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Advanced modelling and design considerations for interconnects in ultra- low power digital system
Get PDFPhD ThesisAs Very Large Scale Integration (VLSI) is progressing in very Deep
submicron (DSM) regime without decreasing chip area, the importance
of global interconnects increases but at the cost of
performance and power consumption for advanced System-on-
Chip (SoC)s. However, the growing complexity of interconnects
behaviour presents a challenge for their adequate modelling,
whereby conventional circuit theoretic approaches cannot provide
sufficient accuracy. During the last decades, fractional differential
calculus has been successfully applied to modelling
certain classes of dynamical systems while keeping complexity
of the models under acceptable bounds. For example, fractional
calculus can help capturing inherent physical effects in electrical
networks in a compact form, without following conventional
assumptions about linearization of non-linear interconnect components.
This thesis tackles the problem of interconnect modelling in
its generality to simulate a wide range of interconnection configurations,
its capacity to emulate irregular circuit elements
and its simplicity in the form of responsible approximation. This
includes modelling and analysing interconnections considering
their irregular components to add more flexibility and freedom
for design. The aim is to achieve the simplest adaptable model
with the highest possible accuracy. Thus, the proposed model
can be used for fast computer simulation of interconnection
behaviour. In addition, this thesis proposes a low power circuit
for driving a global interconnect at voltages close to the noise
level. As a result, the proposed circuit demonstrates a promising
solution to address the energy and performance issues related
to scaling effects on interconnects along with soft errors that
can be caused by neutron particles.
The major contributions of this thesis are twofold. Firstly, in
order to address Ultra-Low Power (ULP) design limitations, a novel
driver scheme has been configured. This scheme uses a bootstrap
circuitry which boosts the driver’s ability to drive a long
interconnect with an important feedback feature in it. Hence,
this approach achieves two objectives: improving performance
and mitigating power consumption. Those achievements are essential
in designing ULP circuits along with occupying a smaller
footprint and being immune to noise, observed in this design as
well. These have been verified by comparing the proposed design
to the previous and traditional circuits using a simulation tool.
Additionally, the boosting based approach has been shown beneficial
in mitigating the effects of single event upset (SEU)s, which
are known to affect DSM circuits working under low voltages.
Secondly, the CMOS circuit driving a distributed RLC load has
been brought in its analysis into the fractional order domain. This
model will make the on-chip interconnect structure easy to adjust
by including the effect of fractional orders on the interconnect
timing, which has not been considered before. A second-order
model for the transfer functions of the proposed general structure
is derived, keeping the complexity associated with second-order
models for this class of circuits at a minimum. The approach
here attaches an important trait of robustness to the circuit
design procedure; namely, by simply adjusting the fractional
order we can avoid modifying the circuit components. This can
also be used to optimise the estimation of the system’s delay
for a broad range of frequencies, particularly at the beginning
of the design flow, when computational speed is of paramount
importance.Iraqi Ministry of Higher Education
and Scientific Researc
Exploring the Effects of Bile Acid Inhibition in Cholestatic Pruritus
Get PDFPh. D. Thesis.Pruritus (itch) is an important symptom associated with cholestatic liver diseases. The aim of this
work was to study cholestatic pruritus to further our understanding of the prevalence in primary
biliary cholangitis (PBC) and explore the role of inhibiting circulating bile acids (BAs) in
relieving cholestatic pruritus.
The cross-sectional study of pruritus from over 2800 patients from the UK-PBC research cohort
showed that prevalence of pruritus in PBC is high (74%) with a significant proportion of patients
reporting severe itch during the course of their disease. This study also highlighted the undertreatment of itch with inadequate use of guideline recommended drugs in the UK.
The impact of inhibiting circulating BAs on cholestatic pruritus was studied in two different
ways- i) via nasobiliary drainage (NBD, i.e. external diversion of bile and BAs away from the
ileum), and ii) via pharmacological inhibition of the ileal bile acid transporter (IBAT) that
mediates enterohepatic circulation of BAs. The retrospective cohort study of NBD showed the
intervention is a highly effective treatment, but only of short-term durability and associated with
high complication rate. The phase 2 clinical trial of GSK2330672, a human IBAT inhibitor agent,
showed that two-weeks of treatment significantly reduced pruritus severity compared to placebo.
The metabonomic and microbiome studies explored the serum metabonome and gut microbiota
profile of pruritus in PBC. In addition, the effects of GSK2330672 on metabonome and gut
microbiome were investigated. The study demonstrated that pruritus in PBC is associated with
elevated serum total and glyco-conjugated BAs but no gut bacterial dysbiosis. Also,
GSK2330672 was shown to reduce all taurine and glyco- conjugated serum BAs, increase faecal
BAs and alter the gut-microbial composition.
Taken together, the research studies presented in this thesis suggest: i) high prevalence of pruritus
and its under-treatment in PBC, ii) removal of BAs by NBD or inhibition by IBAT inhibitor drug
improves cholestatic pruritus and, iii) serum BAs but not gut microbiome are altered in
cholestatic pruritus and they can be modified by IBAT inhibitor treatmentNational Institute for
Health Research (NIHR), Newcastle Biomedical Research Centre (BRC
Early Modern Utopian Writings and the Just Commonwealth
Get PDFPhD ThesisThis thesis sets out to examine the interplay between utopian theory and political practice through
close readings of three key texts in the early modern Western utopian tradition, Thomas More’s
foundational Utopia (1516), Francis Bacon’s New Atlantis (1626) and Jonathan Swift’s Gulliver’s
Travels (1726). It argues that early modern utopian literature offers two competing approaches to
the imagining of an ideal society: the practical-oriented approach initiated by Bacon, and the
moderate, sceptical approach inspired by Plato’s Republic and Ciceronian civil philosophy, which
is here represented by More and Swift. Modern utopias are widely understood as blueprints for
social reform by scholars such as Karl Popper (1945), Krishan Kumar (1987) and Ruth Levitas
(2009). This thesis argues, instead that this modern concept of utopia emerges when utopias adopt
the Baconian approach and break away from the classical heritage. More broadly, this thesis aims
to recover the value of the rich intellectual tradition of early modern utopian thinking; this
includes its sceptical engagement with the project of utopianism. We can only understand our
own desire for civic reform with a fuller understanding of this tradition.
In Chapter One, I argue that More’s Utopia is a cautionary tale against the passion for the
ideal society. The description of utopia is preceded by a dialogue on whether philosophers should
adapt to political reality or uphold their idea of justice without compromise. The dialogical form,
with its openness, encourages critical assessment of the zealous character Hythlodeaus who longs
for Utopia, and his position is further undermined when his monologue on the best
commonwealth becomes fraught with difficulties and contradictions. Chapter Two argues that
Bacon turns utopian literature into an applicable blueprint for political reform and his New
Atlantis thus marks a turning point for utopian literature. Concerned about the religious conflict
in his day, Bacon advocates a religiously tolerant and charitable utopia. For the first time, utopia
is conceived as a solution to a specific problem instead of the best commonwealth. In Chapter
Three, I argue that Gulliver’s Travels criticizes the Baconian approach for abandoning the topic of
the best commonwealth while simultaneously reappraising the Platonic ideal. Despite his
apparent endorsement of the classical tradition, Swift is in fact deeply sceptical of whether the
return to a Platonic approach is feasible when the understanding of man and society has been
radically reshaped by modern science
The Limits of State Sovereignty: An Exploration of Sardinian Minority Nationalism
Get PDFPhD ThesisThe concept of sovereignty has been at the heart of discussions in the discipline of International
Relations (IR) over the past 30 years, giving way to much-needed interrogations of the
exclusionary implications of realist treatments of the term as bound to the territoriality and
rationality of unified states. Overlooked in this critical literature, however, have been minority
nationalist articulations of sovereignty that do not conform to the neat categorizations of
inter/intra-state politics characteristic of realist imaginations of sovereign power. Responding
to this lacuna in IR scholarship, this thesis examines the role and significance of sovereignty in
Sardinian minority nationalist discourse. Through an analysis of ethnographic fieldnotes and
37 semi-structured interviews with ‘independentists’ conducted in Sardinia between 2017 and
2018, the research draws attention to how the term’s definition constitutes a complex site of
political contestation for minority nationalists. Drawing from a Gramscian perspective that
emphasises the importance of adopting a relational approach to the study of political discourses
as dialectically constructed, the research investigates how activists treated sovereignty as a way
of doing politics. Activists used the term in varying ways to contest conditions of economic
exploitation and political and cultural marginalization shaped by the unevenness of Italian
governance and capitalist development as well as to formulate alternative ‘myths’ of political
belonging and credibility. Arguing for an approach that considers sovereignty as shaped by the
ongoing effects of political dynamics of ‘revolution/restoration’, the research contributes to
ongoing efforts to produce non-essentializing depictions of people’s engagement with
sovereignty whilst not losing sight of the structuring effects of social relations of production on
perceptions of collective belonging, political legitimacy and the very possibilities of political
manoeuvre
Imaging horseradish peroxidase under electrochemical conditions
Get PDFPh. D. Thesis.In this work, potential dependent electrochemical characterisation has been performed
on horseradish peroxidase (HRP) molecules immobilised on annealed highly oriented
pyrolytic graphite (HOPG) surface immersed in phosphate buffer solution (PBS).
Electrochemical impedance spectroscopy (EIS) was applied to investigate the HRP
molecular capacitance. The observed HRP capacitance shows significant potential
dependency, which is analogous to that of a typical metal oxide semiconductor (MOS)
capacitor fabricated with p-type semiconductor materials. Accumulation region and
depletion region has been observed from the capacitance (C)-potential (U) curve of
the HRP molecules, and the “flat band potential”, at which there is no potential drop
within the semiconductor layer, has been determined as the potential where dC/dU-U
curve peaks. An MOS capacitor approximation is proposed to describe the potential
dependent capacitance behaviour of HRP molecules.
Scanning electrochemical potential microscopy (SECPM) and electrochemical
scanning tunnelling microscopy (EC-STM) has been applied to monitor the potential
drop in HRP molecules at single molecular level. SECPM maps the potential
distribution within the electrochemical double layer (EDL) and can resolve HRP
molecules with Angstrom resolution. Potential drop within HRP molecules is reflected
as potential dependent morphological variation in SECPM images. The observed HRP
apparent size peaks at the flat band potential. Similar potential dependency of HRP
apparent size is observed using EC-STM, as the potential drop being an influence on
the bias voltage between tip and substrate.
SECPM was also used to directly measure the EDL profile with alternating electrode
potential and electrolyte concentration. An exponential potential decay with reference
to the tip-substrate separation has been observed as predicted by Gouy-ChapmanStern model. Delayed response of potential decay, with significant dependence on the
local electrical field and ionic strength, was also observed at close tip-substrate
distance. A quantitative approach based on a novel mechanism which suggests high
resolution SECPM imaging could be attributed to direct electron exchange between tip
and substrate is proposed to interpret the delayed response of potential decay
Complex models for genetic sequence data
Get PDFPhD ThesisIn this thesis, the aim is to develop biologically motivated Bayesian models in two areas:
molecular phylogenetics and time-series metagenomics. In molecular phylogenetics, the
goal is generally to learn about the evolutionary history of a collection of species using
molecular sequence data, for example, DNA. Evolutionary history is represented graphically using evolutionary trees, where the root of a tree represents the most recent common
ancestor of all species in the tree. Substitutions in sequences are modelled through a continuous time Markov process, characterised by an instantaneous rate matrix, which standard models assume is stationary and time-reversible. These assumptions are biologically
questionable and induce a likelihood function which is invariant to a tree’s root position.
This is detrimental to inference, since a tree’s biological interpretation depends on where it
is rooted. By relaxing both assumptions, we introduce two new models whose likelihoods
can distinguish between rooted trees. These models are non-stationary, with step changes
in the rate matrix on each branch. Each rate matrix belongs to a non-reversible family
of Lie Markov models, which are closed under matrix multiplication. The two models
differ in that a different non-reversible Lie Markov model is used in each. We perform our
analysis in the Bayesian framework using Markov chain Monte Carlo methods. We assess
the performance of our models using a simulation study, before considering an application
to a Drosophila data set, where most models fail to identify a plausible root position.
In time-series metagenomics, counts of operational taxonomic units (OTUs), which
are pragmatic proxies for microbial species, are modelled over time. We have weekly
counts of different OTUs from two tanks in a wastewater treatment plant. We develop
a Bayesian hierarchical vector autoregressive model to model the dynamics of the OTUs,
whilst also incorporating environmental and chemical data. Clustering methods are explored to reduce the dimensionality of our data and mitigate the issue of large proportions
of zero-counts in the data. We use a seasonal phase-based clustering approach and a
symmetric, circulant, tri-diagonal error structure. The autoregressive coefficient matrix is
assumed to be sparse, so we explore different priors that allow for sparsity by analysing
simulated data sets before selecting the regularised horseshoe prior for our hierarchical
model. The chemical and environmental covariates are incorporated through a time varying mean. Finally, we fit the model to the data from each tank using Hamiltonian Monte
Carlo
An exploration of the experiences of children and young people (CYP)considered to have additional educational needs (AEN) in taking part indecision making processes in an English educational context
Get PDFD. App. Ed. Psy. ThesisThis thesis explores the experiences of children and young people (CYP) with
additional educational needs (AEN) of taking part in decision-making processes
(DMP) within the context of the English education system. It contains four chapters:
a systematic literature review, a critical consideration of research methodology and
ethics, an empirical research project and a reflexive chapter, which considers the
personal and professional implications of the thesis.
Chapter 1: The systematic literature review explores the experiences of CYP with
AEN in participating in decision making processes in light of the legislation changes
bought into place in 2014, which underpin CYP’s right to be active participants in
such processes. Thematic synthesis was used to analyse six papers, following a
detailed process of searching and selecting. Key Themes were identified as: How
CYP are viewed by adults around them; The decision-making process; CYP’s views;
and Relationships and Context. A theoretical framework was developed which
explored how these themes relate to one another. The review highlights the
importance of how both participation and CYP are conceptualised by adults around
them within the context of DMP and how this influences the DMP and the CYP’s
agency within that process. This is further shaped and underpinned by the
relationships around the CYP and how these support their participation in the DMP
and by the CYP’s own views and experiences.
Chapter 2: Chapter 2 provides a critical consideration of research methodology in
relation to my empirical research project on the experiences of girls with Autism
Spectrum Disorder (ASD) in taking part in decision making processes (DMP). In this
chapter I layout my own epistemological stance, I relate the findings from my SLR to
my methodological approach and explore the practical and ethical complexities which
underpin the approach to and design of my study.
Chapter 3: ‘It's my health care plan I should know what's going on.’ The purpose of
this empirical report is to develop an understanding of the lived experiences of girls
with ASD in contributing to their educational provision as part of the planning process
for their Education Health and Care Plans (EHCPs) and Annual Reviews (ARs). The
project was undertaken in the North East of England and adopted a qualitative
approach. Semi-structured interviews were carried out to explore the experience of
autistic girls of being part of EHCP and AR processes. The interviews were analysed
4
using Interpretative Phenomenological Analysis (IPA). The participants’ experiences
are discussed in the light of the wider literature and the implications this has for future
practice. Through developing an understanding of the girls’ experiences, I hope that
this will inform practice for professionals in supporting girls with autism in being part
of DMP and developing guidelines which enhance the quality of the EHCP plans to
reflect young people’s thoughts and wishes.
Chapter 4: This chapter provides a reflective and reflexive account of the research
process and outcomes and what this means for me as a trainee practitioner and
researcher. I consider the implications for future practice both personally and more
generally and how these may come abou
Corporate rebranding : an internal perspective (multiple case study into employee buy-in the higher education sector)
Get PDFPhD ThesisCorporate rebranding involves the modification or change of the logo, tagline and the corporate
brand name and is a common phenomenon in various industries such as telecom and an
emerging strategic trend in the higher education (HE) sector. Corporate rebranding strategy
often enables an organisation to become more relevant to its target market and improve its
positioning (Melewar et al., 2012; Sonenshein, 2010; Vallaster and Lindgreen, 2011; Miller
et.al, 2014). Employees play a vital role in, representing the brand values and fulfilling the
brand promise to an organisation’s customers (Balmer and Gray, 2003; Balmer 1995; Harris
and De Chernatony, 2006). The purpose of this study is to examine how the corporate
rebranding strategy is implemented internally and report on how buy-in from employees is
achieved.
Corporate rebranding studies in extant literature are sparse in the HE sector. To fill this gap, a
multiple case study of four UK universities was conducted to explore the complexity of the
phenomenon in the HE sector. Semi-structured in-depth interviews were conducted to establish
the relevance of major themes uncovered by an extensive literature review. This was followed
by thematic analysis of the data. Findings of the study emphasized upon the role of internal
brand communication in facilitating employees to accept the new corporate brand and their
buy-in. The involvement of employees and the role of leadership in the corporate rebranding
process were significant in gaining employee support. Employees who identified with the new
corporate brand and who were engaged and committed to their roles expressed a greater degree
of buy-in post rebranding. This is an important contribution to the literature on corporate
rebranding from an internal perspective. Further research is recommended to measure existing
levels of employee engagement and employee identification
Essays in option market liquidity
Get PDFPh. D. Thesis.This study investigates equity option market liquidity with different aspects of the bid-ask
spread, open interest, and trading volume in the US. We find a newly discovered determinant of
option liquidity: excess cash (that is, the level of cash reserve in excess of what can be captured
by firm characteristics) after accounting for underlying stock liquidity. We display evidence that
an increase of 1% in excess cash holding leads to a 0.58% reduction in option bid-ask spread,
0.28% increase in open interest, and 0.26% increase in trading volume. We also demonstrate that
there is a significantly positive linkage between stock and equity option market liquidity. The
results show that funding liquidity is a liquidity supplier of their market liquidity linkages. Stocks
with a higher probability of informed trading or facing greater short-selling pressures register a
significant reduction in the stock-equity option market liquidity interactions.
What is more, we analyse the effects of option market liquidity on stock price crash risk. We
find that the magnitude of crash risk will increase when the companies with a higher trading
volume and open interests of the options, while the option bid-ask spread will decrease market
crashes
Role of retrotransposons in hepatocellular carcinoma origin and progression – potential biomarker and therapeutic target?
Get PDFPhD ThesisIntroduction
Hepatocellular carcinoma (HCC) has the fourth highest cancer-related mortality worldwide and is
associated with a poor 5-year survival. Current therapies are limited and provide short median
survival. Thus, there is an urgent need to develop novel therapies. Long interspersed class elements1 (LINE1 or L1) activation has been demonstrated in several cancers including HCC and can inhibit
tumour suppressor genes or activate oncogenes. However, the role of L1 in hepatocarcinogenesis
is still unknown.
Methods
L1 expression was evaluated in the RNAseq data of HCC (n=372) from the cancer genome atlas
liver hepatocellular carcinoma (TCGA LIHC) study and formalin-fixed paraffin-embedded (FFPE)
patient biopsies (n=48) from our own biobank. RNAseq data was analysed for L1 counts and their
distribution was assessed in different HCC subclasses based on previously known molecular
classifications and associations with clinical parameters were explored. Likewise, FFPE samples
were stained for L1orf1p using an automated immunohistochemistry machine and were scored by
a pathologist; associations between L1orf1p expression in HCC and clinical parameters like
cirrhosis, tumour stage, albumin, bilirubin, alpha fetoprotein (AFP) and survival were explored.
The role of L1 was further characterised in different liver cancer cell lines utilising L1 knockdown
and overexpression systems. L1 knockdown was achieved using a lentivirus-based shRNA
expression vector targeting L1orf1 in Huh-7 cells. The influence of L1-knockdown on functional
properties such as proliferation, migration and invasion of the cells were investigated by comparing
L1-knockdown cells with wild type and non-targeted controls. RNAseq evaluated the influence of
L1-knockdown on whole transcriptome. Transient L1 full-length overexpression and conditional
L1orf1p overexpression were used to further validate the influence of L1 on cell signalling
pathways.
Results
L1 expression was elevated in HCC both at transcript and protein level compared to adjacent nontumour tissues. L1 transcripts correlated with high AFP, TP53 mutation, macrovascular invasion
and activated TGF-β signalling. Likewise, L1orf1p expression correlated with AFP, activated TGFβ signalling and poorly differentiated tumours. A positive association between L1orf1p and
pSMAD3 confirmed the relationship between L1 expression and TGF-β signalling in HCC. L1
knockdown in Huh-7 cells led to decrease in migratory and invasion capacity of the cells compared
to control cell lines. Furthermore, gene set enrichment analysis (GSEA) of the RNAseq data
demonstrated downregulation of TGF-β pathway in Huh7-L1knockdown cells compared to non-
targeting control cells, which was confirmed by Pai1-lucifease reporter assay. Conversely, L1
overexpression (full-length and L1orf1 alone) increased TGF-β signalling as confirmed by Pai1-
lucifease reporter assay, RT-qPCR and FACS analysis in HepG2, PLC/PRF-5 and HHL5 cell lines.
Conclusion
L1 is upregulated in human HCC and associated with high AFP, TP53 mutation and activated TGFβ signalling. Further in vitro studies demonstrated a crosstalk between L1orf1p and TGFβsignalling. Overall, our data demonstrates a causal link between L1orf1p and TGFβ signalling,
which presents a novel therapeutic avenue and potential treatment stratification biomarker for HCC