Intrinsic Absorption in the Spectrum of NGC 7469: Simultaneous Chandra, FUSE, and STIS Observations

We present simultaneous X-ray, far-ultraviolet, and near-ultraviolet spectra of the Seyfert 1 galaxy NGC 7469 obtained with the Chandra X-Ray Observatory, the Far Ultraviolet Spectroscopic Explorer, and the Space Telescope Imaging Spectrograph on the Hubble Space Telescope. Previous non-simultaneous observations of this galaxy found two distinct UV absorption components, at -560 and -1900 km/s, with the former as the likely counterpart of the X-ray absorber. We confirm these two absorption components in our new UV observations, in which we detect prominent O VI, Ly alpha, N V, and C IV absorption. In our Chandra spectrum we detect O VIII emission, but no significant O VIII or O VII absorption. We also detect a prominent Fe K alpha emission line in the Chandra spectrum, as well as absorption due to hydrogen-like and helium-like neon, magnesium, and silicon at velocities consistent with the -560 km/s UV absorber. The FUSE and STIS data reveal that the H I and C IV column densities in this UV- and X-ray- absorbing component have increased over time, as the UV continuum flux decreased. We use measured H I, N V, C IV, and O VI column densities to model the photoionization state of both absorbers self-consistently. We confirm the general physical picture of the outflow in which the low velocity component is a highly ionized, high density absorber with a total column density of 10^20 cm^-2, located near the broad emission line region, although due to measurable columns of N V and C IV, we assign it a somewhat smaller ionization parameter than found previously, U~1. The high velocity UV component is of lower density, log N=18.6, and likely resides farther from the central engine as we find its ionization parameter to be U=0.08.Comment: Minor correction to abstract; STScI eprint #1683; 50 pages, incl. 19 figures, 4 tables; Accepted to Ap

The Ionized Gas and Nuclear Environment in NGC 3783 V. Variability and Modeling of the Intrinsic Ultraviolet Absorption

We present results on the location, physical conditions, and geometry of the outflow in the Seyfert 1 galaxy NGC 3783 from a study of the variable intrinsic UV absorption. Based on 18 observations with HST/STIS and 6 observations with FUSE, we find: 1) The absorption from the lowest-ionization species in each of the three strong kinematic components varied inversely with the continuum flux, indicating the ionization structure responded to changes in the photoionizing flux over the weekly timescales sampled by our observations. 2) A multi- component model with an unocculted NLR and separate BLR and continuum line-of-sight covering factors predicts saturation in several lines, consistent with the lack of observed variability. 3) Column densities for the individual metastable levels are measured from the resolved C III *1175 absorption complex observed in one component. Based on our computed metastable level populations, the electron density of this absorber is ~3x10^4 cm^-3. Photoionization modeling results place it at ~25 pc from the central source. 4) Using time-dependent calculations, we are able to reproduce the detailed variability observed in this absorber, and derive upper limits on the distances for the other components of 25-50 pc. 5) The ionization parameters derived for the higher ionization UV absorbers are consistent with the modeling results for the lowest-ionization X-ray component, but with smaller total column density. They have similar pressures as the three X-ray ionization components. These results are consistent with an inhomogeneous wind model for the outflow in NGC 3783. 6) Based on the predicted emission-line luminosities, global covering factor constraints, and distances derived for the UV absorbers, they may be identified with emission- line gas observed in the inner NLR of AGNs. (abridged)Comment: 30 pages, 18 figures (7 color), emulateapj, accepted for publication in The Astrophysical Journa

Intrinsic aerobic capacity sets a divide for aging and longevity

<p><b>Rationale:</b> Low aerobic exercise capacity is a powerful predictor of premature morbidity and mortality for healthy adults as well as those with cardiovascular disease. For aged populations, poor performance on treadmill or extended walking tests indicates closer proximity to future health declines. Together, these findings suggest a fundamental connection between aerobic capacity and longevity.</p> <p><b>Objectives:</b> Through artificial selective breeding, we developed an animal model system to prospectively test the association between aerobic exercise capacity and survivability (aerobic hypothesis).</p> <p><b>Methods and Results:</b> Laboratory rats of widely diverse genetic backgrounds (N:NIH stock) were selectively bred for low or high intrinsic (inborn) treadmill running capacity. Cohorts of male and female rats from generations 14, 15, and 17 of selection were followed for survivability and assessed for age-related declines in cardiovascular fitness including maximal oxygen uptake (VO<sub>2max</sub>), myocardial function, endurance performance, and change in body mass. Median lifespan for low exercise capacity rats was 28% to 45% shorter than high capacity rats (hazard ratio, 0.06; P<0.001). VO<sub>2max</sub>, measured across adulthood was a reliable predictor of lifespan (P<0.001). During progression from adult to old age, left ventricular myocardial and cardiomyocyte morphology, contractility, and intracellular Ca<sup>2+</sup> handling in both systole and diastole, as well as mean blood pressure, were more compromised in rats bred for low aerobic capacity. Physical activity levels, energy expenditure (Vo<sub>2</sub>), and lean body mass were all better sustained with age in rats bred for high aerobic capacity.</p> <p><b>Conclusions:</b> These data obtained from a contrasting heterogeneous model system provide strong evidence that genetic segregation for aerobic exercise capacity can be linked with longevity and are useful for deeper mechanistic exploration of aging.</p&gt

Intrinsic Absorption in the Spectrum of Mrk 279: Simultaneous Chandra, FUSE, and STIS Observations

We present a study of the intrinsic X-ray and far-ultraviolet absorption in the Seyfert 1.5 galaxy Markarian 279 using simultaneous observations from the Chandra X-ray Observatory, the Space Telescope Imaging Spectrograph aboard the Hubble Space Telescope, and the Far Ultraviolet Spectroscopic Explorer (FUSE). We also present FUSE observations made at three additional epochs. We detect the Fe K-alpha emission line in the Chandra spectrum, and its flux is consistent with the low X-ray continuum flux level of Mrk 279 at the time of the observation. Due to low signal-to-noise ratios in the Chandra spectrum, no O VII or O VIII absorption features are observable in the Chandra data, but the UV spectra reveal strong and complex absorption from HI and high-ionization species such as O VI, N V, and C IV, as well as from low-ionization species such as C III, N III, C II, and N II in some velocity components. The far-UV spectral coverage of the FUSE data provides information on high-order Lyman series absorption, which we use to calculate the optical depths and line and continuum covering fractions in the intrinsic HI absorbing gas in a self-consistent fashion. The UV continuum flux of Mrk 279 decreases by a factor of ~7.5 over the time spanning these observations and we discuss the implications of the response of the absorption features to this change. From arguments based on the velocities, profile shapes, covering fractions and variability of the UV absorption, we conclude that some of the absorption components, particularly those showing prominent low-ionization lines, are likely associated with the host galaxy of Mrk 279, and possibly with its interaction with a close companion galaxy, while the remainder arises in a nuclear outflow.Comment: To appear in 2004 May ApJS; double-column format; 58 pages, incl. 29 figures, 9 tables; minor changes to tex

The Ionized Gas and Nuclear Environment in NGC 3783 II. Averaged HST/STIS and FUSE Spectra

We present observations of the intrinsic absorption in the Seyfert 1 galaxy NGC 3783 obtained with the STIS/HST and FUSE. We have coadded multiple STIS and FUSE observations to obtain a high S/N averaged spectrum spanning 905-1730 A. The averaged spectrum reveals absorption in O VI, N V, C IV, N III, C III and the Lyman lines up to LyE in the three blueshifted kinematic components previously detected in the STIS spectrum (at radial velocities of -1320, -724, and -548 km/s). The highest velocity component exhibits absorption in Si IV. We also detect metastable C III* in this component, indicating a high density in this absorber. We separate the individual covering factors of the continuum and emission-line sources as a function of velocity in each kinematic component using the LyA and LyB lines. Additionally, we find that the continuum covering factor varies with velocity within the individual kinematic components, decreasing smoothly in the wings of the absorption by at least 60%. The covering factor of Si IV is found to be less than half that of H I and N V in the high velocity component. Additionally, the FWHM of N III and Si IV are narrower than the higher ionization lines in this component. These results indicate there is substructure within this absorber. We derive a lower limit on the total column (N_H>=10^{19}cm^{-2}) and ionization parameter (U>=0.005) in the low ionization subcomponent of this absorber. The metastable-to-total C III column density ratio implies n_e~10^9 cm^{-3} and an upper limit on the distance of the absorber from the ionizing continuum of R<=8x10^{17} cm.Comment: 29 pages, 8 figures (Figures 1-3 are in color), Accepted for pulication in the Astrophysical Journa

A CFTR Potentiator in Patients with Cystic Fibrosis and the G551D Mutation

BACKGROUND: Increasing the activity of defective cystic fibrosis transmembrane conductance regulator (CFTR) protein is a potential treatment for cystic fibrosis. METHODS: We conducted a randomized, double-blind, placebo-controlled trial to evaluate ivacaftor (VX-770), a CFTR potentiator, in subjects 12 years of age or older with cystic fibrosis and at least one G551D-CFTR mutation. Subjects were randomly assigned to receive 150 mg of ivacaftor every 12 hours (84 subjects, of whom 83 received at least one dose) or placebo (83, of whom 78 received at least one dose) for 48 weeks. The primary end point was the estimated mean change from baseline through week 24 in the percent of predicted forced expiratory volume in 1 second (FEV(1)). RESULTS: The change from baseline through week 24 in the percent of predicted FEV(1) was greater by 10.6 percentage points in the ivacaftor group than in the placebo group (P<0.001). Effects on pulmonary function were noted by 2 weeks, and a significant treatment effect was maintained through week 48. Subjects receiving ivacaftor were 55% less likely to have a pulmonary exacerbation than were patients receiving placebo, through week 48 (P<0.001). In addition, through week 48, subjects in the ivacaftor group scored 8.6 points higher than did subjects in the placebo group on the respiratory-symptoms domain of the Cystic Fibrosis Questionnaire–revised instrument (a 100-point scale, with higher numbers indicating a lower effect of symptoms on the patient’s quality of life) (P<0.001). By 48 weeks, patients treated with ivacaftor had gained, on average, 2.7 kg more weight than had patients receiving placebo (P<0.001). The change from baseline through week 48 in the concentration of sweat chloride, a measure of CFTR activity, with ivacaftor as compared with placebo was −48.1 mmol per liter (P<0.001). The incidence of adverse events was similar with ivacaftor and placebo, with a lower proportion of serious adverse events with ivacaftor than with placebo (24% vs. 42%). CONCLUSIONS: Ivacaftor was associated with improvements in lung function at 2 weeks that were sustained through 48 weeks. Substantial improvements were also observed in the risk of pulmonary exacerbations, patient-reported respiratory symptoms, weight, and concentration of sweat chloride

Inhibition of apoptosis in neuronal cells infected with Chlamydophila (Chlamydia) pneumoniae

Background Chlamydophila (Chlamydia) pneumoniae is an intracellular bacterium that has been identified within cells in areas of neuropathology found in Alzheimer disease (AD), including endothelia, glia, and neurons. Depending on the cell type of the host, infection by C. pneumoniae has been shown to influence apoptotic pathways in both pro- and anti-apoptotic fashions. We have hypothesized that persistent chlamydial infection of neurons may be an important mediator of the characteristic neuropathology observed in AD brains. Chronic and/or persistent infection of neuronal cells with C. pneumoniae in the AD brain may affect apoptosis in cells containing chlamydial inclusions. Results SK-N-MC neuroblastoma cells were infected with the respiratory strain of C. pneumoniae, AR39 at an MOI of 1. Following infection, the cells were either untreated or treated with staurosporine and then examined for apoptosis by labeling for nuclear fragmentation, caspase activity, and membrane inversion as indicated by annexin V staining. C. pneumoniae infection was maintained through 10 days post-infection. At 3 and 10 days post-infection, the infected cell cultures appeared to inhibit or were resistant to the apoptotic process when induced by staurosporine. This inhibition was demonstrated quantitatively by nuclear profile counts and caspase 3/7 activity measurements. Conclusion These data suggest that C. pneumoniae can sustain a chronic infection in neuronal cells by interfering with apoptosis, which may contribute to chronic inflammation in the AD brai

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes