The Linear Theory Power Spectrum from the Lyman-alpha Forest in the Sloan Digital Sky Survey

We analyze the SDSS Ly-alpha forest P_F(k,z) measurement to determine the linear theory power spectrum. Our analysis is based on fully hydrodynamic simulations, extended using hydro-PM simulations. We account for the effect of absorbers with damping wings, which leads to an increase in the slope of the linear power spectrum. We break the degeneracy between the mean level of absorption and the linear power spectrum without significant use of external constraints. We infer linear theory power spectrum amplitude Delta^2_L(k_p=0.009s/km,z_p=3.0)=0.452_{-0.057-0.116}^{+0.069+0.141} and slope n_eff=-2.321_{-0.047-0.102}^{+0.055+0.131} (possible systematic errors are included through nuisance parameters in the fit - a factor >~5 smaller errors would be obtained on both parameters if we ignored modeling uncertainties). The errors are correlated and not perfectly Gaussian, so we provide a chi^2 table to accurately describe the results. The result corresponds to sigma_8=0.85, n=0.94, for a LCDM model with Omega_m=0.3, Omega_b=0.04, and h=0.7, but is most useful in a combined fit with the CMB. The inferred curvature of the linear power spectrum and the evolution of its amplitude and slope with redshift are consistent with expectations for LCDM models, with the evolution of the slope, in particular, being tightly constrained. We use this information to constrain systematic contamination, e.g., fluctuations in the UV background. This paper should serve as a starting point for more work to refine the analysis, including technical improvements such as increasing the size and number of the hydrodynamic simulations, and improvements in the treatment of the various forms of feedback from galaxies and quasars.Comment: Improved presentation, including fit results for (z). Simple code to produce LyaF chi^2 given linear power spectrum available at: http://www.cita.utoronto.ca/~pmcdonal/code.htm

Diagnosis, Prognosis, and Therapy of Transthyretin Amyloidosis

AbstractTransthyretin amyloidosis is a fatal disorder that is characterized primarily by progressive neuropathy and cardiomyopathy. It occurs in both a mutant form (with autosomal dominant inheritance) and a wild-type form (with predominant cardiac involvement). This article guides clinicians as to when the disease should be suspected, describes the appropriate diagnostic evaluation for those with known or suspected amyloidosis, and reviews the interventions currently available for affected patients

Efficacy and safety of vutrisiran for patients with hereditary transthyretin-mediated amyloidosis with polyneuropathy: a randomized clinical trial

BACKGROUND: The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary transthyretin (ATTRv) amyloidosis with polyneuropathy. METHODS: HELIOS-A was a phase 3, global, open-label study comparing the efficacy and safety of vutrisiran with an external placebo group (APOLLO study). Patients were randomized 3:1 to subcutaneous vutrisiran 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg every 3 weeks (Q3W) for 18 months. RESULTS: HELIOS-A enrolled 164 patients (vutrisiran, n = 122; patisiran reference group, n = 42); external placebo, n = 77. Vutrisiran met the primary endpoint of change from baseline in modified Neuropathy Impairment Score +7 (mNIS+7) at 9 months (p = 3.54 × 10−12), and all secondary efficacy endpoints; significant improvements versus external placebo were observed in Norfolk Quality of Life-Diabetic Neuropathy, 10-meter walk test (both at 9 and 18 months), mNIS+7, modified body-mass index, and Rasch-built Overall Disability Scale (all at 18 months). TTR reduction with vutrisiran Q3M was non-inferior to within-study patisiran Q3W. Most adverse events were mild or moderate in severity, and consistent with ATTRv amyloidosis natural history. There were no drug-related discontinuations or deaths. CONCLUSIONS: Vutrisiran significantly improved multiple disease-relevant outcomes for ATTRv amyloidosis versus external placebo, with an acceptable safety profile

Sloan Digital Sky Survey Multicolor Observations of GRB010222

The discovery of an optical counterpart to GRB010222 (detected by BeppoSAX; Piro 2001) was announced 4.4 hrs after the burst by Henden (2001a). The Sloan Digital Sky Survey's 0.5m photometric telescope (PT) and 2.5m survey telescope were used to observe the afterglow of GRB010222 starting 4.8 hours after the GRB. The 0.5m PT observed the afterglow in five, 300 sec g' band exposures over the course of half an hour, measuring a temporal decay rate in this short period of F_nu \propto t^{-1.0+/-0.5}. The 2.5m camera imaged the counterpart nearly simultaneously in five filters (u' g' r' i' z'), with r' = 18.74+/-0.02 at 12:10 UT. These multicolor observations, corrected for reddening and the afterglow's temporal decay, are well fit by the power-law F_nu \propto nu^{-0.90+/-0.03} with the exception of the u' band UV flux which is 20% below this slope. We examine possible interpretations of this spectral shape, including source extinction in a star forming region.Comment: 8 pages, 4 figures, accepted for publication in ApJ. Two figures added, minor changes to text in this draft. Related material can be found at: http://sdss.fnal.gov:8000/grb

Redshift Filtering by Swift Apparent X-ray Column Density

We remark on the utility of an observational relation between the absorption column density in excess of the Galactic absorption column density, $\Delta N_{\rm H} = N_{\rm H, fit} - N_{\rm H, gal}$, and redshift, z, determined from all 55 Swift-observed long bursts with spectroscopic redshifts as of 2006 December. The absorption column densities, $N_{\rm H, fit}$, are determined from powerlaw fits to the X-ray spectra with the absorption column density left as a free parameter. We find that higher excess absorption column densities with $\Delta N_{\rm H} > 2\times 10^{21}$ cm$^{-2}$ are only present in bursts with redshifts z$<$2. Low absorption column densities with $\Delta N_{\rm H} < 1\times 10^{21}$ cm$^{-2}$ appear preferentially in high-redshift bursts. Our interpretation is that this relation between redshift and excess column density is an observational effect resulting from the shift of the source rest-frame energy range below 1 keV out of the XRT observable energy range for high redshift bursts. We found a clear anti-correlation between $\Delta N_{\rm H}$ and z that can be used to estimate the range of the maximum redshift of an afterglow. A critical application of our finding is that rapid X-ray observations can be used to optimize the instrumentation used for ground-based optical/NIR follow-up observations. Ground-based spectroscopic redshift measurements of as many bursts as possible are crucial for GRB science.Comment: revised version including updates and the referee's comments, accepted for publication in the Astronomical Journal, 12 pages, 2 figures, 2 tables - v3 contains an update on the reference lis

SDSS 0956+5128: A Broad-line Quasar with Extreme Velocity Offsets

We report on the discovery of a Type 1 quasar, SDSS 0956+5128, with a surprising combination of extreme velocity offsets. SDSS 0956+5128 is a broad-lined quasar exhibiting emission lines at three substantially different redshifts: a systemic redshift of z ~ 0.714 based on narrow emission lines, a broad MgII emission line centered 1200 km/s bluer than the systemic velocity, at z ~ 0.707, and broad H\alpha and H\beta emission lines centered at z ~ 0.690. The Balmer line peaks are 4100 km/s bluer than the systemic redshift. There are no previously known objects with such an extreme difference between broad MgII and broad Balmer emission. The two most promising explanations are either an extreme disk emitter or a high-velocity black hole recoil. However, neither explanation appears able to explain all of the observed features of SDSS 0956+5128, so the object may provide a challenge to our general understanding of quasar physics.Comment: ApJ, accepte

GRB 060313: A New Paradigm for Short-Hard Bursts?

We report the simultaneous observations of the prompt emission in the gamma-ray and hard X-ray bands by the Swift-BAT and the KONUS-Wind instruments of the short-hard burst, GRB 060313. The observations reveal multiple peaks in both the gamma-ray and hard X-ray bands suggesting a highly variable outflow from the central explosion. We also describe the early-time observations of the X-ray and UV/Optical afterglows by the Swift XRT and UVOT instruments. The combination of the X-ray and UV/Optical observations provide the most comprehensive lightcurves to date of a short-hard burst at such an early epoch. The afterglows exhibit complex structure with different decay indices and flaring. This behavior can be explained by the combination of a structured jet, radiative loss of energy, and decreasing microphysics parameters occurring in a circum-burst medium with densities varying by a factor of approximately two on a length scale of 10^17 cm. These density variations are normally associated with the environment of a massive star and inhomogeneities in its windy medium. However, the mean density of the observed medium (n approximately 10^&#8722;4 cm^3) is much less than that expected for a massive star. Although the collapse of a massive star as the origin of GRB 060313 is unlikely, the merger of a compact binary also poses problems for explaining the behavior of this burst. Two possible suggestions for explaining this scenario are: some short bursts may arise from a mechanism that does not invoke the conventional compact binary model, or soft late-time central engine activity is producing UV/optical but no X-ray flaring.Comment: 28 pages, 6 figures. Accepted for publication in ApJ. Clarifications made and typos correcte

The Very Short Period M Dwarf Binary SDSS J001641-000925

We present follow-up observations and analysis of the recently discovered short period low-mass eclipsing binary, SDSS J001641-000925. With an orbital period of 0.19856 days, this system has one of the shortest known periods for an M dwarf binary system. Medium-resolution spectroscopy and multi-band photometry for the system are presented. Markov chain Monte Carlo modeling of the light curves and radial velocities yields estimated masses for the stars of M1 = 0.54 +/- 0.07 Msun and M2 = 0.34 +/- 0.04 Msun, and radii of R1 = 0.68 +/- 0.03 Rsun and R2 = 0.58 +/- 0.03 Rsun respectively. This solution places both components above the critical Roche overfill limit, providing strong evidence that SDSS J001641-000925 is the first verified M-dwarf contact binary system. Within the follow-up spectroscopy we find signatures of non-solid body rotation velocities, which we interpret as evidence for mass transfer or loss within the system. In addition, our photometry samples the system over 9 years, and we find strong evidence for period decay at the rate of dP/dt ~8 s/yr. Both of these signatures raise the intriguing possibility that the system is in over-contact, and actively losing angular momentum, likely through mass loss. This places SDSS J001641-000925 as not just the first M-dwarf over-contact binary, but one of the few systems of any spectral type known to be actively undergoing coalescence. Further study SDSS J001641-000925 is on-going to verify the nature of the system, which may prove to be a unique astrophysical laboratory.Comment: 11 figures, ApJ Accepte

Liver Directed Drugs for Transthyretin-Mediated Amyloidosis

AIM: Transthyretin-mediated amyloidosis (ATTR) is a rare, under-recognized, progressively debilitating, fatal disease caused by the aggregation and extracellular deposition of amyloid transthyretin (TTR) fibrils in multiple organs and tissues throughout the body. TTR is predominantly synthesized by the liver, and normally circulates as a homotetramer, while misfolded monomers aggregate to form amyloid fibrils. One strategy to treat ATTR amyloidosis is to reduce the amount of TTR produced by the liver using drugs that directly target the TTR mRNA or gene. METHODS: This narrative review focuses on how TTR gene silencing tools act to reduce TTR production, describing strategies for improved targeted delivery of these agents to hepatocytes where TTR is preferentially expressed. RESULTS: Antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs), termed RNA silencers, cause selective degradation of TTR mRNA, while a TTR gene editing tool reduces TTR expression by introducing nonsense mutations into the TTR gene. Two strategies to facilitate tissue-specific delivery of these nucleic acid-based drugs employ endogenous receptors expressed by hepatocytes. Lipid nanoparticles (LNPs) that recruit apolipoprotein E support low density lipoprotein receptor-mediated uptake of unconjugated siRNA and is now used for CRISPR gene editing tools. Additionally, conjugating N-acetylgalactosamine (GalNAc) moieties to ASOs or siRNAs facilitates receptor-mediated uptake by the asialoglycoprotein receptor. CONCLUSION: ATTR is a progressive disease with various clinical manifestations due to TTR aggregation, deposition, and amyloid formation. Receptor-targeted ligands (e.g., GalNAc) and nanoparticle encapsulation (e.g., LNPs) are technologies to deliver ASOs, siRNAs, and gene editing tools to hepatocytes, the primary location of TTR synthesis