Continuum Foreground Polarization and Na i Absorption in Type Ia SNe

We present a study of the continuum polarization over the 400-600 nm range of 19 SNe Ia obtained with FORS at the VLT. We separate them into those that show Na i D lines at the velocity of their hosts and those that do not. Continuum polarization of the sodium sample near maximum light displays a broad range of values, from extremely polarized cases like SN 2006X to almost unpolarized ones like SN 2011ae. The non-sodium sample shows, typically, smaller polarization values. The continuum polarization of the sodium sample in the 400-600 nm range is linear with wavelength and can be characterized by the mean polarization (Pmean). Its values span a wide range and show a linear correlation with color, color excess, and extinction in the visual band. Larger dispersion correlations were found with the equivalent width of the Na i D and Ca ii H and K lines, and also a noisy relation between Pmean and RV, the ratio of total to selective extinction. Redder SNe show stronger continuum polarization, with larger color excesses and extinctions. We also confirm that high continuum polarization is associated with small values of RV. The correlation between extinction and polarization - and polarization angles - suggest that the dominant fraction of dust polarization is imprinted in interstellar regions of the host galaxies. We show that Na i D lines from foreground matter in the SN host are usually associated with non-galactic ISM, challenging the typical assumptions in foreground interstellar polarization models

Tevatron Beam Halo Collimation System: Design, Operational Experience and New Methods

Collimation of proton and antiproton beams in the Tevatron collider is required to protect CDF and D0 detectors and minimize their background rates, to keep irradiation of superconducting magnets under control, to maintain long-term operational reliability, and to reduce the impact of beam-induced radiation on the environment. In this article we briefly describe the design, practical implementation and performance of the collider collimation system, methods to control transverse and longitudinal beam halo and two novel collimation techniques tested in the Tevatron.Comment: 25 p

Long-Term Efficacy and Safety of Adalimumab in Pediatric Patients with Crohn's Disease

Background: IMAgINE 1 assessed 52-week efficacy and safety of adalimumab in children with moderate to severe Crohn's disease. Long-Term efficacy and safety of adalimumab for patients who entered the IMAgINE 2 extension are reported. Methods: Patients who completed IMAgINE 1 could enroll in IMAgINE 2. Endpoints assessed from weeks 0 to 240 of IMAgINE 2 were Pediatric Crohn's Disease Activity Index remission (Pediatric Crohn's Disease Activity Index ≤ 10) and response (Pediatric Crohn's Disease Activity Index decrease ≥15 from IMAgINE 1 baseline) using observed analysis and hybrid nonresponder imputation (hNRI). For hNRI, discontinued patients were imputed as failures unless they transitioned to commercial adalimumab (with study site closure) or adult care, where last observation was carried forward. Corticosteroid-free remission in patients receiving corticosteroids at IMAgINE 1 baseline, discontinuation of immunomodulators (IMMs) in patients receiving IMMs at IMAgINE 2 baseline, and linear growth improvement were reported as observed. Adverse events were assessed for patients receiving ≥1 adalimumab dose in IMAgINE 1 and 2 through January 2015. Results: Of 100 patients enrolled in IMAgINE 2, 41% and 48% achieved remission and response (hNRI) at IMAgINE 2 week 240. Remission rates were maintained by 45% (30/67, hNRI) of patients who entered IMAgINE 2 in remission. At IMAgINE 2 week 240, 63% (12/19) of patients receiving corticosteroids at IMAgINE 1 baseline achieved corticosteroid-free remission and 30% (6/20) of patients receiving IMMs at IMAgINE 2 baseline discontinued IMMs. Adalimumab treatment led to growth velocity normalization. No new safety signals were identified. Conclusions: Efficacy and safety profiles of prolonged adalimumab treatment in children with Crohn's disease were consistent with IMAgINE 1 and adult Crohn's disease adalimumab trials

Oleic acid triggers metabolic rewiring of T cells poising them for T helper 9 differentiation

T cells are the most common immune cells in atherosclerotic plaques, and the function of T cells can be altered by fatty acids. Here, we show that pre-exposure of CD4+ T cells to oleic acid, an abundant fatty acid linked to cardiovascular events, upregulates core metabolic pathways and promotes differentiation into interleukin-9 (IL-9)-producing cells upon activation. RNA sequencing of non-activated T cells reveals that oleic acid upregulates genes encoding key enzymes responsible for cholesterol and fatty acid biosynthesis. Transcription footprint analysis links these expression changes to the differentiation toward TH9 cells, a pro-atherogenic subset. Spectral flow cytometry shows that pre-exposure to oleic acid results in a skew toward IL-9+-producing T cells upon activation. Importantly, pharmacological inhibition of either cholesterol or fatty acid biosynthesis abolishes this effect, suggesting a beneficial role for statins beyond cholesterol lowering. Taken together, oleic acid may affect inflammatory diseases like atherosclerosis by rewiring T cell metabolism.</p

Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features

Genome-wide association studies have associated thousands of genetic variants with complex traits and diseases, but pinpointing the causal variant(s) among those in tight linkage disequilibrium with each associated variant remains a major challenge. Here, we use seven experimental assays to characterize all common variants at the multiple disease-associated TNFAIP3 locus in five disease-relevant immune cell lines, based on a set of features related to regulatory potential. Trait/disease-associated variants are enriched among SNPs prioritized based on either: (1) residing within CRISPRi-sensitive regulatory regions, or (2) localizing in a chromatin accessible region while displaying allele-specific reporter activity. Of the 15 trait/disease-associated haplotypes at TNFAIP3, 9 have at least one variant meeting one or both of these criteria, 5 of which are further supported by genetic fine-mapping. Our work provides a comprehensive strategy to characterize genetic variation at important disease-associated loci, and aids in the effort to identify trait causal genetic variants

Mutation of a single residue, β-glutamate-20, alters protein–lipid interactions of light harvesting complex II

It is well established that assembly of the peripheral antenna complex, LH2, is required for proper photosynthetic membrane biogenesis in the purple bacterium Rhodobacter sphaeroides. The underlying interactions are, as yet, not understood. Here we examined the relationship between the morphology of the photosynthetic membrane and the lipid–protein interactions at the LH2–lipid interface. The non-bilayer lipid, phosphatidylethanolamine, is shown to be highly enriched in the boundary lipid phase of LH2. Sequence alignments indicate a putative lipid binding site, which includes β-glutamate-20 and the adjacent carotenoid end group. Replacement of β-glutamate-20 with alanine results in significant reduction of phosphatidylethanolamine and concomitant raise in phosphatidylcholine in the boundary lipid phase of LH2 without altering the lipid composition of the bulk phase. The morphology of the LH2 housing membrane is, however, unaffected by the amino acid replacement. In contrast, simultaneous modification of glutamate-20 and exchange of the carotenoid sphaeroidenone with neurosporene results in significant enlargement of the vesicular membrane invaginations. These findings suggest that the LH2 complex, specifically β-glutamate-20 and the carotenoids' polar head group, contribute to the shaping of the photosynthetic membrane by specific interactions with surrounding lipid molecules