Oxaliplatin induces hyperexcitability at motor and autonomic neuromuscular junctions through effects on voltage-gated sodium channels

Oxaliplatin, an effective cytotoxic treatment in combination with 5-fluorouracil for colorectal cancer, is associated with sensory, motor and autonomic neurotoxicity. Motor symptoms include hyperexcitability while autonomic effects include urinary retention, but the cause of these side-effects is unknown. We examined the effects on motor nerve function in the mouse hemidiaphragm and on the autonomic system in the vas deferens. In the mouse diaphragm, oxaliplatin (0.5 mM) induced multiple endplate potentials (EPPs) following a single stimulus, and was associated with an increase in spontaneous miniature EPP frequency. In the vas deferens, spontaneous excitatory junction potential frequency was increased after 30 min exposure to oxaliplatin; no changes in resting Ca(2+) concentration in nerve terminal varicosities were observed, and recovery after stimuli trains was unaffected.In both tissues, an oxaliplatin-induced increase in spontaneous activity was prevented by the voltage-gated Na(+) channel blocker tetrodotoxin (TTX). Carbamazepine (0.3 mM) also prevented multiple EPPs and the increase in spontaneous activity in both tissues. In diaphragm, beta-pompilidotoxin (100 microM), which slows Na(+) channel inactivation, induced multiple EPPs similar to oxaliplatin's effect. By contrast, blockers of K(+) channels (4-aminopyridine and apamin) did not replicate oxaliplatin-induced hyperexcitability in the diaphragm. The prevention of hyperexcitability by TTX blockade implies that oxaliplatin acts on nerve conduction rather than by effecting repolarisation. The similarity between beta-pompilidotoxin and oxaliplatin suggests that alteration of voltage-gated Na(+) channel kinetics is likely to underlie the acute neurotoxic actions of oxaliplatin.

Channelled Waves in Anisotropic Mesh Metamaterials

Channelled waves in 2-D periodic anisotropic L-C mesh metamaterials have been investigated. Circuit simulation and the newly developed analytical model of a unit cell have demonstrated full qualitative agreement for both lossless and lossy cases. Isofrequencies for a lattice unit cell and the circuit simulations of finite meshes have shown that propagating waves are channelled from a point source as pencil beams which can travel only along specific trajectories. The beam direction varies with frequency, and at the resonance frequency, the phase and group velocities of the travelling wave are orthogonal. The effect of losses was explored, and it was shown that losses cause qualitative changes of the channelled wave type. It was proven that the channelled waves do not follow the laws of geometrical optics (Snell's law, specular reflection, etc.) at the interfaces of L-C meshes but are governed by the conditions of phase synchronism and impedance matching. Only in the special case of dual L-C and C-L meshes with the interface parallel to the axis of rectangular grid excited at the resonance frequency (X=1) do the channels follow the trajectories of optical rays. A planar mesh test cell has been designed and used for retrieving the unit cell L-C parameters from the S-parameter measurements.

Analysis and Synthesis of pHEMT Class-E Amplifiers with Shunt Inductor including ON-State Active-Device Resistance Effects

In this theoretical paper, the analysis of the effect that ON-state active-device resistance has on the performance of a Class-E tuned power amplifier using a shunt inductor topology is presented. The work is focused on the relatively unexplored area of design facilitation of Class-E tuned amplifiers where intrinsically low-output-capacitance monolithic microwave integrated circuit switching devices such as pseudomorphic high electron mobility transistors are used. In the paper, the switching voltage and current waveforms in the presence of ON-resistance are analyzed in order to provide insight into circuit properties such as RF output power, drain efficiency, and power-output capability. For a given amplifier specification, a design procedure is illustrated whereby it is possible to compute optimal circuit component values which account for prescribed switch resistance loss. Furthermore, insight into how ON-resistance affects transistor selection in terms of peak switch voltage and current requirements is described. Finally, a design example is given in order to validate the theoretical analysis against numerical simulation.

Spatial Demultiplexing in the sub-millimeter wave band using multlayer free-standing frequency selective surfaces

In this paper, we show that a multilayer freestanding slot array can be designed to give an insertion loss which is significantly lower than the value obtainable from a conventional dielectric backed printed frequency selective surface (FSS). This increase in filter efficiency is highlighted by comparing the performance of two structures designed to provide frequency selective beamsplitting in the quasioptical feed train of a submillimeter wave space borne radiometer. A two layer substrateless FSS providing more than 20 dB of isolation between the bands 316.5â??325.5 GHz and 349.5â??358.5 GHz, gives an insertion loss of 0.6 dB when the filter is orientated at 45 incidence in the TM plane, whereas the loss exhibited by a conventional printed FSS is in excess of 2 dB. A similar frequency response can be obtained in the TE plane, but here a triple screen structure is required and the conductor loss is shown to be comparable to the absorption loss of a dielectric backed FSS. Experimental devices have been fabricated using a precision micromachining technique. Transmission measurements performed in the range 250â??360 GHz are in good agreement with the simulated spectral performance of the individual periodic screens and the two multilayer freestanding FSS structures.

Micromachined 300GHz high Q resonant slot frequency selective surface filter

The design of a low loss quasi-optical beam splitter which is required to provide efficient diplexing of the bands 316.5-325.5 GHz and 349.5-358.5 GHz is presented. To minimise the filter insertion loss, the chosen architecture is a three-layer freestanding array of dipole slot elements. Floquet modal analysis and finite element method computer models are used to establish the geometry of the periodic structure and to predict its spectral response. Two different micromachining approaches have been employed to fabricate close packed arrays of 460 mm long elements in the screens that form the basic building block of the 30mm diameter multilayer frequency selective surface. Comparisons between simulated and measured transmission coefficients for the individual dichroic surfaces are used to determine the accuracy of the computer models and to confirm the suitability of the fabrication methods.

Design optimisation of ring elements for broadband reflectarray antennas

Plane wave scattering from a flat surface consisting of two periodic arrays of ring elements printed on a grounded dielectric sheet is investigated. It is shown that the reflection phase variation as a function of ring diameter is controlled by the difference in the centre resonant frequency of the two arrays. Simulated and measured results at X-band demonstrate that this parameter can be used to reduce the gradient and improve the linearity of the reflection phase versus ring size slope. These are necessary conditions for the re-radiating elements to maximise the bandwidth of a microstrip reflectarray antenna. The scattering properties of a conventional dual resonant multilayer structure and an array of concentric rings printed on a metal backed dielectric substrate are compared and the trade-off in performance is discussed.