bluuebunny/crossref_metadata_2025_split huggingface dataset:
GW501516-activated PPARβ/δ promotes liver fibrosis via p38-JNK MAPK-induced hepatic stellate cell proliferation
Authors: Kostadinova Radina , Montagner Alexandra , Gouranton Erwan , Fleury Sébastien , Guillou Hervé , Dombrowicz David , Desreumaux Pierre , Wahli Walter 
Published: October 2012

Abstract

Background
After liver injury, the repair process comprises activation and proliferation of hepatic stellate cells (HSCs), which produce extracellular matrix (ECM) proteins. Peroxisome proliferator-activated receptor beta/delta ( PPARβ/δ) is highly expressed in these cells, but its function in liver repair remains incompletely understood. This study investigated whether activation of PPARβ/δ with the ligand GW501516 influenced the fibrotic response to injury from chronic carbon tetrachloride (CCl4) treatment in mice. Wild type and PPARβ/δ-null mice were treated with CCl4 alone or CCl4 co-administered with GW501516. To unveil mechanisms underlying the PPARβ/δ-dependent effects, we analyzed the proliferative response of human LX-2 HSCs to GW501516 in the presence or absence of PPARβ/δ.

Results
We found that GW501516 treatment enhanced the fibrotic response. Compared to the other experimental groups, CCl4/GW501516-treated wild type mice exhibited increased expression of various profibrotic and pro-inflammatory genes, such as those involved in extracellular matrix deposition and macrophage recruitment. Importantly, compared to healthy liver, hepatic fibrotic tissues from alcoholic patients showed increased expression of several PPAR target genes, including phosphoinositide-dependent kinase-1, transforming growth factor beta-1, and monocyte chemoattractant protein-1. GW501516 stimulated HSC proliferation that caused enhanced fibrotic and inflammatory responses, by increasing the phosphorylation of p38 and c-Jun N-terminal kinases through the phosphoinositide-3 kinase/protein kinase-C alpha/beta mixed lineage kinase-3 pathway.

Conclusions
This study clarified the mechanism underlying GW501516-dependent promotion of hepatic repair by stimulating proliferation of HSCs via the p38 and JNK MAPK pathways.
Dehalogenimonas spp. can Reductively Dehalogenate High Concentrations of 1,2-Dichloroethane, 1,2-Dichloropropane, and 1,1,2-Trichloroethane
Authors: Maness Andrew D , Bowman Kimberly S , Yan Jun , Rainey Fred A , Moe William M 
Published: October 2012

Abstract
The contaminant concentrations over which type strains of the species Dehalogenimonas alkenigignens and Dehalogenimonas lykanthroporepellens were able to reductively dechlorinate 1,2-dichloroethane (1,2-DCA), 1,2-dichloropropane (1,2-DCP), and 1,1,2-trichloroethane (1,1,2-TCA) were evaluated. Although initially isolated from an environment with much lower halogenated solvent concentrations, D. alkenigignens IP3-3T was found to reductively dehalogenate chlorinated alkanes at concentrations comparable to D. lykanthroporepellens BL-DC-9T. Both species dechlorinated 1,2-DCA, 1,2-DCP, and 1,1,2-TCA present at initial concentrations at least as high as 8.7, 4.0, and 3.5 mM, respectively. The ability of Dehalogenimonas spp. to carry out anaerobic reductive dechlorination even in the presence of high concentrations of chlorinated aliphatic alkanes has important implications for remediation of contaminated soil and groundwater.
The use of cognitive ability measures as explanatory variables in regression analysis
Authors: Junker Brian , Schofield Lynne Steuerle , Taylor Lowell J 
Published: October 2012

Abstract

Abstract
Cognitive ability measures are often taken as explanatory variables in regression analysis, e.g., as a factor affecting a market outcome such as an individual’s wage, or a decision such as an individual’s education acquisition. Cognitive ability is a latent construct; its true value is unobserved. Nonetheless, researchers often assume that a test score, constructed via standard psychometric practice from individuals’ responses to test items, can be safely used in regression analysis. We examine problems that can arise, and suggest that an alternative approach, a “mixed effects structural equations” (MESE) model, may be more appropriate in many circumstances.

JEL Code
J01
Unintended Consequences of Health Information Technology: Evidence From Veterans Affairs Colorectal Cancer Oncology Watch Intervention
Authors: Bian John , Bennett Charles L. , Fisher Deborah A. , Ribeiro Maria , Lipscomb Joseph 
Published: October 2012

Purpose We evaluated the Colorectal Cancer (CRC) Oncology Watch intervention, a clinical reminder implemented in Veterans Integrated Service Network 7 (including eight hospitals) to improve CRC screening rates in 2008. Patients and Methods Veterans Affairs (VA) administrative data were used to construct four cross-sectional groups of veterans at average risk, age 50 to 64 years; one group was created for each of the following years: 2006, 2007, 2009, and 2010. We applied hospital fixed effects for estimation, using a difference-in-differences model in which the eight hospitals served as the intervention sites, and the other 121 hospitals served as controls, with 2006 to 2007 as the preintervention period and 2009 to 2010 as the postintervention period. Results The sample included 4,352,082 veteran-years in the 4 years. The adherence rates were 37.6%, 31.6%, 34.4%, and 33.2% in the intervention sites in 2006, 2007, 2009, and 2010, respectively, and the corresponding rates in the controls were 31.0%, 30.3%, 32.3%, and 30.9%. Regression analysis showed that among those eligible for screening, the intervention was associated with a 2.2–percentage point decrease in likelihood of adherence (P < .001). Additional analyses showed that the intervention was associated with a 5.6–percentage point decrease in likelihood of screening colonoscopy among the adherent, but with increased total colonoscopies (all indicators) of 3.6 per 100 veterans age 50 to 64 years. Conclusion The intervention had little impact on CRC screening rates for the studied population. This absence of favorable impact may have been caused by an unintentional shift of limited VA colonoscopy capacity from average-risk screening to higher-risk screening and to CRC surveillance, or by physician fatigue resulting from the large number of clinical reminders implemented in the VA.
Stage-Adapted Treatment of HIV-Associated Hodgkin Lymphoma: Results of a Prospective Multicenter Study
Authors: Hentrich Marcus , Berger Marcel , Wyen Christoph , Siehl Jan , Rockstroh Jürgen K. , Müller Markus , Fätkenheuer Gerd , Seidel Elisabeth , Nickelsen Maike , Wolf Timo , Rieke Ansgar , Schürmann Dirk , Schmidmaier Ralf , Planker Manfred , Alt Jürgen , Mosthaf Franz , Engert Andreas , Arasteh Keikawus , Hoffmann Christian 
Published: October 2012

Purpose Although the outcome of patients with HIV-related Hodgkin lymphoma (HIV-HL) has markedly improved since the introduction of combined antiretroviral therapy, standard therapy is still poorly defined. This prospective study investigates a stage- and risk-adapted treatment strategy in patients with HIV-HL. Patients and Methods Patients with early favorable HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of involved-field (IF) radiation. In patients with early unfavorable HIV-HL, four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP baseline) or four cycles of ABVD + 30 Gy of IF radiation were administered. Six to eight cycles of BEACOPP baseline were given in patients with advanced-stage HIV-HL. In patients with advanced HIV infection, BEACOPP was replaced with ABVD. Results Of 108 patients (including eight female patients) included in the study, 23 (21%) had early favorable HL, 14 (13%) had early unfavorable HL, and 71 (66%) had advanced-stage HL. The median CD4 count at HL diagnosis was 240/μL. The complete remission rates for patients with early favorable, early unfavorable, and advanced-stage HL were 96%, 100%, and 86%, respectively. The 2-year progression-free survival of the entire study population was 91.7%. Eleven patients (11%) have died, and treatment-related mortality was 5.6%. The 2-year overall survival rate was 90.7% with no significant difference between early favorable (95.7%), early unfavorable (100%), and advanced-stage HL (86.8%). Conclusion In patients with HIV-HL, stage- and risk-adapted treatment is feasible and effective. The prognosis for patients with HIV-HL may approach that of HIV-negative patients with HL.
Fetal and Neonatal Iron Deficiency Reduces Thyroid Hormone-Responsive Gene mRNA Levels in the Neonatal Rat Hippocampus and Cerebral Cortex
Authors: Bastian Thomas W. , Anderson Jeremy A. , Fretham Stephanie J. , Prohaska Joseph R. , Georgieff Michael K. , Anderson Grant W. 
Published: October 2012

Abstract
Copper (Cu), iron (Fe), and thyroid hormone (TH) deficiencies produce similar defects in late brain development including hypomyelination of axons and impaired synapse formation and function, suggesting that these micronutrient deficiencies share a common mechanism contributing to these derangements. We previously demonstrated that fetal/neonatal Cu and Fe deficiencies lower circulating TH concentrations in neonatal rats. Fe deficiency also reduces whole-brain T3 content, suggesting impaired TH action in the developing Fe-deficient brain. We hypothesized that fetal/neonatal Cu and Fe deficiencies will produce mild or moderate TH deficiencies and will impair TH-responsive gene expression in the neonatal cerebral cortex and hippocampus. To test this hypothesis, we rendered pregnant Sprague Dawley rats Cu-, Fe-, or TH-deficient from early gestation through postnatal d 10 (P10). Mild and moderate TH deficiencies were induced by 1 and 3 ppm propylthiouracil treatment, respectively. Cu deficiency did not significantly alter serum or tissue TH concentrations or TH-responsive brain mRNA expression. Fe deficiency significantly lowered P10 serum total T3 (45%), serum total T4 (52%), whole brain T3 (14%), and hippocampal T3 (18%) concentrations, producing a mild TH deficiency similar to 1 ppm propylthiouracil treatment. Fe deficiency lowered Pvalb, Enpp6, and Mbp mRNA levels in the P10 hippocampus. Fe deficiency also altered Hairless, Dbm, and Dio2 mRNA levels in the P10 cerebral cortex. These results suggest that some of the brain defects associated with Fe deficiency may be mediated through altered thyroidal status and the concomitant alterations in TH-responsive gene transcription.
Mixing Properties of Binary Liquid Mixtures of Cyclopentane with Branched Alcohols at Different Temperatures
Authors: Kumar Harsh , Chadha Chanda 
Published: October 2012

Abstract
Densities, ρ, and speeds of sound, u, of cyclopentane with 2-methyl-1-propanol, 3-methyl-1-butanol, and 2-methyl-2-butanol binary liquid mixtures have been measured over the whole composition range at atmospheric pressure at temperatures: 288.15, 298.15, and 308.15 K. Excess molar volumes VmE, isentropic compressibility κS, and their excess counterpart excess isentropic compressibility KS,mE have been calculated from experimental densities and speeds of sound. Apparent molar volume, Vφ,i partial molar volume, Vi, and apparent molar compressibilities have been calculated from the experimental density and speeds of measurements.
Effects of Piracy on Quality of Information Goods
Authors: Lahiri Atanu , Dey Debabrata 
Published: October 2012

It is commonly believed that piracy of information goods leads to lower profits, which translate to lower incentives to invest in innovation and eventually to lower-quality products. Manufacturers, policy makers, and researchers all claim that inadequate piracy enforcement efforts translate to lower investments in product development. However, we find many practical examples that contradict this claim. Therefore, to examine this claim more carefully, we develop a rigorous economic model of the manufacturer's quality decision problem in the presence of piracy. We consider a monopolist who does not have any marginal costs but has a product development cost quadratic in the quality level produced. The monopolist faces a consumer market heterogeneous in its preference for quality and offers a quality level that maximizes its profit. We also allow for the possibility that the manufacturer may use versioning to counter piracy. We unexpectedly find that in certain situations, lower piracy enforcement increases the monopolist's incentive to invest in quality. We explain the reasons and welfare implications of our findings. This paper was accepted by Lorin Hitt, information systems.
Industry or Academia, Basic or Applied? Career Choices and Earnings Trajectories of Scientists
Authors: Agarwal Rajshree , Ohyama Atsushi 
Published: October 2012

We extend life cycle models of human capital investments by incorporating matching theory to examine the sorting pattern of heterogeneous scientists into different career trajectories. We link differences in physical capital investments and complementarities between basic and applied scientists across industry and academic settings to individual differences in scientist ability and preferences to predict an equilibrium matching of scientists to careers and to their earnings evolution. Our empirical analysis, using the National Science Foundation's Scientists and Engineers Statistical Data System database, is consistent with theoretical predictions of (i) sorting by ability into basic versus applied science among academic scientists, but not among industry scientists; and (ii) sorting by higher taste for nonmonetary returns into academia over industry. The evolution of an earnings profile is consistent with these sorting patterns: the earnings trajectories of basic and applied scientists are distinct from each other in academia but are similar in industry. This paper was accepted by Lee Fleming, entrepreneurship and innovation.
Worst-Case Value at Risk of Nonlinear Portfolios
Authors: Zymler Steve , Kuhn Daniel , Rustem Berç 
Published: October 2012

Portfolio optimization problems involving value at risk (VaR) are often computationally intractable and require complete information about the return distribution of the portfolio constituents, which is rarely available in practice. These difficulties are compounded when the portfolio contains derivatives. We develop two tractable conservative approximations for the VaR of a derivative portfolio by evaluating the worst-case VaR over all return distributions of the derivative underliers with given first- and second-order moments. The derivative returns are modelled as convex piecewise linear or—by using a delta–gamma approximation—as (possibly nonconvex) quadratic functions of the returns of the derivative underliers. These models lead to new worst-case polyhedral VaR (WPVaR) and worst-case quadratic VaR (WQVaR) approximations, respectively. WPVaR serves as a VaR approximation for portfolios containing long positions in European options expiring at the end of the investment horizon, whereas WQVaR is suitable for portfolios containing long and/or short positions in European and/or exotic options expiring beyond the investment horizon. We prove that—unlike VaR that may discourage diversification—WPVaR and WQVaR are in fact coherent risk measures. We also reveal connections to robust portfolio optimization. This paper was accepted by Dimitris Bertsimas, optimization.
Reviews Books
Authors: Chatham Hugh , Hillier David , Labuza Peter , O’Reilly Erin 
Published: October 2012

Directory of World Cinema: American Independent, John Berra (ed.), (2010) Chicago: Intellect, 327pp., ISBN: 9781841503684 (pbk), $25.00
Film England: Culturally English Film-making since the 1990s, Andrew Higson, (2011) New York: I.B. Taurus, 296pp., ISBN: 9781848854536 (pbk),
$34.00
Steven Soderbergh, Aaron Baker, (2011) Chicago: University of Illinois press, 132pp., ISBN: 9780252077968 (pbk), $22.00
Hedy Lamarr: The Most Beautiful Woman in Film, Ruth Barton, (2010) Lexington: University Press of Kentucky, 281pp., ISBN: 9780813126043 (hbk),
$29.95
Exploration of the Genetic Organization of Morphological Modularity on the Mouse Mandible Using a Set of Interspecific Recombinant Congenic Strains Between C57BL/6 and Mice of theMus spretusSpecies
Authors: Burgio Gaëtan , Baylac Michel , Heyer Evelyne , Montagutelli Xavier 
Published: October 2012

AbstractMorphological integration and modularity within semi-autonomous modules are essential mechanisms for the evolution of morphological traits. However, the genetic makeup responsible for the control of variational modularity is still relatively unknown. In our study, we tested the hypothesis that the genetic variation for mandible shape clustered into two morphogenetic components: the alveolar group and the ascending ramus. We used the mouse as a model system to investigate genetics determinants of mandible shape. To do this, we used a combination of geometric morphometric tools and a set of 18 interspecific recombinant congenic strains (IRCS) derived from the distantly related species, Mus spretus SEG/Pas and Mus musculus C57BL/6. Quantitative trait loci (QTL) analysis comparing mandible morphometry between the C57BL/6 and the IRCSs identified 42 putative SEG/Pas segments responsible for the genetic variation. The magnitude of the QTL effects was dependent on the proportion of SEG/Pas genome inherited. Using a multivariate correlation coefficient adapted for modularity assessment and a two-block partial least squares analysis to explore the morphological integration, we found that these QTL clustered into two well-integrated morphogenetic groups, corresponding to the ascending ramus and the alveolar region. Together, these results provide evidence that the mouse mandible is subjected to genetic coordination in a modular manner.
Functional Analysis With a Barcoder Yeast Gene Overexpression System
Authors: Douglas Alison C , Smith Andrew M , Sharifpoor Sara , Yan Zhun , Durbic Tanja , Heisler Lawrence E , Lee Anna Y , Ryan Owen , Göttert Hendrikje , Surendra Anu , van Dyk Dewald , Giaever Guri , Boone Charles , Nislow Corey , Andrews Brenda J 
Published: October 2012

Abstract
Systematic analysis of gene overexpression phenotypes provides an insight into gene function, enzyme targets, and biological pathways. Here, we describe a novel functional genomics platform that enables a highly parallel and systematic assessment of overexpression phenotypes in pooled cultures. First, we constructed a genome-level collection of ~5100 yeast barcoder strains, each of which carries a unique barcode, enabling pooled fitness assays with a barcode microarray or sequencing readout. Second, we constructed a yeast open reading frame (ORF) galactose-induced overexpression array by generating a genome-wide set of yeast transformants, each of which carries an individual plasmid-born and sequence-verified ORF derived from the Saccharomyces cerevisiae full-length EXpression-ready (FLEX) collection. We combined these collections genetically using synthetic genetic array methodology, generating ~5100 strains, each of which is barcoded and overexpresses a specific ORF, a set we termed “barFLEX.” Additional synthetic genetic array allows the barFLEX collection to be moved into different genetic backgrounds. As a proof-of-principle, we describe the properties of the barFLEX overexpression collection and its application in synthetic dosage lethality studies under different environmental conditions.
Fractionation, Stability, and Isolate-Specificity of QTL for Resistance toPhytophthora infestansin Cultivated Tomato (Solanum lycopersicum)
Authors: Johnson Emily B , Haggard J Erron , St.Clair Dina A 
Published: October 2012

AbstractCultivated tomato (Solanum lycopersicum) is susceptible to late blight, a major disease caused by Phytophthora infestans, but quantitative resistance exists in the wild tomato species S. habrochaites. Previously, we mapped several quantitative trait loci (QTL) from S. habrochaites and then introgressed each individually into S. lycopersicum. Near-isogenic lines (NILs) were developed, each containing a single introgressed QTL on chromosome 5 or 11. NILs were used to create two recombinant sub-NIL populations, one for each target chromosome region, for higher-resolution mapping. The sub-NIL populations were evaluated for foliar and stem resistance to P. infestans in replicated field experiments over two years, and in replicated growth chamber experiments for resistance to three California isolates. Each of the original single QTL on chromosomes 5 and 11 fractionated into between two and six QTL for both foliar and stem resistance, indicating a complex genetic architecture. The majority of QTL from the field experiments were detected in multiple locations or years, and two of the seven QTL detected in growth chambers were co-located with QTL detected in field experiments, indicating stability of some QTL across environments. QTL that confer foliar and stem resistance frequently co-localized, suggesting that pleiotropy and/or tightly linked genes control the trait phenotypes. Other QTL exhibited isolate-specificity and QTL × environment interactions. Map-based comparisons between QTL mapped in this study and Solanaceae resistance genes/QTL detected in other published studies revealed multiple cases of co-location, suggesting conservation of gene function.
Multiple Pathways Regulate Minisatellite Stability During Stationary Phase in Yeast
Authors: Kelly Maire K , Brosnan Laura , Jauert Peter A , Dunham Maitreya J , Kirkpatrick David T 
Published: October 2012

AbstractAlterations in minisatellite DNA repeat tracts in humans have been correlated with a number of serious disorders, including cancer. Despite their importance for human health, the genetic factors that influence minisatellite stability are not well understood. Previously, we identified mutations in the Saccharomyces cerevisiae zinc homeostasis genes ZRT1 and ZAP1 that significantly increase the frequency of minisatellite alteration specifically during stationary phase. In this work, we identified mutants of END3, PKC1, and RAD27 that increase minisatellite instability during stationary phase. Genetic analysis reveals that these genes, along with ZRT1 and ZAP1, comprise multiple pathways regulating minisatellite stability during stationary phase. Minisatellite alterations generated by perturbation of any of these pathways occur via homologous recombination. We present evidence that suggests formation of ssDNA or ssDNA breaks may play a primary role in stationary phase instability. Finally, we examined the roles of these pathways in the stability of a human minisatellite tract associated with the HRAS1 oncogene and found that loss of RAD27, but not END3 or PKC1, destabilizes the HRAS1 minisatellite in stationary phase yeast. This result indicates that the genetic control of stationary phase minisatellite stability is dependent on the sequence composition of the minisatellite itself.