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.

Excited ions in intense femtosecond laser pulses: Laser-induced recombination

Electron-ion recombination in a laser-induced electron recollision is of fundamental importance as the underlying mechanism responsible for the generation of high harmonic radiation, and hence for the production of attosecond pulse trains in the extreme ultraviolet and soft X-ray spectral regions. By using an ion beam target, remotely prepared to be partially in long-lived excited states, the recombination process has for the first time been directly observed and studied.

Local Conentration of Waves due to Abrupt Alongshore Variation of Nearshore Bathymetry

Small-scale physical and numerical experiments were conducted to investigate the local concentration of waves (monochromatic and group) due to abrupt change of nearshore bathymetry in alongshore direction. Wave run-up motions along the shoreline were measured using an image analysis technique to compare localized concentration of wave energy, when waves propagate a over bathymetry composing rhythmic patterns of mild/steep slope bottom configurations. Measured alongshore variation of maximum wave run-up heights showed significant peak near the boundary, which has sudden alongshore change of depth, both under monochromatic and group wave trains. This phenomenon is found to be due to interaction of waves with neashore currents, which is further enhanced by excitation of long wave components by breaking of group waves. Furthermore, this paper discusses results of preliminary experiments carried out to test the effectiveness of several shore protection structure layouts in mitigating such wave concentrations. Numerical simulations were performed by using a model developed based on Nwogu (1993) Boussinesq-type equations; coupled with a transport equation to model energy dissipation due to wave breaking.

Comparison of parallel and perpendicular polarized counterpropagating light for suppressing high harmonic generation

The use of counterpropagating laser pulses to suppress high harmonic generation (HHG) is investigated experimentally for pulses polarized parallel or perpendicular to the driving laser pulse. It is shown for the first time that perpendicularly polarized pulses can suppress HHG. The intensity of the counterpropagating pulse required for harmonic suppression is found to be much larger for perpendicular polarization than for parallel polarization, in good agreement with simple models of the harmonic suppression. These results have applications to quasi-phase-matching of HHG with trains of counterpropagating pulses. (C) 2007 Optical Society of America.

The Source of 3 Minute Magnetoacoustic Oscillations in Coronal Fans

We use images of high spatial, spectral, and temporal resolution, obtained using both ground- and space-based instrumentation, to investigate the coupling between wave phenomena observed at numerous heights in the solar atmosphere. Analysis of 4170 Å continuum images reveals small-scale umbral intensity enhancements, with diameters ~0."6, lasting in excess of 30 minutes. Intensity oscillations of ˜3 minutes are observed to encompass these photospheric structures, with power at least three orders of magnitude higher than the surrounding umbra. Simultaneous chromospheric velocity and intensity time series reveal an 87?±8? out-of-phase behavior, implying the presence of standing modes created as a result of partial wave re?ection at the transition region boundary. We ?nd a maximum waveguide inclination angle of˜40? between photospheric and chromospheric heights, combined with a radial expansion factor of <76%. An average blueshifted Doppler velocity of ˜1.5 km s-1, in addition to a time lag between photospheric and chromospheric oscillatory phenomena, con?rms the presence of upwardly propagating slow-mode waves in the lower solar atmosphere. Propagating oscillations in EUV intensity are detected in simultaneous coronal fan structures, with a periodicity of 172±17 s and a propagation velocity of 45±7 km s-1. Numerical simulations reveal that the damping of the magnetoacoustic wave trains is dominated by thermal conduction. The coronal fans are seen to anchor into the photosphere in locations where large-amplitude umbral dot (UD) oscillations manifest. Derived kinetic temperature and emission measure time series display prominent outof-phase characteristics, and when combined with the previously established sub-sonic wave speeds, we conclude that the observed EUV waves are the coronal counterparts of the upwardly propagating magnetoacoustic slow modes detected in the lower solar atmosphere. Thus, for the ?rst time, we reveal how the propagation of 3 minute magnetoacoustic waves in solar coronal structures is a direct result of amplitude enhancements occurring in photospheric UDs.photospheric UDs.

Evidence reasoning for event inference in smart transport video surveillance

In this paper we present a new event recognition framework, based on the Dempster-Shafer theory of evidence, which combines the evidence from multiple atomic events detected by low-level computer vision analytics. The proposed framework employs evidential network modelling of composite events. This approach can effectively handle the uncertainty of the detected events, whilst inferring high-level events that have semantic meaning with high degrees of belief. Our scheme has been comprehensively evaluated against various scenarios that simulate passenger behaviour on public transport platforms such as buses and trains. The average accuracy rate of our method is 81% in comparison to 76% by a standard rule-based method.

Video Event Recognition by Dempster-Shafer Theory

This paper presents an event recognition framework, based on Dempster-Shafer theory, that combines evidence of events from low-level computer vision analytics. The proposed method employing evidential network modelling of composite events, is able to represent uncertainty of event output from low level video analysis and infer high level events with semantic meaning along with degrees of belief. The method has been evaluated on videos taken of subjects entering and leaving a seated area. This has relevance to a number of transport scenarios, such as onboard buses and trains, and also in train stations and airports. Recognition results of 78% and 100% for four composite events are encouraging.

Paired associative transcranial alternating current stimulation increases the excitability of corticospinal projections in humans

Many types of non-invasive brain stimulation alter corticospinal excitability (CSE). Paired associative stimulation (PAS) has attracted particular attention as its effects ostensibly adhere to Hebbian principles of neural plasticity. In prototypical form, a single electrical stimulus is directed to a peripheral nerve in close temporal contiguity with transcranial magnetic stimulation delivered to the contralateral primary motor cortex (M1). Repeated pairing of the two discrete stimulus events (i.e. association) over an extended period either increases or decreases the excitability of corticospinal projections from M1, contingent on the interstimulus interval. We studied a novel form of associative stimulation, consisting of brief trains of peripheral afferent stimulation paired with short bursts of high frequency (≥80 Hz) transcranial alternating current stimulation (tACS) over contralateral M1. Elevations in the excitability of corticospinal projections to the forearm were observed for a range of tACS frequency (80, 140 and 250 Hz), current (1, 2 and 3 mA) and duration (500 and 1000 ms) parameters. The effects were at least as reliable as those brought about by PAS or transcranial direct current stimulation. When paired with tACS, muscle tendon vibration also induced elevations of CSE. No such changes were brought about by the tACS or peripheral afferent stimulation alone. In demonstrating that associative effects are expressed when the timing of the peripheral and cortical events is not precisely circumscribed, these findings suggest that multiple cellular pathways may contribute to a long term potentiation-type response. Their relative contributions will differ depending on the nature of the induction protocol that is used.

Generating Isolated Elliptically Polarized Attosecond Pulses Using Bichromatic Counterrotating Circularly Polarized Laser Fields

We theoretically demonstrate the possibility to generate both trains and isolated attosecond pulses with high ellipticity in a practical experimental setup. The scheme uses circularly polarized, counterrotating two-color driving pulses carried at the fundamental and its second harmonic. Using a model Ne atom, we numerically show that highly elliptic attosecond pulses are generated already at the single-atom level. Isolated pulses are produced by using few-cycle drivers with controlled time delay between them.

The challenge of high cube ISO containers for British rail freight operations

Rail freight activity in Britain has increased by almost 50% in the last ten years, with the movement of deep sea ISO containers between ports and inland terminals being a significant growth sector, with considerable further growth potential. High cube ISO containers have become more prevalent, posing a considerable challenge for rail freight operators since much of the rail network has insufficient loading gauge clearance to carry them on standard wagons. This paper investigates the extent to which rail currently handles high cube container movements to/from ports through the analysis of a representative survey of container trains in 2007. The incidence of high cube containers carried by services on gauge-cleared and non-gauge-cleared routes is identified to assess the extent to which a lack of gauge enhancement affects the movement by rail of high cube containers and to identify the impacts of the lack of gauge clearance on operating efficiency. The paper concludes with an evaluation of the likely consequences of the gauge enhancement schemes for which funding is now committed, assessing the extent to which they will reduce or remove the barriers associated with carrying high cube containers between ports and their hinterlands.

An investigation of container train service provision and load factors in Great Britain

The continued growth in the volume of international trade poses considerable economic and sustainability challenges, particularly as transport routes become more congested and concern grows about the role of transport movements in accelerating climate change. Rail freight plays a major role in the inland transport of containers passing through the main British container ports, and potentially could play a more significant role in the future. However, there is little detailed understanding of the nature of this particular rail market, especially in terms its current operating efficiency. This paper examines container train service provision to/from the four main ports, based on analysis of a representative survey of more than 500 container trains between February and August 2007. The extent to which the existing capacity is utilised is presented, and scenarios by which the number of containers carried could be increased without requiring additional train service provision are modelled, to identify the theoretical potential for greater rail volumes. Finally, the paper identifies the challenges involved in achieving higher load factors, emphasising the importance both of wider supply chain considerations and government policy decision-making.

Soluções de transporte ferroviário: simulação de marcha e de tráfego de veículos de tração diesel e elétrica

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica

Transverse Vibrations in Beams Supported by a Piece-Wise Homogeneous Visco- Elastic Foundation

Transversal vibrations induced by a load moving uniformly along an infinite beam resting on a piece-wise homogeneous visco-elastic foundation are studied. Special attention is paid to the additional vibrations, conventionally referred to as transition radiations, which arise as the point load traverses the place of foundation discontinuity. The governing equations of the problem are solved by the normalmode analysis. The solution is expressed in a form of infinite sum of orthogonal natural modes multiplied by the generalized coordinate of displacement. The natural frequencies are obtained numerically exploiting the concept of the global dynamic stiffness matrix. This ensures that the frequencies obtained are exact. The methodology has restrictions neither on velocity nor on damping. The approach looks simple, though, the numerical expression of the results is not straightforward. A general procedure for numerical implementation is presented and verified. To illustrate the utility of the methodology parametric optimization is presented and influence of the load mass is studied. The results obtained have direct application in analysis of railway track vibrations induced by high-speed trains when passing regions with significantly different foundation stiffness.

[Grève des cheminots en Angleterre, train à l'arrêt portant l'inscription LB&SCR, London, Brighton & South Coast Railway] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 56126

[Grève des cheminots en Angleterre, les quais déserts de la gare de Waterloo à Londres] : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 56127