1,721,001 research outputs found
Construction and characterization of infectious inter-genotypic Hepatitis C Virus chimeras
Full text linkA major impediment in Hepatitis C Virus (HCV) research and drug development has been the lack of a culture system supporting virus production. This obstacle was recently overcome by using JFH1-based full-length genomes that allow the production of infectious viruses both in vitro and in vivo. Despite such improvement, the system was restricted to two structural gene sequences (JFH1 and J6), both derived from the genotype 2a, limiting comparative studies between different HCV strains. The system was thus extended by the creation of a series of inter-genotypic HCV chimeras that allow the production of infectious genotypes 1a, 1b and 3a particles, even if with a less efficiency in terms of productivity compared with the wild type JFH1 strain.
In the present study, based on the JFH1 strain, we generated two novel chimeric HCV constructs in which only the sequences encoding for the E1 and/or E2 glycoprotein ectodomains are substituted from JFH1 to the Con1 strain (genotype 1b). The entire structural region is maintained of the infectious strain JFH1, with the exception of the soluble portion of E1 and/or E2, allowing comparative analysis of the impact of such regions on virus morphogenesis.
Both JFH1/Con1E1E2 and JFH/Con1E2 chimeric constructs are able to replicate in hepatic cells. Importantly, we demonstrate for the first time that the E1E2 heterodimer formation is not hampered by the ectodomain swapping since glycoproteins from genotypes 2a and 1b can correctly interact each other. Nevertheless, none of the chimeric constructs allow the production of infectious viral particles. This evidence first suggests a specific role of E1 and E2 glycoproteins in HCV particle morphogenesis, and it is corroborated by several experiments. In particular we examined the JFH/Con1E2 construct, in which only the E2 ectodomain region is swapped from genotype 2a to 1b, by confocal microscopy analysis, trans-complementation experiments and by evaluating the presence of HCV infectious particle precursor within transfected cells. Overall our data provide strong evidences that the E2 ectodomain is involved in the HCV assembly through a genotype-specific interplay with the remaining viral structural proteins. As consequence, in the case of inter-genotypic chimeras, genetic incompatibility between JFH1 backbone and the E2 structural protein of genotype 1b dramatically affects the production of viral particles in our system. One of the most likely involved protein in such interactions seems to be NS2, the role of which was recently demonstrated as crucial in the HCV assembly/release processes. However this remains a hypothesis that needs to be verified in order to define the relationships among HCV proteins.Il maggior ostacolo allo sviluppo di terapie anti HCV è rappresentato dalla mancanza di culture cellulari che supportano efficacemente la produzione di virus. Questo ostacolo è stato recentemente superato grazie all’isolamento di un clone, denominato JFH1 (genotipo 2a), il cui genoma porta alla produzione di particelle virali infettive sia in vitro che in vivo. Anche se tale sistema cellulare (HCVcc) rappresenta un’importante conquista, presenta il grosso limite della dipendenza dal subtipo JFH1 e da una chimera intra-genotipica in cui la regione strutturale deriva dal subtipo J6, comunque di genotipo 2a. Per effettuare studi comparativi su diversi genotipi, sono stati quindi ingegnerizzati virus chimerici inter-genotipici in cui la prima metà del genoma di JFH1 (dal 5’- UTR alla proteina NS2) è stata sostituita con l’analoga regione proveniente da altri genotipi.
Nel presente lavoro sono state costruite due chimere inter-genotipiche con una nuova strategia. A differenza delle precedenti, la regione strutturale è stata mantenuta interamente di JFH1, ad eccezione della porzione solubile (ectodominio) di una o entrambe le proteine dell’envelope E1 e E2. In questo modo è stato possibile analizzare il ruolo di tale regione, ed in particolare dell’ectodominio di E2, nella produzione di particelle infettive di HCV.
I risultati riportati dimostrano per la prima volta che proteine dell’envelope derivanti da genotipi diversi (nello specifico E1 di genotipo 2a ed E2 di genotipo 1b) possono correttamente interagire a formare dimeri E1E2, rappresentanti la forma funzionale delle proteine dell’envelope. Ciononostante nessuno dei due costrutti chimerici prodotti ha portato all’ottenimento di particelle virali infettive, indicando la presenza di determinanti all’interno della porzione sostituita importanti per la produzione di HCV. In particolare, grazie ad esperimenti di microscopia confocale, analisi della presenza di precursori virali all’interno delle cellule trasfettate ed esperimenti di trans-complementazione, per la prima volta dimostriamo che la regione ectodominica della proteina dell’envelope E2 è fortemente implicata nell’assemblaggio di nuovi virioni, probabilmente attraverso interazioni genotipo-specifiche con altre proteine strutturali. Di conseguenza, nel nostro sistema, la produzione di particelle virali risulta drasticamente alterata a causa dell’incompatibilità genetica tra il backbone JFH1 e la porzione ectodominica di E2 derivante da genotipo 1b. Dato che recentemente è stato riportato un ruolo chiave per NS2 nel processo di assemblaggio, la nostra ipotesi è che una delle interazioni genotipo-specifiche richieste coinvolga per l’appunto E2 nella sua regione solubile e la proteina non strutturale NS2. Quest’ipotesi rimane comunque da approfondire con ulteriori esperimenti atti a meglio definire il tipo di relazione tra proteine virali e il ruolo di tali interazioni nell’assemblaggio di nuovi virioni
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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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