1,720,974 research outputs found

    SRC FAMILY KINASE MEMBERS MEDIATE TYPE I INTERFERON PRODUCTION BY PLASMACYTOID DENDRITIC CELLS

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    Plasmacytoid dendritic cells (pDCs) are the most powerful type I interferon (IFN-I) producing cells, playing important roles in defense against pathogens, tumor immune-surveillance and autoimmune diseases. Therefore, understanding pDC regulatory pathways to ultimately manipulate them holds great promise for immune-based therapeutics to attenuate several human illnesses. Here we investigated the role of Src Family Kinases (SFKs), a family of non-receptor tyrosine kinases, in pDC response to toll like receptor (TLR) stimulation. We observed for the first time that pDCs from either Fyn or Lyn deficient mice exhibited impaired IFN-I and pro-inflammatory cytokine production after TLR7 and TLR9 stimulation, whereas no difference was observed in conventional DCs. Consistently, treatment with either a pan-SFK inhibitor or a selective dual BCR-ABL/LYN inhibitor (i.e. Bafetinib) profoundly ablated TLR-induced IFN-I production in both a human pDC cell line (CAL-1) and in primary pDCs from human peripheral blood. Furthermore, genetic ablation of LYN by CRISPR/Cas9 in CAL-1 cells resulted in diminished TLR responses. Mechanistically, we showed that the inhibition of SFK activity by Bafetinib reduced the TLR-induced activation of IKKα/β, ERK1/2, P38 and IRF7, key elements downstream pDC TLR signaling, as well as those of MTOR and BCAP, an adaptor protein that bridges PI3K and TLR pathways. Taken together, our data indicate that SFKs, particularly LYN, promote pDC IFN-I and pro-inflammatory cytokine production and suggest that SFK inhibitory drugs, such as Bafetinib, could be considered for attenuating pDC response in autoimmune diseases

    La cultura tra rinnovamento urbano e globalizzazione. Città e Università: il contributo dell’Alma Mater

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    La città si presenta per tradizione un mileu privilegiato, dove si concentrano trasformazioni politiche, economiche e sociali, perchè è il luogo propizio alla cultura: le vicende passate e attuali lo dimostrano ampiamente. Il sistema urbano europeo lo testimonia ancora di più: esso può essere considerato l'atomo costitutivo della civiltà europea. Il Rimaascimento nasce e si basa sulla cultura e si forma sulle città: è dal XII secolo che nasce l'istituto dell'Università e si forgia la cultura rinascimentale. La storia di Bologna e del suo Studium costituiscono un modello esemplare che ancora oggi si ripropone fondamentale per un secondo Rinascimento urbano

    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
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