Identification of a variant hotspot in MYBPC3 and of a novel CSRP3 autosomal recessive alteration in a cohort of Polish patients with hypertrophic cardiomyopathy

INTRODUCTION Hypertrophic cardiomyopathy (HCM) is a heart disorder caused by autosomal dominant alterations affecting both sarcomeric genes and other nonsarcomeric loci in a minority of cases. However, in some patients, the occurrence of the causal pathogenic variant or variants in homozygosity, compound heterozygosity, or double heterozygosity has also been described. Most of the HCM pathogenic variants are missense and unique, but truncating mutations of the MYBPC3 gene have been reported as founder pathogenic variants in populations from Finland, France, Japan, Iceland, Italy, and the Netherlands. OBJECTIVES This study aimed to assess the genetic background of HCM in a cohort of Polish patients. PATIENTS AND METHODS Twenty–nine Polish patients were analyzed by a next–generation sequencing panel including 404 cardiovascular genes. RESULTS Pathogenic variants were found in 41% of the patients, with ultra–rare MYBPC3 c.2541C>G (p.Tyr847Ter) mutation standing for a variant hotspot and correlating with a lower age at HCM diagnosis. Among the nonsarcomeric genes, the CSRP3 mutation was found in a single case carrying the novel c.364C>T (p.Arg122Ter) variant in homozygosity. With this finding, the total number of known HCM cases with human CSRP3 knockout cases has reached 3

Definitions and incidence of cardiac syndrome X: review and analysis of clinical data

There is no consensus regarding the definition of cardiac syndrome X (CSX). We systematically reviewed recent literature using a standardized search strategy. We included 57 articles. A total of 47 studies mentioned a male/female distribution. A meta-analysis yielded a pooled proportion of females of 0.56 (n = 1,934 patients, with 95% confidence interval: 0.54–0.59). As much as 9 inclusion criteria and 43 exclusion criteria were found in the 57 articles. Applying these criteria to a population with normal coronary angiograms and treated in 1 year at a general hospital, the attributable CSX incidence varied between 3 and 11%. The many inclusion and exclusion criteria result in a wide range of definitions of CSX and these have large effects on the incidence. This shows the need for a generally accepted definition of CSX

Verification of an electron-carbon interaction model for DSMC schemes

International audienceThe Direct Simulation Monte Carlo module of a fully kinetic 3D plasma particle code is currently under development at the Institute of Space Systems (IRS). As the complete discharge simulation of a non-stationary magnetoplasmadynamic thruster is intended, improved models for the DSMC (direct simulation monte carlo) based interaction evaluation in a highly rarefied and strongly disturbed plasma need to be used. For that purpose it is essential to avoid macroscopic quantities (like temperature) in the model approach. Therefore, a collision and reaction evaluation approach was developed and implemented which is based on energy dependent cross section data only. As the thruster propellant is Polytetrafluorethylen (PTFE) a large cross section data base was built, implemented, and verified based on the assumption of an initially fully dissociated and partially ionized plasma. The electron - heavy particle interactions of interest are elastic scattering (including polarization), collisional excitation, de-excitation, and recombination. In this work we present the model approach, details on the implemented Carbon related cross sections as well as the verification procedure which is based on the reproduction of rate coefficients in the range of 20.000 - 200.000 K. © 2010 by the authors

Experimental and Numerical Techniques to Assess Catalysis

Catalytic heating can be a significant portion of the thermal load experienced by a body during re-entry. Under the auspices of the NATO Research and Technology Organisation Applied Vehicle Technologies Panel Task Group AVT-136 an assessment of the current state-of-the-art in the experimental characterization and numerical simulation of catalysis on high-temperature material surfaces has been conducted. This paper gives an extraction of the final report for this effort, showing the facilities and capabilities worldwide to assess catalysis data. A corresponding summary for the modeling activities is referenced in this article

Numerical Simulation of Instationary Magnetoplasmadynamic Thrusters

In order to model rarefied plasma flows under conditions where continuum assumptions fail, a cooperation between IRS (Institute of Space Systems, University of Stuttgart), IAG (Institute for Aerodynamics and Gas Dynamics, University of Stuttgart), HLRS (High Performance Computing Center Stuttgart) and IHM (Institute for Pulsed Power and Microwave Technology, Research Center Karlsruhe) has been formed. Within the project "Modeling and Simulation on High Performance Computers", which is funded by the Landesstiftung Baden-Württemberg, a scheme for solving the Boltzmann equation for rarefied, non-continuum plasma flows is under development, making use of well known approaches from PIC (Particle in Cell) and DSMC (Direct Simulation Monte Carlo). The modeling will be explained in some detail and required computational resources will be estimated

Advanced scaling model for simplified thrust and power scaling of an applied-field magnetoplasmadynamic thruster

IRS and Alta are currently involved in ESA and EU (HIPER) programs aiming for the development of high power electric propulsion systems. In the framework of these programs, two 100 kW applied-field magnetoplasmadynamic thrusters (AF-MDPT) are to be developed and tested within 2011: The steady state gas-fed AF-MPD ZT2 and Alta gas-fed pulsed AFMPD thruster. Such devices present some of the best propulsion systems if it comes to high thrust density and high specific impulse requirements, for example in orbit raising or Mars transfer mission scenarios. However, up to this day, there exists no adequate simple scaling model for AF-MPDT available to mission analysis and engine design which is addressed in this work: The classic Tikhonov model is extended and improved for steady state gas fed AFMPDT. A simplified law of energy conservation is introduced, which can be extended with an improved anode loss model. Both models were fitted using data of existing thrusters. Further, a common envelope of both thrusters has been achieved by overlapping of operational conditions to allow a comparison of both designs. Also, power scaling and performance estimation of the 100 kW IRS AF-MPD ZT1 and the 100 kW Alta AF-MPD thruster are presented in this paper. The knowledge obtained is going to enable IRS andAlta to define the specifications of a future ESA/European AF-MPDT