Line Broadening in Field Metal-poor Red Giant and Red Horizontal Branch Stars

We report 349 radial velocities for 45 metal-poor field red giant and red horizontal branch stars. We have have identified one new spectroscopic binary, HD 4306, and one possible such system, HD 184711. We also report 57 radial velocities for 11 of the 91 stars reported on previously by Carney et al. (2003). As was found in the previous study, radial velocity "jitter" is present in many of the most luminous stars. Excluding stars showing spectroscopic binary orbital motion, all 7 of the red giants with M(V) <= -2.0 display jitter, as well as 3 of the 14 stars with -2.0 <= M(V) <= -1.4. We have also measured line broadening in all of the new spectra, using synthetic spectra as templates. The most luminous red giants show significant line broadening, as do many of the red horizontal branch stars, and we discuss briefly possible causes.Comment: To appear in the Astronomical Journa

The Stellar Population of the M31 Spiral Arm Around OB Association A24

A study of the stellar population of the M31 spiral arm around OB association A24 was carried out based on the photometric data obtained from deep V and JHK imaging. The luminosity function was obtained for -7 <~ Mbol <~ -3.5 by applying the extinction correction corresponding to Av=1 and the bolometric correction BC(K) as an empirical function of (J-K)o. In comparing the observed color-luminosity diagrams with semitheoretical isochrones modified for the dust-shell effects, we found the young population of t <~ 30 Myr with supergiants of Mbol <~ -5, the bulk of the intermediate-age population of t ~ 0.2 - 2.5 Gyr with bright asymptotic giant branch (AGB) stars of -5 <~ Mbol <~ -4, and old populations of t ~> 3 Gyr with AGB and red giant branch (RGB) stars of Mbol ~> -4. The average star formation rate was estimated to be ~1.8x10^4 M_o/Myr and ~0.7x10^4 M_o/Myr per deprojected disk area of 1 kpc^2 from the number density of B0 V stars around Mv=-4.0 (age ~10 Myr) and the number density of bright AGB stars around Mbol = -4.3 (age ~1 Gyr), respectively. A study of the local variation in the V and the J and H luminosity functions revealed a kind of anticorrelation between the population of the young component and that of the intermediate-age component when subdomains of ~100 pc scales were concerned. This finding suggests that the disk domain around the A24 area experienced a series of star formation episodes alternatively among different subdomains with a timescale of a few spiral passage periods. Brief discussions are given about the interstellar extinction and about the lifetimes of bright AGB stars and the highly red objects (HROs) in the same area.Comment: 27 pages, 11 figures, accepted: ApJ, July 1, 199

BCR-ABL induces the expression of Skp2 through the PI3K pathway to promote p27Kip1 degradation and proliferation of chronic myelogenous leukemia cells

Chronic myelogenous leukemia (CML) is characterized by the expression of the BCR-ABL tyrosine kinase, which results in increased cell proliferation and inhibition of apoptosis. In this study, we show in both BCR-ABL cells (Mo7e-p210 and BaF/3-p210) and primary CML CD34+ cells that STI571 inhibition of BCR-ABL tyrosine kinase activity results in a G(1) cell cycle arrest mediated by the PI3K pathway. This arrest is associated with a nuclear accumulation of p27(Kip1) and down-regulation of cyclins D and E. As a result, there is a reduction of the cyclin E/Cdk2 kinase activity and of the retinoblastoma protein phosphorylation. By quantitative reverse transcription-PCR we show that BCR-ABL/PI3K regulates the expression of p27(Kip1) at the level of transcription. We further show that BCR-ABL also regulates p27(Kip1) protein levels by increasing its degradation by the proteasome. This degradation depends on the ubiquitinylation of p27(Kip1) by Skp2-containing SFC complexes: silencing the expression of Skp2 with a small interfering RNA results in the accumulation of p27(Kip1). We also demonstrate that BCR-ABL cells show transcriptional up-regulation of Skp2. Finally, expression of a p27(Kip1) mutant unable of being recognized by Skp2 results in inhibition of proliferation of BCR-ABL cells, indicating that the degradation of p27(Kip1) contributes to the pathogenesis of CML. In conclusion, these results suggest that BCR-ABL regulates cell cycle in CML cells at least in part by inducing proteasome-mediated degradation of the cell cycle inhibitor p27(Kip1) and provide a rationale for the use of inhibitors of the proteasome in patients with BCR-ABL leukemias

High-Resolution Spectroscopy of the Transiting Planet Host Star TrES-1

We report on a spectroscopic determination of the stellar parameters and chemical abundances for the parent star of the transiting planet TrES-1. Based on a detailed analysis of iron lines in our Keck and HET spectra we derive $T_\mathrm{eff} = 5250\pm 75$ K, $\log g = 4.6\pm 0.2$, and [Fe/H] $= 0.00\pm 0.09$. By measuring the \ion{Ca}{2} activity indicator and by putting useful upper limits on the Li abundance we constrain the age of TrES-1 to be $2.5\pm 1.5$ Gyr. By comparing theoretical stellar evolution models with the observational parameters we obtain $M_\star = 0.89\pm 0.05$ $M_\odot$, and $R_\star = 0.83\pm 0.05$ $R_\odot$. Our improved estimates of the stellar parameters are utilized in a new analysis of the transit photometry of TrES-1 to derive a mass $M_p = 0.76\pm 0.05$ $M_\mathrm{J}$, a radius $R_p = 1.04^{+0.08}_{-0.05}$ $R_\mathrm{J}$, and an inclination $i = 89^\circ.5^{+0.5}_{-1.3}$. The improved planetary mass and radius estimates provide the grounds for new crucial tests of theoretical models of evolution and evaporation of irradiated extrasolar giant planets.Comment: 14 pages, 3 figures, Astrophysical Journal Letters, accepte

Virological and immunological outcome of treatment interruption in HIV-1-infected subjects vaccinated with MVA-B

The most relevant endpoint in therapeutic HIV vaccination is the assessment of time to viral rebound or duration of sustained control of low-level viremia upon cART treatment cessation. Structured treatment interruptions (STI) are however not without risk to the patient and reliable predictors of viral rebound/control after therapeutic HIV-1 vaccination are urgently needed to ensure patient safety and guide therapeutic vaccine development. Here, we integrated immunological and virological parameters together with viral rebound dynamics after STI in a phase I therapeutic vaccine trial of a polyvalent MVA-B vaccine candidate to define predictors of viral control. Clinical parameters, proviral DNA, host HLA genetics and measures of humoral and cellular immunity were evaluated. A sieve effect analysis was conducted comparing pre-treatment viral sequences to breakthrough viruses after STI. Our results show that a reduced proviral HIV-1 DNA at study entry was independently associated with two virological parameters, delayed HIV-1 RNA rebound (p = 0.029) and lower peak viremia after treatment cessation (p = 0.019). Reduced peak viremia was also positively correlated with a decreased number of HLA class I allele associated polymorphisms in Gag sequences in the rebounding virus population (p = 0.012). Our findings suggest that proviral DNA levels and the number of HLA-associated Gag polymorphisms may have an impact on the clinical outcome of STI. Incorporation of these parameters in future therapeutic vaccine trials may guide refined immunogen design and help conduct safer STI approaches

The effective temperature scale of FGK stars. II. Teff : color : [Fe/H] calibrations

We present up-to-date metallicity-dependent temperature vs. color calibrations for main sequence and giant stars based on temperatures derived with the infrared flux method (IRFM). Seventeen colors in the following photometric systems: UBV, uvby, Vilnius, Geneva, RI(Cousins), DDO, Hipparcos-Tycho, and 2MASS, have been calibrated. The spectral types covered range from F0 to K5 (7000 K<Teff<4000 K) with some relations extending below 4000 K or up to 8000 K. Most of the calibrations are valid in the metallicity range -3.5<[Fe/H]<0.4, although some of them extend to as low as [Fe/H]=-4.0. All fits to the data have been performed with more than 100 stars; standard deviations range from 30 K to 120 K. Fits were carefully performed and corrected to eliminate the small systematic errors introduced by the calibration formulae. Tables of colors as a function of Teff and [Fe/H] are provided. (Abridged)Comment: To appear in ApJ. For online tables and figures, see http://webspace.utexas.edu/ir68/tef

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.Peer reviewe

Telomere fusion threshold identifies a poor prognostic subset of breast cancer patients

Telomere dysfunction and fusion can drive genomic instability and clonal evolution in human tumours, including breast cancer. Telomere length is a critical determinant of telomere function and has been evaluated as a prognostic marker in several tumour types, but it has yet to be used in the clinical setting. Here we show that high-resolution telomere length analysis, together with a specific telomere fusion threshold, is highly prognostic for overall survival in a cohort of patients diagnosed with invasive ductal carcinoma of the breast (n = 120). The telomere fusion threshold defined a small subset of patients with an extremely poor clinical outcome, with a median survival of less than 12 months (HR = 21.4 (7.9-57.6), P < 0.0001). Furthermore, this telomere length threshold was independent of ER, PGR, HER2 status, NPI, or grade and was the dominant variable in multivariate analysis. We conclude that the fusogenic telomere length threshold provides a powerful, independent prognostic marker with clinical utility in breast cancer. Larger prospective studies are now required to determine the optimal way to incorporate high-resolution telomere length analysis into multivariate prognostic algorithms for patients diagnosed with breast cancer

C.E.R.A. once every 4 weeks corrects anaemia and maintains haemoglobin in patients with chronic kidney disease not on dialysis

Background. No previous randomized controlled studies have been reported examining de novo, once every 4 weeks (Q4W) administration of erythropoiesis-stimulating agents in chronic kidney disease (CKD) patients. We report results from a randomized multinational study that compared continuous erythropoietin receptor activator (C.E.R.A.) Q4W with darbepoetin alfa once weekly (QW) or every 2 weeks (Q2W) for the correction of anaemia in non-dialysis CKD patients