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Investigation into the effects of infrared,visible and ultraviolet wavelengths of the solar spectrum on human skin cell damage
Get PDFPhD ThesisUltraviolet light is known to cause skin damage and photoaging, and chronic exposure can
lead to skin cancer. The effects of visible light and infrared light on the skin are less well
understood, though some believe they contribute to oxidative stress and photoaging.
Understanding the mechanisms of photodamage is important for the development of
sunscreens to effectively prevent photodamage and maintain skin health. The objective of
this study was to optimise experimental conditions for assaying the irradiation of visible and
infrared light on human skin cells in vitro, and determining the effects of these wavelengths
on reactive oxygen species (ROS) production and gene expression.
Temperature control during infrared irradiations is critical to understanding the effect of
light on chromophores rather than through heating. Without adequate temperature control,
tissue culture plates could exceed 60°C, resulting in greater than 90% cell death. Careful
consideration of medium conditions is crucial for ensuring results are not due to unexpected
interactions of light with medium components. The presence of riboflavin, a component of
almost all commercially available cell culture medium, reduced viability in cells irradiated
with blue light by 45%.
When adequately controlled, it was found that 2 hours of infrared at solar intensity or a 10-
hour equivalent dose at 9 x peak solar intensity did not affect ROS as measured with flow
cytometry, and RNA sequencing showed few changes to gene expression with less than 10
differentially expressed genes. A dose of visible light equivalent to one hour of peak solar
visible light did not induce a ROS signal measurable after irradiation. However, it was found
to affect extracellular matrix genes MMP1 and MMP3 to similar extents to a 2.16 standard
erythemal dose of UV and induce ferritin expression where the UV dose did not, indicating a
possible effect on photoaging and oxidative stress.
In summary, this thesis demonstrates that infrared light has little effect through absorption
of chromophores, but visible light may affect fibroblast extracellular matrix regulation and
iron homeostasis.Biotechnology and Biological Sciences Research
Council (BBSRC) and CROD
Utilization of biochar produced from agricultural residues for the removal of pesticide and pharmaceutical micropollutants in surface water biofiltration
Get PDFPhD ThesisIn recent years, there has been a growing interest in exploring possible agro-based biochar
for use in different remediation applications. This thesis therefore investigated the
feasibility for biochar produced from rice straw (RSBC), corn cob (CCBC), coconut husk
(CHBC) and coconut shell (CHBC) to immobilize micropollutants in water, with the aim
of finding a better alternative to activated carbon (GAC). First, 3% (w/w) amendment
applications of the selected adsorbents were set up to evaluate their influence on leachate
properties. Results showed significant increase in pH (>8) in biochar leachates which
decreased leachability of metals, while GAC with lower pH (<6) showed greater metal
leaching. Also, all amendments increased hydraulic conductivity (K) by 11.6%, except for
CHBC and CCBC that decreased K by 54.7% and 36.9%, respectively. The characteristics
of the biochars in batch adsorption studies were compared to evaluate their adsorption of
four pharmaceuticals and two herbicides micropollutants. Although, removal efficiencies
were feedstock type dependent, RSBC exhibited significantly higher sorption capacity of
12.81±0.13 mg/g (at 0.5 g/L and 10 days contact time) for oxytetracycline (OTC),
compared to that of GAC of 19.11±0.72 mg/g for the same compound. Partition coefficient
(Kd) values were used to compare how effective the different adsorbents are in the
reduction of micropollutants availability and transfer in aqueous solution. Comparatively,
the kinetic study indicated that RSBC and CHBC showed better adsorption for most
micropollutants than other biochars. CHBC amendment of sand biofilters showed a
reduction in hydraulic flow from 24.48 m/day in fresh fine sand (FISA) to 1.87 m/day in
CHBC amended fine sand, which facilitated the micropollutant biodegradation process.
All measured compounds were attenuated by a combination of sorption and biodegradation
processes, however, pharmaceuticals were removed more significantly (p<0.05) than
herbicides in both amendment types. Overall, biodegradation accounted for >90% removal
in CHBC and <60% for FISA columns. Microbial analysis confirmed a shift in bacterial
community composition for CHBC versus FISA columns, but depth as the most critical
community structuring factor. In this work, RSBC and CHBC were shown to have
potential for cheap, and environmentally friendly amendments to enhance removal of
micropollutants in surface water biofiltration
The Effects of Instrument Lubricants on the Physical and Mechanical Properties of Resin-Based Composites
Get PDFPh. D. ThesisUncured resin-based composites (RBCs) tend to stick to the placement instrument
instead of cavity walls, potentially increasing void formation and margin discrepancy.
Instrument lubricants (ILs) are used to overcome this problem, but they may affect the
properties of RBC restorations. One hundred registered UK dentists were surveyed
using a bespoke questionnaire to investigate their perspective on IL use and
understand why and how they used them. Additionally, different laboratory
investigations were conducted, based on the survey data, to test the effects of ILs on
the physical and mechanical properties of RBCs. Two RBCs were treated with three
classes of ILs —solvents, bonding agents and wetting resins —to investigate the
effects different ILs have on the physical and mechanical properties of RBCs. Several
areas were tested: degree of conversion, water uptake, Martens hardness, diametral
tensile strength, microtensile bonding strength (μTBS), and the appearance of
changes at the increment interface. The survey revealed that about 50% of the dentists
used lubricants (32% response rate), of which bonding agents (67%) and wetting
resins (33%) were most common. These were applied with microbrushes (47%) and
by wiping the placement instruments (40%). The solvents, bonding agents and wetting
resins created significant reductions in diametral tensile strength and Martens
hardness, and increased water uptake compared to control groups fabricated without
lubricants. The μTBS significantly reduced following treatment with solvents and
bonding agents, but there was no reduction from the wetting resins. The respondents
used lubricants to aid manipulation during placement. However, these materials have
an impact upon physical and mechanical properties with solvents and bonding agents
having the greater effect. Therefore, the use of ILs to manipulate the RBC should be
limited or avoided.King Khalid Universit
Control of Diffuse Agricultural Pollution and Management of Trans-boundary Waterways : A comparative analysis of the policy making process in Ireland and Northern Ireland
Get PDFPh. D. ThesisRegulating diffuse agricultural pollution in the island of Ireland’s trans-border waterway catchments is a ‘wicked problem’. Alongside the need to mitigate agriculture-related water pollution are parallel and competing needs to support a socially and economically important agri-food industry and deliver public ‘goods’ under a paradigm of multifunctionality. Meeting all these objectives simultaneously is not possible. Thus, finding balance between various competing policy objectives is an important policy goal. Beyond this, co-managing trans-boundary waterways is a significant challenge for policymakers, not least because ecosystem boundaries typically do not align with administrative ones. The United Kingdom’s exit from the European Union is set to exacerbate this challenge by vastly increasing administrative complexity on the island.
This research contributes to academic literature on wicked policy problems by helping to improve understanding of the complex social factors that underpin and influence the agri-environmental policymaking process on the island of Ireland, particularly as it relates to the wicked problem of diffuse agricultural water pollution in trans-border catchments. Employing qualitative methods (interviews, focus groups) within a case study methodology, it draws on theories of agricultural post-exceptionalism, policy network analysis and leverage points to describe governance structures and their influence on agri-environmental policymaking. It also presents a modified power framework based on Lukes’ (1974) ‘three faces’ model that describes how actors within the agri-food sector obtain and employ power within the agri-environmental policymaking arena. This thesis argues that the structure of, and power distributions within, agri-environmental policymaking networks on the island of Ireland have significant implications for policy outcomes. It also demonstrates how actors within these networks capitalise on gaps left by multiple competing policy channels and complex administrative environments to advance their interests.
It finds that in Ireland and Northern Ireland, the agri-food sector continues to be treated as exceptional, and agri-food actors remain central within policymaking networks as a result. This means that agri-environmental policy continues to favour agri-food interests, often to the detriment of the island’s waterways. It also finds that power distributions within the agri-food sector impact water quality. Some agri-food sectors (e.g., dairy, poultry) hold more power than others meaning they can resist important regulation such as water pollution initiatives, rendering such regulation ineffective. Meanwhile, other sectors (e.g., beef and sheep) are left out of the conversation, which compromises potential policy solutions. It argues that for future policies to adequately address the challenge of agriculture‐related water pollution, agri-food system governance must become more equitable and nuanced, allowing for tangible consideration of the challenges that different agriculture sectors face. It also argues that if diffuse agricultural pollution is to be fundamentally addressed, change is required in both the institutional structures that support the current policymaking apparatus, and in the productivist, export-focused logic currently underpinning the Irish agri-food industry.Teagasc Walsh Scholar Programme, Newcastle University, Enviresearch Foundatio
Characterisation of anucleate cells
Get PDFPhD ThesisBacteria are beneficial in industry as they are easily genetically manipulated to express
proteins, enzymes or full pathways while remaining cheap to grow in large batches with simple
feed stocks. However, there are limitations associated with this as overproduction can lead to
interference from complex cellular processes or metabolic burden. Metabolic burden is caused
when essential cellular resources, such as energy and carbon, are diverted to the engineered
pathway used for bio-production. To overcome limitations, this project aims to
compartmentalise biosynthetic pathways into anucleate compartments of Bacillus subtilis,
Escherichia coli and Synechococcus elongatus while regulating expression in nucleated cells.
Division mutants were constructed in each chassis for the production of minicells or maxicells.
Analysis of these anucleate producing strains was done to determine the properties of plasmid
replicons with respect to gene expression and segregation into anucleate cells. Here the
Plac/LacI regulation system was used so expression in nucleated rod cells was repressed while
expression occurred within anucleate compartments. Good repression was present in the
minicell and maxicell producing strains of B. subtilis, however, only 50% of anucleate cells
were expressing GFP. There were efforts in B. subtilis to alter copy number to understand the
pLS20 replicon and increase the amount of anucleate cells gaining a plasmid, however, there
was no single mutant which worked best in minicells. There was a dramatic increase in maxicell
expression with copy number mutants but there was still a cost to the regulation system in
nucleated cells. In E. coli, the systems regulation does not repress as efficiently in nucleated
mother cells compared to B. subtilis. Studies from this work revealed that the RSF1010 driven
plasmids were better for minicell expression where ~30-35% minicells were GFP positive.
Although a minicell producing mutant was constructed for S. elongatus, integration of a
plasmid and repression system remained problematic. However, the minicell producing
phenotype was characterised in greater detail using widefield fluorescence and transmission
electron microscopy. This work contributes to the wider Portabolomics project aiming to bridge
the gap between academia and industry
Designing with and for social innovation: service design by working with youth civic groups in Lebanon
Get PDFPh. D. ThesisWithin contested contexts marked by profound political, social, and economic changes, social
innovation emerges to reconceptualise services, ideas, and products. At the intersection of
multifaceted agendas, social innovation brings forward a paradigm shift in tackling problems that
traditional methods fail to adequately address. In this thesis, I focus on the context of Lebanon
which suffers from political, economic, public health, and social turmoil. In light of a fragmented,
politicised and weak welfare system, Lebanon is a fertile ground for the proliferation of nongovernmental
organisations (NGOs) and particularly youth-led, grassroots organisations that
challenge the existing status quo by devising novel ways of creating and delivering services.
Therefore, how can we surface, structure, and scale youth-driven social innovation in service
design and delivery, through participatory methods within contested spaces? With participatory
action research (PAR) as an overarching methodology and by applying embedded ethnography,
participatory design (PD), and service design methods, this thesis examines social innovation
focussed on designing services across three distinct contexts of civic engagement. These include:
1) large-scale organisations in which the youth are positioned as beneficiaries; 2) small-scale
youth-led organisations; and 3) the Lebanese social movement of 2019, encompassing a
constellation of local and transnational grassroots. Findings reveal tensions when attempting to
adopt participatory research methods within environments which lack inherent participatory
attributes. Conditions needed for the creation of technology-supported social innovation for
service delivery within such a complex context surface, and new forms of socio-technical
infrastructures resulting from circumstances of emergency and uncertainty are highlighted. I
contend that a hybrid model of design with top down and bottom-up elements is most suited to
be able to structure and scale out social innovation especially while navigating both embedded
and emerging issues of participation and power. Also, the design and adoption of digital
technology within such contexts requires re-purposing familiar tools and building new social
practices around them. Finally, due to the ongoing and evolving negotiations that need to take
place as a result of circumstances on the ground, researchers ought to shift roles ranging from
facilitators to activists when working within such contested spaces
Computational Approaches to Generating Diverse Enzyme Panels
Get PDFPh. D. ThesisMotivation
Enzymes are complex macromolecules crucial to life on earth. From bacteria to human
beings, all organisms use enzymes to catalyse the many thousands of chemical reactions
occurring in their cells. Enzyme functions are so diverse that the use of enzymes in
industries like pharmaceuticals and agriculture has gained popularity over recent years
as ”biocatalysts”.
Unfortunately, the confident laboratory-based characterisation of enzyme function has
lagged behind a massive increase in sequencing data, slowing down initiatives that
look to use biocatalysts as part of their chemical processes. Computational methods
for identifying biocatalysts do exist, but often falter due to the complexity of enzymes
and sequence bias, leaving much of the catalytic space of enzymes and their families
undiscovered.
This thesis has two major themes: the development of in silico approaches for curating
diverse panels of novel enzyme sequences for experimental characterisation, and of
tooling that integrates in silico panel creation and in vitro enzyme characterisation
into a unified and iterative framework.
Contributions of this thesis
The contributions of this thesis can be divided into the two larger themes, starting
with the diverse panel selection of sequences from an enzyme family:
• A novel type of protein network based on patterns of coevolving residues that
can be used to identify functionally-interesting groupings in enzyme families.
• The automatic sampling of functionally diverse subsets of enzyme sequences by
solving the maximum diversity problem.
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• A study into the viability of artificially increasing enzyme family diversity through
neural networks-based generation of synthetic sequences.
The second theme, which deals with built tools for bridging the gap between the in
silico and in vitro side of enzyme family exploration:
• A platform that integrates the panel selection process and resulting characterisation data to promote an iterative approach to exploring enzyme families.
• A repository for storing the metadata generated by the major steps of characterisation assays in the lab.EPSRC and Prozomix Limite
The Politics of Paradise: Aesthetic Fantasies of Otherwise within Tourist Economies in Northeast Brazil
Get PDFPhD ThesisThis thesis asks how the concept of paradise offers an insight into the formation of political communities
in tourist locations. I argue that ideas of paradise underpin the fantasies through which residents of Praia
da Pipa, a paradisial beach town in northeast Brazil, cope with the changing demands of touristic
economies as the town grows. Through their embodied engagements with paradisial space, I argue
residents produce, reproduce, and challenge inequalities inherent to the developing tourist industry and
persisting colonial social hierarchy through the political communities they form. Using ethnographic
data, I explore the multiple and contrasting ways in which residents make sense of the world around
them through the sense that life in Pipa should somehow be different and the way their engagements
with the town both impart this expectation and challenge it, creating paradise as they do. To do this, I
trace four interconnected modes of paradise as residents sense and enact it in the town to demonstrate
the often-surprising ways in which its fantasies form the basis for possible social relations there. Firstly,
I look at the way spatial conflicts engender governance through rendering the space one of consumption;
secondly I explore the temporal framings through which residents craft their worlds through
attachments to paradise; thirdly I consider how Edenic understandings underpin resistance; and finally
I explore how the circulation of touristic capital in the form of mobility prompts chance connections
and solidarities. Fantasies of paradise enable unexpected communities of sense within expected
hierarchies of colonial power and capital, through which residents enact a critique of the limits of
utopian promises of touristic development and its economies of dispossession. Overall, this
interdisciplinary thesis contributes to understandings of the role of fantasies in the production of and
challenges to touristic development and the political relations therein
The cytoskeleton and polarity in the C. elegans embryo: Understanding microtubule dependent signalling in the generation of cellular asymmetries.
Get PDFPh. D. ThesisAsymmetry within cells relies on the uneven distribution of molecules and organelles required for cell function and viability. For example, epithelial cells form an apical-basolateral polarity which confers different protein and phospholipid compositions at the membrane of each domain. Controlled enrichment of integrins on the basolateral domain ensures that an epithelial cell remains anchored to the basement membrane, required to prevent cell plasticity and epithelial to mesenchymal transition. Migrating cells require the assembly of the cytoskeleton at their leading edge and disassembly at the rear to move with direction, whilst asymmetrically dividing cells rely on different concentrations of proteins and RNAs across the mitotic axis to program the distinct fates of each daughter cell after division. The polarity effector proteins, which control polarity establishment and maintenance in cells are broadly conserved, however respond to different cues and have variable contributions dependent on cell type, organism, and stage, be it inherited or de novo polarity. Failure to generate and maintain correct asymmetry in cells can lead to disease states including cancer.
In our lab, we study the contribution of the cytoskeleton in the establishment of cell polarity. For this, we use the C. elegans zygote as a model due to the conserved molecular machinery and its well characterised embryonic development. Asymmetry first initiates in the single cell zygote, post-fertilisation, upon which the globally dynamic actomyosin network underlying the cell membrane undergoes localised relaxation at the site in closest proximity to the matured sperm-derived centrosome pair. The resultant gradient of actomyosin contraction generates a cortical cytoplasmic flow towards the future anterior pole and carries with it, the cortical anterior polarity effector PAR proteins. The newly unoccupied cortex is then inhabited by a cytoplasmic pool of posterior PAR proteins. The cue for this change in cortical dynamics is derived from a signal of sequestered AIR-1 which diffuses from the sperm donated centrosome. A second, lesser studied, pathway to establish polarity in the zygote is believed to occur due to the enhanced stabilisation of posterior PARs at the cortex, aided via centrosomal microtubules which prevent phosphorylation from anterior PARs that initially inhibit posterior PAR membrane recruitment. Through mutual antagonism the anterior and posterior PARs can define their own boundaries and maintain polarity. As both pathways rely on the centrosome, studies to characterise these processes individually have been difficult. Disrupting the centrosome compromises both pathways while interrupting downstream components of either pathway results in masked phenotypes due to effective cell polarisation via the other pathway.
To overcome the functional redundancy that makes studying the microtubule-dependent pathway difficult, I have utilised a functionally null mutant of the gene, nop-1, which lacks early actomyosin flows to then screen for regulators of the microtubule-dependent pathway of polarity establishment, now required for embryo viability. Through this, and follow up immunofluorescent stains of polarity markers, I have identified novel proteins required for efficient cellular asymmetry. One such protein was the chromokinesin, KLP-19, previously known to aid chromosomal alignment and segregation during metaphase/ anaphase of
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meiosis and mitosis. I have shown that KLP-19 is required to keep the centrosome restricted to the posterior pole during polarity establishment, necessary to facilitate a robust symmetry breaking signal and ensure centrosome separation occurs in a timely manner for the setup of the mitotic spindle. It is likely that KLP-19 performs this role by localising to, and crosslinking, centrosomal and cortical microtubules that meet in an antiparallel manner
Mergers and Acquisitions in Sin Industries
Get PDFPh. D. ThesisMergers and acquisitions (M&A) have the potential to generate value for firms and their
shareholders by gaining synergy from targets. However, the empirical evidence suggests M&A
destroy firms’ value and shareholders’ wealth instead. The reason is that the acquirers are
overwhelmingly motivated by value-decreasing motives (e.g., market-timing, empire building).
The sin industries (e.g., tobacco, alcohol, and casino) are different from other industries due to
their harmfulness and devastative consequences to society. Because of this characteristic, sin
industries are stigmatized and neglected by society and investors. This negative attitude towards
sin industries poses a significant negative impact on sin businesses (e.g., elevating the cost of
capital, see Hong and Kacperczyk, 2009). Accordingly, it is essential for sin firms to improve
their images. Shedding light on this behaviour, this thesis examines performance and motives
of sin M&As in the G20 countries from 1993 to 2017. We show that sin firms try to improve
their images by making value-increasing acquisitions. In relative terms, the sin acquirer market
returns are more favourable than non-sin acquirer returns. Moreover, prior literature shows
evidence that societal attitudes towards sin industries differ across countries. Classifying the
G20 sample into high and low social norm countries, we extended prior literature by examining
how social norms impact sin and non-sin firm M&As.
We explore three angles of sin mergers and acquisitions: short-term market reaction to M&A
announcements, long-term performance after acquisitions, and the motives behind M&A
decisions. In the first empirical chapter, we find that the sin acquirer cumulative abnormal
returns (CAR) at M&A announcements are more favourable than non-sin acquirer CARs. The
difference in CARs across sin and non-sin acquirers is further elevated in high relative to lowsocial-norm countries, where people are less concerned about the negative consequences of sin
industries than other countries.
In the second empirical chapter, we find that the long-term operating performance of sin
acquirers are not improved. However, the sin acquirer’s shareholders gain significantly positive
returns in the long-term after acquisitions. Moreover, the sin acquirer returns are more
favourable than non-sin acquirer returns. Interestingly, the difference in returns across sin and
non-sin acquirers is further elevated in high relative to low-social-norm countries.
In the last empirical chapter, we find that sin acquirers are inspired by market-timing and
synergy motives. However, sin acquirers are less motivated by market-timing than non-sin
acquirers. The difference in market-timing motive between sin acquirers and non-sin acquirers
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is greater in high-social-norm countries, where people are more concerned about the negative
effect of the sin industries
In conclusion, we find evidence that the sin firms improve their image by involving in better
M&A deals than non-sin acquirers. As a result, the market reactions to M&A announcements
of sin acquirers are more favourable than for non-sin acquirers. As there is no differential impact
on operating performance, the more favourable return of sin acquirers likely derives from their
better motives (i.e., less market-timing). Interestingly, the difference in market performance
and motives across sin and non-sin acquirers is further elevated in high relative to low-social norm countries