Anomalous RR Lyrae stars(?). III. CM Leonis

Time series of B,V,I CCD photometry and radial velocity measurements from high resolution spectroscopy (R=30,000) covering the full pulsation cycle are presented for the field RR Lyrae star CM Leonis. The photometric data span a 6 year interval from 1994 to 1999, and allow us to firmly establish the pulsation mode and periodicity of the variable. The derived period P=0.361699 days (+/- 0.000001) is very close to the value published in the Fourth Edition of the General Catalogue of Variable Stars (P=0.361732 days). However, contrary to what was previously found, the amplitude and shape of the light curve qualify CM Leo as a very regular first overtone pulsator with a prominent hump on the rising branch of its multicolour light curves. According to an abundace analysis performed on three spectra taken near minimum light (0.42 < phase < 0.61), CM Leo is a metal-poor star with metal abundance [Fe/H]=-1.93 +/- 0.20. The photometric and radial velocity curves of CM Leo have been compared with the predictions of suitable pulsational models to infer tight constraints on the stellar mass, effective temperature, and distance modulus of the star. We derive a true distance modulus of CM Leo of (m-M)0=13.11 +/- 0.02 mag and a corresponding absolute magnitude of Mv=0.47 +/- 0.04. This absolute magnitude, once corrected for evolutionary and metallicity effects, leads to a true distance modulus of the Large Magellanic Cloud of (m-M)0=18.43 +/- 0.06 mag, in better agreement with the long astronomical distance scale.Comment: 14 pages, 10 figures, accepted for publication in MNRA

CU Comae: a new field double-mode RR Lyrae, the most metal poor discovered to date

We report the discovery of a new double-mode RR Lyrae variable (RRd) in the field of our Galaxy: CU Comae. CU Comae is the sixth such RRd identified to date and is the most metal-poor RRd ever detected. Based on BVI CCD photometry spanning eleven years of observations, we find that CU Comae has periods P0=0.5441641 +/-0.0000049d and P1=0.4057605 +/-0.0000018d. The amplitude of the primary (first-overtone) period of CU Comae is about twice the amplitude of the secondary (fundamental) period. The combination of the fundamental period of pulsation P0 and the period ratio of P1/P0=0.7457 places the variable on the metal-poor side of the Petersen diagram, in the region occupied by M68 and M15 RRd's. A mass of 0.83 solar masses is estimated for CU Comae using an updated theoretical calibration of the Petersen diagram. High resolution spectroscopy (R=30,000) covering the full pulsation cycle of CU Comae was obtained with the 2.7 m telescope of the Mc Donald Observatory, and has been used to build up the radial velocity curve of the variable. Abundance analysis done on the four spectra taken near minimum light (phase: 0.54 -- 0.71) confirms the metal poor nature of CU Comae, for which we derive [Fe/H]=-2.38 +/-0.20. This value places this new RRd at the extreme metal-poor edge of the metallicity distribution of the RR Lyrae variables in our Galaxy.Comment: 21 pages including 8 Tables, Latex, 11 Figures. Accepted for publication in The Astronomical Journal, October 2000 issu

Cancer-Initiating Cells from Colorectal cancer Patients Escape from T Cell-Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4

Cancer-initiating cells (CICs) that are responsible for tumor initiation, propagation, and resistance to standard therapies have been isolated from human solid tumors, including colorectal cancer (CRC). The aim of this study was to obtain an immunological profile of CRC-derived CICs and to identify CIC-associated target molecules for T cell immunotherapy. We have isolated cells with CIC properties along with their putative non-CIC autologous counterparts from human primary CRC tissues. These CICs have been shown to display “tumor-initiating/stemness” properties, including the expression of CIC-associated markers (e.g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenicity following injection in immunodeficient mice. The immune profile of these cells was assessed by phenotype analysis and by in vitro stimulation of PBMCs with CICs as a source of Ags. CICs, compared with non-CIC counterparts, showed weak immunogenicity. This feature correlated with the expression of high levels of immu- nomodulatory molecules, such as IL-4, and with CIC-mediated inhibitory activity for anti-tumor T cell responses. CIC-associated IL-4 was found to be responsible for this negative function, which requires cell-to-cell contact with T lymphocytes and which is impaired by blocking IL-4 signaling. In addition, the CRC-associated Ag COA-1 was found to be expressed by CICs and to represent, in an autologous setting, a target molecule for anti-tumor T cells. Our study provides relevant information that may contribute to designing new immunotherapy protocols to target CICs in CRC patient

Direct Evidence that Bevacizumab, an Anti-VEGF Antibody, Up-regulates SDF1 , CXCR4, CXCL6, and Neuropilin 1 in Tumors from Patients with Rectal Cancer

Clinical studies converge on the observation that circulating cytokines are elevated in most cancer patients by anti-vascular endothelial growth factor (VEGF) therapy. However, the source of these molecules and their relevance in tumor escape remain unknown. We examined the gene expression profiles of cancer cells and tumor-associated macrophages in tumor biopsies before and 12 days after monotherapy with the anti-VEGF antibody bevacizumab in patients with rectal carcinoma. Bevacizumab up-regulated stromal cell-derived factor 1alpha (SDF1alpha), its receptor CXCR4, and CXCL6, and down-regulated PlGF, Ang1, and Ang2 in cancer cells. In addition, bevacizumab decreased Ang1 and induced neuropilin 1 (NRP1) expression in tumor-associated macrophages. Higher SDF1alpha plasma levels during bevacizumab treatment significantly associated with distant metastasis at three years. These data show that VEGF blockade up-regulates inflammatory pathways and NRP1, which should be evaluated as potential targets for improving anti-VEGF therapy

Intrinsic and dust-induced polarization in gamma-ray burst afterglows: the case of GRB 021004

Polarization measurements for the optical counterpart to GRB 021004 are presented and discussed. Our observations were performed with the TNG and the VLT-UT3 (Melipal) during the first and fourth night after the gamma-ray burst discovery. We find robust evidence of temporal evolution of the polarization, which is therefore, at least partially, intrinsic to the optical transient. We do not find convincing evidence of wavelength dependence for the intrinsic polarization of the transient, in agreement with current polarization models for optical afterglows. We discuss the role of dust, both in our galaxy and in the host, in modifying the transmitted polarization vector, showing how a sizable fraction of the observed polarized flux is due to Galactic selective extinction, while it is not possible to single out any clear contribution from dust in the host galaxy. We discuss how our data compare to those obtained by different groups showing that a two-component model is required to describe the complete dataset. This is not surprising given the complex lightcurve of GRB 021004.Comment: 9 pages, 6 postscript figures, A&A in pres

PDGF-C Induces Maturation of Blood Vessels in a Model of Glioblastoma and Attenuates the Response to Anti-VEGF Treatment

Recent clinical trials of VEGF inhibitors have shown promise in the treatment of recurrent glioblastomas (GBM). However, the survival benefit is usually short-lived as tumors escape anti-VEGF therapies. Here we tested the hypothesis that Platelet Derived Growth Factor-C (PDGF-C), an isoform of the PDGF family, affects GBM progression independent of VEGF pathway and hinders anti-VEGF therapy.We first showed that PDGF-C is present in human GBMs. Then, we overexpressed or downregulated PDGF-C in a human GBM cell line, U87MG, and grew them in cranial windows in nude mice to assess vessel structure and function using intravital microscopy. PDGF-C overexpressing tumors had smaller vessel diameters and lower vascular permeability compared to the parental or siRNA-transfected tumors. Furthermore, vessels in PDGF-C overexpressing tumors had more extensive coverage with NG2 positive perivascular cells and a thicker collagen IV basement membrane than the controls. Treatment with DC101, an anti-VEGFR-2 antibody, induced decreases in vessel density in the parental tumors, but had no effect on the PDGF-C overexpressing tumors.These results suggest that PDGF-C plays an important role in glioma vessel maturation and stabilization, and that it can attenuate the response to anti-VEGF therapy, potentially contributing to escape from vascular normalization

Modeling dust mineralogical composition: sensitivity to soil mineralogy atlases and their expected climate impacts

Soil dust aerosols are a key component of the climate system, as they interact with short- and long-wave radiation, alter cloud formation processes, affect atmospheric chemistry and play a role in biogeochemical cycles by providing nutrient inputs such as iron and phosphorus. The influence of dust on these processes depends on its physicochemical properties, which, far from being homogeneous, are shaped by its regionally varying mineral composition. The relative amount of minerals in dust depends on the source region and shows a large geographical variability. However, many state-of-the-art Earth system models (ESMs), upon which climate analyses and projections rely, still consider dust mineralogy to be invariant. The explicit representation of minerals in ESMs is more hindered by our limited knowledge of the global soil composition along with the resulting size-resolved airborne mineralogy than by computational constraints. In this work we introduce an explicit mineralogy representation within the state-of-the-art Multiscale Online Nonhydrostatic AtmospheRe CHemistry (MONARCH) model. We review and compare two existing soil mineralogy datasets, which remain a source of uncertainty for dust mineralogy modeling and provide an evaluation of multiannual simulations against available mineralogy observations. Soil mineralogy datasets are based on measurements performed after wet sieving, which breaks the aggregates found in the parent soil. Our model predicts the emitted particle size distribution (PSD) in terms of its constituent minerals based on brittle fragmentation theory (BFT), which reconstructs the emitted mineral aggregates destroyed by wet sieving. Our simulations broadly reproduce the most abundant mineral fractions independently of the soil composition data used. Feldspars and calcite are highly sensitive to the soil mineralogy map, mainly due to the different assumptions made in each soil dataset to extrapolate a handful of soil measurements to arid and semi-arid regions worldwide. For the least abundant or more difficult-to-determine minerals, such as iron oxides, uncertainties in soil mineralogy yield differences in annual mean aerosol mass fractions of up to ∼ 100 %. Although BFT restores coarse aggregates including phyllosilicates that usually break during soil analysis, we still identify an overestimation of coarse quartz mass fractions (above 2 µm in diameter). In a dedicated experiment, we estimate the fraction of dust with undetermined composition as given by a soil map, which makes up ∼ 10 % of the emitted dust mass at the global scale and can be regionally larger. Changes in the underlying soil mineralogy impact our estimates of climate-relevant variables, particularly affecting the regional variability of the single-scattering albedo at solar wavelengths or the total iron deposited over oceans. All in all, this assessment represents a baseline for future model experiments including new mineralogical maps constrained by high-quality spaceborne hyperspectral measurements, such as those arising from the NASA Earth Surface Mineral Dust Source Investigation (EMIT) mission.</p

High cocoa polyphenol rich chocolate may reduce the burden of the symptoms in chronic fatigue syndrome

<p>Abstract</p> <p>Background</p> <p>Chocolate is rich in flavonoids that have been shown to be of benefit in disparate conditions including cardiovascular disease and cancer. The effect of polyphenol rich chocolate in subjects with chronic fatigue syndrome (CFS) has not been studied previously.</p> <p>Methods</p> <p>We conducted a double blinded, randomised, clinical pilot crossover study comparing high cocoa liquor/polyphenol rich chocolate (HCL/PR) in comparison to simulated iso-calorific chocolate (cocoa liquor free/low polyphenols(CLF/LP)) on fatigue and residual function in subjects with chronic fatigue syndrome. Subjects with CFS having severe fatigue of at least 10 out of 11 on the Chalder Fatigue Scale were enrolled. Subjects had either 8 weeks of intervention in the form of HCL/PR or CLF/LP, with a 2 week wash out period followed by 8 weeks of intervention with the other chocolate.</p> <p>Results</p> <p>Ten subjects were enrolled in the study. The Chalder Fatigue Scale score improved significantly after 8 weeks of the HCL/PR chocolate arm [median (range) Exact Sig. (2-tailed)] [33 (25 - 38) vs. 21.5 (6 - 35) 0.01], but that deteriorated significantly when subjects were given simulated iso-calorific chocolate (CLF/CP) [ 28.5 (17 - 20) vs. 34.5 (13-26) 0.03]. The residual function, as assessed by the London Handicap scale, also improved significantly after the HCL/PR arm [0.49 (0.33 - 0.62) vs. 0.64 (0.44 - 0.83) 0.01] and deteriorated after iso-calorific chocolate [00.44 (0.43 - 0.68) vs. 0.36 (0.33 - 0.62)0.03]. Likewise the Hospital Anxiety and Depression score also improved after the HCL/PR arm, but deteriorated after CLF/CP. Mean weight remained unchanged throughout the trial.</p> <p>Conclusion</p> <p>This study suggests that HCL/PR chocolate may improve symptoms in subjects with chronic fatigue syndrome.</p

The Dynamic X-ray Sky of the Local Universe

Over the next decade, we can expect time domain astronomy to flourish at optical and radio wavelengths. In parallel with these efforts, a dedicated transient "machine" operating at higher energies (X-ray band through soft gamma-rays) is required to reveal the unique subset of events with variable emission predominantly visible above 100 eV. Here we focus on the transient phase space never yet sampled due to the lack of a sensitive, wide-field and triggering facility dedicated exclusively to catching high energy transients and enabling rapid coordinated multi-wavelength follow-up. We first describe the advancements in our understanding of known X-ray transients that can only be enabled through such a facility and then focus on the classes of transients theoretically predicted to be out of reach of current detection capabilities. Finally there is the exciting opportunity of revealing new classes of X-ray transients and unveiling their nature through coordinated follow-up observations at longer wavelengths.Comment: 8 pages, 2 figures; White Paper submitted to the Astro2010 SSE pane