Rigidity analysis of HIV-1 protease

We present a rigidity analysis on a large number of X-ray crystal structures of the enzyme HIV-1 protease using the 'pebble game' algorithm of the software FIRST. We find that although the rigidity profile remains similar across a comprehensive set of high resolution structures, the profile changes significantly in the presence of an inhibitor. Our study shows that the action of the inhibitors is to restrict the flexibility of the beta-hairpin flaps which allow access to the active site. The results are discussed in the context of full molecular dynamics simulations as well as data from NMR experiments.Comment: 4 pages, 3 figures. Conference proceedings for CMMP conference 2010 which was held at the University of Warwic

A transmission x ray microscopy and NEXAFS approach for studying corroded silicate glasses at the nanometre scale

In this study transmission X ray microscopy TXM was tested as a method to investigate the chemistry and structure of corroded silicate glasses at the nanometer scale. Three different silicate glasses were altered in static corrosion experiments for 1 336 hours at temperatures between 60 C and 85 C using a 25 HCl solution. Thin lamellas were cut perpendicular to the surface of corroded glass monoliths and were analysed with conventional TEM as well as with TXM. By recording optical density profiles at photon energies around the Na and O K edges, the shape of the corrosion rim pristine glass interfaces and the thickness of the corrosion rims has been determined. Na and O near edge X ray absorption fine structure spectra NEXAFS were obtained without inducing irradiation damage and have been used to detect chemical changes in the corrosion rims. Spatially resolved NEXAFS spectra at the O K edge provided insight to structural changes in the corrosion layer on the atomic scale. By comparison to O K edge spectra of silicate minerals and hydrous albite glass as well as to O K edge NEXAFS of model structures simulated with ab initio calculations, evidence is provided that changes of the fine structure at the O K edge are assigned to the formation of siloxane groups in the corrosion ri

A Central Partition of Molecular Conformational Space. IV. Extracting information from the graph of cells

In previous works [physics/0204035, physics/0404052, physics/0509126] a procedure was described for dividing the $3 \times N$-dimensional conformational space of a molecular system into a number of discrete cells, this partition allowed the building of a combinatorial structure from data sampled in molecular dynamics trajectories: the graph of cells, that encodes the set of cells in conformational space that are visited by the system in its thermal wandering. Here we outline a set of procedures for extracting useful information from this structure: 1st) interesting regions in the volume occupied by the system in conformational space can be bounded by a polyhedral cone whose faces are determined empirically from a set of relations between the coordinates of the molecule, 2nd) it is also shown that this cone can be decomposed into a hierarchical set of smaller cones, 3rd) the set of cells in a cone can be encoded by a simple combinatorial sequence.Comment: added an intrduction and reference

Determining Distribution and Size of Larval Pacific Geoduck Clams (Panopea Generosa Gould 1850) in Quartermaster Harbor (Washington, USA) Using a Novel Sampling Approach

Realistic species-specific information about larval life history is necessary for effective management of shellfish and parameterization of larval connectivity models. The patchiness of dispersing larvae, and the resources needed for sorting and identifying them, has limited many studies of larval distribution in the field, especially for species that are less common. In particular, little is known about in situ larval distribution of Pacific geoduck clams (Panopea generosa Gould 1850), a commercially important species found in Puget Sound, WA. A novel approach-time-integrating larval tube traps paired with molecular identification and sorting (FISH-CS)-was used to determine the distribution of geoduck larvae over 4 moat 3 stations in Quartermaster Harbor. Larvae were found consistently at the surface and thermocline rather than at the bottom. More and larger larvae were captured in the inside and middle of the harbor than the outer harbor, indicating at least some larval retention. Two pulses of larvae were captured, in March and late May to early June. Size frequency distributions of larvae indicate that these were 2 separate cohorts of larvae, with the possibility of a pulse of larvae from elsewhere toward the end of the season. The only physical parameter associated with relative larval abundance was degree of stratification, although the association was weak. These data represent the first reported study of geoduck larval distribution in the field and the first use of the FISH-CS technique for field collections. In the future, this approach can be used to answer many relevant management questions locally and more broadly, including quantifying larval export from shellfish farms, placement of restoration sites and marine protected areas, and spread of invasive species

Scaling of Island Growth in Pb Overlayers on Cu(001)

The growth and ordering of a Pb layer deposited on Cu(001) at 150 K has been studied using atom beam scattering. At low coverage, ordered Pb islands with a large square unit cell and nearly hexagonal internal structure are formed. This is a high order commensurate phase with 30 atoms in the unit cell. From the measurement of the island diffraction peak profiles we find a power law for the mean island - size versus coverage with an exponent $n=0.54 \pm 0.03$. A scaling behavior of growth is confirmed and a simple model describing island growth is presented. Due to the high degeneracy of the monolayer phase, different islands do not diffract coherently. Therefore, when islands merge they still diffract as separate islands and coalescence effects are thus negligible. From the result for $n$ we conclude that the island density is approximately a constant in the coverage range $0.1 < \Theta < 0.5$ where the ordered islands are observed. We thus conclude that most islands nucleate at $\Theta < 0.1$ and then grow in an approximately self similar fashion as $\Theta$ increases.Comment: 23 pages, 10 Figures (available upon request). SU-PHYS-93-443-375

Two-domains bulklike Fermi surface of Ag films deposited onto Si(111)-(7x7)

Thick metallic silver films have been deposited onto Si(111)-(7x7) substrates at room temperature. Their electronic properties have been studied by using angle resolved photoelectron spectroscopy (ARPES). In addition to the electronic band dispersion along the high-symmetry directions, the Fermi surface topology of the grown films has been investigated. Using ARPES, the spectral weight distribution at the Fermi level throughout large portions of the reciprocal space has been determined at particular perpendicular electron-momentum values. Systematically, the contours of the Fermi surface of these films reflected a sixfold symmetry instead of the threefold symmetry of Ag single crystal. This loss of symmetry has been attributed to the fact that these films appear to be composed by two sets of domains rotated 60$^o$ from each other. Extra, photoemission features at the Fermi level were also detected, which have been attributed to the presence of surface states and \textit{sp}-quantum states. The dimensionality of the Fermi surface of these films has been analyzed studying the dependence of the Fermi surface contours with the incident photon energy. The behavior of these contours measured at particular points along the Ag $\Gamma$L high-symmetry direction puts forward the three-dimensional character of the electronic structure of the films investigated.Comment: 10 pages, 12 figures, submitted to Physical Review

Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P&lt;0.0001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly greater than or equal to1200?ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR, 3.2 [1.1–9.6]; P=0.01) and elevated AP (HR 2.6 [1.0–7.1]; P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76% and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate-risk, n=28) or 2 (high-risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the WHO classification and provide the most relevant prognostic information in SM patient

Evaluating signatures of glacial refugia for North Atlantic benthic marine taxa

A goal of phylogeography is to relate patterns of genetic differentiation to potential historical geographic isolating events. Quaternary glaciations, particularly the one culminating in the Last Glacial Maximum ;21 ka (thousands of years ago), greatly affected the distributions and population sizes of temperate marine species as their ranges retreated southward to escape ice sheets. Traditional genetic models of glacial refugia and routes of recolonization include these predictions: low genetic diversity in formerly glaciated areas, with a small number of alleles/ haplotypes dominating disproportionately large areas, and high diversity including ‘‘private’’ alleles in glacial refugia. In the Northern Hemisphere, low diversity in the north and high diversity in the south are expected. This simple model does not account for the possibility of populations surviving in relatively small northern periglacial refugia. If these periglacial populations experienced extreme bottlenecks, they could have the low genetic diversity expected in recolonized areas with no refugia, but should have more endemic diversity (private alleles) than recently recolonized areas. This review examines evidence of putative glacial refugia for eight benthic marine taxa in the temperate North Atlantic. All data sets were reanalyzed to allow direct comparisons between geographic patterns of genetic diversity and distribution of particular clades and haplotypes including private alleles. We contend that for marine organisms the genetic signatures of northern periglacial and southern refugia can be distinguished from one another. There is evidence for several periglacial refugia in northern latitudes, giving credence to recent climatic reconstructions with less extensive glaciation

Electronic properties and Fermi surface of Ag(111) films deposited onto H-passivated Si(111)-(1x1) surfaces

Silver films were deposited at room temperature onto H-passivated Si(111) surfaces. Their electronic properties have been analyzed by angle-resolved photoelectron spectroscopy. Submonolayer films were semiconducting and the onset of metallization was found at a Ag coverage of $\sim$0.6 monolayers. Two surface states were observed at $\bar{\Gamma}$-point in the metallic films, with binding energies of 0.1 and 0.35 eV. By measurements of photoelectron angular distribution at the Fermi level in these films, a cross-sectional cut of the Fermi surface was obtained. The Fermi vector determined along different symmetry directions and the photoelectron lifetime of states at the Fermi level are quite close to those expected for Ag single crystal. In spite of this concordance, the Fermi surface reflects a sixfold symmetry rather than the threefold symmetry of Ag single crystal. This behavior was attributed to the fact that these Ag films are composed by two domains rotated 60$^o$.Comment: 9 pages, 8 figures, submitted to Physical Review