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    AKR1B1 VE AKR1B10 aşırı ifadelenmesinin kolorektal kanser hücre hatları üzerindeki fonksiyonel etkilerinin değerlendirilmesi

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    Aldo-keto reductases (AKRs) are nicotinamide adenine dinucleotide phosphate (NADPH)-dependent enzymes with diverse cellular metabolism functions. AKR1B1 and AKR1B10 are two of the most studied enzymes in the AKR family. AKR1B1 reduces excess glucose into sorbitol using reducing electrons from NADPH, and the hyperactivation of the AKR1B1 pathways is associated with oxidative stress and cell death. AKR1B10 is a poor reductant of glucose but is a vital enzyme that can metabolize retinol and many other drugs and therefore is implicated in cancer development. Our previous research has shown that high expression of AKR1B1 and AKR1B10 in colorectal cancer can have divergent effects. Thus, while high expression of AKR1B1 was associated with a strong epithelial to mesenchymal (EMT) and pro-inflammatory phenotype, high expression of AKR1B10 showed activation of nutrient-sensing pathways. In order to better understand the functional effects and underlying cellular signaling pathways, we overexpressed both enzymes in cell lines RKO and SW480 that do not endogenously express AKR1B1 or AKR1B10. Functional assays showed no significant alterations in cellular proliferation in 2D cell culture, which was also reflected in no alterations in colony formation capacity. AKR1B10 overexpressing cells had a greater vulnerability to serum starvation reflected by a high number of cells arrested in the G1 phase of the cell cycle. AKR1B1 overexpressing cells compared to AKR1B10 overexpressing cells showed significantly higher motility, confirming our previous data. RNA sequencing of AKR1B1 and AKR1B10 overexpressing RKO cells indicated that gene ontology (GO) terms previously established in high AKR1B1 or AKR1B10 expressing tumor samples (that have an expression from both epithelial and stromal compartments) overlapped with the GO terms obtained in RKO cells. Thus, high AKR1B1 overexpressing cells were significantly associated with ROS-related processes, whereas AKR1B10 overexpressing cells were significantly associated with the inhibition of metabolic and biosynthetic processes.Aldo-keto redüktazlar (AKR'ler), çeşitli hücresel metabolizma fonksiyonlarına sahip nikotinamid adenin dinükleotid fosfat (NADPH) bağımlı enzimlerdir. AKR1B1 ve AKR1B10, AKR süperailesinde en çok çalışılan enzimlerden ikisidir. AKR1B1, hücredeki fazla glikozu, NADPH'den gelen indirgeyici elektronları kullanarak sorbitole indirger ve AKR1B1 yolaklarının hiperaktivasyonu, oksidatif stres ve hücre ölümü ile ilişkilidir. AKR1B10, glikozun zayıf bir indirgeyicisi olmasına karşın retinol ve diğer birçok ilacı metabolize edebilen ve bu nedenle kanser gelişiminde rol oynayan hayati bir enzimdir. Önceki araştırmamız, kolorektal kanserde yüksek AKR1B1 ve AKR1B10 ifadelenmesinin farklı etkilere sahip olabileceğini göstermiştir. Yüksek AKR1B1 ifadelenmesi, epitelyal-mezenkimal geçiş (EMT) ve güçlü bir proinflamatuar fenotip ile ilişkilendirilirken, AKR1B10'un yüksek ifadelenmesi, besin algılama yolaklarının aktivasyonunu göstermiştir. Fonksiyonel etkileri ve altta yatan hücresel sinyal yolaklarını daha iyi anlamak için, AKR1B1 veya AKR1B10'u endojen olarak ifade etmeyen RKO ve SW480 hücre hatlarında iki enzimin de aşırı ifadelenmesi sağlanmıştır. Fonksiyonel analizler, 2D hücre kültüründe hücresel proliferasyonda önemli bir değişiklik göstermemiştir ve aynı zamanda koloni oluşturma kapasitesinde bir değişiklik gözlemlenmemesi de bunu doğrulamıştır. AKR1B10 aşırı ifade eden hücrelerde, hücre döngüsünün G1 fazında kalmış yüksek sayıda hücrenin olduğu gözlemlenmiştir, bu da hücrelerin serum açlığına karşı daha fazla savunmasızlığa sahip olduğunu göstermiştir. AKR1B10 aşırı ifade eden hücrelere kıyasla AKR1B1 aşırı ifade eden hücreler, önemli ölçüde daha yüksek hücresel hareketlilik göstermiş ve bu da önceki verilerimizi doğrulamıştır. RKO hücrelerinde AKR1B1 ve AKR1B10'u aşırı ifade eden hücrelerin RNA sekanslaması, daha önce yüksek AKR1B1 veya AKR1B10 ifade eden tümör numunelerinde (hem epitel hem de stromal bölmelerden ifadelenmeye sahip) oluşturulan gen ontolojisi (GO) terimlerinin RKO hücrelerinde elde edilen GO terimleriyle örtüştüğünü göstermiştir. Buna bağlı olarak, AKR1B1’i aşırı ifade eden hücreler, ROS ile ilgili süreçlerle önemli ölçüde ilişkilendirilirken, AKR1B10’u aşırı ifade eden hücreler, metabolik ve biyosentetik süreçlerin inhibisyonu ile önemli ölçüde ilişkilendirildi.M.S. - Master of Scienc

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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 Under Sail The Imagination of Jack London, 1893-1902

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    In 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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