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

Hypoxia Potentiates Glioma-Mediated Immunosuppression

Glioblastoma multiforme (GBM) is a lethal cancer that exerts potent immune suppression. Hypoxia is a predominant feature of GBM, but it is unclear to the degree in which tumor hypoxia contributes to this tumor-mediated immunosuppression. Utilizing GBM associated cancer stem cells (gCSCs) as a treatment resistant population that has been shown to inhibit both innate and adaptive immune responses, we compared immunosuppressive properties under both normoxic and hypoxic conditions. Functional immunosuppression was characterized based on production of immunosuppressive cytokines and chemokines, the inhibition of T cell proliferation and effector responses, induction of FoxP3+ regulatory T cells, effect on macrophage phagocytosis, and skewing to the immunosuppressive M2 phenotype. We found that hypoxia potentiated the gCSC-mediated inhibition of T cell proliferation and activation and especially the induction of FoxP3+T cells, and further inhibited macrophage phagocytosis compared to normoxia condition. These immunosuppressive hypoxic effects were mediated by signal transducer and activator of transcription 3 (STAT3) and its transcriptionally regulated products such as hypoxia inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF). Inhibitors of STAT3 and HIF-1α down modulated the gCSCs' hypoxia-induced immunosuppressive effects. Thus, hypoxia further enhances GBM-mediated immunosuppression, which can be reversed with therapeutic inhibition of STAT3 and HIF-1α and also helps to reconcile the disparate findings that immune therapeutic approaches can be used successfully in model systems but have yet to achieve generalized successful responses in the vast majority of GBM patients by demonstrating the importance of the tumor hypoxic environment

Anti-angiogenic therapy for cancer: Current progress, unresolved questions and future directions

Tumours require a vascular supply to grow and can achieve this via the expression of pro-angiogenic growth factors, including members of the vascular endothelial growth factor (VEGF) family of ligands. Since one or more of the VEGF ligand family is overexpressed in most solid cancers, there was great optimism that inhibition of the VEGF pathway would represent an effective anti-angiogenic therapy for most tumour types. Encouragingly, VEGF pathway targeted drugs such as bevacizumab, sunitinib and aflibercept have shown activity in certain settings. However, inhibition of VEGF signalling is not effective in all cancers, prompting the need to further understand how the vasculature can be effectively targeted in tumours. Here we present a succinct review of the progress with VEGF-targeted therapy and the unresolved questions that exist in the field: including its use in different disease stages (metastatic, adjuvant, neoadjuvant), interactions with chemotherapy, duration and scheduling of therapy, potential predictive biomarkers and proposed mechanisms of resistance, including paradoxical effects such as enhanced tumour aggressiveness. In terms of future directions, we discuss the need to delineate further the complexities of tumour vascularisation if we are to develop more effective and personalised anti-angiogenic therapies. © 2014 The Author(s)

The Large Observatory For X-ray Timing: LOFT

LOFT, the Large Observatory for X-ray Timing, is a new space mission concept devoted to observations of Galactic and extra-Galactic sources in the X-ray domain with the main goals of probing gravity theory in the very strong field environment of black holes and other compact objects, and investigating the state of matter at supra-nuclear densities in neutron stars. The instruments on-board LOFT, the Large area detector and the Wide Field Monitor combine for the first time an unprecedented large effective area (~10 m2 at 8 keV) sensitive to X-ray photons mainly in the 2-30 keV energy range and a spectral resolution approaching that of CCD-based telescopes (down to 200 eV at 6 keV). LOFT is currently competing for a launch of opportunity in 2022 together with the other M3 mission candidates of the ESA Cosmic Vision Progra

Anti-Vascular Endothelial Growth Factor Therapies as a Novel Therapeutic Approach to Treating Neurofibromatosis-Related Tumors

Patients with bilateral vestibular schwannomas associated with neurofibromatosis type 2 (NF2) experience significant morbidity such as complete hearing loss. We have recently shown that treatment with bevacizumab provided tumor stabilization and hearing recovery in a subset of NF2 patients with progressive disease. In the current study, we used two animal models to identify the mechanism of action of anti–vascular endothelial growth factor (VEGF) therapy in schwannomas. The human HEI193 and murine Nf2−/− cell lines were implanted between the pia and arachnoid meninges as well as in the sciatic nerve to mimic central and peripheral schwannomas. Mice were treated with bevacizumab (10 mg/kg/wk i.v.) or vandetanib (50 mg/kg/d orally) to block the VEGF pathway. Using intravital and confocal microscopy, together with whole-body imaging, we measured tumor growth delay, survival rate, as well as blood vessel structure and function at regular intervals. In both models, tumor vessel diameter, length/surface area density, and permeability were significantly reduced after treatment. After 2 weeks of treatment, necrosis in HEI193 tumors and apoptosis in Nf2−/− tumors were significantly increased, and the tumor growth rate decreased by an average of 50%. The survival of mice bearing intracranial schwannomas was extended by at least 50%. This study shows that anti-VEGF therapy normalizes the vasculature of schwannoma xenografts in nude mice and successfully controls the tumor growth, probably by reestablishing a natural balance between VEGF and semaphorin 3 signaling

CONCERTO en Ré majeur, Op. 7 N °6 (version Paumgartner) ; SONATE en La majeur, Op. 2 N °3 (version Giazotto) / Tommaso ALBINONI. CONCERTINO en Sol majeur / Giovanni PERGOLESE. CONCERTO en Ut majeur / Antonio VIVALDI ; les Virtuosi di Roma - Collegium Musicum Italicum - solistes : Renato Zanfini et Michele Visai, hautbois, dir. Renato Fasano

Titre uniforme : [Concertos. Hautbois (2), orchestre à cordes, basse continue. RV 534. Do majeur]Titre uniforme : [Concertino no 2 en sol majeur]Titre uniforme : [Concertos. Hautbois, orchestre à cordes, basse continue. G 72. Ré majeur]BnF-Partenariats, Collection sonore - BelieveContient une table des matière