VictorJuiz/thesis huggingface dataset:
A multiple comparative study of test-with development product changes and their effects on some attributes of team speed and product quality

While studying Test-First Development (TFD), researchers have typically compared it to Test-Last Development (TLD), across groups or projects, and for relatively short durations. But, we have observed that teams testing fine-grained changes do not necessarily develop tests for those changes first. And, comparing across groups or projects is difficult, due to the "contextual variables" specific to each. Finally, many "real-life" projects have long durations.
Because of TFD’s potential to increase team speed or product quality, and because of these previous limitations, we were motivated to design and execute our own related study. Our work on this study has resulted in three original contributions to knowledge: (1) our software change model; (2) our measurement method; and (3) our study results.
First, as part of our software model, we defined Test-With Development (TWD) as more general than TFD, and as a step that can be practised to a degree. Then, we defined team speed measures for a developer's product change: initial net size, discards over time, and net size over time. As well, we adopted product quality measures for a developer's product change: change in the number of potential bugs and change in the average method complexity.
Second, we defined a measurement method which allowed us to perform two studies, across six open-source projects and thousands of developer changes. With it, we performed an auxiliary study to calibrate our discards over time measure. Then, we used it to perform our main study to compare the effects of TWD product changes on some attributes of team speed and product quality.
Finally, the results from our main study indicate that there were significant differences between the effects of TWD product changes. We interpret these results to indicate that teams that practice TWD can increase their efficiency, by reducing their product’s complexity faster.

Advisor: Martin, A
DNA replication with an unnaturally large replicon in Saccharomyces cerevisiae

Eukaryotic cells co-regulate DNA replication and the cell cycle, ensuring a single round of replication occurs during each cell cycle. Until a few years ago, origin licensing and subsequent activation was considered to be a stepwise activation process, dependent on cell cycle kinases. However, it is now known that some phosphatases also play a key role in regulating DNA replication. A potential role during DNA replication initiation for the phosphatase subunit Rts1 was examined. Temperature-sensitive replication initiation mutants were examined to determine if synthetic rescue resulted when RTS1 was deleted (indicating antagonistic functions). It was shown that Rts1 did not antagonise origin licensing or activation. Conversely, RTS1 was found to have negative genetic interactions with CDC9, DBP11 and CDC45.
Re-initiation of replication origins (re-replication) has been associated with tumorigenesis; however, the opposite phenomenon (under-replication) has been less well studied. Potential outcomes include single-stranded DNA protection, alternative replication mechanisms, chromosome breaks, ‘fragile sites’ and/or cell death. This project aimed to create a system containing an unnaturally large replicon of over 100 kb, and characterise the resulting effects on cell growth and DNA replication.
DNA replication was delayed in the absence of adjacent active origins. However, mean generation time was not always extended. A next-generation sequencing approach, utilised to examine replication fork direction, indicated that replication forks could initiate close to telomeres despite origin inactivations, termed telomeric initiation.

Advisor: Nieduszynski, C
Norbury, C
Studies of genetic variants in monogenic renal tubular disorders

The renal tubules are the functional unit of the kidneys, responsible for: reabsorption of many substances including ions, solutes and water; and the secretion of waste products. The molecular mechanisms underlying these processes are tightly regulated by transporters, channels and receptors, which have different expression profiles within the renal tubular segments and their disruption can lead to disorders, with local and systemic phenotypes. Thus, monogenic renal tubular disorders affecting different segments are excellent tools for the study of specific pathways and mechanisms vital to reabsorption and secretion processes; as well as for gaining an insight into the biological and molecular differences between renal tubular segments. This thesis used next generation DNA sequencing (NGS) and Sanger DNA sequencing methods to identify novel candidate genes, and hence to study the genetic and molecular mechanisms underlying three monogenic renal tubular disorders: Dent’s disease (DD), familial juvenile hyperuricaemic nephropathy (FJHN) and familial hypocalciuric hypercalcaemia (FHH), each affecting different renal segments. For each of these disorders a large proportion of patients (25-55%) lack mutations in any of the known associated genes. However, one of the main issues with NGS remains accurate variant interpretation and therefore, the first aim was to investigate the effectiveness of in silico analysis tools to identify pathogenic variants and to determine the optimum parameters, which were then applied to the ‘gene-discovery’ studies. This thesis identified novel candidate genes for DD (CLCNKA), FJHN (CLDN3 and DENND4C) and FHH (KLOTHO) and revealed an approach for its potential successful application in the clinic for diagnosis.

Keywords: Renal tubules
Familial Hypocalciuric Hypercalcaemia
Familial Juvenile Hyperuricaemic Nephropathy
FJHN
Kidney
FHH
Monogenic disorders
Mutation analysis
Dent's disease
Variant analysis
Advisor: Piret, S
Humble geopolitics: rethinking natural hazards in South Iceland

This thesis is concerned with the ways that communities in South Iceland are negatively affected by their geologically active environment. I argue that contemporary theorisations of hazards in human geography retain a militaristic preoccupation with catastrophe, antagonism and annihilation that actively impedes a fuller attention to the ways that communities live with hazards. In this thesis, I develop a new set of theoretical concepts which together map out the dimensions of what I term a ‘humble geopolitics’ of natural hazards. Humble geopolitics draws attention to the complex spatio-temporal, non- catastrophic dimensions of geo-tectonic hazards and brings into relief the partialities of official programmes of hazard management in Iceland. I show the value of this reformulated geopolitics by working this concept through three empirical case studies that explore the role of a museum, citizen science and local community groups in catalysing experiences of earthly volatility and configuring modes of public response to it. These case studies illuminate the different space-times in which hazards are experienced, the diverse practices through which public participation is expressed and the different logics that underpin everyday modes of hazard governance. In the conclusion, I argue that this work opens up important new avenues for the geographical study of natural hazards, human geography more broadly, and for disaster risk reduction policy.

Keywords: Natural hazards
Disaster studies
Ethnography
Heimaey
Westman Islands
STS
Environmental geography
More-than-human geography
Iceland
Advisor: Lorimer, J
Greenhough, B
Kama, K
The systematic seed anatomy of the meliaceae - with particular reference to the seed-coat of the melioideae

Detailed and original descriptions and illustrations of the seed anatomy (especially that of the seed-coat) are presented of the tribes Turraeeae, Melieae, Trichilieae, Guareeae and Sandoriceae. Homologies of the seed-coat strata are established as far as possible, the taxonomic utility of each of the many characters assessed for each tribe and the taxonomic implications gauged using Pennington and Styles’ (1975) generic monograph of the Meliaceae as a basis.
Seed-coat characters seem particularly useful in several cases of generic delimitation and show great promise at the infra-generic level, their characters being relatively constant at the species level, but showing great variation between species. At the tribal level, they seem to be of less use in delimitation than do morphological characters but, nevertheless, do give an indication of affinities.
Particular attention is paid to the systematic anatomy of 'arillate' and 'sarcotestal' seeds in the Meliaceae and an attempt is made to establish a nomenclatural basis for fleshy seed types in the family. The phylogenetic implications of seed-coat characters are discussed at length on a generic and tribal basis and the functional significance of fruit and seed anatomical characters examined as far as is possible.

Keywords: seed-coat
meliaceae
seed
anatomy
systematic
melioideae
Modelling laser-plasma interactions for the next generation of high-power laser experiments

Investigating new regimes of laser-plasma interactions requires advances in at least two technologies: targets and laser systems. Exploring these regimes includes developing diagnostics to obtain more information about complex systems such as inertial confinement implosions and constructing models that consider entirely novel and unexplored phenomena.
This thesis initially considers implementing state-of-the-art "mid-density" targets made of foam on current petawatt-class laser systems; particularly the application of foams to ion acceleration. It is highlighted that foam targets potentially pave the way for laser systems to realise collisionless shock acceleration as a high energy quasimonoenergetic ion source. A theoretical approach modelling the predicted energy distribution function for shock-accelerated ions is presented with both classical and relativistic formulations. The full, albeit narrow, parameter space for collisionless shock acceleration is mapped and it is shown that there are several pre-existing laser systems that could realise high-energy narrow-band proton beams.
Impending multipetawatt laser systems are then considered but it is immediately highlighted that the absorption processes in this new regime may not be fully understood. Therefore, the thesis segues into developing a theory that models absorption in the newly dubbed
post-ponderomotive'' regime. One absorption mechanism, the Zero Vector Potential process is given a complete description, the predictions of which are validated through numerical simulations.
This discussion then considers the limit of the post-ponderomotive regime where quantum electrodynamic effects are predicted to be perturbations. The theory is modified to include the effects of electron-positron pair production and, again, a simulation campaign verifies the theory.
Applications of the Zero Vector Potential mechanism to coherent x-ray generation are also explored, and in particular their potential use generating warm dense matter. Finally, given that no scientific hypothesis can be considered valid until it has been tested through experiment, three experimental designs are proposed that could test the theories and hypotheses presented herein.

Advisor: Norreys, P
Channels and circuits: biophysical and network models of neuronal function

Neuroscience research studies the brain at various different levels of detail. Experimental work explores everything from the molecular machinery within each neuron, to the behavioral output of an organism. Similarly, computational models are designed to operate at many scales, and can address different questions depending upon the complexity of the description.
Detailed biophysical modelling incorporates findings about neuronal physiology and structure in order to test hypotheses and generate predictions. However, due to the complexity and number of modelling studies, it is difficult to compare models and to assess biological fidelity. In this work we present a curated database of nearly 3000 voltage-gated ion channel models used in published neuronal simulations, called ICGenealogy. Furthermore, we present a standardized formulation for ion channel dynamics which we fit to all models on this database. Through these two endeavors, we facilitate better experimentally-constrained modelling, while also providing insight into the diversity and complexity of ion channel dynamics seen in single neurons.
At a higher level, neuronal network models integrate findings about neuronal activity and cell types in order to explain representations and computations. Here, we present a model of context-dependent associative memory, which incorporates known principles of memory function from psychology research and proposes concrete functional roles for different components of neural circuits. Through analytics and simulations, we show that a contextual memory system not only provides benefits for memory capacity and robustness, but also enables control of memory expression. This work provides new conceptual ideas for memory research, suggests functional roles for different inhibitory cell types, and may help us to understand the interaction of different memory systems in the brain.
Together, the work presented here spans two distinct levels of detail and addresses current challenges both in biophysically detailed models, as well as computation in abstract network models.

Keywords: ion channels
associative memory
Advisor: Vogels, T
PIERCE1: a determinant of left-right asymmetry in mammals

The study of mice with heart and situs defects can provide useful models for improving our understanding of congenital heart defects in humans. This project characterised the involvement of 1700007K13Rik (PIERCE1) in left-right patterning. A proportion of homozygotes with a mutation in this gene were identified by the International Mouse Phenotyping Consortium as exhibiting situs inversus totalis and heart defects, which are indicative of faulty left-right patterning. We hypothesised that this gene is involved in the establishment of ciliary motility at the embryonic node. Motile cilia are also found in the trachea, and if the tracheal cilia of knock-out mice also have motility defects, C9orf116 (the human orthologue of 1700007K13Rik) may be a new candidate gene for primary ciliary dyskinesia, a heterogeneous recessive condition.
The evaluation of nodal ciliary motility and nodal flow in mice homozygous for a Pierce1-null allele demonstrated that aberrant motility, leading to a lack of effective leftwards nodal flow, underlies the left-right patterning defects in these mice. In addition to this, studies of tracheal ciliary and sperm flagellar motility showed that PIERCE1 is required for correct motility in all classes of motile cilia and flagellar evaluated. Transmission electron microscopy studies point towards a role for PIERCE1 in the assembly or trafficking of dynein arms and their components; however, protein interaction studies have proved inconclusive thus far at placing PIERCE1 within the network of known dynein arm assembly factors.

Advisor: Norris, D
Srinivas, S
Novel assessment of cardiorespiratory interactions in aortic stenosis

The outcome in aortic stenosis (AS) depends on the correct timing of aortic valve replacement. Currently, this is based on symptoms and cardiac response to pressure overload. In patients with multiple medical conditions, uncertainty exists concerning their symptomatic onset and in distinguishing cardiac from respiratory causes of breathlessness. An accurate assessment of lung disease and optimal tools to discriminate between cardiac and respiratory dyspnoea are needed in AS, in whom decompensation may confound respiratory assessment, and conversely, chronic obstructive pulmonary disease (COPD) is a major reason for delay or avoidance of surgery. Advanced imaging allows the assessment of cardiac and respiratory co-morbidities, potentially reducing the misinterpretation of symptoms, and, therefore, may enable more appropriate treatment in cardiopulmonary disease.
The thesis explores the importance of lung disease in AS and the limitations of standard respiratory assessment in decompensated cardiac disease. Secondly, novel ways of discriminating between respiratory and cardiac effects in AS are assessed. Lastly, the importance of the right ventricular response to pressure overload is evaluated. In summary, this thesis demonstrates the role of cardiorespiratory assessment in cardiac disease, including novel morpho-functional imaging evaluation of the cardiopulmonary interactions in AS. Patients with advanced lung disease who would not improve after valve replacement may in the future avoid a high-risk futile intervention. On the contrary, those with a hyperdynamic right ventricle and apparent respiratory dysfunction determined by cardiac disease might avoid cardiac under-treatment.

Keywords: Emphysema
Right Ventricle
COPD
Imaging
CMR
Aortic Stenosis
Xenon
Valvular Heart Disease
Aortic Valve Replacement
Cardiopulmonary
Cardiovascular
Dyspnoea
CT
Cardiac Function
Advisor: Myerson, S
Bafadhel, M
The visual vernacular: the canonization and celebration of the Uganda martyrs as a mark of post-conciliar change in the Catholic Church

The Uganda Martyrs have grown to become one of the country’s most persistent national symbols throughout the last 130 years. They maintain a commanding presence in everyday life to this day, both as a symbol of the Christian faith and of Ugandan perseverance and character amidst hardship. This thesis seeks to examine the legacy of these martyrs as they took on an increasingly pivotal role in public discourse in the early years of Ugandan independence, as promoted and transmitted by the Roman Catholic Church (RCC).
Specifically, it tracks the lively and enthusiastic co-opting of the Martyrs’ story into the workings of the Second Vatican Council, and in the RCC’s concentrated post-Conciliar activity in the developing world in two critical moments: the canonization of the Martyrs during a session of the Council in 1964, and Paul VI’s subsequent visit to Uganda to bless the new shrines to the martyrs being built there in 1969. Both of these events provided ideal outlets for the RCC to display a new approach to Christianity in the developing world based on the liturgical reforms of the Second Vatican Council, which had concluded in 1965.
This thesis utilises a novel combination of visual and written source material, bringing together work on the Second Vatican Council, Ugandan postcolonialism, and modernist architectural theory. It seeks to combine written material, in the form of official RCC documents and European press coverage, with a variety of visual media. It relies on extended fieldwork and site visits conducted in the greater Kampala area in addition to European archival material. Ultimately, the story of the Uganda Martyrs provides a unique insight into the interaction point between the global RCC and the local Ugandan Christian community.

Advisor: Betts, P
Larmer, M
Elucidating the non-apoptotic role of the caspases in the Drosophila intestinal system

The deregulation of caspase activity and stem cell properties are often correlated with the appearance and propagation of cancer, including colorectal cancer. However, the caspase-dependent regulation of the intestinal system remains poorly understood. Taking advantage of the powerful genetic tractability of Drosophila melanogaster, I aimed to decipher the functional role of the caspases within the intestinal system, in addition to their role in tumour formation. In this thesis, I demonstrated that using an apical-caspase reporter, I was able to observe widespread and stereotyped patterns of caspase activation within the intestinal system. Furthermore, this activation was non-apoptotic and occurred in non-regenerative conditions. Upon conditional knockout of the mammalian caspase-9/2 orthologue, Dronc, in intestinal progenitors, I demonstrated that Dronc was required to restrain proliferation and prevent the premature differentiation of Enteroblasts into Enteroctytes. Additionally, this activity of Dronc relied on its catalytic activity but not the canonical apoptotic pathway. Using a Dronc-protein reporter I was able to correlate these functions with its specific accumulation within the Enteroblasts. Molecularly, the non-apoptotic activity of Dronc in this context relies on the activity of the Notch and Insulin-TOR pathways. Using the Drop-seq single-cell sequencing technique, I observed the misexpression of several regional and cell-specific genes following loss of Dronc. Furthermore, these Dronc-specific effects may result in the deregulation of the intestinal microbiota. Collectively, this data provides novels insights into the caspase-dependent but non-apoptotic regulation of the intestinal system in non-regenerative conditions. Furthermore, these findings could explain the correlation between caspase-9 misexpression and the bad prognosis observed in patients suffering from colon cancer.

Keywords: Intestine
Cancer
caspase-9
caspase
melanogaster
non-apoptotic
Cell Biology
Drosophila
gut
Dronc
Advisor: Baena-Lopez, A
How the protein antibiotic pyocin S5 kills Pseudomonas aeruginosa

Antimicrobial resistance is a deadly threat that is on the rise globally. Failure of small molecule antibiotic drug discovery programs and an increasing understanding of the dangers of antibiotic-induced dysbiosis of the microbiome have led to interest in bacteriocins as narrow-spectrum antibiotics. Pyocin S5 (PyoS5), a protein antibiotic against Pseudomonas aeruginosa, is the most potent colicin-like bacteriocin known but its structure and molecular mechanism remain poorly understood. This thesis presents the crystal structure of PyoS5, an elongated molecule with three structured domains and an unresolved N-terminal region, which enabled the functional, biochemical and biophysical characterization of this molecule. With its central domain, PyoS5 binds to common polysaccharide antigen (CPA), a lipopolysaccharide (LPS) antigen which acts as a receptor and accumulates the antibiotic on the cell surface. This is followed by binding to the outer membrane protein FptA, a TonB-dependent transporter (TBDT), by the N-terminal domain. A chimeric protein of Escherichia coli TonB and P. aeruginosa TonB1 allowed us to reconstruct the PyoS5 import process in E. coli, an approach that revealed that FptA acts as the translocator and that TonB1 energizes the import process by directly interacting with the N-terminal region of PyoS5. This import process and the structure of PyoS5 show strong similarity with those of PyoS2, which suggests that they are common to several pyocins targeting different TBDTs and delivering different cytotoxic domains into P. aeruginosa.

Keywords: membrane
transport
pyocin
Advisor: Kleanthous, C