1,720,971 research outputs found
Alteration of the Epithelial Environment and Cellular Pathways by HPV type 16 E6 and NFX1-123
Get PDFThesis (Ph.D.)--University of Washington, 2018High-risk human papillomaviruses (HR HPV) are the causative agent of various anogenital and oropharyngeal cancers, accounting for approximately 5% of the global burden of cancer. The highest risk factor for development of these cancers is a persistent infection with HR HPV. Understanding what promotes long-lived HPV infection is critical for predicting and preventing serious disease outcomes. Persistent infection with HR HPV requires successful propagation in stratified squamous epithelium and is therefore driven by how HR HPVs manipulate the host cell to create an environment beneficial to the viral life cycle. The study of HR HPV, their interactions with the host cell, and how these interactions engender cellular changes that may secondarily lead to oncogenesis is the focus of this dissertation. This dissertation summarizes several ways in which a HR HPV oncoprotein, HPV type 16 E6 (16E6), partners with a host protein, NFX1-123, to manipulate cellular processes and promote its life cycle. Previous work in the laboratory has shown that 16E6 utilizes NFX1-123 to upregulate differentiation markers in keratinocytes; increase levels of Notch1, the master cell fate regulator; and increase expression of telomerase, an enzyme critical to immortalization. The studies presented here further define the cellular processes altered by 16E6 and NFX1-123 to create a cellular milieu beneficial to the viral life cycle. Evasion of the immune response by HR HPVs has been well-documented, but the many molecular mechanisms and protein partners driving these immune deregulatory functions have not yet been fully defined. The data in Chapter 3 establishes 16E6 and NFX1-123 as one such protein partnership through which HR HPVs interfere with the innate immune response and escape detection within infected epithelial cells. Overexpression of NFX1-123 in 16E6 keratinocytes 1) decreased expression of pro-inflammatory cytokines and interferon-stimulated genes (ISGs) at the mRNA and protein level 2) decreased total levels of TRAF6 and TAB2, two proteins in the signaling cascades that govern induction of these antiviral genes and 3) disturbed the normal localization of these signaling proteins. Initiating the immune response within infected keratinocytes is critical for detection of HPV infection and subsequent clearance; deregulating intracellular immune signaling allows HR HPV to avoid detection and resist immune clearance, a necessity for establishing persistent infection. The HPV life cycle is tied to the differentiation programming of epithelial cells, with cellular differentiation driving initiation of the late stage of life viral cycle. Chapter 4 identifies for the first time a role for NFX1-123 in regulating keratinocyte differentiation and late events of the HPV life cycle. NFX1-123 augmented JNK signaling in 16E6 HFKs undergoing differentiation through expression of upstream kinase regulators of JNK, MKK4 and MKK7. Consistent with the connection between the HPV life cycle and differentiation, modulating levels of NFX1-123 in HPV16-positive W12E cells affected late events of the viral life cycle. Altering levels of NFX1-123 resulted in altered mRNA expression levels of L1, the major capsid protein of HPV. 16E6 and NFX1-123 have previously been shown to target the known oncogenic protein telomerase, increasing expression and activity of its catalytic subunit, hTERT. In Chapter 5, we further explore how 16E6 and NFX1-123 targeting of telomerase affects growth and proliferative potential of cells over long term cell culture. The data presented in this chapter demonstrate that NFX1-123 is highly expressed in primary cervical cancers. In vitro, cells expressing 16E6 and overexpressing NFX1-123 had extended active growth, decreased senescence marker staining, and more rapid cell cycling compared to 16E6 expressing cells with endogenous amounts of NFX1-123. These effects on cell proliferation were associated with increased telomerase activity and expression of its catalytic subunit, hTERT. HPV 16-positive cervical cancer cell lines with knocked down NFX1-123 had slowed growth and reduced hTERT. These data indicate that 16E6 and NFX1-123 not only extend proliferative potential of cells via telomerase, but also modify active cellular growth, augment hTERT expression, and increase telomerase activity over time. Altogether, the work in this dissertation describes multiple epithelial cell pathways that HR HPV type 16 E6 and NFX1-123 modify, which subsequently alter the host cell milieu to potentially promote HPV infection and support oncogenic development
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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