Farnesoid X receptor and liver X receptor ligands initiate formation of coated platelets

The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity. We, therefore, investigated whether ligands for the LXR and FXR receptors were capable of priming platelets to the activated state without stimulation by platelet agonists. Treatment of platelets with ligands for LXR and FXR converted platelets to the procoagulant state, with increases in phosphatidylserine exposure, platelet swelling, reduced membrane integrity, depolarization of the mitochondrial membrane, and microparticle release observed. Additionally, platelets also displayed features associated with coated platelets such as P-selectin exposure, fibrinogen binding, fibrin generation that is supported by increased serine protease activity, and inhibition of integrin αIIbβ3. LXR and FXR ligand-induced formation of coated platelets was found to be dependent on both reactive oxygen species and intracellular calcium mobilization, and for FXR ligands, this process was found to be dependent on cyclophilin D. We conclude that treatment with LXR and FXR ligands initiates coated platelet formation, which is thought to support coagulation but results in desensitization to platelet stimuli through inhibition of αIIbβ3 consistent with their ability to inhibit platelet function and stable thrombus formation in vivo

Radio detection of cosmic ray air showers with LOPES

In the last few years, radio detection of cosmic ray air showers has experienced a true renaissance, becoming manifest in a number of new experiments and simulation efforts. In particular, the LOPES project has successfully implemented modern interferometric methods to measure the radio emission from extensive air showers. LOPES has confirmed that the emission is coherent and of geomagnetic origin, as expected by the geosynchrotron mechanism, and has demonstrated that a large scale application of the radio technique has great potential to complement current measurements of ultra-high energy cosmic rays. We describe the current status, most recent results and open questions regarding radio detection of cosmic rays and give an overview of ongoing research and development for an application of the radio technique in the framework of the Pierre Auger Observatory.Comment: 8 pages; Proceedings of the CRIS2006 conference, Catania, Italy; to be published in Nuclear Physics B, Proceedings Supplement

Air Shower Measurements with the LOPES Radio Antenna Array

LOPES is set up at the location of the KASCADE-Grande extensive air shower experiment in Karlsruhe, Germany and aims to measure and investigate radio pulses from Extensive Air Showers. Since radio waves suffer very little attenuation, radio measurements allow the detection of very distant or highly inclined showers. These waves can be recorded day and night, and provide a bolometric measure of the leptonic shower component. LOPES is designed as a digital radio interferometer using high bandwidths and fast data processing and profits from the reconstructed air shower observables of KASCADE-Grande. The LOPES antennas are absolutely amplitude calibrated allowing to reconstruct the electric field strength which can be compared with predictions from detailed Monte Carlo simulations. We report about the analysis of correlations present in the radio signals measured by the LOPES 30 antenna array. Additionally, LOPES operates antennas of a different type (LOPES-STAR) which are optimized for an application at the Pierre Auger Observatory. Status, recent results of the data analysis and further perspectives of LOPES and the possible large scale application of this new detection technique are discussed.Comment: 8 pages, 10 figures, Contribution to the Arena 2008 conference, Rome, June 200