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    Demulsification of water/crude oil emulsions using functionalised PolyHIPEs in an electrostatic field

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    Ph. D. ThesisIn petroleum manufacturing, during the crude oil extraction process, water-in-crude oil emulsions with high stability are obtained which are stabilised due to the presence of indigenous surface-active materials within crude oil. The removal of water from crude oil is critical in producing saleable product. It should be conducted at source with the aim to overcome the cost of pumping and the problems associated with the corrosion in pipes during transportation. Many separation technologies exist, e.g. gravity separators, coalescence separators, centrifugal separators, stripping columns and vacuum distillation systems, but most of these cannot remove tightly emulsified or dissolved water in addition to their high cost. Thus, chemical treatments are often required to separate water from these emulsions. Recently, sulphonated hydrophilic micro-porous polymers (named PolyHIPE Polymers) were used as an active membrane layer in a cross-flow microfiltration process to separate water from water-in-crude oil emulsions. However, this did not sufficiently separate water from w/o emulsions under steady state conditions. Therefore, an alternative method for using polyHIPE to achieve the same results has been developed in this project. This thesis focuses on the removal of water and surface-active components from high stability water-in–crude oil emulsions by using a novel combination of a highly porous polymeric material sorbent with an electrostatic separation field to further enhance the efficiency of the separation process. The results are compared to a conventional separation processes. Several micro-porous polyHIPEs (PHPs) with varying functionality have been produced and characterised. These PHP polymers were then utilised in water separation trials from emulsions of water-in-crude oil with high stability. A continuous demulsification process has been developed and tested on a model seawater-in-crude oil emulsion by utilising different PHPs in presence of an electric field. In order to use the optimum samples of the PHPs in the demulsification process, the PHP samples were characterized in terms of morphology, surface area, water uptake, pore size distribution, EDX, and FTIR analyses. Different flow rates of emulsions and various electric field strengths (applied voltages) were employed in this separation process to evaluate their effect on the separation efficiency. Furthermore, the spent PHP samples were reused in the demulsification process to evaluate the potential for sorbent recovery and the change in separation efficiency after reuse. This study succeeded in achieving its main objective namely the production of environmentally sustainable demulsifiers on a laboratory scale. A silane PHP ecofriendly demulsifier was synthesized with a relatively high surface area of 98 m2/g, high water adsorption as well as its ability to remove surface-active species from crude oil that cause emulsification of crude oil such as Mg, Na, Cl and Ca. Another goal was to study the demulsification mechanism by utilising various types of sorbents including standard sulphonated PHP, in situ sulphonated PHP, bindzil PHP and silane PHP to identify the best performance. This required the development of a continuous demulsification process to work at a high electric field strength without breakdown (ranging from 1-5 kV over a few centimetres) and different emulsion inlet flow rates (from 100 to 1500 ml/min). It was found that the best separation efficiency was 89% by using the silane PHP demulsifier at a flow rate of 100 ml/min and an applied voltage of 5 kV. This is comparable to the best results achieved by other methods including chemical demulsification. When reusing the spent silane PHP in the demulsification process under similar parameters, the separation efficiency was reduced to 71%. The final aim, to eliminate the need for larger demulsification equipment by developing a novel approach for the separation of emulsions under the combined impacts of demulsifier and electric technique, was therefore successfully achieved.Oil Ministry, Midland Refineries Company, Ministry of Higher Education and Science Researc

    Characterisation of Marine Gel Particles and Associated Bacterial Communities

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    PhD ThesisGel particles including biopolymers, microgels, transparent exoploymeric particles (TEP), and other classes of exopolymeric substances (EPS) are ubiquitous in the marine environment. Despite the different names for these gel particles in the literature they represent closely related materials and will be referred to simply as marine gel particles (MGPs). MGPs have a natural ability to aggregate, forming large particles of ‘marine snow’ that play an important role in the carbon flux to the ocean floor and the biogeochemical cycling of carbon in the sea. MGP aggregates are also a habitat for bacteria and their metabolic activities can affect the structure and dynamics of the MGPs. Extracellular DNA (eDNA) as an abundant element in the marine environment. eDNA is a key component in the structural integrity of some biofilms, and likewise could have similar effect on the structure of MGP aggregates. Hence, it is hypothesized here that extracellular DNA (eDNA) is present in MGPs as a result of bacterial growth and lysis. Therefore, the aim of this study was to investigate the presence of eDNA in MGPs. In addition, to characterise the bacterial community associated with MGPs and to examine their functional potential focusing on the occurrence of nuclease genes. A further aim was to investigate the production of deoxyribonuclease (DNase) by marine bacteria isolated from free living and attached bacteria. Seawater samples collected from the North Sea and filtered through a 100-μm sieve and a 0.4 μm polycarbonate filters to collect MGPs. eDNA occurrence was probed by bioimaging with cell-impermeant fluorescent DNA dyes YOYO-1 and TOTO-3. For the bacterial community structure and function analysis, MGPs were subjected to total DNA extraction and sequencing of the V4 region of the 16S rRNA gene using illumina MiSeq. Marine bacterial isolates were also investigated for DNase secretion on methyl green DNase test agar, with genome sequencing being carried out for the most productive DNase isolate. Results of the bioimaging analysis and quantification of the MGP composition demonstrated for the first time the presence of eDNA in MGPs. Proteobacteria dominated the bacterial community structure within MGPs, where Pseudoalteromonas and Vibrio were the most abundant genera. The bioinformatics based functional predictions of the bacterial community using KEGG analysis also affirmed the presence of numerous nuclease genes. The results from studies of isolated strains reported for the first time DNase secreting bacteria associated with MGPs in the North Sea. Additionally, there are 43 nuclease genes present in the genome of the prolific DNase producer Serratia marcescens. In conclusion, the co- occurrence of eDNA and DNases in the MGPs indicate important implications for understanding the dynamics and properties of MGP in the world’s oceans. This work can contribute to a further understanding of the role of the bacterial activities in MGPs formation, degradation and sedimentation processes.Culture Attaché, Oman Embassy in London and the Ministry of Higher Education in the Sultanate of Oma

    Investigating gene regulatory networks in aorti arch artery development

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    PhD ThesisDevelopmental defects to the heart and aortic arch arteries are a leading cause of morbidity and occur in 22q11 deletion syndrome (22q11DS) patients. Formation of the aortic arch arteries requires the remodelling of the pharyngeal arch arteries (PAA) which depends on regulated gene expression and the interaction of multiple tissues. TBX1 has been identified as a leading causative gene in 22q11DS, however, the wide spectrum of defects present in 22q11DS patients suggests that modifier genes may contribute to this phenotypic variation. Tbx1, Pax9 and Gbx2, all independently required for cardiovascular development, are co-expressed in the pharyngeal endoderm, a tissue that provides signalling cues during PAA morphogenesis. Tbx1 and Pax9 genetically interact and Gbx2 is downregulated in both Tbx1-null and Pax9-null mice. The aim of this project was to establish the Gbx2-null phenotype and investigate a potential interaction between Gbx2 and Pax9 in the pharyngeal endoderm during cardiovascular development. Gbx2-null mouse embryos presented with 4th PAA-derived defects, such as right aortic arch, as well as outflow tract defects. Pax9+/-;Gbx2+/- mice were crossed to study the interaction between these genes by generating embryos with complex genotypes. The presentation of cardiovascular defects in Pax9+/-;Gbx2+/- mice showed a strong genetic interaction. Likewise, Pax9 heterozygosity modified the Gbx2-null phenotype, both increasing the penetrance of defects and causing the presentation of additional abnormalities. Conditionally deleting Gbx2 from the endoderm concomitantly with the heterozygous deletion of Pax9 resulted in cardiovascular defects, highlighting the pharyngeal endoderm as a key tissue in PAA morphogenesis and remodelling. Mouse models were used to study a potential Tbx1-Pax9-Gbx2 genetic network in cardiovascular development. In vitro models were used to investigate the interaction of Tbx1 and Pax9 with the Gbx2 coding region. The data presented in this thesis suggests that a Tbx1-Pax9-Gbx2 genetic network exists within the pharyngeal endoderm to control PAA morphogenesis

    Beyond the question : an interactionist study of Q & A sequences in oral financial results presentations

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    PhD ThesisIn this PhD Thesis the researcher applies the method of 'Conversation Analysis' from the field of linguistics to a setting in financial reporting. Conversation Analysis, short CA, is a qualitative method for the systematic study of social interaction. The foundation of analysis are detailed transcripts that enable the researcher to examine how institutional roles are understood and acted out through talk, or "how institutions are talked into being". The data set contains of Q & A sessions held after interim and annual results presentations by six major British investment banks in 2015. All banks are listed at the London Stock Exchange, were part of the FTSE100 in 2014, and uploaded video or audio files of meetings and conference calls on financial results in form of webcasts. Overall more than 13 hours of interactions between financial analysts and the management of respective corporations have been recorded and analysed. The study aims to show how that financial analysts make an effort in demonstrating cooperation and social solidarity with management in public interactions, and it is argued that both the financial analyst’s and the management’s behaviour construct the setting as one that enforces transparency. The findings of the study are organised as follows: Firstly, it is analysed how financial analysts perform their role publicly, by examining how patterns in question design demonstrate knowledgeability and entitlement to further information. The second empirical chapter shows how analysts do “being sceptical” when phrasing initial questions, and especially when following up on an answer. This was found to be accomplished by interactants through adopting one of two roles: The “puzzled” analyst, or the “diagnosing analyst”. It is argued that financial analysts use contrast structures to demonstrate affiliation instead of explicitly challenging the management’s accounts. Lastly, a third empirical chapter is dedicated to laughter in this setting. Both analysts and management use laughter to mitigate socially risky actions, like managing speaking rights, withholding information, or when challenging the askability of a question, which results in the co-creation of information request denials

    Bayesian calibration of stochastic kinetic models using a Dirichlet process mixture of Gaussian processes

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    Ph. D. Thesis.Stochastic kinetic models (SKMs) are an effective way to model complex biochemical and cellular systems. They describe how a number of species in a system interact with one another through time. To infer the parameters of these models, a number of MCMC techniques exist but these can often be both computationally intensive and time consuming due to the constant need to simulate from the stochastic process at each iteration. When inferring parameters of quite large or complex models, these simulations can become unmanageable. To tackle this, emulators can be used to approximate SKM output, a popular choice being a Gaussian process, however these do not provide accurate descriptions of output with multiple modes. A SKM of particular interest which exhibits this behaviour is the Schl ogl system which describes an exchange of chemicals between two material baths. This system, under certain conditions, is bistable. This motivates the need to nd a exible emulator that can capture this bimodality. By using a Dirichlet process mixture of Gaussian processes we explain how this model has useful features such as the exibility to increase or decrease the number of components in the mixture throughout parameter space as necessary. We apply the model to training data for the Schl ogl system with the aim of inferring the rate constants that gave rise to some noisy data from the system. We also look at a further approximation using variational inference and nd that this gives signi cant gains in terms of e ciency.Engineering and Physical Sciences Research Counci

    Vowel adaptation in English loanwords in Thai

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    Ph. D. Thesis. (Integrated)The use of English loanwords in everyday conversations of native Thai speakers is prevalent since many English words have been introduced to the Thai lexicon over the past 200 years. The nativisation of English loanwords into Thai has been carefully investigated in the last three decades; however, previous studies of Thai loanword phonology have primarily focused on consonants and tone assignment. Phonological adjustments made to the vowels have been less well-studied. This thesis investigates the phonological adaptation of English loanwords in Thai, focusing on adaptation patterns of monophthongs and diphthongs, and strategies employed to resolve non-native syllable structures which are ill-formed in Thai. The study examines the phonological processes that are involved in the Thai adaptation of English vowels, investigates how the best match for non-native vowels is determined and explores the role of native phonology in vowel adaptation. The loan data examined in the study were mainly drawn from standard Thai dictionaries. The analysis is conducted within the framework of Optimality Theory (OT) to explore how the grammar of the borrowing language deals with non-native segments and syllable structures which are ill-formed in the native language. The OT analysis demonstrates that English vowels which are not in accord with markedness constraints cannot surface in Thai, and their best matches are determined on the basis of acoustic closeness together with the phonological structure of the borrowing language. It also reveals that different repair strategies for imperfect syllable structures in native words and loanwords result from distinct constraint rankings for native lexical items and foreign words. The adaptation patterns identified in the loan corpus appear to show, firstly, that the phonetic characteristics of source vowels which are contrastive in the borrowing language are faithfully preserved in their adapted form, giving rise to phonological perception; secondly that a range of factors including phonetic, phonological, and non-linguistic factors are involved in determining how English vowels are realised in Thai; and thirdly that orthography plays a role if adaptation is underdetermined by other factors.Office of the Higher Education Commission in Thailan

    Impact of mitochondrial alterations on prostrate cancer progression

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    PhD ThesisCancer metabolism is characterised by a ‘Warburg shift’ to aerobic glycolysis with decreased mitochondrial oxidative phosphorylation (OXPHOS), feasibly mediated by alterations in mitochondrial DNA (mtDNA). However, despite recent advances in our understanding of nuclear genomic alterations in prostate cancer, there remains a paucity of data evaluating the impact of mitochondrial alterations in prostate cancer progression. Therefore, using publicly available genomic datasets, the mitochondrial molecular landscape of aggressive prostate cancer was characterized. This revealed a spectrum of mtDNA mutations under clonal selection pressures, reduced mtDNA copy number, and a transcriptomic profile composed of reduced mitochondrial and increased nuclear OXPHOS gene expression. In order to assess the downstream impact of these alterations and aid clinical translation, I developed an automated assay to evaluate proteomic OXPHOS defects in archived prostate cancer tissue microarrays at the single cell level. Upon unpicking widespread multi-faceted heterogeneity in OXPHOS protein expression, patients with low complex I abundance and increased mitochondrial mass appeared to be at increased risk of all-cause mortality at 20- year follow-up. The prognostic value of both mitochondrial molecular alterations and proteomic OXPHOS defects was enriched in patients with PTEN-loss and TMPRSS2:ERG fusion. Given that mitochondrial alterations and prostate cancer risk features are also associated with advancing age, transgenic models were generated to elucidate the impact of age-related systemic mitochondrial dysfunction on PTEN-deficient prostate cancer progression. Despite early mortality due to accelerated age-related phenotypes, attenuated tumour progression was observed, suggesting a tumour suppressive effect of systemic mitochondrial dysfunction. In conclusion, mitochondrial alterations exert diverse systemic and local effects on prostate cancer progression. Leveraging mitochondrial tissue biomarkers and mitochondrial-targeted systemic therapies may provide a novel approach for identifying aggressive prostate cancer and suppressing progression to lethal disease

    Discovering the tumour suppressor function of hepatocyte NF-κB1

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    Ph. D. ThesisAberrant activation of the NF-κB signalling pathway is associated with the development of many cancers. We have previously demonstrated that global NFKB1 knock-out mice (Nfkb1-/-) develop spontaneous low-level chronic inflammation, liver disease and cancer as they age. In addition, when they are given the carcinogen diethylnitrosamine (DEN) to induce liver cancer they develop significantly more tumours and at an earlier stage. Nfkb1-/- mice present with defects in both the immune and the epithelial compartment, therefore it is not possible to dissect the cell-specific role of NFKB1 as a tumour suppressor. To determine the hepatocyte-specific tumour suppressor role of NFKB1, we have generated a novel hepatocyte-specific NFKB1 knock-out mouse (Nfkb1hep-/-). WT or Nfkb1hep-/- mice were subjected to different treatment regimens with either the hepatotoxin CCl4 or the carcinogen DEN to induce acute inflammation, fibrosis or hepatocellular carcinoma, to assess the role of hepatocyte NFKB1 in the progression from liver inflammation to cancer. In addition, acute CCl4 injury and chronic DEN injury experiments were conducted in AAV-TBG-CRE mice, whereby adenoviral deletion of hepatocyte NFKB1 was induced. Here we demonstrate that, while hepatocyte Nfkb1 showed a limited protective role in acute inflammation and fibrosis, mice lacking hepatocyte Nfkb1 displayed a significant increase in tumour number and grade when compared with WT mice in the chronic DEN model. Importantly, they also displayed a higher percentage of PCNA+ proliferative tumours, indicative of a more aggressive tumour phenotype. Immune cell infiltration including monocytes, macrophages and neutrophils was significantly increased in Nfkb1hep-/- mice. These data provide strong evidence that NFKB1 acts as a hepatocyte-specific tumour suppressor, playing an essential role in the control of inflammation, tumour initiation, progression and proliferation.MR

    Regulation of human graft versus host disease by innate lymphoidcells

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    PhD ThesisAllogeneic haematopoietic stem cell transplant (HSCT) remains the only curative therapy for many malignant and non-malignant diseases. Its use, however, remains limited by the morbidity and mortality caused by graft versus host disease (GVHD). Treatment options, even where successful, often further immunosuppress the recipient and potentially reduce the effectiveness of the transplant.IL-22, a member of the IL-10 family of cytokines, is an exciting potential therapy. Its receptor is found on the key target tissues of graft versus host disease, but not on leucocytes, thereby potentially separating GVHD from the graft versus tumour effect. The role of IL-22 in GVHD, however, remains controversial. Innate lymphoid cells (ILCs), found at many of the body’s barrier surfaces, have been shown to be key producers of IL-22, but knowledge of their function in human GVHD is limited. This project has further explored the role of IL-22 and ILCs in human stem cell transplantation. ILCs were depleted from the peripheral blood by transplant conditioning, and were predominantly of donor origin by Day 28. No difference was demonstrated in ILC recovery betweenpatients who did and did not develop acute GVHD. No evidence was found of IL-22 induction by conditioning therapy, either full or reduced intensity, in the serum or skin, but serum IL-22 concentration was increased in GVHD. In addition,an IL-22 polymorphism study found a greater risk of death from GVHD where the donor had a ‘high IL-22 producer’ genotype.Finally rIL-22 was tested in a skin explant model of GVHD and supraphysiological concentrations of IL-22 reduced the GVHD Grade in 50% of experiments performed.This project has further elucidated the role of ILCs and IL-22 in human GVHD and supports the potential for a therapeutic role for rIL-22 in this context

    ‘Let the people sing!’ : aspects of choir culture from Tyne to Tweed, 1852-1989

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    Ph. D. Thesis.This study traces the history of choral singing in Newcastle and its environs from 1852 to 1989. Following the Music Festival of 1842 there was a lull in the musical life of Newcastle until the arrival of William Rea, appointed as organist to the town corporation. Galvanizing musical activity, Rea was at the centre of a vigorous, if sometimes turbulent, choral scene in the last decades of the century. In the 20th century Armstrong College, then part of Durham University, afforded the scholarly environment for the establishment of the Newcastle Bach Choir, espousing the music of Bach and contemporary British composers. Traditional ‘oratorio’ choirs also flourished until waning interest in their basic repertory saw their demise in the 1970s and 1980s. The two World Wars had meanwhile caused some choirs to cease their activities, either temporarily or permanently, while others strengthened their presence, ensuring the continuity of choral music performance. The second half of the century saw the founding of new choirs, including the Cappella Novocastriensis, strongly linked to the University, and two choirs formed to support orchestras wishing to perform choral works. Alongside this mainstream choral activity, male-voice choirs developed, a number rooted in their works communities or nonconformist and temperance environments. Their repertory, aims and organisation contrasted strongly with the established mixed-voice choirs. The choral life of Northumberland centred on one or two regional ‘clusters’; the comparative isolation of Berwick upon Tweed, the most northerly Northumbrian town, encouraged strong indigenous musical activity. A survey of the venues used for concerts and rehearsals underlines the want of suitable halls in the area, while an account of the orchestras used shows the challenges imposed by the lack of an accommodating local professional orchestra and the increasing use of period instruments for performances of baroque music

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