Advanced Fibre Bragg Grating fabrication systems and devices

This thesis address the creation of fibre Bragg grating based sensors and the fabrication systems which are used to manufacture them. The information is presented primarily with experimental evidence, backed up with the current theoretical concepts. The issues involved in fabricating high quality fibre Bragg gratings are systematically investigated. Sources of errors in the manufacturing processes are detected, analysed and reduced to allow higher quality gratings to be fabricated. The use of chirped Moiré gratings as distributed sensors is explored, the spatial resolution is increased beyond that of any previous work and the use of the gratings as distributed load sensors is also presented. Chirped fibre Bragg gratings are shown to be capable of operating as in-situ wear sensors, capable of accurately measuring the wear or erosion of the surface of a material. Two methods of measuring the wear are compared, giving a comparison between an expensive high resolution method and a cheap lower resolution method. The wear sensor is also shown to be capable of measuring the physical size and location of damage induced on the surface of a material. An array method is demonstrated to provide a high survivability such that the array may be damaged yet operate with minimal degradation in performance.

Liposomes:Formulation and characterisation as contrast agents and as vaccine delivery systems

Liposome systems are well reported for their activity as vaccine adjuvants; however novel lipid-based microbubbles have also been reported to enhance the targeting of antigens into dendritic cells (DCs) in cancer immunotherapy (Suzuki et al 2009). This research initially focused on the formulation of gas-filled lipid coated microbubbles and their potential activation of macrophages using in vitro models. Further studies in the thesis concentrated on aqueous-filled liposomes as vaccine delivery systems. Initial work involved formulating and characterising four different methods of producing lipid-coated microbubbles (sometimes referred to as gas-filled liposomes), by homogenisation, sonication, a gas-releasing chemical reaction and agitation/pressurisation in terms of stability and physico-chemical characteristics. Two of the preparations were tested as pressure probes in MRI studies. The first preparation composed of a standard phospholipid (DSPC) filled with air or nitrogen (N2), whilst in the second method the microbubbles were composed of a fluorinated phospholipid (F-GPC) filled with a fluorocarbon saturated gas. The studies showed that whilst maintaining high sensitivity, a novel contrast agent which allows stable MRI measurements of fluid pressure over time, could be produced using lipid-coated microbubbles. The F-GPC microbubbles were found to withstand pressures up to 2.6 bar with minimal damage as opposed to the DSPC microbubbles, which were damaged at above 1.3 bar. However, it was also found that DSPC-filled with N2 microbubbles were also extremely robust to pressure and their performance was similar to that of F-GPC based microbubbles. Following on from the MRI studies, the DSPC-air and N2 filled lipid-based microbubbles were assessed for their potential activation of macrophages using in vitro models and compared to equivalent aqueous-filled liposomes. The microbubble formulations did not stimulate macrophage uptake, so studies thereafter focused on aqueous-filled liposomes. Further studies concentrated on formulating and characterising, both physico-chemically and immunologically, cationic liposomes based on the potent adjuvant dimethyldioctadecylammonium (DDA) and immunomodulatory trehalose dibehenate (TDB) with the addition of polyethylene glycol (PEG). One of the proposed hypotheses for the mechanism behind the immunostimulatory effect obtained with DDA:TDB is the ‘depot effect’ in which the liposomal carrier helps to retain the antigen at the injection site thereby increasing the time of vaccine exposure to the immune cells. The depot effect has been suggested to be primarily due to their cationic nature. Results reported within this thesis demonstrate that higher levels of PEG i.e. 25 % were able to significantly inhibit the formation of a liposome depot at the injection site and also severely limit the retention of antigen at the site. This therefore resulted in a faster drainage of the liposomes from the site of injection. The versatility of cationic liposomes based on DDA:TDB in combination with different immunostimulatory ligands including, polyinosinic-polycytidylic acid (poly (I:C), TLR 3 ligand), and CpG (TLR 9 ligand) either entrapped within the vesicles or adsorbed onto the liposome surface was investigated for immunogenic capacity as vaccine adjuvants. Small unilamellar (SUV) DDA:TDB vesicles (20-100 nm native size) with protein antigen adsorbed to the vesicle surface were the most potent in inducing both T cell (7-fold increase) and antibody (up to 2 log increase) antigen specific responses. The addition of TLR agonists poly(I:C) and CpG to SUV liposomes had small or no effect on their adjuvanticity. Finally, threitol ceramide (ThrCer), a new mmunostimulatory agent, was incorporated into the bilayers of liposomes composed of DDA or DSPC to investigate the uptake of ThrCer, by dendritic cells (DCs), and presentation on CD1d molecules to invariant natural killer T cells. These systems were prepared both as multilamellar vesicles (MLV) and Small unilamellar (SUV). It was demonstrated that the IFN-g secretion was higher for DDA SUV liposome formulation (p<0.05), suggesting that ThrCer encapsulation in this liposome formulation resulted in a higher uptake by DCs.

Using process-oriented holonic (PrOH) modelling to increase understanding of information systems

Methodologies for understanding business processes and their information systems (IS) are often criticized, either for being too imprecise and philosophical (a criticism often levied at softer methodologies) or too hierarchical and mechanistic (levied at harder methodologies). The process-oriented holonic modelling methodology combines aspects of softer and harder approaches to aid modellers in designing business processes and associated IS. The methodology uses holistic thinking and a construct known as the holon to build process descriptions into a set of models known as a holarchy. This paper describes the methodology through an action research case study based in a large design and manufacturing organization. The scientific contribution is a methodology for analysing business processes in environments that are characterized by high complexity, low volume and high variety where there are minimal repeated learning opportunities, such as large IS development projects. The practical deliverables from the project gave IS and business process improvements for the case study company.