2 resultados para Visual and acoustic signaling


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This interdisciplinary study examines the contribution that a book-review magazine makes to the cultural identity of its readers. It is the result of reflections on the cultural work of Books in Canada , on whether or not this periodical was a cultural worksite and if that is the case how it performed that cultural work. In addition, it interrogates factors that may have contributed to the magazine's demise. The study affirms that Books in Canada, a cultural enterprise from 1971 to 2008, mirrored and helped to shape book and literary culture in Canada through its circulation, through the personalities of its editors, through its front covers and through its reviewers and their reviews. Furthermore, it proposes that the demise of the enterprise was due to a combination of factors. The study begins with an introduction to book reviewing and special-interest magazines. Chapter I examines the interplay between selected visual and textual contents published in Books in Canada in its founding years. These components reflected and helped to fuel the cultural nationalism that was sweeping Canada subsequent to the 1967 World's Fair in Montreal. There were also persistent rumours and comments about the magazine that caused certain"cracks in the foundation" to appear. Chapter II compares the aims and editorial challenges of Val Clery, founder of Books in Canada , with those of Adrien Thério, founder of Lettres québécoises, and of the editors of the magazines' twentieth-anniversary issues, Paul Stuewe in the case of the former and André Vanasse in the case of the latter. Evidence in the content of the magazine, editorial and otherwise, indicated that the"contracts" that the editors made with their readers over the years were similar, to reflect and shape a cultural identity, but the result of their"projects," that is, the nature of those identities, was distinctly different. Evidently then, personal aims, preferences and political leanings of editors can have a major impact on the content of a book-review magazine and thus on the cultural work that it does. Therefore, in Chapter III, I focus on selected contents published during the tenures of two of Books in Canada 's key editors, Paul Stuewe and Olga Stein, in order to understand ways that their choices constituted a form of cultural work. The second part of this chapter moves from an analysis of the cultural work of editors to an examination of the cultural work of reviewers. Here, through a close-reading of a selection of reviews published in Books in Canada, and in other periodicals, I argue that reviewers do cultural work in the way that they negotiate their presence in a review, and in how they signal that presence through lexical choices and through the degree of intellectual interaction that they invite. Intellectual interaction is at the core of Chapter IV.This chapter consists of close readings of some of the"billboards" of the enterprise, that is, the front covers of Books in Canada , in order to show how these important components do cultural work by requiring readers to make an intellectual leap from image to text. Chapter V suggests that book reviews, the company's"bills of goods," do cultural work in much the same way as the paratexts of a book. One of my own reviews is offered as a case-study along with a number of other reviews of how central components of a book-review magazine do cultural work through the illocutionary force of their sentences. The first part of Chapter VI, the final chapter, measures the legacy of the magazine, in particular, the annual Books in Canada First Novel Award. Created in 1976, this prize is awarded to the author of the novel judged by a Books in Canada prize committee to be the best first novel in English of the year. The second part of Chapter VI sheds light on factors that may have contributed to the closure of the enterprise, including the copyright uproar that accompanied the agreement that Adrian Stein, publisher of Books in Canada and Olga Stein's husband, made in 2001 with the online book merchant, Amazon.com. Furthermore, this penultimate section of the study suggests that one of the most important factors in the magazine's demise was the decision by the Steins to exploit their position as owners, publisher, and editor of a book-review periodical, a government-subsidized one at that, to publish their own lengthy pre-trial defense of Conrad Black. The chapter then zooms back from the particular to the general with a broader consideration of the impact of technology and globalization on the book industry and on the ability of Books in Canada to survive in any form, print or digital.

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Résumé : La maladie osseuse de Paget (MP) est un désordre squelettique caractérisé par une augmentation focale et désorganisée du remodelage osseux. Les ostéoclastes (OCs) de MP sont plus larges, actifs et nombreux, en plus d’être résistants à l’apoptose. Même si la cause précise de la MP demeure inconnue, des mutations du gène SQSTM1, codant pour la protéine p62, ont été décrites dans une proportion importante de patients avec MP. Parmi ces mutations, la substitution P392L est la plus fréquente, et la surexpression de p62P392L dans les OCs génère un phénotype pagétique partiel. La protéine p62 est impliquée dans de multiples processus, allant du contrôle de la signalisation NF-κB à l’autophagie. Dans les OCs humains, un complexe multiprotéique composé de p62 et des kinases PKCζ et PDK1 est formé en réponse à une stimulation par Receptor Activator of Nuclear factor Kappa-B Ligand (RANKL), principale cytokine impliquée dans la formation et l'activation des OCs. Nous avons démontré que PKCζ est impliquée dans l’activation de NF-κB induite par RANKL dans les OCs, et dans son activation constitutive en présence de p62P392L. Nous avons également observé une augmentation de phosphorylation de Ser536 de p65 par PKCζ, qui est indépendante d’IκB et qui pourrait représenter une voie alternative d'activation de NF-κB en présence de la mutation de p62. Nous avons démontré que les niveaux de phosphorylation des régulateurs de survie ERK et Akt sont augmentés dans les OCs MP, et réduits suite à l'inhibition de PDK1. La phosphorylation des substrats de mTOR, 4EBP1 et la protéine régulatrice Raptor, a été évaluée, et une augmentation des deux a été observée dans les OCs pagétiques, et est régulée par l'inhibition de PDK1. Également, l'augmentation des niveaux de base de LC3II (associée aux structures autophagiques) observée dans les OCs pagétiques a été associée à un défaut de dégradation des autophagosomes, indépendante de la mutation p62P392L. Il existe aussi une réduction de sensibilité à l’induction de l'autophagie dépendante de PDK1. De plus, l’inhibition de PDK1 induit l’apoptose autant dans les OCs contrôles que pagétiques, et mène à une réduction significative de la résorption osseuse. La signalisation PDK1/Akt pourrait donc représenter un point de contrôle important dans l’activation des OCs pagétiques. Ces résultats démontrent l’importance de plusieurs kinases associées à p62 dans la sur-activation des OCs pagétiques, dont la signalisation converge vers une augmentation de leur survie et de leur fonction de résorption, et affecte également le processus autophagique.