Requirement for chloride channel function during the hepatitis C virus life cycle

Hepatocytes express an array of plasma membrane and intracellular ion channels, yet their role during the hepatitis C virus (HCV) life cycle remains largely undefined. Here, we show that HCV increases intracellular hepatic chloride (Cl-) influx that can be inhibited by selective Cl- channel blockers. Through pharmacological and small interfering RNA (siRNA)-mediated silencing, we demonstrate that Cl- channel inhibition is detrimental to HCV replication. This represents the first observation of the involvement of Cl- channels during the HCV life cycle

Critical behaviour in parabolic geometries

We study two-dimensional systems with boundary curves described by power laws. Using conformal mappings we obtain the correlations at the bulk critical point. Three different classes of behaviour are found and explained by scaling arguments which also apply to higher dimensions. For an Ising system of parabolic shape the behaviour of the order at the tip is also found.Comment: Old paper, for archiving. 6 pages, 1 figure, epsf, IOP macr

Dynamics and transport in random quantum systems governed by strong-randomness fixed points

We present results on the low-frequency dynamical and transport properties of random quantum systems whose low temperature ($T$), low-energy behavior is controlled by strong disorder fixed points. We obtain the momentum and frequency dependent dynamic structure factor in the Random Singlet (RS) phases of both spin-1/2 and spin-1 random antiferromagnetic chains, as well as in the Random Dimer (RD) and Ising Antiferromagnetic (IAF) phases of spin-1/2 random antiferromagnetic chains. We show that the RS phases are unusual `spin metals' with divergent low-frequency spin conductivity at T=0, and we also follow the conductivity through novel `metal-insulator' transitions tuned by the strength of dimerization or Ising anisotropy in the spin-1/2 case, and by the strength of disorder in the spin-1 case. We work out the average spin and energy autocorrelations in the one-dimensional random transverse field Ising model in the vicinity of its quantum critical point. All of the above calculations are valid in the frequency dominated regime \omega \agt T, and rely on previously available renormalization group schemes that describe these systems in terms of the properties of certain strong-disorder fixed point theories. In addition, we obtain some information about the behavior of the dynamic structure factor and dynamical conductivity in the opposite `hydrodynamic' regime $\omega < T$ for the special case of spin-1/2 chains close to the planar limit (the quantum x-y model) by analyzing the corresponding quantities in an equivalent model of spinless fermions with weak repulsive interactions and particle-hole symmetric disorder.Comment: Long version (with many additional results) of Phys. Rev. Lett. {\bf 84}, 3434 (2000) (available as cond-mat/9904290); two-column format, 33 pages and 8 figure

Radial Fredholm perturbation in the two-dimensional Ising model and gap-exponent relation

We consider concentric circular defects in the two-dimensional Ising model, which are distributed according to a generalized Fredholm sequence, i. e. at exponentially increasing radii. This type of aperiodicity does not change the bulk critical behaviour but introduces a marginal extended perturbation. The critical exponent of the local magnetization is obtained through finite-size scaling, using a corner transfer matrix approach in the extreme anisotropic limit. It varies continuously with the amplitude of the modulation and is closely related to the magnetic exponent of the radial Hilhorst-van Leeuwen model. Through a conformal mapping of the system onto a strip, the gap-exponent relation is shown to remain valid for such an aperiodic defect.Comment: 12 pages, TeX file + 4 figures, epsf neede

Quantum Quench from a Thermal Initial State

We consider a quantum quench in a system of free bosons, starting from a thermal initial state. As in the case where the system is initially in the ground state, any finite subsystem eventually reaches a stationary thermal state with a momentum-dependent effective temperature. We find that this can, in some cases, even be lower than the initial temperature. We also study lattice effects and discuss more general types of quenches.Comment: 6 pages, 2 figures; short published version, added references, minor change

Regularity Properties and Pathologies of Position-Space Renormalization-Group Transformations

We reconsider the conceptual foundations of the renormalization-group (RG) formalism, and prove some rigorous theorems on the regularity properties and possible pathologies of the RG map. Regarding regularity, we show that the RG map, defined on a suitable space of interactions (= formal Hamiltonians), is always single-valued and Lipschitz continuous on its domain of definition. This rules out a recently proposed scenario for the RG description of first-order phase transitions. On the pathological side, we make rigorous some arguments of Griffiths, Pearce and Israel, and prove in several cases that the renormalized measure is not a Gibbs measure for any reasonable interaction. This means that the RG map is ill-defined, and that the conventional RG description of first-order phase transitions is not universally valid. For decimation or Kadanoff transformations applied to the Ising model in dimension $d \ge 3$, these pathologies occur in a full neighborhood $\{ \beta > \beta_0 ,\, |h| < \epsilon(\beta) \}$ of the low-temperature part of the first-order phase-transition surface. For block-averaging transformations applied to the Ising model in dimension $d \ge 2$, the pathologies occur at low temperatures for arbitrary magnetic-field strength. Pathologies may also occur in the critical region for Ising models in dimension $d \ge 4$. We discuss in detail the distinction between Gibbsian and non-Gibbsian measures, and give a rather complete catalogue of the known examples. Finally, we discuss the heuristic and numerical evidence on RG pathologies in the light of our rigorous theorems.Comment: 273 pages including 14 figures, Postscript, See also ftp.scri.fsu.edu:hep-lat/papers/9210/9210032.ps.

An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications

Natural compounds isolated from Brazilian plants are potent inhibitors of hepatitis C virus replication in vitro

Compounds extracted from plants can provide an alternative approach to new therapies. They present characteristics such as high chemical diversity, lower cost of production and milder or inexistent side effects compared with conventional treatment. The Brazilian flora represents a vast, largely untapped, resource of potential antiviral compounds. In this study, we investigate the antiviral effects of a panel of natural compounds isolated from Brazilian plants species on hepatitis C virus (HCV) genome replication. To do this we used firefly luciferase-based HCV sub-genomic replicons of genotypes 2a (JFH-1), 1b and 3a and the compounds were assessed for their effects on both HCV replication and cellular toxicity. Initial screening of compounds was performed using the maximum non-toxic concentration and 4 compounds that exhibited a useful therapeutic index (favourable ratio of cytotoxicity to antiviral potency) were selected for extra analysis. The compounds APS (EC50 = 2.3 μM), a natural alkaloid isolated from Maytrenus ilicifolia, and the lignans 3∗43 (EC50 = 4.0 μM), 3∗20 (EC50 = 8.2 μM) and 5∗362 (EC50 = 38.9 μM) from Peperomia blanda dramatically inhibited HCV replication as judged by reductions in luciferase activity and HCV protein expression in both the subgenomic and infectious systems. We further show that these compounds are active against a daclatasvir resistance mutant subgenomic replicon. Consistent with inhibition of genome replication, production of infectious JFH-1 virus was significantly reduced by all 4 compounds. These data are the first description of Brazilian natural compounds possessing anti-HCV activity and further analyses are being performed in order to investigate the mode of action of those compounds