1,720,953 research outputs found
Development of Abiraterone-based Photoaffinity Probe and Evaluation of their Labeling Efficiency for CYP17A1
No full textAbiraterone 在2012年底經美國食品暨藥物管理局許可，成為治療閹割抗性前列腺癌的二線藥物。其機轉為抑制類固醇生合成路徑中的 CYP17A1 以減少雄性激素的產生。至今大多數的體外實驗或是臨床試驗，為觀測 Abiraterone 影響生合成相關蛋白表現量和上下游產物的分泌量，然而專門探尋未知結合蛋白，所產生的藥物機轉研究卻相對貧乏。在本論文中，我應用 ABPP (Activity-Based Protein Profiling)原理，發展以 Abiraterone 為主體的光親和性探針。此探針是由辨識端Abiraterone、Diazirine光反應性基團和 Biotin為標籤所組成。當辨識端成功與目標蛋白結合時，可藉由 365 nm 波長的光激發使 Diazirine 對目標蛋白產生共價性鍵結，再由 Biotin 標籤做後續的純化或免疫染色。在結構設計上，依據 Docking 實驗結果和已報導的 X-ray 晶體結構，我們選擇 Abiraterone 之 C7a 位置做探針衍生化，以減少與 CYP17A1 結合的干擾。接著我們以單元模組化的合成策略，成功地合成以 Abiraterone 為導引的光親和性探針 Ab-C7a-PB 和 Ab-C7a-P，並以 NMR 技術確認了 C7a 位置的位向。最後進行光親和性探針的功能性鑑定，以 H295 細胞株作為 CYP17A1 來源，in vitro 光標示結果顯示，利用不同的細胞裂解液成分，皆無法萃取出有結合能力的 CYP17A1，故無法成功進行光標示。但以 in vivo 的方式，在維持原始生化功能的細胞組織下，加入 Ab-C7a-PB 進行培養和照光，經後續西方墨漬法分析顯示可成功標示到 CYP17A1。故確認 Ab-C7a-PB 具辨識和光標示的功能性，可用於剖析細胞層級之蛋白質體學研究。Abiraterone, a drug approved by US Food and Drug Administration at the end of 2012 for Castration-Resistant Prostate Cancer, is an inhibitor of CYP17A1, which catalyzes the steroid biosynthesis to produce the androgen in adrenal cortex. Up to date, most in vitro tumor cell lines research or in vivo clinic trials focused on the evaluation of the abiraterone effects on relative protein up/down regulation or the level of specific sterols in the hormonal signal pathways. Research works involving the drug mechanism of action as well as ligand-based protein screening are relatively rare. In this study, I applied the Activity-Based Protein Profiling (ABPP) concept to develop abiraterone-based photoaffinity probes to profile abiraterone’s possible working targets. The probes are composed of abiraterone (ligand) as a recognition unit, daizirine moiety as a photoreactive group and a biotin tag as an output. The working hypothesis is that once the ligand recognized by the target protein, the daizirine could be brought to the vicinity of the target protein and subsequently forms a covalent bond with the target protein upon irradiation at 365 nm. After washing off the nonspecific binding proteins, the covalent-linked proteins can be further purified and characterized either by the tag purification or tag immunohistochemistry via biotin. Based on the molecular docking result and the reported X-ray structure of abiraterone-CYP17A1 ternary complex, abiraterone was derivatized at the C7 position with α configuration to minimize the structural perturbation to bind CYP17A1. The probes, denoted by Ab-C7α-PB and Ab-C7α-P, were successfully synthesized by assembling different functional modules via the designed connectivities. The configuration at C7 was confirmed to be α by several different NMR techniques. To exploit the utility of the probes, H295 cell line was used since it contains abiraterone binding protein-CYP17A1. In vitro photolabeling results showed that Ab-C7α-PB failed to label CYP17A1 by using many kinds of lysis buffers. On the other hand, if Ab-C7α-PB was incubated and photoactivated under native cellular environments in vivo, subsequent Western Blot showed that Ab-C7α-PB could successfully label CYP17A implicating that Ab-C7α-PB could function as an effective photoaffinity probe for labeling CYP17A1 and profiling the abiraterone regulating proteins
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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