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Improving seismic site response analysis for non-standard sites
Get PDFEarthquake engineering aims to design and analyse structures to avoid damage in minor earthquakes and to prevent collapse in major earthquakes. An important aspect of assessing the ground motions that could occur at the basis of a structure is how the seismic waves will be affected by travelling through soil deposits near the surface. In fact, these near-surface layers act as a filter modifying (amplify/de-amplify) the input motion and leading to modified ground motions at the ground surface. Hence, the study of the effect of these near-surface layers on seismic waves is important for earthquake engineers designing and analysing structures in earthquake-prone regions.The main issues connected with assessing earthquake ground motions are the uncertainties connected with many aspects of this phenomenon: from the knowledge of the fault rupture generating the seismic waves, through the overall travel path of these waves, to the modification of the waves near the surface. In this work, I concentrate my attention on the uncertainties connected with the near-surface soil deposits. In particular, I focus on aspects of site response analysis, i.e. the modelling of the modulation of seismic waves by soil deposits. The main goal of the thesis is to improve site response analysis for "non-standard" sites, which are those for which the general assumptions of shallow (50m) of soil profiles. Very often, it is difficult to have sufficient and/or reliable in-situ measurements of the characteristics of this part of soil deposits. Therefore, it is common to take advantage of the quarter-wavelength method to assess site amplifications for these profiles because it does not need a detailed shear-wave velocity profile. In this thesis, I develop a procedure to generate randomized profiles for use within the standard site response analysis technique used for shallow deposits. This procedure uses basic information obtained from a large database of real shear-wave velocity profiles, such as length of the deep portion of the profile, the thickness of the layers and the presence of softer layers below the seismic bedrock. Finally, I compare the site amplifications using this procedure and those computed using the quarter-wavelength method and draw conclusions about when our lack of knowledge is important.Earthquake engineering aims to design and analyse structures to avoid damage in minor earthquakes and to prevent collapse in major earthquakes. An important aspect of assessing the ground motions that could occur at the basis of a structure is how the seismic waves will be affected by travelling through soil deposits near the surface. In fact, these near-surface layers act as a filter modifying (amplify/de-amplify) the input motion and leading to modified ground motions at the ground surface. Hence, the study of the effect of these near-surface layers on seismic waves is important for earthquake engineers designing and analysing structures in earthquake-prone regions.The main issues connected with assessing earthquake ground motions are the uncertainties connected with many aspects of this phenomenon: from the knowledge of the fault rupture generating the seismic waves, through the overall travel path of these waves, to the modification of the waves near the surface. In this work, I concentrate my attention on the uncertainties connected with the near-surface soil deposits. In particular, I focus on aspects of site response analysis, i.e. the modelling of the modulation of seismic waves by soil deposits. The main goal of the thesis is to improve site response analysis for "non-standard" sites, which are those for which the general assumptions of shallow (50m) of soil profiles. Very often, it is difficult to have sufficient and/or reliable in-situ measurements of the characteristics of this part of soil deposits. Therefore, it is common to take advantage of the quarter-wavelength method to assess site amplifications for these profiles because it does not need a detailed shear-wave velocity profile. In this thesis, I develop a procedure to generate randomized profiles for use within the standard site response analysis technique used for shallow deposits. This procedure uses basic information obtained from a large database of real shear-wave velocity profiles, such as length of the deep portion of the profile, the thickness of the layers and the presence of softer layers below the seismic bedrock. Finally, I compare the site amplifications using this procedure and those computed using the quarter-wavelength method and draw conclusions about when our lack of knowledge is important
Chiral resolution control in batch and continuous crystallization processes for a conglomerate forming compound
Get PDFChiral molecules are molecules that have a non-superimposable mirror image. Each of these mirror image forms is known as an enantiomer. Such molecules exist throughout nature, from amino acid and sugar molecules, to the complex helical structure of our own DNA. However, the separation of enantiomers (resolution) is extremely important in the pharmaceutical industry due to the potentially different physiochemical response that each enantiomer can induce. Where one enantiomer binds to the target receptor in the body causing the desired therapeutic response, the other enantiomer may bind to a different receptor site causing a potentially hazardous response. One of the most common resolution methods in the pharmaceutical industry is preferential crystallization. In a preferential crystallization process, supersaturated racemic (equal mixture of both enantiomers) solution is seeded with pure crystals of the preferred enantiomer. Over time these crystals grow, removing the preferred enantiomer from solution whilst the unwanted enantiomer remains in solution. Given enough time, however, nucleation of the unwanted enantiomer in the supersaturated solution is inevitable in any preferential crystallization process, batch or continuous.The work outlined in this thesis focuses on the control in both batch and continuous preferential crystallization processes by improving product enantiopurity and increasing the overall process yield and productivity compared to a conventional batch-wise preferential crystallization process. Chapter 3 addresses the issue of inevitable unwanted counter enantiomer nucleation in a batch preferential crystallization process and demonstrates a novel seeding method in which this can be avoided. A controlled concomitant preferential crystallization of both enantiomers in a single vessel is demonstrated, where a bias in the crystal size distributions of each enantiomer is exploited in order to mechanically separate pure enantiomer crystals after the crystallization process. Using this strategy any unwanted primary nucleation is avoided in the process. In Chapter 4, the simultaneous crystallization of both enantiomers in a single oscillatory baffled crystallizer is achieved whilst localizing the crystallization of each enantiomer in different sections of the crystallizer. This internally coupled system adopts the principles of a coupled batch preferential crystallization and applies it to a single reactor. The system allows the movement of solution between sections of the setup but keeps enantiomer crystals separated. The internal setup negates the need for additional tanks, pump and heating to the system. The start-up period of a continuous process before it reaches steady state generates a lot of unusable off-spec product. The aim of Chapter 5 is to identify the initial process parameters that influence the start-up time and also the robustness of the steady state that is achieved. A design of experiments approach is used to determine which initial process parameters are important such that they can be further optimized. This leads to shorter start-up times to steady state and less waste of valuable material by developing a robust steady state for the continuous process. Even in continuous operation, preferential crystallization processes are inherently unstable since nucleation of the counter enantiomer will occur in time. Therefore, in Chapter 6, a novel control strategy is demonstrated that takes back control of the continuous preferential crystallization process and allows the process to continue after nucleation of the counter enantiomer has occurred. This avoids the need to stop and restarted the process whenever the counter enantiomer crystallizes. The work in this thesis has achieved its aim in demonstrating control of preferential crystallization process in both batch and continuous platforms. The scientific progress made using new setups and strategies demonstrated have proved to be effective for chiral separation processes and have the potential to be applied on an industrial scale for the manufacture of pure chiral medicines.Chiral molecules are molecules that have a non-superimposable mirror image. Each of these mirror image forms is known as an enantiomer. Such molecules exist throughout nature, from amino acid and sugar molecules, to the complex helical structure of our own DNA. However, the separation of enantiomers (resolution) is extremely important in the pharmaceutical industry due to the potentially different physiochemical response that each enantiomer can induce. Where one enantiomer binds to the target receptor in the body causing the desired therapeutic response, the other enantiomer may bind to a different receptor site causing a potentially hazardous response. One of the most common resolution methods in the pharmaceutical industry is preferential crystallization. In a preferential crystallization process, supersaturated racemic (equal mixture of both enantiomers) solution is seeded with pure crystals of the preferred enantiomer. Over time these crystals grow, removing the preferred enantiomer from solution whilst the unwanted enantiomer remains in solution. Given enough time, however, nucleation of the unwanted enantiomer in the supersaturated solution is inevitable in any preferential crystallization process, batch or continuous.The work outlined in this thesis focuses on the control in both batch and continuous preferential crystallization processes by improving product enantiopurity and increasing the overall process yield and productivity compared to a conventional batch-wise preferential crystallization process. Chapter 3 addresses the issue of inevitable unwanted counter enantiomer nucleation in a batch preferential crystallization process and demonstrates a novel seeding method in which this can be avoided. A controlled concomitant preferential crystallization of both enantiomers in a single vessel is demonstrated, where a bias in the crystal size distributions of each enantiomer is exploited in order to mechanically separate pure enantiomer crystals after the crystallization process. Using this strategy any unwanted primary nucleation is avoided in the process. In Chapter 4, the simultaneous crystallization of both enantiomers in a single oscillatory baffled crystallizer is achieved whilst localizing the crystallization of each enantiomer in different sections of the crystallizer. This internally coupled system adopts the principles of a coupled batch preferential crystallization and applies it to a single reactor. The system allows the movement of solution between sections of the setup but keeps enantiomer crystals separated. The internal setup negates the need for additional tanks, pump and heating to the system. The start-up period of a continuous process before it reaches steady state generates a lot of unusable off-spec product. The aim of Chapter 5 is to identify the initial process parameters that influence the start-up time and also the robustness of the steady state that is achieved. A design of experiments approach is used to determine which initial process parameters are important such that they can be further optimized. This leads to shorter start-up times to steady state and less waste of valuable material by developing a robust steady state for the continuous process. Even in continuous operation, preferential crystallization processes are inherently unstable since nucleation of the counter enantiomer will occur in time. Therefore, in Chapter 6, a novel control strategy is demonstrated that takes back control of the continuous preferential crystallization process and allows the process to continue after nucleation of the counter enantiomer has occurred. This avoids the need to stop and restarted the process whenever the counter enantiomer crystallizes. The work in this thesis has achieved its aim in demonstrating control of preferential crystallization process in both batch and continuous platforms. The scientific progress made using new setups and strategies demonstrated have proved to be effective for chiral separation processes and have the potential to be applied on an industrial scale for the manufacture of pure chiral medicines
On detection of OFDM signals for cognitive radio applications
Get PDFAs the requirement for wireless telecommunications services continues to grow, it has become increasingly important to ensure that the Radio Frequency (RF) spectrum is managed efficiently. As a result of the current spectrum allocation policy, it has been found that portions of RF spectrum belonging to licensed users are often severely underutilised, at particular times and geographical locations. Awareness of this problem has led to the development of Dynamic Spectrum Access (DSA) and Cognitive Radio (CR) as possible solutions. In one variation of the shared-use model for DSA, it is proposed that the inefficient use of licensed spectrum could be overcome by enabling unlicensed users to opportunistically access the spectrum when the licensed user is not transmitting. In order for an unlicensed device to make decisions, it must be aware of its own RF environment and, therefore, it has been proposed that DSA could been abled using CR. One approach that has be identified to allow the CR to gain information about its operating environment is spectrum sensing. An interesting solution that has been identified for spectrum sensing is cyclostationary detection. This property refers to the inherent periodic nature of the second order statistics of many communications signals. One of the most common modulation formats in use today is Orthogonal Frequency Division Multiplexing (OFDM), which exhibits cyclostationarity due to the addition of a Cyclic Prefix (CP). This thesis examines several statistical tests for cyclostationarity in OFDM signals that may be used for spectrum sensing in DSA and CR. In particular, focus is placed on statistical tests that rely on estimation of the Cyclic Autocorrelation Function (CAF). Based on splitting the CAF into two complex component functions, several new statistical tests are introduced and are shown to lead to an improvement in detection performance when compared to the existing algorithms. The performance of each new algorithm is assessed in Additive White Gaussian Noise (AWGN), impulsive noise and when subjected to impairments such as multipath fading and Carrier Frequency Offset (CFO). Finally, each algorithm is targeted for Field Programmable Gate Array (FPGA) implementation using a Xilinx 7 series device. In order to keep resource costs to a minimum, it is suggested that the new algorithms are implemented on the FPGA using hardware sharing, and a simple mathematical re-arrangement of certain tests statistics is proposed to circumvent a costly division operation.As the requirement for wireless telecommunications services continues to grow, it has become increasingly important to ensure that the Radio Frequency (RF) spectrum is managed efficiently. As a result of the current spectrum allocation policy, it has been found that portions of RF spectrum belonging to licensed users are often severely underutilised, at particular times and geographical locations. Awareness of this problem has led to the development of Dynamic Spectrum Access (DSA) and Cognitive Radio (CR) as possible solutions. In one variation of the shared-use model for DSA, it is proposed that the inefficient use of licensed spectrum could be overcome by enabling unlicensed users to opportunistically access the spectrum when the licensed user is not transmitting. In order for an unlicensed device to make decisions, it must be aware of its own RF environment and, therefore, it has been proposed that DSA could been abled using CR. One approach that has be identified to allow the CR to gain information about its operating environment is spectrum sensing. An interesting solution that has been identified for spectrum sensing is cyclostationary detection. This property refers to the inherent periodic nature of the second order statistics of many communications signals. One of the most common modulation formats in use today is Orthogonal Frequency Division Multiplexing (OFDM), which exhibits cyclostationarity due to the addition of a Cyclic Prefix (CP). This thesis examines several statistical tests for cyclostationarity in OFDM signals that may be used for spectrum sensing in DSA and CR. In particular, focus is placed on statistical tests that rely on estimation of the Cyclic Autocorrelation Function (CAF). Based on splitting the CAF into two complex component functions, several new statistical tests are introduced and are shown to lead to an improvement in detection performance when compared to the existing algorithms. The performance of each new algorithm is assessed in Additive White Gaussian Noise (AWGN), impulsive noise and when subjected to impairments such as multipath fading and Carrier Frequency Offset (CFO). Finally, each algorithm is targeted for Field Programmable Gate Array (FPGA) implementation using a Xilinx 7 series device. In order to keep resource costs to a minimum, it is suggested that the new algorithms are implemented on the FPGA using hardware sharing, and a simple mathematical re-arrangement of certain tests statistics is proposed to circumvent a costly division operation
Silk fibroin nanoparticles : in vitro performance of a putative anticancer nanomedicine
Get PDFDespite the advantages of nanoparticle-based carriers for anticancer drug delivery, their translation into the clinic has been limited by factors including: (i) poor endocytic uptake and intracellular routing, (ii) macrophage clearance and (iii) a disregard of the tumour microenvironment governing nanoparticle uptake. As a result, there is a continued demand to explore the performance of polymer-based nanoparticles.;The principle hypothesis of this thesis is that silk fibroin nanoparticles can be used as anticancer nanomedicines. To validate this, the mechanisms governing drug release from silk fibroin nanoparticles are explored in Chapter 3. Next, the immunogenicity of silk fibroin nanoparticles towards macrophages is assessed (Chapter 4). Finally, Chapter 5 investigates the endocytosis of silk fibroin nanoparticles in response to the cell cycle and culture substrate mechanics.;This thesis provided the first experimental proof of lysosomotropic anticancer drug delivery from silk fibroin nanoparticles in single human breast cancer cells (Totten et al. 2017. J. Drug Target. 25, pp 865-872) (Chapter 3). Drug loaded silk fibroin nanoparticles were endocytosed by MCF-7 cells and a combination of the acidic lysosomal pH and enzymatic degradation facilitated drug release and subsequent nuclear translocation of the payload within 5 hours of dosing.;Next, nanoparticle-macrophage interactions were studied (Chapter 4). Silk fibroin nanoparticles exerted similar immunogenicity to silica and poly(lactic-co-glycolic acid) nanoparticles (Saborano, Wongpinyochit, Totten, Johnston, Seib and Duarte. 2017. Adv. Healthc. Mater. 6, 1601240). This indicated that silk fibroin nanoparticles can compete with leading healthcare materials in pre-clinical and clinical use.;Further assessment into immunomodulatory potential of silk fibroin nanoparticles revealed that they drive macrophage polarisation towards a pro-inflammatory M1-like state (Totten et al. 2019. ACS Appl. Mater. Interfaces. in press). This effect could be fine-tuned with surface modification (i.e. PEGylation). This observation is important because silk fibroin nanoparticles could act both as carriers for chemotherapeutics and as synergistic attenuators of tumour-associated macrophages in the tumour site.;Finally, advanced analysis of silk fibroin nanoparticle endocytosis was conducted (Chapter 5) by assessing intracellular trafficking in a time-dependent manner. Endocytosis of silk fibroin nanoparticles by breast cancer (MCF-7) cells was influenced by cell cycle progression, but not substrate mechanics. However, substrate mechanics were found to modulate the endocytic behaviour of healthy human (MCF-10A) breast epithelial cells. This relationship warrants further investigation with regard to the cellular response of nanomedicines.;Overall, this thesis accomplished in vitro analysis of silk fibroin nanoparticle drug delivery performance, macrophage interactions and endocytic uptake. These findings indicate that silk fibroin nanoparticles are emerging as an interesting biopolymer for anticancer applications. Work presented in this thesis provides a foundation to now move to pre-clinical in vivo studies.Despite the advantages of nanoparticle-based carriers for anticancer drug delivery, their translation into the clinic has been limited by factors including: (i) poor endocytic uptake and intracellular routing, (ii) macrophage clearance and (iii) a disregard of the tumour microenvironment governing nanoparticle uptake. As a result, there is a continued demand to explore the performance of polymer-based nanoparticles.;The principle hypothesis of this thesis is that silk fibroin nanoparticles can be used as anticancer nanomedicines. To validate this, the mechanisms governing drug release from silk fibroin nanoparticles are explored in Chapter 3. Next, the immunogenicity of silk fibroin nanoparticles towards macrophages is assessed (Chapter 4). Finally, Chapter 5 investigates the endocytosis of silk fibroin nanoparticles in response to the cell cycle and culture substrate mechanics.;This thesis provided the first experimental proof of lysosomotropic anticancer drug delivery from silk fibroin nanoparticles in single human breast cancer cells (Totten et al. 2017. J. Drug Target. 25, pp 865-872) (Chapter 3). Drug loaded silk fibroin nanoparticles were endocytosed by MCF-7 cells and a combination of the acidic lysosomal pH and enzymatic degradation facilitated drug release and subsequent nuclear translocation of the payload within 5 hours of dosing.;Next, nanoparticle-macrophage interactions were studied (Chapter 4). Silk fibroin nanoparticles exerted similar immunogenicity to silica and poly(lactic-co-glycolic acid) nanoparticles (Saborano, Wongpinyochit, Totten, Johnston, Seib and Duarte. 2017. Adv. Healthc. Mater. 6, 1601240). This indicated that silk fibroin nanoparticles can compete with leading healthcare materials in pre-clinical and clinical use.;Further assessment into immunomodulatory potential of silk fibroin nanoparticles revealed that they drive macrophage polarisation towards a pro-inflammatory M1-like state (Totten et al. 2019. ACS Appl. Mater. Interfaces. in press). This effect could be fine-tuned with surface modification (i.e. PEGylation). This observation is important because silk fibroin nanoparticles could act both as carriers for chemotherapeutics and as synergistic attenuators of tumour-associated macrophages in the tumour site.;Finally, advanced analysis of silk fibroin nanoparticle endocytosis was conducted (Chapter 5) by assessing intracellular trafficking in a time-dependent manner. Endocytosis of silk fibroin nanoparticles by breast cancer (MCF-7) cells was influenced by cell cycle progression, but not substrate mechanics. However, substrate mechanics were found to modulate the endocytic behaviour of healthy human (MCF-10A) breast epithelial cells. This relationship warrants further investigation with regard to the cellular response of nanomedicines.;Overall, this thesis accomplished in vitro analysis of silk fibroin nanoparticle drug delivery performance, macrophage interactions and endocytic uptake. These findings indicate that silk fibroin nanoparticles are emerging as an interesting biopolymer for anticancer applications. Work presented in this thesis provides a foundation to now move to pre-clinical in vivo studies
Exploring the application of ultrasonic phased arrays for industrial process analysis
Get PDFThis thesis was previously held under moratorium from 25/11/19 to 25/11/21Typical industrial process analysis techniques require an optical path to exist between the measurement sensor and the process to acquire data used to optimise and control an industrial process. Ultrasonic sensing is a well-established method to measure into optically opaque structures and highly focussed images can be generated using multiple element transducer arrays. In this Thesis, such arrays are explored as a real-time imaging tool for industrial process analysis.A novel methodology is proposed to characterise the variation between consecutive ultrasonic data sets deriving from the ultrasonic hardware. The pulse-echo response corresponding to a planar back wall acoustic interface is used to infer the bandwidth, pulse length and sensitivity of each array element. This led to the development of a calibration methodology to enhance the accuracy of experimentally generated ultrasonic images.An algorithm enabling non-invasive through-steel imaging of an industrial process is demonstrated using a simulated data set. Using principal component analysis, signals corresponding to reverberations in the steel vessel wall are identified and deselected from the ultrasonic data set prior to image construction. This facilitates the quantification of process information from the image.An image processing and object tracking algorithm are presented to quantify the bubble size distribution (BSD) and bubble velocity from ultrasonic images. When tested under controlled dynamic conditions, the mean value of the BSD was predicted within 50% at 100 mms-1 and the velocity could be predicted within 30% at 100 mms-1. However, these algorithms were sensitive to the quality of the input image to represent the true bubble shape.The consolidation of these techniques demonstrates successful application of ultrasonic phased array imaging, both invasively and noninvasively, to a dynamic process stream. Key to industrial uptake of the technology are data throughput and processing, which currently limit its applicability to real-time process analysis, and low sensitivity for some non-invasive applications.Typical industrial process analysis techniques require an optical path to exist between the measurement sensor and the process to acquire data used to optimise and control an industrial process. Ultrasonic sensing is a well-established method to measure into optically opaque structures and highly focussed images can be generated using multiple element transducer arrays. In this Thesis, such arrays are explored as a real-time imaging tool for industrial process analysis.A novel methodology is proposed to characterise the variation between consecutive ultrasonic data sets deriving from the ultrasonic hardware. The pulse-echo response corresponding to a planar back wall acoustic interface is used to infer the bandwidth, pulse length and sensitivity of each array element. This led to the development of a calibration methodology to enhance the accuracy of experimentally generated ultrasonic images.An algorithm enabling non-invasive through-steel imaging of an industrial process is demonstrated using a simulated data set. Using principal component analysis, signals corresponding to reverberations in the steel vessel wall are identified and deselected from the ultrasonic data set prior to image construction. This facilitates the quantification of process information from the image.An image processing and object tracking algorithm are presented to quantify the bubble size distribution (BSD) and bubble velocity from ultrasonic images. When tested under controlled dynamic conditions, the mean value of the BSD was predicted within 50% at 100 mms-1 and the velocity could be predicted within 30% at 100 mms-1. However, these algorithms were sensitive to the quality of the input image to represent the true bubble shape.The consolidation of these techniques demonstrates successful application of ultrasonic phased array imaging, both invasively and noninvasively, to a dynamic process stream. Key to industrial uptake of the technology are data throughput and processing, which currently limit its applicability to real-time process analysis, and low sensitivity for some non-invasive applications
Reconstructing spatially heterogeneous thermal maps using light-based metrology sensors
Get PDFModern manufacturing increasingly utilises automated systems for component positioning and assembly. Industries are interested in autonomous manufacturing as it can reduce costs and increase productivity. A vital aspect of autonomous precision manufacturing is large volume metrology. One popular approach to large volume or large scale metrology involves using light rays which travel through the air to calculate the position of an object of interest. Optical-based metrology systems like photogrammetry and laser trackers are crucial in improving the accuracy and quality associated with robotic assembly. In an industrial setting these positional measurements are subject to uncertainties which can in many instances be greater than the required tolerances. One source of uncertainty that arises when considering large scale industrial settings is light refraction (bending of the light ray path) due to temperature fluctuations in the air. This thesis will report on the recent work in using light-based sensor data to reconstruct the heterogeneous spatial map of the refractive index in the air. This is then used to discount the refractive effects and thereby reduce the uncertainty of this positioning problem. The finite element model software COMSOL Multiphysics was used to simulate light ray paths in complex, two dimensional, spatially varying temperature fields. These simulations provided a sense of the typical measurement uncertainties associated with deploying photogrammetry sensors in environments with spatially heterogeneous temperature distributions. Following this, physical experiments were carried out to assess the sensitivity of the Vicon T160 Photogrammetry system. Later chapters look at solving the inverse problem using Voronoi tessellations to spatially parameterise the refractive index map. A Bayesian approach, namely the reversible jump Markov Chain Monte Carlo method (rj-MCMC), is then used as the optimisation method in the inversion. Using the recovered refractive index map led to improvements in discounting the refractive effects by up to 54 % and the uncertainty of this positioning problem was reduced by up to 89 %. Following this, a second method was employed to reduce computational times, improve the sensitivity of the objective function and further reduce the positioning errors of the photogrammetry system. Using this second method, errors in this positioning problem were reduced by up 67 % and the uncertainty was also reduced by up to 89 %.Modern manufacturing increasingly utilises automated systems for component positioning and assembly. Industries are interested in autonomous manufacturing as it can reduce costs and increase productivity. A vital aspect of autonomous precision manufacturing is large volume metrology. One popular approach to large volume or large scale metrology involves using light rays which travel through the air to calculate the position of an object of interest. Optical-based metrology systems like photogrammetry and laser trackers are crucial in improving the accuracy and quality associated with robotic assembly. In an industrial setting these positional measurements are subject to uncertainties which can in many instances be greater than the required tolerances. One source of uncertainty that arises when considering large scale industrial settings is light refraction (bending of the light ray path) due to temperature fluctuations in the air. This thesis will report on the recent work in using light-based sensor data to reconstruct the heterogeneous spatial map of the refractive index in the air. This is then used to discount the refractive effects and thereby reduce the uncertainty of this positioning problem. The finite element model software COMSOL Multiphysics was used to simulate light ray paths in complex, two dimensional, spatially varying temperature fields. These simulations provided a sense of the typical measurement uncertainties associated with deploying photogrammetry sensors in environments with spatially heterogeneous temperature distributions. Following this, physical experiments were carried out to assess the sensitivity of the Vicon T160 Photogrammetry system. Later chapters look at solving the inverse problem using Voronoi tessellations to spatially parameterise the refractive index map. A Bayesian approach, namely the reversible jump Markov Chain Monte Carlo method (rj-MCMC), is then used as the optimisation method in the inversion. Using the recovered refractive index map led to improvements in discounting the refractive effects by up to 54 % and the uncertainty of this positioning problem was reduced by up to 89 %. Following this, a second method was employed to reduce computational times, improve the sensitivity of the objective function and further reduce the positioning errors of the photogrammetry system. Using this second method, errors in this positioning problem were reduced by up 67 % and the uncertainty was also reduced by up to 89 %
On the quantification and objective classification of instability in the healthy, osteoarthritic and prosthetic knee
Get PDFKnee instability is a common complaint in osteoarthritis (OA), and a common reasonfor revision following total knee arthroplasty (TKA). Despite this, assessment ofinstability is hampered by the lack of a validated method of objective classification orquantification, with most research relying upon patient reports of frequency ofsymptoms. The aim of this thesis is to define a theoretical framework for instability inthe knee, and to develop a protocol for the classification and quantification of instabilityin the native and prosthetic knee.Instability of the knee in this thesis is understood as the failure of the joint to return to azero-state following perturbation using all the available active and passive mechanismsavailable to it, resulting in system collapse. Symptomatic instability is the awareness ofreaching the boundary between the stable and unstable state. The prevalence ofsubjective instability in the end stage OA knee was measured from a publicly availabledatabase of pre-operative knee scores from TKA patients, while the prevalence ofinstability as a cause of revision was assessed from case note review of TKA revisionpatients from a tertiary referral orthopaedic unit. A single channel, tibia mountedaccelerometer was selected for assessment of frontal plane knee movement duringnormal walking and a protocol developed its use. This was assessed for its repeatabilityand compared with standard gait analysis in healthy volunteers, and subjectively stableand unstable post-operative TKA patients. Found to be repeatable with differentiationof output between subjectively stable and unstable TKA, the protocol was adapted andused to compare subjectively stable and unstable OA knees prior to TKA. Using patientsubjective assessment as classifier, wavelet transforms, Principal Component Analysis and linear regression was used to produce a classification model from the accelerometerdata.The single accelerometer was found to produce classification with an accuracy of84.6%, sensitivity of 93.3% and specificity of 72.7%, with area under the curve (AUC)of 0.797. This classification model for instability produces the basis from which theprotocol can be adapted and developed to improve performance and ultimate quantifyinstability in the knee for use in clinical and research settings.Knee instability is a common complaint in osteoarthritis (OA), and a common reasonfor revision following total knee arthroplasty (TKA). Despite this, assessment ofinstability is hampered by the lack of a validated method of objective classification orquantification, with most research relying upon patient reports of frequency ofsymptoms. The aim of this thesis is to define a theoretical framework for instability inthe knee, and to develop a protocol for the classification and quantification of instabilityin the native and prosthetic knee.Instability of the knee in this thesis is understood as the failure of the joint to return to azero-state following perturbation using all the available active and passive mechanismsavailable to it, resulting in system collapse. Symptomatic instability is the awareness ofreaching the boundary between the stable and unstable state. The prevalence ofsubjective instability in the end stage OA knee was measured from a publicly availabledatabase of pre-operative knee scores from TKA patients, while the prevalence ofinstability as a cause of revision was assessed from case note review of TKA revisionpatients from a tertiary referral orthopaedic unit. A single channel, tibia mountedaccelerometer was selected for assessment of frontal plane knee movement duringnormal walking and a protocol developed its use. This was assessed for its repeatabilityand compared with standard gait analysis in healthy volunteers, and subjectively stableand unstable post-operative TKA patients. Found to be repeatable with differentiationof output between subjectively stable and unstable TKA, the protocol was adapted andused to compare subjectively stable and unstable OA knees prior to TKA. Using patientsubjective assessment as classifier, wavelet transforms, Principal Component Analysis and linear regression was used to produce a classification model from the accelerometerdata.The single accelerometer was found to produce classification with an accuracy of84.6%, sensitivity of 93.3% and specificity of 72.7%, with area under the curve (AUC)of 0.797. This classification model for instability produces the basis from which theprotocol can be adapted and developed to improve performance and ultimate quantifyinstability in the knee for use in clinical and research settings
One-dimensional positive displacement pump description in cavitating conditions
Get PDFPreviously held under moratorium from 10 February 2020 until 10 March 2022The scope of the research contained in this thesis is to develop a new mathematicalalgorithm to model complex pump systems, capturing cavitationand pump behaviour. The approach consists of the solution of the hyperbolicwave equation, including compressibility and multiphase conditions.The second phase contains non-condensable gas and vapour formation, bothimportant in the density and speed of sound variation. The adopted solutionscheme is a finite volume method with a Monotonic Upwind Scheme forConservational Law (MUSCL). This algorithm is second-order accurate intime and space, with a total variation diminishing (TVD) scheme to preventspurious oscillation. In order to introduce a dissipation due to friction at thewall in a quasi-steady formulation, a source term is solved with a splittingmethod. To validate the code, the new simulation methodology was firstapplied to transient flow in a straight pipe with water hammer. The resultswere compared with results from pre-existing methodologies availablein the literature. Thereafter, the algorithm was applied to a single chamberpositive displacement diaphragm pump and then to a triplex diaphragmpump and the results compared with experimental data from an industrialtest rig for both single chamber pump and multiple triplex pump network.The simulations coped with a wide range of working pump conditions andwere capable of giving information on pressure pulsation, mass flow rateand volume fraction of the vapour formation inside the entire domain. Theresults modelled correctly the main pump behaviour especially for low cavitation formation, although cavitation was underestimated in same cases.Moreover, differences were evident out in the case of high pump rotationspeed where the vapour formation also affected the discharge phase. Forthat condition, the algorithm was not able to perform correctly, limiting theuse of the code. The algorithm may be easily extended to different positivedisplacement pump configurations, including a diaphragm pump where differentliquids are on the driven and driving sides of the diaphragm. Such ahydraulically driven diaphragm pump requires an intermediate flow whichtransfers the information from the piston to the membrane. This may beembedded in the algorithm. The capability of the new algorithm to copewith different design layouts to work as a pre-design tool has been highlightedas has its ability to simulate not only the pump behaviour but alsothe system network response to which the pump is attached. From an industrialpoint of view, a reduction in terms of simulation effort with high fidelity results permits a reduction in costs for the design process and animprovement in the knowledge of a pump's operating process. Moreover, itis possible to include the practical operation characteristic, often neglected,permitting a better estimate of the NPSHR by simulation.The scope of the research contained in this thesis is to develop a new mathematicalalgorithm to model complex pump systems, capturing cavitationand pump behaviour. The approach consists of the solution of the hyperbolicwave equation, including compressibility and multiphase conditions.The second phase contains non-condensable gas and vapour formation, bothimportant in the density and speed of sound variation. The adopted solutionscheme is a finite volume method with a Monotonic Upwind Scheme forConservational Law (MUSCL). This algorithm is second-order accurate intime and space, with a total variation diminishing (TVD) scheme to preventspurious oscillation. In order to introduce a dissipation due to friction at thewall in a quasi-steady formulation, a source term is solved with a splittingmethod. To validate the code, the new simulation methodology was firstapplied to transient flow in a straight pipe with water hammer. The resultswere compared with results from pre-existing methodologies availablein the literature. Thereafter, the algorithm was applied to a single chamberpositive displacement diaphragm pump and then to a triplex diaphragmpump and the results compared with experimental data from an industrialtest rig for both single chamber pump and multiple triplex pump network.The simulations coped with a wide range of working pump conditions andwere capable of giving information on pressure pulsation, mass flow rateand volume fraction of the vapour formation inside the entire domain. Theresults modelled correctly the main pump behaviour especially for low cavitation formation, although cavitation was underestimated in same cases.Moreover, differences were evident out in the case of high pump rotationspeed where the vapour formation also affected the discharge phase. Forthat condition, the algorithm was not able to perform correctly, limiting theuse of the code. The algorithm may be easily extended to different positivedisplacement pump configurations, including a diaphragm pump where differentliquids are on the driven and driving sides of the diaphragm. Such ahydraulically driven diaphragm pump requires an intermediate flow whichtransfers the information from the piston to the membrane. This may beembedded in the algorithm. The capability of the new algorithm to copewith different design layouts to work as a pre-design tool has been highlightedas has its ability to simulate not only the pump behaviour but alsothe system network response to which the pump is attached. From an industrialpoint of view, a reduction in terms of simulation effort with high fidelity results permits a reduction in costs for the design process and animprovement in the knowledge of a pump's operating process. Moreover, itis possible to include the practical operation characteristic, often neglected,permitting a better estimate of the NPSHR by simulation
Development of tumour-targeted delivery systems entrapping plumbagin for cancer therapy
Get PDFThis thesis was previously held under moratorium from 22 August 2019 until 22 August 2024.Plumbagin, a naphthoquinone mainly extracted from Plumbaginaceae plants, has been shown to have promising anti-cancer properties. However, its therapeutic potential is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use is further limited by its poor aqueous solubility and its rapid elimination in vivo. To overcome this limitation, we hypothesised that the entrapment of plumbagin within a delivery system conjugated to transferrin, whose receptors are overexpressed on many cancer cells, would result in a selective delivery to tumours after intravenous administration and a subsequently enhanced therapeutic efficacy. The aim of this study was to prepare and characterise transferrin-targeted delivery systems entrapping plumbagin.
In this work, we demonstrated that plumbagin could be formulated in transferrin-bearing liposomes, PLGA-PEG nanoparticles and lipid-polymer hybrid nanoparticles. The entrapment of plumbagin in these tumour-targeted nanomedicines led to an increase in plumbagin uptake by cancer cells, and improved its anti-proliferative and apoptosis activity in B16-F10, A431 and T98G cell lines compared to that observed with the drug solution. The intravenous injection of transferrin-bearing lipid-polymer hybrid nanoparticles entrapping plumbagin led to the complete tumour suppression for 40% of B16-F10 tumours. In addition, the intravenous treatment of B16-F10 tumours with transferrin-bearing liposomes and polymeric nanoparticles led to 10% tumour suppression. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any visible signs of toxicity.
In conclusion, plumbagin entrapped in these transferrin-bearing nanomedicines are therefore highly promising therapeutic systems that should be further optimised as therapeutic tools for cancer treatment.Plumbagin, a naphthoquinone mainly extracted from Plumbaginaceae plants, has been shown to have promising anti-cancer properties. However, its therapeutic potential is hampered by its failure to specifically reach tumours at a therapeutic concentration after intravenous administration, without secondary effects on normal tissues. Its use is further limited by its poor aqueous solubility and its rapid elimination in vivo. To overcome this limitation, we hypothesised that the entrapment of plumbagin within a delivery system conjugated to transferrin, whose receptors are overexpressed on many cancer cells, would result in a selective delivery to tumours after intravenous administration and a subsequently enhanced therapeutic efficacy. The aim of this study was to prepare and characterise transferrin-targeted delivery systems entrapping plumbagin.
In this work, we demonstrated that plumbagin could be formulated in transferrin-bearing liposomes, PLGA-PEG nanoparticles and lipid-polymer hybrid nanoparticles. The entrapment of plumbagin in these tumour-targeted nanomedicines led to an increase in plumbagin uptake by cancer cells, and improved its anti-proliferative and apoptosis activity in B16-F10, A431 and T98G cell lines compared to that observed with the drug solution. The intravenous injection of transferrin-bearing lipid-polymer hybrid nanoparticles entrapping plumbagin led to the complete tumour suppression for 40% of B16-F10 tumours. In addition, the intravenous treatment of B16-F10 tumours with transferrin-bearing liposomes and polymeric nanoparticles led to 10% tumour suppression. By contrast, all the tumours treated with plumbagin solution or left untreated were progressive. The animals did not show any visible signs of toxicity.
In conclusion, plumbagin entrapped in these transferrin-bearing nanomedicines are therefore highly promising therapeutic systems that should be further optimised as therapeutic tools for cancer treatment
Advanced methods of life cycle assessment for space systems
Get PDFEnvironmental Life Cycle Assessment is increasingly being applied within the space industry to scientifically quantify environmental impacts of space missions over their entire life cycle. This technique is particularly useful in early mission design phases since adverse life cycle impacts are more difficult to modify the later into the design process that they are identified. However, the use of Environmental Life Cycle Assessment does not fully align with the concept of sustainability envisioned within the 2030 Agenda for Sustainable Development which seeks to "balance the three dimensions of sustainable development: the economic, social and environmental". Despite this, combining all three sustainability dimensions within a single life cycle study has thus far never been attempted within the space industry. To address this, a new space-specific Life Cycle Sustainability Assessment framework and database was developed to assist industry advance this methodology by integrating social and economic considerations into concurrent engineering activities. This approach combines Environmental Life Cycle Assessment, Social Life Cycle Assessment and Life Cycle Costing to enable engineers to create sustainable technologies and products for space that are cost-efficient, eco-efficient and socially responsible in the frame of the 2030 Agenda. The application of the developed approach has been exemplified using case studies for the design of next generation sustainable space systems, allowing conclusions to be reached based on the interactions of each sustainability dimension during the mission design process. It is expected this approach will assist the space industry to streamline future decision-making and monitoring in a more systematic and coordinated fashion which accords with the vision of sustainability outlined in the 2030 Agenda.Environmental Life Cycle Assessment is increasingly being applied within the space industry to scientifically quantify environmental impacts of space missions over their entire life cycle. This technique is particularly useful in early mission design phases since adverse life cycle impacts are more difficult to modify the later into the design process that they are identified. However, the use of Environmental Life Cycle Assessment does not fully align with the concept of sustainability envisioned within the 2030 Agenda for Sustainable Development which seeks to "balance the three dimensions of sustainable development: the economic, social and environmental". Despite this, combining all three sustainability dimensions within a single life cycle study has thus far never been attempted within the space industry. To address this, a new space-specific Life Cycle Sustainability Assessment framework and database was developed to assist industry advance this methodology by integrating social and economic considerations into concurrent engineering activities. This approach combines Environmental Life Cycle Assessment, Social Life Cycle Assessment and Life Cycle Costing to enable engineers to create sustainable technologies and products for space that are cost-efficient, eco-efficient and socially responsible in the frame of the 2030 Agenda. The application of the developed approach has been exemplified using case studies for the design of next generation sustainable space systems, allowing conclusions to be reached based on the interactions of each sustainability dimension during the mission design process. It is expected this approach will assist the space industry to streamline future decision-making and monitoring in a more systematic and coordinated fashion which accords with the vision of sustainability outlined in the 2030 Agenda
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