1,258 research outputs found

    Anomalous Fluctuations in Observations of Q0957+561 A,B: Smoking Gun of a Cosmic String?

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    We report the detection of anomalous brightness fluctuations in the multiple image Q0957+561 A,B gravitational lens system, and consider whether such anomalies have a plausible interpretation within the framework of cosmic string theory. We study a simple model of gravitational lensing by an asymmetrical rotating string. An explicit form of the lens equation is obtained and approximate relations for magnification are derived. We show that such a model with typical parameters of the GUT string can quantitatively reproduce the observed pattern of brightness fluctuations. On the other hand, explanation involving a binary star system as an alternative cause requires an unacceptably large massive object at a small distance. We also discuss possible observational manifestations of cosmic strings within our lens model.Comment: Published in Astronomy and Astrophysics. 7 pages, 6 figure

    Functional analysis of a missense mutation in the serine protease inhibitor SPINT2 associated with congenital sodium diarrhea.

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    Membrane-bound serine proteases play important roles in different biological processes. Their regulation by endogenous inhibitors is poorly understood. A Y163C mutation in the SPINT2 gene encoding the serine protease inhibitor Hepatocyte Growth Factor Inhibitor HAI-2 is associated with a congenital sodium diarrhea. The functional consequences of this mutation on HAI-2 activity and its physiological targets are unknown. We established a cellular assay in Xenopus laevis oocytes to study functional interactions between HAI-2 and candidate membrane-bound serine proteases expressed in the gastro-intestinal tract. We found that the wild-type form of HAI-2 is a potent inhibitor of nine gastro-intestinal serine proteases. The Y163C mutation in the second Kunitz domain of HAI-2 resulted in a complete loss of inhibitory activity on two intestinal proteases, prostasin and tmprss13. The effect of the mutation of the homologous Y68C in the first Kunitz domain of HAI-2 is consistent with a differential contribution of the two Kunitz domains of HAI-2 in the inhibition of serine proteases. By contrast to the Tyr to Cys, the Tyr to Ser substitution did not change the inhibitory potency of HAI-2, indicating that the thiol-group of the cysteine rather than the Tyr deletion is responsible for the HAI-2 loss of function. Our functional assay allowed us to identify membrane-bound serine proteases as cellular target for inhibition by HAI-2 wild type and mutants, and to better define the role of the Tyr in the second Kunitz domain in the inhibitory activity of HAI-2

    Proton and non-proton activation of ASIC channels.

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    The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when activated by pH values below 7.0. By contrast, non-proton ligands are able to trigger sustained ASIC currents at physiological pHs. To analyze the functional basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two distinct currents, a proton-induced desensitizing current and a sustained current triggered by sulfhydryl reagents. These currents differ in their pH dependency, their sensitivity to the sulfhydryl reagents, their ionic selectivity and their relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the channels can function in two distinct modes, a desensitizing mode and a sustained mode depending on the activating ligands. The pore vestibule of the channel represents a functional site for binding non-proton ligands to activate ASIC1 and ASIC2 at neutral pH and to prevent channel desensitization

    The Human Acid-Sensing Ion Channel ASIC1a: Evidence for a Homotetrameric Assembly State at the Cell Surface.

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    The chicken acid-sensing ion channel ASIC1 has been crystallized as a homotrimer. We address here the oligomeric state of the functional ASIC1 in situ at the cell surface. The oligomeric states of functional ASIC1a and mutants with additional cysteines introduced in the extracellular pore vestibule were resolved on SDS-PAGE. The functional ASIC1 complexes were stabilized at the cell surface of Xenopus laevis oocytes or CHO cells either using the sulfhydryl crosslinker BMOE, or sodium tetrathionate (NaTT). Under these different crosslinking conditions ASIC1a migrates as four distinct oligomeric states that correspond by mass to multiples of a single ASIC1a subunit. The relative importance of each of the four ASIC1a oligomers was critically dependent on the availability of cysteines in the transmembrane domain for crosslinking, consistent with the presence of ASIC1a homo-oligomers. The expression of ASIC1a monomers, trimeric or tetrameric concatemeric cDNA constructs resulted in functional channels. The resulting ASIC1a complexes are resolved as a predominant tetramer over the other oligomeric forms, after stabilization with BMOE or NaTT and SDS-PAGE/western blot analysis. Our data identify a major ASIC1a homotetramer at the surface membrane of the cell expressing functional ASIC1a channel

    Infrared Spectroscopy of GX 1+4/V2116 Oph: Evidence for a Fast Red Giant Wind?

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    We present infrared spectroscopy of the low-mass X-ray binary GX 1+4/V2116 Oph. This symbiotic binary consists of a 2-min accretion-powered pulsar and an M5 III red giant. A strong He I 1.083 micron emission line with a pronounced P Cygni profile was observed. From the blue edge of this feature, we infer an outflow velocity of 250(50) km/s. This is an order of magnitude faster than a typical red giant wind, and we suggest that radiation from the accretion disk or the neutron star may contribute to the acceleration of the outflow. We infer a wind mass loss rate of around 10^-6 Msun/yr. Accretion from such a strong stellar wind provides a plausible alternative to Roche lobe overflow for supplying the accretion disk which powers the X-ray source. The H I Paschen beta and He I 1.083 micron lines showed no evidence for the dramatic changes previously reported in some optical lines, and no evidence for pulsations at the 2-min pulsar period.Comment: 11 pages including 2 PS figures. To appear in ApJ Letter

    Hamiltonian Formulation of Two Body Problem in Wheeler-Feynman electrodynamics

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    A Hamiltonian formulation for the classical problem of electromagnetic interaction of two charged relativistic particles is found.Comment: 22 pages, 8 Uuencoded Postscript figure

    Quantifying suspended sediment concentration in subglacial sediment plumes discharging from two Svalbard tidewater glaciers using Landsat-8 and in situ measurements

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    This work was supported by National Science Foundation IGERT award: [Grant Number DGE-0801490]; National Science Foundation GK-12 award: [Grant Number DGE-0947790]; NASA supplement award: [Grant Number NNX10AG22G]; American Alpine Club under their Research Grant; Geological Society of America under their Research Grant; the ConocoPhillips-Ludin Northern Area Program under the CRIOS project (Calving Rates and Impact on Sea Level); and Dartmouth Earth Sciences Department.Marine-terminating outlet glaciers discharge mass through iceberg calving, submarine melting, and meltwater run-off. While calving can be quantified by in situ and remote-sensing observations, meltwater run-off, the subglacial transport of meltwater, and submarine melting are not well constrained due to inherent difficulties observing the subglacial and proglacial environments at tidewater glaciers. Remote-sensing and in situ measurements of surface sediment plumes, and their suspended sediment concentration (SSC), have been used as a proxy for glacier meltwater run-off. However, this relationship between satellite reflectance and SSC has predominantly been established using land-terminating glaciers. Here, we use two Svalbard tidewater glaciers to establish a well-constrained relationship between Landsat-8 surface reflecance and SSC and argue that it can be used to measure relative meltwater run-off at tidewater glaciers throughout a summer melt season. We find the highest correlation between SSCs and Landsat-8 surface reflectance by using the red + NIR band combination (r2 = 0.76). The highest correlation between SSCs and in situ field spectrometer measurements is in the 740-800 nm wavelength range (r2 = 0.85), a spectral range not currently measured by Landsat. Additionally, we find that in situ and Landsat-8 measurements for surface reflectance of SSCs are not interchangeable and therefore establish a relationship for each detection method. We then use the Landsat-8 relationship to calculate total surface sediment load, finding a strong correlation between total surface sediment load and a proxy for meltwater run-off (r2 ≥ 0.89). Our results establish a new metric to calculate SSCs from Landsat-8 surface reflectance and demonstrate how the SSC of subglacial sediment plumes can be used to monitor relative seasonal meltwater discharge at tidewater glaciers.Publisher PDFPeer reviewe

    Current Pathophysiological and Genetic Aspects of Dilated Cardiomyopathy

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    Dilated cardiomyopathy is the most common form of cardiomyopathy and the second leading cause of left ventricular dysfunction with highly variable clinical presentation and prognosis. The clinical courses vary and are strongly heterogeneous, ranging from asymptomatic patients to those suffering from intractable heart failure or sudden cardiac death due to arrhythmias. Previous studies have reported a 10 years cardiovascular mortality up to 40% in developed countries, due to advanced heart failure or sudden cardiac death. However, the prognosis of dilated cardiomyopathy patients is variable and depends on multiple risk factors. This chapter provides a review of dilated cardiomyopathy with specific focus on the pathophysiological aspects and genetic etiology of the disease
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