1,720,954 research outputs found
Determining the impact of macrophage-derived Dnase1L3 in lupus-like phenotypes in mice and its implications for treatment
No full textSystemic Lupus Erythematosus (SLE) is a challenging autoimmune disease with limited treatment options. It arises from a combination of environmental factors and mutations in specific genes, including the Dnase1L3 gene. Dnase1L3, released by myeloid cells into the bloodstream, plays a crucial role in breaking down DNA within apoptotic bodies and chromatin, thereby reducing autoantibody formation and preventing SLE. However, there are several unknowns in the Dnase1L3 field, this project focuses on addressing key challenges in the study of Dnase1L3. Firstly, there is a need for specific activity assays that can differentiate between Dnase1L3 and Dnase1. Additionally, the importance of a minimum threshold concentration of Dnase1L3 activity in disease prevention remains unknown. Moreover, the impact of increasing the size of Dnase1L3 through PEGylation has not been explored in preclinical and serum half-life studies. To shed light on the role of partial Dnase1L3 loss in disease mechanisms, the project aims to utilize lupus murine models. The main objective is to develop functional assays for measuring Dnase1L3 specific activity. Furthermore, the project seeks to assess the effects of macrophage derived Dnase1L3 loss on specific cell types, such as macrophages, using conditional knockout mouse models. Finally, to evaluate Dnase1L3 as a potential therapeutic, the project aims to identify the lead candidate and determine its serum half-life. By addressing these objectives, this research aims to enhance our understanding of Dnase1L3 and its potential implications in disease prevention and treatment. In aim 1 I developed specific activity assays for Dnase1 and Dnase1L3. The plasmid digestion assay proved highly specific for Dnase1, while the immune complex degradation assay reliably measured Dnase1L3 activity. Next, to measure the impact of reduced Dnase1L3 protein levels were investigated through conditional knockout mice lacking Dnase1L3 in macrophages. These mice exhibited reduced serum Dnase1L3 levels, along with lupus-like symptoms such as increased autoantibodies and kidney pathology. The findings suggest that intermediate reduction in serum Dnase1L3 is sufficient to cause mild lupus phenotypes, highlighting Dnase1L3 as a key therapeutic target for lupus. Exploring strategies for enhancing Dnase1L3 enzyme replacement therapy, pegylated Dnase1L3 mutants have been evaluated and shown to have preserved activity. Serum half-life studies in lupus mouse models demonstrated prolonged stability of pegylated Dnase1L3, suggesting that PEGylation could improve the pharmacokinetics and reduce immunogenicity of Dnase1L3 enzyme replacement therapy in SLE. In conclusion, this study sheds light on the role of Dnase1L3 in SLE pathogenesis, the consequences of reduced Dnase1L3 activity, and strategies for enhancing Dnase1L3 enzyme replacement therapy. These findings contribute to a better understanding of the mechanisms underlying SLE and offer potential avenues for targeted treatment in autoimmune diseases
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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