1,721,140 research outputs found
Reliability of a MEMS Actuator Improved by Spring Corner Designs and Reshaped Driving Waveforms
No full textAn electro-magnetic micromachined actuator monolithically integrated with a vertical shutter for variable optical attenuation
No full text
Thornton Wilder’s Ordinary Town: An Adaptation Case Study
No full text桑頓懷爾德（1897-1975）是跨了兩個文類的普立茲獎得主，分別是小說類1927年的《聖路易里之橋》——義大利教士在秘魯的故事，以及劇本1938年的《小鎮》——背景在新英格蘭，以及1942年的《九死一生》——背景是在冰河時期的紐澤西，這樣弔詭的組合。學者們認為懷爾德的作品中充滿人文主義元素，在戰爭時期肯定著某些價值。他的《小鎮》被認為是以平凡生活中的普世價值與世界連接。本論文不傾向連結感的解讀，而是透過後人類、疏離現象來詮釋懷爾德，進而理解他所謂的『平凡』。 第一章透過懷爾德的書信探討他人生中的連結與疏離關係。懷爾德是他的時代中優秀作家之一，其中包括了小說家恩尼斯特海明威以及史考特費滋傑羅。學者認為身為人文主義者的懷爾德跟悲觀地面對世界大戰的失落一代作家不同。但，透過書信的檢視發現，懷爾德雖然不失落，但是是疏離的。這樣的定位讓他能夠透過疏離的角度探討人生的意義。 第二章以懷爾德的改編作家身份出發。遠離美國的懷爾德從古代文明中尋找改編元素。他對神話特別有興趣。他認為，神話是一種能夠一直被說下去的文體。但，不像一般傳統神話以英雄或重要的人物為題，懷爾德的神話則是為了那些在歷史的流動中被疏離的『不重要』的人物而寫的。為了他的凡夫俗子人物，懷爾德需要一個不受時間束縛的舞台，一個極簡主義的舞台，讓這些被困在寫實舞台中特定時間點的人物重獲自由。 第三章檢視《小鎮》中的疏離效應。這部劇本是人生階段的縮影。第一幕一開始是小鎮平凡的一天。艾蜜莉與喬治在第二幕結為連理。最後一幕，艾蜜莉死於難產。這部劇是由『舞台監督』這個角色當旁白。學者認為舞台監督這個角色打破了第四牆並與觀眾連結。但，他並不是真的跟觀眾互動，而是表演著連結的假象。這樣連結的假象也出現在小鎮人民的關係裡。小鎮人民按照著社會期望在過日子。舞台監督則是引導著他們表演『平凡的行為』，但，一旦鎮民的台詞偏離了期待的平凡，舞台監督會打斷他們的對白。在這樣極簡主義的舞台中，鎮民能夠清楚地看到對方，但依然被隱形的平凡疏離了。 第四章分析《小鎮》的改編電影劇本。1939年，懷爾德接受了製片索雷瑟的請求，並答應當《小鎮》劇本改編的顧問。極簡主義的舞台是原作中重要的元素，但電影劇本卻是視覺化的語言，必須要有精確的背景設定。這樣的根本性媒體差異卻更能讓觀眾了解懷爾德所謂的平凡小鎮。在改編的過程中，懷爾德認為雷瑟改變的一些場景無法重現他原作的想法。兩人的爭論結果顯示出懷爾德的平凡代表著被社會的期望所疏離的每個人。 第五章討論的是在1940年上映的《小鎮》電影作品。視覺的電影語言改變了原著的意義。鏡頭變成了電影的旁白。電影中，窗戶與框架比喻著禁錮人民的社會期待。儘管視覺化無法完全呈現原著中隱形的壓迫感，視覺的比喻卻也解釋了原著中難以呈現的平凡感。 結論：懷爾德是在美國文學中被疏離的作家。這樣的狀態讓他能夠去發現並改編外國的元素。與他同世代的作家相比，懷爾德並沒有對人性失去信心，而是去質問這無形的敵人——狡猾的平凡。Thornton Wilder (1897-1975) was a Pulitzer Prize winner in two genres for the novel The Bridge of San Luis Rey (1927), a story about an Italian priest in Peru, and for the play Our Town (1938), which he set in New England, and The Skin of Our Teeth (1942), which was bizarrely set in Ice Age New Jersey. Scholars recognize the Humanistic elements in Wilder’s works, which affirm certain values during the wartime. His stage play Our Town, is considered as a work that connects the world with a universal value of ordinary lives. Instead of praising the connectedness, this dissertation aims to offer a Post-Humanistic, alienation reading of Wilder to find out his sense of the “ordinary.” Chapter One investigates Wilder’s letters to find out his connectedness and alienation in his life. Wilder was one of the best writers of his generation, which included the novelist Ernest Hemingway and Scott Fitzgerald. Scholars read Wilder as a Humanist and considered that Wilder was distinguished from the Lost Generation writers, who pessimistically responded to the world war. Yet, through the investigation of their letters, Wilder was not lost but alienated, which enabled him to pursue the meditation on life from the perspective of alienation. Chapter Two reads Wilder as an adaptor. Being alienated from his America, Wilder adapts from ancient civilization for his works. He was interested in myth, which he considered to be a form that is continuously told. Yet, unlike traditional myths, which are about heroes or significant people, Wilder’s myths are written for the insignificant ordinaries that are alienated in the flow of history. In order to create a timeless stage for the stories of his insignificant characters to be told, he creates a minimalistic staging, which frees the characters from the realistic, confined moment. Chapter Three examines the alienation effect in Our Town. The play is a miniature of the course of life. It begins with an ordinary day in the town in the first act. Emily and George get married in the second act. Emily dies during childbirth in the last act. The Stage Manager, a character, narrates the play. Scholars understand the Stage Manager breaking the fourth wall and connecting to the audience. However, he does not really interact with the audience, but performs artificial connection. This artificial connection prevails in the relationship of the townspeople as well. The townspeople follow the expectation set by the society. The Stage Manager directs the scenes of these “ordinary behaviors,” but when the townspeople’s dialogues stray from expectation, the Stage Manager interrupts them. On a minimalistic stage, the townspeople are allowed to see each other, but they are alienated from each other by the invisible ordinariness. Chapter Four analyzes the screenplay adaptation of Our Town. In 1939, Wilder accepted the request from a film producer Sol Lesser, who asked for consultation for adapting Our Town into a screenplay. Minimalism is essential for the original stage play, but the screenplay is visualized language, with specific scenery. These fundamental media differences provide insights for a better understanding of Wilder’s ordinary town. In the process of adaptation, Wilder argued with Lesser for the scenes that could not represent his idea. Based on their arguments, this chapter concludes that Wilder’s ordinary is the social expectation that alienates the individuals. Chapter Five discusses the film production of Our Town, which was premiered in 1940. The visualized film language changes the message of the play. The camera narrates the film. The windows and frames become the metaphor for the social expectations that confines people. Although the visualization could not fully represent the literal invisibility of the oppression, the visible metaphor actually helps to understand the inaccessible ordinariness in the original play. In conclusion: Thornton Wilder is an alienated writer in American literature. This condition allows him to discover and adapts the foreign sources. In comparison with his contemporary writers, instead of losing faith in humanity, Wilder poses questions against the invisible enemy – the insidious ordinariness
論行政法人的建制-以民主正當性理論與責任政治原則為中心
No full text以效能、彈性、專業與去政治化為建制理念的行政法人制度，在我國乃是一項全新的制度。雖然，行政法人建制的背景符合我國的需求，特別是為了因應全球化的競爭壓力，期以公私混合的彈性組織，結合民間力量、發揮效率，並且迅速回應國際競爭壓力。但是，行政法人建制卻引起各界諸多質疑。同時，此等質疑的焦點乃是集中在對於行政法人的民主正當性與責任監督不足之關切。從而，在經過進一步探討這些質疑背後原由，本文歸納出這些質疑往往陷入傳統憲政主義的窠臼。亦即，狹隘地以代議民主為中心的傳統民主原則，以及以國會監督為本位的責任政治原則來檢視行政法人建制。
然而，本文發現，傳統的代議民主與責任政治原則已經逐漸地產生變動。首先，民主正當性理論的變遷乃是從獨尊國會民主正當性的傳送帶理論，到主張行政權自有正當性而毋庸依賴國會傳送的專業理論、參與理論、尊嚴理論、新民主理念、憲政民主正當性理論，以及全球化觀點的民主正當性理論。其次，以國會監督本位的責任政治原則，其內涵亦逐漸發生變遷。亦即，從傳統偏向紅燈理論、權力限制論、層級節制與責任監督等對於行政權採取限制權力的面向，逐漸轉向綠燈理論、議題整合論、績效課責、管理效率等強調提升行政權的效率與效能，甚至，責任政治原則與新民主原則結合。亦即，主張決策過程應更為透明公開、有更多參與暨論辯。因此，要求行政法人必須有國會立法傳送民主正當性，以及須由國會直接監督行政法人已非必然。
所以，在新的民主與責任理論的基礎上。本文希望透過行政法人建制的再形塑，其包括藉由行政法人的透明公開制度、行政法人的參與制度、行政法人的論辯制度、國會仍維持一定的直接與間接監督機制來監督行政法人，以及事後的績效課責的制度與救濟機制。一方面，化解對於行政法人之民主正當性疑義與責任監督不足的質疑，另一方面，能夠提升行政法人的效率和效能。
再者，在本文所論述的新理論與新制度的基礎上，本文乃分別自行政法人的設立規定、行政法人的人事任命制度、行政法人的決策程序、行政法人監督制度等四個面向，檢討目前我國行政法人法草案的制度設計，並且提出應進一步補強與再形塑我國行政法人建制的制度設計，以作為未來的立法建議。最後，本文認為這些制度設計，應該有積極的機關內部文化和主動積極的公民意識作為制度配套，以使行政法人建制運作良善。With the goal of effect, flexibility, profession and depoliticization, administrative corporation is established as an all-new system in our country. Although, the administrative corporation is set up to meet the need of Taiwan's governmental reform, especially for responding the competition pressure of the globalization, which is expected to combine with the civil power, to promote efficiency, and to respond to the international competition pressure quickly through the flexible public and private hybrid organization. However, the administrative corporation has caused the public many queries. Meanwhile, these queries focus on concerns about the democratic legitimacy and accountabilities of the administrative corporation. Thus, through a further study for the reasons of these queries, this text induces that the key reasoning of these concerns is usually to get bogged down in the traditional constitutional government doctrines. That is, narrowly by representative democracy-centered traditional democracy principle, and by the principle of political accountability based on the legislature-supervised to examine the system of administrative corporation.
However, this text detect that, the principle of traditional representative democracy and the principle of political accountability have already produced the fluctuation gradually. Firstly, the theory of democratic legitimacy has changed, which is from focused on the legislature transmits legitimacy to the executive (i.e. transmission belt theory) to focused on claiming that the executive is able to be legitimized from profession, participation, dignitary procedure, new democratic participation, dualist democracy, and the global perspective democratic legitimacy. Secondly, the content of the political accountability principle based on the legislature-supervised also changes gradually. That is, from the dimension that inclines towards restriction on the administrative power to the dimension that inclines towards emphasis on promoting the efficiency and the effect of the administrative power. Even, the political accountability principle combines with the new democracy principle. That is, assert to make the process of policy much more transparent and open, and make much more participation and deliberation in the procedure of policy-making. Therefore, it is unnecessary to insist that by簡 目
1.緒論 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ １
1.1.研究目的與範圍 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ １
1.2.研究限制‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥３
1.3.論文架構與本文論點 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ ３
2.行政法人建制的形塑 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ ９
2.1.行政法人建制的背景 ‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ ９
2.2.我國行政法人建制的背景‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１５
2.3.行政法人化政策之提出‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１７
2.4.行政法人的定義與建制理念‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥２２
2.5.行政法人的法源依據與個案推動現況‥‥‥‥‥‥‥‥‥‥‥‥‥２６
2.6.行政法人的制度設計‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥２８
2.7.小結‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥３３
3.行政法人建制的質疑‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥３５
3.1.設立行政法人的民主正當性‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥３６
3.2.行政法人行使公權力的民主正當性‥‥‥‥‥‥‥‥‥‥‥‥‥‥４０
3.3.行政法人制定規章的民主正當性‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥４１
3.4.行政法人國會監督不足的質疑‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥４４
3.5.質疑歸結：陷入傳統憲政主義的窠臼‥‥‥‥‥‥‥‥‥‥‥‥‥４６
4.變遷中的民主正當性理論與責任政治原則 ‥‥‥‥‥‥‥‥‥‥‥‥‥４８
4.1.變遷中的民主正當性理論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥４８
4.2.變遷中的責任政治原則‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥５６
4.3.小結‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥６１
5.行政法人建制的再形塑‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥６４
5.1.行政法人的透明公開‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥６４
5.2.行政法人的參與‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥７１
5.3.行政法人的論辯‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥７５
5.4.行政法人向國會負責之機制‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥７６
5.5.替代國會監督的制度‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥７８
5.6.小結‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥８２
6.行政法人法草案的檢討與補強‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥８４
6.1.行政法人設立規定之檢討‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥８４
6.2.行政法人的人事任命制度之檢討‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥８７
6.3.行政法人的決策程序檢討‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥９２
6.4.行政法人監督制度檢討‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥９７
6.5.小結‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１０４
6.6.制度配套‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１０５
7.結論與立法建議‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１０８
7.1.結論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１０８
7.2.行政法人法草案的立法建議‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１０９
參考文獻‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１１５
附錄‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥１２
Oral Bioavailability of Sesamol in Rats
No full text芝麻酚 (sesamol) 為芝麻油中一種抗氧化物質，其主要是在芝麻油脫色的步驟或芝麻種子炒焙的過程中，由 sesamolin 所產生。本實驗之目的為利用微透析技術採樣及傳統之全血採樣方法，探討芝麻酚在大白鼠之藥物動力學及口服生物可利用率。
本實驗中，利用微透析技術採樣，並建立一快速而檢測靈敏度高之高效液相層析分析方法，測定透析液中芝麻酚含量，以探討非結合態芝麻酚於大白鼠體內之藥物動力學。微透析技術是大白鼠於麻醉狀態下將微透析探針同時置入其頸靜脈、膽管、腦部之紋狀體及肝臟中葉，以進行採樣，另由股靜脈注射給藥。高效液相層析之分離管柱是採用逆向碳 18 管柱 (4.6 mm i.d. × 250 mm, 4 μm particle size)，移動相是由 acetonitrile 及 10 mM 磷酸二氫鈉水溶液以體積比 35:65 所組成，再以磷酸調整 pH 值至 4.0，流速為 1 ml/min，紫外光偵測波長設定在 294 nm。結果顯示，由股靜脈注射給予 30 mg/kg 之芝麻酚後，芝麻酚在血液、膽汁、腦部及肝臟之最高濃度 (Cmax) 分別為 8.36 ± 1.47、2.65 ± 0.63、3.33 ± 0.55 及 1.17 ± 0.14 μg/ml；藥物半衰期 (t1/2) 分別為 7.51 ± 1.01、10.3 ± 4.0、6.49 ± 2.18 及 6.49 ± 1.14 min；藥物濃度對時間曲線下面積 (AUC) 分別為 75.3 ± 18.2、44.1 ± 8.3、44.0 ± 7.0 及 11.4 ± 7.6 min μg/ml。分布係數可由組織所測得之 AUC 與血液之 AUC 之比值計算而得，芝麻酚之膽血分布係數 (AUCbile/AUCblood) 為 0.602 ± 0.126，腦血分布係數 (AUCbrain/AUCblood) 為 0.603 ± 0.120，而肝血分布係數 (AUCliver/AUCblood) 為 0.140 ± 0.074。此結果亦指出芝麻酚可通過血腦障壁 (BBB)，並且會由膽汁排泄。口服生物可利用率為藥物給予後，到達體循環之原型藥與給藥劑量之比例。芝麻酚分別以胃管強迫餵食及靜脈注射給予後，於特定之時間點進行採血，再利用高效液相層析分析方法，測定血漿中總芝麻酚濃度。高效液相層析之條件與為透析採樣時相同，但移動相之 pH 值修改為 4.15。在以胃管強迫餵食 30、100 和 300 mg/kg 以及由靜脈注射給予 30 mg/kg 之劑量後，芝麻酚在血漿中最高濃度 (Cmax) 分別為 11.2 ± 6.2、22.2 ± 7.3、60.5 ± 14.0 及 38.8 ± 16.8 μg/ml；藥物半衰期 (t1/2) 分別為 9.43 ± 4.33、13.2 ± 4.9、11.1 ± 2.4 及 15.3 ± 5.8 min；血漿濃度對時間曲線下面積 (AUC) 分別為 110 ± 70、443 ± 150、1140 ± 360 及 343 ± 96 min μg/ml。此結果顯示，芝麻酚於血漿中之濃度下降迅速；在 30 – 300 mg/kg 之劑量範圍內，芝麻酚之藥物半衰期與劑量無關，而 AUC 則隨劑量增加成比例增加，推測在此劑量範圍內芝麻酚呈線性藥物動力學。芝麻酚在大鼠之口服生物可利用率為 34.8%；另外，芝麻酚在血漿中之蛋白質結合率為 82.8%。Sesamol (benzo[1,3]dioxol-5-ol) has been generally regarded as the main antioxidative component in sesame oil. It was produced from sesamolin during the bleaching process of sesame oil with acid clay or upon roasting of sesame seed. The purpose of this study was to investigate the oral bioavailability and pharmacokinetic characteristics of sesamol in rats, both microdialysis and traditional blood sampling methods were employed. We developed a rapid and sensitive high performance liquid chromatographic method coupled with microdialysis system to measure the unbound sesamol from various biological fluids. Multiple microdialysis probes were concurrently inserted into the jugular vein, bile duct, brain striatum and the median lobe of liver of each anesthetized rat for sampling after sesamol administration (30 mg/kg) through the femoral vein. Separation of the unbound sesamol from various biological fluids was performed by a reversed phase C18 column (4.6 mm i.d. × 250 mm, 4 μm particle size). The mobile phase consisted of acetonitrile-10 mM sodium dihydrogen phosphate buffer (35:65, v/v) (adjusted to pH 4.0 with phosphoric acid) at a flow rate of 1 ml/min. The UV detector wavelength was set at 294 nm. The results showed that the maximum concentration of sesamol in blood, bile, brain and liver were 8.36 ± 1.47, 2.65 ± 0.63, 3.33 ± 0.55 and 1.17 ± 0.14 μg/ml; the half-lives were 7.51 ± 1.01, 10.3 ± 4.0, 6.49 ± 2.18 and 6.49 ± 1.14 min; the area under the concentration versus time curves (AUCs) were 75.3 ± 18.2, 44.1 ± 8.3, 44.0 ± 7.0 and 11.4 ± 7.6 min μg/ml, respectively. The extent of systemic unbound sesamol distributed to bile, brain and liver, calculated as AUCbile/AUCblood, AUCbrain/AUCblood and AUCliver/AUCblood were 0.602 ± 0.126, 0.603 ± 0.120 and 0.140 ± 0.074. In addition, the results indicated that sesamol penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion. The oral bioavailability is defined as the fraction of the dose which reaches the systemic circulation as intact drug. Blood samples were collected at various time intervals after sesamol administration and then assayed by a validated HPLC system. The separation of sesamol in rat plasma was performed under the similar HPLC condition as in the microdialysis samples except the mobile phase was adjusted to pH 4.15. After sesamol administration (30, 100 and 300 mg/kg, p.o. and 30 mg/kg, i.v.), the maximum concentration of sesamol were 11.2 ± 6.2, 22.2 ± 7.3, 60.5 ± 14.0 and 38.8 ± 16.8 μg/ml; the half-lives were 9.43 ± 4.33, 13.2 ± 4.9, 11.1 ± 2.4 and 15.3 ± 5.8 min; AUCs were 110 ± 70, 443 ± 150, 1140 ± 360 and 343 ± 96 min μg/ml, respectively. The results showed that the concentrations of sesamol declined rapidly and the elimination half-lives did not relate to the dosage ranges. AUCs presented dose dependent manner. These results suggested that sesamol appears a linear pharmacokinetic phenomenon. The oral bioavailability of sesamol was 34.8% in rats. The protein binding ratio of sesamol was 82.8% in rat plasma.中文摘要 I
英文摘要 III
目錄 V
圖目錄 IX
表目錄 XI
壹、文獻整理
一、芝麻之 lignan 化合物
1. 芝麻簡介 1
2. 芝麻中 lignan 化合物簡介 2
3. 芝麻 lignan 化合物之化學變化 3
4. 芝麻之生理機能 5
5. 芝麻 lignan 化合物之生物可利用率 10
6. 其他天然化合物之生物可利用率 12
二、藥物動力學 (Pharmacokinetics)
1. 藥物動力學簡介 17
2. 藥物動力學參數 17
3. 藥物動力學模式 18
4. 線性及非線性藥物動力學 20
5. 生物可利用率 21
三、微透析 (Microdialysis)
1. 微透析簡介 22
2. 微透析在活體內之應用 24
貳、研究動機與實驗架構
一 、研究動機 25
二、實驗架構 26
參、材料與方法
一、實驗材料
1. 試藥與試劑 27
2. 高效液相層析系統 28
3. 微透析裝置 28
4. 其他儀器設備 29
5. 實驗動物 31
6. 藥物動力學計算軟體 31
二、實驗方法
1. 利用微透析技術探討大白鼠體內未結合態芝麻酚之藥物動力學
(1) 溶液之配製 32
(2) 高效液相層析分析條件 33
(3) 檢量線之製作及分析方法之確效 33
(4) 微透析技術採樣 34
(5) 微透析之體內回收率測定 35
(6) 藥物動力學參數之計算 35
(7) 統計分析 36
2. 利用傳統採樣方法探討大白鼠血漿中總芝麻酚之藥物動力學
(1) 溶液之配製 36
(2) 高效液相層析分析條件 37
(3) 檢量線之製作及分析方法之確效 37
(4) 傳統採血法採樣 38
(5) 傳統採血法之回收率測定 39
(6) 藥物動力學參數之計算 39
(7) 統計分析 39
3. 芝麻酚在血漿中之蛋白質結合率
(1) 血漿中蛋白質結合率之測定 40
(2) 統計分析 40
肆、結果
一、利用微透析技術探討大白鼠體內未結合態芝麻酚之分析結果
1. 血液、膽汁、腦部及肝臟透析液中芝麻酚之高效液相層析分析 42
2. 芝麻酚分析方法之確效 42
3. 血液、膽汁、腦部及肝臟微透析探針之體內回收率 43
4. 芝麻酚在血液、膽汁、腦部及肝臟透析液中濃度之經時變化 43
5. 利用微透析技術探討未結合態芝麻酚之藥物動力學 44
二、大白鼠血漿中總芝麻酚之分析結果
1. 血漿中總芝麻酚之高效液相層析分析 45
2. 血漿中總芝麻酚分析方法之確認 45
3. 血漿中總芝麻酚之回收率 45
4. 血漿中總芝麻酚濃度之經時變化 46
5. 血漿中總芝麻酚之藥物動力學及其口服生物可利用率 46
三、芝麻酚在血漿中之蛋白結合率 48
伍、討論
一、芝麻酚之高效液相層析分析 49
二、芝麻酚之藥物動力學
1. 利用微透析技術探討未結合態芝麻酚之藥物動力學 50
2. 利用傳統採樣方法探討總芝麻酚之藥物動力學及其口服生物可利用率 51
三、芝麻酚在血漿中之蛋白結合率 53
陸、結論 56
參考文獻 5
Generalized Inferences on Problems in Biostatistics
No full text本研究主要探討廣義推論(generalized inference)在生物統計之應用。研究主要分成三個部份。體外溶離率試驗已被建議用來替代藥物生體相等性試驗來進行變化前後藥品的相似性之評估。研究的第一部份主要是利用廣義p值(generalized p-value)的概念，在體外溶離率試驗下進行變化前後藥品的相似性之評估。美國食品藥物管理局(FDA)已公告數個有關核准後藥品變化評估的準則。這些公告中所提出評估溶離率剖析曲線(dissolution profile)相似性的標準為根據溶解度平均差均方如相似因子f2，或溶解度平均差絕對值的平均如相似因子g1而訂定。由於相似因子f2與g1的分配複雜不易推導求得，故進行溶離率剖析曲線相似性的檢定就相對困難。因此我們嘗試透過廣義p值(generalized p-value)的概念來進行溶離率剖析曲線的相似性之評估，透過大型的模擬試驗在不同溶解度平均數差、變異數及藥品樣本數下，探討該統計方法之偏差、型I誤差與檢定力並與拔靴法(bootstrap method)的結果做比較。模擬結果發現，以相似因子f2與g1作為評估溶離率剖析曲線相似性的準則時，隨著藥品樣本數愈大，廣義p值與拔靴法的評估表現一樣好。最後透過一個實例以相似因子f2與g1作為評估溶離率剖析曲線相似性的準則時，針對廣義p值法與拔靴法作比較。受者操作特徵曲線(receiver operating characteristic curve)簡稱ROC曲線，是常用來評估診斷工具準確性的統計方法。在診斷試驗中，比較新診斷工具與現行標準診斷工具的準確性是一項重要的課題。當黃金標準試驗(gold standard test)存在時，一般常以ROC曲線下面積作為評估診斷工具準確性的指標。然而有些情形下，黃金標準試驗執行費用太昂貴或是黃金標準試驗無法取得。故研究的第二部份主要是討論在常態性假設下，當黃金標準試驗不存在時，利用EM演算法及拔靴法，提出以最大概似法(maximum likelihood method)為基礎的統計程序，針對成對(paired)ROC曲線下面積建立其信賴區間之研究。透過大規模的統計模擬研究可驗證，當黃金標準試驗不存在時，我們提出的區間估計能提供足夠的覆蓋機率(coverage probability)。此外我們亦利用廣義樞紐量(generalized pivotal quantity)來建立當黃金標準試驗不存在時成對ROC曲線下面積的廣義信賴區間(generalized confidence interval)。由統計模擬研究可驗證，當黃金標準試驗不存在時，成對ROC曲線下面積的廣義信賴區間亦能提供足夠的覆蓋機率。最後，利用提出之方法針對胰臟癌(pancreatic cancer)、動脈硬化症(atherosclerosis)等實際診斷資料進行分析。三部份利用廣義p值的概念，當變異數異質(heteroscedasticity)時，評估新處理(new treatment)在three-arm試驗中，的非劣性(non-inferiority)。透過模擬試驗，在不同變異數及樣本數組合下，探討提出統計方法之型I誤差與檢定力。一般而論，我們提出的方法之型I誤差均能接近宣稱的水準(nominal level)，其檢定力優於Fieller''s法與拔靴法。最後，利用提出之統計方法針對兩個實例進行資料分析。The main objective of this dissertation is to use generalized inference on biostatistics. There are three parts in this dissertation. In vitro dissolution testing has been suggested as a surrogate for assessment of bioequivalence between the test and reference formulations for postapproval changes. First is that we use the concept of generalized p-values (GPVs) to assessment of similarity between dissolution profiles. The often used criteria for assessment of dissolution similarity between general profiles are functions of average squared mean differences and absolute mean difference. Because of the complexity of the distributions of estimators of two functions, it is difficult to obtain a test to test the hypothesis of dissolution similarity. Therefore, in first study, the GPVs is applied to construct a test procedure to assess the similarity of dissolution profiles. Simulation results show that when the numbers of dosage units are large, the GPVs testing procedure yields satisfactory results for size and power with f2 and g1 criteria recommended by the U.S. Food and Drug Administration (FDA). Through this simulation study, with the same f2 and g1 criteria, the performance of empirical sizes and empirical power by using GPVs are as good as by using bootstrap method. The proposed method is illustrated with a real example.he receiver operating characteristic (ROC) curve is a popular statistical tool for the accuracy of diagnostic device. One of primary objectives in a diagnostic test evaluation study is to compare the diagnostic accuracy of the new diagnostic procedure with that of current standard procedure. The second part is that we construct confidence intervals for the difference in paired areas under ROC curves in the absence of a gold standard test. The ROC curves can be used to assess the accuracy of tests measured on ordinal or continuous scales. The most commonly used measure for the overall diagnostic accuracy of continuously valued diagnostic tests is the area under the ROC curve. To estimate such a measure, we require the existence of a gold standard test on the presence of disease status. However a gold standard test may sometimes be too expensive or infeasible to obtain. Therefore, in many medical research studies, the true disease status of the subjects may not be known or available. Under the normality assumption on the diagnostic test results from each group of subjects, based on the expectation-maximization (EM) algorithm in conjunction with a bootstrap method, we propose a maximum likelihood based procedure for construction of confidence intervals for the difference in paired areas under ROC curves in the absence of a gold standard test. In addition, we also propose to use the concept of generalized pivotal quantities (GPQs) to construct generalized confidence intervals (GCIs) for the difference in paired areas under ROC curves in the absence of a gold standard test. Simulation results show that the proposed interval estimation procedures yield satisfactory coverage probabilities and expected lengths. The proposed methods are illustrated with two data examples.he last part is that we propose a generalized inference on assessment non-inferiority of a new treatment in a three-arm trial in the presence of heteroscedasticity. In non-inferiority trials, the goal is to show how an experimental treatment is statistically and clinically not inferior to the active control. The three-arm clinical trial usually recommended for non-inferiority trials by the FDA. The three-arm trial consists of a placebo, reference, and an experimental treatment. In this study, under the normality assumption on the placebo, reference, and an experimental treatment, the GPVs is applied to facilitate non-inferiority tests in a three-arm design. In the situation of heterogeneous group variances, through a simulation study, the GPVs will adequately maintain the alpha level than Fieller''s method and bootstrap method. Simulation results also show that the performance of empirical power of GPVs method is as good as that of the Fieller''s method and the bootstrap method. Finally, the proposed method is illustrated with two data examples.Contents Introduction 1.1 Assessment of similarity between dissolution profiles 2.2 The paired areas under the ROC curves in the absence of a gold standard . 4.3 Assessment non-inferiority of a new treatment in a three-arm trial in theresence of heteroscedasticity . 6.4 Organization of the dissertation . 7 Preliminaries of Generalized Statistical Inference 8.1 Generalized p-values. 8.2 Generalized confidence intervals . 9 A Generalized Inference on Assessment of Similarity between Dissolutionrofiles 11.1 Criteria and Formulation of Hypothesis for Dissolution Profile Similarity . 12.1.1 Similarity criterion based on squared mean difference . 12.1.2 Similarity criterion based on absolute mean difference. 13.2 Generalized inference on similarity factor f2 and g1 14.3 Simulation Study and Results 18.3.1 Simulation study on empirical bias. 18.3.2 Simulation study on type I error rate 19.3.3 Simulation study on power . 23.4 Numerical Examples. 26.5 Conclusion and Final Remarks. 28 Interval Estimation by Using ML-Based Method for the Difference inaired Areas under the ROC Curves in the Absence of a Gold Standard 32.1 The Proposed ML-BasedMethod 33.1.1 EM algorithm . 34.1.2 Bootstrap method 36.2 Simulation Studies 37.2.1 Simulation study I 37.2.2 Simulation study II42.2.3 Simulation study III 42.3 Numerical Examples 45.3.1 The study of pancreatic cancer serum biomarkers 45.3.2 The study of accuracy of magnetic resonance angiography (MRA)eadings by two readers 46.4 Discussion and Final Remarks 47 Generalized Confidence Interval Estimation for the Difference in Pairedreas under the ROC Curves in the Absence of a Gold Standard 50.1 Generalized Confidence Interval Estimation 51.2 Simulation Studies 55.3 Numerical Examples 60.3.1 The study of pancreatic cancer serum biomarkers 60.3.2 The study of accuracy of magnetic resonance angiography (MRA)eadings by two readers61.4 Discussion and Final Remarks 62 A generalized inference on assessment non-inferiority of a new treatmentn a three-arm trial in the presence of heteroscedasticity 63.1 Introduction 63.2 Statistical Background and Non-inferiority Hypothesis 64.3 Generalized inference on the ratio of the differences inmeans 67.4 Simulation Study 70.4.1 Simulation study on type I error rate 71.4.2 Simulation study on power 84.5 Numerical Examples 88.5.1 A comparative study inmildly asthmatic patients88.5.2 Evaluation of themutagenicity example 89.6 Conclusion and Final Remarks 91 Future Research 92ibliography 95 Appendix A 102 Appendix B: The estimators in M-step 10
Vibration Attenuation of Vehicle Exhaust Structures
No full text排氣系統為附掛在車輛底盤上的次結構，很容易被簡化處理，若處理不慎可能引起共振或振動能量集中於局部而導致結構噪音或掛架斷裂，甚至有局部拍擊的現象，降低行車品質。本文提出一套車輛排氣結構系統的動態特性分析與設計參數調整自動化的「結構動態分析為基礎的設計最佳化」運算程序。
首先建立排氣管有限元素分析模型，接著以敲擊試驗，運用系統識別確定排氣管結構的模態參數，以此為依據修正有限元素模型的未確定參數。
其次將實車量測到的主機排氣口段加速度資料，換算成位移頻譜作為主機排氣口的外力頻譜，利用ANSYS諧和分析算出頻率反應函數，兩者結合計算排氣結構系統動態反應頻譜。
最後應用最佳化方法，以尋找排氣系統的吊掛結構材料參數與掛吊位置的變更方式，以降低排氣管吊點反力頻譜峰值，達到最低振動量的目標，排除排氣系統振動傳遞到車體的結構噪音問題。The exhaust structure system is the sub-system hung under the vehicle chassis. This sub-system may be considered rashly as a simple structure. If the structure system is arrayed unreasonably, the structure resonance or the concentration of vibration energy on local area will accrue, which will induce structure noise or damage of mountings components. Farther more the structure components may pound together and the ridding quality will be reduced. This paper proposed a dynamic analysis based optimization procedure to reduce the vibration level of the vehicle exhaust structure system.
At first, the FEM model with initial parameters is established, and then this parameter will be modified in accordance with the modal parameters which are identified form vibration test.
Secondly, the acceleration of the exhaust pipe on air vent section will be measured in car running test, and then converted into displacement spectrum used as input exciting spectrum. The frequency response functions of exhaust structure are determined by harmonic analysis using ANSYS. And then the dynamic response spectrum can be calculated.
Finally, the equivalent elastic modulus and the location of the suspension rubber can be optimized to achieve the minimum reaction forces of suspension rubber. So that the noise and vibration in the body transmitted from the exhaust system should be reduced to a minimum level.中文摘要 i
英文摘要（Abstract） ii
目錄 iii
表目錄 v
圖目錄 vi
第一章：導論 1
1.1研究動機與目的……………………………………… 1
1.2文獻回顧……………………………………………… 3
1.3本文架構……………………………………………… 4
第二章：結構動態特性分析基本理論 6
2.1結構動態特性理論……..…………………………… 6
2.2振動量表示法………………………………………… 10
2.2.1傅利葉轉換…………………………………… 10
2.2.2功率頻譜密度………………………………… 12
第三章：排氣系統的有限元素分析模型及模型修正 14
3.1有限元素分析模型…………………………………… 14
3.2 利用敲擊試驗修正有限元素模型參數…………… 19
3.2.1 主機出氣段之軟管等效彈性模數之修正…… 20
3.2.2 懸吊彈性橡膠吊環之等效彈性模數的修正… 25
3.3 排氣管四段結構分段敲擊試驗與參數修正……… 33
3.3.1 主機出氣口段硬管等效彈性模數E1之修正… 33
3.3.2 觸媒轉換器段等效彈性模數E2之修正……… 34
3.3.3 排氣管中段管壁等效彈性模數E3之修正…… 36
3.3.4 消音器段外殼等效彈性模數E41之修正…… 38
3.4 實車全段排氣管敲擊試驗與模態量測識別……… 39
第四章：ARTC實車振動與噪音量測 43
4.1 實驗規劃…………………………………………… 43
4.2實驗分析結果與討論………………………………… 46
4.2.1 實驗分析結果………………………………… 46
4.2.2 實驗結果討論………………………………… 60
第五章：排氣管最佳減振探討 63
5.1排氣管系統頻率反應分析…………………………… 63
5.1.1 諧和反應分析………………………………… 64
5.1.2 結構動態反應頻譜…………………………… 65
5.2 排氣系統吊點選擇結構模態節點之探討…………… 65
5.3 以諧和反應分析為基礎的減振模式探討…………… 76
5.3.1 吊點參數最佳化設計………………………… 79
第六章：結論與展望 87
6.1結論…………………………………………………… 87
6.2未來展望……………………………………………… 88
參考文獻 90
附錄A A_1
附錄B B_
Acoustical scour monitoring applied to a scale model of Houfeng Bridge
No full text為了能夠利用聲波在水流量大且流速快的狀況下觀察到水下情形，並且做地形上的掃描，論文中以后豐大橋為例，將現地資料縮小成實驗模型比例，並將超音波儀器應用在模型實驗上，來觀察橋墩前的沖刷坑發展。2008年，颱風辛樂克造成后豐大橋p2橋墩倒塌。我們到現地進行測量，結合由各單位所提供的現地資料，設計成模型尺寸。實驗過程中，利用超音波掃描橋墩前的沖刷坑並將影像轉換到正確座標，輸出成三維資料去觀察沖刷坑的變化，再與數值模擬Flow 3D做比較。研究中發現，即使是在濁水狀況下，我們仍可以在影像中看到水下的情況以及顆粒的運動，從照片上所看到的剖面與超音波所抓到的地形變化一致，將掃描資料轉到正確座標後也可以清楚看到橋墩位置與實驗設計吻合。利用聲波，我們可以快速檢視水下情形以及掃描繪成三維地形圖並與現地去做模擬比較。Because of strong flow and high turbidity, it is difficult to observe the scour during floods. To scan river bed under flood, this thesis explores the potential of using acoustical monitoring, applied to a scale model of Houfeng Bridge. In the case of the Houfeng Bridge collapse during the 2008 Sinlaku typhoon, a submerged pipeline upstream of the bridge, led to the undermining of the bridge supports, ultimately leading to its destruction. We transformed field and survey data into a small-scale laboratory experiment. The Sonix ultrasound system was used to view the erosion process ahead of the modeled bridge. The experiment results were compared using flow modeling software, Flow 3D, to verify the laboratory model design. The ultrasound results were presented in a digital terrain model to see changes in the river bed due to erosion. It was found that we could observe the phenomenon in turbid water conditions and capture terrain profiles from ultrasound images. The acoustical camera also provides information about moving stones and structural elements
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