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    The Modulation Effects of Calmodulin on Voltage-gated sodium channels

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    電壓依賴型鈉離子通道(voltage-gated sodium channel, VGSCs)在引起細胞動作電位(action potential)及動作電位的傳遞上扮演重要角色。鈣調素(calmodulin)是一胞內鈣離子感受蛋白,可透過膜通道蛋白C端上高度保守性之蛋白序列IQ motif對許多不同類型之膜通道蛋白進行調控。前人的研究當中指出,鈣調素對於不同的類型鈉離子通道蛋白之IQ motif具有不同親和能力。本實驗當中,將鈣調素(CaM)以及失去正常鈣離子結合功能之突變型鈣調素(CaM1234)與電壓依賴型鈉離子通道(Nav1.4)同時表現於人類胚胎腎臟細胞(human embryonic kidney cells, HEK 293T),鈣調素(CaM)和突變型鈣調素(CaM1234)可增加流入細胞之鈉離子的電流量,且並不改變鈉離子通道Nav1.4其活化(activation)與不活化(inactivation)特性。提高pipette solution中鈣離子濃度至10μM,鈣調素和突變型鈣調素均會增加鈉離子電流,而鈣調素會縮短鈉離子通道由不活化(inactivation)狀態再回到通道可再開啟的時間。若降低pipette solution中鈣離子濃度至0.2μM,其通道蛋白由不活化狀態恢復至通道可再開啓的時間則不受影響。此外,鈣調素在Nav1.1上亦有類似的調控情形,會增加鈉離子的電流。 經由西方點墨法(western blot)已及細胞免疫染色的分析,發現細胞膜上鈉離子通道的表現量有增加的現象。另外,在IQ motif上進行點突變亦會觀察到上述兩項改變。實驗結果顯示鈣調素可藉由感應胞內鈣離子濃度的變化進一步調控電壓依賴型鈉離子通道之特性。Voltage-gated sodium channels (VGSCs) are essential for the initiation and propagation of action potentials in excitable cells. Calmodulin (CaM), a calcium sensor protein, regulates many types of ionic channels by binding to the highly conserved IQ motif at the intracellular C-terminal. Several reports have suggested that CaM has differential binding affinities with peptides containing the IQ motifs of various Na+ channels. However, it is not clear how CaM modulate the Na+ channel activities. In this report, we co-expressed CaM and Nav1.4 in 293T cells and measured the Na+ currents by patch-clamp technique in whole-cell mode. Both CaM and the Ca2+-binding deficient mutant, CaM1234, enhanced the current amplitude without changing the activation and inactivation properties. Elevating the Ca2+ concentration in the pipette solution to 10 μM, CaM and CaM1234 further increased the Na+ current; however, only CaM shortened the recovery time. While with 0.2 μM Ca2+ in the pipette solution, both CaM and CaM1234 enhanced the Na+ currents but had no effect on recovery time. Staining the expression level of Nav1.4 with a specific antibody, the amount of Nav1.4 at the plasma membrane was increaseed by CaM and CaM1234. Mutation in the IQ motif increased the Na+ current and recovery rates. CaM had a similar effect in enhancing the Nav1.1 currents. These findings suggest that CaM modulates VGSCs via the IQ motif in response to intracellular calcium concentration changes

    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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