1,723,212 research outputs found
Book review: Religion in the Anthropocene, edited by Celia Deane-Drummond, Sigurd Bergmann and Markus Vogt. Eugen, OR.: Cascade Books, 2017. 338pp. ISBN 978-1-4982-9191-0
No full textBook review of Celia Deane-Drummond, Sigurd Bergmann and Markus Vogt (eds), Religion in the Anthropocene
Eugen, OR.: Cascade Books, 2017. 338pp. ISBN 978-1-4982-9191-0
Role of Cathepsin A and Lysosomes in the Intracellular Activation of Novel Antipapillomavirus Agent GS-9191
No full textABSTRACT
GS-9191, a bis-amidate prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)-N
6
-cyclopropyl-2,6-diaminopurine (cPrPMEDAP), was designed as a topical agent for the treatment of papillomavirus-associated proliferative disorders, such as genital warts. In this study, we investigated the mechanism of conversion of GS-9191 to cPrPMEDAP. We observed that GS-9191 is hydrolyzed in the presence of the lysosomal carboxypeptidase cathepsin A (CatA)
in vitro
and is less efficiently metabolized in CatA-deficient fibroblasts than in control cells. In addition, knockdown of CatA by small interfering RNA (siRNA) reduced the intracellular accumulation of GS-9191 metabolites. However, intracellular CatA levels did not correlate with the susceptibility of tested cell lines to GS-9191, indicating that the CatA step is unlikely to be rate limiting for the activation of GS-9191. Further analysis showed that upon the hydrolysis of the carboxylester bond in one of the GS-9191 amidate moieties, the unmasked carboxyl group displaces
l
-phenylalanine 2-methylpropyl ester from the other amidate moiety. The cPrPMEDAP–
l
-phenylalanine conjugate (cPrPMEDAP-Phe) formed is not metabolized by Hint1 (histidine triad nucleotide binding protein 1) phosphoramidase but undergoes spontaneous degradation to cPrPMEDAP in acidic pH that can be significantly enhanced by the addition of SiHa cell extract. Pretreatment of SiHa cells with bafilomycin A or chloroquine resulted in an 8-fold increase in the intracellular concentration of cPrPMEDAP-Phe metabolite and the accumulation of GS-9191 metabolites in the lysosomal/endosomal fraction. Together, these observations indicate that the conversion of GS-9191 to cPrPMEDAP occurs in lysosomes via CatA-mediated ester cleavage, followed by the release of cPrPMEDAP, most likely through the combination of enzyme-driven and spontaneous pH-driven hydrolysis of a cPrPMEDAP-Phe intermediate.
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Book review: Religion in the Anthropocene, edited by Celia Deane-Drummond, Sigurd Bergmann and Markus Vogt. Eugen, OR.: Cascade Books, 2017. 338pp. ISBN 978-1-4982-9191-0
No full textThis is the author accepted manuscript. The final version is available from Paternoster Periodicals via the link in this recordBook review of Celia Deane-Drummond, Sigurd Bergmann and Markus Vogt (eds), Religion in the Anthropocene
Eugen, OR.: Cascade Books, 2017. 338pp. ISBN 978-1-4982-9191-0
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
Comparação de critérios de medição e qualidade de sacos para lixo utilizando parâmetros metrológicos e a norma brasileira ABNT NBR 9191 / Comparison of measurement criteria and quality of garbage bags using metrological parameters and the Brazilian standard ABNT NBR 9191
No full textDiante da acirrada disputa no mercado internacional, todas as indústrias buscam garantir a qualidade de seus produtos com o menor custo possível, aumentando assim a disseminação dos conceitos de metrologia que atendam a esses requisitos. Uma forma de garantir a qualidade dos produtos é o emprego da metrologia industrial no processo produtivo. Podemos ver os sacos de lixo como produtos essenciais do dia a dia, sendo um produto regulamentado pela norma NBR 9191. O principal ponto deste trabalho é a análise da medição e qualidade das dimensões do saco de lixo, tendo como base parâmetros metrológicos e a norma ABNT NBR 9191. O instrumento de medida utilizado foi uma régua graduada com resolução de 1 mm, ou 0,1 cm. Diante da comparação dos resultados de medição, foi evidenciado que pela norma e pelas técnicas de metrologia, os lotes foram aprovados
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
GS-9191 is a novel topical prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine with antiproliferative activity and possible utility in the treatment of human papillomavirus lesions
Full text linkGS-9191 is a novel double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl)guanine (PMEG) designed as a topical agent to permeate skin and be metabolized to the active nucleoside triphosphate analog in the epithelial layer. The prodrug was shown to be metabolized intracellularly to 9-(2-phosphonylmethoxyethyl)-N(6)-cyclopropyl-2,6,diaminopurine (cPrPMEDAP) and subsequently deaminated to PMEG. The active form, PMEG diphosphate, was shown to be a potent inhibitor of DNA polymerase alpha and beta while showing weaker activity against mitochondrial DNA polymerase gamma (50% enzyme inhibition observed at 2.5, 1.6, and 59.4 microM, respectively). GS-9191 was markedly more potent than PMEG or cPrPMEDAP in a series of human papillomavirus (HPV)-positive cell lines, with effective concentrations to inhibit 50% cell growth (EC(50)) as low as 0.03, 207, and 284 nM, respectively. In contrast, GS-9191 was generally less potent in non-HPV-infected cells and primary cells (EC(50)s between 1 and 15 nM). DNA synthesis was inhibited by GS-9191 within 24 h of treatment; cells were observed to be arrested in S phase by 48 h and to subsequently undergo apoptosis (between 3 and 7 days). In an animal model (cottontail rabbit papillomavirus), topical GS-9191 was shown to decrease the size of papillomas in a dose-related manner. At the highest dose (0.1%), cures were evident at the end of 5 weeks, and lesions did not recur in a 30-day follow-up period. These data suggest that GS-9191 may have utility in the treatment of HPV-induced lesions.sponsorship: The work of N.D. Christensen was supported in part by NIH grants NO1 AI15435 (Utah State University; subcontract to Penn State College of Medicine) and NIAID AI30045. R. Snoeck and G. Andrei are recipients of the following grants: Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO), grant G.0404.06, and Geconcerteerde Onderzoeksacties, grant G.00/12. (NIH|NO1 AI15435, NIAID|AI30045, Fonds voor Wetenschappelijk Onderzoek-Vlaanderen (FWO)|G.0404.06, Geconcerteerde Onderzoeksacties|G.00/12)status: Publishe
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
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