1,720,956 research outputs found
The impact of genotype on the cellular architecture of dilated and arrhythmogenic cardiomyopathies
Get PDFHerzinsuffizienz ist ein klinisches Syndrom, welches durch funktionelle und strukturelle Anomalien des Herzens verursacht wird, und ist weltweit die häufigste Todesursache. Die dilatative Kardiomyopathie, welche durch eine Vergrößerung der linken Herzkammer definiert ist, und die arrhythmogene Kardiomyopathie, welche im Gegensatz durch eine Dysfunktion der rechten Herzkammer definiert ist, sind eine der häufigsten Ursachen für Herzinsuffizienz. Trotz vieler Bemühungen die molekularen Veränderungen der Herzinsuffizienz zu charakterisieren, sind Zelltypzusammensetzung, Genexpressionsänderungen, und zelluläre Interaktionen unter pathologischen Bedingungen unbekannt. Um diese Fragen zu adressieren wurde ein Protokoll zur Isolation intakter Zellkerne entwickelt um Einzelkernsequenzierung im Herzen durchzuführen. Anschließend wurde mit dem entwickelten Protokoll die zelluläre Zusammensetzung des erwachsenen gesunden menschlichen Herzens charakterisiert. Hier war mein Fokus die Charakterisierung und Identifikation von Subformen von Fibroblasten, und deren Genexpressionsunterschiede in den linken und rechten Vorhöfen und Herzkammern. Basierend auf dieser Annotation wurden die Zelltypen und Subtypen von ungefähr 900.000 Zellkernen von 61 nicht-ischämischen Herzinsuffizienzpatienten mit unterschliedlichen pathogenen Varianten in DCM- und ACM-assoziierten Genen oder idiopathischen Erkrankungen charakterisiert und mit 18 gesunden Spenderherzen verglichen. Dieser Datensatz zeigte spezifische Unterschiede des linken und rechten Ventrikels mit differenziell regulierten Genen und Signalwegen, and Veränderungen in der Zusammensetzung der verschiedenen Zelltypen und Subtypen. Um genotyp-spezifische Antworten unabhängig zu bestätigen wurden Algorithmen des maschinellen Lernens angewendet, welche die zugehörige Genotyp-Untergruppe des Patienten mit hoher Genauigkeit vorhersagten. Zusammenfassend stellen die in dieser Arbeit veröffentlichten Daten das vorherrschende Dogma in Frage, dass Herzinsuffizienz auf einen gemeinsamen finalen Signalweg zurückzuführen ist.Heart failure is a clinical syndrom and leading cause of death worldwide, caused by functional and structural abnormalities of the heart. Dilated Cardiomyopathy, defined by a left ventricular enlargement, and arrhythmogenic cardiomyopathy, defined by a right ventricular dysfunction, are leading causes of heart failure. Despite previous efforts to characterise molecular changes in the failing heart, little is known on cell-type specific abundance and expression changes under pathological conditions, and how individual cell-types interact during heart failure and cardiac remodelling.
To address this question, a protocol for the isolation of intact nuclei was firstly established to perform robust single-nucleus RNA sequencing in the heart. Next, the cell-type composition of the healthy adult human heart was characterised. Here my focus was on the fibroblast nieche by characterising fibroblast states, their composition and their atria- and ventricle-specific expression patterns. Cell type and state annotation was then used to characterize the transcriptome of roughly 900,000 nuclei from 61 failing, non-ischemic human hearts with distinct pathogenic variants in DCM and ACM genes or idiopathic disease and compared those to 18 healthy donor hearts. This dataset revealed distinct responses of the right and left ventricle with differently regulated genes and pathways, and compositional changes across cell types and states. To independently confirm genotype-specific responses, machine learning approaches were applied, predicting genotype subgroups with high accuracy. Taken together, the findings published in this thesis upend the prevalent dogma that heart failure results in a final common pathway
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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