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    Role ans molecular mechanisms of action of Mycobacterium tuberculosis cell envelope lipids in virulence

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    Mycobacterium tuberculosis est la bactérie responsable de la tuberculose (TB), une infection pulmonaire grave. La TB est un problème majeur de santé publique mondial ; un tiers de la population mondiale est porteur de M. tuberculosis et l'émergence de formes de TB résistantes aux antibiotiques confirme la nécessité de développer de nouvelles approches thérapeutiques. Pour atteindre cet objectif, il est crucial de mieux comprendre les mécanismes infectieux de M. tuberculosis. L'équipe de C. Guilhot s'intéresse aux lipides de l'enveloppe bactérienne impliqués dans la virulence de M. tuberculosis, en particulier lors de l'interaction du bacille avec les macrophages de l'hôte. Un type de lipide en particulier s'est démarqué pour son rôle crucial dans cette interaction : les Dimycocérosates de Phthiocérol (DIM). Malgré leur importance, le mécanisme d'action moléculaire des DIM n'est toujours pas connu. Les objectifs de ma thèse ont été 1) d'étudier le rôle des DIM dans le trafic intracellulaire de M. tuberculosis au sein du macrophage, et 2) de comprendre les mécanismes d'action des DIM dans la virulence. Par une combinaison de méthodes biologiques et biophysiques, nous avons montré que les DIM contribuent à l'induction de la rupture du phagosome et de l'apoptose du macrophage infecté par M. tuberculosis, en collaboration avec un autre facteur majeur de virulence bactérien, ESAT-6. Au niveau moléculaire, nous avons confirmé que les DIM sont transférés dans la membrane du macrophage au contact avec la bactérie, et y induisent une rigidification membranaire locale. Nous avons aussi montré que les DIM dans une membrane sont capables de potentialiser l'activité membranolytique d'ESAT-6 et d'autre(s) facteur(s) encore non identifiés. Les DIM ont un rôle pléiotropique dans l'interaction de M. tuberculosis avec le macrophage. Leur mécanisme d'action impliquerait des modifications des propriétés biophysiques membranaires, modifiant l'activité des effecteurs membranaires bactériens et potentiellement de l'hôte. Ces travaux ouvrent la voie à l'étude du mécanisme d'action d'autres lipides de virulence dont certains pourraient également s'insérer dans la membrane du macrophage.Mycobacterium tuberculosis is the bacterium responsible for tuberculosis (TB), a severe respiratory disease. TB is a major public health threat; one third of the world's population is latently infected by M. tuberculosis, and the emergence of antibiotic-resistant forms of TB confirms that there is a need to develop new therapeutic approaches to control the spread of TB. However, in order to attain that goal, it is crucial to decipher the infectious mechanisms of M. tuberculosis. Research in the team of C. Guilhot focuses on lipids from the envelope of M. tuberculosis which are involved in virulence, in particular those implicated in the interaction of the bacteria with host macrophages. One of these lipids stands out for its crucial role in this interaction: Phthiocerol Dimycocerosate (DIM). Despite its importance, the molecular mechanism of action of DIM is still unknown. The objectives of my PhD were 1) to study the role of DIM in the intracellular trafficking of M. tuberculosis in macrophages, and 2) to decipher the molecular mechanism of action of DIM. By a combination of biological and biophysical techniques, we showed that DIM contributes to phagosomal rupture and induction of apoptosis in macrophages infected with M. tuberculosis, in collaboration with another major virulence factor: ESAT-6. At the molecular level, we confirmed that DIM is transferred to the membrane of the macrophage on contact with M. tuberculosis and induces a local membrane rigidification around the point of contact with the bacterium. We observed that DIM incorporated in membranes is able to promote the membranolytic activity of ESAT-6, and other yet unidentified bacterial factor(s). DIM has a pleiotropic role in the interaction between M. tuberculosis and macrophages, presumably through alterations of the membrane's biophysical properties that influence the activity of membrane effectors from both the bacteria and the host. Thus, this work paves the way for the study of the mechanisms of action of other virulence lipids, some of which could also be inserted in the macrophage membrane

    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

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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