5357 research outputs found
Sort by
Mitophagy and the dynamics of mitochondrial DNA inheritance in early development and reproduction
Get PDFPh. D. Thesis.Inherited heteroplasmic mitochondrial DNA (mtDNA) mutations are a cause of severe disease
of adults and children. Thus, methods have been developed to reduce inheritance of
pathogenic mtDNA variants; preimplantation genetic diagnosis (PGD) and pronuclear transfer
(PNT). However, it is unclear at which stage of development a biopsy better predicts embryo
heteroplasmy in PGD. Meanwhile, a small amount of pathogenic variant-harbouring mtDNA is
carried over during PNT.
Recent work indicates that embryos undergo mitophagy during late preimplantion
development. This coincides with a reported increase in intercellular variation of mtDNA
heteroplasmy, raising the question of whether mitophagy contributes to segregation of mtDNA.
In addition, manipulation of mitophagy may be applied to reduce carry-over of mtDNA variants
during PNT.
To investigate the mechanisms of mitophagy, using a large single cell RNA sequencing data
from human embryos, I analysed the expression of key mitophagy genes. BNIP3 family genes
were identified as probable mediators of mitophagy. Overexpression of a phosphomimetic
BNIP3L protein upregulated mitophagy, which may be useful in preventing survival of carried
over mtDNA in PNT. Furthermore, correlations emerged between mitophagy genes and genes
driving the establishment of cell lineages in the blastocyst, suggesting lineage-specific
regulation of mitophagy.
Using the tRNAalanine (tRNAala) mouse model carrying a pathogenic mtDNA variant, I
verified an increase in intercellular variation of heteroplasmy in the blastocyst. Analysis of the
segregation of mtDNA suggested that the 8-cell embryo is the optimal stage for PGD biopsy.
Upregulation of mitophagy had no detectable influence on the segregation of mtDNA,
suggesting that mitophagy may not be a major source of intercellular variation in heteroplasmy.
I also revealed an accumulation of mtDNA variants in the oocytes of aged tRNAala mice.
Combined with the presence of a pathogenic mutation, mtDNA variants did not manifest a
selection mechanism. This suggests acquired mtDNA variants only modestly impair the health
of aged oocytes and age-related loss of fertility is primarily due to other causes.
These findings elucidate mechanisms which may modulate the inheritance of mtDNA in early
development. Furthermore, they provide insight into the impact of mitophagy in the
preimplantation embryo, and identify an 8-cell embryo biopsy as preferable to that of a
blastocyst in predicting embryo heteroplasmy during PGD. Identification of a method to
upregulate mitophagy will help guide the process of preventing the inheritance of mtDNA
mutations using PN
The balance between predators and prey in a mixed seabird colony: managing biodiversity and the conservation of rare species
Get PDFPh. D. ThesisIncreases in seabird population sizes on islands, resulting from reduced mortality and/or
increased reproductivity, has resulted from the control of avian predators when predation was
confirmed to be the main driver of seabird decline. A substantial conflict in conservation
management arises when the control operation targets a protected predator. Tensions and
divisions between regulators and conservation managers can be exacerbated when the prey
species is of high conservation concern. This latter situation underpins this research study based
on Coquet Island, UK, where the core of conservation management is targeted at mitigating
predation on Roseate Tern (RT) by breeding Large Gulls (LG), represented by Lesser Blackbacked Gull Larus fuscus (LBBGU) and Herring Gull L. argentatus (HGU). In recent years,
the conservation status of HGU has changed to red and LBBGU to Amber categories in the
light of increasing concern of notable decline for unknown reasons in the UK. Hence, it is
important to have evidence on which to base management strategies for conserving Roseate
Terns which minimises the conservation conflicts between prey and predators, all of which are
of conservation concern.
A complete understanding of predator-prey relationships relies on determining the dynamic
stability of prey and predator populations, and how the food web containing predator-prey pairs
responds to environmental influences and other indirect effects. This research investigates the
main drivers of LG predation activity over the RT colony during the breeding season. A
particular dilemma in estimating the impact of predation by breeding LG on the Coquet Island
RT colony resulted from the presence of loafing LG, either non-breeding subadult birds or birds
from other colonies, using the intertidal area around the island. Therefore, to test the hypothesis
that LG breeding on the island also used the island’s seabird colonies as a foraging resource,
indirect (Camera traps and dietary analysis of LG pellets) and direct (Observation of predation
activity, foraging range estimation from tracking technologies) methods were used.
The results of this study suggest that the frequency of LG events over the RT colony increased
towards the end of the breeding season in relation to the number of loafing LG in the intertidal
area, and was influenced by tidal state and decreased during the period of RT chick biomass
availability. This study provided evidence that LG breeding on the island also used the reserve
as part of their foraging territory. The outputs of the tracking data were compatible with the
outputs of the pellet analyses which showed a high utilization of available prey from the reserve.
LG on Coquet Island utilizing all types of prey sources with no difference between of breeding
or roosting LG with respect to the range of prey types. Indirect evidence that LG predation
would be a threat to the small colony of RT was based on the finding that other tern species
nesting on Coquet Island were identified using combined molecular and morphological
techniques as prey in LG pellets collected from the breeding and roosting LG on Coquet Island.
In addition, a study of laser hazing carried out as part of the thesis work shows that this is an
efficient non-lethal deterrent for LG management on Coquet Island. Overall, the results of this
study provide evidence showing how small numbers of LG may be allowed to breed on Coquet
Island by managing the timing of their breeding in relation to the arrival and breeding of RT,
and by efficient deterrence of loafing, non-breeding birds. Such an approach will facilitate a
wider understanding of how to resolve conservation conflicts between protected predator and
protected prey species.LIFE programm
Biologically mediated abiotic degradation (BMAD) of chlorinated solvents using Fe-bearing clay minerals
No full textPh. D. Thesis.Chlorinated solvents, such as tetrachloroethene (PCE), trichloroethene (TCE), and trihalomethanes
(THMs), are extremely persistent and widespread groundwater contaminants. Due to
their ecotoxicological and physiochemical properties, chlorinated solvent contamination poses
a major threat to the quality of safe potable groundwater. Bioremediation is often employed
for sites requiring a low-cost long-term remediation scheme to transform these pollutants to
lesser chlorinated products. Whilst many studies have shown successful removal of PCE and
TCE to a certain extent, bioremediation often stalls at cis-DCE and vinyl chloride (VC), which
are much more toxic than either PCE or TCE and requires specific bacterial assemblages to
remove. Alternatively, the abiotic degradation pathway, for example in the presence of minerals,
favours the conversion of PCE and TCE to benign C2 gases. Fe-bearing clay minerals are
seen as a promising choice of mineral for abiotic degradation because of their resistance to
dissolution and ubiquity in the subsurface, which make them a sustainable source of reduction.
Furthermore, interactions between aqueous Fe(II) and aqueous S(-II), which is produced via
microbial activity, and structural Fe(III) bound inside clay minerals leads to the formation of
an electron-doped clay mineral which can be used to reduce contaminants. However, electron
transfer from aqueous Fe(II) or S(-II) also leads to the formation of solid oxidation product(s),
with their exact nature and identity causing some controversy, with recent work suggesting the
formation of nanocrystalline mixed valent Fe phases such as green rust, which, in turn, could
contribute to contaminant transformation as potential reactive mineral intermediates (RMIs).
Here we evaluated the reactivity of Fe-bearing clay minerals toward the reductive degradation
of PCE, TCE, and THMs. We compared the reactivity with dithionite-reduced clay minerals
and for high and low Fe content clay minerals (nontronite, NAu-1; montmorillonite, SWy-2), to
modulate the clay mineral Fe(II) concentration, and varied the concentrations of aqueous Fe(II)
or aqueous S(-II) to investigate the effect the concentration of each aqueous species has on the
identity and potential reactivity of any RMIs that may form. We also used a separate reactive
probe, hexachloroethane (HCA), which follows the same reductive -elimination reaction
mechanism as the abiotic degradation pathway PCE and TCE follows, to further investigate
any differences in the Fe-bearing RMIs reactivity towards degrading recalcitrant contaminants.
We complemented our reactivity studies with techniques to identify any RMIs and used a
combination of 57Fe-Mössbauer spectroscopy and X-ray diffraction (XRD).
Transformation of PCE and TCE was not observed when NAu-1 (20 wt% Fe) or dithionitereduced
SWy-2 (2.5 wt% Fe) was present, suggesting that clay mineral structural Fe(II) alone
was not capable of reducing PCE and TCE. Similarly, we found no detection of any PCE or TCE
transformation products from any of our experimental conditions when Fe-bearing clay minerals
were reduced using aqueous S(-II), and also found no detectable transformation products
from our THMs degradation study. Interestingly, PCE and TCE transformation products
(acetylene, ethene, and ethane) were detected only in reactors containing SWy-2 amended
with 20 mM aqueous Fe(II). We found from our experiments using HCA that the reactivity of
HCA is dependent on both the clay mineral Fe content, as well as the initial aqueous Fe(II)
concentration used. We believe that the rate of HCA removal is affected by the precipitate
that is formed, with the reactivity of the precipitate dependent on the Fe stoichiometry and
the mineral phase that has formed.
Mössbauer spectroscopy was used to identify the Fe stoichiometry of both the structural
clay mineral Fe as well as any Fe-bearing precipitates that formed. In the case of Fe(II)-reduced
clay minerals, Mössbauer shows that both precipitates that form in the presence of 20 mM
Fe(II) have similar amounts of Fe(II) present (NAu-1: 80.9%; SWy-2: 82.9%), the ratio
of Fe(II) bound in the precipitate relative to the clay mineral Fe total is far greater when
SWy-2 is present compared with NAu-1 ( 4.3 vs 0.5 for 20 mM amended SWy-2 and NAu-1
respectively). XRD analysis has shown that the precipitate formed for 20 mM amended SWy-2
bears some resemblance to a 1:1 trioctahedral Fe-silicate, yet hyperfine parameters from
Mössbauer spectroscopy show Fe(III) coordination for a 2:1 trioctahedral mineral. The reverse
appears to be true in the case of S(-II)-reduced clay minerals, where on visual inspection
precipitates only appeared to form when NAu-1 was present, but due to the limitations of
Mössbauer spectroscopy and XRD on identifying RMIs, it was difficult to confirm the identity
of these Fe-S precipitates.
Overall, while we have evaluated that Fe-bearing clay minerals may not play a pivotal role in
the reductive degradation of chlorinated solvents, we have highlighted the potential importance
of RMIs in the subsurface as contributors to abiotic natural attenuation, with the composition
and identity of RMIs that form due to interfacial electron transfer being strongly controlled by
aqueous Fe(II) or S(-II) concentrations and clay mineral Fe content. The formation of these
RMIs from interfacial electron transfer can also provide further insight into Fe-bearing mineral
formation throughout geological history such as the formation of low-Fe(III) greenalite
Britain and the Falklands : International Perspectives 1982-1990
Get PDFPh. D. Thesis.The Falklands dispute revolved around a group of small islands, the sovereignty of which
was claimed by two nations. However, once conflict broke in April 1982, the dispute took
an international dimension. States were drawn in by their relationships with Britain and
Argentina. This thesis seeks to examine to what extent there was an international reaction to
the crisis and offer a comparison between the international reactions to the dispute, seeking
to draw common themes, and thus offers a comparative history of international receptions
to the conflict. Although, the Falklands conflict has been covered in depth in both academic
and other text, the historiography lacks a detailed survey of the international response. In
presenting a comparative study of international reactions to the dispute, this thesis
contributes to understanding to what extent the ‘Falklands Factor’, the phenomenon in
Britain that boosted support for the Conservative government, was a shared phenomenon
elsewhere in the world.
This study examines nations in a number of different international organisations and
assesses the influencing factors behind their reaction to the crisis. Although these
organisations held much power and influence, their ability to wield such influence was
limited in how the situation was viewed by the individual member states. The groups
examined in this thesis were all formed out of individual nations that at some point held a
shared ethos or goal which encouraged them to come together in the form of governmental
coalition. However, in a bipolar world, the individual components that made up the
collective, often prioritised their own objectives over those of the organisation. The conflict
and subsequent debates highlighted how this phenomenon not only affected international
response to the Falklands crisis but how it could also influence relations between states.
Although the conflict has been covered in detail, it has in the main been looked at in a
national and exceptionalist context. This work offers a transnational perspective through
comparison between different reactions in states, offering a contribution to our
understanding of the crisis’ impact.Masonic Charitable Fun
Synthesis and biomedical applications of fluorescent organophosphorus compounds
Get PDFPhD ThesisAn important and ongoing area of research is the treatment and imaging of diseases such as
cancer and heart disease, as these are two of the leading causes of death worldwide. Prior
research in this area has led to the development of effective agents such as the
chemotherapeutic agent, cisplatin, and Myoview, a cardiac perfusion imaging agent.
However, with the number of cases of cancer and heart disease continuing to rise, there is still
an urgent requirement for further development of these agents. Thus, the synthesis of
effective imaging agents and, in particular, probes with multiple modalities which can harness
the benefits of multiple imaging techniques are of interest. Organophosphorus compounds
provide a versatile platform to build such probes that could be applied in fluorescence
imaging, SPECT, PET and MRS. Therefore, this thesis explores the functionalisation of
organophosphorus compounds to afford a range of novel, fluorescent, phosphine probes with
potential medicinal applications.
Auranofin is a triethylphosphine containing, FDA approved therapeutic agent that has recently
shown potential for its repurposing in new areas including neurodegenerative disorders,
parasitic infections, HIV and cancers. Thus, Chapter 2 explores the synthesis of a series of
analogues of auranofin by altering the triethylphosphine ligand. A series of fluorescent
analogues of auranofin are also introduced which may hold potential as theranostic agents
and perhaps aid in the derivation or elucidation of the mechanism of action of the
pharmaceutical.
Azacycles are nitrogen containing cyclic compounds which are commonly found in natural
products and bioactive compounds. Chapter 3 introduces three novel fluorescent
phosphacycles which are far less studied than their nitrogen derivatives. We investigate a
highly strained three-membered cycle, a phosphirane, where we explore its air- and thermalstability and its coordination to group 6 metal carbonyl complexes. The methylation of the
phosphirane to afford a phosphiranium salt is detailed for which the product has potential
application as a dual optical and magnetic resonance imaging agent.
We also look briefly at two six-membered 1,3,5-diazaphosphinanes, which were synthesised
in collaboration with Dr Randolf Köhn, at the University of Bath are detailed. Coordination of
one of the diazaphosphinanes to chromium(III) centres and the subsequent preliminary
experiments to test for its application in catalytic 1-hexene trimerization will then be
described. A short collaborative project with Professor Bill Henderson at the University of
Waikato is introduced to detail how one of the fluorescent phosphines can be applied in the
fluorescent labelling of amine modified surfaces.
The final phosphacycles introduced are the seven-membered phosphacycles, the
phosphepines. The synthesis of two group 6 phosphepine complexes will be described
followed by a study of their electronic properties. Preliminary experiments were then carried
out in an effort to afford the free ligand which would allow for its further functionalisation.
Chapter 4 describes the synthesis of BodP3, a fluorescent tridentate phosphine, via a platinumcatalysed hydrophosphination of the fluorescent primary phosphine. Exploration into its
coordination to group 10 metals will be detailed, with particular attention focused on the
square planar platinum complexes as potential theranostic agents.
Combined imaging agents are becoming increasingly popular in order to harness the benefits
of multiple imaging techniques, such as optical imaging and radioimaging, to overcome the
limitations of the individual techniques. Thus, Chapter 5 introduces a series of phosphonium
salts which have potential as trifunctional imaging agents. These novel phosphonium salts
contain i) a fluorescent Bodipy backbone suitable for in vitro fluorescence imaging, ii) a
positively charged phosphonium centre to enable specific localisation within the
mitochondria, and iii) an alkyne functional group to enable radiolabelling by click chemistry to
facilitate in vivo PET imaging. Finally, preliminary click chemistry reactions will be described to
demonstrate the synthesis of a cold standard of this trifunctional imaging agent
High Power Density Propulsion Motor for Hybrid Electric Aircraft
Get PDFPh. D. Thesis.The Civil Aerospace is looking ahead for new solutions that can offer further significant improvement in aircraft efficiencies and emissions. Hybrid Electric Distributed Propulsion (HEDP)
aircraft’s configurations have been extensively modelled, and these results show it is possible to
obtain notable benefits with some authors claiming that overall fuel savings of more than 70% are
possible compared with today’s designs. However, these models depend critically on electrical
power networks and machines being able to operate with significantly improved power densities
and efficiencies in the aircraft electric plant. In general these multi-megawatt power systems have
been used in applications where volume and weight have been secondary considerations and
hence new techniques and approaches are now required. A further issue is designing machines
to address other constraints required for aircraft installation, for example motors integrating with
propulsive systems.
Hence for these applications new and evermore performing electrical machine designs are now
required. The work showcased in this thesis is meant as a beginning to address these new
requirements.
Chapter 1 presents the challenges identified and locates the motivation of this work in the more
vast application sense of aerospace propulsion. Chapter 2 provides a literature review and
initial considerations on the power density increase. Chapter 3 is a collection of methodologies
developed for mainly mechanical and initial electromagnetic performance evaluation. Chapter 4
delivers the optimized result for different machines comparison as well as alternative choices of
objectives and constraints dictated by the design envelope. Chapter 5 identifies and develops
further the chosen candidate: high order effects in the mechanics/rotor-dynamics and rotor losses
estimation are thoroughly investigated. Chapter 6 addresses the manufacture choices undertaken
and initial tests conducted on the machine. The thesis ends with the conclusions in Chapter 7
Deep language learning at a distance : Investigating the efficacy of a low-cost blended intervention in the small rural primary schools of Greece
Get PDFPhD ThesisThe present research evaluates the impact of a blended remote learning intervention on the
English as a Foreign Language attainment of 8-12-year-old children living in rural parts of
Greece who, contrary to their urban counterparts, have no access to English language
instruction in their schools. Most of the research on blended learning to date has been
carried out in the context of higher and secondary education, and thus little is currently
known about the practical feasibility and the parameters that might facilitate or impede
academic success in a blended learning environment involving primary school children.
Furthermore, there has been little systematic attention to the effectiveness of such
educational interventions in low-income and resource-scarce settings. Importantly, this
thesis moves beyond treating technology as a means by which to simply provide access to
automated versions of conventional models of teaching, thus conceptualising ‘quality
language learning’ as personalised, participatory, collaborative, guided learning, and deep
content.
An embedded mixed methods design was used in this study. The primary aims of the
research were addressed through a quasi-experimental design. Across eight small rural
primary schools, forty-seven children accessed the intervention for forty-five minutes per
week over 12 weeks. Additional data were collected, including qualitative semi-structured
headteacher and parent interviews, children focus groups and informal observations, to
further illuminate factors affecting outcomes.
The intervention was established as a significant predictor of gains in three out of five
language areas assessed (vocabulary, grammar, and aural comprehension). Evidence from
the qualitative strand regarding factors at the intervention level, teacher attributes, and
individual child factors that appear to have influenced outcomes are discussed. On the basis
of the findings of the present research, a model is proposed of the potential mechanisms
underpinning the efficacy of the intervention within the intended contexts, accounting for
individual differences and implementation factors.The A.G. Leventis Foundatio
Performance-efficient cryptographic primitives in constrained devices
Get PDFPhD ThesisResource-constrained devices are small, low-cost, usually fixed function and very limitedresource devices. They are constrained in terms of memory, computational capabilities,
communication bandwidth and power. In the last decade, we have seen widespread use of
these devices in health care, smart homes and cities, sensor networks, wearables, automotive
systems, and other fields. Consequently, there has been an increase in the research activities
in the security of these devices, especially in how to design and implement cryptography that
meets the devices’ extreme resource constraints.
Cryptographic primitives are low-level cryptographic algorithms used to construct security protocols that provide security, authenticity, and integrity of the messages. The building
blocks of the primitives, which are built heavily on mathematical theories, are computationally complex and demands considerable computing resources. As a result, most of these
primitives are either too large to fit on resource-constrained devices or highly inefficient
when implemented on them.
There have been many attempts to address this problem in the literature where cryptography engineers modify conventional primitives into lightweight versions or build new
lightweight primitives from scratch. Unfortunately, both solutions suffer from either reduced
security, low performance, or high implementation cost.
This thesis investigates the performance of the conventional cryptographic primitives and
explores the effect of their different building blocks and design choices on their performance.
It also studies the impact of the various implementations approaches and optimisation
techniques on their performance. Moreover, it investigates the limitations imposed by the
tight processing and storage capabilities in constrained devices in implementing cryptography.
Furthermore, it evaluates the performance of many newly designed lightweight cryptographic
primitives and investigates the resources required to run them with acceptable performance.
The thesis aims to provide an insight into the performance of the cryptographic primitives and
the resource needed to run them with acceptable performance. This will help in providing
solutions that balance performance, security, and resource requirements for these devices.The Institute of
Public Administration in Riyadh, and the Saudi Arabian Cultural Bureau in
Londo
Essays in banking, credit and the macroeconomy
Get PDFPhD ThesisOver the last two decades, banks have become increasingly large and interdependent due to the
ongoing process of globalization of international trade and finance, as well as the advent of a wide
range of technological advances that have made financial services more easily accessible to the
public. These developments in the banking sector translate into more credit availability in the
financial system. Credit availability is essential for households and firms’ financing and investment
decisions with potential direct effects on economic growth. On this regard, scholars agree that while,
on the one hand, a sustainable credit expansion can foster economic growth, on the other, such
expansion can undermine financial stability if not properly handled. Thus, the magnitude and time
dynamics of credit aggregates pose significant policy challenges for policy-makers. This thesis
contributes to the ongoing debate on the nexus between banking and the real economy, in the attempt
of leaping forward in the quest of causality between finance, stability and growth.
In Chapter Two, we investigate the link between shocks originating from the banking sector
and aggregate leverage, as measured by the credit-to-GDP gap. Using a balanced panel of 15
advanced countries for the period 1989-2016, we build on the Granularity Hypothesis and investigate
banking granular shocks, based on balance sheet data of large banks, as an indicator of banking
distress. Using methods that account for potential endogeneity between the real and financial sectors,
we find that banking shocks Granger-cause aggregate leverage risk. In particular, banking shocks
tend to increase the level of leverage and cause departures of the credit-to-GDP ratio from its long term trend. This result highlights the importance of closely scrutinising how the lending activities of
large banks evolve, as the cohort of large banks is capable of moving upward/downward overall
leverage of the entire financial systems.
In Chapter Three, we first uncover the time series properties of private credit in a panel factor
model of 12 Eurozone and 8 non-Eurozone European countries and find evidence of credit
convergence. We then focus on the first principal component of total credit, credit-to-GDP ratio, and
credit-to-GDP gap series, and find the occurrence of long-run relationships between the latter and
measures of ECB’s unconventional monetary policy, such as total assets and the shadow interest rate.
Such a relationship is robust even after accounting for multiple structural breaks in the data. Within
a structural factor augmented VAR (SFAVAR) approach, shocks to the above unconventional
monetary policy variables are found to be positively related to the common factor of total credit,
which we take as evidence on the transmission mechanism of UMP through the credit channel.
In Chapter Four, we examine the factor structure of private and public debt for a cohort of 22
advanced economies over the period 2000-2019. We control for cross-sectional dependence in the
panel data using a principal component approach, where we also disentangle the data into unobserved
common factors and idiosyncratic components. Using methods that account for the long- and short run dynamics and potential endogeneity, as well the presence of cross-sectional dependence, we shed
light on the heterogeneous behaviour across credit types and countries. Empirical results show that
common factors affect the causality in the credit-growth nexus
Novel computational approaches to research longitudinal microRNA-mRNA expression datasets
Get PDFPh. D. Thesis.microRNAs (miRNAs) regulate many biological processes and are used as biomarkers for
the classification of diseases, conditions and developmental stages. miRNAs function by
targeting and negatively regulating specific mRNAs. One limitation of utilising miRNAs in
experimental work is the complex and often redundant behaviour of miRNA-mRNA interactions; as a single miRNA can regulate many mRNAs and one mRNA can be regulated
by multiple miRNAs. This complexity stifles the potential of miRNAs. However, miRNAmRNA expression datasets are becoming generated more frequently and they can help to
garner greater understanding of how miRNAs regulate biological systems. Furthermore,
researchers are generating longitudinal datasets as these can elude to greater understanding of how biological conditions change over time. Thus there is a rise of longitudinal miRNA-mRNA expression datasets. However, extracting useful information from
increasingly sophisticated datasets is a challenge in biological research. Exploration of
such datasets using computational techniques, such as big data bioinformatics, kinetic
modelling and machine learning could help in identifying interesting miRNA-mRNA interactions. During this PhD I asked if these methodologies can be used to gain insights
from a range of longitudinal miRNA-mRNA expression datasets. Hence, I developed an
R/Bioconductor tool called TimiRGeN to integrate, analyse and generate small networks
from longitudinal miRNA-mRNA datasets. Datasets from kidney fibrosis, chondrogenesis dataset, breast cancer and Huntington’s disease (HD) were analysed with TimiRGeN.
Results from the chondrogenesis dataset analysis were taken forward to generate a multimiRNA kinetic model. With help from my collaborators this model was validated and predictions were made. Using the HD dataset, machine learning (ML) techniques trained
models to detect if samples have disease or wild type conditions. Overall, I have developed and used multiple computational techniques to increase knowledge gained from
longitudinal miRNA-mRNA datasets, and I believe the results show these techniques can
contribute to miRNA research