The CAT Imaging Telescope for Very-High-Energy Gamma-Ray Astronomy

The CAT (Cherenkov Array at Themis) imaging telescope, equipped with a very-high-definition camera (546 fast phototubes with 0.12 degrees spacing surrounded by 54 larger tubes in two guard rings) started operation in Autumn 1996 on the site of the former solar plant Themis (France). Using the atmospheric Cherenkov technique, it detects and identifies very high energy gamma-rays in the range 250 GeV to a few tens of TeV. The instrument, which has detected three sources (Crab nebula, Mrk 421 and Mrk 501), is described in detail.Comment: 24 pages, 15 figures. submitted to Elsevier Preprin

Bird migration flight altitudes studied by a network of operational weather radars

A fully automated method for the detection and quantification of bird migration was developed for operational C-band weather radar, measuring bird density, speed and direction as a function of altitude. These weather radar bird observations have been validated with data from a high-accuracy dedicated bird radar, which was stationed in the measurement volume of weather radar sites in The Netherlands, Belgium and France for a full migration season during autumn 2007 and spring 2008. We show that weather radar can extract near real-time bird density altitude profiles that closely correspond to the density profiles measured by dedicated bird radar. Doppler weather radar can thus be used as a reliable sensor for quantifying bird densities aloft in an operational setting, which—when extended to multiple radars—enables the mapping and continuous monitoring of bird migration flyways. By applying the automated method to a network of weather radars, we observed how mesoscale variability in weather conditions structured the timing and altitude profile of bird migration within single nights. Bird density altitude profiles were observed that consisted of multiple layers, which could be explained from the distinct wind conditions at different take-off sites. Consistently lower bird densities are recorded in The Netherlands compared with sites in France and eastern Belgium, which reveals some of the spatial extent of the dominant Scandinavian flyway over continental Europe

Background Light in Potential Sites for the ANTARES Undersea Neutrino Telescope

The ANTARES collaboration has performed a series of {\em in situ} measurements to study the background light for a planned undersea neutrino telescope. Such background can be caused by $^{40}$K decays or by biological activity. We report on measurements at two sites in the Mediterranean Sea at depths of 2400~m and 2700~m, respectively. Three photomultiplier tubes were used to measure single counting rates and coincidence rates for pairs of tubes at various distances. The background rate is seen to consist of three components: a constant rate due to $^{40}$K decays, a continuum rate that varies on a time scale of several hours simultaneously over distances up to at least 40~m, and random bursts a few seconds long that are only correlated in time over distances of the order of a meter. A trigger requiring coincidences between nearby photomultiplier tubes should reduce the trigger rate for a neutrino telescope to a manageable level with only a small loss in efficiency.Comment: 18 pages, 8 figures, accepted for publication in Astroparticle Physic

Relation of exaggerated cytokine responses of CF airway epithelial cells to PAO1 adherence

In many model systems, cystic fibrosis (CF) phenotype airway epithelial cells in culture respond to P. aeruginosa with greater interleukin (IL)-8 and IL-6 secretion than matched controls. In order to test whether this excess inflammatory response results from the reported increased adherence of P. aeruginosa to the CF cells, we compared the inflammatory response of matched pairs of CF and non CF airway epithelial cell lines to the binding of GFP-PAO1, a strain of pseudomonas labeled with green fluorescent protein. There was no clear relation between GFP-PAO1 binding and cytokine production in response to PAO1. Treatment with exogenous aGM1 resulted in greater GFP-PAO1 binding to the normal phenotype compared to CF phenotype cells, but cytokine production remained greater from the CF cell lines. When cells were treated with neuraminidase, PAO1 adherence was equalized between CF and nonCF phenotype cell lines, but IL-8 production in response to inflammatory stimuli was still greater in CF phenotype cells. The polarized cell lines 16HBEo-Sense (normal phenotype) and Antisense (CF phenotype) cells were used to test the effect of disrupting tight junctions, which allows access of PAO1 to basolateral binding sites in both cell lines. IL-8 production increased from CF, but not normal, cells. These data indicate that increased bacterial binding to CF phenotype cells cannot by itself account for excess cytokine production in CF airway epithelial cells, encourage investigation of alternative hypotheses, and signal caution for therapeutic strategies proposed for CF that include disruption of tight junctions in the face of pseudomonas infection

Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice

Objective and designCystic fibrosis transmembrane conductance regulator (CFTR) regulates infection and inflammation. In this study, we investigated whether a lack of functional CFTR in neutrophils would promote lipopolysaccharide (LPS)-induced lung inflammation and injury.Materials and methodsCFTR-inhibited or F508del-CFTR-mutated neutrophils were stimulated with LPS and cultured to evaluate production of cytokines and NF-κB activation. Wild-type mice were reconstituted with F508del neutrophils or bone marrow and then intratracheally challenged with LPS to observe lung inflammatory response.ResultsPharmacologic inhibition and genetic mutation of CFTR in neutrophils activated NF-κB and facilitated macrophage inflammatory protein-2 (MIP-2) and tumor necrosis factor-α (TNF-α) production. Wild-type mice reconstituted with F508del neutrophils and bone marrow had more severe lung inflammation and injury after LPS challenge compared to wild-type mice receiving wild-type neutrophils or bone marrow reconstitution.ConclusionsLack of functional CFTR in neutrophils can promote LPS-induced acute lung inflammation and injury

The effect of forearm posture on wrist flexion in computer workers with chronic upper extremity musculoskeletal disorders

<p>Abstract</p> <p>Background</p> <p>Occupational computer use has been associated with upper extremity musculoskeletal disorders (UEMSDs), but the etiology and pathophysiology of some of these disorders are poorly understood. Various theories attribute the symptoms to biomechanical and/or psychosocial stressors. The results of several clinical studies suggest that elevated antagonist muscle tension may be a biomechanical stress factor. Affected computer users often exhibit limited wrist range of motion, particularly wrist flexion, which has been attributed to increased extensor muscle tension, rather than to pain symptoms. Recreational or domestic activities requiring extremes of wrist flexion may produce injurious stress on the wrist joint and muscles, the symptoms of which are then exacerbated by computer use. As these activities may involve a variety of forearm postures, we examined whether changes in forearm posture have an effect on pain reports during wrist flexion, or whether pain would have a limiting effect on flexion angle.</p> <p>Methods</p> <p>We measured maximum active wrist flexion using a goniometer with the forearm supported in the prone, neutral, and supine postures. Data was obtained from 5 subjects with UEMSDs attributed to computer use and from 13 control subjects.</p> <p>Results</p> <p>The UEMSD group exhibited significantly restricted wrist flexion compared to the control group in both wrists at all forearm postures with the exception of the non-dominant wrist with the forearm prone. In both groups, maximum active wrist flexion decreased at the supine forearm posture compared to the prone posture. No UEMSD subjects reported an increase in pain symptoms during testing.</p> <p>Conclusion</p> <p>The UEMSD group exhibited reduced wrist flexion compared to controls that did not appear to be pain related. A supine forearm posture reduced wrist flexion in both groups, but the reduction was approximately 100% greater in the UEMSD group. The effect of a supine forearm posture on wrist flexion is consistent with known biomechanical changes in the distal extensor carpi ulnaris tendon that occur with forearm supination. We infer from these results that wrist extensor muscle passive tension may be elevated in UEMSD subjects compared to controls, particularly in the extensor carpi ulnaris muscle. Measuring wrist flexion at the supine forearm posture may highlight flexion restrictions that are not otherwise apparent.</p

The effects of interleukin-8 on airway smooth muscle contraction in cystic fibrosis

<p>Abstract</p> <p>Background</p> <p>Many cystic fibrosis (CF) patients display airway hyperresponsiveness and have symptoms of asthma such as cough, wheezing and reversible airway obstruction. Chronic airway bacterial colonization, associated with neutrophilic inflammation and high levels of interleukin-8 (IL-8) is also a common occurrence in these patients. The aim of this work was to determine the responsiveness of airway smooth muscle to IL-8 in CF patients compared to non-CF individuals.</p> <p>Methods</p> <p>Experiments were conducted on cultured ASM cells harvested from subjects with and without CF (control subjects). Cells from the 2^ndto 5^thpassage were studied. Expression of the IL-8 receptors CXCR1 and CXCR2 was assessed by flow cytometry. The cell response to IL-8 was determined by measuring intracellular calcium concentration ([Ca²⁺]_i), cell contraction, migration and proliferation.</p> <p>Results</p> <p>The IL-8 receptors CXCR1 and CXCR2 were expressed in both non-CF and CF ASM cells to a comparable extent. IL-8 (100 nM) induced a peak Ca²⁺release that was higher in control than in CF cells: 228 ± 7 versus 198 ± 10 nM (p < 0.05). IL-8 induced contraction was greater in CF cells compared to control. Furthermore, IL-8 exposure resulted in greater phosphorylation of myosin light chain (MLC₂₀) in CF than in control cells. In addition, MLC₂₀expression was also increased in CF cells. Exposure to IL-8 induced migration and proliferation of both groups of ASM cells but was not different between CF and non-CF cells.</p> <p>Conclusion</p> <p>ASM cells of CF patients are more contractile to IL-8 than non-CF ASM cells. This enhanced contractility may be due to an increase in the amount of contractile protein MLC₂₀. Higher expression of MLC₂₀by CF cells could contribute to airway hyperresponsiveness to IL-8 in CF patients.</p

Azithromycin reduces spontaneous and induced inflammation in ΔF508 cystic fibrosis mice

BACKGROUND: Inflammation plays a critical role in lung disease development and progression in cystic fibrosis. Azithromycin is used for the treatment of cystic fibrosis lung disease, although its mechanisms of action are poorly understood. We tested the hypothesis that azithromycin modulates lung inflammation in cystic fibrosis mice. METHODS: We monitored cellular and molecular inflammatory markers in lungs of cystic fibrosis mutant mice homozygous for the ΔF508 mutation and their littermate controls, either in baseline conditions or after induction of acute inflammation by intratracheal instillation of lipopolysaccharide from Pseudomonas aeruginosa, which would be independent of interactions of bacteria with epithelial cells. The effect of azithromycin pretreatment (10 mg/kg/day) given by oral administration for 4 weeks was evaluated. RESULTS: In naive cystic fibrosis mice, a spontaneous lung inflammation was observed, characterized by macrophage and neutrophil infiltration, and increased intra-luminal content of the pro-inflammatory cytokine macrophage inflammatory protein-2. After induced inflammation, cystic fibrosis mice combined exaggerated cellular infiltration and lower anti-inflammatory interleukin-10 production. In cystic fibrosis mice, azithromycin attenuated cellular infiltration in both baseline and induced inflammatory condition, and inhibited cytokine (tumor necrosis factor-α and macrophage inflammatory protein-2) release in lipopolysaccharide-induced inflammation. CONCLUSION: Our findings further support the concept that inflammatory responses are upregulated in cystic fibrosis. Azithromycin reduces some lung inflammation outcome measures in cystic fibrosis mice. We postulate that some of the benefits of azithromycin treatment in cystic fibrosis patients are due to modulation of lung inflammation

DNA demethylation-dependent enhancement of toll-like receptor-2 gene expression in cystic fibrosis epithelial cells involves SP1-activated transcription

<p>Abstract</p> <p>Background</p> <p>The clinical course of cystic fibrosis (CF) is characterized by recurrent pulmonary infections and chronic inflammation. We have recently shown that decreased methylation of the toll-like receptor-2 (TLR2) promoter leads to an apparent CF-related up-regulation of TLR2. This up-regulation could be responsible, in part, for the CF-associated enhanced proinflammatory responses to various bacterial products in epithelial cells. However, the molecular mechanisms underlying DNA hypomethylation-dependent enhancement of TLR2 expression in CF cells remain unknown.</p> <p>Results</p> <p>The present study indicates that there is a specific CpG region (CpG#18-20), adjacent to the SP1 binding site that is significantly hypomethylated in several CF epithelial cell lines. These CpGs encompass a minimal promoter region required for basal TLR2 expression, and suggests that CpG#18-20 methylation regulates TLR2 expression in epithelial cells. Furthermore, reporter gene analysis indicated that the SP1 binding site is involved in the methylation-dependent regulation of the TLR2 promoter. Inhibition of SP1 with mithramycin A decreased TLR2 expression in both CF and 5-azacytidine-treated non-CF epithelial cells. Moreover, even though SP1 binding was not affected by CpG methylation, SP1-dependent transcription was abolished by CpG methylation.</p> <p>Conclusion</p> <p>This report implicates SP1 as a critical component of DNA demethylation-dependent up-regulation of TLR2 expression in CF epithelial cells.</p