1,720,954 research outputs found

    Understanding ovarian cancer and chemoresistance through chromosome spatial organisation and nuclear motors

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    This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.20% of patients diagnosed with ovarian cancer (OC) cannot receive treatment at all due to the severity of the disease when discovered. The 80% of patients that receive treatment, as much as, 90% relapse in less than six months and, by the end of two years fail to respond to treatment as a result of multi-drug resistance. As genetic studies fail to provide a complete picture in the biology of disease, epigenetics including spatial and radial organisation of the genome has become a well established that provides a greater understanding beyond the sequence. Chromosomes are non randomly organised within interphase nuclei, which can vary slightly from cell type to cell type, their proliferation and disease status. The functional organisation within interphase nuclei is kept in place and regulated by a plethora of structural and mechanical proteins such as lamins and nuclear myosins (NMs), and along with many other proteins are known together as the nucleoskeleton. Irregularities in these proteins have been implicated in many diseases, including metastatic cancers and their chemoresistant counterparts. NM1 role in spatial chromosome organisation has been established, and with the emergence of NM6 role in nuclear organisation, both their overexpression in OC and involvement transcription presents them as an attractive co-study. This research investigates the disease-related chromosome territory (CT) positionings of OC through four key chromosomes in a panel of OC cells; SKOV-3 PEO-1 PEO-4 MDAH-2774, in addition to a control control cell line HOSEpi. Internally located CT were observed for chromosomes 1, 13 and 17 and a peripheral localisation was observed chromosome X. Chromosomes were subsequently assessed for location post-NM1/6 knockdown revealing that chromosome territories relocalised closer to the localisations of the control cell line, and following the acquisition of platinum-resistance of MDAH-2774, all four chromosomes predominated centrally in nuclei. The analysis also revealed that chromosome X might play a more fundamental role in ovarian tissue and cancer that than previously thought and the initial aim of its use as a control was challenged. Distribution discrepancies in the OC cells were found in the nuclear lamins and myosins with further investigations revealing significant elevations of NM1 and NM6. The elevations also displayed a different stoichiometry ratio in the platinum-resistant cell line PEO-4 which led to the creation of a novel lab-grade platinum-resistant cell line MDAH-2774CR from the naïve line MDAH-2774 to investigate further resistant-specific NM1/NM6 stoichiometry and spatial CT organisation in OC. Moreover, combination assays with MDAH-2774CR and NM1 knockdown resulted in cell death that surpassed its sensitive counterpart, that has future clinical potential to treat chemoresistant OC. In this research, we aim to broaden the comprehension of the many mechanisms involved in the development and progression of an aggressive cancer. The analysis of the CT positioning of 4 out of 23 chromosomes was able to reveal characteristics within OC nuclei at key milestones of the disease, making this level of investigation, and information, important in understanding OC and its successful treatment

    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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