Accel does not appear to like the news in the paper.
I ended up ordering 1,000 of each bookmark because I ran out (My goodness!), and as I was packaging orders earlier today I accidentally knocked the boxes off the guest bed and now there are bookmarks all over the floor. All appear undamaged, but it really is quite the sight! A floor made of Amya bookmarks. I should take a picture!
Anyhow, I hope everyone has a lovely week, enjoy the update!
1st comment. Yay. Accel just started WWIII. By talking to a chick. Pickup fail.
When he gets to the apothecary I hope he rings the bell.
Accel's reaction really is the best way he could have taken the news that everything he'd done in the last 24 hours has been turned into international news stories and is what will be sparking a war in the near future. He looks like he took a punch in the gut.
Wow, I wish I could sell out 1000 bookmarks.
@kuroi_hitsuji: I totally agree with you 100%!!!!!!! That is just so freaking funny!!!!!!!!!!!!!!!!!!!
He handled that better than I expected. Almost smoothly even.
I can almost see the anime triple darkblue lines on his head.
Sounds like things are going well for Amya Chronicles.
wow accel, you didn't say something stupid or screw anything up!


text:
DrErikaRosivatz
Faculty of Natural Sciences, Department of Chemistry
Departmental Operations Manager
+44 (0)20 7594 5718e.rosivatz Website
G02Molecular Sciences Research HubWhite City Campus
Scholarly edition
Thesis dissertation
Filter from 201620152014201320122011201020092008200720062005200420032002 to Filter to 201620152014201320122011201020092008200720062005200420032002
Kugathas S, Audouze K, Ermler S, Orton F, Rosivatz E, Scholze M, Kortenkamp Aet al., 2016, Effects of Common Pesticides on Prostaglandin D2 (PGD2) Inhibition in SC5 Mouse Sertoli Cells, Evidence of Binding at the COX-2 Active Site, and Implications for Endocrine Disruption, ENVIRONMENTAL HEALTH PERSPECTIVES, Vol: 124, Pages: 452-459, ISSN: 0091-6765
Orton F, Ermler S, Kugathas S, Rosivatz E, Scholze M, Kortenkamp Aet al., 2013, Mixture effects at very low doses with combinations of anti-androgenic pesticides, antioxidants, industrial pollutant and chemicals used in personal care products, Toxicol.Appl.Pharmacol.
Many xenobiotics have been identified as in vitro androgen receptor (AR) antagonists, but information about their ability to produce combined effects at low concentrations is missing. Such data can reveal whether joint effects at the receptor are induced at low levels and may support the prioritisation of in vivo evaluations and provide orientations for the grouping of anti-androgens in cumulative risk assessment. Combinations of 30 AR antagonists from a wide range of sources and exposure routes (pesticides, antioxidants, parabens, UV-filters, synthetic musks, bisphenol-A, benzo(a)pyrene, perfluorooctane sulfonate and pentabromodiphenyl ether) were tested using a reporter gene assay (MDA-kb2). Chemicals were combined at three mixture ratios, equivalent to single components' effect concentrations that inhibit the action of dihydrotesterone by 1%, 10% or 20%. Concentration addition (CA) and independent action were used to calculate additivity expectations. We observed complete suppression of dihydrotestosterone effects when chemicals were combined at individual concentrations eliciting 1%, 10% or 20% AR antagonistic effect. Due to the large number of mixture components, the combined AR antagonistic effects occurred at very low concentrations of individual mixture components. CA slightly underestimated the combined effects at all mixture ratios. In conclusion, large numbers of AR antagonists from a wide variety of sources and exposure routes have the ability of acting together at the receptor to produce joint effects at very low concentrations. Significant mixture effects are observed when chemicals are combined at concentrations that individually do not induce observable AR antagonistic effects. Cumulative risk assessment for AR antagonists should apply grouping criteria based on effects where data are available, rather than on criteria of chemical similarity
Orton F, Rosivatz E, Scholze M, Kortenkamp Aet al., 2012, Competitive androgen receptor antagonism as a factor determining the predictability of cumulative antiandrogenic effects of widely used pesticides, Environ.Health Perspect., Vol: 120, Pages: 1578-1584
BACKGROUND: Many pesticides in current use have recently been revealed as in vitro androgen receptor (AR) antagonists, but information about their combined effects is lacking. OBJECTIVE: We investigated the combined effects and the competitive AR antagonism of pesticide mixtures. METHODS: We used the MDA-kb2 assay to test a combination of eight AR antagonists that did not also possess AR agonist properties ("pure" antagonists; 8 mix: fludioxonil, fenhexamid, ortho-phenylphenol, imazalil, tebuconazole, dimethomorph, methiocarb, pirimiphos-methyl), a combination of five AR antagonists that also showed agonist activity (5 mix: cyprodinil, pyrimethanil, vinclozolin, chlorpropham, linuron), and all pesticides combined (13 mix). We used concentration addition (CA) and independent action (IA) to formulate additivity expectations, and Schild plot analyses to investigate competitive AR antagonism. RESULTS: A good agreement between the effects of the mixture of eight "pure" AR antagonists and the responses predicted by CA was observed. Schild plot analysis revealed that the 8 mix acted by competitive AR antagonism. However, the observed responses of the 5 mix and the 13 mix fell within the "prediction window" boundaries defined by the predicted regression curves of CA and IA. Schild plot analysis with these mixtures yielded anomalous responses incompatible with competitive receptor antagonism. CONCLUSIONS: A mixture of widely used pesticides can, in a predictable manner, produce combined AR antagonist effects that exceed the responses elicited by the most potent component alone. Inasmuch as large populations are regularly exposed to mixtures of antiandrogenic pesticides, our results underline the need for considering combination effects for these substances in regulatory practice
Kortenkamp A, Martin O, Evans R, Orton F, McKinlay R, Rosivatz E, Faust Met al., 2012, Response to A critique of the European Commission Document, "State of the Art Assessment of Endocrine Disrupters" by Rhomberg and colleagues--letter to the editor, Crit Rev.Toxicol., Vol: 42, Pages: 787-789
Orton F, Rosivatz E, Scholze M, Kortenkamp Aet al., 2011, Widely used pesticides with previously unknown endocrine activity revealed as in vitro antiandrogens, Environ.Health Perspect., Vol: 119, Pages: 794-800
BACKGROUND: Evidence suggests that there is widespread decline in male reproductive health and that antiandrogenic pollutants may play a significant role. There is also a clear disparity between pesticide exposure and data on endocrine disruption, with most of the published literature focused on pesticides that are no longer registered for use in developed countries. OBJECTIVE: We used estimated human exposure data to select pesticides to test for antiandrogenic activity, focusing on highest use pesticides. METHODS: We used European databases to select 134 candidate pesticides based on highest exposure, followed by a filtering step according to known or predicted receptor-mediated antiandrogenic potency, based on a previously published quantitative structure-activity relationship (QSAR) model. In total, 37 pesticides were tested for in vitro androgen receptor (AR) antagonism. Of these, 14 were previously reported to be AR antagonists ("active"), 4 were predicted AR antagonists using the QSAR, 6 were predicted to not be AR antagonists ("inactive"), and 13 had unknown activity, which were "out of domain" and therefore could not be classified with the QSAR ("unknown"). RESULTS: All 14 pesticides with previous evidence of AR antagonism were confirmed as antiandrogenic in our assay, and 9 previously untested pesticides were identified as antiandrogenic (dimethomorph, fenhexamid, quinoxyfen, cyprodinil, lambda-cyhalothrin, pyrimethanil, fludioxonil, azinphos-methyl, pirimiphos-methyl). In addition, we classified 7 compounds as androgenic. CONCLUSIONS: Due to estimated antiandrogenic potency, current use, estimated exposure, and lack of previous data, we strongly recommend that dimethomorph, fludioxonil, fenhexamid, imazalil, ortho-phenylphenol, and pirimiphos-methyl be tested for antiandrogenic effects in vivo. The lack of human biomonitoring data for environmentally relevant pesticides presents a barrier to current risk assessment
Rosivatz E, Woscholski R, 2011, Removal or masking of phosphatidylinositol(4,5)bisphosphate from the outer mitochondrial membrane causes mitochondrial fragmentation, Cell Signal., Vol: 23, Pages: 478-486
Mitochondria are central players in programmed cell death and autophagy. While phosphoinositides are well established regulators of membrane traffic, cellular signalling and the destiny of certain organelles, their presence and role for mitochondria remain elusive. In this study we show that removal of PtdIns(4,5)P(2) by phosphatases or masking the lipid with PH domains leads to fission of mitochondria and increased autophagy. Induction of general autophagy by amino acid starvation also coincides with the loss of mitochondrial PtdIns(4,5)P(2), suggesting an important role for this lipid in the processes that govern mitophagy. Our findings reveal that PKCalpha can rescue the removal or masking of PtdIns(4,5)P(2), indicating that the inositol lipid is upstream of PKC
Alimonti A, Nardella C, Chen Z, Clohessy JG, Carracedo A, Trotman LC, Cheng K, Varmeh S, Kozma SC, Thomas G, Rosivatz E, Woscholski R, Cognetti F, Scher HI, Pandolfi PPet al., 2010, A novel type of cellular senescence that can be enhanced in mouse models and human tumor xenografts to suppress prostate tumorigenesis, J.Clin.Invest, Vol: 120, Pages: 681-693
Irreversible cell growth arrest, a process termed cellular senescence, is emerging as an intrinsic tumor suppressive mechanism. Oncogene-induced senescence is thought to be invariably preceded by hyperproliferation, aberrant replication, and activation of a DNA damage checkpoint response (DDR), rendering therapeutic enhancement of this process unsuitable for cancer treatment. We previously demonstrated in a mouse model of prostate cancer that inactivation of the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (Pten) elicits a senescence response that opposes tumorigenesis. Here, we show that Pten-loss-induced cellular senescence (PICS) represents a senescence response that is distinct from oncogene-induced senescence and can be targeted for cancer therapy. Using mouse embryonic fibroblasts, we determined that PICS occurs rapidly after Pten inactivation, in the absence of cellular proliferation and DDR. Further, we found that PICS is associated with enhanced p53 translation. Consistent with these data, we showed that in mice p53-stabilizing drugs potentiated PICS and its tumor suppressive potential. Importantly, we demonstrated that pharmacological inhibition of PTEN drives senescence and inhibits tumorigenesis in vivo in a human xenograft model of prostate cancer. Taken together, our data identify a type of cellular senescence that can be triggered in nonproliferating cells in the absence of DNA damage, which we believe will be useful for developing a "pro-senescence" approach for cancer prevention and therapy
Ho KK, Rosivatz E, Gunn RM, Smith ME, Stavropoulou AV, Rosivatz E, Numbere MG, Wong JB, Lafitte VG, Behrendt JM, Myatt SS, Hailes HC, Woscholski R, Lam EWet al., 2009, The novel molecule 2-[5-(2-chloroethyl)-2-acetoxy-benzyl]-4-(2-chloroethyl)-phenyl acetate inhibits phosphoinositide 3-kinase/Akt/mammalian target of rapamycin signalling through JNK activation in cancer cells, FEBS J., Vol: 276, Pages: 4037-4050
Screening a compound library of compound 48/80 analogues, we identified 2-[5-(2-chloroethyl)-2-acetoxy-benzyl]-4-(2-chloroethyl)-phenyl acetate (E1) as a novel inhibitor of the phosphoinositide 3-kinase/Akt pathway. In order to determine the mechanism of action of E1, we analysed the effect of E1 on components of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (mTOR) pathway. E1 demonstrated dose-dependent and time-dependent repression of Akt and mTOR activity in prostate and breast cancer cell lines, PC-3 and MCF-7, respectively. Inhibition of Akt and mTOR activity by E1 also coincided with increased c-Jun NH2-terminal kinase (JNK) phosphorylation. However, the mode of action of E1 is different from that of the mTOR inhibitor rapamycin. Proliferation and cell cycle analysis revealed that E1 induced cell cycle arrest and cell death in PC-3 and MCF-7 cells. Moreover, pretreatment of cancer cells with the JNK inhibitor SP600125 abolished the repression of Akt and mTOR activity by E1, indicating that the inhibition of Akt and mTOR by E1 is mediated through JNK activation. Consistently, E1 repressed Akt and mTOR activity in wild-type and p38-null mouse embryonic fibroblasts (MEFs), but not in MEFs lacking JNK1/2, and JNK-null MEFs were less sensitive to the antiproliferative effects of E1. We further showed that E1 can function cooperatively with suboptimal concentrations of paclitaxel to induce cell death in PC-3 and MCF-7 cells. Taken together, these data suggest that E1 induces cancer cell death through the JNK-dependent repression of Akt and mTOR activity and may provide a valuable compound for further development and research
Garczarczyk D, Toton E, Biedermann V, Rosivatz E, Rechfeld F, Rybczynska M, Hofmann Jet al., 2009, Signal transduction of constitutively active protein kinase C epsilon, Cell Signal., Vol: 21, Pages: 745-752
The protein kinase C (PKC) family is the most prominent target of tumor-promoting phorbol esters. For the PKCepsilon isozyme, different intracellular localizations and oncogenic potential in several but not all experimental systems have been reported. To obtain information about PKCepsilon-signaling, we investigated the effects of constitutively active rat PKCepsilon (PKCepsilonA/E, alanine 159 is replaced by glutamic acid) in HeLa cells in a doxycycline-inducible vector. Upon induction of PKCepsilonA/E expression by doxycycline, the major part of PKCepsilonA/E was localized to the Golgi. This led (i) to phosphorylations of PKCepsilon(S729), Elk-1(S383), PDK1(S241) and Rb(S807/S811), (ii) to elevated expression of receptor of activated C kinase 2 (RACK2) after 12 h, and (iii) increased colony formation in soft agar, increased cell migration and invasion, but not to decreased doubling time. Following induction of PKCepsilonA/E-expression by doxycycline for 24 h and additional short-term treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA), PKCepsilonA/E translocated to the plasma membrane and increased phosphorylation of MARCKS(S152/156). Treatment with doxycycline/TPA or TPA alone increased phosphorylations of Elk-1(S383), PDK1(S241), Rb(S807/S811), PKCdelta(T505), p38MAPK(T180/Y182), MEK1/2(S217/S221) and ERK2(T185/T187). MARCKS was not phosphorylated after treatment with TPA alone, demonstrating that in this system it is phosphorylated only by PKCepsilon localized to the plasma membrane but not by PKCalpha or delta, the other TPA-responsive PKC isozymes in HeLa cells. These results demonstrate that PKCepsilon can induce distinctly different signaling from the Golgi and from the plasma membrane
Rosivatz E, Woscholski R, 2009, Measurement of PTEN activity in vivo by imaging phosphorylated Akt, Methods Mol.Biol., Vol: 462, Pages: 213-222
This chapter describes an indirect approach to measure PTEN's lipid phosphatase activity in vivo. PTEN counteracts phosphatidylinositol 3-kinase action in dephosphorylating 3-phosphorylated phosphoinositides. Therefore, PtdIns(3,4,5)P3-dependent activation and phosphorylation of the survival kinase Akt can be used as readout for cellular PTEN activity. Here we have outlined a detailed procedure employing a phosphoserine-specific anti-Akt antibody to examine the content of phosphorylated Akt by immunofluorescence and its dependence on PTEN activity
Mulet X, Rosivatz E, Ho KK, Gauthe BL, Ces O, Templer RH, Woscholski Ret al., 2009, Spatial localization of PtdInsP2 in phase-separated giant unilamellar vesicles with a fluorescent PLC-delta 1 PH domain, Methods Mol.Biol., Vol: 462, Pages: 135-144
This chapter describes a method for the preparation of giant unilamellar vesicles containing phosphatidylinositol 4,5-bisphosphate that are larger than 20 microm in size. The phospholipids composition of the vesicular membrane is such that fluid lamellar and liquid-ordered or gel phases are formed and separate within the confines of one vesicle. It outlines the preparation of a protein fluorescent label, pleckstrin homology domain from phospholipase C-delta 1, that binds specifically to phosphatidylinositol 4,5-bisphosphate. Using fluorescence microscopy, the presence and spatial position of this phosphorylated phosphatidylinositol lipid on the lipid membrane have been located with the pleckstrin homology domain. We show that phosphatidylinositol 4,5-bisphosphate and the phospholipase C-delta 1 pleckstrin homology domain are located to the fluid phase of the vesicle membrane. This approach can therefore show how membrane physical properties can affect enzyme binding to phosphatidylinositol 4,5-bisphosphate and thus further the understanding of important membrane processes such as endocytosis
Rosivatz E, 2008, Imaging the boundaries-innovative tools for microscopy of living cells and real-time imaging, J.Chem.Biol., Vol: 1, Pages: 3-15
Recently, light microscopy moved back into the spotlight, which is mainly due to the development of revolutionary technologies for imaging real-time events in living cells. It is truly fascinating to see enzymes "at work" and optically acquired images certainly help us to understand biological processes better than any abstract measurements. This review aims to point out elegant examples of recent cell-biological imaging applications that have been developed with a chemical approach. The discussed technologies include nanoscale fluorescence microscopy, imaging of model membranes, automated high-throughput microscopy control and analysis, and fluorescent probes with a special focus on visualizing enzyme activity, free radicals, and protein-protein interaction designed for use in living cells
Busch GK, Tate EW, Gaffney PR, Rosivatz E, Woscholski R, Leatherbarrow RJet al., 2008, Specific N-terminal protein labelling: use of FMDV 3C pro protease and native chemical ligation, Chem.Commun.(Camb.), Pages: 3369-3371
We report an effective strategy for generating N-terminal cysteinyl proteins by proteolytic cleavage using the enzyme 3C pro, suitable for a wide range of applications via native chemical ligation
Ho KK, Anderson AA, Rosivatz E, Lam EW, Woscholski R, Mann DJet al., 2008, Identification of cyclin A2 as the downstream effector of the nuclear phosphatidylinositol 4,5-bisphosphate signaling network, J.Biol.Chem., Vol: 283, Pages: 5477-5485
In addition to the well characterized phosphoinositide second messengers derived from the plasma membrane, increasing evidence supports the existence of a nuclear phosphoinositide signaling network. The aim of this investigation was to dissect the role played by nuclear phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) in cell cycle progression and to determine the cell cycle regulatory component(s) that are involved. A number of cytosolic/nuclear PtdIns(4,5)P2-deficient Swiss 3T3 cell lines were established, and their G 0/G 1/S cell cycle phase transitions induced by defined mitogens were examined. Our results demonstrate that nuclear PtdIns(4,5)P2 down-regulation caused a delay in phorbol ester-induced S phase entry and that this was at least in part channeled through cyclin A2 at the transcriptional level. In summary, these data identify cyclin A2 as a downstream effector of the nuclear PtdIns(4,5)P2 signaling network and highlight the importance of nuclear PtdIns(4,5)P2 in the regulation of mammalian mitogenesis
Rosivatz E, 2007, Inhibiting PTEN., Biochem Soc Trans, Vol: 35, Pages: 257-259, ISSN: 0300-5127
PTEN (phosphatase and tensin homologue deleted on chromosome 10) is well known as a tumour suppressor. In dephosphorylating the 3-position of the inositol ring of phosphoinositides such as PtdIns(3,4,5)P(3), PTEN's lipid phosphatase activity is an important counteracting mechanism in PI3K (phosphoinositide 3-kinase) signalling. This is essential for cell motility and migration due to the achievement of a PtdIns(3,4,5)P(3)/PtdIns(4,5)P(2) gradient that is also involved in metastasis. Furthermore, PTEN's tumour suppressor role is linked to the control of cell-cycle progression and cell proliferation by counteracting Akt (also called protein kinase B) signalling which is PtdIns(3,4,5)P(3)-dependent. Akt is upstream of several kinases involved in proliferation and apoptotic signalling which are often found to be deregulated or mutated in tumours. However, Akt is also the key enzyme in insulin signalling regulating glucose uptake and cell growth. Therefore PTEN has recently moved into the spotlight as a drug target in diabetes. This review summarizes studies undertaken on PTEN's role in glucose uptake, insulin resistance, diabetes and its controversial role in GLUT (glucose transporter)-mediated glucose uptake. Currently available techniques for inhibiting PTEN and the suitability of PTEN as a drug target will be discussed.
Alves CC, Rosivatz E, Schott C, Hollweck R, Becker I, Sarbia M, Carneiro F, Becker K-Fet al., 2007, Slug is overexpressed in gastric carcinomas and may act synergistically with SIP1 and Snail in the down-regulation of E-cadherin., J Pathol, Vol: 211, Pages: 507-515, ISSN: 0022-3417
Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is known to play an important role in tumour progression. The aim of our study was to investigate the mRNA expression of two EMT regulators-Slug and E12/E47-in primary human gastric carcinomas and to compare this with the expression of E-cadherin and other EMT regulators (Snail, Twist, and SIP1). We studied a series of 59 gastric carcinomas by real-time quantitative RT-PCR in formalin-fixed and paraffin-embedded tissues. Thirty-four cases (58%) showed Slug up-regulation in the tumour; reduced or negative expression of E-cadherin was present in 24 of these (71%, p<0.0001). Twenty-one cases (36%) showed E12/E47 up-regulation that was not significantly associated with E-cadherin down-regulation (p=0.5734). Slug up-regulation accompanied by E-cadherin down-regulation correlated with the presence of distant metastases (p=0.0029) and with advanced pTNM stages (p=0.0424). A statistically significant association was found between Slug up-regulation and the expression of SIP1 in intestinal (p=0.0014) and Snail in diffuse (p=0.0067) carcinomas. We present the first study integrating the analysis of several EMT regulators in primary gastric carcinomas and conclude that Slug up-regulation is associated with E-cadherin down-regulation in diffuse and intestinal-type gastric carcinoma, and that this effect could be complemented by the presence of other EMT regulators.
Byrne RD, Rosivatz E, Parsons M, Larijani B, Parker PJ, Ng T, Woscholski Ret al., 2007, Differential activation of the PI 3-kinase effectors AKT/PKB and p70 S6 kinase by compound 48/80 is mediated by PKCalpha, Cell Signal., Vol: 19, Pages: 321-329
The secretagogue compound 48/80 (c48/80) is a well known activator of calcium mediated processes and PKCs, and is a potent inducer of mast cell degranulation. As the latter process is a phosphoinositide 3-kinase (PI 3-kinase) mediated event, we wished to address whether or not c48/80 was an activator of PI 3-kinases. The data presented here reveal that c48/80 is an effective activator of PI 3-kinases as judged by the increased phosphorylation of PKB and p70(S6K) in fibroblasts in a PI 3-kinase dependent fashion. Compound 48/80 effectively translocates PKB to the plasma membrane and induces phosphorylation at serine 473 (S473), detected by fluorescence imaging of fixed cells. At higher concentrations the secretagogue is inhibitory towards PKB phosphorylation on S473. Conversely, p70(S6K) phosphorylation on T389 is unaffected at high doses. We provide evidence that the differential effect on the two PI 3-kinase effectors is due to activation of PKCalpha by c48/80, itself a PI 3-kinase dependent process. We conclude that compound 48/80 is an effective activator of PI 3-kinase dependent pathways, leading to the activation of effectors including PKB/Akt, p70(S6K) and PKCalpha. The latter is only activated by higher doses of c48/80 resulting in an inhibition of the c48/80 induced PKB phosphorylation, thus explaining the observed biphasic activation profile for PKB in response to this secretagogue
Becker K-F, Rosivatz E, Blechschmidt K, Kremmer E, Sarbia M, Höfler Het al., 2007, Analysis of the E-cadherin repressor Snail in primary human cancers., Cells Tissues Organs, Vol: 185, Pages: 204-212
Epithelial-mesenchymal transition (EMT), a normal developmental process, is known to play a crucial role in tumor progression. Molecules involved in this process, such as the E-cadherin repressor Snail, facilitate migration and invasion of carcinoma cells. A growing number of studies addressing the expression of Snail in clinical samples have been reported and are discussed in this review. A total of 2,112 cases from 9 different tumor types were evaluated. So far, a clear picture has emerged only in some cancer types analyzed with regard to overexpression of Snail and clinical-pathological parameters. Currently, it seems that Snail may play a role in hormone-dependent carcinomas but may be of minor importance in gastrointestinal cancers for tumor dedifferentiation and the maintenance of the invasive phenotype. It should be kept in mind, however, that the threshold for Snail activity does not have to be the same in every tumor type analyzed. The recent introduction of well-characterized novel monoclonal antibodies reacting with the short-lived nuclear Snail protein may help to establish a potential clinical usefulness for this master molecule of EMT, at least for certain types of cancer.
Rosivatz E, Matthews JG, McDonald NQ, Mulet X, Ho KK, Lossi N, Schmid AC, Mirabelli M, Pomeranz KM, Erneux C, Lam EW, Vilar R, Woscholski Ret al., 2006, A small molecule inhibitor for phosphatase and tensin homologue deleted on chromosome 10 (PTEN), ACS Chem.Biol., Vol: 1, Pages: 780-790
Phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a phosphoinositide 3-phosphatase, is an important regulator of insulin-dependent signaling. The loss or impairment of PTEN results in an antidiabetic impact, which led to the suggestion that PTEN could be an important target for drugs against type II diabetes. Here we report the design and validation of a small- molecule inhibitor of PTEN. Compared with other cysteine-based phosphatases, PTEN has a much wider active site cleft enabling it to bind the PtdIns(3,4,5)P3 substrate. We have exploited this feature in the design of vanadate scaffolds complexed to a range of different organic ligands, some of which show potent inhibitory activity. A vanadyl complexed to hydroxypicolinic acid was found to be a highly potent and specific inhibitor of PTEN that increases cellular PtdIns(3,4,5)P3 levels, phosphorylation of Akt, and glucose uptake in adipocytes at nanomolar concentrations. The findings presented here demonstrate the applicability of a novel and specific chemical inhibitor against PTEN in research and drug development
Rosivatz E, Becker KF, Kremmer E, Schott C, Blechschmidt K, Hofler H, Sarbia Met al., 2006, Expression and nuclear localization of Snail, an E-cadherin repressor, in adenocarcinomas of the upper gastrointestinal tract, Virchows Arch., Vol: 448, Pages: 277-287
Transcriptional E-cadherin down-regulation can be mediated by Snail, a zinc finger transcription factor. To be able to examine nuclear Snail immunoreactivity in archival human cancers, we established a monoclonal antibody against the purified human Snail protein. The specificity of the selected rat antibody Sn9H2 was demonstrated by Western blot analysis using extracts from different cell lines and by immunofluorescence and immunohistochemistry of primary tissues. Subsequently, a series of 340 adenocarcinomas of the upper gastrointestinal tract, including tumours from the oesophagus (n=154), cardia (n=102) and stomach (n=84), arranged in tissue microarrays, were examined for Snail expression and were correlated to E-cadherin expression and clinico-pathological parameters. Nuclear Snail immunoreactivity was seen in 27 tumours (7.9%) and tended to be more frequent in oesophageal adenocarcinomas (11.1%) than in cardiac (6.9%) or gastric (3.6%) carcinomas (p=0.0428). In 35% of the Snail-positive cases, E-cadherin immunoreactivity was lost. No correlation was found for nuclear Snail expression and tumour grade, Lauren's classification, WHO classification, tumour stage and tumour size. The pattern of Snail expression observed with our new hybridoma, Sn9H2, which is currently the only antibody that reacts with endogenous nuclear (active) Snail, suggests only a minor role of Snail in tumours of the upper gastrointestinal tract
Fuchs M, Hermannstadter C, Specht K, Knyazev P, Ullrich A, Rosivatz E, Busch R, Hutzler P, Hofler H, Luber Bet al., 2005, Effect of tumor-associated mutant E-cadherin variants with defects in exons 8 or 9 on matrix metalloproteinase 3, J.Cell Physiol, Vol: 202, Pages: 805-813
Tumor progression is characterized by loss of cell adhesion and increase of invasion and metastasis. The cell adhesion molecule E-cadherin is frequently down-regulated or mutated in tumors. In addition to down-regulation of cell adhesion, degradation of the extracellular matrix by matrix metalloproteinases is necessary for tumor cell spread. To investigate a possible link between E-cadherin and matrix metalloproteinase 3 (MMP-3), we examined expression of MMP-3 in human MDA-MB-435S cells transfected with wild-type (wt) or three different tumor-associated mutant E-cadherin variants with alterations in exons 8 or 9, originally identified in gastric carcinoma patients. In the presence of wt E-cadherin, the MMP-3 protein level was decreased in cellular lysates and in the supernatant where a secreted form of the protein is detectable. Down-regulation of MMP-3 was not found in MDA-MB-435S transfectants expressing mutant E-cadherin variants which indicates that E-cadherin mutations interfere with the MMP-3 suppressing function of E-cadherin. The mechanism of regulation of MMP-3 by E-cadherin is presently not clear. We have previously found that cell motility is enhanced by expression of the mutant E-cadherin variants used in this study. Here, we found that application of the synthetic inhibitor of MMP-3 NNGH and small interfering RNA (siRNA) directed against MMP-3 reduce mutant E-cadherin-enhanced cell motility. Taken together, our results point to a functional link between MMP-3 and E-cadherin. MMP-3 is differentially regulated by expression of wt or mutant E-cadherin. On the other hand, MMP-3 plays a role in the enhancement of cell motility by mutant E-cadherin. Both observations may be highly relevant for tumor progression since they concern degradation of the extracellular matrix and tumor cell spread
Rosivatz E, Becker I, Bamba M, Schott C, Diebold J, Mayr D, Hofler H, Becker KFet al., 2004, Neoexpression of N-cadherin in E-cadherin positive colon cancers, Int.J.Cancer, Vol: 111, Pages: 711-719
In our study, we aimed to investigate the expression of N-cadherin and E-cadherin and their dependency on epithelial-mesenchymal transition regulators SNAI1, SIP1 and TWIST in human colon cancer. Expression of E-cadherin and N-cadherin was examined by immunohistochemistry in 80 colon carcinomas by using paraffin embedded and formalin fixed tissues. Those cases were partly analyzed for mRNA expression of N-cadherin (42 cases), TWIST (18 cases), SNAI1 (25 cases) and SIP1 (25 cases) by real-time quantitative RT-PCR. Additionally, colon carcinomas that showed amplification of 20q13, the localization of the human SNAI1 gene, were examined. We found cytoplasmic and/or membrane-associated immunoreactivity of N-cadherin in 35/80 (44%) of the cases. However, there was no correlation to upregulated TWIST mRNA levels, as we have shown previously for diffuse-type gastric cancers with abnormal N-cadherin expression. Reduced and/or cytoplasmic E-cadherin immunoreactivity was detected in 19% (15/80) of the cases. Expression of SNAI1 or SIP1 mRNA was not seen in any of the 25 cases analyzed. There was no correlation between amplification of 20q13 and SNAI1 mRNA expression. Remarkably, N-cadherin was almost exclusively expressed in those cases showing normal E-cadherin immunoreactivity, suggesting a mutual exclusion between abnormal E-cadherin reduction and upregulation of N-cadherin. For the first time, we postulate a role for N-cadherin in primary colon cancer progression, which may be similar to the effect discovered by others in breast cancer cell lines, where coexpressed N-cadherin can exert a dominant function over E-cadherin's adhesive function and thus promote tumor invasiveness
Kremer M, Quintanilla-Martinez L, Fuchs M, Gamboa-Dominguez A, Haye S, Kalthoff H, Rosivatz E, Hermannstadter C, Busch R, Hofler H, Luber Bet al., 2003, Influence of tumor-associated E-cadherin mutations on tumorigenicity and metastasis, Carcinogenesis, Vol: 24, Pages: 1879-1886
In this study, we investigated whether tumor-associated E-cadherin mutations impair the tumor-suppressive function of the cell adhesion molecule and influence metastasis formation in a severe combined immunodeficiency mouse model. The investigated E-cadherin mutations were in frame deletions of exons 8 (del 8) or 9 (del 9) and a point mutation in exon 8 (p8). Transfected human MDA-MB-435S carcinoma cells stably expressing wild-type (wt) or mutant E-cadherin were injected into the mouse mammary fat pad. Mice transplanted with wt E-cadherin transfectants developed significantly smaller tumors than animals transplanted with the E-cadherin-negative parental cell line. Animals transplanted with del 9 or p8 E-cadherin transfectants produced medium size tumors, indicating that these mutations impair the tumor-suppressive function of E-cadherin. In contrast, mice transplanted with del 8 E-cadherin transfectants developed tumors of approximately the same sizes as animals transplanted with wt E-cadherin expressing cells. Lung metastases were induced by all cell lines without significant differences. Immunohistochemical analysis of E-cadherin expression in the tumors revealed a heterogeneous staining pattern, indicating loss or down-regulation of E-cadherin in some tumor cells. Metastases were completely negative for E-cadherin. Our data suggest that the type of mutation determines whether the tumor-suppressive function of E-cadherin is impaired
Fricke E, Keller G, Becker I, Rosivatz E, Schott C, Plaschke S, Rudelius M, Hermannstadter C, Busch R, Hofler H, Becker KF, Luber Bet al., 2003, Relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression and Ki-67 staining in diffuse-type gastric carcinoma, Int.J.Cancer, Vol: 104, Pages: 60-65
E-cadherin mutations are found in 50% of diffuse-type gastric carcinoma, but not in intestinal gastric carcinoma. Because cell-cell adhesion mediated by E-cadherin plays an important role in epithelial cell survival, E-cadherin mutations could alter the apoptotic behavior of tumor cells. p53 and Bcl-2 family members are also important regulators of cellular apoptosis. This is the first study that investigates the relationship between E-cadherin gene mutation and p53 gene mutation, p53 accumulation, Bcl-2 expression, and Ki-67 expression in diffuse-type gastric carcinoma (24 cases, E-cadherin mutation status: wild-type in 8 patients and mutant in 16 patients). The mutation status of exons 5-8 of p53 was analyzed by denaturing high pressure liquid chromatography (DHPLC) in formalin-fixed, paraffin-embedded tumor sections, followed by direct sequencing of cases with aberrant chromatographic patterns. p53 mutations were found in 1 of 8 tumors without E-cadherin mutation (12.5%) and in 1 of 16 tumors with E-cadherin mutation (6.3%), a difference that was not statistically significant (p = 1.00). p53 accumulation was found in 8 of 24 tumors (33.3%) by immunohistochemical staining. p53 accumulation was significantly more frequent in tumors without E-cadherin mutations (5 of 8 tumors, 62.5%) than in gastric carcinoma tissues with E-cadherin mutations (3 of 16 tumors, 18.8%, p = 0.03). Bcl-2 staining was not observed in gastric carcinoma cells without E-cadherin mutations, but was detectable in 5 of 16 tumors with E-cadherin mutations (31.3%), a difference that was not statistically significant (p = 0.13). No relationship was observed between Ki-67 staining and the E-cadherin mutation status (p = 1.00). These data suggest that the presence of E-cadherin mutations can significantly alter the accumulation of the apoptosis-regulating p53 protein, whereas no correlation with the p53 mutation status or with Ki-67 staining was observed
Rosivatz E, Becker I, Specht K, Fricke E, Luber B, Busch R, Hofler H, Becker KFet al., 2002, Differential expression of the epithelial-mesenchymal transition regulators snail, SIP1, and twist in gastric cancer, Am.J.Pathol., Vol: 161, Pages: 1881-1891
Epithelial-mesenchymal transition (EMT) involving down-regulation of E-cadherin is thought to play a fundamental role during early steps of invasion and metastasis of carcinoma cells. The aim of our study was to elucidate the role of EMT regulators Snail, SIP1 (both are direct repressors of E-cadherin), and Twist (an activator of N-cadherin during Drosophila embryogenesis), in primary human gastric cancers. Expression of Snail, SIP1, and Twist was analyzed in 48 gastric carcinomas by real-time quantitative RT-PCR in paraffin-embedded and formalin-fixed tissues. The changes of expression levels of these genes in malignant tissues compared to matched non-tumorous tissues were correlated with the expression of E- and N-cadherin. From 28 diffuse-type gastric carcinomas analyzed reduced E-cadherin expression was detected in 11 (39%) cases compared to non-tumorous tissues. Up-regulated Snail could be found in 6 cases with reduced or negative E-cadherin expression. However, there was no correlation to increased SIP1 expression. Interestingly, we could detect abnormal expression of N-cadherin mRNA in 6 cases, which was correlated with Twist overexpression in 4 cases. From 20 intestinal-type gastric cancer samples reduced E-cadherin expression was found in 12 (60%) cases, which was correlated to up-regulation of SIP1, since 10 of these 12 cases showed elevated mRNA levels, whereas Snail, Twist, and N-cadherin were not up-regulated. We present the first study investigating the role of EMT regulators in human gastric cancer and provide evidence that an increase in Snail mRNA expression is associated with down-regulation of E-cadherin in diffuse-type gastric cancer. We detected abnormally positive or increased N-cadherin mRNA levels in the same tumors, probably due to overexpression of Twist. SIP1 overexpression could not be linked to down-regulated E-cadherin in diffuse-type tumors, but was found to be involved in the pathogenesis of intestinal-type gastric carcinoma. We concl
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.
Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00412941&limit=30&person=true

redpajama_set_name: RedPajamaCommonCrawl


text:
Q: Is "a bottle of wine" outdated to refer to alcoholic drink? I asked a friend in UK and got a confirmation the following sentence is an everyday language in UK.

"buy a bottle of wine"

However, searching for the keywords "a bottle of wine" on Amazon gives me this:

just empty wine bottles.
"buy a bottle of wine" seems better, search results includes some wine bottle openers and bottles of wine:

Simply "wine" gives the most weird, which is Women's Slippers!

Is "a bottle of wine" too old-time to get what I want? If yes, what keywords should I use?

A: It is as fine as it has ever been, as this Google Ngram shows:

As your friend and the commenters here say, if I may summarize it, humans are better at interpreting language than computers.

redpajama_set_name: RedPajamaStackExchange


text:
A Day In May: actor Conor Gormally speaks about the play and his hopes for change in marriage equality in Northern Ireland
Emergence Of Colour: Sam McCready exhibition. ArtisAnn Gallery, Belfast, April 3rd, 2019
Apollo Arts youth theatre presents Chicago the musical: interview with actor Sarah Rooney
4th Apr 2019 5th Apr 2019
Tomorrow night, Friday, April 5th, sees Apollo Arts latest release of their take on the classic that is Chicago in Belfast's Crescent Arts Centre.
Apollo Arts is the brain-child of husband and wife team, Pauline Carville and Robin Elliot. Their manifesto is simple and worthy: to produce quality theatre in Northern Ireland, developing young actors while educating and exploring social, cultural and educational themes.
When approached by Crescent Arts and asked to interview one of the cast, my answer was without doubt or a second thought: 'Whoever is playing Roxie'. For those unfamiliar with the show, a brief synopsis goes something like this: two murderers, nightclub star and top-dog in Cook County jail, Velma, runs the show; a mere chorus girl, Roxie, turns up, rocks the boat and things go topsy-turvy.
With brilliant songs and lyrics by composer John kinder and lyricist Fred Ebb, Chicago has stood the test of time. Based on an 1920s play of the same name, the musical has seen a revival since its birth in the 1970s to becoming a staple since regaining its rightful foothold on Broadway and the West End in the mid 1990s.
17-year-old actor, Sarah Rooney chats to CultureCrush NI.
How did you get into musical theatre, do you come from a musical/arts based family?
"My mum always loved the old Hollywood classics. She would always watch musicals and I used to watch them with her, so I'm pretty sure that had an impact on how performing had to do with my future."
I see on your CV you plan to go further with theatre and performing, would musical theatre be the career of your choice?
"Performing has always been on my mind. I would always want to be on stage in front of the camera, or even work behind the camera possibly directing, but it's definitely a career I want to keep at."
I see you been in Mary Poppins, Singing In The Rain and The Farmers' Bash at the SSE Arena, do you ever consider a straight role, as in not musical theatre but straight acting?
"Well, I've always loved doing musicals but I love to be in front of the camera, possibly in a TV show or a movie."
Tell me about the auditions; did you try for different roles, was Roxie your main goal, did Velma or Mama Morton not really appeal to you?
"When I heard that Apollo Arts were auditioning for Chicago I knew I had to do it, it's something I've wanted to do for a long time. When I auditioned I actually intended to go for Velma because of the iconic song Cell Block Tango but I was really happy with Roxie. The story is told through her; it's just amazing to play. It's hard work but she's amazing."
What has working with Apollo Arts done to increase your experience of musical theatre?
"The past six months have been incredible. I've made new friends, I've developed skills and abilities I thought I could never reach. They've gave me methods to follow, like 'Think the thought, feel the feeling and say the line', which has strengthened me, not only as a performer but as a person."
Who is your favourite actor or actress?
"As I said I love the old classic movies so Audrey Hepburn would definitely be my favourite actress. My favourite modern actor would probably be Hugh Jackman or Heath Ledger."
You've played the SSE Arena which holds thousands, did you get nerves before those shows, will you get nerves tomorrow night, and if so what do you do to calm down?
"I definitely get nerves. For the SSE Arena I near died because of the size of the audience. I always take a deep breath before I go on stage. If something happens it can always be fixed, so I know not to worry and just keep going on with it."
What do you plan for after this? You say you 'just keep going for auditions when you see them appear', are you connected to an amateur dramatics group or anything?
"I'm planning to join Apollo Arts because this experience has been incredible and I've loved it. If Apollo Arts wants me back, I'll definitely want to join."
What can the viewer expect during the run? Do you think there's a difference in youth theatre and say maybe more established, professional companies, some from the west End on tour, do you think Apollo Arts and what you, the cast, director etc. are producing is up there?
"Yes, I would definitely say so. They have such a professional background, they keep everything very professional with us, but they also take into consideration that there are young ones as well because Chicago is quite an adult play. This is the high school edition so it is brought down quite a lot {I assume Sarah means some of the scenes have been held back a little due to their racy content} to make it okay for youths."
And there you go. If Sarah Rooney is a barometer of what will be on stage from Friday to Sunday, Belfast is in for a roaring weekend of top notch musical theatre.
Chicago runs from and including Friday, April 5th to Sunday, April 7th. There's a matinee on the Saturday at 3pm. The evening shows start at 8pm. To book your tickets visit http://www.crescentarts.org or phone the box office on 02890 242338
A Day In May: actor Conor Gormally speaks about the play and his hopes for change in marriage equality in Northern Ireland Previous
Emergence Of Colour: Sam McCready exhibition. ArtisAnn Gallery, Belfast, April 3rd, 2019 Next


text:
Taken from

https://github.com/ansible/ansible/issues/31181

outputs are different:

1)

```
ansible-playbook -i issues/datetime/inventory.ini debugging/hostvars_print.yml
```

2)

```
./dump_and_read.sh issues/datetime/inventory.ini
ansible-playbook -i scripts/read_from_out.py debugging/hostvars_print.yml
```

The type is lost in the 2nd, turned into a string. It also prints differently.

redpajama_set_name: RedPajamaGithub


text:
from CLAUDIA LA ROCCO'S PERFORMANCE CLUB....
first published in the Performance Club Blog
"critique as performance"
Letter from Manhattan
Sean Mahoney and Heather McGinley in "House of Joy." Photo: Paul B. Goode.
With Paul Taylor's choreography newly set inside the proscenium arch of the theater that Lincoln Kirstein built for the New York City Ballet, how not to read his work within that context, as well as the overarching Taylorian one from which it springs? You can, for instance, approach his new House of Joy as a gloss on Jerome Robbins's seemingly innocuous Fancy Free (1944). Because what do you see when a sailor saunters on stage in search of female companionship, if not a visual echo?
Intentional, or coincidental, there are clear correspondences. Seeing the Paul Taylor Dance Company at the Koch Theater is like looking at it though a new lens. The theater is larger, but the dances seems more enclosed. These dances have always been self-contained worlds, but here they seem more so. You can peer in. You can fall in, the way Harry Potter falls into Dumbledore's pensieve, that stone basin filled with a silver fog of memories. And, as ever, you can make stuff up about the dances. This is delicious, and fun, to let your mind range around inside a repertory, finding things to think about…. Why take Paul Taylor literally, I wonder? People seem to do it, but while he is plain-spoken and unfancy in movement terms, he is a fanciful dance-maker. Macabre, but fanciful.
Which leads us to the final weekend of the company's three week run, and the Saturday Matinee From Hell. On the program: Oh You Kid (1999), involving among other amusements some larking about by the Ku Klux Klan, and an intermission; House of Joy, that brief work—devoid of pleasure—about some hookers and their pimps and their johns—with one undergoing a beating that looks suggestive of gay bashing, despite the story line; and then after a pause, Big Bertha (1970), a work of such utter depravity that it is a source of amazement to me that it ever got allowed on stage in the first place. This was topped off by Esplanade (1975)—which I adore as who does not?—but I staggered out after Big Bertha to think over what I had just seen. It was so grim that the children in the audience and their chaperones were invited to enjoy an ice cream party during the middle two numbers.
Watching these pieces I wondered, Who are these people rattling around in the choreographer's head? That's for him to know (or not know—his choice) but whether his dance-making is displacement, projection, observation, fantasy, or what have you, once it's on stage it is what it is: art. Dance fiction. What kind, from what period, for whose delectation, and their contemporary applicability and relevance are currently popular questions beyond the scope of the kind of thinking I do about these things. It's becoming trendy to call Taylor dated, or cloaked, though really the only thing dated about him is some of his latter-day costuming. Nothing stales like stretch fabric. In House of Joy, the choreographer is possibly addressing these literalist critiques. He casts his most beauteous female (prima inter pares in a stable of pulchritude) Parisa Kobdeh as a vicious character of indeterminate sex—her breasts are clearly there but she otherwise leans towards male. A biker, in the market for a sado-erotic threesome. She doesn't happen to pick the sad wallflower hooker played by Jeffrey Smith. Like Kobdeh, he's not really successfully transitioned—he has huge biceps—and he can't walk in high heels. His gender is entirely smudged, and the message seems to be: This is make believe, there are characters, this is the theater, my mind is singular but my themes are plural. This isn't about me, and it isn't about you.
Social relevance comes and goes; but these dances are always relevant to me. First of all because they are objects of beauty; and second, because they are interesting. (I like thinking about matters like revealment and concealment.) Further, love is always in season, and true evil never goes out of style.
Amy Young, Michael Trusnovec and Eran Bugge in "Big Bertha." Photo: Paul B. Goode.
Big Bertha is just that. Evil. It seems to show how an unfettered libido functions outside the restraints of common decency and common sense, this season via a true Apollo of the dance theater—Michael Trusnovec, who elsewhere during the run was the sunlit god at the center of Aureole. Trusnovec doesn't look anything like Evil, being a blond prince of lightness, but there he is, got up in clothes from the Eisenhower Administration, and off to the fairground with his wife and daughter. These two are a sub-plot unto themselves: the daughter can dance up a storm whereas the mother is beginning to trip—or always has tripped—over her own feet.
That's an old story. The girl who outshines her mother. Otherwise, this dance is totally Oedipal, except Oedipus here is not enjoying the sexual favors of a woman who unknown to him is his mother—like say, Paul Taylor dancing with Martha Graham in her company, when he was a handsome young man, and she was a ravenous Jocasta, no matter the name of the roles she gave herself. So here's the story Martha's son Paul tells in Big Bertha: At a fair ground, a decorous family happens upon a patriotic looking nickelodeon. (Its name is the same as the infamous German howitzer, but also serves as a portmanteau moniker for things that are large for their type: Big Bertha.) The happy scene immediately spirals out of control, until under the influence of this malign Freudian Jukebox, father debauches and then rapes daughter, to carnival music. Meanwhile, mother discovers dirty dancing, and stripping to her chemise, does some suggestive things with her scarf. And we sit there slack-jawed at what we are looking at. Exquisitely danced, exquisitely lit, exquisitely designed, meticulous in every way. Fantasy is one thing. This is something else. What it seems, and something else.
So let's see. What's going on here? Some people arrive on the scene, just kind of happy-go- lucky normal folks. They torture an authority figure with a wand into playing music and conducting them in dances. The figure takes over, directing them in ways that are shocking and seem to expose their darkest secrets. These are dancers, I thought, and Big Bertha is Terpsichore, the Horrible Awful Muse of Dance.
And then I got it. Bertha is Martha. Because back when he made this dance, Taylor was himself in it. He was telling his own story! He was just an ordinary guy, handsome as the day was long, and he wandered into Martha Graham's studio and the next thing he knew, he was up to his ears in onstage incest. These days, he's moved on. And up. Offstage in his studio, Paul Taylor is up on that platform now.
Paul Taylor is Big Bertha! The dancers wander in, and again and again and again, they start him up, he raises his wand, and out pours choreography. And the next thing they know, they're cross-dressed hookers. They're the stuff of nightmares, of daydreams, of sunshine, of sorrow. Whether Taylor enfolds us in joy or grief or melancholy or horror or sentiment or comedy or introspection or retrospection depends on I don't know what. Maybe the weather. Maybe his dog at any given time. Maybe what arrived in the mail. Maybe what he's reading. Maybe—and this is so likely it goes without saying—the music he decides to work with…
The music. There is one last possibility. What if those people in Big Bertha are attending a matinee? They buy a ticket, the apparatus jerks into action, and people are made to dance. We make them do it. Time and again, year after year. I don't know whether to cry, or to laugh. But this: when Paul Taylor takes a bow—still dreamboat handsome in his dark suit—I rise at once to my feet. He tugs at me. He's a man for all seasons and a man for all moods, and every spring since forever, it's Taylor time.
Bettie de Jong, Eileen Cropley, Paul Taylor and Carolyn Adams in "Big Bertha." Photo: Jack Mitchell.
Thanks to my Performance Club editor Claudia La Rocco. This post first was published on the Performance Club Blog in slightly different format.
©Nancy Dalva 2012
⋅ Labels: Big Bertha, Paul Taylor, Paul Taylor Dance Company, Performance Club


Johnson, Kirsten, Jana Asher, Stephanie Rosborough, Amisha Raja, Rajesh Panjabi, Charles Beadling, and Lynn Lawry. 2008. "Association of Combatant Status and Sexual Violence with Health and Mental Health Outcomes in Postconflict Liberia." JAMA: Journal of the American Medical Association 300 (6): 676–90.
The article reports on the results of research which was conducted in an effort to assess the prevalence and impact of war related psychosocial trauma, including information on participation in the Liberian civil wars, exposure to sexual violence, social functioning and mental health. Researchers surveyed 1,666 adults over a three week period. They found that both female and male former combatants who experienced sexual violence had worse mental health outcomes than noncombatants and other former combatants who did not experience exposure to sexual violence.


There are many more new books out each day by different authors. If your local book store has books of Feng Shui, I suggest you do some browsing and you may most likely find some other books not listed here but are equally good or interesting. I have written a summary of a few Feng Shui authors and their works under this URL:-../books/books.htm If these books are not found in your local book store, you can easily go to any of the good internet book websites e.g. Amazon.com or Barnesandnoble.com and do a search for these authors. You will find more books by them.


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Darren Campbell on Christophe Lemaitre
You are here: Home / Coaching / Darren Campbell on Christophe Lemaitre
August 3, 2010 by Jimson Lee 3 Comments
Last Updated on March 10, 2013 by Jimson Lee
I've received several emails from readers on what I think Christophe Lemaitre. First, I think it's refreshing to see young talent (regardless of the colour of his skin) with amazing potential. Hopefully his parents and management team will keep him level headed, just like Alyson Felix. I am glad to see him still in school, too.
It might be easier for me to critique and add to another coach's comments. In this case, I'll use UK's Darren Campbell comments from Tom Fordyce's article on BBC.
On Overall Thoughts
DC: "You're born with speed, but you're not born a perfect sprinter. Lemaitre, with the raw ability and physical attributes he has, he can improve so much. It might sound strange to say it, but from a technique point of view, there's nothing I look at and think, that's really good."
I could not agree more. Technically, he could improve a lot more, but when you run 9.98 a few weeks after turning 20 years old, who is to argue? Everyone is born with some speed and leg turnover, thus speed CAN be trained. It's losing these fast kids to other sports that is the dilemma today.
On his Drive Phase
DC: "Christophe's drive phase is a work in progress. If you look at Dwain's races, his foot placements over the first 30 metres are always exactly the same. That's why he's so strong in the first part of the race"
"His body position is usually as close to perfect as it can be – perfectly straight, perfectly flat. That gives him maximum strength through his drive phase. If you get your position right and can stay in it, that's the most effective way to run.
"Christophe's is not. He comes upright after about 10-15m, which is far too early. Maurice Greene and Ato Boldon were the ones who changed the thinking with the drive phase – remember how low they used to stay, with their heads down? They changed the way sprinters thought.
I agree his foot placements are all over the place. That's why it's called raw speed. I noted his 100m race at the French Championships on how he ran one race in 41 strides, and another in 43.
See also 2008 Harry Jerome Track Classic - 1500 meters Men
But I think the majority of the coaching world are still living the dogma of the "Maurice Greene drive phase" era. I am referring to stuff like "17 strides in a leaning position, 29 strides upright position" or "40% of your race is leaning and 60% is upright".
Christophe Lemaitre's body mechanics and genetics allows him to run fast despite being upright at the 10 meter mark. We all know the ideal body angles based on hypothetical physics, but every body is made differently.
Know your strengths, know your weaknesses, and execute to the best of your ability.
On Transition Phase
DC: "Lemaitre's transition could be a lot smoother. He pops up to upright suddenly, and although it's only a small thing, when you're talking about hundredths of seconds, it makes a difference.
"It affects your rhythm. If you pop up fast, that's when you feel the wind, and you lose speed, because sprinting is all about momentum and rhythm. When you come up slowly, there's not that sudden feeling of wind resistance in your face. And once you're upright, you're pretty much at top speed. It's very, very hard to change gear once you're upright.
Speaking of "17 strides in a leaning position", if you look at the slo-mo of the video, he actually has his head down and looking down at the track until his 17th step. Just a coincidence, I guess.
I believe your hands have the highest motor skill and control for the human body. So it makes sense to use and control the hands which will control the arms and therefore the entire rhythm for the legs. It's a lot easier to teach someone to use the hand positions as a cue compared to how close your heels should touch your butt.
See also Tyson Gay 100 meter 9.69 Video in Shanghai China
The transition phase is no different. I agree, sprinting is all about momentum and rhythm, and that includes the transition phase. Each phase sets you up for the next phase. At the end of the day, you are simply connecting forty-something strides in a single race.
On Running Style
DC: "His running style at full speed is another area where he will improve. He doesn't rock and roll through his body, but because his foot placements aren't that consistent, he veers. In the first round he went out to the right hand side of the lane. If you stay straight, you'll go quicker.
"It might be that he has more power in one leg. It's almost like a Formula One car – you have to make sure that the power is evenly dispersed.
"I used to practise starting off both legs so one didn't become stronger than the other. I was even careful about my calf muscles, because your left will get stronger than your right just from using the clutch pedal in your car. That's how fine a line you are looking at.
One thing is evident and that he is not running relaxed. Check out the strain on his face or his wrinkles on his forehead for the entire race.
Yes, he foot contacts are all over the place, but that's just a sign of raw speed. He'll only get better with more years of training volumes and of course, more real time racing at the World Class level.
On Arm Position
DC: "Then we come to his arm position and tracking. They're not great – you want to keep an angle of 90 degrees at the elbow, and his arm goes quite straight – but they're not the worst I've seen. They don't go across his body, which is good, because if that happens, your feet strike the ground wider because your arms control what your feet do.
Most world class athletes cannot keep the elbow at 90 degrees on the backswing with the amount of force being generated. It opens up slightly, otherwise the shoulders will tighten, and that will lead to tighter hips and less hip rotation.
See also Armin Hary and the IAAF Reaction Time Rule (Part 1)
Opening up the arms creates a slightly longer pendulum, and thus results in a longer stride. Not a bad thing, as long as you have the leg strength and force to go along with it.
But I disagree with the arms should NOT go across the body. If you watch slo-mo footage of Asafa Powell from the front head-on view, his arms do move across his body. When your body position is fully upright, the arms, or specifically the hands, should be in front of the body near (but not cross) the midline.
On his Build
DC: "Finally there's his build. He doesn't even look like a sprinter – he looks like a 400m runner. So straight away there's muscle he can put on.
"I would focus on bulking up last. You don't want to bulk up with technical problems, because all you're doing is teaching those muscles to run in the wrong way. Get the technique right first."
Standing behind his blocks, his name about to be announced to the crowd. Lemaitre looked unfeasibly fresh-faced, down to the fluffy teenage wannabe-moustache on his top lip. Just how fast could the fully matured man go?"
"I think he's capable of low 9.9s. If he can eradicate these small things, why shouldn't he? Beyond a certain point, sprinting is learnt. It's practising and rehearsing and working on the right things in training. He has all the natural materials he needs."
Since I am biased towards the 400 meters, of course I would love to see him run a 400 meters down the road especially with his 200 meter strength and 100 meter speed. But I'll save that fantasy for another article.
Coaching, Featured Story, Track & Field 100 meters, Ato Boldon, Christophe Lemaitre, Darren Campbell, European Athletics Championships
Anthony Wallace says
DC, I agree that they are doing a great job with him. He is much of a baby to the sport and proper training will show his true potential. 1 thing is true, 70meters in he is flying. I cant wait to see him once he gets the proper training in. For coaches who want to know how to lift properly for speed go get this book "Advanced Techniques in GluteiMaximiStrengtheningII(2)" by Bret Contreras. I have the book that was featured on this website. But this book/pdf really goes into detail about what is really needed to run fast. He even says Charlie Francis was ahead of his peers. I coach @ a Div III school, I have to develop my sprinters and the areas he touch on have change the way i train my athletes, and the way I lift for sprinting.
JMU Track and Field class of 03′
adarian says
I would bet that if he does what is suggested he would run slower and not faster.
Single leg hip thrusts, single leg back extensions and single leg reverse leg press are by far the most functional core lifts for a sprinter out there. Coaches still preaching majority of olympic lifts are out-dated – no offense guys! Bird dog, external hip rotation, swiss ball squeeze, and standing/seated hip abduction + resistance band are also good conditioning lifts.
Bret's lifts are focused on glutes and hamstrings and they're about 2-3x as effective as squats, deadlifts, lunges. However, he fails to include any hip flexor lifts, i imagine any athlete he works with has a poor knee drive.
I know many guys at UK athl;etics do not do these thus i bet many other national coaches don't ebforce these training methods either. These lifts in a periodised program will get record breaking results.
In speed,
http://www.speed-development.co.uk
paul.graham.speed-development@hotmail.co.uk


Collecting and putting in order articles has been my invariable task over years. Probably, this is the task of every person who worked as a stringer or staff writer in a newspaper. Sixteen years of my life I spent in a Belarusian-language weekly newspaper where I was a writer, typesetter, system administrator, and senior-editor. Over those years I wrote several pieces that, not only in my opinion, standed the test of time, thus giving me an impulse to re-publish them in a form (and spirit) of the Internet epoch.
Last updated on 2013-01-30, 18:48. Copyright © 1999-2019 Aleksander Maksymiuk.


Every year, thousands of women and girls are denied their rights and choices by El Salvador's total ban on abortion and its criminalization. Women and girls who are carrying an unwanted pregnancy are confronted with two options: commit a crime by terminating the pregnancy, or continue with the unwanted pregnancy. This report details the pervading cultural and institutional barriers that women and girls in El Salvador face in exercising their human rights, particularly those barriers that obstruct the realization of their sexual and reproductive rights.


text:
A Fortune for Your Disaster
Hanif Abdurraqib
In his much-anticipated follow-up to The Crown Ain't Worth Much, poet, essayist, music critic, and New York Times bestselling author Hanif Abdurraqib has written a book of poems about how one rebuilds oneself after a heartbreak, the kind that renders them a different version of themselves than the one they knew. It's a book about a mother's death, and finally admitting that Michael Jordan pushed off in the '98 finals. It's about forgiveness, and how none of the author's black friends wanted to listen to "Don't Stop Believin'." It's about wrestling with histories, personal and shared, and how black people can write about flowers at a time like this. Abdurraqib writes across different tones and registers, with humor and sadness, and uses touchstones from the world outside—from Marvin Gaye to Nikola Tesla to his neighbor's dogs—to create a mirror, inside of which every angle presents a new possibility.
Tin House Books
Prince: The Last Interview
Prince and Hanif Abdurraqib (Introduction)


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Trap and neutralize: A new way to clean contaminated groundwater
Posted by blexy on April 13, 2016 6:01 pm
Categories: Tech
A team of researchers from Washington University in St. Louis has helped discover a new chemical method to immobilize uranium in contaminated groundwater, which could lead to more precise and successful water remediation efforts at former nuclear sites.
Researchers in the lab of Daniel Giammar, the Walter E. Browne Professor of Environmental Engineering in the School of Engineering & Applied Science, ran a series of experiments in a laboratory setting using water containing uranium — present in contaminated groundwater at various sites in the United States as a legacy of Cold War-era processing and waste disposal activities associated with nuclear materials production.
Calcium and phosphate work together chemically to immobilize uranium, which is shown to lead to increased cancer risk and liver damage in humans when ingested. Past field studies, including one at the Hanford Site in the state of Washington, focused on an in situ solution that injected phosphates directly into contaminated groundwater. Remediation efforts were not fully successful, because the scale of overlap for the calcium, uranium and phosphates was limited.
"A challenge with subsurface remediation is finding the right way to bring the necessary ingredients together in a poorly-mixed system," Giammar said. "In the field-scale test, much of the added phosphate never reached the uranium because it precipitated out near the injection well. The solution is to figure out scenarios where it is possible to send the phosphate to where the uranium is, and other scenarios where the phosphate can be added to a location where the natural groundwater flow will bring the uranium into contact with it."
The research was led by Giammar and Vrajesh S. Mehta, who earned his PhD at the School of Engineering & Applied Science. Other co-authors are Zheming Wang, senior researcher at the Environmental Molecular Science Laboratory in Richland, Wash.; Jeffrey G. Catalano, associate professor of earth and planetary sciences in Arts & Sciences at Washington University; and Fabien Maillot, former postdoctoral researcher in Catalano's lab.
In three different types of experiments conducted in Giammar's lab, the researchers first determined the exact level of calcium in the water. They were then able to add specific amounts of phosphate that formed calcium phosphate, chemically neutralizing and structurally incorporating the uranium. The exact combination of calcium and added phosphate rendered the uranium inert and trapped it in the groundwater.
Giammar's lab will continue this research, with the goal of developing a technique to tailor the location of phosphate injection that would be used in conjunction with the groundwater's existing calcium to remediate the uranium also present.
"The results of this work suggest that there will not be a one-size-fits-all approach to using phosphate to remediate uranium-contaminated groundwater," Giammar said. "With knowledge of the location of the uranium contamination and the composition of the groundwater, we can decide whether to inject phosphate directly into a plume of uranium-contaminated groundwater or to inject phosphate downstream of the uranium to form a calcium phosphate barrier."
The research findings were recently published in the journal Environmental Science & Technology.
The above post is reprinted from materials provided by Washington University in St. Louis. The original item was written by Erika Ebsworth-Goold. Note: Materials may be edited for content and length.


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Elon Musk Claims He Was Forced To Settle With The SEC Over His 'Funding Secured' Tweet
Frank Broholm
Tesla CEO Elon Musk is asking a federal judge to file a consent decree with the Securities and Exchange Commission that requires his tweets to be approved by a lawyer before he can post them.
The decree, which was signed in 2018 after Musk's infamous "funding secured" tweet, is being used "to trample on Mr. Musk's rights to the First Amendment and to curtail his advance speech," his lawyers said in a statement on Tuesday. lawsuit. Musk also wants to block an SEC subpoena related to his tweets about the sale of 10 percent of his stake in Tesla.
Musk sent the infamous tweet on August 7, 2018, in which he claimed to have the financing to take Tesla private for $420 a share. (Tesla has been a publicly traded company since 2010)
"Trampling Mr. Musk's First Amendment Rights"
The SEC immediately launched an investigation, eventually concluding that while he had had a few meetings with Saudi Arabia's state wealth fund, Musk "never discussed a $420 a share private transaction with a potential funding source, did nothing to investigate whether it would be possible for all current investors to stay with Tesla as a private company through a 'special fund', and have not confirmed Tesla's investors' support for a possible private transaction."
But in a new court filing Tuesday, Musk argues that "funding" used to be secured, and there used to be investor support." He said he felt pressure to settle the matter with the SEC or jeopardize Tesla's financial security.
"Despite this, the SEC's relentless regulatory pressure, coupled with the collateral impact of the SEC's complaint against me, created a scenario where I was forced to sign the consent decree in 2018," Musk said. "Tesla was a less mature company and the SEC's action would jeopardize the company's funding."
Musk said he planned to sign the decree until he learned it could negatively affect his other companies — Space X, Neuralink and The Boring Company — as well. He said he tried to get out but finally relented after the SEC charged him with securities fraud and several major Tesla shareholders threatened to sell their stake in the company.
"financing" used to be secured, and there used to be investor support."
"I just wanted to settle for helping Tesla, but I didn't want to harm the other companies," Musk said. "It felt wrong to do that."
The SEC is investigating whether recent stock sales by Musk and his brother Kimbal Musk may violate insider trading rules. The investigation began late last year after Musk and his brother sold $108 million worth of Tesla stock The Wall Street Journal† That sale came the day before Elon Musk polled his Twitter followers whether he should sell 10 percent of his stake in the company — pledging to abide by the poll results.
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In this week's filing, Musk defended his actions as his attorneys try to quash the agency's subpoena. "I have never lied to shareholders," Musk writes. "I would never lie to shareholders. I have entered into the consent decree for the survival of Tesla, in the interest of its shareholders."
Musk's conflict with the SEC has flared up in recent weeks. The billionaire's CEO accused the agency of subjecting him and his company to "endless, baseless investigations." He also alleged that the agency ignored his commitment to pay $40 million in fines to Tesla shareholders, according to the 2018 settlement, and he alleged that the SEC leaked information about federal investigations without providing any specific evidence to back up his claim. rods.
Frank Broholm had acquired considerable experience in writing and editing publications before recruited by The Media Today Chronicle News portal as Editorial Manager. His key task is to conduct effective business reviews based on the most recent business strategies. Due to his stronghold and understanding over finance, marketing, business, and trade-related topics, he is known as a business counselor among the staff & managing the Market News column. His expertise in business-related topics is quite impressive. His business-related concepts are on fingertips, which aids in illustrating the business articles in brief and defined way, clear to even an amateur. He pursued his post-graduation in Finance from a UK-based university.
Amazon cuts more than 18,000 jobs in a second round of...
Diksha - January 19, 2023
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The Gibbs reflective cycle helps the nurse to learn from ongoing practice and to reflect and learn from the experience in order to provide better care in future cases (Lia, 2015).
Gibbs Model of Reflection - Scribd Scribd.com Gibbs (1988) model of reflection Gibbs is another common model of reflection that is used within the health professions. Gibbs is clear and precise allowing for description, analysis and evaluation of the experience helping the reflective practitioner to make sense of experiences and examine their practice.


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5 facts you need to understand the new global order
by Robert Muggah & Yves Tiberghien
At least three competing versions of the future world order crashed together at the World Economic Forum's gathering in Davos last week. There was the one peddled by a combative Donald Trump, calling for a full-scale US retreat from the current order. Another came from Chinese leaders who proposed a new global economic system built around Beijing. Meanwhile, Canada's Justin Trudeau and France's Emmanuel Macron urged western leaders to double down on the current liberal order.
It would be a mistake to dismiss their speeches as empty grandstanding. This debate is deadly serious. The outcomes will likely determine the future of global stability and the security and prosperity of everyone. If the leaders of major countries and international organizations cannot see eye to eye, we are in for a very rough ride. Rather than withdraw, what is needed more than ever are new ideas, institutions and blueprints to navigate the coming storm.
We are living in abnormal times. The global liberal order is in an advanced state of meltdown. And as the world rapidly shifts from a uni-polar to a multi-polar reality, the international system itself is exposed to profound instability. If the situation is not handled with extreme care, the potential for a major collapse is real. The question is whether our world leaders are capable of fully understanding what is happening in real time and can muster the collective action to set new rules of the road.
The old global liberal order served as the bedrock of peace and stability since 1945. It was purposefully designed by the US and its western allies to prevent armed conflict and the economic nationalism that gave rise to it. It is composed of the United Nations, the International Monetary Fund and World Bank, the World Trade Organization, the North Atlantic Treaty Organization, the G20 and a thicket of treaties and agreements. While experiencing its ups and downs, it set the rules for a stable positive-sum game.
While virtually everyone agrees that a rules-based system is essential to managing security and trade, a power struggle is underway over who writes and enforces them. The spectacular rise of China over the past two decades and the relative decline of the US mean that sparks are bound to fly. Yet most westerners are only dimly aware of what's occurring since the rug was so quickly pulled out from under them. The potential for catastrophic miscalculations – including US trade actions against China – are rising, with potentially devastating cascading effects to the global economy.
To get to grips with the seismic shifts taking place, consider these five facts.
1) China is in the process of surpassing the US economically. By one measure, 35% of world growth from 2017 to 2019 will come from China, 18% from the US, 9% from India, and 8% from Europe. By 2050, the top five largest global economies are most likely to be China, India, the US, Brazil and Indonesia. Is the west even remotely prepared for this kind of world?
2) China is leading the largest urbanization and infrastructure development scheme on earth. Already in its fifth year, the $900 billion "One Belt and One Road" (OBOR) project includes new roads, shipping lanes and building projects stretching to over 65 countries. The idea is to literally rewire global trade from China throughout Asia, the Middle East, Africa and Europe. While details are hazy, OBOR is being financed by Chinese state banks, with a modest strategic contribution by a new Chinese-backed Asian Infrastructure Investment Bank in partnership with other institutions.
3) China is set to become a global green powerhouse. China signalled its intention to take the lead on climate change reduction after signing the 2015 Paris climate agreement. By 2025, most new cars in China will be fully electric vehicles. China is aggressively cutting coal usage. Already, over 60% of high speed rail in the world is in China (10 times the length in Japan, for example). China also recently committed to achieving blue skies in all of its major cities within three years. The changes are already being felt: Beijing air is 30% cleaner this winter than last winter.
4) China is also setting the global pace on a digital economy, including cashless payments. In major cities, up to 90% of all commercial and retail transactions in convenience stores and cafes are occurring through Alipay and Wechat. E-commerce delivery in large Chinese cities through Alibaba is the currently the fastest in the world. One company, Alibaba, racked up sales of $25 billion in just one day – dwarfing the returns of so-called Black Friday and Cyber Monday in the US.
5) Chinese universities are also vaulting to the top of the international rankings. Two schools – Peking University and Tsinghua University – leapfrogged from well below the top 200 to the top 30 within five years. There are another 40 universities that are not far behind and are set to enter the elite in the coming years. While Chinese students are still seeking out educations in top schools in North America and western Europe, soon they won't have to.
All the while, the west seems to be asleep at the wheel. There is a certain irony in our current predicament. On the one hand, the world is experiencing unparalleled levels of prosperity and connectivity, due in no small part to the US-backed global liberal order. Yet these advances are associated with ever greater complexity and systemic risks, increasing the liberal order's vulnerability to collapse. The world's global and national institutions are increasingly incapable of managing stresses to the system. Democracies, it turns out, lack the incentive systems to address higher-order and longer-term imperatives.
Faced with threats ranging from climate change to massive technological advancement, the world is in desperate need of stable and able global governance. And yet there is surging opposition to liberal governance due to rising inequalities and frustration with the perceived failures of the liberal order. Francis Fukuyama and Jan-Werner Müller view populism and the rise of parochial economic nationalism as among the gravest threats to future stability. The risk of a disorderly collapse of the system is more real than ever.
If we are to survive the global geopolitical transition, we must first accept that the era of US hegemony is over. Instead, the world is shifting to a new multi-polar order with the US and China at its centre. We need to restore and rebuild stable institutions and rules that acknowledge the changed context. They will need to be more inclusive, representative and legitimate. The role of international mechanisms of cooperation (such as the G20), regional organizations, non-state actors – especially financial and philanthropic actors – will also need to be elevated. What's more, cities are claiming their place – witness Urban20, a collaboration between the world's largest cities, to be formally launched in October 2018.
All of this will be hard to swallow for stalwarts of the global liberal order. It will also need to be explained to a public that is accustomed to linear change. The current transformations are both non-linear and increasingly exponential, processes that are hard for humans to grasp. We are fixated to the forward march of democracies and the underlying principles on which they are based, yet we must learn to compromise and accommodate multiple value systems.
The next order will be more complex and potentially more precarious, but that is the brave new world we face.
Image credit: REUTERS/Damir Sagolj/File Photo


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Home Tips, Tricks & Trends
5 Most Luxurious Cars in the World
by Marci Houghtlen on October 29, 2019
Through the decades, manufacturing cars has become more and more of an art form. The most expensive cars in the world are not only a symbol of status but a testimony to the companies and engineers that built them. Though most of us may not be able to afford the most luxurious and expensive cars in the world, it is free to appreciate these marvels of modern engineering.
Full of luxurious materials, created by top-notch engineers, and designed to make your jaw drop, these cars are some of the most expensive in the world. Although they may be out of your price range, each one of them makes it easy to dream. Ahead are the most luxurious cars in the world.
1. Mercedes-Benz AMG One
For the 50th anniversary of Mercedes-Benz's AMG division, the car brand created a one-of-a-kind luxury vehicle named the AMG One. Its behind-the-driver engine puts out more than 1,000 hp from a 1.6-liter turbocharged V6 that's helped along by four electric motors: two for powering the front wheels, one that powers the rear wheels, and one that helps power the turbocharger.
For a cool $2.5 million, the AMG One is a supercar that can rev up to 11,000 rpm. Meant to have the "heart of a Formula One race car," according to Digital Trends, it has tight driving quarters, a low and aerodynamic shape, a racing-style steering wheel, and multiple different driving and suspension modes.
2. Aston Martin Valkyrie
.@AndyatAston: "Today is a real milestone in not only Aston Martin's history but for our industry as a whole. Aston Martin Valkyrie continues to redefine what you and I recognise as a hypercar."#BritishGP #F1 #AstonMartinValkyrie pic.twitter.com/tkHMD1C0kf
— Aston Martin (@astonmartin) July 13, 2019
According to Motor 1, the Aston Martin Valkyrie has an estimated price tag beginning at $2.6 million. Resulting from a partnership between Aston Martin and the Red Bull Racing Formula One team, the futuristic Valkyrie is a new hybrid hypercar that can reach top speeds of more than 200 miles per hour. Aston Martin said it plans to build 150 of these models, with a limited model coming at a later date. The Valkyrie's 6.5-liter, V12 engine puts out 1,160 hp and 664 lb-ft of torque.
3. Ferrari Pininfarina Sergio
Custom-made for only a handful of pre-existing customers, the spectacular Ferrari Pininfarina Sergio is worth around $3 million. True to Ferrari's supercar fashion, the Pininfarina houses a 562 hp, 4.5-liter V8 engine, on an ultra-light body. Designed for hugging curves, it has a low, aerodynamic body and headrests built directly into the roll cage. The Pininfarina Sergio can reach 60 miles per hour in around 3 seconds. This invite-only supercar was designed to commemorate the 60-years worth of partnership between Ferrari and designer Pininfarina.
4. Lamborghini Veneno
Jumping up in luxury price tags, the Lamborghini Veneno was named for the Italian word for poison. The undeniably cool supercar was created as a celebration of Lamborghini's 50th birthday and is worth an estimated $4.5 million. Incredibly fast, the Veneno can reach 60 miles per hour in 2.9 seconds with a 6.5-liter V12 engine that puts out 740 hp and 507 lb-ft of torque. The Veneno slightly resembles an alien spaceship with headlights that stretch over the hood, an incredibly low body, and the clean, harsh lines of a stealth fighter jet.
5. Bugatti La Voiture Noire
Newly crowned the most expensive car in the world, the Bugatti La Voiture Noire is truly one-of-a-kind. Bugatti only produced one of these models and it's rumored to have a price tag of around $19 million. French for the term "the black car," the La Voiture Noire has a C-line bodyside design, six tailpipes, and an 8.0-liter, quad-turbo W16 engine. According to Road and Track, this luxurious hypercar can put out 1,479 hp and 1180 lb-ft of torque.
Arriving for Bugatti's 110th anniversary, the La Voiture Noire has a handcrafted, carbon fiber body that's meant to only be seen when you want it to be. It has an extended front end, a seamless windshield, and smooth lines from front to end.
Tags: Aston Martin Bugatti Ferrari Lamborghini luxury cars mercedes-benz


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This is a list of Bulgarian football clubs in European competition. Bulgarian clubs have participated since 1956, when CSKA Sofia entered the 1956–57 European Cup.

Achievements

Biggest Achievements

Statistics
As of 3 November 2022.

 Most European Cup / Champions League competitions appeared in: 25 – CSKA Sofia
 Most Inter-Cities Fairs Cup / UEFA Cup / Europa League competitions appeared in: 26 – Levski Sofia
 Most UEFA Europa Conference League competitions appeared in: 2 – CSKA Sofia
 Most Cup Winners' Cup competitions appeared in: 11 – Levski Sofia
 Most Intertoto Cup competitions appeared in: 5 – Spartak Varna
 Most competitions appeared in overall: 58 – CSKA Sofia
 First match played: CSKA Sofia  8–1 Dinamo București (1956–57 European Cup R1)
 Most matches played: 258 – CSKA Sofia
 Most match wins: 100 – CSKA Sofia
 Most match draws: 56 – CSKA Sofia
 Most match losses: 94 – Levski Sofia

 Biggest win (match): 10 goals
 Levski Sofia 12–2 Lahden Reipas (1976–77 European Cup Winners' Cup R1)
 Biggest win (aggregate): 16 goals
 Levski Sofia 19–3 Lahden Reipas (1976–77 European Cup Winners' Cup R1)
 Biggest defeat (match): 8 goals
 Sigma Olomouc 8–0 Velbazhd Kyustendil (2000 UEFA Intertoto Cup R2)
 Biggest defeat (aggregate): 10 goals
 Slavia Sofia 0–10 Partizan (1988–89 UEFA Cup R1)

UEFA coefficient and ranking
For the 2020–21 UEFA competitions, the associations will be allocated places according to their 2019 UEFA country coefficients, which will take into account their performance in European competitions from 2014–15 to 2018–19. In the 2019 rankings that will be used for the 2020–21 European competitions, Bulgaria's coefficient points total is 17.500. After earning a score of 4.000 during the 2018–19 European campaign, Bulgaria is ranked by UEFA as the 28th best association in Europe out of 55.

 26  Azerbaijan 19.000
 27  Israel 18.625
 28  Bulgaria 17.500
 29  Romania 15.950
 30  Slovakia 15.625
 Full list

UEFA country coefficient history
(As of 2 September 2022), Source: Bert Kassies website.

Appearances in UEFA competitions

App. = Appearances; P = Matches played; W = Matches won; D = Matches drawn; L = Matches lost; EC = European Cup; UCL = UEFA Champions League; UC = UEFA Cup; UEL = UEFA Europa League; CWC = UEFA Cup Winners' Cup; UIC = UEFA Intertoto Cup.

Active competitions

European Cup / UEFA Champions League

Notes
 Note 1: A number of Eastern European clubs withdrew from the first two rounds when UEFA paired up all of the Eastern European clubs against one another due to the disastrous situation in Czechoslovakia.
 Note 2: Botev Plovdiv were replaced Levski Sofia as the Sofia's club barred from entering the European competitions after the riots during the Bulgarian Cup final.
 Note 3: The Bulgarian clubs were not entered the Champions League during these seasons as a result of restructuring by UEFA, with entry to the competition limited to the continent's top 24 countries. The league champions entered the UEFA Cup instead.

UEFA Cup / Europa League

UEFA Europa Conference League

Defunct competitions

Cup Winners' Cup

Notes
 Note 1: A number of Eastern European clubs withdrew following UEFA's decision to separate western and Eastern countries due to troubles in Czechoslovakia.
 Note 2: CSKA Sofia were barred from entering the European competitions after the riots during the Bulgarian Cup final.

UEFA Intertoto Cup

Notes
 Note 1: No club was elected by Bulgarian Football Union for the participation in the tournament in that season.

References

External links
UEFA Website
Rec.Sport.Soccer Statistics Foundation

European football clubs in international competitions

redpajama_set_name: RedPajamaWikipedia


In this week's episode: we're looking at entrepreneurship! From entrepreneurship case studies like Juicero, to the history of the world's first (caveman) entrepreneurs, this is one that will improve the lives of absolutely everyone who hears it – hears it and sends us money. Lots of money.
The scene about favourite quotes to inspire entrepreneurs draws on this blog post from BigCommerce.
You probably already know all about the story of Juicero. That said, here's an update on CEO Doug Evens from Gizmodo.
You can find the Global Entrepreneurship Monitor report that says children should study entrepreneurship here, though we were consulting this Globe & Mail summary – even though they no longer employ any Allemangs, the bums!
If you enjoyed the Juicero movie trailer, you may like some of our other fake trailers: take the gritty Boss Baby reboot from episode 3, for instance, or Bobal Fett, Job Hunter from the job hunting episode.


Thought leadership is often used as a way of increasing or creating demand for a product or service. While thought leadership is not new, in our experience driven economy, where decisions about a brand are based off of who an organization is as much as what it does or sells, it has become an increasingly important vehicle to engage with both internal and external audiences.
This notion is particularly true and can have exponential impact, when an organization frames its thought leadership platform around an aspirational purpose; one which aims to give back to the world as much as the bottom-line, and does so in ways that give people a reason to believe and engage.


I arrived in Bangkok weighted down with good luck charms--my dad's Blarney Stone, my mother's rosary, a Nordic rune, a blessed Hindu scroll, a St. Christopher's medal. I'd covered all bets. So why was I so scared?
For years, the travel bug had been eating me alive. I was afraid to disturb my universe, but I'd finally become more afraid not to. Of all my fears, I realized, my biggest was regret. At 30, I was growing a little long in the tooth for the backpacking circuit, but if I didn't do it "now," I knew I never would. So I left my very good job, gave up my very nice apartment, sold all my stuff, and bought a one-way ticket to the other side of the world.
It was 2 a.m. when I landed. What had I done? The crazy, steaming city swirled and blared around me, the strange language honked and gabbled. I didn't understand the currency. It took two and a half hours to find my hotel, through dark streets strewn with stray dogs and slinking night people. But a kind man I met on the plane came with me, argued good-naturedly with the cabdriver in passable Thai, and saw me off with a smile and a wave. His unsolicited goodwill made me think I just might muddle through.
I used more Band-aids in those three months than in my entire adult life, a whole box, every size, a literal illustration of the difference between life at home and life "out there." My body was dotted purple, blue, and yellow from various stages of bruising. My wrists, knees, and elbows barely healed before the tender new skin was scraped off again, joining the old in the oblivion of jungle floor, dirt road, rocky beach.
And although I was losing a lifetime's accumulation of fears every day, some, tested, stuck around. I like to think of these fears as not just healthy, but positively Darwinian in their atavistic logic. It's good to be afraid of hand-sized cave spiders. They bite. They're bad. It's good to be afraid of the ocean. The ocean thinks of me as a piece of dust or a bit of food. I respect that. I wade. I dip. I paddle. I watch.
I amassed some new fears. It had never occurred to me to be afraid of jellyfish. There are no jellyfish at Wasaga Beach at home. But they are plentiful and painful in the clear, blue, Indian Ocean, and I don't want to be around them, nor the two-headed, very poisonous snake I saw while snorkeling for the first, and possibly last, time.


Nicole Kidman, Reese Witherspoon and co. won almost every prize they were nominated for.
Big Little Lies is officially this year's The People v OJ Simpson. The near-flawless HBO series swept this year's Emmy Awards, beating out competitors like Feud: Bette and Joan and Fargo to take home almost every single prize it was nominated for.
The series won the top Outstanding Limited Series prize, accepted by co-stars and co-producers Reese Witherspoon and Nicole Kidman. "Bring women to the front of their own stories," Kidman said, "and make them the hero of their own stories. And thank you for that opportunity and for audiences to wrap their arms around us." Her friendship with Witherspoon, she said, "created opportunities out of a frustration because we weren't getting offered great roles. So now, more great roles for women, please. Thank you." YES.
Jean-Marc Vallée won for Best Directing for a Limited Series, but longtime Emmy fave David E. Kelley missed out on the Best Writing prize, which went to Charlie Brooker for Black Mirror: San Junipero.
At the Creative Arts Emmys last weekend, Big Little Lies also won three awards for casting, music supervision and contemporary costumes. All in all, the show took home eight Emmys, which feels like as good an excuse as any to re-binge the entire series next weekend, TBH.