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Plasmonic metal nanoparticles : synthesis and applications
Get PDFPreviously restricted to Strathclyde users from 1 June 2017 until 1 June 2022Plasmonic metal nanoparticles are widely exploited in academia and industry for use in various assay types. In collaboration with an industrial partner, BBI Solutions, the work here details investigations into the production and use of the plasmonic nanoparticles. The work was split into two themes. The first of these was flow chemistry of nanoparticles, covering a microfluidic assay platform and continuous colloid production.;In chapter one, a novel microfluidic assay platform was developed which facilitated the transfer of multiple, sequential bench-top procedures into a single device. This allowed the rapid detection of a sugar binding protein to be demonstrated. The microfluidic system included all pre-detection steps involved in employing the specific aggregation of functionalised silver nanoparticles. Straightforward detection of the protein was demonstrated at concentrations lower than those achieved using comparable methods in the literature.;In the second chapter, a novel bench-top scale continuous reactor for the production of gold nanoparticles was developed. It was found that the continuous stirred tank reactor was generally unsuitable for this synthesis. A laminar tubular reactor was more successful but fouling of the reactor material was a significant obstacle to production of good quality colloid. In both cases, nanoparticles produced in a batch synthesis were of more consistent quality. This suggested that further work was needed to develop a competitive continuous production method.;The second research theme was development of a novel nanoparticle assembly assay, based on DNA assembly. In chapter three it was found that current tools for the understanding of dynamic DNA structure were limited. This led to the first use of an existing coarse grain model to determine thermodynamic properties of DNA assembly. Analysis showed that the results were comparable with the best simulation models shown in the literature, while being generated much more quickly and at less computational expense.Plasmonic metal nanoparticles are widely exploited in academia and industry for use in various assay types. In collaboration with an industrial partner, BBI Solutions, the work here details investigations into the production and use of the plasmonic nanoparticles. The work was split into two themes. The first of these was flow chemistry of nanoparticles, covering a microfluidic assay platform and continuous colloid production.;In chapter one, a novel microfluidic assay platform was developed which facilitated the transfer of multiple, sequential bench-top procedures into a single device. This allowed the rapid detection of a sugar binding protein to be demonstrated. The microfluidic system included all pre-detection steps involved in employing the specific aggregation of functionalised silver nanoparticles. Straightforward detection of the protein was demonstrated at concentrations lower than those achieved using comparable methods in the literature.;In the second chapter, a novel bench-top scale continuous reactor for the production of gold nanoparticles was developed. It was found that the continuous stirred tank reactor was generally unsuitable for this synthesis. A laminar tubular reactor was more successful but fouling of the reactor material was a significant obstacle to production of good quality colloid. In both cases, nanoparticles produced in a batch synthesis were of more consistent quality. This suggested that further work was needed to develop a competitive continuous production method.;The second research theme was development of a novel nanoparticle assembly assay, based on DNA assembly. In chapter three it was found that current tools for the understanding of dynamic DNA structure were limited. This led to the first use of an existing coarse grain model to determine thermodynamic properties of DNA assembly. Analysis showed that the results were comparable with the best simulation models shown in the literature, while being generated much more quickly and at less computational expense
Development of the C-methyltransferases NovO and CouO for biocatalytic Friedel-Crafts alkylation
Get PDFThis thesis was previously held under moratorium in Chemistry Department (GSK) from 2 July 2017 until 24 May 2019, and was then restricted to Strathclyde users only until 1 August 2022.Regiospecific monoalkylation and fluoroalkylation of aromatic compounds is of key importance in medicinal chemistry, yet can be difficult to accomplish chemically. Enzymatic methods may offer a viable alternative to traditional C-C bond forming reactions, such as the Friedel-Crafts alkylation. This thesis describes a number of key advances in the use of two S-adenosyl-L-methionine (SAM) dependent methyltransferases (MTs) NovO (Streptomyces spheroides) and CouO (Streptomyces rishiriensis) as biocatalysts for the Friedel-Crafts alkylation. Firstly, NovO was expressed, purified and crystallised and the X-ray crystal structure of SelMet-NovO was solved to 1.9 Å resolution (PDB accession code: 5MGZ). Additionally, a homology model of CouO (85% sequence identity to NovO) was generated using the NovO structure. Both NovO and CouO are Class I MTs, comprising a Rossmann fold with additional α-helices at the C- and N-termini. Secondly, a catalytic mechanism for NovO was proposed based on the X-ray crystal structure, substrate docking studies, kinetic isotope effect (KIE) data and mutational analysis. This work identified a His-Arg motif to be central to the catalytic mechanism, with initial deprotonation by H120 and stabilisation of the resulting intermediate by R121. Additionally, the KIE data showed that methyl transfer was the rate limiting step. Finally, comparison with CouO identified position 117 in both proteins to be key for mediating the substrate scope of both enzymes. A third major contribution towards the development of NovO and CouO as biocatalysts was preliminary work on their directed evolution (DE) towards a wider substrate scope. Although a more efficient screening or selection strategy will be necessary to increase the substrate scope further, one mutant of NovO (N117M) was identified with higher activity toward 1, 6-dihydroxynaphthalene relative to the WT enzyme, serving as proof of concept for the 'evolvability' of these MTs. The development of a platform for biocatalytic fluoroalkylation using MTs was also explored, with extensive attempts towards the synthesis of a suitable fluoroalkylated cofactor, including the synthesis of novel fluorinated amino acids. A final key contribution towards the development of a biocatalytic Friedel-Crafts alkylation platform was the development of an in situ cofactor synthesis system using the halogenase Sa1L (Salinospora tropica). This was demonstrated on a preparative scale using crude cell lysates (methyl transfer) or purified enzymes (CD3, 13CH3, 13CD3 and Et transfer). This work addressed the issue of cofactor cost and instability associated with SAM dependent MTs.Regiospecific monoalkylation and fluoroalkylation of aromatic compounds is of key importance in medicinal chemistry, yet can be difficult to accomplish chemically. Enzymatic methods may offer a viable alternative to traditional C-C bond forming reactions, such as the Friedel-Crafts alkylation. This thesis describes a number of key advances in the use of two S-adenosyl-L-methionine (SAM) dependent methyltransferases (MTs) NovO (Streptomyces spheroides) and CouO (Streptomyces rishiriensis) as biocatalysts for the Friedel-Crafts alkylation. Firstly, NovO was expressed, purified and crystallised and the X-ray crystal structure of SelMet-NovO was solved to 1.9 Å resolution (PDB accession code: 5MGZ). Additionally, a homology model of CouO (85% sequence identity to NovO) was generated using the NovO structure. Both NovO and CouO are Class I MTs, comprising a Rossmann fold with additional α-helices at the C- and N-termini. Secondly, a catalytic mechanism for NovO was proposed based on the X-ray crystal structure, substrate docking studies, kinetic isotope effect (KIE) data and mutational analysis. This work identified a His-Arg motif to be central to the catalytic mechanism, with initial deprotonation by H120 and stabilisation of the resulting intermediate by R121. Additionally, the KIE data showed that methyl transfer was the rate limiting step. Finally, comparison with CouO identified position 117 in both proteins to be key for mediating the substrate scope of both enzymes. A third major contribution towards the development of NovO and CouO as biocatalysts was preliminary work on their directed evolution (DE) towards a wider substrate scope. Although a more efficient screening or selection strategy will be necessary to increase the substrate scope further, one mutant of NovO (N117M) was identified with higher activity toward 1, 6-dihydroxynaphthalene relative to the WT enzyme, serving as proof of concept for the 'evolvability' of these MTs. The development of a platform for biocatalytic fluoroalkylation using MTs was also explored, with extensive attempts towards the synthesis of a suitable fluoroalkylated cofactor, including the synthesis of novel fluorinated amino acids. A final key contribution towards the development of a biocatalytic Friedel-Crafts alkylation platform was the development of an in situ cofactor synthesis system using the halogenase Sa1L (Salinospora tropica). This was demonstrated on a preparative scale using crude cell lysates (methyl transfer) or purified enzymes (CD3, 13CH3, 13CD3 and Et transfer). This work addressed the issue of cofactor cost and instability associated with SAM dependent MTs
From the land of Genesis : deploying short story form to explore the fictionalization of narratives from veterans returning home
Get PDF"PhD in Creative Writing" - title page.Previously held under moratorium from 5th October 2017 until 5th October 2022.Shortly after I began interviewing combat veterans from the Iraq and Afghanistan Wars, I sent a preliminary draft of what was to become “The Parts” to a friend of mine. He’d been supportive of my writing and had often expressed admiration for the craft, so I considered him a kind of sounding board. When John handed the story back a week later, I could sense his hesitation. “It was good,” he said. But when I pressed for something more concrete, anything that I could turn constructive, he said this: “The parts about war felt like you were trying too hard. They didn’t feel authentic.” The sections that John singled out as seeming inauthentic, however, were taken almost verbatim from interviews I’d conducted. They were, if anything, the most authentic depictions of war I’d written thus far, so you can imagine my dismay. “You’re wrong,” I wanted to say. “You don’t know what you’re talking about.” The reality, however, is that John’s skepticism was grounded by a very basic observation. He knew that I’d never fought in a war. More importantly, though, I knew that I’d never fought in a war before. I was trying too hard. I was overcompensating for my lack of authority and consequently riddling my prose with so many details from source materials and interviews that the underlying narrative was all but indecipherable. Several years later, my writing managed to evolve from a set of stories that took place within the context of war to a collection that tells a diverse but connected narrative about soldiers returning from war. While the interviews I conducted served as a root for references to the Iraq and Afghanistan War experience, each of my stories assumes its own, independent authority. This is in part due to my grounding each piece within a civilian context, but it is also due to my exploration of a subject that has been only superficially explored in regards to contemporary wars: the story of our soldiers returning home, their struggles and isolation in the face of reassimilating to civilian life. It’s easy now to shrug off my encounter with John as inconsequential—as one person’s opinion of my writing at its most nascent state—but the personal concerns that he expressed over the authenticity of my collection helped to expose how contested and problematic the notion of authenticity is within the scope of contemporary war fiction. Years afterward, this realization would help prompt the questions behind this essay: namely, 1.) whether civilian authors can assume authority over the subject of contemporary wars and 2.) if possible, how an authentic rendering of war can be achieved through research and the deployment of innovative form.Shortly after I began interviewing combat veterans from the Iraq and Afghanistan Wars, I sent a preliminary draft of what was to become “The Parts” to a friend of mine. He’d been supportive of my writing and had often expressed admiration for the craft, so I considered him a kind of sounding board. When John handed the story back a week later, I could sense his hesitation. “It was good,” he said. But when I pressed for something more concrete, anything that I could turn constructive, he said this: “The parts about war felt like you were trying too hard. They didn’t feel authentic.” The sections that John singled out as seeming inauthentic, however, were taken almost verbatim from interviews I’d conducted. They were, if anything, the most authentic depictions of war I’d written thus far, so you can imagine my dismay. “You’re wrong,” I wanted to say. “You don’t know what you’re talking about.” The reality, however, is that John’s skepticism was grounded by a very basic observation. He knew that I’d never fought in a war. More importantly, though, I knew that I’d never fought in a war before. I was trying too hard. I was overcompensating for my lack of authority and consequently riddling my prose with so many details from source materials and interviews that the underlying narrative was all but indecipherable. Several years later, my writing managed to evolve from a set of stories that took place within the context of war to a collection that tells a diverse but connected narrative about soldiers returning from war. While the interviews I conducted served as a root for references to the Iraq and Afghanistan War experience, each of my stories assumes its own, independent authority. This is in part due to my grounding each piece within a civilian context, but it is also due to my exploration of a subject that has been only superficially explored in regards to contemporary wars: the story of our soldiers returning home, their struggles and isolation in the face of reassimilating to civilian life. It’s easy now to shrug off my encounter with John as inconsequential—as one person’s opinion of my writing at its most nascent state—but the personal concerns that he expressed over the authenticity of my collection helped to expose how contested and problematic the notion of authenticity is within the scope of contemporary war fiction. Years afterward, this realization would help prompt the questions behind this essay: namely, 1.) whether civilian authors can assume authority over the subject of contemporary wars and 2.) if possible, how an authentic rendering of war can be achieved through research and the deployment of innovative form
Real-time, high-throughput assessment of nanoparticle interactions with single-cells using microfluidics : applications in vaccine development
Get PDFNanomaterials are increasingly being developed for applications in biotechnology, including the delivery of therapeutic drugs and vaccine antigens. However, there is a lack of screening systems that can rapidly assess nanoparticle uptake and their consequential effects on cells. Established analytical in vitro approaches are often carried out on single time points, rely on time-consuming bulk measurements and are based primarily on populations of immortalised cell lines. As such, these procedures provide averaged results, do not guarantee precise control over the delivery of nanoparticles to cells and cannot easily generate information about the dynamic nature of nanoparticle-cell interactions and/or nanoparticle-mediated compound delivery. The present work addresses these issues by combining microfluidics, nanotechnology and imaging techniques into a high-throughput microfluidic platform to monitor nanoparticle uptake and intracellular processing in real-time and at the single-cell level. For this, a microfluidic device and protocols for cell trapping and live-cell monitoring were developed. In parallel, specific formulations of gold nanorods were produced, tested and optimised for intracellular multimodal imaging. Subsequently, controlled nanorod delivery to cells trapped in the microfluidic array was achieved across a range of concentrations, with intracellular nanorod signal detected using both fluorescence microscopy and surface-enhanced Raman scattering spectroscopy. Furthermore, on-chip measurement of specific cellular responses to nanorod delivery was also demonstrated. As a proof-of-concept application, the potential of the developed platform for understanding nanovaccine delivery and processing was investigated. Controlled delivery of ovalbumin-conjugated gold nanorods to primary dendritic cells was demonstrated, followed by real-time monitoring of nanoparticle uptake and antigen processing across a range of concentrations over several hours on hundreds of single-cells. This system represents a novel application of single-cell microfluidics for nanomaterial screening, providing a general platform for studying the dynamics of cell-nanomaterial interactions and representing a cost-saving and time-effective screening tool for many nanomaterial formulations and cell types.Nanomaterials are increasingly being developed for applications in biotechnology, including the delivery of therapeutic drugs and vaccine antigens. However, there is a lack of screening systems that can rapidly assess nanoparticle uptake and their consequential effects on cells. Established analytical in vitro approaches are often carried out on single time points, rely on time-consuming bulk measurements and are based primarily on populations of immortalised cell lines. As such, these procedures provide averaged results, do not guarantee precise control over the delivery of nanoparticles to cells and cannot easily generate information about the dynamic nature of nanoparticle-cell interactions and/or nanoparticle-mediated compound delivery. The present work addresses these issues by combining microfluidics, nanotechnology and imaging techniques into a high-throughput microfluidic platform to monitor nanoparticle uptake and intracellular processing in real-time and at the single-cell level. For this, a microfluidic device and protocols for cell trapping and live-cell monitoring were developed. In parallel, specific formulations of gold nanorods were produced, tested and optimised for intracellular multimodal imaging. Subsequently, controlled nanorod delivery to cells trapped in the microfluidic array was achieved across a range of concentrations, with intracellular nanorod signal detected using both fluorescence microscopy and surface-enhanced Raman scattering spectroscopy. Furthermore, on-chip measurement of specific cellular responses to nanorod delivery was also demonstrated. As a proof-of-concept application, the potential of the developed platform for understanding nanovaccine delivery and processing was investigated. Controlled delivery of ovalbumin-conjugated gold nanorods to primary dendritic cells was demonstrated, followed by real-time monitoring of nanoparticle uptake and antigen processing across a range of concentrations over several hours on hundreds of single-cells. This system represents a novel application of single-cell microfluidics for nanomaterial screening, providing a general platform for studying the dynamics of cell-nanomaterial interactions and representing a cost-saving and time-effective screening tool for many nanomaterial formulations and cell types
Modelling the impact of environmental change on the physiology and ecology of sandeels
Get PDFSandeels comprise a quarter of North Sea fish biomass and are vital prey for a number of marine mammals and birds. However, in recent decades there have been significant declines in sandeel abundance and energy value. These declines have been linked to climate change, however, it is unclear what the relative influence of changes in food and temperature is. Here we examine the role of these factors on different aspects of the sandeel lifecycle and determine how robust sandeels are to expected climate warming. First, we review the evidence for climate impacts on sandeels and discuss the implications for higher trophic levels with particular reference to seabirds. Evidence summarised demonstrates that sandeels are a critical food source for many seabirds, and that declines in sandeel populations have negatively impacted seabird breeding populations. Lack of existing quantitative understanding of the influence of food and temperature on sandeels demonstrates the need for a new mathematical model to predict the outcome of climate warming on sandeel stocks. Second, we model changes in spawning and hatch dates off the Scottish east coast, which have been proposed as a contributor to the long-term decline in sandeel energy content. Results indicate that spawning and hatch dates do not explain this decline. Instead, the timing of both lifecycle events is relatively fixed and is governed by predictable environmental cues. Moreover, given the weak temperature effect on spawning and hatching, future temperature rises appear unlikely to significantly affect hatch date. The central part of this thesis is the development and use of a new dynamic energy budget model to unravel the influence of food and temperature on sandeel abundance and energy content. An important application of the model was the examination of mortality rates between 2001 and 2007, a period of pronounced stock decline off the Scottish east coast. The model was driven by food and temperature. Support was found for the hypothesis that overwinter starvation mortality contributed towards a recent decline in sandeels in northern UK waters. Highest over-winter mortality rates were recorded for juveniles and not individuals aged 1 or over due to the effect of weight-specific metabolism. However, a sensitivity analysis of the model suggests that mortality rates are more sensitive to changes in copepod abundance in the build up to overwintering rather than temperature during overwintering. We suggest that food-driven size-selective starvation mortality may have contributed to the stock decline off the Scottish east coast. We therefore conclude that indirect food web effects of climate change are likely to be greater than direct physiological effects on sandeels.Sandeels comprise a quarter of North Sea fish biomass and are vital prey for a number of marine mammals and birds. However, in recent decades there have been significant declines in sandeel abundance and energy value. These declines have been linked to climate change, however, it is unclear what the relative influence of changes in food and temperature is. Here we examine the role of these factors on different aspects of the sandeel lifecycle and determine how robust sandeels are to expected climate warming. First, we review the evidence for climate impacts on sandeels and discuss the implications for higher trophic levels with particular reference to seabirds. Evidence summarised demonstrates that sandeels are a critical food source for many seabirds, and that declines in sandeel populations have negatively impacted seabird breeding populations. Lack of existing quantitative understanding of the influence of food and temperature on sandeels demonstrates the need for a new mathematical model to predict the outcome of climate warming on sandeel stocks. Second, we model changes in spawning and hatch dates off the Scottish east coast, which have been proposed as a contributor to the long-term decline in sandeel energy content. Results indicate that spawning and hatch dates do not explain this decline. Instead, the timing of both lifecycle events is relatively fixed and is governed by predictable environmental cues. Moreover, given the weak temperature effect on spawning and hatching, future temperature rises appear unlikely to significantly affect hatch date. The central part of this thesis is the development and use of a new dynamic energy budget model to unravel the influence of food and temperature on sandeel abundance and energy content. An important application of the model was the examination of mortality rates between 2001 and 2007, a period of pronounced stock decline off the Scottish east coast. The model was driven by food and temperature. Support was found for the hypothesis that overwinter starvation mortality contributed towards a recent decline in sandeels in northern UK waters. Highest over-winter mortality rates were recorded for juveniles and not individuals aged 1 or over due to the effect of weight-specific metabolism. However, a sensitivity analysis of the model suggests that mortality rates are more sensitive to changes in copepod abundance in the build up to overwintering rather than temperature during overwintering. We suggest that food-driven size-selective starvation mortality may have contributed to the stock decline off the Scottish east coast. We therefore conclude that indirect food web effects of climate change are likely to be greater than direct physiological effects on sandeels
Monitoring of fermentation processes using novel on-line techniques
Get PDFBiotechnology processes are crucial to the pharmaceutical and many other industries including the oil industry. These processes are often complex and poorly understood and hence frequently developed and operated sub-optimally. There are many techniques that could be used to monitor and improve these processes including infrared spectroscopy, acoustic monitoring and refractive index measurements. Novel probes have been designed by Bioinnovel and Stratophase that have the potential to monitor these processes using these techniques. This work investigates these new probes to monitor Xanthomonas campestris and Escherichia coli fermentations and the use of infrared to monitor a X. campestris fermentation which has not previously been studied.From the work investigating the use of infrared monitoring of a X. campestris fermentation it was shown to be possible to model the fermentation using a combination of off-line reference analyses. Mid-infrared off-line monitoring produced a PLS model which could monitor the glucose consumption within the fermenter using the 980 -1200 cm-1 region. The root mean squared error of calibration (RMSEC) of this model was 2.78 g/L over a measured glucose concentration range of 0-35 g/L. A model was also built to monitor the xanthan production of these fermentations using the same region. The RMSEC of this model was 2.78 g/L over a measured glucose concentration range of 0-25 g/L. The error associated with these models are higher than desired because of poor reference analysis as well as difficulties of the overlapping peaks of xanthan and glucose in this region.The Bioinnovel acoustic monitoring probe was first characterised to identify the optimal experimental conditions. Model analyte solutions of agar, starch, glycerol and xanthan were analysed and a relationship between the concentration of the solution and the velocity of the acoustic wave was identified. These velocities were in good agreement with the literature for example pure glycerol's measured velocity was 1914 ms-1 (Std. dev 2.19 ms-1) in comparison to the literature value of 1904 ms-1. To explore potential combination of acoustic and rheological properties, the rheological characterisation of model xanthan was carried out including viscosity measurements of 0-2% wt./v xanthan solutions. The viscosity of the solutions increases as the concentration increases therefore it may be possible in the future to combine velocity measurements with the viscosity measurements with further experiments. Throughout the experiments with the Bioinnovel probe potential improvements for the probe design were noted.The refractive index probe designed by Stratophase was used to monitor an E. coli fermentation. First the probe was characterised and off-line analysis demonstrated the potential to monitor certain analytes within the fermentation broth such as glucose and biomass. These experiments found the Bragg wavelength shift increased as the concentration of the analytes increased for example the wavelength shift of 2.5 g/L was measured as 5.50 pm and of 15 g/L was measured as 73.41 pm. When the probe was used to analyse the fermentation samples off-line the combination of the changes in the Bragg wavelength (decrease of 66 pm over 12 hours) were as expected after the model solution analysis, the decrease of the glucose concentration playing the largest part in the change in Bragg wavelength. However, on-line analysis proved difficult as the probe fouled due to biomass on the sensor window and the probe itself did not always survive the autoclaving process due to the high temperature and pressure conditions.Biotechnology processes are crucial to the pharmaceutical and many other industries including the oil industry. These processes are often complex and poorly understood and hence frequently developed and operated sub-optimally. There are many techniques that could be used to monitor and improve these processes including infrared spectroscopy, acoustic monitoring and refractive index measurements. Novel probes have been designed by Bioinnovel and Stratophase that have the potential to monitor these processes using these techniques. This work investigates these new probes to monitor Xanthomonas campestris and Escherichia coli fermentations and the use of infrared to monitor a X. campestris fermentation which has not previously been studied.From the work investigating the use of infrared monitoring of a X. campestris fermentation it was shown to be possible to model the fermentation using a combination of off-line reference analyses. Mid-infrared off-line monitoring produced a PLS model which could monitor the glucose consumption within the fermenter using the 980 -1200 cm-1 region. The root mean squared error of calibration (RMSEC) of this model was 2.78 g/L over a measured glucose concentration range of 0-35 g/L. A model was also built to monitor the xanthan production of these fermentations using the same region. The RMSEC of this model was 2.78 g/L over a measured glucose concentration range of 0-25 g/L. The error associated with these models are higher than desired because of poor reference analysis as well as difficulties of the overlapping peaks of xanthan and glucose in this region.The Bioinnovel acoustic monitoring probe was first characterised to identify the optimal experimental conditions. Model analyte solutions of agar, starch, glycerol and xanthan were analysed and a relationship between the concentration of the solution and the velocity of the acoustic wave was identified. These velocities were in good agreement with the literature for example pure glycerol's measured velocity was 1914 ms-1 (Std. dev 2.19 ms-1) in comparison to the literature value of 1904 ms-1. To explore potential combination of acoustic and rheological properties, the rheological characterisation of model xanthan was carried out including viscosity measurements of 0-2% wt./v xanthan solutions. The viscosity of the solutions increases as the concentration increases therefore it may be possible in the future to combine velocity measurements with the viscosity measurements with further experiments. Throughout the experiments with the Bioinnovel probe potential improvements for the probe design were noted.The refractive index probe designed by Stratophase was used to monitor an E. coli fermentation. First the probe was characterised and off-line analysis demonstrated the potential to monitor certain analytes within the fermentation broth such as glucose and biomass. These experiments found the Bragg wavelength shift increased as the concentration of the analytes increased for example the wavelength shift of 2.5 g/L was measured as 5.50 pm and of 15 g/L was measured as 73.41 pm. When the probe was used to analyse the fermentation samples off-line the combination of the changes in the Bragg wavelength (decrease of 66 pm over 12 hours) were as expected after the model solution analysis, the decrease of the glucose concentration playing the largest part in the change in Bragg wavelength. However, on-line analysis proved difficult as the probe fouled due to biomass on the sensor window and the probe itself did not always survive the autoclaving process due to the high temperature and pressure conditions
Strategic human resource development maturity : an investigation into Greek banks at the time of the economic crisis
Get PDFAlthough there is a consensus that Strategic Human Resource Development (SHRD) can play an important role within organisations, the ways in which it is operationalised during periods of business and economic uncertainty and complexity remains under-researched. This research explores the adoption and maturity of SHRD in Greek banks within the challenging context of the economic crisis. It examines how SHRD is perceived and operationalised within both financial institutions through the respective lenses of different HRD stakeholders. It further identifies the factors that can constrain or facilitate the adoption and maturity of SHRD in organisations. A modified SHRD framework (with its set of strategic characteristics) is proposed so to assess and evaluate SHRD maturity in both organisations. The study draws upon qualitative research data from two case studies, reporting on 76 semi-structured interviews with HR staff, branch managers and front-line employees, complemented by documentary analysis. Research data was interpreted through a pre and post-crisis assessment so to allow for an in-depth investigation into people's perspectives on the understanding and maturity of SHRD over time. Research evidence highlights the complexity being attached to stakeholders' understanding of SHRD, with their perceptual contradiction to be noticed. There is also mixed evidence on the employment of the strategic criteria, and of their respective indicators, in both cases. However, a striking observation suggests HRD practices being proved "environmentally-integrated" (fully aligned with new business objectives, besides their short-term orientation) in terms of their responsiveness to the constantly changing business environments. Finally, economic crisis has been identified as the major impeding factor of SHRD, with other factors to follow. The thesis' original contribution derives from applying a modified SHRD framework within the challenging context of an economic crisis (thus addressing previous models' limitation of being assessed within "static" business and economic environments). The study also advances qualitative research through its adopted methodological approach (case study research strategy, before-and-after research design, multi-constituent research perspective). Finally, it contributes to SHRD literature by extending a large amount of knowledge within a different/specific industrial and national context.Although there is a consensus that Strategic Human Resource Development (SHRD) can play an important role within organisations, the ways in which it is operationalised during periods of business and economic uncertainty and complexity remains under-researched. This research explores the adoption and maturity of SHRD in Greek banks within the challenging context of the economic crisis. It examines how SHRD is perceived and operationalised within both financial institutions through the respective lenses of different HRD stakeholders. It further identifies the factors that can constrain or facilitate the adoption and maturity of SHRD in organisations. A modified SHRD framework (with its set of strategic characteristics) is proposed so to assess and evaluate SHRD maturity in both organisations. The study draws upon qualitative research data from two case studies, reporting on 76 semi-structured interviews with HR staff, branch managers and front-line employees, complemented by documentary analysis. Research data was interpreted through a pre and post-crisis assessment so to allow for an in-depth investigation into people's perspectives on the understanding and maturity of SHRD over time. Research evidence highlights the complexity being attached to stakeholders' understanding of SHRD, with their perceptual contradiction to be noticed. There is also mixed evidence on the employment of the strategic criteria, and of their respective indicators, in both cases. However, a striking observation suggests HRD practices being proved "environmentally-integrated" (fully aligned with new business objectives, besides their short-term orientation) in terms of their responsiveness to the constantly changing business environments. Finally, economic crisis has been identified as the major impeding factor of SHRD, with other factors to follow. The thesis' original contribution derives from applying a modified SHRD framework within the challenging context of an economic crisis (thus addressing previous models' limitation of being assessed within "static" business and economic environments). The study also advances qualitative research through its adopted methodological approach (case study research strategy, before-and-after research design, multi-constituent research perspective). Finally, it contributes to SHRD literature by extending a large amount of knowledge within a different/specific industrial and national context
Internet crowdsourcing for generative design
Get PDFIn recent years, the ''power of the crowd" has been repeatedly demonstrated and various Internet platforms have been used to support applications of collaborative intelligence in tasks ranging from open innovation to image analysis. However, crowdsourcing applications in the fields of design research and creative innovation have been much slower to emerge. So, although there have been reports of systems and researchers using Internet crowdsourcing to carry out generative design, there are still many gaps in knowledge about the capability and limitations of the technology. Indeed the process models developed to support traditional commercial design (e.g. Pugh's Total Design, Agile, Double-Diamond etc.) have yet to be established for Crowdsourced Design (cDesign). As a contribution to the development of such a general model this thesis proposes the cDesign framework to support the effective use [sic] crowdsourcing for generative design. Within the cDesign framework the effective evaluation of design quality is identified as a key component that not only enables the leveraging of a large, virtual workforce's creative activities but is also fundamental to almost all iterative optimisation processes. This thesis first describes a brief history of the internet crowdsourcing and how crowdsourcing has been used in the design domain. Then the aims and objectives of this research work are listed which are followed by the methodologies chosen for the research. After that three crowdsourced design case studies are presented and discussed. The results of these case studies are integrated to establish the cDesign framework. A fourth crowdsourced design case study on the validation of this cDesign framework is described before a final discussion on the significance of this research work presented. The thesis concludes, by identifying the limitations of the work and opportunities for future research.In recent years, the ''power of the crowd" has been repeatedly demonstrated and various Internet platforms have been used to support applications of collaborative intelligence in tasks ranging from open innovation to image analysis. However, crowdsourcing applications in the fields of design research and creative innovation have been much slower to emerge. So, although there have been reports of systems and researchers using Internet crowdsourcing to carry out generative design, there are still many gaps in knowledge about the capability and limitations of the technology. Indeed the process models developed to support traditional commercial design (e.g. Pugh's Total Design, Agile, Double-Diamond etc.) have yet to be established for Crowdsourced Design (cDesign). As a contribution to the development of such a general model this thesis proposes the cDesign framework to support the effective use [sic] crowdsourcing for generative design. Within the cDesign framework the effective evaluation of design quality is identified as a key component that not only enables the leveraging of a large, virtual workforce's creative activities but is also fundamental to almost all iterative optimisation processes. This thesis first describes a brief history of the internet crowdsourcing and how crowdsourcing has been used in the design domain. Then the aims and objectives of this research work are listed which are followed by the methodologies chosen for the research. After that three crowdsourced design case studies are presented and discussed. The results of these case studies are integrated to establish the cDesign framework. A fourth crowdsourced design case study on the validation of this cDesign framework is described before a final discussion on the significance of this research work presented. The thesis concludes, by identifying the limitations of the work and opportunities for future research
Advancing stoichiometric and catalytic applications of cooperative bimetallics in organic synthesis
Get PDFAdvancing the exploitation of alkali metal-magnesiates and alkali metal-manganates in a variety of fundamental organic transformations, this thesis presents an extensive study, which assesses synergistic behaviours in this systems and their ability to promote catalytic transformations. Using novel potassium magnesiates such as (PMDETA)2K2Mg(CH2SiMe3)4 (1b), selective magnesiation of aromatic and heterocyclic substrates has been accomplished under mild reaction conditions, using an hydrocarbon solvent. These studies have revealed an important alkali metal effect; thus when the K atom in 1b is replaced by Li or Na, the direct magnesiation processes are inhibited. The ability of sodium magnesiates to perform catalytic transformations has been disclosed, finding that higher order sodium magnesiate (TMEDA)2Na2Mg(CH2SiMe3)4 (1d) catalyses the cycloaddition of alkynes to azides with the corresponding formation of a wide range of 1,5-disubstituted-1,2,3-triazoles. Structural elucidation of key organometallic intermediates along with 1H DOSY NMR studies has revealed sodium magnesiate [(THF)4Na2Mg{C≡C(p-tolyl)}4] (1j) is a reaction intermediate in these processes. Mechanistic insights have been gained by kinetic studies which revealed that the reaction rate is zero-order in alkyne and order one in azide and catalyst, thus indicating the insertion/intramolecular nucleophilic attack is the rate determining step of the reaction. NaMg(CH2SiMe3)3 (1f) was found to perform the guanylation and hydrophosphination of multiple amines/phosphines upon reactions with carbodiimides at ambient temperature and in very short periods of time. Comprehensive stoichiometric and kinetic studies revealed this reaction takes place via tris amido sodium magnesiate (1m) and mixed amido/guanidinate (1o) intermediates. Interestingly, a concerted transition state is proposed which agrees with the first order observed in amine and carbodiimide. Lithium manganate (THF)xLi2Mn(CH2SiMe3)4 (1u) was found to be an excellent reagents for the Mn/I exchange reaction of iodoaryls followed by homocoupling for the synthesis of a variety of symmetric biaryl reagents. Interestingly the activity of 1u could be upgraded to catalytic conditions, with the use of Mg(s) as reducing agent. Preliminary mechanistic studies have revealed that Li plays a major role in this transformations.Advancing the exploitation of alkali metal-magnesiates and alkali metal-manganates in a variety of fundamental organic transformations, this thesis presents an extensive study, which assesses synergistic behaviours in this systems and their ability to promote catalytic transformations. Using novel potassium magnesiates such as (PMDETA)2K2Mg(CH2SiMe3)4 (1b), selective magnesiation of aromatic and heterocyclic substrates has been accomplished under mild reaction conditions, using an hydrocarbon solvent. These studies have revealed an important alkali metal effect; thus when the K atom in 1b is replaced by Li or Na, the direct magnesiation processes are inhibited. The ability of sodium magnesiates to perform catalytic transformations has been disclosed, finding that higher order sodium magnesiate (TMEDA)2Na2Mg(CH2SiMe3)4 (1d) catalyses the cycloaddition of alkynes to azides with the corresponding formation of a wide range of 1,5-disubstituted-1,2,3-triazoles. Structural elucidation of key organometallic intermediates along with 1H DOSY NMR studies has revealed sodium magnesiate [(THF)4Na2Mg{C≡C(p-tolyl)}4] (1j) is a reaction intermediate in these processes. Mechanistic insights have been gained by kinetic studies which revealed that the reaction rate is zero-order in alkyne and order one in azide and catalyst, thus indicating the insertion/intramolecular nucleophilic attack is the rate determining step of the reaction. NaMg(CH2SiMe3)3 (1f) was found to perform the guanylation and hydrophosphination of multiple amines/phosphines upon reactions with carbodiimides at ambient temperature and in very short periods of time. Comprehensive stoichiometric and kinetic studies revealed this reaction takes place via tris amido sodium magnesiate (1m) and mixed amido/guanidinate (1o) intermediates. Interestingly, a concerted transition state is proposed which agrees with the first order observed in amine and carbodiimide. Lithium manganate (THF)xLi2Mn(CH2SiMe3)4 (1u) was found to be an excellent reagents for the Mn/I exchange reaction of iodoaryls followed by homocoupling for the synthesis of a variety of symmetric biaryl reagents. Interestingly the activity of 1u could be upgraded to catalytic conditions, with the use of Mg(s) as reducing agent. Preliminary mechanistic studies have revealed that Li plays a major role in this transformations
Developing anomaly detection, diagnostics and prognostics for condition monitoring with limited historical data in new applications such as tidal power
Get PDFTidal power is a promising source of renewable energy worldwide, more stable and predictable than alternatives such as offshore wind power. However, the harsh operating environment makes maintenance of tidal turbines difficult and costly to perform. Intelligent condition monitoring systems, utilised as part of a condition-based maintenance strategy, can provide operators with timely and accurate indications of faults before serious damage occurs. Nevertheless, tidal technology is a new application, where deployments are currently in its infancy. Therefore, there is limited practical experience of how faults will develop within tidal turbines in operation. This thesis aims to investigate the requirements of condition monitoring methods, from both theory and knowledge of similar fields (such as offshore wind), to develop an approach for applying condition monitoring in new applications. This work first investigates the response of a commercial-scale tidal turbine in operation through a data mining analysis of condition data from the Andritz Hydro Hammerfest HS1000 tidal turbine. Data mining was performed following the CRISP-DM methodology and was used to build models of the normal condition response of turbine components, from which anomalous behaviour indicative of the development of faults can be detected. This approach was then expanded to include both diagnostic and prognostic modelling, where faults can be automatically classified and the remaining useful life of equipment undergoing degradation can be estimated. This has resulted in a generalised framework, based on CRISP-DM, that can be applied to perform condition monitoring in new applications, learning from the response of machinery over time during its operation.Tidal power is a promising source of renewable energy worldwide, more stable and predictable than alternatives such as offshore wind power. However, the harsh operating environment makes maintenance of tidal turbines difficult and costly to perform. Intelligent condition monitoring systems, utilised as part of a condition-based maintenance strategy, can provide operators with timely and accurate indications of faults before serious damage occurs. Nevertheless, tidal technology is a new application, where deployments are currently in its infancy. Therefore, there is limited practical experience of how faults will develop within tidal turbines in operation. This thesis aims to investigate the requirements of condition monitoring methods, from both theory and knowledge of similar fields (such as offshore wind), to develop an approach for applying condition monitoring in new applications. This work first investigates the response of a commercial-scale tidal turbine in operation through a data mining analysis of condition data from the Andritz Hydro Hammerfest HS1000 tidal turbine. Data mining was performed following the CRISP-DM methodology and was used to build models of the normal condition response of turbine components, from which anomalous behaviour indicative of the development of faults can be detected. This approach was then expanded to include both diagnostic and prognostic modelling, where faults can be automatically classified and the remaining useful life of equipment undergoing degradation can be estimated. This has resulted in a generalised framework, based on CRISP-DM, that can be applied to perform condition monitoring in new applications, learning from the response of machinery over time during its operation
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