59 research outputs found

    Accessory mitral valve tissue causing severe left ventricular outflow tract obstruction in a post-Senning patient with transposition of the great arteries

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    Accessory mitral valve tissue is a rare congenital anomaly associated with congenital cardiac defects and is usually detected in the first decade of life. We describe the case of an 18-year old post-Senning asymptomatic patient who was found to have accessory mitral valve tissue on transthoracic echocardiography producing severe left ventricular outflow tract obstruction

    SETD2 haploinsufficiency for microtubule methylation is an early driver of genomic instability in renal cell carcinoma

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    Loss of the short arm of chromosome 3 (3p) occurs early in >95% of clear cell renal cell carcinoma (ccRCC). Nearly ubiquitous 3p loss in ccRCC suggests haploinsufficiency for 3p tumor suppressors as early drivers of tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located in the 3p deletion, to also trimethylate microtubules on lysine 40 (aTubK40me3) during mitosis, with aTubK40me3 required for genomic stability. We now show that monoallelic, Setd2-deficient cells retaining H3K36me3, but not aTubK40me3, exhibit a dramatic increase in mitotic defects and micronuclei count, with increased viability compared with biallelic loss. In SETD2-inactivated human kidney cells, rescue with a pathogenic SETD2 mutant deficient for microtubule (aTubK40me3), but not histone (H3K36me3) methylation, replicated this phenotype. Genomic instability (micronuclei) was also a hallmark of patient-derived cells from ccRCC. These data show that the SETD2 tumor suppressor displays a haploinsufficiency phenotype disproportionately impacting microtubule methylation and serves as an early driver of genomic instability. Significance: Loss of a single allele of a chromatin modifier plays a role in promoting oncogenesis, underscoring the growing relevance of tumor suppressor haploinsufficiency in tumorigenesis

    Effects of annealing treatment prior to cold rolling on delayed fracture properties in ferrite-austenite duplex lightweight steels

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    Tensile properties of recently developed automotive high-strength steels containing about 10 wt pct of Mn and Al are superior to other conventional steels, but the active commercialization has been postponed because they are often subjected to cracking during formation or to the delayed fracture after formation. Here, the delayed fracture behavior of a ferrite-austenite duplex lightweight steel whose microstructure was modified by a batch annealing treatment at 1023 K (750 A degrees C) prior to cold rolling was examined by HCl immersion tests of cup specimens, and was compared with that of an unmodified steel. After the batch annealing, band structures were almost decomposed as strong textures of {100}aOE (c) 011 > alpha-fibers and {111}aOE (c) 112 > gamma-fibers were considerably dissolved, while ferrite grains were refined. The steel cup specimen having this modified microstructure was not cracked when immersed in an HCl solution for 18 days, whereas the specimen having unmodified microstructure underwent the delayed fracture within 1 day. This time delayed fracture was more critically affected by difference in deformation characteristics such as martensitic transformation and deformation inhomogeneity induced from concentration of residual stress or plastic strain, rather than the difference in initial microstructures. The present work gives a promise for automotive applications requiring excellent mechanical and delayed fracture properties as well as reduced specific weight.ope

    Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

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    BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

    Polymorphism: an evaluation of the potential risk to the quality of drug products from the Farmácia Popular Rede Própria

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    The Physics of the B Factories

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    Comparative Study of Crosstalk Reduction Techniques for Parallel Microstriplines

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    Performance analysis of integrated gasification combined cycle considering turbine modification

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    Paper presented at the 7th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Turkey, 19-21 July, 2010.In IGCC plants, the operating environment of the gas turbine changes from its designed condition due to its integration with the gasifier block, especially with the air separation unit. The theoretical IGCC power and efficiency enhances as the integration degree becomes lower. However, low integration degree designs would reduce the compressor surge margin and cause overheating of turbine metal considerably. The main reason for these problems is that turbine inlet gas flow increases considerably because the heating value of the syngas is much lower than that of natural gas and also additional air is supplied by the auxiliary compressor. The problems can be mitigated by modulating gas turbine operating parameters. However, the problems can better be overcome through modifications of gas turbine components. This study analyzed the modification of the turbine to accommodate the increased turbine flow. The entire IGCC plant was modeled and a full off­-design operation of the gas turbine was simulated. The performances of the IGCC plant with and without the turbine modification were compared. The limitations of the compressor surge margin and the turbine blade temperature were applied in both cases. The turbine modification enables a larger net power output in the low integration degree regime. The net plant efficiency does not depend very much on the integration degree.ksb201

    Performance analysis of integrated gasification combined cycle considering turbine modification

    No full text
    Paper presented at the 7th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Turkey, 19-21 July, 2010.In IGCC plants, the operating environment of the gas turbine changes from its designed condition due to its integration with the gasifier block, especially with the air separation unit. The theoretical IGCC power and efficiency enhances as the integration degree becomes lower. However, low integration degree designs would reduce the compressor surge margin and cause overheating of turbine metal considerably. The main reason for these problems is that turbine inlet gas flow increases considerably because the heating value of the syngas is much lower than that of natural gas and also additional air is supplied by the auxiliary compressor. The problems can be mitigated by modulating gas turbine operating parameters. However, the problems can better be overcome through modifications of gas turbine components. This study analyzed the modification of the turbine to accommodate the increased turbine flow. The entire IGCC plant was modeled and a full off­-design operation of the gas turbine was simulated. The performances of the IGCC plant with and without the turbine modification were compared. The limitations of the compressor surge margin and the turbine blade temperature were applied in both cases. The turbine modification enables a larger net power output in the low integration degree regime. The net plant efficiency does not depend very much on the integration degree.ej201
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