Clinical characterisation of the cardiovascular effects of targeted anti-cancer therapies

Abstract not currently available

Bayesian hierarchical methods for non-standard compositional data

Compositional data take the form of parts of some whole, consisting of sets of non-negative components. Compositional data can appear as proportions, percentages, general non negative values or counts. The inherent characteristics of compositional data, i.e. non negativity and the constraint to some total, pose unique challenges for traditional statistical techniques. Compositional data arise across many real-world applications such as health, environmental, forensic, financial and sports science. Further challenges occur when compositional data also include other advanced data challenges such as multilevel hierarchical structure, non-smooth time series or a spatial structure. The main technique in the literature to overcome the complexities of compositional data is to transform the components from the simplex (the sample space of compositional data) into Euclidean space (the standard statistical space) using a log-ratio transformation. Once transformed, standard statistical models can be applied. However, while this transformation is powerful, it is not always suitable in practice. There are many features commonly found within compositional data that prohibit log-ratio transformations. For example, when compositional data contain zeros, the log-ratios become undefined. Similarly, when the components contain missing values, some or all of the log-ratio transformations may not produce sensible results. Lastly, when compositional data consist of counts, applying a log ratio transformation may discard information on how the total count may impact the variance and the possible values the counts can take. Thus, there is a need for frameworks that can handle compositional data containing these features, as well as addressing advanced data challenges. This thesis presents novel Bayesian hierarchical frameworks designed to overcome the limitations of log-ratio transformations in these instances. We apply and evaluate our proposed frameworks to three applications of compositional data containing both a feature which prevents log-ratio transformations and an advanced data challenge. These include: compositional data containing many zeros and a multilevel hierarchical structure, applied to forensic elemental glass data; non-smooth time series containing a count structure and zero values, applied to COVID-19 variant counts; and compositional data with a spatial pattern containing zeros, applied to tree species proportions across a spatial grid. We assess the performance of our frameworks through both in-sample and out-of-sample predictive experiments, comparing with commonly used models. The results from the predictive experiments demonstrate the effectiveness of our approaches, highlighting their contribution to compositional data analysis and offering a robust alternative for handling real-world compositional data

Topological insulator material for high frequency generation

Abstract not currently available

From metonymy to metaphor: A diachronic corpus-based comparison of metaphorical meanings of English and Chinese colour terms

Cross-cultural comparisons of metaphors mostly take the form of synchronic research (e.g. Kövecses 2005). However, diachronic research contributes not only to revealing cultural factors of one language (e.g. Gevaert 1995) but also to investigating universal trends (e.g. Trim 2014). Colour metaphors are appropriate subjects to investigate the interplay of similar conceptualisation (even potentially universal trends) and cultural specificity because of the common metonymic relationships to the universal natural world and culture-specific symbolism of colours. This thesis compares English and Chinese colour metaphors and analyses the similarities and differences in the metaphorical conceptualisation and ongoing development of metaphorical expression. It investigates five pairs of English and Chinese colour terms with the same etymological metonymies (green, orange, rose/rosy, purple, gold(en) and their Chinese counterparts qing/lv, cheng(se)/juse, meiguise, zi, jin(se)), and three pairs with different etymological metonymies (pink, peach(y), beige and their Chinese counterparts fen(hong)(se), tao(hua)se, mise), in order to investigate the interaction between metonymy and metaphor in the development of both English and Chinese colour metaphors. This thesis uses a corpus-based method of collecting metaphorical senses of colour terms from historical corpora in four periods of English and Chinese respectively, to reveal and compare the routes taken during the course of their metaphorical development. The corpora are supplemented by other resources – dictionaries, the Historical Thesaurus of English, and Mapping Metaphor with the Historical Thesaurus. The results show that colour metaphors develop from connotations of colour in a process that moves from metonymy to metaphor. The study suggests that the metaphorical conceptualisation of colour terms starts from an experiential scene that generates connotations associated with colour. The generation process has three main motivations: metonymic basis, cultural context and relationship with other colours. Then, the connotations are generalised to a distinct domain outside of the experiential scene and finally develop into metaphorical meanings. The similarities are motivated by the potentially universal patterns both in the generation process (which give rise to the same connotations of the same metonymic bases) and in the generalisation process (which trigger the shared generic conceptualisations of metaphorical mappings). The potentially universal pattern in colour metaphors also reveals another kind of potentially universal human experience relating to the environment other than embodiment as the experiential bases of potential universal metaphors. The differences are driven by culturally motivated patterns in the generation process and generalisation process, which give rise to culturally specific connotations and metaphorical mappings

Investigating gene expression patterns and amino acid metabolism in CML LSCs using transcriptomics and ex-vivo expansion

Chronic myeloid leukaemia (CML) is a myeloproliferative disease where a normal haematopoietic stem cell (HSC) undergoes chromosomal translocation, leading to the formation of the Philadelphia chromosome (Ph). The Ph contains the fusion oncogene breakpoint cluster region abelson murine Leukemia 1 (BCR::ABL1), which encodes a constitutively active tyrosine kinase. BCR::ABL1 signalling transforms a HSC into a leukaemic stem cell (LSC), which is responsible for propagating CML. Tyrosine kinase inhibitors (TKIs) have vastly improved patient outcomes in the long and short term, however BCR::ABL1 inhibition alone is insufficient to eradicate all disease causing LSCs. Bulk transcriptome profiling is a method which has been used to study CML LSCs for over 20 years, and has revealed much regarding the phenotype and molecular features of the LSC. Recent advances such as single cell transcriptomics have again increased the granularity at which we understand LSCs, now providing the capacity to phenotypically identify BCR::ABL1+ LSCs, predict treatment responses, and identify features of treatment resistant LSCs. Metabolomics and transcriptomics have also shown that LSCs possess enhanced metabolism compared to their HSC counterparts, with metabolic adaption also being a mechanism by which LSCs are capable of surviving TKI treatment. Therefore, we aimed to conduct a metaanalysis on CML LSC transcriptomic datasets to determine if we could identify novel BCR::ABL1+ specific signals and metabolic genes across phenotypes, ranging from CD34+ to CD34+CD38-CD90+CD26+ cells. Additionally, we aimed to use recent advances in ex-vivo HSC culture and apply them to LSCs, to identify the metabolic weaknesses of murine CML LSCs, and validate these findings in-vivo. In our meta-analysis, we show numerous uncharacterised genes differentially expressed in LSCs compared to bystander BCR::ABL1- or normal HSCs across datasets and phenotypes, and a core of commonly expressed genes that would likely represent meaningful therapeutic targets. We also observed widespread changes in all areas of metabolism, particularly OXPHOS, amino acid (AA) and fatty acid metabolism in Lin-CD34+CD38- LSCs. While we detected fewer changes within the Lin-CD34+CD38-CD90+ compartment, we were still able to detect metabolic changes, suggesting this weakness is present even in a highly primitive phenotype. To assess the utility of ex-vivo culture methods, we conducted hibernation culture and poly-vinyl alcohol (PVA) based expansion culture on CML LSCs. We found that the low number of LSCs that could be purified from leukaemic mice made hibernation culture a challenge when considering hypothesis testing, even though it may be more physiologically relevant. Using PVA based ex-vivo expansion, we were capable of expanding LSCs from a c-kit enriched or sorted population under normoxia or hypoxia. We then used expanded LSCs to conduct an AA dropout screen, wherein LSCs were grown in media individually missing each of the AAs. Among the top hits were valine, leucine and isoleucine (the branched chain amino acids (BCAAs)), which we further characterised using a combination of expanded LSCs and cell lines. We found BCAA restriction in-vitro to be highly efficacious, with a 75% reduction in BCAA concentration having a strong anti-leukaemic effect in both cell lines and expanded cells. We also show that BCAA restriction reduced ex-vivo expanded HSC growth substantially. Lastly, we used dietary restriction of BCAAs to treat murine CML in-vivo, however, the combination of BCAA restriction and CML was poorly tolerated, and so we could not detect any anti-leukaemic effect

Diagnosis and phenotypes of coronary microvascular dysfunction

Abstract not currently available

Sporting heritage: what value does it hold?

Sport has been at the heart of popular culture in Glasgow for over a century. Our relationship with sport as a player or a spectator has the power to stir the heart and mind; it has the power to evoke memories that are often infused with sound, sight, smell and taste; it has the power to unite us. The city’s integral relationship with sport was demonstrated recently when it agreed to host the Commonwealth Games 2026 after Victoria, Australia withdrew due to rising costs. Yet, for an activity that plays such a dominant part of our lives sporting heritage is an area that is just starting to gain interest and further research in the heritage and archaeology sector. The case studies that follow will explore the value of sporting heritage to the citizens of Glasgow. It will investigate the demanding campaign taken by the people of Govanhill when their sporting heritage was under threat; the Edwardian Baths which was the only social and leisure facility in the area was considered too expensive to keep open by the council. Govanhill Baths opened in 1917 became a vital part of the community’s public health system as it was not only a place where working-class people could access washing facilities but also a hub for public swimming and leisure activities. The struggle to preserve their historical sporting structure ensued for over twenty years and is now a symbol of the community’s strong identity and cohesion. The second case study will explore the historical sporting hub of Glasgow Green and the West Boathouse which is located on the banks of the River Clyde within the park. The Green is one of Glasgow’s oldest and most notable spaces regarding sporting heritage and is inherent to the development of many sporting clubs such as football, golf and rowing. Built in 1905, the Edwardian West Boathouse housed the Clyde and Clydesdale Amateur Rowing Clubs, which have both greatly contributed to Glasgow’s legacy in rowing. However, by 2015 the building faced significant structural problems and was in a perilous condition. The significant renovation and upgrade of the building ensured the continuation of rowing on the Clyde as an important social and competitive sport. Additionally, the extensive community engagement programme which ran in conjunction with the restoration encouraged a new audience to re-engage with the river and celebrate the east end of the city’s rich sporting culture and heritage. The final case study follows the rise of skateboarding which was initially an alternative sport in the 1970s and 80s and gained traction as a countercultural movement. Kelvingrove 1978 skatepark played a vital role in this youth subculture as it was a unique space for young skaters to challenge the conventional ideas of sport and recreation through creativity, expression and identity. The skatepark was covered over by 1982, at a time when boarding had taken a dip in popularity however preliminary archaeological investigations are enabling a better understanding of Glasgow’s post-industrial transition. This research will demonstrate the potential for further archaeological exploration of the site to appreciate the creation of new communities and cultural identities in the urban landscape and how public spaces evolved to meet these new societal trends

Synthesis and characterisation of Fe(III) and Co(II) complexes: a magnetic study

Abstract not currently available

Characterisation of therapeutic approaches for Alzheimer's dementia in the APP mouse model - neurotrophic factors and sensory stimulation

Abstract not currently available

Improving multi-phase performance of a Coriolis Flowmeter

In this dissertation, a new concept is introduced to improve the multi-phase flow metering performance of an existing Coriolis Mass Flowmeter (CMF) by sensor fusion with an additional differential pressure sensor. Core element of the concept is an empirical functional group of so-called acceleration factors that characterize the correlation of pressure drop over other flow parameters, mainly liquid mass flow rate and amount of entrained gas. In order to establish these correlations, experimental and numerical data have been produced, analysed and processed. This was done within the laboratory of the predevelopment department of Endress + Hauser Flow in Freising, Germany. The measurements contain a large matrix of flow parameters, vertical as well as horizontal orientations and a step-by-step increment of geometrical complexity. First, the multi-phase pressure drop over single straight tubes was investigated and compared to the current state-of-the-art. Next, an interim stage between the simple geometry of a single straight tube and a CMF was taken by producing and modelling a straight double tube with a true to scale flow splitter that divides the flow into two parallel tubes and merges them back together further downstream, an element highly similar to the inside of a CMF, but without its characteristic bent shape. Lastly, the experimental approach covered the true CMF geometry and was carried out with water-air and glycerine-water-air mixtures as well as complemented by auxiliary investigations regarding the recirculation zone. The findings of this research make it possible to deploy an iterative algorithm to quantify the liquid mass flow rate of a multi-phase flow for entrained gas contents of up to 30% in volume for Reynolds numbers in the range of 300 to 300,000. Further extension of the validation to a larger parameter range is not ruled out, but was not possible to investigate due to the limits of the laboratory. A meaningful statement about the accuracy of the overall algorithm should only be given after a field test, however the prediction of the acceleration factor functional group appears to be in the range of ±10 % accuracy with most data points with higher Reynolds numbers appearing in the ±5 % accuracy range. Furthermore, the results of this work can be used for further studies of CMF multi-phase behaviour