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    5357 research outputs found

    Modelling escalation of attacks in federated identity management

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    PhD ThesisFederated Identity Management (FIM) is an increasingly prevalent method for authenticating users online. FIM offloads the authentication burden from a Service Provider (SP) to an Identity Provider (IdP) that the SP trusts. The different entities involved in the FIM process are referred to as stakeholders. The benefits of FIM to stakeholders are clear, such as the ability for users to use Single Sign-On. However, the security of FIM also has to be evaluated. Attacks on one point in a FIM system can lead to other attacks being possible, and detecting those attacks can be hard just from modelling the functionality of the FIM system. Attacks in which the effect of one attack can become the cause for another attack are referred to in this thesis as escalating attacks. The overall research question this thesis revolves around: how can we model escalating attacks to detect attacks which are possible through an adversary first launching another attack, and present causality of attacks to the FIM stakeholders involved? This thesis performs a survey of existing attacks in FIM. We categorise attacks on FIM using a taxonomy of our own design. This survey is the first attempt at categorising attacks that target FIM using a taxonomy. Some attacks can have an effect that causes another attack to be possible in ways that are difficult to predict. We consider a case study involving OAuth 2.0 (provided by existing literature), as a basis for modelling attack escalation. We then seek to present a language for modelling FIM systems and attacker manipulations on those systems. We find that FIM systems can be generalised for the purpose of a programmatic logical analysis. In addition, attacker manipulations on a system can be broken down using an existing conceptual framework called Malicious and Accidental Fault Tolerance (MAFTIA). Using a generalised FIM system model and MAFTIA, we can express a complex interlinking of attacks informed by case studies in FIM security analysis. This is the first attempt to model FIM systems generally and apply logical analysis to that model. Finally, we show how causality of attacks can be analysed using attack trees. We find that any solutions to an escalating attack can be expressed using a tree model which conforms to existing research on attack trees. Our approach is the first attempt of modelling attacks on FIM systems through the use of attack trees. We consider stakeholder attribution and cost analysis as concrete methods for analysing attack trees

    Fundamental Understanding of Turbulent Combustion in Droplet-Laden Mixtures Using Direct Numerical Simulations

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    PhD ThesisThe flame propagation in droplet-laden mixtures is of considerable importance in automotive engines, gas turbines, and accidental explosions. Despite the practical importance of turbulent combustion of droplet-laden mixtures, it remains one of the most challenging topics in thermo-fluid mechanics due to the involvement of complex interactions of evaporation, heat and mass transfer, fluid dynamics, and combustion thermochemistry. Thorough knowledge of these interactions, which occur over a wide range of scales, is necessary for fundamental understanding and modelling of turbulent spray flames. In this thesis, three dimensional compressible Direct Numerical Simulations (DNS) of spherically expanding and V-shaped flames propagating in droplet mists are considered for a fundamental physical understanding of the flame structure and flame speed statistics in turbulent spray flames. Simulations with modified single-step Arrhenius type chemical mechanism have been conducted for a range of different droplet diameters, overall equivalence ratios, and turbulence intensities. The influence of liquid droplets has been investigated by comparing the statistics for spray flames to those for the corresponding gaseous premixed spherically expanding flames with statistically similar initial turbulent flow conditions. It has been found that flame-droplet interaction promotes dropletinduced flame wrinkling for laminar flame kernels, and this strengthens with increasing overall equivalence ratio and droplet diameter. However, the effects of droplet-induced flame wrinkling cannot be readily distinguished from flame wrinkling due to fluid motion for turbulent spherically expanding spray flames. The combustion has been found to take place predominantly under fuel-lean mode in comparison to the overall equivalence ratio for all droplet sizes and this tendency strengthens with increasing droplet diameter due to slow evaporation of large droplets. Furthermore, increasing turbulence intensities enhances the availability of fuel-lean mixture. The statistics of the Surface Density Function (SDF = magnitude of the reaction progress variable gradient) and the strain rates, which affect the behaviour of SDF have been analysed for spherically expanding spray flames. Flame thickening has been observed for large droplets and at high turbulence intensities due to the predominance of fuel-lean combustion. Droplet size and turbulence intensity significantly affect the behaviour of scalar gradients and the infinitesimal distance between non-material surfaces. The flame propagation behaviour in droplet-laden mixtures has been analysed in terms of the statistics of density-weighted dis- placement and consumption speeds. Flame topologies associated with flame self-interaction events have been discussed along with the small-scale scalar geometries of flame isosurfaces. The presence of droplets, turbulence intensity and droplet diameter have been found to considerably alter the distributions of flame topologies. Additionally, flame-droplet interactions have been investigated in detail based on the source terms associated with two-phase coupling arising from droplet evaporation in various gaseous carrier phase transport equations and the modelling implications of the statistical behaviour of flame-droplet interactions have been addressed. Furthermore, hypothetical inertialess droplet motion is considered to identify the influence of droplet inertia on the combustion characteristics and the evolution of the flame surface area. The number density of droplets within the flame is greater for the inertial droplet cases than the corresponding inertialess droplet cases and this leads to higher availability of obtaining stoichiometric mixture in the flame. Finally, a comparison between the spherically expanding and V-shaped spray flames reveals that flame curvature, density-weighted displacement speed, and consumption speed varies considerably with droplet diameter in the case of spherically expanding spray flame cases, whereas the effects of droplet diameter are relatively weaker in V-flames. Simulations of V-shaped flames propagating in droplet mists for different mean inflow velocities indicate that reacting mixture composition significantly varies with the mean inflow velocity which also plays an important role in determining the flame structure and burning rate statistics

    Equilibrium and Uptake Kinetics of Copper and Cadmium ions by the Microalgae, Chlorella vulgaris and Scenedesmus obliquus

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    Ph. D. Thesis.The removal of heavy metals from wastewater is an important step in a wastewater treatment process. Some metals are essential minerals, but others such as copper and cadmium are toxic when consumed. Microalgae have been identified as organisms that can tolerate and accumulate heavy metals. This tolerance offers a potential mechanism for metal removal that is cheaper and more efficient than current conventional methods. In this research, two species of microalgae, C. vulgaris and S. obliquus were exposed to water that was contaminated with copper and cadmium at concentrations of 0.25, 0.5, 0.75 and 2.5mg.L-1 . The binding capacity of the microalgae biomass to the metal ions increased linearly with the size of the ratio of the initial concentration of the metal ions to the initial concentration of the microalgae. The total metal ion removal from solution appeared to be independent of initial concentrations however, with C. vulgaris removing between 88% and 90% of the copper with all concentration combinations investigated. Based on equilibrium studies, the Freundlich Isotherm was concluded to best represent the experimental data. The linear Freundlich isotherms had R2 values greater than 0.98 for all experiments, and the Freundlich Isotherm assumptions relate more to the heterogeneity of the algae surface. The Langmuir isotherm showed a stronger linear correlation with R2 values greater than 0.99 in all cases, but did not produce realistic model parameters for the adsorption of copper by C. vulgaris. The adsorption kinetics of the metals were investigated and compared by fitting the Lagergren, Second-order model, the Elovich model and a kinetic expression derived from the Langmuir Isotherm to the experimental data. The second order model was found to fit experimental data more accurately than the Elovich and the Lagergren models when parameters were obtained by linearising the data. The Langmuir rate equation was approximated to the Lagergren model and the second order model, and based on the analysis the Lagergren model with parameters derived from the Langmuir Isotherm was most appropriate to model metal adsorption by S. obliquus. ii The current study analysed techniques used to compare the binding capacities of C. vulgaris and S. obliquus, and determined that both species were successful adsorbents for copper and cadmium. It was concluded from the rate expressions that C. vulgaris adsorbed the metal ions at a faster rate than S. obliquus, and has a higher capacity to both metal species. This would suggest that out of the two species of microalgae, C. vulgaris would be most suitable for metal removal for wastewater treatment purposes

    The development of vocabulary, working memory and phonological awareness among Kuwaiti Arabic individuals with Down syndrome and typically developing children

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    Ph. D. Thesis.A large body of research has focused on language development throughout childhood among typically developing (TD) children due to its importance for communication, expressing feelings and needs, and maintaining relationships. Most research on language development within the context of intellectual disability, such as Down syndrome (DS), has been conducted among English speakers. However, there is a lack of research examining how trajectories among Arabic-speaking DS individuals might differ. This study employed a cross-sectional developmental trajectory approach to investigate vocabulary, phonological short-term memory and phonological awareness (PA) in relation to non-verbal mental ability as measured by Ravens Coloured Progressive Matrices (RCPM) raw scores in Gulf Arabic (Kuwaiti) DS and TD groups. It also addressed the relationships between phonological awareness and vocabulary knowledge (related to the lexical restructuring [LR] model), as well as theorized relationships between phonological short-term memory and vocabulary, and phonological short-term memory and phonological awareness. Forty-eight individuals with DS aged 6–20 years old were matched on RCPM with 44 TD children aged 3–10 years old. Data were collected for each participant in two sessions, assessing phonological short-term memory using a non-word recognition (NWR) test, testing receptive and expressive vocabulary, and assessing phonological awareness at the level of syllable, rhyme and phoneme. The findings show a similar onset and rate of development in PA and vocabulary across nonverbal mental ability for the DS and TD groups, but not in phonological short-term memory. In addition, there is a strong correlation between non-verbal mental ability (NVMA) and these skills in the DS group, but not with phonological short-term memory. Significant correlations between NVMA and some language skills would be predicted by neuro-constructivist theory, while further findings showing an association between vocabulary and phonological awareness to a similar extent across the DS and TD groups are in line with the LR model. Another important finding is that phonological short-term memory is associated with phonological awareness in different ways in the DS and TD groups. Moreover, phonological short-term memory is not significantly correlated with non-verbal mental ability or vocabulary measures in the DS group, implying that NWR plays no part in vocabulary development for individuals with DS. In contrast, there is a strong correlation between phonological short-term memory and vocabulary in the TD group, consistent with the phonological short-term memory theory. The educational, clinical and policy implications discussed highlight the need for further study in this area, as well as for standardized Arabic tests

    Poor oral health and age-related health outcomes : epidemiological cohort studies of older people in the United Kingdom and United States of America

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    PhD ThesisOral health problems have been found to be associated with disability, poor physical function, and mortality. However, cross-sectional and prospective associations are not well-established in older people, especially for self-reported oral health problems. Diet and inflammation are potential mediators in the association between poor oral health and risk of disability. However, evidence is limited. Additionally, gaps exist in the associations of poor oral health with different inflammatory markers. Inconsistent findings have also been reported for the associations between oral health and diet in older people. This thesis uses data from two population-based studies of older people, the British Regional Heart study (BRHS) and the US Health, Aging and Body Composition (HABC) Study. Data have been used to investigate cross-sectional associations of oral health problems with disability, physical function, inflammatory, haemostatic, and cardiac biomarkers, diet quality and dietary intake, and prospective associations of oral health with risk of disability, all-cause, cardiovascular disease (CVD), and respiratory mortality in older people. Oral health problems included objective (tooth loss, periodontal disease), and subjective (dry mouth, self-rated oral health) assessments and accumulation of oral health problems. Causal mediation was performed to test mediation through diet and inflammation. The main findings are that oral health problems were cross-sectionally associated with disability and poor physical function. Poor oral health (tooth loss, periodontal disease, dry mouth, cumulative oral health problems) was also associated prospectively with greater risk of developing disability, and all-cause, CVD and respiratory mortality. Some oral health problems were associated with increased inflammation, poor diet quality and poor nutritional intake. However, inflammation and diet did not appear to mediate the association of poor oral health with risk of developing disability. Finally, poor oral health is potentially an important risk factor for the onset of disability and all-cause and cause specific mortality in older people.British Heart Foundation, Dunhill Medical Trust, National Institute on Aging, National Institute of Nursing Research, and National Institute of Dental and Craniofacial Research

    The use of treosulfan in conditioning for haematopoietic stem cell transplantation in children with primary immunodeficiency

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    Ph. D. Thesis.Primary Immunodeficiencies (PIDs) are inherited disorders that lead to defects in the development and/or function of the immune system. The number of disorders that can be treated by haematopoietic stem cell transplantation (HSCT) has increased rapidly with the advent of next generation sequencing. The methods used to transplant children with PID have improved dramatically over the last 20 years. The introduction of reduced toxicity conditioning is an important factor in the improved outcome of HSCT. Treosulfan has myeloablative and immunosuppressive properties, enabling engraftment with less toxicity than traditionally used doses of busulfan. The use of treosulfan in conditioning prior to HSCT for children with PID is reported in this thesis. Six published works are presented. The first 2 provide background with up to date information on HSCT and conditioning regimens in children with PID. The increased use of low toxicity treosulfan-based combinations is demonstrated in published paper PP3 which is the largest published series to date of patients with non-malignant disorders who received treosulfan-based conditioning across Europe. The place of treosulfan in conditioning patients specifically with Chronic Granulomatous Disease from centres worldwide is presented in PP4. Close collaboration with Great Ormond Street Hospital, London has led to rigorous monitoring and step by step improvements in the approach to transplant using treosulfan, published in Supplementary paper 1, followed by PP5 and culminating in a prospective pharmacokinetic study presented in PP6, which is the first study to demonstrate an association with high area under the concentration curve (AUC) and increased mortality, and low AUC and poor engraftment. For each manuscript I present an overview of the study, what was known before, and what the study added to the literature, my contribution to the work and a short discussion of the strengths and limitations. Treosulfan has been established as a safe and effective agent for conditioning children with PID prior to HSCT. It is firmly incorporated into the conditioning guidelines of the Inborn Errors Working Party of the European Society for Blood and Marrow Transplantation. The works presented in this thesis demonstrate the contribution that I have made to the field, and pave the way for future research. It is likely that individualized dosing, not just of treosulfan, but of all agents used in conditioning regimens, will be developed and implemented. This will lead to a reduction in unwanted variability in drug exposure, leading to more predictable and adjustable exposure, and improved outcome of HSCT, with fewer late adverse effects and improved quality of life. Such conditioning regimens can be used as the basis to study the need for additional agents in certain disorders, the dosing of individual cellular components within grafts and effects of adjuvant cellular or immunotherapy post-transplant

    Investigating the effect of age-related mitochondrial dysfunction on intestinal tumour formation and progression

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    Ph. D. Thesis.The clonal expansion of mitochondrial DNA (mtDNA) point mutations and associated defects of oxidative phosphorylation (OXPHOS) are observed within the ageing colorectal epithelium. Clonally expanded mtDNA point mutations are also observed within colorectal tumours, however whether these mutations are passive bystanders or if they functionally contribute to tumour progression is unknown. In order to address this, a mouse model was developed in which PolγA mediated mtDNA mutation accumulation preceded the intestinal Lgr5+ stem cell specific deletion of Apc. In comparison with controls, mice harbouring OXPHOS defects demonstrated an accelerated clinical deterioration characterised by anaemia, impaired thermoregulation and weight loss. The reduced survival of these animals was attributed to a significantly greater intestinal adenoma burden in which a prominent complex I defect was revealed following immunofluorescent quantification of OXPHOS protein levels. A double thymidine analogue labelling technique demonstrated accelerated proliferation within complex I deficient intestinal adenomas while apoptotic cells were significantly fewer. Total RNA sequencing of OXPHOS deficient intestinal crypts prior to Apc deletion identified the upregulation of transcripts specific to the de novo serine synthesis pathway and mitochondrial one-carbon cycle (Whitehall, 2019). These pathways provide essential nucleotides, antioxidants and anabolic precursors vital to maximal tumour growth. RNA sequencing results were validated at the protein level within OXPHOS deficient intestinal crypts and adenomas and were further demonstrated to be upregulated in response to an age-related accumulation of OXPHOS defects in the murine small intestine and colon. Finally, these data are directly translatable to the normal human colonic epithelium in which the upregulation of serine synthesis and mitochondrial one-carbon cycle enzymes was identified within OXPHOS deficient crypts. These data show that age-related OXPHOS deficiency creates a permissive metabolic environment which in the event of malignant transformation, can actively contribute to accelerated intestinal cancer growt

    Synthesis and Evaluation of Photoactivatable D-Amino Acid Probes of Bacterial Peptidoglycan Biosynthesis

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    Ph. D. Thesis.The bacterial cell wall contains peptidoglycan (PG), a mesh-like polymer of glycan strands crosslinked by short peptide chains. PG is essential for bacterial cell viability and as such PG biosynthesis is an important antibiotic target. Despite considerable study, there remain many PG associated enzymes with unknown function, identification of which will allow us to develop the antibiotics of the future. This project is focused on the development of D-amino acid based photoaffinity probes, for the covalent capture of PG associated proteins. Following the evaluation of a number of strategies, a photoactivatable fluorescent D-amino acid probe was successfully synthesised, methoxy coumarin trifluoromethyl diazirine D-alanine or MCTDA.Addionally it can be shown by LCMS that MCTDA is accepted as a substrate by the bacterial transpeptidase enzyme LdtD and that, through the action of LdtD, MCTDA can be successfully incorporated into both isolated muropeptide and whole PG of E. coli. Evaluation of photoactivated capture of PG associated proteins by incorporated MCTDA is ongoing in the laboratory (Figure 1). (please see electronic version of thesis for figure1.) Figure 1: Synthesis of photoactivatable amino acid probe MCTDA and incorporation into PG and muropeptide (E. coli) by LdtD

    Exploring ‘Epistemologies of Reading’ Using Adam Smith’s ‘Invisible Hand'

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    Ph. D. Thesis.This thesis demonstrates the inherent and inalienable role that a reader’s epistemological commitments play in their reading of historical concepts. To make this argument, I examine the plethora of different readings of Adam Smith’s ‘invisible hand’. We see in these readings an illustration of a trend ubiquitous throughout academia: the production of a historical lineage for an idea or theory through the process of reading and then invoking a historical predecessor. Readings of the ‘invisible hand’ from 1759 to 2017 are examined and the epistemological commitments of their authors are shown to shape and condition them, in other words, I identify what I call ‘Epistemologies of Reading’. The term ‘Epistemologies of Reading’ denotes the phenomenon of how an individual’s conception of knowledge, what they believe constitutes valid knowledge and how this can be attained and measured, impacts upon their reading process. Relatedly, an individual’s ‘Epistemology of Reading’ is simply the specific way in which their epistemology impacts upon their reading. The thesis proceeds in three steps. I begin by identifying the various readings of the ‘invisible hand’ that have occurred since Smith’s first use of the phrase in Theory of Moral Sentiments, published in 1759. I then group these into seven ideal-type readings on the basis of their shared characteristics. In a second step, I identify the epistemological frameworks that shape and condition these readings, using an intertextual, symptomatic approach. In a final step, I employ the work of Quentin Skinner to perform a theoretically grounded evaluation of these types and their associated epistemological commitments. This project is underpinned by a conceptual framework comprised of the approaches of Karl Mannheim, Reinhart Koselleck and Quentin Skinner: combined, these scholars provide a conceptual toolbox with which I have been able to understand and articulate the existence of different ‘Epistemologies of Readings’ of the ‘invisible hand’. In undertaking this research, my thesis contributes to two bodies of literature. Firstly, my identification of ‘Epistemologies of Reading’ represents a contribution to the literature on methods of intellectual history – in particular, the work of Quentin Skinner and Mark Bevir. I add to their discussions relating to extracting meaning from a text, specifically through accessing an author’s ‘mental world’ or ‘web of beliefs’. Secondly, my focus on Adam Smith’s ‘invisible hand, and my unpacking of the numerous readings of this phrase, represents my contribution to the body of contemporary revisionist literature, as these scholars focus specifically on revising mainstream interpretations of Smith. This microstudy of economic knowledge formation demonstrates the decisive role played by epistemological frameworks in the reading process. As a consequence of this, I make the normative claim that to adequately and comprehensively understand an individual’s reading of a historical figure or their work, one must incorporate an epistemological analysis, understanding it not as an independent activity but rather as being epistemologically conditioned.ESR

    Structure-function relationships in stressosome complexes from Listeria monocytogenes and Bacillus subtilis

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    PhD ThesisListeria monocytogenes is a foodborne bacterial pathogen that can resist and overcome extreme environmental conditions, such as the extremes of temperature, salinity and pH that are encountered during food processing. Stress resistance is regulated by a supramolecular protein complex called the stressosome, which detects and integrates environmental stress signals that induce a partner-switching and phosphorylation cascade leading to the activation of an alternative RNA polymerase sigma factor, σB, which controls a regulon of ~200 genes involved in the general stress response. The stressosome comprises three main proteins, RsbR (which has four paralogues), RsbS and RsbT. The N-terminal domains of RsbR proteins have been proposed to act as stress sensors and they project from the core of the stressosome as ‘turrets’. However, the mechanism by which signals are perceived and transmitted is still unknown. Structural studies of the stressosome’s sensory domains resulted in the successful determination of the crystal structures of N-RsbR1, N-RsbR2, and N-RsbR3. Ligand binding pockets were identified in N-RsbR3 that yield insight into signal perception and transduction mechanisms. The interaction of the Prli42 miniprotein with N-RsbR proteins was also assessed and shown not to occur at biologically-relevant concentrations. Common ligands and drug-like fragments were screened against binding to the putative ligand binding pocket and candidate interacting molecules were identified. Native stressosomes pulled-down from B. subtilis cell lysates by affinity purification contained all four RsbR paralogues, along with RsbS and RsbT. Initial electron microscopy of the purified native stressosomes were consistent with the formation of a highly symmetric structure. Purification and EM studies of stressosome variants revealed that stressosomes can be formed by any of the RsbR paralogues. Stressosome variants were analysed by cryo-EM single particle analysis, which showed that the RsbR-RsbS complex displays similar features to the known stressosome complex of B. subtilis, albeit with markedly different stoichiometries

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