1,720,983 research outputs found
Non-covalent immunoproteasome inhibitors: virtual screening and in vitro test on β1i /β5i subunits
No full textImmunoproteasome inhibition is a challenging strategy for the treatment of hematological malignancies, autoimmune and inflammatory diseases [1,2]. The search for non-covalent inhibitors of the immunoproteasome β1i/β5i catalytic subunits could be a new strategy to avoid the drawbacks of the known covalent inhibitors. Here, we report the biological evaluation of thirty-four compounds selected from commercial libraries. A virtual screening strategy including a dynamic pharmacophore modeling approach onto the β1i subunit and a pharmacophore/docking approach onto the β5i subunit aided the identification of these hits [3]. Compound 3 is the most active onto β1i subunit with Ki = 11.84±1.63 μM, compound 17 showed Ki = 12.50±0.77 μM onto β5i subunit. Compound 2 showed inhibitory activity on both subunits (Ki = 12.53±0.18 Ki = 31.95±0.81 onto β1i subunit and β5i subunit, respectively). The hit compounds identified represent an interesting starting point for further optimization
Exploring the new non-covalent immunoproteasome inhibitors of β1i /β5i subunits: Virtual screening and in vitro test
No full text
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
An overview of recent molecular dynamics applications as medicinal chemistry tools for the undruggable site challenge
Full text linkMolecular Dynamics (MD) has become increasingly popular due to the development of hardware and software solutions
and improvement in algorithms, that allowed researchers to scale up calculations in order to speed up them. MD
simulations are usually used to address protein folding issues or protein-ligand complex stability through energy profile
analysis over time. In recent years, the development of new tools able to deeply explore Potential Energy Surface (PES)
allowed researchers to focus on the dynamic nature of binding recognition process and binding-induced protein
conformational change. Moreover, modern approaches have demonstrated to be effective and reliable in calculating some
kinetic and thermodynamic parameters behind the host-guest recognition process. Starting from all of these
considerations, several efforts have been made in order to integrate MD within the virtual screening process in drug
discovery. Knowledge retrieved from MD can be, in fact, exploited as a starting point to build pharmacophores or docking
constraints in the early stage of the screening campaign as well as to define key features, in order to unravel hidden
binding modes and help the optimisation of the molecular structure of a lead compound. Based on these outcomes,
researchers are nowadays using MD as an invaluable tool to discover and target previously considered undruggable
binding sites, including protein-protein interactions and allosteric sites on protein surface. As a matter of fact, the use of
MD has been recognised as vital in the discovery of selective protein-protein interaction modulators. The use of a dynamic
overview on how the host-guest recognition occurs and of the relative conformational modifications induced, allow
researchers to optimise small molecules and small peptides capable to tightly interact within the cleft between the two
proteins.
In this review we point to present the most recent applications of MD as integrated tool to be used in the rational design
of small molecules or small peptides able to modulate undruggable targets, such as allosteric sites and protein-protein
interactions
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
- …
