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    VEGF-A et phénotypes intermédiaires des maladies cardiovasculaires : une approche de génomique fonctionnelle

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    Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has been linked to cardiovascular diseases (CVDs) and related predisposing statuses such as metabolic syndrome (MetS).The identification of genetic variants that influence the VEGF circulating levels and their associations with MetS and adhesion and inflammation molecules could enable us to have a comprehensive approach of the relationship of this molecule with CVDs. Therefore, we aimed at first to investigate the genetic background of VEGF levels, via a genome wide association analysis, and the pre-analytical and analytical variation factors of VEGF levels measurements before examining the implication of this molecule in inflammation and in MetS. Also, we examined the differences of MetS between Iranian (MASHHAD cohort) and French (STANISLAS cohort) populations. The main findings of this thesis are: 1) the identification of 4 genetic variants(rs6921438, rs4416670, rs6993770 and rs10738760) that explain 47.6% of circulating VEGF levels, 2) the associations of VEGF and its identified genetic variants with adhesion and inflammation molecules such as ICAM-1, E and L selectins , TNF-alpha, IL-6 and CRP at protein and transcription levels, 3) the association of VEGF-related polymorphism rs10738760 with MetS, 4) the relationship between VEGF regulatory variant, rs6921438, and LDL-C and HDL-C,5) the proposition of the best conditions for measuring both circulating VEGF (serum being the most stable anticoagulant) and its gene expression by reducing time between blood collection and centrifugation, and by avoiding multiple freeze-thaw cycles,6) a high prevalence of MetS in Iranian women. Our results propose the biological connections between VEGF, inflammation and adhesion molecules, lipids and MetSLe facteur de croissance de l'endothélium vasculaire (VEGF) est une cytokine multifonctionnelle qui a été liée aux maladies cardiovasculaires (MCV) et à des divers troubles/ facteurs de risque cardiovasculaires tel que le syndrome métabolique (SM). L'identification de variants génétiques qui agissent sur les taux de VEGF circulant et leurs associations avec le SM et les molécules d'adhésion et d'inflammation pourraient permettre la compréhension des liens entre les taux de VEGF et les MCV. Par conséquent nous avons recherché l'origine génétique des taux de VEGF, via une étude d'association pangénomique, et les facteurs de variation pré-analytiques et analytiques influant les taux de VEGF mesurés avant d'étudier les implications de cette molécule dans l'inflammation et le SM. Nous avons également examiné le profil du SM dans des populations françaises (cohorte STANISLAS) et iraniennes (cohorte MASHHAD). Les principaux résultats de cette thèse sont : 1) l'identification de variants génétiques rs6921438, rs4416670, rs6993770 et rs10738760 expliquant 47.6% des taux de VEGF circulant, 2) l'association du VEGF et des variants génétiques identifiés avec des molécules d'adhésion et d'inflammation telles que ICAM-1,sélectines E et L,TNF-alpha, IL-6 et CRP au niveau protéique et transcriptomique, 3) l'association du rs10738760 avec le SM, 4) la relation entre le rs6921438 et le HDL-C et le LDL-C, 5) la détermination optimale à la fois des taux de VEGF (le sérum serait plus stable que le plasma) et de son expression génétique en proposant une durée minimale entre le recueil du sang et sa centrifugation, et en évitant des cycles de gel/dégel répétés. 6) la prévalence élevée du SM chez les femmes iraniennes. Nos résultats proposent des liens biologiques entre le VEGF et les molécules d'inflammation et l'adhésion, les lipides et le S

    VEGF-A and intermediate phenotypes of cardiovascular diseases : a functional genomics approach

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    Le facteur de croissance de l'endothélium vasculaire (VEGF) est une cytokine multifonctionnelle qui a été liée aux maladies cardiovasculaires (MCV) et à des divers troubles/ facteurs de risque cardiovasculaires tel que le syndrome métabolique (SM). L'identification de variants génétiques qui agissent sur les taux de VEGF circulant et leurs associations avec le SM et les molécules d'adhésion et d'inflammation pourraient permettre la compréhension des liens entre les taux de VEGF et les MCV. Par conséquent nous avons recherché l'origine génétique des taux de VEGF, via une étude d'association pangénomique, et les facteurs de variation pré-analytiques et analytiques influant les taux de VEGF mesurés avant d'étudier les implications de cette molécule dans l'inflammation et le SM. Nous avons également examiné le profil du SM dans des populations françaises (cohorte STANISLAS) et iraniennes (cohorte MASHHAD). Les principaux résultats de cette thèse sont : 1) l'identification de variants génétiques rs6921438, rs4416670, rs6993770 et rs10738760 expliquant 47.6% des taux de VEGF circulant, 2) l'association du VEGF et des variants génétiques identifiés avec des molécules d'adhésion et d'inflammation telles que ICAM-1,sélectines E et L,TNF-alpha, IL-6 et CRP au niveau protéique et transcriptomique, 3) l'association du rs10738760 avec le SM, 4) la relation entre le rs6921438 et le HDL-C et le LDL-C, 5) la détermination optimale à la fois des taux de VEGF (le sérum serait plus stable que le plasma) et de son expression génétique en proposant une durée minimale entre le recueil du sang et sa centrifugation, et en évitant des cycles de gel/dégel répétés. 6) la prévalence élevée du SM chez les femmes iraniennes. Nos résultats proposent des liens biologiques entre le VEGF et les molécules d'inflammation et l'adhésion, les lipides et le SMVascular endothelial growth factor (VEGF) is a multifunctional cytokine that has been linked to cardiovascular diseases (CVDs) and related predisposing statuses such as metabolic syndrome (MetS).The identification of genetic variants that influence the VEGF circulating levels and their associations with MetS and adhesion and inflammation molecules could enable us to have a comprehensive approach of the relationship of this molecule with CVDs. Therefore, we aimed at first to investigate the genetic background of VEGF levels, via a genome wide association analysis, and the pre-analytical and analytical variation factors of VEGF levels measurements before examining the implication of this molecule in inflammation and in MetS. Also, we examined the differences of MetS between Iranian (MASHHAD cohort) and French (STANISLAS cohort) populations. The main findings of this thesis are: 1) the identification of 4 genetic variants(rs6921438, rs4416670, rs6993770 and rs10738760) that explain 47.6% of circulating VEGF levels, 2) the associations of VEGF and its identified genetic variants with adhesion and inflammation molecules such as ICAM-1, E and L selectins , TNF-alpha, IL-6 and CRP at protein and transcription levels, 3) the association of VEGF-related polymorphism rs10738760 with MetS, 4) the relationship between VEGF regulatory variant, rs6921438, and LDL-C and HDL-C,5) the proposition of the best conditions for measuring both circulating VEGF (serum being the most stable anticoagulant) and its gene expression by reducing time between blood collection and centrifugation, and by avoiding multiple freeze-thaw cycles,6) a high prevalence of MetS in Iranian women. Our results propose the biological connections between VEGF, inflammation and adhesion molecules, lipids and Met

    VEGF-A and intermediate phenotypes of cardiovascular diseases (a functional genomics approach)

    No full text
    Le facteur de croissance de l'endothélium vasculaire (VEGF) est une cytokine multifonctionnelle qui a été liée aux maladies cardiovasculaires (MCV) et à des divers troubles/ facteurs de risque cardiovasculaires tel que le syndrome métabolique (SM). L'identification de variants génétiques qui agissent sur les taux de VEGF circulant et leurs associations avec le SM et les molécules d'adhésion et d'inflammation pourraient permettre la compréhension des liens entre les taux de VEGF et les MCV. Par conséquent nous avons recherché l'origine génétique des taux de VEGF, via une étude d'association pangénomique, et les facteurs de variation pré-analytiques et analytiques influant les taux de VEGF mesurés avant d'étudier les implications de cette molécule dans l'inflammation et le SM. Nous avons également examiné le profil du SM dans des populations françaises (cohorte STANISLAS) et iraniennes (cohorte MASHHAD). Les principaux résultats de cette thèse sont : 1) l'identification de variants génétiques rs6921438, rs4416670, rs6993770 et rs10738760 expliquant 47.6% des taux de VEGF circulant, 2) l'association du VEGF et des variants génétiques identifiés avec des molécules d'adhésion et d'inflammation telles que ICAM-1,sélectines E et L,TNF-alpha, IL-6 et CRP au niveau protéique et transcriptomique, 3) l'association du rs10738760 avec le SM, 4) la relation entre le rs6921438 et le HDL-C et le LDL-C, 5) la détermination optimale à la fois des taux de VEGF (le sérum serait plus stable que le plasma) et de son expression génétique en proposant une durée minimale entre le recueil du sang et sa centrifugation, et en évitant des cycles de gel/dégel répétés. 6) la prévalence élevée du SM chez les femmes iraniennes. Nos résultats proposent des liens biologiques entre le VEGF et les molécules d'inflammation et l'adhésion, les lipides et le SMVascular endothelial growth factor (VEGF) is a multifunctional cytokine that has been linked to cardiovascular diseases (CVDs) and related predisposing statuses such as metabolic syndrome (MetS).The identification of genetic variants that influence the VEGF circulating levels and their associations with MetS and adhesion and inflammation molecules could enable us to have a comprehensive approach of the relationship of this molecule with CVDs. Therefore, we aimed at first to investigate the genetic background of VEGF levels, via a genome wide association analysis, and the pre-analytical and analytical variation factors of VEGF levels measurements before examining the implication of this molecule in inflammation and in MetS. Also, we examined the differences of MetS between Iranian (MASHHAD cohort) and French (STANISLAS cohort) populations. The main findings of this thesis are: 1) the identification of 4 genetic variants(rs6921438, rs4416670, rs6993770 and rs10738760) that explain 47.6% of circulating VEGF levels, 2) the associations of VEGF and its identified genetic variants with adhesion and inflammation molecules such as ICAM-1, E and L selectins , TNF-alpha, IL-6 and CRP at protein and transcription levels, 3) the association of VEGF-related polymorphism rs10738760 with MetS, 4) the relationship between VEGF regulatory variant, rs6921438, and LDL-C and HDL-C,5) the proposition of the best conditions for measuring both circulating VEGF (serum being the most stable anticoagulant) and its gene expression by reducing time between blood collection and centrifugation, and by avoiding multiple freeze-thaw cycles,6) a high prevalence of MetS in Iranian women. Our results propose the biological connections between VEGF, inflammation and adhesion molecules, lipids and MetSMETZ-SCD (574632105) / SudocNANCY1-Bib. numérique (543959902) / SudocNANCY2-Bibliotheque electronique (543959901) / SudocNANCY-INPL-Bib. électronique (545479901) / SudocSudocFranceF

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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
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