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Big Data Technologies CS982 exam papers
No full textAccess restricted to staff and registered students of the University of Strathclyde.PAST EXAM PAPERS ARE NO LONGER BEING ADDED TO STAX. PLEASE VISIT SUPRIMO TO ACCESS AN UP-TO-DATE COLLECTION OF PAST EXAM PAPERS: https://suprimo.lib.strath.ac.uk
Investigating the link between symptoms of sleep disturbance and subsequent self-harm risk during adolescence
Get PDFThis thesis was previously held under moratorium from 2nd November 2020 until 2nd November 2022.Adolescence represents a high-risk period for the onset and repetition of selfharm, and evidence suggests that an increasing number of young people are harming themselves. This is concerning as self-harm is indicative of intolerable psychological distress, and young people who harm themselves are at greater risk of suicide in the future. Responding effectively to self-harm is a key component of suicide prevention efforts. A fundamental step in reducing self-harm during adolescence is the identification of factors associated with increased self-harm risk, and clarification regarding the theoretical underpinnings of these relationships. Increased attention has been placed on adolescent sleep within this context, and research evidence supports a role for symptoms of sleep disturbance within pathways to self-harm. However, important questions about this relationship remain unanswered. This thesis aimed to target key gaps in current understanding, and had two overarching aims. The first aim of this thesis was to provide a more detailed and nuanced understanding the association between specific symptoms of sleep disturbance and future self-harm risk in order to understand which aspects of sleep are driving the relationship. The second aim was to examine the role of theoretically salient psychological factors, which underpin the relationship between disturbed sleep and self-harm in order to understand why the link exists. These aims were addressed by conducting a programme of research including a systematic review, a six-month prospective study, and a micro-longitudinal investigation. Chapter 3 synthesises and critically evaluates research examining the link between symptoms of sleep disturbance and self-harm risk during adolescence. Global assessments of sleep disturbance, symptoms of sleep disorders and problems, and specific sleep parameters, are all associated with increased vulnerability to self-harming and suicidal thoughts and behaviours. A research agenda is presented offering recommended directions for future work in the area. Chapter 4 details a six-month prospective study that examines the relationship between a wide range of symptoms of sleep disturbance and subsequent self-harm thoughts and behaviours. Clinically salient insomnia symptoms were prospectively associated with self-ham thoughts. Both insomnia symptoms and poor sleep quality predicted that a young person would engage in first time or repeat self-harm during the six-month follow up period. To establish why this link exists, Chapter 5 examined whether psychological pathways - derived from the Integrated Motivational Volitional Model of Suicidal Behaviour - explain the link between insomnia symptoms and selfharm risk. The relationship was accounted for by perceptions of defeat and internal entrapment (but not external entrapment). Chapter 6 details a micro-longitudinalinvestigation that aimed to build on the insights gained from the systematic review and six-month prospective study, by examining whether symptoms of sleep disturbance and psychological factors (i.e., defeat, internal entrapment, and externalentrapment) predicted short-term self-harm risk. Specific symptoms of sleep disturbance predicted defeat (sleep quality) and internal entrapment (nightmare intensity and distress) the following day, but were not associated with next-day selfharm thoughts and behaviours. Taken together, the research presented in this thesis provides novel insights into the relationship between sleep disturbance and self-harm risk within the unique context of adolescence. This advanced understanding has implications for future research, theoretical conceptualisation of self-harm risk, and has the potential to guide policy and prevention efforts.Adolescence represents a high-risk period for the onset and repetition of selfharm, and evidence suggests that an increasing number of young people are harming themselves. This is concerning as self-harm is indicative of intolerable psychological distress, and young people who harm themselves are at greater risk of suicide in the future. Responding effectively to self-harm is a key component of suicide prevention efforts. A fundamental step in reducing self-harm during adolescence is the identification of factors associated with increased self-harm risk, and clarification regarding the theoretical underpinnings of these relationships. Increased attention has been placed on adolescent sleep within this context, and research evidence supports a role for symptoms of sleep disturbance within pathways to self-harm. However, important questions about this relationship remain unanswered. This thesis aimed to target key gaps in current understanding, and had two overarching aims. The first aim of this thesis was to provide a more detailed and nuanced understanding the association between specific symptoms of sleep disturbance and future self-harm risk in order to understand which aspects of sleep are driving the relationship. The second aim was to examine the role of theoretically salient psychological factors, which underpin the relationship between disturbed sleep and self-harm in order to understand why the link exists. These aims were addressed by conducting a programme of research including a systematic review, a six-month prospective study, and a micro-longitudinal investigation. Chapter 3 synthesises and critically evaluates research examining the link between symptoms of sleep disturbance and self-harm risk during adolescence. Global assessments of sleep disturbance, symptoms of sleep disorders and problems, and specific sleep parameters, are all associated with increased vulnerability to self-harming and suicidal thoughts and behaviours. A research agenda is presented offering recommended directions for future work in the area. Chapter 4 details a six-month prospective study that examines the relationship between a wide range of symptoms of sleep disturbance and subsequent self-harm thoughts and behaviours. Clinically salient insomnia symptoms were prospectively associated with self-ham thoughts. Both insomnia symptoms and poor sleep quality predicted that a young person would engage in first time or repeat self-harm during the six-month follow up period. To establish why this link exists, Chapter 5 examined whether psychological pathways - derived from the Integrated Motivational Volitional Model of Suicidal Behaviour - explain the link between insomnia symptoms and selfharm risk. The relationship was accounted for by perceptions of defeat and internal entrapment (but not external entrapment). Chapter 6 details a micro-longitudinalinvestigation that aimed to build on the insights gained from the systematic review and six-month prospective study, by examining whether symptoms of sleep disturbance and psychological factors (i.e., defeat, internal entrapment, and externalentrapment) predicted short-term self-harm risk. Specific symptoms of sleep disturbance predicted defeat (sleep quality) and internal entrapment (nightmare intensity and distress) the following day, but were not associated with next-day selfharm thoughts and behaviours. Taken together, the research presented in this thesis provides novel insights into the relationship between sleep disturbance and self-harm risk within the unique context of adolescence. This advanced understanding has implications for future research, theoretical conceptualisation of self-harm risk, and has the potential to guide policy and prevention efforts
The fiction of Anita Brookner : persona, reception, and literary value
Get PDFPreviously held under moratorium from 6th April 2021 until 6th April 2023This thesis considers Anita Brookner’s career in fiction from the perspective of three interdependent characteristics of the public author (persona, reception, and canon) in order to determine the author’s place within contemporary literary history, as well as determine how and why this placement was so uncertain in her lifetime. To do so, theories of intertextuality – Gérard Genette’s theory of transtextuality in particular – are applied to a number of Brookner’s narratives, as well as a variety of paratexts, including her book covers, titles, and dedications. Focussing first on her earliest novels, this thesis demonstrates the extent to which Brookner developed an ironic, self-reflexive persona with a sustained interest in explicit intertextualities. This is followed by a detailed reading of her most well-known novel Hotel du Lac that positions Brookner as writing self-pastiche, a complex mode of satire Genette describes in Palimpsests: Literature in the Second Degree. Then, a comprehensive analysis of the 1984 Booker Prize ceremony proceedings – and the heightened publicity she received as a result of winning it – is conducted to show how a decontextualized reading of the novel was able to emerge. However, when the novel is read in context, it is suggested that Brookner, like Angela Carter, can be understood as writing in a tradition of ‘postmodernism and feminism,’ outside and between both categories. The thesis further considers the relationships between the author and canonicity, with an emphasis on how she was portrayed in educational materials that placed personality to the forefront, and in a film adaptation that deadened her irony. The first extended study of Brookner’s career in its entirety, this thesis also seeks to convey how fiction is produced and consumed in our contemporary era, with recurring reference to the publishing and bookselling industries, critical theory, and how our culture’s ambivalent responses to death can figure in the life of the author.This thesis considers Anita Brookner’s career in fiction from the perspective of three interdependent characteristics of the public author (persona, reception, and canon) in order to determine the author’s place within contemporary literary history, as well as determine how and why this placement was so uncertain in her lifetime. To do so, theories of intertextuality – Gérard Genette’s theory of transtextuality in particular – are applied to a number of Brookner’s narratives, as well as a variety of paratexts, including her book covers, titles, and dedications. Focussing first on her earliest novels, this thesis demonstrates the extent to which Brookner developed an ironic, self-reflexive persona with a sustained interest in explicit intertextualities. This is followed by a detailed reading of her most well-known novel Hotel du Lac that positions Brookner as writing self-pastiche, a complex mode of satire Genette describes in Palimpsests: Literature in the Second Degree. Then, a comprehensive analysis of the 1984 Booker Prize ceremony proceedings – and the heightened publicity she received as a result of winning it – is conducted to show how a decontextualized reading of the novel was able to emerge. However, when the novel is read in context, it is suggested that Brookner, like Angela Carter, can be understood as writing in a tradition of ‘postmodernism and feminism,’ outside and between both categories. The thesis further considers the relationships between the author and canonicity, with an emphasis on how she was portrayed in educational materials that placed personality to the forefront, and in a film adaptation that deadened her irony. The first extended study of Brookner’s career in its entirety, this thesis also seeks to convey how fiction is produced and consumed in our contemporary era, with recurring reference to the publishing and bookselling industries, critical theory, and how our culture’s ambivalent responses to death can figure in the life of the author
Development and validation of novel gold nanorod-based fluorescent nanoprobes intended for ex vivo cancer diagnosis
No full textMarketised forensic DNA-profiling in England & Wales
Get PDFPreviously held under moratorium from 20 March 2020 until 20 March 2022Forensic science provision in the United Kingdom has undergone significant, though uneven, development during the past decade. In England and Wales, forensic expertise is now delivered by way of a commercial market, whilst similar provision in Scotland, and Northern Ireland, remains within the public sector. As a result of marketisation, police forces (and other forensic ‘customers’) have become increasingly concerned with measuring economic value, whilst forensic science providers have been required to maintain an efficient, high-quality service that conforms to the overarching regulations. Early studies suggest that these structural, and regulatory, developments have had a marked impact upon the field of forensic DNA analysis, and may affect the way in which expert DNA evidence is constructed. This empirical research project seeks to assess the impact that these public policy, and organizational, developments, have had on the perspectives of forensic DNA-profiling experts. The project focuses on the perceived links between governance structures and the performance of forensic expertise, through the construction of analytical, and evaluative, reports. The study also considers the reported impacts of overarching regulatory incursions. The purpose of this unique study is to gain a clearer understanding of the ways in which forensic DNA profilers have responded to policy-driven structural changes, and to assess the perceived effects of resulting adaptations. The project has uncovered valuable data, demonstrating that respondents regard DNA reporting and evaluation in relation to serious crime as conforming to the highest scientific standards. However, the ways in which ‘volume’ crime cases are perceived to have been dealt with may raise more pressing questions. Indeed, certain trends are identified within the respondent’s testimony, based upon their experiences of the forensic market, which may raise concerns. Particular developments (such as the perception of case fragmentation and de-skilling, and concerns relating to the production of streamlined reports) could - if accurate - impact on the quality of expert opinion, and may potentially subvert the courts’ ability to arrive at sound determinations on questions of fact.Forensic science provision in the United Kingdom has undergone significant, though uneven, development during the past decade. In England and Wales, forensic expertise is now delivered by way of a commercial market, whilst similar provision in Scotland, and Northern Ireland, remains within the public sector. As a result of marketisation, police forces (and other forensic ‘customers’) have become increasingly concerned with measuring economic value, whilst forensic science providers have been required to maintain an efficient, high-quality service that conforms to the overarching regulations. Early studies suggest that these structural, and regulatory, developments have had a marked impact upon the field of forensic DNA analysis, and may affect the way in which expert DNA evidence is constructed. This empirical research project seeks to assess the impact that these public policy, and organizational, developments, have had on the perspectives of forensic DNA-profiling experts. The project focuses on the perceived links between governance structures and the performance of forensic expertise, through the construction of analytical, and evaluative, reports. The study also considers the reported impacts of overarching regulatory incursions. The purpose of this unique study is to gain a clearer understanding of the ways in which forensic DNA profilers have responded to policy-driven structural changes, and to assess the perceived effects of resulting adaptations. The project has uncovered valuable data, demonstrating that respondents regard DNA reporting and evaluation in relation to serious crime as conforming to the highest scientific standards. However, the ways in which ‘volume’ crime cases are perceived to have been dealt with may raise more pressing questions. Indeed, certain trends are identified within the respondent’s testimony, based upon their experiences of the forensic market, which may raise concerns. Particular developments (such as the perception of case fragmentation and de-skilling, and concerns relating to the production of streamlined reports) could - if accurate - impact on the quality of expert opinion, and may potentially subvert the courts’ ability to arrive at sound determinations on questions of fact
A SHM-based decision support system for risk management of bridge scour
No full textFlood-induced scour, the erosion of material around bridge foundations due to flowing water ,is by far the leading cause of bridge failures worldwide. Although recent developments in sensor technology have resulted in more structures being monitored, practical applications of scour monitoring systems are limited. Thus, there is a need of quantifying the benefits stemming from the use of Structural Health Monitoring (SHM) systems for bridge scour assessment and of methodologies supporting the decision-making process of transport agencies responsible for scour risk management with information from scour sensors.;This thesis presents a probabilistic framework and a Decision Support System (DSS) for scour risk management of road and railways bridges, aiming to extend current procedures by incorporating (i) the various sources of uncertainty characterising the scour estimation, and (ii) information from scour sensors. The probabilistic framework for the estimation of bridge scour depth is based on a Bayesian network approach that exploits information from scour sensors to achieve a more precise estimate of the scour depth at unmonitored bridges. The DSS for bridge scour management is an SHM- and event-based decision model producing measurement-informed scour thresholds triggering bridge closure to traffic under heavy floods.;The functioning of the DSS is illustrated by considering as case study a network of road bridges crossing the same river in Scotland, under a heavy flood scenario. Only one of these bridges is instrumented with a scour monitoring system. The probabilistic framework demonstrates that the limited data from the scour sensors allow a significant reduction of uncertainty in the scour estimates at unmonitored bridge piers. This reduction is in the order of 70%, leading to a more precise classification of the bridge scour risk and to an increase of about 10% of the scour thresholds that trigger bridge closures compared to the ones chosen by transport agencies in their decision plans.Flood-induced scour, the erosion of material around bridge foundations due to flowing water ,is by far the leading cause of bridge failures worldwide. Although recent developments in sensor technology have resulted in more structures being monitored, practical applications of scour monitoring systems are limited. Thus, there is a need of quantifying the benefits stemming from the use of Structural Health Monitoring (SHM) systems for bridge scour assessment and of methodologies supporting the decision-making process of transport agencies responsible for scour risk management with information from scour sensors.;This thesis presents a probabilistic framework and a Decision Support System (DSS) for scour risk management of road and railways bridges, aiming to extend current procedures by incorporating (i) the various sources of uncertainty characterising the scour estimation, and (ii) information from scour sensors. The probabilistic framework for the estimation of bridge scour depth is based on a Bayesian network approach that exploits information from scour sensors to achieve a more precise estimate of the scour depth at unmonitored bridges. The DSS for bridge scour management is an SHM- and event-based decision model producing measurement-informed scour thresholds triggering bridge closure to traffic under heavy floods.;The functioning of the DSS is illustrated by considering as case study a network of road bridges crossing the same river in Scotland, under a heavy flood scenario. Only one of these bridges is instrumented with a scour monitoring system. The probabilistic framework demonstrates that the limited data from the scour sensors allow a significant reduction of uncertainty in the scour estimates at unmonitored bridge piers. This reduction is in the order of 70%, leading to a more precise classification of the bridge scour risk and to an increase of about 10% of the scour thresholds that trigger bridge closures compared to the ones chosen by transport agencies in their decision plans
Formulation of targeted drug-loaded nanoparticles for lung cancer therapy
Get PDFThe use of combination chemotherapy for treatment of lung cancer has been proven to be more effective than single-agent therapy. Such combination, when used in conjunction with nanoparticle carriers has the potential to effectively deliver the therapeutic payload to the cancer sites with minimal side effects. Small scale production method of liposome in laboratory setting such as thin film hydration requires post-processing steps to achieve desired physical characteristics and upscaling such method would prove to be economically unfeasible. Laboratory scale liposome purification methods such as dialysis and ultracentrifugation also suffer from similar limitation in upscaling. These challenges need to be overcame to streamline liposome production from laboratory to commercial scale whilst maintaining the desired liposome characteristics.;In this study, liposomal formulations with varying molarratio of 1, 2-Distearoyl-sn-glycero-3-phosphocholine, 1, 2-Dipalmitoyl-sn-glycero-3-phosphocholine, 1, 2-Distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) and cholesterol were fabricated using microfluidics technique with staggered herringbone mixer. Desired liposomal formulations were obtained by manipulating fabrication characteristics such as total flow rate (TFR) and aqueous-to-lipid flow rate ratio. Selected stable liposomal formulations were then subjected to entrapment of cisplatin and irinotecan, filter centrifugation and tangential flow filtration (TFF) methods, scaleup fabrication process, entrapment efficiency and release studies, lyophilisation and invitro assay against A549 cells. It was also observed that these stable liposome formulations are suitable for entrapment of both cisplatin and irinotecan and demonstrated higher cytotoxicity against A549 cancer cells in comparison with their free drug counterparts.;TFF method was found to be more effective in purification and concentrating large volume of liposomal suspension. Scaling up fabrication volume exhibited no significant impact on the physical characteristics, entrapment efficiencyand entrapped material release characteristics of the liposomes. The results of this study demonstrated the feasibility, scalability and modularity of dual-loaded irinotecan and cisplatin in a liposomal system and also its higher efficacy against A549 cancer cells, paving the way for the use of this liposomal system for lung cancer therapy.The use of combination chemotherapy for treatment of lung cancer has been proven to be more effective than single-agent therapy. Such combination, when used in conjunction with nanoparticle carriers has the potential to effectively deliver the therapeutic payload to the cancer sites with minimal side effects. Small scale production method of liposome in laboratory setting such as thin film hydration requires post-processing steps to achieve desired physical characteristics and upscaling such method would prove to be economically unfeasible. Laboratory scale liposome purification methods such as dialysis and ultracentrifugation also suffer from similar limitation in upscaling. These challenges need to be overcame to streamline liposome production from laboratory to commercial scale whilst maintaining the desired liposome characteristics.;In this study, liposomal formulations with varying molarratio of 1, 2-Distearoyl-sn-glycero-3-phosphocholine, 1, 2-Dipalmitoyl-sn-glycero-3-phosphocholine, 1, 2-Distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) and cholesterol were fabricated using microfluidics technique with staggered herringbone mixer. Desired liposomal formulations were obtained by manipulating fabrication characteristics such as total flow rate (TFR) and aqueous-to-lipid flow rate ratio. Selected stable liposomal formulations were then subjected to entrapment of cisplatin and irinotecan, filter centrifugation and tangential flow filtration (TFF) methods, scaleup fabrication process, entrapment efficiency and release studies, lyophilisation and invitro assay against A549 cells. It was also observed that these stable liposome formulations are suitable for entrapment of both cisplatin and irinotecan and demonstrated higher cytotoxicity against A549 cancer cells in comparison with their free drug counterparts.;TFF method was found to be more effective in purification and concentrating large volume of liposomal suspension. Scaling up fabrication volume exhibited no significant impact on the physical characteristics, entrapment efficiencyand entrapped material release characteristics of the liposomes. The results of this study demonstrated the feasibility, scalability and modularity of dual-loaded irinotecan and cisplatin in a liposomal system and also its higher efficacy against A549 cancer cells, paving the way for the use of this liposomal system for lung cancer therapy
Peridynamics theory and its applications in isotropic and functionally graded beam and plate structures
Get PDFIn recent two decades, as an alternative formulation to Classical Continuum Mechanics (CCM), peridynamics (PD) has been rapidly progressed for solid mechanics applications. Instead of expressing equations of motion in partial differential equation form as in CCM, PD equations of motion are expressed in integro-differential equation form. Moreover, PD equations do not contain any spatial derivatives, which offer certain advantages especially for the solution of problems including displacement discontinuities due to the existence of cracks. This thesis emphasizes the introduction of governing equations for currently popular beam and plate models in peridynamics framework. The formulations are derived by using Euler-Lagrange equation and Taylor series expansion and verified by considering benchmark problems with comparison against finite element analysis results. In addition, the implementation of peridynamic beam and plate formulations in finite element framework is explained. Moreover, the classical peridynamic formulations (bond based, ordinary state based and non-ordinary state based) are revisited.In recent two decades, as an alternative formulation to Classical Continuum Mechanics (CCM), peridynamics (PD) has been rapidly progressed for solid mechanics applications. Instead of expressing equations of motion in partial differential equation form as in CCM, PD equations of motion are expressed in integro-differential equation form. Moreover, PD equations do not contain any spatial derivatives, which offer certain advantages especially for the solution of problems including displacement discontinuities due to the existence of cracks. This thesis emphasizes the introduction of governing equations for currently popular beam and plate models in peridynamics framework. The formulations are derived by using Euler-Lagrange equation and Taylor series expansion and verified by considering benchmark problems with comparison against finite element analysis results. In addition, the implementation of peridynamic beam and plate formulations in finite element framework is explained. Moreover, the classical peridynamic formulations (bond based, ordinary state based and non-ordinary state based) are revisited
Understanding the pharmacological consequence of functional P2Y1- P2Y12 heterodimerisation
No full textG protein-coupled receptors (GPCRs) are a superfamily of transmembrane proteins that are responsible for transducing extracellular stimuli into intracellular responses. GPCRs are essential to a wide variety of distinct pathophysiologies and behaviours and represent approximately 34% of FDA-approved, human drug targets. In recent years the classical concept that GPCRs are monomeric membrane receptors has been challenged by a growing number of reports indicating that they can form dimers and higher-order functional oligomers. Furthermore, this has been demonstrated to affect receptor trafficking, ligand sensitivity, desensitization, and downstream effector response. Thus, an understanding of GPCR oligomerisation is vital to understand receptor dynamics. The P2Y1 and P2Y12 receptors belong to the class A family of GPCRs and are widely expressed throughout the body. There is growing evidence that purinergic receptors also exist as oligomers. Previously, the Kennedy lab proposed the formation of a constitutive heterodimer between coexpressed human P2Y1 and P2Y12 receptors, based on functional responses. Evidence of a physical interaction between the two receptor subtypes was, however, lacking. The aim of this project was, therefore, to use a variety of experimental techniques to determine if P2Y1 and P2Y12 receptors interact physically to form dimers and how this affected receptor function. In this study, tSA201 cells were transfected with hP2Y1 and hP2Y12 receptors containing a haemagglutinin (HA) or fluorescent protein (FP) tag. Transfection efficiency was first optimised for all receptor constructs and experimental conditions. Fluorescence microscopy then showed that both receptors localised at the cell plasma membrane and in close proximity to each other. By quantification the receptors on the cell surface, it is found that P2Y1 receptors expressed more on the cell surface in compare to P2Y12 receptors. Interestingly, hP2Y12 receptor surface expression decreased when coexpressed with the hP2Y1 receptor. The hP2Y1 and hP2Y12 receptor agonist, ADP, induced internalisation of both receptors when they were expressed on their own, but not when they were coexpressed. Physical interaction between hP2Y1 and hP2Y12 receptors was investigated using co-immunoprecipitation (co-IP), proximity ligation assay (PLA) and fluorescence lifetime imaging microscopy Förster resonance energy transfer (FLIM-FRET). These experiments demonstrated that P2Y1 and P2Y12 receptors formed a dimer that localised to the cell plasma membrane and the distance between both receptors decreases with AR-C69931MX addition. Moreover, in this study, the P2Y1-P2Y12 dimer was found natively in BV-2 microglial cells. Also, AR-C69931MX demolished the calcium induced by ADP in BV-2 cells, which is a similar finding noticed by Kennedy lab but in there combinant system. These findings reveal P2Y1 and P2Y12 receptor heterodimerisation with implications upon receptor internalisation and signalling in recombinant and endogenous receptor cell models. The next step requires further understanding of how these events might influence the pharmacology of both receptors and their function in normal physiology and disease.G protein-coupled receptors (GPCRs) are a superfamily of transmembrane proteins that are responsible for transducing extracellular stimuli into intracellular responses. GPCRs are essential to a wide variety of distinct pathophysiologies and behaviours and represent approximately 34% of FDA-approved, human drug targets. In recent years the classical concept that GPCRs are monomeric membrane receptors has been challenged by a growing number of reports indicating that they can form dimers and higher-order functional oligomers. Furthermore, this has been demonstrated to affect receptor trafficking, ligand sensitivity, desensitization, and downstream effector response. Thus, an understanding of GPCR oligomerisation is vital to understand receptor dynamics. The P2Y1 and P2Y12 receptors belong to the class A family of GPCRs and are widely expressed throughout the body. There is growing evidence that purinergic receptors also exist as oligomers. Previously, the Kennedy lab proposed the formation of a constitutive heterodimer between coexpressed human P2Y1 and P2Y12 receptors, based on functional responses. Evidence of a physical interaction between the two receptor subtypes was, however, lacking. The aim of this project was, therefore, to use a variety of experimental techniques to determine if P2Y1 and P2Y12 receptors interact physically to form dimers and how this affected receptor function. In this study, tSA201 cells were transfected with hP2Y1 and hP2Y12 receptors containing a haemagglutinin (HA) or fluorescent protein (FP) tag. Transfection efficiency was first optimised for all receptor constructs and experimental conditions. Fluorescence microscopy then showed that both receptors localised at the cell plasma membrane and in close proximity to each other. By quantification the receptors on the cell surface, it is found that P2Y1 receptors expressed more on the cell surface in compare to P2Y12 receptors. Interestingly, hP2Y12 receptor surface expression decreased when coexpressed with the hP2Y1 receptor. The hP2Y1 and hP2Y12 receptor agonist, ADP, induced internalisation of both receptors when they were expressed on their own, but not when they were coexpressed. Physical interaction between hP2Y1 and hP2Y12 receptors was investigated using co-immunoprecipitation (co-IP), proximity ligation assay (PLA) and fluorescence lifetime imaging microscopy Förster resonance energy transfer (FLIM-FRET). These experiments demonstrated that P2Y1 and P2Y12 receptors formed a dimer that localised to the cell plasma membrane and the distance between both receptors decreases with AR-C69931MX addition. Moreover, in this study, the P2Y1-P2Y12 dimer was found natively in BV-2 microglial cells. Also, AR-C69931MX demolished the calcium induced by ADP in BV-2 cells, which is a similar finding noticed by Kennedy lab but in there combinant system. These findings reveal P2Y1 and P2Y12 receptor heterodimerisation with implications upon receptor internalisation and signalling in recombinant and endogenous receptor cell models. The next step requires further understanding of how these events might influence the pharmacology of both receptors and their function in normal physiology and disease
Novel energy-optimal solutions to the inverse kinematics problem of redundant manipulators
Get PDFRobotic manipulators are today used in many industrial and field applications, especially in the kinematically redundant ones, which offer the possibility to approach a specific end-effector pose in infinitive different ways. This freedom allows to optimise secondary task alongside the main goal to drive the end-effector through a specific trajectory, and such optimisation problem has motivated the work of many researchers in the last decades. Historically, the energy of the manipulator has been considered a particularly important optimisation cost function: it is relevant in industrial settings, where manipulators operations are a standing cost, and even more in field environments, such as space, where the available power is limited.;This thesis presents a study about inverse kinematics algorithms for redundant manipulators, aimed at optimising the energy required to perform manipulation tasks. First, a literature review surveying inverse kinematics and optimisation for both fixed-base and free-floating manipulators is presented. This presents the state of the art in the field and illustrates the motivation for this thesis. It also outlines the main challenges encountered in the development of optimisation algorithms for redundant manipulators.;After this, two algorithms are presented and discussed within the thesis, a global and a local one. Both are based on nonlinear optimisation techniques. The global problem is talked first, and a method is proposed that can optimise different cost functions related to either kinetic energy or torques, with linear and nonlinear constraints, such as torque, power, and periodic motion. Furthermore, the algorithm is able to individuate multiple optima when they are present, thus increasing the chances to find the best (global) optimum.;A local algorithm based on prediction of kinetic energy integral has also been developed. In order to illustrate related challenges, a workspace analysis is first presented that illustrates difficulties in providing reliable prediction of kinetic energy values along a specific end effector trajectory. Kinematic indexes are discussed through a qualitative and quantitative analysis aimed at assessing their correlation with kinetic energy, and results of a canonical correlation analysis is presented. Furthermore, it is illustrated that the a spaceborne robotic manipulator can be controlled concurrently with the Attitude and Orbit Control Systems of spacecraft, adding extra degrees of freedom.;Following this, a local algorithm based on a predictive estimation of kinetic energy integral along a specified trajectory is presented and discussed. This algorithm is based on a simplified optimisation problem that allows to assess the direction of motion that will cause the smallest increase in the kinetic energy integral. This produces solutions that are closer to the global optimum respect to traditional algorithms.;Simulations with a 3-DoF planar robot are used to validate the results. The global method is validated against a global algorithm existing in literature and shown to be able to solve a wider class of problems. The local algorithm is statistically compared against existing inverse kinematics methods, showing a reduction in kinetic energy up to 30%. The thesis is completed by a discussion about limits and further improvements of the work hereby presented.Robotic manipulators are today used in many industrial and field applications, especially in the kinematically redundant ones, which offer the possibility to approach a specific end-effector pose in infinitive different ways. This freedom allows to optimise secondary task alongside the main goal to drive the end-effector through a specific trajectory, and such optimisation problem has motivated the work of many researchers in the last decades. Historically, the energy of the manipulator has been considered a particularly important optimisation cost function: it is relevant in industrial settings, where manipulators operations are a standing cost, and even more in field environments, such as space, where the available power is limited.;This thesis presents a study about inverse kinematics algorithms for redundant manipulators, aimed at optimising the energy required to perform manipulation tasks. First, a literature review surveying inverse kinematics and optimisation for both fixed-base and free-floating manipulators is presented. This presents the state of the art in the field and illustrates the motivation for this thesis. It also outlines the main challenges encountered in the development of optimisation algorithms for redundant manipulators.;After this, two algorithms are presented and discussed within the thesis, a global and a local one. Both are based on nonlinear optimisation techniques. The global problem is talked first, and a method is proposed that can optimise different cost functions related to either kinetic energy or torques, with linear and nonlinear constraints, such as torque, power, and periodic motion. Furthermore, the algorithm is able to individuate multiple optima when they are present, thus increasing the chances to find the best (global) optimum.;A local algorithm based on prediction of kinetic energy integral has also been developed. In order to illustrate related challenges, a workspace analysis is first presented that illustrates difficulties in providing reliable prediction of kinetic energy values along a specific end effector trajectory. Kinematic indexes are discussed through a qualitative and quantitative analysis aimed at assessing their correlation with kinetic energy, and results of a canonical correlation analysis is presented. Furthermore, it is illustrated that the a spaceborne robotic manipulator can be controlled concurrently with the Attitude and Orbit Control Systems of spacecraft, adding extra degrees of freedom.;Following this, a local algorithm based on a predictive estimation of kinetic energy integral along a specified trajectory is presented and discussed. This algorithm is based on a simplified optimisation problem that allows to assess the direction of motion that will cause the smallest increase in the kinetic energy integral. This produces solutions that are closer to the global optimum respect to traditional algorithms.;Simulations with a 3-DoF planar robot are used to validate the results. The global method is validated against a global algorithm existing in literature and shown to be able to solve a wider class of problems. The local algorithm is statistically compared against existing inverse kinematics methods, showing a reduction in kinetic energy up to 30%. The thesis is completed by a discussion about limits and further improvements of the work hereby presented
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