The structure of the agrochemical fungicidal 4-Chloro-3-(3,5-dichloropheny)-1H-pyrazole, RPA 406194 and related compounds

The difficulties to obtain convenient monocrystals of the important fungicide RPA 406194 have been overcome by a combination of solid state 13C NMR, X-ray powder diffraction and molecular modeling. The compound, a 3-aryl tautomer, crystallizes forming infinite chains of molecules bonded by N–H· · ·N hydrogen bonds, leading to needle-shaped crystals. The tautomerism (equilibrium constant and energy barrier) of this compound in solution has been studied

Fast Timing Analysis of Cygnus X-1 using SPI on board INTEGRAL

For the very first time, we report the high frequency analysis of Cyg X-1 up to hard X-ray using SPI on-board INTEGRAL. After analyzing the possible contribution fromthe background, and using INTEGRAL archive from March 2005 to May 2008, Power Density Spectra (PDS) were obtained until 130 keV. First, we show that their overall shape is very similar to that observed at lower energies, as they are well described by sets of Lorentzians. The strength of this fast variability (up to 40 Hz) does not drop at high energy since we show that it remains at ~25% rms, even in the highest energy bands. Second, the hard X-ray variability patterns of Cyg X-1 are state dependent: the softer the spectrum (or the lower the hardness ratio), the lower the total fractional variability and the higher the typical frequencies observed. The strength of total variability as a function of energy and state is then investigated. By comparison with simultaneous and published RXTE/PCA data, we showed that in the hard state, it remains quite constant in the 2-130 keV energy range. In our softer state, it is also flat until 50 keV and may increase at higher energy. The implications of this behavior on the models are then discussed.Comment: 12 pages, 10 figures, accepted for publication in Ap

NMR Time Reversal Experiments in Highly Polarised Liquid 3He-4He Mixtures

Long-range magnetic interactions in highly magnetised liquids (laser-polarised 3He-4He dilute mixtures at 1 K in our experiment) introduce a significant non-linear and non-local contribution to the evolution of nuclear magnetisation that leads to instabilities during free precession. We recently demonstrated that a multi-echo NMR sequence, based on the magic sandwich pulse scheme developed for solid-state NMR, can be used to stabilise the magnetisation against the effect of distant dipolar fields. Here, we report investigations of echo attenuation in an applied field gradient that show the potential of this NMR sequence for spin diffusion measurements at high magnetisation densities.Comment: Accepted for publication in the Journal of Low Temperature Physic

A novel inhibitor of p75-neurotrophin receptor improves functional outcomes in two models of traumatic brain injury.

The p75 neurotrophin receptor is important in multiple physiological actions including neuronal survival and neurite outgrowth during development, and after central nervous system injury. We have discovered a novel piperazine-derived compound, EVT901, which interferes with p75 neurotrophin receptor oligomerization through direct interaction with the first cysteine-rich domain of the extracellular region. Using ligand binding assays with cysteine-rich domains-fused p75 neurotrophin receptor, we confirmed that EVT901 interferes with oligomerization of full-length p75 neurotrophin receptor in a dose-dependent manner. Here we report that EVT901 reduces binding of pro-nerve growth factor to p75 neurotrophin receptor, blocks pro-nerve growth factor induced apoptosis in cells expressing p75 neurotrophin receptor, and enhances neurite outgrowth in vitro Furthermore, we demonstrate that EVT901 abrogates p75 neurotrophin receptor signalling by other ligands, such as prion peptide and amyloid-β. To test the efficacy of EVT901 in vivo, we evaluated the outcome in two models of traumatic brain injury. We generated controlled cortical impacts in adult rats. Using unbiased stereological analysis, we found that EVT901 delivered intravenously daily for 1 week after injury, reduced lesion size, protected cortical neurons and oligodendrocytes, and had a positive effect on neurological function. After lateral fluid percussion injury in adult rats, oral treatment with EVT901 reduced neuronal death in the hippocampus and thalamus, reduced long-term cognitive deficits, and reduced the occurrence of post-traumatic seizure activity. Together, these studies provide a new reagent for altering p75 neurotrophin receptor actions after injury and suggest that EVT901 may be useful in treatment of central nervous system trauma and other neurological disorders where p75 neurotrophin receptor signalling is affected