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A qualitative analysis of students' naturalistic learning processes during their first experience in problem-based learning
Get PDFFuture global challenges that engineering graduates face have placed demands on engineering education and how graduates develop professional skills while studying at university. Such demand has seen an increase in the use of pedagogies like problem-based learning (PBL) that provide opportunities for developing professional skills such as teamwork and problem-solving.;The current research in PBL is maifocused on evaluatingnly the pedagogy on a curricula scale rather than the collaborative processes involved in such a student-centred and active pedagogy.;This thesis is aiming to address this and gain an insight and understanding of students' naturalistic learning processes during their very first experience with problem-based learning (PBL); to identify strategies which are used by team members to manage the PBL process.;This has been successfully investigated through analysis of naturalistic observations of students in PBL sessions. The thesis reports the analysis of 80 hours of naturalistic video data collected from students, studying at the University of Strathclyde, during their PBL sessions. This data was then analysed using qualitative content analysis, a method that enabled the author to identify and describe strategies observed in the video data using a systematic and scientific approach.;The strategies identified indicate that the students are not conducting PBL sessions as they are designed or intended to be held, particularly when the teams are managing their own group processes. The findings of this study emphasize just how complicated it can be to transition from a passive learning role (e.g. during lectures) to an active role (e.g. in PBL), where the responsibility of learning is with the students themselves.;The study highlights how video recording data can be used to provide a novel contribution to the research on problem-based learning in engineering education and broaden the understanding of strategies used by students to manage the problem-based learning process.Future global challenges that engineering graduates face have placed demands on engineering education and how graduates develop professional skills while studying at university. Such demand has seen an increase in the use of pedagogies like problem-based learning (PBL) that provide opportunities for developing professional skills such as teamwork and problem-solving.;The current research in PBL is maifocused on evaluatingnly the pedagogy on a curricula scale rather than the collaborative processes involved in such a student-centred and active pedagogy.;This thesis is aiming to address this and gain an insight and understanding of students' naturalistic learning processes during their very first experience with problem-based learning (PBL); to identify strategies which are used by team members to manage the PBL process.;This has been successfully investigated through analysis of naturalistic observations of students in PBL sessions. The thesis reports the analysis of 80 hours of naturalistic video data collected from students, studying at the University of Strathclyde, during their PBL sessions. This data was then analysed using qualitative content analysis, a method that enabled the author to identify and describe strategies observed in the video data using a systematic and scientific approach.;The strategies identified indicate that the students are not conducting PBL sessions as they are designed or intended to be held, particularly when the teams are managing their own group processes. The findings of this study emphasize just how complicated it can be to transition from a passive learning role (e.g. during lectures) to an active role (e.g. in PBL), where the responsibility of learning is with the students themselves.;The study highlights how video recording data can be used to provide a novel contribution to the research on problem-based learning in engineering education and broaden the understanding of strategies used by students to manage the problem-based learning process
Engineering Streptomyces clavuligerus for efficient growth on sustainable carbon sources
Get PDFThis thesis was previously held under moratorium from 30/03/2021 to 03/04/2024Streptomyces clavuligerus is the industrial producer of the β-lactamase inhibitor, clavulanic acid (CA). This compound is one of the components of the co-formulation generically known as co-amoxiclav. This pharmaceutical combines CA and amoxycillin and is industrially produced by GlaxoSmithKline (GSK), which markets the drug under the trade name Augmentin. The industrial-scale fermentation with S. clavuligerus, the process by which CA is produced by GSK, requires human food-grade and costly carbon sources as feedstocks. To make the industrial production of CA more sustainable and economical, GSK would like to source industrial by-products as feedstocks. Yet, S. clavuligerus has a limited carbon catabolic profile, its preferred carbon source being glycerol, which does not allow the use of alternative sources of carbon, such as glucose. S. clavuligerus was considered naturally glucose auxotrophic due to the lack of a glucose uptake system. In streptomycetes, glucose is transported into the cell via a glucose permease (GlcP) and subsequently phosphorylated by a glucokinase (Glk). Although genes encoding GlcP and Glk, glcP and glk, respectively, are present on the S. clavuligerus genome, expression of the former is too low to enable sufficient uptake of the hexose to support growth. Industrial production strain improvement traditionally involved random mutagenesis and subsequent rounds of selection of strains exhibiting desirable traits, such as improved antibiotic titres. Yet, with this approach, altered phenotypes cannot be linked to changes in genotypes. Therefore, the focus of this thesis was to gain an understanding of carbon utilisation of two industrial strains provided by GSK: SC2 and SC6. Subsequently, a targeted approach to improving glucose utilisation was taken by expressing streptomycete glcP and glk genes. This showed that, contrary to previous reports on CCR in a wildtype background, glucose triggers repression of CA biosynthesis in the earlier production strain. Furthermore, the strains were found to be de-regulated in their production of extracellular proteases, which might affect nutrient uptake and utilisation during fermentation. Protein-protein interaction between GlcP and Glk from S. clavuligerus, further, revealed a lack of interaction. GlcP and Glk are known to interact in S. coelicolor, a glucose utilising streptomycete. Overall, this thesis provides findings of aspects of the central carbon metabolism of an industrially relevant organism. Further, advantages of rational strain improvement are highlighted by heterologous expression of genes of interest and being able to directly link observed phenotypes.Streptomyces clavuligerus is the industrial producer of the β-lactamase inhibitor, clavulanic acid (CA). This compound is one of the components of the co-formulation generically known as co-amoxiclav. This pharmaceutical combines CA and amoxycillin and is industrially produced by GlaxoSmithKline (GSK), which markets the drug under the trade name Augmentin. The industrial-scale fermentation with S. clavuligerus, the process by which CA is produced by GSK, requires human food-grade and costly carbon sources as feedstocks. To make the industrial production of CA more sustainable and economical, GSK would like to source industrial by-products as feedstocks. Yet, S. clavuligerus has a limited carbon catabolic profile, its preferred carbon source being glycerol, which does not allow the use of alternative sources of carbon, such as glucose. S. clavuligerus was considered naturally glucose auxotrophic due to the lack of a glucose uptake system. In streptomycetes, glucose is transported into the cell via a glucose permease (GlcP) and subsequently phosphorylated by a glucokinase (Glk). Although genes encoding GlcP and Glk, glcP and glk, respectively, are present on the S. clavuligerus genome, expression of the former is too low to enable sufficient uptake of the hexose to support growth. Industrial production strain improvement traditionally involved random mutagenesis and subsequent rounds of selection of strains exhibiting desirable traits, such as improved antibiotic titres. Yet, with this approach, altered phenotypes cannot be linked to changes in genotypes. Therefore, the focus of this thesis was to gain an understanding of carbon utilisation of two industrial strains provided by GSK: SC2 and SC6. Subsequently, a targeted approach to improving glucose utilisation was taken by expressing streptomycete glcP and glk genes. This showed that, contrary to previous reports on CCR in a wildtype background, glucose triggers repression of CA biosynthesis in the earlier production strain. Furthermore, the strains were found to be de-regulated in their production of extracellular proteases, which might affect nutrient uptake and utilisation during fermentation. Protein-protein interaction between GlcP and Glk from S. clavuligerus, further, revealed a lack of interaction. GlcP and Glk are known to interact in S. coelicolor, a glucose utilising streptomycete. Overall, this thesis provides findings of aspects of the central carbon metabolism of an industrially relevant organism. Further, advantages of rational strain improvement are highlighted by heterologous expression of genes of interest and being able to directly link observed phenotypes
The principle of proportionality in European and comparative perspective
Get PDFThis thesis critically examines the application of the principle of proportionality in fundamental rights judgments of three courts - the Maltese Constitutional Court, the European Court of Human Rights and the Court of Justice of the European Union - in the light of Robert Alexy's theory of proportionality. The thesis begins by defending Alexy’s three-stage model of proportionality analysis as the most appropriate and effective method of adjudicating conflicts between fundamental rights, or fundamental rights and general interests. However, close examination of the jurisprudence of the three selected courts reveals that each applies a different – and reduced – version of the principle of proportionality. The thesis seeks to explain these variations in terms of the nature of each of the courts, the judicial authority they have developed throughout the years and the nature of the legal system that they serve, which have influenced their juridical mentality, the external considerations they make, the different values they hold and lastly, the different conceptions of proportionality that they have. Nevertheless, it argues that the courts’ deviation from Alexy's model reduces the efficiency and effectiveness of the courts' respective approaches to fundamental rights adjudication and recommends that it is still possible to adhere to this model if they are willing to fine-tuning their conception of the principle of proportionality.This thesis critically examines the application of the principle of proportionality in fundamental rights judgments of three courts - the Maltese Constitutional Court, the European Court of Human Rights and the Court of Justice of the European Union - in the light of Robert Alexy's theory of proportionality. The thesis begins by defending Alexy’s three-stage model of proportionality analysis as the most appropriate and effective method of adjudicating conflicts between fundamental rights, or fundamental rights and general interests. However, close examination of the jurisprudence of the three selected courts reveals that each applies a different – and reduced – version of the principle of proportionality. The thesis seeks to explain these variations in terms of the nature of each of the courts, the judicial authority they have developed throughout the years and the nature of the legal system that they serve, which have influenced their juridical mentality, the external considerations they make, the different values they hold and lastly, the different conceptions of proportionality that they have. Nevertheless, it argues that the courts’ deviation from Alexy's model reduces the efficiency and effectiveness of the courts' respective approaches to fundamental rights adjudication and recommends that it is still possible to adhere to this model if they are willing to fine-tuning their conception of the principle of proportionality
Development of a 1D phased ultrasonic array for intravascular sonoporation
Get PDFSonoporation represents a promising approach to increase targeted drug delivery efficiency by facilitating transport of therapeutic agents to the target tissue with the use of ultrasound. However, most of the current research in sonoporation is performed with external ultrasonic transducers, which hinders the applicability of the therapeutic procedure for treatment of conditions situated deeper into the patient’s body, such as liver or intestinal tumours. This Thesis presents the development process of a miniature-sized 1-3 connectivity piezocomposite 1D phased array for intracorporeal sonoporation. The device was to be incorporated into a capsule or catheter and hence the primary design constraint was the reduced size of the piezoelectric element, which was limited to 2.5 mm in width and 12 mm in length. To meet the needs of the intended application, resonance frequencies of 1.5 MHz and 3.0 MHz were considered. A simulation framework was developed for optimization of the miniature array in relation to the peak negative pressure attained at the focus to mitigate the low power output associated with the limited device dimensions. This was implemented through a multiparametric sweep of the 1-3 piezocomposite geometry-related parameters. Devices made with PZT-5H and PMN-29%PT were evaluated. The optimization algorithm was used to determine specifications for phased array designs based on the two materials and the two resonance frequencies. The 1.5 MHz devices comprised 24 elements and the 3.0 MHz ones had 32 elements. The piezocomposites were manufactured using the dice and fill technique and electroded using a novel method of electrode deposition employing spin coating of Ag ink. Subsequently, the prototype devices were driven with a commercial array controller and characterized with a calibrated needle hydrophone in a scanning tank. Two simulation profiles based on finite element analysis and time extrapolation were developed to model the acoustic beams from the arrays, which were compared and calibrated with experimental data for focal distances between 5 mm and 10 mm and beam steering angles from 0° to 40°. The results showed that modelling could be employed reliably for therapeutic planning. Both the 1.5 MHz and the 3.0 MHz, PZT-5H arrays were tested in vitro and shown to induce and control sonoporation of a human epithelial colorectal adenocarcinoma cell layer. Finally, a 24 element, 1.5 MHz, PZT-5H array was implemented in a 40 mm long by 11 mm diameter tethered, biocompatible capsule intended for in vivo operation. The device was characterized in the scanning tank for steering angles in the range 0° to 56° and focal distances between 4.0 mm and 5.7 mm, and the measured beam profiles were correlated with the simulation framework. The capsule will be tested in future ex-vivo and in-vivo experiments on insulin absorption through porcine small bowel by means of sonoporation.Sonoporation represents a promising approach to increase targeted drug delivery efficiency by facilitating transport of therapeutic agents to the target tissue with the use of ultrasound. However, most of the current research in sonoporation is performed with external ultrasonic transducers, which hinders the applicability of the therapeutic procedure for treatment of conditions situated deeper into the patient’s body, such as liver or intestinal tumours. This Thesis presents the development process of a miniature-sized 1-3 connectivity piezocomposite 1D phased array for intracorporeal sonoporation. The device was to be incorporated into a capsule or catheter and hence the primary design constraint was the reduced size of the piezoelectric element, which was limited to 2.5 mm in width and 12 mm in length. To meet the needs of the intended application, resonance frequencies of 1.5 MHz and 3.0 MHz were considered. A simulation framework was developed for optimization of the miniature array in relation to the peak negative pressure attained at the focus to mitigate the low power output associated with the limited device dimensions. This was implemented through a multiparametric sweep of the 1-3 piezocomposite geometry-related parameters. Devices made with PZT-5H and PMN-29%PT were evaluated. The optimization algorithm was used to determine specifications for phased array designs based on the two materials and the two resonance frequencies. The 1.5 MHz devices comprised 24 elements and the 3.0 MHz ones had 32 elements. The piezocomposites were manufactured using the dice and fill technique and electroded using a novel method of electrode deposition employing spin coating of Ag ink. Subsequently, the prototype devices were driven with a commercial array controller and characterized with a calibrated needle hydrophone in a scanning tank. Two simulation profiles based on finite element analysis and time extrapolation were developed to model the acoustic beams from the arrays, which were compared and calibrated with experimental data for focal distances between 5 mm and 10 mm and beam steering angles from 0° to 40°. The results showed that modelling could be employed reliably for therapeutic planning. Both the 1.5 MHz and the 3.0 MHz, PZT-5H arrays were tested in vitro and shown to induce and control sonoporation of a human epithelial colorectal adenocarcinoma cell layer. Finally, a 24 element, 1.5 MHz, PZT-5H array was implemented in a 40 mm long by 11 mm diameter tethered, biocompatible capsule intended for in vivo operation. The device was characterized in the scanning tank for steering angles in the range 0° to 56° and focal distances between 4.0 mm and 5.7 mm, and the measured beam profiles were correlated with the simulation framework. The capsule will be tested in future ex-vivo and in-vivo experiments on insulin absorption through porcine small bowel by means of sonoporation
A novel backup protection scheme for hybrid AC/DC power systems
Get PDFThis thesis presents and demonstrates (both via simulation and hardware-based tests) a new protection scheme designed to safeguard hybrid AC/DC distribution networks against DC faults that are not cleared by the main MVDC (Medium Voltage DC) link protection. The protection scheme relies on the apparent impedance measured at the AC "side" of the MVDC link to detect faults on the DC system. It can be readily implemented on existing distance protection relays with no changes to existing measuring equipment. An overview of the literature in this area is presented and it is shown that the protection of MVDC links is only considered at a converter station level. There appears to be no consideration of protecting the MVDC system from the wider AC power system via backup - as would be the case for standard AC distribution network assets, where the failure of main protection would require a (usually remote) backup protection system to operate to clear the fault. Very little literature considers remote backup protection of MVDC links.;To address this issue, the research presented in this thesis characterises the apparent impedance as measured in the neighbouring AC system under various DC fault conditions on an adjacent MVDC link. Initial studies, based on simulations, show that a highly inductive characteristic, in terms of the calculations from the measured AC voltages and currents, is apparent on all three phases in the neighbouring AC system during DC-side pole-to-pole and pole-poleground faults. This response is confirmed via a series of experiments conducted at low voltage in a laboratory environment using scaled down electrical components. From this classification, a fast-acting backup protection methodology, which can detect pole-to-pole and pole-poleground faults within 40 ms, is proposed and trialled through simulation. The solution can be deployed on distance protection relays using a typically unused zone (e.g. zone 4).;New relays could, of course, incorporate this functionality as standard in the future. To maximise confidence and demonstrate the compatibility of the solution, the protection scheme is deployed under a real-time hardware-in-the-loop environment using a commercially available distance protection relay. Suggestions to improve the stability of the proposed solution are discussed and demonstrated. Future areas of work are identified and described. As an appendix, early stage work pertaining to the potential application and benefits of MVDC is presented for two Scottish distribution networks. The findings from this are presented as supplementary material at the end of the thesis.This thesis presents and demonstrates (both via simulation and hardware-based tests) a new protection scheme designed to safeguard hybrid AC/DC distribution networks against DC faults that are not cleared by the main MVDC (Medium Voltage DC) link protection. The protection scheme relies on the apparent impedance measured at the AC "side" of the MVDC link to detect faults on the DC system. It can be readily implemented on existing distance protection relays with no changes to existing measuring equipment. An overview of the literature in this area is presented and it is shown that the protection of MVDC links is only considered at a converter station level. There appears to be no consideration of protecting the MVDC system from the wider AC power system via backup - as would be the case for standard AC distribution network assets, where the failure of main protection would require a (usually remote) backup protection system to operate to clear the fault. Very little literature considers remote backup protection of MVDC links.;To address this issue, the research presented in this thesis characterises the apparent impedance as measured in the neighbouring AC system under various DC fault conditions on an adjacent MVDC link. Initial studies, based on simulations, show that a highly inductive characteristic, in terms of the calculations from the measured AC voltages and currents, is apparent on all three phases in the neighbouring AC system during DC-side pole-to-pole and pole-poleground faults. This response is confirmed via a series of experiments conducted at low voltage in a laboratory environment using scaled down electrical components. From this classification, a fast-acting backup protection methodology, which can detect pole-to-pole and pole-poleground faults within 40 ms, is proposed and trialled through simulation. The solution can be deployed on distance protection relays using a typically unused zone (e.g. zone 4).;New relays could, of course, incorporate this functionality as standard in the future. To maximise confidence and demonstrate the compatibility of the solution, the protection scheme is deployed under a real-time hardware-in-the-loop environment using a commercially available distance protection relay. Suggestions to improve the stability of the proposed solution are discussed and demonstrated. Future areas of work are identified and described. As an appendix, early stage work pertaining to the potential application and benefits of MVDC is presented for two Scottish distribution networks. The findings from this are presented as supplementary material at the end of the thesis
Synthesis of non-natural base-pairs : towards site-specific functionalisation of nucleic acids
No full textAlternative Splicing is one of the most important post-transcriptional processes as it facilitates the formation of multiple protein isoforms from the same gene sequence. Despite alternative splicing being highly regulated, anomalous splicing behaviour can be the root cause of disease states such as cancer. To date, research efforts have looked to explore and understand aspects of the spliceosome machinery but elucidating the effect of changes in the gene sequence upon splicing is significantly lacking. To define this critical effect, improved site-specific labelling of RNA is required.This thesis focuses on the synthesis and development of an orthogonal non-natural base pair system for the purpose of improving current RNA labelling strategies.Chapter one introduces alternative splicing, describes the regulatory processes involved and current methodologies for RNA labelling and their limitations. This chapter also introduces non-natural base pairs as a solution to overcome these limitations as well as other applications for non-natural base pairs. Chapter two describes the development of a library of guanosine analogues using a modular step efficient synthetic approach with the future aim of site specifically labelling viral RNA. Therefore this library was tested for antiviral activity and a trio of purine base analogues were tested for pairing fidelity opposite Hirao’s complimentary base to his purine analogues, the pyrrole analogue Pa by transcription assay. The antiviral testing was promising as no antiviral activity was found, however, the transcription assay did not show improvement over the Pa-s reference standard. Chapter three examines the utility of a new ribose hydroxyl protection strategy with the aim of achieving selective phosphoramidite synthesis of RNA nucleosides to improve the overall yield of non-natural purine phosphoramidites for solid phase RNA synthesis. Synthesis of a non-natural purine phosphoramidite precursor was achieved utilising the chosen strategy.Chapter Four describes the development of a modular synthetic route for 2′-deoxyadenosine phosphoramidite analogues, their incorporation into DNA by solid-phase DNA synthesis and an investigation of their utility for use as DNA aptamers. Incorporation of non-natural phosphoramidites into a 12mer DNA strand was achieved, however, the thermal stability test did not show improved pairing strength opposite Pa compared to the Ds reference standard.Alternative Splicing is one of the most important post-transcriptional processes as it facilitates the formation of multiple protein isoforms from the same gene sequence. Despite alternative splicing being highly regulated, anomalous splicing behaviour can be the root cause of disease states such as cancer. To date, research efforts have looked to explore and understand aspects of the spliceosome machinery but elucidating the effect of changes in the gene sequence upon splicing is significantly lacking. To define this critical effect, improved site-specific labelling of RNA is required.This thesis focuses on the synthesis and development of an orthogonal non-natural base pair system for the purpose of improving current RNA labelling strategies.Chapter one introduces alternative splicing, describes the regulatory processes involved and current methodologies for RNA labelling and their limitations. This chapter also introduces non-natural base pairs as a solution to overcome these limitations as well as other applications for non-natural base pairs. Chapter two describes the development of a library of guanosine analogues using a modular step efficient synthetic approach with the future aim of site specifically labelling viral RNA. Therefore this library was tested for antiviral activity and a trio of purine base analogues were tested for pairing fidelity opposite Hirao’s complimentary base to his purine analogues, the pyrrole analogue Pa by transcription assay. The antiviral testing was promising as no antiviral activity was found, however, the transcription assay did not show improvement over the Pa-s reference standard. Chapter three examines the utility of a new ribose hydroxyl protection strategy with the aim of achieving selective phosphoramidite synthesis of RNA nucleosides to improve the overall yield of non-natural purine phosphoramidites for solid phase RNA synthesis. Synthesis of a non-natural purine phosphoramidite precursor was achieved utilising the chosen strategy.Chapter Four describes the development of a modular synthetic route for 2′-deoxyadenosine phosphoramidite analogues, their incorporation into DNA by solid-phase DNA synthesis and an investigation of their utility for use as DNA aptamers. Incorporation of non-natural phosphoramidites into a 12mer DNA strand was achieved, however, the thermal stability test did not show improved pairing strength opposite Pa compared to the Ds reference standard
SERS-based rapid diagnostics for the detection of biomarkers associated with sepsis
No full textWorldwide, approximately 11 million people lose their lives to sepsis every year, primarily due to the condition being extremely difficult to diagnose. Therefore, early detection of sepsis is crucial for improved patient outcomes and lower mortality rates.;In this investigation, a surface enhanced Raman scattering or SERS-based rapid diagnostic platform was developed for the multiplexed detection of biomarkers associated with sepsis. Two biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6) were detected using a lateral flow immunoassay (LFIA) device combined with SERS-active gold nanoparticles. For CRP, a limit of detection (LOD) of 8 ng/mL was achieved using a portable, handheld Raman spectrometer and these results were comparable to using a benchtop microscope instrument. Additionally, the results showed that SERS was more sensitive than visible RGB analysis. The assay was also capable of semi-quantitative detection of CRP in spiked human plasma samples with a calculated LOD of 5.4 μg/mL using the handheld instrument. CRP concentrations exceeding 10 μg/mL are indicative of a disease state.;A LOD of 10.5 ng/mL was calculated for singleplex IL-6 detection. Multiplex detection of both CRP and IL-6 was also achieved on a single LFIA device using both spatially resolved and signal-resolved SERS analysis. The signal-resolved duplex detection assay, where handheld SERS analysis was performed on a single test region, was capable of quantitative detection of both biomarkers simultaneously and LODs of 7.5 ng/mL and 14.1 ng/mL were calculated for CRP and IL-6 respectively.;Additionally, the optimisation of a 3D microfluidic paper-based diagnostic, or μPAD, device for use with a SERS-based immunoassay was investigated. The flexible design of 3D μPADs offers excellent potential for multiplexing. Quantitative detection of CRP using this rapid diagnostic device was achieved however, the results showed the SERS-based LFIA was superior to the 3D μPAD for detection of CRP and IL-6.;Overall, this work has demonstrated the viability of a SERS-based LFIA rapid diagnostic, combined with a handheld Raman spectrometer, for the portable, multiplexed and fast detection of biomarkers associated with sepsis at the point-of-care.Worldwide, approximately 11 million people lose their lives to sepsis every year, primarily due to the condition being extremely difficult to diagnose. Therefore, early detection of sepsis is crucial for improved patient outcomes and lower mortality rates.;In this investigation, a surface enhanced Raman scattering or SERS-based rapid diagnostic platform was developed for the multiplexed detection of biomarkers associated with sepsis. Two biomarkers, C-reactive protein (CRP) and interleukin-6 (IL-6) were detected using a lateral flow immunoassay (LFIA) device combined with SERS-active gold nanoparticles. For CRP, a limit of detection (LOD) of 8 ng/mL was achieved using a portable, handheld Raman spectrometer and these results were comparable to using a benchtop microscope instrument. Additionally, the results showed that SERS was more sensitive than visible RGB analysis. The assay was also capable of semi-quantitative detection of CRP in spiked human plasma samples with a calculated LOD of 5.4 μg/mL using the handheld instrument. CRP concentrations exceeding 10 μg/mL are indicative of a disease state.;A LOD of 10.5 ng/mL was calculated for singleplex IL-6 detection. Multiplex detection of both CRP and IL-6 was also achieved on a single LFIA device using both spatially resolved and signal-resolved SERS analysis. The signal-resolved duplex detection assay, where handheld SERS analysis was performed on a single test region, was capable of quantitative detection of both biomarkers simultaneously and LODs of 7.5 ng/mL and 14.1 ng/mL were calculated for CRP and IL-6 respectively.;Additionally, the optimisation of a 3D microfluidic paper-based diagnostic, or μPAD, device for use with a SERS-based immunoassay was investigated. The flexible design of 3D μPADs offers excellent potential for multiplexing. Quantitative detection of CRP using this rapid diagnostic device was achieved however, the results showed the SERS-based LFIA was superior to the 3D μPAD for detection of CRP and IL-6.;Overall, this work has demonstrated the viability of a SERS-based LFIA rapid diagnostic, combined with a handheld Raman spectrometer, for the portable, multiplexed and fast detection of biomarkers associated with sepsis at the point-of-care
Establishing the optimal conditions for rotating arm erosion testing, materials characterisation and computational modelling of wind turbine blade rain erosion
No full textThis thesis was previously held under moratorium from 5th August 2020 until 5th August 2022.Leading edge erosion is a growing issue within the wind industry; impacting upon blade performance and efficiency. Even with the wide range of research being conducted, there are currently no apparent foolproof material solutions for the issue. The research presentedhere looks to develop a better understanding of lead edge erosion: firstly through the development and characterisation of an erosion test rig; then by conducting a range of parametric studies, both numerically (finite element) and experimentally, to explore the key factors and damage mechanisms associated with leading edge erosion. This work shows the importance of characterising a test rig before starting any experimental tests, through this work specifically the most optimal operating conditions can be established. Consistent results are key to transferring knowledge from the test rig to real-world applications, and this repeatability can only be reached with proper understanding of the operating conditions and aerodynamics of an erosion test rig. Reliable results were achieved at rotational speeds around 1100 and 1200rpm rather than the fastest rotational speeds, speeds greater than 1200rpm resulted in an increase in droplet breakup and less repeatable results. The development of modelling techniques alongside experimental testing allows for the physics associated with droplet impacts to be fully explored. Sub-surface imagery, through XCT scans, showed that any defects near the surface of a sample can lead to stress concentrations at the damaged area. The XCT imagery also showed that voids near the composite interface did not affect the erosion initiation or location. Subsequent modelling work also revealed that stress concentrations were the main differing factor between undamaged and damaged samples undergoing erosion, rather than a change in the peak stresses. The peak compressive and shear stresses remained similar regardless of the state of the sample, however, the stress waves became concentrated centrally, around the damaged area, once erosion had initiated. An investigation of a variety of different samples showed that currently industry struggles to find a balance between performance and consistency. Mass loss curves were established for each of the different materials tested, with the affect of number of impacts and kinetic energy also explored. Different failure mechanisms were observed: delamination causing severe damage and brittle failure most common amongst samples. Interesting work is being undertaken where coatings are optimised for certain operating conditions; showing that there is an understanding of the failure mechanisms present, though the level of understanding has not reached the stage where a significant improvement in blade lifetime can be achieved. Future work and research development aimed at further understanding the issues of blade leading edge erosion are also identified, discussed and recommendations given.Leading edge erosion is a growing issue within the wind industry; impacting upon blade performance and efficiency. Even with the wide range of research being conducted, there are currently no apparent foolproof material solutions for the issue. The research presentedhere looks to develop a better understanding of lead edge erosion: firstly through the development and characterisation of an erosion test rig; then by conducting a range of parametric studies, both numerically (finite element) and experimentally, to explore the key factors and damage mechanisms associated with leading edge erosion. This work shows the importance of characterising a test rig before starting any experimental tests, through this work specifically the most optimal operating conditions can be established. Consistent results are key to transferring knowledge from the test rig to real-world applications, and this repeatability can only be reached with proper understanding of the operating conditions and aerodynamics of an erosion test rig. Reliable results were achieved at rotational speeds around 1100 and 1200rpm rather than the fastest rotational speeds, speeds greater than 1200rpm resulted in an increase in droplet breakup and less repeatable results. The development of modelling techniques alongside experimental testing allows for the physics associated with droplet impacts to be fully explored. Sub-surface imagery, through XCT scans, showed that any defects near the surface of a sample can lead to stress concentrations at the damaged area. The XCT imagery also showed that voids near the composite interface did not affect the erosion initiation or location. Subsequent modelling work also revealed that stress concentrations were the main differing factor between undamaged and damaged samples undergoing erosion, rather than a change in the peak stresses. The peak compressive and shear stresses remained similar regardless of the state of the sample, however, the stress waves became concentrated centrally, around the damaged area, once erosion had initiated. An investigation of a variety of different samples showed that currently industry struggles to find a balance between performance and consistency. Mass loss curves were established for each of the different materials tested, with the affect of number of impacts and kinetic energy also explored. Different failure mechanisms were observed: delamination causing severe damage and brittle failure most common amongst samples. Interesting work is being undertaken where coatings are optimised for certain operating conditions; showing that there is an understanding of the failure mechanisms present, though the level of understanding has not reached the stage where a significant improvement in blade lifetime can be achieved. Future work and research development aimed at further understanding the issues of blade leading edge erosion are also identified, discussed and recommendations given
A framework to support the implementation of Product Lifecycle Management (PLM) on Engineer to Order (ETO) products
Get PDFPreviously held under moratorium from 1st September 2020 until 2nd September 2024.This thesis presents the first ever framework for implementing Product Lifecycle Management (PLM) within high value Engineering to Order (ETO) programmes. It describes the PLM related challenges in large-scale, complex, long-life, no prototype, highly customised, one-off or few of kind ETO products compared to other product types such as Make to Stock (MTS), Make to Order (MTO) or Assemble to Order (ATO). It highlights that the scale, complexity, uncertainty, long-lifecycle, maturity management and an inability to prototype ETO products results in significant challenges necessitating a tailored approach to PLM Implementation.
The framework has been developed using a qualitative methodology based on the thematic analysis of 27 semi-structured interviews, and 1 pilot interview. The participants were senior personnel from 11 ETO organisations in the UK, France, Australia, USA and Canada.
Each of the themes in the framework is described in information, process, people and technology subsections within the main section of objectives, challenges and enablers. The themes were developed using a qualitative methodology which enabled the grouping of interview responses allowing the related key points from the interviews to be described. To provide an audit trail to support the truthfulness of the findings, each key point was referenced to the transcribed responses. The results of this preparation supported the development of the findings as each theme and related key points could be easily identified and described.
The validation and evaluation used a questionnaire to ask selected participants from ETO products for their opinion on statements related to the framework. There were 19 evaluation participants who were selected from 7 ETO organisations. The responses to the questionnaire statements and the comments supported the objectives of the questionnaire for quality, structure and versatility with the majority (95%) of the responses either agreeing or strongly agreeing with the statements.This thesis presents the first ever framework for implementing Product Lifecycle Management (PLM) within high value Engineering to Order (ETO) programmes. It describes the PLM related challenges in large-scale, complex, long-life, no prototype, highly customised, one-off or few of kind ETO products compared to other product types such as Make to Stock (MTS), Make to Order (MTO) or Assemble to Order (ATO). It highlights that the scale, complexity, uncertainty, long-lifecycle, maturity management and an inability to prototype ETO products results in significant challenges necessitating a tailored approach to PLM Implementation.
The framework has been developed using a qualitative methodology based on the thematic analysis of 27 semi-structured interviews, and 1 pilot interview. The participants were senior personnel from 11 ETO organisations in the UK, France, Australia, USA and Canada.
Each of the themes in the framework is described in information, process, people and technology subsections within the main section of objectives, challenges and enablers. The themes were developed using a qualitative methodology which enabled the grouping of interview responses allowing the related key points from the interviews to be described. To provide an audit trail to support the truthfulness of the findings, each key point was referenced to the transcribed responses. The results of this preparation supported the development of the findings as each theme and related key points could be easily identified and described.
The validation and evaluation used a questionnaire to ask selected participants from ETO products for their opinion on statements related to the framework. There were 19 evaluation participants who were selected from 7 ETO organisations. The responses to the questionnaire statements and the comments supported the objectives of the questionnaire for quality, structure and versatility with the majority (95%) of the responses either agreeing or strongly agreeing with the statements
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