Poly(ADP-ribose)polymerase-1 對細胞內DNA damage修補的調控
Poly(ADP-ribose) polymerase-1 (PARP-1)是一個細胞核內的酵素,它可以被因DNA damage\r 而形成的DNA片段活化,並將NAD(+)上的ADP-ribose轉載到結合蛋白質。這些結合蛋白質對\r 於DNA的合成、DNA的修補、以及細胞週期的調控都有關係。因此,PARP-1被認為是維持基\r 因完整性的重要角色。根據初步的研究,抑制PARP-1的活性對許多疾病的治療都可能有效,\r 其中包括癌症、心臟病、中風、糖尿病、發炎以及反轉錄病毒的感染。然而,以藥物抑制一\r 個對DNA修補這麼重要的酵素會有什麼潛在的問題呢?為了要得到解答,我們需要進一步了\r 解PARP-1在DNA damage反應的機能。在這一份報告中,我製造了一個失去活性的PARP-1突變\r 種,即E988K。經過對E988K詳細的研究,我將比較及分析PARP-1野生型與E988K之間不一樣\r 的互動蛋白質,希望能對PARP-1所控制的DNA修補有更進一步的了解。\r \r \r Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme activated by DNA strand breaks\r during DNA damage response and catalyzes the transfer of ADP-ribose units from the substrate NAD(+)\r to acceptor proteins. These acceptor proteins involve in modulation of chromatin structure, DNA\r synthesis, DNA repair, transcription, and cell cycle control. Thus, PARP-1 is believed to play an\r important role in maintaining genome integrity through modulation of protein-protein and protein-DNA\r interactions. PARP-1 has been the target for design of inhibitors for over twenty-five years. Inhibitors of\r the activity of PARP-1 have been claimed to have applications in the treatment of many disease states,\r including cancer, cardiac infarct, stroke, diabetes, inflammation and retroviral infection. However, are\r there potential problems associated with inhibition of this DNA-repair enzyme? To answer this question,\r we need to further understand the biological function of PARP-1 during DNA damage response. In this\r report, an enzyme dead mutant (E988K) of PARP-1 was generated. Detailed studies of E988K show that\r E988K could be used in the following studies. Compare and identify the different associated proteins of\r PARP-1 wild-type and E988K will shed light into the molecular mechanism of PARP-1-mediated DNA\r repair.
口琴簧片振動與氣流的影響
本研究主題在測量口琴簧片受到各種氣流因子影響後,所產生音色、音頻等變化之探討。在過去我們認為,一片簧片不論如何吹奏,其發出的頻率皆相同。但是事實上,演奏家控制氣流的強弱、方向、渦流等,便可吹奏出多樣的音頻。探討形狀因子對簧片頻率的影響,如:長度、寬度、厚度對頻率所造成的影響。自製口琴,利用變壓器控制送風機風速。探討氣流因子對簧片主頻之影響,利用各種不同的自製吹嘴,改變風速、角度、渦流…等,找出可能使簧片改變頻率的氣流因素。實驗結果發現改變風速會影響簧片主頻的變化,風速越大,頻率越大,為一條平滑線。但並非一直都會上升,當簧片頻率上升至某一極限,便無法再利用風速使頻率上升。例如實驗四吸音標準狀態下,風速大於8 Kt 後,頻率一直停在429Hz。在外加障礙物時(模擬吹奏舌頭時隆起)和標準狀態(正常零度入射)下頻率比較吹音和吸音有明顯的差異。吹音時,同風速下,其頻率比標準狀態高,發生音升;吸音時,同風速下,其頻率比標準狀態低,發生音降,具應用性。我們發現在頻率改變時,簧片的振動型態會有所不同,所以利用高畫素像機拍攝和電腦相位差算出簧片之曲折點至尾端的距離,發現頻率和簧片之曲折點至尾端的距離成正向關係。如實驗五中頻率從414 至419Hz,簧片的曲折點到振動端距離也明顯變大。我們發現吹嘴和口琴只要稍有一點空隙(大約在0.2cm 左右),便會和完全吻合時有顯著的頻率差距(吻合後大約比有空隙低20Hz 左右),此實驗頻率變化現象和現實壓音頻率變化極為相近。實驗過程中發現,改變簧片吹嘴的吻合程度,吹入口琴的風速相近,但頻率變化卻也有壓音的音頻變化。在實驗三加入各種氣流因子發現入射角度和標準情形差異不明顯,因此推論壓音的頻率變化和風力強度、入射角度關係不大,壓音主要為渦流所造成的現象。簧片振動模式改變,導致簧片振動頻率發生變化,且簧片的自然頻率不變。當壓音產生時,氣流在振動面造成妨礙簧片振動的抗力,但琴格內部同時也給簧片的風壓,使簧片產生一種非自然振動的頻率。The theme of the research is to explore the changes on its timbre and frequency after the harmonica reed is influenced by each kind of air current factor .In the past ,most people think no matter how to play the reed ,the frequency it produced was supposed to be the same. But in fact the frequency will be changeable under different direction, turbulent flow and air intension by the perform. First to explore the basic feature of harmonica reed, for example: The length, the width, thickness cause the influence on the frequency. To make the self-made harmonica, using the transformer control air feeder wind speed. To discussion the influenced caused by air current factors,and use each kind of different self-restraint to boast, change the wind speed, angle, turbulent flow ,in order to discover possible factors the reed causes to change the frequency of the air current factor. The experimental result discovered the change of wind speed can affect the change of basic frequency , the stronger speed cause the bigger frequency, It will be a curve. But it will not be rising continuously, when the reed frequency rise to some limit, it is unable to cause the frequency rise again by using the wind speed. For example experiment four sound absorption standard conditions, after the wind speed is higher than 8 Kt, the frequency continuously stops in 429Hz. To compare obstacle (simulation plays when tongue sticks out) and the standard condition (normal zero degree incidence) , comparison blows the sound agreement sound absorption to have the obvious difference. When blows the sound, under the same wind speed, its frequency is higher than the standard condition, has the sound to rise; When sound absorption, under the same wind speed, its frequency is lower than the standard condition, has the sound to fall. The harmonica terminology for presses the sound, extremely has the application. We discovered when frequency change, the reed vibration condition have differently, therefore use the camera photography and the computer phase different figures out the reed winding point to the end distance, discovered the frequency and the reed winding point relate to end distance is being connected. If tests five medium frequencies from 414 to 419Hz, the reed winding point is away from to the vibration end also obviously changes . The different reed vibration condition cause the frequency to change. Natural frequency is constant. When cause “bending” (the frequency is lower than the standard condition), the airflow make a force keep from reed vibration. But the chamber air pressure still drive reed. therefore cause the reed to give off not natural frequency sound
無尾翼飛行器之穩定與控制
無尾翼飛行器(Tailless Aircraft)在軍事上的價值極大,且對於目前正在起步的微飛行載具(Micro Air Vehicle)而言,亦是值得嘗試與投資的。然而,由於無尾翼飛行器缺乏用以平衡的水平尾翼,造成其靜態的不穩定,即使設法提高靜態穩定特性,但其氣動力阻尼低、穩定性仍舊不佳。操縱上更是困難,在飛行穩定性與控制系統設計上極其挑戰性。本研究目的在探討無尾翼飛行器之穩定性與控制技術,改善其先天之不穩定特性,考慮之項目有縱向靜態穩定性、動態穩定性、控制面與組件配置等因素等進行詳細之探討。首先,找出了適用於無尾翼飛行器之Reflex翼形,接著建立無尾翼飛行器之非線性縱向動態模式,然後針對一翼展8Ocm之小型飛行器進行外型設計,並觀察分析其實際飛行狀態,再以理論與經驗公式估算無尾翼飛行器之氣動力導數,探討其飛行穩定與操控性能。此外,並運用古典控制PID控制法則,設計控制器進行非線性受控系統之動態響應模擬。由模擬結果可看出,經由翼剖面改變與控制系統的輔助下,大幅提高了其性能,使得無尾翼飛行器克服了先天的不穩定特性,更提高了其發展空間 The tailless aircraft has a great value on the military use. Meanwhile, it is worthwhile to try and to invest in it for the investigation of MAV(Micro Air Vehicle), which is being developed now. However, because of lacking horizontal tail which is used for balance, the tailless aircraft is static unstable. Even with the attempt to enhance its characteristics of static stability, the stability of the tailless aircraft is still poor for the sake of it's low damping in aerodynamics. Therefore, it is a challenge to flight stability and control system designing. The purposes of this research are to study the stability and the control technique of the tailless aircraft. To improve its congenital lacking of stability, thought over the longitudinal static stability, dynamic stability and control system. First, find the "Reflex" airfoil is suitable for the tailless aircraft. Second, set up a non-linear and longitudinal dynamic model of the tailless aircraft. Third, design an 80cm span small airplane. Hence, observe and analyze its flying condition. Finally, utilize the theoretical and experiential equations to estimate the aerodynamic derivatives and investigate its stability and controllability. Besides, use the PID controller to proceeded the time-response simulation of the non-linear system. The result of simulation shows that the performance is improved through the change of the airfoil and with the auxiliary of the control system. With this improvement, the tailless aircraft overcome the congenital lacking of stability to broaden its utilization potential.
你喝下了多少?-台灣市售優酪乳乳酸菌生長力及抗酸性之探討
現今乳酸菌飲料風行,但是乳酸菌是否真能通過胃酸的考驗,到達腸道進行複製,利益人體?我們首先以市售乳酸菌粉(加拿大Rosell 公司,含二種菌,暫時命名為"小毛"及"小白")為預測菌種,利用分光光度計測定乳酸菌於Thioglycollate 培養基中的生長能力(OD600)。小毛在pH 值 1、 3 、5、 7 時之生長力分別為0、 0.008 、0.682 、0.847 ,小白為 0、 0.015 、0.973、 0.636。若於培養基中添加不同濃度的螺旋藻熱分解物,如加入0.01%的添加物後,小毛在以上各種pH 值生長力分別為0.042、1.291, 、1.447, 、1.213 ,小白為 0.053、1.392、 1.531、 0.988,意外發現可大幅提升菌的生長力及抗酸力。再取台灣市售4 種廠牌優酪乳(以甲、乙、丙、丁代表之),分離乳酸菌,再於各種pH 值中培養。結果在pH 3 時,螺旋藻熱分解物僅對丙廠牌有效, 乙廠牌無效, 甲與丙則有無填加生長力都很差。在pH 1 時, 則對乙、丙、丁皆有效,故建議廠商慎選菌種,並於製程及成品中添加螺旋藻熱分解物。The yogurt is a popular drink. But whether the lactobacilli inside can resist the destruction of gastric acid and grow well in the intestinal tract is still questionable. We used pure lactobacilli powder (Rosell Company, Canada, containing two bacteria named in this report as "Little Hair" and "Small White") for pre-test. The growth ability in thioglycollate medium was determined by spectrophotometer (OD600). The results of bacterial growth at pH 1, 3, 5, and 7 for "Little Hair" were 0, 0.008, 0.682, and 0.847, respectively. Those for "Small White" were 0, 0.015, 0.973, and 0.636, respectively. After supplement with 0.01% of the boiled lysate of Spirulina algae (ProBio Biotech, Taiwan), growth abilities at pH 1, 3, 5, and 7 for "Little Hair" were 0.042, 1.292, 1.447, and 1.213, respectively. Those for "Small White" were 0.053, 1.392, 1.531, and 0.988, respectively. The algae extract amply promotes the growth and acid-resistance, especially at pH 3, of these bacteria. The lactobacilli isolated from four different products of yogurt in Taiwan, named as A, B, C, and D, were then tested as above. Results showed the supplement with the boiled lysate of Spirulina algae was very effective, at pH 3, for promoting growth of C, but not effective for B. Growth abilities of both A and D were very unsatisfactory with or without this supplement. At pH 1, algae lysate supplement significantly improved the growths of B, C, and D. Therefore, this supplement in culture and product for yogurt preparation was suggested.
關於渦旋
A professor once told me that scientists have already known a lot about vortices, but less about how to tackle with them in here and there cases. As to my mind, this means knowing by halves. As a matter of fact, I gradually found that human may not know more than a dragonfly! A dragonfly flying in a figure of eight pattern does know about Vortices Recycling. The highlight of the experiment is the hovering ability upon a fixed point in the air. Who can stay longer will be the king of Vortices. Sometimes I am not so optimistic about mimicking a fly or a bat, but I am really very interesting in discovering which flying mechanism is more effective,『Fling Mechanism』 or 『In a figure of eight pattern』, if with the same weight and energy? How to implement their mechanism in our flying machine? It is always the best policy to do naturally with vortices. The conservation of vortices is found here and there. Vortex itself is energetic. To gain means to keep. The one who is able to keep vortices will be rewarded. As in life generation and the ability of hovering, the rule follows. Typhoons and tornados still threat us like the beasts. And what’s more, a jumbo-airplane was crashed as beaten by tip vortices of the former airplane. As the dragonflies, the beautiful acrobats of vortices , infuse in tip vortices. Not the strong contradistinction did we realize that it is time for vortices!研究渦旋已經四年。四年之中,涉獵了許多關於渦旋的實驗。當我越了解渦旋,就越佩服那些卓越的昆蟲朋友們,他們可說是調配利用渦旋的大師。從候鳥遷徙的V字型隊伍、海豚的渦旋氣球、到蜻蜓八字型的飛行機制,我很想知道:在一個固定的流場中,到底哪一種運動機制,能最有效率的提供上升的力量?而如何將昆蟲朋友們的高超技術,運用到人類飛行載具上?將是我有興趣的另一項課題。『關於渦旋』是一系列渦旋實驗,目的就是自基礎開始深入了解在地球這樣環境下渦旋的性質。(一)探討基礎的渦旋本質(二)產生相對運動下物體的的渦旋架構(三)物體取得升力和失去升力的要件(四)昆蟲飛行機制探密(五)未來展望與渦旋的運用經過長時間的觀察可以了解到:1、渦旋遵守動量守恆。是以渦旋出現時是成對的2、渦旋是具有能量的。在上升力取得方面,當攻角過大時,渦旋剝離,造成能量的損失;以至於飛行載具失速。而蜻蜓是保有渦旋並加以利用的高手,自然事半功倍。順勢而為,渦旋增強。
「從害羞到大方需要多少時間」(環境因子對含羞草開葉時間的影響)
含羞草會因為受到各種不同外界刺激(光照、外力等等),而造成膨壓改變。外 觀上表現出葉片閉合或有葉柄下垂的現象。其中含羞草處在黑暗的環境下一段時 間後,會做出睡眠運動。當它重新暴露於光照之中,將會需要一段時間以恢復原 先葉片張開的樣子。這個實驗是研究不同類型的環境因子(主要是光照和溼度)在打 破睡眠運動之後,對其葉片復原時間所造成的影響。我們針對上述環境因子在不 同狀況時,進行我們的實驗上百次,進一步得到了多項的數據。也在實驗中,為 了精確了解整個恢復的程序,而將恢復程序程序做成書面說明。以下是我們所紀 錄與分析完數據後的結果,以及我們在實驗期間,進行一些不同的實驗嘗試,所 發現不同於表面所見的驚人事實。 The mimosa can accept plenty of stimulation (light, force, etc), which results in the change of turgor pressure, and on outward appearance, it shows the phenomenon that the leaves become closed or that the stalks get pendent. Among the stimulation, the mimosa will undergo nyctinasty when it is left in the dark for a period of time, in order to enable it to be exposed to the light once more, which requires certain time. This experiment is based on how different kinds of elements of the environment (primarily light and hydro level) effects the rehabilitation time after the nyctinasty is broken. A large number of data are gained after experimenting on it for hundreds of times. Steps of habilitation are also made into illustration in writing, so as to understand the whole steps accurately in the experiment. Below are our records and analysis based on the data, including a few special experimental tries during our working time, in which some surprising facts that were discovered are different from what are seen on the surface.
免疫治療的新展望:從一個疾病的動物模式,探討樹突狀細胞的培養與分析
胰島素依賴型糖尿病(insulin-dependent diabetes mellitus; IDDM)是一種胰島素無法正常分泌的自體免疫疾病;而NOD老鼠(non-obese diabetic mouse,NOD)的病徵與其非常相似。藉由觀察NOD老鼠發病前後外顯行為及疑導組織切片的差異,我們認為胰島素依賴型糖尿病的致病機轉是因為T細胞工及胰島組織中製造胰島素的β細胞,使胰島素分泌不足而引起糖尿病;而樹突狀細胞(dendritic cell,DC)是調控淋巴細胞反映的重要調節細胞,未來可望利用樹突狀細胞進行胰島素依賴型糖尿病的免疫調控治療。本實驗即是利用IL-4、GM-CSF使NOD老鼠的骨隨幹細胞分化樹突狀細胞,並藉由控制NOD老鼠的年紀與的數突狀細胞培養天數,希望取得較多的數突狀細胞,以利未來免疫治療之用。Insulin-dependent diabetes mellitus (IDDM) is a spontaneously occurring autoimmune disease in which cellular immune components mediate destruction of the insulin-producing βcells of the pancreas. It begins with an asymptomatic stage during theβcells are gradually destroyed. These patients have to depend on injecting insulin to lower their blood glucose, facing the dander of being infected. So we want to research into the cause of IDDM by model animal- NOD mouse (non-obese diabetic mouse). We observe the differences of exterior behavior and sections of pancreas organization between NOD mice and normal ones. It has been shown that the immunophological mechanism of IDDM is T cells destroy βcells of genetically predisposed individuals and result in insufficiency of insulin-producing. Dendritic cells(DC), having great Ag-presenting ability, are related to IDDM. We cultivate bone marrow stem cells of 5-week-old,8-week-old, and 21-week-old NOD mice treated with IL-4,GM-CSF and make them differentiate into dendritic cells. The result shows that using 8-week-old NOD mice to cultivate will get the largest amount of dendritic cells. We also compare the percentage of differentiated DCs for 6 days’ culture with 9 days’,and we find that 9 days’is better. Dendritic cells are the effect Antigen-presenting cells which can be used for immunotherapy of IDDM , though , its complicated mechanism still needs further researching and developing. We hope in the future IDDM patients could get rid of the suffering of injecting insulin in their whole life.