365 research outputs found
Reduction of myocardial infarction by postischemic administration of the calpain inhibitor A-705253 in comparison to the Na(+)/H(+) exchange inhibitor Cariporide (R) in isolated perfused rabbit hearts
The calpain inhibitor A-705253 and the Na(+)/H(+) exchange inhibitor Cariporide (R) were studied in isolated perfused rabbit hearts subjected to 60 min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid solely or in combination at the beginning of reperfusion. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were performed. Myocardial infarct size and area at risk (transiently not perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 72.7 +/- 4.0% of the area at risk in untreated controls, but was significantly smaller in the presence of the inhibitors. The largest effect was observed with 10(-6) M A-705253, which reduced the infarcted area to 49.2 +/- 4.1% of the area at risk, corresponding to a reduction of 33.6%. Cariporide (R) at 10(-6) M reduced the infarct size to the same extent. The combination of both inhibitors, however, did not further improve cardioprotection. No significant difference was observed between the experimental groups in coronary perfusion, left ventricular pressure, heart rate, or in the release of lactate dehydrogenase and creatine kinase from heart muscle
Quark matter nucleation in hot hadronic matter
We study the quark deconfinement phase transition in hot -stable
hadronic matter. Assuming a first order phase transition, we calculate the
enthalpy per baryon of the hadron-quark phase transition. We calculate and
compare the nucleation rate and the nucleation time due to thermal and quantum
nucleation mechanisms. We compute the crossover temperature above which thermal
nucleation dominates the finite temperature quantum nucleation mechanism. We
next discuss the consequences for the physics of proto-neutron stars. We
introduce the concept of limiting conversion temperature and critical mass
for proto-hadronic stars, and we show that proto-hadronic stars with a
mass could survive the early stages of their evolution without
decaying to a quark star
The Dislocation Stress Functions From the Double Curl T(3)-Gauge Equation: Linearity and a Look Beyond
T(3)-gauge model of defects based on the gauge Lagrangian quadratic in the
gauge field strength is considered. The equilibrium equation of the medium is
fulfilled by the double curl Kroner's ansatz for stresses. The problem of
replication of the static edge dislocation along third axis is analysed under a
special, though conventional, choice of this ansatz. The translational gauge
equation is shown to constraint the functions parametrizing the ansatz (the
stress functions) so that the resulting stress component is not
that of the edge defect. Another translational gauge equation with the double
curl differential operator is shown to reproduce both the stress functions, as
well as the stress tensors, of the standard edge and screw dislocations.
Non-linear extension of the newly proposed translational gauge equation is
given to correct the linear defect solutions in next orders. New gauge
Lagrangian is suggested in the Hilbert-Einstein form.Comment: 21 pages, LaTeX, no figure
PVP2008-61762 DESIGN AND MANUFACTURE OF WELDED PLATE SPECIMENS FOR RESIDUAL STRESS EXPERIMENTS
ABSTRACT A long-term UK research programme has been established in order to improve the understanding of thermo-mechanical behaviour and residual stresses generated in pressure vessel steel welds as well as developing finite element (FE) welding simulation methods. The production of representative test specimens is an important element of this research project, since quality measurement data are needed to validate FE models. This paper describes the design, development and manufacture of welded plate specimens used for residual stress (RS) experiments. To date, research has focused mainly on developing the understanding of SA508 pressure vessel steel welds. Specimen dimensions were selected to facilitate stress measurements using a range of techniques. The philosophy adopted was to start with relatively simple 1-pass weld specimens and gradually increase the complexity to multi-pass groove welds in plates. Simple 1-pass weld specimens were generally designed to investigate the effect of welding parameters on thermomechanical behaviour, such as heat-affected zone (HAZ) microstructures and phase transformations. Later specimens are more representative of multi-pass power plant welds. They are being used to study material thermal cyclic hardening/softening behaviour. Other issues of concern are also being investigated, such as the effect of restraint during welding on RS and the effectiveness of post weld heat treatment (PWHT). Specimens were also designed to study peak stresses arising at bead stop/start positions and whether such peak stresses are annealed in overlaying additional weld metal. These investigations were performed on multi-pass groove welds in both austenitic and ferritic steel plates. Practical issues encountered during welding trials are discussed, including plate distortion and magnetisation of the ferritic steel plates. Information is also provided about welding temperature measurements and metallurgical examinations
Homogeneous nucleation of quark-gluon plasma, finite size effects and long-lived metastable objects
The general formalism of homogeneous nucleation theory is applied to study
the hadronization pattern of the ultra-relativistic quark-gluon plasma (QGP)
undergoing a first order phase transition. A coalescence model is proposed to
describe the evolution dynamics of hadronic clusters produced in the nucleation
process. The size distribution of the nucleated clusters is important for the
description of the plasma conversion. The model is most sensitive to the
initial conditions of the QGP thermalization, time evolution of the energy
density, and the interfacial energy of the plasma-hadronic matter interface.
The rapidly expanding QGP is first supercooled by about . Then it reheats again up to the critical temperature T_c. Finally it
breaks up into hadronic clusters and small droplets of plasma. This fast
dynamics occurs within the first . The finite size effects and
fluctuations near the critical temperature are studied. It is shown that a drop
of longitudinally expanding QGP of the transverse radius below 4.5 fm can
display a long-lived metastability. However, both in the rapid and in the
delayed hadronization scenario, the bulk pion yield is emitted by sources as
large as 3-4.5 fm. This may be detected experimentally both by a HBT
interferometry signal and by the analysis of the rapidity distributions of
particles in narrow p_T-intervals at small p_T on an event-by-event basis.Comment: 29 pages, incl. 12 figures and 1 table; to be published in Phys. Rev.
Dynamical Viscosity of Nucleating Bubbles
We study the viscosity corrections to the growth rate of nucleating bubbles
in a first order phase transition in scalar field theory. We obtain the
non-equilibrium equation of motion of the coordinate that describes small
departures from the critical bubble and extract the growth rate consistently in
weak coupling and in the thin wall limit. Viscosity effects arise from the
interaction of this coordinate with the stable quantum and thermal fluctuations
around a critical bubble. In the case of 1+1 dimensions we provide an estimate
for the growth rate that depends on the details of the free energy functional.
In 3+1 dimensions we recognize robust features that are a direct consequence of
the thin wall approximation and give the leading viscosity corrections.These
are long-wavelength hydrodynamic fluctuations that describe surface waves,
quasi-Goldstone modes which are related to ripples on interfaces in phase
ordered Ising-like systems. We discuss the applicability of our results to
describe the growth rate of hadron bubbles in a quark-hadron first order
transition.Comment: 40 pages, 4 figures, revtex, minor changes, to be published in Phys.
Rev.
A CDC20-APC/SOX2 Signaling Axis Regulates Human Glioblastoma Stem-like Cells
SummaryGlioblastoma harbors a dynamic subpopulation of glioblastoma stem-like cells (GSCs) that can propagate tumors in vivo and is resistant to standard chemoradiation. Identification of the cell-intrinsic mechanisms governing this clinically important cell state may lead to the discovery of therapeutic strategies for this challenging malignancy. Here, we demonstrate that the mitotic E3 ubiquitin ligase CDC20-anaphase-promoting complex (CDC20-APC) drives invasiveness and self-renewal in patient tumor-derived GSCs. Moreover, CDC20 knockdown inhibited and CDC20 overexpression increased the ability of human GSCs to generate brain tumors in an orthotopic xenograft model in vivo. CDC20-APC control of GSC invasion and self-renewal operates through pluripotency-related transcription factor SOX2. Our results identify a CDC20-APC/SOX2 signaling axis that controls key biological properties of GSCs, with implications for CDC20-APC-targeted strategies in the treatment of glioblastoma
Syntaxin 5 Is Required for Copper Homeostasis in Drosophila and Mammals
Copper is essential for aerobic life, but many aspects of its cellular uptake and distribution remain to be fully elucidated. A genome-wide screen for copper homeostasis genes in Drosophila melanogaster identified the SNARE gene Syntaxin 5 (Syx5) as playing an important role in copper regulation; flies heterozygous for a null mutation in Syx5 display increased tolerance to high dietary copper. The phenotype is shown here to be due to a decrease in copper accumulation, a mechanism also observed in both Drosophila and human cell lines. Studies in adult Drosophila tissue suggest that very low levels of Syx5 result in neuronal defects and lethality, and increased levels also generate neuronal defects. In contrast, mild suppression generates a phenotype typical of copper-deficiency in viable, fertile flies and is exacerbated by co-suppression of the copper uptake gene Ctr1A. Reduced copper uptake appears to be due to reduced levels at the plasma membrane of the copper uptake transporter, Ctr1. Thus Syx5 plays an essential role in copper homeostasis and is a candidate gene for copper-related disease in humans
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