NICMOS and VLA Observations of the Gravitatonally Lensed Ultraluminous BAL Quasar APM~08279+5255: Detection of a Third Image

We present a suite of observations of the recently identified ultraluminous BAL quasar APM 08279+5255, taken both in the infra-red with the NICMOS high resolution camera on board the Hubble Space Telescope, and at 3.5cm with the Very Large Array. With an inferred luminosity of ~5x10^15 Solar luminosities, APM 08279+5255 is apparently the most luminous system known. Extant ground-based images show that APM 08279+5255 is not point-like, but is instead separated into two components, indicative of gravitational lensing. The much higher resolution images presented here also reveal two point sources, A and B, of almost equal brightness (f_B/f_A=0.782 +/- 0.010), separated by 0."378 +/- 0."001, as well as a third, previously unknown, fainter image, C, seen between the brighter images. While the nature of C is not fully determined, several lines of evidence point to it being a third gravitationally lensed image of the quasar, rather than being the lensing galaxy. Simple models which recover the relative image configuration and brightnesses are presented. While proving to be substantially amplified, APM 08279+5255 possesses an intrinsic bolometric luminosity of ~10^14 to 10^15 Solar luminosities and remains amongst the most luminous objects known.Comment: 21 pages, 5 figures (2 as GIF files); accepted for publication in the Astronomical Journa

Submillimeter Observations of the Ultraluminous BAL Quasar APM 08279+5255

With an inferred bolometric luminosity of 5\times10^{15}{\rm \lsun}, the recently identified z=3.87, broad absorption line quasar APM 08279+5255 is apparently the most luminous object currently known. As half of its prodigious emission occurs in the infrared, APM 08279+5255 also represents the most extreme example of an Ultraluminous Infrared Galaxy. Here, we present new submillimeter observations of this phenomenal object; while indicating that a vast quantity of dust is present, these data prove to be incompatible with current models of emission mechanisms and reprocessing in ultraluminous systems. The influence of gravitational lensing upon these models is considered and we find that while the emission from the central continuum emitting region may be significantly enhanced, lensing induced magnification cannot easily reconcile the models with observations. We conclude that further modeling, including the effects of any differential magnification is required to explain the observed emission from APM 08279+5255.Comment: 12 Pages with Two figures. Accepted for publication in the Astrophysical Journal Letter

APM 08279+5255: an ultraluminous BAL quasar at a redshift z=3.87

We report on the discovery of a highly luminous, broad absorption line quasar at a redshift of $z=3.87$ which is positionally coincident, within one arcsecond, with the IRAS FSC source F08279+5255. A chance alignment of the quasar and the IRAS source is extremely unlikely and we argue that the optical and FIR flux are different manifestations of the same object. With an R-band magnitude of 15.2, and an IRAS 60\mum flux of 0.51\jy, APM 08279+5255 is (apparently) easily the most intrinsically luminous object known, with L_{Bol}\sim5\times10^{15}L_{\odot}}. Imaging suggests that gravitational lensing may play a role in amplifying the intrinsic properties of the system. The optical spectrum of the quasar clearly reveals the presence of three potential lensing galaxies, \mg absorption systems at $z=1.18$ and $z=1.81$, and a \ly absorption system at $z=3.07$. We estimate the total amplification of the optical component to be $\approx40$, but, due to the larger scale of the emitting region, would expect the infrared amplification to be significantly less. Even making the conservative assumption that all wavelengths are amplified by a factor 40, APM 08279+5255 still possesses a phenomenal luminosity of \simgt 10^{14L_{\odot}}, indicating that it belongs to a small, but significant population of high--redshift, hyperluminous objects with copious infrared emission.Comment: 15 Pages with Four figures. Accepted for publication in the Astrophysical Journa

Great Circle tidal streams: evidence for a nearly spherical massive dark halo around the Milky Way

An all high-latitude sky survey for cool carbon giant stars in the Galactic halo has revealed 75 such stars, of which the majority are new detections. Of these, more than half are clustered on a Great Circle on the sky which intersects the center of Sagittarius dwarf galaxy (Sgr) and is parallel to its proper motion vector, while many of the remainder are outlying Magellanic Cloud C-stars. A pole-count analysis of the carbon star distribution clearly indicates that the Great Circle stream we have isolated is statistically significant, being a 5-6 sigma over-density. These two arguments strongly support our conclusion that a large fraction of the Halo carbon stars originated in Sgr. The stream orbits the Galaxy between the present location of Sgr, 16 kpc from the Galactic center, and the most distant stream carbon star, at ~60 kpc. It follows neither a polar nor a Galactic plane orbit, so that a large range in both Galactic R and z distances are probed. That the stream is observed as a Great Circle indicates that the Galaxy does not exert a significant torque upon the stream, so the Galactic potential must be nearly spherical in the regions probed by the stream. We present N-body experiments simulating this disruption process as a function of the distribution of mass in the Galactic halo. A likelihood analysis shows that, in the Galactocentric distance range 16 kpc < R < 60 kpc, the dark halo is most likely almost spherical. We rule out, at high confidence levels, the possibility that the Halo is significantly oblate, with isodensity contours of aspect q_m < 0.7. This result is quite unexpected and contests currently popular galaxy formation models. (Abridged)Comment: 26 pages, 13 figures (6 in color, 8 chunky due to PS compression), minor revisions, accepted by Ap

Life Beyond the Solar System: Remotely Detectable Biosignatures

For the first time in human history, we will soon be able to apply to the scientific method to the question "Are We Alone?" The rapid advance of exoplanet discovery, planetary systems science, and telescope technology will soon allow scientists to search for life beyond our Solar System through direct observation of extrasolar planets. This endeavor will occur alongside searches for habitable environments and signs of life within our Solar System. While these searches are thematically related and will inform each other, they will require separate observational techniques. The search for life on exoplanets holds potential through the great diversity of worlds to be explored beyond our Solar System. However, there are also unique challenges related to the relatively limited data this search will obtain on any individual world

The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes

Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control the infection, but treatment is life-long and has high costs and unpredictable long-term side effects. The profound suppression of HBV by the nucleos(t)ide analogs and their ability to cure some patients indicates that they can push HBV to the brink of extinction. Consequently, more patients could be cured by suppressing HBV replication further using a new drug in combination with the nucleos(t)ide analogs. The HBV ribonuclease H (RNAseH) is a logical drug target because it is the second of only two viral enzymes that are essential for viral replication, but it has not been exploited, primarily because it is very difficult to produce active enzyme. To address this difficulty, we expressed HBV genotype D and H RNAseHs in E. coli and enriched the enzymes by nickel-affinity chromatography. HBV RNAseH activity in the enriched lysates was characterized in preparation for drug screening. Twenty-one candidate HBV RNAseH inhibitors were identified using chemical structure-activity analyses based on inhibitors of the HIV RNAseH and integrase. Twelve anti-RNAseH and anti-integrase compounds inhibited the HBV RNAseH at 10 μM, the best compounds had low micromolar IC50 values against the RNAseH, and one compound inhibited HBV replication in tissue culture at 10 μM. Recombinant HBV genotype D RNAseH was more sensitive to inhibition than genotype H. This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced. The high percentage of compounds developed against the HIV RNAseH and integrase that were active against the HBV RNAseH indicates that the extensive drug design efforts against these HIV enzymes can guide anti-HBV RNAseH drug discovery. Finally, differential inhibition of HBV genotype D and H RNAseHs indicates that viral genetic variability will be a factor during drug development. © 2013 Tavis et al

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society