LNK suppresses interferon signaling in melanoma.

LNK (SH2B3) is a key negative regulator of JAK-STAT signaling which has been extensively studied in malignant hematopoietic diseases. We found that LNK is significantly elevated in cutaneous melanoma; this elevation is correlated with hyperactive signaling of the RAS-RAF-MEK pathway. Elevated LNK enhances cell growth and survival in adverse conditions. Forced expression of LNK inhibits signaling by interferon-STAT1 and suppresses interferon (IFN) induced cell cycle arrest and cell apoptosis. In contrast, silencing LNK expression by either shRNA or CRISPR-Cas9 potentiates the killing effect of IFN. The IFN-LNK signaling is tightly regulated by a negative feedback mechanism; melanoma cells exposed to IFN upregulate expression of LNK to prevent overactivation of this signaling pathway. Our study reveals an unappreciated function of LNK in melanoma and highlights the critical role of the IFN-STAT1-LNK signaling axis in this potentially devastating disease. LNK may be further explored as a potential therapeutic target for melanoma immunotherapy

Intracluster medium of the merging cluster Abell 3395

We present a detailed imaging and spectral analysis of the merging environment of the bimodal cluster A3395 using X-ray and radio observations. X-ray images of the cluster show five main constituents of diffuse emission : A3395 NE, A3395 SW, A3395 NW, A3395 W, and a filament connecting NE to W. X-ray surface-brightness profiles of the cluster did not show any shock fronts in the cluster. Temperature and entropy maps show high temperature and high entropy regions in the W, the NW, the filament and between the NE and SW subclusters. The NE, SW and W components have X-ray bolometric luminosities similar to those of rich clusters of galaxies but have relatively higher temperatures. Similarly, the NW component has X-ray bolometric luminosity similar to that of isolated groups but with much higher temperature. It is, therefore, possible that all the components of the cluster have been heated by the ongoing mergers. The NE subcluster is the most massive and luminous constituent and other subclusters are found to be gravitationally bound to it. The W component is most probably either a clump of gas stripped off the SW due to ram pressure or a separate subcluster that has merged or is merging with the SW. No X-ray cavities are seen associated with the Wide Angle Tailed (WAT) radio source near the centre of the SW subcluster. Minimum energy pressure in the radio emission-peaks of the WAT galaxy is comparable with the external thermal pressure. The radio spectrum of the WAT suggests a spectral age of ~10Myr

Chandra Observations of the Cl1604 Supercluster at z=0.9: Evidence for an Overdensity of Active Galactic Nuclei

We present the results of Chandra observations of the Cl1604 supercluster at z~0.9. The system is the largest structure mapped at redshifts approaching unity, containing at least eight spectroscopically confirmed galaxy clusters and groups. Using two 50-ksec ACIS-I pointings we examine both the X-ray point source population and the diffuse emission from individual clusters in the system. We find a 2.5\sigma excess of point sources detected in the hard band (2-10 keV) relative to the number of sources found in blank fields observed by Chandra. No such excess is observed in the soft band (0.5-2 keV). The hard-band source density is 1.47 times greater than that of a blank field, in agreement with the previously reported correlation between overdensity amplitude and cluster redshift. Using a maximum likelihood technique we have matched 112 of the 161 detected X-ray point sources to optical counterparts and found 15 sources that are associated with the supercluster. All 15 sources have rest-frame luminosities consistent with emission from active galactic nuclei (AGN). We find that the supercluster AGN largely avoid the densest regions of the system and are instead distributed on the outskirts of massive clusters or within poorer clusters and groups. We have also detected diffuse emission from two of the eight clusters and groups in the system, clusters Cl1604+4304 and Cl1604+4314. The systems have bolometric luminosities of 1.43x10^44 and 8.20x10^43 h70^-2 erg s^-1 and gas temperatures of 3.50 (+1.82-1.08) and 1.64 (+0.65-0.45) keV, respectively. Using updated velocity dispersions, we compare the properties of these systems to the cluster scaling relations followed by other X-ray and optically selected galaxy clusters at high redshift.Comment: 24 pages, 14 figures, submitted to Ap

Primordial Trispectrum from Entropy Perturbations in Multifield DBI Model

We investigate the primordial trispectra of the general multifield DBI inflationary model. In contrast with the single field model, the entropic modes can source the curvature perturbations on the super horizon scales, so we calculate the contributions from the interaction of four entropic modes mediating one adiabatic mode to the trispectra, at the large transfer limit ($T_{RS}\gg1$). We obtained the general form of the 4-point correlation functions, plotted the shape diagrams in two specific momenta configurations, "equilateral configuration" and "specialized configuration". Our figures showed that we can easily distinguish the two different momenta configurations.Comment: 17pages, 7 figures, version to appear in JCA

The CDEX-1 1 kg Point-Contact Germanium Detector for Low Mass Dark Matter Searches

The CDEX Collaboration has been established for direct detection of light dark matter particles, using ultra-low energy threshold p-type point-contact germanium detectors, in China JinPing underground Laboratory (CJPL). The first 1 kg point-contact germanium detector with a sub-keV energy threshold has been tested in a passive shielding system located in CJPL. The outputs from both the point-contact p+ electrode and the outside n+ electrode make it possible to scan the lower energy range of less than 1 keV and at the same time to detect the higher energy range up to 3 MeV. The outputs from both p+ and n+ electrode may also provide a more powerful method for signal discrimination for dark matter experiment. Some key parameters, including energy resolution, dead time, decay times of internal X-rays, and system stability, have been tested and measured. The results show that the 1 kg point-contact germanium detector, together with its shielding system and electronics, can run smoothly with good performances. This detector system will be deployed for dark matter search experiments.Comment: 6 pages, 8 figure

Astrometric Microlensing by Local Dark Matter Subhalos

High-resolution N-body simulations of dark matter halos indicate that the Milky Way contains numerous subhalos. When a dark matter subhalo passes in front of a star, the light from that star will be deflected by gravitational lensing, leading to a small change in the star's apparent position. This astrometric microlensing signal depends on the inner density profile of the subhalo and can be greater than a few microarcseconds for an intermediate-mass subhalo (Mvir > 10000 solar masses) passing within arcseconds of a star. Current and near-future instruments could detect this signal, and we evaluate SIM's, Gaia's, and ground-based telescopes' potential as subhalo detectors. We develop a general formalism to calculate a subhalo's astrometric lensing cross section over a wide range of masses and density profiles, and we calculate the lensing event rate by extrapolating the subhalo mass function predicted by simulations down to the subhalo masses potentially detectable with this technique. We find that, although the detectable event rates are predicted to be low on the basis of current simulations, lensing events may be observed if the central regions of dark matter subhalos are more dense than current models predict (>1 solar mass within 0.1 pc of the subhalo center). Furthermore, targeted astrometric observations can be used to confirm the presence of a nearby subhalo detected by gamma-ray emission. We show that, for sufficiently steep density profiles, ground-based adaptive optics astrometric techniques could be capable of detecting intermediate-mass subhalos at distances of hundreds of parsecs, while SIM could detect smaller and more distant subhalos.Comment: 18 pages, 8 figures, minor revisions made to match version to appear in Ap

Ontogeny and thermogenic role for sternal fat in female sheep

Brown adipose tissue acting through a unique uncoupling protein (UCP1) has a critical role in preventing hypothermia in new-born sheep but is then considered to rapidly disappear during postnatal life. The extent to which the anatomical location of fat influences postnatal development and thermogenic function, particularly following feeding, in adulthood, are not known and were both examined in our study. Changes in gene expression of functionally important pathways (i.e. thermogenesis, development, adipogenesis and metabolism) were compared between sternal and retroperitoneal fat depots together with a representative skeletal muscle over the first month of postnatal life, coincident with the loss of brown fat and accumulation of white fat. In adult sheep, implanted temperature probes were used to characterise the thermogenic response of fat and muscle to feeding and the effects of reduced or increased adiposity. UCP1 was more abundant within sternal than retroperitoneal fat and was only retained in the sternal depot of adults. Distinct differences in the abundance of gene pathway markers were apparent between tissues, with sternal fat exhibiting some similarities with muscle that were not apparent in the retroperitoneal depot. In adults, the post-prandial rise in temperature was greater and more prolonged in sternal than retroperitoneal fat and muscle, a difference that was maintained with altered adiposity. In conclusion, sternal adipose tissue retains UCP1 into adulthood when it shows a greater thermogenic response to feeding than muscle and retroperitoneal fat. Sternal fat may be more amenable to targeted interventions that promote thermogenesis in large mammals

Factors associated with mobile health information seeking among Singaporean women

This study examined effects of age and social psychological factors on women’s willingness to be mobile health information seekers. A national survey of 1,878 Singaporean women was conducted to obtain information on women’s mobile phone usage, experiences of health information seeking, and appraisals of using mobile phones to seek health information. Results showed that young, middle-aged, and older women exhibited distinct mobile phone usage behaviors, health information-seeking patterns, and assessments of mobile health information seeking. Factors that accounted for their mobile information-seeking intention also varied. Data reported in this study provide insights into mobile health interventions in the future

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations