A Tale of Two Trials: The Impact of 5α-Reductase Inhibition on Prostate Cancer (Review)

The use of 5α-reductase inhibitors (5α-RIs) as prostate cancer chemoprevention agents is controversial. Two large randomized trials, the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial, have both shown a decreased incidence of prostate cancer in patients administered with 5α-RIs. Both studies showed, however, an increased risk of higher-grade prostate cancer. Numerous studies have since analyzed the inherent biases in these landmark studies and have used mathematical modeling to estimate the true incidence of prostate cancer and the risk for high-grade prostate cancer in patients undergoing 5α-RI treatment. All primary publications associated with the PCPT and REDUCE studies were reviewed in detail. Pertinent references from the above publications were assessed and a literature search of all published articles associated with PCPT, REDUCE or 5α-RIs as chemopreventative agents through October 2013 was performed using Pubmed/Medline. PCPT and REDUCE both showed a significant decrease in the incidence of prostate cancer following the administration of 5α-reductase inhibitor, as compared with placebo, suggesting that 5α-RIs may be effective agents for prostate cancer chemoprevention. Inherent biases in the design of these two studies may have caused an artificial increase in the number of high-grade cancers reported. Mathematical models, that integrated data from these trials, revealed neither an increased nor decreased risk of high-grade disease when taking these biases into consideration. Moderately strong evidence exists that 5α-RIs may reduce the risk of prostate cancer. PCPT and REDUCE showed a decreased prevalence of prostate cancer in patients taking 5α-RIs. Urologists should have a working knowledge of these studies and discuss with patients the risks and benefits of 5α-RI treatment. Further studies to evaluate the cost-effectiveness of chemoprevention with 5α-RIs and appropriate patient selection are warranted

Detection of water vapor in the terrestrial planet forming region of a transition disk

We report a detection of water vapor in the protoplanetary disk around DoAr 44 with the Texas Echelon Cross Echelle Spectrograph --- a visitor instrument on the Gemini north telescope. The DoAr 44 disk consists of an optically thick inner ring and outer disk, separated by a dust-cleared 36 AU gap, and has therefore been termed "pre-transitional". To date, this is the only disk with a large inner gap known to harbor detectable quantities of warm (T=450 K) water vapor. In this work, we detect and spectrally resolve three mid-infrared pure rotational emission lines of water vapor from this source, and use the shapes of the emission lines to constrain the location of the water vapor. We find that the emission originates near 0.3 AU --- the inner disk region. This characteristic region coincides with that inferred for both optically thick and thin thermal infrared dust emission, as well as rovibrational CO emission. The presence of water in the dust-depleted region implies substantial columns of hydrogen (>10^{22} cm-2) as the water vapor would otherwise be destroyed by photodissociation. Combined with the dust modeling, this column implies a gas/small-dust ratio in the optically thin dusty region of >1000. These results demonstrate that DoAr 44 has maintained similar physical and chemical conditions to classical protoplanetary disks in its terrestrial-planet forming regions, in spite of having formed a large gap.Comment: Paper accepted to the Astrophysical Journal Letter

Anthrax Toxin Receptor 2 Determinants that Dictate the pH Threshold of Toxin Pore Formation

The anthrax toxin receptors, ANTXR1 and ANTXR2, act as molecular clamps to prevent the protective antigen (PA) toxin subunit from forming pores until exposure to low pH. PA forms pores at pH ∼6.0 or below when it is bound to ANTXR1, but only at pH ∼5.0 or below when it is bound to ANTXR2. Here, structure-based mutagenesis was used to identify non-conserved ANTXR2 residues responsible for this striking 1.0 pH unit difference in pH threshold. Residues conserved between ANTXR2 and ANTXR1 that influence the ANTXR2-associated pH threshold of pore formation were also identified. All of these residues contact either PA domain 2 or the neighboring edge of PA domain 4. These results provide genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation

Waterbird monitoring and habitat association modeling to inform tidal marsh restoration in an urbanized estuary

The San Francisco Bay (SFB), like many other urbanized estuaries, is a critical wintering and stop-over area for migratory waterbirds. More than a million wintering waterbirds annually rely on a mosaic of natural and managed habitats in SFB, including former salt ponds. The South Bay Salt Pond Restoration Project plans restore 50 to 90% of a 6,100 hectare former salt production pond complex to tidal marsh, while maintaining the rest as foraging and roosting areas for migratory birds. Since 2002, we have evaluated migratory waterbird use of pre- and post-restoration salt ponds in south SFB. Our approach has been to use monthly surveys, applied studies and modeling to evaluate avian response to this changing habitat. Trend analyses indicate that overall waterbird numbers have nearly doubled across the complex from 2003-2014. Dabbling ducks increased significantly during initial phases of the project, while diving ducks, small and medium shorebird abundances declined initially, but rebounded in recent years. We modeled relationships between abundances of multiple species and habitat characteristics at both landscape and micro-scales. Modeling results suggest that the importance of different habitat characteristics varies among waterbird guilds. For example, foraging diving duck abundances were higher in deep, un-breached ponds, located close to the edge of SFB, while foraging small shorebirds predominated in shallow, breached ponds containing islands. Our research highlights important habitat characteristics both within and across wetland areas, and provides a unique opportunity to guide future management and restoration decisions for multiple species across large landscapes in SFB and other urbanized estuaries

Looking for Pure Rotational H_2 Emission from Protoplanetary Disks

We report on a limited search for pure-rotational molecular hydrogen emission associated with young, pre-main-sequence stars. We looked for H_2 v=0 J = 3->1 and J = 4->2 emission in the mid-infrared using the Texas Echelon-Cross-Echelle Spectrograph (TEXES) at NASA's 3m Infrared Telescope Facility. The high spectral and spatial resolution of our observations lead to more stringent limits on narrow line emission close to the source than previously achieved. One star, AB Aur, shows a possible (2sigma) H_2 detection, but further observations are required to make a confident statement. Our non-detections suggest that a significant fraction, perhaps all, of previously reported H_2 emission towards these objects could be extended on scales of 5" or more.Comment: 14 pages including 2 figures. Accepted by ApJ Letter

A Multiscale Progressive Failure Modeling Methodology for Composites that Includes Fiber Strength Stochastics

A multiscale modeling methodology was developed for continuous fiber composites that incorporates a statistical distribution of fiber strengths into coupled multiscale micromechanics/finite element (FE) analyses. A modified two-parameter Weibull cumulative distribution function, which accounts for the effect of fiber length on the probability of failure, was used to characterize the statistical distribution of fiber strengths. A parametric study using the NASA Micromechanics Analysis Code with the Generalized Method of Cells (MAC/GMC) was performed to assess the effect of variable fiber strengths on local composite failure within a repeating unit cell (RUC) and subsequent global failure. The NASA code FEAMAC and the ABAQUS finite element solver were used to analyze the progressive failure of a unidirectional SCS-6/TIMETAL 21S metal matrix composite tensile dogbone specimen at 650 degC. Multiscale progressive failure analyses were performed to quantify the effect of spatially varying fiber strengths on the RUC-averaged and global stress-strain responses and failure. The ultimate composite strengths and distribution of failure locations (predominately within the gage section) reasonably matched the experimentally observed failure behavior. The predicted composite failure behavior suggests that use of macroscale models that exploit global geometric symmetries are inappropriate for cases where the actual distribution of local fiber strengths displays no such symmetries. This issue has not received much attention in the literature. Moreover, the model discretization at a specific length scale can have a profound effect on the computational costs associated with multiscale simulations.models that yield accurate yet tractable results

Anthrax Toxin Receptor 2–Dependent Lethal Toxin Killing In Vivo

Anthrax toxin receptors 1 and 2 (ANTXR1 and ANTXR2) have a related integrin-like inserted (I) domain which interacts with a metal cation that is coordinated by residue D683 of the protective antigen (PA) subunit of anthrax toxin. The receptor-bound metal ion and PA residue D683 are critical for ANTXR1-PA binding. Since PA can bind to ANTXR2 with reduced affinity in the absence of metal ions, we reasoned that D683 mutant forms of PA might specifically interact with ANTXR2. We show here that this is the case. The differential ability of ANTXR1 and ANTXR2 to bind D683 mutant PA proteins was mapped to nonconserved receptor residues at the binding interface with PA domain 2. Moreover, a D683K mutant form of PA that bound specifically to human and rat ANTXR2 mediated killing of rats by anthrax lethal toxin, providing strong evidence for the physiological importance of ANTXR2 in anthrax disease pathogenesis

Accurate Wavenumbers for Mid-Infrared Fine-Structure Lines

We present accurate new wavenumbers for a set of 13 mid-infrared fine-structure lines. The wavenumbers were determined from observations of the planetary nebula NGC 7027 and of the red supergiant Alpha Scorpii. Most of the new wavenumbers are good to within 0.0025%, or 8 km/s. We provide details on the measurements and present an analysis of the errors. In addition, we present the first observations of hyperfine splitting in the [Na IV] 1106 cm-1 line.Comment: 12 pages text, 2 postscript figures, uses AASTeX macros, figures are gzipped and uuencode

A Candidate Dual QSO at Cosmic Noon

We report the discovery of a candidate dual QSO at z=1.889, a redshift that is in the era known as "cosmic noon" where most of the Universe's black hole and stellar mass growth occurred. The source was identified in Hubble Space Telescope WFC3/IR images of a dust-reddened QSO that showed two closely-separated point sources at a projected distance of 0.26", or 2.2 kpc. This red QSO was targeted for imaging to explore whether red QSOs are hosted by merging galaxies. We subsequently obtained a spatially-resolved STIS spectrum of the system, covering the visible spectral range, and verifying the presence of two distinct QSO components. We also obtained high-resolution radio continuum observations with the VLBA at 1.4 GHz (21-cm L band) and found two sources coincident with the optical positions. The sources have similar black hole masses, bolometric luminosities, and radio loudness parameters. However, their colors and reddenings differ significantly. The redder QSO has a higher Eddington ratio, consistent with previous findings. We consider the possibility of gravitational lensing and and find that it would require extreme and unlikely conditions. If confirmed as a bona-fide dual QSO, this system would link dust-reddening to galaxy and supermassive black hole mergers, opening up a new population in which to search for samples of dual AGN.Comment: Accepted for publication in ApJ Letter

The Spitzer High Redshift Radio Galaxy Survey

We present results from a comprehensive imaging survey of 70 radio galaxies at redshifts 1<z<5.2 using all three cameras onboard the Spitzer Space Telescope. The resulting spectral energy distributions unambiguously show a stellar population in 46 sources and hot dust emission associated with the active nucleus in 59. Using a new restframe S_3um/S_1.6um versus S_um/S_3um criterion, we identify 42 sources where the restframe 1.6um emission from the stellar population can be measured. For these radio galaxies, the median stellar mass is high, 2x10^11 M_sun, and remarkably constant within the range 13, there is tentative evidence for a factor of two decrease in stellar mass. This suggests that radio galaxies have assembled the bulk of their stellar mass by z~3, but confirmation by more detailed decomposition of stellar and AGN emission is needed. The restframe 500 MHz radio luminosities are only marginally correlated with stellar mass but are strongly correlated with the restframe 5um hot dust luminosity. This suggests that the radio galaxies have a large range of Eddington ratios. We also present new Very Large Array 4.86 and 8.46 GHz imaging of 14 radio galaxies and find that radio core dominance --- an indicator of jet orientation --- is strongly correlated with hot dust luminosity. While all of our targets were selected as narrow-lined, type 2 AGNs, this result can be understood in the context of orientation-dependent models if there is a continuous distribution of orientations from obscured type 2 to unobscured type 1 AGNs rather than a clear dichotomy. Finally, four radio galaxies have nearby (<6") companions whose mid-IR colors are suggestive of their being AGNs. This may indicate an association between radio galaxy activity and major mergers.Comment: 31 pages, 125 figures. Accepted for publication in the Astrophysical Journa