SARS-CoV-2 infection: The role of cytokines in COVID-19 disease.

COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19

Fast quadtree level decision algorithm for H.264/HEVC transcoder

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On the use of local search heuristics to improve GES-based Bayesian network learning

Bayesian networks learning is computationally expensive even in the case of sacrificing the optimality of the result. Many methods aim at obtaining quality solutions in affordable times. Most of them are based on local search algorithms, as they allow evaluating candidate networks in a very efficient way, and can be further improved by us ing local search-based metaheuristics to avoid getting stuck in local optima. This approach has been successfully applied in searching for network structures in the space of directed acyclic graphs. Other algorithms search for the networks in the space of equiva lence classes. The most important of these is GES (Greedy Equiv alence Search). It guarantees obtaining the optimal network under certain conditions. However, it can also get stuck in local optima when learning from datasets with limited size. This article proposes the use of local search-based metaheuristics as a way to improve the behaviour of GES in such circumstances. These methods also guar antee asymptotical optimality, and the experiments show that they improve upon the score of the networks obtained with GES

El jardín botánico y la botánica farmacéutica en la Habana del siglo XIX

El Jardín Botánico de La Habana, fundado en 1817, fue una institución diseñada en sus comienzos como un centro de estudio, clasificación y análisis de las plantas existentes en la isla, mediante la aplicación de los conocimientos adquiridos a la rentabilización de los cultivos. Poco a poco, se iría configurando como una entidad vinculada al mundo científico, consolidándose el estudio de la Botánica, indispensable para la Farmacia. La alianza Botánica y Farmacia tuvo su máxima relación en el Jardín durante la dirección del mismo por Pedro Alejandro Auber, valedor de la Botánica Farmacéutica, e interesado en la realización de una flora cubana. Posteriormente, el Jardín sería dirigido por diversas instituciones hasta llegar a la Universidad, en la cual la Botánica formaría parte del estudio en diversas facultades, entre ellas la de Farmacia, convirtiéndose en una materia clave en la formación de los farmacéuticos. El objetivo de nuestro trabajo es profundizar en la Botánica en la isla durante el siglo XIX, analizando su relación con la Farmacia y utilizando como hilo conductor la trayectoria histórica del Jardín Botánico de La Habana. Pretendemos concretar la información médico farmacéutica sobre la Botánica en la isla y establecer cronológicamente cómo se va configurando su estudio en base a fuentes bibliográficas y archivísticas.The Botanical Garden of Havana, founded in 1817, was an institution designed at the beginning as a centre for the study, classification and analysis of existing plants on the island, using the acquired knowledge to improve crop profitability. Progressively, it would take shape as an institution linked to the scientific world, where the study of Botany, essential in many fields of study such as that of Pharmacy, would be established. The Garden underwent its closest bond with Pharmacy under the direction of Pedro Alejandro Auber, which would lend special importance to Botany from a pharmaceutical point of view, focusing on the creation of a Cuban Flora. Subsequently, the Garden would be directed by various institutions until it became part of the university, where Botany would be part of the curriculum in several schools, such as the School of Pharmacy, where it was a key subject in pharmaceutical education. The aim was to delve into the study of Botany during the nineteenth century emphasizing its closest link to Pharmacy, using the history of the Botanical Garden in Havana as a connecting thread. We try to gather more specific pharmaceutical and medical information about the island’s Botany and to establish a chronology of how the study of this matter evolves throughout the century using bibliographic and archive sources

A hybrid of 1-deoxynojirimycin and benzotriazole induces preferential inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE)

The synthesis of four heterodimers in which the copper(I)-catalysed azide-alkyne cycloaddition was employed to connect a 1-deoxynojirimycin moiety with a benzotriazole scaffold is reported. The heterodimers were investigated as inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). The heterodimers displayed preferential inhibition (> 9) of BuChE over AChE in the micromolar concentration range (IC50 = 7–50 µM). For the most potent inhibitor of BuChE, Cornish-Bowden plots were used, which demonstrated that it behaves as a mixed inhibitor. Modelling studies of the same inhibitor demonstrated that the benzotriazole and 1-deoxynojirimycin moiety is accommodated in the peripheral anionic site and catalytic anionic site, respectively, of AChE. The binding mode to BuChE was different as the benzotriazole moiety is accommodated in the catalytic anionic site.publishedVersio

A Comprehensive Evaluation of Sdox, a Promising H2S-Releasing Doxorubicin for the Treatment of Chemoresistant Tumors

Sdox is a hydrogen sulfide (H2S)-releasing doxorubicin effective in P-glycoprotein-overexpressing/doxorubicin-resistant tumor models and not cytotoxic, as the parental drug, in H9c2 cardiomyocytes. The aim of this study was the assessment of Sdox drug-like features and its absorption, distribution, metabolism, and excretion (ADME)/toxicity properties, by a multi- and transdisciplinary in silico, in vitro, and in vivo approach. Doxorubicin was used as the reference compound. The in silico profiling suggested that Sdox possesses higher lipophilicity and lower solubility compared to doxorubicin, and the off-targets prediction revealed relevant differences between Dox and Sdox towards several cancer targets, suggesting different toxicological profiles. In vitro data showed that Sdox is a substrate with lower affinity for P-glycoprotein, less hepatotoxic, and causes less oxidative damage than doxorubicin. Both anthracyclines inhibited CYP3A4, but not hERG currents. Unlike doxorubicin, the percentage of zebrafish live embryos at 72 hpf was not affected by Sdox treatment. In conclusion, these findings demonstrate that Sdox displays a more favorable drug-like ADME/toxicity profile than doxorubicin, different selectivity towards cancer targets, along with a greater preclinical efficacy in resistant tumors. Therefore, Sdox represents a prototype of innovative anthracyclines, worthy of further investigations in clinical settings

Future mmVLBI Research with ALMA: a European vision

Very long baseline interferometry at millimetre/submillimetre wavelengths (mmVLBI) offers the highest achievable spatial resolution at any wavelength in astronomy. The anticipated inclusion of ALMA as a phased array into a global VLBI network will bring unprecedented sensitivity and a transformational leap in capabilities for mmVLBI. Building on years of pioneering efforts in the US and Europe the ongoing ALMA Phasing Project (APP), a US-led international collaboration with MPIfR-led European contributions, is expected to deliver a beamformer and VLBI capability to ALMA by the end of 2014 (APP: Fish et al. 2013, arXiv:1309.3519). This report focuses on the future use of mmVLBI by the international users community from a European viewpoint. Firstly, it highlights the intense science interest in Europe in future mmVLBI observations as compiled from the responses to a general call to the European community for future research projects. A wide range of research is presented that includes, amongst others: - Imaging the event horizon of the black hole at the centre of the Galaxy - Testing the theory of General Relativity an/or searching for alternative theories - Studying the origin of AGN jets and jet formation - Cosmological evolution of galaxies and BHs, AGN feedback - Masers in the Milky Way (in stars and star-forming regions) - Extragalactic emission lines and astro-chemistry - Redshifted absorption lines in distant galaxies and study of the ISM and circumnuclear gas - Pulsars, neutron stars, X-ray binaries - Testing cosmology - Testing fundamental physical constant