bluuebunny/crossref_metadata_2025_split huggingface dataset:
A fast universal solver for 1D continuous and discontinuous steady flows in rivers and pipes
Authors: Kerger François , Archambeau Pierre , Erpicum Sébastien , Dewals Benjamin J. , Pirotton Michel 
Published: December 2009

AbstractSimulation of 1D steady flow covers a wide range of practical applications, such as rivers, pipes and hydraulic structures. Various flow patterns coexist in such situations: free surface flows (supercritical, subcritical and hydraulic jump), pressurized flows as well as mixed flows. As a result, development of a unified 1D model for all the situations of interest in civil engineering remains challenging. In this paper, a fast universal solver for 1D continuous and discontinuous steady flows in rivers and pipes is set up and assessed. Developments are initiated from an original unified mathematical model using the Saint‐Venant equations. Application of these equations, originally dedicated to free‐surface flow, is extended to pressurized flow by means of the Preissmann slot model. In particular, an original negative slot is developed in order to handle sub‐atmospheric pressurized flow. Next, the full unsteady model is simplified under the assumption of steadiness and reformulated into a single pseudo‐unsteady differential equation. The derived pseudo‐unsteady formulation aims at keeping the hyperbolic feature of the equation. Stability analysis of the differential equation suggests a unique splitting for the finite volume scheme whatever the flow conditions. The numerical scheme obtained is a universal Flux Vector Splitting which shows robustness and simplicity. Accuracy and performance of the new methodology is assessed by comparison with analytical and experimental results. Copyright © 2009 John Wiley & Sons, Ltd.
Nowcasting from disaggregates in the face of location shifts
Authors: Castle Jennifer L. , Hendry David F. 
Published: December 2009

AbstractGiven a need for nowcasting, we consider how nowcasts can best be achieved, the use and timing of information, including disaggregation over variables and common features, and the role of automatic model selection for nowcasting missing disaggregates. We focus on the impact of location shifts on nowcast failure and nowcasting during breaks, using impulse saturation, its relation to intercept correction, and to robust methods to avoid systematic nowcast failure. We propose a nowcasting strategy, building models of all N disaggregate series by automatic methods, forecasting every variable each period, then testing for shifts in available measures, switching to robust forecasts of missing series when breaks are detected. Copyright © 2009 John Wiley & Sons, Ltd.
The UK intranational business cycle
Authors: Artis Michael , Okubo Toshihiro 
Published: December 2009

AbstractThe paper uses annual data on real GDP for 12 UK regions and 12 manufacturing sectors to derive regional and regional/sectoral business cycles using a Hodrick–Prescott filter. The cohesion of the cycles is examined via cross‐correlations and comparisons made with the regional cycles for Japan, the USA and the euro area. The UK emerges as especially cohesive and efforts to explain the overall cross‐correlations of regional GDP are not very successful owing to the low variance of the explicand; when attention is turned to the sectoral/regional cycles, with their greater variance, it is possible to demonstrate that economic variables such as distance, dissimilarity in structure and level of output play a significant role in explaining the variance in the cross‐correlations. A significant feature of the cross‐correlations in relation to those of EU countries is that while they continue to provide support for the ‘UK idiosyncrasy’ they no longer do so as strongly as they did in earlier data samples. Copyright © 2009 John Wiley & Sons, Ltd.
Estimation of genotype relative risks from pedigree data by retrospective likelihoods
Authors: Schaid Daniel J. , McDonnell Shannon K. , Riska Shaun M. , Carlson Erin E. , Thibodeau Stephen N. 
Published: December 2009

AbstractPedigrees collected for linkage studies are a valuable resource that could be used to estimate genetic relative risks (RRs) for genetic variants recently discovered in case‐control genome wide association studies. To estimate RRs from highly ascertained pedigrees, a pedigree “retrospective likelihood” can be used, which adjusts for ascertainment by conditioning on the phenotypes of pedigree members. We explore a variety of approaches to compute the retrospective likelihood, and illustrate a Newton‐Raphson method that is computationally efficient particularly for single nucleotide polymorphisms (SNPs) modeled as log‐additive effect of alleles on the RR. We also illustrate, by simulations, that a naïve “composite likelihood” method that can lead to biased RR estimates, mainly by not conditioning on the ascertainment process—or as we propose—the disease status of all pedigree members. Applications of the retrospective likelihood to pedigrees collected for a prostate cancer linkage study and recently reported risk‐SNPs illustrate the utility of our methods, with results showing that the RRs estimated from the highly ascertained pedigrees are consistent with odds ratios estimated in case‐control studies. We also evaluate the potential impact of residual correlations of disease risk among family members due to shared unmeasured risk factors (genetic or environmental) by allowing for a random baseline risk parameter. When modeling only the affected family members in our data, there was little evidence for heterogeneity in baseline risks across families. Genet. Epidemiol. 34: 287–298, 2010. © 2009 Wiley‐Liss, Inc.
Case‐only gene‐environment interaction studies: when does association imply mechanistic interaction?
Authors: VanderWeele Tyler J. , Hernández‐Díaz Sonia , Hernán Miguel A. 
Published: December 2009

AbstractCase‐only studies are often used to identify interactions between a genetic factor and an environmental factor under the assumption both factors are independent in the population. However, interpreting a statistical association between the genetic and the environmental factors among the cases, as evidence of a mechanistic gene‐environment interaction, is not always warranted. Using a mechanistic approach based on the sufficient cause framework, we show association amongst cases can arise between the genetic and environmental factors when there is in fact no mechanistic gene‐environment interaction. However, when it can be assumed the genetic and environmental factors themselves can never prevent the outcome, we show a positive association amongst cases implies a mechanistic gene‐environment interaction. Without this assumption that the effects of the two factors are never preventive, a multiplicative interaction greater than two is needed to conclude the presence of a mechanistic interaction. We furthermore show these tests for mechanistic interaction can be extended to scenarios in which the genetic and environmental factors are negatively associated in the population rather than independent. Genet. Epidemiol. 34: 327–334, 2010. © 2009 Wiley‐Liss, Inc.
A powerful approach to sub‐phenotype analysis in population‐based genetic association studies
Authors: Morris Andrew P. , Lindgren Cecilia M. , Zeggini Eleftheria , Timpson Nicholas J. , Frayling Timothy M. , Hattersley Andrew T. , McCarthy Mark I. 
Published: December 2009

AbstractThe ultimate goal of genome‐wide association (GWA) studies is to identify genetic variants contributing effects to complex phenotypes in order to improve our understanding of the biological architecture underlying the trait. One approach to allow us to meet this challenge is to consider more refined sub‐phenotypes of disease, defined by pattern of symptoms, for example, which may be physiologically distinct, and thus may have different underlying genetic causes. The disadvantage of sub‐phenotype analysis is that large disease cohorts are sub‐divided into smaller case categories, thus reducing power to detect association. To address this issue, we have developed a novel test of association within a multinomial regression modeling framework, allowing for heterogeneity of genetic effects between sub‐phenotypes. The modeling framework is extremely flexible, and can be generalized to any number of distinct sub‐phenotypes. Simulations demonstrate the power of the multinomial regression‐based analysis over existing methods when genetic effects differ between sub‐phenotypes, with minimal loss of power when these effects are homogenous for the unified phenotype. Application of the multinomial regression analysis to a genome‐wide association study of type 2 diabetes, with cases categorized according to body mass index, highlights previously recognized differential mechanisms underlying obese and non‐obese forms of the disease, and provides evidence of a potential novel association that warrants follow‐up in independent replication cohorts. Genet. Epidemiol. 34: 335–343, 2010.  © 2009 Wiley‐Liss, Inc.
Alterations in cortical activity of male methamphetamine abusers performing an empathy task: fMRI study
Authors: Kim Yang‐Tae , Lee Jae‐Jun , Song Hui‐Jin , Kim Joo‐Hyun , Kwon Do‐Hoon , Kim Myoung‐Nam , Yoo Done‐Sik , Lee Hui Joong , Kim Hye‐Jung , Chang Yongmin 
Published: December 2009

AbstractObjectivesWe investigate possible differences in neural correlates of empathy processing between abstinent methamphetamine (MA) abusers and healthy subjects using functional magnetic resonance imaging (fMRI).MethodsNineteen abstinent MA abusers (mean age of 36.06 years, range 31–52 years) and 19 healthy subjects (mean age of 37.05 years, range 33–42 years) participated in this study. A visual fMRI activation paradigm was used, comprising a series of cartoons, each depicting a short story. There were two categories of stories: empathy (Empathy) and Physical causality (Physical). fMRI images were acquired using a 3.0 T whole‐body scanner. All fMRI data were analyzed using MATLAB v. 7.2 and SPM5.ResultsBoth MA subjects and controls exhibited activation in the dorsomedial prefrontal cortex. Despite this similarity in activation patterns, we found that the two groups differed in the activation of several cortical regions associated with the processing of empathy information. Hypoactivations of the orbitofrontal cortex, temporal poles, and hippocampus in MA abusers relative to healthy subjects suggests that the ability of empathic response could be compromised in abstinent MA abusers (p < 0.05, corrected for a small volume).ConclusionsFunctional impairments in the empathic neural network caused by MA may contribute to the misunderstanding of others and to the erosion of social interactions in MA abusers. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of metabolic blockade on the psychoactive effects of dextromethorphan
Authors: Zawertailo Laurie A. , Tyndale Rachel F. , Busto U. , Sellers Edward M. 
Published: December 2009

AbstractObjectiveVariation in the activity of cytochrome P450 2D6 (CYP2D6) affects the pharmacokinetics and effectiveness of dextromethorphan (DM), because it controls the production of dextrorphan, an active metabolite, with higher affinity for the NMDA receptor than the parent compound. This study examined whether pharmacological inhibition of CYP2D6 activity with quinidine would mimic the genetic mutation and thus also alter the psychoactive effects of DM.MethodsIn a single‐blind, within‐subjects study, eight healthy volunteers (all homozygous for the wild type allele for CYP2D6) received placebo and varying doses of DM, both with and without quinidine pre‐treatment. Pharmacokinetic and pharmacodynamic measures were assessed at baseline and every hour post‐drug for 6 h.ResultsCompared to the no quinidine condition, quinidine pre‐treatment decreased the area under the dose–response curve on subjective measures of positively reinforcing effects (e.g., euphoria,p < 0.04; drug liking,p < 0.05), and was significantly greater for measures of dysphoria (e.g., unpleasantness,p < 0.02). These changes corresponded to increased DM and decreased dextrorphan plasma concentrations.ConclusionsCompared to DM alone, quinidine pre‐treatment inhibited DM metabolism and changed its subjective effects, demonstrating that the psychoactive properties of DM are a function of drug metabolism. These results demonstrate the relationship between CYP2D6 activity, plasma drug levels, and psychoactive drug effects, and have implications for both the abuse liability and therapeutic utility of DM. Copyright © 2009 John Wiley & Sons, Ltd.
Missense polymorphisms in three oxidative‐stress enzymes (GSTP1, SOD2, and GPX1) and dyskinesias in Russian psychiatric inpatients from Siberia
Authors: Al Hadithy A. F. Y. , Ivanova S. A. , Pechlivanoglou P. , Wilffert B. , Semke A. , Fedorenko O. , Kornetova E. , Ryadovaya L. , Brouwers J. R. B. J. , Loonen A. J. M. 
Published: December 2009

AbstractNeuronal degeneration due to oxidative stress (OS) has been proposed as a mechanism for tardive dyskinesia (TD) pathogenesis. Cellular defense mechanisms against OS may involve detoxification enzymes (e.g., glutathione peroxidase‐1, GPX1; superoxide dismutase‐2, SOD2 [also commonly known as MnSOD]; and glutathione S‐transferase P1, GSTP1). Several pharmacogenetic studies have examined TD and OS in different ethnic groups, but not in Russians. Here we report the association between orofaciolingual (TDof) and limb‐truncal dyskinesias (TDlt) and polymorphisms of GSTP1 (Ile105Val), MnSOD (Ala‐9Val), and GPX1 (Pro197Leu) genes in 146 Russian inpatients from Siberia. We applied AIMS instrument to rate dyskinesias. Two‐part model analyses, logistic and multivariate parametric regressions were applied to assess the effects of different variables (e.g., genotype, age, gender, and medication use). Our analyses do not suggest that Pro197Leu (GPX1) is associated with TD. However, our analyses suggest that the 105Val‐allele of Ile105Val (GSTP1) may be associated with a lower risk and a severity of TDof and TDlt and that Ile105Val pharmacogenetics may be different in Slavonic Caucasians from that in American Caucasians. Furthermore, we find evidence for an association between Ala‐9Val (MnSOD) and TDof, but not TDlt. Subject to further replication, our findings extend the available knowledge on the pharmacogenetics of TD and oxidative stress. Copyright © 2009 John Wiley & Sons, Ltd.
Analysis of anti‐proliferative and chemosensitizing effects of sunitinib on human esophagogastric cancer cells: Synergistic interaction with vandetanib via inhibition of multi‐receptor tyrosine kinase pathways
Authors: Lyros Orestis , Mueller Annett , Heidel Florian , Schimanski Carl C. , Gockel Ines , Galle Peter R. , Lang Hauke , Moehler Markus 
Published: December 2009

AbstractThe receptor tyrosine kinases (RTKs), epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 1‐3 (VEGFR1‐3), are frequently expressed in gastric cancer and are putative therapeutic targets in this disease. We have investigated the anti‐proliferative and chemosensitizing properties of the multitargeted small‐molecule RTK inhibitors sunitinib and vandetanib in a panel of 4 human gastric and esophageal cancer cell lines. In the 1st instance, the expression of potential targets of these small‐molecule inhibitors was examined by reverse transcriptase‐polymerase chain reaction, western blotting, and flow cytometry. EGFR mRNA and protein was detected in all cases, with VEGFR2 expression noted in all but 1 line. Both EGF and VEGF were shown to stimulate tumor cell growth, and both sunitinib and vandetanib were found to be associated with significant dose‐dependent inhibition of proliferation and an enhancement of apoptosis, as determined by MTT and propidium iodide/Annexin V labeling assays, respectively. The addition of sunitinib to VEGF‐stimulated NCI‐N87 cells was associated with a reduction in MAPK phosphorylation (pMAPK) but not Akt phosphorylation (pAkt), whereas the addition of vandetanib was associated with reductions in both VEGF‐ and EGF‐mediated VEGFR2 phosphorylation, pMAPK and pAkt. Co‐administration of sunitinib significantly enhanced the sensitivity of MKN‐45 cells to cisplatin and irinotecan. In addition, vandetanib synergistically enhanced the sunitinib‐associated inhibition of gastric cancer cell growth. In conclusion, these preliminary data confirm the importance of EGFR and VEGFR signaling in gastric cancer and suggest that the simultaneous inhibition of RTK‐pathways through sunitinib and vandetanib may provide therapeutic benefit in this disease.
Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in the E3N‐EPIC study
Authors: Maillard Virginie , Kuriki Kiyonori , Lefebvre Benoît , Boutron‐Ruault Marie‐Christine , Lenoir Gilbert M. , Joulin Virginie , Clavel‐Chapelon Françoise , Chajès Véronique 
Published: December 2009

AbstractEvidence of a protective effect of fruit and vegetable intake on breast cancer risk is inconsistent. Epidemiologic cohort studies based on blood carotenoid intakes as biomarkers of consumption of fruits and vegetable in individuals are still scare and findings are discrepant. The study population included women in the E3N Study, the large French component of the European Prospective Investigation into Cancer and Nutrition (EPIC). During an average of 7 years follow‐up, 366 cases of incident invasive breast cancer (84 premenopausal women and 282 postmenopausal women) among 19,934 women who completed a dietary questionnaire and had available blood samples at baseline (1995–1998) were included in the study. Controls were randomly matched on age, menopausal status at blood collection, fasting status at blood collection, date and collection center. Serum carotenoids, tocopherols and retinol concentrations were assessed by high pressure liquid chromatography. Odds ratios for breast cancer risk adjusted for established breast cancer risk factors were calculated by quintile of serum micronutrient concentrations. No significant associations between breast cancer risk and serum carotenoids (highest versus lowest quintile, odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.47–1.16, p for trend 0.38), tocopherols (OR = 0.68, 95% CI = 0.41–1.10, p for trend 0.26) and retinol (OR = 0.85, 95% CI = 0.53–1.35, p for trend 0.34) were found. Our findings did not support the hypothesis that lipophilic antioxidant micronutrients found in fruits and vegetables protect against breast cancer, at least in postmenopausal women.
Association between antibiotic use and risk of prostate cancer
Authors: Tamim Hani M. , Hajeer Ali H. , Boivin Jean‐François , Collet Jean‐Paul 
Published: December 2009

AbstractThe association between antibiotics and risk of cancer has been addressed in different studies, most of which were addressing breast cancer. The objective of this study was to assess the association between antibiotics use and risk of prostate cancer. We carried out a population‐based case‐control study using data from Saskatchewan Health administrative databases (Canada) between the years 1981 and 2000. Cases identified by the Saskatchewan Cancer Agency were matched to 4 controls, using incidence density sampling. The effect of dosage and timing of antibiotic use, over a minimum of 15 years before diagnosis, on prostate cancer risk was assessed. Number of prescriptions and number of tablets were used as exposure definitions. Moreover, the effect of different classes of antibiotics on prostate cancer was also studied. A total of 4,052 prostate cancer cases and 16,208 matched controls were included in this study. Antibiotics exposure (number of prescriptions) during the period of 1–15 years in the past was significantly associated with an increased risk of prostate cancer; RR = 1.69, 2.61, 2.71, and 2.83 for the 4 quartiles, respectively, p‐trend = 0.0001. When number of units was taken as the exposure definition, similar results were found. We did not find any effect of the timing or class of antibiotic exposure on prostate cancer risk. We found a dose‐dependent association between antibiotics exposure up to 15 years in the past and risk of prostate cancer. However, the lack of temporal trends and the absence of class specific effects suggest a noncausal relationship.
Transient depletion of CD4+ T cells augments IL‐21‐based immunotherapy of disseminated neuroblastoma in syngeneic mice
Authors: Croce Michela , Corrias Maria Valeria , Orengo Anna Maria , Brizzolara Antonella , Carlini Barbara , Borghi Martina , Rigo Valentina , Pistoia Vito , Ferrini Silvano 
Published: December 2009

AbstractIL‐21 is a member of the IL‐2 cytokine family, produced by CD4+ T cells. We previously showed that immunotherapy (IT) with IL‐21‐transduced neuroblastoma cells (Neuro2a/IL‐21) cured 33% of syngeneic mice bearing systemic NB. Here, we studied whether the removal of Treg cells could potentiate the therapeutic efficacy of Neuro2a/IL‐21 vaccine. The administration of anti‐CD25 mAb, which targets Treg cells, slightly potentiated the effect of vaccine IT (50% cure rate), but anti‐CD4 mAb had a more potent effect leading to 80% cure rate. Anti‐CD25 mAb, indeed, only partially depleted CD4+CD25+FoxP3+ Treg cells, whereas anti‐CD4 mAb was more effective in this respect, leading to 90% depletion of Treg cells. In mice receiving vaccine+anti‐CD4 mAb, which developed systemic immunity to NB, CD4+ T cells counts completely recovered in 90 days. Depletion of CD8+ T cells abrogated the effect of the combined IT, indicating a predominant role of these cells in driving the immune response. In addition, CD8+ T cells from cured mice coinjected with Neuro2a/parental cells (pc) in NOD‐SCID mice completely inhibited tumor growth. Spleen cells from mice receiving Neuro2a/IL‐21 vaccination showed increased expression of IFN‐alpha2, ‐beta1 and ‐gamma mRNA. Moreover, mice receiving vaccine therapy alone or vaccine+anti‐CD4 mAb showed increased IFN‐gamma serum levels and IFN‐gamma‐producing CD8+ T cells were found in spleen cells. In conclusion, anti‐CD4 mAb potentiated IL‐21‐based IT by removing Treg cells and/or their precursors and other potentially immune‐suppressive CD4+ cell subsets, thus allowing the development of an IL‐21‐driven CD8+ T cell response, which mediates NB rejection.
Detoxification of aristolochic acid I by O‐demethylation: Less nephrotoxicity and genotoxicity of aristolochic acid Ia in rodents
Authors: Shibutani Shinya , Bonala Radha R. , Rosenquist Thomas , Rieger Robert , Suzuki Naomi , Johnson Francis , Miller Frederick , Grollman Arthur P. 
Published: December 2009

AbstractIngestion of aristolochic acids (AA) contained in herbal remedies results in aristolochic acid nephropathy (AAN), which is characterized by chronic renal failure, tubulointerstitial fibrosis and urothelial cancer. AA I and AA II, primary components in AA, have similar genotoxic potential, whereas only AA I shows severe renal toxicity in rodents. AA I is demethylated to form 8‐hydroxy‐aristolochic acid I (AA Ia) as a major metabolite. However, the nephrotoxicity and genotoxicity of AA Ia has not yet been determined. AA Ia was isolated from urine collected from rats treated with AA I and characterized by NMR and mass spectrometry. The purified AA Ia was administered intraperitoneally to C3H/He male mice for 9 days and its toxicity was compared with AA I. Using 32P‐postlabeling/polyacrylamide gel electrophoresis, the level of AA Ia‐derived DNA adducts in renal cortex was ∼70–110 times lower than that observed with AA I, indicating that AA Ia has only a limited genotoxicity. Supporting this result, when calf thymus DNA was reacted with AA Ia in a buffer containing zinc dust, the formation of AA Ia‐DNA adducts was two‐orders of magnitude lower than that of AA I. Histopathologic analysis revealed that unlike AA I, no significant changes were detected in the renal cortex of mice treated with AA Ia. Therefore, the contribution of AA Ia to renal toxicity is minimum. We conclude the metabolic pathway of converting AA I to AA Ia functions as the detoxification of AA I.