Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOe4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOe2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond e2 and e4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

Signatures of delayed detonation, asymmetry, and electron capture in the mid-infrared spectra of supernovae 2003hv and 2005df

We present mid-infrared (5.2-15.2 mu m) spectra of the Type Ia supernovae (SNe Ia) 2003hv and 2005df observed with the Spitzer Space Telescope. These are the first observed mid-infrared spectra of thermonuclear supernovae, and show strong emission from fine-structure lines of Ni, Co, S, and Ar. The detection of Ni emission in SN 2005df 135 days after the explosion provides direct observational evidence of high-density nuclear burning forming a significant amount of stable Ni in a SN Ia. The SN 2005df Ar lines also exhibit a two-pronged emission profile, implying that the Ar emission deviates significantly from spherical symmetry. The spectrum of SN 2003hv also shows signs of asymmetry, exhibiting blueshifted [Co (III)], which matches the blueshift of [Fe (II)] lines in nearly coeval near-infrared spectra. Finally, local thermodynamic equilibrium abundance estimates for the yield of radioactive Ni-56 give M-56Ni approximate to 0.5 M-circle dot, for SN 2003hv, but only M-56Ni approximate to 0.13-0.22 M-circle dot for the apparently subluminous SN 2005df, supporting the notion that the luminosity of SNe Ia is primarily a function of the radioactive 56Ni yield. The observed emission-line profiles in the SN 2005df spectrum indicate a chemically stratified ejecta structure, which matches the predictions of delayed detonation (DD) models, but is entirely incompatible with current three-dimensional deflagration models. Furthermore, the degree that this layering persists to the innermost regions of the supernova is difficult to explain even in a DD scenario, where the innermost ejecta are still the product of deflagration burning. Thus, while these results are roughly consistent with a delayed detonation, it is clear that a key piece of physics is still missing from our understanding of the earliest phases of SN Ia explosions.

ESC observations of SN 2005cf - I. Photometric evolution of a normal Type Ia supernova

We present early-time optical and near-infrared photometry of supernova (SN) 2005cf. The observations, spanning a period from about 12 d before to 3 months after maximum, have been obtained through the coordination of observational efforts of various nodes of the European Supernova Collaboration and including data obtained at the 2-m Himalayan Chandra Telescope. From the observed light curve we deduce that SN 2005cf is a fairly typical SN Ia with a post-maximum decline [Delta m(15)(B)(true) = 1.12] close to the average value and a normal luminosity of M-B,M-max = -19.39 +/- 0.33. Models of the bolometric light curve suggest a synthesized Ni-56 mass of about 0.7 M-circle dot. The negligible host galaxy interstellar extinction and its proximity make SN 2005cf a good Type Ia SN template.

ESC and KAIT observations of the transitional type Ia SN 2004eo

We present optical and infrared observations of the unusual Type Ia supernova (SN) 2004eo. The light curves and spectra closely resemble those of the prototypical SN 1992A, and the luminosity at maximum (M-B = -19.08) is close to the average for a Type Ia supernova (SN Ia). However, the ejected Ni-56 mass derived by modelling the bolometric light curve (about 0.45M(circle dot)) lies near the lower limit of the Ni-56 mass distribution observed in normal SNe Ia. Accordingly, SN 2004eo shows a relatively rapid post-maximum decline in the light curve [Delta m(15)(B)(true) = 1.46], small expansion velocities in the ejecta and a depth ratio Si II lambda 5972/ Si II lambda 6355 similar to that of SN 1992A. The physical properties of SN 2004eo cause it to fall very close to the boundary between the faint, low-velocity gradient and high-velocity gradient subgroups proposed by Benetti et al. Similar behaviour is seen in a few other SNe Ia. Thus, there may in fact exist a few SNe Ia with intermediate physical properties.

Anomalous extinction behaviour towards the type Ia SN 2003cg

We present optical and near-infrared photometry and spectroscopy of the Type Ia SN 2003cg, which exploded in the nearby galaxy NGC 3169. The observations cover a period between -8.5 and +414 d post-maximum. SN 2003cg is a normal but highly reddened Type Ia event. Its B magnitude at maximum B-max = 15.94 +/- 0.04 and Delta m(15)(B)(obs) = 1.12 +/- 0.04 [Delta m(15)(B)(intrinsic) = 1.25 +/- 0.05]. Allowing R-V to become a free parameter within the Cardelli et al. extinction law, simultaneous matches to a range of colour curves of normal SNe Ia yielded E(B - V) = 1.33 +/- 0.11, and RV = 1.80 +/- 0.19. While the value obtained for R-V is small, such values have been invoked in the past, and may imply a grain size which is small compared with the average value for the local interstellar medium.

Early-time Spitzer observations of the type II plateau supernova SN 2004dj

We present mid-infrared observations with the Spitzer Space Telescope of the nearby Type II-P supernova SN 2004dj at epochs of 89 - 129 days. We have obtained the first mid-IR spectra of any supernova apart from SN 1987A. A prominent [Ni II] 6.64 mu m line is observed, from which we deduce that the mass of stable nickel must be at least 2.2 x 10(-4) M-.. We also observe the red wing of the CO fundamental band. We relate our findings to possible progenitors and favor an evolved star, most likely a red supergiant, with a probable initial mass between similar to 10 and 15 M-..

Apo J/clusterin expression and secretion: Evidence for 15-deoxy-Δ12,14-PGJ2-dependent mechanism

Cyclooxygenase-2 (Cox-2) and Apo J/clusterin are involved in inflammatory resolution and have each been reported to inhibit NF-?B signalling. Using a well-validated rat pheochromocytoma (PC12) cell culture model of Cox-2 over-expression the current study investigated inter-dependence between Cox-2 and clusterin with respect to induction of expression and impact on NF-?B signalling. Both gene expression and immunoblot analysis confirmed that intracellular and secreted levels of clusterin were elevated in Cox-2 over-expressing cells (PCXII). Clusterin expression was increased in control (PCMT) cells in a time- and dose-dependent manner by 15-deoxy-? 12,14-prostaglandin J 2 (15d-PGJ 2), but not PGE 2, and inhibited in PCXII cells by pharmacological Cox inhibition. In PCXII cells, inhibition of two transcription factors known to be activated by 15d-PGJ 2, heat shock factor 1 (HSF-1) and peroxisome proliferator activated receptor (PPAR)?, by transcription factor oligonucleotide decoy and antagonist (GW9662) treatment, respectively, reduced clusterin expression. While PCXII cells exhibited reduced TNF-a-induced cell surface ICAM-1 expression, IkB phosphorylation and degradation were similar to control cells. With respect to the impact of Cox-2-dependent clusterin upregulation on NF-?B signalling, basal levels of I?B were similar in control and PCXII cells, and no evidence for a physical association between clusterin and phospho-I?B was obtained. Moreover, while PCXII cells exhibited reduced NF-?B transcriptional activity, this was not restored by clusterin knock-down. These results indicate that Cox-2 induces clusterin in a 15d-PGJ 2-dependent manner, and via activation of HSF-1 and PPAR?. However, the results do not support a model whereby Cox-2/15d-PGJ 2-dependent inhibition of NF-?B signalling involves clusterin.

The DCN/HCN abundance ratio in hot molecular cores

We have observed the 3-2 transitions of DCN and (HCN)-N-15 in a number of hot molecular cores previously surveyed by us with the interesting result that the DCN/HCN ratio is low, a few times 10(-3), in the hot cores. The abundance ratio of DCN/HCN is derived both 'on-core' and 'off-core' and, in general is larger at the 'off-core' positions. Comparision with chemical models of these sources indicates that DCN liberated from evaporated ices can be destroyed rapidly in the hot gas by reaction with atomic hydrogen, which works to reset the the initial DCN/HCN ratio in the ice to the gas-phase atomic D/H ratio. The low DCN/HCN abundance ratio we measure can be reached in less than 10(4) years, consistent with previous estimates of the core ages, if the activation energy of the reaction is less than 500 K.

A 330-360 GHz spectral survey of G34.3+0.15 .2. Chemical modelling

We describe a detailed depth-and time-dependent model of the molecular cloud associated with the ultracompact H II region G 34.3+0.15. Previous work on observations of NH3 and CS indicates that the molecular cloud has three distinct physical components:- an ultracompact hot core, a compact hot core and an extended halo. We have used the physical parameters derived from these observations as input to our detailed chemical kinetic modelling. The results of the model calculations are discussed with reference to the different chemistries occuring in each component and are compared with abundances derived from our recent spectral line survey of G 34.3+0.15 (Paper I).

A 330-360 GHz spectral survey of G 34.3+0.15 .1. Data and physical analysis

A 330--360 GHz spectral survey of the hot molecular core associated with the 'cometary' ultracompact HII region G 34.3+/-0.15 observed with the James Clerk Maxwell Telescope has detected 338 spectral lines from at least 35 distinct chemical species plus 19 isotopomers. 70 lines remain unidentified. Chemical abundance and rotation temperature have been determined by rotation diagram analysis for 12 species, and lower limits to abundance found for 38 others.

THE DETECTION OF HOT ETHANOL IN G34.3+0.15

Hot molecular cores in star-forming regions are known to have gas-phase chemical compositions determined by the evaporation of material from the icy mantles of interstellar grains, followed by subsequent reactions in the gas phase. Current models suggest that the evaporated material is rich in hydrogenated species, such as water, methane and methanol. In this paper, we report the detection of 14 rotational transitions of ethanol in the submillimetre spectrum of the molecular cloud associated with the ultra-compact H II region G34.3+0.15. We derive a rotation temperature of 125 K and a beam-averaged column density of 2.0x10(15) cm(-2), corresponding to a fractional abundance on the order of 4x10(-9). This large abundance, which is a lower limit due to the likelihood of beam dilution, cannot be made by purely gas-phase processes, and we conclude that the ethanol must be formed efficiently in the grain surface chemistry. Since it has been argued previously that methanol is formed via surface chemistry, it appears that alcohol formation may be a natural by-product of surface reactions.

WASP-41b: A Transiting Hot Jupiter Planet Orbiting a Magnetically Active G8V Star

We report the discovery of a transiting planet with an orbital period of 3.05 days orbiting the star TYC 7247-587-1. The star, WASP-41, is a moderately bright G8 V star (V=11.6) with a metallicity close to solar ([Fe/H]=-0.08±0.09). The star shows evidence of moderate chromospheric activity, both from emission in the cores of the Ca ii H and K ines and photometric variability with a period of 18.4 days and an amplitude of about 1%. We use a new method to show quantitatively that this periodic signal has a low false-alarm probability. The rotation period of the star implies a gyrochronological age for WASP-41 of 1.8 Gyr with an error of about 15%. We have used a combined analysis of the available photometric and spectroscopic data to derive the mass and radius of the planet (0.92±0.06 M, 1.20±0.06 R). Further observations of WASP-41 can be used to explore the connections between the properties of hot Jupiter planets and the level of chromospheric activity in their host stars.

The spin-orbit angles of the transiting exoplanets WASP-1b, WASP-24b, WASP-38b and HAT-P-8b from Rossiter-McLaughlin observations

We present observations of the Rossiter–McLaughlin effect for the transiting exoplanets WASP-1b, WASP-24b, WASP-38b and HAT-P-8b, and deduce the orientations of the planetary orbits with respect to the host stars’ rotation axes. The planets WASP-24b, WASP-38b and HAT-P-8b appear to move in prograde orbits and be well aligned, having sky-projected spin-orbit angles consistent with zero: λ=−4°.7 ± 4°.0, 15°+33−43 and Graphic, respectively. The host stars have Teff < 6250 K and conform with the trend of cooler stars having low obliquities. WASP-38b is a massive planet on a moderately long period, eccentric orbit so may be expected to have a misaligned orbit given the high obliquities measured in similar systems. However, we find no evidence for a large spin-orbit angle. By contrast, WASP-1b joins the growing number of misaligned systems and has an almost polar orbit, λ=Graphic. It is neither very massive, eccentric nor orbiting a hot host star, and therefore does not share the properties of many other misaligned systems.

WASP-50 b: a hot Jupiter transiting a moderately active solar-type star

We report the discovery by the WASP transit survey of a giant planet in a close orbit (0.0295 ± 0.0009 AU) around a moderately bright (V = 11.6, K = 10) G9 dwarf (0.89 ± 0.08 Msun, 0.84 ± 0.03 Rsun) in the Southern constellation Eridanus. Thanks to high-precision follow-up photometry and spectroscopy obtained by the telescopes TRAPPIST and Euler, the mass and size of this planet, WASP-50 b, are well constrained to 1.47 ± 0.09 MJup and 1.15 ± 0.05 RJup, respectively. The transit ephemeris is 2 455 558.6120 (±0.0002) + N × 1.955096 (±0.000005) HJDUTC. The size of the planet is consistent with basic models of irradiated giant planets. The chromospheric activity (log R'HK = -4.67) and rotational period (Prot = 16.3 ± 0.5 days) of the host star suggest an age of 0.8 ± 0.4 Gy that is discrepant with a stellar-evolution estimate based on the measured stellar parameters (?* = 1.48 ± 0.10 ?sun, Teff = 5400 ± 100 K, [Fe/H] = -0.12 ± 0.08) which favors an age of 7 ± 3.5 Gy. This discrepancy could be explained by the tidal and magnetic influence of the planet on the star, in good agreement with the observations that stars hosting hot Jupiters tend to show faster rotation and magnetic activity. We measure a stellar inclination of 84-31+6 deg, disfavoring a high stellar obliquity. Thanks to its large irradiation and the relatively small size of its host star, WASP-50 b is a good target for occultation spectrophotometry, making it able to constrain the relationship between hot Jupiters' atmospheric thermal profiles and the chromospheric activity of their host stars. The photometric time-series used in this work are only available at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/533/A88