Laboratory Directed Research and Development Annual Report - Fiscal Year 2000

The projects described in this report represent the Laboratory's investment in its future and are vital to maintaining the ability to develop creative solutions for the scientific and technical challenges faced by DOE and the nation. In accordance with DOE guidelines, the report provides, a) a director's statement, b) an overview of the laboratory's LDRD program, including PNNL's management process and a self-assessment of the program, c) a five-year project funding table, and d) project summaries for each LDRD project

Determination of the Cosmic Distance Scale from Sunyaev-Zel'dovich Effect and Chandra X-ray Measurements of High Redshift Galaxy Clusters

We determine the distance to 38 clusters of galaxies in the redshift range 0.14 < z < 0.89 using X-ray data from Chandra and Sunyaev-Zeldovich Effect data from the Owens Valley Radio Observatory and the Berkeley-Illinois-Maryland Association interferometric arrays. The cluster plasma and dark matter distributions are analyzed using a hydrostatic equilibrium model that accounts for radial variations in density, temperature and abundance, and the statistical and systematic errors of this method are quantified. The analysis is performed via a Markov chain Monte Carlo technique that provides simultaneous estimation of all model parameters. We measure a Hubble constant of 76.9 +3.9-3.4 +10.0-8.0 km/s/Mpc (statistical followed by systematic uncertainty at 68% confidence) for an Omega_M=0.3, Omega_Lambda=0.7 cosmology. We also analyze the data using an isothermal beta model that does not invoke the hydrostatic equilibrium assumption, and find H_0=73.7 +4.6-3.8 +9.5-7.6 km/s/Mpc; to avoid effects from cool cores in clusters, we repeated this analysis excluding the central 100 kpc from the X-ray data, and find H_0=77.6 +4.8-4.3 +10.1-8.2 km/s/Mpc. The consistency between the models illustrates the relative insensitivity of SZE/X-ray determinations of H_0 to the details of the cluster model. Our determination of the Hubble parameter in the distant universe agrees with the recent measurement from the Hubble Space Telescope key project that probes the nearby universe.Comment: ApJ submitted (revised version

X-ray and Sunyaev-Zel'dovich Effect Measurements of the Gas Mass Fraction in Galaxy Clusters

We present gas mass fractions of 38 massive galaxy clusters spanning redshifts from 0.14 to 0.89, derived from Chandra X-ray data and OVRO/BIMA interferometric Sunyaev-Zel'dovich Effect measurements. We use three models for the gas distribution: (1) an isothermal beta-model fit jointly to the X-ray data at radii beyond 100 kpc and to all of the SZE data,(2) a non-isothermal double beta-model fit jointly to all of the X-ray and SZE data, and (3) an isothermal beta-model fit only to the SZE spatial data. We show that the simple isothermal model well characterizes the intracluster medium (ICM) outside of the cluster core in clusters with a wide range of morphological properties. The X-ray and SZE determinations of mean gas mass fractions for the 100 kpc-cut isothermal beta-model are fgas(X-ray)=0.110 +0.003-0.003 +0.006-0.018 and fgas(SZE)=0.116 +0.005-0.005 +0.009-0.026, where uncertainties are statistical followed by systematic at 68% confidence. For the non-isothermal double beta-model, fgas(X-ray)=0.119 +0.003-0.003 +0.007-0.014 and fgas(SZE)=0.121 +0.005-0.005 +0.009-0.016. For the SZE-only model, fgas(SZE)=0.120 +0.009-0.009 +0.009-0.027. Our results indicate that the ratio of the gas mass fraction within r2500 to the cosmic baryon fraction is 0.68 +0.10-0.16 where the range includes statistical and systematic uncertainties. By assuming that cluster gas mass fractions are independent of redshift, we find that the results are in agreement with standard LambdaCDM cosmology and are inconsistent with a flat matter dominated universe.Comment: ApJ, submitted. 47 pages, 5 figures, 8 table

Identification of disease causing loci using an array-based genotyping approach on pooled DNA

BACKGROUND: Pooling genomic DNA samples within clinical classes of disease followed by genotyping on whole-genome SNP microarrays, allows for rapid and inexpensive genome-wide association studies. Key to the success of these studies is the accuracy of the allelic frequency calculations, the ability to identify false-positives arising from assay variability and the ability to better resolve association signals through analysis of neighbouring SNPs. RESULTS: We report the accuracy of allelic frequency measurements on pooled genomic DNA samples by comparing these measurements to the known allelic frequencies as determined by individual genotyping. We describe modifications to the calculation of k-correction factors from relative allele signal (RAS) values that remove biases and result in more accurate allelic frequency predictions. Our results show that the least accurate SNPs, those most likely to give false-positives in an association study, are identifiable by comparing their frequencies to both those from a known database of individual genotypes and those of the pooled replicates. In a disease with a previously identified genetic mutation, we demonstrate that one can identify the disease locus through the comparison of the predicted allelic frequencies in case and control pools. Furthermore, we demonstrate improved resolution of association signals using the mean of individual test-statistics for consecutive SNPs windowed across the genome. A database of k-correction factors for predicting allelic frequencies for each SNP, derived from several thousand individually genotyped samples, is provided. Lastly, a Perl script for calculating RAS values for the Affymetrix platform is provided. CONCLUSION: Our results illustrate that pooling of DNA samples is an effective initial strategy to identify a genetic locus. However, it is important to eliminate inaccurate SNPs prior to analysis by comparing them to a database of individually genotyped samples as well as by comparing them to replicates of the pool. Lastly, detection of association signals can be improved by incorporating data from neighbouring SNPs

Sunyaev-Zel'dovich Effect Imaging of Massive Clusters of Galaxies at Redshift z > 0.8

We present Sunyaev-Zel'dovich Effect (SZE) imaging observations of three distant (z > 0.8) and highly X-ray luminous clusters of galaxies, Cl1226+33, Cl0152-13 and MS1054-03. Two of the clusters, Cl1226+33 and Cl0152-13, were recently discovered in deep ROSAT x-ray images. Their high X-ray luminosity suggests that they are massive systems which, if confirmed, would provide strong constraints on the cosmological parameters of structure formation models. Our Sunyaev-Zel'dovich Effect data provide confirmation that they are massive clusters similar to the well studied cluster MS1054-03. Assuming the clusters have the same gas mass fraction as that derived from SZE measurements of eighteen known massive clusters, we are able to infer their mass and electron temperature from the SZE data. The derived electron temperatures are 9.8, 8.7, and 10.4 keV, respectively, and we infer total masses of ~2 x 10^14 h^-1 Msun within a radius of 65 arcsec (340 h^{-1} kpc) for all three clusters. For Cl0152-13 and MS1054-03 we find good agreement between our SZE derived temperatures and those inferred from X-ray spectroscopy. No X-ray derived temperatures are available for Cl1226+33, and thus the SZE data provide the first confirmation that it is indeed a massive system. The demonstrated ability to determine cluster temperatures and masses from SZE observations without access to X-ray data illustrates the power of using deep SZE surveys to probe the distant universe.Comment: 9 pages, 1 figure, accepted for publication in ApJ Letter

Galaxy Cluster Gas Mass Fractions from Sunyaev-Zel'dovich Effect Measurements: Constraints on Omega_M

Using sensitive centimeter-wave receivers mounted on the Owens Valley Radio Observatory and Berkeley-Illinois-Maryland-Association millimeter arrays, we have obtained interferometric measurements of the Sunyaev-Zel'dovich (SZ) effect toward massive galaxy clusters. We use the SZ data to determine the pressure distribution of the cluster gas and, in combination with published X-ray temperatures, to infer the gas mass and total gravitational mass of 18 clusters. The gas mass fraction, f_g, is calculated for each cluster, and is extrapolated to the fiducial radius r_{500} using the results of numerical simulations. The mean f_g within r_{500} is 0.081+0.009 -0.011/(h_{100} (statistical uncertainty at 68% confidence level, assuming OmegaM=0.3, OmegaL=0.7). We discuss possible sources of systematic errors in the mean f_g measurement. We derive an upper limit for OmegaM from this sample under the assumption that the mass composition of clusters within r_{500} reflects the universal mass composition: Omega_M h < Omega_B/f_g. The gas mass fractions depend on cosmology through the angular diameter distance and the r_{500} correction factors. For a flat universe (OmegaL = 1 - OmegaM) and h=0.7, we find the measured gas mass fractions are consistent with Omegam less than 0.40, at 68% confidence. Including estimates of the baryons contained in galaxies and the baryons which failed to become bound during the cluster formation process, we find OmegaM \~0.25.Comment: 20 pages, 4 figures (1 color), submitted to Astrophysical Journal Uses emulateapj5.st

K2-288Bb: A Small Temperate Planet in a Low-mass Binary System Discovered by Citizen Scientists

Original content from this work may be used under the terms of the Creative Commons Attribution 3.0 licence. Any further distribution of this work must maintain attribution to the author(s) and the title of the work, journal citation and DOI.Observations from the Kepler and K2 missions have provided the astronomical community with unprecedented amounts of data to search for transiting exoplanets and other astrophysical phenomena. Here, we present K2-288, a low-mass binary system (M2.0 ± 1.0; M3.0 ± 1.0) hosting a small (R p = 1.9 R ⊕), temperate (T eq = 226 K) planet observed in K2 Campaign 4. The candidate was first identified by citizen scientists using Exoplanet Explorers hosted on the Zooniverse platform. Follow-up observations and detailed analyses validate the planet and indicate that it likely orbits the secondary star on a 31.39-day period. This orbit places K2-288Bb in or near the habitable zone of its low-mass host star. K2-288Bb resides in a system with a unique architecture, as it orbits at >0.1 au from one component in a moderate separation binary (a proj ~ 55 au), and further follow-up may provide insight into its formation and evolution. Additionally, its estimated size straddles the observed gap in the planet radius distribution. Planets of this size occur less frequently and may be in a transient phase of radius evolution. K2-288 is the third transiting planet system identified by the Exoplanet Explorers program and its discovery exemplifies the value of citizen science in the era of Kepler, K2, and the Transiting Exoplanet Survey Satellite

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

Iatrogenic air embolism: pathoanatomy, thromboinflammation, endotheliopathy, and therapies

Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition