Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

Assessment of animal hosts of pathogenic Leptospira in northern Tanzania

Funding: This work was supported by the Wellcome Trust (grant number 096400/Z/11/Z; https://wellcome.ac.uk/). JEBH, VPM, JAC, and SC received support from the Research Councils UK, UK Department for International Development, and UK Biotechnology and Biological Sciences Research Council (BBSRC) (grant numbers BB/J010367/1, BB/L018926, BB/L017679, BB/L018845; http://www.bbsrc.ac.uk/). JAC and VPM also received support from the US National Institutes of Health (NIH)-National Science Foundation (NSF) Ecology and Evolution of Infectious Disease program (R01TW009237; https://www.fic.nih.gov/programs/pages/ecology-infectious-diseases.aspx). MM received support from the BBSRC East of Scotland Bioscience Doctoral Training Partnership (http://www.eastscotbiodtp.ac.uk/). MJM received support from a University of Otago Frances G. Cotter Scholarship and a University of Otago MacGibbon PhD Travel Fellowship (http://www.otago.ac.nz/). VPM and JAC received support from the US National Institutes of Health National Institute for Allergy and Infectious (grant number R01 AI121378; https://www.niaid.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: Datasets supporting this manuscript are available through: http://dx.doi.org/10.5525/gla.researchdata.582. Unique sequences generated through this study are available through GenBank (accession numbers MF955862 to MF955882).Peer reviewedPublisher PD

Unbounded violation of tripartite Bell inequalities

We prove that there are tripartite quantum states (constructed from random unitaries) that can lead to arbitrarily large violations of Bell inequalities for dichotomic observables. As a consequence these states can withstand an arbitrary amount of white noise before they admit a description within a local hidden variable model. This is in sharp contrast with the bipartite case, where all violations are bounded by Grothendieck's constant. We will discuss the possibility of determining the Hilbert space dimension from the obtained violation and comment on implications for communication complexity theory. Moreover, we show that the violation obtained from generalized GHZ states is always bounded so that, in contrast to many other contexts, GHZ states do in this case not lead to extremal quantum correlations. The results are based on tools from the theories of operator spaces and tensor norms which we exploit to prove the existence of bounded but not completely bounded trilinear forms from commutative C*-algebras.Comment: Substantial changes in the presentation to make the paper more accessible for a non-specialized reade

Precision Measurement of the Proton and Deuteron Spin Structure Functions g2 and Asymmetries A2

We have measured the spin structure functions g2p and g2d and the virtual photon asymmetries A2p and A2d over the kinematic range 0.02 < x < 0.8 and 0.7 < Q^2 < 20 GeV^2 by scattering 29.1 and 32.3 GeV longitudinally polarized electrons from transversely polarized NH3 and 6LiD targets. Our measured g2 approximately follows the twist-2 Wandzura-Wilczek calculation. The twist-3 reduced matrix elements d2p and d2n are less than two standard deviations from zero. The data are inconsistent with the Burkhardt-Cottingham sum rule if there is no pathological behavior as x->0. The Efremov-Leader-Teryaev integral is consistent with zero within our measured kinematic range. The absolute value of A2 is significantly smaller than the sqrt[R(1+A1)/2] limit.Comment: 12 pages, 4 figures, 2 table

Launch of the Space experiment PAMELA

PAMELA is a satellite borne experiment designed to study with great accuracy cosmic rays of galactic, solar, and trapped nature in a wide energy range protons: 80 MeV-700 GeV, electrons 50 MeV-400 GeV). Main objective is the study of the antimatter component: antiprotons (80 MeV-190 GeV), positrons (50 MeV-270 GeV) and search for antimatter with a precision of the order of 10^-8). The experiment, housed on board the Russian Resurs-DK1 satellite, was launched on June, 15, 2006 in a 350*600 km orbit with an inclination of 70 degrees. The detector is composed of a series of scintillator counters arranged at the extremities of a permanent magnet spectrometer to provide charge, Time-of-Flight and rigidity information. Lepton/hadron identification is performed by a Silicon-Tungsten calorimeter and a Neutron detector placed at the bottom of the device. An Anticounter system is used offline to reject false triggers coming from the satellite. In self-trigger mode the Calorimeter, the neutron detector and a shower tail catcher are capable of an independent measure of the lepton component up to 2 TeV. In this work we describe the experiment, its scientific objectives and the performance in the first months after launch.Comment: Accepted for publication on Advances in Space Researc

Dust Devil Tracks

Dust devils that leave dark- or light-toned tracks are common on Mars and they can also be found on the Earth’s surface. Dust devil tracks (hereinafter DDTs) are ephemeral surface features with mostly sub-annual lifetimes. Regarding their size, DDT widths can range between ∼1 m and ∼1 km, depending on the diameter of dust devil that created the track, and DDT lengths range from a few tens of meters to several kilometers, limited by the duration and horizontal ground speed of dust devils. DDTs can be classified into three main types based on their morphology and albedo in contrast to their surroundings; all are found on both planets: (a) dark continuous DDTs, (b) dark cycloidal DDTs, and (c) bright DDTs. Dark continuous DDTs are the most common type on Mars. They are characterized by their relatively homogenous and continuous low albedo surface tracks. Based on terrestrial and martian in situ studies, these DDTs most likely form when surficial dust layers are removed to expose larger-grained substrate material (coarse sands of ≥500 μm in diameter). The exposure of larger-grained materials changes the photometric properties of the surface; hence leading to lower albedo tracks because grain size is photometrically inversely proportional to the surface reflectance. However, although not observed so far, compositional differences (i.e., color differences) might also lead to albedo contrasts when dust is removed to expose substrate materials with mineralogical differences. For dark continuous DDTs, albedo drop measurements are around 2.5 % in the wavelength range of 550–850 nm on Mars and around 0.5 % in the wavelength range from 300–1100 nm on Earth. The removal of an equivalent layer thickness around 1 μm is sufficient for the formation of visible dark continuous DDTs on Mars and Earth. The next type of DDTs, dark cycloidal DDTs, are characterized by their low albedo pattern of overlapping scallops. Terrestrial in situ studies imply that they are formed when sand-sized material that is eroded from the outer vortex area of a dust devil is redeposited in annular patterns in the central vortex region. This type of DDT can also be found in on Mars in orbital image data, and although in situ studies are lacking, terrestrial analog studies, laboratory work, and numerical modeling suggest they have the same formation mechanism as those on Earth. Finally, bright DDTs are characterized by their continuous track pattern and high albedo compared to their undisturbed surroundings. They are found on both planets, but to date they have only been analyzed in situ on Earth. Here, the destruction of aggregates of dust, silt and sand by dust devils leads to smooth surfaces in contrast to the undisturbed rough surfaces surrounding the track. The resulting change in photometric properties occurs because the smoother surfaces have a higher reflectance compared to the surrounding rough surface, leading to bright DDTs. On Mars, the destruction of surficial dust-aggregates may also lead to bright DDTs. However, higher reflective surfaces may be produced by other formation mechanisms, such as dust compaction by passing dust devils, as this may also cause changes in photometric properties. On Mars, DDTs in general are found at all elevations and on a global scale, except on the permanent polar caps. DDT maximum areal densities occur during spring and summer in both hemispheres produced by an increase in dust devil activity caused by maximum insolation. Regionally, dust devil densities vary spatially likely controlled by changes in dust cover thicknesses and substrate materials. This variability makes it difficult to infer dust devil activity from DDT frequencies. Furthermore, only a fraction of dust devils leave tracks. However, DDTs can be used as proxies for dust devil lifetimes and wind directions and speeds, and they can also be used to predict lander or rover solar panel clearing events. Overall, the high DDT frequency in many areas on Mars leads to drastic albedo changes that affect large-scale weather patterns

An Extreme Solar Event of 20 January 2005: Properties of the Flare and the Origin of Energetic Particles

The extreme solar and SEP event of 20 January 2005 is analyzed from two perspectives. Firstly, we study features of the main phase of the flare, when the strongest emissions from microwaves up to 200 MeV gamma-rays were observed. Secondly, we relate our results to a long-standing controversy on the origin of SEPs arriving at Earth, i.e., acceleration in flares, or shocks ahead of CMEs. All emissions from microwaves up to 2.22 MeV line gamma-rays during the main flare phase originated within a compact structure located just above sunspot umbrae. A huge radio burst with a frequency maximum at 30 GHz was observed, indicating the presence of a large number of energetic electrons in strong magnetic fields. Thus, protons and electrons responsible for flare emissions during its main phase were accelerated within the magnetic field of the active region. The leading, impulsive parts of the GLE, and highest-energy gamma-rays identified with pi^0-decay emission, are similar and correspond in time. The origin of the pi^0-decay gamma-rays is argued to be the same as that of lower energy emissions. We estimate the sky-plane speed of the CME to be 2000-2600 km/s, i.e., high, but of the same order as preceding non-GLE-related CMEs from the same active region. Hence, the flare itself rather than the CME appears to determine the extreme nature of this event. We conclude that the acceleration, at least, to sub-relativistic energies, of electrons and protons, responsible for both the flare emissions and the leading spike of SEP/GLE by 07 UT, are likely to have occurred simultaneously within the flare region. We do not rule out a probable contribution from particles accelerated in the CME-driven shock for the leading GLE spike, which seemed to dominate later on.Comment: 34 pages, 14 Postscript figures. Solar Physics, accepted. A typo corrected. The original publication is available at http://www.springerlink.co

Field Measurements of Terrestrial and Martian Dust Devils

Surface-based measurements of terrestrial and martian dust devils/convective vortices provided from mobile and stationary platforms are discussed. Imaging of terrestrial dust devils has quantified their rotational and vertical wind speeds, translation speeds, dimensions, dust load, and frequency of occurrence. Imaging of martian dust devils has provided translation speeds and constraints on dimensions, but only limited constraints on vertical motion within a vortex. The longer mission durations on Mars afforded by long operating robotic landers and rovers have provided statistical quantification of vortex occurrence (time-of-sol, and recently seasonal) that has until recently not been a primary outcome of more temporally limited terrestrial dust devil measurement campaigns. Terrestrial measurement campaigns have included a more extensive range of measured vortex parameters (pressure, wind, morphology, etc.) than have martian opportunities, with electric field and direct measure of dust abundance not yet obtained on Mars. No martian robotic mission has yet provided contemporaneous high frequency wind and pressure measurements. Comparison of measured terrestrial and martian dust devil characteristics suggests that martian dust devils are larger and possess faster maximum rotational wind speeds, that the absolute magnitude of the pressure deficit within a terrestrial dust devil is an order of magnitude greater than a martian dust devil, and that the time-of-day variation in vortex frequency is similar. Recent terrestrial investigations have demonstrated the presence of diagnostic dust devil signals within seismic and infrasound measurements; an upcoming Mars robotic mission will obtain similar measurement types

Dust Devil Populations and Statistics

The highly-skewed diameter and pressure drop distributions of dust devils on Earth and Mars are noted, and challenges of presenting and comparing different types of observations are discussed. The widely- held view that Martian dust devils are larger than Earth\u27s is critically-assessed: the question is confounded somewhat by different observation techniques, but some indication of a ~3x larger population on Mars is determined. The largest and most intense (in a relative pressure sense) devils recorded are on Mars, although the largest reported number density is on Earth. The difficulties of concepts used in the literature of \u27average\u27 diameter, pressure cross section, and area fraction are noted in the context of estimating population-integral effects such as dust lifting

Introducing an adolescent cognitive maturity index

Children show substantial variation in the rate of physical, cognitive, and social maturation as they traverse adolescence and enter adulthood. Differences in developmental paths are thought to underlie individual differences in later life outcomes, however, there remains a lack of consensus on the normative trajectory of cognitive maturation in adolescence. To address this problem, we derive a Cognitive Maturity Index (CMI), to estimate the difference between chronological and cognitive age predicted with latent factor estimates of inhibitory control, risky decision-making and emotional processing measured with standard neuropsychological instruments. One hundred and forty-one children from the Adolescent Development Study (ADS) were followed longitudinally across three time points from ages 11–14, 13–16, and 14–18. Age prediction with latent factor estimates of cognitive skills approximated age within ±10 months (r = 0.71). Males in advanced puberty displayed lower cognitive maturity relative to peers of the same age; manifesting as weaker inhibitory control, greater risk-taking, desensitization to negative affect, and poor recognition of positive affect