VictorJuiz/thesis huggingface dataset:
Evolutionary modelling of biological structures
Keywords: Bayesian
Evolution
RNA structure
Probabilistic
Protein structure
Phylogenetics

Many naturally occurring biological molecules, such as nucleic acids or proteins, are evolutionary related, having evolved from a common ancestor via a process of sequence mutation. Mutations undergo a process of selection, with combinations of mutations that preserve or improve a molecule's fitness having a higher probability of being maintained. Mutations that modify structure are expected to particularly impact fitness, and often detectably influence observed patterns of mutations.
Nucleotide coevolution is one such example, whereby pairs of nucleotides within biologically functional nucleic acid secondary structures exhibit evidence of coevolution that is consistent with the maintenance of canonical base-pairing. PINNACLE, the first of two models developed in this dissertation, is a sequence evolution model that assesses the rates of mutation associated with base-paired sites in alignments of DNA or RNA sequences. PINNACLE is able to fully account for an unknown secondary structure, and in doing so can be used to predict a secondary structure shared amongst an alignment of sequences. PINNACLE was used to infer rates of coevolution associated with GC, AU (AT in DNA), and GU (GT in DNA) dinucleotides in non-coding RNA alignments, and single-stranded RNA and DNA virus alignments. Strong evidence was found for GU dinucleotides being selectively favoured at base-paired sites in non-coding RNA and RNA virus alignments, with slight evidence for GT dinucleotides being selectively favoured at base-paired sites in DNA virus alignments. The strength of coevolution at base-paired sites in a SHAPE-MaP-determined HIV-1 NL4-3 RNA secondary structure and a corresponding alignment containing large numbers of HIV group 1M sequences was also measured, finding statistically significant correlations between the experimentally-determined SHAPE-MaP pairing scores and the inferred degrees of coevolution.
The second model developed in this dissertation, ETDBN, differs from typical evolutionary models in that it models the structural evolution of proteins in addition to their sequence evolution. ETDBN uses a dihedral angle representation of protein structure, and models the evolutionary trajectory between a pair of protein structures using an angular diffusion process on the two-dimensional torus. ETDBN is trained on a large database of proteins, and is parameterised such that it can learn the dependencies between sequence and structural evolution. The model has interpretable parameters, and is comparatively more realistic than previous stochastic models of protein structure evolution. Using the trained model, we were able to identify apparent sequence-structure evolutionary motifs present in numerous homologous protein pairs. The generative nature of our model enabled us to evaluate its validity and to infer various quantities, such as protein structures or alignments from sequences of amino acids, dihedral angles, secondary structure labels, or any combination thereof.
Ergodic and algebraic properties of transfer operators for products of random matrices
Keywords: Transfer operators
Lyapunov exponent
Products of random matrices
Operator algebra

A recent paper by Pollicott in 2010 presented an efficient algorithm for computing the Lyapunov exponent of i.i.d. random products of positive matrices. The aim of this thesis is to generalise some of the aspects of Pollicott's approach to Markovian and more general matrix products using the theory of transfer operators. Some minor mistakes in Pollicott's original paper are corrected in the thesis. The possibility of further generalising the algorithm using the theory of operator algebras is discussed in the last chapter.
Reproductive microbiotas of the red junglefowl, Gallus gallus: Patterns and drivers of variation
Keywords: Microbial Ecology
Red Junglefowl
Seminal Microbiota
Behavioural Ecology
Reproductive Microbiota
Cloacal Microbiota
Microbiota

Organisms host diverse and complex bacterial communities (microbiotas), often with fundamental roles in host ecology and evolution. While microbiotas of the gut have received considerable research focus, relatively little is known about reproductive microbiotas, (i.e. those communities living within the reproductive tract and potentially transmitted at mating), despite the potentially critical role they may play in host sexual selection and mating system evolution. This thesis seeks to address this gap by laying the foundations for the systematic study of reproductive microbiotas in bird populations, and the patterns and drivers of intra- and inter-individual variation. I studied a captive population of red junglefowl, Gallus gallus, a sexually promiscuous species with well-characterised mating systems. Developing a pipeline based on a next-generation sequencing approach I show that junglefowl ejaculates contain diverse bacterial communities of bacteria (seminal microbiotas), which reflect the gut microbiota and vary in structure across males. I then use in vitro culturing to demonstrate that seminal microbiotas are alive and ecologically complex. Next, focusing on patterns of variation in seminal microbiotas, I show an association between inter-male variation in composition and aspects of the male immune-genotype, and find evidence that variation in seminal microbiota structure might be influenced by the sexual dynamics of social groups. Finally, I focus on the female cloacal microbiota and the potential effects that insemination of male semen might have on these communities. Using a series of controlled artificial insemination experiments, I show some evidence that the microbiota of the female cloaca appears to be disrupted by the first inseminations, but might revert back to its initial structure following cessation of inseminations. These effects might be due to the disruption caused by the insemination, rather than by the transmission, and subsequent colonisation of male bacteria. Collectively, these results demonstrate an ecologically complex and dynamic avian reproductive microbiota, providing a platform and direction for future work, by emphasising the need for an understanding of composition, function and variation in reproductive microbiota in order to better understand microbiotas and contextualise the evolutionary ecology of host mating systems.
Radiolabelled Bacillus anthracis toxin-based probes for molecular imaging of MMP activity in tumour models
Keywords: Matrix metalloproteinases activity
cancer
anthrax lethal toxin
SPECT

Increased activity of matrix metalloproteinases (MMPs) is associated with poor prognosis and metastasis in different cancer types. To exploit this feature and target cancer cells, the protective antigen (PAWT) of the binary anthrax lethal toxin (LT) was modified to form pores in cell membranes only when cleaved by MMPs (PAL1). Anthrax lethal factor (LF) is then able to translocate through these pores into the cytosol of tumour cells. The aim of this work was to develop a novel non-invasive imaging agent for the detection of matrix metalloproteinase (MMP) activity based on engineered variants of LT. Here, 111In- radiolabelled form of LF was used with the PAL1/LF system to allow non-invasive in vivo imaging and quantification of MMP activity in tumour tissue by SPECT.
Initially, PAL1 MMP-activation was tested in a cell free assay. Subsequently, the activation of PAL1 was evaluated by a cytotoxic assay in a range of cancer cell lines, with or without a broad spectrum MMP inhibitor. MMP2 and MMP9 activity in the different cancer cells was assessed by gelatin zymography. Expression levels of MMP14, and LT native receptors (TEM8 and CMG2) were evaluated by western blot analysis. LT components were radiolabelled with 111In. Cell abundance of TEM8 and CMG2 was determined by saturation binding assays using 111In-radiolabelled PAWT. After 111In-radiolabelling non-toxic variants of LF, their cell uptake was evaluated in the presence or not of PAL1. Evaluation of the in vivo pharmacokinetics and biodistribution of 111In-radiolabelled LT components was performed by SPECT/CT in naive mice or MMP-expressing MDA-MB-231 tumour-bearing mice.
PAL1 MMP-cleavage was confirmed in a cell free assay. Notably, PAL1 capacity to cause cytotoxicity in a panel of cancer cells correlated with anthrax toxin receptor and MMP14 expression. Additionally, in the presence of MMP inhibitors PAL1 mediated cytotoxicity was prevented. Selective delivery of 111In-radiolabelled LF variants to MMP-expressing cells by PAL1 was demonstrated in vitro, and corroborated using confocal microscopy with fluorescently labelled variants of LF. Dynamic SPECT imaging demonstrated superior and selective uptake of radiolabelled PAL1 in tumour tissue when compared to radiolabelled PAWT. Finally, a radiolabelled LF variant was selectively delivered to MMP-positive MDA-MB-231 tumour bearing mice by PAL1, presenting excellent target-to-background contrast.
Taken together, these results indicate that radiolabelled forms of mutated anthrax lethal toxin hold promise for non-invasive imaging of MMP activity in tumour tissue.
Spectral networks, abelianization, and opers
Keywords: algebraic geometry
quantum field theory
flat connections
supersymmetry
spectral networks

In this thesis we study a number of geometric structures arising in the study of four-dimensional supersymmetric quantum ﬁeld theories.
We study properties and applications of so-called “spectral networks” on Riemann surfaces C, focusing in particular on the “abelianization map” which we use to produce special coordinate systems on moduli spaces of local systems on C. We generalize the classical Fenchel-Nielsen coordinates and utilize these coordinates to compute superpotentials, following and generalizing a conjecture of Nekrasov-RoslyShatashvili.
Our ﬁrst result is a computation of the higher rank spectral coordinates associated to certain “generalized Fenchel-Nielsen” networks, yielding explicit formulas for the trace functions on the moduli space with two “minimal” and two “maximal” punctures. We use this result to verify the NRS conjecture at the lowest order asymptotics for a prototypical SU(3) theory, and furthermore compute the 1-instanton correction in the SU(2) case, extending previous results. In the ﬁnal chapter we include some partial results the author has obtained on the existence and uniqueness of abelianizations for certain classes of networks related to Grassmannians.
The religious world in late Ming China as seen through the 勵修一鑬 Lixiu yijian: how was Christianity integrated into the local society of Fujian?
Keywords: Lixiu yijian
Giulio Aleni

Past studies on expeditions by missionaries to Ming China have mainly focused on the doctrinal transmission of Christianity and examined how Chinese elite received and interpreted the Christian ideas. However, the aim of this paper is to shift the focus to the local sphere in order to explore how Christianity was “done” on the local level. In this respect, this study takes two arguments as a point of entry – both pioneering but very different in perspective. On the one hand, the French sinologist Jacques Gernet proposed a theory of “cultural incommunicability”, in that differences in philosophical framework and cultural history prevented local Chinese people from grasping the essence of the doctrine. As a consequence, Christianity “failed” to be transmitted to China.1 On the other hand, Erik Zürcher has asserted that Christianity integrated into the local community by becoming accommodated by both missionaries and local people, and localised to the pre-existing religious and social world. Following Zürcher’s argument, scholars such as Nicolas Standaert, Adrian Dudink, Eugenio Menegon, and Henrietta Harrison have produced important scholarship examining the different dimensions of local Christianity from Ming China onwards. In this paper, I will follow Zürcher’s argument of localisation and further discuss how Christianity integrated and transformed into a local religious practice, through looking at stories in the Lixiu yijian 勵修一鑬. In dealing with the notion of “religion”, I will be using Barend J. ter Haar and Adam Chau’s conception of religion as something that people “do” and “practise”. Chau has proposed “to look at the Chinese religious landscape through the lenses of ‘modalities of doing religion’ and ‘ritual polytropy’.” In brief, he argues that religions in China should not be studied as coherent conceptual aggregates, such as “Buddhism” or “Daoism”. Rather, we should look at how people “do” religion on the ground. Chau observes that China was characterised by ritual-based and polytrophic religiosity—people made use of different coexisting and competing ritual providers and liturgical programmes in order to acquire efficacious ritual services.2 In his studies on the Non- Action Sect, ter Haar argues that the sect initially emerged from a group reflection on the practices. Nevertheless, through closer analysis, he demonstrates that for people of the sect, the reading and reciting of the scriptures was the core religious activity. The religious experience was achieved not through a mere reflection on the texts, but, as the title of his book Practicing Scriptures suggests, through practice of the scriptures.
[introduction continues in thesis]
Toward a “two-war legion”: renegotiating First World War memory in the British and American legions, 1938-1946
Keywords: First World War
American Legion
British Legion
Memory
Ex-servicemen
United States
Britain
Veterans
Second World War

This thesis explores the renegotiation of First World War memory in response to the Second in a comparative study of two ex-servicemen’s organisations, the British and American Legions. Through a close reading of two organisational periodicals – the British Legion Journal and the American Legion Magazine – published from 1938 through 1946, this study examines how conceptualisations of duty and service, comradeship, and the social contract that were anchored in the First World War shifted as the Second unfolded. It extends existing scholarship by deconstructing the Second World War into its constituent events and charting First World War narrative shifts according to these developments in real time. In addition to highlighting the peculiarities of each national context, the project’s unprecedented use of the British and American Legions as comparative case studies illuminates common factors affecting the evolution of memory transnationally, specifically aging, generational shifts, and sub-national identities. According to these factors, certain narratives of the Great War came to be privileged over others, shaping the longer-term evolution of memory discourses for veterans who identified with that conflict. In both groups, discussions used the First World War as the definitive reference point for understanding the Second, framing the earlier conflict as a “learning experience”. The extent to which each country was seen to have learned from these “lessons” influenced the perceived significance and meaning of the Great War. The study sheds light upon the differing level of importance afforded to the First World War in British and American historical memory, arguing that the specific ways in which the conflict was used to understand its successor inflected and ultimately altered the war’s memory in both the British and American Legions.
Using practice theory to research energy and environmental governance for small and medium-sized enterprises
Keywords: climate change
SMEs
environment
environmental governance
energy

If the transition to a low carbon economy is to be successful, inclusive and sustainable, then small and medium-sized enterprises (SMEs) must not be neglected. However, they are extremely heterogenous and it is difficult to make generalisations about their motivations, consumption patterns or everyday practices, or to create effective policies and governance processes.
This social scientific research uses qualitative methods to investigate how and why energy is consumed by organisations, and the role of governance practices in shaping demand. The central research question is:
• How can practice theory be used to improve the effectiveness of UK SME energy and environmental governance?
Five empirical papers answer this question by applying practice theory in various settings:
• Paper 1 focuses on the practice of home and its affective dimensions. Themes of comfort, control and flexibility are revealed, each influencing how energy is consumed and conserved.
• Paper 2 combines practice theory with the concept of sensemaking to show how energy management is intertwined with organisational culture and knowledge construction processes in three SMEs.
• Paper 3 shows that low carbon SME advisors are critical middle actors, but could be more effective if ‘softer’ skills were deployed alongside technical expertise.
• Paper 4 combines practice theory with the multi-level governance framework to investigate policy implementation as a practice-bundle, spanning spatial and temporal settings.
•Paper 5 asks whether practice theory could follow behavioural economics in gaining influence within government. Findings indicate a need and appetite for practice-theoretical insights amongst government social researchers.
This research demonstrates how practice theory can help to improve the effectiveness of governance practices. However to gain greater influence, researchers need to be philosophically liberal, experimental in their use of theory and methods, and pro-actively develop relationships with governance actors at local and national levels.
The organisation and delivery of clubfoot treatment services in Malawi: an ethnographic study
Keywords: Clubfoot
Sub-Saharan Africa
Medical sociology
Qualitative
Malawi
Health service delivery
Ethnography

Background
Clubfoot is a congenital condition in which one or both feet are twisted inwards and if left untreated or ‘neglected’, can have a profound impact on the wellbeing of children and their families. Clubfoot can be treated through staged manipulation of the limb and treatment is delivered by Beit CURE Hospital in Malawi which coordinates 29 outreach clinics. However, implementing these services is complex; a high proportion do not present; and adherence to treatment is low. This study had three aims: 1) identify factors that impact on the implementation of services and develop a theoretical framework to inform findings; 2) understand the impact of accessing services on carers of children with clubfoot; and 3) explore the experiences of those who had not fully accessed treatment.
Methods
Ethnographic data collection comprised three elements. Element 1: Observation sessions were conducted at three clinics (totalling 90 hours) and interviews conducted with staff at an additional nine sites and members of the CURE management team. Key informants helped place findings within the wider health context (n = 58). Element 2: Fieldwork was conducted at three sites and involved single, dyad or triad interviews and focus groups with those currently accessing treatment, those who had been discharged and clubfoot counsellors (n = 57). Element 3: In-depth case studies were conducted with those that had not fully accessed treatment (n = 4).
Results
Factors impacting on service implementation were interpreted using an implementation science theory known as extended Normalization Process Theory. Factors identified included cooperation, commitment to delivery, workability and strategies to facilitate delivery over time. An additional construct identified concerned work done to facilitate patient access. How families and the community responded on finding out the child’s feet were different varied. Whilst some mothers received love and support from others, it could also be a source of conflict and division. Families were overwhelmingly satisfied with treatment although challenges were identified. Those that had been discharged described joy and were happy to be relieved of the financial burden of treatment. Factors that influenced treatment-seeking for those who had not fully accessed treatment included the anticipated outcomes of living with clubfoot, availability of social support networks, healthcare experiences and a lack of referral pathways for treatment. Challenges took place in a web of competing concerns such as poverty.
Conclusions
The study provides insights to help organisations in Malawi deliver more effective patient care. Future research should explore processes of identification and referral of children with neglected clubfoot.
Getting ‘the feel’: craft learning as perceptual transformation
Keywords: carpentry
learning
education
phenomenology
craft
Heidegger
perception
boats

Becoming a wooden boat builder requires ‘getting the feel’ for the tools and materials of the trade by learning to perceive these objects in terms of their practical purposes in the workshop. In this project, I explore such learning from a sensory-ethnographic perspective, journaling how my own perceptual experience transforms over six months of work building boats. To supplement this first-person method, I carry out participant observations and long-form interviews with boat builders, paying particular attention to the ways in which newcomers to the workshop are guided through the learning process. I interpret the rich accounts of learning that result through concepts from philosophy, exploring how the perception that I record can be seen to demonstrate a fundamental mode of human understanding. Using Heidegger’s idea of ‘being-in-the-world’, I show how learning entails a constant re-alignment of understanding through which individuals continually rediscover their human capacity for meaning-making. By investigating the link between perception and understanding in the craft workshop, I contribute to theoretical debates over the nature of human cognition while also illuminating the complex and often-overlooked cognitive processes that underpin practical work.

My findings show how ‘getting the feel’ entails learning to perceive practical objects in new ways, recognising aspects of tools and materials that are invisible to the unaccustomed viewer. In some cases, ‘the feel’ involves specific combinations of objects appearing together in terms of work that they perform, rather than separately as discrete entities. In other cases, it entails tools and materials appearing to transform, splitting apart or combining in perception as their defining practices demand. Throughout the investigation, I show how understanding varies between the three workshops, and how each contains its own mechanisms for introducing the newcomer to situated ways of seeing and feeling. Despite their differences, however, the workshops share three main modes of learning: self-motivated exploration, expert guidance, and participation in a community designed to reproduce the skills and understanding it requires of its future members. By continually participating in each of these three modes, boat builders accumulate expertise as they move between settings and progress within them, ‘getting the feel’ for gradually-shifting constellations of materials, people, and practices.