1,720,956 research outputs found
New Pyrolle and Pyrazole based compounds active as anti-inflammatory and antimalarial drugs
Full text linkThis thesis addresses the urgent requirement for novel anti-inflammatory drugs and antimalarial interventions:
The beneficial effects of carbon monoxide (CO) gained much interest in research and offer new potential treatments of vascular- and inflammatory-related diseases. However, the medical application of this gas has been hampered by the complexity of the administration route. This problem has been overcome with the discovery of CO-releasing molecules (CORMs), which are an effective tool to deliver CO safely and precisely to the target locations. Particularly, metal-based CORMs are emerging for their striking anti- inflammatory properties that are amplified by the transition metal and are being progressively improved in view of novel future applications.
We developed novel dual-active metal-based CORMs with the potential to be used as therapeutic agents in tendon-derived diseases. Specifically, we designed and synthesized dicobalt(0)hexacarbonyl (DCH)-CORMs containing structural fragments of COX-2 selective inhibitors and tested them for the CO release kinetic (myoglobin release assay) and anti- inflammatory/cytoprotective effects on hydrogen peroxide-stimulated human primary- derived tenocytes by taking in account the PGE2 secretion as a readout.
Malaria drug research and development efforts have recently resurged in the last decade following deceleration rate of mortality and malaria cases in endemic regions. Inefficiency of malaria interventions are largely driven by the spreading resistance of the Plasmodium falciparum parasite to the current drug regimens and from the malaria vector – mosquito Anopheles – to insecticides. In response to the new eradication agenda, the development of drugs that act by breaking the malaria transmission cycle (transmission-blocking drugs) has been recognized as an important and additional target for intervention. These drugs take advantage of the susceptibility of Plasmodium population bottlenecks before transmission (gametocytes) and in the mosquito vector (gametes, zygotes, ookinetes, oocysts,
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sporozoites). In this context, we sought to address the urgent requirement for novel antimalarial interventions by developing and aiding future discovery of transmission- blocking drugs.
We designed and synthesized analogues of the pyrazole MMV1580843, recently discovered in a high-throughput screening as a potent and selective gametocytocidal compound. SAR studies of these compounds hold promise for improved chemical modifications to progress to a hit-to-lead campaign. Particularly, we found that the pyrazole core allows a variety of substitutions that maintain potent activity towards late-stage gametocytes along with favorable physicochemical and safety profiles.
In parallel, from a phenotypic screening of compounds belonging to an in-house library, we discovered new pyrazole- and pyrrole-based compounds endowed with selective activity towards ring and trophozoite stages in the P. falciparum asexual cycle and potential activity against sporogonic stages in mosquitoes. The transmission-blocking potential was assessed by performing topical exposure assays on females Anopheles Gambiae mosquitoes of selected hits and found compound 19 and 12 to significantly decrease the parasite development in the mosquito midgut
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
Transmission-Blocking Strategies for Malaria Eradication: Recent Advances in Small-Molecule Drug Development
No full textMalaria drug research and development efforts have resurged in the last decade following the decelerating rate of mortality and malaria cases in endemic regions. The inefficiency of malaria interventions is largely driven by the spreading resistance of the Plasmodium falciparum parasite to current drug regimens and that of the malaria vector, the Anopheles mosquito, to insecticides. In response to the new eradication agenda, drugs that act by breaking the malaria transmission cycle (transmission-blocking drugs), which has been recognized as an important and additional target for intervention, are being developed. These drugs take advantage of the susceptibility of Plasmodium during population bottlenecks before transmission (gametocytes) and in the mosquito vector (gametes, zygotes, ookinetes, oocysts, sporozoites). To date, compounds targeting stage V gametocytes predominate in the chemical library of transmission-blocking drugs, and some of them have entered clinical trials. The targeting of Plasmodium mosquito stages has recently renewed interest in the development of innovative malaria control tools, which hold promise for the application of compounds effective at these stages. In this review, we highlight the major achievements and provide an update on the research of transmission-blocking drugs, with a particular focus on their chemical scaffolds, antiplasmodial activity, and transmission-blocking potential
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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