1,720,976 research outputs found
Caractérisation biochimique et structurale de la sélénoprotéine N et étude de l’impact de son dysfonctionnement dans le tissu pancréatique
No full textChez l'homme, des mutations dans le gène SELENON, codant pour la sélénoprotéine N (SelenoN), provoquent un groupe de maladies musculaires héréditaires appelés myopathies liées à SELENON. Les mécanismes pathologiques à l'origine de ces myopathies sont mal compris, car la fonction catalytique de SelenoN reste incomprise. L'utilisation de modèles animaux a révélé l'importance de SelenoN dans le développement, la maintenance et la régénération des muscles. En outre, il a été démontré que SelenoN joue un rôle important dans le contrôle du stress oxydatif dans le réticulum endoplasmique et le maintien de l'homéostasie du calcium dans la cellule, ainsi qu'un lien a été établi avec la fonction mitochondriale. Malgré ces progrès passionnants concernant l'implication physiologique du SelenoN dans le tissu musculaire, l'activité catalytique de cette enzyme est encore inconnue et aucun traitement n'est disponible. Ce projet vise à développer des études in vitro et in vivo pour caractériser l'activité enzymatique de SelenoN et son contexte moléculaire et cellulaire. Tout d'abord, nous avons pu exprimer et purifier une forme recombinante pure et soluble de SelenoN. Les analyses ont montré que SelenoN lie une petite molécule, qui est en cours de caractérisation. La résolution de la structure 3D de SelenoN a permis de mieux comprendre l’organisation du site catalytique de la protéine. En parallèle, l'environnement cellulaire et les partenaires de SelenoN ont été étudiés en utilisant le marquage proximal (BioID) in cellulo, montrant une localisation spécifique dans le réticulum endoplasmique, liée au repliement des protéines et à la réponse au stress du RE. Enfin, l'utilisation in vivo du modèle SelenoN-/-mice a permis de mettre en évidence un phénotype métabolique dépendant du sexe. Ces études intégratives ont fourni des informations clés sur les bases moléculaires et physiopathologiques des myopathies liées à SelenoN et ouvriront la possibilité au développement des voies de thérapies.In humans, mutations in the SELENON gene, encoding selenoprotein N (SelenoN), cause a group of inherited muscular disorders termed SELENON-related myopathies. The pathogenic mechanisms behind these muscular diseases are poorly understood since the catalytic function of SelenoN remains elusive. The use of animal models revealed the importance of SelenoN in muscle development, maintenance, and regeneration. Moreover, SelenoN has been shown to play a role in oxidative stress control in the endoplasmic reticulum and maintenance of calcium homeostasis in the cell, as well as a link with mitochondrial function. Despite these exciting progresses regarding the physiological involvement of SelenoN in muscle tissue, the catalytic activity of this enzyme is still unknown, and no treatment is available. This project aims to develop in vitro and in vivo studies to characterize SelenoN enzymatic activity and the molecular and cellular context of this activity. Firstly, we were able to express and purify pure and soluble recombinant form of SelenoN. Analysis showed that SelenoN binds a small molecule, currently under characterization. The resolution of SelenoN 3D structure provided new insight and understanding of the catalytic site of the protein. In parallel, SelenoN cellular environment and partners were investigated using proximal labeling (BioID) in cellulo, showing a specific localization within the endoplasmic reticulum, related to protein folding and ER stress response. Finally, in vivo using SelenoN-/-mice model demonstrated a gender specific metabolic phenotype. These integrative studies provided key information about the molecular and physio-pathological basis of SELENON-related myopathies and will pave the way for therapy development
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Heart failure : epidemiological, etiological aspects and therapeutic innovations
No full textL'insuffisance cardiaque est une entité clinique complexe impliquant une stimulation neuro-hormonale et prédominance de l'activité du système sympathique. Elle représente le stade terminal des multiples pathologies cardiaques tels que les cardiomyopathies, l'arythmie, les maladies coronariennes et valvulaires. En pratique courante, on divise l'insuffisance cardiaque en 2 types : à fraction d'éjection préservée ou réduite. Malgré la progression remarquable des moyens thérapeutiques, l'insuffisance cardiaque reste une cause majeure de décès dans le monde entier. La maladie coronarienne obstructive est l'étiologie la plus commune et elle est régulièrement recherchée par les cliniciens, en particulier en cas d'altération de la fraction d'éjection du ventricule gauche. Par contre, le niveau d'évidence qui supporte l'intérêt de la revascularisation coronarienne dans le contexte d'insuffisance cardiaque est faible. Cette thèse vise à décrire les caractéristiques des patients avec dysfonction ventriculaire puis préciser la prévalence de la maladie coronarienne associée ainsi que les caractéristiques de l'insuffisance cardiaque ischémique versus non ischémique et finalement évaluer l'effet de la revascularisation sur la mortalité globale dans un contexte d'insuffisance cardiaque ischémique. Cette étude a identifié le sexe masculin comme un facteur prédicteur de dysfonction systolique tandis que l'âge supérieur à 65 ans comme un facteur de risque pour dysfonction diastolique. Elle retrouve une maladie coronarienne obstructive chez plus que 50 % des patients avec insuffisance cardiaque soit à fraction d'éjection préservée (56.1 %) ou réduite (55.7 %) référés pour coronarographie diagnostique devant une découverte récente d'une insuffisance cardiaque ou décompensation aiguë d'une insuffisance cardiaque chronique. La prévalence observée de maladie coronarienne chez la population avec insuffisance cardiaque est de 55.8 %. Il existe une association significative et positive entre l'âge, le sexe masculin et le diabète d'une part et l'insuffisance cardiaque ischémique d'autre part. Pas de différences ont été observées entre les patients avec insuffisance cardiaque a fraction d'éjection préservée ischémique versus non ischémique tandis que les sujets avec insuffisance cardiaque à fraction d'éjection réduite ischémique présentent plus des facteurs de risque cardiovasculaires que les non ischémiques. Après un suivi de 2.5 ans à peu près, la mortalité globale a été inférieure chez les patients traités par revascularisation soit par angioplastie percutanée ou soit par pontage aortocoronarien en comparaison à ceux sous traitement médical optimal seule (26.7 % vs 22.2 %, p=0.208). La courbe Kaplan-Meier ne révèle pas une différence de survie entre les groupes malgré la stratification ni sur le type de l'insuffisance cardiaque et ni sur les modalités de revascularisation. On clarifie que les études qui ont montré les bénéfices de la revascularisation sur la survie s'était strictement après une longue durée de suivi dépassant les 5 ans. On conclut que sur la population étudiée, il apparait que la revascularisation coronarienne permet de réduire le taux de mortalité sans effet significatif sur la survie dans un contexte d'insuffisance cardiaque en dehors des syndromes coronariens aigus et sur un court terme.Heart failure (HF) is a complex clinical entity incorporating neuro-hormonal stimulation and sympathetic overdrive that get worse progressively. It represents the end stage of multiple heart diseases like cardiomyopathies, arrythmias, coronary artery disease and valvular disease. Practically, it is divided into two main types: HF with preserved ejection fraction (HFpEF) or HF with reduced ejection fraction (HFrEF). Regardless the remarkable progression of the available therapeutic strategies, HF remains a major cause of death with a large burden on public health systems. Noteworthy that obstructive coronary artery disease is the most common cause of HF and it is regularly assessed by health care practitioners, especially in the setting of HFrEF. However, there are a lack of strong evidence to support additional benefits of coronary revascularization over optimal medical treatment in HF-patients. In this thesis, we firstly aim to describe the characteristics of patients with left ventricular dysfunction. Then, we focused on the prevalence of CAD in HF-patients and characteristics of ischemic versus non ischemic HF. Lastly, we evaluate the effect of coronary revascularization in ischemic HF on all-cause mortality after 2 years of follow-up. In the present thesis, we identified male sex as an independent predictor of left ventricular systolic dysfunction and age above 65-year-old as a risk factor of diastolic dysfunction. A significant CAD was found in more than 50% of patients either with HFpEF(56.1%) or HFrEF(55.7%) who underwent coronary angiography for recent diagnosis of HF or acute decompensation of chronic HF. The overall prevalence of CAD in HF patients was 55.8%. This study has also revealed a significant positive association between age, male sex, and diabetes mellitus on one hand and ischemic HF on other hand. No differences between ischemic versus non ischemic HFpEF have been revealed whereas patients with ischemic HFrEF expressed more cardiovascular risk factors compared to non-ischemic HFrEF. Furthermore, age and dyslipidemia were the main different parameters between ischemic HFpEF versus ischemic HFrEF groups. Lastly, the all-cause mortality rate was lower in patients who underwent coronary revascularization either by percutaneous coronary intervention or coronary artery bypass graft compared to those who received optimal medical therapy alone over a mean follow-up period of 2.5±1.1 years (26.7% vs 22.2%, p=0.208). However, the Kaplan-Meier curve showed no significant difference in free event survival analysis in the course of time (p=0.208) even though after stratification neither by the types of HF nor the modalities of revascularization. Lastly, we highlight on the fact that available data in literature that supported positive survival effects of coronary revascularization in HF-patients were only observed after a long term of follow-up. We conclude that in this study population, it seems that coronary revascularization performed over an optimal tolerated medical treatment reduced the all-cause mortality rate but without providing significant advantage on survival in HF-patients outside the setting of acute coronary syndrome and after a short-term follow-up (almost equal to 2.5-years)
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
- …
