1,721,003 research outputs found
Functional 3-Arylisoxazoles and 3-Aryl-2-isoxazolines from reaction of aryl nitrile oxides and enolates: Synthesis and reactivity
No full textHeterocyclic compounds are crucial starting reagents and intermediates, or they are direct precursors of target chemicals and/or bio-pharmacological active compounds. Today, they are used in the total synthesis of natural products, in drugs or herbicides, and agrochemical preparation. Developing synthetic strategies targeting isoxazoles is a recurrent aim in preparative chemistry. In particular, five-membered heterocycles such as isoxazoles and isoxazolines are easily formed in a two steps or by a 'one-pot' procedure, by reacting aryl nitrile oxides with a variety of enolates of carbonyl compounds (i.e., aldehydes, ketones, carboxylic acids), followed by aromatization. Such a methodology was found to be selective and versatile allowing the preparation of pharmacologically active isoxazoles in high yields. 1 Introduction 2 Preparation, Synthetic Applications, and Reactivity of 3-Aryl-5-hydroxy-2- isoxazolines and 3-Arylisoxazoles 3 Synthesis of 5-Alkyl-3-aryl-5-hydroxy-2- isoxazolines and 5-Alkyl-3-arylisoxazoles 4 Synthesis and Reactivity of 3,4-Diaryl-5-hydroxy-2-isoxsazolines and 3,4-Diarylisoxazoles 5 Synthesis and Reactivity of 3-Aryl-5-hydroxy-5-vinyl-2-isoxazolines and 3-Aryl-5- vinylisoxazoles 6 Synthesis of 3-Aryl-4-phenylisoxazole-5-carboxylic Acid 7 Conclusions 8 Experimental Methodologies. © Georg Thieme Verlag Stuttgart
A Simplified Direct O2 Consumption-Based Assay to Test COX Inhibition
No full textBackground: Cyclooxygenase is a well-known oxidoreductase that catalyzes the uptake of two moles of O2 by arachidonic acid (AA), producing the hydroperoxide Prostaglandin G2 (PGG2), then reduced to the prostaglandin precursor Prostaglandin H2 (PGH2). O2 consumption during such reactions is a measure of cyclooxygenase activity. O2 involved is generally measured by indirect methods, accomplished in the presence of the substrate AA and/or inhibitors. Methods: We developed a new simplified and easy to be carried out protocol for O2 consumption measurement by using disrupted HEK293-derived adherent cells, stably transfected either with COX-1 or COX-2 genes, as a source of the COX enzymes. The Clark electrode is used to measure the O2 concentration variation during the enzyme-catalyzed reactions. Results and Discussion: The novel assay was validated by determining the IC50 values of the known inhibitors such as indomethacin, ibuprofen, SC560, and celecoxib. Indomethacin and ibuprofen are two traditional non-steroidal anti-inflammatory drugs (tNSAIDs). SC560 is a commercially available reference compound used for COX-1 inhibition investigations. Celecoxib is a clinically used COXIBs. The assay was also applied to measure the kinetics and IC50 of mofezolac and P6. Mofezolac is the most potent selective COX-1 inhibitor, and active principle ingredient of Disopain® used to treat rheumatoid arthritis in Japan. P6, uncovered by us, is used together with mofezolac as a reference in in vitro and in vivo COX inhibition investigations and as a scaffold for structure-inhibition activity relationship studies. Conclusion: The obtained results showed the suitability of the newly developed assay to measure COXs activity in the presence of inhibitors as well as the kinetics of the inhibition (i.e., Vmax and Km)
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
COX-1 INHIBITORS AS ANTI-PLATELET AGENTS IN COVID-19
No full textCoronavirus Disease 19 (COVID-19) is primarily a lung disease which frequently leads to major cardiovascular complications and a poor prognosis due to excessive platelet activation, uncontrolled immune/inflammatory reactions ("cytokine storm"), endothelial dysfunction, and coagulopathy.1 Aspirin, due to its anti-inflammatory and anti-platelet aggregation properties, has been evaluated as a potential therapeutic agent for COVID-19. Low-doses Aspirin (typically 75–81 mg/day) irreversibly inhibits platelet cyclooxygenase-1 (COX-1) by Ser530 acetylation preventing conversion of arachidonic
acid into PGG2/PGH2, the latter in turn transformed by thromboxane synthase in thromboxane A2, thus resulting in an antithrombotic effect. Unfortunately, its use is limited by gastrointestinal side effects and aspirin resistance.2 Therefore, novel COX-1 inhibitors are needed. Mofezolac (Figure) is the most potent and selective COX-1 inhibitor administrated to humans as an anti-arthritis drug (DisopainTM). It belongs to the diarylisoxazoles chemical class and used as a “hit compound” for Structure Activity
Relationship (SAR) studies to design novel leads with antithrombotic activity. Replacing one or both mofezolac methoxyl with chemical groups with either increasing steric hindrance and capable to establish different interactions inside the COX-1 active site allowed the identification of novel COX-1 inhibitors. Evaluation of their effects on the blood coagulation cascade is ongoing
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
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