1,720,956 research outputs found

    Generation of nanobodies for immunotherapy applications

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    L’immunothérapie est une approche thérapeutique qui consiste à restaurer les fonctions anti-tumorales du système immunitaire pour qu’il soit à nouveau capable d’éliminer les cellules cancéreuses. Pour cela, différentes stratégies sont étudiées : l’une d’entre elles consiste à cibler des récepteurs inhibiteurs présents à la surface des cellules immunitaires infiltrées dans les tumeurs de façon à réactiver leurs fonctions. L’entreprise Innate Pharma développe des anticorps monoclonaux capables de restaurer les fonctions immunitaires de cellules effectrices de l’immunité innée. Le but de la collaboration était de générer des sdAbs (single-domain Antibodies), fragments d’anticorps dérivés de camélidés, capables de bloquer des interactions de type « immune checkpoint ». Ces anticorps à domaine unique sont notamment capables de lier des épitopes inaccessibles aux anticorps conventionnels tels que des cavités. Dans ce manuscrit, les résultats concernant deux de ces projets sont exposés : la modulation de l’axe inhibiteur SIRPα/CD47 et le blocage de l’interaction réalisée entre les récepteurs Siglec-7/-9 et leurs ligands sialylés. Lors de ces travaux, plusieurs sdAbs ciblant les récepteurs d’intérêt ont été sélectionnés grâce à la technologie du phage display. Ces molécules monovalentes ont été caractérisées puis clonées en différents formats multivalents de façon à améliorer leur affinité par effet d’avidité, et ainsi potentialiser leur efficacité de blocage. Enfin, plusieurs tests fonctionnels ont été réalisés pour évaluer l’effet de ces molécules sur les fonctions effectrices de différentes cellules du système immunitaire.Immunotherapy is a therapeutic approach which consists in restoring anti-tumoral functions of the immune system for eliminating cancer cells. For this, several strategies are developed: one of them is to target inhibitory receptors at the surface of effector cells in order to reactivate their functions in the tumor microenvironment.The company Innate pharma develops monoclonal antibodies able to restor immune functions of innate effector cells. The aim of the collaboration was to generate single-domain Antibodies (sdAbs), antibody fragments derived from camelids, which have the capacity of blocking interactions such as immune checkpoints. These sdAbs have several useful characteristics in terms of stability, production and especially in epitope binding. Indeed, because of their small size, they are able to bind on epitopes which are not accessible to conventional antibodies.In this manuscript, the results of two projets are reported: the modulation of the inhibitory axis SIRPα/CD47 and the blocking of the interaction between the receptors Siglec-7/-9 and their sialylated ligands. In these studies, several sdAbs targeting the receptors of interest were isolated by selection using phage display technology. These monovalent molecules were characterized to determine their specificity and estimate their binding and blocking capacities. Best candidates were cloned into several multivalent formats to optimize their affinity by avidity effect and to potent their blocking efficacy. Finally, several functional assays were performed to evaluate the efficacy of these multivalent constructions to restore immune functions of several effector cells

    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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