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    The Relationship between Intracellular pH and Mechanism of Apoptosis in Rat Cardiomyocytes

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    細胞要維持正常的生理現象,需要仰賴大量的生化反應,而生化反應的進行,細胞內環境的pH值(pHi)扮演很重要的角色。而pHi會受到釵h內在及外在因素的影響,例如細胞本身對氫離子的緩衝能力、細胞外pH值(pHo)和在遭遇一些生理或病理刺激等。近年的研究發現,當細胞發生不可逆的病理過程,例如心肌細胞的缺血傷害後再灌流導致的細胞凋亡時,pHi在此過程扮演著重要的角色:心肌缺血時的酸化現象被認為對於心肌細胞具有保護作用,而此ㄧ保護作用將隨著再灌流細胞pHi回到正常值而失效導致細胞死亡,而其機制尚有爭議;除了上述之病理現象,受到其他藥物刺激所產生的酸化現象卻被認為也能造成細胞的死亡,而非保護細胞。細胞內的鹼化對於細胞的作用同樣尚未有一明確的定論,一般而言鹼化被認為是對細胞體有害的刺激,但是其促使細胞死亡的機制也尚不明朗。在本研究中,我們以較廣泛的角度,觀察初代培養的心肌細胞內的酸化或是鹼化對於細胞產生死亡機制的影響。我們發現若將pHi固定在酸化的狀態pHi=6.5,細胞凋亡(非細胞壞死)現象會有小幅度的提高,但是與pHi固定在鹼化的狀態(pHi=8.0, 8.5)相比,鹼化造成的細胞凋亡的現象則明顯得多。此外,我們也模擬心肌缺血再灌流的酸鹼變化,發現單純的細胞酸化而後回復至正常pHi即會使細胞發生凋亡反應,且引發凋亡的路徑與鈣離子內流無關─此結果也印證了心肌缺血後再灌流造成的細胞凋亡是來自pHi改變的說法。最後,,我們也利用數位式CCD攝影機,來觀察心肌細胞粒線體內pHm(藉由螢光蛋白質mito-EYFP的螢光變化)在上述處理中的變化。我們發現隨著我們調控pHi,pHm也會隨著pHi酸化或鹼化,這意味著pHi改變所引發的凋亡可能有部份是透過影響pHm而達成。Intracellular pH ( pHi ) plays an important role in biochemincal reactions in order to maintain normal cellular functions . Intracellular pH can be varied by many factors, including intracellular buffering power, extracellular pH ( pHo ) and various physiology or pathological stimulation. Recently, it has been proven that pHi is a significant factor during pathogenesis of irreversible cell injury, such as apoptosis induced by reperfusion after ischemic treatment. Acidification during ischemia is thought to have a protective effect and this effect on ischemic cardiomyocytes is eliminated after the restoration of normal pHi by reperfusion. However, intracellular acidification stimulated by some chemicals is thought to be able to induce cell death, not. Similarly, there is no definite conclusion about the effect of cellular alkalinization. It is well known that alkaline conditions are cytotoxic, but the mechanisms leading to alkaline-induced cytotoxicity are still unclear. In the present study, we investigate the effect of acidification and alkalinization on primary culture of rat cardiomyocytes. When we clamped pHi at acidic level, there was a slight increase in ratio of apoptosis ( not necrosis ) . However, clamping pHi at alkaline level ( pHi=8.0, 8.5 ) caused much more severe apoptotic cell death. Furthermore, by simulating the pHi variation during ischemia-reperfusion conditions, we found that pHi recovery from acidification causes apoptosis and is calcium-independent. Our findings supports the hypothesis that apoptosis is induced by pHi recovery during ischemia-reperfusion injury. We also used digital CCD(charge-coupled device)camera imaging techniques to explore the variation of mitochondria matrix pH ( pHm ). We found that pHm varies in parallel to the change of pHi. Therefore, pHm could partly cause the apoptosis induced by pHi variation.圖次 ................................................. Ⅲ 表次 .................................................Ⅴ 中文摘要 .............................................Ⅵ 英文摘要 .............................................Ⅶ 緒論................................................... 1 材料與方法.............................................12 結果...................................................24 討論...................................................33 結論.................................................. 42 圖表................................................. .43 參考文獻...............................................5

    Insecticide Resistance to Pyrethroid in Aedes aegypti

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    高雄市前鎮區、苓雅區(2002)和持續以百滅寧篩選的苓雅篩藥(1990R)品系埃及斑蚊與感性品系的抗性比,成蟲皆大於312.5,於幼蟲則分為20.8、37.5和102.1,故野外品系的蚊蟲抗藥性仍有提升之空間。以WHO的合成除蟲菊酯殺蟲劑藥膜測試2002年台南和高雄埃及斑蚊(Aedes aegypti)成蟲的半數擊昏時間(KT50)和24小時死亡率。高雄巿前鎮區和苓雅區(2002)品系對賽飛寧具抗藥性。高雄巿前鎮區和苓雅區(2002)品系對第滅寧具抗藥性。高雄巿前鎮區、苓雅篩藥(1990R)、苓雅區(2002)和新興區,高雄縣林園鄉和鳳山巿品系對依芬寧具抗藥性。高雄巿前鎮區、苓雅區(2002)、新興區、三民區和左營區,高雄縣林園鄉、岡山鎮和鳳山巿,台南縣歸仁鄉、新巿鄉,和台南巿南區、西區和中區品系對百滅寧產生抗藥性。而高雄巿三民區、左營區和高雄縣岡山鎮品系對賽洛寧具抗藥性。本研究推測埃及斑蚊對百滅寧的抗藥性為2002年南台灣登革熱疫情難以控制的原因之一。2003年高雄市前鎮區、苓雅區和高雄縣鳳山市品系埃及斑蚊對依芬寧和百滅寧仍具抗藥性,但前鎮區和苓雅區對於賽飛寧和第滅寧的抗藥性降低。台南市南區埃及斑蚊對百滅寧和賽洛寧感藥性皆低,為抗藥性較嚴重地區。台南縣歸仁鄉埃及斑蚊對百滅寧和賽洛寧具抗藥性。協力劑測試則顯示埃及斑蚊幼蟲對百滅寧的抗性與氧化The resistance ratios of adult mosquitoes of the Chianjen, Lingya (2002), and Lingya (1900R) strains for permethrin compared to susceptible strains were above 312.5X, while those of the 4th instar larvae were 20.8, 37.5, and 102.1, respectively. We used WHO insecticide-impregnated papers to determine the insecticide susceptibility of adult Aedes aegypti in 2002.. The Chianjen and Lingya (2002) strains showed resistance to cyfluthrin. The Chianjen, Lingya (2002), and Shinshing strains showed resistance to deltamethrin. The Chianjen, Lingya (1990R), Lingya (2002), Shinshing, Linyuan and Fengshan strains showed resistance to etofenprox. The Chianjen, Lingya (2002), Shinshing, Sanmin, Tzuoying, Linyuan, Gangshan, Fengshan, Gueiren, Shinshi, S. District, W. District, and C. District strains showed resistance to permethrin. The Sanmin, Tzuoying, and Gangshan strains showed resistance to lambdacyhalothrin. 2003, the Chianjen, Linya and Fengshan strains of Aedes aegypti were resistant to both etofenprox and permethrin, but the Chianjen and Lingya (2002) reduced resistance to cyfluthrin and deltamethrin. The Tainan South District strain of Aedes aegypti showed the resistant to permethrin and cyhalothrin. The Tainan Gueiren strain of Aedes aegypti showed the resistant to permethrin and cyhalothrin. Results of a synergism study on larvae resistant to permethrin showed correlations to the activities of microsomal monooxygenases and esterases. The highest specific activities of esterase are 0.249目錄.................................. 1 表次.................................. 2 圖次.................................. 3 壹、前言.................................. 5 貳、前人研究.................................. 8 參、材料方法............................. 17 肆、結果............................... 32 伍、討論............................... 43 陸、中文摘要.................................. 54 柒、英文摘要.................................. 57 捌、參考文獻.................................. 59 玖、誌謝.................................. 70 拾、表.................................. 71 拾壹、圖.................................. 8

    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
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