7103 research outputs found
Sort by
Micro-transfer printing for visible light communications applications
Get PDFThe work presented in this thesis focuses on the transfer printing of InGaN-based blue emitting light emitting diodes (LEDs) onto various non-native substrates for visible light communications applications. The controlled mechanical integration of photonic structures onto non-native substrates using micro-transfer printing (µTP) techniquesis paving the way to high-performance, heterogeneous and multi-functional integrated photonic devices.;2µm-thick 100µm x 100µm LEDs are transfer printed onto these non-native, capability enhancing, substrates using a modified nano-lithography system. Blue-emitting µLEDs in this thin, transfer printable format, were integrated into an array of green-emitting µLEDs to create a dual-colour µLED on a single chip. This chip is then electrically andoptically characterised and demonstrated to examine its potential for data communications applications. The same blue-emitting µLEDs are also integrated with colloidal quantum dot (CQD) colour-converting structures. This yields integrated red, green and orange colour-converting structures all pumped by the blue-emitting transfer printed µLEDs. The µTP technique is finally used to fabricate an integrated optical transceiver device.The work presented in this thesis focuses on the transfer printing of InGaN-based blue emitting light emitting diodes (LEDs) onto various non-native substrates for visible light communications applications. The controlled mechanical integration of photonic structures onto non-native substrates using micro-transfer printing (µTP) techniquesis paving the way to high-performance, heterogeneous and multi-functional integrated photonic devices.;2µm-thick 100µm x 100µm LEDs are transfer printed onto these non-native, capability enhancing, substrates using a modified nano-lithography system. Blue-emitting µLEDs in this thin, transfer printable format, were integrated into an array of green-emitting µLEDs to create a dual-colour µLED on a single chip. This chip is then electrically andoptically characterised and demonstrated to examine its potential for data communications applications. The same blue-emitting µLEDs are also integrated with colloidal quantum dot (CQD) colour-converting structures. This yields integrated red, green and orange colour-converting structures all pumped by the blue-emitting transfer printed µLEDs. The µTP technique is finally used to fabricate an integrated optical transceiver device
Developing predictive models for postoperative complications in cardiac patients
Get PDFA number of cardiac preoperative risk stratification tools have been developed to predict mortality, and less often mortality and morbidity in surgery. Depending on their severity, postoperative complications can have a significant impact on patients' quality of life, hospital length of stay, and healthcare costs and resource usage. Nevertheless, mortality often remains the main 'key performance indicator' used in surgery and is the most commonly reported outcome when evaluating cardiac risk scores.;In this thesis, cardiac data in Golden Jubilee National Hospital was analysed to develop predictive models for postoperative complications in patients undergoing coronary artery bypass graft (CABG), valve, and combined valve and CABG surgery.;All patients undergoing cardiac surgery, recorded in the Golden Jubilee National Hospital CaTHI database between 1st April, 2012 and 31st March, 2016, were analysed.;Three outcomes were investigated: (a) if the patient had postoperative complications, (b) if the patient had severe postoperative complications, and (c) the level of postoperative complications. For each outcome, prediction models were developed, using logistic regression (a, b) and ordinal logistic regression (c). The performance of the models was measured, using receiver operating characteristic (ROC) curves (a, b) and confusion matrices (c), and compared with the performance of the logistic EuroSCORE predicting each outcome.;Of 3700 admissions, 59.7% had CABG, 26.4% valve, and 13.9% combined CABG and valve surgery. Overall, 48.65% of the patients had postoperative complications, with the prevalence of mild complications being 7.05%, moderate 36.65%, and severe complications being 4.95%.;For the model (a) predicting postoperative complications, the area under the ROC curve (AUC) was 0.636 with the sensitivity of 65.7% and specificity of 54.6%. For the model (b) predicting severe postoperative complications, the AUC of the local model was 0.685, with the sensitivity of 86.9% and specificity of 46.8%. The model (c) predicting the level of postoperative complications resulted with the confusion matrix, where the accuracy for predicting no complications was 58%, mild 92%, moderate 63% and severe complications 95%.;Being the most accurate based on AUC, the local model predicting severe complications included eight variables: age, sex, diabetes, left ventricular function, previous cardiac surgery, hypertension, active endocarditis and previous myocardial infarction.;The variables associated with severe complications and the local model predicting severe complications could help the clinicians identify which patients are more likely to have severe complications in order to allocate resources accordingly.A number of cardiac preoperative risk stratification tools have been developed to predict mortality, and less often mortality and morbidity in surgery. Depending on their severity, postoperative complications can have a significant impact on patients' quality of life, hospital length of stay, and healthcare costs and resource usage. Nevertheless, mortality often remains the main 'key performance indicator' used in surgery and is the most commonly reported outcome when evaluating cardiac risk scores.;In this thesis, cardiac data in Golden Jubilee National Hospital was analysed to develop predictive models for postoperative complications in patients undergoing coronary artery bypass graft (CABG), valve, and combined valve and CABG surgery.;All patients undergoing cardiac surgery, recorded in the Golden Jubilee National Hospital CaTHI database between 1st April, 2012 and 31st March, 2016, were analysed.;Three outcomes were investigated: (a) if the patient had postoperative complications, (b) if the patient had severe postoperative complications, and (c) the level of postoperative complications. For each outcome, prediction models were developed, using logistic regression (a, b) and ordinal logistic regression (c). The performance of the models was measured, using receiver operating characteristic (ROC) curves (a, b) and confusion matrices (c), and compared with the performance of the logistic EuroSCORE predicting each outcome.;Of 3700 admissions, 59.7% had CABG, 26.4% valve, and 13.9% combined CABG and valve surgery. Overall, 48.65% of the patients had postoperative complications, with the prevalence of mild complications being 7.05%, moderate 36.65%, and severe complications being 4.95%.;For the model (a) predicting postoperative complications, the area under the ROC curve (AUC) was 0.636 with the sensitivity of 65.7% and specificity of 54.6%. For the model (b) predicting severe postoperative complications, the AUC of the local model was 0.685, with the sensitivity of 86.9% and specificity of 46.8%. The model (c) predicting the level of postoperative complications resulted with the confusion matrix, where the accuracy for predicting no complications was 58%, mild 92%, moderate 63% and severe complications 95%.;Being the most accurate based on AUC, the local model predicting severe complications included eight variables: age, sex, diabetes, left ventricular function, previous cardiac surgery, hypertension, active endocarditis and previous myocardial infarction.;The variables associated with severe complications and the local model predicting severe complications could help the clinicians identify which patients are more likely to have severe complications in order to allocate resources accordingly
The electrical activity of the pulmonary vein and its potential role in cardiac arrhythmia
Get PDFAtrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which is strongly correlated with patients who go on to develop a stroke. AF is thought to be originated in the myocardial sleeve of the pulmonary vein (PV) extending from left atrium (LA). Some studies have shown automaticity activity in PV cardiomyocytes generated by pacemaker-like cells, which can lead to the generation of ectopic activity that initiates AF. Sympathetic and parasympathetic nervous systems play an important role in promoting AF as both a trigger and a substrate. Atrial arrhythmogenic remodelling, defined as any change in atrial structure e.g. mechanical stretch, is considered a critical factor in AF studies. However, the underlying mechanisms for this ectopic activity remain unclear. Thus, the aims of this thesis were to examine the characteristic of cardiomyocytes and nodal cells in the rat PV using Masson's trichrome staining and immunohistochemistry. The role of adrenergic receptors in the PV was investigated with the application of noradrenaline (NA) in a contraction (twitch-tension) study. Moreover, mechanical stretch was also investigated, which changes the electrical activity of the PV potentially leading to the genesis of AF. Histological studies revealed cardiomyocytes extend from LA into the PV, which forms a myocardial sleeve, within which a non-uniform alignment of myocardial fibres was found. Sinoatrial node (SAN) cells were observed in right atrium (RA); however,they were not observed in any area of the rat PV section. Immunohistochemistry was used to identify the expression of HCN4, which is observed in SAN of the RA section but not in the rat PV section. In contractile studies, NA induced ectopic activity in the rat PVs at 37°C, although this ectopic activity decreased when temperature was reduced to 25°C. Increasing extracellular Ca2+ also increased the frequency and the duration of ectopic contractions in the rat PVs. NA-induced ectopic activity in the rat PV was decreased by prazosin, propranolol, carbachol, and verapamil. Mechanical stretch increased the incidence of spontaneous activity but had no effect on the action potential characteristics in rat PV cardiomyocytes. The application of NA increases the incidence of ectopic action potentials, prolongs APD and induces EADs in rat PV cardiomyocytes under a stretch condition. These ectopic action potentials induced bythe combination of stretch and NA were inhibited by gadolinium, ORM-10103, verapamil, prazosin and propranolol in the rat PV myocardium. In conclusion, the PV contains a myocardial sleeve extending from the LA, which is thought to be the source of ectopic electrical activity underlying AF. NA-induced ectopic activity in rat PVs was mediated via α-β-adrenergic receptors, indicating that increased catecholaminergic activity is an important mediator of enhanced automaticity in rat PV cardiomyocytes. Mechanical stretch also induces changes in electrical characteristics, leading to ectopic action potentials in the rat PVs. Stretch activated channels (SACs) may therefore be an important link between stretch and ectopic activity in the PV, potentially acting as a main factor in the development of AF. Thus, autonomic nervous system and structural remodelling in the rat PVs may be considered as an influence on the genesis of arrhythmogenic activity in the development of AF.Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which is strongly correlated with patients who go on to develop a stroke. AF is thought to be originated in the myocardial sleeve of the pulmonary vein (PV) extending from left atrium (LA). Some studies have shown automaticity activity in PV cardiomyocytes generated by pacemaker-like cells, which can lead to the generation of ectopic activity that initiates AF. Sympathetic and parasympathetic nervous systems play an important role in promoting AF as both a trigger and a substrate. Atrial arrhythmogenic remodelling, defined as any change in atrial structure e.g. mechanical stretch, is considered a critical factor in AF studies. However, the underlying mechanisms for this ectopic activity remain unclear. Thus, the aims of this thesis were to examine the characteristic of cardiomyocytes and nodal cells in the rat PV using Masson's trichrome staining and immunohistochemistry. The role of adrenergic receptors in the PV was investigated with the application of noradrenaline (NA) in a contraction (twitch-tension) study. Moreover, mechanical stretch was also investigated, which changes the electrical activity of the PV potentially leading to the genesis of AF. Histological studies revealed cardiomyocytes extend from LA into the PV, which forms a myocardial sleeve, within which a non-uniform alignment of myocardial fibres was found. Sinoatrial node (SAN) cells were observed in right atrium (RA); however,they were not observed in any area of the rat PV section. Immunohistochemistry was used to identify the expression of HCN4, which is observed in SAN of the RA section but not in the rat PV section. In contractile studies, NA induced ectopic activity in the rat PVs at 37°C, although this ectopic activity decreased when temperature was reduced to 25°C. Increasing extracellular Ca2+ also increased the frequency and the duration of ectopic contractions in the rat PVs. NA-induced ectopic activity in the rat PV was decreased by prazosin, propranolol, carbachol, and verapamil. Mechanical stretch increased the incidence of spontaneous activity but had no effect on the action potential characteristics in rat PV cardiomyocytes. The application of NA increases the incidence of ectopic action potentials, prolongs APD and induces EADs in rat PV cardiomyocytes under a stretch condition. These ectopic action potentials induced bythe combination of stretch and NA were inhibited by gadolinium, ORM-10103, verapamil, prazosin and propranolol in the rat PV myocardium. In conclusion, the PV contains a myocardial sleeve extending from the LA, which is thought to be the source of ectopic electrical activity underlying AF. NA-induced ectopic activity in rat PVs was mediated via α-β-adrenergic receptors, indicating that increased catecholaminergic activity is an important mediator of enhanced automaticity in rat PV cardiomyocytes. Mechanical stretch also induces changes in electrical characteristics, leading to ectopic action potentials in the rat PVs. Stretch activated channels (SACs) may therefore be an important link between stretch and ectopic activity in the PV, potentially acting as a main factor in the development of AF. Thus, autonomic nervous system and structural remodelling in the rat PVs may be considered as an influence on the genesis of arrhythmogenic activity in the development of AF
Multimedia motion analysis for remote health monitoring
Get PDFSubstantial amount of research in home-use health monitoring techniques has emerged given growing global health awareness and ageing population in recent decades. These sensor-driven home-use healthcare applications encourage patient involvement at home during daytime activities and nighttime sleep, effectively help assess patients conditions away from clinics and hospitals, and significantly reduce the number of infirmary visits.However, there are two main issues in current wearable/remote sensor-based home-use health monitoring applications: 1) portable human motion analysis systems that are commercially available still require substantial amount of manual effort to process the measurements, which is time consuming and thus impractical for long-term home-use health monitoring, and 2) current sleep-related health monitoring applications are intrusive to the body, limited to measuring the respiration rate and sleep duration, or not clinically validated to demonstrate their efficacy.In this dissertation, we overcome the drawbacks of current health monitoring systems as follows. For lower limb motion analysis, we propose an alternative to state of the art optical motion analysis systems, cost-effective and portable, single-camera system.For upper limb motion analysis, we track all relevant body joints simultaneously, and classify the post-stroke recovery levels based on features extracted from the tracked body-joint trajectories. For abnormal respiratory event detection during sleep, we propose to record video and audio of a patient using a depth camera during his/her sleep, and extract relevant features to train a classifier for detection of the abnormal respiratory events scored manually by a scientific officer based on data collected by a clinical-use sleeping device.The main contribution of this dissertation lies in proposing new application-driven algorithms for advancing cost-effective human limb motion analysis and sleep monitoring healthcare techniques, including an autonomous detection scheme for finding the initial and final frames that are of interest for video analysis, a single marker tracking scheme that is based on the Kalman filter and Structural Similarity image quality assessment,an autonomous gait event detection scheme that is based on the features of the relative positions of the markers, a scheme classification of the post-stroke recovery level by minimization of graph total variation with graph-based signal processing, an alternating-frame depth video coding scheme, a depth video temporal denoising scheme using a motion vector graph smoothness prior, and a dual-ellipse model that can efficiently track the torso motion during a person is sleeping. Experimental results show that, both the autonomous frame-of-interest detection and gait event detection show high detections rates. The validation of tracking in terms of the knee angle, shoulder movement, trunk tilt and elbow movement with a gold standard optical motion analysis system shows R-squared value larger than 0.95. The graph-based classification scheme has the potential to accurately classify participants into different stroke groups. Our depth video coding scheme outperforms a competitor that records only the 8 most significant bits. Our temporal denoising scheme reduces the flickering effect without ever-smoothing. Finally, our trained classifiers can deduce respiratory events with high accuracy. Overall, our proposed limb motion analysis system offers an alternative,inexpensive and convenient solution for clinical gait and upper limb motion analysis,and our proposed sleep monitoring system can reliably detect abnormal respiratory events using our extracted video and audio features.Substantial amount of research in home-use health monitoring techniques has emerged given growing global health awareness and ageing population in recent decades. These sensor-driven home-use healthcare applications encourage patient involvement at home during daytime activities and nighttime sleep, effectively help assess patients conditions away from clinics and hospitals, and significantly reduce the number of infirmary visits.However, there are two main issues in current wearable/remote sensor-based home-use health monitoring applications: 1) portable human motion analysis systems that are commercially available still require substantial amount of manual effort to process the measurements, which is time consuming and thus impractical for long-term home-use health monitoring, and 2) current sleep-related health monitoring applications are intrusive to the body, limited to measuring the respiration rate and sleep duration, or not clinically validated to demonstrate their efficacy.In this dissertation, we overcome the drawbacks of current health monitoring systems as follows. For lower limb motion analysis, we propose an alternative to state of the art optical motion analysis systems, cost-effective and portable, single-camera system.For upper limb motion analysis, we track all relevant body joints simultaneously, and classify the post-stroke recovery levels based on features extracted from the tracked body-joint trajectories. For abnormal respiratory event detection during sleep, we propose to record video and audio of a patient using a depth camera during his/her sleep, and extract relevant features to train a classifier for detection of the abnormal respiratory events scored manually by a scientific officer based on data collected by a clinical-use sleeping device.The main contribution of this dissertation lies in proposing new application-driven algorithms for advancing cost-effective human limb motion analysis and sleep monitoring healthcare techniques, including an autonomous detection scheme for finding the initial and final frames that are of interest for video analysis, a single marker tracking scheme that is based on the Kalman filter and Structural Similarity image quality assessment,an autonomous gait event detection scheme that is based on the features of the relative positions of the markers, a scheme classification of the post-stroke recovery level by minimization of graph total variation with graph-based signal processing, an alternating-frame depth video coding scheme, a depth video temporal denoising scheme using a motion vector graph smoothness prior, and a dual-ellipse model that can efficiently track the torso motion during a person is sleeping. Experimental results show that, both the autonomous frame-of-interest detection and gait event detection show high detections rates. The validation of tracking in terms of the knee angle, shoulder movement, trunk tilt and elbow movement with a gold standard optical motion analysis system shows R-squared value larger than 0.95. The graph-based classification scheme has the potential to accurately classify participants into different stroke groups. Our depth video coding scheme outperforms a competitor that records only the 8 most significant bits. Our temporal denoising scheme reduces the flickering effect without ever-smoothing. Finally, our trained classifiers can deduce respiratory events with high accuracy. Overall, our proposed limb motion analysis system offers an alternative,inexpensive and convenient solution for clinical gait and upper limb motion analysis,and our proposed sleep monitoring system can reliably detect abnormal respiratory events using our extracted video and audio features
A Mie-based flow cytometric size and real refractive index determination method for natural marine particle populations
Get PDFFollowing the path of combining Mie theory and flow cytometry to assign size and refractive index to suspended particles in the steps of Ackleson & Spinrad (1988) and, more recently, Green et al. (2003a, 2003b), a Mie-based flow cytometry (FC) method was developed to retrieve particle size distributions (PSDs) and real refractive index (rRI) information in natural waters. The need for a technique capable of directly assessing both size and real refractive index of the particles was first established by carrying out a sensitivity analysis of the effect a spectrally complex refractive index and log-normal variations to commonly employed PSD models have on the optical behaviour of the particle population. The Mie-based FC method proper was then developed and tested, initially against standard particles of known diameter and rRI and secondly on two datasets, one of algal culture samples (AC dataset) and one of natural seawater samples collected in UK coastal waters (UKCW dataset).The method retrieved PSDs and real refractive index distributions (PRIDs) for both datasets. FC PSDs were validated against known algal sizes for AC samples and against independent PSDs measured via laser diffractometry for UKCW samples. PRIDs were then combined with FC PSDs and fed into Mie-based forward optical modelling to reconstruct bulk IOPs. These achieved broad agreement with independent IOP measurements, lending further support to the results of the FC method and to the employment of Mie theory within the context of optical modelling of natural particle populations. Furthermore, the unique insight offered by the FC method in terms of PSD and PRID determination allowed for the assessment of the individual contribution of particle subpopulations to the bulk IOPs, both by size (small/large particle fractions) and by particle type (inorganic/organic/fluorescent fractions). Lastly, PSDs and PRIDs were combined with literature-derived models of particle density, cell organic carbon and chlorophyll-A content, in an effort to explore the biogeochemical properties of the particle populations within the UKCW dataset. The models successfully estimated independent measurements of particulate suspended matter and (after an optimisation procedure) of organic carbon and chlorophyll-A content.Following the path of combining Mie theory and flow cytometry to assign size and refractive index to suspended particles in the steps of Ackleson & Spinrad (1988) and, more recently, Green et al. (2003a, 2003b), a Mie-based flow cytometry (FC) method was developed to retrieve particle size distributions (PSDs) and real refractive index (rRI) information in natural waters. The need for a technique capable of directly assessing both size and real refractive index of the particles was first established by carrying out a sensitivity analysis of the effect a spectrally complex refractive index and log-normal variations to commonly employed PSD models have on the optical behaviour of the particle population. The Mie-based FC method proper was then developed and tested, initially against standard particles of known diameter and rRI and secondly on two datasets, one of algal culture samples (AC dataset) and one of natural seawater samples collected in UK coastal waters (UKCW dataset).The method retrieved PSDs and real refractive index distributions (PRIDs) for both datasets. FC PSDs were validated against known algal sizes for AC samples and against independent PSDs measured via laser diffractometry for UKCW samples. PRIDs were then combined with FC PSDs and fed into Mie-based forward optical modelling to reconstruct bulk IOPs. These achieved broad agreement with independent IOP measurements, lending further support to the results of the FC method and to the employment of Mie theory within the context of optical modelling of natural particle populations. Furthermore, the unique insight offered by the FC method in terms of PSD and PRID determination allowed for the assessment of the individual contribution of particle subpopulations to the bulk IOPs, both by size (small/large particle fractions) and by particle type (inorganic/organic/fluorescent fractions). Lastly, PSDs and PRIDs were combined with literature-derived models of particle density, cell organic carbon and chlorophyll-A content, in an effort to explore the biogeochemical properties of the particle populations within the UKCW dataset. The models successfully estimated independent measurements of particulate suspended matter and (after an optimisation procedure) of organic carbon and chlorophyll-A content
Development of an NMR method for the In vitro characterisation of enzyme activity present in honey bee venom against mammalian bioactive molecules
Get PDFThis thesis was previously restricted to Strathclyde users only from 1st December 2017 until 1st December 2022.The venoms of snakes and insects are complex mixtures of toxins and enzymes that produce profound physiological and behavioural consequences when injected into prey creatures. Understanding how these consequences are achieved from very small amounts of venom in short time intervals sheds light on the principles of venom action and the defence mechanisms that may have to be overcome. In addition to the possibility of better treatments for envenomed humans, wider insights into drug discovery are also promised.;This thesis describes an investigation into the chemical effects of Honey Bee (Apis mellifera) venom. The toxic effects of some bee venom components (such as melittin and phospholipase A2) are well known, but the venom's capacity to respond to potential defensive reactions (as represented by the biomolecules commonly released by mammals in response to wounding and the injection of toxins) has not been so well studied.;Using the technique of Real-time NMR, specially adapted to this research, purified whole bee venom was challenged with a range of bioactive molecules that a mammalian victim could potentially release in response to the presence of the venom (i.e. adrenalin, cortisol, angiotensin, bradykinin, substance P and opioid peptides).;Reactions were carried out in the NMR spectrometer under physiological conditions (pH 7.4, 37°C) and full spectrum "snapshots" were taken at frequent intervals. Subsequent analysis revealed whether or not any transformation had taken place, and, if so, what intermediates and products were generated. It was found that only substance P and the opioid peptides were acted upon by the bee venom, implying the venom contained one or more appropriate peptidase activities.;Further experimentation with the opioids Met- and Leu-enkephalin, and their N-terminal fragment Tyr-Gly-Gly, established that the peptidase activity was primarily that of a dipeptidyl dipeptidase, supported by a dipeptidase. Subsequent kinetic studies implied that these substrates were not ideal and so other opioid peptides (Endomorphin I, Endomorphin II and Casomorphin 1-7) were also tested. It was found that Endomorphin I was the "best" substrate.;The substrate specificity of the venom dipeptidyl peptidase shows consistencies with the known mammalian dipeptidyl peptidases III and IV. The presence of a DPP IV - like enzyme (i.e. an evolutionary homologue of the human version) in bee venom has been predicted from gene sequence analysis and the generation of melittin from its precursor. This bee protein is also known as Api m 5 and is a notable allergen. Consequently, the bee venom was challenged with a model substrate and a model inhibitor for human DPP IV.;The model substrate was readily converted and the model inhibitor reduced the rate of conversion of the opioid peptides. Two synthetic variants of the inhibitor were tested, but they were not as effective. Although bee venom Api m 5 shares structural and preferred substrate/inhibitor similarities with human DPP IV, some contrasts remain (for example the former's ability to act on enkephalin peptides).;It is proposed that the role of the bee venom DPP-IV like enzyme (i.e. Api m 5) is primarily to destroy opioid peptides released by mammalian sting victims in response to the physical and toxicological impact of the venom. Opioid peptides bind to skin nociceptors to limit pain perception following injury, so fragmentation of these peptides could lead to prolonged pain from the sting site(s) and therefore behaviour that serves the interests of the bees (i.e. avoidance, retreat or stopping in the case of a mammal foraging a hive).;Preliminary experiments were conducted to follow the action of the hyaluronidase in bee venom which breaks up the extra cellular matrix carbohydrate to speed up the tissue spread of the venom components. The NMR method again proved to be useful.The venoms of snakes and insects are complex mixtures of toxins and enzymes that produce profound physiological and behavioural consequences when injected into prey creatures. Understanding how these consequences are achieved from very small amounts of venom in short time intervals sheds light on the principles of venom action and the defence mechanisms that may have to be overcome. In addition to the possibility of better treatments for envenomed humans, wider insights into drug discovery are also promised.;This thesis describes an investigation into the chemical effects of Honey Bee (Apis mellifera) venom. The toxic effects of some bee venom components (such as melittin and phospholipase A2) are well known, but the venom's capacity to respond to potential defensive reactions (as represented by the biomolecules commonly released by mammals in response to wounding and the injection of toxins) has not been so well studied.;Using the technique of Real-time NMR, specially adapted to this research, purified whole bee venom was challenged with a range of bioactive molecules that a mammalian victim could potentially release in response to the presence of the venom (i.e. adrenalin, cortisol, angiotensin, bradykinin, substance P and opioid peptides).;Reactions were carried out in the NMR spectrometer under physiological conditions (pH 7.4, 37°C) and full spectrum "snapshots" were taken at frequent intervals. Subsequent analysis revealed whether or not any transformation had taken place, and, if so, what intermediates and products were generated. It was found that only substance P and the opioid peptides were acted upon by the bee venom, implying the venom contained one or more appropriate peptidase activities.;Further experimentation with the opioids Met- and Leu-enkephalin, and their N-terminal fragment Tyr-Gly-Gly, established that the peptidase activity was primarily that of a dipeptidyl dipeptidase, supported by a dipeptidase. Subsequent kinetic studies implied that these substrates were not ideal and so other opioid peptides (Endomorphin I, Endomorphin II and Casomorphin 1-7) were also tested. It was found that Endomorphin I was the "best" substrate.;The substrate specificity of the venom dipeptidyl peptidase shows consistencies with the known mammalian dipeptidyl peptidases III and IV. The presence of a DPP IV - like enzyme (i.e. an evolutionary homologue of the human version) in bee venom has been predicted from gene sequence analysis and the generation of melittin from its precursor. This bee protein is also known as Api m 5 and is a notable allergen. Consequently, the bee venom was challenged with a model substrate and a model inhibitor for human DPP IV.;The model substrate was readily converted and the model inhibitor reduced the rate of conversion of the opioid peptides. Two synthetic variants of the inhibitor were tested, but they were not as effective. Although bee venom Api m 5 shares structural and preferred substrate/inhibitor similarities with human DPP IV, some contrasts remain (for example the former's ability to act on enkephalin peptides).;It is proposed that the role of the bee venom DPP-IV like enzyme (i.e. Api m 5) is primarily to destroy opioid peptides released by mammalian sting victims in response to the physical and toxicological impact of the venom. Opioid peptides bind to skin nociceptors to limit pain perception following injury, so fragmentation of these peptides could lead to prolonged pain from the sting site(s) and therefore behaviour that serves the interests of the bees (i.e. avoidance, retreat or stopping in the case of a mammal foraging a hive).;Preliminary experiments were conducted to follow the action of the hyaluronidase in bee venom which breaks up the extra cellular matrix carbohydrate to speed up the tissue spread of the venom components. The NMR method again proved to be useful
The resistance of functionalised PET samples to hydrolytic degradation
Get PDFCD contains appendices.It is well documented in the literature that poly(ethylene terephthalate) (PET) undergoes hydrolysis. PET has been previously used in short lifetime applications such as food packaging and textile fibers. The condition that PET is exposed to when used in these applications allows hydrolysis to occur very slowly, and so does not cause any concern. In recent years PET has been considered for more long term outdoor applications such as use in solar cells. In these applications, it is a concern that PET is a hydrolysis sensitive polymer.One of the tried and tested ways to reduce the impact of hydrolytic degradation is to involve lowering the carboxyl end group concentration. An esterification reaction between PET and epoxides will successfully lower the carboxyl end group concentration. Three epoxides were investigated, namely; Cardura, Heloxy and Vikolox.Reliable titration and nuclear magnetic resonance (NMR) methods were utilised during this PhD to detect the esterification reaction and how quickly it was occurring. All three epoxides were shown to be subjected to the esterification reaction with the model compounds benzoic acid and poly(ethylene isophthalate) (PEI). Cardura, however, was shown to have a greater extent of reaction with carboxyl end groups than the other epoxides. The NMR data obtained for the 3 epoxides clearly show that a higher level of esterification reaction is occurring in Cardura when compared to Heloxy and Vikolox (after 1 minute at 150 oC, all epoxide groups were reacted in the Cardura samples, whereas no reaction was detected in the other 2 epoxide samples).;DuPont Teijin Films (DTF) requires the additive they will use to be capable of being manufactured in a reactive extrusion process. Their current processing lines could be easily modified to include a liquid feed, preventing the substantial capital costs that would otherwise be required to manufacture the new product. A small scale system was established to determine if the selected additives could be added in this way; all three epoxides could successfully be added in this manner. Though all three epoxides could be added, the carboxylic end group concentration of the PET samples containing Cardura was reduced the most. With the addition of 6% Cardura the carboxylic acid was reduced from 41.54 to 7.56 equivalence per 106 grams, but was only reduced to 17.28 and 18.02 equivalents per 106 grams for samples of PET containing 6% Heloxy and 6% Vikolox respectively. The fact that the carboxyl end group concentration of the samples containing Cardura is significantly lower allows Cardura to be added in a lower concentration, which is desired in order to minimise raw material costs.For Cardura to be a suitable additive, it must display extrusion stability when exposed to various conditions. Additionally, the chosen additive must not have any adverse effects on the polymer samples properties such as clarity, molecular weight, crystallinity and melting point. Cardura was shown to have good extrusion stability and no adverse effect on the polymer sample. Cardura was shown to increase the resistance to hydrolytic degradation but to not have any adverse effects on the thermal or thermal-oxidative degradation of the polymer samples. The data gathered in this thesis indicates that Cardura could be utilised to increase the resistance of PET to hydrolytic degradation in long term outdoor applications such as solar cells.It is well documented in the literature that poly(ethylene terephthalate) (PET) undergoes hydrolysis. PET has been previously used in short lifetime applications such as food packaging and textile fibers. The condition that PET is exposed to when used in these applications allows hydrolysis to occur very slowly, and so does not cause any concern. In recent years PET has been considered for more long term outdoor applications such as use in solar cells. In these applications, it is a concern that PET is a hydrolysis sensitive polymer.One of the tried and tested ways to reduce the impact of hydrolytic degradation is to involve lowering the carboxyl end group concentration. An esterification reaction between PET and epoxides will successfully lower the carboxyl end group concentration. Three epoxides were investigated, namely; Cardura, Heloxy and Vikolox.Reliable titration and nuclear magnetic resonance (NMR) methods were utilised during this PhD to detect the esterification reaction and how quickly it was occurring. All three epoxides were shown to be subjected to the esterification reaction with the model compounds benzoic acid and poly(ethylene isophthalate) (PEI). Cardura, however, was shown to have a greater extent of reaction with carboxyl end groups than the other epoxides. The NMR data obtained for the 3 epoxides clearly show that a higher level of esterification reaction is occurring in Cardura when compared to Heloxy and Vikolox (after 1 minute at 150 oC, all epoxide groups were reacted in the Cardura samples, whereas no reaction was detected in the other 2 epoxide samples).;DuPont Teijin Films (DTF) requires the additive they will use to be capable of being manufactured in a reactive extrusion process. Their current processing lines could be easily modified to include a liquid feed, preventing the substantial capital costs that would otherwise be required to manufacture the new product. A small scale system was established to determine if the selected additives could be added in this way; all three epoxides could successfully be added in this manner. Though all three epoxides could be added, the carboxylic end group concentration of the PET samples containing Cardura was reduced the most. With the addition of 6% Cardura the carboxylic acid was reduced from 41.54 to 7.56 equivalence per 106 grams, but was only reduced to 17.28 and 18.02 equivalents per 106 grams for samples of PET containing 6% Heloxy and 6% Vikolox respectively. The fact that the carboxyl end group concentration of the samples containing Cardura is significantly lower allows Cardura to be added in a lower concentration, which is desired in order to minimise raw material costs.For Cardura to be a suitable additive, it must display extrusion stability when exposed to various conditions. Additionally, the chosen additive must not have any adverse effects on the polymer samples properties such as clarity, molecular weight, crystallinity and melting point. Cardura was shown to have good extrusion stability and no adverse effect on the polymer sample. Cardura was shown to increase the resistance to hydrolytic degradation but to not have any adverse effects on the thermal or thermal-oxidative degradation of the polymer samples. The data gathered in this thesis indicates that Cardura could be utilised to increase the resistance of PET to hydrolytic degradation in long term outdoor applications such as solar cells
The development of natural products as phytotoxic leads for herbicide discovery
Get PDFEffective agrochemicals are essential to maintaining sustainable agriculture to support a growing population. Herbicide resistance is an ever increasing problem, and in order to combat this there is a requirement for the introduction of new herbicidal agents with novel modes of action. Natural products serve as an abundant source of structurally diverse phytotoxins, which typically have novel modes of action in comparison with their synthetic counterparts. The natural product coronatine (COR), isolated from Pseudomonas syringae, has been a compound of interest to the agrochemical community since its isolation and elucidation of its phytotoxic properties. Through the industry/academia collaboration described in this thesis, coronatine is now a tractable target for a structure-activity relationship (SAR) campaign. Through the development of a scalable synthesis of the COR polyketide fragment, coronafacic acid (CFA), a diverse array of N-coronafacoyl-amino acid analogues were synthesised. The inherent flexibility of the synthesis, imparted by its convergent nature, has enabled the synthesis of several CFA analogues, featuring single point changes to the parent scaffold. In the complementary study, scalable synthesis of the COR amino acid moiety, coronamic acid (CMA), enabled diverse screening of analogues where the core moiety was varied. Through the biological evaluation of these compounds, an SAR for herbicidal activity around the COR scaffold has been identified. Initial efforts focused on modification of the amino acid component, however work in this area failed to afford any compounds of significant activity. Retention of the COR amino acid moiety, CMA, with modification of the CFA core has generated several COR analogues with good levels of potency. On analysis of this data set and supporting computational docking, we have concluded that the key convenor of potency in COR is the amino acid fragment, CMA. The CFA moiety appears to be comparatively more amenable to structural modification with the retention of potency, and we suggest that further SAR studies of the COR scaffold focus on analogues of this unit.Effective agrochemicals are essential to maintaining sustainable agriculture to support a growing population. Herbicide resistance is an ever increasing problem, and in order to combat this there is a requirement for the introduction of new herbicidal agents with novel modes of action. Natural products serve as an abundant source of structurally diverse phytotoxins, which typically have novel modes of action in comparison with their synthetic counterparts. The natural product coronatine (COR), isolated from Pseudomonas syringae, has been a compound of interest to the agrochemical community since its isolation and elucidation of its phytotoxic properties. Through the industry/academia collaboration described in this thesis, coronatine is now a tractable target for a structure-activity relationship (SAR) campaign. Through the development of a scalable synthesis of the COR polyketide fragment, coronafacic acid (CFA), a diverse array of N-coronafacoyl-amino acid analogues were synthesised. The inherent flexibility of the synthesis, imparted by its convergent nature, has enabled the synthesis of several CFA analogues, featuring single point changes to the parent scaffold. In the complementary study, scalable synthesis of the COR amino acid moiety, coronamic acid (CMA), enabled diverse screening of analogues where the core moiety was varied. Through the biological evaluation of these compounds, an SAR for herbicidal activity around the COR scaffold has been identified. Initial efforts focused on modification of the amino acid component, however work in this area failed to afford any compounds of significant activity. Retention of the COR amino acid moiety, CMA, with modification of the CFA core has generated several COR analogues with good levels of potency. On analysis of this data set and supporting computational docking, we have concluded that the key convenor of potency in COR is the amino acid fragment, CMA. The CFA moiety appears to be comparatively more amenable to structural modification with the retention of potency, and we suggest that further SAR studies of the COR scaffold focus on analogues of this unit
Stick with me! : how effective and lasting helping relationships support the educational experience of children looked after at home in Scotland
Get PDFHome Supervision is a method regularly used in Scotland to support vulnerable children and families in their homes. Such children and their families are 'looked after' by local authorities and supported by allocated social workers. However, this cohort of young people has poorer educational outcomes compared with other looked after children. There is little in the way of research to explore why this is the case. This study seeks to address a gap in the literature by exploring issues of education and support from the perspectives of young people themselves.The research was undertaken with 15 young people, in three different geographical areas of Scotland using semi-structured interviews. Each initial interview was analysed and informed the production of a digital interactive presentation. Each presentation was shared with the young people to review and discuss the understanding of the content gleaned from the first interview and to act as a prompt for the second interview. Interviews were transcribed and the data coded, based on key themes for each person. Thereafter, summaries were written up and cross-cutting themes identified. These included:relationships with teachers and social workers; issues caused by transition; the benefits of coaching and mentoring; and issues caused by a lack of continuity of relationships.The study revealed that young people were more likely to struggle with their education during the transition from primary to secondary school. The study reinforced the degree to which young people under Home Supervision experience considerable disruption and change in their education and stability. They are more likely to trust their teachers than social workers when dealing with challenges and issues in their lives and are likely to experience isolation from voluntary community-based services.Mentors and coaches have a major role to play in supporting young people and encouraging resilience using informal youth work approaches. By acting as trusted supporters, they can help foster both confidence and social capital for the young people they support by assisting them to access relevant services and navigate bureaucratic systems and procedures such as children's hearings and employment.The current lack of continuity of professional relationship experienced by many children and young people who have a Home Supervision requirement, combined with the disparity in resources and services provided for them, are barriers that require to be addressed if Home Supervision is to be an effective support intervention for vulnerable children and young people.Home Supervision is a method regularly used in Scotland to support vulnerable children and families in their homes. Such children and their families are 'looked after' by local authorities and supported by allocated social workers. However, this cohort of young people has poorer educational outcomes compared with other looked after children. There is little in the way of research to explore why this is the case. This study seeks to address a gap in the literature by exploring issues of education and support from the perspectives of young people themselves.The research was undertaken with 15 young people, in three different geographical areas of Scotland using semi-structured interviews. Each initial interview was analysed and informed the production of a digital interactive presentation. Each presentation was shared with the young people to review and discuss the understanding of the content gleaned from the first interview and to act as a prompt for the second interview. Interviews were transcribed and the data coded, based on key themes for each person. Thereafter, summaries were written up and cross-cutting themes identified. These included:relationships with teachers and social workers; issues caused by transition; the benefits of coaching and mentoring; and issues caused by a lack of continuity of relationships.The study revealed that young people were more likely to struggle with their education during the transition from primary to secondary school. The study reinforced the degree to which young people under Home Supervision experience considerable disruption and change in their education and stability. They are more likely to trust their teachers than social workers when dealing with challenges and issues in their lives and are likely to experience isolation from voluntary community-based services.Mentors and coaches have a major role to play in supporting young people and encouraging resilience using informal youth work approaches. By acting as trusted supporters, they can help foster both confidence and social capital for the young people they support by assisting them to access relevant services and navigate bureaucratic systems and procedures such as children's hearings and employment.The current lack of continuity of professional relationship experienced by many children and young people who have a Home Supervision requirement, combined with the disparity in resources and services provided for them, are barriers that require to be addressed if Home Supervision is to be an effective support intervention for vulnerable children and young people
DC-DC converter designs for medium and high voltage direct current systems
Get PDFDC fault protection is one challenge impeding the development of multi-terminal dc grids. The absence of manufacturing and operational standards has led to many point-to-point HVDC links built at different voltage levels, which creates another challenge. Therefore, the issues of voltage matching and dc fault isolation in high voltage dc systems are undergoing extensive research and are the focus of this thesis. The modular multilevel design of dual active bridge (DAB) converters is analysed in light of state-of-the-art research in the field. The multilevel DAB structure is meant to serve medium and high voltage applications. The modular design facilitates scalability in terms of manufacturing and installation, and permits the generation of an output voltage with controllable dv/dt. The modular design is realized by connecting an auxiliary soft voltage clamping circuit across each semiconductor switch (for instance insulated gate bipolar transistor - IGBT) of the series switch arrays in the conventional two-level DAB design. With auxiliary active circuits, series connected IGBTs effectively become series connection of half-bridge submodules (cells) in each arm, resembling the modular multilevel converter (MMC) structure. For each half-bridge cell, capacitance for quasi-square wave (quasi two- level) operation is significantly smaller than typical capacitance used in MMCs. Also, no bulky arm inductors are needed. Consequently, the footprint, volume, weight and cost of cells are lower. Four switching sequences are proposed and analysed in terms of switching losses and operation aspects. A design method to size converter components is proposed and validated. Soft-switching characteristics of the analysed DAB are found comparable to the case of a two-level DAB at the same ratings and conditions. A family of designs derived from the proposed DAB design are studied in depth. Depending on the individual structure, they may offer further advantages in term of installed semiconductor power, energy storage, conduction losses, or footprint. A non-isolated dc-dc converter topology which offers more compact and efficient station design with respect to isolated DAB - yet without galvanic isolation - is studied for quasi two-level (trapezoidal) operation and compared to the isolated versions. In all the proposed isolated designs, active control of the dc-dc converter facilitates dc voltage regulation and near instant isolation of pole-to-pole and pole-to-ground dc faults within its protection zone. The same can be achieved for the considered non-isolated dc-dc converter topology with additional installed semiconductors. Simulation and experimental results are presented to substantiate the proposed concepts.DC fault protection is one challenge impeding the development of multi-terminal dc grids. The absence of manufacturing and operational standards has led to many point-to-point HVDC links built at different voltage levels, which creates another challenge. Therefore, the issues of voltage matching and dc fault isolation in high voltage dc systems are undergoing extensive research and are the focus of this thesis. The modular multilevel design of dual active bridge (DAB) converters is analysed in light of state-of-the-art research in the field. The multilevel DAB structure is meant to serve medium and high voltage applications. The modular design facilitates scalability in terms of manufacturing and installation, and permits the generation of an output voltage with controllable dv/dt. The modular design is realized by connecting an auxiliary soft voltage clamping circuit across each semiconductor switch (for instance insulated gate bipolar transistor - IGBT) of the series switch arrays in the conventional two-level DAB design. With auxiliary active circuits, series connected IGBTs effectively become series connection of half-bridge submodules (cells) in each arm, resembling the modular multilevel converter (MMC) structure. For each half-bridge cell, capacitance for quasi-square wave (quasi two- level) operation is significantly smaller than typical capacitance used in MMCs. Also, no bulky arm inductors are needed. Consequently, the footprint, volume, weight and cost of cells are lower. Four switching sequences are proposed and analysed in terms of switching losses and operation aspects. A design method to size converter components is proposed and validated. Soft-switching characteristics of the analysed DAB are found comparable to the case of a two-level DAB at the same ratings and conditions. A family of designs derived from the proposed DAB design are studied in depth. Depending on the individual structure, they may offer further advantages in term of installed semiconductor power, energy storage, conduction losses, or footprint. A non-isolated dc-dc converter topology which offers more compact and efficient station design with respect to isolated DAB - yet without galvanic isolation - is studied for quasi two-level (trapezoidal) operation and compared to the isolated versions. In all the proposed isolated designs, active control of the dc-dc converter facilitates dc voltage regulation and near instant isolation of pole-to-pole and pole-to-ground dc faults within its protection zone. The same can be achieved for the considered non-isolated dc-dc converter topology with additional installed semiconductors. Simulation and experimental results are presented to substantiate the proposed concepts
Access Repository Dashboard
Do you manage STAX (Strathclyde Repository)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!