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    Motilität von humanen endometrialen Stromazellen : Rolle in der Implantation und Plazentation

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    Für die erfolgreiche Implantation einer humanen Blastozyste und Ausbildung der Plazenta ist die tiefe Invasion der Trophoblastzellen in das Endometrium Grundvoraussetzung. Neuere Studien zeigen, dass dezidualisierte endometriale Stromazellen ebenfalls ein migratorisches Potential besitzen. Hierdurch könnte die Umstrukturierung des Gewebes und die Einnistung der Blastozyste aktiv unterstützt werden. In dieser Arbeit wurde die gerichtete (Chemotaxis) und die ungerichtete (Chemokinese) Migration nicht dezidualisierter und dezidualisierter humaner endometrialer Stromazellen verglichen. Faktoren, welche zum Zeitpunkt der Implantation lokal im uterinen Milieu nachgewiesen worden waren, sowie Trophoblast-Sekretionsprodukte wurden hinsichtlich ihres Einflusses auf die Migration untersucht. Zusätzlich sollten die beteiligten Signaltransduktionen aufgeschlüsselt werden. Es zeigte sich, dass die Dezidualisierung das basale migratorische Potential endometrialer Stromazellen leicht erhöhte. Unter den Chemotaxis auslösenden Faktoren war einzig PDGF-BB in der Lage, auch eine chemokinetische Motilität der endometrialen Stromazellen zu induzieren. Die chemotaktische Antwort auf HB-EGF wurde durch Dezidualisierung der Zellen verstärkt, was mit einer erhöhten Expression seines Rezeptors EGFR korrelierte. Überstandsmedium sowohl von der Trophoblastzelllinie AC-1M88 als auch von primären Chorionzotten-Explantaten löste eine Chemotaxis aus. Anhand einer Proteom-Analyse wurde PDGF-AA als chemotaktisch aktive Komponente der Trophoblast-Überstände identifiziert, wohingegen die Sekretionsprodukte MIF, PLGF, TGF-β1 und VEGF unwirksam waren. PDGF-BB und HB-EGF wurden in den Trophoblast-Überstandsmedien nicht aufgefunden. Inhibitor-Studien zeigten, dass Signalkaskaden unter Beteiligung von PI3K/Akt(Ser473), ERK1/2 und p38 für die Chemotaxis relevant sind, während eine Chemokinese vorrangig von der Aktivierung des PI3K/Akt(Ser473)-Weges abhängig ist. Sowohl Chemotaxis als auch Chemokinese wurden durch Inhibierung der RhoA/ROCK-Signaltransduktion massiv stimuliert. Zusammenfassend könnte folgendes Modell postuliert werden: Vom Trophoblasten ausgehende chemotaktische Signale, unter anderem PDGF-AA, veranlassen die sich in der Nähe des Invasionsortes befindlichen dezidualisierten Stromazellen, sich in Richtung des „Eindringlings“ zu bewegen. In der sich ausbildenden Dezidua führen von verschiedenen Zelltypen produzierte Faktoren, wie HB-EGF und PDGF-BB, zu einer Migration in Richtung lokaler Gradienten, und PDGF-BB stimuliert darüber hinaus die generelle ungerichtete Motilität der endometrialen Stromazellen. Insgesamt unterstützen diese Prozesse den für Implantation und Plazentation erforderlichen Gewebeumbau.Successful implantation of a human blastocyst and formation of the placenta requires deep invasion of the trophoblast into the decidualized endometrium. It is assumed that decidualized tissue forms a passive barrier that limits trophoblast invasion. Recently, it became evident that human endometrial stromal cells also have remarkable motile and invasive capacities, which may facilitate the extensive tissue remodelling associated with implantation and placentation. In the present study, directed migration (chemotaxis) and random migration (chemokinesis) of non-decidualized and decidualized human endometrial stromal cells were characterized. Local factors, present in the uterine environment at the time of implantation, and trophoblast-derived factors were tested for their ability to modulate stromal cell motility. Further, involved signalling pathways were dissected. A modest increase of basal motility was observed in human endometrial stromal cells upon decidualization. Among the factors inducing chemotactic migration, solely PDGF-BB also elicited a chemokinetic response. Chemotaxis towards HB-EGF was increased in decidualized human endometrial stromal cells compared to non-decidualized human endometrial stromal cells, coincident with up-regulation of the HB-EGF receptor EGFR. Chemotaxis of endometrial stromal cells was stimulated by supernatants prepared from the trophoblast cell line AC-1M88 and from first trimester villous explant cultures. Proteome profiling of trophoblast supernatants revealed PDGF-AA as a chemotactic component, whereas other prominent trophoblast secretions, including MIF, PLGF, TGF-β1 and VEGF, were ineffective. PDGF-BB and HB-EGF were not detectable as trophoblast secretory products. By using specific pathway inhibitors, signalling through ERK1/2, PI3K/Akt(Ser473) and p38 were demonstrated to be involved in chemotaxis. Chemokinesis, on the other hand, appeared to depend mainly on activation of the PI3K/Akt(Ser473) pathway. Chemotaxis and chemokinesis were both massively stimulated by inhibition of the RhoA/ROCK signalling cascade. In conclusion, we postulate the following scenario for early human pregnancy: Trophoblast-derived products, including PDGF-AA, induce a chemotactic response in decidualized endometrial stromal cells towards the implanting intruder. Within the developing decidua, various cell populations produce factors like HB-EGF and PDGF-BB, which trigger endometrial stromal cell migration in response to local gradients. PDGF-BB additionally stimulates random endometrial stromal cell motility. In concert, these processes contribute to tissue remodelling at the fetal-maternal interface

    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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    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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