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An application protocol for near net shape technologies implementation
Get PDFThe adoption of innovative Near Net Shape (NNS) manufacturing technologies can dramatically reduce costs and lead times in established manufacturing processes. However identifying candidate NNS processes and optimizing their implementation is frequently done in an adhoc manner without the benefits of a structured process of discovery and assessment. Motivated by the need for more robust assessment of potential NNS applications this thesis presents a methodology for selecting NNS manufacturing technologies and optimizing their implementation in established manufacturing processes. The literature review highlights a lack of systematic methodologies that support a holistic approach to assessing the impact of an NNS process (in terms of machining time and raw material consumption) on an established manufacturing chain. The methodology (known as the Near Net Shape Operative(NeNeShO) Protocol) is a three step pipeline that first creates a short-list of candidate processes, before selecting and, lastly, optimising the operational parameters. The first phase (Product Geometry, Manufacturing and Material Matching (ProGeMa3) is a quantitative methodology that selects a set of viable primary shaping process using a unique form of Process Selection Matrix (ProSMa), that associates processes with a range of materials and product geometry they can shape. ProGeMa3 ranks the candidate processes (using fuzzy logic) by their ability to achieve target product requirements (e.g. tolerances, mechanical properties) in relationship to current process capabilities.;The second phase (Differential Cost and Feasibility Analysis - DFCA) combines technological feasibility (i.e. analytical, numerical or experimental approaches) and economic feasibility (theoretical, statistical derived, analogous cost models) to establish the ability of an NNS process to deliver the specified product requirements. The process models used in phase two are also applied in the third phase (Conditional Design Optimization- CoDeO) and, depending on the selected route, optimization algorithms (e.g. genetic algorithms) or statistical methods (e.g. Design of Experiment) are used to refine the implementation. Case study applications and existing literature have been used to establish the completeness and effectiveness of the NeNeShO methodology. The resulting NNS selection system is believed to be the only quantitative and systematic procedure that can guide both the selection and optimization of feasible NNS processes in the context of an existing process chain.The adoption of innovative Near Net Shape (NNS) manufacturing technologies can dramatically reduce costs and lead times in established manufacturing processes. However identifying candidate NNS processes and optimizing their implementation is frequently done in an adhoc manner without the benefits of a structured process of discovery and assessment. Motivated by the need for more robust assessment of potential NNS applications this thesis presents a methodology for selecting NNS manufacturing technologies and optimizing their implementation in established manufacturing processes. The literature review highlights a lack of systematic methodologies that support a holistic approach to assessing the impact of an NNS process (in terms of machining time and raw material consumption) on an established manufacturing chain. The methodology (known as the Near Net Shape Operative(NeNeShO) Protocol) is a three step pipeline that first creates a short-list of candidate processes, before selecting and, lastly, optimising the operational parameters. The first phase (Product Geometry, Manufacturing and Material Matching (ProGeMa3) is a quantitative methodology that selects a set of viable primary shaping process using a unique form of Process Selection Matrix (ProSMa), that associates processes with a range of materials and product geometry they can shape. ProGeMa3 ranks the candidate processes (using fuzzy logic) by their ability to achieve target product requirements (e.g. tolerances, mechanical properties) in relationship to current process capabilities.;The second phase (Differential Cost and Feasibility Analysis - DFCA) combines technological feasibility (i.e. analytical, numerical or experimental approaches) and economic feasibility (theoretical, statistical derived, analogous cost models) to establish the ability of an NNS process to deliver the specified product requirements. The process models used in phase two are also applied in the third phase (Conditional Design Optimization- CoDeO) and, depending on the selected route, optimization algorithms (e.g. genetic algorithms) or statistical methods (e.g. Design of Experiment) are used to refine the implementation. Case study applications and existing literature have been used to establish the completeness and effectiveness of the NeNeShO methodology. The resulting NNS selection system is believed to be the only quantitative and systematic procedure that can guide both the selection and optimization of feasible NNS processes in the context of an existing process chain
The effect of size and void configuration on the stress intensity factor of regular and stochastic porous materials
Get PDFBoth, naturally occurring and manufactured porous materials, offer unique and attractive properties. Yet, the inclusion of even a small porosity percentage in materials is usually considered a threat to their integrity and strength. Novel manufacturing technologies,like additive manufacturing, are especially likely to introduce a low percentage of porosity on manufactured components. Additionally, such technologies allow for the manufacturing of smaller, more delicate geometries and mesostructures, whose fracture behaviour deviates from the so far accepted theories.The aim of this study is to map the relationship between the mesostructural parameters of low to medium porosity brittle materials and their fracture properties in mode I loading. A multi-parameter investigation was conducted and specimens with different topologies of idealised and probabilistic porosity were considered.Results showed that the use of a single fracture parameter in porous materials is often inadequate. More specifically, prominent size effects were observed, both numerically and experimentally, thereby deviating from the scaling predictions of Linear Elastic Fracture Mechanics under Small Scale Yielding conditions. These deviations are attributed to the loss of K-dominance in the presence of porosity, implying the increased significance of non-singular stresses on the local stress field. Focusing at the scale of the heterogeneity, it was found that each specimen is actually characterised by multiple, local stress intensities, depending on the relative location between the heterogeneity and the crack tip. Design of Experiments was employed to provide insight on how a heterogeneity's location can be designed to either amplify or diminish the stress at the crack tip, thus producing a tailored response.These findings can act as a theoretical framework on which guidelines for the design of bespoke, novel materials can be drawn, so that porosity may no longer be viewed as a defect, but as a means for damage tolerant design, leading to controlled fracture.Both, naturally occurring and manufactured porous materials, offer unique and attractive properties. Yet, the inclusion of even a small porosity percentage in materials is usually considered a threat to their integrity and strength. Novel manufacturing technologies,like additive manufacturing, are especially likely to introduce a low percentage of porosity on manufactured components. Additionally, such technologies allow for the manufacturing of smaller, more delicate geometries and mesostructures, whose fracture behaviour deviates from the so far accepted theories.The aim of this study is to map the relationship between the mesostructural parameters of low to medium porosity brittle materials and their fracture properties in mode I loading. A multi-parameter investigation was conducted and specimens with different topologies of idealised and probabilistic porosity were considered.Results showed that the use of a single fracture parameter in porous materials is often inadequate. More specifically, prominent size effects were observed, both numerically and experimentally, thereby deviating from the scaling predictions of Linear Elastic Fracture Mechanics under Small Scale Yielding conditions. These deviations are attributed to the loss of K-dominance in the presence of porosity, implying the increased significance of non-singular stresses on the local stress field. Focusing at the scale of the heterogeneity, it was found that each specimen is actually characterised by multiple, local stress intensities, depending on the relative location between the heterogeneity and the crack tip. Design of Experiments was employed to provide insight on how a heterogeneity's location can be designed to either amplify or diminish the stress at the crack tip, thus producing a tailored response.These findings can act as a theoretical framework on which guidelines for the design of bespoke, novel materials can be drawn, so that porosity may no longer be viewed as a defect, but as a means for damage tolerant design, leading to controlled fracture
The rational structure-based design of a protein nanoparticle presenting a chimeric MenB antigen
No full textBacterial infection by the gram-negative diplococcus Neisseria meningitidis serogroup B (MenB) is a leading cause of meningitis and septicaemia. Vaccines rank amongst the most important public health interventions for combating these diseases. As vaccine development orientates towards more minimalist subunit antigen-based vaccines, new adjuvant systems are increasingly needed to boost immunogenicity. The application of nanoparticles in vaccine formulations has the potential to drive the development of next generation adjuvant systems that improve antigen presentation and overall vaccine immunogenicity.;In addition, advances in structural and computational biology have enabled a new era of vaccine design and discovery, Structural Vaccinology, which seeks the rational structure-based design of improved vaccine antigens measured in terms of epitope presentation, stability and ease of production. In this project, a structural vaccinology approach is adopted toward the rational design of a self-assembling ferritin nanoparticle system displaying a chimeric protein antigen to stimulate broad and efficacious immunogenicity against MenB.;This chimeric antigen, incorporating epitopes from the NadA3 and PorA MenB antigens seeks to confer broader MenB strain coverage, while its incorporation into a self-assembling ferritin-based nanoparticle system sees the chimeric NadA3-PorA presented in a multicopy format on the ferritin surface, enhancing the immunogenicity. The first part of the thesis describes the in silico design of a feasible protein nanoparticle system using X-ray crystallography data.;This NadA3-PorA-Ferritin was then expressed and purified, before its epitope presentation was characterised by a range of structural and biochemical approaches, including cryo-electron microscopy (cryo-EM). The immunogenicity of the NadA3-PorA-Ferritin was assessed in vivo, revealing that recombinant nanoparticle presentation of the NadA3-PorA enhanced the humoral responses raised against the subunit antigen.;Different adjuvant systems to deliver the NadA3-PorA-Ferritin were also examined, demonstrating that an in-house, cationic liposome formulation produced by benchtop microfluidics generated a similar level of immunogenicity as a commercially available MF59-based emulsion adjuvant. Further serological assays were performed to gauge the bactericidal titre resulting from immunisation with the nanoparticle. The work within this project exemplifies a structural vaccinology approach towards the design of a chimeric protein antigen-presenting self-assembling nanoparticle system that is able to confer broad and efficacious protection against MenB.Bacterial infection by the gram-negative diplococcus Neisseria meningitidis serogroup B (MenB) is a leading cause of meningitis and septicaemia. Vaccines rank amongst the most important public health interventions for combating these diseases. As vaccine development orientates towards more minimalist subunit antigen-based vaccines, new adjuvant systems are increasingly needed to boost immunogenicity. The application of nanoparticles in vaccine formulations has the potential to drive the development of next generation adjuvant systems that improve antigen presentation and overall vaccine immunogenicity.;In addition, advances in structural and computational biology have enabled a new era of vaccine design and discovery, Structural Vaccinology, which seeks the rational structure-based design of improved vaccine antigens measured in terms of epitope presentation, stability and ease of production. In this project, a structural vaccinology approach is adopted toward the rational design of a self-assembling ferritin nanoparticle system displaying a chimeric protein antigen to stimulate broad and efficacious immunogenicity against MenB.;This chimeric antigen, incorporating epitopes from the NadA3 and PorA MenB antigens seeks to confer broader MenB strain coverage, while its incorporation into a self-assembling ferritin-based nanoparticle system sees the chimeric NadA3-PorA presented in a multicopy format on the ferritin surface, enhancing the immunogenicity. The first part of the thesis describes the in silico design of a feasible protein nanoparticle system using X-ray crystallography data.;This NadA3-PorA-Ferritin was then expressed and purified, before its epitope presentation was characterised by a range of structural and biochemical approaches, including cryo-electron microscopy (cryo-EM). The immunogenicity of the NadA3-PorA-Ferritin was assessed in vivo, revealing that recombinant nanoparticle presentation of the NadA3-PorA enhanced the humoral responses raised against the subunit antigen.;Different adjuvant systems to deliver the NadA3-PorA-Ferritin were also examined, demonstrating that an in-house, cationic liposome formulation produced by benchtop microfluidics generated a similar level of immunogenicity as a commercially available MF59-based emulsion adjuvant. Further serological assays were performed to gauge the bactericidal titre resulting from immunisation with the nanoparticle. The work within this project exemplifies a structural vaccinology approach towards the design of a chimeric protein antigen-presenting self-assembling nanoparticle system that is able to confer broad and efficacious protection against MenB
Terpenoid inhibition of DsbA : a periplasmic protein from the dysentery-causing bacterium, Shigella sonnei
Get PDFA major challenge faced by modern medicine is antimicrobial resistance that has become a major problem in recent year. As such, there is a requirement for the introduction of alternative approaches to treat infections of multi-resistant strains of bacillary dysentery-caused by Shigella sonnei. DsbA is a disulphide bond oxidoreductase enzyme and is a major contributor to virulence in S. sonnei. It is a periplasmic protein required for Shigella survival in the host cell cytosol. DsbA is found in all Gram-negative and some Gram-positive bacteria, therefore, targeting DsbA is a logical strategy to treat dysentery-causing Shigella. Here we show that terpenoids, natural substances present in the essential oils of plants, can reduce S.sonnei proliferation inside host cells. Terpenoids exert little cytotoxicity on the cell lines and protected Galleria mellonella larvae from killing by S. sonnei. Geraniol was the most potent compound from the twelve terpenoids tested in this study. In addition, the study confirmed that DsbA is vital for S. sonnei to survive and proliferate in a reducing environment. Geraniol was able to reduce the activity of purified DsbA protein on reduction of Di-E-GSSG in an in vitro assay. Importantly, this study also showed that S. sonnei could catalyse E-GSH conversion to Di-E-GSSG through DsbA activity. This finding explained for the first time a novel mechanism used by S. sonneiin recycling non-functional reduced DsbA to its functional oxidised form. Moreover, geraniol was also able to inhibit the catalysis of E-GSH to around half of the wild type DsbA activity in S. sonnei. Geraniol became completely inactive when its interaction sites were substituted on DsbA, and it was unable to protect Galleria mellonella from killing by S. sonnei dsbA mutants. These findings suggest that geraniol holds a great therapeutic potential against Shigella infection.A major challenge faced by modern medicine is antimicrobial resistance that has become a major problem in recent year. As such, there is a requirement for the introduction of alternative approaches to treat infections of multi-resistant strains of bacillary dysentery-caused by Shigella sonnei. DsbA is a disulphide bond oxidoreductase enzyme and is a major contributor to virulence in S. sonnei. It is a periplasmic protein required for Shigella survival in the host cell cytosol. DsbA is found in all Gram-negative and some Gram-positive bacteria, therefore, targeting DsbA is a logical strategy to treat dysentery-causing Shigella. Here we show that terpenoids, natural substances present in the essential oils of plants, can reduce S.sonnei proliferation inside host cells. Terpenoids exert little cytotoxicity on the cell lines and protected Galleria mellonella larvae from killing by S. sonnei. Geraniol was the most potent compound from the twelve terpenoids tested in this study. In addition, the study confirmed that DsbA is vital for S. sonnei to survive and proliferate in a reducing environment. Geraniol was able to reduce the activity of purified DsbA protein on reduction of Di-E-GSSG in an in vitro assay. Importantly, this study also showed that S. sonnei could catalyse E-GSH conversion to Di-E-GSSG through DsbA activity. This finding explained for the first time a novel mechanism used by S. sonneiin recycling non-functional reduced DsbA to its functional oxidised form. Moreover, geraniol was also able to inhibit the catalysis of E-GSH to around half of the wild type DsbA activity in S. sonnei. Geraniol became completely inactive when its interaction sites were substituted on DsbA, and it was unable to protect Galleria mellonella from killing by S. sonnei dsbA mutants. These findings suggest that geraniol holds a great therapeutic potential against Shigella infection
Stochastic modelling of nutrient and predator-prey populations
Get PDFThis thesis first constructs a stochastic differential equation (SDE) model of a fjord nutrient, based on the hydrographic and chemical data collected from the 1991 field campaign implemented in Loch Linnhe. Stochastic modelling approach is able to account for the process noise in the nutrient data. The SDE model is first extended from a deterministic nutrient model by the parameter perturbation scheme.;To capture the annual variations in the sea-loch nutrient, the SDE model is refined by considering the complex physical and biological processes that make big effects on the nutrient dynamics. The model is parameterised using the least squares approach. The goodness of fit of the SDE model is assessed by comparing the distribution graphs and by performing statistical tests. The existence of the environmental-type process noise in the nutrient data is illustrated by a residual analysis for the data. Finally a simulation study is carried out to identify the accuracy of the parameter estimation frameworks.;This thesis also studies the stochastic versions of the foraging arena predator-prey system. The impacts of different types of environmental noise on the population dynamics are deduced. First of all, the SDE predator-prey model is formulated by incorporating white noise into the deterministic foraging arena system using the parameter perturbation technique. We then prove that the SDE has a unique global positive solution. We also study the asymptotic moment estimate of the model solution and produce the conditions for the system to be extinct.;Furthermore the existence of a stationary distribution is pointed out under certain parametric restrictions. Secondly of all, we take a further step of incorporating telegraph noise and time delay to the stochastic foraging arena system. The stochastically ultimate boundedness, extinction and the pathwise estimation of the population system are studied. Thirdly, we introduce white noise to more system parameters since all of them can be inuenced by the complex variability.;Namely, not only the growth rate of prey and the density-dependent mortality rate of predator, but also the quadratic mortality rates of the two species and the capturing rate of predator are perturbed by the stochastic noise. Then we study how the correlations between the Brownian motions affect the long-time properties of the system. The parametric conditions for the system to have a stationary distribution are deduced. Numerical simulations are carried out to substantiate the analytical results.This thesis first constructs a stochastic differential equation (SDE) model of a fjord nutrient, based on the hydrographic and chemical data collected from the 1991 field campaign implemented in Loch Linnhe. Stochastic modelling approach is able to account for the process noise in the nutrient data. The SDE model is first extended from a deterministic nutrient model by the parameter perturbation scheme.;To capture the annual variations in the sea-loch nutrient, the SDE model is refined by considering the complex physical and biological processes that make big effects on the nutrient dynamics. The model is parameterised using the least squares approach. The goodness of fit of the SDE model is assessed by comparing the distribution graphs and by performing statistical tests. The existence of the environmental-type process noise in the nutrient data is illustrated by a residual analysis for the data. Finally a simulation study is carried out to identify the accuracy of the parameter estimation frameworks.;This thesis also studies the stochastic versions of the foraging arena predator-prey system. The impacts of different types of environmental noise on the population dynamics are deduced. First of all, the SDE predator-prey model is formulated by incorporating white noise into the deterministic foraging arena system using the parameter perturbation technique. We then prove that the SDE has a unique global positive solution. We also study the asymptotic moment estimate of the model solution and produce the conditions for the system to be extinct.;Furthermore the existence of a stationary distribution is pointed out under certain parametric restrictions. Secondly of all, we take a further step of incorporating telegraph noise and time delay to the stochastic foraging arena system. The stochastically ultimate boundedness, extinction and the pathwise estimation of the population system are studied. Thirdly, we introduce white noise to more system parameters since all of them can be inuenced by the complex variability.;Namely, not only the growth rate of prey and the density-dependent mortality rate of predator, but also the quadratic mortality rates of the two species and the capturing rate of predator are perturbed by the stochastic noise. Then we study how the correlations between the Brownian motions affect the long-time properties of the system. The parametric conditions for the system to have a stationary distribution are deduced. Numerical simulations are carried out to substantiate the analytical results
A sociological account of the introduction of the offensive behaviour at football and threatening communications (Scotland) act 2012 and how it was utilised by police officers in the Scottish football environment
Get PDFThis thesis sets out a broad sociological narrative of the introduction of the Offensive Behaviour at Football and Threatening Communication (Scotland) Act 2012 and how it was implemented and utilised by the police in Scotland prior to its repeal in 2018. The legislation was introduced with some haste into a specific and significant popular Scottish cultural landscape where distinct and often competing social, political and cultural identities exist and where the phenomenon of "sectarianism", the legislation's primary target, is widely recognised but ill-defined and deeply contested.Lipsky's concept of Street Level Bureaucracy (SLBT), which argues that front line public-sector workers such as the police enjoy high levels of discretion and autonomy and so can actively create new policy through the reality of their interactions with members of the public, is utilised to examine and describe interactions between supporters and officers in this context and also to test the continued relevance of SLBT in such a setting.The thesis argues that SLBT remains relevant in describing police behaviours however whilst officers retain the ability to exercise high levels of discretion in the football environment this is influenced by temporal and spatial factors. In particular increased methods of surveillance such as CCTV has reduced the areas of "low visibility" where street level interactions occur, thereby decreasing the exercise of discretion by officers.Furthermore, whilst the research finds clear evidence of individual deviations from stated rules and regulations and that often what occurs in practice does not always reflect the intention of the higher commanders, particularly in relation to "Zero Tolerance" rhetoric, there is insufficient evidence to conclude that such behaviour of officers on the ground amounts to new "policy".This thesis sets out a broad sociological narrative of the introduction of the Offensive Behaviour at Football and Threatening Communication (Scotland) Act 2012 and how it was implemented and utilised by the police in Scotland prior to its repeal in 2018. The legislation was introduced with some haste into a specific and significant popular Scottish cultural landscape where distinct and often competing social, political and cultural identities exist and where the phenomenon of "sectarianism", the legislation's primary target, is widely recognised but ill-defined and deeply contested.Lipsky's concept of Street Level Bureaucracy (SLBT), which argues that front line public-sector workers such as the police enjoy high levels of discretion and autonomy and so can actively create new policy through the reality of their interactions with members of the public, is utilised to examine and describe interactions between supporters and officers in this context and also to test the continued relevance of SLBT in such a setting.The thesis argues that SLBT remains relevant in describing police behaviours however whilst officers retain the ability to exercise high levels of discretion in the football environment this is influenced by temporal and spatial factors. In particular increased methods of surveillance such as CCTV has reduced the areas of "low visibility" where street level interactions occur, thereby decreasing the exercise of discretion by officers.Furthermore, whilst the research finds clear evidence of individual deviations from stated rules and regulations and that often what occurs in practice does not always reflect the intention of the higher commanders, particularly in relation to "Zero Tolerance" rhetoric, there is insufficient evidence to conclude that such behaviour of officers on the ground amounts to new "policy"
Development of novel allosteric regulators of proteinase-activated receptors
Get PDFProteinase-activated receptors (PARs), members of the G-protein coupled receptor (GPCR) superfamily of proteins, represent highly attractive targets for therapy across a wide range of diseases. Of specific interest are PAR1 and PAR2, the major signalling members of the PAR family which are associated with cardiovascular disease, cancer and inflammatory disease. However, despite significant efforts, there is only one marketed drug for the PARs available in Vorapaxar, which is used to inhibit PAR1 in the treatment of thrombosis. Thus, exploring different chemical approaches to developing better lead molecules is important to explore novel methods for modulating the PARs. Pepducins, peptidic compounds containing a palmitoyl chain, have represented a novel approach to allosteric modulation of PARs, with PZ-128 targeting PAR1 and PZ-235 targeting PAR2 as promising lead compounds. However, deviation from the general pepducin structure has not been explored and represent possible areas of improvement. Herein, 10 novel PZ-128 analogues are described as potential improvements to PZ-128 highlighting the impact of linker modification as well as cyclisation of the peptide sequence. Additionally, off-target activity of PZ-128 is also explored, highlighting some intrinsic problems with the pepducin approach. These problems were alleviated to an extent with the novel PZ-128 analogues but identifying overall improvements to the pharmacological character of the series proved challenging. Recently, two potential lead molecules were published targeting PAR2 with AZ8838 and AZ3451. These compounds have provided new insight into how we can target PAR2, allowing access to novel chemicals with improved properties. Through a series of modifications to the published chemical structures, we have accessed novel compounds that display similar biological properties to AZ8838. Herein, 15 novel analogues of AZ8838 have been synthesised and their propensity for PAR2 inhibition tested in in vitro assays, identifying one compound of comparable potency whilst exploring the SAR surrounding the AZ8838 binding pocket. Additionally, an expanded library of AZ8838 analogues has been computationally docked to assess binding within PAR2 in silico.Proteinase-activated receptors (PARs), members of the G-protein coupled receptor (GPCR) superfamily of proteins, represent highly attractive targets for therapy across a wide range of diseases. Of specific interest are PAR1 and PAR2, the major signalling members of the PAR family which are associated with cardiovascular disease, cancer and inflammatory disease. However, despite significant efforts, there is only one marketed drug for the PARs available in Vorapaxar, which is used to inhibit PAR1 in the treatment of thrombosis. Thus, exploring different chemical approaches to developing better lead molecules is important to explore novel methods for modulating the PARs. Pepducins, peptidic compounds containing a palmitoyl chain, have represented a novel approach to allosteric modulation of PARs, with PZ-128 targeting PAR1 and PZ-235 targeting PAR2 as promising lead compounds. However, deviation from the general pepducin structure has not been explored and represent possible areas of improvement. Herein, 10 novel PZ-128 analogues are described as potential improvements to PZ-128 highlighting the impact of linker modification as well as cyclisation of the peptide sequence. Additionally, off-target activity of PZ-128 is also explored, highlighting some intrinsic problems with the pepducin approach. These problems were alleviated to an extent with the novel PZ-128 analogues but identifying overall improvements to the pharmacological character of the series proved challenging. Recently, two potential lead molecules were published targeting PAR2 with AZ8838 and AZ3451. These compounds have provided new insight into how we can target PAR2, allowing access to novel chemicals with improved properties. Through a series of modifications to the published chemical structures, we have accessed novel compounds that display similar biological properties to AZ8838. Herein, 15 novel analogues of AZ8838 have been synthesised and their propensity for PAR2 inhibition tested in in vitro assays, identifying one compound of comparable potency whilst exploring the SAR surrounding the AZ8838 binding pocket. Additionally, an expanded library of AZ8838 analogues has been computationally docked to assess binding within PAR2 in silico
An evaluation of ground pipe ventilation and overnight radiant cooling to displace air conditioning in Nigeria
Get PDFStimulating minimal energy use and a consequential reduction in CO2 emissions to curb global warming has been a great challenge for mankind particularly when more than half of all prime energy supplied is consumed by the built environment. In Nigeria, 44% of primary energy consumption is used by the built environment with 75% of this used for air conditioning. To compensate for regular power outages in the Nigerian electricity supply system, 80% of households also operate independent electricity generators, primarily to maintain mechanical cooling and food preservation. Energy consumption is expected to rise as most new buildings don ot incorporate any significant energy saving techniques that could reduce cooling demands. Providing a solution to this becomes a major challenge for architects and the building industry in Nigeria.;Factors such as pollution, insects, high dust levels and home security, negatively impact on the use of natural ventilation techniques which is a common practice, with most home owners keeping windows permanently closed, increasing their dependence on mechanical means of cooling to maintain indoor comfort. The task is therefore to develop sustainable cooling strategies for buildings in this region without compromising indoor air quality and security. The research assessed and analysed the thermo physical properties and energy performance of existing building types and developed an enhanced 'fabric first' solution followed by a synergised application of ground pipe supply ventilation and cool air supply due to clear night sky radiation from roof mounted black body as passive cooling techniques for buildings in South Eastern Nigeria.;Despite the thermal interfaces being less than optimal, the results suggest that the application of such passive cooling strategies in combination with enhanced building fabric using thermal inertia and external insulation, can displace circa 83.5% of energy demand for domestic air conditioning. This could - in the long term - reduce energy consumption in the building sector from 44% to 16.45 %, with a commensurate reduction in the carbon footprint. The energy saving costs in use, were calculated to offset the additional capital costs, in under 8 years. These strategies and techniques are therefore worth further investigation as they represent both an economic and environmental gain.Stimulating minimal energy use and a consequential reduction in CO2 emissions to curb global warming has been a great challenge for mankind particularly when more than half of all prime energy supplied is consumed by the built environment. In Nigeria, 44% of primary energy consumption is used by the built environment with 75% of this used for air conditioning. To compensate for regular power outages in the Nigerian electricity supply system, 80% of households also operate independent electricity generators, primarily to maintain mechanical cooling and food preservation. Energy consumption is expected to rise as most new buildings don ot incorporate any significant energy saving techniques that could reduce cooling demands. Providing a solution to this becomes a major challenge for architects and the building industry in Nigeria.;Factors such as pollution, insects, high dust levels and home security, negatively impact on the use of natural ventilation techniques which is a common practice, with most home owners keeping windows permanently closed, increasing their dependence on mechanical means of cooling to maintain indoor comfort. The task is therefore to develop sustainable cooling strategies for buildings in this region without compromising indoor air quality and security. The research assessed and analysed the thermo physical properties and energy performance of existing building types and developed an enhanced 'fabric first' solution followed by a synergised application of ground pipe supply ventilation and cool air supply due to clear night sky radiation from roof mounted black body as passive cooling techniques for buildings in South Eastern Nigeria.;Despite the thermal interfaces being less than optimal, the results suggest that the application of such passive cooling strategies in combination with enhanced building fabric using thermal inertia and external insulation, can displace circa 83.5% of energy demand for domestic air conditioning. This could - in the long term - reduce energy consumption in the building sector from 44% to 16.45 %, with a commensurate reduction in the carbon footprint. The energy saving costs in use, were calculated to offset the additional capital costs, in under 8 years. These strategies and techniques are therefore worth further investigation as they represent both an economic and environmental gain
Career experiences of Kenyan migrant hotel workers in the UK hotel sector
Get PDFGlobalisation has led to many people moving from one country to another. The service sector, particularly the hosptiality and tourism sector is considered labour-intensive, therefore, acts as magnet for migrant labour and as such, is largely reliant on marginal workers. Furthermore, the hospitality industry is often used as an entry to the labour market, and finds itself as a large employer of migrant workers. However, the industry lies in the secondary labour market which is characterised by low wages, poor training, low unionisation, and general poor working conditions.Nevertheless, a career in the hospitality and tourism sector is often considered vibrant unlike in the western context. In the Kenyan context, workers undego a rigorous training, equipping them to work not only for their country but globally. Thus, the low-skill perception of the hospitality sector in the west, presents inconsistency in the labour market for a skilled workforce with the desire to pursue a career in the industry.;As such, skilled Kenyan hotel migrant workers are faced with the limitations to progress their hotel career abroad. The presence of structural factors limits migrants' career mobility in the host country resulting in underemployment and a degradation of their skills in advanced economies, such as the UK. construed as career loss.In evaluating the empirical evidence of the skilled Kenyan hotel migrant wokers, concepts have been employed to develop a framework for the understanding of complex intersection of a number of inter-related themes that include, inter alia, economic migration, migrant professional and social integration, motives for migrants to leave or stay in their host country and occupational underemployment, thereby contributing to migrant labour literature.Globalisation has led to many people moving from one country to another. The service sector, particularly the hosptiality and tourism sector is considered labour-intensive, therefore, acts as magnet for migrant labour and as such, is largely reliant on marginal workers. Furthermore, the hospitality industry is often used as an entry to the labour market, and finds itself as a large employer of migrant workers. However, the industry lies in the secondary labour market which is characterised by low wages, poor training, low unionisation, and general poor working conditions.Nevertheless, a career in the hospitality and tourism sector is often considered vibrant unlike in the western context. In the Kenyan context, workers undego a rigorous training, equipping them to work not only for their country but globally. Thus, the low-skill perception of the hospitality sector in the west, presents inconsistency in the labour market for a skilled workforce with the desire to pursue a career in the industry.;As such, skilled Kenyan hotel migrant workers are faced with the limitations to progress their hotel career abroad. The presence of structural factors limits migrants' career mobility in the host country resulting in underemployment and a degradation of their skills in advanced economies, such as the UK. construed as career loss.In evaluating the empirical evidence of the skilled Kenyan hotel migrant wokers, concepts have been employed to develop a framework for the understanding of complex intersection of a number of inter-related themes that include, inter alia, economic migration, migrant professional and social integration, motives for migrants to leave or stay in their host country and occupational underemployment, thereby contributing to migrant labour literature
Insights into the Function on the Knee Meniscus
Get PDFThe knee menisci are understood to have a variety of roles including load transmission and stability of the knee joint. To date, there has been no exploration of the role of radial tears of the menisci in inducing kinematic changes in knee joint movement. Furthermore, the function of proteoglycans in maintaining mechanical meniscus has not been explored.Load was applied to cadaveric knees in the intact state and following both a 50% and 100% radial tear of the medial (5 knees) or lateral (6 knees) meniscus. A coordinate system was developed to allow analysis of joint kinematics. Concurrently,confined compression techniques were used to apply 10% strain to meniscal samples from cadavers (30 samples) and patients suffering osteoarthritis (36 samples) in solutions of varying ionic concentration. 7 samples from an Actifit meniscal scaffold were also tested in deionised water. Resultant relaxation curves were fit using finite element modelling techniques. Human tissue samples were assayed for proteoglycan content.Radial tears of the meniscus did not induce significant changes in knee joint kinematics.Finite element modelling demonstrated that the electrostatic effect of proteoglycans contributed to ~40% of the stiffness of the meniscus. No significant difference in proteoglycan content was observed between solutions. The Actifit meniscal scaffold is stiffer than native meniscal tissue but displays similar permeability.Although radial tears do not alter the kinematics of the knee joint, there is evidence they result in abnormal loading of articular cartilage and it is hence important that they are repaired where possible. Proteoglycans play a critical role in maintaining stiffness of the meniscus - current repair strategies such as meniscal scaffolds do not attempt to recreate this function and hence may not prevent cartilage degradation. The stiffness of the Actifit meniscal scaffold may help protect a nascent meniscal repair but may also contribute to abnormal joint loading; its similar permeability will help mimic meniscal function.The knee menisci are understood to have a variety of roles including load transmission and stability of the knee joint. To date, there has been no exploration of the role of radial tears of the menisci in inducing kinematic changes in knee joint movement. Furthermore, the function of proteoglycans in maintaining mechanical meniscus has not been explored.Load was applied to cadaveric knees in the intact state and following both a 50% and 100% radial tear of the medial (5 knees) or lateral (6 knees) meniscus. A coordinate system was developed to allow analysis of joint kinematics. Concurrently,confined compression techniques were used to apply 10% strain to meniscal samples from cadavers (30 samples) and patients suffering osteoarthritis (36 samples) in solutions of varying ionic concentration. 7 samples from an Actifit meniscal scaffold were also tested in deionised water. Resultant relaxation curves were fit using finite element modelling techniques. Human tissue samples were assayed for proteoglycan content.Radial tears of the meniscus did not induce significant changes in knee joint kinematics.Finite element modelling demonstrated that the electrostatic effect of proteoglycans contributed to ~40% of the stiffness of the meniscus. No significant difference in proteoglycan content was observed between solutions. The Actifit meniscal scaffold is stiffer than native meniscal tissue but displays similar permeability.Although radial tears do not alter the kinematics of the knee joint, there is evidence they result in abnormal loading of articular cartilage and it is hence important that they are repaired where possible. Proteoglycans play a critical role in maintaining stiffness of the meniscus - current repair strategies such as meniscal scaffolds do not attempt to recreate this function and hence may not prevent cartilage degradation. The stiffness of the Actifit meniscal scaffold may help protect a nascent meniscal repair but may also contribute to abnormal joint loading; its similar permeability will help mimic meniscal function
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