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Ageing, colonic health, obesity and the gut microbiota
Get PDFPh.D. Thesis.Ageing, obesity and history of adenomatous polyps are recognised risk factors for colorectal
cancer (CRC). In recent decades, patterns of colonic microbiota and their major metabolites,
the short chain fatty acids (SCFA), have been proposed as potential additional candidate
biomarker of CRC risk. For example, Fusobacterium nucleatum, which adheres to colonic
enterocytes, stimulates the b-catenin pathway, and reinforces inflammatory responses has
been associated with CRC pathogenesis.
Within the Biomarkers Of Risk of Colorectal Cancer (BORICC)Follow-Up (BFU) and Biomarkers
Of CRC After Bariatric Surgery (BOCABS) Studies, I have investigated relationships between
ageing, colonic health (prior history of adenomatous polyps) and obesity and the gut
microbiota and SCFA. Stool samples from 219 BORICC Study participants, 26 of whom had
paired samples at follow-up (BFU Study), and 30 BOCABS Study participants, including 19
paired pre-and post-bariatric samples, were used. Illumina sequencing of the 16S rRNA
bacterial gene and gas chromatography were performed to quantify the microbiota and SCFA,
respectively.
In the BORICC Study, I observed significantly lower Firmicutes levels in participants with a
prior history of polyps (at greater CRC risk). There were no apparent effects of ageing or of
obesity on the microbiota when investigated at phylum or genus levels or on bacterial
diversity measures (alpha and beta diversity).
Faecal concentrations of acetate and of total SCFA were elevated in the older participants as
well as the obese participants in all studies. In BORICC Study, participants with a prior history
of adenomatous polyps and those who were obese had higher faecal propionate
concentrations. Concentrations of the branched-chain SCFA isobutyrate and isovalerate were
higher in stool from older people.
In summary, altered concentrations of faecal SCFA alterations were associated with ageing,
obesity and in those with a prior history of adenomatous polyps. However, there were no
associated effects on the abundance or diversity of gut bacteria
Investigation into vibration assisted micro milling: theory, modelling and applications
Get PDFPhD ThesisPrecision micro components are increasingly in demand for various engineering industries,
such as biomedical engineering, MEMS, electro-optics, aerospace and communications. The
proposed requirements of these components are not only in high accuracy, but also in good
surface performance, such as drag reduction, wear resistance and noise reduction, which has
become one of the main bottlenecks in the development of these industries. However,
processing these difficult-to-machine materials efficiently and economically is always a
challenging task, which stimulates the development and subsequent application of vibration
assisted machining (VAM) over the past few decades. Vibration assisted machining employs
additional external energy sources to generate high frequency vibration in the conventional
machining process, changing the machining (cutting) mechanism, thus reducing cutting force
and cutting heat and improving machining quality. The current awareness on VAM technology
is incomplete and effective implementation of the VAM process depends on a wide range of
technical issues, including vibration device design and setup, process parameters optimization
and performance evaluation. In this research, a 2D non-resonant vibration assisted system is
developed and evaluated. Cutting mechanism and relevant applications, such as functional
surface generation and microfluidic chips manufacturing is studies through both experimental
and finite element analysis (FEA) method.
A new two-dimensional piezoelectric actuator driven vibration stage is proposed and
prototyped. A double parallel four-bar linkage structure with double layer flexible hinges is
designed to guide the motion and reduce the displacement coupling effect between the two
directions. The compliance modelling and dynamic analysis are carried out based on the matrix
method and lagrangian principle, and the results are verified by finite element analysis. A
closed loop control system is developed and proposed based on LabVIEW program consisting
of data acquisition (DAQ) devices and capacitive sensors. Machining experiments have been
carried out to evaluate the performance of the vibration stage and the results show a good
agreement with the tool tip trajectory simulation results, which demonstrates the feasibility and
effectiveness of the vibration stage for vibration assisted micro milling.
The textured surface generation mechanism is investigated through both modelling and
experimental methods. A surface generation model based on homogenous matrices
transformation is proposed by considering micro cutter geometry and kinematics of vibration
assisted milling. On this basis, series of simulations are performed to provide insights into the
effects of various vibration parameters (frequency, amplitude and phase difference) on the
generation mechanism of typical textured surfaces in 1D and 2D vibration-assisted micro
milling. Furthermore, the wettability tests are performed on the machined surfaces with various
surface texture topographies. A new contact model, which considers both liquid infiltration
effects and air trapped in the microstructure, is proposed for predicting the wettability of the
fish scales surface texture. The following surface textures are used for T-shaped and Y-shaped
microchannels manufacturing to achieve liquid one-way flow and micro mixer applications,
respectively. The liquid flow experiments have been carried out and the results indicate that
liquid flow can be controlled effectively in the proposed microchannels at proper inlet flow
rates.
Burr formation and tool wear suppression mechanisms are studied by using both finite element
simulation and experiment methods. A finite element model of vibration assisted micro milling
using ABAQUS is developed based on the Johnson-Cook material and damage models. The
tool-workpiece separation conditions are studied by considering the tool tip trajectories. The
machining experiments are carried out on Ti-6Al-4V with coated micro milling tool (fine-grain
tungsten carbides substrate with ZrO2-BaCrO4 (ZB) coating) under different vibration
frequencies (high, medium and low) and cutting states (tool-workpiece separation or nonseparation). The results show that tool wear can be reduced effectively in vibration assisted
micro milling due to different wear suppression mechanisms. The relationship between tool
wear and cutting performance is studied, and the results indicate that besides tool wear
reduction, better surface finish, lower burrs and smaller chips can also be obtained as vibration
assistance is added
CD19+ B cells in early rheumatoid arthritis
Get PDFPhD ThesisBackground
Rheumatoid Arthritis (RA) is a genetically complex disease which causes inflammation
primarily affecting synovial joints. The therapeutic success of B cell depletion in RA has
confirmed the clinical relevance of B cells in disease, but their specific role in
pathogenesis remains unclear.
Aims
1. Identify differences in the transcriptome of CD19+ B cells between RA samples
and disease controls
2. Carry out an expression quantitative trait locus (eQTL) analysis of confirmed RA
genetic risk loci
3. Identify RA disease-specific eQTLs
4. Immunophenotype peripheral blood B cells
Method
242 patients were recruited, RNA and DNA was extracted for subsequent analyses and
parallel flow cytometry data obtained.
Results
A list of differentially expressed genes, without multiple test correction (MTC), was
identified between the transcriptome in RA and disease controls. Web-based analysis
tools identified downregulation of B cell receptor (BCR) signalling and pathways
involved in transcription and RNA processing in the RA group. A list of differentially
expressed genes (with MTC) was identified when samples were divided based on
chronological age and inflammatory status, not diagnosis. The eQTL analysis at RA risk
loci identified 10 cis eQTLs in B cells and a further 21 potential RA-specific eQTLs
which lay outside the known RA risk loci. The RA group had an increased frequency of
CD19+CD24hiCD38hi cells, a postulated regulatory subset
Conclusions
Age and inflammatory status have a greater influence on the CD19+ B cell transcriptome
than RA in this cohort. The genetic component to gene expression is highlighted by the
eQTL findings and will aid the prioritisation of genes for downstream functional work.
The disease-specific eQTLs identified may indicate novel mechanisms of disease. The
absence of a robust diagnostic gene signature between the disease groups examined may
relate to the heterogeneity of the B cells examined, as highlighted by differences in the
frequency of CD19+CD24hiCD38hi cells.Wellcome Trus
Effect of Agronomic Practices on Arbuscular Mycorrhizal Colonisation, Spore Density and Phosphorus Uptake in Spelt (Triticum spelta)
Get PDFPh. D. Thesis.Arbuscular mycorrhizae (AM) fungi form symbiotic, normally mutualistic, associations with
roots and can translocate nutrients, especially phosphorus (P) to the host plant. These fungi
can play an important role in agroecosystems, which is why it is important to understand how
agricultural practices and genotypes affect their existence and function.
There were three main components to this project. First, a systematic review of the literature
was carried out to document differences in AM fungal populations, diversity and colonisation
in crops grown in organic and conventional production systems; where possible, this included
meta-analyses of data extracted from the literature. In addition, two field experiments were
conducted. Experiment 1 (“fertiliser trial”) was conducted for two years (2014/15 and
2015/16) to find out the effect of spelt variety (Oberkulmer Rotkorn, ZOR, Rubiota and
Filderstolz) and fertiliser type (compost and mineral N) and rate (50 and100 kg N ha-1
) on
AM fungal colonisation in spelt roots, spore density in the soil and grain yield, P
(concentration, uptake and total) in straw and grain. Experiment 2 (“tillage trial”, 2015/16 and
2016/17) was designed to study the effect of crop protection management (conventional and
organic), fertiliser type (compost and mineral N), tillage system (minimum and conventional),
and spelt variety (Oberkulmer Rotkorn and Filderstolz) on the same mycorrhizal and crop
parameters. Both trials were conducted under field conditions at Nafferton farm in northeast
England.
Twenty studies were identified in the meta-analysis, with soil spore density, AM fungi
diversity, and root colonisation reported as indicators of AM fungal diversity and function.
Results from the fertiliser trial indicated that lower levels of fertiliser input promote vesicle
formation, while highest numbers of spores in 2015/16 were measured at high levels of
compost input. The tillage trial showed that crop protection had a significant effect on spore
density and was higher where organic approaches were used compared to conventional. Both
minimum tillage and compost fertilisation increased spore density, whereas, both
conventional tillage, and compost fertilisation enhanced AM fungal colonisation. Highest
spore densities were measured where the spelt variety was Oberkulmer, while AM fungal
colonisation was highest for Filderstolz.
The adoption of organic approaches could be a good strategy to encourage AM fungal
symbiosis especially using compost fertiliser. Selective breeding could also enhance the
ability of spelt to form symbioses with AM fungi, as shown for the variety Filderstolz.Ministry of Higher Education and
Scientific Research Ira
Below-ground impacts on microbial diversity of afforestation and woodland succession in Great Britain
Get PDFPhD ThesisWoodland restoration on farmland is gaining support as a method of habitat restoration and carbon sequestration. To understand the consequences of afforestation on soil microbial communities we require comparisons across agricultural, afforested, and established woodlands that differentiate changes in total soil diversity and diversity pertaining to soil functioning. I examine two natural-experiment, afforestation chronosequences describing changes to bacterial and fungal diversity in soils and on decomposing leaf litter using metabarcoding to identify taxa. The use and applications of metabarcoding are described in Chapter 1.
Chapters 2 and 3 report the abiotic and microbiological differences between agricultural and woodland soils over an afforestation and succession gradient. I study land use differences across 21 Woodland creation & Ecological Networks (WrEN) project sites – an afforestation chronosequence - with mixed-effect and multivariate models. The next chapters model how leaf litter decomposition (Chapter 4) and how decomposing litter associated microbes (Chapter 5) vary across woodland age categories (young, mature, and ancient) in 27 woodlands in the North East of England, across five tree species’ litter, during spring and summer.
In the first experiment I show key soil changes to carbon and nitrogen concentrations, and to C:N ratio across my afforestation gradient. I also demonstrate the rapid differentiation of woodland microbial communities from agricultural ones, with additional changes resulting from soil properties such as pH. In the second experiment I observe notable, but non-significant increases in decomposition in ancient woodland, as well as significant effects of species, sampling season, and woodland age on microbial diversity, beyond that of the changes expected from soil properties alone. In chapter 6 I discuss how these results integrate into the existing literature on the succession of decomposer communities over long timescales and their implications for woodland management. The work highlights the value of both afforestation and conservation of older woods.The Woodland Trus
Machine-Checked Formalisation and Verification of Cryptographic Protocols
Get PDFPhD ThesisAiming for strong security assurance, researchers in academia and industry focus
their interest on formal verification of cryptographic constructions. Automatising
formal verification has proved itself to be a very difficult task, where the main
challenge is to support generic constructions and theorems, and to carry out the
mathematical proofs.
This work focuses on machine-checked formalisation and automatic verification of cryptographic protocols. One aspect we covered is the novel support for
generic schemes and real-world constructions among old and novel protocols: key exchange schemes (Simple Password Exponential Key Exchange, SPEKE), commitment
schemes (with the popular Pedersen scheme), sigma protocols (with the Schnorr’s
zero-knowledge proof of knowledge protocol), and searchable encryption protocols
(Sophos).
We also investigated aspects related to the reasoning of simulation based proofs,
where indistinguishability of two different algorithms by any adversary is the crucial
point to prove privacy-related properties. We embedded information-flow techniques
into the EasyCrypt core language, then we show that our effort not only makes some
proofs easier and (sometimes) fewer, but is also more powerful than other existing
techniques in particular situations
Human-Centred Smart Buildings: Reframing Smartness Through the Lens of Human-Building Interaction
Get PDFPhD ThesisSmart buildings backed by data and algorithms promise reduced energy use and increased
value for businesses and occupants. Yet, this has typically been considered from an
engineering and systems perspective. Given increasing integration of sensing and
ubiquitous computing technologies in modern built environments, a growing HumanComputer Interaction (HCI) and Human-Building Interaction (HBI) community has begun
to advocate for the human-centred design of building technologies.
This dissertation argues that there is a need for an inclusive, socially just and sustainable
HBI agenda, to enable smarter buildings and facilities management. Deconstructing ‘smart’
rhetoric within HCI/HBI discourse and highlighting the values and ethics underpinning it, I
argue that existing approaches to ‘smartness’ privilege automation and efficiency over the
needs of human occupants. I undertake a qualitative inquiry into the roles of data and
digital technologies in human-centred smart buildings through three case studies:
i) How retrofitted environment sensors facilitate smarter energy auditing
practices. I contribute a methodology for using sensor toolkits in auditing,
technical design of the BuildAX sensing platform, and insights into sensoraugmented audits and how future standards might support these.
ii) How data and digital technologies foster collective experiences of thermal
comfort for office workers. I contribute a data elicitation interview method,
design of the ThermoKiosk experience survey system, and considerations for
integrating office tensions into workplace comfort management.
iii) How HBI can support agency and participation in the everyday management
and adaptation of a contemporary smart building. I contribute a ‘building walks’
method to elicit conversations on the future of building technologies, new
understandings of how student occupants conceptualise and evaluate spaces,
and how buildings of the future might better enable occupant agency.
Through these, I contribute a re-framing of smartness to be more human-centred, including
concerns for collaboration, inclusion, and human decision-making which does not consider
occupants a ‘problem’ to be solved. The results of the case studies are synthesised into a set
of six principles for the design of technology within human-centred smart buildings, re-grounding the field of HBI in the philosophy of environmental and social justice
Confronting the shadow : a power electronics praxis
Get PDFPh. D. ThesisConfronting the Shadow is a practice-led research project based on composition and recording in the Power Electronics music modality. The submission comprises seven albums and a written thesis.
Power Electronics is a confrontational form of music practice situated within the noise music genre. The purpose of the research is to use this modality as a vehicle for exploring relations between noise, the urban space and mental health. As practice-led research, these relations are accounted for in a written thesis that has been structured to support and map the recorded material. The discursive methodology described by Somerville as postmodern emergence is employed to describe how the ideas and arguments made in the thesis component have emerged from the process of creating the portfolio. Key ideas incorporated in this manner throughout the thesis are adapted from the psychoanalytic works of Carl Gustav Jung, in particular his confrontation with the shadow.
Jung’s ideas are explored in conjunction with material from musicology (Hegarty, Novak, Keenan, Attali), social policy (Barham, Moon, Kearns & Joseph, Laurance, the Schizophrenia Commission, Rethink Mental Illness), psychogeography (Sinclair, Raban, Vidler, Coverley), psychology (Laing & Esterson), film studies (Balsom & Peleg, Rabiger), and more, to create a nuanced multidisciplinary mapping of the portfolio and its interrogation of noise, the urban space and mental health. Emphasis is placed on the context of deinstitutionalisation – the socio-cultural and political transfer of mental healthcare from institutions to the community in the late 20th century – that transformed the experience of both the urban space and mental illness in this period.
The portfolio and its supporting discourse explore the role that different kinds of creative practice such as music and film play in the generation and mediation of ideas and attitudes towards mental illness and its care, and demonstrate how the conclusions drawn from this analysis have informed the continuing development of the practice in consequence
“We don’t have a collection, just an art gallery”: An enquiry into the origins, rationale and role of the Hatton Gallery Collection formed by Professor Lawrence Gowing for King’s College, University of Durham, from 1952 to 1957
Get PDFPh. D. Thesis.This thesis examines the formation of a collection of old master and contemporary
art works by Professor Lawrence Gowing for the Hatton Gallery in the Fine Art
Department of King’s College, Durham University, between 1952 and 1957. This
collection was the foundation of what is now understood as the “teaching collection”.
Through the exploration of archives, texts and narratives, this study considers the
origins of the collection’s formation and the rationale for its content. It also
addresses the question of its role within the pedagogy of the Department, in which
Richard Hamilton and Victor Pasmore were concurrently developing an
experimental basic course and installing unorthodox exhibitions in the Hatton
Gallery.
This thesis argues that two significant factors converged to bring about the
formation of the art collection. The first was the sequence of events that established
the Fine Art Department within a university institution and brought Gowing to
Newcastle; the second was Gowing’s ambition as an educator. This research
particularly draws on Gowing’s writings to argue that this was predicated on his own
desire to understand the motivations of the artist and to share his own experience of
making and looking at art with others. Rather than a narrative based on radical
pedagogy, this thesis therefore refocuses the attention onto Gowing’s pedagogic
activities within the Fine Art Department, which have been overlooked in contrast to
those of other staff, particularly Hamilton and Pasmore. It thereby offers a fresh
perspective on the development of progressive pedagogical ideas at King’s College
and the influence of this institution on art education.
In so doing, this thesis makes a valuable contribution to the field of art history and
creative arts pedagogy and concludes with propositions for the use and purpose of
the Hatton Gallery Collection in the twenty-first centuryArts and Humanities Research
Council (AHRC
The past and future impact of ice tongue loss on outlet glaciers in northern Greenland
Get PDFPh. D. Thesis.Ice discharge from fast-flowing outlet glaciers across the Greenland Ice Sheet (GrIS)
has increased in response to 21st century climate warming. These outlets are sensitive to
changes at their terminus, particularly iceberg calving from floating tongues. Many glaciers
have accelerated and thinned in response to recent retreat, but the impact of major calving
events and ice tongue loss on ice discharge and sea level rise remains poorly constrained.
Northern Greenland is the last region with floating ice tongues, but remains understudied
compared to other regions of the ice sheet. The aim of this thesis is to quantify outlet
glacier change across northern Greenland and assess the role of ice tongues in modulating
past and future glacier dynamics. To address this aim I use: i) remote sensing to assess
past glacier change across northern Greenland, and ii) two sets of numerical modelling
experiments to simulate future ice tongue loss at Petermann Glacier. The key findings are
that outlet glacier retreat rates have increased in the last two decades, but the dynamic
response to retreat was dependent on terminus type (grounded vs floating) and glacier
geometry. Grounded outlet glaciers retreated, accelerated and thinned, while the response
of glaciers with ice tongues was more varied, and dependent on tongue confinement and
bed topography inland of the grounding line. Modelling experiments on Petermann Glacier
further corroborate these findings, demonstrating that unconfined portions of the tongue
had little impact on dynamics, but removing confined sections closer to the grounding line
accelerated ice flow. However, the long-term response (up to 100-years) to ice tongue loss
was muted by the absence of a retrograde bed-slope in the grounding zone, which limited
grounding line retreat. Overall, this thesis highlights the complexity of outlet glacier
behaviour in northern Greenland. It also notes the variability between individual glacier
responses to ice tongue loss. These factors require careful consideration when assessing
future glacier sensitivity to ice tongue/shelf loss in both Greenland and Antarctica in order
to accurately project accelerated ice discharge and ultimately global sea level rise.IAPETUS Doctoral Training Partnership. British Antarctic Surve