Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human

BackgroundDilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis.MethodsWe performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts.ResultsOur results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes.ConclusionsCollectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies

MOX assay using He-4 scintillation detectors

A neutron spectroscopic technique for plutonium content measurement is described. The technique exploits the kinematic cuto of neutron emission from (α, n) reactions on oxygen. The Watt spectrum of ssion neutron emission extends to higher energies without such a cuto. 4He scintillation detectors were calibrated with an energy cut to reject neutrons of low energies, thereby making the detectors sensitive only to ssion neutrons but not to neutrons from the (α, n) reaction on oxygen. Experimental results are presented. Simulations are discussed to evaluate possible self shielding eects. Furthermore, numerous factors in uencing gamma rejection are discussed

4He detectors for Mixed Oxide (MOX) fuel measurements

A neutron spectroscopic technique for plutonium content measurement is described. The technique exploits the kinematic cutoff of neutron emission in (α,n) reactions on oxygen. The Watt spectrum of fission neutron emission extends to higher energies without such a cutoff. 4He scintillation detectors were calibrated with an energy cut to reject neutrons of low energies, thereby making the detectors sensitive only to fission neutrons but not to neutrons from the (a,n) reaction on oxygen

FLASH Portals: Radiation Portal Monitor SNM Detection using Time Correlation Techniques

The "FLASH Portals Project" is a collaboration between Arktis Radiation Detectors Ltd (CH), the Atomic Weapons Establishment (UK), and the Joint Research Centre (European Commission), supported by the Technical Support Working Group (TSWG). The program's goal was to develop and demonstrate a technology to detect shielded Special Nuclear Materials (SNM) more efficiently and less ambiguously by exploiting time correlation. This study presents experimental results of a two-sided portal monitor equipped with 16 He-4 fast neutron detectors as well as 4 polyvinyltuolene (PVT) plastic scintillators. All detectors have been synchronized to ns precision, thereby allowing to resolve time correlations from timescales of tens of microseconds (such as (n,γ) reactions) down to prompt fission correlations directly. Our results demonstrate that such correlations can be detected in a typical RPM geometry and within operationally acceptable time scales, and that exploiting these signatures significantly improves the performance of the RPM compared to neutron counting. Furthermore, the results show that some time structure remains even in the presence of heavy shielding, thus significantly improving the sensitivity of the detection system to shielded SNM.JRC.E.8-Nuclear securit

FLASH portals: radiation portal monitor SNM detection using time correlation techniques

No abstract available

Identification of novel genetic risk factors of dilated cardiomyopathy: from canine to human

Abstract Background Dilated cardiomyopathy (DCM) is a life-threatening heart disease and a common cause of heart failure due to systolic dysfunction and subsequent left or biventricular dilatation. A significant number of cases have a genetic etiology; however, as a complex disease, the exact genetic risk factors are largely unknown, and many patients remain without a molecular diagnosis. Methods We performed GWAS followed by whole-genome, transcriptome, and immunohistochemical analyses in a spontaneously occurring canine model of DCM. Canine gene discovery was followed up in three human DCM cohorts. Results Our results revealed two independent additive loci associated with the typical DCM phenotype comprising left ventricular systolic dysfunction and dilatation. We highlight two novel candidate genes, RNF207 and PRKAA2, known for their involvement in cardiac action potentials, energy homeostasis, and morphology. We further illustrate the distinct genetic etiologies underlying the typical DCM phenotype and ventricular premature contractions. Finally, we followed up on the canine discoveries in human DCM patients and discovered candidate variants in our two novel genes. Conclusions Collectively, our study yields insight into the molecular pathophysiology of DCM and provides a large animal model for preclinical studies