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Engineering of bacterial exotoxin and endotoxin antagonists
Get PDFLimited Restriction Lifted for Item 89522 on 2017-09-30T09:15:35Z.Embargo set by: Seth Robbins for item 89522
Lift date: 2017-09-29T21:08:35Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD systemGram negative and positive bacteria have evolved toxins to aid in their ability to colonize host organisms. Some gram-positive bacteria produce exotoxins called superantigens that hyper-stimulate the immune system by crosslinking the variable region of the beta chain (Vβ) of T cell receptors with the antigen presenting major histocompatibility complex II molecule on the surface of antigen presenting cells. This hyper-stimulation leads to overproduction of cytokines, which can result in toxic shock. In addition, the action of the superantigens has been implicated in many diseases including necrotizing pneumonia and endocarditis. Gram-negative bacteria produce lipopolysaccharide (LPS), also called endotoxin, as a major constituent in their outer cell walls. LPS binds to the host protein called MD-2 and the LPS:MD-2 complex associates with cell surface homodimeric Toll-like receptor 4 (TLR4). This tri-molecular interaction can lead to massive stimulation of cytokines from TLR4+ antigen presenting cells, resulting in endotoxic-mediated septic shock. This process has also been suggested to play a role in asthma. A lack of therapeutics for both exotoxin and endotoxin induced shock and implicated diseases, as well as an interest in further understanding these molecular interactions, guided my studies and development of high affinity agents to neutralize these toxins.
In chapter two, directed evolution was used to engineer a high affinity antagonist against the superantigen Staphylococcal enterotoxin C3 (SEC3). I used a previously error-prone engineered Vβ against SEC3 as a starting template for further engineering. Yeast display was used to create two libraries in two different regions of the previously engineered Vβ to improve its affinity for SEC3. The mutations from the highest affinity mutant selected from each library were combined to create a single mutant that had improved binding to SEC3 over either mutant. The highest affinity Vβ antagonist was tested and found to be effective in various rabbit models with SEC3 by the Schlievert laboratory.
Chapter three describes the cross reactivity of the high affinity SEC3 antagonist described in chapter two, with allelic variants of SEC3 (SEC1, SEC2, and SEC4), as well as the highly homologous superantigen, Staphylococcal enterotoxin B (SEB). Residues potentially responsible for the cross reactivity with SEB were mutated and tested for binding to SEB and SEC3. The SEC4 secreting bacteria strain MW2 was used in necrotizing pneumonia and infective endocarditis rabbit models by the Schlievert laboratory that confirmed the in vivo ability of the antagonist to effectively neutralize more than one strain of SEC.
In chapter four, MD-2 was expressed on the surface of yeast and shown to bind MD-2 specific monoclonal antibodies and to its ligands, LPS and TLR4. To test the platform, alanine mutants were engineered at residues identified from previous studies that tested for binding to LPS as well as TLR4. The alanine mutants behaved as anticipated based on the previously published literature. Based on the alanine mutant results, six yeast display libraries were engineered in MD-2 in these regions, and a seventh library was made using error-prone PCR. Ligand studies of the MD-2 mutants allowed identification and insight into the role of critical residues in MD-2 stability and ligand binding.Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2017-08-01The student, Daiva Mattis, accepted the attached license on 2015-05-12 at 09:42.The student, Daiva Mattis, submitted this Dissertation for approval on 2015-05-12 at 09:59.This Dissertation was approved for publication on 2015-05-14 at 09:48.DSpace SAF Submission Ingestion Package generated from Vireo submission #8243 on 2015-09-29 at 15:05:00Made available in DSpace on 2015-09-29T21:02:43Z (GMT). No. of bitstreams: 2
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Previous issue date: 2015-05-14Embargo set by: Seth Robbins for item 89522
Lift date: 2017-09-29T21:03:28Z
Reason: Author requested closed access (OA after 2yrs) in Vireo ETD syste
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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