text: DSpace Collection: http://hdl.handle.net/2381/8806 2015-07-08T04:43:33Z Modelling biological macromolecules in solution: the general tri-axial ellipsoid http://hdl.handle.net/2381/32509 Title: Modelling biological macromolecules in solution: the general tri-axial ellipsoid Authors: Harding, Stephen Ernest Abstract: Hydrodynamic shape functions for modelling biological macromolecules in solution in terms of an ellipsoid of revolution model are reviewed. Several new, hitherto unpublished shape functions whose experimental determination does not require knowledge of the swollen molecular volume in solution, are given. The limitations and inadequacies of this model are explained. The viscosity increment v for a dilute dispersion of tri-axial ellipsoids of semi-axes a> b> c, under dominant Brownian motion is derived and an explicit expression in terms of a, b and c is given. Knowledge of the viscosity increment alone is not sufficient to uniquely determine the axial ratios (a/b, b/c) because (i) in order to determine v, knowledge of the swollen volume in solution is required and (ii) a particular value for v has a line solution of possible values for (a/b, b/c). (i) is dealt with by combining v with the tri-axial frictional ratio function P to give the tri-axial R function and (ii) by combining graphically the R line solution with δ+ and δ- swelling independent line solutions. The experimental determination of δ+ and δ- requires the resolution of a 2-term electric birefringence decay into its component relaxation times; current data analysis techniques are however not satisfactory for resolving close relaxation times (as for globular proteins) with the current experimental precision. It is however shown by exhaustive computer simulation that using a new R-constrained nonlinear least squares iterative analysis this is now possible. It is thus concluded that the general tri-axial ellipsoid as a model for the gross conformation of biological macromolecules in solution can now be employed. 2015-07-07T15:36:16Z Violent Men: Investigating Mental Disorder, Substance Use and PTSD http://hdl.handle.net/2381/32508 Title: Violent Men: Investigating Mental Disorder, Substance Use and PTSD Authors: Thomas, Glen Abstract: This study considered the relationship between mental disorder, substance use, violence, trauma and posttraumatic stress disorder (PTSD) problems in a sample of male patients within a mental health directorate of a high secure hospital. All patients admitted to the service in the five years prior to March 2010 were considered for the study. A total of fifty-two patients were approached to participate in the study, of which 32 consented, representing 25% of all patients in the service. Multiple methods of assessment incorporating both qualitative and quantitative approaches were used to gather information on mental health, substance misuse, violence, and trauma and posttraumatic stress disorder problems. A full data set was completed for twenty-eight patients and a partial data set for a further four. The sample was found to have a considerable history of poly-drug use, previous contact with psychiatric services, and convictions for serious violence. Differences were found between patients with a paranoid schizophrenia and schizophrenia diagnosis in relation to, types of drugs used and dependency to drugs, with drug preference and sensitivity to drug effects being found to differ between the two groups. A relationship was also found between type, level, frequency and dependency to a number of drugs and frequency and type of violence convictions which differed between diagnostic groups. Likewise, previous psychiatric and custodial history was also found to be associated with substance use and violence convictions. The sample also had an extensive trauma history and while rates of PTSD were low, the prevalence of sub-clinical PTSD symptoms was found to be extensive. PTSD problems were found to be associated with mental health and substance misuse problems, and some instances of violence. These findings suggest that PTSD related difficulties need to be considered when looking at substance misuse in people with a severe mental health diagnosis. Description: Due to third party copyright restrictions the following extracts have been removed from the appendix of the electronic version of this thesis: Appendix 9 - Brief Symptom Inventory (BSI) by Leonard R. Derogatis, PhD Appendix 10 - Structured Interview for Disorders of Extreme Distress (SIDES) by David Pelcovitz et al. Appendix 11 - Detailed Assessment of Posttraumatic Stress (DAPS) - Item Booklet developed by John Briere, PhD and PAR Staff The unabridged version can be consulted, on request, at the University of Leicester's David Wilson Library. 2015-07-07T13:31:37Z Design and evaluation of a predictable embedded processor for use in timetriggered applications http://hdl.handle.net/2381/32507 Title: Design and evaluation of a predictable embedded processor for use in timetriggered applications Authors: Hughes, Zemian Abstract: Embedded processors play a key role in many safety-critical applications including medical, automotive and aerospace systems. In such systems an inability to provide guarantees that the design will meet its requirements can have catastrophic consequences. To ensure that guarantees can be made, it must be possible to predict both the functional and temporal properties of the system at design time. The trend in modern embedded system design is currently leading towards unpredictable processor architectures in order to achieve increased performance. This trend presents fundamental challenges for the designers of timing analysis tools who are finding the accuracy and safety of timing estimations produced by new tools are getting worse. The consequence of this is that it is increasingly becoming harder to provide guarantees that the system requirements will be met. The primary causal factor is put down to the developments in modern processor architecture. This thesis attempts to address these problems with a novel, highly predictable embedded processor design for systems with a "time-triggered" (TT) system architecture. Even with a predictable processor, a real-time operating system (RTOS) implemented in software can itself complicate the temporal predictability of the system. To address this issue a predictable hardware TT scheduler is implemented in hardware. In order to overcome the possibility of the application programmer writing temporally unpredictable code, a set of software-based error-detection (and recovery) mechanisms is implemented as a "task guardian" to deal with issues of task overruns in TT systems. The performance and complexity of the initial software implementation leads to an innovative hardware task guardian solution. Overall, the implication of the studies presented in this thesis provide the system developer with an effective set of software and hardware components which are shown to provide a highly-predictable platform for the execution of time-triggered tasks sets. 2015-07-07T13:25:16Z Use of regolith geochemistry to delineate gold mineralisation under cover: a case study in the Lawra belt, NW Ghana http://hdl.handle.net/2381/32506 Title: Use of regolith geochemistry to delineate gold mineralisation under cover: a case study in the Lawra belt, NW Ghana Authors: Arhin, Emmanuel Abstract: The Birimian rocks of southern Ghana host world-class gold deposits yet no equivalent-sized deposit has been found in the Birimian rocks in northwest Ghana. The reported gold occurrences in the area suggest a favourable environment for concealed mineralisation if the regolith and landscape evolution can be unravelled. A geochemical exploration model based on the evolution of the regolith-landform can help guide the choice of exploration methodology appropriate for the region. The developed regolith map classifies the landscape into ferruginous (F), relict (R), erosional (E) and depositional (D) domains. Depositional areas cover 72% whereas the remaining 28% represents residual environments. Discrimination, characterisation and identification of regolith materials were carried out by pit and outcrop mapping. Regolith geochemical data provided regolith profile information which helped to distinguish residual regolith from transported types. Binary plots of major and trace element geochemical data were used to determine the compositional variability and different regolith types. Superimposing geochemical data on the regolith map identified residual and transported anomalies, and thus prioritized the weak, subtle and discontinuous anomalies. Gold, Ag and As relations in the regolith were also useful in determining the anomaly type and presence of gold mineralisation. High Au-low Ag with smooth dispersal patterns represents residual anomalies whereas spiky dispersion patterns with high Au-high Ag characterize transported anomalies. The released As into the regolith appears counteracted by the precipitation of Fe-oxyhydroxides, which efficiently scavenge As3+ and As5+ at neutral pH in the regolith, resulting in the weak As concentrations in the analysed samples. Hence it may not be an appropriate pathfinder element for Au in the study area. The regolith mapping techniques devised for the study can be used to map complex regolith terrains. The landscape evolution model developed for the area will provide useful insight into the irregular distribution of the regolith and help in designing exploration techniques suitable for the Lawra belt and similar complex regolith terrains of the savannah regions. 2015-07-07T11:35:54Z Remote sensing-based mapping and modelling of salt marsh habitats based on optical, lidar and sar data http://hdl.handle.net/2381/32455 Title: Remote sensing-based mapping and modelling of salt marsh habitats based on optical, lidar and sar data Authors: van Beijma, Sybrand Jucke Abstract: There is much interest in the ability of Remote Sensing (RS) technologies for mapping natural environments. Meanwhile, coastal zones need monitoring in order to find a balance between human use and sustainable functioning of coastal zone ecosystems. This research explores methods for characterising coastal salt marsh zone habitats using multi-source RS data, focussing on under-exploited Synthetic Aperture Radar (SAR) remote sensing data, thereby providing additional information in support of the mapping of natural habitats in coastal zones. This research examined the use of quad-polarimetric airborne S-band and X-band SAR data, in conjunction with optical and LiDAR RS data variables, for assessment of environmental parameters, mapping and modelling of salt marsh habitats in a research area set in the Llanrhidian salt marshes in Wales. In the first analysis it was researched how SAR descriptors (backscatter intensity and polarimetric decomposition variables) were affected by salt marsh environmental and botanical factors. It was found that SAR backscatter from the most seaward pioneer zone of the salt marsh was most affected by soil moisture variations. Differences in botanical structure caused variations in SAR backscatter mechanisms active in different habitats. In the second analysis habitat mapping was carried out with optical, LiDAR and SAR variables, with the supervised classifiers Support Vector Machine (SVM) and Random Forest (RF). With these classifiers accurate salt marsh habitat maps were produced, the most accurate classification achieved was 78.20% with RF based on all available RS variables. The last research experiment involved multivariate regression analysis of correlations between RS variables and biophysical parameters vegetation cover, height and volume and showed that multivariate SVM regression was the most accurate technique for all three biophysical parameters. This research indicated that SAR is complementary to optical and LiDAR data for ecological mapping and therefore recommended to be included in similar ecological studies. 2015-06-30T11:21:12Z How can children's centre leaders best enable integrated working to flourish? http://hdl.handle.net/2381/32454 Title: How can children's centre leaders best enable integrated working to flourish? Authors: Vaggers, Julie Abstract: Early, effective and integrated public service responses to the needs of children and families continue to be a cornerstone of National Policy. Children's centres are local resources offering a range of services across health, education and social care in order to improve the life chances of children and their families. Leadership is known to be the key to successful collaboration, bringing together people who have not worked together before. This research aimed to explore the challenges of leading an integrated children's centre. The research used a qualitative methodology to identify new understandings about leadership approaches. It identified the barriers that prevented effective collaboration and developed a model to analyse and shift the current state of integration. It explored the meaning of integrated services and how leaders could establish a climate for collaboration. Five strategic managers were interviewed. The main findings were that the concept of integrated services was unfamiliar and open to interpretation. Centres offered professionals an opportunity to be part of a learning community where they could share knowledge and build relationships. Ten centre leaders took part in eight action learning sets. The main findings were that centres enabled staff to share knowledge and develop a shared purpose. Services needed to be well planned over a locality. Leaders needed to have a clear understanding about their own and others behaviours and learning needs. The final synthesis of these outcomes was that four leadership processes were developed which could help leaders to enable integrated working to flourish. These were: thinking systemically, building and rebuilding relationships, nourishing self actualisation and utilising alternative approaches to solving complex problems. The outcomes from this research mean that it will be possible for leaders to test out and explore new ways of leading a children's centre. 2015-06-30T11:15:21Z The plasma proteome and outcome in patients with heart failure http://hdl.handle.net/2381/32453 Title: The plasma proteome and outcome in patients with heart failure Authors: Thong, Cao Huy Abstract: Heart failure is a complex clinical syndrome that occurs at the end stage of heart disease with high costs and poor outcomes. Despite advances in therapy, improving clinical outcomes remains a challenge for physicians with 50% of patients dying within 5 years. The main aim of this study was to discover novel biomarkers in plasma that could predict treatment response in patients with heart failure using plasma proteomics. The use of two dimensional liquid chromatography coupled to electrospray ionisation tandem mass spectrometry in high definition ion mobility combined with a multiple affinity removal system column and immunoluminometric assay discovered CD180 antigen, Heat shock 70 kDa protein 4L, Leukemia inhibitory factor receptor and Neurotrimin as novel biomarkers which are able to predict treatment response in patients with heart failure. Moreover, Thyroid receptor interacting protein 11, Patatin like phospholipase domain containing protein 2 and Mannan binding lectin serine protease 2 were identified as novel biomarkers for prediction of death in patients with heart failure. Furthermore, two multiple biomarker models were developed from the findings obtained of using matrix assisted laser desorption ionisation mass spectrometry combined with C18 solid phase extraction which are able to predict treatment response in patients with heart failure. The model with seven peptide peaks showed an excellent area under the receiver operating characteristic curve (AUC) of 0.907. In particular, the model with seventeen peptide peaks achieved the maximum AUC of 1.000 (100% sensitivity and 100% specificity). The discovery of novel biomarkers in this study not only adds information to understand the pathophysiological mechanisms of heart failure better, but also may provide a more accurate prediction of treatment response to guide medical therapy. This may enable the practice of stratified medicine in the future. Moreover, novel therapeutic targets could be identified for design of new drugs to improve outcomes. 2015-06-30T11:10:57Z Studies of the proteins involved in the formation of early spliceosomal complexes http://hdl.handle.net/2381/32452 Title: Studies of the proteins involved in the formation of early spliceosomal complexes Authors: Smith, Paul Abstract: The spliceosomal E complex is the first spliceosomal complex that is committed to pre-mRNA splicing and therefore the components of this complex are early targets for regulation. With the majority of splicing regulation occurring at these early stages a greater understanding of these early complexes will bring a greater understanding of how splicing is regulated. Even at this early stage the functional groups at either end of the intron are in close proximity but the proteins involved in bringing the splice sites together are still poorly characterised. This thesis studied three distinct threads: the first thread investigated the interactions of one of the proposed bridges between the two splice sites, PRPF40A. Interaction studies in this thesis showed that the WW domains of PRPF40A were able to precipitate the U2 snRNP. The FF domains of PRPF40A were also able to interact with another component of the E complex, the SMN protein. As yet it is unclear whether the interaction between PRPF40A and SMN is a direct interaction. What was striking in this study was that no clear interaction with U1 snRNP could be seen with any of the fragments of the PRPF40A protein. This leads me to believe that, unlike yeast PRP40, PRPF40A is a U2 snRNP related protein, not a U1 snRNP protein. The second thread was to develop a new method to isolate U snRNPs using Flag-tagged U snRNP proteins; in this study the U1 snRNP was purified using Flag-tagged U1A and a U1-U2 di-snRNP was isolated using Flag-tagged U2 snRNP. This method of epitope-tagging core U snRNP proteins is useful as an alternative to antibodies for isolation of specific U snRNPs from nuclear extracts, as it gives flexibility in the target protein. The final thread was the development of a method to isolate and analyse the composition of ATP independent complexes formed on Exon and intron defined MINX constructs. The RNA composition was successfully analysed in an isolated MINX intron defined complex and an isolated MINX exon defined complex. Both exon- and intron-defined MINX constructs precipitated U1 and U2 snRNA. This study has focused on the interactions of PRPF40A; it has confirmed the interaction of PRPF40A with U2 snRNP (Makarov et al., 2012) and shown that this interaction is through the WW domains of the protein. The study has also begun to elucidate the interactions of the FF domains of the PRPF40A protein. Finally the study has developed two methods for isolating and studying the formation of the spliceosomal E complex. 2015-06-30T11:04:42Z At the water's edge: an integration of ethnographic and archaeological methods in the study of rock art in Northern Central British Columbia, Canada http://hdl.handle.net/2381/32448 Title: At the water's edge: an integration of ethnographic and archaeological methods in the study of rock art in Northern Central British Columbia, Canada Authors: Mitchell, Suzanne Abstract: Pictographs occur frequently in the landscapes of northern central British Columbia, but they have received modest academic attention. As a result, there is limited understanding of rock art as social practice and its significance within larger cultural landscapes. This research integrates First Nations traditional knowledge with archaeological data in order to investigate the waterscape context and iconography of pictographs across three First Nations traditional territories. The insights into the rock markings provided by First Nations elders offer important informed perspectives about the images and the landscape that, when combined with archaeological data and formal analytical processes, enable the study of the social understanding of rock art and its context within the expansive territories of this region. 2015-06-29T15:18:15Z Community radio as a tool for development: a case study of community radio stations in Malawi http://hdl.handle.net/2381/32447 Title: Community radio as a tool for development: a case study of community radio stations in Malawi Authors: Mhagama, Peter Matthews Abstract: The thesis investigates community radio as a tool for development drawing on case studies of Nkhotakota and Mzimba community radio stations in Malawi. The thesis employs communication for development and 'another' development theories to help understand the role of community radio in development. The research aims are firstly, to investigate the extent and ways in which community radio is used as a tool for development through audience participation; and secondly to examine the extent to which communication for development in community radio in Malawi takes the form of participatory communication. Using the case study approach (Yin, 2009), the thesis specifically examines the functions of participation in development through community radio; whether community radio can encourage development through enhancing capabilities and participation even when people do not own and manage the stations; how radio listening Clubs (RLCs) help to expand people's capabilities; and how the programming of community radio in Malawi is influenced by the agendas of development agencies. Arnstein's (1969) ladder of participation and Carpentier's (2011) minimalist and maximalist versions of participation are adopted as criteria for evaluating the different levels of participation in and through community radio. The findings show that community radio in Malawi firstly, affords ordinary people opportunities to participate in the media and in development projects and, secondly informs people about development initiatives from development agencies. Although these functions overlap, the thesis finds that community radio stations in Malawi concentrate more on the latter. The programming of the stations is influenced by the agendas of development agents who sponsor programmes thereby reducing opportunities for participation. However, although people's participation in the media is low or reduced, there are other ways in which through the media, people can benefit, enhance their capabilities and through which development agencies can reach their goals. The thesis argues that the radio stations fit well with an approach to development related to building capabilities (Sen, 1992) because they sometimes give people resources to enhance their capabilities and sometimes act as partners with development agencies and government, facilitating a variety of development goals. The thesis concludes that community radio in Malawi enables capabilities although very rarely through fully-fledged participation. 2015-06-29T15:05:50Z Pharmacological treatment of infantile nystagmus and assessing the impact from the patients perspective http://hdl.handle.net/2381/32446 Title: Pharmacological treatment of infantile nystagmus and assessing the impact from the patients perspective Authors: McLean, Rebecca Jane Abstract: Background : Nystagmus is an involuntary to and fro movement of the eyes that can be infantile or acquired and causes reduced vision. Little literature exists documenting how nystagmus affects quality of life and treatment options are largely empirical with very few randomised controlled trials. Methods : Semi-structured interviews of 21 participants were analysed using a constant comparison approach based upon grounded theory. A randomised, triple masked, controlled trial of gabapentin and memantine was performed on 66 participants with infantile nystagmus. Outcome measures were 25% improvement in visual acuity (primary outcome), 25% improvement in eye movement, absolute change in visual function and eye movement and descriptive analysis of nystagmus waveforms responding to treatment. Results : Analysis of participants' accounts revealed six domains of living that were adversely affected by nystagmus: visual function, restriction of movement (both physical and social), standing out/not fitting in, feelings about the inner self, negativity with regards to the future and relationships. Cosmetic appearance of nystagmus was, for the first time, described as being problematic and additional to other categories was an overarching and universal distress arising from nystagmus affecting every aspect of everyday life. Gabapentin and memantine did not improve visual function as a 25% improvement or when assessing the absolute differences. In contrast null region nystagmus intensity and NAFX were significantly different for treatment as gabapentin reduced intensity and improved NAFX by 25%. For absolute differences in null region nystagmus intensity gabapentin was also significant. Pendular waveforms prevalently appeared in those participants responding to gabapentin. Baseline measurements were often a predictor for success of treatment. Both gabapentin and memantine were both reasonably well tolerated. Conclusion : Interviews revealed universally negative experiences of living with nystagmus that are previously unreported. Gabapentin, and not memantine, significantly reduces eye movement in infantile nystagmus but does not improve visual function. 2015-06-29T14:54:19Z Testing the harmonisation and uniformity of the UNCITRAL model law on international commercial arbitration http://hdl.handle.net/2381/32445 Title: Testing the harmonisation and uniformity of the UNCITRAL model law on international commercial arbitration Authors: Lewis, Stewart Dean Abstract: The 1985 UNCITRAL Model Law attempts to introduce uniformity into the procedural aspects of international commercial arbitration and has been adopted by 97 jurisdictions. This thesis tests the achievement of this objective in Australia, Hong Kong and Singapore in respect of Article 34 (and its equivalent in the New York Convention on the Recognition and Enforcement of Foreign Arbitral Awards) which empowers a court to set aside an arbitral award. Uniformity in law is generally considered a matter of function and degree, with absolute uniformity not being required for the achievement of the appropriate degree of functional similarity. An internationalist approach to the interpretation of the Model Law is expressed in Article 2A, which was introduced in 2006, although this was required from the outset. The achievement of uniformity is tested by analysing how the legislators and courts have implemented (textual uniformity) and applied (applied uniformity) the Model Law. Significant textual dissimilarities are identified in how the three jurisdictions adopt an internationalist approach and some potentially significant textual dissimilarities in the adoption of Article 34/V. An analysis of over 300 cases shows, by reference to internationalist norms ('I-Norms'), that an internationalist approach has been present throughout, but in particular in the last 10 years or so in Singapore and the last 5 years in Australia. Applied uniformity is also tested by a method which identifies principles of law which pursuant to the internationalist approach are able to be cited cross border albeit not in a binding way ('I-Ratios' derived from International Ratio Decidendi). This analysis demonstrates numerous citations of decisions from other jurisdictions but few adoptions of their I-Ratios. The jurisdictions analysed are thus shown to have achieved what can be considered to be a constantly developing degree of textual and applied uniformity. 2015-06-29T14:43:35Z Improving population estimates using remotely sensed and ordnance survey datasets http://hdl.handle.net/2381/32443 Title: Improving population estimates using remotely sensed and ordnance survey datasets Authors: Kose, Mustafa Abstract: The accuracy of population data is of critical importance in supporting the design of public and private-sector facilities. Demographic data are usually supplied by national census organisations at pre-defined census output levels. However, demographic datasets may be required at user-defined spatial units that can be different from the initial census output levels. A number of population estimation techniques have been developed to address these problems. This thesis is one of those attempts aimed at improving small-area population estimates by using spatial disaggregation models of: 1) binary mapping, 2) address-weighted dasymetric and 3) volumetric estimation models. These interpolation approaches employs high-resolution aerial imagery, LiDAR-derived building volumes and the integration of building address points and occupancy information sourced from the Ordnance Survey © and Airbus Defence and Space. Census wards and output areas were used as source zones and target zones respectively, to estimate population counts in Leicester City and the Borough of Kensington and Chelsea, London where the population is distributed both horizontally and vertically. The predicted population values were compared with 2011 census of actual population datasets. Each method employed in the study generated different population estimates depending on their assumptions and required datasets. The accuracy appears to be mainly influenced by the type and quality of the ancillary datasets and also the interpolation method adopted. Based on the disaggregation models adopted in this study, the address-weighted model produced the best population estimates with Root Mean Square Error (RMSE) value of 0.64 and R2 score of 0.998 for the City of Leicester and RMSE value of 0.236 and R2 score of 0.997 for the Borough of Kensington and Chelsea. This estimation is an indication that building address point datasets that contain information on occupancy can be used within Dasymetric mapping approaches to improve population estimates over a range of urban areas. 2015-06-29T14:36:50Z Model Reductions in Biochemical Reaction Networks http://hdl.handle.net/2381/32442 Title: Model Reductions in Biochemical Reaction Networks Authors: Khoshnaw, Sarbaz Hamza Abdullah Abstract: Many complex kinetic models in the field of biochemical reactions contain a large number of species and reactions. These models often require a huge array of computational tools to analyse. Techniques of model reduction, which arise in various theoretical and practical applications in systems biology, represent key critical elements (variables and parameters) and substructures of the original system. This thesis aims to study methods of model reduction for biochemical reaction networks. It has three goals related to techniques of model reduction. The primary goal provides analytical approximate solutions of such models. In order to have this set of solutions, we propose an algorithm based on the Duhamel iterates. This algorithm is an explicit formula that can be studied in detail for wide regions of concentrations for optimization and parameter identification purposes. Another goal is to simplify high dimensional models to smaller sizes in which the dynamics of original models and reduced models should be similar. Therefore, we have developed some techniques of model reduction such as geometric singular perturbation method for slow and fast subsystems, and entropy production analysis for identifying non–important reactions. The suggested techniques can be applied to some models in systems biology including enzymatic reactions, elongation factors EF–Tu and EF–Ts signalling pathways, and nuclear receptor signalling. Calculating the value of deviation at each reduction stage helps to check that the approximation of concentrations is still within the allowable limits. The final goal is to identify critical model parameters and variables for reduced models. We study the methods of local sensitivity in order to find the critical model elements. The results are obtained in numerical simulations based on Systems Biology Toolbox (SBToolbox) and SimBiology Toolbox for Matlab. The simplified models would be accurate, robust, and easily applied by biologists for various purposes such as reproducing biological data and functions for the full models. 2015-06-29T14:29:24Z Factors influencing implementation of an enhanced recovery programme in colorectal surgery http://hdl.handle.net/2381/32441 Title: Factors influencing implementation of an enhanced recovery programme in colorectal surgery Authors: Ihedioha, Ugochukwu Chima Abstract: Introduction: Major recent advances in modern surgery have focussed on processes and pathways relating to perioperative recovery. Optimising patients perioperatively is essential in improving outcomes. The enhanced recovery programme is an integrated pathway that combines evidence based practice in a synergistic manner to improve outcomes. This research concerns perioperative recovery for patients undergoing major abdominal surgery. Aim: The aim of this study was to investigate the factors that influence the implementation of an enhanced recovery programme in patients undergoing elective colorectal surgery. Method: The study was done in four phases. The first phase was to assess the feasibility of introducing fast track surgery in our unit by recruiting patients undergoing reversal of loop ileostomy so as to reduce hospital stay. The second phase, compared laparoscopic colorectal surgery with open colorectal surgery with regards to hospital stay and complication rates. Both groups of patients were followed up over a two year period to compare incisional hernia rates. The third phase, compared the use of video education in the psychological preparation of patients undergoing elective colorectal resection with information leaflets and verbal information. The fourth phase, compared short term outcomes between patients undergoing elective colorectal resection early in the week(Monday to Wednesday) with those later in the week(Thursday to Friday). Results: Early discharge is safe and achievable following reversal of loop ileostomy. Laparoscopic surgery does not improve short term outcomes following colorectal surgery compared with open surgery. Long term outcomes (incisional hernia rates) are similar. Supplementing video education with oral and written information prepares patients better psychologically for surgery although it does not improve short term outcomes. Operating on patients earlier in the week improves short term outcomes. Conclusion: The enhanced recovery programme is feasible and safe and should be practiced by individual units offering colorectal surgery. Patients benefit from preconditioning using video education and being operated upon early in the week 2015-06-29T14:22:55Z Urban Planning and the Motor Car, 1955-1977: Responses to the growth of private motoring in Leicester and Milton Keynes http://hdl.handle.net/2381/32440 Title: Urban Planning and the Motor Car, 1955-1977: Responses to the growth of private motoring in Leicester and Milton Keynes Authors: Harrison, Richard Simon Abstract: This thesis examines the response of British urban planners to the rise of private motoring in the 1950s, 1960s and 1970s. The examination begins with an exploration of important planning documents and events of the 1950s and 1960s, relating to the issue of rising car ownership. It is followed by an exploration of the response of urban planners to rising car ownership in Leicester and Milton Keynes. This research covers an important stage in the rise of car culture in Britain and an important stage in the evolution of urban planning. From 1950 to 1960, the number of cars on Britain's roads rose nearly two-and-a-half times to 5.5 million, which was seen as the beginning of mass car ownership. Although this prospect was often welcomed as a sign of affluence, it was also deemed to require a robust response from physical planners to prevent widespread traffic congestion and environmental nuisance. In this thesis I make four arguments. I argue, firstly, that it was in the 1950s and 1960s that a durable framework for approaching questions of urban transport in a motorised Britain was first worked out. Secondly, the prospect of motorisation posed fresh questions about the type of urban society that planning should be employed to support. The planners elected to encourage automobility and consumerism, but were also obliged to give more recognition to the importance of building conservation, urban environmental quality, and public transport. Thirdly, urban planners were directed by a powerful set of economic and social forces to plan in the car's favour. Fourthly and finally, I argue that the decision to accommodate motorisation helped to provoke a backlash against sweeping redevelopment and top-down planning that altered planners' relationship with the public, giving rise to a greater appreciation for the value of the existing urban fabric. 2015-06-29T13:58:19Z Superfluid helium droplets: from spectroscopy to magnetic nanoparticles http://hdl.handle.net/2381/32439 Title: Superfluid helium droplets: from spectroscopy to magnetic nanoparticles Authors: Feng, Cheng Abstract: This project applies superfluid helium droplets in two big areas: spectroscopy and nanoparticles formation. Helium droplets, consisted of more than 103 helium atoms, provide a non-friction and very cold (~0.37 K) environment for clusters/nanoparticles growth, which offers unique advantages as a medium in applications of both spectroscopy and nanostructures formation. By sequentially adding NaCl and water molecules, the dissolution process of NaCl in water can be experimentally studied for the first time. This is achieved by recording the infra-red spectra of NaCl(H2O)n (1 ≤ n ≤ 7) complexes in O-H stretching region in combination with ab initio calculations. In particular, two bands have been assigned to dissolution of NaCl in water. The existence of quantum vortices in helium droplets has been firmly evident from spherical Ag nanoparticles formed in a chain. Quantum vortices provide a new route for the formation of one-dimensional nanostructures, which has been exploited in the fabrication of novel nanowires. Finally the pioneering work on the fabrication of both antiferromagnetic and ferromagnetic nanomaterials is reported for the first time, taking Cr and Ni as examples respectively. It is found that we can force ferromagnetic ordering in magnetic materials in superfluid helium. In particular, antiferromagnetic chromium has been discovered to convert to ferromagnetic, and the magnetism of ferromagnetic materials can have hugely enhanced magnetic moments that are close to the theoretical limit. This will have potential for applications in biomedical science, data storage and energy efficient technologies in the longer term. 2015-06-29T13:50:04Z The role of Birkeland currents in the Dungey cycle http://hdl.handle.net/2381/32438 Title: The role of Birkeland currents in the Dungey cycle Authors: Coxon, John Charles Abstract: The interaction of the solar wind with the near-Earth environment forms Earth's magnetosphere and drives a process called the Dungey Cycle. Birkeland currents are required to transmit stress within the system. This thesis uses large-scale, statistical analysis (both temporal and spatial) to examine their magnitude and spatial extent in the context of the Dungey Cycle. Active Magnetosphere and Planetary Electrodynamics Response Experiment (AMPERE) data are processed; the methodology is described and the success rate examined before the regions 1 and 2 Birkeland current magnitudes are explicitly compared to dayside and nightside reconnection rate for the first time. The magnitudes of the currents are well-correlated with both, suggesting that magnetic reconnection on day and nightside is driving higher Birkeland current magnitudes. The behaviour of the R1 and R2 currents is examined in a superposed epoch analysis of 2900 substorms identified by SuperMAG. Both current systems increase in magnitude and spatial extent during the growth phase of a substorm, peaking shortly after expansion phase onset. This analysis yields new information about how the currents react to the substorm cycle. A seasonal and a diurnal variation in the Birkeland current magnitudes is described and linked to the effect of ionospheric conductance; this is explored further, and it is found that currents are well-described by multiplying the dayside reconnection rate by an number representing the global variation of conductance with UT. This thesis presents evidence that Birkeland current magnitudes are consistent with driving by ionospheric convection, which is in turn driven by magnetic reconnection on both the dayside and the nightside. It is also demonstrated that the current ovals measured by AMPERE expand and contract with magnetic reconnection as open flux is added to and removed from the polar cap. These insights are expanded upon with ideas for future research. 2015-06-29T12:17:40Z The effectiveness of the EU race equality directive at national level. A comparative study of British and Spanish legislation and policies http://hdl.handle.net/2381/32437 Title: The effectiveness of the EU race equality directive at national level. A comparative study of British and Spanish legislation and policies Authors: Benedi Lahuerta, Sara Abstract: The EU Race Equality Directive (RED) was adopted in 2000 to foster the development of a basic legal framework to address racism and, more generally, to put into effect the principle of equal treatment at national level. However, there are some concerns that the effects of the RED have not been as far-reaching as expected. Through a comparative study between Britain and Spain, this thesis analyses whether the RED has triggered effective legislation and policies in these jurisdictions, and which factors and actors may be relevant to improve the effectiveness of racial equality legislation and policies. Initially, the thesis acknowledges that the RED's potential to trigger effective regulatory strategies at national level is constrained by its underlying enforcement model, based mainly on individual litigation. Building upon the theory of the Social Working of Law, the concept of effectiveness is defined as the combination of 'ex-ante effectiveness', which contributes to preventing discrimination, and 'ex-post effectiveness', which minimises the negative effects that discrimination has on victims, once it has occured. This distinction is used to frame the comparative analysis, which is conducted in three building blocks. Firstly, it is argued that formal adjudication has intrinsic limitations because victims bear the burden to initiate legal proceedings but, at the same time, the system deters them from doing so. Secondly, it is submitted that a diverse network of advice-providers (ie equality bodies, trade unions and NGOs) and an appropriate use of Alternative Dispute Resolution mechanisms can contribute to improving ex-post effectiveness. Finally, this thesis also recognises the importance that employers' policies can have in preventing discrimination, such as those derived from positive duties, collective bargaining and voluntary initiatives. However, the thesis also concedes that the effectiveness of employers' policies largely depends on the regulatory framework, social awareness about racial discrimination and workforce participation. 2015-06-29T12:03:36Z Spaceborne doppler radars in convection: performance of EarthCARE and beyond http://hdl.handle.net/2381/32436 Title: Spaceborne doppler radars in convection: performance of EarthCARE and beyond Authors: Augustynek, Tomasz Michal Abstract: The thesis concerns the assessment of the performance of the upcoming Earth Cloud Aerosols Radiation Explorer (EarthCARE) Doppler cloud profiling radar in convection. Spaceborne Doppler radar data are simulated starting from high-resolution CRM model data, through forward Monte Carlo simulation from which the voltage signals as sampled by specific radar configuration are generated. Until the launch of Earth- CARE in 2016, simulations are the only means of assessing the impact of EarthCAREs configuration on the accuracy of the Doppler products (reflectivity and mean Doppler velocity). Two of the main contributors to EC-CPR total error budget are the multiple scattering and non-uniform beam filling effect errors, which can be mitigated using methods described in the thesis. However, for Earth- CARE radar using the conventional pulse pair technique, the scientific requirement for accuracy of 1 m/s at 1 km integration of Doppler velocity cannot be met for deep convective systems, even if the correction methods are applied. The thesis then focuses on six polarization diversity radar systems, three for W-band (94 GHz) and three for Ka-band (35 GHz). After the correction methods are applied for MS and NUBF effects, the accuracy of 1 m/s for 500 m integration is possible for all W-band configurations assessed. This includes relatively small antennas of 2.5 m currently being implemented in space. Consequently, two key results for measurements in deep convection can be drawn for future radar concept design. Firstly, the large antenna will help to minimize the effects of non-uniform beam filling and multiple scattering. Secondly, the polarization diversity can solve the problem of aliasing of velocities. 2015-06-29T11:48:14Z DNA methylation, genomic imprinting and polyphenism in the bumblebee, Bombus terrestris http://hdl.handle.net/2381/32434 Title: DNA methylation, genomic imprinting and polyphenism in the bumblebee, Bombus terrestris Authors: Amarasinghe Kankanamge, Harindra Eranthi Abstract: Genomic imprinting, the parent-of-origin specific expression of alleles is an important area of research in evolutionary biology and human health (cancers and developmental syndromes). Haig's kinship theory suggests that the maternally and paternally derived alleles of offspring resource allocation genes have evolved under different selectional pressures. Thus within different kin related individuals they are expressed unequally, each allele favouring their own inclusive fitness. Social insects provide the best independent model system to study the evolution of imprinting. However, imprinting has not been discovered in any social insect. My PhD lays the groundwork for a social insect model of genomic imprinting. Methylation is a common epigenetic tag of genomic imprinting in mammals and flowering plants. I found that a functional methylation system which is involved in the reproductive caste formation, development and social behaviour is present in the bumblebee, Bombus terrestris. Under queenless conditions, reproducing and non-reproducing worker castes show different brain methylome patterns. Alteration of methylation can cause a sterile worker to turn into a reproductive worker with increased aggressive behaviour and ovary development. Next I found monoallelic methylation associated with monoallelic expression in genes predicted to be imprinted by Haig's theory. Also, differential allele specific expression that are apparently due to parent-of-origin effects is present in reproduction loci of B. terrestris. Reciprocal crosses at these loci is recommended as further work, to check whether these expression patterns are due to genomic imprinting. I assess the effects of maternally and paternally contributed sociobiological factors on worker male production and found that the paternity or the queen mating frequency has a significant influence on worker male production in eusocial Hymenoptera. Finally, I also studied the polyphenism involved in phase dependent behavioural plasticity of locusts. I found that the transition of solitarious to fully gregarious behaviour in the desert locust, Schistocerca gregaria begins without significant changes in the DNA methylation landscape of the CNS but subjected to the pronounced differences at a later stage. 2015-06-29T11:41:32Z Natural variation within a clock gene of Drosophila melanogaster : a phenotypic and molecular analysis http://hdl.handle.net/2381/32429 Title: Natural variation within a clock gene of Drosophila melanogaster : a phenotypic and molecular analysis Authors: Sawyer, Lesley Anne Abstract: The clock gene period encodes a repetitive series of Threonine-Glycine (Thr-Gly) pairs in D. melanogaster. This sequence is polymorphic in length and shows a clinal distribution in Europe, whereby the shorter length variants are more frequent in warmer regions and the longer ones in colder areas. A series of new correlations performed with the European population data suggests that thermal selection may be a factor in generating the cline. DNA sequence analysis of various Thr-Gly haplotypes supports a model where the (Thr-Gly)2o and (Thr-Gly)23 alleles are considered as ancestral, since all variants can be derived from them. A reciprocal cline is observed for the (Thr-Glyho length valiant in eastern Australia, suggesting that selection may be maintaining the polymorphism, and a further correlation of temperature with allele frequency suggests, as in European populations, that the cline may be thermally mediated. However, the other major allele the (Thr-Gly)17 was spatially homogenous. The temperature compensation of the clock was examined by investigating the freerunning locomotor activity cycles of different natural ThrGly length variants from Europe and Australia. A relationship between Thr-Gly length and temperature compensation which could help explain the continental spatial differences was observed. Locomotor activity profiles in light/dark cycles were also examined in the European variants, and revealed subtle phenotypic differences between the Thr-Gly length variants that could also contribute to the observed clinal patterns. The energy expenditure of different Thr-Gly length variants was also measured and revealed behavioural adaptations for possible fitness advantages. Throughout the behavioural analyses there was also evidence that the structural (Thr-Gly)3 motif played an important role in the temperature compensation mechanism and energy expenditure of the fly. 2015-06-26T14:23:37Z Government and society in Tudor and Stewart Norwich, 1525 – 1675 http://hdl.handle.net/2381/32378 Title: Government and society in Tudor and Stewart Norwich, 1525 – 1675 Authors: Pound, John F. 2015-06-17T12:41:22Z Molecular analysis of circulating cell-free DNA in breast cancer patients http://hdl.handle.net/2381/32369 Title: Molecular analysis of circulating cell-free DNA in breast cancer patients Authors: Blighe, Kevin Anthony Abstract: Identifying disease-related variants is a primary aim of human genetics. In breast cancer, loss of heterozygosity at specific loci was previously demonstrated in paired tumour and circulating plasma cell-free DNA (cfDNA) samples. However, alterations unique to cfDNA were also found in all cases, suggesting disease progression. These results prompted the characterisation of the circulating breast cancer genome in more detail in this thesis, to test the hypothesis that cfDNA acts as a surrogate tumour marker. This was achieved using Affymetrix SNP 6.0 technology and bioinformatics to map SNP and copy number variation (CNV), comparing cfDNA with matched normal lymphocyte and tumour DNA in 65 breast cancer patients and 8 healthy female controls. Results in this thesis show that comparison of cfDNA SNP genotypes can distinguish between primary breast cancer patients and healthy controls (p<0.0001), and between pre-surgical breast cancer patients and those who already had surgery/treatment (p=0.0016). A significant difference (p=0.0006) was also found between cfDNA samples taken an average of 3 years apart in women on follow-up, again suggesting progression. In addition, CNV amplification was observed in matched tumour and cfDNA at numerous loci on different chromosome arms. Many of these tumour-specific CNVs contributed significantly to disease through logistic regression analysis and remained detectable in cfDNA up to 12 years after diagnosis despite no other evidence of disease. This finding strongly infers breast cancer dormancy in the majority of patients on follow-up. In addition, candidate CNVs were validated by real-time qPCR and additional bioinformatics revealed key SNP and CNV signatures of breast cancer patients. If validated in other patient series, the results could alter the diagnostic and prognostic 2015-06-11T09:00:48Z Thrift and the value of scarce resources: A circuit of culture approach to the production, representation and consumption of the cultural value of thrift through the lens of food magazines http://hdl.handle.net/2381/32361 Title: Thrift and the value of scarce resources: A circuit of culture approach to the production, representation and consumption of the cultural value of thrift through the lens of food magazines Authors: Cole, Jennifer Marie Abstract: Food media in the UK has grown in popularity, even during the recent recession; at the same time, the recession made thrift a fashionable topic in the public sphere and popular culture. The thesis investigates how the cultural value of thrift is constructed in the context of food magazines. The thesis employs a multi-method 'circuit of culture' approach in order to more adequately assess the producer-text-consumer relationship than is typical in magazines studies. In doing so, the thesis both generates a case study of how the cultural value of thrift is produced, represented and consumed through food magazines, and examines and contextualises the roles of different market actors within the circuit, including both cultural intermediaries (magazine writers) and readers. The findings demonstrate that thrift is a relational and negotiated concept. The textual analysis of the magazines demonstrates how both time and money are positioned as valuable resources within the magazines. Magazines act as manuals on resource management by offering thrift related advice on a number of issues including when to invest more or less time/ money in food preparation, and practices to reduce waste, in order to demonstrate how food work can be achieved within the constraints of everyday life. In the case of magazine writers and readers, findings reveal how thrift is defined through resource management: thrift is constructed through notions of scarcity and the associated valuing of time and money as resources. As such, individuals' understandings of thrift—in relation to necessities, competing demands and shifting proximities to scarcity— are primarily shaped by gender (especially feminine norms around motherhood and domestic labour); and, for cultural intermediaries, genre and professional conventions. Finally, the analysis assesses the usefulness of the circuit of culture approach to studies of cultural values and cultural products. 2015-06-08T13:42:16Z Remote sensing of spatiotemporal phytoplankton dynamics of the optically complex Lake Balaton http://hdl.handle.net/2381/32360 Title: Remote sensing of spatiotemporal phytoplankton dynamics of the optically complex Lake Balaton Authors: Palmer, Stephanie Catherine Jane Abstract: This thesis explores the use of remote sensing to measure the phytoplankton biomass of Lake Balaton, Hungary via the proxy pigment, chlorophyll-a (chl-a). Several scales of spatial and temporal variability are considered, using a ten year time series of Medium Resolution Imaging Spectrometer (MERIS) satellite imagery, ship-mounted Light Detection and Ranging (LiDAR), and water sampling and laboratory measurements from punctual and ongoing campaigns. Existing remote sensing methods are adapted to Lake Balaton for the first time, and novel directions are demonstrated which may be applied to other lakes in the future. Several chl-a retrieval algorithms applied to archive MERIS data are calibrated and validated using an extensive dataset of coinciding in situ measurements and results from each are compared. The application of two atmospheric correction algorithms is also validated and their influence on chl-a retrieval is considered in comparison with the use of un- atmospherically corrected, top-of-Atmosphere (TOA) data. The fluorescence line height (FLH) algorithm applied to TOA MERIS data is found to accurately and robustly retrieve Lake Balaton chl-a (R2 = 0.87; RMSE = 4.19 mg m-3), particularly during high biomass bloom events (chl-a ≥ 10 mg m-3). This algorithm is then applied to the full MERIS archive (2002-2012), resulting chl-a time series are smoothed at the pixel level, and phytoplankton phenology metrics are extracted and mapped. Phenology metric mapping in lakes using MERIS remote sensing is demonstrated and significant spatiotemporal variability in bloom metrics is apparent. Laboratory tank and in situ ship-mounted Ultraviolet Fluorescence LiDAR (UFL) measurements indicate another novel direction for lake remote sensing. Chl-a, as well as total suspended matter (TSM) and coloured dissolved organic matter (CDOM), were measured and cyanobacteria was distinguished from chlorophyta via fluorescence emission spectra. The feasibility of retrieving accurate and quantitative information on Lake Balaton phytoplankton biomass dynamics through the use of remote sensing techniques is confirmed, and the resulting added value for both science and management is highlighted. 2015-06-08T13:37:05Z Studies on transcriptional regulation of pyruvate formate lyase in Streptococcus pneumoniae http://hdl.handle.net/2381/32357 Title: Studies on transcriptional regulation of pyruvate formate lyase in Streptococcus pneumoniae Authors: Younis, Firas Abbas Abstract: In the nasopharynx, Streptococcus pneumoniae relies on mucin glycoproteins, which are rich in galactose. Galactose stimulates mixed-acid fermentation in S. pneumoniae. Pyruvate formate lyase (PFL) is a key enzyme in mixed-acid fermentation, and its inactivation attenuates pneumococcal virulence, and abolishes mixed-acid fermentation. Limited information is available on the transcriptional regulation of pflA, which codes for pyruvate formate lyase activating enzyme (PFL-AE) and post-translationally activates inactive PFL, and pflB, both required for active PFL. Through analysis of a strain mutated in pflB by microarray, six transcriptional regulators potentially involved in the regulation of pflB were identified. Inactivation of these transcriptional regulators led to decreased growth in the presence of glucose or galactose, and an altered profile of fermentation end products. Using different experimental techniques such as electrophoretic mobility shift assay, and transcriptional lacZ-fusions, three transcriptional regulators were found to be directly controlling the transcription of pflA or pflB. The results show that the catabolite control protein A (CcpA) plays an activating role in pflB regulation in the presence of galactose, whereas the transcriptional regulators MerR2 and GntR repress the transcription of pflB. Moreover, CcpA and MerR2 were determined as the transcriptional repressors of pflA. It was also found that MerR2 contributes to the regulation of ccpA, and that MerR2 and CcpA interact for regulation of pflA and pflB. The activating role of CcpA and MerR2 in the regulation of PlcR, regulator of virulence genes in Bacillus spp., was also determined. Transcriptional lacZ-fusions to the promoters of the transcriptional regulators CcpA, MerR2, and PlcR showed high induction in host-derived sugars such as galactose, glucose, mannose, and N-acetylglucosamine. Loss of CcpA and/or MerR2 had a significant impact on pneumococcal virulence and colonisation in a mouse model of pneumococcal infection. 2015-06-05T13:08:22Z Treatment of metastatic colorectal cancer : A role for Curcumin? http://hdl.handle.net/2381/32351 Title: Treatment of metastatic colorectal cancer : A role for Curcumin? Authors: James, Mark Ian Abstract: Colorectal cancer remains the third largest cause of mortality from cancer related death, with approximately 90% of these deaths attributed to metastatic spread of the disease. There is a need to improve chemotherapy, with the dietary polyphenol curcumin, derived from turmeric, representing a potential candidate as it possess very few side effects and it has shown efficacy in mouse models. Recent advances in our understanding of tumour development have highlighted the existence of tumour initiating cells (TIC), which possess clonogenic potential, are essential for tumour growth, and represent an important therapeutic target. This study sought to determine whether curcumin in combination with oxaliplatin+5-Fluorouracil (OX+5-FU) represented a better combination for targeting TICs, using a variety of models consisting of cells derived directly from colorectal liver metastasis (CRLM). ALDHHigh activity, CD133 and CD26 were all found to mark a spheroid forming population, a method that tests for clonogenicity and selects for TICs. Curcumin significantly reduced the number of spheroids compared to DMSO, and enhanced efficacy of OX+5-FU. The only marker to decrease after treatment was ALDHHigh activity, which was also positively associated with spheroid growth. CD26 expressing cells were identified as a possible chemo-resistant population, however, this population remained unaffected by curcumin. Ex vivo analysis using explant cultures demonstrated that curcumin could significantly decrease ki67 and increase cleaved capase-3 expression, notably enhancing the effects of oxaliplatin in a proportion of patients. A pilot study was undertaken using non-obese diabetic/severe combined immunodeficient (NOD-SCID) mice to reflect a clinical regimen, and assess in vivo whether curcumin could enhance efficacy of OX+5-FU, but the results advocate the use of higher doses as little effect was seen. Overall this body of work contributes to knowledge on propagating CRLM TICs, their expression of known TIC markers, and response to curcumin. 2015-06-04T10:17:16Z Applying Schelling's Dynamic Models of Segregation to Psychological Decision Making http://hdl.handle.net/2381/32350 Title: Applying Schelling's Dynamic Models of Segregation to Psychological Decision Making Authors: Kastyak, Beata Maria Abstract: Agent-Based Models (ABM) have become accepted as an experimental technique in social psychology research. However, ABMs are rarely validated externally. This research attempted to experimentally validate, in particular the Schelling's Dynamic Models of segregation. This model is an agent-based proximity model implemented with a new parameter, the tolerance level, which is based on perceived similarities of the agents. The introduction of this new parameter has made ABM applicable to social sciences. Five parameters (tolerance threshold, neighbourhood ranges, environment types, group size and proportions) of the model have been chosen to be tested experimentally and evaluated theoretically. Therefore, relevant chapters include an experimental and a theoretical section. In the experimental part group of participants played the linear public good game with altruistic punishment. The level of cooperation was measured through contributions scores. In the theoretical part the outcome of the simulation models was evaluated using the segregation factor. The experimental results and the simulation outcomes have been compared in each chapter separately. Five chapters inspected the five parameters of the Schelling model considering additional prospects. The tolerance threshold was tested using groups with different wealth origin. The neighbourhood ranges were tested using groups with different geographical proximities. The environment type parameter was tested using different gender groups. The group sizes parameter was tested using different community sizes. Finally the group proportions were tested by allocating the participants into groups with different ethnicity proportions. Additionally, the effects of these conditions were examined on altruistic punishment. The findings show that the contributions scores alter between the different scenarios. However, altruistic punishment is not always influenced. This thesis provides a partial validation of five parameters of the Schelling model and contributes to an effective development of all future ABMs. The research suggests unique recommendations for further research in both the experimental and theoretical parts. 2015-06-04T10:09:55Z Managing the Morbidity Related to Flap Reconstruction in Major Maxillofacial Oncology Surgery http://hdl.handle.net/2381/32343 Title: Managing the Morbidity Related to Flap Reconstruction in Major Maxillofacial Oncology Surgery Authors: Avery, Christopher Martin Edward Abstract: There is substantial systemic and local morbidity associated with complex reconstruction of the maxillofacial (face, mouth, jaws and neck) region and the distant donor site of the free flap used to reconstruct the defect. This morbidity may be alleviated by careful patient preparation, selection of operation, improving wound care and new surgical procedures. Many aspects of morbidity are not readily amenable to investigation because of a multitude of confounding clinical factors. Improvements in the quality of care may be obtained by careful evaluation of outcomes and comparison with the literature. This body of work represents a reflection on my surgical practice, animal experimental studies and computer modelling techniques which have reduced morbidity and improved my ability to counsel patients. Major elements include the techniques of suprafascial dissection of the soft tissue radial flap and prophylactic internal fixation of the osteocutaneous radial donor site which have become increasingly accepted within the United Kingdom and overseas. The impact of differing flap choice, particularly in the medically compromised group, has been considered. The quality of the clinical documentation has been improved. Biomechanical issues raised by the clinical studies were investigated in laboratory work using the sheep tibia model of the human radius. A computer based model of the sheep tibia, created using a finite element analysis technique, was validated against the preceding biomechanical studies. This simulation was used to investigate the most effective design of osteotomy cuts and type of plate for reinforcement of a straight osteotomised bone, such as the radius, or segmental defects of the mandible. Interest in my work is reflected in the high rate of presentations at the Annual Scientific Meetings of the British Association of Oral & Maxillofacial Surgery combined with the joint second highest rate of successful conversion to publication in the United Kingdom. Description: Thesis Submitted for the Degree of Doctor of Medicine by Published Work University of Leicester 2015-06-02T15:35:50Z Microparticles as biomarkers of early changes leading to cardiovascular disease in chronic kidney disease http://hdl.handle.net/2381/32342 Title: Microparticles as biomarkers of early changes leading to cardiovascular disease in chronic kidney disease Authors: Abbasian, Nima Abstract: Hyperphosphataemia in patients with advanced chronic kidney disease (CKD) is thought to be an important contributor to cardiovascular risk, in part because of endothelial cell (EC) dysfunction induced by inorganic phosphate (Pi). Such patients also have an elevated circulating concentration of pro-coagulant endothelial microparticles (MPs), leading to a pro-thrombotic state, which may contribute to acute occlusive events. It is hypothesised that hyperphosphataemia leads to MP formation from ECs via an elevation of intracellular Pi, which directly inhibits phosphoprotein phosphatases, triggering a global increase in phosphorylation and cytoskeletal changes. Using cultured human endothelial cells (EAhy926), incubation with elevated extracellular Pi (2.5mM) led to a rise in intracellular Pi concentration within 90min. This was mediated by PiT-1/slc20a1 Pi transporters; and led to global accumulation of Tyr- and Ser-Thr phosphorylated proteins, a marked increase in cellular Tropomyosin-3, plasma membrane blebbing and release of 0.1 – 1 micron diameter MPs. The effect of Pi was independent of oxidative stress or apoptosis. Similarly, global inhibition of phosphoprotein phosphatases with orthovandate or fluoride also yielded a global protein phosphorylation response and rapid release of MPs. The Pi-induced MPs expressed VE-cadherin and superficial phosphatidylserine, and in a thrombin generation assay were significantly more pro-coagulant than particles derived from cells incubated in medium with a physiological level of Pi (1mM). These data demonstrate a mechanism of Pi-induced cellular stress and signalling which may be widely applicable in mammalian cells; and in ECs provides a novel pathological link between hyperphosphataemia, generation of MPs and thrombotic risk. 2015-06-02T13:33:28Z Facilitative secularism: the place of religious arguments in public political debate http://hdl.handle.net/2381/32341 Title: Facilitative secularism: the place of religious arguments in public political debate Authors: Alkan, Yavuz Selim Abstract: The predominant understanding of secularism is based on two notions. First, the secular state should be completely or strictly separated from religion. Second, the secular state should be strictly neutral with regard to religion. This understanding of secularism, what I call secularism as strict separation/neutrality, equates neutral to secular and excludes religious arguments a priori from public political debate by invoking secular or public reason. Its more aggressive form, viz. ethical secularism, embraces the whole secularisation thesis as a comprehensive doctrine and thereby aims to impose a secular way of life upon individuals. Both types of secularism have significant exclusionary effects on religious arguments. They are therefore inconsistent with the democratic ideals of equal participation and state neutrality. In order to address this problem, I suggest in this thesis the need to reconsider the relationship between secularism and the place of religious arguments in public political debate. The originality in the thesis lies in its redefinition of this relationship within the context of an alternative understanding of secularism. I argue that the democratic principles of equal participation and state neutrality are best pursued when a facilitative understanding of secularism is embraced. Facilitative secularism is based on three assumptions. First, that there should be a minimum functional, institutional, organisational, and role differentiation between the state and religion, what I call secularism as minimal differentiation. Second, that secularism as minimal differentiation should be delinked from the restrictive interpretations of philosophical and sociological secularisation. And third, that a more inclusive and pluralist framework for public political debate should be generated. This framework should be created by redefining the doctrine of restraint. The place of both religious and secular arguments in public political debate should be determined according to whether they comply, not with secular or public reason, but with the normative criteria of secularism as minimal differentiation and the civic virtues of deliberation. In this study, I also apply this novel understanding of secularism to an illustrative example of the Turkish experience of secularism. The aim is to indicate how well facilitative secularism provides a suitable theoretical and normative framework with respect to expression of religious arguments in public political debate in Turkey. 2015-06-02T13:26:34Z Determinants of capital structure in Asian firms: new evidence on the role of firm level factors, industry characteristics, and institutions http://hdl.handle.net/2381/32340 Title: Determinants of capital structure in Asian firms: new evidence on the role of firm level factors, industry characteristics, and institutions Authors: Cheng, Hang Abstract: This thesis investigates the determinants of capital structure in Asian countries. The aim is to provide new evidence on the role of firm's specific factors, industry characteristics and institutions on firms' capital structure decision. The Asian markets have significantly benefitted from economic expansion and have experienced a series of financial system reforms in the recent decades. The rapid growth attained by the Asian economies, was also accompanied by periods of financial turmoil. These factors collectively call for investigating the factors affecting the decision of capital structure particularly in the last decade. The study thus provides new empirical evidence on the determinants of capital structure in Asia during the period 2006-2011. The result reveals that financing patterns of firms can be driven by their own firm characteristics, industry nature, general economic condition and institutional attributes. Firstly, profitability, administration expenses, firm size, firm liquidity, market-to-book ratio have shown significant association to firm's capital structure decision in Asia. There empirical evidence supports the existence of dynamic capital structure, which is in line with trade-off theory. During the recent financial crisis (2008-2009), the results show no evidence of adjustment to target capital by Asian firms. In general, the firm-specific factors have a more powerful explanation on firm's financing decisions in mature industries compared to growing industries. In particular, firms from technology or healthcare sectors, most of these types of firms are still young and at start-up stage in Asia and they hardly rely on debt finance with lesser credit record, higher R&D expenses, higher risk and more future uncertainties. The institutional and macroeconomic factors have a more significant impact on a firm's long-term financing decision compared short-term financial decision. In Asia, the firms tend to excessively rely on short-term debt to meet long-term financing requirement under a weaker institutional environment. 2015-06-02T13:19:43Z Structural investigation of the STAR protein Sam68 http://hdl.handle.net/2381/32338 Title: Structural investigation of the STAR protein Sam68 Authors: Foot, Jaelle Nicola Abstract: Sam68 is a member of the STAR family of proteins, linking post-transcriptional gene regulation with signal transduction pathways. Sam68 has been shown to specifically regulate the alternative splicing of many genes through interactions with the pre-mRNA and spliceosomal machinery. Selection of particular isoforms of several of these genes has been shown to contribute to neoplastic transformation and aberrant Sam68 expression and function has been implicated in the development of various genetic diseases and cancers. It is therefore important to understand Sam68 RNA recognition at the molecular level in order to design next generation drug therapies. This thesis describes the structural and biophysical techniques used to define the bipartite RNA consensus sequence specifically recognised by Sam68 and the mechanisms of interaction. This data provides a model of Sam68 contribution to alternative splicing regulation. Splice site selection is also influenced by posttranslational modifications of Sam68 including serine and threonine phosphorylation. In several cases, the phosphorylation state of Sam68 directly influences the outcome of splicing and leads to cancer development. Identification of phosphorylation sites in the STAR domain of Sam68 by NMR and radiolabelled kinase assays reveals how this post-translational modification may affect RNA binding at the molecular level. 2015-06-02T13:04:52Z Electrochemistry and galvanic deposition of group 10 & 11 transition metals using deep eutectic solvents http://hdl.handle.net/2381/32337 Title: Electrochemistry and galvanic deposition of group 10 & 11 transition metals using deep eutectic solvents Authors: Forrest, Gregory Charles Hereward Abstract: The galvanic deposition of metals has wide ranging applications in many industries. One example is the printed circuit board industry, where galvanic coatings are used as both a catalyst for the activation of the surface of a substrate and protective coating to prevent the oxidation of the surface. Deep Eutectic Solvents (DESs) have received growing interest in the area of metal processing, due to the unique solvation properties and ability to dissolve metal salts, without the need for addition of acids or bases. The DESs have been widely applied in electrochemical processes, where electrochemistry can be performed without the need for addition of an electrolyte. In this work, the speciation of the group 10 and 11 metals has been characterised using UV – Vis spectroscopy. The electrochemistry of the group 10 and 11 elements has been characterised using cyclic and linear sweep voltammetry and related to the speciation of the metal centres. Further characterisation of the electrochemistry was performed using an electrochemical quartz crystal microbalance, allowing for the rate and current efficiency of the electrochemical reaction to be measured. Galvanically deposited coating of group 10 and 11 metals, were produced on a standardised copper substrate. The morphology of the coatings was characterised by atomic force (AFM) and scanning electron microscopy (SEM) and the composition by energy dispersive X – ray (EDX) and X – ray photoelectron spectroscopy (XPS). The mechanism by which the galvanic coatings are formed was probed. The reaction mechanism was predicted from the formal electrode potential of the metal redox couples. The predicted mechanisms were experimentally investigated using quartz crystal microbalance experiments. The quartz crystal microbalance also allowed for the determination of the rate of the galvanic reactions. 2015-06-02T11:08:03Z A randomised control trial investigating the effects of parenteral fish oil on survival outcomes in critically ill patients with sepsis http://hdl.handle.net/2381/32336 Title: A randomised control trial investigating the effects of parenteral fish oil on survival outcomes in critically ill patients with sepsis Authors: Hall, Thomas Charles Abstract: Introduction: Sepsis is a leading cause of mortality in critically ill patients on the intensive care unit (ITU). Death from sepsis in the ITU is frequently preceded by the development of multiple organ failure as a result of uncontrolled inflammation. Treatment with omega-3 (fish oil) has been demonstrated to attenuate the effects of uncontrolled inflammation and may be clinically beneficial in reducing morbidity from organ dysfunction. Method: A randomised control trial investigating the effects of parenteral omega-3 (OmegavenTM), given early in the course of sepsis, was carried out in a single institution. Consecutive patients diagnosed with sepsis were entered into the study. Patients were randomised to receive either parenteral fish oil and standard medical care or standard medical care only. The primary outcome measure was a reduction in organ dysfunction using the SOFA score as a surrogate marker. The secondary outcome measures were mortality, length of stay, mean C-reactive protein (CRP), days free of organ dysfunction/failure and fatty acid (FA) analysis. Results: Sixty patients were included in the study. The baseline demographics were matched for the two cohorts. Patients treated with parenteral fish oil were associated with a significant reduction in new organ dysfunction (delta-SOFA 2.2±2.2 vs. 1.0±1.5, p=0.005 and maximum-SOFA 10.1±4.2 vs. 8.1±3.2, p=0.041) and mean CRP (186.7±78 vs. 141.5±62.6, p=0.019). There was no significant reduction in the length of ITU and total hospital stay between cohorts. Patients treated with fish oil in the strata of less severe sepsis had a significant reduction in mortality (p=0.042). Conclusion: The treatment of critically ill septic patients with parenteral fish oil is safe. N-3 FAs are rapidly taken up by circulating white cells. It is associated with a significant reduction in organ dysfunction and CRP. It may be associated with a reduction in mortality in patients with less severe sepsis. A multi-centre trial is justified as a result of this trial. 2015-06-02T11:01:48Z 'Schismatical People': Conflict between Clergy and Laity in Warwickshire, 1660-1720 http://hdl.handle.net/2381/32335 Title: 'Schismatical People': Conflict between Clergy and Laity in Warwickshire, 1660-1720 Authors: Harris, Maureen Elizabeth Abstract: The clergy were the focus of early modern parish life, yet their often troubled relationships with parishioners have received little attention from social historians. This thesis offers new evidence by examining the Warwickshire clergy, in the turbulent years between 1660 and the repeal of the 'Occasional Conformity' and 'Schism' acts, as both victims and perpetrators in clerical/lay conflicts. Using the ecclesiastical records of Worcester and Lichfield/Coventry, the two dioceses covering Warwickshire, this study has found clerical authority weakened through contempt, and disadvantaged by the Anglican Church's continued use of medieval methods of ecclesiastical discipline and funding. It has also discovered a strong laity using both legal and subversive tactics to express frustration with the clergy and influence clerical behaviour, by negotiating an acceptable Anglican orthodoxy or by opposing the minister to force his resignation, suspension or deprivation. Mapping of tithe and non-tithe clerical/lay incidents shows that conflict was more frequent in south-west Warwickshire, particularly in the Hundred of Barlichway, than in the north and east of the county. Strong gentry control decreased the likelihood of clerical/lay disputes while the proximity of grammar schools increased them, and the presence of dissenters in conflicted parishes was of major significance. Catholics in particular, but also Quakers and Presbyterians, participated in disputes. Conversely dissenters were few in parishes without recorded conflict. Warwickshire disputes were more prevalent than in the often dispersed settlements of York diocese, and violent hostility towards Warwickshire clergy and their families was greater in 1690 to 1720 than in 1660 to 1689. This study of clergy-centred conflict finds rare examples of harmony in a society of institutionalized informing and malicious intent, and sees frequent clerical/lay antagonism as part of a continuous narrative of religious 'schism' from before the civil wars, through the seventeenth century to the present day. 2015-06-02T10:55:10Z Late cretaceous foraminifera from the Kurdistan region, NE Iraq: palaeontological, biostratigraphical and palaeoenvironmental significance http://hdl.handle.net/2381/32334 Title: Late cretaceous foraminifera from the Kurdistan region, NE Iraq: palaeontological, biostratigraphical and palaeoenvironmental significance Authors: Noori, Rawand Bakir Abstract: The early Turonian-early Maastrichtian planktonic and benthonic foraminiferal faunas of the Kurdistan region, NE Iraq are evaluated. Some 93 planktonic foraminifera (24 species of the family Heterohelicidae are described in detail) from the Kometan and Shiranish formations, and 115 benthonic foraminifera from the Shiranish Formation are identified and illustrated. The fauna reveals new and important data bearing on the palaeontological, biostratigraphical and palaeoenvironmental significance of the Late Cretaceous successions in the Kurdistan region, NE Iraq. Based on the planktonic foraminiferal assemblages, nine biozones and two subzones spanning the early Turonian to late early Maastrichtian were identified. Sequential changes in planktonic foraminiferal assemblages map discrete intervals within the Kometan and Shiranish formations that suggest dominantly warm, nutrient-poor marine surface and near-surface conditions during the mid-Turonian to late Coniacian, latest Santonian, and late Campanian, and cooler more nutrient-rich surface and near-surface waters in the early Turonian, early to late Santonian, early Campanian and early Maastrichtian. Species of the benthonic foraminiferal genus Bolivinoides provide a refined biostratigraphic biozonation for the late Campanian to early Maastrichtian Shiranish Formation in the Kurdistan region, NE Iraq. Three biozones and two subzones are identified for the first time in Iraq: the Bolivinoides decoratus biozone (late Campanian) subdivided into a lower B. decoratus subzone and an upper B. laevigatus subzone; the B. miliaris biozone (earliest Maastrichtian); and the B. draco biozone (late early Maastrichtian). Combined, the Bolivinoides and planktonic foraminiferal biostratigraphy enables the informal recognition of lower and upper intervals within both the Globotruncana aegyptiaca and Gansserina gansseri planktonic foraminifer biozones that may be important for a more refined inter-regional correlation in the Middle East and North Africa. The new Bolivinoides biozonation precisely locates the Campanian-Maastrichtian boundary in NE Iraq. The benthonic foraminiferal assemblages are interpreted as representing outer shelf to middle slope environments, between ca 200 m to at least 600 m water depth, with maximum water depths in the late Campanian, followed by shallowing into the early Maastrichtian. The most likely control mechanism for the shallowing of sea level is the beginning of southern Neo-Tethys Ocean closure at this time. 2015-06-02T10:46:19Z Wavelet theory and its applications in economics and finance http://hdl.handle.net/2381/32315 Title: Wavelet theory and its applications in economics and finance Authors: Lai, Wenlong Abstract: Wavelets orthogonally decompose data into different frequency components, and the temporal and frequency information of the data could be studied simultaneously. This analysis belongs within local nature analysis. Wavelets are therefore useful for managing time-varying characteristics found in most real-world time series and are an ideal tool for studying non-stationary or transient time series while avoiding the assumption of stationarity. Given the promising properties of wavelets, this thesis thoroughly discusses wavelet theory and adds three new applications of wavelets in economic and financial fields, providing new insights into three interesting phenomena. The second chapter introduces wavelet theory in detail and presents a thorough survey of the economic and financial applications of wavelets. In the third chapter, wavelets are applied in time series to extract business cycles or trend. They are useful for capturing the changing volatility of business cycles. The extracted business cycles and trend are linearly independent. We provide detailed comparisons with four alternative filters, including two of each detrending filters and bandpass filters. The result shows that wavelets are a good alternative filter for extracting business cycles or trend based on multiresolution wavelet analysis. The fourth chapter distinguishes contagion and interdependence. To achieve this purpose, we define contagion as a significant increase in short-run market commovement after a shock to one market. Following the application of wavelets to 27 global representative markets' daily stock-return data series from 1996.1 to 1997.12, a multivariate GARCH model and a Granger-causality methodology are used on the results of wavelets to generate short-run pair-wise contemporaneous correlations and lead-lag relationships, respectively, both of which are involved in short-run relationships. The empirical evidence reveals no significant increase in interdependence during the financial crisis; contagion is just an illusion of interdependence. In addition, the evidence explains the phenomenon in which major negative events in global markets began to occur one month after the outbreak of the crisis. The view that contagion is regional is not supported. The fifth chapter studies how macroeconomic news announcements affect the U.S. stock market and how market participants' responses to announcements vary over the business cycle. The arrival of scheduled macroeconomic announcements in the U.S. stock market leads to a two-stage adjustment process for prices and trading transactions. In a short first stage, the release of a news announcement induces a sharp and nearly instantaneous price change along with a rise in trading transactions. In a prolonged second stage, it causes significant and persistent increases in price volatility and trading transactions within about an hour. After allowing for different stages of the business cycle, we demonstrate that the release of a news announcement induces larger immediate price changes per interval in the expansion period, but more immediate price changes per interval in the contraction period, from the old equilibrium to the approximate new equilibrium. It costs smaller subsequent adjustments of stock prices along with a lower number of trading transactions across a shorter time in the contraction period, when the information contained in the news announcement is incorporated fully in stock prices. We use a static analysis to investigate the immediate effects of news announcements, as measured by the surprise in the news, on prices, and adopt a wavelet analysis to examine their eventual effects on prices. The evidence shows that only 6 out of 17 announcements have a significant immediate impact, but all announcements have an eventual impact over different time periods. The combination of the results of both analyses gives us the time-profile of each news announcement's impact on stock prices, and shows that the impact is significant within about an hour, but is exhausted after a day. 2015-05-29T08:47:07Z Profiling of bacterial communities in chronic obstructive pulmonary disease http://hdl.handle.net/2381/32292 Title: Profiling of bacterial communities in chronic obstructive pulmonary disease Authors: Haldar, Kairabi Sadhu Abstract: Introduction: It is hypothesized that bacteria are important in the pathogenesis of COPD and exacerbations. Most bacteriological research in COPD has utilised culture based methods. Novel molecular approaches enable detailed evaluation of the airway microbiome that may better inform the role of bacteria in COPD. This project aimed to characterise the microbial community in COPD at stable state and during acute exacerbations through assessment of serial sputa at stable (S), exacerbation (E), follow up (F) and recovery (R) visits. Methods: Sputum from 145 clinical trial COPD patients was collected at multiple stable visits and at each exacerbation (E, F and R visit) over 12 months. Real-time quantitative PCR (qPCR) was performed on sputum DNA using universal 16S gene primers and specific gene targets to quantify total bacterial load and the specific pathogens H. influenzae, S. pneumoniae, M. catarrhalis and S. aureus. In a subgroup of 30 exacerbating patients, 454 high-throughput pyrosequencing of 16S rDNA amplicons was performed at each of the 4 visits. Results: There was no significant difference in total bacterial load or any specific pathogen between longitudinal stable and exacerbation samples. 454 pyrosequencing identified Proteobacteria and Firmicutes to be the dominant groups contributing >80% of the sequence reads at phylum level. Haemophilus, Moraxella and Streptococcus were the dominant groups at genus level. No significant within-subject change in the microbial community was observed across visits. Cluster analysis, based on the ratio of Proteobacteria to Firmicutes (P:F) characterised three subgroups. The high P:F subgroup was characterised by a significant increase in P:F from S to E visits, associated with raised blood CRP and sputum IL-1β levels, suggesting a role for bacteria in exacerbation pathogenesis for this subgroup. Conclusions: Molecular profiling identifies heterogeneity in the airway microbiome of COPD patients, with a role for bacteria suggested in a subgroup. 2015-05-21T08:18:32Z The structure of aqueous solutions http://hdl.handle.net/2381/32283 Title: The structure of aqueous solutions Authors: Soper, Alan K. Soper 2015-05-18T14:49:10Z The structure and interactions of pneumolysin http://hdl.handle.net/2381/32282 Title: The structure and interactions of pneumolysin Authors: Marshall, Jamie Elton Abstract: Pneumolysin is a major virulence factor of Streptococcus pneumoniae. It is a 53-kDa protein with four domains which form pores in host cells and depletes serum-complement resulting in a diminished host immune response. Despite its importance, the high-resolution structure of pneumolysin is yet to be solved. This thesis seeks to address the lack of high-resolution data, enabling the identification of residues important for pore formation and binding to its cellular target ligand, cholesterol. The interactions between complement and pneumolysin were investigated, to further understand the role of pneumolysin in serum complement depletion. The structure of pneumolysin was solved using X-ray crystallography at 2Å resolution. The crystal packing mimics the pre-pore arrangement of pneumolysin, enabling the identification of intermolecular interactions that stabilise the pre-pore. Mutation experiments revealed interacting residues were not structurally important but resulted in a substantial reduction in the pore forming capability of pneumolysin, showing that they are functionally important and most likely inhibit pre-pore oligomerisation. Residues involved in the interactions are 69% conserved across five proteins of the same family implying a common mechanism. The crystal structure revealed other residues that may be functionally important with respect to domain orientation and cholesterol binding in the pre-pore, and these could be investigated in the future. Complement assays showed that pneumolysin diminished complement in the fluidphase and when immobilized on a surface. However pneumolysin did not interact with IgG and a mutation previously identified as being important (D385N) had no effect on the activity observed. Activation occurred via the alternative pathway, with contributions from the classical and/or the lectin pathway. 2015-05-15T13:24:09Z Heavy metal opacity and line blanketing in hot DA white dwarf stars http://hdl.handle.net/2381/32281 Title: Heavy metal opacity and line blanketing in hot DA white dwarf stars Authors: Preval, Simon Paul Abstract: This thesis concerns atomic data, and it's impact upon white dwarf model atmosphere calculations, and consequentially, the measurements made using such models. The thesis begins with a brief introduction to the history and properties of white dwarfs, the theory of radiative transfer, and the uses of white dwarfs in astronomy. A detailed spectroscopic survey of WD0501+524 (G191-B2B) is presented. 976 absorption features were detected, 947 of which have been successfully identified. ∼ 60% of the identified features were found to pertain to Fe and Ni iv-vi transitions. The potential consequences of using a limited atomic data set in model atmospheres are discussed, and other possible identifications to the unknown absorption features are queried. The Kurucz (1992) (Ku92) atomic database (containing ∼ 9, 000, 000 transitions) is supplemented by photoionisation (PI) cross section data from the Opacity Project for use in stellar atmosphere calculations. The more recent Kurucz (2011) (Ku11) database (containing ∼ 160, 000, 000 transitions) is not accompanied by PI cross section data. Calculations performed to create this data are described, and their effects on model atmosphere calculations are discussed. The Lyman/Balmer line problem, a discrepancy between the measured effective temperatures (Teff) from the Lyman/Balmer line series is considered. Teff and surface gravity (log g) measurements are made of 24 DA white dwarfs using model atmosphere grids utilising two atmospheric compositions, two Stark broadening tables, and the Ku92 and Ku11 atomic data sets. It is shown that the average opacity contributed by all metal species in the atmosphere drives the discrepancy between the measured Lyman/Balmer Teff. Analysis of Extreme Ultraviolet Explorer (EUVE) data for seven metal rich white dwarf stars is presented. Four model atmosphere grids were calculated using two atmospheric compositions (Preval et al. 2013; Barstow et al. 2003) and the Ku92 and Ku11 atomic datasets. Improved fits for wavelengths shortward of 230°A are obtained for all stars except WD0501+524, where significant discrepancies remain. 2015-05-15T13:16:55Z Predisposition to hearing loss in different strains of mouse http://hdl.handle.net/2381/32280 Title: Predisposition to hearing loss in different strains of mouse Authors: Sinclair, James Langley Abstract: This investigation explores the basis of the susceptibility to hearing loss from a neurobiological stand point, in different genetically modified and inbred strains of mice: CBA/Ca (CBA), C57BL/6J (C57), Kv2.2 knock-out (Kv2.2 KO) and USP42 KO. Kv2.2, a delayed rectifier potassium channel, is expressed in the ventral nucleus of the trapezoid body (VNTB) in the auditory brainstem, in which originates the medial olivocochlear system (MOC), an efferent system which protects and regulates the cochlea. Preventing expression of Kv2.2 predisposes mice to noise induced hearing loss. Labelling experiments presented here show Kv2.2 expressing neurons in the VNTB contribute to the population of MOC neurons, implicating regulation of excitability of MOC neurons in protection from hearing loss. The MOC system of the C57 is ineffective, thought to lend this strain predisposition to noise-induced and age-related hearing loss. Whole cell patch clamp was used to compare VNTB neurons of the C57 with those of the CBA, a different inbred strain with an effective MOC, in order to determine if differences in excitability exist between strains that may explain the differing strength of their respective MOC systems. Pre-hearing onset, the neurons of the VNTB were identical. Post hearing onset, electrophysiological characteristics diverged: the VNTB neurons of the CBA were able to support higher firing rates due to slower inactivation of its voltage-gated potassium currents. The role of inflammation in hair cell loss in the C57 was probed by knocking out USP42, a gene involved in cell-cycle arrest in response to metabolic damage, highlighting changes in the cochlear nuclei following peripheral loss of sensitivity. The changes observed in the VNTB and cochlear nuclei highlight the importance of activity dependent changes and homeostatic regulation of excitability in the central auditory system. 2015-05-15T12:59:51Z Past conceptions of environmental rights : tensions and solutions http://hdl.handle.net/2381/32258 Title: Past conceptions of environmental rights : tensions and solutions Authors: Dodsworth, Ashley Harriman Abstract: This thesis will argue that environmental rights are not new, that they are not the response of the modern world to unique contemporary problems. Contributing to two areas of scholarship within environmental political theory, that of re-examining the political canon and developing the concept of environmental rights, it will show that there is a tradition of engagement with the concept of rights to natural resources within past political theory. This argument will be proved through an examination of past political texts, drawn from thinkers as varied as the republican theorists Niccolò Machiavelli and James Harrington, the natural rights thinkers Hugo Grotius and John Locke, the eighteenth-century radicals and the leading theorists of the nineteenth century, Karl Marx and John Stuart Mill. As a result of this analysis, it will be clear that previous political thinkers were aware of the problems inherent in securing the rights of all to finite resources. Through their work on rights, and specifically environmental rights, labour and property, they engaged with the contradictions at the heart of this concept. Yet the value of the previous work on environmental rights does not rest only on their awareness of these tensions but in their responses. These thinkers reimagined and reconceptualised environmental rights as limits to property; as justification for reclaiming and redistributing resources; as entitlements to 'as good' equivalents and as necessitating the exclusion of some from natural resources. This examination of awareness of these inherent tensions and the creative solutions offered in response shows the depth and variety of the past conceptions of environmental rights. The historically informed understanding of environmental rights that results is one which endeavours to balance the claims, equality and freedom of all in the face of finite resources, offering both a source of inspiration and variety of options for contemporary environmentalists. 2015-05-12T09:19:54Z Relationships between nuclear lamins and telomere biology in progeroid laminopathies and cancer http://hdl.handle.net/2381/32257 Title: Relationships between nuclear lamins and telomere biology in progeroid laminopathies and cancer Authors: Turner, Rachel Abstract: Telomeres are essential for maintaining the integrity of the genome. Shortening and dysfunction of telomeres initiates cellular senescence, halting further cell division, and instigating alterations in biological processes which contribute to ageing. Progeroid syndromes are disorders of ageing. Patients exhibit not only an early external appearance of old age, but several age-related diseases including osteoporosis, muscle wasting and cancer. Laminopathies are diseases caused by mutations in LMNA, the gene encoding the key nuclear matrix component lamin A. Some mutations result in progeroid phenotypes that are associated with elevated levels of senescent cells. The rate of telomere shortening in progeria cells was found to be accelerated relative to healthy controls, confirming a role for lamin A function in telomere biology. In order for a cell to bypass the protective mechanism of senescence, it must initiate a telomere maintenance mechanism (TMM), resulting in cancer. Several biological changes accompanying the alternative lengthening of telomeres (ALT) TMM overlap with mechanisms affected by changes in lamin biology. As such, lamins and related nuclear proteins were investigated in ALT cells and found to differ from tumour-derived cells which activate the telomerase-based TMM. It was found that although nuclear levels of lamins differed between cells of the two TMMs, the interaction of lamin A with chromatin was not altered. Localisation studies of lamin A revealed different distribution of lamins in the nucleus. An excess of intranuclear lamin observed in ALT cells is proposed to be permissive for recombination-based processes required for telomere elongation through ALT, whereas laminopathy lines exhibit a reduced intranuclear lamin, and an accompanying DNA damage repair deficiency. These findings reinforce the importance of lamin organisation and intranuclear network stability in chromatin maintenance, and highlight a new role for lamins in ALT cancers. 2015-05-12T09:11:42Z Analysis of the fitness cost of integrons in clinical isolates of acinetobacter baumannii http://hdl.handle.net/2381/32256 Title: Analysis of the fitness cost of integrons in clinical isolates of acinetobacter baumannii Authors: Horvath-Papp, Eva Abstract: Antibiotic resistance determinants carried on mobile genetic elements such as integrons are widespread in Acinetobacter baumannii. A total of 76 clinical isolates of A. baumannii were screened for class 1, 2 and 3 integron structures using PCR-based assays. Further chromosome walking and Southern blot-based analyses revealed a significant proportion of incomplete integrons, primarily due to IS element-mediated deletions or truncations at the 5' end of these integrons. Based on these multiple detection methods, a total of 72 integron structures distributed among 58 isolates were identified. Remarkably, 29 (40.3 %) were either incomplete, or had a truncated integrase gene. These data also revealed that using established PCR-based detection methods alone would yield high rates of false-negative and –positive results. The high frequencies of intI1 and/or 5' end integron truncations suggest that IntI1 amelioration confers a significant selective advantage. This hypothesis was investigated in E. coli and A. baumannii backgrounds using an IPTG-inducible IntI1-expressing plasmid. Significant fitness costs were observed through growth curve analysis when IntI1 was overexpressed in recA-deficient E. coli lab strains, and also in an A. baumannii strain. The latter was predicted to have a ~1.5-fold higher number of non-canonical IntI1 recombination sites in a typical E. coli strain. The archetypal intI1 repressor, LexA, is not present in the A. baumannii genome, so the role of the closest homologue, ∆UmuDAb, was investigated through knockout studies. ΔumuDAb mutants were created through allelic exchange, and although the mutants showed a significant upregulation of intI1 expression, when the mutants were complemented with a umuDAb-overexpressing plasmid, intI1 expression was also increased, albeit to a lesser extent. This study demonstrates a complex DNA-damage response in A. baumannii, and will aid further investigation for a full understanding of the development and maintenance of antibiotic resistance in this important nosocomial pathogen. 2015-05-12T08:54:43Z The serine/threonine protein kinases of Burkholderia pseudomallei http://hdl.handle.net/2381/32255 Title: The serine/threonine protein kinases of Burkholderia pseudomallei Authors: Pankhania, Depesh Abstract: Burkholderia pseudomallei is a Gram-negative bacterium that is endemic in tropical and sub-tropical regions. B. pseudomallei is an opportunistic pathogen and is the causative agent of the human disease, melioidosis, which accounts for 20% of all septicaemic deaths in Thailand. The phosphorylation via serine/threonine protein kinases (STKs) coordinates a vast array of signal pathways in both eukaryotic and prokaryotic organisms. In bacteria these pathways include: biofilm formation, cell wall biosynthesis, metabolism, sporulation, stress response and virulence. In this study, I identified six genes in the B. pseudomallei K96243 genome, bpsl0220, bpsl0571, bpsl0597, bpsl1828, bpss1584 and bpss2102 encoding putative STKs. The importance of these enzymes in B. pseudomallei was not determined to date, and thus the aim of this study is to Understand the roles of these proteins in B. pseudomallei virulence and regulations of Cellular processes. Four of the genes, bpsl0220, bpsl0597, bpsl1828, and, bpss2102, were successfully cloned and over-expressed the putative STKs in Escherichia coli and the recombinant proteins were purified. Each of the recombinant proteins exhibited autophosphorylation as well as phosphorylation of a general kinase substrate in vitro, thus demonstrating that each of the four proteins has protein kinase activity. Furthermore, I constructed specific mutants in each of the four STK-encoding genes in B. pseudomallei. These mutants were assessed in a variety of in vivo and in vitro, assays. The inactivation of the genes in B. pseudomallei, identified a switch in colony morphotype may be associated with a change in lipopolysaccharide structure and the motility of the bacteria, which warrants further study. One of the mutants, Δbpsl1828 displayed a conditional temperature sensitivity in distilled water, and thus the protein encoded by this gene could potentially contribute to the ability of B. pseudomallei to persist in the tropical and sub-tropical environments. However, future work is required to confirm a role of BPSL1828 in the regulation of environmental stress. A second mutant, Δbpsl0220, was avirulent in the Galleria mellonella model of disease, and introducing the full-length gene into the mutant complemented the phenotype. This result suggests that BPSL0220 may play a role in virulence. However, future work should assess the Δbpsl0220 deletion mutant in the mouse model of melioidosis. If these results confirm the role of BPSL0220 in pathogenicity, subsequent work could investigate if BPSL0220 maybe used as a target for therapeutic treatment of B. pseudomallei. 2015-05-12T08:45:49Z Assessment of lung alveolar development in childhood and adolescence using 3-helium magnetic resonance http://hdl.handle.net/2381/32245 Title: Assessment of lung alveolar development in childhood and adolescence using 3-helium magnetic resonance Authors: Narayanan, Manjith Abstract: The major functional units of the lung called alveoli, are located in the periphery of the lung. Despite their functional importance, it has been difficult to evaluate their structure and development. Until the advent of 3-Helium magnetic resonance (3HeMR), it was not possible to directly assess peripheral lung structure in a living individual. When this study commenced, the prevailing hypothesis was that human alveolarization was complete by 3 years. It was believed that preterm birth would lead to persisting alveolar damage. The role of other factors affecting human lung development were not clearly understood. In this work, I describe the use of 3HeMR to : 1. Examine the current hypothesis regarding normal alveolar development, 2. Determine whether birth at very preterm gestation leads to long-term alveolar damage and 3. Evaluate factors affecting human alveolar development. First, we determined alveolar size using 3HeMR in healthy subjects aged 7 to 21 years. Alveolar dimensions did not increase by the expected rate over this age range, despite lung capacity increasing nearly fourfold. The only plausible explanation is new alveoli forming throughout the period of lung growth. Then, we compared alveolar size between children born very prematurely (<32 weeks gestation), including survivors of neonatal chronic lung disease (CLD) with term born children and children born mildly preterm (33-36 weeks gestation). Alveolar dimensions were nearly identical suggesting alveolar catch up growth in the very preterm groups. In the third part of the study, we investigated the relationship between various risk factors and alveolar dimensions. Exposure to environmental tobacco smoke (ETS) was found to be consistently associated with larger alveoli, suggesting its detrimental effect on alveolar development. Our results imply that developing lungs have the potential to recover from early life insults. Conversely, the window for adverse environmental exposures to affect alveolar development may be wider than previously believed. 2015-05-08T11:29:19Z Climate and variability of water vapour in the troposphere http://hdl.handle.net/2381/32243 Title: Climate and variability of water vapour in the troposphere Authors: Trent, Timothy James Abstract: Atmospheric water vapour is an important (natural) greenhouse gas, infuencing both directly and indirectly the global radiative balance of the Earth as well as heat and moisture fluxes at the surface. Since water vapour concentrations may change as a result of surface warming and other environmental/meteorological factors, there is a need to understand the long-term behaviour. Changes are small, so it is critical to use high quality data with well-defined uncertainties and biases, particularly for climate research. Hyper-spectral infrared (IR) sounders such as the Infrared Atmospheric Sounding Interferometer (IASI) and the Atmospheric Infrared Sounder (AIRS) allow for higher vertical resolution profile measurements of water vapour to be obtained compared to their predecessors. First results of global comparisons of AIRS profiles show that for tropospheric layers between 925-374 hPa biases are within +-10% and a significant dry bias of 20% in regions of the upper troposphere, consistent with recent comparisons to reanalysis. A consistent approach to the retrieval of temperature and water vapour profiles from all hyper-spectral IR sounders is outlined and an initial set of retrievals from IASI at global climate sites is performed. Results from the University of Leicester Water Vapour Processor (UoL-WVP) show errors of ≈1 K and Atmospheric water vapour is an important (natural) greenhouse gas, infuencing both directly and indirectly the global radiative balance of the Earth as well as heat and moisture fluxes at the surface. Since water vapour concentrations may change as a result of surface warming and other environmental/meteorological factors, there is a need to understand the long-term behaviour. Changes are small, so it is critical to use high quality data with well-defined uncertainties and biases, particularly for climate research. Hyper-spectral infrared (IR) sounders such as the Infrared Atmospheric Sounding Interferometer (IASI) and the Atmospheric Infrared Sounder (AIRS) allow for higher vertical resolution profile measurements of water vapour to be obtained compared to their predecessors. First results of global comparisons of AIRS profiles show that for tropospheric layers between 925-374 hPa biases are within +-10% and a significant dry bias of 20% in regions of the upper troposphere, consistent with recent comparisons to reanalysis. A consistent approach to the retrieval of temperature and water vapour profiles from all hyper-spectral IR sounders is outlined and an initial set of retrievals from IASI at global climate sites is performed. Results from the University of Leicester Water Vapour Processor (UoL-WVP) show errors of ≈1 K and ≤20% within the troposphere for temperature and humidity respectfully. The significance of surface characterisation at a sub-pixel level is also demonstrated. Retrievals from IASI at selected climate sites for 2012 are inter-compared in a three-way analysis with high resolution radiosonde profiles and AIRS data. Results show that the mean standard deviation of observational error for IASI is 2.2% while AIRS is 3.6%. This thesis work represents a step forward in the use of AIRS and IASI data for climate research. However, proven long-term stability is needed for the water vapour data question to be answered. and humidity respectfully. The significance of surface characterisation at a sub-pixel level is also demonstrated. Retrievals from IASI at selected climate sites for 2012 are inter-compared in a three-way analysis with high resolution radiosonde profiles and AIRS data. Results show that the mean standard deviation of observational error for IASI is 2.2% while AIRS is 3.6%. This thesis work represents a step forward in the use of AIRS and IASI data for climate research. However, proven long-term stability is needed for the water vapour data question to be answered. 2015-05-08T11:16:13Z