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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (4 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 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Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 6,434) Sort By: Publication Date Relevance Took: 3.049 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 258 1 2 3 4 > Last >> (6434 articles found) 'Good mentorship is invaluable' - an interview with Dr. Eugene P. DiMagno. Interview by Martin E. Fernandez-Zapico. 2005 Eugene P DiMagno Dr. DiMagno is internationally renowned for his contributions to almost all areas of pancreatology. He helped pioneer discoveries about normal pancreatic function, enzyme-based treatment of exocrine pancreatic insufficiency as well as methods of diagnosing pancreatitis and pancreatic cancer, includ... ( view more )ing the development of function tests and endoscopic ultrasound. Answering Martin Fernandez-Zapico's questions, he stresses the importance of good mentorship and gives us a glimpse of his life and work. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Parametric two-electron reduced-density-matrix method applied to computing molecular energies and properties at nonequilibrium geometries. Jun 21, 2008 A Eugene Deprince,Eugene Kamarchik,David A Mazziotti A parametric approach to the variational calculation of the two-electron reduced density matrix (2-RDM) for many-electron atoms and molecules has recently been developed in which the 2-RDM is parametrized to be both size consistent and nearly N-representable [C. Kollmar, J. Chem. Phys. 125, 084108 ... ( view more )(2006); A. E. DePrince and D. A. Mazziotti, Phys. Rev. A 76, 049903 (2007)]. The parametric variational 2-RDM method is applied to computing ground-state molecular energies and properties at nonequilibrium geometries in significantly larger basis sets than previously employed. We study hydrogen abstraction from the hydroxide groups of H(2)O, NH(3)OH, and CH(3)OH. The 2-RDM method, parametrized by single and double excitations, shows significant improvement over coupled-cluster methods with similar excitations in predicting the shape of potential energy curves and bond-dissociation energies. Previous work completes the parametrization of the energy and 2-RDM by a system of n(2)h(2) normalization constraints, where n and h are the number of occupied and unoccupied orbitals, respectively. In the present paper, however, we show that the constraints can be eliminated by incorporating them into the energy and 2-RDM functions and, hence, the constrained optimization of the ground-state energy can be reformulated as an unconstrained optimization. The 2-RDMs from the parametric method are very nearly N-representable, and as measured by an l(2) norm, they are more accurate than the 2-RDMs from configuration interaction truncated at single and double excitations by an order of magnitude. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A korarchaeal genome reveals insights into the evolution of the Archaea. Jun 10, 2008 James G Elkins,Mircea Podar,David E Graham,Kira S Makarova,Yuri Wolf,Lennart Randau,Brian P Hedlund,Céline Brochier-Armanet,Victor Kunin,Iain Anderson,Alla Lapidus,Eugene Goltsman,Kerrie Barry,Eugene V Koonin,Phil Hugenholtz,Nikos Kyrpides,Gerhard Wanner,Paul Richardson,Martin Keller,Karl O Stetter The candidate division Korarchaeota comprises a group of uncultivated microorganisms that, by their small subunit rRNA phylogeny, may have diverged early from the major archaeal phyla Crenarchaeota and Euryarchaeota. Here, we report the initial characterization of a member of the Korarchaeota with ... ( view more )the proposed name, "Candidatus Korarchaeum cryptofilum," which exhibits an ultrathin filamentous morphology. To investigate possible ancestral relationships between deep-branching Korarchaeota and other phyla, we used whole-genome shotgun sequencing to construct a complete composite korarchaeal genome from enriched cells. The genome was assembled into a single contig 1.59 Mb in length with a G + C content of 49%. Of the 1,617 predicted protein-coding genes, 1,382 (85%) could be assigned to a revised set of archaeal Clusters of Orthologous Groups (COGs). The predicted gene functions suggest that the organism relies on a simple mode of peptide fermentation for carbon and energy and lacks the ability to synthesize de novo purines, CoA, and several other cofactors. Phylogenetic analyses based on conserved single genes and concatenated protein sequences positioned the korarchaeote as a deep archaeal lineage with an apparent affinity to the Crenarchaeota. However, the predicted gene content revealed that several conserved cellular systems, such as cell division, DNA replication, and tRNA maturation, resemble the counterparts in the Euryarchaeota. In light of the known composition of archaeal genomes, the Korarchaeota might have retained a set of cellular features that represents the ancestral archaeal form. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration. Jan 21, 2008 Nicole A Morin,Patrick W Oakes,Young-Min Hyun,Dooyoung Lee,Y Eugene Chin,Eugene Y Chin,Michael R King,Timothy A Springer,Motomu Shimaoka,Jay X Tang,Jonathan S Reichner,Minsoo Kim Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function-associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesi... ( view more )on from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sample size and optimal design for logistic regression with binary interaction. Jan 15, 2008 Eugene Demidenko There is no consensus on what test to use as the basis for sample size determination and power analysis. Some authors advocate the Wald test and some the likelihood-ratio test. We argue that the Wald test should be used because the Z-score is commonly applied for regression coefficient significance... ( view more ) testing and therefore the same statistic should be used in the power function. We correct a widespread mistake on sample size determination when the variance of the maximum likelihood estimate (MLE) is estimated at null value. In our previous paper, we developed a correct sample size formula for logistic regression with single exposure (Statist. Med. 2007; 26(18):3385-3397). In the present paper, closed-form formulas are derived for interaction studies with binary exposure and covariate in logistic regression. The formula for the optimal control-case ratio is derived such that it maximizes the power function given other parameters. Our sample size and power calculations with interaction can be carried out online at www.dartmouth.edu/ approximately eugened. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Revisiting Lévy flight search patterns of wandering albatrosses, bumblebees and deer. Oct 25, 2007 Andrew M Edwards,Richard A Phillips,Nicholas W Watkins,Mervyn P Freeman,Eugene J Murphy,Vsevolod Afanasyev,Sergey V Buldyrev,M G E da Luz,E P Raposo,H Eugene Stanley,Gandhimohan M Viswanathan The study of animal foraging behaviour is of practical ecological importance, and exemplifies the wider scientific problem of optimizing search strategies. Lévy flights are random walks, the step lengths of which come from probability distributions with heavy power-law tails, such that clusters of ... ( view more )short steps are connected by rare long steps. Lévy flights display fractal properties, have no typical scale, and occur in physical and chemical systems. An attempt to demonstrate their existence in a natural biological system presented evidence that wandering albatrosses perform Lévy flights when searching for prey on the ocean surface. This well known finding was followed by similar inferences about the search strategies of deer and bumblebees. These pioneering studies have triggered much theoretical work in physics (for example, refs 11, 12), as well as empirical ecological analyses regarding reindeer, microzooplankton, grey seals, spider monkeys and fishing boats. Here we analyse a new, high-resolution data set of wandering albatross flights, and find no evidence for Lévy flight behaviour. Instead we find that flight times are gamma distributed, with an exponential decay for the longest flights. We re-analyse the original albatross data using additional information, and conclude that the extremely long flights, essential for demonstrating Lévy flight behaviour, were spurious. Furthermore, we propose a widely applicable method to test for power-law distributions using likelihood and Akaike weights. We apply this to the four original deer and bumblebee data sets, finding that none exhibits evidence of Lévy flights, and that the original graphical approach is insufficient. Such a graphical approach has been adopted to conclude Lévy flight movement for other organisms, and to propose Lévy flight analysis as a potential real-time ecosystem monitoring tool. Our results question the strength of the empirical evidence for biological Lévy flights. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles 5-(3-Cyclopentyl-2-thioxo-2,3-dihydro-1H-benzimidazol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile: A novel, highly potent, selective, and orally active non-steroidal progesterone receptor agonist. Oct 15, 2007 Puwen Zhang,Eugene Terefenko,Jeffrey Kern,Andrew Fensome,Eugene Trybulski,Ray Unwalla,Jay Wrobel,Susan Lockhead,Yuan Zhu,Jeffrey Cohen,Margaret Lacava,Richard C Winneker,Zhiming Zhang We have recently discovered 5-(3-cyclopentyl-2-thioxo-2,3-dihydro-1H-benzimidazol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile (14) as a potent, selective, and orally active non-steroidal progesterone receptor (PR) agonist. Compound 14 and its analog 13 possessed sub-nanomolar in vitro potency (EC(50) ... ( view more )0.1-0.5nM) in the T47D alkaline phosphatase assay, similar to that of the steroidal PR agonist medroxyprogesterone acetate (MPA). In contrast to MPA, 14 was highly selective (>500-fold) for the PR over both glucocorticoid and androgen receptors. In the rat uterine decidualization and complement component C3 models, 14 had oral ED(50) values of 0.02 and 0.003mg/kg, respectively, and was from 6- to 20-fold more potent than MPA. In the monkey ovulation inhibition model, compound 14 was also highly efficacious and potent with an oral ED(100) of 0.03mg/kg. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Sample size determination for logistic regression revisited. Aug 15, 2007 Eugene Demidenko There is no consensus on the approach to compute the power and sample size with logistic regression. Some authors use the likelihood ratio test; some use the test on proportions; some suggest various approximations to handle the multivariate case. We advocate the use of the Wald test since the Z-sc... ( view more )ore is routinely used for statistical significance testing of regression coefficients. The null-variance formula became popular from early studies, which contradicts modern software, which utilizes the method of maximum likelihood estimation (MLE), when the variance of the MLE is estimated at the MLE, not at the null. We derive general Wald-based power and sample size formulas for logistic regression and then apply them to binary exposure and confounder to obtain a closed-form expression. These formulas are applied to minimize the total sample size in a case-control study to achieve a given power by optimizing the ratio of controls to cases. Approximately, the optimal number of controls to cases is equal to the square root of the alternative odds ratio. Our sample size and power calculations can be carried out online at www.dartmouth.edu/ approximately eugened. ( view less ) View Full Abstract View Article Details   Related Articles A new preservation solution increases islet yield and reduces graft immunogenicity in pancreatic islet transplantation. May 27, 2007 Sebastien Giraud,Giraud Sebastien,Blandine Claire,Claire Blandine,Michel Eugene,Eugene Michel,Patrice Debre,Debre Patrice,François Richard,Richard François,Benoit Barrou,Barrou Benoit The aim of the study was to test a new preservation solution containing polyethylene glycol (S.C.O.T. solution) as pancreatic islet isolation medium both to increase the islet yield and to prolong the allograft survival. In a model of islet transplantation in diabetic mouse, islets were isolated wi... ( view more )th S.C.O.T. in experimental groups and with Hank's balanced salt solution (HBSS) in control groups. The use of S.C.O.T. solution improved the islet yield (596+/-27 IEQ/pancreas) as compared to HBSS (456+/-11 IEQ/pancreas) (P<0.001). Allograft survival was prolonged in experimental group (17.3+/-4.3 days) versus controls (7.3+/-3.6 days) in a full mismatch combination (P<0.001) and in absence of recipient immunosuppression. The same prolongation (10 days) was also found in a strongly alloreactive transgenic combination. It is hypothesized that a transitory phenomenon of immunocamouflage of the graft surface antigens occurs, as shown by immunofluorescence studies. The use of this new solution could improve the results of islet transplantation in humans. ( view less ) View Full Abstract View Article Details   Related Articles A structural and in vitro characterization of asoprisnil: a selective progesterone receptor modulator. May 2007 Kevin P Madauss,Eugene T Grygielko,Su-Jun Deng,Anthony C Sulpizio,Thomas B Stanley,Charlene Wu,Steve A Short,Scott K Thompson,Eugene L Stewart,Nicholas J Laping,Shawn P Williams,Jeffrey D Bray Selective progesterone receptor modulators (SPRMs) have been suggested as therapeutic agents for treatment of gynecological disorders. One such SPRM, asoprisnil, was recently in clinical trials for treatment of uterine fibroids and endometriosis. We present the crystal structures of progesterone re... ( view more )ceptor (PR) ligand binding domain complexed with asoprisnil and the corepressors nuclear receptor corepressor (NCoR) and SMRT. This is the first report of steroid nuclear receptor crystal structures with ligand and corepressors. These structures show PR in a different conformation than PR complexed with progesterone (P4). We profiled asoprisnil in PR-dependent assays to understand further the PR-mediated mechanism of action. We confirmed previous findings that asoprisnil demonstrated antagonism, but not agonism, in a PR-B transfection assay and the T47D breast cancer cell alkaline phosphatase activity assay. Asoprisnil, but not RU486, weakly recruited the coactivators SRC-1 and AIB1. However, asoprisnil strongly recruited the corepressor NCoR in a manner similar to RU486. Unlike RU486, NCoR binding to asoprisnil-bound PR could be displaced with equal affinity by NCoR or TIF2 peptides. We further showed that it weakly activated T47D cell gene expression of Sgk-1 and PPL and antagonized P4-induced expression of both genes. In rat leiomyoma ELT3 cells, asoprisnil demonstrated partial P4-like inhibition of cyclooxygenase (COX) enzymatic activity and COX-2 gene expression. In the rat uterotrophic assay, asoprisnil demonstrated no P4-like ability to oppose estrogen. Our data suggest that asoprisnil differentially recruits coactivators and corepressors compared to RU486 or P4, and this specific cofactor interaction profile is apparently insufficient to oppose estrogenic activity in rat uterus. ( view less ) View Full Abstract View Article Details   Related Articles Identification and mapping of open chromatin regions within a 140 kb polygenic locus of human chromosome 19 using E. coli Dam methylase. May 2007 Svetlana Bulanenkova,Eugene Snezhkov,Lev Nikolaev,Eugene Sverdlov Using transient expression of the E. coli Dam methylase gene and analysis of the distribution of methylated GATC sites, we studied the distribution of open chromatin regions within a 140 kb long human genome segment in HEK-293 cells. Dam methylated sites were found in gene introns, exons, and inter... ( view more )genic regions, and their distribution along DNA was uneven. There were regions of high and low density of Dam methylated GATC sites, presumably corresponding to "open" and "closed" chromatin regions, respectively, and to the functional profile of the genomic locus under study. The Dam methylation profile was also generally in agreement with transcriptional activity of genes in the locus. Moreover, DNA regions accessible to Dam methylase apparently coincided with those hypersensitive to DNase I. ( view less ) View Full Abstract View Article Details   Related Articles Comparison of protective effects of trimetazidine against experimental warm ischemia of different durations: early and long-term effects in a pig kidney model. Mar 2007 Christophe Jayle,Frederic Favreau,Kequiang Zhang,Carole Doucet,Jean Michel Goujon,William Hebrard,Michel Carretier,Michel Eugene,Gerard Mauco,Jean Paul Tillement,Thierry Hauet Acute renal failure (ARF) is often the consequence of an ischemia-reperfusion injury (IRI) and associated with high mortality. Warm ischemia (WI) is a crucial factor of tissue damage, and tissue destruction led by ischemia-reperfusion (I/R) can impact the early and long-term functional outcome. Tri... ( view more )metazidine (TMZ) is an anti-ischemic drug. Previously, we already verified its protective effect on a cold-ischemic pig kidney model by directly adding TMZ into the preservation solution (Faure JP, Baumert H, Han Z, Goujon JM, Favreau F, Dutheil D, Petit I, Barriere M, Tallineau C, Tillement JP, Carretier M, Mauco G, Papadopoulos V, Hauet T. Biochem Pharmacol 66: 2241-2250, 2003; Faure JP, Petit I, Zhang K, Dutheil D, Doucet C, Favreau F, Eugene M, Goujon JM, Tillement JP, Mauco G, Vandewalle A, Hauet T. Am J Transplant 4: 495-504, 2004). In this study, we aimed to study the potential effect of TMZ pretreatment (5 mg/kg iv 24 h before WI) on the injury caused by WI for 45, 60, and 90 min and reperfusion in a WI pig kidney model. Compared with sham-operated (control) and uninephrectomized animals (UNX), TMZ pretreatment significantly reduced deleterious effects after 45 min, and particularly 60 and 90 min, of WI by improving the recovery of renal function and minimizing the inflammatory response commonly prevalent in ischemic kidney injury. Compared with controls (control group and UNX group), it was observed that 1) hypoxia-inducible factor-1 (HIF-1alpha) expression occurred earlier and with a higher intensity in the TMZ-treated groups; 2) the reduction of IRI during the first week following reperfusion was correlated with an earlier and greater expression of stathmin, which is involved in the process of tubular repair; and 3) the tubulointerstitial fibrosis was reduced, particularly after 60 and 90 min of WI. In conclusion, TMZ made the warm-ischemic kidneys more resistant to the deleterious impact of a single episode of I/R and reduced early and long-term subsequent damage. ( view less ) View Full Abstract View Article Details   Related Articles Characterization of E-cadherin-dependent and -independent events in a new model of c-Fos-mediated epithelial-mesenchymal transition. Jan 15, 2007 Jakob Mejlvang,Marina Kriajevska,Fedor Berditchevski,Igor Bronstein,Eugene M Lukanidin,J Howard Pringle,J Kilian Mellon,Eugene M Tulchinsky Fos proteins have been implicated in control of tumorigenesis-related genetic programs including invasion, angiogenesis, cell proliferation and apoptosis. In this study, we demonstrate that c-Fos is able to induce mesenchymal transition in murine tumorigenic epithelial cell lines. Expression of c-F... ( view more )os in MT1TC1 cells led to prominent alterations in cell morphology, increased expression of mesenchymal markers, vimentin and S100A4, DNA methylation-dependent down-regulation of E-cadherin and abrogation of cell-cell adhesion. In addition, c-Fos induced a strong beta-catenin-independent proliferative response in MT1TC1 cells and stimulated cell motility, invasion and adhesion to different extracellular matrix proteins. To explore whether loss of E-cadherin plays a role in c-Fos-mediated mesenchymal transition, we expressed wild-type E-cadherin and two different E-cadherin mutants in MT1TC1/c-fos cells. Expression of wild-type E-cadherin restored epithelioid morphology and enhanced cellular levels of catenins. However, exogenous E-cadherin did not influence expression of c-Fos-dependent genes, only partly suppressed growth of MT1TC1/c-fos cells and produced no effect on c-Fos-stimulated cell motility and invasion in matrigel. On the other hand, re-expression of E-cadherin specifically negated c-Fos-induced adhesion to collagen type I, but not to laminin or fibronectin. Of interest, mutant E-cadherin which lacks the ability to form functional adhesive complexes had an opposite, potentiating effect on cell adhesion to collagen I. These data suggest that cell adhesion to collagen I is regulated by the functional state of E-cadherin. Overall, our data demonstrate that, with the exception of adhesion to collagen I, c-Fos is dominant over E-cadherin in relation to the aspects of mesenchymal transition assayed in this study. ( view less ) View Full Abstract View Article Details   Related Articles Tuning of a neuronal calcium sensor. Dec 8, 2006 Oliver H Weiergräber,Ivan I Senin,Eugene Yu Zernii,Valeriya A Churumova,Nadezhda A Kovaleva,Aliya A Nazipova,Sergei E Permyakov,Eugene A Permyakov,Pavel P Philippov,Joachim Granzin,Karl-Wilhelm Koch Recoverin is a Ca(2+)-regulated signal transduction modulator expressed in the vertebrate retina that has been implicated in visual adaptation. An intriguing feature of recoverin is a cluster of charged residues at its C terminus, the functional significance of which is largely unclear. To elucidat... ( view more )e the impact of this segment on recoverin structure and function, we have investigated a mutant lacking the C-terminal 12 amino acids. Whereas in myristoylated recoverin the truncation causes an overall decrease in Ca(2+) sensitivity, results for the non-myristoylated mutant indicate that the truncation primarily affects the high affinity EF-hand 3. The three-dimensional structure of the mutant has been determined by x-ray crystallography. In addition to significant changes in average coordinates compared with wild-type recoverin, the structure provides strong indication of increased conformational flexibility, particularly in the C-terminal domain. Based on these observations, we propose a novel role of the C-terminal segment of recoverin as an internal modulator of Ca(2+) sensitivity. ( view less ) View Full Abstract View Article Details   Related Articles Surfaces and interfacial water: evidence that hydrophilic surfaces have long-range impact. Nov 23, 2006 Jian-Ming Zheng,Wei-Chun Chin,Eugene Khijniak,Eugene Khijniak,Gerald H Pollack It is generally thought that the impact of surfaces on the contiguous aqueous phase extends to a distance of no more than a few water-molecule layers. Older studies, on the other hand, suggest a more extensive impact. We report here that colloidal and molecular solutes suspended in aqueous solution... ( view more ) are profoundly and extensively excluded from the vicinity of various hydrophilic surfaces. The width of the solute-free zone is typically several hundred microns. Such large exclusion zones were observed in the vicinity of many types of surface including artificial and natural hydrogels, biological tissues, hydrophilic polymers, monolayers, and ion-exchange beads, as well as with a variety of solutes. Using microscopic observations, as well as measurements of electrical potential and UV-Vis absorption-spectra, infrared imaging, and NMR imaging, we find that the solute-free zone is a physically distinct and less mobile phase of water that can co-exist indefinitely with the contiguous solute-containing phase. The extensiveness of this modified zone is impressive, and carries broad implication for surface-molecule interactions in many realms, including cellular recognition, biomaterial-surface antifouling, bioseparation technologies, and other areas of biology, physics and chemistry. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The MicroArray Quality Control (MAQC) project shows inter- and intraplatform reproducibility of gene expression measurements. Sep 2006 MAQC Consortium ,Leming Shi,Laura H Reid,Wendell D Jones,Richard Shippy,Janet A Warrington,Shawn C Baker,Patrick J Collins,Francoise de Longueville,Ernest S Kawasaki,Kathleen Y Lee,Yuling Luo,Yongming Andrew Sun,James C Willey,Robert A Setterquist,Gavin M Fischer,Weida Tong,Yvonne P Dragan,David J Dix,Felix W Frueh,Frederico M Goodsaid,Damir Herman,Roderick V Jensen,Charles D Johnson,Edward K Lobenhofer,Raj K Puri,Uwe Schrf,Jean Thierry-Mieg,Charles Wang,Mike Wilson,Paul K Wolber,Lu Zhang,Shashi Amur,Wenjun Bao,Catalin C Barbacioru,Anne Bergstrom Lucas,Vincent Bertholet,Cecilie Boysen,Bud Bromley,Donna Brown,Alan Brunner,Roger Canales,Xiaoxi Megan Cao,Thomas A Cebula,James J Chen,Jing Cheng,Tzu-Ming Chu,Eugene Chudin,John Corson,J Christopher Corton,Lisa J Croner,Christopher Davies,Timothy S Davison,Glenda Delenstarr,Xutao Deng,David Dorris,Aron C Eklund,Xiao-hui Fan,Hong Fang,Stephanie Fulmer-Smentek,James C Fuscoe,Kathryn Gallagher,Weigong Ge,Lei Guo,Xu Guo,Janet Hager,Paul K Haje,Jing Han,Tao Han,Heather C Harbottle,Stephen C Harris,Eli Hatchwell,Craig A Hauser,Susan Hester,Huixiao Hong,Patrick Hurban,Scott A Jackson,Hanlee Ji,Charles R Knight,Winston P Kuo,J Eugene LeClerc,Shawn Levy,Quan-Zhen Li,Chunmei Liu,Ying Liu,Michael J Lombardi,Yunqing Ma,Scott R Magnuson,Botoul Maqsodi,Tim McDaniel,Nan Mei,Ola Myklebost,Baitang Ning,Natalia Novoradovskaya,Michael S Orr,Terry W Osborn,Adam Papallo,Tucker A Patterson,Roger G Perkins,Elizabeth H Peters,Ron Peterson,Kenneth L Philips,P Scott Pine,Lajos Pusztai,Feng Qian,Hongzu Ren,Mitch Rosen,Barry A Rosenzweig,Raymond R Samaha,Mark Schena,Gary P Schroth,Svetlana Shchegrova,Dave D Smith,Frank Staedtler,Zhenqiang Su,Hongmei Sun,Zoltan Szallasi,Zivana Tezak,Danielle Thierry-Mieg,Karol L Thompson,Irina Tikhonova,Yaron Turpaz,Beena Vallanat,Christophe Van,Stephen J Walker,Sue Jane Wang,Yonghong Wang,Russ Wolfinger,Alex Wong,Jie Wu,Chunlin Xiao,Qian Xie,Jun Xu,Wen Yang,Liang Zhang,Sheng Zhong,Yaping Zong,William Slikker Over the last decade, the introduction of microarray technology has had a profound impact on gene expression research. The publication of studies with dissimilar or altogether contradictory results, obtained using different microarray platforms to analyze identical RNA samples, has raised concerns ... ( view more )about the reliability of this technology. The MicroArray Quality Control (MAQC) project was initiated to address these concerns, as well as other performance and data analysis issues. Expression data on four titration pools from two distinct reference RNA samples were generated at multiple test sites using a variety of microarray-based and alternative technology platforms. Here we describe the experimental design and probe mapping efforts behind the MAQC project. We show intraplatform consistency across test sites as well as a high level of interplatform concordance in terms of genes identified as differentially expressed. This study provides a resource that represents an important first step toward establishing a framework for the use of microarrays in clinical and regulatory settings. ( view less ) View Full Abstract View Article Details   Related Articles B7-H4 expression in renal cell carcinoma and tumor vasculature: associations with cancer progression and survival. Jul 5, 2006 Amy E Krambeck,R Houston Thompson,Haidong Dong,Christine M Lohse,Eugene S Park,Susan M Kuntz,Bradley C Leibovich,Michael L Blute,John C Cheville,Eugene D Kwon B7-H4 is a recently described B7 family coregulatory ligand that has been implicated as an inhibitor of T cell-mediated immunity. Although expression of B7-H4 is typically limited to lymphoid cells, aberrant B7-H4 expression has also been reported in several human malignancies. To date, association... ( view more )s of B7-H4 with clinical outcomes for cancer patients are lacking. Therefore, we examined B7-H4 expression in fresh-frozen tumor specimens from 259 renal cell carcinoma (RCC) patients treated with nephrectomy between 2000 and 2003 and performed correlative outcome analyses. We report that 153 (59.1%) RCC tumor specimens exhibited B7-H4 staining and that tumor cell B7-H4 expression was associated with adverse clinical and pathologic features, including constitutional symptoms, tumor necrosis, and advanced tumor size, stage, and grade. Patients with tumors expressing B7-H4 were also three times more likely to die from RCC compared with patients lacking B7-H4 (risk ratio = 3.05; 95% confidence interval = 1.51-6.14; P = 0.002). Additionally, 211 (81.5%) specimens exhibited tumor vasculature endothelial B7-H4 expression, whereas only 6.5% of normal adjacent renal tissue vessels exhibited endothelial B7-H4 staining. Based on these findings, we conclude that B7-H4 has the potential to be a useful prognostic marker for patients with RCC. In addition, B7-H4 represents a target for attacking tumor cells as well as tumor neovasculature to facilitate immunotherapeutic treatment of RCC tumors. Last, we demonstrate that patients with RCC tumors expressing both B7-H4 and B7-H1 are at an even greater risk of death from RCC. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A combined approach to drug metabolism and toxicity assessment. Mar 2006 Sean Ekins,Sergey Andreyev,Andy Ryabov,Eugene Kirillov,Eugene A Rakhmatulin,Svetlana Sorokina,Andrej Bugrim,Tatiana Nikolskaya The challenge of predicting the metabolism or toxicity of a drug in humans has been approached using in vivo animal models, in vitro systems, high throughput genomics and proteomics methods, and, more recently, computational approaches. Understanding the complexity of biological systems requires a ... ( view more )broader perspective rather than focusing on just one method in isolation for prediction. Multiple methods may therefore be necessary and combined for a more accurate prediction. In the field of drug metabolism and toxicology, we have seen the growth, in recent years, of computational quantitative structure-activity relationships (QSARs), as well as empirical data from microarrays. In the current study we have further developed a novel computational approach, MetaDrug, that 1) predicts metabolites for molecules based on their chemical structure, 2) predicts the activity of the original compound and its metabolites with various absorption, distribution, metabolism, excretion, and toxicity models, 3) incorporates the predictions with human cell signaling and metabolic pathways and networks, and 4) integrates networks and metabolites, with relevant toxicogenomic or other high throughput data. We have demonstrated the utility of such an approach using recently published data from in vitro metabolism and microarray studies for aprepitant, 2(S)-((3,5-bis(trifluoromethyl)benzyl)-oxy)-3(S)phenyl-4-((3-oxo-1,2,4-triazol-5-yl)methyl)morpholine (L-742694), trovofloxacin, 4-hydroxytamoxifen, and artemisinin and other artemisinin analogs to show the predicted interactions with cytochromes P450, pregnane X receptor, and P-glycoprotein, and the metabolites and the networks of genes that are affected. As a comparison, we used a second computational approach, MetaCore, to generate statistically significant gene networks with the available expression data. These case studies demonstrate the combination of QSARs and systems biology methods. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Immediate and delayed effects of E-cadherin inhibition on gene regulation and cell motility in human epidermoid carcinoma cells. Oct 2005 Henriette Andersen,Jakob Mejlvang,Shaukat Mahmood,Irina Gromova,Pavel Gromov,Eugene Lukanidin,Marina Kriajevska,J Kilian Mellon,Eugene Tulchinsky The invasion suppressor protein, E-cadherin, plays a central role in epithelial cell-cell adhesion. Loss of E-cadherin expression or function in various tumors of epithelial origin is associated with a more invasive phenotype. In this study, by expressing a dominant-negative mutant of E-cadherin (E... ( view more )c1WVM) in A431 cells, we demonstrated that specific inhibition of E-cadherin-dependent cell-cell adhesion led to the genetic reprogramming of tumor cells. In particular, prolonged inhibition of cell-cell adhesion activated expression of vimentin and repressed cytokeratins, suggesting that the effects of Ec1WVM can be classified as epithelial-mesenchymal transition. Both short-term and prolonged expression of Ec1WVM resulted in morphological transformation and increased cell migration though to different extents. Short-term expression of Ec1WVM up-regulated two AP-1 family members, c-jun and fra-1, but was insufficient to induce complete mesenchymal transition. AP-1 activity induced by the short-term expression of Ec1WVM was required for transcriptional up-regulation of AP-1 family members and down-regulation of two other Ec1WVM-responsive genes, S100A4 and igfbp-3. Using a dominant-negative mutant of c-Jun (TAM67) and RNA interference-mediated silencing of c-Jun and Fra-1, we demonstrated that AP-1 was required for cell motility stimulated by the expression of Ec1WVM. In contrast, Ec1WVM-mediated changes in cell morphology were AP-1-independent. Our data suggest that mesenchymal transition induced by prolonged functional inhibition of E-cadherin is a slow and gradual process. At the initial step of this process, Ec1WVM triggers a positive autoregulatory mechanism that increases AP-1 activity. Activated AP-1 in turn contributes to Ec1WVM-mediated effects on gene expression and tumor cell motility. These data provide novel insight into the tumor suppressor function of E-cadherin. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Support services key to IT maintenance. Sep 2005 Eugene Conroy The vital role of support services in ensuring the smooth operation of NHS IT networks is outlined by Eugene Conroy CEng, electrical director, Eta Projects, who goes on to provide an overview of the IT upgrade works at The Hammersmith Hospital NHS Trust. View Full Abstract View Article Details View Coded Data Related Articles Computational prediction of human drug metabolism. Aug 2005 Sean Ekins,Sergey Andreyev,Andy Ryabov,Eugene Kirillov,Eugene A Rakhmatulin,Andrej Bugrim,Tatiana Nikolskaya There is an urgent requirement within the pharmaceutical and biotechnology industries, regulatory authorities and academia to improve the success of molecules that are selected for clinical trials. Although absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) properties are some ... ( view more )of the many components that contribute to successful drug discovery and development, they represent factors for which we currently have in vitro and in vivo data that can be modelled computationally. Understanding the possible toxicity and the metabolic fate of xenobiotics in the human body is particularly important in early drug discovery. There is, therefore, a need for computational methodologies for uncovering the relationships between the structure and the biological activity of novel molecules. The convergence of numerous technologies, including high-throughput techniques, databases, ADME/Tox modelling and systems biology modelling, is leading to the foundation of systems-ADME/Tox. Results from experiments can be integrated with predictions to globally simulate and understand the likely complete effects of a molecule in humans. The development and early application of major components of MetaDrug (GeneGo, Inc.) software will be described, which includes rule-based metabolite prediction, quantitative structure-activity relationship models for major drug metabolising enzymes, and an extensive database of human protein-xenobiotic interactions. This represents a combined approach to predicting drug metabolism. MetaDrug can be readily used for visualising Phase I and II metabolic pathways, as well as interpreting high-throughput data derived from microarrays as networks of interacting objects. This will ultimately aid in hypothesis generation and the early triaging of molecules likely to have undesirable predicted properties or measured effects on key proteins and cellular functions. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium. Jul 15, 2005 Shasi V Kalivendi,Eugene A Konorev,Sonya Cunningham,Sravan K Vanamala,Eugene H Kaji,Joy Joseph,B Kalyanaraman Doxorubicin (DOX), a widely used antitumour drug, causes dose-dependent cardiotoxicity. Cardiac mitochondria represent a critical target organelle of toxicity during DOX chemotherapy. Proposed mechanisms include generation of ROS (reactive oxygen species) and disturbances in mitochondrial calcium h... ( view more )omoeostasis. In the present study, we probed the mechanistic link between mitochondrial ROS and calcium in the embryonic rat heart-derived H9c2 cell line and in adult rat cardiomyocytes. The results show that DOX stimulates calcium/calcineurin-dependent activation of the transcription factor NFAT (nuclear factor of activated T-lymphocytes). Pre-treatment of cells with an intracellular calcium chelator abrogated DOX-induced nuclear NFAT translocation, Fas L (Fas ligand) expression and caspase activation, as did pre-treatment of cells with a mitochondria-targeted antioxidant, Mito-Q (a mitochondria-targeted antioxidant consisting of a mixture of mitoquinol and mitoquinone), or with adenoviral-over-expressed antioxidant enzymes. Treatment with GPx-1 (glutathione peroxidase 1), MnSOD (manganese superoxide dismutase) or a peptide inhibitor of NFAT also inhibited DOX-induced nuclear NFAT translocation. Pre-treatment of cells with a Fas L neutralizing antibody abrogated DOX-induced caspase-8- and -3-like activities during the initial stages of apoptosis. We conclude that mitochondria-derived ROS and calcium play a key role in stimulating DOX-induced 'intrinsic and extrinsic forms' of apoptosis in cardiac cells with Fas L expression via the NFAT signalling mechanism. Implications of ROS- and calcium-dependent NFAT signalling in DOX-induced apoptosis are discussed. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The Wolbachia genome of Brugia malayi: endosymbiont evolution within a human pathogenic nematode. Apr 2005 Jeremy Foster,Mehul Ganatra,Ibrahim Kamal,Jennifer Ware,Kira Makarova,Natalia Ivanova,Anamitra Bhattacharyya,Vinayak Kapatral,Sanjay Kumar,Janos Posfai,Tamas Vincze,Jessica Ingram,Laurie Moran,Alla Lapidus,Marina Omelchenko,Nikos Kyrpides,Elodie Ghedin,Shiliang Wang,Eugene Goltsman,Victor Joukov,Olga Ostrovskaya,Kiryl Tsukerman,Mikhail Mazur,Donald Comb,Eugene Koonin,Barton Slatko Complete genome DNA sequence and analysis is presented for Wolbachia, the obligate alpha-proteobacterial endosymbiont required for fertility and survival of the human filarial parasitic nematode Brugia malayi. Although, quantitatively, the genome is even more degraded than those of closely related ... ( view more )Rickettsia species, Wolbachia has retained more intact metabolic pathways. The ability to provide riboflavin, flavin adenine dinucleotide, heme, and nucleotides is likely to be Wolbachia's principal contribution to the mutualistic relationship, whereas the host nematode likely supplies amino acids required for Wolbachia growth. Genome comparison of the Wolbachia endosymbiont of B. malayi (wBm) with the Wolbachia endosymbiont of Drosophila melanogaster (wMel) shows that they share similar metabolic trends, although their genomes show a high degree of genome shuffling. In contrast to wMel, wBm contains no prophage and has a reduced level of repeated DNA. Both Wolbachia have lost a considerable number of membrane biogenesis genes that apparently make them unable to synthesize lipid A, the usual component of proteobacterial membranes. However, differences in their peptidoglycan structures may reflect the mutualistic lifestyle of wBm in contrast to the parasitic lifestyle of wMel. The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems. Analysis of this first sequenced endosymbiont genome from a filarial nematode provides insight into endosymbiont evolution and additionally provides new potential targets for elimination of cutaneous and lymphatic human filarial disease. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles A novel method for visualizing nuclear hormone receptor networks relevant to drug metabolism. Mar 2005 Sean Ekins,Eugene Kirillov,Eugene A Rakhmatulin,Tatiana Nikolskaya The increasing generation of biological data represents a challenge to understanding the complexity of systems, resulting in scientists increasingly focused on a relatively narrow area of study, thereby limiting insight that can be gained from a broader perspective. In the field of drug metabolism ... ( view more )and toxicology we are witnessing the characterization of many proteins. Most of the key enzymes and transporters are recognized as transcriptionally regulated by the nuclear hormone receptors such as pregnane X receptor, constitutive androstane receptor, vitamin D receptor, glucocorticoid receptor, and others. There is apparent cross talk in regulation, since multiple receptors may modulate expression of a single enzyme or transporter, representing one of many areas of active research interest. We have used published data on nuclear hormone receptors, enzymes, ligands, and other biological information to manually annotate an Oracle database, forming the basis of a platform for querying (MetaDrug). Using algorithms, we have demonstrated how nuclear hormone receptors alone can form a network of direct interactions, and when expanded, this network increases in complexity to describe the interactions with target genes as well as small molecules known to bind a receptor, enzyme, or transporter. We have also described how the database can be used for visualizing high-throughput microarray data derived from a published study of MCF-7 cells treated with 4-hydroxytamoxifen, to highlight potential downstream effects of molecule treatment. The database represents a novel knowledge mining and analytical tool that, to be relevant, requires continual updating to evolve alongside other key storage systems and sources of biological knowledge. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The hefty penalty on marriage facing many households with children. 2005 Adam Carasso,C Eugene Steuerle Over the past seventy years Congress has enacted dozens of tax and transfer programs, giving little if any attention to the marriage subsidies and penalties that they inadvertently impose. Although the programs affect both rich and poor Americans, the penalties fall most heavily on low- or moderate... ( view more )-income households with children. In this article, Adam Carasso and Eugene Steuerle review important penalties and subsidies, explain how they work, and help fill a big research gap by beginning to provide comprehensive data on the size of the penalties and subsidies arising from all public programs considered together. Marriage penalties arise because of the combination of variable U.S. tax rates and joint, rather than individual, filing by married couples for benefits and taxes. If graduated taxes were accompanied by individual filing or if all income and transfers were taxed at a flat rate, there would be no marriage penalties. Specifically, the penalties are a result of policymakers' efforts to achieve the goal of progressivity--giving greater tax and welfare benefits to those with lower income--while trying to keep down program costs. Thus benefits in transfer programs fall, sometimes steeply, as households earn more income. Combining the direct tax rate in the tax code and the benefit reduction rates in the transfer system can result in extremely high effective marginal tax rates for many low- to moderate-income families-rates far higher than those of families earning over 90,000 dollars. These high rates lead to the marriage penalties because additional income brought into a household by marriage thus causes other benefits to be reduced or lost altogether. In extreme cases, households can lose a dollar or more for every dollar earned. In recent years lawmakers have begun to try to reduce marriage penalties, primarily by reforming welfare and cutting taxes, but huge penalties remain. The authors offer several options for reducing or eliminating the marriage penalty and recommend two in particular. The first is to set a maximum marginal tax rate for lower-income individuals, similar to the maximum rate set for highest-income individuals. The second is to provide individual wage subsidies to lower-income earners, so that such workers who marry can combine their income with that of their spouse without incurring penalties. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 258 1 2 3 4 > Last >> (6434 articles found)

      
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