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    [[alternative]]Genetic Alterations of Mismatch Repair Genes in Lung Tumorigenesis in Taiwan

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    [[abstract]]貳、英文摘要 Lung cancer is the leading cause of cancer deaths in Taiwan. Genetically determined variation in DNA repair capacity is thought to contribute to susceptibility to tobacco-related cancers, such as lung cancer. In addition, defects in mismatch repair (MMR) genes have been implied in several types of sporadic and hereditary cancers in terms of inducing microsatellite instability (MI) of tumor cells. We have previously found that MI occurs in 41% of non-small cell lung cancer patients (NSCLC). However, there was only little report discussing the MMR gene alteration in lung cancer. In order to elucidate the role of MMR in human lung carcinogenesis in Taiwan, we examined the alteration of two DNA mismatch repair genes, hMLH1 and hMSH2, in primary lung tumor tissues from NSCLC patients. We investigated the expression levels of hMLH1 and hMSH2 proteins in 169 and 77 NSCLC tumors , respectively, by the immunohistochemical analysis. Ninety-six (56.8%) patients had the alteration of hMLH1 protein expression; thirteen patients (17.1%) had the alteration of hMSH2 protein expression. In addtion, we found that the alteration of protein expression correlated with the aberrant mRNA expression by RT-PCR assay for both hMLH1 and hMSH2 (P=0.001). The alteration frequencies of mRNA expression were 55.8% and 15.6% for hMLH1 gene and hMSH2 gene, respectively. To further examine the role of promoter hypermethylation in the identified alteration of protein expression, we also examine the association between hMLH1 promoter hypermathylation and hMLH1 protein expression. Forty-five (73.8%) patients containing hMLH1 promoter hypermethylation showed the alteration of protein expression (P = 0.001). The results suggested that mismatch repair plays a significant role in NSCLC tumorigenesis in Taiwan and that hMLH1 promoter hypermethylation is closely relative to the altered expression of mRNA and protein in the hMLH1 mismatch repair gene. Furthermore, we conducted a loss of heterozygosity (LOH) analysis at 3p21 microsatellite polymorphic marker D3S1768 for the deletion of hMLH1 region in a series of 39 NSCLC patients. The high percentage of LOH (56.4%) was observed at the D3S1768. The result suggested that loss of chromosome 3p21 may be also a critical event in the pathogenesis of lung cancer in Taiwan. To investigate the association of hMLH1 alteration with MI, we also studied the correlation between MI and expression of hMLH1 mismatch repair protein in 73 patients. Twenty-seven of 37 MI-positive patients (73.0%) did not express hMLH1 protein. The data showed that MI was associated with altered hMLH1 expression (P=0.025). In addition, there was a tendency of association between LOH at D3S1768 (3p21) region and MI (P=0.092). The correlation suggests the alteration of the hMLH1 gene/ protein may be associated with microsatellite instability (MI) because of the failure to correct replication slippage errors. In conclusion, our data suggest that alteration of hMLH1 gene and/or protein involved in lung tumorigenesis in Taiwan. The major alteration mechanism may be the promoter methylation of hMLH1 gene, and therefore inactivating its mRNA and protein expression. Moreover, LOH of the hMLH1 gene can also play an important role in alteration of hMLH1 gene. As regards hMSH2 gene, the data indicated that hMSH2 does not play a major etiological role in lung tumorigenesis in Taiwan. Validating the promoter hypermethyaltion and LOH in other mismatch rapair genes are worthy of further investigation in lung cancer tumorigenesis in Taiwan.

    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

    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

    Author Under Sail The Imagination of Jack London, 1893-1902

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    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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