Market Reaction to Non-tradable Share Desterilization: An Explanation Based on Heterogeneous Beliefs

从2006年6月19日第一笔股改限售股解禁事件开始，股改限售股解禁已渐渐成为全社会关注的焦点。限售股解禁将给市场带来什么冲击？流通股股东将如何应对？本文试图从异质信念的角度来分析这些问题。 异质信念对股票收益影响的理论研究最早始于Miller（1977），他认为在异质信念和卖空限制的前提下，投资者对未来的不同预期将会影响股票价格的均衡，对未来持乐观态度的投资者将会买入和持有股票，悲观的投资者却因为卖空限制而不能参与市场交易，其结果是股票价格主要反应了乐观投资者的意见，造成了股票价格相对于其真实价格的高估。随着时间的推移，信息传递逐渐充分，投资者意见逐渐趋向于一致时，价格会趋向于真实价值，异质...Since the first non-tradable shares became tradable on June 19, 2006, the desterilization of non-tradable shares came to our sight gradually. Questions such as what impact the selling off will bring to the market and how the tradable share-holders should react are what this thesis tries to answer from the prospective of heterogeneous beliefs. Miller (1977) first studied the influence of heterogen...学位：经济学硕士院系专业：经济学院金融系_金融学(含保险学)学号：1562006115099

Synthesis and biodistribution of ~(18)F-labeled pyridyl pyridaben analogues

目的设计并合成一种氟-18标记的哒螨灵类似物:4-氯-2-叔丁基-5-[[6-[[4-[2-[2-[2-氟[18f]乙氧基]乙氧基]乙氧基]-1H-1,2,3-三唑-1-基]甲基]-2-吡啶基]甲氧基]-3(2H)-哒嗪酮([18f]fPTP-P3),并评价其用于心肌灌注显像的可能性。方法采用[18f]f-取代OTS前体的方法进行标记,通过稳定性研究、脂水分配系数测定、生物分布实验等手段对标记物进行评价。结果 [18f]fPTP-P3的总制备时间为70~90 MIn,校正后的放化产率为36±5.6%,放化纯>98%。[18f]fPTP-P3为脂溶性化合物,在水溶液中可稳定放置3 H以上。生物分布实验结果显示,[18f]fPTP-P3在小鼠心肌具有一定的初始摄取,且肝部清除较快,但其心肌滞留较差。结论 [18f]fPTP-P3不具有用于心肌显像的潜力。Objective A fluorine-18 labeled pyridazinone derivative: 4-chloro-2-tert-butyl-5-[[6-[[4-[2-[2-[2-[18F]fluroethoxy] ethoxy]ethoxy]-1H-1,2,3-triazol-1-yl]methyl]-2-pyridinyl]methoxy]-3(2H)-pyridazinone([18F]FPTP-P3) was designed and prepared,and its potential as a myocardial perfusion imaging agent was evaluated.Methods [18F]FPTP-P3 was prepared by substituting tosyl of precursor with 18 F.The tracer was evaluated by stability study,octanol/water partition coefficient and biodistribution study.Results The total radio-synthesis time was 70-90 min,typical decay-corrected radiochemical yield was 36 ± 5.6%,and the radiochemical purity(RCP) was >98% after purification.It is a lipophilic compound,and stable in water for 3 h.The results of biodistribution study in mice showed that [18F]FPTP-P3 had certain initial heart uptake and the clearance of liver was very fast as well.However the retention of heart uptake was not ideal.Conclusion [18F]FPTP-P3 is not suitable for heart imaging in vivo.国家自然科学基金(20871020;81271613;21271030); 北京市自然科学基金(2092018)资助项目~

臺灣科技從業人員線上學習準備度之初探

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An Algorithm for Gene-Gene Interaction via Deviance of Independence

全基因組關聯研究 (genome-wide association studies, GWAS)為基因流行病學(genetic epidemiology)中典型的研究設計，用以偵測與疾病相關的基因分子。其基因資料，多半使用微陣列晶片技術偵測的單一核苷酸多型性（single nucleotide polymorphisms, SNPs）的實驗結果作為資料來源。分析的部分，則利用統計方法比較SNPs中各基因型(genotype) 裡疾病與對照組樣本數分布差異，找出可能與疾病相關的SNPs。以往GWAS多半針對單一SNP與疾病的相關性，但複雜疾病(complex diseases) 通常導因為基因之間或基因與環境因子之間存在的交互作用。現有偵測SNPs之間交互作用的方法，多屬於窮舉搜尋法(exhaustive search)，如多因子降維法(Multifactor Dimensionality Reduction, MDR)，針對每一種可能的組合做運算，因此只適合探討少量SNP中的交互作用。本研究目的是建立一個篩選的機制，從大量SNPs資料中篩出一個候選SNPs集合 (candidate SNP set)，而此集合的SNPs有較高的機會存在對疾病有影響的交互作用。 方法的建構是根據機率的獨立性，利用兩個單一SNP在樣本中分布的頻率，計算假設兩者之間獨立時，兩SNPs同時出現在樣本的頻率期望值。而另一方面算出兩SNPs同時出現在樣本的真實頻率值。根據真實值與期望值的偏差(deviance)，針對每一個成對的SNP組合，建立出一個獨立性偏差值(Deviance of Independence, DOI)，以部分反映此組合的交互作用程度。DOI演算法主要是針對GWAS裡，不具邊際效應(marginal effect)的SNP資料而設計。用來篩出那些在一階檢定不顯著，但經組合之後，能對樣本的疾病狀態有更大的鑑別力的SNPs。藉由模擬資料(simulation data)與真實資料 (real data application)的測試，我們發現利用DOI演算法進行篩選後，可以從中找出顯著的SNPs組合。此研究利用模擬資料，發現DOI演算法有良好與穩定的預測效果。另外在真實資料的實作上，在DOI篩選過後的SNPs集合中，可能可以找出有意義的SNPs組合。因此，DOI演算法為有效篩選基因交互作用的方法。Genome-wide association studies (GWAS) are commonly used study designs in genetic epidemiology to identify the genetic factors associated with diseases. Most of GWAS adopted single-locus strategy to analyze the association between individual single nucleotide polymorphism (SNP) and diseases. However, complex diseases may cause by one single gene but the gene-gene or gene- environment interactions. Exhaustive search methods, such as multifactor dimensionality reduction (MDR), are popular for detecting gene-gene interactions. Such kinds of methods require enormous computations and therefore are only feasible for small number of SNPs. As a result, this study aims to construct a filtering criterion for a candidate SNP set from large number of SNPs based on the independency of SNPs, called the deviance of independent (DOI). We apply DOI in GWAS data to filter those SNPs without marginal effect individually but have better ability to discriminate between cases and controls when they pool together. We use simulation and real data to examine DOI performance. The simulation results show that SNPs with interactions are along with higher DOI values. In addition, the 2-way and 3-way gene-gene interactions in a real data are examined as well. And the results demonstrate that possible interactions can be identified after using DOI value as filter criteria. In sum, DOI algorithm is a powerful tool to filter a candidate gene set for further interaction analysis

Avian Sexing and the Detection of Newcastle Disease and Avian Influenza Viruses Using Oligonucleotide Microarrays

國內每年救傷收容或新進檢疫的野生鳥禽（如各縣市野鳥協會，南投集集特有生物中心，各公私立動物園等）數量龐大。 然而由於多數無法由外觀判定性別，使得後續的繁殖、保育及管理等工作窒礙難行。此外野生鳥禽攜帶人畜共同傳染病病原的機會相當高，且常為不發病的潛伏帶原者，故如何篩檢帶原疾病並確定病原的種類， 以採取對應措施而及時杜絕疾病的傳播，是疫病防治上亟待解決的問題。另外由於鳥類天生的易緊迫性，如何減少因採樣緊迫所帶來的損傷，也是本研究考量的重點之一。DNA微陣列(DNA microarray)，又稱為DNA晶片，依探針的長短可分為cDNA微陣列及寡核酸微陣列兩種，為近十年來發展的新興技術。藉由樣本核酸分子與探針之間專一性結合後所顯示的訊號，可在極小的晶片上迅速得到大量的基因分子訊息，其對遺傳基因的分析或是病原的偵測診斷，提供了一個快速方便的檢測途徑。此研究的目的是希望利用DNA微陣列可以同步檢測多重核酸分子的特性，更精準快速地鑑定各類鳥種的性別，以突破現行各種鑑定法的瓶頸。本研究同時針對兩項重要的人鳥共同傳染病-新城病(Newcastle disease, ND) 與家禽流行性感冒(Avian influenza, AI)，作同步檢測與病毒分型，以檢視鳥禽帶原狀況並及時防堵病原的入侵。研究方法如下：首先對各類鳥禽的性聯基因作定序，擷取基因庫中各型家禽流行性感冒與新城病病毒的核酸序列，再經由進一步的比對分析，分別設計高度專一性的引子與探針，接著各自開發單一的PCR檢測法，並建立陽性對照組；再逐一修正合併成多引子聚合酵素連鎖反應(Multiplex PCR)的模式，以增進多重核酸分子的檢測效能。將設計好的各個探針點漬在晶片不同的位置上，完成DNA微陣列的製作；再把待測樣本的核酸標的分子以多引子聚合酵素連鎖反應方式大量增殖後，與晶片上的探針作雜交反應。配合陽性對照反應的結果，進行雜交反應訊號的比對與解讀，由此判斷受檢個體的性別，或是作病毒的篩檢與分型。在我們的研究結果中發現羽毛的羽軸，特別是靠基部的前半部是一個很好的體基因DNA (genomic DNA)的來源，此意謂著羽毛檢體並不需要用拔毛的方式獲得，以剪取的方式取得羽軸前半部即可，此法可大大降低受檢鳥體所受的傷害與緊迫。在鳥類性別檢測方面，我們併用兩個CHD1基因的插入子(intron)作多引子聚合酵素連鎖反應，透過寡核酸微陣列上所設計的9個探針的同步作用，已可檢測至少80種涵蓋26科(family)以上不同的鳥類。在病毒檢測方面，我們將ND病毒的融合蛋白質(fusion protein)基因， AI病毒的基質蛋白質(matrix protein)基因以及AI病毒的血球凝集素(haemagglutinin) 基因，作多引子聚合酵素連鎖反應的同步增殖，再利用寡核酸微陣列上所設計的12個探針之聯合作用，已可成功同步檢測ND病毒與AI病毒並作病毒的分型。寡核酸微陣列檢測系統在鳥類性別與人畜共同傳染病的開發與應用，將提供另一快速檢測的途徑，有助於野生鳥類的保育繁殖與疾病防疫體制的建立。There are numbers of wild birds rescued or quarantined in Taiwan each year. Most of them are endangered species. Their rarity poses great responsibility of us on breeding. Information of an individual bird’s sex, thus, is critical to the breeding strategies and conservation programs. Wild birds are important carriers for many pathogens, e.g. Newcastle disease virus, avian influenza virus and others. Early detection of these pathogens from carrier birds is important for the disease prevention from spreading to susceptible herds. DNA microarray, also called DNA chip, is a newly developed technique this decade. It is divided into cDNA microarray and oligonucleotide microarray based on the size of probes. Lots of molecular information is obtained at the same time through hybridization between target DNA and probes on the microarray. It provides a rapid approach to the gene analysis and pathogen detection. The purpose of this study is to develop an oligonucleotide microarray system which can precisely determine the gender of diversified avian species. Simultaneous detection and differentiation of the most two important zoonotic viruses, Newcastle disease virus and avian influenza virus, is also the main objective of this research. Most birds are vulnerable to stress. How to decrease injuries while handling, therefore, is a major consideration. Sex-related gene markers of various avian species were sequenced. The sequencing nucleotides, including the sequences retrieved from the GenBank, were aligned and analyzed, and specific primers and probes were designed. Each respective PCR method was developed, and then gradually integrated into multiplex PCR. The probes were spotted to specific positions on the microarray polymer substrate. Hybridization between target DNA and probes was performed on the array surface. The information of the gender and the carried pathogens were then obtained according to the hybridization pattern on the microarrays. We found that a cut feather including the scapus, instead of a plucked feather, is a good source of genomic DNA for bird sexing. It means this cutting method could substantially decrease injury to the examined birds. The nine designed probes on microarrays combined with two-CHD1 intron approach have successfully identified the sex of 80 avian species covering 26 families. Moreover, the 12 designed probes on microarrays targeting fusion protein gene of NDV, matrix protein gene of AIV and haemagglutinin gene of AIV also have successfully detected and differentiated different types of viruses simultaneously. Oligonucleotide microarrays, therefore, may provide potential for rapid sexing and zoonosis detection. It would be conducive to the conservation and zoonosis prevention of wild birds.Certificate………………………………………………………………………... Icknowledgments……………………………………………………………...... IIbstract in Chinese……………………………………………………………… IIIbstract…………………………………………………………………………... Vntroduction……………………………………………………………………… VIIontents………………………………………………………………………...... IXist of Illustrations………………………………………………………………. XIIIist of Tables……………………………………………………………………... XIX. Literature Reviews…………………………………………………………… 11.1 DNA microarrays………………………………………………………… 11.2 Avian sexing……………………………………………………………….. 41.3 Newcastle disease and avian influenza………………………………….. 81.3.1 The characteristics of both Newcastle disease and avian influenza..... 81.3.2 Newcastle disease……………………………………………………….. 101.3.3 Avian influenza………………………………………………………….. 13. Cut feather containing rachis as a sampling way for avian sexing………... 182.1 Abstract…………………………………………………………………… 182.2 Introduction………………………………………………………………. 182.3 Materials and methods…………………………………………………… 192.4 Results…………………………………………………………………….. 212.5 Discussion…………………………………………………………………. 222.6 Conclusion………………………………………………………………… 23. Sexing a wider range of avian species based on two CHD1 introns with a unified reaction condition……………………………………………………. 63.1 Abstract…………………………………………………………………… 263.2 Introduction………………………………………………………………. 263.3 Material and methods……………………………………………………. 273.4 Results…………………………………………………………………….. 283.5 Discussion…………………………………………………………………. 303.6 Conclusion………………………………………………………………… 31. Avian sexing using multiplex PCR- a more precise and simplified method 414.1 Abstract…………………………………………………………………… 414.2 Introduction………………………………………………………………. 414.3 Materials and methods…………………………………………………… 434.4 Results…………………………………………………………………….. 444.5 Discussion…………………………………………………………………. 45. Sex identification of owls (family Strigidae) and other avian families using oligonucleotide microarrays…………………………………………... 85.1 Abstract…………………………………………………………………… 485.2 Introduction……………………………………………………………… 485.3 Material and methods……………………………………………………. 505.4 Results…………………………………………………………………….. 535.5 Discussion…………………………………………………………………. 55. Simultaneous detection and differentiation of Newcastle disease and avian influenza viruses using oligonucleotide microarrays………………... 66.1 Abstract…………………………………………………………………… 666.2 Introduction………………………………………………………………. 676.3 Materials and methods…………………………………………………… 706.3.1 Viruses…………………………………………………………………… 716.3.2 Primers and probes…………………………………………………….. 716.3.3 RNA extraction and multiplex RT-PCR………………………………. 726.3.4 Oligonucleotide microarray preparation and hybridization reaction. 736.4 Results…………………………………………………………………….. 746.4.1 Multiplex RT-PCR……………………………………………………… 746.4.2 Oligonucleotide microarray assays……………………………………. 756.5 Discussion…………………………………………………………………. 756.6 Conclusion………………………………………………………………… 78. General discussion……………………………………………………………. 86. References……………………………………………………………………... 92. Appendix………………………………………………………………………. 1079.1 Published or accepted papers……………………………………………. 1079.2 Symposium papers………………………………………………………... 10