Evidence of epistasis between Interleukin-1 and Selenoprotein-S with susceptibility to rheumatoid arthritis

Objective: Selenoprotein-S (SELS) is involved in the stress response within the endoplasmic reticulum (ER) and inflammation. Recently, promoter variants in the SELS gene were shown to be associated with plasma levels of interleukin (IL)6, IL1β and tumour necrosis factor (TNF). It was hypothesised that these variants could influence rheumatoid arthritis (RA) susceptibility and may interact with functional single nucleotide polymorphisms (SNPs) in the genes for IL1, IL6 and TNF. Methods: Genotyping was performed in 988 unrelated healthy controls and 965 patients with RA. Stratified analysis was used to test for interactions. Single gene effects and evidence of epistasis were investigated using the Mantel–Haenszel (M–H) test and the linkage disequilibrium (LD)-based statistic. Results: No association of SELS −105 genotype and RA susceptibility was detected. Stratification of SELS −105 genotypes by IL1 −511 genotypes showed that the disease risk (comparing AA/GA to GG at the SELS −105 locus) in individuals with the GG/AG genotype at the IL1β −511 locus was significantly lower than that in individuals having the AA genotype at the IL1β −511 locus (odds ratio (OR): 0.9 and 2.3, respectively; p = 0.004 by M–H test). Significant epistasis was also detected using the LD-based statistic (p = <0.001). No interaction was observed between SELS −105 and IL6 or TNF variants. Conclusion: Our results reveal evidence of strong epistasis in two genes in the IL1 production pathway and highlight the potential importance of gene–gene interactions in the pathogenesis of RA

Limits on mode coherence in pulsating DA white dwarfs due to a nonstatic convection zone

The standard theory of pulsations deals with the frequencies and growth rates of infinitesimal perturbations in a stellar model. Modes that are calculated to be linearly driven should increase their amplitudes exponentially with time; the fact that nearly constant amplitudes are usually observed is evidence that nonlinear mechanisms inhibit the growth of finite-amplitude pulsations. Models predict that the mass of convection zones in pulsating hydrogen-atmosphere (DAV) white dwarfs is very sensitive to temperature (i.e., M_CZ∝T_eff^-90), leading to the possibility that even low-amplitude pulsators may experience significant nonlinear effects. In particular, the outer turning point of finite-amplitude g-mode pulsations can vary with the local surface temperature, producing a reflected wave that is out of phase with what is required for a standing wave. This can lead to a lack of coherence of the mode and a reduction in its global amplitude. In this paper we show that (1) whether a mode is calculated to propagate to the base of the convection zone is an accurate predictor of its width in the Fourier spectrum, (2) the phase shifts produced by reflection from the outer turning point are large enough to produce significant damping, and (3) amplitudes and periods are predicted to increase from the blue edge to the middle of the instability strip, and subsequently decrease as the red edge is approached. This amplitude decrease is in agreement with the observational data while the period decrease has not yet been systematically studied.Published versio

Bandlimited approximations to the truncated Gaussian and applications

In this paper we extend the theory of optimal approximations of functions $f: \R \to \R$ in the $L^1(\R)$-metric by entire functions of prescribed exponential type (bandlimited functions). We solve this problem for the truncated and the odd Gaussians using explicit integral representations and fine properties of truncated theta functions obtained via the maximum principle for the heat operator. As applications, we recover most of the previously known examples in the literature and further extend the class of truncated and odd functions for which this extremal problem can be solved, by integration on the free parameter and the use of tempered distribution arguments. This is the counterpart of the work \cite{CLV}, where the case of even functions is treated.Comment: to appear in Const. Appro

pi-NN Coupling Constants from NN Elastic Data between 210 and 800 Mev

High partial waves for $pp$ and $np$ elastic scattering are examined critically from 210 to 800 MeV. Non-OPE contributions are compared with predictions from theory. There are some discrepancies, but sufficient agreement that values of the $\pi NN$ coupling constants $g_0^2$ for $\pi ^0$ exchange and $g^2_{c}$ for charged $\pi$ exchange can be derived. Results are $g^2_0 = 13.91 \pm 0.13 \pm 0.07$ and $g^2_c = 13.69 \pm 0.15 \pm 0.24$, where the first error is statistical and the second is an estimate of the likely systematic error, arising mostly from uncertainties in the normalisation of total cross sections and $d\sigma/d\Omega$.Comment: 21 pages of LaTeX, UI-NTH-940

The mental health of university students in the United Kingdom

There are increasing concerns globally about the mental health of students (Kadison,& Digeronimo, 2004). In the UK, the actual incidence of mental disturbance is unknown, although university counselling services report increased referrals (Association of University & College Counselling, 2011). This study assesses the levels of mental illness in undergraduate students to examine whether widening participation in education has resulted in increases as hypothesized by the UK Royal College of Psychiatrists (2003, 2011). Patterns of disturbance across years are compared to identify where problems arise. Students (N = 1197) completed the General Health Questionnaire-28 either on day one at university or midway through the academic year for first, second and third year students. Rates of mental illness in students equalled those of the general population but only 5.1% were currently receiving treatment. Second year students reported the most significant increases in psychiatric symptoms. Factors contributing to the problem are discussed

A white dwarf with transiting circumstellar material far outside the Roche limit

We report the discovery of a white dwarf exhibiting deep, irregularly shaped transits, indicative of circumstellar planetary debris. Using Zwicky Transient Facility DR2 photometry of ZTF J013906.17+524536.89 and follow-up observations from the Las Cumbres Observatory, we identify multiple transit events that recur every ≈107.2 days, much longer than the 4.5–4.9 hr orbital periods observed in WD 1145+017, the only other white dwarf known with transiting planetary debris. The transits vary in both depth and duration, lasting 15–25 days and reaching 20%–45% dips in flux. Optical spectra reveal strong Balmer lines, identifying the white dwarf as a DA with T_eff=10,530 ± 140K and log(g) =7.86 ± 0.06. A Ca ii K absorption feature is present in all spectra both in and out of transit. Spectra obtained during one night at roughly 15% transit depth show increased Ca ii K absorption with a model atmospheric fit suggesting [Ca/H] = −4.6 ± 0.3, whereas spectra taken on three nights out of transit have [Ca/H] of −5.5, −5.3, and −4.9 with similar uncertainties. While the Ca ii K line strength varies by only 2σ, we consider a predominantly interstellar origin for Ca absorption unlikely. We suggest a larger column density of circumstellar metallic gas along the line of site or increased accretion of material onto the white dwarf's surface are responsible for the Ca absorption, but further spectroscopic studies are required. In addition, high-speed time series photometry out of transit reveals variability with periods of 900 and 1030 s, consistent with ZZ Ceti pulsations.Published versio

Demonstration of a novel technique to measure two-photon exchange effects in elastic e±pe^\pm p scattering

The discrepancy between proton electromagnetic form factors extracted using unpolarized and polarized scattering data is believed to be a consequence of two-photon exchange (TPE) effects. However, the calculations of TPE corrections have significant model dependence, and there is limited direct experimental evidence for such corrections. We present the results of a new experimental technique for making direct $e^\pm p$ comparisons, which has the potential to make precise measurements over a broad range in $Q^2$ and scattering angles. We use the Jefferson Lab electron beam and the Hall B photon tagger to generate a clean but untagged photon beam. The photon beam impinges on a converter foil to generate a mixed beam of electrons, positrons, and photons. A chicane is used to separate and recombine the electron and positron beams while the photon beam is stopped by a photon blocker. This provides a combined electron and positron beam, with energies from 0.5 to 3.2 GeV, which impinges on a liquid hydrogen target. The large acceptance CLAS detector is used to identify and reconstruct elastic scattering events, determining both the initial lepton energy and the sign of the scattered lepton. The data were collected in two days with a primary electron beam energy of only 3.3 GeV, limiting the data from this run to smaller values of $Q^2$ and scattering angle. Nonetheless, this measurement yields a data sample for $e^\pm p$ with statistics comparable to those of the best previous measurements. We have shown that we can cleanly identify elastic scattering events and correct for the difference in acceptance for electron and positron scattering. The final ratio of positron to electron scattering: $R=1.027\pm0.005\pm0.05$ for $=0.206$ GeV$^2$ and $0.830\leq \epsilon\leq 0.943$

Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up

In the International Visible Trait Genetics (VisiGen) Consortium, we investigated the genetics of human skin color by combining a series of genome-wide association studies (GWAS) in a total of 17,262 Europeans with functional follow-up of discovered loci. Our GWAS provide the first genome-wide significant evidence for chromosome 20q11.22 harboring the ASIP gene being explicitly associated with skin color in Europeans. In addition, genomic loci at 5p13.2 (SLC45A2), 6p25.3 (IRF4), 15q13.1 (HERC2/OCA2), and 16q24.3 (MC1R) were confirmed to be involved in skin coloration in Europeans. In follow-up gene expression and regulation studies of 22 genes in 20q11.22, we highlighted two novel genes EIF2S2 and GSS, serving as competing functional candidates in this region and providing future research lines. A genetically inferred skin color score obtained from the 9 top-associated SNPs from 9 genes in 940 worldwide samples (HGDP-CEPH) showed a clear gradual pattern in Western Eurasians similar to the distribution of physical skin color, suggesting the used 9 SNPs as suitable markers for DNA prediction of skin color in Europeans and neighboring populations, relevant in future forensic and anthropological investigations

Eigenmodes and growth rates of relativistic current filamentation instability in a collisional plasma

I theoretically found eigenmodes and growth rates of relativistic current filamentation instability in collisional regimes, deriving a generalized dispersion relation from self-consistent beam-Maxwell equations. For symmetrically counterstreaming, fully relativistic electron currents, the collisional coupling between electrons and ions creates the unstable modes of growing oscillation and wave, which stand out for long-wavelength perturbations. In the stronger collisional regime, the growing oscillatory mode tends to be dominant for all wavelengths. In the collisionless limit, those modes vanish, while maintaining another purely growing mode that exactly coincides with a standard relativistic Weibel mode. It is also shown that the effects of electron-electron collisions and thermal spread lower the growth rate of the relativistic Weibel instability. The present mechanisms of filamentation dynamics are essential for transport of homogeneous electron beam produced by the interaction of high power laser pulses with plasma.Comment: 44 pages, 12 figures. Accepted for publication in Phys. Rev.