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    CXCR4/CXCR7-CXCL11/CXCL12 AXIS PROMOTES MALIGNANT PHENOTYPE IN PUTATIVE STEM CELLS FROM HUMAN MENINGIOMAS

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    Meningioma is the most frequent primary tumor of the central nervous system. The greatest percentage of meningiomas is benign tumors (WHO grade I). However, although surgical and radiotherapy techniques have significantly improved over the years, some meningiomas, independently from the grading, are refractory to multimodality therapies, and recur and/or undergo malignant transformation, representing an unsolved therapeutic challenge. Therefore, beside histopathologic benign appearance, biologically aggressive meningiomas need to be molecularly characterized, to identify novel therapeutic targets. In malignant tumors, recurrence is mainly ascribed to the presence of cancer stem cells (CSCs) which are expression of tumor cell heterogeneity, and sustain tumorigenesis, metastasization and drug resistance. CSCs are characterized by stem cell marker expression, self-renewal, and ability to differentiate into tumor-specific cell types. Recently, CSCs and their functional role have been also studied in benign tumors, including meningioma. A range of genes and proteins have been proposed to identify meningioma stem-like cells, among them CD105, a transmembrane glycoprotein, involved in angiogenesis and in the progression of a variety of tumors. Stemness, as well as cancer cell aggressive behavior, is a cell property strictly linked to tumor microenvironment: reciprocal interactions between growth factors, cytokines and chemokines released by both CSCs and other cell types forming the niche, modulate each other to sustain tumor growth. Chemokine signaling, and the CXCL11/CXCL12-CXCR4/CXCR7 system in particular, drives cell proliferation and migration in several solid tumors. On these premises, this study is focused on the isolation and characterization of stem-like cells from post-surgical samples of human meningiomas, delving deeply into the role of this subpopulation in meningioma aggressive behavior. Moreover, we analyzed the contribution of CXCR4-7 receptors in the regulation of their biological properties. Twenty-eight primary cell cultures have been obtained from 35 meningiomas, and maintained in stem cell-permissive culture conditions to enrich in CSCs. Putative meningioma stem cells rapidly grow, form meningospheres and express stem markers, such as Sox2, NANOG, CD133 and Oct-4. Conversely, CD105 was not differentially expressed between stem-like cells and their “non-stem” counterpart, cells grown in serum-containing medium. Moreover, stem-like cells displayed high migratory capacity and in vitro angiogenic activity, supporting their malignant phenotype. Meningioma stem-like cells displayed a distinct chemokinereceptor profile from “non-stem” cell population, and selectively respond to in vitro CXCL11 and CXCL12 stimulation enhancing proliferation, migration and vascular mimicry. Pharmacological inhibition of individual CXCR4 or CXCR7 significantly impaired CXCL12- and CXCL11-induced proliferation, chemotaxis and vessel-like structure formation, therefore suggesting that these activities are mediated by both receptors. We speculated that these receptors act as heterodimers, formed upon ligand activation and that the blockade of one of them results in a complete inhibition of biological effects. Overall our results, collected from a large number of meningioma cell cultures derived from different patients, allow the identification of a tumor subpopulation endowed with comm on stem cell-like features, and suggest that both CXCR4 and CXCR7 signaling sustains meningioma stem cell phenotype. Prospectively, the isolation and culture of stem-like cells directly from the meningioma tissues will allow to test new therapeutic compounds to block meningioma growth and invasiveness, in particular for those tumors showing an unpredictable aggressive behavior. In this context, we propose that the CXCR4-7 chemokinergic system might represent a relevant pharmacological target

    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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