Cell surface chondroitin sulfate proteoglycans in tumor cell adhesion, motility and invasion

Genes that encode enzymes that convert inactive "prodrugs" into anticancer metabolites may be therapeutically useful against brain tumors. Unlike other genes tested to date in brain tumor models, the Escherichia coli gpt gene is unique in that it not only sensitizes cells to the prodrug 6-thioxanthine (6TX) but also encodes resistance to a different regimen (mycophenolic acid, xanthine, and hypoxanthine), thus providing a means to select for gpt-positive cells. In the present study, rat C6 glioma cells were infected with a retrovirus vector that transduces this gene. A clonal line (C6GPT-7) was derived that exhibited significant 6TX susceptibility in vitro with an ID50 of 2.5 mumol/L, whereas 50% growth inhibition of parental C6 cells was not achieved at concentrations tested (up to 50 mumol/L). This line also exhibited significant sensitivity to 6-thioguanine (6TG), with an ID50 of 0.05 mumol/L, whereas 50% growth inhibition of parental C6 cells was achieved at 0.5 mumol/L. In a "bystander" assay, C6GPT-7 tumor cells efficiently transferred 6TX sensitivity to C6 cells at ratios as low as 1:9 (C6GPT-7:C6). This in vitro bystander effect was abrogated when C6GPT-7 and C6 cells were separated by a microporous membrane, suggesting that it was not mediated by highly diffusible metabolites. In vivo both 6TX and 6TG significantly inhibited the growth of subcutaneously transplanted C6GPT-7 cells but not that of C6 cells in athymic mice. In an intracerebral model, both 6TX and 6TG exhibited significant antiproliferative effects against tumors formed by C6GPT-7 cells. These findings provide a basis for exploring further gene therapy strategies based on in vivo transfer of the E coli gpt gene to provide chemosensitivity against 6TX and 6TG.     

Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide

A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.     

Zinc-sulphate-heptahydrate coated activated carbon for microbe removal from stormwater

There is a need to develop effective stormwater filters for passive (without any addition of chemicals or energy) and effective removal of pathogens in order to mainstream stormwater harvesting. This study focuses on the development of coated granular activated carbon (GAC) filtration material in order to develop filters for effective removal of pathogens from urban stormwater. Several laboratory trials were performed to gauge the effectiveness of the filters, which use a mixture of the zinc-sulphate-heptahydrate coated GAC and sand, on the removal of Escherichia coli (E. coli) from semi-natural stormwater. On average, a 98% removal of the inflow concentration of E. coli was achieved. Furthermore, there was also an improvement of approximately 25% in the removal of phosphorous. However, it was found that the treated material was leaching zinc. It was important to determine whether the observed removal of E. coli was indirectly caused by the sampling methodology. The results showed that the inactivation of the E. coli in the collected sample was small compared with the inactivation which actually occurred within the filter. This provides much promise to the filter, but the presence of zinc in the outflow demonstrates the need for further investigation into the stabilisation of the coating process.     

Automated image analysis of Euglena gracilis Klebs (Euglenophyta) for measuring sublethal effects of three model contaminants

The short-term impacts of atrazine (herbicide), tributyltin (organometal) and copper on the behaviour of Euglena gracilis Klebs (Euglenophyta) were assessed. First, the ECOTOX automated image analysis system was used, which measured swimming velocity, cell shape, percentage of cells swimming upwards, and randomness of swimming. Next, visual observation by microscopy was used to measure percentage of cell motility and cell shape. Behavioural changes can be used as an indicator of stress in less than 24 h, potentially making them suitable for inclusion in early-warning systems for water quality. Findings indicate that E. gracilis is a very sensitive organism to copper, showing inhibition of motility with visual observation at 0.8 μmol/L within 1 h. The image analysis system was in general less sensitive than visual observation for detecting behavioural changes after incubation in copper. In contrast, after exposure to organic contaminants atrazine and tributyltin, the ECOTOX system detected small changes in the number of cells swimming upwards (antigravitactic behaviour) at higher concentrations.     

Modelling of Bird Strike on an Aircraft Wing Leading Edge Made from Fibre Metal Laminates – Part 2: Modelling of Impact with SPH Bird Model

Fibre Metal Laminates with layers of aluminium alloy and high strength glass fibre composite have been reported to possess excellent impact properties and be suitable for aircraft parts likely to be subjected to impacts such as runway debris or bird strikes. In a collaborative research project, aircraft wing leading edge structures with a glass-based FML skin have been designed, built, and subjected to bird strike tests that have been modelled with finite element analysis. In this second part of a two-part paper, a finite element model is developed for simulating the bird strike tests, using Smooth Particle Hydrodynamics (SPH) for modelling the bird and the material model developed in Part 1 of the paper for modelling the leading edge skin. The bird parameters are obtained from a system identification analysis of strikes on flat plates. Pre-test simulations correctly predicted that the bird did not penetrate the leading edge skin, and correctly forecast that one FML lay-up would deform more than the other. Post test simulations included a model of the structure supporting the test article, and the predicted loads transferred to the supporting structure were in good agreement with the experimental values. The SPH bird model showed no signs of instability and correctly modelled the break-up of the bird into particles. The rivets connecting the skin to the ribs were found to have a profound effect on the performance of the structure.     

Seat belt usage rates: a test of Peltzman's hypothesis

Despite the universally accepted belief that the use of seat belts would have a significant impact upon the number of vehicular fatalities, current evidence indicates that relatively few drivers employ their seat belts. Various hypotheses have been offered to explain this phenomenon, many of which conclude that a driver's decision to use a seat belt is independent of the risk experienced in his trip making. This paper develops an economic model which focuses upon the relationship between driver use of seat belts and the travel conditions under which trips are made. Using data obtained from a national survey of households, a binary logit model is developed to test the hypothesis that seat belt usage is influenced by the level of risk experienced in one's trip making. The estimation results were consistent with the underlying hypothesis that individuals travelling in more risky environments are more likely to use their seat belts. The econometric results are then employed to examine various policy issues, including the predicted use of seat belts for population sub-groups, driver response to the introduction of a small urban car, and the impact upon the probability of a fatality resulting from vehicle fleet downsizing.     

Investigation of composite ☐ beam dynamics using a higher-order theory

A higher-order composite ☐ beam theory is developed to model beams with arbitrary wall thicknesses. The theory, which is based on a refined displacement field, approximates the three-dimensional elasticity solution so that the beam cross-sectional properties are not reduced to one-dimensional beam parameters. Both inplane and out-of-plane warping are included automatically in the formulation. The model can accurately capture the tranverse shear stresses through the thickness of each wall while satisfying stress-free boundary conditions on the inner and outer surfaces of the beam. Numerical results are presented for beams with varying wall thicknesses and aspect ratios. The static results are correlated with available experimental data and show excellent agreement. Dynamic results presented show the importance of including inplane and out-of-plane warping deformations in the formulation.