In vitro activity of bedaquiline against rapidly growing nontuberculous mycobacteria

Bedaquiline (BDQ) has been proven to be effective in the treatment of multidrug-resistant tuberculosis. We hypothesized that BDQ could be a potential agent to treat nontuberculous mycobacterial (NTM) infection. The objective of this study was to evaluate the in vitro activity of BDQ against rapidly growing mycobacteria by assessing the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against 18 NTM strains. For MIC determination we performed the resazurin microtitre assay broth dilution, and for the MBC the c.f.u. was determined. BDQ exhibited a strong inhibitory effect against most NTM tested; however, for some NTM strains the MBC was significantly higher than the MIC. A new finding is that Mycobacterium flavescens has a mutation in the gene atpE associated with natural resistance to BDQ. These preliminary promising results demonstrate that BDQ could be potentially useful for the treatment of NTM

The transcriptome of Mycobacterium tuberculosis in a lipid-rich dormancy model through RNAseq analysis

Tuberculosis (TB) is currently the number one killer among infectious diseases worldwide. Lipids are abundant molecules during the infectious cycle of Mycobacterium tuberculosis (Mtb) and studies better mimicking its actual metabolic state during pathogenesis are needed. Though most studies have focused on the mycobacterial lipid metabolism under standard culture conditions, little is known about the transcriptome of Mtb in a lipid environment. Here we determined the transcriptome of Mtb H37Rv in a lipid-rich environment (cholesterol and fatty acid) under aerobic and hypoxic conditions, using RNAseq. Lipids significantly induced the expression of 368 genes. A main core lipid response was observed involving efflux systems, iron caption and sulfur reduction. In co-expression with ncRNAs and other genes discussed below, may act coordinately to prepare the machinery conferring drug tolerance and increasing a persistent population. Our findings could be useful to tag relevant pathways for the development of new drugs, vaccines and new strategies to control TB

Structural Diversity in Cyclometalated Diiridium(III) Complexes with Bridging syn and anti μ2‐Oxamidato and μ2‐Dithioxamidato Ligands

Six new diiridium complexes containing 2-methyl-6-phenylpyridyl as the cyclometalating ligand with a μ2-oxamidato or a μ2-dithioxamidato ligand as the bridge have been synthesized in 60–73 % yields. These complexes were revealed by multinuclear NMR spectroscopy to contain inseparable mixtures of diastereomers (rac, ΔΔ/ΛΛ and meso, ΔΛ) with bridges in anti and syn configurations. The remarkable variety of isomers present was confirmed by X-ray crystallography on single crystals grown from mixtures of each complex. In one complex with a N,N’-bis(4-trifluoromethylphenyl)-μ2-oxamidato bridge, two single crystals of anti and syn isomers were structurally determined. Two single crystals of the μ2-dithioxamidato bridge complex were found to contain rac and meso forms of the syn isomer. Hybrid DFT computations on the four isomers of each diiridium complex revealed negligible energetic preferences for one isomer despite the methyl groups in the 2-methyl-6-phenylpyridyl cyclometalating ligands being close to the neighboring methyl groups and the bridge, thus supporting the experimental findings of isomer mixtures. Two distinct broad emissions with maxima at 522–529 nm and at 689–701 nm observed in these complexes in dichloromethane are attributed to mixed metal-ligand to ligand charge transfer (MLLCT) excited states involving the pyridyl and bridge moieties respectively with the aid of electronic structure computations

Two-loop SUSY QCD corrections to the chargino masses in the MSSM

We have calculated the two-loop strong interaction corrections to the chargino pole masses in the DRbar'-scheme in the Minimal Supersymmetric Standard Model (MSSM) with complex parameters. We have performed a detailed numerical analysis for a particular point in the parameter space and found corrections of a few tenths of a percent. We provide a computer program which calculates chargino and neutralino masses with complex parameters including the one-loop corrections and all two-loop SQCD effects.Comment: 12 pages, 11 figures, references modified, clarifications adde

Effect of the Ozonization Degree of Emu Oil over Healing: An Emerging Oxidation Treatment

This chapter deals with the ozonization process of the emu oil, the objective of this study was to quantitatively determine the peroxide value (PV) to measure the degree of ozonation, the peroxide value measures the number of peroxide groups in the ozonized oil. The ozone oxidizes the unsaturated chemical functions present in the oil giving a high cure rate for epidermal wounds. The healing process is not completely understood and there are different approaches, therefore, it was determined qualitatively if it has healing and inflammation properties, but the results of our studies have shown that the length and width of the wounds were healing quickly thanks to the peroxidation rate of the oils. In addition, both tests were correlated to obtain a greater appreciation of their functions, the mechanism involves a decrease in the inflammation of the wounds and stimulates the process of scar formation

Top pair Asymmetries at Hadron colliders with general Z′Z' couplings

Recently it has been shown that measurement of charge asymmetry of top pair production at LHC excludes any flavor violating $Z'$ vector gauge boson that could explain Tevatron forward-backward asymmetry (FBA). We consider the general form of a $Z'$ gauge boson including left-handed, right-handed vector and tensor couplings to examine FBA and charge asymmetry. To evaluate top pair asymmetries at Tevatron and LHC, we consider $B^0_q$ mixing constraints on flavor changing $Z'$ couplings and show that this model still explain forward-backward asymmetry at Tevatron and charge asymmetry can not exclude it in part of parameters space.Comment: 18 pages, 7 figure

Empirical analysis of daily cash flow time series and its implications for forecasting

Usual assumptions on the statistical properties of daily net cash flows include normality,absence of correlation and stationarity. We provide a comprehensive study based on a real-world cash flow data set showing that: (i) the usual assumption of normality, absence of correlation and stationarity hardly appear; (ii) non-linearity is often relevant for forecasting; and (iii) typical data transformations have little impact on linearity and normality. This evidence may lead to consider a more data-driven approach such as time-series forecasting in an attempt to provide cash managers with expert systems in cash management

Near-infrared spectroscopy of EX Lupi in outburst

EX Lup is the prototype of the EXor class of young eruptive stars: objects showing repetitive brightenings due to increased accretion from the circumstellar disk to the star. In this paper, we report on medium-resolution near-infrared spectroscopy of EX\,Lup taken during its extreme outburst in 2008, as well as numerical modeling with the aim of determining the physical conditions around the star. We detect emission lines from atomic hydrogen, helium, and metals, as well as first overtone bandhead emission from carbon monoxide. Our results indicate that the emission lines are originating from gas located in a dust-free region within ~ 0.2 AU of the star. The profile of the CO bandhead indicates that the CO gas has a temperature of 2500 K, and is located in the inner edge of the disk or in the outer parts of funnel flows. The atomic metals are probably co-located with the CO. Some metallic lines are fluorescently excited, suggesting direct exposure to ultraviolet photons. The Brackett series indicates emission from hot (10000 K) and optically thin gas. The hydrogen lines display a strong spectro-astrometric signal, suggesting that the hydrogen emission is probably not coming from an equatorial boundary layer; a funnel flow or disk wind origin is more likely. This picture is broadly consistent with the standard magnetospheric accretion model usually assumed for normally accreting T Tauri stars. Our results also set constraints on the eruption mechanism, supporting a model where material piles up around the corotation radius and episodically falls onto the star.Comment: 12 pages, 8 figures, 1 table, accepted for publication in Ap

On the two-loop Yukawa corrections to the MSSM Higgs boson masses at large tan(beta)

We complete the effective potential calculation of the two-loop, top/bottom Yukawa corrections to the Higgs boson masses in the Minimal Supersymmetric Standard Model, by computing the O(at^2 + at*ab + ab^2) contributions for arbitrary values of the bottom Yukawa coupling. We also compute the corrections to the minimization conditions of the effective potential at the same perturbative order. Our results extend the existing O(at^2) calculation, and are relevant in regions of the parameter space corresponding to tan(beta) >> 1. We extend to the Yukawa corrections a convenient renormalization scheme, previously proposed for the O(ab*as) corrections, that avoids unphysically large threshold effects associated with the bottom mass and absorbs the bulk of the corrections into the one-loop expression. For large values of tan(beta), the new contributions can account for a variation of several GeV in the lightest Higgs boson mass.Comment: 19 pages, 4 eps figures. Some formulae corrected in the Appendi

Precise determination of the Wtb couplings at LHC

Top pair production at LHC is the ideal place to search for nonstandard Wtb couplings in t -> W b -> l nu b decays. The lb forward-backward asymmetry in the W rest frame is very sensitive to sigma_{mu nu} couplings, and can spot one-loop QCD corrections to the decay vertex with more than 5 sigma statistical significance. We discuss the potential of this asymmetry to signal nonstandard gamma_mu and sigma_{mu nu} couplings and compare with top-antitop spin correlation asymmetries, which have a lower sensitivity. We also briefly summarise the results for Tevatron.Comment: LaTeX, 12 pages, 2 PS figures. One reference added. To be published in PR