1,721,015 research outputs found

    Investigating a role for activity-regulated cytoskeleton-associated protein in the mast cell response to hydrogen peroxide and rhinovirus infection

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    Mast cells (MCs) are immune cells associated with mucosal surfaces where they are known as allergic and inflammatory effector cells. There is increased MC localisation to the airway epithelium of people with asthma, making them ideally located to respond to inhaled challenges that can trigger asthma exacerbations. A key example is rhinovirus (RV) infection, which is a major exacerbator of asthma. MCs are the only immune cell to support RV replication and release, and RV is the only respiratory virus known to replicate in MCs, but there is limited research showing the implications of this on RV-induced asthma exacerbations. Similarly, there is increased oxidative stress at the airway of people with asthma but the MC response to this oxidative stress is poorly understood. Activity-regulated cytoskeleton-associated protein (ARC) has a well-defined role in neuronal activity, but there is little research about a role for ARC outside of the brain. However, ARC is induced by oxidative stress and negatively regulates the heat shock response in HeLa cells, and ARC is associated with the neuronal and MC response to herpes simplex virus (HSV-1) and RV infection respectively. Therefore, ARC is a protein of interest in the investigation of the MC response to environmental challenges and I hypothesise that ARC plays a functional role in the MC response to both oxidative stress (H2O2 treatment) and RV infection.LAD2 MCs and HeLa cells were treated with H2O2 (2 mM, 1h treatment, 3h or 9h recovery respectively) or infected with RV16 (MOI 1) or a UV-irradiated control prior to quantification of ARC gene and protein expression by RT-qPCR and western blotting. Samples from H2O2-treated and RV16-infected LAD2 MCs were sequenced, and a transcriptomic analysis was used to explore the global response of MCs to these stimuli. Additionally, stable plasmid transfection was used to overexpress ARC in HeLa cells prior to RV infection or H2O2 exposure, using ARC-overexpressing HeLa cells as an initial model to investigate a role for ARC by transcriptomic analysis.To begin, conditions for H2O2 treatment and RV16 infection were optimised, and these data showed that ARC was induced by H2O2 treatment and RV16 infection of both LAD2 MCs and HeLa cells. Next, a HeLa cell line with stable ARC overexpression was produced and samples were generated for RNA-sequencing and subsequent investigation of a role for ARC in the cellular response to H2O2 and RV16. Transcriptomic data did not clearly indicate a role for ARC in the HeLa cells response to H2O2 treatment or RV16 infection, showing that future investigation of a role for ARC in MCs will require the use a MC model with altered ARC expression to gain further information. Transcriptomic analysis showed that H2O2 treatment upregulated the heat shock response and unfolded protein response in MCs, while ubiquitin proteasome system-mediated degradation was downregulated. This suggested that MCs favour protein refolding and autophagic degradation in their response to oxidative stress, contrasting the proteasomal degradation and upregulated the production of antioxidant systems that were associated with H2O2 treatment of HeLa cells. Transcriptomic data from RV16-infected MCs supported the hypothesis that RV is released from MCs via a non-lytic mechanism, in which RV assembly and maturation occurs at Golgi apparatus-derived membranes. Meanwhile, there was no enrichment of vesicle or Golgi apparatus-related pathways in RV16-infected HeLa cells where RV16 release is thought to occur by cell lysis. During this project, I generated datasets which provided transcriptomic profiles of the MC response to both H2O2 treatment and RV16 infection. These give novel information about changes in mediator expression, metabolic pathways and general pathways associated with MC responses that can be further investigated in the future to understand how MCs contribute to oxidative stress- or RV16-induced inflammation in the asthmatic airway. Although these data did not elucidate a role for ARC in the cellular response to stimuli, a set of genes were identified that may be expressed downstream of ARC which could link to the role of ARC in non-neuronal cells. <br/

    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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