look at opposite sides of the planet . for example , compare pairs b - d , j - l , n - p , and r - t . in the last case , instead of the transverse wave , we see small discrete bright features in the same latitude region . these characteristics are more clearly evident in the rectangular maps of fig . [ fig : rectpro ] , especially in the 2012 maps . .,title="fig:",width=336 ] .,title="fig:",width=336 ] ribbon waves have also been seen in the cloud forms on saturn , one located at the peak of a mid - latitude eastward jet in the northern hemisphere @xcite and one located near the peak of an eastward jet in the southern hemisphere @xcite . the latter waves had peak - to - peak amplitudes of 1 - 1.3 in latitude , and wavelengths of 5 - 6 in longitude , smaller than the waves we observed on uranus by a factor of two in amplitude and a factor of four in wavelength . the mechanism suggested to explain the saturnian waves is baroclinic instability @xcite . a viable mechanism that might explain the uranian ribbon wave remains to be determined . to investigate the latitudinal band patterns over the whole globe we sampled our mosaicked images in narrow latitude bands , computing both zonal means and zonal median values to avoid the contributions of bright cloud features . the results from each time period are shown in fig . [ fig : zonalimage ] in image form and in fig . [ fig : latprofile ] as normalized plots . the zonal average , shown in the top panel in fig . [ fig : zonalimage ] includes the effect of discrete cloud features , and the bright bands in the 2014 image are due to the eruption in cloud activity during that year . the median images ( lower panel ) are much less affected by discrete cloud features and yet show many of the same persistent patterns , especially the brighter bands near 40 - 50s , 10 - 20s , 0 - 8n , 10 - 12n , 18 - 31n , 38 - 42n , and 48 - 52n . the exceptions are mainly for the 2014 observations where the large number of discrete features has apparently obscured the background band patterns in the northern hemisphere . the plots of latitudinal profiles in fig . [ fig : latprofile ] make clear how subtle the patterns really are . these features can not be directly discerned in the direct averages and median profiles shown in panel a. they only become obvious when the profiles have their smoothed versions subtracted , and the difference amplified by a factor of 100 , as in panels b and c. the large scale relative changes in panel a with latitude are somewhat distorted by the variation of effective view angle with latitude in the mosaicked images , especially at high southern latitudes , where the effective view angle cosines are of necessity much smaller than for mid - latitudes and for all of the northern hemisphere . to examine this issue we formed a median image without remapping to a fixed time , then sampled latitudinal brightness profiles at fixed view angle cosines . at @xmath65 we found that in july 2012 the i / f at 50n was about 25% brighter than the equator when compared at the same view angles , but 18% brighter in the mosaicked images . the same comparison at 45s , found a ratio of 0.95 for the sampling at equal view angles , but 0.83 in our mosaicked image . however , the trend of increasing brightness with time at high northern latitudes is also seen when sampled at constant view angle , as is the trend of darkening with time at high southern latitudes , both with respect to equatorial values . the composition of the clouds is constrained by indirect measurements . spectral observations show that the main condensable in the upper troposphere is methane . at the pressures and temperatures of the brighter clouds ( about 1 bar and 77 kelvin ) it seems certain that they are mainly made of frozen methane particles . the deeper clouds , at pressures near 1.6 bars , are less certain . h@xmath66s is a good candidate for these clouds , along with nh@xmath64sh for the even deeper layers @xcite . the spectral filters used in our high - s / n observing program had to be very limited due to the time required to obtain high s / n ratios . besides our primary h filter , we also used hcont , ch4s , and limited k@xmath3 filters , to provide constraints on effective cloud altitudes ( see fig . 3 ) , although we can not constrain the many parameters of a detailed vertical structure model with these observations . effective altitudes were estimated for major features seen in 2014 images by @xcite , finding that the larger bright feature had effective cloud top pressures from as low as 300 mb to as high as 1.2 bars . from a similar analysis of northern high - latitude features in 2011 keck images , @xcite found cloud altitudes of 200 mb to 400 mb for the two brightest features , and found that the small polar cloud features ( many unresolved ) were at considerably higher pressures , most in the 1 - 2 bar range . since the latter analysis , it has been confirmed that the methane mixing ratio at high polar latitudes is depleted substantially in the upper troposphere relative to low latitudes @xcite . that implies that a more complex analysis is needed to interpret spectral constraints on cloud altitudes in the north polar region , which we leave for future work . for the moment , we can provide a qualitative view of relative cloud height differences using h and hcont images from our 2012 keck data set . in fig . [ fig:2012color ] , we display two color - composite images in which we assign hcont to blue and green color channels , and h to the red color channel . deep clouds are attenuated more in h than in hcont , so they appear to have a blue tint , while higher altitude clouds of low optical depth have relatively greater brightness increases above background in h than in hcont , thus appearing with a red tint , while optically thick high altitude clouds can appear equally bright in both channels , and thus can appear white , with appropriate display enhancements . among the high - altitude features , based on their visibility in k@xmath3 images , we find that b and c reached pressures less than one bar . no features reached that level in the southern hemisphere . we suspect that feature a may have reached that level in 2012 , but lacking any k@xmath3 images from that period , we need to carry out a full radiative transfer analysis to confirm it . its bright clouds were not visible in k@xmath3 images from 2013 and 2014 . feature f was the only feature prominent in amateur images from 2014 , which were typically taken with a 625-nm long - pass filter ( cut off by ccd response falloff ) . f is not a high - altitude feature ; it is not visible in keck k@xmath3 images , but apparently is of sufficient optical thickness to provide contrast at wavelengths with less methane absorption . at these wavelengths , the background atmosphere becomes too bright to allow detection of optically thin high - altitude features , even though they can be very prominent in k@xmath3 images . an analysis of cloud pressures for major 2014 features by @xcite shows that c4 ( their feature 1 ) reached levels of 420 - 720 mbar , that f ( their feature 2 ) did not extend much above 2 bars , while g ( their feature br ) had a complex structure with component elements reaching pressures from 300 - 700 mbar . there may be a connection between the numerous small , apparently convective , cloud features in the north polar region of uranus , and its circulation being solid - body over the region where this suggested convection occurs . if the static stability ( as measured by its brunt - vaisala frequency or its rossby deformation radius @xmath67 @xcite ) were large , then the planetary east - west flow would be expected to act as if were two - dimensional and quasi - geostrophic ( qg ) @xcite . in the mid - latitudes between 10and 60 in both hemispheres , we can show that the mean east - west flow is well - approximated with a qg model with an @xmath68 km and with a weak potential vorticity gradient , in accord with @xcite . a qg model does not approximate the flow well in the region of the equatorial jet , where the coriolis parameter passes through zero and where the east - west flow is likely to be more three - dimensional and driven by cellular motions such as a hadley cell @xcite . in addition , a qg model does not approximate the near solid - body rotation that we observe at the north polar region of uranus . on the other hand , if the north polar region has low static stability with intermittent , local convection and/or baroclinic instabilities , as suggested by the region s profuse clouds and by the fact that it recently passed from winter to summer ( see section [ sec : polemorph ] ) , then there is reason to expect that solid - body rotation would develop there . in modeling stars , it was traditionally believed that the turbulent mixing within convection zones made the convective regions of stars rotate as solid bodies @xcite . in fact , a number of different authors have argued that in convectively stable regions of stars with internal gravity waves or with baroclinic instabilities , such as the goldreich - schubert - fricke instability , the flow is driven to solid - body rotation @xcite . however , measurements of the rotation curves in our sun , using helioseismology ( c.f . , fig . 5 in @xcite ) show a more complex picture of rotation . solar observations , along with three - dimensional numerical simulations @xcite in which there is mixing , show that only polar regions within 20 30of the poles rotate as solid bodies . although there is differential rotation in the outermost surface of the sun , deeper , at the boundary of the convection zone and the radiative region ( which is a nearly spherical surface with constant pressure ) , there is near solid - body rotation . ( see the comparison between the surfaces of constant rotation and the location of the convective zone boundary in fig . 1 of @xcite ) . because we expect that clouds that we use in determining the east - west velocities or uranus are located near the boundary of its convective and radiative zones , it is the differential ( or lack thereof ) rotation curve at this boundary that is relevant to us . a simple argument by @xcite based on weak instability and the thermal wind equation explains the solid - body rotation at the poles and differential rotation elsewhere . his original argument required that the weak instability be due to magnetic fields , but later showed that _ any _ weak instability , including convective or baroclinic , would suffice @xcite . the decrease in the static stability at the north pole of uranus due to the cooling of the atmosphere during winter over the long season of darkness may be sufficient to allow weak , new baroclinic instabilities to form or old instabilities to strengthen and cause the north polar region to rotate as a solid body during its winter and spring . if this connection between solid body rotation and weak static stability is valid , then as the north polar region of uranus passes into summer , we would expect to observe a decrease in the number of clouds at the north polar region and an increase in its differential rotation . future observations should be capable of testing this hypothesis . the angular velocity acceleration needed to transform the polar circulation from the solid body form seen in north polar spring to the more complex form seen at southern hemisphere solstice might be produced by vertical advection of angular momentum from below or from poleward meridional motions , for which conservation of angular momentum would tend to increase angular velocity with decreasing distance to the pole . whether such a transformation actually takes place , and how effective these mechanisms might be in producing the speculated transformation remains to be determined . we reported on the analysis of an extensive data set of high - quality ao images acquired from keck and gemini observatories from 2012 through 2014 . further enhancement of image quality was obtained by averaging multiple images in a body fixed coordinate system , allowing the improvement of signal to noise ratios while avoiding the smear due to planet rotation . our results are summarized below . 1 . we made over 850 measurements of cloud features in high - s / n images from 2012 , 2013 , and 2014 . these are heavily weighted towards the northern hemisphere not only because the sub - earth and sub - solar latitudes were in the northern hemisphere , but also because uranus produced more cloud features there . the number of trackable cloud features in 2014 was exceptionally large compared to other years . gemini observations produced far fewer trackable features than keck observations , mainly due to the higher performance of the keck ao system as a result of its ability to use uranus as a wave - front reference . 2 . these observations revealed an active polar region , with many small cloud features of 600 - 800 km , comparable to the keck telescope s resolution . most of the features are bright , but a number of dark features were also seen of about the same size and mainly circular shape . these features are found between the north pole and about 55n . the small polar cloud features were seen in every year of high - s / n observations , but were most apparent in 4 - 5 november 2012 observations , where they seemed to have higher contrast and greater numbers . a sizable fraction of these features lived long enough to track on successive nights , providing an accurate determination of their wind speeds . our new measurements firmly established that the high - latitude zonal winds of uranus , between 60n and at least 83n , closely adhere to solid - body rotation at a rate of [email protected]/h westward relative to body - fixed coordinates . when winds are plotted in units of m / s , the transition to solid - body rotation appears as a zonal jet with a peak velocity of 260 m / s westward 4 . we were able to fill in details of the zonal profile in the 12n - 30n region , which has been under - sampled in prior data sets . 5 . binned wind measurements show a stair - step appearance at middle latitudes , suggesting that the wind profile may not be an entirely smooth function of latitude . we discovered a substantial difference between the near - equatorial motions of waves and those of small discrete cloud features , with the former moving at a speed of 0.4/h eastward and the latter at a speed of 0.1/h eastward . this may mean that the equatorial mass flow is much slower than previously inferred and that the waves move eastward faster than the zonal flow by 0.3/h . three symmetric ( even order ) legendre polynomial fits were derived from the new wind observations . one is based on essentially the entire data set . a second is based on observations including the wave motions but excluding the small discrete feature tracking that was obtained from the 2014 observations , and a third is based on observations that exclude the wave motion measurements . we also found that the preponderance of current and past observations are consistent with a north - south mid - latitude asymmetry in the zonal wind profile of uranus . using an asymmetric model to characterize this difference , we find that the maximum asymmetry amplitude is 0.09/h when all high accuracy observations from voyager onward are included , and 0.135/h , when all but 2012 - 2104 observations are included , with the main asymmetries peaking near @xmath230 . it appears that the asymmetry has decreased with time . we did not include in this analysis the enormous high - latitude asymmetry implied by the recent reanalysis of voyager images by @xcite . although there are no hst or groundbased wind measurements at high southern latitudes ( 50s - 90s ) , a recent reanalysis of 1986 voyager 2 uranus observations by @xcite has yielded wind results there that are very different from northern winds at corresponding northern latitudes . this large north - south asymmetry might be seasonal . however , only minimal changes have been seen in the north polar region between 2011 and 2014 , and at middle latitudes only tiny changes have been seen since 1986 . this argues against a large seasonal change in polar winds , though it can not be ruled out . we found two types of equatorial wave features . one type , seen in prior observations , as well as in our more recent observations , are diffuse bright features a few degrees north of the equator , spaced about 30to 40apart in longitude . the other kind of wave feature , not observed prior to these high s / n observations , is a transverse wave marked by a dark ribbon with a latitudinal width of about 1and a longitudinal wavelength of about 20 . however , the transverse wave amplitude , which is of the order of several degrees of latitude over about half of the planet s circumference , damps to nearly zero over the remaining longitude range . we found that zonal averages of brightness of polar cloud features has a latitudinal pattern in which brightness minima occur near 53.5n , 61n , 71.5n , and 78n . this is a good match to the apparent mixing ratio variations inferred by @xcite . more obvious patterns are seen at lower latitudes , but most are only visible with high - pass filtering . 12 . zonal maps made from images acquired on successive nights in august 2012 , november 2012 , august 2013 , and august 2014 , show persistent patterns , and six easily distinguished long - lived cloud features , which we were able to track for long periods that ranged from 5 months to over two years . two at similar latitudes are associated with dark spots , and move with the atmospheric zonal flow close to the location of their associated dark spot instead of following the flow at the latitude of the bright features . these features retained their morphologies and drift rates in spite of several close interactions . a second pair of features at similar latitudes also survived several close approaches . several of the long - lived features also exhibited equatorward drifts and latitudinal oscillations . 13 . among the high - altitude features , based on their visibility in k@xmath3 images , we find that b and c reached pressures less than one bar , and thus are likely at least partly composed of methane ice . no features reached that level in the southern hemisphere . we suspect that feature a reached that level in 2012 , but lacking any k@xmath3 images from that period we would need a full radiative transfer analysis to confirm it . there is a correlation between the region of polar `` convective '' cloud forms and the region of solid body rotation , both extending from about 60n to at least 83n . there are dynamical reasons to expect that these might be related , and that when the convection subsides , the winds might also change . as uranus moves towards its 2030 northern hemisphere summer solstice , a large seasonal shift in wind speeds should occur if the recent results of @xcite for the southern hemisphere indicate a seasonal asymmetry . what also might happen is that the cloud features that we currently use to track motions in this region either disappear or become obscured by an overlying haze , a result suggested by the fact that we have never seen near - ir cloud features in the south polar region . we can only hope that any seasonal changes will become observable before the tracers we use to observe them disappear . las , pmf , and hbh acknowledge support from nasa s planetary astronomy program ( grant nnx13ah65 g for las and pmf ) . las and pmf also acknowledge nasa keck observing support ( jpl grant 1485335 ) . we thank staff at the w. m. keck observatory , which is made possible by the generous financial support of the w. m. keck foundation . we thank those of hawaiian ancestry on whose sacred mountain we are privileged to be guests . without their generous hospitality none of our groundbased observations would have been possible . we also thank staff at the gemini observatory , which is operated by the association of universities for research in astronomy , inc . , under a cooperative agreement with the nsf on behalf of the gemini partnership : the national science foundation ( united states ) , the national research council ( canada ) , conicyt ( chile ) , the australian research council ( australia ) , ministrio da cincia , tecnologia e inovao ( brazil ) and ministerio de ciencia , tecnologa e innovacin productiva ( argentina ) . we thank erich karkoschka for providing his tabulated correlation results in advance of publication . , m. , beebe , r. f. , conrath , b. j. , hinson , d. p. , ingersoll , a. p. , 1991 . uranus atmospheric dynamics and circulation . in : bergstralh , j. t. , miner , e. d. , matthews , m. s. ( eds . ) , uranus . university of arizona , tucson , pp . 253295 . , b. a. , ahearn , m. f. , bowell , e. , conrad , a. , consolmagno , g. j. , courtin , r. , fukushima , t. , hestroffer , d. , hilton , j. l. , krasinsky , g. a. , neumann , g. , oberst , j. , seidelmann , p. k. , stooke , p. , tholen , d. j. , thomas , p. c. , williams , i. p. , 2011 . report of the iau working group on cartographic coordinates and rotational elements : 2009 . mech . & dyn . 109 , 101135 . , i. , sromovsky , l. , hammel , h. b. , fry , p. m. , lebeau , r. p. , rages , k. a. , showalter , m. r. , matthews , k. , 2011 . post - equinox observations of uranus : berg s evolution , vertical structure , and track towards the equator . icarus 215 , 332345 . , p. m. , sromovsky , l. a. , rages , k. a. , hammel , h. b. , de pater , i. , 2012 . uranus high signal - to - noise ratio near - ir imaging : recent results . in : aas / division for planetary sciences meeting abstracts . 44 of aas / division for planetary sciences meeting abstracts . p. # 412.20 . , h. b. , sromovsky , l. a. , fry , p. m. , rages , k. , showalter , m. , de pater , i. , van dam , m. a. , lebeau , r. p. , deng , x. , 2009 . the dark spot in the atmosphere of uranus in 2006 : discovery , description , and dynamical simulations . icarus 201 , 257271 . , c. c. , baker , e. , barbara , j. , beurle , k. , brahic , a. , burns , j. a. , charnoz , s. , cooper , n. , dawson , d. d. , del genio , a. d. , denk , t. , dones , l. , dyudina , u. , evans , m. w. , giese , b. , grazier , k. , helfenstein , p. , ingersoll , a. p. , jacobson , r. a. , johnson , t. v. , mcewen , a. , murray , c. d. , neukum , g. , owen , w. m. , perry , j. , roatsch , t. , spitale , j. , squyres , s. , thomas , p. , tiscareno , m. , turtle , e. , vasavada , a. r. , veverka , j. , wagner , r. , west , r. , 2005 . cassini imaging science : initial results on saturn s atmosphere . science 307 , 12431247 . , b. a. , soderblom , l. a. , beebe , r. , bliss , d. , brown , r. h. , collins , s. a. , boyce , j. m. , briggs , g. a. , brahic , a. , cuzzi , j. n. , morrison , d. , co - authors , 1986 . voyager 2 in the uranian system - imaging science results . science 233 , 4364 . , l. a. , fry , p. m. , hammel , h. b. , , de pater , i. , rages , k. a. , showalter , m. r. , merline , w. j. , tamblyn , p. , neyman , c. , margot , j .- l . , fang , j. , colas , f. , dauvergne , j .- l . , gomez - forrellad , j. m. , hueso , r. , sanchez - lavega , a. , stallard , t. , 2012 . episodic bright and dark spots on uranus . icarus 220 , 622 . , l. a. , fry , p. m. , hammel , h. b. , de pater , i. , rages , k. a. , 2012 . first views of north polar clouds and circulation on uranus . in : aas / division for planetary sciences meeting abstracts . p. abstract # 504.01

we imaged uranus in the near infrared from 2012 into 2014 , using the keck / nirc2 camera and gemini / niri camera , both with adaptive optics . we obtained exceptional signal to noise ratios by averaging 8 - 16 individual exposures in a planet - fixed coordinate system . these noise - reduced images revealed many low - contrast discrete features and large scale cloud patterns not seen before , including scalloped waveforms just south of the equator , and an associated transverse ribbon wave near 6s . in all three years numerous small ( 600 - 700 km wide ) and mainly bright discrete features were seen within the north polar region ( north of about 55n ) . two small dark spots with bright companions were seen at middle latitudes . over 850 wind measurements were made , the vast majority of which were in the northern hemisphere . winds at high latitudes were measured with great precision , revealing an extended region of solid body rotation between 62n and at least 83n , at a rate of 4.08@xmath0/h westward relative to the planet s interior ( radio ) rotation of 20.88/h westward . near - equatorial speeds measured with high accuracy give different results for waves and small discrete features , with eastward drift rates of 0.4/h and 0.1/h respectively . the region of polar solid body rotation is a close match to the region of small - scale polar cloud features , suggesting a dynamical relationship . the winds from prior years and those from 2012 - 2014 are consistent with a mainly symmetric wind profile up to middle latitudes , with a small asymmetric component of @xmath10.09/h peaking near @xmath230 , and about 60% greater amplitude if only prior years are included , suggesting a declining mid - latitude asymmetry . while winds at high southern latitudes ( 50s - 90s ) are unconstrained by groundbased observations , a recent reanalysis of 1986 voyager 2 observations by karkoschka ( 2015 , icarus 250 , 294 - 307 ) has revealed an extremely large north - south asymmetry in this region , which might be seasonal . greatly increased activity was seen in 2014 , including the brightest ever feature seen in k@xmath3 images ( de pater et al . 2015 , icarus 252 , 121 - 128 ) , as well as other significant features , some of which had long lives . over the 2012 - 2014 period we identified six persistent discrete features . three were tracked for more than two years , two more for more than one year , and one for at least 5 months and continuing . several drifted in latitude towards the equator , and others appeared to exhibit latitudinal oscillations with long periods . we found two pairs of long - lived features that survived multiple passages within their own diameters of each other . zonally averaged cloud patterns were found to persist over 2012 - 2014 . when averaged over longitude , there is a brightness variation with latitude from 55n to the pole that is similar to effective methane mixing ratio variations with latitude derived from 2012 stis observations ( sromovsky et al . 2014 , icarus 238 , 137 - 155 ) .

near the big bang or big crunch singularity , the matter density and the space - time curvature become arbitrarily large . it is generally believed that in this regime , quantum effects should come into play , which could even prevent the formation of the singularity . this effect has first been analzyed in @xcite for classical gravity coupled to a second quantized matter field ; see also @xcite . for a quantized gravitational field , this effect has been studied in @xcite , and it was worked out in more detail in the framework of string cosmology @xcite and in loop quantum gravity @xcite . in contrast to the above approaches , we are here more modest and work with classical gravity coupled to dirac wave functions , without using second - quantized fields . we find a new mechanism , based on the oscillations of the spin of the matter field , which tends to prevent the formation of a space - time singularity . the mechanism can be understood as a _ spin condensation _ effect . an advantage of our model is that it is very simple and can be analyzed without any approximations . the dirac field could be interpreted physically as a new fermionic particle which becomes significant on the cosmological scale . alternatively , the dirac field can be understood similar to a `` quintessence '' @xcite as effectively describing unknown fields acting in our universe on the large . describing such a cosmological field by the dirac equation seems physically natural and changes the behavior of the cosmological model drastically near the big bang or big crunch , where quantum oscillations can prevent the formation of space- time singularities depending on the initial conditions . such a bounce back may happen several times , before , generically , the solution collapses . for brevity we here restrict attention to the case of a closed universe . however , the flat and hyperbolic cases are less interesting , since they expand infinitely . we remark that the hyperbolic case allows for solutions with negative energy density where the matter turns to be repulsive ( see @xcite ) . for the derivation of the equations we follow the standard approach in @xcite where we work with a torsion free connection ( for the effect of torsion see the cosmological model in einstein - cartan theory @xcite ) . the einstein - dirac ( ed ) equations read @xmath0 where @xmath1 is the energy - momentum tensor of the dirac particles , @xmath2 is the gravitational constant , @xmath3 denotes the dirac operator , and @xmath4 is the dirac wave function ( we always work in natural units @xmath5 ) . for the metric we take the ansatz of the closed friedmann - robertson - walker ( frw ) geometry @xmath6 where @xmath7 is the time for an observer at rest , @xmath8 is the scale function , and @xmath9 is the line element on the unit @xmath10-sphere , @xmath11 where @xmath12 is a radial variable , and @xmath13 are the angular variables . the dirac operator in this metric can be written as ( see @xcite ) @xmath14 where @xmath15 is the usual @xmath16 dirac matrix , and @xmath17 is the dirac operator on the unit @xmath10-sphere . the operator @xmath17 has discrete eigenvalues @xmath18 , corresponding to a quantization of the possible momenta of the dirac particles . for a given eigenvector @xmath19 , we can separate the dirac equation with the ansatz @xmath20^{-\frac{1}{2 } } \left ( \begin{matrix } \alpha(t ) \:\psi_{\lambda}(r,\vartheta,\varphi ) \\ \beta(t ) \:\psi_\lambda(r,\vartheta,\varphi ) \end{matrix } \right ) , \ ] ] thus describing the time dependence of the wave function by two complex functions @xmath21 and @xmath22 . in order to be consistent with the homogeneous and isotropic ansatz of the metric , the dirac spinors must also be in a homogeneous and isotropic configuration . in analogy to the method employed in @xcite for spherical symmetry , this can be achieved by taking an anti - symmetrized product of the wave functions ( [ ansatz ] ) , where @xmath23 runs over an orthonormal basis of the eigenspace corresponding to a fixed @xmath24 , where the symmetry is expressed by the fact that @xmath25 , with the sum running over all corresponding angular quantum numbers . we thus obtain a fermionic hartree - fock state composed of @xmath26 particles . the energy momentum tensor @xmath1 can be derived in a similar way as in @xcite , see equ . ( 4.4 ) . by spherical symmetry the components @xmath27 have to vanish as well as the components @xmath28 , which is due to the homogeneity in space . therefore @xmath1 is a diagonal matrix where the space components are equal , again due to the fact that our system is homogeneous in space . analogously to @xcite we derive the time component of the energy momentum tensor , which reads @xmath29 is constant in space , since the sum runs over the angular quantum numbers corresponding to @xmath24 , we obtain that @xmath30.\ ] ] substituting the ansatz and into the ed equations , we obtain the following system of odes in the spinors @xmath31 and the scale function @xmath8 ( for a detailed derivation see @xcite ) , @xmath32 let us mention that the equations obtained from the spacial components of the energy - momentum tensor are automatically satisfied due to the continuity equation , for which reason we omitted its exact form . let us emphasize again that all particles in our model have the same momentum @xmath24 and therefore give rise to the same spinor equation , meaning they are represented by the same spinor @xmath33 . this is what we mean by the above - mentioned notion of _ spin condensation_. note that ( [ einstein ] ) determines @xmath34 only up to a sign , and at first sight this seems to lead to an ambiguity whenever @xmath34 becomes zero . however , @xmath34 becomes uniquely determined by demanding that @xmath8 be twice differentiable , implying that @xmath34 must change sign at every zero of @xmath34 . normalizing the probability integral to one , we obtain the condition @xmath35 ) , one sees that this normalization condition is indeed time independent . a short calculation shows that the equations ( [ dirac ] , [ einstein ] ) are for any @xmath36 invariant under the scalings @xmath37 since this scaling changes the norm of the spinors , it is no loss of generality to replace ( [ norm1 ] ) by the simpler condition @xmath38 ) equals one . the resulting ed system involves the physical parameters @xmath39 ( the rest mass of the dirac particles ) and @xmath24 ( the dirac momentum , also related to the number of particles ) , as well as two free parameters to set the initial conditions of the spinors @xmath21 and @xmath22 . these four parameters describe all the physical configurations of our system . for the analysis of the system of odes ( [ dirac ] , [ einstein ] ) it is convenient to regard the spinor @xmath31 as a two - level quantum state , and to represent it by a bloch vector @xmath40 . more precisely , introducing the @xmath10-vectors @xmath41 ( where @xmath42 are the pauli matrices , and @xmath43 are the standard basis vectors in @xmath44 ) , the ed equations become @xmath45 ( where ` @xmath46 ' and ` @xmath47 ' denote the cross product and the scalar product in euclidean @xmath44 , respectively ) . to further simplify the equations , we introduce a rotation @xmath48 around the @xmath49-axis , such that @xmath50 becomes parallel to @xmath51 , @xmath52 then the vector @xmath53 satisfies the equations @xmath54 where @xmath55 we refer to the two equations in ( [ bloch ] ) as the dirac and einstein equations in the bloch representation , respectively . notice that equation can only have solutions if @xmath56 is negative . in the bloch representation , one can most easily recover the dust and radiation dominated frw - geometries . in the two limiting cases @xmath57 and @xmath58 , the second term in ( [ ddef ] ) drops out , and thus the ed equations simplify respectively to @xmath59 in both cases , the dirac equation describes a rotation around the fixed axis @xmath51 . this implies that @xmath56 is constant in time , and thus the einstein equations reduce to the well - known friedmann equations for a radiation dominated universe and a dust universe , respectively . note that the components @xmath60 and @xmath61 do oscillate due to quantum effects . these oscillations can be understood as the familiar `` zitterbewegung '' of dirac particles . but these quantum oscillations do not enter the einstein equations . away from the above limiting cases , the function @xmath56 is in general not constant , but it takes part in the oscillations as described by the first equation in . as a consequence , the dynamics can no longer be described by a single friedmann equation , but only by the coupled system of einstein - dirac equations . the relevant length scale is characterized by the radius @xmath62 on this length scale , the quantum oscillations do enter the einstein equations , leading to effects which go beyond the scope of classical cosmology . we point out that the radius @xmath63 can be much larger than the planck length . thus , in contrast to @xcite , our mechanism is not related to quantum gravity ; instead we are working consistently within the framework of einstein s general theory of relativity . using a standard ode solver , we shoot for numerical solutions starting at the point where the scale function @xmath8 reaches its maximum @xmath64 , solving forward and backwards in time , until we reach a big crunch or big bang singularity , respectively . in figure [ figcrunch ] a typical solution is shown . the function @xmath8 increases after the big bang similar as in the classical frw solution up to its maximal value @xmath64 , where it starts decreasing . , @xmath65 and @xmath66.,title="fig:",width=226 ] @xmath67 , @xmath65 and @xmath66.,title="fig:",width=226 ] + , @xmath65 and @xmath66.,title="fig:",width=226 ] @xmath67 , @xmath65 and @xmath66.,title="fig:",width=226 ] the classical contraction stops on the scale @xmath68 , where the quantum oscillations become important . this leads to an oscillatory behavior of @xmath8 . as a consequence , the sign of @xmath34 may flip at some minimal radius @xmath69 , where the universe again begins to expand , going over to a classical frw - like space - time . the functions @xmath60 and @xmath61 oscillate , with slightly varying amplitude . the function @xmath56 is nearly constant in the classical region , but becomes oscillatory near the quantum regime @xmath68 ( see figure [ figcrunch ] ) ; its nonlinear interplay with the scale function @xmath8 leads to the surprising effect that the big crunch is avoided . the behavior in the quantum regime depends crucially on the phase @xmath70 of the dirac oscillations , defined by @xmath71 . in figure [ figprob ] the minimal radius @xmath69 is plotted as a function of the initial value of @xmath70 . for @xmath72 , @xmath65 and @xmath66.,width=302 ] if @xmath73 , the big crunch is avoided and @xmath8 `` bounces back , '' whereas in the case @xmath74 the big crunch appears despite the quantum effects . considering the phase @xmath70 as unknown , one can give the result of figure [ figprob ] a statistical interpretation : for a random initial phase , this bounce appears with a finite probability ( in the example of figure [ figprob ] , this probability has the value @xmath75 ) . let us briefly discuss the qualitative dependence of the bounce on the free parameters @xmath64 , @xmath63 , @xmath24 , and @xmath70 of our model ( for a detailed analysis we refer to @xcite ) . first of all , the probability of preventing the crunch can be increased by choosing @xmath76 smaller . this is shown in the example figure [ fignocrunch ] , where the bounce occurs even with probability one . , @xmath65 and @xmath77.,title="fig:",width=226 ] @xmath67 , @xmath65 and @xmath77.,title="fig:",width=226 ] we point out that small @xmath76 does not imply that @xmath64 is also small . namely , as one sees from the einstein equation in ( [ bloch ] ) by setting @xmath34 equal to zero , a small value of @xmath76 can be compensated by choosing @xmath39 or @xmath24 large . this leaves us the freedom to choose @xmath63 , ( [ rqudef ] ) , at will . in this way , one can construct space - times with a high probability of bouncing in the physically relevant case where @xmath64 is the size of our universe and @xmath63 is a microscopic length scale . an interesting limiting case of our ed equations is obtained by dropping the first summand in ( [ ddef ] ) . this is a good approximation in the so - called _ scale dominated region _ where @xmath8 decreases so fast that the oscillations of @xmath60 and @xmath61 can be neglected . in particular , the scale dominated region describes the bounce in the physically interesting limit @xmath78 ( for fixed @xmath24 ) . in this limiting case , we can integrate the dirac equation in ( [ bloch ] ) explicitly and express @xmath79 as a function of @xmath8 , @xmath80 where @xmath81 + \arctan[r(t_0)/r_{\rm qu}]$ ] , and @xmath82 is the time from which on the scale dominated approximation applies . for the probability @xmath83 that the crunch is avoided one obtains @xmath84 this probability tends to @xmath85 as @xmath86 tends to infinity , showing that the bounce is of significance even for fixed @xmath76 in an arbitrarily large universe . by iteratively adjusting the starting values at @xmath87 , we constructed time - periodic solutions . in figure [ figperiod ] an example of a time - periodic solution is shown . except near the `` quantum turning points '' between collapse and expansion , the space - time is well - approximated by the classical dust - dominated frw universe . it is remarkable that the dominant energy condition is fulfilled even near the quantum turning points , as is shown on the right of figure [ figperiod ] . we point out that the periodic solutions were constructed by fine - tuning the initial condition and are thus not generic . a generic solution collapses after a finite number of cycles . , @xmath88 , @xmath89.,title="fig:",width=245 ] , @xmath88 , @xmath89.,title="fig:",width=283 ] a new class of solutions of the einstein equations coupled to dirac spinors was constructed . these solutions satisfy the dominant energy condition and are thus physically relevant . our model reveals in a simple and explicit setting a general mechanism which tends to avoid space - time singularities , such as the big bang or the big crunch , if the quantum mechanical nature of matter is taken into account . by fine - tuning the initial conditions our model even allows for periodic solutions , an eternal universe with an infinite number of cycles . _ acknowledgements . _ we thank the referees for helpful comments . we are grateful to the vielberth foundation , regensburg , for generous support . c.h . would like to thank the erwin schrdinger institute , vienna .

we consider a spatially homogeneous and isotropic system of dirac particles coupled to classical gravity . the dust and radiation dominated closed friedmann - robertson - walker space - times are recovered as limiting cases . we find a mechanism where quantum oscillations of the dirac wave functions can prevent the formation of the big bang or big crunch singularity . thus before the big crunch , the collapse of the universe is stopped by quantum effects and reversed to an expansion , so that the universe opens up entering a new era of classical behavior . numerical examples of such space - times are given , and the dependence on various parameters is discussed . generically , one has a collapse after a finite number of cycles . by fine - tuning the parameters we construct an example of a space - time which satisfies the dominant energy condition and is time - periodic , thus running through an infinite number of contraction and expansion cycles .

LOS ANGELES (Variety.com) - Denzel Washington hit the bullseye again. “The Magnificent Seven,” the Oscar-winner’s first western, topped the box office, picking up a solid $35 million. Hollywood’s star system has shriveled in the past decade, with few new talents emerging to reanimate the ranks and stand alongside Leo and Julia and Johnny and George and Brad. Some of their stars have dimmed, but Washington’s still shines brightly. He hasn’t had a film open to less than $20 million since 2007’s “The Great Debaters.” He’ll be back on screens at the end of the year in “Fences,” an adaptation of August Wilson’s play, that he directs and stars in alongside Viola Davis. It is expected to be an Oscar contender. “The Magnificent Seven” easily snagged the crown from “Sully,” the retelling of the “Miracle on the Hudson” landing that topped the box office for two weeks. The drama slid to third place with $13.8 million, bringing its stateside total to a healthy $92.4 million. “Storks,” an animated comedy from Warner Bros., came in second with $21.8 million. It’s a disappointing result given that the picture had been tracking to open to $30 million or higher. The film centers on a group of storks who have transitioned from baby delivering to hauling packed for an e-commerce behemoth. Andy Samberg, Kelsey Grammer, Jennifer Aniston, Keegan-Michael Key, and Jordan Peele are among the recognizable voices providing some of the film’s aural texture. The film cost $70 million to produce and is part of Warner Bros. effort to reinvigorate its animation division after the studio scored a hit with 2014’s “The Lego Movie.” It had more or less abandoned the genre to the likes of Disney and DreamWorks Animation, before undergoing a course correction. “The Magnificent Seven’s” success is welcome news for Metro-Goldwyn-Mayer, which was body checked this summer after “Ben-Hur,” its $100 million-plus Biblical epic, collapsed at the box office, resulting in at least $70 million in losses for the studio and its production co-financiers. Earlier this month, MGM reduced its annual profit projections by roughly $50 million because of “Ben-Hur’s” failure. But “The Magnificent Seven” counts as a win for the company. It also proves the viability of remaking older films, provided their is some novel spin to provide. In this case, Washington and director Antoine Fuqua, were able to stage balletic shootouts that rivaled those in John Sturges’ original 1960 film. They also played up the diversity of their cast, rounding out the cast of mercenaries with South Korean actor Byung-hun Lee, Mexican actor Manuel Garcia-Rulfo, and Native American actor Martin Sensmeier. That multi-cultural aspect seemed to resonate in a post-#OscarsSoWhite era. Sony Pictures distributed “The Magnificent Seven” and teamed with MGM, LStar Capital, and Village Roadshow to finance the $90 million production. “Bridget Jones’s Baby” took fourth place with $4.5 million, pushing the romantic comedy’s domestic total to a lackluster $16.5 million after two weeks of release. “Blair Witch” rounded out the top five, earning just under $4 million and bringing its total to roughly $16 million. In limited release, “The Dressmaker,” an Australian comedy with Kate Winslet, opened to $180,522 in 38 locations. Broad Green is distributing the film on behalf of Amazon Studios. Disney’s “Queen of Katwe,” an inspirational drama about a chess prodigy from Uganda, debuted in 55 theaters to $305,000. It will expand next weekend to roughly 1,500 locations.

– Antoine Fuqua's The Magnificent Seven remake rode the star power of Denzel Washington to an estimated $35 million debut, topping North American ticket sales over the weekend. It's another win for Washington: Reuters notes that the A-lister hasn't had a movie open to less than $20 million since The Great Debaters in 2007. Sony Pictures' estimate Sunday for The Magnificent Seven had the film far ahead of the week's other new release, Warner Bros.' Storks. The animated movie, starring Andy Samberg as a baby-delivering stork, opened with $21.8 million, reports the AP. A remake of John Sturges' 1960 film, which itself was a remake of Akira Kurosawa's Seven Samurai, The Magnificent Seven slots in as one of the biggest openings for a Western ever. The genre-blending Cowboys & Aliens holds the Western record with a $36.4 million debut in 2011. In third place was Clint Eastwood's Sully, which took in $13.8 million in its third weekend.

Peter Thiel and Hulk Hogan won and Nick Denton lost, so Denton has to sell off Gawker Media via a bankruptcy auction next month. But Denton and his employees haven’t folded up shop. In fact, Denton says, the company is doing better than it was last year: Readership has bounced back after falling off earlier in the year, and the company is generating more money than it did in 2015, via advertising and e-commerce affiliate links. Denton says that Gawker Media’s overall revenue is running about 7 percent to 8 percent above last year’s level, and that the company, which lost money last year, has a “small operating profit in the first half” of 2016. Gawker Media’s sites are now attracting 62.2 million visitors monthly from the U.S., Denton said, citing traffic-counter Quantcast. That’s back to where it was in January. Denton didn’t disclose an overall revenue number. But documents filed as part of Gawker’s bankruptcy proceedings today show that Gawker Media LLC, the company’s U.S. subsidiary, generated $17.8 million in revenue through the first five months of this year, and recorded revenue of $48.7 million in 2015 and $43.8 million in 2014. Denton says that those numbers don’t include all of Gawker’s revenue, and that they aren’t calculated using standard accounting procedures, but via the method the court requires. But he says a comparable number for the same five-month period in 2015 would have been $15.8 million. Whatever the increase is, it’s counterintuitive, given the shellacking Gawker Media has taken in the last few months. It’s also good news for Denton. Gawker’s uptick could improve the price the company fetches via auction next month; in theory, if Denton ends up successfully appealing the privacy verdict Hogan and Thiel won earlier this year, he could end up with some of the sale price back in his pocket. That’s down the road, if it ever happens. In the near term, Denton has a business to run and an auction to watch. And tonight, he’s going to watch Thiel, the man who funded the court case that bankrupted him, speak at the Republican National Convention. Here’s any edited version of a conversation I had with him, via instant message, today: Nick Denton: Hey hey. Can we do now? (I have a lunch.) Peter Kafka: Yes. Are we talking or chatting? Denton: Let's chat to start. Kafka: I mean speaking on the phone or messaging, like this. Denton: Oh, let's message: Easier to paste in numbers. Kafka: Fine. Denton: So, yeah, $17,810,993.32 is the first five months for the LLC, in the format that the court asks for, which is not [Generally Accepted Accounting Principles]. On the same basis, the comparable period of 2015 was $15,786,699.27 — so a 12.8 percent increase. For the first half for the group as a whole, we expect to come in some 7-8 percent ahead. Small operating profit in first half — because of growth in revenues and reduction of 5 percent in operating expenses. Traffic at 62.2m U.S. uniques (Quantcast), up in last three months, back to January level. (Pretty much exact same trajectory as Vox Media.) Revenue lifted by commerce, especially. Amazon Prime Day gross sales [via affiliate links] were 63 percent up. Kafka: The Vox Media folks are very envious of your Prime Day numbers. Denton: I'm envious of Vox's premium brand advertising. I expect that, under new ownership, we'll see a strong rebound there. Anyway, all-in-all, a good performance against strong headwinds — and an excellent indicator for the future of the business once it is free of these legal entanglements. Kafka: Why do you think traffic and revenue have increased post-Hogan? It’s surprising. Denton: It's a testament to the power of the brands, particularly in categories like tech and video games. Gizmodo and Kotaku will both hit all-time highs this month. Kafka: Pokémon. Denton: Yes, that too. Conventions. Comic-Con coming up. A measurable lift from Google AMP. No hit from the Facebook algorithm change. Kafka: After the Hogan verdict and the bankruptcy filing, Vox Media hired one of your employees. I assume other publishers are talking to Gawker Media employees as well. How do you keep them at the company given the impending sale? Denton: Most of all, our people are battle-hardened. Now that it's clear that these lawsuits are driven by a Trump-supporting billionaire, we feel like we're fighting the good fight. And I think most people are looking forward to a secure existence within a larger media group. Kafka: Ziff-Davis, the stalking horse bidder in the auction, has indicated that they don't want to operate Gawker.com. Do you think whoever ends up buying the company will want to keep Gawker? And are you interested in buying Gawker back from Ziff or whoever the buyer turns out to be? Denton: I don't think it's wise for me to speculate. Ziff has agreed to buy all the properties. But Gawker.com has been doing great, too. First to the Melania supercut. Highest traffic since the focus on politics and culture. Kafka: So on the one hand, this all great for you since you're selling an asset that is improving. On the other hand, you have to sell your asset. Denton: Yeah, this is bittersweet. We will find a good owner for the brands and an employer for the people. But Gawker Media Group was the only truly independent digital media company, founded by a journalist, focused on a journalistic mission, beholden only to readers. The business and the people will thrive under new ownership, which will be sweet to watch, but Peter Thiel did succeed in forcing us to give up our financial independence, which is the bitter part. But hey, you guys do great work even with Comcast as a big investor. Kafka: Indeed! But it’s very different. Anything else before you lunch? Denton: Hmm, let me think. Oh, we're seeing some revenue lift from Facebook Instant Articles. Rising eCPMs. I have a theory: That strength in category is particularly important for traffic, commerce and ad deals. Such a surfeit of general news, with the explosion of millennial-oriented properties — and advertising targeted against categories and influencers tends to perform better. I assume you're seeing the same with The Verge and Polygon. Kafka: Gotta ask the folks who run those properties! But yes, that sounds reasonable. Oh. One other question: What are you doing during the Thiel speech tonight? Are you going to watch? Denton: Of course I'm going to watch. I've been invited to a couple of Thiel-watching parties. Thiel told Tyler Cowen that the really good ideas were "way more dangerous" than his belief in the power of monopolies. I hope he is as frank as possible about his really good ideas. Nick Denton discusses the Hulk Hogan sex tape in June ||||| Gawker founder Nick Denton filed for personal bankruptcy Monday, listing $10 million to $50 million in assets and $100 million to $500 million in debts. The filing comes after Denton exhausted appeals to prevent Hulk Hogan from collecting on a $140 million invasion of privacy award handed down by a Florida jury in March. Denton had asked for repeated reprieves because he is appealing the verdict. Denton’s largest creditor is Hulk Hogan. The internet entrepreneur owes the WWE champ $125 million on a $140 million jury award for posting a tape of the wrestler having sex with his best friend’s wife. The remaining $15 million is owed by Gawker. “On this bitter day for me, I am consoled by the fact that my colleagues will soon be freed from this tech billionaire’s vendetta,” Denton tweeted Monday. Denton was referring to PayPal founder Peter Thiel, who secretly funded Hogan’s lawsuit against Gawker. Thiel had a personal vendetta against Denton after Gawker outed him as gay in 2007. The personal bankruptcy, filed in Manhattan federal court Monday, also lists a potential $145 million in more payouts on pending lawsuits against Denton. The suits include a $100 million defamation claim by Chicago lawyer Meanith Huon, another $35 million defamation suit by actress Fran Drescher’s husband Shiva Ayyadurai, and a third $10 million case by journalist Ashley Terrill. Other items in the bankruptcy filing are a $11.5 million loan due to Silicon Valley Bank. The filing reveals that Denton has been struggling to stay afloat in recent months. Denton took out a $50,000 loan against his company 401(K), is carrying $18,000 in credit card debt and hasn’t paid a $1,200 Consolidated Edison bill or a $120 Time Warner cable charge. Court papers show that Denton failed to rent out his Soho apartment, which he recently listed for $15,000 a month. The pad is Denton only other asset aside from his 30 percent share in Gawker. The personal bankruptcy filing comes just weeks after Denton filed for bankruptcy on behalf of Gawker. The same judge, Stuart Bernstein, will be handling both cases. The gossip website is scheduled to be sold at an auction later this month. “Gawker Media Group’s resilient brands and people will thrive under new ownership, when the sale closes in the next few weeks,” Denton tweeted Monday. David Houston, Hogan’s lawyer said the filing spelled victory for his client. “Following a lengthy trial, a jury verdict and much legal maneuvering, the time has come for Nick Denton to accept responsibility for the decisions he made and the rewards he reaped based on the suffering and humiliation of others,” Houston said. “Mr. Denton has spent vast amounts of time and money attempting to dodge his responsibility and a judge has subsequently determined that he misled the court in these efforts. The appellate court, in which he has guaranteed victory over Mr. Bollea, is not the puppet he thought it would be,” Houston said, calling Hogan by his legal name Terry Bollea. “His bankruptcy has nothing to do with who paid Mr. Bollea’s legal bills, and everything to do with Denton’s own choices and accountability. If even one person has been spared the humiliation that Mr. Bollea suffered, this is a victory,” Houston said.

– Gawker founder Nick Denton filed for personal bankruptcy Monday amid the website's battle with Hulk Hogan. Denton listed $10 million to $50 million in assets and $100 million to $500 million in debts, the New York Post reports; Denton owes Hogan $125 million after a jury sided with the wrestler in an invasion of privacy lawsuit filed after Gawker posted Hogan's sex tape online. The jury awarded Hogan $140 million, and Gawker owes the wrestler the other $15 million. Gawker Media Group filed for bankruptcy in June and will be sold at auction this month. "Gawker Media Group’s resilient brands and people will thrive under new ownership, when the sale closes in the next few weeks. On this bitter day for me, I am consoled by the fact that my colleagues will soon be freed from this tech billionaire’s vendetta," Denton tweeted Monday, referring to PayPal founder Peter Thiel, who funded Hogan's lawsuit. Denton also confirmed the bankruptcy news. Denton is appealing Hogan's invasion of privacy award, but had exhausted all appeals to keep Hogan from beginning to seize his assets. In a recent interview, Denton said that despite the bankruptcy filing, Gawker Media Group is making more money than it was last year.

one of the attractive solutions of the hierarchy problem is the consideration of our 4-dimensional universe as a sub - manifold that is embedded in a higher dimensional space - time . the models of type add ( arkani - hamed , dimopoulos and dvali ) @xcite allow compactification radius of extra dimensions to be of macroscopic size @xcite . black holes whose horizon radius is much smaller than this characteristic length can be well described by solution for higher - dimensional static black hole @xcite . such black holes could be produced at the next - generation particle colliders , probably at energies of very low order @xmath5 @xcite . thus study of their properties is strongly motivated . the very important black hole characteristic is its quasi - normal ( qn ) spectrum : the set of complex frequencies ( see @xcite for review ) . the real parts of the qn modes are the frequency of oscillations , while the imaginary parts are their damping rates . these oscillations dominate on the intermediately late times of a perturbation evolution near a black hole . they do not depend on the initial perturbation , being defined by the black hole parameters only . while the qn spectrum of different objects in four - dimensional @xcite and higher dimensional @xcite cases was extensively studied for massless fields of different spin and for the perturbation of the metric itself , our knowledge about the massive field qn spectrum still has gaps . massive scalar field qn modes were studied only for four - dimensional black holes within wkb approximation @xcite , and later with continued fraction method of leaver @xcite . massive vector qnms were investigated for schwarschild-(anti ) de sitter black holes @xcite . massive dirac qnms were studied in @xcite . it was found that the behaviour of massive fields is quite different from that of the massless ones : qn spectrum of massive fields has infinitely long - living modes , called quasi - resonances @xcite . the late time behaviour of the the massive fields in black hole background is the same as in pure minkowski space - time . asymptotically late time behaviour of them does not depend on their spin , mass and multipole number @xcite . also massive fields demonstrate the so - called superradiant instability @xcite , which is absent for massless fields . this paper is dedicated to the study of the qn spectrum of the massive scalar field in a @xmath0-dimensional black hole background . note , that the scalar field is widely considered as a good model for physical fields when the effect of their spin is negligibly small . it appears also in cosmological models , and , as one of the fundamental states in string theories . the scalar field with the mass term can be also interpreted as a self - interacting scalar field within regime of small perturbations @xcite . also , the scalar field gains large effective mass when considered in models with extra dimensions of rs - type @xcite . we study the qn spectrum in this regime as well . this paper is organized as follows : in sec . [ sec.basic ] we present basic formulae and the method of numerical calculation of the quasi - normal modes , sec . [ sec.numerical ] is devoted to our numerical results and their comparison with those obtained in other works . finally , in sec . [ sec.conclusions ] we summarize the obtained results . the metric of the schwarzshild black hole in @xmath0-dimensions has the form @xcite : @xmath6 where @xmath7 here we used the quantities @xmath8 after separation of angular and time variables , the radial part of the massive scalar field equation can be reduced to the form : @xmath9 where @xmath10 @xmath11 is the overtone number , @xmath3 is the field mass . by definition , the quasi - normal modes are eigenvalues of @xmath12 with the boundary conditions which correspond to the outgoing wave at spatial infinity and the ingoing wave at the black hole horizon . in 4-dimensional case @xcite , these boundary conditions look like @xmath13 & r & \simeq c_- ( r - r_0)^{-\imo\omega } , \quad { \rm as } \quad r \rightarrow r_h\ , , \label{horizonbc4d}\end{aligned}\ ] ] where @xmath14 . the sign of @xmath15 should be chosen in order to remain in the same complex quadrant as @xmath12 . it turns out that the behaviour of the wave function in a higher dimensional background differs qualitatively from that in the 4-dimensional one . for @xmath16 the leading term of @xmath17 at infinity is of order @xmath18 , that is why the appropriate boundary conditions for @xmath16 have the form : @xmath19 & r & \simeq c_- ( r - r_0)^{-\imo\omega/(d-3 ) } , \quad { \rm as } \quad r \rightarrow r_h\ , . \label{horizonbc}\end{aligned}\ ] ] one should note , that these boundary conditions do not change the possibility of quasi - resonance existing ( see @xcite ) . to solve the equation ( [ radial ] ) , we use the continued fraction method @xcite . equation ( [ radial ] ) has an irregular singularity at spatial infinity @xmath20 and @xmath21 regular singular points : @xmath22 and the roots of the equation @xmath23 , one of them is the horizon at @xmath24 . thus the appropriate frobenius series have the following form : @xmath25 where @xmath26 is regular in the circle @xmath27 for @xmath28 . for higher @xmath0 , some of the singularities appear in the unit circle and one has to continue the frobenius series through some midpoints . this technique was recently developed in @xcite , but in the present work we were limited by @xmath28 . substituting ( [ singularity ] ) into ( [ radial ] ) , one can obtain a @xmath29-term recurrence relation for the coefficients @xmath30 @xmath31 each of the functions @xmath32 has an analytical form in terms of @xmath33 , @xmath34 and @xmath12 , for a specific dimensionality @xmath0 and each integer @xmath35 . we now decrease the number of terms in the recurrence relation @xmath36 by one , i. e. we find the @xmath37 , which satisfy the equation @xmath38 for @xmath39 , we can rewrite the above expression as @xmath40 subtracting ( [ subsre ] ) from ( [ srcre ] ) we find the relation ( [ finre ] ) explicitly . thus we obtain : @xmath41 & & c_{j , i}^{(k)}(\omega ) = c_{j , i}^{(k+1)}(\omega)-\frac{c_{k , i}^{(k+1)}(\omega)\ , c_{j-1,i-1}^{(k)}(\omega)}{c_{k-1,i-1}^{(k)}(\omega}\ , . \nonumber%\label{gausselimination}\end{aligned}\ ] ] this procedure is called _ gaussian eliminations _ , and allows us to determine the coefficients in the three - term recurrence relation @xmath42 & & c_{0,1}^{(3)}\,b_1+c_{1,1}^{(3)}\,b_0=0,\end{aligned}\ ] ] numerically for a given @xmath12 up to any finite @xmath34 . the complexity of the procedure is _ linear _ with respect to @xmath34 and @xmath43 . the requirement that the frobenius series be convergent at spatial infinity implies that @xmath44 which can be inverted @xmath45 times to give @xmath46 the equation ( [ invcf ] ) with _ infinite continued fraction _ on the right - hand side can be solved numerically by minimising the absolute value of the difference between the left- and right - hand sides . the equation has an infinite number of roots ( corresponding to the qn spectrum ) , but for each @xmath45 , the most stable root is different . in general , we have to use the @xmath45 times inverted equation to find the @xmath45-th qn mode . the requirement that the continued fraction be itself convergent allows us to limit its depth by some large value , always ensuring that an increase in this value does not change the final results within the desired precision . it turns out , that the convergence of the infinite continued fraction becomes worse if the imaginary part of @xmath12 increases with respect to the real part . this problem was circumvented by h .- nollert @xcite . to improve the convergence of the infinite continued fraction one can consider initial approximation for @xmath47 that for large @xmath45 can be expanded as @xmath48 since for the four - dimensional case the coefficients @xmath49 , @xmath50 and @xmath51 are known analytically , one can find @xmath52 from the equation @xmath53 the found expansion ( [ nollertexp ] ) could be used as an initial approximation for the `` remaining '' infinite continued fraction . in order to ensure the convergence of ( [ nollertexp ] ) for a given value of @xmath12 , one has to start from the found approximation deeply enough inside the continued fraction ( [ cfeq ] ) . it turns out , that the required depth is less than it would be if we start from some arbitrary value as the initial approximation . as mentioned in @xcite , quasi - resonances correspond to purely imaginary @xmath15 . thus the convergence of the continued fraction decreases dramatically , and one needs to use the described method for calculation of those frequencies . even though @xmath49 , @xmath50 and @xmath51 are not known analytically in the case under consideration , we are still able to find the expansion ( [ nollertexp ] ) directly from ( [ rrelation ] ) . after dividing the equation ( [ rrelation ] ) by @xmath54 and using the definition of @xmath55 , one can find @xmath56 the important is that the expression ( [ nollertexp ] ) should be defined without any indeterminations . since the infinite continued fraction is convergent , it is clear that @xmath57 is itself well - defined . our task is just to recover it from the equation ( [ nollerthd ] ) . it turns out that only determination of @xmath58 and @xmath59 could cause ambiguities : the first appears due to a lot of roots of the equation ( [ nollerthd ] ) and the second is connected with two possible signs of @xmath60 in ( [ nollertexp ] ) . fortunately , both ambiguities can be eliminated by using our knowledge about the properties of the series ( [ frobenius ] ) . let us consider them more precisely . for large @xmath45 @xmath61 , thus @xmath58 satisfies @xmath62 the equation ( [ c0eq ] ) has in general @xmath63 roots ( in fact there are repeated roots ) . one of the roots is _ always _ @xmath64 ( it is also repeated ) , implying the unit radius of convergence of the series ( [ frobenius ] ) . other roots appear due to the existing of additional singular points of the equation ( [ radial ] ) . thus we choose @xmath64 . after fixing @xmath64 one can find that @xmath65 the sign of @xmath66 can be recovered using the convergence of the series ( [ frobenius ] ) at spatial infinity ( @xmath67 ) . therefore : @xmath68 i. e. @xmath69 . since for large @xmath45 @xmath70 we find out that the real part of @xmath66 can not be negative . after the sign of @xmath66 is fixed , the other coefficients in ( [ nollertexp ] ) can be found without encountering indeterminations @xcite . thus we have now possibility to use ( [ nollertexp ] ) as an initial approximation for @xmath57 when @xmath71 . this allows us to improve the convergence of the infinite continued fraction near quasi - resonances . let us start from an important notion . since the black hole mass in @xmath0-dimensional space - time can not be measured in units of length , as in four - dimensional space - time , we measure all the values in units of the black hole horizon radius that is an observable quantity . in order to do this we multiply ( [ radial ] ) by @xmath72 and consider dimensionless quantities @xmath73 and @xmath74 . making use of the technique described in the previous section , we have found dependence of the quasi - normal modes on the field mass . from the figure [ fig.l=0 ] we see that for four- and five - dimensional cases increasing of @xmath73 gives rise to decreasing of the imaginary part of the fundamental quasi - normal frequency until reaching zero , while the real part changes insignificantly . as discussed in @xcite , when some threshold value of @xmath73 is exceeded , the particular quasi - normal mode disappears . the higher threshold value corresponds to the higher overtone number . since we reached purely real frequency numerically with some finite accuracy , we can not state that purely real frequencies exist in the spectrum . we are on position , that at least while @xmath73 tends to some threshold values , the quasi - normal ringing lifetime increases infinitely . for @xmath1 we observe that the imaginary part of the fundamental mode tends to zero asymptotically while the real part approaches @xmath3 . we observed the same behaviour for different multipole numbers . for @xmath75 it is shown on the figure [ fig.d=6 ] . the picture is similar for higher dimensional cases , but since massless field quasi - normal frequency has higher imaginary part , one needs to reach higher @xmath73 to see this tendency . even though the behaviour of the fundamental overtone is different for @xmath1 , the dependence on @xmath73 of higher overtones is qualitatively the same ( see figure [ fig.d=6.high ] ) as for @xmath76 and @xmath77 . also because all the equations depend on @xmath78 we observe that the contribution of mass for higher overtones is of order @xmath79 as in four - dimensional case @xcite . thus the asympotical behaviour of the high overtones does not depend on @xmath3 . from the figure [ fig.highqnms ] one can see that for 7-dimensional case the difference between massless and massive @xmath80 cases is insignificant already for 20th overtone . according to the analytical formula @xcite , the spectrum is asymptotically equidistant for all @xmath0 : @xmath81 and the real part approaches @xmath82 the difference in the mass dependence of the fundamental overtone for @xmath1 leads to another remarkable fact . since for high field mass the imaginary part of the fundamental overtone tends to zero only asymptotically ( see figure [ fig.l=0 ] ) , and the imaginary part of higher overtones reaches zero for some finite value of @xmath73 ( see figure [ fig.d=6 ] ) , there are some values of @xmath73 for which the imaginary parts of two overtones _ are the same_. after one of these values is reached the overtones can be distinguished only by their real part and the quasi - normal ringing has two dominant frequencies in its spectrum . it turns out that this could happen only for relatively large field mass , thus the imaginary part of those frequencies is very small : for example , for the field configuration of spherical symmetry ( @xmath83 ) in @xmath75 , the smallest value of @xmath84 , for which there are dominant modes with @xmath85 and @xmath86 . their imaginary parts are equivalently small , thus their lifetime is extremely high . thus one could observe the superposition of that two frequencies at late times of the quasi - normal ringing . one should note that this exotic behaviour was found for relatively large field mass for which the linear approximation ( i. e. without taking into consideration the back reaction of the field upon the black hole ) could not be good . the fundamental modes of massless scalar field for different @xmath0 are presented in table [ fundamentalmodes ] . we see that as @xmath0 increases , the real part of the fundamental overtone increases faster than the imaginary part . thus fields that live in the bulk are better oscillators than brane - localised ones @xcite , considered in the context of large extra dimension scenario ( see @xcite for review ) . .fundamental quasi - normal frequencies of massless scalar field ( measured in the units of the black hole horizon radius ) . [ cols="<,^,^,^",options="header " , ] we checked the correctness of our results by comparing them with those @xcite obtained with the help of the wkb method @xcite for higher values of the multipole number . the wkb method is known to give very accurate results in this regime @xcite . one should note also , that massless scalar field quasi - normal spectrum coincides with that of the metric perturbation of the tensor type for @xmath87 , which was recently studied @xcite . our results were obtained independently and demonstrate complete agreement . in the present paper we studied quasi - normal spectrum of the massive scalar field near the higher dimensional black hole within continued fraction method of leaver with improvement of nollert that was generalised for the case of @xmath43-term recurrence relation for frobenius series coefficients . we found that the fundamental modes for @xmath1 have qualitatively different dependence on the field mass : their real part approaches the field mass while the imaginary part tends to zero for high values of @xmath73 . at the same time , the behaviour of higher modes is qualitatively the same as for @xmath76 and @xmath77 cases : the imaginary part decreases quickly and the particular mode disappears after reaching some threshold value of @xmath73 . n. arkani - hamed , s. dimopoulos and g. r. dvali , phys . b * 429 * , 263 ( 1998 ) [ hep - ph/9803315 ] ; 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we study quasi - normal spectrum of the massive scalar field in the @xmath0-dimensional black hole background . we found the qualitatively different dependence of the fundamental modes on the field mass for @xmath1 . the behaviour of higher modes is qualitatively the same for all @xmath0 . thus for some particular values of @xmath2 , where @xmath3 is the field mass and @xmath4 is the black hole mass , the spectrum has two dominating oscillations with a very long lifetime . we show that the asymptotically high overtones do not depend on the field mass . in addition , we present the generalisation of the nollert improvement of the continued fraction technique for the numerical calculation of quasi - normal frequencies of @xmath0-dimensional black holes .

bothersome nocturia ( y nio ) reduces quality of life ( qol ) and can lead to embarrassment , social anxiety , and poor self - esteem . it is frequently associated with daytime drowsiness , inability to concentrate , and decreased motivation to perform activities . nocturnal polyuria ( np ) is an important cause of nocturia , and about 70% of outpatients with nocturia have np . although the detailed mechanism of np has yet to be elucidated fully , low serum arginine vasopressin levels during the night and high serum human atrial natriuretic peptide ( hanp ) levels can cause this condition . although prebedtime vasopressin treatment is widely applied to reduce nocturnal urine volume , adverse effects of hyponatremia are not uncommon . other options for np are the application of loop diuretics during the daytime and a japanese traditional blended herbal medicine , gosha - jinki - gan ( gjg ; j shng shn q wn ) . gjg has been used widely and empirically in japan to treat patients with lower urinary tract symptoms . since this herbal drug can be purchased over the counter , it is used as a traditional medicine for nocturia . however , to the best of our knowledge , there is little evidence on the efficacy of this drug for nocturia treatment . in this study , we attempted to evaluate the efficacy and safety of gjg as an add - on therapy for elderly patients with nocturia resistant to 1-blockers or antimuscarinic drugs . we evaluated patients based on their international prostate symptom score ( ipss ) , ipss - qol , benign prostatic hyperplasia impact index ( bii ) , uroflowmetry results , frequency volume chart ( fvc ) , serum hanp levels , and urinary 8-hydroxy-2-deoxyguanosine ( 8-ohdg ) levels . we obtained written informed consent from all the participants after thoroughly explaining the efficacy of gjg and its possible adverse reactions such as hypersensitivity , liver dysfunction , epigastric discomfort , and accelerated heart palpitations . for monitoring side effects , levels of aspartate aminotransferase , alanine aminotransferase , serum creatinine , urea nitrogen , uric acid , urinary blood , glucose , and ketone were investigated prior to and after treatment . gjg ( tj-107 ; tsumura co. , tokyo , japan ) is the extract product , which included 4.5 g of the compound extracts of 10 herbal medicines : rehmanniae radix ( d hung ) ( 5 g ) , achyranthis radix ( ni x ) ( 3 g ) , corni fructus ( shn zh y ) ( 3 g ) , dioscoreae rhizoma ( shn yo ) ( 3 g ) , hoelen ( poria cocos ; f ling ) ( 3 g ) , plantaginis semen ( ch qin z ) ( 3 g ) , alismatis rhizoma ( z xi ) ( 3 g ) , moutan cortex ( m dn p ) ( 3 g ) , cinnamoni cortex ( gu p ) ( 1 g ) , and heat - processed processi aconiti radix ( f z ) ( 1 g ) . it is a standardized spray - dried water extract , which includes magnesium stearate , lactose , and fructose fatty acid esters as diluents . patients who consulted our hospital with lower urinary tract symptoms between june 2013 and may 2014 were candidates for enrollment . inclusion criteria were as follows : ( 1 ) age 65 years ; ( 2 ) 2 voids per night despite treatment with 1-blockers or antimuscarinic drugs for at least 4 weeks ; ( 3 ) total ipss 8 ; and ( 4 ) ipss - qol 3 . patients with neurogenic bladder , urethral stricture , and active urinary tract infection possibly affecting voiding functions were excluded . all patients were administered gjg 2.5 g preprandially for 12 weeks as an add - on therapy to 1-blockers or antimuscarinic drugs . prior to and after treatment , fvc ( 3 consecutive days ) , ipss , ipss - qol , bii , uroflowmetry , hanp , and urinary 8-ohdg levels were examined . we then used the fvc data to calculate the void frequency and voided volume over 24 continuous hours . the np index was calculated by dividing nocturnal urine volume by the total urine volume per day , and hours of undisturbed sleep was defined as the duration between going to bed and the first nocturnal void . polyuria was defined as producing > 40 ml / kg urine over a 24-hour period , and np was defined as an np index score of > 0.33 . as a marker of oxidative stress , we evaluated urinary 8-ohdg levels using an icr-001 device ( techno medica , yokohama , japan ) according to the manufacturer s recommendations . data are reported as mean standard deviation and analyzed using spss software , version 12.0 ( ibm , chicago , il , usa ) . wilcoxon 's signed rank test was used to evaluate the effect of treatment , and p < 0.05 was considered significant . nocturnal frequency , urine volume , and np index were 4.4 1.3 ml , 951 504 ml and 0.45 0.14 ml , respectively . fvc scores revealed np in 25 patients ( 83.3% ) , decreased nocturnal bladder capacity in eight patients ( 26.7% ) , and both np and decreased nocturnal bladder capacity in five patients ( 16.7% ) . a summary of the effects of gjg on voiding functions is listed in table 2 . subjective outcomes assessed by total ipss , ipss - qol , and bii significantly decreased after treatment . both voiding symptoms ( intermittency , straining , weak stream , and incomplete emptying ) and storage symptoms ( urgency , micturition frequency , and nocturia ( y nio ) ) improved after treatment ( 6.4 4.4 vs. 4.3 3.2 , p = 0.011 and 8.1 2.9 vs. 6.1 2.0 , p = 0.002 , respectively ) . maximum flow rates and voided volume from the baseline did not change significantly after treatment from 10.7 10.0 to 10.3 8.2 , p = 0.800 , and from 108 73 to 113 68 , p = 0.812 , respectively . no significant change in postvoid residual was observed after treatment ( 26 26 to 24 23 , p = 0.735 ) . objective outcomes , which included the number of nocturnal voids and the urine production rate at night , were significantly decreased , from 4.4 1.3 to 3.5 1.9 , p = 0.008 and from 0.45 0.14 to 0.39 0.16 , p = 0.009 , respectively . however , other objective parameters , such as hours of undisturbed sleep , hanp , and urine 8-ohdg levels , remained unchanged . the symptoms were gastric discomfort in two patients and nausea in one ; all such cases were of mild severity ( grade 1 ) and were followed up closely without therapy . gjg , a pharmaceutical drug covered by national health insurance , has been effective for patients with lumbago , edema of the lower extremities , numbness , blurred vision , and lower urinary tract symptoms . kidney keep one s congenital energy , and , with aging , this function is deteriorated . studies have shown that either hachimi - jio - gan ( b wi d hung wn ) or gjg is effective for diabetic complications . yokozawa et al11 , 12 , 13 investigated that hachimi - jio - gan had a protective effect against diabetic nephropathy in animal models . they speculated that hachimi - jio - gan promotes the formation of advanced glycation end - product by corni fructus ( shn zh y ) or suppression of oxidative stress . moreover , gjg had shown protective effects against diabetic complications in the animal model or clinical setting.15 , 16 , 17 watanabe et al showed that gjg had some beneficial effects on serum glucose and glycated hemoglobin . comparing the medications in two groups , they found that the patients in the control group had more progressed medications in 5 years ( nonmedication to medication or medication to insulin ) . body mass index ( bmi ) was similar at the beginning of the study ; however , after 5 years , the gjg group retained their bmi and the control group lost weight . these two facts support that serum glucose was reduced in the gjg group , compared with the control group . because the difference in the blood serum glucose or glycated hemoglobin was observed only in the late years , they assumed that an improvement of insulin resistance might lead to a decrease in the blood glucose level.18 , 19 the mechanism of gjg for nocturia ( y nio ) has long been unclear . however , recent basic research is gradually clarifying the mechanism of gjg for urinary frequency.20 , 21 , 22 , 23 , 24 goto et al reported that the effects of gjg on urinary frequency are associated with inhibition of the micturition reflex and decline of bladder sensation via the spinal kappa - opioid receptors . among the ingredients of gjg , processi aconiti radix ( f z ) from aconitum carmichaelii may be mainly responsible for the antinociceptive effect . in addition , they hypothesized that other ingredients such as plantaginis semen ( ch qin z ) from plantago asiatica ( ch qin co ) , alismatis rhizoma ( z xi ) from alisma orientale , and poria ( f ling ) from poria cocos could be effective for reducing urine production at night by regulating the distribution of fluid in the body . oxidative stress induces pathophysiological conditions in the urinary bladder by damaging the urothelium and sensitizing bladder afferent signaling , and oxidative stress has been shown to induce bladder hyperactivity by mediating capsaicin - sensitive c - fibers . therefore , eliminating oxidative stress might ameliorate such pathophysiological conditions and be a possible therapy for nocturia due to lower urinary tract symptoms . as we did not evaluate the antioxidative effects of gjg , further long - term studies are needed to evaluate the effects of gjg as an antioxidative medicine . the major limitations of this study are the small number of patients , lack of a placebo - controlled group , and no urodynamic data . in cases of lower urinary tract symptoms , which have a strong placebo component therefore , it is difficult to conclude that gjg is effective for nocturia . to overcome these disadvantages , gjg exerts an inhibitory effect on the micturition reflex , and is a potentially safe and useful add - on treatment for patients with nocturia ( y nio ) resistant to 1-blockers or antimuscarinic drugs . however , further clinical investigations are required to elucidate the precise mechanisms of gjg in nocturia pathophysiology .

we evaluated the efficacy and tolerability of gosha - jinki - gan ( gjg ; j shng shn q wn ) in 30 cases of nocturia ( y nio ) unresponsive to 1-blockers or antimuscarinic drugs . all patients received gjg extract powder ( 2.5 g ) three times a day for 12 weeks as an add - on therapy to 1-blockers or antimuscarinic drugs . subjective outcomes assessed by the international prostate symptom score quality of life , and the benign prostatic hyperplasia impact index and objective outcomes assessed by urinary frequency and the urine production rate at night showed significant improvement after treatment . moreover , other objective outcomes assessed by maximum flow rates , postvoid residual , serum human atrial natriuretic peptide levels , and urinary 8-hydroxy-2-deoxyguanosine levels did not change . adverse events were observed in 10% of cases ; however , these events were mild . gjg appears to be a safe and effective potential therapeutic alternative for patients with nocturia unresponsive to 1-blockers or antimuscarinic drugs . further clinical investigations are required to elucidate the precise pathophysiologic mechanisms of gjg in nocturia .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Autism Statistics, Surveillance, Research, and Epidemiology Act of 1998 (ASSURE)''. SEC. 2. FINDINGS. The Congress makes the following findings: (1) Autism and other pervasive developmental disabilities (fragile X syndrome, Rett's syndrome, childhood disintegrative disorder, Landau-Kleffner syndrome, and pervasive developmental disorders not otherwise specified) are biologically based neurodevelopmental diseases which cause severe impairment in cognition, language, and affective abilities. (2) Autism and pervasive developmental disabilities are not rare; they may affect as many as one in every 500 children, and more than 500,000 Americans. (3) There is little information on the prevalence of autism and other pervasive developmental disabilities in the United States. There have never been any national prevalence studies in the United States, and the two studies that were conducted in the 1980s examined only selected areas of the country. Recent studies in Canada, Europe, and Japan suggest that the prevalence of classic autism alone may be 300 percent to 400 percent higher than previously estimated. (4) The cost of caring for individuals with autism and pervasive developmental disabilities is estimated at more than $13,000,000,000 per year for direct costs only. (5) Autism is considered by many scientists to be one of the most heritable of all the developmental disorders, and the most likely to yield to the latest scientific advancements in genetics and neurology. (6) The discovery of effective treatments and a cure for autism will be greatly enhanced when scientists and epidemiologists have an accurate understanding of the prevalence and incidence of autism. (7) Recent research suggests that environmental factors may contribute to autism. As a result, contributing causes of autism, if identified, may be preventable. (8) Finding the answers to the causes of autism and related developmental disabilities may help researchers to understand other disorders, ranging from learning problems, to hyperactivity, to communications deficits that affect millions of Americans. SEC. 3. DEVELOPMENTAL DISABILITIES SURVEILLANCE AND RESEARCH PROGRAMS. (a) National Autism and Pervasive Developmental Disabilities Surveillance Program.--The Secretary of Health and Human Services (in this Act referred to as the ``Secretary''), acting through the Director of the Centers for Disease Control and Prevention, may make awards of grants and cooperative agreements for the collection, analysis, and reporting of data on autism and pervasive developmental disabilities. An entity may receive such an award only if the entity is a public or nonprofit private entity (including health departments of States and political subdivisions of States, and including universities and other educational entities). In making such awards, the Secretary may provide direct technical assistance in lieu of cash. (b) Centers of Excellence in Autism and Pervasive Developmental Disabilities Epidemiology.-- (1) In general.--The Secretary, acting through the Director of the Centers for Disease Control and Prevention, shall (subject to the extent of amounts made available in appropriations Acts) establish not less than three, and not more than five, regional centers of excellence in autism and pervasive developmental disabilities epidemiology for the purpose of collecting and analyzing information on the number, incidence, correlates, and causes of autism and related developmental disabilities. (2) Recipients of awards for establishment of centers.-- Centers under paragraph (1) shall be established and operated through the award of grants or cooperative agreements to public or nonprofit private entities that conduct research, including health departments of States and political subdivisions of States, and including universities and other educational entities. (3) Certain requirements.--An award for a center under paragraph (1) may be made only if the entity involved submits to the Secretary an application containing such agreements and information as the Secretary may require, including an agreement that the center involved will operate in accordance with the following: (A) The center will collect, analyze, and report autism and pervasive developmental disabilities data according to guidelines prescribed the Director, after consultation with relevant State and local public health officials, private sector developmental disability researchers, and advocates for those with developmental disabilities; (B) The center will assist with the development and coordination of State autism and pervasive developmental disabilities surveillance efforts within a region; (C) The center will provide education, training, and clinical skills improvement for health professionals aimed at better understanding and treatment of autism and related developmental disabilities; and (D) The center will identify eligible cases and controls through its surveillance systems and conduct research into factors which may cause autism and related developmental disabilities; each program will develop or extend an area of special research expertise (including, but not limited to, genetics, environmental exposure to contaminants, immunology, and other relevant research specialty areas). SEC. 4. CLEARINGHOUSE. The Secretary, acting through the Director of the Centers for Disease Control and Prevention, shall carry out the following: (1) The Centers for Disease Control and Prevention shall serve as the coordinating agency for autism and pervasive developmental disabilities surveillance activities through the establishment of a clearinghouse for the collection and storage of data generated from the monitoring programs created by this Act. The functions of such a clearinghouse shall include facilitating the coordination of research and policy development relating to the epidemiology of autism and other pervasive developmental disabilities. (2) The Secretary, acting through the Centers for Disease Control and Prevention, shall coordinate the Federal response to requests for assistance from State health department officials regarding potential or alleged autism or developmental disability clusters. SEC. 5. ADVISORY COMMITTEE. (a) In General.--The Secretary shall establish an Advisory Committee for Autism and Pervasive Developmental Disabilities Epidemiology Research (in this section referred to as the ``Committee''). The Committee shall provide advice and recommendations to the Director of the Centers for Disease Control and Prevention on-- (1) the establishment of a national autism and pervasive developmental disabilities surveillance program; (2) the establishment of centers of excellence in autism and pervasive developmental disabilities epidemiology; (3) methods and procedures to more effectively coordinate government and non-government programs and research on autism and pervasive developmental disabilities epidemiology; and (4) the effective operation of autism and pervasive developmental disabilities epidemiology research activities. (b) Composition.-- (1) In general.--The Committee shall be composed of ex officio members in accordance with paragraph (2) and 11 appointed members in accordance with paragraph (3). (2) Ex officio members.--The following officials shall serve as ex officio members of the Committee: (A) The Director of the National Center for Environmental Health. (B) The Assistant Administrator of the Agency for Toxic Substances and Disease Registry. (C) The Director of the National Institute of Child Health and Human Development. (D) The Director of the National Institute of Neurological Disorders and Stroke. (3) Appointed members.--Appointments to the Committee shall be made in accordance with the following: (A) Two members shall be research scientists with demonstrated achievements in research related to autism and related developmental disabilities. The scientists shall be appointed by the Secretary in consultation with the National Academy of Sciences. (B) Five members shall be representatives of the five national organizations whose primary emphasis is on research into autism and other pervasive developmental disabilities. One representative from each of such organizations shall be appointed by the Secretary in consultation with the National Academy of Sciences. (C) Two members shall be clinicians whose practice is primarily devoted to the treatment of individuals with autism and other pervasive developmental disabilities. The clinicians shall be appointed by the Secretary in consultation with the Institute of Medicine and the National Academy of Sciences. (D) Two members shall be individuals who are the parents or legal guardians of a person or persons with autism or other pervasive developmental disabilities. The individuals shall be appointed by the Secretary in consultation with the ex officio members under paragraph (1) and the five national organizations referred to in subparagraph (B). (c) Administrative Support; Terms of Service; Other Provisions.-- The following apply with respect to the Committee: (1) The Committee shall receive necessary and appropriate administrative support from the Department of Health and Human Services. (2) Members of the Committee shall be appointed for a term of three years, and may serve for an unlimited number of terms if reappointed. (3) The Committee shall meet no less than two times per year. (4) Members of the Committee shall not receive additional compensation for their service. Such members may receive reimbursement for appropriate and additional expenses that are incurred through service on the Committee which would not have incurred had they not been a member of the Committee. SEC. 6. REPORT TO CONGRESS. The Secretary shall prepare and submit to the Congress, after consultation and comment by the Advisory Committee, an annual report regarding the prevalence and incidence of autism and other pervasive developmental disorders, the results of research into the etiology of autism and other pervasive developmental disorders, public health responses to known or preventable causes of autism and other pervasive developmental disorders, and the need for additional research into promising lines of scientific inquiry. SEC. 7. DEFINITION. For purposes of this Act, the term ``State'' means each of the several States, the District of Columbia, the Commonwealth of Puerto Rico, American Samoa, Guam, the Commonwealth of the Northern Mariana Islands, the Virgin Islands, and the Trust Territory of the Pacific Islands. SEC. 8. AUTHORIZATION OF APPROPRIATIONS. For the purpose of carrying out this Act, there is authorized to be appropriated $7,500,000 for each of the fiscal years 1999 through 2003.

Autism Statistics, Surveillance, Research, and Epidemiology Act of 1998 (ASSURE) - Authorizes grants and contracts for the collection, analysis, and reporting of data on autism and pervasive developmental disabilities. Mandates establishment of three to five regional centers of excellence in autism and pervasive developmental disabilities epidemiology to collect and analyze information, to be established and operated through grants or cooperative agreements. Requires that the Centers for Disease Control and Prevention serve as the coordinating agency for autism and pervasive developmental disabilities surveillance through the establishment of a clearinghouse for data generated from the monitoring programs created by this Act. Mandates establishment of an Advisory Committee for Autism and Pervasive Developmental Disabilities Epidemiology Research. Authorizes appropriations.

in the past few years there has been increasing interest in the investigation of financial markets as complex systems in statistical mechanics . the empirical analysis of the high frequency financial data reveals nonstationary statistics of market fluctuations and several mathematical models of markets based on the concept of the nonequilibrium phenomena have been proposed @xcite . recently mizuno _ et al . _ investigate high frequency data of the usd / jpy exchange market and conclude that dealers perception and decision are mainly based on the latest 2 minutes data @xcite . this result means that there are feedback loops of information in the foreign currency market . as microscopic models of financial markets some agent models are proposed @xcite . specifically ising - like models are familiar to statistical physicists and have been examined in the context of econophysics . the analogy to the paramagnetic - ferromagnetic transition is used to explain crashes and bubbles . _ consider the effect of a weak external force acting on the agents in the ising model of the financial market and conclude that apparently weak stimuli from outside can have potentially effect on financial market due to stochastic resonance @xcite . this conclusion indicates that it is possible to observe the effect of the external stimuli from the market fluctuations . motivated by their conclusion we investigate high - frequency financial data and find a potential evidence that stochastic resonance occurs in financial markets . in this article the results of data analysis are reported and the agent - based model is proposed in order to explain this phenomenon . we analyze tick quotes on three foreign currency markets ( usd / jpy , eur / usd , and jpy / eur ) for periods from january 1999 to december 2000 @xcite . this database contains time stamps , prices , and identifiers of either ask or bid . since generally market participants ( dealers ) must indicate both ask and bid prices in foreign currency markets the nearly same number of ask and bid offering are recorded in the database . here we focus on the ask offering and regard the number of ask quotes per unit time ( one minute ) @xmath0 as the market activity . the reason why we define the number of ask quotes as the market activity is because this quantity represents amount of dealers responses to the market . in order to elucidate temporal structure of the market activity power spectrum densities of @xmath0 , estimated by @xmath1 where @xmath2 represents frequency , and @xmath3 a maximum period of the power spectrum density , are calculated . fig : power - spectrum - usdjpy ] , [ fig : power - spectrum - eurusd ] , and [ fig : power - spectrum - eurjpy ] show the power spectrum densities for three foreign currency markets ( usd / jpy , uer / usd , and eur / jpy ) from january 1999 to december 2000 . it is found that they have some peaks at the high frequency region . there is a peak at 2.5 minutes on the usd / jpy market , at 3 minutes on the eur / usd market , and there are some peaks on the jpy / eur . we confirm that these peaks appear and disappear depending on observation periods . on the usd / jpy market there is the peak for periods of january 1999july 1999 , march 2000april 2000 , and august 2000november 2000 ; on the eur / usd market july 1999september 1999 ; and on the eur / jpy market january 1999march 1999 , april 1999june 1999 , november 1999 , and july 2000december 2000 . these peaks mean that market participants offer quotes periodically and in synchronization . the possible reasons for these peaks to appear in the power spectrum densities of the market activity are follows : 1 . the market participants are affected by common periodic information . 2 . the market participants are spontaneously synchronized . in the next section the double - threshold agent model is introduced and explain this phenomenon on the basis of the reason ( 1 ) . here we consider a microscopic model for financial markets in order to explain the dependency of the peak height on observation periods . we develop the double - threshold agent model based on the threshold dynamics . in foreign exchange markets the market participants attend the markets with utilizing electrical communication devices , for example , telephones , telegrams , and computer networks . they are driven by both exogenous and endogenous information and determine their investment attitudes . since the information to motivate buying and one of selling are opposite to each other we assume that the information is a scaler variable . moreover the market participants perceive the information and determine their investment attitude based on the information . the simplest model of the market participant is an element with threshold dynamics . we consider a financial market consisting of @xmath4 market participants having three kinds of investment attitudes : buying , selling , and doing nothing . recently we developed an array of double - threshold noisy devices with a global feedback @xcite . applying this model to the financial market we construct three decision model with double thresholds and investigate the dependency of market behavior on an exogenous stimuli . the investment attitude of the @xmath5th dealer @xmath6 at time @xmath7 is determined by his / her recognition for the circumstances @xmath8 , where @xmath9 represents the investment environment , and @xmath10 the @xmath5th dealer s prediction from historical market data . @xmath6 is given by @xmath11 where @xmath12 and @xmath13 represent threshold values to determine buying attitude and selling attitude at time @xmath7 , respectively . @xmath14 is the uncertainty of the @xmath5th dealer s decision - making . for simplicity it is assumed to be sampled from an identical and independent gaussian distribution , @xmath15 where @xmath16 is a standard deviation of @xmath14 . of course this assumption can be weakened . namely we can extend the uncertainty in the case of non - gaussian noises and even correlated noises . the excess demand is given by the sum of investment attitudes over the market participants , @xmath17 which can be an order parameter . furthermore the market price @xmath18 moves to the direction to the excess demand @xmath19 where @xmath20 represents a liquidity constant and @xmath21 is a sampling period . @xmath22 may be regarded as an order parameter . the dealers determine their investment attitude based on exogenous factors ( fundamentals ) and endogenous factors ( market price changes ) . generally speaking , the prediction of the @xmath5th dealer @xmath10 is determined by a complicated strategy described as a function with respect to historical market prices , @xmath23 . following the takayasu s first order approximation @xcite we assume that @xmath10 is given by @xmath24 where @xmath25 is the @xmath5th dealer s response to the market price changes . it is assumed that the dealers response can be separated by common and individual factors , @xmath26 where @xmath27 denotes the common factor , and @xmath28 the individual factor . generally these factors are time - dependent and seem to be complicated functions of both exogenous and endogenous variables . for simplicity it is assumed that these factors vary rapidly in the limit manner . then this model becomes well - defined in the stochastic manner . we assume that @xmath27 and @xmath28 are sampled from the following identical and independent gaussian distributions , respectively : @xmath29 where @xmath30 represents a mean of @xmath27 , @xmath31 a standard deviation of @xmath27 , and @xmath32 a standard deviation of @xmath33 . since we regard the market activity as the number of tick quotes per unit time it should be defined as the sum of dealers actions : @xmath34 the market activity @xmath35 may be regarded as an order parameter . this agent model has nine model parameters . we fix @xmath36 , @xmath37 , @xmath38 , @xmath39 , @xmath40 , and @xmath41 throughout all numerical simulations . it is assumed that an exogenous periodic information to the market is subject to @xmath42 at @xmath43 , @xmath44 and @xmath45 . we calculate the signal - to - noise ratio ( snr ) of the market activity as a function of @xmath46 . the snr is defined as @xmath47 where @xmath48 represents a peak height of the power spectrum density , and @xmath4 noise level . from the numerical simulation we find non - monotonic dependency of the snr of @xmath35 on @xmath46 . [ fig : snr ] shows a relation between the snr and the noise strength @xmath46 . it has an extremal value around @xmath49 . namely the uncertainty of decision - making plays a constructive role to enhance information transmission . if there are exogenous periodic information and the uncertainty of decision - making we can find the peak on power spectrum densities at appropriate uncertainty of decision - making due to stochastic resonance @xcite . for the double - threshold agent model is plotted against the uncertainty of decision - making of agents at @xmath36 , @xmath37 , @xmath38 , @xmath39 , @xmath50 , @xmath41 , @xmath51 , @xmath43 , @xmath44 , and @xmath45 . ] we analyzed time series of the number of tick quotes ( market activity ) and found there are short - time periodicities in the time series . the existence and positions of these peaks of the power spectrum densities depend on foreign currency markets and observation periods . the power spectrum densities have a peak at 2.5 minutes on the usd / jpy market , 3 minutes on the eur / usd . there are some peaks at a few minutes on the jpy / eur . we developed the double - threshold agent model for financial markets where the agents choose three kinds of states and have feedback strategies to determine their decision affected by last price changes . from the numerical simulation we confirmed that the information transmission is enhanced due to stochastic resonance related to the uncertainty of decision - making of the market participants . we propose a hypothesis that the periodicities of the market activity can be observed due to stochastic resonance . appearance and disappearance of these peaks may be related to the efficiency of the markets . the efficiency market hypothesis @xcite says that prices reflect information . because quotes make prices tick frequency can reflect information . if the peaks of the power spectrum densities come from exogenous information then snr is related to the efficiency of the market . namely the market may be efficient when the peaks appear . the author thanks prof . t. munakata for stimulative discussions and useful comments . this work is partially supported by the japan society for the promotion of science , grant - in - aid for scientific research # 17760067 . 99 r.n . mantegna and h.e . stanley , an introduction to econophysics : correlations and complexity in finance , cambridge university press , cambridge ( 2000 ) . m.m . dacorogna , r. genay , u. mller , r.b . olsen and o.v . pictet , an introduction to high - frequency finance , academic press , san diego ( 2000 ) . t. mizuno , t. nakano , m. takayasu , and h. takayasu , physica a , * 344 * ( 2004 ) 330 . a .- h . sato and h. takayasu , physica a * 250 * ( 1998 ) 231 . t. lux and m. marchesi , nature , * 397 * ( 1999 ) 498500 . d. challet , m. marsili and yi - cheng zhang , physica a , * 294 * ( 2001 ) 514524 . p. jefferies , m.l . hart , p.m. hui and n.f . johnson , the european physical journal b , * 20 * ( 2001 ) 493501 . a. krawiecki and j.a . hoyst , physica a , * 317 * ( 2003 ) 597 . the data is provided by cqg international ltd . sato , k. takeuchi , and t. hada , physics letters a , * 346 * ( 2005 ) 27 . h. takayasu , and m. takayasu , physica a , * 269 * ( 1999 ) 24 . l. gammaitoni , p. hnggi , p. jung , and f. marchesoni , review of modern physics , * 70 * ( 1998 ) 223 . e. fama , journal of finance , * 46 * ( 1991 ) 1575 .

power spectrum densities for the number of tick quotes per minute ( market activity ) on three currency markets ( usd / jpy , eur / usd , and jpy / eur ) for periods from january 1999 to december 2000 are analyzed . we find some peaks on the power spectrum densities at a few minutes . we develop the double - threshold agent model and confirm that stochastic resonance occurs for the market activity of this model . we propose a hypothesis that the periodicities found on the power spectrum densities can be observed due to stochastic resonance . tick quotes , foreign currency market , power spectrum density , double - threshold agent model , stochastic resonance + * pacs * 89.65.gh , 87.15.ya , 02.50.-r

Egypt's Muslim Brotherhood vowed Thursday to continue its "peaceful" resistance in defiance of the military's ouster of the country's Islamist President Mohammed Morsi. Supporters of ousted Egypt's President Mohammed Morsi, hold his portraits and wave Egyptian flags as they shout slogans during a demonstration after the Iftar prayer, evening meal when Muslims break their... (Associated Press) Supporters of ousted Egypt's President Mohammed Morsi shout slogans during a demonstration after the Iftar prayer, evening meal when Muslims break their fast during the Islamic month of Ramadan, in Nasr... (Associated Press) Supporters of the ousted Egypt's President Mohammed Morsi, wave an Islamic group flag with Arabic words which read "No God but Allah and Mohammad is his prophet," during a demonstration after the Iftar... (Associated Press) A young girl holds a portrait of ousted Egypt's President Mohammed Morsi as she rides on her father's motorcycle during a demonstration after the Iftar prayer, evening meal when Muslims break their fast... (Associated Press) An injured Sheik, center, a supporter of ousted Egypt's President Mohammed Morsi, who was wounded on his eye during clashes with anti-Morsi protesters last week, attends the Tarawih prayer, after the... (Associated Press) Supporters of the ousted Egypt's President Mohammed Morsi, hold his portrait as they shout slogans during a demonstration after the Iftar prayer, evening meal when Muslims break their fast during the... (Associated Press) Supporters of the ousted Egypt's President Mohammed Morsi, hold his portrait during a demonstration after the Iftar prayer, evening meal when Muslims break their fast during the Islamic month of Ramadan,... (Associated Press) A supporter of ousted Egypt's President Mohammed Morsi, wears a mask that shows the face of Morsi during a demonstration after the Iftar prayer, evening meal when Muslims break their fast during the Islamic... (Associated Press) An Egyptian boy stands among the supporters of ousted Egypt's President Mohammed Morsi, who are offering the the Tarawih prayer, after the evening meal when Muslims break their fast during the Islamic... (Associated Press) A supporter of ousted Egypt's President Mohammed Morsi, cries during the Tarawih prayer, after the evening meal when Muslims break their fast during the Islamic month of Ramadan, in Nasr City, Cairo,... (Associated Press) A supporter of ousted Egypt's President Mohammed Morsi, wears a mask that shows the face of Morsi as he flashes victory sign, during a demonstration after the Iftar prayer, evening meal when Muslims break... (Associated Press) Supporters of the ousted Egypt's President Mohammed Morsi hold his portraits during a demonstration after the Iftar prayer, evening meal when Muslims break their fast during the Islamic month of Ramadan,... (Associated Press) Supporters of the ousted Egypt's President Mohammed Morsi, shout religious slogans during a demonstration after the Iftar prayer, evening meal when Muslims break their fast during the Islamic month of... (Associated Press) Supporters of the ousted Egypt's President Mohammed Morsi, shout pro-Morsi slogans as they hold a banner against Egyptian Defense Minister Gen. Abdel-Fattah el-Sissi, during a demonstration after the... (Associated Press) A Brotherhood statement also distanced the group from an assassination attempt Wednesday against a senior army commander in the Sinai Peninsula. The statement came a day after Egypt's military-backed government tightened its crackdown on the Brotherhood, ordering the arrest of its spiritual leader in a bid to choke off the group's campaign to reinstate Morsi, now held at an undisclosed Defense Ministry facility. "We will continue our peaceful resistance to the bloody military coup against constitutional legitimacy," the Brotherhood said. "We trust that the peaceful and popular will of the people shall triumph over force and oppression." Morsi was Egypt's first freely elected president. He was ousted by the military on July 3, following a wave of protests by millions of Egyptians who took to the streets to call for his removal. The Brotherhood's statement also denounced the assassination attempt against Maj. Gen. Ahmed Wasfi in the Sinai town of Rafah, near the border with Gaza, saying the group adheres to peaceful measures in line with what it says are the teachings of Islam. The Brotherhood denounced the warrants for the arrest of Mohammed Badie and nine other leading Islamists for inciting violence that left dozens dead in Cairo on Monday, saying "dictatorship is back" and insisting it will never work with the interim rulers. Leaders of the Brotherhood are believed to be taking refuge somewhere near a continuing sit-in by the group's supporters at the Rabaah al-Adawiya Mosque in eastern Cairo, but it is not clear if Badie also is there. Security agencies have already jailed five leaders of the Brotherhood, including Badie's powerful deputy, Khairat el-Shaiter, and shut down its media outlets. The prosecutor general's office said Badie, another deputy, Mahmoud Ezzat, senior member Mohammed El-Beltagy and popular preacher Safwat Hegazy are suspected of instigating Monday's clashes with security forces outside a Republican Guard building that killed 54 people _ most of them Morsi supporters _ in the worst bloodshed since he was ousted. The Islamists have accused the troops of gunning down protesters, while the military blamed armed backers of Morsi for attempting to storm a military building. The arrest warrants highlight the armed forces' zero-tolerance policy toward the Brotherhood, which was banned under authoritarian leader Hosni Mubarak. "This just signals that dictatorship is back," said Brotherhood spokesman Ahmed Aref. "We are returning to what is worse than Mubarak's regime, which wouldn't dare to issue an arrest warrant of the general leader of the Muslim Brotherhood." The Brotherhood's refusal to work with the new interim leaders underscored the difficulties they face in trying to stabilize Egypt and bridge the deep fissures that have opened in the country during Morsi's year in office. ||||| Image copyright Getty Images Image caption The removal of President Morsi sent a very dangerous message to Islamists Even posing that question will annoy many. Away from the troublespots, life for millions of Egyptians continues as normal. Egypt's most fundamental problems are more economic than political. But in a week when the political arm of the Muslim Brotherhood called for "an uprising by the great people of Egypt against those trying to steal their revolution with tanks", when dozens were killed in clashes between the army and Islamists and when the grand sheikh of al-Azhar warned of a civil war, an awkward question hovers in the air. Is Egypt now prone to a new "holy war" fought by Islamists against the authorities? Extremist minority There are plenty of grounds for optimism that the Arab world's most populous country should be able to avoid a descent into wide-scale, fanatical, religiously-inspired violence following the ousting of President Mohammed Morsi last year. The threat to Egypt only becomes real when such rhetoric inspires people to translate it into violent action Having lived there twice, for several years, I have experienced first-hand how good-natured, generous and mostly tolerant Egyptians can be. There are extremists in their midst but they are in a minority. Their views, however noisily they are broadcast, do not represent the bulk of the population. Egypt has also survived worse crises within living memory: the assassination of its president by a jihadist cell in 1981 and an Islamist insurgency that killed more than 700 people in the late 1990s, culminating in the massacre of 58 foreign tourists at Luxor in 1997. But given the unhappy confluence of events and trends surfacing in Egypt this week, it would be unwise to ignore the seeds of a potential holy war now being sown. Let's look at the ingredients: 'Martyrdom', banners and rhetoric "We will carry out explosions, we will shoulder arms, and nothing other than death will dissuade us from restoring President Morsi to the palace," the newspaper, al-Hayat, quoted a bearded man proclaiming at one of the sit-ins by Muslim Brotherhood supporters. Image copyright Reuters Image caption A blood-stained Egyptian flag was flown at a Muslim Brotherhood protest in Cairo Small numbers of young men are starting to be seen in the crowd wearing the white shrouds of "martyrdom", a theatrical show of how far some say they are prepared to go to return an elected Islamist president to power. Since Mr Morsi's removal, some internet forums have erupted with angry calls for vengeance against Egypt's military, calling it "the enemy of Islam" and declaring police and soldiers to be targets for attack, as they were in southern Egypt during the insurgency of the 1990s. For now, these statements are mostly rhetorical and aspirational - although security forces have often been attacked in the Sinai. The threat to mainland Egypt only becomes real when such rhetoric inspires people to translate it into violent action. Available weapons Security in Egypt has deteriorated dramatically since the overthrow of the dictatorial President Hosni Mubarak in 2011, but compared with Syria, Libya, Iraq and Yemen there are still relatively few firearms in private hands. Image copyright Reuters Image caption The Muslim Brotherhood is demanding the military reinstate Mr Morsi as president Yet mainland Egypt is sandwiched between two land masses awash with illegal weapons: Libya and the Sinai peninsula. The overthrow of Col Muammar Gaddafi's regime next-door in Libya threw open the doors to his armouries, releasing a flood of firearms, many of which have ended up with jihadist groups operating across the Sahara and in eastern Libya. A UN report published in April concluded that "weapons used during the Libyan civil war against Muammar Gaddafi are being funnelled at an alarming rate to other countries in the region". It said the weapons ranged from small arms to high-powered explosives, mines and portable air-defence systems. The report said this flow of weapons into Egypt was a threat to its internal security because many were reaching anti-government insurgents in Sinai. Religious clashes Nearly 10% of Egypt's population are Coptic Christians. Image copyright AP Image caption There were clashes between Christians and Muslims in Egypt during Mr Morsi's rule Mostly, they live harmoniously in this Muslim-majority country but some Islamist extremists want to see them driven out, as much of Iraq's Christian population has been. There have been isolated but deadly attacks on Egypt's churches and Christians, and for the past year during Mr Morsi's presidency, many Egyptian Copts doubted his government's commitment to protect their community properly. Now that he has been ousted, there is a counter-suspicion by some Muslim Brotherhood supporters that Christians somehow had a hand in his removal. If Egypt were to fall prey to jihadist violence, then its Coptic Christians would find themselves easy targets. Political frustration The military coup will certainly lead to serving extremist groups within the Islamic current Abdel Bari Atwan, al-Quds al-Arabi There is an almost unanimous view amongst analysts of the Middle East that, however incompetent the rule of President Morsi was, his forced removal after just one year in office sends a very dangerous message to Islamists. It risks leaving them with the conclusion that the democratic process the West has touted for so long is an avenue closed to them, prompting some to turn to the bullet instead of the ballot. Writing in al-Quds al-Arabi, the editor Abdel Bari Atwan said: "The military coup will certainly lead to serving extremist groups within the Islamic current, specifically within the Muslim Brotherhood, and will confirm the argument of al-Qaeda and other groups, which reject democracy and consider it a Western invention." Failing economy Lastly, but no less importantly, Egypt is facing a slow-motion economic crisis. Image copyright AFP Image caption Egypt's battered economy remains in crisis Since the 2011 uprising against Mr Mubarak, the country's latent economic and fiscal problems have gone into free fall. Tourism has slumped, unemployment and crime has soared, confidence has evaporated and the government is running out of money. Mr Morsi's inability to fix these problems was a major contributor to his unpopularity but those problems will still be there for whoever becomes his elected successor. A combination of a failing economy, zero job prospects and profound political frustration can lead to a dangerous sense of despair. Fertile ground, then, for those looking to recruit for nefarious purposes. You can follow Frank on Twitter @FrankRGardner Mardell: When is a coup not a coup? Bowen: Egypt's failed democratic experiment Q&A: Egypt in turmoil Key players in the Egyptian crisis ||||| CAIRO — They called it Egypt's largest-ever iftar table. Tens of thousands of supporters of ousted Islamist President Mohamed Morsi sat on a patchwork of blue tarps and carpets Wednesday evening, stretching block after block for nearly half a mile on the streets of Cairo's Rabaa district. After they fasted throughout the day in a sweltering tent encampment, anticipation built as dusk approached on Egypt's first day of Ramadan and crowds prepared to share iftar, the traditional evening meal when Muslims break their daily fast. Colorful streamers were hastily draped from tent to tent. Trucks distributed free food, including bags filled with cumin-spiced meat, dates, rice, tomatoes and beans for the moment the fast was declared over. A burst of fireworks signaled the time for prayer, and for a moment people in the crowd — who have been holding boisterous protests for more than a week to demand Morsi's reinstatement — were lost in religious meditation. But within seconds after the prayer concluded, the chanting resumed. "Morsi! Morsi! We give the power to God," they shouted, lifting pictures of the detained president. Only then did most families sit down to eat. Egypt entered its annual Ramadan season Wednesday with an overwhelming sense of national disunity. But if some were expecting that the monthlong period of fasting and reflection would provide some breathing space, Wednesday's mass iftar meal in Rabaa suggested that divisions might only be heightened during the period. Many, including the military that toppled Morsi last week, would like to see Ramadan sap the momentum from his Muslim Brotherhood supporters, who might find it hard to sustain protests while refraining from food and water from dawn to dusk. In most Muslim countries, daily life slows noticeably during Ramadan as people prefer to sleep during the day and spend the nights with family members and friends. And with the political turmoil, many Egyptians say they're not in a holiday mood this year. But if anything, the start of the holy month so far seems to be energizing Morsi's supporters, who vow to keep their sit-in alive even as they fast in temperatures that are expected to hit 100 degrees in the coming days. "This feels like a holy pilgrimage," said Eneyat Shenway, 38, a teacher and mother of five from the city of Mansoura. Doaa Ahmed, 33, from the Nile Delta, said her family usually prepares for Ramadan by decorating the house with colorful lanterns and cooking the children's favorite dishes, including grape leaves and basbousa, an Egyptian semolina cake. After eating, most Egyptians gather around the TV to watch popular miniseries, a Ramadan tradition here. This year Ahmed, her husband and their four young children had a simple meal of cheese sandwiches and juice boxes, sitting picnic-style on a plastic tarp in the street. "But this is better than any other Ramadan we've had," she said, adding that the holiday had special significance because of their struggle over Morsi's removal. Muslim Brotherhood officials said they were doing their best to create a holiday spirit in the encampment, decorating tents, laying carpets on the asphalt and planning nighttime soccer matches. "If anything, Ramadan is going to give strength to our cause," said Muslim Brotherhood cleric Gamal Abdel Sattar, a religious scholar at Al Azhar University. "Throughout history, Ramadan has been a time of victory for Muslims, so we are confident." Throughout the camp, people share a common view that God is on their side in the political struggle against secularists and liberals in the new interim government. They point to past examples of military victories for Muslims during the month of Ramadan, such as the initial successes during the 1973 Yom Kippur War against Israel. Engineer Reda Sayed, 45, described the political struggle in religious terms. "This is a secular crusade," he said. Still, because Ramadan is seen as a time of brotherhood, charity and equality, ardent Muslims might find it difficult to reconcile the holiday with anti-military protests or calls for vengeance. Harming or killing other Muslims is especially taboo. By the same token, the military might find itself more restrained during the holy month. Launching a crackdown against the protesters, such as the one Monday that killed at least 51 people, could trigger a public backlash. During Ramadan, it's not uncommon for violence and crime to drop, partly because people are physically weaker and more focused on religion. During the U.S. occupation of Iraq, for example, attacks against American troops usually dipped during Ramadan. A study in Saudi Arabia found men were less likely to beat their wives during the fasting month. Other research, however, suggests that fasting and giving up vices such as cigarettes can make people more irritable and intolerant. In 2009, a church burning in Egypt was attributed to the anti-Christian sentiments whipped up during Ramadan. During previous Palestinian uprisings, militant attacks against Israel's occupation often increased during Ramadan out of a belief that if a Muslim dies as a martyr during the holy month, the rewards in heaven are even greater. Most Muslim Brotherhood leaders have publicly called upon supporters to remain peaceful. But signs of militancy are evident in Rabaa. The neighborhood has been barricaded with brick walls where volunteer security guards, wearing motorcycle helmets and construction hats, stand at every entrance. Billy clubs and sticks are now sold on the streets with sunglasses and T-shirts. "Ramadan teaches us to be patient," said Abdel Hadi Mohamed, 30, a construction worker from Giza. "Even if we are attacked we won't strike back." Yet his pacifist words contrasted with the black club resting at his feet as he prepared to pray. Outside the camp, daily life in Cairo has returned to normal. But the growing polarization has put a damper on Egypt's usual vibrant Ramadan celebrations. Raed Mohamed, manager of El Basha supermarket, near the Rabaa sit-in, complained that his store is usually packed during the last 10 days before Ramadan. This year customers stayed away. He speculates that many are planning a low-key holiday or are afraid to come to his shop because of its proximity to the protests. "It just doesn't feel like Ramadan this year," he said. [email protected]

– Apart from all the political unrest and mass killings, Egypt has suddenly become a much better place to live—to a degree that the New York Times thinks is frankly suspicious. No sooner had Mohamed Morsi been ousted than the country's energy crisis seemed to vanish, with long lines at gas stations suddenly disappearing and power cuts ending. Police are back on the streets as well. Muslim Brotherhood supporters think the sudden turnaround is a sign that Mubarak-era personnel were sabotaging Morsi's Egypt. "This was preparing for the coup," a Morsi administration spokesman said. "Different circles in the state, from the storage facilities to the cars that transport petrol products to the gas stations, all participated in creating the crisis." Meanwhile: The Brotherhood disavowed involvement in an assassination attempt on a senior army commander, the AP reports. They vowed, however, to "continue our peaceful resistance to the bloody military coup." The unrest is all playing out against the backdrop of Ramadan, the LA Times points out. Tens of thousands of Morsi supporters gathered last night for a mass demonstration, a sign that the holy month will not dissipate the tensions. BBC correspondent Frank Gardner worries that all this could coalesce into a "holy war," as religious rhetoric flies, and guns seep in from Libya and the Sinai peninsula.

Story highlights "Sea lice," a.k.a. ocean itch or seabather's eruption, are actually microscopic marine larvae The larvae are as small as speck of pepper Their stings can cause itchy red rash and flu-like symptoms (CNN) Sea lice. Beach lice. Seabather's eruption. Pika-pika. Ocean itch. Those are just some of the names given to a rash caused by a minuscule creature that often invades summer waters in Florida and the Caribbean, pestering swimmers with nasty bumps and sometimes flu-like symptoms. As tiny as a speck of pepper or the period at the end of this sentence, sea lice are not lice at all but the microscopic larvae of marine life such as jellyfish and sea anemones. (Sea lice is also the name of a fish parasite that does not affect humans.) Sea lice are not lice at all by the microscopic larvae of marine life. According to the Florida Department of Public Health , "sea lice" have been infesting coastal waters for more than a century, with most of the outbreaks traced to larvae of the thimble jellyfish, Linuche unguiculata. Though visible to the naked eye, these baby jellies disappear from sight in the water, making them impossible to avoid. They tend to migrate inside bathing suits, making their way through the mesh of the fabric, where they become trapped and begin to sting. Unlike with the adult's sting, it doesn't hurt. You won't know you've been stung until the rash appears, usually within 24 hours, sometimes along with fever, chills, headaches and nausea. The rash is often raised, with bumps or blisters that can be very red and extremely itchy. Sea lice, also known as seabather's eruption, can cause an itchy rash. Read More ||||| Purple flags are popping up all over the Florida panhandle as a nearly-invisible nuisance is causing a headache for beach-goers. Sea lice, also known as beach lice, have been confirmed in South Walton and Santa Rosa Beaches, and they may be moving west towards Alabama. Sea lice are virtually impossible to see underwater, making them difficult to track. They are known to get stuck underneath bathing suits and irritate the skin, causing a rash known as seabather’s eruption. Rashes may include elevated skin with a reddish tint and some small blisters. Severe reactions can cause fever, chills, nausea and headache. News 5 has contacted officials in Orange Beach, who say they not heard any reports of sea lice on their beaches. Officials from Gulf Shores could not be reached. Experts say sea lice appear particularly in areas with warmer climates, such as the Gulf of Mexico and the Caribbean. Anyone in or near the affected areas with a raised purple flag is at risk. Officials say the best form of treatment is to rub the affected area with sand or the edge of a credit card and flush the skin with hot water. Your natural reaction may be to flush the affected area with cold water, but don’t – hot water is the key, experts say. Sea lice are the larvae of jellyfish and other ocean stingers that find their way onto shore in the currents. These microscopic larvae contain the same stinging cells as the adult creatures. Therefore, they sting – not bite. So far, there have been no reports of sea lice on Alabama’s beaches. ||||| Sea lice are popping up along Gulf Coast beaches. Sea lice, also known as beach lice, outbreaks have been reported mainly along the Florida panhandle. However, biologists say they expect to start seeing more sea lice move along the coastline to warmer waters, which means they could be headed to our area.Sea lice are virtually impossible to see underwater, making them difficult to track. They are known to get stuck underneath bathing suits and irritate the skin, causing a rash known as seabather's eruption.Rashes may include elevated skin with a reddish tint and some small blisters. Severe reactions can cause fever, chills, nausea and headache.Officials say the best form of treatment is to rub the affected area with sand or the edge of a credit card and flush the skin with hot water. Your natural reaction may be to flush the affected area with cold water, but don't - hot water is the key, experts say.Sea lice have been confirmed in Florida's South Walton and Santa Rosa Beaches. Experts say sea lice appear particularly in areas with warmer climates, such as the Gulf of Mexico and the Caribbean.While they can be found throughout the year, sea lice are most active from the months of April through August.To learn more about sea lice, visit FloridaHealth.gov ||||| Seabather's eruption is an itchy rash caused by a nearly invisible marine pest known as sea lice, which lurks in warm oceans, including the Gulf of Mexico and the Caribbean during the summer. Severe cases can result in flu-like symptoms. ABC station KTRK-TV of Houston has reported that sea lice outbreaks are on the rise this year, especially at beaches along the Gulf of Mexico. "Outbreaks of seabather's eruption occur intermittently between March and August, but they appear to peak during early April through early July," according to the Florida Department of Health. "Seabather's eruption appear to be caused by shifts in South Florida's currents, with the highest incidence of cases in such areas as Palm Beach County and Northern Broward County, where the Gulf Stream passes closest to shore." Sea lice are no bigger than a speck of ground pepper, according to the Florida DOH, and are the larvae of adult jellyfish. (What are commonly called sea lice are not the parasitic sea lice that plague farmed salmon and other saltwater fish.) The nearly invisible baby jellyfish get caught between swimmers' skin and their bathing suit, other clothes and even hair, making the larvae sting. According to Parks and Recreation officials for Palm Beach County, "Some people do experience a prickling sensation while in the water, though itching usually starts several hours after being in the water and lasts two to four days but can last as long as two weeks." Palm Beach County has posted sea lice signs to warn swimmers when there are outbreaks at its beaches. Other seaside Florida counties will hang purple flags at beaches to signal the presence of marine pests such as sea lice. The rash from sea lice, while a nuisance, often goes away on its own. The Florida DOH recommends treating the rash with an antihistamine or hydrocortisone cream. Bathing in colloidal oatmeal and applying calamine lotion can also help soothe the rash or itchiness. Beachgoers can avoid sea lice by wearing as little clothing as possible in the water. Changing out of bathing suits as soon as possible and washing bathing suits well can also help prevent severe bouts of seabather's eruption, according to the Florida DOH.

– The bathing suit areas of Florida swimmers are under attack by an invisible enemy: sea lice. ABC News reports experts expect to see widespread outbreaks of sea lice this summer, especially in the Gulf of Mexico. Sea lice are incredibly tiny jellyfish larvae that are invisible in the water. They get stuck between swimmers' skin and bathing suits or hair and start stinging. That leads to seabather's eruption—aka pika-pika or ocean itch, according to CNN. The itchy rash can last for two weeks. KTRK reports it can also cause chills, nausea, and fever. Authorities say the best way to avoid the rash is to wear as little clothing as possible while swimming. If you do get stung—you likely won't notice until a few hours later when the itching starts—rub the area with sand or a credit card's edge, then rinse with hot water. Swimmers in areas where sea lice are present should take off their swimsuits before showering and rinse them with vinegar or rubbing alcohol. Outbreaks of sea lice have already been confirmed in Florida, and the tiny creatures are possibly heading toward Alabama, WKRG reports.

an interesting feature of magnetic monopoles in gauge theories is that they can catalyse nucleon decay at strong interaction rate @xcite . the actual computation of the monopole catalysis cross section remains , however , an open problem . this computation would involve long - distance physics of two different kinds quark - monopole interactions and qcd phenomena and also short - distance physics responsible for baryon number non - conservation . most of the relevant effects are non - perturbative , and this makes even a semi - qualitative calculation difficult . an approach to this problem was suggested in ref . it was proposed to invoke the skyrme model of a nucleon @xcite which indeed works reasonably well in describing low energy properties of baryons @xcite . in the skyrme model , the nucleon is essentially a classical field theory object , a soliton . given that the t hooft polyakov monopole is also a soliton , the monopole - nucleon interactions are then possible to describe at the level of classical field theory . in the proposal of ref . @xcite , the monopole is treated as point - like . the non - conservation of baryon number comes in through the boundary condition imposed on the skyrme field at the monopole centre , i.e. , at the singularity . it is not entirely obvious whether concrete mechanisms of baryon number non - conservation indeed produce , in the limit of vanishing monopole size , the conjectured boundary condition . also , dealing with the singularity and the boundary condition imposed at the singularity may be inconvenient for numerical computations . one more complication inherent in the proposal of ref . @xcite stems from the fact that the spherically symmetric skyrme field in the monopole background corresponds to an electrically charged object ( `` proton '' ) , so one has to explicitly introduce leptons to make baryon number violation consistent with electric charge conservation . in this paper we present a simplified model where both monopole and skyrmion are smooth solutions of the classical field equations , the baryon number non - conservation is explicitly built in and is due to the classical analogue @xcite of the triangle anomaly , and there is no necessity to consider leptons . the price to pay is that the skyrme field in the presence of the monopole does not carry net electric charge , so our model mimicks the monopole catalysed decay of a neutron , rather than a proton . we shall concentrate on two aspects of our model . first , we study whether or not the baryon number non - conservation proceeds without suppression at the classical level . for this we shall have to consider a region near the monopole core . of course , it is not realistic to use the non - linear sigma model for describing physics near the core , but this step is inevitable in the classical calculation of monopole catalysis . by carrying out numerical analysis , we show that there are no states with non - zero baryon number on top of the t hooft polyakov monopole , irrespectively of the size of the monopole core , i.e. , monopole catalysis of nucleon decay indeed takes place . second , we find that the regime of `` point - like '' monopole sets in when the two scales , responsible for the sizes and masses of the monopole and skyrmion , respectively , are not yet widely different : our results are stable when the ratio of monopole and skyrmion sizes is below 0.03 , and the mass ratio is below 1 . this is a good sign for future numerical analysis of the skyrmion decay in skyrmion - monopole collisions . hence , our model may be a reasonable starting point for a semi - realistic calculation of the monopole catalysis cross section . this paper is organized as follows . we present our model in section 2 . to set the stage , we recapitulate the properties of the monopole and the skyrmion in section 3 . section 4 contains our main results , both analytical and numerical . we present concluding remarks in section 5 . to motivate our model , we recall first that the simplest theory incorporating skyrmions has @xmath0 global symmetry and contains the sigma field @xmath1 taking values in @xmath2 . we wish to introduce baryon number non - conservation through the classical anomaly in the baryonic current . the baryon number will be anomalous if @xmath3 or @xmath4 or both are gauged . the model should also possess magnetic monopoles ; if we do not extend the symmetry group , the monopoles are to be associated with the gauged ( part of ) @xmath0 . gauging @xmath3 alone is not sufficient : in that case the skyrme field would break the gauge group completely , no electromagnetic @xmath5 would be left unbroken , and there would be no magnetic monopoles . so , we come to fully gauged @xmath0 with gauge potentials @xmath6 @xmath7 realistic monopoles have very small sizes , so we have to break the non - abelian symmetry down to an abelian subgroup at a high energy scale . thus , we introduce two higgs triplets @xmath8 and @xmath9 in @xmath10 and @xmath11 representations , respectively . these break @xmath0 down to @xmath12 . the electromagnetic group is the vectorial subgroup of this @xmath12 , so we have to break axial @xmath5 at some point . for simplicity , we consider the minimal option , i.e. , we do not introduce extra higgs fields . then the axial @xmath5 is broken by the skyrme field itself . the existence of a relatively long - ranged axial gauge field is an unrealistic feature of our model ; however , in this paper we study the dynamics near the monopole core , so it will not be important whether or not the axial @xmath5 is truly long ranged . it is straightforward to extend our model by introducing yet another higgs field which would break the axial @xmath5 , but not the electromagnetic subgroup . to summarise , our model has @xmath0 gauge symmetry , with the skyrme field and two higgs fields in the following representations @xmath13 to simplify the calculations , we take the gauge couplings , higgs self - couplings and vacuum expectation values of the higgs fields the same in the left and right sectors , @xmath14 the action for this model is @xmath15 \nonumber \\ & - & \int~d^4x~\left [ \frac{1}{2 } \mbox{tr}(d_{\mu}\phi_a)^2 + \frac{1}{2 } \mbox{tr}(d_{\mu}\phi_b)^2 \right ] \nonumber \\ & - & \int~d^4x~\left [ \frac{\lambda}{8 } \left(\frac{1}{2 } \mbox{tr}(\phi_a^2 ) + v^2\right)^2 + \frac{{\lambda}}{8 } \left(\frac{1}{2}\mbox{tr}(\phi_b^2 ) + v^2\right)^2 \right ] \nonumber \\ & + & \int~d^4x~\left [ - \frac{f_{\pi}^2}{16 } \mbox{tr}(u^{\dagger } d_{\mu } u)^2 + \frac{1}{32e^2}\mbox{tr}([u^{\dagger}d_{\mu}u , u^{\dagger}d_{\nu}u]^2 ) \right ] \nonumber \\ & + & \gamma_{wzw } \label{action}\end{aligned}\ ] ] where @xmath16 and @xmath17 are the field strengths of @xmath18 and @xmath19 , the fields @xmath8 and @xmath9 are @xmath20 matrices from the algebras of @xmath3 and @xmath4 , respectively , @xmath21 \nonumber \\ d_{\mu } \phi_b & = & \partial_{\mu}\phi_b + [ b_{\mu } , \phi_b]\end{aligned}\ ] ] and @xmath22 and @xmath23 are the pion decay constant and the skyrme constant , respectively . the last term in eq . ( [ action ] ) is introduced to reflect anomalies @xcite . unlike in ref . @xcite , this term has almost no effect in our model . in most of this paper we neglect this term , and discuss its effect towards the end . in complete analogy to refs . @xcite , the gauge - invariant baryonic current is @xmath24 in the absence of the gauge fields , @xmath25 , this current reduces to the topological current , @xmath26 while in the presence of gauge fields it has an anomaly , @xmath27 thus , topologically non - trivial gauge fields lead to the non - conservation of baryon number ; in particular , they can unwind the skyrmion ( cf . refs . if it were not for the skyrme field @xmath28 , the left and right sectors of this model would decouple , the model would reduce to two identical copies of the georgi glashow @xmath2 model and there would exist two types of t hooft polyakov monopoles . in the presence of the skyrme field , the axial @xmath5 is broken , and there exists only one type of monopole . the monopole solution with zero baryon number has @xmath29 everywhere in space , whereas @xmath30 , @xmath31 are precisely the monopole fields of the georgi glashow model . the monopole size is determined by the mass of the vector bosons ; at @xmath32 one has @xmath33 , so that @xmath34 at large @xmath35 , the monopole mass is twice the mass of the @xmath2 monopole , i.e. , @xmath36 where the numerical constant @xmath37 depends slightly on @xmath38 and at @xmath39 is equal to @xcite @xmath40 the estimates ( [ 12 * ] ) , and ( [ 12 * * ] ) and ( [ 12 + ] ) will serve as reference points for our study of the monopole skyrmion system . in the regime of weak gauge coupling , the model possesses the skyrmion . once the gauge fields are ignored , this is the standard skyrmion of the @xmath2 sigma model . its radius , as defined in ref . @xcite , is @xmath41 and its mass is equal to @xmath42 to mimic the situation existing in grand unified theories , in what follows we shall mostly consider the range of parameters in which the ratios @xmath43 and @xmath44 are small . our main purpose is to consider configurations with non - vanishing baryon number sitting on top of the monopole . we shall see that the baryon number need not be integer , and that there are no static classical solutions with non - zero baryon number . the strategy to deal with such a situation is standard @xcite : we shall impose a constraint ensuring that the baryon number takes on a non - vanishing value , find a static classical solution of the constrained system and study the behaviour of energy as a function of the baryon number . we shall seek spherically symmetric solutions of the constrained system . to write down the ansatz , we note that the action ( [ action ] ) is invariant under the spatial reflection , @xmath45 , @xmath46 supplemented by the interchange of the left and right @xmath2 , i.e. , @xmath47 in the case of static fields with @xmath48 , the most general spherically symmetric ansatz consistent with this discrete symmetry ) . we have found , however , that the solutions always have this symmetry . ] is @xmath49 \nonumber \\ b_i & = & -{i\over 2 } \left [ \left ( \frac{a_1 ( r)-1}{r}\right)\varepsilon_{ijk}\sigma_j \hat x_k -\left ( \frac{a_2 ( r)}{r } \right ) ( \sigma_i -\hat x_i \hat x \cdot \vec \sigma ) -\left ( \frac{a_3 ( r)}{r } \right ) \hat x_i \hat x \cdot \vec \sigma \right]\ : \nonumber \\ \phi_a & = & \phi_b = i v h(r ) \hat x \cdot \vec \sigma \nonumber \\ u&=&\cos f(r ) + i\hat x \cdot \vec \sigma \sin f(r ) \label{6m**}\end{aligned}\ ] ] where @xmath50 is the unit radius - vector . with this ansatz , regularity of the skyrme field at the origin requires that @xmath51 is an integer multiple of @xmath52 ; without loss of generality we set @xmath53 other conditions , ensuring that the fields are regular at the origin , are @xmath54 it is convenient to introduce the dimensionless coordinate , @xmath55 with this coordinate , the distances are measured essentially in units of the size of the monopole core . the static energy functional is then written as follows ( neglecting the wzw term in eq . ( [ action ] ) ) @xmath56 @xmath57 \nonumber \\ & + & 2 \left[\rho^2 ( h')^2 + 2 ( a_1 ^ 2 + a_2 ^ 2 ) h^2 + \frac{{\lambda}}{4g^2 } \rho^2(h^2 - 1)^2\right]\nonumber \\ & + & \kappa_1 ( x^2 + 2y^2 ) + \frac{4\kappa_2}{\rho^2 } y^2 ( 2x^2 + y^2 ) \label{energyrad}\end{aligned}\ ] ] where the prime denotes the derivative with respect to @xmath58 , @xmath59 and we introduced the dimensionless parameters @xmath60 it is worth noting that in terms of these parameters , the ratios of the sizes and masses of the monopole and skyrmion , as given by eqs . ( [ 12 * ] ) ( [ vv ] ) , are expressed as @xmath61 where we take @xmath62 for definiteness . these ratios must be small in the limit of point - like monopole . the energy functional ( [ energyrad ] ) is still invariant under radial gauge transformations which shift @xmath63 and @xmath64 , @xmath65 and rotate @xmath66 . this gauge symmetry is the remnant of the axial @xmath5 ( we have fixed the vectorial @xmath5 by imposing the symmetry ( [ discretesymmetry ] ) ) . we shall fix the remaining gauge freedom shortly . it follows immediately from eqs . ( [ energyrad ] ) and ( [ defxy ] ) that in the absence of the monopole , i.e. , when @xmath67 , @xmath68 , the convergence of the term proportional to @xmath69 in the energy integral requires that @xmath70 is an integer multiple of @xmath52 . this means that the winding number of the skyrme field is integer , and hence is conserved . on the other hand , in the presence of the monopole , one has @xmath71 , and the convergence of energy does not impose any constraints on @xmath70 . in the presence of the monopole , the winding number of the skyrme field is arbitary . for spherically symmetric fields , the gauge - invariant baryon number takes the form @xmath72 @xmath73 \nonumber \\ & + & \frac{1}{\pi } \left[(a_1a_2 ' - a_1 ' a_2 ) - \frac{a_3}{\rho } ( a_1 ^ 2 + a_2 ^ 2 -1 ) \right ] \label{bnumber}\end{aligned}\ ] ] like the winding number of the skyrme field , the baryon number too need not be integer . to consider configurations with non - vanishing baryon number , it would seem natural to impose a constraint involving the baryon number , e.g. , @xmath74 however , we have chosen a slightly different constraint which simplifies the equations . we note first that one of the euler lagrange equations following from eq . ( [ energyrad ] ) does not contain the second derivatives . this equation is @xmath75 in fact , this equation is not completely independent : its derivative with respect to @xmath58 is a consequence of the other euler lagrange equations ( this is analogous to the time derivative of gauss law ) . if @xmath76 is zero at one value of @xmath58 , then it is zero everywhere , provided the second - order euler lagrange equations are satisfied . the idea is to impose a constraint which would modify the resulting equations in such a way that the left hand side of eq . ( [ dhda3 ] ) be allowed to be a non - vanishing constant , while the second order equations remain intact . the suitable form of this constraint is @xmath77 indeed , upon adding this constraint with the lagrange multiplier @xmath78 to the hamiltonian ( [ energyrad ] ) , one finds that the only change in the resulting equations is that eq . ( [ dhda3 ] ) now becomes @xmath79 the procedure is then to disregard the latter equation altogether , solve the original second order euler lagrange equations and find @xmath78 from eq . ( [ dhda3l ] ) ( the last step is actually unnecessary ) . we note that the constraint ( [ 42 + ] ) is invariant under gauge transformations ( [ restgauge ] ) . in fact , this constraint can be written in fully gauge - invariant form , since @xmath80 note also that the expression on the left hand side of eq . ( [ 42 + ] ) coincides with the expression for the baryon number , eq . ( [ bnumber ] ) , except for terms in the latter containing @xmath81 and @xmath82 . this indicates that the constraint ( [ 42 + ] ) should give rise to non - vanishing baryon number ( indeed , we shall see below that the integral ( [ 42 + ] ) approximates the baryon number very well ) . the fact that one no longer has to consider the variations of @xmath83 simplifies the analysis considerably . we can now impose the gauge condition @xmath84 directly in the hamiltonian . thus , the problem reduces to solving the euler lagrange equations following from the functional @xmath85 @xmath86 \nonumber \\ & + & 2 \left[\rho^2 ( h')^2 + 2 ( a_1 ^ 2 + a_2 ^ 2 ) h^2 + \frac{{\lambda}}{4g^2 } \rho^2(h^2 - 1)^2\right]\nonumber \\ & + & \kappa_1 ( \rho^2 ( f')^2 + 2y^2 ) + \frac{4\kappa_2}{\rho^2 } y^2 ( 2\rho^2 ( f')^2 + y^2 ) \label{energyrad1}\end{aligned}\ ] ] where @xmath87 is defined in eq . ( [ defxy ] ) . all these equations are of second order ; their form is not very illuminating , and we do not reproduce all of them here . we only write down the equation which is obtained by varying @xmath88 with respect to @xmath89 , @xmath90 = 2 \left[\kappa_1 + 4\kappa_2 ( f')^2 + 4 \frac{\kappa_2}{\rho^2}y^2 \right ] ( a_1 \cos f + a_2 \sin f)y \label{a*}\ ] ] it is straightforward to see that @xmath81 and @xmath82 decay exponentially at large @xmath58 , @xmath91 hence , away from the monopole core , equation ( [ a * ] ) becomes @xmath92 and its solution is @xmath93 where @xmath94 and @xmath95 are constants . in fact , only the asymptotic value @xmath94 is a free parameter ( for given @xmath96 and @xmath97 ) , as the constant @xmath95 is a function of @xmath94 for the soultions of the complete system . thus , the system of euler lagrange equations , corresponding to the functional ( [ energyrad1 ] ) , admits a one - parameter family of solutions parametrized by the asymptotic value @xmath94 . the baryon number and the energy for the solutions are determined by @xmath94 . we have obtained these families of solutions numerically for various values of @xmath96 and @xmath97 and computed their energies and baryon numbers . we shall present our results for a fixed value of the higgs self - coupling , @xmath98 to a good accuracy the baryon number is a linear function of @xmath94 : according to eq.([bnumber ] ) , in the gauge @xmath99 we have @xmath100 the last integral here is small ; we shall discuss this property later on . our first result is that the energy is always a monotonic function of the baryon number . this is shown in fig . 1 for three sets of parameters @xmath101 . this means that there are no static solutions with non - vanishing baryon number on top of the monopole . we note that the third set of parameters , @xmath102 , @xmath103 corresponds to a very small size of the monopole core as compared to the skyrmion size , @xmath104 . it is natural to expect that in this case , the regime of `` point - like '' monopole is realized . let us discuss this in some detail , with the of purpose of estimating the range of parameters at which this regime sets in . the situation of interest is when the monopole is small and heavy , @xmath105 this situation occurs at small @xmath106 and @xmath107 , see eqs . ( [ rtor ] ) , ( [ mtom ] ) . in this case the monopole core is unaffected by the skyrme field , i.e. , the profiles of @xmath108 and @xmath109 coincide with the undistorted monopole profiles ( and hence are independent of the baryon number ) , whereas @xmath110 is small . the first two terms in eq . ( [ energyrad1 ] ) are then irrelevant , and the properties of the radial skyrme field @xmath89 are determined by the hamiltonian @xmath111 & = & 4\pi \frac{f_{\pi}}{\sqrt{512}e } \int~d\rho~ ( \tilde{\cal{e } } - \tilde{\cal{e}}_{mon})(\rho ) \nonumber \\ \tilde{\cal{e } } - \tilde{\cal{e}}_{mon } & = & \sqrt{\frac{\kappa_1}{\kappa_2 } } \left [ \rho^2 ( f')^2 + 2 y^2\right ] + 4 \sqrt{\frac{\kappa_2}{\kappa_1 } } \frac{y^2}{\rho^2 } \left [ 2 \rho^2 ( f')^2 + y^2\right ] \label{f+}\end{aligned}\ ] ] where we made use of eq . ( [ kappas ] ) . the fields @xmath81 and @xmath112 entering this expression are spectators ( they correspond to the undistorted monopole ) . this is what we mean by the regime of `` point - like '' monopole . in fact , the monopole is in some sense never point - like , as its core affects the asymptotics of the radial skyrme field ( this feature we shall discuss later on ) , so it is more appropriate to speak of a _ spectator monopole_. there are several properties of the _ spectator monopole _ regime that may be used to estimate the range of parameters at which it is actually realised : \(i ) the profiles of @xmath81 and @xmath112 must coincide with the undistorted monopole profiles ; \(ii ) the profile @xmath63 should depend on the _ ratio _ @xmath113 , and not on the overall magnitude of @xmath114 ; in particular , for fixed @xmath94 , the second asymptotic coefficient @xmath95 in eq . ( [ a * * ] ) should depend on @xmath106 only ( this follows from eq . ( [ f+ ] ) ) ; \(iii ) the baryon number should be equal to @xmath115 ( this follows from eq . ( [ bv * ] ) and @xmath116 ) ; \(iv ) the energy , referenced from the monopole mass and expressed in units of the skyrmion mass , must depend only on the baryon number and _ ratio _ @xmath113 , @xmath117 ( this again follows from eq . ( [ f+ ] ) ) . the properties ( ii ) ( iv ) are illustrated in figs . 2 4 . the property ( i ) is particularly useful for establishing at what values of @xmath96 ( i.e. , @xmath118 ) the spectator monopole regime sets in for given @xmath97 ( i.e. , for given @xmath119 ) . we present the corresponding plots in fig . 5 . figures 2 5 show that the spectator monopole regime sets in at fairly large @xmath96 and @xmath97 , as large as @xmath120 , @xmath103 . these values of parameters correspond to @xmath121 and @xmath122 . a `` point - like '' monopole need not be really very small and very heavy . let us now discuss how the asymptotics of the radial skyrme function , namely , the constant @xmath95 at given @xmath94 , depends on the properties of the monopole core in the spectator monopole regime . at small @xmath106 , the behaviour ( [ a * * ] ) terminates at @xmath123 where the monopole function @xmath81 is already exponentially decaying ( i.e. , somewhat outside the core ) . indeed , the term @xmath124 on the left hand side of eq . ( [ a * ] ) becomes comparable to @xmath125 at @xmath126 this implies that the regime ( [ a * * ] ) terminates when @xmath81 is small , and @xmath127 is larger than 1 . for a crude estimate we take into account this effect only , set @xmath128 on the left hand side and @xmath129 on the right hand side of eq . ( [ m * ] ) and obtain that the asymptotic regime ( [ a * * ] ) terminates at @xmath130 at this value of @xmath58 , the function @xmath63 should be reasonably close to its value at @xmath131 , i.e. , @xmath132 . hence @xmath133 that is latexmath:[\[c_f \sim \frac{1}{4 } ( \pi - f_{\infty } ) slower than logarithmically . this shows that @xmath95 depends on the ratio @xmath113 logarithmically . we confirmed this expectation by numerical calculations , though instead of the coefficient @xmath135 at @xmath136 , we obtained that in the spectator monopole regime @xmath137 thus , in terms of the physical coordinate @xmath138 , the radial skyrme function outside the core behaves as @xmath139 everywhere in space , except for a region close to the monopole core , the least energy configuration with given baryon number is the @xmath138-independent hedgehog field , @xmath140 , while @xmath141 changes from @xmath52 to @xmath94 near @xmath142 . a crude estimate for the energy of configurations with , say , @xmath143 is obtained by integrating the energy density , @xmath144 , over the region @xmath145 . one finds , using the asymptotics ( [ a * * ] ) @xmath146 i.e. , up to logarithms , @xmath147 hence , the skyrmion looses most of its mass when approaching the monopole . this is illustrated in fig . we note in passing that if the baryon number were conserved , there would exist skyrmion monopole bound states with binding energy almost equal to the mass of the skyrmion . this is in accord with refs . @xcite . let us now discuss the wess zumino witten term in the action , the last term in eq . ( [ action ] ) . in our context , its main effect is to generate charge densities induced by the skyrme and gauge fields @xcite . a suitable gauge for calculating this effect is @xmath148 . in this gauge , the wzw term is @xcite ( we write the terms which do not vanish in the @xmath2 case ) @xmath149 @xmath150\ ] ] where @xmath151 is an integer ( number of colours in qcd ) . a straigtforward calculation gives for general spherically symmetric fields @xmath152 @xmath153 + ( \tilde{a } \leftrightarrow \tilde{b})\ ] ] where @xmath154 , @xmath155 are the radial fields in the gauge @xmath148 ( in writing this formula we did not assume the symmetry ( [ discretesymmetry ] ) ; the field @xmath156 has the same form as @xmath157 in ( [ 6 m * * ] ) but with @xmath158 substituted for @xmath159 ) , and @xmath160 making use of the symmetry ( [ discretesymmetry ] ) , we find @xmath161 hence , the wzw term induces ( vectorial ) electric charge density in the vicinity of the monopole . we have to check that the coulomb self - interaction due to this effect does not spoil our previous analysis . let us estimate the coulomb energy , making use of the spectator monopole approximation . returning to the original gauge @xmath162 , and setting @xmath163 , we obtain @xmath164 the electric charge density is induced in the region where @xmath89 is substantially different from @xmath52 . this occurs near and above @xmath142 , where @xmath81 is small . making use of eq . ( [ m * ] ) we find that the total induced charge is , up to logarithms , @xmath165 ^ 2 \sim \frac{\kappa_1}{\kappa_2 } \sim \frac{e^2 f_{\pi}^2}{g^2v^2}\ ] ] since @xmath166 , up to logarithms , we obtain an estimate for the coulomb energy @xmath167 which is very small compared to eq . ( [ + * ] ) . hence , in our model , the skyrmion on top of the monopole is ( nearly ) neutral , and the coulomb energy is negligible . the wzw term in the action may be safely ignored . for fixed parameters of the model , @xmath96 and @xmath97 , we have constructed the family of constrained solutions along which the baryon number monotonically decreases to zero and energy monotonically decreases to the monopole mass . these solutions , however , have different behaviours of the skyrme field at spatial infinity , i.e. , different values of the radial skyrme function at @xmath168 . one may doubt that the system can actualy travel along this path in configuration space : in the gauge @xmath48 , the kinetic energy contains a term @xmath169 which diverges if @xmath94 changes in time . also , the baryonic current ( [ 8 ] ) has spatial components whose asymptotics at large @xmath138 ( again in the gauge @xmath170 ) are @xmath171 for @xmath172 , there is the baryonic flux at @xmath173 , @xmath174 this may seem to indicate that the bayon number leaks to spatial infinity . certainly , an evolution with infinite kinetic energy is impossible , so in the gauge @xmath48 the asymptotic value @xmath94 can not change in time . to see how , in this gauge , the system can travel along the path with varying baryon number ( say , leading from @xmath143 to @xmath175 ) , one has first to transform each constrained solution of our family to a gauge in which @xmath141 rapidly tends to zero as @xmath173 . according to eqs . ( [ restgauge ] ) , ( [ a * * ] ) , each configuration of the new family will have non - vanishing @xmath83 , so that at large @xmath58 @xmath176 because of gauge invariance , the baryon numbers and energies of old and new configurations will be the same . travelling along the new path in the configuration space does not cost infinite kinetic energy . indeed , in the gauge @xmath177 , the electric field at large @xmath138 behaves as @xmath178 and the integral of @xmath179 converges . also , the baryonic current ( [ q * ] ) vanishes as @xmath173 , so the baryon number does not leak to spatial infinity . it merely disappears . this work was carried out in the framework of projects sc/2000/020 and ic/2000/021 of enterprise - ireland . the work of v.r . has been supported in part by the council for presidential grants and state support of leading scientific schools , grant 00 - 15 - 96626 , rfbr grant 99 - 01 - 18410 and crdf grant ( award rp1 - 2103 ) . 99 v. a. rubakov , jetp lett . * 33 * ( 1981 ) 644 ; nucl . b * 203 * ( 1982 ) 311 . c. g. callan , phys . d * 25 * ( 1982 ) 2141 ; phys . d * 26 * ( 1982 ) 2058 ; nucl . b * 212 * ( 1983 ) 391 . c. g. callan and e. witten , nucl . b * 239 * ( 1984 ) 161 . t. h. r. skyrme , proc . a * 260 * ( 1961 ) 127 . g. s. adkins , c. r. nappi and e. witten , nucl . b * 228 * ( 1983 ) 552 . i. zahed and g. e. brown , phys . * c 142 * ( 1986 ) 1 . e. witten , nucl . b * 223 * ( 1983 ) 422 , 433 . e. dhoker and e. farhi , phys . lett . b * 134 * ( 1984 ) 86 ; nucl . b * 241 * ( 1984 ) 109 . v. rubakov , nucl . b * 256 * ( 1985 ) 509 . j. ambjorn and v. a. rubakov , nucl . b * 256 * ( 1985 ) 434 . e. b. bogomolnyi and m. s. marinov , sov . * 23 * ( 1976 ) 357 . i. affleck , nucl . b * 191 * ( 1981 ) 429 . t. akiba , h. kikuchi and t. yanagida , phys . d * 38 * ( 1988 ) 1937 . y. brihaye , b. kleihaus and d. h. tchrakian , j. math . * 40 * ( 1999 ) 1136 b. kleihaus , d. h. tchrakian and f. zimmerschied , j. math . * 41 * ( 2000 ) 816 j. goldstone and f. wilczek , phys . lett . * 47 * ( 1981 ) 986 . * fig 1 . * energy ( referenced from the monopole mass and expressed in units of the skyrmion mass ) versus baryon number for @xmath103 , and @xmath120 ( solid line ) @xmath180 , ( dashed line ) , @xmath181 ( dotted line ) . * figure 5 . * profiles of the functions @xmath81 , @xmath82 , @xmath112 and @xmath89 for @xmath189 and @xmath190 ( dotted line ) , @xmath191 ( dashed line ) , @xmath192 ( solid line ) . for @xmath193 the profiles of @xmath81 , @xmath82 and @xmath112 are indistinguishable and coincide with the undistorted monopole profiles . * figure 6 . * energy ( referenced from the monopole mass and expressed in units of the skyrmion mass ) for the configurations with baryon number @xmath143 as a function of @xmath96 for a fixed value of @xmath97 .

we present a simple model where a nucleon is treated as the skyrmion , both monopole and skyrmion are smooth solutions of the classical field equations , the baryon number non - conservation is explicitly built in and is due to the classical analogue of the triangle anomaly , and there is no necessity to consider leptons . we show by numerical analysis that there are no static classical solutions with non - zero baryon number on top of the monopole , i.e. , that the monopole catalysis of skyrmion decay indeed proceeds classically .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Safety and Accountability in Construction Act''. SEC. 2. HIGHWAY SAFETY. (a) Submission of Project Management Plans.--Section 106(a)(1) of title 23, United States Code, is amended by striking ``such'' and inserting ``the project management plan and such other''. (b) Independent Safety Reviews.-- (1) In general.--Chapter 4 of title 23, United States Code, is amended by adding at the end the following: ``Sec. 413. Independent safety reviews ``(a) In General.--Subject to subsection (b), the Secretary of Transportation (or the Secretary's designee) is authorized to contract with a qualified independent engineer to objectively analyze the planning, design, construction methods, and materials used to construct any highway project financed with Federal funds if the Secretary (or the Secretary's designee) determines that-- ``(1) the project may endanger public safety; ``(2) the planning, design, or construction of the project differs from the State's existing Project Management Plan; ``(3) the project is experiencing significant cost overruns; or ``(4) there is a reasonable basis for requiring a safety review of the project by an independent engineer. ``(b) Selection of Independent Engineer.-- ``(1) In general.--If the Secretary makes a determination under subsection (a), the Secretary shall select and hire an engineer to conduct the analysis described in subsection (a). ``(2) Qualifications.--The engineer selected under this subsection-- ``(A) shall be a registered professional engineer with a background in the appropriate engineering discipline; ``(B) shall have significant knowledge and experience in highway projects; and ``(C) may not have any prior association with the project to be reviewed or any affiliation with any project participant. ``(3) Notification requirement.--If an engineer is selected under this section, the Secretary shall notify-- ``(A) the members of Congress of the districts in which the project being reviewed is located; and ``(B) the Committee on Commerce, Science, and Transportation of the Senate; ``(C) the Committee on Environment and Public Works of the Senate; and ``(D) the Committee on Transportation and Infrastructure of the House of Representatives. ``(c) Access.-- ``(1) In general.--The transportation department of each State in which a highway project is being reviewed by an independent engineer selected under subsection (b), and any contractors involved in the project, shall provide the engineer with reasonable access to the plans, records, and construction sites of the project. ``(2) Contract provisions.--Beginning on the date of the enactment of this section, each contract relating to a highway project receiving Federal financial assistance shall explicitly-- ``(A) authorize the Secretary of Transportation to conduct a safety review in accordance with this section; and ``(B) require the parties to comply with paragraph (1). ``(d) Reports.-- ``(1) Analysis findings.--At the conclusion of the analysis described in subsection (a), the independent engineer shall submit a report containing the findings of such analysis to-- ``(A) the Secretary of Transportation; ``(B) the Inspector General of the Department of Transportation; ``(C) the Administrator of the Federal Highway Administration; and ``(D) the transportation department of the State in which the project is located. ``(2) Internal review.--The Inspector General of the Department of Transportation shall ensure compliance with the requirements under this section and shall submit a report describing such compliance to-- ``(A) the Secretary of Transportation; ``(B) the Administrator of the Federal Highway Administration; and ``(C) the appropriate congressional committees. ``(e) Authorization of Appropriations.--There are authorized to be appropriated $15,000,000 for each fiscal year to carry out this section.''. (2) Clerical amendment.--The table of sections in chapter 4 of title 23, United States Code, is amended by adding at the end the following: ``413. Independent safety reviews.''. SEC. 3. TUNNEL INSPECTIONS. (a) In General.--Section 151 of title 23, United States Code, is amended-- (1) in the section heading, by inserting ``and tunnel'' after ``bridge''; (2) in subsections (a) and (c), by inserting ``and Tunnel'' after ``Bridge'' each place it appears in the subsection headings; (3) by inserting ``and tunnel'' after ``bridge'' each place it appears; (4) by inserting ``and tunnels'' after ``bridges'' each place it appears; and (5) in subsection (d), by striking ``section 104(a), section 502, and section 144 of this title.'' and inserting ``sections 104(a), 144, and 502 for the bridge inspection program and sections 104(a) and 502 for the tunnel inspection program.''. (b) Surface Transportation Program.--Section 133(b)(1) of title 23, United States Code, is amended by inserting ``, tunnels (including safety inspections),'' after ``highways)''.

Safety and Accountability in Construction Act - Requires state transportation departments to submit project management plans for federal-aid highway projects to the Secretary of Transportation for approval. Authorizes the Secretary to contract with a qualified independent engineer to provide independent safety reviews of federally-financed highway projects if certain determinations are made. Requires the Secretary to establish a national tunnel inspection program (including national standards for the inspection of such tunnels). Authorizes states to obligate apportioned surface transportation program funds for: (1) the construction and repair of tunnels; and (2) tunnel safety inspections.

more than a half million newborns are estimated to die annually from serious neonatal infections , accounting for about 15% of all neonatal deaths globally ( 1 , 2 ) . around 75% of neonatal deaths occur during the first week of life , with most in the first 48 hours ( 3 ) . in populations with very high neonatal mortality , up to a half of neonatal deaths may have an infectious cause ( 4 , 5 ) . umbilical cord is an important gateway for infections , since it includes necrotic tissue . the umbilical cord infection developing subsequent to bacterial colonization is one of the outstanding reasons of newborn mortality and morbidity in underdeveloped and developing countries ( 6 - 10 ) . therefore , one of the most important practices in newborn care is umbilical cord care . umbilical cord and the surrounding tissue should be frequently checked for signs of skin infection ( 11 ) . proper skin care for newborn , keeping the umbilical cord clean and providing fast drying are crucial in the prevention of umbilical cord infections . the most suitable time for umbilical cord care in babies is bathing time ( 13 ) . however , there are different opinions about whether baby should be bathed until the umbilical cord falls off or which bathing method is preferred . traditionally , sponge bathing is preferred for daily routine care until the umbilical cord falls off , and tub bathing is preferred after the cord is fallen off ( 11 ) . the american academy of pediatrics stated that tub bathing performed before the separation of umbilical cord may leave the umbilical cord wet and predispose infection by delaying its separation ; thus , it is required to make sponge bathing until the umbilical cord falls off ( 14 ) . contrary to this view , tub bathing is recommended for term newborns in the guideline for newborn skin care , developed by the association of women s health , obstetric and neonatal nurses ( awhonn)/national association of neonatal nurses ( 15 ) . there were many studies evaluating the effect of different solutions such as antiseptic solutions , human milk , water ( 13 , 16 , 17 ) and factors of maternal and newborn ( 18 ) on the time of separation of umbilical cord and development of infection . while there are limited studies evaluating the effect of performed bathing method on the time of separation of the umbilical cord worldwide ( 19 - 21 ) , there are no studies performed in turkey . this study aimed to evaluate the effects of sponge and tub bathing methods on the time of separation of the umbilical cord in term babies in turkey . this quasi - experimental and randomized controlled study was performed on 100 healthy term newborn babies and their mothers at zonguldak maternity and children 's hospital in zonguldak between 14.03.2013 - 18.05.2013 . babies who were not born as a result of multiple and high risk pregnancies , whose mothers did not have a chronic - systemic disease , hepatitis , acquired immunodeficiency syndrome and genital infection , born between 38 - 42 weeks , not undergone any intervention such as forceps and vacuum extraction during the delivery , did not show an early membrane rupture , weighted above 2.500 kg , whose apgar scores were between 7 - 10 , did not have a congenital defect , did not have a dermatological problem , did not develop a physiological or pathological jaundice after delivery and were living in zonguldak city center . babies who were born as a result of multiple and high risk pregnancies , whose mothers had a chronic - systemic disease , hepatitis , acquired immunodeficiency syndrome and genital infection , born before 38 weeks , undergone interventions such as forceps and vacuum extraction during the delivery , showed an early membrane rupture , weighted below 2.500 kg , whose apgar scores were below 7 , had a congenital defect , had a dermatological problem , developed a physiological or pathological jaundice after delivery and were not living in zonguldak city center . the hospital is in zonguldak city center located in western black sea region of turkey . it is a governmental and specialized hospital , which provides maternity and pediatrics services and has 135 beds . in this study we wanted to reach all newborn babies and their mothers eligible for selection criteria and whose families agreed to participate in the study between 14.03.2013 and 18.05.2013 . in accordance with these criteria , 109 ( 56 sponge bathing , 53 tub bathing ) healthy term newborn babies and their mothers participated in the study . the study was completed on 100 babies and their mothers ( 49 sponge bathing , 51 tub bathing ) , because four of newborns were given phototherapy due to physiological jaundice during the study and five mothers of newborns did not agree to complete the study . descriptive characteristics data form was used for data collection by the researchers in accordance with the literature ( 18 ) . there were 20 questions within the form including descriptive information regarding mother , father and newborn , and 12 questions including information for mothers regarding umbilical cord and skin care and subject - oriented applications . these booklets prepared for sponge and tub bathing for newborn babies included the materials required for sponge and tub bathing , appropriate room temperature , place for bathing , appropriate time , how to give bath , order of bath , considerations for bathing , practice after bathing , cleaning of genital regions and umbilical cord care ( 70% alcohol was used in umbilical cord care in the both groups ) ( 11 , 12 ) . preliminary practice with descriptive characteristics data form and the booklets for sponge ( with 10 mothers ) and tub bathing ( with 10 mothers ) was performed by interviewing 20 mothers before starting the study . after preliminary practice , it was determined that descriptive characteristics data form was applicable and the booklets for sponge and tub bathing could be easily understood . family health center group detected mothers who were within 37th week of pregnancy in the family health centers and mothers were visited at their homes and informed about the study . the mothers who were willing to participate in the study were given descriptive characteristics data form and asked which bathing method they wanted to use after having information about both bathing methods . mothers were informed about the bathing method they have chosen and given a practice booklet at these visits . one of the researchers went to babies home and observed their umbilical cord at 2 , 4 , 6 , 8 , 10 , 12 , 14 and 16th days after delivery . she also observed any signs of umbilical cord infection during home visits including swelling , erythema , discharge and odor . mothers were told to refer to hospital if they observed any of these signs and given the contact details of the researchers . home visits were ended after the umbilical cord was fallen off . to conduct the study , written approval was received from administration of zonguldak maternity and children 's hospital ( b.10.1.tkh.4.67.n.67.0.01/127 ) . all mothers were informed about the purpose of study and the research process and an informed consent was taken from mothers who agreed to participate in the study . during the study , statistical analysis was performed using spss 18.0 software ( pasw statistics for windows , chicago : spss inc ) software ( vs 18.0 ) . compliance with normal distribution for numerical variables was assessed by shapiro - wilk test . in descriptive statistics , numerical data were expressed as mean standard deviation ( median , minimum - maximum ) and categorical data were expressed as numbers and percentages . the differences between the groups for categorical variables were assessed by chi - square test . since parametric test assumptions were not met , mann - whitney u test was used to compare the two groups for numerical variables . this quasi - experimental and randomized controlled study was performed on 100 healthy term newborn babies and their mothers at zonguldak maternity and children 's hospital in zonguldak between 14.03.2013 - 18.05.2013 . babies who were not born as a result of multiple and high risk pregnancies , whose mothers did not have a chronic - systemic disease , hepatitis , acquired immunodeficiency syndrome and genital infection , born between 38 - 42 weeks , not undergone any intervention such as forceps and vacuum extraction during the delivery , did not show an early membrane rupture , weighted above 2.500 kg , whose apgar scores were between 7 - 10 , did not have a congenital defect , did not have a dermatological problem , did not develop a physiological or pathological jaundice after delivery and were living in zonguldak city center . babies who were born as a result of multiple and high risk pregnancies , whose mothers had a chronic - systemic disease , hepatitis , acquired immunodeficiency syndrome and genital infection , born before 38 weeks , undergone interventions such as forceps and vacuum extraction during the delivery , showed an early membrane rupture , weighted below 2.500 kg , whose apgar scores were below 7 , had a congenital defect , had a dermatological problem , developed a physiological or pathological jaundice after delivery and were not living in zonguldak city center . babies who were not born as a result of multiple and high risk pregnancies , whose mothers did not have a chronic - systemic disease , hepatitis , acquired immunodeficiency syndrome and genital infection , born between 38 - 42 weeks , not undergone any intervention such as forceps and vacuum extraction during the delivery , did not show an early membrane rupture , weighted above 2.500 kg , whose apgar scores were between 7 - 10 , did not have a congenital defect , did not have a dermatological problem , did not develop a physiological or pathological jaundice after delivery and were living in zonguldak city center . babies who were born as a result of multiple and high risk pregnancies , whose mothers had a chronic - systemic disease , hepatitis , acquired immunodeficiency syndrome and genital infection , born before 38 weeks , undergone interventions such as forceps and vacuum extraction during the delivery , showed an early membrane rupture , weighted below 2.500 kg , whose apgar scores were below 7 , had a congenital defect , had a dermatological problem , developed a physiological or pathological jaundice after delivery and were not living in zonguldak city center . the hospital is in zonguldak city center located in western black sea region of turkey . it is a governmental and specialized hospital , which provides maternity and pediatrics services and has 135 beds . in this study we wanted to reach all newborn babies and their mothers eligible for selection criteria and whose families agreed to participate in the study between 14.03.2013 and 18.05.2013 . in accordance with these criteria , 109 ( 56 sponge bathing , 53 tub bathing ) healthy term newborn babies and their mothers participated in the study . the study was completed on 100 babies and their mothers ( 49 sponge bathing , 51 tub bathing ) , because four of newborns were given phototherapy due to physiological jaundice during the study and five mothers of newborns did not agree to complete the study . descriptive characteristics data form was used for data collection by the researchers in accordance with the literature ( 18 ) . there were 20 questions within the form including descriptive information regarding mother , father and newborn , and 12 questions including information for mothers regarding umbilical cord and skin care and subject - oriented applications . these booklets prepared for sponge and tub bathing for newborn babies included the materials required for sponge and tub bathing , appropriate room temperature , place for bathing , appropriate time , how to give bath , order of bath , considerations for bathing , practice after bathing , cleaning of genital regions and umbilical cord care ( 70% alcohol was used in umbilical cord care in the both groups ) ( 11 , 12 ) . preliminary practice with descriptive characteristics data form and the booklets for sponge ( with 10 mothers ) and tub bathing ( with 10 mothers ) was performed by interviewing 20 mothers before starting the study . after preliminary practice , it was determined that descriptive characteristics data form was applicable and the booklets for sponge and tub bathing could be easily understood . family health center group detected mothers who were within 37th week of pregnancy in the family health centers and mothers were visited at their homes and informed about the study . the mothers who were willing to participate in the study were given descriptive characteristics data form and asked which bathing method they wanted to use after having information about both bathing methods . mothers were informed about the bathing method they have chosen and given a practice booklet at these visits . one of the researchers went to babies home and observed their umbilical cord at 2 , 4 , 6 , 8 , 10 , 12 , 14 and 16th days after delivery . she also observed any signs of umbilical cord infection during home visits including swelling , erythema , discharge and odor . mothers were told to refer to hospital if they observed any of these signs and given the contact details of the researchers . to conduct the study , written approval was received from administration of zonguldak maternity and children 's hospital ( b.10.1.tkh.4.67.n.67.0.01/127 ) . all mothers were informed about the purpose of study and the research process and an informed consent was taken from mothers who agreed to participate in the study . during the study , statistical analysis was performed using spss 18.0 software ( pasw statistics for windows , chicago : spss inc ) software ( vs 18.0 ) . compliance with normal distribution for numerical variables numerical data were expressed as mean standard deviation ( median , minimum - maximum ) and categorical data were expressed as numbers and percentages . the differences between the groups for categorical variables were assessed by chi - square test . since parametric test assumptions were not met , mann - whitney u test was used to compare the two groups for numerical variables . in table 1 , it is observed that there was no statistically significant difference between the two groups for education level of mother and father , employment status of mothers , father s occupation , family type and heating mode of the house ( p > 0.05 ) . the time of separation of umbilical cord in babies who were given sponge bathing ( 6.1 1.4 ) was shorter compared to those given tub bathing ( 8.3 2.5 ) ( p < 0.005 ) . while no infection finding was found in 49 babies who were given sponge bathing , signs of discharge and erythema were seen in 2 of 51 babies ( 3.9% ) who were given tub bathing and directed to a health institution ( table 3 ) . data are presented as mean sd ( median , min - max ) . based on the bathing method , no statistically significant difference was found between the two groups for age of mother and father , age of mother at first and last pregnancy , number of children and baby s weight at birth ( p > 0.05 ) . when we compared gestational age , gender and mode of delivery based on bathing method , we could not find any statistically significant difference between the groups ( p > 0.05 ) ( table 2 ) . the purpose of this study was to evaluate the effect of sponge and tub bathing given to newborns on the time of separation of umbilical cord . it was based on the hypothesis that the time of separation of umbilical cord in babies given sponge bathing is shorter than those given tub bathing . the study was completed on 100 babies and their mothers , including 49 sponge and 51 tub bathing . in the study , sponge and tub bathing groups showed similarities for education level of mothers and fathers , their ages , employment status and occupations , family type , mode of heating in the house , mother s age at first and last pregnancy , number of children , weight of baby at birth , gestational age , gender and mode of delivery . our findings showed that the time of separation of umbilical cord in babies in the sponge bathing group was 6.1 1.4 ( 4 - 11 ) days and it was 8.3 2.5 ( 4 - 16 ) days for babies in tub bathing group . the time of separation of umbilical cord in babies who were given sponge bathing was shorter than those given tub bathing and the difference between the two groups was statistically significant . since tub bathing performed before the separation of umbilical cord might keep umbilical cord wet , it might delay its separation and increase the risk of infection during traditional daily routine care for newborns . it is necessary to prefer sponge bathing until the umbilical cord falls off and tub bathing after it falls off ( 11 ) . conducted a randomized controlled study in obstetrics and gynecology unit of a hospital in canada to compare the effects of traditional sponge and tub bathing methods on healing and infection of umbilical cord in healthy term babies . the study was performed on 102 healthy babies who were 37 weeks and more , and 2500 grams and more , and postpartum mothers who were physiologically and psychologically well . mothers and babies enrolled in the study were classified as experimental tub bathing group ( n = 51 ) and sponge bathing control group ( n = 51 ) . before the study , 33 nurses who were working in the unit were trained for bathing practice and evaluation of babies . healing of umbilical cord in babies was evaluated according to umbilical cord assessment scale . in case of infection development , when considering the umbilicus assessment scores for umbilical cord healing , no difference was found between the groups and no infection was observed ( 19 ) . in our study , it is believed that shorter time for the separation of umbilical cord in babies given sponge bathing was due to the fact that umbilical cord was not getting wet during sponge bathing . umbilical cord was getting wet in babies given tub bathing and mothers could not dry it properly . a local bad odor , erythema and discharge may occur around the umbilical cord of newborns due to development of infection , since it may remain wet and the separation of umbilical cord may be delayed ( 11 ) . in this study , signs of infection on the umbilicus of babies given sponge and tub bathing were assessed . while no infection finding was observed in 49 babies in the sponge bathing group , discharge and erythema were seen on the umbilical cord in 2 of 51 babies ( 3.9% ) in the tub bathing group . however , no statistical analysis was performed since the number was insufficient . in the studies by henningsson et al . on healthy term babies , there was no difference between babies given sponge and tub bathing for cord infection and bacterial colonization . in our study , infection signs such as discharge and erythema were probably due to the fact that umbilical cord remained wet in babies given tub bathing ( 19 - 21 ) . it was determined that the time of separation of umbilical cord in babies given sponge bathing was shorter than those given tub bathing , while no infection finding was found in 49 babies given sponge bathing , signs of discharge and erythema were seen in 2 of 51 babies ( 3.9% ) given tub bathing and were directed to a health institution . since wetting the umbilical cord during tub bathing delays the separation of umbilical cord , sponge bathing first , it was conducted on babies and their mothers who were only eligible for selection criteria , and may not be generalized to other babies and their mothers who were not eligible for selection criteria . second , the results of this study were generated from a health - care unit in turkey , and may not be generalized to other cultures or countries . despite these limitations , key findings of the study are of value for umbilical cord care for turkish culture . first , it was conducted on babies and their mothers who were only eligible for selection criteria , and may not be generalized to other babies and their mothers who were not eligible for selection criteria . second , the results of this study were generated from a health - care unit in turkey , and may not be generalized to other cultures or countries . despite these limitations , key findings of the study are of value for umbilical cord care for turkish culture .

background : umbilical cord infection developing subsequent to bacterial colonization is one of the outstanding reasons of newborn mortality and morbidity in underdeveloped and developing countriesobjectives : this study aimed to evaluate the influence of sponge and tub bathing methods on umbilical cord separation time in full term babies in turkey.patients and methods : this quasi - experimental and randomized controlled study was performed on 100 healthy term newborn babies and their mothers . one - hundred full - term babies ( 51 sponge bathing , 49 tub bathing ) born at a state hospital between 14.03.2013 and 18.05.2013 with gestational age of 38 - 42 weeks , weighing 2500 grams and above and met the selection criteria were included as the study sample . two booklets were prepared about sponge bathing and tub bathing . mothers were instructed about sponge bathing and tub bathing , umbilical cord care in prenatal and postnatal periods . the first postnatal visit was performed at the hospital . home visits and telephone calls were continued until the day of cord separation . number , percent , mean and standard deviation values , qui - square and mann - whitney u tests were used for data assessment.results:the time of separation of umbilical cord in babies who were given sponge bathing ( 6.1 1.4 ) was shorter compared to those given tub bathing ( 8.3 2.5 ) ( p < 0.005).conclusions : since wetting of umbilical cord during tub bathing delays the separation of umbilical cord , sponge bathing is recommended for newborns until the umbilical cord falls off .

LONDON (AP) — Britain's Mail on Sunday says it has uncovered a major royal security breach by using an inexpensive app to track Prince William's air rescue ambulance while it is in the air. The paper said the 2.99 pound ($4.65) app allowed it to keep close track of William as he flew in his capacity as a private pilot with East Anglian Air Ambulance in eastern England. It published photos claiming to show William's helicopter landing and of the prince himself. The paper said Sunday that William's helicopter flies at low altitude at a relatively slow speed. William's press office refused to comment on the report. The prince returned to work several weeks ago after paternity leave. ||||| A publicly available app which tracks air travel allows users to follow Prince William as he takes to the skies as an air ambulance pilot, it was claimed last night. There were warnings that ‘flightradar24’ app, which costs just £2.99 to download, could present a major security risk by providing precise details of his location. Reporters from the Mail On Sunday used the mobile phone software to see how the Prince could be tracked earlier this week and published photographs of him at work to show how the data had revealed where he had been. Military planes are concealed from the app’s users, but the same protection is not thought to be used for the air emergency services. The reporters said they received alerts every time his East Anglian Air Ambulance took off on a 999 call and landed. Dai Davies, the former head of the Met’s Royalty Protection Squad, told the newspaper: “This would give me cause for concern and solutions need to be found by those in charge of the Prince’s security. You always have to be aware of the advance of technology – which this illustrates – and the ability of these terrorist groups to think outside the box. You always, always have to be one step ahead.” Buckingham Palace and the Metropolitan police, which is responsible for royal protection, has not responded to the claims, nor have the app’s manufacturers. The Bond Aviation Group, which operates the East Anglian Air Ambulances, said it could not comment on security arrangements.

– No sooner has Prince William begun a new job than cheap technology is out to ruin it for him: British tabloid journalists say they were able to track the man who's second in line to the throne as he made flights in his air ambulance using an app that goes for $3.99, reports the Independent citing the report in the Mail on Sunday. Reporters downloaded the flight-tracking Flightradar24 app—which blocks military flights, though not private air ambulance flights, from users—and say they received alerts every time William took to the skies over eastern England, raising what officials are calling a serious security risk. Says a former head of the Royalty Protection Squad: "You always have to be aware of the advance of technology—which this illustrates—and the ability of these terrorist groups to think outside the box. You always, always have to be one step ahead." William's helicopter is relatively slow and low-flying, notes the AP. Royal reps had no comment.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Indian Tribal Detention Facility Reform Act of 2004''. SEC. 2. DEFINITIONS. Section 2 of the Indian Law Enforcement Reform Act (25 U.S.C. 2801) is amended to read as follows: ``SEC. 2. DEFINITIONS. ``In this Act: ``(1) Branch of criminal investigations.--The term `Branch of Criminal Investigations' means the entity the Secretary is required to establish within the Division of Law Enforcement Services under section 3(d)(1). ``(2) Branch of detention services.--The term `Branch of Detention Services' means the entity that the Secretary is required to establish within the Division of Law Enforcement Services under section 3(f)(1). ``(3) Bureau.--The term `Bureau' means the Bureau of Indian Affairs of the Department of the Interior. ``(4) Complementary facility.-- ``(A) In general.--The term `complementary facility' means a facility for the provision of additional or necessary services to detainees as a result of their being in custody. ``(B) Inclusion.--The term `complementary facility' includes a detoxification center, protective custody cell, shelter care facility, community treatment center, halfway house, or any similar facility. ``(5) Detainee.--The term `detainee' means an individual who is held in a detention facility for any period of time. ``(6) Detention facility.--The term `detention facility' means a facility for holding of individuals for correctional, intergovernmental, or other custodial purposes that is-- ``(A) operated by the Bureau; or ``(B) operated by an Indian tribe under the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450 et seq.). ``(7) Division of law enforcement services.--The term `Division of Law Enforcement Services' means the entity established within the Bureau under section 3(b). ``(8) Employee of the bureau.--The term `employee of the Bureau' includes an officer of the Bureau. ``(9) Enforcement of a law.--The term `enforcement of a law' includes the prevention, detection, and investigation of an offense and the detention or confinement of an offender. ``(10) Indian country.--The term `Indian country' has the meaning given the term in section 1151 of title 18, United States Code. ``(11) Indian tribe.--The term `Indian tribe' has the meaning given the term in section 201 of Public Law 90-284 (commonly known as the `Civil Rights Act of 1968') (25 U.S.C. 1301). ``(12) Offense.--The term `offense' means an offense against the United States, including a violation of a Federal regulation relating to part or all of Indian country. ``(13) Secretary.--The term `Secretary' means the Secretary of the Interior. ``(14) Serious incident.-- ``(A) In general.--The term `serious incident' means an occurrence, event, activity, or other incident that results in-- ``(i) a risk of harm or actual harm to an individual or the community; or ``(ii) serious damage to property. ``(B) Inclusion.--The term `serious incident' includes all incidents relating to detainee deaths or injuries, suicides, attempted suicides, escapes, and officer safety issues.''. SEC. 3. BRANCH OF DETENTION SERVICES. Section 3 of the Indian Law Enforcement Reform Act (25 U.S.C. 2802) is amended-- (1) in subsection (d)(4), by striking ``Area'' each place it appears and inserting ``Regional''; and (2) by adding at the end the following: ``(f) Branch of Detention Services.-- ``(1) Establishment.--The Secretary shall establish within the Division of Law Enforcement Services a separate Branch of Detention Services. ``(2) Duties.--The Branch of Detention Services-- ``(A) except as prohibited by other Federal law, shall be responsible for the detention, confinement, and corrections of offenders within Indian country; ``(B) shall not be primarily responsible for routine law enforcement, criminal investigations, or police operations in Indian country; and ``(C) under an interagency agreement between the Secretary and Attorney General and subject to such guidelines as the appropriate agencies or officials of the Department of Justice may adopt, may be responsible for temporarily detaining individuals for the purpose of Federal prosecution, immigration, or transportation, or any other detention purpose. ``(3) Regulations.--The Secretary shall promulgate regulations establishing a procedure for active cooperation and consultation of the detention services employees of the Branch of Detention Services assigned to an Indian reservation with the governmental, law enforcement, and detention officials of the Indian tribes located on the Indian reservation. ``(4) Personnel.-- ``(A) Supervision and direction.--Personnel of the Branch of Detention Services-- ``(i) shall be subject only to the supervision and direction of the law enforcement personnel or personnel of the Branch of Detention Services or of the Division, as the Secretary considers appropriate; and ``(ii) shall not be subject to the supervision of the Bureau Agency Superintendent or Bureau Regional Director. ``(B) Effect of paragraph.--Nothing in this paragraph-- ``(i) precludes cooperation, coordination, or consultation, as appropriate, with non-law enforcement Bureau personnel at the agency or regional level; or ``(ii) restricts the right of an Indian tribe to contract a detention program under the authority of the Indian Self-Determination and Education Assistance Act (25 U.S.C. 450 et seq.) or to maintain its own detention operations. ``(C) Reestablishment of authority.-- ``(i) Request.--After the date that is 1 year after the date of establishment of the Branch of Detention Services, any Indian tribe may, by resolution of the governing body of the Indian tribe, request the Secretary to reestablish authority over detention of members of the Indian tribe directly through the Agency Superintendent or Bureau Regional Office Director rather than through the Branch of Detention Services. ``(ii) Approval.--In the absence of good cause to the contrary, the Secretary, on receipt of a resolution under clause (i), shall reestablish the authority as requested by the Indian tribe.''. SEC. 4. FUNDING. Section 9 of the Indian Law Enforcement Reform Act (25 U.S.C. 2808) is amended-- (1) by striking the section heading and all that follows through ``Any expenses'' and inserting the following: ``SEC. 9. FUNDING. ``(a) In General.--Any expenses''; and (2) by adding at the end the following: ``(b) Availability.--Funds made available to carry out this Act shall remain available until expended.''. SEC. 5. DETENTION REFORM AND REVIEW. The Indian Law Enforcement Reform Act is amended by inserting after section 10 (25 U.S.C. 2809) the following: ``SEC. 10A. DETENTION REFORM. ``(a) Findings.--Congress finds that-- ``(1) there are 74 detention facilities in Indian country; ``(2) serious deficiencies in Indian country detention have arisen, including-- ``(A) poor facility conditions; ``(B) lack of staff training; ``(C) understaffing; and ``(D) lack of detention facility administration and other operational standards, or failure to comply with any such standards; ``(3) those deficiencies create a dangerous and potentially life-threatening situation for detainees and detention personnel; ``(4) the April 2004 interim report of the Inspector General of the Department of the Interior found that deaths, escapes, and assaults on correctional officers have occurred at several detention facilities in Indian country as a result of those deficiencies; ``(5) the Division of Law Enforcement Services has responsibility for both law enforcement and detention services, but no clear lines of authority for detention services; ``(6) existing Federal law does not provide clear lines of authority or standards for detention services in Indian country; and ``(7) clear authority and standards are needed to assist detention and law enforcement officials in-- ``(A) meeting the principal goals of Indian country law enforcement and detention; ``(B) protecting life and property; and ``(C) reducing crime and recidivism rates. ``(b) Reporting Protocols for Serious Incidents.-- ``(1) In general.--Not later than 270 days after the date of enactment of the Indian Tribal Detention Facility Reform Act of 2004, the Bureau shall develop and implement protocols to ensure that all serious incidents occurring at a detention facility are reported promptly through an established chain of command. ``(2) Reporting of escapes to law enforcement authorities.--The protocols shall ensure that each incident involving an escape of a detainee from a detention facility is reported immediately to the appropriate Federal, State, tribal, and local law enforcement authorities. ``(3) Preliminary inquiries into serious incidents.-- ``(A) In general.--The Division of Law Enforcement Services shall conduct a preliminary inquiry of any serious incident to determine whether a full investigation is warranted. ``(B) Findings.--All findings made in conducting preliminary inquiries under subparagraph (A) shall be reported to the Division of Law Enforcement Services and the Assistant Secretary of the Interior for Indian Affairs. ``(4) Detention facilities staffing review.--The Bureau shall-- ``(A) not later than 90 days after the date of enactment of the Indian Tribal Detention Facility Reform Act of 2004, conduct a review of the staffing needs at all detention facilities; and ``(B) update that review annually. ``(c) Regulations.--Not later than 1 year after the date of enactment of the Indian Tribal Detention Facility Reform Act of 2004, the Secretary, after consultation with the Attorney General, shall promulgate regulations to carry out subsections (a) and (b). ``(d) Detention Facilities Review.-- ``(1) In general.-- ``(A) Consultation.--Not later than 1 year after the date of enactment of the Indian Tribal Detention Facility Reform Act of 2004, in consultation with Indian tribes to the extent practicable, the Bureau shall complete an assessment of the physical conditions and needs of all detention facilities. ``(B) Report.--Not later than 15 months after the date of enactment of the Indian Tribal Detention Facility Reform Act of 2004, the Bureau shall-- ``(i) submit to the Committee on Indian Affairs and the Committee on Appropriations of the Senate and the Committee on Resources and the Committee on Appropriations of the House of Representatives a report that describes the results of the assessment under subparagraph (A); and ``(ii) make the report available to Indian tribal governments. ``(2) Data and methodologies.--In preparing the report under paragraph (1), the Bureau shall use-- ``(A) the existing Department of Justice Federal Bureau of Prisons formula for determining the condition and adequacy of Department of Justice detention facilities, including operational standards; ``(B) data relating to conditions at detention facilities that have previously been compiled, collected, or secured from any source derived, so long as the data are accurate, relevant, timely, and necessary to preparation of the report; and ``(C) the methodologies of the American Institute of Architects or other accredited and reputable architecture or engineering associations responsible for detention facility construction. ``(3) Contents.--The report shall include-- ``(A) a catalog of the condition of detention facilities that-- ``(i) identifies the existing detention and complementary facilities and any detention and complementary facilities that do not exist but are needed, taking into consideration-- ``(I) the size of a detention facility or complementary facility; ``(II) the number of detainees in a facility; ``(III) the age and condition of a facility; ``(IV) interjurisdictional detention needs; ``(V) staff needs; and ``(VI) prisoner isolation and transportation needs; ``(ii) establishes a routine maintenance schedule for each facility; ``(iii) identifies staffing and operational needs of existing and needed facilities; and ``(iv) provides specific cost estimates needed to repair, renovate, lease or construct any new, existing or additional detention facilities or complementary facilities; ``(B) a detailed plan to bring all detention facilities and complementary facilities into compliance with applicable standards that includes-- ``(i) detailed information on the status of each facility's compliance with the standards; ``(ii) specific cost estimates for meeting the standards at each facility; and ``(iii) specific timelines for bringing each facility into compliance with the standards; ``(C) an assessment of the feasibility of developing regional detention facilities, taking into consideration the factors identified in subparagraph (A)(i) and a comparison of costs and benefits of regional facilities versus individual tribal facilities; and ``(D) an assessment of the feasibility of tribal operation of the facilities identified under subparagraphs (A)(i) and (C) under the Indian Self- Determination and Education Assistance Act (25 U.S.C. 450 et seq.), including-- ``(i) any cost savings that would result from tribal rather than Federal operation of the facilities; and ``(ii) a comparison of costs and benefits arising from individual tribal operation versus contracting detention services with State or local facilities. ``(4) Effect of subsection.--Nothing in this subsection requires termination of the operations of any facility that fails to comply with standards described in subparagraph (B). ``(5) Authorization of appropriations.--There is authorized to be appropriated to carry out this subsection $500,000, to remain available until expended.''.

Indian Tribal Detention Facility Reform Act of 2004 - Amends the Indian Law Enforcement Reform Act with respect to the operation of tribal detention systems in American Indian communities. Directs the Secretary of the Interior to establish within the Division of Law Enforcement Services a separate Branch of Detention Services. Requires the Bureau of Indian Affairs (BIA) to develop and implement protocols for reporting on serious incidents, particularly escapes, to appropriate law enforcement authorities. Requires the Division of Law Enforcement Services to conduct a preliminary inquiry of any serious incident to determine whether a full investigation is warranted. Directs the BIA to complete an assessment of the physical conditions and needs of all detention facilities.

use of thoracic epidurals for intra- and post - operative analgesia for open abdominal surgeries has exponentially increased over the last decade . however , the conventional method , since its inception , has been dependent on anatomical surface landmarks and loss of resistance technique ( lor). commonly used blind technique can lead to dural penetration and more serious neurological injury especially at dorsal levels . though there have been attempts at technical refinement using ultrasound ( us ) to improve accuracy and reduce the incidence of inadvertent dural entry , this is still underutilised in routine practice . various clinical trials have compared the conventional method of identifying epidural space based on anatomical landmark with us imaging . first explored the use of pre - procedure us in thoracic epidural punctures and showed efficacy of thoracic spine us imaging in comparison to magnetic resonance imaging . the meticulous practice of us scanning for central neuraxial block has been well defined in literature . however , in comparison to lumbar spine , the anatomy of midthoracic level ( t5t8 ) makes imaging much more challenging . the positioning of spinous process with steep angulation , overlying laminae and close vicinity of the epidural space to the spinal cord increases impending neurological complications at mid - thoracic level . the efficacy of us imaging in determining the depth of epidural space has been extensively documented by comparing the ultrasound depth ( ud ) in various axes to the actual needle depth ( nd) in obstetric and non - obstetric populations . the authors of this study trust that this is the first study comparing the two axes of us imaging to identify the epidural space at dorsal level . this study was designed to compare the efficacy of us imaging in the transverse median ( tm ) and paramedian sagittal oblique ( pso ) planes in accurately predicting the depth to the epidural space and the point of needle insertion in thoracic epidural needle placement for open abdominal surgeries . our study was carried out after approval by the institutional ethics committee ( ec / tmc/11/13 ) , over a period of 1 year ( september 1 , 2014august 1 , 2015 ) . we recruited 32 patients ( 16 in each group ) , above 18 years of age , ranging from american society of anesthesiologists physical status ( asa - ps ) 13 posted for elective open abdominal surgeries . criteria for exclusion were spinal surgery , trauma or deformity , coagulopathy , sepsis and abnormal local skin condition . patients randomised to group i underwent us in the parasagittal oblique plane and those in group ii in the tm plane . the pre - puncture scans were done with a 2.05.5 mhz curved array probe ( logiq e portable us machine from ge healthcare , uk ) on patients in the sitting position with the upper back and neck flexed . premedication consisted of oral lorazepam ( 2 mg ) the night before surgery and again at 6 am on the day of surgery with sips of water . preprocedural us scanning in all the patients was performed by single anaesthesiologist with 8 years of experience in doing usg - guided epidurals . the initial step was localisation of the level at which anaesthesia was desired corresponding to the surgical incision . this was done starting caudally at the sacrum and moving cranially to identify the l5s1 interlaminar space and sequentially all the cranial levels in the pso view . to see the sonoantomy at the designated level , the transducer was placed 12 cm paramedian and tilted obliquely towards the midline in pso group and transversely in the plane of the intervertebral space in tm group . the image was saved to facilitate measurement of the skin to the inner aspect of posterior complex depth ( the ud of epidural space ) by an independent observer in pso and tm plane [ figures 1 and 2 ] . an interspace above or below was selected , when the image quality in the chosen dermatome appeared poor . image quality was rated as either good ( sharp visualisation with clear demarcation ) , fair ( visualised but with poor demarcation ) , or inconclusive ( structures not discernible ) . l1 , l2 laminae , lf - pd ligamentum flavum - posterior duramater complex , vb - vd vertebral body - ventral duramater complex ultrasound scanning in transverse median plane . ap articular process , tp transverse process , lf - pd ligamentum flavum - posterior duramater complex in us imaging , the ligamentum flavum , posterior duramater , and the epidural fat contained therein appear as a single hyperechoic line referred to as the posterior complex , as described by sahota et al . the anterior duramater , posterior longitudinal ligament and posterior vertebral body were identified as discrete structures . in both groups , once an optimum view was obtained , the image was saved , the transducer was stabilised and the midpoints of the upper and lower and the right and left borders of transducer were marked . the intersection of the resulting horizontal and vertical lines was the site chosen for puncture and catheter placement . the actual puncture and catheter placement was done by an anaesthesia registrar blinded to the ud . the direction of needle insertion was the same as that of the us probe which afforded the best view of the relevant anatomy in either group . the conventional lor technique was used to determine the skin to posterior complex depth and the needle was duly marked once this was felt . the nd was measured to the nearest millimetre from the tip to the point referred to earlier . the outcome measures were the precision of measurement of the skin to posterior complex depth in both the planes ( ud - pso and ud - tm ) as compared to the depth measured during actual needle insertion ( nd - pso and nd - tm ) as detailed above ( primary outcome ) and the accuracy of determining the insertion point as gauged by the number of reinsertions ( change of puncture site ) and needle redirections ( secondary outcome ) . statistical measures included mean , standard deviation ( sd ) and interquartile range ( 25 and 75 percentiles ) for continuous data and percentages for discrete variables . inter - group comparison of continuous variables was done using the two sample t - test and fisher exact test for discrete variables . correlation between the ud and actual nd was calculated and concordance correlation coefficient ( ccc ) was used to determine the degree of agreement between ud and nd in both the planes . the differences between actual nd and ud estimated depth were graphically plotted against the mean of nd and ud for each patient for both tm and pso planes ( bland altman analysis ) . ( copyright 2011 , sas institute inc . , cary , nc , usa ) software . the study group consisted of 32 patients of whom one patient from the tm group ( group ii ) was excluded in the final analysis due to technical issues during imaging . there were no statistical differences between the pso and the tm groups for age ( p = 0.64 ) , sex ( p = 0.85 ) , weight ( p = 0.54 ) , height ( p = 0.48 ) and body mass index distribution ( p = 0.76 ) [ table 1 ] . the mean ud was 3.64 ( sd : 0.72 ) cm in pso group , and 3.71(sd : 0.74 ) cm in tm group , while mean nd was 3.8 ( sd : 0.77 ) cm in pso group and 3.88 ( sd : 0.77 ) cm in tm group . the primary outcome , i.e. , the comparison between ud and nd , done using pearson correlation coefficient , was 0.99 in both pso and tm group , and the ccc was 0.93 ( 95% confidence interval [ 95% ci ] : 0.810.97 ) and 0.90 ( 95% ci : 0.740.96 ) in pso and tm groups respectively , which showed a strong positive association [ figure 3 ] . the 95% limits of agreement were 0.08 ( upper ) to 0.24 ( lower ) . total number of patients with redirections of epidural needle is 13 ( 81% ) in pso group and 8 ( 53% ) in tm group ( p = 0.13 ) and with reinsertions is 3 ( 18.75% ) in pso group and 0 ( 0% ) in tm group ( p = 0.22 ) . there was no significant difference in image quality in two groups [ table 3 ] . the mean pain score during procedure was 1.31 in pso group and 1.13 in tm group , which were comparable in both groups . the differences between actual needle depth and ultrasound depth ( y - axis ) estimated depth graphically plotted against the means of the needle depth and ultrasound depth for each patient ( x - axis ) for both transverse median and paramedian sagittal oblique planes ( bland altman analysis ) bland - altman analysis : actual needle depth versus estimated ultrasound depth characteristics of the ultrasound imaging and neuraxial procedures our results indicate that there is a high degree of conformity between the depth to the posterior complex estimated on us and the actual depth as measured on needle insertion . us can , therefore , be a useful adjunct during insertion of thoracic epidural catheters , particularly at dorsal levels . our data show that total number of redirections and reinsertions of epidural needle are higher in pso group as compared to tm group but due to limitations of sample size we could not draw definite conclusions regarding the difference between the two groups . higher number of redirections and reinsertions in pso group can be attributed to the fact that we could not reproduce the oblique angle of the us beam and match it with actual needle trajectory during needle insertion . furthermore , the difference could be a consequence of epidural puncture in the transverse plane being the more commonly used technique in routine practice . in our study , the actual nd is more than the us - estimated depth by a mean of 0.16 cm , which shows that us scan can likely guard against unintended dural puncture . thus lor testing along with us imaging go hand in hand to avoid evitable complications while performing the epidural block . the use of us in comparing the depth of epidural space to the actual nd and a good correlation of ud , with nd in different axes for obstetric and non - obstetric populations has been described in literature . we can compare our results with a similar study which showed a good association of the ud , and actual nd in pso plane at mid and low dorsal levels . another group compared two axes in obese pregnant women with us and both the pso and tm scan were performed at a single lumbar level in all patients , whereas our study group was heterogeneous and patients were randomised to either pso or tm group and the procedure was performed at the dorsal level . the limitations of our study are small sample size and the inability to direct the needle along a trajectory identical to that of the us beam . in addition , all scans were done by a single operator and therefore inter - rater variability at different levels of experience and proficiency could not be assessed . pre - puncture ultrasonographic estimates of the depth to the epidural space obtained in the pso plane are comparable to those obtained in the tm plane at thoracic level . larger studies with the incorporation of real - time sonography would be helpful in evaluating the potential advantages of pre - puncture us scanning .

background and aims : the use of ultrasound ( us ) scanning to assess the depth of epidural space to prevent neurological complications is established in current practice . in this study , we hypothesised that pre - puncture us scanning for estimating the depth of epidural space for thoracic epidurals is comparable between transverse median ( tm ) and paramedian sagittal oblique ( pso ) planes.methods:we performed pre - puncture us scanning in 32 patients , posted for open abdominal surgeries . the imaging was done to detect the depth of epidural space from skin ( ultrasound depth [ ud ] ) and needle insertion point , in parasagittal oblique plane in pso group and transverse median plane in tm group . subsequently , epidural space was localised through the predetermined insertion point by loss of resistance technique and needle depth ( nd ) to the epidural space was marked . correlation between the ud and actual nd was calculated and concordance correlation coefficient ( ccc ) was used to determine the degree of agreement between ud and nd in both the planes.results:the primary outcome , i.e. , the comparison between ud and nd , done using pearson correlation coefficient , was 0.99 in both pso and tm groups , and the ccc was 0.93 ( 95% confidence interval [ 95% ci ] : 0.810.97 ) and 0.90 ( 95% ci : 0.740.96 ) in pso and tm groups respectively , which shows a strong positive association between ud and nd in both groups.conclusion:the use of pre - puncture us scanning in both pso and tm planes for estimating the depth of epidural space at the level of mid- and lower - thoracic spine is comparable .

TAINAN, Taiwan Rescuers pulled two survivors from the rubble of a Taiwan apartment block on Monday more than 48 hours after it was toppled by an earthquake, but the mayor of the southern city of Tainan warned the death toll was likely to exceed 100. The official death toll from the quake rose to 38, with more than 100 people missing. The quake struck at about 4 a.m. on Saturday (2000 GMT Friday) at the beginning of the Lunar New Year holiday, with almost all the dead found in the toppled Wei-guan Golden Dragon Building in Tainan. Rescue efforts are focused on the wreckage of the 17-storey building, where 117 people are listed as missing and are suspected to be buried deep under the rubble. Wang Ting-yu, a legislator who represents the area, told reporters that a woman, identified as Tsao Wei-ling, was found lying under her dead husband. Their 2-year-old son, who was also killed, was found lying nearby. Another survivor, a man named Li Tsung-tian, was pulled out later on Monday, with Taiwan television stations showing live images of the rescues. Several hours later, Li's girlfriend was found dead in the rubble. Tainan Mayor William Lai said during a visit to a funeral home that rescue efforts had entered what he called the "third stage". "There are more fatalities than those pulled out (alive), and the number of fatalities will probably exceed 100," Lai said in comments carried on the United Daily News website. Rescuers continued to scramble over the twisted wreckage of the building as numbed family members stood around, waiting for news of missing relatives. Lin Tong-meng said he had been waiting at the site for word of his 11- and 12-year-old nephews. "I came back and forth all yesterday and now I'm here again," Lin said. The boy's mother and father were rescued soon after the quake. Their father also stood nearby, pacing close to the rubble in tears. Taiwan's government said in a statement 36 of the 38 dead were from the Wei-guan building, which was built in 1994. President-elect Tsai Ing-wen, who won election last month, said there needed to be a "general sorting out" of old buildings to make sure they were able to cope with disasters like earthquakes. "There needs to be a continued strengthening of their ability to deal with disasters," she said. Outgoing President Ma Ying-jeou, speaking to reporters at a Tainan hospital, said the government needed to be a better job in ensuring building quality. "In the near future, regarding building management, we will have some further improvements. We will definitely do this work well," Ma said. Reuters witnesses at the scene of the collapse saw large rectangular, commercial cans of cooking-oil packed inside wall cavities exposed by the damage, apparently having been used as building material. Chinese President Xi Jinping also conveyed condolences to the victims, state news agency Xinhua reported late on Sunday, and repeated Beijing's offer to provide help. China views self-ruled Taiwan as a wayward province, to be bought under its control by force if necessary. (Additional reporting by Faith Hung in TAIPEI and Megha Rajagopalan in BEIJING; Writing by Ben Blanchard; Editing by Paul Tait and Nick Macfie) ||||| Army soldiers guard the rescue staging area around a collapsed building complex in Tainan, Taiwan, Monday, Feb. 8, 2016. More than 100 people are believed to be still buried in the collapsed building... (Associated Press) TAINAN, Taiwan (AP) — At least four people, including an 8-year-old girl, were rescued Monday from a high-rise Taiwanese apartment building toppled by a powerful quake two days earlier, as frustration grew among families waiting for searchers to reach their buried loved ones. More than 100 people are believed to still be under the debris in a disaster that struck during the most important family holiday in the Chinese calendar — the Lunar New Year. Saturday's quake killed at least 38 people in Tainan city in southern Taiwan, all but two of them in the collapse of the 17-story building. Even though the 6.4-magnitude quake was shallow, few buildings were reported to have been damaged, which experts said was because Taiwan's building standards are high. Authorities have managed to rescue more than 170 people — the vast majority in the immediate hours after the quake — from the folded building using information about the building layout and the possible location of those trapped. Five survivors were believed to have been pulled out on Sunday, and at least four on Monday. One of them, Tsao Wei-ling, called out "Here I am" as rescuers dug through to find her, Taiwan's Eastern Broadcasting Corp. reported. She was found under the body of her husband, who had shielded her from a collapsed beam, the government-run Central News Agency reported. Tsao's husband and 2-year-son were found dead, and five other members of the family remained unaccounted for, it said. Teams also rescued on Monday a 42-year-old man from the building, and, later, an 8-year-old girl, who had been trapped for more than 61 hours. Mayor Lai Ching-Te told reporters he briefly exchanged words with the girl, Lin Su-chin. "She is awake, but looks dehydrated, lost some temperature but she's awake and her blood pressure is OK," he said. "I asked her if there's anything wrong with her body. She shook her head." Shortly afterward, rescue workers also pulled out a 28-year-old Vietnamese woman, identified as Chen Mei-jih, who had been trapped on what was the building's fifth floor. Family members of the missing flooded into the information center in search of their loved ones or to wait anxiously. Tensions rose as some relatives, losing patience, demanded to speak to rescue workers directly to get the latest information. A couple sitting in a small room where officials release information said they had heard no news about their son and his family, including their young grandsons. "Does that mean we are here to wait for bodies?" grandfather Liu Meng-hsun cried out angrily. Outside, a woman stood at the edge of the rubble shouting, "Your grandma is here!" Rescuers had detected life within the area where the 16th-floor apartment of her son and his family was thought to be, and were said to have heard the sound of a child. Her son, surnamed Wu, got out of the building soon after the quake, but his wife and their 4-year-old girl remained trapped, according to volunteers assisting the family. Earthquakes rattle Taiwan frequently. Most are minor and cause little or no damage, though a magnitude-7.6 quake in central Taiwan in 1999 killed more than 2,300 people. The spectacular fall of the high-rise, built in 1989, raised questions about whether its construction had been shoddy. The government says it will investigate whether the developer cut corners. Huang Jia-rui, a structural engineer in Tainan, said Taiwan's buildings aren't as quake-proof as Japan's, which is a leader in engineering quake-proof structures, but the island is catching up. The extended Lunar New Year holiday officially started Monday, but celebrations were subdued and both President Ma Ying-jeou and President-elect Tsai Ing-wen canceled the traditional handing out of envelopes of cash in their hometowns. ___ Associated Press writer Louise Watt and news assistant Henry Hou in Beijing, and Christopher Bodeen in Qingdao, China, contributed to this report. ||||| These crawls are part of an effort to archive pages as they are created and archive the pages that they refer to. That way, as the pages that are referenced are changed or taken from the web, a link to the version that was live when the page was written will be preserved.Then the Internet Archive hopes that references to these archived pages will be put in place of a link that would be otherwise be broken, or a companion link to allow people to see what was originally intended by a page's authors.The goal is to fix all broken links on the web . Crawls of supported "No More 404" sites.

– Two days after a powerful earthquake shook southern Taiwan, at least four more survivors have been pulled from the rubble of a collapsed 17-story apartment building in Tainan, the AP reports. A woman who called out "Here I am!" was found under the body of her husband, while rescuers also discovered a 42-year-old man and a 28-year-old Vietnamese woman. An 8-year-old girl was also pulled to safety. "She is awake, but looks dehydrated, lost some temperature," the Tainan mayor says. "I asked her if there's anything wrong with her body. She shook her head." The death toll is currently hovering at just under 40, but more than 100 people are still missing, per Reuters. So far, at least 170 survivors have been pulled from the wreckage of the building, which the Miami Herald says "folded like an accordion" during the 6.4-magnitude temblor. A rescuer tells the paper that "it takes a few hours to complete a search for just one household and sometimes it takes two hours just to go forward … 12 inches." Not many buildings were damaged in the quake, mainly because Taiwan holds high building standards. The government says it will investigate whether this building's construction was subpar, with both the outgoing and incoming Taiwanese presidents noting more work needs to be done to ensure building safety, per Reuters. Suspicions about this particular building were heightened by witnesses who say they spotted big commercial cans of cooking oil shoved into wall cavities as makeshift building materials. "I told my son not to buy an apartment here; it was suspiciously cheap," a man who's trying to help rescuers find his young grandsons tells the Herald.

Arthur was a very happy young man. He was a 26 year old engineering student. He loved life, he was an active member of a Christian church, devoting his life to the Lord. He participated in the praise group of the church in Revere and was very involved in all of the church activities. He loved hiking, biking, surfing and various other sports. There was never a bad time for him. He was always joyful and willing to help others, even going as far as feeding the homeless. He was happily engaged to a smart, kind-hearted medical student with a bright future. Our lives are are never going to be the same without him. His laughter filled our home and he will be greatly missed by us all.The Family of Arthur Medici needs all the support possible, both spiritually and financially. If you can please help in this cause. ||||| Marisa Medici said she begged her nephew to stay clear of Cape Cod’s shark-infested waters, but the ill-fated boogie boarder laughed off her fears. Arthur Medici, 26, became the state’s first shark attack fatality in 82 years on Saturday at Newcomb Hollow Beach in Wellfleet. ||||| Photo via Facebook Arthur Medici. REVERE — Paddling on his boogie board, getting in position to catch the next good wave at a Wellfleet beach early Saturday afternoon, Arthur Medici went underwater. Five or 10 yards away, Isaac Rocha heard a scream as his friend resurfaced. He saw a fin and blood in the water. He swam over, grabbed Medici, and began dragging him the almost 40 yards to shore. “It’s something that never passes your brain, your mind — you never think about that” happening, said Rocha, 16, of Everett, in a phone interview Sunday night. “It was just horrible, the worst feeling in the world,” he said. Advertisement Rocha tried to save him, tying a boogie board strap as a makeshift tourniquet around Medici’s leg. But the 26-year-old from Revere had been attacked by a shark and was declared dead at Cape Cod Hospital in Hyannis later Saturday. Get Fast Forward in your inbox: Forget yesterday's news. Get what you need today in this early-morning email. Sign Up Thank you for signing up! Sign up for more newsletters here Medici was planning to marry Rocha’s sister. The teen said he remembered Medici as a person full of love who was like an older brother to him. “He meant a lot for everyone,” Rocha said. “Everyone he came in touch with he was loved [by], and loved.” He said Medici “always fought for things he loved and who he loved.” Medici had had rings custom made in his native Brazil and planned to propose to Emily Rocha on a beach soon, according to Rocha. Advertisement Rocha said Medici was an engineering student, who had recently finished summer classes, and an avid body surfer, who frequently took him on trips to the Cape and Rhode Island. The two had surfed together at Newcomb Hollow until dusk the night before and also five days before that. “There isn’t a way to describe how much this hurts,” he said. On Sunday, the strong smell of the ocean at Revere Beach filled the air around the pale blue house on a quiet street where Medici lived with his aunt and uncle. Medici had moved in with them on Beachland Avenue about four years earlier, said Marisa Medici, his aunt, in a brief phone interview. Medici’s parents live in Brazil, she said. Itamar Medici, the victim’s father, wrote painfully of his loss on Facebook Sunday. Advertisement “Son... you left me. I’m broken and left without the will to live,” he posted in Portuguese. “I was fighting to give you everything and now . . . who’s going to keep what I was saving up to give to you. I don’t have the will to live anymore because nothing makes sense anymore . . . I love you for all of eternity,” he wrote. A GoFundMe page established to benefit Medici’s family had exceeded its $25,000 goal as of early Monday. Medici was active with his church, and loved hiking, biking, surfing, and other sports, according to a statement posted to the fund-raiser site. “Our lives are never going to be the same without him. His laughter filled our home and he will be greatly missed by us all,” the statement said. Medici was a student at Bunker Hill Community College, where he enrolled part time during the spring semester, according to a college statement. “The faculty, staff and administration of Bunker Hill Community College offer their sincerest condolences after the tragic death of Arthur Medici who was killed in a shark attack on Cape Cod Saturday afternoon,” according to the statement. Photo courtesy of Rosi Gava Arthur Medici. The college is offering support to faculty and students who may have been in class with Medici, according to college spokeswoman Brooke L. Yarborough. Richard Collins, director of Fitzgerald & Collins in Marlborough, visited the home on Beachland Avenue Sunday afternoon to discuss funeral services. He said as he was leaving that plans have not been finalized. Medici’s death was the first from a shark attack in more than 80 years, and only the fourth in Massachusetts history. It was not clear what kind of shark had bitten Medici. Saturday’s attack came after a New York man was injured by a shark while swimming near Truro last month. A previous shark attack near Truro in 2012 left another man injured while bodysurfing. Last month, Nathan Sears, Orleans’s harbormaster, wrote on Facebook that the “inshore waters off of Cape Cod are truly a wild place” and people should practice extreme caution while visiting the area. “Regardless of how much signage and information we provide, there still seems to be a concerning level of complacency,” Sears wrote. “People continue to risk entering and swimming in the water even after the recent incident in Truro where the man was bitten.” Sharks are drawn to the waters off the Cape by hundreds of seals, and residents in the area have seen shark sightings increase as the seal population has grown in the past few decades, officials have said. “There are two things we can’t control: Shark behavior and seal behavior... what does that leave us? We have to modify our behavior,” said Greg Skomal, program manager and senior scientist with the state Division of Marine Fisheries. Colin Sheehan sat with his 12-year-son, Dermott, on the edge of a sand dune on Newcomb Hollow Beach Sunday afternoon watching the ocean where Medici had been attacked. Sheehan, 51, said he had met Medici on the same beach a few days before the attack while they were changing out of their wetsuits. Medici was with a friend, he said, and looked like he was having a good time. When he saw Medici’s face in the paper Sunday, Sheehan said he started shaking and crying. “It’s surreal, everyone’s kind of in shock, “ Sheehan said. “[My son] and I would be in the water right now but it’s too scary. It went from hypothetical to reality.” He was not going in the water Sunday, he said, despite the picture-perfect day, but many other surfers did, disregarding a sign that said “No swimming, surfing etc. until further notice.” Underneath the sign was a memorial that had been set up with candles, shells, and flowers. Earlier in the day, beachgoers said surfers had a spotter standing on the dunes with binoculars looking out for sharks. Debee Tlumacki for The Boston Globe People paused near a make-shift memorial on Newcomb Hollow Beach in Wellfleet for shark attack victim Arthur Medici, who was killed by a shark Saturday while boogie boarding. Miranda Kielpinski, 28, of Harwich was taking advantage of the swell Sunday. What had happened was terrible, she said, but the ocean is a playground for these animals. “When you surf it’s a passion,” said Kielpinski. “We’re well of aware of what could happen.” Paul Fleming, 69, of Eastham said he was on Newcomb Hollow when the attack occurred. The retiree and lifelong surfer had watched as Medici was pulled out of the water Saturday. Sunday, he was back on the beach preparing to surf for a couple of hours. Surfing is something they live for, he said. “It’s still traumatic to me today right now and this is my solution for it,” Fleming said. “I need to, we all have to go out here. We cannot not go out here. We must do it. I’m nervous as hell, but I owe it to the young man who died yesterday.” As she sat on the shore Sunday, Pennsylvania resident Susan Ketchum, 55, said she couldn’t stop thinking about the young man who lost his life the day before. “I was paying homage to him silently in my chair,” she said. “Just thinking a lot about it. I didn’t know him but I love this place and I love the ocean.” Globe correspondent Debora Almeida contributed to this report. Lucas Phillips can be reached at [email protected] . John Hilliard can be reached at [email protected] . Cristela Guerra can be reached at [email protected] ||||| 'He meant the world to us,' friend of fatal shark attack victim says Isaac Rocha, who was with his friend, a 26-year-old Revere man who died after being attacked by a shark off Cape Cod, said he had the image of what happened stuck in his head. Rocha was spending the weekend on Cape Cod with the victim, identified as Arthur Medici. Rocha said the two arrived around 5:30 p.m. Friday and surfed at the same beach Friday evening before the sun went down. "He was actually teaching me how to catch some waves," Rocha said. They spent the night at a hotel before heading to Newcomb Hollow Beach around 10 a.m. Saturday, enjoying the mild late summer day. Family photo Arthur Medici "I was in the water with him yesterday," Rocha said. "We were surfing on boogie boards and I was about 5-10 yards from him. I saw him go down and then I saw him go back up and saw a lot of blood and he was screaming." Rocha said he swam to Medici as fast as I could. "I got to him and he wasn’t talking anymore," Rocha said. "I dragged him out of the water about 35 yards. I got him to the beach and, I was exhausted I couldn’t pull him back anymore. After that, I got the boogie board strap, his boogie board strap, and tried to tie it around his leg to stop the bleeding." He said several people came running in to help moments later. First responders performed CPR on Medici on the beach after the bite before he was transported to Cape Cod Hospital in Hyannis, where he was pronounced dead. Medici's death was the first fatal shark attack in Massachusetts since 1936. Medici was dating Rocha's sister. Rocha said Medici's death has been especially hard for her. "They were thinking about marriage and all that. It’s horrible," Rocha said. "We love him so much, he meant the word to us. He still means the world to us." A Go Fund Me setup to pay for the funeral of the 26-year-old engineering student said he loved life, participated in the praise group of the church in Revere and was very involved in all of the church activities. "He loved hiking, biking, surfing and various other sports," the page said. "Our lives are are never going to be the same without him. His laughter filled our home and he will be greatly missed by us all," it said. Click here to donate to the fund setup in his name AlertMe

– Marisa Medici was always concerned about her nephew, Arthur, when he went boogie boarding in what the Boston Herald describes as the "shark-infested waters" of Cape Cod. "Oh my gosh, that’s where he wanted to be every day. Every day. Always I asked him, 'Don’t go. Please, don’t go,'" Marisa Medici tells the Herald. But "he’d say, 'Aunt, they’re not going to bite me. The sharks don’t bite me. I’m Superman!'" But on Saturday, 26-year-old Arthur Medici became Cape Cod's first shark attack fatality in 82 years. Marisa Medici, whom Arthur lived with, says he left Friday night with Isaac Rocha, whom she describes as his future brother-in-law, for Newcomb Hollow Beach in Wellfleet, Mass. They set out for the water that night and again the next morning, Rocha tells WCVB. He describes what happened next to the Boston Globe as "just horrible, the worst feeling in the world." The shark attacked Arthur from behind, biting his legs and severing his femoral arteries, per his aunt. Rocha estimates he was 5 to 10 yards away when he saw Arthur going down, then saw a lot of blood and heard Arthur screaming. "And when (Arthur) came up out of the water, (Rocha) went to him to rescue him and take him to the sand," said Marisa Medici between tears; Rocha says Arthur was no longer speaking at that point. "Because the shark bit on the back of his legs, the calves, he lost a lot of blood. A lot of blood. Basically everything," Marisa Medici says. "When he was on the sand, he’d already lost the blood. They did CPR, they did everything. They didn’t save him." A GoFundMe campaign has been started to bring Arthur's body home to his native Brazil to be buried. He had been in the US four years, was studying engineering and was planning to marry his girlfriend of nearly two years.

self - eating , and comprises a multistep process of sequestration and subsequent degradation of intracellular material within specialised compartments ( refs 9 , 10 ) . autophagy is orchestrated by a subset of genes that were originally identified in yeast and are called autophagy - related genes ( atg ) , many of which have mammalian orthologues ( refs 10 , 11 ) . autophagy can be divided into different stages that ultimately result in lysosomal breakdown of cytoplasmatic material : initiation ; autophagosome formation ( nucleation , elongation and completion ) ; and maturation and degradation . atgs orchestrate the formation of autophagic vesicles from the phagophore / isolation membrane to the autophagosome and finally the autolysosome . the ulk atg13fip200 and the beclin-1hvps34p150 complexes mediate early nucleation events , whereas the two ubiquitin - like conjugation systems ( atg5atg12 and lc3-ii ) direct vesicle elongation and autophagosome formation . cellular material is finally sequestered within the autophagosome and thereby separated from the cytoplasm . intracellular material is degraded in autolysosomes , which result from a fusion of lysosomes with autophagosomes . importantly , autophagy is the complete process from initiation to degradation and not just the accumulation of autophagosomes . abbreviations : atg , autophagy - related protein ; beclin 1 , coiled - coil myosin - like bcl-2-interacting protein ; fip200 , 200 kda fak family kinase - interacting protein ; hvps34 , human vacuolar protein sorting - associated protein 34 ; lc3 , ( microtubule - associated protein ) light chain 3 ; mtor , mammalian / mechanistic target of rapamycin ; p150 , regulatory subunit of hvps34 ; p , phosphorylation ; ulk1/2 , unc-51-like kinase 1/2 . mechanisms of autophagy . following an initiating event , atgs orchestrate the formation of autophagic vesicles from the phagophore / isolation membrane to the autophagosome and finally the autolysosome . the ulk atg13fip200 and the beclin-1hvps34p150 complexes mediate early nucleation events , whereas the two ubiquitin - like conjugation systems ( atg5atg12 and lc3-ii ) direct vesicle elongation and autophagosome formation . cellular material is finally sequestered within the autophagosome and thereby separated from the cytoplasm . intracellular material is degraded in autolysosomes , which result from a fusion of lysosomes with autophagosomes . importantly , autophagy is the complete process from initiation to degradation and not just the accumulation of autophagosomes . abbreviations : atg , autophagy - related protein ; beclin 1 , coiled - coil myosin - like bcl-2-interacting protein ; fip200 , 200 kda fak family kinase - interacting protein ; hvps34 , human vacuolar protein sorting - associated protein 34 ; lc3 , ( microtubule - associated protein ) light chain 3 ; mtor , mammalian / mechanistic target of rapamycin ; p150 , regulatory subunit of hvps34 ; p , phosphorylation ; ulk1/2 , unc-51-like kinase 1/2 . initiation in mammalian cells starts with the activation of a serine / threonine kinase complex that contains ulk1/2 ( orthologues of the yeast protein atg1 ) , atg13 and fip200 ( rb1cc1 ) this complex transfers signals from the nutrient - sensing mtor kinase ( mtor ; mammalian / mechanistic target of rapamycin ) to initiate autophagy ( refs 12 , 13 , 14 , 15 ) . inhibition of mtor - induced phosphorylation of ulk and atg13 liberates the kinase activity of ulk , which subsequently phosphorylates itself , atg13 and fip200 . the ulk complex then accumulates at the initiating focus of vesicle formation : the isolation membrane or phagophore ( refs 13 , 14 , 15 ) . the further development of the isolation membrane / phagophore critically depends on the activity of the class iii phosphoinositide 3-kinase ( pi3k - iii ) hvps34 ( pik3c3 ; the orthologue of yeast vps34 ) and its formation of a complex with beclin 1 ( yeast atg6 ) and p150/hvps35 ( pik3r4 ; yeast vps15 ) ( refs 16 , 17 ) . vesicle elongation and completion from the isolation membrane / phagophore to a nascent autophagosome and the completed , closed autophagosome is mediated by two ubiquitin - like conjugation systems : the atg12 and atg8 conjugation systems ( ref . the ubiquitin - like atg12 is activated by atg7 and then temporarily binds to the e2-like enzyme atg10 before being transferred to atg5 . atg5 further reacts with atg16 to form a multimeric complex of atg12atg5atg16 ( refs 19 , 20 ) . in mammalian cells , several orthologues of yeast atg8 have been identified : map1lc3 ( lc3 ) , gabarapl2 ( gate16 ) , gabarap and gabarapl1 ( atg8l ) . the processing of the autophagosome marker lc3 has been investigated most thoroughly , and its stepwise conversion from a cytosolic to a membrane - bound form is exploited for the experimental measurement of autophagy ( ref . lc3 is synthesised as a precursor protein prolc3 and is immediately processed to lc3-i by atg4 through cleavage of the c - terminal amino acid . lc3 maturation completes with the reversible conjugation of lc3-i to phosphatidylethanolamine ( pe ) at the c - terminus by atg3 and atg7 to form lc3-ii on the surface of autophagosomes ( refs 19 , 20 ) . the atg12atg5atg16 complex is required for targeting of lc3 to the autophagosomal membrane and accelerated conjugation of lc3 to pe . atg8 , the yeast counterpart of lc3 , controls the expansion of the phagophore and the amount of atg8 directly correlates to the size of the autophagosomes ( refs 19 , 22 ) . therefore the assignment of the different atgs to corresponding stages and autophagic vesicles is to some degree academic . the maturation process encompasses the fusion of autophagosomes with lysosomes to form the end - stage vesicle of autophagy : the autolysosome . molecular mechanisms of autophagosome maturation are only recently emerging and involve the actions of lysosomal proteins lamp1 and lamp2 , the small gtpase rab7 ( rab7a ) , uvrag ( the protein product of the ultraviolet - radiation - resistance - associated gene ) and others ( ref . the tumour suppressor uvrag not only regulates the interaction of beclin 1 and hvps34 at the stage of vesicle nucleation but also plays an important role in the maturation step . uvrag directs so - called tethering proteins ( i.e. proteins that connect the autophagosome to its target ) to the autophagosomal membrane and thereby activates rab7 to facilitate fusion with lysosomes ( ref . the final autolysosome is an acidic vesicle wherein the intracellular material gets degraded by lysosomal hydrolases , especially cathepsins . amino acids and other constituent parts generated in this catabolic process are then released from the autolysosome to fuel cellular resources . in yeast , although mammalian lysosomal amino acid transporters have been described , a clear orthologue of atg22 in these higher species is yet to be defined . malignant transformation of a normal cell into a cancer cell results from accumulation of several mutations that override cellular safeguard mechanisms such as apoptosis or oncogene - induced senescence ( ref . currently it is unclear how autophagy is to be interpreted in the context of cancer . as outlined above , the unsolved paradox is that on the one hand its cytoprotective traits could clearly promote survival of both cancer and normal cells ( refs 1 , 3 ) , whereas on the other hand autophagy might suppress tumour growth through its connection to cell death , senescence and oxidative stress ( refs 6 , 7 , 25 , 26 , 27 , 28 ) . the genetic evidence that autophagy and cancer are linked is overwhelming ( refs 11 , 29 , 30 ) . we detail here in a piecemeal fashion the data that have accumulated from humans and mouse models about the function of atgs , their direct binding partners and their roles in either protecting against or promoting cancer . beclin 1 ( becn1 ) is a critical autophagy - regulating gene and provided the first human genetic link between autophagy and cancer . it is monoallelically deleted in ~50% of human breast , ovarian and prostate cancers and expressed only at low levels in brain tumours ( refs 31 , 32 , 33 ) . subsequent studies of genetically modified mice revealed that while bi - allelic loss of becn1 is embryonically lethal , mice that retain one copy of the gene are viable , but have a higher incidence of lymphomas , lung and liver carcinomas , as well as mammary hyperplasia and accelerated formation of premalignant lesions induced by hepatitis b virus , compared with wild - type animals ( refs 34 , 35 ) . in addition , reintroduction of becn1 into human mcf7 breast carcinoma cells , which express only trace amounts of beclin 1 , restores their autophagic capacity and inhibits their tumour - forming potential ( ref . beclin 1 is therefore a haploinsufficient tumour suppressor ( refs 34 , 35 ) . atg5 and atg7 are two other critical autophagy regulators that have been deleted in experimental animal models . unlike complete deletion of becn1 , deficiency in atg5 or atg7 is not embryonically lethal and mice are born normal without any apparent abnormalities ; however , both atg5and atg7 mice die within 24 h after birth , presumably as a result of an inability to compensate the neonatal starvation period that occurs after being cut off from the maternal circulation , when autophagy is normally transiently upregulated ( refs 3 , 36 ) . mice hemizygous for either atg5 or atg7 are born viable and develop normally . in contrast to becn1-hemizygous animals , however , they do not develop tumours ( refs 3 , 36 ) . intercrossing tumour - prone mice to recently developed conditional knockout mice for atg5 and atg7 ( refs 36 , 37 ) will seemingly be required for the spatial and temporal dissection of the contribution of these genes to cancer development . yeast atg4 has four mammalian orthologues , of which atg4c ( autophagin-3 ) is most widely expressed . atg4c - knockout animals are born viable , survive the neonatal starvation period and develop normally ( ref . spontaneous tumours arise at the same frequency as in wild - type controls ; however , they do have a higher susceptibility to develop fibrosarcomas after chemical carcinogenesis ( ref . a functional redundancy of the different atg4 proteins in mammals might explain the notion that atg4c deficiency does not alter basal autophagic activity in vivo and the fact that atg4c - deficient mice survive the neonatal starvation period ( ref . uvrag is a tumour suppressor gene that is monoallelically deleted in a significant proportion of human colorectal carcinomas , and uvrag expression in human hct116 colon carcinoma cells reduces the tumourigenic potential of these cells in xenograft studies ( ref . furthermore , uvrag is a target for frameshift mutations in colorectal and gastric carcinomas with microsatellite instability ( ref . a role for autophagy deficiency in intestinal tumourigenesis is further supported by the fact that frameshift mutations in other autophagy - related genes atg2b , atg5 , atg9b and atg12 have been found in up to 28% of human gastric and colorectal cancers with microsatellite instability ( ref . bif1 ( sh3glb1 ) is another protein that positively regulates autophagy , through interaction with uvrag and beclin 1 ( ref . b1f1-knockout mice are born viable and develop normally , without any apparent abnormalities except for an enlarged spleen . however they do have a higher propensity to develop spontaneous cancer ( mainly lymphomas and to a lesser extent solid tumours ) at an average age of 12 months . bif1 is thus a positive regulator of autophagy and a potential tumour suppressor ( ref . 41 ) . in summary , the available data from humans and mouse models where atgs or their direct positive modulators are lost or expressed at low levels point towards a tumour - suppressive role of autophagy . it is important to keep in mind , however , that in all the above mouse models autophagy inhibition involved deletion of the gene in the target cells embryonically . as a result , all the pathologies observed arose from cells that had always had impaired autophagy . these experiments thus do not clarify the role of acute autophagy loss at a later developmental stage , for instance in an established tumour , a scenario that likely occurs in vivo . in order to address this important question , further analysis is therefore required of conditional autophagy - deficient animals , by using inducible cre recombinases so that gene deletion can be achieved in the adult animal in a tissue- and tumour - specific manner . as indicated above , the control of autophagy is multifactorial and incompletely understood , but there is an emerging trend that tumour suppressors induce autophagy whereas oncogenes have the opposite effect ( refs 5 , 42 ) . many oncogenic and tumour - suppressive effects impact ultimately on mtor and complexes of beclin 1 and hvps34 ( beclin-1hvps34 ) , which are central to autophagy regulation in many contexts ( ref . these complexes therefore merit prior discussion in order to fully understand the control of autophagy by classic oncogenes and tumour suppressors ( fig . 2 ) . figure 2signalling networks of oncogenes and tumour suppressors that control autophagy . a multitude of pathways that are commonly deregulated in cancer control autophagy via its master switches mtor and the complex of beclin 1 and hvps34 ( beclin-1hvps34 ) . hypoxia and limited nutrient supply are frequently encountered in tumours and lead to activation of autophagy via engagement of the same networks . autophagy - inducing regulators are depicted in green , inhibiting regulators in red , and those that have a dual effect on autophagy in yellow . the asterisk indicates that the mechanism of ras - induced upregulation of autophagy in senescence remains to be fully elucidated . abbreviations : akt , rac - alpha serine / threonine - protein kinase ; ampk , amp - activated protein kinase ; arhi , aplasia ras homologue member i ( also known as diras3 for diras family , gtp - binding ras - like 3 ) ; bad , bcl-2-associated antagonist of cell death ; bcl-2 , b - cell cll / lymphoma 2 ( apoptosis regulator ) ; bcl - xl , b - cell lymphoma - extra large ; beclin 1 , coiled - coil myosin - like bcl-2-interacting protein ; bif1 , endophilin b1 ; bnip3(l ) , bcl2/adenovirus e1b 19 kda protein - interacting protein 3-(like ) ; dapk , death - associated protein kinase ; dram1 , damage - regulated autophagy modulator protein 1 ; erk , extracellular - signal - regulated kinase ; hif1 , hypoxia - inducible factor 1 ; map1b , microtubule - associated protein 1b ; mcl-1 , induced myeloid leukaemia cell differentiation protein ; mtorc1 , mtor complex 1 ; p53 , cellular tumour antigen p53 ; p73 , tumour protein p73 ; pdgfr , platelet - derived growth factors receptor ; pdk1 , 3-phosphoinositide - dependent protein kinase 1 ; pi3k - i , phosphoinositide 3-kinase class i ; pten , phosphatase and tensin homologue ; ras , gtpase ras ; rtk , receptor tyrosine kinase ; rheb , ras homologue enriched in brain ; stk11 , serine / threonine - protein kinase 11 ( also known as lkb1 ) ; tsc1 , hamartin , tuberous sclerosis 1 protein ; tsc2 , tuberin , tuberous sclerosis 2 protein ; uvrag , uv - radiation - resistance - associated gene . signalling networks of oncogenes and tumour suppressors that control autophagy . a multitude of pathways that are commonly deregulated in cancer control autophagy via its master switches mtor and the complex of beclin 1 and hvps34 ( beclin-1hvps34 ) . hypoxia and limited nutrient supply are frequently encountered in tumours and lead to activation of autophagy via engagement of the same networks . autophagy - inducing regulators are depicted in green , inhibiting regulators in red , and those that have a dual effect on autophagy in yellow . the asterisk indicates that the mechanism of ras - induced upregulation of autophagy in senescence remains to be fully elucidated . abbreviations : akt , rac - alpha serine / threonine - protein kinase ; ampk , amp - activated protein kinase ; arhi , aplasia ras homologue member i ( also known as diras3 for diras family , gtp - binding ras - like 3 ) ; bad , bcl-2-associated antagonist of cell death ; bcl-2 , b - cell cll / lymphoma 2 ( apoptosis regulator ) ; bcl - xl , b - cell lymphoma - extra large ; beclin 1 , coiled - coil myosin - like bcl-2-interacting protein ; bif1 , endophilin b1 ; bnip3(l ) , bcl2/adenovirus e1b 19 kda protein - interacting protein 3-(like ) ; dapk , death - associated protein kinase ; dram1 , damage - regulated autophagy modulator protein 1 ; erk , extracellular - signal - regulated kinase ; hif1 , hypoxia - inducible factor 1 ; map1b , microtubule - associated protein 1b ; mcl-1 , induced myeloid leukaemia cell differentiation protein ; mtorc1 , mtor complex 1 ; p53 , cellular tumour antigen p53 ; p73 , tumour protein p73 ; pdgfr , platelet - derived growth factors receptor ; pdk1 , 3-phosphoinositide - dependent protein kinase 1 ; pi3k - i , phosphoinositide 3-kinase class i ; pten , phosphatase and tensin homologue ; ras , gtpase ras ; rtk , receptor tyrosine kinase ; rheb , ras homologue enriched in brain ; stk11 , serine / threonine - protein kinase 11 ( also known as lkb1 ) ; tsc1 , hamartin , tuberous sclerosis 1 protein ; tsc2 , tuberin , tuberous sclerosis 2 protein ; uvrag , uv - radiation - resistance - associated gene . the serine / threonine kinase mtor is a focal point for the action of many oncogenic and metabolic events as well as the control of autophagy . many regulators of mtor signalling , especially the pi3k akt pten pathway , are frequently deregulated in human tumours ( ref . these have different components , most notably raptor ( raptor ; regulatory - associated protein of mtor , complex 1 ) for mtorc1 and rictor ( rictor ; rapamycin - insensitive companion of mtor , complex 2 ) for mtorc2 ( refs 46 , 47 ) . activation of mtorc1 leads to protein synthesis via the actions of s6k1 ( rps6kb1 , ribosomal protein s6 kinase , 70 kda , polypeptide 1 ) and 4ebp1 ( eif4ebp1 , eukaryotic translation initiation factor 4e binding protein 1 ) . it activates akt via phosphorylation and enhances the expression of hif-1 ( hif1a ; hypoxia - inducible factor 1 ) ( refs 48 , 49 ) . while driving translation , mtor also inhibits autophagy and this effect is mediated via mtorc1 and its interaction with the ulk the net effect of mtor activation is cell growth , proliferation and cell survival ( refs 45 , 50 ) . mtor activity is pivotal in determining whether the net effect from signals within the cell is pro- or anti - autophagic . beclin 1 was initially identified as a bcl-2 ( bcl2)-binding protein and was found to have tumour suppressor functions ( ref . it has emerged , however , that beclin 1 function is multifaceted and not restricted to the regulation of autophagy . it is part of a multiprotein complex that regulates autophagy through variation of its composition ( fig . beclin 1 forms a heterodimer that is stabilised via binding to antiapoptotic members of the bcl-2 family [ bcl-2 , bcl - xl ( bcl2l1 ) , mcl-1 ( mcl1 ) ] through its bcl-2-homology domain 3 ( bh3 ) domain ( refs 51 , 52 ) . monomerisation of beclin 1 is required for it to associate with and activate the pi3k - iii hvps34 , which is critical for the formation of autophagosomes . therefore , tumour - associated perturbations of antiapoptotic bcl-2 family members can cause profound inhibition of autophagy by preventing the formation of a beclin-1hvps34 complex ( ref . it has diverse protein - binding domains that allow the formation of different complexes with opposing functions on autophagy . certain stimuli , for example starvation , disrupt the binding of bcl-2 proteins from the bh3 domain of beclin 1 . currently four regulators of the beclin-1hvps34 complex have been identified that determine its pro- or anti - autophagic activity . autophagy - inducing regulators / complexes are depicted in green , inhibiting regulators / complexes in red , and those that have an undetermined role in yellow . abbreviations : ambra1 , activating molecule in beclin-1-regulated autophagy protein 1 ; atg , autophagy - related protein ; barkor , beclin-1-associated autophagy - related key regulator ; bcl-2 , b - cell cll / lymphoma 2 ; bcl - xl , b - cell lymphoma - extra large ; beclin 1 , coiled - coil myosin - like bcl-2-interacting protein ; bh3 , bcl-2 homology domain 3 ; ecd , evolutionarily conserved domain ; mcl-1 , induced myeloid leukaemia cell differentiation protein ; rubicon , run domain and cysteine - rich domain containing , beclin-1-interacting protein ; uvrag , ultraviolet - radiation - resistance - associated gene . regulation of autophagy by beclin 1 complexes . it has diverse protein - binding domains that allow the formation of different complexes with opposing functions on autophagy . certain stimuli , for example starvation , disrupt the binding of bcl-2 proteins from the bh3 domain of beclin 1 . currently four regulators of the beclin-1hvps34 complex have been identified that determine its pro- or anti - autophagic activity . autophagy - inducing regulators / complexes are depicted in green , inhibiting regulators / complexes in red , and those that have an undetermined role in yellow . abbreviations : ambra1 , activating molecule in beclin-1-regulated autophagy protein 1 ; atg , autophagy - related protein ; barkor , beclin-1-associated autophagy - related key regulator ; bcl-2 , b - cell cll / lymphoma 2 ; bcl - xl , b - cell lymphoma - extra large ; beclin 1 , coiled - coil myosin - like bcl-2-interacting protein ; bh3 , bcl-2 homology domain 3 ; ecd , evolutionarily conserved domain ; mcl-1 , induced myeloid leukaemia cell differentiation protein ; rubicon , run domain and cysteine - rich domain containing , beclin-1-interacting protein ; uvrag , ultraviolet - radiation - resistance - associated gene . the beclin-1hvps34p150 core complex is complemented by different regulatory proteins that bind to beclin 1 through domains other than bh3 and define its role in autophagy . to date , three different forms of the complex have been identified , all of which have different functions . they contain either atg14/barkor ( beclin-1-associated autophagy - related key regulator ) or uvrag alone , or both uvrag and rubicon ( run domain and cysteine - rich domain containing ) . it has been proposed that the atg14/barkor - containing complex targets hvps34 activity towards the isolation membrane and thus functions in autophagosome formation , and that the uvrag - containing complex promotes autophagosome and endosome maturation ( ref . atg14/barkor positively regulates autophagy , promotes translocation of beclin 1 to autophagosomes and competes with uvrag for the same binding site on beclin 1 ( ref . by contrast , the uvrag- and rubicon - containing complex suppresses autophagosome and endosome maturation ( refs 56 , 57 ) . knockdown of atg14/barkor inhibits autophagy whereas knockdown of rubicon has the opposite effect , providing further evidence that beclin 1 has multiple roles in autophagy through the formation of complexes with opposing actions ( fig . 3 ) . although perturbation of beclin 1 clearly has implications for cancer , a role for atg14/barkor in cancer has not yet been defined . ambra1 is another protein that binds the beclin-1hvps34 complex , with a role in the regulation of autophagy in neuronal development ( ref . however , as with atg14/barkor , its role in autophagy regulation has also not yet been extended to cancer . as outlined above , many oncogenes and tumour suppressors exert opposing effects on autophagy , often through direct or indirect regulation of mtor and beclin-1hvps34 , but also through currently unknown mechanisms . in the following examples we outline the reported effects of tumour - associated proteins on both autophagy and apoptosis . pi3k - i ( class i phosphoinositide 3-kinase ) is a lipid kinase activated via receptor tyrosine kinases ( rtks ) by multiple mechanisms ( refs 44 , 59 ) . this leads to cell growth and cell proliferation and the concomitant inhibition of autophagy by activation of mtor . since rtks and their downstream effectors are frequently mutated in cancer , activation in the pi3k - i pathway is very common in sporadic tumours ( ref . activated pi3k - i generates the second messenger phosphatidylinositol 3,4,5-trisphosphate [ ptdins(3,4,5)p3 ] , which then leads to activation / phosphorylation of akt via 3-phosphoinositide - dependent protein kinase 1 ( pdpk1/pdk1 ) . akt phosphorylates and inhibits tuberous sclerosis protein 2 ( tsc2 ) , which as a result permits rheb ( rheb ) to activate mtorc1 ( ref . akt can also activate mtor independently of tsc2 , via pras40 ( akt1s1 ; proline - rich akt - substrate 40 kda ) . in summary , the net effect of pi3k - i activation is activation of mtor with subsequent inhibition of autophagy ( refs 45 , 50 ) . pten ( phosphatase with tensin homologue ) is mutated in multiple cancer types and is the major target for mutation in cowden disease , a cancer predisposition syndrome ( ref . pten negatively regulates pi3k - i and thereby alleviates the inhibitory effects of mtor on autophagy . loss of pten is the most common mechanism of pi3k - i activation and is the second most frequently mutated tumour suppressor in human cancer ( ref . erk pathway is deregulated in many cancers and has a central role in mtor activation independent of akt . oncogenic hras - v12 has been reported to suppress protein degradation via activation of pi3k - i in nih3t3 cells ( ref . 62 ) , whereas in nontransformed imr90 human diploid fibroblasts , hras - v12 induces senescence with concomitant increased autophagy ( ref . the role of erk ( mapk1 , mitogen - activated protein kinase 1 ) in autophagy is also multifactorial . erk has been shown in different in vitro settings to induce autophagy ( refs 63 , 64 , 65 ) . recent findings indicate that this may occur through upregulation of beclin 1 and destabilisation of mtor via induction of tsc . interestingly in this context , basal activity of mek ( map2k1)/erk conferred basal levels of mtor and beclin 1 that were incapable of triggering autophagy ( ref . by contrast to these reports , however , it has also been shown that erk can inhibit tsc2 and promotes tumourigenesis in vitro and in vivo ( ref . stk11 ( serine / threonine kinase 11 ; also known as lkb1 ) is a tumour suppressor that is mutated in patients with hereditary intestinal polyposis ( peutz jeghers syndrome ) , which leads to a cumulative lifetime risk of cancer at age 70 of ~90% ( ref . in addition , mutations in stk11 are found in a high percentage of sporadically occurring lung malignancies . stk11 is a positive regulator of autophagy through the actions of ampk ( amp - activated protein kinase ) and mtor . jeghers syndrome ( heterozygous for stk11 ) with the mtor inhibitor rapamycin significantly reduced the tumour burden ( refs 68 , 69 ) . dapk1 ( death - associated protein kinase 1 ) has tumour - suppressive functions and is epigenetically silenced in a variety of human tumours ( ref . dapk was believed to be a positive regulator of autophagy through interaction with lc3-interacting microtubule - associated protein map1b and disruption of the beclin-1bcl - xl complex ( ref . recent data , however , showed that dapk is a positive regulator of mtorc1 through interaction with tsc2 ( ref . how this finding relates to the net effect of dapk on autophagy has not been examined . the tumour suppressor arhi ( aplasia ras homologue member i ; also known as diras3 for diras family , gtp - binding ras - like 3 ) is downregulated in more than 60% of ovarian cancer ( ref . it induces autophagy by upregulation of atg4 and blocking pi3k - i and therefore mtor ( ref . in addition , its expression leads to tumour dormancy in ovarian cancer xenograft models , which can be reversed upon treatment with chloroquine , a pharmacological inhibitor of lysosomal function and , as a result , autophagy ( ref . p53 ( tp53 ) is a major tumour suppressor , being mutated or lost in ~50% of all human cancers ( ref . 75 ) . in response to various forms of cellular stress , p53 becomes activated , leading to multiple phenotypic effects including induction of cell - cycle arrest and cell death ( ref . since p53 has been shown to respond to , and also to modulate , metabolic stress , it is perhaps no surprise that p53 has also been found to regulate autophagy ( refs 77 , 78 , 79 ) . the way in which p53 regulates autophagy , however , appears to be dependent on context . when elevated by cellular stress , p53 accumulates in the nucleus and activates target genes that mediate its tumour - suppressive effects . one of these genes , dram1 ( damage - regulated - autophagy modulator ) , encodes a phylogenetically conserved lysosomal protein that promotes autophagy ( refs 77 , 80 , 81 ) . interestingly , dram1 was also found to be required for p53-induced programmed cell death , although the mechanism underlying the interplay between dram1 , autophagy and apoptosis is yet to be determined ( ref . p73 ( tp73 ) , a closely related protein to p53 , has also been shown to modulate dram1 and autophagy , although autophagy induced by p73 was found to be independent of dram1 ( ref . 82 ) . since this points to other target genes of p53/p73 being involved in autophagy regulation , it is interesting to note that sestrin 2 ( sesn2 ) has also been linked to both p53 and p73 ( refs 83 , 84 ) . in an independent study , sestrins have been shown to modulate mtor through ampk ( ref . a link has now also been reported between p53 , sestrin 2 and autophagy ( ref . 86 ) , although the role of sestrin 2 in p73-driven autophagy is yet to be explored . in the absence of cellular stress , this effect , however , does not involve gene activation and occurs through a cytoplasmic mechanism at the endoplasmic reticulum ( ref . pharmacological inhibition or genetic ablation of p53 , both in vitro and in vivo , was shown to induce autophagy . although the induction and inhibition of autophagy by p53 are mechanistically distinct and therefore seemingly separable , it would be interesting to study the balance of these two effects when both are active are they opposing or mutually exclusive ? in this regard , it is interesting to note that certain tumour - derived mutants of p53 can inhibit autophagy through the cytoplasmic mechanism , but they do not cause the activation of dram1 or sestrin 2 that would be required for the induction of autophagy ( ref . therefore , it would be conceivable that autophagy would be reduced through both lack of induction as well as enforced inhibition . arf [ alternative reading frame of the cdkn2a ( ink4a ) locus ] is a bona fide tumour suppressor that is known to induce p53 levels following oncogenic stress and as a result has been shown to induce p53-dependent autophagy and thereby to enhance cell death . arf - induced autophagy might therefore contribute to its tumour - suppressive function ( ref . arf can also induce autophagy in the absence of p53 , probably through interaction with bcl - xl which normally inhibits the beclin-1hvps34 complex ( ref . . a smaller truncated form of arf , smarf ( resulting from initiation from an alternative internal methionine ) , has also recently been found to modulate autophagy in a p53-independent manner . in this context , smarf is considered to induce autophagy at mitochondria and causes induction of a cell death dependent on autophagy genes ( ref . in addition to the tumour suppressors and oncogenes discussed above , which have been shown to have an active role in autophagy regulation , several other tumour - associated factors could be postulated to modulate autophagy given their connection to pathways that have been previously implicated in autophagy regulation . as an element of speculation is involved , an exhaustive list of such factors could be generated ; we feel , however , that the factors listed below are worthy of discussion even if further studies are required to clarify a connection to autophagy regulation and the extent to which this may be important for the role of the factor in tumour development . nf1 ( neurofibromin ) is a tumour suppressor that antagonises ras , and loss - of - function mutations of nf1 are associated with the familial neurofibromatosis type 1 tumour syndrome ( recklinghausen disease ) , which is characterised by development of benign tumours of the nervous system , as well as a more general predisposition to cancer ( ref . complicating understanding of the role of nf1 is the fact that acute loss of nf1 in human diploid fibroblasts leads to a transient upregulation of ras , but ultimately suppresses the ras pi3k - i pathway and leads to senescence . autophagy has not been examined in this context but might well be upregulated given its crucial role in senescence ( ref . redd1 ( regulated in development and dna - damage responses 1 ; ddit4 ) is induced upon hypoxia and inhibits mtorc1 through activation of tsc1/tsc2 . redd1 expression is decreased in ~30% of breast and prostate carcinomas and therefore mtor inhibition by redd1 might prevent tumourigenesis . indeed , xenografts with loss of redd1 promoted tumour growth in nude mice ( refs 92 , 93 ) . given the impact of redd1 on mtor ( ref . 94 ) , it would be predicted that changes in redd1 would affect autophagy , but this has not yet been directly addressed . deptor ( depdc6 ) is a newly identified mtor - interacting protein with an unknown role in autophagy . it is expressed at low levels in most cancers but high levels in multiple myeloma cells ( ref . loss of deptor leads to activation of mtor targets and akt , whereas overexpression inhibits mtorc1 but activates pi3k - i akt signalling ( ref . the mtor and beclin-1hvps34 complexes are targeted by a multitude of different oncogenes and tumour suppressors , which thereby regulate autophagy . new players are constantly being identified and new links are being made , making the regulation of autophagy in cancer incredibly complex . it is currently unclear how loss of autophagy contributes to de novo tumour formation and how to interpret autophagy in the context of already established tumours . there is , however , accumulating evidence as outlined above that autophagy is a tumour - suppressive mechanism . several reports have now provided potential explanations as to how autophagy may function in tumour suppression , including roles in cell death , senescence and the management of metabolic stress . the role and mechanisms of autophagy in promoting cell survival in contexts such as nutrient deprivation are unequivocal . it is also without question that autophagy accompanies cell death in certain scenarios , although the exact contribution of autophagy is complex and less well defined . in systems where apoptosis was inhibited , either genetically or pharmacologically , cell death dependent on atgs was reported ( refs 96 , 97 ) ; in other words , inhibition of certain atgs ( atg5 , beclin 1 , atg7 ) suppressed cell death . in one report , where cells were treated with the caspase inhibitor zvad - fmk to inhibit caspase - dependent death , it was proposed that the cell death was mechanistically driven via the selective autophagic degradation of catalase , which subsequently overloads the cell with damaging ros ( ref . . a more direct role of atgs in cell death has also been shown : cleavage of atg5 has been reported to occur following cell death induction and this cleaved form has a direct proapoptotic role ( ref . this could indicate , therefore , that in studies where cell death has been compromised by atg5 knockdown , incorrect conclusions may have been drawn that the cell death observed was dependent on autophagy . clearance of dying cells during salivary gland development in drosophila melanogaster involves autophagy and in this context it appears that the full - blown cell death response is dependent on caspases and atgs ( ref . evidence also suggests a non - cell - autonomous role of autophagy in cell death , which extends the housekeeping functions of autophagy to a multicellular level . in an in vitro mouse model of embryonic development , inhibition of autophagy prevented the upregulation of two important cell - surface engulfment signals phosphatidylserine and lysophosphatidylcholine in cells destined to die ( ref . inhibition of autophagy in this system seems to result in cell death , but it is really the energy - dependent expression of engulfment signals that is impeded , which causes the accumulation of cellular corpses by default , that is at play . exogenous methylpyruvate is an alternative source of energy and its addition compensates for the low levels of atp in autophagy - deficient cells , leading to expression of the aforementioned engulfment signals . in an vivo context , it is notable that embryonic atg5-null mice display reduced phagocytosis of dead cells in lung and retinal tissue , pointing to the wider implications of this phenomenon and to the caution that should be employed when dying cells seemingly arise following autophagy inhibition ( ref . atgs facilitate cell death , but it is arguable that a situation has not yet been observed where a cell actually dies solely from autophagy . furthermore , as discussed above , the role of autophagy in cell death is not restricted to cell - autonomous effects . therefore , the term autophagic cell death ( or programmed cell death type ii ) has to be used with caution . it has been suggested it be replaced with the term cell death with autophagy as it is now widely considered that autophagy can be a component in cell death , perhaps as a permissive signal , but not its sole perpetrator ( ref . sustained growth arrest , like programmed cell death , is an important mechanism to counteract tumour growth in vivo and has recently been shown to be critically linked with autophagy ( ref . senescence is a critical barrier against malignant transformation and an important effector programme of chemotherapy . it is defined as an irreversible cell cycle arrest of viable and metabolically active cells following various endogenous and exogenous stresses ( ref . - v12-infected human diploid fibroblasts , autophagy is activated and its inhibition resulted in delayed onset of the senescent phenotype ( ref . tumour dormancy generally describes a phase of apparent stasis in tumour growth and is mechanistically subdivided into two models . single - cell dormancy is a phase of prolonged cell cycle arrest that can be overcome upon cell - autonomous genetic changes or alterations in the microenvironment . according to the micrometastasis model , tumour dormancy is a balanced state of cell renewal and cell death ( ref . 104 ) . ( both dormancy and senescence are not to be confused with quiescence , which is a physiological normal resting state of a cell . ) arhi expression induces autophagy and leads to tumour dormancy in ovarian cancer xenograft models , which can be reversed upon treatment with chloroquine , a pharmacological inhibitor of lysosomal function and therefore autophagy ( ref . when taken together , these reports clearly emphasise that growth arrest and autophagy are intertwined , and tentatively posit that autophagy and its role in senescence and dormancy may be a facet of tumour suppression in multiple cancers . metabolic stress , as a result of either insufficient nutrient / oxygen supply or increased energetic demands of rapidly dividing tumour cells , induces autophagy as an alternative source of energy and metabolites . enhanced autophagy is frequently found in hypoxic regions of tumours and contributes to cell survival ( ref . initially , it is therefore illogical how loss of autophagy contributes to tumour formation ( refs 32 , 34 , 35 ) . the first contribution to solve this conundrum came from the observation that metabolic stress promotes necrotic cell death in vivo and in vitro within cells that are defective in both autophagy and apoptosis . necrotic cell death was associated with a strong inflammatory response , which ultimately enhanced tumour growth ( ref . this therefore provides one explanation of how autophagy may be tumour suppressive through its capacity to impede necrosis . whether this is a factor , however , downstream of chemotherapeutic drugs that induce cell death through necrosis is an interesting question and worthy of further investigation ( refs 106 , 107 ) . meanwhile it is becoming increasingly substantiated that autophagy reduces oxidative stress , maintains protein and organelle quality control and thereby limits cellular damage ( refs 27 , 28 ) . metabolic stress leads to accumulation of ros , damaged proteins and damaged organelles such as mitochondria ( which are in turn additional sources of ros ) and impedes genetic stability when compensatory mechanisms fail . autophagy is a critical countermeasure following metabolic insults and attenuates these changes , thereby promoting cellular survival . in different studies , autophagy - defective tumour cells were indeed more susceptible to cell death but , importantly , at the same time were also more susceptible to genomic damage and possessed greatly enhanced tumourigenic potential when compared with autophagy - competent cells in vivo ( refs 27 , 28 ) . sequestosome 1 ( sqstm1 ; p62 ) has been identified as the critical molecular link between defective autophagy , genomic instability and tumourigenesis ( ref . p62 is an adapter protein that links polyubiquitinated proteins or aggregates to atg8/lc3 on the surface of autophagosomes . importantly , it is also a decisive element in modulating different molecular pathways , such as the nuclear factor nf-b pathway through recruitment of different signalling molecules and the extrinsic cell death pathway by promoting aggregation of caspase 8 ( ref . p62 is frequently upregulated in human tumours and of utmost importance in controlling oxidative stress and tumour growth ( refs 26 , 109 ) . tumour cells , therefore , with impairment in both apoptosis and autophagy preferably accumulate p62 under stress , which thereby promotes tumourigenesis ( ref . , metabolic stress leads to increased production of ros that in turn were responsible for accumulation of p62 . p62 itself was also causative for further oxidative damage , accumulation of damaged mitochondria , an enhanced induction of the protein - folding machinery in the endoplasmatic reticulum , and a dna - damage response . elevated levels of p62 suppressed the activation of target genes of nf-b . in ras - induced lung tumours , p62 is essential for tumour formation , but in contrast to the observation by mathew et al . these differences in nf-b activation are not readily explained and may be due to the versatility of p62 in activating different pathways ( ref . nonetheless , p62 accumulation is clearly causative for tumourigenesis and exemplifies how cancer progression can be affected by the selective autophagic degradation of a specific protein . figure 4 illustrates how the metabolic capacity of autophagy might be the decisive factor for proliferation control in tumourigenesis . figure 4autophagy manages cellular stress to counteract tumour growth . in autophagy - competent cells , cellular stress leads either to cell death , growth arrest in the form of premature senescence , or survival . if the autophagic capacity falls below a threshold that is necessary to maintain cell integrity , for example through genetic alterations or pharmaceutical intervention , cells are unable to compensate metabolic stress . as a result , necrotic cell death occurs and causes attraction of tumour - promoting macrophages . in surviving cells , however , failure to clear p62 ( sequestosome 1 ) and p62-associated aggregates results in further accumulation of ros ( reactive oxygen species ) , damaged proteins and organelles , altered cell signalling and dna damage . clinically , this phase might present as an initial tumour remission . however , the acquisition of growth - promoting mutations in a subset of cells might potentially lead to more aggressive tumour cells . cellular stress leads either to cell death , growth arrest in the form of premature senescence , or survival . if the autophagic capacity falls below a threshold that is necessary to maintain cell integrity , for example through genetic alterations or pharmaceutical intervention , cells are unable to compensate metabolic stress . as a result , necrotic cell death occurs and causes attraction of tumour - promoting macrophages . in surviving cells , however , failure to clear p62 ( sequestosome 1 ) and p62-associated aggregates results in further accumulation of ros ( reactive oxygen species ) , damaged proteins and organelles , altered cell signalling and dna damage . clinically , this phase might present as an initial tumour remission . however , the acquisition of growth - promoting mutations in a subset of cells might potentially lead to more aggressive tumour cells . with regard to the complexity and dichotomy of autophagy in cell death and tumour biology and limited treatment data from in vivo studies , can autophagy be modulated for the benefit of cancer therapy ? as a result of the survival effects of autophagy that were initially observed in vitro , the suggestion would have been that autophagy inhibition , in combination with standard chemotherapy , would be beneficial for tumour therapy . when we consider , however , the effects this may have on a necrosis - driven protumour inflammatory response or the effects on impeding cellular senescence , one would perhaps aver that autophagy promotion would be the way to go . nonetheless , several recent reports have shown that pharmacological inhibition of autophagy with chloroquine might be beneficial for tumour therapy ( refs 74 , 111 ) . the effects of chloroquine are , however , not limited to autophagy inhibition , causing , among other things , inhibition of lysosomal function in general , and it is important to note that in vivo genetic verification that the effects of chloroquine in these settings was through modulation of autophagy is yet to be established . in this regard , it is notable that a separate study analysing the therapeutic effectiveness of chloroquine revealed prodeath effects of autophagy . in this context , inhibition of caspases in an autophagy - deficient background , but not in autophagy - competent cells , reduced the cell death seen following chloroquine treatment . this would indicate , therefore , that cell death downstream of chloroquine in this setting is , in part , autophagy dependent ( ref . another study has also recently examined the regulation of autophagy by a doxycycline ( dox)-regulatable arhi - encoding gene ( diras3 ) in xenografts . treatment of mice carrying these xenografts with dox causes induction of arhi and autophagy and this led to reduced tumour growth compared with untreated animals . upon removal of dox , arhi and autophagy were reduced and rapid tumour outgrowth was observed . however , when arhi expression was induced in mice treated with chloroquine at the same time to inhibit autophagy , xenograft growth was rapidly diminished after withdrawal of dox ( and chloroquine ) ( ref . , a possible interpretation of these finding is that genetic and pharmacological ablation of autophagy produce different results and again point towards alternative or additional therapeutic effects of chloroquine in different contexts . more studies are therefore required to understand the relevance of autophagy following treatment with chloroquine in different settings . when considering targeting autophagy therapeutically , the effects on normal as well as tumour cells must always be considered . this is no more relevant than with autophagy , which has major homeostatic roles within our normal tissues . for example , the selective ablation of autophagy in the brains of mice has been shown to lead to neurodegenerative disease without any other accompanying mutation , indicating that the systemic modulation of autophagy may be naive ( refs 37 , 113 ) . as a result , it seems clear that we perhaps need to understand more about the selective control of autophagy in different settings to enable the bespoke targeting of autophagy to hit diseased cells , but not normal tissue . an understanding of the signalling pathways that talk to the autophagy machinery in response to different forms of cellular stress to bring about different effects may therefore be the key . in this regard , a recent report has identified that signalling from pdgf ( platelet - derived growth factor ) receptors is a permissive signal for hypoxia - driven autophagy while seemingly having no effects on autophagy driven by other stimuli . since autocrine pdgfr signalling and hypoxia are both tumour - associated events this may well be a paradigm for the identification of autophagic signalling pathways that could be utilised for targeting tumour - selective autophagy , and further studies of this , and other pathways , undoubtedly merit further investigation ( refs 114 , 115 , autophagy is important for development and cellular homeostasis , and lies at the intersection of life and death . more and more evidence is accumulating , however , that autophagy is a tumour - suppressive mechanism , with bonds to the control of oxidative damage , cell death and oncogene - induced senescence . looking at autophagy from a metabolism angle provides explanation of how loss of a cytoprotective mechanism facilitates tumour development through mitigating genomic stress . in line with these desired tumour - suppressive functions , autophagy - enhancing therapy may be as promising a therapeutic strategy as the simple notion of inhibiting autophagy to enhance cell death . it is undoubted , however , that our current understanding of autophagy is incomplete . as more genetic models of autophagy inhibition are developed , which allow the spatial and temporal control of autophagy , this should enable the more effective targeting of autophagy in a both a selective and bespoke manner .

autophagy is a catabolic membrane - trafficking process that leads to sequestration and degradation of intracellular material within lysosomes . it is executed at basal levels in every cell and promotes cellular homeostasis by regulating organelle and protein turnover . in response to various forms of cellular stress , however , the levels and cargoes of autophagy can be modulated . in nutrient - deprived states , for example , autophagy can be activated to degrade cargoes for cell - autonomous energy production to promote cell survival . in other contexts , in contrast , autophagy has been shown to contribute to cell death . given these dual effects in regulating cell viability , it is no surprise that autophagy has implications in both the genesis and treatment of malignant disease . in this review , we provide a comprehensive appraisal of the way in which oncogenes and tumour suppressor genes regulate autophagy . in addition , we address the current evidence from human cancer and animal models that has aided our understanding of the role of autophagy in tumour progression . finally , the potential for targeting autophagy therapeutically is discussed in light of the functions of autophagy at different stages of tumour progression and in normal tissues .

a.m.n . , and a.r.p . from the natural sciences and engineering research council ( nserc ) of canada . was also supported by the canada foundation for innovation ( project 28276 ) and the new brunswick innovation foundation ( project rif2012006 ) . f.f.m . was supported by the postdoctoral fellowship program from the consejo nacional de ciencia y tecnologa ( conacyt ) , mexico .

abstractthe thing about plastid genomes in nonphotosynthetic plants and algae is that they are usually very small and highly compact . this is not surprising : a heterotrophic existence means that genes for photosynthesis can be easily discarded . but the loss of photosynthesis can not explain why the plastomes of heterotrophs are so often depauperate in noncoding dna . if plastid genomes from photosynthetic taxa can span the gamut of compactness , why ca n't those of nonphotosynthetic species ? well , recently we showed that they can . the free - living , heterotrophic green alga polytoma uvella has a plastid genome boasting more than 165 kilobases of noncoding dna , making it the most bloated plastome yet found in a heterotroph . in this addendum to the primary study , we elaborate on why the p. uvella plastome is so inflated , discussing the potential impact of a free - living vs. parasitic lifestyle on plastid genome expansion in nonphotosynthetic lineages .

neurogenic pulmonary edema ( npe ) is a fatal complication of severe insults to the central nervous system.1,2 it is proposed that neurogenic pulmonary edema is a functional disturbance provoked by adverse stimuli from outside the lungs and that in the rat , the pulmonary afferent fiber is essential to the production of this edema.3 autonomic nervous dysfunction , possibly sympathetic nerve over - excitation or vagus nerve dysfunction by vagotomy or by lesion of vagal nuclei in the medulla , has been show to induce npe.2 studies involving npe by intracisternal injection of fibrinogen and thrombin have indicated that bilateral vagotomy or the treatment with atropine increased the severity of the edema.4 vagotomy increases the amount of edema for a given degree of pulmonary hypertension.5 vagotomy - induced pulmonary edema has been discussed as neurogenic pulmonary edema . the lungs of vagotomized rats showed alveolar edema.6 blood volume and hematocrit reading became considerably reduced during the development of acute pulmonary edema caused by bilateral cervical vagotomy , depending on whether pulmonary hemorrhage occurs as a complication of the edema and congestion.7 since 1966 , it has been proposed that bilateral interruption of afferent impulses of the tenth cranial nerve is the factor that initiates vagotomy - induced lung edema.8 a subsequent observation concluded that vagal capsaicin - sensitive nerves wielded an inhibitory effect on the development of fibrin injection into the cisterna magna - induced pulmonary edema.9 it was proposed that an unknown neurotransmitter released from capsaicin - sensitive nerves may participate in increasing the lung vascular permeability caused by sympathetic nerve stimulation and that norepinephrine may also play a role in the regulation of permeability through alpha- and beta - adrenoceptors.10 it has been recognized that the main site of nitric oxide ( no ) production in the circulatory system is in the lungs.11 no is produced by a group of enzymes known as nitric oxide synthases ( nos ) . three isoforms of nos have been identified , including two constitutive forms : neuronal ( nnos ) and endothelial ( enos ) , and an inducible form ( inos ) . no is a potent vasodilator in bronchial circulation and may play an important role in regulating airway blood flow excess amounts of no may cause hypotension associated with sepsis , and decreased no levels within the lungs may contribute to the pathologic states associated with pulmonary hypertension . no may also play a critical role in ventilation - perfusion coupling in the lung . this theory is supported by the fact that endogenous no levels in the lung change rapidly in direct proportion to inspired oxygen.12 no has been related to pulmonary edema of various etiologies . pulmonary exhaled no was lower in mountaineers prone to high - altitude pulmonary edema than in those resistant to this condition.13,14 reduced exhaled no may be as a result of altered pulmonary no synthesis and/or transport and clearance , in line with the hypothesis that , in these subjects , a defect in pulmonary epithelial no synthesis may contribute to exaggerated hypoxic pulmonary vasoconstriction and , in turn , to pulmonary edema.13 it was also observed that susceptible subjects have decreased nitrate - nitrite concentrations in bronchoalveolar fluid at high altitude , while resistant subjects have increased concentrations , further supporting a critical role for endogenous no production in maintaining lower pulmonary vascular resistance.15 l - arginine , a no synthase substrate , and n - nitro - l - arginine ( l - nna ) , a no synthase inhibitor , prevented and aggravated , respectively , the increase in pulmonary vascular permeability induced by radiologic contrast medium at high doses , in rats.16 pretreatment with nos inhibitors , such as n - nitro - l - arginine methyl ester ( l - name ) , aminoguanidine and dexamethasone , significantly reduced endotoxin - induced pulmonary edema . overproduction of no was considered detrimental to the lung and exerted toxic effects on the pulmonary endothelial layer.11 however , the involvement of no in npe has not yet been evaluated . the main objective of this study was to evaluate the involvement of peripheric no and its enzymatic production in rats with vagotomy - induced pulmonary edema , by assessing the participation of the cnos and inos pathways in this mechanism . to this end , some animals were pretreated with l - name , a cnos inhibitor , and others with aminoguanidine , a relatively specific inos inhibitor . experimental protocols were performed in accordance with the guide for the care and use of laboratory animals and the ethical principles for animal experimentation , established by the brazilian committee for animal experimentation ( cobea ) , and in accordance with the animal experimentation ethics committee of the state university of londrina ( ceea / uel ) . adult male wistar rats ( n = 167 ) , weighing 250320 g , were distributed into 14 groups : c control animals ( n = 14 ) ; v vagotomized animals ( n = 14 ) ; cl 0.3 ( n = 11 ) ; cl 3.0 ( n = 11 ) ; cl 39 ( n = 11)control animals pretreated with 0.3 mg / kg , 3.0 mg / kg or 39.0 mg / kg l - name , respectively ; vl 0.3 ( n = 14 ) ; vl 3.0 ( n = 9 ) ; vl 39 ( n = 8)vagotomized animals pretreated with 0.3 mg / kg , 3.0 mg / kg or 39.0 mg / kg l - name , respectively ; ca 5 ( n = 11 ) ; ca 10 ( n = 11 ) ; ca 20 ( n = 11)control animals pretreated with 5.0 mg / kg , 10.0 mg / kg or 20.0 mg / kg aminoguanidine , respectively ; va 5 ( n = 14 ) ; va 10 ( n = 14 ) ; va 20 ( n = 14)vagotomized animals pretreated with 5.0 mg / kg , 10.0 mg / kg or 20.0 mg / kg aminoguanidine , respectively . pretreatment consisted of an intravenous injection of l - name or aminoguanidine 10 minutes before surgery . the drugs utilized in this study were : n(g)-nitro - l - arginine methyl ester , l - name ( rbi ) and aminoguanidine ( sigma co. , st louis , mo , usa ) . in controls and vagotomized rats , the vagus nerve was identified and separated from the common carotid artery . in vagotomized animals , those that died during this period were noted , along with their time of death . survivors were sacrificed , under ether anesthesia by severing the inferior vena cava and draining the blood . after the animals ' death , the trachea was cannulated in order to observe tracheal fluid and to classify the severity of pulmonary edema . by way of thoracic incision , lungs were removed and weighed to evaluate pulmonary weight gain and edema index . the severity of pulmonary edema was graded by a method proposed by hamdy et al . , with modifications.17 the edema was graded from 0 to 2 , according to the presence of fluid in the trachea , with 0 for none and 2 for severe . when edema fluid spontaneously appeared in the tracheal tube after opening the chest , the edema was classified as grade 2 . if fluid appeared in the tracheal tube only when the lungs were gently pressed , the edema was grade 1 . when edema fluid did not appear at all , even under gentle pressure , the grade was 0 . as previously proposed , edema was evaluated from the ratio of pulmonary weight : body weight ( 100xpw / bw ) ; this ratio is still in use as the edema index.18 differences between means and the se were examined for significance by anova , followed by tukes multiple comparison test . survival time was examined by student 's t - test , comparing each pair of control to vagotomized animals , vagotomized to vagotomized pretreated with drugs and the pairs of control and vagotomized animals pretreated with drugs . experimental protocols were performed in accordance with the guide for the care and use of laboratory animals and the ethical principles for animal experimentation , established by the brazilian committee for animal experimentation ( cobea ) , and in accordance with the animal experimentation ethics committee of the state university of londrina ( ceea / uel ) . adult male wistar rats ( n = 167 ) , weighing 250320 g , were distributed into 14 groups : c control animals ( n = 14 ) ; v vagotomized animals ( n = 14 ) ; cl 0.3 ( n = 11 ) ; cl 3.0 ( n = 11 ) ; cl 39 ( n = 11)control animals pretreated with 0.3 mg / kg , 3.0 mg / kg or 39.0 mg / kg l - name , respectively ; vl 0.3 ( n = 14 ) ; vl 3.0 ( n = 9 ) ; vl 39 ( n = 8)vagotomized animals pretreated with 0.3 mg / kg , 3.0 mg / kg or 39.0 mg / kg l - name , respectively ; ca 5 ( n = 11 ) ; ca 10 ( n = 11 ) ; ca 20 ( n = 11)control animals pretreated with 5.0 mg / kg , 10.0 mg / kg or 20.0 mg / kg aminoguanidine , respectively ; va 5 ( n = 14 ) ; va 10 ( n = 14 ) ; va 20 ( n = 14)vagotomized animals pretreated with 5.0 mg / kg , 10.0 mg / kg or 20.0 mg / kg aminoguanidine , respectively . pretreatment consisted of an intravenous injection of l - name or aminoguanidine 10 minutes before surgery . the drugs utilized in this study were : n(g)-nitro - l - arginine methyl ester , l - name ( rbi ) and aminoguanidine ( sigma co. , st louis , mo , usa ) . in controls and vagotomized rats , the vagus nerve was exposed through a midline incision in the neck . the vagus nerve was identified and separated from the common carotid artery . in vagotomized animals , all animals were observed for 120 minutes . those that died during this period were noted , along with their time of death . survivors were sacrificed , under ether anesthesia by severing the inferior vena cava and draining the blood . after the animals ' death , the trachea was cannulated in order to observe tracheal fluid and to classify the severity of pulmonary edema . by way of thoracic incision , lungs were removed and weighed to evaluate pulmonary weight gain and edema index . the severity of pulmonary edema was graded by a method proposed by hamdy et al . , with modifications.17 the edema was graded from 0 to 2 , according to the presence of fluid in the trachea , with 0 for none and 2 for severe . when edema fluid spontaneously appeared in the tracheal tube after opening the chest , the edema was classified as grade 2 . if fluid appeared in the tracheal tube only when the lungs were gently pressed , the edema was grade 1 . when edema fluid did not appear at all , even under gentle pressure , the grade was 0 . as previously proposed , edema was evaluated from the ratio of pulmonary weight : body weight ( 100xpw / bw ) ; this ratio is still in use as the edema index.18 differences between means and the se were examined for significance by anova , followed by tukes multiple comparison test . survival time was examined by student 's t - test , comparing each pair of control to vagotomized animals , vagotomized to vagotomized pretreated with drugs and the pairs of control and vagotomized animals pretreated with drugs . our data showed that vagotomy promoted the development of pulmonary edema , as , in the vagotomized rats , the pulmonary weight ( g ) ( 2.600.31 ) and edema index ( 0.940.10 ) were higher than the pulmonary weight ( g ) ( 1.500.06 ) and edema index ( 0.540.01 ) of the control animals ( figures 1 and 2 ) . among vagotomized rats ( n = 14 ) , four animals died during the experimental period ( figure 3 ) and five animals developed grade 2 edema ( tables 1 and 2 ) . the effects observed in vagotomized animals pretreated with l - name varied according to the dose ( figure 1 ) . the highest dose , 39 mg / kg , reduced the edema index ( 0.580.02 ) and no animal in the group vl39 suffered edema grade 2 ( table 1 ) . on the other hand , at the lowest dose , 0.3 mg / kg , the pulmonary weight ( g ) ( 2.970.28 ) and edema index ( 1.000.10 ) remained high and , out of the 14 animals in the group vl0.3 , 6 had edema grade 2 ( table 1 ) . the dose of 3.0 mg / kg promoted intermediate effects between the other two doses ( figure 1 ) . treatment with 39 mg / kg also prolonged the survival of the animals while , in the group pretreated with 0.3 mg / kg l - name , eight rats died during the observation period ( figure 3a ) . the results observed in control animals treated with l - name or with aminoguanidine were similar to those in the control animals without treatment . all three doses of aminoguanidine treatment reduced the pulmonary weight , the edema index and the edema grade in vagotomized rats ( figure 2 and table 2 ) . the objective of the present study was to assess the involvement of no pathways in the development of pulmonary edema . it was observed that the largest dose of l - name inhibited the development of pulmonary edema induced by vagotomy in the group vl39 and prolonged the survival of those animals , while the smallest dose did not promote the same effects . on the other hand , treatment with aminoguanidine , regardless of the dose administered , inhibited the development of the edema . our data suggest that no production from inos is involved in the pulmonary edema induced by vagotomy and , on the contrary , no derived by cnos seems to have protective effects against this type of edema . in rats , the vagus nerve and the sympathetic trunk are anatomically adjacent . hence , in the vagotomy performed in the present study , the sympathetic branch could be damaged , too . in early studies of pulmonary edema following vagotomy it was shown that when the midcervical vagosympathetic trunk in guinea pigs was severed , bilateral interruption of afferent impulses of the tenth cranial nerve was the factor that initiated lung edema.8 this edema was developed in artificially ventilated guinea pig,19 and tracheotomy had no demonstrable effect in vagotomized rats submitted to moderate pulmonary congestion.7 the observation that edema induced by fibrinogen and thrombin was increased by bilateral vagotomy , or by treatment with atropine , indicates that efferent cholinergic fibers in the vagus nerve may play a role in lowering the severity of pulmonary edema.4 in a subsequent experiment involving the use of capsaicin , it was observed that afferent vagal impulses could exert an inhibitory effect on the development of fibrin - induced npe.9 moreover , it was observed that pretreatment with atropine attenuated pulmonary edema in spinal cord - injured rats.20 a hypothesis was introduced that early administration of high atropine doses can prevent npe development on the basis of the attenuation of heart rate decrease , which was recognized as an important factor of neurogenic pulmonary edema formation.21 in rats , bilateral vagotomy increased the incidence of npe.17 the rats that suffered vagotomy in our study developed a higher pulmonary edema index than the controls . among vagotomized rats , similar results were observed in rats treated with a dose of 0.3 mg / kg of l - name , which had a high edema index . although these results represent development of edema , not all animals showed a degree of edema . in our opinion , this is because of the fact that the rats were observed for a period of only 120 minutes and not until death , when more animals would possibly have developed edema . the establishment of an observation period followed by sacrifice of those who survived could also justify the degree of variance observed in the results presented . the incidence of pulmonary edema in rats promoted by intracisternal injection of fibrinogen and thrombin associated with vagotomy was related to the high ( 25 mg / kg or 50 mg / kg ) doses of pentobarbital anesthesia.4 it was later observed that neurogenic pulmonary edema in rats was more pronounced in pentobarbital - anesthetized ( 60 mg / kg ) rats compared with xylazine - ketamine anesthesia22 and that it developed in rats anesthetized with 1.5% isoflurane , but not in those anesthetized with 3% isoflurane,20 illustrating that anesthetic drugs used in experimental neurogenic pulmonary edema may be an important factor in the genesis of edema . in the present study npe has been also associated with pulmonary vascular permeability.17 concerning the mechanism of involvement of no in the maintenance of liquid balance in isolated rabbit lung , it was found that inhibition of no production with l - name caused a significant increase in the rate of weight gain , while the addition of lodoxamide or 8 br - cgmp attenuated this increase.23 these findings suggest a role for endogenous no in the relaxation of endothelial cells and also in helping to prevent pulmonary edema by stabilizing mast cells . thus , no production mediated by inos has been considered to exert a toxic effect on the pulmonary endothelial layer once l - name ( 10 mg / kg ) , aminoguanidine ( 15 mg / kg ) or dexamethasone ( 3 mg / kg ) all attenuated endotoxin - induced pulmonary edema.11 as inos has been implicated in the pathophysiology of congestive heart failure , it was hypothesized that inos deficiency would reduce the severity of congestive heart failure in mice . however , it was found that deficiency of inos did not significantly affect severe congestive heart failure in mice after myocardial infarction.24 according to the proposed involvement of no produced by inos mediation on pulmonary edema , it was suggested that morphine had a prophylactic effect on -naphthylthiourea - induced lung damage through inhibition of inos expression.18 the results observed in the present study demonstrate that the inhibition of no production through inos promoted an attenuation of vagotomy - induced pulmonary edema . thus , it is likely that , in this experimental model , no produced by inos is involved in the development of pulmonary edema . our group observed a similar result where pulmonary edema induced by endotoxemia was attenuated by aminoguanidine and worsened by l - name in control and exercise - trained animals.25 l - name increases weight gain in isolated perfused rabbit lung . the authors suggested that no had a protective role in the maintenance of normal pulmonary vascular permeability.23 moreover , it was observed that up - regulation of enos is a protective mechanism against inflammatory pulmonary damage following ischemia reperfusion.26 also , the role of no in the development of npe in spinal cord - injured rats was considered protective considering that acute treatment with l - name ( 30 mg / kg ) just before the injury enhanced npe severity.20 however , no data in the literature has studied the involvement of both pathways of no production in neurogenic pulmonary edema . l - name was considered an inhibitor of cnos , however , it may also inhibit inos at a dose of 10 mg / kg.11,27 the treatment of vagotomized rats with 39 mg / kg of l - name promoted a reduction in pulmonary edema , that was statistically different when compared with the group treated with 0.3 mg / kg of l - name , and the treatment with aminoguanidine ( at any dose ) reduced the incidence of pulmonary edema in vagotomized rats , as well as in the animals treated with the highest dose of l - name . our hypothesis is that the non - selective blockade of cnos by administering the highest dose of l - name could also inhibit the inos pathway . thus , cnos appears to participate in the mechanism of pulmonary edema induced by vagotomy , as a protective mechanism . on the other hand

objective : the objective of this study was to evaluate the involvement of peripheral nitric oxide ( no ) in vagotomy - induced pulmonary edema by verifying whether the nitric oxide synthases ( nos ) , constitutive ( cnos ) and inducible ( inos ) , participate in this mechanism.introduction:it has been proposed that vagotomy induces neurogenic pulmonary edema or intensifies the edema of other etiologies.methods:control and vagotomized rats were pretreated with 0.3 mg / kg , 3.0 mg / kg or 39.0 mg / kg of l - name , or with 5.0 mg / kg , 10.0 mg / kg or 20.0 mg / kg of aminoguanidine . all animals were observed for 120 minutes . after the animals ' death , the trachea was catheterized in order to observe tracheal fluid and to classify the severity of pulmonary edema . the lungs were removed and weighed to evaluate pulmonary weight gain and edema index.results:vagotomy promoted pulmonary edema as edema was significantly higher than in the control . this effect was modified by treatment with l - name . the highest dose , 39.0 mg / kg , reduced the edema and prolonged the survival of the animals , while at the lowest dose , 0.3 mg / kg , the edema and reduced survival rates were maintained . aminoguanidine , regardless of the dose inhibited the development of the edema . its effect was similar to that observed when the highest dose of l - name was administered . it may be that the non - selective blockade of cnos by the highest dose of l - name also inhibited the inos pathway.conclusion:our data suggest that inos could be directly involved in pulmonary edema induced by vagotomy and cnos appears to participate as a protector mechanism .

Andrew Zuckerman Jony Ive is himself classic Apple. Brushed steel, polished glass hardware, complicated software honed to simplicity. His genius is not just his ability to see what others cannot but also how he applies it. To watch him with his workmates in the holy of holies, Apple’s design lab, or on a night out is to observe a very rare esprit de corps. They love their boss, and he loves them. What the competitors don’t seem to understand is you cannot get people this smart to work this hard just for money. Jony is Obi-Wan. His team are Jedi whose nobility depends on the pursuit of greatness over profit, believing the latter will always follow the former, stubbornly passing up near-term good opportunities to pursue great ones in the distance. Jony’s values happen to add value — emotional and financial. It takes a unique alchemy of form and function for millions of people to feel so passionately about the robot in their pocket. Bono is a musician and an activist Next Alex Atala ||||| According to multiple people who have either seen or have been briefed on the upcoming iOS 7, the operating system sports a redesigned user-interface that will be attractive to new iOS users, but potentially unsettling for those who are long-accustomed to the platform… The new interface is said to be “very, very flat,” according to one source. Another person said that the interface loses all signs of gloss, shine, and skeuomorphism seen across current and past versions of iOS. Another source framed the new OS as having a level of “flatness” approaching recent releases of Microsoft’s Windows Phone “Metro” UI. “Flat” design is based on simplicity and pushes aside heavy textures and digital metaphors of real-life objects found in skeumorphic interfaces. “Flatness” could also point to a more streamlined interface across the entire system that can stand the test of time. For example, younger generations of iOS users may not resonate well with a yellow notepad (as found in the current iOS Notes app) or the leather-bound calendar app. iOS has typically been regarded as an easy-to-use, intuitive operating system. The Company even seems to say as much on its iOS webpage (shown directly below). With its large user-base and market attraction, Apple obviously does not want to make any design changes that make the software more difficult to use. While the look of the updated system may be surprising to some, iOS 7 is reportedly not more difficult to use than earlier versions of software platform. There is apparently no new learning curve in the same way there was no learning curve when the iPods went color. While iOS 7 does look different, its core apps and system fundamentals (like the Lock and Home screens) mostly operate in a similar fashion to how they do today. iOS 7 is codenamed “Innsbruck,” according to three people familiar with the OS. The interface changes include an all-new icon set for Apple’s native apps in addition to newly designed tool bars, tab bars, and other fundamental interface features across the system. iOS devices running the next-generation software reportedly have polarizing filters to decrease viewing angles of on-lookers. In addition to losing the complex interface design characteristics from earlier versions of iOS, Apple has been discussing and testing ways to add more ‘glance-able’ information and system options panels, like Notification Center, to the software. While it is still uncertain if Apple will end up including such new functionality in iOS 7, or how the Company will implement the potential addition, one of the early ideas was to implement the new panels via swipes from the left and right side of an iOS device’s display. This would be similar to the gesture on Apple’s Mac trackpads for accessing Notification Center in Mountain Lion, but what, specifically, the iOS gesture could access is uncertain. Prior to announcing and launching new versions of iOS, Apple tests many various implementations for features. For example, Apple had toyed with the idea of having an Expose-like Multitasking interface for iOS 4, but ended up choosing the linen-backed bottom drawer that we are now accustomed to. Apple’s redesigned iOS experience stems from Apple Senior Vice President of Industrial Design Jony Ive now spearheading interface design. With former Senior Vice President of iOS Scott Forstall leaving Apple late last year, influence on software design was handed over to Ive. Ive is long-known as the king behind Apple’s many hardware successes like the iPad, iPhone, iPod, and Mac computers. In an interview early last year, Ive shared his lack of connection to the software that runs on his hardware. When I mention the fake stitching, Ive offers a wince but it’s a gesture of sympathy rather than a suggestion that he dislikes such things. At least, that’s how I read it. He refuses to be drawn on the matter, offering a diplomatic reply: “My focus is very much working with the other teams on the product ideas and then developing the hardware and so that’s our focus and that’s our responsibility. In terms of those elements you’re talking about, I’m not really connected to that.” Matching the information about iOS 7 gaining a “flatter” interface design, a profile of Apple’s internal software design work paints Ive as against flashy, skeumorphic interfaces: Inside Apple, tension has brewed for years over the issue. Apple iOS SVP Scott Forstall is said to push for skeuomorphic design, while industrial designer Jony Ive and other Apple higher-ups are said to oppose the direction. “You could tell who did the product based on how much glitz was in the UI,” says one source intimately familiar with Apple’s design process. Apple’s change in interface philosophy under Jony Ive and Tim Cook is also a radical departure from Apple under Steve Jobs. Jobs, according to the same profile of Apple’s design work, was, like Forstall, a proponent of life-like interfaces. But before Forstall, it was Steve Jobs who encouraged the skeuomorphic approach, some say. “iCal’s leather-stitching was literally based on a texture in his Gulfstream jet,” says the former senior UI designer. “There was lots of internal email among UI designers at Apple saying this was just embarrassing, just terrible.” While one of our sources paints the iOS 7 design changes as changes that will gain the appreciation of some and the surprise of others, Apple CEO Tim Cook seems excited and confident about what the company has in store. During the question-and-answer session of the Q1 2013 earnings call, responding to a question regarding Apple’s software updates for 2013, Cook said, “we feel great about what we have got in store.” Based on Cook’s past comments and moves to further integrate both Apple’s products and its internal culture, Cook’s choice to put Ive in charge of software design also seems to stem from Cook’s admiration of integrated experiences. In a wide-ranging interview with Bloomberg BusinessWeek earlier this year, Cook addressed Forstall’s ousting from Apple and Ive’s new work on software design as a way to further unify Apple’s hardware and software: Jony [Ive, senior vice president of industrial design], who I think has the best taste of anyone in the world and the best design skills, now has responsibility for the human interface. I mean, look at our products. (Cook reaches for his iPhone.) The face of this is the software, right? And the face of this iPad is the software. So it’s saying, Jony has done a remarkable job leading our hardware design, so let’s also have Jony responsible for the software and the look and feel of the software, not the underlying architecture and so forth, but the look and feel. Over the past couple of months, Apple seems to have been hinting at an impending shift in its software design philosophy. Earlier this year, Apple released an updated version of its Podcasts app for iPhone and iPad in order to simplify some design elements (comparison shown above). Prior to that recent update, the application included a physical “tape deck” interface for the user to manipulate in order to move through a podcast. Additionally, Apple’s WWDC 2013 logo, the art for the conference in which iOS 7 will be announced, has sparked speculation about flat interface design with its modern, lightweight text and other elements. Indeed, one source claims that Apple’s Game Center icon and interface materials will be somewhat akin to the colorful nature of the WWDC 2013 logo. Because of its casino-like, green-felt design, Apple’s current Game Center app has been widely panned by proponents of flat software interface design. Also, Apple highlights iPad and iPhone applications on its homepage that include flat-interface designs. For example, the home page touting the full-sized iPad and iPad mini highlights former Apple employee Loren Brichter’s popular Letterpress game. Letterpress has been regarded by many as a simple to use, “easy-on-the-eyes” game for its flat textured interface. With Apple’s vibrant iOS application development community, the prospects of a redesigned iOS go beyond Apple’s apps and core interface functions. Internal to the third-party iOS app community, some fear that Apple’s interface changes could deem App Store apps, that are currently built to look consistent with Apple’s own interface, outdated. AppHero’s Jordan Satok, who has a comprehensive view of the App Store ecosystem, points out that iOS interface changes will likely not pose challenges for all developers. “When we started building iOS apps almost 5 years ago, most apps looked the same. Apple did an amazing job designing UIKit to provide a really consistent user experience across apps,” he said. “As the App Store has grown, and the types of apps being built have evolved, designers and developers have pioneered new interface styles and concepts.” Because many apps are picking up unique interface designs, Apple’s changes to its core software will likely not make much of a difference to these developers. Nonetheless, it is likely that once iOS 7 is announced, developers that have followed Apple’s own past iOS design trends will quickly move to enhance their App Store apps to follow some of Apple’s changes. Apple’s next version of OS X will include some design changes, but the changes will not be as notable as the aforementioned enhancements to iOS. ||||| Jonathan Ive, six months into an expanded role as Apple Inc (AAPL).’s top product visionary, has embarked on a sweeping software overhaul that leaves the company at risk of falling behind on a new version of the operating system that runs iPhones and iPads, people with knowledge of the matter said. Already in charge of product design, Ive assumed oversight of the look and feel of software running all Apple electronics in a shakeup by Chief Executive Officer Tim Cook last year that included the departure of software chief Scott Forstall. Ive, 46, has begun revamping iPhone and iPad applications, shunning realistic images, such as wood bookshelves for the Newsstand feature, and he’s exploring more dramatic changes to the e-mail and calendar tools, said the people, who asked not to be identified because the plans are private. Ive is also methodically reviewing new designs, seeking to avoid a repeat of last year’s release of map tools that were widely panned, and he’s encouraging collaboration between the software and hardware divisions, which operated in silos under co-founder Steve Jobs, people said. The introduction of new features, along with an emphasis on cooperation and deliberation, comes at a cost for Cupertino, California-based Apple. Engineers are racing to finish iOS 7, the next version of the mobile software, in time for a June preview at Apple’s annual Worldwide Developers Conference. Photographer: Kimberly White/Bloomberg Steve Jobs told his biographer Walter Isaacson that Ive was his “spiritual partner” at Apple to whom he gave more operational power than anybody at the company. Close Steve Jobs told his biographer Walter Isaacson that Ive was his “spiritual partner” at... Read More Close Open Photographer: Kimberly White/Bloomberg Steve Jobs told his biographer Walter Isaacson that Ive was his “spiritual partner” at Apple to whom he gave more operational power than anybody at the company. While the company still expects to release iOS 7 on time as soon as September, internal deadlines for submitting features for testing are being set later than past releases, people said. ‘Tremendous Pressure’ Staff from Apple’s Mac team have also been roped in to help the mobile-software group finish the job, people said. Apple has made similar moves in the past, including with the first version of iOS in 2007. “Apple is really under tremendous pressure to come out with something different and something new,” said Greg Sterling, an analyst at Opus Research in San Francisco. Ive has “a tremendous sense of design, and he’s been the guru behind a lot of these enormously successful products, but he’s always had someone like a Jobs to push back on him and give him some guidance, and it’s not clear that Tim Cook is capable of playing that role. Maybe without a collaborator, he’s not as strong.” Another possibility is that Apple’s next upgrade isn’t as robust or feature-rich as projected, and some changes come in future releases. Photographer: Simon Dawson/Bloomberg Apple hasn’t changed the look of many mobile-software programs like e-mail since the iPhone was introduced in 2007. Close Apple hasn’t changed the look of many mobile-software programs like e-mail since the... Read More Close Open Photographer: Simon Dawson/Bloomberg Apple hasn’t changed the look of many mobile-software programs like e-mail since the iPhone was introduced in 2007. ‘Spiritual Partner’ Ive has a storied place in Apple’s history. After Jobs returned as CEO in 1997, Ive’s design of the iMac helped the company regain its footing after nearly falling into bankruptcy. Jobs told his biographer Walter Isaacson that Ive was his “spiritual partner” at Apple to whom he gave more operational power than anybody at the company. Ive is widely credited with working with Jobs to create the company’s most famous products, including the iPod, iPhone and iPad. Even so, his specialty has been hardware, designing a product out of materials like aluminum and glass -- not software, which is based in code. He also has shunned the spotlight, rebuffing overtures to figure more prominently at product events. Seeing Ive around Apple’s campus was akin to a celebrity sighting, according to a former manager. It’s not clear that Ive will be as effective as Jobs in getting teams to finish projects on time. Cook elevated Ive in October, seeking to end clashes between Forstall and other senior managers that flared in the wake of the death of former CEO Jobs, people with knowledge of the matter said at the time. Tim’s ‘Challenge’ The strife made it harder for teams to work together and threatened Apple’s ability to keep producing the types of electronics that made it the most valuable company in the world. An operations expert who built Apple’s vast supply chain, Cook opted to leave the minutiae of product design to Ive amid intensifying competition from Samsung Electronics Co. (005930) and Google Inc. (GOOG) “Tim is a supply-chain expert and he needs to rely on people like Jony to be able to make the right decisions,” said David Yoffie, a professor at Harvard Business School in Boston. “That doesn’t mean things run smoothly -- because a challenge for Tim not being involved in the detailed product discussions is making sure that gridlock is avoided and decisions are made.” The management shuffle in October tapped the brakes on work on the upgrade to iOS 7. New features typically submitted for testing around February ran a month or more behind schedule, according to one of the people with knowledge of the matter. ‘Tidying’ Needed Software design involves the graphical style of images on the screen, as well as the deeper experience of how a user progresses through a given task, such as the steps needed for deleting an e-mail or entering a calendar item. Apple hasn’t changed the look of many mobile-software programs like e-mail since the iPhone was introduced in 2007. Social-networking features are limited, and applications don’t always work well together, said Benedict Evans, an analyst at Enders Analysis in London. “There is a tidying up that needs to be done and a rethinking,” he said. On top of that, Ive is moving the company away from layered and literal -- or skeuomorphic -- design elements, toward ones that are intended to give the software a flatter design that’s more unified and less cluttered, according to people familiar with the changes. Bigger shifts, to such features as e-mail, may not even be ready this year and may be introduced in future releases, people said. Gesture Control Longer term, Ive also has shown interest in altering how people control their computers. He has met with makers of gesture technology that lets people navigate their gadgets by moving their hands -- without touching the screen, said a personal familiar with those interactions. “If the hardware is going to stay minimalist and reduced, I would say the next step would be to look at three-dimensional interfaces,” said Ross Lovegrove, an industrial designer who has worked with such companies as Apple and Sony Corp. For now, the priority is getting mobile software done in time for the next iPhone, due to be released as soon as September. The rush to finish the software running on more than 500 million iPhones, iPads and iPod Touches underscores how decision-making has slowed under the current leadership team. Collaboration Emphasis While Jobs would force through ideas that he wanted the company to prioritize, Cook has emphasized collaboration. The internal debates are leading to a more deliberate approach for product and marketing decisions, according to a person at a company that does business with Apple. Ive’s expanded influence comes at a critical time for Apple. Investors are anxious to see what new products the company will debut without Jobs’s leadership and as Samsung and Google improve their mobile products -- and hire Apple’s employees to do it. One Apple engineer who left last year said he was quickly contacted by Samsung to invite him in to talk about ways the Suwon, South Korea-based electronics giant can improve its software. Google recently hired Steve Sinclair, a veteran iOS marketing manager, for its Motorola unit. “The bar for good design has been raised and Apple is facing fiercer competition,” said Sarah Rotman Epps, an analyst at Forrester Research (FORR). Town Hall The stock fell less than 1 percent to $439.29 at the close in New York. Apple shares have climbed 8.2 percent since April 23, when Cook announced plans for the largest share buyback in corporate history. Even so, Apple remains under pressure to deliver a new breakthrough hit amid slowing growth and a stock-price slump that has wiped out more than a third of its value since a September peak. Ive’s expanded role was on display in March when he led a more than two-hour town-hall meeting at the De Anza 3 auditorium in Cupertino. Cook sat listening as Ive spoke at length about the shifts under way, said two people familiar with the gathering. For Ive, oversight of software design is a shift. Throughout his two decades at Apple, he has kept mostly to the small group of about 15 people working in secret to refine prototypes of future hardware products. He rarely interacted with the software designers led by former mobile-software head Forstall, who had been similarly clandestine. To end those fissures, Ive now attends meetings with the software design group along with its leader, Greg Christie, to offer feedback. Rich Interface He has listened respectfully in those sessions and has been careful not to try to force through his ideas, this person said. He also is giving them an earlier look at what future hardware products will look like, one person said. “Jony Ive isn’t a coder, but he clearly understands the value and importance of a rich, easy-to-use interface and he will have great input on that,” said Tim Bajarin, a technology-industry analyst with Creative Strategies. The Wall Street Journal previously reported Ive’s involvement in the software meetings. While the exact changes Ive is implementing to Apple’s mobile software remain secret, they are significant enough that those with test versions have a special film over their iPhone screens to obstruct what others can see, one person said, a detail previously reported by the website Daring Fireball. Cook’s decision to give new responsibilities to Ive is a natural evolution for the designer. “Tim Cook understands that they need one individual with that eye for design to oversee both the hardware and the software,” Bajarin said. To contact the reporter on this story: Adam Satariano in San Francisco at [email protected] To contact the editor responsible for this story: Tom Giles at [email protected]

– Apple's next mobile operating system, iOS 7, is supposed to be in the sweaty palms of Mac fanboys as early as September. But—at least within the company—deadlines are being pushed back as the company's new design visionary, Jonathan Ive (who recently made the Time 100 list), makes big overhauls to the look of the software, Bloomberg reports. Many of the iOS logos and programs haven't changed aesthetically since the iPhone was released in 2007. Insiders say the new look will be less shiny and glossy, and rely less on "skeuomorphs" (designs made to imitate their real-world counterparts, like the wooden shelves on the Newsstand app, or the radio mic on Voice Memos), in favor of the "flat" look employed by Microsoft on its Windows Phone, 9to5Mac says. But while the look might be different, the ease of use is not—9to5Mac says there's no learning curve involved in the new iOS.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Urban Jobs Act of 2010''. SEC. 2. FINDINGS AND PURPOSE. (a) Findings.--Congress finds the following: (1) One-third of minority youth are unemployed. (2) The labor force participation rate for persons without a high school diploma is 20 percentage points lower than the labor force participation rate for high school graduates. (3) Nationally, approximately 70 percent of all students graduate from high school, but African-American and Hispanic students have a 55 percent or less chance of graduating from high school. (4) High school dropouts from the class of 2004 will cost the Nation more than $325 billion in lost wages, taxes, and productivity over their lifetimes. (5) Only 52 percent of students in the 50 largest cities in the United States graduate from high school. That rate is below the national high school graduation rate of 70 percent, and also falls short of the 60 percent average for urban districts across the Nation. (6) Over his or her lifetime, a high school dropout earns, on average, about $260,000 less than a high school graduate, and about $1 million less than a college graduate. (7) Approximately 75 percent of State prison inmates and 59 percent of Federal prison inmates have not completed high school. Increasing the high school completion rate by 1 percent for all men ages 20 to 60 would save the United States $1.4 billion annually in reduced costs associated with crime. (8) According to a recent study, a 10 percent increase in the male high school graduation rate would reduce arrest rates for murder and assault by about 20 percent, motor vehicle theft by 13 percent, and arson by 8 percent. (9) The National Urban League is a historic civil rights organization dedicated to economic empowerment in order to elevate the standard of living in historically underserved urban communities. Founded in 1910 and headquartered in New York City, the National Urban League spearheads the efforts of its local affiliates through the development of programs, public policy research, and advocacy. (10) There are more than 100 local affiliates of the National Urban League located in 36 States and the District of Columbia, providing direct services that impact and improve the lives of more than 2 million people nationwide. Local National Urban League affiliates operate programs that focus on education, job training and placement, housing, business development, and many other important initiatives. (11) The National Urban League has a history of success in implementing national programs through its local affiliate network. From 2007 to 2010, 27 local National Urban League affiliates served at-risk young adults by providing job skills training, community service opportunities, and employment for over 3,500 young adults ages 18 to 24. (b) Purpose.--It is the purpose of this Act to provide adequate resources for the National Urban League (acting through local National Urban League affiliates) to reduce the disproportionate incarceration of minority youth and to prepare eligible young adults for entry into the world of work by providing a comprehensive set of services that includes job training, education, and support services. SEC. 3. URBAN JOBS PROGRAM. (a) In General.--Subtitle D of title I of the Workforce Investment Act of 1998 (29 U.S.C. 2911 et seq.) is amended-- (1) by redesignating section 174 as section 175; (2) in section 173, by striking ``174'' each place it appears and inserting ``175''; and (3) by inserting after section 173A the following: ``SEC. 174. URBAN JOBS PROGRAM. ``(a) Program Authorized.-- ``(1) In general.--The Secretary of Labor may make grants to the National Urban League for the purpose of operating an Urban Jobs Program through local National Urban League affiliates. ``(2) Use of funds.--Funds from a grant made under paragraph (1) shall be used by the National Urban League to provide a comprehensive set of services and activities for eligible young adults, to be implemented by local National Urban League affiliates. Services and activities eligible for assistance include the following: ``(A) Case management services to help program participants effectively use the activities and services offered under the program. ``(B) Educational offerings, including skill assessment, reading and math remediation, educational enrichment, General Education Development credential preparation, and post-secondary education. ``(C) Employment and job readiness activities, including mentoring, placement in community service opportunities, internships, on-the-job training, occupational skills training, job placement in unsubsidized jobs, and personal development. ``(D) Support services, including health and nutrition referral, housing assistance, training in interpersonal and basic living skills, transportation, child care, clothing, and other assistance as needed. ``(3) Report.-- ``(A) In general.--Not later than May 1 of each fiscal year for which amounts are made available to carry out this section, the Secretary shall submit to Congress a report regarding-- ``(i) the progress made under this section by the National Urban League and local National Urban League affiliates in implementing the program; and ``(ii) the effectiveness of the program in improving General Educational Development credential attainment and job placement in unsubsidized jobs for program participants. ``(B) Inapplicability of section 172.--The program shall not be subject to evaluations required under section 172. ``(b) National Jobs Council Advisory Committee.-- ``(1) Establishment.--The Secretary shall establish a committee to be known as the National Jobs Council Advisory Committee. ``(2) Duties.--The committee shall advise the Secretary concerning-- ``(A) the design and operation of the program; ``(B) long-term strategic priorities for the program; and ``(C) the formulation and application of guidelines related to activities carried out under the program. ``(3) Membership.--The committee shall be comprised of 11 members, to be appointed by the Secretary as follows: ``(A) 3 individuals from the private sector who are senior human resources or diversity executives with national or regional responsibilities and experience in oversight that includes hiring, employee training, or employee relations. ``(B) 5 representatives of employers in high- impact, high-growth industries, as defined by the Secretary. ``(C) 1 National Urban League Workforce Development staff member. ``(D) 2 representatives from the Department of Labor. ``(c) Sense of Congress Regarding Local Advisory Committees.--It is the sense of Congress that a local National Urban League affiliate receiving funding under this section should establish a local jobs council advisory committee, the membership of which should include representatives from not fewer than 5 employers from high-growth industries in the locality, to aid in establishing support from the local community for and guiding the local implementation of the program. ``(d) Funding.-- ``(1) Authorization of appropriations.--There is authorized to be appropriated to carry out this section-- ``(A) $20,000,000 for fiscal year 2011; ``(B) $30,000,000 for fiscal year 2012; ``(C) $40,000,000 for fiscal year 2013; ``(D) $50,000,000 for fiscal year 2014; and ``(E) $60,000,000 for fiscal year 2015. ``(2) Limitation.--Not more than 2 percent of funds appropriated for any fiscal year under paragraph (1) may be used for expenses associated with carrying out the requirements of subsection (b). ``(e) Definitions.--In this section: ``(1) Eligible young adults.--The term `eligible young adults' means individuals ages 18 to 24 who-- ``(A) are not enrolled in secondary or post- secondary school; or ``(B) are or have been subject to any stage of the criminal justice process. ``(2) Program.--The term `program' means the Urban Jobs Program established under subsection (a). ``(3) Unsubsidized job.--The term `unsubsidized job' means employment for which the wages are provided by an employer that does not receive public funds for the creation and maintenance of the employment position.''. (b) Conforming Amendment.--The table of contents contained in section 1(b) of such Act is amended-- (1) by inserting a period at the end of the item relating to section 173A; and (2) by striking the item relating to section 174 and inserting the following: ``Sec. 174. Urban jobs program. ``Sec. 175. Authorization of appropriations.''.

Urban Jobs Act of 2010 - Amends the Workforce Investment Act of 1998 to authorize the Secretary of Labor to make grants to the National Urban League to operate, through local affiliates, an Urban Jobs Program to provide job training, education, and support services and activities for eligible young adults to prepare them for entry into the workforce. Defines "eligible young adults" as individuals ages 18 to 24 who: (1) are not enrolled in secondary or post-secondary school; or (2) are or have been subject to the criminal justice process. Directs the Secretary to establish a National Jobs Council Advisory Committee. Expresses the sense of Congress that National Urban League affiliates should establish local jobs council advisory committees to aid in establishing local community support for local implementation of the program.

the introduction of whole body positron emission tomography ( pet ) using [ f]fluorodeoxyglucose ( fdg ) in the 1980s for localization of colon metastasis has led to significant advances in nuclear medicine and oncology enabling more differentiation between benign and malignant processes on other imaging modalities and helping detect more occult metastases . this technology is based on the principle of increased glucose consumption by the tumor cells and the ability to detect the photon produced by the breakdown of [ f]fdg inside the cancer cells . currently , the applications of this technology have broadened to include a large number of tumors such as melanoma , lung cancer , gastrointestinal stromal tumor , lymphoma , head and neck tumors , thyroid cancer , colon cancer , breast cancer , stomach cancer , pancreatic cancer , esophageal cancer and others to confirm the extension of the tumor , cancer recurrence and to follow up the response of chemotherapy with excellent sensitivity and specificity . in parallel , surgeons are often asked to biopsy or remove an fdg avid lesion in an effort to analyze the nature of the lesion , restage , check for possible tumor recurrence or even prolong survival . however , those lesions are not always easily detectable on the other imaging modalities and localizing findings identified by an abnormal pet / ct scan in a heavily scarred surgical field can be challenging . low energy gamma probes ( 140 kev ) routinely used for sentinel node biopsy procedures are not capable of detecting the high energy rays of 511 kev emitted by fdg . recent technological developments have led to the production of a high energy gamma probe ( pet probe ) that can be used to guide surgery in those difficult areas of the body . this article describes our experience localizing and removing fdg avid lesions in the head and neck , chest , abdomen and retroperitoneum . the patients medical history , imaging studies and clinical indications were carefully reviewed and discussed for all cases . initially , initial detection of fdg avid lesions was considered sufficient for surgical intervention , however , thereafter and in most cases , persistence of fdg avidity on a minimum of two sequential studies was required before surgical intervention . all patients were injected with 1012 mci of fdg 34 h prior to the procedure . intra - operatively , the lesions were localized using a pet probe ( intramedical imaging / ge , california ) for navigation . all localized lesions were removed confirming the fdg activity outside the body and a final background count was obtained in the tumor bed . the final pathologic reading of the lesions , and any operative and post - operative complications were recorded . nine patients underwent surgical intervention with the intra - operative use of the pet probe to navigate and localize previously identified fdg avid lesions . the underlying cancer diagnosis , pet findings , operative results and follow - up are presented in table 1 . in all cases except one , the surgical field had undergone previous surgery , radiotherapy , heavy chemotherapy or a combination of those ( table 2 ) . table 1diagnosis , pet ct findings , operative results and follow-up.patientdiagnosispet findingsoperative resultfollow - up1gastric cancer1 lesion porta hepatis1 lesion removed15 months ned2melanoma4 lesions right neck4 lesions removed7 months awd3melanoma1 lesion left axillanegative pet54 months ned4melanoma2 lesions retroperitoneum2 lesions removed10 months ned5breast cancer2 lesions left axilla2 lesions removed16 months dod6breast cancer1 lesion left interpectoral area1 lesion removed33 months awd7breast cancer1 lesion left subclavicular1 lesion removed7 months ned8lymphoma1 lesion right axilla1 lymph node removed12 months ned9lymphoma1 lesion right groin1 lymph node removed7 months ned10suspected lymphoma1 lesion right axillanegative petlostawd , alive with disease ; dod , dead of disease ; ned , no evidence of disease . table 2surgical field.patientsurgeryradiationchemotherapy1+2+34+5++6++7++8+ ( scarred nodes)9+ ( scarred nodes)10 diagnosis , pet ct findings , operative results and follow - up . awd , alive with disease ; dod , dead of disease ; ned , no evidence of disease . the first patient had undergone a subtotal gastrectomy with lymphadenectomy 20 months before the pet probe guided surgery . a few months after surgery pet / ct revealed a single fdg avid lesion in the porta hepatis . the patient was treated with chemotherapy and radiation , however the lesion grew slowly on follow up pet / ct without evidence of additional lesions . at surgery , a metastatic lymph node was found on the hepatic artery and removed . at 9 months all patients had wide local excision of their melanoma and clearance of their lymph nodes . the second patient had a lesion removed from his right ear with negative sentinel nodes 5 years previously with recurrence in the parotid gland and in the neck after 4 years treated with a parotidectomy and neck dissection . a follow - up pet scan a year later , found 4 lesions in the right neck . all 4 lesions were identified intra - operatively with the pet probe and removed . at 18 months the third patient had a melanoma removed from his upper back and bilateral neck dissections , 4 years previously . this lesion was not identified with the pet probe and no tissue was removed . at 48 months the fourth patient had a melanoma removed from his right foot 5 years before the pet guided intervention . he experienced a few episodes of in transit recurrences on his right leg but was free of disease 24 months before a pet scan identified 2 lesions in the retroperitoneum . at 4 months the patient was free of disease for 17 months and at 27 months is alive with new fdg avid lesions in the mediastinum . the seventh and eight patients were diagnosed with lymphoma previously and were treated but in a follow - up pet scan were found to have fdg avid lesions in the right axilla and in the right groin , respectively . both patients underwent exploration with pet probe guidance ; in both cases no recurrence was found in the fdg avid node . the last patient had a positive pet scan in the right axilla with a core needle biopsy suspicious for lymphoma . the pet scan on the day of surgery did not show the lesion and this was confirmed in the operating room where no activity was detected by the pet probe . advances in medicine in general and in surgery in particular are closely related to advances in technology . progress in technology opens new horizons and new opportunities to explore the merit of procedures that would not otherwise be possible . the clinical scientist plays a key role in the development and investigation of the indications and procedures within the clinical knowledge and management of the disease process . in 1994 , described the intra - operative used of a beta probe able to detect the 511 kev photons derived from radioactive decay of f left free inside the tumor cell after phosphorylation of the attached glucose molecule . the development of high energy gamma probes by haigh et al . in 2000 and raylman et al . in 2001 with excellent sensitivity in detecting [ f]fdg avid lesions initiated the era of pet probe guided surgery for removal of occult lesions and lesions in re - operative scarred tissues . [ f]fdg enters the tumor cells using facilitative glucose transporters ( glucose transporter-1 ) and undergoes phosphorylation to phosphodeoxyglucose ( pdg)-6 by hexokinase , which accumulates in the tumor cells secondary to a slow dephosphorylation . the f molecule is released and its radioactive decay produces two 511 kev photons traveling at 180 from each other . the detection of these photons is the basis of the pet scan and high energy gamma probes . intra - operative detection of [ f]fdg avid metastatic and recurrent lesions is the main application of radio guided surgery using pet probes . this concept applies particularly to the exploration and localization of these lesions in highly scarred tissue from re - operation or secondary to radiotherapy . the localization of occult lesions not seen by any of the other available imaging studies is another indication when lesions are particularly enhanced using pet probes , which can guide the surgeon to lesions not easily visualized or palpated . in this study we describe our experience localizing and removing fdg avid lesions in the head and neck , chest , abdomen and retroperitoneum . it is important to notice the accuracy of localizing the fdg avid lesion once the pet scan confirms their presence . from 14 lesions seen in pet / ct the two lesions that were not identified also had negative pet scans on the day of surgery . the intra - operative accuracy of pet probe finding fdg avid lesions approximates 100% . in our experience , the probe was very helpful navigating into scar tissue and confirming complete removal of the lesions after the tumor bed activity reached the background counts . as can be seen from the results , on two occasions , mostly at the beginning of our experience , the fdg injection on the day of the surgery did not confirm the presence of an avid lesion . for that reason our recommendation is to confirm the presence of fdg avid lesions on at least two sequential pet scans . the next question is how to select the patients who would benefit from pet probe guided removal of metastatic lesions . we have tried to adhere to the general principles guiding the indications for surgical removal of metastatic lesions . only patients who could potentially be rendered disease free and who could benefit from improved survival were offered the procedure . in some cases , as with the gastric cancer patient , a preoperative course of chemotherapy was requested to establish disease stability and non - appearance of other disease sites . in addition , all the patients were offered systemic therapy after the surgical removal of their metastatic disease . despite the fact that some patients did develop subsequent new sites of disease , all the patients remained radiologically disease free for significant periods of time after the pet probe guided intervention . because of the strict criteria of eligibility the number of patients offered the procedure is limited . an interesting application of pet probe guidance pertains to the diagnosis or restaging of lymphoma patients . directing the biopsy to the fdg active lesions this is especially true in areas that are difficult to access such as the mediastinum or retroperitoneum and after previous treatment when a repeat pet scan reveals an fdg avid spot in the background of large scarred down lymph nodes . the use of this technology for the removal of fdg avid metastatic breast cancer to axillary nodes especially in the re - operative setting and with difficult anatomy has been described by others . the role of high energy gamma probes for the resection of recurrent melanoma was described by frac et al . localization of metastatic lymph nodes in head and neck tumors , especially in re - operative and radiated fields , has become an area of special interest since the guidance provided by the pet probes can avoid damage to important nerves and vital organs in this area especially during difficult dissections . this particular topic was addressed by meller et al . comparing the accuracy of pet , ultrasound and pet probes localizing metastatic lymph nodes in head and neck malignancies . pet probes and ultrasound demonstrated a 95% sensitivity for both but the pet probe had a 60% specificity when compared with ultrasound with only 40% specificity . described the used of pet probes for detection of iodine in scans negative for recurrent thyroid tumors with 100% accuracy in 7 patients . studied the accuracy of high energy gamma probes in the detection of recurrent colon cancer . < 1 cm and with a mean standardized uptake value of 8.27 for true positive lesions and 3.65 for false negative lesions . this study included 21 patients with recurrent lesions in the rectum , peritoneum , abdominal wall , porta hepatis , retroperitoneum , pelvis , lung and liver . recent reports of the use of laparoscopic resection of occult metastasis in patients with ovarian cancer using a laparoscopic high energy gamma probe by barranger et al . this technique combines the accuracy of the pet probes with the advantages of minimally invasive surgery . the development of fdg imaging and its application in a growing number of malignancies has led to the clinical need for a high energy gamma probe . the applications for this device are rapidly expanding and new surgical possibilities are probably on the horizon .

abstractlocalizing positron emission tomography ( pet)/computed tomography ( ct ) findings in heavily scarred surgical fields can be challenging . a high energy gamma probe ( pet probe ) can be used to guide surgery in those difficult areas . we describe our experience localizing and removing fluorodeoxyglucose ( fdg ) avid lesions in different body areas . between 2004 and 2007 , we used the pet probe to localize and remove 12 lesions from 9 patients . the lesions were removed confirming ex vivo and tumor bed fdg activity . five patients had lesions in previously operated and sometimes radiated fields . one patient had fdg avid spots in the retroperitoneum . two lymphoma patients had been previously treated and had new fdg avid spots in a background of scarred nodes . the last patient had a core biopsy suspicious for lymphoma but a repeat ct was non - specific . one patient with gastric cancer patient , two patients with melanoma patients and two patients with breast cancer had 10 metastatic lesions easily identified and removed . after a median follow - up of 14 months all five patients are alive . the two patients with lymphoma had their fdg avid lymph nodes easily identified and biopsied . in one patient with melanoma and one patient with suspected lymphoma , the preoperative scan revealed no fdg avid lesions . the pet probe confirmed this finding in the operating room . clinical applications of pet probe guided surgery include restaging for previously treated lymphoma patients , localization and resection of metastatic fdg avid nodules especially in previously operated or radiated fields and biopsy of pet findings difficult to localize .

bone marrow mesenchymal stem cells were introduced into clinical practice due to their ability to differentiate into many types of cells . autologous matrix - induced chondrogenesis ( amic ) combines the microfracture method with matrix - based techniques that utilizes a collagen membrane to serve as a scaffold for new bone marrow mesenchymal stem cells , allowing effective reconstruction of even large fragments of a damaged cartilage surface . all - arthroscopic technique to repair knee cartilage defects using the amic technique , which includes the use of a collagen matrix ( porcine collagen type i and iii ) and fibrin glue technique presentation . this technical note introduces an all - arthroscopic amic technique to reconstruct extensive cartilage defects ( without bone defects ) . various techniques , both palliative and reparative , have been used to treat cartilage pathology with variable success rates [ 18 ] . bone marrow mesenchymal stem cells were introduced into clinical practice [ 3 , 5 , 7 ] due to their ability to differentiate into many types of cells [ 1 , 5 , 7 ] . in fact , bone marrow mesenchymal stem cells are considered to be an attractive source of cells for the regeneration of tissues and organs , including articular surface cartilage [ 1 , 3 , 5 , 7 ] . the simplest method for utilizing stem cells in the regeneration of a damaged cartilage layer is the microfracture technique [ 1 , 9 ] . autologous matrix - induced chondrogenesis ( amic ) combines the microfracture method with matrix - based techniques that utilizes a collagen membrane to serve as a scaffold for new cells , allowing effective reconstruction of even large fragments of a damaged cartilage surface [ 2 , 1013 ] . the goal of this article is to present an arthroscopic technique for reconstructing damaged knee cartilage fragments using the amic technique in conjunction with a collagen matrix ( porcine collagen type i and iii ( geistlich pharma ag , wolhusen , switzerland ) ) and fibrin glue ( tissucol , baxter , warsaw , poland ) . standard anterolateral and anteromedial arthroscopic approaches are utilized to evaluate the knee in general , as well as meniscal and cruciate ligament defects . after complete inspection of the joints and assessment of the defects , the chondral lesions are carefully debrided down to the subchondral bone with a curette , spoon , and shaver until a stable shoulder surrounded the defect . next , the size of each defect was assessed by a circular sharp punch of the appropriate diameter from an obi smith and nephew truffite reconstruction kit ( smith and nephew , andover , usa ) ( fig . 1 ) . this clearing creates a smooth , flat , circular defect surface with known dimensions and healthy cartilage edges . if the diameter of the cartilage defect does not exceed 11 mm , only one punch is used , and only one reconstruction area was prepared . if the defect is larger , more reconstruction areas are prepared using punches of appropriate sizes . corresponding numbers of circles are cut ( with the same knives ) in the chondro - gide collagen membrane ( geistlich pharma ag , wolhusen , switzerland ) after being moistened with physiological saline ( fig . joint and cartilage assessment and initial preparation of the cartilage defect area ( a ) . final preparation of the injured area with a punch from the smith and nephew obi reconstruction kit . an appropriately sized knife was introduced perpendicularly to the damaged surface ( b , c)fig . 2preparation of an appropriately sized chondro - gide membrane was performed by cutting circles in the moistened rectangular membrane using the knife previously used to prepare the cartilage defect area . thus , the obtained membrane circles perfectly matched the cartilage defect area in both shape and size ( a ) . chondro - gide membrane circles were introduced into the knee using surgical clamps ( b , c ) knee arthroscopy with fluid irrigation . joint and cartilage assessment and initial preparation of the cartilage defect area ( a ) . final preparation of the injured area with a punch from the smith and nephew obi reconstruction kit . an appropriately sized knife was introduced perpendicularly to the damaged surface ( b , c ) preparation of an appropriately sized chondro - gide membrane was performed by cutting circles in the moistened rectangular membrane using the knife previously used to prepare the cartilage defect area . thus , the obtained membrane circles perfectly matched the cartilage defect area in both shape and size ( a ) . chondro - gide membrane circles were introduced into the knee using surgical clamps ( b , c ) the second part of the procedure is performed under dry , arthroscopic conditions . according to recommendations specific to this method , numerous bores are drilled at 5-mm intervals in the subchondral layer with a 1.1-mm k - wire ( fig . 3 ) . next , chondro - gide membrane circles of corresponding diameters are placed in the reconstruction area with pean clamps . the circular patches overlap . according to the original technique , the porous surface of the membrane is facing the bone surface ( fig . 4 ) . fibrin glue ( tissucol , baxter , warsaw , poland ) is applied to all membrane - covered areas ( fig . next , excess glue is separated from the surrounding soft tissue , and the glue is left for 5 min to set . then , 10 knee movements ( consisting of flexion and extension ) are performed to check the stability of the reconstructed cartilage surface . if the membranes remained in place , the range of motion of the knee joint in which the reconstructed cartilage surface remained unloaded is recorded so as to determine the safe range of motion for subsequent rehabilitation . patients are provided with an adjustable - angle orthosis that stabilized the knee at a 15 angle for first 24 h after surgery.fig . according to the principles of amic , bores were drilled in the bone under dry , arthroscopic conditionsfig . membranes covered with a tissue glue layer ( b , c ) evacuation of fluid from the knee . according to the principles of amic , bores were drilled in the bone under dry , arthroscopic conditions the view of the chondro - gide membrane placed over the defect area . this technical note describes first arthroscopic method to perform the amic procedure to treat cartilage defects in the knee . technical progress has now made it possible to successfully apply arthroscopic techniques to reconstruct the damage of intra - articular knee structures ( such as menisci or cruciate ligaments ) . the evolution of operative technique in knee cartilage repair from open to arthroscopic surgery is known also in autologous chondrocyte implantation . described all - arthroscopic technique for aci - hyalograft c , which is very similar with the technique presented in this paper . the surgical technique for aci - hyalograft c has 2 stages : cartilage biopsy and graft implantation , which is the most important difference with all - arthroscopic amic technique . potential weakness of both all - arthroscopic aci - hyalograft c and amic technique versus open procedures is to use a few overlap circular patches of membrane fixed with glue . however , mobilization of the implanted patch has not been observed in marcacci and our series . in the original amic technique ( described by benthien ) , fibrin glue was used to secure the membrane in the defect area [ 2 , 10 , 11 ] . considering the fact that good results were reported following the use of fibrin glue , the use of sutures appears to be superfluous , when only the cartilage surface needs to be reconstructed [ 2 , 911 ] . stabilization of the chondro - gide membrane with glue requires a dry environment ; so to complete the amic procedure , the fluid has to be removed before gluing the membrane . some surgeons make use of special traction sets to generate these surgical spaces and placed patient in prone position . however , we found that with proper supine positioning , most cartilage defects on burdened knee joint surfaces are accessible for dry arthroscopy . here , we present all - arthroscopic technique to reconstruct extensive cartilage defects ( without bone defects ) . the procedure is a single - stage , all- arthroscopic technique based on the open amic procedure . clinical studies comparing this method with other methods or with active rehabilitation in randomized control trials is needed before the method can be recommended as a routine procedure .

purposebone marrow mesenchymal stem cells were introduced into clinical practice due to their ability to differentiate into many types of cells . autologous matrix - induced chondrogenesis ( amic ) combines the microfracture method with matrix - based techniques that utilizes a collagen membrane to serve as a scaffold for new bone marrow mesenchymal stem cells , allowing effective reconstruction of even large fragments of a damaged cartilage surface.methodsall-arthroscopic technique to repair knee cartilage defects using the amic technique , which includes the use of a collagen matrix ( porcine collagen type i and iii ) and fibrin glue technique presentation.conclusionthis technical note introduces an all - arthroscopic amic technique to reconstruct extensive cartilage defects ( without bone defects ) . the technique may be used for treatment of all location of knee cartilage lesions.level of evidencev .

M. Night Shyamalan has been a cinematic punching bag since at least “Signs” in 2002 — and even more so since “The Happening” in 2008. But with the far more successful “The Visit,” the director of 1999’s “The Sixth Sense” has finally made his scary return to form. The biggest frustration here is the found-footage style that’s attributed to a pair of likable teens. They want to document their first-ever trip to their grandparents’ farmhouse. The old folks, Nana (Deanna Dunagan) and Pop Pop (Peter McRobbie), aren’t on good terms with their daughter, known only as Mom (Kathryn Hahn). So Becca (Olivia DeJonge) aims to record everything in the hopes of her family achieving closure. But instead Becca mostly films her brother Tyler (Ed Oxenbould) goofing off, as well as Pop Pop’s constant wood-chopping. Oh, she also films Nana’s nightly habit of crawling around the house on all fours, stripping off her clothes and clawing at the walls. You know, just standard old-folks stuff. Obviously, something isn’t quite right with Nana and Pop Pop. And the whole thing straps the audience in for a wheelchair ride straight to crazy town. But it’s the fun kind of crazy. And “The Visit” is undeniably, admirably intense when it needs to be. Shyamalan’s previous feature was the big-budget Will and Jaden Smith bomb “After Earth” (2013). Now he’s written a messed-up fairy tale that often nails the sweet spot between scaring us and letting us laugh at how scared we are. It’s crowd-pleasing horror, the kind that can push moviegoers to the edge of their seats and send them to the water cooler the next day. This “Visit” is unlikely to leave a “Sixth Sense”-like dent on pop culture, and it may have a few too many easy scares. But the movie remains proof that Shyamalan can still keep you up at night. Who could have seen that twist coming? Sign up for BREAKING NEWS Emails privacy policy Thanks for subscribing! ||||| Well, here's an M. Night Shyamalan twist I don't think anybody saw coming, and I know nobody is going to mind. He made a good movie again. "The Visit" is a deceptively simple story about two adolescents meeting their grandparents for the first time. Mom's a little worried about sending the kids off alone – she's been estranged from her parents since she left home – but she thinks the teens will enjoy it. And they do, for a while. Until Nana starts wandering the house at night. Pop Pop spends an awful lot of time out in the shed doing... something. And – well, here's a hint, kids. If you ever feel like you're in a horror movie? And somebody warns you, Don't go in the basement? Please don't go in the basement. Despite plenty of familiar moments, "The Visit" still has surprises – including the traditional Shyamalan third-act fake-out. The real shock, though, is how brightly he's rekindled his talent. His last two, big-budget films – "After Earth" and "The Last Airbender" – were almost aggressively bad. And although many of his movies made money – that's how he could keep making them – who wants to see "The Village" again? (Hey, even Mark Wahlberg thought "The Happening" was a mistake, and Mark Wahlberg made "Ted 2.") Guessing, perhaps, that too much money and hype and Hollywood were the problems, Shyamalan decided to get basic – an under-the-radar shoot, one setting (except for a prologue and epilogue), no real special effects and only five actors (the biggest name of which is Kathryn Hahn, who appears briefly as the children's mother.) And all of it works. The children -- Olivia DeJonge and Ed Oxenbould – are legitimately gifted. And as the oddball elders, veteran character actors Deanna Dunagan – who is absolutely fearless – and Peter McRobbie keep the terror at a low, uncomfortable simmer. Until things finally, inevitably, boil over. But while the production values are simple, the script is sneakily complex. Like the best horror merchants, Shyamalan exploits our secret fears – in this case, of old age, ill health and dementia. And he both gives the children their own phobias – of mirrors, of inaction – and then provides them with a way to conquer them. There are some occasional lapses in logic. The film is yet another one of those herky-jerky found-footage conceits (although less annoying than most) and it ends with a moment of forced, familial uplift. And, I'm sorry, but the last thing I want my horror films to leave me with is a feel-good fadeout. But here's something to genuinely feel good about: This is M. Night Shyamalan's best movie since "Signs" – maybe since "The Sixth Sense." And the only scary twist to that would be if it makes him so cocky again he decides to do "Lady in the Water 2." Ratings note: The film contains violence, nudity and some gross-out horror. 'The Visit' (PG-13) Universal (94 min.) Directed by M. Night Shyamalan. With Olivia DeJonge, Ed Oxenbould, Deanna Dunagan, Peter McRobbie, Kathryn Hahn. Now playing in New Jersey. ★ ★ ★ ½ Stephen Whitty may be reached at [email protected]. Follow him on Twitter @stephenwhitty. Find him on Facebook.

– Two kids go on their first visit to Nana and Pop Pop's house to find out—and document via video cameras—what led to a family estrangement 15 years earlier in The Visit. They end up uncovering more than expected, including what goes bump in the night. Here's what critics are saying about M. Night Shyamalan's latest: "I smell a comeback," writes Brad Wheeler of Shyamalan, who has lately been accustomed to winning Razzies. The Visit is "a genuinely fun affair ... with the smirking air of a confidant and mischievous filmmaker," Wheeler writes at the Globe and Mail. Deanna Dunagan and Peter McRobbie as Nana and Pop Pop "are excellent at creepy," and that creepiness culminates in a solid twist, though he notes "the ultimate resolution has a bit of 'that’s it?' tidiness to it." "Despite plenty of familiar moments, The Visit still has surprises—including the traditional Shyamalan third-act fake-out," writes Stephen Whitty at the Star-Ledger. "The real shock, though, is how brightly he's rekindled his talent." Making a movie with five actors and no big special effects is risky, but "all of it works" as "Shyamalan exploits our secret fears ... of old age, ill health and dementia." Whitty says this is his "best movie since Signs—maybe since The Sixth Sense." Steven Rea at the Philadelphia Inquirer isn't quite so on board. This "isn't The Sixth Sense. It's not even Signs," he says. Sure, it "marks something of a return to form for Shyamalan" after big-budget duds The Last Airbender and Another Earth. But "isn't the whole handheld 'real-video' thing kind of old by now? Isn't the Shyamalanian-twist thing kind of old by now, too?" Peter Hall at the New York Daily News agrees "the biggest frustration here is the found-footage style." But this is "crowd-pleasing horror, the kind that can push moviegoers to the edge of their seats and send them to the water cooler the next day." The flick "often nails the sweet spot between scaring us and letting us laugh at how scared we are." Viewers, he says, get ready "for a wheelchair ride straight to crazy town."

lefschetz fibrations became a central tool in differential geometry and topology following donaldson s insight in the late 1990s @xcite that one can effectively explore the topological aspects of manifolds by studying smooth maps on them which have locally holomorphic character . since then they have gained a prominent role in symplectic topology , where a striking balance between flexibility and rigidity makes it possible to carry out topological constructions and geometric obstructions at the same time . in dimension @xmath0 , a firmer grasp on the quickly developing theory of lefschetz fibrations is pursued via factorizations in mapping class groups of surfaces @xcite . our goal is to better understand how surfaces in symplectic @xmath0manifolds arise in this setting . surfaces in @xmath0manifolds play a crucial role in our exploration of the topology of smooth and symplectic @xmath0manifolds ; they help determining the homeomorphism type , and distinguishing the diffeomorphism type . as observed by donaldson and smith @xcite , any symplectic surface can be seen as a _ multisection _ or an _ @xmath1section _ of a lefschetz fibration , which is a branched surface intersecting all the fibers positively @xmath1 times . in @xcite , we initiated an extensive study of symplectic surfaces via factorizations in more elaborate mapping class groups of surfaces . the current article aims to add to this effort by refining and exploring the correspondence between symplectic surfaces in symplectic @xmath0manifolds , multisections of lefschetz fibrations , and positive factorizations in surface mapping class groups . an isomorphism between two lefschetz fibrations @xmath2 with @xmath1sections @xmath3 , @xmath4 , is given by a pair of orientation - preserving diffeomorphisms between the total spaces @xmath5 and the base @xmath6spheres , which commute with @xmath7 and match @xmath3 . the mapping class group @xmath8 , which consists of orientation - preserving self - diffeomorphisms of the genus-@xmath9 surface @xmath10 preserving the set of marked points @xmath11 , is the host to the lift of any monodromy factorization of @xmath2 prescribed by an @xmath1section @xmath3 . there are simple modifications of monodromy factorizations that naturally arise from a few choices made in the process of extracting these factorizations from a given fibration which we describe and study in detail in the later sections . two monodromy factorizations in @xmath8 will be called hurwitz equivalent if one can be obtained from the other by applying a sequence of this finite set of simple modifications . our main theorem in this article is the following : [ mainthm ] for @xmath12 there exists a one - to - one correspondence @xmath13 when @xmath14 and @xmath15 , i.e. when the multisections are omitted , the above result is classical , due to kas @xcite and matsumoto @xcite . theorem [ mainthm ] is proved in section [ sec : equivalence ] , after a review of background results in section [ s : factorization multisection ] . we also provide an extension of this correspondence to one between _ framed _ multisections of lefschetz fibrations and monodromy factorizations in framed mapping class groups introduced in @xcite . in turn , through their monodromy factorizations , we obtain a full characterization of lefschetz _ pencils _ , up to isomorphisms that can permute base points ; see corollary [ t : equivalence pencils ] . in the last section , we turn to an intriguing question regarding the diversity of lefschetz fibrations versus that of pencils , which allows us to demonstrate how geometric , topological , and algebraic aspects of the theory of lefschetz fibrations can be nicely brought together . in @xcite , stipsicz asked whether every lefschetz fibration can be obtained as fiber sums of blown - up pencils ; that is to say , whether lefschetz pencils are the building blocks of all lefschetz fibrations via blow - ups and fiber sums . in section [ stipsicz ] , we will illustrate a way to produce counter - examples , using the well - known @xmath16chain relation in the mapping class group of a genus@xmath6 surface , along with monodromy modifications involving multisections , and a variety of geometric and topological results packaged in a recipe from @xcite we will be following here . we moreover show by appealing to above hurwitz equivalences that the only other counter - example we know of , a genus@xmath6 lefschetz fibration of auroux ( shown to be a counter - example by sato in @xcite ) , can also be derived from the same scheme . _ acknowledgements . _ the results of this article were partially presented by the second author at the 13th international workshop on real and complex singularities held in august 2014 at sao carlos , brazil . he would like to thank the organizers of the workshop for the opportunity and for their invitation to prepare this manuscript . the authors would also like to thank the anonymous referee for helpful comments . the first author was partially supported by the simons foundation grant @xmath17 . the second author was supported by jsps and capes under the japan - brazil research cooperative program and jsps kakenhi ( 26800027 ) . in this section we will briefly review the basic definitions and properties of lefschetz fibrations and their multisections , focusing on how they can be captured and studied as certain factorizations in mapping class groups of surfaces . for a more detailed exposition , the reader can turn to @xcite and @xcite . throughout the paper , all manifolds we work with are assumed to be closed , connected and oriented , unless otherwise noted . a _ lefschetz fibration _ @xmath18 is a smooth map @xmath19 , from a @xmath0manifold @xmath20 onto the @xmath6sphere , which only has _ nodal singularities _ , that is , for any @xmath21 in the _ critical locus _ @xmath22 , there exist orientation - preserving complex coordinate neighborhoods @xmath23 at @xmath24 and @xmath25 at @xmath26 , such that @xmath27 so @xmath28 is a submersion at all but finitely many points , where we have the local model of a complex nodal singularity . for @xmath9 the genus of a regular fiber , we call @xmath18 a _ genus@xmath9 lefschetz fibration_. a _ lefschetz pencil _ @xmath18 is a lefschetz fibration @xmath29 , where @xmath30 is a _ non - empty _ discrete set in @xmath20 , called the _ base locus _ , such that there exist an orientation - preserving complex coordinate neighborhood @xmath23 around each _ base point _ @xmath31 and a diffeomorphism @xmath32 , which together satisfy @xmath33.\ ] ] we say @xmath18 is a _ genus@xmath9 lefschetz pencil with @xmath1 base points _ for @xmath9 the genus of the regular fiber ( compactified by adding the base points ) , and @xmath34 . given a genus@xmath9 lefschetz pencil @xmath18 with @xmath1 base points , we can obtain a genus@xmath9 lefschetz _ fibration _ @xmath35 with @xmath1 disjoint sections @xmath36 of self - intersection @xmath37 , each arising as an exceptional sphere of the blow - up at the base point @xmath38 . the correspondence is canonical , as one can blow - down all the @xmath36 in the fibration @xmath39 to recover the pencil @xmath18 ( e.g. ( * ? ? ? * .8.1 ) ) . recall that a _ symplectic structure _ is a closed non - degenerate @xmath6form @xmath40 on a smooth manifold , such as the khler form on a complex algebraic variety . symplectic @xmath0manifold _ is then a pair @xmath41 . the prominent role of lefschetz fibrations in differential geometry and topology is mostly due to donaldson s amazing result from the late 1990s , who showed that an analogue of the classical lefschetz hyperplane theorem for complex algebraic surfaces holds in this more flexible setting : every _ symplectic _ @xmath0manifold admits a lefschetz pencil @xcite . conversely , generalizing an idea of thurston , gompf observed that every @xmath0manifold admitting a lefschetz pencil or a non - trivial ( i.e. with non - empty critical locus ) lefschetz fibration is symplectic @xcite . furthermore , one can strike a compatibility condition between the pairs @xmath41 and @xmath42 , which asks for the fibers of @xmath28 to be symplectic surfaces with respect to @xmath40 . every symplectic @xmath0manifold @xmath41 admits a compatible lefschetz pencil , and every lefschetz pencil / non - trivial fibration @xmath42 can be equipped with a compatible symplectic form . the main companion of a lefschetz fibration @xmath42 in this paper will be an embedded surface @xmath43 which sits in @xmath20 in a rather special way with respect to @xmath28 . [ @xcite][def : multisection ] a ( possibly disconnected ) closed oriented surface @xmath44 is called a _ multisection _ , or an _ @xmath1section _ , of a lefschetz fibration @xmath18 if it satisfies the conditions : 1 . the restriction @xmath45 is an @xmath1fold simple branched covering , 2 . the restriction of the differential @xmath46 preserves the orientation for any branched point @xmath47 of @xmath45 , where @xmath48 is a normal space of @xmath49 , which has the canonical orientation derived from that of @xmath20 , 3 . for any branched point @xmath50 of @xmath45 , there exist complex coordinate neighborhoods @xmath23 and @xmath25 which make the following diagram commute : @xmath51 a triple @xmath52 will denote a lefschetz fibration @xmath18 and its multisection @xmath43 . just like how a lefschetz fibration locally behaves like a holomorphic map , a multisection behaves like a holomorphic curve , intersecting the fibers all positively , and so that the restriction of the fibration map to it is a holomorphic branched covering onto @xmath53 . multisections are found in abundance , as observed by donaldson and smith ( who referred to them as _ standard surfaces _ ) : for any symplectic surface @xmath43 in a symplectic @xmath0manifold @xmath41 , there exists a compatible lefschetz pencil @xmath18 , such that @xmath43 is a multisection of @xmath54 , and conversely , for any triple @xmath55 , there exists a compatible symplectic form @xmath40 making the fibers and @xmath43 symplectic @xcite . we will make a few additional assumptions on @xmath56 , merely to simplify our upcoming discussions on how to describe lefschetz fibrations and their multisections in terms of certain factorizations in surface mapping class groups . first , we will assume that @xmath28 is injective on @xmath22 , and also that each branched point of a multisection , if not contained in @xmath22 , does not lie on a singular fiber , i.e. not contained in @xmath57 . both of these can be always achieved after a small perturbation . these assumptions will allow us to get standard local models for @xmath56 for the fibration over @xmath58 and not only _ around _ the isolated points in @xmath59 . it is also customary to assume that @xmath28 is _ relatively minimal _ , that is , no fiber contains a sphere with self - intersection @xmath37 , which otherwise could be blown - down without destroying the rest of the fibration . a lefschetz _ pencil @xmath18 is said to be _ relatively minimal _ , if no fiber component is a self - intersection @xmath60 sphere containing @xmath61 points of @xmath30 , to ensure that the associated lefschetz fibration @xmath39 is relatively minimal . as we will see shortly , this assumption is needed to guarantee that no information on the local topology is lost when we look at the monodromy of the fibration . for a surface @xmath62 and points @xmath63 , let @xmath64 be the group of orientation - preserving diffeomorphisms of @xmath62 which preserve the set @xmath11 . we call @xmath65 the _ mapping class group of @xmath62 with marked points @xmath66_. it consists of elements of @xmath64 , modulo isotopies fixing the set @xmath11 , where the group structure is induced by compositions of maps , that is , @xmath67\cdot [ \varphi_2 ] = [ \varphi_1\circ \varphi_2]$ ] for @xmath68 . let @xmath69 denote a genus@xmath9 surface with @xmath1 boundary components , and take points @xmath70 which cover the elements of @xmath71 . the _ framed mapping class group _ @xmath72 consists of orientation - preserving diffeomorphisms of @xmath69 which preserve set of marked points @xmath73 , modulo isotopies fixing the same data @xcite . clearly , one can pass to a closed surface @xmath74 by capping the boundaries by disks , the centers of which we label as @xmath75 . this boundary capping map induces a surjective homomorphism @xmath76 now let @xmath18 be a lefschetz fibration with @xmath77 critical points , @xmath43 its @xmath1section and @xmath78 the set of branched points of @xmath45 away from @xmath22 . set @xmath79 , and take paths @xmath80 with a common initial point @xmath81 such that * @xmath82 are mutually disjoint except at @xmath83 , * @xmath84 connects @xmath83 with @xmath85 , * @xmath82 are ordered counterclockwise around @xmath83 , i.e. there exists a small loop around @xmath83 oriented counterclockwise , hitting each @xmath84 only once in the given order . we take a loop @xmath86 with the base point @xmath83 by connecting @xmath84 with a small counterclockwise circle with center @xmath85 . let @xmath87 be a horizontal distribution of @xmath88 , that is , @xmath89 is a plane field such that @xmath90 for any @xmath91 . we assume that @xmath92 for any @xmath93 . using @xmath87 , we can take a lift of the direction vector field of @xmath86 and a flow of this lift gives rise to a self - diffeomorphism of @xmath94 . we call this diffeomorphism a _ parallel transport _ of @xmath86 and its isotopy class a _ local monodromy _ around @xmath85 . note that a local monodromy does not depend on the choice of @xmath87 . indeed , for any horizontal distribution @xmath87 we can find a riemannian metric @xmath9 such that @xmath95 is equal to @xmath96 , in particular for any two horizontal distribution there exists a one - parameter family of horizontal distributions connecting the given two distributions . under an identification of the pair @xmath97 with @xmath98 , we can regard a parallel transport as a diffeomorphism in @xmath99 , and thus , a local monodromy as a mapping class in @xmath8 . we denote this mapping class by @xmath100 . since the concatenation @xmath101 is null - homotopic in @xmath102 , the composition @xmath103 is the unit element of the group @xmath8 . the factorization @xmath104 is called a _ monodromy factorization of the triple @xmath56 _ , which we will denote in short by @xmath105 ( as a _ word _ in @xmath106 ) . analyzing the local models around @xmath22 and @xmath107 ( which , remember , might contain in common the type ( 3 ) branched points in definition [ def : multisection ] ) , we identify three standard elements in the mapping class group @xmath8 that appear as a factor @xmath100 above @xcite : if the fiber @xmath108 contains a lefschetz critical point which is not a branched point of @xmath45 , then @xmath100 is a right - handed dehn twist along some simple closed curve @xmath109 , which is called a _ vanishing cycle _ of a lefschetz critical point in @xmath108 @xcite . ( relative minimality of @xmath18 now guarantees that @xmath110 is not null - homotopic , so we do not have a `` hidden '' dehn twist factor . ) if @xmath108 contains a branched point of @xmath43 away from @xmath22 , then @xmath100 is a half twist @xmath111 along some path @xmath112 between some @xmath113 and @xmath114 . lastly , if @xmath85 is the image of a point in @xmath115 , we get a mapping class @xmath100 which is represented by a dehn twist @xmath116 shown in figure [ f : lift dehntwist ] for some simple closed curve @xmath117 going through @xmath113 and @xmath114 . observe that under the forgetful homomorphism , only @xmath100 that are dehn twists ( possibly going through @xmath107 ) survive , yielding the standard monodromy factorization @xmath118 of @xmath18 of the form @xmath119 in @xmath120 . in other words , the factorization @xmath105 is a _ lift _ of the factorization @xmath118 . it is worth noting that each standard element @xmath100 discussed above , let it be a dehn twist or an arc twist , comes with a preferred orientation , corresponding to positive ( right - handed ) dehn twists and arc / braid twists . any factorization @xmath121 in @xmath8 , which consists of only these three types of elements is called a _ positive factorization _ ( of the identity ) in @xmath8 , and it conversely gives rise to a triple @xmath56 . we can summarize these as follows ( which is a direct corollary of ( * ? ? ? * theorem 1.1 ) obtained by applying the boundary capping homomorphism to the framed mapping class group ) : @xcite [ mainquote ] let @xmath52 be a genus@xmath9 lefschetz fibration with @xmath77 critical points , where @xmath43 is a connected @xmath1section which has @xmath61 branched points away from @xmath22 and @xmath122 branched points on @xmath22 . then @xmath56 has a monodromy factorization @xmath105 of the form @xmath121 in @xmath8 , where among @xmath100 @xmath61 many are half - twists @xmath123 , @xmath122 many are dehn twists @xmath124 through two marked points in @xmath11 , and the rest are dehn twists along curves missing the marked points . moreover , @xmath125 and the union @xmath126 is connected , where @xmath127 is the union of paths between points in @xmath11 corresponding half twists in the factorization and @xmath128 is the union of simple closed curves going through two points in @xmath11 corresponding lifts of dehn twists in the factorization . conversely , from any such positive factorization of @xmath129 in @xmath8 , subject to conditions listed above , one can construct a genus@xmath9 lefschetz fibration @xmath18 with @xmath77 vanishing cycles @xmath130 , and a connected @xmath1section @xmath43 of genus @xmath131 . we can modify theorem [ mainquote ] so that it also holds for a _ disconnected _ multisection : in this case the union @xmath126 is not necessarily connected ( the number of components of the union coincides with that of @xmath43 ) , and the euler characteristic @xmath132 is equal to @xmath133 . [ r : lift factorization ] as we have shown in @xcite the positive factorization @xmath105 of the identity element in @xmath8 lifts to another positive factorization of a product of boundary parallel dehn twists in @xmath72 . this geometrically corresponds to removing a framed tubular neighborhood of @xmath43 . the latter positive factorization consists of standard factors @xmath134 , which are dehn twists in the interior of @xmath69 , and the lifts of @xmath111 and @xmath135 as shown in figure [ f : lift localmonodromy ] , both of which interchange the two boundary components in prescribed ways . and @xmath135 . , height=90 ] for simplicity , we denote these lifts by @xmath111 and @xmath135 as well . this monodromy factorization in the framed mapping class group allows us to capture the self - intersection number of @xmath43 . the goal of this section is to establish a one - to - one correspondence between triples @xmath56 , where @xmath43 is an @xmath1section of a genus@xmath9 lefschetz fibration @xmath18 , and positive factorizations @xmath136 of the form @xmath121 in @xmath8 , modulo natural equivalence relations on both sides , which we will spell out right away . the triples @xmath137 , @xmath4 , are said to be _ equivalent _ ( or _ isomorphic _ ) if there exist orientation - preserving diffeomorphisms @xmath138 and @xmath139 such that @xmath140 and @xmath141 . clearly , a necessary condition for @xmath142 to be equivalent is that both fibrations @xmath7 should have the same genus @xmath9 , and the multisections @xmath3 should have the same covering degree @xmath1 . as we noted in the previous section , a monodromy factorization @xmath143 does not depend on the choice of a horizontal distribution @xmath87 . it does however depend on the choice of paths @xmath82 and that of an identification of @xmath97 with @xmath98 . identical to the well - known case of a monodromy factorization of a _ pair _ @xmath18 one can ( see e.g. @xcite ) easily verify that two monodromy factorizations for a triple @xmath56 , derived from different choices of paths and identifications can be related by successive applications of the following two types of modifications : 1 . _ elementary transformation _ , which changes a factorization as follows : @xmath144 + note that @xmath145 in the right hand side represents a single factor of the factorization . 2 . _ global conjugation _ , which changes each member of a factorization by the conjugation of some mapping class @xmath146 : @xmath147 we will thus call two factorizations of the unit element @xmath148 _ hurwitz equivalent _ if one can be obtained from the other after a sequence of these two types of modifications . this subsection will be devoted to the proof of the following theorem , which , together with theorem [ mainquote ] , implies the main result of our paper , theorem [ mainthm ] . [ t : equivalence multisection factorization ] let @xmath142 , @xmath4 be a genus@xmath9 lefschetz fibration with an @xmath1section @xmath3 . suppose that @xmath149 is negative , that is , @xmath150 is a hyperbolic surface for a regular value @xmath83 . the triples @xmath151 and @xmath152 are equivalent if and only if their monodromy factorizations @xmath153 and @xmath154 are hurwitz equivalent . to prove theorem [ t : equivalence multisection factorization ] , we will need a few preliminary results on mapping classes in @xmath8 . [ t : isotopy equality half twist ] let @xmath155 be simple paths between distinct marked points @xmath156 and @xmath113 . then @xmath157 in @xmath8 if and only if @xmath158 and @xmath159 are isotopic relative to the points @xmath160 . the `` if '' part is obvious . to prove the `` only if '' part we assume that @xmath158 and @xmath159 are not isotopic and show that @xmath161 and @xmath162 are not equal . for simple curves @xmath163 , we denote the geometric intersection number of @xmath164 and @xmath165 by @xmath166 , that is , @xmath166 is the minimum number of intersections between two curves isotopic ( relative to @xmath160 ) to @xmath164 and @xmath165 . without loss of generality we may assume that @xmath158 and @xmath159 are in minimal position . let @xmath167 be the boundary of a regular neighborhood of @xmath158 . the curve @xmath167 does not intersect @xmath158 . on the other hand , @xmath168 is not equal to @xmath169 . to see this , we will check that there is no bigon between sub - paths of @xmath167 and @xmath159 ( see the bigon criterion in @xcite ) . as shown in figure [ f : simple closed curve d ] there are three types of regions which are candidates of such bigons . the two shaded regions in figure [ f : simple closed curve d1 ] can not be bigons since @xmath158 and @xmath159 are in minimal position . since @xmath158 and @xmath159 are not isotopic , the shaded region in figure [ f : simple closed curve d2 ] is not a bigon . since @xmath170 is equal to @xmath169 , it is sufficient to prove that @xmath171 is not equal to @xmath169 . let @xmath172 be the simple closed curve obtained by changing a parallel copy of @xmath167 around @xmath159 as shown in figure [ f : result halftwist ] . the curve @xmath172 represents the isotopy class @xmath173 . and @xmath172 around @xmath159 . , height=94 ] it is easy to see that the number of the intersections between @xmath167 and @xmath172 is equal to @xmath174 . in what follows , we will prove that @xmath167 and @xmath172 are in minimal position using the bigon criterion . as shown in figure [ f : candidate bigon ] there are six types of regions which are candidates of innermost bigons . if the far right region in figure [ f : candidate bigon1 ] were a bigon , @xmath167 would be isotopic to a small circle with center @xmath113 , but it is not the case since @xmath167 does not intersect @xmath158 . similarly , we can also verify that the far left region in figure [ f : candidate bigon2 ] is not a bigon . if either of the rest of two regions in figure [ f : candidate bigon1 ] were a bigon , then @xmath167 and @xmath159 would form a bigon , which contradicts the assumption that @xmath167 and @xmath159 are in minimal position . as for the rest of two regions in figure [ f : candidate bigon2 ] , either the boundary of them contain at least two sub - paths of @xmath167 , or they contain the point @xmath156 or @xmath113 . in either case , these regions can not be bigons . we can eventually conclude that @xmath172 and @xmath167 are in minimal position , and thus , @xmath175 . [ t : non commutable classes ] let @xmath117 be a simple closed curve going through @xmath156 and @xmath113 which is not null - homotopic ( as a curve in @xmath10 ) , and @xmath112 the closure of a component of @xmath176 . for any @xmath177 the mapping classes @xmath135 and @xmath178 do not commute , that is , @xmath179 \neq 1 $ ] in @xmath8 . since @xmath135 commutes with @xmath178 if and only if @xmath180 commutes with @xmath181 , we may assume @xmath182 without loss of generality . let @xmath183 be the closure of the complement @xmath184 and @xmath167 and @xmath172 the boundaries of regular neighborhoods of @xmath185 and @xmath183 , respectively . the curve @xmath186 is isotopic to @xmath172 , while @xmath187 is isotopic to @xmath188 . we will prove that @xmath172 and @xmath188 are not isotopic by showing @xmath189 . the curve @xmath188 is described in figure [ f : half twisted curve ] . . the central bold curve is @xmath185 . , height=94 ] it intersects with @xmath110 at @xmath190 points . we easily see that none of the regions made by @xmath188 and @xmath110 in figure [ f : half twisted curve ] , except for the shaded ones , can be bigons . furthermore , neither of the shaded regions can be a bigon since @xmath110 is not null - homotopic in @xmath10 . thus the curve @xmath188 is in minimal position with @xmath110 , and @xmath191 for @xmath192 , as claimed . [ t : isotopy equality lift dehn twist ] let @xmath193 be simple closed curves going through @xmath156 and @xmath113 which are not null - homotopic ( as curves in @xmath10 ) . then @xmath194 in @xmath8 if and only if @xmath195 and @xmath196 are isotopic relative to the points @xmath160 . once again the `` if '' part of the statement is obvious . assume that @xmath195 and @xmath196 are not isotopic . we will prove that @xmath197 and @xmath198 are not equal . by an isotopy relative to the points @xmath160 , we change @xmath195 and @xmath196 so that these are in minimal position . we first note that , if we can find a simple closed curve @xmath199 away from @xmath195 such that @xmath200 is not equal to @xmath169 , we can prove that @xmath197 and @xmath198 are different mapping classes in the same way as in the proof of ( * ? ? * fact 3.6 ) . * case 1 * : suppose that both of the components of @xmath201 intersect @xmath196 . we may assume that , at each of the points @xmath156 and @xmath113 , either @xmath195 and @xmath196 intersect transversely or these are tangent to each other . let @xmath202 be a tubular neighborhood of @xmath195 and @xmath203 small neighborhoods of @xmath204 . if @xmath195 and @xmath196 are tangent to each other at both of the points , then one of the following holds : * the intersections @xmath205 and @xmath206 are contained in the same component of @xmath207 ( see figure [ f : bigon pair path3 ] ) , * the component of @xmath207 containing @xmath205 is different from that containing @xmath206 ( see figure [ f : bigon pair path additional 1 ] ) . altogether we have to consider the four cases described in figures [ f : bigon pair path1 ] [ f : bigon pair path additional 1 ] . for each case we take a parallel copy @xmath208 of @xmath195 as shown in the figures . we can easily verify that no region made by @xmath208 and @xmath196 in figures [ f : bigon pair path1 ] , [ f : bigon pair path2 ] and [ f : bigon pair path3 ] can be a bigon . ( recall that @xmath195 and @xmath196 are assumed to be in minimal position . ) in these cases , we put @xmath209 , which satisfies the desired conditions ( i.e. away from @xmath195 and @xmath210 ) . in particular we can deduce that @xmath197 and @xmath198 are different mapping classes . as for the last case , the shaded region in figure [ f : bigon pair path additional 1 ] can be a bigon . if this region is a bigon , we move @xmath208 to @xmath211 so that it avoids all the bigons nested around @xmath113 ( see figure [ f : bigon pair path additional 2 ] ) . it is easy to see that @xmath212 is not empty and no region made by @xmath211 and @xmath196 in figure [ f : bigon pair path additional 2 ] can be a bigon . thus @xmath213 satisfies the desired conditions . * case 2 * : suppose that one of the components of @xmath201 intersects @xmath196 but the other one does not . as in case 1 , we have to consider four cases according to the configuration of @xmath196 around @xmath156 and @xmath113 . in each case we take parallel copies of @xmath195 as shown in figures [ f : bigon pair paths case 2 ] , [ f : bigon pair paths case 2_2 ] and [ f : bigon pair paths case 2_3 ] . it is easy to verify that either of the shaded regions in figure [ f : bigon pair path8 ] is not a bigon . thus , either of the parallel curves of @xmath195 in the figure is in minimal position with @xmath196 . if the shaded region in figure [ f : bigon pair path10 ] is not a bigon , then the parallel curve in the figure is in minimal position with @xmath196 . we can move @xmath196 by an isotopy so that it intersects @xmath195 transversely on both @xmath156 and @xmath113 if the shaded region in figure [ f : bigon pair path10 ] is a bigon . in this case , we can take a curve @xmath214 so that it is away from @xmath195 and @xmath210 . none of the regions made by @xmath196 and the parallel copy of @xmath195 in figure [ f : bigon pair path9 ] , except for the shaded one , can be bigons . if the shaded region in figure [ f : bigon pair path9 ] is not a bigon , then the parallel copy of @xmath195 in the figure is in minimal position with @xmath196 . if the shaded region in figure [ f : bigon pair path9 ] is a bigon , we move the parallel copy of @xmath195 so that it avoids all the bigons nested around the shaded region ( see figure [ f : bigon pair path9_2 ] ) . it is easily verified ( using bigon criterion ) that the resulting curve @xmath167 is in minimal position with @xmath196 . if @xmath167 has non - empty intersection with @xmath196 , we can deduce that @xmath197 and @xmath198 are different mapping classes . if @xmath167 is away from @xmath196 , we take another parallel copy of @xmath195 `` inside '' @xmath195 as shown in figure [ f : bigon pair path9_2 ] . this copy is in minimal position provided that the shaded region in figure [ f : bigon pair path9_2 ] is not a bigon . if it is a bigon , we again move the copy so that it avoids all the bigons nested around the shaded region . it is easily verify that the resulting curve @xmath172 is in minimal position with @xmath196 . we can deduce @xmath215 provided that @xmath172 intersects with @xmath196 . if @xmath172 is away from @xmath196 , then @xmath196 is as shown in figure [ f : bigon pair path9_3 ] , in particular it is isotopic to @xmath216 for some @xmath217 , where @xmath185 is a path between @xmath156 and @xmath113 in figure [ f : bigon pair path9_3 ] . we can thus deduce from lemma [ t : non commutable classes ] that @xmath197 and @xmath218 are different mapping classes . none of the regions made by @xmath196 and the parallel copy of @xmath195 in figure [ f : bigon pair path11 ] , except for the shaded one , can be bigons . thus we can deduce @xmath215 provided that the shaded region in figure [ f : bigon pair path11 ] is not a bigon . if the shaded region is a bigon , we move the parallel copy by an isotopy so that it avoids all the bigons nested around the shaded one in figure [ f : bigon pair path11 ] ( see figure [ f : bigon pair path11_2 ] ) . it is easily verified that the resulting curve @xmath219 is in minimal position with @xmath196 , so we can deduce @xmath215 provided that @xmath219 intersects with @xmath196 . if @xmath219 is away from @xmath196 , we take another parallel copy of @xmath195 `` inside '' @xmath195 as shown in figure [ f : bigon pair path11_2 ] . this copy is in minimal position provided that the shaded region in figure [ f : bigon pair path11_2 ] is not a bigon . if it is a bigon , we again move the copy so that it avoids all the bigons nested around the shaded region . it is easy to check that the resulting curve @xmath220 is in minimal position with @xmath196 . the curve @xmath220 must intersect with @xmath196 . for , if @xmath220 were away from @xmath196 , @xmath220 is as shown in figure [ f : bigon pair path9_3 ] , in particular it would be disconnected if the number @xmath221 of strands of paths is odd , or null - homotopic ( as a curve in @xmath10 ) if @xmath221 is even , but both of the consequences contradict our initial assumptions . we conclude that @xmath197 and @xmath198 are different mapping classes . * case 3 * : suppose that neither of the components of @xmath201 intersect @xmath196 . as before , we consider four cases according to the configuration of @xmath196 around @xmath156 and @xmath113 . in each case we take parallel copies of @xmath195 as shown in figure [ f : bigon pair paths case 3 ] . if both of the parallel copies of @xmath195 in figure [ f : bigon pair path4 ] formed bigons with @xmath196 , either @xmath196 would be homotopic to @xmath195 or @xmath196 is null - homotopic ( as a simple closed curve in @xmath10 ) , which contradicts the assumptions . thus either one of the copies in figure [ f : bigon pair path4 ] is in minimal position with @xmath196 , and we can deduce @xmath215 . the parallel copy of @xmath195 in figure [ f : bigon pair path5 ] is in minimal position with @xmath196 since these intersect at a single point . if both of the shaded regions in figure [ f : bigon pair path6 ] are not bigons , @xmath196 and the copy in the figure are in minimal position . if either of the shaded regions in figure [ f : bigon pair path6 ] is a bigon , we can move @xmath195 by a isotopy so that @xmath195 and @xmath196 intersect transversely at @xmath156 and @xmath113 . in both cases , we can deduce @xmath215 . if the shaded region in figure [ f : bigon pair path7 ] were a bigon , @xmath196 would be homotopic to @xmath195 , which contradicts the assumptions . thus , @xmath196 and the copy in figure [ f : bigon pair path7 ] are in minimal position . we should point out that one can not state lemmas [ t : isotopy equality half twist ] and [ t : isotopy equality lift dehn twist ] for the lifts of the elements featured in them to the framed mapping class group @xmath72 instead . for example , for the paths @xmath185 and @xmath222 between @xmath156 and @xmath113 , which are not isotopic ( relative to the boundary of @xmath69 ) in general , we can see that @xmath111 is equal to @xmath223 in @xmath72 . there are in fact infinitely many such lifts of arc twists in @xmath8 , which is the underlying cause for this ambiguity . next is a variation of a classical result of earle and schatz @xcite : [ t : contractibility diff ] if @xmath149 is negative , then @xmath224 is trivial . as in the proof of ( * theorem 4.6 ) , we can obtain the following exact sequence ( note that we omit the base points for simplicity ) : @xmath225 where @xmath226 is the configuration space defined in @xcite , which is aspherical if @xmath227 . since the group @xmath228 is trivial for @xmath14 ( @xcite ) , so is @xmath229 if @xmath14 . furthermore , the following diagram commutes : @xmath230_{\cong } \\ \pi_1(\diff(t^2 ) ) \ar[r]^{\mathrm{ev}_\ast } & \pi_1(f_{0,n}(t^2 ) ) \ar[u]_{\pi_\ast } , } \ ] ] where @xmath231 is induced by the natural projection and @xmath232 is induced by the evaluation map , which is the same map as that in . in particular , @xmath232 is injective . we can thus deduce from the exact sequence that @xmath233 is trivial for @xmath234 . we can also obtain the following exact sequence : @xmath235 the configuration space @xmath236 is aspherical for @xmath237 ( @xcite ) . thus , if the fundamental group @xmath238 is trivial , so is @xmath229 . using we can verify that @xmath239 is an infinite cyclic group generated by the loop @xmath240 , where @xmath241 is the @xmath242degree rotation of @xmath243 fixing @xmath244 . since @xmath245 , especially @xmath246 , @xmath247 is also an infinite cyclic group generated by @xmath248 . it is easy to see that @xmath249\in \pi_1(\diff(\sigma_g;\{s_1,s_2\}))$ ] is sent to the generator of @xmath250 . we can eventually conclude that @xmath229 is trivial for any @xmath251 . the above lemma can be possibly derived as a corollary of the contractibility of the identity component of @xmath252 , as shown in @xcite , provided @xmath252 is seen to be homotopy equivalent to @xmath99 . for our purposes however , it is sufficient to calculate the fundamental group of @xmath99 . so we have given a direct proof of lemma [ t : contractibility diff ] . we are now ready to prove the theorem . we first assume that @xmath151 and @xmath152 are equivalent . we can take diffeomorphisms @xmath138 and @xmath139 such that @xmath253 and @xmath254 . let @xmath255 be reference paths for @xmath256 with the common initial point @xmath83 which give rise to the factorization @xmath153 under an identification @xmath257 . let @xmath258 , @xmath259 and @xmath260 , which is an identification of @xmath261 with @xmath262 . it is easily verify that the monodromy factorization of @xmath263 obtained from @xmath264 and @xmath265 coincides with @xmath153 . since any two factorizations of @xmath152 are hurwitz equivalent , so are @xmath153 and @xmath154 . in what follows we assume that @xmath153 and @xmath154 are hurwitz equivalent . we first consider the case that @xmath7 has no critical points and @xmath266 has no branched points . in this case , @xmath7 can be obtained by pasting two trivial surface bundles over the disk so that the marked points corresponding @xmath1sections match . by lemma [ t : contractibility diff ] such a pasting map is unique up to isotopy preserving fibration structures . thus @xmath256 and @xmath263 are equivalent . assume that @xmath7 has critical points or @xmath266 has branched points . we can take reference paths @xmath267 for @xmath7 so that the local monodromies associated with @xmath268 and @xmath269 coincide . by composing a self - diffeomorphism of @xmath243 to @xmath263 , we may assume that @xmath270 and @xmath271 coincide . let @xmath272 and @xmath273 a sufficiently small disk neighborhood of @xmath274 . since all the local monodromies of @xmath256 and @xmath263 coincide , we can take a diffeomorphism @xmath275 sending the intersection @xmath276 to @xmath277 such that the following diagram commutes : @xmath278^{h } \ar[d]^{f_1 } & f_2^{-1}(s^2\setminus \amalg_jd_j ) \ar[dl]^{f_2 } \\ s^2\setminus \amalg_jd_j . } \ ] ] in what follows we will extend @xmath279 to a diffeomorphism with the source containing the preimages @xmath280 . if @xmath281 contains a lefschetz critical point which is not a branched point of @xmath266 , then in the same manner as in the proof of ( * ? ? ? * theorem 2.4 ) we can extend @xmath279 to a diffeomorphism with the source containing @xmath282 ( in this procedure we need lemma [ t : contractibility diff ] instead of the contractibility of @xmath283 used in @xcite ) . assume that @xmath281 contains a lefschetz critical point @xmath284 which is also a branched point of @xmath266 . there exist complex coordinate neighborhoods @xmath285 and @xmath286 at @xmath287 and @xmath288 , respectively , which satisfy the following properties : 1 . @xmath289 , 2 . @xmath290 . using the disk theorem as in the proof of ( * ? ? ? * theorem 2.4 ) , we may assume that @xmath291 and @xmath292 coincide without loss of generality . by lemma [ t : isotopy equality lift dehn twist ] the vanishing cycles associated with @xmath268 and @xmath269 coincide up to isotopy relative to the points @xmath160 . thus , in the same way as that in the proof of ( * ? ? ? * lemma 2.5 ) , we can change @xmath279 by a vertical isotopy ( in the sense of @xcite ) sending @xmath293 to @xmath294 at all times so that @xmath295 on a neighborhood ( in @xmath296 ) of the vanishing cycle of @xmath256 associated with @xmath268 . the arguments following the proof of ( * ? ? ? * lemma 2.5 ) can be applied to our situation , and we can eventually extend @xmath279 to a diffeomorphism with the source containing @xmath282 . lastly , if @xmath281 contains a branched point of @xmath266 away from @xmath297 , then we can extend @xmath279 to a diffeomorphism with the source containing @xmath282 in a manner quite similar to that in the previous paragraph , where we invoke lemma [ t : isotopy equality half twist ] instead of lemma [ t : isotopy equality lift dehn twist ] this time . as discussed in the previous section ( cf . remark [ r : lift factorization ] ) we can take a lift of the factorization @xmath105 to that of a product of dehn twists along boundary components in the framed mapping class group @xmath72 . such a lift is needed to fully capture the local topology of the multisection @xmath43 . two such lifts @xmath298 of @xmath299 , for @xmath4 , are not necessarily related by elementary transformations and simultaneous conjugations even if @xmath151 and @xmath152 are equivalent . there is indeed no canonical way to choose lifts of @xmath111 and @xmath135 . for instance , each one of the paths @xmath300 , @xmath4 in figure [ f : lifts path ] is a lift of @xmath185 , and in turn , @xmath301 is a lift of @xmath302 . and @xmath113.,width=264 ] it is easy to see that @xmath162 is equal to @xmath303 , where @xmath304 is a simple closed curve along the boundary component containing @xmath305 . thus , different choices of lifts of @xmath111 and @xmath135 in @xmath299 might yield a factorization @xmath298 with distinct products , in particular the hurwitz equivalence class of @xmath298 depends on the choices of lifts of members in @xmath299 . for lifts of @xmath111 and @xmath135 are uniquely determined up to conjugations by dehn twists along boundary components however , @xmath298 is uniquely determined up to elementary transformations , simultaneous conjugations , plus a third modification : 1 . _ framing conjugation _ , which changes a factorization as follows : @xmath306 where @xmath307 is a simple closed curve along a boundary component of @xmath69 . a framing conjugation does not affect usual dehn twists among the @xmath100 factors since any simple closed curve can be isotoped away from the boundary ( but does affect lifts of dehn twists ) . in particular , this move is not needed to relate monodromy factorizations in @xmath72 associated to _ pure multisections _ , i.e. disjoint union of sections . we say that two positive factorizations of products of dehn twists along boundary components in @xmath72 are _ hurwitz equivalent _ , if one can be obtained from the other by a sequence of elementary transformations , simultaneous conjugations and framing conjugations . for @xmath4 , let @xmath137 be a genus@xmath9 lefschetz fibration with an @xmath1section @xmath3 , with monodromy factorization @xmath308 in @xmath8 . let @xmath298 be a lift of @xmath308 , a positive factorization of the form @xmath309 in @xmath310 . then theorem [ t : equivalence multisection factorization ] , together with the above observation , thus yields to a one - to - one correspondence in this setting as well : [ t : equivalence multisection factorization framed ] suppose that @xmath149 is negative . the triples @xmath151 and @xmath152 are equivalent if and only if @xmath311 and @xmath312 are hurwitz equivalent . it is worth noting that a framing conjugation can also affect the right hand side of a positive factorization @xmath313 in the framed mapping class group , simultaneously increasing and decreasing the powers of the involved boundary twists . in order to make the effect of a framing conjugation clear , let us define the following surjective homomorphism @xmath314 defined by the action of a mapping class on the set @xmath73 , where @xmath315 is the symmetric group of order @xmath1 . a dehn twist @xmath316 is contained in the kernel of @xmath317 , while a half twist @xmath111 and a lift @xmath135 of a dehn twist are sent to transpositions by @xmath317 . clearly @xmath318 is equal to @xmath319 for any @xmath320 , so a framing conjugation changes the right hand side of the factorization as follows : @xmath321 given a genus@xmath9 lefschetz pencil @xmath18 with base locus @xmath322 , recall that we can pass to a genus@xmath9 lefschetz _ fibration _ @xmath39 , with a distinguished _ pure _ @xmath1section @xmath43 that consists of @xmath1 disjoint sections @xmath36 of self - intersection @xmath37 , each arising as an exceptional sphere in @xmath323 of the blow - up at the base point @xmath324 . since one can blow - down all @xmath36 to recover the pencil @xmath18 , we can work with the well - known monodromy factorization @xmath325 of @xmath326 of the form @xmath327 in the framed mapping class group @xmath72 . note that this factorization is in fact contained in the subgroup @xmath328 ( whose elements restrict to identity along @xmath329 ) which only captures _ pure _ @xmath1sections , but we need the larger group in order to factor in pencil automorphisms which swap base points , which we will discuss shortly . this associated factorization is what we will call monodromy factorization of the _ pencil _ @xmath18 , and with the above correspondence in mind , we will denote it simply by @xmath118 . lefschetz pencils @xmath330 , @xmath4 , are said to be _ equivalent _ if there exist orientation - preserving diffeomorphism @xmath138 and @xmath139 such that @xmath331 and @xmath332 . clearly , for @xmath2 to be equivalent pencils , they should both have the same fiber genus and the same number of base points @xmath333 . it now follows from theorem [ t : equivalence multisection factorization ] that : [ t : equivalence pencils ] two lefschetz pencils @xmath2 of genus @xmath334 with @xmath1 base points are equivalent if and only they have hurwitz equivalent monodromy factorizations @xmath335 in @xmath72 . since @xmath336 and @xmath337 , we have @xmath338 . if @xmath256 and @xmath263 are equivalent , then the corresponding pairs of lefschetz fibrations and these sections are also equivalent . thus , @xmath339 and @xmath340 are hurwitz equivalent by corollary [ t : equivalence multisection factorization framed ] . suppose that @xmath339 and @xmath340 are hurwitz equivalent . let @xmath341 be the associated lefschetz fibration . we deduce from theorem [ t : equivalence multisection factorization ] , and the assumption that there exist diffeomorphisms @xmath342 and @xmath139 such that @xmath343 sends the union of exceptional spheres of @xmath344 to that of @xmath345 and @xmath346 . so @xmath343 induces a diffeomorphism @xmath138 which satisfies @xmath347 and @xmath253 , providing an equivalence between @xmath348 and @xmath349 . the hurwitz equivalence in the statement of corollary [ t : equivalence pencils ] is not the classical one for fibrations , it is our ( extended ) hurwitz equivalence for monodromy factorizations in the framed mapping class group , allowing the exceptional sections / base points to be interchanged . although we believe the above corollary to be known to experts , we are not aware of any proof of it in the literature . although every lefschetz pencil gives rise to a lefschetz fibration on a blow - up of its total space , the converse is known to be false . as shown by stipsicz @xcite , and independently by smith @xcite , if @xmath18 is a fiber sum of two nontrivial lefschetz fibrations , , up to hurwitz equivalence , can be expressed as a product of two nontrivial positive factorizations of @xmath129 . ] it can not have any exceptional sections , i.e. sections of self - intersection @xmath37 , and thus it is not a blow - up of a pencil . motivated by this , stipsicz conjectured in the same article that every lefschetz fibration @xmath18 , if not a blow - up of a pencil , is a fiber sum of such , which amounts to having lefschetz pencils as building blocks of any lefschetz fibration via fiber sums . in @xcite , sato proved that an interesting genus@xmath6 lefschetz fibration constructed by auroux in @xcite , which could not be a fiber sum of nontrivial lefschetz fibrations , did not have any exceptional sections either . this remained as the only known counter - example until recently , where in @xcite , we obtained several other genus@xmath6 and @xmath350 counter - examples . the purpose of this section is to demonstrate the recipe of @xcite to generate such examples . we will do this while producing quick examples from a well - known relation in the mapping class group . we will then show that auorux s example can also be derived in this very scheme . for various background results that goes into this recipe , we advise the reader to turn to @xcite . let @xmath351 be the simple closed curves on @xmath352 as shown in figure [ scc_genus2surface ] , and @xmath353 denote the two boundary components with marked points @xmath354 . the chain relation of length @xmath16 @xmath355 in @xmath356 ( see ( * ? ? ? * proposition 4.12 ) ) , prescribes a triple @xmath357 , which is a genus@xmath6 lefschetz fibration @xmath358 with a pure @xmath6section @xmath43 that consists of two exceptional sections @xmath359 . it is well - known that @xmath360 is the @xmath361 surface blown - up twice , the symplectic canonical class of which is represented by @xmath362=[s_1 ] + [ s_2]$ ] in @xmath363 . @xcite [ lem_lantern_relation ] let the curves @xmath364 , pairs of arcs @xmath365 and points @xmath354 in @xmath366 be as shown in figure [ fig_lantern_relation ] , where @xmath367 are parallel to boundary components . denote the boundary components parallel to @xmath368 by @xmath3 . then the relation @xmath369 holds in @xmath370 ( whose elements restrict to identity along the four boundary components without marked points ) . substituting the subword on the right hand side of the above relation in the framed mapping class group ( of a surface that contains the above subsurface with marked boundary components ) with the subword on the left is then called a _ braiding lantern substitution_. its importance and relevance to our current discussion is due to our observation in @xcite that whenever the two marked boundary components correspond to two exceptional sections @xmath359 , we get a new exceptional @xmath6section @xmath371 after the substitution , which we view as a result of _ braiding _ @xmath293 and @xmath294 together . forgetting the two marked boundary components , one gets the usual lantern relation . in this case , the subword @xmath372 indicates that by clustering the corresponding lefschetz critical points on the same singular fiber , we can obtain a fiber _ component _ @xmath373 , which is a sphere of self - intersection @xmath374 . this @xmath373 , which we will call a _ lantern sphere _ , can be assumed to be symplectic with respect to a gompf - thurston form . remembering the two marked boundary components , we conclude that the exceptional classes @xmath293 and @xmath294 each intersect @xmath373 positively at one point . now , one can easily find a lantern sphere @xmath373 in the monodromy factorization of @xmath358 hit once by each exceptional section @xmath3 , @xmath4 . remarkably , this holds for _ any _ lantern sphere ( and there are many of them ; at least six disjoint ones @xcite ) . this is because for @xmath373 symplectic , the adjunction equality implies that its intersection with the canonical class @xmath375+[s_2]$ ] is @xmath6 , whereas each @xmath3 intersects the fibers positively . applying the braiding lantern substitution results in a new triple @xmath376 , a genus@xmath6 lefschetz fibration with an exceptional @xmath6section @xmath371 . as discussed in @xcite , an observation of gompf shows that @xmath377 is diffeomorphic to an ordinary blow - down of @xmath360 , so @xmath378 , which has only one exceptional class , already represented by @xmath371 . ( see ( * ? ? ? * corollary 3 ) . note that @xmath379 is not rational nor ruled . ) it follows that @xmath380 does not have any other exceptional _ sections_. on the other hand , it was shown by usher in @xcite that a nonminimal symplectic @xmath0manifold can not be a nontrivial fiber sum ( also see @xcite for a simpler proof for lefschetz fibrations ) , so the presence of @xmath371 also implies that @xmath380 can not be a fiber sum of any two nontrivial lefschetz fibrations . hence , we have obtained another example of a lefschetz fibration which can not arise from lefschetz pencils via blow - ups and fiber sums . [ [ aurouxs - genus2-fibration - with - an - exceptional-2section ] ] auroux s genus@xmath6 fibration with an exceptional @xmath6section ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ let @xmath381 and @xmath382 be simple closed curves in @xmath352 parallel to the boundary components containing @xmath383 and @xmath384 , respectively . we take non - separating simple closed curves @xmath385 , a path @xmath386 between @xmath383 and @xmath384 and a pair @xmath387 of paths connecting the two boundary components as shown in figure [ scc_genus2surface ] . let @xmath392 and @xmath393 . it is easy to see ( by the alexander method ( see ( * ? ? ? * . 2.3 ) ) , for example ) that @xmath394 is equal to @xmath395 $ ] , where @xmath396 $ ] is the mapping class of the hyperelliptic involution @xmath397 given in figure [ loop_in_quotientsurface ] . thus , the product @xmath399 is calculated as follows : @xmath400 \\ = & t t_3t_2t_1t_4t_3t_2(t_5t_4t_3t_2t_1 ) ( t_2t_1)^2(t_5t_4)^3 [ \iota ] \\ = & t t_3t_2t_1(t_5t_4t_3t_2t_1)t_5t_4t_3(t_2t_1)^2(t_5t_4)^3 [ \iota ] \\ = & t t_3t_2t_1(t_5t_4t_3t_2t_1)^2t_2t_1(t_5t_4)^3 [ \iota ] \\ ( t_5t_4t_3t_2t_1)^3(t_5t_4)^3 [ \iota ] \\ = & t ( t_2t_1)^3(t_5t_4t_3t_2t_1)^3 [ \iota ] \\ = & ( t_5t_4t_3t_2t_1)^6 [ \iota ] \\ = & t_{\delta_1}t_{\delta_2 } [ \iota ] , \end{aligned}\ ] ] where the last equality follows from the chain relation of length @xmath16 . we can naturally regard the mapping class @xmath401 as an element in @xmath402 , where @xmath403 is defined in ( * ? ? ? * .3.1 ) . by ( * ? ? * lemma 3.1 ) , the kernel of the homomorphism @xmath404 induced by the quotient map @xmath405 is generated by the class @xmath396 $ ] , where @xmath406 denotes the point @xmath407=[u_2 ] \in \sigma_2 ^ 2/\iota$ ] and @xmath408 consists of orientation preserving diffeomorphisms fixing @xmath406 ( resp . @xmath409 ) pointwise ( resp . setwise ) modulo isotopies fixing the same data . it is easy to see that the image @xmath410 is equal to the pushing map @xmath411 along the loop @xmath412 in figure [ loop_in_quotientsurface ] . the mapping class @xmath413 can also be regarded as an element in @xmath402 , and it is sent to @xmath411 by @xmath414 . thus , @xmath415 is contained in the kernel of @xmath414 . since @xmath415 interchanges the points @xmath383 and @xmath384 , this is equal to @xmath396 $ ] . in particular the following relation holds in @xmath416 : @xmath417.\ ] ] thus , the product @xmath418 is calculated as follows : @xmath419 t_{\delta_1}t_{\delta_2 } [ \iota ] \\ = & t_{\delta_1 } t_{\delta_2 } t_{\delta_2}t_{\delta_1 } [ \iota ] [ \iota ] \\ = & t_{\delta_1}^2 t_{\delta_2}^2.\end{aligned}\ ] ] this completes the proof . as we explained in section [ s : factorization multisection ] , we can regard the surface @xmath352 as a subsurface of @xmath420 by capping @xmath421 by two disks with the centers @xmath422 . the pair of paths @xmath423 and the path @xmath185 respectively give rise to a simple closed curve in @xmath420 going through @xmath244 and @xmath424 and a simple path between @xmath244 and @xmath424 . to simplify the notation , we use the same symbols @xmath423 and @xmath185 to represent these curves . we also denote the dehn twist along @xmath425 by @xmath426 . now by proposition [ t : lift_auroux fibration ] , we obtain the following factorization in @xmath427 : @xmath428 which prescribes a triple @xmath429 where @xmath430 is a genus@xmath6 lefschetz fibration with a sphere @xmath6section @xmath293 by theorem [ mainquote ] . under the forgetful homomorphism @xmath431 this positive factorization maps to the monodromy factorization of auroux s aforementioned genus@xmath6 lefschetz fibration given in @xcite . on the other hand , we can calculate the self - intersection number of @xmath293 using the positive factorization in the framed mapping class group we had in proposition [ t : lift_auroux fibration ] ( which of course is a lift of the monodromy factorization @xmath432 and theorem 1.1 of @xcite . hence @xmath429 is auroux s genus@xmath6 lefschetz fibration , where @xmath293 is the exceptional @xmath6section . we are now ready to show that @xmath429 can be reproduced using our recipe discussed in the previous subsection . let @xmath433 denote the genus@xmath6 lefschetz fibration with a pure @xmath6section @xmath434 , which is a disjoint union of two exceptional sections , as prescribed by the @xmath16chain relation @xmath435 in @xmath427 . [ t : auroux fibration and chain fibration ] the triple @xmath151 , where @xmath348 is auroux s genus@xmath6 fibration with the exceptional @xmath6section @xmath293 , is equivalent to a triple obtained from @xmath433 by a single braiding lantern substitution , followed by a perturbation of the @xmath6section . we first prove that the factorization @xmath435 in @xmath427 is hurwitz equivalent to the following factorization : @xmath436 the factorization can be changed by elementary transformations as follows ( in each line elementary transformations are applied to the underlined part to obtain the next line ) : @xmath437 by lemma [ lem_lantern_relation ] , @xmath440 is equal to @xmath441 . applying the substitution by this relation to the underlined part in , we obtain the following factorization : @xmath442 where the equivalence above holds since @xmath443 is equal to @xmath444 . according to ( * remark 3.9 ) , we can perturb the @xmath6section of the fibration corresponding so that it is away from the lefschetz critical point corresponding @xmath445 , and the resulting fibration with a @xmath6section has the following factorization : @xmath446 the last factorization coincides with the monodromy factorization of @xmath429 in the equation above . we have thus derived @xmath429 from @xmath357 , after a braiding lantern substitution , followed by a perturbation of the resulting @xmath6section to move one of its branched points off the lefschetz critical locus while applying hurwitz moves for lefschetz fibrations with multisections in various steps of the proof . d. auroux , _ fiber sums of genus-@xmath6 lefschetz fibrations _ , turk . j. math . * 27*(2003 ) , 110 . r. i. baykur , _ minimality and fiber sum decompositions of lefschetz fibrations , _ proceedings of the ams ( to appear ) ; http://arxiv.org/abs/1407.5351 . r. i. baykur and k. hayano _ multisections of lefschetz fibrations and topology of symplectic @xmath0manifolds _ , preprint ; http://arxiv.org/abs/1309.2667 s. k. donaldson , _ lefschetz pencils on symplectic manifolds _ , j. differential geom . * 53*(1999 ) , no.2 , 205236 s. k. donaldson and i. smith , _ lefschetz pencils and the canonical class for symplectic four - manifolds _ , topology * 42*(2003 ) , no . 4 , 743785 c. j. earle and j. eells , _ a fibre bundle description of teichmller theory _ , j. differential geom . * 3*(1969 ) , 1943 . b. farb and d. margalit , _ a primer on mapping class groups _ , princeton university press , 2011 r. e. gompf and a. i. stipsicz , _ 4-manifolds and kirby calculus _ , graduate studies in mathematics * 20 * , american mathematical society , 1999 . a. kas , _ on the handlebody decomposition associated to a lefschetz fibration _ , pacific j. math . * 89*(1980 ) , 89104 . li , _ smoothly embedded spheres in symplectic @xmath0manifolds _ , proc . soc . , * 127*(1999 ) , no 2 , 609613 y. matsumoto , _ lefschetz fibrations of genus two - a topological approach _ - , proceedings of the 37th taniguchi symposium on topology and teichmller spaces , ( s. kojima , et . al . , eds . ) , world scientific , 1996 , 123148 . y. sato , _ @xmath6-spheres of square @xmath37 and the geography of genus-@xmath6 lefschetz fibrations _ , j. math . tokyo , * 15*(2008 ) , 461491 . i. smith , _ geometric monodromy and the hyperbolic disc , _ q. j. math . 52 ( 2001 ) , no . 2 , 217228 . a. i. stipsicz , _ indecomposability of certain lefschetz fibrations _ , 129*(2001 ) , 14991502 m. usher , _ minimality and symplectic sums , _ int . res . not . 2006 , art . id49857 , 117 .

in this article , we characterize isomorphism classes of lefschetz fibrations with multisections via their monodromy factorizations . we prove that two lefschetz fibrations with multisections are isomorphic if and only if their monodromy factorizations in the relevant mapping class groups are related to each other by a finite collection of modifications , which extend the well - known hurwitz equivalence . this in particular characterizes isomorphism classes of lefschetz pencils . we then show that , from simple relations in the mapping class groups , one can derive new ( and old ) examples of lefschetz fibrations which can not be written as fiber sums of blown - up pencils .

genetic evidence so far establishes that at least six mammalian tetraspanins ( shaded in fig . two themes emerge : the importance of tetraspanin large extracellular loops , and the importance of tetraspanin complex formation with other proteins . mutation of peripherin / rds leads to several retinal diseases in humans ( kohl et al . , 1998 ) , and targeted deletion of peripherin / rds from mice leads to disrupted photoreceptor morphogenesis ( sanyal et al . , 1980 ) . most of the peripherin / rds mutations that cause human disease , including the vast majority of known missense mutations , are located within the large extracellular loop ( kohl et al . , 1998 ) . the related tetraspanin protein , rom , is less essential , but nonetheless also important for photoreceptor viability and morphogenesis in mice ( clarke et al . , 2000 ) . disease - causing mutations prevent peripherin and rom from forming homo- and heterotetrameric core complexes that link together into higher order structures required for photoreceptor disk formation ( loewen and molday , 2000 ; loewen et al . , 2001 ) . the human tetraspanin tm4sf2/a15 , when inactivated by a chromosomal translocation ( x;2 ) , by a premature stop codon , or by a point mutation ( p172h ) , is associated with mental retardation ( zemni et al . , 2000 ) . appropriately , the tm4sf2 tetraspanin is highly expressed in areas of the brain involved in learning and memory ( zemni et al . , 2000 ) . the p172h mutation demonstrates again an essential role for the large extracellular loop of a tetraspanin . other than its association with ptdins 4-kinase ( yauch and hemler , 2000 ) , little is yet known regarding the biochemistry of tm4sf2/a15 . targeted deletion of cd81 in mice resulted in impaired b cell functions ( maecker and levy , 1997 ; miyazaki et al . , 1997 ; tsitsikov et al . , 1997 ; deng et al . , 2000 ) , and enhanced t cell proliferation ( miyazaki et al . , reduction in levels of cd19 in cd81 null mice confirms the importance of cd81-cd19 signaling complexes in b cells . associations with molecules such as cd4 and cd8 could contribute to the signaling role of cd81 on t cells ( levy et al . cd9 null mice produce oocytes that are deficient in sperm egg fusion ( miyado et al . , 2000 ; le naour et al . , 2000 ) , indicating that oocyte cd9 plays a key role in the fusion process , or in the binding of sperm fertilin / adam2 protein to eggs . the occurrence of cd9-61 complexes is consistent with 61 integrin also participating in fertilization ( takahashi et al . , 2001 ) . however , this is controversial because normal fertilization was observed in 6 integrin deficient mice ( miller et al . , 2000 ) . besides lymphocytes and oocytes , many other cells and tissues ( such as brain ) show high expression of cd81 and cd9 ( schmidt et al . , 1996 ; sullivan and geisert , 1998 ) . thus , the phenotypes of the cd9 and cd81 null mice are less dramatic than might have been expected . disruption of cd37 in mice yielded a relatively subtle alteration in b cell igg production , and a t cell dependent immune response deficiency that was especially obvious under suboptimal stimulation conditions . thus , cd37 regulates b cell humoral responses as well as t cell b cell interactions ( knobeloch et al . , 2000 ) . the biochemical basis for cd37 functions on b cells is unclear , but could involve cd37 associations with cd19 , cd21 , mhc class ii molecules , or other tetraspanins ( angelisova et al . , 1994 ) . other genetic evidence for tetraspanin functions comes from flies and fungi . among the 37 drosophila tetraspanins , the only one so far identified in a genetic screen is late bloomer , a facilitator of synapse formation ( kopczynski et al . , 1996 ) . complementation and functional overlap among the many drosophila tetraspanins likely accounts for the absence of additional genetic evidence . in another example , the rice blast fungus m. grisea contains a tetraspanin - like protein pls1p ( with 10/26 key residues shown in fig . 1 ) that is essential for penetration of the fungus into host leaves ( clergeot et al . , drosophila and m. grisea tetraspanins display functions ( synapse formation and fungal penetration ) resembling the membrane organizing and cell migration and invasion functions of mammalian tetraspanins ( boucheix and rubinstein , 2001 ) . early studies pointed to the potential of tetraspanins to associate with a wide variety of partner proteins in a tetraspanin web . not only do tetraspanins associate with each other , but they also associate with many ig superfamily proteins , proteoglycans , complement regulatory proteins , integrins , growth factors , growth factor receptors , and signaling enzymes ( for review see boucheix and rubinstein , 2001 ) . assembly of the tetraspanin web is based on multiple levels of interactions ( serru et al . , 1999 ; stipp et al . these interactions are direct , and resist disruption by detergents such as brij96 , digitonin , and/or triton x-100 ( see examples below ) . second level interactions are indirect , more numerous , and much more sensitive to disruption by brij96 , digitonin , and/or triton x-100 . soluble second level complexes ( maintained in detergents such as brij56 , brij99 , and chaps ) arise as tetraspanins associate with each other , and thereby link together multiple primary complexes . tetraspanin cd151 palmitoylation does not markedly alter tetraspanin complex density or decrease detergent solubility but nonetheless does plays a role during the assembly of level 2 complexes ( yang et al . , 2002 ) . a third level of tetraspanin complex assembly occurs in the context of insoluble complexes , resistant to detergents such as chaps , brij-99 , or brij-58 . for example , in 1% brij58 , brij99 , or chaps , tetraspanin complexes become large ( excluded from sepharose 4b or 6b gel filtration columns ) and light ( appearing in the light membrane resistance of tetraspanin complexes to detergent solubilization is consistent with their partial lipid raft - like properties ( yashiro - ohtani et al . , 2000 ; direct tetraspanin ganglioside association , as seen by covalent cross - linking of gm3 to cd9 ( ono et al . , 2001 ) , may also contribute to stabilization of detergent - resistant level 3 tetraspanin complexes . primary tetraspanin interactions within the tetraspanin web are characteristically specific ( limited to only a few types of tetraspanins ) , proximal ( captured by covalent cross - linking ) , soluble ( included within gel filtration columns , present in high density sucrose gradient fractions ) , and of reasonably high stoichiometry ( i.e. , > 50% in the complex ) . also , it is reassuring to have evidence that the partner molecules are working together functionally . a few examples of level one interactions are highlighted here . in the urinary tract , two tetraspanins ( uroplakin ia and ib ) each associates directly with nontetraspanin type i transmembrane proteins ( uroplakins ii and iii , respectively ) , as confirmed in covalent cross - linking experiments ( wu et al . , 1995 ) . supporting the relevance of the uroplakin ib - iii complex , production of mice deficient in uroplakin iii resulted in global anomalies in the urinary tract , coupled with markedly altered expression , processing , and targeting of the tightly associated tetraspanin uroplakin ib ( hu et al . , 2000 ) . although the uroplakin ia - ii and uroplakin ib - iii complexes ( like the peripherin rom complexes mentioned above ) each acts as a discrete primary structural unit , all four components form a tightly packed structure , essential for urothelial plaque formation ( liang et al . , 2001 ) . for the cd9 and cd81 tetraspanins , the most robust protein partners yet found are type 1 transmembrane proteins named ewi - f and ewi-2 ( also called pglr , cd9p-1 , and fprp ) . ewi-2 and ewi - f , together with ewi-3 and ewi-101 ( cd101 ) , comprise a novel subfamily of structurally related immunoglobulin superfamily proteins that share a specific glu - trp - ile ( ewi ) motif in their second ig domain ( clark et al . , 2001 ; charrin et al . , 2001 ; stipp et al . , 2001a , b ) . tetraspanins cd9 and cd81 each can associate directly ( as captured by covalent cross - linking ) with either ewi-2 or ewi - f in distinct complexes , and with high stoichiometry ( 70100% ) . also , associations occurred in the soluble phase , were well maintained in detergents such as digitonin , brij 96 , and triton x-100 , and were not sensitive to cholesterol depletion ( charrin et al . further studies are now needed to evaluate how ewi proteins might influence various cd81 and cd9 functions in brain , liver , developing muscle , nervous system , oocytes , lymphocytes , or elsewhere . for example , ewi proteins could potentially modulate cd9 effects on sperm egg fusion ( le naour et al . , 2000 ; miyado et al . , 2000 ) , myoblast fusion ( tachibana and hemler , 1999 ) , diphtheria toxin binding ( cha et al . , 2000 ) , or the mitogenic activities of membrane bound forms of hb - egf ( nakamura et al . , 2000 ) , and tgf ( shi et al . , 2000 ) . likewise , ewi proteins need to be examined for modulation of cd81 functions in the brain ( kelic et al . , 2001 ) , and during hepatitis c virus binding ( pileri et al . , 1998 ; higginbottom et al . , 2000 ) , myoblast fusion ( tachibana and hemler , 1999 ) , and lymphocyte signaling ( levy et al . , regard , strong association of ewi-2 with cd81 on b cell lines ( clark et al . , 2001 ) would seem likely to influence the well - characterized cd81-cd19-cd21 signaling complex on b cells ( levy et al . , 1998 ) . among the tetraspanins , cd151 stands out because of its stable association with 100% of cellular 31 integrin in several cell lines , and the majority of 6 integrins on a lymphoid cell line ( serru et al . , 1999 ; the association of cd151 with the 31 integrin can be captured by covalent cross - linking and requires the cd151 large extracellular loop , as well as the integrin 3 subunit extracellular stalk region ( yauch et al . , 2000 ; , anti - cd151 antibody inhibited neurite outgrowth when 3 integrin was engaged with laminin-5 ligand , but not when other integrin ligands were used and 31 was unengaged ( stipp and hemler , 2000 ) . as part of a cd15161 complex , cd151 exerts a major influence on 61 integrin dependent morphogenesis when fibroblast and endothelial cells are grown on basement membrane matrigel ( zhang et al . , 2002 ) . in particular , mutation of the short cooh - terminal tail of cd151 completely abolished 61-dependent mobilization of fibroblasts into a meshwork of cellular cables . the functional relevance of specific cd151 association with 64 integrin in hemidesmosomes remains to be established ( sterk et al . however , in a kidney epithelial cell line that lacks 3 integrin , cd151 associated predominantly with 64 and markedly influenced cellular morphology . in each of the above - mentioned studies , the cd151 molecule had minimal effects on 3 or 6 integrin mediated cell adhesion , but rather modulated the subsequent outside - in functions of the integrins . although molecular details are still sketchy , tetraspanins are reported to alter integrin - dependent signaling through focal adhesion kinase , in parallel with rearrangement of the cortical actin cytoskeleton ( berditchevski and odintsova , 1999 ) . although the extracellular domain of cd151 is required for integrin association , it is the intracellular and/or transmembrane domains that regulate cell morphology ( zhang et al . , 2002 ) and associate with signaling enzymes such as conventional pkc isoforms ( zhang et al . , 2001 ) . thus , cd151 may function as a transmembrane linker ( hemler , 1998 ) . such a function helps to explain how the extracellular domain of the integrin 3 subunit would be involved in the recruitment of intracellular pkc and intracellular phosphorylation of the 3 cytoplasmic tail ( zhang et al . , because other tetraspanins also use extracellular domains to associate with partner proteins , and cytoplasmic or transmembrane domains to associate with intracellular signaling enzymes ( boucheix and rubinstein , 2001 ) , the transmembrane linker theme could extend well beyond the cd15131 complex . this review highlights specific details regarding a few tetraspanins , which may represent emerging trends , that could be extrapolated to many other tetraspanins . however , many questions remain . for example , it is not clear why several tetraspanins have been associated either positively ( c0-o29 and cd151 ) or negatively ( cd9 , cd63 , and cd82 ) with tumor cell metastasis ( boucheix et al . , 2001 ) . possibly , the tendency of multiple tetraspanins to localize into endothelial and epithelial cell cell junctions ( ynez - m et al . , 1998 , 2001 ) will provide a context in which to influence tumor cell behavior . for example , detailed brain analyses and dna array screens are turning up tetraspanins with increasing frequency . in addition , advances in protein identification by mass spectrometry have accelerated the rate of discovery of tetraspanin - associated proteins . as more of the specific level 1 and 2 tetraspanin partners are identified , and the rules for level 3 membrane microdomain assembly are clarified , the current tetraspanin morass should gradually be revealed as a coherent and intricate tetraspanin network . a general working hypothesis is that tetraspanins act as molecular facilitators or transmembrane linkers , using intracellular and/or transmembrane domains to recruit key signaling enzymes , whereas large extracellular loops engage other transmembrane proteins in specific lateral associations ( hemler , 1998 ; zhang et al . , 2001 ) . in this manner , tetraspanins may assemble a novel type of protein / lipid microdomain with considerable functional potential .

relatively little attention has been given to the large family of abundantly expressed transmembrane proteins known as tetraspanins . now , the importance of tetraspanins is strongly supported by emerging genetic evidence , coupled with new insights into the biochemistry and functions of tetraspanin protein complexes .

sinus node dysfunction ( snd ) is a relatively common cardiac condition in the elderly . standard and long - term electrocardiographical recording may exhibit persistent bradycardia , alternating bradycardia tachycardia , sinus pauses , or sinus arrest . in this context , the appearance of ventricular hyperexcitability is often a bradycardia - induced arrhythmia,1 and it may mask the classical electrocardiographical presentation of snd ( concealed snd ) . pharmacological autonomic blockage is sometimes used to unmask a concealed form of snd , also it may help to distinguish between intrinsic and extrinsic forms of snd . in this paper , we present a symptomatic patient with a concealed form of snd , in whom atropine testing yielded a junctional rhythm with a nearly total disappearance of premature ventricular complexes ( pvcs ) . the appearance of accelerated junctional rhythm is a paradoxical effect of atropine , and discussion was made according to the literature data . the patient has given his consent for publication of his medical information in this case report . electrocardiogram and electrical monitoring showed sinus rhythm with persistent ventricular hyperexcitability in the form of ventricular bigeminy : monomorphic pvc with fixed coupling interval and fixed post - pvc cycle length ( fig . moreover , pvcs were non - efficient hemodynamically yielding a radial pulse estimated at ~30 bpm . cardiac echogram revealed no structural heart disease . also a coronary angiogram revealed no significant coronary artery disease . after a short - term ( 48 hours ) beta - blocker therapy in an attempt to reduce ventricular ectopy , the patient was referred to the electrophysiologist who suspected a concealed snd as initial diagnosis . a bedside pharmacological testing with 0.5 mg atropine ( bolus ) was applied ; there was a sinus arrest with a junctional accelerated rhythm within 40 seconds , along with relative disappearance of ventricular ectopy ( fig . the patient was reluctant to any further invasive testing ( electrophysiological testing ) , and the diagnosis of concealed snd was retained ; accordingly , a dual chamber pacemaker was implanted with a programmed basic rate at 60 bpm . it allowed total disappearance of symptoms and nearly complete fading of ventricular ectopy ( fig . concealed snd with bradycardia - induced pvcs was the most probable diagnosis initially retained given the absence of structural heart disease and the response to heart rate acceleration yielding nearly complete fading of ventricular ectopy . the second diagnostic hypothesis was primary ventricular hyperexcitability with consecutive post - pvc pauses , probably expanded by retrograde conduction . however , the response to atropine with fading of pvcs is rather suggestive of concealed snd with secondary ventricular hyperexcitability ; in this context , the mechanism of pvcs is either triggered activity or increased automaticity.1 the concept of concealed snd is not quite new2 ; however , it is important to recall this phenomenon given its rare and atypical presentation . of note , beta - blocker therapy was given in an attempt to suppress pvcs . also it could have worsened the bradycardia ; patients with snd have frequently a compensatory sympathetic regulation to improve the impaired intrinsic automaticity , and beta - blocker therapy may suppress this adrenergic compensatory mechanism.3 snd may be totally asymptomatic , and pacing indication is only recommended in symptomatic patients ; herein the decision for pacing was not only to suppress the symptoms but also to reduce / suppress the related ventricular hyperexcitability . the absence of retrograde p waves when a junctional rhythm appeared despite atropine administration favors this hypothesis4 ; an electrophysiological study ( non - performed because of patient reluctance ) could have confirmed this hypothesis . the occurrence of paradoxical sinus arrest is already documented with atropine , and the exact mechanism is poorly elucidated5,6 ; however , many assumptions have been proposed : ( 1 ) atropine with its vagolytic effect may exert a stress test on the p cells of the sinus node ( already diseased in snd ) , and this may yield a sinus arrest ; ( 2 ) atropine at low doses ( 0.5 mg ) may result in paradoxical vagotonic effect at the level of the sinoatrial node and a vagolytic effect at the level of the atrioventricular node with consequently the appearance of junctional rhythm ; and ( 3 ) atropine may lead to peripheral vasodilatation with hypotension , and a consecutive reflex hypervagotonia may occur ; the phenomenon is similar to the cardioinhibitory or vasodepressive response observed with drug challenge during tilt testing . also it is similar to the phenomenon of sinus arrest observed during induction of general anesthesia when associated with massive peripheral vasodilatation.6 at low doses ( 0.5 mg ) , atropine exerts a vagotonic stimulation of the central nervous system with probable cholinesterase inhibition , and this phenomenon is thought to be a possible cause of the paradoxical effect of atropine.5 at higher doses ( 1 mg ) , the central vagotonic effect of atropine may be masked by its muscarinic blockade.7 concealed snd may present as ventricular hyperexcitability , and such atypical presentation can compromise the diagnostic and therapeutic processes . paradoxical response to atropine in snd may consist of sinus arrest and junctional escape rhythm ; such paradoxical effect may be related to either primary central vagotonic effect of atropine or secondary reaction related to the vasodilatatory effect of atropine .

a 78-year - old male patient presented with repetitive fainting episodes . his electrocardiogram showed sinus rhythm with persistent ventricular bigeminy . concealed sinus node dysfunction ( snd ) with consecutive bradycardia - induced ventricular hyperexcitability was suspected . pharmacological testing with atropine resulted in accelerated junctional rhythm along with nearly total disappearance of the ventricular ectopy . the diagnosis of snd was retained , a dual chamber pacemaker was implanted , and consequently , ventricular hyperexcitability disappeared . the junctional rhythm was a paradoxical effect of atropine , and many explanations were provided . discussion was made accordingly taking into account relevant data from the literature .

the laser geodynamic satellite experiment ( lageos-3 ) is a joint usaf , nasa , and asi proposed program to measure , for the first time , a quasi - stationary property of the earth its gravitational magnetic dipole moment ( gravitomagnetism ) as predicted by einstein s theory of general relativity . this gravitomagnetic field causes local inertial frames to be dragged around with the earth at a rate proportional to the angular momentum of the earth , and inversely proportional to the cube of the distance from the center of the earth . thus the line of nodes of the orbital plane of lageos-3 precesses eastward at @xmath0 . although in this example the frame dragging effect is small compared to the torque on the orbital plane due to the oblateness of the earth , it is an essential ingredient in the dynamics of accretion disks , binary systems , and other astrophysical phenomena @xcite . today , almost eighty years after einstein introduced his geometric theory of gravity , we have just begun to measure to verify his gravitation theory . of no less stature than the `` tide producing '' @xmath1 `` electric component '' of gravity is the inertial - frame defining `` magnetic component '' of gravitation @xmath2 . to see this force in action : first , inject a satellite into a polar orbit about an earth - like mass idealized as not spinning with respect to the distant quasars . the satellite will remain in orbit in a continuous acceleration towards the center - of - mass of the attracting body under the influence of the newtonian @xmath3 force , and its orbital plane will remain fixed in orientation with respect to distant quasars . second , spin the central body , giving it angular momentum , and follow the trajectory of the satellite . its orbital plane will experience a torque along the central body s rotation axis . the orbital plane will undergo a precessional motion in the direction of the central body s rotation . the mass in motion of the central body , or `` mass current '' , produces a dipole gravitational field the gravitomagnetic field . in the case of a satellite orbiting at two earth radii , the orbital plane will precess about the body axis of the earth at approximately @xmath4 . this is the lense - thirring effect @xcite . the lense - thirring force has never been directly measured . a measurement of this gravitomagnetic force can be compared to the pioneering work of michael faraday on the measurement of the magnetic force between two current - carrying wires . however , the laboratory setting for this gravity measurement will be the 4-dimensional curved spacetime ( approximately kerr ) geometry enveloping the earth . the idea behind the lageos gravity measurement is simple . whereas the everitt - fairbanks experiment ( gravity probe - b ) proposes putting a gyroscope into polar orbit @xcite , the ciufolini lageos-3/lageos-1 experiment @xcite proposes the use of the orbital planes themselves as a gyroscope . in 1976 nasa launched the lageos-1 satellite , a totally passive @xmath5 diameter ball of aluminum with @xmath6 retro - reflecting mirrors embedded in its surface . ( there are numerous globally - located laser tracking stations to observe lageos - type satellites . ) lageos-1 was injected into a two earth - radii circular orbit at an inclination of @xmath7 . due to the oblateness of the earth , the orbital plane rotates at a rate of @xmath8 . this torquing can only be modeled to @xmath9 which is not accurate enough to measure the @xmath10 gravitomagnetic force . the idea of ciufolini is to launch another lageos satellite ( lageos-3 ) into an orbit identical to that of lageos-1 , except that its inclination is supplementary ( @xmath11 ) . this proposed orbital plane will rotate in the opposite direction , _ i.e. _ , @xmath12 . the intersection of the two ( lageos-1 , lageos-3 ) orbital planes will sweep out a `` tandem - generated gyro plane '' ( fig . [ figure1 ] ) . the utilization of two satellites cancels out many of the large precessional effects due to mass eccentricities of the earth , providing a plane inertial enough for a measurement , accurate to five percent ( or better ) , of the `` magnetic component '' of gravity . = the success of the lageos experiment hinges upon the detection of a @xmath10 eastward drift of the line of nodes of the two satellites . a strong effort is now underway to model the orbital and spin dynamics of these satellites , and to make an assessment of the uncertainties these will add to the desired measurements . encapsulated in table [ table1 ] are the five major classes of errors in this experiment : ( 1 ) geopotential ( other than even zonals ) and tides , ( 2 ) earth radiation pressure , ( 3 ) uncertainty in other relativistic effects , ( 4 ) earth and solar - induced thermal forces , and ( 5 ) even zonal geopotentials ( per @xmath13 inclination injection error ) . due to the recent gem - t1 improvements in the earth s zonal harmonics , the errors due to solid - earth tides have been significantly reduced , and are now potentially smaller than those due to surface effects @xcite . these surface effects ( _ e.g. _ , yarkowsky thermal drag , neutral and charged particle drag ) cause a change in the nodal precession of the satellite , thus contributing to what will be potentially the largest source of error in the lageos-3 measurement of the gravitomagnetic effect . in modeling these surface forces , in particular the yarkowsky thermal drag ( also referred to as the rubincam effect ) due to the satellite s differential heating and delayed reradiation , the behavior of the spin vector of the satellite is of crucial importance . that the uncertainties induced by the surface forces on lageos are on the order of 4% , out of a 6% experiment , makes such a theoretical modeling of paramount importance . with this in mind , we undertake in this paper a theoretical model of the spin dynamics of lageos - type satellites , and compare our results with observational data . we must emphasize that we are looking for qualitative , not quantitative , results . we do not intend to predict the exact magnitude and direction of the spin vector at any particular instant . instead , we desire a rough estimate of its magnitude , and whether its behavior is predictable or chaotic . we seek to answer questions of the sort : `` in the asymptotic limit , does the satellite tidally lock , tumble , or have some other behavior ? '' previous studies of the spin dynamics of the lageos-1 satellite @xcite were valid only for spin rates much larger than the orbital frequency . today , however , the spin of the satellite , decaying with a three - year time constant , is rapidly approaching the orbital period . we therefore require an analysis in the low frequency regime . unlike the earlier analysis which dealt with orbit - averaged quantities , we will solve numerically the full set of dynamical equations . as we will show , while the low frequency regime exhibits complex behavior , the asymptotic state of this forced , damped system appears to be tidally locked . in this paper we will examine the spin - orbit resonance phase and discuss the asymptotic state of the spin of the satellite . it is the goal of this research to provide an optimum strategy for the measurement of the spin dynamics of the lageos satellites in support of the proposed gravity measurement . in addition , we use our theoretical model to propose an optimum orbital injection procedure for lageos-3 : it is our opinion that the lageos-3 satellite should be injected into the orbital plane with as large a spin rate as possible . our results provide the first analysis of the asymptotic spin dynamics of the lageos satellite . previous calculations were unable to analyze the spin - orbit resonances of the satellite , nor its asymptotic behavior , which will play a crucial role in the experiment . we demonstrate in this paper that the lageos-1 satellite will be sufficiently predictable to support the gravitomagnetic measurement . . * the latest error budget for the lageos-3 lense - thirring experiment*. errors in geopotential and tides reflect improvement over gem - t1 . uncertainty in the thermal forces depends mainly on knowledge of spin - axis motion . the even zonal geopotential error calculation assumes less than @xmath14 inclination injection error . the random and stochastic error estimate can accommodate seasonal variations in low degree spherical harmonics of the geopotential . [ cols="<,<,>",options="header " , ] it is rather interesting that after 36 years the spin dynamics of passive satellites is once again important to the field of astrodynamics . in 1957 vinti @xcite analyzed the spin dynamics of a non - ferromagnetic spherical satellite in the earth s magnetic field , which was then of critical importance to the alignment of antennas . today we perform the same analysis on a slightly oblate satellite , of critical importance to the first measurement of the magnetic component of gravity , as predicted by einstein . there are many factors to consider when analyzing the spin dynamics of an oblate , metallic satellite orbiting in the gravitational and magnetic fields of the earth . the most prominent effect is the torqueing due to the gravitational field of the earth . this arises from the oblateness of the satellite , with the oblateness of the earth producing a negligible contribution that can be added to our calculations as an adiabatic correction . if the satellite s ( bulging ) equatorial plane lies in the plane of orbit , no such torques are possible . however , when the satellite is not placed exactly in such a position , gravitational torques will arise . in an effort to model these torques , we consider the situation of an oblate spheroid in orbit around a point mass . as was done by bertotti and iess , we parallel the development in goldstein @xcite . bertotti and iess s analysis of the effects of gravity on the spin dynamics of the oblate satellite , which resulted in predicting a _ chaotic _ spin dynamics of arbitrarily large amplitude in the obliquity at late times , is not appropriate for small rates of spin . their prediction is based on the `` hipparcos '' formula for the rate of precession @xmath15 of an oblate satellite in the inhomogeneous gravity field of the earth @xmath16 where @xmath17 is the orbital angular velocity , @xmath18 is the satellite spin rate , @xmath19 is the obliquity angle of the satellite ( the angle between @xmath20 and the normal to the orbital plane ) and @xmath21 is the satellite s oblateness . here @xmath22 and @xmath23 are the principal moments of inertia ( the principal direction corresponding to @xmath22 is assumed to be that of @xmath20 and coincides , by assumption , with the symmetry axis of the oblate satellite ) . it is argued by bertotti and iess that , since @xmath24 , the gravitational precession in the asymptotic limit of small @xmath25 becomes very fast and may make the spin dynamics chaotic . this conclusion is based upon a misunderstanding . we have shown , via a careful analysis of assumptions underlying the `` hipparcos '' formula , that even in the approximation commonly used in deriving the formula ( averaging of the gravitational potential over the satellite orbit , dipole cutoff of the multipole decomposition , _ etc . _ ) eqn . ( [ 1 ] ) can only be used when @xmath26 _ i.e. _ , when the spin rate of the satellite is much greater than its orbital angular velocity . the latter restriction is easy to overcome , and the corrected equation for @xmath15 is @xmath27 this equation imposes a bound on @xmath28 : @xmath29 which makes it clear that the rate of precession can not grow to cause chaoticity of the satellite spin dynamics . a subsequent qualitative investigation @xcite by chris fuchs has shown that when magnetic forces are included in the picture the precession rate remains bounded , and should be much smaller than @xmath17 . another conclusion reached in the course of our analysis has been that , when both gravitational and magnetic forces are taken into account , the nutation , although bounded in its amplitude , does not disappear completely even in the asymptotic limit . the value of these results , however , is limited by the fact that they do not yield the exact bounds , nor do they provide any information on the time scale to reach the asymptotic limit . however , they do clearly show that chaoticity of the lageos spin dynamics caused by an unbounded growth of gravitationally - induced precession can not occur . another important factor governing the evolution of the spin vector is the interaction of the metallic core of the satellite with the magnetic field of the earth . the lageos satellite @xcite is composed of two aluminum hemispheres bolted together , with a brass cylindrical core along its body axis ( the original axis of spin ) ( fig . [ figure2 ] ) . the spinning of this metallic object in the magnetic dipole field of the earth ( and the motion through that field ) will cause eddy currents within the satellite , which will in turn cause dissipation through joule heating and a slowdown of the spin , and furthermore will cause torques on the spin vector . these torques can be understood as the interaction of the magnetic dipole , caused by the induced eddy currents , with the magnetic field of the earth . in modeling this effect , we have treated a uniform , spherical object in the orbit of a perfect magnetic dipole . here we are concerned with a simple qualitative analysis of the spin dynamics of lageos , as the complexity of the true satellite geometry prohibits us from a precise model of the eddy current distribution . our theoretical model permits us to analyze arbitrary inclinations of the orbital plane to the earth s magnetic dipole axis . the results presented in this paper correspond to a retrograde @xmath30 orbit . = the problem of a spinning metallic sphere in a constant magnetic field has been treated by landau and lifshitz @xcite , and we avail ourselves of their results . for our purposes , we ignore the torques caused by the changing magnetic field due to the orbit ( as opposed to spin ) of the satellite . these torques can be shown to be negligible until asymptotically late stages of motion , and have no qualitative effects upon the dynamics . the source of many of the difficulties in doing analyses of such orbiting , spinning bodies lies in the involved coordinate systems needed to describe their motion . thus , it is important at this point to give a brief description of the coordinates we will use in this paper . in our analysis of the spin dynamics of the lageos satellite we found it convenient to introduce the following four coordinate systems : * 1 . * _ the orbit - centered inertial frame ( oci ) @xmath31 . _ here the @xmath32-axis is oriented along the normal to the orbital plane of the satellite ( @xmath33 coinclination ) . the @xmath34-axis is defined to be the intersection of the orbital plane and the earth s equatorial plane , and the origin is the center of mass of the earth . we have assumed here that this frame is inertial , and have not included the secular drag of the line - of - nodes of the orbital plane due to the oblateness of the earth . this @xmath35 precession can be included at the end of our analysis as an adiabatic correction , and again has no qualitative effects upon the dynamics . _ the earth - centered inertial ( eci ) reference frame @xmath36_. here the @xmath37-axis is aligned with the body axis of the earth . the @xmath38-axis lies in the earth s equatorial plane at zero degrees longitude , and the origin coincides with the center of the earth . * 3 . * _ the body frame ( non - inertial ) @xmath39 . _ the origin is at the center of the satellite , and the axes correspond to a set of principal axes . the satellite is assumed to be a slightly oblate ( @xmath40 ) spheroid of brass , and the @xmath41-axis is aligned along its body axis . the @xmath42 and @xmath43 axes are an arbitrary fixed set of orthogonal axes spanning the equatorial plane of the satellite . in our calculations , the body axis is related to the orbit - centered frame through the three euler angles @xmath19 , @xmath44 , and @xmath45 . the nutation angle @xmath19 is the angle between @xmath41 and @xmath32 , while the angle of precession @xmath44 is the angle between the @xmath34-axis and the line of nodes ( the intersection of the orbital plane and the equatorial plane of the satellite ( @xmath42-@xmath43 plane ) ) . the spin angle @xmath45 is the angle between the line of nodes and the @xmath42-axis . * 4 . * _ the landau - lifshitz ( non - inertial ) coordinate system @xmath46 . _ the @xmath47-axis is aligned along the instantaneous angular momentum vector of the satellite ( @xmath48 ) . the @xmath49-axis is picked so that the instantaneous magnetic field ( @xmath50 ) at the satellite lies in the @xmath51 plane . note that @xmath47 need not be aligned with the body axis of the satellite , and in fact , during the asymptotic behavior of the satellite they are vastly different . in particular , the angle ( @xmath52 ) between the symmetry axis of the satellite ( @xmath53 ) and the instantaneous angular momentum vector ( @xmath54 ) can be expressed in terms of the three euler angles as @xmath55 in the early stages of the lageos mission when @xmath56 and @xmath57 this angle is rather small ( @xmath58 ) . a proper interpretation of the results of the numerical simulation requires a careful distinction between @xmath15 and @xmath59 ( where @xmath44 is the euler angle of the body frame ) . the two coincide only under the assumption that the @xmath18 component of the satellite s angular velocity is responsible for all of the satellite s energy , or , to put it differently , the angular momentum of the satellite is directed along the body axis of the satellite . as the satellite s spinning motion slows down , this last assumption is violated . @xmath15 represents only a part of @xmath59 , the other part being caused by the `` tidal locking '' effect . as we shall see , this is exactly what happens in the asymptotic phase of the satellite s motion . nevertheless , both @xmath15 and @xmath59 remain bounded . the spin dynamics are determined by euler s equations @xmath60 where @xmath61 , @xmath62 , @xmath18 are the components of the satellite s angular velocity in the body frame , @xmath23 , @xmath22 are the principal moments of inertia , and @xmath63 , @xmath64 , @xmath65 are the components of the torques along the satellite s principal axes . after substituting the expressions for @xmath61 , @xmath62 , @xmath18 in terms of the euler angles @xmath66 the euler equations become @xmath67 the torque components @xmath63 , @xmath64 , @xmath65 are due to gravitational and magnetic forces acting on the satellite @xmath68 gravitational torques in the body frame are given by @xmath69 using the standard dipole approximation , the gravitational potential @xmath70 is @xmath71 where @xmath72 is the direction cosine between ( 1 ) the radial vector from the satellite center of mass to the center of the earth , and ( 2 ) the symmetry axis of the satellite . it is related to euler s angles via @xmath73 where @xmath74 gives the angular position of the center of mass of the satellite in its orbit about the earth , and @xmath75 is an arbitrary starting position . the potential is given by @xmath76 and thus @xmath77 equations ( 10 ) and ( 14 ) lead to the following final expressions for the components of the gravitational torque in the body frame @xmath78 as for the magnetic effects , we are interested in the torque components acting on a conducting ball of radius @xmath79 spinning with angular velocity @xmath20 in an external magnetic field @xmath50 . we take our expressions from landau and lifshitz @xcite , noting that their results are for what we have dubbed the landau - lifshitz frame ( as described above ) , and for our purposes need to be transformed to the body frame . as already described , the landau - lifshitz frame is determined by the vectors @xmath20 and @xmath50 . if we introduce an arbitrary set of rectangular coordinates @xmath80 , @xmath81 , @xmath82 , in this frame @xmath20 and @xmath50 are represented as @xmath83 where hats ( @xmath84 ) denote vectors normalized to unity . the transition between this arbitrary frame and the landau - lifshitz frame is given by @xmath85_x\over \omega\vert\vec\omega\times\vec b \vert & [ ( \vec\omega \times\vec b ) \times \vec\omega ] _ y\over \omega \vert \vec\omega \times \vec b \vert & [ ( \vec\omega \times\vec b ) \times \vec\omega ] _ z\over \omega \vert \vec\omega \times \vec b \vert \\ ( \vec\omega \times \vec b)_x\over \vert\vec\omega \times \vec b\vert & ( \vec\omega \times \vec b)_y\over \vert\vec\omega \times \vec b\vert & ( \vec\omega \times \vec b)_z\over \vert\vec\omega \times \vec b\vert \\ \omega_x\over\omega & \omega_y\over\omega & \omega_z\over\omega \end{array}\right)\ , \left(\begin{array}{c}\hat x \\ \hat y \\ \hat z \end{array}\right ) , \label{17}\ ] ] where @xmath86 . the components of the magnetic torque in the landau - lifshitz frame are given by @xmath87 where @xmath88 is the volume of the ball , @xmath89 , @xmath90 , @xmath91 are components of the magnetic field in the landau - lifshitz frame , and the real and complex parts of the coefficient of magnetization are @xmath92 , \nonumber \\ \alpha '' & = & -{9 \delta^2\over 16 \pi a^2 } \left [ 1 - { a\over \delta } { { \rm sinh } \left ( 2 { a\over\delta}\right ) + \sin \left ( 2 { a\over\delta}\right ) \over { \rm cosh } \left ( 2 { a\over\delta}\right ) - \cos \left ( 2 { a\over\delta}\right ) } \right ] , \nonumber \label{19}\end{aligned}\ ] ] with @xmath93 here @xmath94 is the speed of light and @xmath95 is the specific conductivity of the material forming the ball . at small values of @xmath25 ( @xmath96 ) , @xmath97 and @xmath98 can be approximated by the expressions @xmath99 components of the magnetic field can be evaluated in the eci frame using the dipole approximation . in the spherical coordinate representation of the eci frame , the magnetic field components are @xmath100 where @xmath101 is the magnetic dipole moment of the earth . in the rectangular coordinate representation of the eci frame ( the index 1 is used everywhere for quantities in eci ) @xmath102 transforming these to the oci frame : @xmath103 where @xmath52 is the colatitude angle of the orbit with respect to magnetic north , and the index 2 is used for quantities in the oci . the satellite s semimajor axis is @xmath104 , and for the earth s magnetic dipole moment we used @xmath105 . although we do not average the magnetic field in our simulations , it was useful for back of the envelope calculations to note that the the magnetic field , averaged over one orbit , is @xmath106 , with components , @xmath107 the angles @xmath108 and @xmath109 are dependent upon the satellite s position in its orbit . the satellite s coordinates in the oci frame are @xmath110 where @xmath111 in eci we have @xmath112 hence , @xmath113 the three euler equations ( eq . [ 8 ] ) , with the magnetic and gravitational torques included ( properly transformed to the body frame ) , give us the vehicle to analyze qualitatively the spin dynamics of the lageos-1 satellite . we present our results from the numerical integration of these equations in the following two sections . we solved the euler equations ( eq . [ 8 ] ) using a fourth - order bulirsch - stoer algorithm with adaptive time - stepping @xcite . the equations were integrated for @xmath114 seconds , as we wanted to ( 1 ) reproduce the experimentally - measured spin rates ( @xmath115 following launch ) , ( 2 ) examine the spin - orbit resonance ( @xmath116 after launch ) , and ( 3 ) reveal the asymptotics of the spin dynamics ( @xmath117 after launch ) . the experimentally - measured exponential decrease in the spin rate imposed a constraint on our theoretical model , linking the `` effective '' radius of the satellite ( @xmath79 ) with the satellite s `` effective '' conductivity ( @xmath95 ) : @xmath118 the satellite was modeled as a @xmath119 radius spheroid of brass ( @xmath120 ) . lageos i s moment of inertia about the body axis is @xmath121 , while the moment of inertia perpendicular to the body axis is @xmath122 , corresponding to an approximately @xmath123 deviation from sphericity . from the experimental data , we observed a deviation from pure exponential damping of the spin of the satellite at early times . this is presumably due to the satellite s transition from magnetic opaqueness to transparency in the course of its spin damping . a rapidly rotating conductor , with angular velocity @xmath25 and conductivity @xmath95 , will have an associated magnetic skin depth @xmath124 this skin depth starts out considerably smaller than the satellite , but as the satellite s spin is damped down , the skin depth becomes much larger than the satellite s diameter . although this transition effect will be more pronounced for our idealized spherical brass model satellite than for lageos ( with its additional surface structure ) , it helps account for the structure in the experimental spin - down data ( for which it would have been convenient to have access to the associated error bars ) . it is for this reason that we began our calculations within the transparent phase , at @xmath125 . we integrated forward in time to @xmath126 , and backwards to @xmath127 . at @xmath128 , the skin depth of our satellite model , given the experimentally measured spin rate of @xmath129 and a conductivity for brass ( @xmath130 ) , is @xmath131 . we started the integration with the satellite in a retrograde circular orbit , at a radius of @xmath132 and an inclination of @xmath133 . at @xmath128 , the satellite was located over the equator and positioned along the @xmath134 axis ( @xmath135 ) . we inserted the body axis of the satellite into the orbital plane with the angular momentum vector parallel to the oci @xmath136-axis . the initial spin of the satellite was determined by the experimental measurements , and was set to @xmath137 . the initial conditions were @xmath138 in running this initial data backward in time from @xmath139 to launch at @xmath140 , we recovered the following angles and angular velocities ( measured in @xmath141 ) : @xmath142 the magnetic field in our simulation was assumed to be a perfect dipole field , of moment @xmath143 and aligned along the @xmath37-axis of the eci frame . we have identified three distinct phases in the spin dynamics of the lageos satellite , which we shall refer to as ( 1 ) the fast spin phase , ( 2 ) the spin - orbit resonance phase , and ( 3 ) the asymptotic phase . \a ) _ fast spin phase_. this first phase , from @xmath140 to @xmath144 , is characterized by an exponential decrease in the spin rate ( @xmath145 ) of the satellite ( fig . [ figure3 ] ) from @xmath146 to @xmath147 . the body axis of the satellite is aligned with the angular momentum of the satellite in this phase ; hence , all other quantities ( angular momentum , kinetic energy , _ etc . _ ) also decrease exponentially . the nutation of the satellite ( the angle between the body axis of the satellite and the normal to the orbital plane ) undergoes a steady increase from @xmath148 at @xmath149 to @xmath150 over a period of @xmath151 , indicating a nutation angular velocity of @xmath152 . the nutation then settles down to a `` pseudo - stable '' state at @xmath153 over the next @xmath154 years and remains at this value ( @xmath155 ) until the onset of the spin - orbit resonance at @xmath156 ( fig . [ figure6 ] ) . finally , within this twenty five year period the satellite precesses in a positive sense by 63 revolutions before unwinding when entering the spin - orbit resonance phase . \b ) _ spin - orbit resonance phase_. the spin dynamics abruptly change at @xmath157 . this is precisely when the satellite s spin , decreased by magnetic damping , approaches the orbital angular velocity @xmath158 the conductivity of the satelite was chosen to reproduce experimentally observed exponential decay in the spin rate of the satellite , @xmath159 with ( @xmath160 time constant ) . therefore , the spin - orbit resonance should occur at @xmath161 , which is in agreement with the numerical results . the resonance phase is marked by a movement of the angular momentum vector to a position orthogonal to the orbital plane , and is furthermore characterized by the beginning of satellite wobble ( _ i.e. _ , the point in time when @xmath52 of eq . ( [ * ] ) becomes nonzero and the body axis becomes misaligned with the instantaneous angular momentum vector ) . from this point forward it is more illustrative to examine the dynamics of the instantaneous angular velocity and momentum rather than the euler angles . in addition to the dramatic changes in the spin dynamics , this second phase also gives rise to a reversal in the signs of the precessional velocity ( @xmath162 ) and spin ( @xmath163 ) . \c ) _ the asymptotic phase_. following the spin - orbit resonance phase , the spin dynamics gradually settled down to an asymptotic regime over the course of @xmath164 . not surprisingly , the satellite becomes tidally locked ( think of the moon ) . in particular , the asymptotic value of the total angular velocity is equal to the orbital angular velocity , subject to small fluctuations . we note that in this phase the torques induced from the changing magnetic field due to _ orbital _ motion of the satellite will become important , and should no longer be ignored . however , their addition will not significantly change dynamics , as the energies at this point are quite low . from our numerical runs , a rough estimate of the asymptotic behavior of the satelite model ( modulo phase and a finite offset in @xmath44 ) is given by @xmath165 the asymptotic values of the other relevant parameters ( fig . [ figure4 ] ) : @xmath166 = = = of the five largest sources of error identified in the lageos-3 experiment , the earth and solar - induced surface forces are potentially the most troublesome ( table [ table1 ] ) . the anisotropic heating of the satellite , and subsequent reradiation , gives a `` thermal rocketing '' perturbation ( referred to as the rubincam effect or the yarkowsky thermal drag ) which tends to degrade the experiment . to model this effect requires , in part , a detailed knowledge of the behavior of the angular momentum of the satellite . toward this end we have derived , and solved numerically , a simplified set of euler equations that evolve the angular momentum vector for a slightly oblate spheroid of brass orbiting an earth - like mass , idealized as being a perfect sphere and having a perfect polar - oriented dipole magnetic field . the euler equations included both the tidal gravitational torques and the eddy - current torques , as well as the resistive damping torques , as modeled by complex magnetization coefficients . using this rather simplified model , we have identified three phases of the rotational dynamics a fast spin phase , a spin - orbit resonance phase , and an asymptotic phase ( fig . [ figure3 ] ) . we have also identified an error in the previously established model of asymptotic spin dynamics @xcite . this error has led to confusion and , in attempts to reconcile observed data with theoretical predictions , has led others to hypothesize erroneous models for the moments of inertia of lageos-1 @xcite . our results have led us to formulate four as yet unresolved questions : ( 1 ) can we obtain the asymptotic solution analytically , and in so doing can we understand the wobbling or slippage of the euler angles with respect to the relatively stable total instantaneous angular velocity ? ; ( 2 ) can we understand why the _ rms _ fluctuations in the gravitational potential energy cause the asymptotic value of the angular momentum vector to be offset from the orbital plane by @xmath167 ? ; ( 3 ) can we understand why the nutation angle ( @xmath19 ) drifts initially at a rate of @xmath168 and reaches a pseudo - stable value of @xmath169 ? ; and ( 4 ) can we understand the fluctuations in the spin rate ( @xmath145 ) over the first @xmath170 , which do not appear to have been detected experimentally ? we are addressing these questions by ( 1 ) introducing a more realistic model of the satellite and earth into our calculations @xcite , and ( 2 ) exploring more of phase space by way of poincare sections . the results presented here provide us with clues that must be pieced together to reveal the physics behind the complex motion we observe . the current spin dynamics model suggests that we launch lageos-3 , with as large a spin @xmath171 as possible , into an obliquity of @xmath172 ; although , due to the qualitative nature of our results , the precise numbers are far from being conclusive . we are currently working with the center for space research at the university of texas at austin to determine the impact this revised model of the spin dynamics of lageos will have on the lageos-3 mission ( in particular , how will the rubincam effect alter the line of nodes of the orbital plane ? ) . in addition , we are working closely with colleagues at the university of texas and the university of maryland to reconcile the experimental measurements of the spin dynamics of lageos-1 with our theoretical model @xcite . furthermore , we will propose an optimal experimental measurement schedule in support of the proposed lageos-3 mission . we wish to thank stirling colgate , douglas currie , christopher fuchs , and sara matzner for many helpful discussions . this work was supported in part by a grant from los alamos national laboratory under ldrd xl31 , by the afosr under the summer faculty research program , and by nsf grants phy 88 - 06567 and phy 93 - 10083 . 99 j. m. bardeen and j. a. peterson , _ app . j. lett . _ * 195 * , l65 ( 1975 ) ; d. a. macdonald , k. s. thorne , r. h. price and xiao - he zhang , _ astrophysical applications of black hole electrodynamics _ in _ black holes : the membrane paradigm _ , edited by k. s. thorne , r. h. price , and d. a. macdonald ( yale university press , new haven , 1986 ) , ch . h. thirring and j. lense , _ phys . z. _ * 19 * , 156 ( 1918 ) ; h. thirring , _ ibid _ * 19 * , 33 ( 1918 ) , _ ibid _ * 22 * , 29 ( 1921 ) . an english translation is given by b. mashhoon , f. w. hehl , and d. s. theiss , _ gen . . gravit . _ * 16 * , 711 ( 1984 ) . c. w. f. everitt , in _ experimental gravitation _ , edited by b. bertotti ( academic , new york , 1973 ) ; r. a. vanpatten and c. w. f. everitt , _ phys . * 36 * ( 1976 ) . i. ciufolini _ phys . * 56 * , 278 ( 1986 ) . j. ries , private communication ( 1993 ) . d. p. rubincam , _ j. geophys research _ * 92 * , 1278 - 1294 ( 1987 ) ; _ ibid _ * 93 * , 13805 ( 1988 ) ; _ ibid _ * 95 * , 4881 ( 1990 ) ; _ the lageos along track acceleration : a review _ , paper presented at the first william fairbanks meeting on relativistic gravity experiments in space , rome , italy , september 10 - 14 , 1990 . b. bertotti b. and l. iess , _ j. geophys . research _ * 96 * , 2431 ( 1991 ) . j. p. vinti , _ theory of the spin of a conducting satellite in the magnetic field of the earth _ , defense technical information center , brl-1020 ( 1957 ) . h. goldstein , _ classical mechanics _ ( addison - wesley , reading , ma , 1981 ) . c. fuchs , _ lagrangian formulation of lageos s spin dynamics _ , final report , 1992 air force summer research program , august 1992 . c. w. johnson , c. a. lundquist , and j. l. zurasky , _ the lageos satellite _ , paper presented at the international astronautical federation xxvii congress , anaheim , ca , october 10 - 16 , 1976 ) . l. d. landau and e. m. lifshitz , _ electrodynamics of continuous media _ ( pergamon press , oxford , 1984 ) . w. h. press , s. a. teukolsky , w. t. vetterling , and b. p. flannery , _ numerical recipes in c _ ( cambridge university press , cambridge , 1992 ) . r. scharroo , k. f. wakker , b. a. c. ambrosius , and r. noomen , _ j. geophys . research _ * 96 * , 729 ( 1991 ) . r. p. halverson and h. cohen , _ ieee trans . _ ane-11 , 118 ( 1964 ) . d. currie , s. habib , r. matzner , and w. a. miller , ( in preparation ) .

lageos is an accurately - tracked , dense spherical satellite covered with 426 retroreflectors . the tracking accuracy is such as to yield a medium term ( years to decades ) inertial reference frame determined via relatively inexpensive observations . this frame is used as an adjunct to the more difficult and data intensive vlbi absolute frame measurements . there is a substantial secular precession of the satellite s line of nodes consistent with the classical , newtonian precession due to the non - sphericity of the earth . ciufolini has suggested the launch of an identical satellite ( lageos-3 ) into an orbit supplementary to that of lageos-1 : lageos-3 would then experience an equal and opposite classical precession to that of lageos-1 . besides providing a more accurate real - time measurement of the earth s length of day and polar wobble , this paired - satellite experiment would provide the first direct measurement of the general relativistic frame - dragging effect . of the five dominant error sources in this experiment , the largest one involves surface forces on the satellite , and their consequent impact on the orbital nodal precession . the surface forces are a function of the spin dynamics of the satellite . consequently , we undertake here a theoretical effort to model the spin ndynamics of lageos . in this paper we present our preliminary results .

epithelial ovarian cancer ( eoc ) is the fourth leading cause of cancer - related deaths in women in the united states and the leading cause of gynecologic cancer deaths with a 5-year survival of only 3040% [ 15 ] . most patients are diagnosed with advanced - stage disease and the majority recurs despite optimal surgical debulking and initial response to chemotherapy . recurrence is almost always accompanied by the development of chemoresistance and carcinomatosis , which may not be amenable to surgery . current studies suggest that the tumor is initiated and maintained by a unique population of cells with stem - like properties . the cancer stem cell ( csc ) hypothesis implies that the inherently chemoresistant csc can persist after chemotherapy and repopulate the tumor leading to recurrence [ 710 ] . contrary to the stochastic model of cancer ( clonal expansion ) , the cancer stem cell model holds that tumors are hierarchically organized and only some cells have the capacity to indefinitely self - renew and sustain tumor growth [ 11 , 12 ] . it is thought that cscs are able to survive conventional chemotherapies , which usually target fast dividing cells , and give rise to recurrent tumors that are more resistant and more aggressive . thus , detection of the csc population has implications for the diagnosis and treatment of most cancers . one of the major problems in elucidating the cellular origin and pathogenesis of ovarian cancer is that it is a heterogeneous disease . indeed , ovarian cancer can be classified into multiple types ( serous , endometrioid , clear cell , and mucinous ) , with each type having widely different clinicopathologic properties . it is therefore possible that each of these types of ovarian cancer has different cellular origin . it is therefore not surprising that stem cell properties have been reported in ovarian cancer cells isolated using different cell surface markers , including cd44 , cd133 , or cd24 [ 1421 ] . each of these ovarian cancer cell types may represent either a hierarchy of csc or an entirely different population of csc for that particular ovarian histotype . recently we , and others , demonstrated the presence of epithelial ovarian cancer stem cells ( eoc stem cells ) in tissue samples and cell lines [ 1619 , 22 ] . several markers have been used for the identification of eoc stem cells , which reflect the heterogeneity of ovarian cancer . these markers include cd44 , cd133 , cd24 , aldh1 , myd88 , and cd117 . of these markers , the cell surface protein cd44 has been most extensively described to potently enrich the eoc stem cells . cd44 + eoc stem cells express pluripotency markers such as -catenin , oct-4 , and ssea-4 and have been demonstrated to be the chemoresistant progenitors in vivo and are able to differentiate into the heterogenous cell types comprising the tumor [ 14 , 22 ] . the objectives of the present study were twofold : ( i ) to characterize the location of cd44 + eoc stem cells in tissue samples and ( ii ) to determine whether the cd44 + eoc stem cell load correlates with clinical parameters in ovarian cancer patients . using ovarian cancer tissue sections from 117 patients with primary disease , we investigated the relationship between the number of cd44 + eoc stem cells and various clinical parameters , which include chemoresponse and progression - free survival . the experiments described here were performed using five eoc stem cells ( cd44 + ) and five mature ovarian cancer cells ( meoc cells , cd44 ) that our laboratory isolated and established from either ascites or ovarian tumors . meoc cells correspond to the cd44 component of the tumor or from cells derived from cd44 + eoc cells following in vitro and in vivo differentiation . we found the same characteristics in cd44 cells isolated from the original tumor or cd44 cells originated from cd44 + eoc cells following in vitro and in vivo differentiation . we generated fluorescence - labeled eoc stem cell clones by stable transfection with lentiviral constructs expressing the red fluorescence protein tomato under the ubiquitin promoter - driven l2 g ( pfu - l2 t ) as described elsewhere . briefly , cell pellets were lysed on ice in 1 phosphate - buffered saline with 1% np40 , 0.1% sds and freshly added 20 ml / ml protease inhibitor cocktail ( sigma chemical , st louis , mo , usa ) and 2 mm phenylmethylsulfonyl fluoride ( sigma chemical ) . protein concentration was determined by bca protein assay ( pierce biotechnology , rockford , il , usa ) , and proteins were stored at 80c until further use . a quantity of 20 g of each protein sample was denatured in sample buffer and subjected to 12% sds - polyacrylamide gel electrophoresis ( page ) as previously described . the following antibody dilutions were used : cd44 antibody ( 1 : 2000 ) mem-263 ( novus biologicals , littleton , co , usa ) , monoclonal ck18 antibody dc10 ( 1 : 1000 ) ( cell signaling , danvers , ma , usa ) , and rabbit anti - human -actin ( 1 : 10,000 ) . briefly , cells were trypsinized and pelleted cells were incubated with either pe - anti ck18 or apc - anti cd44 antibodies ( ebioscience , san diego , ca ) . data was acquired using bd facs calibur and analyzed using cell quest pro ( bd bioscience ) . tumor tissue and patients ' clinical data were collected from a prospective translational research protocol . the patients were all newly diagnosed with ovarian cancer and referred for first - line platinum - based chemotherapy at the departments of clinical oncology at vejle , aalborg , odense , and herning hospitals . collected data were entered into case report forms and all tumor specimens underwent central pathology evaluation . patients received both oral and written study - related information before they signed a consent form prior to collection of biological material . the danish biomedical research ethics committee and the danish data protection agency approved the study . a majority of the patients underwent primary debulking surgery , while a minor portion ( n = 3 , 2.6% ) were treated with neoadjuvant chemotherapy . all the patients in this cohort received first - line combination chemotherapy with carboplatin ( auc5 ) and paclitaxel ( 175 mg / m ) . response to chemotherapy was assessed according to gcig ca125 criteria [ 26 , 27 ] and/or recist criteria by ct or mri scans . formalin - fixed , paraffin - embedded tissue blocks obtained during primary tumor debulking and prior to first - line chemotherapy were used for immunohistochemical staining for cd44 or ck18 ( cell signaling ) 1 : 100 dilution . the slides from the primary debulking operations were collected from nine regional danish departments of pathology and underwent central pathology revision ( mw ) . the tumors were classified according to the who histological classification and graded according to shimizu et al . . one representative paraffin - embedded formalin - fixed tumor block from each patient was selected and 4 m sections were cut and stored at 80c until further analysis . one section from each patient was used for ihc with monoclonal cd44 antibody ( 1 : 2000 ) mem-263 ( novus biologicals , littleton , co , usa ) and monoclonal ck18 antibody dc10 ( 1 : 1000 ) ( cell signaling , danvers , ma , usa ) . in brief , the sections were deparaffinized in tissue clear ( tissue tec , sakura finetek , zoeterwoude , netherlands ) followed by washes in a graded series of ethanol for rehydration in tissue tec prism ( sakura , prohosp , vaerloese , denmark ) . heat - induced epitope retrieval was done in a microwave oven using teg ph 9.0 with 15 minutes boiling and 15 minutes for cooling down . the sections were incubated with the primary antibody in 1% bovine serum albumin / tris - buffered saline for 30 minutes at room temperature . immunohistochemical staining was performed by the autostainer plus link ( as 10030 dako , glostrup , denmark ) according to manufacturer 's instruction . dako envision+ ( dako , glostrup , denmark ) was used for antibody detection and was followed by visualization with dab+ ( dako , glostrup , denmark ) . after washing , the reaction was enhanced by 0.5% copper sulphate in tbs for 10 minutes , and the slides were counterstained with mayers sour hematoxyline before dehydration and mounting . to validate the immunohistochemical procedure , negative and positive controls a small tissue microarray containing ovarian tumors was used together with tissue from appendix and tonsil for positive controls . the same tissue was incubated in 1% bovine serum albumin / tris - buffered saline but without the primary antibody for negative control . the study pathologist ( mw ) scored all the samples : the whole tumor slide was evaluated , and the percentage of cd44 positive stained cells was divided into 0% , > 05% , > 5%10% , > 10%20% , > 20%50% , and > 50% . for classification , we divided the patients into those with < 20% cd44 + cells and those with > 20% cd44 + cells . the correlation between cd44 expression and clinicopathological parameters was assessed by statistics and the same applied to the association between cd44 expression and response to chemotherapy . progression - free survival was defined as the elapsed time from date of diagnosis ( date of primary surgery ) until progression or death attributable to any cause . univariate progression - free survival analysis was performed using the kaplan - meier estimates and log - rank statistics for comparison of survival plots . the parameters entered in the cox analysis were cd44 status ( low expression : < 20% positive cells ; high expression : > 20% positive cells ) , figo stage , grade , and residual tumor as categorical variables , and age at diagnosis as a continuous variable . statistical analyses were performed with the ncss software ( version 2007 , kaysville , utah , http://www.ncss.com/ ) . we previously demonstrated that the ovarian cancer stem cells are cd44 + , represent the chemoresistant population , and are able to differentiate in vitro and in vivo to cd44 cells . as shown in figure 1 , cd44 + , but not cd44 , eoc cells express high levels of aldh1 , further confirming that the cd44 + eoc stem cells express the majority of identified markers for tumor initiating cells ( figure 1 ) [ 15 , 21 ] . to closely monitor the process of differentiation , we labeled pure clones of cd44 + eoc cells with a fluorescent reporter , which allows flow cytometry analysis and in vivo imaging . thus , cd44 + eoc stem cell clones were stably transfected with a viral vector expressing the red fluorescence protein cd44+/tomato+ eoc cells were injected into nude mice , and the established tumor ( 60 days later ) was evaluated for cd44 and tomato . as shown in figure 2 , prior to injection the eoc stem cells are 99.5% cd44+/tomato+ . these results demonstrate that the cd44 cells originated from the cd44+/tomato+ eoc cells ( figure 2 ) . we previously showed , using gene expression microarray , that ck18 expression is 7-fold higher ( p = 0.0007 ) in cd44+/myd88 + eoc stem cells compared to the cd44/myd88 mature ovarian cancer stem cells ( moccs ) . to validate this finding , we determined the levels of ck18 in five eoc stem cell clones , three mocc clones , and in the eoc cell line a2780 using western blot analysis . as shown in figure 3 , ck18 expression is limited to the eoc stem cells and not the moccs . correlation between cd44 and ck18 expression was also observed by flow cytometry and western blot ( figures 3(a ) , 3(b ) ) . evaluation of the location of cd44 + and ck18 + cells in tumor tissues obtained from ovarian cancer patients showed that cd44 + ( figures 3(c ) , 3(d ) ) and ck18 + cells ( figures 3(e ) , 3(f ) ) are surrounded by cd44-/ck18 moccs . within tumor nests , single ( figure 4(a ) ) and clusters ( figures 4(b)4(d ) ) of ck18 + cancer cells were observed . these cells morphologically appear less differentiated with larger size , higher nuclear to cytoplasm ( n / c ) ratio , more prominent nucleoli , and a vesicular chromatin pattern ( figure 5 ) . in cells with a more differentiated phenotype ( smaller size and lower n / c ratio ) , ck18 staining was weak to absent ( figures 3 and 4 ) . some of the ck18 + clusters were observed in close proximity to the stroma and showed a clear and defined basal membrane ( figure 5 ) . the observed distribution of the ck18 + cancer cells follows the description of the niche associated with csc [ 9 , 29 ] . our next objective was to determine whether the prevalence of eoc stem cells has a prognostic value . for this study , we focused using a single marker and selected cd44 as a widely accepted marker for the identification of ovarian cancer stem cells . thus , we analyzed cd44 staining in ovarian cancer tissue sections obtained from 117 patients . the clinical - pathological data of the study cohort is presented in table 1 . the majority of the patients were older than 50 years with histopathologic diagnosis of serous ovarian cancer . in addition , most of the patients were classified figo stage ii and higher , with moderate or poorly differentiated tumors ( grade > 1 ) ( table 1 ) . however , we observed variability in the number , distribution , and location of cd44 + cancer cells amongst patients . of all patients tested , 39 patients had between 15% cd44 + cancer cells , 38 patients had > 510% cd44 + cells , 19 patients had > 1020% cd44 + cells , 9 patients had > 2050% cd44 + cells , and 11 patients had > 50% cd44 + cells . , we classified the samples as low expression of eoc stem cells if they had less than 20% positive cells ( < 20% eoc stem cells ) and high expression if the sample had more than 20% positive cells ( > 20% eoc stem cells ) . thus , of the 117 patients , 20 patients were considered high expression and 97 patients were considered low expression ( table 1 ) . patients with figo stage i tumors had a higher number of cd44 + eoc stem cells ( > 20% cd44 + cells ) with 57.1% of the stage i patients expressing > 20% cd44 + cells . for figo stages ii , iii , and iv , 18.2% , 12.9% , and 4.5% expressed > 20% cd44 + cells ( table 1 ) . thus , a significant percent had figo stage i ( p = 0.00025 ; x = 19.2 ) . similarly , the majority of patients with grade i tumors showed high expression of eoc stem cells ( > 20% cd44 + cells ) ( p = 0.021 , x = 7.7 , table 1 ) . high expression of cd44 + eoc cells was seen in fifty percent , 14.3% , and 12.1% of grade 1 , 2 , and 3 disease , respectively . this indicates that in patients with primary disease , tumors tend to have a lower number of cd44 + eoc stem cells as the disease progresses . we then evaluated whether a correlation exists between percentage of cd44 + eoc stem cells and response to treatment . the 14 patients with figo stage i cancer comprised 2 patients with stage ia cancer ( one clear cell cancer and one grade 2 serous = patients with adverse histological features / high risk patients that routinely receive chemotherapy ) and 12 patients with stage ic tumors that according to guidelines are treated with adjuvant chemotherapy . although it was only marginally statistically significant , we observed an obvious trend ( p = 0.06 ) for poorer response rates among patients with > 20% cd44 + eoc stem cells . only 73% of these patients had complete or partial response compared to 90% in patients with low number of eoc stem cells ( < 20% cd44 positive cells ) . similarly , 27% of patients with > 20% positive cells for cd44 had stable or progressive disease during or by the end of first line carboplatin and paclitaxel treatment compared to only 10% in the patients with a low number of cd44 + cells ( < 20% cd44 + eoc stem cells ) ( table 2 ) . although a majority of patients with early - stage ovarian cancer respond to treatment and have a good prognosis , 10% of these patients will recur in spite of appropriate debulking and chemotherapy . thus , in order to determine whether there is a correlation between the presence of eoc stem cells and recurrence , we analyzed our study population with respect to progression - free survival . in multivariate analysis , the percentage of cd44 + eoc stem cells was independently correlated to progression - free survival with a hazard ratio of 2.44 ( 1.085.52 ) 95% ci , toward shorter survival for patients with high number of eoc stem cells ( table 3 ) . as anticipated , figo stage and residual tumor were also independently correlated to progression - free survival . further subgroup analysis showed that in early - stage ovarian cancer ( figo stage i / ii ) , patients with high number of cd44 + eoc stem cells ( > 20% ) had significantly shorter progression - free survival compared to patients with a low number of cd44 + cells eoc stem cells ( < 20% ) ( p = 0.026 ) ( figure 6 ) . in contrast , in patients with advanced - stage ovarian cancer ( figo stage iii / iv ) , the number of cd44 + eoc stem cells did not correlate with progression - free survival ( p = 0.95 , data not shown ) . we show in this paper that cd44 + eoc stem cells can be detected in tumor sections obtained from patients with ovarian cancer . interestingly , in this retrospective study , we found that there was an inverse correlation between figo stage / disease grade and the presence of these cells . however , our findings show that in early - stage ovarian cancer , patients with tumors containing > 20% cd44 + eoc stem cells had a shorter progression - free survival compared to patients with tumors having < 20% of these cells . in multivariate analysis , we found that cd44 positivity was an independent predictor of poor progression - free survival . since high levels of cd44 + eoc stem cells correlated with poor prognosis in early stage ovarian cancer but not in patients with advanced figo stage , it is possible that the high level of eoc stem cells in stage i , and ii resulted in the observed significance in the multivariate analysis . the existence of csc has been demonstrated in several tumor types such as acute myelogenous leukemia , breast , pancreatic , and brain tumors [ 11 , 3033 ] . these cells are believed to sustain tumor formation through their self - renewal and differentiation potential . in ovarian cancer , bapat et al . reported the isolation and identification of ovarian csc . using an in vitro model system comprised of 19 spontaneously immortalized clones derived from an advanced - grade patient , the authors demonstrated the ability of 2 clones to form spheroids and recapitulate the human tumor in nude mice . these cells were shown to express cd44 , e - cadherin , and the stem cell factors nestin , nanong , and oct-4 . in a separate study , zhang et al . reported the tumor - initiating capacity of cd44+/cd117 + ovarian cancer cells in mice . the identification of csc is done based on the presence of extracellular markers that are thought to be stem cell specific . some of the most commonly identified markers are cd133 , cd44 , and cd24 , which are found in breast , prostate , pancreas , and ovarian cancer . although these markers are thought to be indicative of csc phenotype , it is not clear whether they are universal markers and if it is a characteristic of csc derived from all type of tumors . that is the case for ovarian cancer where multiple markers have been described for the isolated tumor initiating cells . a potential explanation for the discrepancy could be due to studies using cancer cells lines which may not represent the original tumor . however , it may also be a result of the heterogeneous nature of ovarian cancer and its multiple sources of origin [ 34 , 35 ] . an ovarian cancer stem cell originated in the fallopian tube might present different surface markers than a csc originated from the endometrium or the surface epithelium of the ovaries . our group previously identified at least two types of eoc cells based on their response to chemotherapy : type i - chemoresistant and type ii - chemosensitive eoc cells [ 36 , 37 ] . further characterization showed that these cells have additional differences in terms of growth , cytokine production , and intracellular markers . while type ii eoc cells represent the classical ovarian cancer cells characterized by fast growth and lack of cell to cell contact inhibition , type i eoc cells are characterized by slower growth , which is inhibited upon cell to cell contact . in addition , type i , but not type ii , eoc cells have constitutive nf - kb activity and constitutively secrete il6 , il8 , mcp-1 , and gro . gene expression microarray analysis comparing these two types of cells further showed that type i eoc cells expressed significantly higher levels of the stem cell markers , cd44 and ssea-4 , the tlr adapter protein myd88 , cytokeratin 18 , trop-1 , and others . these findings suggest that type i eoc cells may represent the population that has stem - like properties . indeed , we demonstrated that type i eoc cells , as selected by cd44 , are able to form xenografts in mice and resulted in tumors containing both cd44 + and cd44 cells . in this study , we evaluated additional markers present in our recently isolated cd44 + eoc cells . we observed that these cells are also ck18 + , a marker associated with epithelium of the fallopian tubes . aldehyde dehydrogenase ( aldh1 ) has been proven useful for the identification of cancer stem cells , including ovarian cancer ; therefore , we evaluated the expression of aldh1 in the identified cd44 + eoc stem cell clones . we found high levels of aldh on eoc stem cells by immunofluorescence , suggesting that aldh1 could be used also as a marker to monitor the presence of cancer stem cells . we described additional evidence in support of previous findings showing that type i eoc cells ( cd44 + ) are the source of type ii cells or cd44. to closely monitor eoc stem cell fate and function in mice , we labeled cd44 + cells with dual - function reporter genes encoding the sequence of the florescence protein tomato ( red color ) . using a xenograft tumor model , we demonstrated that following injection of double positive cd44+/tomato+ cells , the newly formed tumor originating from these double positive cells is characterized by cd44 cells , which maintain the expression of the fluorescent protein tomato . this demonstrates that cd44 + eoc stem cells can both self - renew and differentiate . moreover , microscopic analysis of the xenografts showed that cd44 + eoc cells were able to recapitulate the morphology of the original tumor . finally , in vitro differentiation of the chemoresistant cd44 + eoc stem cells resulted in chemosensitive cultures that have lost cd44 . in this study , we showed that the presence of cd44 + eoc stem cells correlates with poor prognosis . since the cd44 + cells are in general more chemoresistant , they can persist after chemotherapy and may initiate recurrence upon the completion of treatment . we found eoc stem cells localized in clusters surrounded by differentiated ovarian cancer cells and in close proximity with the stroma . emerging evidence indicates that a specialized environment , the stem cell niche , is one of the factors regulating stem cell maintenance and self - renewal [ 9 , 40 , 41 ] . this is illustrated by the studies of yauch et al . who showed that inhibition of hh pathway in pancreatic associated stroma cells resulted in suppression of tumor growth . in contrast , inhibition of the same pathway in the cancer cells did not have any effect on tumor growth . this suggests that the variation on the number of cancer stem cells observed in our study may be the result of alteration in the interaction between the stroma and the cancer stem cells . a functional stroma might maintain a small pool of cancer stem cells while promoting differentiation . however , disruption of the stroma - cancer stem cells interaction might lead to uncontrolled self - renewal and significant increase in the pool of chemoresistant eoc stem cells and consequent poor prognosis . several studies have evaluated cd44 expression in ovarian cancer tumors and correlated with survival outcome . cd44 expression has been reported to correlate with a significantly shorter disease survival than for patients with cd44 negative tumors [ 44 , 45 ] . however , studies investigating cd44 expression in terms of ihc and survival are contradictory [ 46 , 47 ] . differences between these studies that could account for differences in their findings could be attributed to technical factors , including the use of different monoclonal or polyclonal antibodies that exhibit variable efficacy in paraffin - embedded tissues and to different methods used for assessment of immunostaining . in this study , we focused on cd44 expression as a marker of the cancer stem cells and its evaluation is based on the percentage of ovarian cancer stem cells present in the tumor . cd44 is more than a marker ; this transmembrane receptor has been shown to be important in various cellular processes such as growth , differentiation , and motility . the most studied function of cd44 is its role as the receptor for hyaluronan ( ha ) . binding of ha to cd44 controls cell - cell interactions , as well as interactions of the cell with the extra - cellular matrix . furthermore , it can function as detector of tissue damage and promote tissue repair . therefore , it is possible that cd44 expression in eoc stem cells might play a central role in self - renewal and the response to tissue damage . we show their existence as clusters located close to the stroma forming what has been described as the csc niche . furthermore , we demonstrate a correlation between the percentage of cd44 + eoc stem cells and survival in early - stage ovarian cancer . although it is a small cohort , especially the early stage , the findings from this study are important since they suggest that quantification of the number of eoc stem cells present in the tumor can be used as a predictor of disease and could be applied for treatment selection in early - stage ovarian cancer .

epithelial ovarian cancer stem cells ( eoc stem cells ) have been associated with recurrence and chemoresistance . cd44 and ck18 are highly expressed in cancer stem cells and function as tools for their identification and characterization . we investigated the association between the number of cd44 + eoc stem cells in ovarian cancer tumors and progression - free survival . eoc stem cells exist as clusters located close to the stroma forming the cancer stem cell niche . 17.1% of the samples reveled high number of cd44 + eoc stem cells ( > 20% positive cells ) . in addition , the number of cd44 + eoc stem cells was significantly higher in patients with early - stage ovarian cancer ( figo i / ii ) , and it was associated with shorter progression - free survival ( p = 0.026 ) . this study suggests that quantification of the number of eoc stem cells in the tumor can be used as a predictor of disease and could be applied for treatment selection in early - stage ovarian cancer .

human leukocyte antigen - g ( hla - g ) is a natural molecule involved in the establishment and maintenance of maternal tolerance to semiallogeneic fetal tissues [ 16 ] . decreased expression of hla - g during pregnancy has been noted as a contributing factor to preeclampsia and multiple miscarriages [ 711 ] . in addition , hla - g expression has been identified in pancreas , adult thymic cells , and stem cells , as well as in pathological conditions including cancer , transplantation , hiv infection , and inflammatory diseases [ 1227 ] . hla - g binds to several receptors , including ilt2 , ilt4 , and kir2dl4 receptors , to inhibit immune responses of myelomonocytic cells , dendritic cells , t cells , b cells , and nk cells [ 5 , 2835 ] . in addition to membrane - bound forms ( hla - g1 , -g2 , -g3 , and -g4 ) , hla - g is also presented by several soluble isoforms ( shla - g1 , -g5 , -g6 , and -g7 ) generated through two mechanisms : alternative splicing and proteolytic release , which is known to be mediated by metalloproteases [ 36 , 37 ] . significantly high levels of shla - g were determined in several physiological and pathological conditions , including an association with higher pregnancy and implantation rates . it has been determined that a high level of shla - g is correlated with clinical manifestation of several diseases , rheumatoid arthritis , systemic lupus erythematosus , asthma , and hiv infection . increased levels of shla - g were correlated with disease progression in patients with hematological malignancies and solid tumors , including patients with acute leukemia , lymphoma , chronic lymphatic leukemia , melanoma , breast cancer , glioma , and renal and lung carcinomas [ 25 , 38 ] . recent studies showed that shla - g molecules are involved in prolongation of allograft survival in patients with organ / tissue transplantation [ 3941 ] . in most studies plasma / serum levels of hla - g was determined by elisa . however , hla - g - specific elisa has limitations and does not discriminate the presence of monomer or dimer isoforms of hla - g . new data has revealed that disulfide - linked dimeric complexes of hla - g have high preferential binding to immune inhibitory receptors , induce efficient immune inhibitory receptor signaling , and have strong functional activities [ 32 , 4245 ] . limited data are available on the role of hla - g dimers in clinical pathological conditions . the outstanding questions are whether these hla - g dimers are formed in patients with organ transplantation and what their function might be in the prolongation of allograft survival . here first , we determined that the levels of shla - g dimers were significantly higher in patients with no rejection episode compared with patients that have a chronic rejection of a kidney transplant . the high levels of shla - g dimers were associated also with increased expression of the membrane - bound form of hla - g on monocytes from patients that have no rejection episode of kidney transplant . hla - g also has the ability to reduce inflammatory responses through the inhibition of immune cells to produce proinflammatory molecules . increased expression of mmps was observed in several human diseases , including cancer and autoimmune diseases , suggesting an involvement of these enzymes in immunity , inflammatory responses , and repair mechanisms . mmp-9 and mmp-2 are especially able to modulate inflammatory responses via cytokine / chemokine actions . here we demonstrated that the high levels of shla - g dimers in kidney transplant patients that have no episodes of rejection were associated with decreased plasma levels of mmp-9 . we also determined that the increased levels of shla - g dimers linked to the lower levels of proinflammatory cytokines , suggesting the potential role of shla - g dimers in controlling the accompanying inflammatory state . from these findings , shla - g dimers might be useful as a potential marker to control rejection and the inflammatory status of human kidney allotransplants . we enrolled kidney transplant recipients in the study , of which 50 had no evidence of rejection ( nr ) and 17 had chronic rejection ( cr ) . kidney recipients in both categories had similar distribution with respect to gender , age , and race . the distribution of donor source ( living or deceased ) , cold ischemia time , primary cause of renal failure , and immunosuppressive treatment between each group of recipients was not statistically different . average creatinine levels of cr patients were significantly higher than nr patients ( p < 0.05 ) . the protocol was approved by the human assurance committee of georgia regents university , and written informed consent was obtained from all subjects in the study . pbmcs and red blood cells were isolated from buffy coats using histopaque 1077 ( sigma - aldrich , st . total protein of plasma samples was measured using the bradford method ( bio - rad , richmond , ca , usa ) . diluted ( 1 : 50 ) plasma samples were loaded onto 10% gelatin gels , and electrophoresis was performed at 100 constant voltages . gels were washed twice with 2.5% triton - x for 20 min and then incubated at 37c overnight in zymography development buffer ( bio - rad ) . the following day , to visualize the bands , gels were stained with coomassie brilliant blue dye ( bio - rad ) for 3 hrs and destained with destaining solution for 45 min . the gels were rehydrated in water overnight , then scanned and analyzed using imagej program developed at the national institutes of health ( usa ) . depletion of unwanted proteins that could interfere with the immunoprecipitation of hla - g from plasma was achieved using proteoprep immunoaffinity albumin and igg depletion kit ( sigma - aldrich ) following the manufacturer 's protocol . 100 l of depleted plasma were mixed with 100 l of cold ripa buffer and incubated on ice for 15 min . 20 l of protein g bead slurry was added to the plasma lysate , then incubated at 4c for 60 min and centrifuged at 10,000 g for 10 min . 2 l of mem - g/9 mab ( santa cruz biotechnology , dallas , tx , usa ) was added to the supernatant and the mixture was incubated at 4c overnight . after incubation , 50 l of protein g bead slurry was added to the plasma lysate , incubated at 4c for 1 hr , and centrifuged at 10,000 g for 30 sec . the mixture was denatured at 95c for 5 min and centrifuged at 10,000 g for 5 min . 30 l of immunoprecipitated plasma was separated on 10% running gel and 5% stacking gel and transferred to pvdf membrane . the membrane was blocked with 5% bsa and incubated with mem - g/9 primary mab , followed by goat anti - mouse igg - hrp secondary ab ( santa cruz biotechnology ) . quantification of blotted proteins was determined by densitometry analysis of scanned films using imagej software . cytokine and chemokine plasma levels were measured using the multi - analyte elisarray kits ( qiagen , valencia , ca , usa ) according to the manufacturer 's recommendations . the array kits are designed for the simultaneous detection of up to 12 pro- and anti - inflammatory cytokines and chemokines ( il1 , il1 , il2 , il4 , il6 , il8 , il10 , il12 , il17a , ifn , tnf , and gm - csf ) . pbmcs from both groups of patients ( nr and cr ) were treated with human trustain fcx ( fc receptor blocking solution ; biolegend , san diego , ca , usa ) and stained using fluorochrome - conjugated human - specific mabs against cd3 , cd4 , cd8 , cd14 , cd19 , and hla - g . all mabs were purchased from bd biosciences ( san jose , ca , usa ) or from biolegend . cytometry was performed on a cytometer facscanto ( bd , franklin lakes , nj , usa ) and data were analyzed using flowjo software ( tree star inc , ashland , or , usa ) or cell quest software ( bd biosciences ) . some results are expressed as percentage of positive cells obtained with specific ab compared to irrelevant isotype - matched ab . statistical analysis was performed using ncss ( ncss llc , kaysville , utah , usa ) and graphpad ( graphpad inc . , normality and continuous numeric data was checked using the kolmogorov - smirnoff one - sample test , and comparisons were performed by student 's t test or by mann - whitney u test when appropriate . in this study we evaluated the levels of monomer and dimer forms of shla - g1 and hla - g5 isoforms in patients with nonrejected ( nr ) and chronic rejected ( cr ) kidney allografts . immunoprecipitation and western blot analysis of plasma patients resulted in the discovery of two bands ; one corresponding to the expected molecular mass of 39 kda , which represents the shla - g monomer , and one approximately twice that ( shla - g dimer ) ( figure 1(a ) ) . the supernatant from hla - g5-transfected 721.221 human lymphoblastoid cells was used as a positive control . both forms of shla - g had been determined in the plasma of nr and cr patients , and there was considerable variation in shla - g levels within each group . however , the level of total shla - g was significantly higher ( p = 0.03 ) in nr compared with cr kidney transplant patients ( figure 1(b ) ) . in addition , the level of the monomer form of shla - g was slightly higher in the nr group compared with the cr group ( figure 1(c ) ) . we determined that the dimer form of shla - g was dominant in the plasma of both groups of patients . moreover , the level of the dimer form of shla - g was significantly elevated ( p = 0.03 ) in the nr group of patients ( figure 1(d ) ) . these data indicate that the dimer form of shla - g is present and dominates in the plasma of kidney transplant patients . it is known that shla - g proteins can be generated by two mechanisms : alternative splicing and proteolytic release , which is mediated by metalloproteases . to determine the potential contribution of the membrane - bound form of hla - g1 shedding into the pool of shla - g molecules in plasma patients , the expression of hla - g1 on the cell surface of peripheral monocytes and t and b cells has been analyzed in both groups of patients . there was no significant difference in the number of hla - g1-positive t cells and b cells between nr and cr patients ( figures 2(a ) and 2(d ) and data not shown ) . overall , in both groups of patients , hla - g1-positive cells represent a small fraction ( 26% of the total ) of t and b cells . as expected , the majority of hla - g1-positive cells in the peripheral blood of both nr and cr patients were determined in the population of monocytes ( figures 2(a ) , 2(b ) , and 2(c ) ) . however , the number of hla - g1-positive monocytes was significantly elevated ( p = 0.002 ) in the nr patients , but not in the cr patients ( figure 2(e ) ) . these data revealed that the increased expression of hla - g1 on monocytes from nr patients might have a substantial contribution to the elevated plasma levels of shla - g monomer and dimer forms in those patients . since one of the mechanisms of the production of shla - g involves shedding of the membrane - bound form of hla - g1 by metalloproteases and since mmps play a crucial role this class of enzymes , we investigated the levels of mmp-2 and mmp-9 in the plasma of kidney transplant patients . zymography analysis of transplant patients showed the presence of two bands at 68 kda and 90 kda , which correspond to mmp-2 and mmp-9 , respectively ( figure 3(a ) ) . as shown in figure 3(a ) , plasma from both groups of patients contains substantial amounts of mmp-2 and mmp-9 , with no significant difference in the plasma levels of mmp-2 and mmp-9 between nr and cr patients ( figures 3(c ) and 3(d ) ) . however , a tendency toward elevation of mmp-9 levels was observed in the cr kidney transplant patients ( figure 3(d ) ) . since plasma from both the nr and cr groups of patients contains shla - g , this data additionally support the possibility that mmps might play a role in contributing to the pool of total shla - g by shedding the membrane - bound hla - g1 molecules . since hla - g , mmp-2 , and mmp-9 are all involved in regulation of the inflammatory response by modulation of cytokines and chemokines and the inflammatory response represents a critical stage in rejection or survival of allogeneic transplants , we next determined the levels of proinflammatory cytokines in kidney transplant patients . we thus investigated whether the plasma level of proinflammatory cytokines differs between nr and cr kidney transplant patients . for this purpose , we have used a multi - analyte elisarray kits designed to simultaneously assess the levels of 12 pro- and anti - inflammatory cytokines and chemokines ( il1 , il1 , il2 , il4 , il6 , il8 , il10 , il12 , il17a , ifn , tnf , and gm - csf ) . there was considerable variation in cytokines levels within both the nr and cr patients , especially for il-1 , il-4 , il-12 , and ifn- ( figure 4 ) . however , the cr kidney transplant patients had significantly elevated levels of proinflammatory cytokines il-2 ( p = 0.005 ) , il-1 ( p = 0.05 ) , and il-6 ( p = 0.05 ) ( figure 4 ) . these data support our observation that the dimer form of shla - g associates with control of inflammatory responses in kidney transplants patients . hla - g is natural molecule involved in the establishment and maintenance of maternal tolerance to fetal semiallogeneic tissues . hla - g binds to several immune cell inhibitory receptors , for example , ilt2 , ilt3 , and ilt4 , to downmodulate immune responses of myelomonocytic cells , t cells , b cells , and nk cells . limited polymorphisms , restricted tissue expression , and a relatively restricted peptide presentation make hla - g a unique molecule , unlike the classical hla class i molecules . recently , another unusual characteristic of hla - g has been discovered : its ability to form a disulfide - linked dimer form both in solution and at the cell surface . hla - g , unlike most other mhc class i molecules , has two free cysteine residues located in positions 42 and 147 in extracellular domains 1 and 2 , respectively . hla - g molecules refolded in vitro form a disulfide - linked dimer with an intermolecular cys42-cys42 disulfide bond . soluble hla - g5 molecules expressed by human 293 t cells also form disulfide - linked dimeric and additional oligomeric forms , which can reduce the level of cd8 expression on cytotoxic t lymphocytes ( ctls ) . the efficiency of inhibitory signaling is dependent upon several factors , including the stability and avidity of the ligand and its proper structural orientation , which significantly affects the affinity and signaling to targeted inhibitory receptors . mutagenesis studies of the free cysteines suggested that the hla - g dimer more efficiently inhibits nk killing than the monomer and increases the efficiency of ilt2 signaling [ 32 , 42 , 43 , 48 ] . experimental data from several groups , including our laboratory , suggest that hla - g dimer has increased avidity and proper structural orientation to induce efficient inhibitory signaling during ligation with human ilt2 and ilt4 , and murine pir - b - inhibitory receptors [ 32 , 44 , 45 ] . this makes hla - g dimer as the most powerful ligand form for modulation of inflammatory and alloimmune responses in several pathological conditions , including the prolongation of kidney allograft survival or graft acceptance . many studies have been designed to determine shla - g in the plasma or serum of patients suffering from various diseases . shla - g levels were determined in spontaneous miscarriages , in autoimmune diseases , in solid organ transplantation , and in various malignancies . in almost all the studies , unfortunately , the available shla - g elisa determines the total amount of shla - g protein only , which includes both monomer and dimer forms . since the dimer represents the most powerful form of shla - g , it is very critical to analyze the levels of shla - g dimer in healthy and disease conditions . to date , no study has investigated whether hla - g disulfide - linked homodimers are present in plasma from kidney transplant patients . here we show that shla - g dimers are present in plasma from kidney transplant patients . the levels of shla - g dimer were significantly elevated in patients with no rejection episodes compared with patients with chronic rejection , indicating the association of shla - g dimers with the prolongation of kidney allograft survival . in support of that , similar levels of expression and percent of immune inhibitory receptor ilt2- and ilt4-positive cells has been determined on monocytes and t and b cells in both groups of patients ( data not shown ) . this clinical finding is in agreement with our previous study using animal models demonstrating that hla - g dimers prolong the survival of allogeneic skin transplants in ilt transgenic mice ( [ 32 , 49 , 50 ] and unpublished data ) . in the future , it will be important to determine the percentages of shla - g1 and shla - g5 dimers in total shla - g . however , to date , there is no data available demonstrating that shla - g1 and shla - g5 dimers have different binding and/or different efficiency to induce inhibitory receptor signaling . our results show that the number of hla - g1-positive monocytes is significantly increased in nr patients , indicating that the percent of shla - g1 dimer might have been elevated within the total level of shla - g dimers in plasma of the patients with no episodes of rejection . recently , rizzo et al . demonstrated an effective link between mmp-2 and hla - g1 shedding in 721.221-g transfected cell line , jeg3 cell line , and il-10-treated pbmcs from five healthy donors using an in vitro experiments . however , the process of shedding and especially dimerization of shla - g1 in vivo and in pathological conditions , including kidney transplant patients , could be affected by several factors and requires additional investigation . the anti - inflammatory effects of shla - g dimers represent a new finding for this form of hla - g . recently published data by kuroki et al . demonstrating that in an animal model of collagen - induced arthritis , hla - g dimer interacting through a murine ilt homologue , the pir - b receptor exhibited significantly more anti - inflammatory effects compared to monomer . to date , no data is available on studies of the anti - inflammatory effect of shla - g dimers in clinical applications . we demonstrate here that an increased level of shla - g dimers in kidney transplant patients with no rejection episodes is linked to significantly lower levels of proinflammatory cytokines il-2 , il-1 , and il-6 . it will be important to dissect the mechanisms of shla - g dimers controlling inflammatory responses . the anti - inflammatory effect of shla - g dimers opens a new strategy to generate useful agents to control inflammatory responses with minimal side effects . in conclusion , our study shows that shla - g dimers are associated with better survival of kidney allografts and control of the accompanying inflammatory response in kidney transplant patients . thus shla - g dimers can be a potential biomarker to control human alloimmune and inflammatory responses .

human leukocyte antigen - g ( hla - g ) contributes to acceptance of allografts in solid organ / tissue transplantation . most studies have determined that soluble hla - g isoforms are systematically detected in serum / plasma of transplanted patients with significantly fewer episodes of acute and/or chronic rejection of allogeneic tissue / organ . current models of the interactions of hla - g and its specific receptors explain it as functioning in a monomeric form . however , in recent years , new data has revealed the ability of hla - g to form disulfide - linked dimeric complexes with high preferential binding and functional activities . limited data are available on the role of soluble hla - g dimers in clinical pathological conditions . we describe here the presence of soluble hla - g dimers in kidney transplant patients . our study showed that a high level of hla - g dimers in plasma and increased expression of the membrane - bound form of hla - g on monocytes are associated with prolongation of kidney allograft survival . we also determined that the presence of soluble hla - g dimers links to the lower levels of proinflammatory cytokines , suggesting a potential role of hla - g dimers in controlling the accompanying inflammatory state .

the combination of light weight , strong covalent bonds , and low dimensionality gives carbon nanostructures , such as graphene and nanotubes , superior mechanical and thermal properties @xcite , making them interesting candidate materials for thermal management @xcite and phononics applications @xcite . extremely high , possibly divergent , thermal conductivity ( @xmath0 ) of a two - dimensional ( 2d ) phonon gas was predicted by klemens and pedraza ten years before single layer graphene was isolated for the first time @xcite . the first measurements in suspended graphene at about room temperature confirmed klemens and pedraza s predictions , reporting values of @xmath0 in the range @xmath1 wm@xmath2k@xmath2 @xcite . later experiments found @xmath3 wm@xmath2k@xmath2at @xmath4 k , and @xmath5 wm@xmath2k@xmath2at @xmath6 k @xcite . recent measurements on suspended graphene in vacuum yield @xmath0 in the range @xmath7 wm@xmath2k@xmath2at @xmath4 k @xcite . in spite of the efforts to refine these measurements , an accurate determination of @xmath0 remains a tough experimental challenge @xcite . a fundamental reason for such difficulty is that heat transport in graphene is very sensitive to defects and experimental conditions . for example , when graphene is supported on a substrate @xmath0 is reduced to @xmath8 wm@xmath2k@xmath2at room temperature due to phonon scattering from the substrate @xcite . @xmath0 can vary by as much as 50@xmath9 at room temperature as a function of the isotopic composition of graphene @xcite , and was found to be sensitive also to the lateral dimension of measured patches @xcite and to the presence of wrinkles , which may lower @xmath0 by @xmath10 @xcite . this high sensitivity can be advantageous because it offers the possibility to manipulate @xmath0 in graphene - based devices either by tuning the concentration of defects and mass disorder during growth or by imposing controlled external conditions . high and tunable thermal conductivity for a single sheet of atoms opens up the possibility of application in a range of thermal management devices , from high - power electronics @xcite all the way to thermoelectric applications @xcite . in pristine graphene at room temperature , heat is conducted almost exclusively by phonons @xcite , so we can focus on lattice thermal conductivity . both lattice dynamics ( ld ) calculations @xcite and molecular dynamics ( md ) studies @xcite indicate that @xmath0 of suspended graphene converges with system size , in contrast with ideal 2d models , for which @xmath0 diverges logarithmically @xcite . flexural phonons ( out - of - plane vibrational modes ) play a decisive role both as heat carriers and as scatterers . nevertheless , some of these works report very diverse numerical results , stemming from the use of different methods relying on different approximations , and from the choice of various interatomic potentials . theoretical studies suggest that it is possible to control @xmath0 in graphene by applying mechanical ( tensile ) strain , however simulations have given contradictory results . recent _ ab initio _ ld calculations showed that , while @xmath0 is finite for unstrained suspended graphene , it diverges when tensile strain is applied @xcite . in contrast , md results point in the opposite direction , indicating a reduction of @xmath0 upon strain @xcite . even though discrepancies between ld and md results are expected , as the two methods rely upon different approximations @xcite , it is unusual to get such differences in trends . in fact , in ld calculations anharmonic interactions are usually truncated at the first order , while in md simulations quantum effects can not be taken into account , so phonon populations obey to classical statistics . both approximations conspire to make @xmath11 larger than @xmath12 . in this work we report the results of equilibrium molecular dynamics ( emd ) simulations of heat transport in suspended graphene as a function of strain and isotopic mass disorder . we begin by investigating size convergence of @xmath0 in isotopically pure unstrained graphene , and then we study the effects of mechanical strain and isotopic disorder . our goal is to verify whether the divergence , predicted by ld calculations on isotropically strained graphene , also occurs upon uniaxial strain at finite temperature . we also probe how the combination of strain and mass disorder affects @xmath0 . a microscopic interpretation of the results is provided in terms of phonon populations and lifetimes computed at finite temperature . we compute the thermal conductivity of graphene by emd simulations in models with periodic boundary conditions . we use the tersoff empirical potential @xcite recently re - parametrized to accurately reproduce the vibrational properties of carbon nanostructures @xcite . anharmonic ld calculations employing this set of parameters result in a thermal conductivity @xmath13 wm@xmath2k@xmath2for a @xmath14 @xmath15 m graphene flake at @xmath16 k , well within the range of experimental measurements . md production runs are performed in the microcanonical ensemble , starting from initial configurations equilibrated at the target temperature @xcite . temperatures between 300 and 1000 k are considered . the equations of motion are integrated with a 1 fs time step . the cell parameters are optimized at the simulation temperature to achieve zero stress in the ( zig - zag ) direction , perpendicular to the strained one . following linear response theory , @xmath0 is computed from the integral of the autocorrelation function of the heat flux @xmath17 in a microcanonical simulation , according to the green - kubo formula @xcite @xmath18 where @xmath19 is boltzmann s constant , @xmath20 is the temperature and @xmath21 the volume , which is here defined as the surface area of the graphene foil times a nominal thickness of @xmath22 . in practice , @xmath0 is taken as the stationary value of eq . ( [ eq : greenkubo ] ) before it drifts due to accumulated statistical noise . although @xmath0 is in general a tensor , the hexagonal symmetry of graphene yields @xmath23 and @xmath24 . the limits to infinite time and infinite volume in eq . ( [ eq : greenkubo ] ) indicate that size convergence and phase space sampling have to be carefully considered . this aspect is particularly important for low - dimensional systems , for which transport coefficients usually diverge @xcite . therefore , investigating size and time convergence is not merely a technical aspect , but it brings important physical insight . in order to effectively sample the phase space and achieve statistical accuracy in evaluating eq . ( [ eq : greenkubo ] ) , each reported value of @xmath0 is obtained by averaging over at least @xmath25 independent simulations of at least @xmath26 ns . to check size convergence we perform simulations with approximately square supercells of increasing size . we consider systems made of from @xmath27 to @xmath28 atoms . the smallest supercell is @xmath29 @xmath30 and the largest one @xmath31 @xmath30 . fig . [ fig : gk1 ] shows the calculated thermal conductivity as a function of the number of atoms in the simulation cell . the anisotropy between the in - plane thermal conductivities seen for the smallest cell ( @xmath27 atoms ) is due to an uneven and insufficient sampling of the vibrational modes in the two directions . as the cell size is increased a better sampling is achieved , and the anisotropy vanishes . we find that a @xmath32 @xmath30 simulation cell , containing @xmath33 atoms , is required to obtain a converged value @xmath34 wm@xmath2k@xmath2 . our estimate of @xmath0 is lower than the values reported in recent works , in which smaller systems were simulated @xcite . the inset in fig . [ fig : gk1 ] displays the normalized heat flux autocorrelation functions ( hfacf ) for several simulations with different cell sizes , showing that in all cases the time decay is faster than @xmath35 , which guarantees convergence of eq . ( [ eq : greenkubo ] ) . we can conclude that @xmath0 of unstrained graphene at finite temperature is finite and converges with size , confirming the prediction of former _ ab initio _ ld calculations @xcite . classical calculations of @xmath0 far below the debye temperature ( @xmath36 for graphene ) may yield large differences with respect to calculations taking into account the proper quantum statistics for phonons . two effects contribute to such differences , yet in opposite directions : classical calculations give shorter phonon lifetimes than quantum calculations , but classical phonon heat capacities are always larger than quantum ones . ld calculations showed that in graphene at room temperature these two effects compensate to the point that classical @xmath0 underestimates quantum @xmath0 only by about 10@xmath9 @xcite . wm@xmath2k@xmath2is achieved for a cell with @xmath33 atoms . inset : time decay of the normalized heat flux autocorrelation functions ( hfacf ) for @xmath37 , @xmath33 , and @xmath38 atom cells . all hfacf decay faster than @xmath35 . ] in the zig - zag direction ( red ) . dispersion curves are computed in the strained armchair direction ( @xmath39-m ) and in the stress - free zigzag direction ( @xmath39-k ) . wavevectors are in units of the inverse lattice constant @xmath40 , rescaled according to applied strain . ] the observed size convergence of @xmath0 from above , provides an insight into the contribution of flexural phonons to thermal transport in graphene . convergence trends can be interpreted by referring to the dispersion relations of phonons in graphene , computed in the harmonic approximation by diagonalizing the dynamical matrix @xcite ( fig . [ fig : dispersions ] ) . accurate md calculations of the thermal conductivity of graphene or carbon nanotubes require a converged sampling of the low - frequency acoustic flexural ( za ) modes @xcite . whereas the contribution to @xmath0 of in - plane acoustic modes converges relatively fast , good sampling of the za modes is achieved only for large simulation cells because of their quadratic dispersion relation near the @xmath39 point . za modes are expected to provide a significant contribution to heat transport , and have been identified as the majority heat carriers @xcite . however , close to the @xmath39 point their group velocity vanishes and their main role in thermal transport is to scatter other heat carriers . our convergence trends indeed show that the overall effect of low - frequency za modes is to lower the in - plane thermal conductivity of graphene . in fact , performing simulations on ` 2d graphene ' , i.e. , a graphene sheet in which atoms move only in plane , we observe logarithmic divergence of @xmath41 , as shown in fig . [ fig : k.vs.time.2d3d ] , in accordance with theoretical and numerical studies on 2d model systems @xcite . our results demonstrate the dual role of za modes , which is to provide an important reservoir of heat carriers , as well as the main scattering channel that prevents the divergence of @xmath0 @xcite . for the 2d case , yielding @xmath42 divergence of @xmath0 . ] strain affects the vibrational properties of materials , as it modifies phonon dispersion relations . speed of sound , frequency range , scattering rates , and therefore thermal conductivity , are all altered . we apply uniaxial tensile strain along the armchair direction and relax the simulation cell to achieve zero stress in the perpendicular ( zigzag ) direction . the dispersion relations of strained graphene ( strain @xmath43 ) are compared to the unstrained ones in fig . [ fig : dispersions ] . in the low - frequency range the most significant changes is the linearization of the dispersion relation of the za mode along the strain axis . in the direction perpendicular to the strain axis the za branch remains unchanged . this implies non - vanishing group velocity for the za modes propagating along the strain axis . in addition , in - plane acoustic modes are slightly softened in both directions . in the high - frequency range the degeneracy of the zone center optical phonon is broken , in accordance with raman measurements.@xcite fig . [ fig : kappa.strain ] shows the thermal conductivity of graphene as a function of time , calculated as the argument of the time limit in eq . ( [ eq : greenkubo ] ) , along the strained direction for strain up to @xmath44 . for small strain ( @xmath45 ) , the thermal conductivity in the strained direction still converges , yet to a larger value than in the unstrained case . as strain is increased ( @xmath46 in the figure ) , the thermal conductivity along the strained direction tends to diverge . the same behavior is observed for a larger simulation cell containing more than @xmath47 atoms . the inset in fig . [ fig : kappa.strain ] displays the time decay of the respective hfacf . for @xmath48 , the hfacf decays faster than @xmath35 . however , at larger strain the hfacf decays as @xmath35 , such that @xmath0 diverges as @xmath42 , following the standard behavior of transport coefficients in 2d systems @xcite . meanwhile , the thermal conductivity in the stress - free direction does not diverge for thermal conductivity parallel and perpendicular to strain direction , thermal conductivity of isotropically strained graphene at @xmath49 k , vdos of strained and unstrained graphene , and a comparison of phonon populations in the presence of strain and isotopic mass disorder . ] . in fact , the thermal conductivity perpendicular to the strain direction is slightly reduced , due to a mild softening of the in - plane acoustic modes as shown in fig . [ fig : dispersions ] . it is important to point out that a logarithmic divergence of @xmath0 with size in finite 2d model systems under stationary non - equilibrium conditions implies a logarithmic divergence of @xmath0 as a function of time in periodic systems at equilibrium and _ vice versa _ @xcite . in other words , a @xmath35 decay of the heat flux autocorrelation function in a periodic system at equilibrium ( in the absence of a temperature gradient ) , implies a logarithmic divergence of @xmath0 with system size under non - equilibrium conditions ( in the presence of a finite temperature gradient ) . therefore , our predictions can ( in principle ) be probed experimentally by measuring the size dependence of the thermal conductivity in strained graphene samples . _ ab initio _ ld calculations predict divergence of @xmath0 in isotropically strained graphene for any amount of applied strain @xcite . md simulations of isotropically strained graphene at @xmath49 k suggest that @xmath0 diverges already for @xmath50 , confirming the predictions from ld @xcite . in contrast , uniaxial strain and finite temperature limit divergence to relatively large strain @xmath46 , whereas at lower strain @xmath0 remains finite . simulations at @xmath51 k confirm the divergence of @xmath0 along the direction of strain persists for @xmath46 , evidencing no significant difference with respect to the trends observed at room temperature . in this higher temperature regime , even though far below the debye temperature of graphene , classical phonon populations approach quantum populations , and quantum effects are mitigated . since phonon lifetimes computed with classical statistics are usually underestimated with respect to those obtained with the correct quantum statistics @xcite , we can safely argue that the divergent nature of @xmath0 in strained graphene is not an artifact of classical md . \(a ) + k and ( b ) @xmath52 k , calculated from eq . ( [ eq : greenkubo ] ) . the dashed horizontal lines indicate the average @xmath0 for unstrained graphene . the inset shows the time decay of the normalized hfacf . for high strain , the hfacf decays as @xmath35 such that @xmath0 diverges as @xmath42 as observed in the main panel.,title="fig : " ] + ( b ) + k and ( b ) @xmath52 k , calculated from eq . ( [ eq : greenkubo ] ) . the dashed horizontal lines indicate the average @xmath0 for unstrained graphene . the inset shows the time decay of the normalized hfacf . for high strain , the hfacf decays as @xmath35 such that @xmath0 diverges as @xmath42 as observed in the main panel.,title="fig : " ] from both analytical models and ld calculations , it appears that the cause for the divergence of @xmath0 lies in the linearization of long - wavelength za modes ( fig . [ fig : dispersions ] ) . such alteration of the dispersion relations affects phonon populations , which are probed by computing the vibrational density of states ( vdos ) of strained and unstrained samples . our calculations indeed show a depletion of the vdos for the za modes in the frequency range from @xmath53 thz up to @xmath54 thz @xcite . -m ) are shown . lifetimes at small wavevectors @xmath55 diverge for the 4% strained model . the 1/q decay is shown ( dashed line ) for reference . ] these changes have dramatic effects on phonon lifetimes ( fig . [ fig : lifetimes ] ) , which diverge for large strain and lead to divergence of the thermal conductivity . using the solution of the linearized boltzmann transport equation in the relaxation time approximation , one can express @xmath0 for a periodic system of finite size as the sum of the contributions of each phonon mode , as @xmath56 . here @xmath57 is the specific heat of mode @xmath58 , @xmath59 its group velocity , and @xmath60 its lifetime . since @xmath61 and @xmath57 are always finite , divergence of @xmath0 implies divergence of @xmath60 for some of the modes . phonon lifetimes are computed here as the decay time of the autocorrelation function of the energy of the normal modes in microcanonical md simulations @xcite . we indeed observe the presence of za modes with slowly decaying correlation functions when @xmath62 is larger than 2@xmath9 , which imply diverging @xmath63 . the trends of @xmath64 ( fig . [ fig : lifetimes ] ) permit the extrapolation of our results to extended systems , for which @xmath0 is expressed in integral form : @xmath65 where the integral is taken over the two - dimensional brillouin zone ( bz ) . the limit for @xmath66 determines whether @xmath0 diverges . in the classical case @xmath67 is a constant , and in general @xmath68 . the group velocity of the za modes along @xmath69 is @xmath70 . for unstrained graphene @xmath71 , whereas when strain is applied along @xmath69 , @xmath72 tends to a constant value . in unstrained graphene @xmath0 would diverge for @xmath73 , while when strain is applied @xmath0 diverges for @xmath74 . our calculations show that @xmath75 increases with strain , reaching @xmath76 for @xmath77 , which is consistent with the observed threshold for @xmath0 divergence . so far we have presented results for isotopically pure graphene ( @xmath78% @xmath79c ) . given the demonstration of graphene growth with customized isotopic composition @xcite , it is also worth investigating the combined effect of strain and controlled isotopic composition on the thermal conductivity of graphene , checking whether its divergence can be suppressed by mass disorder . we consider pure @xmath79c , natural composition ( @xmath80 @xmath81c ) , and @xmath81c enriched graphene models ( 10@xmath9 , 50@xmath9 and 99.2@xmath9 ) . in absence of defects the lattice thermal conductivity is limited by phonon - phonon scattering @xcite , therefore @xmath82 . meanwhile , the scattering of phonons by defects is temperature independent @xcite , so that @xmath83 trends are modified . in fig . [ fig : kappa.vs.t ] we indeed observe @xmath84 for isotopically pure graphene , natural graphene and @xmath85% @xmath81c isotopically enriched graphene , indicating that for the natural isotopic composition the effect of mass disorder is almost negligible . however , as the amount of @xmath81c increases to 10@xmath9 and 50@xmath9 , @xmath0 decreases more slowly with @xmath20 indicating that mass disorder becomes the primary source of phonon scattering . this aspect could be exploited in thermal management devices that operate over wide temperature ranges , where it would be undesirable to have large variations in @xmath0 with @xmath20 . the ratio between @xmath0 for isotopically pure and 50@xmath9 @xmath81c - enriched graphene is about 2 , and agrees well with recent experimental measurements @xcite . c. solid lines are fitted to the data in order to extract the temperature dependence , as reported in the plot . ] even though large variations of @xmath0 as a function of isotopic composition are found , when uniaxial tensile strain is applied the general behavior of @xmath0 for isotopically modified graphene is not qualitatively different from the isotopically pure case . @xmath0 along the strained direction increases for low strain and diverges for @xmath46 even in samples with the highest isotopic disorder ( 50@xmath9 @xmath81c ) , as shown in fig . [ fig : kappa.vs.timec13 ] . the inset shows that above the strain threshold the hfacf decay as @xmath35 and thus @xmath86 . the ratio between phonon populations shows that in isotopically enriched graphene , as in the isotopically pure case , tensile strain induces similar reductions to the population of za modes @xcite . therefore , mass disorder is not sufficient to suppress the divergence of the lifetimes of low - frequency za modes . in fact , these modes have a wavelength of several tens of nm , thus even in the presence of isotopic mass disorder they propagate as in a continuous medium , and are not significantly affected by scattering centers at the atomic scale . it is worth noting that mass disorder can not suppress divergence in non - linear models as well @xcite . k , calculated from eq . ( [ eq : greenkubo ] ) , with a 50@xmath9 concentration of @xmath81c . the dashed horizontal lines indicate the average @xmath0 for the unstrained case . the inset shows the normalized heat flux autocorrelation functions , which decay like @xmath35 for @xmath87% , yielding @xmath42 divergence of @xmath0 . ] in conclusion , we have shown that heat transport in suspended graphene is controlled by za modes , which contribute the essential scattering channels to limit the thermal conductivity in unstrained samples . in fact , in absence of za modes @xmath0 would diverge with size , as in ideal 2d models . uniaxial tensile strain reduces the population of za phonon modes at low frequency , makes their zone center group velocity finite and increases their lifetime , thus causing divergence of the thermal conductivity in the strained direction . we then predict that @xmath0 of strained samples would diverge logarithmically with the size of the samples . it is important to point out that our predictions based on computer simulations are accessible to experiments . in an experimental setup , @xmath0 will always be finite and limited by boundary and defect scattering . nonetheless , by performing measurements in strained samples of increasing size it should be possible to see a logarithmic dependence of @xmath0 as a function of size . the amount of strain required to observe divergence , @xmath88 , might also be within reach of current experimental techniques . we also predict that the presence of isotopic mass disorder does not suppress the divergence of @xmath0 that should be then expected to occur also in samples with natural composition , which are easier to grow than isotopically pure ones . 42ifxundefined [ 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 link:\doibase 10.1038/nmat3064 [ * * , ( ) ] link:\doibase 10.1063/1.2907977 [ * * , ( ) ] link:\doibase 10.1063/1.3183587 [ * * , ( ) ] link:\doibase 10.1021/nl901231s [ * * , ( ) ] link:\doibase 10.1103/revmodphys.84.1045 [ * * , ( ) ] link:\doibase 10.1016/0008 - 6223(94)90096 - 5 [ * * , ( ) ] link:\doibase 10.1021/nl0731872 [ * * , ( ) ] link:\doibase 10.1021/nl9041966 [ * * , ( ) ] link:\doibase 10.1021/nn102915x [ * * , ( ) ] link:\doibase 10.1126/science.1184014 [ * * , ( ) ] link:\doibase 10.1038/nmat3207 [ * * , ( ) ] link:\doibase 10.1021/nl301230 g [ * * , ( ) ] link:\doibase 10.1088/0957 - 4484/23/36/365701 [ * * , ( ) ] link:\doibase 10.1038/ncomms1828 [ * * , ( ) ] link:\doibase 10.1021/nn3031595 [ * * , ( ) ] link:\doibase 10.1103/physrevb.81.205441 [ * * , ( ) ] link:\doibase 10.1103/physrevb.82.115427 [ * * , ( ) ] link:\doibase 10.1063/1.3665226 [ * * , ( ) ] link:\doibase 10.1021/nl202694 m [ * * , ( ) ] link:\doibase 10.1063/1.3246155 [ * * , ( ) ] link:\doibase 10.1063/1.3435465 [ * * , ( ) ] link:\doibase 10.1103/physrevb.81.045413 [ * * , ( ) ] http://www.springerlink.com/index/mh60x378752gv73m.pdf [ * * , ( ) ] link:\doibase 10.1016/s0370 - 1573(02)00558 - 6 [ * * , ( ) ] link:\doibase 10.1103/physreve.86.040101 [ * * , ( ) ] link:\doibase 10.1103/physrevb.81.245318 [ * * , ( ) ] link:\doibase 10.1103/physrevb.79.064301 [ * * , ( ) ] link:\doibase 10.1039/c2cp42394d [ * * , ( ) ] http://link.aps.org/doi/10.1103/physrevlett.61.2879 [ * * , ( ) ] link:\doibase 10.1103/physrevb.69.134103 [ * * , ( ) ] link:\doibase 10.1063/1.1740082 [ * * , ( ) ] link:\doibase 10.1143/jpsj.12.570 [ * * , ( ) ] link:\doibase 10.1063/1.1854281 [ * * , ( ) ] link:\doibase 10.1021/nl202118d [ * * , ( ) ] link:\doibase 10.1021/nn200114p [ * * , ( ) ] link:\doibase 10.1103/physrevb.84.115460 [ * * , ( ) ] @noop _ _ ( , , ) link:\doibase 10.1103/physrevlett.99.255502 [ * * , ( ) ] link:\doibase 10.1103/physrevb.79.205433 [ * * , ( ) ] link:\doibase 10.1103/physrevb.34.5058 [ * * , ( ) ] @noop _ _ ( , , )

we investigate the effect of strain and isotopic disorder on thermal transport in suspended graphene by equilibrium molecular dynamics simulations . we show that the thermal conductivity of unstrained graphene , calculated from the fluctuations of the heat current at equilibrium is finite and converges with size at finite temperature . in contrast , the thermal conductivity of strained graphene diverges logarithmically with the size of the models , when strain exceeds a relatively large threshold value of 2% . an analysis of phonon populations and lifetimes explains the divergence of the thermal conductivity as a consequence of changes in the occupation of low - frequency out - of - plane phonons and an increase in their lifetimes due to strain .

Edith Windsor, the gay-rights activist whose landmark case led the Supreme Court to grant same-sex married couples federal recognition for the first time and rights to a host of federal benefits that until then only married heterosexuals had enjoyed, died on Tuesday in Manhattan. She was 88. Her wife, Judith Kasen-Windsor, confirmed the death, at a hospital, but did not specify a cause. They were married in 2016. Four decades after the Stonewall Inn uprising fueled the fight for lesbian, gay, bisexual and transgender rights in America, Ms. Windsor, the widow of a woman with whom she had lived much of her life, became the lead plaintiff in what is widely regarded as the second most important Supreme Court ruling in the national battle over same-sex marriage rights. The Windsor decision, handed down in 2013, was limited to 13 states and the District of Columbia. But in a more expansive ruling in 2015, in Obergefell v. Hodges and three related cases, the Supreme Court held that same-sex couples had a constitutional right to marry anywhere in the nation, with all the protections and privileges of heterosexual couples. Its historic significance was likened to that of Lawrence v. Texas in 2003, which decriminalized gay sex in the United States. ||||| Windsor, known for remaining bubbly and upbeat during her legal battle, contested her estate tax liability after the 2009 death of her longtime wife, Thea Spyer, because the U.S. government did not recognize their Canadian marriage.

– Edith Windsor, the woman behind the legal case that struck down the Defense of Marriage Act and paved the way for the legalization of same-sex marriage, died Tuesday at 88, the New York Daily News reports. The longtime New Yorker and gay-rights activist was the plaintiff in United States v. Windsor, which went before the Supreme Court in 2013. According to the New York Times, the ruling in favor of Windsor was the first time married same-sex couples received federal recognition. It allowed couples in states where same-sex marriage was already legal to receive more than 1,000 federal benefits available to heterosexual couples and struck down the legal definition of marriage as between a man and woman, paving the way for the 2015 case that legalized same-sex marriage nationwide. "The wheels of progress turn forward because of people like Edie who are willing to stand up in the face of injustice," ACLU executive director Anthony Romero says.

acute generalized exanthematous pustulosis ( agep ) is a pustular eruption , mainly drug induced , often accompanied by fever and neutrophilic leukocytosis appearing as scarlatiniform erythema over the flexures evolving into numerous tiny non - follicular pustules . we report a case of agep to the epidermal growth factor receptor ( egfr ) inhibitor , lapatinib . a 56-year old woman presented with erythema , scaling and oozing from the flexures , and erythematous scaly papules and plaques over the back , trunk , thighs and forearms of 4-month duration [ figure 1 ] . the skin lesions had started gradually and increased in extent and intensity in the last 1 month . the periphery of the papules and plaques were studded with pustules [ figure 2 ] . painful lesions resembling pyogenic granuloma were present over the pulp of the right toe and over the proximal nail folds of both thumbs [ figures 3 and 4 ] . she complained of breathlessness , weakness and feverishness inspite of the temperature being normal . in march 2008 , she underwent left mastectomy for ductal carcinoma breast ( her-2 receptor 3 + - strongly positive ) with supraclavicular metastasis detected in may 2009 . she developed the lesions described above two months after initiating treatment with the two drugs . upon developing skin lesions , discrete and confluent scaly , erythematous papules over the back scarlatiniform erythema of the flexures , with the periphery of the papules and plaques showing pustules painful pyogenic granuloma - like lesions over the right toe painful pyogenic granuloma - like lesions over the proximal nail folds of the thumbs clinically , pustular psoriasis and agep were considered in the differential diagnoses . lapatinib was withheld for a week and she was treated with topical corticosteroids and antihistamines ( amitryptiline ) for the burning pain over the finger and toe pulps . investigations revealed anemia ( hb-9.6 g % ) and increased polymorphs ( 80% ) , total count- 10.310/l . biopsy of the pustule and plaque revealed subcorneal and intraspinous collection of neutrophils with spongiosis , upper dermal edema , perivascular inflammatory cell infiltrate of neutrophils , lymphocytes and eosinophils , neutrophilic vasculitis and extravasation of rbc confirming agep [ figures 5 and 6 ] . subcorneal and intraspinous collection of neutrophils with spongiosis , upper dermal edema , perivascular inflammatory cell infiltrate of neutrophils , lymphocytes and eosinophils , neutrophilic vasculitis and extravasation of rbc ( h&e , 10 ) dermis with vasculitis and extravasation of rbcs ( h&e , 40 ) after the withdrawal of lapatinib , lesions showed clearing , but she was advised by the oncologist to restart the medication at a lower dose ( from 1250 to 750 mg ) . as lapatinib was reintroduced while lesions were clearing , they recurred on restarting lapatinib but were less severe . systemic prednisolone 30 mg / day , tapered to 10 mg / day over a month , was administered to control the reaction and she was reasonably controlled with this maintenance dose 1 month later , but for erythema and few lesions over the flexures [ figure 7 ] . her breathlessness and feverishness subsided and the pyogenic granuloma - like lesions over the proximal nail folds and over the pulp of the toe showed signs of resolution [ figures 8 and 9 ] . she subsequently stopped the medication on her own and achieved complete clearance of the erythema . the pyogenic - granuloma - like lesions resolved completely . skin lesions resolving after withdrawal of lapatinib and institution of systemic corticosteroids lesion over the pulp of right toe showing resolution resolution of lesions over the proximal nail folds lapatinib is an oral dual kinase inhibitor belonging to the egfr antagonist group of drugs targeting both the erbb1 and erbb2 receptors . epidermal growth factor receptor or erbb1 is a member of the erbb family is a 170-kd transmembrane protein with an extracellular ligand - binding domain and an intracellular protein tyrosine kinase . upon ligand binding , the phosphorylated protein kinase activates a signal transduction pathway regulating proliferation , differentiation , migration and apoptosis of cells . erbb1 ( or her-1 ) is overexpressed in 27 - 30% of breast tumors and erbb2 ( or her-2 ) is overexpressed in 20 - 25% of breast cancers . lapatinib , a dual tyrosine kinase inhibitor has shown efficacy in breast cancer and as a result its use has been approved , in combination with capecitabine , for the treatment of disease positive for the human egfr . the most frequent adverse effects of lapatinib include diarrhea , rash , nausea and fatigue . the skin rash is characterized by papules and pustules over the face , chest and back resembling folliculitis or an acneiform drug eruption . this appears within 1 and 3 weeks of treatment and peaks at about the fifth week , subsiding within 4 weeks of withdrawal of treatment . dermatologic adverse reactions to egfr inhibitors include follicular or pustular lesions , painful periungual granulation - type or friable pyogenic granuloma - like changes , fissures of the lateral nail folds and/or distal finger tufts , hair changes , dry skin , hypersensitivity reactions and mucositis . our patient had non - follicular pustules and scarlatiniform erythema and scaling with marked accentuation over the flexures , with sparing of the face and seborrheic areas clinically suggestive of agep which was confirmed by histopathology . the skin rash associated with the skin toxicity of egfr inhibitors is follicular and involves the face and seborrheic areas . the painful pyogenic granuloma - like lesions of the proximal nail folds and finger pulp are possibly related to the skin toxicity of lapatinib also described with other egfr inhibitors . pustular psoriasis was considered in the differential diagnosis , but the presence of eosinophils in addition to intraspinous collections of neutrophils and the rapid clearance of lesions after withdrawal of lapatinib , and recurrence after reintroduction favored the diagnosis of agep . also after lapatinib was stopped by the patient on her own leucocytoclastic vasculitis is also reported in a few cases of agep and is not seen in pustular psoriasis . serious adverse skin reactions like stevens - johnson syndrome and agep have been reported with imatinib , a multikinase inhibitor which is a first - line therapy for chronic myeloid leukemia . to date , four cases of imatinib - induced agep have been described and in one patient this been referred to as " scarlatiniform erythema with non - follicular pustules confined to flexural areas . " another patient had " fever , exfoliative dermatitis , and non - follicular pustules . " all these patients developed the eruption within 1 - 3 months after the start of imatinib therapy . imatinib induces agep via inhibition of tyrosine kinases by a mechanism similar to that seen in mercury - induced agep . various adverse reactions have been reported with multikinase inhibitors , whereas reported reactions to egfr inhibitors have been comparatively milder . although agep has been reported with imatinib ( a multikinase inhibitor ) , there have been no reports of serious reactions with lapatinib , an egfr inhibitor . this case could represent the first case report of agep to the egfr inhibitor , lapatinib .

acute generalized exanthematous pustulosis ( agep ) is a pustular eruption , mainly drug induced often accompanied by fever and neutrophilic leukocytosis presenting as scarlatiniform erythema over the flexures evolving into numerous tiny non follicular pustules . we present a case report of a 56-year old woman , who had undergone mastectomy , treated with lapatinib for metastatic disease , and who presented with multiple erythematous papules and plaques with peripheral pustules . she also developed painful pyogenic granuloma - like lesions over the pulp of toe and over the proximal nail folds.all the lesions subsided following withdrawal of lapatinib . although agep has been reported with imatinib ( a multikinase inhibitor ) , there have been no reports of serious reactions with lapatinib , an egfr inhibitor . this case could represent the first case report of agep to the egfr inhibitor , lapatinib .

SECTION 1. SHORT TITLE. This Act may be cited as the ``National Transportation Safety Board Reauthorization Act of 2003''. SEC. 2. AUTHORIZATION OF APPROPRIATIONS. (a) Fiscal Years 2003-2006.--Section 1118(a) of title 49, United States Code, is amended-- (1) by striking ``and''; and (2) by striking ``such sums to'' and inserting the following: ``$73,325,000 for fiscal year 2003, $78,757,000 for fiscal year 2004, $83,011,000 for fiscal year 2005, and $87,539,000 for fiscal year 2006. Such sums shall''. (b) Emergency Fund.--Section 1118(b) of such title is amended by striking the second sentence and inserting the following: ``In addition, there are authorized to be appropriated such sums as may be necessary to increase the fund to, and maintain the fund at, a level not to exceed $4,000,000.''. (c) NTSB Academy.--Section 1118 of such title is amended by adding at the end the following: ``(c) Academy.-- ``(1) Authorization.--There are authorized to be appropriated to the Board for necessary expenses of the National Transportation Safety Board Academy, not otherwise provided for, $3,347,000 for fiscal year 2003, $4,896,000 for fiscal year 2004, $4,995,000 for fiscal year 2005, and $5,200,000 for fiscal year 2006. Such sums shall remain available until expended. ``(2) Fees.--The Board may impose and collect such fees as it determines to be appropriate for services provided by or through the Academy. ``(3) Receipts credited as offsetting collections.-- Notwithstanding section 3302 of title 31, any fee collected under this subsection-- ``(A) shall be credited as offsetting collections to the account that finances the activities and services for which the fee is imposed; ``(B) shall be available for expenditure only to pay the costs of activities and services for which the fee is imposed; and ``(C) shall remain available until expended. ``(4) Refunds.--The Board may refund any fee paid by mistake or any amount paid in excess of that required. ``(d) Report on Academy Operations.--The National Transportation Safety Board shall transmit an annual report to the Congress on the activities and operations of the National Transportation Safety Board Academy.''. SEC. 3. ASSISTANCE TO FAMILIES OF PASSENGERS INVOLVED IN AIRCRAFT ACCIDENTS. (a) Relinquishment of Investigative Priority.--Section 1136 of title 49, United States Code, is amended by adding at the end the following: ``(j) Relinquishment of Investigative Priority.-- ``(1) General rule.--This section (other than subsection (g)) shall not apply to an aircraft accident if the Board has relinquished investigative priority under section 1131(a)(2)(B) and the Federal agency to which the Board relinquished investigative priority is willing and able to provide assistance to the victims and families of the passengers involved in the accident. ``(2) Board assistance.--If this section does not apply to an aircraft accident because the Board has relinquished investigative priority with respect to the accident, the Board shall assist, to the maximum extent possible, the agency to which the Board has relinquished investigative priority in assisting families with respect to the accident.''. (b) Revision of MOU.--Not later than 1 year after the date of enactment of this Act, the National Transportation Safety Board and the Federal Bureau of Investigation shall revise their 1977 agreement on the investigation of accidents to take into account the amendments made by this section and shall submit a copy of the revised agreement to the Committee on Transportation and Infrastructure of the House of Representatives and the Committee on Commerce, Science, and Transportation of the Senate. SEC. 4. RELIEF FROM CONTRACTING REQUIREMENTS FOR INVESTIGATIONS SERVICES. (a) In General.--From the date of enactment of this Act through September 30, 2006, the National Transportation Safety Board may enter into agreements or contracts under the authority of section 1113(b)(1)(B) of title 49, United States Code, for investigations conducted under section 1131 of that title without regard to any other provision of law requiring competition if necessary to expedite the investigation. (b) Report on Usage.--On February 1, 2006, the National Transportation Safety Board shall transmit a report to the House of Representatives Committee on Transportation and Infrastructure, the House of Representatives Committee on Government Reform, the Senate Committee on Commerce, Science, and Transportation, and the Senate Committee on Governmental Affairs that-- (1) describes each contract for $25,000 or more executed by the Board to which the authority provided by subsection (a) was applied; and (2) sets forth the rationale for dispensing with competition requirements with respect to such contract. SEC. 5. ACCIDENT AND SAFETY DATA CLASSIFICATION AND PUBLICATION. Section 1119 of title 49, United States Code, is amended by adding at the end the following: ``(c) Appeals.-- ``(1) Notification of rights.--In any case in which an employee of the Board determines that an occurrence associated with the operation of an aircraft constitutes an accident, the employee shall notify the owner or operator of that aircraft of the right to appeal that determination to the Board. ``(2) Procedure.--The Board shall establish and publish the procedures for appeals under this subsection. ``(3) Limitation on applicability.--This subsection shall not apply in the case of an accident that results in a loss of life.''. SEC. 6. SECRETARY OF TRANSPORTATION'S RESPONSES TO SAFETY RECOMMENDATIONS. Section 1135(d) of title 49, United States Code, is amended to read as follows: ``(d) Reporting Requirements.-- ``(1) Annual secretarial regulatory status reports.--On February 1 of each year, the Secretary shall submit a report to Congress and the Board containing the regulatory status of each recommendation made by the Board to the Secretary (or to an Administration within the Department of Transportation) that is on the Board's `most wanted list'. The Secretary shall continue to report on the regulatory status of each such recommendation in the report due on February 1 of subsequent years until final regulatory action is taken on that recommendation or the Secretary (or an Administration within the Department) determines and states in such a report that no action should be taken. ``(2) Failure to report.--If on March 1 of each year the Board has not received the Secretary's report required by this subsection, the Board shall notify the Committee on Transportation and Infrastructure of the House of Representatives and the Committee on Commerce, Science, and Transportation of the Senate of the Secretary's failure to submit the required report. ``(3) Termination.--This subsection shall cease to be in effect after the report required to be filed on February 1, 2008, is filed.''. SEC. 7. TECHNICAL AMENDMENTS. Section 1131(a)(2) of title 49, United States Code, is amended by moving subparagraphs (B) and (C) 4 ems to the left. SEC. 8. DOT INSPECTOR GENERAL INVESTIGATIVE AUTHORITY. (a) In General.--Section 228 of the Motor Carrier Safety Improvement Act of 1999 (113 Stat. 1773) is transferred to, and added at the end of, subchapter III of chapter 3 of title 49, United States Code, as section 354 of that title. (b) Conforming Amendments.--(1) The caption of the section is amended to read as follows: ``Sec. 354. Investigative authority of Inspector General''. (2) The chapter analysis for chapter 3 of title 49, United States Code, is amended by adding at the end the following: ``354. Investigative authority of Inspector General.''. SEC. 9. REPORTS ON CERTAIN OPEN SAFETY RECOMMENDATIONS. (a) Initial Report.--Within 1 year after the date of enactment of this Act, the Secretary of Transportation shall submit a report to Congress and the National Transportation Safety Board containing the regulatory status of each open safety recommendation made by the Board to the Secretary concerning-- (1) 15-passenger van safety; (2) railroad grade crossing safety; and (3) medical certifications for a commercial driver's license. (b) Biennial Updates.--The Secretary shall continue to report on the regulatory status of each such recommendation (and any subsequent recommendation made by the Board to the Secretary concerning a matter described in paragraph (1), (2), or (3) of subsection (a)) at 2-year intervals until-- (1) final regulatory action has been taken on the recommendation; (2) the Secretary determines, and states in the report, that no action should be taken on that recommendation; or (3) the report, if any, required to be submitted in 2008 is submitted. (c) Failure To Report.--If the Board has not received a report required to be submitted under subsection (a) or (b) within 30 days after the date on which that report is required to be submitted, the Board shall notify the Committee on Transportation and Infrastructure of the House of Representatives and the Committee on Commerce, Science, and Transportation of the Senate. Speaker of the House of Representatives. Vice President of the United States and President of the Senate.

National Transportation Safety Board Reauthorization Act of 2003 - (Sec. 2) Amends Federal transportation law to extend the authorization of appropriations for the National Transportation Safety Board (NTSB) for FY 2003 through 2006, including the NTSB Academy and an emergency fund. Authorizes appropriations necessary to increase the emergency fund from $2 million to $3 million. Authorizes the NTSB to impose and collect appropriate fees for services provided by or through the Academy. Credits receipts as offsetting collections to the account that finances Academy activities. Requires an annual report on the activities and operations of the Academy. (Sec. 3) Relieves the NTSB of the duty to render specified assistance to families of passengers involved in an aircraft accident if the NTSB has relinquished its investigative priority to investigate it and the Federal agency to which it has relinquished such priority is willing and able to provide assistance to the victims and families of the passengers. Requires the NTSB, however, even if it has relinquished such priority, to assist, to the maximum extent possible, the agency to which it has relinquished it in assisting families with respect to the accident. Directs the NTSB and the Federal Bureau of Investigation to revise their 1977 agreement on the investigation of accidents to take into account the amendments made by this Act, and to submit such revision to specified congressional committees. (Sec. 4) Allows the NTSB to enter into agreements or contracts necessary to conduct accident investigations without regard to competition requirements if necessary to expedite investigation. Requires that each contract for at least $25,000 be enumerated in the NTSB's annual report to Congress. (Sec. 5) Requires any NTSB employee, whenever heor she determines that an occurrence associated with the operation of an aircraft, but not resulting in a loss of life, constitutes an accident, to notify the aircraft owner or operator of the right to appeal that determination to the NTSB. Requires the NTSB to establish and publish appeal procedures. (Sec. 6) Revises requirements for an annual report to Congress by the Secretary of Transportation on NTSB transportation safety recommendations. Requires the Secretary to report on February 1 of each year to Congress and the NTSB on the regulatory status of each recommendation on the NTSB "most wanted list," until final regulatory action is taken or the Secretary (or an Administration within the Department of Transportation (DOT)) determines and reports that no action should be taken. Requires the NTSB to report to specified congressional committees on March 1 of each year if it has not received the Secretary's report. (Sec. 8) Amends Federal transportation law and the Motor Carrier Safety Improvement Act of 1999 to make certain technical and conforming amendments with respect to the investigative authority of the DOT Inspector General. (Sec. 9) Requires the Secretary to report biennially to Congress and the NTSB on the regulatory status of each NTSB open safety recommendation concerning: (1) 15-passenger van safety; (2) railroad grade crossing safety; and (3) medical certifications for a commercial driver's license. Requires NTSB notification to specified congressional committees of any failure to receive such report.

SECTION 1. SHORT TITLE. This Act may be cited as the ``HIPAA Recreational Injury Technical Correction Act''. SEC. 2. COVERAGE AMENDMENTS. (a) ERISA.--Section 702(a)(3) of the Employee Retirement Income Security Act of 1974 (29 U.S.C. 1182(a)(3)) is amended-- (1) by striking ``Construction.--For'' and inserting the following: ``Scope.-- ``(A) Waiting periods.--For''; and (2) by adding at the end the following: ``(B) Limitation on denial of benefits.-- Notwithstanding paragraph (2), a group health plan, or a health insurance issuer offering group health insurance coverage in connection with a group health plan, may not deny benefits otherwise provided under the plan or coverage for the treatment of an injury solely because such injury was sustained while engaged in any particular mode of transportation specified in the plan consisting of the use of a motorcycle, snowmobile, all-terrain vehicle, or other similar recreational vehicle or horseback riding. Nothing in this subparagraph shall be construed as-- ``(i) prohibiting any such plan or issuer from excluding from coverage injuries sustained while engaged in such mode of transportation, if engaging in such mode of transportation, or the particular vehicle itself, is illegal under applicable law, or ``(ii) affecting the determination of primary and secondary insurance or subrogation or reimbursement rights between insurance policies.''. (b) PHSA.--Section 2702(a)(3) of the Public Health Service Act (42 U.S.C. 300gg-1(a)(3)) is amended-- (1) by striking ``Construction.--For'' and inserting the following: ``Scope.-- ``(A) Waiting periods.--For''; and (2) by adding at the end the following: ``(B) Limitation on denial of benefits.-- Notwithstanding paragraph (2), a group health plan, or a health insurance issuer offering group health insurance coverage in connection with a group health plan, may not deny benefits otherwise provided under the plan or coverage for the treatment of an injury solely because such injury was sustained while engaged in any particular mode of transportation specified in the plan consisting of the use of a motorcycle, snowmobile, all-terrain vehicle, or other similar recreational vehicle or horseback riding. Nothing in this subparagraph shall be construed as-- ``(i) prohibiting any such plan or issuer from excluding from coverage injuries sustained while engaged in such mode of transportation, if engaging in such mode of transportation, or the particular vehicle itself, is illegal under applicable law, or ``(ii) affecting the determination of primary and secondary insurance or subrogation or reimbursement rights between insurance policies.''. (c) Internal Revenue Code.--Section 9802(a)(3) of the Internal Revenue Code of 1986 is amended-- (1) by striking ``Construction.--For'' and inserting the following: ``Scope.-- ``(A) Waiting periods.--For''; and (2) by adding at the end the following: ``(B) Limitation on denial of benefits.-- Notwithstanding paragraph (2), a group health plan may not deny benefits otherwise provided under the plan for the treatment of an injury solely because such injury was sustained while engaged in any particular mode of transportation specified in the plan consisting of the use of a motorcycle, snowmobile, all-terrain vehicle, or other similar recreational vehicle or horseback riding. Nothing in this subparagraph shall be construed as-- ``(i) prohibiting any such plan from excluding from coverage injuries sustained while engaged in such mode of transportation, if engaging in such mode of transportation, or the particular vehicle itself, is illegal under applicable law, or ``(ii) affecting the determination of primary and secondary insurance or subrogation or reimbursement rights between insurance policies.''. (d) Effective Date.--The amendments made by this section shall apply with respect to injuries occurring during plan years beginning after 90 days after the date of the enactment of this Act.

HIPAA Recreational Injury Technical Correction Act - Amends the Employee Retirement Income Security Act of 1974 (ERISA), the Public Health Service Act, and the Internal Revenue Code to prohibit a group health plan or health insurance issuer offering group health coverage from denying benefits or coverage otherwise provided under the plan for the treatment of an injury solely because it was sustained while a person was engaged in any particular mode of transportation specified in the plan, consisting of the use of a motorcycle, snowmobile, all-terrain vehicle, or other similar recreational vehicle or horseback riding, unless such mode of transportation or its use was illegal.

the finding of a renal mass on imaging is suggestive of metastatic non - small cell lung cancer in the presence of a lung tumor but can also have another origin . we describe the case of a patient diagnosed with stage iv lung cancer based on a renal metastasis . a second opinion including review of histopathological data and additional imaging followed by lung surgery and cryoablation of the kidney lesion revealed two tumors of different origins , non - small cell lung cancer and a renal cell carcinoma . the presence of a renal mass diagnosed on a ct scan in a patient with lung cancer is not always synonymous with metastatic disease . confirmation of diagnosis by tissue sampling is mandatory , especially if a synchronous primary tumor is possible . the presence of metastatic non - small cell lung cancer ( nsclc ) can be suspected by imaging . however , tissue sampling is required to confirm the diagnosis , especially if a synchronous primary tumor is possible . in this case report , we present a case with stage iv lung cancer based on a renal metastasis . a 48-year - old female received palliative radiotherapy ( 30 gy ) directed to vertebrae th9-th12 and 4 cycles of chemotherapy [ gemcitabin 1,200 mg / m ( on days 1 and 8) , carboplatin 80 mg / m ] for an 18-fdg - pet avid , thyroid transcription factor-1 ( ttf-1 ) positive adenocarcinoma of the right lower lobe invading the thoracic vertebrae 10 , and an additional 18-fdg - pet negative lesion in the right kidney , cytology - confirmed adenocarcinoma , considered as a distant metastasis ( ct4nxm1 ) . therapy resulted in a slight reduction of both lesions . due to the determined stage ( iv ) the patient 's data were reviewed and additional 18-fdg - pet and ct scans were performed . except for the presence of the lesion in the kidney , no signs of metastases were found . therefore , the initial diagnosis was reconsidered as two primary tumors : an adenocarcinoma of the lung , stage iiib ( ct4n0m0 ) and an adenocarcinoma of the right kidney ( ct1a ) . two cycles of neo - adjuvant chemotherapy ( cisplatinum 80 mg / m , pemetrexed 500 mg / m on days 1 and 21 ) were administered prior to lung surgery . surprisingly , no tumor was found in the right lower lobe perioperatively . a hemicorporectomy of th10 and a resection of the processus transversus of th10 and th11 were performed , followed by spine stabilization . with regard to the lesion of the right kidney , an expectative approach was agreed because of stable disease ( no growth ) , its localization ( in the mid pole of the kidney ) and small size ( 2.3 cm ) . eleven months later , cryoablation was ultimately performed because the patient insisted on removal of the tumor , which revealed a papillary renal cell carcinoma . this case report emphasizes the importance of differentiating a primary from metastatic disease when a renal mass is diagnosed on a ct scan in a patient with lung cancer . although metastases to the kidneys are very uncommon , differentiation between these two entities is crucial for further management and prognosis ( palliative approach vs. curative intent ) [ 1 , 2 ] . on ct scan , a solitary metastasis to the kidney is more likely to be found in patients with higher tumor stage of the nonrenal malignancy or when other viscera are also affected . usually , the metastasis is an asymptomatic , small , endophytic , and solid mass . the finding of a corresponding hotspot on fdg - pet scan is suggestive of a metastasis , even if it appears to be benign on ct . however , if the primary tumor is not fgd - avid , this might not be the case . the possibility of a primary renal neoplasm should also be considered , but with caution , since the low sensitivity of detection of fdg - pet scans . histology obtained by percutaneous biopsy confirms or strengthens the diagnosis in case of small masses and doubts about performing a nephrectomy . ttf-1 is a typical marker for adenocarcinoma in the lung , while negative in primary renal neoplasms , as illustrated in fig . patients with localized lung cancers may obtain long - term survival with surgery . in case of a primary renal neoplasm ,

backgroundthe finding of a renal mass on imaging is suggestive of metastatic non - small cell lung cancer in the presence of a lung tumor but can also have another origin.case reportwe describe the case of a patient diagnosed with stage iv lung cancer based on a renal metastasis . a second opinion including review of histopathological data and additional imaging followed by lung surgery and cryoablation of the kidney lesion revealed two tumors of different origins , non - small cell lung cancer and a renal cell carcinoma.discussionthe presence of a renal mass diagnosed on a ct scan in a patient with lung cancer is not always synonymous with metastatic disease . confirmation of diagnosis by tissue sampling is mandatory , especially if a synchronous primary tumor is possible .

the standard model of electroweak interactions predicts the existence of a phase transition inbetween a low temperature symmetry broken and a high temperature symmetric phase @xcite . its thermodynamic properties lead to cosmological consequences . one might hope that the baryon asymmetry can be generated at the electroweak phase transition , if the transition is of strong first order . for values of the zero temperature higgs - mass @xmath3 gev the phase transition is of first order @xcite . as the higgs - mass is increased further , the thermodynamic singularity at the electroweak phase transition weakens . it is even possible , that for large values of the higgs - mass the phase transition loses its nonanalytical structure and is described by a crossover @xcite . in the strict sense the electroweak phase transition would then cease to exist . the exact determination of the critical higgs - mass value @xmath4 , at which the first order electroweak phase transition changes from first order to a crossover is important in view of its implications for the standard model . another aspect of the electroweak theory is the non - vanishing magnetic screening mass . it controls the infrared behavior of the theory at high temperatures and influences the nature of the phase transition itself . this work is a continuation of earlier studies and for details on the formulation of the theory we refer to @xcite . here we recall the simulated @xmath5 action functional : @xmath6 the relationship of the dimensionless lattice couplings @xmath7 to the couplings of the @xmath8 @xmath9 gauge - higgs system can be found in @xcite . our simulation is performed at @xmath10 and at @xmath11 values @xmath12 and @xmath13 . the hopping parameter is varied across the phase transition . these @xmath14-values correspond to higgs - mass values of @xmath15 and @xmath16 gev , if the 1-loop parameter mapping of @xcite is used . for possible correction terms inducing small corrections to the here cited higgs - mass values we refer to a forthcoming publication . to illustrate the critical behavior as a function of @xmath14 , or the higgs - mass , we display in figure [ cv_max ] the maxima of the @xmath17-susceptibility , which is given by @xmath18 3.0 in -0.5 in cv_max cv_max.eps maxima of the @xmath17-susceptibility . we investigate lattice sizes ranging from @xmath19 up to @xmath20 . the labeling of the data in figure [ cv_max ] corresponds to the one used in figure [ l_im ] . the data at @xmath21 are consistent with a first order transition , the dotted line with slope @xmath22 in the figure . at @xmath23 and @xmath13 a crossover is observed , while at @xmath24 the behavior is almost critical , the solid scaling curve in figure [ chi ] . the determination of the critical higgs - mass value relies on the analysis of fisher or lee - yang zeroes @xcite in the crossover - region of the theory . the partition function @xmath25 is analytically continued into the complex plane as a function of the complex hopping parameter @xmath26 . denoting with @xmath27 the lowest zero of @xmath25 , i.e. the zero in @xmath26 with smallest length , we expect in the vicinity of the critical end - point the scaling law @xmath28 such a scaling behavior can also be observed for lee - yang zeroes in the high temperature phase of the ising model . our strategy to localize the end - point then is to determine the value of @xmath14 , at which the regular contribution @xmath29 to the scaling law vanishes : @xmath30 . in figure [ l_im ] we display @xmath31 vs. @xmath32 . the solid curves in figure [ l_im ] correspond to fits with the scaling law . 3.0 in -0.5 in l_im l_im.eps imaginary parts of the lowest zeroes of the partition function . in figure [ fitconst ] the constant @xmath33 is displayed as function of @xmath14 . the data are consistent with a linear dependence on @xmath14 and the fit results into @xmath34 , corresponding to a critical higgs - mass value of approximately @xmath35 gev . 3.0 in -0.5 in fitconst fitconst.eps the determination of @xmath36 . the w - boson mass is determined from the w - boson propagator in landau - gauge , @xmath37 . for a detailed discussion of the implementation of the landau - gauge on a lattice see @xcite and references therein . we investigate the w - boson propagator at @xmath24 , which is very close to the critical higgs - mass . simulations have been performed on a @xmath38 lattice . the propagators have been analyzed in the same way as discussed in @xcite . our results are shown in figure [ mass_w ] . 3.0 in -0.6 in mass_w mass_w.eps w - boson screening masses , calculated on a @xmath38 lattice at @xmath24 . the full curve describes the fit to the data . the dashed curve represents the result obtained from gap equations . in the high temperature phase the w - boson propagator stays constant . a fit to the data for @xmath39 , the full triangles in the figure , yields @xmath40 . it is worthwhile to note , that in pure su(2 ) gauge theory the magnetic screening mass has a value @xmath41 , the horizontal full and dotted lines in figure [ mass_w ] . in the symmetry broken phase the mass increases rapidly . in this region the data are very well described by the ansatz @xmath42 the fit to the full circles in the figure results into a value for the exponent @xmath43 of @xmath44 . we are now able to compare our results with predictions based on gap equations @xcite . using similar parameters in the gap equations as in our study we observe a qualitative agreement , the dashed curve in the figure . we have exploited the scaling behavior of partition function zeroes in the vicinity of the critical end - point in order to determine the critical higgs - mass @xmath4 . the electroweak phase transition looses its first order character at a higgs - mass value of about @xmath35 gev . close to the critical higgs - mass we have measured the w - boson propagator in landau gauge . w - boson screening masses remain constant in the high temperature symmetric phase and increase in the low temperature higgs phase . the agreement of these data with predictions based on gap equations is of qualitative nature .

we study the effective 3-d su(2 ) gauge - higgs model at finite temperature for higgs - masses in the range from @xmath0 gev up to @xmath1 gev . the first order electroweak phase transition weakens with increasing higgs - mass and terminates at a critical end - point . for higgs - mass values larger than about @xmath2 gev the thermodynamic signature of the transition is described by a crossover . close to this higgs - mass value we investigate the vector boson propagator in landau gauge . the calculated w - boson screening masses are compared with predictions based on gap equations . epsf.sty # 1 # 2 # 3 # 4 # 5

in nanostructured thin films , photogenerated charge carriers can access the surface more easily than in dense films and thus react more readily . however , the high surface area of these films has also been associated with enhanced recombination losses via surface states . we herein use transient absorption spectroscopy to compare the ultrafast charge carrier kinetics in dense and nanostructured tio2 films for its two most widely used polymorphs : anatase and rutile . we find that nanostructuring does not enhance recombination rates on ultrafast time scales , indicating that surface state mediated recombination is not a key loss pathway for either tio2 polymorph . rutile shows faster , and less intensity - dependent recombination than anatase , which we assign to its higher doping density . for both polymorphs , we conclude that bulk rather than surface recombination is the primary determinant of charge carrier lifetime .

nanostructured materials offer unprecedented opportunities for thermal management and energy conversion by enabling a wider range as well as better control of the thermal conductivity @xcite . interfaces are central to their performance since they are scattering centers for heat carriers whose spatial distribution can be set during fabrication and whose dispersion strength can be controlled by tailoring their physical properties @xcite . nevertheless , the full potential of this revolution is still to be seen because there is a gap between our fundamental understanding of heat flow across single and multiple interfaces and the outcome of experimental measurements @xcite . for instance , while many simulations predict an enhancement of thermal conductance when a thin layer is inserted at a well bonded interface @xcite , only one experiment backs up that prediction so far @xcite . other experiments reporting conductance enhancement attribute the increase to a strengthening of the bonds at the boundaries @xcite . thermal interface engineering can be critical to many technologies like integrated circuits @xcite , phase change memory @xcite or high power electronics @xcite . a systematic and microscopic understanding of the bridging properties of an interfacial layer would go a long way towards that goal . adding an intermediate layer to a well - bonded interface can enhance the conductance in two different ways . in the harmonic limit , the layer could act as an impedance matching waveguide ( fig . [ fig_intro]a ) that reduces phonon reflection by destructive interference , similar to an antireflection coating @xcite . such a complete quenching of reflection occurs at a single frequency where the layer thickness can function as a quarter wave plate . in the anharmonic regime on the other hand , the layer can act as a bridge that facilitates frequency up and down conversion and increases the chances of phonons crossing the interface @xcite ( fig . [ fig_intro]b ) . the contribution of each individual effect to the total enhancement has not been systematically explored on the same material system . neither is there a clear criterion to choose the properties of the layer to maximize the conductance . in a 1d harmonic crystal for instance , we have established that a conductance maximum occurs when the impedance of the layer is the geometric mean of the contact impedances @xcite , even in presence of incoherent interface scattering . this thumb - rule persists for all lengths except the extreme limit of a single atom , where the mean generates a resonance that lies beyond the cut - off frequency and the system is forced to choose an arithmetic mean instead . however , this result has not been extended to multiple dimensions and crystal structures . a similar gap exists when phonon - phonon interactions are included , where it was proposed that the maximum conductance happens when the layer s density of states ( dos ) maximizes its overlap with the contact doss . this argument leads to two different criteria to obtain the maximum : 1 ) choose the atomic mass of the layer close to the arithmetic mean of the contact masses @xcite and 2 ) choose the debye temperature of the layer as the geometric mean of the contact debye temperatures @xcite . this unresolved discrepancy once again reveals our lack of understanding of the role played by the inserted layer for a real multidimensional physical system with complex modes , symmetries , and scattering events . in this paper we compare the enhancement of conductance in the harmonic and anharmonic limits and demonstrate the dominant role of anharmonicity ( sec . [ secharvsanh ] ) . we show that adding an intermediate layer can go either way by increasing or decreasing the conductance when phonon transport is restricted to the harmonic regime ( sec . [ secharmonic ] ) . in this limit , the conservation of energy and momentum constrain the number of available transport channels , so the increase in average transmission per channel must compete with the loss in the number of transport channels . when anharmonicity is added ( sec . [ secanharmonic ] ) , phonon - phonon interaction relaxes the conservation constraints and decouples the boundaries . maximizing the conductance becomes equivalent to minimizing the sum of individual boundary resistances . for our particular system , where only mass changes are considered , we show that the maximum happens when the layer mass is close to the geometric mean of the contact masses . as explained earlier , this result would be expected for 1-d coherent phonon transport at a single frequency . the surprise however is that the geometric mean ends up winning even for a 3-d crystal with broad - band phonon transport across modes and polarizations , including anharmonic and diffusive interactions . we can hypothesize that a bridging layer can in fact be a matching layer if we compositionally grade it so each slice has an acoustic impedance that is the geometric mean of its immediate nearest neighbors . the tendency of the geometric mean to favor the lower impedance of the pair mathematically translates to an exponentially varying spatially dependent impedance , with an exponent set by the logarithm ratio of the two impedances at either end of the layer . interface thermal conductance or thermal boundary conductance is defined as the ratio between the heat flux crossing an interface over the temperature drop across it , @xmath1 . within the landauer formalism , the conductance between two contacts at thermal equilibrium can be expressed as @xcite @xmath2 where @xmath3 is the cross sectional area , @xmath4 is the phonon energy , @xmath5 is the bose - einstein distribution , @xmath6 is the boltzmann constant , @xmath7 is the number of available propagating channels , which we call modes , and @xmath8 is the average transmission per mode . in a bulk material , each mode is a 1d subband generated by a particular polarization and a transverse wavevector , which gives rise to a quantum of conductance @xcite . the factor @xmath9 represents the sum of all the possible transmissions between the modes on the left and right contacts . this factor can be calculated using non - equilibrium green s functions ( negf ) as @xmath10 , with @xmath11 the retarded green s function describing the propagation of phonon waves in the channel , and @xmath12 the broadening matrix for the left ( l ) and right ( r ) contacts @xcite . to compare the conductance from landauer formalism with that from non - equilibrium molecular dynamics ( nemd ) , we need to take the classical limit of the bose - einstein distribution ( eq . [ equgq ] with @xmath13 ) and we need to subtract the contact resistance ( appendix [ app_cr ] and fig . [ fig_deltagmaxvst_lj]b ) . this value should be the limit of the nemd conductance as temperature tends to zero . figure [ fig_g_har_vs_anh ] plots the harmonic and anharmonic thermal conductances @xmath14 across interfaces with an added intermediate bridging layer or junction , belonging to a face centered cubic ( fcc ) crystal structure in one case and diamond cubic ( dc ) in the other . the boundaries between adjacent materials are assumed to be perfectly abrupt and the thickness of the junction is taken to be @xmath15 conventional unit cells . for each system , we vary the atomic mass of the junction @xmath16 in between the contact atomic masses @xmath17 and @xmath18 . we assume that the crystal structure , lattice constant @xmath19 and interatomic force constants are invariant along the system , so we can isolate the effect of a change in atomic mass . some consequences of relaxing these assumptions are discussed at the end of each of the following sections . the conductance in the harmonic regime is calculated from landauer formalism in the classical limit using negf to obtain @xmath9 , while the conductance in the anharmonic regime is calculated from nemd . note that we report the conductance measured from the left to the right material including the contribution from the junction . thus , the abrupt interface conductance from nemd is larger than that of the bridged interface when the junction mass is equal to one of the contact masses . those conductance values from landauer formalism are equal because the calculations are harmonic . the details of the simulations are spelled out in appendix [ app_sim_details ] . amu and * d ) * @xmath20 amu ) . the dashed lines are fourth order polynomial functions that fit the nemd data.,title="fig:",width=325 ] amu and * d ) * @xmath20 amu ) . the dashed lines are fourth order polynomial functions that fit the nemd data.,title="fig:",width=325 ] figures [ fig_g_har_vs_anh]a and [ fig_g_har_vs_anh]b suggest that anharmonicity plays a key role in the relative enhancement of conductance from an abrupt ( superscript @xmath3 ) to a bridged ( superscript @xmath21 ) interface . the anharmonic simulations show a relative increase in conductance ( @xmath22 at @xmath23 k ) three times larger than that of the harmonic simulations ( @xmath24 at @xmath25 k ) . this difference can not be explained in terms of the usual linear increase of conductance with temperature shown by nemd simulations of abrupt interfaces ( fig . [ fig_deltagmaxvst_lj]a ) @xcite . in fact , the maximum conductance of bridged interfaces increases non linearly with temperature ( fig . [ fig_deltagmaxvst_lj]a ) , with a rapid growth at low temperatures . this suggests the existence of a mechanism that limits the conductance enhancement just in the harmonic regime . in section [ secharmonic ] , we explain that the limiting mechanism arises from the conservation of phonon energy and transverse momentum , which constrains the number of available transport channels across the interface . we also show that for certain crystal structures , this mechanism can even destroy the conductance enhancement of bridged interfaces over abrupt interfaces ( fig . [ fig_g_har_vs_anh]c ) . and maximum conductance of the bridged interface @xmath26 vs. temperature for a fcc crystal calculated from nemd . the rapid increase of @xmath26 at low @xmath27 highlights the important role of anharmonicity enhancing @xmath26 relative to @xmath28 . * b ) * temperature profile of the abrupt interface from nemd . this profile allows us to include the contact resistances into the nemd conductance ( eq . [ equglgmd ] ) , which shows excellent agreement with our landauer calculations @xmath29.,width=325 ] in the limit of zero temperature , the conductances calculated from landauer and nemd methods are in excellent agreement ( fig . [ fig_deltagmaxvst_lj]a ) . the landauer conductance is defined using the temperature drop between contacts at thermal equilibrium @xmath30 . therefore , it _ includes _ additional resistances at the contacts that arise from the implicit scattering assumed to bring the distribution of phonons back to equilibrium ( appendix [ app_cr ] ) . on the other hand , the nemd conductance is defined using the temperature drop right at the interface @xmath31 ( fig . [ fig_deltagmaxvst_lj]b ) , so it _ excludes _ the resistances at the contacts . those resistances cause the temperature drops at the boundaries of the heat baths ( fig . [ fig_deltagmaxvst_lj]b ) , where thermal equilibrium is enforced . when we include the contact resistances into the nemd conductance ( right hand side of eq . [ equglgmd ] ) , we get the landauer conductance @xmath32 figure [ fig_deltagmaxvst_lj]a shows an example of the excellent agreement of the two conductances once we account for the effects of the contact resistances . in the anharmonic regime , our simulations show that the conductance enhancement is maximum when the junction mass is close to the geometric mean of the contact masses @xmath33 ( figs . [ fig_g_har_vs_anh]b and [ fig_g_har_vs_anh]d ) . this result is a consequence of the boundary resistance being an increasing function of the mass ratio of the materials at either side of the boundary ( sec . [ secanharmonic ] ) . therefore , the sum of the boundary resistances is minimum when the ratio of the masses is equal ( @xmath34 ) . notably , this is a much more general result than an antireflection coating , which requires in addition a quarter wave plate to not just minimize but completely eliminate the sum of the boundary resistances through destructive interference , that only works at a single frequency for a homogeneous layer material . when phonons transit without interacting with each other , adding an intermediate layer does not necessarily increase the interfacial conductance ( fig . [ fig_g_har_vs_anh]c ) . to understand this result , we start by rewriting eq . [ equgq ] to highlight the role of phonon transmission vs. number of transport channels on the interfacial conductance . @xmath0 is related to the factor @xmath9 , which represents the sum over all the possible phonon transmissions between modes of the left contact , junction and right contact . due to the perfectly abrupt nature of the boundaries , the system is periodic in the transverse direction , so that successful transmissions must conserve the transverse wavevector ( @xmath35 ) . we rewrite @xmath9 to highlight the factors contributing to transport as @xmath36=m_ct_c , \label{equmctc}\ ] ] where @xmath35 varies over the transverse brillouin zone , the conserving modes @xmath37 counts the number of nonzero transmissions or transport channels across the interface , and @xmath38 is the average transmission over the conserving modes @xcite . using these definitions , we can rewrite the conductance as @xmath39 with the contribution to the conductance by the conserving modes @xmath40 given by @xmath41 and @xmath42 . to calculate @xmath37 numerically , we find the propagating modes of the bulk left contact ( @xmath43 ) , junction ( @xmath44 ) and right contact ( @xmath45 ) by calculating @xmath9 from negf for each homogeneous material , where @xmath46 for each mode and 0 otherwise . then , the conserving modes are computed from @xmath47 \label{equmc}\ ] ] note that @xmath37 is a concept similar in spirit to the diffuse mismatch model @xcite , since it depends only on the bulk properties of each individual material . also note that we are assuming that tunneling across the junction is negligible , which is reasonable for junctions larger than four atomic layers . this assumption allows us to consider only transmissions involving propagating channels of the junction . the relative enhancement in the conductance of a bridged ( superscript @xmath21 ) interface compared to that of an abrupt ( superscript @xmath3 ) interface depends on the interplay between increasing the transmission and decreasing the conserving modes . figure [ fig_interfacewithadesionlayer ] compares the relative change in conductance , conserving modes and transmission using @xmath48 \left[\frac{\langle t^b_c\rangle_\omega}{\langle t^a_{c}\rangle_\omega}\right],\ ] ] with @xmath49 for the abrupt interface defined analogous to eq . [ equmc ] , but the minimum is taken only over the contact modes . for the fcc crystal ( fig . [ fig_interfacewithadesionlayer]a ) , the increase in transmission is enough to counter balance the decrease in modes . however , for the dc crystal ( fig . [ fig_interfacewithadesionlayer]b ) , the decrease in modes dominates and pushes the conductance of the bridged interface below that of the abrupt interface . the interplay between transmission and modes is a competition between increasing the value of individual transmitting channels vs. decreasing the number of them . due to decreasing the `` mismatch '' at each boundary and decreasing the number of conserving modes ( due to a new restriction on the conservation of momentum coming from the intermediate material.,width=325 ] we can design an intermediate bridging layer at an abrupt interface to improve the impedance matching and increase the mode averaged transmission ; however , it is important to note that an added layer always decreases the number of modes available for transport . this is a consequence of the need to conserve phonon energy and transverse momentum in three materials instead of two , which implies taking the minimum over three quantities instead of two ( eq . [ equmc ] ) . the extra constraint is more noticeable around frequencies where @xmath50 . for instance , fig . [ fig_materialmodes]b shows a reduction of the conserving modes of the bridged interface relative to those of the abrupt interface around @xmath51 and @xmath52 rad /s . note that at low frequencies , the acoustic branches of the lightest material dominate the conserving modes and @xmath53 . thus , at low temperatures we expect @xmath54 for both crystal structures , fcc and dc , since @xmath55 . and decreases the number of available modes . we plot the cases in which @xmath40 is minimum : @xmath56 amu for fcc crystal and @xmath57 amu for the dc crystal.,title="fig:",width=325 ] and decreases the number of available modes . we plot the cases in which @xmath40 is minimum : @xmath56 amu for fcc crystal and @xmath57 amu for the dc crystal.,title="fig:",width=325 ] as long as the system remains periodic in the transverse direction , i.e. invariant lattice constant and perfectly abrupt boundaries between adjacent materials , the concepts developed in this manuscript apply . however , when the transverse symmetry assumption is relaxed , for example when the lattice constants are not the same or when there are random defects or interatomic mixing at the interface , phonons can change their momentum when they cross the interface . therefore , the conserving modes do not represent anymore the available transport channels or modes across the interface . the number of transport channels is intimately related to the properties of the individual boundaries between adjacent materials , like the degree of interatomic mixing . in that case , conservation of energy allows us to define an upper bound for @xmath9 @xcite , @xmath58 which can be used as a measure of the number of transport channels . similar to the conserving modes , the minimum of the modes always decreases when a junction is added to an abrupt interface , because we are taking the minimum of three quantities instead of two ( fig . [ fig_materialmodes ] ) . the conserving modes @xmath37 and minimum of the modes @xmath59 can be convenient starting points to look for junction materials that could enhance interfacial conductance . for instance , the combinations of materials that maximize @xmath37 or @xmath59 should be more amenable to increases in interfacial conductance . when phonons interact with each other during transport across the junction , for instance through anharmonic terms in the channel potential , they change their energy and momentum . this process relaxes the conservation constraints in the harmonic limit and decouples the system resistance as the sum of boundary resistances plus a junction resistance @xmath60 figs . [ fig_g_har_vs_anh]b and [ fig_g_har_vs_anh]d suggest that the maximum conductance , or minimum resistance , happens when the junction mass is close to the geometric mean of the contact masses . a similar result in terms of impedances was found for the analog one dimensional system , where phonon transport was elastic but incoherent @xcite . the key element behind the result was that each boundary resistance is an increasing function of the impedance ratio of the materials at either side of the boundary . thus , minimizing the sum of resistances requires equating the impedance ratios ( @xmath61 ) . inspired by this result , it is tempting to suggest that @xmath0 is a function of the mass ratio alone . unfortunately this is not true because heavier materials yield lower conductances due to their smaller cut off frequencies , which can be seen by rewriting eq . [ equgq ] as @xmath62 with @xmath63 the minimum cut off frequency of the contacts @xmath64 and @xmath65 although the boundary conductance is not a function of the mass ratio alone , the conductance over the frequency cut - off @xmath66 is . figure [ fig_avgmt]a shows that @xmath67 is only a function of the mass ratio for both the anharmonic and harmonic limits . the anharmonic data results from combining eq . [ equgq2 ] with the boundary conductance extracted from our nemd simulations . the data from the boundary between left contact and junction ( red triangles ) is a little larger than that from the boundary between junction and right boundary ( blue triangles ) because the temperature is greater at the left boundary . the harmonic data comes from the landauer conductance after we have subtracted the contact resistances ( appendix [ app_cr ] ) . if that is not the case , we obtain the dashed line in fig . [ fig_avgmt]a , which is bounded for unity mass ratio due to the resistances at the contacts . , plotted per conventional unit cell , is a function of the mass ratio for abrupt interfaces . * b ) * junction mass @xmath16 that leads to minimum resistance vs. right contact mass @xmath18 while keeping the left contact mass fixed . the mass follows closely the geometric mean of the contact masses.,width=325 ] replacing the boundary resistances ( @xmath68 ) from eq . [ equgq2 ] into eq . [ equsumr ] and using @xmath67 from landauer ( solid line in fig . [ fig_avgmt]a ) , we numerically find the junction mass that maximizes interfacial conductance as a function of the ratio of the contact masses ( solid line fig . [ fig_avgmt]b ) . the noise in the plot is caused by the interpolation error in @xmath67 . the fair agreement of this curve with the results from nemd simulations ( figs . [ fig_g_har_vs_anh]b and d ) suggests that the knowledge of the harmonic boundary conductance is enough to approximate the junction mass that maximizes the conductance . nevertheless , one of the reasons behind the discrepancy is the flattening of the curve around the peak ( figs . [ fig_g_har_vs_anh]b and d , appendix [ app_sim_details ] and fig . [ fig_maxg_mdvsnegf ] ) , which combined with the uncertainty of the nemd results produces a corresponding spread in the maximum . in fact , the large spread of the conductance maximum and its relative insensitivity around that point with changes of junction mass is quite convenient for engineering , as it widens our choice of bridging masses that yield an overall large conductance . the solid curve on fig . [ fig_avgmt]b follows closely the geometric mean of the contact masses ( dashed line ) due to the dominant dependance of @xmath0 on the mass ratio . the deviations from this mean arise from the dependence of g on the overall phonon cut - off frequency @xmath63 , which adds a more complicated mass dependence . we can better understand the trend of maximum conductance by minimizing eq . [ equsumr ] @xmath69}_{\text{term } \beta } = 0 . \label{equminr}\ ] ] to obtain eq . [ equminr ] we use @xmath70 , eq . [ equgq2 ] , @xmath71 , @xmath72 , @xmath73 the derivative of @xmath74 with respect to @xmath16 and we neglect @xmath75 . we also express the cut off frequencies of the junction @xmath76 and right contact @xmath77 in terms of the cut off frequency of the left contact ( @xmath78 , @xmath79 ) . this is possible because the materials are identical except for the atomic mass , so the dispersion is a copy of the same function expanded or contracted along the frequency axis . @xmath80 is the area of the conventional unit cell that converts the value of @xmath67 per conventional unit cell in fig . [ fig_avgmt]a to per meter squared . when the ratio between the contact masses is close to one , choosing the junction mass close to the geometric mean of the contact masses maximizes the conductance ( fig . [ fig_avgmt]b ) . in that case , @xmath81 , @xmath82 and eq . [ equminr ] reduces to the terms @xmath83 and @xmath84 . this expression is minimum when @xmath85 . as the ratio of the contact masses increases , the junction mass that maximizes the conductance remains close to the geometric mean . this happens because the deviation of the second term relative to the term @xmath83 , caused by @xmath86 , is balanced to some extent by the increase of @xmath87 on the first term ( note that @xmath73 is negative ) . to minimize the resistance , 1 ) we assume the boundary resistances are in series , 2 ) we show the boundary conductance is an increasing function of the mass ratio , and 3 ) we conclude that the minimum resistance happens when the mass ratios are equal . this strategy can be used beyond systems with perfect boundaries where only the mass is allowed to change . we expect the same minimization outcome , @xmath33 , when interatomic mixing is added at the boundaries . mixing can ether suppress @xcite or enhance @xcite each boundary conductance . either way , we still expect a similar increasing trend of @xmath67 with mass ratio dictated by the frequency minimum of the modes @xmath59 instead of the conserving modes @xmath37 @xcite . by analogy , if we only allow changes of the interatomic force constants by varying the @xmath88 parameter of the lennard - jones potential , we expect minimum resistance when @xmath89 . although the force constants and masses have opposite effects on the cut off frequency , we still expect @xmath67 to be an increasing function of the @xmath88 ratio . when we allow changes of both the masses and force constants , a similar analysis suggests that the minimum resistance happens when @xmath90 . further studies are necessary to confirm our hypotheses and to extend it to matrix versions of @xmath91 and @xmath88 for anisotropic systems . we expect further enhancement of the conductance between the contacts by stacking several intermediate thin layers whose atomic masses change in an exponential fashion . this result follows from choosing the mass of each layer as the geometric mean of the masses of the adjacent layers . each geometric mean choice minimizes the sum of the boundary resistances adjacent to a particular layer . a similar conjecture has been demonstrated for 1d incoherent systems @xcite . we study the enhancement of thermal conductance when a thin film layer or junction is inserted at an abrupt interface . our simulations show three times larger enhancement when the harmonic approximation is relaxed , which highlights the important role of phonon - phonon interactions in this transport process . in fact , in the harmonic limit , adding a junction to the abrupt interface does not necessarily enhance the conductance . the result depends on the interplay between 1 ) increasing the transmission by improving the `` matching '' of the contacts and 2 ) decreasing the number of available transport channels that conserve energy and transverse momentum . when anharmonicity kicks in , the conservation constraints are relaxed and the resistance of the system can be split into the sum of boundary resistances . the resistance is minimized when the junction mass is the geometric mean of the contact masses , which follows from the increasing trend of the boundary resistance with mass ratio . the strategy to find the maximum conductance can be used beyond systems with perfect interfaces where only mass is changing . we hypothesize that for a graded junction the geometric mean result generalizes to an exponential progression of masses that can push the enhancement beyond that of a single layer . this paper exemplifies the powerful combination of landauer and nemd to study the harmonic vs. the anharmonic contributions to thermal conductance . , j.z . and . are grateful for the support from nsf - career ( qmhp 1028883 ) and from nsf - idr ( cbet 1134311 ) . this work used the extreme science and engineering discovery environment ( xsede ) @xcite ( dmr130123 ) , which is supported by national science foundation grant number aci-1053575 . r.r and p.m.n . acknowledge the financial support of the air force office of scientific research ( grant no . fa9550 - 14 - 1 - 0395 ) . we calculate the thermal conductance between the left and right contacts of abrupt and bridged interfaces ( fig . [ fig_systems ] ) . for each system , the crystal structure , lattice constant @xmath19 and interatomic force constants are invariant . the boundaries between adjacent materials are perfectly abrupt . the junction is six conventional unit cells long and the junction atomic mass @xmath16 is varied between the contact atomic masses @xmath17 and @xmath18 . we simulate interfaces on fcc and dc crystal structures . for the dc interfaces , the interatomic force constants are calculated from the stillinger - weber interatomic potential for si @xcite . this potential describes the energy in terms of two and three body potentials and includes interactions up to the second - nearest neighbors . the equilibrium lattice constant for this structure is @xmath92 at @xmath25 k. the mass for the left contact is chosen as the silicon mass @xmath93 amu and the right contact mass is chosen as @xmath94 amu , which is close to the mass of germanium . the conductance for the abrupt interface calculated from landauer or harmonic negf in the classical limit is @xmath95 mw m@xmath96 k@xmath97 ( fig . [ fig_g_har_vs_anh]c ) . this value is in good agreement with reported conductance values @xmath98 mw m@xmath96 k@xmath97 at @xmath99 k @xcite and @xmath100 m@xmath96 k@xmath97 @xcite , which belong to abrupt interfaces with contact masses @xmath93 amu and @xmath101 amu . our value is smaller because of the heavier mass on the right contact , which reduces the available phonon spectrum for conduction . for the fcc interfaces , the interatomic force constants are calculated from the lennard - jones potential with parameters @xmath102 ev , @xmath103 , and a cutoff distance of @xmath104 . this potential includes interactions up to the fifth - nearest neighbors and is chosen to be identical to that used by english _ @xcite to have a point of reference for benchmarking . the equilibrium lattice constant for this structure is @xmath105 at @xmath25 k. the mass of the left contact is fixed to @xmath106 amu , while the mass of the right contact is varied from 40 amu to 240 amu . for fig . [ fig_g_har_vs_anh]a and b , fig . [ fig_deltagmaxvst_lj ] , fig [ fig_interfacewithadesionlayer]a and fig . [ fig_materialmodes]a , @xmath107 amu . for fig . [ fig_g_har_vs_anh]d , @xmath20 amu . from harmonic negf in the classical limit , the conductance for the abrupt interface is @xmath108 mw m@xmath96 k@xmath97 . this is in excellent agreement with the conductance from nemd at @xmath109 k including the contact resistances @xmath110 mw m@xmath96 k@xmath97 . for the negf simulations , we take advantage of the transverse symmetry of the systems . we calculate @xmath9 in transverse wave - vector space ( @xmath111 space ) to simplify the 3d problem into a sum of 1d independent problems the transverse brillouin zone was split into @xmath112 grid points for both the fcc and dc crystals . for the nemd simulations we use the lammps md simulator on a system with @xmath113 conventional unit cells and a time - step of 2 fs . we impose periodic boundary conditions over @xmath114 and @xmath115 directions and set the atomic layers at the two ends of the system as walls . heat is added to the system from the left edge and removed from the right edge using the langevin thermostat . the baths temperatures are set to @xmath116 with a time constant of 1.07 ps over blocks of 10 unit cells length . this setup for the thermostat is done to ensure sufficient phonon - phonon scattering that prevents size effects . on the computations at very low temperatures ( @xmath109 k ) , we test for size effects by changing the cross section to @xmath117 and @xmath118 . we also vary the length of the domain to 100 unit cells and decrease the thermostat time constant to 0.54 ps . no significant change in the thermal boundary conductance is noticed . to prevent changes of pressure as the temperature varies from affecting thermal transport at the interface , we account for the thermal expansion of the system . we perform equilibration runs under zero pressure at different temperatures using the isothermal - isobaric ensemble ( npt ) . the results are used to find the dependence of the lattice constant with temperature , which is fitted to a third order polynomial function : @xmath119 atoms are first equilibrated under the microcanonical ensemble ( nve ) for 4 ns . next , heat is added to the system for 10 ns to achieve steady state . then , the temperature is recorded for 6 ns to ensure a proper statistical average . from the temperature profile , we estimate the thermal boundary conductance dividing the heat flux over the temperature drop , which arises from a linear fit of the temperature at each lead extrapolated to the interface . most of the conductance values from nemd reported in this paper are averages over five independent calculations whose initial condition is generated randomly . the maximum conductances reported as asterisks on fig . [ fig_avgmt]b are the maximum of fourth order polynomial functions used to fit the nemd data . the discrepancy in fig . [ fig_avgmt]b between the maximum conductance of the bridged interface extracted from nemd and the one predicted from landauer can be attributed to the flattening of the @xmath0 vs. @xmath16 curve around the maximum . figure [ fig_maxg_mdvsnegf ] shows the region ( shaded area ) where the enhancement of conductance is within 5% of the maximum enhancement . in that region , it is difficult to pinpoint the exact location of the maximum due to the uncertainty of the nemd results nevertheless , the overall shapes of the landauer and nemd curves used to predict the maximum are in excellent agreement ( fig . [ fig_maxg_mdvsnegf ] ) . the different height between the curves is a consequence of the larger boundary conductances obtained with nemd simulations ( fig . [ fig_g_har_vs_anh]b ) . the landauer curve does not include the intrinsic resistance of the junction . thus , its similarity with the shape of the nemd curve in fig . [ fig_maxg_mdvsnegf ] suggests that individual boundaries play a dominant role in the maximization process . thus , the quality of the conductance enhancement depends mostly on our ability to decrease the sum of the boundary resistances . amu , * b ) * @xmath120 amu , * c ) * @xmath20 amu . the shaded area shows the masses whose nemd conductance enhancement is within 5% of the maximum enhancement . the landauer curves come from eq . [ equsumr]@xmath121 using @xmath67 from landauer ( solid line fig . [ fig_avgmt]b).,title="fig:",width=325 ] amu , * b ) * @xmath120 amu , * c ) * @xmath20 amu . the shaded area shows the masses whose nemd conductance enhancement is within 5% of the maximum enhancement . the landauer curves come from eq . [ equsumr]@xmath121 using @xmath67 from landauer ( solid line fig . [ fig_avgmt]b).,title="fig:",width=325 ] according to landauer theory , the conductance of a device in between two contacts at thermal equilibrium is defined by eq . [ equgq ] . when the device and the contacts are made of the same material , the transmission @xmath8 equals one . in that case , we get the upper limit of conductance , which is proportional to the quantum of conductance times the number of propagating channels @xcite . since @xmath122 , there can not be any resistance associated with the flow of phonons inside the device . therefore , the maximum conductance measures the resistance at the contacts . this resistance arises from the implicit scattering processes that have to happen at the contacts , to bring the flowing phonons back to an equilibrium distribution @xcite . the diffusive nature of those scattering processes allows us to split the resistance associated with the maximum conductance into the sum of the resistances at the contacts . since for a homogeneous material those resistances should be equal , we can define the contact conductance in the classical limit as @xmath123 with @xmath124 the cut off frequency of the material and @xmath125 the conductance from landauer theory @xmath126 is the parallel of the device conductance @xmath127 with the contact conductances @xmath128 and @xmath11 , so the device conductance is given by @xmath129 combining @xmath130 with eq . [ equgq2 ] we extract the @xmath67 referred as landauer-@xmath131 in fig . [ fig_avgmt]a . the method presented here is one way to approximate the contact resistances . other approximations have been presented , which include an analogy to the four probe measurements @xcite . from the temperature profile of the nemd simulations when @xmath132 ( fig . [ fig_deltagmaxvst_lj]b ) , we can estimate the contact resistances , which are related to the temperature drops at the edges of the heat baths . at the contacts or heat baths , every time step the velocities of the atoms are rescaled to a thermalized distribution , which emulates phonon - phonon scattering processes bringing the region back to equilibrium . everywhere else , phonons do not interact because the low temperature makes the system harmonic . therefore , once a phonon leave the contacts it can not relax its energy creating a non equilibrium distribution everywhere outside the bath regions . the temperature plotted in fig . [ fig_deltagmaxvst_lj]b is a representation of the total kinetic energy of the region with an equilibrium distribution . the conductance measured from nemd uses the temperature drop at the interface ( @xmath133 ) , while the one measured from landauer uses the temperature drop at the contacts ( @xmath134 ) . since the heat flux ( @xmath135 ) crossing the system is the same , we can relate the conductances from the two methods with eq . [ equglgmd ] . using this relation , we found excellent agreement between the results from landauer and nemd ( fig [ fig_deltagmaxvst_lj]a ) . another example supporting this relationship is shown in our recent work @xcite . 30ifxundefined [ 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 \doibase http://dx.doi.org/10.1063/1.1524305 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/s1748-0132(07)70018-x [ * * , ( ) ] link:\doibase 10.1007/s12274 - 010 - 1019-z [ * * , ( ) ] link:\doibase 10.1080/15567265.2015.1031857 [ * * , ( ) ] link:\doibase 10.1155/2013/682586 [ * * , ( ) ] \doibase http://dx.doi.org/10.1063/1.4832615 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/j.ijheatmasstransfer.2007.01.040 [ * * , ( ) ] http://stacks.iop.org/0953-8984/23/i=49/a=495303 [ * * , ( ) ] \doibase http://dx.doi.org/10.1016/j.ijheatmasstransfer.2012.02.019 [ * * , ( ) ] link:\doibase 10.1103/physrevb.85.035438 [ * * , ( ) ] link:\doibase 10.1103/physrevb.86.235304 [ * * , ( ) ] \doibase http://dx.doi.org/10.1063/1.4757941 [ * * , ( ) , http://dx.doi.org/10.1063/1.4757941 ] link:\doibase 10.1103/physrevb.92.144302 [ * * , ( ) ] link:\doibase 10.1103/physrevb.90.024301 [ * * , ( ) ] \doibase http://dx.doi.org/10.1063/1.4793431 [ * * , ( ) , http://dx.doi.org/10.1063/1.4793431 ] http://dx.doi.org/10.1038/nmat3465 [ * * , ( ) ] link:\doibase 10.1103/physrevapplied.5.014009 [ * * , ( ) ] link:\doibase 10.1109/led.2008.2003012 [ * * , ( ) ] \doibase http://dx.doi.org/10.1063/1.3437632 [ * * , ( ) , http://dx.doi.org/10.1063/1.3437632 ] \doibase http://dx.doi.org/10.1063/1.4893789 [ * * , ( ) ] \doibase http://dx.doi.org/10.1063/1.4710993 [ * * , ( ) ] http://www.worldcat.org/isbn/0521631459[__ ] , ed . 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we study the thermal conductance across solid - solid interfaces as the composition of an intermediate matching layer is varied . in absence of phonon - phonon interactions , an added layer can make the interfacial conductance increase or decrease depending on the interplay between ( 1 ) an increase in phonon transmission due to better bridging between the contacts , and ( 2 ) a decrease in the number of available conduction channels that must conserve their momenta transverse to the interface . when phonon - phonon interactions are included , the added layer is seen to aid conductance when the decrease in resistances at the contact - layer boundaries compensate for the additional layer resistance . for the particular systems explored in this work , the maximum conductance happens when the layer mass is close to the geometric mean of the contact masses . the surprising result , usually associated with coherent antireflection coatings , follows from a monotonic increase in the boundary resistance with the interface mass ratio . this geometric mean condition readily extends to a compositionally graded interfacial layer with an exponentially varying mass that generates the thermal equivalent of a broadband impedance matching network .

cygnus x-3 was discovered as a strong x - ray source by a rocket flight in 1966 ( giacconi et al . six years later in 1972 it was found to have a radio counterpart ( braes & miley 1972 ) . in that same year cyg x-3 underwent its first observed series of radio flares , attracting an intense radio monitoring campaign ( see gregory et al . 1972 et seq ) . during this period x - ray observations detected a 4.8 hour modulation in the signal from cyg x-3 ( parsignault et al . 1972 ; sanford & hawkins 1972 ) ; this was interpreted as being the orbital period of the system . a 12th mag infrared k - band counterpart was discovered using the radio position ( becklin et al . 1972 ) , and this was subsequently found to exhibit the same 4.8 hour modulation observed in x - rays ( becklin et al . 1973 ) , confirming the association between radio , ir and x - ray sources . in more recent years , as well as regular monitoring at cm wavelengths ( e.g. waltman et al . 1994 , 1995 ) , cyg x-3 has been observed at mm wavelengths ( baars et al . 1986 ; fender et al . 1995 ) , in the infrared between 0.9 - 4.8 @xmath1 m ( e.g. molnar 1988 , van kerkwijk et al . 1996 , fender et al . 1996 ) , and in the red - optical ( wagner et al . 1990 ) . in the visible band cyg x-3 remains undetected due to the high degree of interstellar absorption along the line of sight to the system ( @xmath2 mag : e.g. van kerkwijk 1996 ) at higher energies cyg x-3 is a bright x - ray source with luminosity states which seem to be correlated with radio activity ( watanabe et al . 1994 ) . in the high state the x - ray luminosity in cyg x-3 approaches , and possibly exceeds , the eddington limit for a solar mass object . cyg x-3 is also a strong source of @xmath0-rays , with claimed detections at up to pev energies ( see e.g. bonnet - bidaud & chardin 1988 ; protheroe 1994 for reviews ) . radio mapping observations have revealed the presence of a milliarcsecond - scale bipolar jet with an expansion velocity of @xmath3 c ( at 10 kpc ) following both giant- and small - flaring periods ( geldzahler et al . 1983 ; spencer et al . 1986 ; molnar , reid & grindlay 1988 ; schalinkski et al . 1995 ) as well as more extended structures on arcsecond- ( strom , van paradijs & van der klis 1989 ) and arcminute - scales ( wendker , higgs & landecker 1991 ) . since 1972 , of the order of 40 radio flare events have been observed in cyg x-3 , with peak flux densities ranging from 1 to 20 jy , in comparison with a quiescent level of 50 - 100 mjy at cm wavelengths ( e.g. waltman et al . 1994 , 1995 ) the autumn 1972 flare remains the event most extensively covered at radio wavelengths ( gregory et al . 1972 et seq ) and displays many properties typical of radio flaring periods in cyg x-3 . these include a tendency for shorter wavelength emission to peak earlier and higher than at longer wavelengths , and peak emission initially at @xmath4 cm but progressing gradually toward longer wavelengths throughout the series of flare events . the former point is as predicted for an expanding synchrotron - emitting cloud of relativistic electrons by van der laan ( 1966 ) . the latter point is harder to explain , and although it may be considered to be due to a general decrease of opacity at cm wavelengths in the local environment of the emitting electrons ( waltman et al . 1995 ) exactly what this interpretation really means is unclear . general consensus , however , for models of the radio flaring emission does involve a synchrotron - emitting cloud of electrons , probably associated with the radio jets , and with varying degrees ( and causes ) of local opacity and geometry ( e.g. gregory et al . 1972 ; marscher & brown 1975 ; mart , paredes & estalella 1992 - hereinafter mpe92 ) . observations in bands other than the radio during periods of radio flaring have been rare , though pomphrey & epstein ( 1972 ) and baars et al . ( 1986 ) have observed mm emission during active radio periods and found it to be roughly consistent with the synchrotron tail of the cm emission ( although baars et al . found the rise and decay times of flares at 3.3 & 1.3 mm to be much shorter than their cm counterparts ) ; and the strong - lined infrared spectrum reported in van kerkwijk et al . ( 1992 ) was obtained during the decay period of a 4 jy flare ( kitamoto et al . during the 1994 feb - mar flaring period cyg x-3 was monitored extensively at 2.0 cm with the ryle telescope at cambridge , and at 3.6 and 13.3 cm with the nrl - green bank interferometer . these observations are illustrated in fig 1 ; we consider there to have been five flare events during this period and we label these i - v. observations were also obtained in the infrared using ukirt , and at mm and sub - mm wavelengths using jcmt , both on mauna kea in hawaii . the ryle telescope ( jones 1991 ) has been used to monitor variable sources , primarily during gaps in the main observing programmes of the telescope , in addition to the coordinated observations which were specifically scheduled . during the period discussed here , the telescope operated at 15 ghz with a bandwidth of 350 mhz . the stokes parameters i+q were measured in all cases . data from each interferometer pair are collected , together with interleaved calibration observations of b2005 + 403 , a nearby quasar which is unresolved at all baselines in use here . the calibrations were used to correct for the instrumental phases of the system ; the amplitude scale was calibrated by nearby observations of 3c48 or 3c286 . atmospheric refractive - index fluctuations introduce phase errors which increase with baseline ; the time - scales of these are such that it is not possible to remove them by using the interleaved calibrator . the optimum procedure is to use only the shorter baselines , for which the phase uncertainties are small , except in the few cases where the flux is exceptionally low ( before major flares ) when it may be desirable to use all the available data . during the observations described here , the telescope was in its ` compact array ' mode with 5 aerials in a group having maximum baseline of about 100 m ; in practice nearly all data use only this set of baselines . once the instrumental phases have been removed , the data for all the baselines selected are added , producing the effect of a phased array . this vector sum is smoothed in time and its amplitude is taken as the flux of the source ( in the rare cases of very low flux density , this procedure overestimates the flux ; the in - phase component of the vector sum is used to give an unbiased estimate ) . typical day - to - day uncertainty in the flux - density scale is less than 3% rms . the noise level on a typical 5-minute average is less than 2 mjy rms . cyg x-3 has been observed by the nrl - gbi monitoring program on a daily basis since 1982 . the green bank interferomter ( gbi ) was operated by the national radio astronomy observatory for the naval research laboratory ( nrl ) and the us naval observatory through 1996 april 1 . in autumn 1989 , the national radio astronomy observatory installed cryogenic receivers on the green bank interferometer . since october 1989 , cyg x-3 and the calibration sources were observed for approximately ten minutes each , simultaneously at two frequencies , 2.25 and 8.3 ghz . the flux densities were measured on the 2.4 km baseline and are the average of the left - left and right - right circular polarizations . cyg x-3 was observed three to 15 times a day on two different gain codes to facilitate accurate measurements over a range of possible , and occasionally rapidly changing , flux densities from 100 mjy to almost 20 jy . a flux density calibration procedure similar to that reported in waltman et al . ( 1994,1995 ) was employed here . three secondary calibration sources ( b0237@xmath5233 , b1245@xmath5197 , and b1328 + 254 ) were used to produce flux densities for cyg x-3 and b2005 + 403 . the flux densities of b0237@xmath5233 , b1245@xmath5197 , and b1328 + 254 were determined using observations of b1328 + 307 ( 3c 286 ) . the flux density of 3c 286 was based on the scale of baars et al . ( 1977 ) , and the assumed values were 11.85 jy at 2.25 ghz and 5.27 jy at 8.3 ghz . the quiescent flux densities for cyg x-3 were calibrated using the four calibration sources listed above , weighted by the difference in time between the observations of cyg x-3 and calibrator sources observed within 24 hours of the cyg x-3 observation . however , during flares when cyg x-3 was observed almost continuously from 5 hours east to 5 hours west of the meridian , scans of cyg x-3 were paired with scans of 2005 + 403 in order to remove hour angle gain effects in the flux densities . these may exceed 20 per cent at 8.3 ghz . in this case , the meridian observation of 2005 + 403 was calibrated using the three calibrators above . then , paired scans with 2005 + 403 were used to calibrate cyg x-3 . errors in the gbi data are flux dependent : 4 mjy ( 2 ghz ) or 6 mjy ( 8 ghz ) for fluxes @xmath6 100 mjy , 15 mjy ( 2 ghz ) or 50 mjy ( 8 ghz ) for fluxes @xmath7 1 jy , and 75 mjy ( 2 ghz ) or 250 mjy ( 8 ghz ) for fluxes @xmath7 5 jy ( one sigma ) . following the observations of radio flaring activity in cygnus x-3 as observed in the green bank and ryle telescope data , target - of - opportunity observations were requested and made on two nights at the united kingdom infrared telescope ( ukirt ) . all observations were made using ircam2 , a 58 @xmath8 62 imaging array operating in the @xmath9 m wavelength range . on 1994 february 23 , less than five days after the onset of the first radio flare , observations were made twice each in the h ( 1.6 @xmath1 m ) and k ( 2.2 @xmath1 m ) bands with an integration time of 10 s and flux calibrated using hd136754 . on the following night a series of five observations in the k band were made , each with 15 s integration time and flux calibrated using hd162208 . the observations on both nights were made near the end of the shift as dawn approached , hence the larger than usual errors . the ukirt observations are summarised in table 1 ; there is approximately 25 sec between subsequent exposures on the same night . we obtained , over a three day period between the first and second major flares in the sequence , a series of ( sub)millimetre observations using the james clerk maxwell telescope ( jcmt ) . all observations were made using ukt14 , a photometer operating in the 0.45 - 2.0 mm wavelength range . on 1994 feb 26 we obtained a 3@xmath10 upper limit at 1.1 mm and shortly afterwards a 3.9@xmath10 detection of cyg x-3 at 0.8 mm . observations on the following two days at 0.45 mm provided initially a 3@xmath10 upper limit and then a 4.8@xmath10 detection . the detection at 0.45 mm is the first reported detections of cyg x-3 at this wavelength ; detection at 0.8 mm ( at a similar flux level ) has also only been reported once before ( tsutsumi et al .. 1996 ) . the jcmt observations are summarised in table 2 . .ukirt observations during 1994 feb march [ cols="^,^,^ " , ] table 3 clearly illustrates the decreasing time delay of peak emission at 13.3 cm relative to that at 3.6 cm in the sequence i v. there is a hint at times in the data set of a small time lag between emission at 2.0 cm and that at 3.6 cm , but this effect is marginal and no systematic trend is yet evident . hjellming , brown & blankenship ( 1974 ) found that for the 1972 september radio flares the decline after peaking could be well described during the initial few days by an exponential decay . however , these authors found that after @xmath11 days the decline in the radio was better fitted by a power - law decay of index @xmath12 . the exponential decay proved troublesome for those applying the simple van del laan ( 1966 ) model for an adiabatically expanding cloud of relativistic electrons , which predicts a power - law decay at all times . however we note here that recent modelling work ( canosa , fender & pooley , 1997 ) has shown that the integrated flux from an approaching and receding plasmon , each of which is decaying with a power - law form in its rest frame , can mimic an exponential decay . mpe92 have tackled the reported change from exponential to power - law decay in their model by invoking twin radio jets which expand in the lateral direction exponentially at first , and then linearly at later times . this reproduces well an initial exponential and subsequent power - law decay . in order to investigate the form of the decay of the radio flare events the entire radio data set was searched by eye to look for periods of relatively smooth flux decline . the least - squares fitting routine _ gnufit _ was then used to find a best fit to the decay using both exponential and power - laws . radio observations of cyg x-3 tend to show clearer variability at higher frequencies : this , coupled with @xmath13 times more intensive coverage by the ryle telescope during this period than at green bank , meant that there are considerably more clear decays fitted at 2.0 cm than at 3.6 or 13.3 cm . we fitted in total 9 clear decays at 13.3 cm , 12 at 3.6 cm and 27 at 2.0 cm . in general the goodness of fit was very similar for both the exponential and power - law decays , and it is difficult to confidently discriminate between them . there is no evidence in the data for a change from exponential to power - law decay of index @xmath12 after @xmath11 days , as reported by hjellming et al . ( 1974 ) ( though this would be hard to observe as the mean interflare interval was 4 - 5 days ) . we shall take the measured exponential decay constant , @xmath14 , below as being representative of the rate of decay at each wavelength . the mean values for @xmath14 are @xmath15 , @xmath16 & @xmath17 d at 2.0 , 3.6 & 13.3 cm respectively . although the uncertainties in the fits to the green bank data are large ( particularly at 3.6 cm ) , there remains strong evidence for consistently longer decay times at longer wavelengths . this is contrary to the simple model of van der laan 1966 , in which the sole energy loss mechanism is adiabatic expansion and the same decay rate is expected at all wavelengths . the jcmt ( sub)mm observations of cyg x-3 during 1994 feb - march reveal the source to be in a more active state than mm observations during a period of radio quiescence in 1993 ( fender et al . there appears to be a fresh injection of particles between the two observations on jd 2448410 , with a @xmath18 mjy detection at 0.8 mm coming less than 20 min after a @xmath19 upper limit of 40 mjy at 1.1 mm was established . a significant change in flux density at @xmath20 mm on a timescale of @xmath21 min implies a limiting size to the emitting region of @xmath22 cm . this probably places the emission near the base of the jet , well within the cm ` photospheres ' ( fender et al . 1995 , waltman et al . the detection of cyg x-3 at at flux density of @xmath23 mjy at 0.45 mm on jd 2449412 shows the source to be anomalously strong at this wavelength , where an extrapolation of the spectrum from 2.0 cm with spectral index -0.55 would have predicted a flux density of @xmath24 mjy . this high flux at 0.45 mm may have been a precursor to flare ii , which peaked less than 24 hr later . cyg x-3 was also anomalously bright in the infrared h & k bands , by at least a factor of two , during the radio flaring period . on jd 2440406 the flux density was seen to increase rapidly during the observations . this effect was strongest in the k band , resulting in a reddening of the source in ( h - k ) . this is similar to the effect seen during rapid infrared flaring ( e.g. fender et al .. 1996 ) , but given the rapid evolution of such events , the non - simultaneity of the h- and k - band measurements does not allow much information to be derived from this observations . also , the observations on jd 2449407 reveal the k - band flux density to be decreasing steadily on a timescale of @xmath25 min . combined with comparable flux densities observed on the previous night , this implies that some ongoing replenishment of the infrared - emitting material must be taking place . in the model of mpe92 , wavelength - dependent synchrotron and inverse compton ` radiation losses ' were not considered to be significant when compared to the adiabatic expansion losses suffered by the laterally expanding jet . however , there is strong evidence presented here that radiation losses are important . this evidence is in the form of repeated examples in the data set of more rapid flux density decays at shorter wavelengths ( section 3.3 ) . it is particularly important that two wavelengths on the optically thin branch of the synchrotron emission ( i.e. 3.6 cm & 2.0 cm ) consistently show different decay rates , as decays at 13.3 cm can be clouded by evolution of the opacity of the ejecta itself ( mpe92 find a turnover wavelength of @xmath4 cm between the optically thin and initially self - absorbing branches of the emitted spectrum ) . the same interpretation can be drawn from observing that @xmath26 decreases below the mean optically thin branch value of @xmath27 ( fig 1(c ) ) . at this point we will summarize the absorption and loss mechanisms which may affect the observed emission from a radio - emitting plasmon in an astrophysical environment . * synchrotron self absorption . * free - free absorption from thermal electrons either entrained in jet / plasmon or in surrounding environment ( e.g. wind ) . in the model of mpe92 , synchrotron self - absorption is not significant at _ any _ time for @xmath28 cm . free - free absorption by entrained thermal electrons could be occurring . free - free absorption by thermal electrons in a wind , as envisaged by fender et al .. ( 1995 ) to explain quiescent cm - mm emission , should not affect the larger flares studied here as by the time decay commences ( @xmath29 day ) the ejecta should have passed beyond the relevant radio ` photospheres ' ( and waltman et al .. 1997 have in addition shown that the photospheric radii used in fender et al .. 1995 may have been overestimates ) . furthermore , free - free effects would attenuate _ long - wavelength _ emission most strongly , producing the opposite effect to that observed here ; for this reason we do not consider these processes in the following analysis ( although they are undoubtedly important in detailed modelling of flares ) . * adiabatic expansion losses . * synchrotron losses . * inverse compton losses . * bremsstrahlung between relativistic electrons and ` thermal ' protons . * ionisation losses . adiabatic expansion losses produce wavelength - independent decays and were the only loss mechanism considered by van der laan ( 1966 ) . it seems beyond doubt that some plasmon expansion is occuring , so this process can not be ignored ( and is in fact the benchmark against which the significance of other processes can be tested ) . both synchrotron and inverse compton losses produce wavelength - dependent decays , with shorter - wavelength emission being attenuated most rapidly as a result of the higher energy electrons losing energy fastest . the crucial parameters for these two wavelength - dependent mechanisms are magnetic field and radiation field respectively . together , we refer to these processes as ` radiation losses ' , and as their signatures are clearly observed , we shall consider them in detail . the exact contribution from bremsstrahlung between the nonthermal electrons and thermal protons is unclear , but as ( a ) we are not attempting to model the thermal electron population and ( b ) these losses are wavelength independent anyhow , we will not consider this process . finally , ionisation losses are mildly wavelength - dependent but much less so than either of the ` radiation losses ' and anyhow we expect the environment of the plasmon to be effectively fully ionised , so again do not consider this process . therefore , while it is an oversimplification , we conclude that the most important processes to consider are adiabatic expansion , synchrotron and inverse compton losses . the evidence has already been presented for the significance of one of the latter two processes ; it remains to be seen which process is dominant , and over what timescale . following the work of mpe92 , we retain their jet geometry and formulation governing the evolution of the lateral expansion velocity , jet radius and hence magnetic field ( via conservation of magnetic flux ) with time . from this the relative contributions from adiabatic expansion losses and synchrotron losses can be calculated . we futher make an approximation to the radiation field and calculate the relative contribution of inverse compton losses . details of the equations governing the model are given in appendix a of fender ( 1995 ) . the model parameters to be fit are : * @xmath30 , the magnetic field at the base of the jet * @xmath31 , the time at which the lateral expansion changes from exponential to linear * @xmath32 , the time constant for the exponential expansion , related to the observed decay constant @xmath14 by @xmath33 ( where p is the electron energy index , 2.1 for an optically thin spectal index of -0.55 ) * @xmath34 & @xmath35 , the temperature and radius of the black - body being used to approximate the radiation field from the companion to the compact object . from the observed change from exponential to power - law decay in the 1972 flares , we take @xmath31 to be 4 days , as did mpe92 ( although there is no evidence for this in the data , it may still have occurred , at least for flares i iv , having been lost in the rise of the following flare ) . assuming radiation losses to be of least significance at 13.3 cm , we take the observed decay mean constant @xmath36 days at this wavelength and use it to derive a value for @xmath32 of 2.31 d. we note here that while mpe92 predict some self - absorption at 13.3 cm , the decay rate at this wavelength is fairly consistent in all measurements ( up to four days after flare peak in some cases ) whereas self - absorption is expected to be of little significance after @xmath37 days . infrared observations ( e.g. van kerkwijk et al . 1996 ) indicate that the companion to the compact object has an absolute magnitude in the near ir of @xmath38 . an approximation to such a luminous object can be made by taking a black - body of @xmath34 = 40 000 k and radius @xmath39 . note that although the radiation field from the companion star almost certainly comes from a far more extended region ( i.e. a bright stellar wind , particularly in the case of the companion being a wolf - rayet star ) , given the high ejection velocity of @xmath40 c , the approximation to a relatively small black - body should be adequate . we use @xmath41 g as fit to the data by mpe92 and also obtained from applying equipartition theory to the cyg x-3 radio jets by spencer et al . ( 1986 ) ( we note however that there are no _ a priori _ reasons for energy equipartition to be a valid assumption - see e.g. leahy 1991 ) . using the above parameters , we find that inverse compton losses dominate the loss mechanisms for the first two days of jet expansion , and after this time remain important at between 10 50 % of the level of the expansion losses , which dominate from this point onwards . the exact proportion of the contribution from radiation losses is wavelength dependent , being most important at shorter wavelengths . fig 3 plots @xmath42 ( the inverse of the electron lifetime - this is proportional to the number of electons of energy e lost and is therefore a measure of the relative importance of each loss mechanism ) against time for this model . synchrotron losses do not play a major role , although increasing @xmath30 to 1.0 g is sufficient to make them important ( fig 4 ) . this is not an unphysical field and synchrotron losses should be considered in future models of radio emission from cyg x-3 . several authors dispute the high - mass , luminous nature of the companion star to cyg x-3 , preferring a low - mass x - ray binary ( or similar ) scenario . the relative contributions of the three loss mechanisms in such a scenario ( where we represent the companion star in this case by @xmath43 r@xmath44 , @xmath45 k ) are illustrated in fig 5 . given that radiation losses _ are _ observed , then if the lmxrb scenario is correct b@xmath46 g. we have found here that in adopting the geometry of mpe92 whilst including a massive luminous companion star , inverse compton losses dominate for @xmath7 the first two days after injection . this is inconsistent with the model fits put forward by mpe92 and in turn casts some doubt upon their fits and geometry . however , it should be noted here that inverse compton losses are the most geometry - independent of the loss mechanisms considered here and are not strongly affected by small changes in assumed jet configuration . in particular , a model was run for constant lateral expansion immediately after injection ( i.e. no period of exponential lateral expansion ) again inverse compton losses dominated over adiabatic and synchrotron losses when a highly luminous companion was considered . we should note here that the mpe92 model fits were for the more luminous 1972 radio flare which may have had different outflow / expansion parameters than the weaker events under discussion here . in the inverse compton process , electrons of energy @xmath47 will scatter photons of frequency @xmath48 to a mean frequency of @xmath49 ( e.g. hughes & miller 1991 ) . electrons radiating synchrotron emission at 2.0 cm at the base of the jet ( i.e. where we assume b=0.1 g ) will have energies of @xmath50 gev and hence lorentz factors @xmath51 . thus inverse compton losses suffered by these electrons will cause photons in frequency range @xmath52 hz ( i.e. infrared through uv , where emission from the luminous companion should be concentrated ) to be re - emitted after interaction with the electrons in the frequency range @xmath53 hz ( i.e. 20 kev - 2 mev ) : hard x - rays through @xmath0-rays . based upon this , and the observed importance of radiation losses , probably inverse compton , at 2.0 cm , we predict hard x - ray/@xmath0-ray bursts associated with radio flares . there may also be some constant contribution to the hard x - ray/@xmath0-ray flux from the inverse compton mechanism if the jet is continuous , but with a lower injection rate , during quiescence . given the clear trends , in particular the decreasing opacity , observed during the flaring sequence , we have attempted to construct a testable scenario for the evolution of the outburst . our favoured scenario is based upon a mass transfer ( mass loss ) instability , although other scenarios are considered . in this scenario we consider that events i - v ( or at least i - iv ) are as a result of separate injection events , and that the evolving characteristics reflect changing condition in the region of injection . the scenario is envisaged as follows , and illustrated in fig 6 . * stage 1 : initially cyg x-3 is in a quiescent state , with a low - level jet responsible for the quiescent radio emission . * stage 2 : a period of increased mass - loss from the companion star results in an increasing density of thermal electrons in the region of the accreting compact object . this causes the quenching of the jet ( exact mechanism unclear ) and thus radio emission is reduced . at the same time the infrared flux ( proportional to @xmath54 where @xmath55 & @xmath56 are the electron and ion number densities ) increases due to the higher electron and ion number densities , as does the x - ray flux , due to a higher accretion rate . * stage 3 : radiation and/or magnetic pressure builds up in the inner regions of the disc ( the exact mechanisms for producing jets remain unclear ) and finally there is an explosive injection of relativistic particles into the jet . this produces a radio flare , with considerable associated opacity due to a high proportion of absorbing thermal particles entrained in the jet . * stage 4 : subsequently the mass - loss rate from the companion star subsides towards its normal levels and a sucession of injections with decreasing proportions of associated absorbing thermal electrons occur . during this period the infrared and x - ray brightness begin to decline toward their normal levels ( although there may still be x - ray/@xmath0-ray flares due to inverse compton losses from later flares ) . eventually the source returns to quiescence c.f . stage 1 . flare v is anomalous and may be due to an interaction between the ejecta and part of the ism . if not , then it would appear that the rate of injection of relativistic particles into the jet had declined dramatically by the time this event occurred , resulting in a much longer rise time . this scenario has a lot of attractions in that it seems to explain the observed evolution of the opacity in the sequence i v , * plus * the strong infrared brightness and observed correlation between radio flares and bright x - ray states ( watanabe et al . it is also consistent with the suggestion from the infrared and ( sub)mm data that continued injections were taking place _ at least _ between flares i & ii . in attempting to explain the decreasing opacity during the flare sequence several other possible scenarios were considered , in particular one in which the flare events were recombination shocks occuring at increasingly large distances along the jet , and hence away from a source of opacity ( the stellar wind from the companion ) . there is evidence for such shocks causing _ in situ _ acceleration of particles in the jets of agn . however the assumed wind geometry ( c.f . fender et al . 1995 ) and jet velocity ( 0.3 c , c.f . schalinski et al 1995 ) are inconsistent with the rather slow evolution of the opacity in this scenario . furthermore the multiple - shock scenario is clearly inconsistent with our conclusion that inverse compton losses are the dominant radiation loss mechanism , and would require the ejecta to maintain a high magnetic field ( @xmath20 g ) and lose energy via synchrotron losses . if cyg x-3 turns out to have a low - mass companion , as proposed by several authors ( e.g. white & holt 1982 ; mitra 1996 ) then it seems unlikely that a mass - transfer rate instability could cause the oubursts . such instabilities are most likely in systems in which accretion via a stellar wind is dominant . in a low - mass , roche - lobe overflowing scenario then it may be that disc instabilities , such as those proposed to account for x - ray transient events , are responsible for the outbursts . we present detailed observations of an outburst from the enigmatic and poorly - understood x - ray binary cyg x-3 , revealing new phenomena and helping to clarify the intrepretation of previous observations across a broad wavelength range . we report for the first time confirmation of strongly quenched radio emission prior to outburst , independent of observations at green bank ( waltman et al . 1994 , 1995 ) . the quenched period , lasting @xmath57 days in the outburst reported here , is clearly an important period when the physical conditions local to the base of the jet / accretion disc region have changed significantly . whether the quenching is due to changes in the accretion disc or to physical quenching by circumstellar material is unclear , and further study of this phase is undoubtedly important . detailed observation and measurement of characteristic decay times at three wavelengths reveal conclusive evidence for wavelength dependence . measurements at 3.6 & 2.0 cm are particularly significant as these lie on the optically thin tail of the synchrotron emission and self - absorption does not have to be taken into account ( as it does in most cases at 13.3 cm ) . we fail to confirm the transition from exponential to power - law decay after @xmath11 days reported by hjellming et al . ( 1974 ) , although this may have occurred and been lost in the rise of a subsequent flare . the clearest interpretation of wavelength - dependent characteristic decay times is that radiation losses are important processes in the cyg x-3 jet . the same conclusion was drawn by baars et al . ( 1986 ) and fender et al . ( 1995 ) based upon comparison of mm and cm observations , and is consistent with the rapid fluctuations we have observed at ( sub)mm wavelengths during the outburst . in order to investigate this phenonemon we have calculated ( wavelength - dependent ) synchrotron and inverse compton losses as well as ( wavelength - independent ) adiabatic expansion losses using the geometry of mpe92 . we find that in the presence of a strong radiation field such as that from a luminous companion star , inverse compton processes are the dominant loss mechanism for the first @xmath58 days after injection of particles into the jet . without a luminous companion , as in a lmxrb scenario , a magnetic field of at least 1.0 g is required at the base of the jet . the opacity in the radio emitting region ( assumed to be the jet ) , as measured both by spectral indexes and time lags between emission at 3.6 & 13.3 cm , is observed to be anomalously high at the beginning of the flare sequence , declining gradually toward quiescence through the sequence of flares i - v. waltman et al . ( 1995 ) have found that the highest opacity occurs immediately following quenching , consistent with the very high opacity in flare i which occured less than 24 hr after the last observed quenched fluxes . the apparent build - up of opacity during quenching is suggestive of an increase in absorbing thermal electrons in the vicinity of the radio emission , possibly as a result of an enhanced density of the stellar wind from the companion star . combining our investigations into the nature of cyg x-3 outbursts with ideas presented in kitamoto et al . ( 1994 ) , watanabe et al . ( 1994 ) and waltman et al . ( 1995 ) , we have constructed a qualitative model for the evolution of an outburst in cyg x-3 . we propose that the heightened opacity in the radio emission is due to an enhanced proportion of entrained absorbing thermal electrons , as a result of an increase in density of the stellar wind from the companion star . the build up of opacity ceases at the last point of quenched emission and we observe a sequence of radio flares as the system seeks to rid itself of the build up of matter , possibly in the accretion disc . during the entire period the accretion disc has been bright and the source is in its high and soft state ( higher accretion rate plus more scattering ) . radio flares may be accompanied by hard x - ray/@xmath0-ray bursts as infrared and optical photons are upscattered to higher energies via inverse compton processes . the bright but declining infrared state of cyg x-3 as observed during the outburst is in agreement with this model , though we can not discriminate on the basis of our observations between possible contributions from a bright accretion disc and an enhanced stellar wind . further multiwavelength observations of cyg x-3 in outburst are clearly required to test and refine this scenario . we would like to thank josep mart for many useful comments and discussions relating to this work , the observers at ukirt and jcmt for giving up time to make observations at short notice , and mark garlick for proof - reading an early draft . rpf would like to thank the open university for a research studentship during the period of this research . radio astronomy at the naval research laboratory is supported by the office of naval research . the ryle telescope is funded by the uk particle physics and astronomy research council ( pparc ) . the ukirt is operated by the observatories on behalf of pparc . the jcmt is operated by the observatories on behalf of pparc , the netherlands organisation for scientific research , and the national research council of canada . this research made use of the simbad database , operated at cds , strasbourg , france . canosa t. , fender r. p. , pooley g. g. , in spencer r.e . , newell s.j . , eds , proc of the jodrell bank workshop ` relativistic jets from galactic sources ' , vistas in astronomy , vol 41 , number 1 , 1997 , in press

we present multiwavelength observations of cygnus x-3 during an extended outburst in 1994 february - march . intensive radio monitoring at 13.3 , 3.6 & 2.0 cm is complemented by observations at ( sub)millimetre and infrared wavelengths , which find cyg x-3 to be unusually bright and variable , and include the first reported detection of the source at 0.45 mm . we report the first confirmation of quenched radio emission prior to radio flaring independent of observations at green bank . the observations reveal evidence for wavelength - dependent radiation losses and gradually decreasing opacity in the environment of the radio jet . we find that the radiation losses are likely to be predominantly inverse compton losses experienced by the radio - emitting electrons in the strong radiation field of a luminous companion to the compact object . we interpret the decreasing opacity during the flare sequence as resulting from a decreasing proportion of thermal electrons entrained in the jet , reflecting a decreasing density in the region of jet formation . we present , drawing in part on the work of other authors , a model based upon mass - transfer rate instability predicting @xmath0-ray , x - ray , infrared and radio trends during a radio flaring sequence . binaries : close - stars : individual : cyg x-3 - radio continuum : stars

The pressure was on at Hofstra Tuesday night as President Barack Obama and Mitt Romney faced off for their second debate. With Obama urgently needing to make up for a lackluster performance during the first debate and Romney looking to fend off a fusillade of attacks that didn’t come his way last time, the truth sometimes got caught in the crossfire. Text Size - + reset Presidential debate post-analysis on POLITICO LIVE Debate results & takeaways on POLITICO LIVE (Also on POLITICO: Who won the debate?) Here’s POLITICO’s take on how closely the candidates hewed to the facts during their town hall-style showdown: Terrorism in Libya Obama: “I said that this was an act of terror.” While Romney insisted Obama never made this statement, on the day after the Benghazi attack, the president did strongly suggest it was a terrorist strike. But he didn’t say outright that the Benghazi attack was an act of terrorism. “No acts of terror will ever shake the resolve of this great nation, alter that character, or eclipse the light of the values that we stand for,” Obama said in a Rose Garden statement about the death of U.S. Ambassador to Libya Chris Stevens and three other Americans. (Also on POLITICO: Crowley calls Libya for Obama) The ambiguity there has given Romney and his supporters something to latch onto — they say the president was talking broadly, and not about the Benghazi attack specifically. And in the days that followed, the White House seemed reluctant to call it a terrorist attack. On Sept. 16, U.S. Ambassador to the U.N. Susan Rice went on several TV talk shows and declared that the U.S. government’s preliminary assessment was that the violence sprang from a “spontaneous” demonstration related to an anti-Muslim video. Director of National Intelligence James Clapper has said that Rice’s account was based on the initial take of U.S. intelligence agencies. They subsequently changed their view and now assess the incident as a pre-planned terrorist attack. (Also on POLITICO: 10 best debate lines from Romney, Obama) Romney’s tax plan Obama: “Look, the cost of lowering rates for everybody across the board 20 percent, along with what he also wants to do in terms of eliminating the estate tax, along what he wants to do in terms of corporates changes in the Tax Code — it costs about $5 trillion. Gov. Romney then also wants to spend $2 trillion on additional military programs, even though the military’s not asking for them. That’s $7 trillion. He also wants to continue the Bush tax cuts for the wealthiest Americans. That’s another trillion dollars. That’s $8 trillion.” Obama’s math overshot by about $1 trillion, by most estimates. The president said Romney’s budget plan would cost $8 trillion — $5 trillion in tax cuts, $2 trillion in additional military spending and $1 trillion from the extension of the Bush tax cuts for the wealthiest Americans. Romney’s tax plan is estimated to cost $5 trillion — including the cost of extending the Bush tax cuts. (PHOTOS: The in-your-face debate) Romney says that he would offset the cost of those tax cuts, in part by eliminating or scaling back taxpayer’s ability to take credits and deductions. He has not given full details, but again floated the idea of a $25,000 cap on deductions, as he did in the first debate. Before that, he had discussed a $17,000 cap. ||||| ABCNEWS.com ABC News' political team revisit the claims made by President Obama and Mitt Romney in last night's debate at Hofstra University. (Read the Full Transcript of the Second Presidential Debate and ABC News' Debate Analysis) Romney and Arizona's Immigration Law OBAMA: He called the Arizona law a model for the nation. ... ROMNEY: I did not say that the Arizona law was a model for the nation in that aspect. I said that the E-Verify portion of the Arizona law, which is -- which is the portion of the law which says that employers could be able to determine whether someone is here illegally or not illegally, that that was a model for the nation. ABC's Chris Good reports: As Romney said, he did not call Arizona's controversial SB-1070 law a "model." In CNN's Feb. 22 Republican primary debate in Mesa, Ariz., moderator John King asked Romney about immigration. "What about arresting? Should there be aggressive, seek them out, find them and arrest them as the Sheriff Arpaio advocates?" King asked. Romney's response: "I think you see a model in Arizona. They passed a law here that says -- that says that people who come here and try and find work, that the employer is required to look them up on E-Verify. This e-verify system allows employers in Arizona to know who's here legally and who's not here legally." Although media outlets and fact checkers have pointed out that Romney was talking about E-Verify, that hasn't stopped Democrats from repeating this talking point against him. Obama made another claim that Romney's top adviser on immigration designed the SB1070 law. "His top adviser on immigration is the guy who designed the Arizona law, the entirety of it; not E-Verify, the whole thing," the president said. An informal Romney adviser, Kris Kobach, helped draft the SB-1070 law and filed a suit to stop Obama's administrative action. In September, Romney told Univision he had not met with Kobach. "He may well be part of a policy team," Romney said. "I have not met with him yet. And don't know whether he is or he is not." In April, the campaign described Kobach as a "supporter" rather than an advisor to Politico's Glenn Thrush, but Kobach then told ThinkProgress he was communicating regularly with senior Romney advisers. Kobach was still "providing advice on immigration policy," he told ThinkProgress. "I don't want to go into great detail, but I communicate regularly with senior members of Romney's team." Does Obama's Pension Have Money in the Cayman Islands? During one exchange tonight Romney stated that President Obama's pension had investments in China and the Cayman Islands. ROMNEY: Just going to make a point. Any investments I have over the last eight years have been managed by a blind trust. And I understand they do include investments outside the United States, including in -- in Chinese companies. Mr. President, have you looked at your pension? Have you looked at your pension? OBAMA: I've got to say... ROMNEY: Mr. President, have you looked at your pension? OBAMA: You know, I -- I don't look at my pension. It's not as big as yours so it doesn't take as long. ROMNEY: Well, let me give you some advice. OBAMA: I don't check it that often. ROMNEY: Let me give you some advice. Look at your pension. You also have investments in Chinese companies. You also have investments outside the United States. You also have investments through a Cayman's trust. ABC News' Luis Martinez and Jason Ryan have the facts: Gov. Romney is referring to President Obama's pension with the state of Illinois during his time served as a State Senator. Under Agreements or Arrangements President Obama's Dec. 2011 Public Financial Disclosure Report for the Office of Government Ethics lists the General Assembly Defined Benefit Pension Plan as the only holding under this category. It says "no further contributions by former employer," funding began in 1997. The pension is managed by the General Assembly Retirement System, State of Illinois. The main site for the fund's reports is HERE The FY 2013 First Quarter Purchase and Sales Report mentions holdings in Chinese companies among the pension fund's numerous investments. The Romney campaign says the Obama Illinois Pension fund has numerous private equity investments, including one domiciled in the Cayman Islands, the Advent International Group VI-A. An independent search for this fund turned up this filing with the Securities and Exchange Commission for an investment opportunity by this fund. It lists the Advent International GPE VI Limited Partnership as being organized in the Cayman Islands. Other filings only list this particular fund's Executive offices as being listed in Boston, Mass. Both Candidates Say They'll Grow Pell Grants ROMNEY: "I want to keep our Pell grant program growing and our loan program so that people are able to afford school." Romney's own education proposal, known as a "Chance for Every Child," would "[refocus] Pell Grant dollars on the students that need them most and place the program on a responsible long-term path that avoids future funding cliffs and last-minute funding patches." During a "Meet the Candidates" forum on Univision, Romney elaborated that he does not fully support all of Ryan's proposals for changes to Pell Grants, especially freezing the current rate. "The Republican budget called for a Pell Grants being capped out at their current high level. My inclination would be to have them go with the rate of inflation," Romney said Sept. 19. "It's important in higher education that we get serious about the fact that the inflation of tuition has been much faster than inflation generally. And my view is we have to hold down the rate of tuition increases and fee increases in higher education." If you buy Romney's claim that he has his own ideas for Pell Grants other than Ryan's proposals, it seems hard to disprove that he wants to keep it growing. OBAMA: "We've expanded Pell Grants for millions of people, including millions of young women, all across the country. We did it by taking $60 billion that was going to banks and lenders as middlemen for the student loan program, and we said, let's just cut out the middleman. Let's give the money directly to students. And as a consequence, we've seen millions of young people be able to afford college, and that's going to make sure that young women are going to be able to compete in that marketplace." Current law signed by President Obama sets the maximum grant at $5,645 in 2013 and $6,030 by 2017, enjoying increases based on inflation. About 9 million students receive Pell Grants, the biggest chunk of financial aid from the federal government. It has already grown about $900 since Obama took office. Republicans point to a government study that suggests the increase of Pell Grants has artificially driven up the price of tuition. Tuitions and fees for four-year public colleges increased 72 percent above inflation over the past decade, averaging $8,244 last year, according to the College Board, which represents more than 6,000 schools. Student loan debt in the U.S. is above $914 billion while the average borrower owes more than $24,000, the Federal Reserve Bank of New York says, according to the Associated Press. Most criticism of Romney's education proposals are tied to his presumed support of the Ryan Budget, which would reduce Pell Grants by increasing eligibility requirements and freezing the maximum grant at its current value of $5,550 according to the Center on Budget and Policy Priorities. It also rescinds mandatory spending for Pell Grants and shifts the costs to annual appropriations bills. The Center on Budget and Policy Priorities found in a study that the Ryan budget's reforms were applied across the board, it would result in a $161 billion budget deficit, while the president's budget proposal would fall only $52 billion short. Did Obama Call Libya Attack 'Terror' in the Rose Garden on Sept. 12? OBAMA: The day after the (Benghazi) attack I stood in the Rose Garden and I told the American people and the world that we are going to find out exactly what happened. That this was an act of terror and I also said we are going to hunt down those who committed this crime. ROMNEY: I think it's interesting that the President just said something which is that one the day after the attack, he went in the Rose garden and said this was an act of terror. (Obama nods) OBAMA (off-mike): That's what I said. ROMNEY: You said in the Rose Garden the day after the attack it was "an act of terror?" It was not a spontaneous demonstration. Obama: Please proceed. ROMNEY: Is that what you're saying? I want to make sure we get that for the record because it took the President 14 days before he called the attack in Benghazi an act of terror. OBAMA: Get the transcript. CROWLEY: He did in fact, sir ABC's Dana Hughes has the facts: Moderator Candy Crowley is right that Obama called the attack "act of terror" on Sept. 12th, the day after the attack. "No acts of terror will ever shake the resolve of this great nation, alter that character, or eclipse the light of the values that we stand for. Today we mourn four more Americans who represent the very best of the United States of America. We will not waver in our commitment to see that justice is done for this terrible act. And make no mistake, justice will be done," said the President that day. BUT - and there's a big but. Romney is right in that administration officials continued to say the attack was spontaneous, and came from a protest and it was White House Press Secretary Jay Carney who said the president considered it a terror attack on Sept. 26, 14 days later. A reporter asked Carney about the president's assessment between Sept. 12 and Sept. 26. "Is there any reason why the president did not - he was asked point-blank in 'The View' interview, is this a terrorist attack, yes or no? Is there any reason he didn't say 'yes'?" "He answered the question that was asked, and there's no reason that he chose the words he did beyond trying to provide a full explanation of his views and his assessment that we need to await further information that the investigation will uncover," said Carney. "But it is certainly the case that it is our view as an administration, the president's view, that is was a terrorist attack." Monday, Secretary of State Hillary Clinton accepted the blame for the Libya attack. Obama contradicted that at the debate Tuesday. Candidates Spar on Oil and Natural Gas ROMNEY: In the last four years, you cut permits and licenses on federal lands and federal waters in half. OBAMA: Not true Gov. Romney ABC's Jonathan Karl has the facts: Romney is right that oil and natural gases drilling permits and licenses (leases) are down, but they are not down as much as Romney says. Here are the actual numbers, Bureau of Land Management: Permits in the FY2009-2011 dropped by 37 percent compared to FY2006-2008 Leases in FY2009-2011 dropped by 42 percent compared to FY2006-2008 Romney is basing his claim on the total number of acres leased - and there are 56 percent fewer acres leased RULING: Not Quite Factual ----- ROMNEY: And production on government land is down by 14 percent and production on gas is down 9 percent. Oil production on public lands did drop by 14 percent in 2011 and natural gas production did drop by 9 percent (according to the US Energy Information Agency). BUT - overall, oil production is actually up slightly from 2009 to 2011. RULING: Not Quite Factual ABC's Matt Larotonda and Zunaira Zaki have more: Here's the numbers, courtesy of the Department of Energy. In a nutshell: The trends are correct, but can Obama claim credit? OIL PRODUCTION HIGHEST IN 16 YEARS? Oil production is at its highest level in 16 years according to the Energy Information Administration. In 1996 the US produced 2.3 billion barrels of crude oil, a number that steadily decreased until reaching a bottom in 2008 at 1.8 billion barrels. Production has been steadily increasing year over year since 2009 and at current trends will eclipse 1996 by year's end. NATURAL GAS PRODUCTION HIGHEST IN DECADES? There is no wiggle room here. The sheer volume of natural gas produced in the US is actually the highest it's ever been. The last downward trend from the industry occurred between 2001 and 2006, when volume decreased from 24.5 million cubic feet to 23.5 million. In 2011 the country produced 28.5 million cubic feet. COAL PRODUCTION HIGHEST IN DECADES? Numbers have been on a steady increase, yes. In 2011, the U.S. produced 1.09 billion tons, compared to 1.07 billion 3.6 in 2000 and 1.02 billion 1990 and 800 million in 1980. But, coal production in the U.S. took a dive between 2008 and 2009, when it fell from 1.17 billion short tons to 1.07 billion and 2011 hadn't reached those 2008 levels. WHAT ABOUT THOSE INCREASES IN COAL EMPLOYMENT? A very small chunk of the population is employed by the coal industry, an average of 84,000 so far this year, down from 86,000 last year. President Obama is referring to last year's average, which was the highest yearly average since 1997, also according to BLS. However, Obama cannot take all the credit for the increase oil and natural gas production -- he did not invent fracking. Similarly he cannot be blamed for all the problems the coal industry is having. In addition to fracking's rise, natural gas is so cheap that it has become the energy source of choice rather than coal in many instances. Did Obama Double the Deficit? ROMNEY: We have his own record which is we have four consecutive years where he said he was running for office he would cut the deficit in half, instead he has doubled it. ABC's Sunlen Miller has the facts: The Romney claim that Obama has "doubled the deficit" has been deemed false by numerous fact checking outlet including factcheck.org and PolitiFact. PoitiFact points out the only way to get to doubling is to use a different starting point, which is what the Romney campaign does. His campaign compares the current deficit to the final fiscal 2008 deficit of $458.6 billion. But that does not include the Wall Street bailout, first enacted under President Bush, which added more than $700 billion. One part though that the Romney claim is true. President Obama has not kept his promise to cut the deficit in half. PolitiFact argues that President Obama has actually cut the deficit by about 8 percent since he made the pledge in February of 2009. Did Obama Follow Romney's Advice and 'Take Detroit Bankrupt'? ROMNEY: I know he keeps saying, you want to x. Well, the president took Detroit bankrupt. You took General Motors bankrupt. You took Chrysler bankrupt. So when you say that I wanted to take the auto industry bankrupt, you actually did. And I think it's important to know that that was a process that was necessary to get those companies back on their feet, so they could start hiring more people. That was precisely what I recommended and ultimately what happened. See the video here. ABC's Jon Karl has the facts: There are two assertions here: 1) That President Obama "took Detroit bankrupt;" and, 2) That the president did "precisely what I recommended." On the first, Romney is right. Chrysler and General Motors did go through a pre-packaged Chapter 11 bankruptcy reorganization. On the second, he is wrong. The president's bailout included some $80 billion in public financing (the bailout in "auto bailout") to help Chrysler and GM to get through bankruptcy. Romney opposed direct public financing. This is a crucial distinction because most industry experts said there was no provide financing available. JON KARL'S RULING: Half True. ABC's Greg Krieg has more: Romney is technically correct; President Obama in March 2009 decided that the best way to revive the auto industry was for it to enter a brief bankruptcy. But it was not a bankruptcy like most other businesses will experience, as it lasted only one month and was backstopped by guarantees of billions of dollars from the federal government. Experts cite this as the significant difference between what President Obama did and what Romney proposed. Romney suggested that the automobile companies go through a standard bankruptcy, meaning they would have relied on private funds to bring them back to life. Obama, on the other hand, in a plan that began to take shape during the Bush administration - which kept the industry from afloat with more than $17 billion TARP funds diverted to Detroit -- ended up providing GM and Chrysler $80 billion in guaranteed taxpayer funds. In return, the government negotiated more favorable deals with the unions, who took wage hits and saw pension funds cut; creditors, who took a haircut on the money they were owed; and shareholders, who saw their stakes in the companies diminish in value. The concerned parties accepted these cutbacks as they were the preconditions for getting the government money - money that was not forthcoming from the private sector, as former auto czar Steve Rattner has said repeatedly, in the wake of the housing market and resulting banking industry collapses. The Real Unemployment Rate? Romney said the unemployment rate now is 7.8 percent and the rate when Obama took office was 7.8 percent, but he argued the true rate is much higher today. "If you calculate if people dropped out of the work force would be 10 percent." ABC's Zunaira Zaki has the facts: He is about half right. If the labor force participation rate was exactly what it was when Obama came into office the unemployment rate would be nearly 11 percent. But economists say that the labor force is shrinking not just because people are too discouraged to look for work, but also because there is a surge in baby boomers retiring and people are staying in school longer. Here are two examples of research on this: 1. According to research by Daniel Sullivan and his team at the Chicago Federal Reserve about half of the decline in the labor force since 2000 is because of an increase in the aging population. They that goes into this. 2. Mark Zandi of Moody's Analytics concurs. Through his research he has established that the labor force participation rate has fallen by approximately 2.5 percentage points since the Great Recession hit. Of this, 1.5 percentage points is due to demographics, including boomers who are retiring, and 1 percentage points is due to poor economy. ||||| Republican presidential candidate former Massachusetts Gov. Mitt Romney, left, listens as President Barack Obama answers a question from a member of the audience during the second presidential debate... (Associated Press) Mitt Romney wrongly claimed that it took 14 days for President Barack Obama to brand the assault on the U.S. Consulate in Libya a terrorist act. Obama yet again claimed that ending the Afghanistan and Iraq wars makes money available to "rebuild America," even though it doesn't. A look at some of their claims: OBAMA: The day after last month's attack on the U.S. Consulate in Benghazi, Libya, "I stood in the Rose Garden and I told the American people and the world that we are going to find out exactly what happened. That this was an act of terror and I also said that we're going to hunt down those who committed this crime." ROMNEY: "I want to make sure we get that for the record, because it took the president 14 days before he called the attack in Benghazi an act of terror." OBAMA: "Get the transcript." THE FACTS: Obama is correct in saying that he referred to Benghazi as an act of terrorism on Sept. 12, the day after the attack. From the Rose Garden, he said: "No acts of terror will ever shake the resolve of this great nation, alter that character, or eclipse the light of the values that we stand for. ... We will not waver in our commitment to see that justice is done for this terrible act." But others in his administration repeated for several days its belief that the violence stemmed from protests over an American-made video ridiculing Islam. It took almost a month before officials acknowledged that those protests never occurred. And Romney is right in arguing that the administration has yet to explain why it took so long for that correction to be made or how it came to believe that the attack evolved from an angry demonstration. ___ OBAMA: "Let's take the money that we've been spending on war over the last decade to rebuild America, roads, bridges, schools. We do those things, not only is your future going to be bright, but America's future is going to be bright as well." THE FACTS: What Obama didn't mention is that much of the money that has been paying for the wars in Iraq and Afghanistan was borrowed. In fact, the government borrows nearly 40 cents for every dollar it spends. Thus, using money that had been earmarked for wars to build schools and infrastructure would involve even more borrowing, adding to the federal deficit. ___ ROMNEY: "As a matter of fact, oil production is down 14 percent this year on federal land, and gas production was down 9 percent. Why? Because the president cut in half the number of licenses and permits for drilling on federal lands and in federal waters." OBAMA: "Very little of what Governor Romney just said is true. We've opened up public lands. We're actually drilling more on public lands than in the previous administration and my _ the previous president was an oilman." THE FACTS: Both statements ring true, as far as they go. Obama more correctly describes the bigger picture. According to an Energy Department study published in the spring, sales of oil from federal areas fell 14 percent between 2010 and 2011 and sales of natural gas production fell 9 percent, supporting Romney's point. The lower oil production was a result mainly of a moratorium on offshore drilling imposed by the Obama administration after the April 2010 BP oil spill in the Gulf of Mexico, the worst offshore oil spill in U.S. history. According to the same report, though, oil production from federal areas is up 13 percent since Obama took office despite last year's dip, and analysts say Gulf oil production is expected to soon exceed its pre-spill levels. Natural gas production from federal areas has been declining for years because drillers have found vast reserves of natural gas in formations under several states that are cheaper to access than most federally controlled areas. ___ OBAMA: "For young people who've come here, brought here oftentimes by their parents, have gone to school here, pledged allegiance to the flag, think of this as their country and understand themselves as Americans in every way except having papers, we should make sure we give them a pathway to citizenship. And that's what I've done administratively." THE FACTS: His administrative actions do not provide a pathway to citizenship. The administration is allowing as many as 1.7 million young illegal immigrants to apply to avoid deportation for up to two years and get a work permit. And the government has begun a policy of prosecutorial discretion under which illegal immigrants with longstanding ties to the U.S. and no criminal history are generally not arrested and deported by immigration authorities. But these steps do not extend legal status or a process resulting in citizenship. ___ ROMNEY: "I know he keeps saying, `You want to take Detroit bankrupt.' Well, the president took Detroit bankrupt. You took General Motors bankrupt. You took Chrysler bankrupt. So when you say that I wanted to take the auto industry bankrupt, you actually did. And I think it's important to know that that was a process that was necessary to get those companies back on their feet, so they could start hiring more people. That was precisely what I recommended and ultimately what happened." THE FACTS: What Romney recommended did not happen, and his proposed path probably would have forced General Motors and Chrysler out of business. He opposed using government money to bail out the automakers, instead favoring privately financed bankruptcy restructuring. But the automakers were bleeding cash and were poor credit risks. The banking system was in crisis. So private loans weren't available. Without government aid, both companies probably would have gone under and their assets would have been sold in pieces. ___ OBAMA: "And what I want to do is build on the 5 million jobs that we've created over the last 30 months in the private sector alone." THE FACTS: As he has done before, Obama is cherry-picking his numbers to make them sound better than they really are. He ignores the fact that public-sector job losses have dragged down overall job creation. Also, he chooses just to mention the past 30 months. That ignores job losses during his presidency up until that point. According to the Labor Department, about 4.5 million total jobs have been created over the past 30 months. But some 4.3 million jobs were lost during the earlier months of his administration. At this point, Obama is a net job creator, but only marginally. ___ ROMNEY: "The proof of whether a strategy is working or not is what the price is that you're paying at the pump. If you're paying less than you paid a year or two ago, why, then, the strategy is working. But you're paying more. When the president took office, the price of gasoline here in Nassau County was about $1.86 a gallon. Now, it's $4 a gallon. The price of electricity is up. If the president's energy policies are working, you're going to see the cost of energy come down." THE FACTS: Presidents have almost no effect on energy prices; most are set on financial exchanges around the world. When Obama took office, the world was in the grip of a financial crisis and crude prices _ and gasoline prices along with them _ had plummeted because world demand had collapsed. Crude oil prices have since risen even as U.S. oil production has soared in recent years because global demand is reaching new heights as the developing economies of Asia use more oil. Other energy prices have fallen during Obama's term. Electricity prices, when adjusted for inflation, are down, and homeowners are finding it much cheaper to heat their homes with natural gas. That's because natural gas production has surged, reducing prices both for homeowners and for utilities that burn gas to generate electricity. ___ OBAMA: "What I've also said is, for (those earning) above $250,000, we can go back to the tax rates we had when Bill Clinton was president." THE FACTS: Not exactly. The Bush tax cuts set the top income rate at 35 percent. Under Obama's proposal to raise taxes on households earning more than $250,000, the president would return the top rate to the 39.6 percent set during the Clinton administration. But he neglected to mention that his health care law includes a new 0.9 percent Medicare surcharge on households earning over that amount _ and that tax would be retained. The health care law also imposes a 3.8 percent tax on investment income for high earners. So tax rates would be higher for the wealthiest Americans than they were under Clinton. ___ ROMNEY: "I'm going to bring rates down across the board for everybody, but I'm going to limit deductions and exemptions and credits, particularly for people at the high end, because I am not going to have people at the high end pay less than they're paying now." THE FACTS: Romney is proposing to cut all income tax rates by 20 percent, eliminate the estate tax and the alternative minimum tax, maintain and expand tax breaks for investment income, and do it all without adding to the deficit or shifting the tax burden from the wealthy to the middle class. He says he would pay for the tax cuts by reducing or eliminating tax deductions, exemptions and credits, but he can't achieve all of his goals under the budget rules presidents must follow. The Tax Policy Center, a Washington research group, says in a study that the tax cuts proposed by Romney would reduce federal tax revenues by about $5 trillion over 10 years. The study concludes that there aren't enough tax breaks for the wealthy to make up the lost revenue, so the proposal would either add to the deficit or shift more of the tax burden onto the middle class. Romney's campaign cites studies by conservative academics and think tanks that say Romney's plan will spur economic growth, generating enough additional money to pay for the tax cuts without adding to the deficit or shifting the tax burden to the middle class. But Congress doesn't recognize those kinds of economic projections when it estimates the budget impact of tax proposals. ___ ROMNEY: "A recent study has shown that people in the middle class will see $4,000 a year in higher taxes as a result of the spending and borrowing of this administration." THE FACTS: Romney's claim is based on an analysis by the conservative American Enterprise Institute that examines the amount of debt that has accumulated on Obama's watch and in a potential second term and computes how much it would cost to finance that debt through tax increases. Annual deficits under Obama have exceeded $1 trillion for each year of his term. However, Obama is not responsible for all of the deficits that have occurred on his watch. Most of the federal budget _ like Medicare, food stamps, Medicaid and Social Security _ runs on autopilot, and no one in a leadership position in Washington has proposed deep cuts in those programs. And politicians in both parties voted two years ago to renew Bush-era tax cuts that have contributed to the deficit. Even under the strict spending cuts proposed by Romney, the debt would continue to rise, just not as quickly. ___ Associated Press writers Jonathan Fahey, Tom Krisher, Stephen Ohlemacher, Andrew Taylor, Bradley Klapper, Matthew Daly, Matthew Lee and Alicia A. Caldwell contributed to this report.

– As usual, the truth took a bit of a beating in last night's presidential debate. At least one fact was checked during the debate—Obama's assertion that he did, indeed, use the term "act of terror" to describe the attack on the US consulate in Libya the day after it occurred. A look at the post-debate fact-checking by the AP, ABC, the Washington Post, and Politico: Obama: "Let's take the money that we've been spending on war over the last decade to rebuild America, roads, bridges, schools." Actually, most of the money spent on the Iraq and Afghanistan wars is borrowed. And if we used that money for schools, it would mean yet more borrowing. Romney: "When the president took office, the price of gasoline here in Nassau County was about $1.86 a gallon. Now, it's $4 a gallon. The price of electricity is up. If the president's energy policies are working, you're going to see the cost of energy come down." Not necessarily, because in truth presidents have nearly zero effect on energy prices, since global financial exchanges set most of them. Additionally, other energy costs, like the price of natural gas, have fallen since Obama took office. Obama: "He called the Arizona law a model for the nation." No, what Romney was referring to was a federal electronic system used to verify the immigration status of new employees—not, as Obama said, the controversial Arizona immigration law. Romney: "He said … he would cut the deficit in half; instead he has doubled it." False, say numerous fact-checking outlets. But, while Obama has not doubled the deficit, neither has he cut it in half—more like 8%. Obama: "What I've also said is, for [those earning] above $250,000, we can go back to the tax rates we had when Bill Clinton was president." Yes, Obama would put the top rate back at 39.6%, as it was during Clinton's presidency. But since ObamaCare includes a new 0.9% Medicare surcharge and a 3.8% tax on investment income for those same households, tax rates would actually be higher for them than they were during the Clinton era.

A Chicago flight attendant for Spirit Airlines is in trouble for some photos taken on the tarmac at O'Hare Airport.Some passengers who had just boarded a Spirit Airline plane at O'Hare looked out the window and saw a flight attendant posing inside the jet engine well. One of the passengers contacted the I-Team in disbelief, asking if it was part of a new pre-flight checklist. When this flight attendant ended up working their flight, they took down her name and later found she had posted the pictures on her Facebook page.Some passengers witnessed the flight attendant standing on the tarmac in front of one of the plane's jet engines and then scrunched in front of the turbine blades.One person who contacted the I-Team said they couldn't believe what they were seeing and questioned whether it was proper and legal.They wrote down the name of the Spirit flight attendant, Ericka Paige Diehl, and looked her up on Facebook, where the tarmac photos were posted. One of them was being used as her profile picture.When we contacted her Tuesday, the 41-year-old Gurnee resident said at first that she didn't know anything about the photos on her Facebook page, and then said she wasn't "at liberty to discuss them."A few minutes later, however, the pictures vanished from Facebook and are now replaced by an inspirational message that says, "Your wings already exist, all you have to do is fly." Tonight her Facebook page has been taken down altogether.This afternoon a Spirit Airlines executive did discuss the photos with the I-Team, stating that "the activity portrayed in the photo absolutely goes against Spirit policy."Spirit spokesman Paul Berry said the airline will be investigating further and take appropriate action.After the flight took off from O'Hare, the concerned passenger asked that flight attendant what she was doing around the engines and her reply was "taking a picture." It may end up a picture to remember.A spokesperson for the Chicago Department of Aviation says, "in order to access the tarmac, an individual must be properly badged and/or under escort." It isn't clear whether Diehl or those taking the picture were authorized to be there and she hung up on the I-Team before that could be clarified. Prior to the photos disappearing from her Facebook page, however, in an exchange with friends Diehl did comment that the pictures could probably get her fired. ||||| A Spirit Airlines flight attendant found herself in the middle of a controversy after passengers spotted her posing for photos inside a jet engine. A passenger saw stewardess Ericka Paige Diehl posing for the photos while passengers boarded a Spirit Airlines flight at Chicago’s O’Hare International Airport. The passenger took down the flight attendant’s name and contacted ABC station WLS, asking if the photo was part of a new pre-flight checklist. The passenger then found out that Diehl posted the photos to her Facebook page, WLS reported. Spirit Airlines said in a statement about the photos, “The activity portrayed in the photo absolutely goes against Spirit policy.” But for many in the flying community, the outrage over Diehl’s photo shoot is unmerited. Sylvester Pittman, an aviation consultant with Airline Guys and a former flight attendant, said such photos are popular for flight crews. "I have a picture in a jet engine, and pretty much everybody that I know that has been a flight attendant ... it’s just one of those things that we like to do," Pittman said. Heather Poole, a flight attendant and author of the New York Times bestseller “Cruising Attitude,” also addressed the issue, writing on Twitter, “The photo of the flight attendant in the engine isn’t a problem. We all take them. The time that she decided to take it could be an issue.” Diehl did not respond to a request for comment, but told WLS she wasn’t at liberty to discuss the photos. The photos were removed from her Facebook page and replaced with the quote, “Your wings already exist, all you have to do is fly.”

– Passengers on a recent Spirit Airlines flight out of Chicago who were disturbed by an incident on the tarmac may not want to check out the #stewsforericka hashtag on Twitter. That's because there are loads of photos of flight attendants posing for snapshots in jet engine wells—a show of solidarity for attendant Ericka Paige Diehl, who's in hot water for taking such a photo at O'Hare airport, reports WLS. A passenger who saw her do it before the flight contacted WLS to ask if it was legal. When Diehl came aboard, someone got her name, looked her up online, and saw she had posted those tarmac pictures to her Facebook page. The photos, as well as her entire Facebook page, have since been scrubbed, the station notes. A Chicago Department of Aviation rep tells WLS that anyone on the tarmac has to be "properly badged and/or under escort." And, per ABC News, when Spirit Airlines got wind of the situation, it issued a statement that said, "The activity portrayed in the photo absolutely goes against Spirit policy." A spokesman says an investigation is underway. But fellow professional fliers are supporting Diehl, saying such photos are a time-honored tradition. "I have a picture in a jet engine, and pretty much everybody that I know that has been a flight attendant … it's just one of those things that we like to do," an ex-flight attendant tells ABC. Another tweets: "The photo of the flight attendant in the engine isn't a problem. We all take them. The time that she decided to take it could be an issue."

SECTION 1. SHORT TITLE. This Act may be cited as the ``Interstate Slamming Prevention Act of 1997''. SEC. 2. ENHANCEMENT OF PROTECTIONS. (a) Liability for Additional Charges.--Subsection (b) of section 258 of the Communications Act of 1934 (47 U.S.C. 258) is amended-- (1) by striking ``(b) Liability for Charges.--Any telecommunications carrier'' in the first sentence and inserting the following: ``(b) Liability for Charges.-- ``(1) Charges collected after violation.--Any telecommunications carrier''; and (2) by striking the second sentence and inserting the following: ``(2) Fees for changing back.--Any telecommunications carrier described in paragraph (1) shall also be liable to the carrier previously selected by the subscriber concerned for any fees associated with changing the subscriber back to the carrier previously selected, in accordance with such procedures as the Commission may prescribe. ``(3) Relation to other authority.--The remedies provided by this subsection are in addition to any other remedies available by law.''. (b) Additional Penalties.--Such section 258 is further amended by adding at the end the following: ``(c) Additional Penalties.--Any telecommunications carrier that violates the verification procedures described in subsection (a) shall be subject to such additional fines and penalties, including a forfeiture penalty under section 503(b)(1)(B) of this Act, as the Commission shall prescribe.''. (c) Additional Protections.--Such section 258 is further amended by adding at the end the following: ``(d) Additional Protections.--In order to provide subscribers with additional protections against changes in providers of telephone exchange service or telephone toll service in violation of the verification procedures described in subsection (a), the Commission may prescribe the following: ``(1) A requirement that telecommunications carriers establish toll-free telephone numbers in order to permit subscribers to register complaints regarding the execution of such changes in service, including the requirement that calls to such numbers be answered in not more than two minutes. ``(2) A requirement that telecommunications carriers provide the Commission such information relating to the complaints made to such carriers regarding such changes in service as the Commission considers appropriate.''. (d) Deadline for Rulemaking.--The Federal Communications Commission shall prescribe the regulations required by section 258 of the Communications Act of 1934, as amended by this section, not later than April 30, 1998. (e) Reports to Congress.-- (1) Initial report.--Not later than October 31, 1998, the Commission shall submit to Congress a report on unauthorized changes of subscribers' selections of providers of telephone exchange service or telephone toll service. The report shall include the following: (A) A list of the ten telecommunications carriers that, during the one-year period ending on the date of the report, were subject to the highest number of complaints of having executed unauthorized changes of subscribers from their selected providers of telephone exchange service or telephone toll service when compared with the total number of subscribers served by such carriers. (B) The telecommunications carriers, if any, assessed fines or penalties under section 258(c) of the Communications Act of 1934, as added by subsection (c) of this section, during that period, including the amount of each fine or penalty, and whether the fine or penalty was assessed as a result of a court judgment or an order of the Commission or was secured pursuant to a consent decree. (C) Whether or not subscribers should be authorized to bring a private cause of action against telecommunications carriers that change subscriber selections of providers of telephone exchange service or telephone toll service in violation of the procedures prescribed under section 258(a) of the Communications Act of 1934 and, if so, the advisability of establishing minimum statutory penalties for violations addressed by such causes of action. (D) Whether or not the fines and penalties imposed by the Commission under section 258(c) of the Communications Act of 1934, as so added, are sufficient to deter telecommunications carriers from changing subscriber selections of providers of telephone exchange service or telephone toll service in violation of such procedures. (2) Update.--Not later than one year after the date on which the Commission submits the report required by paragraph (1), and each year thereafter, the Commission shall submit to Congress an update of the previous report under this subsection which sets forth the information specified in subparagraphs (A) and (B) of that paragraph for one-year period preceding the date of the report concerned.

Interstate Slamming Prevention Act of 1997 - Amends the Communications Act of 1934 to make telecommunications carriers that execute illegal changes in a subscriber's selection of telephone exchange or toll service liable for any fees associated with changing the subscriber back to the carrier previously selected. Subjects carriers that violate verification procedures with respect to such changes to additional fines and penalties, including a forfeiture penalty. Authorizes the Federal Communications Commission (FCC), in order to provide subscribers with additional protections against such illegal changes, to require carriers to: (1) establish toll-free telephone numbers to register complaints regarding service changes; and (2) provide the FCC with information relating to such complaints. Directs the FCC to report annually to the Congress on unauthorized changes of subscribers' selections of telephone exchange or toll service.

SECTION 1. SHORT TITLE. This Act may be cited as the ``TARP Repayment and Termination Act of 2009''. SEC. 2. ADDITIONAL REPAYMENT PROCEDURES. (a) In General.--Title I of the Emergency Economic Stabilization Act of 2008 (12 U.S.C. 5201 et seq.) is amended by adding at the end the following new section: ``SEC. 137. ADDITIONAL REPAYMENT PROCEDURES. ``(a) Right of Repayment for Well Capitalized Institutions.--Any financial institution that has received or receives assistance under this title shall have the right to immediately repay all of such assistance, and the Secretary shall unconditionally accept such a payment, if-- ``(1) with respect to an insured depository institution, the appropriate Federal banking agency determines that such financial institution will be well capitalized after the repayment of all of such assistance; and ``(2) such financial institution has paid any dividend, interest, or other payment due to the Secretary by reason of the financial institution receiving assistance under this title. ``(b) Right of Repayment for Certain Bank Holding Companies.-- Notwithstanding subsection (a), a bank holding company assessed under SCAP shall have the right to immediately repay all assistance such company received under this title, and the Secretary shall unconditionally accept such a payment, if the Secretary, in consultation with the appropriate Federal banking agency, where applicable, determines that, upon the repayment of all of such assistance, such company-- ``(1) will remain in a position to continue to fulfill its role as an intermediary that facilitates lending to creditworthy households and businesses; ``(2) will be able to maintain capital levels that are consistent with supervisory expectations; ``(3) will be able to continue to serve as a source of financial and managerial strength and support to any subsidiary bank of such company; and ``(4) along with any subsidiary bank of such company, will be able to meet all ongoing funding requirements and obligations to counterparties while reducing reliance on Government capital and the TLGP. ``(c) Preferred Share Repurchase Levels.--With respect to preferred shares held by the Secretary, in making a full repayment of all assistance received by a financial institution under this title on or before September 30, 2009, such institution shall have the right to repurchase such preferred shares at-- ``(1) in the case of a preferred share purchased by the Secretary under this title, the same price the Secretary purchased such share for from the financial institution; and ``(2) in the case of a preferred share held by the Secretary as a result of the Secretary's exercise of a warrant received by the Secretary pursuant to section 113(d)(1)(B), the same price the Secretary purchased such warrant for from the financial institution. ``(d) Reduction in Authorization To Purchase in Corresponding Amount to Any Repayment.--Each time a financial institution makes a repayment of assistance provided under this title, the authorization to purchase authority under section 115 shall be reduced by a corresponding dollar amount. ``(e) Provision of Repayment Information.--Not later than 15 days after the Secretary is notified by a financial institution that such financial institution wants to immediately repay all assistance received by such institution under this title, the Secretary, in consultation with the appropriate Federal banking agency, if any, shall either-- ``(1) accept such repayment; or ``(2) notify such institution, in writing, that the individual financial position of such institution does not currently permit the repayment of such assistance, and include in such notice information detailing steps the institution can take to satisfy the Secretary and the appropriate Federal banking agency, if any, that the institution is in a position to repay such assistance. ``(f) Definitions.--For purposes of this section: ``(1) Appropriate federal banking agency.--The term `appropriate Federal banking agency' has the meaning given to such term in section 3(q) of the Federal Deposit Insurance Act (12 U.S.C. 1813(q)). ``(2) Bank holding company.--The term `bank holding company' has the meaning given to such term in section 2 of the Bank Holding Company Act of 1956 (12 U.S.C. 1841). ``(3) Insured depository institution.--The term `insured depository institution' has the meaning given to such term in section 3(c) of the Federal Deposit Insurance Act (12 U.S.C. 1813(c)). ``(4) SCAP.--The term `SCAP' means the Supervisory Capital Assessment Program conducted by the Board of Governors of the Federal Reserve System and other Federal regulators, the results of which were made public on May 7, 2009. ``(5) TLGP.--The term `TLGP' means the Temporary Liquidity Guarantee Program, implemented by the Federal Deposit Insurance Corporation by final rule on November 21, 2008. ``(6) Well capitalized.--With respect to an insured depository institution, the term `well capitalized' has the meaning given to such term in section 38(b)(1)(A) of the Federal Deposit Insurance Act (12 U.S.C. 1831o(b)(1)(A)).''. (b) Warrant Liquidation Requirement.--Section 111(g) of the Emergency Economic Stabilization Act of 2008 (12 U.S.C. 5221(g)) is amended by striking ``, at the market price, may liquidate warrants associated with such assistance'' and inserting ``shall liquidate warrants associated with such assistance at the current market price, except as otherwise provided in section 137(c)(2)''. (c) Repeal of Extension Authority.--Section 120 of the Emergency Economic Stabilization Act of 2008 (12 U.S.C. 5230) is amended-- (1) in subsection (a), by striking ``(a) Termination.-- The'' and inserting ``The''; and (2) by striking subsection (b). (d) Conforming Amendment.--The table of contents for the Emergency Economic Stabilization Act of 2008 is amended by inserting after the item relating to section 136 the following new item: ``137. Additional repayment procedures.''.

TARP Repayment and Termination Act of 2009 - Amends the Emergency Economic Stabilization Act of 2008 (EESA) to grant any financial institution that received or receives assistance under the Troubled Asset Relief Program (TARP) the right to repay all of it immediately if the institution will be well capitalized after such repayment and has made any payment due to the Secretary of the Treasury by reason of receiving such assistance. Allows bank holding companies assessed under the Supervisory Capital Assessment Program (SCAP) to repay all of their TARP assistance immediately if the Secretary determines that they meet specified criteria, including the ability, along with their subsidiary banks, to meet all ongoing funding requirements and obligations to counterparties while reducing reliance on government capital and the Temporary Liquidity Guarantee Program (TLGP). Directs the Secretary to notify financial institutions unable to repay their TARP assistance of detailed steps to take to put themselves in a position to make such repayment. Gives financial institutions making a full repayment of TARP assistance the right to repurchase preferred shares purchased or held by the Secretary as a result of the Secretary's exercise of warrants at the same price paid by the Secretary for such shares or warrants. Requires the Secretary to liquidate at the market price warrants associated with repaid TARP assistance. Eliminates the Secretary's authority to extend TARP beyond its termination date.

SECTION 1. SHORT TITLE. This Act may be cited as the ``Supplemental Social Security Income Flexibility Act of 1995''. SEC. 2. BLOCK GRANTS TO THE STATES FOR SUPPLEMENTAL SECURITY INCOME FOR THE DISABLED AND BLIND. (a) In General.--Title XVI of the Social Security Act (42 U.S.C. 1381-1383d) is amended by adding at the end the following new part: ``Part C--Block Grants to States for Supplemental Security Income for the Disabled and Blind ``purpose; implementation ``Sec. 1651. (a) Purpose.--The purpose of this part is to consolidate Federal assistance to the States for supplemental income for individuals who are disabled or blind (other than individuals who have attained age 65) into a single grant for such purpose, thereby giving States maximum flexibility to-- ``(1) require beneficiaries who are parents to ensure that their school-age children attend school; ``(2) require minors who are beneficiaries to attend school; ``(3) require parent beneficiaries to ensure that their children receive the full complement of childhood immunizations; ``(4) require beneficiaries not to use illegal drugs or abuse other drugs; ``(5) deny assistance to children solely on the basis that a child is unable to perform age-appropriate activities; ``(6) deny assistance to individiuals whose disabilities are primarily the result of their abuse of illegal or legal drugs, or alcohol; ``(7) deny assistance to illegal aliens; ``(8) require individuals who sponsor the residency of legal aliens to support those they sponsor; ``(9) involve religious and charitable organizations, voluntary associations, civic groups, community organizations, nonprofit entities, benevolent and fraternal orders, philanthropic entities, and other groups in the private sector, as appropriate, in the provision of assistance to needy disabled and blind individuals which the funding States receive under this part. ``(b) Implementation.--This purpose shall be implemented in accordance with conditions in each State and as determined by State law. ``payments to states ``Sec. 1652. (a) Amount.-- ``(1) In general.--Each State shall, subject to the requirements of this part, be entitled to receive quarterly payments for fiscal years 1997, 1998, 1999, and 2000 in an amount equal to 25 percent of the annual amount determined under paragraph (2) for such fiscal year for carrying out the purpose described in section 1651. ``(2) Annual amount.--The annual amount determined under this paragraph is equal to-- ``(A) in fiscal year 1997, 100 percent of the amounts received by the State in fiscal year 1994, or 100 percent of the average of amounts received by the State in fiscal years 1992, 1993, and 1994, whichever is greater, under part A of this title with respect to persons who are disabled or blind indivudals, other than individuals who have attained age 65 (as in effect in fiscal year 1994, or if applicable, in fiscal years 1992, 1993, 1994), and ``(B) in each fiscal year thereafter, 100 percent of the amount received by the State in the preceding fiscal year under this part (as in effect in such preceding fiscal year). ``(b) Funding Requirements.--The Secretary of the Treasury shall make quarterly payments described in subsection (a)(1) directly to each State in accordance with section 6503 of title 31, United States Code. ``(c) Expenditure of Funds; Rainy Day Fund.--Amounts received by a State under this part for any fiscal year shall be expended by the State in such fiscal year or in the succeeding fiscal year; except for such amounts as the State deems necessary to set aside in a separate account to provide, without fiscal limitation, for unexpected levels of assistance as a result of events which cause an unexpected increase in the need for providing supplemental income for individuals who are disabled or blind (other than individuals who have attained the age 65). Any amounts remaining in such segregated account after fiscal year 2000 shall be expended by a State for the purpose described in section 1651 of this part as in effect in fiscal year 2000. ``(d) Prohibition on Use of Funds.--Except as provided in subsection (e), a State to which a payment is made under this part may not use any part of such payment to provide medical services. ``(e) Authority To Use Portion of Grant for Other Purposes.-- ``(1) In general.--A State may use not more than 30 percent of the annual amount paid to the State under this part for a fiscal year to carry out a State program pursuant to any or all of the following provisions of law: ``(A) Part A of title IV of this Act. ``(B) Title XIX of this Act. ``(C) The Food Stamp Act. ``(2) Applicable rules.--Any amount paid to the State under this part that is used to carry out a State program pursuant to a provision of law specified in paragraph (1) shall not be subject to the requirements of this part, but shall be subject to the requirements that apply to Federal funds provided directly under the provision of law to carry out the program. ``administrative and fiscal accountability ``Sec. 1653. (a) Audits; Reimbursements.-- ``(1) Audits.-- ``(A) In general.--A State shall, not less than annually, audit the State expenditures from amounts received under this part. Such audit shall-- ``(i) determine the extent to which such expenditures were or were not expended in accordance with this part; and ``(ii) be conducted by an approved entity (as defined in subparagraph (B)) in accordance with generally accepted auditing principles. ``(B) Approved entity.--For purposes of subparagraph (A), the term `approved entity' means an entity that is-- ``(i) approved by the Secretary of the Treasury; ``(ii) approved by the chief executive officer of the State; and ``(iii) independent of any agency administering activities funded under this part. ``(2) Reimbursement.-- ``(A) In general.--Not later than 30 days following the completion of an audit under this subsection, a State shall submit a copy of the audit to the State legislature and to the Secretary of the Treasury. ``(B) Repayment.--Each State shall pay to the United States amounts ultimately found by the approved entity under paragraph (1)(A) not to have been expended in accordance with this part plus 10 percent of such amount as a penalty, or the Secretary of the Treasury may offset such amounts plus the 10 percent penalty against any other amount in any other year that the State may be entitled to receive under this part. ``(b) Additional Accounting Requirements.--The provisions of chapter 75 of title 31, United States Code, shall apply to the audit requirements of this section. ``(c) Reporting Requirements; Form, Contents.-- ``(1) Annual reports.--A State shall prepare comprehensive annual reports on the activities carried out with amounts received by a State under this part. ``(2) Content.--Reports prepared under this section-- ``(A) shall be for the most recently completed fiscal year; ``(B) shall be in accordance with generally accepted accounting principles, including the provisions of chapter 75 of title 31, United States Code; ``(C) shall include the results of the most recent audit conducted in accordance with the requirements of subsection (a) of this section; and ``(D) shall be in such form and contain such other information as the State deems necessary-- ``(i) to provide an accurate description of such activities; and ``(ii) to secure a complete record of the purposes for which amounts were expended in accordance with this part. ``(3) Copies.--A State shall make copies of the reports required under this section available for public inspection within the State. Copies also shall be provided upon request to any interested public agency, and each such agency may provide its views on such reports to the Congress. ``(d) Administrative Supervision-- ``(1) Role of the secretary of the treasury.-- ``(A) In general.--The Secretary of the Treasury shall supervise the amounts received under this part in accordance with subparagraph (B). ``(B) Limited supervision--The supervision by the Secretary of the Treasury shall be limited to-- ``(i) making quarterly payments to the States in accordance with section 1652(b); ``(ii) approving the entities referred to in subsection (a)(1)(B); and ``(iii) withholding payment to a State based on the findings of such an entity in accordance with subsection (a)(2)(B). ``(2) Other federal supervision.--No administrative officer or agency of the United States, other than the Secretary of the Treasury and, as provided for in section 1654, the Attorney General, shall supervise the amounts received by the States under this part or the use of such amounts by the States. ``(e) Limited Federal Oversight.--With the exception of the Department of the Treasury as provided for in this section and section 1654 of this part, no Federal department or agency may promulgate regulations or issue rules regarding the purpose of this part. ``nondiscrimination provisions ``Sec. 1654. (a) No Discrimination Against Individuals.--No individual shall be excluded from participation in, denied the benefits of, or subjected to discrimination under any program or activity funded in whole or in part with amounts received under this part on the basis of such individual's-- ``(1) disability under section 504 of the Rehabilitation Act of 1973 (29 U.S.C. 794); ``(2) sex under title IX of the Education Amendments of 1972 (20 U.S.C. 1681 et seq.); or ``(3) race, color, or national origin under title VI of the Civil Rights Act of 1964 (42 U.S.C. 2000d et seq.). ``(b) Compliance.--If the Secretary of the Treasury determines that a State, or an entity that has received funds from amounts received by the State under this part, has failed to comply with a provision of law referred to in subsection (a), except as provided for in section 1655 of this part, the Secretary of the Treasury shall notify the chief executive officer of the State and shall request the officer to secure compliance with such provision of law. If, not later than 60 days after receiving such notification, the chief executive officer fails or refuses to secure compliance, the Secretary of the Treasury may-- ``(1) refer the matter to the Attorney General with a recommendation that an appropriate civil action be instituted; ``(2) exercise the powers and functions provided under title VI of the Civil Rights Act of 1964 (42 U.S.C. 2000d et seq.), title IX of the Education Amendments of 1972 (20 U.S.C. 1681 et seq.); or section 505 of the Rehabilitation Act of 1973 (29 U.S.C. 794a), (as applicable); or ``(3) take such other action as may be provided by law. ``(c) Authority of Attorney General; Civil Actions.--When a matter is referred to the Attorney General pursuant to subsection (b)(1), or if the Attorney General has reason to believe that an entity is engaged in a pattern or practice in violation of a provision of law referred to in subsection (a), the Attorney General may bring a civil action in an appropriate district court of the United States for such relief as may be appropriate, including injunctive relief. ``nondiscrimination and institutional protections for religious providers ``Sec. 1655. (a) Purpose.--The purpose of this section is to allow the participation of religious organizations as providers of assistance to disabled or blind individuals funded under this part without impairing or diminishing the religious character or freedom of such organizations. ``(d) Nondiscrimination.--Religious organizations shall be eligible as providers of assistance to disabled or blind individuals as provided for under this part. Neither the Federal Government nor a State receiving funds under this part shall discriminate against an organization which is or applies to be a provider of assistance on the basis that the organization has a religious mission or purpose. ``(c) Religious Character and Freedom.-- ``(1) In general.--Notwithstanding any other provision of law, any religious organization participating as a provider of assistance funded under this part shall retain its independence from Federal, State, and local governments, including such organization's control over the definition, development, practice, and expression of its religious beliefs. Such an organization may select, employ, promote, discipline, and dismiss its clerics and other ecclesiastics, directors, officers, employees, and volunteers on the basis of religion, a religious belief, or a religious practice. However, a religious organization shall not deny disabled or blind individuals the benefits of any assistance funded under this part on the basis of religion, a religious belief, or refusal to participate in a religious practice. ``(2) Additional safeguards.--Neither the Federal Government nor a State shall require a religious provider of assistance to-- ``(A) alter its form of internal governance, or form a separate, nonprofit corporation to receive and administer assistance funded under this part; or ``(B) alter real estate or facilities used to provide such assistance, including but not limited to the removal of religious art, icons, scripture, or other symbols; in order to be eligible to be a provider of assistance under this part. ``(3) Fiscal accountability.-- ``(A) In general.--Except as provided in subparagraph (B), any religious organization providing assistance funded under this part shall be subject to the same regulations as other providers to account in accord with generally accepted auditing principles for the use of such funds provided under this part. ``(B) Limited audit.--Religious organizations may segregate Federal funds provided under this part into separate accounts, and then only the financial assistance provided with those funds shall be subject to audit. ``(d) Compliance.--A religious organization which has its rights under this section violated may enforce its claim by asserting a civil action for such relief as may be appropriate, including injunctive relief or damages, in an appropriate district court of the United States against the entity or agency that commits such violation. ``(e) Rights of Beneficiaries of Assistance.-- ``(1) In general.--If a beneficiary has a bona fide objection to the religious character of the organization or institution from which the beneficiary is receiving assistance funded under this part, each State shall provide such beneficiary a certificate, redeemable with any other provider of assistance funded under this part, for services the value of which is no less than the value of the funding received by the religious provider from a State to provide assistance funded under this part for such individual. ``(2) Prohibition on providing cash in exchange for certificates.--No provider of assistance funded under this part shall provide a beneficiary a cash amount in exchange for a certificate provided for under paragraph (1).''. (b) Conforming Amendment.--Section 1602 of the Social Security Act (42 U.S.C. 1381a) is amended by striking ``Every'' and inserting ``(a) Every'' and by adding at the end the following new subsection: ``(b) No person who is a disabled or blind individual (other than a person who has attained age 65) shall be an eligible individual or eligible spouse for purposes of this part with respect to any month beginning after September 30, 1996, but shall be eligible for services to the disabled or blind funded under part C of this title.''. SEC. 3. CONFORMING AMENDMENTS TO THE BUDGET ACT. The Balanced Budget and Emergency Deficit Control Act of 1985 (2 U.S.C. 900 et seq.) is amended in section 255(h) (2 U.S.C. 905(h), by striking ``Supplemental Security Income Program (75-0406-0-1-609); and'' and inserting ``Supplemental Security Income Program and block grants to States for supplemental security income for disabled individuals; and''. SEC. 4. EFFECTIVE DATE. The amendments and repeals made by this Act shall take effect on October 1, 1996.

Supplemental Social Security Income Flexibility Act of 1995 - Amends title XVI (Supplemental Security Income) (SSI) of the Social Security Act to add a new part, Part C: Block Grants to States for Supplemental Security Income for the Disabled and Blind. States that the purpose of this part is to consolidate Federal SSI assistance to the States into a single grant, thereby giving States maximum flexibility to make State-specific requirements for individuals receiving benefits. Identifies certain requirements, including those relating to school attendance, immunizations, drug abuse, illegal aliens, and charitable, religious, and nonprofit organizations. Caps SSI spending levels. Directs the Secretary of the Treasury to supervise the amounts received under Part C.

It's probably impossible to count the times someone has written that video games are a business as big as or bigger than Hollywood. But long before the Halos and the Sims and the Call of Dutys and the Maddens began bringing in billions of dollars, the world was dominated by a simple yellow character munching his way through a maze of dots, trying to avoid getting eaten by ghosts. On May 22, 1980, a Japanese company called Namco Bandai released a game in Japan called Puck-Man. The title was rejected in the United States because some worried that the "P" would chip off the cabinet and look like an "F." Regardless, a global phenomenon was born that day. And on Saturday, Pac-Man celebrates its 30th anniversary. And unlike so many of the hit games that have come and gone since then, the little yellow disc with the missing pie-slice for a mouth has become a legend in the video games industry, as well as an inspiration for many of the best-known designers in the field. "I think there's no question that Pac-Man was sort of a watershed event in the popularity and possibilities of video games," said Richard Garriott, a veteran designer known for his pioneering work on Ultima and Ultima Online, as well as his leading roles on Lineage, City of Heroes, and Tabula Rasa. "It was by no means the first [hit game], but earlier offerings [like Asteroids and Pong], no matter how compelling [they were] to nerds like me...Pac-Man was really the first [that reached] what I would call the broad cross-section of society, men and women. It was really the first time, where people looked at video games not merely as this odd thing that teenage boys would [pump] their quarters into, but which had much broader social significance." That may seem like a bold statement, but there is evidence to back the idea that Pac-Man may be the most influential video game of all time. For instance, the Guinness Book of World Records named Pac-Man as the best-known video game character on Earth, beating out stalwarts like the Mario Brothers and Sonic the Hedgehog. Guinness also lists Pac-Man as the most successful coin-operated game ever. And while it may not have the attention of the typical male teen gamer, Pac-Man certainly still has a place in society today. There are popular iPhone and iPad versions of the game, many bars still feature the arcade machines. And on Friday, Google is breaking new ground by unveiling its first-ever interactive and playable home page logo, a full-featured, 255-level version of Pac-Man (see video below), built from the ground up but maintaining an almost perfect look and feel of the original. "We are very excited about the Google [logo] project," Namco CEO Kenji Hisatsune told CNET by e-mail. "This being the first time Google has ever included sound or made a [logo] playable demonstrates just how big of an impact Pac-Man has made." Now playing: Watch this: Google's Pac-Man doodle Marcin Wichary, the Google senior user-experience designer who led the Pac-Man logo project, agreed that the game has made a huge difference in many people's lives, including his. Pac-Man was released when "there were a lot of space shooters," said Wichary. "It was the first game that tried to approach it a little bit differently. It tries to tell a story and it's not a violent game. It's very friendly, with colorful characters and music. I think that was important...It's just so amazing that Pac-Man's so timeless. Even 30 years later, it's actually [still] such a blast to play it." One of the biggest reasons that Pac-Man, and its many sequels, especially 1981's Ms. Pac-Man, were hits, is because they were very simple. Pick up one of today's more complicated $60 Xbox 360 titles and if you're not a hard-core gamer, you can easily get so confused and intimidated that you quickly give up. But Pac-Man wasn't like that. "Pretty much anyone could watch someone playing it for 10 seconds and understand everything about it," said Steve Meretzky, a veteran game designer who created famous Infocom titles like Leather Goddesses of Phobos and the game version of Hitchhiker's Guide to the Galaxy. "It was a game everyone felt comfortable playing, even in the setting of an arcade, and that's why it became so universally popular." In addition, Meretzky said, Pac-Man had something for everyone, be it a first-timer or someone who had spent countless dollars in quarters on it. "It's just incredibly well-crafted," he said. "It balances pretty well. Even if you are a super expert and you're playing it for the zillionth time, level one isn't boring. It still feels fun to play. And vice-versa. Even if you're a rank newbie, level one doesn't feel like a horrible crushing experience. It's still fun to play." Simple rules Anyone who has played Pac-Man can probably sum up the rules in a few seconds, as Meretzky suggested. But it's interesting to look on Namco's official Pac-Man site and look at a description of the rules and the game play: The player controls Pac-Man while attempting to eat all the dots in the maze and avoid getting caught by the ghosts through an extremely simple user interface consisting only of a single joystick. There are four ghosts who chase Pac-Man, each with different names and personalities, such as the chaser and the ambusher. The ghosts work together to try to corner and catch Pac-Man. As for Pac-Man, he can power up by eating one of four blinking power pellets located in the corners of the maze. The power pellet will provide Pac-Man with the ability to eat ghosts for a limited amount of time. When a ghost is eaten, its eyes will return to the ghost home in the center of the maze, where it regenerates after a certain amount of time. Moreover, there are two warp tunnels on either side of the maze, which will slow down the ghosts while Pac-Man escapes to the other side of the screen. In each level, bonus items appear after a certain number of dots are eaten. There are a variety of bonus items, including fruits like cherries and strawberries, the "Galaxian" boss flagship, and a key. In order to get a really high score, these items should not be missed. Pac-Man starts the game with three lives, and loses a life each time a ghost touches Pac-Man. Obtaining more than 5,000 points earns the player an extra life. Ultimately, it is Pac-Man's simplicity that brought it such a huge audience. Yet to designers like Meretzky, trying to replicate that was no easy task. Meretzky recalled designing a title called Hodj 'n Podj, which featured several reworked classic games, including a remake of Pac-Man. "It made me much more appreciative of the game," he said. "It was really, really hard to get the game balance right, and get the [artificial intelligence] of the ghosts right. You look at Pac-Man and you think it's such a simple game and an easy game to clone. But it's hard to get the balance right." To Garriott, who in addition to being a famous game designer is also known for his recent trip to the International Space Station, one main reason that Pac-Man has held up so well over time is that the game's designer, Toru Iwatani, nailed what Garriott calls the "fundamentals of game play." He said that classic games like chess, checkers, and Go are all conceptually easy to understand, but take a lifetime to master. "I think Pac-Man does very well on that metric," Garriott said. "It's easy to understand and sit down and try to play. But then [you see its] wide variety of foundational strategies that unfold only after you have played many, many times." Partially-eaten pizza According to Namco's Hisatsune, Pac-Man--or, more properly, Puck-Man--was inspired by a partially eaten pizza of Iwatani's. It's hard to say exactly how the designer made the connection between the unfinished pie and the hit game, but Hisatsune, Iwatani presciently saw something that would inspire a gaming empire. "During the early stages of the arcade industry," Hisatsune said, "most games were skewed toward a male audience. Iwatani-san knew there would be no future in arcade games unless the games being produced were also tailored to women and couples. This is when Pac-Man was born." Now, on the eve of the game's 30th anniversary, Namco is far from letting go of its gold mine. It is still working on new versions, new characters, and new platforms. "We would like to keep planning how Pac-Man will evolve and what he will be like when he reaches his 50th anniversary," Hisatsune said. "The fact that Pac-Man is as popular now as he was 30 years ago makes me believe that [the game] will be relevant in the future." Of course, there are those who find it hard to imagine that so many years have gone by since that auspicious day, May 22, 1980. "It can't really be 30 years," Meretzky said. "It has to be 10. Right?" ||||| About this capture Hey—we've moved. Visit The Keyword for all the latest news and stories from Google

– Today's teenage gamers probably aren't big on Pac-Man, but they might want to give thanks tomorrow as the arcade icon turns 30, writes Daniel Terdiman for CNET. It just may be the most influential video game of all time. Yeah, titles like Pong came first, but Pac-Man, with its deceptive simplicity, was the first to cross over beyond the world of nerdy teens into mainstream popularity. "Unlike so many of the hit games that have come and gone since then, the little yellow disc with the missing pie-slice for a mouth has become a legend in the video games industry, as well as an inspiration for many of the best-known designers in the field," writes Terdiman. Google's tribute to the over-the-hill icon went live this morning, the company blog notes; click here to check it out.

Israel's newly retired spy chief thinks Iran will not be able to build a nuclear bomb before 2015, Israeli media reported Friday _ further pushing back Israeli intelligence estimates of when Tehran might become a nuclear power. Meir Dagan, who left his post as head of the Mossad intelligence service this week, said Thursday that Iran's nuclear program had been delayed by unspecified "measures" employed against it, according to the Israeli daily Yediot Ahronot. Other Israeli media reported Dagan's prediction, citing "closed conversations" he held Thursday before leaving his post as head of Israel's covert intelligence arm. An Israeli government spokesman would not comment Friday. As recently as 2009, Israeli Defense Minister Ehud Barak said Iran would be able to build a nuclear bomb by 2011. But since then the projected deadline has been extended. The Israeli Cabinet minister in charge of strategic affairs, Moshe Yaalon, said last week it would take the Iranians at least three years to develop a nuclear weapon. The assessment by Dagan adds another year to that estimate. Dagan also said Israel "should not hurry to attack" Iran, according to the Yediot Ahronot report. Israel officially supports the diplomatic efforts in place to curb Iran's nuclear ambitions, but has not ruled out the possibility of a military strike. Iran claims its nuclear program is aimed at producing electricity, but Israel, many of Iran's Arab neighbors, the U.S. and other Western countries are convinced the Iranian program is aimed at producing weapons. Iran has blamed Israel for disruptions in its nuclear program. In November, assailants on motorcycles attached magnetized bombs to the cars of two Iranian nuclear scientists as they drove to work in Tehran, killing one and wounding another. At least two other Iranian nuclear scientists have been killed in recent years. In addition, a computer worm known as Stuxnet is thought to have caused the Iranians serious technical problems in the centrifuges used for uranium enrichment _ a process that can be used both to produce reactor fuel and material for nuclear warheads. Tehran's nuclear program is of particular concern to Israel, which sees a nuclear weapon in Iranian hands as an existential threat. Iran funds Islamic militant groups on Israel's borders, such as the Palestinian Hamas and the Lebanese Hezbollah, and Iran's president, Mahmoud Ahmadinejad, has said Israel should be "wiped off the map." The U.N. Security Council imposed four rounds of sanctions on Iran after Tehran refused to halt its program. The council's five permanent members, along with Germany, are set to hold a new round of talks with Iran in late January. Iran recently invited Hungary, which currently holds the rotating European Union presidency, Russia, China and other countries to tour its nuclear sites before those talks. It pointedly did not invite the U.S. or other Western powers on the Security Council. ||||| BERLIN—International talks with Iran over its nuclear program are set to resume in Istanbul on January 20, a spokeswoman for the European Commission said. The participants—Russia, China, the U.S., U.K., France, Germany and Iran—are still working on an agenda for the discussions, which are scheduled to begin the evening of Jan. 20 and last at least through Jan. 21, the spokeswoman said. The goal of the international powers going into the talks is to convince Iran to take steps toward abandoning its nuclear ambitions. The U.S. and its allies believe Iran is using what it claims is a civilian nuclear ...

– Israel shouldn't rush to attack Iran because Mahmoud Ahmadinejad is still four years away from developing a nuclear weapon, says the newly retired spy chief of Mossad. He claims that certain "measures" have pushed back Tehran's timetable a few years, reports AP. He didn't say what those measures were exactly, but Iran is pretty sure Israel is behind the Stuxnet worm and an attack on two of its scientists. On another front, international talks with Iran about its nuclear ambitions resume Jan. 20, notes the Wall Street Journal.

a supernova ( sn ) event in our own galaxy will lead to a large flux of neutrinos arriving at the earth within the space of a few seconds . the only such event detected so far has been supernova 1987a @xcite , at a time when neutrino detectors were considerably smaller and less advanced than they are today . hence the detection of another such event , which should occur within the near future , will result in a great deal of new information regarding both supernovae and neutrinos @xcite . the majority of these neutrinos are produced thermally during the supernova event , where temperatures can reach around 10 mev @xcite , and carry away most of the released energy . they are emitted with a distribution with is approximately of the fermi - dirac form , with a temperature which differs for the neutrino flavours . broadly the electron neutrinos should have the lowest temperature as they scatter the most in the star and so decouple at the largest radius . by contrast electron anti - neutrinos scatter less with the stellar matter and so are emitted at a higher temperature , and the remaining heavy flavours have a higher temperature still . various authors have demonstrated that , in addition to neutrinos , other more exotic particles could be produced thermally during the supernova event @xcite . these particles @xmath0 are ` dark ' in the sense that they interact only weakly with visible matter and so are difficult to detect , except perhaps in extreme environments such as a hot post - supernova star . indeed if such particles interact with neutrinos through scattering or annihilation they will alter the various temperatures of the neutrino spectrum @xcite , which could result in observable effects on earth . however the exact temperatures are not well known and depend upon assumptions related to the structure of the star during thermal production , specifically the dependence of density and temperature with radius @xcite . in this work we seek to understand how the scattering with neutrinos of additional thermally - produced mev - mass particles will alter the neutrino temperatures , given the potentially large uncertainties in the modelling of the star during the supernova event . using this information we quantify to what extent current and future experiments can exploit measurements of the neutrino temperatures to constrain the existence of such particles . we focus specifically on the difference between the temperatures of the neutrino flavours , since dark sector scattering with neutrinos drives the temperatures of the different flavours towards a single value . this is important since , as shown in figure [ fig : spectra ] , a spectrum which is the sum of two ( or more ) different temperatures is clearly distinct from one which is made up of only one temperature . from a supernova , whose spectrum is a combination of fermi - dirac distributions with two temperatures at 5 mev and 8 mev . we compare this with spectra with only a single temperature of either 5 mev and 8 mev and the combined spectrum.,scaledwidth=49.0% ] in section [ sec : production ] we outline how the temperatures of the neutrino species are calculated and in section [ sec : chi ] we describe how these are modified in the presence of new states @xmath0 . in section [ sec : detection ] we give the formulae for the neutrino flux spectrum at earth from a galactic supernova and how this is converted to the spectrum in a detector . we use these formulae in section [ sec : cons ] to set projected upper limits on the scattering between @xmath0 and neutrinos using a bayesian analysis and compare these to other constraints in section [ sec : comparison ] . we conclude in section [ sec : conc ] . in this section we outline how the different neutrino temperatures @xmath4 and number densities @xmath5 are calculated using the diffusion equation , followed in section [ sec : chi ] where we describe how these are affected by scattering with a new ` dark ' particle @xmath0 . our approach is approximate , and we do not claim accuracy on par with numerical simulations of the supernova event @xcite , however it is sufficient for our purpose of understanding how sensitive the different neutrino temperatures are to modelling uncertainties in the star during thermal production . the diffusion equation takes the form @xcite , @xmath6 where @xmath7 is the radial distance from the centre of the star , a prime denotes an @xmath7-derivative , @xmath8 is the diffusion coefficient , @xmath9 is the self - annihilation cross section for the particle , @xmath10 is the number density of the particle when it is in thermal equilibrium with the stellar matter , @xmath11 is the lorentz factor and @xmath12 is the lifetime of the particle . the value of @xmath7 where @xmath5 departs from its equilibrium value i.e. where @xmath13 is called the neutrinosphere radius ( in the case of neutrinos at least ) . this is effectively the radius where the neutrinos can be said to have decoupled from the stellar matter . likewise the corresponding temperature @xmath4 of the star at this radius is the neutrinosphere temperature . the neutrinosphere temperature determines the observed neutrino temperature on earth from the supernova . this can be approximated by reducing equation to the following expression @xcite , @xmath14 and solving for @xmath4 , where we assume that @xmath10 is , @xmath15 \mathrm{exp } \left(\frac{- m}{t(r ) } \right ) , \label{eqn : equib}\ ] ] where @xmath16 is the mass of the particle ( e.g. a neutrino or dark particle @xmath0 ) . we approximate the radial dependence of the baryon density and temperature of the star after the supernova event using a simple empirical model , whose parameters we can vary easily to understand the effect of their uncertainty on the different neutrino flavour temperatures . as such we assume the following power - law forms for the baryon density @xmath17 and the baryon temperature @xmath4 , @xmath18 where @xmath19 , @xmath20 , @xmath21 , @xmath22 and @xmath23 are in principle all free parameters . some particular models take for example : @xmath24 , @xmath25 , @xmath26 mev , @xmath27 km and @xmath28 @xmath29 @xcite ( model a ) or @xmath30 , @xmath31 , @xmath32 mev , @xmath33 km and @xmath34 @xmath29 @xcite ( model b ) . for our projected limits we will treat these variables as nuisance parameters , since the exact form of the profile is not known and can vary significantly . the value of the neutrinosphere temperature is fixed by the scattering cross section between neutrinos and the other particles of the star , particularly baryons , and the self - annihilation cross section of the neutrinos . the former effect arises through the diffusion coefficient , which if we assume dominant scattering from baryons equals @xmath35 @xcite , where @xmath36 is the velocity of the neutrinos , @xmath37 is the scattering cross section with baryons through the channel labelled by @xmath38 ( e.g. neutral - current ) and @xmath39 is a factor relating to the relative abundance of neutrons and protons . electron neutrinos scatter the most frequently and so have the smallest value of @xmath8 due to their interaction with neutrons via the charged current interaction as well as the sub - dominant neutral current channel . electron anti - neutrinos by contrast scatter with protons via charged current interactions instead , whose density is several orders of magnitude smaller than neutrons in the star , resulting in a larger value of @xmath8 . the remaining ` heavy ' flavours have the largest @xmath8 and so the largest neutrinosphere temperature as they dominantly scatter with neutrons and protons via neutral current interactions , whose cross section is smaller than that for charged - current scattering . this all holds to first order , however effects from more detailed modelling of the supernova can alter this simple picture @xcite . we now consider the possibility that an additional species of particle @xmath0 , which interacts only weakly with the visible sector , is produced thermally in the supernova and scatters with neutrinos , thereby contributing to the diffusion coefficient @xmath8 . under the assumption that such new interactions are flavour - blind the diffusion coefficient becomes , @xmath40^{-1 } , \label{eqn : diff_chi}\ ] ] where @xmath41 is the number density of the new species @xmath0 and @xmath42 is its scattering cross section with neutrinos . importantly if @xmath43 then the value of @xmath8 will be dominated by the flavour - blind scattering with the dark sector @xmath0 , and so we might expect the neutrino temperatures to approach a single value regardless of flavour . the exact temperature dependence of @xmath42 depends on how the @xmath0 particles interact with neutrinos . for example following refs . @xcite if one assumes either scalar @xmath0 interacting with neutrinos via the exchange of a new fermion , or fermionic @xmath0 interacting with neutrinos via a new gauge boson , then @xmath44 is a reasonable assumption provided that the masses of @xmath0 and the exchange particle are not degenerate . for the former case of scalar @xmath0 we envisage a term in the lagrangian of form @xmath45 where @xmath46 is a heavy right - handed fermion which mediates the interaction between @xmath0 and neutrinos . this then leads to a thermally averaged scattering cross section of form @xmath47 . such an interaction term could also result in the generation of a mass term for the neutrinos in analogue to the see - saw mechanism ( see e.g. ref . hence our projected constraints are partly motivated as a method of constraining these neutrino mass models , however they can be interpreted in the context of other models and we have checked our results in the case of alternative assumptions , such as @xmath48 , and find no significant deviation from the conclusions presented here . furthermore the form of @xmath41 depends on the interactions of the @xmath0 particle with nucleons and electrons as well as neutrinos . in this work we assume that the @xmath0 are in thermal equilibrium up to a radius larger than the neutrinosphere for all flavours . this means that @xmath0 has either a large annihilation cross section or decay rate and/or interactions with baryons in order to keep the @xmath0 coupled to the hot stellar matter . we return to this assumption in section [ sec : comparison ] . we restrict our analysis to particles with mass @xmath49 mev to avoid constraints from nucleosynthesis on thermally produced light particles @xcite . this also means that the density of @xmath0 will be boltzmann suppressed compared to that for neutrinos , meaning that the latter still dominate the energy transport from the supernova ( see section [ sec : comparison ] for further discussion ) . ( of form @xmath50 ) with a mass of 10 mev . the dotted line represents @xmath51 , the dashed represents @xmath52 and the solid line is for the remaining heavy flavours . we show such dependence for two different assumptions on the profile of the matter in the star during the supernova event , labelled as model a and model b.,scaledwidth=49.0% ] we show in figure [ fig : temps_plot ] the values of the three different neutrino temperatures as a function of @xmath42 for the two different example empirical models of the star introduced earlier as model a and model b. these have been calculated using equation ( [ eqn : thermal_decoupling ] ) with @xmath8 from equation ( [ eqn : diff_chi ] ) . there are two main points to note here : the first is that the values of the neutrino temperatures depend strongly on the choice of empirical model for the star during the supernova event . the second is that when @xmath42 is large enough the values of the temperatures for each flavour become equal , and that this value of @xmath42 is more robust to changes in the empirical model of @xmath53 and @xmath54 than the absolute temperatures themselves . therefore if we are to obtain anything useful from analysing the temperatures of neutrinos from a supernova it will likely come from comparing the relative temperatures between species , rather than their absolute values . _ hence although the values of the temperatures depend strongly on the model of the hot star for a given value of @xmath42 , the number of distinct temperatures which make up the total neutrino spectrum is much less sensitive . _ in section [ sec : cons ] we use this fact to understand what can be learned in future detectors by determining the number of different temperatures in the overall spectrum . in this section we outline how neutrinos from a supernova will be detected on earth using either inverse - beta decay capture of electron anti - neutrinos @xcite in experiments such as super - kamiokande @xcite or hyper - kamiokande @xcite or via coherent nuclear recoils in direct detection experiments @xcite . the former has the advantage of greater statistics , while the latter is insensitive to the mixing between neutrino flavours on their way to earth and allows for all three temperatures to in principle be measured . the expected spectrum of neutrinos @xmath55 from a supernova takes the form of a pinched fermi - dirac distribution @xcite ( neglecting features from mixing effects @xcite ) , @xmath56 where @xmath57 is the temperature of the particular neutrino species ( of which there are a number @xmath58 ) , @xmath59 is the relative luminosity of species @xmath38 compared to the total , @xmath60 is the pinching parameter , which we assume to be zero in this work for simplicity , and @xmath61 is a dirac integral , taking the form @xmath62 multiplying @xmath63 by the total flux from a galactic supernova @xmath64 gives the flux spectrum on earth . we estimate the total flux using the time - integrated supernova luminosity @xmath65 ergs @xcite , the average energy of each flavour @xmath66 and the distance to the supernova @xmath67 kpc ( i.e. close to the galactic centre ) . hence the total integrated flux spectrum of neutrinos from a galactic supernova takes the form , @xmath68 detectors such as super - kamiokande and hyper - kamiokande @xcite will detect supernova neutrinos primarily via inverse - beta decay ( i.e. @xmath69 ) due to the large cross section for this process @xcite . the events are identified by positrons whose energies @xmath70 are related simply to the neutrino energies @xmath71 as @xmath72 . the differential detection rate is then the product of @xmath73 with the cross section for inverse beta decay . however the calculation is complicated by the fact that we only detect @xmath52 which will be made up of neutrinos which were in various different flavours at the point of production . hence the spectrum of the @xmath52 at earth should be composed of two distinct temperatures provided that @xmath42 is negligible and that the different anti - flavours mix on their way to earth . this also means that the temperature of the @xmath51 flavour is not measurable with this detection method , and so there will only at most be two temperatures . hence when we determine projected limits on @xmath42 we need to take account of the potentially uncertain values of the relative luminosities @xmath59 for the two remaining temperatures . by contrast , the detection of neutral current scattering allows all of the neutrino temperatures to be detected regardless how how the neutrinos mix on their way to earth . direct detection experiments looking for dark matter could be sensitive to supernova neutrinos via this channel . in this case the neutrinos scatter coherently on nuclei with a differential cross section @xmath74 @xcite leading to a differential scattering rate of nuclear recoil events taking the form , @xmath75 where @xmath76 is the minimum neutrino energy able to induce a recoil of energy @xmath70 for a nucleus of mass @xmath77 . in this case since the detection method is via neutral - current scattering all three temperatures can be detected and the relative luminosities @xmath59 are set at the point of production ( ignoring possible new physics effects during transit ) . with dark sector particles @xmath0 in an experiment detecting neutrinos via inverse beta decay ( similar to super kamiokande @xcite ) or by nuclear scattering . the different spectra correspond to the neutrino flavour temperatures predicted assuming model a in figure [ fig : temps_plot].,title="fig:",scaledwidth=49.0% ] + with dark sector particles @xmath0 in an experiment detecting neutrinos via inverse beta decay ( similar to super kamiokande @xcite ) or by nuclear scattering . the different spectra correspond to the neutrino flavour temperatures predicted assuming model a in figure [ fig : temps_plot].,title="fig:",scaledwidth=49.0% ] shown in figure [ fig : spectra_sigmas ] are the expected spectra in both types of detector considered here , for different values of @xmath42 . as @xmath42 increases the spectra shift towards having a single temperature as opposed to being composed of multiple distinct temperatures . this is most obvious with knowledge of the whole spectrum , and so in order to discriminate between the different spectra we need to be able to observe both low and high energies events , and so a low threshold is crucial . we are now in a position to derive projected exclusion limits on the dark sector interaction cross section with neutrinos @xmath42 , using the spectra calculated in this section . how strong these limits can be will be determined by how effectively we can discriminate the different constituent temperatures in the spectrum from the supernova , and the systematic uncertainties from the modelling of the star during the supernova event . in this section we determine the projected sensitivity of future multi - tonne experiments to the scattering cross section between dark sector particles and neutrinos , produced thermally in a galactic supernova . such interactions will alter the temperatures of the different neutrino flavours ( see figure [ fig : temps_plot ] ) , however exactly how this happens depends crucially on how well we know the dependence of the baryon density and temperature of the star during the supernova event . hence our projections must incorporate this uncertainty in the choice of profile . to do this we perform a bayesian analysis , while parametrising the empirical model of the hot star with nuisance parameters , which we marginalise over . for such parameters we use @xmath23 , @xmath22 and @xmath21 from equations ( [ eqn : nbprof ] ) and ( [ eqn : tprof ] ) , which determine how steeply the temperature and baryon density fall off with radius . the posterior density , used to determine the exclusion sensitivity for a particular data - set @xmath78 , is @xmath79 where @xmath80 represents the likelihood function , which we assume to be of poisson form to compare the expected spectrum for a given stellar profile and value of @xmath42 ( e.g. figure [ fig : spectra_sigmas ] ) to simulated data . @xmath81 are the prior distributions for the three nuisance parameters and the signal parameter @xmath42 . we then set a projected limit by generating a number of simulated data - sets @xmath82 given a particular detector mass and use the posterior summed over these data - sets @xmath83 . we generate these data - sets by assuming a particular set of temperatures and relative luminosities for each flavour . integrating @xmath84 from @xmath85 up to @xmath3 of the total posterior probability then gives us our projected exclusion limits . the choice of priors for the nuisance parameters represents how well these quantities , and thus the profile of the baryonic matter during neutrino ( and @xmath0 ) thermal production , are known . since we are interested in understanding how well @xmath42 can be probed even if the stellar profile is poorly known we choose priors which cover a wide - range of @xmath22 , @xmath23 and @xmath21 . in principle however the profile uncertainty could be reduced using e.g. simulations of the supernova event @xcite . figure [ fig : lims ] shows projected limits for either detection via inverse - beta decay or coherent nuclear scattering ( other detection methods have also been proposed e.g. ref . @xcite ) assuming priors which equal a constant in the following ranges ( and zero otherwise ) , @xmath86 \\ \mathcal{p}(q ) & \in & [ 1,10 ] \\ \mathcal{p}(t_0 ) & \in & [ 2,20 ] \ , \mathrm{mev},\end{aligned}\ ] ] with @xmath20 and @xmath19 fixed at values of @xmath27 km and @xmath28 @xmath29 . the choice of these priors is arbitrary , and we have intentionally chosen them to represent a large degree of uncertainty by spanning a wide range of possible stellar profiles , including the values of @xmath23 , @xmath22 and @xmath21 from model a and model b introduced earlier . greater knowledge of the profile of the star during neutrino production would reduce the range of these priors and so would likely strengthen our projected limits . in order to determine these projected limits we have simulated datasets in detectors of various target masses . since we do not know _ a priori _ what spectra they will observe , depending on the physics during the supernova and the mixing of the neutrino flavours , we have set limits under two different assumptions . for example in the left panel of figure [ fig : lims ] we set limits under the assumption that the spectrum of @xmath52 from the supernova event is either made up of a single fermi - dirac spectrum of temperature 5 mev or of two spectra with temperatures of 5 mev and 8 mev . for the former case we do not know whether @xmath0-neutrino scattering has forced the temperatures of the different anti - neutrino flavours together , whether a different mechanism has brought the temperatures together , or whether the electron anti - neutrino flux is dominated by neutrinos which were produced in that same flavour at the supernova . hence conservatively all one can do is set an upper limit on @xmath42 at the level where it would drive the temperature of the neutrinos to be smaller than 5 mev , given uncertainties on the stellar profile . however by comparison the projected limit on @xmath42 will be much stronger if a spectrum with a combination of temperatures is observed ( see also figure [ fig : spectra ] ) , which is the more likely scenario if the neutrino flavours mix on their way to earth . in this case as can be seen from the left panel of figure [ fig : lims ] the exclusion limit will be at the level of @xmath1 @xmath2 for super kamiokande @xcite , assuming two temperatures at 5 mev and 8 mev with equal relative luminosities . this is partly due to it being easier to discriminate different spectra with information on multiple temperatures , given the large uncertainties in the profile of the baryons after the supernova event . essentially with enough statistics a spectrum with two temperatures can be easily distinguished from one with only one temperature , even if the uncertainties on the values of the temperatures themselves are significant . the limit which hyper kamiokande @xcite should be able to set should be at least an order of magnitude stronger due to the larger number of events it will be able to observe . we show in the right panel of figure [ fig : lims ] the projected limits for a xenon - based experiment which observes supernova neutrinos through coherent nuclear scattering with a combined spectrum of three temperatures at 8 mev , 5 mev and 3.5 mev , similar to the result for model a in figure [ fig : temps_plot ] . in this case there is no uncertainty from the mixing of the different neutrino flavours since the detection is via the neutral - current , however the smaller target masses of experiments which exploit this effect , mainly dark matter direct detection experiments , means that they are unlikely to build up enough statistics to compete with super or hyper kamiokande . nevertheless a xenon - based detector with a mass around 20 tonnes ( e.g. darwin @xcite ) should be able to set a limit on the dark sector scattering cross section with neutrinos provided the threshold for nuclear recoils can be lowered to around 0.1 kev . this may be possible if such detectors look only at ionisation signals , for which the threshold is generally lower , since discrimination between nuclear and electronic recoils will not be required for such a significant event burst . the key advantage of the direct detection experiments is their ability to measure all three potential temperatures , while relying on inverse beta decay capture of @xmath52 allows only the temperatures of the anti - flavours to be measured . this is important as any effect within the supernova which could drive the temperatures together without new physics , for example that of ref . @xcite , or an effect which suppresses the mixing of the neutrino flavours in transit to earth would weaken our limits , especially in the case of @xmath52 detection . hence it is possible that the limit from coherent nuclear scattering is more robust to such effects , beyond the simplistic model of the star during the supernova event which we have used here . indeed this motivates the construction of such detectors up to 100 tonnes or more in mass , as an effective way of detecting all flavours of supernova neutrinos with high precision . we now consider such @xmath0 particles within a wider context by comparing our projected limits with other constraints . these particles should be only weakly coupled at most to visible matter to avoid having been already detected , however even so there are other methods of probing their interactions . indeed the temperature of the neutrinos is not the only method of using a supernova to constrain new particles , which interact only weakly with visible matter . for example the @xmath0 particle needs to have a mean free path for scattering which is shorter than the size of the hot star during the supernova event , to avoid excessively rapid cooling @xcite i.e. a new particle produced thermally but which scatters less often with the stellar matter than neutrinos do could make the energy loss rate too rapid . hence the @xmath0 particle likely needs interactions in addition to those with neutrinos in order to evade this cooling bound , and so our assumption of thermal equilibrium for @xmath0 is reasonable . to study thermal equilibrium in more detail we follow a similar argument using equation ( [ eqn : diff ] ) . broadly speaking if @xmath8 is small then @xmath5 is close to @xmath10 and so the particles are in thermal equilibrium ( or close to it ) . in this case a small value of @xmath8 means that the @xmath0 particles scatter frequently with the stellar matter . indeed assuming that @xmath0 maintains its equilibrium through interactions with the baryonic matter of the star we can make use of the mean free path for scattering @xmath87 to estimate the required scattering cross section . we need that @xmath88 , where @xmath89 is the linear size of the hot star . assuming that @xmath90 , where @xmath91 is the scattering cross section between baryonic matter and @xmath0 we have that @xmath92 . the value of @xmath17 depends on the model for the hot star i.e. equations ( [ eqn : nbprof ] ) and ( [ eqn : tprof ] ) and the temperature . if we assume that we need the @xmath0 to be in thermal equilibrium at temperatures above 1 mev then using parameters from model a we have that @xmath93 @xmath29 . hence if @xmath94 km we have the approximate requirement that @xmath95 @xmath2 for thermal equilibrium of the @xmath0 particles down to temperatures of 1 mev however this bound could be several orders of magnitude higher for more extreme models of the hot star during neutrino thermal production . equation ( [ eqn : diff ] ) also tells us that the self - annihilation cross section of @xmath0 should be non - zero for thermal equilibrium to be established , though this depends partly on whether @xmath0 can decay . assuming that @xmath0 has a lifetime much longer than the time - period for thermal production then the larger the value of @xmath8 the larger the self - annihilation cross section @xmath9 needs to be for @xmath5 to be equal ( or close ) to @xmath10 . solving equation ( [ eqn : diff ] ) numerically for the number density @xmath5 of the @xmath0 particles with @xmath96 @xmath2 confirms that @xmath0 are in thermal equilibrium down to temperatures of around 1 mev for a self - annihilation cross section @xmath97 @xmath98s@xmath99 , which is the scale required for @xmath0 to be the dark matter of the universe . values of @xmath9 larger than this are also allowed for thermal equilibrium , however in this case the relic density of @xmath0 will be too small for it to be dark matter . bounds also exist on the temperature of @xmath100 and @xmath101 produced in supernovae from the abundances of light elements @xcite . this constraint is complimentary to the one studied in this work and could in principle be used to constrain @xmath42 . as mentioned previously thermally produced new states will disrupt nucleosynthesis unless their mass is above @xmath102 mev @xcite and there are bounds from the number of relativistic degrees of freedom in the early universe @xcite . there also exist constraints on the scattering of @xmath0 with neutrinos from the damping of structure in the universe @xcite , though this only applies if @xmath0 forms the dominant component of dark matter ( set by the size of @xmath9 ) . at @xmath3 confidence for a 100 kilo - tonne experiment looking for neutrinos through inverse beta decay ( ibd ) capture , with the upper limit from requiring that dark matter scattering with neutrinos does not destroy small - scale structure in the universe @xcite . the latter only applies if @xmath0 forms the dominant component of the dark matter.,scaledwidth=49.0% ] in figure [ fig : lims_mass ] we show our projected limit for an experiment with a mass of 100 kilo - tonnes detecting @xmath52 via inverse beta decay for a range of @xmath0 masses above the bound from nucleosynthesis @xcite . our projected limit is stronger than that from the damping of structure in the universe @xcite for masses up to around 100 mev , above which the density of @xmath0 in the hot star becomes too small due to boltzmann suppression to lead to any significant scattering with neutrinos , unless @xmath42 is very large . if a supernova event were to occur in our own galaxy then a large number of neutrino events should be detected on earth in the space of a few seconds . the majority of the neutrinos are produced thermally with a temperature depending on their flavour : electron neutrinos scatter the most with baryonic matter and so have the smallest temperature , while electron anti - neutrinos are slightly hotter and the other heavy flavours hotter still @xcite . in this work we have considered the prospect of additional mev - mass ` dark ' particles @xmath0 being produced thermally during the supernova , which scatter with neutrinos @xcite . we have focused on the effect these new states would have on the temperatures of the different neutrino flavours due to scattering , with cross section @xmath42 . this leads to an extra term in the diffusion coefficient @xmath8 i.e. equation ( [ eqn : diff_chi ] ) , which alters the hierarchy of the temperatures for each flavour , as shown in figure [ fig : temps_plot ] . however quantifying this effect is made difficult by the uncertainty in the modelling of the density and temperature of the star during thermal production . our main emphasis has been on predicting the ability of current and future experiments to be able to measure the neutrino spectrum with enough precision to place constraints on @xmath42 . we show some example spectra in figure [ fig : spectra_sigmas ] . since the temperatures of the different neutrino flavours depend sensitively on the model for the star during thermal production of neutrinos ( and potentially @xmath0 also ) , we have performed a bayesian analysis where we marginalise over the parameters of a simple analytic stellar model ( equations ( [ eqn : nbprof ] ) and ( [ eqn : tprof ] ) ) . we have considered experiments looking at coherent nuclear scattering , such as direct detection experiments , and those looking for @xmath52 via inverse beta decay capture , such as super and hyper kamiokande @xcite . as can be seen in figure [ fig : lims ] , we have found that super kamiokande could place an upper limit at the level of @xmath1 @xmath2 for 10 mev mass @xmath0 particles and hyper kamiokande could be able to set a limit an order of magnitude stronger still . furthermore as shown in figure [ fig : lims_mass ] our projected limits are potentially the strongest constraint on @xmath0 scattering with neutrinos up to a mass around 100 mev . however these projections are essentially the ` best case scenario ' in the sense that we assume there are no additional effects on top of our simplified model for the star during neutrino production which could bring the temperatures of @xmath52 and @xmath103 closer together @xcite . such effects could weaken these limits considerably . indeed our analysis was performed using a simple empirical parametrisation to model the star during neutrino production , in order to understand how the uncertainties in this model impact our ability to constrain @xmath42 . it is likely that there are further effects which will alter the expected temperatures of the neutrino species @xcite . however we expect that the value of @xmath42 where the temperatures of the different flavours become equal will remain fairly robust to additional modelling uncertainties . for detectors looking at coherent nuclear scattering the limits should in principle be more robust to such effects , since they will be able to measure all neutrino flavours through neutral - current scattering . however experiments which exploit this channel , for example dark matter direct detection experiments @xcite , are generally much less massive than super kamiokande and so can not exploit as many statistics to measure the neutrino spectrum . this motivates construction of an 100 tonne mass liquid - xenon experiment or similar as potentially the ultimate neutral - current supernova detector , with regards to effects from @xmath0-@xmath104 scattering . the author thanks john beacom and malcolm fairbairn for helpful comments and suggestions . the research leading to these results has received funding from the european research council through the project darkhorizons under the european union s horizon 2020 program ( erc grant agreement no.648680 ) . 30ifxundefined [ 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 link:\doibase 10.1103/physrevlett.58.1490 [ * * , ( ) ] link:\doibase 10.1103/physrevd.76.083007 [ * * , ( ) ] , link:\doibase 10.1103/physrevlett.68.3834 [ * * , ( ) ] @noop * * , ( ) link:\doibase 10.1103/physrevd.51.1499 [ * * , ( ) ] , link:\doibase 10.1086/375130 [ * * , ( ) ] , link:\doibase 10.1093/ptep / ptv079 [ * * , ( ) ] , link:\doibase 10.1103/physrevd.54.1194 [ * * , ( ) ] link:\doibase 10.1103/physrevd.83.113006 [ * * , ( ) ] , link:\doibase 10.1103/physrevlett.96.211302 [ * * , ( ) ] , @noop ( ) , link:\doibase 10.1086/323379 [ * * , ( ) ] , link:\doibase 10.1103/physrevlett.104.251101 [ * * , ( ) ] \doibase 10.1051/0004 - 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a supernova event in our own galaxy will result in a large number of neutrinos detected on earth within the time - frame of a few seconds . these neutrinos will have been produced thermally with , in principle , three distinct temperatures for the electron , anti - electron and remaining heavy flavours respectively . we revisit the possibility that new mev - mass particles @xmath0 are also produced thermally during the event , which scatter with the neutrinos and alter their temperatures . our main emphasis is on the detectability of this effect using the neutrino spectrum , given the large uncertainty on the temperature and density profiles of the stellar matter . by marginalising over the parameters of a simple analytic model for the stellar profile , we find that super kamiokande could place an upper limit on the scattering cross section at the level of @xmath1 @xmath2 for 10 mev mass @xmath0 particles at @xmath3 confidence . a direct - detection - like experiment would be less susceptible to systematic uncertainties in the neutrino production and mixing , but this would need a target mass around 100 tonnes in order to acquire enough statistics to compete with super kamiokande .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Medicare Home Health Telehealth Access Act of 2005''. SEC. 2. ACCESS TO TELEHEALTH SERVICES IN THE HOME. (a) In General.--Section 1895(e) of the Social Security Act (42 U.S.C. 1395fff(e)) is amended to read as follows: ``(e) Coverage of Telehealth Services.-- ``(1) In general.--The Secretary shall include telehealth services that are furnished via a telecommunication system by a home health agency to an individual receiving home health services under section 1814(a)(2)(C) or 1835(a)(2)(A) as a home health visit for purposes of eligibility and payment under this title if the telehealth services-- ``(A) are ordered as part of a plan of care certified by a physician pursuant to section 1814(a)(2)(C) or 1835(a)(2)(A); ``(B) do not substitute for in-person home health services ordered as part of a plan of care certified by a physician pursuant to such respective section; and ``(C) are considered the equivalent of a visit under criteria developed by the Secretary under paragraph (3). ``(2) Physician certification.--Nothing in this section shall be construed as waiving the requirement for a physician certification under section 1814(a)(2)(C) or 1835(a)(2)(A) for the payment for home health services, whether or not furnished via a telecommunication system. ``(3) Criteria for visit equivalency.-- ``(A) Standards.--The Secretary shall establish standards and qualifications for categorizing and coding under HCPCS codes telehealth services under this subsection as equivalent to an in-person visit for purposes of eligibility and payment for home health services under this title. In establishing the standards and qualifications, the Secretary may distinguish between varying modes and modalities of telehealth services and shall consider-- ``(i) the nature and amount of service time involved; and ``(ii) the functions of the telecommunications. ``(B) Limitation.--A telecommunication that consists solely of a telephone audio conversation, facsimile, electronic text mail, or consultation between two health care practitioners is not considered a visit under this subsection. ``(4) Telehealth service.-- ``(A) Definition.--For purposes of this section, the term `telehealth service' means technology-based professional consultations, patient monitoring, patient training services, clinical observation, assessment, or treatment, and any additional services that utilize technologies specified by the Secretary as HCPCS codes developed under paragraph (3). ``(B) Update of hcpcs codes.--The Secretary shall establish a process for the updating, not less frequently than annually, of HCPCS codes for telehealth services. ``(5) Conditions for payment and coverage.--Nothing in this subsection shall be construed as waiving any condition of payment under sections 1814(a)(2)(C) or 1835(a)(2)(A) or exclusion of coverage under section 1862(a)(1). ``(6) Cost reporting.--Notwithstanding any provision to the contrary, the Secretary shall provide that the costs of telehealth services under this subsection shall be reported as a reimbursable cost center on any cost report submitted by a home health agency to the Secretary.''. (b) Effective Date.-- (1) The amendment made by subsection (a) shall apply to telehealth services furnished on or after October 1, 2006. The Secretary of Health and Human Services shall develop and implement criteria and standards under section 1895(e)(3) of the Social Security Act, as amended by subsection (a), by no later than July 1, 2006. (2) In the event that the Secretary has not complied with these deadlines, beginning October 1, 2006, a home health visit for purpose of eligibility and payment under title XVIII of the Social Security Act shall include telehealth services under section 1895(e) of such Act with the aggregate of telecommunication encounters in a 24-hour period considered the equivalent of one in-person visit. SEC. 3. REMOTE MONITORING PILOT PROJECTS. (a) Pilot Program Authorized.--The Secretary of Health and Human Services (in this section referred to as the ``Secretary'') shall initiate and carry out pilot projects (each in this section referred to as a ``pilot project'') in a variety of geographic locations that provide incentives to home health agencies to utilize home monitoring and communications technologies that will-- (1) enhance health outcomes for individuals enrolled under parts A and B of title XVIII of the Social Security Act; and (2) reduce part A and B program expenditures for institutional and other providers, practitioners, and suppliers of health care items and services. (b) Individuals Within the Scope of Pilot.-- (1) In general.--The Secretary shall specify, in accordance with this subsection, the criteria for identifying those individuals who shall be considered within the scope of the pilot projects under this section for purposes of the incentive payments under subsection (c) and for assessment of the effectiveness of the home health agency in achieving the objectives of the section. (2) Participation of individuals not receiving home health services.--Participation in these pilot projects shall not be limited to individuals receiving home health services under part A or part B of title XVIII of the Social Security Act. (c) Incentive Payments.-- (1) In general.--Subject to paragraph (2), the Secretary shall pay to each home health agency participating in a pilot project an amount for each year under the pilot project equal to at least 50 percent of the reduction in expenditures under such parts realized for such year due to the agency's participation in the project. The computation of such reduction shall be based on the Secretary's estimate of the amount by which the amount of expenditures under such parts for the individuals under the pilot project is less than the amount that would have been expended under such parts for such individuals if the project were not implemented. In determining the estimate, the Secretary may use estimates for expenditures for individuals who are not participating in the project and who are comparable to individuals participating in the project. (2) Limitation on expenditures.--The Secretary shall limit incentive payments under this subsection as necessary to ensure that the aggregate expenditures under title XVIII of the Social Security Act (inclusive of such incentive payments) with respect to patients within the scope of the pilot projects do not exceed the amount that the Secretary estimates would be expended under such title if the pilot projects under this section were not implemented. (d) Construction.--Nothing in this section shall limit the amount of payment (other than under subsection (c)) a home health agency may receive for home health services provided to eligible individuals under part A or part B of title XVIII of the Social Security Act. (e) Implementation Date.--The Secretary shall implement the pilot projects authorized by this section no later than nine months after the date of the enactment of this Act. (f) Expansion of the Pilot Project.--If the Secretary determines that any of the pilot projects-- (1) result in a decrease in Federal expenditures under title XVIII of the Social Security Act; and (2) maintain or enhance health outcomes for the participating beneficiaries, the Secretary may initiate or extend comparable projects in additional areas.

Medicare Home Health Telehealth Access Act of 2005 - Amends title XVIII (Medicare) of the Social Security Act to revise the current requirements for Medicare coverage of telehealth services under the prospective payment system. Requires the Secretary of Health and Human Services to treat as a home health visit any telehealth services furnished by a home health agency via a telecommunication system to an individual receiving home health services, if the telehealth services: (1) are ordered as part of a plan of care certified by a physician; (2) (as under current law) do not substitute for in-person home health services ordered as part of a plan of care certified by a physician; and (3) are considered the equivalent of a visit under criteria developed by the Secretary. Directs the Secretary to initiate and carry out projects in a variety of geographic locations that provide incentives to home health agencies to utilize home monitoring and communications technologies that will: (1) enhance health outcomes for individuals enrolled under Medicare parts A and B; and (2) reduce part A and B program expenditures for institutional and other providers, practitioners, and suppliers of health care items and services. Authorizes the Secretary to pay incentive payments to each home health agency participating in a pilot project. Provides that, if the Secretary determines that any of the pilot projects results in decreased federal Medicare expenditures, and maintains or enhances health outcomes for the participating beneficiaries, the Secretary may initiate or extend comparable projects in additional areas.

the w and z bosons were first discovered at cern more than two decades ago @xcite . since then their properties have been extensively studied by different experiments to test the standard model ( sm ) predictions and to explore the physics beyond - the - sm . at the large hadron collider ( lhc ) @xcite , w and z bosons will be produced with large rates . a large set of w / z bosons will help us with detector commissioning initially and enable us to perform a large variety of w / z physics studies with early lhc data . the production mechanism of w / z bosons at the lhc is well known . higher order predictions of many w / z observables have been carried out . for example , a recent next - to - leading order calculation @xcite of total w and z cross sections predicted that the cross sections are tens to hundreds of nanobarns for z and w bosons , respectively . a calculation of differential cross section as a function of boson rapidity at next - to - next - leading order has also been carried out by c. anastasiou _ et al . _ @xcite . in these theoretical predictions , errors due to the parton distribution functions ( pdf ) dominated total theoretical errors . the pdf error could be partially canceled out if we study ratios of cross sections , such as the lepton charge asymmetry between @xmath0 and @xmath1 production , which is defined to be , @xmath2 this charge asymmetry probes the valence - sea quark ratio in protons . measurements of these observables at the lhc will enable us to test higher order calculations and provide new insights into proton structure . the compact muon solenoid ( cms ) experiment is a 4@xmath3 general - purpose hadron - collider detector , which is suitable for high-@xmath4 physics studies at the lhc . the central feature of the compact muon solenoid apparatus is a superconducting solenoid , of 6 m internal diameter , providing a field of 3.8 t. within the field volume are the silicon pixel and strip tracker , the crystal electromagnetic calorimeter ( ecal ) and the brass / scintillator hadronic calorimeter ( hcal ) . muons are measured in gaseous detectors embedded in the iron return yoke . besides the barrel and endcap detectors , cms has extensive forward calorimetry . the ecal has an energy resolution of better than 0.5% above 100 gev . the hcal , when combined with the ecal , measures jets with a resolution @xmath5 . the calorimeter cells are grouped in projective towers , of granularity @xmath6 at central rapidities and @xmath7 at forward rapidities . the muons are measured in the pseudorapidity window @xmath8 , with detection planes made of three technologies : drift tubes , cathode strip chambers , and resistive plate chambers . matching the muons to the tracks measured in the silicon tracker results in a transverse momentum resolution between 1 and 5% , for @xmath9 values up to 1 tev/@xmath10 . the first level of the cms trigger system , composed of custom hardware processors , uses information from the calorimeters and muon detectors to select ( in less than 1 @xmath11s ) the most interesting events ( only one bunch crossing in 1000 ) . the high level trigger processor farm further decreases the event rate from 100 khz to 100 hz , before data storage . a much more detailed description of cms can be found elsewhere @xcite . the monte carlo ( mc ) simulation used in the following studies was generated with the pythia @xcite event generator , where the cteq5l @xcite pdf model was used . the center - of - mass energy was assumed to be 10 tev . the generated events were then passed through the full cms detector simulation with geant4 @xcite . physics objects such as muons and electrons were reconstructed with standard cms offline reconstruction sequence . the missing transverse energy ( met ) was reconstructed using energy deposits in cms calorimeters . at the lhc , leptonic decays of w / z bosons were used to study the properties of w / z bosons . the experimental signature of a w boson is a high-@xmath4 lepton and large met due to presence of a neutrino in the final state . cms conducted analyses to measure the inclusive w boson cross section in both muon and electron decays @xcite . the trigger used in @xmath12 analysis is a single muon trigger with a minimum @xmath4 threshold of 15 gev . the efficiency is above 90% . the cms single muon trigger system has coverage up to a pseudorapidity of @xmath13 2.1 . the selection of @xmath12 candidates was done by first requiring an isolated muon with @xmath14 25 gev and muon pseudorapidity @xmath152.0 . here the isolation is the @xmath4 sum of all tracks in a cone of radius 0.3 around the muon direction , normalized to the muon @xmath4 . this normalized isolation is required to be less than 0.09 . the qcd dijet background was largely suppressed by the isolation requirement . other processes , such as drell - yan , @xmath16 , @xmath17 , could also fake a @xmath12 event . background events were further suppressed by requiring transverse mass , where @xmath18 is the angular difference between muon and missing transverse moment in the plane transverse to the beam direction . ] @xmath19 gev , as shown in fig . [ fig : wxsec ] , where the expected @xmath20 signal and background events for an integrated luminosity of 10 pb@xmath21 is shown . cms also studied the inclusive w boson cross section in electron decays . a single electron trigger was used , which has an efficiency of about 97% . an electron candidate was required to have transverse energy ( @xmath22 ) deposit in the cms ecal detector @xmath23 30 gev and @xmath132.5 . the shower shape of a electron candidate was also required to be consistent with an electromagnetic interaction . comparing to the muon channel analysis , in addition to background processes such as , qcd dijet production , drell - yan , @xmath16 , @xmath17 , photon plus jet production also contributes . the qcd dijet background was significantly reduced by an isolation requirement . here isolation was computed using transverse components of energy deposits in cms calorimeters and tracks in a cone of radius 0.4 around the electron direction . figure [ fig : wxsec ] shows the reconstructed met distribution for @xmath24 signal and background events after all event selections were applied . the @xmath25 cross section is related to the background subtracted number of signal events , @xmath26 , @xmath27 where @xmath28 is acceptance for w signal events , @xmath29 is the w reconstruction and selection efficiency , and @xmath30 is the integrated luminosity . while acceptance has to be estimated with mc , the lepton reconstruction and selection efficiency can be derived directly from data with a tag - and - probe method @xcite . the expected statistical error of the measured cross section is 1.5% for an integrated luminosity of 10 pb@xmath21 . the systematic error is expected to be dominated by the luminosity error , which is expected to be about 10% at the cms start - up @xcite . similarly the inclusive z boson production is another `` standard candle '' to help us commision cms for physics . cms studied experimental sensitivities to the inclusive z boson cross section in both di - muon and di - electron decays @xcite . comparing to the @xmath31 analysis , due to presence of two isolated high-@xmath4 leptons the background was expected to be less than one percent after final event selection . the major background contributions were from qcd dijet , w plus jets , @xmath16 , @xmath32 . figure [ fig : zxsec ] shows the reconstructed @xmath33 invariant mass distribution for an integrated luminosity of 10 pb@xmath21 . both expected signal and background contributions are shown . the final @xmath34 sample was selected from events with 70 gev @xmath35110 gev . the cross sections were obtained after correcting for efficiencies and acceptance following eq . [ eq : xsec ] . the expected cross section for @xmath36 decays as a function of statistics corresponding to different luminosity scenarios is also shown in fig . [ fig : zxsec ] . the results were normalized to the cross section determined with a mc sample corresponding to an integrated luminosity of 133 pb@xmath21 . the expected statistical error at 10 pb@xmath21 of integrated luminosity is about 2% . both analyses showed similar sensitivities . the 10% luminosity uncertainty is again expected to dominate the total error . the large w / z cross sections at the lhc makes high - precision differential measurements possible . cms performed a measurement of the muon differential cross section measurement as a function of muon pseudorapidity in inclusive @xmath12 production @xcite . this analysis utilized the same trigger path as the inclusive @xmath20 cross section analysis . the @xmath12 candidates were selected with muon @xmath37 gev and met@xmath3820 gev . a calorimeter - based isolation was used to suppress the qcd dijet contribution . after correcting for efficiencies and acceptance , the expected muon pseudorapidity distributions at an integrated luminosity of 10 pb@xmath21 are shown in fig . [ fig : muondiffxsec ] . the pdf error on the experimental data points is the theoretical error in estimating acceptance . among other systematic errors , the 10% luminosity error dominates . the results were compared to theoretical predictions from pythia . we estimated the pdf error using the cteq6 m @xcite pdf model with pdf - reweighting technique @xcite . with 10 pb@xmath21 of integrated luminosity , the results are still dominated by experimental systematic error . to minimize experimental systematic errors , cms also studied the muon charge asymmetry defined in eq . [ eq : asym ] because many experimental errors cancel out . the pdf error on this quantity is only at few percent level @xcite . the analysis strategy was identical to the muon differential cross section analysis described above . we computed the observed charge asymmetry , @xmath39 , with background subtracted number of @xmath12 signal events , @xmath40 , @xmath41 assuming that reconstruction and selection efficiency ratios between @xmath42 and @xmath43 are one . because of the weak decay of w bosons , the acceptance ratio between @xmath42 and @xmath43 differs from unity . in this analysis , we did not correct for the acceptance difference in @xmath39 but absorbed it into the theoretical predictions . the charge asymmetry as a function of muon pseudorapidity for an integrated luminosity of 100 pb@xmath21 is shown in fig . [ fig : wasym ] @xcite . the result is compared to theoretical predictions from pythia , where the pdf error was estimated with cteq6 m pdf model . the systematic error is dominated by the statistical error on the efficiency ratio between @xmath42 and @xmath43 determined using 100 pb@xmath21 of drell - yan mc . even with a conservative treatment of systematic errors , the total errors of this measurement are comparable to the pdf errors and potentially could provide new constraints on different pdf models . of simulated luminosity . the systematic error is dominated by the statistical error on the efficiency ratio between @xmath42 and @xmath43 determined using 100 pb@xmath21 of drell - yan mc . , width=302 ] the z boson differential cross section as a function of z rapidity can also be used to test higher order perturbation calculations and put constraints on pdf models . cms performed a study of this observable using @xmath44 events @xcite . to remove the luminosity uncertainty in this measurement , the following observable was studied , @xmath45 where for each bin @xmath46 of rapidity ( @xmath47 ) , @xmath48 is the number of background subtracted @xmath44 candidates , @xmath49 is the bin width , and @xmath50 is the product of the efficiency and acceptance for detecting and reconstructing a z boson with rapidity @xmath47 . with conventional electron reconstruction at the cms , where both cms ecal and tracking system are utilized , the coverage for electrons is up to pseudorapidity of about 2.5 . the reconstructed @xmath44 candidates can be used to directly probe partons with kinematics , where @xmath51 is the center of mass energy at the lhc . ] outside the range of previous experiments @xcite . the kinematics reach was further extended by using electrons reconstructed using the cms forward hadronic ( hf ) calorimeter @xcite , which has a coverage up to pseudorapidity of 4.6 . the shower shape of hf reconstructed electron candidates was utilized to remove @xmath44 background events effectively . the final results for the rapidity measurement for an integrated luminosity of 100 pb@xmath21 is shown in fig . [ fig : zeeshape ] . the background in the hf region is well under control . the expected measurements are compared to predictions with cteq6.1 pdf model @xcite . with an integrated luminosity of 100 pb@xmath21 , we are expecting to provide new constraints on different pdf models . cms performed mc studies to explore w / z boson production with initial lhc data . with 10 pb@xmath21 of integrated luminosity , the inclusive w / z cross sections could be established with 1 - 2% statistical precision . however , it is expected that the luminosity uncertainty will dominate the total error in these measurements . the sensitivities to constrain different pdf models at cms were also explored using measurements of the muon charge asymmetry in inclusive @xmath52 process and the z rapidity shape in inclusive @xmath33 process . with about 100 pb@xmath21 of integrated luminosity , both measurements could provide constraints on different pdf models . we thank the technical and administrative staff at cern and other cms institutes , and acknowledge support from : fmsr ( austria ) ; fnrs and fwo ( belgium ) ; cnpq , capes , faperj , and fapesp ( brazil ) ; mes ( bulgaria ) ; cern ; cas , most , and nsfc ( china ) ; colciencias ( colombia ) ; mses ( croatia ) ; rpf ( cyprus ) ; academy of sciences and nicpb ( estonia ) ; academy of finland , me , and hip ( finland ) ; cea and cnrs / in2p3 ( france ) ; bmbf , dfg , and hgf ( germany ) ; gsrt ( greece ) ; otka and nkth ( hungary ) ; dae and dst ( india ) ; ipm ( iran ) ; sfi ( ireland ) ; infn ( italy ) ; nrf ( korea ) ; las ( lithuania ) ; cinvestav , conacyt , sep , and uaslp - fai ( mexico ) ; paec ( pakistan ) ; scsr ( poland ) ; fct ( portugal ) ; jinr ( armenia , belarus , georgia , ukraine , uzbekistan ) ; mst and mae ( russia ) ; mstds ( serbia ) ; micinn and cpan ( spain ) ; swiss funding agencies ( switzerland ) ; nsc ( taipei ) ; tubitak and taek ( turkey ) ; stfc ( united kingdom ) ; doe and nsf ( usa ) . individuals have received support from the marie - curie ief program ( european union ) ; the leventis foundation ; the a. p. sloan foundation ; the alexander von humboldt foundation . 9 collaboration , m. banner _ et al . b * 122 * , 476 ( 1983 ) . collaboration , g. amison _ et al . b * 126 * , 398 ( 1983 ) . et al . _ , jinst * 3 * s08001 ( 2008 ) . campbell , j.w . huston , and w.j . stirling , rept . . phys . * 70 * 89 ( 2007 ) . c. anastasiou _ et al . _ , d * 69 * , 094008 ( 2004 ) . collaboration , jinst * 0803 * s08004 ( 2008 ) . t. sjostrand _ et al . _ , comput . . commun . * 135 * 2001 . j. pumplin _ et al . _ , arxiv : hep - ph/0201195 . s. agostinelli _ et al . instrum . methods . a * 506 * 250 ( 2003 ) . collaboration , cms - pas - ewk-09 - 001 ( 2009 ) . collaboration , cms - pas - ewk-09 - 004 ( 2009 ) . collaboration , cms - pas - ewk-07 - 002 ( 2007 ) . et al . _ , arxiv : hep - ph/0903.3861 . collaboration , cms - pas - ewk-09 - 003 ( 2009 ) . j. pumplin _ et al . _ , jhep * 0207 * , 12 ( 2002 ) . d. bourilkov , r. group , and m. whalley , arxiv : hep - ph/0605240v2 . a.m. cooper - sarkar , talk in pdf4lhc workshop ( 2009 ) . collaboration , cms - pas - ewk-09 - 005 ( 2009 ) . g. baiatian _ et al . j. * c53 * 139 ( 2008 ) . s. kretzer _ et al . d. * 69 * , 114005 ( 2004 ) .

at the lhc , the production cross sections of w / z bosons are tens to hundreds of nanobarns . the production mechanism of these processes is well established in the standard model and these processes can be used as `` standard candles '' to help commission the cms detector for physics . leptonic decays of w / z bosons are expected to have very high trigger efficiency and signal to background ratio . therefore they are ideal channels to study the properties of w / z bosons in detail , such as cross sections and charge asymmetry . in this paper early cms results on inclusive w / z production at 10 tev center - of - mass energy are discussed .

various protein protein interaction inhibitors ( ippis ) are in development to treat cancer , neurodegenerative disease , autoimmune disease , arthritis , viral infection , bacterial infection , etc . , and several have advanced into clinical trials and beyond . historically , ppi interfaces have been considered comparatively intractable drug targets for typical drug - like molecules . but over the past decade , several approaches including screening of natural product - like compounds , mimicry of protein interfaces , and fragment - based drug discovery ( fbdd ) have offered tangible success . fbdd allows for the identification of small weakly binding chemical fragments , which can be subsequently linked or extended into unique multi - fragment scaffolds . fragment - based approaches have led to the discovery of several high - affinity inhibitors that are highly complementary to the distinct ppi interfaces they target , and the tightest binders attain picomolar affinities . alanine scanning mutagenesis is commonly used to identify residues that interact most favorably in a ppi complex . these interactions , between individual hot spot residues and the partner protein , are reminiscent of a fragment - centric view of the ppi interface . clusters of hot spot residues can serve as promising starting points for the design of small molecule ippis , and biomimetic ippis are often designed specifically to preserve these hot spot interactions and to optimize them . while identification of the important side chains can provide a good starting point for ppi inhibitor design , alanine scanning does not provide structural information about the surface involved in a hot spot interaction or the degree of complementarity between the surface and the side chain binding fragment . thus , from an inhibitor design perspective , whether using fbdd or the alanine scanning technique , it is of significant interest and importance to obtain fragment - centric structural mapping of the target interfaces . mapping of ppi interfaces is closely related to the problem of ligand binding site detection . over the years , a number of diverse algorithms have been developed for this purpose , which fall into four general categories : geometry - based , probe - based , grid - based , and docking - based . some methods rely on the structure alone , while others incorporate energetic terms or sequence conservation into the pocket detection . examples from all categories perform strongly when detecting classical ligand binding pockets , which are often large isolated cavities in the protein surface with well - defined concavity . some of these methods have been applied to investigate ppi interfaces , such as q - sitefinder ( a grid - based pocket detection method ) , ftmap ( a docking - based solvent - mapping method ) , and findbindsite ( a ligand / fragment - docking - based method ) , all of which reveal that ppi interfaces are not adequately described by a single cavity , but comprise multiple interaction regions . on the other hand , the grid- and structure - based method dogsite has applied the concept of subpockets to demonstrate that a higher - resolution characterization of classical ligand binding pockets is generally feasible and practical , however this approach has yet to be applied to ppi interfaces . because ppis often feature large and flat binding surfaces , without the deep pockets of typical drug targets , they pose a distinct challenge for geometry - based pocket - detection methods in providing a meaningful fragment - centric structural characterization . for example , the application of three popular geometry - based methods ( castp , fpocket , and single linkage clustering similar to sitefinder ) to characterize two established druggable ppi interfaces mdm2/p53 and bcl - xl / bak results in inconsistent definitions of pocket profiles ( see figure s1 ) . the results do not represent the fragment - centric interactions observable at the interfaces and suggest a limited utility of the methods from a fbdd perspective . we observe three specific limitations : incomplete interface coverage , pocket expansion into solvent - inaccessible regions , and overconsolidation of pocket space across multiple side chain interactions , which lowers the resolution of the interfacial characterization . in order to address the above limitations , we have developed alphaspace , a new computational analysis tool that features a fast geometry - based approach to provide a comprehensive fragment - centric topographical mapping of the ppi interface . alphaspace follows in the footsteps of fpocket and moe s sitefinder by using alpha spheres , a geometric feature of a protein s voronoi diagram , to map out concave interaction space at the surface of a protein . prior to these , the application of voronoi tessellation to cavity detection originated in the pioneering work of liang et al . and was first implemented in the cast program . however , alphaspace is unique among these existing voronoi - based methods in its general divergence from a cavity - centric paradigm toward a fragment - centric and full - surface paradigm . central to our approach are two new features , alpha - atom and alpha - space , and the new concept of the alpha - atom / alpha - space pair , which we utilize to rank interaction regions for fragment - targetability and to evaluate pocket / fragment complementarity to guide fragment optimization . additional alphaspace components , including pocket matching and pocket communities , extend the fragment - centric methodology to establish a flexible pocket model and to identify highly targetable protein surface regions . in the following sections , first , we present the methodology behind alphaspace fragment - centric topographical mapping ( fctm ) and highlight aspects that enable alphaspace to reveal the fragment - centric modularity at ppi interfaces and to quantitatively evaluate fragment - centric pockets . for the initial section of the results , we apply fctm to the well - studied mdm2/p53 ppi interface , discussing the utility of fragment - centric inhibitor design features . fctm results are compared with the corresponding interaction regions detected using fpocket and ftmap . in the second section of the results , we evaluate the performance of alphaspace on a larger data set of 12 ppi , 12 ippi , and 9 apo structures from the 2p2i database . finally , we discuss a more general perspective on the alphaspace methodology and present conclusions . the central geometric construct employed by alphaspace is alpha sphere , a geometric feature derived from the voronoi diagram of a set of points in three - dimensional space . the voronoi diagram is a tessellation of the space containing the points into a set of voronoi cells , or polyhedrons , formed from planes that bisect adjacent points from the set . each alpha sphere center will be an intersection of six bisecting planes and equidistant to exactly four points from the set . the concept of applying voronoi tessellation to protein structure was first introduced by richards in 1974 , along with the weighted voronoi tessellation , a variation in the calculation to account for different atomic radii that was later implemented by liang et al . in cast . alphaspace employs the classical voronoi tessellation , also used by fpocket , for which all atoms are treated as equivalent points . in this case , the alpha sphere makes contact with the centers of exactly four atoms but is otherwise empty of other atomic centers . alpha spheres centered outside the protein surface mark concave surface regions and can be used to represent potential interaction space . figure 1a illustrates how a voronoi diagram can be used to map the concave interaction space in a two - dimensional schematic model of shallow pockets in a surface . ( a ) two - dimensional schematic of two fragment - centric pockets in a protein surface . the delaunay triangulation for one pocket is shown in purple ; its total contiguous area ( or volume , in 3-dimensions ) is the total alpha - space for that pocket and is used to calculate pocket score . ( b ) an individual alpha - system : alpha sphere ( orange ) , alpha - atom ( blue ) , alpha - space ( purple ) , and contact atoms ( gray ) . ( c ) an individual alpha - system in three - dimensions , colored as in ( b ) . with alphaspace , we introduce two additional alpha sphere - related geometric features : alpha - atom and alpha - space ( figure 1b , c ) . an alpha - atom shares a center with its associated alpha sphere but with a reduced radius set to 1.8 . an alpha - atom can be thought of as a theoretical ligand atom at a discrete interaction point , positioned to make approximate contact with the small region of protein surface associated with the set of four alpha sphere contact atoms . the alpha - space is the volume of the tetrahedron defined by the centers of the four alpha sphere contact atoms . every alpha - atom has an associated alpha - space , the volume of which captures information about the relative positions of the four contact atoms , which is related to the structure of the surface region associated with these four atoms . the set of all alpha - spaces for a set of points is equivalent to its delaunay triangulation , the dual graph of the voronoi diagram . alphaspace fragment - centric topographical mapping ( fctm ) is performed in two stages : pocket identification and pocket evaluation , as shown in figure 2 . overview for the two stages of fragment - centric topographical mapping ( fctm ) . stage 1 : pocket identification alpha sphere detection : all alpha sphere centers are shown and colored by radius ( orange , r < 3.2 ; yellow , 3.2 < r < 5.4 ; green , r > 5.4 ) . alpha sphere filtration : remove alpha spheres outside the minimum or maximum radius cutoffs . alpha sphere clustering : alpha spheres are clustered into fragment - centric pockets ( colored by alpha - cluster ) . alpha - cluster selection : only alpha - clusters in contact with the peptide or ligand are selected for evaluation ( alternatively the selection can be expanded to include unoccupied pockets near the interface ) . stage 2 : pocket evaluation includes pocket ranking by alphaspace pocket score , pocket - fragment complementarity to evaluate the percentage occupation of each pocket , pocket matching between different structures of the protein , and pocket communities to identify potentially druggable surface regions . the first stage , pocket identification , consists of four consecutive steps : i.alpha sphere detection . all alpha spheres are identified from the voronoi tessellation of a protein structure . we employ the python wrapper to qhull , available in the scipy package , to calculate the voronoi diagram.ii.alpha sphere filtration . identified alpha spheres are filtered by radius to remove from the analysis spheres deemed too small to represent solvent - accessible space ( 3.2 is set as the default minimum radius cutoff , figure s2c ) or too large to accurately represent space within contact proximity of the protein surface ( 5.4 is set as the default maximum radius cutoff , figure s2b ) . these filtration parameters , which deviate from the corresponding default parameters in fpocket ( 3.0 and 6.0 , respectively ) , have been optimized to restrict our mapping to include only solvent - accessible space near the surface of the protein.iii.alpha sphere clustering . remaining alpha spheres are clustered into pockets , or alpha - clusters , using an average linkage algorithm to restrict individual pocket size to represent small , fragment - centric interaction spaces.iv.alpha-cluster selection . pockets at the ppi interface , or within an expanded interface , are then selected for subsequent quantitative evaluation . all alpha spheres are identified from the voronoi tessellation of a protein structure . we employ the python wrapper to qhull , available in the scipy package , to calculate the voronoi diagram . are filtered by radius to remove from the analysis spheres deemed too small to represent solvent - accessible space ( 3.2 is set as the default minimum radius cutoff , figure s2c ) or too large to accurately represent space within contact proximity of the protein surface ( 5.4 is set as the default maximum radius cutoff , figure s2b ) . these filtration parameters , which deviate from the corresponding default parameters in fpocket ( 3.0 and 6.0 , respectively ) , have been optimized to restrict our mapping to include only solvent - accessible space near the surface of the protein . alpha sphere clustering . alpha - clusters , using an average linkage algorithm to restrict individual pocket size to represent small , fragment - centric interaction spaces . alpha - cluster selection . pockets at the ppi interface , or within an expanded interface , are then selected for subsequent quantitative evaluation . in comparison with fpocket and moe s site finder , the main deviation of alphaspace within this pocket identification stage is in the third step , alpha sphere clustering , where we employ an average linkage algorithm with an optimized clustering parameter to achieve a fragment - centric mapping . because of the subtlety in fragment - centric structural modularity at ppis , there is often not a well - defined gap within the flow of alpha spheres across the surface . this is why fpocket s multi - step clustering algorithm ( which includes a multiple linkage step set to 2 by default ) and sitefinder s single linkage clustering algorithm are observed to extend individual pocket space across multiple fragment or side chain interactions ( figure s1 ) . alphaspace , alternatively , clusters filtered alpha spheres into localized pockets , or alpha - clusters , using the average linkage routine in the scipy hierarchical clustering package . the algorithm uses the pairwise alpha sphere euclidian distance matrix to generate a dendrogram according to the average - linkage criterion ( figure s3 ) . the clustering parameter , which is the maximum mean distance between elements of any single cluster , determines where to cut this tree and , thus , the general size and final number of alpha - clusters in the topographical map . here , by considering amino acid side chains to be the natural binding fragments in ppis , we fit this clustering parameter to yield , on average , one alpha - cluster for every side chain engaged in a ppi . as shown in figure s4 , the average number of side chains per pocket is near unity when the maximum average linkage distance is within the range 4.6 to 4.8 . besides the third clustering step , the fourth step , alpha - cluster selection , also marks a conceptual break from the fpocket algorithm . fpocket , as a more classical cavity - centric pocket detection method , aims to identify the most significant individual pockets as probable enzymatic active sites or ligand binding pockets . this leads to incomplete coverage for ppi interfaces , where many of the interactions involve smaller and shallower fragment - centric pockets . alphaspace , alternatively , does not screen pockets by number of alpha spheres but detects contact with the molecular binding partner to select for the array of alpha - clusters engaged in the ppi . this provides a landscape - like topographical map with extensive coverage of the interaction interface . furthermore , in alphaspace , adjacent interaction regions are represented simultaneously as discrete alpha - clusters and as overlapping pockets , with shared pocket atoms along their boundaries . we leverage this pocket overlap to moderate the expansion of interface contact maps to reveal unoccupied targetable pockets near interaction interfaces . selected pockets from the first stage the analysis includes pocket ranking , pocket - fragment complementarity , pocket matching , and pocket communities , as illustrated in figure 2 . pocket evaluation is facilitated by the alpha - atom and alpha - space features and provides a high - resolution map of underutilized and targetable pocket space at a ppi interface . we use alpha - space as a geometric feature related to the size and shape of a localized region of protein surface . the size of an individual alpha - space reflects the surface area and curvature of the small surface region associated with the set of four alpha sphere contact atoms ( figure 1 ) . while the set of alpha spheres in an alpha - cluster will overlap , the corresponding set of alpha - spaces will fit face - to - face to form a contiguous volume . this allows for the sum over all alpha - spaces within a pocket to serve as a single metric that approximates the surface area and curvature of the complete pocket . figure s5 illustrates the geometric relationship between the alpha - atom and the alpha - space in the context of an alpha - cluster ( the trp92 pocket from mdm2/p53 ) . the alpha - atom construct can be used to calculate the alpha - cluster contact surface area ( acsa ) for each individual pocket . when alpha spheres are clustered to define a pocket , the corresponding alpha - atoms form an overlapping alpha - cluster , the outline of which represents the approximate shape and size of that pocket s complementary pseudofragment ( figure 3 ) . to calculate the atomistic acsas for an individual pocket , we use naccess to calculate the atomistic accessible surface areas for the protein structure alone and then for the same protein in complex with that pocket s single alpha - cluster . subtracting the atomistic values associated with the alpha - cluster complex from the corresponding atomistic values associated with the protein alone will yield non - zero ( and positive ) values only for the set of atoms in direct contact with the alpha - cluster . these differences are taken as the atomistic surface areas associated with that individual pocket . ( a ) two - dimensional schematic depicting components used to calculate pocket score ; solvent probes ( yellow ) and alpha - atoms ( blue ) are used to calculate the alpha - cluster contact surface area ( acsa ) ( black ) of the pocket atoms ( gray ) . below , alpha - atom and alpha - space representations for a low - scoring , shallow pocket ( b ) and for a high - scoring , deep pocket ( c ) . given a pocket j , we calculate its pocket score with the following formula : where is an alpha - space within pocket j with volume v , acsai , j is the alpha - cluster contact surface area for atom i calculated using alpha - cluster j ( for each alpha - space we sum over the four corresponding alpha sphere contact atoms ) , and npi , j is the binary polarity status for atom i in pocket j ( 1 for nonpolar atoms and 0 for polar atoms ) . conceptually , the pocket score is equivalent to the pocket s nonpolar - weighted alpha - space volume . the score was developed as a single term to correlate well with a combination of nonpolar surface area and pocket curvature , two structural / chemical features previously shown to reflect a pocket s maximal binding potential . pocket score development details are described in the supporting information , section s4 , and figures s1214 . if pocket j is engaged in a ppi or ippi , we assess the structural complementarity between the pocket and the bound chemical fragment with the following formula : where % occj is the percentage of the interaction space of pocket j that is occupied by the bound ligand , is an alpha - space within pocket j with volume v , and o is the binary occupation status of ( 1 if occupied and 0 if unoccupied ) . conceptually , we are partitioning the total alpha - space of the pocket into occupied space and unoccupied space by leveraging the discrete nature of each alpha - atom / alpha - space pair . thus , the alpha - space occupation status is mediated through the position of its corresponding alpha - atom . alpha - space occupation is conferred by spatial overlap between its alpha - atom and an atom from the bound ligand molecule , evaluated using a 1.6 cutoff distance measured between the centers of the alpha - atom and the ligand atoms . carbon bond length so that an unoccupied alpha - atom should represent a targetable interaction space , able to accommodate at least a methyl extension to the ligand , given the proper structure and chemistry of the evolving ligand . in order to match similar fragment - centric pockets among different structures of the same protein , we calculate an n n distance matrix , where n is the total number of interface pockets among all structures included in the matching . pocket matching can be applied to any number of structures collectively . to calculate a pairwise pocket distance , dj , k , between pockets j and k , we represent each pocket s acsa as an array of length i , where i is the total number of heavy atoms found in the protein structure , containing the i atomistic acsas for each pocket this vector will be non - zero only for the set of atoms in contact with that pocket s alpha - cluster . our distance metric is inspired by the jaccard distance , a statistic used for evaluating the dissimilarity between sample sets , and is implemented aswhere the sum of all nonshared acsa between pocket j and pocket k is divided by the total acsa of pocket j and pocket k. this formula approximates the portion of the total pocket surface area that is dissimilar between the two pockets ; values will range from 0 , the distance between two identical pockets , to 1 , the distance between two pockets with zero shared atoms . additionally , for every pair of pockets from the same structure , the pocket distance is artificially set to a large value of 10 , which is to avoid matching pockets within the same structure . from the calculated pairwise pocket distance matrix , the average linkage hierarchical clustering approach is employed to decompose all pockets into clusters , for which the distance clustering parameter is set to 0.75 by default . all pockets within one cluster are considered to be matched , and the pairwise pocket similarity , sj , k , is evaluated as 1 dj , k . this pocket matching approach serves as the foundation for an alignment - free flexible pocket model , a concept previously explored by eyrisch and helms to track pockets across a molecular dynamics trajectory . a pocket cluster defines a flexible pocket entity , in which the mutual similarity describes an intrinsic degree of structural integrity , while differences among individual pockets within the cluster indicate structural flexibility . druggable ppi interfaces are typically defined by multiple fragment targetable interaction regions in close proximity , which often include one or several particularly important anchor interactions . inspired by this anchor / satellite interaction concept , we have developed a pocket community feature to detect potentially druggable protein surface regions . first , all quantified pockets are classified as core , auxiliary , or minor pockets by employing alphaspace pocket score , for which the core and auxiliary pocket score cutoffs are set to 100 and 30 by default . then core pockets serve to initiate pocket communities ; each isolated core pocket or each set of overlapping core pockets is designated as a community core . each expanded set of core and auxiliary pockets is designated as a pocket community . this protocol does allow for pocket overlap between distinct communities ; overlapping communities are not consolidated . to qualify as overlapping pockets in both core pocket consolidation and auxiliary pocket expansion a pair of pockets must satisfy two requirements : ( 1 ) share at least one pocket atom and ( 2 ) if the pockets point away from each other , the angle between their directional pocket vectors can not be greater than 90. the second requirement strengthens the prediction of pocket community cotargetability ; this is included to avoid grouping together pockets that do share atoms but face opposite directions . a pocket s directional vector , a novel alphaspace descriptor , is defined from the centroid of its pocket atoms to the centroid of its alpha - cluster . the community score , which is the sum of all pocket scores ( core and auxiliary ) within a community , can be used to help detect potentially druggable protein surface regions . we first utilized the well - studied mdm2/p53 ppi as a test case to retrospectively demonstrate how alphaspace fragment - centric topographical mapping ( fctm ) can be employed to facilitate rational ppi inhibitor design . the mdm2/p53 ppi offers an attractive model because of the availability of high - resolution structures for the native ppi as well as for mdm2 bound to a biomimetic inhibitor , bound to a small molecule fragment - based inhibitor , and in the apo protein state . we evaluate the ability of alphaspace to identify hot spot - associated pockets at the four interfaces and to detect and match important auxiliary interaction regions . we then evaluate the application of alphaspace to a larger data set of 12 ppi , 12 ippi , and 9 apo structures from the 2p2i database ; this data set was curated to represent systems successfully targeted by and crystallized with small molecule ppi inhibitors . we confirm that high - ranking fragment - centric pockets are generally enriched at ppi and ippi interfaces , which we leverage using pocket communities to identify the ippi interfaces from surface structures alone . we demonstrate that pocket matching between sets of ppi / ippi / apo protein structures allows us to identify and track similar pockets at a fragment - centric resolution to measure pocket flexibility and to characterize the structural integrity of the surface at functional interfaces . mdm2/p53 is an important ppi and oncogene drug target , with several small molecule inhibitors currently in clinical trials . its ppi interface is formed between a 13-residue helical section from the n - terminal transactivation domain of p53 and a well - defined binding groove in the surface of mdm2 . this interaction is known to be anchored by three primary hot spot residues from p53phe19 , trp23 , leu26and a secondary hydrophobic interaction with leu22 . as shown in figure 4 , alphaspace fctm detects a total of seven contact pockets in the surface of mdm2 at the mdm2/p53 interface . aside from pocket 3 , which is occupied by the side - chains of leu26 and pro27 , and pocket 5 , which interacts with the backbone of p53 , the other five pockets each clearly contact a single side chain from p53 . there is a distinct spatial overlap between the alpha - cluster centroids and the pocket - bound peptide fragments . this indicates an innate structural modularity in the protein surface that reflects the corresponding side chain interactions . it should be noted that such a complete and fragment - centric characterization of the mdm2/p53 interface was not achieved using fpocket with the default parameters . as shown in figure s1b , the corresponding fpocket analysis detects a single pocket in the surface of mdm2 at the mdm2/p53 interface , spanning the trp23 , leu26 , and pro27 interactions , and does not account for the important mdm2 interactions with phe19 or leu22 of p53 . alpha - space - based pocket features are presented for the seven contact pockets at the mdm2/p53 ppi interface . ( a , b ) different visual representations of the fctm result for mdm2/p53 . ( a ) interface pockets are represented by the centroid of each alpha - cluster . the side chains from p53 are displayed and labeled whenever they make contact with one of the interface pockets , and pocket - fragment interactions are color - coordinated . the natural modularity of the surface is exhibited in the overlap between the centroids and the side chains . ( b ) each pocket is represented as a surface , alpha sphere centers are shown as small spheres colored by pocket , and the alpha - cluster centroids are depicted as large transparent spheres . for the seven alphaspace pockets , the calculated pocket features pocket score , percent occupied , total alpha - space , and percent nonpolar are presented in figure 4 . we find that pocket 1 ( score = 241 ; 72% occupied ) and pocket 2 ( score = 189 ; 94% occupied ) engage the two essential hot spot residues trp23 and phe19 of p53 , respectively . the less occupied pocket 3 ( score = 154 ; 33% occupied ) these results are consistent with the experimental alanine - scanning data for p53 , as shown in table s2 , in which mutation of either phe19 or trp23 reduces the mdm2/p53 binding affinity below the detectable limit and leu26/ala mutagenesis results in a significant reduction of binding affinity by more than 50 fold . meanwhile , the leu22 of p53 , whose alanine mutagenesis results in a 10-fold decrease in mdm2/p53 binding affinity , interacts with the lowest ranked pocket 7 ( score = 12 ; 100% occupied ) . the targeting of a low - scoring pocket by an important residue underscores that a truly complete pocket analysis depends on the surface mapping of both binding partners . either surface may simultaneously function as both pocket and ligand , even for a helix - in - groove ppi such as mdm2/p53 . when we , inversely , map the surface of the p53 helix , we find leu22 is involved in the formation of the most significant p53 pocket ( score = 37 , 75% occupied ) , which , in the complex , binds val69 from mdm2 ( figure s6 ) . thus , in targeting a small auxiliary pocket , leu22 also completes the formation of an important interaction region on p53 , enriching the quality of the total ppi interaction . the values for several other pocket - centric and ligand - centric descriptors are listed in table s3 , including atom counts , polar atom counts , presence of charged species , and the residue ids of the contact fragments . additionally , results for the fctm of a second well - studied system , the bcl - xl / bak ppi interface , are presented in the supporting information . table s5 reports the experimental alanine scanning data for the bak helical interaction domain . figure s16 illustrates the fctm of the bcl - xl surface at the ppi interface . again , structural modularity can be observed in the overlap between the interacting side chains of bak and the alpha - cluster centroids . leu78 and ile85and the two moderately high scoring pockets correspond to two of the three secondary bak hot spots val74 and ile81 . ( the final secondary hot spot asp83extends into the solution , away from the ppi interface . ) the additional pocket - centric and ligand - centric features for bcl - xl / bak are presented in table s6 . the mdm2/p53 interface has been effectively targeted using both fragment - based and biomimetic inhibitor design . the nutlins , a set of cis - imidazoline small molecules that mimic the four main interaction points , were the first inhibitors discovered to modulate mdm2/p53 . subsequent fbdd efforts led to the discovery of the current ultrahigh affinity inhibitors that optimize these primary interactions and introduce additional , novel interaction points . we have selected two ippi structures of mdm2 in complex with ultrahigh - affinity inhibitors emerging from each of these design strategies : a small fragment - based molecule ( a piperidinone sulfone derivative ) with ic50 0.10 nm ( pdb : 4oas ) and a d - peptide antagonist ( pmi- ) with kd 0.22 nm ( pdb : 3tpx ) . figure 5 displays the mapping of each of these interfaces , along with those of the native mdm2/p53 ppi ( pdb : 1ycr ) and the apo state of mdm2 ( pdb : 1z1 m ) . this mdm2/p53 map has been expanded to include unoccupied pockets near the interface in addition to p53 contact pockets . the same interface atom list from mdm2/p53 was used to select for pockets in the apo structure . pocket matching is performed on the four mdm2 structures collectively , and the result is presented in figure 5 . ( a ) mdm2/p53 , ( b ) mdm2 apo , ( c ) mdm2/pmi- ( d - peptide inhibitor ) , and ( d ) mdm2/piperidinone sulfone derivative ( small molecule inhibitor ) . topographical maps of the interfaces are illustrated ; matching pockets are color coordinated and numbered . circled in ( a ) are three unoccupied pockets identified near the ppi interface . pockets circled in ( c ) and ( d ) match with the unoccupied pockets from ( a ) but are now targeted by inhibitor fragments . the table presents the matching results for all pockets , including similarity ( calculated in reference to the matching mdm2/p53 pocket ) , pocket score , and percent pocket occupation . in the development of these picomolar inhibitors , mirror image phage display with chemical ligation and fragment - based screening methods led to the identification of three auxiliary interaction sites in the vicinity of the mdm2/p53 interface but not utilized in the native mdm2/p53 ppi . these are an acetate fragment binding region adjacent to the leu22 interaction site ( targeted by both inhibitors ) , a hydrophobic patch on the opposite side of the helix between the trp23 and leu26 binding pockets ( targeted by pmi- ) , and the glycine shelf , which is adjacent to the phe19 binding pocket ( targeted by the small molecule inhibitor ) . fctm of these interfaces not only identifies each of these interaction regions as distinct pockets in the corresponding ippis , but identifies all three interaction regions as unoccupied pockets in the native mdm2/p53 interface : pocket 7 , pocket 10 , and pocket 6 , respectively ( figure 5a ) . the targeting of pocket 7 , despite its low pocket score , significantly enhances the affinity of both inhibitors by introducing favorable electrostatic interactions between the acetate fragment and lys94 , his96 , and , for pmi- , his73 . the affinity enhancement due to this fragment is roughly 20-fold for the small molecule inhibitor and , for pmi- , a predecessor to pmi- , the alanine mutation of this acetate side chain reduces affinity by about 10-fold . for pmi- , the alanine mutation of the leu10 , which targets pocket 10 , reduces affinity by 4.5-fold . pocket 10 has a particularly low pocket score , but , as with leu22 of p53 discussed above , the targeting of this pocket forms a reciprocal pocket in the surface of pmi- ( score = 40 ) that is filled by leu54 from mdm2 ( figure s7 ) . the specific affinity enhancement due to the targeting of pocket 6 by the tert - butyl fragment of the small molecule inhibitor is difficult to assess independently since this fragment and the ethyl fragment occupying pocket 2 were modified in tandem , but the initial targeting of this pocket in the development of its predecessor , am-8553 , enhanced affinity about 20-fold . overall , this indicates that the targeting of small , auxiliary pockets , detectable using alphaspace , can facilitate the productive design of competitive ppi inhibitors . the top three pockets from the mdm2/p53 interface are associated with the primary hot spot residues from p53 and can be matched with three similar pockets from the ippi interface between mdm2 and the ultrahigh - affinity small molecule inhibitor ( figure 6 ) . using pocket - fragment complementarity , we measure improvements for all three pockets between the native ppi and the optimized ippi . for pocket 1 and pocket 3 , by individually aligning the matching pockets using the positions of shared pocket atoms , we can visualize the spatial relationship between the unoccupied subspace detected in the native ppi and the corresponding occupied space in the ippi . from the alignment of pocket 1 , we observe the phenyl ring from the 4-chlorophenyl inhibitor fragment is aligned with the six - member ring of trp23 . the chloro fragment on the inhibitor extends directly into the unoccupied space identified near trp23 , and the pocket - fragment complementarity improves from 72% occupied in the ppi to 95% occupied in the ippi . for pocket 3 , occupation is only 33% in the ppi ; neither of the interacting residues ( leu26 , pro27 ) is optimally positioned to extend into the core of the pocket , leaving considerable unoccupied interaction space . alternatively , the 3-chlorophenyl fragment from the inhibitor approaches the pocket from a different angle , and the halogen extends directly into the space unoccupied in the ppi , boosting pocket occupation to 98% . regarding pocket 2 , the conservation of high pocket - fragment complementarity between the ppi and the ippi ( 94% and 100% respectively ) is a good example of functional pocket flexibility . this pocket , expanded in the ppi to accommodate the bulky side chain of phe19 , collapses significantly in the ippi in response to the smaller ethyl fragment , retaining complementarity with the ligand . as highlighted in figure 7 , the structural mechanism for this pocket flexibility is driven primarily by loop dynamics . pocket alignments between mdm2/p53 ( ppi ) and mdm2/small molecule inhibitor ( ippi ) for pockets 1 ( center ) , 2 ( right ) , and 3 ( left ) . ppi : pockets ( gray ) , alpha - centers ( light gray ) , and bound residues ( dark gray ) . ippi : pockets ( pink , green , yellow ) , alpha spheres ( pink , green , yellow ) , and bound fragments ( red ) . in the top panels , we specify the score and the percent occupation for each pocket in the color - coded top bars . in the bottom panels , we specify the calculated similarity for each pocket pair , and we specify the bound residues from the native ppi and the bound chemical fragments from the ippi . residue - centric visualization of flexible pocket 2 at the mdm2/p53 ppi ( a ) and the mdm2/small molecule inhibitor ippi ( b ) . pocket defining residues are shown in stick representation , labeled , and colored light purple if structurally stable or magenta if structurally variant between pockets . the peptide fragment ( a ) and inhibitor fragment ( b ) that bind to pocket 2 are shown in green , and the alpha - atom centers are represented as small tan spheres . ftmap is a computational solvent mapping software used to identify high quality interaction space at the protein surface . by virtue of its fragment - docking algorithm we compare the topographical mapping results for the mdm2 interfaces under study with the corresponding ftmap results ( figure s8 ) . in general , the results from the two methods are remarkably consistent . the interaction regions detected by ftmap at the interfaces of mdm2 overlap precisely with alpha - clusters detected by alphaspace , and aside from a few instances , the overlapping interaction regions are described at a similar resolution ( i.e. , one alphaspace alpha - cluster overlaps with one ftmap probe cluster ) . however , we observe that alphaspace provides more comprehensive coverage of the interaction interfaces . several small auxiliary pockets , detected by alphaspace and directly targeted by the inhibitors we have discussed , go undetected in the ftmap results . additionally , for the apo state of mdm2 , ftmap identifies only two of the seven pockets detected by alphaspace . these unidentified pockets generally exhibit lower fragment - targetability , but their detection is critical to achieve a comprehensive and continuous map of the interface . overall , the clear agreement between methods in identifying and localizing high - quality interaction regions is very encouraging given the strength of the ftmap results published in the literature . in order to evaluate the performance of fctm applied to a larger data set , we used alphaspace to map a total of 33 protein surfaces ( 12 ppis , 12 ippis , and 9 apo structures ) taken from the 2p2i database . these ppis exhibit a diverse set of interfacial structures including various helix , sheet , and loop motifs . if multiple ippi complexes were available for the same protein , we selected the complex corresponding to the highest affinity inhibitor . ( see table s1 for the complete list of pdb ids used in the analysis and the supporting information regarding the two systems omitted due to incompatibility . ) alphaspace maps provide comprehensive coverage of ppi / ippi interfaces . on average , 89% and 95% of all interfacial surface area is characterized for ppis and ippis , respectively , by the sets of fragment - centric contact pockets engaged in binding at the interfaces ( table s4 ) . to confirm the enrichment of high - ranking pockets at the ppi / ippi interfaces , we mapped the entire protein surface of each structure ( for the 12 matching ppi / ippi pairs ) into fragment - centric interaction regions and then scored and ranked each pocket among all other pockets in that protein . we evaluated the rankings for the subset of pockets found at the ppi / ippi interfaces . as shown in figure 8a , high - ranking pockets ( 90th percentile and above ) are sharply enriched at the interfaces of the ppis and the ippis , appearing 2.6 and 4.9 times their expected values . the higher enrichment and lower pocket count at ippi interfaces indicate that ppi inhibitors do target high - scoring alphaspace pockets . ( a ) histograms illustrating the distributions for the percentile rankings of all interface pockets for 12 ppis ( gray ) and 12 ippis ( yellow ) ; ranking is based on pocket scores . dashed gray and yellow lines represent the statistically expected , uniform distributions for ppis and ippis , respectively . ( b ) histograms illustrating the distributions for the percent occupations of all high - ranking ( 90th percentile or above ) ppi ( gray ) and ippi ( yellow ) interface pockets . percent occupation is calculated as the portion of a pocket s alpha - space that is associated with alpha spheres in contact with peptide or inhibitor atoms . we also evaluated the complementarity between high - ranking ppi / ippi pockets and the peptide or inhibitor fragments they bind . pocket - fragment complementarity is expressed as the percent occupation of a pocket , calculated as described in the methods section . figure 8b illustrates that , generally , high - ranking ppi and ippi interface pockets bind to their respective fragments with moderate to high complementarity . however , there is a distinct shift for high - ranking ippi pockets toward higher pocket occupation ; 47% of high - ranking ippi pockets are occupied above 90% compared to 20% of high - ranking ppi pockets . better complementarity may contribute to the generally high ligand efficiency ( le ) documented for successful ippis . furthermore , from an inhibitor design perspective , partially unoccupied ppi pockets represent opportunities to optimize affinity over the native interactions . to leverage the observed enrichment of high - scoring pockets at ippis , alphaspace uses pocket communities , as described in the methods section , to search the protein surface for overlapping clusters of high - scoring pockets . this method is intended to detect fragment - based drug - targetable surface regions from the surface structure alone . to validate the application , we evaluated the performance of pocket communities to identify the known druggable surface regions from the 12 ippis in our 2p2i data set . in 8 out of 12 structures , the ippi interface is identified as the # 1 ranked pocket community ; in 11 out of 12 structures , the ippi interface is identified in the top 3 ranked pocket communities . in 9 out of the 11 identified ippis , the druggable interface is represented by a single pocket community ; otherwise , two pocket communities represent the interface . table 1 shows the high precision in our detection of the druggable interfaces . for 10 out of 11 predicted ippi interfaces , the pocket communities account for 100% of the core and auxiliary pockets in contact with the ligand . and for the 11 identified ippi interface , there are , on average , 2.1 unoccupied pockets included in the corresponding pocket communities . in practice , these unoccupied pockets may represent viable auxiliary pockets yet to be targeted . ( see figure 9 to visualize the druggable pocket communities identified for two example systems : tnfalpha and bcl - xl . ) pocket communities are identified as high - scoring clusters of core and auxiliary pockets and represent potentially druggable surface regions . in the top panels , we visualize all fragment - centric pockets across the surfaces of two example proteins : tnf - alpha ( a ) and bcl - xl ( b ) . each pockets is represented by a single sphere positioned at the centroid of its alpha - cluster ; the spheres are colored by pocket classification : core pockets ( green ) , auxiliary pockets ( blue ) , and minor pockets ( rosy brown ) . the respective fragment - based inhibitors are displayed in red . in the bottom panels , we zoom in to highlight the specific pocket communities identified at the known ippi interfaces . for each core and auxiliary pocket in each community , we now show the detailed alpha - cluster as small spheres ( colored by pocket classification ) , and the alpha - cluster centroids are now shown as transparent larger spheres . the tnf - alpha pocket community ( left ) contains two core pockets , three auxiliary pockets , and community score = 368 . the bcl - xl pocket community ( right ) contains 5 core pockets , 6 auxiliary pockets , and community score = 1208 . to evaluate the overlap between the pocket communities and the set of core and auxiliary contact pockets from each ippi interface , we list the number of interface pockets covered by the communities , the number of interface pockets missed by the communities , and the number of community pockets that fall outside the direct ippi interfaces . we also test the performance of pocket communities to detect drug - targetable communities in the corresponding apo structures near the known ippi interfaces . for 5 out of 9 apo structures , the druggable interface can still be identified as the # 1 ranked pocket community , and 1 more interface is identified by the # 2 ranked pocket community . il-2 , bcl - xl , and zipa no pocket communities are identified at the known ippi interfaces . to clarify , an interface will not register as a pocket community unless at least one core pocket can be detected . however , for the three apo interfaces that do not register as pocket communities , we do observe several fragment - centric pockets scoring very close to the core pocket score cutoff , indicating that the method is sensitive to their latent druggability . we believe that the inability to detect high targetability at these particular interfaces is probably an accurate result for the apo states , especially given a previous report that several apo conformations of targeted ippi interfaces require the rotation of interfacial side chains to improve their targetability . next , we evaluated the performance of pocket matching as a model to track pockets at a fragment - centric resolution between ppi , ippi , and apo structures for the nine systems with available structures for all three states . this allows us to assess the degree of structural conservation or flexibility at the protein surface between the apo structure and the complex structures . for the apo structures , we only include pockets in contact with the inhibitor compound from the corresponding ippi after superimposing the ippi structure onto the apo structure . the motivation here is to explore the ability of alphaspace to identify and assess , specifically , pockets in each apo structure that are near the verified druggable interaction regions from the ippis . ( see figure s9 for a visual representation of the pocket matching results for all nine systems . ) figure 10 presents , as an example , the pocket matching results for menin , which exhibits well - conserved pockets across all three surface states . figure s10 illustrates , for tnfalpha , how the surface structure can change at the fragment - centric resolution from the apo interface to the ippi interface . pocket matching example between the ppi , ippi , and apo protein surfaces of menin . ( left ) each fragment - centric pocket at the respective interface is represented by a colored ring along the pocket score axis : ppi ( left ) , ippi ( center ) , and apo ( right ) . matching pockets are designated by matching ring color . in the surface structures to the right , alpha - clusters and pocket atoms are colored to match their respective ring colors . the green , yellow , and pink pockets are well conserved across all three surface states . the results from table 2 indicate that there are , on average , 4.3 fragment - centric pockets detected near the druggable surface region for each apo structure in the data set , and most of these pockets , 79% , can be matched to binding pockets identified in the ippi structures . comparing the apo vs ippi pocket scores for the set of 31 pockets that match between ippi and apo structures reveals that , while 58% of the fragment - centric pockets do exhibit reduced scores in the apo structures , which reflects the general expectation that pockets are attenuated in apo surfaces , 23% of the apo pockets exhibit higher scores than the matching pockets at the ippi interfaces , and 19% exhibit similar pocket scores between the two states . ( left ) total number of fragment - centric pockets identified at each ppi , ippi , and apo interface . ( right ) matching pocket counts between each possible combination of the three surface states : ppi and ippi , ippi and apo , ppi and apo , or matching across all three states . there are , on average , 11 fragment - centric pockets identified at each ppi interface ( this drops to 8.3 if tnfalpha is omitted which has the largest ppi interface with 33 fragment - centric pockets ) , and roughly half of this pocket count , 5.1 pockets on average , is identified at ippi interfaces . seventy - five percent of all ippi pockets can be matched to pockets identified in the native ppis . interestingly , among these 34 pockets that match between the ppis and ippis , 41% exhibit higher scores in the ippi , 41% exhibit lower scores in the ippi , and 18% exhibit similar pocket scores . this result indicates that many pockets are conserved between these structures but still the interfaces tend to adapt differently to the different binding partners . furthermore , 25% of all ippi pockets are distinct from pockets detected in the ppis , which also highlights the flexibility at functional interfaces and the ability of alphaspace to detect when an inhibitor has targeted a novel pocket . on average , there are 2.6 pockets per system that match between all three protein structure states . in order to highlight the capacity for alpha - clusters to serve as mock molecular binders , we evaluate the volumetric correlation and shape similarity between the bound ppi inhibitors and the corresponding sets of contact alpha - clusters . for the correlation between the total contact alpha - cluster volume and the total ligand volume , we calculate r = 0.77 . this demonstrates a general volumetric correlation , but to evaluate the mock ligand feature more precisely , we can omit from the calculated volumes the specific alpha - atoms representing unoccupied interaction space as well as parts of the inhibitor molecule not in direct contact with the surface ( i.e. , outside 4.5 from the protein surface ) . for this corrected correlation between the occupied alpha - atom volume and the surface - contact ligand volume , , as shown in figure 11 , the linear fit for these corrected volumes is quite similar to the line y = x. this result demonstrates that alpha - clusters roughly approximate the actual size of corresponding molecular ligands . in figure 11 , we show the overlapping alpha - cluster and inhibitor structures for three example systems bcl - xl , il-2 , and xiap in order to illustrate the global shape similarity between the inhibitors and each set of occupied alpha - atoms . ( top left ) the correlation between ligand volume and contact alpha - cluster volume is plotted and evaluated for 12 ippis from the 2p2i database . in blue , we plot the full ligand volume against the volume of the full alpha - cluster after merging the alpha - atoms of all ligand - contact pockets ( r = 0.77 ) . in black , we plot the volume for a reduced set of ligand atoms , excluding ligand atoms not in contact with the protein surface , against the reduced alpha - cluster , excluding alpha - atoms not in contact with the ligand ( r = 0.92 ) . we use three example systems to illustrate the shape similarity between the ligands that bind to each of these systems and the corresponding cluster of contact alpha - atoms from the mapping of each ippi interface : bcl - xl ( orange ) , il-2 ( red ) , and xiap ( yellow ) . alpha - atom centers are shown as small blue spheres , and the shape of each contact alpha - cluster is shown in blue wire representation . the volumes listed are for the reduced ligand and the reduced alpha - cluster . alphaspace represents a departure from existing geometry - based pocket detection in two central aspects . the first is our emphasis on providing a comprehensive map of interaction space across the molecular interface of interest . the map is not limited to hot spots but extends to cover all concave interaction regions engaged in binding and can be systematically expanded further to reveal unoccupied , targetable pockets near the interface . the conventional cavity - centric approach is to screen out what is appraised as insignificant interaction space and deliver only a small set of the highest - ranking pockets . however , as shown for the high - affinity mdm2/p53 ippis , small auxiliary pockets can provide guidance for the extension of fragment - based inhibitors and can provide opportunities to enhance ligand affinity and selectivity . demonstrated for the protein targets in the 2p2i database , alphaspace can effectively match and track pockets between the apo , ppi , and ippi states , detecting pocket conservation as well as pocket modulation between conformations . pocket matching provides a model to study the dynamic integrity of functional interfaces and to characterize interface flexibility at a fragment - centric resolution . the second major divergence of alphaspace is our development of a fragment - centric strategy compared to the long - standing cavity - centric approach . we have found that ppi interfaces are more accurately comprised of arrays of shallow pockets , which exhibit more subtle spatial separation than classical binding sites , but can still contribute to overall binding affinity and are likely to dictate the details of interaction selectivity . the experimental strategies used to target these surfaces are evolving from traditional compound screening approaches to fragment - based screening approaches . this shift has facilitated the successful development of a number of high affinity compounds with unique molecular scaffolds . the fragment - centric design of alphaspace is a direct response to this methodological shift . our strategy is to subdivide broad ppi interfaces into localized fragment - centric interaction regions , reflecting the types of pockets targeted with fbdd . in addition , at this fragment - centric resolution , alphaspace evaluates pocket - fragment complementarity to pinpoint unoccupied interaction space for fragment optimization . accounting for the complete determinants of ppi affinity is a complex challenge ; however , the primary roles of the hydrophobic effect and of vdw interactions have been established and robustly reiterated within the literature . the alphaspace pocket score is not intended to be a definitive , nor absolute , ppi / ippi scoring function . at the least , a more accurate interaction analysis will require the integration of more explicit electrostatic and desolvation terms . rather , our pocket score was developed to be a practical metric reflecting two key structural features related to the hydrophobic effect nonpolar surface area and pocket curvature to discern the approximate , relative targetabilities of fragment - centric interaction regions . importantly , the scoring function is calculated from the surface structure alone , allowing for the screening of any protein surface to search for highly targetable pocket communities as potential starting points for fragment - based inhibitor development . the therapeutic modulation of protein protein interactions represents an important and rapidly expanding field of scientific research . alphaspace fragment - centric topographical mapping ( fctm ) is a new alpha sphere - based pocket detection tool designed to provide a high - resolution visual and quantitative characterization of all interaction space at a ppi interface . we have illustrated how several attractive features of alphaspace can facilitate the rational design and optimization of fragment - based or biomimetic ppi inhibitors . alphaspace is implemented in python , and a copy can be obtained free of charge for academic use from http://www.nyu.edu/projects/yzhang/alphaspace . we hope that alphaspace fctm will become a useful tool for the community to assist in the discovery of novel and potent ppi inhibitors .

inhibition of protein protein interactions ( ppis ) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug - like small molecules . ppis generally feature large and flat binding surfaces as compared to typical drug targets . these features pose a challenge for structural characterization of the surface using geometry - based pocket - detection methods . an attractive mapping strategy that builds on the principles of fragment - based drug discovery ( fbdd)is to detect the fragment - centric modularity at the protein surface and then characterize the large ppi interface as a set of localized , fragment - targetable interaction regions . here , we introduce alphaspace , a computational analysis tool designed for fragment - centric topographical mapping ( fctm ) of ppi interfaces . our approach uses the alpha sphere construct , a geometric feature of a protein s voronoi diagram , to map out concave interaction space at the protein surface . we introduce two new features alpha - atom and alpha - space and the concept of the alpha - atom / alpha - space pair to rank pockets for fragment - targetability and to facilitate the evaluation of pocket / fragment complementarity . the resulting high - resolution interfacial map of targetable pocket space can be used to guide the rational design and optimization of small molecule or biomimetic ppi inhibitors .

a 44-year - old man had bilateral proptosis with gradual onset for 15 months . at that time , a diagnosis of graves orbitopathy was established elsewhere , and moderate improvement was obtained with corticosteroid treatment . 3 weeks prior to our examination , he developed worsening proptosis and bilateral painless swelling of the face and temporal area as well as eyelid edema and chemosis [ fig . 1 ] and was admitted to the hospital . ( a ) initial presentation ( b ) 6 months after corticosteroids treatment his best corrected visual acuity was 20/40 in the right eye ( od ) and 20/25 in the left eye ( os ) . there was a right relative afferent pupillary reflex and mild extraocular movements restriction in all gaze directions general physical examination revealed bilateral palpable but not well - defined , non - fluctuating , firm and immobile mass , involving an area from chin to the zygomatic and pre - auricular region . biochemical profile , serum urea and creatinine levels and thyroid function tests were normal or negative . orbital computed tomography scan revealed enlargement of all extraocular muscles with sparing of tendons , diffuse apical orbital mass in both orbits , temporalis muscle and eyelid edema [ fig . 2 ] . magnetic resonance imaging ( mri ) on t1-weighted images revealed a diffuse thickened subcutaneous hypointense mass , bilateral enlargement of the temporalis muscles and enlargement of all extraocular muscles . the mass was slightly hyperintense on t2-weighted images and showed intense and slightly heterogenous enhancement on post gadolinium injection t1-weighted images [ fig . 3 ] . ( a ) axial ct scan ( b ) coronal ct scan ( a ) mr t1 weighted with contrast ( b ) mr t2 weighted biopsy specimens from the orbital fat , the inferior rectus and the temporal subcutaneous region were performed as well of the cervical limphonodes . the histopathologic finding of the periorbital tissue were replacement of subcutaneous adipose tissue by fibrous stroma containing increased blood vessels , lined by plumped endothelial cells , dense inflammatory infiltrate rich in lymphocytes , eosinophils , plasma cells and several reactive lymphoid follicles [ fig . 4 ] . the lymph node showed follicular hyperplasia with eosinophil precipitate in the germinal center ; in the interfollicular zone , there was an increase of eosinophils among the lymphoid cells and the diagnosis of kd was established [ fig . a reactive lymphoid follicle in the periorbital subcutaneous adipose tissue high - power view of the inflammatory infiltrate rich in eosinophils treatment starting with 80 mg of oral prednisone per day followed by slow tapering led to a significant improvement after 6 months [ fig . 1 ] . after 2 years of treatment when the corticosteroid was discontinued , the patient had mild recurrences of eyelid edema and had to be maintained with low dose oral corticosteroid treatment . his final visual acuity presented slight improvement to 20/30 in od and no change of the 20/25 in os . kimura 's disease is chronic inflammatory disorder of unknown etiology , which presents with tumor - like swellings , mainly in the head and neck region . although infectious etiologies have been postulated , kd is now believed to be related to an autoimmune or a delayed hypersensitivity reaction . an aberrant allergic response is further supported by the association with asthma , allergic rhinitis and conjunctivitis , atopic dermatitis , and peripheral hypereosinophilia as well as raised serum ige levels . it was first described in the chinese literature as eosinophilic hyperplastic lymphogranuloma , but became widely known as kd after kimura et al . reported similar cases . it is usually a localized process without systemic manifestations , but associated conditions have been described including allergic diseases and nephrotic syndrome . it appears to be situated usually in the superior orbit and is largely asymptomatic apart from its mass effect . the condition may mimic specific and non - specific inflammations of the orbit , neoplasias and graves orbitopathy as exemplified in our case . histopathological findings in the orbit or elsewhere in the body are proliferation of lymphoid follicles and germinal centers , showing interfollicular infiltration by eosinophils . computed tomography scan findings are non - specific and consist of homogenously enhancing lymphadenopathy and enlarged salivary glands , with an ill - defined subcutaneous mass extending from the salivary gland . kd usually presents hypointensity on t1-weighted images , but may have different patterns of signal intensity on t2-weighted , depending on the variability of fibrosis and vascularity . the degree of post - contrast enhancement can also be variable and is not related to the degree of hyperintensity on t2-weighted images . the treatment modalities for kd include surgical excision , oral corticosteroid , cytotoxic drugs and radiation therapy . in the present case , an oral corticosteroid greatly reduced the swelling of the eyelids and rectus muscles with mild recurrence after discontinuity of corticosteroid hormone . in conclusion , this paper documents the occurrence of severe bilateral involvement of all recti muscles caused by kd and serves to emphasize the need to include kd in the differential diagnosis of diffuse extraocular muscle enlargement . our case also supports the use of systemic steroids as a valuable treatment modality of such condition .

kimura 's disease ( kd ) is a rare chronic inflammatory disease of unclear etiology , characterized by subcutaneous nodules , mainly in the head and neck region , frequently associated with regional lymphadenopathy . orbital involvement is infrequent and when it occurs , usually affects the eyelid or the lacrimal gland . we report a case of a 44-year - old man that presented with bilateral slowly progressive proptosis that was initially misdiagnosed as graves ophthalmopathy . 15 months of worsening proptosis and the development of facial and temporal swelling led to further investigation . computed tomography and magnetic resonance imaging showed enlargement of all recti muscles and diffuse orbital infiltration . an orbital biopsy was performed and was consistent with the diagnosis of kd . long term oral corticosteroid showed marked improvement of proptosis and facial swelling . this case serves to emphasize that kd should be included in the differential diagnosis of inflammatory diseases of the orbit , even when characterized by predominant involvement of the extraocular muscles .

for several centuries it has been known that a sizeable subset of the stars exhibits a variable energy output ( luminosity ) . the best known and best studied of these variable stars are the cepheids that have a clock - like periodicity . their notoriety comes from the tight relation between their period and luminosity and their consequent role as cosmological distance indicators . in parallel , there exists a class of variable stars with light - curves that instead exhibit various degrees of irregularity . these objects undergo changes in luminosity that can be as large as a factor of forty , indicating violent radial ( i.e. @xmath2 ) pulsations . very little theoretical attention had been devoted to these stars . why do we think that the dynamics underlying these irregular pulsations could be low dimensional and chaotic ? one of the reasons is that decade old numerical hydrodynamical simulations showed low dimensional chaotic behavior and period doubling cascades in models.@xcite however , the observational confirmation of low dimensional chaos in these stars , that is the subject of this paper , had to wait a little longer for a number of reasons . nonlinear techniques are new in variable star astronomy , and it is therefore hard to find data sets that are suitable for a modern nonlinear time series analysis and the search for low dimensional chaos . partially because of the long periods involved , typically tens to hundreds of days , rarely are enough pulsation cycles covered , or they are covered incompletely . generally , professional astronomers have not seen any merit in dedicating the necessary telescope time to what the consider the gathering of useless erratic data . in contrast , thanks to the observations of numerous amateur astronomers , the american association of variable star observers ( aavso ) has recently made available long and relatively well sampled light - curve data of two stars , r scuti and ac herculis . ( in astronomy variable stars were named after the constellation in which they appear preceded by one or two capital letters , until the letters were exhausted ) . both objects are characterized by irregular cycles of @xmath3 75d and 35d , respectively , with alternating shallow and deep minima . the details of the analyses of these light - curves have been published elsewhere.@xcite here we present a summary review . 1 displays typical subsections of the two data sets ( points ) with the solid line showing our smoothed and interpolated fit ( see below ) . these data have been taken visually by many amateur observers worldwide at essentially random times . therefore there is considerable scatter in the data and there are some observational gaps . we have plotted the lightcurves in magnitudes ( for historical reasons defined as @xmath4 luminosity ) rather than the more physical luminosity . for both data sets the error in the magnitudes is found to have a normal distribution , independent of the magnitude ( which is not true for the luminosity itself ) . the reason is to be found in the visual nature of the observations and the logarithmic response of the human eye . we thus work with the magnitude . although the individual observations have a large error associated with them ( 0.20 and 0.15 mag , in r sct and ac her , resp . ) it is possible to extract a reasonably accurate light - curve by averaging and interpolating . the individual errors are larger for r sct , but there are about four times as many data points and the pulsation amplitude is about a factor of 4 larger , so that the error on the final interpolated curve is much smaller for r sct than for ac her . the preparation of the data is a delicate process . we want to eliminate as much observational and other extrinsic noise as possible . however there is additional intrinsic noise associated with turbulence and convection in the star that , strictly speaking , is part of the dynamics . it is well known that well developed turbulent motions constitute high - dimensional behavior , and _ a priori _ it may be objected this would preclude us from uncovering any low dimensional dynamics . the success of our nonlinear analysis provides an _ a posteriori _ indication that the pulsation can be separated into a large amplitude true pulsation , and a low amplitude pulsational jitter . our pre - smoothing eliminates this high - dimensional jitter together with the true noise , leaving a signal that represents the true low dimensional dynamics . to be specific , the bare data were first averaged in 5.0 day bins for r sct and in 2.5 day bins for ac her , followed by a cubic spline smoothing , where the smoothing parameter @xmath5 was a free parameter in the flow reconstruction below . the result is then a lightcurve data set that is sampled at equal time - intervals . figs . 2 and 3 in the top rows show the smoothed and interpolated observational data of r sct and ac her , respectively . in fig . 4 we display the ( normalized ) amplitude fourier spectra of the two observed lightcurves . the fs of r sct has much broader features than the more regular ac her as is to be expected from the appearance of the lightcurves . it is also of interest to look at the broomhead king ( bk ) projections@xcite of a signal . these projections onto the eigenvectors of the correlation matrix are optimal for spreading out the features of the signal . the lowest bk projections for r sct and ac her are thus shown in columns 1 and 5 in fig . 5 . before proceeding with a nonlinear analysis aimed at discovering and describing low dimensional chaos we briefly mention further tests to ascertain that the signals can not be the result of a multi - periodic ( n - torus ) dynamics . for r sct we have performed the following tests.@xcite taking the frequencies of the highest 35 peaks in the fs ( fig . 2 ) we have made a multi - periodic fourier fit for the 35 amplitudes and phases . the fit is quite good over the temporal range of the data set , but when it is _ extrapolated _ in time the signal totally fails to resemble the r sct lightcurve . similarly , a linear autoregressive process with white noise ( ar or arma ) bears little resemblance to the data . both tests indicate that the process that produces the lightcurve is strongly nonlinear.@xcite for ac her , the situation is not so clear - cut because of the high noise level . we note here prewhitening with the frequencies of the 24 highest fs peaks leaves a noise level that is at least 34 times the noise that is expected from the observational error.@xcite there are theoretical reasons for not thinking that so many frequencies could be observed . first these stars are believed to be radial pulsators , and the radial modal spectrum does _ not _ have a structure similar to that of the highest peaks of the fs . further , even if one insisted on nonradial modes , the visual observations are necessarily whole disk observations which can not possibly resolve nonradial modes with @xmath6 . again the required modal spectrum would not be compatible with stellar structure.@xcite the stars can not be evolving ( time - dependent ) multiperiodic systems either . otherwise there should be a correlation between the multitude of smaller peaks in the fourier spectrum when subsequent sections of the data are fourier analyzed , which is not the case . we conclude that neither the r sct nor the ac her lightcurve can reasonably be explained as being periodic or multi - periodic . we now make the assumption that the observed lightcurve @xmath7 has been generated by a low dimensional dynamics in some physical phase - space of _ a priori _ unknown properties , i.e. @xmath8 where @xmath9 is the @xmath10 dimensional state vector of the system . we could equivalently assume a stroboscopic description of the dynamics @xmath11 where @xmath12 . it is natural to assume that @xmath13 is a smooth function of the phase - space variable @xmath14 . a standard reconstruction method starts with the construction of the standard @xmath15dim delay vectors@xcite @xmath16 the _ global _ flow reconstruction method then assumes that there is a single function ( map ) @xmath17 that describes the dynamics all over , @xmath18 embedding theorems@xcite guarantee that for sufficiently large @xmath15 there is a diffeomorphism between the physical phase - space and the reconstruction space ( the latter is then called an embedding space , _ stricto sensu _ ) . following giona _ et al._@xcite and brown@xcite we assume that the function @xmath19 is of a multivariate polynomial form , @xmath20 where the sum runs over all polynomials up to degree @xmath21 . more specifically we use natural polynomials , i.e. polynomials that are constructed to be orthogonal on the data set . however , instead of constructing these polynomials explicitly by recursion and then determining the coefficients @xmath22 @xcite it is equivalent and much faster to expand the function in terms of all monomials up to the same order @xmath21 @xmath23 and then find the expansion coefficients @xmath24 through a least squares minimization of the variance @xmath25 for this purpose a svd ( singular value decomposition ) approach has been found to be most stable and efficient.@xcite the global polynomial reconstruction method was first tested@xcite on the rssler attractor.@xcite using as input a short time - series of only the first one of the 3 rssler variables one obtains a very good estimation of the lyapunov exponents and the fractal dimension of the attractor . furthermore it is possible to determine that this scalar signal was generated by a 3-d flow ( rssler s three first order odes ) , in other words it is possible to determine not only the lowest embedding dimension , but also the dimension of the actual physical phase - space of the dynamics . encouraged by these benchmark results we have applied the reconstruction method to the observational data of stellar lightcurves shown in figs . 2 and 3 . because the observational data sets are so small we have used all the points in constructing the map in eq . we note in passing that in astronomy we are not interested in prediction , but rather in uncovering the properties of the dynamics that underlies the pulsation . in fig . 6 we display the behavior of the error as a function of @xmath15 , which therefore is an in - sample error . the vertically stacked points are for values of @xmath21 ranging from 3 to 6 . this suggests strongly that for r sct the minimum embedding dimension is @xmath26 . for ac her , because of the much larger observational noise , the lowest achievable error level is seen to be much higher . nevertheless fig . 6 can be seen to indicate that we may get away with a minimum @xmath15 of 3 . the behavior of the error norm with dimension by itself is of course insufficient to establish the minimum embedding dimension . it is worthwhile noting that the results obtained with the false nearest neighbor method@xcite are consistent with these respective minimum dimensions of 4 and 3 . how do we decide that a map is good ? for that we have to compare the synthetic signals that a map yields to the original data . ( by synthetic signal we mean data that have been generated by iteration from some seed values with a map generated according to eq . 7 ) . of course , since we have chaotic behavior this comparison has to be done in an average or statistical sense . unfortunately the observational data set is too small to make statistical comparison tests very meaningful . instead we rely on three rather _ ad hoc _ criteria , _ viz . _ ( a ) the signals must have the same appearance , ( b ) their fourier spectra must have the same envelope structure and ( c ) their lowest bk projections should be similar . we have found these simple criteria to be quite useful . for example in our flow reconstructions it is quite clear that any 3d maps for r sct can be rejected for not being able to capture the dynamics of the star ; the synthetic lightcurves , while they may be chaotic , they bear essentially no resemblance to the observational data . in figs . 2 and 3 , bottom rows , we exhibit the synthetic signals we could produce from what we consider the best of these maps for r sct and ac her , respectively . in the bk projections of fig . 6 we display the same two signals , cols . 2 and 7 , respectively . for comparison we also show synthetic signals for r sct that were obtained with a 5d map ( col . 3 ) . 6 shows a 3d reconstruction of ac her . for a comparison of the fourier spectra we refer to the original papers . for further details concerning the sensitivity to the delay @xmath27 , the maximum polynomial order @xmath21 and the data preparation can be found in the original papers.@xcite the reconstructions are seen to be very good and robust for r sct . col . 4 of fig . 6 shows that this remains true when we reconstruct the dynamics with a 4d flow instead of the 4d map of col . 2 . the ac her data are inferior . their signal to noise ratio is much lower and as a result the reconstruction is much less robust . it is nevertheless interesting that we are able to reconstruct a map that can produce synthetic signals with similar properties to the observational data . it is not possible to extract lyapunov exponents and a fractal dimension directly form the observational data because of their short length . however we can obtain these quantities once we have constructed the map or flow . in table 1 we show the lyapunov exponents @xmath28 , ordered from largest to smallest , and of the lyapunov dimension @xmath29 for some of the reconstructions for both r sct and ac her . the latter is defined as @xmath30 where @xmath31 is the largest value such that the sum is positive . the coefficients have been obtained from the maps that have been constructed with the listed parameters @xmath15 , @xmath27 and @xmath21 . ccccccc|ccccccc @xmath32&@xmath27&@xmath21&@xmath33 & @xmath34&@xmath35&@xmath36 & @xmath37&@xmath27&@xmath21&@xmath33 & @xmath34&@xmath35 & @xmath36 4&4&4 & 0.0019 & 0.0016&0.0061&3.05 & 3 & 5 & 6 & 0.0033 & 0.034 & & 2.10 4&5&4 & 0.0017 & 0.0014&0.0054&3.06 & 3 & 10 & 6 & 0.0045 & 0.026 & & 2.17 4&6&4 & 0.0019 & 0.0009&0.0051&3.19 & 3 & 13 & 6 & 0.0069 & 0.030 & & 2.23 4&7&4 & 0.0020 & 0.0011&0.0052&3.18 & 4 & 5 & 5 & 0.0073 & 0.016 & 0.054 & 2.46 4&8&4 & 0.0014 & 0.0010&0.0049&3.07 & 5 & 6 & 4 & 0.0045 & 0.023 & 0.025 & 2.19 5&7&3 & 0.0016 & 0.0005&0.0041&3.27 & 5 & 7 & 4 & 0.0075 & 0.009 & 0.025 & 2.85 6&8&3 & 0.0022 & 0.0003&0.0018&3.52 & 3 & 13 & 6 & 0.0015 & 0.029 & & 2.05 we only note the most important points : ( 1 ) while there is some scatter in the exponents and in the associated fractal dimension @xmath29 , for all successful reconstructions @xmath38 for r sct and 3 for ac her , independently of the embedding dimension . this is an indication that we have achieved an embedding of the dynamics . ( 2 ) the largest of the lyapunov exponents is always positive . this is a confirmation that the signal is indeed chaotic . ( 3 ) we have not shown the second lyapunov exponent because it is always close to zero . this result is reassuring , because it indicates that we are actually close to describing a flow for which one of the exponents would be exactly zero ( autonomous system ) . ( 4 ) for r sct @xmath39 , whereas the inequality is reversed for ac her , indicating a larger dissipation in the dynamics of ac her . as physicists we would like to infer more than just lyapunov exponents and fractal dimensions , because as such they are not very useful . thus it is interesting that from the linearization of the r sct map about its fixed point we found@xcite two spiral roots , one unstable and the second stable with approximately twice the frequency . this led to the interesting physical interpretation that the chaotic dynamics is generated by the nonlinear interaction of two radial modes of pulsation that are in a close resonance condition . such a physical picture is supported by further theoretical considerations.@xcite as for ac her , it is quite likely that two strongly interacting vibrational modes also underlie this dynamics , but that the stronger dissipation alluded to just above compresses the dynamics down to 3d , in the same way the 2d hnon map shrinks to a 1d logistic map for small values of @xmath40 . the flow reconstruction has been applied to real data , _ viz . _ the light - curve of the irregular variable stars r scuti and ac herculis . not only are these data contaminated with a good amount of observational and other extrinsic noise , but we have no a priori information about the dynamics that has generated them . the analysis has shown that the dynamics which generates the light - curve of r scuti has a dimension of four , i.e. the signal can be generated by a flow in 4-d . furthermore the attractor has a fractal dimension @xmath41 3.1 . for the star ac her we find a phase - space dimension of 3 and a fractal dimension @xmath42 . there are no observational data sets available on the even less irregular w vir stars . however , numerical hydrodynamical simulations and their analysis with the global flow reconstruction@xcite indicate also a 3-d phase - space and a fractal dimension of @xmath43 2.01 2.05 . a systematic trend seems to exist , _ viz . _ that as we go from the low luminosity , weakly irregular w vir stars to the high luminosity , strongly irregular rv tau stars , the fractal dimension gradually increases . the fact that these stars have such a low dimensional dynamics must be considered remarkable . they undergo large luminosity fluctuations , up to a factor of 40 for sct , with strong shock waves and ionization fronts criss - crossing the stellar envelope . yet , the overall pulsational behavior is found to be relatively simple . as a result of this nonlinear analysis the nature of the irregular variability of these types of stars is no longer a mystery , but it has been shown to be simply the manifestation of an underlying low dimensional chaotic dynamics . it is a great pleasure to acknowledge the contributions of my collaborators , zoltan kollth and thierry serre . this work has been supported by nsf ( ast9518068 ) .

the light - curves of the two large amplitude variable stars , r scuti and ac herculis , display irregular pulsation cycles with periods of 75 and 35 days , respectively . we review the evidence that the observed time - series are generated by low dimensional chaotic dynamics . in particular , a global flow reconstruction technique indicates that the minimum embedding dimensions are 4 and 3 , for r sct and ac her , respectively , whereas the fractal dimensions are inferred to be @xmath0 and @xmath1 , respectively . it thus appears that the dimensions of the dynamics themselves are also 4 and 3 .

systemic lupus erythematosus ( sle ) is a prototypic autoimmune disease affecting various parts of the body including skin , kidneys , lungs , joints , heart , nervous system , and hematopoietic organs . it is a disease whereby a diverse array of autoantibody production , complement activation , immune complex deposition , and inflammation cause damages in those organs . although the exact aetiology of sle still remains unclear , a combination of genetic risk factors and environmental events is believed to contribute to an irreversible break in immunological self - tolerance . with the introduction of genome - wide association studies , a huge breakthrough has been made in the discovery of sle associated susceptibility genes that in turn advances our understanding of pathogenesis of sle . recently , several reviews have categorised the susceptible genes according to their immunological pathways and cell types . : ( i ) innate immune response including toll - like receptor ( tlr)/interferon ( ifn ) signalling pathways ; ( ii ) adaptive immune response including b , t , and antigen - presenting cells immune signal transduction ; and ( iii ) immune complex clearance mechanism . defects in tlr / ifn signalling pathways cause immune complexes containing self - nucleic acids to interact with tlr7 and tlr9 inside plasmacytoid dendritic cells and b cells endosomes , resulting in the secretion of type i ifn and interleukin ( il)-6 . the combined triggering of both b cell receptors and tlr leads to autoreactive b - cell proliferation . their further differentiation into plasmablasts and autoantibody - secreting plasma cells is induced by type i ifn and il-6 , respectively . tnfaip3 , stat4 , irf5 , trex , and irak1 are the genes involved in upstream and downstream pathways of type i ifn production that have been recently identified . the stat4 gene consists of 24 exons that spread over a 120 kb region on chromosome 2q32.3 . it encodes a transcription factor that mediates signals induced by il-12 , il-23 , and type i ifn and activates the production of ifn- and il-17 . it also directs the differentiation of helper t cells toward the proinflammatory t - helper type 1 and t - helper type 17 lineages that have been shown to play a critical role in the pathogenesis of sle . the stat4 null allele in lupus - prone mouse model confers reduced autoantibody production and glomerulonephritis , indicating that stat4 may be involved in multiple sle - associated phenotypes . there are a few studies involving stat4-deficient lupus - prone mice which demonstrate the role of stat4 in autoantibody production only [ 4 , 5 ] . polymorphisms in the stat4 gene have been found to be strongly associated with sle susceptibility , in particular rs7574865 [ 6 , 7 ] . the simultaneous association of the risk allele t of stat4 rs7574865 with both lower serum ifn- activity and increased ifn--induced gene expression has been reported , confirming that this polymorphism was associated with increased ifn- sensitivity [ 8 , 9 ] . tnfaip3 , or tumour necrosis factor alpha - induced protein 3 gene , encodes the a20 protein which is a negative regulator of the nf-b signalling pathway , an essential pathway in the pathogenesis of sle . a20 is an ubiquitin - editing enzyme required for effective termination of nf-b - mediated proinflammatory responses induced by tlrs , tnf receptor , il-1 receptor , and nod2 . a meta - analysis and imputation study identified a 109 kb risk haplotype spanning tnfaip3 region with lupus nephritis and hematologic manifestation . a nonsynonymous mutation ( c.380 t > g ) , rs223092 , in tnfaip3 gene which causes phenylalanine - to - cysteine change at position 127 of a20 protein has been consistently linked with sle various ethnic groups . the final candidate gene , irf5 , which is ifn regulatory factor 5 , is a transcription factor that mediates inflammatory and immune responses . this factor stimulates the production of the proinflammatory cytokines tnf- , il-12 , and il-6 following tlr signalling as well as transactivation of type i ifn and ifn - induced genes [ 13 , 14 ] . polymorphisms in irf5 cause functional changes in messenger rna , which in turn alter ifr5-mediated transcription resulting in elevated sle risk . it was also suggested that sle patients who carry irf5 risk haplotype and are positive for either anti - rbp or anti - dsdna potentially have higher serum ifn- activity . in this study , we aimed to investigate the association between seven single nucleotide polymorphisms ( snps ) in stat4 , tnfaip3 , irf5 genes , and sle in the south east asian scenario , particularly in the malaysian participants . we also attempted to compare and pool the ors of snps which were significant in the malaysian sle with the other studies through meta - analysis . a total of 790 malaysians were included in this study , which is comprised of 360 sle patients and 430 healthy controls . blood samples were collected from patients diagnosed with sle according to 4 out of acr criteria and healthy volunteers recruited at the university of malaya medical centre ( ummc ) , kuala lumpur , in compliance with requirements as stipulated by the ummc medical ethics committee ( ummc ethics approval code : 733.19 ) . the distribution of samples from malays , chinese , and indians , as well as the ratio of females to males , is shown in table 1 . genomic dna was isolated from the peripheral blood samples by using the standard dna extraction method as described previously . the concentration and purity of the extracted dna were further quantified by measuring the absorbance values at 260 nm and 280 nm via a spectrophotometer . tetraprimer arms - pcr was performed in the genotyping of rs10168266 and rs7601754 in stat4 region , rs2230926 and rs3757173 in tnfaip3 region , and rs4728142 in irf5 region . primers were designed using computer software accessible through the internet at http://cedar.genetics.soton.ac.uk/public_html/primer1.html , developed by ye and team . in silico pcr as described previously was further carried out to ensure the self - designed primers were targeted to the gene regions of interest [ 1921 ] . each pcr reaction was carried out in a total of 10 l , containing 50 ng of template dna , appropriate concentration of inner and outer primers and mgcl2 ( table 3 ) , 200 m dntp , 20 mm tris - hcl ph8.4 , 50 mm kcl , and 0.15 u taq polymerase ( fermentas , vilnius , lithuania . ) . the pcr mixture was then subjected to touchdown pcr , whereby it was incubated for 5 min at 95c , followed by 30 cycles of 45 s denaturation at 95c , 45 s of annealing ( started at temperature 10c higher than annealing temperature , decreasing by 1c per cycle , maintained at annealing temperature for the remaining 20 cycles ) and 45 s of extension at 72c , and a final extension at 72c for 10 min at the end of the cycles . five microlitres of pcr amplicons was electrophoresed on a 2% ( w / v ) agarose gel . the agarose gel was viewed under uv illumination and image was recorded using a gel documentation system . predesigned taqman snp genotyping assays were used to genotype snps where tetraprimers could not be designed for arms - pcr ( probe i d : rs7574865 in stat4 region , c_29882391_10 ; rs729302 in irf5 region , c_2691216_10 ; applied biosystems , ny , usa ) . fifty nanograms of template dna was mixed with 2x taqman gtxpress master mix ( applied biosystems ) and 20x taqman genotyping assay ( applied biosystems ) to make up to a total volume of 10 l . real - time pcr reaction was initiated with pre - pcr read step at 60c for 1 min , followed by dna polymerase activation at 95c for 20 s , 40 cycles of denaturation ( 95c for 3 s ) and annealing / extension ( 60c for 30 s ) , and ended with a final extension step at 60c for 1 min . allele and genotype frequencies were calculated , followed by performing a goodness - of - fit test to evaluate whether or not the observed genotype frequencies of each polymorphisms were departures from hardy - weinberg equilibrium ( hwe ) in control subjects ( p values > 0.05 ) . fisher 's exact test was conducted on 2 2 contingency table using spss software to assess the association of each snp with sle susceptibility in malays , chinese , and indians . p values were adjusted according to bonferroni correction and p < 0.05 was regarded as significant . adjusted ors were computed using logistic regression , whereby major allele and major homozygous genotype of each snp were set as reference group and their ors were adjusted to 1 . the ors of the three ethnicities were combined using mantel - haenszel test to evaluate the overall association of each snp in the malaysian population . the mantel - haenszel ors were calculated using comprehensive meta - analysis version 2.0 software ( biostat , nj , usa ) . random effect model was used when heterogeneity was significant ( p < 0.10 ) ; otherwise , the fixed effect model was used . meta - analysis was conducted using comprehensive meta - analysis version 2.0 software ( biostat ) for the snp(s ) which was / were significantly associated with sle in the malaysian population by including data from other studies as well as the current study . due to insufficient number of indian subjects , we examined the association between stat4 polymorphisms and sle fully and rigorously , with the use of the key words systemic lupus erythematosus , and sle . electronic databases including pubmed , embase , and web of science only fully published articles were included and the eligible studies were identified based on the following criteria : ( a ) the study was original , ( b ) the patients were sporadic cases , ( c ) having available allele and genotype frequency data , and ( d ) having sufficient published data to determine or with 95% ci . data extraction was performed by collecting the following information from each study : the first author 's name , year of publication , ethnicity , the number of cases and controls , and the frequency of minor allele ( maf ) of each polymorphism in both cases and controls . for studies including several independent case - control populations , malay and chinese populations from this study were also included in the meta - analysis . random effect model was used for meta - analysis when heterogeneity was significant ( p < 0.10 ) ; otherwise , fixed effect model was used . by inputting the study name , total number of cases and controls , and maf of cases and controls , comprehensive meta - analysis version 2.0 software calculated the ors , 95% ci , and p values for each study , as well as the pooled or , 95% ci , and p values for the meta - analysis . the goodness - of - fit test demonstrated that all polymorphisms investigated in this study fulfilled hwe in the control group . the malay sle patients were significantly associated with minor alleles of stat4 rs7574865 , rs10168266 , and tnfaip3 rs2230926 , and heterozygous genotype tg of tnfaip3 rs2230926 ( table 4 ) . increased sle susceptibility in chinese population was significantly conferred by minor alleles and minor homozygous genotypes tt of stat4 rs7574865 and rs10168266 . however , after bonferroni adjustment , significant associations were only observed between minor allele t of stat4 rs7574865 and chinese sle patients ( p = 0.028 , or = 1.42 , 95% ci : 1.121.82 ) and between minor allele t of stat4 rs10168266 and malay sle patients ( p = 0.035 , or = 1.80 , 95% ci : 1.202.71 ) . stat4 rs7601754 , tnfaip3 rs3757173 , and irf5 rs4728142 and rs729302 did not show significant association with sle in any of the ethnicities . combined analysis of the three ethnicities was carried out to represent the association of each snp with sle in the malaysian population as a whole . the analysis revealed that only minor allele t of stat4 rs10168266 was significantly associated with the malaysian sle ( p = 0.014 , or = 1.435 , 95% ci : 1.1431.802 ) ( table 5 ) . since stat4 rs10168166 showed significant association with the malaysian sle , meta - analysis was carried out to combine the data from other studies with the current one [ 6 , 2325 ] . four relevant articles were identified eligible and a total of 5 subgroups were included for comparison . data extracted from these articles is shown in table 6 . in the overall analysis , significant association of stat4 rs10168166 with sle the fixed effect model was used as the heterogeneity test did not appear significant ( p > 0.10 ) . the pooled or for the minor allele t was 1.559 , with 95% ci of 1.4591.665 and p value of < 0.001 ( figure 1 ) . understanding the full molecular pathology of sle remains a great challenge , although many insights have been revealed . recognition of self - nucleic acids by toll - like receptors tlr7 and tlr9 on plasmacytoid dendritic cells and b cells is believed to be an important step in the pathogenesis of this disease . increased antinuclear antibodies and production of type i ifn are both correlated with the severity of disease . stat4 , tnfaip3 , and irf5 are genes involved in regulating tlr / ifn signalling pathways . snps investigated in this study have consistently shown associations with sle susceptibility in many populations , especially in asians [ 7 , 24 , 2729 ] . when the various ethnic groups were considered , rs7574865 and rs10168266 of stat4 gene were significant in chinese and malays , respectively . however , only rs10168266 of stat4 was observed to have correlations with sle in the malaysians generally . none of the snps seemed to influence sle in indians . due to population demographics and lower sle risk predisposition , this suggests that the irf5 genetic variants tested for in this study are not linked to sle in our cohort and that there may be other variants that are more important in the indian ethnic group . therefore , it may be concluded from the present study that stat4 gene polymorphisms feature more prominently as the genetic risk factors in the malaysian sle rather than those polymorphisms in tnfaip3 and irf5 . rs10168266 which is located in intron 5 of stat4 gene has been frequently related to sle susceptibility in the asian population , particularly in korean population , and also in the european population [ 6 , 2325 , 30 ] . nevertheless , not many studies were done on this snp and thus only four studies were included in the meta - analysis of this study . after the analysis , the pooled or and p value once again showed that this snp was overall an important risk factor for sle and more attention should be taken . rs7574865 , which was significantly associated with sle in chinese in this study , is located in the third intron of the stat4 gene . the minor / risk allele t has reported associations with other immune - mediated diseases such as rheumatoid arthritis , primary sjgren 's syndrome , type-1 diabetes , crohn 's disease , and ulcerative colitis [ 3134 ] . the association of this particular snp with sle susceptibility was observed in many populations , including both european and asian populations . snp haplotype in the third intron of stat4 marked by rs7574865 was found to be associated with sle susceptibility and it could be responsible for splice variation or regulatory effects of stat4 [ 31 , 35 ] . this coding snp is a nonsynonymous variant causing a phenylalanine - to - cysteine change at residue 127 of the a20 protein . it has been already proven that minor cys127 is relatively stable compared to the phe127 protein , causing it to be less effective at inhibiting tnf - induced nf-b activity . interestingly , as opposed to other findings suggesting that minor allele g was the risk factor of sle , the results of this study demonstrated that it conferred protection against sle in our cohort [ 11 , 24 , 27 , 3640 ] . this study speculates that apart from rs223093 , other factors such as adjacent snps may possibly alter the structure of a20 protein . we suggest that multiple ( at least four ) genes may collectively play critical roles in the development of this disease [ 4143 ] . finally , both snps in irf5 gene investigated in our study were not significant in the malaysian patients although both are fairly established sle risk factors for europeans and some asians [ 4447 ] . the present study was relatively small in contrast to larger studies of sle by other researchers . nevertheless , we present evidence to suggest that the genes involved in tlr / ifn signalling pathways , especially stat4 rs10168266 polymorphisms , contribute to the development of sle in malays and chinese .

polymorphisms in genes involved in toll - like receptor / interferon signalling pathways have been reported previously to be associated with sle in many populations . this study aimed to investigate the role of seven single nucleotide polymorphisms within tnfaip3 , stat4 , and irf5 , which are involved in upstream and downstream pathways of type i interferon production , in sle in the south east asian populations . genotyping of 360 malaysian sle patients and 430 normal healthy individuals revealed that minor alleles of stat4 rs7574865 and rs10168266 were associated with elevated risk of sle in the chinese and malay patients , respectively ( p = 0.028 , odds ratio ( or ) = 1.42 ; p = 0.035 , or = 1.80 , respectively ) . polymorphisms in tnfaip3 and irf5 did not show significant associations with sle in any of the ethnicities . combined analysis of the malays , chinese , and indians for each snp indicated that stat4 rs10168266 was significantly associated with the malaysian sle as a whole ( p = 0.014 ; or = 1.435 ) . the meta - analysis of stat4 rs10168266 , which combined the data of other studies and this study , further confirmed its importance as the risk factor for sle by having pooled or of 1.559 and p value of < 0.001 .

highlights we mapped all known mature cho mirnas to two cho - k1 reference genomes . 212 unique genomic mirna loci and the respective precursor mirna sequences were identified . the genomic loci of 4 polycistronic mirna cluster were confirmed by pcr . the identified sequences were analyzed for snps and conservation compared to mouse . sequence data have been prepared for submission to mirbase mirna sequence repository .

SECTION 1. SHORT TITLE. This Act may be cited as the ``Streamlining Permitting to Enable Efficient Deployment of Broadband Infrastructure Act of 2018''. SEC. 2. EXEMPTION FROM REVIEW FOR CERTAIN COMMUNICATIONS FACILITIES. Title I of the Communications Act of 1934 (47 U.S.C. 151 et seq.) is amended by adding at the end the following: ``SEC. 13. EXEMPTION FROM REVIEW FOR CERTAIN COMMUNICATIONS FACILITIES. ``(a) For Permitting by Commission.-- ``(1) In general.--Notwithstanding any provision of the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) or division A of subtitle III of title 54, United States Code, the Commission shall not be required to perform, and may not require any entity regulated by the Commission to perform, any review under such Act or division as a condition of permitting the placement and installation of a communications facility if-- ``(A) the new facility-- ``(i) will be located within a public right-of-way; and ``(ii) is not more than 50 feet tall or 10 feet higher than any existing structure in the public right-of-way, whichever is higher; ``(B) the new facility is-- ``(i) a replacement for an existing communications facility; and ``(ii) the same as, or substantially similar to (as such term is defined by the Commission), the communications facility that the new communications facility is replacing; ``(C) the new facility is a type of communications facility that-- ``(i) is described in subsection (c)(2)(B); and ``(ii) meets the size limitation of a small antenna established by the Commission; or ``(D) the placement and installation involve the expansion of the site of an existing facility not more than 30 feet in any direction. ``(2) Savings clause.--Nothing in this subsection shall be construed to affect-- ``(A) the obligation of the Commission to evaluate radiofrequency exposure under the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.); ``(B) except as explicitly provided in this subsection, the obligation of any provider of a communications service to comply with the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) or division A of subtitle III of title 54, United States Code; ``(C) the authority of a State or local government to apply and enforce the zoning and other land use regulations of the State or local government to the extent consistent with this subsection and sections 253, 332(c)(7), and 621; or ``(D) the authority or obligations established under section 20156(e) of title 49, United States Code. ``(b) For Grant of Easement on Federal Property.--No review shall be required under the National Environmental Policy Act of 1969 (42 U.S.C. 4321 et seq.) or division A of subtitle III of title 54, United States Code, as a condition of granting a covered easement for a communications facility if a covered easement has been granted for another communications facility or a utility facility with respect to the same building or other property owned by the Federal Government. ``(c) Definitions.--In this section: ``(1) Antenna.--The term `antenna' means communications equipment that transmits or receives electromagnetic radio frequency signals used in the provision of wireless services. ``(2) Communications facility.--The term `communications facility' includes-- ``(A) any infrastructure, including any transmitting device, tower, or support structure, and any equipment, switches, wiring, cabling, power sources, shelters, or cabinets, associated with the licensed or permitted unlicensed wireless or wireline transmission of writings, signs, signals, data, images, pictures, and sounds of all kinds; and ``(B) any antenna or apparatus-- ``(i) that is designed for the purpose of emitting or receiving radio frequency; ``(ii) that-- ``(I) is designed to be operated, or is operating, from a fixed location pursuant to authorization by the Commission; or ``(II) is using duly authorized devices that do not require individual licenses; and ``(iii) that is added to a tower, building, support pole, or other structure. ``(3) Covered easement.--The term `covered easement' means an easement, right-of-way, or lease to, in, over, or on a building or other property owned by the Federal Government, excluding tribal land held in trust by the Federal Government (unless the tribal government of such land requests that the Commission not exclude the land for purposes of this definition), for the right to install, construct, modify, or maintain a communications facility. ``(4) Public right-of-way.--The term `public right-of- way'-- ``(A) means-- ``(i) the area on, below, or above a public roadway, highway, street, sidewalk, alley, or similar property; and ``(ii) any land immediately adjacent to and contiguous with property described in clause (i) that is within the right-of-way grant; and ``(B) does not include a portion of the Interstate System (as such term is defined in section 101(a) of title 23, United States Code). ``(5) Support pole.--The term `support pole' means an upright pole or structure used or capable of being used to support a wireless service facility. ``(6) Utility facility.--The term `utility facility' means any privately, publicly, or cooperatively owned line, facility, or system for producing, transmitting, or distributing power, electricity, light, heat, gas, oil, crude products, water, steam, waste, storm water not connected with highway drainage, or any other similar commodity, including any fire or police signal system or street lighting system, that directly or indirectly serves the public. ``(7) Wireless service.--The term `wireless service' means the transmission by radio communication of voice, video, or data communications services, including Internet Protocol or any successor protocol-enabled services, or any combination of those services, whether provided on a licensed or permitted unlicensed basis. ``(8) Wireless service facility.--The term `wireless service facility' means a facility for the provision of wireless service.''.

Streamlining Permitting to Enable Efficient Deployment of Broadband Infrastructure Act of 2018 This bill amends the Communications Act of 1934 to exempt&nbsp;certain broadband infrastructure project actions, including&nbsp;granting a covered easement, placement and installation of a communications facility, and replacement of a communications facility located in an existing public right-of-way,&nbsp;from environmental review requirements under the National Environmental Policy Act of 1969.