2,500 research outputs found
Organisational resilience following the Darfield earthquake of 2010
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
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
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
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
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
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
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-
Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.
GAS6 expression identifies high-risk adult AML patients: potential implications for therapy
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
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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