Administration of DNA Plasmid Coding Protein Aggregating Domain Induces Inflammatory Bone Loss.

Background: Plasmids coding protein aggregation polypeptides from different sources have beenproposed as genetic adjuvants for DNA vaccines. We reported that a plasmid (pATRex), encompassing the DNA sequence for the von Willebrand A (vWA/A) domain of the Anthrax Toxin Receptor-1 (ANTXR-1, alias TEM8, Tumor Endothelial Marker 8), acts as strong immune adjuvant by inducing formation of insoluble intracellular aggregates and subsequent cell death. Aims: In the present study we addressed the question of whether there is any substantial immunotoxicity associated with the use of self-aggregating proteins as genetic adjuvants. Results: Here we report, by mean of histology, X-ray and molecular examinations of bone specimens, the unexpected finding that intramuscular injection of pATRex in mice triggers, per se, severe bone loss (osteoporosis) independently from the sex and genotype of the treated animals. Conclusion: Even though the study suggests that proteinaceous “sticky “ adjuvants are unlikely to find their way into practical vaccination, the information gained is of value as ATRex injections could provide an additional, simplified, mouse model of osteoporosis. Moreover, our results provide an experimental support to the hypothesis that proteotoxic aggregates chronically activate the innate immune system in amyloid and aggregosome disorders

Approximation of Fourier Integral Operators by Gabor multipliers

A general principle says that the matrix of a Fourier integral operator with respect to wave packets is concentrated near the curve of propagation. We prove a precise version of this principle for Fourier integral operators with a smooth phase and a symbol in the Sjoestrand class and use Gabor frames as wave packets. The almost diagonalization of such Fourier integral operators suggests a specific approximation by (a sum of) elementary operators, namely modified Gabor multipliers. We derive error estimates for such approximations. The methods are taken from time-frequency analysis.Comment: 22. page

3D static and time-dependent modelling of a dc transferred arc twin torch system

International audienceThe transferred arc plasma torch device consists of two electrodes generating a plasma arc sustained by means of an electric current flowing through the body of the discharge. Modeling works investigating of transferred electric arc discharges generated between two suspended metallic electrodes, in the so called twin torch configuration, are scarce. The discharge generated by this particular plasma source configuration is characterized by a complex shape and fluid dynamics and needs a 3D description in order to be realistically predicted. The extended discharge length that goes from the tungsten pencil cathode to the flat copper anode without any particular confinement wall and the fluid dynamics and magnetic forces acting on the arc may induce an unsteady behavior. In order to capture the dynamic behavior of a twin torch discharge, a 3D time dependent plasma arc model has been developed using a customized commercial code FLUENT form in both Local Thermodynamic Equilibrium (LTE) and non-LTE. A two temperature (2T) model has been developed taking into account only the thermal non-equilibrium effects in argon plasma. The main differences between LTE and 2T models results concern the increased extension of the horizontal section of the discharge and the predicted reduced (of about 60-80V) voltage drop between the electrodes when using a 2T model