1,721,175 research outputs found

    Development of conditionally replicating integrase defective lentiviral vectors for Epstein-Barr virus gene therapy

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    Integrase defective lentiviral vectors show promise for achieving gene expression without integration, preserving some benefits of LVs, whereas reducing the potentially detrimental risk of insertional mutagenesis. Numerous reports supported the ability of these vectors to confer long-term gene expression in slowly dividing cell types for potentially corrective gene expression. These reports also highlighted additional applications of these vectors as delivery platforms for alternate integrative pathways, suicide gene therapy and vaccines. Nevertheless, in cell culture systems the transgene expression duration of IDLVs is highly transient, because of the rapid cell turnover, limiting their use to non-dividing or slowly dividing cells. The instability of the IDLVs in proliferating cells is mainly due to the lack of an origin of replication allowing vector’s DNA replication. In a work by Vargas et al. (2008), it has been demonstrated that if the transgene cassette carries a viral ORI, IDLV’s transgene expression persists if the necessary trans protein is supplied. In the work described in this thesis we have engineered IDLVs to selectively transduce EBNA1-expressing cells by incorporating the EBV oriP into the IDLV genome. Exploitation of EBNA1 to maintain DNA that contains the oriP has obvious use for gene therapy. Epstein–Barr virus (EBV) is widely associated with disease in both immunocompromised and immunocompetent hosts and has been implicated in approximately 1% of tumors worldwide. Current therapies are poorly effective and often toxic, therefore, the development of an effective, tumor-specific treatment is of high priority. The goal of IDLV-mediated suicide gene therapy of EBV-driven diseases would be to eliminate B cells that are latently infected with EBV using an IDLV that contains the EBV elements required for EBNA1-induced episome retention and transcriptional up-regulation.This work was sponsored by Fondazione Italiana Sclerosi Multipla (FISM

    Eye Pathology

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    The conjunctiva is a thin and moist mucous membrane. It covers the anterior part of the eye, save for the cornea, reaches peripherally into the upper and lower fornices, and then reflects to outline the inner surface of the eyelids

    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

    25-Gauge Pars Plana Vitrectomy for Retained Lens Fragments in Complicated Cataract Surgery

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    To verify the efficacy of 25-gauge pars plana vitrectomy (PPV) for the management of posteriorly dislocated lens material after complicated cataract extraction and to determine in what patients this approach offers the optimal benefit in terms of efficacy and safety, considering the amount of retained nuclear material and the duration of surgery

    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
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