Isaiah's Prophecy concerning the Shoot of Jesse and His Kingdom: Isaiah XI

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The International Critical Commentary. Chronicles

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NIR Spectroscopy of Star-Forming Galaxies at z~1.4 with Subaru/FMOS: The Mass-Metallicity Relation

We present near-infrared spectroscopic observations of star-forming galaxies at z~1.4 with FMOS on the Subaru Telescope. We observed K-band selected galaxies in the SXDS/UDS fields with K10^{9.5} Msun, and expected F(Halpha)>10^{-16} erg s^{-1} cm^{-2}. 71 objects in the sample have significant detections of Halpha. For these objects, excluding possible AGNs identified from the BPT diagram, gas-phase metallicities are obtained from [NII]/Halpha line ratio. The sample is split into three stellar mass bins, and the spectra are stacked in each stellar mass bin. The mass-metallicity relation obtained at z~1.4 is located between those at z~0.8 and z~2.2. We constrain an intrinsic scatter to be ~0.1 dex or larger in the mass-metallicity relation at z~1.4; the scatter may be larger at higher redshifts. We found trends that the deviation from the mass-metallicity relation depends on the SFR and the half light radius: Galaxies with higher SFR and larger half light radii show lower metallicities at a given stellar mass. One possible scenario for the trends is the infall of pristine gas accreted from IGM or through merger events. Our data points show larger scatter than the fundamental metallicity relation (FMR) at z~0.1 and the average metallicities slightly deviate from the FMR. The compilation of the mass-metallicity relations at z~3 to z~0.1 shows that they evolve smoothly from z~3 to z~0 without changing the shape so much except for the massive part at z~0.Comment: 20 pages, 18 figures, accepted for publication in PAS

The Subaru-XMM-Newton Deep Survey (SXDS) VIII.: Multi-wavelength Identification, Optical/NIR Spectroscopic Properties, and Photometric Redshifts of X-ray Sources

We report the multi-wavelength identification of the X-ray sources found in the Subaru-XMM-Newton Deep Survey (SXDS) using deep imaging data covering the wavelength range between the far-UV to the mid-IR. We select a primary counterpart of each X-ray source by applying the likelihood ratio method to R-band, 3.6micron, near-UV, and 24micron source catalogs as well as matching catalogs of AGN candidates selected in 1.4GHz radio and i'-band variability surveys. Once candidates of Galactic stars, ultra-luminous X-ray sources in a nearby galaxy, and clusters of galaxies are removed there are 896 AGN candidates in the sample. We conduct spectroscopic observations of the primary counterparts with multi-object spectrographs in the optical and NIR; 65\% of the X-ray AGN candidates are spectroscopically-identified. For the remaining X-ray AGN candidates, we evaluate their photometric redshift with photometric data in 15 bands. Utilising the multi-wavelength photometric data of the large sample of X-ray selected AGNs, we evaluate the stellar masses, M*, of the host galaxies of the narrow-line AGNs. The distribution of the stellar mass is remarkably constant from z=0.1 to 4.0. The relation between M* and 2--10 keV luminosity can be explained with strong cosmological evolution of the relationship between the black hole mass and M*. We also evaluate the scatter of the UV-MIR spectral energy distribution (SED) of the X-ray AGNs as a function of X-ray luminosity and absorption to the nucleus. The scatter is compared with galaxies which have redshift and stellar mass distribution matched with the X-ray AGN. The UV-NIR SEDs of obscured X-ray AGNs are similar to those of the galaxies in the matched sample. In the NIR-MIR range, the median SEDs of X-ray AGNs are redder, but the scatter of the SEDs of the X-ray AGN broadly overlaps that of the galaxies in the matched sample.Comment: Accepted for publication in PASJ Subaru special issue. 42 pages, 22 figures. Entire contents of Tables 3, 8, 9, 10, and 11, and ASCII format tables are available from http://www.astr.tohoku.ac.jp/~akiyama/SXDS/index.htm

Operational aspects of an externally driven neutron multiplier assembly concept using a Z-pinch 14-MeV Neutron Source (ZEDNA).

This report documents the key safety and operational aspects of a Z-pinch Externally Driven Nuclear Assembly (ZEDNA) reactor concept which is envisioned to be built and operated at the Z-machine facility in Technical Area IV. Operating parameters and reactor neutronic conditions are established that would meet the design requirements of the system. Accident and off-normal conditions are analyzed using a point-kinetics, one-dimensional thermo-mechanical code developed specifically for ZEDNA applications. Downwind dose calculations are presented to determine the potential dose to the collocated worker and public in the event of a hypothetical catastrophic accident. Current and magnetic impulse modeling and the debris shield design are examined for the interface between the Z machine and the ZEDNA. This work was performed as part of the Advanced Fusion Grand Challenge Laboratory Directed Research and Development Program. The conclusion of this work is that the ZEDNA concept is feasible and could be operated at the Z-machine facility without undue risk to collocated workers and the public

Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction1. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity1,2. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments

Genome-Wide Association of Body Fat Distribution in African Ancestry Populations Suggests New Loci

Central obesity, measured by waist circumference (WC) or waist-hip ratio (WHR), is a marker of body fat distribution. Although obesity disproportionately affects minority populations, few studies have conducted genome-wide association study (GWAS) of fat distribution among those of predominantly African ancestry (AA). We performed GWAS of WC and WHR, adjusted and unadjusted for BMI, in up to 33,591 and 27,350 AA individuals, respectively. We identified loci associated with fat distribution in AA individuals using meta-analyses of GWA results for WC and WHR (stage 1). Overall, 25 SNPs with single genomic control (GC)-corrected p-values<5.0×10−6 were followed-up (stage 2) in AA with WC and with WHR. Additionally, we interrogated genomic regions of previously identified European ancestry (EA) WHR loci among AA. In joint analysis of association results including both Stage 1 and 2 cohorts, 2 SNPs demonstrated association, rs2075064 at LHX2, p = 2.24×10−8 for WC-adjusted-for-BMI, and rs6931262 at RREB1, p = 2.48×10−8 for WHR-adjusted-for-BMI. However, neither signal was genome-wide significant after double GC-correction (LHX2: p = 6.5×10−8; RREB1: p = 5.7×10−8). Six of fourteen previously reported loci for waist in EA populations were significant (p<0.05 divided by the number of independent SNPs within the region) in AA studied here (TBX15-WARS2, GRB14, ADAMTS9, LY86, RSPO3, ITPR2-SSPN). Further, we observed associations with metabolic traits: rs13389219 at GRB14 associated with HDL-cholesterol, triglycerides, and fasting insulin, and rs13060013 at ADAMTS9 with HDL-cholesterol and fasting insulin. Finally, we observed nominal evidence for sexual dimorphism, with stronger results in AA women at the GRB14 locus (p for interaction = 0.02). In conclusion, we identified two suggestive loci associated with fat distribution in AA populations in addition to confirming 6 loci previously identified in populations of EA. These findings reinforce the concept that there are fat distribution loci that are independent of generalized adiposity

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Binary systems and their nuclear explosions

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Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes