Reaction-controlled diffusion: Monte Carlo simulations

We study the coupled two-species non-equilibrium reaction-controlled diffusion model introduced by Trimper et al. [Phys. Rev. E 62, 6071 (2000)] by means of detailed Monte Carlo simulations in one and two dimensions. Particles of type A may independently hop to an adjacent lattice site provided it is occupied by at least one B particle. The B particle species undergoes diffusion-limited reactions. In an active state with nonzero, essentially homogeneous B particle saturation density, the A species displays normal diffusion. In an inactive, absorbing phase with exponentially decaying B density, the A particles become localized. In situations with algebraic decay rho_B(t) ~ t^{-alpha_B}, as occuring either at a non-equilibrium continuous phase transition separating active and absorbing states, or in a power-law inactive phase, the A particles propagate subdiffusively with mean-square displacement ~ t^{1-alpha_A}. We find that within the accuracy of our simulation data, \alpha_A = \alpha_B as predicted by a simple mean-field approach. This remains true even in the presence of strong spatio-temporal fluctuations of the B density. However, in contrast with the mean-field results, our data yield a distinctly non-Gaussian A particle displacement distribution n_A(x,t) that obeys dynamic scaling and looks remarkably similar for the different processes investigated here. Fluctuations of effective diffusion rates cause a marked enhancement of n_A(x,t) at low displacements |x|, indicating a considerable fraction of practically localized A particles, as well as at large traversed distances.Comment: Revtex, 19 pages, 27 eps figures include

Constraining mean-field models of the nuclear matter equation of state at low densities

An extension of the generalized relativistic mean-field (gRMF) model with density dependent couplings is introduced in order to describe thermodynamical properties and the composition of dense nuclear matter for astrophysical applications. Bound states of light nuclei and two-nucleon scattering correlations are considered as explicit degrees of freedom in the thermodynamical potential. They are represented by quasiparticles with medium-dependent properties. The model describes the correct low-density limit given by the virial equation of state (VEoS) and reproduces RMF results around nuclear saturation density where clusters are dissolved. A comparison between the fugacity expansions of the VEoS and the gRMF model provides consistency relations between the quasiparticles properties, the nucleon-nucleon scattering phase shifts and the meson-nucleon couplings of the gRMF model at zero density. Relativistic effects are found to be important at temperatures that are typical in astrophysical applications. Neutron matter and symmetric matter are studied in detail.Comment: 50 pages, 21 figure

Support for Aboriginal health services in reducing harms from alcohol : 2-year service provision outcomes in a cluster randomized trial

Background and aims There is a higher prevalence of unhealthy alcohol use among Indigenous populations, but there have been few studies of the effectiveness of screening and treatment in primary health care. Over 24 months, we tested whether a model of service-wide support could increase screening and any alcohol treatment. Design Cluster-randomized trial with 24-month implementation (12 months active, 12 months maintenance). Setting Australian Aboriginal Community Controlled primary care services. Participants Twenty-two services (83 032 clients) that use Communicare practice software and see at least 1000 clients annually, randomized to the treatment arm or control arm. Intervention and comparator Multi-faceted early support model versus a comparator of waiting-list control (11 services). Measurements A record (presence = 1, absence = 0) of: (i) Alcohol Use Disorders Identification Test—Consumption (AUDIT-C) screening (primary outcome), (ii) any-treatment and (iii) brief intervention. We received routinely collected practice data bimonthly over 3 years (1-year baseline, 1-year implementation, 1-year maintenance). Multi-level logistic modelling was used to compare the odds of each outcome before and after implementation. Findings The odds of being screened within any 2-month reference period increased in both arms post-implementation, but the increase was nearly eight times greater in early-support services [odds ratio (OR) = 7.95, 95% confidence interval (CI) = 4.04–15.63, P < 0.001]. The change in odds of any treatment in early support was nearly double that of waiting-list controls (OR = 1.89, 95% CI = 1.19–2.98, P = 0.01) but was largely driven by decrease in controls. There was no clear evidence of difference between groups in the change in the odds of provision of brief intervention (OR = 1.95, 95% CI = 0.53–7.17, P = 0.32). Conclusions An early support model designed to aid routine implementation of alcohol screening and treatment in Aboriginal health services resulted in improvement of Alcohol Use Disorders Identification Test—Consumption screening rates over 24 months of implementation, but the effect on treatment was less clear

Supporting Aboriginal Community Controlled Health Services to deliver alcohol care : Protocol for a cluster randomised controlled trial

Introduction Indigenous peoples who have experienced colonisation or oppression can have a higher prevalence of alcohol-related harms. In Australia, Aboriginal Community Controlled Health Services (ACCHSs) offer culturally accessible care to Aboriginal and Torres Strait Islander (Indigenous) peoples. However there are many competing health, socioeconomic and cultural client needs. Methods and analysis A randomised cluster wait-control trial will test the effectiveness of a model of tailored and collaborative support for ACCHSs in increasing use of alcohol screening (with Alcohol Use Disorders Identification Test-Consumption (AUDIT-C)) and of treatment provision (brief intervention, counselling or relapse prevention medicines). Setting Twenty-two ACCHSs across Australia. Randomisation Services will be stratified by remoteness, then randomised into two groups. Half receive support soon after the trial starts (intervention or ‘early support’); half receive support 2 years later (wait-control or ‘late support’). The support Core support elements will be tailored to local needs and include: support to nominate two staff as champions for increasing alcohol care; a national training workshop and bimonthly teleconferences for service champions to share knowledge; onsite training, and bimonthly feedback on routinely collected data on screening and treatment provision. Outcomes and analysis Primary outcome is use of screening using AUDIT-C as routinely recorded on practice software. Secondary outcomes are recording of brief intervention, counselling, relapse prevention medicines; and blood pressure, gamma glutamyltransferase and HbA1c. Multi-level logistic regression will be used to test the effectiveness of support. Ethics and dissemination Ethical approval has been obtained from eight ethics committees: the Aboriginal Health and Medical Research Council of New South Wales (1217/16); Central Australian Human Research Ethics Committee (CA-17-2842); Northern Territory Department of Health and Menzies School of Health Research (2017-2737); Central Queensland Hospital and Health Service (17/QCQ/9); Far North Queensland (17/QCH/45-1143); Aboriginal Health Research Ethics Committee, South Australia (04-16-694); St Vincent’s Hospital (Melbourne) Human Research Ethics Committee (LRR 036/17); and Western Australian Aboriginal Health Ethics Committee (779). Trial registration number ACTRN12618001892202; Pre-results

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Peer reviewedPublisher PD

KAP-1 promotes resection of broken DNA ends not protected by γ-H2AX and 53BP1 in G1-phase lymphocytes

The resection of broken DNA ends is required for DNA double-strand break (DSB) repair by homologous recombination (HR) but can inhibit normal repair by nonhomologous end joining (NHEJ), the main DSB repair pathway in G(1)-phase cells. Antigen receptor gene assembly proceeds through DNA DSB intermediates generated in G(1)-phase lymphocytes by the RAG endonuclease. These DSBs activate ATM, which phosphorylates H2AX, forming γ-H2AX in flanking chromatin. γ-H2AX prevents CtIP from initiating resection of RAG DSBs. Whether there are additional proteins required to promote resection of these DNA ends is not known. KRAB-associated protein 1 (KAP-1) (TRIM28) is a transcriptional repressor that modulates chromatin structure and has been implicated in the repair of DNA DSBs in heterochromatin. Here, we show that in murine G(1)-phase lymphocytes, KAP-1 promotes resection of DSBs that are not protected by H2AX and its downstream effector 53BP1. In these murine cells, KAP-1 activity in DNA end resection is attenuated by a single-amino-acid change that reflects a KAP-1 polymorphism between primates and other mammalian species. These findings establish KAP-1 as a component of the machinery that can resect DNA ends in G(1)-phase cells and suggest that there may be species-specific features to this activity

Ionization degree of the electron-hole plasma in semiconductor quantum wells

The degree of ionization of a nondegenerate two-dimensional electron-hole plasma is calculated using the modified law of mass action, which takes into account all bound and unbound states in a screened Coulomb potential. Application of the variable phase method to this potential allows us to treat scattering and bound states on the same footing. Inclusion of the scattering states leads to a strong deviation from the standard law of mass action. A qualitative difference between mid- and wide-gap semiconductors is demonstrated. For wide-gap semiconductors at room temperature, when the bare exciton binding energy is of the order of T, the equilibrium consists of an almost equal mixture of correlated electron-hole pairs and uncorrelated free carriers.Comment: 22 pages, 6 figure

Stretching the Rules: Monocentric Chromosomes with Multiple Centromere Domains

The centromere is a functional chromosome domain that is essential for faithful chromosome segregation during cell division and that can be reliably identified by the presence of the centromere-specific histone H3 variant CenH3. In monocentric chromosomes, the centromere is characterized by a single CenH3-containing region within a morphologically distinct primary constriction. This region usually spans up to a few Mbp composed mainly of centromere-specific satellite DNA common to all chromosomes of a given species. In holocentric chromosomes, there is no primary constriction; the centromere is composed of many CenH3 loci distributed along the entire length of a chromosome. Using correlative fluorescence light microscopy and high-resolution electron microscopy, we show that pea (Pisum sativum) chromosomes exhibit remarkably long primary constrictions that contain 3-5 explicit CenH3-containing regions, a novelty in centromere organization. In addition, we estimate that the size of the chromosome segment delimited by two outermost domains varies between 69 Mbp and 107 Mbp, several factors larger than any known centromere length. These domains are almost entirely composed of repetitive DNA sequences belonging to 13 distinct families of satellite DNA and one family of centromeric retrotransposons, all of which are unevenly distributed among pea chromosomes. We present the centromeres of Pisum as novel ``meta-polycentric'' functional domains. Our results demonstrate that the organization and DNA composition of functional centromere domains can be far more complex than previously thought, do not require single repetitive elements, and do not require single centromere domains in order to segregate properly. Based on these findings, we propose Pisum as a useful model for investigation of centromere architecture and the still poorly understood role of repetitive DNA in centromere evolution, determination, and function

Sources of non-methane hydrocarbons in surface air in Delhi, India

Rapid economic growth and development have exacerbated air quality problems across India, driven by many poorly understood pollution sources and understanding their relative importance remains critical to characterising the key drivers of air pollution. A comprehensive suite of measurements of 90 non-methane hydrocarbons (NMHCs) (C2–C14), including 12 speciated monoterpenes and higher molecular weight monoaromatics, were made at an urban site in Old Delhi during the pre-monsoon (28-May to 05-Jun 2018) and post-monsoon (11 to 27-Oct 2018) seasons using dual-channel gas chromatography (DC-GC-FID) and two-dimensional gas chromatography (GC×GC-FID). Significantly higher mixing ratios of NMHCs were measured during the post-monsoon campaign, with a mean night-time enhancement of around 6. Like with NOx and CO, strong diurnal profiles were observed for all NMHCs, except isoprene, with very high NMHC mixing ratios between 35–1485 ppbv. The sum of mixing ratios of benzene, toluene, ethylbenzene and xylenes (BTEX) routinely exceeded 100 ppbv at night during the post-monsoon period, with a maximum measured mixing ratio of monoaromatic species of 370 ppbv. The mixing ratio of highly reactive monoterpenes peaked at around 6 ppbv in the post-monsoon campaign and correlated strongly with anthropogenic NMHCs, suggesting a strong non-biogenic source in Delhi. A detailed source apportionment study was conducted which included regression analysis to CO, acetylene and other NMHCs, hierarchical cluster analysis, EPA UNMIX 6.0, principal component analysis/absolute principal component scores (PCA/APCS) and comparison with NMHC ratios (benzene/toluene and i-/n-pentane) in ambient samples to liquid and solid fuels. These analyses suggested the primary source of anthropogenic NMHCs in Delhi was from traffic emissions (petrol and diesel), with average mixing ratio contributions from Unmix and PCA/APCS models of 38% from petrol, 14% from diesel and 32% from liquified petroleum gas (LPG) with a smaller contribution (16%) from solid fuel combustion. Detailed consideration of the underlying meteorology during the campaigns showed that the extreme night-time mixing ratios of NMHCs during the post-monsoon campaign were the result of emissions into a very shallow and stagnant boundary layer. The results of this study suggest that despite widespread open burning in India, traffic-related petrol and diesel emissions remain the key drivers of gas-phase urban air pollution in Delhi

Accelerating drug discovery for Alzheimer's disease: best practices for preclinical animal studies

Animal models have contributed significantly to our understanding of the underlying biological mechanisms of Alzheimer's disease (AD). As a result, over 300 interventions have been investigated and reported to mitigate pathological phenotypes or improve behavior in AD animal models or both. To date, however, very few of these findings have resulted in target validation in humans or successful translation to disease-modifying therapies. Challenges in translating preclinical studies to clinical trials include the inability of animal models to recapitulate the human disease, variations in breeding and colony maintenance, lack of standards in design, conduct and analysis of animal trials, and publication bias due to under-reporting of negative results in the scientific literature. The quality of animal model research on novel therapeutics can be improved by bringing the rigor of human clinical trials to animal studies. Research communities in several disease areas have developed recommendations for the conduct and reporting of preclinical studies in order to increase their validity, reproducibility, and predictive value. To address these issues in the AD community, the Alzheimer's Drug Discovery Foundation partnered with Charles River Discovery Services (Morrisville, NC, USA) and Cerebricon Ltd. (Kuopio, Finland) to convene an expert advisory panel of academic, industry, and government scientists to make recommendations on best practices for animal studies testing investigational AD therapies. The panel produced recommendations regarding the measurement, analysis, and reporting of relevant AD targets, th choice of animal model, quality control measures for breeding and colony maintenance, and preclinical animal study design. Major considerations to incorporate into preclinical study design include a priori hypotheses, pharmacokinetics-pharmacodynamics studies prior to proof-of-concept testing, biomarker measurements, sample size determination, and power analysis. The panel also recommended distinguishing between pilot 'exploratory' animal studies and more extensive 'therapeutic' studies to guide interpretation. Finally, the panel proposed infrastructure and resource development, such as the establishment of a public data repository in which both positive animal studies and negative ones could be reported. By promoting best practices, these recommendations can improve the methodological quality and predictive value of AD animal studies and make the translation to human clinical trials more efficient and reliable