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Modeling the potential impacts of climate change on surface and groundwater resources in the Niger Delta part of Nigeria
Get PDFPreviously held under moratorium from 1st July 2021 until 1st July 2024.Climate change impact studies are challenging in developing countries due to the paucity of climatological datasets resulting from insufficient monitoring stations, and constraint in human and computational resources. The Niger Delta region is one of the most vulnerable and densely populated regions in Nigeria, which presents special challenges for water resource policy and management due to climate change and anthropogenic activities, especially with an increase in water demands. Flooding events are recorded annually in settlements along River Niger and its tributaries, inundating many towns, displacing people from their homes and polluting the surface and groundwater resources. As the surface and groundwater resources are two interconnected components of one single resource, any negative impacts on one will inevitably affect the quantity or quality of the other component. The increase in intense stress on the groundwater from shallow coastal plain sand aquifers as the significant source of water resources for domestic, industrial and agricultural purposes in the area. This study, therefore, presents a novel approach for climate change impact assessment on surface and groundwater resources in developing countries.
The first stage of this study assessed the performance of three widely used daily gridded precipitation (prcp), maximum and minimum temperature (Tmax and Tmin) datasets from the Climatic Research Unit (CRU), Princeton University Global Meteorological Forcing (PGF) and Climate Forecast System Reanalysis (CFSR) datasets available over the Niger Delta part of Nigeria against the observed station datasets to select the best datasets that can serve as a possible replacement to the observed datasets. Symmetrical uncertainty (SU) filter was employed together with the selected hydro-climatological datasets to assess the performance of 26 Coupled Model Intercomparison Project Phase 5 (CMIP5) general circulation model (GCM) outputs. The selection was made according to their capability to simulate observed daily precipitation (prcp), maximum and minimum temperature (Tmax and Tmin) over the historical period 1980โ2005 (Baseline periods) in the Niger Delta region. The selected GCMs were used for climate change predictions and impacts assessment over the period 2020s (2010โ2039), 2050s (2040โ2069) and 2080s (2070โ2099), under Representative Concentration Pathway (RCP) 4.5 and 8.5. Standardized precipitation index (SPI) of 1-month and 12-month time steps were used for extreme event assessment. SWAT (Soil and Water Assessment Tool) model was used to analyse the effects of climate change on the hydrologic processes of the Niger River Basin (NRB) in Nigeria. The hydrostratigraphy of the Niger Delta shallow coastal aquifers was characterised coupled with the simulated aquifer recharge and evapotranspiration deduced from Global Climate Model (GCM) simulations under two Representative concentration pathways (RCP4.5 and RCP8.5) to develop a transient groundwater flow model to investigate the potential impacts of climate change and increased groundwater abstraction on the coastal plain sand aquifer over the periods 2010 to 2099.
Results of the hydro-climatological study revealed that the CRU datasets performed better in most of the statistical assessments conducted. The symmetrical uncertainty filter revealed the four top-ranked GCMs, namely ACCESS1.3, MIROCESM, MIROC-ESM-CHM, and NorESM1-M as the best set of GCMs to form an
ensemble for the Spatio-temporal climate projection over the study area. The selected GCM ensemble predicted an increase in the mean annual precipitation in the range of 0.26% to 3.57% under RCP4.5, and 0.7% to 4.94% under RCP 8.5 by the end of the century as compared to the base period. The study also revealed an increase in maximum temperature in the range of 0 to 0.4 ยฐC under RCP4.5 and 1.25โ1.79 ยฐC under RCP8.5 during the periods 2080s. Minimum temperature also revealed a significant increase of 0 to 0.52 ยฐC under RCP4.5 and between 1.38โ2.02 ยฐC under RCP8.5, which indicates that there might be the occurrence of extreme events in the Niger Delta due to climate change. The 1-month and 12-month SPI under both RCPs predict incidences of extreme wet cycle across all the study locations, especially during the 2080s. The mean annual streamflow was also predicted to increase from 21% to 48% at the Onitsha gauging station under both emission scenarios.
Results of hydrostratigraphic studies revealed that the system was more complicated than previously reported. A unit of silty sand was observed in the western part of the basin, which thins out leaving the eastern part of the basin as an unconfined aquifer underlain by multiple thin beds of the sand aquifer and a layered sand aquifer, which holds freshwater occurring in the northern parts of the basin. Transient groundwater flow model simulations of Port-Harcourt metropolis predicted the maximum change in groundwater budget and levels when abstraction was increased by 50% under RCP 8.5 resulting to a decrease in groundwater levels by 1 m around the coast to 7 m towards the northern part of the study area. This further cause a change in the aquifer storage to decrease by 325,000 m3/day and groundwater levels to decrease from a range of 1 to 27 m, respectively. The findings in this study shows that interconnected surface water-groundwater modelling of climate change impacts is critical as predicted change in the surface flow and water levels will affect the regional groundwater budget of the aquifer.
The findings from this study shows that understanding climate changes impacts on both surface and groundwater resources is crucial for the water resources management of any region. Associating climate scenarios, hydrologic modeling and numerical groundwater modeling of aquifers provides useful insight into the future hydrogeological systems interactions, which can be used to envisage measurements of adaptation and protection of the water resources. For the coastal aquifer of Niger Delta, the study shows that the risk of contamination of this system by rivers is high. It is recommended that end-users should reflect on the results of this study during IWRM planning to preserve the long-term exploitation of this aquifer, and as part of the sustainable management of the local and national water resources.Climate change impact studies are challenging in developing countries due to the paucity of climatological datasets resulting from insufficient monitoring stations, and constraint in human and computational resources. The Niger Delta region is one of the most vulnerable and densely populated regions in Nigeria, which presents special challenges for water resource policy and management due to climate change and anthropogenic activities, especially with an increase in water demands. Flooding events are recorded annually in settlements along River Niger and its tributaries, inundating many towns, displacing people from their homes and polluting the surface and groundwater resources. As the surface and groundwater resources are two interconnected components of one single resource, any negative impacts on one will inevitably affect the quantity or quality of the other component. The increase in intense stress on the groundwater from shallow coastal plain sand aquifers as the significant source of water resources for domestic, industrial and agricultural purposes in the area. This study, therefore, presents a novel approach for climate change impact assessment on surface and groundwater resources in developing countries.
The first stage of this study assessed the performance of three widely used daily gridded precipitation (prcp), maximum and minimum temperature (Tmax and Tmin) datasets from the Climatic Research Unit (CRU), Princeton University Global Meteorological Forcing (PGF) and Climate Forecast System Reanalysis (CFSR) datasets available over the Niger Delta part of Nigeria against the observed station datasets to select the best datasets that can serve as a possible replacement to the observed datasets. Symmetrical uncertainty (SU) filter was employed together with the selected hydro-climatological datasets to assess the performance of 26 Coupled Model Intercomparison Project Phase 5 (CMIP5) general circulation model (GCM) outputs. The selection was made according to their capability to simulate observed daily precipitation (prcp), maximum and minimum temperature (Tmax and Tmin) over the historical period 1980โ2005 (Baseline periods) in the Niger Delta region. The selected GCMs were used for climate change predictions and impacts assessment over the period 2020s (2010โ2039), 2050s (2040โ2069) and 2080s (2070โ2099), under Representative Concentration Pathway (RCP) 4.5 and 8.5. Standardized precipitation index (SPI) of 1-month and 12-month time steps were used for extreme event assessment. SWAT (Soil and Water Assessment Tool) model was used to analyse the effects of climate change on the hydrologic processes of the Niger River Basin (NRB) in Nigeria. The hydrostratigraphy of the Niger Delta shallow coastal aquifers was characterised coupled with the simulated aquifer recharge and evapotranspiration deduced from Global Climate Model (GCM) simulations under two Representative concentration pathways (RCP4.5 and RCP8.5) to develop a transient groundwater flow model to investigate the potential impacts of climate change and increased groundwater abstraction on the coastal plain sand aquifer over the periods 2010 to 2099.
Results of the hydro-climatological study revealed that the CRU datasets performed better in most of the statistical assessments conducted. The symmetrical uncertainty filter revealed the four top-ranked GCMs, namely ACCESS1.3, MIROCESM, MIROC-ESM-CHM, and NorESM1-M as the best set of GCMs to form an
ensemble for the Spatio-temporal climate projection over the study area. The selected GCM ensemble predicted an increase in the mean annual precipitation in the range of 0.26% to 3.57% under RCP4.5, and 0.7% to 4.94% under RCP 8.5 by the end of the century as compared to the base period. The study also revealed an increase in maximum temperature in the range of 0 to 0.4 ยฐC under RCP4.5 and 1.25โ1.79 ยฐC under RCP8.5 during the periods 2080s. Minimum temperature also revealed a significant increase of 0 to 0.52 ยฐC under RCP4.5 and between 1.38โ2.02 ยฐC under RCP8.5, which indicates that there might be the occurrence of extreme events in the Niger Delta due to climate change. The 1-month and 12-month SPI under both RCPs predict incidences of extreme wet cycle across all the study locations, especially during the 2080s. The mean annual streamflow was also predicted to increase from 21% to 48% at the Onitsha gauging station under both emission scenarios.
Results of hydrostratigraphic studies revealed that the system was more complicated than previously reported. A unit of silty sand was observed in the western part of the basin, which thins out leaving the eastern part of the basin as an unconfined aquifer underlain by multiple thin beds of the sand aquifer and a layered sand aquifer, which holds freshwater occurring in the northern parts of the basin. Transient groundwater flow model simulations of Port-Harcourt metropolis predicted the maximum change in groundwater budget and levels when abstraction was increased by 50% under RCP 8.5 resulting to a decrease in groundwater levels by 1 m around the coast to 7 m towards the northern part of the study area. This further cause a change in the aquifer storage to decrease by 325,000 m3/day and groundwater levels to decrease from a range of 1 to 27 m, respectively. The findings in this study shows that interconnected surface water-groundwater modelling of climate change impacts is critical as predicted change in the surface flow and water levels will affect the regional groundwater budget of the aquifer.
The findings from this study shows that understanding climate changes impacts on both surface and groundwater resources is crucial for the water resources management of any region. Associating climate scenarios, hydrologic modeling and numerical groundwater modeling of aquifers provides useful insight into the future hydrogeological systems interactions, which can be used to envisage measurements of adaptation and protection of the water resources. For the coastal aquifer of Niger Delta, the study shows that the risk of contamination of this system by rivers is high. It is recommended that end-users should reflect on the results of this study during IWRM planning to preserve the long-term exploitation of this aquifer, and as part of the sustainable management of the local and national water resources
Application of machine learning methods for design of crystallisation processes
Get PDFThere is great potential for the implementation of machine learning to aid in pharmaceutical process development. Machine learning (ML) algorithms can be applied to increase the speed with which high-value drug products are developed for the market while reducing the utilisation of material, minimising wastage and assuring the desired quality attributes are achieved. This thesis illustrates the application of ML techniques in aspects of crystallisation process design assessing the ability to predict crystallisation outcomes, including crystal habit and non-aqueous solubility of pharmaceutical drugs in a diverse range of solvents.;High throughput screening for analysing crystallisation outcomes and crystal habit of paracetamol in a diverse range of solvents was developed using Technobis Crystalline. Out of 94 solvents, paracetamol was observed to crystallise in 44 solvents, remain in solution at set conditions in 11 solvents, never solubilise in 36 solvents and show signs of degradation in 3 solvents. Based on these experimental data, a ML classification model was constructed for predicting the crystallisation outcomes and crystal habit of paracetamol with ~77.78 % prediction accuracy.;Analysis of the ML model revealed that the physicochemical descriptors and predictive capabilities were more directed towards defining solubility of paracetamol rather than its nucleation behaviour. A rapid and efficient solvent selection tool based on relative solubility was developed using ML algorithms. The tool was not only successful in aid of rational selection of solvent but also reduce the number of screening experiments in the laboratory and thus limit material cost and usage.;The regression and classification models built to predict non-aqueous solubility on 247 drug and drug-like molecules in seven commonly used solvents demonstrated that the molecular descriptors calculated using MOE were better at predicting solubility compared to structural fingerprint descriptors. Furthermore, both the regression and classification models successful predicted solubility of drugs in alcohols compared to other organic solvents.There is great potential for the implementation of machine learning to aid in pharmaceutical process development. Machine learning (ML) algorithms can be applied to increase the speed with which high-value drug products are developed for the market while reducing the utilisation of material, minimising wastage and assuring the desired quality attributes are achieved. This thesis illustrates the application of ML techniques in aspects of crystallisation process design assessing the ability to predict crystallisation outcomes, including crystal habit and non-aqueous solubility of pharmaceutical drugs in a diverse range of solvents.;High throughput screening for analysing crystallisation outcomes and crystal habit of paracetamol in a diverse range of solvents was developed using Technobis Crystalline. Out of 94 solvents, paracetamol was observed to crystallise in 44 solvents, remain in solution at set conditions in 11 solvents, never solubilise in 36 solvents and show signs of degradation in 3 solvents. Based on these experimental data, a ML classification model was constructed for predicting the crystallisation outcomes and crystal habit of paracetamol with ~77.78 % prediction accuracy.;Analysis of the ML model revealed that the physicochemical descriptors and predictive capabilities were more directed towards defining solubility of paracetamol rather than its nucleation behaviour. A rapid and efficient solvent selection tool based on relative solubility was developed using ML algorithms. The tool was not only successful in aid of rational selection of solvent but also reduce the number of screening experiments in the laboratory and thus limit material cost and usage.;The regression and classification models built to predict non-aqueous solubility on 247 drug and drug-like molecules in seven commonly used solvents demonstrated that the molecular descriptors calculated using MOE were better at predicting solubility compared to structural fingerprint descriptors. Furthermore, both the regression and classification models successful predicted solubility of drugs in alcohols compared to other organic solvents
Mathematical aspects of coagulation and fragmentation processes
Get PDFIn this thesis, we develop a number of approaches to investigate coagulation and fragmentation processes. We initially use visibility graphs as a tool to analyse the results of kinetic Monte Carlo (kMC) simulations of submonolayer deposition in a one dimensional point island model. We introduce an effcient algorithm for the computation of the visibility graph resulting from a kMC simulation and show that from the properties of the visibility graph one can determine the critical island size, thus demonstrating that the visibility graph approach, which combines island size and spatial distribution data, can provide insights into island nucleation and growth mechanisms. We then consider the dynamics of point islands during submonolayer deposition, in which the fragmentation of subcritical size islands is allowed. To understand asymptotics of solutions, we use methods of centre manifold theory, and for globalisation, we employ results from the theories of compartmental systems and of asymptotically autonomous dynamical systems. We also compare our results with those obtained by making the quasi-steady state assumption. Finally, we demonstrate the versatility of the coagulation-fragmentation framework by considering the asymptotics of the average Erdos number. We also compare our results with those obtained by using a Gillespie type algorithm.In this thesis, we develop a number of approaches to investigate coagulation and fragmentation processes. We initially use visibility graphs as a tool to analyse the results of kinetic Monte Carlo (kMC) simulations of submonolayer deposition in a one dimensional point island model. We introduce an effcient algorithm for the computation of the visibility graph resulting from a kMC simulation and show that from the properties of the visibility graph one can determine the critical island size, thus demonstrating that the visibility graph approach, which combines island size and spatial distribution data, can provide insights into island nucleation and growth mechanisms. We then consider the dynamics of point islands during submonolayer deposition, in which the fragmentation of subcritical size islands is allowed. To understand asymptotics of solutions, we use methods of centre manifold theory, and for globalisation, we employ results from the theories of compartmental systems and of asymptotically autonomous dynamical systems. We also compare our results with those obtained by making the quasi-steady state assumption. Finally, we demonstrate the versatility of the coagulation-fragmentation framework by considering the asymptotics of the average Erdos number. We also compare our results with those obtained by using a Gillespie type algorithm
Designing, developing and evaluating an age-appropriate digital educational tool for younger children with Type-1 Diabetes
Get PDFYounger children (under 9 years old) with type-1 diabetes are often very passive in the management of their condition and can face difficulties in accessing basic information about their condition. This can make transitioning to self-management in later years very challenging. Previous research has mostly focused on educational interventions for older children who have literacy skills. In order to create an educational tool that can effectively support the education of younger children with diabetes and be feasible for adoption in the local context, we conducted a multiphase and multi-stakeholder human-centred design process.;The process entailed a review of the relevant literature, in-context qualitative enquiries for requirements gathering, an iterative design process with stakeholder participation, multiple prototyping and evaluation stages, development and a final large-scale evaluation. The result of this process is an interactive digital tool that illustrates diabetes concepts in an age-appropriate way with the use of tangible toys as input devices. The tool was evaluated in-context with children, parents and clinicians against the stakeholders' requirements.;The results showed the effectiveness of the tool in enabling clinicians to convey the educational message in a fun, age-appropriate and memorable way.The results also informed about the feasibility of the tool to be adopted in standard practice. This thesis illustrates in detail the aforementioned process and its results and also syntheses the findings in order to inform more generally the design and development of other educational tools for younger children with complex educational needs.Younger children (under 9 years old) with type-1 diabetes are often very passive in the management of their condition and can face difficulties in accessing basic information about their condition. This can make transitioning to self-management in later years very challenging. Previous research has mostly focused on educational interventions for older children who have literacy skills. In order to create an educational tool that can effectively support the education of younger children with diabetes and be feasible for adoption in the local context, we conducted a multiphase and multi-stakeholder human-centred design process.;The process entailed a review of the relevant literature, in-context qualitative enquiries for requirements gathering, an iterative design process with stakeholder participation, multiple prototyping and evaluation stages, development and a final large-scale evaluation. The result of this process is an interactive digital tool that illustrates diabetes concepts in an age-appropriate way with the use of tangible toys as input devices. The tool was evaluated in-context with children, parents and clinicians against the stakeholders' requirements.;The results showed the effectiveness of the tool in enabling clinicians to convey the educational message in a fun, age-appropriate and memorable way.The results also informed about the feasibility of the tool to be adopted in standard practice. This thesis illustrates in detail the aforementioned process and its results and also syntheses the findings in order to inform more generally the design and development of other educational tools for younger children with complex educational needs
Mental health among young workers, the impact of job quality
Get PDFYouth employment is becoming increasingly more difficult and diversified. Today many young adults (18-34) live under precarious employment conditions (e.g. temporary / part-time), have problems in finding stable employment, are underemployed (e.g. not well-matched to their jobs in terms of skills and / or working hours), and many are stuck in low quality jobs with few opportunities to move up the employment ladder. These difficult working life experiences create a risk that the way young adults experience work in contemporary labour markets may undermine their basic psychological needs for control, security and autonomy. To date, the information surrounding issues of job quality and mental health among this particularly disadvantaged and vulnerable population has been scarce, and often limited to earnings and employment status as an indication of how well young individuals fare in paid work. The overarching aim of this study is to examine job quality, its determinants and mental health outcomes among young workers in contemporary labour markets. To address this aim, this study uses a secondary research design. Three large-scale social surveys are used to examine research objectives and hypotheses: (1) the European Working Conditions Survey (2015); (2) the European Social Survey (2010); and (3) the UK Labour Force Survey (2017). The focus of this study is on the UK context, which has been shown to have high rates of youth underemployment and a large proportion of young people employed in precarious forms of employment. For hypotheses related to the role of institutional context in affecting job quality and mental health, three other European countries (Denmark, Germany and Spain) are included. Young workers aged 18-34 are considered due to increasingly longer transitions to employment and adulthood in contemporary labour markets which often extend into early 30s. The findings point to the salience of job quality in the youth context and the importance of a holistic approach, which considers intrinsic aspects of work and contextual factors. Examining the outcomes of job quality in terms of mental health further emphasises the importance of job quality for young people and indicate that, in addition to the need for work to be good in terms of more universal aspects (such as high social support), the impact of job quality on mental health depends on the extent to which jobs are in line with young workers' abilities and needs. In relation to this, perceived employability is found to be an important personal resource in the youth context, which may help to alleviate the negative effects of being in undesirable employment. This study has important policy implications and makes theoretical contributions in relation to our understanding of job quality in the youth context, its determinants and mental health outcomes.Youth employment is becoming increasingly more difficult and diversified. Today many young adults (18-34) live under precarious employment conditions (e.g. temporary / part-time), have problems in finding stable employment, are underemployed (e.g. not well-matched to their jobs in terms of skills and / or working hours), and many are stuck in low quality jobs with few opportunities to move up the employment ladder. These difficult working life experiences create a risk that the way young adults experience work in contemporary labour markets may undermine their basic psychological needs for control, security and autonomy. To date, the information surrounding issues of job quality and mental health among this particularly disadvantaged and vulnerable population has been scarce, and often limited to earnings and employment status as an indication of how well young individuals fare in paid work. The overarching aim of this study is to examine job quality, its determinants and mental health outcomes among young workers in contemporary labour markets. To address this aim, this study uses a secondary research design. Three large-scale social surveys are used to examine research objectives and hypotheses: (1) the European Working Conditions Survey (2015); (2) the European Social Survey (2010); and (3) the UK Labour Force Survey (2017). The focus of this study is on the UK context, which has been shown to have high rates of youth underemployment and a large proportion of young people employed in precarious forms of employment. For hypotheses related to the role of institutional context in affecting job quality and mental health, three other European countries (Denmark, Germany and Spain) are included. Young workers aged 18-34 are considered due to increasingly longer transitions to employment and adulthood in contemporary labour markets which often extend into early 30s. The findings point to the salience of job quality in the youth context and the importance of a holistic approach, which considers intrinsic aspects of work and contextual factors. Examining the outcomes of job quality in terms of mental health further emphasises the importance of job quality for young people and indicate that, in addition to the need for work to be good in terms of more universal aspects (such as high social support), the impact of job quality on mental health depends on the extent to which jobs are in line with young workers' abilities and needs. In relation to this, perceived employability is found to be an important personal resource in the youth context, which may help to alleviate the negative effects of being in undesirable employment. This study has important policy implications and makes theoretical contributions in relation to our understanding of job quality in the youth context, its determinants and mental health outcomes
Geopolymer-based moisture and chloride sensors for nuclear concrete structures
Get PDFThe reinforced concrete structures that support transport, energy and urban networks in developed countries are over half a century old, and are facing widespread deterioration. The main cause of degradation - reinforcement corrosion, accelerated by moisture and chloride exposure - costs the global economy a staggering {dollar}2.3 trillion per year (3.4% GDP, 2013). The nuclear industry faces a particular challenge, as concrete assets are usually coastal and can underpin safety-critical structures and radiation barriers. Passively-cooled waste stores, for example, are often ventilated with unfiltered sea air.To deliver structural health monitoring and maintenance strategies, industry requires both moisture/chloride sensors and concrete repair materials. To date, monitoring and maintenance have been viewed as separate challenges. The work in this thesis demonstrates that geopolymer binders - a class of adhesive concrete repair materials - can be electrically interrogated and used to monitor moisture and chloride concentrations on concrete surfaces, or as stand-alone sensors. This can be achieved without sacrificing the ability of the geopolymer to form an effective repair.This thesis outlines first-time demonstrations of moisture and chloride sensors based on fly ash geopolymers, and the fabrication of additive-free, ambient-cured, non-structural geopolymer repairs. In achieving these aims, the work demonstrates that affordable, combined monitoring and maintenance technologies for concrete can be delivered. Reducing the number of steps in deploying repairs and sensors will allow more of our ageing concrete infrastructure to be updated and repaired, so that it can meet modern expectations of safety, and remain resilient in the face of climate change.The reinforced concrete structures that support transport, energy and urban networks in developed countries are over half a century old, and are facing widespread deterioration. The main cause of degradation - reinforcement corrosion, accelerated by moisture and chloride exposure - costs the global economy a staggering {dollar}2.3 trillion per year (3.4% GDP, 2013). The nuclear industry faces a particular challenge, as concrete assets are usually coastal and can underpin safety-critical structures and radiation barriers. Passively-cooled waste stores, for example, are often ventilated with unfiltered sea air.To deliver structural health monitoring and maintenance strategies, industry requires both moisture/chloride sensors and concrete repair materials. To date, monitoring and maintenance have been viewed as separate challenges. The work in this thesis demonstrates that geopolymer binders - a class of adhesive concrete repair materials - can be electrically interrogated and used to monitor moisture and chloride concentrations on concrete surfaces, or as stand-alone sensors. This can be achieved without sacrificing the ability of the geopolymer to form an effective repair.This thesis outlines first-time demonstrations of moisture and chloride sensors based on fly ash geopolymers, and the fabrication of additive-free, ambient-cured, non-structural geopolymer repairs. In achieving these aims, the work demonstrates that affordable, combined monitoring and maintenance technologies for concrete can be delivered. Reducing the number of steps in deploying repairs and sensors will allow more of our ageing concrete infrastructure to be updated and repaired, so that it can meet modern expectations of safety, and remain resilient in the face of climate change
Exploring the application of lean manufacturing best practices in the remanufacturing context
Get PDFContinued strains on the planet's resources, limited sites for product disposal and the introduction of new environmental legislation have resulted in a growing interest in material and product recovery options. The remanufacturing process is rated as one of the most promising and cost-effective options which can bring back end-of-life products to an as-good-as-new condition in terms of quality, performance, and warranty (Ijomah et al., 2007). However, the process is more complex than traditional manufacturing and researchers have identified several difficulties that make process planning and control (PPC) more difficult in remanufacturing environments.;For example, the degree of automation is usually lower and consequently, the amount of manual work is higher. Moreover remanufacturing facilities struggle not only with relatively high inventories of cores and finished product but also with inventories in between processes. Such issues impact negatively on remanufacturing performance measures like lead-time and costs. A system that will help to reduce cost, improve productivity and gain a competitive advantage is required. Previous research has confirmed that the combination of remanufacturing with lean manufacturing best practices appears to offer a good opportunity to increase process efficiencies within this type of industry.;Since Lean remanufacturing is still a novel field and there is a paucity of data and publications multiple case studies are used to gain insight into industrial activities and the performance of remanufacturing operations. Three case companies (two British and one Polish) operating within the remanufacturing industry were investigated. The study focuses on the automotive industry, which often demonstrates a greater understanding of lean thinking and practice, giving the opportunity to collect sufficient information to progress the research.;A key contribution of this research is the identification of lean practices that help manage the complexity in the remanufacturing processes thus improving general remanufacturing. This study confirmed that lean practices such as standardisation, Kanban, Cross-functional workforce, production analysis board, 5S, visual management, cellular manufacturing and TPM help manage the negative effect of the inherent complexities of the remanufacturing process. An Opportunities Matrix has been developed so that the findings can be more easily used by industry. Moreover, factors that limit the application of Lean practices within remanufacturing were also discussed.;This research confirmed that the complexities of the remanufacturing process such as stochastic routings for material for remanufacturing operations, uncertainty in materials recovered from returned items, highly variable processing time and the complication of material matching restrictions limit the application of FIFO, standardised work instructions, Kanban, cellular manufacturing. A Threats Matrix has also been developed to visualise the research findings. Both academic and industry benefit from this research. Remanufacturing companies can use this study to choose suitable lean practices for addressing challenges that are facing. Further research should be focused on the particular lean tools that are identified in this research as difficult or impossible to implement in remanufacturing.Continued strains on the planet's resources, limited sites for product disposal and the introduction of new environmental legislation have resulted in a growing interest in material and product recovery options. The remanufacturing process is rated as one of the most promising and cost-effective options which can bring back end-of-life products to an as-good-as-new condition in terms of quality, performance, and warranty (Ijomah et al., 2007). However, the process is more complex than traditional manufacturing and researchers have identified several difficulties that make process planning and control (PPC) more difficult in remanufacturing environments.;For example, the degree of automation is usually lower and consequently, the amount of manual work is higher. Moreover remanufacturing facilities struggle not only with relatively high inventories of cores and finished product but also with inventories in between processes. Such issues impact negatively on remanufacturing performance measures like lead-time and costs. A system that will help to reduce cost, improve productivity and gain a competitive advantage is required. Previous research has confirmed that the combination of remanufacturing with lean manufacturing best practices appears to offer a good opportunity to increase process efficiencies within this type of industry.;Since Lean remanufacturing is still a novel field and there is a paucity of data and publications multiple case studies are used to gain insight into industrial activities and the performance of remanufacturing operations. Three case companies (two British and one Polish) operating within the remanufacturing industry were investigated. The study focuses on the automotive industry, which often demonstrates a greater understanding of lean thinking and practice, giving the opportunity to collect sufficient information to progress the research.;A key contribution of this research is the identification of lean practices that help manage the complexity in the remanufacturing processes thus improving general remanufacturing. This study confirmed that lean practices such as standardisation, Kanban, Cross-functional workforce, production analysis board, 5S, visual management, cellular manufacturing and TPM help manage the negative effect of the inherent complexities of the remanufacturing process. An Opportunities Matrix has been developed so that the findings can be more easily used by industry. Moreover, factors that limit the application of Lean practices within remanufacturing were also discussed.;This research confirmed that the complexities of the remanufacturing process such as stochastic routings for material for remanufacturing operations, uncertainty in materials recovered from returned items, highly variable processing time and the complication of material matching restrictions limit the application of FIFO, standardised work instructions, Kanban, cellular manufacturing. A Threats Matrix has also been developed to visualise the research findings. Both academic and industry benefit from this research. Remanufacturing companies can use this study to choose suitable lean practices for addressing challenges that are facing. Further research should be focused on the particular lean tools that are identified in this research as difficult or impossible to implement in remanufacturing
Development of exosome-based anti-cancer therapeutics
Get PDFHepatocellular carcinoma (HCC) exosomes are found to be responsible for cancer progression, metastasis, and angiogenesis via cellular communications. However, studying cancer derived exosomes in vitro is limited, due to the way cell lines are grown in medium supplemented with foetal bovine serum (FBS) that contains naturally occurring exosomes. Bovine-derived exosomes can cause artefacts and interfere with interpretation of results. The aim of this study was to investigate the release of exosomes from human liver cancer cell line HepG2 (HepG2-Exo) under different conditioned media with modified FBS to deliver the best approach for exosome production. Thus, two media were developed for growing HepG2 cell line which are M1 and M2 using dulbecco's modified eagle medium (DMEM), where M1 supplemented with 10 % (v/v) FBS, and M2 with 10 % (v/v) exosome depleted FBS (Dep-FBS). However, after cells reached confluency, those two media were removed and replaced with serum free media (only DMEM), to create M3 and M4, respectively. This resulted in collecting four categories of media: M1, M2, M3, and M4. Consequently, four groups of exosomes were obtained (Exo(M1), Exo(M2), Exo(M3), and Exo(M4).;In regard to cell culture, findings confirmed that M2 was the best approach for cultivating HepG2 and collecting exosomes, as cell viability was enhanced and contamination with FBS-exosomes was minimal, compared to M1. However, analysis of the different HepG2-Exo groups showed significant difference in protein concentration, percentage of fluorescence, exosome marker detection, tetraspanins expression, particle count, metabolic and lipidomic profiling, RNA sequencing, and gene expression. This difference indicates that the effect of media composition is inevitable on cell-derived exosome which may cause misinterpretation of the effect of the exosomes of interest. Consequently, biological assessment and metabolomic profiling of HepG2-Exo effect on different cancer and normal cell lines was carried out: A375 (melanoma), A549 (lung cancer), and PNT2A (normal prostate epithelium). The biological assays revealed that HepG2-Exo induced the proliferation, migration, adhesion, and invasion of A549 at 50 ยตg/ml. While metabolome analysis showed that HepG2-Exo at 100 ยตg/ml, induced significant changes in the cell metabolome of A375.;The outcomes of this project provided an effective approach in developing successful cell culture for exosome collection without concern over contamination from FBS-derived exosomes and brought attention to the critical effect of media in exosome studies. Moreover, this project has highlighted the effect of HepG2-Exo on other cell lines and the potential of HepG2-Exo to be applied to the development of future lung cancer therapeutics.Hepatocellular carcinoma (HCC) exosomes are found to be responsible for cancer progression, metastasis, and angiogenesis via cellular communications. However, studying cancer derived exosomes in vitro is limited, due to the way cell lines are grown in medium supplemented with foetal bovine serum (FBS) that contains naturally occurring exosomes. Bovine-derived exosomes can cause artefacts and interfere with interpretation of results. The aim of this study was to investigate the release of exosomes from human liver cancer cell line HepG2 (HepG2-Exo) under different conditioned media with modified FBS to deliver the best approach for exosome production. Thus, two media were developed for growing HepG2 cell line which are M1 and M2 using dulbecco's modified eagle medium (DMEM), where M1 supplemented with 10 % (v/v) FBS, and M2 with 10 % (v/v) exosome depleted FBS (Dep-FBS). However, after cells reached confluency, those two media were removed and replaced with serum free media (only DMEM), to create M3 and M4, respectively. This resulted in collecting four categories of media: M1, M2, M3, and M4. Consequently, four groups of exosomes were obtained (Exo(M1), Exo(M2), Exo(M3), and Exo(M4).;In regard to cell culture, findings confirmed that M2 was the best approach for cultivating HepG2 and collecting exosomes, as cell viability was enhanced and contamination with FBS-exosomes was minimal, compared to M1. However, analysis of the different HepG2-Exo groups showed significant difference in protein concentration, percentage of fluorescence, exosome marker detection, tetraspanins expression, particle count, metabolic and lipidomic profiling, RNA sequencing, and gene expression. This difference indicates that the effect of media composition is inevitable on cell-derived exosome which may cause misinterpretation of the effect of the exosomes of interest. Consequently, biological assessment and metabolomic profiling of HepG2-Exo effect on different cancer and normal cell lines was carried out: A375 (melanoma), A549 (lung cancer), and PNT2A (normal prostate epithelium). The biological assays revealed that HepG2-Exo induced the proliferation, migration, adhesion, and invasion of A549 at 50 ยตg/ml. While metabolome analysis showed that HepG2-Exo at 100 ยตg/ml, induced significant changes in the cell metabolome of A375.;The outcomes of this project provided an effective approach in developing successful cell culture for exosome collection without concern over contamination from FBS-derived exosomes and brought attention to the critical effect of media in exosome studies. Moreover, this project has highlighted the effect of HepG2-Exo on other cell lines and the potential of HepG2-Exo to be applied to the development of future lung cancer therapeutics
Development of a novel combination radio- chemotherapy for glioblastoma multiforme
Get PDFGlioblastoma multiforme is an invariably terminal cancer, with 5-year survival rates as low as 1.9% in some patient groups. The current treatment for glioblastoma is surgery, external beam radiotherapy and adjuvant and concomitant temozolomide chemotherapy. Treatment will fail due to an inherent treatment resistance, and as aresult, current treatment for glioblastoma has been designated as an unmet clinical need, meaning that new and more efficacious treatment options are needed. Dimethyl fumarate is a clinically available immunomodulatory drug, currently used to treat multiple sclerosis.;One of the targets of dimethyl fumarate is glutathione, a potent chemo- and radio-resistance factor. We hypothesised that the use of dimethyl fumarate as an adjuvant to standard of care chemo-radiotherapy would increase the efficacy of treatment via glutathione inhibition and subsequent amplification of chemo-radiotherapy effects on a molecular level. We have shown, using bespoke combinations of temozolomide and dimethyl fumarate in two glioblastoma cell lines, that our hypothesis was correct. Cell line specific combinations of temozolomide and dimethyl fumarate significantly increased cell kill in a dose dependent manner.;Unfortunately, a precise mechanism for this combination was unable to be elucidated. There was no significant increase in DNA double strand breaks, cell cycle arrest or apoptotic induction when temozolomide treatment and X-irradiation was combined with dimethyl fumarate. We were able to positively identify glutathione as a chemoresistance factor in these cell lines, as well as rule out the role of reactive oxygen species. We have also shown however, that dimethyl fumarate is capable of activating the chemo- and radioresistance factorNRF2. We believe that this is the first mechanistic interrogation of dimethyl fumarate being used to potentiate combined chemo-radiotherapy, however future work is needed before potential clinical deployment of dimethyl fumarate as an anti-neoplastic agent.Glioblastoma multiforme is an invariably terminal cancer, with 5-year survival rates as low as 1.9% in some patient groups. The current treatment for glioblastoma is surgery, external beam radiotherapy and adjuvant and concomitant temozolomide chemotherapy. Treatment will fail due to an inherent treatment resistance, and as aresult, current treatment for glioblastoma has been designated as an unmet clinical need, meaning that new and more efficacious treatment options are needed. Dimethyl fumarate is a clinically available immunomodulatory drug, currently used to treat multiple sclerosis.;One of the targets of dimethyl fumarate is glutathione, a potent chemo- and radio-resistance factor. We hypothesised that the use of dimethyl fumarate as an adjuvant to standard of care chemo-radiotherapy would increase the efficacy of treatment via glutathione inhibition and subsequent amplification of chemo-radiotherapy effects on a molecular level. We have shown, using bespoke combinations of temozolomide and dimethyl fumarate in two glioblastoma cell lines, that our hypothesis was correct. Cell line specific combinations of temozolomide and dimethyl fumarate significantly increased cell kill in a dose dependent manner.;Unfortunately, a precise mechanism for this combination was unable to be elucidated. There was no significant increase in DNA double strand breaks, cell cycle arrest or apoptotic induction when temozolomide treatment and X-irradiation was combined with dimethyl fumarate. We were able to positively identify glutathione as a chemoresistance factor in these cell lines, as well as rule out the role of reactive oxygen species. We have also shown however, that dimethyl fumarate is capable of activating the chemo- and radioresistance factorNRF2. We believe that this is the first mechanistic interrogation of dimethyl fumarate being used to potentiate combined chemo-radiotherapy, however future work is needed before potential clinical deployment of dimethyl fumarate as an anti-neoplastic agent
A novel configuration of all-optical differential protection scheme
Get PDFAdvantages of the optical current sensing techniques have stimulated the development of the optical differential protection schemes for busbar protection. However, these optical differential schemes adopt mixed optical-numerical processes that use a platform based on modern numerical/microprocessor protection schemes. Therefore, opportunities to improve these mixed optical-numerical protection schemes still exist. This thesis proposes a novel configuration to perform an optical differential protection scheme that is implemented using a designed arrangement of basic optical components. In this design, the inherent operational functionality of the current differential connection is realised in the optical domain with a designed configuration of optical components. Due to the purely optical nature of the scheme, the need for complex numerical processing, which consists of direct digitisation of the output from individual sensors followed by digital signal processing within the relay, is eliminated. Therefore, the designed scheme could minimize the differential protection complexity while retaining the quality of the differential scheme. Moreover, it has also the potential for a significant reduction in the protection operating time. To verify and validate the optical configuration, one model is proposed, but simulated with different components and validated by simulation and experiment. The simulation results show that, firstly, the proposed scheme is verified, and both of the model and configurations are correct. Secondly, the proposed optical system which uses the polarization-maintaining optical fibre as fibre links has successfully met the protection performance objectives with respect to sensitivity (dependability), security, and speed of operation. Furthermore, a prototype of the proposed scheme has been constructed, and the obtained empirical data further validated the outcome from the simulation models. The validation by the empirical data provided, first, the proposed arrangement of the optical components were correctly configured, and the models of the optical components were correctly represented. Second, the experimental data have been successfully predicted by the simulation models. Finally, the proposed scheme prototype achieved good discrimination necessary for protection purposes.Advantages of the optical current sensing techniques have stimulated the development of the optical differential protection schemes for busbar protection. However, these optical differential schemes adopt mixed optical-numerical processes that use a platform based on modern numerical/microprocessor protection schemes. Therefore, opportunities to improve these mixed optical-numerical protection schemes still exist. This thesis proposes a novel configuration to perform an optical differential protection scheme that is implemented using a designed arrangement of basic optical components. In this design, the inherent operational functionality of the current differential connection is realised in the optical domain with a designed configuration of optical components. Due to the purely optical nature of the scheme, the need for complex numerical processing, which consists of direct digitisation of the output from individual sensors followed by digital signal processing within the relay, is eliminated. Therefore, the designed scheme could minimize the differential protection complexity while retaining the quality of the differential scheme. Moreover, it has also the potential for a significant reduction in the protection operating time. To verify and validate the optical configuration, one model is proposed, but simulated with different components and validated by simulation and experiment. The simulation results show that, firstly, the proposed scheme is verified, and both of the model and configurations are correct. Secondly, the proposed optical system which uses the polarization-maintaining optical fibre as fibre links has successfully met the protection performance objectives with respect to sensitivity (dependability), security, and speed of operation. Furthermore, a prototype of the proposed scheme has been constructed, and the obtained empirical data further validated the outcome from the simulation models. The validation by the empirical data provided, first, the proposed arrangement of the optical components were correctly configured, and the models of the optical components were correctly represented. Second, the experimental data have been successfully predicted by the simulation models. Finally, the proposed scheme prototype achieved good discrimination necessary for protection purposes
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