VictorJuiz/thesis huggingface dataset:
The role of Topoisomerase II in replication in mammalian cells

Topoisomerase 2α (Topo2α) is an essential protein with DNA decatenating enzymatic properties, indispensable for chromosome decatenation and segregation. It is a target for a plethora of antitumour drugs and Topo2α protein levels have been associated with the success of treatment, but also drug resistance and secondary malignancies. Although unique in its ability to resolve catenated chromosomes, the role of Topo2α in other steps of DNA metabolism, such as DNA replication elongation and termination have been elusive. A thorough understanding of the role of Topo2α in the cell will not only allow for increased insight into the mechanisms it is involved in, but it will also shed light on proteins and pathways that can act as back-up in its absence, and therefore hopefully expand the basis on which to improve treatment options.
Through a synthetic lethal interaction (SLI) screen with an siRNA library targeting 200 DNA repair and signalling genes, Topo2α emerged as being synthetic lethal to Werner protein (WRN), a RecQ helicase involved in maintaining genome integrity mainly in S phase, and the loss of which leads to Werner Syndrome (WS), a segmental progeroid syndrome. The screen was performed in WRN deficient cells, with the initial aim to find proteins that act to buffer against loss of viability, which is the central idea in the concept of synthetic lethality in the absence of WRN. The screen revealed an SLI between WRN and Topo2α and although we were unable to fully validate this, it spurred the question of Topo2α’s role in DNA replication.
The findings in this thesis suggest that Topo2α is not required for DNA elongation and timely completion of S phase, and that simultaneous loss of the closely related isoform Topo2β does not affect replication, suggesting that these proteins do not act in parallel back-up pathways during replication. Interestingly, cells accumulate in the polyploid fraction after both depletion and inhibition of Topo2α, albeit with different kinetics. The mechanistic basis of this phenotype remains to be understood through further research, but it is highly interesting as aneuplidity and polyploidy are implicated in the initial stages of tumour development.

Keywords: DNA combing
DNA replication
siRNA screening
Topoisomerase
synthetic lethality
DNA repair
Werner Syndrome
Advisor: Helleday, T
Generation and application of semantic networks from plain text and Wikipedia

Natural Language Processing systems crucially depend on the availability of lexical and conceptual knowledge representations. They need to be able to disambiguate word senses and detect synonyms. In order to draw inferences, they require access to hierarchical relations between concepts (dog isAn animal) as well as non-hierarchical ones (gasoline fuels car). Knowledge resources such as lexical databases, semantic networks and ontologies explicitly encode such conceptual knowledge. However, traditionally, these have been manually created, which is expensive and time consuming for large re- sources, and cannot provide adequate coverage in specialised domains.
In order to alleviate this acquisition bottleneck, statistical methods have been created to acquire lexical and conceptual knowledge automatically from text. In particular, unsupervised techniques have the advantage that they can be easily adapted to any domain, given some corpus on the topic. However, due to sparseness issues, they often require very large corpora to achieve high quality results. The spectrum of resources and statistical methods has a crucial gap in situations when manually cre- ated resources do not provide the necessary coverage and only limited corpora are available. This is the case for real-world domain applications such as an NLP system for processing technical information based on a limited amount of company documentation.
We provide a large-scale demonstration that this gap can be filled through the use of automatically generated networks. The corpus is automatically transformed into a network representing the terms or concepts which occur in the text and their relations, based entirely on linguistic tools. The net- works structurally lie in between the unstructured corpus and the highly structured manually created resources. We show that they can be useful in situations for which neither existing approach is ap- plicable. In contrast to manually created resources, our networks can be generated quickly and on demand. Conversely, they make it possible to achieve higher quality representations from less text than corpus-based methods, relieving the requirement of very large scale corpora.
We devise scaleable frameworks for building networks from plain text and Wikipedia with varying levels of expressiveness. This work creates concrete networks from the entire British National Corpus covering 1.2m terms and 21m relations and a Wikipedia network covering 2.7m concepts. We develop a network-based semantic space model and evaluate it on the task of measuring semantic relatedness. In addition, noun compound paraphrasing is tackled to demonstrate the quality of the indirect paths in the network for concept relation description. On both evaluations we achieve results competitive to the state of the art. In particular, our network-based methods outperform corpus-based methods, demonstrating the gain created by leveraging the network structure.

Keywords: natural lanuage processing
semantic networks
Advisor: Pulman, S
Studies on Aedes polynesiensis introgression and ecology to facilitate lymphatic filariasis control

The mosquito Aedes polynesiensis, a member of the Aedes scutellaris complex, is the main vector in the South Pacific region of the Wuchereria bancrofti parasite, the causative agent of lymphatic filariasis (LF), and is also a major nuisance biter. Decades of Mass Drug treatment (MDA) have not been successful in elimination LF. Two non-vector species in the Ae. scutellaris complex were introgressed with Ae. polynesiensis to attempt to obtain lines that would produce cytoplasmic incompatibility (CI) with wild populations and / or LF-refractoriness. Despite selection of progeny from Brugia-challenged, non-infective females at each backcross, no refractory line was acquired. However, three lines from crosses between aposymbiotic Ae. polynesiensis and Ae. riversi displayed CI and male mating competiveness suitable for the purpose of population suppression using the incompatible insect technique (IIT). A population study was conducted of potential release sites and the evaluation of monitoring tools for Ae. polynesiensis on Moorea and Tetiaroa, French Polynesia. There was no evidence of active migration between selected islets on the atoll of Tetiaroa, suggesting it is a suitable site for field releases of CI males. The BioGents Sentinel trap was shown to be an efficient and convenient trap suitable for Ae. polynesiensis monitoring. The effects of temperature and larval density on life-table parameters relevant to IIT were examined, including: larval survivorship, developmental time to pupation, male to female ratio, male pupae yield, male size and adult male survival. These findings were used to design and conduct a 14-week field experiment testing CI male strain against an isolated population, using optimized rearing conditions. Approximately 8000 males were released weekly on motu Onetahi, Tetiaroa atoll. Significant sterility was induced by Wolbachia in the targeted female population, supporting the development and scale-up of this approach toward Ae. polynesiensis nuisance and LF transmission reduction.

Keywords: lymphatic filariasis
sterile insect technique
Aedes polynesiensis
Wolbachia
Advisor: Sinkins, S
Compensation claims against trustees

The thesis examines the claims that may be brought against express trustees for pecuniary compensation. It contends that a difference of principle divides this conventional category in two. Some compensation claims complain that the trustee has breached one of his duties and seek to charge him with reparation for whatever ensuing loss has been suffered by the beneficial interests. These claims resemble claims for damages founded upon a tort or breach of contract. Other compensation claims overlook whatever breach there may have been and demand that the trustee account and perform the trusts, in money where this cannot be done in specie. This second type of claim resembles a claim for the specific performance of a contract, bearing in mind that specific performance may be given with compensation where the defendant cannot deliver what he has promised. The claims are cumulative subject to the principle of full satisfaction.

Advisor: Jeffrey Hackney, P
Discovery and measurement of the Higgs boson in the WW decay channel

In the Standard Model of particle physics, the non-zero masses of the W and Z bosons and the fermions are generated through interactions with the Higgs field, excitations of which correspond to Higgs bosons. Thus, the experimental discovery of the Higgs boson is of prime importance to physics, and would confirm our understanding of fundamental mass generation.
This thesis describes a search for the gg → H → WW → lνlν process of Higgs boson production and decay. It uses the LHC Run I dataset of pp collisions recorded by the ATLAS detector, which corresponds to an integrated luminosity of 4.5 fb−1 at √ s = 7 TeV and 20.3 fb−1 at √ s = 8 TeV. An excess of events is observed with a significance of 4.8 standard deviations, which is consistent with Higgs boson production. The significance is extended to 6.1 standard deviations when the vector boson fusion production process is included. The measured signal strength is 1.11+0.23-0.21 at mH = 125 GeV. A cross section measurement of WW production, a major background to this search, is also presented using the √ s = 7 TeV dataset only.

Keywords: Higgs boson
ATLAS
LHC
Advisor: Hays, C
Disenfranchisement of convicted adult citizens: comparative and international human rights perspectives

This thesis analyses the appropriateness of disenfranchising convicted adult citizens from comparative and international human rights perspectives.
Chapter One explores the transition from direct democracy to representative government, and the subsequent increased importance of elections. It highlights the paradigm shift that the perception of voting has undergone, from being seen as a privilege, granted to a handful of society members, to being viewed as an entitlement. Today, electoral systems are commonly based on universal suffrage, and voting eligibility is normally qualified by (only) two criteria: community membership and competence. It is suggested that these criteria should be used for scrutinising convicts’ disenfranchisement.
Chapter Two traces the transformation that the treatment of convicts underwent, with notions of forfeiture of rights and ‘civil death’ gradually giving way to ideas of 'residual liberty' and of convicts as rights-holders. Subsequently, regulatory and penal justifications for convicts' disenfranchisement are assessed. The analysis concludes that disenfranchisement should be classified as a form of punishment, and that, due to its adverse effects on individuals as well as collectives disenfranchisement should cease to be imposed.
Chapter Three offers comparative perspectives on current challenges to disenfranchisement legislation. It examines American disenfranchisement jurisprudence alongside recent judgments from Canada, South Africa, the European Court of Human Rights and Australia. It is concluded that the non-American judgments exhibit an identifiable global trend towards enfranchising (some) convicts which can be partially attributed to a transnational judicial discourse.
Chapter Four examines the human rights treaty regime's perspective. Interpreting Article 25 of the International Covenant on Civil and Political Rights which guarantees the right-to-vote, it is posited that the provision does not proscribe disenfranchisement as such. Rather, disenfranchisement is subjected to balancing/proportionality analysis. Building on Chapter Two's normative contentions, and on the notion that voting eligibility constitutes the essence of the right-to-vote, the thesis advocates the adoption of an optional protocol to the ICCPR proscribing disenfranchisement. It is submitted that the facilitative nature of the right-to-vote makes it less vulnerable to cultural relativity, deference and margin of appreciation objections. Analogies are drawn between the proposed protocol and the Optional Protocol to the ICCPR Aiming at the Abolition of the Death Penalty.

Keywords: conviction
democracy
right to vote
elections
punishment
European court of human rights
international human rights law
prisoners rights
disenfranchisement
suffrage
Advisor: McCrudden, C
Arms control policy of the People's Republic of China, 1949-1978

This study investigates how the PRC, during the three decades since its establishment, has responded to international politics involving arms control and disarmament (ACD) issues, and explores the essence of China's approach to concepts of arms control and disarmament. The central finding is that, despite its seeming relaxation of hostility towards international ACD activities, and the more active and flexible part it has played in them at the UN since the mid-1970s, China remains unconvinced of the value of these activities. This does not make it dangerous, irrational or immature.
Chapters Two to Five provide a comprehensive account of the history of Chinese ACD policy between 1949 and 1978. Each chapter represents a distinctive period of Chinese arms control policy. Although more interested in the banning of the use, rather than the possession, of atomic weapons, the PRC behaved at first as an uncritical disciple of Soviet ACD positions (Chapter Two). During the second period (Chapter Three), China became increasingly uneasy about international ACD efforts and began to deviate from the Soviet stance. Moscow's denial of concrete assistance to China's nuclear weapons development, and the conclusion of the Partial Test Ban Treaty, eventually led the PRC into a period (Chapter Four) of open hostility towards nearly all international ACD initiatives. Then, in 1964, China's first nuclear test likewise radically changed its outlook on ACD matters. The final period (Chapter Five) examines its record at the UN in this regard, showing how the PRC was persuaded to commit itself to the Tlatelolco Treaty and to the 1978 UN Special Session on Disarmament.
In conclusion, however, there is no evidence to suggest that the PRC has been committed to the concept of a disarmament process through arms control which both the US and the USSR, in their very different ways, have accepted. China has participated in international ACD negotiations while not really believing in their objectives, based as these are on a permanency of two superpowers. It is to be hoped that China's increasing involvement in the UN disarmament negotiation machinery will feed back into PRC policy-making and lead to a more positive and more willing participation in these ACD negotiations.
Investigating aerosol-cloud interactions

Microphysical and dynamical interactions between aerosols and clouds are associated with some of the largest uncertainties in projections of future climate. Many possible aerosol effects on clouds have been suggested, but large uncertainties remain. In order to improve model projections of future climate, it is essential that we improve our quantitative understanding of anthropogenic aerosol effects. Several studies investigating interactions between satellite-observed aerosol and cloud properties have been published in recent years. However, the observed relationships are not necessarily due to aerosol effects on clouds. They may be due to cloud and precipitation effects on aerosol, meteorological covariation, observational data errors or methodological errors. An analysis of methodological errors arising through climatological spatial gradients is performed. For region sizes larger than 4°×4°, commonly used in the literature, spurious spatial variations in retrieved cloud and aerosol properties are found to introduce widespread significant errors to calculations of aerosol-cloud relationships. Small scale analysis prior to error-weighted aggregation to larger region sizes is recommended. Appropriate ways of quantifying relationships between aerosol optical depth (τ) and cloud properties are considered, and results are presented for three satellite datasets. There is much disagreement in observed relationships between τ and liquid cloud droplet number concentration and between τ and liquid cloud droplet effective radius, particularly over land. However, all three satellite datasets are in agreement about strong positive relationships between τ and cloud top height and between τ and cloud fraction (f_c). Using reanalysis τ data, which are less affected by retrieval artifacts, it is suggested that a large part of the observed f_c-τ signal may be due to cloud contamination of τ. General circulation model simulations further demonstrate that positive f_c-τ relationships may primarily arise due to covariation with relative humidity, and that negative f_c-τ relationships may arise due to scavenging of aerosol by precipitation. A new method of investigating the contribution of meteorological covariation to the observed relationships is introduced. Extratropical cyclone storm-centric composites of retrieved aerosol and cloud properties are investigated. A storm-centric description of the synoptics is found to be capable of explaining spurious f_c-τ relationships, although the spurious relationships explained are considerably smaller than observed relationships.

Keywords: aerosols
atmospheric
climate
physics
clouds
Advisor: Stier, P
Embedding an object calculus in the unifying theories of programming

Hoare and He's Unifying Theories of Programming (UTP) provides a rich model of programs as relational predicates. This theory is intended to provide a single framework in which any programming paradigms, languages, and features, can be modelled, compared and contrasted. The UTP already has models for several programming formalisms, such as imperative programming, higher-order programming (e.g. programing with procedures), several styles of concurrent programming (or reactive systems), class-based object-orientation, and transaction processing. We believe that the UTP ought to be able to represent all significant computer programming language formalisms, in order for it to be considered a unifying theory. One gap in the UTP work is that of object-based object-orientation, such as that presented in Abadi and Cardelli's untyped object calculi (sigma-calculi). These sigma-calculi provide a prominent formalism of object-based object-oriented (OO) programs, which models programs as objects. We address this gap within this dissertation by presenting an embedding of an Abadi--Cardelli-style object calculus in the UTP. More formally, the thesis that his dissertation argues is that it is possible to provide an object-based object rientation to the UTP, with value- and reference-based objects, and a fully abstract model of references. We have made three contributions to our area of study: first, to extend the UTP with a notion of object-based object orientation, in contrast with the existing class-based models; second, to provide an alternative model of pointers (references) for the UTP that supports both value-based compound values (e.g. objects) and references (pointers), in contrast to existing UTP models with pointers that have reference-based compound values; and third, to model an Abadi-Cardelli notion of an object in the UTP, and thus demonstrate that it can unify this style of object formalism.

Keywords: object references
predicative programming
object orientation
pointers
unifying theories of programming
object calculus
Advisor: Gibbons, J
Silica-on-silicon waveguide circuits and superconducting detectors for integrated quantum information processing

Building complex quantum systems has the potential to reveal phenomena that cannot be studied using classical simulation. Photonics has proven to be an effective test-bed for the investigation of such quantum-enhanced technologies, however, the proliferation of bulk optical components is unlikely to be a scalable route towards building more complex devices. Instead, the miniaturisation, inherent phase stability and trivial alignment afforded by integrated photonic systems has been shown to be a promising alternative.
In the first half of this thesis, we describe experiments exploiting the quantum interference of three single photons on a reconfigurable integrated photonic chip. We develop a low-loss source of single photons and introduce a low-loss silica-on-silicon waveguide architecture which enables us to show the first genuine quantum interference of three single photons on an integrated platform. A loss-tolerant, element-wise characterisation scheme is developed along with a statistical test to verify that this multi-photon circuit behaves as expected. We then make use of this three-photon interference to detail the first proof-of-principle demonstration of a new intermediate model of quantum computation called boson sampling. Finally, we perform an on-chip demonstration of the quantum teleportation protocol where all key parts --- entanglement preparation, Bell-state analysis and quantum state tomography --- are performed on a reconfigurable photonic chip. The element-wise characterisation scheme developed earlier is shown to be critical to mitigate fabricated component errors. We develop a theoretical model to account for all sources of possible error in the circuit and find good agreement with the measured teleported state fidelities, which exceed the average teleportation fidelity possible with a classical device. We identify the elements of this error budget relevant to scaling and propose improvements to chip characterisation and fabrication in order to achieve high fidelity operation.
In the second half, we discuss the use of high efficiency superconducting transition edge sensors in enabling quantum experiments using more photons. We detail the installation and characterisation of these detectors in a new lab in Oxford. We achieve good photon number-resolution and high-efficiency operation. Work to integrate these detectors on the silica-on-silicon waveguide architecture is discussed and we detail the optical and thermal device modelling performed to optimise the on-chip detection efficiency. New, on-chip detectors, fabricated according to this design are shown to operate as expected and achieve high-efficiency and good energy resolution.

Keywords: photon detectors
quantum optics
integrated optics
Quantum information
quantum teleportation
quantum interference
Advisor: Walmsley, I