253 research outputs found
Sensing and control in dual-recycling laser interferometer gravitational-wave detectors
We introduce length-sensing and control schemes for the dual-recycled cavity-enhanced Michelson interferometer configuration proposed for the Advanced Laser Interferometer Gravitational Wave Observatory (LIGO). We discuss the principles of this scheme and show methods that allow sensing and control signals to be derived. Experimental verification was carried out in three benchtop experiments that are introduced. We present the implications of the results from these experiments for Advanced LIGO and other future interferometric gravitational-wave detectors
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IL-1β Production through the NLRP3 Inflammasome by Hepatic Macrophages Links Hepatitis C Virus Infection with Liver Inflammation and Disease
Chronic hepatitis C virus (HCV) infection is a leading cause of liver disease. Liver inflammation underlies infection-induced fibrosis, cirrhosis and liver cancer but the processes that promote hepatic inflammation by HCV are not defined. We provide a systems biology analysis with multiple lines of evidence to indicate that interleukin-1β (IL-1β) production by intrahepatic macrophages confers liver inflammation through HCV-induced inflammasome signaling. Chronic hepatitis C patients exhibited elevated levels of serum IL-1β compared to healthy controls. Immunohistochemical analysis of healthy control and chronic hepatitis C liver sections revealed that Kupffer cells, resident hepatic macrophages, are the primary cellular source of hepatic IL-1β during HCV infection. Accordingly, we found that both blood monocyte-derived primary human macrophages, and Kupffer cells recovered from normal donor liver, produce IL-1β after HCV exposure. Using the THP-1 macrophage cell-culture model, we found that HCV drives a rapid but transient caspase-1 activation to stimulate IL-1β secretion. HCV can enter macrophages through non-CD81 mediated phagocytic uptake that is independent of productive infection. Viral RNA triggers MyD88-mediated TLR7 signaling to induce IL-1β mRNA expression. HCV uptake concomitantly induces a potassium efflux that activates the NLRP3 inflammasome for IL-1β processing and secretion. RNA sequencing analysis comparing THP1 cells and chronic hepatitis C patient liver demonstrates that viral engagement of the NLRP3 inflammasome stimulates IL-1β production to drive proinflammatory cytokine, chemokine, and immune-regulatory gene expression networks linked with HCV disease severity. These studies identify intrahepatic IL-1β production as a central feature of liver inflammation during HCV infection. Thus, strategies to suppress NLRP3 or IL-1β activity could offer therapeutic actions to reduce hepatic inflammation and mitigate disease
Dynamics of Wetting Fronts in Porous Media
We propose a new phenomenological approach for describing the dynamics of
wetting front propagation in porous media. Unlike traditional models, the
proposed approach is based on dynamic nature of the relation between capillary
pressure and medium saturation. We choose a modified phase-field model of
solidification as a particular case of such dynamic relation. We show that in
the traveling wave regime the results obtained from our approach reproduce
those derived from the standard model of flow in porous media. In more general
case, the proposed approach reveals the dependence of front dynamics upon the
flow regime.Comment: 4 pages, 2 figures, revte
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IFNL3 (IL28B) favorable genotype escapes hepatitis C virus-induced microRNAs and mRNA decay
The IFNL3 (IL28B) gene has received immense attention in the hepatitis C virus (HCV) field as multiple independent genome-wide association studies identified a strong association between polymorphisms near the IFNL3 gene and HCV clearance. However, the mechanism underlying this association has remained elusive. In this study, we report the identification of a functional polymorphism (rs4803217) located in the 3′ untranslated region (3′ UTR) of the IFNL3 mRNA that dictates transcript stability. This polymorphism influences AU-rich element-mediated decay as well as the binding of HCV-induced microRNAs during infection. Together, these pathways mediate robust repression of the unfavorable IFNL3 genotype. These data reveal a novel mechanism by which HCV attenuates the antiviral response and uncover new potential therapeutic targets for HCV treatment
Control of intestinal stem cell function and proliferation by mitochondrial pyruvate metabolism.
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation. Loss of the MPC in Lgr5-EGFP-positive stem cells, or treatment of intestinal organoids with an MPC inhibitor, increases proliferation and expands the stem cell compartment. Similarly, genetic deletion of the MPC in Drosophila intestinal stem cells also increases proliferation, whereas MPC overexpression suppresses stem cell proliferation. These data demonstrate that limiting mitochondrial pyruvate metabolism is necessary and sufficient to maintain the proliferation of intestinal stem cells
Stochastic Growth Equations and Reparametrization Invariance
It is shown that, by imposing reparametrization invariance, one may derive a
variety of stochastic equations describing the dynamics of surface growth and
identify the physical processes responsible for the various terms. This
approach provides a particularly transparent way to obtain continuum growth
equations for interfaces. It is straightforward to derive equations which
describe the coarse grained evolution of discrete lattice models and analyze
their small gradient expansion. In this way, the authors identify the basic
mechanisms which lead to the most commonly used growth equations. The
advantages of this formulation of growth processes is that it allows one to go
beyond the frequently used no-overhang approximation. The reparametrization
invariant form also displays explicitly the conservation laws for the specific
process and all the symmetries with respect to space-time transformations which
are usually lost in the small gradient expansion. Finally, it is observed, that
the knowledge of the full equation of motion, beyond the lowest order gradient
expansion, might be relevant in problems where the usual perturbative
renormalization methods fail.Comment: 42 pages, Revtex, no figures. To appear in Rev. of Mod. Phy
Searching for gravitational waves from known pulsars
We present upper limits on the amplitude of gravitational waves from 28
isolated pulsars using data from the second science run of LIGO. The results
are also expressed as a constraint on the pulsars' equatorial ellipticities. We
discuss a new way of presenting such ellipticity upper limits that takes
account of the uncertainties of the pulsar moment of inertia. We also extend
our previous method to search for known pulsars in binary systems, of which
there are about 80 in the sensitive frequency range of LIGO and GEO 600.Comment: Accepted by CQG for the proceeding of GWDAW9, 7 pages, 2 figure
Analysis of LIGO data for gravitational waves from binary neutron stars
We report on a search for gravitational waves from coalescing compact binary
systems in the Milky Way and the Magellanic Clouds. The analysis uses data
taken by two of the three LIGO interferometers during the first LIGO science
run and illustrates a method of setting upper limits on inspiral event rates
using interferometer data. The analysis pipeline is described with particular
attention to data selection and coincidence between the two interferometers. We
establish an observational upper limit of 1.7 \times 10^{2}M_\odot$.Comment: 17 pages, 9 figure
Setting upper limits on the strength of periodic gravitational waves from PSR J1939+2134 using the first science data from the GEO 600 and LIGO detectors
Data collected by the GEO 600 and LIGO interferometric gravitational wave detectors during their first observational science run were searched for continuous gravitational waves from the pulsar J1939+2134 at twice its rotation frequency. Two independent analysis methods were used and are demonstrated in this paper: a frequency domain method and a time domain method. Both achieve consistent null results, placing new upper limits on the strength of the pulsar's gravitational wave emission. A model emission mechanism is used to interpret the limits as a constraint on the pulsar's equatorial ellipticity
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