1,721,160 research outputs found
Design of Peptide Inhibitors of the Human Chaperone Protein Hsp70
Hsp70 is a protein that refolds misfolded proteins and has housekeeping functions which regulate apoptosis and other cellular activities. Hsp70 consists of a nucleotide-binding domain which binds ATP and a substrate binding domain that binds misfolded proteins. The substrate-binding domain contains a peptide-binding pocket which is covered by an a-helical lid that consists of helices A-E and a tail. The movement of the lid is important for the biological activity of Hsp70.|In cancer cells, the Hsp70-1 isotype helps to inhibit apoptosis in response to stress and treatment with drugs. The depletion or inhibition of Hsp70-1 results in the apoptosis of only cancerous cells. This makes Hsp70-1 a good target for the inhibition of cancer growth. |The design of peptides that specifically bind to the lid of human Hsp70-1 and restrict the movement of the lid, would make good Hsp70-1 specific inhibitors. To this end peptides were designed through the modification of the structure of Pyr, an antimicrobial peptide that binds to the lid of DnaK and the screening of a combinatorial peptide library. Ten Pyr(1-10)-NH2 analogs and a combinatorial library of 274,360 tri- and tetra-peptides were docked to the lid of the SBD of Hsp70-1 using Glide and Molegro molecular docking software, respectively. The MD simulations of the Pyr(1-10)-NH2 analog – Hsp70-1 complexes showed that Pyr(1-10)-NH2 and [Ala3]Pyr(1-10)-NH2 bound to the lid of Hsp70-1, were able to stabilize the structure of the lid and restrict lid movement. When these analogs were synthesized they had a significant inhibitory effect on the ATPase activity of Hsp70-1, but not Hsp70-8. The docking of the combinatorial libraries to the lid of Hsp70-1 and the MD simulations of the peptide – Hsp70-1 complexes identified peptides that formed a stable complex with the lid and restricted lid movement. Of these peptides, Arg-Glu-Val was shown to inhibit the ATPase activity of Hsp70-8 in addition to Hsp70-1, indicating it was not Hsp70-1 specific.|The peptides that the docking calculations predicted would bind to the lid of Hsp70-1 and restrict lid movement in the MD simulations, were shown experimentally to inhibit the ATPase activity of Hsp70-1. This work has laid a foundation for the further development and refinement of Hsp70-1 inhibitors through the computational screening of peptides.ProQuest Traditional Publishing Optionxxviii, 199 page
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
We 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
We 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.
Author-wise bibliometric analysis based on entropy.</p
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