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Fractional derivative models for the spread of diseases
Get PDFThis thesis considers the mathematical modelling of disease, using fractional differential equations in order to provide a tool for the description of memory effects. In Chapter 3 we illustrate a commensurate fractional order tumor model, and we find a critical value of the fractional derivative dependent on the parameter values of the model. For fractional derivatives of orders less than the critical value an unstable equilibrium point of the system becomes stable. In order to show changes in the observed areas of attraction of two stable points in the system, we then consider a fractional order SIR epidemic model and investigate the change from a monostable to a bistable system.;Chapter 4 considers a model for virus dynamics where the fractional orders for populations are different, called an incommensurate system. An approximate analytical solution for the characteristic equation of the incommensurate model is found when the different fractional orders are similar and close to the critical value of the fractional order of the commensurate system. In addition, the instability boundary is found as a function of both parameters. A comparison between analytical and numerical results shows the high accuracy of this approximation.;Chapter 5 consists of two parts, in the first part we generalise the integer Fisher's equation to be a space-time fractional differential equation and consider travelling wave solutions. In the second part we generalise an integer SIR model with spatial heterogeneity, which was studied by Murray [117], to a space-time fractional derivative model. We apply the (G0/G)-expansion method and find travelling wave solutions, although in this case we must consider the Jumarie's modified Riemann-Liouville fractional derivative. Finally, we consider the effect of changing the orders of time and space fractional derivatives on the location and speed of the travelling wave solution.This thesis considers the mathematical modelling of disease, using fractional differential equations in order to provide a tool for the description of memory effects. In Chapter 3 we illustrate a commensurate fractional order tumor model, and we find a critical value of the fractional derivative dependent on the parameter values of the model. For fractional derivatives of orders less than the critical value an unstable equilibrium point of the system becomes stable. In order to show changes in the observed areas of attraction of two stable points in the system, we then consider a fractional order SIR epidemic model and investigate the change from a monostable to a bistable system.;Chapter 4 considers a model for virus dynamics where the fractional orders for populations are different, called an incommensurate system. An approximate analytical solution for the characteristic equation of the incommensurate model is found when the different fractional orders are similar and close to the critical value of the fractional order of the commensurate system. In addition, the instability boundary is found as a function of both parameters. A comparison between analytical and numerical results shows the high accuracy of this approximation.;Chapter 5 consists of two parts, in the first part we generalise the integer Fisher's equation to be a space-time fractional differential equation and consider travelling wave solutions. In the second part we generalise an integer SIR model with spatial heterogeneity, which was studied by Murray [117], to a space-time fractional derivative model. We apply the (G0/G)-expansion method and find travelling wave solutions, although in this case we must consider the Jumarie's modified Riemann-Liouville fractional derivative. Finally, we consider the effect of changing the orders of time and space fractional derivatives on the location and speed of the travelling wave solution
User-based gesture vocabulary for form creation during a product design process
Get PDFThere are inconsistencies between the nature of the conceptual design and the functionalities of the computational systems supporting it, which disrupt the designers’ process, focusing on technology rather than designers’ needs. A need for elicitation of hand gestures appropriate for the requirements of the conceptual design, rather than those arbitrarily chosen or focusing on ease of implementation was identified.The aim of this thesis is to identify natural and intuitive hand gestures for conceptual design, performed by designers (3rd, 4th year product design engineering students and recent graduates) working on their own, without instruction and without limitations imposed by the facilitating technology. This was done via a user centred study including 44 participants. 1785 gestures were collected. Gestures were explored as a sole mean for shape creation and manipulation in virtual 3D space. Gestures were identified, described in writing, sketched, coded based on the taxonomy used, categorised based on hand form and the path travelled and variants identified. Then they were statistically analysed to ascertain agreement rates between the participants, significance of the agreement and the likelihood of number of repetitions for each category occurring by chance. The most frequently used and statistically significant gestures formed the consensus set of vocabulary for conceptual design. The effect of the shape of the manipulated object on the gesture performed, and if the sequence of the gestures participants proposed was different from the established CAD solid modelling practices were also observed.Vocabulary was evaluated by non-designer participants, and the outcomes have shown that the majority of gestures were appropriate and easy to perform. Evaluation was performed theoretically and in the VR environment. Participants selected their preferred gestures for each activity, and a variant of the vocabulary for conceptual design was created as an outcome, that aims to ensure that extensive training is not required, extending the ability to design beyond trained designers only.There are inconsistencies between the nature of the conceptual design and the functionalities of the computational systems supporting it, which disrupt the designers’ process, focusing on technology rather than designers’ needs. A need for elicitation of hand gestures appropriate for the requirements of the conceptual design, rather than those arbitrarily chosen or focusing on ease of implementation was identified.The aim of this thesis is to identify natural and intuitive hand gestures for conceptual design, performed by designers (3rd, 4th year product design engineering students and recent graduates) working on their own, without instruction and without limitations imposed by the facilitating technology. This was done via a user centred study including 44 participants. 1785 gestures were collected. Gestures were explored as a sole mean for shape creation and manipulation in virtual 3D space. Gestures were identified, described in writing, sketched, coded based on the taxonomy used, categorised based on hand form and the path travelled and variants identified. Then they were statistically analysed to ascertain agreement rates between the participants, significance of the agreement and the likelihood of number of repetitions for each category occurring by chance. The most frequently used and statistically significant gestures formed the consensus set of vocabulary for conceptual design. The effect of the shape of the manipulated object on the gesture performed, and if the sequence of the gestures participants proposed was different from the established CAD solid modelling practices were also observed.Vocabulary was evaluated by non-designer participants, and the outcomes have shown that the majority of gestures were appropriate and easy to perform. Evaluation was performed theoretically and in the VR environment. Participants selected their preferred gestures for each activity, and a variant of the vocabulary for conceptual design was created as an outcome, that aims to ensure that extensive training is not required, extending the ability to design beyond trained designers only
Dynamics in entrepreneurial decision-making and coping strategies, diary-based case analysis of resilience in early stage entrepreneurs as a developmental process
Get PDFEntrepreneurship scholars have highlighted the need to specify entrepreneurial performance dynamics. While a growing chorus of scholars have highlighted the developmental nature of the entrepreneurial process, details of how this process develops still need empirical elaboration. The thesis explores the role of entrepreneurs’ decision-making and coping strategies as an emerging temporal experience. This thesis asks how capacities are developed by entrepreneurs to adapt and overcome adversity during venture creation. This research contributes much needed empirical elaboration to how entrepreneurial decision-making plays out through deliberation on factors relating to adversity facing their businesses. The study adduced longitudinal evidence from 108 diary-based accounts of participants’ day-to-day experience and 12 in-depth qualitative interviews offering direct insight into the entrepreneurial process, drawn from six participating entrepreneurs over a three-month timeframe. The research adopted philosophical, epistemological and methodological rationales conducive to a dynamic and process-focused approach. This research employed a ‘connected contributions’ approach for conducting mixed methods research, which aimed for complementary assistance by combining the strengths from both qualitative (core) and quantitative (supplementary) methods. Within- and cross-case analysis reveal patterns for how unfolding business challenges were perceived and what resources were used to cope with chronic and acute challenges. These patterns were grouped under the categories of perceptions of external business context, entrepreneurial self-efficacy, and entrepreneurial effectuation. The thesis focuses on the micro-processual dynamics of decision-making and coping strategies with the aim of making conceptual contributions to the literature on entrepreneurial resilience. It also focuses on within-person drivers for continuity and change in entrepreneurial performance, with emphasis on links to subsequent failure experiences, learning and adaptation to adversity. Findings indicate that entrepreneurs developed decision biases, stress responses and coping strategies to reduce uncertainty within their businesses, regardless of emergent experiences with emotional, financial and relational impacts. Implications for entrepreneurs, pedagogy and future research are discussed, as well as the limitations of the thesis and avenues for further research.Entrepreneurship scholars have highlighted the need to specify entrepreneurial performance dynamics. While a growing chorus of scholars have highlighted the developmental nature of the entrepreneurial process, details of how this process develops still need empirical elaboration. The thesis explores the role of entrepreneurs’ decision-making and coping strategies as an emerging temporal experience. This thesis asks how capacities are developed by entrepreneurs to adapt and overcome adversity during venture creation. This research contributes much needed empirical elaboration to how entrepreneurial decision-making plays out through deliberation on factors relating to adversity facing their businesses. The study adduced longitudinal evidence from 108 diary-based accounts of participants’ day-to-day experience and 12 in-depth qualitative interviews offering direct insight into the entrepreneurial process, drawn from six participating entrepreneurs over a three-month timeframe. The research adopted philosophical, epistemological and methodological rationales conducive to a dynamic and process-focused approach. This research employed a ‘connected contributions’ approach for conducting mixed methods research, which aimed for complementary assistance by combining the strengths from both qualitative (core) and quantitative (supplementary) methods. Within- and cross-case analysis reveal patterns for how unfolding business challenges were perceived and what resources were used to cope with chronic and acute challenges. These patterns were grouped under the categories of perceptions of external business context, entrepreneurial self-efficacy, and entrepreneurial effectuation. The thesis focuses on the micro-processual dynamics of decision-making and coping strategies with the aim of making conceptual contributions to the literature on entrepreneurial resilience. It also focuses on within-person drivers for continuity and change in entrepreneurial performance, with emphasis on links to subsequent failure experiences, learning and adaptation to adversity. Findings indicate that entrepreneurs developed decision biases, stress responses and coping strategies to reduce uncertainty within their businesses, regardless of emergent experiences with emotional, financial and relational impacts. Implications for entrepreneurs, pedagogy and future research are discussed, as well as the limitations of the thesis and avenues for further research
Chemical profiling and biotechnological potential of marine microalgae in response to light and abiotic stress
Get PDFMicroalgae form the base of the aquatic food chain and have important ecological functions, including nutrient cycling and carbon capturing. These microscopic eukaryotes are incredibly diverse, with an estimated 72,000 extant species. They have been investigated for their biotechnological potential in industries such as nutraceutical, cosmetic, and biofuel. Most research has focused on specific high-value metabolites such as astaxanthin or β-carotene for human health, or classes of natural products such as polyunsaturated fatty acids for biofuels. However, a systematicuntargeted approach to exploring the chemical diversity of microalgal metabolites has yet to be performed. Unlocking this chemical potential could provide further applications and incentives to the microalgal biotechnology sector.This thesis aims to fill this gap by exploring the chemical space of microalgae and the elicitation of further chemistry using abiotic stress. A comparative metabolomics study of 36 microalgal strains from both freshwater and marine environments showed that Haptophytes were a rich source of chemistry compared to the well-studied Chlorophytes. It also explored chemical diversity across strains of the same species, providing evidence that isolation environment rather than phylogenetic relationships could be used to group microalgae based on chemical profiles. To investigate thechemistry produced by three strains of marine microalgae, Dunaliella primolecta, Nannochloropsis oculata, and Phaeodactylum tricornutum were cultured under varying conditions of salinity, sodium chloride, nitrate, and pH and Global Natural Products Social (GNPS) molecular networking was used to gain insights into the effect of these stresses on metabolite production. A total of 2284 metabolites were detected across all strains and conditions, with 49% of those metabolites specific to cultures grown under stress conditions (i.e., not in the control). Salinity had the greatest effectwith 22.8% of metabolites only produced under salinity stress. From comparison with over 33 libraries of mass spectral data, only five metabolites were identified, stressing the need for more open-access natural product -and specifically algal natural product - databases. Finally, we partnered with Xanthella Ltd., a marine biotechnology company in Scotland, to study the effect of 405 nm light on growth of four strains of microalgae and the production of antimicrobial metabolites. This wavelength has been shown to reduce bacterial contamination in cultures but is an expensive regimen to apply at a large scale. The production of high-value metabolites under this light regimen could enable culturing under 405 nm illumination to be economically viable. Although no bioactivity was observed from extracts or fractions, molecular networking did show that 16-25% of metabolites were either exclusively produced under 405 nm illumination or absent from the white light control condition. This thesis offers a starting point for fundamental and comparative research into microalgal growth and metabolite production and their applications in human health.Microalgae form the base of the aquatic food chain and have important ecological functions, including nutrient cycling and carbon capturing. These microscopic eukaryotes are incredibly diverse, with an estimated 72,000 extant species. They have been investigated for their biotechnological potential in industries such as nutraceutical, cosmetic, and biofuel. Most research has focused on specific high-value metabolites such as astaxanthin or β-carotene for human health, or classes of natural products such as polyunsaturated fatty acids for biofuels. However, a systematicuntargeted approach to exploring the chemical diversity of microalgal metabolites has yet to be performed. Unlocking this chemical potential could provide further applications and incentives to the microalgal biotechnology sector.This thesis aims to fill this gap by exploring the chemical space of microalgae and the elicitation of further chemistry using abiotic stress. A comparative metabolomics study of 36 microalgal strains from both freshwater and marine environments showed that Haptophytes were a rich source of chemistry compared to the well-studied Chlorophytes. It also explored chemical diversity across strains of the same species, providing evidence that isolation environment rather than phylogenetic relationships could be used to group microalgae based on chemical profiles. To investigate thechemistry produced by three strains of marine microalgae, Dunaliella primolecta, Nannochloropsis oculata, and Phaeodactylum tricornutum were cultured under varying conditions of salinity, sodium chloride, nitrate, and pH and Global Natural Products Social (GNPS) molecular networking was used to gain insights into the effect of these stresses on metabolite production. A total of 2284 metabolites were detected across all strains and conditions, with 49% of those metabolites specific to cultures grown under stress conditions (i.e., not in the control). Salinity had the greatest effectwith 22.8% of metabolites only produced under salinity stress. From comparison with over 33 libraries of mass spectral data, only five metabolites were identified, stressing the need for more open-access natural product -and specifically algal natural product - databases. Finally, we partnered with Xanthella Ltd., a marine biotechnology company in Scotland, to study the effect of 405 nm light on growth of four strains of microalgae and the production of antimicrobial metabolites. This wavelength has been shown to reduce bacterial contamination in cultures but is an expensive regimen to apply at a large scale. The production of high-value metabolites under this light regimen could enable culturing under 405 nm illumination to be economically viable. Although no bioactivity was observed from extracts or fractions, molecular networking did show that 16-25% of metabolites were either exclusively produced under 405 nm illumination or absent from the white light control condition. This thesis offers a starting point for fundamental and comparative research into microalgal growth and metabolite production and their applications in human health
Investigation of key challenges facing aerogel composites development through multiscale approach
Get PDFThe aerogel particulate and fibre reinforced composites are becoming more and more popular due to their exceptional properties, nevertheless, they do face a range of challenges that need to be overcome for wider applications. The main ones include a lack of understanding of the interactions between aerogels and reinforcing fibre materials, lack of appropriate models to predict their performance, and finally, lack of property database, allowing for an informative selection of aerogel composites as a viable alternative to other materials. The primary goal of this work is to tackle those challenges and provide a better fundamental understanding of some cases of aerogel composites.In order to fulfil the thesis' goals, the aerogel influence on the various thermal and mechanical properties of epoxy and vinyl ester polymers were investigated. By incorporating various weight contents and sizes of silica and polyimide aerogel particles into these polymers, their thermal conductivity, compressive properties, and other thermomechanical properties in these particle-filled polymers have been evaluated. Overall, created composites presented a significant decrease in thermal conductivity, while the introduction of porous particles deteriorated composite mechanical response. Additionally, micromechanical testing of the interface between aerogel and fibre reinforcement has been performed for the first time to understand their bonding ability. By designing a method to deposit an aerogel droplet surrounding the fibre, the microbond tests were enabled, and the results revealed poor adhesion between aerogel and selected fibre type in general.In addition to the experimental part, this study also focused on modelling aerogels and aerogel composites, which provided insight into the interactions between aerogels and most common reinforcement materials using a multiscale approach. As a result, the nanoscale analysis using molecular dynamics allowed to estimate thermal and mechanical properties of low density silica and polyimide. What is more, the aerogel-fibre interfacial properties values have also been obtained though modelling. Finally, the microscale model was used to model the thermal and mechanical properties of epoxy composites. A close match between experimental and modelled thermal conductivity and compressive modulus of epoxy combined with low density silica or polyimide particles has been achieved by incorporating the nanoscale properties into the micromechanical model.The aerogel particulate and fibre reinforced composites are becoming more and more popular due to their exceptional properties, nevertheless, they do face a range of challenges that need to be overcome for wider applications. The main ones include a lack of understanding of the interactions between aerogels and reinforcing fibre materials, lack of appropriate models to predict their performance, and finally, lack of property database, allowing for an informative selection of aerogel composites as a viable alternative to other materials. The primary goal of this work is to tackle those challenges and provide a better fundamental understanding of some cases of aerogel composites.In order to fulfil the thesis' goals, the aerogel influence on the various thermal and mechanical properties of epoxy and vinyl ester polymers were investigated. By incorporating various weight contents and sizes of silica and polyimide aerogel particles into these polymers, their thermal conductivity, compressive properties, and other thermomechanical properties in these particle-filled polymers have been evaluated. Overall, created composites presented a significant decrease in thermal conductivity, while the introduction of porous particles deteriorated composite mechanical response. Additionally, micromechanical testing of the interface between aerogel and fibre reinforcement has been performed for the first time to understand their bonding ability. By designing a method to deposit an aerogel droplet surrounding the fibre, the microbond tests were enabled, and the results revealed poor adhesion between aerogel and selected fibre type in general.In addition to the experimental part, this study also focused on modelling aerogels and aerogel composites, which provided insight into the interactions between aerogels and most common reinforcement materials using a multiscale approach. As a result, the nanoscale analysis using molecular dynamics allowed to estimate thermal and mechanical properties of low density silica and polyimide. What is more, the aerogel-fibre interfacial properties values have also been obtained though modelling. Finally, the microscale model was used to model the thermal and mechanical properties of epoxy composites. A close match between experimental and modelled thermal conductivity and compressive modulus of epoxy combined with low density silica or polyimide particles has been achieved by incorporating the nanoscale properties into the micromechanical model
Novel development of eco-friendly porous thermal insulation materials and the application
Get PDFPreviously held under moratorium from 12th April 2022 until 12th April 2024.Inorganic thermal insulation materials, such as porous geopolymer and aerogel, have receivedunprecedented attention due to their excellent thermal insulation performance and non-burningcharacteristics. They are also more environmentally friendly compared to conventionalsynthetic insulation materials. The environmental benefit could be further enlarged whenrecycled glass fibre (rGF) is introduced in the geopolymer and aerogel system.Waste glass has been investigated extensively in the geopolymer system. However, the effectof recycled glass fibre on the thermal property of geopolymer is not commonly mentioned. Inthis thesis, the effect of rGF content on the mechanical and thermal properties of geopolymerwas examined. Results indicated that the addition of rGF in geopolymer significantly increasedthe compressive strength (92 to 165 kPa) without diminishing the thermal performance (51.1to 54.6 mW/m.K). In addition, a considerable amount of recycled glass fibres (25 g for threespecimens) was reused. This paves a promising way to maximise environmental benefits andshows great potential in the thermal insulation field.Another avenue of research in this thesis was assessing the feasibility of fabricating short rGFmats and incorporating the prepared rGF mats with aerogel since these are rarely reported. Inthis thesis, rGF was used to fabricate the glass fibre mat via wet deposition and chemicalbonding process to support the aerogel network. The mechanical and thermal performance ofthe rGF-aerogel composites was then characterised. The successfully prepared rGF matprovides a valuable reference for the preparation of recycled short fibre mats. The preparedrGF-aerogel had a low thermal conductivity (23.8 mW/m.K). Although the thermalconductivity of the rGF-aerogel is slightly higher than the prepared aerogel reinforced withthe commercial GF mat (18.3 mW/m.K), it still paves a promising way to maximiseenvironmental benefits and shows great potential in the thermal insulation field.The potential application of aerogel composites in packaging was also explored since it israrely reported. In this thesis, an optimised mathematical model was derived by incorporatingtwo mathematical models described in the literature to improve the accuracy of the calculatedresults. A number of experiments were then set up to validate the optimised model. The resultsshowed that the insulating performance of packages insulated with aerogel composites wassignificantly improved (2 times better than expanded polystyrene). This finding suggests thataerogel composites have a great potential to satisfy the requirement of temperature control forlong-haul transportation of fresh goods. The optimised model can be utilised as a cost-effectivetool for packaging design concerning passive temperature control with improved accuracy.Inorganic thermal insulation materials, such as porous geopolymer and aerogel, have receivedunprecedented attention due to their excellent thermal insulation performance and non-burningcharacteristics. They are also more environmentally friendly compared to conventionalsynthetic insulation materials. The environmental benefit could be further enlarged whenrecycled glass fibre (rGF) is introduced in the geopolymer and aerogel system.Waste glass has been investigated extensively in the geopolymer system. However, the effectof recycled glass fibre on the thermal property of geopolymer is not commonly mentioned. Inthis thesis, the effect of rGF content on the mechanical and thermal properties of geopolymerwas examined. Results indicated that the addition of rGF in geopolymer significantly increasedthe compressive strength (92 to 165 kPa) without diminishing the thermal performance (51.1to 54.6 mW/m.K). In addition, a considerable amount of recycled glass fibres (25 g for threespecimens) was reused. This paves a promising way to maximise environmental benefits andshows great potential in the thermal insulation field.Another avenue of research in this thesis was assessing the feasibility of fabricating short rGFmats and incorporating the prepared rGF mats with aerogel since these are rarely reported. Inthis thesis, rGF was used to fabricate the glass fibre mat via wet deposition and chemicalbonding process to support the aerogel network. The mechanical and thermal performance ofthe rGF-aerogel composites was then characterised. The successfully prepared rGF matprovides a valuable reference for the preparation of recycled short fibre mats. The preparedrGF-aerogel had a low thermal conductivity (23.8 mW/m.K). Although the thermalconductivity of the rGF-aerogel is slightly higher than the prepared aerogel reinforced withthe commercial GF mat (18.3 mW/m.K), it still paves a promising way to maximiseenvironmental benefits and shows great potential in the thermal insulation field.The potential application of aerogel composites in packaging was also explored since it israrely reported. In this thesis, an optimised mathematical model was derived by incorporatingtwo mathematical models described in the literature to improve the accuracy of the calculatedresults. A number of experiments were then set up to validate the optimised model. The resultsshowed that the insulating performance of packages insulated with aerogel composites wassignificantly improved (2 times better than expanded polystyrene). This finding suggests thataerogel composites have a great potential to satisfy the requirement of temperature control forlong-haul transportation of fresh goods. The optimised model can be utilised as a cost-effectivetool for packaging design concerning passive temperature control with improved accuracy
Supramolecular amorphous systems : analysis and control of non-crystalline pharmaceutical systems
Get PDFThis thesis was previously held under moratorium from 12th May 2022 until 12th May 2025.Recent years have seen an increase in interest in amorphous pharmaceutical solids due to their solubility benefits when compared to their crystalline counterparts. This thesis reports approaches for reliable collection and analysis of X-ray pair distribution function (PDF) data to enable structural insights to amorphous pharmaceuticals to improve understanding of structure and properties in these systems. A number of factors are considered and assessed for enabling high-quality laboratory PDF, including sample handling and data collection methodologies, before applying to the amorphous systems indomethacin-polyvinylpyrrolidone (IND-PVP) and AZD5718, a small-molecule active pharmaceutical ingredient (API) currently under development at Astra Zeneca. High-throughput synchrotron X-ray PDF is applied to amorphous paracetamol (PCM) to understand structure and transformations in the amorphous solid. Optimisation of data collection, sample handling and data treatment procedures enabled laboratory PDF analysis of amorphous pharmaceuticals which compared favourably to benchmark synchrotron PDFs. This enabled in-house structural investigations including limit of detection of crystallinity and the impact of elevated humidity on the amorphous structure. PDF was found to be sensitive to both low levels of crystalline material and structural changes induced by moisture absorption. Investigations of amorphous AZD5718 revealed subtle structural changes as a result of preparation method, which were largely due to small differences in the water content in the two preparations, demonstrating again the sensitivity of PDF analysis to subtle structural changes. MD simulations revealed significant disruption of hydrogen bonds in the amorphous matrix by water. By extracting sample conformations from the MD simulations, the dominance of the intramolecular structure to features in the low- region of the PDF was demonstrated.
High-throughput synchrotron PDF analysis enabled tracking of structural transformations in amorphous PCM, where subtle differences were detected statistically through the - and glass transitions, and upon crystallisation. MD simulations coupled with PDF allowed production of a structural model of amorphous PCM, and provided a possible explanation for the observed crystallisation behaviour of amorphous PCM.Recent years have seen an increase in interest in amorphous pharmaceutical solids due to their solubility benefits when compared to their crystalline counterparts. This thesis reports approaches for reliable collection and analysis of X-ray pair distribution function (PDF) data to enable structural insights to amorphous pharmaceuticals to improve understanding of structure and properties in these systems. A number of factors are considered and assessed for enabling high-quality laboratory PDF, including sample handling and data collection methodologies, before applying to the amorphous systems indomethacin-polyvinylpyrrolidone (IND-PVP) and AZD5718, a small-molecule active pharmaceutical ingredient (API) currently under development at Astra Zeneca. High-throughput synchrotron X-ray PDF is applied to amorphous paracetamol (PCM) to understand structure and transformations in the amorphous solid. Optimisation of data collection, sample handling and data treatment procedures enabled laboratory PDF analysis of amorphous pharmaceuticals which compared favourably to benchmark synchrotron PDFs. This enabled in-house structural investigations including limit of detection of crystallinity and the impact of elevated humidity on the amorphous structure. PDF was found to be sensitive to both low levels of crystalline material and structural changes induced by moisture absorption. Investigations of amorphous AZD5718 revealed subtle structural changes as a result of preparation method, which were largely due to small differences in the water content in the two preparations, demonstrating again the sensitivity of PDF analysis to subtle structural changes. MD simulations revealed significant disruption of hydrogen bonds in the amorphous matrix by water. By extracting sample conformations from the MD simulations, the dominance of the intramolecular structure to features in the low- region of the PDF was demonstrated.
High-throughput synchrotron PDF analysis enabled tracking of structural transformations in amorphous PCM, where subtle differences were detected statistically through the - and glass transitions, and upon crystallisation. MD simulations coupled with PDF allowed production of a structural model of amorphous PCM, and provided a possible explanation for the observed crystallisation behaviour of amorphous PCM
Legal place-making in Europe's seas : laying the foundations for a human rights-based approach to maritime spatial planning in the EU
Get PDFPreviously held under moratorium from 02/06/2023 until 02/06/2025
Understanding the nature and experiences of work and employment within the context of public sector reforms in professional work
Get PDFThe thesis provides a broad examination of the dynamics of public sectorreform under austerity and working conditions in the context of professionalvalues. A multilevel framework for understanding influences on, and dynamics in, professional experiences of work and employment in public service subject to neoliberal reform is proposed. Social influences, namely professional values and identities, are seen as central to understanding evaluations of job characteristics within this context. The framework accounts for the particular nature of employment relations in public service which are characterised by tensions in the competing interests of the neoliberal state as employer/reformer and the professions working within them as well as their representation by trade unions. Across two empirical case studies in the Scottish context, namely Further Education colleges and Fire and Rescue Services, drawing on qualitative methods, the following are explored: (1) macro-level reform and the connected fiscal policy context in which public sector work and employment are embedded; (2) profession-level influences (professional values as encapsulated in shared identities); (3) two sets of working conditions relating to characteristics of work and employment; and (4) individual experiences of this interdynamic of influences. This has supported a reconceptualisation of the social dimensions of work, and in particular of additional sources of intensity in work, which in this research were revealed through the lens of professional values. The multidimensional nature of social characteristics of professional jobs in public service, including the importance of prosocial job characteristics within this context, is emphasised.The thesis provides a broad examination of the dynamics of public sectorreform under austerity and working conditions in the context of professionalvalues. A multilevel framework for understanding influences on, and dynamics in, professional experiences of work and employment in public service subject to neoliberal reform is proposed. Social influences, namely professional values and identities, are seen as central to understanding evaluations of job characteristics within this context. The framework accounts for the particular nature of employment relations in public service which are characterised by tensions in the competing interests of the neoliberal state as employer/reformer and the professions working within them as well as their representation by trade unions. Across two empirical case studies in the Scottish context, namely Further Education colleges and Fire and Rescue Services, drawing on qualitative methods, the following are explored: (1) macro-level reform and the connected fiscal policy context in which public sector work and employment are embedded; (2) profession-level influences (professional values as encapsulated in shared identities); (3) two sets of working conditions relating to characteristics of work and employment; and (4) individual experiences of this interdynamic of influences. This has supported a reconceptualisation of the social dimensions of work, and in particular of additional sources of intensity in work, which in this research were revealed through the lens of professional values. The multidimensional nature of social characteristics of professional jobs in public service, including the importance of prosocial job characteristics within this context, is emphasised
Optical sectioning techniques for widefield fluorescence mesoscopy with the Mesolens
Get PDFOptical sectioning in fluorescence microscopy is the process of removing out-of-focus light from the final image. Several techniques have been developed over the years and the gold standard remains confocal laser scanning microscopy (CLSM). As a point scanning instrument, a confocal microscope acquires data one pixel at a time which results in long acquisition times for large field of view (FOV), high-resolution images. Moreover, the confocal method is not useful when imaging large volume specimens with a low power, low numerical aperture (NA) lens. Hence optical sectioning techniques for widefield fluorescence imaging which use a digital camera to rapidly acquire high-resolution images are highly sought after. Widefield detection requires much less excitation light intensity allowing gentler imaging with less photobleaching and phototoxic effects simultaneously outperforming CLSM in acquisition speed.
This thesis reports the development of optical sectioning imaging modalities that have been specified to be compatible with the unique properties of the Mesolens, a novel microscope objective lens that combines millimetre scale FOV, submicron lateral resolution and a long working distance. Firstly, HiLo microscopy was adapted into HiLo mesoscopy. HiLo mesoscopy performs optical sectioning by modulating the in-focus signal with random speckle illumination while leaving out of focus signal uniform. Thus, a weighted map of the image is created that holds information of where the image is in focus and where it is out of focus. HiLo mesoscopy achieved a section thickness of 5.2±0.3 μm at an acquisition speed of 30 seconds per image pair with an additional post-processing time of ~5 minutes compared to CLSM with a section thickness of approximately 6 μm and an acquisition speed of 15 minutes for a three-frame-average final image. Next, a Gaussian light sheet illuminator was constructed using a cylindrical lens to form a light sheet that covered the field of view of the Mesolens. Although the optical section thickness was 30 μm at the center and 40 μm at the edge of the Mesolens FOV, ten times larger than the axial resolution of 7 μm of the Mesolens would require for light sheet microscopy, in optically cleared and thick specimens the out-of-focus background was reduced when compared to widefield illumination when using this simple setup. Compared to CLSM, the section capability of the Gaussian light sheet was inferior, however, the acquisition speed is only limited by the camera framerate and the photodose to the specimen was low, as can be expected from a light sheet illumination setup.
Lastly, a structured illumination microscopy (SIM) technique called blind-SIM was implemented to attempt super-resolution (SR) at the mesoscale. Blind-SIM uses random speckle illumination and maximum likelihood estimation algorithms (deconvolution) to estimate both the illumination pattern and the object (fluorophore distribution) to achieve super-resolution. Using the blind-SIM toolbox images of pollen grain and Actin network of MeT5A cells were processed and resulted in images with increased peak signal-to-noise ratio (pSNR) of 64.71 for the pollen grain and 67.04 compared to 15.21 pSNR for a widefield image of the Actin network. Processing time for an image stack comprised of 50 slices with 2691 x 2337 pixels per image was on the order of 10 hours, suggesting a processing time for a single full FOV Mesolens image of approximately 4 days. This thesis achieved proof of concept for the above-mentioned widefield optical sectioning techniques making them a viable alternative to CLSM and opened the path to tackling specific challenges for each technique.Optical sectioning in fluorescence microscopy is the process of removing out-of-focus light from the final image. Several techniques have been developed over the years and the gold standard remains confocal laser scanning microscopy (CLSM). As a point scanning instrument, a confocal microscope acquires data one pixel at a time which results in long acquisition times for large field of view (FOV), high-resolution images. Moreover, the confocal method is not useful when imaging large volume specimens with a low power, low numerical aperture (NA) lens. Hence optical sectioning techniques for widefield fluorescence imaging which use a digital camera to rapidly acquire high-resolution images are highly sought after. Widefield detection requires much less excitation light intensity allowing gentler imaging with less photobleaching and phototoxic effects simultaneously outperforming CLSM in acquisition speed.
This thesis reports the development of optical sectioning imaging modalities that have been specified to be compatible with the unique properties of the Mesolens, a novel microscope objective lens that combines millimetre scale FOV, submicron lateral resolution and a long working distance. Firstly, HiLo microscopy was adapted into HiLo mesoscopy. HiLo mesoscopy performs optical sectioning by modulating the in-focus signal with random speckle illumination while leaving out of focus signal uniform. Thus, a weighted map of the image is created that holds information of where the image is in focus and where it is out of focus. HiLo mesoscopy achieved a section thickness of 5.2±0.3 μm at an acquisition speed of 30 seconds per image pair with an additional post-processing time of ~5 minutes compared to CLSM with a section thickness of approximately 6 μm and an acquisition speed of 15 minutes for a three-frame-average final image. Next, a Gaussian light sheet illuminator was constructed using a cylindrical lens to form a light sheet that covered the field of view of the Mesolens. Although the optical section thickness was 30 μm at the center and 40 μm at the edge of the Mesolens FOV, ten times larger than the axial resolution of 7 μm of the Mesolens would require for light sheet microscopy, in optically cleared and thick specimens the out-of-focus background was reduced when compared to widefield illumination when using this simple setup. Compared to CLSM, the section capability of the Gaussian light sheet was inferior, however, the acquisition speed is only limited by the camera framerate and the photodose to the specimen was low, as can be expected from a light sheet illumination setup.
Lastly, a structured illumination microscopy (SIM) technique called blind-SIM was implemented to attempt super-resolution (SR) at the mesoscale. Blind-SIM uses random speckle illumination and maximum likelihood estimation algorithms (deconvolution) to estimate both the illumination pattern and the object (fluorophore distribution) to achieve super-resolution. Using the blind-SIM toolbox images of pollen grain and Actin network of MeT5A cells were processed and resulted in images with increased peak signal-to-noise ratio (pSNR) of 64.71 for the pollen grain and 67.04 compared to 15.21 pSNR for a widefield image of the Actin network. Processing time for an image stack comprised of 50 slices with 2691 x 2337 pixels per image was on the order of 10 hours, suggesting a processing time for a single full FOV Mesolens image of approximately 4 days. This thesis achieved proof of concept for the above-mentioned widefield optical sectioning techniques making them a viable alternative to CLSM and opened the path to tackling specific challenges for each technique
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