1,720,969 research outputs found
WNK1 and its role in hypertension
Get PDFPhDWNK1 is a serine-threonine protein kinase involved in blood pressure (BP) control and electrolyte homeostasis. Intronic deletions in the WNK1 gene result in over-expression and lead to pseudohypoaldosteronism type II, a disorder characterized by hypertension and hyperkalemia. We have previously reported association between WNK1 polymorphisms and BP (associated SNPs map to promoter and intron 1). This PhD investigated whether the associated variants in WNK1 affect gene expression and also explored the role of low frequency haplotypes and copy number variation (CNV) in WNK1 with blood pressure phenotypes.
Bioinformatic analysis was performed to identify conserved regions across species for intron 1 sequence and to test for the presence of any transcriptional factor binding sites (TFBS). Analysis revealed five conserved regions in intron 1 and many putative TFBS, two of these regions, Int1.8 and Int1.9 were tested for functionality using a dual-luciferase assay. Analyses revealed the Int1.8 region to have a 1.33 fold increase (p = 0.002) and Int1.9 a 0.73 fold decrease (p = 0.04) in luciferase expression in HEK293 cells, and results were consistent in the MDCK cells. Bioinformatic analysis performed on BP associated SNPs (rs1468326, rs3088353, rs2107612 and rs765250) revealed a number of TFBS present. One SNP, rs1468326 was tested for functionality using a dual luciferase assay. Analysis revealed allele A to have a 2.5 fold increase in relative luciferase activity compared to allele C (p = 4.8 x 10-11) in HEK293 cells, results were consistent in MDCK cells. To determine if there were proteins binding to rs1468326 sequence an electrophoretic mobility shift assay (EMSA) was performed, followed by LC-MS/MS for protein identification. The data revealed a protein binding to both alleles in HEK293 and MDCK cells but protein identification was not successful due to high non-specific binding. An EMSA experiment for rs3088353 was also performed and an unknown protein was found to bind to both alleles in HEK293 and MDCK cells.
Real-time quantitative PCR (Q-PCR) analysis was performed on mRNA from sixty human kidney tissues to test if 4 BP associated SNPs correlate with WNK1 expression. No significant difference in expression was observed for any of the SNPs tested.
Finally 24 tSNPs were genotyped in 3 case/control resources to try and validate the association of low frequency haplotypes in WNK1 with decreased risk of hypertension. Analyses revealed no association between haplotypes of WNK1 and hypertension. The role of WNK1 CNV and hypertension was also explored using Q-PCR analysis and access to large collaboration studies. No association with CNV in WNK1 was found with hypertension in either WTCCC or GBPG study.
In conclusion, the functional studies performed on WNK1 variants suggest 2 SNPs are potentially functional, but further work will be required to identify the binding proteins. Genetic studies found no evidence for CNV or confirmation of low frequency haplotypes in WNK1 associated with BP phenotypes. The data in this thesis and larger GWAS recently published suggest common variants in WNK1 are not associated with BP, but the data thus far does not rule out the possibility of rare variants affecting BP at this locus
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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