Can AMS-02 discriminate the origin of an anti-proton signal?

Indirect searches can be used to test dark matter models against expected signals in various channels, in particular antiprotons. With antiproton data available soon at higher and higher energies, it is important to test the dark matter hypothesis against alternative astrophysical sources, e.g. econdaries accelerated in supernova remnants. We investigate the two signals from different dark matter models and different supernova remnant parameters, as forecasted for the AMS-02, and show that they present a significant degeneracy

Reviving calm technology in the e-tourism context

Tourism industry practitioners should understand the controversial nature of the information and communication technology (ICT) proliferation to ensure the ICT solutions do not consume too much of their attention, thus jeopardizing consumer enjoyment of tourism services. The concept of calm technology or calm design serves this purpose. Calm design suggests that technology should quietly recede in the background and come into play with users when and if required, thus delivering and/or enhancing a desired experience. Although this concept is of relevance to e-tourism, until recently, it has never been considered within. This is where this paper contributes to knowledge as, for the first time, it introduces calm design into the e-tourism context and critically evaluates the determinants of its broader adoption within the tourism industry. It positions calm design within the e-tourism realm, discusses its implications for customer service management, supply chain management and destination management, and discloses opportunities for future research

Evidence for dark matter in the inner Milky Way

The ubiquitous presence of dark matter in the universe is today a central tenet in modern cosmology and astrophysics. Ranging from the smallest galaxies to the observable universe, the evidence for dark matter is compelling in dwarfs, spiral galaxies, galaxy clusters as well as at cosmological scales. However, it has been historically difficult to pin down the dark matter contribution to the total mass density in the Milky Way, particularly in the innermost regions of the Galaxy and in the solar neighbourhood. Here we present an up-to-date compilation of Milky Way rotation curve measurements, and compare it with state-of-the-art baryonic mass distribution models. We show that current data strongly disfavour baryons as the sole contribution to the galactic mass budget, even inside the solar circle. Our findings demonstrate the existence of dark matter in the inner Galaxy while making no assumptions on its distribution. We anticipate that this result will compel new model-independent constraints on the dark matter local density and profile, thus reducing uncertainties on direct and indirect dark matter searches, and will shed new light on the structure and evolution of the Galaxy.Comment: First submitted version of letter published in Nature Physics on Febuary 9, 2015: http://www.nature.com/nphys/journal/vaop/ncurrent/full/nphys3237.htm

Rare Copy Number Variants in \u3cem\u3eNRXN1\u3c/em\u3e and \u3cem\u3eCNTN6\u3c/em\u3e Increase Risk for Tourette Syndrome

Tourette syndrome (TS) is a model neuropsychiatric disorder thought to arise from abnormal development and/or maintenance of cortico-striato-thalamo-cortical circuits. TS is highly heritable, but its underlying genetic causes are still elusive, and no genome-wide significant loci have been discovered to date. We analyzed a European ancestry sample of 2,434 TS cases and 4,093 ancestry-matched controls for rare (\u3c 1% frequency) copy-number variants (CNVs) using SNP microarray data. We observed an enrichment of global CNV burden that was prominent for large (\u3e 1 Mb), singleton events (OR = 2.28, 95% CI [1.39–3.79], p = 1.2 × 10−3) and known, pathogenic CNVs (OR = 3.03 [1.85–5.07], p = 1.5 × 10−5). We also identified two individual, genome-wide significant loci, each conferring a substantial increase in TS risk (NRXN1 deletions, OR = 20.3, 95% CI [2.6–156.2]; CNTN6 duplications, OR = 10.1, 95% CI [2.3–45.4]). Approximately 1% of TS cases carry one of these CNVs, indicating that rare structural variation contributes significantly to the genetic architecture of TS

Evidence that duplications of 22q11.2 protect against schizophrenia.

A number of large, rare copy number variants (CNVs) are deleterious for neurodevelopmental disorders, but large, rare, protective CNVs have not been reported for such phenotypes. Here we show in a CNV analysis of 47 005 individuals, the largest CNV analysis of schizophrenia to date, that large duplications (1.5-3.0 Mb) at 22q11.2--the reciprocal of the well-known, risk-inducing deletion of this locus--are substantially less common in schizophrenia cases than in the general population (0.014% vs 0.085%, OR=0.17, P=0.00086). 22q11.2 duplications represent the first putative protective mutation for schizophrenia

A Rare Functional Noncoding Variant at the GWAS-Implicated MIR137/MIR2682 Locus Might Confer Risk to Schizophrenia and Bipolar Disorder

Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and MIR2682 (miR2682), two microRNA genes important for neuronal function. We sequenced ∼6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 × 10−4). We further identified its risk allele T in 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression

Investigating rare pathogenic/likely pathogenic exonic variation in bipolar disorder

Bipolar disorder (BD) is a serious mental illness with substantial common variant heritability. However, the role of rare coding variation in BD is not well established. We examined the protein-coding (exonic) sequences of 3,987 unrelated individuals with BD and 5,322 controls of predominantly European ancestry across four cohorts from the Bipolar Sequencing Consortium (BSC). We assessed the burden of rare, protein-altering, single nucleotide variants classified as pathogenic or likely pathogenic (P-LP) both exome-wide and within several groups of genes with phenotypic or biologic plausibility in BD. While we observed an increased burden of rare coding P-LP variants within 165 genes identified as BD GWAS regions in 3,987 BD cases (meta-analysis OR = 1.9, 95% CI = 1.3-2.8, one-sided p = 6.0 × 10-4), this enrichment did not replicate in an additional 9,929 BD cases and 14,018 controls (OR = 0.9, one-side p = 0.70). Although BD shares common variant heritability with schizophrenia, in the BSC sample we did not observe a significant enrichment of P-LP variants in SCZ GWAS genes, in two classes of neuronal synaptic genes (RBFOX2 and FMRP) associated with SCZ or in loss-of-function intolerant genes. In this study, the largest analysis of exonic variation in BD, individuals with BD do not carry a replicable enrichment of rare P-LP variants across the exome or in any of several groups of genes with biologic plausibility. Moreover, despite a strong shared susceptibility between BD and SCZ through common genetic variation, we do not observe an association between BD risk and rare P-LP coding variants in genes known to modulate risk for SCZ

Simulated Milky Way analogues: implications for dark matter direct searches

We study the implications of galaxy formation on dark matter direct detection using high resolution hydrodynamic simulations of Milky Way-like galaxies simulated within the eagle and apostle projects. We identify MilkyWay analogues that satisfy observational constraints on the Milky Way rotation curve and total stellar mass. We then extract the dark matter density and velocity distribution in the Solar neighbourhood for this set of Milky Way analogues, and use them to analyse the results of current direct detection experiments. For most Milky Way analogues, the event rates in direct detection experiments obtained from the best _t Maxwellian distribution (with peak speed of 223 { 289 km=s) are similar to those obtained directly from the simulations. As a consequence, the allowed regions and exclusion limits set by direct detection experiments in the dark matter mass and spin-independent cross section plane shift by a few GeV compared to the Standard Halo Model, at low dark matter masses. For each dark matter mass, the halo-to-halo variation of the local dark matter density results in an overall shift of the allowed regions and exclusion limits for the cross section. However, the compatibility of the possible hints for a dark matter signal from DAMA and CDMS-Si and null results from LUX and SuperCDMS is not improved

Genome-wide haplotype-based association analysis of major depressive disorder in Generation Scotland and UK Biobank

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8)Peer reviewedPublisher PD

A reference panel of 64,976 haplotypes for genotype imputation.

We describe a reference panel of 64,976 human haplotypes at 39,235,157 SNPs constructed using whole-genome sequence data from 20 studies of predominantly European ancestry. Using this resource leads to accurate genotype imputation at minor allele frequencies as low as 0.1% and a large increase in the number of SNPs tested in association studies, and it can help to discover and refine causal loci. We describe remote server resources that allow researchers to carry out imputation and phasing consistently and efficiently