1,720,953 research outputs found
Editing of the SLURP1 gene in Mal de Meleda (MDM) disease using prime editing technology
No full textMal de Meleda (MDM), kromozom 8q24.3 üzerinde bulunan, epidermal homeostazı ve deri iltihabını düzenleyen, salgılanan memeli Ly-6/ürokinaz tipi plazminojen aktivatör reseptörünü (uPAR) ilişkili protein-1 (SLURP1) proteinini kodlayan SLURP1 genindeki mutasyonlardan kaynaklanan inflamatuar palmoplantar keratodermanın nadir bir formudur. CRISPR-Cas9'un geliştirilmiş bir versiyonu olan Prime editing 2019 yılında tanımlanmış ve hassas baz düzenlemeleri yapabilen etkili bir genom düzenleme teknolojisidir. Bu tezde, SLURP1 geninde c.286C>T mutasyonu olan bireye ait in vitro modelde, Prime editing kullanılarak mutasyonun düzeltilmesi amaçlanmıştır. Çalışma, ilk olarak uygun plazmidler seçilerek, SLURP1 geninde c.286C>T mutasyonuna uygun epegRNA tasarımı yapılarak başlamıştır. Tasarlanan epegRNA oligonükleotidleri, annealing yöntemi ile birleştirilerek mRFP1 bölgesi kesilmiş pU6-tevopreq1-GG-acceptor plazmidine Golden Gate yöntemi ile klonlanmıştır. Klonlanan plazmid, DH5α bakterilerine transformasyon yoluyla aktarılmış ve koloni seçimi sonrası izole edilen plazmid DNA'sı doğrulanmıştır. Hastanın periferik kanından elde edilen lenfosit hücre kültürüne hazırlanan Prime Editor sistemi (nCas9-RT + epegRNA) transfekte edilmiştir. Transfeksiyon verimliliği ve düzenleme etkinliği değerlendirmek üzere hedef bölgeye özgü primerler tasarlanmış, PZR amplifikasyonu sonrası sadece hedef varyanta yönelik olarak sınırlı kapsamlı bir Yeni Nesil Dizileme (NGS) analizi uygulanmıştır. Yapılan her aşama optimizasyon ile güçlendirilmiş ve istenilen sonuç alınana kadar diğer aşamaya geçilmemiştir. NGS sonucunda, FASTQ formatındaki sekans verileri Notepad++ yazılımı kullanılarak analiz edilmiş ve düzenleme oranları hesaplanmıştır. SH1 ve SH2 örneklerinde sırasıyla %0,40 ve %0,23 düzeyinde düzeltme sağlandığı tespit edilmiştir. Görece düşük düzeltme oranlarına rağmen, analizler hedeflenen varyant bölgesinde spesifik bir düzeltmenin başarıyla gerçekleştirildiğini göstermektedir.Mal de Meleda (MDM) is a rare form of inflammatory palmoplantar keratoderma caused by mutations in the SLURP1 gene, which encodes the secreted mammalian Ly-6/urokinase-type plasminogen activator receptor (uPAR)-related protein-1 (SLURP1) protein located on chromosome 8q24.3, which regulates epidermal homeostasis and skin inflammation. Prime editing, an improved version of CRISPR-Cas9, was described in 2019 and is an effective genome editing technology that can perform precise base editing. In this thesis, we aimed to correct the mutation using Prime editing in an in vitro model belonging to an individual with a c.286C>T mutation in the SLURP1 gene. The study was started by selecting suitable plasmids and designing epegRNA suitable for the c.286C>T mutation in the SLURP1 gene. The designed epegRNA oligonucleotides were annealed and cloned into the pU6-tevopreq1-GG-acceptor plasmid with a truncated mRFP1 region using the Golden Gate method. The cloned plasmid was transferred to DH5α bacteria via transformation and the isolated plasmid DNA was verified after colony selection. The Prime Editor system (nCas9-RT + epegRNA) prepared for lymphocyte cell culture obtained from the patient's peripheral blood was transfected. In order to evaluate the transfection effıciency and editing effıciency, target region-specific primers were designed and a limited-scope Next Generation Sequencing (NGS) analysis was applied only for the target variant after PCR amplification. Each stage was strengthened with optimization and the next stage was not passed until the desired result was obtained. As a result of NGS, sequence data in FASTQ format were analyzed using Notepad++ software and editing rates were calculated. It was determined that corrections were achieved at 0.40% and 0.23% levels in SH1 and SH2 samples, respectively. Despite the relatively low correction rates, the analyses show that a specific correction was successfully achieved in the targeted variant region.Bu araştırma Selçuk Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü tarafından 24202008 Proje numarası ile desteklenmiştir
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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