1,726,502 research outputs found
Aryl hydantoin Ro 13-3978, a broad-spectrum antischistosomal
Full text linkObjectives Praziquantel is the only drug available for the treatment of schistosomiasis and the state of the exhausted drug discovery pipeline is alarming. We restarted investigations on the abandoned antischistosomal Ro 13-3978, an aryl hydantoin discovered in the early 1980s by Hoffmann La-Roche. Methods Newly transformed schistosomula and adult Schistosoma mansoni were studied in the presence of Ro 13-3978 in vitro. The metabolic stability of Ro 13-3978 was determined in vitro using human and mouse liver S9 fractions. Dose-response relationship, stage specificity, hepatic shift and scanning electron microscopy studies were carried out in S. mansoni-infected mice. In addition, efficacy experiments were conducted in rodents infected with Echinostoma caproni and Fasciola hepatica as well as in S. mansoni-infected immunocompromised nude (Foxn1nu) mice. Results Ro 13-3978 showed minor in vitro activity and no damage to the tegument was found. No cytotoxicity was detected for Ro 13-3978. Ro 13-3978 was metabolically stable. ED50 values of 138.9 and 14.6 mg/kg were calculated for the treatment of juvenile and adult S. mansoni infections, respectively, with a single oral dose of Ro 13-3978. SEM studies revealed severe damage to the worms 48 h post-treatment of infected mice. A single oral dose of Ro 13-3978 (100 mg/kg) administered to S. mansoni-infected (Foxn1nu) mice reduced the worm burden by 88%. Ro 13-3978 was not active against E. caproni and F. hepatica in vivo. Conclusions Ro 13-3978 has excellent antischistosomal properties in vivo. Structure-activity relationship studies with the aryl hydantoins have been launched in order to elucidate active pharmacophores, further investigate the mechanism of action and to identify a derivative with minimal antiandrogenic effect
Aryl hydantoin Ro 13-3978, a broad-spectrum antischistosomal
No full textPraziquantel is the only drug available for the treatment of schistosomiasis and the state of the exhausted drug discovery pipeline is alarming. We restarted investigations on the abandoned antischistosomal Ro 13-3978, an aryl hydantoin discovered in the early 1980s by Hoffmann La-Roche.; Newly transformed schistosomula and adult Schistosoma mansoni were studied in the presence of Ro 13-3978 in vitro. The metabolic stability of Ro 13-3978 was determined in vitro using human and mouse liver S9 fractions. Dose-response relationship, stage specificity, hepatic shift and scanning electron microscopy studies were carried out in S. mansoni-infected mice. In addition, efficacy experiments were conducted in rodents infected with Echinostoma caproni and Fasciola hepatica as well as in S. mansoni-infected immunocompromised nude (Foxn1(nu)) mice.; Ro 13-3978 showed minor in vitro activity and no damage to the tegument was found. No cytotoxicity was detected for Ro 13-3978. Ro 13-3978 was metabolically stable. ED50 values of 138.9 and 14.6 mg/kg were calculated for the treatment of juvenile and adult S. mansoni infections, respectively, with a single oral dose of Ro 13-3978. SEM studies revealed severe damage to the worms 48 h post-treatment of infected mice. A single oral dose of Ro 13-3978 (100 mg/kg) administered to S. mansoni-infected (Foxn1(nu)) mice reduced the worm burden by 88%. Ro 13-3978 was not active against E. caproni and F. hepatica in vivo.; Ro 13-3978 has excellent antischistosomal properties in vivo. Structure-activity relationship studies with the aryl hydantoins have been launched in order to elucidate active pharmacophores, further investigate the mechanism of action and to identify a derivative with minimal antiandrogenic effects
Union Pacific (UP) 7863 & 3978
No full textA photograph print showing Union Pacific (UP) 7863, 4-8-2, and 3978, 4-6-6-4, on 1st section of passenger train No. 17, leaving Huntington, OR, 14 cars, 30 mph
Expression of both poly r(C) binding protein 1 (PCBP1) and miRNA-3978 is suppressed in peritoneal gastric cancer metastasis
No full textAbstractThe expression of legumain which has been shown overexpressed in patients with metastatic gastric cancer is positively correlated to both disease progression and outcome, and negatively correlated to microRNA (miR)−3978 expression. The RNA-binding protein, poly r(C) binding protein 1 (PCBP1) was the most downregulated protein in the metastatic tissue specimens. Quantitative real-time PCR showed that PCBP1 expression is transcriptionally downregulated in peritoneal metastasis tissues. RNA immunoprecipitation experiments showed that PCBP1 and miR-3978 are sequestered in normal peritoneal tissue, but the complex is disrupted following metastatic progression. PCBP1 expression mimicked miR-3978 expression across gastric cancer patients. Finally, replenishment of PCBP1 or miR-3978 expression in the peritoneal metastasis cell line MKN45 decreased legumain protein expression and chemosensitized the cells to treatment with docetaxel. However, replenishment of one and concomitant depletion of the other failed to induce chemosensitivity to docetaxel. Replenishment of miR-3978 also resulted in induction of PCBP1 protein expression, potentially indicating that miR-3978 expression might downregulate a negative regulator targeting PCBP1. Our current study reveals PCBP1 as an additional biomarker in peritoneal metastasis. PCBP1 and miR-3978 expression were correlated and suggests a potential interplay of differential miRNA biogenesis and RNA binding protein during metastatic progression.</jats:p
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
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