1,720,970 research outputs found
“Modulazione dell'espressione genica in cellule linfoidi ed epitelioidi infettate con il Virus Erpetico Umano 8 (HHV8) ed analisi dell’attività chemioterapica/antivirale della Distamicina A (DA)”
Get PDFPurpose of this PhD study have been the analysis of the modulation of cellular gene by Human Herpes virus 8 (HHV8) infection and of the potential antiviral effect of Distamycin A (DA), an oligopeptidic antibiotic. This study describes a comprehensive picture of global gene changes soon after HHV-8 active infection of two susceptible cell types. We found that host cell expression changes after only 24 hours of infection, and it is quite different from previous gene induction studies that were carried out at later time points of virus infection. In fact, Poole et al. have used a different primary effusion lymphoma cell line (JSC1) to produce the virus that was used to infect primary endothelial cells for a period of 3–5 weeks, and gene array experiments were done when almost all of the cells changed from typical cobblestone to spindle-shaped morphology and were positive for LANA. Several features were apparent from these analysis: a) there was virtually non-overlapping list of genes in all of two viral subtypes analyzed; b) HHV-8-induced transcriptional profiles in the epithelial and PBMC were closely different. This is probably because the criteria of > 4-fold gene induction as significant is a threshold filter very tight. Nevertheless, the genes that emerge from such comparison will be of greater interest for studying their role in the unique biology of HHV-8. Furthermore, the replicative capacity of the two different strains in the two cell types and the modulation of cell involved in the inflammatory process would seem to indicate that the genotypic difference could be translated into a different virus-host relationship, also attributable to a different pathogenetic mechanism. In addition to identifying specific host response genes within each functional pathway that are already known to be important for HHV-8 infection, our findings identify novel candidate genes that are not yet known in HHV-8 biology.
Obtained results show a lack of cytotoxicity of DAlipo on cultured HEK293, RCE and PBMC cells. It might be noted that the CC50 value found in the present study falls at the low extreme of the range of CC50 values reported in the literature. In fact, available data show CC50 values ranging from 35 μM in a Hep-2 cell line to 154 μM in a HeLa cell line and 385 μM in rabbit primary kidney cells. It has been reported that DA inhibits the activity of all DNA polymerases. This mechanism of action could explain its antiviral activity. Because of the lack of information concerning the relevant genetic definition of HHV8 A1 and C3 subtypes from BCBL1 and BC3 cell lines, whether the observed behavior be the result of the expression of specific mutated genes or a non specific consequence of viral strain virulence has to be established. Clearly, further studies are needed to explain the different degree of sensitivity of HHV8 subtypes to DA and Dalipo. The significant antiviral activity of DAlipo and the lack of citotoxicity in epithelial and lymphoid cell lines shown in the present study indicates the compound as an antiherpetic drug potentially useful in both topic and systemic treatments. It could be used either alone or in association with other antiviral treatment, the latter to be employed at lower dosages and for shorter periods of time, thus limiting side effects. The antiviral activity of DAlipo formulation also in lymphoid cell lines may be due to the hydrophobic or amphiphilic drug penetration efficacy increased through inclusion of the drug in liposomes. DAlipo showed, when compared with the free drug, higher antiviral activity against HHV8 A1 and C3 subtypes in PBMCs and might therefore represent a promising DA formulation that could be used also for systemic treatments
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Liposomes as a potential ocular delivery system of distamycin A
Get PDFLiposomes containing Distamycin A (DA) may be clinically useful in the treatment of ocular HSV infections, especially in acyclovir-resistant HSV keratitis. This study evaluated the in vitro and in vivo performance of a topical controlled release liposomal formulation containing DA (DA-Lipo) aimed at reducing the toxicity of the encapsulated active agent and improving drug uptake by ocular tissues. The bioavailability of DA in the tear fluid and the DA uptake into the cornea were increased after instillation of DA-Lipo in rabbits, reaching the DA corneal concentration corresponding to IC50 values against HSV without any sign of transcorneal permeation of drug. DA-Lipo was definitely less cytotoxic then plain DA in rabbit corneal epithelial cells. These results provide new insights into the correlation between the in vitro data and the drug kinetics following ocular applications of liposomal vesicle
Variations on the Author
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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