Evidence for variability time-scale-dependent UV/X-ray delay in Seyfert 1 AGN NGC 7469

MP acknowledges Royal Society-SERB Newton International Fellowship support funded jointly by the Royal Society, UK and the Science and Engineering Board of India (SERB) through Newton–Bhabha Fund. IMcH acknowledges support from a Royal Society Leverhulme Trust Research Fellowship LT160006 and from STFC grant ST/M001326/1. EMC gratefully acknowledges support from the National Science Foundation through award number AST-1909199. KH acknowledges support from STFC grant ST/R000824/1.Using a month-long X-ray light curve from RXTE/PCA and 1.5 month-long UV continuum light curves from IUE spectra in 1220-1970 Å, we performed a detailed time-lag study of the Seyfert 1 galaxy NGC 7469. Our cross-correlation analysis confirms previous results showing that the X-rays are delayed relative to the UV continuum at 1315 Å by 3.49 ± 0.22 d, which is possibly caused by either propagating fluctuation or variable Comptonization. However, if variations slower than 5 d are removed from the X-ray light curve, the UV variations then lag behind the X-ray variations by 0.37 ± 0.14 d, consistent with reprocessing of the X-rays by a surrounding accretion disc. A very similar reverberation delay is observed between Swift/XRT X-ray and Swift/UVOT UVW2, U light curves. Continuum light curves extracted from the Swift/GRISM spectra show delays with respect to X-rays consistent with reverberation. Separating the UV continuum variations faster and slower than 5 d, the slow variations at 1825 Å lag those at 1315 Å by 0.29 ± 0.06 d, while the fast variations are coincident (0.04 ± 0.12 d). The UV/optical continuum reverberation lag from IUE, Swift, and other optical telescopes at different wavelengths are consistent with the relationship: τ ∝  λ4/3, predicted for the standard accretion disc theory while the best-fitting X-ray delay from RXTE and Swift/XRT shows a negative X-ray offset of ∼0.38 d from the standard disc delay prediction.Publisher PDFPeer reviewe

XRate: a fast prototyping, training and annotation tool for phylo-grammars

BACKGROUND: Recent years have seen the emergence of genome annotation methods based on the phylo-grammar, a probabilistic model combining continuous-time Markov chains and stochastic grammars. Previously, phylo-grammars have required considerable effort to implement, limiting their adoption by computational biologists. RESULTS: We have developed an open source software tool, xrate, for working with reversible, irreversible or parametric substitution models combined with stochastic context-free grammars. xrate efficiently estimates maximum-likelihood parameters and phylogenetic trees using a novel "phylo-EM" algorithm that we describe. The grammar is specified in an external configuration file, allowing users to design new grammars, estimate rate parameters from training data and annotate multiple sequence alignments without the need to recompile code from source. We have used xrate to measure codon substitution rates and predict protein and RNA secondary structures. CONCLUSION: Our results demonstrate that xrate estimates biologically meaningful rates and makes predictions whose accuracy is comparable to that of more specialized tools

Effect of kidney donation on bone mineral metabolism.

Kidney donation results in reductions in kidney function and lasting perturbations in phosphate homeostasis, which may lead to adverse cardiovascular sequelae. However, the acute effects of kidney donation on bone mineral parameters including regulators of calcium and phosphate metabolism are unknown. We conducted a prospective observational controlled study to determine the acute effects of kidney donation on mineral metabolism and skeletal health. Biochemical endpoints were determined before and after donation on days 1, 2 and 3, 6 weeks and 12 months in donors and at baseline, 6 weeks and 12 months in controls. Baseline characteristic of donors (n = 34) and controls (n = 34) were similar: age (53±10 vs 50±14 years, p = 0.33), BMI (26.3±2.89 vs 25.9±3.65, p = 0.59), systolic BP (128±13 vs 130±6 mmHg, p = 0.59), diastolic BP (80±9 vs 81±9 mmHg, p = 0.68) and baseline GFR (84.4±20.2 vs 83.6±25.2 ml/min/1.73m2, p = 0.89). eGFR reduced from 84.4±20.2 to 52.3±17.5 ml/min/1.73m2 (p<0.001) by day 1 with incomplete recovery by 12 months (67.7±22.6; p = 0.002). Phosphate increased by day 1 (1.1(0.9-1.2) to 1.3(1.1-1.4) mmol/L, p <0.001) but declined to 0.8(0.8-1.0) mmol/L (p<0.001) before normalizing by 6 weeks. Calcium declined on day 1 (p = 0.003) but recovered at 6 weeks or 12 months. PTH and FGF-23 remained unchanged, but α-Klotho reduced by day 1 (p = 0.001) and remained low at 6 weeks (p = 0.02) and 1 year (p = 0.04). In this study, we conclude that kidney donation results in acute disturbances in mineral metabolism characterised by a reduced phosphate and circulating α-Klotho concentration without acute changes in the phosphaturic hormones FGF23 and PTH

The Sloan Digital Sky Survey Reverberation Mapping Project: No Evidence for Evolution in the M-sigma Relation to z~1

We present host stellar velocity dispersion measurements for a sample of 88 broad-line quasars at 0.10.6) from the Sloan Digital Sky Survey Reverberation Mapping (SDSS-RM) project. High signal-to-noise ratio coadded spectra (average S/N~30 per 69 km/s pixel) from SDSS-RM allowed decomposition of the host and quasar spectra, and measurement of the host stellar velocity dispersions and black hole (BH) masses using the single-epoch (SE) virial method. The large sample size and dynamic range in luminosity (L5100=10^(43.2-44.7) erg/s) lead to the first clear detection of a correlation between SE virial BH mass and host stellar velocity dispersion far beyond the local universe. However, the observed correlation is significantly flatter than the local relation, suggesting that there are selection biases in high-z luminosity-threshold quasar samples for such studies. Our uniform sample and analysis enable an investigation of the redshift evolution of the M-sigma relation free of caveats by comparing different samples/analyses at disjoint redshifts. We do not observe evolution of the M-sigma relation in our sample, up to z~1, but there is an indication that the relation flattens towards higher redshifts. Coupled with the increasing threshold luminosity with redshift in our sample, this again suggests certain selection biases are at work, and simple simulations demonstrate that a constant M-sigma relation is favored to z~1. Our results highlight the scientific potential of deep coadded spectroscopy from quasar monitoring programs, and offer a new path to probe the co-evolution of BHs and galaxies at earlier times.Comment: replaced with the accepted version (minor changes and updated references); ApJ in press; changed title to highlight the main resul

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

A randomized, controlled, double-blind crossover study on the effects of isoeffective and isovolumetric intravenous crystalloid and gelatin on blood volume, and renal and cardiac hemodynamics

Background & aimsBlood volume expanding properties of colloids are superior to crystalloids. In addition to oncotic/osmotic properties, the electrolyte composition of infusions may have important effects on visceral perfusion, with infusions containing supraphysiological chloride causing hyperchloremic acidosis and decreased renal blood flow. In this non-inferiority study, a validated healthy human subject model was used to compare effects of colloid (4% succinylated gelatin) and crystalloid fluid regimens on blood volume, renal function, and cardiac output.MethodsHealthy male participants were given infusions over 60 min > 7 days apart in a randomized, crossover manner. Reference arm (A): 1.5 L of Sterofundin ISO, isoeffective arm (B): 0.5 L of 4% Gelaspan®, isovolumetric arm (C): 0.5 L of 4% Gelaspan® and 1 L of Sterofundin ISO (all B. Braun, Melsungen, Germany). Participants were studied over 240 min. Changes in blood volume were calculated from changes in weight and hematocrit. Renal volume, renal artery blood flow (RABF), renal cortex perfusion and diffusion, and cardiac index were measured with magnetic resonance imaging.ResultsTen of 12 males [mean (SE) age 23.9 (0.8) years] recruited, completed the study. Increase in body weight and extracellular fluid volume were significantly less after infusion B than infusions A and C, but changes in blood volume did not significantly differ between infusions. All infusions increased renal volume, with no significant differences between infusions. There was no significant difference in RABF across the infusion time course or between infusion types. Renal cortex perfusion decreased during the infusion (mean 18% decrease from baseline), with no significant difference between infusions. There was a trend for increased renal cortex diffusion (4.2% increase from baseline) for the crystalloid infusion. All infusions led to significant increases in cardiac index.ConclusionsA smaller volume of colloid (4% succinylated gelatin) was as effective as a larger volume of crystalloid at expanding blood volume, increasing cardiac output and changing renal function. Significantly less interstitial space expansion occurred with the colloid

Novel mutations in TARDBP (TDP-43) in patients with familial amyotrophic lateral sclerosis.

The TAR DNA-binding protein 43 (TDP-43) has been identified as the major disease protein in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin inclusions (FTLD-U), defining a novel class of neurodegenerative conditions: the TDP-43 proteinopathies. The first pathogenic mutations in the gene encoding TDP-43 (TARDBP) were recently reported in familial and sporadic ALS patients, supporting a direct role for TDP-43 in neurodegeneration. In this study, we report the identification and functional analyses of two novel and one known mutation in TARDBP that we identified as a result of extensive mutation analyses in a cohort of 296 patients with variable neurodegenerative diseases associated with TDP-43 histopathology. Three different heterozygous missense mutations in exon 6 of TARDBP (p.M337V, p.N345K, and p.I383V) were identified in the analysis of 92 familial ALS patients (3.3%), while no mutations were detected in 24 patients with sporadic ALS or 180 patients with other TDP-43-positive neurodegenerative diseases. The presence of p.M337V, p.N345K, and p.I383V was excluded in 825 controls and 652 additional sporadic ALS patients. All three mutations affect highly conserved amino acid residues in the C-terminal part of TDP-43 known to be involved in protein-protein interactions. Biochemical analysis of TDP-43 in ALS patient cell lines revealed a substantial increase in caspase cleaved fragments, including the approximately 25 kDa fragment, compared to control cell lines. Our findings support TARDBP mutations as a cause of ALS. Based on the specific C-terminal location of the mutations and the accumulation of a smaller C-terminal fragment, we speculate that TARDBP mutations may cause a toxic gain of function through novel protein interactions or intracellular accumulation of TDP-43 fragments leading to apoptosis

Quality control for multiple breath washout tests in multicentre bronchiectasis studies:Experiences from the BRONCH-UK clinimetrics study

Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or “over-reading” is resource intensive and the impact is unclear. Objectives: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. Methods: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. Results: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. Conclusion: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW

Understanding water and energy fluxes in the Amazonia: Lessons from an observation-model intercomparison

Tropical forests are an important part of global water and energy cycles, but the mechanisms that drive seasonality of their land-atmosphere exchanges have proven challenging to capture in models. Here, we (1) report the seasonality of fluxes of latent heat (LE), sensible heat (H), and outgoing short and longwave radiation at four diverse tropical forest sites across Amazonia—along the equator from the Caxiuanã and Tapajós National Forests in the eastern Amazon to a forest near Manaus, and from the equatorial zone to the southern forest in Reserva Jaru; (2) investigate how vegetation and climate influence these fluxes; and (3) evaluate land surface model performance by comparing simulations to observations. We found that previously identified failure of models to capture observed dry-season increases in evapotranspiration (ET) was associated with model overestimations of (1) magnitude and seasonality of Bowen ratios (relative to aseasonal observations in which sensible was only 20%–30% of the latent heat flux) indicating model exaggerated water limitation, (2) canopy emissivity and reflectance (albedo was only 10%–15% of incoming solar radiation, compared to 0.15%–0.22% simulated), and (3) vegetation temperatures (due to underestimation of dry-season ET and associated cooling). These partially compensating model-observation discrepancies (e.g., higher temperatures expected from excess Bowen ratios were partially ameliorated by brighter leaves and more interception/evaporation) significantly biased seasonal model estimates of net radiation (Rn), the key driver of water and energy fluxes (LE ~ 0.6 Rn and H ~ 0.15 Rn), though these biases varied among sites and models. A better representation of energy-related parameters associated with dynamic phenology (e.g., leaf optical properties, canopy interception, and skin temperature) could improve simulations and benchmarking of current vegetation–atmosphere exchange and reduce uncertainty of regional and global biogeochemical models

The Ionized Gas and Nuclear Environment in NGC 3783. I. Time-Averaged 900 ks Chandra Grating Spectroscopy

We present results from a 900 ks exposure of NGC 3783 with the High-Energy Transmission Grating Spectrometer on board the Chandra X-ray Observatory. The resulting X-ray spectrum has the best combination of signal-to-noise and resolution ever obtained for an AGN. This spectrum reveals absorption lines from H-like and He-like ions of N, O, Ne, Mg, Al, Si, and S. There are also possible absorption lines from H-like and He-like Ar and Ca. We also identify inner-shell absorption from lower-ionization ions such as Si_VII-Si_XII and S_XII-S_XIV. The iron absorption spectrum is very rich; L-shell lines of Fe_XVII-Fe_XXIV are detected, strong complex of M-shell lines, and probable resonance lines from Fe_XXV. The absorption lines are blueshifted relative to the systemic velocity by a mean velocity of -590+-150 km/s. We resolve many of the absorption lines, and their mean FWHM is 820+-280 km/s. We do not find correlations between the velocity shifts or the FWHMs with the ionization potentials of the ions. Most absorption lines show asymmetry, having more extended blue wings than red wings. In O_VII we have resolved this asymmetry to be from an additional absorption system at ~ -1300 km/s. The two X-ray absorption systems are consistent in velocity shift and FWHM with the ones identified in the UV lines of C IV, N V, and H I. Equivalent width measurements for all lines are given and column densities are calculated for several ions. We resolve the narrow Fe_K\alpha line at 6398.2+-3.3 eV to have a FWHM of 1720+-360 km/s, which suggests that this narrow line may be emitted from the outer part of the broad line region or the inner part of the torus. We also detect a `Compton shoulder' redward of the narrow Fe_K\alpha line which indicates that it arises in cold, Compton-thick gas.Comment: 19 pages, 12 figures (2 in color), emulateapj5, accepted for publication in The Astrophysical Journal Supplement