1,720,959 research outputs found
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
Development of protein kinase CK2 inhibitors targeting the α/β interaction : design, synthesis, mechanistic study and cellular
No full textLa protéine kinase CK2, au centre de la recherche biomédicale depuis plus de 50 ans, est une enzyme pléiotrope qui s’immisce massivement dans de nombreuses voies de signalisation et qui se distingue par différentes propriétés inhabituelles, notamment sur son organisation moléculaire au sein de sa structure quaternaire. Elle correspond à un complexe hétéro-tétramérique (ou holoenzyme), formé par l’association dynamique de deux sous-unités catalytique (CK2α et/ou CK2α’) avec deux sous-unités régulatrices (CK2β). Une expression exacerbée dans différentes lignées cancéreuses, une aptitude à agir comme un suppresseur de l’apoptose et à promouvoir la survie cellulaire, associée à une forte implication pour renforcer un phénotype résistant aux médicaments, sont autant de caractéristiques qui soulignent l’intérêt pour la CK2 en tant que cible thérapeutique. La plupart des inhibiteurs identifiés au cours des deux dernières décennies sur l’holoenzyme sont des molécules ATP- mimétiques, dont l’une d’entre elle, le CX4945 (silmitasertib), s’est hissée jusqu’en essai clinique de phase II. Généralement, avec ce mode d’action, ces molécules sont pourvues d’un profil de toxicité favorable, dû à un manque de spécificité pour leur cible et sont sujettes à l’apparition de résistances qui viennent compromettre leur réussite en clinique. Le CX4945 ne fait pas exception puisque différentes études ont montré sa capacité à inhiber plus d’une vingtaine de protéines kinases, autres que la CK2. Partant de ce constat, de nouvelles stratégies sont proposées pour moduler l’activité des enzymes essentielles à la survie des cellules cancéreuses, sans cibler le site catalytique. La régulation, la spécificité de ses substrats et la localisation subcellulaire de la CK2 reposent sur son interaction réversible CK2α/CK2β. Plus récemment, les premiers antagonistes chimiques de cette interaction ont été décrits par notre laboratoire. Ces molécules déstabilisent la formation de l’holoenzyme, ce qui altère partiellement l'activité de la CK2. Toutefois, l’efficacité limitée de ces composés n’a pas permis de comprendre leurs effets au niveau cellulaire. A partir de leurs données structurales et en combinant le criblage de fragments guidé par des expériences RMN, des études de modélisation et des approches de pharmacomodulation plus classiques, nous avons développé au cours de cette étude une seconde génération d’inhibiteurs de l’interaction CK2α/CK2β, capables de perturber la formation du complexe protéique avec une affinité inférieure au micromolaire. Notre étude démontre l’intérêt thérapeutique d’inhiber la CK2 avec ce mode d’action à l’aide de différents modèles cellulaires, apporte les premières preuves de concept ex vivo, en permettant de confirmer un profil pharmacologique adapté à de prochaines évaluations in vivoFor more than 50 years, the pleiotropic protein kinase CK2 has been widely investigated and was uncovered to play various roles in several distinct signaling pathways. Most notably, CK2 presents a very unique quaternary structure, consisting of two catalytic subunits (CK2α and/or CK2α’) which dynamically associate with two regulatory subunits (CK2β) in order to form the tetrameric complex. This protein appeared as a promising therapeutic target, due to its overexpression in numerous cancer cell lines, in addition to both its anti-apoptotic and antitumor drug resistance activities. Most of CK2 inhibitors, engineered these past few years, are ATP-competitive small molecules, among which the CX4945 (silmitasertib) managed to reach Phase II of clinical trials. However, it is well established in the literature that ATP-competitive agents exhibit significant toxicity owing to their lack of specificity and other issues such as resistances phenomenon, which can drastically hinder their development. The CX4945 is a marked example, being described as interacting with more than 20 others different protein kinases. Therefore, novel therapeutic strategies have been recently designed as for instance to selectively target the protein-protein interactions (PPIs), which are critical to cancer cells survival. The reversible CK2α/CK2β interaction is known to regulate and control CK2 localization, in addition to modulate substrate specificity. More recently, the first in class CK2-targeted PPIs antagonists were synthesized in our center, which impacted the holoenzyme association and partially altered CK2 activity. However, the very limited efficacy of such compounds did not allow to further study their in cellulo effects. Combining fragment-based drug design, NMR and structural studies, as well as pharmacomodulation approaches, we report in this work the synthesis of the second generation of PPIs CK2α/CK2β inhibitors, which are able to impede the tetrameric complex association with sub- micromolar affinities. Our studies also demonstrate a real therapeutic interest in inhibiting CK2 PPIs on a wide array of ex vivo cellular models, and finally shed light on the pharmacological profile of this series which could be adapted to in vivo models in a near futur
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
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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