1,720,960 research outputs found
α4β1 integrin targeting ligands for selective antineoplastic drug delivery in cancer cells
No full textEvaluation of New β -Lactam Derivatives’ Effects on α4β1 and αMβ2 Leukocyte Integrin-Mediated Immune Cells Activation and Migration
No full textTargeting α4β1 integrin: from cyclic to linear ligands, effects of chemical modifications
No full textThe immune system depends on integrins for adhesion and migration during leukocyte trafficking and for intracellular signalling. There is a causal relationship between dysregulation of integrin expression and the onset of pathological conditions, such as autoimmune diseases, inflammation, cancer, and infections. Therefore, integrins, such as α4β1, are considered important therapeutic targets. In this study, a series of novel compounds were synthesized and evaluated for affinity and potency towards α4β1, and selectivity towards α5β1, and αMβ2 integrins. Three compounds 3, 4, and 8 showed excellent binding affinities (Ki < 10 nM) for α4β1. In cell adhesion assays these three ligands behaved as antagonists of α4β1, as confirmed by integrin-mediated intracellular signalling with a functional selectivity over ERK1/2 signalling pathway. Notably, compound 4, a proline derivative, was an antagonist against α4β1 (IC50 15 ± 3 nM) and an agonist against αMβ2 integrin (EC50 23 ± 5 nM). Compound 2, a fluorinated β-lactam derivative, was a selective and potent agonist of α5β1 (EC50 45.98 ± 7.92 nM). Compound 5, although it seems to bind to a different site compared to LDV in α4β1 integrin, showed an agonist behaviour in cell adhesion mediated by α4β1 and α5β1 integrin (EC50 25 ± 3 and 4.8 ± 3.4 nM, respectively) and in activating α4β1 integrin-mediated ERK1/2 and Akt phosphorylation. Compound 8 was the most potent agonist of the series against αMβ2 (EC50 1.4 ± 0.2 nM). Overall, the present study provides new insights into the effects of new integrin ligands that could be considered as potential lead compounds for therapeutic applications in inflammatory diseases and cancer
Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams
Full text linkThe direct nucleophilic addition of amides to unfunctionalized alkenes via photoredox catalysis represents a facile approach towards functionalized alkylamides. Unfortunately, the scarce nucleophilicity of amides and competitive side reactions limit the utility of this approach. Herein, we report an intramolecular photoredox cyclization of alkenes with β-lactams in the presence of an acridinium photocatalyst. The approach uses an intramolecular nucleophilic addition of the β-lactam nitrogen atom to the radical cation photogenerated in the linked alkene moiety, followed by hydrogen transfer from the hydrogen atom transfer (HAT) catalyst. This process was used to successfully prepare 2-alkylated clavam derivatives
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
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