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    Study of the modulation of humoral and cellular immune response induced by Mayaro and Chikungunya in co-infected mice.

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    O aumento recente dos surtos epidêmicos de arboviroses no Brasil, como no caso o vírus da Zika (ZIKV), Dengue (DENV), Febre amarela (YFV) e Chikungunya (CHIKV), têm causado sérios problemas de saúde pública. Esse aumento faz com que outros arbovírus circulantes menos conhecidos, como o vírus Mayro (MAYV), sejam negligenciados. A presença desses diferentes arbovírus em áreas onde o MAYV cocircula, aumenta o risco de coinfecção durante os períodos de surtos. Apesar de haver relatos de coinfecção MAYV com outros arbovírus, há poucos estudos reportando a coinfecção MAYV e CHIKV. Tanto o CHIKV como o MAYV, pertencem ao gênero Alphavirus, e devido à proximidade antigênica, os sintomas clínicos são similares, interferindo no diagnóstico sorológico. Estudos recentes mostraram que a infecção com alphavírus desencadeia em indivíduos expostos, uma potente resposta humoral capaz de conferir proteção contra uma reinfecção. Utilizando modelo murino, foi demonstrado que camundongos expostos previamente ao CHIKV apresentam uma proteção parcial cruzada, mediada pela resposta imune inata, à infecção pelo MAYV. No entanto, ainda há lacunas no que diz respeito ao entendimento da resposta por anticorpos bem como o papel das células B na imunidade contra esses alphavirus. Nesse estudo, o primeiro objetivo foi estudar de que forma a resposta imune humoral e celular é modulada na pata de camundongos infectados com MAYV e CHIKV. Camundongos C57BL/6 adultos imunologicamente competentes, foram infectados na pata nas seguintes condições: 1. simultâneo (CHIKV+MAYV); 2. infecção com MAYV e 7 dias depois com CHIKV (1st MAYV+CHIKV(D7)); 3. infecção com CHIKV e 7 dias depois com MAYV (1st CHIKV+MAYV(D7)); 4. infecção com MAYV e 14 dias depois com CHIKV (1st MAYV+CHIKV(D714)); 5. infecção com CHIKV e 14 dias depois com MAYV (1st CHIKV+MAYV(D14)). A infecção simultânea reduziu a carga viral na almofada plantar (bioluminescência) e reduziu o pico de inchaço na pata no dia 6 pós-infecção. No entanto, observamos um aumento na infiltração celular no nódulo linfático, caracterizado pelo aumento nas células CD4, CD8, DC e B. Com relação a pata, foi observado um aumento nas populações de células B e NK. A infecção prévia de 7 ou 14 dias com MAYV, parece ter induzido uma resposta imune capaz de interferir na replicação do CHIKV, pois não observamos carga viral na almofada plantar (bioluminescência) e o pico de inflamação foi reduzido no dia 7 pós-infecção. A infiltração celular também foi reduzida tanto na pata quanto no linfonodo poplíteo (pLN), com níveis semelhantes ao grupo naive. Resultados semelhantes foram observados na infecção prévia de 7 ou 14 dias com CHIKV. Com relação aos títulos de IgM e IgG E2.1 CHIKV-específicos, todos os grupos infectados mantiveram níveis consideráveis de IgM no dia 21 pós-infecção, independente dos altos títulos de IgG observados. Na segunda parte do projeto estudamos a eficácia de dois candidatos vacinais em desafio homólogo: 1) candidato vacinal para CHIKV, a E2.1, que se encontra encapsulada em nanopartículas (NMVs) que contém MPLA acoplado a sua estrutura, e 2) candidato vacinal para MAYV, baseado em partículas semelhante a vírus (do inglês virus-like protein VLP). Ambos candidatos vacinais foram capazes de reduzir a viremia e previnir o inchaço na pata induzido pela infecção com CHIKV ou MAYV.The recent increase in epidemic outbreaks of arboviruses in Brazil, such as Zika virus (ZIKV), Dengue (DENV), Yellow fever (YFV), and Chikungunya (CHIKV), has caused serious public health issues. This rise has led to the neglect of other lesser-known circulating arboviruses, such as Mayaro virus (MAYV). The presence of these different arboviruses in areas where MAYV co-circulates increases the risk of co-infection during outbreak periods. Despite reports of MAYV co-infection with other arboviruses, there are few studies documenting co-infection of MAYV and CHIKV. Both CHIKV and MAYV belong to the Alphavirus genus, and due to their antigenic proximity, the clinical symptoms are similar, complicating serological diagnosis. Recent studies have shown that infection with alphaviruses triggers a potent humoral response in exposed individuals, capable of providing protection against reinfection. Using a murine model, it has been demonstrated that mice previously exposed to CHIKV exhibit partial cross-protection, mediated by the innate immune response, against MAYV infection. However, there are still gaps in understanding antibody responses as well as the role of B cells in immunity against these alphaviruses. In this study, the first objective was to investigate how the humoral and cellular immune responses are modulated in the paws of mice infected with MAYV and CHIKV. Immunologically competent adult C57BL/6 mice were infected in the paw under the following conditions: 1. simultaneous (CHIKV+MAYV); 2. infection with MAYV followed by CHIKV after 7 days (1st MAYV+CHIKV(D7)); 3. infection with CHIKV followed by MAYV after 7 days (1st CHIKV+MAYV(D7)); 4. infection with MAYV followed by CHIKV after 14 days (1st MAYV+CHIKV(D714)); 5. infection with CHIKV followed by MAYV after 14 days (1st CHIKV+MAYV(D14)). The simultaneous infection reduced the viral load in the plantar region of the paw (bioluminescence) and decreased the peak swelling in the paw on day 6 post-infection. However, we observed an increase in cellular infiltration in the lymph node, characterized by an increase in CD4, CD8, DC, and B cells. Regarding the paw, there was an increase in the populations of B and NK cells. Prior infection with MAYV for 7 or 14 days seems to have induced an immune response capable of interfering with CHIKV replication, as no viral load was observed in the plantar pad (bioluminescence) and the peak of inflammation was reduced on day 7 post-infection. Cellular infiltration was also reduced in both the paw and the pLN, with levels similar to the naive group. Similar results were observed following prior infection with CHIKV for 7 or 14 days. Concerning the IgM and IgG E2.1 CHIKV-specific titers, all infected groups maintained considerable levels of IgM on day 21 post-infection, regardless of the high IgG titers observed. In the second part of the project, we studied the efficacy of two vaccine candidates in homologous challenge: 1) a vaccine candidate for CHIKV, E2.1, encapsulated in nanoparticles (NMVs) containing MPLA attached to its structure, and 2) a vaccine candidate for MAYV based on virus-like particles (VLP). Both vaccine candidates were able to reduce viremia and prevent swelling in the paw induced by infection with CHIKV or MAYV

    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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