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Self-assembling silk hydrogels as a mesenchymal stem cell support matrix for stroke
Get PDFAdvanced cell therapies require robust delivery materials, and silk is a promising contender. This biopolymer already has a long clinical track record and can be assembled into a range of material formats, including hydrogels (Chapter 1). The hypothesis of this thesis was that reverse engineered silk could be programmed to form a self-assembling silk hydrogel for stem cell delivery.;Therefore, the aim of this thesis was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix for stroke treatment. Sonication energy was used to programme the transition of the silk (1 to 5% w/v) secondary structure from a random coil to a stable β-sheet configuration (Chapter 3). This allowed the fine tuning of self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling (Chapter 3) and to support uniform cell distribution as well as cell viability (Chapter 4).;Embedded cells underwent significant proliferation over 14 days, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs showed significantly better viability after injection through a 30G needle when the gels were in the pre-gelled state versus post-gelled state (Chapter 4). Silk hydrogels with physical characteristics that matched those of brain tissue showed good space conformity after stereotaxic injection into an ischaemic stroke lesion in mice (Chapter 5).;Overall, this thesis demonstrates that silk hydrogel is a promising cell delivery (MSC) platform for central nervous system diseases, especially stroke.Advanced cell therapies require robust delivery materials, and silk is a promising contender. This biopolymer already has a long clinical track record and can be assembled into a range of material formats, including hydrogels (Chapter 1). The hypothesis of this thesis was that reverse engineered silk could be programmed to form a self-assembling silk hydrogel for stem cell delivery.;Therefore, the aim of this thesis was to optimise self-assembling silk hydrogels as a mesenchymal stem cell (MSC)-support matrix for stroke treatment. Sonication energy was used to programme the transition of the silk (1 to 5% w/v) secondary structure from a random coil to a stable β-sheet configuration (Chapter 3). This allowed the fine tuning of self-assembling silk hydrogels to achieve space conformity in the absence of any silk hydrogel swelling (Chapter 3) and to support uniform cell distribution as well as cell viability (Chapter 4).;Embedded cells underwent significant proliferation over 14 days, with the best proliferation achieved with 2% w/v hydrogels. Embedded MSCs showed significantly better viability after injection through a 30G needle when the gels were in the pre-gelled state versus post-gelled state (Chapter 4). Silk hydrogels with physical characteristics that matched those of brain tissue showed good space conformity after stereotaxic injection into an ischaemic stroke lesion in mice (Chapter 5).;Overall, this thesis demonstrates that silk hydrogel is a promising cell delivery (MSC) platform for central nervous system diseases, especially stroke
Phytochemical studies on natural products and their biological activities against Trypanosoma
Get PDFThe therapeutic properties of plants have been recognised since the earliest human communities. One plant considered to have biological effects is Holy Basil (Ocimum sanctum L.), with pre-clinical screening uncovering many compounds with effects against bacteria, anaphylaxis, histamines, and diabetes as well as with wound healing and radio-protective effects, including eugenol, euginal, ursolic acid, carvacrol, linalool, limatrol, and caryophyllene. The phytochemistry of this plant is studied in the first section of this thesis.;Propolis is also receiving ample attention in the context of initiatives to discover novel drugs, thanks to its biological and pharmacological qualities. A resinous substance, propolis is produced by honeybees from different plant materials. Different biological effects have been allocated to propolis extracts by earlier studies and their phytoconstituents have been extensively characterised, especially flavonoids, polyphenols, phenolic aldehydes, sesquiterpene quinines, coumarins, amino acids, steroids and inorganic compounds.;The present study employed high-resolution LC-MS, HPLC-ELSD and NMR profiling to analyse the chemical composition of Holy Basil (Ocimum sanctum L.) and a range of types of propolis from various geographical areas. Subsequently, suitable methods of extraction, fractionation and identification were be employed to isolate and identify compounds. Furthermore, one-dimensional and two-dimensional NMR as well as LCMS will be applied to elucidate the structures of the isolated compounds.;A range of compounds were isolated from Holy Basil extracts and different types of propolis by employing various phytochemical methods, including VLC, CC, SEC, preparative TLC.;All crudes extracts, fractions as well as 12 isolated compounds then were subjected for biological testing against Trypanosoma, T. brucei S427 WT, and their cytotoxicity against mammalian cells was also determined. The Holy Basil MeOH extract yielded three pure compounds which were testesd against Trypanosoma, T. brucei S427 WT for the first time and scored relatively moderate to weak activity. While the ethanolic extracts of different types of propolis yielded nine pure compounds.;Three of themwere isolated for the first time from Philippine propolis and yelided against Trypanosoma, T. brucei S427 WT relatively moderate acitivity. The other pure compoundes were isolated from Saudi, red Nigerian and red Brazilian, two pures per each sample, gave as well relatively moderate acitivity. Red Nigerian and red Brazilian showed a high degree of similarity in pures obtained from them.The therapeutic properties of plants have been recognised since the earliest human communities. One plant considered to have biological effects is Holy Basil (Ocimum sanctum L.), with pre-clinical screening uncovering many compounds with effects against bacteria, anaphylaxis, histamines, and diabetes as well as with wound healing and radio-protective effects, including eugenol, euginal, ursolic acid, carvacrol, linalool, limatrol, and caryophyllene. The phytochemistry of this plant is studied in the first section of this thesis.;Propolis is also receiving ample attention in the context of initiatives to discover novel drugs, thanks to its biological and pharmacological qualities. A resinous substance, propolis is produced by honeybees from different plant materials. Different biological effects have been allocated to propolis extracts by earlier studies and their phytoconstituents have been extensively characterised, especially flavonoids, polyphenols, phenolic aldehydes, sesquiterpene quinines, coumarins, amino acids, steroids and inorganic compounds.;The present study employed high-resolution LC-MS, HPLC-ELSD and NMR profiling to analyse the chemical composition of Holy Basil (Ocimum sanctum L.) and a range of types of propolis from various geographical areas. Subsequently, suitable methods of extraction, fractionation and identification were be employed to isolate and identify compounds. Furthermore, one-dimensional and two-dimensional NMR as well as LCMS will be applied to elucidate the structures of the isolated compounds.;A range of compounds were isolated from Holy Basil extracts and different types of propolis by employing various phytochemical methods, including VLC, CC, SEC, preparative TLC.;All crudes extracts, fractions as well as 12 isolated compounds then were subjected for biological testing against Trypanosoma, T. brucei S427 WT, and their cytotoxicity against mammalian cells was also determined. The Holy Basil MeOH extract yielded three pure compounds which were testesd against Trypanosoma, T. brucei S427 WT for the first time and scored relatively moderate to weak activity. While the ethanolic extracts of different types of propolis yielded nine pure compounds.;Three of themwere isolated for the first time from Philippine propolis and yelided against Trypanosoma, T. brucei S427 WT relatively moderate acitivity. The other pure compoundes were isolated from Saudi, red Nigerian and red Brazilian, two pures per each sample, gave as well relatively moderate acitivity. Red Nigerian and red Brazilian showed a high degree of similarity in pures obtained from them
A numerical study on the effect of bow flare angle on green water loading on FPSO
Get PDFWhen there are the strong waves, green water phenomenon has a number of negative effects on ship or floating structures such as damaging structures on the deck and degrading the stability of the ship. Floating production storage and offloading vessels (FPSO) are commonly operated at a certain position and located to encounter mainly bow waves for the purpose of a decrease in roll motions.;This study is focused on the analysis of the effects of the bow flare angle above the free surface on the hydrodynamic loads associated with the green water phenomenon.;When designing the bow flare angle of the FPSO considering the influence of the green water, it is very important to understand the amount of the green water and the impact load on the superstructure on the deck. These are the functions of the bow flare angle of the FPSO as well as the freeboard exceedance level.;Firstly, this study discusses the water level on the deck. Then the flow velocities on the deck are presented. And the pressure on the deck is also considered. Finally, a method of determining green water impacts on structures on the deck is presented. For these four sections, the relation with the wave height and wave period level are given.When there are the strong waves, green water phenomenon has a number of negative effects on ship or floating structures such as damaging structures on the deck and degrading the stability of the ship. Floating production storage and offloading vessels (FPSO) are commonly operated at a certain position and located to encounter mainly bow waves for the purpose of a decrease in roll motions.;This study is focused on the analysis of the effects of the bow flare angle above the free surface on the hydrodynamic loads associated with the green water phenomenon.;When designing the bow flare angle of the FPSO considering the influence of the green water, it is very important to understand the amount of the green water and the impact load on the superstructure on the deck. These are the functions of the bow flare angle of the FPSO as well as the freeboard exceedance level.;Firstly, this study discusses the water level on the deck. Then the flow velocities on the deck are presented. And the pressure on the deck is also considered. Finally, a method of determining green water impacts on structures on the deck is presented. For these four sections, the relation with the wave height and wave period level are given
Development and evaluation of portable passive and real-time measurement systems, and dispersion models, to estimate exposure to traffic-related air pollutants
Get PDFThis research developed efficient applications of portable measurement systems to assess human exposure to traffic-related air pollution through direct measurement, and evaluation of exposure models.Passive NO₂ samplers are deployed at large numbers of sites in epidemiological studies to estimate typical concentrations over 1-4 weeks. I found that deployment time could be reduced to 2 days with limited impact on the accuracy and precision of exposure estimates. This shorter measurement time enabled observation of wind-speed effects leading to overestimation of ambient concentrations by passive samplers. Through development of a post-processing technique and/or inclusion of a membrane I improved sampler accuracy. Portable sensors can provide detailed estimates of personal exposures to air pollution. Many sensor-based monitors have not been subject to rigorous testing procedures to quantify their accuracy. I observed that the most accurate estimates of concentrations from NO₂ and O3 sensor-based monitors required regular, intermittent calibration against reference analysers under similar environmental conditions to field measurements. I also found deterioration in BC monitor accuracy and precison when the attenuation of the collection filter exceeded 40 and no improvement in monitor accuracy was observed when filter darkness correction algorithms were applied. Portable sensors can be used to identify locations with higher concentrations, which may require more detailed monitoring. I established that repeated 6-minute measurements of BC and particle number concentrations estimated similar spatial trends to 1-week NO₂ measurements using passive samplers. Dispersion models can be used to estimate pollution exposure at multiple locations over a study area. I found that initial user parameterisation in a weather model had limited effect on pollution estimates from a dispersion model. I evaluated a new GIS-based dispersion model (5 x 5 m NO₂ estimates for a 3,500 km² area, with model run times of under 10 minutes). I demonstrated that inclusion of discrete street canyon models and geospatial surrogates (accounting for urban morphology) improved model accuracy. The measurement and modelling evaluation research in this thesis complimented each other by providing efficient ways to directly measure population exposures.This research developed efficient applications of portable measurement systems to assess human exposure to traffic-related air pollution through direct measurement, and evaluation of exposure models.Passive NO₂ samplers are deployed at large numbers of sites in epidemiological studies to estimate typical concentrations over 1-4 weeks. I found that deployment time could be reduced to 2 days with limited impact on the accuracy and precision of exposure estimates. This shorter measurement time enabled observation of wind-speed effects leading to overestimation of ambient concentrations by passive samplers. Through development of a post-processing technique and/or inclusion of a membrane I improved sampler accuracy. Portable sensors can provide detailed estimates of personal exposures to air pollution. Many sensor-based monitors have not been subject to rigorous testing procedures to quantify their accuracy. I observed that the most accurate estimates of concentrations from NO₂ and O3 sensor-based monitors required regular, intermittent calibration against reference analysers under similar environmental conditions to field measurements. I also found deterioration in BC monitor accuracy and precison when the attenuation of the collection filter exceeded 40 and no improvement in monitor accuracy was observed when filter darkness correction algorithms were applied. Portable sensors can be used to identify locations with higher concentrations, which may require more detailed monitoring. I established that repeated 6-minute measurements of BC and particle number concentrations estimated similar spatial trends to 1-week NO₂ measurements using passive samplers. Dispersion models can be used to estimate pollution exposure at multiple locations over a study area. I found that initial user parameterisation in a weather model had limited effect on pollution estimates from a dispersion model. I evaluated a new GIS-based dispersion model (5 x 5 m NO₂ estimates for a 3,500 km² area, with model run times of under 10 minutes). I demonstrated that inclusion of discrete street canyon models and geospatial surrogates (accounting for urban morphology) improved model accuracy. The measurement and modelling evaluation research in this thesis complimented each other by providing efficient ways to directly measure population exposures
Splice switching small molecules as inducers of apoptosis
Get PDFThis thesis was previously restricted to Strathclyde users only until 26th October 2023.One of the most important post-transcriptional processes that occurs during the transcription of DNA to RNA is alternative splicing. Alternative splicing is a highly regulated process that occurs during gene expression and is the basis for the large protein diversity that is achieved in eukaryotes. It allows multiple protein isoforms to be formed from one pre-mRNA sequence.;Although alternative splicing is necessary to provide protein diversity, aberrant splicing can also lead to diseases such as cancer. Recently, there has been an interest in the ability of small molecules to exogenously modulate alternative splicing as therapeutics for aberrant splicing diseases. The ellipticine analogue GQC-05 has been found to have splice switching capabilities towards the apoptotic oncogene Bcl-x, however the mode of action of GQC-05 is not understood.;This thesis describes efforts made to elucidate the mode of action of GQC-05 by synthesising a library of ellipticine derivatives for testing in a range of biochemical assays to evaluate their ability to bind and stabilise Bcl-x.;The background to alternative RNA splicing and the aberrant splicing process that can lead to diseases such as cancer is introduced in Chapter 1. The importance of the oncogene Bcl-x and the current limitations in targeting it therapeutically are also presented.;Chapter 2 investigates current literature methods to prepare 9-methoxyellipticine. However it is found that these methods do not provide a modular framework in which to systematically alter the ellipticine structure.;Chapter 3 describes the development of a one-pot, sequential, palladium cross-coupling methodology to construct the backbone of the natural product ellipticine. This methodology has been further extended to synthesise a range of ellipticine analogues with modular changes throughout the structure.;Chapter 4 examines the ability of the ellipticine derivatives synthesised to stabilise a putative Gquadruplex structure within Bcl-x through the use of UV melting assays. The ligands have also been investigated for their ability to stabilise a range of competitor DNA structures with the help of FRET melting assays. The interaction of GQC-05 with the putative Bcl-x G-quadruplex has also initially been examined using NMR spectroscopy. And finally, the ellipticine derivatives have been tested in Bcl-x in vitro splicing assays to determine whether they are capable of exerting the same splicing modulation on Bcl-x as their parent compound GQC-05.One of the most important post-transcriptional processes that occurs during the transcription of DNA to RNA is alternative splicing. Alternative splicing is a highly regulated process that occurs during gene expression and is the basis for the large protein diversity that is achieved in eukaryotes. It allows multiple protein isoforms to be formed from one pre-mRNA sequence.;Although alternative splicing is necessary to provide protein diversity, aberrant splicing can also lead to diseases such as cancer. Recently, there has been an interest in the ability of small molecules to exogenously modulate alternative splicing as therapeutics for aberrant splicing diseases. The ellipticine analogue GQC-05 has been found to have splice switching capabilities towards the apoptotic oncogene Bcl-x, however the mode of action of GQC-05 is not understood.;This thesis describes efforts made to elucidate the mode of action of GQC-05 by synthesising a library of ellipticine derivatives for testing in a range of biochemical assays to evaluate their ability to bind and stabilise Bcl-x.;The background to alternative RNA splicing and the aberrant splicing process that can lead to diseases such as cancer is introduced in Chapter 1. The importance of the oncogene Bcl-x and the current limitations in targeting it therapeutically are also presented.;Chapter 2 investigates current literature methods to prepare 9-methoxyellipticine. However it is found that these methods do not provide a modular framework in which to systematically alter the ellipticine structure.;Chapter 3 describes the development of a one-pot, sequential, palladium cross-coupling methodology to construct the backbone of the natural product ellipticine. This methodology has been further extended to synthesise a range of ellipticine analogues with modular changes throughout the structure.;Chapter 4 examines the ability of the ellipticine derivatives synthesised to stabilise a putative Gquadruplex structure within Bcl-x through the use of UV melting assays. The ligands have also been investigated for their ability to stabilise a range of competitor DNA structures with the help of FRET melting assays. The interaction of GQC-05 with the putative Bcl-x G-quadruplex has also initially been examined using NMR spectroscopy. And finally, the ellipticine derivatives have been tested in Bcl-x in vitro splicing assays to determine whether they are capable of exerting the same splicing modulation on Bcl-x as their parent compound GQC-05
Characterization of superelastic nitinol wire for application to aortic stent graft design
Get PDFAortic stent graft devices are required to treat patients with life-threatening vascular disease. These devices depend on superelastic Nitinol material for their ability to be delivered through a minimally invasive endovascular approach and then to self-expand for long-term implantation at the target site. In this safety-critical application, Nitinol stent components are subjected to challenging in-service conditions in terms of thermo-mechanical loading. Characterization of the material's response to these loading conditions is therefore essential for its safe and effective implementation in the design of medical devices. This thesis reports material characterization work performed on superelastic Nitinol stent wire under conditions relevant to its in-service application. The product life cycle of Nitinol stent graft components is investigated, highlighting the importance of the material's bending behaviour and the associated tensile and compressive mechanical responses. With tensile behaviour and test methods already well established for Nitinol, the work first focuses on developing a method for compressive testing of representative Nitinol wire material, building on a previous method to enable testing to higher strains. This allows characterization of the material in compression for thermo-mechanical loading representative of large compaction deformations, in-vivo cycling and different temperatures seen during production, sterilization and implantation. The results also allow a clear understanding of the material's tension-compression stress-strain asymmetry, which is essential to understanding its bending behaviour. This investigation concludes with a feasibility study into a novel compression test method developed by the author, using short wire samples with high-resolution 'microtester' equipment to obtain improved results. The work then focuses on development of a test method for bend testing of thin Nitinol wires to investigate the load response to in-service deformations at relevant test temperatures. This allows characterization of the wire's load-history dependent bending response, whereby the force exerted at a given deflection during unloading depends on the maximum deflection during loading, with interesting application possibilities for stent components. The testing also allows the material's temperature dependence, cyclic behaviour and large deformation response in bending to be studied. Following this, full-field strain measurement of thin Nitinol wires in bending is presented, achieved through application of 3-D microscopic Digital Image Correlation(DIC) technology. The development of a novel test method, together with extensive data analysis, provides results for characterization of the material's complex bending behaviour, allowing new insight to its tension-compression asymmetry, localised deformation, load-unload strain hysteresis and load-history dependence of strain state inbending. This testing provides useful quantitative characterisation data including neutral axis eccentricity at high bend deformations. Finally, Abaqus FEA software is used to investigate the effectiveness of its in-built superelastic constitutive model for representing the Nitinol stent wire's bending behaviour, and ultimately its suitability for use in stent design and analysis. The uniaxial stress-strain test results are used for input to the model, and then bending simulation results are compared against the experimental results, both in terms of force and strain outputs. Key findings include the model's inability to represent the strain localisation seen in bending experiments, leading to under-representation of the maximum strains for 'intermediate' bend deflections, and also the model's under-representation of unloading forces at these deflections (unless input parameters are adapted to compensate). Despite these limitations of the model, the cyclic stiffness and strain changes in bending are shown to be reasonably well represented, validating it for its primary use in fatigue analysis of stent components.Aortic stent graft devices are required to treat patients with life-threatening vascular disease. These devices depend on superelastic Nitinol material for their ability to be delivered through a minimally invasive endovascular approach and then to self-expand for long-term implantation at the target site. In this safety-critical application, Nitinol stent components are subjected to challenging in-service conditions in terms of thermo-mechanical loading. Characterization of the material's response to these loading conditions is therefore essential for its safe and effective implementation in the design of medical devices. This thesis reports material characterization work performed on superelastic Nitinol stent wire under conditions relevant to its in-service application. The product life cycle of Nitinol stent graft components is investigated, highlighting the importance of the material's bending behaviour and the associated tensile and compressive mechanical responses. With tensile behaviour and test methods already well established for Nitinol, the work first focuses on developing a method for compressive testing of representative Nitinol wire material, building on a previous method to enable testing to higher strains. This allows characterization of the material in compression for thermo-mechanical loading representative of large compaction deformations, in-vivo cycling and different temperatures seen during production, sterilization and implantation. The results also allow a clear understanding of the material's tension-compression stress-strain asymmetry, which is essential to understanding its bending behaviour. This investigation concludes with a feasibility study into a novel compression test method developed by the author, using short wire samples with high-resolution 'microtester' equipment to obtain improved results. The work then focuses on development of a test method for bend testing of thin Nitinol wires to investigate the load response to in-service deformations at relevant test temperatures. This allows characterization of the wire's load-history dependent bending response, whereby the force exerted at a given deflection during unloading depends on the maximum deflection during loading, with interesting application possibilities for stent components. The testing also allows the material's temperature dependence, cyclic behaviour and large deformation response in bending to be studied. Following this, full-field strain measurement of thin Nitinol wires in bending is presented, achieved through application of 3-D microscopic Digital Image Correlation(DIC) technology. The development of a novel test method, together with extensive data analysis, provides results for characterization of the material's complex bending behaviour, allowing new insight to its tension-compression asymmetry, localised deformation, load-unload strain hysteresis and load-history dependence of strain state inbending. This testing provides useful quantitative characterisation data including neutral axis eccentricity at high bend deformations. Finally, Abaqus FEA software is used to investigate the effectiveness of its in-built superelastic constitutive model for representing the Nitinol stent wire's bending behaviour, and ultimately its suitability for use in stent design and analysis. The uniaxial stress-strain test results are used for input to the model, and then bending simulation results are compared against the experimental results, both in terms of force and strain outputs. Key findings include the model's inability to represent the strain localisation seen in bending experiments, leading to under-representation of the maximum strains for 'intermediate' bend deflections, and also the model's under-representation of unloading forces at these deflections (unless input parameters are adapted to compensate). Despite these limitations of the model, the cyclic stiffness and strain changes in bending are shown to be reasonably well represented, validating it for its primary use in fatigue analysis of stent components
Development of a new diagnostic method for Human African Trypanosomiasis using Raman spectroscopy
Get PDFThis thesis was previously restricted to Strathclyde users only until 26th October 2023.Human African Trypanosomiasis (HAT) is a tsetse fly-transmitted parasitic disease found in Sub-Saharan Africa. Although responsible for deadly epidemics throughout the 20th century, a renewed commitment to disease control by the World Health Organisation and partners since 2000 has significantly reduced the number of new cases and motivated a target for the elimination of gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests, capable of detecting such cases are therefore needed.;This thesis investigates the potential of Raman spectroscopy as a diagnostic tool for HAT. Raman spectroscopy provides vibrational information about the composition of a matrix and could determine the biochemical changes that occurs during the infection, leading to the detection of diseased tissue. Lately, this technique has been extensively used for medical diagnostics and the recent technological advancements have improved the cost, sensitivity and portability of Raman technology, making Raman an attractive tool for the detection of HAT.;The aim of this thesis was to assess and develop a new diagnostic method for gambiense-HAT using Raman spectroscopy of the skin. Two sub-species of Trypanosoma brucei were analysed and biologically characterised, with the purpose of understanding the surface biological composition of the parasite and to obtain their Raman fingerprint. The skin of T. brucei-infected and uninfected mice was then investigated to measure spectral differences using statistical analysis, thus providing information on biochemical changes in infected skin.;This technique was then translated in situ by analysing infected mice over a time course of infection. Finally, this diagnostic method was tested in vivo on human patients in the field in collaboration with the HAT national control active screening program in Guinea. This study investigated for the first time, the application of Raman spectroscopy for the detection of gambiense-HAT by targeting the skin of the host. It has demonstrated significant potential to discriminate between infected and non-infected tissue and could represent a unique non-invasive diagnostic tool in the goal for elimination of T.b. gambiense disease.Human African Trypanosomiasis (HAT) is a tsetse fly-transmitted parasitic disease found in Sub-Saharan Africa. Although responsible for deadly epidemics throughout the 20th century, a renewed commitment to disease control by the World Health Organisation and partners since 2000 has significantly reduced the number of new cases and motivated a target for the elimination of gambiense-HAT by 2030. However, the recent identification of latent human infections, and the detection of trypanosomes in extravascular tissues hidden from current diagnostic tools, such as the skin, has added new complexity to identifying infected individuals. New and improved diagnostic tests, capable of detecting such cases are therefore needed.;This thesis investigates the potential of Raman spectroscopy as a diagnostic tool for HAT. Raman spectroscopy provides vibrational information about the composition of a matrix and could determine the biochemical changes that occurs during the infection, leading to the detection of diseased tissue. Lately, this technique has been extensively used for medical diagnostics and the recent technological advancements have improved the cost, sensitivity and portability of Raman technology, making Raman an attractive tool for the detection of HAT.;The aim of this thesis was to assess and develop a new diagnostic method for gambiense-HAT using Raman spectroscopy of the skin. Two sub-species of Trypanosoma brucei were analysed and biologically characterised, with the purpose of understanding the surface biological composition of the parasite and to obtain their Raman fingerprint. The skin of T. brucei-infected and uninfected mice was then investigated to measure spectral differences using statistical analysis, thus providing information on biochemical changes in infected skin.;This technique was then translated in situ by analysing infected mice over a time course of infection. Finally, this diagnostic method was tested in vivo on human patients in the field in collaboration with the HAT national control active screening program in Guinea. This study investigated for the first time, the application of Raman spectroscopy for the detection of gambiense-HAT by targeting the skin of the host. It has demonstrated significant potential to discriminate between infected and non-infected tissue and could represent a unique non-invasive diagnostic tool in the goal for elimination of T.b. gambiense disease
Single-shot holographic readout of an atom interferometer
No full textAtom interferometry is a precision measurement technique that encodes information in the phase of atomic wavefunctions, using matter-wave interference to project the encoded phase information onto some relatively easy-to-measure property at the interferometer output, like the fractional atomic population in a specific momentum or internal state. Atoms are perturbed by influences to which photons are insensitive, offering atom interferometers excellent sensitivity and access to physics outwith the range of conventional optical interferometers. As such, for probing of fundamental physics such as QED corrections, atoms are an obvious test bed. The primary focus of this thesis is the construction and development of an atom interferometer capable of performing single-shot measurements of the fine-structure constant using a holographic readout technique. This achievement allows the holographic interferometer an increased data acquisition rate on the order of 700-times that [sic] a conventional configuration. As an interfering medium we use a Bose-Einstein condensate containing around ~10[to the power of]5 87Rb atoms. We coherently manipulate the momentum of these atoms with the scattering of photons from an optical lattice with fully controllable intensity. We have developed a numerical toolbox capable of calculating optical-lattice pulse-sequences to generate arbitrary atom-optical operations such as mirrors, and beam-splitters, experimentally demonstrated with an efficiency of 99:97±0:03%. We have used these atom optics to create experimental atom interferometers with various applications, shown here in the cases of a magnetic gradiometer and in measurements of recoil frequency. This latter configuration has been used to perform a measurement of the fine-structure constant with a fractional uncertainty of 6500 ppm in a single shot, with a clear pathway to reduce this uncertainty to 2300 ppm per shot, whilst the increased speed of the holographic interferometer allows a corresponding reduction in uncertainty to 60 ppm within a twelve hour integration period.Atom interferometry is a precision measurement technique that encodes information in the phase of atomic wavefunctions, using matter-wave interference to project the encoded phase information onto some relatively easy-to-measure property at the interferometer output, like the fractional atomic population in a specific momentum or internal state. Atoms are perturbed by influences to which photons are insensitive, offering atom interferometers excellent sensitivity and access to physics outwith the range of conventional optical interferometers. As such, for probing of fundamental physics such as QED corrections, atoms are an obvious test bed. The primary focus of this thesis is the construction and development of an atom interferometer capable of performing single-shot measurements of the fine-structure constant using a holographic readout technique. This achievement allows the holographic interferometer an increased data acquisition rate on the order of 700-times that [sic] a conventional configuration. As an interfering medium we use a Bose-Einstein condensate containing around ~10[to the power of]5 87Rb atoms. We coherently manipulate the momentum of these atoms with the scattering of photons from an optical lattice with fully controllable intensity. We have developed a numerical toolbox capable of calculating optical-lattice pulse-sequences to generate arbitrary atom-optical operations such as mirrors, and beam-splitters, experimentally demonstrated with an efficiency of 99:97±0:03%. We have used these atom optics to create experimental atom interferometers with various applications, shown here in the cases of a magnetic gradiometer and in measurements of recoil frequency. This latter configuration has been used to perform a measurement of the fine-structure constant with a fractional uncertainty of 6500 ppm in a single shot, with a clear pathway to reduce this uncertainty to 2300 ppm per shot, whilst the increased speed of the holographic interferometer allows a corresponding reduction in uncertainty to 60 ppm within a twelve hour integration period
The influence of social eWOM information on attitude formation for aesthetic products : the case of fine art
Get PDFThis research aims to further our understanding about the influence of eWOM communication on consumers' decision-making process and its effects on the development of aesthetic product attitudes in an online social context. The growing number of studies that explore the influence of online WOM information on consumer decision-making still presents a lack of understanding in specific consumption contexts.;This requires further theoretical development on the modality in which eWOM communication retrieved from social platforms alters the decision-processes in emotionally rich consumption contexts. Accordingly, given aesthetic product typology's recent market trends, and art in particular, which saw a shift from predominantly offline consumption towards online mediated channels, fine art has been chosen as the subject of the current study as the prototypical example of an aesthetic good.;A mixed-method approach within a pragmatic philosophical stance was deemed most suitable to explore the research problem. The lack of research within the area called for an initial qualitative method of data collection in the form of in-depth interviews. A total of 28 in-depth interviews were carried out with different groups of stakeholders, such as commercial galleries, consumers, artists etc. This phase of the study helped pare down the number of variables to be included in the model and offered an indication of the experimental design requirements.;The primary phrase of research consisted of a quantitative data collection in the form of an online administrated experiment. This stage sought to test the developed product attitude formation model, accounting for the influence of social eWOM information. A total of 426 responses were collected, and data were subjected to statistical analyses, specifically analyses of variance and SEM.;The findings of this research highlight several contributions to theory, which advances our understanding of how consumers form product attitudes in an online social context, particularly attitudes towards aesthetic products.;Firstly, this study found that the attitude a consumer develops about an aesthetic product in an information-rich context is not pre-determined by the product typology, but depends on consumer-specific factors. In this instance, eWOM information enters the process as cognitive input and induces a shift in product preferences that suppress the influence of affect that was previously considered of paramount importance.;Secondly, the study highlights the importance of the purchase motivations of the consumer as, these act upon the extent of influence that eWOM information has on product attitude. Thirdly, the study identified the specific dimensions of eWOM that exhibit a differential impact upon product attitude development. Fourthly, a new theoretical model that accounts for the aesthetic product attitude formation process was developed and defined by the variables that exert an influence on the process in an online social context.;The results of this study provide several managerial recommendations that help inform marketing practice, given the pervasive adoption of social media for following and purchasing aesthetic products.This research aims to further our understanding about the influence of eWOM communication on consumers' decision-making process and its effects on the development of aesthetic product attitudes in an online social context. The growing number of studies that explore the influence of online WOM information on consumer decision-making still presents a lack of understanding in specific consumption contexts.;This requires further theoretical development on the modality in which eWOM communication retrieved from social platforms alters the decision-processes in emotionally rich consumption contexts. Accordingly, given aesthetic product typology's recent market trends, and art in particular, which saw a shift from predominantly offline consumption towards online mediated channels, fine art has been chosen as the subject of the current study as the prototypical example of an aesthetic good.;A mixed-method approach within a pragmatic philosophical stance was deemed most suitable to explore the research problem. The lack of research within the area called for an initial qualitative method of data collection in the form of in-depth interviews. A total of 28 in-depth interviews were carried out with different groups of stakeholders, such as commercial galleries, consumers, artists etc. This phase of the study helped pare down the number of variables to be included in the model and offered an indication of the experimental design requirements.;The primary phrase of research consisted of a quantitative data collection in the form of an online administrated experiment. This stage sought to test the developed product attitude formation model, accounting for the influence of social eWOM information. A total of 426 responses were collected, and data were subjected to statistical analyses, specifically analyses of variance and SEM.;The findings of this research highlight several contributions to theory, which advances our understanding of how consumers form product attitudes in an online social context, particularly attitudes towards aesthetic products.;Firstly, this study found that the attitude a consumer develops about an aesthetic product in an information-rich context is not pre-determined by the product typology, but depends on consumer-specific factors. In this instance, eWOM information enters the process as cognitive input and induces a shift in product preferences that suppress the influence of affect that was previously considered of paramount importance.;Secondly, the study highlights the importance of the purchase motivations of the consumer as, these act upon the extent of influence that eWOM information has on product attitude. Thirdly, the study identified the specific dimensions of eWOM that exhibit a differential impact upon product attitude development. Fourthly, a new theoretical model that accounts for the aesthetic product attitude formation process was developed and defined by the variables that exert an influence on the process in an online social context.;The results of this study provide several managerial recommendations that help inform marketing practice, given the pervasive adoption of social media for following and purchasing aesthetic products
Towards displacing domestic air conditioning in KSA : an assessment of hybrid cooling strategies integrated with 'Fabric First' passive design measures
Get PDFReducing energy use and CO2 emissions to curb global warming and climate change are the greatest challenges now facing mankind. The vast majority of energy generated from fossil fuels is burned to run vehicles, fuel power stations and cool or heat homes. Saudi Arabia, the world's largest producer and exporter of petroleum, currently consumes almost three times higher than the world average energy use and hence; ranked ninth among nations for CO2 emissions. Among all fossil energy consumers, residential buildings use almost half of the Saudi's prime energy sources and are responsible for almost 50% of the emitted CO2. In such a hot climate region, air conditioning (AC) of dwellings is by far the major consumer representing 69% of domestic energy use and drives peak loading. Future projections predict a continuous increase in energy use as the majority of existing buildings are poorly designed for the prevailing climate, leading to excessive use of mechanical AC. Therefore, it is crucial for Saudi Arabia to consider a horizon where hydrocarbons are not the dominant energy resource. The adoption of energy efficiency measures and low carbon cooling strategies may have the potential to displace a substantial percentage of oil currently used to run conventional AC plants. Therefore, the current study investigates the viability of 'fabric first' intelligent architectural design measures, in combination with hybrid ground cooling pipes integrated with black-body radiant night cooling systems, with a specific purpose to displace AC systems and decrease the carbon footprint while sustaining year-round thermal comfort. The interrogation of this hypothesis was addressed in three stages. The first stage was to generate a baseline analysis of the thermo-physical and energy performance of a typical residential block in Jeddah. The second stage involved developing an alternative low energy cooling approach that could handle high ambient temperatures. The task involved designing ground pipe ventilation integrated with high emissivity blackbody radiator to displace AC systems. The design of such 'hybrid' system required a parametric analysis combined with testing prototypes in field trials to establish actual ground temperatures at various depths and black body emissivity ranges under different sky conditions. This hybrid system became the subject of numerical modelling and simulation using DesignBuilder software in conjunction with EnergyPlus simulation engine. The third stage was to assess the simulation results and validate the cooling efficiency and cost-effectiveness of the hybrid system compared to the baseline. The preliminary results of prototype thermal simulation and field trials suggest that 'fabric first' passive designs and measures (PDMs), combined with night hydronic radiant cooling (HRCS) and supply ventilation via ground pipes (GPCS), can negate the necessity for a standard AC system by displacing over 80% of cooling demand and lower the carbon footprint of a typical housing block by over 75%. Such passive and hybrid system applications also have a remarkably short payback period with energy savings offsetting the capital costs associated with building thermo-physical enhancement.Reducing energy use and CO2 emissions to curb global warming and climate change are the greatest challenges now facing mankind. The vast majority of energy generated from fossil fuels is burned to run vehicles, fuel power stations and cool or heat homes. Saudi Arabia, the world's largest producer and exporter of petroleum, currently consumes almost three times higher than the world average energy use and hence; ranked ninth among nations for CO2 emissions. Among all fossil energy consumers, residential buildings use almost half of the Saudi's prime energy sources and are responsible for almost 50% of the emitted CO2. In such a hot climate region, air conditioning (AC) of dwellings is by far the major consumer representing 69% of domestic energy use and drives peak loading. Future projections predict a continuous increase in energy use as the majority of existing buildings are poorly designed for the prevailing climate, leading to excessive use of mechanical AC. Therefore, it is crucial for Saudi Arabia to consider a horizon where hydrocarbons are not the dominant energy resource. The adoption of energy efficiency measures and low carbon cooling strategies may have the potential to displace a substantial percentage of oil currently used to run conventional AC plants. Therefore, the current study investigates the viability of 'fabric first' intelligent architectural design measures, in combination with hybrid ground cooling pipes integrated with black-body radiant night cooling systems, with a specific purpose to displace AC systems and decrease the carbon footprint while sustaining year-round thermal comfort. The interrogation of this hypothesis was addressed in three stages. The first stage was to generate a baseline analysis of the thermo-physical and energy performance of a typical residential block in Jeddah. The second stage involved developing an alternative low energy cooling approach that could handle high ambient temperatures. The task involved designing ground pipe ventilation integrated with high emissivity blackbody radiator to displace AC systems. The design of such 'hybrid' system required a parametric analysis combined with testing prototypes in field trials to establish actual ground temperatures at various depths and black body emissivity ranges under different sky conditions. This hybrid system became the subject of numerical modelling and simulation using DesignBuilder software in conjunction with EnergyPlus simulation engine. The third stage was to assess the simulation results and validate the cooling efficiency and cost-effectiveness of the hybrid system compared to the baseline. The preliminary results of prototype thermal simulation and field trials suggest that 'fabric first' passive designs and measures (PDMs), combined with night hydronic radiant cooling (HRCS) and supply ventilation via ground pipes (GPCS), can negate the necessity for a standard AC system by displacing over 80% of cooling demand and lower the carbon footprint of a typical housing block by over 75%. Such passive and hybrid system applications also have a remarkably short payback period with energy savings offsetting the capital costs associated with building thermo-physical enhancement
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