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Development of novel methods for extended exposure assessment of combustion-related air pollutants in indoor and outdoor locations
Get PDFBackground & Aims: There is on-going and growing concern regarding acute and chronic human health effects associated with exposure to combustion-related air pollutants. This thesis describes the development and evaluation of novel methods for assessing exposure to combustion-related air pollutants [particulate matter (PM),black carbon (BC) and nitrogen dioxide (NO₂)] in indoor and outdoor environments.Methods: The methods that were developed and evaluated included: mass and darkness/colour analysis of airborne particle samples; passive samplers; portable real time monitors; and GC-MS analysis of particulate-bound polycyclic aromatic hydrocarbons (pPAHs). These methods were used to measure PM, BC and NO₂ in indoor offices and outdoor streets in Glasgow city centre, and an industrial hydraulic fracturing test site in Poland.Results: Detailed evaluation and calibration of novel methods for darkness measurement of low mass particulate material specimens collected on filters were completed to allow subsequent application in BC exposure estimation. Similarly,detailed evaluation allowed the refinement of procedures for field calibration of portable real-time monitors for BC, NO₂ and O₃. Indoor concentrations of PM, BC and NO₂ measured using the calibrated monitoring instruments were influenced by outdoor sources through natural ventilation and the proximity of buildings to urban roadsides. Outdoor measurements at 2 heights indicated that children are likely to experience higher exposures to combustion-related air pollutants from vehicle emissions. Marked elevations of BC and NO₂ concentrations were observed in downwind proximity to industrial fracking equipment sources, where average BC and NO₂ concentrations (11.2 & 111.3 μg/m³) were 2 to 3 times higher than average BC and NO₂ exposures experienced while walking in Glasgow city centre (3.7 & 42.3 μg/m³).Conclusions: Novel exposure science and environmental engineering approaches were developed to allow improved characterisation of short-term to medium-term personal and environmental exposures to combustion-related air pollutants in a wide range of occupational and environmental settings.Keywords: Combustion-related air pollutants; PM; BC; NO₂, novel methods.Background & Aims: There is on-going and growing concern regarding acute and chronic human health effects associated with exposure to combustion-related air pollutants. This thesis describes the development and evaluation of novel methods for assessing exposure to combustion-related air pollutants [particulate matter (PM),black carbon (BC) and nitrogen dioxide (NO₂)] in indoor and outdoor environments.Methods: The methods that were developed and evaluated included: mass and darkness/colour analysis of airborne particle samples; passive samplers; portable real time monitors; and GC-MS analysis of particulate-bound polycyclic aromatic hydrocarbons (pPAHs). These methods were used to measure PM, BC and NO₂ in indoor offices and outdoor streets in Glasgow city centre, and an industrial hydraulic fracturing test site in Poland.Results: Detailed evaluation and calibration of novel methods for darkness measurement of low mass particulate material specimens collected on filters were completed to allow subsequent application in BC exposure estimation. Similarly,detailed evaluation allowed the refinement of procedures for field calibration of portable real-time monitors for BC, NO₂ and O₃. Indoor concentrations of PM, BC and NO₂ measured using the calibrated monitoring instruments were influenced by outdoor sources through natural ventilation and the proximity of buildings to urban roadsides. Outdoor measurements at 2 heights indicated that children are likely to experience higher exposures to combustion-related air pollutants from vehicle emissions. Marked elevations of BC and NO₂ concentrations were observed in downwind proximity to industrial fracking equipment sources, where average BC and NO₂ concentrations (11.2 & 111.3 μg/m³) were 2 to 3 times higher than average BC and NO₂ exposures experienced while walking in Glasgow city centre (3.7 & 42.3 μg/m³).Conclusions: Novel exposure science and environmental engineering approaches were developed to allow improved characterisation of short-term to medium-term personal and environmental exposures to combustion-related air pollutants in a wide range of occupational and environmental settings.Keywords: Combustion-related air pollutants; PM; BC; NO₂, novel methods
Theoretical modelling of the collapse of a shelled ultrasound contrast agent used in the treatment of cancer
Get PDFStrathclyde theses - ask staff. Thesis no. : T14627Premanufactured shelled microbubbles composed of a protein shell are currently licensed in the UK as ultrasound imaging contrast agents. Current research is focussing on using the shelled microbubbles as transportation mechanisms for localised drug delivery particularly in the treatment of various types of cancer. The aim of this PhD study is to identify how the shell's material parameters influence the collapse and relaxation times of the shelled microbubbles. A theoretical model is proposed which utilises an analytical approach to predict the dynamics of a stressed, compressible shelled microbubble. This model can be used to identify the optimal material parameters for the shells. A neo-Hookean, compressible strain energy density function is used to model the potential energy per unit volume of the shell. A stress is applied to the inner surface of the spherical shell whilst setting the outer surface's stress to zero. The collapse phase of the stressed shelled microbubble is then considered. Applying the momentum balance law,a dynamical model is used to predict the dynamics of the collapsing shelled microbubble. An analytical approach is adopted using an asymptotic expansion. A second model is then constructed to model the deformation of an open, shelled microbubble. This is achieved by considering a reference configuration (stress free)consisting of a shelled microbubble with a spherical cap removed. This is then deformed angularly and radially by applying a stress load to the free edge of the shell. This forms a deformed open sphere possessing a stress. This is used to represent the change in geometry of a shelled microbubble. The third and final model focusses on developing a Rayleigh-Plesset equation for an incompressible,thin shelled, gas loaded shelled microbubble with a shell that is composed of a liquid-crystalline material. The technique of linearisation is used to predict the shelled microbubble's natural frequency and relaxation time. The influence of the material properties of the shell on the natural frequency and relaxation time are discussed.Premanufactured shelled microbubbles composed of a protein shell are currently licensed in the UK as ultrasound imaging contrast agents. Current research is focussing on using the shelled microbubbles as transportation mechanisms for localised drug delivery particularly in the treatment of various types of cancer. The aim of this PhD study is to identify how the shell's material parameters influence the collapse and relaxation times of the shelled microbubbles. A theoretical model is proposed which utilises an analytical approach to predict the dynamics of a stressed, compressible shelled microbubble. This model can be used to identify the optimal material parameters for the shells. A neo-Hookean, compressible strain energy density function is used to model the potential energy per unit volume of the shell. A stress is applied to the inner surface of the spherical shell whilst setting the outer surface's stress to zero. The collapse phase of the stressed shelled microbubble is then considered. Applying the momentum balance law,a dynamical model is used to predict the dynamics of the collapsing shelled microbubble. An analytical approach is adopted using an asymptotic expansion. A second model is then constructed to model the deformation of an open, shelled microbubble. This is achieved by considering a reference configuration (stress free)consisting of a shelled microbubble with a spherical cap removed. This is then deformed angularly and radially by applying a stress load to the free edge of the shell. This forms a deformed open sphere possessing a stress. This is used to represent the change in geometry of a shelled microbubble. The third and final model focusses on developing a Rayleigh-Plesset equation for an incompressible,thin shelled, gas loaded shelled microbubble with a shell that is composed of a liquid-crystalline material. The technique of linearisation is used to predict the shelled microbubble's natural frequency and relaxation time. The influence of the material properties of the shell on the natural frequency and relaxation time are discussed
Pharmacological characterisation of the 5-HT receptors present on mouse and human hepatic stellate cells and their role in liver fibrosis
Get PDFThis thesis was previously held under moratorium in the Chemistry department (GSK) from 31st May 2017 until 31st May 2019.The prevalence of chronic liver disease is rising worldwide with a clear unmet need for therapy: The only current treatment is liver transplant or elimination of the underlying cause. The hepatic stellate cell (HSC) has been identified as the fibrogenic cell type responsible for scarring. Following liver injury HSCs are activated, transforming into a proliferating, perpetuating population of myofibroblast–like cells, that secrete extracellular matrix. Evidence that serotonin (5-HT) influences HSC biology has been reported, with activation up-regulating the expression of 5-HT2A, 5-HT2B and 5HT1B receptors and therefore have potential as targets for therapy. In this thesis an 'in-depth' quantitative pharmacological characterisation of the 5-HT receptors present on mouse and human HSCs was undertaken to fully evaluate and extend the evidence for a role of 5-HT in driving the fibrogenic process. The 5-HT2A receptor was demonstrated pharmacologically to be responsible for both 5-HT-stimulated intracellular calcium signalling in mouse and human HSCs and for extracellular regulated kinase (ERK) phosphorylation signal in mouse HSCs. A second 5-HT receptor responsible for ERK phosphorylation was found to be present on mouse HSCs, with pharmacological properties suggesting the 5-HT1B receptor as the most likely candidate. The role of 5-HT in fibrotic phenotypic endpoints of proliferation and collagen production was also investigated with no evidence of a role for 5-HT identified. Although 5-HT was reported to enhance platelet derived growth factor (PDGF)-induced proliferation, 5-HT was found only to enhance the PDGF-induced ERK phosphorylation in mouse HSCs. These data, therefore, did not support a role for 5-HT in driving HSCs fibrogenesis in a mouse CCl4 liver injury model the consistent delivery of low pharmacologically selective doses of a selective 5-HT2A and 5-HT2B antagonist, volinanserin and GSK1606260A respectively, were evaluated. Volinanserin was found to have no anti-fibrotic effect whereas GSK1606260A was pro-fibrotic. These data highlights the challenge of reliance on in vitro single cell type assays and their translation into in vivo models. Taken together these data were not consistent with the functional 5-HT2A and 5-HT1B receptors present on HSCs playing a key role in driving fibrosis and suggest they do not present a viable anti-fibrotic therapy opportunity.The prevalence of chronic liver disease is rising worldwide with a clear unmet need for therapy: The only current treatment is liver transplant or elimination of the underlying cause. The hepatic stellate cell (HSC) has been identified as the fibrogenic cell type responsible for scarring. Following liver injury HSCs are activated, transforming into a proliferating, perpetuating population of myofibroblast–like cells, that secrete extracellular matrix. Evidence that serotonin (5-HT) influences HSC biology has been reported, with activation up-regulating the expression of 5-HT2A, 5-HT2B and 5HT1B receptors and therefore have potential as targets for therapy. In this thesis an 'in-depth' quantitative pharmacological characterisation of the 5-HT receptors present on mouse and human HSCs was undertaken to fully evaluate and extend the evidence for a role of 5-HT in driving the fibrogenic process. The 5-HT2A receptor was demonstrated pharmacologically to be responsible for both 5-HT-stimulated intracellular calcium signalling in mouse and human HSCs and for extracellular regulated kinase (ERK) phosphorylation signal in mouse HSCs. A second 5-HT receptor responsible for ERK phosphorylation was found to be present on mouse HSCs, with pharmacological properties suggesting the 5-HT1B receptor as the most likely candidate. The role of 5-HT in fibrotic phenotypic endpoints of proliferation and collagen production was also investigated with no evidence of a role for 5-HT identified. Although 5-HT was reported to enhance platelet derived growth factor (PDGF)-induced proliferation, 5-HT was found only to enhance the PDGF-induced ERK phosphorylation in mouse HSCs. These data, therefore, did not support a role for 5-HT in driving HSCs fibrogenesis in a mouse CCl4 liver injury model the consistent delivery of low pharmacologically selective doses of a selective 5-HT2A and 5-HT2B antagonist, volinanserin and GSK1606260A respectively, were evaluated. Volinanserin was found to have no anti-fibrotic effect whereas GSK1606260A was pro-fibrotic. These data highlights the challenge of reliance on in vitro single cell type assays and their translation into in vivo models. Taken together these data were not consistent with the functional 5-HT2A and 5-HT1B receptors present on HSCs playing a key role in driving fibrosis and suggest they do not present a viable anti-fibrotic therapy opportunity
Modelling and analysis of energy demand variation and uncertainty in small-scale domestic energy systems
Get PDFA range of different scenarios have been predicted for future UK energy supply. While there is significant uncertainty, all expect an increase in small-scale distributed generation integrated in constrained or independent networks and with predominantly domestic consumers. This reduction in system scale has not, however, driven a significant change in design practices, with deterministic models and rules-of-thumb prevalent. Little consideration has been given to how the specific household characteristics and the size of system impact on demand level and timing, the degree of uncertainty in anydemand prediction, and how design practices should change to reflect this. The main contribution of the presented work has been to address this. To allow the variation and uncertainty to be quantified; a highly differentiated, probabilistic, bottom-up demand model has been developed for electrical and hot water use. The 1-minute resolution model incorporates an enhanced Markov chain occupancy model and is based on a newly developed discrete-event approach for occupant-initiated demands. Utilising realistic factoring for appliance ownership, income, occupancy, and random energy-use behaviours, the model has been shown to capture the range of potential household demands. Assessment that the developed model, and any existing model calibrated using group data, tended to rapidly converge to the group average basis, prompted further method development to improve the model's performance in capturing individual household demand behaviours. Analysis of both existing data and the demand model output has shown that energy system demand can vary significantly based on socio-economic characteristics and the types of households supplied. It also highlights that demand uncertainty for individual households can exceed an order of magnitude, even if household characteristics are known. As the system scale is increased, the level of overall demand uncertainty remains significant to at least 200 household systems. A method has therefore been developed that allows multiple runs of the probabilistic model to be reduced to a representative subset, which can be used to analyse potential energy system performance scenarios probabilistically using existing optimisation tools.A range of different scenarios have been predicted for future UK energy supply. While there is significant uncertainty, all expect an increase in small-scale distributed generation integrated in constrained or independent networks and with predominantly domestic consumers. This reduction in system scale has not, however, driven a significant change in design practices, with deterministic models and rules-of-thumb prevalent. Little consideration has been given to how the specific household characteristics and the size of system impact on demand level and timing, the degree of uncertainty in anydemand prediction, and how design practices should change to reflect this. The main contribution of the presented work has been to address this. To allow the variation and uncertainty to be quantified; a highly differentiated, probabilistic, bottom-up demand model has been developed for electrical and hot water use. The 1-minute resolution model incorporates an enhanced Markov chain occupancy model and is based on a newly developed discrete-event approach for occupant-initiated demands. Utilising realistic factoring for appliance ownership, income, occupancy, and random energy-use behaviours, the model has been shown to capture the range of potential household demands. Assessment that the developed model, and any existing model calibrated using group data, tended to rapidly converge to the group average basis, prompted further method development to improve the model's performance in capturing individual household demand behaviours. Analysis of both existing data and the demand model output has shown that energy system demand can vary significantly based on socio-economic characteristics and the types of households supplied. It also highlights that demand uncertainty for individual households can exceed an order of magnitude, even if household characteristics are known. As the system scale is increased, the level of overall demand uncertainty remains significant to at least 200 household systems. A method has therefore been developed that allows multiple runs of the probabilistic model to be reduced to a representative subset, which can be used to analyse potential energy system performance scenarios probabilistically using existing optimisation tools
Modelling of tides, waves and currents in coastal waters : hydrodynamics of the Firth of Clyde and of the east coast of Scotland
Get PDFThe thesis here presented is based on three main parts. The first part of the thes is based on modelling the water circulation of the Clyde Sea, in order to understand the dynamics of the dispersion of the Neprophs larvae. Previous researches in this area of Scotland highlighted the importance of the temperature- and saline-driven circulation in the Clyde Sea. However, few researches were focused on the surge dynamics, that are governing the dynamics of the water level in winter.;A three-dimensional finite-volume model was used to simulate the surge propagation, while a historical re-analysis was applied to understand the pattern and the propagation of the surge wave in the Clyde.The results highlighted that the largest storms that hit the Clyde in the past 30 years were mostly generated in the North Atlantic. Most interestingly, the results also suggest that severe surges are not only caused by extreme surge events, but also by the coupling of spring high tides with moderate surges.;In the second part the coupled dynamics of waves, tides and wind-driven circulation in the east coast of Scotland are studied. Wave-Current Interactions (WCI) are particularly relevant close to the coastline, where the effect of the spectral dispersion and wave breaking are more important and where the currents are stronger. The results showed that the coupling of strong currents with large waves travelling inopposite direction could enhance in east coast of Scotland the significant wave height (Hs) up to 3 m, threatening potentially infrastructures and ships near the coastline.;The last part of the thesis was dedicated to an experimental study of rogue waves in crossing sea. Crossing sea is one of the most common state in world seas, and occurs when a wind-generated wave train interact with another train of waves, that can be swell waves or another wind-generated wave train, maybe caused by a rapidly turning wind direction. Some numerical studies showed that this interaction can lead to the mechanism of modulation instability and, consequently, to the formation of rogue waves. A water tank experiment was carried out to confirm this theory.;The results shows that the angle of the interaction is a fundamental variable that can decrease or increase the instability of the wave train. However, most interestingly, in the sameconditions, the monochromatic sea state was showing a larger number of rogue waves than the crossing sea.The thesis here presented is based on three main parts. The first part of the thes is based on modelling the water circulation of the Clyde Sea, in order to understand the dynamics of the dispersion of the Neprophs larvae. Previous researches in this area of Scotland highlighted the importance of the temperature- and saline-driven circulation in the Clyde Sea. However, few researches were focused on the surge dynamics, that are governing the dynamics of the water level in winter.;A three-dimensional finite-volume model was used to simulate the surge propagation, while a historical re-analysis was applied to understand the pattern and the propagation of the surge wave in the Clyde.The results highlighted that the largest storms that hit the Clyde in the past 30 years were mostly generated in the North Atlantic. Most interestingly, the results also suggest that severe surges are not only caused by extreme surge events, but also by the coupling of spring high tides with moderate surges.;In the second part the coupled dynamics of waves, tides and wind-driven circulation in the east coast of Scotland are studied. Wave-Current Interactions (WCI) are particularly relevant close to the coastline, where the effect of the spectral dispersion and wave breaking are more important and where the currents are stronger. The results showed that the coupling of strong currents with large waves travelling inopposite direction could enhance in east coast of Scotland the significant wave height (Hs) up to 3 m, threatening potentially infrastructures and ships near the coastline.;The last part of the thesis was dedicated to an experimental study of rogue waves in crossing sea. Crossing sea is one of the most common state in world seas, and occurs when a wind-generated wave train interact with another train of waves, that can be swell waves or another wind-generated wave train, maybe caused by a rapidly turning wind direction. Some numerical studies showed that this interaction can lead to the mechanism of modulation instability and, consequently, to the formation of rogue waves. A water tank experiment was carried out to confirm this theory.;The results shows that the angle of the interaction is a fundamental variable that can decrease or increase the instability of the wave train. However, most interestingly, in the sameconditions, the monochromatic sea state was showing a larger number of rogue waves than the crossing sea
Novel methods for monitoring grout penetration in hard rock
Get PDFGrouting has been used in ground engineering since the early 19th century. Grouts are injected into the ground both for the creation of hydraulic barriers and for ensuring ground stability. Example applications are dam sealing, underground isolation of waste disposal sites, stabilisation of mine workings and prevention of water ingress during tunnelling. A key problem facing the grouting industry is that once the grout has been injected into the ground, it is impossible to detect where the grout material has gone. As a consequence, the integrity of the hydraulic barrier, or in the case of ground improvement the filling of all significant voids, cannot be guaranteed. This leads to huge conservatism in the industry, with large numbers of unnecessary injection boreholes being drilled. This Ph.D. thesis aims to create a detectable grout by the addition of magnetic materials to traditional cementitious grouts. Laboratory experiments have been undertaken to determine both the magnetic susceptibility and engineering properties of the detectable grout. These experiments have shown that, with the addition of magnetite, a viable detectable cementitious grout mixture can be produced. Samples of the detectable grout were then produced for use in two field trials. The first field trial provided the proof of concept that the grout could be detected both outside of the laboratory environment and at depth. The second field trial established how the magnetic field of the detectable grout changed with distance. The rate of decay of the magnetic field in all directions was established, with the grout being detected at a maximum distance of 3 m. This thesis has provided the first proof of concept that a magnetically susceptible cementitious grout, once injected into the subsurface, can be detected with a magnetometer. The data could then be used to determine the location and shape of the grouted rock volume. This detectable grouting system has the potential to reduce the inefficiencies and uncertainties currently present in the grouting industry.Grouting has been used in ground engineering since the early 19th century. Grouts are injected into the ground both for the creation of hydraulic barriers and for ensuring ground stability. Example applications are dam sealing, underground isolation of waste disposal sites, stabilisation of mine workings and prevention of water ingress during tunnelling. A key problem facing the grouting industry is that once the grout has been injected into the ground, it is impossible to detect where the grout material has gone. As a consequence, the integrity of the hydraulic barrier, or in the case of ground improvement the filling of all significant voids, cannot be guaranteed. This leads to huge conservatism in the industry, with large numbers of unnecessary injection boreholes being drilled. This Ph.D. thesis aims to create a detectable grout by the addition of magnetic materials to traditional cementitious grouts. Laboratory experiments have been undertaken to determine both the magnetic susceptibility and engineering properties of the detectable grout. These experiments have shown that, with the addition of magnetite, a viable detectable cementitious grout mixture can be produced. Samples of the detectable grout were then produced for use in two field trials. The first field trial provided the proof of concept that the grout could be detected both outside of the laboratory environment and at depth. The second field trial established how the magnetic field of the detectable grout changed with distance. The rate of decay of the magnetic field in all directions was established, with the grout being detected at a maximum distance of 3 m. This thesis has provided the first proof of concept that a magnetically susceptible cementitious grout, once injected into the subsurface, can be detected with a magnetometer. The data could then be used to determine the location and shape of the grouted rock volume. This detectable grouting system has the potential to reduce the inefficiencies and uncertainties currently present in the grouting industry
Pirates, merchants, and imperial authority in the British Atlantic, 1716-1726
Get PDFThis thesis was previously held under moratorium from 25th April 2018 until 1st May 2023Between 1716 and 1726, there was a surge in piracy in the Caribbean Sea, NorthAmerica, Africa, and the Indian Ocean. British state, colonial, and local responses toincreased reports of piracy differed across these colonial and geographical divides.British mercantile groups with stakes in the Caribbean sugar, Virginian tobacco, andAfrican slave trade lobbied when these markets were impacted by piracy. Likewise, theEast India Company exerted extensive influence when piratical operations spread to theIndian Ocean. The British state, moved by these groups, responded with multipleinitiatives to stem the impact of piracy on important commercial areas. At the sametime, colonial agents both supplied pirates and subsidised local campaigns against piracy.This project explores the multifaceted nature of the suppression of piracy withincolonial and metropolitan contexts to explain that multiple participants operating indistant but connected theatres influenced and shaped anti-piracy campaigns. Such anexamination challenges current understanding of the war against piracy, while providingnovel insight into imperial authority, state-empire relations, and the multilateral Atlanticeconomy. In this way, both pirate ships and the ships that hunted them are the lensthrough which to observe and understand the British Atlantic world in the earlyeighteenth century.Between 1716 and 1726, there was a surge in piracy in the Caribbean Sea, NorthAmerica, Africa, and the Indian Ocean. British state, colonial, and local responses toincreased reports of piracy differed across these colonial and geographical divides.British mercantile groups with stakes in the Caribbean sugar, Virginian tobacco, andAfrican slave trade lobbied when these markets were impacted by piracy. Likewise, theEast India Company exerted extensive influence when piratical operations spread to theIndian Ocean. The British state, moved by these groups, responded with multipleinitiatives to stem the impact of piracy on important commercial areas. At the sametime, colonial agents both supplied pirates and subsidised local campaigns against piracy.This project explores the multifaceted nature of the suppression of piracy withincolonial and metropolitan contexts to explain that multiple participants operating indistant but connected theatres influenced and shaped anti-piracy campaigns. Such anexamination challenges current understanding of the war against piracy, while providingnovel insight into imperial authority, state-empire relations, and the multilateral Atlanticeconomy. In this way, both pirate ships and the ships that hunted them are the lensthrough which to observe and understand the British Atlantic world in the earlyeighteenth century
The influence of intermittent hypoxia training on motor performance in healthy subjects
No full textSpinal cord injury (SCI) disrupts the communication between the brain and the spinal cord. Rehabilitation methods have focused on promoting activity-dependent plasticity through high intensity, high repetition training programmes. There is a marked increase of elderly patients with SCI because of an increase in life expectancy. This form of rehabilitation is problematic and researchers are investigating novel treatment methods. Neural plasticity has been observed following intermittent hypoxia (IH) in respiratory and non-respiratory neurons. Only a single treatment showed a significant improvement in lower limb function. The study investigated if the conduction and excitability within ascending spinal tracts are influenced by IH. To assess this an electrical stimulus was delivered at the median or tibial nerve for 4 minutes. Three recordings were taken before, during and following the treatment. This creates somatosensory evoked potentials (SEPs) that were recorded using scalp electrodes. Nine healthy adults (21-35 yrs.) were exposed to the IH treatment which involves one-minute sessions of repeated exposures of hypoxic (FIo2= 0.09) and normoxic (FIo2= 0.21) air for 30 minutes. The oxygen saturation level (SpO2) did not drop below 96.6%. This indicated that for the subjects tested the IH treatment failed to produce the marked reduction in the O2 saturation that was observed in spinal cord injured patients. This explains why there was no significant difference in the peak to peak amplitude of the SEPs when comparing the values before with during and after IH (p>0.05; two-tailed paired t-test). Furthermore, the heart rate and blood pressure were monitored and since the SpO2 level did not drop as low as 81% there was no significant change in blood pressure and heart rate following the treatment (p>0.05; two-tailed paired t-test). Under the circumstances that the protocol was not effective we can conclude that it provides a way of creating a sham condition.Spinal cord injury (SCI) disrupts the communication between the brain and the spinal cord. Rehabilitation methods have focused on promoting activity-dependent plasticity through high intensity, high repetition training programmes. There is a marked increase of elderly patients with SCI because of an increase in life expectancy. This form of rehabilitation is problematic and researchers are investigating novel treatment methods. Neural plasticity has been observed following intermittent hypoxia (IH) in respiratory and non-respiratory neurons. Only a single treatment showed a significant improvement in lower limb function. The study investigated if the conduction and excitability within ascending spinal tracts are influenced by IH. To assess this an electrical stimulus was delivered at the median or tibial nerve for 4 minutes. Three recordings were taken before, during and following the treatment. This creates somatosensory evoked potentials (SEPs) that were recorded using scalp electrodes. Nine healthy adults (21-35 yrs.) were exposed to the IH treatment which involves one-minute sessions of repeated exposures of hypoxic (FIo2= 0.09) and normoxic (FIo2= 0.21) air for 30 minutes. The oxygen saturation level (SpO2) did not drop below 96.6%. This indicated that for the subjects tested the IH treatment failed to produce the marked reduction in the O2 saturation that was observed in spinal cord injured patients. This explains why there was no significant difference in the peak to peak amplitude of the SEPs when comparing the values before with during and after IH (p>0.05; two-tailed paired t-test). Furthermore, the heart rate and blood pressure were monitored and since the SpO2 level did not drop as low as 81% there was no significant change in blood pressure and heart rate following the treatment (p>0.05; two-tailed paired t-test). Under the circumstances that the protocol was not effective we can conclude that it provides a way of creating a sham condition
Experimental and computational studies on the role of single electron transfer in selected organic reactions
Get PDFThis thesis was previously restricted to Strathclyde users only until 1st October 2022.The transition metal-free reaction conditions that couple haloarenes to benzene using a combination of KOtBu and an organic additive is proposed to be initiated by a single electron transfer (SET) into the haloarene. It was initially believed that KOtBu was the electron donor, however mounting experimental evidence suggests that electron donors are formed in situ. Within this thesis, both of these potential initiation pathways are investigated. Experimental evidence is presented to support the proposal that the electron-rich enolate anion 6 (formed by deprotonation of the additive N,N'-dipropylketopiperazine 5) acts as an electron donor (Scheme 1). When the additive 7 was used in the transition metal-free reactions, the cyclised product 10 was isolated, which arose by SET from the enolate anion 8. Computational analysis has shown that when DMF is used as the additive in these transition metal-free reaction conditions, the electron donors, 13 or 14, can form from the dimerisation of the carbamoyl anion of DMF. This work lead towards the development of new additives for these transition metal-free reaction conditions. Computational analysis and experimental evidence is presented that puts into question the previously proposed mechanism that KOtBu can donate a single electron to CBr4 in the bromination of adamantane (Scheme 2). It is proposed that alkoxides, like 16, form hypobromite intermediates when reacted with CBr4 15 (rather than undergoing SET) and these hypohalites have been shown to successfully achieve this transformation. These transition metal-free reaction conditions have been used to achieve SRN1 reactions to couple aryl halides with enolate anions (Scheme 3). A thorough study of the reaction mechanism and possible selectivity of reaction pathways, between SRN1 and aryl-aryl bond formations, was performed. The conclusion is that neither photoactivation nor transition metal-induced activation is needed, and solvent isshown to influence the product selectivity. (Scheme 1 The proposal of the formation electron donors from N,N'-dipropylketopiperazine 5 and DMF 11 that can donate a single electron to haloarenes, such as 1, in the transitionmetal-free coupling reactions. Scheme 2 The formation of radical species from the reaction of alkoxides, like 16, with tetrabromomethane occurs through the formation of hypobromites like 17, as opposed to SET from alkoxide 16, as previously proposed. Scheme 3 Transition metal-free reaction conditions used to activate haloarenes to form arylradicals in SRN1 cyclisation of substrate 22 and analogues.) [Figures for schemes 1, 2 and 3 were not reproducible in abstract.]The transition metal-free reaction conditions that couple haloarenes to benzene using a combination of KOtBu and an organic additive is proposed to be initiated by a single electron transfer (SET) into the haloarene. It was initially believed that KOtBu was the electron donor, however mounting experimental evidence suggests that electron donors are formed in situ. Within this thesis, both of these potential initiation pathways are investigated. Experimental evidence is presented to support the proposal that the electron-rich enolate anion 6 (formed by deprotonation of the additive N,N'-dipropylketopiperazine 5) acts as an electron donor (Scheme 1). When the additive 7 was used in the transition metal-free reactions, the cyclised product 10 was isolated, which arose by SET from the enolate anion 8. Computational analysis has shown that when DMF is used as the additive in these transition metal-free reaction conditions, the electron donors, 13 or 14, can form from the dimerisation of the carbamoyl anion of DMF. This work lead towards the development of new additives for these transition metal-free reaction conditions. Computational analysis and experimental evidence is presented that puts into question the previously proposed mechanism that KOtBu can donate a single electron to CBr4 in the bromination of adamantane (Scheme 2). It is proposed that alkoxides, like 16, form hypobromite intermediates when reacted with CBr4 15 (rather than undergoing SET) and these hypohalites have been shown to successfully achieve this transformation. These transition metal-free reaction conditions have been used to achieve SRN1 reactions to couple aryl halides with enolate anions (Scheme 3). A thorough study of the reaction mechanism and possible selectivity of reaction pathways, between SRN1 and aryl-aryl bond formations, was performed. The conclusion is that neither photoactivation nor transition metal-induced activation is needed, and solvent isshown to influence the product selectivity. (Scheme 1 The proposal of the formation electron donors from N,N'-dipropylketopiperazine 5 and DMF 11 that can donate a single electron to haloarenes, such as 1, in the transitionmetal-free coupling reactions. Scheme 2 The formation of radical species from the reaction of alkoxides, like 16, with tetrabromomethane occurs through the formation of hypobromites like 17, as opposed to SET from alkoxide 16, as previously proposed. Scheme 3 Transition metal-free reaction conditions used to activate haloarenes to form arylradicals in SRN1 cyclisation of substrate 22 and analogues.) [Figures for schemes 1, 2 and 3 were not reproducible in abstract.
Tunable soft matter through peptide self-assembly
Get PDFThis thesis was previously restricted to Strathclyde users only from 1st October 2017 until 15 November 2022.Nanomaterials produced by molecular self-assembly has become one of the emerging technologies for the development of materials for the food, cosmetic and biotechnology industries. These materials exploit the unique properties of their molecular building blocks, which include natural molecules, such as peptides.;Using the entire library of amino acids, consisting of 20 residues that are conserved across all life forms, a range of different materials can be created, such as hydrogels, emulsions, etc. However, such materials are normally found serendipitously or by complex molecular design and therefore the development of new systems has been challenging.;In this thesis, a combination of computational and experimental techniques is used to predict, design, synthesize and apply a range of different tripeptides. Using design rules, a subset of tripeptides was chosen to examine their self-assembling ability. It was determined that peptides with cationic amino acids at the N-terminal position (KYF, KYW and KFF) promote the formation of nanofibers and hydrogelation whereas anionic amino acids form bilayer-like assemblies (DFF and FFD).;Alteration of the peptides sequence disrupts the formation resulting in loss of ordered nanostructures. Exploiting this self-assembling process can result into different materials such as emulsions. Fibrous tripeptide assemblies have the ability to assemble at the water/oil interface stabilizing emulsions via interfacial nanofibrous networks, whereas anionic tripeptide assemblies form surfactant-like emulsifiers.;These materials can be tuned to give different emulsion stabilities. The formation of tripeptides can be controlled using enzymatic methods where physiological conditions can be altered to selectively target different tripeptides. Conditions such as pH and temperature control peptide hydrolysis allowing for the retention of highly order peptide nanostructures.;The promotion of highly order nanostructures is imperative and the presence of additive such as salts can influence the self-assembling structure formed. Different salts can interact with charged amino acids, which promote crosslinking between peptides creating new tripeptide nanomaterials.Nanomaterials produced by molecular self-assembly has become one of the emerging technologies for the development of materials for the food, cosmetic and biotechnology industries. These materials exploit the unique properties of their molecular building blocks, which include natural molecules, such as peptides.;Using the entire library of amino acids, consisting of 20 residues that are conserved across all life forms, a range of different materials can be created, such as hydrogels, emulsions, etc. However, such materials are normally found serendipitously or by complex molecular design and therefore the development of new systems has been challenging.;In this thesis, a combination of computational and experimental techniques is used to predict, design, synthesize and apply a range of different tripeptides. Using design rules, a subset of tripeptides was chosen to examine their self-assembling ability. It was determined that peptides with cationic amino acids at the N-terminal position (KYF, KYW and KFF) promote the formation of nanofibers and hydrogelation whereas anionic amino acids form bilayer-like assemblies (DFF and FFD).;Alteration of the peptides sequence disrupts the formation resulting in loss of ordered nanostructures. Exploiting this self-assembling process can result into different materials such as emulsions. Fibrous tripeptide assemblies have the ability to assemble at the water/oil interface stabilizing emulsions via interfacial nanofibrous networks, whereas anionic tripeptide assemblies form surfactant-like emulsifiers.;These materials can be tuned to give different emulsion stabilities. The formation of tripeptides can be controlled using enzymatic methods where physiological conditions can be altered to selectively target different tripeptides. Conditions such as pH and temperature control peptide hydrolysis allowing for the retention of highly order peptide nanostructures.;The promotion of highly order nanostructures is imperative and the presence of additive such as salts can influence the self-assembling structure formed. Different salts can interact with charged amino acids, which promote crosslinking between peptides creating new tripeptide nanomaterials
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