Complex models for genetic sequence data

PhD ThesisIn this thesis, the aim is to develop biologically motivated Bayesian models in two areas: molecular phylogenetics and time-series metagenomics. In molecular phylogenetics, the goal is generally to learn about the evolutionary history of a collection of species using molecular sequence data, for example, DNA. Evolutionary history is represented graphically using evolutionary trees, where the root of a tree represents the most recent common ancestor of all species in the tree. Substitutions in sequences are modelled through a continuous time Markov process, characterised by an instantaneous rate matrix, which standard models assume is stationary and time-reversible. These assumptions are biologically questionable and induce a likelihood function which is invariant to a tree’s root position. This is detrimental to inference, since a tree’s biological interpretation depends on where it is rooted. By relaxing both assumptions, we introduce two new models whose likelihoods can distinguish between rooted trees. These models are non-stationary, with step changes in the rate matrix on each branch. Each rate matrix belongs to a non-reversible family of Lie Markov models, which are closed under matrix multiplication. The two models differ in that a different non-reversible Lie Markov model is used in each. We perform our analysis in the Bayesian framework using Markov chain Monte Carlo methods. We assess the performance of our models using a simulation study, before considering an application to a Drosophila data set, where most models fail to identify a plausible root position. In time-series metagenomics, counts of operational taxonomic units (OTUs), which are pragmatic proxies for microbial species, are modelled over time. We have weekly counts of different OTUs from two tanks in a wastewater treatment plant. We develop a Bayesian hierarchical vector autoregressive model to model the dynamics of the OTUs, whilst also incorporating environmental and chemical data. Clustering methods are explored to reduce the dimensionality of our data and mitigate the issue of large proportions of zero-counts in the data. We use a seasonal phase-based clustering approach and a symmetric, circulant, tri-diagonal error structure. The autoregressive coefficient matrix is assumed to be sparse, so we explore different priors that allow for sparsity by analysing simulated data sets before selecting the regularised horseshoe prior for our hierarchical model. The chemical and environmental covariates are incorporated through a time varying mean. Finally, we fit the model to the data from each tank using Hamiltonian Monte Carlo

Using atomic force microscopy to analyse the geomechanical properties of organic rich rocks

PhD ThesisClimate change will have a major impact on society in the 21st century and beyond, unless the right measures are taken in the next decade. These measures require a drastic decrease in carbon dioxide emissions to reduce the concentrations of CO2 in the atmosphere most likely through sequestration into geologic formations. Organic matter has a key role in two major types of carbon sequestration play; as a key component of a shale seal in many conventional reservoirs, and comprising the majority of coal reservoirs. As such recent research has focused on the mechanical properties of this organic component, with the Atomic Force Microscope and Nanoindentation used to measure Young’s modulus at the nanoscale. This research is expand upon by investigating the trends in organic matter Young’s modulus within marine shales, and compare an immature marine shale (Tarfaya) to a lacustrine equivalent (Green River) using the AFM. The results of this study indicate that there is a clear trend of marine shales exhibiting a bimodal distribution in modulus, with a soft phase centered around 5-9GPa and a stiffer phase centered around 18-24GPa. 13C NMR spectroscopy indicates that the increase in stiffness is tied to an increase in aromatic carbon, which could indicate increases in modulus across all organic matter with maturity. Here AFM is used on a suite of coal macerals from different depositional environments and maturities to assess if there are common trends. The results of this highlight that the modulus distribution of coal macerals is generally unimodal, and softer than that in shales, with all modal values <10GPa. There is however, a similar trend in terms of a stiffening with maturity, with all macerals stiffer in the mature Northumberland Coal than in the immature cannel or paper coals. Thermal modelling suggests that differential strain is more likely in immature coals, where there is a greater difference moduli of liptinite and inertinite macerals. This problem is reduced in the mature coal, with little difference between the maceral moduli, suggesting that deeper mature coal seams are better targets for CCUS than shallower less mature seams. Machine learning can be used to maximise already collected data by making inferences on samples where information is limited, using the trends from a larger dataset. Here the first attempt at using machine learning on SEM, EDX and AFM data is documented, using data collected from the Eagle Ford and Green River shales, with the goal of making mineralogic and geomechanical predictions. A variety of supervised and unsupervised machine learning methods were used, including; Multi-Layer Perceptron, KNN and Random Forest. The accuracies of these models on the test/training data is generally above 85%, and in the case of the KNN and Random Forest above 95%. However, when the model are used on an unrelated dataset, the accuracy decreases significantly. This research indicates that if machine learning is to be used, the training dataset and model should be selected with the end result in mind, whilst acquiring the datasets using a similar technique to a similar quality.NERC Centre for Doctoral Training Oil and Gas scheme and Newcastle University

Understanding international postgraduate students’ adjustment in a British university: motivations for study abroad and subsequent academic, sociocultural and psychological experiences

Ph. D. Thesis.The rapid growth of international student mobility has become an increasingly important feature of the higher education landscape in recent decades (Yu and Moskal, 2019). With the continually growing population of students studying abroad, the subsequent adjustment experiences are receiving greater research attention (Wang, 2018). Therefore, following a growing trend in the UK research context (Young et al., 2013, Schartner and Young, 2016, Yu and Moskal, 2019), this longitudinal study investigated the adjustment process of full-time taught MA Degree postgraduate international students from the humanities and social sciences at a single British university. The focus was on their motivations for study abroad and subsequent academic, socio-cultural, and psychological adjustment. A mixed-methods research design was adopted, combing qualitative interviews and quantitative questionnaire surveys. The qualitative phrase aimed to identify students’ academic, socio-cultural, and psychological adjustment trajectories over time. The questionnaires were introduced as a complement to measure some specific issues, including perceived benefits of studying abroad, difficulties and relevant coping strategies, friendship, and social contacts (N=120, 108 and 102). Both interviews (N=16) and questionnaire surveys (N=120,108, and 102) were conducted in three stages across a nine-month period: The beginning of students’ programs of study (October 2018), the beginning of their second semester (February 2019), and the end of their taught period (June 2019). The findings indicated that adjustment is a complex process affected by many factors, and ‘success’ in all three domains’ was closely related to the help from co-nationals. The data revealed that the perceived value of the overseas study, personal or family-related reasons, and financial issues were deemed the main factors motivating students to pursue overseas study. The students themselves tended to focus more on academic rather than socio-cultural and psychological adjustment. Therefore, they felt more satisfied with their academic experiences. In the sociocultural domain, due to the issues such as personal agency or perceived cultural distance, international students usually lacked contact with host students. In terms of psychological adjustment, it was found that most of the students had a positive experience, although it was affected by their academic performance at times. Overall, the research data did not support the ‘U-curve’ hypothesis of adjustment. Various internal or external factors, individual attitudes, and expectations affected the adjustment directly or indirectly. This research provides theoretical and empirical knowledge on the adjustment of international students in the UK and fills an existing gap in cross-cultural perspectives. This research approach can be adopted in studies within other research contexts, especially in other global Western universities. In practical terms, it increases current knowledge or potentially enriches the quality of support international students when they study in the U

Foreign direct investment location and tax incentive policy in Indonesia

PhD ThesisForeign Direct Investment (FDI) has become a ‘mantra’ for developing countries, as not only is it a source of capital to boost economic development, but an important source of employment and technology. Many developing countries provide incentives to attract foreign investors, such as preferential taxes, but the evidence for these is mixed. Some find they are important, but others that they do not affect FDI location. Indonesia is of interest, since it is a large and rapidly developing Asian economy, which has pursued a policy of ‘openness’ towards FDI. This is supported by a programme of taxes and other incentives, but despite using these measures for more than fifty years their effect is uncertain, and they remain controversial. The purpose of this thesis is to analyse the characteristics of FDI location in Indonesia and to explore the role of tax and other incentives. Overall, the thesis makes three main contributions. First, it provides an up-to-date analysis of FDI location in Indonesia using an original dataset and covering the ‘New Order’ period from the mid-1990s. Second, it undertakes a large-scale questionnaire survey of foreign-owned plants in Indonesia to establish their nature and motive for location. Third, the thesis carries out face-to-face interviews with Indonesian policymakers at a high-level to explore the rationale for inward investment and tax incentive policies. Inward FDI to Indonesia has grown steadily over the last decade, and it is now about US$20 billion per annum. This represents about 2.1% of Indonesian GDP, while comparable domestic investment is about two-thirds smaller, indicating its importance. Making use of realization data provided by the Indonesian Investment Coordinating Board, the thesis shows that the vast majority of FDI in Indonesia is located on Java, the most populous region, and reflects market and labour resource-seeking. Regions outside Java are important more recently and are a target for FDI in mining and agriculture, especially from Europe and America. However, most FDI is from Asia, especially Singapore and Japan. The manufacturing share of FDI has increased over time, although the mean project size is smaller. The thesis finds a sharp division between the Special Areas, in which the incentives are applied intensively, as FDI seeks labour resources and exports, whereas outside these areas it supplies the domestic market. The survey shows that tax incentives are not the main factor for influencing investors’ decisions to locate in Indonesia. Thus, while investors include these incentives in their appraisal, they tend not to be the critical factor for investment in Indonesia. This seems to be well-perceived xvi by policymakers, so that political economy considerations are important for the continuance of these incentives. Other developing countries offer these incentives, so that the expectation of investors and policymakers is that these subsidies will also be available in Indonesia. Further, the tax incentives have largely evaded scrutiny, and the location of FDI has been attributed to other factors. Finally, by being seen to ‘do something’ to attract FDI in a fairly minimal way, the tax incentives are a means by which the government garners political support.The government of Indonesia, which sponsored my PhD study through the Indonesia Endowment Fund for Education (LPDP

Microbiology of Indonesian extremobiospheres : from unexplored actinobacteria diversity to novel antimicrobial discovery

PhD ThesisThis present study addresses the need to extend bioprospecting campaigns to neglected and untapped biomes with the expectation that they will contain novel actinobacteria able to synthesise new bioactive compounds. Culture-dependent and culture-independent methods were used to establish the extent and biotechnological potential of actinobacteria in environmental samples drawn from thirteen extreme biomes located in the Indonesian archipelago. Nearly all of the environmental samples contained small numbers of actinobacteria which formed varying fractions of bacteria growing on the selective media. Over one hundred representative isolates were assigned to 8 orders, 15 families and 21 genera based on 16S rRNA gene sequence data. Almost 74% of these isolates inhibited the growth of wild type strains in standard plug assays., 19 filamentous isolates from the primary screens inhibited cell envelope, cell wall, DNA, fatty acid and RNA synthesis in secondary screens based on Bacillus subtilis reporter strains. Nineteen isolates with interesting bioactivity profiles or representing rare taxa were assigned to one new genus, 10 novel species and 2 new subspecies following extensive genome-based polyphasic studies. Several of these “key” isolates belonged to novel amycelial and filamentous actinobacteria rarely isolated from extremobiospheres. The metagenomic analyses of composite environmental samples from the extreme habitats contained an extraordinary degree of previously unknown actinobacterial diversity. The richest source of uncultivated actinobacterial taxa accounted for 4 new orders, 10 novel families, 30 new genera and 5790 undiscovered species was from the Parangkusumo sand-dune sample. Rank abundancy curves showed that nearly all of the actinobacterial diversity detected in this and the other composite samples from extreme habitats represented low abundancy taxa. These results demonstrate that extreme Indonesian habitats are an enormous untapped source of novel actinobacteria that present unique opportunities for bioprospecting of potential drug leads at a time when multidrug resistant pathogens are an ever-increasing threat to global health.Indonesian Endowment Fund for Education (LPDP)

Cyanobacterial biocomposites for in situ treatment of domestic wastewater

Ph. D. Thesis.Centralised water treatment infrastructure is increasingly being put under strain due to population growth. In situ treatment (i.e. a distributed treatment network) may minimise or even negate the need for centralised infrastructure. Cyanobacteria grown in open-ponds and photobioreactors are used for wastewater treatment; however these cultivation systems struggle with batch consistency and have a high capital cost. Biocomposites (biomass immobilised on a solid substrate within a semi-porous matrix) theoretically support increased active biomass within a more compact space and prevent cell wash-out, thereby increasing bioremediation efficiency. Wild-type Synechococcus elongatus (strains PCC 7942 and CCAP 1479/1A) and a novel engineered strain (SBG363; designed to overproduce and excrete sucrose) were trialled as potential bioremediation biocomposites. Commercial latex-based binders (AURO 320 and 321) were used for biocoatings formulation, and applied to a selection of natural and synthetic textiles to form textile-based biocomposites. Biomass growth was increased by up to 800%, retaining up to 97% of biomass after 72 hours. Sucrose output from S. elongatus SGB363 was unaffected. Wild-type immobilised biomass supported up to 80% greater CO2 sequestration over a 20-day period than its suspension culture control. However, after three and six days of immobilisation there were no significant differences in total protein content, CO2 removal, or orthophosphate uptake per cell between immobilised and suspension treatments. Whole transcriptome sequencing (RNA-Seq) was attempted to determine the genetic response of S. elongatus surviving within a biocoating. However, immobilised samples had very low RNA integrity number equivalents that prevented differential gene expression analysis. This research shows that cyanobacteria textile biocomposites are a promising solution for process intensification in the wastewater treatment industry, and addresses concerns regarding environmental safeguarding. Metabolically active biocomposites can be used for de-centralised wastewater treatment applications thereby alleviating problems associated with Victorian era infrastructure without creating an additional environmental burden.Enviresearch Foundatio

The impact of urban form and shading on microclimate and indoor air temperatures of dwellings: a case study of Erbil, Kurdistan, Iraq

PhD ThesisThe history of the Kurdistan region of northern Iraq is complex, however it was established as an autonomous region (Kurdistan‐Iraq) in 1991, since when it has flourished in stark contrast to the remainder of Iraq and Syria. The capital of Kurdistan is the historic city of Erbil one of the most ancient cities in the world (with at least 4000 years of history). In recent times, the city has expanded dramatically after 2003, in a series of concentric rings around the central ancient Citadel, to accommodate Kurds from both Kurdistan‐Iraq and the returning diaspora. This rapid urban expansion has turned its back on the traditional design principles of the ancient Citadel which was designed to work in harmony with the hot dry climate; organic designs of narrow, winding streets designed around the needs of the pedestrian. Instead this organic morphology has been replaced by grid‐iron planning, with street widths designed to accommodate motor vehicles. The alignment of these grid‐iron street patterns has been driven by geometry rather than referencing urban micro climatic needs. The main aim of this research is to investigate the impact of urban form and shading on the urban micro climate and the indoor air temperature of dwellings in the new (post 2003) developments of Erbil. To achieve these aims two methods were used: The prediction of the urban micro climate used ENVImet, a numerical climate simulation program. The indoor air temperatures were predicted using the building energy simulation software IES Virtual Environments (IES‐VE). The climate modelling compared traditional and grid‐iron morphologies and demonstrated that the traditional morphology produced lower external air temperatures. For the modern grid‐iron morphologies, higher wind speeds in the urban canyons were achieved when the prevailing wind from the South West flowed through a canyon grid aligned North‐South and East‐West. Shading by both trees and wire mesh was modelled. Both reduce the external mean radiant temperature, but have little impact on the external air temperature. Moreover, the wire mesh shading did not reduce the urban wind speeds, but the tree shading did reduce urban wind speeds. When shading buildings, the reduction in indoor air temperature was small; whilst the shading mesh reduced solar gain it also reduced night‐time losses to the clear night sky, yielding a small reduction in indoor air temperature. However, when purposeful night‐time ventilation was modelled, the reduction in indoor air temperature was significant. By combining building shading (reducing solar gain) and night time purpose ventilation (increasing nigh‐time cooling) allows greater freedom in façade design. This permits modern house design to have a similar thermal performance to the traditional house design. The study has developed a novel method to simulate efficiently wire mesh shading both for urban micro climates and buildings. It has shown how the modern grid‐iron urban morphology can be adapted to provide improved micro climates and how individual houses can be designed to benefit from these changed micro climates. For the future, it is recommended that full scale testing of whole housing shading be undertaken and how this shading can be adapted to reflect the local identity of the region

Mechanisms of moral responsibilities: Designing and deploying digital technologies for perpetrators of domestic violence

PhD ThesisWhere prevention and intervention resources should be focused to mitigate domestic violence is an important topic within academic policy and practice. While there are a range of digital tools available to support victim-survivors subject to domestic violence, no tools have been designed to challenge the abusive and harmful behaviours of perpetrators. In this thesis, I explore the experience of how existing and novel technologies used in the context of perpetrator interventions in the third sector within the United Kingdom are being leveraged to rebalance the over-responsibility society bestows on victim-survivors, along with the under-responsibility we ascribe to perpetrators. I accomplish this through developing a conceptual framework that seeks to promote spaces for design and further intervention capable of assisting such organisations in holding perpetrators responsible for their abusive behaviours and facilitating their journey of behaviour and attitude change towards non-violence. Through this work, I conceptualise the compelling moral responsibilities intrinsic to interactions with technological systems between perpetrators and support workers, which I elicit through a focused ethnography. I highlight four spaces of negotiation concerning a person’s responsibility for changing their abusive behaviour, which I refer to as ‘mechanisms’ to convey their fundamental and interconnected nature: self-awareness, acknowledging the extent of harms, providing peer support, and being accountable to demonstrate change. To further investigate these spaces for negotiation, I conducted three studies to understand the contextual dependencies of design that focuses on the responsibility of domestic violence perpetrators through: (1) the development of an interactive storytelling system to promote learning about agency and perspective-taking, (2) the design of a smartphone application to support crisis management and the prevention of physical violence, and (3) the design, deployment and evaluation of an asynchronous peer support process between two groups of perpetrators. The outcomes of this conceptual and empirical inquiry are manifold. First, I provide a detailed account of how responsibility is explored in practice between support workers and perpetrators to suggest design considerations for future systems in this context. Secondly, I provide a conceptual framework to aid researchers and designers in better navigating designing for responsibilities for violent behaviours, and outline implications for how this might be achieved. Finally, I offer a methodological and ethical ii considerations which outlines ways in which support workers and perpetrators can be actively included within the co-design of digital tools while mitigating the elevation of risk. These contributions aim to fundamentally reimagine the roles and possibilities for digital tools within domestic violence, looking beyond today’s victim-focused and security-oriented paradigms to propose a more transformative orientation focused on preventing the harm done by perpetrators

Spatial modelling of transcription dynamics in bacterial gene regulatory networks

Ph. D. Thesis.In Synthetic biology, researchers can alter the DNA sequence of organisms such that the behaviour to specific inputs is predictable. Regulatory systems have been ‘hacked’ into doing computation, help with bio-production, aid in personalised medicine and providing highly specific sensors. A major bottleneck in current synthetic biology is that models fail to predict system behaviour reliably, causing recent progress to be reliant on the trial and error of model-assisted system designs. One of the reasons for the models to fail is the neglect of Spatial effects. While this neglect simplifies models, recent experimental data shows localised effects. This work shows that only the combination of 3D cytosol diffusion and the 1D sliding along the chromosome of transcription factors can explain localised effects; the modelling transcription factors initial sliding route after formation reproduces experimental results. However, one essential assumption for the model described above is the initial location of a functional transcription factor at the encoding gene. While the coupled transcription and translation in prokaryotes are experimentally verified and can lead to the localisation of Transcription Factor proteins, this localisation must be assumed to be transferred to the active dimer form to reproduce the experiment. To substantiate this assumption, this work expands the limited field of protein dimerisation. A new model is introduced to explain the localisation effect with an extra pathway we call Translation Mediated Dimerisation. Here, the partially formed transcription factors still undergoing translation are thought to meet and form a dimer while still constrained to the mRNA on the other end. Even if this occurs in a minority of events, this can drastically affect non-linear behaviour. This model allows utilisation of localised effects for the rational design of system dynamics otherwise unavailable, expanding the possibilities and increasing the efficiency of synthetic biolog

A Multimodal Critical Discourse Analysis of Entrepreneurship in Entre-tainment

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)