1,720,974 research outputs found
Efficient inhibition of HIV-1 aspartic protease by synthetic, computer designed peptide mimetics
No full textInhibitors of HIV-1 aspartic protease, an enzyme which is essential for viral processing and maturation, represent an important new type of anti-AIDS drug. To be effective, these must be potent and selec tive, must present a suitable pharmacological profile with respect to drug uptake and clearance, and should also be synthesizeable in good yields. We have developed a design method based on computer aided modification of a reference compound for which the crystal structure of the complex with the enzyme is known. After relaxation of the new structures to an optimized geometry, the complexation energy is calculated, relative to that of the reference inhibitor, taking into account all aspects of the interaction, including solvation. This affords a numerical prediction of the putative effectiveness of the new structure as an inhibitor, relative to that of the reference structure, and thus allows us to rapidly evaluate modifications that could result in increased potency and reduce the number of compounds that it is actually necessary to synthesize so as to obtain useful lead compounds for drug development. In an initial study, we have determined the role of flanking residues in modulating inhibition, for hexapeptide mimetics with a central, reduced amide non-cleavable bond. The structure was based on that of the reference inhibitor MVT-101. We have found that by tuning the residues flanking the central bond, the complexation energy could be markedly improved, and have determined that the putatively optimal structure should contain an aromatic residue (Phe or Tyr) at positions p1 and p1', immediately flanking the central bond, a hydrophobic residue at P2, a glutamic acid residue at P2', and an aromatic residue (Phe, Tyr or Trp) at positions P3 and P3', most distant from the central bond. Synthesis of a series of inhibitors containing these modifications was carried out entirely in the solid phase, using Fmoc type chemistry, on a polyethylene glycol/polystyrene resin, and in vitro enzyme inhibition assays have confirmed the computer-based predictions. In particular, it was possible to obtain several inhibitors with potency in the low nanomolar range, an improvement of several orders of magnitude with respect to the parent compound
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
A Plant-Defensin from Sugarcane (Saccharum spp.)
No full textComparing available Poaceae defensins with sugarcane ESTs, a putative defensin gene was identified in sugarcane and cloned from genomic sugarcane DNA. The deduced encoded peptide shows the structure and amino acid composition typical of other plant defensins. Using RT-PCR, defensin expression in sugarcane and differences between "normal" and infected sugarcane were evidenced
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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