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Advanced structural modelling and design of wind turbine electrical generators
Get PDFThis thesis concentrates on direct drive electrical generators for wind energy applications. A variety of wind turbine configurations and generator topologies are reviewed.;Direct drive renewable energy converters introduce a low speed, high torque input into the electrical machine. Due to this, these generators have to be larger and more robust than their high speed counterparts. With very large airgap closing forces, a very stiff structure capable of withstanding the stress is necessary. As a result very heavy machines, with structural ('inactive') material dominating the electromagnetically 'active' material are designed.;In this thesis a stiffness approach is introduced which combines electromagnetic stiffness and structural stiffness for different modes of deflection. This is used to minimise mass of the generator by trading stiffness of rotor and stator structures.;Design tools are presented, validated and utilised to model lightweight supporting structures ('inactive material') for high torque radial flux permanent magnet synchronous generators. Different structural layouts are statically studied, compared and optimised. Making use of low density materials, such as composites, a simplified generator structure is designed and contrasted with its optimised steel counterpart.;As a rotating piece machinery forming part of a bigger and more complex machine, electrical generators are subject to dynamic and external forces coming from the wind turbine rotor. The optimised steel design is looked at from a dynamic viewpoint. Discussions and conclusions highlight the potential design solutions that can be adopted to minimise the mass and therefore the cost of these machines.This thesis concentrates on direct drive electrical generators for wind energy applications. A variety of wind turbine configurations and generator topologies are reviewed.;Direct drive renewable energy converters introduce a low speed, high torque input into the electrical machine. Due to this, these generators have to be larger and more robust than their high speed counterparts. With very large airgap closing forces, a very stiff structure capable of withstanding the stress is necessary. As a result very heavy machines, with structural ('inactive') material dominating the electromagnetically 'active' material are designed.;In this thesis a stiffness approach is introduced which combines electromagnetic stiffness and structural stiffness for different modes of deflection. This is used to minimise mass of the generator by trading stiffness of rotor and stator structures.;Design tools are presented, validated and utilised to model lightweight supporting structures ('inactive material') for high torque radial flux permanent magnet synchronous generators. Different structural layouts are statically studied, compared and optimised. Making use of low density materials, such as composites, a simplified generator structure is designed and contrasted with its optimised steel counterpart.;As a rotating piece machinery forming part of a bigger and more complex machine, electrical generators are subject to dynamic and external forces coming from the wind turbine rotor. The optimised steel design is looked at from a dynamic viewpoint. Discussions and conclusions highlight the potential design solutions that can be adopted to minimise the mass and therefore the cost of these machines
Assessment of ship cargo liquefaction
Get PDFLiquefaction of fine particle cargoes such as unprocessed nickel ore and iron ore, resulting in cargo shift and loss of stability of ships, has caused the loss of many lives in marine casualties over the recent few years. Since the dangers of cargo liquefaction have long been known to the shipping industry, the question of why the phenomenon is resurfacing now would be a legitimate one.;Under the requirements of International Maritime Bulk Solid Cargoes (IMSBC) Code adopted by the Maritime Safety Committee of the Organization, the moisture content of the cargo that may liquefy shall be kept less than its Transportable Moisture Limit (TML) in advance of loading, as determined from one of three laboratory test methods specified in IMSBC code. However, the accuracy of these methods is still not understood and the TML result varies particularly when conducted in different laboratories or in different methods for a given sample (Rose, 2014).;Considering the ambiguity of testing (unavailability or non-compliance) and the variability in cargo properties and state as well as conditions that can lead to liquefaction (pertaining to ship design and operation and to environmental conditions), it is necessary to investigate the root causes that trigger the phenomenon and address the problem in a comprehensive manner.;On the other hand, despite the positive steps that have been taken towards prevention of such shipping accidents, IMSBC code appears to have certain limitations and leaves the shipper responsible to involve the competent authority and the operator for the characterization of the cargo and the hazards it entails for the ship and its crew, if in doubt. This thesis, therefore, gives consideration to the development of the numerical simulation method to the ship cargo liquefaction, which could be feasibly used as a reference and possibly support a suitable regulatory framework for the liquefaction analysis of cargoes.Liquefaction of fine particle cargoes such as unprocessed nickel ore and iron ore, resulting in cargo shift and loss of stability of ships, has caused the loss of many lives in marine casualties over the recent few years. Since the dangers of cargo liquefaction have long been known to the shipping industry, the question of why the phenomenon is resurfacing now would be a legitimate one.;Under the requirements of International Maritime Bulk Solid Cargoes (IMSBC) Code adopted by the Maritime Safety Committee of the Organization, the moisture content of the cargo that may liquefy shall be kept less than its Transportable Moisture Limit (TML) in advance of loading, as determined from one of three laboratory test methods specified in IMSBC code. However, the accuracy of these methods is still not understood and the TML result varies particularly when conducted in different laboratories or in different methods for a given sample (Rose, 2014).;Considering the ambiguity of testing (unavailability or non-compliance) and the variability in cargo properties and state as well as conditions that can lead to liquefaction (pertaining to ship design and operation and to environmental conditions), it is necessary to investigate the root causes that trigger the phenomenon and address the problem in a comprehensive manner.;On the other hand, despite the positive steps that have been taken towards prevention of such shipping accidents, IMSBC code appears to have certain limitations and leaves the shipper responsible to involve the competent authority and the operator for the characterization of the cargo and the hazards it entails for the ship and its crew, if in doubt. This thesis, therefore, gives consideration to the development of the numerical simulation method to the ship cargo liquefaction, which could be feasibly used as a reference and possibly support a suitable regulatory framework for the liquefaction analysis of cargoes
Responsive emulsifiers based on peptide self-assembly
No full textThe molecular self-assembly of aromatic peptide amphiphiles has raised interest through the last decades due to the possibility to form different nanostructures in aqueous medium, depending on the sequence, kinetics and established non-covalent interactions. Enzyme triggered self-assembly gives an extra spatiotemporal control over the assembling process when initiating, e.g., fibre formation and consequent gelation under physiological unchanged conditions. The development of natural alternative types of emulsifiers is critical and more recently sought within the cosmetic/food industries. Peptides can act as surfactants if they are designed to present an amphiphilic nature, and can also be switchable if designed to respond to stimuli, which would be attractive for different applications. An alkaline phosphatase is used to transform phosphorylated precursors into self-assembling aromatic-capped dipeptide amphiphiles, providing a route to trigger self-assembly of nanofibrous networks and hydrogels in aqueous medium. The same mechanism is proven for unprotected tripeptides, where the kinetic control, tuned by the amount of enzyme used, is shown to play a key role in dictating the morphology of the nanofibrous networks produced and consequent hydrogel stiffness. When the aromatic dipeptide amphiphiles or amphiphilic tripeptides are used in biphasic systems, nanofibrous networks are shown to self-assemble preferentially at the aqueous/organic interface or vicinity, thereby stabilising the oil-in-water droplet dispersions. Alkaline phosphatase is shown to be active in aqueous-organic solvent systems, in approximately the same extent as in aqueous buffer. Different experimental and computational techniques are used to obtain further insight on the supramolecular interactions responsible for the self-assembly process, in both aqueous and biphasics systems. The ability of on-demand emulsification is shown by the addition of the enzyme to the biphasic de-emulsified mixture after storage for different times, proving these two kinds of peptidic systems can be used as responsive emulsifiers. In addition, the possibility of controlling the emulsification extent by taking advantage of the dephosphorylation kinetics and consequent formation of different stabilising fibrous networks is shown.The use of a non-covalent trigger for the formation of a specific structure can also be attractive for various applications. The possibility of achieving innovative functional materials through co-assembly of tripeptides and dipeptides is also studied. A computational screening approach has been developed for the creation of design rules to produce hydrogelators and better emulsifiers. In this work, the possibility of on-demand emulsification when using biocatalytically-triggered self-assembly of short peptide amphiphiles was shown for the first time. The time control and tuning over the emulsifying ability extent was also proved. Additionally, design methods allow for the identification of promising candidates for numerous types of materials. Co-assembled tripeptides and dipeptides can be carefully designed to give rise to hydrogels and effective emulsifiers, which can be highly attractive for different applications.The molecular self-assembly of aromatic peptide amphiphiles has raised interest through the last decades due to the possibility to form different nanostructures in aqueous medium, depending on the sequence, kinetics and established non-covalent interactions. Enzyme triggered self-assembly gives an extra spatiotemporal control over the assembling process when initiating, e.g., fibre formation and consequent gelation under physiological unchanged conditions. The development of natural alternative types of emulsifiers is critical and more recently sought within the cosmetic/food industries. Peptides can act as surfactants if they are designed to present an amphiphilic nature, and can also be switchable if designed to respond to stimuli, which would be attractive for different applications. An alkaline phosphatase is used to transform phosphorylated precursors into self-assembling aromatic-capped dipeptide amphiphiles, providing a route to trigger self-assembly of nanofibrous networks and hydrogels in aqueous medium. The same mechanism is proven for unprotected tripeptides, where the kinetic control, tuned by the amount of enzyme used, is shown to play a key role in dictating the morphology of the nanofibrous networks produced and consequent hydrogel stiffness. When the aromatic dipeptide amphiphiles or amphiphilic tripeptides are used in biphasic systems, nanofibrous networks are shown to self-assemble preferentially at the aqueous/organic interface or vicinity, thereby stabilising the oil-in-water droplet dispersions. Alkaline phosphatase is shown to be active in aqueous-organic solvent systems, in approximately the same extent as in aqueous buffer. Different experimental and computational techniques are used to obtain further insight on the supramolecular interactions responsible for the self-assembly process, in both aqueous and biphasics systems. The ability of on-demand emulsification is shown by the addition of the enzyme to the biphasic de-emulsified mixture after storage for different times, proving these two kinds of peptidic systems can be used as responsive emulsifiers. In addition, the possibility of controlling the emulsification extent by taking advantage of the dephosphorylation kinetics and consequent formation of different stabilising fibrous networks is shown.The use of a non-covalent trigger for the formation of a specific structure can also be attractive for various applications. The possibility of achieving innovative functional materials through co-assembly of tripeptides and dipeptides is also studied. A computational screening approach has been developed for the creation of design rules to produce hydrogelators and better emulsifiers. In this work, the possibility of on-demand emulsification when using biocatalytically-triggered self-assembly of short peptide amphiphiles was shown for the first time. The time control and tuning over the emulsifying ability extent was also proved. Additionally, design methods allow for the identification of promising candidates for numerous types of materials. Co-assembled tripeptides and dipeptides can be carefully designed to give rise to hydrogels and effective emulsifiers, which can be highly attractive for different applications
Advancing alkali metal dihydropyridine chemistry : syntheses, structures and applications
Get PDFThis project develops the chemistry of Group 1 dihydropyridines, a class of compound previously largely confined to lithium. A synthetic approach to sodium and potassium derivatives has been optimised via metathesis, the new compounds have been thoroughly characterised and the catalytic ability of the family has been assessed.Firstly, the previously reported lithium dihydropyridine (LiDHP) proved a valuable precursor to access five new s-block dihydropyridines that have been isolated and characterised by X-ray crystallography and NMR spectroscopy. The isomerisations of the 1,2- to the 1,4- isomeric forms have been monitored by NMR spectroscopy.Thermal studies on the non-solvated derivatives were performed and related to their ability to release metal hydride. Their proficiency to act as metal hydride surrogates was confirmed in reactions reducing benzophenone. Secondly, the first catalytic role of LiDHPs was established in the successful catalysed dehydrogenative cyclisation of diamine boranes. It was found that the LiDHP catalyst could compete with a ruthenium catalyst to prepare desired 1,3,2-borolidines. A three-step mechanism has been suggested, (deprotonation, β-hydride elimination and intramolecular hydrogen loss) supported by crystallographically characterised intermediates and extensive NMR studies. Formed in situ, the borolidines were further functionalised to more synthetically useful phenylborane derivatives.The LiDHP was next subjected to a further catalytic screening for hydroboration of carbonyls. This also proved successful for preparing boronate esters, from a range of aldehydes and ketones with pinacolborane. The reaction was thought to proceed akin to that reported in the literature, namely a hydrometallation followed by a metathesis step. However, an acceptor-donor adduct of pyridine and pinacolborane, characterised by X-ray crystallography, provided insight to a potential alternative pathway in the catalytic cycle.Finally, expanding on the monometallic dihydropyridines, six new heterobimetallic dihydropyridine complexes, Li/Al, K/Al and K/Zn, have been synthesised andcrystallographically characterised. Their structural assembly is contrasted with similar literature complexes.This project develops the chemistry of Group 1 dihydropyridines, a class of compound previously largely confined to lithium. A synthetic approach to sodium and potassium derivatives has been optimised via metathesis, the new compounds have been thoroughly characterised and the catalytic ability of the family has been assessed.Firstly, the previously reported lithium dihydropyridine (LiDHP) proved a valuable precursor to access five new s-block dihydropyridines that have been isolated and characterised by X-ray crystallography and NMR spectroscopy. The isomerisations of the 1,2- to the 1,4- isomeric forms have been monitored by NMR spectroscopy.Thermal studies on the non-solvated derivatives were performed and related to their ability to release metal hydride. Their proficiency to act as metal hydride surrogates was confirmed in reactions reducing benzophenone. Secondly, the first catalytic role of LiDHPs was established in the successful catalysed dehydrogenative cyclisation of diamine boranes. It was found that the LiDHP catalyst could compete with a ruthenium catalyst to prepare desired 1,3,2-borolidines. A three-step mechanism has been suggested, (deprotonation, β-hydride elimination and intramolecular hydrogen loss) supported by crystallographically characterised intermediates and extensive NMR studies. Formed in situ, the borolidines were further functionalised to more synthetically useful phenylborane derivatives.The LiDHP was next subjected to a further catalytic screening for hydroboration of carbonyls. This also proved successful for preparing boronate esters, from a range of aldehydes and ketones with pinacolborane. The reaction was thought to proceed akin to that reported in the literature, namely a hydrometallation followed by a metathesis step. However, an acceptor-donor adduct of pyridine and pinacolborane, characterised by X-ray crystallography, provided insight to a potential alternative pathway in the catalytic cycle.Finally, expanding on the monometallic dihydropyridines, six new heterobimetallic dihydropyridine complexes, Li/Al, K/Al and K/Zn, have been synthesised andcrystallographically characterised. Their structural assembly is contrasted with similar literature complexes
Media representations of gender in the Scottish public sphere in the context of the 2014 independence referendum
Get PDFThis thesis was previously held under moratorium from 22/05/2018 to 01/06/2023This thesis explores the mediated representation of gender in the Scottish public sphere in the context of the Scottish independence referendum in 2014. In particular it focuses on media samples which centre on key political figures from the campaign. The study combines two corpora: articles from the Scottish press, and tweets from the social media platform Twitter. It uses a mixed methods approach combining content analysis and critical discourse analysis to explore the mediated representations of these politicians. It first looks to the patterns emerging from a large volume of data before moving on to a more detailed analysis of how language is used to construct discourses of gender. Findings show an overall conversationalisation of discourse but with more informal naming practices used for female politicians.There was also evidence of a personalisation of political figures, although in this case a higher amount of discussion focused on male leaders. Contrary to findings of comparable studies, both male and female politicians had similar proportions of mentions of their appearance overall, though this tended to focus on specific individuals. While appearance was used as a metonym for identity across both genders, this had gendered differences; in regard to men these discourses were used to criticise male dominance and “middle-aged men in suits”, while for women it was used to undermine their political competency, showing evidence of a double bind and media confusion around the terms by which women politicians should be assessed. The gender of the women was foregrounded in the media discourse more than men, which showed tensions around differentialist and egalitarian perceptions of their representation.Female politicians were presented as embodying a specific feminised style, with those that violated this represented in negatively gendered terms. Though there was evidence of contestation to male-dominated politics, discourses still reified traditional gender norms and situated women as outsiders to the political public sphere. Nonetheless, despite these resilient gendered narratives, the presence of contestation shows an expressed desire for a feminised Scottish public sphere.This thesis explores the mediated representation of gender in the Scottish public sphere in the context of the Scottish independence referendum in 2014. In particular it focuses on media samples which centre on key political figures from the campaign. The study combines two corpora: articles from the Scottish press, and tweets from the social media platform Twitter. It uses a mixed methods approach combining content analysis and critical discourse analysis to explore the mediated representations of these politicians. It first looks to the patterns emerging from a large volume of data before moving on to a more detailed analysis of how language is used to construct discourses of gender. Findings show an overall conversationalisation of discourse but with more informal naming practices used for female politicians.There was also evidence of a personalisation of political figures, although in this case a higher amount of discussion focused on male leaders. Contrary to findings of comparable studies, both male and female politicians had similar proportions of mentions of their appearance overall, though this tended to focus on specific individuals. While appearance was used as a metonym for identity across both genders, this had gendered differences; in regard to men these discourses were used to criticise male dominance and “middle-aged men in suits”, while for women it was used to undermine their political competency, showing evidence of a double bind and media confusion around the terms by which women politicians should be assessed. The gender of the women was foregrounded in the media discourse more than men, which showed tensions around differentialist and egalitarian perceptions of their representation.Female politicians were presented as embodying a specific feminised style, with those that violated this represented in negatively gendered terms. Though there was evidence of contestation to male-dominated politics, discourses still reified traditional gender norms and situated women as outsiders to the political public sphere. Nonetheless, despite these resilient gendered narratives, the presence of contestation shows an expressed desire for a feminised Scottish public sphere
Entrepreneurship and development as freedom : the case of women in rural Nepal
Get PDFIt is widely recognised that top-down, donor conditionality-driven and outside-expert-led initiatives that characterised early approaches to poverty alleviation among the world's 'bottom billion' have largely failed. A new generation of development strategies, focused on entrepreneurship and small business ownership, are increasingly used to alleviate persistent poverty. This study explores the potential for entrepreneurship to act as a real and appropriate opportunity among rural Nepali women. Using the Capability Approach (CA) to define poverty and development, the thesis presents entrepreneurship as an opportunity that enables individuals to actively shape their lives and the lives of others to realise aspirations.This research study is exploratory and adopts a qualitative research approach, drawing data from the remote Rapti Zone in Mid-West Nepal. In-depth, semi-structured interviews were conducted with nine established women entrepreneurs and seven nascent women entrepreneurs involved with an entrepreneurship enabling organisation. These were complemented by data drawn from eight local experts and a village hall meeting with 26 participants. This data collection strategy enabled the study to present a contextualised understanding of female entrepreneuring within a remote and impoverished community.The results of the study contribute to ongoing debates regarding the relationship between entrepreneurship, capabilities and poverty as capability deprivation. The study contributes to a better understanding of the emancipatory impacts of entrepreneurship; highlights the significance of context on entrepreneurial opportunity and the transformative value of entrepreneurship enabling organisations; and presents evidence to suggest that entrepreneurship (as a new opportunity) enables a departure from pre-existing constraints through the extension of gender roles. Finally, the study indicates that, through collective agency, entrepreneurship has the potential to indirectly emancipate other women and girls within their context, contributing to a true departure from the intellectual, psychological, economic, social, institutional or cultural constraints that have, over the years, inhibited the actions of Nepali women.It is widely recognised that top-down, donor conditionality-driven and outside-expert-led initiatives that characterised early approaches to poverty alleviation among the world's 'bottom billion' have largely failed. A new generation of development strategies, focused on entrepreneurship and small business ownership, are increasingly used to alleviate persistent poverty. This study explores the potential for entrepreneurship to act as a real and appropriate opportunity among rural Nepali women. Using the Capability Approach (CA) to define poverty and development, the thesis presents entrepreneurship as an opportunity that enables individuals to actively shape their lives and the lives of others to realise aspirations.This research study is exploratory and adopts a qualitative research approach, drawing data from the remote Rapti Zone in Mid-West Nepal. In-depth, semi-structured interviews were conducted with nine established women entrepreneurs and seven nascent women entrepreneurs involved with an entrepreneurship enabling organisation. These were complemented by data drawn from eight local experts and a village hall meeting with 26 participants. This data collection strategy enabled the study to present a contextualised understanding of female entrepreneuring within a remote and impoverished community.The results of the study contribute to ongoing debates regarding the relationship between entrepreneurship, capabilities and poverty as capability deprivation. The study contributes to a better understanding of the emancipatory impacts of entrepreneurship; highlights the significance of context on entrepreneurial opportunity and the transformative value of entrepreneurship enabling organisations; and presents evidence to suggest that entrepreneurship (as a new opportunity) enables a departure from pre-existing constraints through the extension of gender roles. Finally, the study indicates that, through collective agency, entrepreneurship has the potential to indirectly emancipate other women and girls within their context, contributing to a true departure from the intellectual, psychological, economic, social, institutional or cultural constraints that have, over the years, inhibited the actions of Nepali women
A wearable platform for monitoring the tissue viability of lower limb amputees
Get PDFAround the world the incidence of lower limb amputation is on the rise. These rising numbers puts a huge constraint on the health care resources, thereby making the rehabilitative process challenging for both the healthcare services as well as the amputee. People with a lower limb amputation need regular rehabilitative care as their residual limb skin is prone to infections, volume fluctuations, skin breakdown etc. e-Health wearable communication systems show promise in delivering improvements in patient care while at the same time reducing both the demand for resources and the financial burden on healthcare systems. These systems have the capability of monitoring, logging and transmitting patient data to a central health authority. This thesis investigates the design of a wearable sensor communication platform which is capable of harvesting the data from multiple sensors for in-situ monitoring of residual limb health in amputees. The monitoring of residual limb temperature and gait is done in a contactless way by utilising mathematical algorithms. The platform works with an Android mobile device, in order to allow for the capture of data from a wireless sensor unit, and to give the clinician access to results from the sensors. The results from the analysis, carried out within the secure server, are demonstrated to be of use for remote monitoring. This knowledge will be useful in establishing biomarkers related to a possible deterioration in a patient's health or for assessing the impact of clinical interventions.Around the world the incidence of lower limb amputation is on the rise. These rising numbers puts a huge constraint on the health care resources, thereby making the rehabilitative process challenging for both the healthcare services as well as the amputee. People with a lower limb amputation need regular rehabilitative care as their residual limb skin is prone to infections, volume fluctuations, skin breakdown etc. e-Health wearable communication systems show promise in delivering improvements in patient care while at the same time reducing both the demand for resources and the financial burden on healthcare systems. These systems have the capability of monitoring, logging and transmitting patient data to a central health authority. This thesis investigates the design of a wearable sensor communication platform which is capable of harvesting the data from multiple sensors for in-situ monitoring of residual limb health in amputees. The monitoring of residual limb temperature and gait is done in a contactless way by utilising mathematical algorithms. The platform works with an Android mobile device, in order to allow for the capture of data from a wireless sensor unit, and to give the clinician access to results from the sensors. The results from the analysis, carried out within the secure server, are demonstrated to be of use for remote monitoring. This knowledge will be useful in establishing biomarkers related to a possible deterioration in a patient's health or for assessing the impact of clinical interventions
How consent is constructed in case reports of rape : an analysis of judicial discourse
Get PDFIn a jurisdiction where the definition of rape is based on consent, how consent is understood and assessed is of paramount importance. While the concept of consent is fundamental to the definition and proof of rape, there is considerable disagreement about the nature of consent, how it is conceptualised and determined in different circumstances. My study examines the construction of consent in case reports of rape by applying a methodology based on discourse analysis. By examining case reports between 2002 and 2015, I demonstrate the diversity and evolution of judicial discourse and the impact of the Sexual Offences (S) Act 2009 on judicial assessment of consent. The study focuses on judicial discourse rather than judicial doctrine. This allows me to consider how consent is established through judicial handling of the facts as well as the application of law. By reading across the cases, I identify and examine four key aspects of judicial discourse that demonstrate how consent is constructed: the relevance of force in determining consent; how particular patterns of behaviour are understood in judicial discourse; the value attached to the complainer's response to rape and her expression of distress; how consent is understood in circumstances where the complainer is asleep or in a borderline state of consciousness. My study reveals a complex picture of an evolving discourse and heterogeneous ideas about consent. While there is greater fluidity and richness in judicial thinking about consent following the 2009 Act, entrenched ideas about gender, intoxication and sexual availability persist. I also identify new problems emerging in the wake of the 2009 Act. By advancing our understanding of judicial decision-making about consent and the development of judicial discourse in the context of the 2009 Act, the study makes an original contribution to legal scholarship in the area of sexual consent and rape.In a jurisdiction where the definition of rape is based on consent, how consent is understood and assessed is of paramount importance. While the concept of consent is fundamental to the definition and proof of rape, there is considerable disagreement about the nature of consent, how it is conceptualised and determined in different circumstances. My study examines the construction of consent in case reports of rape by applying a methodology based on discourse analysis. By examining case reports between 2002 and 2015, I demonstrate the diversity and evolution of judicial discourse and the impact of the Sexual Offences (S) Act 2009 on judicial assessment of consent. The study focuses on judicial discourse rather than judicial doctrine. This allows me to consider how consent is established through judicial handling of the facts as well as the application of law. By reading across the cases, I identify and examine four key aspects of judicial discourse that demonstrate how consent is constructed: the relevance of force in determining consent; how particular patterns of behaviour are understood in judicial discourse; the value attached to the complainer's response to rape and her expression of distress; how consent is understood in circumstances where the complainer is asleep or in a borderline state of consciousness. My study reveals a complex picture of an evolving discourse and heterogeneous ideas about consent. While there is greater fluidity and richness in judicial thinking about consent following the 2009 Act, entrenched ideas about gender, intoxication and sexual availability persist. I also identify new problems emerging in the wake of the 2009 Act. By advancing our understanding of judicial decision-making about consent and the development of judicial discourse in the context of the 2009 Act, the study makes an original contribution to legal scholarship in the area of sexual consent and rape
Studies on development of a Leishmanial vaccine
Get PDFLeishmaniasis is a disease caused by infection with the obligate intracellular parasite of the genus Leishmania. Leishmaniasis is a public health problem; it is estimated that approximately 12-15 million people worldwide are infected. An estimated 1.5-2 million new cases occur each year, 350 million people are at risk of infection, and it causes 70000 deaths per year.;Therefore, development of a vaccine to prevent infection is required. The overall aim of this study was to develop a vaccine to protect against Leishmania infection using live nonpathogenic L. tarentolae transfected with gamma glutamylcysteine synthetase (γGCS) from three different species (L. donovani, L. mexicana and L. major).;Previous studies for expressing recombinant γGCS using E. coli as an expression system have shown that it was not possible to produce pure full-length recombinant γGCS protein. Therefore, in this project, using an expression vector that is phylogenically more like Leishmania. L. tarentolae has been used as an expression system for eukayotic recombinant proteins.;Studies of the expression of L. donovani, L. mexicana and L. major γGCS recombinant proteins showed that parasites integrated with a green fluorescent protein γGCS-His gene gave stable expression of the fusion protein for six months without the requirement for antibiotics to maintain expression of the gene insert. Supplementing the culture medium with hydrogen peroxide (H2O2) increased proliferation of parasites in cell culture.;The addition of a 12 μM of H2O2 supplement increased the number of the parasites in cell culture, which can conclude that expression of the GFP-γGCS-His recombinant protein has been increased.;Expression of the recombinant GFP-γGCS-His protein produced full-length protein and truncated protein, but after isolation from an affinity column, it was impossible to produce pure full-length protein for all three transfected parasites. Therefore, this purification method failed to remove non-specific protein contamination.;The live non-pathogenic lizard parasite, L. tarentolae, expressing elected Leishmania antigens has recently provided a promising new approach as a safe and effective live vaccine candidate to prevent Leishmaniasis. Here, this study evaluated the immunoprotective potential of a live vaccine against L. major infection in BALB/c mice, using L. tarentolae transfected with the GFP-γGCS-His sequence gene from one of three different species (L. donovani, L. major or L. mexicana) or a 'triple vaccine' using a 1:1:1 mixture of L. tarentolae transfected with the GFP-γGCS-His sequence gene of the three pathogenic species;Vaccination with transfected L. tarentolae with GFP-γGCS-His gene from L. donovani, L. major and L. mexicana (triple vaccine) induced significant parasite specific Th1 immune responses based on antibody titres and cytokine production in vitro in stimulated splenocytes and popliteal lymph nodes from immunised mice.;Vaccination by subcutaneous injection with the triple vaccine caused the highest percentage reduction in parasite burdens compared to controls ± SE, was 94% ± 0.01 in L. major infected mice. Vaccination with L.t L. maj GFP-γGCS-His, L. mex GFP-γGCS-His and L. don GFP-γGCS-His parasites failed to give significant protection against L. major infection, but vaccination with L. t L. maj GFP-γGCSHis resulted in an 86% ± 0.01 suppression in parasite burden compared to controls.;In conclusion, the results of this study indicate that vaccination with transfected L. tarentolae parasites against L. major infection enhanced the protective efficacy and that the triple vaccine is a potential vaccine candidate.Leishmaniasis is a disease caused by infection with the obligate intracellular parasite of the genus Leishmania. Leishmaniasis is a public health problem; it is estimated that approximately 12-15 million people worldwide are infected. An estimated 1.5-2 million new cases occur each year, 350 million people are at risk of infection, and it causes 70000 deaths per year.;Therefore, development of a vaccine to prevent infection is required. The overall aim of this study was to develop a vaccine to protect against Leishmania infection using live nonpathogenic L. tarentolae transfected with gamma glutamylcysteine synthetase (γGCS) from three different species (L. donovani, L. mexicana and L. major).;Previous studies for expressing recombinant γGCS using E. coli as an expression system have shown that it was not possible to produce pure full-length recombinant γGCS protein. Therefore, in this project, using an expression vector that is phylogenically more like Leishmania. L. tarentolae has been used as an expression system for eukayotic recombinant proteins.;Studies of the expression of L. donovani, L. mexicana and L. major γGCS recombinant proteins showed that parasites integrated with a green fluorescent protein γGCS-His gene gave stable expression of the fusion protein for six months without the requirement for antibiotics to maintain expression of the gene insert. Supplementing the culture medium with hydrogen peroxide (H2O2) increased proliferation of parasites in cell culture.;The addition of a 12 μM of H2O2 supplement increased the number of the parasites in cell culture, which can conclude that expression of the GFP-γGCS-His recombinant protein has been increased.;Expression of the recombinant GFP-γGCS-His protein produced full-length protein and truncated protein, but after isolation from an affinity column, it was impossible to produce pure full-length protein for all three transfected parasites. Therefore, this purification method failed to remove non-specific protein contamination.;The live non-pathogenic lizard parasite, L. tarentolae, expressing elected Leishmania antigens has recently provided a promising new approach as a safe and effective live vaccine candidate to prevent Leishmaniasis. Here, this study evaluated the immunoprotective potential of a live vaccine against L. major infection in BALB/c mice, using L. tarentolae transfected with the GFP-γGCS-His sequence gene from one of three different species (L. donovani, L. major or L. mexicana) or a 'triple vaccine' using a 1:1:1 mixture of L. tarentolae transfected with the GFP-γGCS-His sequence gene of the three pathogenic species;Vaccination with transfected L. tarentolae with GFP-γGCS-His gene from L. donovani, L. major and L. mexicana (triple vaccine) induced significant parasite specific Th1 immune responses based on antibody titres and cytokine production in vitro in stimulated splenocytes and popliteal lymph nodes from immunised mice.;Vaccination by subcutaneous injection with the triple vaccine caused the highest percentage reduction in parasite burdens compared to controls ± SE, was 94% ± 0.01 in L. major infected mice. Vaccination with L.t L. maj GFP-γGCS-His, L. mex GFP-γGCS-His and L. don GFP-γGCS-His parasites failed to give significant protection against L. major infection, but vaccination with L. t L. maj GFP-γGCSHis resulted in an 86% ± 0.01 suppression in parasite burden compared to controls.;In conclusion, the results of this study indicate that vaccination with transfected L. tarentolae parasites against L. major infection enhanced the protective efficacy and that the triple vaccine is a potential vaccine candidate
Protein encapsulated gold nanoclusters for biological applications
Get PDFSensing and imaging at the nanoscale using fluorescence based techniques has advanced the fields of biology and medical science. However there remain shortfalls with currently used fluorescent probes. One such problem is the lack of biologically inert fluorophores which emit in the red regime of the visible spectrum with good brightness.;A class of newly developed fluorophores which have shown promise in fitting the required criteria are protein encapsulated gold nanoclusters (AuNCs). They have been shown to be non-toxic, red emitting, long-lived fluorophores however their low brightness has hindered their widespread use. The complexity of protein encapsulated AuNCs' fluorescence mechanism also remains poorly understood.;Fluorescence based techniques, Molecular Dynamics simulations and physicochemical characterisation techniques have been employed to uncover important information critical to improving the fluorescence characteristics of protein encapsulated AuNCs. The AuNCs nucleation site within Human Serum Albumin (HSA) has been discovered which will allow for the intelligent modification of the fluorophores with the aim of improving their fluorescence intensity and low quantum yield.;The effects of AuNCs on natural protein function have also been studied; indicating that the major drug binding site of HSA is blocked upon AuNCs synthesis. Further studies of the physicochemical changes in HSA upon AuNCs synthesis uncovered that the protein adopts a dimer state which could lead to complications when using as an in vivo sensor. Lysozyme encapsulated AuNCs displayed similar behaviour, forming dimers after AuNCs synthesis.;Interestingly, the isoelectric point of this fluorophore was found to be the same as HSA encapsulated AuNCs, suggesting that protein encapsulated AuNCs share common features. Lysozyme encapsulated AuNCs displayed similar adsorption properties as native lysozyme; suggesting that in the future, unmodified AuNCs could be used to observe the formation of lysozyme fibrils which are a major bio-marker for currently incurable brain diseases such as Alzheimer's and Parkinson's.Sensing and imaging at the nanoscale using fluorescence based techniques has advanced the fields of biology and medical science. However there remain shortfalls with currently used fluorescent probes. One such problem is the lack of biologically inert fluorophores which emit in the red regime of the visible spectrum with good brightness.;A class of newly developed fluorophores which have shown promise in fitting the required criteria are protein encapsulated gold nanoclusters (AuNCs). They have been shown to be non-toxic, red emitting, long-lived fluorophores however their low brightness has hindered their widespread use. The complexity of protein encapsulated AuNCs' fluorescence mechanism also remains poorly understood.;Fluorescence based techniques, Molecular Dynamics simulations and physicochemical characterisation techniques have been employed to uncover important information critical to improving the fluorescence characteristics of protein encapsulated AuNCs. The AuNCs nucleation site within Human Serum Albumin (HSA) has been discovered which will allow for the intelligent modification of the fluorophores with the aim of improving their fluorescence intensity and low quantum yield.;The effects of AuNCs on natural protein function have also been studied; indicating that the major drug binding site of HSA is blocked upon AuNCs synthesis. Further studies of the physicochemical changes in HSA upon AuNCs synthesis uncovered that the protein adopts a dimer state which could lead to complications when using as an in vivo sensor. Lysozyme encapsulated AuNCs displayed similar behaviour, forming dimers after AuNCs synthesis.;Interestingly, the isoelectric point of this fluorophore was found to be the same as HSA encapsulated AuNCs, suggesting that protein encapsulated AuNCs share common features. Lysozyme encapsulated AuNCs displayed similar adsorption properties as native lysozyme; suggesting that in the future, unmodified AuNCs could be used to observe the formation of lysozyme fibrils which are a major bio-marker for currently incurable brain diseases such as Alzheimer's and Parkinson's
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