1,721,007 research outputs found
Identifizierung von Individuen mit breit neutralisierender Serumaktivität gegen HIV-1
No full textBroadly neutralizing antibodies (bNAbs) present a promising new option in prevention and therapy of HIV-1 infection. Since the clinical use of bNAbs is limited by viral escape through mutations of the HIV-1 envelope glycoprotein (Env), more bNAbs need to be purified in order to unveil more viral vulnerabilities as well as various pathways of HIV-1 escape. Elite neutralizers have been the source of the second generation bNAbs, so it was the goal to identify these individuals within large cohorts of HIV-1-infected individuals.
In the first part of the study, we screened HIV-1-infected individuals out of two diverse cohorts for broadly neutralizing serum activity. The sera of 294 long-term-non-progressors (LTNP-SELECTED cohort) and 343 subjects mostly treated with ART (UNSELECTED cohort) were tested on the first neutralization assay by Monogram Biosciences (MB) with 5 different HIV–1 subtypes. With the help of a new scoring system, these sera were ranked based on their neutralizing activity. Subsequently, the top 19 LTNP-SELECTED individuals and the top 20 UNSELECTED individuals were chosen for a second screening on an extended neutralization panel with a broader set of HIV-1 isolates. Here, 12 individuals were identified as elite neutralizers making up 1.8% out of total 637 individuals. Our results show that the combination of two neutralization panels and the new ranking system can be used to identify individuals with elite HIV-1 neutralizing activity out of diverse cohorts.
In the second part of this study, the neutralization results of both cohorts were analyzed. A cohort's performance on the MB panel was associated by trend with greater breadth and higher potency on the extended panel. Another observation was that in both cohorts, breadth and potency of the samples correlated significantly on the MB panel but not on the extended panel. The top chosen LTNP-SELECTED and UNSELECTED individuals showed a similar level of neutralizing activity both on the MB and on the extended panel. Furthermore, the analysis of the MB panel revealed a significant correlation between neutralizing activity and the passed years since infection in the LTNP-SELECTED group. Also on the MB panel, no difference of HIV-1 serum neutralization was observed between treated and untreated UNSELECTED individuals.
In the third part, we used mutated variants of gp120 in order to narrow down the epitope specificities of the top 39 neutralizers. 80% of the samples had specificities linked to epitopes in the V1/V2 apex, the V3 loop or the CD4 binding site of the HIV-1 envelope. The specificities of 5-10 % of samples remained undetected.Breit neutralisierende Antikörper (bNAbs) stellen eine vielversprechende neue Option in der Prävention und Therapie einer HIV-1 Infektion dar. Die Selektion viraler Escape-Varianten durch Mutation des Env-Glykoproteinkomplex erschwert jedoch die klinische Anwendung von bNAbs. Daher sollten mehr bNAbs entdeckt werden, um weitere empfindliche Epitope sowie Escape-Mechanismen des HI-Virus zu beschreiben. Effektive bNAbs der zweiten Generation wurden aus Elite Neutralizern gewonnen, dementsprechend war das Ziel dieser Arbeit, Elite Neutralizer aus großen Kohorten von HIV-1-infizierten Individuen zu identifizieren.
Im ersten Teil der Dissertation untersuchten wurden die Seren von 294 Long-term-non-progressors (LTNP-SELECTED Kohorte) und 343 Individuen aus einer größtenteils mit ART behandelten Kohorte (UNSELECTED) auf dem ersten Neutralisationsassay von Monogram Biosciences (MB) mit 5 verschiedenen HIV-1 Subtypen getestet. Mithilfe eines neuen Punktesystems wurden diese Seren in einen Rang eingereiht, welcher die Neutralisationsaktivität berücksichtigte. So wurden die Top 19 LTNP-SELECTED und 20 UNSELECTED Individuen ausgewählt für das zweite Screening auf einem erweiterten Assay mit einem breiteren Set an HIV-1 Isolaten. Hieraus gingen 12 Individuen als Elite Neutralizer hervor und machten 1,8% der zu Beginn 637 eingeschlossenen Personen dieser Studie aus. Unser Ergebnis bestätigt, dass die Kombination aus beiden Neutralisationsassays und unserem Punktesystem geeignet ist, um Elite Neutralizer in unterschiedlichen Kohorten zu finden.
Im zweiten Teil dieser Studie wurden die Neutralisationsergebnisse beider Kohorten analysiert. Die Neutralisationsleistung auf dem MB Assay war tendenziell mit einer höheren Neutralisationsbreite und -potenz auf dem erweiterten Assay vergesellschaftet. Die Analyse der LTNP-SELECTED Kohorte auf dem MB Assay brachte eine signifikante Korrelation zwischen Neutralisationsaktivität und vergangene Jahre nach Infektion hervor. Zwischen den mit ART behandelten und nicht behandelten UNSELECTED Individuen gab es keinen Unterschied in der Neutralisationsaktivität auf dem MB Assay.
Im dritten Teil benutzten wir ein Assay mit mutierten Varianten von gp120, um die Bindungsspezifitäten der Top 39 Individuen aus beiden Kohorten einzugrenzen. 80% der Top Seren waren spezifisch für Epitope im V1/V2 Apex, im V3 Bogen oder an der CD4 Bindungsseite des HIV-1 Hüllenproteins. Die Spezifitäten von 5-10% der Seren konnten nicht detektiert werden
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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