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    Modelling the dynamics of the upper ocean in the Eastern Tropical Pacific and its interactions with the tropical atmosphere

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    Ph. D. Thesis.The physical behaviour of the central and eastern tropical Pacific regions is characterized by a complex variety of multi-scale interacting processes. The Madden-Julian Oscillation (MJO) is the primary mode of intraseasonal variability in the tropical atmosphere. Although convection, together with related cloudiness and precipitation, tends to dissipate east of the 180º meridian, the MJO wind signal continues to progress eastward across the eastern Pacific and South America and into the tropical Atlantic. This research explores numerically the response of the upper ocean in the central and eastern tropical Pacific regions to MJO forcing. We use a global, intermediate resolution configuration of the Nucleus for European Modelling of the Ocean (NEMO) framework version 3.6, referred to as ORCA1-LIM3, forced with daily atmospheric forcing from the Coordinated Oceanic Reference Experiments (CORE) dataset version 2, for the period 1990 to 2000. The results show a strong influence of the MJO on temperature, salinity, zonal currents, and vertical currents in the first 300 m of depth, particularly at the equator. The intraseasonal wind is the key forcing factor that modulates the impact of the MJO. This is except for the temperatures at the mixed layer depth, the halocline, and the pycnocline, in the regions of the Central American Pacific coast and the southwestern Mexican coast where the influence of the MJO can be observed even in the absence of intraseasonal wind forcing. The impact of the MJO on the ocean's internal intraseasonal variability is analysed in the case of tropical instability waves. We show that the barotropic and baroclinic conversion terms that control the eddy kinetic energy levels in the region vary in magnitude with the phases of the MJO. These results have ramifications for understanding ocean intraseasonal variability, which is a critical step towards improving our ability to make more reliable mid-range ocean weather and ocean climate forecasts for the region.Ministry of Science, Technology, and Communications of Costa Ric

    Alpha-synuclein post-translational modifications and abnormal network oscillations in Lewy body dementias

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    Ph. D. Thesis.Lewy body dementias (LBDs) are age related neurodegenerative diseases characterized by the presence of abnormal alpha-synuclein (αSyn) inclusions termed Lewy Bodies (LBs) and Lewy Neurites (LNs) and represent the second most common form of neurodegenerative dementia after Alzheimer’s disease. LBDs are progressive pathologic conditions with variable clinical signs and symptoms including dementia and abnormal neuronal network oscillations, with no currently available treatment. The interaction between αSyn post-translational modifications (PTMs) and neuronal dysfunction is a core concept in LBDs. Accumulating evidence shows that, αSyn PTMs, such as, phosphorylation, ubiquitination and nitration, are events that occur in the context of synucleinopathies. I hypothesised that these PTMs lead to the formation of toxic/aggregated forms of αSyn that causes neuronal dysfunctions/death and impair neuronal network oscillations. The aim of this thesis was to Identify the PTMs of αSyn, analyse their distribution in LBDs, correlate them with the distribution of parvalbumin expressing interneurons in in post-mortem brain tissues of LBD patients, and analyse its links with mitochondrial dysfunction and neuronal network impairments. Using, electrophysiological and immunohistochemical protocols in selected cases that fulfilled the neuropathological criteria for LBDs and control cases, sourced from Newcastle Brain Tissue Resource (NBTR), and Transgenic A30P and control C57BL6 mice from comparative biology centre (CBC), I found that aged A30P mice had greater sensitivity to the mitochondrial inhibition by reducing the area power of the gamma frequency oscillations. In addition, parvalbumin expressing cells are significantly altered in humans, specifically in areas associated with the development of prodromal stages of LBDs, these same areas correlated with regions that presented higher Burden of αSyn phosphorylation. In conclusion, this thesis demonstrates that, reduction in density of parvalbumin cells depicts the impairments in gamma frequency oscillations and correlates with an increase in αSyn PTMs in some regions of LBD patients

    On the empirical economics of income persistence and class identity in the UK

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    PhD ThesisSocioeconomic gradients in life outcomes are important political issues and a key area of research for many applied economists. This thesis – comprising three empirical chapters – represents the culmination of a process of research and investigation into the measurement of income persistence and the role of class identity in shaping behaviour and health in the UK. The first empirical chapter explores measures of intergenerational income persistence and their sensitivity to researcher decisions. Using data from the British Cohort Study, 810 estimates of intergenerational persistence are produced. The chapter is the first to estimate and report the entire profile of persistence estimates with precedent in the literature for a given dataset. Through a novel application of the techniques from meta-regression, the effects of each researcher decision are estimated. The results confirm the existence of errors-in-variables and lifecycle bias and show that seemingly innocuous changes to variable definitions can lead to large fluctuations in persistence estimates. Rank coefficients are found to be the least sensitive to researcher decisions and are thus preferred over elasticities or correlations for comparative purposes. The thesis progresses from measuring the intergenerational transmission of advantage, to the process of how socioeconomic gradients occur. Specifically, from a health economics perspective, how can we better understand differences in behaviours between socioeconomic groups? The thesis applies a range of econometric methods to provide the first evidence on the economic role of subjective class identity on smoking behaviour and the relationship between relative deprivation and health. The second empirical chapter focuses on subjective class identity and risky behaviour, as measured by smoking. Data from the British Household Panel Survey (BHPS) suggests around 1 in 3 people in the UK state that they belong to a social class. A range of Two Part Models is used to demonstrate behavioural differences between individuals with a class identity and those without class identities. Working class identity individuals are more likely to smoke and, those that do, consume more cigarettes than individuals with no class identity. These are the first empirical findings to show that associations exist between subjective class identity and health behaviours even after controlling for a host of socioeconomic characteristics. These findings are consistent with predictions from the identity economics framework, given the literature on class, smoking and stigma. iii The third empirical chapter again uses data from the BHPS, to examine whether class identity has differential effects on the relationship between relative deprivation and measures of health (self-assessed health and psychological well-being). Heterogeneity analyses allow the associations to differ across subjective class identity groups. In measuring relative deprivation, the reference groups - with which individuals compare themselves – are allowed to vary with class identity. For each sample, outcome, and reference group, OLS is used alongside models designed to control for unobservable heterogeneity. Once time constant unobserved differences are controlled for there is no evidence of self-assessed health or psychological health costs from relative deprivation for males. For females, there is a significant positive relationship between relative deprivation and psychological well-being. This effect is driven by working class women and hypothesised to be an aspiration effect, i.e. as incomes in the reference group increase, the subject anticipates that their income too will increase, improving well-being. Each empirical chapter focuses on an aspect of the central theme, socioeconomic gradients in life outcomes. The key contributions are on the measurement of income persistence and the role of subjective class identity on health behaviours and outcomes. The central implications are the importance of transparency in the reporting of income persistence estimates and the need for accurate comparisons. As well as the need to consider self-assessed class identity in studies of risky behaviour and health inequalities, as these may provide more insight into the effects of health interventions and the existence of hard-to-reach individuals. Throughout, results also differ across gender, highlighting the need to consider gender when targeting policy messages

    Expanding the scope of DNA compatible chemistry for the application within DNA encoded libraries

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    PhD ThesisThe discovery of potential lead like molecules is a crucial phase for any drug discovery program. Current methods to identify lead molecules are often resource intensive, often requiring millions of compounds to be screened in biological assays. Reducing the time and cost taken to generate, store and screen large compound libraries would have a positive impact on academia and small pharmaceutical companies. DNA encoded libraries (DELs) aim to improve upon this by screening an entire library in a single vessel against a target and utilising the DNA tag to identify potential inhibitors. Current methods of preparing DELs are limited to chemistry that is compatible with DNA. These chemical methods are often limited to simple chemical reactions, such as cross-couplings and amide bond formation, which are used combinatoriality to generate vast libraries. As analogous chemical reactions are used, current libraries are often populated with compounds with similar physical properties and have limited structural diversity. The reactions used to generate DELs are often low yielding, or are limited in substrate scope, further reducing the diversity of potential libraries. Development of new approaches with DEL synthesis will increase the ability to synthesise libraries with greater chemical diversity and improved physical property profiles. Products produced from the encoded transformation paradigm. A new paradigm termed “encoded transformations” was introduced. This technique involves encoding a specific chemical transformation of a reactive core molecule instead of coding the addition of a building block. This would lead to a potential library of compounds with reduced overall molecular weight and more lead-like physical properties. A common reactive 2-oxobetenamide core was used and several chemical transformations have been successfully employed. These chemical transformations were developed off-DNA and provide a means to prepare libraries with significant scaffold diversity using DNA compatible chemistry. Micellar solvents have been shown to improve normal phase organic chemical reactions. Applying this technique to on-DNA synthesis vastly improved the scope and diversity of the reactants used. Both amide couplings and Suzuki-Miyaura reactions were successfully optimised utilising micellar media as a solvent. Optimisation was carried out in both examples by factorial experimental design (FED), which revealed second order relationships between variables tested that would not likely be discovered using conventional techniques. Products produced from novel micellar promoted Suzuki-Miyaura and amide reactions. These novel reactions were used to synthesise a prototype 6x6 library, which was PCR amplified and sequenced proving that reactions in micellar media do not cause DNA damage. The reverse amide coupling was then used to create a 99,405-member library, including compounds designed to specifically target the SARs-CoV-2 main protease (Mpro) binding site, using an array of both covalent and non-covalent inhibitors.AstraZenec

    Real-Time QoS Monitoring and Anomaly Detection on Microservice-based Applications in Cloud-Edge Infrastructure

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    Ph. D. Thesis.Microservices have emerged as a new approach for developing and deploying cloud applications that require higher levels of agility, scale, and reliability. A microservicebased cloud application architecture advocates decomposition of monolithic application components into independent software components called \microservices". As the independent microservices can be developed, deployed, and updated independently of each other, it leads to complex run-time performance monitoring and management challenges. The deployment environment for microservices in multi-cloud environments is very complex as there are numerous components running in heterogeneous environments (VM/container) and communicating frequently with each other using REST-based/REST-less APIs. In some cases, multiple components can also be executed inside a VM/container making any failure or anomaly detection very complicated. It is necessary to monitor the performance variation of all the service components to detect any reason for failure. Microservice and container architecture allows to design loose-coupled services and run them in a lightweight runtime environment for more e cient scaling. Thus, containerbased microservice deployment is now the standard model for hosting cloud applications across industries. Despite the strongest scalability characteristic of this model which opens the doors for further optimizations in both application structure and performance, such characteristic adds an additional level of complexity to monitoring application performance. Performance monitoring system can lead to severe application outages if it is not able to successfully and quickly detecting failures and localizing their causes. Machine learning-based techniques have been applied to detect anomalies in microservice-based cloud-based applications. The existing research works used di erent tracking algorithms to search the root cause if anomaly observed behaviour. However, linking the observed failures of an application with their root causes by the use of these techniques is still an open research problem. Osmotic computing is a new IoT application programming paradigm that's driven by the signi cant increase in resource capacity/capability at the network edge, along with support for data transfer protocols that enable such resources to interact more seamlessly with cloud-based services. Much of the di culty in Quality of Service (QoS) and performance monitoring of IoT applications in an osmotic computing environment is due to the massive scale and heterogeneity (IoT + edge + cloud) of computing environments. To handle monitoring and anomaly detection of microservices in cloud and edge datacenters, this thesis presents multilateral research towards monitoring and anomaly detection on microservice-based applications performance in cloud-edge infrastructure. The key contributions of this thesis are as following: • It introduces a novel system, Multi-microservices Multi-virtualization Multicloud monitoring (M3 ) that provides a holistic approach to monitor the performance of microservice-based application stacks deployed across multiple cloud data centers. • A framework forMonitoring, Anomaly Detection and Localization System (MADLS) which utilizes a simpli ed approach that depends on commonly available metrics o ering a simpli ed deployment environment for the developer. • Developing a uni ed monitoring model for cloud-edge that provides an IoT application administrator with detailed QoS information related to microservices deployed across cloud and edge datacenters.Royal Embassy of Saudi Arabia Cultural Bureau in London, government of Saudi Arabi

    Understanding grit in an organisational context : the concept of grit and its role as a predictor of work-related stress and employee performance

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    PhD ThesisIn recent years, non-cognitive personality factors have received increasing attention due to studies that suggested that they could be highly important in employee selection and development processes. Substantial research and practical reasoning suggests that the ability to persevere and be passionate about one’s long-term goals despite challenges and setbacks is considered a key factor of success in today’s society. This thesis focuses on grit, a non-cognitive personality trait grit that has been defined as a combination of perseverance and passion for long term goals. Building on inconclusive preliminary results that indicated that grit might be a crucial factor for employee performance and the experience of work-related stress, this thesis reports on research that aimed to explore the applicability of grit in the workplace. The research used a cross-sectional research design and empirically tested the predictive validity of grit on individual performance and its relationship to PsyCap, resilience and work-related stress in a stratified sample of the UK government’s Companies House Basic Company Data. To provide a holistic insight into the impact of grit on job performance, the three dimensions of task performance, organisational citizenship behaviour and innovative performance were assessed. A survey method was applied to a cross sectional sample of 2089 employees to provide generalisable results across UK workers. The findings of this research suggest that despite issues in its current conceptualisation, grit is a distinctive construct compared to resilience and PsyCap and impacts individual outcomes in the organisational context. Furthermore, findings suggest that grit is a significant predictor of job performance and work-related stress across the research sample. The findings have significant implications for theory by showing that grit is a unique personality characteristic that could enhance current HRM processes to increase employee performance and reduce work-related stress

    New Heteronormativity: The Gay-Straight Tipping Point in Suicide Prevention Amongst Male University Students in the U.S.

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    Ed. D. Thesis.In the United States, suicide is the second leading cause of death amongst university students aged between 25 and 34, and the second leading cause of death overall for people aged between 15 and 34. Men die by suicide at four times the rate of women across all age groups, at roughly 20 deaths per 100,000 individuals. This has been the case since the 1950s and stubbornly persists; defying interventions and harm reduction efforts designed to contain it. While such figures and trends are reflected across much of the western world, the U.S. has a particular problem. Young men at university are at the epicentre of the crisis. Prevention efforts increasingly focus on identities and social lives, with research fractured along concepts of sexuality, masculinity, and social constructs. This thesis examines this multifactorial, social ecology, and adopts a phenomenological framework to understand the place of prevention in the social and private spheres of male students at U.S. university campuses. The study explored the lived experiences of 29 students and utilised interpretative phenomenological analysis. The study found considerable understanding of constructed and socio-political factors amongst the group, including how recent shifts in the U.S. government had contributed to societal views of young men. Despite this self-insight, wavering resilience, and a growing frustration with the failure of statutory systems and the government to intervene has led to stalled prevention efforts in many university contexts. Academic and public health models must, jointly, find new means to consider wider influencing arenas on suicidality, heteronormativity, masculinity, sports, politics, and their place in the higher education environment. Findings are of considerable importance to agencies related to, and working at the forefront of, suicide prevention efforts and the intersection of masculinities and suicidalities

    Probing the evolutions and proliferations of beatmaking styles in hip hop music

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    Ph. D. Thesis.This PhD thesis investigates how a multiplicity of distinct styles of hip hop beats have materialised since hip hop music’s initial emergence from New York City in the 1970s. From the outset, I assert that the beat, that is, the musical component that might be thought of as the ‘backing track’ of a hip hop record or live performance, should be considered just as fundamental as an MC’s vocals. I proceed to observe that while hip hop can be – and usually is – invoked to mean a single genre, examples of hip hop beats from disparate regions and periods can sound radically different from one another, exhibiting divergent sonic signatures and compositional approaches. My research seeks to discover and engage critically with the factors that have caused this stylistic diversity. A musicological inquiry that eschews the priorities and standardisations of European-derived musical sensibilities in favour of a meaningful regard for hip hop culture’s aesthetics and creative strategies is pursued as I analyse a selection of significant region-specific and period-specific beat styles, and subsequently, a combination of online ethnographic work and a creative practice element leads my survey on the present state of underground beatmaking practice. Drawing from theories and applications of dialectics, I find that the history of hip hop beats and beatmaking can be apprehended by scrutinising the relationship between underground musical movements and the agents of the capitalist culture industry, with these two conflicting sides effectively working in tandem to ensure hip hop’s continued position at the vanguard of modern popular music. Crucially, I suggest that hip hop beatmaking constitutes a truly revolutionary form of composition that exposes and explodes the latent potentials of music technologies, both established and novel.Northern Bridge AHRC Doctoral Training Partnershi

    Real-time monitoring and forecasting of time series in healthcare applications

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    Phd ThesisType II diabetes is an increasingly common disease, but one in which the effects suffered by patients, such as hyperglycaemia, can be improved through careful monitoring and control of the factors that influence blood glucose levels. Advances in the Internet of Things (IoT) have made monitoring a person’s glucose levels more accessible, in that a continuous glucose monitoring (CGM) device in the form of a small sensor can be used to regularly report glucose levels to a bluetooth device, without the need for human intervention. Modelling the data from CGM devices online allows for short-term forecasts to be made that can assist in making real-time decisions regarding interventions to improve future glucose levels, such as behavioural changes. Additional data to monitor how active a person is can easily be collected by wrist-worn accelerometer devices. As activity levels directly impact glucose levels, bivariate models between glucose and activity data aim to provide improved forecasts. State space models are fitted to glucose data and activity data using a Bayesian modelling framework. The posterior distributions of model parameters are learned via Markov chain Monte Carlo (MCMC) methods. High frequency (100 Hz), tri-axial accelerometer data are reported alongside glucose observations recorded at five minute intervals and are transformed into univariate activity summaries. Discrete-valued state space models, known as hidden Markov models (HMMs), are used to classify the observations from the different activity summaries into activity intensities. Normal and skew Normal withinstate distributions are explored to better fit the observed activity summaries, as well as fitting models to transformations of the summaries where possible to reduce the skewness in the data. Gaussian state space models, known as dynamic linear models (DLMs), are explored to describe glucose levels, incorporating seasonal and autoregressive (AR) components. The results from these models then provide the basis for bivariate models that incorporate known activity states. This additional information is included in the DLMs as a regression covariate, which is formed by a weighted sum of lagged activity zones. Models between glucose levels and lagged carbohydrate intake are also considered, to better understand the effects of activity and food on glucose levels. A second application area is considered as an example of improved predictive performance where an influential variable is known alongside the quantity of interest. The production levels of liquid natural gas (LNG) at a gas plant are modelled by a DLM, with a regression on atmospheric temperature. The models are fitted in a frequentist framework for simplicit

    A Multimodal Critical Discourse Analysis of Entrepreneurship in Entre-tainment

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    PhD ThesisOver the past decade entrepreneurship has featured heavily in spheres of entertainment such as television. The term “entre-tainment” (Down, 2010) has been coined to capture the merging of, entrepreneurship and entertainment (Swail et al, 2014). One form of “entre-tainment” that has become widespread through international and globalised replication by approximately forty different countries is the format of reality television programmes such as Dragons’ Den which was the first version of the series in the English language. This thesis critically unpacks (i) the discourses of entrepreneurship in popular culture surrounding this specific entre-tainment genre, and (ii) what these discourses do, through Multimodal Critical Discourse Analysis. Three datasets are analysed, which will be referred to as ‘Layers’. Layer 1 is the discourse within the episodes of three versions of the television show, which are (i) Dragons’ Den (UK), (ii) Shark Tank (USA) and (iii) Planting Seeds (Caribbean). Layer 2 surrounds media produced by the show that is external to the episodes aired, and Layer 3 focuses on content produced by others about the shows. Reviewing discourses across different Layers enhances the insight of the interdiscursivity of entrepreneurship as constructed across social, cultural, and institutional divides, as this research is not solely limited to the discourses confined within the television shows but expands to include those from and about the shows. Entre-tainment was found to legitimise a version of entrepreneurship that values wealth above all else. This was achieved by positioning the desire and attainment of extreme individual wealth as morally and socially acceptable, thus naturalising this ideology while obscuring alternative motivations and types of entrepreneurship. Entre-tainment was also found to give celebrity entrepreneurs the power to influence public opinion not only in areas of business, but also in areas of social life unrelated to business enterprise, such as academia, government policy, marriage, parenting, and managing personal finances. This work contributes to the area of critical entrepreneurship studies as it fills the gap for research concerned with the influence cultural representations have had on re-imagining the entrepreneur (e.g. Jones & Spicer, 2009)

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