High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain

Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 µM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherin-positive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain

Phonon-induced quadrupolar ordering of the magnetic superconductor TmNi2_2B2_2C

We present synchrotron x-ray diffraction studies revealing that the lattice of thulium borocarbide is distorted below T_Q = 13.5 K at zero field. T_Q increases and the amplitude of the displacements is drastically enhanced, by a factor of 10 at 60 kOe, when a magnetic field is applied along [100]. The distortion occurs at the same wave vector as the antiferromagnetic ordering induced by the a-axis field. A model is presented that accounts for the properties of the quadrupolar phase and explains the peculiar behavior of the antiferromagnetic ordering previously observed in this compound.Comment: submitted to PR

Pauli Paramagnetic Effects on Vortices in Superconducting TmNi2B2C

The magnetic field distribution around the vortices in TmNi2B2C in the paramagnetic phase was studied experimentally as well as theoretically. The vortex form factor, measured by small-angle neutron scattering, is found to be field independent up to 0.6 Hc2 followed by a sharp decrease at higher fields. The data are fitted well by solutions to the Eilenberger equations when paramagnetic effects due to the exchange interaction with the localized 4f Tm moments are included. The induced paramagnetic moments around the vortex cores act to maintain the field contrast probed by the form factor.Comment: 4 pages, 4 figure

Fermi surface and order parameter driven vortex lattice structure transitions in twin-free YBa2Cu3O7

We report on small-angle neutron scattering studies of the intrinsic vortex lattice (VL) structure in detwinned YBa2Cu3O7 at 2 K, and in fields up to 10.8 T. Because of the suppressed pinning to twin-domain boundaries, a new distorted hexagonal VL structure phase is stabilized at intermediate fields. It is separated from a low-field hexagonal phase of different orientation and distortion by a first-order transition at 2.0(2) T that is probably driven by Fermi surface effects. We argue that another first-order transition at 6.7(2) T, into a rhombic structure with a distortion of opposite sign, marks a crossover from a regime where Fermi surface anisotropy is dominant, to one where the VL structure and distortion is controlled by the order-parameter anisotropy.Comment: 4 pages, 3 figures (2 color), minor change

Temperature Dependence of the Flux Line Lattice Transition into Square Symmetry in Superconducting LuNi2_2B2_2C

We have investigated the temperature dependence of the H || c flux line lattice structural phase transition from square to hexagonal symmetry, in the tetragonal superconductor LuNi_2B_2C (T_c = 16.6 K). At temperatures below 10 K the transition onset field, H_2(T), is only weakly temperature dependent. Above 10 K, H_2(T) rises sharply, bending away from the upper critical field. This contradicts theoretical predictions of H_2(T) merging with the upper critical field, and suggests that just below the H_c2(T)-curve the flux line lattice might be hexagonal.Comment: 4 pages, 3 figure

Patient level pooled analysis of 68,500 patients from seven major vitamin D fracture trials in the US and Europe

Objectives To identify participants’ characteristics that influence the anti-fracture efficacy of vitamin D or vitamin D plus calcium with respect to any fracture, hip fracture, and clinical vertebral fracture and to assess the influence of dosing regimens and co-administration of calcium. Design Individual patient data analysis using pooled data from randomised trials. Data sources Seven major randomised trials of vitamin D with calcium or vitamin D alone, yielding a total of 68 517 participants (mean age 69.9 years, range 47-107 years, 14.7% men). Study selection Studies included were randomised studies with at least one intervention arm in which vitamin D was given, fracture as an outcome, and at least 1000 participants. Data synthesis Logistic regression analysis was used to identify significant interaction terms, followed by Cox’s proportional hazards models incorporating age, sex, fracture history, and hormone therapy and bisphosphonate use. Results Trials using vitamin D with calcium showed a reduced overall risk of fracture (hazard ratio 0.92, 95% confidence interval 0.86 to 0.99, P=0.025) and hip fracture (all studies: 0.84, 0.70 to 1.01, P=0.07; studies using 10 μg of vitamin D given with calcium: 0.74, 0.60 to 0.91, P=0.005). For vitamin D alone in daily doses of 10 μg or 20 μg, no significant effects were found. No interaction was found between fracture history and treatment response, nor any interaction with age, sex, or hormone replacement therapy. Conclusion This individual patient data analysis indicates that vitamin D given alone in doses of 10-20 μg is not effective in preventing fractures. By contrast, calcium and vitamin D given together reduce hip fractures and total fractures, and probably vertebral fractures, irrespective of age, sex, or previous fractures.The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221. AA acknowledges personal funding from the UK Medical Research Council and Chief Scientist Office of the Scottish Government Health Directorates

Conceptual design and thermal analysis of a modular cryostat for one single coil of a 10 MW offshore superconducting wind turbine

Superconducting generators show the potential to reduce the head mass of large offshore wind turbines. A 10 MW offshore superconducting wind turbine has been investigated in the SUPRAPOWER project. The superconducting coils based on MgB2 tapes are supposed to work at cryogenic temperature of 20 K. In this paper, a novel modular rotating cryostat was presented for one single coil of the superconducting wind turbine. The modular concept and cryogen-free cooling method were proposed to fulfil the requirements of handling, maintenance, reliability of long term and offshore operations. Two stage Gifford-McMahon cryocoolers were used to provide cooling source. Supporting rods made of titanium alloy were selected as support structures of the cryostat in aim of reducing the heat load. The thermal performance in the modular cryostat was carefully investigated. The heat load applied to the cryocooler second stage was 2.17 W@20 K per coil. The corresponding temperature difference along the superconducting coil was only around 1 K.European Commision's FP