1,720,988 research outputs found
Ligand based virtual screening studies to design drug molecules for human PIN1 causing cardiovascular disease
Full text linkPIN1 is a member of the cis/trans peptidyl-prolyl isomerase family which plays critical roles in cell-cycle regulation. Over expression of PIN1 in endothelial cells causes cardiovascular disease. The present study has focused on computational analysis to identify the potential inhibitors for PIN1. The human PIN1 crystal structure was retrieved from the protein data bank and prepared using protein preparation wizard of Maestro v9.2. Fourteen PIN1 inhibitors reported in recent literature were acquired and searched for structural analogs using Ligand.Info tool. 5675 PIN1 inhibitor analogs yielded were converted to 3D structures using LigPrep with constraints of ADME evaluation and toxicity assessments. The 3D ligand dataset was docked to PIN1 through docking protocol of Glide v5.7. Nine leads showing better binding affinity compared to fourteen published inhibitors were proposed as potential inhibitors of PIN1. The Lead 1 (2-(2-hydroxy-5-methoxy-pheny)-1h-benzoimidazole-5-carboxamidine) showed a docking score of -7.543 kcal/mol with strong hydrogen bond network with active site residues such as Arg-74, Tyr-92 and Glu-110 and good van der Waals interaction. Therefore, Lead 1 is proposed as a promising lead for developing potential drug molecules for cardiovascular disease therapy
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
Envelope protein as molecular target for YFV (Yellow fever virus) drug discovery
Full text linkYellow fever (YF), a mosquito-borne viral haemorrhagic fever, is one of the most lethal viral diseases. Despite the availability of vaccines, yellow fever virus (YFV) strikes an estimated 2, 00,000 persons world-wide each year and causes 30,000 deaths approximately. There are no approved antiviral therapies for the treatment of YFV disease in humans. YFV 17D strain RNA genome is of 10,862 nucleotides, which encodes three structural proteins (C, PrM, and E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5). Identification of different protein functions facilitates a mechanistic understanding of YFV infection and opens novel means for drug development. Functional assignment of complete YFV proteome was done through support Vector machine (SVM). Significant functions of YFV Envelope (E) protein are Transmembrane, Aptamer-binding protein, Coat protein, Zinc-binding, Manganese-binding and Metal-binding etc. The E protein being non homologous to human and important in receptor binding, hemagglutination of erythrocytes at acidic pH, induction of the protective immune response, and involvement in an intraendosomal acid-catalyzed fusion step necessary for infection was selected as a potent molecular target against YFV drug discovery. 3D structure of target protein E protein is predicted using MODELLER9V6 and validated through PROCHECK analysis. The Binding site tool of Discovery Studio 2.0 was used to find sites all over protein. Heparin was identified as an important ligand against the molecular target and was docked to the functionally important binding site using LigandFit protocol. The YFV E protein -Heparin docking complex associated with strong hydrogen bonding with SER 483, GLN 443 and ALA 441 residues. The strong docking interaction may impede the infection causes due to association of YFV E protein and Core membrane. Further, the predicted model can be used as reference towards designing candidate drugs against YFV
Docking studies to explore novel lead molecules for human Spleen tyrosine kinase involved in chronic lymphocytic leukemia
Full text linkB-cell chronic lymphocytic leukemia (CLL) is the most prevalent B-cell malignancy in adults. Despite advances in treatment, the disease remains incurable, warranting further efforts to identify novel molecular targets and inhibitors. Spleen tyrosine kinase (SYK) plays a pivotal role for B-lymphocyte development and maturation in the B-cell receptor (BCR) signaling pathway and hence represents a potential therapeutic target for CLL. The present study is directed towards finding novel inhibitors of SYK through ligand based virtual screening. The co-crystal structure of SYK was investigated to locate active site residues (Glu-449, Ala-451 Arg-498, Asn-499, Ser-511, and Asp-512). Five SYK specific published inhibitors (Gleevec, staurosporine, Bay61-3606, R-406 and p5c) were explored against more than one million entries of the Ligand.Info metadatabase to create an in-house library of 1957 structural analogs. Ligand dataset was prepared using LigPrep and filtered based on Lipinski’s rule of five and reactive group constraints. Docking using Computational Glide v5.5 from lesser to higher stringency towards minor steric classes were applied subsequently to the prepared ligand dataset against a grid around the centroid of the SYK active site. Fifteen lead molecules with good binding affinity to SYK were identified and compared with binding affinities and orientations of five published inhibitors. Apigenin (-10.05 Kcal/mol) and Glafenine (-9.72 Kcal/mol) endeavored better binding affinities, hydrogen bonding network and Van der Waal interactions with active site residues compared to published inhibitors. Thus, Apigenin and Glafenine would be valuable for designing a novel inhibitor against CLL, if synthesized and tested in vitro and in vivo
- …
