Very High Energy Gamma-ray spectral properties of Mrk 501 from CAT Cerenkov telescope observations in 1997

The BL Lac object Mrk 501 went into a very high state of activity during 1997, both in VHE gamma-rays and X-rays. We present here results from observations at energies above 250 GeV carried out between March and October 1997 with the CAT Cerenkov imaging Telescope. The average differential spectrum between 30 GeV and 13 TeV shows significant curvature and is well represented by phi_0 * E_TeV^{-(alpha + beta*log10(E_TeV))}, with: phi_0 = 5.19 +/- 0.13 {stat} +/- 0.12 {sys-MC} +1.66/-1.04 {sys-atm} * 10^-11 /cm^2/s/TeV alpha = 2.24 +/- 0.04 {stat} +/- 0.05 {sys} beta = 0.50 +/- 0.07 {stat} (negligible systematics). The TeV spectral energy distribution of Mrk 501 clearly peaks in the range 500 GeV-1 TeV. Investigation of spectral variations shows a significant hardness-intensity correlation with no measurable effect on the curvature. This can be described as an increase of the peak TeV emission energy with intensity. Simultaneous and quasi-simultaneous CAT VHE gamma-ray and BeppoSAX hard X-ray detections for the highest recorded flare on 16th April and for lower-activity states of the same period show correlated variability with a higher luminosity in X-rays than in gamma-rays. The observed spectral energy distribution and the correlated variability between X-rays and gamma-rays, both in amplitude and in hardening of spectra, favour a two-component emission scheme where the low and high energy components are attributed to synchrotron and inverse Compton (IC) radiation, respectively.Comment: Submitted to Astronomy and Astrophysics, 8 pages including 6 figures. Published with minor change

Spectrum and Variability of Mrk501 as observed by the CAT Imaging Telescope

The CAT Imaging Telescope has observed the BL Lac object Markarian 501 between March and August 1997. We report here on the variability over this time including several large flares. We present also preliminary spectra for all these data, for the low emission state, and for the largest flare.Comment: 4 pages, 4 figures, Late

The CAT Imaging Telescope for Very-High-Energy Gamma-Ray Astronomy

The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a very-high-definition camera (546 fast phototubes with 0.12 degrees spacing surrounded by 54 larger tubes in two guard rings) started operation in Autumn 1996 on the site of the former solar plant Themis (France). Using the atmospheric Cherenkov technique, it detects and identifies very high energy gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in detail.Comment: 24 pages, 15 figures. submitted to Elsevier Preprin

Detection of the BL Lac object 1ES1426+428 in the Very High Energy gamma-ray band by the CAT Telescope from 1998-2000

The BL Lac Object 1ES 1426+428, at a red-shift of z=0.129, has been monitored by the CAT telescope from February 1998 to June 2000. The accumulation of 26 hours of observations shows a gamma-ray signal of 321 events above 250 GeV at 5.2 standard deviations, determined using data analysis cuts adapted to a weak, steep-spectrum source. The source emission has an average flux of Phi_diff(400 GeV) = 6.73 +/- 1.27stat +/- 1.45syst x 10^-11 /cm^-2/s/TeV, and a very steep spectrum, with a differential spectral index of gamma = -3.60 +/- 0.57 which can be refined to gamma = -3.66 +/- 0.41 using a higher flux data subset. If, as expected from its broad-band properties, the Very High Energy emission is hard at the source, these observations support a strong absorption effect of gamma-rays by the Intergalactic Infrared field.Comment: 4 pages, 3 figures, accepted for publication in A&A Letter

Activation of FGF Signaling Mediates Proliferative and Osteogenic Differences between Neural Crest Derived Frontal and Mesoderm Parietal Derived Bone

BACKGROUND: As a culmination of efforts over the last years, our knowledge of the embryonic origins of the mammalian frontal and parietal cranial bones is unambiguous. Progenitor cells that subsequently give rise to frontal bone are of neural crest origin, while parietal bone progenitors arise from paraxial mesoderm. Given the unique qualities of neural crest cells and the clear delineation of the embryonic origins of the calvarial bones, we sought to determine whether mouse neural crest derived frontal bone differs in biology from mesoderm derived parietal bone. METHODS: BrdU incorporation, immunoblotting and osteogenic differentiation assays were performed to investigate the proliferative rate and osteogenic potential of embryonic and postnatal osteoblasts derived from mouse frontal and parietal bones. Co-culture experiments and treatment with conditioned medium harvested from both types of osteoblasts were performed to investigate potential interactions between the two different tissue origin osteoblasts. Immunoblotting techniques were used to investigate the endogenous level of FGF-2 and the activation of three major FGF signaling pathways. Knockdown of FGF Receptor 1 (FgfR1) was employed to inactivate the FGF signaling. RESULTS: Our results demonstrated that striking differences in cell proliferation and osteogenic differentiation between the frontal and parietal bone can be detected already at embryonic stages. The greater proliferation rate, as well as osteogenic capacity of frontal bone derived osteoblasts, were paralleled by an elevated level of FGF-2 protein synthesis. Moreover, an enhanced activation of FGF-signaling pathways was observed in frontal bone derived osteoblasts. Finally, the greater osteogenic potential of frontal derived osteoblasts was dramatically impaired by knocking down FgfR1. CONCLUSIONS: Osteoblasts from mouse neural crest derived frontal bone displayed a greater proliferative and osteogenic potential and endogenous enhanced activation of FGF signaling compared to osteoblasts from mesoderm derived parietal bone. FGF signaling plays a key role in determining biological differences between the two types of osteoblasts

Regulation of vascular smooth muscle cell calcification by syndecan-4/FGF-2/PKCα signaling and cross-talk with TGFβ

Aims: Vascular calcification is a major cause of morbidity and mortality. Fibroblast growth factor-2 (FGF-2) plays an instructive role in osteogenesis and bone development, but its role in vascular calcification was unknown. Therefore, we investigated the involvement of FGF-2 in vascular calcification and determined the mechanism by which it regulates this process. Methods and Results: We demonstrate that FGF-2 expression is increased in vascular smooth muscle cells (VSMCs) induced to deposit a mineralized matrix by incubation with β-glycerophosphate. FGF-2 is also localized to sites of calcification within human atherosclerotic plaques. The expression of syndecan-4, a heparan sulfate proteoglycan which regulates FGF-2 signaling, is also increased in mineralizing VSMCs and co-localizes with FGF-2 in human calcified atherosclerotic plaques. Exogenous FGF-2 inhibits VSMC mineralization, and this inhibition is reduced when syndecan-4 expression is knocked-down using siRNA. Biochemical inhibition of FGFR signaling using a pan FGFR inhibitor (BGJ398) or knocking-down syndecan-4 expression in VSMCs using siRNA increases VSMC mineralization. These increases are prevented by inhibiting transforming growth factor-β (TGFβ) signaling with SB431542, suggesting cross-talk between FGF-2 and TGFβ signaling is crucial for the regulation of VSMC mineralization. Syndecan-4 can also regulate FGF-2 signaling directly via protein kinase Cα (PKCα) activation. Biochemical inhibition of PKCα activity using Gö6976, or siRNA-mediated suppression of PKCα expression increases VSMC mineralization; this increase is also prevented with SB431542. Finally, the ability of FGF-2 to inhibit VSMC mineralization is reduced when PKCα expression is knocked-down. Conclusion: This is the first demonstration that syndecan-4 promotes FGF-2 signaling, and in turn, suppresses VSMC mineralization by down-regulating TGFβ signaling. Our discoveries that FGF-2 and syndecan-4 expression is increased in mineralizing VSMCs and that PKCα regulates FGF-2 and TGFβ signaling in VSMCs suggests that the syndecan-4/FGF-2/TGFβ signaling axis could represent a new therapeutic target for vascular calcification

The CAT Imaging Telescope

The VHE gamma-ray imaging telescope CAT started taking data in October 1996. Located at the Themis solar site in southern France, it features a 17.7 m^2 Davies-Cotton mirror equipped with 600 PMT camera at the focal plane. The mechanics and optics, the PMTs and the electronics are presented. The performance, based on the first 7 months of operation, is described

Temporal and spectral gamma-ray properties of Mkn421 above 250 GeV from CAT observations between 1996 and 2000

The gamma-ray emission above 250 GeV from the BL Lac object Markarian 421 was observed by the CAT Cherenkov imaging telescope between December, 1996, and June, 2000. In 1998, the source produced a series of small flares, making it the second extragalactic source detected by CAT. The time-averaged differential spectrum has been measured from 0.3 to 5 TeV, which is well fitted with a power law with an index of -2.88+-0.12(stat)+-0.06(syst). In 2000, the source showed an unprecedented activity, with variability time-scales as short as one hour, as for instance observed during the night between 4 and 5 February. The 2000 time-averaged spectrum measured is compatible with that of 1998, but some indication of a spectral curvature is found between 0.3 and 5 TeV. The possibility of TeV spectral hardening during flares is also discussed, and the results are compared to those obtained on the other TeV BL Lac, Markarian 501.Comment: Latex2e, 11 pages, 7 figures, accepted for publication in Astronomy & Astrophysic

Prototype Tests for the CELESTE Solar Array Gamma--Ray Telescope

The CELESTE experiment will be an Atmospheric Cherenkov detector designed to bridge the gap in energy sensitivity between current satellite and ground-based gamma-ray telescopes, 20 to 300 GeV. We present test results made at the former solar power plant, Themis, in the French Pyrenees. The tests confirm the viability of using a central tower heliostat array for Cherenkov wavefront sampling.Comment: LaTeX2e,30 pages including 14 figures, accepted for publication by Nuclear Instruments & Methods Section

Compliance and treatment satisfaction of post menopausal women treated for osteoporosis. Compliance with osteoporosis treatment

International audienceBackgroundAdherence to anti-osteoporosis treatments is poor, exposing treated women to increased fracture risk. Determinants of poor adherence are poorly understood. The study aims to determine physician- and patient- rated treatment compliance with osteoporosis treatments and to evaluate factors influencing compliance.MethodsThis was an observational, cross-sectional pharmacoepidemiological study with a randomly-selected sample of 420 GPs, 154 rheumatologists and 110 gynaecologists practicing in France. Investigators included post-menopausal women with a diagnosis of osteoporosis and a treatment initiated in the previous six months. Investigators completed a questionnaire on clinical features, treatments and medical history, and on patient compliance. Patients completed a questionnaire on sociodemographic features, lifestyle, attitudes and knowledge about osteoporosis, treatment compliance, treatment satisfaction and quality of life. Treatment compliance was evaluated with the Morisky Medication-taking Adherence Scale. Variables collected in the questionnaires were evaluated for association with compliance using multivariate logistic regression analysis.Results785 women were evaluated. Physicians considered 95.4% of the sample to be compliant, but only 65.5% of women considered themselves compliant. The correlation between patient and physician perceptions of compliance was low (κ: 0.11 [95% CI: 0.06 to 0.16]). Patient-rated compliance was highest for monthly bisphosphonates (79.7%) and lowest for hormone substitution therapy (50.0%). Six variables were associated with compliance: treatment administration frequency, perceptions of long-term treatment acceptability, perceptions of health consequences of osteoporosis, perceptions of knowledge about osteoporosis, exercise and mental quality of life.ConclusionCompliance to anti-osteoporosis treatments is poor. Reduction of dosing regimen frequency and patient education may be useful ways of improving compliance