The Ultraviolet Attenuation Law in Backlit Spiral Galaxies

(Abridged) The effective extinction law (attenuation behavior) in galaxies in the emitted ultraviolet is well known only for actively star-forming objects and combines effects of the grain properties, fine structure in the dust distribution, and relative distributions of stars and dust. We use GALEX, XMM Optical Monitor, and HST data to explore the UV attenuation in the outer parts of spiral disks which are backlit by other UV-bright galaxies, starting with candidates provided by Galaxy Zoo participants. Our analysis incorporates galaxy symmetry, using non-overlapping regions of each galaxy to derive error estimates on the attenuation measurements. The entire sample has an attenuation law close to the Calzetti et al. (1994) form; the UV slope for the overall sample is substantially shallower than found by Wild et al. (2011), a reasonable match to the more distant galaxies in our sample but not to the weighted combination including NGC 2207. The nearby, bright spiral NGC 2207 alone gives accuracy almost equal to the rest of our sample, and its outer arms have a very low level of foreground starlight. This "grey" law can be produced from the distribution of dust alone, without a necessary contribution from differential escape of stars from dense clouds. The extrapolation needed to compare attenution between backlit galaxies at moderate redshifts, and local systems from SDSS data, is mild enough to allow use of galaxy overlaps to trace the cosmic history of dust. For NGC 2207, the covering factor of clouds with small optical attenuation becomes a dominant factor farther into the ultraviolet, which opens the possibility that widespread diffuse dust dominates over dust in star-forming regions deep into the ultraviolet. Comparison with published radiative-transfer models indicates that the role of dust clumping dominates over differences in grain populations, at this spatial resolution.Comment: In press, Astronomical Journa

Discovery of a Substrate Selectivity Switch in Tyrosine Ammonia-Lyase, a Member of the Aromatic Amino Acid Lyase Family

SummaryTyrosine ammonia-lyase (TAL) is a recently described member of the aromatic amino acid lyase family, which also includes phenylalanine (PAL) and histidine ammonia-lyases (HAL). TAL is highly selective for L-tyrosine, and synthesizes 4-coumaric acid as a protein cofactor or antibiotic precursor in microorganisms. In this report, we identify a single active site residue important for substrate selection in this enzyme family. Replacing the active site residue His89 with Phe in TAL completely switched its substrate selectivity from tyrosine to phenylalanine, thereby converting it into a highly active PAL. When a corresponding mutation was made in PAL, the enzyme lost PAL activity and gained TAL activity. The discovered substrate selectivity switch is a rare example of a complete alteration of substrate specificity by a single point mutation. We also show that the identity of the amino acid at the switch position can serve as a guide to predict substrate specificities of annotated aromatic amino acid lyases in genome sequences

The Sudden Death of the Nearest Quasar

Galaxy formation is significantly modulated by energy output from supermassive black holes at the centers of galaxies which grow in highly efficient luminous quasar phases. The timescale on which black holes transition into and out of such phases is, however, unknown. We present the first measurement of the shutdown timescale for an individual quasar using X-ray observations of the nearby galaxy IC 2497, which hosted a luminous quasar no more than 70,000 years ago that is still seen as a light echo in `Hanny's Voorwerp', but whose present-day radiative output is lower by at least 2 and more likely by over 4 orders of magnitude. This extremely rapid shutdown provides new insights into the physics of accretion in supermassive black holes, and may signal a transition of the accretion disk to a radiatively inefficient state.Comment: 4 pages, 2 figures. Astrophysical Journal Letters, in pres

Prevalence, Clinical Profile, and Significance of Left Ventricular Remodeling in the End-Stage Phase of Hypertrophic Cardiomyopathy

Background— End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. Methods and Results— Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients ≤40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3±3 years. Duration from onset of HCM symptoms to ES identification was considerable (14±10 years), but ES onset to death/transplantation was brief (2.7±2 years). ES occurred with similar frequency in patients with or without prior myectomy ( P =0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. Conclusions— ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation

Multiparametric MRI changes persist beyond recovery in concussed adolescent hockey players

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion. Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. Conclusions: Changes persisted well after players’ clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated

Piperaquine Pharmacokinetic and Pharmacodynamic Profiles in Healthy Volunteers of Papua New Guinea after Administration of Three-Monthly Doses of Dihydroartemisinin–Piperaquine

Mass drug administration (MDA) with monthly dihydroartemisinin-piperaquine (DHA-PQP) appears useful in malaria control and elimination strategies. Determining the relationship between consecutive piperaquine phosphate (PQP) exposure and its impact on QT interval prolongation is a key safety consideration for MDA campaigns

Mid-life Leukocyte Telomere Length and Dementia Risk: An Observational and Mendelian Randomization Study of 435,046 UK Biobank Participants

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer\u27s disease and Alzheimer\u27s disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90–0.96, p = 3.37 × 10−7). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies

Persistent post-concussion brain changes in adolescent hockey players

Changes continue to occur in a concussed brain even after standard clinical tests have returned to normal. Damage in the very long fibre tracks in the brain of concussed players can be detected up to three months after the concussion and after the individuals have been approved for return to athletics. It is also possible to detect ‘hyper-connectivity’ in the brain, suggesting the brain is still trying to compensate for the concussion.https://ir.lib.uwo.ca/brainscanresearchsummaries/1003/thumbnail.jp

The Integrated WRF/Urban Modeling System: Development, Evaluation, and Applications to Urban Environmental Problems

To bridge the gaps between traditional mesoscale modeling and microscale modeling, the National Center for Atmospheric Research (NCAR), in collaboration with other agencies and research groups, has developed an integrated urban modeling system coupled to the Weather Research and Forecasting (WRF) model as a community tool to address urban environmental issues. The core of this WRF/urban modeling system consists of: 1) three methods with different degrees of freedom to parameterize urban surface processes, ranging from a simple bulk parameterization to a sophisticated multi-layer urban canopy model with an indoor outdoor exchange sub-model that directly interacts with the atmospheric boundary layer, 2) coupling to fine-scale Computational Fluid Dynamic (CFD) Reynolds-averaged Navier–Stokes (RANS) and Large-Eddy Simulation (LES) models for Transport and Dispersion (T&D) applications, 3) procedures to incorporate high-resolution urban land-use, building morphology, and anthropogenic heating data using the National Urban Database and Access Portal Tool (NUDAPT), and 4) an urbanized high-resolution land-data assimilation system (u-HRLDAS). This paper provides an overview of this modeling system; addresses the daunting challenges of initializing the coupled WRF/urban model and of specifying the potentially vast number of parameters required to execute the WRF/urban model; explores the model sensitivity to these urban parameters; and evaluates the ability of WRF/urban to capture urban heat islands, complex boundary layer structures aloft, and urban plume T&D for several major metropolitan regions. Recent applications of this modeling system illustrate its promising utility, as a regional climate-modeling tool, to investigate impacts of future urbanization on regional meteorological conditions and on air quality under future climate change scenarios

Multiparametric MRI Changes Persist Beyond Recovery in Concussed Adolescent Hockey Players

Objective: To determine whether multiparametric MRI data can provide insight into the acute and long-lasting neuronal sequelae after a concussion in adolescent athletes. Methods: Players were recruited from Bantam hockey leagues in which body checking is first introduced (male, age 11–14 years). Clinical measures, diffusion metrics, resting-state network and region-to-region functional connectivity patterns, and magnetic resonance spectroscopy absolute metabolite concentrations were analyzed from an independent, age-matched control group of hockey players (n 5 26) and longitudinally in concussed athletes within 24 to 72 hours (n 5 17) and 3 months (n 5 14) after a diagnosed concussion. Results: There were diffusion abnormalities within multiple white matter tracts, functional hyperconnectivity, and decreases in choline 3 months after concussion. Tract-specific spatial statistics revealed a large region along the superior longitudinal fasciculus with the largest decreases in diffusivity measures, which significantly correlated with clinical deficits. This region also spatially intersected with probabilistic tracts connecting cortical regions where we found acute functional connectivity changes. Hyperconnectivity patterns at 3 months after concussion were present only in players with relatively less severe clinical outcomes, higher choline concentrations, and diffusivity indicative of relatively less axonal disruption. Conclusions: Changes persisted well after players’ clinical scores had returned to normal and they had been cleared to return to play. Ongoing white matter maturation may make adolescent athletes particularly vulnerable to brain injury, and they may require extended recovery periods. The consequences of early brain injury for ongoing brain development and risk of more serious conditions such as second impact syndrome or neural degenerative processes need to be elucidated