1,720,967 research outputs found
Exploring the recognition pathway at the human A2A adenosine receptor of the endogenous agonist adenosine using supervised molecular dynamics simulations
No full textAdenosine is a naturally occurring purine nucleoside that exerts a variety of important biological functions through the activation of four G protein-coupled receptor (GPCR) isoforms, namely the A1, A2A, A2B and A3 adenosine receptors (ARs). Recently, the X-ray structure of adenosine-bound hA2A AR has been solved, thus providing precious structural details on receptor recognition and activation mechanisms. To date, however, little is still known about the possible recognition pathway the endogenous agonist might go through while approaching the hA2A AR from the extracellular environment. In the present work, we report the adenosine-hA2A AR recognition pathway through the analysis of a series of Supervised Molecular Dynamics (SuMD) trajectories. Interestingly, a possible energetically stable meta-binding site has been detected and characterized
Inspecting receptor-ligand interaction using molecular dynamics simulations: new insights from Adenosiland
No full textOne of the most challenging issues for the future of drug discovery is the capability to understand the GPCR–ligand recognition pathway with the aim to facilitate the development of drug candidates with more favorable phamacodynamic profiles.
Unfortunately, the recognition process between a ligand and its receptor is a very rare event to describe at the molecular level, and even with the recent GPU-based computing resources, it is necessary to carry out classical molecular dynamics (MD) experiments in a long microsecond time scale. In order to overcome this limiting factor, we have implemented an alternative MD approach, named supervised molecular dynamics (SuMD), that enables us to follow GPCR–ligand approaching process within a time scale reduced up to three orders of magnitude compared to classical MD [1]. SuMD enables the investigation of ligand–receptor binding events independently from the starting position, chemical structure of the ligand, and also from its receptor binding affinity (Fig. 1).
We selected as a key study the human A2A adenosine receptor (hA2AAR) that has been recently crystallized with different ligands, both agonists and antagonists, characterized by different receptor binding affinities. We are able to accurately completely explore the receptor–ligand event in a nanosecond time scale. This approach is also very useful to analyze both orthosteric and allosteric binding events broadening our perspectives in several scientific areas from molecular pharmacology to drug discovery
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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