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Dysregulated activation of immune-inflammatory responses contributes to vascular damage in atherosclerosis and hypertension
No full textAtherosclerosis and hypertension (HTN) are major contributors to the development and progression of cardiovascular disease (CVD). The underlying pathophysiology of atherosclerosis and HTN is similar in that both affect the structural and functional properties of the vasculature as a result of enhanced immune-inflammatory processes in the vascular wall. Vasoactive peptides such as angiotensin (Ang) II and endothelin (ET)-1 can contribute to vascular inflammatory responses and damage, and have been implicated in the progression of both atherosclerosis and HTN. We hypothesize that dysregulated activation of immune-inflammatory mechanisms by vasoactive peptides contributes to the progression of vascular damage in atherosclerosis and HTN.The objectives of this thesis were 1) to determine the role of ET-1-mediated vascular immune-inflammatory mechanisms in progression of hyperlipidemia-induced atherosclerosis and formation of abdominal aortic aneurysms (AAA), 2) to investigate the contribution of pro-inflammatory ET-1 signaling to small artery dysfunction in hyperlipidemia-induced atherosclerosis, and 3) to study the role of anti-inflammatory T regulatory lymphocytes on vascular immune-inflammatory responses in Ang II-induced HTN.The first study shows that endothelium-specific ET-1 overexpression in atherosclerotic apolipoprotein E knockout (Apoe-/-) mice fed a high fat diet exaggerates development of aortic atherosclerotic plaques and triggers formation of AAA. This is accompanied by increase in aortic immune-inflammatory responses, spleen pro-inflammatory monocytes, and expression of matrix metalloproteinase-2 in atherosclerotic plaques. This study also suggests that the suppressive capacity of T regulatory lymphocytes may be reduced during atherosclerosis progression.The second study shows that ET-1 overexpression in high fat diet-fed atherosclerotic Apoe-/- mice results in remodeling of endothelial signaling pathways and potassium channels mediating endothelium-dependent relaxation. Although this remodeling manifests as compensatory preservation of endothelial function, it may in fact represent loss of regulation of endothelium-dependent relaxation in resistance arteries.The third study demonstrates that absence of T regulatory lymphocytes exaggerates microvascular damage in Ang II-induced HTN. The findings of this study show that T regulatory lymphocytes exert vascular protection in part by controlling innate and adaptive immune responses.To conclude, chronic low-grade vascular inflammation in atherosclerosis and HTN involves vasoactive peptide-mediated dysregulation of pro-inflammatory and anti-inflammatory mechanisms in favor of the former. Targeting immune-inflammatory mechanisms may allow us to limit the progression of atherosclerosis and HTN, and therefore the development of CVD.L'athérosclérose et l'hypertension (HTN) sont les causes majeures du développement ainsi que l'aggravation des maladies cardio-vasculaires. Les causes de ses maladies sont similaires dans les deux cas, une altération de la structure et de la fonction des vaisseaux induites par une inflammation dans la paroi de ceux-ci. Les peptides vaso-actifs tels que l'angiotensine (Ang) II et l'endotheline (ET)-1 participent aux réponses inflammatoires et aux dommages que subissent les vaisseaux, et sont impliqués dans la progression de l'athérosclérose et de l'hypertension. Nous supposons que cette dysfonction inflammatoire par les peptides vaso-actifs contribue aux dommages vasculaires liés à l'athérosclérose et à l'hypertension.Les objectifs de cette thèse sont 1) de déterminer le rôle inflammatoire d’ET-1 dans les mécanismes de progression de l'hyperlipidémie induisant l'athérosclérose et dans la formation des anévrismes de l’aorte abdominale (AAA), 2) d’étudier la contribution pro-inflammatoire d’ET-1 dans la dysfonction endothéliale des artères de résistances dans l'athérosclérose induite par l’hyperlipidémie 3) d’évaluer le rôle des lymphocytes T régulateurs anti-inflammatoires sur les réponses immunitaires vasculaires T dépendantes dans HTN induite par l’Ang II.La première étude montre, dans un modèle murin de surexpression d’ET-1 endothélium-spécifique, sur des souris n’exprimant pas l’apolipoprotéine E (ApoE -/-) et nourris avec un régime riche en graisses, une exagération des plaques d'athérome aortique favorisant la formation des AAA. Ceci s’accompagne d'une augmentation de la réponse inflammatoire dans l'aorte, et d’une augmentation des monocytes pro-inflammatoires dans la rate. L’ensemble de ces mécanismes sont liés à la métalloprotéinase 2 dans les plaques d'athérome. Cette étude suggère également que la capacité suppressive des lymphocytes T régulateurs peut être réduite au cours de l'athérosclérose.La deuxième étude montre, dans le même modèle, une altération des voies de signalisation des canaux potassiques favorisant la relaxation endothélium. Cependant, elle se manifeste par un remodelage compensatoire afin de préserver la fonction endothéliale dans les artères de résistance.La troisième étude démontre que l'absence de lymphocytes T régulateurs exagère les lésions microvasculaires dans HTN induite par l’AngII. Les résultats de cette étude montrent que les lymphocytes T régulateurs exercent une protection vasculaire en contrôlant les réponses immunitaires innées et adaptatives.Pour conclure, l'inflammation vasculaire chronique à bas bruit, dans l'athérosclérose et HTN, le dérèglement est médié par les peptides vaso-actifs et leurs composantes pro-inflammatoires ce qui altère les mécanismes anti-inflammatoires protecteurs dans ces pathologies. Cibler les mécanismes immunitaires inflammatoires peut nous permettre de limiter la progression de l'athérosclérose et HTN, et donc le développement des maladies cardio-vasculaires
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
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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