1,720,991 research outputs found
Developing exo- versus endo-Labeling Probes for β-Glucosidase Towards the Application in Proteomics
No full text在生物體內，醣類衍生物被視為訊息攜帶分子，涉及免疫反應、病毒感染，以及細胞間的辨識與訊息傳遞等生物功能，其重要性使得醣質生物學（glycobiology）成為生命科學的新焦點。而醣苷水解酶在控制生物體內醣類的代謝、生成，以及細胞表面分子辨識上扮演了重要角色，若活性失調可能引起多種疾病。因此，這類酵素的研究將有助於臨床上疾病診斷與治療、藥物開發及病理瞭解等。在本論文中，是以商業上可購得來自杏仁的β-葡萄糖水解酶（β-glucosidase）為研究對象。並利用ABPP（activity-based protein profiling）策略發展其活性標示探針，以期能應用於蛋白質體學（proteomics）的研究上。我們成功發展了對β-葡萄糖水解酶具有標示潛力的光親合性（photoaffinity）活性標示探針B-1（為酵素表面標示的探針），以及以酵素催化機制為基礎的（mechanism-based）活性標示探針C-1（為酵素活性中心內標示的探針）。其中，探針B-1的設計包括了S-linked β-D-葡萄糖衍生物、光反應基團，以及生物素標籤。這三重功能性探針的設計是希望探針在與目標蛋白質專一辨識後，經由照光反應可以在活性中心附近形成共價鍵結，再由生物素的標籤輸出訊號。在探針B-1標示蛋白質的相關實驗中，已證實其能與目標酵素活性中心親合性結合，並以共價鍵連結。另外，探針C-1的設計包括了epoxyalkyl glucosides衍生物和疊氮（azido）基團。其設計是希望藉由酵素催化過程與探針上反應基團epoxide形成共價鍵結，再利用疊氮基團進行click反應連接標籤。而在標示蛋白質的相關實驗中，則發現缺乏epoxide的對照物C-1a標示效果較探針C-1佳，但目前仍未知其與酵素形成共價鍵的機制。此外，這些探針進行蛋白質標示的結果顯示配基為S-linked的探針B-1專一性較不高，而具有天然O-linked配基的探針C-1對β-葡萄糖水解酶具有專一性。最後，這些探針組裝式的合成提供了未來其結構改良的簡便性，可再經由配基或反應基團的置換等，來提升探針的專一性標示。In organisms, saccharide derivatives are deemed as information carriers, involving biological functions, such as immune response, virus infection, cell-cell communication and signal transduction, etc.. Their biological importance makes glycobiology become a new focus of life sciences. Among them, glycosidases play important roles in controlling saccharide metabolism, anabolism and cell surface molecule recognization. Any imbalance in their activities may result in many kinds of diseases. So the study of this kind of enzymes will benefit to the clinical diagnosis/treatment, drug discovery and understanding pathology etc. In this thesis, the commercially available β-glucosidase from almonds is used as the research model. Various ABPs (activity-based probes) were developed to label the enzymes hoping to extend the strategy to study proteome. We have succeeded in developing photoaffinitity ABP B-1 (exo-labeling probes) and mechanism-based ABP C-1 (endo-labeling probes), which exhibit potential in labeling β-glucosidases. Probe B-1 consists of a S-linked β-D-glucose derivative, a photoreactive group, and a biotin tag. This trifunctional probe is designed to form the covalent bond by photoreacting group near the active site once the probe and the targeted protein were bound together specifically and the biotin tag could be regarded as output for facile purification. In the protein labeling experiment employing the probe B-1, it showed that the probe can recognize the active site of the targeted enzyme specifically via a covalent bond. The probe C-1 is composed of a epoxyalkyl glucoside derivative and an azido group. A covalent bond between the enzyme and epoxide reactive group forms first, and then an azido group could react with the tag by click reaction afterwards. The protein labeling experiment using control C-1a, which has no epoxide, displayed good labeling effect, despite that the labeling mechanism is not clear. Moreover, probe B-1, which has S-linked ligand, cannot specifically label β-glucosidases, whereas probe C-1, which has native O-linked ligand, can specifically label β-glucosidases. To summarize, the study has laid the foundation for the development of ABPP (activity-based protein profiling) probes. Moreover, the modules nature of the probe designs offer molecular simplicity and concision. The specificity can be improved either by changing the ligand or reactive groups.目錄……………………………………………………………i
圖目錄………………………………………………………………iv
表目錄………………………………………………………………vii
簡稱用語對照表………………………………………………………viii
中文摘要……………………………………………………………xii
英文摘要………………………………………………………………………xiii
緒論…………………………………………………………………1
第一章 蛋白質體學之簡介
1.1 蛋白質體學之發展歷程…………………………………………………………6
1.1.1 蛋白質體學之定義與發展……………………………………6
1.1.2 傳統蛋白質化學與蛋白質體學研究之比較……………………7
1.2 基因體與蛋白質體之比較…………………………………………7
1.3 蛋白質體學之研究方法…………………………………………9
1.3.1 二維凝膠電泳法與質譜儀………………………………………10
1.3.2 化學蛋白質體學之ABPP方法………………………………11
第二章 醣苷水解酶之簡介
2.1 醣質生物學之簡介………………………………………………18
2.1.1 醣質生物學之發展歷程…………………………………………18
2.1.2 生物系統中醣類之功能…………………………………………19
2.1.3 醣類之結構特點…………………………………………………19
2.2 醣苷水解酶之重要……………………………………………………20
2.3 醣苷水解酶之作用機制……………………………………………22
2.3.1 醣苷水解酶之分類………………………………………………22
2.3.2 醣苷水解酶之催化機制………………………………………22
2.4 醣苷水解酶之抑制劑…………………………………………25
2.4.1 可逆抑制劑……………………………………………………25
2.4.2 不可逆抑制劑…………………………………………………27
2.5 醣苷水解酶之活性標示探針………………………………………33
2.6 目標酵素β-葡萄糖水解酶之簡介………………………………38
第三章 針對β-葡萄糖水解酶發展親合性活性標示探針
3.1 金奈米粒子之簡介…………………………………………………39
3.1.1 金奈米粒子之特性………………………………………………39
3.1.2 金奈米粒子之合成……………………………………………42
3.1.3 金奈米粒子應用於生物探針之簡介……………………44
3.2 親合性活性標示探針之設計與合成…………………………………………47
3.2.1 Dalibor Sames所發展具epoxide反應基團之親合性探針……47
3.2.2 親合性活性標示探針之設計………………………………….49
3.2.3 親合性活性標示探針之合成…………………………………51
3.3 結論……………………………………………………………62
第四章 針對β-葡萄糖水解酶發展光親合性活性標示探針
4-1 光親合性標示之簡介與應用………………………………………63
4.2 光親合性活性標示探針之設計與合成…………………………69
4.2.1 光親合性活性標示探針之設計…………………………………69
4.2.2 光親合性活性標示探針之合成………………………………71
4.3 結果與討論…………………………………………………………80
4.3.1 光親合性探針標示蛋白質之實驗流程…………………………80
4.3.2 光親合性探針標示蛋白質之結果分析………………………83
4.4 結論…………………………………………………89
第五章 針對β-葡萄糖水解酶發展以催化機制為基礎的活性標示探針
5.1 引入click化學的ABPP方法之簡介與應用………………………90
5.2 以酵素催化機制為基礎的活性標示探針之設計與合成…………94
5.2.1 以酵素催化機制為基礎的活性標示探針之設計………………94
5.2.2 以酵素催化機制為基礎的活性標示探針之合成………………97
5.3 結果與討論…………………………………………103
5.3.1 以酵素催化機制為基礎的探針標示蛋白質之實驗流程……103
5.3.2 以酵素催化機制為基礎的探針標示蛋白質之結果分析……105
5.4 結論………………………………………………………………121
第六章 總結…………………………………………………………122
實驗部分
壹、一般敘述……………………………………………123
貳、實驗步驟及光譜數據………………………………………125
參、生物活性測試方法……………………………………………165
參考文獻…………………………………………………174
附錄…………………………………………………………………19
A Study of Determinants of Successful Selling in the Internet Second-Hand Market
No full text網路購物是現代人經常使用的購物方式，透過網際網路，可使交易快速且便利之進行。然而，網路虛擬市場卻較傳統實體市場有著更高之不確定性風險，尤其在網路二手市場裡存在著更嚴重的資訊不對稱問題。本研究之主要目的即在於了解資訊不對稱對於網路二手市場交易結果之影響，同時參考過去學者之研究，挑選出可能影響網路二手市場消費者購買意願之因素(包括產品訊號、賣方信任和網路口碑)，透過實證分析方式，探討這些因素對於網路二手市場交易結果之影響。本研究所得之主要結果如下：
1.商品之絕對價格、相對價格與品牌評價愈高者，其交易成功之機率愈低，顯示網路二手市場可能因資訊不對稱而存在逆選擇之情形。
2.賣方有提供實物照片之商品，其交易成功之機率愈高，顯示產品訊號會影響網路二手市場之交易結果。
3.賣方發表文章數愈多之商品，其交易成功之機率愈高，顯示賣方信任會影響網路二手市場之交易結果。
4.推薦人數愈多之商品，其交易成功之機率愈高，顯示正面之網路口碑會影響網路二手市場之交易結果。Internet shopping is the shopping method modern people often use. The Internet can make the transaction fast and convenient. However, there is higher uncertain risk in the Internet virtual market than the traditional material market. Especially, the problem of information asymmetry is more serious in the Internet second-hand market. The major purpose of this study is to understand the influence that information asymmetry has on the trading results of the Internet second-hand market. Moreover, referring to research papers of past scholars, this study chooses some factors that may affect the buying wills of consumers in the Internet second-hand market, including signals of the product, seller trust and word-of-mouth of Internet, and confers the influence these factors have on the trading results of the Internet second-hand market through the empirical analysis.
The main findings of this study are as follows：
1.The higher the absolute price, the relative price or the appraisal of brand of the commodity is, the higher the probability of trading successfully is. It shows that there is adverse selection in the Internet second-hand market because of information asymmetry.
2.The commodity whose seller provides the actual photo has a higher probability of trading successfully. It shows that signals of the product may affect the trading results of the Internet second-hand market.
3.The more the seller issued articles, the higher the probability of trading successfully is. It shows that seller trust may affect the trading results of the Internet second-hand market.
4.The more recommendation population of the commodity is, the higher the probability of trading successfully is. It shows that the positive word-of-mouth of Internet may affect the trading results of the Internet second-hand market.第一章 緒論……………………………………………………… 1
第一節 研究背景與動機………………………………………… 1
第二節 研究目的………………………………………………… 3
第三節 章節架構………………………………………………… 4
第二章 文獻探討………………………………………………… 5
第一節 電子商務………………………………………………… 5
第二節 資訊不對稱………………………………………………11
第三節 訊號理論…………………………………………………16
第四節 信任………………………………………………………19
第五節 口碑………………………………………………………27
第三章 研究方法…………………………………………………32
第一節 研究架構…………………………………………………32
第二節 研究假設…………………………………………………33
第三節 研究範圍與對象…………………………………………33
第四節 研究變數…………………………………………………35
第五節 分析方法…………………………………………………37
第四章 樣本分析與迴歸結果……………………………………38
第一節 敘述統計分析……………………………………………38
第二節 迴歸分析…………………………………………………45
第五章 結論與建議………………………………………………49
第一節 研究結論…………………………………………………49
第二節 實務建議…………………………………………………52
第三節 研究限制…………………………………………………53
第四節 未來研究建議……………………………………………53
參考文獻………………………………………………………………54
附錄……………………………………………………………………5
Distributed Classification of Asynchronous Partial Model for Non-regular Drifting Data
No full text大數據資料強調大量、快速、多元、價值、及精確五種特性。涵蓋 多類型的資料，包括科學工程分析，社群網路，傳感器，物聯網，及 多媒體應用等。對於在大數據中，如何有效率地處理資料，進而轉為 結構性的資訊，其資訊探勘技術需求日趨迫切且更具挑戰。分散式分 類系統在整合分散式模型與資料扮演關鍵性的角色，分散式系統主要 是利用統計分析及協同整合子資料庫之模型，讓多個區域性裝置可以 同時蒐集資料。隨著大數據應用、無線與行動技術的普及，由分散式 裝置產生的各式不同特性之資料量逐漸增加。分散式分類模型面臨下 列數個巨量資料下衍生的難題：1) 非同步局部資料分散式分類, 地區性 裝置受限於有限資源如電力、資料儲存空間，及區域性或其他規劃等 因素，收集不完整屬性且僅有局部之資料。傳統收集完整資料，或是 利用抽樣統計等相關技術整合的方法，將不再適用非同步之不完整資 料的分散環境中。2) 就資料本身而言，快速變化的資料分佈，其變化 模式與改變趨勢亦隨著外在環境有所變動，其多元的變化亦增加傳統 分析及判斷資料是否改變之複雜度。若只使用單一固定長度之時間快 門觀察資料，將會大幅降低預測模式反應資訊變化之效能。3) 為了更 進一步擴充分散式分類模型的使用規模，利用模型轉換技術，將傳統 普及之高效率非規則式模型，轉化為可傳輸之規則式模型，因此，如 何將非規則式模型轉化為適當規則式模型，將成為決定分類模型效能 的關鍵。 本論文試著解決以上的問題，我們首先將目光著眼於分散式分類模 型系統，並設計一套整合非同步局部資料的分散模型之方法，使得整 體分散式分類系統的區域模型效能可以被妥善運用；由於分散式分類 系統允許區域裝置收集非固定量之區域資料，當收集資料以產生資料 模組時，因資料多樣性及變動多樣化等特性，單一時間窗所造成的錯 誤率也隨之上升而大幅降低系統效能，我們進而提出連續性叢集方法， 讓系統根據時間與資料分佈將資料適當切割以產生符合資料分佈之模 組。最後，本論文提出兩種模型轉換方法，使傳統無法傳至伺服器整 合之非規則式模型轉至規則式模型，以擴展分散式分類模型可使用之 規模並提升整體效能。不論是在理論分析或者實驗測試上，本論文所 提出之分散式分類模型皆較傳統分散式分類有更卓越的效能提升與更廣泛之應用。Big Data emphasizes on 5Vs (Volume, Velocity, Variety, Value and Veracity) relevant to variety of data (scientific and engineering, social network, sensor/IoT/IoE, and multimedia-audio, video, image, etc) that contribute to the Big Data challenges. This phenomenon introduces the urgent requirement for efficiently managing data to structured information. One predominate approach is distributed classification ensemble, which improve prediction efficiency by using ensemble of distributed model or integrated by combining distributed information via statistics, to allow multiple devices collect data concurrently. With the popularity of Big Data applications, wireless and mobile technology, the amount of data in various characteristics generated by distributed devices has been tremendously increasing. As a result, distributed classification in Big Data has new challenges. There are three main challenges in distributed big data systems: 1) the distributed classification models are asynchronous and incomplete from distributed devices. Traditional distributed classification algorithms, which rely on horizontal sub-databases or vertical sub-databases, cannot be applied in this scenario. 2) Due to various characteristics of Big Data, simply separating data to equal size for constructing models takes away the significant performance benefit of classification models. In particular, non-regular recurring data are especially vulnerable to models derived from equally separated windows because noise data interfere most of the models in fixed-size buckets. 3) In our distributed environment, arbitrarily transforming popular lazy models to rules will increase the diversity of local models and reduce additional transmission bandwidth consumption. This dissertation tries to solve the above problems. First, this dissertation focuses on distributed streaming environment scenario, and proposes a rule-based distributed classification for asynchronous partial data (DIP). Our proposed method DIP selects models based on the amount of local databases and the quality of local models such that the performance gain can be fully utilized. DIP saves the communication bandwidth by transferring organized information, instead of individual instances. In addition, our distributed classification method DIP enables local devices collect various amount of local data. Due to data diversity and change diversification, the performance of classification models built from fixed-size windows or chunks declines. We investigate the data characteristic of non-regular data and introduce sequential clustering which adaptively forms sequential clusters of data based on data distributions and time to reduce noise data of inter-cluster interference and enhance classification prediction of derived models. Finally, this dissertation proposes two model transformation methods, which transforms data distributions to rules, to facilitate popular lazy classifiers in our distributed classifier. In both theory analysis and tested experiments, the proposed distributed classification framework can achieve a significant performance gain and bigger scope, as compared to the traditional distributed classification ensemble and existing dynamically changing methods
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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