503 research outputs found
Geometric phase outside a Schwarzschild black hole and the Hawking effect
We study the Hawking effect in terms of the geometric phase acquired by a
two-level atom as a result of coupling to vacuum fluctuations outside a
Schwarzschild black hole in a gedanken experiment. We treat the atom in
interaction with a bath of fluctuating quantized massless scalar fields as an
open quantum system, whose dynamics is governed by a master equation obtained
by tracing over the field degrees of freedom. The nonunitary effects of this
system are examined by analyzing the geometric phase for the Boulware, Unruh
and Hartle-Hawking vacua respectively. We find, for all the three cases, that
the geometric phase of the atom turns out to be affected by the space-time
curvature which backscatters the vacuum field modes. In both the Unruh and
Hartle-Hawking vacua, the geometric phase exhibits similar behaviors as if
there were thermal radiation at the Hawking temperature from the black hole.
So, a measurement of the change of the geometric phase as opposed to that in a
flat space-time can in principle reveal the existence of the Hawking radiation.Comment: 14 pages, no figures, a typo in the References corrected, version to
appear in JHEP. arXiv admin note: text overlap with arXiv:1109.033
B cells and monocytes from patients with active multiple sclerosis exhibit increased surface expression of both HERV-H Env and HERV-W Env, accompanied by increased seroreactivity
<p>Abstract</p> <p>Background</p> <p>The etiology of the neurogenerative disease multiple sclerosis (MS) is unknown. The leading hypotheses suggest that MS is the result of exposure of genetically susceptible individuals to certain environmental factor(s). Herpesviruses and human endogenous retroviruses (HERVs) represent potentially important factors in MS development. Herpesviruses can activate HERVs, and HERVs are activated in MS patients.</p> <p>Results</p> <p>Using flow cytometry, we have analyzed HERV-H Env and HERV-W Env epitope expression on the surface of PBMCs from MS patients with active and stable disease, and from control individuals. We have also analyzed serum antibody levels to the expressed HERV-H and HERV-W Env epitopes. We found a significantly higher expression of HERV-H and HERV-W Env epitopes on B cells and monocytes from patients with active MS compared with patients with stable MS or control individuals. Furthermore, patients with active disease had relatively higher numbers of B cells in the PBMC population, and higher antibody reactivities towards HERV-H Env and HERV-W Env epitopes. The higher antibody reactivities in sera from patients with active MS correlate with the higher levels of HERV-H Env and HERV-W Env expression on B cells and monocytes. We did not find such correlations for stable MS patients or for controls.</p> <p>Conclusion</p> <p>These findings indicate that both HERV-H Env and HERV-W Env are expressed in higher quantities on the surface of B cells and monocytes in patients with active MS, and that the expression of these proteins may be associated with exacerbation of the disease.</p
Border Terriers under primary veterinary care in England: demography and disorders
The Border Terrier is a working terrier type that is generally considered to be a relatively healthy and hardy breed. This study aimed to characterise the demography and common disorders of Border Terriers receiving veterinary care in England using de-identified electronic patient record data within the VetCompass™ Programme
The pseudogap: friend or foe of high Tc?
Although nineteen years have passed since the discovery of high temperature
superconductivity, there is still no consensus on its physical origin. This is
in large part because of a lack of understanding of the state of matter out of
which the superconductivity arises. In optimally and underdoped materials, this
state exhibits a pseudogap at temperatures large compared to the
superconducting transition temperature. Although discovered only three years
after the pioneering work of Bednorz and Muller, the physical origin of this
pseudogap behavior and whether it constitutes a distinct phase of matter is
still shrouded in mystery. In the summer of 2004, a band of physicists gathered
for five weeks at the Aspen Center for Physics to discuss the pseudogap. In
this perspective, we would like to summarize some of the results presented
there and discuss its importance in the context of strongly correlated electron
systems.Comment: expanded version, 20 pages, 11 figures, to be published, Advances in
Physic
A Fluorescence-Based High-Throughput Assay for the Discovery of Exchange Protein Directly Activated by Cyclic AMP (EPAC) Antagonists
Background: The discovery, more than ten years ago, of exchange proteins directly activated by cAMP (EPAC) as a new family of intracellular cAMP receptors revolutionized the cAMP signaling research field. Extensive studies have revealed that the cAMP signaling network is much more complex and dynamic as many cAMP-related cellular processes, previously thought to be controlled by protein kinase A, are found to be also mediated by EPAC proteins. Although there have been many important discoveries in the roles of EPACs greater understanding of their physiological function in cAMP-mediated signaling is impeded by the absence of EPAC-specific antagonist. Methodology/Principal Findings: To overcome this deficit, we have developed a fluorescence-based high throughput assay for screening EPAC specific antagonists. Our assay is highly reproducible and simple to perform using the ‘‘mix and measure’ ’ format. A pilot screening using the NCI-DTP diversity set library led to the identification of small chemical compounds capable of specifically inhibiting cAMP-induced EPAC activation while not affecting PKA activity. Conclusions/Significance: Our study establishes a robust high throughput screening assay that can be effectively applied for the discovery of EPAC-specific antagonists, which may provide valuable pharmacological tools for elucidating th
Mannose 6-Phosphate Receptor and Sortilin Mediated Endocytosis of α-Galactosidase A in Kidney Endothelial Cells
Prominent vasculopathy in Fabry disease patients is caused by excessive intracellular accumulation of globotriaosylceramide (GL-3) throughout the vascular endothelial cells causing progressive cerebrovascular, cardiac and renal impairments. The vascular lesions lead to myocardial ischemia, atherogenesis, stroke, aneurysm, thrombosis, and nephropathy. Hence, injury to the endothelial cells in the kidney is a key mechanism in human glomerular disease and endothelial cell repair is an important therapeutic target. We investigated the mechanism of uptake of α-galactosidase A (α-Gal A) in renal endothelial cells, in order to clarify if the recombinant enzyme is targeted to the lysosomes via the universal mannose 6-phosphate receptor (M6PR) and possibly other receptors. Immunohistochemical localization of infused recombinant α-Gal A in a renal biopsy from a classic Fabry disease patient showed that recombinant protein localize in the endothelial cells of the kidney. Affinity purification studies using α-Gal A resins identified M6PR and sortilin as α-Gal A receptors in cultured glomerular endothelial cells. Immunohistochemical analyses of normal human kidney with anti-sortilin and anti-M6PR showed that sortilin and M6PR were expressed in the endothelium of smaller and larger vessels. Uptake studies in cultured glomerular endothelial cells of α-Gal A labeled with fluorescence and 125I showed by inhibition with RAP and M6P that sortilin and M6PR mediated uptake of α-Gal A. Biacore studies revealed that α-Gal A binds to human M6PR with very high affinity, but M6PR also binds to sortilin in a way that prevents α-Gal A binding to sortilin. Taken together, our data provide evidence that sortilin is a new α-Gal A receptor expressed in renal endothelial cells and that this receptor together with the M6PR is able to internalize circulating α-Gal A during enzyme replacement therapy in patients with Fabry disease
Receptor-Mediated Endocytosis of α-Galactosidase A in Human Podocytes in Fabry Disease
Injury to the glomerular podocyte is a key mechanism in human glomerular disease and podocyte repair is an important therapeutic target. In Fabry disease, podocyte injury is caused by the intracellular accumulation of globotriaosylceramide. This study identifies in the human podocyte three endocytic receptors, mannose 6-phosphate/insulin-like growth II receptor, megalin, and sortilin and demonstrates their drug delivery capabilities for enzyme replacement therapy. Sortilin, a novel α-galactosidase A binding protein, reveals a predominant intracellular expression but also surface expression in the podocyte. The present study provides the rationale for the renal effect of treatment with α-galactosidase A and identifies potential pathways for future non-carbohydrate based drug delivery to the kidney podocyte and other potential affected organs
Ecosystem Overfishing in the Ocean
Fisheries catches represent a net export of mass and energy that can no longer be used by trophic levels higher than those fished. Thus, exploitation implies a depletion of secondary production of higher trophic levels (here the production of mass and energy by herbivores and carnivores in the ecosystem) due to the removal of prey. The depletion of secondary production due to the export of biomass and energy through catches was recently formulated as a proxy for evaluating the ecosystem impacts of fishing–i.e., the level of ecosystem overfishing. Here we evaluate the historical and current risk of ecosystem overfishing at a global scale by quantifying the depletion of secondary production using the best available fisheries and ecological data (i.e., catch and primary production). Our results highlight an increasing trend in the number of unsustainable fisheries (i.e., an increase in the risk of ecosystem overfishing) from the 1950s to the 2000s, and illustrate the worldwide geographic expansion of overfishing. These results enable to assess when and where fishing became unsustainable at the ecosystem level. At present, total catch per capita from Large Marine Ecosystems is at least twice the value estimated to ensure fishing at moderate sustainable levels
Stochastic Gravity: Theory and Applications
Whereas semiclassical gravity is based on the semiclassical Einstein equation
with sources given by the expectation value of the stress-energy tensor of
quantum fields, stochastic semiclassical gravity is based on the
Einstein-Langevin equation, which has in addition sources due to the noise
kernel. In the first part, we describe the fundamentals of this new theory via
two approaches: the axiomatic and the functional. In the second part, we
describe three applications of stochastic gravity theory. First, we consider
metric perturbations in a Minkowski spacetime, compute the two-point
correlation functions of these perturbations and prove that Minkowski spacetime
is a stable solution of semiclassical gravity. Second, we discuss structure
formation from the stochastic gravity viewpoint. Third, we discuss the
backreaction of Hawking radiation in the gravitational background of a black
hole and describe the metric fluctuations near the event horizon of an
evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews
in Relativity gr-qc/0307032 ; it includes new sections on the Validity of
Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric
Fluctuations of an Evaporating Black Hol
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