Cytokine gene transfer by adenoviral vectors as a novel therapeutic option for hepatitis B virus infection

Hepatitis B virus (HBV) is a hepatotropic, non-cytopathic DNA virus that causes acute and chronic necroinflammatory liver disease and hepatocellular carcinoma. It has been shown that HBV DNA replication is suppressed by interferon (IFN) a/b, IFNg and other cytokines. The aim of my thesis was to establish a liver directed gene transfer and to characterize the effect of local expression of interferon on HBV replication. Two sets of adenoviral vectors were established: the first using the CMV promoter (PCMV) (AdmIFNg and AdmIFNb) and the second using a bidirectional tetracycline (tet)-regulated promoter(Pbi-1) (Adbiluc vectors) to locally express mouse interferon (mIFN) a, b and g. In mouse hepatocyte cultures, a 5- to 10-fold decrease of intracellular HBV DNA was observed following infection with AdmIFNb or AdmIFNg. The antiviral effect was enhanced in HBV transgenic mice where 95% of intrahepatic and serum HBV DNA disappeared 2 weeks after intravenous injection. However, the effect was transient and HBV replication was restored. This was partially due to a down regulation of the CMV promoter. Using the Adbiluc vectors, expression of the reverse tet-transactivator (rtTA) under liver specific promoters (e.g. in transgenic mice or with a second vector) ensured tissue specificity of gene expression. Co-expression of luciferase with the bidirectional promoter Pbi-1 allowed monitoring. Simultaneous, strong expression of both genes dependent on the dose of tetracycline in vitro and tight regulation in living mice were shown. However, in one direction, gene expression was slightly leaky. This was exploited to avoid separate expression of the tet-transactivator: rtTA was cloned under control of Pbi-1 to establish a tet-regulated one-vector system. Using the Adbiluc-IFN vectors, rapid induction of cytokine expression in the livers of transduced mice was fatal, but moderate expression was well tolerated. Due to these difficulties in the first experiments in mouse models for chronic and acute HBV infection, the antiviral effect of regulated IFN-expression could not yet be demonstrated. Taken together, local expression of cytokines was successfully established following adenoviral gene transfer and an antiviral effect was demonstrated. A set of novel adenoviral vector allowing tet-regulated and monitored cytokine expression will allow characterizing the antiviral pathways. This approach can also be used to develop gene therapy of chronic HBV and hepatitis C virus infection and other diseases like malaria or liver cancer

Tests on a mock-up of the feedback controlled matching options for the ITER ICRH system

For the ICRH of ITER 20MW must be coupled to the plasma in the 40-55MHz frequency band via an array of 24 radiating shorted straps fed by four generators. The matching system must provide automatic matching control on the mean load provided by the plasma and be resilient (|Γ| < 0.2) to a wide range of fast antenna load excursions occurring in ELMy plasmas. Furthermore, good control of the current distribution in the strap array must be possible for the various heating and current drive scenarios. Two load resilient matching options have been considered for ITER: the 4 “Conjugate-T” (CT) and the 4 hybrids ones, the first being presently considered as a back-up option. Automatic control of these 2 options is presently developed, and tested for optimization on a low-powered scaled mock-up. Successful implementation of the simultaneous feedback control of 11 actuators for the matching of the 4CT and for the control of the toroidal phasing has already been achieved. The matching and the array current control of the 3dB hybrid option is provided by simultaneous feedback control of the decouplers and double stub tuners (in total 23 actuators) and is being progressively implemented. The simultaneous control of matching and antenna current has already been successfully tested on part of the array

Effect of point source emission height on the error of the flux estimation through eddy covariance

A challenge commonly associated with eddy covariance is that real measurement sites are rarely homogeneous. Therefore, scientists had to identify a footprint area or “effective upwind source area sensed by the observation” in order to make sense of the measurements. This led to the development of footprint functions weighting the respective contribution of each element of the surface to the measured vertical flux. A promising use of footprint models would be to extend the use of eddy covariance to quantify point source emissions, such as methane emissions from livestock or emissions from vents in geothermal areas. However, most footprint models consider the source at ground level which may not be a valid hypothesis for all point sources as for example livestock. The present work aimed to assess the effect of neglecting the source height on the accuracy of the gas emission prediction. The first step of the work focused on the validation of the footprint model FIDES which take in account the source height. The validation was based on experimental measurements with an artificial source at two heights (0.05 & 1.3m) located at two distances (14 & 24m). For both distances and sampling heights the footprint model provided satisfactory results. Then the second step used FIDES model to perform a sensitivity analysis of the flux prediction error in respect with the source height and the distance from the mast. This analysis showed that the error mainly occurs close to the mast. Indeed, below a critical distance if the source height is not known, assuming it at ground level may induce large error on the flux measurements. The critical distance can be expressed in respect with the mast and the source heights. For example, neglecting the source height for a source lower than 0.15 of the mast height leads to relative error smaller than 10% when the point source was located further than 8 times the mast height. These results can be used to design future experiments in order to minimizing the flux measurements error when the height of the source may not be exactly known by sampling within a defined range from the mast in which the measurement errors remains lo

Cattle methane fluxes measurement over an intensively grazed grassland using eddy covariance

audience: researcherMethane emissions account for 8% of the EU-15 GHG emissions and livestock generates approximately half of these emissions (European Commission, 2009). Recent technological advances in spectroscopy now permit methane flux measurement using eddy covariance. This method has numerous strengths. It can measure fluxes in situ, continuously and across broad areas. This provides information about meadow and cattle emission behaviour throughout the year and across a broad range of climatic conditions. We will present here a one year monitoring of methane exchange between an intensively grazed meadow and the atmosphere obtained using the eddy-covariance method. Methane fluxes exchanged by a grazed meadow were measured continuously since June 2012 at the Dorinne Terrestrial Observatory (50˚ 18’ 44” N; 4˚ 58’ 07” E; 248 m asl.) in Belgium. The site is an intensively pastured meadow of 4.2 ha managed according to the regional common practices where up to 30 Belgian Blue cows are grazing simultaneously. Flux measurements were made with the eddy covariance technique, using a fast CH4 analyzer (Picarro G2311-f) and a sonic anemometer (Campbell Csat3). Carbon dioxide fluxes and various micro-meteorological and soil variables, biomass growth and stocking rate evolution were also measured at the site. Turbulent fluxes were calculated according to standard eddy covariance computation schemes and were filtered for non-stationarity and for low friction velocity (u*) events. During grazing periods, fluxes are dominated by the enteric fermentation source and average 111 nmol m-2 s-1. They are highly variable, probably due to cow movements in and out the measurement footprint and cow digestion rhythm. Despite this spread, a daily emission rhythm is observed with higher emissions during the afternoon. When fluxes are integrated over large periods, methane emissions were found strongly related to cattle stocking rate with a slope of 7.34±0.78 mol CH4 day-1 LSU-1. Further developments are ongoing in order to improve cattle geo-localization through infra-red cameras and individual home-made GPS devices. The two systems will be compared in terms of cost, efficiency and ease of use. During cow-free periods, the methane flux averages 10.5 nmol m-2 s-1 and is highly variable with some production peaks above 100 nmol m-2 s-1. No relation was found between methane fluxes and soil temperature while a weak negative relation was found between methane fluxes and soil humidity. No soil methane absorption has been observed. European Commission. Fifth National Communication from the European Community Under the UN Framework Convention on Climate Change (UNFCCC). Technical Report - 2009 – 038 (2009)

Agriculture et changements climatiques: bilan de carbone d'une prairie pâturée en Région wallonne

Projet D31-1278: Etablissement du bilan de carbone d'une exploitation agricole wallonne pratiquant le système allaitant: effet du climat et de la gestion du pâturag

Quantification of short and long asbestos fibers to assess asbestos exposure: a review of fiber size toxicity.

International audienceThe fibrogenicity and carcinogenicity of asbestos fibers are dependent on several fiber parameters including fiber dimensions. Based on the WHO (World Health Organization) definition, the current regulations focalise on long asbestos fibers (LAF) (Length: L ≥ 5 μm, Diameter: D  3). However air samples contain short asbestos fibers (SAF) (L < 5 μm). In a recent study we found that several air samples collected in buildings with asbestos containing materials (ACM) were composed only of SAF, sometimes in a concentration of ≥10 fibers.L-1. This exhaustive review focuses on available information from peer-review publications on the size-dependent pathogenetic effects of asbestos fibers reported in experimental in vivo and in vitro studies. In the literature, the findings that SAF are less pathogenic than LAF are based on experiments where a cut-off of 5 μm was generally made to differentiate short from long asbestos fibers. Nevertheless, the value of 5 μm as the limit for length is not based on scientific evidence, but is a limit for comparative analyses. From this review, it is clear that the pathogenicity of SAF cannot be completely ruled out, especially in high exposure situations. Therefore, the presence of SAF in air samples appears as an indicator of the degradation of ACM and inclusion of their systematic search should be considered in the regulation. Measurement of these fibers in air samples will then make it possible to identify pollution and anticipate health risk

Electromagnetic simulations of JET ICRF ITER-like antenna with TOPICA and SSWICH asymptotic codes

Multi-megawatt Ion Cyclotron Range of Frequencies (ICRF) heating is routinely used in the JET tokamak. To increase the ICRF heating power available from the A2 antennas, the ICRF ITER-Like Antenna (ILA) was reinstalled for the 2015 JET ITER-like wall experimental campaign. The application of high levels of ICRF power typically results in increased plasma wall interaction which leads to the observation of enhanced influx of metallic impurities in the plasma edge. It is assumed that the impurity production is mainly driven by the parallel component of the Radio-Frequency (RF) antenna electric near-field, E// (parallel to the confinement magnetic field of the tokamak), that is rectified in a thin boundary layer (RF sheath). Torino Polytechnic Ion Cyclotron Antenna (TOPICA) code was used to compute E// field maps in front of the ILA and between its poloidal limiters in the presence of plasma using measured density profiles and various antenna feedings. E// field maps calculated between the poloidal limiters were used to estimate the poloidal distribution of RF-sheath Direct Current (DC) potential in this private region of the ILA and make relative comparison of various antenna electrical settings. For this purpose we used the asymptotic version of the Self-consistent Sheaths and Waves for Ion Cyclotron Heating Slow-Wave (SSWICH-SW) code. These estimations can help to study the formation of RF sheaths around the antenna and even at distant locations (∼3m away)

Agroécologie:utopie ou vision d'avenir?

l’heure où l’agroécologie devient un concept incontournable dans la sphère publique, elle reste encore une notion nébuleuse aux interprétations multiples. Incontour-nable, au point que nombres d’acteurs s’en emparent, empreint d’idéalisme pour certains, d’opportunité politique ou d’avidité mercantile pour d’autres. Nébuleuse, car certains aspects restent encore peu étudiés comme son rôle réel dans l’atténuation du changement climatique, sa contribution, difficile à caractériser, en terme de services à la société, comme les services écosysté-miques, le bien-être et la qualité de vie pour les citoyen·ne·s et les paysan·ne·s en particulier ou enfin son lien intrinsèque avec la lutte pour l’égalité de genre. Ce numéro nous amène ainsi à une compréhension plus profonde et une vision plus systémique de ce que recèle l’agroécologie