Recurrent inversion polymorphisms in humans associate with genetic instability and genomic disorders

Unlike copy number variants (CNVs), inversions remain an underexplored genetic variation class. By integrating multiple genomic technologies, we discover 729 inversions in 41 human genomes. Approximately 85% of inversions <2 kbp form by twin-priming during L1 retrotransposition; 80% of the larger inversions are balanced and affect twice as many nucleotides as CNVs. Balanced inversions show an excess of common variants, and 72% are flanked by segmental duplications (SDs) or retrotransposons. Since flanking repeats promote non-allelic homologous recombination, we developed complementary approaches to identify recurrent inversion formation. We describe 40 recurrent inversions encompassing 0.6% of the genome, showing inversion rates up to 2.7 × 10(-4) per locus per generation. Recurrent inversions exhibit a sex-chromosomal bias and co-localize with genomic disorder critical regions. We propose that inversion recurrence results in an elevated number of heterozygous carriers and structural SD diversity, which increases mutability in the population and predisposes specific haplotypes to disease-causing CNVs

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase

Conductance enhancement in quantum-point-contact semiconductor-superconductor devices .

We present numerical calculations of the conductance of an interface between a phase-coherent two-dimensional electron gas and a superconductor with a quantum point contact in the normal region. Using a scattering matrix approach we reconsider the geometry of De Raedt, Michielsen, and Klapwijk [Phys. Rev. B 50, 631 (1994)] which was studied within the time-dependent Bogoliubov�de Gennes formalism. We find that the factor-of-2 enhancement of the conductance GNS compared to the normal state conductance GN for ideal interfaces may be suppressed for interfaces with a quantum point contact with only a few propagating modes. The suppression is found to depend strongly on the position of the Fermi level. We also study the suppression due to a barrier at the interface and find an anomalous behavior caused by quasiparticle interference. Finally, we consider the limit of sequential tunneling and find a suppression of the factor-of-2 enhancement which may explain the absence of conductance enhancement in experiments on metal-superconductor structures

Tokamak ignition/burn experimental research device

As part of a continuing effort by the Office of Fusion Energy to define an ignition experiment, a superconducting tokamak has been designed with thin neutron shielding and aggressive magnet and plasma parameters. By so minimizing the inner radial dimensions of the tokamak center post, coil, and shielding region, the plasma major radius is reduced with a corresponding reduction in device costs. The peak nuclear-heating rate in the superconducting TF coils is 22 mW/cm/sup 3/, which results in a steady heat load to the cryogenic system of 50 kW. Fast-wave, lower-hybrid heating would be used to induce a 10-MA current in a moderate density plasma. Then pellet fueling would raise the density to achieve ignition as the current decays in a few hundred seconds. Steady-state current drive in subignited conditions permits a 0.8 MW/m/sup 2/ average wall loading to study plasma and nuclear engineering effects