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    Indagine sui meccanismi molecolari alla base dell'efficacia terapeutica delle immunoglobuline G umane. Studi su HUVECs (Human Umbilical Vein Endothelial Cells) e su PBMCs (Peripheral Blood Mononuclear cells)

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    Human Immunoglobulins G (IgG) are increasingly used with beneficial effects in the treatment of a variety of immunological disorders. However, despite the wide therapeutic application, the molecular mechanism by which IgG display their effects is not yet fully elucidated. Several, mutually non-exclusive mechanisms have been proposed that for most part regard effects on cells of immunity, their secretion products and specific IgG receptors. Since IgG are administered by intra venous route and circulate in plasma, the possibility was investigated in this work that IgG can exert their effects on endothelial cells. To this aim, HUVECs (human umbilical vein endothelial cells) that show properties of cells of the innate immunity were chosen in the experimental design and effects of various concentrations of human IgG, purified from blood of healthy donors, measured on cell morphology and on the expression of a panel of heat shock proteins (HSPs) and of matrix metalloprotease-9 (MMP-9) at different incubation times. IgG caused a dose- and time-dependent angiogenic-like transformation of HUVECs that peaked at 20 h incubation and appeared to be associated with the expression of new forms of HSP90, HSP70 and MMP-9 induced by the activation of the PI3K/Akt pathway, whereas the MEK-ERK1/2 pathways was apparently not involved. Measurement of the expression and activity of the proteins in the cell medium demonstrated the active secretion of a proteolytically inactive form of MMP-9 that was secreted in complexes with the HSPs and was responsible for the induction of morphological changes in HUVECs, provided that the stimulus triggered by IgG was sufficiently intense and prolonged. Measurements of IgG expression in both cell lysates and media performed by means of Western blotting and ELISA, together with the analysis of the gene expression of IgG showed that IgG were able to induce their own expression and secretion from the cell. The âex-novoâ synthesis of IgG was triggered by IgG even after they were removed from the incubation medium and replaced with fresh medium without IgG. The process involved the new synthesis of FcRn receptor that was also secreted in association with IgG, a result that proved the participation of FcRn in the cycle of absorbance and secretion of IgG. That the effects of IgG were dependent on their internalization in the cell was also confirmed by immunofluorescence experiments in which IgG were always visualized in the cytoplasm in endocytic vesicles distinct from the cell membrane. The same experiments performed in HUVECs were also conducted on peripheral blood mononuclear cells of three healthy subjects. IgG caused changes in the lymphocyte morphology associated with the stimulation of both the synthesis and the active secretion of IgG; these effects were crucially dependent in their entity on the basal condition of the immune system of each subject. Results revealed for the first time the capacity of IgG to induce their own synthesis and secretion in a particular type of endothelial cells physiologically not deputed to these functions. This effect, together with the activation of the immune cells, might be of therapeutic value, since it can enhance and prolong the immune response following the intra venous administration of IgG. The mechanism involved in the "ex-novo" synthesis of IgG appears to be independent of that responsible for the morphological changes of cells that instead requires a more intense and prolonged activating stimulus by IgG

    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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