OBSCN Mutations Associated with Dilated Cardiomyopathy and Haploinsufficiency

Studies of the functional consequences of DCM-causing mutations have been limited to a few cases where patients with known mutations had heart transplants. To increase the number of potential tissue samples for direct investigation we performed whole exon sequencing of explanted heart muscle samples from 30 patients that had a diagnosis of familial dilated cardiomyopathy and screened for potentially disease-causing mutations in 58 HCM or DCM-related genes.We identified 5 potentially disease-causing OBSCN mutations in 4 samples; one sample had two OBSCN mutations and one mutation was judged to be not disease-related. Also identified were 6 truncating mutations in TTN, 3 mutations in MYH7, 2 in DSP and one each in TNNC1, TNNI3, MYOM1, VCL, GLA, PLB, TCAP, PKP2 and LAMA4. The mean level of obscurin mRNA was significantly greater and more variable in healthy donor samples than the DCM samples but did not correlate with OBSCN mutations. A single obscurin protein band was observed in human heart myofibrils with apparent mass 960 ± 60 kDa. The three samples with OBSCN mutations had significantly lower levels of obscurin immunoreactive material than DCM samples without OBSCN mutations (45±7, 48±3, and 72±6% of control level).Obscurin levels in DCM controls, donor heart and myectomy samples were the same.OBSCN mutations may result in the development of a DCM phenotype via haploinsufficiency. Mutations in the obscurin gene should be considered as a significant causal factor of DCM, alone or in concert with other mutations

Scattering solutions of the spinless Salpeter equation

A method to compute the scattering solutions of a spinless Salpeter equation (or a Schrodinger equation) with a central interaction is presented. This method relies on the 3-dimensional Fourier grid Hamiltonian method used to compute bound states. It requires only the evaluation of the potential at equally spaced grid points and yields the radial part of the scattering solution at the same grid points. It can be easily extended to the case of coupled channel equations and to the case of non-local interactions.Comment: 7 page

Staggered Flux Phase in a Model of Strongly Correlated Electrons

We present numerical evidence for the existence of a staggered flux (SF) phase in the half-filled two-leg t-U-V-J ladder, with true long-range order in the counter-circulating currents. The density-matrix renormalization-group (DMRG) / finite-size scaling approach, generalized to describe complex-valued Hamiltonians and wavefunctions, is employed. The SF phase exhibits robust currents at intermediate values of the interaction strength.Comment: Version to appear in Phys. Rev. Let

Environmental hydro-refugia demonstrated by vegetation vigour in the Okavango Delta, Botswana

Climate shifts at decadal scales can have environmental consequences, and therefore, identifying areas that act as environmental refugia is valuable in understanding future climate variability. Here we illustrate how, given appropriate geohydrology, a rift basin and its catchment can buffer vegetation response to climate signals on decadal time-scales, therefore exerting strong local environmental control. We use time-series data derived from Normalised Difference Vegetation Index (NDVI) residuals that record vegetation vigour, extracted from a decadal span of MODIS images, to demonstrate hydrogeological buffering. While this has been described previously it has never been demonstrated via remote sensing and results in relative stability in vegetation vigour inside the delta, compared to that outside. As such the Delta acts as a regional hydro-refugium. This provides insight, not only to the potential impact of future climate in the region, but also demonstrates why similar basins are attractive to fauna, including our ancestors, in regions like eastern Africa. Although vertebrate evolution operates on time scales longer than decades, the sensitivity of rift wetlands to climate change has been stressed by some authors, and this work demonstrates another example of the unique properties that such basins can afford, given the right hydrological conditions

ANTLER statistical analysis plan, Version 3, 16 January 2020

This analysis plan sets out the methods of analysing the predetermined primary, secondary and health economic outcomes for ANTLER, which will be reported in the National Institute for Health Research, Health Technology Assessment report at the end of the trial and also in the main peer review paper(s) to result from this randomised controlled trial. The analysis and reporting of this trial will conform to the CONSORT and CHEERS statements and the appropriate standard operating procedures written by Priment Clinical Trials Unit. Further information on this trial can be found in the protocol version 7.0 (26/11/2018). The protocol is stored on: S:\Pop_Health\PCPH_Priment\Projects\Current\CTIMPS\ANTLER\6. Protocol\ANTLER_protocol_v7_20181126.pdf

High Resolution Infrared Imaging and Spectroscopy of the Pistol Nebula: Evidence for Ejection

We present new NICMOS/HST infrared images and CGS4/UKIRT Br-alpha (4.05 um) spectroscopy of the Pistol Star and its associated nebula, finding strong evidence to support the hypothesis that the Pistol Nebula was ejected from the Pistol Star. The Pa-alpha NICMOS image shows that the nebula completely surrounds the Pistol Star, although the line intensity is much stronger on its northern and western edges. The Br-alpha spectra show the classical ring-like signature of quasi-spherical expansion, with weak blueshifted emission (V_max approx -60 km/s) and strong redshifted emission (V_max approx +10 km/s), where the velocities are with respect to the velocity of the Pistol Star; further, the redshifted emission appears to be "flattened" in the position-velocity diagram. These data suggest that the nebula was ejected from the star several thousand years ago, with a velocity between the current terminal velocity of the stellar wind (95 km/s) and the present expansion velocity of gas in the outer shell of the nebula (60 km/s). The Pa-alpha image reveals several emission-line stars in the region, including two newly-identified emission-line stars north of the Pistol Star with spectral types earlier than WC8 (T_eff > 50,000 K). The presence of these stars, the morphology of the Pa-alpha emission, and the velocity field in the gas suggest that the side of the nebula furthest from us is approaching, and being ionized by, the hot stars of the Quintuplet, and that the highest velocity redshifted gas has been decelerated by winds from the Quintuplet stars. We also discuss the possibility that the nebular gas might be magnetically confined by the ambient magnetic field delineated by the nearby nonthermal filaments.Comment: Figure 1 is included as a JPG file. Figure 1 and 2 also available at ftp://quintup.astro.ucla.edu/pistol2