1,720,958 research outputs found

    Repositioning of drugs for cryptococcosis: experimental evaluation of duloxetine hydrochloride in Cryptococcus neoformans and Cryptococcus gattii

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    Infecções fúngicas como as causadas por Cryptococcus spp. são de alta mortalidade e morbidade. O reposicionamento de fármaco, ou seja, a utilização de compostos para finalidade diferente da qual esse foi desenvolvido, pode ser uma alternativa para identificar fármacos mais eficazes. Assim, este estudo tem como propósito avaliar a atividade antifúngica, in vitro e in vivo, do fármaco cloridrato de duloxetina (CD), antidepressivo pertencente a classe dos Inibidores Seletivos da Recaptação da Serotonina e Norepinefrina frente a cepas padrões e clínicas de Cryptococcus neoformans e C. gattii. Foi utilizada a técnica de microdiluição de acordo com o European Committee on Antimicrobial Susceptibility Testing (EUCAST) para determinar a Concentração Inibitória Mínima (MIC), e a técnica do “tabuleiro de xadrez” para avaliar o efeito sinérgico de anfotericina B (AmB) em associação com CD. Além disso, foi avaliado o efeito de CD na quantidade do ergosterol. O efeito do CD também foi avaliado em biofilmes de C. neoformans e C. gattii, analisando a biomassa por cristal violeta, a viabilidade celular por XTT e morfologia através das imagens de Microscopia Eletrônica de Varredura (MEV). In vivo, a eficácia de CD foi avaliada por curvas de sobrevivência no modelo invertebrado Galleria mellonella. CD foi ativo frente a todas as cepas clínicas e padrões de C. neoformans e C. gattii, apresentando valores de CIM e CFM na faixa de 15,62 – 62,5 µg/mL. A combinação de CD com AmB apresentou uma combinação sinérgica, reduzindo o valor da CIM em 4 vezes tanto para CD quanto para AmB. CD não produziu redução na quantidade de ergosterol presente na membrana de C. gattii ATCC e C. neoformans ATCC. Em biofilmes, foi observada a redução da biomassa do biofilme em até 82,16% e redução de 99,6% na viabilidade celular de C. gattii. Em biofilmes de C. neoformans a redução foi de 81,13% e 99,5% respectivamente para a análise de biomassa e viabilidade. As imagens de MEV corroboraram com os achados dos ensaios realizados para análise do efeito de CD em biofilmes. Em G. mellonella aumentou a sobrevivência da larva quando utilizado na concentração de 3,125 mg/larva. Assim, os ensaios validaram a hipótese de que o cloridrato de duloxetina tem ação antifúngica e antibiofilme in vitro frente a cepas clínicas e cepas padrões de C. neoformans e C. gattii.Fungal infections such as those caused by Cryptococcus spp. are of high mortality and morbidity. Drug repositioning, that is, the use of compounds for a purpose different from the one for which it was developed, can be an alternative to identify more effective drugs. Thus, this study aims to evaluate the antifungal activity, in vitro and in vivo, of the drug duloxetine hydrochloride (CD), an antidepressant belonging to the class of Selective Serotonin and Norepinephrine Reuptake Inhibitors against standard and clinical strains of Cryptococcus neoformans and C. gattii. The microdilution technique according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) was used to determine the Minimum Inhibitory Concentration (MIC), and the “chessboard” technique was used to evaluate the synergistic effect of amphotericin B (AmB) on association with CD. In addition, the effect of CD on the amount of ergosterol was evaluated. The effect of CD was also evaluated in C. neoformans and C. gattii biofilms, analyzing the biomass by crystal violet, cell viability by XTT and morphology through Scanning Electron Microscopy (SEM) images. In vivo, the effectiveness of CD was evaluated by survival curves in the Galleria mellonella invertebrate model. CD was active against all clinical strains and patterns of C. neoformans and C. gattii, with MIC and CFM values in the range of 15.62 – 62.5 µg/mL. The combination of CD with AmB showed a synergistic combination, reducing the MIC value by 4 times for both CD and AmB. CD did not produce a reduction in the amount of ergosterol present in the membrane of C. gattii ATCC and C. neoformans ATCC. In biofilms, a reduction in biofilm biomass of up to 82.16% and a 99.6% reduction in cell viability of C. gattii were observed. In C. neoformans biofilms the reduction was 81.13% and 99.5% respectively for biomass and viability analysis. The SEM images corroborated the findings of the tests carried out to analyze the effect of CD on biofilms. In G. mellonella, larval survival increased when used at a concentration of 3.125 mg/larvae. Thus, the tests validated the hypothesis that duloxetine hydrochloride has antifungal and antibiofilm action in vitro against clinical strains and standard strains of C. neoformans and C. gattii.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

    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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    Nao informado

    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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