Genome-Wide Association with Diabetes-Related Traits in the Framingham Heart Study

BACKGROUND: Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants. METHODS: We used the Affymetrix 100K SNP array in 1,087 Framingham Offspring Study family members to examine genetic associations with three diabetes-related quantitative glucose traits (fasting plasma glucose (FPG), hemoglobin A1c, 28-yr time-averaged FPG (tFPG)), three insulin traits (fasting insulin, HOMA-insulin resistance, and 0–120 min insulin sensitivity index); and with risk for diabetes. We used additive generalized estimating equations (GEE) and family-based association test (FBAT) models to test associations of SNP genotypes with sex-age-age2-adjusted residual trait values, and Cox survival models to test incident diabetes. RESULTS: We found 415 SNPs associated (at p 1%) 100K SNPs in LD (r2 > 0.05) with ABCC8 A1369S (rs757110), KCNJ11 E23K (rs5219), or SNPs in CAPN10 or HNFa. PPARG P12A (rs1801282) was not significantly associated with diabetes or related traits. CONCLUSION: Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at. Framingham 100K data replicate the TCF7L2 association with diabetes.National Heart, Lung, and Blood Institute's Framingham Heart Study (N01-HC-25195); National Institutes of Health National Center for Research Resources Shared Instrumentation grant (1S10RR163736-01A1); National Center for Research Resources General Clinical Research Center (M01-RR-01066); American Diabetes Association Career Developement Award; GlaxoSmithKline; Merck; Lilly; National Institutes of Health Research Career Award (K23 DK659678-03

Integral Field Spectroscopy of High-Redshift Star Forming Galaxies with Laser Guided Adaptive Optics: Evidence for Dispersion-Dominated Kinematics

We present early results from an ongoing study of the kinematic structure of star-forming galaxies at redshift z ~ 2 - 3 using integral-field spectroscopy of rest-frame optical nebular emission lines in combination with Keck laser guide star adaptive optics (LGSAO). We show kinematic maps of 3 target galaxies Q1623-BX453, Q0449-BX93, and DSF2237a-C2 located at redshifts z = 2.1820, 2.0067, and 3.3172 respectively, each of which is well-resolved with a PSF measuring approximately 0.11 - 0.15 arcsec (~ 900 - 1200 pc at z ~ 2-3) after cosmetic smoothing. Neither galaxy at z ~ 2 exhibits substantial kinematic structure on scales >~ 30 km/s; both are instead consistent with largely dispersion-dominated velocity fields with sigma ~ 80 km/s along any given line of sight into the galaxy. In contrast, DSF2237a-C2 presents a well-resolved gradient in velocity over a distance of ~ 4 kpc with peak-to-peak amplitude of 140 km/s. It is unlikely that DSF2237a-C2 represents a dynamically cold rotating disk of ionized gas as the local velocity dispersion of the galaxy (sigma = 79 km/s) is comparable to the observed shear. Using extant multi-wavelength spectroscopy and photometry we relate these kinematic data to physical properties such as stellar mass, gas fraction, star formation rate, and outflow kinematics and consider the applicability of current galaxy formation models.[Abridged]Comment: 19 pages, 10 figures (5 color); accepted for publication in ApJ. Version with full-resolution figures is available at http://www.astro.caltech.edu/~drlaw/Papers/OSIRIS_data1.pd

Communication: Diverse nanoscale cluster dynamics: Diffusion of 2D epitaxial clusters

The dynamics of nanoscale clusters can be distinct from macroscale behavior described by continuum formalisms. For diffusion of 2D clusters of N atoms in homoepitaxial systems mediated by edge atom hopping, macroscale theory predicts simple monotonic size scaling of the diffusion coefficient, DN ∼ N−β, with β = 3/2. However, modeling for nanoclusters on metal(100) surfaces reveals that slow nucleation-mediated diffusion displaying weak size scaling β \u3c 1 occurs for “perfect” sizes Np = L2 and L(L+1) for integer L = 3,4,… (with unique square or near-square ground state shapes), and also for Np+3, Np+4,…. In contrast, fast facile nucleation-free diffusion displaying strong size scaling β ≈ 2.5 occurs for sizes Np+1 and Np+2. DN versus N oscillates strongly between the slowest branch (for Np+3) and the fastest branch (for Np+1). All branches merge for N = O(102), but macroscale behavior is only achieved for much larger N = O(103). This analysis reveals the unprecedented diversity of behavior on the nanoscale

High-Resolution Electron-Impact Emission Spectrum of H 2 . I. Cross Sections and Emission Yields 900-1200 Å

High-resolution (Δλ = 115 mA) emission spectra of molecular hydrogen produced by electron-impact excitation at 100 eV have been obtained in the wavelength range 900-1200 A. The emission spectra can be assigned to transitions between the X 1Σ ground state and the 1sσgnpσu 1Σu and 1sσgnpπu 1Πu Rydberg states. Synthetic rotational line spectra based on the excitation function of Liu et al. and calculated 2pσ B 1Σ-X 1Σ, 2pπ C 1Πu-X 1Σ, 3pσ B' 1Σ-X 1Σ, and 3pπD 1Πu-X 1Σ transition probabilities of Abgrall et al. are generally found to be in good agreement with the experimental spectra in the regions where emissions from 1sσgnpσu (n ≥ 4) and 1sσgnpπu (n ≥ 4) states are negligible. Emission cross sections for D 1Π, D' 1Πu, and D'' 1Π, B' 1Σ, and B'' 1Σ states are obtained by measuring the emission intensities from these states relative to those from the B 1Σ,C 1Πu, and D 1Π states. A high- resolution EUV calibration technique is established. At 100 eV the emission cross sections of the D 1Πu, D' 1Πu, D'' 1Πu, B' 1Σ, and B'' 1Σ states are measured to be (2.8 ± 0.4) × 10-18, (6.3 ± 1.3) × 10-19, (5.9 ± 1.7) × 10-20, (2.1 ± 0.3) × 10-18, and (1.6 ± 0.4) × 10-19 cm2, respectively. In addition, the vibrational emission cross sections have been compared to the estimated excitation cross sections to obtain the predissociation yields for selected vibrational levels of the D 1Π, D' 1Π and D'' 1Π states. The B' 1Σ state is inferred to have very significant excitation into the H(1s)+H(2p,2s) dissociative continuum

Regulation-Structured Dynamic Metabolic Model Provides a Potential Mechanism for Delayed Enzyme Response in Denitrification Process

In a recent study of denitrification dynamics in hyporheic zone sediments, we observed a significant time lag (up to several days) in enzymatic response to the changes in substrate concentration. To explore an underlying mechanism and understand the interactive dynamics between enzymes and nutrients, we developed a trait-based model that associates a community’s traits with functional enzymes, instead of typically used species guilds (or functional guilds). This enzyme-based formulation allows to collectively describe biogeochemical functions of microbial communities without directly parameterizing the dynamics of species guilds, therefore being scalable to complex communities. As a key component of modeling, we accounted for microbial regulation occurring through transcriptional and translational processes, the dynamics of which was parameterized based on the temporal profiles of enzyme concentrations measured using a new signature peptide-based method. The simulation results using the resulting model showed several days of a time lag in enzymatic responses as observed in experiments. Further, the model showed that the delayed enzymatic reactions could be primarily controlled by transcriptional responses and that the dynamics of transcripts and enzymes are closely correlated. The developed model can serve as a useful tool for predicting biogeochemical processes in natural environments, either independently or through integration with hydrologic flow simulators

Extremely Red Objects in the Field of QSO 1213-0017: A Galaxy Concentration at z=1.31

We have discovered a concentration of extremely red objects (EROs; R-K>6) in the field of the z=2.69 quasar QSO 1213-0017 (UM 485), which is significantly overabundant compared to the field ERO surface density. The optical/near-IR colors of the EROs and numerous other red galaxies in this field are consistent with elliptical galaxies at z=1-2. HST optical images for a subset of galaxies show regular morphologies, most of them being disky or diffuse and without any obvious evidence for interactions. Ground-based IR images show similar morphologies, indicating any dust reddening in these objects is spatially uniform. Optical spectroscopy with the W. M. Keck Telescope has found that four of the red galaxies lie at =1.31, and a fifth lies in the foreground at z=1.20. Of the =1.31 galaxies, one is a reddened AGN while the remaining three have rest-frame UV absorption-line spectra characteristic of old (few Gyr) stellar populations, similar to the old red galaxy LBDS 53W091 at z=1.55. Including the MgII absorber seen in the QSO spectrum, we find five galaxies at =1.31 spread over 1.5 h_50^{-1} Mpc on the sky. These results suggest we have discovered a coherent structure of old galaxies at high-redshift, possibly associated with a massive galaxy cluster.Comment: 37 pages including 11 Postscript figures. To appear in the June 2000 issue of the Astronomical Journa

Regulation-Structured Dynamic Metabolic Model Provides a Potential Mechanism for Delayed Enzyme Response in Denitrification Process

In a recent study of denitrification dynamics in hyporheic zone sediments, we observed a significant time lag (up to several days) in enzymatic response to the changes in substrate concentration. To explore an underlying mechanism and understand the interactive dynamics between enzymes and nutrients, we developed a trait-based model that associates a community’s traits with functional enzymes, instead of typically used species guilds (or functional guilds). This enzyme-based formulation allows to collectively describe biogeochemical functions of microbial communities without directly parameterizing the dynamics of species guilds, therefore being scalable to complex communities. As a key component of modeling, we accounted for microbial regulation occurring through transcriptional and translational processes, the dynamics of which was parameterized based on the temporal profiles of enzyme concentrations measured using a new signature peptide-based method. The simulation results using the resulting model showed several days of a time lag in enzymatic responses as observed in experiments. Further, the model showed that the delayed enzymatic reactions could be primarily controlled by transcriptional responses and that the dynamics of transcripts and enzymes are closely correlated. The developed model can serve as a useful tool for predicting biogeochemical processes in natural environments, either independently or through integration with hydrologic flow simulators

Dislocation Kinks in Copper: Widths, Barriers, Effective Masses, and Quantum Tunneling

We calculate the widths, migration barriers, effective masses, and quantum tunneling rates of kinks and jogs in extended screw dislocations in copper, using an effective medium theory interatomic potential. The energy barriers and effective masses for moving a unit jog one lattice constant are close to typical atomic energies and masses: tunneling will be rare. The energy barriers and effective masses for the motion of kinks are unexpectedly small due to the spreading of the kinks over a large number of atoms. The effective masses of the kinks are so small that quantum fluctuations will be important. We discuss implications for quantum creep, kink--based tunneling centers, and Kondo resonances

A Giant Outburst at Millimeter Wavelengths in the Orion Nebula

BIMA observations of the Orion nebula discovered a giant flare from a young star previously undetected at millimeter wavelengths. The star briefly became the brightest compact object in the nebula at 86 GHz. Its flux density increased by more than a factor of 5 on a timescale of hours, to a peak of 160 mJy. This is one of the most luminous stellar radio flares ever observed. Remarkably, the Chandra X-ray observatory was in the midst of a deep integration of the Orion nebula at the time of the BIMA discovery; the source's X-ray flux increased by a factor of 10 approximately 2 days before the radio detection. Follow-up radio observations with the VLA and BIMA showed that the source decayed on a timescale of days, then flared again several times over the next 70 days, although never as brightly as during the discovery. Circular polarization was detected at 15, 22, and 43 GHz, indicating that the emission mechanism was cyclotron. VLBA observations 9 days after the initial flare yield a brightness temperature Tb > 5 x 10^7 K at 15 GHz. Infrared spectroscopy indicates the source is a K5V star with faint Br gamma emission, suggesting that it is a weak-line T Tauri object. Zeeman splitting measurements in the infrared spectrum find B ~ 2.6 +/- 1.0 kG. The flare is an extreme example of magnetic activity associated with a young stellar object. These data suggest that short observations obtained with ALMA will uncover hundreds of flaring young stellar objects in the Orion region.Comment: 29 pages, 7 figures, accepted for publication in Ap

A 4-unit-cell superstructure in optimally doped YBa2Cu3O6.92 superconductor

Using high-energy diffraction we show that a 4-unit-cell superstructure, q0=(1/4,0,0), along the shorter Cu-Cu bonds coexists with superconductivity in optimally doped YBCO. A complex set of anisotropic atomic displacements on neighboring CuO chain planes, BaO planes, and CuO2 planes, respectively, correlated over ~3-6 unit cells gives rise to diffuse superlattice peaks. Our observations are consistent with the presence of Ortho-IV nanodomains containing these displacements.Comment: Corrected typo in abstrac