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Nonlinear control : an LPV nonlinear predictive generalised minimum variance perspective
Get PDFThis thesis describes new developments in nonlinear controllers for industrial applications. It first introduces the Nonlinear Generalised Minimum Variance (NGMV) control algorithm, for Linear Parameter Varying systems (LPV). This combines the benefits of the basic NGMV algorithm in dealing with nonlinearities, where a black box input model can be used, and adds an option to also approximate a nonlinear system with an LPV output subsystem. The models can therefore represent LPV systems and characteristics including saturation, discontinuities and time-varying dynamics. The next major contribution is in the nonlinear predictive control algorithms proposed that are also using the LPV model structure. The simplest is the Nonlinear Generalized Predictive Control (NGPC) algorithm that relates to the best known model predictive control law for linear systems. The final predictive control solution is one that may be specialized to either the NGMV or NGPC cases and is therefore the most general. This is referred to as a Nonlinear Predictive Generalized Minimum Variance Controller (NPGMV). When the algorithms use only the LPV structure to approximate the nonlinear system the solutions are particularly simple in unconstrained and constrained versions, and are relatively light computationally for implementation. Three representative industrial design examples have been chosen to validate the algorithms for different Bandwidth (BW) and nonlinear characteristics. All three examples were based on real application problems with company interest. In the first example (small BW) the basic state-space and LPV versions of the algorithm are used for the auto-manoeuvring and dynamic positioning of marine vessel. In this application the parameter variations were representative of wave disturbance changes with sea state, rather than due to approximating nonlinear behaviour. Actuator constraints were considered in the design. In the second industrial example (medium BW) the LPV-NPGMV was implemented for controlling the blade pitch and generator torque of a 5MW offshore wind turbine. The main objective here was to maintain the power produced at the rated value which requires compensation against wind disturbances, so that wind speed is the varying parameter. The LPV-NPGMV controller produced here used a parameterised system model involving the wind speed so that the controller performance changed with wind conditions. Actuator constraints were included and statistical performance assessed. The third example (fast BW) explores the stabilisation of a 2-axis gyroscopic electro-optical turret used in surveillance applications. This application was designed and employed on a real system. Because of the limitations imposed by BW requirements and the memory of the digital controller, only the basic state-space version of the algorithm was possible to implement. The main objective in this problem was to improve the tracking performance around the NADIR singularity point (a discontinuity) in the trajectory. In all three examples the NGMV controllers showed notable improvement in comparison to the baseline controllers without the need for scheduled gains or re-configuration when moving across different operating points.This thesis describes new developments in nonlinear controllers for industrial applications. It first introduces the Nonlinear Generalised Minimum Variance (NGMV) control algorithm, for Linear Parameter Varying systems (LPV). This combines the benefits of the basic NGMV algorithm in dealing with nonlinearities, where a black box input model can be used, and adds an option to also approximate a nonlinear system with an LPV output subsystem. The models can therefore represent LPV systems and characteristics including saturation, discontinuities and time-varying dynamics. The next major contribution is in the nonlinear predictive control algorithms proposed that are also using the LPV model structure. The simplest is the Nonlinear Generalized Predictive Control (NGPC) algorithm that relates to the best known model predictive control law for linear systems. The final predictive control solution is one that may be specialized to either the NGMV or NGPC cases and is therefore the most general. This is referred to as a Nonlinear Predictive Generalized Minimum Variance Controller (NPGMV). When the algorithms use only the LPV structure to approximate the nonlinear system the solutions are particularly simple in unconstrained and constrained versions, and are relatively light computationally for implementation. Three representative industrial design examples have been chosen to validate the algorithms for different Bandwidth (BW) and nonlinear characteristics. All three examples were based on real application problems with company interest. In the first example (small BW) the basic state-space and LPV versions of the algorithm are used for the auto-manoeuvring and dynamic positioning of marine vessel. In this application the parameter variations were representative of wave disturbance changes with sea state, rather than due to approximating nonlinear behaviour. Actuator constraints were considered in the design. In the second industrial example (medium BW) the LPV-NPGMV was implemented for controlling the blade pitch and generator torque of a 5MW offshore wind turbine. The main objective here was to maintain the power produced at the rated value which requires compensation against wind disturbances, so that wind speed is the varying parameter. The LPV-NPGMV controller produced here used a parameterised system model involving the wind speed so that the controller performance changed with wind conditions. Actuator constraints were included and statistical performance assessed. The third example (fast BW) explores the stabilisation of a 2-axis gyroscopic electro-optical turret used in surveillance applications. This application was designed and employed on a real system. Because of the limitations imposed by BW requirements and the memory of the digital controller, only the basic state-space version of the algorithm was possible to implement. The main objective in this problem was to improve the tracking performance around the NADIR singularity point (a discontinuity) in the trajectory. In all three examples the NGMV controllers showed notable improvement in comparison to the baseline controllers without the need for scheduled gains or re-configuration when moving across different operating points
Supply chain risk management : exploring an integrated process for managing interdependent risks and risk mitigation strategies
No full textThe goal of this research is to investigate interdependency modelling of supply chain risks, and to develop and empirically evaluate a supply chain risk management process that not only integrates all stages of the process but also captures interdependencies between risks and risk mitigation strategies. The proposed process is tailored to the risk management needs of both conventional and project driven supply chains. Project driven supply chains necessitate experimenting untested (unique) strategies depending on the level of project complexity whereas in the case of conventional supply chains, there is generally a consensus in establishing interdependencies between risks and the efficacy of strategies. A systematic literature review methodology was employed to identify research gaps and establish the research agenda. In order to gain an insight into industrial practice, empirical research was conducted in South Australia involving semi-structured interviews with experts in project risk management that resulted in the development of a project complexity and risk management (ProCRiM) process. The research gaps identified and the findings of the empirical research helped in developing dependency based probabilistic supply chain risk measures that can be readily used for assessing and managing risks associated with global supply chains. In order to capture interdependencies between supply chain risks, strategies and performance measures, two case studies were conducted in reputed supply chains involving semi-structured interviews and focus group sessions that resulted in the development of two risk management frameworks: an adapted version of ProCRiM applicable to project driven supply chains and a framework specific to conventional supply chains. The research also focused on investigating the merits and challenges associated with implementing the proposed process. In order to capture the risk appetite of a decision maker, a process namely supply chain risk network management is developed and illustrated through a simulation study.The goal of this research is to investigate interdependency modelling of supply chain risks, and to develop and empirically evaluate a supply chain risk management process that not only integrates all stages of the process but also captures interdependencies between risks and risk mitigation strategies. The proposed process is tailored to the risk management needs of both conventional and project driven supply chains. Project driven supply chains necessitate experimenting untested (unique) strategies depending on the level of project complexity whereas in the case of conventional supply chains, there is generally a consensus in establishing interdependencies between risks and the efficacy of strategies. A systematic literature review methodology was employed to identify research gaps and establish the research agenda. In order to gain an insight into industrial practice, empirical research was conducted in South Australia involving semi-structured interviews with experts in project risk management that resulted in the development of a project complexity and risk management (ProCRiM) process. The research gaps identified and the findings of the empirical research helped in developing dependency based probabilistic supply chain risk measures that can be readily used for assessing and managing risks associated with global supply chains. In order to capture interdependencies between supply chain risks, strategies and performance measures, two case studies were conducted in reputed supply chains involving semi-structured interviews and focus group sessions that resulted in the development of two risk management frameworks: an adapted version of ProCRiM applicable to project driven supply chains and a framework specific to conventional supply chains. The research also focused on investigating the merits and challenges associated with implementing the proposed process. In order to capture the risk appetite of a decision maker, a process namely supply chain risk network management is developed and illustrated through a simulation study
Formulation of non-ionic surfactant vesicles for therapeutic delivery of siRNA in cancer treatment
Get PDFRNA interference (RNAi) is a post-transcriptional gene regulatory mechanism that involves the degradation of a target messenger RNA (mRNA) through the incorporation of short interfering RNAs (siRNA) which is complementary to the target mRNA. Unmodified, naked siRNA is unstable and cannot freely penetrate the cell membrane. The application of siRNA based therapeutics is limited by the development of an effective delivery system to deliver therapeutic siRNA to the cytoplasm of the target cells. Lipid-based nanoparticles, such as liposomes, are the most commonly investigated systems for siRNA delivery. However, another type of lipid-based system known as non-ionic surfactant vesicles (NISV) which are commonly used for drug delivery of various therapeutic agents, are relatively safe and non-expensive have not been extensively studied for siRNA delivery. Therefore, the aim of this study was to investigate the potential of NISV in siRNA delivery. Different manufacturing methods are used for the preparation of NISV and most of them are limited to bench scale and cannot be used on a larger industrial scale. This project sought to optimise the formulation method of NISV and to investigate their potential to effectively deliver siRNA to tumour cells in vitro and in vivo. Different methods of NISV manufacturing were compared including: thin-film hydration method (TFH), heating method, and microfluidic mixing. The formation of spherical nanoparticles was confirmed by examining the morphology of the NISV prepared by the three methods with atomic force microscopy (AFM) or scanning electron microscopy (SEM). TFH and heating methods were able to produce small (< 200 nm) and homogeneous NISV only after using a post-manufacturing size reduction step such as extrusion. This was time consuming and it was difficult to control batch to batch variations. Microfluidic mixing was found to produce NISV of the desired size and dispersity required for regulatory approval, in a single step, without the need of size reduction and homogenisation. Moreover, the preparation time was significantly reduced with controllable parameters, which suggested this method would make production feasible on a larger scale.;Therefore, microfluidic mixing was chosen to prepare different NISV formulations and to investigate the optimisation of the factors related to this method, including the mixing time, mixing ratio, and the type of hydration media used. These were found to have significant effects on the physical characteristics of the vesicles such as size, polydispersity index, and charge. Particle size was shown to be decreased significantly (p<0.05) by increasing the ratio between the aqueous and lipid phase as well as by increasing the total flow rates in the mixing process. Optimum ratios were found to be 3:1 between the aqueous and lipid phase at a total flow rates of 12 ml/min. Moreover, changing the type of aqueous media used to prepare the particles also resulted in significant effects on the particle size, dispersity, and charge. Smaller particles (desirable for siRNA delivery) were obtained using distilled water (DW), Tris, and (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES) buffers while the use of phosphate buffered saline (PBS) or normal saline (NS) resulted in the preparation of larger particles. Therefore, for the next experiments that involved siRNA transfections, NISV were prepared with DW. After optimising all these parameters, in vitro studies were conducted with the NISV formulations made with either monopalmitin glycerol (MPG) or Tween85 (T85) as a non-ionic surfactant, in addition to cholesterol and dimethyldioctadecylammonium bromide (DDAB) as a charging material, at different molar ratios of these components. Cytotoxicity evaluation of the prepared NISV formulations were carried out on non-small lung cancer cells (A549), human melanoma cancer cells (A375), breast cancer cells (A780), and mouse melanoma cells (B16-F10-LUC). These experiments were carried out with the use of normal human prostate cells PNT2) as a control. The used cancer cell lines were selected as they are among the most abundant cancers types worldwide. Cytotoxicity studies indicated that all the NISV formulations were not toxic at or below 40 μg/ml. The prepared NISV formulations had high siRNA encapsulation efficiency (~90%). Fluorescent microscope and flow cytometry studies on A549 cells, using fluorescent labelled negative control siRNA loaded in all the NISV formulations tested, indicated high cellular uptake by the cells.;These uptake results were confirmed with B16-F10-LUC mouse melanoma cells, where the prepared NISV were able to successfully deliver siRNA into the cells compared to naked siRNA, which was not taken up by the cells. Following these experiments that proved cellular uptake of siRNA delivered by NISV, siRNA targeting either green fluorescent protein (GFP) in copGFP-A549 cells, or luciferase enzyme in B16-F10-LUC cells were encapsulated in NISV that contained either MPG or T85 as a non-ionic surfactant. Inhibition of GFP expression by anti-GFP siRNA (siGFP) delivered using different NISV formulations was evaluated by fluorescence measurement, flow cytometry, polymerase chain reaction, and Western blotting studies. These results indicated that all the NISV formulations were able to deliver siGFP to the cells and significantly (p<0.05) suppress GFP expression. These results were confirmed by transfecting the luciferase producing B16-F10-LUC cells with anti-luciferase siRNA (siLUC) using the same NISV formulations. Measuring the level of luciferase expression after siLUC transfections using a luciferase protein assay system successfully demonstrated the suppression of luciferase expression. Among all the NISV prepared, significant GFP and luciferase gene knockdown results were achieved when using NISV that contained T85 as the non-ionic surfactant. This superior formulation was then used in in vivo experiments using nude BALB/c mice inoculated with B16-F10-LUC cells that induce melanoma cancer-expressing luciferase. After intra-tumoural injection with this formulation, siLUC was delivered to the cells and suppressed luciferase expression at a significantly (p<0.05) higher level than mice treated with naked siLUC. These in vivo results confirm the ability of NISV to successfully delivery siRNA into the cytoplasm of the target tumour cells and suppress the target protein. In conclusion, NISV prepared by microfluidics have been demonstrated extensively and for the first time to have the potential to be used as a delivery system for siRNA. These results have shown that NISV can be used to overcome the barriers, such as low stability and poor cellular uptake, in siRNA-based therapeutics. NISV are a promising delivery system which can be investigated more extensively to target different over-expressed proteins in the process of developing different effective cancer medications.RNA interference (RNAi) is a post-transcriptional gene regulatory mechanism that involves the degradation of a target messenger RNA (mRNA) through the incorporation of short interfering RNAs (siRNA) which is complementary to the target mRNA. Unmodified, naked siRNA is unstable and cannot freely penetrate the cell membrane. The application of siRNA based therapeutics is limited by the development of an effective delivery system to deliver therapeutic siRNA to the cytoplasm of the target cells. Lipid-based nanoparticles, such as liposomes, are the most commonly investigated systems for siRNA delivery. However, another type of lipid-based system known as non-ionic surfactant vesicles (NISV) which are commonly used for drug delivery of various therapeutic agents, are relatively safe and non-expensive have not been extensively studied for siRNA delivery. Therefore, the aim of this study was to investigate the potential of NISV in siRNA delivery. Different manufacturing methods are used for the preparation of NISV and most of them are limited to bench scale and cannot be used on a larger industrial scale. This project sought to optimise the formulation method of NISV and to investigate their potential to effectively deliver siRNA to tumour cells in vitro and in vivo. Different methods of NISV manufacturing were compared including: thin-film hydration method (TFH), heating method, and microfluidic mixing. The formation of spherical nanoparticles was confirmed by examining the morphology of the NISV prepared by the three methods with atomic force microscopy (AFM) or scanning electron microscopy (SEM). TFH and heating methods were able to produce small (< 200 nm) and homogeneous NISV only after using a post-manufacturing size reduction step such as extrusion. This was time consuming and it was difficult to control batch to batch variations. Microfluidic mixing was found to produce NISV of the desired size and dispersity required for regulatory approval, in a single step, without the need of size reduction and homogenisation. Moreover, the preparation time was significantly reduced with controllable parameters, which suggested this method would make production feasible on a larger scale.;Therefore, microfluidic mixing was chosen to prepare different NISV formulations and to investigate the optimisation of the factors related to this method, including the mixing time, mixing ratio, and the type of hydration media used. These were found to have significant effects on the physical characteristics of the vesicles such as size, polydispersity index, and charge. Particle size was shown to be decreased significantly (p<0.05) by increasing the ratio between the aqueous and lipid phase as well as by increasing the total flow rates in the mixing process. Optimum ratios were found to be 3:1 between the aqueous and lipid phase at a total flow rates of 12 ml/min. Moreover, changing the type of aqueous media used to prepare the particles also resulted in significant effects on the particle size, dispersity, and charge. Smaller particles (desirable for siRNA delivery) were obtained using distilled water (DW), Tris, and (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid) (HEPES) buffers while the use of phosphate buffered saline (PBS) or normal saline (NS) resulted in the preparation of larger particles. Therefore, for the next experiments that involved siRNA transfections, NISV were prepared with DW. After optimising all these parameters, in vitro studies were conducted with the NISV formulations made with either monopalmitin glycerol (MPG) or Tween85 (T85) as a non-ionic surfactant, in addition to cholesterol and dimethyldioctadecylammonium bromide (DDAB) as a charging material, at different molar ratios of these components. Cytotoxicity evaluation of the prepared NISV formulations were carried out on non-small lung cancer cells (A549), human melanoma cancer cells (A375), breast cancer cells (A780), and mouse melanoma cells (B16-F10-LUC). These experiments were carried out with the use of normal human prostate cells PNT2) as a control. The used cancer cell lines were selected as they are among the most abundant cancers types worldwide. Cytotoxicity studies indicated that all the NISV formulations were not toxic at or below 40 μg/ml. The prepared NISV formulations had high siRNA encapsulation efficiency (~90%). Fluorescent microscope and flow cytometry studies on A549 cells, using fluorescent labelled negative control siRNA loaded in all the NISV formulations tested, indicated high cellular uptake by the cells.;These uptake results were confirmed with B16-F10-LUC mouse melanoma cells, where the prepared NISV were able to successfully deliver siRNA into the cells compared to naked siRNA, which was not taken up by the cells. Following these experiments that proved cellular uptake of siRNA delivered by NISV, siRNA targeting either green fluorescent protein (GFP) in copGFP-A549 cells, or luciferase enzyme in B16-F10-LUC cells were encapsulated in NISV that contained either MPG or T85 as a non-ionic surfactant. Inhibition of GFP expression by anti-GFP siRNA (siGFP) delivered using different NISV formulations was evaluated by fluorescence measurement, flow cytometry, polymerase chain reaction, and Western blotting studies. These results indicated that all the NISV formulations were able to deliver siGFP to the cells and significantly (p<0.05) suppress GFP expression. These results were confirmed by transfecting the luciferase producing B16-F10-LUC cells with anti-luciferase siRNA (siLUC) using the same NISV formulations. Measuring the level of luciferase expression after siLUC transfections using a luciferase protein assay system successfully demonstrated the suppression of luciferase expression. Among all the NISV prepared, significant GFP and luciferase gene knockdown results were achieved when using NISV that contained T85 as the non-ionic surfactant. This superior formulation was then used in in vivo experiments using nude BALB/c mice inoculated with B16-F10-LUC cells that induce melanoma cancer-expressing luciferase. After intra-tumoural injection with this formulation, siLUC was delivered to the cells and suppressed luciferase expression at a significantly (p<0.05) higher level than mice treated with naked siLUC. These in vivo results confirm the ability of NISV to successfully delivery siRNA into the cytoplasm of the target tumour cells and suppress the target protein. In conclusion, NISV prepared by microfluidics have been demonstrated extensively and for the first time to have the potential to be used as a delivery system for siRNA. These results have shown that NISV can be used to overcome the barriers, such as low stability and poor cellular uptake, in siRNA-based therapeutics. NISV are a promising delivery system which can be investigated more extensively to target different over-expressed proteins in the process of developing different effective cancer medications
Non-Newtonian effects and Taylor-Aris despersion in rivulet flow
Get PDFIn this thesis we use a combination of analytical and numerical methods to analyse two aspects of the steady flow of rivulets of fluid, namely the effects of non-Newtonian rheology, and the transport of a passive solute in a rivulet of Newtonian fluid. In Chapters 2-4 we consider rivulet flow of non-Newtonian fluids. Firstly, we obtain the solution for unidirectional gravity-driven flow of a uniform thin rivulet of a power-law fluid down a planar substrate, and then we use this solution to describe the flow of a rivulet with prescribed constant contact angle but slowly varying semi-width down a slowly varying substrate, specifically the flow in the azimuthal direction around the outside of a large horizontal circular cylinder. Secondly, we use the solution for unidirectional flow to describe the flow of arivulet with prescribed constant semi-width but slowly varying contact angledown a slowly varying substrate. Thirdly, we consider rivulet flow of generalised Newtonian fluids down a vertical planar substrate. In particular, we obtain the solutions for rivulet flow of a Carreau fluid and of an Ellis fluid, highlighting their similarities and differences. In Chapters 5 and 6 we investigate both the short-time advection and the long-time Taylor-Aris dispersion of a passive solute in uniform non-thin and thin rivulets, respectively, of a Newtonian fluid undergoing steady unidirectional flow driven by gravity and/or a prescribed uniform surface shear stress on a verticalplanar substrate. In particular, we obtain an explicit expression for the effective diffusivity of the solute in a thin rivulet as a function of the surface shear stress, the volume flux along the rivulet, and either the semi-width or the contact angle of the rivulet.In this thesis we use a combination of analytical and numerical methods to analyse two aspects of the steady flow of rivulets of fluid, namely the effects of non-Newtonian rheology, and the transport of a passive solute in a rivulet of Newtonian fluid. In Chapters 2-4 we consider rivulet flow of non-Newtonian fluids. Firstly, we obtain the solution for unidirectional gravity-driven flow of a uniform thin rivulet of a power-law fluid down a planar substrate, and then we use this solution to describe the flow of a rivulet with prescribed constant contact angle but slowly varying semi-width down a slowly varying substrate, specifically the flow in the azimuthal direction around the outside of a large horizontal circular cylinder. Secondly, we use the solution for unidirectional flow to describe the flow of arivulet with prescribed constant semi-width but slowly varying contact angledown a slowly varying substrate. Thirdly, we consider rivulet flow of generalised Newtonian fluids down a vertical planar substrate. In particular, we obtain the solutions for rivulet flow of a Carreau fluid and of an Ellis fluid, highlighting their similarities and differences. In Chapters 5 and 6 we investigate both the short-time advection and the long-time Taylor-Aris dispersion of a passive solute in uniform non-thin and thin rivulets, respectively, of a Newtonian fluid undergoing steady unidirectional flow driven by gravity and/or a prescribed uniform surface shear stress on a verticalplanar substrate. In particular, we obtain an explicit expression for the effective diffusivity of the solute in a thin rivulet as a function of the surface shear stress, the volume flux along the rivulet, and either the semi-width or the contact angle of the rivulet
Knowledge management in innovative technology companies : the case of the energy sector
Get PDFKnowledge Management (KM) has been extensively researched for more than two decades, however the academic literature is still quite disjoined and fragmented. Companies keep facing repetitive KM-related problems that come at high cost, and the solutions that they find are often reduced to installing a new software package that is expected to facilitate knowledge flow across an organisation.This research departs from a problem observed in practice - a failed KM project in an innovative company, and aims at understanding the reasons behind this failure. It then investigates KM within some of the most innovative companies in the energy sector in an attempt to address the questions found in practice and not answered by the academic literature. Subsequently it sets the following research goals, which help to address identified gaps in the literature: (1) to understand the KM journey that companies undertake, (2) to define the role of technology in this journey, and (2) to explore gamification as a possible contributing aspect of a developed solution.The research adopts an iterative approach in a form of continuous dialogue between theory and practice, with multiple case study analysis as the research design of the main part of the empirical investigation. And as a result, it develops an organic roadmap of KM that depicts an evolution of KM in innovative companies at the example of the energy sector.This research contributes of the body of knowledge by:1. Describing a KM journey that innovative companies in the energy sector undertake in order to achieve excellence, and that consists of three phases: managing explicit knowledge, knowledge sharing and creating new knowledge.2. Demonstrating that technological component (document repositories) is central to KM only in the first phase and becomes peripheral (with the most useful tool being wikis) starting from the second phase.3. Opening a new area of research and suggesting that gamification might have a significant impact on KM that stretches far beyond motivation.4. Questioning that maturity models are an appropriate framework to study the evolution of KM in an organisation.The research contributes to practice by demonstrating that KM is a learning process rather than a one-time initiative and by creating realistic expectations from the technological support.The extent of the contribution was discussed with the companies-participants of this study and the board of directors at Durham Energy Institute, being a validation of the findings.Knowledge Management (KM) has been extensively researched for more than two decades, however the academic literature is still quite disjoined and fragmented. Companies keep facing repetitive KM-related problems that come at high cost, and the solutions that they find are often reduced to installing a new software package that is expected to facilitate knowledge flow across an organisation.This research departs from a problem observed in practice - a failed KM project in an innovative company, and aims at understanding the reasons behind this failure. It then investigates KM within some of the most innovative companies in the energy sector in an attempt to address the questions found in practice and not answered by the academic literature. Subsequently it sets the following research goals, which help to address identified gaps in the literature: (1) to understand the KM journey that companies undertake, (2) to define the role of technology in this journey, and (2) to explore gamification as a possible contributing aspect of a developed solution.The research adopts an iterative approach in a form of continuous dialogue between theory and practice, with multiple case study analysis as the research design of the main part of the empirical investigation. And as a result, it develops an organic roadmap of KM that depicts an evolution of KM in innovative companies at the example of the energy sector.This research contributes of the body of knowledge by:1. Describing a KM journey that innovative companies in the energy sector undertake in order to achieve excellence, and that consists of three phases: managing explicit knowledge, knowledge sharing and creating new knowledge.2. Demonstrating that technological component (document repositories) is central to KM only in the first phase and becomes peripheral (with the most useful tool being wikis) starting from the second phase.3. Opening a new area of research and suggesting that gamification might have a significant impact on KM that stretches far beyond motivation.4. Questioning that maturity models are an appropriate framework to study the evolution of KM in an organisation.The research contributes to practice by demonstrating that KM is a learning process rather than a one-time initiative and by creating realistic expectations from the technological support.The extent of the contribution was discussed with the companies-participants of this study and the board of directors at Durham Energy Institute, being a validation of the findings
A tissue-engineered approach to hernia repair
Get PDFHernia repairs are among the most common surgical procedures performed, with more than 20 million hernias estimated to be repaired every year around the world. Mesh insertion is the most common method of treatment, with the mesh typically being made from polypropylene (PP). Significant complications can arise from PP meshes that include chronic infection, inflammation and pain. Electrospinning, a technique that utilises electric forces to create micro- and nanofibres, was used to fabricate a new-generation of hernia mesh (drug-loaded polymeric mesh). Solutions of polycaprolactone (PCL) or polylactic acid (PLA), two aliphatic polymers commonly used in various clinical applications, were individually mixed with irgasan (IRG) (an antibacterial agent) or levofloxacin (LEVO) (a broad-spectrum antibiotic). Type I collagen was later included into the polymer-drug solutions in order to increase the biocompatibility of the samples. Electrospun samples were subsequently analysed for mechanical, physicochemical, drug release and biological characteristics. Electrospinning was useful in creating micro- and nano- fibres for polymer-drug combinations. IRG-loaded scaffolds displayed a sustained release behaviour, whilst LEVO-loaded scaffolds showed a burst release. The addition of type I collagen modified the release rate of PLA-LEVO scaffolds from burst to sustained release, and modified surface characteristics from hydrophilic to hydrophobic. Biological studies demonstrated smooth muscle cells affinity to LEVO-loaded scaffolds, with high adhesion and proliferation, whilst also demonstrating significant resistance to bacterial growth (E. coli and S. aureus).Hernia repairs are among the most common surgical procedures performed, with more than 20 million hernias estimated to be repaired every year around the world. Mesh insertion is the most common method of treatment, with the mesh typically being made from polypropylene (PP). Significant complications can arise from PP meshes that include chronic infection, inflammation and pain. Electrospinning, a technique that utilises electric forces to create micro- and nanofibres, was used to fabricate a new-generation of hernia mesh (drug-loaded polymeric mesh). Solutions of polycaprolactone (PCL) or polylactic acid (PLA), two aliphatic polymers commonly used in various clinical applications, were individually mixed with irgasan (IRG) (an antibacterial agent) or levofloxacin (LEVO) (a broad-spectrum antibiotic). Type I collagen was later included into the polymer-drug solutions in order to increase the biocompatibility of the samples. Electrospun samples were subsequently analysed for mechanical, physicochemical, drug release and biological characteristics. Electrospinning was useful in creating micro- and nano- fibres for polymer-drug combinations. IRG-loaded scaffolds displayed a sustained release behaviour, whilst LEVO-loaded scaffolds showed a burst release. The addition of type I collagen modified the release rate of PLA-LEVO scaffolds from burst to sustained release, and modified surface characteristics from hydrophilic to hydrophobic. Biological studies demonstrated smooth muscle cells affinity to LEVO-loaded scaffolds, with high adhesion and proliferation, whilst also demonstrating significant resistance to bacterial growth (E. coli and S. aureus)
A distance adaptable brain-computer interface based on steady-state visual evoked potential
Get PDFBrain-computer interfaces (BCI) provide an alternative communication channel which does not rely on the brain's normal output pathway between patients suffering from neuromuscular diseases and their external environment. BCI requires at least one brain signal as input in order to interpret the intent of the user. Non-invasive electroencephalography (EEG) is the most common and favourite method for acquiring brain signals. In the last two decades, several EEG based BCIs have been developed to help these patients. The brain signals which can be recorded in EEG and used as the input for BCIs include motor sensory rhythm, slow cortical potential, P300 and steady-state visual evoked potential (SSVEP). Compared to the other EEG based BCI paradigms, SSVEP based BCI has the advantage of high information transfer rate, high detection rate, less user training time required and commands scalability. Furthermore, SSVEP based BCI is normally operated in the self paced mode which is more intuitive and practical for real world applications. Recently, SSVEP based BCIs have attracted great attention in the field of BCI research. While most SSVEP BCI studies focus on the improvement of signal detection and classification accuracy, there is a need to bridge the gap between BCI research and practice in the real world. SSVEP based BCI requires an external visual stimulator to elicit SSVEP response. Currently, for most SSVEP based BCIs the viewing distances between the visual stimulator and the users are less than 100cm, limiting the usability and flexibility of BCI and its potential applications and users. This study proposes a novel distance adaptable SSVEP BCI paradigm which allows its users to operate the system from a range of viewing distances between the user and the visual stimulator. Unlike the conventional SSVEP BCI where users can only operate the system when they are sitting in front of the visual stimulator at a fixed distance which is normally less than 100cm, in our proposed system, users can operate the BCI at any viewing distance within the range in this proposed BCI. It is hoped that the proposed BCI system can improve the usability and the flexibility of BCI and also broaden the range of potential applications and users. For example, it can be used by older people with degenerating mobility or by patients with impaired mobility in the care environment to support their independence. Moreover, it can also be used by healthy people in a smart home or for a game control environment. The primary goal of the present study is to investigate the feasibility of the proposed distance adaptable SSVEP based BCI. This study first investigates the impact of the viewing distance on SSVEP response and compensates the deteriorated SSVEP resulting from the viewing distance by changing the intensities of the visual stimuli. 10 healthy subjects participate in the experiment to assess the feasibility of the distance adaptable SSVEP based BCI. The feasibility of the system is evaluated by the classification performance of off-line experiments at different viewing distances. The classification accuracies of the proposed BCI are examined by different EEG time window lengths, number of SSVEP harmonics and the number of recording electrodes employed. This study also investigates the sources of deterioration of SSVEP detection in BCI setup and proposes an electrode ranking method to select the recording electrodes for the implementation of the real time on line system. The experimental results demonstrate that a distance adaptable SSVEP BCI is achievable and that electrodes chosen by the proposed electrode ranking method outperform electrodes chosen by random selection in classification performance.Brain-computer interfaces (BCI) provide an alternative communication channel which does not rely on the brain's normal output pathway between patients suffering from neuromuscular diseases and their external environment. BCI requires at least one brain signal as input in order to interpret the intent of the user. Non-invasive electroencephalography (EEG) is the most common and favourite method for acquiring brain signals. In the last two decades, several EEG based BCIs have been developed to help these patients. The brain signals which can be recorded in EEG and used as the input for BCIs include motor sensory rhythm, slow cortical potential, P300 and steady-state visual evoked potential (SSVEP). Compared to the other EEG based BCI paradigms, SSVEP based BCI has the advantage of high information transfer rate, high detection rate, less user training time required and commands scalability. Furthermore, SSVEP based BCI is normally operated in the self paced mode which is more intuitive and practical for real world applications. Recently, SSVEP based BCIs have attracted great attention in the field of BCI research. While most SSVEP BCI studies focus on the improvement of signal detection and classification accuracy, there is a need to bridge the gap between BCI research and practice in the real world. SSVEP based BCI requires an external visual stimulator to elicit SSVEP response. Currently, for most SSVEP based BCIs the viewing distances between the visual stimulator and the users are less than 100cm, limiting the usability and flexibility of BCI and its potential applications and users. This study proposes a novel distance adaptable SSVEP BCI paradigm which allows its users to operate the system from a range of viewing distances between the user and the visual stimulator. Unlike the conventional SSVEP BCI where users can only operate the system when they are sitting in front of the visual stimulator at a fixed distance which is normally less than 100cm, in our proposed system, users can operate the BCI at any viewing distance within the range in this proposed BCI. It is hoped that the proposed BCI system can improve the usability and the flexibility of BCI and also broaden the range of potential applications and users. For example, it can be used by older people with degenerating mobility or by patients with impaired mobility in the care environment to support their independence. Moreover, it can also be used by healthy people in a smart home or for a game control environment. The primary goal of the present study is to investigate the feasibility of the proposed distance adaptable SSVEP based BCI. This study first investigates the impact of the viewing distance on SSVEP response and compensates the deteriorated SSVEP resulting from the viewing distance by changing the intensities of the visual stimuli. 10 healthy subjects participate in the experiment to assess the feasibility of the distance adaptable SSVEP based BCI. The feasibility of the system is evaluated by the classification performance of off-line experiments at different viewing distances. The classification accuracies of the proposed BCI are examined by different EEG time window lengths, number of SSVEP harmonics and the number of recording electrodes employed. This study also investigates the sources of deterioration of SSVEP detection in BCI setup and proposes an electrode ranking method to select the recording electrodes for the implementation of the real time on line system. The experimental results demonstrate that a distance adaptable SSVEP BCI is achievable and that electrodes chosen by the proposed electrode ranking method outperform electrodes chosen by random selection in classification performance
Control of Shigella sonnei and adhesive invasive Escherichia coli infections with a natural product which inhibits the bacterial oxidoreductase DsbA
Get PDFMany Gram-negative bacterial pathogens such as Shigella and adhesive invasive Escherichia coli (AIEC) cause infections characteristic of hyperinflammation. These infections require antimicrobial therapy. However, due to the widespread emergence of multiple drug-resistant strains, alternative strategies must be sought to combating infectious diseases. It has been shown that natural compounds such as propolin D are able to control Shigella growth inside host cells. Geraniol is another natural product which has a chemical structure similar to the side chain of propolin D, which possesses properties potentially useful for antimicrobial therapy. qPCR analysis revealed that propolin D caused extensive bacterial envelopE stress, as indicated by a changed expression of key bacterial genes involved in stress responses. Propolin D also enhanced the autophagy activity of the host cells; the intracellular growth of S. sonnei was significantly reduced in wild type HEK293 cells but not changed in ATG5 knockout cells. Propolin D was unable to enhance septin cage as intracellular S. sonnei formed actin tails in the presence of propolin D; septin cage would restrict formation of actin tails. Geraniol has been shown to target the major virulence regulator, DsbA, which is vital for Shigella's survival in the reducing host cell cytosol. Geraniol and geranylxvacetate inhibited DsbA function in vitro; wild type DsbA efficiently reduced fluorescently labelled Di-E-GSSG whereas a mutant protein, DsbA33G, was less potent in this in vitro assay. By supplementing acidic and nutrient-poor medium with geraniol the growth of S. sonnei and AIEC strains was severely inhibited. Geraniol was effective in protecting of Galleria. mellonella larva from S. sonnei and AIEC infection. The Galleria mellonella larvae were highly tolerant to geraniol - indicating the great potential of geraniol for future in vivo and clinical studies. In light of previous reports that geraniol synergistically works with antibiotics and induces IL-10 from macrophages, it was concluded that geraniol holds great potential in treating Shigella and AIEC infections.Many Gram-negative bacterial pathogens such as Shigella and adhesive invasive Escherichia coli (AIEC) cause infections characteristic of hyperinflammation. These infections require antimicrobial therapy. However, due to the widespread emergence of multiple drug-resistant strains, alternative strategies must be sought to combating infectious diseases. It has been shown that natural compounds such as propolin D are able to control Shigella growth inside host cells. Geraniol is another natural product which has a chemical structure similar to the side chain of propolin D, which possesses properties potentially useful for antimicrobial therapy. qPCR analysis revealed that propolin D caused extensive bacterial envelopE stress, as indicated by a changed expression of key bacterial genes involved in stress responses. Propolin D also enhanced the autophagy activity of the host cells; the intracellular growth of S. sonnei was significantly reduced in wild type HEK293 cells but not changed in ATG5 knockout cells. Propolin D was unable to enhance septin cage as intracellular S. sonnei formed actin tails in the presence of propolin D; septin cage would restrict formation of actin tails. Geraniol has been shown to target the major virulence regulator, DsbA, which is vital for Shigella's survival in the reducing host cell cytosol. Geraniol and geranylxvacetate inhibited DsbA function in vitro; wild type DsbA efficiently reduced fluorescently labelled Di-E-GSSG whereas a mutant protein, DsbA33G, was less potent in this in vitro assay. By supplementing acidic and nutrient-poor medium with geraniol the growth of S. sonnei and AIEC strains was severely inhibited. Geraniol was effective in protecting of Galleria. mellonella larva from S. sonnei and AIEC infection. The Galleria mellonella larvae were highly tolerant to geraniol - indicating the great potential of geraniol for future in vivo and clinical studies. In light of previous reports that geraniol synergistically works with antibiotics and induces IL-10 from macrophages, it was concluded that geraniol holds great potential in treating Shigella and AIEC infections
Metal-free functionalisation of alkenes
Get PDFThis thesis describes two novel metal-free transformations, a method to selectively synthesise anti-diols from readily available alkene starting materials and an oxidative heterocyclisation of homoallylic nucleophiles for the synthesis of biologically significant hetereocycles.Chapter 1 describes a metal-free methodology for the preparation of anti-diols from alkenes. A selection of trans-stilbene and styrene derivatives were synthesised and reacted under optimal reaction conditions to give anti-diols in good to excellent yields and selectivities. Substituted indene and naphthalene starting materials were also prepared providing significantly better syn:anti diastereoselectivities.Chapter 2 demonstrates a novel oxidative heterocyclisation under metal-free conditions for the preparation of oxygenated heterocycles, a class of compounds with potential biological applications. For this reason, Citalopram, an antidepressant, was synthesised using this approach. This transformation provided access to γ-lactone, tetrahydrofuran and isobenzofuranone scaffolds in high levels of diastereoselectivity. Chapter 3 represents a new methodology for the intramolecular aminohydroxylation of alkenes from protected homoallylic amines in the presence of a malonoyl peroxide. This transformation was also applied to N-protected cinnamylhydroxylamines for the generation of isoxazolidines. Chapter 4 describes the experimental procedures and analytical data generated for all the compounds synthesised. Chapters 5 and 6 contain the appendix and bibliography sections of the thesis.This thesis describes two novel metal-free transformations, a method to selectively synthesise anti-diols from readily available alkene starting materials and an oxidative heterocyclisation of homoallylic nucleophiles for the synthesis of biologically significant hetereocycles.Chapter 1 describes a metal-free methodology for the preparation of anti-diols from alkenes. A selection of trans-stilbene and styrene derivatives were synthesised and reacted under optimal reaction conditions to give anti-diols in good to excellent yields and selectivities. Substituted indene and naphthalene starting materials were also prepared providing significantly better syn:anti diastereoselectivities.Chapter 2 demonstrates a novel oxidative heterocyclisation under metal-free conditions for the preparation of oxygenated heterocycles, a class of compounds with potential biological applications. For this reason, Citalopram, an antidepressant, was synthesised using this approach. This transformation provided access to γ-lactone, tetrahydrofuran and isobenzofuranone scaffolds in high levels of diastereoselectivity. Chapter 3 represents a new methodology for the intramolecular aminohydroxylation of alkenes from protected homoallylic amines in the presence of a malonoyl peroxide. This transformation was also applied to N-protected cinnamylhydroxylamines for the generation of isoxazolidines. Chapter 4 describes the experimental procedures and analytical data generated for all the compounds synthesised. Chapters 5 and 6 contain the appendix and bibliography sections of the thesis
Reputation interrupted : microblog eWOM brand image disruptions in a shareworthy world
Get PDFThe management and preservation of a corporate reputation is an ever-increasingly difficult proposition in today's environment where organisations' stakeholders have access to unprecedented levels of information at their fingertips. Advances in digital technologies, and microblogs such as Twitter, have influenced a massive shift in how stakeholders not only absorb information about products and services, but also how quickly they share their experiences of organisations with others. Managing and maintaining a consistent corporate reputation for today's stakeholder has thus become an increasingly difficult challenge for organisations.Although the power of social network site users has been highlighted extensively within the literature, there is a surprising dearth with regard to the impact that shared positive and negative brand experiences within microblogs could potentially have on receivers. For example, it is not known whether any change of perception of an organisation's reputation takes place once receivers have been exposed to a positive or negative brand experience within microblogs such as Twitter - termed Microblog Electronic Word-of-Mouth (MeWOM) brand image disruptions in this thesis. MeWOM brand image disruptions have been defined as eWOM in a microblog that either positively promotes the course, progress or transmission of a brand's image, or eWOM in a microblog that interrupts the course, progress, or transmission of a brand's image. Further, upon exposure to MeWOM brand image disruptions, the factors that influence a change in reputation remain unclear. It is important that we expand our knowledge and understanding and explore the potential risk that microblog users pose to reputations and the factors that could influence a change in a corporate reputation upon exposure to a MeWOM brand image disruption.The overall purpose of this study is to further existing empirical knowledge of the concepts of corporate image and corporate reputation in today's microblog landscape.;To achieve the objectives of this study, two phases of research were involved. Phase 1 comprised an exploratory qualitative study where 10 practitioners from various industries of type and size were interviewed. Phase 2 involved a two-stage explanatory study comprised of a quantitative study followed by a qualitative follow-up study. The quantitative study was comprised of an experiment where 372 Twitter users in the United States were exposed to positive and negative Twitter posts about airlines in an experiment setting. The experiment was designed to examine whether MeWOM brand image disruptions in Twitter had any impact on the participants' perceptions of the airlines' corporate reputations and the variables that influenced a change in corporate reputation if one took place. Partial Least Squares Structural Equation Modelling was employed to demonstrate the variables that predicted a change in corporate reputation from the receivers' perspective. Stage two of the explanatory study was a qualitative study involving 14 participants who took part in 14 semi-structured interviews. This phase of the study focused on the provision of explanatory data for the significant variables found in the quantitative phase of the study.For the academic community, this research furthers existing understanding and knowledge of the theoretical concepts of corporate image and corporate reputation and provides new empirical data to enhance theoretical assertions made within the literature. For practitioners, the findings from this project deepen the understanding of receivers of MeWOM brand image disruptions and the factors that predict a change in corporate reputation upon exposure to a MeWOM brand image disruption.The management and preservation of a corporate reputation is an ever-increasingly difficult proposition in today's environment where organisations' stakeholders have access to unprecedented levels of information at their fingertips. Advances in digital technologies, and microblogs such as Twitter, have influenced a massive shift in how stakeholders not only absorb information about products and services, but also how quickly they share their experiences of organisations with others. Managing and maintaining a consistent corporate reputation for today's stakeholder has thus become an increasingly difficult challenge for organisations.Although the power of social network site users has been highlighted extensively within the literature, there is a surprising dearth with regard to the impact that shared positive and negative brand experiences within microblogs could potentially have on receivers. For example, it is not known whether any change of perception of an organisation's reputation takes place once receivers have been exposed to a positive or negative brand experience within microblogs such as Twitter - termed Microblog Electronic Word-of-Mouth (MeWOM) brand image disruptions in this thesis. MeWOM brand image disruptions have been defined as eWOM in a microblog that either positively promotes the course, progress or transmission of a brand's image, or eWOM in a microblog that interrupts the course, progress, or transmission of a brand's image. Further, upon exposure to MeWOM brand image disruptions, the factors that influence a change in reputation remain unclear. It is important that we expand our knowledge and understanding and explore the potential risk that microblog users pose to reputations and the factors that could influence a change in a corporate reputation upon exposure to a MeWOM brand image disruption.The overall purpose of this study is to further existing empirical knowledge of the concepts of corporate image and corporate reputation in today's microblog landscape.;To achieve the objectives of this study, two phases of research were involved. Phase 1 comprised an exploratory qualitative study where 10 practitioners from various industries of type and size were interviewed. Phase 2 involved a two-stage explanatory study comprised of a quantitative study followed by a qualitative follow-up study. The quantitative study was comprised of an experiment where 372 Twitter users in the United States were exposed to positive and negative Twitter posts about airlines in an experiment setting. The experiment was designed to examine whether MeWOM brand image disruptions in Twitter had any impact on the participants' perceptions of the airlines' corporate reputations and the variables that influenced a change in corporate reputation if one took place. Partial Least Squares Structural Equation Modelling was employed to demonstrate the variables that predicted a change in corporate reputation from the receivers' perspective. Stage two of the explanatory study was a qualitative study involving 14 participants who took part in 14 semi-structured interviews. This phase of the study focused on the provision of explanatory data for the significant variables found in the quantitative phase of the study.For the academic community, this research furthers existing understanding and knowledge of the theoretical concepts of corporate image and corporate reputation and provides new empirical data to enhance theoretical assertions made within the literature. For practitioners, the findings from this project deepen the understanding of receivers of MeWOM brand image disruptions and the factors that predict a change in corporate reputation upon exposure to a MeWOM brand image disruption
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