1,720,953 research outputs found
A Mechano-Molecular Landscape Underlying Regionalized Left Ventricular Fibrosis in Mitral Valve Prolapse
No full textMitral Valve Prolapse (MVP) is a common heart valve condition characterized by superior displacement of one or both mitral valve leaflets during systole and often failure of leaflet coaptation. Although historically thought of as a benign condition, with secondary consequences thought to occur as a result of worsening mitral regurgitation (MR), recent studies have highlighted an association between MVP, regionalized myocardial fibrosis of the subvalvular myocardium, and potentially lethal ventricular tachyarrhythmias including ventricular tachycardia (VT) and ventricular fibrillation (VF). Often, patients who present with life-threatening arrhythmias have a phenotypically “moderate” regurgitation and are not surgical candidates; Yet, other clinically measurable variables suggest these patients present with a mechanically severe form of MVP, characterized by bi-leaflet involvement, abnormal myocardial and annular mechanics during systole, and mitral annular disjunction (MAD). Nonetheless, current AHA/ACC medical and surgical guidelines do not adequately risk stratify MVP patients based on the mechanical severity of their disease. Furthermore, the underlying mechano-molecular interactions that initiate and sustain fibrosis and arrhythmias in MVP are not well understood and represent an unmet clinical need for therapeutics which can slow or reverse mechanically-induced fibrosis. This dissertation reviews the macroscopic and microscopic anatomy of the mitral valve as well as what is known about the clinical causes and consequences of mitral valve prolapse, including ventricular arrhythmias. We further test the hypothesis that mitral valve prolapse induces regionalized left ventricular fibrosis by increasing mechanical stress on the subvalvular myocardium, which in turn activates fibrogenic pathways within cardiac fibroblasts. In aim 1, we demonstrate regionalized myocardial fibrosis occurs in human patients at the time of MV surgery with increases in CD206 expressing macrophages, and a-Smooth Muscle Actin expressing myofibroblasts in valve-linked myocardial regions. We additionally show that induction of MVP using a geneticallyaccurate mouse model of human non-syndromic MVP phenocopies the human findings and causes progressive myocardial fibrosis with time. In aim 2, we develop a non-genetic surgical model of MVP in a large animal which allows us to induce prolapse and the associated mechanical stress with a genetically normal myocardium and test the response of subvalvular myocardium to mechanical stress. We show that surgical induction of MVP causes regionalized fibrosis, consistent with a mechanism of regionalized fibrosis secondary to abnormal valve induced mechanical stress on the subvalvular myocardium. In aim 3, we apply mechanical stress in the form of stiffness to primary human cardiac fibroblasts and perform an integrative, multi- ‘omic’ profiling analysis in order to identify pathways which drive mechanical stress-induced fibrosis. We show that mechanical stress induces broad transcriptional and epigenetic changes consistent with upregulation of fibrogenic pathways. Our results identify the mechanosensitive gene MYH10, which encodes non-muscle myosin IIB, and demonstrate how transcription of MYH10 is epigenetically regulated by mechanical stress through an intronic repressor element which binds the transcription factor JUND. Finally, we highlight potential upstream signaling pathways which may regulate MYH10, including purinergic signaling by Connexin 43 hemichannels. Conclusions from this work are that regionalized fibrosis in MVP is progressive, occurs secondary to the valve defect, and is in part driven by pathways which may be targeted using pharmacotherapeutics. Our work further questions whether earlier surgical intervention in a subset of MVP patients may reduce the risk of lethal ventricular arrhythmias and be of therapeutic value
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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