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Delivering ancestral tourism in an urban, heritage organisation
Get PDFPreviously held under moratorium from 29th July 2020 until 29th July 2023.Personal heritage tourism is of growing interest in the heritage tourism sector and focuses on an individual’s personal and emotional connections to the heritage sites they visit. Ancestral Tourism is a subset of personal heritage tourism, worthy of investigation as a growth market in many countries, including Scotland. Consumed mainly by the Scottish diaspora in the rest of the UK as well as overseas markets such as the USA, Canada, and Australia, these tourists look upon Scotland as their ancestral homeland and a place to discover their heritage. However, marketing activities and research have focused mainly on rural, Highland regions of the country with provider experiences chiefly explored from the perspective of small, often community-run heritage centres. This study addresses the call for more empirical research on personal heritage tourism, particularly from supplier perspectives, and investigates ancestral tourism provision within a large multifaceted heritage organisation, Glasgow Life. This urban setting embeds the research in a context largely ignored from established ancestral narratives and provision in Scotland. As the official custodian of Glasgow’s heritage resources, Glasgow Life is keen to explore and maximise the potential of ancestral tourism across its museums and archives. The research therefore aims to analyse provision within this publically funded urban heritage context, exploring staff experiences of delivering ancestral tourism, developing an understanding of its potential, and identifying the challenges of coordinating activities across spatially dispersed services. The study is approached from a subjectivist stance, and influenced by hermeneutics, whereby knowledge develops through an iterative process of interaction, analysis, and interpretation. A range of ethnographic techniques was used, including mobile methods, to build an understanding of this complex organisation. This thesis contributes to the under-explored provider perspectives of personal heritage tourism by revealing how staff facilitate and coordinate personal heritage experiences. The findings centre on the diverse ancestral tourists’ needs that an urban setting can meet but also the challenges associated with delivering and coordinating bespoke services in sites which attract many thousands of visitors. It also contributes to literature exploring management challenges in diverse heritage contexts and the tensions surrounding the commercialisation of public heritage. Furthermore, the thesis contributes by extending the conceptualisation of ancestral tourism within an urban context, demonstrating the potential to develop and market ancestral tourism in museums and in urban industrial areas of Scotland.Personal heritage tourism is of growing interest in the heritage tourism sector and focuses on an individual’s personal and emotional connections to the heritage sites they visit. Ancestral Tourism is a subset of personal heritage tourism, worthy of investigation as a growth market in many countries, including Scotland. Consumed mainly by the Scottish diaspora in the rest of the UK as well as overseas markets such as the USA, Canada, and Australia, these tourists look upon Scotland as their ancestral homeland and a place to discover their heritage. However, marketing activities and research have focused mainly on rural, Highland regions of the country with provider experiences chiefly explored from the perspective of small, often community-run heritage centres. This study addresses the call for more empirical research on personal heritage tourism, particularly from supplier perspectives, and investigates ancestral tourism provision within a large multifaceted heritage organisation, Glasgow Life. This urban setting embeds the research in a context largely ignored from established ancestral narratives and provision in Scotland. As the official custodian of Glasgow’s heritage resources, Glasgow Life is keen to explore and maximise the potential of ancestral tourism across its museums and archives. The research therefore aims to analyse provision within this publically funded urban heritage context, exploring staff experiences of delivering ancestral tourism, developing an understanding of its potential, and identifying the challenges of coordinating activities across spatially dispersed services. The study is approached from a subjectivist stance, and influenced by hermeneutics, whereby knowledge develops through an iterative process of interaction, analysis, and interpretation. A range of ethnographic techniques was used, including mobile methods, to build an understanding of this complex organisation. This thesis contributes to the under-explored provider perspectives of personal heritage tourism by revealing how staff facilitate and coordinate personal heritage experiences. The findings centre on the diverse ancestral tourists’ needs that an urban setting can meet but also the challenges associated with delivering and coordinating bespoke services in sites which attract many thousands of visitors. It also contributes to literature exploring management challenges in diverse heritage contexts and the tensions surrounding the commercialisation of public heritage. Furthermore, the thesis contributes by extending the conceptualisation of ancestral tourism within an urban context, demonstrating the potential to develop and market ancestral tourism in museums and in urban industrial areas of Scotland
Modulation of developmental and social behaviour of Pseudomonas spp. in response to phytohormones
No full textThe aim of this thesis was to investigate the effect of phytohormone supplementation on Pseudomonas spp. cultures and identify the hypothetical promotion of biocontrolling properties and reduction of phytopathogenic properties of select species of Pseudomonas. Representative species of Pseudomonas included: P. aeruginosa, P. putida and P. syringae, which were analysed for changes in lifestyle and development, including: colony motility, biofilm formation, dispersal, and several secreted factor analyses. The results show the wide effect of phytohormone supplementation and the division of effect by the phytohormone assayed (between salicylic acid and auxin) and the individual species’ response. Trending stimulation of motility at low concentrations and reduction of biofilm formation and subsequent dispersal was present in majority of strains, however. Insight from investigation allows for further postulation on the usage of phytohormone supplementation to modulate Pseudomonad populations.The aim of this thesis was to investigate the effect of phytohormone supplementation on Pseudomonas spp. cultures and identify the hypothetical promotion of biocontrolling properties and reduction of phytopathogenic properties of select species of Pseudomonas. Representative species of Pseudomonas included: P. aeruginosa, P. putida and P. syringae, which were analysed for changes in lifestyle and development, including: colony motility, biofilm formation, dispersal, and several secreted factor analyses. The results show the wide effect of phytohormone supplementation and the division of effect by the phytohormone assayed (between salicylic acid and auxin) and the individual species’ response. Trending stimulation of motility at low concentrations and reduction of biofilm formation and subsequent dispersal was present in majority of strains, however. Insight from investigation allows for further postulation on the usage of phytohormone supplementation to modulate Pseudomonad populations
Developing spectroscopic serum diagnostics towards clinical translation : the detection and stratification of brain tumours
No full textThis thesis was previously held under moratorium from 28th October 2020 until 28th October 2025.The diagnostic pathway for brain tumour patients is currently ineffective. As there are no methods in place for the early detection of brain cancer, the affected patients’ average life expectancy is reduced by 20 years, which is the highest of all cancer types. Thus, the development of rapid, low-cost platforms in primary care to triage patients for medical imaging may reduce diagnostic delay, whilst potentially providing cost-effective infrastructures for health care providers. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy has demonstrated the ability to diagnose a wide range of pathologies with high accuracies, but the technique is yet to make it into a clinical setting as a regulated spectroscopic test. Recently, innovative high-throughput accessories have been developed which could accelerate clinical translation. The research described in this thesis focuses on the development of the technique by examining the diagnostic ability for the detection and stratification of brain tumours. Initially, the novel high-throughput ATR-FTIR technology was validated in one of the largest spectroscopic studies to date, by separating brain cancer and non-cancer patients with balanced accuracies of 90%, which is comparable to traditional fixed diamond crystal methodology. Distinguishing brain tumour types with serum spectroscopy would be useful for neurologists, as some are difficult to discriminate through medical imaging alone. For example, the highly aggressive glioblastoma and primary cerebral lymphoma (PCNSL) can appear similar on magnetic resonance imaging scans. The differentiation between glioblastoma and PCNSL patients achieved a sensitivity and specificity of 90.1% and 86.3%, respectively. Several other types of brain lesions were then distinguished with balanced accuracies >80%. A reliable blood serum test capable of stratifying brain tumours may avoid the need for surgery in some cases, and could speed up time to definitive treatment. Rapid determination of a glioma patient’s IDH1 status facilitates vital neurosurgical decisions, such as pursuing with resection or opting for alternative therapeutics. Synchrotron-based infrared light has been utilised to probe brain tumour tissue microarrays and differentiate between IDH1-mutated and IDH1-wildtype glioma, at a sensitivity and specificity of 82.4% and 83.4%, respectively. Additionally, centrifugal filtration of patient serum was examined, with the aim of detecting the global epigenetic and metabolic changes associated with mutations in the IDH1 enzyme. The filtration step ultimately improved the classification performance, by delivering a balanced accuracy of 69.1%. Finally, a health economic evaluation was carried out to examine the associated costs and benefits of the blood serum test in clinical practice. Based on recent prospective clinical data, it was found that test costs up to ￡100 would likely be considered cost-effective, whilst primary care tests set at ￡75 would be cost saving to the health services. When comparing the additional costs required for implementing a brain tumour subtype test, the cost-consequence analysis reported an estimated saving of ~￡138,075 per 10,000 patients, equating to a potential saving of ~￡568 per individual cancer case. Furthermore, this could prevent up to 8 unnecessary surgeries, per 100 patients. Therefore, a brain cancer diagnostic test that can also stratify tumour type would have a profound impact for patients, as well as the health services.The diagnostic pathway for brain tumour patients is currently ineffective. As there are no methods in place for the early detection of brain cancer, the affected patients’ average life expectancy is reduced by 20 years, which is the highest of all cancer types. Thus, the development of rapid, low-cost platforms in primary care to triage patients for medical imaging may reduce diagnostic delay, whilst potentially providing cost-effective infrastructures for health care providers. Attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy has demonstrated the ability to diagnose a wide range of pathologies with high accuracies, but the technique is yet to make it into a clinical setting as a regulated spectroscopic test. Recently, innovative high-throughput accessories have been developed which could accelerate clinical translation. The research described in this thesis focuses on the development of the technique by examining the diagnostic ability for the detection and stratification of brain tumours. Initially, the novel high-throughput ATR-FTIR technology was validated in one of the largest spectroscopic studies to date, by separating brain cancer and non-cancer patients with balanced accuracies of 90%, which is comparable to traditional fixed diamond crystal methodology. Distinguishing brain tumour types with serum spectroscopy would be useful for neurologists, as some are difficult to discriminate through medical imaging alone. For example, the highly aggressive glioblastoma and primary cerebral lymphoma (PCNSL) can appear similar on magnetic resonance imaging scans. The differentiation between glioblastoma and PCNSL patients achieved a sensitivity and specificity of 90.1% and 86.3%, respectively. Several other types of brain lesions were then distinguished with balanced accuracies >80%. A reliable blood serum test capable of stratifying brain tumours may avoid the need for surgery in some cases, and could speed up time to definitive treatment. Rapid determination of a glioma patient’s IDH1 status facilitates vital neurosurgical decisions, such as pursuing with resection or opting for alternative therapeutics. Synchrotron-based infrared light has been utilised to probe brain tumour tissue microarrays and differentiate between IDH1-mutated and IDH1-wildtype glioma, at a sensitivity and specificity of 82.4% and 83.4%, respectively. Additionally, centrifugal filtration of patient serum was examined, with the aim of detecting the global epigenetic and metabolic changes associated with mutations in the IDH1 enzyme. The filtration step ultimately improved the classification performance, by delivering a balanced accuracy of 69.1%. Finally, a health economic evaluation was carried out to examine the associated costs and benefits of the blood serum test in clinical practice. Based on recent prospective clinical data, it was found that test costs up to ￡100 would likely be considered cost-effective, whilst primary care tests set at ￡75 would be cost saving to the health services. When comparing the additional costs required for implementing a brain tumour subtype test, the cost-consequence analysis reported an estimated saving of ~￡138,075 per 10,000 patients, equating to a potential saving of ~￡568 per individual cancer case. Furthermore, this could prevent up to 8 unnecessary surgeries, per 100 patients. Therefore, a brain cancer diagnostic test that can also stratify tumour type would have a profound impact for patients, as well as the health services
Next generation optical communications for satellites
No full textThis thesis was previously held under moratorium from 12/11/2020 to 15/11/2022The amount of data being generated and communicated in space is ever increasing. With radio frequency systems becoming increasingly strained under technological and regulatory problems, laser communications has been identified as a key technology in leading a paradigm shift within satellite communications. When compared to traditional radio satellite communications, laser communication techniques show greater performance in terms of available data rates, but also improvements in areas such as a reduction in the size, weight and power of the communication subsystem.Historically, laser communications has been demonstrated on large satellites but their current use upon small satellites (≤ 10 kg) is limited. Within this thesis we address this problem by providing a trade-off analysis for a laser transmitter within space and assess the unique environment in which these laser systems will operate.3 new classes of optical component not previously assessed for space use are tested. A polarisation maintaining hybrid and non-polarisation maintaining hybrid component are shown to suitable for use within a low-Earth orbit environment whilst a compact 1 µm isolator needs to be assessed further. Additionally, a selection of double-clad ErYb-doped fibers are tested to select the most suitable fiber for use within future high-power applications.With a new set of parts tested, the thesis turns towards novel module development. The first module presented is a technology readiness level 5/6 design for a 0.2 W, 1 Gbps laser transmitter designed for CubeSat applications. The optical design is modelled and verified over a temperature range of -5 °C to +50 °C. Finally a multi-channel optical amplifier used for photonic-based radio frequency beam-forming is presented. This amplifier utilises a novel photonic-crystal fiber which was then integrated into a module and performance verified.Having demonstrated the potential for laser communications in small satellite applications. This thesis has helped to provide a technological base on which the nextgeneration of compact, optical communication payloads can be built.The amount of data being generated and communicated in space is ever increasing. With radio frequency systems becoming increasingly strained under technological and regulatory problems, laser communications has been identified as a key technology in leading a paradigm shift within satellite communications. When compared to traditional radio satellite communications, laser communication techniques show greater performance in terms of available data rates, but also improvements in areas such as a reduction in the size, weight and power of the communication subsystem.Historically, laser communications has been demonstrated on large satellites but their current use upon small satellites (≤ 10 kg) is limited. Within this thesis we address this problem by providing a trade-off analysis for a laser transmitter within space and assess the unique environment in which these laser systems will operate.3 new classes of optical component not previously assessed for space use are tested. A polarisation maintaining hybrid and non-polarisation maintaining hybrid component are shown to suitable for use within a low-Earth orbit environment whilst a compact 1 µm isolator needs to be assessed further. Additionally, a selection of double-clad ErYb-doped fibers are tested to select the most suitable fiber for use within future high-power applications.With a new set of parts tested, the thesis turns towards novel module development. The first module presented is a technology readiness level 5/6 design for a 0.2 W, 1 Gbps laser transmitter designed for CubeSat applications. The optical design is modelled and verified over a temperature range of -5 °C to +50 °C. Finally a multi-channel optical amplifier used for photonic-based radio frequency beam-forming is presented. This amplifier utilises a novel photonic-crystal fiber which was then integrated into a module and performance verified.Having demonstrated the potential for laser communications in small satellite applications. This thesis has helped to provide a technological base on which the nextgeneration of compact, optical communication payloads can be built
Studies of biofluid analysis using 2D-IR spectroscopy
Get PDFIn this thesis, the application of two-dimensional infrared (2D-IR) spectroscopy is evaluated to provide a quantitative analysis of the protein content of blood serum. The foremost challenge is obtaining protein measurements in physiologically relevant solvents as the most informative infrared peak relating to protein studies, the amide I band, overlaps with the bending mode of H2O, making label-free detection of the protein content in serum challenging. This project demonstrates that 2D-IR can surmount the major obstacle to serum protein analysis as the 2D-IR amide I signature of proteins is shown to dominate that of water. Furthermore the link between protein secondary structure and the 2D-IR amide I lineshape allows differentiation of protein signals in serum leading to clinically relevant measurements of the biomedically important proteins. Detection limits for 2D-IR are also established allowing projection of the sensitivity of 2D-IR for future applications. Quantification of proteins is key for diagnosis and prognosis outcomes, however using 2D-IR, standardisation of measurement protocols needs to be addressed in order to achieve this.;A new method is demonstrated for 2D-IR spectroscopy to internally normalise spectral signals, allowing normalisation of the protein response to the thermal response of water which is temporally separate from the protein signal, reducing the impact of measurement fluctuations on the data. Furthermore, normalisation of sample signals enables calibration curves of serum albumin to be produced allowing absolute protein concentrations to be obtained using 2D-IR spectroscopy. The application of 2D-IR is explored further and attempts to detect drug-binding at clinically relevant levels to serum albumin are made. Changes in the secondary structure of albuminare detected upon drug-binding however the complex nature of serum makes assigning changes observed using 2D-IR challenging.In this thesis, the application of two-dimensional infrared (2D-IR) spectroscopy is evaluated to provide a quantitative analysis of the protein content of blood serum. The foremost challenge is obtaining protein measurements in physiologically relevant solvents as the most informative infrared peak relating to protein studies, the amide I band, overlaps with the bending mode of H2O, making label-free detection of the protein content in serum challenging. This project demonstrates that 2D-IR can surmount the major obstacle to serum protein analysis as the 2D-IR amide I signature of proteins is shown to dominate that of water. Furthermore the link between protein secondary structure and the 2D-IR amide I lineshape allows differentiation of protein signals in serum leading to clinically relevant measurements of the biomedically important proteins. Detection limits for 2D-IR are also established allowing projection of the sensitivity of 2D-IR for future applications. Quantification of proteins is key for diagnosis and prognosis outcomes, however using 2D-IR, standardisation of measurement protocols needs to be addressed in order to achieve this.;A new method is demonstrated for 2D-IR spectroscopy to internally normalise spectral signals, allowing normalisation of the protein response to the thermal response of water which is temporally separate from the protein signal, reducing the impact of measurement fluctuations on the data. Furthermore, normalisation of sample signals enables calibration curves of serum albumin to be produced allowing absolute protein concentrations to be obtained using 2D-IR spectroscopy. The application of 2D-IR is explored further and attempts to detect drug-binding at clinically relevant levels to serum albumin are made. Changes in the secondary structure of albuminare detected upon drug-binding however the complex nature of serum makes assigning changes observed using 2D-IR challenging
Regulation and roles of nutrient-dependent mitochondrial fusion
Get PDFMitochondria continuously alter their shape via fusion and fission and interestingly, this dynamic balance is critical for maintaining organelle function and cellular homeostasis. Studies have shown that mitochondria undergo fusion during amino acid starvation-induced autophagy. This mitochondrial response has been proposed to be regulated by MTORC1, a key regulator of nutrient-sensing signalling pathway. However, the mechanism linking MTORC1 and nutrient sensing to mitochondrial hyperfusion has not been fully elucidated.;This project aimed at studying mitochondrial remodelling during nutrient starvation. As a sensor of regulatory amino acids, the role of MTORC1 in the regulation of mitochondrial fusion was studied. In addition, this study also aimed to investigate the kinase-dependent regulation of mitochondrial fusion during amino acid starvation. This project studied the roles of the Ulk1, AMPK and PKA pathways in amino acid starvation-dependent mitochondrial fusion. Using a metabolomics approach, this project also studied changes in cellular metabolism during amino acid starvation-dependent mitochondrial fusion and how hyperfusion could crosstalk with these metabolic changes.;The results in this study indicated that mitochondria undergo remodelling towards a hyperfused state specifically in response to amino acid availability. Importantly, mitochondria surprisingly undergo extensive hyperfusion in response to elevated levels of glutamine (Q), leucine (L) and arginine (R). Contrary to predictions from the current model, mitochondria sensed Q, L and R levels independently of MTORC1. Interestingly, amino acid-dependent mitochondrial hyperfusion critically required the Ulk1/2 autophagy initiation complex. In addition, amino acid-dependent mitochondrial hyperfusion did not require AMPK and PKA-dependent phosphorylation of Drp1. However, amino acid-dependent mitochondrial fusion required the regulators, Optic atrophy 1 (Opa1) and Mitofusin 1 (Mfn1).;Metabolomic analysis revealed both QLR-dependent and fusion-dependent changes in levels of metabolites involved in the urea cycle, Krebs cycle and REDOX balance. Findings in this project suggest putative mechanisms linking amino acid metabolism, mitochondrial dynamics and mitochondrial function.Mitochondria continuously alter their shape via fusion and fission and interestingly, this dynamic balance is critical for maintaining organelle function and cellular homeostasis. Studies have shown that mitochondria undergo fusion during amino acid starvation-induced autophagy. This mitochondrial response has been proposed to be regulated by MTORC1, a key regulator of nutrient-sensing signalling pathway. However, the mechanism linking MTORC1 and nutrient sensing to mitochondrial hyperfusion has not been fully elucidated.;This project aimed at studying mitochondrial remodelling during nutrient starvation. As a sensor of regulatory amino acids, the role of MTORC1 in the regulation of mitochondrial fusion was studied. In addition, this study also aimed to investigate the kinase-dependent regulation of mitochondrial fusion during amino acid starvation. This project studied the roles of the Ulk1, AMPK and PKA pathways in amino acid starvation-dependent mitochondrial fusion. Using a metabolomics approach, this project also studied changes in cellular metabolism during amino acid starvation-dependent mitochondrial fusion and how hyperfusion could crosstalk with these metabolic changes.;The results in this study indicated that mitochondria undergo remodelling towards a hyperfused state specifically in response to amino acid availability. Importantly, mitochondria surprisingly undergo extensive hyperfusion in response to elevated levels of glutamine (Q), leucine (L) and arginine (R). Contrary to predictions from the current model, mitochondria sensed Q, L and R levels independently of MTORC1. Interestingly, amino acid-dependent mitochondrial hyperfusion critically required the Ulk1/2 autophagy initiation complex. In addition, amino acid-dependent mitochondrial hyperfusion did not require AMPK and PKA-dependent phosphorylation of Drp1. However, amino acid-dependent mitochondrial fusion required the regulators, Optic atrophy 1 (Opa1) and Mitofusin 1 (Mfn1).;Metabolomic analysis revealed both QLR-dependent and fusion-dependent changes in levels of metabolites involved in the urea cycle, Krebs cycle and REDOX balance. Findings in this project suggest putative mechanisms linking amino acid metabolism, mitochondrial dynamics and mitochondrial function
Combining a microfluidic platform with LC-MS for the detection of induced hepatotoxicity using primary hepatic spheroids
Get PDFThe success rate of bringing a new drug from conception to market is extremely low as well as time consuming and very costly. Simple sub-cellular models can provide high throughput data allowing early detection of many drugs doomed to fail, but do not encompass the complexity found in whole cell based models, which provide more in-depth data. Cell culture models have evolved from simple 2-dimensional cultures on hard substrates i.e. plastic dishes, to 3 dimensional cultures that promote and enhance in vivo-like function and architecture. The liver is the main organ of interest during the drug development stages, as it is the organ that metabolizes xenobiotics. Drug metabolism entails converting a compound into a more hydrophilic state that can be actively excreted.;However, the process of metabolism does sometimes result in the creation of a toxic intermediate metabolite that can lead to drug-induced liver injury. Thus to increase the efficacy of drug development the models, which are often scare and / or costly, and screening methods employed would need to be optimized. Microfluidics enables miniaturization through the control and manipulation of fluids n the nano - to millilitre range. Combining microfluidics with appropriate 2 dimensional / 3 dimensional cell culture systems can lead to higher throughput data production using far less resources compared to conventional culturing methods; and when combined with a screening modality that allows collection of detailed information it could be used to improve the efficacy of the preclinical drug-development process. One such modality is liquid chromatography-mass spectrometry.;The chromatography technology allows separation of compounds from a mixed sample based on the interactions between the compounds of interest and the mobile and stationary phase. This enables quantitative analysis based on the retention time and absorbance measured by the detector. Mass spectrometry allows identification of the chemical composition of a component based on the mass-to-charge ratio. Both technologies are highly-sensitive and specific, which is ideally suited for metabolic analysis. In this thesis the effects of a miniaturisation process on cell culture environment are investigated, specifically the effect of using far less cells to form functional, metabolically active 3-dimensional liver spheroids, compared with conventional methods. HepG2 and primary rat hepatocyte spheroids were cultured in a microfluidic platform and exposed to drugs known to induce toxicity.;The cells were cultured for 4 days before being exposed to each drug for 24 hours. Half the cultures were analyzed the following day and the other half were allowed to recover for an additional 24 hours. The platforms were compared to a gold standard culture model, a collagen sandwich culture. Cell supernatant and lysate samples were analyzed using liquid chromatography-mass spectrometry. The results showed that similar data could be obtained from the microfluidic platforms compared to collagen sandwich configurations when screening phase I and phase II metabolites, using far less cells and culture media. In conclusion, metabolically active liver spheroids can be generated using far less cell than previously thought. Information about metabolism can be extracted when combining the microfluidic cell culture system with liquid chromatography-mass spectrometry.The success rate of bringing a new drug from conception to market is extremely low as well as time consuming and very costly. Simple sub-cellular models can provide high throughput data allowing early detection of many drugs doomed to fail, but do not encompass the complexity found in whole cell based models, which provide more in-depth data. Cell culture models have evolved from simple 2-dimensional cultures on hard substrates i.e. plastic dishes, to 3 dimensional cultures that promote and enhance in vivo-like function and architecture. The liver is the main organ of interest during the drug development stages, as it is the organ that metabolizes xenobiotics. Drug metabolism entails converting a compound into a more hydrophilic state that can be actively excreted.;However, the process of metabolism does sometimes result in the creation of a toxic intermediate metabolite that can lead to drug-induced liver injury. Thus to increase the efficacy of drug development the models, which are often scare and / or costly, and screening methods employed would need to be optimized. Microfluidics enables miniaturization through the control and manipulation of fluids n the nano - to millilitre range. Combining microfluidics with appropriate 2 dimensional / 3 dimensional cell culture systems can lead to higher throughput data production using far less resources compared to conventional culturing methods; and when combined with a screening modality that allows collection of detailed information it could be used to improve the efficacy of the preclinical drug-development process. One such modality is liquid chromatography-mass spectrometry.;The chromatography technology allows separation of compounds from a mixed sample based on the interactions between the compounds of interest and the mobile and stationary phase. This enables quantitative analysis based on the retention time and absorbance measured by the detector. Mass spectrometry allows identification of the chemical composition of a component based on the mass-to-charge ratio. Both technologies are highly-sensitive and specific, which is ideally suited for metabolic analysis. In this thesis the effects of a miniaturisation process on cell culture environment are investigated, specifically the effect of using far less cells to form functional, metabolically active 3-dimensional liver spheroids, compared with conventional methods. HepG2 and primary rat hepatocyte spheroids were cultured in a microfluidic platform and exposed to drugs known to induce toxicity.;The cells were cultured for 4 days before being exposed to each drug for 24 hours. Half the cultures were analyzed the following day and the other half were allowed to recover for an additional 24 hours. The platforms were compared to a gold standard culture model, a collagen sandwich culture. Cell supernatant and lysate samples were analyzed using liquid chromatography-mass spectrometry. The results showed that similar data could be obtained from the microfluidic platforms compared to collagen sandwich configurations when screening phase I and phase II metabolites, using far less cells and culture media. In conclusion, metabolically active liver spheroids can be generated using far less cell than previously thought. Information about metabolism can be extracted when combining the microfluidic cell culture system with liquid chromatography-mass spectrometry
Reconfiguring the ship environment for damage stability enhancement
Get PDFIt has often been said that, from a fundamental Naval Architecture perspective, the primary design objective to be achieved is for a ship to remain afloat and upright (safety-related objectives). This is particularly true in case of vessel flooding, where this objective becomes harder still. The traditional risk control option adopted in Naval Architecture to meet safety related objectives is by rules and regulations, targeting damage limitation, nominally instigated in the wake of maritime accidents claiming heavy loss of life. The first Merchant Shipping Act of1854 is the earliest known legal requirement addressing safety at sea and concerning watertight bulkheads, i.e., permanent (passive) reconfiguration of the internal ship environment to enhance safety. This has been the most common measure, manifesting itself in the wake of every serious flooding accident since the beginning, back in the 19th century. Notably, with accidents providing the main motivation, emphasis has primarily been placed on reducing consequences, i.e., on cure rather than prevention.;The key reason for this, derives from the fact that the residual risk post flooding accidents is unacceptably high, meaning that the most-cost-effective way to reduce flooding risk is to target the residual risk. This being the case, the prevailing situation can be drastically improved through understanding of the underlying mechanisms leading to vessel loss and to identification of governing design and operational parameters to target flooding risk reduction more cost-effectively. On one hand, this necessitates the development of appropriate methods, tools and techniques capable of meaningfully addressing the physical phenomena involved. On the other hand, this nurtures wider understanding and wisdom. Safety is normally a compromise to vessel earning potential and, as public demand for higher safety standards grows, industry is forced to choose between viability of business and safety of customers. Unfortunately, in any such compromise, safety loses. However, the key reason for this is strongly linked to the traditional myopic focus on only permanent, designed-related safety measures, pertaining in particular to flooding incidents.;Traditional flooding protection through watertight subdivisionis largely dictated by IMO regulations and has a physical limit which, if exceeded, a safety plateau is reached. This is currently the case and with damage stability standards progressively increasing, the safety gap between existing and new ships is dangerously widening. Adding to the problem is the progressive erosion of design stability margins, making stability management unsustainable and leading to loss of earnings at best. The need for monitoring and managing the residual risk through active intervention/protection over the life-cycle of the vessel drives the industry in searching to adopt a new normal. This new normal is the innovation being explored in this thesis, by addressing safety enchantment through a systematic reconfiguration of the ship environment for passive and active protection in flooding (and to some extent fire) accidents. In this respect, the "design-optimal" internal arrangement of a vessel, is adapted and reconfigured, using passive and active containment systems for flooding/fire incidents, in the form of high expansion foam products. Several case studies are being presented to explain and explore the safety-enhancement potential. This demonstrates transformational reduction in flooding/fire risk, in the most cost-effective way available.It has often been said that, from a fundamental Naval Architecture perspective, the primary design objective to be achieved is for a ship to remain afloat and upright (safety-related objectives). This is particularly true in case of vessel flooding, where this objective becomes harder still. The traditional risk control option adopted in Naval Architecture to meet safety related objectives is by rules and regulations, targeting damage limitation, nominally instigated in the wake of maritime accidents claiming heavy loss of life. The first Merchant Shipping Act of1854 is the earliest known legal requirement addressing safety at sea and concerning watertight bulkheads, i.e., permanent (passive) reconfiguration of the internal ship environment to enhance safety. This has been the most common measure, manifesting itself in the wake of every serious flooding accident since the beginning, back in the 19th century. Notably, with accidents providing the main motivation, emphasis has primarily been placed on reducing consequences, i.e., on cure rather than prevention.;The key reason for this, derives from the fact that the residual risk post flooding accidents is unacceptably high, meaning that the most-cost-effective way to reduce flooding risk is to target the residual risk. This being the case, the prevailing situation can be drastically improved through understanding of the underlying mechanisms leading to vessel loss and to identification of governing design and operational parameters to target flooding risk reduction more cost-effectively. On one hand, this necessitates the development of appropriate methods, tools and techniques capable of meaningfully addressing the physical phenomena involved. On the other hand, this nurtures wider understanding and wisdom. Safety is normally a compromise to vessel earning potential and, as public demand for higher safety standards grows, industry is forced to choose between viability of business and safety of customers. Unfortunately, in any such compromise, safety loses. However, the key reason for this is strongly linked to the traditional myopic focus on only permanent, designed-related safety measures, pertaining in particular to flooding incidents.;Traditional flooding protection through watertight subdivisionis largely dictated by IMO regulations and has a physical limit which, if exceeded, a safety plateau is reached. This is currently the case and with damage stability standards progressively increasing, the safety gap between existing and new ships is dangerously widening. Adding to the problem is the progressive erosion of design stability margins, making stability management unsustainable and leading to loss of earnings at best. The need for monitoring and managing the residual risk through active intervention/protection over the life-cycle of the vessel drives the industry in searching to adopt a new normal. This new normal is the innovation being explored in this thesis, by addressing safety enchantment through a systematic reconfiguration of the ship environment for passive and active protection in flooding (and to some extent fire) accidents. In this respect, the "design-optimal" internal arrangement of a vessel, is adapted and reconfigured, using passive and active containment systems for flooding/fire incidents, in the form of high expansion foam products. Several case studies are being presented to explain and explore the safety-enhancement potential. This demonstrates transformational reduction in flooding/fire risk, in the most cost-effective way available
A study of the forming limits of cold and hot forming of aluminium alloy sheets with multi-point tooling
Get PDFThis thesis was previously held under moratorium between December 2020 and January 2023.Multi-point forming (MPF) is a special category of sheet metal forming techniques with good operational flexibilities due to using two sets of adjustable pins along the machine ram direction. These pins represent the acting points of the desired forming-tool surface contours. Although this technology has already been widely used for the shaping of panel components, it has been little tested for the forming of lightweight metal sheets with high strength.Forming of lightweight metallic materials, such as aluminium alloys, has been widely deployed in the Aerospace and Automotive industry. Nevertheless, some challenges still exist when the forming takes place under different process and machine-set conditions, especially materials such as high strength aluminium alloy sheets.Hot stamping technology is capable of improving the material properties and forming limits while reducing the forming-force requirement and springback. This could be enhanced particularly by integrating an intermediate fast cooling process into the process chain of the forming of aluminium alloys. However the spray cooling that is currently popular in industry cannot achieve the required high cooling rates, while introduction of an intermediate fast cooling process into an industry process is hampered by lack of the industrially viable tooling. To address the issues mentioned above, this PhD research studies the feasibility of combining multi-point forming and hot-forming to shape the high-strength Aluminium alloy sheets. This is done with a view to improving the manufacturing flexibility while the capability of forming high-strength sheet-metals is maintained. This new capability was further enhanced by developing a fast contact-cooling facility and integrating it into a pilot prototype production line. The fundamental and process studies combined with the two test cases, deep drawing and stretch forming with multi-point tooling, suggest a feasible alternative route for the forming of lightweight high-strength sheet-metals. The pilot line established shows that the fast contact-cooling technology is effective for application in an industrial metal forming process.With this pilot line, the aluminium sheets heated up by the electricalfurnace were subjected to the intermediate cooling prior to the loading into the multi-point tooling for forming. Different cooling rates, such as 50 °C/s and 100 °C/s, have been tested, and their effects on the forming limits for different component-forms investigated. AA6082 sheet blanks were used as the raw material; several square cups with different depths were formed; and the temperatures of the sheet blanks were monitored during the teststhrough a built-in monitoring system. The tests conducted demonstrated that the integration of fast contact cooling into a production process is feasible and its associated cost couldbe relatively low. It also demonstrated that introducing a high-temperature forming configuration into a multi-point tooling forming process is feasible, which extends the existing process capabilities. The test results showed that proper cooling rates, which are achievable easily with the facility developed, could improve forming limits of the high strength aluminium alloys greatly, although, in general, the higher the cooling rate, the better results are obtained. At the same time, the fast-cooling configuration design could, potentially, lead to significant process-time saving, due to the extremely short cooling time involved.Multi-point forming (MPF) is a special category of sheet metal forming techniques with good operational flexibilities due to using two sets of adjustable pins along the machine ram direction. These pins represent the acting points of the desired forming-tool surface contours. Although this technology has already been widely used for the shaping of panel components, it has been little tested for the forming of lightweight metal sheets with high strength.Forming of lightweight metallic materials, such as aluminium alloys, has been widely deployed in the Aerospace and Automotive industry. Nevertheless, some challenges still exist when the forming takes place under different process and machine-set conditions, especially materials such as high strength aluminium alloy sheets.Hot stamping technology is capable of improving the material properties and forming limits while reducing the forming-force requirement and springback. This could be enhanced particularly by integrating an intermediate fast cooling process into the process chain of the forming of aluminium alloys. However the spray cooling that is currently popular in industry cannot achieve the required high cooling rates, while introduction of an intermediate fast cooling process into an industry process is hampered by lack of the industrially viable tooling. To address the issues mentioned above, this PhD research studies the feasibility of combining multi-point forming and hot-forming to shape the high-strength Aluminium alloy sheets. This is done with a view to improving the manufacturing flexibility while the capability of forming high-strength sheet-metals is maintained. This new capability was further enhanced by developing a fast contact-cooling facility and integrating it into a pilot prototype production line. The fundamental and process studies combined with the two test cases, deep drawing and stretch forming with multi-point tooling, suggest a feasible alternative route for the forming of lightweight high-strength sheet-metals. The pilot line established shows that the fast contact-cooling technology is effective for application in an industrial metal forming process.With this pilot line, the aluminium sheets heated up by the electricalfurnace were subjected to the intermediate cooling prior to the loading into the multi-point tooling for forming. Different cooling rates, such as 50 °C/s and 100 °C/s, have been tested, and their effects on the forming limits for different component-forms investigated. AA6082 sheet blanks were used as the raw material; several square cups with different depths were formed; and the temperatures of the sheet blanks were monitored during the teststhrough a built-in monitoring system. The tests conducted demonstrated that the integration of fast contact cooling into a production process is feasible and its associated cost couldbe relatively low. It also demonstrated that introducing a high-temperature forming configuration into a multi-point tooling forming process is feasible, which extends the existing process capabilities. The test results showed that proper cooling rates, which are achievable easily with the facility developed, could improve forming limits of the high strength aluminium alloys greatly, although, in general, the higher the cooling rate, the better results are obtained. At the same time, the fast-cooling configuration design could, potentially, lead to significant process-time saving, due to the extremely short cooling time involved
Software-in-the-loop applications for improved physical model tests of ocean renewable energy devices using artificial intelligence
Get PDFExperimental research in laboratory is a necessary and useful method to explore the full potential of a device. Because it does not only require much less money than the prototype at sea test, it also provides more reliable results compared to numerical simulations. Hence, it is significantly vital to make accurate model tests of the concerned ocean renewable energy (ORE) devices possible. For this reason, this study for a PhD degree has been finished and a thesis, therefore, is produced. There is a need for a method to provide linear or nonlinear real-time power-take-off forces to the wave energy converting mechanism in the water during the experiment. More urgently, it is essential to overcome the discrepancy caused by following Froude-scaling law and Reynold-scaling law in the test of a model-scaled FOWT. Two applications for WECs and FOWTs are proposed separately, to meet the challenges.;Following the conceptual design of the software-in-the-loop (SIL) application for a WEC, an innovative generic platform, which can explicitly provide a real-time PTO damping force in terms of either linear or non-linear (at different scales) is developed and characterised by 1349 drop tests. Subsequent physical model tests of a OWSC WEC device are carried out. The power efficiency of the OWSC WEC device under different PTO strategies is then estimated based on the analysis of experimental results. The best linear damping in regular waves is driven by gaining 80 in the control function, while 160 for nonlinear PTO damping. Furthermore, it is revealed that nonlinear PTOs have no distinct advantage in the amount of electricity output, but can lead to better stability and broader damping range. Following the conceptual design of an AI-based hybrid testing application for a FOWT system, a prediction module of the rotor thrust is needed to be estimated and optimised in the first place. For this reason, a considerable amount of simulations under various conditions are carried out by fully-coupled computation software, and the results obtained are used to train an artificial intelligence structure. Then a prediction module which depends on five inputs, and gives one output rotor thrust, is estimated mathematically. The mathematical module is converted to the control function in the program in a controller to execute it in real-time tests. Therefore, the AI machine is sometimes referred to as the SIL application for FOWTs, which consists of a prediction module obtained by AI training, a controller, and the program in the controller. The AI machine is the key component to implement the AI-based real-time hybrid model (AIReaTHM) testing methodology.;As one of the highlights in the present study, the AIReaTHM testing rig is developed, and bench tests are carried out with a manoeuvrable motion simulator. The comprehensive testing results are analysed for three purposes: 1, validating the AIReaTHM testing methodology. 2, assessing the influences of wind speed, wind turbulence intensity, wave spectrum, input hydrodynamic motions on rotor thrust are reflected by the SIL application.3, evaluating the systematic uncertainty in the testing rig, which is to be compensated by further improving the testing system. The effect of the surge frequency, wave spectrum and wind models have on the targeted thrust is discussed. The time delay in the testing system is identified as within 0.1s, and the overall uncertainty from the testing rig is 5-15KN (the minimum rotor thrust is 508KN, hence the uncertainty is 0.98%-2.95% in percentage) when compared to the AI prediction.;The testing rig developed is further applied to a 1:73 model of a Hywind floating wind turbine. 4 testing campaigns are carried out, and 303 independent tests are conducted. Testing results with the real-time rotor thrust provided by the AI-based software-in-the-loop application are compared with the other three comparative testing patterns. They are tests with a constant rotor thrust, without any rotor thrust, with AI predicted rotor thrust but without wave inputs, and in only wave conditions respectively. The performance of the rotor thrust obtained by the AI prediction agrees well with the benchmark testing results. Then, the hydrodynamic responses of the model are compared among those four testing patterns, for both regular wave tests and irregular wave tests in terms of time histories, RAOs, statistical analysis, and spectral analysis. The RAOs of the model under three testing patterns are given for regular wave tests. The hydrodynamic response revealed that the AIReaTHM is better than applying a constant rotor thrust atop of the model, though further improvement is required to meet realistic response. In the final chapter, conclusions are drawn and original contribution of this PhD study is outlined. Besides, a few points concerning future work are addressed.Experimental research in laboratory is a necessary and useful method to explore the full potential of a device. Because it does not only require much less money than the prototype at sea test, it also provides more reliable results compared to numerical simulations. Hence, it is significantly vital to make accurate model tests of the concerned ocean renewable energy (ORE) devices possible. For this reason, this study for a PhD degree has been finished and a thesis, therefore, is produced. There is a need for a method to provide linear or nonlinear real-time power-take-off forces to the wave energy converting mechanism in the water during the experiment. More urgently, it is essential to overcome the discrepancy caused by following Froude-scaling law and Reynold-scaling law in the test of a model-scaled FOWT. Two applications for WECs and FOWTs are proposed separately, to meet the challenges.;Following the conceptual design of the software-in-the-loop (SIL) application for a WEC, an innovative generic platform, which can explicitly provide a real-time PTO damping force in terms of either linear or non-linear (at different scales) is developed and characterised by 1349 drop tests. Subsequent physical model tests of a OWSC WEC device are carried out. The power efficiency of the OWSC WEC device under different PTO strategies is then estimated based on the analysis of experimental results. The best linear damping in regular waves is driven by gaining 80 in the control function, while 160 for nonlinear PTO damping. Furthermore, it is revealed that nonlinear PTOs have no distinct advantage in the amount of electricity output, but can lead to better stability and broader damping range. Following the conceptual design of an AI-based hybrid testing application for a FOWT system, a prediction module of the rotor thrust is needed to be estimated and optimised in the first place. For this reason, a considerable amount of simulations under various conditions are carried out by fully-coupled computation software, and the results obtained are used to train an artificial intelligence structure. Then a prediction module which depends on five inputs, and gives one output rotor thrust, is estimated mathematically. The mathematical module is converted to the control function in the program in a controller to execute it in real-time tests. Therefore, the AI machine is sometimes referred to as the SIL application for FOWTs, which consists of a prediction module obtained by AI training, a controller, and the program in the controller. The AI machine is the key component to implement the AI-based real-time hybrid model (AIReaTHM) testing methodology.;As one of the highlights in the present study, the AIReaTHM testing rig is developed, and bench tests are carried out with a manoeuvrable motion simulator. The comprehensive testing results are analysed for three purposes: 1, validating the AIReaTHM testing methodology. 2, assessing the influences of wind speed, wind turbulence intensity, wave spectrum, input hydrodynamic motions on rotor thrust are reflected by the SIL application.3, evaluating the systematic uncertainty in the testing rig, which is to be compensated by further improving the testing system. The effect of the surge frequency, wave spectrum and wind models have on the targeted thrust is discussed. The time delay in the testing system is identified as within 0.1s, and the overall uncertainty from the testing rig is 5-15KN (the minimum rotor thrust is 508KN, hence the uncertainty is 0.98%-2.95% in percentage) when compared to the AI prediction.;The testing rig developed is further applied to a 1:73 model of a Hywind floating wind turbine. 4 testing campaigns are carried out, and 303 independent tests are conducted. Testing results with the real-time rotor thrust provided by the AI-based software-in-the-loop application are compared with the other three comparative testing patterns. They are tests with a constant rotor thrust, without any rotor thrust, with AI predicted rotor thrust but without wave inputs, and in only wave conditions respectively. The performance of the rotor thrust obtained by the AI prediction agrees well with the benchmark testing results. Then, the hydrodynamic responses of the model are compared among those four testing patterns, for both regular wave tests and irregular wave tests in terms of time histories, RAOs, statistical analysis, and spectral analysis. The RAOs of the model under three testing patterns are given for regular wave tests. The hydrodynamic response revealed that the AIReaTHM is better than applying a constant rotor thrust atop of the model, though further improvement is required to meet realistic response. In the final chapter, conclusions are drawn and original contribution of this PhD study is outlined. Besides, a few points concerning future work are addressed
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