Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus

Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidney disease, we found the 129S6 mouse strain to be very susceptible to the development of hypertension, albuminuria, and kidney injury, whereas the C57BL/6 strain is relatively resistant. Accordingly, we set out to map quantitative trait loci conferring susceptibility to hypertension and albuminuria using this model with F2 mice. We found significant linkage of the blood pressure trait to two loci. At D11Mit143, mice homozygous for the 129S6 allele had significantly higher systolic blood pressure than mice heterozygous or homozygous for the C57BL/6 allele. Similarly, at D1Mit308, there was an excellent correlation between genotype and the blood pressure phenotype. The effect of the chromosome 11 locus was verified with a separate cohort of F2 mice. For the albuminuria trait, a significant locus was found at D11Mit143, which overlaps the blood pressure trait locus. Our studies have identified a region spanning ∼8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD

Examination of the astrophysical S-factors of the radiative proton capture on 2H, 6Li, 7Li, 12C and 13C

Astrophysical S-factors of radiative capture reactions on light nuclei have been calculated in a two-cluster potential model, taking into account the separation of orbital states by the use of Young schemes. The local two-body potentials describing the interaction of the clusters were determined by fitting scattering data and properties of bound states. The many-body character of the problem is approximatively accounted for by Pauli forbidden states. An important feature of the approach is the consideration of the dependence of the interaction potential between the clusters on the orbital Young schemes, which determine the permutation symmetry of the nucleon system. Proton capture on 2H, 6Li, 7Li, 12C, and 13C was analyzed in this approach. Experimental data at low energies were described reasonably well when the phase shifts for cluster-cluster scattering, extracted from precise data, were used. This shows that decreasing the experimental error on differential elastic scattering cross sections of light nuclei at astrophysical energies is very important also to allow a more accurate phase shift analysis. A future increase in precision will allow more definite conclusions regarding the reaction mechanisms and astrophysical conditions of thermonuclear reactions.Comment: 40p., 9 fig., 83 ref. arXiv admin note: substantial text overlap with arXiv:1005.1794, arXiv:1112.1760, arXiv:1005.198

Germline Analysis from Tumor–Germline Sequencing Dyads to Identify Clinically Actionable Secondary Findings

To evaluate germline variants in hereditary cancer susceptibility genes among unselected cancer patients undergoing tumor-germline sequencing

Unfolding of differential energy spectra in the MAGIC experiment

The paper describes the different methods, used in the MAGIC experiment, to unfold experimental energy distributions of cosmic ray particles (gamma-rays). Questions and problems related to the unfolding are discussed. Various procedures are proposed which can help to make the unfolding robust and reliable. The different methods and procedures are implemented in the MAGIC software and are used in most of the analyses.Comment: Submitted to NIM

Global stability for a class of virus models with CTL immune response and antigenic variation

We study the global stability of a class of models for in-vivo virus dynamics, that take into account the CTL immune response and display antigenic variation. This class includes a number of models that have been extensively used to model HIV dynamics. We show that models in this class are globally asymptotically stable, under mild hypothesis, by using appropriate Lyapunov functions. We also characterise the stable equilibrium points for the entire biologically relevant parameter range. As a byproduct, we are able to determine what is the diversity of the persistent strains.Comment: 15 page

A Mouse Model of Heritable Cerebrovascular Disease

The study of animal models of heritable cerebrovascular diseases can improve our understanding of disease mechanisms, identify candidate genes for related human disorders, and provide experimental models for preclinical trials. Here we describe a spontaneous mouse mutation that results in reproducible, adult-onset, progressive, focal ischemia in the brain. The pathology is not the result of hemorrhage, embolism, or an anatomical abnormality in the cerebral vasculature. The mutation maps as a single site recessive locus to mouse Chromosome 9 at 105 Mb, a region of shared synteny with human chromosome 3q22. The genetic interval, defined by recombination mapping, contains seven protein-coding genes and one processed transcript, none of which are changed in their expression level, splicing, or sequence in affected mice. Targeted resequencing of the entire interval did not reveal any provocative changes; thus, the causative molecular lesion has not been identified

Achieving stationary high performance plasmas at Wendelstein 7-X

This work reports on recent results on the search for high performance plasma scenarios at the magnetically confined stellarator fusion device Wendelstein 7-X. In four new designed scenarios, the development from transient toward stationary plasmas of improved performance has been realized. In particular, a high performance duration of up to 5 s, an energy confinement time of 0.3 s, a diamagnetic energy of 1.1 MJ, a central ion temperature of 2.2 keV, and a fusion triple product of 3:4 1019 m3 keV s have been achieved, and previously observed limitations of the machine have been overcome, regarding both the performance and its duration. The two main experimental techniques for stationary high performance are neutral beam injection core fueling on the one hand and the use of a magnetic field configuration with internal islands on the other hand. Two of the developed scenarios are expected to be extendable straightforward toward a duration of several tens of seconds, making use of the long pulse operation capabilities of W7-X