Antihypertensive Drug Guanabenz Is Active In Vivo against both Yeast and Mammalian Prions

Background: Prion-based diseases are incurable transmissible neurodegenerative disorders affecting animals and humans. [br/] Methodology/Principal Findings: Here we report the discovery of the in vivo antiprion activity of Guanabenz (GA), an agonist of a2-adrenergic receptors routinely used in human medicine as an antihypertensive drug. We isolated GA in a screen for drugs active in vivo against two different yeast prions using a previously described yeast-based two steps assay. GA was then shown to promote ovine PrPSc clearance in a cell-based assay. These effects are very specific as evidenced by the lack of activity of some GA analogues that we generated. GA antiprion activity does not involve its agonist activity on a2-adrenergic receptors as other chemically close anti-hypertensive agents possessing related mechanism of action were found inactive against prions. Finally, GA showed activity in a transgenic mouse-based in vivo assay for ovine prion propagation, prolonging slightly but significantly the survival of treated animals. [br/] Conclusion/Significance: GA thus adds to the short list of compounds active in vivo in animal models for the treatment of prion-based diseases. Because it has been administrated for many years to treat hypertension on a daily basis, without major side-effects, our results suggest that it could be evaluated in human as a potential treatment for prion-based diseases

Macro-Clusters, a Way to Adapt New Technologies in Existing Large Computing Clusters

A series of new interconnect technologies are emerging on the market, HyperTransport PCI-Express, Infiniband and 10 Gigabit Ethernet. Some are very interesting as cluster interconnects and others not at all. A description is made of methods to use this cluster oriented interconnects in different ways. In order to adapt easily to existing clusters the term of Macro-Clusters is introduced to define small sub-clusters with a defined function that can be used independently or coupled to large cluster networks. Some notice is given on how to interconnect hardware and software of the different technologies and some remarks about cost performance relations are included. In the Appendix test results are mentioned for bandwidth and connections to the CERN storage system

Two-photon excitation in the life sciences: From observation to action

International audienceTwo-photon (TP) excitation of organic chromophores is of great interest for decades, as applications of such phenomena from 3-dimentional (3D) microfabrication to optical limiting and optical data storage, are of increasing importance. More recently, two-photon excitation found important applications in biology, notably in two-photon excited microscopy (TPEM) or two-photon photodynamic therapy (2P-PDT). Nevertheless, these techniques were using dyes or sensitizers designed for one-photon processes with low two-photon response. The lack of efficient molecules specifically designed for two-photon applications has led us to design new chromophores for biological applications with increased sensitivity to two-photon excitation and specifically added properties useful in biological media, such as water solubility. Here we describe the molecular engineering of such dyes mainly for cell and small animal observation by TPEM and their conjugation to magnetic nanoparticles and bio-nanoparticles such as viruses.We will then focus on the possibility to use photochemical reaction for cell triggering by two-photon photorelease of biologically active substances the so-called two-photon uncaging

System Development and Performance Testing of a W-Band Gyrotron

A high-power W-band gyrotron has been designed and performance tested in Korea, with an output power in the range of tens of kilowatts. The gyrotron consists of a diode-type electron gun operating at 40 kV, a TE6,2 mode interaction cavity, and a mode converter for producing a highly Gaussian output mode beam. Presented here are the detailed component design procedure and the experimental results of the gyrotron's performance evaluation. A maximum power of 62 kW was achieved with an efficiency of 22 %, and a highly Gaussian output beam was observed. The gyrotron's output beam is analyzed, and its transmission through an oversized waveguide is discussed. This gyrotron is the first gyrotron developed in Korea with high power greater than 10 kW and high frequency greater than 90 GHz.close