路燈巡修作業的落實與否，影響路燈維護的效率及品質，為能有效提升路燈管理之效能，近來管理階層逐漸重視路燈巡修區域的規劃。然而巡修區域的劃分，多依據主管人員之經驗調派，缺乏系統化、科學化的分析與評估，往往使人力資源無法有效運用，形成勞逸不均的現象，進而影響維護品質，因此如何以科學的方法劃分路燈巡修區域是個重要的課題。 本研究的重點在於針對現行路燈巡修區域劃分之缺點，提出一個新的方法，使各區域管理員巡修時間差達到最小化，以解決現行區域劃分的不合理現象。我們所提出的劃分法，以基因演算法進行演算，並加入禁忌名單改善基因演算法區域搜尋效率不佳的缺點，提升整體的求解速度，同時將路燈維護數量、故障率、維護時間、交通時間、巡修次數等影響因子，納入巡修時間的計算公式中，使劃分後各區的巡修時間差達到最小化。 本研究以台北市政府公園路燈工程管理處的路燈東區分隊為實作對象，在考慮不同的基因演化條件下，分別比較巡修區域劃分前後之變化情況，由實驗結果顯示，我們提出的劃分方法，確實使各區管理員的巡修時間差不超過3%，並且滿足巡修不跨區作業之需求。 / The efficiency and quality of street lights maintenance is influenced by the operation of patrolling and maintaining. In order to raise the working efficiency of maintenance crew, the supervisors pay more attention to region redistricting recently. The formor region districting methods normally base on human experiences without systematic or scientific evaluations, These facts, not only result in human resources wasting and uneven labor allocations, but also affecting the maintenance qualities. Therefore, it is a crucial issue to make region redistricting more scientifically. The key point of this research is to provide a systematic redistricting mechanism to minimize the patrolling time variation for all the districts. Our mechanism is based on genetic algorithm to reduce the patrolling time differences. Tabu search list is used to improve the searching efficiency of general genetic algorithms. Various factors were integrated in our mechanism to minimize the patrolling time variations. These factors include total number of street lights, average failure rate, average maintenance time, traffic delay, patrolling and maintaining frequency, etc. We used districts covered by the East Branch of SET/PSO of Taiepi City Government as the examples in our studies. The experimental results show that, using our mechanism, the patrolling time difference is reduced to 3% and maintenance crews can perform their duty without crossing region boundary.

近年來全球在生物科技上發展迅速，尤其是其中農業科技部分之基因改造作物的發展，更對於消費者、農民和農業發展造成不小衝擊。且就我國生技產業而言，由於國外生物科技產業之發展已遠遠超過我國現今之發展，為提高產業之競爭力，實有必要選擇具備競爭優勢的項目，將研發、生產、資金能力集中於這些項目上。而在生物科技之眾多領域中，我國在生物科技各產業中最具發展潛力的即為農業生物科技下之基改作物產業，因此就此方面之相關法規建構應加以重視。 基因改造作物之快速發展一方面雖帶給人類社會許多創新的福祉與商機，但也同時引發了許多不同型態的社會議題與科技風險。而在基因改造作物之所有相關爭議問題中，最重要的即集中在「相關智慧財產權之保護」與「安全之管理」兩者上，而這也是本論文主要之重心所在。對於農民來說，影響最深之為基改作物相關技術的智慧財產權化，相關重要案例如本論文第四章第二節中所探討之Monsanto Co. v. McFarling案與Schemeiser v. Monsanto案。對於消費者而言，由本論文第三章可知基因改造作物所帶來之利益與潛藏危機並存，因此在發展基因改造作物，享受其優點之同時，對於基因改造作物之管理則更突顯出其重要性。而對於基因改造作物之管理制度，各國採取不同之立場，尤其是美國與歐盟更可說是採取相對立之立場態度，而經由分析可知其採取不同立場係由於歐盟消費者對於基改作物產品之食用接受度較低、社會大眾著重生態環境保護之程度較高，以及基因改造作物在歐、美之個別不同農業生產環境下所擁有之優勢不同，而因此所帶來之經濟效益有所落差所致。因此透過對於歐、美制度之檢討，本論文在我國制度之制訂上，即針對我國消費者對於基改作物產品之食用接受度、我國社會大眾對於生態環境保護之關心程度，以及基因改造作物在我國農業生產環境下所擁有之優勢等因素加以探討。

在音樂中，組曲是一種特別的創作形式。組曲將多首音樂段落組合排列，並且在音樂段落之間加入間奏，形成一首音樂組曲。組曲的編曲重點在於音樂段落的編排順序及段落之間的連結。平時在宴會、舞會、餐廳、賣場等場合中，往往都會連續播放多首流行音樂。利用電腦編曲自動產生流行音樂組曲，將可提升播放音樂的銜接與流暢感。 因此，本研究利用資料探勘技術及音樂編曲理論，將多首音樂重新改編成一首組曲。系統首先將每首音樂分段並找出每首音樂的代表段落。接著，系統根據代表段落間的相似度編排順序。最後，為了達到組曲中音樂段落連接的流暢性，我們以模型訓練的方式在段落連結間加入間奏。系統從訓練資料學習產生旋律發展、和弦進程與節奏的模型，接著分析代表段落的動機、旋律、和弦及節奏，使得組曲編曲後的段落連結更為流暢且完整。本研究以流行音樂鋼琴伴奏曲為測試資料，我們分別邀請三十四位受過音樂訓練與未受音樂訓練的測試者，針對本研究所提出的鋼琴伴奏節奏辨識、代表段落萃取、段落順序編排及間奏產生，評估其效果。實驗結果顯示，本研究所提出的順序編排與間奏產生技術，對於組曲的流暢感，有著相當大的幫助。 / In music, a medley is an organized piece composed from segments of existing pieces. Ordering and bridge for connection between segments are the important elements for medley arrangement. Automatic medley arrangement is helpful for playing a set of music continuously which is common in banquet, party, restaurant, shopping mall, etc.. This thesis aims to develop the automatic medley arrangement method by using data mining techniques and music arrangement theory. The proposed method first segments each music and discovers the significant segment from each music. Then, the linear arrangement based on the similarities between significant segments is generated. Finally, in order to connect segments smoothly in the medley, the bridge between two segments is generated and inserted by using model training. Three models, melody progression, chord progression and rhythm models are learned from training data. For the experiments, testing data is collected from popular piano music and thirty-four people are invited to evaluate the effectiveness of the rhythm recognition of accompaniment, the extraction of significant segment, the linear arrangement of segments, and the creation of bridge. Experimental results show that the proposed medley arrangement method performs well.

如何藉由DNA微陣列資料跟存活資料的資訊來找出基因表現定型一直是個重要的議題。這些研究的主要目標是從大量的基因中找出那些真正跟存活時間或其它重要的臨床結果有顯著關係的小部分。Threshold Gradient Directed Regularization (TGDR)是ㄧ種已經被應用在高維度迴歸問題中能同時處理變數選取以及模型配適的演算法。然而，TGDR採用一種梯度投影型態的演算法使得收斂速率緩慢。在本篇論文中，我們建議新的包含Newton-Raphson求解演算法類型的改良版TGDR方法。我們建議的方法有類似TGDR的特性但卻有比較快的收斂速率。文中並利用一筆附有設限存活時間的真實微陣列癌症資料來做示範。 本篇論文的第二部份是關於適用於區間設限存活資料的重複抽樣Peto-Peto檢定。這個重複抽樣Peto-Peto檢定能夠評估存活函數估計方法的檢定力，例如Turnbull的估計方法以及Kaplan-Meier的估計方法。這個檢定方法顯示出在區間設限資料時Kaplan-Meier的估計方法的檢定力要比Turnbull的估計方法的檢定力來得低。這個檢定方法將以模擬的區間設限資料以及一筆真實關於乳癌研究的區間設限資料來說明。 / Analyzing censored survival data with high-dimensional covariates arising from the microarray data has been an important issue. The main goal is to find genes that have pivotal influence with patient's survival time or other important clinical outcomes. Threshold Gradient Directed Regularization (TGDR) method has been used for simultaneous variable selection and model building in high-dimensional regression problems. However, the TGDR method adopts a gradient-projection type of method and would have slow convergence rate. In this thesis, we proposed Modified TGDR algorithms which incorporate Newton-Raphson type of search algorithm. Our proposed approaches have the similar characteristics with TGDR but faster convergence rates. A real cancer microarray data with censored survival times is used for demonstration. The second part of this thesis is about a proposed resampling based Peto-Peto test for survival functions on interval censored data. The proposed resampling based Peto-Peto test can evaluate the power of survival function estimation methods, such as Turnbull’s Procedure and Kaplan-Meier estimate. The test shows that the power based on Kaplan-Meier estimate is lower than that based on Turnbull’s estimation on interval censored data. This proposed test is demonstrated on simulated data and a real interval censored data from a breast cancer study.

人類隨著年齡增長後中樞神經系統的修補及再生能力逐漸下降，一旦神經系統受到傷害，是很嚴重的問題。因此，引導或促進神經細胞生長甚至再生的方法，中樞神經受損患者將獲得更有效的治療。先前已有文獻指出由植物厚朴萃取的天然化合物─和厚朴酚，具有抗氧化、抗腫瘤、抗發炎、神經保護與滋養的作用。在不同疾病模式的囓齒動物實驗，如帕金森氏症、阿茲海默症、癌症與腦缺血疾病等，和厚朴酚皆具有預防疾病或減緩症狀的效果。本篇研究使用和厚朴酚之衍生物─新合成雙酚化合物(MH102、MH103、MH104、MH106、MH107與MH111)，並探討對於神經細胞的保護與滋養作用。透過腎上腺髓質嗜鉻細胞瘤 PC12 細胞預先處理新合成雙酚化合物，並以過氧化氫(H2O2)使細胞產生氧化壓力，使用活性氧檢測試驗(DCFH-DA assay)偵測細胞內活性氧(reactive oxygen species, ROS)的含量。實驗結果顯示，預先處理較高濃度(3-10μM)的新合成雙酚化合物顯著降低過氧化氫所產生的氧化壓力。另以H2O2誘導PC12細胞死亡，並使用MTT試驗法，觀測新合成雙酚化合物對於細胞存活的影響。結果顯示新合成雙酚化合物顯著減少H2O2造成的細胞死亡。於神經滋養實驗，發現新合成雙酚化合物無法直接誘導PC12細胞的神經突生長。因此，使用神經滋養因子(nerve growth factor, NGF)誘導PC12細胞神經突生長，發現新合成雙酚化合物在低濃度(0.1-0.3μM)顯著加強神經突生長。然而雙酚化合物加強NGF誘導神經突生長之機制，並非透過活化細胞外信號調節激酶 (extracellular-signal-regulated kinases, Erk1/2)與訊息傳遞轉錄活化基因-3 (signal transducer and activator of transcription 3, STAT3)，Erk1/2的活化在短時間內(5至10分鐘) 反而減少，STAT3的活化則沒有差異。由此推論，新合成雙酚化合物的保護作用是透過減少ROS的產生，並可以加強NGF對於PC12細胞的神經突生長，但不是透過Erk1/2或STAT3路徑所致。

STAT1是一個轉錄因子，在細胞生理功能中是非常重要的訊息傳遞者，在免疫系統具有抗病毒的角色，但是目前為止對於STAT1在中樞神經系統所扮演的角色仍不清楚。爲證實STAT1的表現與空間記憶的形成有關聯，我們將大白鼠分成兩組，一組為有訓練的組別，另一組則為無訓練的組別分別進行水迷津試驗，試驗完畢後取出大鼠的海馬迴CA1區域組織進行即時定量聚合酶連鎖反應與西方墨點法分析。結果顯示，經過水迷津訓練的刺激下，STAT1 mRNA與蛋白質分別減少約34 %及40 %，而STAT2 mRNA及蛋白質的表現則不受空間學習的影響。爲了進ㄧ步探討STAT1在空間學習記憶過程中所扮演的角色，實驗利用STAT1 siRNA轉染至海馬迴CA1區域抑制STAT1的表現，發現降低STAT1表現會促進大白鼠在水迷津試驗的學習能力，實驗同時也轉染STAT2 siRNA至CA1區域，結果顯示STAT2不參與大白鼠空間記憶的形成。本實驗室先前發現降低laminin β1表現量會促進大白鼠的空間學習記憶 (unpublished observation, 附錄二)，此外laminin β1基因啟動子上具有STAT1結合序列：interferon-γ activated site (GAS)。因此，實驗利用PC12細胞進行laminin β1報導基因分析，結果顯示STAT1會促進 laminin β1啟動子的轉錄活性。而爲了進一步探討在STAT1影響空間學習與記憶歷程中與laminin β1的關聯性，實驗利用STAT1 siRNA抑制大白鼠海馬迴CA1區STAT1的表現並促進空間學習與記憶的同時，發現laminin β1 mRNA及蛋白質表現量都受到STAT siRNA的抑制，而轉染野生型STAT1-Flag質體則會增加laminin β1 mRNA及蛋白質的表現量，顯示STAT1正向調控laminin β1的表現。本篇論文提出海馬迴CA1區域的STAT1參與動物空間學習與記憶的形成，其中可能與STAT1正向調控laminin β1的表現有關。 / STAT1 is a signal transducer and transcription factor in the cell. Several reports have indicated that STAT1 plays a critical role in immune response against virus infection in animals. However, the role of STAT1 in the central nervous system is still unclear. In the present study, we aimed to examine the role of STAT1 involved in spatial memory formation in rat and the possible downstream gene that STAT1 regulates. Rats were randomly divided into the trained group and the non-trained group. Animals were subjected to water maze learning according to the previous behavioral paradigm. Their hippocampus CA1 tissues were dissected out for STAT1 mRNA level and protein level determination. Results indicated that spatial training markedly decreased STAT1 mRNA level and protein level in the CA1 area, but this change was not found for STAT2 mRNA and protein expression. To further confirm the role of STAT1 involved in spatial learning and memory, animals were transfected with STAT1 siRNA in the CA1 area. Results showed that STAT1 siRNA transfection significantly facilitated water maze performance, whereas their water maze performance under STAT2 siRNA transfection was not altered. Previous studies from our laboratory have demonstrated that laminin β1 impairs spatial memory formation in rat (unpublished observation). In addition, promoter analysis indicates that the laminin β1 promoter region contains two GAS elements, which is the STAT1/STAT1 and STAT1/STAT3 binding site. Results from luciferase reporter assay revealed that transfection of STAT1 siRNA decreased laminin β1 promoter activity, whereas transfection of STAT1 wild-type plasmid increased laminin β1 promoter activity. To further study the relationship between STAT1 and laminin β1 in spatial memory formation, we used STAT1 siRNA to knockdown STAT1 expression and these animals were subjected to spatial training. We then determined their laminin β1 expression. Results showed that the laminin β1 mRNA level and protein level were both significantly decreased by STAT1 siRNA transfection. Besides, STAT1 wild-type plasmid transfection increased laminin β1 mRNA level and protein level in the CA1 area associated with spatial memory impairment. These results together suggest that STAT1 negatively regulates spatial memory formation. Further, STAT1 may impair spatial memory formation through increased laminin β1 expression.

The CUSUM control charts have been widely used in detecting small process shifts since it was first introduced by Page (1954). And recent studies have shown that adaptive charts can improve the efficiency and performance of traditional Shewhart charts. To monitor the process mean and variance in a single chart, the loss function is used as a measure statistic in this article. The loss function can measure the process quality loss while the process mean and/or variance has shifted. This study combines the three features: adaption, CUSUM and the loss function, and proposes the optimal VSSI, VSI, and FP CUSUM Loss chart. The performance of the proposed charts is measured by using Average Time to Signal (ATS) and Average Number of Observations to Signal (ANOS). The ATS and ANOS calculations are based on Markov chain approach. The performance comparisons between the proposed charts and some existing charts, such as X-bar+S^2 charts and CUSUM X-bar+S^2 charts, are illustrated by numerical analyses and some examples. From the results of the numerical analyses, it shows that the optimal VSSI CUSUM Loss chart has better performance than the optimal VSI CUSUM Loss chart, optimal FP CUSUM Loss chart, CUSUM X-bar+S^2 charts and X-bar+S^2 charts. Furthermore, using a single chart to monitor a process is not only easier but more efficient than using two charts simultaneously. Hence, the adaptive CUSUM Loss charts are recommended in real process. / The CUSUM control charts have been widely used in detecting small process shifts since it was first introduced by Page (1954). And recent studies have shown that adaptive charts can improve the efficiency and performance of traditional Shewhart charts. To monitor the process mean and variance in a single chart, the loss function is used as a measure statistic in this article. The loss function can measure the process quality loss while the process mean and/or variance has shifted. This study combines the three features: adaption, CUSUM and the loss function, and proposes the optimal VSSI, VSI, and FP CUSUM Loss chart. The performance of the proposed charts is measured by using Average Time to Signal (ATS) and Average Number of Observations to Signal (ANOS). The ATS and ANOS calculations are based on Markov chain approach. The performance comparisons between the proposed charts and some existing charts, such as X-bar+S^2 charts and CUSUM X-bar+S^2 charts, are illustrated by numerical analyses and some examples. From the results of the numerical analyses, it shows that the optimal VSSI CUSUM Loss chart has better performance than the optimal VSI CUSUM Loss chart, optimal FP CUSUM Loss chart, CUSUM X-bar+S^2 charts and X-bar+S^2 charts. Furthermore, using a single chart to monitor a process is not only easier but more efficient than using two charts simultaneously. Hence, the adaptive CUSUM Loss charts are recommended in real process.

阿茲海默症是一種隨著年齡老化有關的神經退化性疾病，其特徵主要為記憶喪失及認知功能失調。阿茲海默症有兩個主要的病理指標，包含了因為濤蛋白造成的神經纖維糾結以及乙型類澱粉蛋白堆積而成的老化斑塊。乙型類澱粉蛋白是由類澱粉前驅蛋白經β-分泌酶及γ-分泌酶連續裁切生成大小約4-kDa的胜肽。乙型類澱粉蛋白會相互堆積形成寡聚體，並且高分子量寡聚體進一步再堆積成不可溶性的乙型類澱粉蛋白纖維及老化斑塊。半乳糖凝集素-3是半乳糖凝集素家族的一員，目前已知半乳糖凝集素-3調節各種細胞的功能，例如發炎、腫瘤生長以及細胞間的黏附，而在癌症中則有促使癌細胞積聚的能力，然而在大腦中的作用仍尚不清楚。在本研究中，我們使用APP/PS1基因轉殖小鼠作為阿茲海默症的動物模型，並且在其大腦中研究半乳糖凝集素-3對於乙型類澱粉蛋白堆積的作用與機制。結果顯示在野生型小鼠的海馬迴中過度表現半乳糖凝集素-3會促進乙型類澱粉蛋白的堆積，而將乙型類澱粉蛋白注射在半乳糖凝集素-3基因剔除小鼠的海馬迴，則會觀察到乙型類澱粉蛋白寡聚合作用的減少。乙型類澱粉蛋白的注射也會增加海馬迴中半乳糖凝集素-3的表現。在APP/PS1小鼠的海馬迴可以觀察到半乳糖凝集素-3的表現量會隨著年齡增長而增加，而具有抑制發炎及免疫反應的PIAS1在APP/PS1小鼠海馬迴中的表現量則會隨著年齡增長而減少。在探討半乳糖凝集素-3調節乙型類澱粉蛋白寡具體作用的過程中，我們發現半乳糖凝集素-3基因剔除小鼠的海馬迴中能夠代謝乙型類澱粉蛋白的腦啡肽酶表現量是野生型小鼠的兩倍多。研究結果顯示半乳糖凝集素-3對於乙型類澱粉蛋白的堆積扮演了重要的角色以及可能在阿茲海默症的病理機制中具有重要的作用。 / Alzheimer’s disease (AD) is an age-related neurodegenerative disorder which is characterized by progressive loss of memory and other cognitive functions. The two pathological hallmarks of AD are extracellular amyloid plaque and flame-shaped neurofibrillary tangles of the tau protein. Aβ is a 4-kDa protein that is resulted from sequential cleavage of the amyloid precursor protein by beta-secretase and gamma-secretase. Once Aβ is produced, it will aggregate to form oligomers and high molecular weight (HMW) oligomers will further assemble to form large insoluble fibrils and plaque. Galectin-3 (Gal-3) is a member of the β-galactoside-binding galectin protein family. Gal-3 is known to regulate various cellular functions, such as inflammation, tumor progression and cell-cell adhesion. In cancer cell, Gal-3 enhances homotypic aggregation, but its role in the brain is much less known. In the present study, we examined the role and mechanism of Gal-3 in Aβ aggregation in the brain by adopting the APP/PS1 mice as an animal model of AD. Results revealed that overexpression of Gal-3 enhanced Aβ oligomerization, whereas Aβ injection into hippocampus of Gal-3 KO mice reduced Aβ oligomerization. Aβ injection also increased Gal-3 expression in the hippocampus. Gal-3 expression is also increased in APP/PS1 mice and this effect is more significant along with ageing. Meanwhile, the expression of protein inhibitor of activated STAT1 (PIAS1) that suppresses inflammation and immune response was decreased with ageing in APP/PS1 mice. We further found that the expression level of neprilysin, an enzyme that degrades Aβ, was increased for approximately two-folds in Gal-3 KO mice compared with WT mice. These results suggest that Gal-3 plays an important role in Aβ aggregation and possibly in the pathology of AD.

近年來，基因與疾病之關聯分析 (association analysis) 越來越受到研究學者重視，因為在複雜性疾病與易感性基因之探討中 傳統的連鎖方法 (linkage method) 已不適用，所以複雜性疾病與易感性基因的關聯分析也蓬勃發展起來。在本文中我們主要是在探討 關聯分析中以家庭為研究資料與以群體為研究資料之間的優缺點，進而取長補短提出結合兩種資料之新的關聯分析方法 來增加估計與檢定之效力。我們同時考慮環境因素，探討基因因素與環境因素之交互作用。 本研究共分為三部份。第一部份探討如何整合病例-父母/病例-同胞 (case-parent/case-sibling) 與病例-對照 (case-control) 研究。我們提出一個加權最小平方 (Weighted Least Squares) 的方法將病例-父母/病例-同胞與病例-對照分析之估計式加以結合，以增進統計檢定之效力。 第二部分旨在探討基因-環境之交互作用。我們提出一個二階段研究設計法。在第一階段研究中，先收集病例資料; 在第二階段研究中，再收集其相對應之控制組資料。我們提出一個迴歸估計式以結合第一階段之單純病例分析(case-only analysis) 與第二階段之病例-對照分析。此建議之估計式即使在基因因子與環境因子 獨立之條件 (此條件為單純病例分析所必需) 不成立的情形下，依然可得出正確之統計推論。 第三部份旨在探討群體分層 (population stratification) 存在 之情形下，基因-環境之交互作用。我們提出一個二階段研究設計，以病例資料為第一階段資料， 再從病例資料中隨機抽取一部份病例患者之父母資料為第二階段資料。我們提出一個迴歸估計式結合單純病例研分析與病例-父母分析之估計式。 此新估計式即可整合單純病例分析與病例-父母分析，同時在群體分層存在之情形下，仍可得出有效之統計推論。 / In recent years, there are increasing attention to association studies, because linkage method will not be suitable under complex disease and susceptible genes. In the thesis, we are probing into association of family study and population study. And we combine family study and population study for increased efficiency of association method. We also consider interesting studies about gene-environment interactions. The thesis contains three projects. The first project focuses on examining when and how the two sources of information offered by such studies, one from the case-parent/case-sibling analysis, and the other from the case-control analysis with data from affected subjects and unrelated controls, can be integrated to enhance statistical power. We propose a weighted least-squares approach to linearly and optimally combine separate estimators from the case-parent/case-sibling and the logistic regression analysis for the association parameters. In the second project, we focus on examining the situation of gene-environment interaction. We propose a two-stage design. In the first stage, we collect patient data, and we seek out control data with respect to cases in the second stage. We propose regression analysis estimation in order to combine the case-only analysis in the first stage and the case-control analysis in the second stage. This estimation earns the correct statistical inference when genes and environment factors are not independent. In the third project, we explore gene-environment interactions under population stratification. We propose a two-stage design. In the first stage, we collect patient data, and we randomly collect a partial data of patient's parent from the cases in the second stage. We propose regression analysis estimation in order to combine the case-only analysis and the case-parent analysis. This estimation can combine the case-only analysis and the case-parent analysis, and attains effective statistical inference under population stratification.