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    Data Analysis and Determination of Sample Size for the Dye-Swap Two-Color Spotted Microarray Experiments

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    隨著生物技術的快速發展,雙色微陣列晶片實驗的應用日漸廣泛。然而在微陣列晶片實驗過程中,常包含釵h系統誤差,造成實驗最後所得到的數據往往不夠準確,因此如何將資料中所包含的系統誤差扣除,找出真正表現有顯著差異的基因是釵h學者爭相討論的問題。 本研究中主要針對dye-swap實驗下的雙色微陣列晶片實驗資料,利用對數比模型來作資料分析,對數比模型與一般微陣列晶片資料分析所採用的ANOVA模型不同之處在於:一般ANOVA模型是以每個光強度的對數值當反應變數,而我們使用的對數比模型則以成對的紅、綠光強度比值的對數值當反應變數,其中又可分為一階段對數比模型及兩階段對數比模型。一階段對數比模型是假設所有基因的反應變數為齊質變方,但由於在微陣列實驗中,大多數的基因是表現無顯著差異,因此可能會造成表現有顯著差異的基因變方被低估。而兩階段對數比模型顧名思義即是將模型分為兩個部分來作探討。模型的第一階段主要在進行正規化的動作,而在模型的第二階段又根據假設的不同分為gene-by-gene模型以及混合機率分佈模型。gene-by-gene模型是假設各基因間非齊質變方,所以一個基因就有一個模型。混合機率分佈模型則是將基因表現分成表現有顯著差異及沒有顯著差異兩個族群來作討論。至於在判定顯著基因方面,一階段對數比模型採用一般的學生氏t檢定,gene-by-gene模型則利用Efron et al.(2001)提出的Sg統計量,而混合機率分佈模型則利用事後機率的勝算判定基因表現是否有顯著差異。 本研究最後也透過一階段對數比模型和gene-by-gene模型來討論決定重複數的問題。由於一階段對數比模型是在齊質變方的假設下,因此估計出來的變方可能過小,使得實驗所需的重複數被低估。而gene-by-gene模型中,N個基因就有N個變方,我們建議利用N個變方的第90百分位數作為決定重複數的依據。Microarray technology is a powerful tool to detect the expression level of many thousands of genes. However there are many sources of systematic variation which may bias the estimation of the gene expression. Hence how to remove the systematic variation and estimate the gene expression correctly are important topics in the micr- oarray experiment. In this study, we focus on the dye-swap two-color DNA spotted microarray experiments. We try to analyze the data collected from this kind of microarray experiments by some log-ratio models, which can be classified as one-stage log-ratio models and two-stage log-ratio models. In one-stage log- ratio models, we assume the variances of the gene expression for different genes are homogenous. However most genes in microarray experiments are not significantly expressed, hence the estimate of this unique variance may be actually smaller than the true values for the rest significant genes. Consider the two-stage log-ratio models, the first part of the two-stage log-ratio models can be regarded as a global normalization model and the second part is a gene-specific model. Moreover the gene-specific model can be regarded as gene-by-gene models or mixture probability density function models under different assumptions. The variances of the gene expression are assumed to be different in the gene-bye-gene models, leading to that every gene has it own model. Mixture probability density function models regard genes in microarray experiments as significantly expressed genes and non-significantly expressed genes, each population has its own probability density function. The Student’s t statistic is used in one stage log-ratio models to identify differentially expressed genes. Similarly, Sg statistic proposed by Efron et al. (2001) is used in two-stage gene-by-gene models. In mixture probability density function models, differentially expressed genes are determined by the posterior odds which is a kind of Bayesian approach. Finally, we consider the sample size based on the one-stage log-ratio models and the gene-by-gene models, respectively.目 錄 第一章 前言 …………………………………………………1 1.1 雙色微陣列晶片試驗之簡介……………………………… 1 1.2 研究動機與目的…………………………………………… 2 1.3 文獻探討…………………………………………………… 3 第二章 正規化及鑑別有顯著差異的基因………………… 4 2.1 正規化方法 ………………………………………………… 4 2.2 判定顯著基因…………………………………………………9 2.3 對數比模型………………………………………………… 11 2.4 實例應用…………………………………………………… 19 第三章 重複數之研究 ………………………………………44 3.1 多重比較…………………………………………………… 44 3.2 重複數研究………………………………………………… 46 3.3 結果與討論………………………………………………… 48 第四章 結論與未來研究……………………………………58 4.1 總結………………………………………………………… 58 4.2 未來研究及討論…………………………………………… 59 參考文獻 ……………………………………………………61 附錄A 對數比模型之S-plus程式…………………………63 附錄B 重複數之S-plus程式………………………………6

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Functional divergence and intron variability during evolution of angiosperm TERMINAL FLOWER1 (TFL1) genes

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    The protein encoded by the TERMINAL FLOWER1 (TFL1) gene maintains indeterminacy in inflorescence meristem to repress flowering, and has undergone multiple duplications. However, basal angiosperms have one copy of a TFL1-like gene, which clusters with eudicot TFL1/CEN paralogs. Functional conservation has been reported in the paralogs CENTRORADIALIS (CEN) in eudicots, and ROOTS CURL IN NPA (RCNs) genes in monocots. In this study, long-term functional conservation and selective constraints were found between angiosperms, while the relaxation of selective constraints led to subfunctionalisation between paralogs. Long intron lengths of magnoliid TFL1-like gene contain more conserved motifs that potentially regulate TFL1/CEN/RCNs expression. These might be relevant to the functional flexibility of the non-duplicate TFL1-like gene in the basal angiosperms in comparison with the short, lower frequency intron lengths in eudicot and monocot TFL1/CEN/RCNs paralogs. The functionally conserved duplicates of eudicots and monocots evolved according to the duplication-degeneration-complementation model, avoiding redundancy by relaxation of selective constraints on exon 1 and exon 4. These data suggest that strong purifying selection has maintained the relevant functions of TFL1/CEN/RCNs paralogs on flowering regulation throughout the evolution of angiosperms, and the shorter introns with radical amino acid changes are important for the retention of paralogous duplicates

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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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