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The performance of switches and crossings compared with plain line is complicated by the presence of movable parts, changing rail geometry and non-uniformities in the composite and/or trackbed stiffness. These features lead to complex vehicle–track interactions and higher maintenance costs. The trackbed stiffness is the least well-controlled engineering property. A greater variability in trackbed stiffness leads to higher differential trackbed settlement and associated poorer track quality. At switches and crossings, changes in trackbed stiffness are exacerbated by changing rail properties which also contribute to changes in the overall composite track stiffness. This work focuses on the role of variations in stiffness on the performance of switches and crossings. Field measurements of bearer displacement were carried out using geophones at a switch and crossing equipped with under sleeper pads. The vehicle–switch and crossing interaction was modelled using a multi-body system and finite element method. The trackbed stiffness along the whole of the switch and crossing was inferred using the measurements of track deflections in an iterative back-calculation taking account of changing rail properties. It is shown that not including the variation in trackbed/composite stiffness leads to significant under/overestimates of the wheel–rail contact forces. Under sleeper pads are shown to reduce absolute maximum loads, but may increase the variation in deflection.

The protein toxin restrictocin, isolated from the mould Aspergillus restrictus, inactivates protein synthesis in eukaryotic cells by blocking the ribosome elongation cycle. This protein acts as a specific nuclease that cuts off a small fragment from the 28-S rRNA. Biochemical and biological characterization of this toxin indicated that it is a non-glycosylated polypeptide of M , 16836, exhibiting in cell-free systems a protein synthesis inhibition capacity similar to that of the ricin A chain. This polypeptide seemed unable to penetrate most of the cancer cell lines tested, as measured by its low in vitro cytotoxicity. In addition in vivo studies in BALB/c mice demonstrated that restrictocin toxicity was very low and that in rabbits, after intravenous injection 15% of the toxin was still present in the blood stream 24 h later.After derivatization with N-succinimidyl 3-(2-pyridyldithio)propionate and reduction by dithiothreitol, the restrictocin maintained its protein synthesis inhibitory activity, as assayed in a cell-free system. This derivatized toxin was then coupled to monoclonal antibodies (MBrl, MLuC1, MLuC2, MOv17, MOv18, MOv19) which exhibited a restricted spectrum of reactivity against human carcinomas. The biochemical and biological characterization of the immunoconjugates indicated that (a) when restrictocin was coupled to monoclonal antibodies with an average molar ratio of about 2, the immunoconjugates maintained the binding activity of the antibody and protein synthesis inhibition activity of the toxin; (b) four immunoconjugates were tested for cytotoxicity and three of them obtained with the MBrl, MLuCl and MOvl7 monoclonal antibodies exhibited a good level of cytotoxicity for relevant target cells and low or no toxicity for the irrelevant cell lines. The MLuC2 monoclonal antibody which gave rise to a completely ineffective immunoconjugate, induced internalization of less than one tenth of the antigenic sites whereas the MBrl, MLuCl and MOv17 monoclonal antibodies exhibited about one third of the antigenic sites internalized. From these data it is concluded that, providing an appropriate target antigen and coupling procedure are selected, restrictocin can be considered a suitable toxin for immunoconjugate generation.

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This paper describes a wildfire forecasting application based on a 3D virtual environment and a fire simulation engine. A novel open source framework is presented for the development of 3D graphics applications over large geographic areas, offering high performance 3D visualization and powerful interaction tools for the Geographic Information Systems (GIS) community. formation. The user is enabled to simulate and visualize a wildfire spreading on the terrain integrating spatial information on topography and vegetation types with weather and wind data. The application communicates with a remote web service that is in charge of the simulation task. The user may specify several parameters through a friendly interface before the application sends the information to the remote server responsible of carrying out the wildfire forecasting using the FARSITE simulation model. During the process, the server connects to different external resources to obtain up-todate meteorological data. The client application implements a realistic 3Dvisualization of the fire evolution on the landscape. A Level Of Detail (LOD) strategy contributes to improve the performance of the visualization system.

We studied the effect of intracerebroventricular infusion of dopamine and dopamine agonists in rat and pnmate models of Parkinson's disease as an experimental approach to the treatment of levodopa-induced fluctuations. The infusion of dopamine, lisuride, and pergolide into the ventricle ipsilateral to the lesion, by bhydroxydopamine, of the nigrostriatal pathway induced a contralateral rotation which was maximal 24-48 h after infusion and whose intensity progressively decreased over the period of 1 week. PHISpiperone binding was decreased by the infusion of dopamine but the responses to subcutaneous apomomorphine were unchanged. The infusion of dopamine also restored the levels of monoamines in the rat brain. In chronic reserpized rats, the infusion of dopamine restored brain levels of dopamine but did not reverse akinesia unless monoamine oxidase inhibitors were simultaneously administered, either systemically or intracerebroventricularly Lisuride and pergolide proved much weaker than dopamine in reversing the effects of reserpine. Intracerebroventricular infusion of dopamine plus deprenyl reversed MPTP induced akinesia in monkeys but the pump used for the delivery was not well tolerated, because of its size, by the animals.

Inhibition of nitric oxide synthesis during a severe low output state in sheep is associated with a better hemodynamic response, as evidenced by a greater vasoconstriction, and signs of less marked tissue hypoxia. It is likely that inhibition of nitric oxide synthesis in this model leads to an imbalance between the tonic relaxing action of nitric oxide and the influences of vasoconstrictor agents.