Heritability of testosterone levels in 12-year-old twins and its relation to pubertal development

The aim of this study was to estimate the heritability of variation in testosterone levels in 12-year-old children, and to explore the overlap in genetic and environmental influences on circulating testosterone levels and androgen dependent pubertal development. Midday salivary testosterone samples were collected on two consecutive days in a sample of 183 unselected twin pairs. Androgen induced pubertal development was assessed using self report Tanner scales of pubic hair development (boys and girls) and genital development (boys). A significant contribution of genetic effects to the variance in testosterone levels was found. Heritability was approximately 50% in both boys and girls. The remaining proportion of the variance in testosterone levels could be explained by non-shared environmental influences. The relatively high correlation between testosterone levels of opposite sex dizygotic twins suggests that sex differences in genes influencing variation in testosterone levels have not yet developed in pre- and early puberty. Variance in pubertal development was explained by a large genetic component, moderate shared environmental influences, and a small non-shared environmental effect. Testosterone levels correlated moderately (r = .31) with pubertal development; the covariance between testosterone levels and pubertal development was entirely accounted for by genetic influences

A Spitzer Space Telescope study of SN 2002hh: an infrared echo from a Type IIP supernova

We present late-time (590-994 d) mid-IR photometry of the normal, but highly-reddened Type IIP supernova SN 2002hh. Bright, cool, slowly-fading emission is detected from the direction of the supernova. Most of this flux appears not to be driven by the supernova event but instead probably originates in a cool, obscured star-formation region or molecular cloud along the line-of-sight. We also show, however, that the declining component of the flux is consistent with an SN-powered IR echo from a dusty progenitor CSM. Mid-IR emission could also be coming from newly-condensed dust and/or an ejecta/CSM impact but their contributions are likely to be small. For the case of a CSM-IR echo, we infer a dust mass of as little as 0.036 M(solar) with a corresponding CSM mass of 3.6(0.01/r(dg))M(solar) where r(dg) is the dust-to-gas mass ratio. Such a CSM would have resulted from episodic mass loss whose rate declined significantly about 28,000 years ago. Alternatively, an IR echo from a surrounding, dense, dusty molecular cloud might also have been responsible for the fading component. Either way, this is the first time that an IR echo has been clearly identified in a Type IIP supernova. We find no evidence for or against the proposal that Type IIP supernovae produce large amounts of dust via grain condensation in the ejecta. However, within the CSM-IR echo scenario, the mass of dust derived implies that the progenitors of the most common of core-collapse supernovae may make an important contribution to the universal dust content.Comment: 41 pages, 11 figures, 4 tables, accepted for publication in Astrophysical Journal (References corrected

A Spitzer Space Telescope Study of SN 2003gd: Still No Direct Evidence that Core-Collapse Supernovae are Major Dust Factories

We present a new, detailed analysis of late-time mid-infrared (IR) observations of the Type II-P supernova (SN) 2003gd. At about 16 months after the explosion, the mid-IR flux is consistent with emission from 4 x 10^(-5) M(solar) of newly condensed dust in the ejecta. At 22 months emission from point-like sources close to the SN position was detected at 8 microns and 24 microns. By 42 months the 24 micron flux had faded. Considerations of luminosity and source size rule out the ejecta of SN 2003gd as the main origin of the emission at 22 months. A possible alternative explanation for the emission at this later epoch is an IR echo from pre-existing circumstellar or interstellar dust. We conclude that, contrary to the claim of Sugerman et al. (2006, Science, 313, 196), the mid-IR emission from SN 2003gd does not support the presence of 0.02 M(solar) of newly formed dust in the ejecta. There is, as yet, no direct evidence that core-collapse supernovae are major dust factories.Comment: 26 pages, 2 figures, 2 tables, accepted for publication in Astrophysical Journa

Integrating Systems around the User: Combining Isabelle, Maple, and QEPCAD in the Prover's Palette

AbstractWe describe the Proverʼs Palette, a general, modular architecture for combining tools for formal verification, with the key differentiator that the integration emphasises the role of the user. A concrete implementation combining the theorem prover Isabelle with the computer algebra systems Maple and QEPCAD-B is then presented. This illustrates that the design principles of the Proverʼs Palette simplify tool integrations while enhancing the power and usability of theorem provers

Exosomes containing HIV protein Nef reorganize lipid rafts potentiating inflammatory response in bystander cells.

HIV infection has a profound effect on "bystander" cells causing metabolic co-morbidities. This may be mediated by exosomes secreted by HIV-infected cells and containing viral factors. Here we show that exosomes containing HIV-1 protein Nef (exNef) are rapidly taken up by macrophages releasing Nef into the cell interior. This caused down-regulation of ABCA1, reduction of cholesterol efflux and sharp elevation of the abundance of lipid rafts through reduced activation of small GTPase Cdc42 and decreased actin polymerization. Changes in rafts led to re-localization of TLR4 and TREM-1 to rafts, phosphorylation of ERK1/2, activation of NLRP3 inflammasome, and increased secretion of pro-inflammatory cytokines. The effects of exNef on lipid rafts and on inflammation were reversed by overexpression of a constitutively active mutant of Cdc42. Similar effects were observed in macrophages treated with exosomes produced by HIV-infected cells or isolated from plasma of HIV-infected subjects, but not with exosomes from cells and subjects infected with ΔNef-HIV or uninfected subjects. Mice injected with exNef exhibited monocytosis, reduced ABCA1 in macrophages, increased raft abundance in monocytes and augmented inflammation. Thus, Nef-containing exosomes potentiated pro-inflammatory response by inducing changes in cholesterol metabolism and reorganizing lipid rafts. These mechanisms may contribute to HIV-associated metabolic co-morbidities

Analysis of the Flux and Polarization Spectra of the Type Ia Supernova SN 2001el: Exploring the Geometry of the High-velocity Ejecta

SN 2001el is the first normal Type Ia supernova to show a strong, intrinsic polarization signal. In addition, during the epochs prior to maximum light, the CaII IR triplet absorption is seen distinctly and separately at both normal photospheric velocities and at very high velocities. The high-velocity triplet absorption is highly polarized, with a different polarization angle than the rest of the spectrum. The unique observation allows us to construct a relatively detailed picture of the layered geometrical structure of the supernova ejecta: in our interpretation, the ejecta layers near the photosphere (v \approx 10,000 km/s) obey a near axial symmetry, while a detached, high-velocity structure (v \approx 18,000-25,000 km/s) with high CaII line opacity deviates from the photospheric axisymmetry. By partially obscuring the underlying photosphere, the high-velocity structure causes a more incomplete cancellation of the polarization of the photospheric light, and so gives rise to the polarization peak and rotated polarization angle of the high-velocity IR triplet feature. In an effort to constrain the ejecta geometry, we develop a technique for calculating 3-D synthetic polarization spectra and use it to generate polarization profiles for several parameterized configurations. In particular, we examine the case where the inner ejecta layers are ellipsoidal and the outer, high-velocity structure is one of four possibilities: a spherical shell, an ellipsoidal shell, a clumped shell, or a toroid. The synthetic spectra rule out the spherical shell model, disfavor a toroid, and find a best fit with the clumped shell. We show further that different geometries can be more clearly discriminated if observations are obtained from several different lines of sight.Comment: 14 pages (emulateapj5) plus 18 figures, accepted by The Astrophysical Journa

Near-infrared observations of type Ia supernovae: The best known standard candle for cosmology

We present an analysis of the Hubble diagram for 12 Type Ia supernovae (SNe Ia) observed in the near-infrared J and H bands. We select SNe exclusively from the redshift range 0.03 < z < 0.09 to reduce uncertainties coming from peculiar velocities while remaining in a cosmologically well-understood region. All of the SNe in our sample exhibit no spectral or B-band light-curve peculiarities and lie in the B-band stretch range of 0.8-1.15. Our results suggest that SNe Ia observed in the near-infrared (NIR) are the best known standard candles. We fit previously determined NIR light-curve templates to new high-precision data to derive peak magnitudes and to determine the scatter about the Hubble line. Photometry of the 12 SNe is presented in the natural system. Using a standard cosmology of (H_0, Omega_m, Lambda) = (70,0.27,0.73) we find a median J-band absolute magnitude of M_J = -18.39 with a scatter of 0.116 and a median H-band absolute magnitude of M_H = -18.36 with a scatter of 0.085. The scatter in the H band is the smallest yet measured. We search for correlations between residuals in the J- and H-band Hubble diagrams and SN properties, such as SN colour, B-band stretch and the projected distance from host-galaxy centre. The only significant correlation is between the J-band Hubble residual and the J-H pseudo-colour. We also examine how the scatter changes when fewer points in the near-infrared are used to constrain the light curve. With a single point in the H band taken anywhere from 10 days before to 15 days after B-band maximum light and a prior on the date of H-band maximum set from the date of B-band maximum, we find that we can measure distances to an accuracy of 6%. The precision of SNe Ia in the NIR provides new opportunities for precision measurements of both the expansion history of the universe and peculiar velocities of nearby galaxies.Comment: 6 pages, 2 figures. Accepted for publication in MNRA

Time Dependent Monte Carlo Radiative Transfer Calculations For 3-Dimensional Supernova Spectra, Lightcurves, and Polarization

We discuss Monte-Carlo techniques for addressing the 3-dimensional time-dependent radiative transfer problem in rapidly expanding supernova atmospheres. The transfer code SEDONA has been developed to calculate the lightcurves, spectra, and polarization of aspherical supernova models. From the onset of free-expansion in the supernova ejecta, SEDONA solves the radiative transfer problem self-consistently, including a detailed treatment of gamma-ray transfer from radioactive decay and with a radiative equilibrium solution of the temperature structure. Line fluorescence processes can also be treated directly. No free parameters need be adjusted in the radiative transfer calculation, providing a direct link between multi-dimensional hydrodynamical explosion models and observations. We describe the computational techniques applied in SEDONA, and verify the code by comparison to existing calculations. We find that convergence of the Monte Carlo method is rapid and stable even for complicated multi-dimensional configurations. We also investigate the accuracy of a few commonly applied approximations in supernova transfer, namely the stationarity approximation and the two-level atom expansion opacity formalism.Comment: 16 pages, ApJ accepte

SN 2008S: an electron capture SN from a super-AGB progenitor?

We present comprehensive photometric and spectroscopic observations of the faint transient SN 2008S discovered in NGC 6946. SN 2008S exhibited slow photometric evolution and almost no spectral variability during the first nine months, implying a high density CS medium. The light curve is similar in shape to that of SN 1998S and SN 1979C, although significantly fainter at maximum light. Our quasi-bolometric lightcurve extends to 300 days and shows a tail phase decay rate consistent with that of ^{56}Co. We propose that this is evidence for an explosion and formation of ^{56}Ni (0.0015 +/- 0.0004 M_Sun). The large MIR flux detected shortly after explosion can be explained by a light echo from pre-exisiting dust. The late NIR flux excess is plausibly due to a combination of warm newly-formed ejecta dust together with shock-heated dust in the CS environment. We reassess the progenitor object detected previously in Spitzer archive images, supplementing this discussion with a model of the MIR spectral energy distribution. This supports the idea of a dusty, optically thick shell around SN 2008S with an inner radius of nearly 90AU and outer radius of 450AU, and an inferred heating source of 3000 K and luminosity of L ~ 10^{4.6} L_Sun. The combination of our monitoring data and the evidence from the progenitor analysis leads us to support the scenario of a weak electron capture supernova explosion in a super-AGB progenitor star (of initial mass 6-8 M_sun) embedded within a thick CS gaseous envelope. We suggest that all of main properties of the electron capture SN phenomenon are observed in SN 2008S and future observations may allow a definitive answer.Comment: accepted for publication in MNRAS (2009 May 7

Prion infection impairs cholesterol metabolism in neuronal cells

Conversion of prion protein (PrPC) into a pathological isoform (PrPSc) during prion infection occurs in lipid rafts and is dependent on cholesterol. Here, we show that prion infection increases the abundance of cholesterol transporter, ATP-binding cassette transporter type A1 (ATP-binding cassette transporter type A1), but reduces cholesterol efflux from neuronal cells leading to the accumulation of cellular cholesterol. Increased abundance of ABCA1 in prion disease was confirmed in prion-infected mice. Mechanistically, conversion of PrPC to the pathological isoform led to PrPSc accumulation in rafts, displacement of ABCA1 from rafts and the cell surface, and enhanced internalization of ABCA1. These effects were abolished with reversal of prion infection or by loading cells with cholesterol. Stimulation of ABCA1 expression with liver X receptor agonist or overexpression of heterologous ABCA1 reduced the conversion of prion protein into the pathological form upon infection. These findings demonstrate a reciprocal connection between prion infection and cellular cholesterol metabolism, which plays an important role in the pathogenesis of prion infection in neuronal cells