Submillimeter wavelength survey of the galactic plane from l = -5 deg to l = +62 deg: Structure and energetics of the inner disk

Results from a large scale survey of the first quadrant of the Milky Way galactic plane at wavelengths of 150, 250, and 300 microns with a 10x10 arcmin beam are presented. The emission detected in the survey arises from compact sources, most of which are identified with known peaks of 5 GHz and/or CO emission, and from an underlying diffuse background with a typical angular width of approximately 0.9 deg (FWHM) which accounts for most of the emission. A total of 80 prominent discrete sources were identified and characterized, of which about half were not previously reported at far infrared wavelengths. The total infrared luminosity within the solar circle is approximately 1 to 2x10 to the 10th power L sub 0, and is probably emitted by dust that resides in molecular clouds

A characteristic lengthscale causes anomalous size effects and boundary programmability in mechanical metamaterials

The architecture of mechanical metamaterialsis designed to harness geometry, non-linearity and topology to obtain advanced functionalities such as shape morphing, programmability and one-way propagation. While a purely geometric framework successfully captures the physics of small systems under idealized conditions, large systems or heterogeneous driving conditions remain essentially unexplored. Here we uncover strong anomalies in the mechanics of a broad class of metamaterials, such as auxetics, shape-changers or topological insulators: a non-monotonic variation of their stiffness with system size, and the ability of textured boundaries to completely alter their properties. These striking features stem from the competition between rotation-based deformations---relevant for small systems---and ordinary elasticity, and are controlled by a characteristic length scale which is entirely tunable by the architectural details. Our study provides new vistas for designing, controlling and programming the mechanics of metamaterials in the thermodynamic limit.Comment: Main text has 4 pages, 4 figures + Methods and Supplementary Informatio

The COBE Diffuse Infrared Background Experiment Search for the Cosmic Infrared Background: IV. Cosmological Implications

In this paper we examine the cosmological constraints of the recent DIRBE and FIRAS detection of the extragalactic background light between 125-5000 microns on the metal and star formation histories of the universe.Comment: 38 pages and 9 figures. Accepted for publications in The Astrophysical Journa

Dupilumab provides rapid and sustained improvement in SCORAD outcomes in adults with moderate-to-severe atopic dermatitis: combined results of four randomized phase 3 trials

Background:Dupilumab, a first-in-class therapy targeting the two key cytokines involved in the persistent underlying inflammatory pathway in atopic dermatitis (AD), is approved for treatment of moderate-to-severe AD in Europe, USA, Japan and several other countries. Objective:To assess dupilumab effects on SCORing Atopic Dermatitis (SCORAD) and component scores (objective and subjective SCORAD) over time in adults with moderate-to-severe AD. Methods:Thispost hocanalysis included 2,444 patients in four placebo-controlled, double-blind, randomized, phase 3 trials. SOLO 1 and 2 (NCT02277743; NCT02277769) evaluated 16 weeks of dupilumab monotherapy against placebo. CAFe (NCT02755649) and CHRONOS (NCT02260986) evaluated dupilumab with concomitant topical corticosteroids (TCS) against TCS alone for 16 and 52 weeks, respectively. Results:2,444 patients randomized to treatment in SOLO 1 and 2 (N = 1,379), CAFe (N = 325) and CHRONOS (N = 740) were analyzed. Dupilumab treatment significantly improved overall SCORAD and individual components as early as Week 1 or 2, with significant and clinically meaningful differences vs. control through end of treatment (p < .0001). These results occurred irrespective of dupilumab regimen, 300 mg subcutaneously weekly or every 2 weeks. Conclusions:In four large phase 3 trials in adults with moderate-to-severe AD, dupilumab treatment with or without concomitant TCS resulted in rapid and sustained improvements in all SCORAD outcomes vs. placebo or TCS alone

Two Phase 3 Trials of Dupilumab versus Placebo in Atopic Dermatitis.

BACKGROUND Dupilumab, a human monoclonal antibody against interleukin-4 receptor alpha, inhibits signaling of interleukin-4 and interleukin-13, type 2 cytokines that may be important drivers of atopic or allergic diseases such as atopic dermatitis. METHODS In two randomized, placebo-controlled, phase 3 trials of identical design (SOLO 1 and SOLO 2), we enrolled adults with moderate-to-severe atopic dermatitis whose disease was inadequately controlled by topical treatment. Patients were randomly assigned in a 1:1:1 ratio to receive, for 16 weeks, subcutaneous dupilumab (300 mg) or placebo weekly or the same dose of dupilumab every other week alternating with placebo. The primary outcome was the proportion of patients who had both a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline at week 16. RESULTS We enrolled 671 patients in SOLO 1 and 708 in SOLO 2. In SOLO 1, the primary outcome occurred in 85 patients (38%) who received dupilumab every other week and in 83 (37%) who received dupilumab weekly, as compared with 23 (10%) who received placebo (P<0.001 for both comparisons with placebo). The results were similar in SOLO 2, with the primary outcome occurring in 84 patients (36%) who received dupilumab every other week and in 87 (36%) who received dupilumab weekly, as compared with 20 (8%) who received placebo (P<0.001 for both comparisons). In addition, in the two trials, an improvement from baseline to week 16 of at least 75% on the Eczema Area and Severity Index was reported in significantly more patients who received each regimen of dupilumab than in patients who received placebo (P<0.001 for all comparisons). Dupilumab was also associated with improvement in other clinical end points, including reduction in pruritus and symptoms of anxiety or depression and improvement in quality of life. Injection-site reactions and conjunctivitis were more frequent in the dupilumab groups than in the placebo groups. CONCLUSIONS In two phase 3 trials of identical design involving patients with atopic dermatitis, dupilumab improved the signs and symptoms of atopic dermatitis, including pruritus, symptoms of anxiety and depression, and quality of life, as compared with placebo. Trials of longer duration are needed to assess the long-term effectiveness and safety of dupilumab. (Funded by Sanofi and Regeneron Pharmaceuticals; SOLO 1 ClinicalTrials.gov number, NCT02277743; SOLO 2 ClinicalTrials .gov number, NCT02277769.

Single Nucleotide Polymorphisms That Increase Expression of the Guanosine Triphosphatase RAC1 Are Associated With Ulcerative Colitis

BACKGROUND & AIMS: RAC1 is a GTPase that has an evolutionarily conserved role in coordinating immune defenses, from plants to mammals. Chronic inflammatory bowel diseases (IBD) are associated with dysregulation of immune defenses. We studied the role of RAC1 in IBD using human genetic and functional studies and animal models of colitis. METHODS: We used a candidate gene approach to HapMap-Tag single nucleotide polymorphisms (SNPs) in a discovery cohort; findings were confirmed in 2 additional cohorts. RAC1 mRNA expression was examined from peripheral blood cells of patients. Colitis was induced in mice with conditional disruption of Rac1 in phagocytes by administration of dextran sulphate sodium (DSS). RESULTS: We observed a genetic association between RAC1 with ulcerative colitis (UC) in a discovery cohort, 2 independent replication cohorts, and in combined analysis for the SNPs rs10951982 (Pcombined UC = 3.3 × 10–8, odds ratio [OR]=1.43 [1.26–1.63]) and rs4720672 (Pcombined UC=4.7 × 10–6, OR=1.36 [1.19–1.58]). Patients with IBD who had the rs10951982 risk allele had increased expression of RAC1, compared to those without this allele. Conditional disruption of Rac1 in macrophage and neutrophils of mice protected them against DSS-induced colitis. CONCLUSION: Studies of human tissue samples and knockout mice demonstrated a role for the GTPase RAC1 in the development of UC; increased expression of RAC1 was associated with susceptibility to colitis