2,500 research outputs found

    Organisational resilience following the Darfield earthquake of 2010

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    This paper presents the preliminary findings of a study on the resilience and recovery of organisations following the Darfield earthquake in New Zealand on 4 September 2010. Sampling included organisations proximal and distal to the fault trace, organisations located within central business districts, and organisations from seven diverse industry sectors. The research captured information on the challenges to, the impacts on, and the reflections of the organisations in the first months of recovery. Organisations in central business districts and in the hospitality sector were most likely to close while organisations that had perishable stock and livestock were more heavily reliant on critical services. Staff well-being, cash flow, and customer loss were major concerns for organisations across all sectors. For all organisations, the most helpful factors in mitigating the effects of the earthquake to be their relationship with staff, the design and type of buildings, and critical service continuity or swift reinstatement of services

    The Structure of GaSb Digitally Doped with Mn

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    Cross sectional scanning tunneling microscopy (XSTM) and density functional theory have been used to characterize the structure of GaSb digitally doped with Mn. The Mn dopants are found in both isolated substitutional form as well as in large clusters of zinc-blende MnSb commensurate with the surrounding GaSb matrix. Theoretical calculations predict that these two forms of Mn in the digitally doped layers will have a very different appearance in XSTM images. Substitutional Mn enhances the local density of states near the surface, thus appearing higher in a filled-state image. In contrast, MnSb clusters induce substantial structural relaxation at the {110} surface, and therefore appear as localized depressed regions with negligible perturbation of the surrounding GaSb.Comment: 10 pages, 5 figures, submitted to PRB Brief Report, revised versio

    Localized Excitons and Breaking of Chemical Bonds at III-V (110) Surfaces

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    Electron-hole excitations in the surface bands of GaAs(110) are analyzed using constrained density-functional theory calculations. The results show that Frenkel-type autolocalized excitons are formed. The excitons induce a local surface unrelaxation which results in a strong exciton-exciton attraction and makes complexes of two or three electron-hole pairs more favorable than separate excitons. In such microscopic exciton "droplets" the electron density is mainly concentrated in the dangling orbital of a surface Ga atom whereas the holes are distributed over the bonds of this atom to its As neighbors thus weakening the bonding to the substrate. This finding suggests the microscopic mechanism of a laser-induced emission of neutral Ga atoms from GaAs and GaP (110) surfaces.Comment: submitted to PRL, 10 pages, 4 figures available upon request from: [email protected]

    Structure of the Proline Utilization A Proline Dehydrogenase Domain Inactivated by \u3ci\u3eN\u3c/i\u3e-propargylglycine Provides Insight into Conformational Changes Induced by Substrate Binding and Flavin Reduction

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    Proline utilization A (PutA) from Escherichia coli is a flavoprotein that has mutually exclusive roles as a transcriptional repressor of the put regulon and a membrane-associated enzyme that catalyzes the oxidation of proline to glutamate. Previous studies have shown that the binding of proline in the proline dehydrogenase (PRODH) active site and subsequent reduction of the FAD trigger global conformational changes that enhance PutA-membrane affinity. These events cause PutA to switch from its repressor to enzymatic role, but the mechanism by which this signal is propagated from the active site to the distal membrane-binding domain is largely unknown. Here, it is shown that N-propargylglycine irreversibly inactivates PutA by covalently linking the flavin N(5) atom to the ε-amino of Lys329. Furthermore, inactivation locks PutA into a conformation that may mimic the proline reduced, membrane-associated form. The 2.15 Å resolution structure of the inactivated PRODH domain suggests that the initial events involved in broadcasting the reduced flavin state to the distal membrane binding domain include major reorganization of the flavin ribityl chain, severe (35 degree) butterfly bending of the isoalloxazine ring, and disruption of an electrostatic network involving the flavin N(5), Arg431, and Asp370. The structure also provides information about conformational changes associated with substrate binding. This analysis suggests that the active site is incompletely assembled in the absence of the substrate, and the binding of proline draws together conserved residues in helix 8 and the β1-αl loop to complete the active site

    A Richness Study of 14 Distant X-ray Clusters From the 160 Square Degree Survey

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    We have measured the surface density of galaxies toward 14 X-ray-selected cluster candidates at redshifts greater than z=0.46, and we show that they are associated with rich galaxy concentrations. We find that the clusters range between Abell richness classes 0-2, and have a most probable richness class of one. We compare the richness distribution of our distant clusters to those for three samples of nearby clusters with similar X-ray luminosities. We find that the nearby and distant samples have similar richness distributions, which shows that clusters have apparently not evolved substantially in richness since redshift z =0.5. We compare the distribution of distant X-ray clusters in the L_x--richness plane to the distribution of optically-selected clusters from the Palomar Distant Cluster Survey. The optically-selected clusters appear overly rich for their X-ray luminosities when compared to X-ray-selected clusters. Apparently, X-ray and optical surveys do not necessarily sample identical mass concentrations at large redshifts. This may indicate the existence of a population of optically rich clusters with anomalously low X-ray emission. More likely, however, it reflects the tendency for optical surveys to select unvirialized mass concentrations, as might be expected when peering along large-scale filaments.Comment: The abstract has been abridged. Accepted for publication in the Astrophysical Journa

    Hematologic Safety of Chronic Brain-Penetrating Erythropoietin Dosing in APP/PS1 Mice

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    Introduction: Low blood-brain barrier (BBB) penetration and hematopoietic side effects limit the therapeutic development of erythropoietin (EPO) for Alzheimer\u27s disease (AD). A fusion protein of EPO and a chimeric monoclonal antibody targeting the mouse transferrin receptor (cTfRMAb) has been engineered. The latter drives EPO into the brain via receptor-mediated transcytosis across the BBB and increases its peripheral clearance to reduce hematopoietic side effects of EPO. Our previous work shows the protective effects of this BBB-penetrating EPO in AD mice but hematologic effects have not been studied. Herein, we investigate the hematologic safety and therapeutic effects of chronic cTfRMAb-EPO dosing, in comparison to recombinant human EPO (rhu-EPO), in AD mice. Methods: Male APPswe PSEN1dE9 (APP/PS1) mice (9.5 months) were treated with saline (n = 11), and equimolar doses of cTfRMAb-EPO (3 mg/kg, n = 7), or rhu-EPO (0.6 mg/kg, n = 9) 2 days/week subcutaneously for 6 weeks, compared to saline-treated wild-type mice (n = 10). At 6 weeks, exploration and memory were assessed, and mice were sacrificed at 8 weeks. Spleens were weighed, and brains were evaluated for amyloid beta (Aβ) load and synaptophysin. Blood was collected at 4, 6 and 8 weeks for a complete blood count and white blood cells differential. Results: cTfRMAb-EPO transiently increased reticulocyte counts after 4 weeks, followed by normalization of reticulocytes at 6 and 8 weeks. rhu-EPO transiently increased red blood cell count, hemoglobin and hematocrit, and significantly decreased mean corpuscular volume and reticulocytes at 4 weeks, which remained low at 6 weeks. At 8 weeks, a significant decline in red blood cell indices was observed with rhu-EPO treatment. Exploration and cognitive deficits were significantly worse in APP/PS1-rhu-EPO mice. Both cTfRMAb-EPO and rhu-EPO decreased 6E10-positive brain Aβ load; however, cTfRMAb-EPO and not rhu-EPO selectively reduced brain Aβ1-42 and elevated synaptophysin expression. Discussion: Chronic treatment with cTfRMAb-EPO results in better hematologic safety, behavioral, and therapeutic indices compared with rhu-EPO, supporting the development of this BBB-penetrable EPO analog for AD. therapeutic indices compared with rhu-EPO, supporting the development of this BBB-penetrable EPO analog for AD

    Asymptotic Structure of Symmetry Reduced General Relativity

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    Gravitational waves with a space-translation Killing field are considered. In this case, the 4-dimensional Einstein vacuum equations are equivalent to the 3-dimensional Einstein equations with certain matter sources. This interplay between 4- and 3- dimensional general relativity can be exploited effectively to analyze issues pertaining to 4 dimensions in terms of the 3-dimensional structures. An example is provided by the asymptotic structure at null infinity: While these space-times fail to be asymptotically flat in 4 dimensions, they can admit a regular completion at null infinity in 3 dimensions. This completion is used to analyze the asymptotic symmetries, introduce the analog of the 4-dimensional Bondi energy-momentum and write down a flux formula. The analysis is also of interest from a purely 3-dimensional perspective because it pertains to a diffeomorphism invariant 3-dimensional field theory with {\it local} degrees of freedom, i.e., to a midi-superspace. Furthermore, due to certain peculiarities of 3 dimensions, the description of null infinity does have a number of features that are quite surprising because they do not arise in the Bondi-Penrose description in 4 dimensions.Comment: 39 Pages, REVTEX, CGPG-96/5-

    GAS6 expression identifies high-risk adult AML patients: potential implications for therapy

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    Emerging data demonstrate important roles for the TYRO3/AXL/MERTK receptor tyrosine kinase (TAM RTK) family in diverse cancers. We investigated the prognostic relevance of GAS6 expression, encoding the common TAM RTK ligand, in 270 adults (n=71 aged \u3c60 \u3eyears; n=199 aged \u3e= 60 years) with de novo cytogenetically normal acute myeloid leukemia (CN-AML). Patients expressing GAS6 (GAS6+), especially those aged \u3e= 60 years, more often failed to achieve a complete remission (CR). In all patients, GAS6+ patients had shorter disease-free (DFS) and overall (OS) survival than patients without GAS6 expression (GAS6-). After adjusting for other prognostic markers, GAS6+ predicted CR failure (P=0.02), shorter DFS (P=0.004) and OS (P=0.04). To gain further biological insights, we derived a GAS6-associated gene-expression signature (

    Plasma-binding globulins and acute stress response

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    Within studies of acute stress physiology an increase in glucocorticoid secretion is thought to be the primary mediator of tissue response to stress. Corticosteroid-binding globulin may regulate tissue availability of steroids, but has not been considered a dynamic component of the acute stress response. Here, we examined CBG level over the common 60-minute time frame in an acute capture and handling protocol to investigate whether CBG capacity is dynamic or static over short stressors. Using a comparative approach, we measured CBG response to capture and handling stress in nine species of birds, representing five orders and nine families. CBG capacity significantly declined within 30-60 minutes of capture in five of the nine species examined. This decline may serve to significantly increase the level of corticosterone reaching tissues during acute stress. © Georg Thieme Verlag KG Stuttgart
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