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Service level agreement specification for IoT application workflow activity deployment, configuration and monitoring
Get PDFPhD ThesisCurrently, we see the use of the Internet of Things (IoT) within various domains
such as healthcare, smart homes, smart cars, smart-x applications, and smart
cities. The number of applications based on IoT and cloud computing is projected
to increase rapidly over the next few years. IoT-based services must meet
the guaranteed levels of quality of service (QoS) to match users’ expectations.
Ensuring QoS through specifying the QoS constraints using service level agreements
(SLAs) is crucial. Also because of the potentially highly complex nature
of multi-layered IoT applications, lifecycle management (deployment, dynamic
reconfiguration, and monitoring) needs to be automated. To achieve this it is
essential to be able to specify SLAs in a machine-readable format.
currently available SLA specification languages are unable to accommodate
the unique characteristics (interdependency of its multi-layers) of the IoT domain.
Therefore, in this research, we propose a grammar for a syntactical structure
of an SLA specification for IoT. The grammar is based on a proposed conceptual
model that considers the main concepts that can be used to express the requirements
for most common hardware and software components of an IoT application
on an end-to-end basis. We follow the Goal Question Metric (GQM) approach to
evaluate the generality and expressiveness of the proposed grammar by reviewing
its concepts and their predefined lists of vocabularies against two use-cases
with a number of participants whose research interests are mainly related to IoT.
The results of the analysis show that the proposed grammar achieved 91.70% of
its generality goal and 93.43% of its expressiveness goal.
To enhance the process of specifying SLA terms, We then developed a toolkit
for creating SLA specifications for IoT applications. The toolkit is used to simplify
the process of capturing the requirements of IoT applications. We demonstrate
the effectiveness of the toolkit using a remote health monitoring service (RHMS)
use-case as well as applying a user experience measure to evaluate the tool by
applying a questionnaire-oriented approach. We discussed the applicability of our
tool by including it as a core component of two different applications: 1) a contextaware
recommender system for IoT configuration across layers; and 2) a tool for
automatically translating an SLA from JSON to a smart contract, deploying it
on different peer nodes that represent the contractual parties. The smart contract
is able to monitor the created SLA using Blockchain technology. These two
applications are utilized within our proposed SLA management framework for IoT.
Furthermore, we propose a greedy heuristic algorithm to decentralize workflow
activities of an IoT application across Edge and Cloud resources to enhance
response time, cost, energy consumption and network usage. We evaluated the
efficiency of our proposed approach using iFogSim simulator. The performance
analysis shows that the proposed algorithm minimized cost, execution time, networking,
and Cloud energy consumption compared to Cloud-only and edge-ward
placement approaches
A nested, prospective, longitudinal cohort study exploring the impact of delirium on cognitive outcomes
Get PDFPh. D. Thesis.Background: Delirium is a severe neuropsychiatric syndrome of brain dysfunction precipitated by acute illness and characterised by acute and fluctuating inattention and other cognitive and perceptual deficits. Delirium is common, distressing and associated with poor outcomes. Previous studies examining the impact of delirium on cognitive trajectories have been limited by incomplete ascertainment of baseline cognition or a lack of prospective delirium assessments.
The DECIDE study aimed to explore the association between delirium and cognitive function over time in participants in an existing population-based cohort aged 65 years and older with known baseline cognition.
Methods: Over a 12-month period, surviving participants from the Cognitive Function and Ageing Study II-Newcastle were screened for delirium on admission to hospital. Baseline characteristics along with disease relevant clinical parameters were recorded. The progression/resolution of delirium was monitored. In those with and without delirium, cognitive decline and dementia was assessed at one-year follow-up. The effect of delirium on cognitive function over time was evaluated, independent of baseline cognition and illness severity, along with the predictive value of clinical parameters.
Results: 82 of 205 participants developed delirium in hospital during the study period (40%). 18 of the 135 participants completing one-year follow-up interviews received a new diagnosis of dementia. Delirium was associated with an increased risk of new dementia diagnosis at follow up, independent of illness severity and baseline cognition (OR 8.76 [CI: 1.85 – 41.37], p=0.006). More than 5 days of delirium and more severe delirium were independently associated with worse cognitive outcomes.
Conclusions: An episode of delirium whilst in hospital significantly increases risk of future cognitive decline and dementia, independent of illness severity and baseline cognition. Given that delirium has been shown to be preventable in around a third of cases, it can be proposed that delirium is a potentially modifiable risk factor for dementia.Alzheimer’s Societ
‘Shrink-Wrapping’ nanoscale objects
Get PDFPhD ThesisThis thesis describes the ‘structural metamorphosis’ of discrete single-chain polymer
nanoparticles (SCPNs) – an architecture in which a linear polymer chain is intramolecularly
crosslinked – into intermolecularly crosslinked polymer films. It was hypothesized that this
process could be exploited for the ‘shrink-wrapping’ of 3D nanoscale objects, whereby SCPNs
concentrate themselves onto the surface of the object through complementary non-covalent
interactions and then spontaneously crosslink with their neighbouring polymer chains to afford
a covalently crosslinked film. With the ambitious goal of ‘shrink-wrapping’ virus-like particles
(VLPs) in mind, this thesis developed the concept by ‘wrapping’ nano- and microscale objects
of increasing complexity. Chapter 1 proposes a definition for ‘structural metamorphosis’ and
describes how this phenomenon could be exploited to drive ‘shrink-wrapping’ of virus-like
particles. Chapter 2 explores the ‘shrink-wrapping’ of simian virus 40 and Model System I,
where the ‘wrapping’ process is driven by simple electrostatic interactions. Chapter 3
describes Model System II, in which specific carbohydrate-receptor interactions drive the
‘shrink-wrapping’ of protein-functionalized silica micro- and nanoparticles. The success of
these investigations is largely owed to the development of a highly hydrophilic aldehyde
polymer scaffold that was constructed to circumnavigate issues of non-specific binding
between polymers and the particle surface. Chapter 4 reports progress in the ‘shrink-wrapping’
of SV40 viral capsid, describing work towards the synthesis of SCPNs functionalized with the
oligosaccharide GM1 – the native ligand of SV40. The ‘shrink-wrapping’ of sensitive
biomacromolecular targets such as VLPs requires hydrazone exchange chemistry to operate
on a reasonable timescale at physiological pH. Published work in Chapter 5 investigates rateenhancing
structural features which lead to rapid hydrazone exchange processes at neutral
pH. These findings are anticipated to have important consequences on the development of
structurally adaptive polymers, materials, molecular machines, nanoparticles and surfaces,
where hydrazone exchange chemistry is commonly exploited to endow these systems with
stimuli-responsive behaviour
Investigating the regulation of alternative splicing by Tra2 proteins and RBMX in triple negative breast cancer cells
Get PDFPhD ThesisAlternative splicing is a key process that enables the expression of a large number of proteins from a limited number of genes. Regulation of alternative splicing has been directly linked with the hallmarks of cancer. Human Transformer 2-α and -β are two homologous RNA binding proteins involved in the regulation of alternative splicing that are overexpressed in many different cancers. Previous work suggests Tra2β interacts closely with RBMX, encoded by the gene RBMX, to regulate the splicing of key pathologically related genes such as SMN2. The objective of this study is to investigate the role of alternative splicing regulators in breast cancer in order to further understand their biological function. Firstly, I utilise previously obtained RNAseq data from the double knockdown of Tra2α and Tra2β in the MDA-MB-231 breast cancer cell line to identify an extended number of genes regulated by Tra2 proteins using recently developed bioinformatics pipelines. The analysis revealed a range of alternative events including intron retentions, alternative 3’ and 5’ splice sites and exon repression events, suggesting different mechanisms of splice site regulation by Tra2 proteins. I experimentally validated the results of the RNAseq analysis by PCR. Subsequent Gene Ontology enrichment analysis of Tra2-regulated targets reveals several genes involved in the cellular response to DNA damage. I employed western immunoblotting to investigate the protein expression changes in these genes and was able to detect short protein isoforms expressed for MBD4 and XPA. Subsequently, nuclear fractionation and immunofluorescence microscopy of Tra2 depleted cells showed cytoplasmic localisation of the short isoforms for both MBD4 and XPA. In order to determine the role of the alternative isoforms regulated by Tra2 proteins, antisense oligonucleotide targeting exon 5 of BRIP1, exon 3 of CHEK1, and exon 5 of XPA were transfected into MDA-MB-231 cells. Expression of the short XPA isoform using antisense oligonucleotides results in an increase of γH2AX and reduced cell viability. This data suggests Tra2 proteins sustain the DNA integrity and protect the cells from death by ensuring the expression of correctly spliced DNA repair genes. In order to compare the role of Tra2 proteins with the commonly associated splicing regulator RBMX, I knocked down the expression of RBMX in MDA-MB-231 cells and obtained RNAseq data. Bioinformatics analysis was able to identify many commonly regulated alternative events, but also some novel isoforms regulated by RBMX alone. RNAseq data also unveiled an interesting autoregulatory mechanism for the RBMX gene, whereby the expression of RBMX is regulated by alternative splicing of the 3’ UTR. Subsequent examination of Upf1 knockdown cells showed stabilisation of the alternating isoform of RBMX indicating it is targeted by nonsense mediated decay. Future work into the role of RBMX regulated targets similar to the work done for Tra2-regulated genes could reveal a complete and clear picture of the function of RBMX in breast cancer cells
Nucleation, growth and dissolution of faceted single crystals
Get PDFEng. D. Thesis.The crystallisation and dissolution (non-sink) behaviour from the solution phase is studied for some selected pharmaceutical representative materials, notably urea and paracetamol, and is interrelated to an assessment of surface chemistry of the crystal habit facets.
The inclusion of a small amount of biuret, a known decomposition impurity of urea, is found to increase the solution metastable zone. Polythermal analysis is consistent with a concentration dependence of the nucleation behaviour of both the pure and the doped systems associated with the mechanism changing from progressive to instantaneous with increasing concentration, with a concomitant decrease in the interfacial tension and a significant increase in nucleation rate of the doped system, from 9.22-20.48 to 9.25-67.73 nm-3. s-1, and decrease in the critical nucleus size. The crystal habit of urea in solution is found to be dominated by the {110} and smaller polar {111} capping faces resulting in the {-1-1-1} not being observed. The mean crystal growth rates of the {110} and {111} faces are found to increase with respect to supersaturation with {111} exhibiting a greater level of increase than {110}. The addition of biuret to the solution is found to have a greater effect on retarding the growth of {111} compared to {110}, resulting in a more compact morphology. Rationalising this behaviour with computational molecular modelling studies reveals stronger additive binding on {111} compared to {110}.
The mean crystal dissolution rates of {110} and {111} faces of urea in ethanolic solutions are found to increase with respect to the degree of undersaturation, with the dissolution behaviour being mechanistically consistent with the growth behaviour. The mean crystal dissolution rates of both faces in acetonitrile are very similar to each other, and to the dissolution rate of the {110} face in ethanol. The dissolution rate of the {111} face in ethanol is found to be faster than that of the other faces. Rationalising this behaviour with computational molecular modelling reveals a higher wetting energy of {111} compared to {110}. Dissolution modelling based on the experimental data, were consistent with boundary layer thicknesses of 0.5μm and 0.3μm for the same undercoolings for ethanol and acetonitrile, respectively. These values are smaller than expected but are consistent with modelling data.
The relative solubilities of paracetamol are higher in acetonitrile than in fed state simulated intestinal fluid (FeSSIF). The crystal habit of paracetamol in solution is
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found to exhibit five equivalent morphologically significant faces, giving rise to a prismatic crystal. The mean crystal dissolution rates of these faces are found to increase with respect to degree of undersaturation in acetonitrile, with the dissolution rates of all faces being very similar. The mean crystal dissolution rate of these faces is found to increase with respect to temperature in FeSSIF, with the dissolution rates of the faces being similar. The dissolution rates in acetonitrile and FeSSIF are rationalised through prediction of the intermolecular interactions. Dissolution modelling revealed the boundary layer thicknesses to be 0.3μm and 0.1μm for acetonitrile and FeSSIF, respectively. This might reflect the greater number of binding sites of water compared to acetonitrile, as well as the assumption that water is a representative probe for FeSSIF.
The importance of this work in enhancing the quality of dissolution testing is also highlighted, notably, the utility of relating dissolution properties at the single particle level to the same material as it progresses throughout the drug product processing cycle
An all-digital charge to digital converter
Get PDFPhD ThesisDuring the last two decades, the topic of the Internet of Things
(IoT) has become very popular. It provides an idea that everything
in the real world should be connected with the internet
in the future. Integrating sensors into small wireless networked
nodes is a huge challenge due to the low power/energy budget
in wireless sensor systems. An integrated sensor normally
consumes significant power and has complex design which increases
the cost. The core part of the sensor is the sensor interface
which consumes major power especially for a capacitor-based
sensor.
Capacitive sensors and voltage sensors are two frequently
used sensor types in the wireless sensor family. Capacitive sensors,
that transform capacitance values into digital outputs, can
be used in areas such as biomedical, environmental, and mobile
applications. Voltage sensors are also widely used in many modern
areas such as Energy Harvesting (EH) systems. Both of these
sensors may make use of sensor interfaces to transform a measured
analogue signal into a frequency output or a digital code
for use in a digital system. Existing sensor interfaces normally
use complex analog-to-digital converter (ADC) techniques that
consume high power and suffers from slow sensing response.
This thesis proposes a smart all-digital dual-use capacitorbased
sensor interface called charge to digital converter (QDC).
This QDC is capable of not only sensing capacitance but also
sensing voltages by using fully digital solutions based on iterative
delay chain discharge. Unlike the conventional methods
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that only treats the sensed capacitance only as the input signal,
this thesis proposes a method that can directly use the stored
energy from the sensed capacitance as well to power parts of
the circuit, which simplifies the design and saves power. By
playing with the capacitance and input voltage, it can be used
as a capacitance-to-digital converter (CDC) to sense capacitance
under fixed input voltage and it also can be used as a capacitorbased
voltage sensor interface to measure voltage level under
fixed capacitance. The new method achieves the same accuracy
with less than half the circuit size, and 25% and 33% savings on
power and energy consumption compared with the state of art
benchmark. The method has been validated by experimenting
with a chip fabricated in 350nm process, in addition to extensive
simulation analysis
Models and simulation of blockchain systems
Get PDFPh. D. ThesisIn the literature, there are a variety of proposed blockchain systems (e.g.,
Bitcoin and Ethereum), each of which with its own design decisions. Both
in the design and the deployment of blockchain systems, many configuration choices and design decisions need to be made. Investigating different
implementation and design choices is neither feasible nor practical on real
blockchain systems. Simulation models emerge as an excellent technique
to study blockchains without either implementing a new system or interrupting an existing one. Despite some attempts in the literature to
utilise simulation models to evaluate specific aspects of blockchain systems, there is a lack of a general-purpose, flexible, extensible and widely
usable simulation tool for blockchains.
In this thesis, we contribute to the field of blockchain analysis by proposing
BlockSim as a generic framework to build discrete-event dynamic system
models for blockchain systems. BlockSim aims to provide flexible and
extensible simulation constructs to study a variety of blockchains and a
set of design and deployment questions. BlockSim is implemented as a
publicly available simulation tool and thoroughly validated against reallife systems and measurement studies.
Another contribution of this thesis is an extensive analysis to estimate
the distributions for Ethereum smart contract using data for over 300,000
real transactions. To run realistic simulation studies, we integrate these
distributions into the simulator to generate representative transactions.
Furthermore, this thesis offers two extensive data-driven simulation studies related to Ethereum smart contracts that demonstrate the applicability
and usefulness of BlockSim. The first study is the analysis of the Ethereum
Verifier’s Dilemma and the proposal of two approaches (parallelisation and
active insertion of invalid blocks) to mitigate its implications. The second
study is the analysis of the uncertainty that miners face about the fee and
cost of transactions and its impact on the received profits.Ministry
of Education and Taibah Universit
Bioengineering: Stratifying the Immune Response to Biomaterials
Get PDFPhD ThesisEarly failure of Metal-on-Metal (MoM) joint implants is often due to adverse reaction to
metal debris (ARMD). These MoM implants are composed of a cobalt-chromium
(CoCr) alloy which generates nanoscale particles and metal ions. Cobalt ions can
activate the innate immune receptor, Toll-like receptor 4 (TLR4), increasing secretion
of inflammatory cytokines/chemokines.
For this study, CoCr particles were generated in a multi-directional pin-on-plate wear
simulator and characterised for use in cell treatments. In human THP-1 macrophages,
CoCr particles were found to increase secretion of pro-inflammatory chemokines and
cytokines including IL-8, CCL2, CCL3, CCL4 and IL-1 The gene expression of IL-8
and CCL3 was also up-regulated in response to CoCr particles. The expression of
these markers was found to be largely TLR4-dependent as a small molecule TLR4
antagonist, CLI-095, significantly reduced these observed effects.
Further investigation demonstrated that CoCr particles can also increase expression
of the adhesion molecules ICAM-1 and VCAM-1 in the human endothelial cell line,
HMEC-1. Furthermore, CoCr particle stimulation in HMEC-1 cells led to increased
neutrophil migration in a chemotaxis assay. In periprosthetic tissue retrieved from
patients undergoing hip and knee revision surgery, there was evidence of immune cell
infiltration and the presence of macrophages and T cells.
THP-1 macrophages were also treated with aluminium and zirconium oxides which are
commonly used in ceramic hip implants. Both treatments resulted in significant TLR4-
dependent increases to IL-8, CCL2, CCL3 and CCL4 gene expression and protein
secretion. Use of ATP to mimic ‘danger’ signalling following initial priming with ceramics
caused significant increases to IL-1 expression.
These data demonstrate that CoCr particles and ceramic oxides can induce an
immune response by up-regulating the expression of pro-inflammatory chemokines by
a mechanism that appears to be largely TLR4-dependent. This study demonstrates a
potential role for innate immunological mechanisms in the development of ARMD in
patients with failed prosthetic joint implants
A spatiotemporal natural hazard risk assessment framework for Thailand
Get PDFPhD ThesisRoyal Thai Government and Geo-Informatics and Space Teachnology Development Agency(GISTDA) under Thailand's Ministry of Higher Education, Science, Research and Innovation
Improving Efficiency of the Court Service in Pakistan : A Comparative Study of the Options for Reform
Get PDFPh. D. Thesis.The project is directed to formulate recommendations to improve the efficiency of court service in Pakistan as to civil litigation at the district level. The New Civil Procedure Framework (NCPF) is presented as a reform model for Pakistan with a renewed theoretical construct, innovative strategies and specific practical measures. The study focuses on the efficiency perspective of court service, its appraisal and improvement through procedural and managerial tools. Efficiency is measured through quantifiable indicators using empirical data which shows delay and abuse of court process as alarming performance issues causing tremendous sufferings for the end-users in Pakistani district courts. This analysis offers clues to identify the problem areas, i.e. outdated procedural law and its underlying theoretical assumptions and case management deficit. The NCPF, being a unique reform model, at first identifies the theoretical fault lines of the existing system and its inadequacy to contain performance issues in the long run. The broad framework of Woolf’s experiment and Singapore’s judicial modernization are taken into account while designing the NCPF, but the effort remained far from a blind replication. The magnitude and intensity of delay and abuse of court process in Pakistan necessitated looking beyond Woolf and Singapore. Though the theoretical foundation of NCPF model draws on Woolf’s theory of balancing key imperatives (i.e. accuracy, expedition and economy) and the principle of proportionality, yet the innovative neo-proceduralist approach is its distinguishing feature. It is argued that the law must dictate the pace of litigation while the judge is only to execute the compliance regime with no or little discretion to condone. Following these constructs, the NCPF requires rigours initial scrutiny of cases, forewarning as to penal consequences of frivolous litigation and non-compliance, pre-planning, and use of modern management and digital tools to ensure expedition and efficiency of judicial service in Pakistan