The quest for broad-spectrum coronavirus inhibitors

The potential for zoonotic transmission and global spread demonstrated by the pandemic SARS-CoV-2, and its burden on public health, have emphasized the critical need to develop highly efficacious strategies for prophylaxis and therapy of infections with coronavirus at large. This thesis was largely dedicated to the search of coronavirus inhibitors by phenotypic cell-based screenings using different classes of compounds including immunosuppressive and non-immunosuppressive derivatives of cyclosporin A, hits from FDA-approved drug libraries and molecules synthesized by collaborators. Although, no effective therapies were found, this work warranted the further clinical investigation of a non-immunosuppressive compound in SARS-CoV-2-infected kidney transplant recipients, which is currently in progress. The development of antiviral therapies requires a detailed understanding of CoV replication and its interplay with host cells. Here, an in-depth characterization of the viral replicase subunit non-structural protein 14 provides evidence for its importance for virus viability and fitness, while establishing that nsp14 might be a good target for drug design with a potential pan-coronaviral activity spectrum. In the discussion, the history of unsuccessful CoV-targeting antivirals is briefly summarized, together with possible new approaches in antiviral research. Lastly, some prospects for future research are outlined. </p

Dispersion of multi-walled carbon nanotubes in [BMIM]PF 6 for electrochemical sensing of acetaminophen

The influence of functionalized multi-walled carbon nanotubes (fMWCNT) in the presence of 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM]PF6) in different ratios was investigated on the acetaminophen (ACOP) electrochemical determination. The electrochemical behavior of the ACOP exhibited a pair of well-defined redox peaks, suggesting that the reversibility of ACOP was significantly improved in comparison to irreversible oxidation peak on bare GCE. The redox process was controlled by adsorption, involves two electrons and the value of apparent rate constant (ks) was equal to 14.7 s-1 ± 3.6 s-1. The analytical curves were obtained for concentrations of ACOP ranging from 0.3 to 3.0 μmol L-1. The values of the detection limit were calculated from SWV and found to be 6.73 × 10-8 mol L-1. The proposed electrochemical sensor exhibited good stability and reproducibility and was applied for ACOP determination in tablets (Tylenol® and Tylenol®DC) with satisfactory results.The authors gratefully acknowledge funding provided by the following Brazilian agencies: CNPq-INCT (Proc. 573925/2008-9 and 573548/2008-0), CAPES/Funcap (2133/2012/Proc. 23038.007973/2012-90), CNPq-PVE (Proc. 400223/2014-7 and 303596/2014-7), PRONEX/FUNCAP (Proc. PR2-0101-00030.01.00/15) and CNPq (Proc. 302801/2014-6). R.N. Gomes thanks CAPES and C.P. Sousa thanks CAPES-PNPD for their grants. The authors also are grateful to the Central Analítica-UFC/CT-INFRA/MCTI-SISNANO/Pró-Equipamentos CAPES for technical support and Prof. Pierre Basílio Almeida Fechine and MsC. Davino Machado Andrade Neto for Zeta potential analysis.info:eu-repo/semantics/publishedVersio

Relative Growth Of Carcass Tissues Of Goat Kids From Five Breed Types Finished On Pasture Or Feedlot

The aim of this study was to evaluate the effect of cross breeding, finishing system, and gender on the relative growth of carcass tissues of dairy kids. Seventy eight kids (39 male and 39 female) from five breed types were used: Alpine; 1/2 Boer + 1/2 Alpine (1/2 BA); 1/2 Nubian + 1/2 Alpine (1/2 ANA); 3/4 Boer + 1/4 Alpine (3/4 BA); and 1/2 Nubian + 1/4 Boer + 1/4 Alpine (TC). Kids were distributed into two finishing systems: in pasture with doe (FS1) and weaned in feedlot (FS2). Kids were slaughtered at a mean age of 128.4 ± 7.9 days and mean live weight of 22.07 kg. The mean weight of half carcasses was 5.09 kg. To determine allometric growth, we used the exponential equation Y= aXb. In the half carcass, muscle tissue showed comparatively early growth in group 1/2 BA, whereas fat tissue of animals in FS1 had relatively late growth. Females exhibited early growth of muscle tissue, while in males this tissue was intermediate. The 1/2 BA first-cross improved carcass characteristics by enhancing the growth of muscle tissue.37298999

Transport in Coupled Quantum Dots: Kondo Effect Versus Anti-Ferromagnetic Correlation

The interplay between the Kondo effect and the inter-dot magnetic interaction in a coupled-dot system is studied. An exact result for the transport properties at zero temperature is obtained by diagonalizing a cluster, composed by the double-dot and its vicinity, which is connected to leads. It is shown that the system goes continuously from the Kondo regime to an anti-ferromagnetic state as the inter-dot interaction is increased. The conductance, the charge at the dots and the spin-spin correlation are obtained as a function of the gate potential.Comment: 4 pages, 3 postscript figures. Submitted to PR

Chemoenzymatic synthesis of (S)-Pindolol using lipases

A straightforward chemoenzymatic synthesis of (S)-Pindolol has been developed. The key step involved the enzymatic kinetic resolution of rac-2-acetoxy-1-(1H-indol-4-yloxy)-3-chloropropane with lipase from Pseudomonas fluorescens via hydrolytic process to obtain enantiomerically enriched halohydrin (2S)-1-(1H-indol-4-yloxy)-3-chloro-2-propanol (96% ee) and (2R)-2-acetoxy-1-(1H-indol-4-yloxy)-3-chloropropane (97% ee). The latter was subjected to a hydrolysis reaction catalyzed by Candida rugosa leading to (2R)-1-(1H-indol-4-yloxy)-3-chloro-2-propanol (97% ee), followed by a reaction with isopropylamine, producing (S)-Pindolol (97% ee) in quantitative yield

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In the last years many populations of anurans have declined and extinctions have been recorded. They were related to environmental pollution, changes of land use and emerging diseases. The main objective of this study was to determine copper sensitivity of the anuran of the Amazon Rhinella granulosa and Scinax ruber tadpoles at stage 25 and Scinax ruber eggs exposed for 96 h to copper concentrations ranging from 15 µg Cu L-1 to 94 µg Cu L-1. LC50 at 96 h of Rhinella granulosa Gosner 25, Scinax ruber Gosner 25 and Scinax ruber eggs in black water of the Amazon were 23.48, 36.37 and 50.02 µg Cu L-1, respectively. The Biotic Ligand Model was used to predict the LC50 values for these species and it can be considered a promising tool for these tropical species and water conditions. Copper toxicity depends on water physical-chemical composition and on the larval stage of the tadpoles. The Gosner stage 19-21 (related to the appearance of external gills) is the most vulnerable and the egg stage is the most resistant. In case of contamination by copper, the natural streams must have special attention, since copper is more bioavailable.Nos últimos anos foram registrados muitas extinções e declínios de populações de anuros. Eles estavam relacionados com a poluição do ambiente, a mudanças no uso da terra e ao surgimento de doenças. O principal objetivo deste estudo foi determinar a sensibilidade dos anuros amazônicos ao cobre. Os girinos de Scinax ruber e Rhinella granulosa no estadio 25 e os ovos de Scinax ruber foram expostos por 96 horas a concentrações de cobre entre 15 µg Cu L-1 a 94 µg Cu L-1. A CL50 -96 h dos girinos de Rhinella granulosa, dos girinos de Scinax ruber e dos ovos de Scinax ruber em águas pretas da Amazônia foram 23,48; 36,37 e 50,02 µg Cu L-1, respectivamente. O modelo do ligante biótico foi usado para prever os valores de CL50 para essas duas espécies e pode ser considerado uma ferramenta promissora para essas espécies tropicais e para essas condições de água. A Toxicidade de cobre depende da composição físico-química da água e do estagio larval dos girinos. O estadio 19-21 de Gosner (relacionados ao aparecimento das brânquias externas) são os mais vulnerável e o estagio de ovo é o mais resistente. Em caso de contaminação por cobre, os igarapés naturais devem ter uma atenção especial, uma vez que o cobre é mais biodisponível nesse ambiente

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio