Influenza A virus infection and cigarette smoke impair bronchodilator responsiveness to β-adrenoceptor agonists in mouse lung.

β2-adrenoceptor agonists are the mainstay therapy for patients with asthma but their effectiveness in cigarette smoke (CS)-induced lung disease such as chronic obstructive pulmonary disease (COPD) is limited. In addition, bronchodilator efficacy of β2-adrenoceptor agonists is decreased during acute exacerbations of COPD (AECOPD), caused by respiratory viruses including influenza A. Therefore, the aim of the present study was to assess the effects of the β2-adrenoceptor agonist salbutamol (SALB) on small airway reactivity using mouse precision cut lung slices (PCLS) prepared from CS-exposed mice and from CS-exposed mice treated with influenza A virus (Mem71, H3N1). CS exposure alone reduced SALB potency and efficacy associated with decreased β2-adrenoceptor mRNA expression, and increased tumour necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression. This impaired relaxation was restored by day 12 in the absence of further CS exposure. In PCLS prepared after Mem71 infection alone, responses to SALB were transient and were not well maintained. CS exposure prior to Mem71 infection almost completely abolished relaxation, although β2-adrenoceptor and TNFα and IL-1β expression were unaltered. The present study has shown decreased sensitivity to SALB after CS or a combination of CS and Mem71 occurs by different mechanisms. In addition, the PCLS technique and our models of CS and influenza infection provide a novel setting for assessment of alternative bronchodilators

Particle acceleration

Data is compiled from Solar Maximum Mission and Hinothori satellites, particle detectors in several satellites, ground based instruments, and balloon flights in order to answer fundamental questions relating to: (1) the requirements for the coronal magnetic field structure in the vicinity of the energization source; (2) the height (above the photosphere) of the energization source; (3) the time of energization; (4) transistion between coronal heating and flares; (5) evidence for purely thermal, purely nonthermal and hybrid type flares; (6) the time characteristics of the energization source; (7) whether every flare accelerates protons; (8) the location of the interaction site of the ions and relativistic electrons; (9) the energy spectra for ions and relativistic electrons; (10) the relationship between particles at the Sun and interplanetary space; (11) evidence for more than one acceleration mechanism; (12) whether there is single mechanism that will accelerate particles to all energies and also heat the plasma; and (13) how fast the existing mechanisms accelerate electrons up to several MeV and ions to 1 GeV

Are Coronae of Magnetically Active Stars Heated by Flares? III. Analytical Distribution of Superimposed Flares

(abridged) We study the hypothesis that observed X-ray/extreme ultraviolet emission from coronae of magnetically active stars is entirely (or to a large part) due to the superposition of flares, using an analytic approach to determine the amplitude distribution of flares in light curves. The flare-heating hypothesis is motivated by time series that show continuous variability suggesting the presence of a large number of superimposed flares with similar rise and decay time scales. We rigorously relate the amplitude distribution of stellar flares to the observed histograms of binned counts and photon waiting times, under the assumption that the flares occur at random and have similar shapes. Applying these results to EUVE/DS observations of the flaring star AD Leo, we find that the flare amplitude distribution can be represented by a truncated power law with a power law index of 2.3 +/- 0.1. Our analytical results agree with existing Monte Carlo results of Kashyap et al. (2002) and Guedel et al. (2003). The method is applicable to a wide range of further stochastically bursting astrophysical sources such as cataclysmic variables, Gamma Ray Burst substructures, X-ray binaries, and spatially resolved observations of solar flares.Comment: accepted for publication in Ap

Local re-acceleration and a modified thick target model of solar flare electrons

The collisional thick target model (CTTM) of solar hard X-ray (HXR) bursts has become an almost 'Standard Model' of flare impulsive phase energy transport and radiation. However, it faces various problems in the light of recent data, particularly the high electron beam density and anisotropy it involves.} {We consider how photon yield per electron can be increased, and hence fast electron beam intensity requirements reduced, by local re-acceleration of fast electrons throughout the HXR source itself, after injection.} {We show parametrically that, if net re-acceleration rates due to e.g. waves or local current sheet electric (${\cal E}$) fields are a significant fraction of collisional loss rates, electron lifetimes, and hence the net radiative HXR output per electron can be substantially increased over the CTTM values. In this local re-acceleration thick target model (LRTTM) fast electron number requirements and anisotropy are thus reduced. One specific possible scenario involving such re-acceleration is discussed, viz, a current sheet cascade (CSC) in a randomly stressed magnetic loop.} {Combined MHD and test particle simulations show that local ${\cal E}$ fields in CSCs can efficiently accelerate electrons in the corona and and re-accelerate them after injection into the chromosphere. In this HXR source scenario, rapid synchronisation and variability of impulsive footpoint emissions can still occur since primary electron acceleration is in the high Alfv\'{e}n speed corona with fast re-acceleration in chromospheric CSCs. It is also consistent with the energy-dependent time-of-flight delays in HXR features.Comment: 8 pages, 2 figure

Gravito-magnetic instabilities in anisotropically expanding fluids

Gravitational instabilities in a magnetized Friedman - Robertson - Walker (FRW) Universe, in which the magnetic field was assumed to be too weak to destroy the isotropy of the model, are known and have been studied in the past. Accordingly, it became evident that the external magnetic field disfavors the perturbations' growth, suppressing the corresponding rate by an amount proportional to its strength. However, the spatial isotropy of the FRW Universe is not compatible with the presence of large-scale magnetic fields. Therefore, in this article we use the general-relativistic (GR) version of the (linearized) perturbed magnetohydrodynamic equations with and without resistivity, to discuss a generalized Jeans criterion and the potential formation of density condensations within a class of homogeneous and anisotropically expanding, self-gravitating, magnetized fluids in curved space-time. We find that, for a wide variety of anisotropic cosmological models, gravito-magnetic instabilities can lead to sub-horizonal, magnetized condensations. In the non-resistive case, the power spectrum of the unstable cosmological perturbations suggests that most of the power is concentrated on large scales (small k), very close to the horizon. On the other hand, in a resistive medium, the critical wave-numbers so obtained, exhibit a delicate dependence on resistivity, resulting in the reduction of the corresponding Jeans lengths to smaller scales (well bellow the horizon) than the non-resistive ones, while increasing the range of cosmological models which admit such an instability.Comment: 10 pages RevTex, 4 figures, accepted for publication in the International Journal of Modern Physics

Nox1 oxidase suppresses influenza a virus-induced lung inflammation and oxidative stress

Influenza A virus infection is an ongoing clinical problem and thus, there is an urgent need to understand the mechanisms that regulate the lung inflammation in order to unravel novel generic pharmacological strategies. Evidence indicates that the Nox2-containing NADPH oxidase enzyme promotes influenza A virus-induced lung oxidative stress, inflammation and dysfunction via ROS generation. In addition, lung epithelial and endothelial cells express the Nox1 isoform of NADPH oxidase, placing this enzyme at key sites to regulate influenza A virus-induced lung inflammation. The aim of this study was to investigate whether Nox1 oxidase regulates the inflammatory response and the oxidative stress to influenza infection in vivo in mice. Male WT and Nox1-deficient (Nox1−/y) mice were infected with the moderately pathogenic HkX-31 (H3N2, 1×104 PFU) influenza A virus for analysis of bodyweight, airways inflammation, oxidative stress, viral titre, lung histopathology, and cytokine/chemokine expression at 3 and 7 days post infection. HkX-31 virus infection of Nox1−/y mice resulted in significantly greater: loss of bodyweight (Day 3); BALF neutrophilia, peri-bronchial, peri-vascular and alveolar inflammation; Nox2-dependent inflammatory cell ROS production and peri-bronchial, epithelial and endothelial oxidative stress. The expression of pro-inflammatory cytokines including CCL2, CCL3, CXCL2, IL-1β, IL-6, GM-CSF and TNF-α was higher in Nox1−/y lungs compared to WT mice at Day 3, however, the expression of CCL2, CCL3, CXCL2, IFN-γ and the anti-inflammatory cytokine IL-10 were lower in lungs of Nox1−/y mice vs. WT mice at Day 7. Lung viral titre, and airways infiltration of active CD8+ and CD4+ T lymphocytes, and of Tregs were similar between WT and Nox1−/y mice. In conclusion, Nox1 oxidase suppresses influenza A virus induced lung inflammation and oxidative stress in mice particularly at the early phases of the infection. Nox1 and Nox2 oxidases appear to have opposing roles in the regulation of inflammation caused by influenza A viruses

Aspirin-triggered resolvin D1 reduces pneumococcal lung infection and inflammation in a viral and bacterial coinfection pneumonia model

Formyl peptide receptor 2/lipoxin A4 (LXA4) receptor (Fpr2/ALX) co-ordinates the transition from inflammation to resolution during acute infection by binding to distinct ligands including serum amyloid A (SAA) and Resolvin D1 (RvD1). Here, we evaluated the proresolving actions of aspirin-triggered RvD1 (AT-RvD1) in an acute coinfection pneumonia model. Coinfection with Streptococcus pneumoniae and influenza A virus (IAV) markedly increased pneumococcal lung load and neutrophilic inflammation during the resolution phase. Fpr2/ALX transcript levels were increased in the lungs of coinfected mice, and immunohistochemistry identified prominent Fpr2/ALX immunoreactivity in bronchial epithelial cells and macrophages. Levels of circulating and lung SAA were also highly increased in coinfected mice. Therapeutic treatment with exogenous AT-RvD1 during the acute phase of infection (day 4–6 post-pneumococcal inoculation) significantly reduced the pneumococcal load. AT-RvD1 also significantly reduced neutrophil elastase (NE) activity and restored total antimicrobial activity in bronchoalveolar lavage (BAL) fluid (BALF) of coinfected mice. Pneumonia severity, as measured by quantitating parenchymal inflammation or alveolitis was significantly reduced with AT-RvD1 treatment, which also reduced the number of infiltrating lung neutrophils and monocytes/macrophages as assessed by flow cytometry. The reduction in distal lung inflammation in AT-RvD1-treated mice was not associated with a significant reduction in inflammatory and chemokine mediators. In summary, we demonstrate that in the coinfection setting, SAA levels were persistently increased and exogenous AT-RvD1 facilitated more rapid clearance of pneumococci in the lungs, while concurrently reducing the severity of pneumonia by limiting excessive leukocyte chemotaxis from the infected bronchioles to distal areas of the lungs

Anomalous diffusion in a symbolic model

We address this work to investigate some statistical properties of symbolic sequences generated by a numerical procedure in which the symbols are repeated following a power law probability density. In this analysis, we consider that the sum of n symbols represents the position of a particle in erratic movement. This approach revealed a rich diffusive scenario characterized by non-Gaussian distributions and, depending on the power law exponent and also on the procedure used to build the walker, we may have superdiffusion, subdiffusion or usual diffusion. Additionally, we use the continuous-time random walk framework to compare with the numerical data, finding a good agreement. Because of its simplicity and flexibility, this model can be a candidate to describe real systems governed by power laws probabilities densities.Comment: Accepted for publication in Physica Script

Stochastic Cellular Automata Model for Stock Market Dynamics

In the present work we introduce a stochastic cellular automata model in order to simulate the dynamics of the stock market. A direct percolation method is used to create a hierarchy of clusters of active traders on a two dimensional grid. Active traders are characterised by the decision to buy, (+1), or sell, (-1), a stock at a certain discrete time step. The remaining cells are inactive,(0). The trading dynamics is then determined by the stochastic interaction between traders belonging to the same cluster. Most of the stylized aspects of the financial market time series are reproduced by the model.Comment: 17 pages and 7 figure

Magnetohydrodynamics and Plasma Cosmology

We study the linear magnetohydrodynamic (MHD) equations, both in the Newtonian and the general-relativistic limit, as regards a viscous magnetized fluid of finite conductivity and discuss instability criteria. In addition, we explore the excitation of cosmological perturbations in anisotropic spacetimes, in the presence of an ambient magnetic field. Acoustic, electromagnetic (e/m) and fast-magnetosonic modes, propagating normal to the magnetic field, can be excited, resulting in several implications of cosmological significance.Comment: 9 pages, RevTeX, To appear in the Proceedings of the Peyresq X Meeting, IJTP Conference Serie