Functional Analysis of the Promoter of Epstein-Barr Virus BBLF2/3

Rta與Zta蛋白質為Epstein-Barr virus (EBV)溶裂期的極早期蛋白質，為轉錄活化子，可以活化早期與晚期基因表現。Rta蛋白質可以直接結合到Rta response element (RRE)上，活化BMRF1、BHRF1、BHLF1與BMLF1等病毒早期基因的表現。另外，Rta也可以形成Sp1-MCAF1-Rta複合體，藉由Sp1結合序列活化自身的表現。Rta蛋白質亦可與Zta蛋白質形成Zta-MCAF1-Rta複合體，結合到啟動子上的Zta response element (ZRE)序列造成協同作用，大量地活化BHLF1、BMRF1與BRLF1等基因的表現。BBLF2/3為EB病毒溶裂期早期基因，可以轉譯出引子酶結合因子 (primase-associated factor)，參與EB病毒溶裂期DNA複製。然而，目前對於Rta與Zta活化早期基因BBLF2/3的機制尚不清楚，因此本研究的目的在於探討Rta與Zta蛋白質對於BBLF2/3啟動子的調控。首先利用冷光酵素分析發現BBLF2/3啟動子可以被Rta活化，同時轉染Rta與Zta蛋白質時會產生協同作用，大量活化BBLF2/3的表現，而Zta蛋白質則無法單獨活化BBLF2/3啟動子。利用TESS網站分析BBLF2/3啟動子，發現該啟動子-74到-80的序列具有可能的AP-1結合序列。將該位置進行點突變後進行冷光酵素分析，發現Rta對BBLF2/3啟動子的活化大幅降低。將BBLF2/3可能的AP-1結合序列接到具有TATA box的pTATA質體進行冷光酵素分析，發現細胞內Rta或ATF2蛋白質的含量越多時，對於該質體的活化能力就越高。另外，以DNA親和沉澱分析證實BBLF2/3啟動子-74到-80的序列可以與ATF2蛋白質結合，而透過凝膠電泳位移實驗也發現Rta蛋白質可以與該序列結合。因此，本篇研究發現BBLF2/3啟動子上具有AP-1結合序列，而Rta蛋白質可以藉由此序列促進BBLF2/3的轉錄。Rta and Zta, two transcription factors expressed during the immediate-early stage of the Epstein-Barr virus (EBV) lytic cycle, are required for lytic activation. Rta activates many EBV early genes, including BMRF1, BHRF1, BHLF1 and BMLF1, through direct binding to Rta response elements (RRE). Rta also enhances SP1-mediated transcription through the interaction with MBD1-containing chromatin-associated factor 1 (MCAF1) and Sp1. In addition, the binding of Rta-MCAF1-Zta complex to Zta response elements (ZRE) activates BHLF1, BMRF1 and BRLF1 synergistically. The EBV BBLF2/3 gene encodes a primase-associated factor that is indispensable for EBV lytic DNA replication. However, the mechanism that activates the transcription of BBLF2/3 remains unclear. The purpose of this study is to elucidate how Rta and Zta activate BBLF2/3 transcription. This study finds that the BBLF2/3 promoter is activated by Rta, but not by Zta. Moreover, Rta and Zta activated the BBLF2/3 promoter synergistically. Sequence analysis from the TESS website predicts that BBLF2/3 promoter contains a putative AP-1-binding sequence, TGACACG, which is located at -74 to -80 in the BBLF2/3 promoter. Reporter assay showed that mutating the site lowers the transcription activity. Meanwhile, Rta and ATF2 activate a promoter in a reporter plasmid, pBBLF2/3-3AP1, which contains three copies of AP-1 site from the BBLF2/3 promoter, in a dose-dependent manner. In addition, ATF2 binds to the AP-1 site as demonstrated by DNA-affinity precipitation assay. Rta also interacts with the AP-1 site as shown by electrophoretic mobility shift assay. Taken together, this study demonstrates that the BBLF2/3 promoter contains an AP-1 binding site from -74 to -80. Rta activates the BBLF2/3 transcription via an indirect binding to the AP-1 site

Robot-Assisted Therapy Combined With Task-Oriented or Impairment-Oriented Training in Chronic Stroke

背景與目的：中風為國人第二大死因，常伴隨動作控制障礙等問題。過去研究顯示，高密集訓練可促進中風病人動作功能恢復。機器輔助治療優點為高密度、高強度、任務專一性與使用方式彈性，但針對特定關節訓練，但對日常生活功能的提升尚無一致性結論。因此，若結合其它復健手法，如：任務導向訓練、損傷導向訓練，則能提供更全面的醫療復健。本研究目的為探討機器輔助療法合併任務導向訓練、機器輔助療法合併損傷導向訓練、常規復建訓練於慢性中風病人之成效比較。 方法：受試者隨機分配到機器輔助治療合併任務導向訓練組、機器輔助治療合併損傷治療訓練組、常規復健組，接受為期4週，每週5天，每天90~95分鐘的療程。 結果：目前結果顯示IMTT在上肢損傷與動作功能、降低肌肉張力、患側手於日常生活使用量、生活品質等方面最具優勢；CI組在近端肌力、日常生活獨立性等方面較有優勢。建議未來研究擴大研究樣本，拉長合併療法時間，進一步探討合併療法於中風復健之成效。Background and purpose: Stroke is the second leading cause of death in Taiwan, usually accompanied by postured control disorder. According to past studies high intensity of training encourages stroke patient’s function recovery. Robot-assisted therapy provides high intensity, task specificity, and higher flexibility of manipulation, but specifically for joint training, and inconsistence with improvement of ADL. Hence, when combine with other approach, such as task-oriented training, impairment-oriented training, provides complete rehabilitation program. This study’s goal is to discuss the effect of robot-assisted therapy and task-oriented training combination, robot-assisted therapy and impairment-oriented training combination, regular rehabilitation training of chronic stroke patients. Methods: patients randomly distributed to IMTT group, IMTI group, and CI group, received an intervention for 4 weeks, 5 days a week, 90~95minutes per day. Results: results shows that IMTT has higher advantages in upper extremity impairment and motor function, decrease of muscle tone, impaired limb usage in daily life, and quality of life; in the other hand, CI has the higher advantage independence in daily life. Suggestion of future study is to enlarge the number of sample, higher duration of intervention, further discuss of the stroke rehabilitation outcome.目次 第一章、 前言 1. 中風 ----------------------------------------------------------------------------------p 1 2. 機器輔助治療 2.1機器輔助治療簡介與分類-----------------------------------------------------p 1 2.2機器輔助治療之特性-----------------------------------------------------------p 2 2.3機器輔助治療之文獻回顧-----------------------------------------------------p 2 2.4 Interactive Motion Technologies 3.0 (InMotion 3.0) 介紹----------------p 3 3. 神經機制探討療效 3.1 單側訓練--------------------------------------------------------------------------p 4 3.2 動作學習理論--------------------------------------------------------------------p 4 4. 任務導向訓練 (Task-Oriented Training, TOT) ---------------------------------p 5 5. 損傷導向訓練 (Impairment-Oriented Training, IOT) -------------------------p 6 5.1 The Arm BASIS training (ABT) ----------------------------------------------p 6 5.2 The Arm Ability training (AAT) ----------------------------------------------p 6 6. 機器輔助治療合併任務導向訓練與損傷導向訓練文獻回顧----------------p 8 第二章、 研究目的與假設-------------------------------------------------------------------p 9 第三章、 研究方法、進行步驟 1. 受試者--------------------------------------------------------------------------------p 10 1.1收案條件-------------------------------------------------------------------------p 10 1.2排除條件-------------------------------------------------------------------------p 10 2. 實驗設計-----------------------------------------------------------------------------p 11 3. 介入方法-----------------------------------------------------------------------------p 11 3.1 機器輔助治療合併任務導向訓練組 (IMTT) ----------------------------p 11 3.2 機器輔助治療合併損傷治療訓練組 (IMTI) -----------------------------p 12 3.3 常規復健組 (C-----------------------------------------------------------------p 13 4. 成效評估-----------------------------------------------------------------------------p 13 4.1 人口學基本資料---------------------------------------------------------------p 13 4.2臨床評估-------------------------------------------------------------------------p 13 4.2.1身體功能與構造層級 (Body function and structure/ impairment) --------------------------------p 13 4.2.2活動層級 (Activities/ Limitation) ------------------------------------p 15 4.2.3參與層級 (Participation/ Restriction) --------------------------------p 15 4.2.4 不良反應 (Adverse effect)--------------------------------------------p 16 5. 資料分析----------------------------------------------------------------------------- p 16 第四章、 結果 1. 受試者------------------------------------------------------------------------------- p 17 2. 臨床評估 2.1 身體構造與功能層級結果--------------------------------------------------- p 17 2.2 活動層級結果------------------------------------------------------------------ p 18 2.3 參與層級結果------------------------------------------------------------------ p 18 2.4 不良反應結果-------------------------------------------------------------------p 18 第五章、 討論 1. 身體構造與功能層級成效 1.1 FMA----------------------------------------------------------------------------- p 19 1.2 MRC----------------------------------------------------------------------------- p 19 1.3 MAS----------------------------------------------------------------------------- p 20 1.4 腕動計--------------------------------------------------------------------------- p 20 2. 活動層級成效 2.1 FIM------------------------------------------------------------------------------- p 20 2.2 WMFT--------------------------------------------------------------------------- p 21 3. 參與層級成效----------------------------------------------------------------------- p 21 4. 不良反應-----------------------------------------------------------------------------p 21 5. 研究限制與未來建議--------------------------------------------------------------p 21 第六章、 結論--------------------------------------------------------------------------------------- p 23 第七章、 參考文獻--------------------------------------------------------------------------------- p 24 第八章、 附錄----------------------------------------------------------------------------------------p3

Deregulation of policies in Japanese-Taiwanese tour bus and related research

[[abstract]]由市場決定供給量，利用政策鬆綁或是廢止，提高企業的活性化與效率化，進而以期獲得更佳的服務品質，是管制開放的目的。台灣從1991年起，對於遊覽車牌照管制逐步開放後，遊覽車的營運車輛數從2500餘輛到2009年的11407輛，成長了約4 5倍。遊覽車公司也激增了約2倍至867家。但由於需求並未隨之同步成長，造成業者相互削價競爭，再加上旅行社業者的低價契約，也降低了營業收入。進而為了降低成本，忽略了車輛及人員的品質。再者，管理法規的不完備，更是助長了靠行經營行為，造成市場秩序的紊亂及行車安全的疑慮。遊覽車是大眾交通工具，其首要的就是行車安全，但近年遊覽車事故卻是不斷發生，引起社會開始關心遊覽車的安全性相關問題。 另外，日本也在2000年開始實施對遊覽車的管制開放，同樣造成市場供需失衡，造成遊覽車業者之間的惡性競爭，引發檢討的聲浪。因此，本研究從遊覽車管制開放的政策面，對台‧日兩國的遊覽車經營、管理型態加以探討，採取文獻回顧與文獻分析法，整理相關研究，釐清台灣遊覽車市場的問題點，以及台灣與日本遊覽車管制開放後的共通點，並依據日本為提高行車安全而實行的遊覽車管理‧檢討政策裡，可供台灣今後施政之參考。 針對台灣遊覽車市場的各項問題，在日本實施的政策裡，可供台灣參考的包括有(1)開放小規模事業加入，以減少靠行車輛數；(2)利用駕駛員雇用條件，以期提高駕駛品質；(3)利用法條約束來禁止旅行社業者壓低遊覽車租金；(4)增加與車輛同等比率的監理監察人員，以落實車輛監察事務；(5)強化行政處分，以期遵守法律；(6)對於政策進行全面性的探討，以求政策的完整性。藉此提供遊覽車的管理與政策之意見，改善遊覽車的行車安全。[[abstract]]The purpose of restricting and releasing quotas in government policies in general is to facilitate business operations with more flexibility rendered since the quantity and quality of the service is being determined by the market demand Since 1991 the licensing restrictions in tour bus in Taiwan have been gradually removed The amount of licensed tour bus in operation has increased from more than 2500 in 1991 to more than 11407 in 2009 with a growth of 4 5 times in between The tour bus businesses have also increased two times to 867 legally registered enterprises However the market demand did not seem to replicate such an increase and the competitions between business entities results forced decrease in operational costs which sacrifice hardware and service quality Furthermore the inadequateness in government regulations further aggravates the existing market structure with little attention being paid to the safety issue Being part of the infrastructure of public transportation safety issue should always be considered as a priority Yet as the car accidents continue to happen in recent years concerns regarding tour bus safety issues have been raised by the general public In 2000 Japan released its restriction to tour bus control and resulted imbalance between market supply and demand The antagonistic competition among businesses led to strong discussions in re-exanimating factors regarding such issue Therefore this thesis aims to discuss the policies related to tour bus regulations in Japan and Taiwan with specific focuses on business operation and administration through literature review and analysis in order to further clarify 1) the problems existed in the tour bus market in Taiwan 2) post-release issues commonly exist in both Japan and Taiwan With experiences drawn from currently implemented tour bus regulations in Japan as a reference we may further review our policies in Taiwan regarding safety maintenance With focuses on existing problems in the tour bus market in Taiwan the following points are drawn from the Japanese policies which may offer us better insights and as references for future policy making 1) Allow small enterprises entering the market rather than businesses with relatively large amount of vehicles 2) Improve the quality of the service through controlling and effectively utilizing driver’s qualifications 3) Restrict unreasonable bargain from travel agencies through government policies 4) Balance the ration between numbers of vehicles and supervisors in order to correctly implement safety check-ups 5) Strengthen law and legal issues Review and discuss policy issues as a whole in order to effectively maintain its functional integrity and effectively improve tour bus administration and operation

回鮭 Salmon Run

[[abstract]]小亮跟著同伴開始了牠的洄游旅程，當牠游出水面時，被船丟下的桶子嚇到拼命地往前游，途中幫助了受困的鮭魚小瑜掙脫，之後牠們一起經歷了許多，最後終於到達小瀑布，然而小瀑布上卻潛藏著更多的危機...

回鮭 Salmon Run

[[abstract]]小亮跟著同伴開始了牠的洄游旅程，當牠游出水面時，被船丟下的桶子嚇到拼命地往前游，途中幫助了受困的鮭魚小瑜掙脫，之後牠們一起經歷了許多，最後終於到達小瀑布，然而小瀑布上卻潛藏著更多的危機...

科技基金與貨幣型基金與大盤指數的連動性-以五家基金公司為例

[[abstract]]此次專題是以投資於科技業之股票型基金以及貨幣型基金與加權指數下去跑迴歸，以二○一一年五月三十日到二○一二年四月三十日，每一日加權指數之點數及兩種基金之淨值下去跑迴歸，藉由研究兩種基金與加權指數的關係。然而，研究發現，股票型基金與加權指數呈相同向的關係，意即加權指數上漲，基金淨值上漲；加權指數下跌，基金淨值下跌，而貨幣型基金則呈現反向關係，意即加權指數上漲，基金淨值下跌；加權指數下跌，基金淨值上漲