1,720,955 research outputs found
In Vivo Genotoxicity and Selection Associated with Thiopurine Treatment in Subjects with Inflammatory Bowel Disease
Full text linkThiopurines azathioprine and 6-mercaptopurine are effective immune-modulators and cytotoxic agents widely used in the treatment of autoimmune diseases, graft rejection, and cancer. Of concern is the growing epidemiologic evidence that chronic exposure to these agents increases the risk of mesenchymal and solid tumors. Although in vitro and in vivo animal studies suggest that these agents are mutagenic and have the potential to select for mismatch repair deficient mutants, their in vivo mechanism(s) of carcinogenicity in humans remain(s) unclear. We investigated the in vivo mutagenicity of thiopurines in a cross-sectional study of 119 children and adults with inflammatory bowel disease by determining the frequency and spectra of somatic mutations at the HPRT locus using the T-cell cloning assay. We observed a significant increase in the frequency of somatic mutations that was related to total dose (p<0.001) and duration of treatment (p<0.001) among 56 thiopurine treated subjects compared to 63 untreated subjects. By mutation spectra comparison of 1020 mutant isolates, we also observed a significant dose-dependent increase in the proportion of G:C to A:T transitions (p<0.001) that is consistent with the in vitro mutagenic signature of these drugs. Although in vivo selection for HPRT mutants may have confounded the absolute mutation frequency since this is a ratio value, the significant thiopurine dose-dependent correlations with frequency and mutation spectra shift strongly suggest that thiopurine treatment is mutagenic in vivo. We also investigated the prevalence of in vivo clonal proliferation by the combined analyses of HPRT mutations and TCRβ CDR3 regions from mutant isolates and observed a higher prevalence of cell proliferation in association with chronic thiopurine therapy. Thiopurine treated subjects displayed expansions of precursor or committed progenitor cells and post-β rearrangement thymocytes or mature T-cells while untreated adult subjects showed only post-β rearrangement expansions of thymocytes or mature T-cells. Thiopurine treated subjects also uniquely displayed clonal expansions of “hyper-mutable” thymocytes or mature T-cells that gave rise to progenies with independent mutations either through extensive proliferation or from genetic instability. This pattern predominated in children and exhibited the highest occurrences of G:C to A:T mutations. G:C to A:T transitions were also observed in both early precursors or committed progenitors and post-β rearrangement thymocytes or mature T-cells from thiopurine treated subjects compared to untreated subjects who displayed a low frequency of G:C to A:T mutations unrelated to thiopurine therapy in post-β rearrangement thymocytes or mature T-cells. These data provide direct evidence that thiopurine treatment is mutagenic in vivo by mutation induction that may be enhanced through its effects on cell proliferation, and provide the first mechanistic evidence for the carcinogenicity of these therapeutic agents in humans. Our observations also suggest the potential risks to proliferating precursor and mature cells. In children, we may be capturing a subpopulation of “hypermutable” T-cells with a higher propensity to progress to lymphoma, which occur at highest frequency following transplantation.Cell and Molecular BiologyDoctor of Philosophy (PhD
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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