一等獎

Coronavirus Disease 2019 (COVID-19) is a newly emerged infectious disease caused by the new severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV-2). In less than one year, the virus has spread around the entire world, killing millions of people and disrupting travel and business worldwide. During infection, the virus uses its Spike protein to dock onto the Ace2 protein on the surface of its human host cell. Spike is 1273 amino acids long and only a short fragment of Spike (319-541) is sufficient to bind Ace2. We hypothesized that the remaining protein sequences of Spike might have functions for viral replication beyond the binding of Ace2. We have performed Split-Ubiquitin protein-protein interaction screens to isolate human proteins by their ability to bind to Spike, and we have identified Annexin2A2 and Cytochrome b as novel human protein interaction partners of Spike. Annexin2A2 is involved in both endocytosis and exocytosis, and the protein interaction with Spike might help the virus to enter and exit its host cell. The presence of the mitochondrial Cytochrome b protein inside the cytosol promotes apoptosis, and the protein interaction with Spike could speed up sapoptosis of the infected human cell. The Nub cDNA libraries that we have generated also allowed us to screen for synthetic peptides that interact with Spike. We have isolated two synthetic peptides, FL1a and FL7a, derived from the non-coding parts of human mRNAs by their ability to interact with Spike. We found that both FL1a and FL7a interact with the C-terminal half of the Spike protein. We also found that FL7a is able to block the Spike-Spike self-interaction at the C-terminal half of the Spike protein and we think that this could block the reassembly of the Spike protein in the host cell during viral reassembly. We hope that those synthetic peptides could be used as drugs due to their ability to block protein-protein interactions of Spike with human host proteins that are essential for viral replication.

肺癌是目前全世界首要致死的癌症。雖然現有的標靶治療與免疫療法已經改善某些病患的情況，但有許多病患仍無有效治療方法。因此，我們急需探求新的藥物治療方法來改善肺癌治療的成效。 在此我們選擇一個新標靶藥物Palbociclib來進行研究，Palbociclib 是剛核准的乳癌藥物，主要是藉由抑制CDK4/6來延緩乳癌生長。我們發現Palbociclib能有效地抑制肺癌細胞株的生長和死亡。特別的是，Palbociclib不僅誘發肺癌細胞凋亡(apoptosis)，亦誘發肺癌細胞自噬死亡(Autophagy)。因為AMPK能同時影響細胞凋亡與自噬死亡，我們進一步研究AMPK在Palbociclib誘發癌細胞死亡中的角色，發現Palbociclib主要是藉由抑制去磷酸酶PP5的活性，來增加AMPK的磷酸化，進而活化AMPK，誘發肺癌細胞產生凋亡與自噬。這些藥效原非抑制CDK4/6會產生的作用，我們發現Palbociclib藉由調控PP5-AMPK路徑以誘發細胞死亡。希望這些研究結果能幫助肺癌的臨床研究，以造福病患。

本研究探討年際氣候震盪對全球平均海平面的影響，故將衛星測高儀數據剔除長期趨勢與季節波動後，與數個氣候指數進行互相關及同調性頻譜分析，其結果為：(i) 海平面與 ENSO，尤其是 Central-Pacific Types 在一年半以上的時間尺度，有高度相關，相關的原因可能與混合層溫度變化、陸地降雨海陸分布的變化有關。(ii) 海平面與 PDO、AMO 的相關性分別集中在 4 年以上與 2 年到 10 年，海水的熱含量變化可能是主因。AMO 相關性最高是在其比海平面早發生 8 個月的時間。 (iii) 雖然研究資料不包含北極海，但結果指出海平面與 AO 有弱相關，意味著北極海的年際溫鹽變化，對於全球海平面有遙相關的影響。(iv) 海平面與 AAO 似乎有弱相關，但是無法確定。最後本研究將上述五個指數以最小平方法擬合海平面年際變化，得到各指數的相對強度貢獻比例，有助於了解在未來全球暖化下的海平面變化。

Money drives the world and in times of crisis, money is more important than ever. Most political, economic and, as we have seen recently, health crises are accompanied by pressure on the economy. With such pressure, ordinary citizens are worried about their money, which is at risk either from inflation or from an uncertain economic outlook. In such times, some people resort to appreciating their money by investing. It is wise investments that can protect savings from inflation, or at least mitigate the effects of inflation. Investing in the stock market is among the most popular ways of investing. During the global coronavirus crisis, the number of small investors more than doubled (Galik and Brody [2022]), and in 2021, Covid (new) investors accounted for 15 % of investors in the U.S. market (Schwab [2021]). It is this phenomenon that inspired the author to write this paper. Investing in the stock market is one of the riskiest forms of investment, which means that there is a high probability of losing the originally invested capital. Some companies that allow retail investors to invest state that more than 90 % of their users lose their capital when investing in the stock market. On the other hand, investing in the stock market has one of the greatest potentials for profit. In the case of a long-term investment in index funds, for example, an average annual appreciation of between 8 % and 12 % can be expected (the average appreciation of the S&P 500, the most famous US index). However, it is necessary to wait several years for stable results. To see appreciation in a long-term portfolio, it is recommended to wait at least 12 years. This is because if a recession or a simple market correction comes, said portfolio can lose up to 50 % of its value in a year. But as history shows, markets do rise over the long term, and that is what long-term investors bet on, waiting for their capital to appreciate over time. But the market does not grow all the time. The market often changes price trends, and in some rare cases a long-term trend can reverse for up to several tens of months. This phenomenon, volatility, is attempted to be exploited by so-called speculators. A speculator is an investor who sells and buys in short periods of time and thus speculates on price movements. The speculator therefore needs a way to determine the likely behaviour of the price in the foreseeable future in order to make their trades profitable. The two main ways of analysing price behaviour are fundamental and technical analysis. And since fundamental analysis incorporates a large amount of diverse information into its predictions, this paper concentrates on working with technical analysis.

角膜塑型術的原理是於夜晚睡覺時，採用多弧的逆幾何設計來壓迫角膜，使角膜表皮細胞重新排列以達到矯正的效果。然而在夜晚配戴期間淚液分泌物會吸附於角膜塑型片表面，造成角膜擦傷、感染。本研究探討多醣類對角膜塑型片表面淚液分泌物之吸附的影響。從實驗結果中可以看到淚液分泌物會隨天數而堆積於鏡片上且表面粗糙度有大幅上升趨勢，在進行了市售主流系統產品之測試後發現其清潔效果並不顯著，而我們藉由蛋白質、脂質濃度分析、掃瞄式電子顯微鏡觀察及表面水接觸角觀察可以得出加入多醣類(AA/CRG各4.5mg/ml)的複方清潔可以最有效的提升清潔效果。未來我們期望可以將多糖類複方清潔液帶入安全性評估及成本分析並成功商品化。

本研究開發一個新型的CRISPR-Cas9技術剪輯粒線體DNA，提供粒線體基因所造成疾病的一個有潛能之治療方式。在本研究中，我們將嵌入粒線體標的訊號序列後的 Cas9 蛋白質和 sgRNA 分子送入粒線體內，將 CRISPR-Cas9系統套用於粒線體中，並達成剪輯粒線體基因之目的。我們將 Cas9 蛋白質和 sgRNA 分子鑲嵌於同一質體上，有效導入CRISPR-Cas9系統於粒線體內，並觀察到剪輯之標的基因ND4含量下降了 32%，達到粒線體基因編輯之目標。雖然前人曾用ZFN (Zinc-finger Nuclease)和TALEN (Transcription Activator-like Effector Nucleases)成功編輯粒線體基因，但由於製作過程繁瑣和經費昂貴等種種原因，並未被廣泛使用。我們開發的新型CRISPR-Cas9粒線體基因剪輯系統將可以提供一個相對簡易且價格低廉的粒線體基因剪輯平台。

甜菜黃素為植物內水溶性色素，以植物4,5-多巴雙加氧酶催化L-多巴形成甜菜醛胺酸，再與胺基化合物可得到甜菜素。甜菜素極佳的抗氧化性被認為可發展有效的抗癌保健。 目前甜菜素由植物萃取與植物酵素合成，近期研究發現某些微生物有可催化L-多巴轉換機制的4,5-多巴雙加氧酶，但資訊未完備。又偵測L-多巴可診斷初期帕金森氏症，此酵素的催化機制可檢測L-多巴。 本研究探索微生物源4,5-多巴雙加氧酶，經基因體探勘、基因選殖與蛋白表現後，將重組蛋白純化並探討結構與功能。目前已進行活性測試、得到蛋白最佳反應環境，並分析兩種蛋白質結構，比較兩種蛋白結構與活性之關聯性；以及進行酵素動力學實驗。亦已開始著手應用層面，成功設計並合成出雙加氧酶與酪胺酸酶之引子。 未來期待以結構資訊改良酵素；應用面用於測定醫療之L-DOPA，加入酪胺酸酶於細菌大量生產甜菜素。

臺灣已進入高齡社會，步態復健對於亞健康及慢性病族群極為重要，以帕金森氏症患者為例，他們常行走困難且容易跌倒。提升跨步品質的視覺提示是非常有效的協助方式，但臨床多仰賴治療師在地上貼膠帶或擺物件，調整不易且只受限於特定場所，因此居家自行照顧困難。先前已有研究開發出輕便可攜的裝置，能調整視覺提示，但每位使用者對不同提示模式的反應不一。本研究提出創新方法解決治療師手動調整的問題。以低成本周邊所建置的系統已能即時無線的變換不同提示模式、調控其參數，和自動計算各步態參數。其使用MG90s伺服機調整投射角度、霍爾式旋轉角度計裝在輪子上測量位移、Wi-Fi無線接收及操控參數。已經完成自動化探索使用者能力，並作最佳化的視覺提示設定。讓使用者不必出門，居家使用時，皆有最佳的視覺提示設定，得以更短的時程達到更好的復健效果。

色彩知覺是人類最重要的感官之一。由於形狀、亮度、空間頻率和色彩組成的不同，每個人對色彩的感知也有所差異。我們對此現象感到著迷，並決定進行一項研究，以識別和量化不同情況下的色彩誘導。 本研究選擇以環狀刺激作為主要圖像，以測量人類視覺色彩誘導。而本實驗主要利用紅色與綠色的誘導效果。實驗中，我們採用紅色及綠色基準做為目標環狀區域，並於其中添加可變性紅色目標，以測量受試者之視覺閾限。在色彩誘導的情況下，透過環狀刺激與測量所得之視覺閾限，我們可以識別並量化環狀刺激對色彩感知造成的影響。此外，我們也發現了環狀刺激中的單一環形如何影響人們對目標環狀區域的色彩感知。 我們利用實驗所得之結果，建立了一個預測並描述色彩錯覺與細胞反應相關性的模型，而此模型將會讓我們對人類視覺系統及神經間的側交互作用有更深一層的了解。

本研究初步分析颱風雷達回波圖發現，利奇馬、蘇力、柯羅莎、杜鵑4個雙眼牆的颱風，內眼牆有沿著外眼牆內側旋轉的現象，時間尺度約為3至14小時。接著比較颱風個案，選定杜鵑颱風作為主要觀察研究對象，以探討影響雙眼牆颱風內眼牆滾動週期的因素為研究目標，並以數值模式簡化問題。我做出兩種猜測，認為此一現象的成因，有可能是眼區的繞轉，或是內眼牆被眼區內的正渦度帶動旋轉。我先後設計了單、雙眼牆旋轉實驗，發現影響此二系統旋轉週期的主因不盡相同。其中，從雙眼牆實驗的結果可以發現，影響內眼牆滾動週期的參數，主要是眼區半徑以及眼區渦度，呼應了內眼牆受眼區內渦度帶動旋轉的猜測。最後，我在模擬杜鵑颱風的實驗中，做出相似的旋轉週期，證明內眼牆滾動的機制，主要以水平動力為主，也證明先前實驗的參數，即是影響旋轉週期的要素。