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The development of time-dependent biofouling model for ships
Despite a large amount of research, the effect of barnacle fouling on the frictional resistance has a lack of systematical experimental investigation focussing on parameters such as size, coverage area and settlement pattern. Limited roughness functions data about barnacle fouling is available in the literature. Moreover, although a large number of the study has been carried out on the effect of roughness on the frictional resistance, only the limited lab-based results were extrapolated to the full-scale ship results (Schultz et al.,2011).;In addition, antifouling precautions cost 5% of the total fuel-oil cost of world fleet for a year, and to the best of the author's knowledge, there is no scientifically settled approach for selecting the best antifouling coating for the ship in question. This situation forced vessel owners/responsible person have their particular strategy to deal with marine fouling based on personal experience or negotiating with the sales personnel of the paint company.;Based on the background given above, an extensive and systematic experimental study was carried out for investigating the effect of barnacle fouling on ship resistance and powering. One of the most common barnacle geometry was produced on bundles through a 3D technology and attached on the flat plates for towing tank experiments at Kelvin Hydrodynamics Laboratory in the University of Strathclyde. Eighteen different configurations varying in terms of size, coverage area and settlement pattern were tested. Drag characterisations, determination of roughness functions and full-scale extrapolations were performed.;A simplified time-dependent biofouling prediction model for ships was developed in order to be used as a decision support tool, regarding the effect of biofouling on ship resistance due to the performance of the antifouling coating. First, a growth prediction model was developed based on the antifouling field test data (fouling ratings in time) and then time parameter of this model was assigned to the idle times of ships coming from ship operational data. The fouling ratings were predicted in time according to this data, and then these fouling ratings were converted into the sand roughness height in accordance with the roughness data provided in the literature and this PhD thesis. Predicted equivalent sand roughness heights were then employed in the Granville similarity law scaling process to predict the increase in the ship frictional resistance and powering. Finally, the results were compared with real-world operation data and ship performance report provided by a ship performance analysis company. The results of the comparison showed that there is a good agreement between the predictions and real-world operation data as well as the company report.Despite a large amount of research, the effect of barnacle fouling on the frictional resistance has a lack of systematical experimental investigation focussing on parameters such as size, coverage area and settlement pattern. Limited roughness functions data about barnacle fouling is available in the literature. Moreover, although a large number of the study has been carried out on the effect of roughness on the frictional resistance, only the limited lab-based results were extrapolated to the full-scale ship results (Schultz et al.,2011).;In addition, antifouling precautions cost 5% of the total fuel-oil cost of world fleet for a year, and to the best of the author's knowledge, there is no scientifically settled approach for selecting the best antifouling coating for the ship in question. This situation forced vessel owners/responsible person have their particular strategy to deal with marine fouling based on personal experience or negotiating with the sales personnel of the paint company.;Based on the background given above, an extensive and systematic experimental study was carried out for investigating the effect of barnacle fouling on ship resistance and powering. One of the most common barnacle geometry was produced on bundles through a 3D technology and attached on the flat plates for towing tank experiments at Kelvin Hydrodynamics Laboratory in the University of Strathclyde. Eighteen different configurations varying in terms of size, coverage area and settlement pattern were tested. Drag characterisations, determination of roughness functions and full-scale extrapolations were performed.;A simplified time-dependent biofouling prediction model for ships was developed in order to be used as a decision support tool, regarding the effect of biofouling on ship resistance due to the performance of the antifouling coating. First, a growth prediction model was developed based on the antifouling field test data (fouling ratings in time) and then time parameter of this model was assigned to the idle times of ships coming from ship operational data. The fouling ratings were predicted in time according to this data, and then these fouling ratings were converted into the sand roughness height in accordance with the roughness data provided in the literature and this PhD thesis. Predicted equivalent sand roughness heights were then employed in the Granville similarity law scaling process to predict the increase in the ship frictional resistance and powering. Finally, the results were compared with real-world operation data and ship performance report provided by a ship performance analysis company. The results of the comparison showed that there is a good agreement between the predictions and real-world operation data as well as the company report
Methods of in-situ monitoring of suspension polymerisation for process understanding and optimisation
Increasing Environmental and Health and Safety regulations mean that the demands for cost-effective, accurate and information-rich methods of process analysis are increasing exponentially. This project aimed to evaluate the use of technologies – Raman and Acoustic Emission Spectroscopies – coupled with a variety of multivariate analysis tools to provide a framework for the optimisation of polystyrene suspension polymerisation, allowing industrial partners to monitor the reaction progression, determine particle size information and unreacted monomer concentration. Spectral data collected during a series of lab-scale polymerisation reactions and basic model mixtures was used to determine the effectiveness of each method – including the use of a variety of probe configurations for Raman analysis. The data was treated with established pre-treatment methods (Savitzky-Golay filtering, SNV transformation and EMSC) and a novel method (OPLECm) to enhance the performance of mathematical models and investigate the effectiveness of the methods for this application.The results indicate that Raman and Acoustic Emission spectroscopies can provide monomer concentration and particle size information for this reaction, respectively. Offline Raman data is shown to be approximately 33% less variable than current offline HPLC methods, and in-situ analysis showing qualitatively similar results to offline gravimetric determination of residual monomer. Furthermore, the potential benefit of increasing laser diameter is shown. The pre-treatment of this data prior to modelling shows Savitzky-Golay derivatisation to provide the least improvement (11.4% RMSEp); with SNV, EMSC and OPLECm performing similarly (4.1, 3.8 and 4.1% respectively). Models built with EMSC and OPLECm pre-treatment provide best results overall, with just 4 and 3 latent variables, respectively. Finally, Acoustic Emission spectroscopy provided data which showed good correlation to offline sieving analysis, indicating a strong potential for its use in PSD determination during this reaction.Increasing Environmental and Health and Safety regulations mean that the demands for cost-effective, accurate and information-rich methods of process analysis are increasing exponentially. This project aimed to evaluate the use of technologies – Raman and Acoustic Emission Spectroscopies – coupled with a variety of multivariate analysis tools to provide a framework for the optimisation of polystyrene suspension polymerisation, allowing industrial partners to monitor the reaction progression, determine particle size information and unreacted monomer concentration. Spectral data collected during a series of lab-scale polymerisation reactions and basic model mixtures was used to determine the effectiveness of each method – including the use of a variety of probe configurations for Raman analysis. The data was treated with established pre-treatment methods (Savitzky-Golay filtering, SNV transformation and EMSC) and a novel method (OPLECm) to enhance the performance of mathematical models and investigate the effectiveness of the methods for this application.The results indicate that Raman and Acoustic Emission spectroscopies can provide monomer concentration and particle size information for this reaction, respectively. Offline Raman data is shown to be approximately 33% less variable than current offline HPLC methods, and in-situ analysis showing qualitatively similar results to offline gravimetric determination of residual monomer. Furthermore, the potential benefit of increasing laser diameter is shown. The pre-treatment of this data prior to modelling shows Savitzky-Golay derivatisation to provide the least improvement (11.4% RMSEp); with SNV, EMSC and OPLECm performing similarly (4.1, 3.8 and 4.1% respectively). Models built with EMSC and OPLECm pre-treatment provide best results overall, with just 4 and 3 latent variables, respectively. Finally, Acoustic Emission spectroscopy provided data which showed good correlation to offline sieving analysis, indicating a strong potential for its use in PSD determination during this reaction
Targeted of cannabinoids in hair and androgens in saliva and untargeted profiling of the effects of exercise
The thesis is made up of four chapters. The first chapter is the general introduction to prepare biological samples for analysis, including extraction methods, derivatization and LC-MS instrumentation, including separation techniques. In addition, description of metabolomics approaches which are deployed in order to determine and/or quantify any changes to the metabolites which occur within a biological system in response to different stimuli such as diet, lifestyle and physical activity. The second chapter describes the quantification of cannabinoids in human hair through derivatization and liquid chromatography-tandem mass spectrometry. Cannabinol (CBN), Δ9-Tetrahydrocannabinol (THC) and its main metabolite 11nor-Δ9- Tetrahydrocannabinol carboxylic acid (THC-COOH) which are the most popular indicators of cannabis use. The use of this drug is widespread around the world and causes a serious social and health problems. In this study, a method based on solid-phase extraction (SPE) and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was developed and validated. In this procedure, hair samples were extracted and derivatized with 2fluoro-1-methyl pyridinium-p-toluenesulfonate (FMP-TS) before injecting into the LC-MS-MS. The method showed excellent linearity with a coefficient of determination (r2) better than 0.99 for the analytes of interest. The extractionrecovery was between 81% and 105 % for all compounds. The limit of detection (LOD) and quantification (LOQ) were 2 and 20 pg/mg respectively for both CBN and THC and was 0.1 and 0.2 pg/mg for THC-COOH. Intra- and inter-assay precision were always lower than 4% and 11%, respectively, for these cannabinoids. Whereas the intra- and inter-assay bias were between (14% and 18 %) and (15 and -12 %), respectively.;Twenty-seven hair specimens from cannabis consumers were investigated using the optimized and validated method. Ultimately, CBN and THC were detected in all specimens, whereas THC-COOH was quantified in 13 specimens. Unlike CBN and THC, THC-COOH was semi-quantifiable (all values less than the limit of quantification (LOQ), but more than the limit of detection (LOD)) in 3 samples and was not detected in 11 samples. The levels of CBN, THC and THC-COOH on average were (0.022-2.562 ng/mg), (0.049-0.431 ng/mg) and (0.222-4.867 pg/mg) respectively. The median levels were (0.054 ng/mg), (0.087 ng/mg) and (0.34 pg/mg) for CBN, THC and THC-COOH respectively. Detection at least of THCCOOH metabolite in hair, especially in routine work seems to be compulsory in addition to THC and other main cannabinoids in order to distinguish between active ingestion and passive exposure.;In the last decade, high-performance liquid chromatography/tandem mass spectrometry (LC/MS/MS) combined with electrospray ionization (ESI) has beenwidely used for determining low concentrations of steroids, and derivatization has often been employed to enhance detection. The third chapter describes the development of a derivatization method for quantification of testosterone and dehydroepiandrosterone in saliva samples from young professional soccer players, pre- and post-Training, using tandem mass spectrometry. In the present study, endogenous steroids were extracted using a Strata-XL polymeric reversephase cartridge. The isolated steroids were reacted with 2-hydrazino-1- methylpyridine (HMP). A liquid chromatography-tandem mass spectrometry (LCMS/MS) was used in a positive mode with multiple reaction monitoring (MRM) for the quantification of testosterone (T) and its biosynthetic precursor, dehydroepiandrosterone (DHEA), in saliva samples collected from twenty young Saudi professional soccer players. The extraction recovery during the pretreatment was >89% and gave 89% and gave <±20% for inter- and intra-assay precision and accuracy. The limits of quantification (LOQ) were found to be 20 pg/mL for (T and DHEA) and 50 pg/mL for Epitestosterone (EPI). The results showed no significant variation in the concentration of T between pre and post-training, whereas DHEA was significantly increased after short-term exercise. EPI could not be detected in the saliva samples.;The fourth chapter is about metabolomics profiling of plasma, urine and saliva after short-term training in young professional football players in Saudi Arabia.Urine, plasma and saliva were collected on two days pre- and post-training. An Orbitrap Exactive mass spectrometer was used to analyse the samples. A reversed-phase (RP) column was used for the analysis of nonpolar plasma components, and a ZICpHILIC column was used for the analysis of polar metabolites in plasma, saliva and urine. There was no marked variation in the metabolite profiles between pre day1 and 2 nor between post day1 and 2 according to principal components analysis (PCA). When orthogonal partial least squares (OPLS-DA) modelling was used then the models separating pre- and posttraining samples could be fitted based on the total number of significant metabolites 75, 16 and 32 for urine, plasma and saliva using hydrophilic interaction chromatography (HILIC) and 6 for plasma analysed on a reversedphase (RP) column respectively
Development of a cell encapsulation technology for the production of functional, micro-encapsulated pancreatic islets for transplantation
Previously held under moratorium from 8 August 2019 until 9 December 2021Diabetes type 1 is an autoimmune disease in which the patient’s own immune systemdestroys the insulin producing β-cells, located in the pancreatic islets. Without enough insulinproduction, the blood glucose levels of the patient rise, which can lead to damages of bloodvessels and nerves, blindness or even seizures and comas. For some patients that havetrouble maintaining normoglycaemia allogeneic islet transplantation has become analternative treatment option. Patients with these transplanted islets are no longer prone tohypoglycaemic episodes and can sometimes become completely insulin independent.However, this success is not long-lived. The life span of the transplanted islets is limited dueto the host’s immune responses and the toxicity of modern immunosuppressive agents. Inthis thesis, islet encapsulation for clinical transplantation is investigated and furtherdeveloped. Islet encapsulation can protect the islets from the immune system, without theaid of the immunosuppressants. The construction and optimization of a micro-encapsulatorthat can be used to create encapsulations is described, as well as the multiple parameters tocreate small, uniform encapsulations. To further enhance the biocompatibility andimmunoprotective properties of alginate hydrogel, alginate was purified to eliminate mostof the impurities and tested for its permeability. Encapsulating pancreatic islets in thispurified alginate showed encouraging results, with the islets remaining viable and functionallonger than their control counterparts. Larger islets can develop necrotic cores withinencapsulations, due to the lack of vascularization. To create smaller islets out of dissociatedlarger islets, a single-step encapsulation and aggregation method was developed, thatunfortunately was not suitable for islet cells, but was capable of developing functionalhepatic organoids out of HepaRG cells, that could be used for drug testing. Finally, a proof ofprinciple was given for the creation of pancreatic islet patches using 3D bioprinting methods.Diabetes type 1 is an autoimmune disease in which the patient’s own immune systemdestroys the insulin producing β-cells, located in the pancreatic islets. Without enough insulinproduction, the blood glucose levels of the patient rise, which can lead to damages of bloodvessels and nerves, blindness or even seizures and comas. For some patients that havetrouble maintaining normoglycaemia allogeneic islet transplantation has become analternative treatment option. Patients with these transplanted islets are no longer prone tohypoglycaemic episodes and can sometimes become completely insulin independent.However, this success is not long-lived. The life span of the transplanted islets is limited dueto the host’s immune responses and the toxicity of modern immunosuppressive agents. Inthis thesis, islet encapsulation for clinical transplantation is investigated and furtherdeveloped. Islet encapsulation can protect the islets from the immune system, without theaid of the immunosuppressants. The construction and optimization of a micro-encapsulatorthat can be used to create encapsulations is described, as well as the multiple parameters tocreate small, uniform encapsulations. To further enhance the biocompatibility andimmunoprotective properties of alginate hydrogel, alginate was purified to eliminate mostof the impurities and tested for its permeability. Encapsulating pancreatic islets in thispurified alginate showed encouraging results, with the islets remaining viable and functionallonger than their control counterparts. Larger islets can develop necrotic cores withinencapsulations, due to the lack of vascularization. To create smaller islets out of dissociatedlarger islets, a single-step encapsulation and aggregation method was developed, thatunfortunately was not suitable for islet cells, but was capable of developing functionalhepatic organoids out of HepaRG cells, that could be used for drug testing. Finally, a proof ofprinciple was given for the creation of pancreatic islet patches using 3D bioprinting methods
Order and construction in Christopher Alexander, exploring the living building process
The research tackles the crisis of architecture in its two main areas of operation: education and profession. It starts with identifying the themes of the crisis and it first causes, which are found in the separation of the self from the outer world, a defining character of modernity. It then progresses to uncovering the most important manifestations of such separation in everyday design practice, to focus on reintegrating the self in a different design process.The researcher is guided in this voyage by a profound exploration of Christopher Alexander's work, conducted with Alexander himself, his wife and co-author Maggie Moore Alexander, and his inner circle of life-long collaborators. From Alexander, the research embarked in short extra-disciplinary explorations in areas such as psychomotricity, art-therapy and disciplines of the body-mind. The method is however far from pure secondary investigation. The research starts from practice to distill the questions that the literature review is called to help answering, in a proper Project-Based Learning approach. The backbone of the research is in fact four real-world projects undertaken both in educational and professional contexts. Located in a sequence of successive experiences, each of these projects led to the definition of a "model process" of design, which allowed to systematize and enrich, step-by-step, a consistent body of knowledge based on actual practice. Eventually, the research comes to formalize a "final" model-process around the for basic modules of "Land Exploration", "Pattern Language", "Composition" and "Conception and Construction", with a clear understanding that such synthesis is "final"only as long as the PhD study is concerned, but it is essentially one of the many steps of an "unfolding" pathway towards the radical refoundation of architectural practice in the XXIst century.The research tackles the crisis of architecture in its two main areas of operation: education and profession. It starts with identifying the themes of the crisis and it first causes, which are found in the separation of the self from the outer world, a defining character of modernity. It then progresses to uncovering the most important manifestations of such separation in everyday design practice, to focus on reintegrating the self in a different design process.The researcher is guided in this voyage by a profound exploration of Christopher Alexander's work, conducted with Alexander himself, his wife and co-author Maggie Moore Alexander, and his inner circle of life-long collaborators. From Alexander, the research embarked in short extra-disciplinary explorations in areas such as psychomotricity, art-therapy and disciplines of the body-mind. The method is however far from pure secondary investigation. The research starts from practice to distill the questions that the literature review is called to help answering, in a proper Project-Based Learning approach. The backbone of the research is in fact four real-world projects undertaken both in educational and professional contexts. Located in a sequence of successive experiences, each of these projects led to the definition of a "model process" of design, which allowed to systematize and enrich, step-by-step, a consistent body of knowledge based on actual practice. Eventually, the research comes to formalize a "final" model-process around the for basic modules of "Land Exploration", "Pattern Language", "Composition" and "Conception and Construction", with a clear understanding that such synthesis is "final"only as long as the PhD study is concerned, but it is essentially one of the many steps of an "unfolding" pathway towards the radical refoundation of architectural practice in the XXIst century
The application of metabolomics in human health and disease
Metabolomics remains one of the rapidly growing tools for the identification of new disease diagnostic biomarkers. Mass spectrometry (MS) coupled to a liquid chromatographic (LC) system and nuclear magnetic resonance (NMR) are the two major analytical plaforms currently employed in metabolomic profiling studies of complex biofluid samples. However, due to its inherent higher sensitivity and fast data acquisition, MS remains one of the most dominant analytical techniques used in metabolomics. In this project, metabolomics was employed in various studies to assess metabolite biomarkers associated with health and disease. All the studies employed liquid chromatography-mass spectrometry (LC-MS) on an Orbitrap Exactive mass analyser, andusing ZIC-pHILIC or/and C18 analytical columns. Data was acquired using XCalibur software and metabolite identification was ascertained based on accurate mass detection, retention time comparisons with authentic external standards, and database searching. The acquired data was analysed using both unsupervised (PCA-X) and supervised (OPLS-DA) models in SIMCA in order to determine discriminating metabolite biomarkers responsible for the observed clustering patterns. Investigation of metabolomic effects of an 80 km ultramarathon exercise among healthy volunteers on a treadmill gave clear separation between the pre- and post 80km samples. The study revealed that many of the amino acids were lowered in plasma post-exercise but the clearest impact of endurance exercise observed was on fatty acid metabolism with respect to formation of medium chain unsaturated and partially oxidised fatty acids and conjugates of fatty acids with carnitines, which suggested that exercise may have led to increased peroxisomal metabolism. It is becoming increasingly clear that human health is strongly impacted by the gut microbiome. Evaluation of metabolomics effects of E. coli incubation in vivo with different carbon sources of 1% cooked meat, 1% maize meal and 1% olive kernel oil revealed that there were significant effects on amino acid, lipid, carbohydrate, and nucleotide metabolism. In addition, there were effects on intermediates of peptide and polyketide biosynthesis, as well as on xenobiotic breakdown products and vitamin cofactors. These findings suggested that the E. coli metabolome is closely associated with the type of fibre that the microorganism is exposed to and this was consistent with a number of other previous studies.;The study of metabolomic effects of dietary fibres on urinary metabolites from patients with Crohn's disease revealed that each of the 7 dietary fibres did not induce any significant differences in Crohn's disease patients relative to the controls. On the other hand, it was found that metabolites were affected by the time of sample collection post treatment, and the overall effect was that the levels of specific metabolites tended to increase post treatment. The most common pathways affected were those of amino acid metabolism, lipid metabolism, nucleotide metabolism, polyketides, vitamins and cofactors, and xenobiotics, but the effect on carbohydrate metabolism was minimal. Finally, the study to ascertain whether it was possible to predict cancer associated muscle wasting from plasma metabolites in patients with upper gastrointestinal cancer (oesophageal, gastric, pancreatic) revealed that the levels of significantly altered metabolites were generally higher in patients who had lost so much weight (>7.6 kgweight loss). The discriminating metabolites belonged mainly to the lipid metabolic pathways where long chain fatty acids and lysolipids were affected. The observed effects on lipid metabolisms in cancer cachexia suggests that there is an increased tendency towards peroxisomal proliferation in patients who had lost significant muscle mass. Based on these findings, it can be concluded that LC-MS based metabolomics is a valuable tool in discriminating various disease states from the normal physiological state. Although the studies presented in this thesis considered vastly differing physical states ranging from healthy participants performing a simulated ultramarathon exercise on a treadmill to diseased participants suffering from either Crohn's disease or gastrointestinal cancer, the technique was capable of determining the metabolic alterations associated with each disease state. This further reinforces the capacity for metabolomics in discovering new biomarkers for various diseases that could be crucial in the diagnosis, monitoring disease progression, therapeutic efficacy evaluation of novel treatment, and detecting relapses following treatment.Metabolomics remains one of the rapidly growing tools for the identification of new disease diagnostic biomarkers. Mass spectrometry (MS) coupled to a liquid chromatographic (LC) system and nuclear magnetic resonance (NMR) are the two major analytical plaforms currently employed in metabolomic profiling studies of complex biofluid samples. However, due to its inherent higher sensitivity and fast data acquisition, MS remains one of the most dominant analytical techniques used in metabolomics. In this project, metabolomics was employed in various studies to assess metabolite biomarkers associated with health and disease. All the studies employed liquid chromatography-mass spectrometry (LC-MS) on an Orbitrap Exactive mass analyser, andusing ZIC-pHILIC or/and C18 analytical columns. Data was acquired using XCalibur software and metabolite identification was ascertained based on accurate mass detection, retention time comparisons with authentic external standards, and database searching. The acquired data was analysed using both unsupervised (PCA-X) and supervised (OPLS-DA) models in SIMCA in order to determine discriminating metabolite biomarkers responsible for the observed clustering patterns. Investigation of metabolomic effects of an 80 km ultramarathon exercise among healthy volunteers on a treadmill gave clear separation between the pre- and post 80km samples. The study revealed that many of the amino acids were lowered in plasma post-exercise but the clearest impact of endurance exercise observed was on fatty acid metabolism with respect to formation of medium chain unsaturated and partially oxidised fatty acids and conjugates of fatty acids with carnitines, which suggested that exercise may have led to increased peroxisomal metabolism. It is becoming increasingly clear that human health is strongly impacted by the gut microbiome. Evaluation of metabolomics effects of E. coli incubation in vivo with different carbon sources of 1% cooked meat, 1% maize meal and 1% olive kernel oil revealed that there were significant effects on amino acid, lipid, carbohydrate, and nucleotide metabolism. In addition, there were effects on intermediates of peptide and polyketide biosynthesis, as well as on xenobiotic breakdown products and vitamin cofactors. These findings suggested that the E. coli metabolome is closely associated with the type of fibre that the microorganism is exposed to and this was consistent with a number of other previous studies.;The study of metabolomic effects of dietary fibres on urinary metabolites from patients with Crohn's disease revealed that each of the 7 dietary fibres did not induce any significant differences in Crohn's disease patients relative to the controls. On the other hand, it was found that metabolites were affected by the time of sample collection post treatment, and the overall effect was that the levels of specific metabolites tended to increase post treatment. The most common pathways affected were those of amino acid metabolism, lipid metabolism, nucleotide metabolism, polyketides, vitamins and cofactors, and xenobiotics, but the effect on carbohydrate metabolism was minimal. Finally, the study to ascertain whether it was possible to predict cancer associated muscle wasting from plasma metabolites in patients with upper gastrointestinal cancer (oesophageal, gastric, pancreatic) revealed that the levels of significantly altered metabolites were generally higher in patients who had lost so much weight (>7.6 kgweight loss). The discriminating metabolites belonged mainly to the lipid metabolic pathways where long chain fatty acids and lysolipids were affected. The observed effects on lipid metabolisms in cancer cachexia suggests that there is an increased tendency towards peroxisomal proliferation in patients who had lost significant muscle mass. Based on these findings, it can be concluded that LC-MS based metabolomics is a valuable tool in discriminating various disease states from the normal physiological state. Although the studies presented in this thesis considered vastly differing physical states ranging from healthy participants performing a simulated ultramarathon exercise on a treadmill to diseased participants suffering from either Crohn's disease or gastrointestinal cancer, the technique was capable of determining the metabolic alterations associated with each disease state. This further reinforces the capacity for metabolomics in discovering new biomarkers for various diseases that could be crucial in the diagnosis, monitoring disease progression, therapeutic efficacy evaluation of novel treatment, and detecting relapses following treatment
Wind farm control and modelling to provide grid primary response and meet O&M requirements
In the past years, investing in wind industry has been of a great interest. In all future energy scenarios regarding GB power generation, a substantial penetration of wind energy is envisaged. However, at present, except for occasional curtailment of generation, wind farms simply output all the power that can be extracted from the wind at any given time. By increasing the proportion of energy production from wind farms, and especially offshore wind farms, it is of great importance not to operate wind farms in such a simple manner. There is a need of allowing wind farms to operate in a far more flexible way. Regarding the viewpoint of the grid operators, wind farms will need to provide services such as frequency support to match supply and demand. From the viewpoint of the wind farm operators, wind farms will need to be operated in such a manner as to maximise the return of investment. To meet these grid and operator requirements a wind farm controller is developed. The main goal of this thesis is to create a complete power system model to explore whether a wind farm level controller can be utilised to provide ancillary services to the transmission system operator, whilst safe-guarding the wind farm assets. Results from each chapter are novel and provide some new insight towards reducing O&M costs for wind farm operators, while providing advanced flexibility and frequency stability services to the transmission system operator. The thesis concludes that the wind farm controller would be essential for increasing controllability and flexibility of wind farms and improve power system frequency stability.In the past years, investing in wind industry has been of a great interest. In all future energy scenarios regarding GB power generation, a substantial penetration of wind energy is envisaged. However, at present, except for occasional curtailment of generation, wind farms simply output all the power that can be extracted from the wind at any given time. By increasing the proportion of energy production from wind farms, and especially offshore wind farms, it is of great importance not to operate wind farms in such a simple manner. There is a need of allowing wind farms to operate in a far more flexible way. Regarding the viewpoint of the grid operators, wind farms will need to provide services such as frequency support to match supply and demand. From the viewpoint of the wind farm operators, wind farms will need to be operated in such a manner as to maximise the return of investment. To meet these grid and operator requirements a wind farm controller is developed. The main goal of this thesis is to create a complete power system model to explore whether a wind farm level controller can be utilised to provide ancillary services to the transmission system operator, whilst safe-guarding the wind farm assets. Results from each chapter are novel and provide some new insight towards reducing O&M costs for wind farm operators, while providing advanced flexibility and frequency stability services to the transmission system operator. The thesis concludes that the wind farm controller would be essential for increasing controllability and flexibility of wind farms and improve power system frequency stability
Oligonucleotide biosensing applications of distributed feedback lasers and silver nanoparticles, using lasers & silver to find broken hearts
Point of Care devices have helped extend the reach of medical services and improved turnaround times for many traditional laboratory tests. Their development necessitates the development and miniaturisation of novel sensing schemes for rapid monitoring of nanoscale biochemical interactions. Many pathologies such as cardiovascular disease present physical biomarkers in patient samples. By probing at the surface of a thin-film, organic semiconductor, distributed feedback laser a novel biosensing scheme utilizing oligonucleotides has been studied and is reported in this thesis. Using an optical approach, Truxene and BBEHP-PPV DFB lasers are put to the test, assessing their sensing capabilities using laser wavelength shift as the transducing method. Bulk sensitivities of 23 nm.RIU-1 (Tr) and 21 nm.RIU-1 (BBEHP_PPV) are observed. The Tr-DFB lasers demonstrated higher sensitivity in bulk superstrate and surface material adsorption tests.As an alternative to wavelength shift, silver nanoparticle labelled oligonucleotide targets were used to influence the threshold fluence required for OS-DFB lasers to achieve laser action. Using this method, a successful immobilisation strategy for oligonucleotide probes on the surface of an OS-DFB laser, for the first time to our knowledge, was confirmed. Target AgNPs were detected by SERS with a 20x objective on a Raman microscope (Gloucestershire, UK) equipped with an excitation wavelength of 514.5 nm and comparative concentration dependant effects on OS-DFB laser threshold fluence down to 11.5 pM. The capture of 40-45 nm AgNP surface bound target oligonucleotides via hydrogen base pair bonding to corresponding probes on the OS-DFB laser surface was shown to be selective down to individual nucleotide. Such detection limits are within diagnostic significance and the protocols have scope for modification to suit a multitude of different applications.The novel demonstration of a molecular attachment strategy for oligonucleotide biosensor probes to an OS-DFB laser surface and the detection of AgNPs bound by complementary strand hybridisation using SERS and a comparative threshold fluence detection method are of particular note. The text within explores the characteristics of these sensing regimes and compares and contrasts the biosensing technologies involved.Point of Care devices have helped extend the reach of medical services and improved turnaround times for many traditional laboratory tests. Their development necessitates the development and miniaturisation of novel sensing schemes for rapid monitoring of nanoscale biochemical interactions. Many pathologies such as cardiovascular disease present physical biomarkers in patient samples. By probing at the surface of a thin-film, organic semiconductor, distributed feedback laser a novel biosensing scheme utilizing oligonucleotides has been studied and is reported in this thesis. Using an optical approach, Truxene and BBEHP-PPV DFB lasers are put to the test, assessing their sensing capabilities using laser wavelength shift as the transducing method. Bulk sensitivities of 23 nm.RIU-1 (Tr) and 21 nm.RIU-1 (BBEHP_PPV) are observed. The Tr-DFB lasers demonstrated higher sensitivity in bulk superstrate and surface material adsorption tests.As an alternative to wavelength shift, silver nanoparticle labelled oligonucleotide targets were used to influence the threshold fluence required for OS-DFB lasers to achieve laser action. Using this method, a successful immobilisation strategy for oligonucleotide probes on the surface of an OS-DFB laser, for the first time to our knowledge, was confirmed. Target AgNPs were detected by SERS with a 20x objective on a Raman microscope (Gloucestershire, UK) equipped with an excitation wavelength of 514.5 nm and comparative concentration dependant effects on OS-DFB laser threshold fluence down to 11.5 pM. The capture of 40-45 nm AgNP surface bound target oligonucleotides via hydrogen base pair bonding to corresponding probes on the OS-DFB laser surface was shown to be selective down to individual nucleotide. Such detection limits are within diagnostic significance and the protocols have scope for modification to suit a multitude of different applications.The novel demonstration of a molecular attachment strategy for oligonucleotide biosensor probes to an OS-DFB laser surface and the detection of AgNPs bound by complementary strand hybridisation using SERS and a comparative threshold fluence detection method are of particular note. The text within explores the characteristics of these sensing regimes and compares and contrasts the biosensing technologies involved
Development of a decision support tool for day-to-day planning of operations and maintenance logistics for offshore wind farms
The offshore wind industry has grown rapidly in the past decade. Hundreds of turbines are being built in the North Sea every year. Maintenance of offshore assets is often hindered by the weather, vessel limitations and resource shortages. Deciding which maintenance tasks to carry out on the day is challenging, particularly at large wind farms, where operators have hundreds of tasks to choose from. Once the tasks have been selected, the assignment of technicians to vessels and vessels to turbines is decided, usually by human decision makers.In this thesis, methodologies for O&M decision support were developed. Formulation of the problem solved in this thesis was assisted by an offshore wind farm operator to ensure applicability of the developed solutions in the real world. Firstly, a maintenance task prioritisation approach was proposed. Secondly, a tool for optimisation of vessel routes was developed. Given a set of vessels of varying specifications and a set of turbines with a range of maintenance actions to be completed, the tool computes and visualises effective vessel routing policies.The outputs of the task prioritisation model can be used as inputs to the vessel routing optimiser to improve the quality of policies generated by the latter. This was illustrated in two case studies, which provided an in-depth analysis of the outputs of both models. The case studies have shown that considering uncertainties when planning vessel routing can yield up to 14% increase in the number of maintenance actions completed once the uncertainties have realised (compared to a policy which did not take uncertain inputs into account).Additionally, the tool was tested during a visit to an offshore wind farm operations centre. It was shown that given the same choice of maintenance tasks and vessels, the tool exactly matched the policies created by human decision makers.The offshore wind industry has grown rapidly in the past decade. Hundreds of turbines are being built in the North Sea every year. Maintenance of offshore assets is often hindered by the weather, vessel limitations and resource shortages. Deciding which maintenance tasks to carry out on the day is challenging, particularly at large wind farms, where operators have hundreds of tasks to choose from. Once the tasks have been selected, the assignment of technicians to vessels and vessels to turbines is decided, usually by human decision makers.In this thesis, methodologies for O&M decision support were developed. Formulation of the problem solved in this thesis was assisted by an offshore wind farm operator to ensure applicability of the developed solutions in the real world. Firstly, a maintenance task prioritisation approach was proposed. Secondly, a tool for optimisation of vessel routes was developed. Given a set of vessels of varying specifications and a set of turbines with a range of maintenance actions to be completed, the tool computes and visualises effective vessel routing policies.The outputs of the task prioritisation model can be used as inputs to the vessel routing optimiser to improve the quality of policies generated by the latter. This was illustrated in two case studies, which provided an in-depth analysis of the outputs of both models. The case studies have shown that considering uncertainties when planning vessel routing can yield up to 14% increase in the number of maintenance actions completed once the uncertainties have realised (compared to a policy which did not take uncertain inputs into account).Additionally, the tool was tested during a visit to an offshore wind farm operations centre. It was shown that given the same choice of maintenance tasks and vessels, the tool exactly matched the policies created by human decision makers
Structural determination of highly flexible oxylipin natural products via computationally-guided synthesis
A programme of work to further our research towards the total synthesis of (-)-mucosin, a highly flexible oxylipin, has been carried out. This resulted in the investigation of multiple synthetic strategies to afford the desired natural product. These strategies all involved the use of the Kerr group's magnesium bisamide-mediated asymmetric deprotonation methodology as an efficient transformation to introduce asymmetry in our synthesis, and to facilitate the synthesis towards (-)-mucosin. Additionally, the group's magnesium carbon-centered base technology was employed in this work, to aid in delivering the natural product.Following publications from independent researchers, there was strongly compelling evidence suggesting (-)-mucosin had been incorrectly assigned. Considering this, computational chemistry was employed to allow us to propose a probable structure for (-)-mucosin by comparing calculated NMR spectral data with the experimental data available in the chemical literature. Multiple quantitative approaches towards assigning probabilities to possible candidate structure were assessed.A programme of work to further our research towards the total synthesis of (-)-mucosin, a highly flexible oxylipin, has been carried out. This resulted in the investigation of multiple synthetic strategies to afford the desired natural product. These strategies all involved the use of the Kerr group's magnesium bisamide-mediated asymmetric deprotonation methodology as an efficient transformation to introduce asymmetry in our synthesis, and to facilitate the synthesis towards (-)-mucosin. Additionally, the group's magnesium carbon-centered base technology was employed in this work, to aid in delivering the natural product.Following publications from independent researchers, there was strongly compelling evidence suggesting (-)-mucosin had been incorrectly assigned. Considering this, computational chemistry was employed to allow us to propose a probable structure for (-)-mucosin by comparing calculated NMR spectral data with the experimental data available in the chemical literature. Multiple quantitative approaches towards assigning probabilities to possible candidate structure were assessed