On the origin of variable structures in the winds of hot luminous stars

Examination of the temporal variability properties of several strong optical recombination lines in a large sample of Galactic Wolf-Rayet (WR) stars reveals possible trends, especially in the more homogeneous WC than the diverse WN subtypes, of increasing wind variability with cooler subtypes. This could imply that a serious contender for the driver of the variations is stochastic, magnetic subsurface convection associated with the 170 kK partial-ionization zone of iron, which should occupy a deeper and larger zone of greater mass in cooler WR subtypes. This empirical evidence suggests that the heretofore proposed ubiquitous driver of wind variability, radiative instabilities, may not be the only mechanism playing a role in the stochastic multiple small-scaled structures seen in the winds of hot luminous stars. In addition to small-scale stochastic behaviour, subsurface convection guided by a global magnetic field with localized emerging loops may also be at the origin of the large-scale corotating interaction regions as seen frequently in O stars and occasionally in the winds of their descendant WR stars.Comment: 8 pages, 2 figures and 2 tables. Monthly Notices of the Royal Astronomical Society 201

Diagnostic of the unstable envelopes of Wolf-Rayet stars

The envelopes of stars near the Eddington limit are prone to various instabilities. A high Eddington factor in connection with the Fe opacity peak leads to convective instability, and a corresponding envelope inflation may induce pulsational instability. Here, we investigate the occurrence and consequences of both instabilities in models of Wolf-Rayet stars. We determine the convective velocities in the sub-surface convective zones to estimate the amplitude of the turbulent velocity at the base of the wind that potentially leads to the formation of small-scale wind structures, as observed in several WR stars. We also investigate the effect of mass loss on the pulsations of our models. We approximated solar metallicity WR stars by models of mass-losing helium stars, and we characterized the properties of convection in the envelope adopting the standard MLT. Our results show the occurrence of sub-surface convective regions in all studied models. Small surface velocity amplitudes are predicted for models with masses below 10Msun. For models with M>10Msun, the surface velocity amplitudes are of the order of 10km/s. Moreover we find the occurrence of pulsations for stars in the mass range 9-14Msun, while mass loss appears to stabilize the more massive WR stars. We confront our results with observationally derived line variabilities of 17 WN stars. The data suggest variability to occur for stars above 10Msun, which is increasing linearly with mass above this value, in agreement with our results. We further find some of our models to be unstable to radial pulsations, and predict local magnetic fields of the order of hundreds of Gauss in WR stars more massive than 10Msun. Our study relates the surface velocity fluctuations induced by sub-surface convection to the formation of clumping in the inner part of the wind. From this mechanism, we expect a stronger variability in more massive WR stars.Comment: A&A, accepte

Open cluster candidates in the VVVX area: VVVX CL 076 and CL 077

We are reporting some basic parameters of two newly discovered clusters, VVVX CL 076 and CL 077, recently discovered in the galactic disk area covered by the VISTA Variables in the Via Lactea eXtended (VVVX) ESO Public Survey. The preliminary analysis shows that both clusters are young and relatively close to the Sun.Peer reviewedFinal Published versio

FSR 1716: A New Milky Way Globular Cluster Confirmed Using VVV RR Lyrae Stars

We use deep multi-epoch near-IR images of the VISTA Variables in the Vía Láctea (VVV) Survey to search for RR Lyrae stars toward the Southern Galactic plane. Here, we report the discovery of a group of RR Lyrae stars close together in VVV tile d025. Inspection of the VVV images and PSF photometry reveals that most of these stars are likely to belong to a globular cluster that matches the position of the previously known star cluster FSR 1716. The stellar density map of the field yields a >100? detection for this candidate globular cluster that is centered at equatorial coordinates R.A. J2000 = 16:10:30.0, decl. J2000 = ?53:44:56 and galactic coordinates l = 329.77812, b = ?1.59227. The color–magnitude diagram of this object reveals a well-populated red giant branch, with a prominent red clump at K s = 13.35 ± 0.05, and J ? K s = 1.30 ± 0.05. We present the cluster RR Lyrae positions, magnitudes, colors, periods, and amplitudes. The presence of RR Lyrae indicates an old globular cluster, with an age >10 Gyr. We classify this object as an Oosterhoff type I globular cluster, based on the mean period of its RR Lyrae type ab, $\langle P\rangle =0.540$ days, and argue that this is a relatively metal-poor cluster with [Fe/H] = ?1.5 ± 0.4 dex. The mean extinction and reddening for this cluster are ${A}_{{K}_{s}}=0.38\pm 0.02$ and E(J ? K s ) = 0.72 ± 0.02 mag, respectively, as measured from the RR Lyrae colors and the near-IR color–magnitude diagram. We also measure the cluster distance using the RR Lyrae type ab stars. The cluster mean distance modulus is (m ? M)0 = 14.38 ± 0.03 mag, implying a distance D = 7.5 ± 0.2 kpc and a Galactocentric distance R G = 4.3 kpc

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Accreting Black Holes Skewing and Bending the Optical Emission from Massive Wolf-Rayet Companions -- A Case Study of IC10 X-1

We present a statistical analysis of the He ii 4686 emission line in the spectra of the black hole and Wolf-Rayet (WR) star of the high-mass X-ray binary IC10 X-1. This line is visibly skewed, and the third moment (skewness) varies with the binary's orbital phase. We describe a new method of extracting such weak/faint features lying barely above a noisy continuum. Using the moments of these features, we have been able to decompose these skewed lines into two symmetric Gaussian profiles as a function of the orbital phase. The astrophysical implications of this decomposition are significant due to the complex nature of wind-accretion stream interactions in such binary systems. Previous studies have already shown a 0.25 phase lag in the radial velocity curve of the star and the X-ray eclipse, which indicates that the He ii emitters might be in the stellar wind, hence not tracing the star's orbital motion. Results from this work further suggest the existence of two separate emitting regions, one in the stellar wind in the shadow of the WR star, and another in the accretion stream that impacts the black hole's outer accretion disk; and the observed skewed He ii lines can be reproduced by superposition of the two corresponding time-dependent Gaussian emission profiles.Comment: 13 pages, 5 figures, accepted for publication in MNRAS Journa

GRACES observations of young [α/Fe]-rich stars

We measure chemical abundance ratios and radial velocities in four massive (i.e. young) [α/Fe]-rich red giant stars using high-resolution high-S/N spectra from ESPaDOnS fed by Gemini-GRACES. Our differential analysis ensures that our chemical abundances are on the same scale as the Alves-Brito et al. (2010) study of bulge, thin, and thick disc red giants. We confirm that the program stars have enhanced [α/Fe] ratios and are slightly metal poor. Aside from lithium enrichment in one object, the program stars exhibit no chemical abundance anomalies when compared to giant stars of similar metallicity throughout the Galaxy. This includes the elements Li, O, Si, Ca, Ti, Cr, Ni, Cu, Ba, La, and Eu. Therefore, there are no obvious chemical signatures that can help to reveal the origin of these unusual stars. While our new observations show that only one star (not the Li-rich object) exhibits a radial velocity variation, simulations indicate that we cannot exclude the possibility that all four could be binaries. In addition, we find that two (possibly three) stars show evidence for an infrared excess, indicative of a debris disc. This is consistent with these young [α/Fe]-rich stars being evolved blue stragglers, suggesting their apparent young age is a consequence of a merger or mass transfer. We would expect a binary fraction of ~50 per cent or greater for the entire sample of these stars, but the signs of the circumbinary disc may have been lost since these features can have short time-scales. Radial velocity monitoring is needed to confirm the blue straggler origin.This work is based on observations obtained with ESPaDOnS, located at the Canada-France-Hawaii Telescope (CFHT). CFHT is operated by the National Research Council of Canada, the Institut National des Sciences de l'Univers of the Centre National de la Recherche Scientique of France, and the University of Hawai'i. ESPaDOnS is a collaborative project funded by France (CNRS, MENESR, OMP, LATT), Canada (NSERC), CFHT, and ESA. ESPaDOnS was remotely controlled from the Gemini Observatory, which is operated by the Association of Universities for Research in Astronomy, Inc., under a cooperative agreement with the NSF on behalf of the Gemini partnership: the National Science Foundation (United States), the National Research Council (Canada), CONICYT (Chile), the Australian Research Council (Australia), Ministério da Ciência, Tecnologia e Inovaç ao (Brazil), and Ministerio de Ciencia, Tecnología e Innovación Productiva (Argentina). We thank the anonymous referee for helpful comments. DY thanks John E. Norris for helpful discussions. DY, LC, MA, AD, and KS gratefully acknowledge support from the Australian Research Council (grants FL110100012, DP120100991, FT140100554, and DP150100250). SMgratefully acknowledges support from the Australian Research Council (grant DE 140100598). JMthanks support by FAPESP (2010/50930-6)

Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response : a sub-study of the NEAT001/ANRS143 randomized trial

OBJECTIVES: NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. METHODS: Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0-24 and C24 with time to virological failure was evaluated by Cox regression. RESULTS: Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P < 0.001). No significant relationship was demonstrated between darunavir AUC0-24 or C24 and time to virological failure [HR (95% CI): 2.28 (0.53-9.80), P = 0.269; and 1.82 (0.61-5.41), P = 0.279, respectively]. CONCLUSIONS: Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity