Recent Outbursts from the Transient X-Ray Pulsar Cep X-4 (GS 2138+56)

We report on X-ray observations of the 66 s period transient X-ray pulsar Cep X-4 (GS 2138+56) with the Burst and Transient Source Experiment (BATSE) on the Compton Gamma-Ray Observatory (CGRO) and with the Rossi X-ray Timing Explorer (RXTE). Two outbursts from Cep X-4 were observed with BATSE in 1993 June-July and 1997 July. Pulse frequencies of 15.0941 +/- 0.0002 mHz on 1993 June 25 (MJD 49,163) and 15.0882 +/- 0.0002 mHz on 1997 July 12 (MJD 50,641) were each measured from 2 day spans of BATSE data near each outburst's peak. Cep X-4 showed an average spin down rate of (-4.14 +/- 0.08)*10^(-14) Hz/s between the 1993 and 1997 outbursts. After BATSE could no longer detect Cep X-4, public observations were performed on 1997 July 18 & 25 with the Proportional Counter Array (PCA) on RXTE. A pulse frequency of 15.088 +/- 0.004 mHz was measured from observations on 1997 July 18 (MJD 50,647). Significant aperiodic noise, with an rms variance of ~18% in the frequency range 0.01-1.0 Hz was observed on both days. Energy and intensity dependent pulse shape variations were also seen in these data. Recently published optical observations associate Cep X-4 with a Be companion star. If all 4 outbursts observed from Cep X-4 are assumed to occur at the same orbital phase, we find that the orbital period is between 23 days and 147.3 days.Comment: 19 pages (LaTeX) including 9 figures. Accepted for publication in the Astrophysical Journa

Characterizing Inflow Conditions Across the Rotor Disk of a Utility-Scale Wind Turbine (Poster)

Multi-megawatt utility-scale wind turbines operate in a turbulent, thermally-driven atmosphere where wind speed and air temperature vary with height. Turbines convert the wind's momentum into electrical power, and so changes in the atmosphere across the rotor disk influence the power produced by the turbine. To characterize the inflow into utility scale turbines at the National Wind Technology Center (NWTC) near Boulder, Colorado, NREL recently built two 135-meter inflow monitoring towers. This poster introduces the towers and the measurements that are made, showing some of the data obtained in the first few months of operation in 2011

The Distribution of Redshifts in New Samples of Quasi-stellar Objects

Two new samples of QSOs have been constructed from recent surveys to test the hypothesis that the redshift distribution of bright QSOs is periodic in $\log(1+z)$. The first of these comprises 57 different redshifts among all known close pairs or multiple QSOs, with image separations $\leq$ 10\arcsec, and the second consists of 39 QSOs selected through their X-ray emission and their proximity to bright comparatively nearby active galaxies. The redshift distributions of the samples are found to exhibit distinct peaks with a periodic separation of $\sim 0.089$ in $\log(1+z)$ identical to that claimed in earlier samples but now extended out to higher redshift peaks $z = 2.63, 3.45$ and 4.47, predicted by the formula but never seen before. The periodicity is also seen in a third sample, the 78 QSOs of the 3C and 3CR catalogues. It is present in these three datasets at an overall significance level $10^{-5}$ - $10^{-6}$, and appears not to be explicable by spectroscopic or similar selection effects. Possible interpretations are briefly discussed.Comment: submitted for publication in the Astronomical Journal, 15 figure

The Stellar Population of h and chi Persei: Cluster Properties, Membership, and the Intrinsic Colors and Temperatures of Stars

(Abridged) From photometric observations of $\sim$ 47,000 stars and spectroscopy of $\sim$ 11,000 stars, we describe the first extensive study of the stellar population of the famous Double Cluster, h and $\chi$ Persei, down to subsolar masses. Both clusters have E(B-V) $\sim$ 0.52--0.55 and dM = 11.8--11.85; the halo population, while more poorly constrained, likely has identical properties. As determined from the main sequence turnoff, the luminosity of M supergiants, and pre-main sequence isochrones, ages for h Persei, $\chi$ Persei and the halo population all converge on $\approx$ 14 Myr. From these data, we establish the first spectroscopic and photometric membership lists of cluster stars down to early/mid M dwarfs. At minimum, there are $\sim$ 5,000 members within 10' of the cluster centers, while the entire h and $\chi$ Persei region has at least $\sim$ 13,000 and as many as 20,000 members. The Double Cluster contains $\approx$ 8,400 M$_{\odot}$ of stars within 10' of the cluster centers. We estimate a total mass of at least 20,000 M$_{\odot}$. We conclude our study by outlining outstanding questions regarding the properties of h and $\chi$ Persei. From comparing recent work, we compile a list of intrinsic colors and derive a new effective temperature scale for O--M dwarfs, giants, and supergiants.Comment: 88 pages, many figures, Accepted for publication in The Astrophysical Journal Supplements. Contact lead author for version with high-resolution figure

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Femtosecond tracking of carrier relaxation in germanium with extreme ultraviolet transient reflectivity

Extreme ultraviolet (XUV) transient reflectivity around the germanium M_(4,5) edge (3d core-level to valence transition) at 30 eV is advanced to obtain the transient dielectric function of crystalline germanium [100] on femtosecond to picosecond time scales following photoexcitation by broadband visible-to-infrared (VIS/NIR) pulses. By fitting the transient dielectric function, carrier-phonon induced relaxations are extracted for the excited carrier distribution. The measurements reveal a hot electron relaxation rate of 3.2 ± 0.2 ps attributed to the X−L intervalley scattering and a hot hole relaxation rate of 600 ± 300 fs ascribed to intravalley scattering within the heavy hole (HH) band, both in good agreement with previous work. An overall energy shift of the XUV dielectric function is assigned to a thermally induced band gap shrinkage by formation of acoustic phonons, which is observed to be on a timescale of 4–5 ps, in agreement with previously measured optical phonon lifetimes. The results reveal that the transient reflectivity signal at an angle of 66° with respect to the surface normal is dominated by changes to the real part of the dielectric function, due to the near critical angle of incidence of the experiment (66°–70°) for the range of XUV energies used. This work provides a methodology for interpreting XUV transient reflectivity near core-level transitions, and it demonstrates the power of the XUV spectral region for measuring ultrafast excitation dynamics in solids

Femtosecond tracking of carrier relaxation in germanium with extreme ultraviolet transient reflectivity

Extreme ultraviolet (XUV) transient reflectivity around the germanium M_(4,5) edge (3d core-level to valence transition) at 30 eV is advanced to obtain the transient dielectric function of crystalline germanium [100] on femtosecond to picosecond time scales following photoexcitation by broadband visible-to-infrared (VIS/NIR) pulses. By fitting the transient dielectric function, carrier-phonon induced relaxations are extracted for the excited carrier distribution. The measurements reveal a hot electron relaxation rate of 3.2 ± 0.2 ps attributed to the X−L intervalley scattering and a hot hole relaxation rate of 600 ± 300 fs ascribed to intravalley scattering within the heavy hole (HH) band, both in good agreement with previous work. An overall energy shift of the XUV dielectric function is assigned to a thermally induced band gap shrinkage by formation of acoustic phonons, which is observed to be on a timescale of 4–5 ps, in agreement with previously measured optical phonon lifetimes. The results reveal that the transient reflectivity signal at an angle of 66° with respect to the surface normal is dominated by changes to the real part of the dielectric function, due to the near critical angle of incidence of the experiment (66°–70°) for the range of XUV energies used. This work provides a methodology for interpreting XUV transient reflectivity near core-level transitions, and it demonstrates the power of the XUV spectral region for measuring ultrafast excitation dynamics in solids

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

Ursolic Acid Increases Skeletal Muscle and Brown Fat and Decreases Diet-Induced Obesity, Glucose Intolerance and Fatty Liver Disease

Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness

Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS

In contrast to cutaneous melanoma, there is no evidence that BRAF mutations are involved in the activation of the mitogen-activated protein kinase (MAPK) pathway in uveal melanoma, although there is increasing evidence that this pathway is activated frequently in the latter tumours. In this study, we performed mutation analysis of the RAS and BRAF genes in a panel of 11 uveal melanoma cell lines and 19 primary uveal melanoma tumours. In addition, Western blot and immunohistochemical analyses were performed on downstream members of the MAPK pathway in order to assess the contribution of each of these components. No mutations were found in any of the three RAS gene family members and only one cell line carried a BRAF mutation (V599E). Despite this, mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), ERK and ELK were constitutively activated in all samples. These data suggest that activation of the MAPK pathway is commonly involved in the development of uveal melanoma, but occurs through a mechanism different to that of cutaneous melanoma