The Dynamic Structure of Thrombin in Solution

AbstractThe backbone dynamics of human α-thrombin inhibited at the active site serine were analyzed using R1, R2, and heteronuclear NOE experiments, variable temperature TROSY 2D [1H-15N] correlation spectra, and Rex measurements. The N-terminus of the heavy chain, which is formed upon zymogen activation and inserts into the protein core, is highly ordered, as is much of the double beta-barrel core. Some of the surface loops, by contrast, remain very dynamic with order parameters as low as 0.5 indicating significant motions on the ps-ns timescale. Regions of the protein that were thought to be dynamic in the zymogen and to become rigid upon activation, in particular the γ-loop, the 180s loop, and the Na+ binding site have order parameters below 0.8. Significant Rex was observed in most of the γ-loop, in regions proximal to the light chain, and in the β-sheet core. Accelerated molecular dynamics simulations yielded a molecular ensemble consistent with measured residual dipolar couplings that revealed dynamic motions up to milliseconds. Several regions, including the light chain and two proximal loops, did not appear highly dynamic on the ps-ns timescale, but had significant motions on slower timescales

Revising the Local Bubble Model due to Solar Wind Charge Exchange X-ray Emission

The hot Local Bubble surrounding the solar neighborhood has been primarily studied through observations of its soft X-ray emission. The measurements were obtained by attributing all of the observed local soft X-rays to the bubble. However, mounting evidence shows that the heliosphere also produces diffuse X-rays. The source is solar wind ions that have received an electron from another atom. The presence of this alternate explanation for locally produced diffuse X-rays calls into question the existence and character of the Local Bubble. This article addresses these questions. It reviews the literature on solar wind charge exchange (SWCX) X-ray production, finding that SWCX accounts for roughly half of the observed local 1/4 keV X-rays found at low latitudes. This article also makes predictions for the heliospheric O VI column density and intensity, finding them to be smaller than the observational error bars. Evidence for the continued belief that the Local Bubble contains hot gas includes the remaining local 1/4 keV intensity, the observed local O VI column density, and the need to fill the local region with some sort of plasma. If the true Local Bubble is half as bright as previously thought, then its electron density and thermal pressure are 1/square-root(2) as great as previously thought, and its energy requirements and emission measure are 1/2 as great as previously thought. These adjustments can be accommodated easily, and, in fact, bring the Local Bubble's pressure more in line with that of the adjacent material. Suggestions for future work are made.Comment: 9 pages, refereed, accepted for publication in the proceedings of the "From the Outer Heliosphere to the Local Bubble: Comparisons of New Observations with Theory" conference and in Space Science Review

Arrested kinetic Li isotope fractionation at the margin of the llimaussaq complex, South Greenland: Evidence for open-system processes during final cooling of peralkaline igneous rocks

Li contents [Li] and isotopic composition (delta Li-7) of mafic minerals (mainly amphibole and clinopyroxene) from the alkaline to peralkaline Ilimaussaq plutonic complex, South Greenland, track the behavior of Li and its isotopes during magmatic differentiation and final cooling of an alkaline igneous system. [Li] in amphibole increase from < 10 ppm in Caamphiboles of the least differentiated unit to >3000 ppm in Na-amphiboles of the highly evolved units. In contrast, [Li] in clinopyroxene are comparatively low (<85 ppm) and do not vary systematically with differentiation. The distribution of Li between amphibole and pyroxene is controlled by the major element composition of the minerals (Ca-rich and Na-rich, respectively) and changes in oxygen fugacity (due to Li incorporation via coupled substitution with ferric iron) during magmatic differentiation. delta(7) Li values of all minerals span a wide range from + 17 to - 8 parts per thousand, with the different intrusive units of the complex having distinct Li isotopic systematics. Amphiboles, which dominate the Li budget of whole-rocks from the inner part of the complex, have constant delta Li-7 of + 1.8 +/- 2.2 parts per thousand (2 sigma, n = 15). This value reflects a homogeneous melt reservoir and is consistent with their mantle derivation, in agreement with published O and Nd isotopic data. Clinopyroxenes of these samples are consistently lighter, with Delta Li-7(amph-cpx). as large as 8 parts per thousand and are thus not in Li isotope equilibrium. These low values probably reflect late-stage diffusion of Li into clinopyroxene during final cooling of the rocks, thus enriching the clinopyroxene in 6 Li. At the margin of the complex delta(7) Li in the syenites increases systematically, from +2 to high values of + 14 parts per thousand. This, coupled with the observed Li isotope systematics of the granitic country rocks, reflects post-magmatic open-system processes occurring during final cooling of the intrusion. Although the shape and magnitude of the Li isotope and elemental profiles through syenite and country rock are suggestive of diffusion-driven isotope fractionation, they cannot be modeled by one-dimensional diffusive transport and point to circulation of a fluid having a high 67 Li value (possibly seawater) along the chilled contact. In all, this study demonstrates that Li isotopes can be used to identify complex fluid- and diffusion-governed processes taking place during the final cooling of such rocks. (c) 2007 Elsevier B.V All rights reserved

Fabrication process responsible for fundamentally improving Silicon X-ray microcalorimeter arrays

We have developed an improved microcalorimeter array that will be used on the AstroE-2 satellite mission. The 6×6 array consists of a grid of 36 suspended pixels. Each 1.5μm thick pixel has an ion-implanted thermometer, four thermal links (support beams), and four X-ray absorber support tabs. Improvements in Silicon micro-machining capabilities and the availability of custom Silicon-on-Insulator (SOI) wafers has enabled us to precisely control pixel geometry, lead widths, and develop a more compact array. Knowing the silicon thickness, we can calculate a precise implant dose for the thermometer. Using a high-temperature anneal, we can uniformly diffuse the implant throughout the depth of the top layer of the SOI wafer. Defining the length, width, and thickness of the support beams, we can control the thermal conductance of the pixel. Advancements in polymer-photo resists have enabled us to develop a new absorber support tab attachment scheme resulting in more controlled heat dissipation from the absorber to the thermometer on the pixel. An overview of fabrication improvements focusing on these topics will be discussed

Cosmic ray effects in microcalorimeter arrays

We have identified signals resulting from cosmic rays and environmental gamma rays depositing energy in the pixels and in the silicon frame of the Astro-E2/X-Ray Spectrometer microcalorimeter array. Coincidences between pixels and between the array and an anti-coincidence detector determined the nature of the events. Pulse shapes and amplitudes from the cosmic ray events helped refine the thermal model of the array chip. We discuss how future arrays can be optimized either for the greatest background rejection or for the highest source count rates

High-resolution calorimetry: limitations of doped semiconductor thermometers

Small thermal calorimeters operating at cryogenic temperatures have achieved an energy resolution for single X-ray photons that is a factor of 20 better than the theoretical limit for a silicon ionization detector. To determine the potential for further improvements and decide on likely routes for achieving them, we discuss detector design optimization, first for an ideal calorimeter, and then for the case where components exhibit non-ideal behavior. Two serious non-ideal properties of doped semiconductor thermometers are electron–phonon decoupling and excess noise. These have been characterized over a range of sensitivity and operating temperature, and their effects on design optimization and ultimate performance can be evaluated

Design of the second generation XRS detector

Microcalorimeter performance is limited by non-ideal effects that were not included in the standard theory of bolometers and microcalorimeters developed 20 years ago by Mather (Appl. Opt. 21 (1982) 1125). These include the hot-electron effect, absorber decoupling, thermometer non-ohmic behavior, and all related extra noise sources. Models that include these effects have been developed and can be used to optimize the design of microcalorimeters for best performance. The design of the array for the XRS detector on the Astro-E2 satellite was completely optimized based on the required performance and on the characteristics of the materials used. The characteristic heat capacity and thermal conductivity of all the detector components have been measured and the values have been used as input to the models to design the detector geometry for best performance. Mechanical modeling has also been carried out in parallel to ensure the mechanical integrity of the microcalorimeter. We report here the analysis involved in the optimization of the detectors, and the comparison between modeled and measured performance

The next-generation microcalorimeter array of XRS on Astro-E2

The square-format 32-pixel microcalorimeter array at the focal plane of the high-resolution X-ray spectrometer on the Astro-E2 X-ray Observatory is the first of a new generation of silicon-based microcalorimeters. This array has numerous advantages over its predecessor, the bilinear array that was launched on Astro-E. Foremost among its benefits are: (1) the energy resolution is improved by a factor of two at 6keV (now 6eV FWHM), (2) the thermal time constant is a factor of two faster, and (3) each pixel has a Gaussian line response. We will discuss the design changes that have led to these and other advantages