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

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    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)

    Elucidating the molecular drivers of prostate development using iPSC-derived organoids

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    PhD ThesisProstate cancer (PCa) is one of the leading causes of death among men in developed countries. Advances in uncovering the mechanisms of this disease have in part been hampered by the absence of a suitable human model that incorporates the complexity and variability of the disease. Inherent limitations of current models have prevented a complete understanding of PCa. Recently, patient-derived prostate organoids have emerged as an additional tool to complement current models. However, the process of prostate organoid generation using primary tissue can be inefficient. To overcome this and other limitations of current prostate organoid methodologies, our group developed an alternative method to produce prostate organoids using induced pluripotent stem cells (iPSCs). However, the process of prostate differentiation is complex and has yet to be fully elucidated. This research focused on optimizing the in vitro conditions of iPSC differentiation to prostate organoids, with a focus on using neonatal seminal vesicle mesenchyme (SVM) to induce prostate specification. The optimal culture conditions to produce prostate organoids were established and methods to maintain and analyse organoids were standardized. Organoids generated were composed of luminal, basal, and stromal cells, with rare neuroendocrine and stem cells. Additionally, we sought to elucidate the molecular drivers of prostate induction through RNA-sequencing analyses of the early rat prostate and inductive SVM. We were able to uncover candidate genes enriched in the inductive mesenchyme that may be involved with prostate specification. We were also able to identify genes and pathways in the epithelium that are likely responsible for responding to cues from the mesenchyme, leading to prostate differentiation. The candidates found in this research can be evaluated for their ability to improve iPSCs to prostate differentiation, which may eliminate the need for rodent mesenchymal tissue in this model. Furthermore, the datasets generated in this research can be further interrogated to better understand the reactivation of developmental genes in adulthood, leading to PCa

    A fault-tolerant triple three phase induction machine

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    PhD ThesisThis thesis focuses on the development of a fault tolerant induction motor which is capable of continued operation with winding and power converter short-circuits. The motor takes advantage of a segmented stator to function under extreme circumstance. When splitting a motor stator into separate segments of power, there is still coupling between segments, which is minimised by partitioning the motor into a series of circumferentially separated arcs. In this way, each segment of the stator is electrically, thermally, physically independent and each arc can be viewed as a linear motor; however, it has been found that the motor cannot be functional as a normal motor at all speeds. The reason of that phenomenon will be studied and concluded to be the large asynchronous space harmonics produced by each arc, which prevents the system from functioning successfully. According to the reason, a modified rotor is introduced which overcomes this problem and allows operation with not only open circuit, but also in short circuits for what is believed to be the first tim

    Bayesian optimal design using stochastic gradient optimisation and surrogate utility functions

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    PhD ThesisExperimental design is becoming increasingly important to many applications from genetic research to robotics. It provides a structured way of allocating resources in an e cient manner prior to an experiment being conducted. Assuming a model for the data, one approach is to introduce a utility function to quantify the worth of a design given some data and parameters. Typically experiment-speci c utility functions are di cult to elicit and hence a pragmatic choice of utility concerning the information gained about the model parameters is used. Bayesian experimental design aims to maximise the expected utility accounting for uncertainty in the model parameters and the data which could be observed. For this approach, di culties arise as the expected utility is typically intractable and computationally costly to approximate. Modern applications often seek high dimensional designs. In these settings existing algorithms such as the MCMC scheme of Müller (1999) and ACE (Overstall and Woods, 2017), require a high number of utility evaluations before they converge. For the most commonly used utility functions this becomes a computationally costly exercise. Therefore there is a need for an e cient and scalable method for nding the Bayesian optimal design. The contributions of this thesis are as follows. Firstly, stochastic gradient optimisation, a scalable method widely used in the eld of machine learning, is applied to the Bayesian experimental design problem. The second contribution is to consider a utility function based on the Fisher information matrix as a Bayesian utility function by showing it has a decision theoretic justi cation. These utilities are often available in a closed-form so are fast to compute. The nal contribution is to investigate surrogate functions for expensive utilities as an e cient way of nding promising regions of the design space

    Innovative techniques for deployment of microservices in cloud-edge environment

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    PhD ThesisThe evolution of microservice architecture allows complex applications to be structured into independent modular components (microservices) making them easier to develop and manage. Complemented with containers, microservices can be deployed across any cloud and edge environment. Although containerized microservices are getting popular in industry, less research is available specially in the area of performance characterization and optimized deployment of microservices. Depending on the application type (e.g. web, streaming) and the provided functionalities (e.g. ltering, encryption/decryption, storage), microservices are heterogeneous with speci c functional and Quality of Service (QoS) requirements. Further, cloud and edge environments are also complex with a huge number of cloud providers and edge devices along with their host con gurations. Due to these complexities, nding a suitable deployment solution for microservices becomes challenging. To handle the deployment of microservices in cloud and edge environments, this thesis presents multilateral research towards microservice performance characterization, run-time evaluation and system orchestration. Considering a variety of applications, numerous algorithms and policies have been proposed, implemented and prototyped. The main contributions of this thesis are given below: Characterizes the performance of containerized microservices considering various types of interference in the cloud environment. Proposes and models an orchestrator, SDBO for benchmarking simple webapplication microservices in a multi-cloud environment. SDBO is validated using an e-commerce test web-application. Proposes and models an advanced orchestrator, GeoBench for the deployment of complex web-application microservices in a multi-cloud environment. GeoBench is validated using a geo-distributed test web-application. - i - Proposes and models a run-time deployment framework for distributed streaming application microservices in a hybrid cloud-edge environment. The model is validated using a real-world healthcare analytics use case for human activity recognition.

    Transitioning power distribution grid into nanostructured ecosystem : prosumer-centric sovereignty

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    PhD ThesisGrowing acceptance for in-house Distributed Energy Resource (DER) installations at lowvoltage level have gained much significance in recent years due to electricity market liberalisations and opportunities in reduced energy billings through personalised utilisation management for targeted business model. In consequence, modelling of passive customers’ electric power system are progressively transitioned into Prosumer-based settings where presidency for Transactive Energy (TE) system framework is favoured. It amplifies Prosumers’ commitments into annexing TE values during market participations and optimised energy management to earn larger rebates and incentives from TE programs. However, when dealing with mass Behind-The-Meter DER administrations, Utility foresee managerial challenges when dealing with distribution network analysis, planning, protection, and power quality security based on Prosumers’ flexibility in optimising their energy needs. This dissertation contributes prepositions into modelling Distributed Energy Resources Management System (DERMS) as an aggregator designed for Prosumer-centered cooperation, interoperating TE control and coordination as key parameters to market for both optimised energy trading and ancillary services in a Community setting. However, Prosumers are primarily driven to create a profitable business model when modelling their DERMS aggregator. Greedy-optimisation exploitations are negative concerns when decisions made resulted in detrimental-uncoordinated outcomes on Demand-Side Response (DSR) and capacity market engagements. This calls for policy decision makers to contract safe (i.e. cooperative yet competitive tendency) business models for Prosumers to maximise TE values while enhancing network’s power quality metrics and reliability performances. Firstly, digitalisation and nanostructuring of distribution network is suggested to identify Prosumer as a sole energy citizen while extending bilateral trading between Prosumer-to- Prosumer (PtP) with the involvements of other grid operators−TE system. Modelling of Nanogrid environment for DER integrations and establishment of local area network infrastructure for IoT security (i.e. personal computing solutions and data protection) are committed for communal engagements in a decentralise setting. Secondly, a multi-layered Distributed Control Framework (DCF) is proposed using Microsoft Azure cloud-edge platform that cascades energy actors into respective layers of TE control and coordination. Furthermore, modelling of flexi-edge computing architecture is proposed, comprising of Contract-Oriented Sensor-based Application Platform (COSAP) employing Multi-Agent System (MAS) to enhance data-sharing privacy and contract coalition agreements during PtP engagements. Lastly, the Agents of MAS are programmed with cooperative yet competitive intelligences attributed to Reinforcement Learning (RL) and Neural Networks (NN) algorithms to solve multimodal socio-economical and uncertainty problems that corresponded to Prosumers’ dynamic energy priorities within the TE framework. To verify the DERMS aggregator operations, three business models were proposed (i.e. greedy-profit margin, collegial-peak demand, reserved-standalone) to analyse comparative technical/physical and economic/social dimensions. Results showed that the proposed TE-valued DERMS aggregator provides participation versatility in the electricity market that enables competitive edginess when utilising Behind-The-Meter DERs in view of Prosumer’s asset scheduling, bidding strategy, and corroborative ancillary services. Performance metrics were evaluated on both domestic and industrial NG environments against IEEE Standard 2030.7-2017 & 2030.8-2018 compliances to ensure deployment practicability. Subsequently, proposed in-house protection system for DER installation serves as an add-on monitoring service which can be incorporated into existing Advance Distribution Management System (ADMS) for Distribution Service Operator (DSO) and field engineers use, ADMS aggregator. It provides early fault detections and isolation processes from allowing fault current to propagate upstream causing cascading power quality issues across the feeder line. In addition, ADMS aggregator also serves as islanding indicator that distinguishes Nanogrid’s islanding state from unintentional or intentional operations. Therefore, a Overcurrent Current Relay (OCR) is proposed using Fuzzy Logic (FL) algorithm to detect, profile, and provide decisional isolation processes using specified OCRs. Moreover, the proposed expert knowledge in FL is programmed to detect fault crises despite insufficient fault current level contributed by DER (i.e. solar PV system) which conventional OCR fails to trigger

    The breadth of open innovation activities : antecedents and outcomes, a dynamic capability perspective

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    PhD ThesisBuilding on the theory of dynamic capabilities, this study seeks to examine the implementation of open innovation at the firm level. Specifically, this research focuses on the breadth of open activities, a potential first-order dynamic capability to examine its antecedents and outcomes. It examined (a) the effect of the breadth of open innovation activities (e.g., external technology acquisition, crowdsourcing, customer co-creation in R&D projects) as a potential first-order dynamic capability, on firm innovativeness. Additionally, this research studied (b) the effect of a potential second-order routine, representing open innovation training, and potential second-order dynamic capabilities including social information systems capabilities, the anticipation of new technologies, and relational capability on the breadth of open innovation activities. A pilot test of six semi-structured interviews was conducted to revise the conceptual model of this study. Then, online surveys, as the main method of data collection used in this research, were distributed mainly to innovation and R&D managers at high value manufacturing companies in the UK. 211 completed surveys, representing a satisfactory response rate of 21.1%, were obtained and used in the hierarchical regression method adopted to analyse the data in this study. This research found that the breadth of open innovation activities is a first-order dynamic capability resulting in a higher level of firm innovativeness, but only up to certain extent, after which lower firm innovativeness results. Open innovation training, social information systems capabilities and relational capability were found to be key antecedents supporting the breadth of open innovation activities. This study contributed to the inbound open innovation implementation literature at the firm level, in relation to antecedents and outcomes of the breadth of open innovation activities, through the dynamic capabilities theory. It also provided better guidance for managers in this regard, and suggested future research areas

    Constraining Models of Collective Motion in Biological Systems

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    PhD ThesisAnimals moving together as one is a commonly seen spectacle in both the sky, with flocks of birds, and in the oceans, with school of fish. Mathematical models have been developed over the last 50 years to gain a deeper understanding into how such coordination occurs or to recreate the behaviour digitally. There has been extensive numerical simulation and analysis done for these models but little comparison to actual data. This is due to the complexity of obtaining high quality data suitable for analysis. We were able take advantage of lightweight high definition cameras and drone technology to collect footage of collective behaviours. In this thesis we describe a computer vision algorithm we devised to detect and track individual sheep in the drone footage we collected. The algorithm emphasises the differences in the colours of the sheep and the grass background in order to locate the sheep. It then tracks the individuals throughout the video. In total the trajectories of 45 or more sheep were extracted from 14 videos ranging from 150 frames to 593 frames. In some of these videos the quadbike and farmers herding the sheep were also tracked. From these trajectories we were able to extract quantities such as average speed and global alignment which can then be used to compare to simulated data. We describe a number of models from the literature which aim to reproduce the types of behaviours we observed in our sheep flocks and some of these we expand on to make them include new features such as allowing agents speeds to change or allow agents to interact with a predator whist in an enclosed area. We go on to compare our observational data to two different types of these models. The first of these was a family of models which were able to replicate the emergent flocking behaviour seen in some of the observations. The second was a model able to simulate data to compare to our observations of “steady-state” flocking as well as being able to include the movement of the quadbike or farmer herding the animals. We will compare our observational data to simulated data using an approximate Bayesian computation rejection scheme to calculate an approximate joint posterior distribution for the parameters in each of the models. The parameters of these models were sampled from a Latin hypercube meaning we are able to cover the full parameter space efficiently

    The role of visual arts participation in promoting children’s social and emotional wellbeing

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    Ph. D. Thesis.This thesis explores the potential role of visual arts (VA) participation in promoting children’s social and emotional wellbeing (SEW). It contains three chapters: a systematic literature review (SLR); a bridging document which explains the rationale and methodology for an empirical study in the light of the findings from the SLR; and an empirical study. In recent years, there has been a greater emphasis on how schools may support children’s SEW. The need for this has increased over the course of this research due to the ongoing COVID-19 pandemic, and the potential challenges children have experienced throughout. Wider literature, the SLR and empirical study in this thesis suggest a potential role of VA participation, as an accessible, inclusive and universal approach to promoting SEW for all children. The aim of the SLR is to investigate the outcomes of VA interventions for children’s social and emotional wellbeing. A thematic synthesis was conducted to analyse five studies with mixed methods data. Findings suggest that in a group context, VA participation may have a positive impact on children’s social and emotional skills, confidence and self-esteem, relationships and connectedness. They may contribute to a sense of autonomy, positive affect and relaxation. However, evidence is limited and there are mixed results from quantitative data. A need is identified for research into universal art-based approaches which promote SEW for all children, which is outlined in the bridging document. The bridging document also discusses philosophical, methodological and ethical considerations which informed the empirical study. The aim of the empirical study is to understand the potential role of a universal choice-based VA approach for children’s SEW, from the views and experiences of a primary school class. The study involved an action research type design to implement a choice-based VA approach with a Year 3 class, over a period of six weeks. Following this, qualitative data was gathered from small groups of children and the teacher, which was analysed using thematic analysis. Findings suggest that in a whole class context, choice-based VA participation may provide a space for playful exploration, emotional expression and regulation within a class community. Findings are discussed in relation to children’s SEW, along with possible implications for schools and educational psychologists

    Reactive coupling for biodiesel production with integrated glycerol valorisation

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    Ph. D. Thesis.The increasing production of biodiesel globally over the last 20 years has increased the supply of “crude” glycerol. Initially, glycerol was a valuable by-product but is now low value or a waste product, due to mismatch between supply and demand. Valorisation of glycerol is an obvious route to improving the process economics. In this work, we investigated glycerols in situ valorisation by conversion to various oligomers (used in the pharmaceutical, food, and cosmetics industries) and glycerol ethers (used as oxygenated compounds to improve fuel combustion in Diesel engines). This is an example of "reactive coupling", a technique in which the by-product of one reaction is simultaneously converted to an added value product in a second reaction (in a single "pot"), thereby reducing the number of process steps. The main objective for this work is to produce glycerol free biodiesel with reduced methanol usage and fast triglyceride conversion using reactive coupling as a novel technique. This work will for the first time demonstrate the production of biodiesel and glycerol ethers in a single pot. This aimed to reduce glycerol byproduct and methanol recycling. First, the study the convert glycerol in a stainless steel reactor. Reactive coupling was then performed to convert triglyceride with simultaneous conversion of the glycerol to added value products. Sulfuric acid was used as catalyst for the reaction, as it is compatible with all the desired reactions. It is also cheap and can tolerate triglyceride with high FFA levels during biodiesel production. High temperature in transesterification results in fast conversion of triglyceride. The catalyst and temperatures used are suitable for both biodiesel reaction and glycerol etherification. Highest conversion of glycerol achieved was 68%, with over 90% selectivity to diglycerol in 5h. To avoid producing undesired by-products (such as acrolein) and higher oligomers (such as pentaglycerol), the recommended conditions are 3 wt% catalyst concentration, and a temperature of less than 150 oC. Furthermore, a kinetic model was fitted to the experimental data with activation energy of 112 kJmol-1 and pre-exponential factor of 2.18x1011 L.mol-1s-1. The thermodynamic analysis showed the reaction to be endothermic, less disordered, and non-spontaneous with an enthalpy (ΔH) 109 kJmol-1, entropy (ΔS) – 38.1 Jmol-1K-1, and Gibbs free energy (G) 125 kJmol-1 respectively. Reactive coupling achieved complete conversion of triglycerides and 100% FAME yield in 1h. About 60% of the glycerol was converted in parallel, with approximately 90% selectivity to glycerol ether and 10% to diglycerol. A temperature of not more than 150 oC is sufficient for this process with 3 wt% catalyst concentration and molar ratio 4:1 – 6:1. Some of the benefits of the reactively coupled process vs conventional processing are the rapid separation of the biodiesel phase from the glycerol phase, low alcohol to oil ratios, and the production of value-added products from the crude glycerol. The model should make scale-up of this process more predictable and robust. Combined reactive extraction and reactive coupling were also studied, i.e., reactive coupling on the oilseeds, rather than the oil. Over 90% of biodiesel production was achieved and complete conversion of the glycerol to glycerol ether and polyglycerol. However, a substantially higher molar ratio of methanol to oil (400:1) was required, likely to be uneconomic. There were various non-triglyceride products in the extract, which would probably necessitate extra downstream processing. In summary, for the first time, this work demonstrates reactive coupling to produce biodiesel, polyglycerol, and glycerol ether production using sulfuric acid as catalyst. The main advantages of this technique were: i. Reduced glycerol by-product by up to 60%. ii. Reduced methanol usage, from 20:1 to 4:1 – 6:1. This will remove/reduce downstream processing. iii. Rapid conversion of triglyceride. iv. Easy/fast separation of glycerol phase from FAME phase. Furthermore, this study demonstrated proof-of-concept for combined reactive extraction and reactive coupling. Hence, oil in seeds can be converted directly to biodiesel, glycerol, and added-value products. This study’s success shows that the glycerol by-product can be converted to a useful product directly during biodiesel production. Potentially, this will reduce waste generation and diversify the market of biodiesel producers.Petroleum Technology Development Fund (PTDF), Nigeri

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