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Delivering immersive virtual reality as an intervention to patients with chronic low back pain in he Kingdom of Saudi Arabia: a mixed-methods feasibility study
Get PDFDevelopment Of a nanobody-conjugate platform for targeted drug delivery in airway hypersecretory diseases
Get PDFAirway Hypersecretory Diseases (AHDs) are conditions in which the main pathophysiology is mucus hypersecretion. The incidence of AHDs is high (over 500 million affected worldwide) and comes with a diminished quality of life for patients. Very few treatment protocols focus on mucus hypersecretion. We propose a nanobody-conjugate platform for the targeted treatment of AHDs based on nanobody targeting of goblet cell surface antigens and a site-directed conjugation method to allow therapeutics to be attached to the nanobodies.
A diverse synthetic nanobody library based on the shark vNAR 5A7 scaffold and expressed as N-terminal pIII fusion proteins within the phagemid pSEX81 was developed to create a naïve nanobody library displayed on M13-based bacteriophage particles, for screening. NGS analysis confirmed a diversity of 2.56 x 109, comparable to libraries described in the literature.
Human bronchial epithelial cells (HBEpc) were cultured at the air- liquid interface as a model for the human airway epithelium, and IL-13 stimulation was used to simulate the hypersecretory phenotype observed in AHDs. Flow cytometry analysis validated IL-13 driven airway remodelling, and goblet cells metaplasia. Increases in the percentage of goblet cells in culture were observed, similar to the effects reported in the literature (from 3.77% to 17.92% post IL-13 stimulation, N=3). A whole cell biopanning protocol was designed for phage display selection of potential binders to stimulated epithelial cells and yielded 8 clones. Sequencing of these clones revealed highly disturbed origin of replication and nanobody regions, and no binders could be identified.
Functionalisation of nanobodies by site-specific bioconjugation of a fluorescent tag was investigated. Sortase A catalysed coupling was selected as it allowed for the conjugation of the fluorescent label selectively at the C-terminus, preventing the labelling of the binding sites of nanobodies. A Cy5.5 label was synthesised by solid-phase peptide synthesis and amide coupling. The label encoded the oligoglycine recognition site of Sortase A enzyme, and the cyanine fluorophore was coupled to the side chain of a lysine. The original vNAR 5A7 was engineered to express the LPXTG recognition sequence of Sortase A alongside a poly-histidine tag for purification by immobilized metal affinity chromatography. Despite several optimisations of the expression protocol, the Hen egg white lysozyme specific vNAR 5A7 was not expressed in E. coli, and further work will be needed to produce the protein. The challenges of whole cell biopanning and nanobody expression and purification are discussed
Mathematical neuroscience: from neural fields to neuroimaging
Get PDFModern non-invasive techniques for probing human brain activity, such as magnetoencephalography (MEG), offer high temporal resolution and continuously improving spatial resolution, providing an increasingly detailed view of brain function. These advancements enable the development of sophisticated mathematical models to better understand the mechanisms underlying spatio-temporal neuroimaging signals. This thesis enhances the biological accuracy of neural mass, field, and network models by incorporating a variety of key biological features, improving their utility in understanding brain function. We make use of various neural models, including mean-field models derived from networks of single neurons, which allow for tracking neuronal synchrony and incorporating biological features such as gap junctions at the cellular level. A model incorporating dendritic depth allows more direct measures of local field potentials (LFP) and electroencephalography (EEG) signals. Furthermore, models integrating gap-junctions and extracellular ion concentrations are developed, providing insights into the relationship between extracellular activity and neuronal dynamics—a subject particularly relevant to epilepsy research. An optimisation algorithm is also developed and utilised to fit these models to real data
Evaluating the Effect of a Whole-Class Intervention to Enhance Mathematical Resilience and Reduce Mathematics Anxiety: A Mixed-Methods Study
Get PDFResearch shows that mathematics anxiety (MA) can appear early in formal education in the UK. Although early intervention has been identified as important for reducing MA and improving positive long-term outcomes, universal strategies in primary schools have received little attention until now. A structured approach aimed at fostering mathematical resilience (MR) has emerged as a promising method for helping learners manage and reduce MA. This study examines the effectiveness of integrating key principles of this approach into a whole-class MR intervention in primary schools, focusing on the “Growth Zone Model” (GZM) and its practical application in the classroom.
A cohort of Year 4 children and their teaching staff participated in this research. A sequential explanatory mixed-methods study was conducted. Phase one of the research employed an AB single-case experimental design (SCED), where school staff delivered a whole-class MR intervention to their Year 4 class over thirteen weeks. Six pupil participants were selected for SCED analysis, based on initial high levels of MA. Subsequently, in phase two of the research, qualitative interviews were conducted to explore perceptions regarding the implementation of the intervention. Semi-structured interviews were conducted with the six focus children, along with a focus group of the school staff who facilitated the intervention.
For three of the six focus children, there was an overall decrease in the mean level of MA and an increase in MR between the baseline and intervention phases. Tau-U analysis demonstrated a statistically significant improvement in self-reported MA (p < .05) for one of the focus children. From phase two of the research, five themes emerged from the data concerning the teacher and teaching assistants, as well as the six focus children’s, perceptions of the whole-class intervention. The identified themes emphasised the intervention’s role in fostering reflections on teaching and learning culture, enabling timely responses to children’s academic and well-being needs, and supporting self-regulation to enhance behaviour for learning. Additionally, the findings highlighted the intervention’s feasibility and a desire for broader implementation.
Overall, the research presents some promising outcomes regarding a whole-class MR intervention, with staff advocating for its implementation at a whole-school level. The study highlights the potential for further investigation and advancement of whole-class approaches to support children with MA
Kinship connections and the Earldom of Orkney c. 900–1263
Get PDFThis thesis investigates the kinship connections of the Orkney earldom from literary and historical perspectives. Using Social Network Analysis tools, this thesis considers the connections between the 500+ individuals featured in Orkneyinga saga. It discusses what the kinship connections in Orkneyinga saga tell us about how the text was constructed and how the kinship connections of the Orkney earldom changed over time. Chapter 1 examines how and why kinship connections were made, drawing on perspectives from other sagas, contemporary societies, and network theory. Chapter 2 explores how these relationships were memorialised, considering the relationships between genealogical information, laws, literature, and the landscape. Chapters 3 and 4 are a close analysis of the kinship connections in Orkneyinga saga. Chapter 3 focuses on connections within the earldom, while Chapter 4 examines connections to foreign powers. Chapter 5 builds on this analysis to highlight people linked to the family networks of the text who are well positioned to have been informants for Orkneyinga saga. This thesis illustrates that earls of Orkney used different kinds of kinship connections for different political purposes. It finds that kinship connections were remembered for various reasons: to structure sagas, or to create a sense of prestige or identity. It argues that Orkneyinga saga is a partial account of Orcadian history, told from the perspective of a select few families. Finally, it suggests that Orkneyinga saga is a repository of family traditions which were transferred to saga compilers in Iceland and Norway through informants related to the people in the text
Deep Eutectic Solvents: Properties and Protein Interaction [Part A] BSA in Urea-Sarcosine DES: Solubility, Aggregation, and Storage Stability [Part B]
Get PDFPart A
In recent years, green solvents have emerged as an alternative to replace toxic organic solvents, deep eutectic solvents (DESs) is a new type of green solvents which have a great development prospect. They are mixtures of two compounds which have a lower melting point due to their unique physicochemical properties. This kind of new green solvents can be used in many fields because of their low toxicity and become more and more popular. Deep eutectic solvents are formed through hydrogen bonding between the hydrogen bond donor (HBD) and the hydrogen bond acceptor (HBA) and have more advantages than traditional ionic liquids and organic solvents. They have
many applications in drug delivery and protein extraction. The main physicochemical properties of them have been studied are phase behaviour, viscosity and density in this paper. Moreover, they can interact with protein through several mechanisms which are hydrogen bonds, hydrophobic interactions, salting out effects and electrostatic forces. These mechanisms influence the structure and function of proteins. Additionally, urea and sarcosine are also useful in DES system. In conclusion, DES is a new generation of green solvents and show a wide application prospect in the field of protein science.
Part B
This study investigated the effects of a urea-sarcosine deep eutectic solvents (DES, molar ratio 5:2) at different water contents (50% and 80%) on the solubility, aggregation behaviour, and storage stability of bovine serum albumin (BSA). Results demonstrated that this DES system formed a stable homogeneous liquid, with viscosity and density increasing as water content decreased, while pH remained neutral. At attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) confirmed the formation of a strong hydrogen-bond network in the DES. BSA solubility in the DES increased with rising DES content. Dynamic light scattering (DLS) and analytical
ultracentrifugation sedimentation velocity (AUC-SV) revealed that DES effectively inhibited BSA aggregation, demonstrating excellent stability protection particularly under high-temperature (40°C). The 80% water content DES exhibited optimal anti-aggregation efficacy at elevated temperatures. AUC analysis further indicated that 80% water content DES promotes reversible self-association behaviour in BSA, whereas this phenomenon was not observed in 50% water content DES. This study confirms that urea-sarcosine DES is a green solvent which can enhance protein stability, demonstrating potential for application in biotechnology field
On fuzzy analogues of physical spaces in noncommutative geometry
Get PDFSince the development of noncommutative geometry, it has become common to construct fuzzy versions of well-known geometric spaces, such as the fuzzy sphere. This work follows efforts to construct approximations to physical spaces that are as consistent as possible with the definitions of a spectral triple. The first part looks at a way of constructing lattice-like spectral triples that are able to approximate simple geometries such as the line and the circle. The latter model is successfully interpreted in terms of a fermionic state-sum model with a U(1) connection. The second and main part of the work develops a model for a fuzzy complex projective plane within the formalism of matrix geometries, itself a formulation of real spectral triples in terms of matrices. An argument is presented that justifies the expectation that such fuzzy spaces with symmetry groups may by necessity approximate coadjoint orbits. A Hilbert space and Dirac operator that approximate the complex spinor geometry of the complex projective plane are then constructed, which are much simpler and more concrete than those obtained by earlier efforts in the literature
Essays on political economy: evidence from Brazil
Get PDFThis dissertation is composed of three empirical essays on public economics and mostly political economy. The first essay studies fiscal spillovers. The second essay studies the impacts of banning local party branches from forming pre-electoral coalitions. Finally, the third essay, which is my Job Market Paper, refers to firms' political connections in Brazil.
The first essay examines fiscal spillovers across Brazilian municipalities by exploiting quasi-random variation in federal transfers. Using an event study design, I test whether a jurisdiction’s sudden increase in revenue, generated by discontinuities in the allocation of central government transfers, affects the fiscal and economic behavior of its neighbors. The results show positive spillovers on neighboring municipalities’ public expenditures and local labor markets. These additional expenditures are primarily financed through federal education transfers, triggered by increases in population. The findings highlight how fiscal interdependencies and demographic dynamics can amplify the effects of intergovernmental transfers beyond their immediate beneficiaries.
The second essay investigates the impacts on local political assemblies from a Brazilian reform banning local party branches from forming pre-electoral coalitions. We confirm prior research findings of a large immediate reconciliation of local party systems with a sharp drop in the number of small, personalistic parties. We test a series of pre-registered hypotheses about subsequent consequences for party systems, parties, and individual politicians. Contrary to our predictions—reduced party system fragmentation did not forego reductions in electoral volatility or reductions in politicians’ (sky-high) rates of party-switching behaviors. We discuss why the reform seemingly failed to strengthen these important dimensions of local democracy.
The third essay, my Job Market Paper, analyzes the economic returns to political connections in Brazilian local elections, focusing not only on traditional campaign donations but also on two novel channels: firms that provide goods or services to candidates during campaigns and firm owners affiliated with parties within a coalition running for mayor. Employing regression discontinuity and event study methods around close mayoral races, we find that politically connected firms substantially increase both their likelihood of securing procurement contracts and the value of those contracts, though without corresponding gains in employment or wages. This essay contributes to the literature on political connections by documenting the emergence of indirect political connections and public procurement allocation in a context of weak institutional constraints
Flexible embedded actuation packs for continuum robots:enabling extra-long exploration of narrow environments
No full textBenchtop to bedside: developments in pulmonary MRI
Get PDFThis work focuses on two distinct methods for pulmonary MRI: the development of contrast-based hyperpolarised noble gases production techniques and the implementation and application of free-breathing 1H-based functional imaging at 0.5 T. An overview of the thesis and a list of published works are provided in Chapter 1, followed by four novel research chapters.
Established Spin Exchange Optical Pumping (SEOP) polarisers typically specialise in polarising a single noble gas isotope. Chapter 2 follows the construction and testing of a versatile preclinical polariser, able to produce large volumes of hyperpolarised 129Xe, 83Kr and 131Xe. The SEOP process necessitates the dilution of the hyperpolarised species and subsequent purification is required to maximise SNR; however, hyperpolarised krypton cannot be purified by established cryogenic-based methods. Therefore, Chapter 3 follows the engineering development of a novel purification apparatus for hyperpolarised 129Xe and 83Kr, using molecular hydrogen as a buffer gas, which is eliminated through controlled combustion with oxygen.
The established Phase resolved functional lung (PREFUL) methodology is typically employed with 1.5 T MRI, limiting its deployment with scanners with an open architecture and in developing countries where low field systems are typical. In Chapter 4, the PREFUL algorithm is adapted in a custom-built pipeline for application with low field (0.5 T) MRI, accounting for a lower SNR and imaging rate. Conventional MRI scanners limit participants to lying horizontally, therefore these investigations do not account for changes to the lung due to gravity. In Chapter 5, the PREFUL pipeline is employed with Open MRI to probe changes in the distribution of lung ventilation and perfusion in different postures. This is the first MRI study to investigate the lungs in the inverted position
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