The potential of optical proteomic technologies to individualize prognosis and guide rational treatment for cancer patients

Genomics and proteomics will improve outcome prediction in cancer and have great potential to help in the discovery of unknown mechanisms of metastasis, ripe for therapeutic exploitation. Current methods of prognosis estimation rely on clinical data, anatomical staging and histopathological features. It is hoped that translational genomic and proteomic research will discriminate more accurately than is possible at present between patients with a good prognosis and those who carry a high risk of recurrence. Rational treatments, targeted to the specific molecular pathways of an individual’s high-risk tumor, are at the core of tailored therapy. The aim of targeted oncology is to select the right patient for the right drug at precisely the right point in their cancer journey. Optical proteomics uses advanced optical imaging technologies to quantify the activity states of and associations between signaling proteins by measuring energy transfer between fluorophores attached to specific proteins. Förster resonance energy transfer (FRET) and fluorescence lifetime imaging microscopy (FLIM) assays are suitable for use in cell line models of cancer, fresh human tissues and formalin-fixed paraffin-embedded tissue (FFPE). In animal models, dynamic deep tissue FLIM/FRET imaging of cancer cells in vivo is now also feasible. Analysis of protein expression and post-translational modifications such as phosphorylation and ubiquitination can be performed in cell lines and are remarkably efficiently in cancer tissue samples using tissue microarrays (TMAs). FRET assays can be performed to quantify protein-protein interactions within FFPE tissue, far beyond the spatial resolution conventionally associated with light or confocal laser microscopy. Multivariate optical parameters can be correlated with disease relapse for individual patients. FRET-FLIM assays allow rapid screening of target modifiers using high content drug screens. Specific protein-protein interactions conferring a poor prognosis identified by high content tissue screening will be perturbed with targeted therapeutics. Future targeted drugs will be identified using high content/throughput drug screens that are based on multivariate proteomic assays. Response to therapy at a molecular level can be monitored using these assays while the patient receives treatment: utilizing re-biopsy tumor tissue samples in the neoadjuvant setting or by examining surrogate tissues. These technologies will prove to be both prognostic of risk for individuals when applied to tumor tissue at first diagnosis and predictive of response to specifically selected targeted anticancer drugs. Advanced optical assays have great potential to be translated into real-life benefit for cancer patients

Damage detection and damage evolution monitoring of composite materials for naval applications using acoustic emission testing

Maritime transport has profound importance for the world economy. Vessels of all sizes constantly transport large numbers of passengers and goods across the sea, often under adverse operational conditions. Vessels need to exhibit high levels of reliability, availability, maintainability and safety (RAMS). However, at the same time their performance needs to be optimised ensuring the lowest possible fuel consumption with the maximum operational capacity and range without compromising RAMS. Sweating of naval assets and profitability should be maximised for the operator ensuring investment in future projects and supporting the growth of maritime transport and world economy as a whole. Vessels have been traditionally manufactured using naval steel grades such AH, DH and EH. Smaller leisure and specialised purpose vessels such as patrol boats, etc. have been built using fibre-reinforced composite (FRC) materials. This trend is gradually penetrating the market of larger commercial vessels including freight and cruise ships. However, these are still the early days and further investigation of the optimum FRC manufacturing techniques and mechanical properties together with an in-depth understanding of the damage mechanics are required before such materials can become more commonplace. This project has investigated different glass FRCs using different manufacturing techniques. Glass fibres are preferred due to their lower cost in comparison with carbon fibres. The use of carbon FRCs in maritime applications is limited to the fabrication of racing and high performance speedboat vessels. Samples manufactured under laboratory conditions have been compared with those manufactured by a shipyard. It has been seen that the in-house samples had generally superior performance. Steel-to-composite joints have also been assessed including different designs. The effect of different features in the design such as drilled holes and bolts on the mechanical performance of the manufactured samples has also been evaluated. The damage mechanisms involved during damage propagation and features causing damage initiation have been considered. Damage initiation and subsequent evolution have been monitored using acoustic emission (AE). Various signal processing approaches have been employed (manual and automatic) for optimum evaluation of the AE data obtained in a semiquantitative manner. It has been shown that AE could be applied effectively for structural health monitoring of naval structures in the field. Several factors and parameters that need to be considered during acquisition and analysis have been successfully determined. The key results of the study together with mechanical testing and characterisation of samples employed are presented in summarised form within the present thesis