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    SINGLE NUCLEOTIDE POLYMORPHISMS AND MICRORNAS AFFECTING PTX3 PRODUCTION

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    Pentraxins are fluid phase pattern recognition receptors phylogenetically conserved from arachnids to mammals. Based on the primary structure, pentraxins are divided in short pentraxins, like the C-reactive protein and the serum amyloid P, and long pentraxins, like PTX3. PTX3 is expressed by several cell types, including mononuclear phagocytes, myeloid dendritic cells, fibroblasts, smooth muscle cells and endothelial cells in response to pro-inflammatory cytokines and microbial components. This molecule is involved in innate immunity, tissue remodelling, female fertility and in tuning the inflammatory response. In particular, PTX3 plays a protective role in cardiovascular diseases (CVD), such as acute myocardial infarction (AMI) and atherosclerosis, in preclinical studies. Moreover, PTX3 has emerged as novel diagnostic and prognostic biomarker in CVD, reflecting the inflammatory involvement of the vascular bed. In AMI patients, PTX3 levels peak 6-8 hours after the onset of symptoms and in this context it balances pro-inflammatory and antiinflammatory stimuli. Since single nucleotide polymorphisms (SNPs) and microRNAs represent two ways in which gene expression can be modified/regulated, we addressed their role in the modulation of PTX3 expression. Given that PTX3 gene SNPs have been reported to be associated to different clinical conditions, in particular in innate resistance to infections, we assessed the role of PTX3 SNPs in affecting PTX3 plasma levels and CVD susceptibility. Despite the characterized role of PTX3 in inflammation, a regulation of PTX3 by microRNAs, which are fundamental fine-tuners of this process, has not yet been described. Therefore, we investigated the role of microRNAs in regulating PTX3 expression. To our first aim, we performed a candidate-gene association study on Caucasian subjects, in about 1500 healthy individuals and 1700 AMI patients. PTX3 plasma levels were measured by ELISA in healthy subjects as well as in AMI patients from GISSI-Prevenzione trial. Blood was collected from AMI patients at least 5 days after the last event. A significant difference in PTX3 levels was detected between AMI patients and controls, suggesting the persistence of high PTX3 plasma levels in AMI patients up to three months after the last event. Moreover, in AMI patients, PTX3 plasma levels significantly correlated with mortality, but not with cardiovascular death or reinfarction, confirming the prognostic value of this parameter previously described as an independent predictor of 3-months mortality in this pathological condition. Moreover, we report that the 3 PTX3 SNPs analysed (the intronic rs2305619 and rs1840680 and the exonic rs3816527), alone or combined in haplotypes, are associated with different PTX3 plasma levels. However, we did not find a correlation between the 3 SNPs analysed and the clinical condition of the subject. About our second aim, data reported in this thesis reveal the existence of a complex network of microRNAs able to down-regulate the basal as well as the TNFα- and IL-1β-induced PTX3 production. The effect of microRNA over-expression was evaluated through the transfection of synthetic pre-miR in the human 8387 fibrosarcoma cell line, able to produce constitutively PTX3. The direct interaction miRNA:mRNA was evaluated through a luciferase reporter assay. Our results reveal that specific microRNAs, like miR-9 and miR-29, directly target and regulate PTX3 mRNA. Other microRNAs, including miR-29, impair PTX3 expression acting on molecules of the signalling pathway that leads to PTX3 transcription. Among these miRNAs there are also miR-146a and miR-155, two of the major microRNAs involved in controlling the inflammatory response. Another microRNA, miR-181c, impairs PTX3 production by targeting key molecules involved in PTX3 induction and by directly acting on the messenger of ERp18, a molecule involved in PTX3 folding. In conclusion, our results underline the complexity of PTX3 regulation, revealing that both PTX3 SNPs and microRNAs are fundamental players of this process

    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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