Genetic issues in the diagnosis of dystonias

Dystonias are heterogeneous hyperkinetic movement disorders characterized by involuntary muscle contractions which result in twisting and repetitive movements and abnormal postures. Several causative genes have been identified, but their genetic bases still remain elusive. Primary Torsion Dystonias (PTDs), in which dystonia is the only clinical sign, can be inherited in a monogenic fashion, and many genes and loci have been identified for autosomal dominant (DYT1/TOR1A; DYT6/THAP1; DYT4/TUBB4a; DYT7; DYT13; DYT21; DYT23/CIZ1; DYT24/ANO3; DYT25/GNAL) and recessive (DYT2; DYT17) forms. However most sporadic cases, especially those with late-onset, are likely multifactorial, with genetic and environmental factors interplaying to reach a threshold of disease. At present, genetic counseling of dystonia patients remains a difficult task. Recently non-motor clinical findings in dystonias, new highlights in the pathophysiology of the disease, and the availability of high-throughput genome-wide techniques are proving useful tools to better understand the complexity of PTD genetics. We briefly review the genetic basis of the most common forms of hereditary PTDs, and discuss relevant issues related to molecular diagnosis and genetic counseling

Absorption lines from magnetically-driven winds in X-ray binaries

High resolution X-ray spectra of black hole X-ray binaries (BHBs) show blueshifted absorption lines from disk winds which seem to be equatorial. Winds occur in the Softer (disk-dominated) states of the outburst and are less prominent or absent in the Harder (power-law dominated) states. We use self-similar magneto-hydrodynamic (MHD) accretion-ejection models to explain the disk winds in BHBs. In our models, the density at the base of the outflow from the accretion disk is not a free parameter, but is determined by solving the full set of dynamical MHD equations. Thus the physical properties of the outflow are controlled by the global structure of the disk. We studied different MHD solutions characterized by different values of (a) the disk aspect ratio ($\varepsilon$) and (b) the ejection efficiency ($p$). We use two kinds of MHD solutions depending on the absence (cold solution) or presence (warm solution) of heating at the disk surface. Such heating could be from e.g. dissipation of energy due to MHD turbulence in the disk or from illumination. We use each of these MHD solutions to predict the physical parameters of an outflow; put limits on the ionization parameter ($\xi$), column density and timescales, motivated by observational results; and thus select regions within the outflow which are consistent with the observed winds. The cold MHD solutions cannot account for winds due to their low ejection efficiency. But warm solutions can explain the observed physical quantities in the wind because they can have sufficiently high values of $p$ ($\gtrsim 0.1$, implying larger mass loading at the base of the outflow). Further from our thermodynamic equilibrium curve analysis for the outflowing gas, we found that in the Hard state a range of $\xi$ is thermodynamically unstable, and had to be excluded. This constrain made it impossible to have any wind at all, in the Hard state.Comment: 16 Pages, 10 figures in the main body and 4 figures in the appendix. Accepted for publication in A&

Effect of insulin glargine on cardiovascular risk analysed by mean HRV

Type 2 diabetes mellitus is an insidious disease that is increasingly present in geriatric population [1]. The greatest difficulty is represented by glycaemic control in geriatric patients often not very compliant with diet therapy and drug therapy. A new insulin glargine 300 units/ml formulation seems im- prove patient compliance due to the lower volume of insulin to be injected and improved glycaemic control over 24 hours. The HRV signal, derived from digital electrocardiographic recording, is the simplest and most imme- diate analysis that consists in calculating some temporal parameters [2]. HRV is a simple statistics derived from beat-beat intervals of sinus origin expressed as units of time in milliseconds. Data in the literature indicate that a decrease in HRV, measured with time domain analysis, denotes a worse prognosis and/or an increased risk of mortality in patients with heart disease, especially in the elderly ones

Multiwavelength campaign on Mrk 509 XV. A global modeling of the broad emission lines in the Optical, UV and X-ray bands

We model the broad emission lines present in the optical, UV and X-ray spectra of Mrk 509, a bright type 1 Seyfert galaxy. The broad lines were simultaneously observed during a large multiwavelength campaign, using the XMM-Newton-OM for the optical lines, HST-COS for the UV lines and XMM-Newton-RGS and Epic for the X-ray lines respectively. We also used FUSE archival data for the broad lines observed in the far-ultra-violet. The goal is to find a physical connection among the lines measured at different wavelengths and determine the size and the distance from the central source of the emitting gas components. We used the "Locally optimally emission Cloud" (LOC) model which interprets the emissivity of the broad line region (BLR) as regulated by powerlaw distributions of both gas density and distances from the central source. We find that one LOC component cannot model all the lines simultaneously. In particular, we find that the X-ray and UV lines likely may originate in the more internal part of the AGN, at radii in the range ~5x10^{14}-3x10^{17} cm, while the optical lines and part of the UV lines may likely be originating further out, at radii ~3x10^{17}-3x^{18} cm. These two gas components are parametrized by a radial distribution of the luminosities with a slope gamma of ~1.15 and ~1.10, respectively, both of them covering at least 60% of the source. This simple parameterization points to a structured broad line region, with the higher ionized emission coming from closer in, while the emission of the low-ionization lines is more concentrated in the outskirts of the broad line region.Comment: 10 pages, 5 figures, accepted for publication in Astronomy and Astrophysic

Design of light concentrators for Cherenkov telescope observatories

The Cherenkov Telescope Array (CTA) will be the largest cosmic gamma ray detector ever built in the world. It will be installed at two different sites in the North and South hemispheres and should be operational for about 30 years. In order to cover the desired energy range, the CTA is composed of typically 50-100 collecting telescopes of various sizes (from 6 to 24-m diameters). Most of them are equipped with a focal plane camera consisting of 1500 to 2000 Photomultipliers (PM) equipped with light concentrating optics, whose double function is to maximize the amount of Cherenkov light detected by the photo-sensors, and to block any stray light originating from the terrestrial environment. Two different optical solutions have been designed, respectively based on a Compound Parabolic Concentrator (CPC), and on a purely dioptric concentrating lens. In this communication are described the technical specifications, optical designs and performance of the different solutions envisioned for all these light concentrators. The current status of their prototyping activities is also given

Multiwavelength campaign on Mrk 509 XII. Broad band spectral analysis

(Abridged) The simultaneous UV to X-rays/gamma rays data obtained during the multi-wavelength XMM/INTEGRAL campaign on the Seyfert 1 Mrk 509 are used in this paper and tested against physically motivated broad band models. Each observation has been fitted with a realistic thermal comptonisation model for the continuum emission. Prompted by the correlation between the UV and soft X-ray flux, we use a thermal comptonisation component for the soft X-ray excess. The UV to X-rays/gamma-rays emission of Mrk 509 can be well fitted by these components. The presence of a relatively hard high-energy spectrum points to the existence of a hot (kT~100 keV), optically-thin (tau~0.5) corona producing the primary continuum. On the contrary, the soft X-ray component requires a warm (kT~1 keV), optically-thick (tau~15) plasma. Estimates of the amplification ratio for this warm plasma support a configuration close to the "theoretical" configuration of a slab corona above a passive disk. An interesting consequence is the weak luminosity-dependence of its emission, a possible explanation of the roughly constant spectral shape of the soft X-ray excess seen in AGNs. The temperature (~ 3 eV) and flux of the soft-photon field entering and cooling the warm plasma suggests that it covers the accretion disk down to a transition radius $R_{tr}$ of 10-20 $R_g$. This plasma could be the warm upper layer of the accretion disk. On the contrary the hot corona has a more photon-starved geometry. The high temperature ($\sim$ 100 eV) of the soft-photon field entering and cooling it favors a localization of the hot corona in the inner flow. This soft-photon field could be part of the comptonised emission produced by the warm plasma. In this framework, the change in the geometry (i.e. $R_{tr}$) could explain most of the observed flux and spectral variability.Comment: 19 pages, 14 figures. Accepted for publication in A&

Multiwavelength campaign on Mrk 509. V. Chandra-LETGS observation of the ionized absorber

We present here the results of a 180 ks Chandra-LETGS observation as part of a large multi-wavelength campaign on Mrk 509. We study the warm absorber in Mrk 509 and use the data from a simultaneous HST-COS observation in order to assess whether the gas responsible for the UV and X-ray absorption are the same. We analyzed the LETGS X-ray spectrum of Mrk 509 using the SPEX fitting package. We detect several absorption features originating in the ionized absorber of the source, along with resolved emission lines and radiative recombination continua. The absorption features belong to ions with, at least, three distinct ionization degrees. The lowest ionized component is slightly redshifted (v = +73 km/s) and is not in pressure equilibrium with the others, and therefore it is not likely part of the outflow, possibly belonging to the interstellar medium of the host galaxy. The other components are outflowing at velocities of -196 and -455 km/s, respectively. The source was observed simultaneously with HST-COS, finding 13 UV kinematic components. At least three of them can be kinematically associated with the observed X-ray components. Based on the HST-COS results and a previous FUSE observation, we find evidence that the UV absorbing gas might be co-located with the X-ray absorbing gas and belong to the same structure.Comment: 12 pages, 7 figures, 9 tables. Accepted for publication in Astronomy & Astrophysic

The XMM/BeppoSAX observation of Mkn 841

Mkn 841 has been observed simultaneously by XMM and BeppoSAX in January 2001. Due to operational contingency, the 30ks XMM observation was split into two parts, separated by about 15 hours. We first report the presence of a narrow iron line which appears to be rapidly variable between the two pointings, requiring a non-standard interpretation. We then focus on the analysis of the broad band (0.3-200 keV) continuum using the XMM/EPIC, RGS and SAX/PDS data. The Mkn 841 spectrum is well fitted by a comptonization model in a geometry more photon-fed than a simple slab geometry above a passive disk. It presents a relatively large reflection (R>2) which does not agree with an apparently weak iron line. It also show the presence of a strong soft excess wellfitted by a comptonized spectrum in a cool plasma, suggesting the presence of a multi-temperature corona.Comment: 4 pages, 5 figures. Proc. of the meeting: "The Restless High-Energy Universe" (Amsterdam, The Netherlands), E.P.J. van den Heuvel, J.J.M. in 't Zand, and R.A.M.J. Wijers Ed

Multiwavelength campaign on Mrk 509. XIII. Testing ionized-reflection models on Mrk 509

Active Galactic Nuclei (AGN) are the most luminous persistent objects in the universe. An excess of X-ray emission below about 2 keV, called soft-excess, is very common in Type 1 AGN spectra. The origin of this feature remains debated. Originally modeled with a blackbody, there are now several possibilities to model the soft-excess, including warm Comptonization and blurred ionized reflection. In this paper, we test ionized-reflection models on Mrk 509, a bright Seyfert 1 galaxy for which we have a unique data set, in order to determine whether it can be responsible for the strong soft-excess. We use ten simultaneous XMM-Newton and INTEGRAL observations performed every four days. We present here the results of the spectral analysis, the evolution of the parameters and the variability properties of the X-ray emission. The application of blurred ionized-reflection models leads to a very strong reflection and an extreme geometry, but fails to reproduce the broad-band spectrum of Mrk 509. Two different scenarios for blurred ionized reflection are discussed: stable geometry and lamp-post configuration. In both cases we find that the model parameters do not follow the expected relations, indicating that the model is fine-tuned to fit the data without physical justification. A large, slow variation of the soft-excess without counterpart in the hard X-rays could be explained by a change in ionization of the reflector. However, such a change does not naturally follow from the assumed geometrical configuration. Warm Comptonization remains the most probable origin of the soft-excess in this object. Nevertheless, it is possible that both ionized reflection and warm Comptonization mechanisms can explain the soft-excess in all objects, one dominating the other one, depending on the physical conditions of the disk and the corona.Comment: 12 pages, A&A accepte

Study of MDT calibration constants using H8 testbeam data of year 2004

In year 2004 Atlas performed a long campaign of test beam data taking at the H8 Cern beam. Two sectors of the barrel and endcap regions of the Muon Spectrometer were exposed to the beam and large amount of data were collected in well defined and controlled operating conditions. This allowed a careful study on MDT drift properties. A better understanding of the calibration constants, of their definition and determination and of the criteria for their acceptance has been obtained. Systematic effects and time stability of the constants have also been studied