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Zoonotic barriers: defining species-specific porcine restriction factors against coronaviruses
No full textThe pandemic nature of coronaviruses (CoVs) is underpinned by their ability to mutate
and overcome barriers caused by evolutionary differences between species and establish
disease in new hosts. One such barrier is the interferon (IFN) response. Systematic
analysis using arrayed human IFN-stimulated gene (ISG) expression libraries has been
effective at identifying antiviral factors. By comparing antiviral activity against viruses
adapted to different species, species-specific restriction factors have been identified that
act as barriers against zoonosis. However, most of these studies were focused on humans
and libraries for other species are lacking.
Pigs are important livestock species for public health as they are hosts of influenza
virus and at least six CoVs. We have generated an arrayed lentiviral-based porcine
Type-I ISG expression library comprising 432 ISGs to enable cross-species screening. We
hypothesized that a pig endemic virus would be more adept at evading the IFN response
of the natural host, compared to a virus, such as SARS-CoV-2, that has not adapted to
pigs. Indeed, our results indicate that porcine respiratory coronavirus (PRCV), a highly
adapted endemic CoV in pigs that causes pneumonia resembling SARS in humans, was
less sensitive than SARS-CoV-2 to porcine IFN. This suggests species-specific restriction
factors have greater antiviral effects against non-adapted viruses. To identify such
factors, we have applied the library to PRCV and SARS-CoV-2. We have developed
and optimised resources to carry out such screening experiments in porcine cell lines,
as existing protocols for human cell lines were not applicable. Using an RT-qPCR-based
read-out, we have identified and validated two novel porcine ISGs, ZCWPW1 and
PHACTR1, which potently restrict PRCV and SARS-CoV-2 replication. We also showed
that the ISG, USF1, restricts SARS-CoV-2 to a greater extent than PRCV.
In addition to the IFN response, receptor compatibility could be a major determinant
in the lack of susceptibility of pigs to SARS-CoV-2 in vivo. Human ACE2 is the entry
receptor for SARS-CoV-2. We have developed a human ACE2 transgenic pig model
highly susceptible to SARS-CoV-2, displaying clinical signs, disease progression, and
lung inflammation that faithfully replicates COVID-19 in humans. This large animal
model could serve as a unique tool in addition to non-human primates and rodents
for testing mechanisms of disease and developing improved vaccines and therapeutics
against COVID-19
Exploring care home mealtime experience: perspectives during the COVID-19 infectious disease outbreak
Get PDFMealtimes are fundamental to residents’ lived experiences and are pivotal moments in their everyday routine lives in care homes. How mealtimes are planned and enacted and how mealtime experiences are perceived are considered important phenomena in care home settings. Several factors influence residents’ experiences, including infectious disease outbreaks. More recent research has focused on the epidemiological or public health impact of the COVID-19 outbreak in care homes. However, there is currently no way of knowing about the influence that infectious disease outbreaks have on care home mealtime structure and residents’ mealtime experience, which this study aims to address.
This study uses a qualitative social constructionist approach to explore the influence that infectious disease outbreaks, primarily COVID-19, have on care home mealtime structure and residents’ mealtime experience. To understand how mealtime experience was constructed, 11 semi-structured interviews and observations were conducted with care staff and residents in three care homes in Scotland. Data collection occurred in two phases between April 2021 and April 2022. Nine of the interviews were with care staff online, and two were face-to-face with residents.
The findings, after thematic analysis, highlight the negative impact that COVID-19 had on three main aspects of residents’ mealtime experience: norms and routines, social interaction, and the interconnectedness of the care home community. Significant changes in how mealtime was structured in the care homes during the pandemic led to participants’ negative perceptions of their mealtime experience. An interesting finding from the study was that infectious disease outbreaks may influence participants’ perception of their mealtime experience more significantly than the structure of mealtimes in care homes. What this means for care home residents’ mealtime experience is a balanced approach to policy decision-making that keeps residents safe while ensuring the quality of their lived experiences
The negotiation of identity in English for academic purposes: investigating international students’ experiences in a Scottish university context
Get PDFIncreasing globalisation and student mobility have given rise to an agenda of
internationalisation within Scottish universities. Concerns that the Covid-19 pandemic would
precipitate a decline in international student numbers highlighted their importance for
Higher Education Institutions (HEIs), in terms of both reputation and financial health.
However, the diverse needs of this cohort are still not fully appreciated, and more research is
needed into their experiences.
For many international students, the first point of contact with their chosen university is a
pre-sessional course in English for Academic Purposes (EAP). The main goal of such
instruction is to familiarise them with the language and skills required for university study in
an Anglophone environment. Despite the growing provision of pre-sessional pathways, EAP
students have been neglected in the literature, especially as regards their linguistic practices
and identity development. In particular, there is a lack of understanding about how they
manage the transition into mainstream tertiary education.
The impetus for my study derives from teaching on pre-sessional EAP programmes and
wishing to know more about students’ perceptions of their time in Scotland. The main aim
was therefore to capture the experiences of a group of international postgraduates by
following them over time. Drawing on the theories of investment (Norton, 2013), positioning
(Davies & Harré, 1990) and cultural capital (Bourdieu, 1977), I investigated their identity
negotiation in different academic, linguistic and social situations. To the best of my
knowledge, no tracking studies of this kind have previously been conducted in a Scottish
context.
The mixed-methods study took place in a Scottish university which attracts a high number of
international students. An initial online survey was administered to a cohort of
postgraduates undertaking its pre-sessional EAP programme to gather their views and
demographic information. Following this, 11 focal participants were recruited for three indepth
interviews. Further interviews were conducted with EAP tutors (n=7) and academic
staff (n=7), and observations of EAP lessons also took place. Findings were analysed
thematically, and data from the quantitative and qualitative phases were integrated to
provide more detailed insights.
Several key categories were generated in the course of thematic analysis. These included:
adapting to unfamiliar expectations, perceptions of challenges, classroom participation,
changing identities and social interactions. Postgraduate participants’ responses
demonstrate that they experienced different interactive and reflexive positioning in the EAP
and degree programmes. They also encountered more dynamic fluctuations in identity over
time, as they tried to come to terms with new expectations. Findings reveal that EAP tutors
made efforts to increase learners’ confidence, but harboured doubts about how they would
be viewed in mainstream university classes. Although academic staff interviewees appeared
willing to accommodate and support students from overseas, concerns were raised about
the need to adapt their pedagogy.
The study makes a contribution to knowledge in terms of reconceptualising how
international students with a first language other than English are perceived. It adds to a
shift away from positioning them as deficient and instead brings their own agency and
cultural capital to the fore. There are implications for how we understand the experiences of
individuals from diverse cultural and educational backgrounds. It is proposed that dialogue
with both university staff and home students would lead to an improved awareness of the
benefits of intercultural exchange. Further collaboration between EAP tutors and academic
lecturers is also recommended. Such steps could help to ensure that international students
are treated as legitimate members of the academic community, rather than as problems to
be solved
The legal and economic boundaries of corporate group structures: the UK company law debacle of the corporate form
Get PDFThis thesis critically examines the interplay between shareholder incentives, powers, and the externalisation of risk in the framework of UK company law, with a focus on corporate groups. It tackles fundamental questions surrounding the legal structure of companies and its ramifications for third-party interests. The questions explored include the mechanisms through which shareholder incentives intersect with company law, the impact of corporate group structures on risk externalisation, and the effectiveness of existing legal frameworks in addressing these issues. By highlighting the disconnect between theoretical premises and real outcomes within company structures, this thesis seeks to examine the real-world consequences of shareholder-driven risk externalisation by the use of the corporate form. While many have researched corporate groups from a doctrinal perspective to highlight gaps in group regulation, this thesis uniquely addresses these gaps through theoretical lenses.
Chapter 1 lays the groundwork by considering the inherent incentives for externality within company structures and the development of shareholder privileges. Chapter 2 evaluates the mechanisms through which shareholders use the corporate form to transfer risk onto external parties, particularly unsecured tort creditors. Chapter 1 and 2 highlight the disconnect between theoretical concepts and business realities, revealing how legal doctrines inadvertently facilitate risk externalisation.
Chapter 3 explores the role of corporate group structures in exacerbating this issue. By dissecting the complexities of corporate groups, this thesis reveals how their structure(s) enables parent companies to exploit legal and economic principles by controlling the group, receiving its benefit, and shielding its assets from liabilities, leaving the subsidiaries’ unsecured creditors vulnerable. In corporate groups, shareholder incentives generated by the corporate form are significantly amplified, potentially increasing at an exponential rate. This escalation of incentives can lead to a higher risk of externalisation due to the compounded effect of using multiple corporate forms.
In chapter 4, various legal mechanisms, which could have the effect of mitigating externalities, are scrutinised yet found inadequate. Both internal solutions to company law and external solutions found in other areas of law are not effective in resolving the issue. Ultimately, the issue lies in the use of the corporate form, which, due to its conceptual underpinnings, inadvertently incentivises risk externalisation. Therefore, a more comprehensive exploration of its theoretical foundations is imperative to understand and address these systemic challenges.
Chapter 5 critically evaluates prevailing theories of corporate personality, revealing also their limitations in addressing risk externalisation. The fine points of chapter 5 emphasise the need to reassess theoretical company law to provide solutions to the externalisation of risk stemming from the corporate form. The analysis of theories, such as the concession theory, aggregate theory, and real entity theory, reveals their limitations in adequately recognising the complexities of corporate groups and the consequences of their actions. By showing how these theories fail to account for the economic and social impacts of corporate activities and their interconnectedness within groups, this chapter advances the importance of reorienting company law towards a deeper understanding of corporate functions and their implications. By advocating a broader consideration of economic and social consequences, it calls for a reconceptualisation of company law beyond the narrow confines of legal boundaries.
In exploring alternative regulatory approaches, in chapter 6, this thesis proposes the adoption of the enterprise theory as a supplement to traditional legal entity theories. By emphasising the economic realities of corporate structures and advocating in favour of collective accountability, it bridges the gap between corporate legal theory and practical implications. Ultimately, this thesis advances a holistic understanding of corporate groups that transcends traditional boundaries; by aligning the corporate and organisational forms, it aims to foster a more heightened accountability of corporate groups
Airport security workforce planning
Get PDFUncontrollable passenger arrivals cause frequent situations where passenger demands
exceed the available capacity. This becomes particularly apparent within the airport’s
bottlenecks — such as the security hall — where long queues can build up, leading to
delays, which translates to unhappy passengers and airlines. Planning for and quickly
adapting to changes in passenger arrivals to the security hall and staff availability is
key to keeping a consistent flow of passengers and avoiding a build-up of queues.
This problem can be addressed at different stages in the roster planning timeline.
At the strategic planning stage, the chief staff scheduler (CSS) and HR department
can change contracts and adapt the workforce structure (e.g. via recruitment) best to
suit the expected demand for the upcoming season. At the tactical planning stage, the
problem is two-fold. On the one hand, a fast and flexible roster tool is needed to adapt
quickly to changing work regulations and union demands. On the other hand, this is
the last time the CSS can freely allocate workforce members to the schedule. Hence,
they need to use this chance to build flexibilities into the roster that can help adapt to
changes in demand at the subsequent operational planning stage.
A solver-independent modelling approach using Mixed Integer Programming and
Constraint Programming is proposed as a fast and flexible Roster Tool to support the
CSS’s decisions and help with union discussions. Based on this tool, a Simheuristic is
derived to allocate flexibility to the roster at the tactical planning stage. The
Simheuristic combines a metaheuristic (Simulated Annealing, Genetic Algorithm and
Adaptive Large Neighborhood Search (ALNS)) to adjust the flexibility metrics in the
roster with Monte-Carlo Simulation of demand patterns and staff absences that need
to be addressed. The proposed Simheuristic for tuning flexibility metrics is the first of
its kind in rostering literature. It shows significantly better results than simply
adjusting the aggregation of the demand forecast into a model week.
Furthermore, a Simheuristic consisting of ALNS to adjust the contracts and
Monte-Carlo Simulation to test the feasibility of the resulting rosters is proposed to
address the strategic planning problem of finding the best contractual combination for
the next season. The experiments suggest that different demand patterns require
different workforce structures, which implies that the airport should revisit its
contracts every season to best address expected changes in passenger demands.
Finally, a case study of Edinburgh Airport’s security staff scheduling problem and
the development of a suitable rostering approach is presented
High precision tools for intraoperative brain cancer therapy
Get PDFGlioblastoma remains to be the most aggressive brain malignancy to affect adults. The disease has a median survival of only 15 months, owing to tumour recurrence within 2 cm of the primary tumour site. Despite the poor prognosis, standard treatment still relies heavily on surgical resection of the tumours, followed by chemotherapy with temozolomide and radiotherapy. This treatment is hindered by the vast heterogeneity within and between glioblastoma subtypes. In this work, the author has proposed the use of photodynamic therapy as an adjuvant to surgical resection. Photodynamic therapy utilises light to induce a reaction between a photosensitiser and molecular oxygen in order to initiate cell death. This technique centres on three main components; the photosensitiser, light and oxygen. Each of these, in themselves, are non-toxic and cell-death is only elicited when all three are combined.
While there are promising candidates for the treatment of glioblastoma through photodynamic therapy, these photosensitisers are often bulky molecules which lack specific targeting groups. This results in side- and off-target effects as well as patient-dependent differences in dosage in the target tissues at the time of treatment. Therefore, a library of photosensitisers based on the nitrobenzoselenadiazole (SeNBD) scaffold was designed. By taking advantage of the low molecular weight of SeNBD, this photosensitiser was readily conjugated to other small molecules, with the overarching aim of targeting glioblastoma metabolism. While differential uptake of metabolites was not effective enough to discriminate between healthy and cancer tissue, a further level of control was added through the design of an activatable photosensitiser. This was achieved by disrupting the electron density within the scaffold, thus quenching the absorbance of the photosensitiser.
The nature of these quenching groups can be altered to tune the stimulus which uncages the photosensitiser. As a result, a library of orthogonal and environmentally sensitive photosensitisers based on SeNBD has been created, and this approach applied to other photosensitive scaffolds (i.e. 2-thioxocoumarin, thionaphthalimide, Nile Blue and methylene blue). This highlights the modularity of the approach and the wider implication on developing activatable photodynamic therapy agents.
Combining these two strategies paves the way to the development of some of the first enzyme activatable, metabolically targeted photosensitisers. As a model, a cathepsin B sensitive pro-fluorophore was synthesised based on the ONBD scaffold. Transcriptomic data from glioblastoma stem cells (GCGR-E17, GCGR-E31, GCGR-E57) and healthy foetal controls (GCGR-NS12ST_A, GCGR-NS17ST_A, GCGR-NS9FB_B) suggest that this approach can provide an effective route to selective ablation of glioblastoma cells without significant damage to surrounding healthy tissues
Professionals and Presbyterians: a historical organization studies enquiry into how the city of Edinburgh sustained itself as an important financial centre for three centuries
Get PDFThe City of Edinburgh has been a significant financial centre for 300 years. It
pioneered modern banking and the widespread use of banknotes. It was where life
assurance was invented and developed. It mastered the management of the
investment trust and channelled vast quantities of British investments into everything
from American railroads to Malaysian rubber plantations. And yet it was in the wrong
place, too small, politically isolated and with nothing approaching the manufacturing
or trading base of other British cities. What was its secret? Since the Global
Financial Crash of 2008, some of its best-known institutions have failed. This thesis
however concentrates on periods before that, asking what went right rather than
what went wrong. It is located in the relatively new discipline of Historical
Organization Studies, drawing on the work of Pierre Bourdieu, on Strategic Action
Field theory, and on developments in micro-history. In so doing it answers the long-standing call to bring historical analysis into organization theory and contributes both
to history, through original research, and to theoretical development through the
application of theory to fresh historical data
Investigating oxidative stress responses in Trypanosoma brucei and Trypanosoma congolense bloodstream forms
No full textAfrican trypanosomes are parasites spread by tsetse flies that cause severe diseases in humans and animals. The clinically relevant species include Trypanosoma brucei, upon which the majority of our biological understanding is based, and T. congolense, which is less understood. These parasites are extracellular in all stages of their complex life cycle, as a result, they are continuously exposed to harsh environments in their mammalian and insect hosts. In the mammalian host, the immune system is characterised by key innate immune cells such as macrophages, which release reactive oxygen and nitrogen species, imposing oxidative stress. The parasite response to oxidative stress, as well as redox balance maintenance, have been studied to some degree in T. brucei, but not in T. congolense, which is known to exhibit divergence at the genome, transcriptome and metabolome levels. Understanding these responses and how they differ between closely related species is crucial for uncovering parasite survival strategies and developing therapeutic interventions.
This thesis investigates the hypothesis that oxidative stress responses and redox balance mechanisms differ between bloodstream forms (BSFs) of T. brucei and T. congolense, and that these differences underlie phenotypes such as differential sensitivity to oxidative stress and interactions with macrophages. Specifically, it examines the oxidative stress responses, redox balance mechanisms, and interactions with macrophages in these two species to determine their differential parasite sensitivity. Techniques including metabolomics and transcriptomics were used to compare genes and pathways involved in these processes between the two species that may explain any observed phenotypic differences and similarities. Finally, the thesis also explored a gene linked to oxidative stress resistance previously studied in the parasite Leishmania, but not yet explored in African trypanosomes.
To facilitate the study of the two trypanosome species under comparable conditions, a novel lipid-rich medium, Morrison’s Universal Medium (MUM) was developed and optimised. This medium enabled the direct comparison of redox balance and oxidative stress response pathways between T. brucei and T. congolense. Experiments were carried out to find suitable candidates for inducing oxidative stress under in vitro conditions, which led to the identification of the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) as a viable candidate. Subsequently, experiments with SNAP showed that T. congolense was more sensitive to nitrosative stress compared to T. brucei. In vitro studies on trypanosome-macrophage interaction further supported these findings, as T. congolense viability was reduced to a greater extent in the presence of macrophages.
To investigate potential underlying metabolic differences that could explain the differences in SNAP sensitivity, a comparative analysis of intracellular and extracellular metabolites of T. brucei and T. congolense was carried out using cells derived from the same medium. It was found that both species showed a similar capacity for glucose consumption, in contrast to previous data showing that T. congolense had reduced capacity. Metabolomics data further showed that T. brucei excreted high levels of pyruvate while T. congolense consumed this metabolite, indicating a species-specific difference in pyruvate utilisation. T. brucei culture supernatants consistently showed elevated acetate levels, which was not consistent with previous literature. Taken together, these results are indicative of metabolic adaptation to MUM. T. brucei supernatants also exhibited higher levels of immunomodulatory aromatic ketoacids such as indolepyruvate, hydroxyphenylpyruvate and phenylpyruvate. Conversely, T. congolense exhibited higher levels of antioxidant metabolites, such as glutathione, oxidised glutathione, and ornithine, which help protect cells from damage.
Metabolomics data were integrated with previously generated transcriptomics data, highlighting that T. congolense exhibited a higher expression of genes associated with the trypanothione cycle and polyamine biosynthesis – pathways that play a role in handling oxidative stress. Moreover, T. congolense displayed a higher transcript abundance of genes linked to the oxidative branch of the Pentose Phosphate Pathway (PPP), which produces antioxidant components. In contrast, T. brucei showed higher activity of genes from the non-oxidative branch of the PPP, which are involved in energy production. Combined, the data indicated that T. congolense has more activity in oxidative stress response pathways compared to T. brucei, even under steady-state conditions.
Studies in the related kinetoplastid parasite Leishmania spp. showed that overexpressing the gene aconitase (ACO) increases resistance to nitrosative stress. The role of this gene in nitric oxide resistance has not been investigated in African trypanosomes. I, therefore, investigated the impact of ACO overexpression in T. brucei and T. congolense BSFs on SNAP sensitivity. Overexpressing ACO in T. congolense caused BSF parasites to differentiate into a form resembling the insect stage procyclic forms (PCFs), suggesting a role for ACO in parasite differentiation. In contrast, overexpressing ACO in the monomorphic T. brucei Lister 427 led to significant mortality without any morphological change, likely because this strain is incapable of differentiation. Analyses, including adaptation to PCF culture media, flow cytometry, and microscopy, confirmed that ACO overexpression caused T. congolense to differentiate into a form closely resembling PCFs. I was unable to evaluate the role of ACO in oxidative stress management across both species, which warrants further investigation. In addition, further work is required to determine the mechanisms by which ACO overexpression is linked to differentiation.
In summary, this thesis presents the development of a universal medium enabling the culture of multiple African trypanosome species. This system revealed T. congolense’s increased sensitivity to oxidative stress compared to T. brucei and highlighted metabolic similarities and differences between species. Additionally, this thesis describes the potential role of ACO in promoting differentiation in trypanosomes. These findings offer valuable insights into the adaptive mechanisms of African trypanosomes, and further support a growing body of literature evidencing biological divergence between two closely related species of clinically relevant protozoan parasites
The Shifting Landscape of Iraq’s Judiciary: Increased Judicial Activism, Centralisation and Politicisation after 2017
No full textThis paper examines the evolution of Iraq’s judicial system after 2003, focusing on the increasing centralisation of judicial power and the rise of judicial activism. Following the fall of Saddam Hussein, the judiciary has become progressively insulated from criticism, with power concentrated within the Supreme Judicial Council (SJC). This consolidation has allowed the judiciary to expand its role beyond impartial justice administration, engaging more actively in political processes and increasing its susceptibility to political influence. The findings of this paper suggest that post-2003 judicial reforms, while ostensibly aimed at fostering judicial independence, have instead led to the creation of a judiciary that is often seen as playing a political role and serving the interests of the leading Shi’a political elite. This has worked to compromise its intended neutrality and poses a risk to the rule of law in Iraq
Settler colonial humanitarianism: a genealogy of the settler subject in Palestine/Israel
No full textThis thesis reorients settler colonial studies towards an understanding of humanitarianism’s role in the constitution of the settler subject. Grounded in the case of Palestine/Israel, the settler colonial modality of humanitarianism that I illustrate is two-fold: enabling the continuous establishment of the settler society; and providing a tool for the dispossession of Palestinians. To substantiate these central claims, I draw from a genealogical methodology that reconstructs the changing patterns and spaces in which humanitarianism came to shape the settler subject, tracing its appearance and evolution to present day. To trace this genealogy linking different historical moments to the present, I relied on research in multiple archives and over 60 interviews conducted primarily during fieldwork in Palestine/Israel.
The global history of humanitarianism in colonial and settler colonial contexts tells us a story in which it is usually the native subject the recipient of humanitarian aid and sentiment. But archival research on the relief work of the Zionist Commission (1918-1921), which targeted settlers in need of aid to rebuild damaged colonies, reveals a distinct form of settler colonial humanitarianism which breaks from that historical pattern. After the First World War, humanitarian relief transformed into an instrument of settler sovereignty formation within the bounds of British imperial rule. Meanwhile, in revisiting the 1948 Nakba (catastrophe), I argue that the 1923 precedent on Greek-Turkish ‘population exchanges’ influenced how the expulsion of Palestinians was framed as a ‘humanitarian’ population transfer. This moment opens an avenue for understanding humanitarianism’s function in the dispossession of Palestinians. Yet, at this historical conjuncture, for the Israeli statehood project to succeed the mass depopulation of Palestinians that took place in 1948 had to be coupled with populating the conquered land with settlers. Here I argue that the ‘humanitarianisation’ of the Jewish immigration process facilitated the creation of the Israeli settler state.
Drawing from an ethnographic approach and interviews with Israeli settlers, Israeli military officials, and staff of international humanitarian organisations, I explore the contemporary manifestations of the settler subject through two different processes. First, I examine a recent form of humanitarian governance adopted by the Israeli military which serves to buttress the control, counterinsurgency strategies, and ultimately dispossession of Palestinians. Second, a close appraisal of Israeli settlers evacuated from Gaza in 2005 reveals the multiple ways in which a settler colonial form of humanitarianism emerged. Israeli settlers began mobilising the figure of the refugee and the mental health discourse of trauma to disavow the process of de-settlement from Palestinian land. Through a reconstruction of the historical and contemporary contours of Israeli settler colonialism, this genealogical investigation thus shows how humanitarianism generates an eliminationist settler subjectivity that heralds the removal and replacement of Palestinians
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