Elastic p-3He and n-3H scattering with two- and three-body forces

We report on a microscopic calculation of n-3H and p-3He scattering employing the Argonne v_{18} and v_8' nucleon-nucleon potentials with and without additional three-nucleon force. An R-matrix analysis of the p-3He and n-3H scattering data is presented. Comparisons are made for the phase shifts and a selection of measurements in both scattering systems. Differences between our calculation and the R-matrix results or the experimental data can be attributed to only two partial waves (3P0 and 3P2). We find the effect of the Urbana IX and the Texas-Los Alamos three-nucleon forces on the phase shifts to be negligible.Comment: submitted to Phys. Rev.

PDGFA-associated protein 1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification

The establishment of protective humoral immunity is dependent on the ability of mature B cells to undergo antibody gene diversification while adjusting to the physiological stressors induced by activation with the antigen. Mature B cells diversify their antibody genes by class switch recombination (CSR) and somatic hypermutation (SHM), which are both dependent on efficient induction of activation-induced cytidine deaminase (AID). Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation and ensures efficient antibody diversification by promoting their survival and optimal function

Thermodynamics of pyrope-majorite, Mg3Al2Si3O12-Mg4Si4O12, solid solution from atomistic model calculations

Static lattice energy calculations, based on empirical pair potentials have been performed for a large set of different structures with compositions between pyrope and majorite, and with different states of order of octahedral cations. The energies have been cluster expanded using pair and quaternary terms. The derived ordering constants have been used to constrain Monte Carlo simulations of temperature-dependent properties in the ranges of 1073 3673K and 0 20 GPa. The free energies of mixing have been calculated using the method of thermodynamic integration. At zero pressure the cubic/tetragonal transition is predicted for pure majorite at 3300 K. The transition temperature decreases with the increase of the pyrope mole fraction. A miscibility gap associated with the transition starts to develop at about 2000K and xmaj 0.8, and widens with the decrease in temperature and the increase in pressure. Activity composition relations in the range of 0 20 GPa and 1073 2673K are described with the help of a high-order Redlich Kister polynomial

Lagomorpha as a model morphological system

Due to their global distribution, invasive history, and unique characteristics, European rabbits are recognizable almost anywhere on our planet. Although they are members of a much larger group of living and extinct mammals [Mammalia, Lagomorpha (rabbits, hares, and pikas)], the group is often characterized by several well-known genera (e.g., Oryctolagus, Sylvilagus, Lepus, and Ochotona). This representation does not capture the extraordinary diversity of behavior and form found throughout the order. Model organisms are commonly used as exemplars for biological research, but there are a limited number of model clades or lineages that have been used to study evolutionary morphology in a more explicitly comparative way. We present this review paper to show that lagomorphs are a strong system in which to study macro- and micro-scale patterns of morphological change within a clade that offers underappreciated levels of diversity. To this end, we offer a summary of the status of relevant aspects of lagomorph biology.Brian Kraatz, Rafik Belabbas, Łucja Fostowicz-Frelik, De-Yan Ge, Alexander N. Kuznetsov, Madlen M. Lang ... et al

Pdap1 protects mature B lymphocytes from stress-induced cell death and promotes antibody gene diversification

The establishment of protective humoral immunity is dependent on the ability of mature B cells to undergo antibody gene diversification while adjusting to the physiological stressors induced by activation with the antigen. Mature B cells diversify their antibody genes by class switch recombination (CSR) and somatic hypermutation (SHM), which are both dependent on efficient induction of activation-induced cytidine deaminase (AID). Here, we identified PDGFA-associated protein 1 (Pdap1) as an essential regulator of cellular homeostasis in mature B cells. Pdap1 deficiency leads to sustained expression of the integrated stress response (ISR) effector activating transcription factor 4 (Atf4) and induction of the ISR transcriptional program, increased cell death, and defective AID expression. As a consequence, loss of Pdap1 reduces germinal center B cell formation and impairs CSR and SHM. Thus, Pdap1 protects mature B cells against chronic ISR activation and ensures efficient antibody diversification by promoting their survival and optimal function

A Multitrait Locus Regulates Sarbecovirus Pathogenesis

Infectious diseases have shaped the human population genetic structure, and genetic variation influences the susceptibility to many viral diseases. However, a variety of challenges have made the implementation of traditional human Genomewide Association Studies (GWAS) approaches to study these infectious outcomes challenging. In contrast, mouse models of infectious diseases provide an experimental control and precision, which facilitates analyses and mechanistic studies of the role of genetic variation on infection. Here we use a genetic mapping cross between two distinct Collaborative Cross mouse strains with respect to severe acute respiratory syndrome coronavirus (SARS-CoV) disease outcomes. We find several loci control differential disease outcome for a variety of traits in the context of SARS-CoV infection. Importantly, we identify a locus on mouse chromosome 9 that shows conserved synteny with a human GWAS locus for SARS-CoV-2 severe disease. We follow-up and confirm a role for this locus, and identify two candidate genes, CCR9 and CXCR6, that both play a key role in regulating the severity of SARS-CoV, SARS-CoV-2, and a distantly related bat sarbecovirus disease outcomes. As such we provide a template for using experimental mouse crosses to identify and characterize multitrait loci that regulate pathogenic infectious outcomes across species. IMPORTANCE Host genetic variation is an important determinant that predicts disease outcomes following infection. In the setting of highly pathogenic coronavirus infections genetic determinants underlying host susceptibility and mortality remain unclear. To elucidate the role of host genetic variation on sarbecovirus pathogenesis and disease outcomes, we utilized the Collaborative Cross (CC) mouse genetic reference population as a model to identify susceptibility alleles to SARS-CoV and SARS-CoV-2 infections. Our findings reveal that a multitrait loci found in chromosome 9 is an important regulator of sarbecovirus pathogenesis in mice. Within this locus, we identified and validated CCR9 and CXCR6 as important regulators of host disease outcomes. Specifically, both CCR9 and CXCR6 are protective against severe SARS-CoV, SARS-CoV-2, and SARS-related HKU3 virus disease in mice. This chromosome 9 multitrait locus may be important to help identify genes that regulate coronavirus disease outcomes in humans

Lasers and optics: Looking towards third generation gravitational wave detectors

Third generation terrestrial interferometric gravitational wave detectors will likely require significant advances in laser and optical technologies to reduce two of the main limiting noise sources: thermal noise due to mirror coatings and quantum noise arising from a combination of shot noise and radiation pressure noise. Increases in laser power and possible changes of the operational wavelength require new high power laser sources and new electro-optic modulators and Faraday isolators. Squeezed light can be used to further reduce the quantum noise while nano-structured optical components can be used to reduce or eliminate mirror coating thermal noise as well as to implement all-reflective interferometer configurations to avoid thermal effects in mirror substrates. This paper is intended to give an overview on the current state-of-the-art and future trends in these areas of ongoing research and development.NSF/PHY0555453NSF/PHY0757968NSF/PHY0653582DFG/SFB/407DFG/SFB/TR7DFG/EXC/QUES

Effect of allopurinol in addition to hypothermia treatment in neonates for hypoxic-ischemic brain injury on neurocognitive outcome (ALBINO): Study protocol of a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III)

Background: Perinatal asphyxia and resulting hypoxic-ischemic encephalopathy is a major cause of death and long-term disability in term born neonates. Up to 20,000 infants each year are affected by HIE in Europe and even more in regions with lower level of perinatal care. The only established therapy to improve outcome in these infants is therapeutic hypothermia. Allopurinol is a xanthine oxidase inhibitor that reduces the production of oxygen radicals as superoxide, which contributes to secondary energy failure and apoptosis in neurons and glial cells after reperfusion of hypoxic brain tissue and may further improve outcome if administered in addition to therapeutic hypothermia. Methods: This study on the effects of ALlopurinol in addition to hypothermia treatment for hypoxic-ischemic Brain Injury on Neurocognitive Outcome (ALBINO), is a European double-blinded randomized placebo-controlled parallel group multicenter trial (Phase III) to evaluate the effect of postnatal allopurinol administered in addition to standard of care (including therapeutic hypothermia if indicated) on the incidence of death and severe neurodevelopmental impairment at 24 months of age in newborns with perinatal hypoxic-ischemic insult and signs of potentially evolving encephalopathy. Allopurinol or placebo will be given in addition to therapeutic hypothermia (where indicated) to infants with a gestational age 65 36 weeks and a birth weight 65 2500 g, with severe perinatal asphyxia and potentially evolving encephalopathy. The primary endpoint of this study will be death or severe neurodevelopmental impairment versus survival without severe neurodevelopmental impairment at the age of two years. Effects on brain injury by magnetic resonance imaging and cerebral ultrasound, electric brain activity, concentrations of peroxidation products and S100B, will also be studied along with effects on heart function and pharmacokinetics of allopurinol after iv-infusion. Discussion: This trial will provide data to assess the efficacy and safety of early postnatal allopurinol in term infants with evolving hypoxic-ischemic encephalopathy. If proven efficacious and safe, allopurinol could become part of a neuroprotective pharmacological treatment strategy in addition to therapeutic hypothermia in children with perinatal asphyxia. Trial registration: NCT03162653, www.ClinicalTrials.gov, May 22, 2017

Energetic particle influence on the Earth's atmosphere

This manuscript gives an up-to-date and comprehensive overview of the effects of energetic particle precipitation (EPP) onto the whole atmosphere, from the lower thermosphere/mesosphere through the stratosphere and troposphere, to the surface. The paper summarizes the different sources and energies of particles, principally galactic cosmic rays (GCRs), solar energetic particles (SEPs) and energetic electron precipitation (EEP). All the proposed mechanisms by which EPP can affect the atmosphere are discussed, including chemical changes in the upper atmosphere and lower thermosphere, chemistry-dynamics feedbacks, the global electric circuit and cloud formation. The role of energetic particles in Earth’s atmosphere is a multi-disciplinary problem that requires expertise from a range of scientific backgrounds. To assist with this synergy, summary tables are provided, which are intended to evaluate the level of current knowledge of the effects of energetic particles on processes in the entire atmosphere