5357 research outputs found
Sort by
Evaluation of salivary sirtuin 2 as a novel biomarker for periodontitis
Get PDFPhD ThesisSIRT2 is an NAD-dependent histone deacetylase (HDAC) that is involved in the regulation of
gene expression and protein function. This study aimed to evaluate SIRT2 as a salivary
biomarker for periodontitis and investigate any association between SIRT2 and the
inflammatory processes relevant to periodontitis.
Immune responses were investigated in vitro using THP1 monocytes differentiated into
macrophages using phorbol 12-myristate 13-acetate (PMA) and stimulated with TLR2 or TLR4
agonists.
Analysis using qPCR and western blotting showed there were no significant changes to SIRT2
mRNA or intracellular protein expression respectively after stimulation with TLR agonists.
Secreted SIRT2 levels measured by ELISA were significantly elevated after stimulation with
TLR2 agonists but not after stimulation with TLR4 agonists. TLR agonists had no effect on SIRT2
deacetylation activity in macrophages. Inhibition experiments in macrophages showed that
SIRT2 regulates secretion of TNFα, IL-6, IL-8, and IL-1β as measured by ELISA. Multiple
regression analysis (ANCOVA) showed that SIRT2 was significantly elevated in periodontitis
when accounting for the influence of age but SIRT2 levels did not correlate with clinical
measurements of periodontitis such as bleeding on probing and pocket depth. Receiver
operating characteristic (ROC) curve analysis showed that salivary SIRT2 could detect
periodontitis with a high degree of sensitivity and specificity (AUC 89%).
In summary, SIRT2 levels accurately represent the presence of periodontitis, but do not
correlate with clinical measures of periodontitis, which may limit its utility as a diagnostic
biomarker. We have demonstrated a novel TLR2-mediated pathway of SIRT2 secretion from
THP1-derived macrophages which may explain the elevated levels of SIRT2 present in the
saliva of patients with periodontitis but will require further investigation. We have also shown
that SIRT2 mediates the secretion of pro-inflammatory cytokines after stimulation with TLR
agonists which may be of relevance to the pathogenesis of periodontitis
Optimization of System Identification for Multi-Rail DC-DC Power Converters
Get PDFPh. D. Thesis.There have been many recursive algorithms investigated and introduced in real time
parameter estimation of Switch Mode Power Converters (SMPCs) to improve estimation
performance in terms of faster convergence speed, lower computational cost and higher
estimation accuracy. These algorithms, including Dichotomous Coordinate Descent (DCD) -
Recursive Least Square (RLS), Kalman Filter (KF) and Fast Affine Projection (FAP), etc., are
commonly applied for performance comparison of system identification of single-rail power
converters. When they need to be used in multi-rail architectures with a single centralized
controller, the computational burden on the processor becomes significant. Typically, the
computational effort is directly proportional to the number of converters/rails. This thesis
presents an iterative decimation approach to significantly alleviate the computational burden of
centralized controllers applying real-time recursive system identification algorithms in multirail power converters. The proposed approach uses a flexible and adjustable update rate rather
than a fixed rate, as opposed to conventional adaptive filters. In addition, the step size/forgetting
factors are varied, as well, corresponding to different iteration stages. As a result, reduced
computational burden and faster model update can be achieved. Recursive algorithms, such as
Recursive Least Square (RLS), Affine Projection (AP) and Kalman Filter (KF), contain two
important updates per iteration cycle. Covariance Matrix Approximation (CMA) update and
the Gradient Vector (GV) update. Usually, the computational effort of updating Covariance
Matrix Approximation (CMA) requires greater computational effort than that of updating
Gradient Vector (GV). Therefore, in circumstances where the sampled data in the regressor
does not experience significant fluctuations, re-using the Covariance Matrix Approximation
(CMA), calculated from the last iteration cycle for the current update can result in
computational cost savings for real- time system identification. In this thesis, both iteration rate
adjustment and Covariance Matrix Approximation (CMA) re-cycling are combined and applied
to simultaneously identify the power converter model in a three-rail power conversion
architecture.
Besides, in multi-rail architectures, due to the high likelihood of the at-the-same-time need
for real time system identification of more than one rail, it is necessary to prioritize each rail to
guarantee rails with higher priority being identified first and avoid jam. In the thesis, a workflow,
which comprises sequencing rails and allocating system identification task into selected rails,
was proposed. The multi-respect workflow, featured of being dynamic, selectively pre-emptive,
cost saving, is able to flexibly change ranks of each rail based on the application importance of
rails and the severity of abrupt changes that rails are suffering to optimize waiting time and
make-span of rails with higher priorities
Rights to dducation and employment for persons with disabilities in Nigeria : towards a human rights model of disability
Get PDFPhD ThesisNigeria is a party to several international and regional instruments including the Convention on
the Rights of Persons with Disabilities, and more recently the 2030 Agenda on Sustainable
Development which guarantees explicitly the education and employment rights of persons with
disabilities. These international instruments impose obligations on states including Nigeria in the
implementation of education and employment for persons with disabilities. Therefore, this thesis
evaluates Nigeria’s progress in achieving the (Sustainable Development Goals) SDGs by
considering whether Nigeria is meeting its international obligations for persons with disabilities in
education and employment.
Applying the 4As (Adaptability, Acceptability, Availability, and Accessibility) and disability
human rights frameworks, this thesis contends that although Nigeria has made some progress
towards achieving the SDG goals 4 and 8, and has adopted some measures to protect and promote
the education and employment rights of persons with disabilities, yet the country is still failing to
meet its obligations to make education and employment acceptable, adaptable, available, and
accessible to persons with disabilities. Moreover, Nigeria continues to promote the moral/medical
approaches to disability rather than the human rights model of disability in its domestic framework
and practices relevant to persons with disabilities in education and employment.
For Nigeria to comply with its international obligations, it needs not only to move towards a human
rights model of disability in its domestic laws, policies, and practices relevant to persons with
disabilities in education and employment but also, shift towards protecting and promoting the
rights of people with disabilities in these areas, by providing more financial resources and making
procedural, institutional, substantive, and cultural changes. A shift towards a human rights model
of disability by Nigeria will significantly improve the situation of persons with disabilities as well
as ensure Nigeria’s progress in achieving inclusive quality education and full productive
employment for persons with disabilities in line with the 2030 Agenda on Sustainable
Development
Re-Designing Planning Policy Processes and Embedding Technology: The Case of Neighbourhood Planning
Get PDFPh. D. ThesisNeighbourhood planning provided citizens with new rights through the Localism Act 2011, empowering them to organise together to produce their own policy which would be adopted by local planning authorities. By December 2020, over 2700 communities had embarked on the neighbourhood planning process with just under 1000 plans adopted. However, challenges remain in the way neighbourhood planning is enacted by citizens with a complex process, uneven geographical take up and a lack of appropriate support for citizens. At a broader level, citizen participation in policymaking processes has shown a contested picture over many decades with calls for more and better participation whilst questions of the level of influence such participation has on decisions have been raised. Furthermore, the configuration of citizen participation has long been questioned, particularly in relation to the methods used to reach out to communities. Alongside this, research regarding digital technology for policymaking and citizen participation has increased but has yet to have an impact in practice.
In this research, I explore how digital and non-digital tools could be designed to better support citizens to shape places through the example of the neighbourhood planning policy process. I engaged with neighbourhood planning groups and planners to learn from their experiences, particularly centring citizens’ needs in considering the need for support in the citizen-led policy tool. Using an action research approach, I used a cycle of action and reflection to inform research design, enabling participants to help direct research through their own experiences. To understand how citizens enact the neighbourhood planning process and explore the use of digital tools, I engaged in an exploratory deployment of a participatory media technology, then moved to deliver interactive workshops to explore the neighbourhood planning process in-depth and co-designed new modes of digital and non-digital engagement.
Through this research, I first demonstrate the complexity of neighbourhood planning, exploring the nuances of the process from a citizens’ perspective and, second, I identify both opportunities and barriers to the use of digital modes of participation. Through identifying the issues within the neighbourhood planning process, I put forward approaches to designing better support mechanisms to enable citizens to shape places, including two key design principles, cross-disciplinary design thinking and inclusive design, which can ensure an inclusive and equitable approach to the design of policy and support tools. I demonstrate how these design principles should manifest within the neighbourhood planning context and provide recommendations for specific policy changes and the development of digital and non-digital support. Ultimately, I argue the need to design and embed digital and non-digital tools and technologies within a re-designed neighbourhood planning process to enable an appropriate, navigable and sustainable citizen-led policy tool where modes of participation can link directly to policy outcomes allowing citizens to shape places
Exploration of sleep as a specific risk factor for poor cardiometabolic and mental health & the comparison of subjective and objective assessments of sleep
Get PDFPh. D. ThesisNumerous studies have attempted to evaluate the impact of sleep on cardiometabolic and mental health, although most of the population-based studies utilised self-reported sleep assessment and health status. Therefore, the main aim of this project is to explore the relationship between accelerometer measured sleep and cardiometabolic and mental health amongst the UK Biobank participants.
The UK Biobank collected extensive information of the general UK population. They have also collected accelerometry data allowing the extraction of sleep duration and quality. Disease status was obtained from their primary care record. Out of the 84,411 participants with available processable accelerometry data, 17.3% slept 8 hours/night. Short sleep duration was significantly associated with the male gender, older age, high body mass index, social deprivation and ethnic minority group (p<0.001). A significant ‘U-shaped’ association was found between sleep duration and metabolic disease status. Both short and long sleep durations were also associated with negative mood and worse cognitive performances including slower reaction time and worse visual memory (p<0.001). These findings showed the importance of sleep in maintaining health. However, sleep misperception was found to be common leading to a discrepancy between subjective and objective measurements of sleep.
A cross-sectional analysis was conducted on 28 human participants (11 controls and 17 patients). Sleep was assessed using a paper sleep diary, wrist-worn tri-axial accelerometer and laboratory-based polysomnography. The level of cortisol, melatonin, mitochondrial DNA damage and gene expression was measured using saliva, urine, skin swab and hair samples, respectively. An overestimation of sleep duration was observed in this study which is consistent with the UK Biobank analysis. Patients were found to have a longer sleep duration, but a lower sleep efficiency. Moreover, patients were found to have a lower level of melatonin and cortisol. A ‘U-shaped’ association was found between sleep duration and mitochondrial DNA damage level. Finally, circadian rhythm and mitochondria-related pathways have been identified in the gene expression analysis. However, these associations were not found to be statistically significant. Therefore, it is proposed that larger sample size should be considered in future studies informed in part by further power calculations based upon the findings presented in the current thesis.BBSRC and Unileve
The molecular basis of telomere-mediated chromosome pairing and genetic exchange during prophase I of meiosis
Get PDFPhDProphase I encapsulates the unique and defining events of meiosis; chromosome pairing, homologous
recombination, synapsis, and subsequent segregation, to produce genetically unique haploid germ cells.
These essential processes depend on a variety of protein complexes including the meiotic telomere
complex (MTC), the synaptonemal complex (SC) and the meiotic recombination machinery. To carry
out homology searches chromosomes must be tethered to the nuclear envelope, this is achieved by
interplay between the MTC proteins (MAJIN, TERB1, and TERB2) and the shelterin complex protein,
TRF1. Once attached, chromosomes undergo rapid prophase movements to find their homologous
partner and begin to synapse. This involves the formation of the universally conserved SC structure
along the lengths of aligned homologues. The SC provides the essential structural framework for HR
and the crossover (CO) pathway. CO formation is dependent on the pro-CO machinery, including the
E3 ligase proteins, HEI10 and RNF212.
The main focus of this thesis is to use biophysical and structural approaches to deepen our understanding
of the roles and mechanisms of the proteins and protein complexes involved in these meiotic processes.
Here, we report the structural basis of the mammalian MTC and provide a mechanistic insight into
chromosome tethering at the inner nuclear membrane (INM) achieved by the MTC. We show that the
MTC recruits telomere-bound TRF1, through the 2:1 TRF1:TERB1 interaction, and undergoes
subsequent structural rearrangement to displace TRF1 allowing the MTC to directly bind telomeric
DNA and subsequently stabilise telomere-INM connectivity. The core architecture of mammalian SC
is provided through the self-assembly of the transverse filament (TF) protein, SYCP1. We provide the
first structural analysis of the D. melanogaster SC, specifically the TF protein, C(3)G. Biophysical
analysis reveals that the central α-helical domain of C(3)G form dimers in a side-by-side parallel
arrangement, but has some propensity to tetramerise, which could serve as building blocks for the
recruitment and assembly of the complete SC. We show that HEI10 forms an obligate tetrameric
structure and RNF212:RNF212b for a highly stable 2:2 complex and propose a structural model for the
human E3 ligase proteins based upon solution scattering studies. Together, these findings provide a
solid foundation for elucidating the mechanisms of mammalian meiosis
Essays on agricultural commodity prices
No full textPh. D. Thesis.Interests in commodity price dynamics are not new phenomena. Booms and slumps in recent
decades have renewed the interest in understanding the factors behind agricultural commodity
price movements. This thesis includes a collection of empirical chapters concentrate on critical
aspects concerning the movement behaviours of selected grains prices in the United States. In
particular, this thesis contributes to studies in applied commodity price analysis.
The agricultural commodity price is characterised as being highly volatile and the factors lying
behind these fluctuations are characterised by a significant complexity. Chapter 2 discusses the
agricultural commodity price developments and main factors associated with agricultural
commodity price dynamics in the United States. This chapter leads the subsequent chapters
with the motivations for the selected factors discussed in this thesis and the technical methods.
Using data on energy markets and agricultural commodity export prices, chapter 3 identifies
the long-term co-movements between diesel prices and corn export prices in the U.S.,
considering diesel powers the U.S. economy in exporting agricultural commodities and
offering long-term productivity gains in the fundamental sectors. The analysis provides
evidence of a positive connection between diesel prices and corn export prices in the long-term.
Besides, by employing the quantile-based analysis, this study also finds the long-run relations
between corn and diesel prices vary over different market conditions. The findings in chapter
3 imply that the response of corn export prices to changes in diesel prices is generally much
steeper when corn export prices at normal levels than in extreme levels.
Considering the threats of climate changes on agricultural commodity production, chapter 4
analyses the effects of extreme climate events on the movements of agricultural commodity
price. Particularly, the chapter explores the extent by which changes in an important climate
phenomenon, El Niño Southern Oscillation (ENSO), have contributed to the dynamics of
grains prices in the United States. Previous works contribute to the belief that the dynamic
relation of ENSO events on grain prices should be nonlinear in nature. To take the climate
volatility information and nonlinear feature into account, this analysis fits an interval-based
threshold model. This chapter finds that the warm condition increases the prices of soybeans
II
and corn, and the cooler condition has an impact on wheat and corn. These results can help
form policies on storage and production decisions.
Chapter 5 provides evidence for the agricultural commodity market efficiency of the United
States on the causal effects of agricultural commodity futures prices on cash prices. Applying
three time-varying methods, with placed on grains markets including wheat, soybean and corn,
chapter 5 finds that the causal effects between futures and cash prices change over time and
depend on agricultural commodity markets. This chapter has proved that the cash and futures
prices linkages behave differently in wheat and soybean, corn markets, implying a time-varying
bidirectional causality in the wheat markets but unidirectional causal effects in the soybean and
corn markets.
The joint theme and main contribution of this thesis lie on providing new evidence in relevant
issues in applied agricultural commodity prices analysis by employing econometric methods
in a novel wa
Professional learning re-constructed through narrative inquiry in the United Arab Emirates
Get PDFPhD ThesisResearch on teacher educators’ professional learning within the United Arab Emirates is an
emerging field. My roles as a senior educational professional have inspired my interest in the
professional learning of teacher educators and specifically in reflecting on my own professional
learning. This study adopts a narrative inquiry approach to my personal and professional learning
in the United Arab Emirates. As a teacher educator, I operate within a complex cultural and
economic environment that is underpinned by Emirati culture, Islamic values and a neo-liberal,
market-based approach to education. As a result, I have worked in various professional roles with
a high degree of uncertainty, and I have navigated unfamiliar professional boundaries to achieve
personal agency. There are three main phases of this study which has taken place over a six year
period; the first phase captures my thinking as an early career teacher, before progressing to a
teacher educator role working across schools, and then working in a senior role, juggling a range
of commercial and educational responsibilities. In order to make empowering decisions about my
professional learning, I have needed to develop a set of researcherly dispositions, which has
emerged from my awareness of the contextual challenges and opportunities within the UAE
education sector. My narrative as a teacher educator is illustrated with cameos of two teacher
educators and a teacher with whom I have worked, each with unique profiles and development
needs that have informed my approach to the design of professional learning opportunities.
Through my work with these educators I explore the conditions that have supported my
professional growth and outline the impact this has had on me. This narrative study, which draws
on European models, namely the Dutch Standards (VELON) and the Flemish Teacher Educator
Development Profile (VELOV) and also Kelchtermans ‘Dynamics of Learning’ model (2018),
demonstrates that I have been required to exhibit certain dispositions that are relevant to the UAE
education context in order to perform in a variety of professional roles. The findings of this study
reveal that I have examined my professional contexts in pursuit of personal agency, and
attempted to capture the nuances of my professional learning, and the professional learning o
The Role of Phosphate Acquisition in Promoting Stress Resistance and Virulence in a Major Human Fungal Pathogen
Get PDFPh. D. Thesis.The ability of pathogenic fungi to obtain essential nutrients from the host is vital for virulence. In Candida albicans, acquisition of the macronutrient phosphate (Pi) is regulated by the Pho4 transcription factor, which is important for both virulence and resistance to diverse and physiologically important stresses. A key aim of this work was to investigate the regulation of Pho4, and the roles of Pho80-Pho85 cyclin dependent kinase (CDK) signalling and inositol polyphosphates were explored. As reported in the model yeast Saccharomyces cerevisiae, the Pho80 cyclin functions as a negative regulator of Pho4 in C. albicans. However, in contrast to S. cerevisiae, the CDK inhibitor Pho81 also negatively regulates C. albicans Pho4; Pho4 accumulates in the nucleus in pho81Δ cells and Pi acquisition strategies are activated under Pi replete conditions. With regard to inositol polyphosphates, in contrast to that reported in S. cerevisiae, IP7 synthesis by the Kcs1 inositol pyrophosphate synthase was found to be largely dispensable for Pi homeostasis with Vip1-derived IP7 synthesis playing a more prominent role in C. albicans.
The synthesis of the Pi storage molecule polyphosphate (polyP) is also regulated by Pho4. Previous work found that mobilization of Pi from polyP is one of the first responses evoked in response to Pi starvation and precedes activation of the Pho4 transcription factor. A further aim of this thesis was to investigate the importance of polyP mobilisation in the pathobiology of C. albicans. It was found that two polyphosphatases, Ppn1 and Ppx1, function redundantly in C. albicans to release Pi from polyP. Strikingly, it was shown that polyP mobilisation plays a role in Pho4 activation and stress resistance in C. albicans. Blocking polyP mobilisation also resulted in significant morphological defects. Consistent with these findings, data is also presented illustrating that polyP mobilisation is important for the virulence of C. albicans.
Given the links between Pi acquisition and virulence, a further aim was to explore whether Pi acquisition could be exploited as a novel antifungal strategy. High-throughput screening of compound libraries revealed potential candidates directly targeting the PHO pathway, which present an exciting avenue for future work.
Taken together, the findings presented in this thesis reveal novel insight into Pi homeostasis mechanisms in C. albicans and the potential of targeting this important virulence trait in the development of future therapeutic strategies
The impact of urban form and shading on microclimate and indoor air temperatures of dwellings: a case study of Erbil, Kurdistan, Iraq
Get PDFPhD ThesisThe history of the Kurdistan region of northern Iraq is complex, however it was established as an
autonomous region (Kurdistan‐Iraq) in 1991, since when it has flourished in stark contrast to the
remainder of Iraq and Syria. The capital of Kurdistan is the historic city of Erbil one of the most ancient
cities in the world (with at least 4000 years of history). In recent times, the city has expanded
dramatically after 2003, in a series of concentric rings around the central ancient Citadel, to
accommodate Kurds from both Kurdistan‐Iraq and the returning diaspora. This rapid urban expansion
has turned its back on the traditional design principles of the ancient Citadel which was designed to
work in harmony with the hot dry climate; organic designs of narrow, winding streets designed around
the needs of the pedestrian. Instead this organic morphology has been replaced by grid‐iron planning,
with street widths designed to accommodate motor vehicles. The alignment of these grid‐iron street
patterns has been driven by geometry rather than referencing urban micro climatic needs.
The main aim of this research is to investigate the impact of urban form and shading on the urban
micro climate and the indoor air temperature of dwellings in the new (post 2003) developments of
Erbil. To achieve these aims two methods were used: The prediction of the urban micro climate used
ENVImet, a numerical climate simulation program. The indoor air temperatures were predicted using
the building energy simulation software IES Virtual Environments (IES‐VE). The climate modelling
compared traditional and grid‐iron morphologies and demonstrated that the traditional morphology
produced lower external air temperatures. For the modern grid‐iron morphologies, higher wind
speeds in the urban canyons were achieved when the prevailing wind from the South West flowed
through a canyon grid aligned North‐South and East‐West. Shading by both trees and wire mesh was
modelled. Both reduce the external mean radiant temperature, but have little impact on the external
air temperature. Moreover, the wire mesh shading did not reduce the urban wind speeds, but the tree
shading did reduce urban wind speeds.
When shading buildings, the reduction in indoor air temperature was small; whilst the shading mesh
reduced solar gain it also reduced night‐time losses to the clear night sky, yielding a small reduction
in indoor air temperature. However, when purposeful night‐time ventilation was modelled, the
reduction in indoor air temperature was significant. By combining building shading (reducing solar
gain) and night time purpose ventilation (increasing nigh‐time cooling) allows greater freedom in
façade design. This permits modern house design to have a similar thermal performance to the
traditional house design. The study has developed a novel method to simulate efficiently wire mesh
shading both for urban micro climates and buildings. It has shown how the modern grid‐iron urban
morphology can be adapted to provide improved micro climates and how individual houses can be
designed to benefit from these changed micro climates. For the future, it is recommended that full
scale testing of whole housing shading be undertaken and how this shading can be adapted to reflect
the local identity of the region