bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Redox Enzyme p66Shc Contributes to Diabetes and Ischemia-Induced Delay in Cutaneous Wound Healing
Authors: Fadini Gian Paolo , Albiero Mattia , Menegazzo Lisa , Boscaro Elisa , Pagnin Elisa , Iori Elisabetta , Cosma Chiara , Lapolla Annunziata , Pengo Vittorio , Stendardo Massimo , Agostini Carlo , Pelicci Pier Giuseppe , Giorgio Marco , Avogaro Angelo 
Published: June 2010

OBJECTIVE
The redox enzyme p66Shc produces hydrogen peroxide and triggers proapoptotic signals. Genetic deletion of p66Shc prolongs life span and protects against oxidative stress. In the present study, we evaluated the role of p66Shc in an animal model of diabetic wound healing.

RESEARCH DESIGN AND METHODS
Skin wounds were created in wild-type (WT) and p66Shc−/− control and streptozotocin-induced diabetic mice with or without hind limb ischemia. Wounds were assessed for collagen content, thickness and vascularity of granulation tissue, apoptosis, reepithelialization, and expression of c-myc and β-catenin. Response to hind limb ischemia was also evaluated.

RESULTS
Diabetes delayed wound healing in WT mice with reduced granulation tissue thickness and vascularity, increased apoptosis, epithelial expression of c-myc, and nuclear localization of β-catenin. These nonhealing features were worsened by hind limb ischemia. Diabetes induced p66Shc expression and activation; wound healing was significantly faster in p66Shc−/− than in WT diabetic mice, with or without hind limb ischemia, at 1 and 3 months of diabetes duration and in both SV129 and C57BL/6 genetic backgrounds. Deletion of p66Shc reversed nonhealing features, with increased collagen content and granulation tissue thickness, and reduced apoptosis and expression of c-myc and β-catenin. p66Shc deletion improved response to hind limb ischemia in diabetic mice in terms of tissue damage, capillary density, and perfusion. Migration of p66Shc−/− dermal fibroblasts in vitro was significantly faster than WT fibroblasts under both high glucose and hypoxia.

CONCLUSIONS
p66Shc is involved in the delayed wound-healing process in the setting of diabetes and ischemia. Thus, p66Shc may represent a potential therapeutic target against this disabling diabetes complication.
Pragmatics in pre‐schoolers with language impairments
Authors: Geurts Hilde , Embrechts Mariëtte 
Published: June 2010

Background: Pragmatic assessment methods are very diverse and differ in informant type. Some rely on parents, others on teachers/professionals and some directly test pragmatic abilities in the children themselves. A widely used pragmatic parent questionnaire is the Children's Communication Checklist—2 (CCC‐2). However, it is not known how scores on the CCC‐2 relate to direct measures of pragmatics.Aims: The aim of the current study is determine whether children's language patterns on pragmatics obtained with a parent questionnaire were converging with findings when the children were directly tested with a pragmatic test.Methods & Procedures: The CCC‐2 and the Nijmegen Pragmatics Test (NPT) were applied to 24 pre‐schoolers (aged 4–7 years) with various language impairments and 33 age‐matched typically developing pre‐schoolers.Outcomes & Results: Both pragmatic language instruments clearly differentiated between pre‐schoolers with language impairments and those without language impairments. However, the obtained correlations between the different measures were low to moderate. The specificity of each of the instruments was sufficient, but the sensitivity was generally poor.Conclusions & Implications: The instruments were not always converging, but when the instruments did converge the obtained results were valid. However, the obtained high specificity and relatively low sensitivity values for each of the instruments showed that better cut‐off scores are needed. When only one of the instruments indicated the absence or presence of language impairments, one needs to be careful in concluding whether or not there are indeed language impairments.
Role of phonotactic frequency in nonword repetition by children with specific language impairments
Authors: Coady Jeffry , Evans Julia L. , Kluender Keith R. 
Published: June 2010

Background: Children with specific language impairments (SLI) repeat nonwords less accurately than typically developing children, suggesting a phonological deficit. Much work has attempted to explain these results in terms of a phonological memory deficit. However, subsequent work revealed that these results might be explained better as a deficit in phonological sensitivity.Aims: This study used a nonword repetition task to examine how children with SLI extract phonological regularities from their language input.Methods & Procedures: Eighteen English‐speaking children with SLI (7;3–10;6) and 18 age‐matched controls participated in two English nonword repetition tasks. Three‐ and four‐syllable nonwords varied in a single phonotactic frequency manipulation, either consonant frequency or phoneme co‐occurrence frequency, while all other factors were held constant. Repetitions were scored in terms of accuracy as either the percentage of phonemes correctly produced or phoneme co‐occurrences (diphones) correctly produced. In addition, onset‐to‐onset reaction times and repetition durations were measured.Outcomes & Results: Accuracy results revealed significant group, length, and phonotactic frequency effects. Children with SLI repeated nonwords less accurately than age‐matched peers, and all children repeated three‐syllable nonwords and those with higher frequency phonotactic patterns more accurately. However, phonotactic frequency by group interactions were not significant. Timing results were mixed, with group reaction time differences for co‐occurrence frequency, but not consonant frequency, and no group repetition duration differences.Conclusions & Implications: While children with SLI were less accurate overall, non‐significant interactions indicate that both groups of children were comparably affected by differences in consonant and diphone frequency.
Estimated average annual rate of change of CD4+ T-cell counts in patients on combination antiretroviral therapy
Authors:   the EuroSIDA Study Group, Mocroft Amanda , Phillips Andrew N , Ledergerber Bruno , Smith Colette , Bogner Johannes R , Lacombe Karine , Wiercinska-Drapalo Alicje , Reiss Peter , Kirk Ole , Lundgren Jens D 
Published: June 2010

Background Patients receiving combination antiretroviral therapy (cART) might continue treatment with a virologically failing regimen. We sought to identify annual change in CD4+ T-cell count according to levels of viraemia in patients on cART. Methods A total of 111,371 CD4+ T-cell counts and viral load measurements in 8,227 patients were analysed. Annual change in CD4+ T-cell numbers was estimated using mixed models. Results After adjustment, the estimated average annual change in CD4+ T-cell count significantly increased when viral load was <500 copies/ml (30.4 cells/mm3, 95% confidence interval [CI] 26.6–34.3), was stable when viral load was 500–9,999 copies/ml (3.1 cells/mm3, 95% CI -5.3–11.5) and decreased when viral load was ≥10,000 copies/ml (-14.8 cells/mm3, 95% CI -4.5– - 25.1). Patients taking a boosted protease inhibitor (PI) regimen had more positive annual CD4+ T-cell count changes than patients taking other regimens for any given viral load strata: 30.9 cells/mm3 (95% CI 27.7–34.1) when viral load was <500 copies/ml, 14.2 cells/mm3 (95% CI -2.1–30.4) when viral load was 500–9,999 copies/ml and -19.9 cells/mm3 (95% CI -36.6– -3.3) when viral load was ≥10,000 copies/ml. By contrast, among patients taking a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimen, the CD4+ T-cell count significantly decreased when the viral load was 500–9,999 copies/ml (-18.6 cells/mm3, 95% CI -33.8– - 3.5) and decreased at a faster rate when the viral load was ≥10,000 copies/ml (-44.4 cells/mm3, 95% CI -62.0– -26.9; P=0.0012, test for interaction). Conclusions On average, CD4+ T-cell counts did not significantly decrease until the viral load exceeded 10,000 copies/ml in patients treated with a boosted PI-containing cART regimen, but decreased in patients taking an NNRTI-based cART regimen when viral load was 500–9,999 copies/ml.
Pyrimidine deoxynucleoside and nucleoside reverse transcriptase inhibitor metabolism in the perfused heart and isolated mitochondria
Authors: Morris Gerald W , LaClair Darcy D , McKee Edward E 
Published: June 2010

BackgroundThe metabolism of pyrimidine deoxynucleosides and nucleoside reverse transcriptase inhibitors has been studied in growing cells. However, many of these drugs are associated with mitochondrial toxicities observed in non-replicating tissues, such as in the heart, where their metabolism has not been investigated.MethodsThe aims of this study were twofold. The first was to investigate the metabolism of the thymidine analogues 3’-azido-3'deoxythymidine (AZT) and 2’,3’-didehydrodideoxy-thymidine (d4T), and the deoxycytidine (dCyd) analogues 2’-deoxy-3’-thiacytidine (3TC) and 2’,3’-dideoxycytidine (ddC) with regard to phosphorylation and breakdown. The second was to investigate their potential effects, singly or in combination with AZT, on metabolism of the naturally occurring deoxynucleosides in the perfused rat heart and in isolated heart mitochondria.ResultsThe analogue d4T was not metabolized in perfused heart or in isolated mitochondria, and had no effect on either thymidine or dCyd metabolism. The dCyd analogues were both phosphorylated in perfused heart to the triphosphate, but only at the limit of detection and they were not phosphorylated in isolated mitochondria. Neither ddC nor 3TC had any effect on thymidine or dCyd metabolism in either perfused heart or in isolated mitochondria. AZT has been previously shown to inhibit thymidine phosphorylation. When d4T, 3TC or ddC were given with AZT, only ddC caused a significant further decrease in thymidine phosphorylation.ConclusionsThese results indicate that with the exception of the competition between AZT and thymidine, there was little competition for phosphorylation among and between these other nucleoside reverse transcriptase inhibitors and the naturally occurring deoxynucleosides in cardiac tissue and isolated heart mitochondria.
Biomarkers of Liver Injury for Hepatitis Clinical Trials: A Meta-Analysis of Longitudinal Studies
Authors: Poynard Thierry , Ngo Yen , Munteanu Mona , Thabut Dominique , Massard Julien , Moussalli Joseph , Varaud Anne , Benhamou Yves , Ratziu Vlad 
Published: June 2010

BackgroundLiver biopsy and virological end points are standard references for assessing the effect of viral hepatitis treatments. We aimed to review evidence-based published data of biomarkers that have been validated as non-invasive alternatives to biopsy as end points for HBV and HCV infection trials.MethodsStudies were included if there were at least two repeated estimates of fibrosis per patient using biomarkers with at least two studies and a control group. Meta-analysis of the percentage of fibrosis progression per year (pFPy) was performed.ResultsTwo biomarkers were included, FibroTest® and liver stiffness measurement (LSM; FibroScan®). A total of 1,413 patients with chronic hepatitis C (11 populations) and 772 with chronic hepatitis B (6 populations) were analysed. In a comparison of HCV patients with controls, the FibroTest® pFPy was -18% (95% confidence interval [CI] -23– -14; P<0.001) in treated patients and the LSM pFPy was -15% (95% CI -28– -1; P=0.01), both with differences according to virological responses. In HBV patients, there was a significant decrease of the pFPy only in patients with baseline advanced fibrosis (mean difference -5% [95% CI -10– -0.1]; P=0.02). In patients with advanced fibrosis, stratified by virological response, there were similar differences between pFPy estimated either using FibroTest® or biopsy, both in HCV and HBV infections. Repeated LSM in HBV patients had an early variability related to necroinflammatory activity.ConclusionsIn patients with chronic hepatitis C and B, the treatment effect on fibrosis progression rate was similarly estimated using FibroTest® or biopsy. The same concordance was observed for FibroScan® but with a possible overestimation of the fibrosis regression during the first weeks of treatment.
Anthropometry in the prediction of sleep disordered breathing in HIV-positive and HIV-negative men
Authors: Brown Todd T , Patil Susheel P , Jacobson Lisa P , Margolick Joseph B , Laffan Alison M , Godfrey Rebecca J , Johnson Jacquett R , Johnson-Hill Lisette M , Reynolds Sandra M , Schwartz Alan R , Smith Philip L 
Published: June 2010

Background Body mass index (BMI), waist circumference (WC) and neck circumference (NC) are important screening tools for sleep disordered breathing (SDB); however, the utility of anthropometry for this purpose has not been evaluated among HIV-positive patients. Methods HIV-negative men ( n=60), HIV-positive men receiving highly active antiretroviral therapy (HIV- positive/ HAART; n=58) and HIV-positive men not receiving HAART (HIV-positive/no HAART; n=41) from the Multicenter AIDS Cohort Study underwent a nocturnal sleep study and anthropomorphic assessment. Moderate-severe SDB was defined as an apnea/hypopnea event rate ≥15 episodes/h. Receiver operating characteristic (ROC) curves were used to compare the ability of different anthropometric measurements to predict SDB within each group. Results Moderate-severe SDB was found in 48% of men (HIV-negative [57%], HIV-positive/HAART [41%] and HIV-positive/no HAART [44%]). The performance of BMI, WC and NC to predict SDB was excellent among the HIV-negative men (ROC areas under the curve [AUCs] 0.83, 0.88 and 0.88, respectively) and fair among the HIV-positive/HAART group (AUC 0.71, 0.77 and 0.77, respectively). By contrast, these measurements had no predictive value in the HIV-positive/no HAART group (AUC 0.43, 0.41 and 0.45, respectively). Moreover, in the HIV-positive/no HAART group, moderate-severe SDB was independently associated with serum C- reactive protein ≥3.0 mg/l (odds ratio 6.9; P=0.04) and HIV RNA>10,000 copies/ml (odds ratio 7.1; P=0.05). Conclusions BMI, WC and NC had a better predictive value for moderate-severe SDB in HIV-positive men compared with HIV-negative men, and had no value among HIV-positive/no HAART men. Among this latter group, systemic inflammation might contribute to the pathogenesis of SDB.
Flagellin Stimulates Protective Lung Mucosal Immunity: Role of Cathelicidin-Related Antimicrobial Peptide
Authors: Yu Fu-shin , Cornicelli Matthew D. , Kovach Melissa A. , Newstead Michael W. , Zeng Xianying , Kumar Ashok , Gao Nan , Yoon Sang Gi , Gallo Richard L. , Standiford Theodore J. 
Published: June 2010

Abstract
TLRs are required for generation of protective lung mucosal immune responses against microbial pathogens. In this study, we evaluated the effect of the TLR5 ligand flagellin on stimulation of antibacterial mucosal immunity in a lethal murine Pseudomonas aeruginosa pneumonia model. The intranasal pretreatment of mice with purified P. aeruginosa flagellin induced strong protection against intratracheal P. aeruginosa-induced lethality, which was attributable to markedly improved bacterial clearance, reduced dissemination, and decreased alveolar permeability. The protective effects of flagellin on survival required TLR5 and were observed even in the absence of neutrophils. Flagellin induced strong induction of innate genes, most notably the antimicrobial peptide cathelicidin-related antimicrobial peptide. Finally, flagellin-induced protection was partially abrogated in cathelicidin-related antimicrobial peptide-deficient mice. Our findings illustrate the profound stimulatory effect of flagellin on lung mucosal innate immunity, a response that might be exploited therapeutically to prevent the development of Gram-negative bacterial infection of the respiratory tract.
Moments of the Critical Values of Families of Elliptic Curves, with Applications
Authors: Young Matthew P. 
Published: June 2010

AbstractWe make conjectures on the moments of the central values of the family of all elliptic curves and on themoments of the first derivative of the central values of a large family of positive rank curves. In both cases the order of magnitude is the same as that of the moments of the central values of an orthogonal family of L-functions. Notably, we predict that the critical values of all rank 1 elliptic curves is logarithmically larger than the rank 1 curves in the positive rank family.Furthermore, as arithmetical applications, we make a conjecture on the distribution of ap's amongst all rank 2 elliptic curves and show how the Riemann hypothesis can be deduced from sufficient knowledge of the first moment of the positive rank family (based on an idea of Iwaniec).
On Some Explicit Constructions of Finsler Metrics with Scalar
Flag Curvature
Authors: Mo Xiaohuan , Yu Changtao 
Published: June 2010

AbstractWe give an explicit construction of polynomial (of arbitrary
degree) (α, β)-metrics with
scalar flag curvature and determine their scalar flag curvature. These
Finsler metrics contain all nontrivial projectively flat
(α, β)-metrics of constant flag
curvature.
La mesure dans l'enseignement des sciences physiques. Évolution au cours du temps
Authors: Séré Marie-Geneviève 
Published: June 2010

Au lycée, en travaux pratiques de physique et de chimie, les élèves apprennent le mesurage. Cependant, les pratiques ainsi que les objectifs des enseignants en la matière ont fortement évolué au cours des années. Cet article se propose de retracer l’évolution de l’enseignement du mesurage au cours des cent dernières années, évolution qui a été contemporaine de la naissance de la métrologie et d’importants progrès de la technologie des instruments de mesure. Les enjeux mêmes de l’enseignement du mesurage se sont peu à peu modifiés. En effet, on a cessé d’enseigner le «savoir-mesurer», pertinent au début du XXe siècle, au profit du traitement des données et de l’utilisation des données à fin de modélisation. Au-delà des enjeux, ce sont les notions enseignées qui ne sont plus les mêmes. Les termes d’erreur, de précision, de valeur vraie, etc. ne sont plus utilisés ou ont changé de sens.
Ce travail a pour source principale les études historiques réalisées pour le Bulletin de l’Union des physiciens à l’occasion de son centenaire en 2007.
Quelle est l'influence du contexte sur les raisonnements d'étudiants sur la mesure en physique ?
Authors: Maisch Clément , Ney Muriel , Balacheff Nicolas 
Published: June 2010

Dans cette étude, nous nous sommes intéressés à l’étape d’élaboration d’un protocole de mesure par les étudiants. Nous avons analysé les raisonnements des étudiants à partir des productions écrites recueillies dans trois types de situation : (1) un questionnaire lié à l’élaboration de protocole donné en TD, (2) l’élaboration d’un protocole en TP et (3) l’évaluation d’un protocole proposé en TP. Nous avons adapté les méthodologies développées dans différentes études antérieures sur les raisonnements d’étudiants sur la mesure à nos trois situations et obtenu un nouvel outil de classement. Cet outil a permis de classer les stratégies des étudiants en trois types de raisonnement : un raisonnement point (pour l’étudiant, il existe une vraie valeur qui peut être obtenue à l’aide d’une seule lecture) ; un raisonnement mixte (l’étudiant cherche à obtenir une mesure de la grandeur qui soit la plus proche possible d’une valeur de référence) ; un raisonnement ensemble (l’étudiant représente la quantité mesurée à l’aide d’une valeur et d’une indication de l’incertitude liée à cette valeur).
De plus, nous avons mis en évidence que les raisonnements mobilisés par chaque étudiant dans les situations de TP (2) et (3) semblent liés, alors que ces mêmes raisonnements sont indépendants de ceux utilisés dans la situation (1).
Modéliser les activités scientifiques à l'école élémentaire ?
Authors: Pierrard Marie-Anne 
Published: June 2010

What modelling of scientific activities in elementary school is pertinent ? Marie-Anne Pierrard
Classroom activities in elementary school science are described in the work of INRP teams in reference to a teaching model based on investigation and structuring. Can another sort of model (proposed by Britt-Mari Barth) be used to describe or elaborate these class activities ?
The INRP characteristics of both models are first defined, then B-M Barth's model Is used to describe elementary school activities in physics. As a result. It appears that this model can be efficient when defining the concept aimed at in the class or in finding out how the pupils progress In achieving it. But it does not take into account the specific aspects of science activities : the importance of the initial representations and the objectives connected with attitudes and competence which the investigation-structuration model does.
Obstacles et construction de situations didactiques en sciences expérimentales
Authors: Astolfi Jean-Pierre , Peterfalvi Brigitte 
Published: June 2010

Obstacles and the building of didactic situations in experimental science , Jean-Pierre Astolfi Brigitte Peterfalvi
Helping pupils to overcome the epistemological obstacles they run into is one of the basic challenges of “constructivist" science teaching. How should this kind of teaching be conceived ? The actions to be taken are necessarily oriented by certain characteristics of these obstacles : their transversal character, the way they appear In a network of ideas creating a system, and resist reification. Because of them, not too much can be expected of a single specific didactic mode of teaching.
Different strategies are possible, but they must all be flexible enough to allow pupils to Invest In their own ideas, and firmly directed enough to guarantee that the concept to be constructed is not lost sight of.
Une démarche pédagogique centrée sur l'analyse systémique dans l'enseignement agricole
Authors: Prévost Philippe 
Published: June 2010

Dans l’enseignement technique agricole, l'étude d'une démarche pédagogique, "l’approche globale de l’exploitation agricole", nous interroge sur les difficultés, non seulement de la transposition didactique, mais aussi de la mise en oeuvre par des enseignants ou l’appropriation par des apprenants d’un modèle systémique.
La prise en compte du but de l’apprentissage dans la démarche pédagogique est certainement un des facteurs essentiels de sa pertinence pour familiariser les acteurs avec un modèle systémique.
L'équation-bilan en chimie. Un concept intégrateur source de difficultés persistantes
Authors: Barlet Roger , Plouin Dominique 
Published: June 2010

La equación-de equilibrio en química. Un concepto integrador fuente de dificultades persistentes

La equación-de equilibrio, útil de base para todo trabajo cuantitativo en química, es considerado, equivocadamente, como una noción sin dificultades reales, para los alumnos.
Las investigaciones realizadas por numerosos autores, como la que hemos llevado a cabo a la universidad Joseph Fourier, muestran por tanto, que ese concepto integrador, acumula dificultades y concepciones. La puesta en perspectiva en la historia de ciencias, muestra que esas dificultades son esperadas.
Nos parece que una parte de concepciones manifestadas por los alumnos del liceo como por los estudiantes, pueden encontrar su raíz o su fuente en los problemas de simbolismo y de lenguaje. Formulamos pués, un cierto número de proposiciones didácticas fijadas sobre una puesta en orden, sobre el lenguaje.