448 research outputs found

    ICONE10-22646 AN IMPROVED MODEL FOR POSTULATING FABRICATION FLAWS IN REACTOR PRESSURE VESSELS FOR STRUCTURAL INTEGRITY EVALUATION

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    ABSTRACT This paper presents an improved model for postulating fabrication flaws in reactor pressure vessels (RPVs) and for the treatment of measured flaw data by probabilistic fracture mechanics (PFM) codes that are used for structural integrity evaluations. The model used to develop the current pressurized thermal shock (PTS) regulations conservatively postulated that all fabrication flaws were inner-surface breaking flaws. To reduce conservatisms and uncertainties in flaw-related inputs

    Technical Letter Report Development of Flaw Size Distribution Tables Including Effects of Flaw Depth Sizing Errors for Draft 10CFR 50.61a (Alternate PTS Rule) JCN-N6398, Task 4

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    This document describes a new method to determine whether the flaws in a particular reactor pressure vessel are consistent with the assumptions regarding the number and sizes of flaws used in the analyses that formed the technical justification basis for the new voluntary alternative Pressurized Thermal Shock (PTS) rule (Draft 10 CFR 50.61a). The new methodology addresses concerns regarding prior methodology because ASME Code Section XI examinations do not detect all fabrication flaws, they have higher detection performance for some flaw types, and there are flaw sizing errors always present (e.g., significant oversizing of small flaws and systematic under sizing of larger flaws). The new methodology allows direct comparison of ASME Code Section XI examination results with values in the PTS draft rule Tables 2 and 3 in order to determine if the number and sizes of flaws detected by an ASME Code Section XI examination are consistent with those assumed in the probabilistic fracture mechanics calculations performed in support of the development of 10 CFR 50.61a

    Amiodarone disrupts cholesterol biosynthesis pathway and causes accumulation of circulating desmosterol by inhibiting 24-dehydrocholesterol reductase

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    Background We have earlier reported that amiodarone, a potent and commonly used antiarrhythmic drug increases serum desmosterol, the last precursor of cholesterol, in 20 cardiac patients by an unknown mechanism. Objective Here, we extended our study to a large number of cardiac patients of heterogeneous diagnoses, evaluated the effects of combining amiodarone and statins (inhibitors of cholesterol synthesis at the rate-limiting step of hydroxy-methyl-glutaryl CoA reductase) on desmosterol levels and investigated the mechanism(s) by which amiodarone interferes with the metabolism of desmosterol using in vitro studies. Methods and Results We report in a clinical case-control setting of 236 cardiac patients (126 with and 110 without amiodarone treatment) that amiodarone medication is accompanied by a robust increase in serum desmosterol levels independently of gender, age, body mass index, cardiac and other diseases, and the use of statins. Lipid analyses in patient samples taken before and after initiation of amiodarone therapy showed a systematic increase of desmosterol upon drug administration, strongly arguing for a direct causal link between amiodarone and desmosterol accumulation. Mechanistically, we found that amiodarone resulted in desmosterol accumulation in cultured human cells and that the compound directly inhibited the 24-dehydrocholesterol reductase (DHCR24) enzyme activity. Conclusion These novel findings demonstrate that amiodarone blocks the cholesterol synthesis pathway by inhibiting DHCR24, causing a robust accumulation of cellular desmosterol in cells and in the sera of amiodarone-treated patients. It is conceivable that the antiarrhythmic potential and side effects of amiodarone may in part result from inhibition of the cholesterol synthesis pathway.Peer reviewe
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