The ACS Survey of Galactic Globular Clusters: M54 and Young Populations in the Sagittarius Dwarf Spheroidal Galaxy

We present new Hubble Space Telescope photometry of the massive globular cluster M54 (NGC 6715) and the superposed core of the tidally disrupted Sagittarius (Sgr) dSph galaxy as part of the ACS Survey of Galactic Globular Clusters. Our deep (F606W~26.5), high-precision photometry yields an unprecedentedly detailed color-magnitude diagram showing the extended blue horizontal branch and multiple main sequences of the M54+Sgr system. The distance and reddening to M54 are revised usingboth isochrone and main-sequence fitting to (m-M)_0=17.27 and E(B-V)=0.15. Preliminary assessment finds the M54+Sgr field to be dominated by the old metal-poor populations of Sgr and the globular cluster. Multiple turnoffs indicate the presence of at least two intermediate-aged star formation epochs with 4 and 6 Gyr ages and [Fe/H]=-0.4 to -0.6. We also clearly show, for the first time, a prominent, 2.3 Gyr old Sgr population of near-solar abundance. A trace population of even younger (0.1-0.8 Gyr old), more metal-rich ([Fe/H]\sim0.6) stars is also indicated. The Sgr age-metallicity relation is consistent with a closed-box model and multiple (4-5) star formation bursts over the entire life of the satellite, including the time since Sgr began disrupting.Comment: Accepted to ApJ Letter; 11 pages, 2 figures; figure 1 uploaded as jpg; paper in ApJ format with full-resolution figures available at: http://www.astro.ufl.edu/~ata/public_hstgc/paperIV/paperIV.p

The ACS Survey Of Galactic Globular Clusters. VI. NGC 6366: A Heavily Stripped Galactic Globular Cluster

We have used observations obtained as part of the Hubble Space Telescope/ACS Survey of Galactic globular clusters (GCs) to construct a color-magnitude diagram for the bulge cluster, NGC 6366. The luminosity function derived from those data extends to M(F606W) similar to 9, or masses of similar to 0.3 M(circle dot). Unlike most GCs, the mass function peaks near the main-sequence turnoff with significantly fewer low-mass stars even after correction for completeness and mass segregation. Using a multimass King model, we extrapolate the global cluster behavior and find the global mass function to be poorly matched by a power law, with a particular deficit of stars with masses between 0.5 and 0.7 M(circle dot). We briefly discuss this interesting anomaly within the context of tidal stripping.NASA GO-10775, 5-26555Space Telescope Science InstituteInstituto de Astrofisica de Canarias P3-94Ministry of Education and Science of the Kingdom of Spain AYA-2008-67913Astronom

A whole blood gene expression-based signature for smoking status

BACKGROUND: Smoking is the leading cause of preventable death worldwide and has been shown to increase the risk of multiple diseases including coronary artery disease (CAD). We sought to identify genes whose levels of expression in whole blood correlate with self-reported smoking status. METHODS: Microarrays were used to identify gene expression changes in whole blood which correlated with self-reported smoking status; a set of significant genes from the microarray analysis were validated by qRT-PCR in an independent set of subjects. Stepwise forward logistic regression was performed using the qRT-PCR data to create a predictive model whose performance was validated in an independent set of subjects and compared to cotinine, a nicotine metabolite. RESULTS: Microarray analysis of whole blood RNA from 209 PREDICT subjects (41 current smokers, 4 quit ≤ 2 months, 64 quit > 2 months, 100 never smoked; NCT00500617) identified 4214 genes significantly correlated with self-reported smoking status. qRT-PCR was performed on 1,071 PREDICT subjects across 256 microarray genes significantly correlated with smoking or CAD. A five gene (CLDND1, LRRN3, MUC1, GOPC, LEF1) predictive model, derived from the qRT-PCR data using stepwise forward logistic regression, had a cross-validated mean AUC of 0.93 (sensitivity=0.78; specificity=0.95), and was validated using 180 independent PREDICT subjects (AUC=0.82, CI 0.69-0.94; sensitivity=0.63; specificity=0.94). Plasma from the 180 validation subjects was used to assess levels of cotinine; a model using a threshold of 10 ng/ml cotinine resulted in an AUC of 0.89 (CI 0.81-0.97; sensitivity=0.81; specificity=0.97; kappa with expression model = 0.53). CONCLUSION: We have constructed and validated a whole blood gene expression score for the evaluation of smoking status, demonstrating that clinical and environmental factors contributing to cardiovascular disease risk can be assessed by gene expression

Orbits of Globular Clusters in the Outer Galaxy: NGC 7006

We present a proper motion study of the distant globular cluster NGC 7006 based on the measurement of 25 photographic plates spanning a 40-year interval. The absolute proper motion determined with respect to extragalactic objects is (-0.96, -1.14) +- (0.35, 0.40) mas/yr. The total space velocity of NGC 7006 in a Galactocentric rest frame is 279 km/s, placing the cluster on one of the most energetic orbits (Ra =102 kpc) known to date for clusters within 40-kpc from the Galactic center. We compare the orbits of four clusters that have apocentric radii larger than 80 kpc (NGC 5466, NGC 6934, NGC 7006 and Pal 13) with those of Galactic satellites with well-measured proper motions. These clusters have orbits that are highly eccentric and of various inclinations with respect to the Galactic plane. In contrast, the orbits of the Galactic satellites are of low to moderate eccentricity and highly inclined. Based on orbit types, chemical abundances and cluster parameters, we discuss the properties of the hypothetical host systems of the remote globular clusters in the Searle-Zinn paradigm. It is apparent that clusters such as NGC 5466, NGC 6934 and NGC 7006 formed in systems that more likely resemble the Fornax dSph, rather than the Sagittarius dSph. We also discuss plausible causes for the difference found so far between the orbit type of outer halo clusters and that of Galactic satellites and for the tentative, yet suggestive phase-space scatter found among outer halo clusters.Comment: 27 pages, 5 figures, to be published in the Astronomical Journa

Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8(+) T cells

Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8(+) T cells, but the specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination of CD4(+)CD25(+) regulatory T (T reg) cells has been proposed as a key mechanism by which lymphodepletion augments ACT-based immunotherapy. We found that even in the genetic absence of T reg cells, a nonmyeloablative regimen substantially augmented CD8(+) T cell reactivity to self-tissue and tumor. Surprisingly, enhanced antitumor efficacy and autoimmunity was caused by increased function rather than increased numbers of tumor-reactive T cells, as would be expected by homeostatic mechanisms. The γ (C) cytokines IL-7 and IL-15 were required for augmenting T cell functionality and antitumor activity. Removal of γ (C) cytokine–responsive endogenous cells using antibody or genetic means resulted in the enhanced antitumor responses similar to those seen after nonmyeloablative conditioning. These data indicate that lymphodepletion removes endogenous cellular elements that act as sinks for cytokines that are capable of augmenting the activity of self/tumor-reactive CD8(+) T cells. Thus, the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells