Mapping the Galactic disk with the LAMOST and Gaia Red clump sample: I: precise distances, masses, ages and 3D velocities of ∼\sim 140000 red clump stars

We present a sample of $\sim$ 140,000 primary red clump (RC) stars of spectral signal-to-noise ratios higher than 20 from the LAMOST Galactic spectroscopic surveys, selected based on their positions in the metallicity-dependent effective temperature--surface gravity and color--metallicity diagrams, supervised by high-quality $Kepler$ asteroseismology data. The stellar masses and ages of those stars are further determined from the LAMOST spectra, using the Kernel Principal Component Analysis method, trained with thousands of RCs in the LAMOST-$Kepler$ fields with accurate asteroseismic mass measurements. The purity and completeness of our primary RC sample are generally higher than 80 per cent. For the mass and age, a variety of tests show typical uncertainties of 15 and 30 per cent, respectively. Using over ten thousand primary RCs with accurate distance measurements from the parallaxes of Gaia DR2, we re-calibrate the $K_{\rm s}$ absolute magnitudes of primary RCs by, for the first time, considering both the metallicity and age dependencies. With the the new calibration, distances are derived for all the primary RCs, with a typical uncertainty of 5--10 per cent, even better than the values yielded by the Gaia parallax measurements for stars beyond 3--4 kpc. The sample covers a significant volume of the Galactic disk of $4 \leq R \leq 16$ kpc, $|Z| \leq 5$ kpc, and $-20 \leq \phi \leq 50^{\circ}$. Stellar atmospheric parameters, line-of-sight velocities and elemental abundances derived from the LAMOST spectra and proper motions of Gaia DR2 are also provided for the sample stars. Finally, the selection function of the sample is carefully evaluated in the color-magnitude plane for different sky areas. The sample is publicly available.Comment: 16 pages, 19 figures, 3 tables, accepted for publication in ApJ

The SSS phase of RS Ophiuchi observed with Chandra and XMM-Newton I.: Data and preliminary Modeling

The phase of Super-Soft-Source (SSS) emission of the sixth recorded outburst of the recurrent nova RS Oph was observed twice with Chandra and once with XMM-Newton. The observations were taken on days 39.7, 54.0, and 66.9 after outburst. We confirm a 35-sec period on day 54.0 and found that it originates from the SSS emission and not from the shock. We discus the bound-free absorption by neutral elements in the line of sight, resonance absorption lines plus self-absorbed emission line components, collisionally excited emission lines from the shock, He-like intersystem lines, and spectral changes during an episode of high-amplitude variability. We find a decrease of the oxygen K-shell absorption edge that can be explained by photoionization of oxygen. The absorption component has average velocities of -1286+-267 km/s on day 39.7 and of -771+-65 km/s on day 66.9. The wavelengths of the emission line components are consistent with their rest wavelengths as confirmed by measurements of non-self absorbed He-like intersystem lines. We have evidence that these lines originate from the shock rather than the outer layers of the outflow and may be photoexcited in addition to collisional excitations. We found collisionally excited emission lines that are fading at wavelengths shorter than 15A that originate from the radiatively cooling shock. On day 39.5 we find a systematic blue shift of -526+-114 km/s from these lines. We found anomalous He-like f/i ratios which indicates either high densities or significant UV radiation near the plasma where the emission lines are formed. During the phase of strong variability the spectral hardness light curve overlies the total light curve when shifted by 1000sec. This can be explained by photoionization of neutral oxygen in the line of sight if the densities of order 10^{10}-10^{11} cm^{-3}.Comment: 16 pages, 10 figures, 4 tables. Accepted by ApJ; v2: Co-author Woodward adde

Development of a Human Cytomegalovirus (HCMV)-Based Therapeutic Cancer Vaccine Uncovers a Previously Unsuspected Viral Block of MHC Class I Antigen Presentation

Human cytomegalovirus (HCMV) induces a uniquely high frequency of virus-specific effector/memory CD8+ T-cells, a phenomenon termed “memory inflation”. Thus, HCMV-based vaccines are particularly interesting in order to stimulate a sustained and strong cellular immune response against cancer. Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor with high lethality and inevitable relapse. The current standard treatment does not significantly improve the desperate situation underlining the urgent need to develop novel approaches. Although HCMV is highly fastidious with regard to species and cell type, GBM cell lines are susceptible to HCMV. In order to generate HCMV-based therapeutic vaccine candidates, we deleted all HCMV-encoded proteins (immunoevasins) that interfere with MHC class I presentation. The aim being to use the viral vector as an adjuvant for presentation of endogenous tumor antigens, the presentation of high levels of vector-encoded neoantigens and finally the repurposing of bystander HCMV-specific CD8+ T cells to fight the tumor. As neoantigen, we exemplarily used the E6 and E7 proteins of human papillomavirus type 16 (HPV-16) as a non-transforming fusion protein (E6/E7) that covers all relevant antigenic peptides. Surprisingly, GBM cells infected with E6/E7-expressing HCMV-vectors failed to stimulate E6-specific T cells despite high level expression of E6/E7 protein. Further experiments revealed that MHC class I presentation of E6/E7 is impaired by the HCMV-vector although it lacks all known immunoevasins. We also generated HCMV-based vectors that express E6-derived peptide fused to HCMV proteins. GBM cells infected with these vectors efficiently stimulated E6-specific T cells. Thus, fusion of antigenic sequences to HCMV proteins is required for efficient presentation via MHC class I molecules during infection. Taken together, these results provide the preclinical basis for development of HCMV-based vaccines and also reveal a novel HCMV-encoded block of MHC class I presentation

The K2 Galactic Archaeology Program Data Release 2: Asteroseismic Results from Campaigns 4, 6, and 7

Studies of Galactic structure and evolution have benefited enormously from Gaia kinematic information, though additional, intrinsic stellar parameters like age are required to best constrain Galactic models. Asteroseismology is the most precise method of providing such information for field star populations en masse, but existing samples for the most part have been limited to a few narrow fields of view by the CoRoT and Kepler missions. In an effort to provide well-characterized stellar parameters across a wide range in Galactic position, we present the second data release of red giant asteroseismic parameters for the K2 Galactic Archaeology Program (GAP). We provide V_{max} and Delta_{v} based on six independent pipeline analyses; first-ascent red giant branch (RGB) and red clump (RC) evolutionary state classifications from machine learning; and ready-to-use radius and mass coefficients, K_{R} and K_{M}, which, when appropriately multiplied by a solar-scaled effective temperature factor, yield physical stellar radii and masses. In total, we report 4395 radius and mass coefficients, with typical uncertainties of 3.3% (stat.) ± 1% (syst.) for K_{R} and 7.7% (stat.) ± 2% (syst.) for κM among RGB stars, and 5.0% (stat.) ± 1% (syst.) for K_{R} nd 10.5% (stat.) ± 2% (syst.) for κM among RC stars. We verify that the sample is nearly complete—except for a dearth of stars with V_{max} \leqslant 10-20 mHz-by comparing to Galactic models and visual inspection. Our asteroseismic radii agree with radii derived from Gaia Data Release 2 parallaxes to within 2.2% ± 0.3% for RGB stars and 2.0% ± 0.6% for RC stars

A Study of T Cell Tolerance to the Tumor-Associated Antigen MDM2: Cytokines Can Restore Antigen Responsiveness, but Not High Avidity T Cell Function

BACKGROUND: Most tumor-associated antigens (TAA) currently used for immunotherapy of cancer are also expressed in normal tissues, which may induce tolerance and impair T cell-mediated immunity. However, there is limited information about how physiological expression in normal tissues alters the function of TAA-specific T cells. METHODOLOGY/PRINCIPAL FINDINGS: We used a T cell receptor transgenic model to study how MDM2 expression in normal tissues affects the function of T cells specific for this TAA that is found at high levels in many different types of tumors. We found that some MDM2-specific T cells escaped thymic deletion and persisted in the peripheral T cell pool. When stimulated with antigen, these T cells readily initiated cell division but failed to proliferate and expand, which was associated with a high rate of apoptosis. Both IL-2 and IL-15 efficiently rescued T cell survival and antigen-specific T cell proliferation, while IL-7 and IL-21 were ineffective. Antigen-stimulated T cells showed impaired expression of the effector molecules CD43, granzyme-B and IFN-γ, a defect that was completely restored when T cells were stimulated in the presence of IL-2. In contrast, IL-15 and IL-21 only restored the expression of CD43 and granzyme-B, but not IFN-γ production. Finally, peptide titration experiments with IL-2 rescued T cells indicated that they were of lower avidity than non-tolerant control T cells expressing the same TCR. CONCLUSIONS/SIGNIFICANCE: These data indicate that cytokines can rescue the antigen-specific proliferation and effector function of MDM2-specific T cells, although this does not lead to the recovery of high avidity T cell function. This study sheds light on possible limitations of immunotherapy approaches that target widely expressed TAA, such as MDM2

The Dark Matter halo of the Milky Way, AD 2013

We derive the mass model of the Milky Way (MW) using a cored dark matter (DM) halo profile and recent data. The method used consists in fitting a spherically symmetric model of the Galaxy with a Burkert DM halo profile to available data: MW terminal velocities in the region inside the solar circle, circular velocity as recently estimated from maser star forming regions at intermediate radii, and velocity dispersions of stellar halo tracers for the outermost Galactic region. The latter are reproduced by integrating the Jeans equation for every modeled mass distribution, and by allowing for different velocity anisotropies for different tracer populations. For comparison we also consider a Navarro-Frenk-White profile. We find that the cored profile is the preferred one, with a shallow central density of rho_H~4x10^7M_s/kpc^3 and a large core radius R_H~10 kpc, as observed in external spirals and in agreement with the mass model underlying the Universal Rotation Curve of spirals. We describe also the derived model uncertainties, which are crucially driven by the poorly constrained velocity dispersion anisotropies of halo tracers. The emerging cored DM distribution has implications for the DM annihilation angular profile, which is much less boosted in the Galactic center direction with respect to the case of the standard \Lambda CDM, NFW profile. Using the derived uncertainties we discuss finally the limitations and prospects to discriminate between cored and cusped DM profile with a possible observed diffuse DM annihilation signal. The present mass model aims to characterize the present-day description of the distribution of matter in our Galaxy, which is needed to frame current crucial issues of Cosmology, Astrophysics and Elementary Particles

Itk Negatively Regulates Induction of T Cell Proliferation by CD28 Costimulation

CD28 is a cell surface molecule that mediates a costimulatory signal crucial for T cell proliferation and lymphokine production. The signal transduction mechanisms of CD28 are not well understood. Itk, a nonreceptor protein tyrosine kinase specifically expressed in T cells and mast cells, has been implicated in the CD28 signaling pathway because of reports that it becomes phosphorylated on tyrosines and associates with CD28 upon cross-linking of the cell surface molecule. To determine whether Itk plays a functional role in CD28 signaling, we compared T cells from Itk-deficient mice and control mice for their responses to CD28 costimulation. T cells defective in Itk were found to be fully competent to respond to costimulation. Whereas the CD3-mediated proliferative response was severely compromised in the absence of Itk, the calcineurin-independent CD28-mediated response was significantly elevated when compared with cells from control animals. The augmented proliferation was not due to increased production of interleukin-2. The results suggest that Itk has distinct roles in the CD3 versus the CD28 signaling pathways. By negatively regulating the amplitude of signaling upon CD28 costimulation, Itk may provide a means for modulating the outcome of T cell activation during development and during antigen-driven immune responses