Ionizing Radiation from Ex Vivo Sterilization Diminishes Fatigue but Not Static Murine Vertebral Body Mechanics

For a variety of medical and scientific reasons, human bones can be exposed to ionizing radiation. At relatively high doses (30,0005,000 Gy), ex vivo ionizing radiation is commonly used to sterilize bone allografts. However, ionizing radiation in these applications has been shown to increase risk of fracture clinically and decrease bone quality. Previously, we observed a significant decrease in compressive static strength and fatigue life of ex vivo whole bones exposed to x-ray radiation at 17,000 Gy and above; no changes in compressive mechanical properties were observed for radiation doses of 1,000 Gy and below. The gap in doses between no mechanical change (1,000 Gy) and significant mechanical degradation (17,000 Gy) is large, and it is unclear at what dose mechanical integrity begins to diminish in whole bones, and if its effects differ in response to static versus cyclic mechanical loading. This is a major clinical concern, as trabecular and cortical bone allografts are commonly used in structural, load-bearing applications. To gain insight into the effect of ionizing radiation from 1,000-17,000 Gy, we conducted an ex vivo radiation study on the static and fatigue mechanical properties of the vertebral whole bone. Our objectives were to: (1) quantify the effect of exposure to ex vivo ionizing radiation on the mechanical integrity (compressive static and fatigue) of whole bones; and (2) evaluate, if there are observed differences in mechanics, if they differ in magnitude for static versus cyclic properties. The results of this study will give insight into the need for changes in protocols for bone allograft radiation sterilization procedures

Integrable Deformations of c^=1\hat{c}=1 Strings in Flux Backgrounds

We study d=2 0A string theory perturbed by tachyon momentum modes in backgrounds with non-trivial tachyon condensate and Ramond-Ramond (RR) flux. In the matrix model description, we uncover a complexified Toda lattice hierarchy constrained by a pair of novel holomorphic string equations. We solve these constraints in the classical limit for general RR flux and tachyon condensate. Due to the non-holomorphic nature of the tachyon perturbations, the transcendental equations which we derive for the string susceptibility are manifestly non-holomorphic. We explore the phase structure and critical behavior of the theory.Comment: 39 pages, 4 figure

Ionizing Radiation from Ex Vivo Sterilization Diminishes Collagen Integrity and Vertebral Body Mechanics

Clinical exposure to ionizing radiation could put cancer radiotherapy or bone allograft patients at an increased risk of fracture. In these applications, ionizing radiation levels can range from accumulative 50 Gy for radiotherapy cancer treatment, to acute 35,000 Gy for allograft sterilization. Ionizing radiation has been shown to decrease bon equality through reduced strength and post-yield properties and degrade collagen integrity through either increased crosslinks (advanced glycation end products, AGEs)or fragmentation. It is unclear which collagen structural change accounts for reduced strength. The dose-dependent effect of ionizing radiation on mechanical and biochemical properties of whole bones are not well understood, particularly for ex vivo doses ranging from 50 to 35,000 Gy

KL Estimation of the Power Spectrum Parameters from the Angular Distribution of Galaxies in Early SDSS Data

We present measurements of parameters of the 3-dimensional power spectrum of galaxy clustering from 222 square degrees of early imaging data in the Sloan Digital Sky Survey. The projected galaxy distribution on the sky is expanded over a set of Karhunen-Loeve eigenfunctions, which optimize the signal-to-noise ratio in our analysis. A maximum likelihood analysis is used to estimate parameters that set the shape and amplitude of the 3-dimensional power spectrum. Our best estimates are Gamma=0.188 +/- 0.04 and sigma_8L = 0.915 +/- 0.06 (statistical errors only), for a flat Universe with a cosmological constant. We demonstrate that our measurements contain signal from scales at or beyond the peak of the 3D power spectrum. We discuss how the results scale with systematic uncertainties, like the radial selection function. We find that the central values satisfy the analytically estimated scaling relation. We have also explored the effects of evolutionary corrections, various truncations of the KL basis, seeing, sample size and limiting magnitude. We find that the impact of most of these uncertainties stay within the 2-sigma uncertainties of our fiducial result.Comment: Fig 1 postscript problem correcte

The Angular Power Spectrum of Galaxies from Early SDSS Data

We compute the angular power spectrum C_l from 1.5 million galaxies in early SDSS data on large angular scales, l<600. The data set covers about 160 square degrees, with a characteristic depth of order 1 Gpc/h in the faintest (21<r<22) of our four magnitude bins. Cosmological interpretations of these results are presented in a companion paper by Dodelson et al (2001). The data in all four magnitude bins are consistent with a simple flat ``concordance'' model with nonlinear evolution and linear bias factors of order unity. Nonlinear evolution is particularly evident for the brightest galaxies. A series of tests suggest that systematic errors related to seeing, reddening, etc., are negligible, which bodes well for the sixtyfold larger sample that the SDSS is currently collecting. Uncorrelated error bars and well-behaved window functions make our measurements a convenient starting point for cosmological model fitting.Comment: Replaced to match accepted ApJ version (14 pages). Data, window functions etc available at http://www.hep.upenn.edu/~max/sdss.html or from [email protected]

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

The 3D Power Spectrum from Angular Clustering of Galaxies in Early SDSS Data

Early photometric data from the Sloan Digital Sky Survey (SDSS) contain angular positions for 1.5 million galaxies. In companion papers, the angular correlation function $w(\theta)$ and 2D power spectrum $C_l$ of these galaxies are presented. Here we invert Limber's equation to extract the 3D power spectrum from the angular results. We accomplish this using an estimate of $dn/dz$, the redshift distribution of galaxies in four different magnitude slices in the SDSS photometric catalog. The resulting 3D power spectrum estimates from $w(\theta)$ and $C_l$ agree with each other and with previous estimates over a range in wavenumbers $0.03 < k/{\rm h Mpc}^{-1} < 1$. The galaxies in the faintest magnitude bin (21 < \rstar < 22, which have median redshift $z_m=0.43$) are less clustered than the galaxies in the brightest magnitude bin (18 < \rstar < 19 with $z_m=0.17$), especially on scales where nonlinearities are important. The derived power spectrum agrees with that of Szalay et al. (2001) who go directly from the raw data to a parametric estimate of the power spectrum. The strongest constraints on the shape parameter $\Gamma$ come from the faintest galaxies (in the magnitude bin 21 < \rstar < 22), from which we infer $\Gamma = 0.14^{+0.11}_{-0.06}$ (95% C.L.).Comment: 25 pages, 19 figure