308 research outputs found
Application of FFTBM with signal mirroring to improve accuracy assessment of MELCOR code
This paper deals with the application of Fast Fourier Transform Base Method (FFTBM) with signal mirroring
(FFTBM-SM) to assess accuracy of MELCOR code. This provides deeper insights into how the accuracy
of MELCOR code in predictions of thermal-hydraulic parameters varies during transients. The case studied
was modeling of Station Black-Out (SBO) accident in PSB-VVER integral test facility by MELCOR code.
The accuracy of this thermal-hydraulic modeling was previously quantified using original FFTBM in a few
number of time-intervals, based on phenomenological windows of SBO accident. Accuracy indices calculated
by original FFTBM in a series of time-intervals unreasonably fluctuate when the investigated signals
sharply increase or decrease. In the current study, accuracy of MELCOR code is quantified using FFTBMSM
in a series of increasing time-intervals, and the results are compared to those with original FFTBM.
Also, differences between the accuracy indices of original FFTBM and FFTBM-SM are investigated and correction
factors calculated to eliminate unphysical effects in original FFTBM. The main findings are: (1)
replacing limited number of phenomena-based time-intervals by a series of increasing time-intervals
provides deeper insights about accuracy variation of the MELCOR calculations, and (2) application of
FFTBM-SM for accuracy evaluation of the MELCOR predictions, provides more reliable results than original
FFTBM by eliminating the fluctuations of accuracy indices when experimental signals sharply
increase or decrease. These studies have been performed in the framework of a research project, aiming
to develop an appropriate accident management support tool for Bushehr nuclear power plant.
2016 Elsevier B.V. All rights reserved
New turbulence modeling for simulation of Direct Contact Condensation in two-phase pressurized thermal shock
Injection of Emergency Core Cooling System (ECCS) water into the primary loops of the Pressurized Water
Reactors (PWRs) leads to rapid cooling of Reactor Pressure Vessel (RPV) inside wall after Loss Of Coolant
Accident (LOCA). This condition, known as Pressurized Thermal Shock (PTS) intensifies the propagation of the
RPV structural defects and would be considered as an ageing mechanism. For structural and fracture analysis of
RPV wall, thermal-hydraulic analysis of PTS should be accomplished to obtain the steam/water flow characteristics
in the downcomer. For this purpose, simulation of steam/water stratified flow (due to density difference)
after the injection point should be done by Computational Fluid Dynamics (CFD) methods. In this
region, steam condensation over water layer is considered as the only heat source and controlled by turbulence
eddy motion near the steam/water interface. Based on Surface Renewal Theory (SRT), Heat Transfer Coefficient
(HTC) would be calculated by evaluation of turbulence length and velocity. Therefore, prediction of turbulence
characteristics plays a significant role for estimation of interfacial mass transfer and temperature profile. High
gradient of velocity and Turbulence Kinetic Energy (TKE), and interfacial mass and momentum transfer at the
steam/water interface needs some modifications for application of traditional turbulence models.
Implementation of damping function is one of the common solutions to overcome the overestimation of TKE at
the steam/water interface. Although, this function improves flow characteristics of smooth stratified flow, investigation
of conservation equations and experimental data implies that the other source function is needed
when the flow regime changes to wavy flow. In this paper, a new source function of TKE based on variations of
turbulence characteristics is proposed for steam/water interface leading to a special boundary condition of
turbulence. To investigate the effects of this modification, simulation of air/water and steam/water stratified
flow in three different test facilities is performed. The results show that the implementation of the source
function of TKE improves the prediction of turbulence characteristics at the interface of isothermal stratified
flow. Also condensation rate and temperature gradient of steam/water stratified flow have a better agreement
with experimental data
COMPARATIVE EFFECTS OF NITRAZEPAM AND ACTH ON THE TREATMENT OF INFANTILE SPASM
ObjectiveInfantile spasms (IS) or West syndrome is a convulsive disease characterized by brief, symmetric axial muscle contractions (neck, trunk, and/or extremities).The therapy universally recognized as most effective in the treatment of IS, is treatment with the adrenocorticotropic hormone (ACTH) or oral corticosteroids. This therapy however has important side effects. Many studies have sought to find alternative therapies with fewer side effects. Nitrazepam, it has been proven, can be as effective as ACTH in controlling infantile spasms. The aim of this study was to evaluate and compare the efficacy of Nitrazepam and ACTH on the treatment of infantile spasms. Materials & MethodsThis randomized controlled clinical trial, enrolled sixty patients with newly diagnosed and previously untreated IS; diagnosis was made based on the criteria of The International Classification of Epilepsies of the International League Against Epilepsy (ILAE). Prior to treatment, all patients underwent Electro encephalo graphs (EEGs) and CT scans. Patients were randomized to receive 0.5-1 mg/kg Nitrazpam (NZP) in three daily doses or 40 IU Depot ACTH in a single morning dose. Complete cessation of spasms was considered to be as optimal response.ResultsOf the sixty patients studied, 24 (40%) were girls and 36(60%) were boys. All patients in the both groups were matched for age and sex.There were no differences between the both groups regarding age and sex (non-significant). Following treatments, at the end of the 6-week duration therapy, optimal response (Cessation of spasms) was obtained in 19 (63%) patients of NZP group and 9 (30%) patients of ACTH group, (
Eplerenone attenuates pathological pulmonary vascular rather than right ventricular remodeling in pulmonary arterial hypertension
BACKGROUND: Aldosterone is a mineralocorticoid hormone critically involved in arterial blood pressure regulation. Although pharmacological aldosterone antagonism reduces mortality and morbidity among patients with severe left-sided heart failure, the contribution of aldosterone to the pathobiology of pulmonary arterial hypertension (PAH) and right ventricular (RV) heart failure is not fully understood. METHODS: The effects of Eplerenone (0.1% Inspra® mixed in chow) on pulmonary vascular and RV remodeling were evaluated in mice with pulmonary hypertension (PH) caused by Sugen5416 injection with concomitant chronic hypoxia (SuHx) and in a second animal model with established RV dysfunction independent from lung remodeling through surgical pulmonary artery banding. RESULTS: Preventive Eplerenone administration attenuated the development of PH and pathological remodeling of pulmonary arterioles. Therapeutic aldosterone antagonism - starting when RV dysfunction was established - normalized mineralocorticoid receptor gene expression in the right ventricle without direct effects on either RV structure (Cardiomyocyte hypertrophy, Fibrosis) or function (assessed by non-invasive echocardiography along with intra-cardiac pressure volume measurements), but significantly lowered systemic blood pressure. CONCLUSIONS: Our data indicate that aldosterone antagonism with Eplerenone attenuates pulmonary vascular rather than RV remodeling in PAH
Identification of splice defects due to noncanonical splice site or deep‐intronic variants in ABCA4
Pathogenic variants in the ATP-binding cassette transporter A4 (ABCA4) gene cause a continuum of retinal disease phenotypes, including Stargardt disease. Noncanonical splice site (NCSS) and deep-intronic variants constitute a large fraction of disease-causing alleles, defining the functional consequences of which remains a challenge. We aimed to determine the effect on splicing of nine previously reported or unpublished NCSS variants, one near exon splice variant and nine deep-intronic variants in ABCA4, using in vitro splice assays in human embryonic kidney 293T cells. Reverse transcription-polymerase chain reaction and Sanger sequence analysis revealed splicing defects for 12 out of 19 variants. Four deep-intronic variants create pseudoexons or elongate the upstream exon. Furthermore, eight NCSS variants cause a partial deletion or skipping of one or more exons in messenger RNAs. Among the 12 variants, nine lead to premature stop codons and predicted truncated ABCA4 proteins. At least two deep-intronic variants affect splice enhancer and silencer motifs and, therefore, these conserved sequences should be carefully evaluated when predicting the outcome of NCSS and deep-intronic variants
PASANDO REVISTA A LAS TROPAS EN LA LLEGADA DEL REY [Material gráfico]
Copia digital. Madrid : Ministerio de Educación, Cultura y Deporte. Subdirección General de Coordinación Bibliotecaria, 201
Phosphodiesterase-5 Inhibition Mimics Intermittent Reoxygenation and Improves Cardioprotection in the Hypoxic Myocardium
Although chronic hypoxia is a claimed myocardial risk factor reducing tolerance to ischemia/reperfusion (I/R), intermittent reoxygenation has beneficial effects and enhances heart tolerance to I/R. Aim of the study: To test the hypothesis that, by mimicking intermittent reoxygenation, selective inhibition of phosphodiesterase-5 activity improves ischemia tolerance during hypoxia. Adult male Sprague-Dawley rats were exposed to hypoxia for 15 days (10% O2) and treated with placebo, sildenafil (1.4 mg/kg/day, i. p.), intermittent reoxygenation (1 h/day exposure to room air) or both. Controls were normoxic hearts. To assess tolerance to I/R all hearts were subjected to 30-min regional ischemia by left anterior descending coronary artery ligation followed by 3 h-reperfusion. Whereas hypoxia depressed tolerance to I/R, both sildenafil and intermittent reoxygenation reduced the infarct size without exhibiting cumulative effects. The changes in myocardial cGMP, apoptosis (DNA fragmentation), caspase-3 activity (alternative marker for cardiomyocyte apoptosis), eNOS phosphorylation and Akt activity paralleled the changes in cardioprotection. However, the level of plasma nitrates and nitrites was higher in the sildenafil+intermittent reoxygenation than sildenafil and intermittent reoxygenation groups, whereas total eNOS and Akt proteins were unchanged throughout. Conclusions: Sildenafil administration has the potential to mimic the cardioprotective effects led by intermittent reoxygenation, thereby opening the possibility to treat patients unable to be reoxygenated through a pharmacological modulation of NO-dependent mechanisms
cGMP becomes a drug target
Cyclic guanosine 3′,5′-monophosphate (cGMP) serves as a second messenger molecule, which regulates pleiotropic cellular functions in health and disease. cGMP is generated by particulate or soluble guanylyl cyclases upon stimulation with natriuretic peptides or nitric oxide, respectively. Furthermore, the cGMP concentration is modulated by cGMP-degrading phosphodiesterases. Several targets of cGMP are utilized to effect its various cellular functions. These effector molecules comprise cGMP-dependent protein kinases, ion channels, and phosphodiesterases. During the last decade, it emerged that cGMP is a novel drug target for the treatment of pulmonary and cardiovascular disorders. In this respect, several drugs were developed, which are now in clinical phase studies for, e.g., pulmonary hypertension or cardiovascular diseases. These new drugs act NO-independently with/without heme on soluble guanylyl cyclases or induce subtypes of particular guanylyl cyclases and thereby lead to new therapeutic concepts and horizons. In this regard, the fifth cGMP meeting held in June 2011 in Halle, Germany, comprised the new therapeutic challenges with the novel functional and structural concepts of cGMP generating and effector molecules. This report summarizes the new data on molecular mechanisms, (patho)physiological relevance, and therapeutic potentials of the cGMP signaling system that were presented at this meeting
Survival with sildenafil and inhaled iloprost in a cohort with pulmonary hypertension: an observational study
Demographics, clinical characteristics, health resource utilization and cost of chronic thromboembolic pulmonary hypertension patients: retrospective results from six European countries
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