Activity

Computer-aided drug design techniques are today largely applied in medicinal chemistry. In particular, receptor-based virtual screening (VS) studies, in which molecular docking represents the gold standard in silico approach, constitute a powerful strategy for identifying novel hit compounds active against the desired target receptor. Nevertheless, the need for improving the ability of docking in discriminating true active ligands from inactive compounds, thus boosting VS hit rates, is still pressing. In this context, the use of binding free energy evaluation approaches can represent a profitable tool for rescoring ligand-protein complexes predicted by docking based on more reliable estimations of ligand-protein binding affinities than those obtained with simple scoring functions. In the present review, we focused our attention on the Molecular Mechanics-Poisson Boltzman Surface Area (MM-PBSA) method for the calculation of binding free energies and its application in VS studies. We provided examples of successful applications of this method in VS campaigns and evaluation studies in which the reliability of this approach has been assessed, thus providing useful guidelines for employing this approach in VS.A high-quality dielectric layer is essential for organic thin-film transistors (OTFTs) operated at a low-power consumption level. In this study, a facile improved technique for the synthesis of solution-processed silica is proposed. By optimizing the synthesis and processing technique fewer pores were found on the surface of the film, particularly no large holes were observable after improving the annealing process, and the improved solution-gelation (sol-gel) SiOx dielectric achieved a higher breakdown strength (1.6 MV/cm) and lower leakage current density (10-8 A/cm2 at 1.5 MV/cm). Consequently, a pentacene based OTFT with a high field effect mobility (~1.8 cm2/Vs), a low threshold voltage (-1.7 V), a steeper subthreshold slope (~0.4 V/dec) and a relatively high on/off ratio (~105) was fabricated by applying a hybrid gate insulator which consisted of improved sol-gel SiOx and polyvinyl phenol (PVP). This could be ascribed to both the high k of SiOx and the smoother, hydrophobic dielectric surface with low trap density, which was proved by atomic force microscopy (AFM) and a water contact angle test, respectively. Additionally, we systematically studied and evaluated the stability of devices in the compressed state. The devices based on dielectric fabricated by conventional sol-gel processes were more susceptible to the curvature. While the improved device presented an excellent mechanic strength, it could still function at the higher bending compression without a significant degradation in performance. Thus, this solution-process technology provides an effective approach to fabricate high-quality dielectric and offers great potential for low-cost, fast and portable organic electronic applications.Deadly pathogens and parasites are transmitted by vectors and the mosquito is considered the most threatening vector in public health, transmitting these pathogens to humans and animals. We are currently witnessing the emergence/resurgence in new regions/populations of the most important mosquito-borne diseases, such as arboviruses and malaria. This resurgence may be the consequence of numerous complex parameters, but the major cause remains the mismanagement of insecticide use and the emergence of resistance. Biological control programmes have rendered promising results but several highly effective techniques, such as genetic manipulation, remain insufficiently considered as a control mechanism. Currently, new strategies based on attractive toxic sugar baits and new agents, such as Wolbachia and Asaia, are being intensively studied for potential use as alternatives to chemicals. Research into new insecticides, Insect Growth Regulators, and repellent compounds is pressing, and the improvement of biological strategies may provide key solutions to prevent outbreaks, decrease the danger to at-risk populations, and mitigate resistance.This study assesses the potential human health risks posed by six heavy metals (Hg, As, Pb, Cd, Cu, and Zn) found in five of the most consumed fish species (Mugil incilis, Centropomus undecimalis, Cathorops mapale, Eugerres plumieri, and Elops smithi) collected by the riverine population living in Ciénaga Grande de Santa Marta (CGSM), the largest estuary in Colombia. Metal concentrations were low compared with those reported in other regions around the world and the maximum value established by international monitoring organizations. The estimation of the potential risk (HQ) indicated that Cu and Hg could generate negative effects in groups of women of childbearing age (WCA) and the remaining population (RP), because they exceeded their related reference doses, with HQ values > 1; however, Cu and Hg concentrations were not high in fish and EWI, MFW, or MeHgPSL values shows that there is no evidence of a potential health risk from MeHg exposure in the study population. Therefore, the recommendations are to establish continuous monitoring of heavy metals together with strategies that address the high fish consumption, as well as to implement mechanisms for the mitigation of contamination of the watershed, to ensure the safety of organisms in the ecosystem and human health, not only of populations who depend on aquatic resources in the area but also of those that market and consume these resources in the Colombian Caribbean.The study evaluated incidences and potential differences of traumatic and nontraumatic fatalities among recreational skiers and snowboarders on Austrian ski slopes within a 10-year analysis. Within this retrospective study, data were collected by the Federal Ministry of the Interior. Data comprised all traumatic and nontraumatic deaths on Austrian ski slopes which occurred between the 2008/09 and 2017/18 winter seasons. Age, sex, nationality, gear used, altitude, slope difficulty, accident cause, primary cause of death and helmet use were collected at the death scene. Selleckchem 3-AP Incidence of fatalities was calculated based on number of skier days. In total, 369 fatalities, with an average of 36.9 ± 7.9 fatalities per year, were registered. The yearly incidence of traumatic and nontraumatic deaths decreased by 25.8% and 40.1% during the 10-year time period, leading to an evaluated mean incidence of 0.70 deaths per million skier days, with an incidence of 0.36 traumatic deaths and 0.34 nontraumatic deaths per million skier days.