1,721,018 research outputs found
STRUCTURAL INSIGHTS INTO INHIBITOR OF APOPTOSIS PROTEINS RECOGNITION BY PRO-APOPTOTIC COMPOUNDS
Get PDFInhibitor of Apoptosis Proteins (IAPs) are negative regulators of apoptosis and their overexpression is observed in many cancer cells, correlating with the inhibition of caspases. IAPs inhibitory function is exploited by the BIR domains, which were firstly identified in baculovirus. Among the IAP family, XIAP (X chromosome-linked IAP) directly inhibits caspases preventing proteolytic cleavage through its BIR2 and BIR3 domains; furthermore, XIAP-BIR1 in a dimeric form recognizes TAB1, a kinase activator, regulating pro-survival pathways. In the last years, cIAPs have become crucial players of the extrinsic pathway; in fact, through the recognition of TRAFs (TNF Receptor Associated Factors) by the cIAP2-BIR1 domain, they are recruited to the TNF- Receptor Signaling Complex and act as E3 ubiquitin ligases. One of the most promising approaches that have been proposed to inhibit these proteins is represented by the structure-based design of small molecules, named Smac-mimetics, that mimic Smac/DIABLO (Second mitochondria-derived activator of caspases/Direct IAp Binding protein with Low pI), an endogenous antagonist of IAPs. Initially designed in 2001 against the BIR3 domain of XIAP, Smac-mimetics have shown to prevent the inhibitory action of XIAP on initiator and executioner caspases, but also to bind to the BIR3 of cIAPs, inducing their autoubiquitylation and degradation. This work focuses on the cloning, expression and purification of the IAPs constructs of interest and their biochemical and biophysical characterization alone and in the presence of some of the Smac-mimetics from our library. The X-ray technique on crystals and protein solutions allowed a structural study of the protein-ligand complexes at atomic level, favoring the process of drug lead optimization. Furthermore, the screening of libraries of pharmacologically active compounds through in silico docking searches on new targets, such as XIAP- and cIAP2-BIR1, resulted in the discovery of potential new pro-apoptotic leads, whose clinical properties are known. Since in the last months new macromolecular protein complexes have been identified as involved in apoptosis and pro-survival pathways, novel protocols for the expression and purification of cIAP1 and TRAFs full length constructs have been optimized to obtain pure and homogeneous samples ready for the structural characterization
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
