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    Chromatin-Interaktionen in Kardiomyozyten

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    The blueprint of life, the DNA, is packed as chromatin in restricted nuclear space. Despite of the extremely high density, accessibility of the chromatin has to be ensured to guarantee proper gene expression during differentiation, cellular homeostasis and after extracellular stimulation. The chromatin architecture describes the three-dimensional folding of the chromatin within the nucleus. Chromatin is spatially organised in A- and B-compartments, separating active and less dense packed euchromatin respectively inactive and heavily compacted heterochromatin. The focus of this work was to elucidate the chromatin architecture of murine cardiac myocytes during physiological development and in a pathological disease model. By performing the sequencing-based in situ Hi-C-method on FACS-sorted cardiomyocyte nuclei, A- and B-compartments along with other features of the chromatin architecture were detected. For a comprehensive interpretation, several other epigenetic datasets such as histone modifications and DNA-methylation as well as gene expression data were included.This work shows that adult cardiomyocytes (CM) establish cell-type specific A- and B-compartments as compared to pluripotent embryonic stem cells (ES-cells). CM-specific compartments evolve during differentiation of cardiac progenitor cells (embryonic day 9-11) to fetal cardiac myocytes (E 14.5). The results demonstrate that compartments predict which DNA-methylation signature is established. Partially methylated domains are established in preformed B-compartments in cardiac myocytes after differentiation. To clarify the mutual dependencies between compartments and DNA-methylation, chromatin architecture was investigated in cardiac myocytes with cell-type specific deletion of DNA-methyltransferases 3A and 3B. Absence of de novo DNA-methylation leads to changes of DNA-methylation signatures but does not alter the compartmentalisation in cardiac myocytes. Furthermore, complete absence of DNA-methylation in ES-cells does not change chromatin architecture at all.The results of this work reveal that cell-type specific A- and B-compartments evolve largely during very early stages of cardiomyocyte differentiation. These compartments dictate which DNA-methylation signature is established. However, reduction or loss of DNA-methylation does not change chromatin architecture.Die DNA liegt im Verbund mit Histonen als Chromatin sehr stark komprimiert im Zellkern vor. Trotz der hohen Verdichtung gewährleistet eine gezielte Zugänglichkeit den Ablauf von bestimmten Genexpres-sionsprogrammen in der Entwicklung und in der zellulären Homöostase sowie als Reaktion auf extra-zelluläre Stimuli. Die Chromatinarchitektur beschreibt die dreidimensionale Organisation des Chroma-tins im Zellkern. Das Chromatin ist dabei in A- und B-Kompartimente organisiert, welche aktives und weniger dicht gepacktes Euchromatin beziehungsweise inaktives und stark komprimiertes Hete-rochromatin räumlich voneinander trennen. Um die Frage zu klären, wie sich die Chromatinarchitektur von Kardiomyozyten während der physiolo-gischen und pathophysiologischen Entwicklung ausbildet, wurde im Rahmen dieser Arbeit die Chroma-tinarchitektur mit der sequenzierbasierten in situ Hi-C-Methode an durchflusszytometrisch sortierten Maus-Kardiomyozytenzellkernen untersucht. Die so erhaltenen Daten zur räumlichen Chromatinorgani-sation wurden zusammen mit Histonmodifikationen, der DNA-Methylierung und der Genexpression von Kardiomyozyten analysiert.Die Ergebnisse der vorliegenden Arbeit zeigen deutlich, dass in adulten Kardiomyozyten im Vergleich zu pluripotenten embryonalen Stammzellen (ES-Zellen) Kardiomyozyten-spezifische A- und B-Kompartimente existieren. Diese Kardiomyozyten-spezifischen Kompartimente entstehen nach der Differenzierung von kardialen Progenitorzellen (E9-11) zu Kardiomyozyten (E14,5) und enthalten für Kardiomyozyten essentielle Gene. Darüber hinaus konnte gezeigt werden, dass A- und B-Kompartimente die Ausprägung von DNA-Methylierungssignaturen definieren. Partiell methylierte Domänen sind ein Charakteristikum von B-Kompartimenten differenzierter Kardiomyozyten, nicht aber von ES-Zellen. Um den Zusammenhang zwischen DNA-Methylierung und A/B-Kompartimentierung näher zu untersu-chen, wurden die Gene der de novo DNA-Methyltransferasen 3A und 3B (DNMT3A/B) inaktiviert. Inaktivierung der DNMT3A/B-Gene in Kardiomyozyten hatte einen deutlichen Effekt auf DNA-Methylierungsignaturen, nicht aber auf die Ausbildung der A- und B-Kompartimente. Dieses Ergebnis konnte auch in ES-Zellen reproduziert werden, die keine DNA-Methylierung aufweisen. Diese Ergebnisse zeigen, dass die Zelltyp-spezifische Chromatin-Kompartimentierung die Differenzie-rung von Kardiomyozyten begleitet und bereits früh in der embryonalen Entwicklung abgeschlossen ist. Die Bildung der Chromatinarchitektur ist hierbei nicht abhängig von der DNA-Methylierung. Die Etablie-rung von spezifischen DNA-Methylierungssignaturen geschieht innerhalb von bestimmten Komparti-menten der Chromatinarchitektur

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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 Under Sail The Imagination of Jack London, 1893-1902

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    In 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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