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    FOXP3 EXPRESSION IN BREAST CARCINOMA CELLS AND METASTATIC SPREAD

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    Forkhead box P3 (FOXP3), a gene member of the forkhead/winged-helix family of transcription regulators, is implicated in regulating immune system development and function. This gene has been found to be of crucial importance for the generation of CD4+CD25+ regulatory T cells (Tregs). Tregs express both the full-length FOXP3 and Δ2FOXP3 natural splice variant. In addition to its expression in the lymphocyte lineage, studies have recently described FOXP3 expression in non-hematopoietic-derived cells, including cancerous or normal epithelial cells of multiple lineages and origins. The role of FOXP3 in cancer cells is still unclear. Our immunohistochemical (IHC) and statistical analyses of archival material from two old series of breast cancer patients indicated that the expression of FOXP3 in tumor cells is an independent strong prognostic factor for distant metastases. The impact of FOXP3 on patient survival has been confirmed by our IHC analysis on chemotherapy-treated breast cancer patients. In fact, FOXP3 positive patients had poorer disease-free survival compared to FOXP3-negative patients. To investigate FOXP3 role in breast cancer, its expression was assessed in a panel of breast carcinoma cell lines and in human primary breast carcinoma samples by Western blot analyses. Full lenght FOXP3 was detected in all human breast cancer samples and breast cancer cell lines analyzed, whereas the Δ2FOXP3 isoform was visible solely in human breast tumors. The involvement of ∆2FOXP3 in breast cancer and the possibility that this isoform could have a different role from that of full length FOXP3 in breast cancer progression has been investigated. WTFOXP3 or ∆2FOXP3 overexpression was induced in MDA-MB-231 breast cancer cell line. Both WTFOXP3 and Δ2FOXP3 overexpression significantly increased in vitro migration and invasion capability of breast cancer cells, whilst inhibiting breast cancer cell proliferation. Taking advantage of these in vitro results and to further investigate in vivo role of FOXP3 in breast cancer metastasis, the metastatic capability of WTFOXP3- or Δ2FOXP3-overexpressing MDA-MB-231 breast cancer cells was investigated. The mean number of spontaneous lung metastases was superimposable in WTFOXP3- and Δ2FOXP3-overexpressing tumor bearing mice (mean±SD: 12.5±27.4 and 10.3±18.1, for WTFOXP3- and Δ2FOXP3-MDA-MB-231-injected mice, respectively). These findings do not support a role of Δ2FOXP3 isoform in promoting breast cancer metastasis. In our IHC analyses of breast carcinoma specimens subcellular staining of FOXP3 was observed to be cytoplasmic or cytoplasmic/nuclear. Since the role of FOXP3 is transcription regulation, which mainly occurs in the nucleus, a cytoplasmic FOXP3 localization could affect its biological role. Thus the hypothesis that FOXP3 in tumor cells may have distinct biological activities and prognostic values according to its subcellular localization was investigated. Metastatic capability of two breast cancer cell clones with inducible FOXP3 expression and with different FOXP3 subcellular localization was evaluated. FOXP3 overexpression in breast cancer cells with a predominantly nuclear FOXP3 localization led to a significant reduction in the number of both spontaneous and experimental lung metastases compared to controls (mice in which FOXP3 overexpression was not induced). Contrarily, in mice injected with breast cancer cells which showed a predominantly cytoplasmic FOXP3 localization, FOXP3 overexpression in tumor cells led to a significant increase in the number of lung metastatic lesions compared to control group. These results suggested that nuclear FOXP3 localization enable its transcriptional activity, resulting in an onco-suppressive effect, while its cytoplasmic localization unable this transcription factor to perform its biological functions, resulting in an opposite in vivo effect. Our findings indicate that FOXP3 subcellular localization in breast tumor cells is an important determinant of prognosis, supporting the involvement of this transcription factor in breast cancer metastasis. Additional studies are in progress to confirm these data and to better understand the molecular mechanisms involved in FOXP3 role in driving breast cancer metastasis

    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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