Nonlinear Rheology of Unentangled Polymer Melts Reinforced with High Concentration of Rigid Nanoparticles

A scaling model is presented to analyze the nonlinear rheology of unentangled polymer melts filled with high concentration of small spherical particles. Assuming the majority of chains to be reversibly adsorbed to the surface of the particles, we show that the emergence of nonlinearity in the viscoelastic response of the composite system subjected to a 2D shear flow results from stretching of the adsorbed chains and increasing desorption rate of the adsorbed segments due to the imposed deformation. The steady-state shear viscosity of the mixture in nonlinear shear thinning regime follows the power lawwhereis the applied shear rate. At large strain amplitude γ 0, the storage and loss moduli in strain sweep tests scale asandrespectively

The norovirus NS3 protein is a dynamic lipid- and microtubule-associated protein involved in viral RNA replication

Norovirus (NoV) infections are a significant health burden to society, yet the lack of reliable tissue culture systems has hampered the development of appropriate antiviral therapies. Here we show that the NoV NS3 protein, derived from murine NoV (MNV), is intimately associated with the MNV replication complex and the viral replication intermediate double-stranded RNA (dsRNA). We observed that when expressed individually, MNV NS3 and NS3 encoded by human Norwalk virus (NV) induced the formation of distinct vesicle-like structures that did not colocalize with any particular protein markers to cellular organelles but localized to cellular membranes, in particular those with a high cholesterol content. Both proteins also showed some degree of colocalization with the cytoskeleton marker β-tubulin. Although the distribution of MNV and NV NS3s were similar, NV NS3 displayed a higher level of colocalization with the Golgi apparatus and the endoplasmic reticulum (ER). However, we observed that although both proteins colocalized in membranes counterstained with filipin, an indicator of cholesterol content, MNV NS3 displayed a greater association with flotillin and stomatin, proteins known to associate with sphingolipid- and cholesterol-rich microdomains. Utilizing time-lapse epifluorescence microscopy, we observed that the membrane-derived vesicular structures induced by MNV NS3 were highly motile and dynamic in nature, and their movement was dependent on intact microtubules. These results begin to interrogate the functions of NoV proteins during virus replication and highlight the conserved properties of the NoV NS3 proteins among the seven Norovirus genogroups

Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection.

Norovirus infection is the leading cause of food-borne gastroenteritis worldwide, being responsible for over 200,000 deaths annually. Studies with murine norovirus (MNV) showed that protective STAT1 signaling controls viral replication and pathogenesis, but the immune mechanisms that noroviruses exploit to induce pathology are elusive. Here, we show that gastrointestinal MNV infection leads to widespread IL-1β maturation in MNV-susceptible STAT1-deficient mice. MNV activates the canonical Nlrp3 inflammasome in macrophages, leading to maturation of IL-1β and to Gasdermin D (GSDMD)-dependent pyroptosis. STAT1-deficient macrophages displayed increased MAVS-mediated expression of pro-IL-1β, facilitating elevated Nlrp3-dependent release of mature IL-1β upon MNV infection. Accordingly, MNV-infected Stat1-/- mice showed Nlrp3-dependent maturation of IL-1β as well as Nlrp3-dependent pyroptosis as assessed by in vivo cleavage of GSDMD to its active N-terminal fragment. While MNV-induced diarrheic responses were not affected, Stat1-/- mice additionally lacking either Nlrp3 or GSDMD displayed lower levels of the fecal inflammatory marker Lipocalin-2 as well as delayed lethality after gastrointestinal MNV infection. Together, these results uncover new insights into the mechanisms of norovirus-induced inflammation and cell death, thereby revealing Nlrp3 inflammasome activation and ensuing GSDMD-driven pyroptosis as contributors to MNV-induced immunopathology in susceptible STAT1-deficient mice.Wellcome Trust BBSR

Monte-Carlo Simulations of the Dynamical Behavior of the Coulomb Glass

We study the dynamical behavior of disordered many-particle systems with long-range Coulomb interactions by means of damage-spreading simulations. In this type of Monte-Carlo simulations one investigates the time evolution of the damage, i.e. the difference of the occupation numbers of two systems, subjected to the same thermal noise. We analyze the dependence of the damage on temperature and disorder strength. For zero disorder the spreading transition coincides with the equilibrium phase transition, whereas for finite disorder, we find evidence for a dynamical phase transition well below the transition temperature of the pure system.Comment: 10 pages RevTeX, 8 Postscript figure

The Density of States of hole-doped Manganites: A Scanning Tunneling Microscopy/Spectroscopy study

Variable temperature scanning tunneling microscopy/spectroscopy studies on single crystals and epitaxial thin films of hole-doped manganites, which show colossal magnetoresistance, have been done. We have investigated the variation of the density of states, at and near the Fermi energy ($E_f$), as a function of temperature. Simple calculations have been carried out, to find out the effect of temperature on the tunneling spectra and extract the variation of density of states with temperature, from the observed data. We also report here, atomic resolution images, on the single crystals and larger range images showing the growth patterns on thin films. Our investigation shows unambiguously that there is a rapid variation in density of states for temperatures near the Curie temperature ($T_c$). While for temperatures below $T_c$, a finite DOS is observed at $E_f$, for temperatures near $T_c$ a hard gap opens up in the density of states near $E_f$. For temperatures much higher than $T_c$, this gap most likely gives way to a soft gap. The observed hard gap for temperatures near $T_c$, is somewhat higher than the transport gap for all the materials. For different materials, we find that the magnitude of the hard gap decreases as the $T_c$ of the material increases and eventually, for materials with a $T_c$ close to 400 K, the value of the gap approaches zero.Comment: 9 pages RevTeX, 12 postscript figures, 1 table included in text, submitted to Physical Review

Sequence-dependent off-target inhibition of TLR7/8 sensing by synthetic microRNA inhibitors

Anti-microRNA (miRNA) oligonucleotides (AMOs) with 2\u27-O-Methyl (2\u27OMe) residues are commonly used to study miRNA function and can achieve high potency, with low cytotoxicity. Not withstanding this, we demonstrate the sequence-dependent capacity of 2\u27OMe AMOs to inhibit Toll-like receptor (TLR) 7 and 8 sensing of immunostimulatory RNA, independent of their miRNA-targeting function. Through a screen of 29 AMOs targeting common miRNAs, we found a subset of sequences highly inhibitory to TLR7 sensing in mouse macrophages. Interspecies conservation of this inhibitory activity was confirmed on TLR7/8 activity in human peripheral blood mononuclear cells. Significantly, we identified a core motif governing the inhibitory activity of these AMOs, which is present in more than 50 AMOs targeted to human miRNAs in miRBaseV20. DNA/locked nucleic acids (LNA) AMOs synthesized with a phosphorothioate backbone also inhibited TLR7 sensing in a sequence-dependent manner, demonstrating that the off-target effects of AMOs are not restricted to 2\u27OMe modification. Taken together, our work establishes the potential for off-target effects of AMOs on TLR7/8 function, which should be taken into account in their therapeutic development and in vivo application

1/f Noise in Electron Glasses

We show that 1/f noise is produced in a 3D electron glass by charge fluctuations due to electrons hopping between isolated sites and a percolating network at low temperatures. The low frequency noise spectrum goes as \omega^{-\alpha} with \alpha slightly larger than 1. This result together with the temperature dependence of \alpha and the noise amplitude are in good agreement with the recent experiments. These results hold true both with a flat, noninteracting density of states and with a density of states that includes Coulomb interactions. In the latter case, the density of states has a Coulomb gap that fills in with increasing temperature. For a large Coulomb gap width, this density of states gives a dc conductivity with a hopping exponent of approximately 0.75 which has been observed in recent experiments. For a small Coulomb gap width, the hopping exponent approximately 0.5.Comment: 8 pages, Latex, 6 encapsulated postscript figures, to be published in Phys. Rev.

Coulomb gap in a model with finite charge transfer energy

The Coulomb gap in a donor-acceptor model with finite charge transfer energy $\Delta$ describing the electronic system on the dielectric side of the metal-insulator transition is investigated by means of computer simulations on two- and three-dimensional finite samples with a random distribution of equal amounts of donor and acceptor sites. Rigorous relations reflecting the symmetry of the model presented with respect to the exchange of donors and acceptors are derived. In the immediate neighborhood of the Fermi energy $\mu$ the the density of one-electron excitations $g(\epsilon)$ is determined solely by finite size effects and $g(\epsilon)$ further away from $\mu$ is described by an asymmetric power law with a non-universal exponent, depending on the parameter $\Delta$.Comment: 10 pages, 6 figures, submitted to Phys. Rev.

Well dispersed fractal aggregates as filler in polymer-silica nanocomposites: long range effects in rheology

We are presenting a new method of processing polystyrene-silica nanocomposites, which results in a very well-defined dispersion of small primary aggregates (assembly of 15 nanoparticles of 10 nm diameter) in the matrix. The process is based on a high boiling point solvent, in which the nanoparticles are well dispersed, and controlled evaporation. The filler's fine network structure is determined over a wide range of sizes, using a combination of Small Angle Neutron Scattering (SANS) and Transmission Electronic Microscopy (TEM). The mechanical response of the nanocomposite material is investigated both for small (ARES oscillatory shear and Dynamical Mechanical Analysis) and large deformations (uniaxial traction), as a function of the concentration of the particles. We can investigate the structure-property correlations for the two main reinforcement effects: the filler network contribution, and a filler-polymer matrix effect. Above a silica volume fraction threshold, we see a divergence of the modulus correlated to the build up of a connected network. Below the threshold, we obtain a new additional elastic contribution of much longer terminal time than the matrix. Since aggregates are separated by at least 60 nm, this new filler-matrix contribution cannot be described solely with the concept of glassy layer (2nm)

Universal Crossover between Efros-Shklovskii and Mott Variable-Range-Hopping Regimes

A universal scaling function, describing the crossover between the Mott and the Efros-Shklovskii hopping regimes, is derived, using the percolation picture of transport in strongly localized systems. This function is agrees very well with experimental data. Quantitative comparison with experiment allows for the possible determination of the role played by polarons in the transport.Comment: 7 pages + 1 figure, Revte