Skeletal muscle ATP turnover by 31P magnetic resonance spectroscopy during moderate and heavy bilateral knee-extension

During constant-power high-intensity exercise, the expected increase in oxygen uptake (V̇O2) is supplemented by a V̇O2 slow component (V̇O2 sc ), reflecting reduced work efficiency, predominantly within the locomotor muscles. The intracellular source of inefficiency is postulated to be an increase in the ATP cost of power production (an increase in P/W). To test this hypothesis, we measured intramuscular ATP turnover with (31)P magnetic resonance spectroscopy (MRS) and whole-body V̇O2 during moderate (MOD) and heavy (HVY) bilateral knee-extension exercise in healthy participants (n = 14). Unlocalized (31)P spectra were collected from the quadriceps throughout using a dual-tuned ((1)H and (31)P) surface coil with a simple pulse-and-acquire sequence. Total ATP turnover rate (ATPtot) was estimated at exercise cessation from direct measurements of the dynamics of phosphocreatine (PCr) and proton handling. Between 3 and 8 min during MOD, there was no discernable V̇O2 sc (mean ± SD, 0.06 ± 0.12 l min(-1)) or change in [PCr] (30 ± 8 vs. 32 ± 7 mm) or ATPtot (24 ± 14 vs. 17 ± 14 mm min(-1); each P = n.s.). During HVY, the V̇O2 sc was 0.37 ± 0.16 l min(-1) (22 ± 8%), [PCr] decreased (19 ± 7 vs. 18 ± 7 mm, or 12 ± 15%; P < 0.05) and ATPtot increased (38 ± 16 vs. 44 ± 14 mm min(-1), or 26 ± 30%; P < 0.05) between 3 and 8 min. However, the increase in ATPtot (ΔATPtot) was not correlated with the V̇O2 sc during HVY (r(2) = 0.06; P = n.s.). This lack of relationship between ΔATPtot and V̇O2 sc , together with a steepening of the [PCr]-V̇O2 relationship in HVY, suggests that reduced work efficiency during heavy exercise arises from both contractile (P/W) and mitochondrial sources (the O2 cost of ATP resynthesis; P/O)

Charged Particle Pseudorapidity Distributions in Au+Al, Cu, Au, and U Collisions at 10.8 A⋅\cdotGeV/c

We present the results of an analysis of charged particle pseudorapidity distributions in the central region in collisions of a Au projectile with Al, Cu, Au, and U targets at an incident energy of 10.8~GeV/c per nucleon. The pseudorapidity distributions are presented as a function of transverse energy produced in the target or central pseudorapidity regions. The correlation between charged multiplicity and transverse energy measured in the central region, as well as the target and projectile regions is also presented. We give results for transverse energy per charged particle as a function of pseudorapidity and centrality.Comment: 31 pages + 12 figures (compressed and uuencoded by uufiles), LATEX, Submitted to PR

Proton and Pion Production Relative to the Reaction Plane in Au + Au Collisions at AGS Energies

Results are presented of an analysis of proton and charged pion azimuthal distributions measured with respect to the reaction plane in Au + Au collisions at a beam momentum of about 11 AGeV/c. The azimuthal anisotropy is studied as a function of particle rapidity and transverse momentum for different centralities of the collisions. The triple differential (in rapidity, transverse momentum, and azimuthal angle) distributions are reconstructed. A comparison of the results with a previous analysis of charged particle and transverse energy flow as well as with model predictions is presented.Comment: 23 pages (LaTeX), 12 figure

Proton and Pion Production in Au+Au Collisions at 10.8A GeV/c

We present proton and pion tranverse momentum spectra and rapidity distributions for Au+Au collisions at 10.8A GeV/c. The proton spectra exhibit collective transverse flow effects. Evidence of the influence of the Coulomb interaction from the fireball is found in the pion transverse momentum spectra. The data are compared with the predictions of the RQMD event generator.Comment: plain tex (revtex), 24 pages Submitted to Phys. Rev.

Modular Design via Multiple Anion Chemistry of the High Mobility van der Waals Semiconductor Bi₄O₄SeCl₂

Making new van der Waals materials with electronic or magnetic functionality is a chemical design challenge for the development of two-dimensional nanoelectronic and energy conversion devices. We present the synthesis and properties of the van der Waals material Bi4O4SeCl2, which is a 1:1 superlattice of the structural units present in the van der Waals insulator BiOCl and the three-dimensionally connected semiconductor Bi2O2Se. The presence of three anions gives the new structure both the bridging selenide anion sites that connect pairs of Bi2O2 layers in Bi2O2Se and the terminal chloride sites that produce the van der Waals gap in BiOCl. This retains the electronic properties of Bi2O2Se while reducing the dimensionality of the bonding network connecting the Bi2O2Se units to allow exfoliation of Bi4O4SeCl2 to 1.4 nm height. The superlattice structure is stabilized by the configurational entropy of anion disorder across the terminal and bridging sites. The reduction in connective dimensionality with retention of electronic functionality stems from the expanded anion compositional diversity

COVID-19: protocol for observational studies utilizing near real-time electronic Australian general practice data to promote effective care and best-practice policy—a design thinking approach

Background: Health systems around the world have been forced to make choices about how to prioritize care, manage infection control and maintain reserve capacity for future disease outbreaks. Primary healthcare has moved into the front line as COVID-19 testing transitions from hospitals to multiple providers, where tracking testing behaviours can be fragmented and delayed. Pooled general practice data are a valuable resource which can be used to inform population and individual care decision-making. This project aims to examine the feasibility of using near real-time electronic general practice data to promote effective care and best-practice policy. Methods: The project will utilize a design thinking approach involving all collaborators (primary health networks [PHNs], general practices, consumer groups, researchers, and digital health developers, pathology professionals) to enhance the development of meaningful and translational project outcomes. The project will be based on a series of observational studies utilizing near real-time electronic general practice data from a secure and comprehensive digital health platform [POpulation Level Analysis and Reporting (POLAR) general practice data warehouse]. The study will be carried out over 1.5 years (July 2020–December 2021) using data from over 450 general practices within three Victorian PHNs and Gippsland PHN, Eastern Melbourne PHN and South Eastern Melbourne PHN, supplemented by data from consenting general practices from two PHNs in New South Wales, Central and Eastern Sydney PHN and South Western Sydney PHN. Discussion: The project will be developed using a design thinking approach, leading to the building of a meaningful near real-time COVID-19 geospatial reporting framework and dashboard for decision-makers at community, state and nationwide levels, to identify and monitor emerging trends and the impact of interventions/policy decisions. This will integrate timely evidence about the impact of the COVID-19 pandemic related to its diagnosis and treatment, and its impact across clinical, population and general practice levels

Polycomb Binding Precedes Early-Life Stress Responsive DNA Methylation at the Avp Enhancer

Early-life stress (ELS) in mice causes sustained hypomethylation at the downstream Avp enhancer, subsequent overexpression of hypothalamic Avp and increased stress responsivity. The sequence of events leading to Avp enhancer methylation is presently unknown. Here, we used an embryonic stem cell-derived model of hypothalamic-like differentiation together with in vivo experiments to show that binding of polycomb complexes (PcG) preceded the emergence of ELS-responsive DNA methylation and correlated with gene silencing. At the same time, PcG occupancy associated with the presence of Tet proteins preventing DNA methylation. Early hypothalamic-like differentiation triggered PcG eviction, DNA-methyltransferase recruitment and enhancer methylation. Concurrently, binding of the Methyl-CpG-binding and repressor protein MeCP2 increased at the enhancer although Avp expression during later stages of differentiation and the perinatal period continued to increase. Overall, we provide evidence of a new role of PcG proteins in priming ELS-responsive DNA methylation at the Avp enhancer prior to epigenetic programming consistent with the idea that PcG proteins are part of a flexible silencing system during neuronal development

Two-Proton Correlations from 14.6A GeV/c Si+Pb and 11.5A GeV/c Au+Au Central Collisions

Two-proton correlation functions have been measured in Si+Pb collisions at 14.6A GeV/c and Au+Au collisions at 11.5A GeV/c by the E814/E877 collaboration. Data are compared with predictions of the transport model RQMD and the source size is inferred from this comparison. Our analysis shows that, for both reactions, the characteristic size of the system at freeze-out exceeds the size of the projectile, suggesting that the fireball created in the collision has expanded. For Au+Au reactions, the observed centrality dependence of the two-proton correlation function implies that more central collisions lead to a larger source sizes.Comment: RevTex, 12 pages, 5 figure

Keratin 12 missense mutation induces the unfolded protein response and apoptosis in meesmann epithelial corneal dystrophy

Meesmann epithelial corneal dystrophy (MECD) is a rare autosomal dominant disorder caused by dominant-negative mutations within the KRT3 or KRT12 genes, which encode the cytoskeletal protein keratins K3 and K12, respectively. To investigate the pathomechanism of this disease, we generated and phenotypically characterized a novel knock-in humanized mouse model carrying the severe, MECD-associated, K12-Leu132Pro mutation. Although no overt changes in corneal opacity were detected by slit-lamp examination, the corneas of homozygous mutant mice exhibited histological and ultrastructural epithelial cell fragility phenotypes. An altered keratin expression profile was observed in the cornea of mutant mice, confirmed by western blot, RNA-seq and quantitative real-time polymerase chain reaction. Mass spectrometry (MS) and immunohistochemistry demonstrated a similarly altered keratin profile in corneal tissue from a K12-Leu132Pro MECD patient. The K12-Leu132Pro mutation results in cytoplasmic keratin aggregates. RNA-seq analysis revealed increased chaperone gene expression, and apoptotic unfolded protein response (UPR) markers, CHOP and Caspase 12, were also increased in the MECD mice. Corneal epithelial cell apoptosis was increased 17-fold in the mutant cornea, compared with the wild-type (P &lt; 0.001). This elevation of UPR marker expression was also observed in the human MECD cornea. This is the first reporting of a mouse model for MECD that recapitulates the human disease and is a valuable resource in understanding the pathomechanism of the disease. Although the most severe phenotype is observed in the homozygous mice, this model will still provide a test-bed for therapies not only for corneal dystrophies but also for other keratinopathies caused by similar mutations