Polygenic Adaptation to an Environmental Shift: Temporal Dynamics of Variation Under Gaussian Stabilizing Selection and Additive Effects on a Single Trait.

Predictions about the effect of natural selection on patterns of linked neutral variation are largely based on models involving the rapid fixation of unconditionally beneficial mutations. However, when phenotypes adapt to a new optimum trait value, the strength of selection on individual mutations decreases as the population adapts. Here, I use explicit forward simulations of a single trait with additive-effect mutations adapting to an "optimum shift." Detectable "hitchhiking" patterns are only apparent if (i) the optimum shifts are large with respect to equilibrium variation for the trait, (ii) mutation rates to large-effect mutations are low, and (iii) large-effect mutations rapidly increase in frequency and eventually reach fixation, which typically occurs after the population reaches the new optimum. For the parameters simulated here, partial sweeps do not appreciably affect patterns of linked variation, even when the mutations are strongly selected. The contribution of new mutations vs. standing variation to fixation depends on the mutation rate affecting trait values. Given the fixation of a strongly selected variant, patterns of hitchhiking are similar on average for the two classes of sweeps because sweeps from standing variation involving large-effect mutations are rare when the optimum shifts. The distribution of effect sizes of new mutations has little effect on the time to reach the new optimum, but reducing the mutational variance increases the magnitude of hitchhiking patterns. In general, populations reach the new optimum prior to the completion of any sweeps, and the times to fixation are longer for this model than for standard models of directional selection. The long fixation times are due to a combination of declining selection pressures during adaptation and the possibility of interference among weakly selected sites for traits with high mutation rates

Discourse-pragmatic variation in Paris French and London English: Insights from general extenders

This paper examines the use of general extenders (GEs), such as and stuff in English and et tout in French, in Paris French and London English. We aim to compare the social and the linguistic conditioning of extender use in the two languages, discuss the different kinds of spread in the two cities and reflect on the specificity of discourse-pragmatic variation. The study shows that GE forms as well as frequencies vary across factors such as gender, age and ethnicity, while some variants also appear to be grammaticalising and acquiring new pragmatic functions. The analysis includes a comparison of different age groups, and finds that different types of generational change may be occurring in both languages. In London, forms such as and stuff and and that diverge along ethnic lines, whereas in Paris et tout is becoming the dominant variant across the board. While different variants in both languages are indirectly associated with different social categories, they perform similar pragmatic functions such as hedging, marking solidarity and appealing to common knowledge between the speaker and the interlocutor(s)

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

ObjectivesIn a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported.MethodsWe systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases.ResultsWe found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls.ConclusionsThe rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility

From Quantum Cheating to Quantum Security

For thousands of years, code-makers and code-breakers have been competing for supremacy. Their arsenals may soon include a powerful new weapon: quantum mechanics. We give an overview of quantum cryptology as of November 2000.Comment: 14 pages, 4 figures. Originally appeared in Physics Today: . This article may be downloaded for personal use only. Any other use requires prior permission of both the author and the American Institute of Physic

Individual differences in the neuropsychopathology of addiction.

Drug addiction or substance-use disorder is a chronically relapsing disorder that progresses through binge/intoxication, withdrawal/negative affect and preoccupation/anticipation stages. These stages represent diverse neurobiological mechanisms that are differentially involved in the transition from recreational to compulsive drug use and from positive to negative reinforcement. The progression from recreational to compulsive substance use is associated with downregulation of the brain reward systems and upregulation of the brain stress systems. Individual differences in the neurobiological systems that underlie the processing of reward, incentive salience, habits, stress, pain, and executive function may explain (i) the vulnerability to substance-use disorder; (ii) the diversity of emotional, motivational, and cognitive profiles of individuals with substance-use disorders; and (iii) heterogeneous responses to cognitive and pharmacological treatments. Characterization of the neuropsychological mechanisms that underlie individual differences in addiction-like behaviors is the key to understanding the mechanisms of addiction and development of personalized pharmacotherapy

Analytical assessment of mine water rebound. Case study Ruhr coal basin

This study aims to assess key factors that influence mine water rebound on the example of a large amount of hard coal mines flooded or being flooded in Europe. Three German mines have been selected for a detailed study. A mathematical model based on analytical formulae of seepage theory has been employed to calculate time-dependent radial inflow to the shaft simulated as a big well in vertically heterogeneous rocks. The results of modelling showed good conformity with measurements for all studied mines. Besides, we evaluated the sensitivity of the model output to parameter variations for mine water level and initial inflow to the mine