Effect of Reaction Parameters on the Lipase-Catalyzed Kinetic Resolution of (RS)-Metoprolol

Racemic metoprolol is a selective ß1-blocker, which is used in cardiovascular disease treatment. It has been found that (S)-metoprolol has a higher affinity to bind the ß-adrenergic receptor compared to (R)-metoprolol. Moreover, the regulatory authorities’ high market demand and guidelines have increased the preference for single enantiomer drugs. In this work, the lipase-catalyzed kinetic resolution of racemic metoprolol was performed to obtain the desired enantiomer. The type of lipase, acyl donor, and solvent were screened out. This was achieved by Candida antarctica B lipasecatalyzed transesterification of racemic metoprolol in hexane and vinyl acetate as the solvent and an acyl donor, which gave maximum conversion of (S)-metoprolol (XS) of 52%, enantiomeric excess of substrate, (ees) of 92% and product (eeP) of 90% with enantiomeric ratio (E) of 62. This method can be considered as green chemistry, which can be applied to produce other enantiopure beta-blockers

Enfermedad del Músculo Verde en pollos parrilleros Green Muscle disease in broilers

La enfermedad del Músculo Verde o enfermedad de Oregón, es el nombre común con el que se designa a la miopatía del pectoral profundo. Esta enfermedad degenerativa y oculta de los músculos de pollos parrilleros se caracteriza por atrofia y necrosis de dichos músculos. La lesión puede afectar a ambos pectorales y varía de color, desde rosa hemorrágico a una decoloración gris verdosa. Esta enfermedad es un hallazgo de consumidor, donde el aspecto organoléptico de la pechuga resulta desagradable, aunque no tiene consecuencias para la salud humana, ya que no se asocia con ningún agente infeccioso. Si las aves se comercializan enteras o en piezas con hueso, el problema no es detectado durante el procesado, lo que genera quejas del consumidor. En la comercialización de piezas deshuesadas los músculos afectados se desechan y el resto puede consumirse. Los músculos pectorales de las aves están asociados a la capacidad de volar. En el caso de los pollos parrilleros, que no desarrollan el vuelo, cuando realizan un aleteo excesivo, generalmente asociado a estrés por mal manejo al final de su producción, ocurre un aumento del pectoral profundo. El músculo quedaencerrado entre el esternón y el pectoral superficial. Cuando la presión intramuscular aumenta a niveles por encima de la presión de sangre circulante, la sangre que fluye hacia el músculo se detiene y, por estar anatómicamente atrapado por todos los lados, la presión interna del músculo impide la irrigación sanguínea, y con la continuidad del aleteo en la ausencia de oxígeno, ocurre la isquemia muscular

Adsorption of ammonium ions using activated carbon derived from artocarpus odoratissimus skin

Wastewater consists of various contaminants including ammonium ions, which are toxic to aquatic life if the concentration exceeds the standard limit. The need for finding an effective treatment to remove the pollutant is crucial, as it is difficult to remove it due to its resistance and tenacity to the environment. In this study, Artocarpus odoratissimus or commonly known as "Tarap" skin (TS) was used as a precursor for the preparation of activated carbon (AC) by two-step KOH activation. The TS was pyrolysed first at 350°C prior to KOH activation at 1:1 of impregnation ratio and 800oC of activation temperature under nitrogen gas flow in a tubular furnace. Percentage of yield, surface area, and porosity, morphology structure, surface functionalities and as well as the ability of TS based AC to adsorb ammonium ions were investigated and analysed. The properties of carbon showed that the carbon yield produced was 18.5% with a 1372.51 m2/g of surface area, 0.6756 cm3/g of pore volume and 2.1453 nm of average pore radius. The adsorption capacity of carbon at equilibrium was 1.858 mg/g. The isotherm model and kinetic study for adsorption of ammonium ions were studied using Langmuir and Freundlich, Pseudo-first order and Pseudo-second order, respectively. The equilibrium data obey the Langmuir isotherm model with the highest correlation (R 2 = 0.9373). As for the kinetic study, the adsorption process follows Pseudo-second order, which has R 2 value of 0.9964 and adsorption capacity, qe of 1.737 mg/g

Evidence for muon neutrino oscillation in an accelerator-based experiment

We present results for muon neutrino oscillation in the KEK to Kamioka (K2K) long-baseline neutrino oscillation experiment. K2K uses an accelerator-produced muon neutrino beam with a mean energy of 1.3 GeV directed at the Super-Kamiokande detector. We observed the energy dependent disappearance of muon neutrino, which we presume have oscillated to tau neutrino. The probability that we would observe these results if there is no neutrino oscillation is 0.0050% (4.0 sigma).Comment: 5 pages, 4 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Study of cosmogenic activation above ground for the DarkSide-20k experiment

The activation of materials due to exposure to cosmic rays may become an important background source for experiments investigating rare event phenomena. DarkSide-20k, currently under construction at the Laboratori Nazionali del Gran Sasso, is a direct detection experiment for galactic dark matter particles, using a two-phase liquid-argon Time Projection Chamber (TPC) filled with 49.7 tonnes (active mass) of Underground Argon (UAr) depleted in 39Ar. Despite the outstanding capability of discriminating / background in argon TPCs, this background must be considered because of induced dead time or accidental coincidences mimicking dark-matter signals and it is relevant for low-threshold electron-counting measurements. Here, the cosmogenic activity of relevant long-lived radioisotopes induced in the experiment has been estimated to set requirements and procedures during preparation of the experiment and to check that it is not dominant over primordial radioactivity; particular attention has been paid to the activation of the 120 t of UAr used in DarkSide-20k. Expected exposures above ground and production rates, either measured or calculated, have been considered in detail. From the simulated counting rates in the detector due to cosmogenic isotopes, it is concluded that activation in copper and stainless steel is not problematic. The activity of 39Ar induced during extraction, purification and transport on surface is evaluated to be 2.8% of the activity measured in UAr by DarkSide-50 experiment, which used the same underground source, and thus considered acceptable. Other isotopes in the UAr such as 37Ar and 3H are shown not to be relevant due to short half-life and assumed purification methods

Complete remission in the nephrotic syndrome study network

Background and objectives This analysis from the Nephrotic Syndrome Study Network (NEPTUNE) assessed the phenotypic and pathology characteristics of proteinuric patients undergoing kidney biopsy and defined the frequency and factors associated with complete proteinuria remission (CRever). Design, setting, participants, & measurements We enrolled adults and children with proteinuria ≥0.5 g/d at the time of first clinically indicated renal biopsy at 21 sites in North America from April 2010 to June 2014 into a prospective cohort study. NEPTUNE central pathologists assigned participants to minimal-change disease (MCD), FSGS, membranous nephropathy, or other glomerulopathy cohorts. Outcome measures for this analysis were (1) CRever with urine protein-to-creatinine ratio (UPC)<0.3 g/g with preserved native kidney function and (2) ESRD. Continuous variables are reported as median and interquartile range (IQR; 25th, 75th percentile). Cox proportional hazards modeling was used to assess factors associated with CRever. Results We enrolled 441 patients: 116 (27%) had MCD, 142 (32%) had FSGS, 66 (15%) had membranous nephropathy, and 117 (27%) had other glomerulopathy. The baseline UPC was 4.1 g/g (IQR, 1.9, 7.7) and the eGFR was 81 ml/min per 1.73 m2 (IQR, 50, 105). Median duration of observation was 19 months (IQR, 11, 30). CRever occurred in 46% of patients, and 4.6% progressed to ESRD. Multivariate analysis demonstrated that higher prebiopsy proteinuria (hazard ratio, 0.3; 95% confidence interval, 0.2 to 0.5) and pathology diagnosis (FSGS versus MCD; hazard ratio, 0.2; 95% confidence interval, 0.1 to 0.5) were inversely associated with CRever. The effect of immunosuppressive therapy on remission varied by pathology diagnosis. Conclusions In NEPTUNE, the high frequency of other pathology in proteinuric patients affirms the value of the diagnostic kidney biopsy. Clinical factors, including level of proteinuria before biopsy, pathology diagnosis, and immunosuppression, are associated with complete remission

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Sensitivity projections for a dual-phase argon TPC optimized for light dark matter searches through the ionization channel

Dark matter lighter than 10  GeV/c2 encompasses a promising range of candidates. A conceptual design for a new detector, DarkSide-LowMass, is presented, based on the DarkSide-50 detector and progress toward DarkSide-20k, optimized for a low-threshold electron-counting measurement. Sensitivity to light dark matter is explored for various potential energy thresholds and background rates. These studies show that DarkSide-LowMass can achieve sensitivity to light dark matter down to the solar neutrino fog for GeV-scale masses and significant sensitivity down to 10  MeV/c2 considering the Migdal effect or interactions with electrons. Requirements for optimizing the detector’s sensitivity are explored, as are potential sensitivity gains from modeling and mitigating spurious electron backgrounds that may dominate the signal at the lowest energies