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Low thrust augmented periodic orbits in the two- and three-body problems
No full textContinuous low thrust propulsion can add considerable utility to spacecraft dynamics by enabling rich new families of thrust augmented orbits. With the aim of enabling such orbits for small, low-cost spacecraft with limited on-board sensing, new families of non-Keplerian orbits are generated in the Hill-Clohessy-Wiltshire approximation using position-only feedback. The same strategy is also applied to the linearised dynamics around collinear libration points in the circular restricted three-body problem. In the Earth-Moon system, position-only feedback is used to stabilise the local dynamics, and interesting new multiply-periodic orbits are generated. The in-plane and out-of plane natural frequencies are then synchronised, allowing the generation of stable halo-type orbits of arbitrary dimensions. An application for such orbits, an Earth-Moon L2 communications relay, is also suggested. The propellant requirements for such orbits are shown to be modest and achievable with existing low thrust technology. Continuous thrust is also used to produce artificial horseshoe orbits in a two body system. Using the cylindrical-polar form of the Hill-Clohessy-Wiltshire approximation, low thrust manoeuvres are developed which allow for phased, nested constellations of spacecraft around a circular two-body orbit. Interesting new three-dimensional nested constellations can be enabled by the addition of out of-plane thrust, offering reconfigurable coverage of specific regions of the Earth. In the circular restricted three-body problem, constant thrust directed along the unit radius vector from each primary mass is applied to a spacecraft, modifying the positions and nature of the five equilibrium points, and thereby changing the region in which horseshoe orbits can occur. In the 243 Ida binary asteroid system, it is found that acceleration directed towards the two primaries results in Lyapunov-stable L4 and L5 points, permitting horseshoe orbits. In the 243 Ida system, a strategy is then proposed for finding periodic horseshoe orbits which rendezvous with the surface of the smaller primary. A search and-filter method is employed to produce initial guesses for periodic horseshoe orbits, and these guesses are then refined using a numerical shooting method to find precisely periodic orbits. However, this method misses periodic orbits with more than two crossings of the axis connecting the primaries, and is therefore modified to provide guesses for horseshoe orbits with additional crossings. Using this strategy, two thrust augmented horseshoe orbits which rendezvous with the surface of the smaller primary are found, and the speed of the spacecraft at rendezvous is shown to be small. Such orbits offer interesting new opportunities for binary asteroid touch-and-go sampling.Continuous low thrust propulsion can add considerable utility to spacecraft dynamics by enabling rich new families of thrust augmented orbits. With the aim of enabling such orbits for small, low-cost spacecraft with limited on-board sensing, new families of non-Keplerian orbits are generated in the Hill-Clohessy-Wiltshire approximation using position-only feedback. The same strategy is also applied to the linearised dynamics around collinear libration points in the circular restricted three-body problem. In the Earth-Moon system, position-only feedback is used to stabilise the local dynamics, and interesting new multiply-periodic orbits are generated. The in-plane and out-of plane natural frequencies are then synchronised, allowing the generation of stable halo-type orbits of arbitrary dimensions. An application for such orbits, an Earth-Moon L2 communications relay, is also suggested. The propellant requirements for such orbits are shown to be modest and achievable with existing low thrust technology. Continuous thrust is also used to produce artificial horseshoe orbits in a two body system. Using the cylindrical-polar form of the Hill-Clohessy-Wiltshire approximation, low thrust manoeuvres are developed which allow for phased, nested constellations of spacecraft around a circular two-body orbit. Interesting new three-dimensional nested constellations can be enabled by the addition of out of-plane thrust, offering reconfigurable coverage of specific regions of the Earth. In the circular restricted three-body problem, constant thrust directed along the unit radius vector from each primary mass is applied to a spacecraft, modifying the positions and nature of the five equilibrium points, and thereby changing the region in which horseshoe orbits can occur. In the 243 Ida binary asteroid system, it is found that acceleration directed towards the two primaries results in Lyapunov-stable L4 and L5 points, permitting horseshoe orbits. In the 243 Ida system, a strategy is then proposed for finding periodic horseshoe orbits which rendezvous with the surface of the smaller primary. A search and-filter method is employed to produce initial guesses for periodic horseshoe orbits, and these guesses are then refined using a numerical shooting method to find precisely periodic orbits. However, this method misses periodic orbits with more than two crossings of the axis connecting the primaries, and is therefore modified to provide guesses for horseshoe orbits with additional crossings. Using this strategy, two thrust augmented horseshoe orbits which rendezvous with the surface of the smaller primary are found, and the speed of the spacecraft at rendezvous is shown to be small. Such orbits offer interesting new opportunities for binary asteroid touch-and-go sampling
Development of novel unicondylar knee implants for use with robotic orthopaedic tools
Get PDFThe print copy of the thesis contains a CD at the back that has appendices (appendix 1-16).Knee arthroplasty surgeries have become an increasingly common procedure in orthopaedics, especially for younger patients. New robotic technology has been introduced into the orthopaedic surgery with good results. The robotic technology is versatile to use and it then opens up the development of potential novel prosthetic designs. This project investigates one type of knee arthroplasty - the unicondylar knee arthroplasty (pseudonyms: unicondylar (or unicompartmental) knee arthroplasty (or replacement) abbreviated to UKA or UKR); and how it can be improved by robotic technology.;The project followed a design process applying a range of methods to generate as many different prosthesis concepts, and then to organise and evaluate the concepts in a systematic manner. The strongest ideas were highlighted and, where possible, were developed into experiments. Some of the experiments were conducted practically in the lab while others were carried out by computer simulations.;The project was able to provide constructive insight into novel prosthesis features and provide two prosthesis prototypes fashioned from the concepts. From the final two concepts, the BQ concept was picked due to the overall performance in the experimentation.Knee arthroplasty surgeries have become an increasingly common procedure in orthopaedics, especially for younger patients. New robotic technology has been introduced into the orthopaedic surgery with good results. The robotic technology is versatile to use and it then opens up the development of potential novel prosthetic designs. This project investigates one type of knee arthroplasty - the unicondylar knee arthroplasty (pseudonyms: unicondylar (or unicompartmental) knee arthroplasty (or replacement) abbreviated to UKA or UKR); and how it can be improved by robotic technology.;The project followed a design process applying a range of methods to generate as many different prosthesis concepts, and then to organise and evaluate the concepts in a systematic manner. The strongest ideas were highlighted and, where possible, were developed into experiments. Some of the experiments were conducted practically in the lab while others were carried out by computer simulations.;The project was able to provide constructive insight into novel prosthesis features and provide two prosthesis prototypes fashioned from the concepts. From the final two concepts, the BQ concept was picked due to the overall performance in the experimentation
Signal processing-enhanced laser-based infrared spectroscopy
Get PDFIn this dissertation, a portfolio of three projects is presented where intracavity embodiment of optical parametric oscillators (OPO) and various signal processing tools applied to the data they produced are the common factors in all the work done during this programme. Two demonstrated projects were based on a study of new potential applications for commercialised OPO based imaging system, while in the last one the unmatched characteristics of such a system were exploited, in order to develop new embodiment of a spectroscopic technique.;The INHERIt project explored the use of hyperspectral imaging technologies, combined with advanced signal processing techniques, for the purpose of automatically recognising counterfeit paintings. Various challenges associated with laser based imaging are discussed as well as hardware based solutions to resolve some of these issues are proposed. The application of classification techniques was demonstrated based on the data acquired from both bespoke and actual forged paintings.;The Rosdam project aimed to evaluate two types of hyperspectral imaging systems, as well as their capability and applicability for the detection of oil spillages in ice-affected waters. This work lead to the conclusion that the employed technology was not suitable for oil under ice detection. The undertaken experimental approach is explained, the treatment of oil and ice is discussed and the findings and lessons learned during this work are presented.;The IC-OPO-PAS project aimed to develop an optical molecular gas sensor exhibiting high levels of selectivity and sensitivity. The outstanding sensitivity demonstrated by this technology is rooted in a novel combination of photoacoustic spectroscopy (PAS) operated within the cavity of a continuous-wave, Intracavity OPO. In this work detection at the level of single parts-per-billion (ppb) is shown and a discussion on how this technology could be readily refined to potentially demonstrate a sensitivity of 10's parts-per-quadrillion (ppq) is presented.;This thesis revealed a successful combination of seemingly two independent fields of science which, when utilised together, can provide superior results. Moreover, it demonstrated the need for broadly tuneable laser sources operating in infrared spectral region. Overall conclusions are given in this portfolio of presented above projects and possible future research opportunities are discussed in the context of the results obtained over the course of this programme.In this dissertation, a portfolio of three projects is presented where intracavity embodiment of optical parametric oscillators (OPO) and various signal processing tools applied to the data they produced are the common factors in all the work done during this programme. Two demonstrated projects were based on a study of new potential applications for commercialised OPO based imaging system, while in the last one the unmatched characteristics of such a system were exploited, in order to develop new embodiment of a spectroscopic technique.;The INHERIt project explored the use of hyperspectral imaging technologies, combined with advanced signal processing techniques, for the purpose of automatically recognising counterfeit paintings. Various challenges associated with laser based imaging are discussed as well as hardware based solutions to resolve some of these issues are proposed. The application of classification techniques was demonstrated based on the data acquired from both bespoke and actual forged paintings.;The Rosdam project aimed to evaluate two types of hyperspectral imaging systems, as well as their capability and applicability for the detection of oil spillages in ice-affected waters. This work lead to the conclusion that the employed technology was not suitable for oil under ice detection. The undertaken experimental approach is explained, the treatment of oil and ice is discussed and the findings and lessons learned during this work are presented.;The IC-OPO-PAS project aimed to develop an optical molecular gas sensor exhibiting high levels of selectivity and sensitivity. The outstanding sensitivity demonstrated by this technology is rooted in a novel combination of photoacoustic spectroscopy (PAS) operated within the cavity of a continuous-wave, Intracavity OPO. In this work detection at the level of single parts-per-billion (ppb) is shown and a discussion on how this technology could be readily refined to potentially demonstrate a sensitivity of 10's parts-per-quadrillion (ppq) is presented.;This thesis revealed a successful combination of seemingly two independent fields of science which, when utilised together, can provide superior results. Moreover, it demonstrated the need for broadly tuneable laser sources operating in infrared spectral region. Overall conclusions are given in this portfolio of presented above projects and possible future research opportunities are discussed in the context of the results obtained over the course of this programme
Customers' behavioural contribution to the service encounter
Get PDFThe dyadic nature of the service encounter suggests that the service output essentially arises from the coordinated efforts of customers and service employees. In this view, the services marketing literature has recently trended towards incorporating customer positive behaviours into the study of the interpersonal dynamics of the service encounter, thereby hinting that customers' behavioural contributions are conducive to achieving a positive service outcome.;However, the manner in which such positive service encounters can develop at the customer's initiative lacks empirical evidence. This research adopts a behavioural perspective and draws on the fact that service encounters are reciprocal in nature; this means that service employee behaviour can often come as a response to the customer's prior behaviour, and can therefore be more reactive in nature.;A mixed-methods sequential exploratory research design, implemented through two studies, aimed at advancing the current understanding on the ways that customers can contribute to the service encounter through the impact of their behaviour on service employees' subsequent behavioural response.;Study 1 was exploratory and employed in-depth interviews conducted among service employees, in order to investigate the effect of customer positive behaviours from the recipients' standpoint. The results revealed that service employees engage in favourable reciprocal behaviours towards customers who benefited them during the service encounter. Moreover, these customer benefits are translated into resources that enhance service employees' overall performance, as well as the enjoyment derived from delivering the service to all customers.;Study 2 used an online scenario-based experimental survey distributed among service employees, so as to test a theoretical model linking customer behaviour to service employee behaviour, mediated by the service employee's experience. The results confirmed the initial hypothesis according to which customer discretionary behaviours can initiate a cyclical process of exchange of positive behaviours among the parties involved in the service encounter, through their beneficial impact on service employees' experience.;Overall, this research advances our limited theoretical knowledge on the interpersonal dynamics of the service encounter, by offering empirical evidence on the role of customer behaviour as an antecedent to subsequent service employee behaviour. Therefore, the thesis reinforces the argument according to which customers are partially responsible for the service outcome they receive, as they have the ability to enhance the development of a mutually beneficial service encounter through their behaviour towards service employees.The dyadic nature of the service encounter suggests that the service output essentially arises from the coordinated efforts of customers and service employees. In this view, the services marketing literature has recently trended towards incorporating customer positive behaviours into the study of the interpersonal dynamics of the service encounter, thereby hinting that customers' behavioural contributions are conducive to achieving a positive service outcome.;However, the manner in which such positive service encounters can develop at the customer's initiative lacks empirical evidence. This research adopts a behavioural perspective and draws on the fact that service encounters are reciprocal in nature; this means that service employee behaviour can often come as a response to the customer's prior behaviour, and can therefore be more reactive in nature.;A mixed-methods sequential exploratory research design, implemented through two studies, aimed at advancing the current understanding on the ways that customers can contribute to the service encounter through the impact of their behaviour on service employees' subsequent behavioural response.;Study 1 was exploratory and employed in-depth interviews conducted among service employees, in order to investigate the effect of customer positive behaviours from the recipients' standpoint. The results revealed that service employees engage in favourable reciprocal behaviours towards customers who benefited them during the service encounter. Moreover, these customer benefits are translated into resources that enhance service employees' overall performance, as well as the enjoyment derived from delivering the service to all customers.;Study 2 used an online scenario-based experimental survey distributed among service employees, so as to test a theoretical model linking customer behaviour to service employee behaviour, mediated by the service employee's experience. The results confirmed the initial hypothesis according to which customer discretionary behaviours can initiate a cyclical process of exchange of positive behaviours among the parties involved in the service encounter, through their beneficial impact on service employees' experience.;Overall, this research advances our limited theoretical knowledge on the interpersonal dynamics of the service encounter, by offering empirical evidence on the role of customer behaviour as an antecedent to subsequent service employee behaviour. Therefore, the thesis reinforces the argument according to which customers are partially responsible for the service outcome they receive, as they have the ability to enhance the development of a mutually beneficial service encounter through their behaviour towards service employees
Towards understanding 'knowledge workers' lived experience of service productivity in the banking sector
No full textThe problem domain of the study presented in this thesis is the lived experience of service productivity. Particularly, the study is concerned with the lived experience of service productivity of bank executives working as 'official knowledge workers' in the Nigerian banking sector. This group of employees are those that met the 'fit and proper persons' criteria set by the banking sector regulatory authorities and authorised to handle 'key control functions' in their banks. This group of employees are designated 'official knowledge workers' in this study. The research question formulated for the study is: "What is the lived experience of service productivity of the official knowledge workers in the Nigerian banking sector?" The first part of the study was a review of the service operations and knowledge management literature followed by synthesis, which yielded conceptual results. The empirical part was a qualitative study that involved face to face interviews with sixteen Nigerian bank executives from five Nigerian banks. Each interviewee gave a detailed account of their lived experiences of service productivity. The empirical material gathered was analysed using a phenomenological research method developed as part of this research, which I named 'Trans Positional Cognition Approach' (TPCA), and it constitutes the methodological contribution of the thesis. TPCA synthesises the principles of both the descriptive and interpretive phenomenological schools of thoughts and helps researchers to overcome the divide between the two schools of thought and follow a more inclusive approach. Through the analysis of the study data, I identified the existence of 'internal and external' service capacity deficit related factors that impact on the productive inputs of the official knowledge workers resulting in the incidence of what can be referred to as 'lost productivity', which implies a gap in these workers measures of productivity. I have used the Viable System Model principle of Normative Planning developed by Stafford Beer to better explain/understand the factors that constrain both the capability and potential productivity of the official knowledge workers. This is then expressed in greater detail in two academic models, the Official Knowledge Workers Productivity Challenge (oKWPC) and Official Knowledge Worker Productive Input (oKWPI) models developed as part of this research. Hence, this work contributes to scholarly knowledge on service productivity from the official knowledge workers perspective.The problem domain of the study presented in this thesis is the lived experience of service productivity. Particularly, the study is concerned with the lived experience of service productivity of bank executives working as 'official knowledge workers' in the Nigerian banking sector. This group of employees are those that met the 'fit and proper persons' criteria set by the banking sector regulatory authorities and authorised to handle 'key control functions' in their banks. This group of employees are designated 'official knowledge workers' in this study. The research question formulated for the study is: "What is the lived experience of service productivity of the official knowledge workers in the Nigerian banking sector?" The first part of the study was a review of the service operations and knowledge management literature followed by synthesis, which yielded conceptual results. The empirical part was a qualitative study that involved face to face interviews with sixteen Nigerian bank executives from five Nigerian banks. Each interviewee gave a detailed account of their lived experiences of service productivity. The empirical material gathered was analysed using a phenomenological research method developed as part of this research, which I named 'Trans Positional Cognition Approach' (TPCA), and it constitutes the methodological contribution of the thesis. TPCA synthesises the principles of both the descriptive and interpretive phenomenological schools of thoughts and helps researchers to overcome the divide between the two schools of thought and follow a more inclusive approach. Through the analysis of the study data, I identified the existence of 'internal and external' service capacity deficit related factors that impact on the productive inputs of the official knowledge workers resulting in the incidence of what can be referred to as 'lost productivity', which implies a gap in these workers measures of productivity. I have used the Viable System Model principle of Normative Planning developed by Stafford Beer to better explain/understand the factors that constrain both the capability and potential productivity of the official knowledge workers. This is then expressed in greater detail in two academic models, the Official Knowledge Workers Productivity Challenge (oKWPC) and Official Knowledge Worker Productive Input (oKWPI) models developed as part of this research. Hence, this work contributes to scholarly knowledge on service productivity from the official knowledge workers perspective
Millimetre and sub-millimetre wave input couplers for gyrotron travelling wave amplifiers
Get PDFThe input coupler is an important component for a microwave amplifier. A sidewall single-hole input coupler for a W-band gyrotron travelling-wave amplifier that operates at the frequency range of 90-100 GHz was designed and measured. Instead of using a cutoff waveguide, a broadband Bragg-type reflector with a small spread in phase was optimized for use as part of the input coupler. The minimum radius of the reflector was two times the size of a cutoff waveguide, which reduced the possibility for some of the beam electrons being collected in this section and lost to the amplifier interaction region. The design, simulation, construction and measurement of a W-band waveguide input coupler that used a backstop Bragg reflector that allowed for high electron beam transmission from a cusp electron beam source into a 3-fold helically corrugated interaction waveguide (HCIW) of a gyrotron travelling wave amplifier is presented. Experimental results are reported of a broadband, high power, gyrotron traveling wave amplifier (gyro-TWA) operating in the 75-110 GHz frequency band. The second harmonic cyclotron mode of a 55 keV, 1.5 A, axis-encircling electron beam was used to resonantly interact with a traveling TE₂₁-like eigenwave, achieving broadband amplification. The gyro-TWA demonstrated a 3 dB gain bandwidth of at least 5.5 GHz in the experimental measurement with 9 GHz predicted for a wideband drive source with a measured unsaturated output power of 3.4 kW and gain of 36-38 dB. The inclusion of the Bragg reflector in the W-band waveguide input coupler enabled efficient (4.4%) beam-wave interaction to be achieved within the gyro-TWA.;The design of 1) a T-junction fundamental mode rectangular to- circular waveguide input coupler, 2) a multiple-hole input coupler and 3) a higher order mode (HOM) input coupler for a low-terahertz gyrotron travelling wave amplifier were studied. The T-junction input coupler with a Bragg reflector and a multiple-hole directional coupler were optimized for operation between 360 and 384 GHz, the proposed bandwidth of a low THz gyro TWA. The T-junction coupler and the multiple-hole coupler achieved the respective bandwidths of 10% and 35%.A higher order mode (HOM) two-branch waveguide coupler based on the even distribution of incident power was designed to couple the rectangular TE₁₀ mode to the circular TE₆₁ mode. The optimised tapered waveguide input coupler achieved an operating frequency range of 359-385 GHz, equating to a bandwidth of 7%. A prototype waveguide coupler scaled to W-band (75-110 GHz) was manufactured. The vector network analyser measured return loss of the HOM coupler was shown to be <10 dB at 90-96 GHz. A transmission and phase measurement is presented to analyse TE₆₁ mode conversion in the HOM coupler.The input coupler is an important component for a microwave amplifier. A sidewall single-hole input coupler for a W-band gyrotron travelling-wave amplifier that operates at the frequency range of 90-100 GHz was designed and measured. Instead of using a cutoff waveguide, a broadband Bragg-type reflector with a small spread in phase was optimized for use as part of the input coupler. The minimum radius of the reflector was two times the size of a cutoff waveguide, which reduced the possibility for some of the beam electrons being collected in this section and lost to the amplifier interaction region. The design, simulation, construction and measurement of a W-band waveguide input coupler that used a backstop Bragg reflector that allowed for high electron beam transmission from a cusp electron beam source into a 3-fold helically corrugated interaction waveguide (HCIW) of a gyrotron travelling wave amplifier is presented. Experimental results are reported of a broadband, high power, gyrotron traveling wave amplifier (gyro-TWA) operating in the 75-110 GHz frequency band. The second harmonic cyclotron mode of a 55 keV, 1.5 A, axis-encircling electron beam was used to resonantly interact with a traveling TE₂₁-like eigenwave, achieving broadband amplification. The gyro-TWA demonstrated a 3 dB gain bandwidth of at least 5.5 GHz in the experimental measurement with 9 GHz predicted for a wideband drive source with a measured unsaturated output power of 3.4 kW and gain of 36-38 dB. The inclusion of the Bragg reflector in the W-band waveguide input coupler enabled efficient (4.4%) beam-wave interaction to be achieved within the gyro-TWA.;The design of 1) a T-junction fundamental mode rectangular to- circular waveguide input coupler, 2) a multiple-hole input coupler and 3) a higher order mode (HOM) input coupler for a low-terahertz gyrotron travelling wave amplifier were studied. The T-junction input coupler with a Bragg reflector and a multiple-hole directional coupler were optimized for operation between 360 and 384 GHz, the proposed bandwidth of a low THz gyro TWA. The T-junction coupler and the multiple-hole coupler achieved the respective bandwidths of 10% and 35%.A higher order mode (HOM) two-branch waveguide coupler based on the even distribution of incident power was designed to couple the rectangular TE₁₀ mode to the circular TE₆₁ mode. The optimised tapered waveguide input coupler achieved an operating frequency range of 359-385 GHz, equating to a bandwidth of 7%. A prototype waveguide coupler scaled to W-band (75-110 GHz) was manufactured. The vector network analyser measured return loss of the HOM coupler was shown to be <10 dB at 90-96 GHz. A transmission and phase measurement is presented to analyse TE₆₁ mode conversion in the HOM coupler
Metabolic reprogramming of dendritic cells by intracellular protozoan parasites
Get PDFThis thesis was previously held under moratorium from 11th September 2019 until 11th September 2024.Upon activation, immune cells such as macrophages and dendritic cells alter their metabolism to support phagocytosis, antigen processing, cytokine production and T cell activation. Even in an oxygenated environment, immune cells change their metabolism from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. This is referred to as the ‘Warburg effect’. Aerobic glycolysis benefits the immune response by rapidly generating ATP whilst disruption of OXPHOS results in accumulation of intermediate metabolites which are used for other immunological purposes. The situation is further complicated by intracellular pathogens that compete for host resources or even manipulate metabolic pathways for their own gain. To combat this, hosts have evolved mechanisms to restrict the availability of certain metabolites to suppress pathogen growth. The following studies were undertaken to determine the
interplay between DCs and Leishmania and Toxoplasma. A polyomics approach comprising of transcriptomic and metabolic analyses validated with functional assays was employed to investigate the effect of L. mexicana or T. gondii on the BMDC phenotype. The data observes transcript and metabolic changes including aerobic glycolysis and reduced oxidative phosphorylation demonstrating the Warburg effect. Consistent with this, LDH activity was upregulated and mitochondrial membrane potential reduced in L. mexicana and T. gondii infected BMDC cultures. In addition, certain changes to BMDC metabolism would appear to be parasite evolved to promote their growth and survival. In L. mexicana infected BMDCs, accumulation of itaconate (a TCA intermediate) could be associated with the reduction of pro-inflammatory
cytokine production. Furthermore, changes in arginine metabolism including upregulation of arginase, ornithine and proline production were observed in T. gondii infected BMDCs and are likely to reflect the coevolution of parasite and host. These results highlight the complex interplay of host and parasite metabolism with the developing immune response in BMDCs.Upon activation, immune cells such as macrophages and dendritic cells alter their metabolism to support phagocytosis, antigen processing, cytokine production and T cell activation. Even in an oxygenated environment, immune cells change their metabolism from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. This is referred to as the ‘Warburg effect’. Aerobic glycolysis benefits the immune response by rapidly generating ATP whilst disruption of OXPHOS results in accumulation of intermediate metabolites which are used for other immunological purposes. The situation is further complicated by intracellular pathogens that compete for host resources or even manipulate metabolic pathways for their own gain. To combat this, hosts have evolved mechanisms to restrict the availability of certain metabolites to suppress pathogen growth. The following studies were undertaken to determine the
interplay between DCs and Leishmania and Toxoplasma. A polyomics approach comprising of transcriptomic and metabolic analyses validated with functional assays was employed to investigate the effect of L. mexicana or T. gondii on the BMDC phenotype. The data observes transcript and metabolic changes including aerobic glycolysis and reduced oxidative phosphorylation demonstrating the Warburg effect. Consistent with this, LDH activity was upregulated and mitochondrial membrane potential reduced in L. mexicana and T. gondii infected BMDC cultures. In addition, certain changes to BMDC metabolism would appear to be parasite evolved to promote their growth and survival. In L. mexicana infected BMDCs, accumulation of itaconate (a TCA intermediate) could be associated with the reduction of pro-inflammatory
cytokine production. Furthermore, changes in arginine metabolism including upregulation of arginase, ornithine and proline production were observed in T. gondii infected BMDCs and are likely to reflect the coevolution of parasite and host. These results highlight the complex interplay of host and parasite metabolism with the developing immune response in BMDCs
Measuring client modes of engagement in humanistic experiential psychotherapy
Get PDFThe role of clients' emotional engagement has progressively played a central role in psychotherapy. This project inserts itself in this debate by seeking to validate the Client Modes of Engagement (CME) theoretical model (Elliott 2006; 2013a). While Elliott's CME framework-a process-diagnostic map based on clients' experiential content-was grounded on decades of research and clinical practice, it had yet to be made amenable to empirical investigation.;This project responds to this absence by offering the Client Modes of Engagement Observational Coding System (CME-OCS) and the Client Modes of Engagement Questionnaire (CMEQ-R2). These instruments measure the construct from both the perspective of external observers (CME-OCS) and therapists (CMEQ-R2).;This dissertation explores the application and validation process for both the CME-OCS and the CMEQ-R2. The results confirmed that the CME-OCS is a reliable coding system for identifying CMEs during EFT psychotherapy. Additionally, the findings suggest that there are interactions between CMEs, phases of therapy, and outcome groups. Moreover, I established that there are differences in the ways outcome groups' transition between CMEs at particular stages of therapy.;I applied both classical psychometric properties methods and Rasch modelling with the purpose of examining the CMEQ-R2's psychometrics, refining the instrument, and later applying it in a process outcome study. The results suggest that levels of CME early in therapy and changes in levels of CME over therapy-as measured by the CMEQ-R2-are significantly associated with client pre-post therapeutic improvement.;I also found firm ground for arguing that therapists can distinguish between levels of CMEs and that their perspective can be systematically analysed. Together, both instruments pose important implications for research and clinical practice. Overall, this study validates the contention that researchers and therapists should be particularly attentive to clients' manner of engagement and focus of attention on specific levels of their emotion scheme.The role of clients' emotional engagement has progressively played a central role in psychotherapy. This project inserts itself in this debate by seeking to validate the Client Modes of Engagement (CME) theoretical model (Elliott 2006; 2013a). While Elliott's CME framework-a process-diagnostic map based on clients' experiential content-was grounded on decades of research and clinical practice, it had yet to be made amenable to empirical investigation.;This project responds to this absence by offering the Client Modes of Engagement Observational Coding System (CME-OCS) and the Client Modes of Engagement Questionnaire (CMEQ-R2). These instruments measure the construct from both the perspective of external observers (CME-OCS) and therapists (CMEQ-R2).;This dissertation explores the application and validation process for both the CME-OCS and the CMEQ-R2. The results confirmed that the CME-OCS is a reliable coding system for identifying CMEs during EFT psychotherapy. Additionally, the findings suggest that there are interactions between CMEs, phases of therapy, and outcome groups. Moreover, I established that there are differences in the ways outcome groups' transition between CMEs at particular stages of therapy.;I applied both classical psychometric properties methods and Rasch modelling with the purpose of examining the CMEQ-R2's psychometrics, refining the instrument, and later applying it in a process outcome study. The results suggest that levels of CME early in therapy and changes in levels of CME over therapy-as measured by the CMEQ-R2-are significantly associated with client pre-post therapeutic improvement.;I also found firm ground for arguing that therapists can distinguish between levels of CMEs and that their perspective can be systematically analysed. Together, both instruments pose important implications for research and clinical practice. Overall, this study validates the contention that researchers and therapists should be particularly attentive to clients' manner of engagement and focus of attention on specific levels of their emotion scheme
Optimal experimental design and its applications to biochemical engineering systems
Get PDFThis work is motivated by challenges in data-based modelling of complex systems due to limited information of sparse and noisy experimental data. Optimal experimental design (OED) techniques, which aim at devising necessary experiments to generate informative measurement data to facilitate model identification, have been investigated comprehensively.The limitations of existing experimental design approaches have been extensively discussed, based on which advanced experimental design methods and efficient numerical strategies have been developed for improved solutions.;Two case study biochemical systems have been used through the research investigation, one is an enzyme reaction system, the other one is a lab-scale enzymatic biodiesel production system. The main contributions of this PhD work can be summarised as follows:;Single objective experimental designs by considering one type of design factors, i.e. input intensity, measurement set selection, sampling profile design, respectively, has been formulated and numerical strategies to solve these optimisation problems have been described in detail. Implementations of these design methods to biochemical systems have demonstrated its efficiency in reducing parameter estimation errors.;A new OED strategy has been proposed to cope with OED problems including multiple design factors in one optimisation framework. An iterative two-layer design structure is developed. In the lower layer for observation design, the sampling profile and the measurement set selection are combined and formulated as a single integrated observation design problem, which is relaxed to a convex optimization problem that can be solved with a local method.;Thus the measurement set selection and the sampling profile can be determined simultaneously. In the upper layer for input design, the optimisation of input intensities is obtained through stochastic global searching. In this way, the multi-factor optimisation problem is solved through the integration of a stochastic method, for the upper layer, and a deterministic method, for the lower layer.;A new enzyme reaction model has been established which represents a typical class of enzymatic kinetically controlled synthesis process. This model contains important kinetic reaction features, moderate complexity, and complete model information. It can be used as a benchmark problem for development and comparison of OED algorithms. Systematic analysis has been performed in order to examine the system behaviours, and the dependence on model parameters, initial operation conditions.;Structural identifiability and practical identifiability of this system have been analysed and identifiable parameters determined. The design of experiment for the enzyme reactionsystem by considering different types of design variables have been investigated. The parameter estimation precision can be improved significantly by using the proposed OED techniques, compared to the non-designed condition.;The OED techniques are numerically investigated based on a lab-scale biodiesel production process with real experimental data through research collaboration with DTU in Denmark. The OED applications on this real system model allow to examine the effectiveness and efficiency of those new proposed OED methods. The measurement set selection and the sampling design of this system are developed which provide detailed instructions on how to improve experiments through OED.;Also, the sensitivity analysis and parameter identifiability analysis are conducted; and their impacts to experimental design are clearly identified.This work is motivated by challenges in data-based modelling of complex systems due to limited information of sparse and noisy experimental data. Optimal experimental design (OED) techniques, which aim at devising necessary experiments to generate informative measurement data to facilitate model identification, have been investigated comprehensively.The limitations of existing experimental design approaches have been extensively discussed, based on which advanced experimental design methods and efficient numerical strategies have been developed for improved solutions.;Two case study biochemical systems have been used through the research investigation, one is an enzyme reaction system, the other one is a lab-scale enzymatic biodiesel production system. The main contributions of this PhD work can be summarised as follows:;Single objective experimental designs by considering one type of design factors, i.e. input intensity, measurement set selection, sampling profile design, respectively, has been formulated and numerical strategies to solve these optimisation problems have been described in detail. Implementations of these design methods to biochemical systems have demonstrated its efficiency in reducing parameter estimation errors.;A new OED strategy has been proposed to cope with OED problems including multiple design factors in one optimisation framework. An iterative two-layer design structure is developed. In the lower layer for observation design, the sampling profile and the measurement set selection are combined and formulated as a single integrated observation design problem, which is relaxed to a convex optimization problem that can be solved with a local method.;Thus the measurement set selection and the sampling profile can be determined simultaneously. In the upper layer for input design, the optimisation of input intensities is obtained through stochastic global searching. In this way, the multi-factor optimisation problem is solved through the integration of a stochastic method, for the upper layer, and a deterministic method, for the lower layer.;A new enzyme reaction model has been established which represents a typical class of enzymatic kinetically controlled synthesis process. This model contains important kinetic reaction features, moderate complexity, and complete model information. It can be used as a benchmark problem for development and comparison of OED algorithms. Systematic analysis has been performed in order to examine the system behaviours, and the dependence on model parameters, initial operation conditions.;Structural identifiability and practical identifiability of this system have been analysed and identifiable parameters determined. The design of experiment for the enzyme reactionsystem by considering different types of design variables have been investigated. The parameter estimation precision can be improved significantly by using the proposed OED techniques, compared to the non-designed condition.;The OED techniques are numerically investigated based on a lab-scale biodiesel production process with real experimental data through research collaboration with DTU in Denmark. The OED applications on this real system model allow to examine the effectiveness and efficiency of those new proposed OED methods. The measurement set selection and the sampling design of this system are developed which provide detailed instructions on how to improve experiments through OED.;Also, the sensitivity analysis and parameter identifiability analysis are conducted; and their impacts to experimental design are clearly identified
Modelling the nanoscale properties of calcium silicate hydrate and ice
Get PDFThis thesis was previously held under moratorium from 20/02/19 to 25/05/2021.Cement is the most widely used construction material in the world. It can sustain substantial load due to its high compressive strength but is vulnerable to cracks due to its quasi-brittle nature. Calcium silicate hydrate, the origin of strength in cement, is a complex, nano-crystalline material. An understanding of the structure-property relationships of calcium silicate hydrate at the nanoscale is of great importance in order to modify the structure for improved mechanical properties.;Molecular dynamics simulation studies are often used to investigate nanoscale materials and rely upon an accurate chemical structure and force field bonding description of the system. For cementitious materials, however, there is no established force field. ReaxFF, a reactive force field which can account for the creation and breaking of chemical bonds, has shown promise in the literature for simulation of the mechanical properties of calcium silicate hydrates. However, little evidence of validation of the force field for describing calcium silicate hydrates has been seen in the literature. Furthermore, the lack of experimental data for comparison makes validation of the simulation methods difficult.;One material which has been studied extensively both experimentally and in simulations, and is also of engineering importance, is ice Ih. In this work, ReaxFF is shown to make excellent predictions of the structure and physical properties of ice Ih and makes reasonable comparisons to experimentally measured elastic constants. A fracture simulation protocol has been designed and produces realistic values of fracture toughness and fracture speeds of ice Ih showing improvements over existing simulation studies.;By employing methods validated using ice Ih, this thesis goes on to predict the structure-property relationships of calcium silicate hydrate. It is revealed that the structure-property relationship is strongly correlated to chemical composition and therefore altering the ratio of the starting products in cement has the potential to lead to a product with tailor-made mechanical properties. Additionally, this thesis gives an insight into the tensile failure of calcium silicate hydrate at the nanoscale and highlights the challenges in simulating fracture such as the very high strain rate which must be adopted in simulations or the inability to model polycrystalline structures.Cement is the most widely used construction material in the world. It can sustain substantial load due to its high compressive strength but is vulnerable to cracks due to its quasi-brittle nature. Calcium silicate hydrate, the origin of strength in cement, is a complex, nano-crystalline material. An understanding of the structure-property relationships of calcium silicate hydrate at the nanoscale is of great importance in order to modify the structure for improved mechanical properties.;Molecular dynamics simulation studies are often used to investigate nanoscale materials and rely upon an accurate chemical structure and force field bonding description of the system. For cementitious materials, however, there is no established force field. ReaxFF, a reactive force field which can account for the creation and breaking of chemical bonds, has shown promise in the literature for simulation of the mechanical properties of calcium silicate hydrates. However, little evidence of validation of the force field for describing calcium silicate hydrates has been seen in the literature. Furthermore, the lack of experimental data for comparison makes validation of the simulation methods difficult.;One material which has been studied extensively both experimentally and in simulations, and is also of engineering importance, is ice Ih. In this work, ReaxFF is shown to make excellent predictions of the structure and physical properties of ice Ih and makes reasonable comparisons to experimentally measured elastic constants. A fracture simulation protocol has been designed and produces realistic values of fracture toughness and fracture speeds of ice Ih showing improvements over existing simulation studies.;By employing methods validated using ice Ih, this thesis goes on to predict the structure-property relationships of calcium silicate hydrate. It is revealed that the structure-property relationship is strongly correlated to chemical composition and therefore altering the ratio of the starting products in cement has the potential to lead to a product with tailor-made mechanical properties. Additionally, this thesis gives an insight into the tensile failure of calcium silicate hydrate at the nanoscale and highlights the challenges in simulating fracture such as the very high strain rate which must be adopted in simulations or the inability to model polycrystalline structures
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