6,350 research outputs found
Chapman-Enskog expansion about nonequilibrium states: the sheared granular fluid
The Chapman-Enskog method of solution of kinetic equations, such as the
Boltzmann equation, is based on an expansion in gradients of the deviations fo
the hydrodynamic fields from a uniform reference state (e.g., local
equilibrium). This paper presents an extension of the method so as to allow for
expansions about \emph{arbitrary}, far-from equilibrium reference states. The
primary result is a set of hydrodynamic equations for studying variations from
the arbitrary reference state which, unlike the usual Navier-Stokes
hydrodynamics, does not restrict the reference state in any way. The method is
illustrated by application to a sheared granular gas which cannot be studied
using the usual Navier-Stokes hydrodynamics.Comment: 23 pages, no figures. Submited to PRE Replaced to correct misc.
errors Replaced to correct misc. errors, make notation more consistant,
extend discussio
Field-test of a robust, portable, frequency-stable laser
We operate a frequency-stable laser in a non-laboratory environment where the
test platform is a passenger vehicle. We measure the acceleration experienced
by the laser and actively correct for it to achieve a system acceleration
sensitivity of = /g, /g, and /g for accelerations in three orthogonal
directions at 1 Hz. The acceleration spectrum and laser performance are
evaluated with the vehicle both stationary and moving. The laser linewidth in
the stationary vehicle with engine idling is 1.7(1) Hz
Proton Association Constants of His 37 in the Influenza-A M218–60 Dimer-of-Dimers
National Institute of Biomedical Imaging and Bioengineering (U.S.) (EB001960)National Institute of Biomedical Imaging and Bioengineering (U.S.) (EB002026)National Institute of Biomedical Imaging and Bioengineering (U.S.) (GM094648
LP340, a novel histone deacetylase inhibitor, decreases liver injury and fibrosis in mice: role of oxidative stress and microRNA-23a
Effective therapy for liver fibrosis is lacking. Here, we examined whether LP340, the lead candidate of a new-generation of hydrazide-based HDAC1,2,3 inhibitors (HDACi), decreases liver fibrosis. Liver fibrosis was induced by CCl4 treatment and bile duct ligation (BDL) in mice. At 6 weeks after CCl4, serum alanine aminotransferase increased, and necrotic cell death and leukocyte infiltration occurred in the liver. Tumor necrosis factor-α and myeloperoxidase markedly increased, indicating inflammation. After 6 weeks, α-smooth muscle actin (αSMA) and collagen-1 expression increased by 80% and 575%, respectively, indicating hepatic stellate cell (HSC) activation and fibrogenesis. Fibrosis detected by trichrome and Sirius-red staining occurred primarily in pericentral regions with some bridging fibrosis in liver sections. 4-Hydroxynonenal adducts (indicator of oxidative stress), profibrotic cytokine transforming growth factor-β (TGFβ), and TGFβ downstream signaling molecules phospho-Smad2/3 also markedly increased. LP340 attenuated indices of liver injury, inflammation, and fibrosis markedly. Moreover, Ski-related novel protein-N (SnoN), an endogenous inhibitor of TGFβ signaling, decreased, whereas SnoN expression suppressor microRNA-23a (miR23a) increased markedly. LP340 (0.05 mg/kg, ig., daily during the last 2 weeks of CCl4 treatment) decreased 4-hydroxynonenal adducts and miR23a production, blunted SnoN decreases, and inhibited the TGFβ/Smad signaling. By contrast, LP340 had no effect on matrix metalloproteinase-9 expression. LP340 increased histone-3 acetylation but not tubulin acetylation, indicating that LP340 inhibited Class-I but not Class-II HDAC in vivo. After BDL, focal necrosis, inflammation, ductular reactions, and portal and bridging fibrosis occurred at 2 weeks, and αSMA and collagen-1 expression increased by 256% and 560%, respectively. LP340 attenuated liver injury, ductular reactions, inflammation, and liver fibrosis. LP340 also decreased 4-hydroxynonenal adducts and miR23a production, prevented SnoN decreases, and inhibited the TGFβ/Smad signaling after BDL. In vitro, LP340 inhibited immortal human hepatic stellate cells (hTERT-HSC) activation in culture (αSMA and collagen-1 expression) as well as miR23a production, demonstrating its direct inhibitory effects on HSC. In conclusions, LP340 is a promising therapy for both portal and pericentral liver fibrosis, and it works by inhibiting oxidative stress and decreasing miR23a
Inherent Rheology of a Granular Fluid in Uniform Shear Flow
In contrast to normal fluids, a granular fluid under shear supports a steady
state with uniform temperature and density since the collisional cooling can
compensate locally for viscous heating. It is shown that the hydrodynamic
description of this steady state is inherently non-Newtonian. As a consequence,
the Newtonian shear viscosity cannot be determined from experiments or
simulation of uniform shear flow. For a given degree of inelasticity, the
complete nonlinear dependence of the shear viscosity on the shear rate requires
the analysis of the unsteady hydrodynamic behavior. The relationship to the
Chapman-Enskog method to derive hydrodynamics is clarified using an approximate
Grad's solution of the Boltzmann kinetic equationComment: 10 pages, 4 figures; substantially enlarged version; to be published
in PR
Unusual architecture of the p7 channel from hepatitis C virus
The Hepatitis C virus (HCV) has developed a small membrane protein, p7, which remarkably can self-assemble into a large channel complex that selectively conducts cations1-4. We are curious as to what structural solution has the viroporin adopted to afford selective cation conduction because p7 has no homology with any of the known prokaryotic or eukaryotic channel proteins. The p7 activity can be inhibited by amantadine and rimantadine2,5, which also happen to be potent blockers of the influenza M2 channel6 and licensed drugs against influenza infections7. The adamantane derivatives were subjects of HCV clinical trials8, but large variation in drug efficacy among the various HCV genotypes has been difficult to explain without detailed molecular structures. Here, we determined the structures of this HCV viroporin as well as its drug-binding site using the latest nuclear magnetic resonance (NMR) technologies. The structure exhibits an unusual mode of hexameric assembly, where the individual p7 monomers, i, not only interact with their immediate neighbors, but also reach farther to associate with the i+2 and i+3 monomers, forming a sophisticated, funnel-like architecture. The structure also alludes to a mechanism of cation selection: an asparagine/histidine ring that constricts the narrow end of the funnel serves as a broad cation selectivity filter while an arginine/lysine ring that defines the wide end of the funnel may selectively allow cation diffusion into the channel. Our functional investigation using whole-cell channel recording showed that these residues are indeed critical for channel activity. NMR measurements of the channel-drug complex revealed six equivalent hydrophobic pockets between the peripheral and pore-forming helices to which amantadine or rimantadine binds, and compound binding specifically to this position may allosterically inhibit cation conduction by preventing the channel from opening. Our data provide molecular explanation for p7-mediated cation conductance and its inhibition by adamantane derivatives
Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)
The Rosetta molecular modeling software package provides experimentally
tested and rapidly evolving tools for the 3D structure prediction and
high-resolution design of proteins, nucleic acids, and a growing number of
non-natural polymers. Despite its free availability to academic users and
improving documentation, use of Rosetta has largely remained confined to
developers and their immediate collaborators due to the code's difficulty of
use, the requirement for large computational resources, and the unavailability
of servers for most of the Rosetta applications. Here, we present a unified web
framework for Rosetta applications called ROSIE (Rosetta Online Server that
Includes Everyone). ROSIE provides (a) a common user interface for Rosetta
protocols, (b) a stable application programming interface for developers to add
additional protocols, (c) a flexible back-end to allow leveraging of computer
cluster resources shared by RosettaCommons member institutions, and (d)
centralized administration by the RosettaCommons to ensure continuous
maintenance. This paper describes the ROSIE server infrastructure, a
step-by-step 'serverification' protocol for use by Rosetta developers, and the
deployment of the first nine ROSIE applications by six separate developer
teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance,
Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated
by the number and diversity of these applications, ROSIE offers a general and
speedy paradigm for serverification of Rosetta applications that incurs
negligible cost to developers and lowers barriers to Rosetta use for the
broader biological community. ROSIE is available at
http://rosie.rosettacommons.org
In-situ strain tuning of the Dirac surface states in Bi2Se3 films
Elastic strain has the potential for a controlled manipulation of the band
gap and spin-polarized Dirac states of topological materials, which can lead to
pseudo-magnetic-field effects, helical flat bands and topological phase
transitions. However, practical realization of these exotic phenomena is
challenging and yet to be achieved. Here, we show that the Dirac surface states
of the topological insulator Bi2Se3 can be reversibly tuned by an externally
applied elastic strain. Performing in-situ x-ray diffraction and in-situ
angle-resolved photoemission spectroscopy measurements during tensile testing
of epitaxial Bi2Se3 films bonded onto a flexible substrate, we demonstrate
elastic strains of up to 2.1% and quantify the resulting reversible changes in
the topological surface state. Our study establishes the functional
relationship between the lattice and electronic structures of Bi2Se3 and, more
generally, demonstrates a new route toward momentum-resolved mapping of
strain-induced band structure changes
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