7103 research outputs found
Sort by
Diaspora nationalism, the Dundee-Irish, and the experiences of Irish republican women in Britain, c.1916-1966
No full textThe leading women: The media representation of minor party leadership during the 2019 UK General Election
Full text linkThis thesis analyses the media representation of Nicola Sturgeon, Jo Swinson, and Arlene Foster during the 2019 UK General Election. Each politician within this thesis was serving in a different political system enabling an expansive look at the representation of political leadership across the UK. I examined newspapers, Twitter, and the televised election debates to review the self-presentation and representation of these three female politicians in mediated spaces. Amongst my selection of media, I reviewed the personal Twitter accounts of these political women, their media representation in London-based, Scottish, and Northern Irish national publications, and the televised debates broadcasted on the BBC, ITV, STV, and Channel 4. I analysed these three forms of media by using a mixed methods approach combining content analysis and critical discourse analysis.In this study, there were interesting differences between the three women in terms of explicitly gendered coverage: Foster's coverage was the least gendered, Swinson's the most. At the same time, the media representation of Sturgeon included gendered commentary that was positive in tone and used to present her as politically accomplished. The second prominent finding of the study was the variation in coverage between London-based, Scottish, and Northern Irish newspapers for each politician’s media representation. In addition, each party leader held political positions in different countries of the UK, revealing expressions of banal nationalism within their self-presentation. Notably, the reference to national belonging was most impactful in my Foster and Northern Irish datasets. Foster's selfpresentation and media representation were often focused on Northern Irish issues rather than the whole of the UK. Foster's prominence as a local figure in Northern Ireland and her constituency showed that various methods of analysis are needed to study politicians less prominent in a UK-wide election compared to political figures like Sturgeon and Swinson, who became a part of the national media agenda.This thesis analyses the media representation of Nicola Sturgeon, Jo Swinson, and Arlene Foster during the 2019 UK General Election. Each politician within this thesis was serving in a different political system enabling an expansive look at the representation of political leadership across the UK. I examined newspapers, Twitter, and the televised election debates to review the self-presentation and representation of these three female politicians in mediated spaces. Amongst my selection of media, I reviewed the personal Twitter accounts of these political women, their media representation in London-based, Scottish, and Northern Irish national publications, and the televised debates broadcasted on the BBC, ITV, STV, and Channel 4. I analysed these three forms of media by using a mixed methods approach combining content analysis and critical discourse analysis.In this study, there were interesting differences between the three women in terms of explicitly gendered coverage: Foster's coverage was the least gendered, Swinson's the most. At the same time, the media representation of Sturgeon included gendered commentary that was positive in tone and used to present her as politically accomplished. The second prominent finding of the study was the variation in coverage between London-based, Scottish, and Northern Irish newspapers for each politician’s media representation. In addition, each party leader held political positions in different countries of the UK, revealing expressions of banal nationalism within their self-presentation. Notably, the reference to national belonging was most impactful in my Foster and Northern Irish datasets. Foster's selfpresentation and media representation were often focused on Northern Irish issues rather than the whole of the UK. Foster's prominence as a local figure in Northern Ireland and her constituency showed that various methods of analysis are needed to study politicians less prominent in a UK-wide election compared to political figures like Sturgeon and Swinson, who became a part of the national media agenda
Development of new synthetic approaches in solid-phase peptide synthesis
No full textChapter 1 of this thesis will focus on the development of a synthetic route to access dual-labelled peptides using bioorthogonal reacting pairs. Since its inception in 2003, bioorthogonal chemistry is a growing area of chemistry which has greatly aided in the studies of biomolecules. We have developed a route which could facilitate the selective and sequential labelling of biomolecules through means of leveraging chemistry highlighted in literature. We have employed two orthogonal reacting pairs, nitrile imines with carboxylic acids and azides with aromatic ynamines, Figure 1. [Figure reproduced in thesis text] Nitrile imines are highly reactive 1,3-dipoles which can be accessed in situ through the photolytic degradation of 2,5-diaryl tetrazoles. Given their inherent dipole, they can undergo 1,3-dipolar cycloadditions as expected, however, through competition experimental studies we have shown that NIs will preferentially react with carboxylicacids when exposed to a dipolarophile, such as an aromatic ynamine. Aromatic ynamines have been shown to provide high selectivity in CuAAC over aliphatic alkynes. We have shown that both of these processes can occur orthogonally to one another and can be applied to a biomolecule setting, Scheme 1. [Figure reproduced in thesis text] Chapter 2 of this report will shift the focus onto the solvents used to synthesise peptides. Typically, the solvent of choice employed in SPPS is N,N’-dimethylformamide (DMF) which is highly toxic as it is teratogenic and with that, restrictions around its sale and manufacture are being tightened as of December 2023. Therefore, the requirement to identify a robust replacement for this crucial process is of the utmost importance. We report the development of an interactive solvent selection guide for SPPS andconduct studies examining solvents ability to swell resins in addition to solubilising amino acids and coupling reagents which identified cyclopentanone as a potential candidate to replace DMF, and when applied to SPPS, we were successful in synthesising a pentapeptide with good crude purity.Chapter 1 of this thesis will focus on the development of a synthetic route to access dual-labelled peptides using bioorthogonal reacting pairs. Since its inception in 2003, bioorthogonal chemistry is a growing area of chemistry which has greatly aided in the studies of biomolecules. We have developed a route which could facilitate the selective and sequential labelling of biomolecules through means of leveraging chemistry highlighted in literature. We have employed two orthogonal reacting pairs, nitrile imines with carboxylic acids and azides with aromatic ynamines, Figure 1. [Figure reproduced in thesis text] Nitrile imines are highly reactive 1,3-dipoles which can be accessed in situ through the photolytic degradation of 2,5-diaryl tetrazoles. Given their inherent dipole, they can undergo 1,3-dipolar cycloadditions as expected, however, through competition experimental studies we have shown that NIs will preferentially react with carboxylicacids when exposed to a dipolarophile, such as an aromatic ynamine. Aromatic ynamines have been shown to provide high selectivity in CuAAC over aliphatic alkynes. We have shown that both of these processes can occur orthogonally to one another and can be applied to a biomolecule setting, Scheme 1. [Figure reproduced in thesis text] Chapter 2 of this report will shift the focus onto the solvents used to synthesise peptides. Typically, the solvent of choice employed in SPPS is N,N’-dimethylformamide (DMF) which is highly toxic as it is teratogenic and with that, restrictions around its sale and manufacture are being tightened as of December 2023. Therefore, the requirement to identify a robust replacement for this crucial process is of the utmost importance. We report the development of an interactive solvent selection guide for SPPS andconduct studies examining solvents ability to swell resins in addition to solubilising amino acids and coupling reagents which identified cyclopentanone as a potential candidate to replace DMF, and when applied to SPPS, we were successful in synthesising a pentapeptide with good crude purity
Internal load modelling of tapered-roller main bearings in wind turbines
Full text linkThe replacement of double-row spherical roller bearings with double-row tapered roller bearings as the main shaft support in wind turbines has been proposed as one of the solutions to the premature failures affecting the industry. In order to improve our scientific knowledge of tapered roller bearing loading in wind turbine main shafts, this thesis sets out to explore how these components may be modelled, how such models can be utilised to improve the understanding of their operational characteristics in relation to the inflow wind, and to compare their behaviour with that of spherical roller bearings. Novel drivetrain models with tapered roller main bearings are developed in this thesis with capabilities of evaluating internal component loading while accounting for variations in system sti↵ness at different operating points.The findings demonstrate that modelling the moment reaction behaviour of tapered-roller bearings is crucial for even simplistic representations, since moment loads at the wind turbine hub are key drivers of bearing displacement. The models developed here are used in an extensive analysis to determine characteristics and sensitivities regarding operational conditions experienced by double-row tapered roller bearings under realistic turbulent inflow conditions, while properly accounting for the system load-response behaviour, roller load distributions and impacts on bearing fatigue life ratings. The presence of “looped” loading structures and evidence of consistent roller edge-loading throughout normal operation is demonstrated, and load response was also found to be largely shared between the two roller rows, this contrasts strongly with the conditions known to hold for spherical-roller main bearings.High levels of fatigue life sensitivity to both operational and lubrication conditions are documented, and shear effects in the wind were found to have opposite effects depending on the bearing type in use, with increased shear exponents drastically reducing the fatigue life rating of the tapered roller bearing. Crucially, this work demonstrates the uniqueness of load conditions experienced by tapered roller bearings in wind turbines, indicating that experience developed in more conventional rolling bearing applications should not be reapplied blindly without first determining its validity in this application space.The replacement of double-row spherical roller bearings with double-row tapered roller bearings as the main shaft support in wind turbines has been proposed as one of the solutions to the premature failures affecting the industry. In order to improve our scientific knowledge of tapered roller bearing loading in wind turbine main shafts, this thesis sets out to explore how these components may be modelled, how such models can be utilised to improve the understanding of their operational characteristics in relation to the inflow wind, and to compare their behaviour with that of spherical roller bearings. Novel drivetrain models with tapered roller main bearings are developed in this thesis with capabilities of evaluating internal component loading while accounting for variations in system sti↵ness at different operating points.The findings demonstrate that modelling the moment reaction behaviour of tapered-roller bearings is crucial for even simplistic representations, since moment loads at the wind turbine hub are key drivers of bearing displacement. The models developed here are used in an extensive analysis to determine characteristics and sensitivities regarding operational conditions experienced by double-row tapered roller bearings under realistic turbulent inflow conditions, while properly accounting for the system load-response behaviour, roller load distributions and impacts on bearing fatigue life ratings. The presence of “looped” loading structures and evidence of consistent roller edge-loading throughout normal operation is demonstrated, and load response was also found to be largely shared between the two roller rows, this contrasts strongly with the conditions known to hold for spherical-roller main bearings.High levels of fatigue life sensitivity to both operational and lubrication conditions are documented, and shear effects in the wind were found to have opposite effects depending on the bearing type in use, with increased shear exponents drastically reducing the fatigue life rating of the tapered roller bearing. Crucially, this work demonstrates the uniqueness of load conditions experienced by tapered roller bearings in wind turbines, indicating that experience developed in more conventional rolling bearing applications should not be reapplied blindly without first determining its validity in this application space
Exploring the determinants of organisational e-commerce adoption : an analysis of e-readiness and technological and behavioural control factors using PLS-SEM and multinomial regression
Full text linkE-Commerce technologies are widely adopted by organisations for increased efficiency and competitive edge in both public and private sectors. Statistical evidence shows that E-Commerce adoption in developing economies is low and firms in these regions face adoption challenges distinct from those in developed countries. However, despite some shared challenges generalisation of results from one developing country to the other requires great caution. The term “Developing Countries” is not distinctive and a significant variance in socio-economic factors exists in this block. Given the sensitivity of E-Commerce adoption to such factors, country-specific research is required for better understanding. E-commerce is a driver of economic growth and e-commerce adoption by developing countries is not only essential for their prosperity but is also pivotal for sustainable global economic development in an interconnected world. Pakistan holds significant potential to boost the global economy, yet its E-Commerce adoption trails behind several regional players. The literature survey reveals a scarcity of high-quality Pakistan-based studies, with many failing to adhere to statistical and general research principles. Most of these studies focus on “usual suspects” and terminate at the initial adoption of organisational E-Commerce. This quantitative study utilised correlational and classification techniques to investigate the influence of more pertinent factors on firm-level ECommerce adoption within the unique context of Pakistan. By empirically testing four models developed using constructs from the Perceived E-Commerce Readiness Model (PERM), Theory of Reasoned Action (TRA), and
Technology, Organisation, Environment (TOE), the study addressed four research questions. A distinct feature of this study is the comparison of E-Commerce adoption decisions in public and private sectors, providing insights into potential disparities and unique challenges faced by each sector. A range of univariate and multivariate techniques were used in the study including Partial Least Square Structural Equation Modelling (PLS-SEM) and Multinominal Logistic Regression. Using the stratified sampling technique questionnaires were sent to potential respondents in two phases. The impact of E-readiness factors was examined using 448 valid responses received in phase 1. In the second phase, 347 valid responses were received, which were then used to examine the effects of technological and behavioural factors on an organisation's E-Commerce adoption decision. The study found that the E-Readiness of “Business Resources”, “Technical Resources”, “Government”, “Governance”, and “Support Industry”, along with “Awareness” about E-Commerce and “Commitment” impact E-Commerce adoption. Among Technological and Behavioural Control Factors, Perceived Behavioural Control, “Perceived Compatibility”, “Relative Advantage” and “Perceived Security” were found positively related to E-Commerce adoption in Pakistan. The study also identified the relevance of factors at different stages of organisational E-Commerce adoption. While some factors remained
relevant in all stages, their impact varied in magnitude at different levels of E-Commerce adoption in organisations. The study also highlighted some interesting differences between the public and private sectors. Private sector
organisations scored higher in terms of perceived E-Readiness, Technological and Behavioural Control Factors. ECommerce adoption cost was found relevant only in the private sector as in the public sector its effect was
statistically insignificant. In terms of magnitude, relative advantage and cost acceptability were found more strongly and statistically significantly related to organisational E-Commerce adoption in the private sector compared to the
public sector. This study contributed to existing knowledge by explaining the variance in organisational E-commerce adoption decisions, incorporating E-readiness alongside various technological and behavioural factors. A systematic survey was essential to address the research questions effectively, resulting in a comprehensive literature review specifically focused on the context of Pakistan. The findings of this study offer valuable insights for decision-makers at both the national and organisational levels for the promotion of E-Commerce in Pakistan. This study highlighted the importance of E-Readiness, Technological, and Behavioural control factors, paving the way for future research to develop concise scales for auditing these factors and potentially integrating them into a unified model.E-Commerce technologies are widely adopted by organisations for increased efficiency and competitive edge in both public and private sectors. Statistical evidence shows that E-Commerce adoption in developing economies is low and firms in these regions face adoption challenges distinct from those in developed countries. However, despite some shared challenges generalisation of results from one developing country to the other requires great caution. The term “Developing Countries” is not distinctive and a significant variance in socio-economic factors exists in this block. Given the sensitivity of E-Commerce adoption to such factors, country-specific research is required for better understanding. E-commerce is a driver of economic growth and e-commerce adoption by developing countries is not only essential for their prosperity but is also pivotal for sustainable global economic development in an interconnected world. Pakistan holds significant potential to boost the global economy, yet its E-Commerce adoption trails behind several regional players. The literature survey reveals a scarcity of high-quality Pakistan-based studies, with many failing to adhere to statistical and general research principles. Most of these studies focus on “usual suspects” and terminate at the initial adoption of organisational E-Commerce. This quantitative study utilised correlational and classification techniques to investigate the influence of more pertinent factors on firm-level ECommerce adoption within the unique context of Pakistan. By empirically testing four models developed using constructs from the Perceived E-Commerce Readiness Model (PERM), Theory of Reasoned Action (TRA), and
Technology, Organisation, Environment (TOE), the study addressed four research questions. A distinct feature of this study is the comparison of E-Commerce adoption decisions in public and private sectors, providing insights into potential disparities and unique challenges faced by each sector. A range of univariate and multivariate techniques were used in the study including Partial Least Square Structural Equation Modelling (PLS-SEM) and Multinominal Logistic Regression. Using the stratified sampling technique questionnaires were sent to potential respondents in two phases. The impact of E-readiness factors was examined using 448 valid responses received in phase 1. In the second phase, 347 valid responses were received, which were then used to examine the effects of technological and behavioural factors on an organisation's E-Commerce adoption decision. The study found that the E-Readiness of “Business Resources”, “Technical Resources”, “Government”, “Governance”, and “Support Industry”, along with “Awareness” about E-Commerce and “Commitment” impact E-Commerce adoption. Among Technological and Behavioural Control Factors, Perceived Behavioural Control, “Perceived Compatibility”, “Relative Advantage” and “Perceived Security” were found positively related to E-Commerce adoption in Pakistan. The study also identified the relevance of factors at different stages of organisational E-Commerce adoption. While some factors remained
relevant in all stages, their impact varied in magnitude at different levels of E-Commerce adoption in organisations. The study also highlighted some interesting differences between the public and private sectors. Private sector
organisations scored higher in terms of perceived E-Readiness, Technological and Behavioural Control Factors. ECommerce adoption cost was found relevant only in the private sector as in the public sector its effect was
statistically insignificant. In terms of magnitude, relative advantage and cost acceptability were found more strongly and statistically significantly related to organisational E-Commerce adoption in the private sector compared to the
public sector. This study contributed to existing knowledge by explaining the variance in organisational E-commerce adoption decisions, incorporating E-readiness alongside various technological and behavioural factors. A systematic survey was essential to address the research questions effectively, resulting in a comprehensive literature review specifically focused on the context of Pakistan. The findings of this study offer valuable insights for decision-makers at both the national and organisational levels for the promotion of E-Commerce in Pakistan. This study highlighted the importance of E-Readiness, Technological, and Behavioural control factors, paving the way for future research to develop concise scales for auditing these factors and potentially integrating them into a unified model
Reliability-constrained design optimisation of extra-large offshore wind turbine support structures
Full text linkThe offshore wind industry has evolved significantly over the last decade, contributing
considerably to Europe’s energy mix. For further penetration of this technology, it is essential to reduce its costs to make it competitive with conventional power generation technologies. To this end, optimising the design of components while simultaneously fulfilling design criteria is a crucial requirement for producing more cost-effective strategies. Traditional design optimisation techniques rely on the optimisation of design variables against constraints such as stresses or deformation in the form of limit states and to minimise an objective function such as the total mass of a component. Although this approach leads to more optimal designs, the presence of uncertainties, for instance, in material properties, manufacturing tolerances and environmental loads, requires more systematic consideration of these uncertainties. A combination of optimisation methods with concepts of structural reliability can be a suitable approach if challenges such as the approximation of the load effect concerning global input
loads and computational requirements are addressed accordingly. In this study, a reliability-constrained optimisation framework for offshore wind turbine (OWT) support structures is developed, applied, and documented for the first time. First, a parametric finite element analysis (FEA) model of OWT support structures is developed,
considering stochastic material properties and environmental loads. The parametric FEA model is then combined with response surface and Monte Carlo (MC) to create an assessment model in the Six Sigma module in ANSYS, which is then further integrated with an optimisation algorithm to develop a fully coupled reliability-constrained optimisation framework. The framework is applied to the NREL 5MW OWT and OC3 sub-structure. Results indicate that the proposed optimisation framework can effectively reduce the mass of OWT support structures meeting target reliability levels focusing on realistic limit states. At the end of the optimisation loop, an LCOE comparison is done to see the effect of mass reduction on the wind turbine cost. The study expanded with a scaling-up approach and investigated the technical feasibility of increasing the system’s power and size in deeper water depth for bottom-fixed support structures. Additionally, parametric equations have been developed to estimate the wind turbine rating and weight considering water depth in the conceptual design stage. Furthermore, the sensitivity analysis was performed on the latest reference support structure of the IEA 15MW turbine to see the effect of water depth between 30m to 60m. The results showed the influences of water depth on the current structural response of the monopile. It revealed that utilising the proposed support structure is not feasible for water-depth above 50m as the analysis did not fulfil design criteria.The offshore wind industry has evolved significantly over the last decade, contributing
considerably to Europe’s energy mix. For further penetration of this technology, it is essential to reduce its costs to make it competitive with conventional power generation technologies. To this end, optimising the design of components while simultaneously fulfilling design criteria is a crucial requirement for producing more cost-effective strategies. Traditional design optimisation techniques rely on the optimisation of design variables against constraints such as stresses or deformation in the form of limit states and to minimise an objective function such as the total mass of a component. Although this approach leads to more optimal designs, the presence of uncertainties, for instance, in material properties, manufacturing tolerances and environmental loads, requires more systematic consideration of these uncertainties. A combination of optimisation methods with concepts of structural reliability can be a suitable approach if challenges such as the approximation of the load effect concerning global input
loads and computational requirements are addressed accordingly. In this study, a reliability-constrained optimisation framework for offshore wind turbine (OWT) support structures is developed, applied, and documented for the first time. First, a parametric finite element analysis (FEA) model of OWT support structures is developed,
considering stochastic material properties and environmental loads. The parametric FEA model is then combined with response surface and Monte Carlo (MC) to create an assessment model in the Six Sigma module in ANSYS, which is then further integrated with an optimisation algorithm to develop a fully coupled reliability-constrained optimisation framework. The framework is applied to the NREL 5MW OWT and OC3 sub-structure. Results indicate that the proposed optimisation framework can effectively reduce the mass of OWT support structures meeting target reliability levels focusing on realistic limit states. At the end of the optimisation loop, an LCOE comparison is done to see the effect of mass reduction on the wind turbine cost. The study expanded with a scaling-up approach and investigated the technical feasibility of increasing the system’s power and size in deeper water depth for bottom-fixed support structures. Additionally, parametric equations have been developed to estimate the wind turbine rating and weight considering water depth in the conceptual design stage. Furthermore, the sensitivity analysis was performed on the latest reference support structure of the IEA 15MW turbine to see the effect of water depth between 30m to 60m. The results showed the influences of water depth on the current structural response of the monopile. It revealed that utilising the proposed support structure is not feasible for water-depth above 50m as the analysis did not fulfil design criteria
How can UK corporate governance law enhance LGBT dignity protection?
Full text linkLGBT people are equally entitled to human dignity as others are entitled to in human community/society. To respect LGBT people’s dignity, the law plays a role in substantiating and protecting LGBT people’s interests in all aspects of life: LGBT people’s ‘full membership’. LGBT dignity protection has been developed, inter alia, in human rights law, the law of employment and service provision, family law, immigration law and equality law in the UK jurisdiction. This thesis aims at introducing corporate governance to contribute to LGBT dignity protection in the UK. It will answer the question how UK Corporate Governance law can be changed to enhance LGBT dignity protection. The focused problem in this thesis is that LGBT people can experience expressive harm in corporate activities, including service provision and employment areas. UK Equality law provides ‘extra protection’ on freely expressing/manifesting beliefs or opinions, which involve objection to LGBT identities and interests, such as objection to same-sex life in Christianity beliefs. Individuals can be allowed by the law to go beyond ‘mere disapproval’ and (intentionally or unintentionally) to deliver heterosexual and cisgender superiority implications through service provision and employment areas. The expressions/manifestations can ‘pull’ LGBT people from the ‘equal high rank’ among human community, but those speakers are not legally required with any responsibility for this LGBT expressive harm. I contend that corporate directors and managers are not mandated with duties to address this expressive harm to LGBT people in the UK jurisdiction. In Equality law, the UK proportionate approach is focused on merely dealing with material harm (e.g. discrimination) and does not provide much legal guidance on tackling expressive harm. More importantly, UK Corporate Governance law does not impose legal obligations for directors to tackle expressive harm to LGBT people in corporate activities. S.172 (1) of the Companies Act 2006, as a key source of UK Corporate Governance law, mandates directors to promote the success of the company for the ultimate purpose of shareholders’ interests. The statutory principle imposes little obligation on directors to seriously protect stakeholders’ interests, including but not limited to employees, customers and people in the local society in the UK. From the perspective of directors’ duties, UK Corporate Governance law allows directors to disappoint LGBT stakeholders/people, leaving them in the expressive harm sufferings through companies. In order to enhance LGBT dignity protection in corporate world, this thesis adopts the transformative corporate social responsibility (CSR) theoretical approach and promotes changes in UK Corporate Governance law. Corporate purpose is about more than mere profitmaking and shareholders’ wealth objectives. Protecting stakeholders’ interests should be a substantive objective. The transformative CSR approach intends to widen directors’ duties and presents that directors should sacrifice profit-making and shareholder wealth creation for the purpose of stakeholder protection. It will embody substantive stakeholder protection in corporate purpose. The transformative CSR approach marks a shift from profit-maximisation to profit-sacrificing social responsibilities in corporate governance. To bridge corporate responsibility and LGBT dignity protection, this thesis adopts the radical feminist ‘care and compassion’ principle to strengthen the role of transformative CSR in challenging corporate heterosexual (and cisgender) superiority culture. The radical feminist perspectives demonstrate that the ‘care and compassion’ to LGBT stakeholders/people means protecting LGBT stakeholders’ human rights and interests in corporate life. It also demonstrates that directors should exercise power to overturn LGBT subordination, encouraging to integrate LGBT dignity protection ‘lessons’ (UK Equality law) into UK Corporate Governance law. Following from the theoretical discussions, this thesis proposes an independent LGBT due diligence process in the UK Corporate Governance law in order to address the LGBT expressive harm. In this process, there would be a central mandatory duty – LGBT due diligence duty – for directors to identify, prevent and mitigate expressions and manifestations which involve objections to LGBT interests in corporate activities, for the purpose of respecting LGBT dignity. This duty echoes the transformative CSR approach, widening directors’ duties; also, this duty echoes the radical feminist ‘care and compassion’ principle, intending to overturn LGBT subordination. To strengthen the central duty, this thesis proposes to create two supportive CSR-related mechanisms, including the mandatory LGBT due diligence reporting and the LGBT stakeholder engagement (soft-law), to enhance scrutinisation. The main findings are that the proposed LGBT due diligence process can weaken shareholder primacy but also strengthen UK Corporate Governance law to enhance LGBT tolerance through companies. Furthermore, the proposed governance change in corporate entities can set an example for the law of other organisations or entities, such as partnerships, financial sectors, charities and public authorities, to learn how to enhance LGBT dignity protection in the relevant service and provision areas. Nevertheless, the LGBT due diligence process, as an initial proposal, may not completely overturn shareholder primacy in UK Corporate Governance law; it can encounter other challenges and limitations. To strengthen this proposal as a more LGBT-affirmative mechanism, this research implies more radical changes on corporate purpose and responsibility in the UK corporate legal framework and more changes in UK Equality law that can provide direct ‘legal guidance’ on corporate governance.LGBT people are equally entitled to human dignity as others are entitled to in human community/society. To respect LGBT people’s dignity, the law plays a role in substantiating and protecting LGBT people’s interests in all aspects of life: LGBT people’s ‘full membership’. LGBT dignity protection has been developed, inter alia, in human rights law, the law of employment and service provision, family law, immigration law and equality law in the UK jurisdiction. This thesis aims at introducing corporate governance to contribute to LGBT dignity protection in the UK. It will answer the question how UK Corporate Governance law can be changed to enhance LGBT dignity protection. The focused problem in this thesis is that LGBT people can experience expressive harm in corporate activities, including service provision and employment areas. UK Equality law provides ‘extra protection’ on freely expressing/manifesting beliefs or opinions, which involve objection to LGBT identities and interests, such as objection to same-sex life in Christianity beliefs. Individuals can be allowed by the law to go beyond ‘mere disapproval’ and (intentionally or unintentionally) to deliver heterosexual and cisgender superiority implications through service provision and employment areas. The expressions/manifestations can ‘pull’ LGBT people from the ‘equal high rank’ among human community, but those speakers are not legally required with any responsibility for this LGBT expressive harm. I contend that corporate directors and managers are not mandated with duties to address this expressive harm to LGBT people in the UK jurisdiction. In Equality law, the UK proportionate approach is focused on merely dealing with material harm (e.g. discrimination) and does not provide much legal guidance on tackling expressive harm. More importantly, UK Corporate Governance law does not impose legal obligations for directors to tackle expressive harm to LGBT people in corporate activities. S.172 (1) of the Companies Act 2006, as a key source of UK Corporate Governance law, mandates directors to promote the success of the company for the ultimate purpose of shareholders’ interests. The statutory principle imposes little obligation on directors to seriously protect stakeholders’ interests, including but not limited to employees, customers and people in the local society in the UK. From the perspective of directors’ duties, UK Corporate Governance law allows directors to disappoint LGBT stakeholders/people, leaving them in the expressive harm sufferings through companies. In order to enhance LGBT dignity protection in corporate world, this thesis adopts the transformative corporate social responsibility (CSR) theoretical approach and promotes changes in UK Corporate Governance law. Corporate purpose is about more than mere profitmaking and shareholders’ wealth objectives. Protecting stakeholders’ interests should be a substantive objective. The transformative CSR approach intends to widen directors’ duties and presents that directors should sacrifice profit-making and shareholder wealth creation for the purpose of stakeholder protection. It will embody substantive stakeholder protection in corporate purpose. The transformative CSR approach marks a shift from profit-maximisation to profit-sacrificing social responsibilities in corporate governance. To bridge corporate responsibility and LGBT dignity protection, this thesis adopts the radical feminist ‘care and compassion’ principle to strengthen the role of transformative CSR in challenging corporate heterosexual (and cisgender) superiority culture. The radical feminist perspectives demonstrate that the ‘care and compassion’ to LGBT stakeholders/people means protecting LGBT stakeholders’ human rights and interests in corporate life. It also demonstrates that directors should exercise power to overturn LGBT subordination, encouraging to integrate LGBT dignity protection ‘lessons’ (UK Equality law) into UK Corporate Governance law. Following from the theoretical discussions, this thesis proposes an independent LGBT due diligence process in the UK Corporate Governance law in order to address the LGBT expressive harm. In this process, there would be a central mandatory duty – LGBT due diligence duty – for directors to identify, prevent and mitigate expressions and manifestations which involve objections to LGBT interests in corporate activities, for the purpose of respecting LGBT dignity. This duty echoes the transformative CSR approach, widening directors’ duties; also, this duty echoes the radical feminist ‘care and compassion’ principle, intending to overturn LGBT subordination. To strengthen the central duty, this thesis proposes to create two supportive CSR-related mechanisms, including the mandatory LGBT due diligence reporting and the LGBT stakeholder engagement (soft-law), to enhance scrutinisation. The main findings are that the proposed LGBT due diligence process can weaken shareholder primacy but also strengthen UK Corporate Governance law to enhance LGBT tolerance through companies. Furthermore, the proposed governance change in corporate entities can set an example for the law of other organisations or entities, such as partnerships, financial sectors, charities and public authorities, to learn how to enhance LGBT dignity protection in the relevant service and provision areas. Nevertheless, the LGBT due diligence process, as an initial proposal, may not completely overturn shareholder primacy in UK Corporate Governance law; it can encounter other challenges and limitations. To strengthen this proposal as a more LGBT-affirmative mechanism, this research implies more radical changes on corporate purpose and responsibility in the UK corporate legal framework and more changes in UK Equality law that can provide direct ‘legal guidance’ on corporate governance
Investigating the importance of LmxOSM3.1 phosphorylation in flagella development and determining LmxOSM3.1 and LmxMPK13 interaction partners
No full textParasitic infection induced by the protozoan Leishmania from the Trypanosomatidae family causes
Leishmaniasis with the female sand fly being the primary vector of transmission. Leishmaniasis is
endemic across many tropical regions. However, climate change, urbanisation and deforestation are
propagating its global distribution to unaffected regions. Hence, the estimated global population of
12 million people with Leishmaniasis is anticipated to increase. Current anti-leishmaniasis drugs
including pentavalent antimonials, amphotericin B, miltefosine, paromomycin, and pentamidine are
limited in their drug potency, and demonstrate extensive drug resistance. Novel drug treatments are
needed to combat these limitations. Kinases and kinesins are suggested to be effective drug targets
that could target flagella growth in Leishmania. LmxOSM3.1 is proposed to be a plus end-directed
170kDa, homodimeric N-kinesin involved in mediating anterograde transport in the flagellum.
CeOSM3 p802 null mutants induce a loss in the sensory ciliary distal domain of Caenorhabditis
elegans with a 37-50% decrease in cilium length. LmxOSM3.1 is therefore proposed to be important
in the regulation of flagella length in L. mexicana. The kinase domain of LmxMPK13 displays
homology to the Homo sapiens MOK and Chlamydomonas reinhardtii LF4 with MOK/LF4
downregulation promoting ciliary elongation. As LmxOSM3.1 and LmxMPK13 are involved in flagella
regulation, it is hypothesised that LmxOSM3.1 is a substrate of LmxMPK13 and together they
mediate flagellum length. To determine if LmxOSM3.1 and LmxMPK13 interact with each other, the 2C-miniTurbo assay was
conducted. Using CRISPR-Cas9, the fusion protein FRB which binds to FKBP was tagged to the 5’ end
of LmxMPK13 and 3’ end of LmxOSM3.1 for proximity labelling. To achieve this donor DNA (FRBLmxMPK13 and LmxOSM3.1-FRB) was generated by PCR and purified. Then electroporated into the
LmxA1B5 cell line containing the CRISPR-Cas9 machinery with the miniTurbo biotin ligase fused to
FKBP. Following electroporation, 6 transfectants were selected and cultured. Lmx_A2 and Lmx_E5
carrying FRB-LmxMPK13 and LmxOSM3.1-FRB, respectively, were treated with rapamycin and biotin
to permit FRB-FKBP oligomerisation and biotinylation of potential proteins in close vicinity to
LmxMPK13 and LmxOSM3.1, and then analysed by mass spectrometry. For technical reasons mass
spectrometry analysis failed for clone Lmx_E5 and could not be repeated due to time constraints.
Mass spectrometry for clone Lmx_A2 resulted in a considerable list of putative interaction partners
but it failed to yield LmxOSM3.1 as an interaction partner of LmxMPK13. Further research is
necessary to examine the potential interaction between LmOSM3.1 and LmxMPK13. The phosphorylation of kinesins via kinases has shown to be important in governing the primary
motor activity of kinesins. Thus, the effects of phosphorylating LmxOSM3.1 towards flagella length
was explored in vivo by electroporating into Leishmania plasmids to replace LmxOSM3.1 with
LmxOSM3.1GFP encoding C-terminally GFP tagged wild-type, S477A, and S477D LmxOSM3.1
mutants. However, Leishmania cells transfected with LmxOSM3.1GFP, LmxOSM3.1SAGFP and
LmxOSM3.1SDGFP failed to show green fluorescent signals when analysed by microscopy. The Cterminal fusion of GFP to LmxOSM3.1 and the N-terminal 6xHis tag may have impacted LmxOSM3.1
activity causing no green fluorescent signals to be observed in the clones. Therefore, the hypothesis
could not be supported. Further research is required to support LmxOSM3.1 as a substrate of
LmxMPK13 and to examine the role of phosphorylating Ser477 in LmxOSM3.1 to mediate flagella
length.Parasitic infection induced by the protozoan Leishmania from the Trypanosomatidae family causes
Leishmaniasis with the female sand fly being the primary vector of transmission. Leishmaniasis is
endemic across many tropical regions. However, climate change, urbanisation and deforestation are
propagating its global distribution to unaffected regions. Hence, the estimated global population of
12 million people with Leishmaniasis is anticipated to increase. Current anti-leishmaniasis drugs
including pentavalent antimonials, amphotericin B, miltefosine, paromomycin, and pentamidine are
limited in their drug potency, and demonstrate extensive drug resistance. Novel drug treatments are
needed to combat these limitations. Kinases and kinesins are suggested to be effective drug targets
that could target flagella growth in Leishmania. LmxOSM3.1 is proposed to be a plus end-directed
170kDa, homodimeric N-kinesin involved in mediating anterograde transport in the flagellum.
CeOSM3 p802 null mutants induce a loss in the sensory ciliary distal domain of Caenorhabditis
elegans with a 37-50% decrease in cilium length. LmxOSM3.1 is therefore proposed to be important
in the regulation of flagella length in L. mexicana. The kinase domain of LmxMPK13 displays
homology to the Homo sapiens MOK and Chlamydomonas reinhardtii LF4 with MOK/LF4
downregulation promoting ciliary elongation. As LmxOSM3.1 and LmxMPK13 are involved in flagella
regulation, it is hypothesised that LmxOSM3.1 is a substrate of LmxMPK13 and together they
mediate flagellum length. To determine if LmxOSM3.1 and LmxMPK13 interact with each other, the 2C-miniTurbo assay was
conducted. Using CRISPR-Cas9, the fusion protein FRB which binds to FKBP was tagged to the 5’ end
of LmxMPK13 and 3’ end of LmxOSM3.1 for proximity labelling. To achieve this donor DNA (FRBLmxMPK13 and LmxOSM3.1-FRB) was generated by PCR and purified. Then electroporated into the
LmxA1B5 cell line containing the CRISPR-Cas9 machinery with the miniTurbo biotin ligase fused to
FKBP. Following electroporation, 6 transfectants were selected and cultured. Lmx_A2 and Lmx_E5
carrying FRB-LmxMPK13 and LmxOSM3.1-FRB, respectively, were treated with rapamycin and biotin
to permit FRB-FKBP oligomerisation and biotinylation of potential proteins in close vicinity to
LmxMPK13 and LmxOSM3.1, and then analysed by mass spectrometry. For technical reasons mass
spectrometry analysis failed for clone Lmx_E5 and could not be repeated due to time constraints.
Mass spectrometry for clone Lmx_A2 resulted in a considerable list of putative interaction partners
but it failed to yield LmxOSM3.1 as an interaction partner of LmxMPK13. Further research is
necessary to examine the potential interaction between LmOSM3.1 and LmxMPK13. The phosphorylation of kinesins via kinases has shown to be important in governing the primary
motor activity of kinesins. Thus, the effects of phosphorylating LmxOSM3.1 towards flagella length
was explored in vivo by electroporating into Leishmania plasmids to replace LmxOSM3.1 with
LmxOSM3.1GFP encoding C-terminally GFP tagged wild-type, S477A, and S477D LmxOSM3.1
mutants. However, Leishmania cells transfected with LmxOSM3.1GFP, LmxOSM3.1SAGFP and
LmxOSM3.1SDGFP failed to show green fluorescent signals when analysed by microscopy. The Cterminal fusion of GFP to LmxOSM3.1 and the N-terminal 6xHis tag may have impacted LmxOSM3.1
activity causing no green fluorescent signals to be observed in the clones. Therefore, the hypothesis
could not be supported. Further research is required to support LmxOSM3.1 as a substrate of
LmxMPK13 and to examine the role of phosphorylating Ser477 in LmxOSM3.1 to mediate flagella
length
Analysis of nucleation kinetics in pH-shift crystallization using agitated and microfluidic systems
No full textCrystal nucleation is a key event in the process of crystallization and is important in a number of processes in the pharmaceutical industry. Nucleation kinetics impact the crystal quality attributes of the product of a crystallization process. For example, increased crystal nucleationrate can lead to a smaller particle size distribution or increase the likelihood of presence of impurities or inclusions. A greater understanding of the fundamental principles underlying crystal nucleation allows for the development of better processes and tools for controlling this importantelement of crystallization. The aim of this work was to study nucleation kinetics in pH-shift crystallization of the amino acid DL-phenylalanine (a model compound) through data generated from isothermal induction time experiments in small scale agitated vials and in a novel microfluidic device. The objectives were to gain a detailed understanding of the model system, to accurately determine solubility and supersaturation, collect nucleation rate data in the model system using an established methodology based on the Crystal16 multiple reactor system, develop a novel microfluidic device forcollecting nucleation rate data and finally, to compare the nucleation rate data collected from the established and novel techniques. In order to work in this complex system, a model was developed using MATLAB for predictingthe pH and supersaturation from the solution composition and the dissociation constants for each component and applying the Davies extension of Debye-Huckel theory. This model was vital for designing experiments as it was not always possible to directly measure solution pH.Nucleation rates were estimated by fitting induction time data collected isothermally, under relevant conditions, to a cumulative probability distribution. A microfluidic device was developed as a tool for induction time determination in a pHshift crystallization system. The nucleation rates determined with this new technique were compared with data collected through a previously established methodology utilizing the Crystal 16 multiple reactor system. We report that nucleation in the microfluidic system behaves in a similar manner to other non-agitated systems with different regimes of nucleation kinetics: a nonnucleating regime, a slowly nucleating regime and a fast nucleating regime. As such, this type of data is best fitted to a double exponential curve. This behaviour is not yet fully understood, as agitated systems generally show a single nucleation regime, where induction time data can be fitted by a simple exponential curve. Therefore, it is not straightforward to directly compare nucleation rate obtained under agitated and non-agitated conditions. The microfluidic device presented can be used for non-agitated nucleation rate studies, however, further refinement ofthe design could improve control of crystallization conditions and extend its operational capacity and range.Crystal nucleation is a key event in the process of crystallization and is important in a number of processes in the pharmaceutical industry. Nucleation kinetics impact the crystal quality attributes of the product of a crystallization process. For example, increased crystal nucleationrate can lead to a smaller particle size distribution or increase the likelihood of presence of impurities or inclusions. A greater understanding of the fundamental principles underlying crystal nucleation allows for the development of better processes and tools for controlling this importantelement of crystallization. The aim of this work was to study nucleation kinetics in pH-shift crystallization of the amino acid DL-phenylalanine (a model compound) through data generated from isothermal induction time experiments in small scale agitated vials and in a novel microfluidic device. The objectives were to gain a detailed understanding of the model system, to accurately determine solubility and supersaturation, collect nucleation rate data in the model system using an established methodology based on the Crystal16 multiple reactor system, develop a novel microfluidic device forcollecting nucleation rate data and finally, to compare the nucleation rate data collected from the established and novel techniques. In order to work in this complex system, a model was developed using MATLAB for predictingthe pH and supersaturation from the solution composition and the dissociation constants for each component and applying the Davies extension of Debye-Huckel theory. This model was vital for designing experiments as it was not always possible to directly measure solution pH.Nucleation rates were estimated by fitting induction time data collected isothermally, under relevant conditions, to a cumulative probability distribution. A microfluidic device was developed as a tool for induction time determination in a pHshift crystallization system. The nucleation rates determined with this new technique were compared with data collected through a previously established methodology utilizing the Crystal 16 multiple reactor system. We report that nucleation in the microfluidic system behaves in a similar manner to other non-agitated systems with different regimes of nucleation kinetics: a nonnucleating regime, a slowly nucleating regime and a fast nucleating regime. As such, this type of data is best fitted to a double exponential curve. This behaviour is not yet fully understood, as agitated systems generally show a single nucleation regime, where induction time data can be fitted by a simple exponential curve. Therefore, it is not straightforward to directly compare nucleation rate obtained under agitated and non-agitated conditions. The microfluidic device presented can be used for non-agitated nucleation rate studies, however, further refinement ofthe design could improve control of crystallization conditions and extend its operational capacity and range
Automation for patient screening
No full textDiagnostic imaging is the gold standard for differential diagnosis of disease, with ultrasound being the second most requested scan after X-ray with more than 8 million ultrasounds performed by NHS England in 2021 accounting for over 20% of all imaging performed. Ultrasound cross sectional imagery is used every day to make critical decisions that could drastically affect patient outcome. While diagnostic ultrasound cross sections are clearly defined within a clinical protocol, the clinician is solely responsible for acquisition and interpretation of ultrasound imagery, with few safeguards against human error.This Canon sponsored EngD looked at the potential of machine learning to standardise processes, reduce burden on users by automating the adherence to protocols, reduce the time required by streamlining workflows, and lower the skill requirement of the clinical user. The initial study was the first to characterise the response of neural networks for the classification of cross sections specified by the Japanese abdominal scanning protocol. This protocol, one of the largest ultrasound protocols ever studied, consists of 16 overlapping cross sectional views of the abdomen, and achieved a classification accuracy of 79.9%. This provided a baseline for a transfer learning study, utilising pre-trained neural networks to increase training efficiency and lead to an increase in accuracy to 83.9%. Small mobile networks were shown to be just as effective at classification of ultrasound at a fraction of the system resources, achieving comparable accuracies of 84.5%. Novel methods of cost reduction were explored to lower the burden of production of datasets for machine learning using power theory and active learning, providing a novel cost-effective framework for data collection and labelling. In order to overcome the limitations of image-based classification, a novel approach of augmenting neural network classification with positional data from lab based positional tracking systems was proposed.Ultrasound and positional data were collected from an abdominal phantom which allowed for the classification of six overlapping and hard to recognise abdominal cross sections with accuracies above 98%. A novel pilot study on 11 soft body Thiel cadavers, further refined this technique by exploring normalisation as a method to reduce the variability of coordinates produced when scanning the abdominal cavity and achieved an accuracy 96.8% using 3 points of normalisation. This work has demonstrated the efficacy of classification of abdominal ultrasound cross sections using neural networks and overcome the accuracy limitations of image-only classification of common ultrasound edge cases using a novel positional tracking approach, that achieved results far exceeding the current industry classification standards of abdominal cross sections.Diagnostic imaging is the gold standard for differential diagnosis of disease, with ultrasound being the second most requested scan after X-ray with more than 8 million ultrasounds performed by NHS England in 2021 accounting for over 20% of all imaging performed. Ultrasound cross sectional imagery is used every day to make critical decisions that could drastically affect patient outcome. While diagnostic ultrasound cross sections are clearly defined within a clinical protocol, the clinician is solely responsible for acquisition and interpretation of ultrasound imagery, with few safeguards against human error.This Canon sponsored EngD looked at the potential of machine learning to standardise processes, reduce burden on users by automating the adherence to protocols, reduce the time required by streamlining workflows, and lower the skill requirement of the clinical user. The initial study was the first to characterise the response of neural networks for the classification of cross sections specified by the Japanese abdominal scanning protocol. This protocol, one of the largest ultrasound protocols ever studied, consists of 16 overlapping cross sectional views of the abdomen, and achieved a classification accuracy of 79.9%. This provided a baseline for a transfer learning study, utilising pre-trained neural networks to increase training efficiency and lead to an increase in accuracy to 83.9%. Small mobile networks were shown to be just as effective at classification of ultrasound at a fraction of the system resources, achieving comparable accuracies of 84.5%. Novel methods of cost reduction were explored to lower the burden of production of datasets for machine learning using power theory and active learning, providing a novel cost-effective framework for data collection and labelling. In order to overcome the limitations of image-based classification, a novel approach of augmenting neural network classification with positional data from lab based positional tracking systems was proposed.Ultrasound and positional data were collected from an abdominal phantom which allowed for the classification of six overlapping and hard to recognise abdominal cross sections with accuracies above 98%. A novel pilot study on 11 soft body Thiel cadavers, further refined this technique by exploring normalisation as a method to reduce the variability of coordinates produced when scanning the abdominal cavity and achieved an accuracy 96.8% using 3 points of normalisation. This work has demonstrated the efficacy of classification of abdominal ultrasound cross sections using neural networks and overcome the accuracy limitations of image-only classification of common ultrasound edge cases using a novel positional tracking approach, that achieved results far exceeding the current industry classification standards of abdominal cross sections
Access Repository Dashboard
Do you manage STAX (Strathclyde Repository)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!