1,720,967 research outputs found
Lipopolysaccharide- and p38 MAPK-mediated signaling of the Heme oxygenase-1 (HO-1) gene in macrophages
Get PDFMonocytes or macrophages are crucial regulators of inflammation. Intracellular signaling in macrophages is tightly regulated to ensure that they do not undergo excessive activation, which may lead to chronic inflammation accompanied with potential damage to the host tissue. Induction of HO-1 in macrophages has been shown to have potent immunomodulatory properties.In this thesis two different signalling mechanisms are described which lead to the induction of HO-1 in macrophages. In the first part the signalling pathway leading to the induction of HO-1 via toll-like receptor (TLR)4 by the classical pro-inflammatory stimulus lipopolysaccharide (LPS) is described. The second part of this thesis deals with the induction of HO-1 caused by the inhibition of the mitogen activated protein kinase (MAPK) p38.Induction of HO-1 by LPS in macrophages has been described earlier, but the exact regulatory mechanisms of this pathway are not well understood. In this thesis it is shown that Bruton s tyrosine kinase (Btk) mediates the LPS-induction of HO-1. LPS-dependent induction of HO-1 was blocked in macrophages treated with the Btk inhibitor, LFM-A13 or in Btk alveolar macrophages. Promoter studies and quantitative real time PCR studies revealed a transcriptional regulatory mechanism. Btk was shown to mediate the production of ROS and activation of the transcription factor Nrf2.p38 MAPK inhibition is shown to increase the expression of HO-1. This was rather surprising, because activation of p38 MAPK has earlier been shown to mediate HO-1 induction caused by various stimuli. This increase in HO-1 expression was also observed in p38mouse embryonic fibroblasts. Further analysis revealed that p38 inhibition leads to an increased production of reactive oxygen species (ROS) and activation of Nrf2. Furthermore, ERK MAPK was also shown to be involved in this pathway.Taken together, this thesis demonstrates that signaling to HO-1 in macrophages is primarily mediated by the transcription factor Nrf2. Further studies to unravel the regulation of this gene may help to develop novel strategies for clinical intervention in inflammatory disorders.Monozyten und Makrophagen spielen eine bedeutsame Rolle für die Regulation von Entzündungsreaktionen. Die intrazelluläre signaltransduktion in Makrophagen wird streng reguliert, um eine überschießende Aktivierung dieser Zellen zu vermeiden, die zu einer chronischen Entzündung mit möglicher Gewebeschädigung führen könnte. Für die Induktion der Hämoxygenase (HO)-1 in Makrophagen konnte eine wirksame immunmodulatorische Wirkung gezeigt werden.In der vorliegenden Arbeit werden zwei verschiedene Signalübertragungwege beschrieben, die zu einer Induktion der HO-1 in Makrophagen führen. Im ersten Teil der Arbeit ist ein Signalweg beschrieben, der zu einer Induktion der HO-1 über eine Aktivierung von Toll-like Rezeptor (TLR)-4 durch den klassischen pro-inflammatorischen Stimulus Lipopolysaccharid (LPS) führt. Der zweite Teil der Arbeit beschäftigt sich mit der Induktion der HO-1 durch die Inhibition der Mitogen-aktivierten Proteinkinase (MAPK) p38.Die Induktion der HO-1 durch LPS wurde bereits früher erstmals beschrieben, aber die genauen regulatorischen Mechanismen sind nicht genau bekannt. In der vorliegenden Arbeit wurde gezeigt, dass die Bruton-Tyrosinkinase (Btk) die LPS-abhängige Induktion der HO-1 vermittelt. Die HO-1 Induktion durch LPS wurde durch Behandlung von Makrophagen mit dem Btk Inhibitor LFM-A13 oder in Btk-/- Alveolarmakrophagen blockiert. Promoterstudien und quantitative real time PCR Studien zeigten einen zugrundeliegenden transkriptionalen Mechanismus.Weiterhin konnte gezeigt werden, dass die Inhibition der p38 MAPK die HO-1 Expression heraufreguliert. Dieser Befund war unerwartet, weil in früheren Untersuchungen gezeigt worden war, dass p38 Aktivierung die Induktion der HO-1 vermittelt hatte. Diese HO-1 Induktion konnte auch in p38-/- murinen embryonalen Fibroblasten beobachtet werden. Weitere Untersuchungen zeigten, dass die Inhibition von p38 zu einer gesteigerten Produktion von reaktiven Sauerstoffspezies (ROS) und einer Aktivierung von Nrf2 führte. Außerdem konnte gezeigt werden, dass die MAPK ERK an dieser Regulation beteiligt war.Zusammenfassend zeigt diese Arbeit, dass die signaltransduktion zum HO-1 Gen in Makrophagen in erster Linie durch den Transkriptionsfaktor Nrf2 vermittelt wird. Weitere Studien zur Aufklärung der genauen Regulation dieses Genes könnten dabei helfen, neue Behandlungsstrategien bei der entzündlichen Erkrankungen zu entwickeln
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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