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Investigation of thromboxane A2 synthase knockout mice
No full textThromboxane A2合成酶(TXA2 synthase)所生產的TXA2具有引發血小板凝集、血管收縮及調節腎臟等功能，且在包含心肌梗塞、中風、氣喘及許多的腎臟疾病發生的過程中均扮演重要的角色。除了參與眾所周知的凝血與血栓形成外，TXA2被認為可能參與血小板生成及淋巴球的分化。為了進一步了解其生理功能，本論文以基因轉殖的方式製作TXA2合成酶基因剔除(TXAS-/-)小鼠模式。分析結果發現TXAS-/-小鼠具有正常的骨髓巨核細胞，其胸腺及脾臟的淋巴球數量也正常。但其出血時間異常且以花生四烯酸(arachidonic acid；AA)刺激TXAS-/-小鼠的血小板，血小板無法凝集且無法釋出TXB2，但是prostaglandin-E2 (PGE2)、PGD2及PGF2α的代謝卻增加。以花生四烯酸注入正常的小鼠血管內會造成小鼠血壓急速下降、心跳停止而導致死亡，但TXAS-/-小鼠或是以TP受體拮抗劑(antagonist)處理過的野生型小鼠卻不會休克。進一步實驗發現在花生四烯酸刺激下，當TP受體存在時，TXAS-/-小鼠可維持正常的血壓，但是當TP受體以拮抗劑阻斷時，血壓即下降，此結果顯示受體參與血壓的維持。此外，本論文發現TXAS缺乏會影響花生四烯酸經lipoxygenase路徑中15-HETE及LTB4的生成，顯示TXA2可調節其他發炎介體(inflammatory mediator)的生成。由目前的實驗結果可知，血小板生成及淋巴球的分化不需TXA2合成酶的參與，缺乏TXA2合成酶會有輕微的凝血缺陷，然而對花生四烯酸的刺激較無反應，且不易產生休克及死亡。TXS-/-小鼠模式將是研究與TXA2及花生四烯酸代謝相關病理現象的良好素材。Thromboxane A2 (TXA2) has potent actions on platelet aggregation, vasoconstriction, as well as regulating renal hemodynamics. It plays a role in the pathogenesis of a number of disease states including myocardial infarction, thrombotic stroke, bronchial asthma and a variety of renal diseases. Besides its well-recognized role in hemostasis and thrombosis, thromboxane A2 synthase (TXAS) is proposed to be involved in thrombopoiesis and lymphocyte differentiation. To evaluate its various physiological roles, TXAS-deleted mice was generated by gene targeting. TXAS-/- mice had normal bone marrow megakaryocytes, blood platelet counts, and normal CD4 and CD8 lymphocyte counts in thymus and spleen. Platelets from TXAS-/- mice failed to aggregate or generate thromboxane B2 in response to arachidonic acid (AA) but produced increased PGE2, PGD2 and PGF2α. AA infusion caused a progressive drop of mean arterial pressure (MAP), cardiac arrest and death in WT mice, but did not induce shock in TXAS-/- mice, nor in WT and TXAS-/- mice treated with antagonist to the TP receptor. The TXAS-/- mice were able to maintain normal MAP upon AA insult when TP was present but were unable to do so when TP was blocked by an antagonist, suggesting a role of endoperoxide accumulation in influencing MAP. We also found that TXAS deletion can influence 15-HETE and LTB4 production from lipoxygenase pathway, suggested that TXA2 may regulate inflammatory mediator formation. We conclude that TXAS is not essential for thrombopoiesis and lymphocyte differentiation. Its deficiency causes a mild hemostatic defect and protects mice against arachidonate-induced shock and death. The TXAS-deleted mice will be valuable for investigating the roles of arachidonate metabolic shunt in various pathophysiological processes.摘要 ------------------------------------------------ 1
Abstract ----------------------------------------------- 2
目錄 ----------------------------------------------- 3
圖目錄 ----------------------------------------------- 6
表目錄 ----------------------------------------------- 8
附錄目錄 ---------------------------------------------- 9
縮寫表 ----------------------------------------------- 10
第一章 導論 -------------------------------------- 12
1.1 本章概要 ------------------------------------- 12
1.2 前列腺素的(prostaglandin)早期研究 -------------- 12
1.3 Thromboxane A2 (TXA2)的生成 ------------------- 14
1.4 TXA2的生理功能 ---------------------------- 14
1.5 Thromboxane A2合成酶(TXAS)的分子及生理功能 ------ 15
1.6 TXA2合成酶基因互補DNA的選殖及其重要的氨基酸位置--- 16
1.7 TXA2合成酶的基因結構及多型性對偶基因(allele) ------17
1.8 TXA2合成酶的表現 ---------------------------- 18
1.9 TXA2的受體及基因剔除鼠的相關研究 ---------- 18
1.10 尚待研究的部分及引發本論文的動機 ---------- 19
第二章 TXA2合成酶基因剔除鼠的製造 ------------------- 21
2.1 本章概要 ------------------------------------- 21
2.2 材料與方法 ------------------------------------- 21
2.2.1 小鼠TXA2合成酶genomic DNA基因庫的篩選及基因剔除
載體的構築 ------------------------------------- 21
2.2.2 胚胎幹細胞的培養，轉染及基因剔除胚胎幹細胞的選殖- 22
2.2.3 胚胎幹細胞DNA的製備及南方墨點法 --------- 23
2.2.4 囊胚期細胞注射及嵌合鼠的育種及剔除鼠的基因型鑑定-- 23
2.2.5 反轉錄聚合酶鏈反應(RT-PCR) 及北方墨點法 --------- 24
2.3 結果 ---------------------------------------------- 25
2.3.1 小鼠胚胎幹細胞TXAS基因剔除 ------------------- 25
2.3.2 TXAS-/-小鼠的製造 --- ------------------------ 25
2.4 討論 ---------------------------------------------- 26
2.5 本章結論 ------------------------------------- 27
第三章 TXAS基因剔除鼠的生理及病理分析 ---------- 28
3.1 本章概要 ---------------------------- 28
3.2 材料與方法 ------------------------------------- 28
3.2.1 全血計數，生化分析及病理切片分析 ---------- 28
3.2.2 血小板的電子顯微鏡分析 ------------------- 29
3.2.3 流式細胞儀分析 ---------------------------- 29
3.2.4 出血時間的測量 ---------------------------- 29
3.2.5 血小板凝集及釋放能力分析 ------------------- 30
3.2.6 花生四烯酸(Arachidonic acid)的代謝分析 ---------- 31
3.2.7 小鼠血壓的量測及花生四烯酸引發休克模型 ---------- 31
3.2.8 花生四烯酸代謝產物的測量 -------------------------32
3.2.9 Lipooxygenase代謝路徑相關酵素的RT –PCR分析 ---- 32
3.3結果 ---------------------------------------------- 32
3.3.1 TXAS缺乏不會影響血液中血球組成及血漿中的生化成分-- 32
3.3.2 TXAS缺乏不會影響小鼠主要器官的型態 --------- 33
3.3.3 TXAS缺乏不會影響血小板的生成 ------------------ 33
3.3.4 TXAS缺乏不會影響脾臟及胸腺免疫細胞的組成 ------ 33
3.3.5 TXAS-/-小鼠凝血時間延長且血小板凝集功能異常------ 34
3.3.6 TXAS缺乏的血小板無法代謝AA產生TXA2，且其他產物有
代償性增加的現象 ---------------------------- 35
3.3.7 TXAS缺乏對正常時血壓無影響，但對AA引發的休克反
應具有保護作用 ---------------------------- 35
3.3.8 TXAS缺乏影響AA經lipooxygenase路徑的代謝---------- 36
3.4 討論 ---------------------------------------------- 37
3.5 本章結論 ----------------------------------------- 41
第四章 總結與展望 ----------------------------------- 43
附圖 ---------------------------------------------- 44
附表 ---------------------------------------------- 71
參考文獻 ---------------------------------------------- 77
已發表或投稿之相關論文 ---------------------------- 86
附錄 ------------------------------------------------ 9
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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