No description available.

No description available.

No description available.

No description available.

No description available.

Malignant melanoma is an immunogenic tumour capable of inducing a humoral immune response, as shown by tumour-reactive serum antibody in patients. Lack of effective chemotherapy in association with the immunogenic nature of the malignancy, has stimulated interest in the immunological management of the malignancy by antibody. Many mouse monoclonal antibodies against melanoma antigens have been developed, and some have been shown to induce tumour regression. However, a limitation on the use of mouse monoclonal antibodies in patients is the induction of an immune response against the immunising xenogeneic protein. The employment of human monoclonal antibodies, may be expected to reduce the patient's immune response against the allogeneic protein. Although more difficult to produce than mouse monoclonal antibodies, several human monoclonal antibodies have been established which induce tumour regression. Here I describe the establishment of mouse/human heterohybridomas producing human monoclonal antibody, from tumour-draining lymph nodes. A series of novel assay systems, initially developed and characterised using melanoma reactive mouse monoclonal antibodies, were sequentially employed for the selection of human antibody exhibiting high tumour specificity. Several clones producing melanoma reactive human antibody were established. Clone MDT. 1 was selected for further characterisation, because of its highly selective reactivity against viable melanoma and other neuroectodermal cell lines, but lack of reactivity against other common malignant and non-malignant cell lines. Such restricted cell reactivity is characteristic of reactivity with class 2 tumour associated antigens. MDT. 1 was shown, in ELISA, to exhibit reactivity to ganglioside antigens GD3, GD2, GD1b, GM3 and GM2. These antigens are commonly associatedw ith the malignant transformation of melanocytes and other neuroectodermal cells. Enzymatic modification of GM3, with neuraminidase, identified the reactive minimal essential epitope as Neua2- 3Galß1-4GIc-. Reactivity with rat monoclonal antibody 9G4 and molecular analysis showed MDT. 1 is encoded by the highly conserved VH4 gene, VH4-21. Like other VH4-21 encoded autoantibodies MDT. 1 exhibits reactivity with the cold agglutinin T. Analysis of the structures of `i' and sialogangliosides has identified similar structural epitopes, which may confer MDT. 1 reactivity. VH4-21 encoded autoantibody 216 exhibits similar reactivity with tumour associated ganglioside antigens as MDT. 1. Sialo-ganglioside/`i' reactive VH4-21 encoded antibodies, could therefore represent an important aspect of autoantibodies in the overall host immune response to tumour.

No description available.

The prescription and use of Assistive Technology, particularly teleprostheses, may be enhanced by the use of standard assessment techniques. For input devices, in particular, existing assessment studies, most of which are based on Fitts' Law, have produced contradictory results. This thesis has made contributions to these and related fields, particularly in the following four areas. Fitts' Law (and background information theory) is examined. The inability of this paradigm to match experimental results is noted and explained. Following a review of the contributing fields, a new method of assessing input devices is proposed, based on Fitts' Law, classical control and the concept of 'profiling'. To determine the suitability of the proposed method, it is applied to the results of over 2000 trials. The resulting analysis emphasises the importance of interaction effects and their influence on general comparison techniques for input devices. The process of verification has highlighted gain susceptability as a performance criterion which reflects user susceptability; a technique which may be particularly applicable to Assistive Technology.

No description available.

Many industrial fermentations use complex medium containing both carbohydrate and oils as their carbon sources. Oil supplements have been shown to increase the antibiotic titre and are a cheaper alternative carbon source, in terms of carbon per unit volume, when compared to carbohydrates. Oil supplements are also preferred on an energy supply basis and have natural antifoam properties. The major disadvantage to the use of oils in process media is the level of oil remaining at the end of the fermentation. Research has been undertaken to examine the effects of process variables on lipid utilisation and residual oil levels in 5 litre batch fermentations of Streptomyces clavuligerus. The project illustrates the way in which both the chemical environment, media composition and method of pH control, and the physical environment, such as agitation rate and particle size, may influence growth, lipase activity, lipid utilisation and secondary metabolite production. Changes in carbon source influenced growth and productivity. Addition of rapeseed oil increased final product titres by approximately 900%. The type and concentration of the nitrogen source was found to influence maximum lipase activity and initial oil utilisation rates. Media composition and pH control experiments had little effect on residual oil levels. A gas chromatography method was developed in order to analyse the changes in the composition of oil during fermentation. Derivatisation of the fatty acids by methylation was successful and revealed that the composition of residual oil was similar to that of the initial rapeseed oil added. There was no indicated specificity in the utilisation of any individual fatty acids of rapeseed oil. Increasing tip speed in the fermentation process from 1 .88m s^[-1] to 2.83 m s^[-1] increased maximum biomass levels, decreased lipase activity and did not affect clavulanic acid production. A tip speed of 3.77m s^[-1] was detrimental to growth, increasing hyphal fragmentation, and decreased lipase activity. Increasing constant tip speed did not reduce residual oil levels. Antibiotic titres were relatively unaffected by changes in tip speed. Addition of a surfactant to the complex medium, in order to facilitate oil droplet breakage and hence increase oil utilisation, was investigated. Addition of the surfactant decreased residual oil levels with an observed increase in final clavulanic acid titres. This research has shown the effect of some chemical and physical parameters on lipid utilisation and clavulanic acid production in the 5 litre batch fermentation of S. clavuligerus. Lipid utilisation could not be enhanced by increasing lipase activity or varying media composition and agitation rates. Addition of surfactant to the process media significantly reduced residual oil levels. This approach may have potential as a generic method of reducing residual oil levels and enhancing secondary metabolite titres in industrial processes using lipid based medium.