La fabrication discursive de l’université : comptes rendus et rapports scientifiques en diachronie. Présentation

Le présent dossier vise à saisir les transformations qui affectent l’Université depuis les années 1970 jusqu’à aujourd’hui, via l’analyse de deux genres de discours qui en règlent et en organisent l’activité : les comptes rendus de conseils d’administration (CA) et les rapports de recherche des laboratoires (rapports d’activité et rapports d’auto-évaluation). Il présente, du point de vue de l’analyse du discours (ci-après AD), l’état des recherches en cours dans le cadre du projet ArchivU, pr..

Le risque : un modèle conceptuel d'intégration

The following project report is the first of a sequence which will focus on integrated risk management. This report presents a conceptual model which goal is to define the concept of risk. This conceptual model integrates the definitions of multiple domains having an interest in risk management. With the model, a terminology is proposed. This conceptual model is a foundation upon which it will be possible to exchange methods and measures of risk between domains. Ce rapport de projet est le premier d'une série qui s'intéressera à la gestion intégrée du risque. Dans l'objectif de répondre à la question « qu'est-ce que le risque? », un modèle conceptuel définissant le concept du risque est proposé. Ce modèle conceptuel intègre les définitions du risque de différentes disciplines. Une terminologie a été élaborée pour accompagner le modèle. Ce modèle conceptuel tente d'élaborer une base à partir de laquelle pourra se faire l'échange de méthodes et de mesures entre les domaines s'intéressant au risque.Risk, integrated risk management, definition, integration, Risque, gestion intégrée du risque, définition, intégration

Envision M5 Venus orbiter proposal

EnVision [1,2] is a Venus orbiter mission that will determine the nature and current state of geological activity on Venus, and its relationship with the atmosphere, to understand how and why Venus and Earth evolved so differently. Envision is a finalist in ESA’s M5 Space Science mission selection process, and is being developed in collaboration with NASA, with the sharing of responsibilities currently under assessment. It is currently in Phase A study; final mission selection is expected in June 2021. If selected, EnVision will launch by 2032 on an Ariane 6.2 into a six month cruise to Venus, followed by aerobraking, to achieve a near-circular polar orbit for a nominal science phase lasting at least 4 Venus sidereal days (2.7 Earth years)

Translocation breakpoints in FHIT and FRA3B in both homologs of chromosome 3 in an esophageal adenocarcinoma

Common fragile sites have been proposed to play a mechanistic role in chromosome translocations and other rearrangements in cancer cells in vivo based on their behavior in vitro and their co-localization with cancer translocation breakpoints. This hypothesis has been the subject of controversy, because associations have been made at the chromosomal level and because of the large number of both fragile sites and cancer chromosome breakpoints. Tests of this hypothesis at the molecular level are now possible with the cloning of common fragile site loci and the use of fragile site clones in the analysis of rearranged chromosomes. FRA3B, the most frequently seen common fragile site, lies within the large FHIT gene. It is now well established that this region is the site of frequent, large intragenic deletions and aberrant transcripts in a number of tumors and tumor cell lines. In contrast, only one tumor-associated translocation involving the FHIT gene has been reported. We have found translocations in both homologs of chromosome 3 in an early-passage esophageal adenocarcinoma cell line. This cell line showed no normal FHIT transcripts by reverse transcription polymerase chain reaction. Subsequent chromosome analysis showed translocations of the short arms of both homologs of chromosome 3: t(3;16) and t(3;4). The breakpoints of both translocations were shown by fluorescence in situ hybridization and polymerase chain reaction to be in the FHIT gene, at or near the center of the fragile site region. Using rapid amplification of cDNA ends with FHIT primers, a noncoding chimeric transcript resulting from t(3;16) was identified. These data provide direct support for the hypothesis that FRA3B , and likely other common fragile sites, may be “hot spots” for translocations in certain cancers, as they are for deletions, and that such translocations have the potential to form abnormal chimeric transcripts. In addition, the results suggest selection for loss of a functional FHIT gene by the translocation events. © 2001 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35130/1/1095_ftp.pd

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Automate de fabrication des anticancéreux injectables (qualification opérationnelle)

PARIS-BIUP (751062107) / SudocSudocFranceF