Compound heterozygosity of predicted loss-of-function DES variants in a family with recessive desminopathy

Background: Variants in the desmin gene (DES) are associated with desminopathy; a myofibrillar myopathy mainly characterized by muscle weakness, conduction block, and dilated cardiomyopathy. To date, only ~50 disease-associated variants have been described, and the majority of these lead to dominant-negative effects. However, the complete genotypic spectrum of desminopathy is not well established. Case presentation: Next-generation sequencing was performed on 51 cardiac disease genes in a proband with profound skeletal myopathy, dilated cardiomyopathy, and respiratory dysfunction. Our analyses revealed compound heterozygous DES variants, both of which are predicted to lead to a loss-of-function. Consistent with recessive inheritance, each variant was identified in an unaffected parent. Conclusions: This case report serves to broaden the variant spectrum of desminopathies and provides insight into the molecular mechanisms of desminopathy, supporting distinct dominant-negative and loss-of-function etiologies

Precision measurement of the neutron β-decay asymmetry

A new measurement of the neutron β-decay asymmetry A_0 has been carried out by the UCNA Collaboration using polarized ultracold neutrons (UCNs) from the solid deuterium UCN source at the Los Alamos Neutron Science Center. Improvements in the experiment have led to reductions in both statistical and systematic uncertainties leading to A_0=−0.11954(55)_(stat)(98)_(syst), corresponding to the ratio of axial-vector to vector coupling λ ≡ g_A/g_V = −1.2756(30)

The pressure-volume-temperature relationship of cellulose

Pressure–volume–temperature (PVT) mea- surements of a-cellulose with different water contents, were performed at temperatures from 25 to 180 °C and pressures from 19.6 to 196 MPa. PVT measurements allowed observation of the combined effects of pressure and temperature on the specific volume during cellulose thermo-compression. All isobars showed a decrease in cellulose specific volume with temperature. This densification is associated with a transition process of the cellulose, occurring at a temperature defined by the inflection point Tt of the isobar curve. Tt decreases from 110 to 40 °C with pressure and is lower as moisture content increases. For isobars obtained at high pressures and high moisture contents, after attaining a minimum, an increase in volume is observed with temperature that may be related to free water evaporation. PVT a-cellulose experimental data was compared with predicted values from a regression analysis of the Tait equations of state, usually applied to synthetic polymers. Good correla- tions were observed at low temperatures and low pressures. The densification observed from the PVT experimental data, at a temperature that decreases with pressure, could result from a sintering phenomenon, but more research is needed to actually understand the cohesion mechanism under these conditions

First direct constraints on Fierz interference in free-neutron β decay

Precision measurements of free-neutron β decay have been used to precisely constrain our understanding of the weak interaction. However, the neutron Fierz interference term b_n, which is particularly sensitive to beyond-standard-model tensor currents at the TeV scale, has thus far eluded measurement. Here we report the first direct constraints on this term, finding b_n=0.067±0.005_(stat)^(+0.090)_(−0.061)_(sys), consistent with the standard model. The uncertainty is dominated by absolute energy reconstruction and the linearity of the β spectrometer energy response

Urban informality and confinement: toward a relational framework

In the 21st century, a growing number of people live ‘informal’ lives within fissures between legality and informality. Concomitantly, power relations are increasingly expressed through devices of confinement. While urban informality and confinement are on the rise often occurring simultaneously, scholars have so far studied them separately. By contrast, this article proposes a new framework for analysing urban informality and confinement relationally. It generates new insights into the role of informality in the (re)production of confinement and, vice versa, the role of confinement in shaping informal practices. While these insights are valuable for urban studies in general, the article charts new lines of research on urban marginality. It also discusses how the six articles included in this special issue signal the heuristic potential of this relational framework by empirically examining distinct urban configurations of ‘confined informalities’ and ‘informal confinements’ across the Global North and the Global South

MeV-mass dark matter and primordial nucleosynthesis

The annihilation of new dark matter candidates with masses $m_X$ in the MeV range may account for the galactic positrons that are required to explain the 511 keV $\gamma$-ray flux from the galactic bulge. We study the impact of MeV-mass thermal relic particles on the primordial synthesis of $^2$H, $^4$He, and $^7$Li. If the new particles are in thermal equilibrium with neutrinos during the nucleosynthesis epoch they increase the helium mass fraction for m_X\alt 10 MeV and are thus disfavored. If they couple primarily to the electromagnetic plasma they can have the opposite effect of lowering both helium and deuterium. For $m_X=4$--10 MeV they can even improve the overall agreement between the predicted and observed $^2$H and $^4$He abundances.Comment: 11 pages, 10 figures, references and two appendices added, conclusions unchanged; accepted for publication in Phys.Rev.

Phenotype variability of infantile-onset multisystem neurologic, endocrine, and pancreatic disease IMNEPD

Infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD) has been recently linked to biallelic mutation of the peptidyl-tRNA hydrolase 2 gene PTRH2. Two index patients with IMNEPD in the original report had multiple neurological symptoms such as postnatal microcephaly, intellectual disability, developmental delay, sensorineural deafness, cerebellar atrophy, ataxia, and peripheral neuropathy. In addition, distal muscle weakness and abnormalities of thyroid, pancreas, and liver were found. Here, we report five further IMNEPD patients with a different homozygous PTRH2 mutation, broaden the phenotypic spectrum of the disease and differentiate common symptoms and interindividual variability in IMNEPD associated with a unique mutation. We thereby hope to better define IMNEPD and promote recognition and diagnosis of this novel disease entity

Search for neutron dark decay: n → χ + e⁺e⁻

In January, 2018, Fornal and Grinstein proposed that a previously unobserved neutron decay branch to a dark matter particle (χ) could account for the discrepancy in the neutron lifetime observed in two different types of experiments. One of the possible final states discussed includes a single χ along with an e⁺e⁻ pair. We use data from the UCNA (Ultracold Neutron Asymmetry) experiment to set limits on this decay channel. Coincident electron-like events are detected with ∼ 4π acceptance using a pair of detectors that observe a volume of stored Ultracold Neutrons (UCNs). We use the timing information of coincidence events to select candidate dark sector particle decays by applying a timing calibration and selecting events within a physically-forbidden timing region for conventional n → p + e⁻ + ν̅_e decays. The summed kinetic energy (E_(e⁺e⁻)) from such events is reconstructed and used to set limits, as a function of the χ mass, on the branching fraction for this decay channel

New result for the neutron β-asymmetry parameter A_0 from UCNA

Background: The neutron β-decay asymmetry parameter A_0 defines the angular correlation between the spin of the neutron and the momentum of the emitted electron. Values for A_0 permit an extraction of the ratio of the weak axial-vector to vector coupling constants, λ≡gA/gV, which under assumption of the conserved vector current hypothesis (gV=1) determines gA. Precise values for gA are important as a benchmark for lattice QCD calculations and as a test of the standard model. Purpose: The UCNA experiment, carried out at the Ultracold Neutron (UCN) source at the Los Alamos Neutron Science Center, was the first measurement of any neutron β-decay angular correlation performed with UCN. This article reports the most precise result for A_0 obtained to date from the UCNA experiment, as a result of higher statistics and reduced key systematic uncertainties, including from the neutron polarization and the characterization of the electron detector response. Methods: UCN produced via the downscattering of moderated spallation neutrons in a solid deuterium crystal were polarized via transport through a 7 T polarizing magnet and a spin flipper, which permitted selection of either spin state. The UCN were then contained within a 3-m long cylindrical decay volume, situated along the central axis of a superconducting 1 T solenoidal spectrometer. With the neutron spins then oriented parallel or anti-parallel to the solenoidal field, an asymmetry in the numbers of emitted decay electrons detected in two electron detector packages located on both ends of the spectrometer permitted an extraction of A_0. Results: The UCNA experiment reports a new 0.67% precision result for A_0 of A_0=−0.12054(44)_(stat)(68)_(syst), which yields λ=gA/gV=−1.2783(22). Combination with the previous UCNA result and accounting for correlated systematic uncertainties produces A0=−0.12015(34)stat(63)syst and λ=gA/gV=−1.2772(20). Conclusions: This new result for A0 and gA/gV from the UCNA experiment has provided confirmation of the shift in values for gA/gV that has emerged in the published results from more recent experiments, which are in striking disagreement with the results from older experiments. Individual systematic corrections to the asymmetries in older experiments (published prior to 2002) were >10%, whereas those in the more recent ones (published after 2002) have been of the scale of <2%. The impact of these older results on the global average will be minimized should future measurements of A0 reach the 0.1% level of precision with central values near the most recent results