The Ca(v)2.3 calcium channel antagonist SNX-482 reduces dorsal horn neuronal responses in a rat model of chronic neuropathic pain

Neuropathic pain is a difficult state to treat, characterized by alterations in sensory processing that can include allodynia (touch-evoked pain). Evidence exists for nerve damage-induced plasticity in both transmission and modulatory systems, including changes in voltage-dependent calcium channel (VDCC) expression and function; however, the role of Ca(v)2.3 calcium channels has not clearly been defined. Here, the effects of SNX-482, a selective Ca(v)2.3 antagonist, on sensory transmission at the spinal cord level have been investigated in the rat. The spinal nerve ligation (SNL) model of chronic neuropathic pain [Kim & Chung, (1992) Pain, 50, 355-363] was used to induce mechanical allodynia, as tested on the ipsilateral hindpaw. In vivo electrophysiological measurements of dorsal horn neuronal responses to innocuous and noxious electrical and natural stimuli were made after SNL and compared to sham-operated animals. Spinal SNX-482 (0.5-4 mu g/50 mu L) exerted dose-related inhibitions of noxious C-fibre- and A delta-fibre-mediated neuronal responses in conditions of neuropathy, but not in sham-operated animals. Measures of spinal cord hyperexcitability and nociception were most susceptible to SNX-482. In contrast, non-noxious A beta-mediated responses were not affected by SNX-482. Moreover, responses to innocuous mechanical and also thermal stimuli were more sensitive to SNX-482 in SNL than control animals. This study is the first to demonstrate an antinociceptive role for SNX-482-sensitive channels in dorsal horn neurons during neuropathy. These data are consistent with plasticity in Ca(V)2.3 calcium channel expression and suggest a potential selective target to reduce nociceptive transmission during conditions of nerve damage.

Disparity with respect to a local reference plane as a dominant cue for stereoscopic depth relief

Earlier studies showed that the disparity with respect to other visible points could not explain stereoacuity performance, nor could various spatial derivatives of disparity [Glennerster, A., McKee, S. P., & Birch, M. D. (2002). Evidence of surface-based processing of binocular disparity. Current Biology, 12:825-828; Petrov, Y., & Glennerster, A. (2004). The role of the local reference in stereoscopic detection of depth relief. Vision Research, 44:367-376.] Two possible cues remain: (i) local changes in disparity gradient or (ii) disparity with respect to an interpolated line drawn through the reference points. Here, we aimed to distinguish between these two cues. Subjects judged.. in a two AFC paradigm, whether a target dot was in front of a plane defined by three reference dots or, in other experiments, in front of a line defined by two reference dots. We tested different slants of the reference line or plane and different locations of the target relative to the reference points. For slanted reference lines or plane, stereoacuity changed little as the target position was varied. For judgments relative to a frontoparallel reference line, stereoacuity did vary with target position, but less than would be predicted by disparity gradient change. This provides evidence that disparity with respect to the reference plane is an important cue. We discuss the potential advantages of this measure in generating a representation of surface relief that is invariant to viewpoint transformations. (c) 2006 Elsevier Ltd. All rights reserved.

Micromachined waveguide antennas for 1.6 THz

A new type of horn antenna for operation at 1.6 THz, that can be fabricated monolithically with 1/4-height micromachined waveguide, is described. Height, limitations imposed by the micromachining process are overcome by removing a tapered slot in the upper surface of a scalar horn, allowing the E-plane fields to extend outside the confines of the metallic structure before radiation, with a consequent reduction in E-plane beamwidth. 1.6 THz radiation pattern measurements for different designs show that, while there is scope for further optimisation, 3 dB beamwidths of 24 degrees and 17.5 degrees in the E- and H-planes, respectively, can be achieved.

Infrared filters for space-flight focal plane array applications

Infrared filters and coatings have been employed on many sensing radiometer instruments to measure the thermal emission profiles and concentrations of certian chemical constituents found in planetary atmospheres. The High Resolution Dynamics Limb Sounder ( HIRDLS) is an example of the most recent developments in limb-viewing radiometry by employing a cooled focal plane detector array to provide simultaneous multi-channel monitoring of emission from gas and aerosols over an altitude range between 8 - 70 km. The use of spectrally selective cooled detectors in focal plane arrays has simplified the optical layout of radiometers, greatly reducing the number of components in the optical train. this has inevitably led to increased demands for the enviromnetal durability of the focal plane filters because of the need to cut sub-millimeter sizes, whilst maintaining an optimal spectral performance. Additionally the remaining refractive optical elements require antireflection coatings which must cover the entire spectral range of the focal plane array channels, in this case 6 to 18µm, with a minimum of reflection and absorption. This paper describes the optical layout and spectral design requirements for filteriong in the HIRDLS instrument, and reports progress on the manufacturing and testing of the sub-millimetre sized cooled filters. We also report on the spectral and environmental performance of prototype wideband antireflection coatings which satisfy the requirements above.

High-performance infrared filters for the HIRDLS 21-channel focal plane detector array

The High Resolution Dynamics Limb Sounder is described, with particular reference to the atmospheric measurements to be made and the rationale behind the measurement strategy. The demands this strategy places on the filters to be used in the instrument and the designs to which this leads to are described. A second set of filters at an intermediate image plane to reduce "Ghost Imaging" is discussed together with their required spectral properties. A method of combining the spectral characteristics of the primary and secondary filters in each channel are combined together with the spectral response of the detectors and other optical elements to obtain the system spectral response weighted appropriately for the Planck function and atmospheric limb absorption. This method is used to demonstrate whether the out-of-band spectral blocking requirement for a channel is being met and an example calculation is demonstrated showing how the blocking is built up for a representative channel. Finally, the techniques used to produce filters of the necessary sub-millimetre sizes together with the testing methods and procedures used to assess the environmental durability and establish space flight quality are discussed.

Use of Megasphaera elsdenii NCIMB41125 as a probiotic for early-lactation dairy cows: effects on rumen pH and fermentation patterns

Multiparous rumen-fistulated Holstein cows were fed, from d 1 to 28 post-calving, an ad libitum TMR containing (g/kg DM) grass silage (196), corn silage (196), wheat (277), soybean meal (100), and other feeds (231) with CP, NDF, starch and water soluble carbohydrate concentrations of 176, 260, 299 and 39 g/kg DM respectively and ME of 12.2 MJ/kg DM. Treatments consisting of a minimum of 1010 cfu Megasphaera elsdenii NCIMB 41125 in 250 ml solution (MEGA) or 250 ml of autoclaved M. elsdenii (CONT) were administered via the rumen cannula on d 3 and 12 of lactation (n=7 per treatment). Mid-rumen pH was measured every 15 minutes and eating and ruminating behavior was recorded for 24 h on d 2, 4, 6, 8, 11, 13, 15, 17, 22 and 28. Rumen fluid for VFA and lactic acid (LA) analysis was collected at 11 timepoints on each of d 2, 4, 6, 13 and 15. Data were analysed as repeated measures using the Glimmix (LA data) or Mixed (all other data) procedures of SAS with previous 305 d milk yield and d 2 measurements as covariates where appropriate. Milk yield was higher (CONT 43.0 vs MEGA 45.4 ±0.75 kg/d, P=0.051) and fat concentration was lower (CONT 45.6 vs MEGA 40.4 ±1.05 g/kg, P=0.005) in cows that received MEGA. Time spent eating (263 ±15 min/d) and ruminating (571 ±13 min/d), DM intake (18.4 ±0.74 kg/d), proportion of each 24 h period with rumen pH below 5.6 (3.69 ±0.94 h) and LA concentrations (2.00 mM) were similar (P>0.327) across treatments. Ruminal total VFA concentration (104 ±3 mM) was similar (P=0.404) across treatments, but a shift from acetate (CONT 551 vs MEGA 524 ±14 mmol/mol VFA, P=0.161) to propionate production (CONT 249 vs MEGA 275 ±11 mmol/mol VFA, P=0.099) meant that the acetate:propionate ratio (CONT 2.33 vs MEGA 1.94 ±0.15) was reduced (P=0.072) in cows that received MEGA. This study provides evidence that supplementation of early lactation dairy cows with MEGA alters rumen fermentation patterns in favour of propionate, with potential benefits for animal health and productivity.

Fabrication and characterization of micromachined rectangular waveguide components for use at millimeter-wave and terahertz frequencies

The fabrication and characterization of micromachined reduced-height air-filled rectangular waveguide components suitable for integration is reported in this paper. The lithographic technique used permits structures with heights of up to 100 μm to be successfully constructed in a repeatable manner. Waveguide S-parameter measurements at frequencies between 75-110 GHz using a vector network analyzer demonstrate low loss propagation in the TE10 mode reaching 0.2 dB per wavelength. Scanning electron microscope photographs of conventional and micromachined waveguides show that the fabrication technique can provide a superior surface finish than possible with commercially available components. In order to circumvent problems in efficiently coupling free-space propagating beams to the reduced-height G-band waveguides, as well as to characterize them using quasi-optical techniques, a novel integrated micromachined slotted horn antenna has been designed and fabricated, E-, H-, and D-plane far-field antenna pattern measurements at different frequencies using a quasi-optical setup show that the fabricated structures are optimized for 180-GHz operation with an E-plane half-power beamwidth of 32° elevated 35° above the substrate, a symmetrical H-plane pattern with a half-power beamwidth of 23° and a maximum D-plane cross-polar level of -33 dB. Far-field pattern simulations using HFSS show good agreement with experimental results.

Regional implications of macro-economic, sectoral and company changes in the development of technopoles in Britain and France

This paper reports the proceedings of a conference held at Reading University in 1993 which addressed the issues of new technological developments at the regional and sub-regional levels in Britain and France. These new technological clusters - the `Technopoles' - are investigated in a series of papers in both English and French which examines their spatial, sectoral and economic aspects to determine what lessons can be learned from their development and what their future economic significance is likely to be. Two recurring themes are of particular significance in the papers - the link between R& D and regional development, and the different forms which innovation assumes within the various technopoles under scrutiny.

Plane wave discontinuous Galerkin methods for the 2D Helmholtz equation: analysis of the $p$-version

Plane wave discontinuous Galerkin (PWDG) methods are a class of Trefftz-type methods for the spatial discretization of boundary value problems for the Helmholtz operator $-\Delta-\omega^2$, $\omega>0$. They include the so-called ultra weak variational formulation from [O. Cessenat and B. Després, SIAM J. Numer. Anal., 35 (1998), pp. 255–299]. This paper is concerned with the a priori convergence analysis of PWDG in the case of $p$-refinement, that is, the study of the asymptotic behavior of relevant error norms as the number of plane wave directions in the local trial spaces is increased. For convex domains in two space dimensions, we derive convergence rates, employing mesh skeleton-based norms, duality techniques from [P. Monk and D. Wang, Comput. Methods Appl. Mech. Engrg., 175 (1999), pp. 121–136], and plane wave approximation theory.

Plane wave approximation of homogeneous Helmholtz solutions

In this paper, we study the approximation of solutions of the homogeneous Helmholtz equation Δu + ω 2 u = 0 by linear combinations of plane waves with different directions. We combine approximation estimates for homogeneous Helmholtz solutions by generalized harmonic polynomials, obtained from Vekua’s theory, with estimates for the approximation of generalized harmonic polynomials by plane waves. The latter is the focus of this paper. We establish best approximation error estimates in Sobolev norms, which are explicit in terms of the degree of the generalized polynomial to be approximated, the domain size, and the number of plane waves used in the approximations.

Plane wave approximation in linear elasticity

We consider the approximation of solutions of the time-harmonic linear elastic wave equation by linear combinations of plane waves. We prove algebraic orders of convergence both with respect to the dimension of the approximating space and to the diameter of the domain. The error is measured in Sobolev norms and the constants in the estimates explicitly depend on the problem wavenumber. The obtained estimates can be used in the h- and p-convergence analysis of wave-based finite element schemes.

2D hexagonal mesoporous platinum films exhibiting biaxial, in-plane pore alignment

The synthesis of 2D hexagonal mesoporous platinum films with biaxial, in-plane pore alignment is demonstrated by electrodeposition through an aligned lyotropic liquid crystal templating phase. Shear force is used to align a hexagonal lyotropic liquid crystalline templating phase of an inexpensive and a commercially available surfactant, C16EO10, at the surface of an electrode. Electrodeposition and subsequent characterisation of the films produced shows that the orientation and alignment of the phase is transferred to the deposited material. Transmission electron microscopy confirms the expected nanostructure of the films, whilst transmission and grazing incidence small angle X-ray scattering analysis confirms biaxial, in plane alignment of the pore structure. In addition further electrochemical studies in dilute sulfuric acid and methanol show that the pores are accessible to electrolyte solution as indicated by a large current flow; the modified electrode therefore has a high surface area, that catalyses methanol oxidation, and the pores have a very large aspect ratio (of theoretical maximum 2 × 105). Films with such aligned mesoporosity will advance the field of nanotechnology where the control of pore structure is paramount. The method reported is sufficiently generic to be used to control the structure and order of many materials, thus increasing the potential for the development of a wide range of novel electronic and optical devices.

Internal wave drag in stratified flow over mountains on a beta plane

The impact of the variation of the Coriolis parameter f on the drag exerted by internal Rossby-gravity waves on elliptical mountains is evaluated using linear theory, assuming constant wind and static stability and a beta-plane approximation. Previous calculations of inertia-gravity wave drag are thus extended in an attempt to establish a connection with existing studies on planetary wave drag, developed primarily for fluids topped by a rigid lid. It is found that the internal wave drag for zonal westerly flow strongly increases relative to that given by the calculation where f is assumed to be a constant, particularly at high latitudes and for mountains aligned meridionally. Drag increases with mountain width for sufficiently wide mountains, reaching values much larger than those valid in the non-rotating limit. This occurs because the drag receives contributions from a low wavenumber range, controlled by the beta effect, which accounts for the drag amplification found here. This drag amplification is shown to be considerable for idealized analogues of real mountain ranges, such as the Himalayas and the Rocky mountains, and comparable to the barotropic Rossby wave drag addressed in previous studies.