Allelic and phenotypic characterization of CYP2D6 and its encoded P450 cytochrome enzyme in a serie of Spanish type 1 Gaucher disease patients

Background: Cytochrome p450 is the main drug metabolic pathway. CYP2D6 is a highly polymorphic gene that encodes a cytochrome p450 enzyme with three activity levels: null, reduced and normal. Apart from another type of mutations CYP2D6 can suffer duplications and deletions of the entire gene. This is the pathway to metabolize one of the Gaucher disease treatments, whose dose administration is regulated according to the metabolizer phenotype, this being one of the administration limitations. Objectives: The aim of this paper is to evaluate the allelic frequencies and the metabolizer status of Gaucher type 1 patients in the Spanish population and compare it with the general Spanish population and other Gaucher disease groups. Methods: In this study, 109 type 1 Gaucher disease patients were analyzed with the xTAG®CYP2D6 kit to identify the CYP2D6 gene alleles. Results: We observed that eighty-seven patients could be classified as extensive, 14 as intermediate, 6 as poor and 2 as ultra-rapid metabolizers. The allelic duplication frequency is 5.5% and deletion is 4.5%. The most common allele is wild-type and the second is the null *4 allele. Intermediate phenotype frequency is higher than expected (p < 0.05). Conclusions: Our Spanish GD series shows an unexpected distribution of some alleles and phenotypic metabolizer status, in contrast to that previously reported in the Spanish population

Electron transport properties of sub-3-nm diameter copper nanowires

Density functional theory and density functional tight-binding are applied to model electron transport in copper nanowires of approximately 1 nm and 3 nm diameters with varying crystal orientation and surface termination. The copper nanowires studied are found to be metallic irrespective of diameter, crystal orientation and/or surface termination. Electron transmission is highly dependent on crystal orientation and surface termination. Nanowires oriented along the [110] crystallographic axis consistently exhibit the highest electron transmission while surface oxidized nanowires show significantly reduced electron transmission compared to unterminated nanowires. Transmission per unit area is calculated in each case, for a given crystal orientation we find that this value decreases with diameter for unterminated nanowires but is largely unaffected by diameter in surface oxidized nanowires for the size regime considered. Transmission pathway plots show that transmission is larger at the surface of unterminated nanowires than inside the nanowire and that transmission at the nanowire surface is significantly reduced by surface oxidation. Finally, we present a simple model which explains the transport per unit area dependence on diameter based on transmission pathways results

Enceladus: Biosignatures

Saturn's moon Enceladus is a new world for Astrobiology. Through the study of Enceladus' plumes new insights into its habitability will be gained. The four core parameters for life include: water, carbon, nitrogen, and energy; all were found in the plume. Carbon and nitrogen in the plume exist in forms easily usable by biological systems (CH4, HCN, NH3, H2, CO2, and organics up to C6). The first step to search for evidence of life is to define potential biosignatures for Enceladus

High-excitation OH and H_2O lines in Markarian 231: the molecular signatures of compact far-infrared continuum sources

The ISO/LWS far-infrared spectrum of the ultraluminous galaxy Mkn 231 shows OH and H_2O lines in absorption from energy levels up to 300 K above the ground state, and emission in the [O I] 63 micron and [C II] 158 micron lines. Our analysis shows that OH and H_2O are radiatively pumped by the far-infrared continuum emission of the galaxy. The absorptions in the high-excitation lines require high far-infrared radiation densities, allowing us to constrain the properties of the underlying continuum source. The bulk of the far-infrared continuum arises from a warm (T_dust=70-100 K), optically thick (tau_100micron=1-2) medium of effective diameter 200-400 pc. In our best-fit model of total luminosity L_IR, the observed OH and H2O high-lying lines arise from a luminous (L/L_IR~0.56) region with radius ~100 pc. The high surface brightness of this component suggests that its infrared emission is dominated by the AGN. The derived column densities N(OH)>~10^{17} cm^{-2} and N(H_2O)>~6x10^{16} cm^{-2} may indicate XDR chemistry, although significant starburst chemistry cannot be ruled out. The lower-lying OH, [C II] 158 micron, and [O I] 63 micron lines arise from a more extended (~350 pc) starburst region. We show that the [C II] deficit in Mkn 231 is compatible with a high average abundance of C+ because of an extreme overall luminosity to gas mass ratio. Therefore, a [C II] deficit may indicate a significant contribution to the luminosity by an AGN, and/or by extremely efficient star formation.Comment: 16 pages, 6 figures, accepted for publication in The Astrophysical Journa

The Non-thermal Radio Jet Toward the NGC 2264 Star Formation Region

We report sensitive VLA 3.6 cm radio observations toward the head of the Cone nebula in NGC 2264, made in 2006. The purpose of these observations was to study a non-thermal radio jet recently discovered, that appears to emanate from the head of the Cone nebula. The jet is highly polarized, with well-defined knots, and one-sided. The comparison of our images with 1995 archive data indicates no evidence of proper motions nor polarization changes. We find reliable flux density variations in only one knot, which we tentatively identify as the core of a quasar or radio galaxy. An extragalactic location seems to be the best explanation for this jet.Comment: 12 pages, 5 figure

The Second INTEGRAL AGN Catalogue

The INTEGRAL mission provides a large data set for studying the hard X-ray properties of AGN and allows testing of the unified scheme for AGN. We present analysis of INTEGRAL IBIS/ISGRI, JEM-X, and OMC data for 199 AGN supposedly detected by INTEGRAL above 20 keV. The data analysed here allow a significant spectral extraction on 148 objects and an optical variability study of 57 AGN. The slopes of the hard X-ray spectra of Seyfert 1 and Seyfert~2 galaxies are found to be consistent within the uncertainties, whereas higher cut-off energies and lower luminosities are measured for the more absorbed / type 2 AGN. The intermediate Seyfert 1.5 objects exhibit hard X-ray spectra consistent with those of Seyfert 1. When applying a Compton reflection model, the underlying continua appear the same in Seyfert 1 and 2 with photon index 2, and the reflection strength is about R = 1, when assuming different inclination angles. A significant correlation is found between the hard X-ray and optical luminosity and the mass of the central black hole in the sense that the more luminous objects appear to be more massive. There is also a general trend toward the absorbed sources and type 2 AGN having lower Eddington ratios. The black holemass appears to form a fundamental plane together with the optical and X-ray luminosity of the form Lv being proportional to Lx^0.6 M^0.2, similar to that found between radio luminosity Lr, Lx, and M. The unified model for Seyfert galaxies seems to hold, showing in hard X-rays that the central engine is the same in Seyfert 1 and 2, but seen under different inclination angles and absorption. (Abridged)Comment: 26 pages, 16 figures, accepted for publication in A&A. Corrections by language editor included in version

Filtered Noise Can Mimic Low-Dimensional Chaotic Attractors

This contribution presents four results. First, calculations indicate that when examined by the Grassberger-Procaccia algorithm alone, filtered noise can mimic low-dimensional chaotic attractors. Given the ubiquity Of signal filtering in experimental investigations, this is potentially important. Second, a criterion is derived which provides an estimate of the minimum data accuracy needed to resolve the dimension of an attractor. Third, it is shown that a criterion derived by Eckmann and Ruelle [Physica D 56, 185 (1992)] to estimate the minimum number of data points required in a Grassberger-Procaccia calculation can be used to provide a further check on these dimension estimates. Fourth, it is shown that surrogate data techniques recently published by Theiler and his colleagues [in Nonlinear Modeling and Forecasting, edited by M. Casdagli and S. Eubanks (Addison Wesley, Reading, MA, 1992)] can successfully distinguish between linearly correlated noise and nonlinear structure. These results, and most particularly the first, indicate that Grassberger-Procaccia results must be interpreted with far greater circumspection than has previously been the case, and that the algorithm should be used in combination with additional procedures such as calculations with surrogate data. When filtered signals are examined by this algorithm alone, a finite noninteger value of D2 is consistent with low-dimensional chaotic behavior, but it is certainly not a definitive diagnostic of chaos

Constraints on the H2O formation mechanism in the wind of carbon-rich AGB stars

Context. The recent detection of warm H$_2$O vapor emission from the outflows of carbon-rich asymptotic giant branch (AGB) stars challenges the current understanding of circumstellar chemistry. Two mechanisms have been invoked to explain warm H$_2$O vapor formation. In the first, periodic shocks passing through the medium immediately above the stellar surface lead to H$_2$O formation. In the second, penetration of ultraviolet interstellar radiation through a clumpy circumstellar medium leads to the formation of H$_2$O molecules in the intermediate wind. Aims. We aim to determine the properties of H$_2$O emission for a sample of 18 carbon-rich AGB stars and subsequently constrain which of the above mechanisms provides the most likely warm H$_2$O formation pathway. Methods, Results, and Conclusions. See paper