VictorJuiz/thesis huggingface dataset:
Image-assisted surgical planning in gynaecological oncology

Major barriers to achieving progress in gynaecological cancer management are limitations in ovarian cancer treatment and morbidity related to lymphadenectomy in early stage cervical, vulval and endometrial cancers. The main morbidity of treatments for early endometrial, cervical and vulval cancers is surgery. Currently, all patients with high-­‐grade endometrial cancers, cervical cancers and squamous cell cancers of the vulva receive a complete regional lymphadenectomy. Complete lymphadenectomy causes significant morbidity, affecting the long-­‐term quality of life for these patients. There has been an emphasis on sentinel node biopsy to eliminate these morbidities, and some cancer centres already provide sentinel lymph node biopsy using radioactive isotopes, without compromising patient survival. Our study mainly focuses on a novel imaging technique using near infrared (NIR) with compatible dyes. We demonstrated the feasibility and efficacy of using intraoperative NIR for sentinel lymph node biopsy.
Advanced ovarian cancer management involves a combination of surgery and chemotherapy. The aim of surgery is to remove all visible disease before commencing chemotherapy or mid-­‐way during chemotherapy. Limitations to radical surgery are the unpredictability of radicality from available imaging modalities and patient morbidity. Limitations to chemotherapy are the limited response or resistance, mainly due to tumour heterogeneity. Our ovarian cancer pilot study aims to explore methods that could overcome the limitations of surgical planning prior to radical surgery and to identify tumour resistance in specific tumour sites by tracking the tumours during chemotherapy.

Advisor: Ahmed, A
‘Fixed fate, free will’: fate, natural law, necessity, providence, and classical epic narrative in Paradise Lost

The present thesis considers the allusive and narrative function of fate and its associated concepts of providence, free will, necessity, and natural law in Paradise Lost. It argues that the narrative function of these concepts is shaped by Milton's allusions to classical epic, and assesses their impact on the Christian theology of the poem. It identifies unnoted allusions to well-known epic models (Homer, Vergil, Lucan), and examines how Lucretius’ account of natural laws and post-Vergilian representations of epic aftermath influence Milton's own depiction of transgression and its aftermath in Paradise Lost.
Chapter 1 considers Satan and other fallen angels' definition of fate as a materialist alternative for the personal rule of the Father. It traces several allusions to fate in cosmological and ethical settings, in Lucretius, Vergil, Lucan, and Statius, and analyses how these allusions interact with the Hesiodic mythical material in the opening books of Milton’s epic.
Chapter 2 focuses on a pattern of previously unnoted allusions to Lucretius' De Rerum Natura in the narrative of the Fall, culminating in Book 9. It argues that in his temptation of Eve, Milton’s Satan subverts Lucretian teachings about the boundaries governing the physical universe as he persuades Eve to transgress her natural state in Eden.
Chapter 3 discusses the appearance of the Father in an allusive epic council scene in Book 3. In the dialogue between Father and Son, I suggest, Milton evokes negotiations between the Homeric and Vergilian deities, depicting his God as surpassing his pagan epic counterparts who can only delay the fate of mortals, but not change them.
Chapter 4 suggests that Milton’s depiction of the aftermath of the Fall is indebted to post-Vergilian epic narratives of 'aftermath'. The final Books of Paradise Lost and the portrayal of Adam and Eve's moral freedom as they leave paradise, with providence their guide, should be read, I posit, against the backdrop of scenes and imagery from Lucan’s Bellum Civile and Statius' Thebaid.

Keywords: Virgil – literary criticism
Early Modern Materialism
Statius – literary criticism
Fate and Providence in Epic
Lucretius – literary criticism
Homer – literary criticism
Lucan – literary criticism
Milton, Paradise Lost
Advisor: Harrison, S
Burrow, C
Generalized geometry of type Bn

Generalized geometry of type Bn is the study of geometric structures in T+T&ast;+1, the sum of the tangent and cotangent bundles of a manifold and a trivial rank 1 bundle. The symmetries of this theory include, apart from B-fields, the novel A-fields. The relation between Bn-geometry and usual generalized geometry is stated via generalized reduction.
We show that it is possible to twist T+T&ast;+1 by choosing a closed 2-form F and a 3-form H such that dH+F2=0. This motivates the definition of an odd exact Courant algebroid. When twisting, the differential on forms gets twisted by d+Fτ+H. We compute the cohomology of this differential, give some examples, and state its relation with T-duality when F is integral.
We define Bn-generalized complex structures (Bn-gcs), which exist both in even and odd dimensional manifolds. We show that complex, symplectic, cosymplectic and normal almost contact structures are examples of Bn-gcs. A Bn-gcs is equivalent to a decomposition (T+T&ast;+1)&Copf;= L + L̄ + U. We show that there is a differential operator on the exterior bundle of L+U, which turns L+U into a Lie algebroid by considering the derived bracket. We state and prove the Maurer-Cartan equation for a Bn-gcs.
We then work on surfaces. By the irreducibility of the spinor representations for signature (n+1,n), there is no distinction between even and odd Bn-gcs, so the type change phenomenon already occurs on surfaces. We deal with normal forms and L+U-cohomology.
We finish by defining G22-structures on 3-manifolds, a structure with no analogue in usual generalized geometry. We prove an analogue of the Moser argument and describe the cone of G22-structures in cohomology.

Keywords: twisted cohomology
generalized geometry
complex geometry
deformation theory
generalized complex geometry
Lie algebroid
almost contact geometry
G2(2)-structure
3-manifold
Advisor: Hitchin, N
State responsibility for omissions: establishing a breach of the full protection and security obligation by omissions

The full protection and security obligation traditionally requires a State to exercise due diligence to prevent physical damage from being inflicted on foreign investments within its territory, and to provide a means of redress for aggrieved foreign investors. Recently, tribunals have expanded this application of the obligation such that States are obliged to exercise due diligence to afford legal or regulatory protection to foreign investments.
Establishing a breach of the obligation involves establishing a State’s responsibility for its omissions. The law of State responsibility has nuances in respect of establishing a breach of non-absolute positive obligations, such as this one. Evidence of the State's knowledge of the need to act, and of its capacity to act, provide the basis on which a breach of the obligation may be established. Causation is also an element of the proof of a breach, and is to be established by reference to an adequate counter-factual. The standard to which one must establish a breach is contested – as between an objective and subjective standard, or a hybrid – albeit an objective standard of due diligence is preferable.
In this context, recent tribunals have fashioned diagnostics for determining a breach of the obligation which invoke concepts of legitimate expectations, and reasonableness and rationality. Using these diagnostics means that the objective standard of proof is satisfied when an investor’s legitimate expectations are frustrated by the conduct of the State, or when the State fails to act reasonably and in order to achieve rational public policy goals. These diagnostics offer a useful and workable development in the articulation of the standard of proof in relation to a breach of the full protection and security obligation.

Advisor: Berman, F
Essays in empirical and theoretical labor market models

This DPhil thesis is a collection of three theoretical and empirical papers studying labor markets in several advanced economies. Two chapters examine the relationship between the banking sector and the labor market in the US and the UK, while one evaluates a policy that has been proposed to help labor markets in the Euro Area adjust to economic shocks. In the first chapter, I develop a New Keynesian DSGE model that integrates a banking sector subject to moral hazard with a standard random search model of the labor market. I estimate the model using US data and study the role of the banking sector in determining labor market fluctuations. In the second chapter, I estimate a structural VAR model of the UK and US economies and identify bank lending shocks using a mix of sign and short-run exclusion restrictions. Consistent with the predictions of the DSGE model, an expansionary loan supply shock decreases job-destruction and increases job-creation, reducing the unemployment rate persistently. Bank lending shocks are also important drivers of labor market fluctuations, particularly during the Great Recession. Lastly, in the third chapter, I calibrate to the Euro Area a currency union DSGE model to evaluate the aggregate properties of European Unemployment Insurance (EUI). I find that EUI cannot contemporaneously stabilize the monetary union and achieve convergence in regional unemployment and inflation rates.

Keywords: Labor market model
Unemployment insurance
Banking models
DSGE
Financial frictions
SVAR
Advisor: Wren-Lewis, S
Zanetti, F
Interactions in complex traits

The availability of cheap genotyping technologies has enabled to collection of very large samples with both genetic and phenotypic information, enabling the interrogation of the genetic architecture of complex traits in humans and other organisms. The role of interactions between genetic variants and between genetic variants and environmental factors in complex traits is not well characterised, especially in humans. This is in part due to a lack of theory and methods designed for powerful investigation of interactions in complex traits in large-scale datasets. This thesis develops both theory and methods relating to interactions between genetic variants and between genetic and environmental factors, complemented by empirical analyses aimed at discovering the influence of interactions on complex traits. The effect of genetic variation on trait variation can be decomposed into components reflecting interactions involving different numbers of genetic variants. The first part of this thesis generalises classical theory on the decomposition of the genetic variance into components arising from different types of interaction to finite populations, where the influence of interactions is more easily detected. The theory is applied to determine the proportion of growth variance from pairwise and third and higher order interactions in a yeast cross. The subsequent parts of the thesis are more directly concerned with interactions between genetic variants and environmental factors. It is first demonstrated that multiple lifestyle factors modify the effect of variants in the FTO gene on body mass index (BMI). This motivates the development of the heteroskedastic linear mixed model (HLMM), which exploits changes in variability with genotype to aid discovery of genetic variants involved in interactions. An efficient algorithm for application of the HLMM to large scale datasets is developed and applied to discover genetic variants likely to be involved in interactions on BMI.

Advisor: Donnelly, P
A high-fidelity microwave driven two-qubit quantum logic gate in 43Ca+

Quantum computers offer great potential for significant speedup in executing certain algorithms compared to their classical counterparts. One of the most promising physical systems in which implementing such a device seems viable are trapped atomic ions. All of the fundamental operations needed for quantum information processing have already been experimentally demonstrated in trapped ion systems. Today, the remaining two obstacles are to improve the fidelities of these operations up to the point where quantum error correction techniques can be successfully applied, as well as to scale up the present systems to a higher number of quantum bits (qubits).
This thesis addresses both issues. On the one hand, it decribes the experimental implementation of a high-fidelity two-qubit quantum logic gate, which is the most technically demanding fundamental operation to realise in practice. On the other hand, the presented work is carried out in a microfabricated surface ion trap – an architecture that holds the promise of scalability.
The gate is applied directly to hyperfine "atomic clock" qubits in 43Ca+ ions using the near-field microwave magnetic field gradient produced by an integrated trap electrode. To protect the gate against fluctuating energy shifts of the qubit states, as well as to avoid the need to null the microwave field at the position of the ions, a dynamically decoupled Mølmer-Sørensen scheme is employed. After accounting for state preparation and measurement errors, the achieved gate fidelity is 99.7(1)%. In previous work, the same apparatus has been used to demonstrate coherence times of T&ast;2 ≈ 50 s and all single-qubit operations with fidelity > 99.95%.
To gain access to the "atomic clock" qubit transition in 43Ca+, a static magnetic field of 146G is applied. The resulting energy level Zeeman-structure is spread over many times the linewidth of the atomic transition used for Doppler cooling. This thesis presents a simple and robust method for Doppler cooling and obtaining high fluorescence from this qubit in spite of the complicated level structure. A temperature of 0.3mK, slightly below the Doppler limit, is reached.

Keywords: two-qubit gate
Advisor: Lucas, D
Ecotoxicology of silver nanoparticles to the soil nematode Caenorhabditis elegans: From molecular mechanisms to population consequences.

As the number of applications for engineered nanoparticles (ENPs) is increasing, so inevitably is the rate of their release into the environment. The novel properties (size, reactivity) that make their use and the development of applications appealing are also the basis for concerns about their environmental risks. Here the soil nematode Caenorhabditis elegans was used to assess the toxicity of various silver nanoparticle types with respect to gene expression, individual life history traits and population sensitivity. Exposures were carried out reflecting different environmentally relevant conditions that affected ENP fate and bioavailabilty. Characterisation of ENP fate in the media showed that while agglomeration/aggregation and dissolution processes occurred regardless of ENP type and exposure medium, their properties did alter the extent and dynamics of these processes. The toxicity of different Ag-ENPs and ionic silver was investigated and compared. Concentration-dependent decreases in reproduction were found for all silver forms with Ag+ being the most toxic by mass throughout. The effects of environmentally-relevant exposure media on ENP fate and reproductive toxicity to C. elegans was assessed, first by conducting tests in artificial media with varied composition, and second by using pore waters from soils with different properties. In both cases media pH had the greatest impact on observed toxicity. Multigenerational exposure to pristine and aged (sulfidised) Ag-ENPs revealed significant increases in sensitivity towards ionic and pristine Ag-ENP exposures in the second offspring generation (a novel finding), from which populations did not recover; aged ENPs did not induce similar increased sensitivity. Finally, using microarray analysis clear differences in gene expression after exposure to size and surface property-variant ENPs were found, yet changes in neurological functions were identified as the main underlying mode of toxic action regardless of ENP properties. This PhD thus provides a comprehensive assessment of Ag-ENP exposure, mechanisms of toxicity and long-term effects in a soil dwelling species.

Advisor: Crossley, A
Grovenor, C
Svendsen, C
Spurgeon, D
Modelling of amyotrophic lateral sclerosis (ALS) using induced pluripotent stem cells (iPSC)

The hexanucleotide repeat expansion (HRE) mutation within C9orf72 gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Several hypotheses have been proposed for how the mutation contributes to pathogenicity, including the loss of C9orf72 gene function, RNA-mediate toxicity and the formation of toxic dipeptides by repeat-associated non-ATG (RAN) translation. Patient-specific iPSCs provide a promising tool for the study of the cellular and molecular mechanisms of human diseases in relevant cell types and discovering potential therapies. The CRISPR (clustered regularly interspaced short palindromic repeats)-Cas9-mediated homology directed repair (HDR) system represents an attractive approach for disease modelling and development of therapeutic strategies. In this thesis, iPSCs derived from ALS/FTD patient carrying the HRE mutation were generated and subsequently gene edited to remove a massive repeat expansion from the patient cells and replace it with the wild-type size of the repeats using HDR and a plasmid donor template. The successful genotypic correction of the mutation resulted in the normalization of the C9orf72 gene promoter methylation level and the gene variants RNA expression level. Removal of the mutation also resulted in abolition of sense and antisense RNA foci formation and reduction of DPRs accumulation. Furthermore, the repeat size correction also rescued the susceptibility of cells to Glutamate excitotoxicity, decreased the apoptotic cell death and stress granules formation under the baseline and stress conditions. This work provides a proof-of-principle that removal of the HRE can rescue ALS disease phenotypes and provides an evidence that HRE mutation is an attractive target for therapeutic strategies and drug screening, to block the underlying disease mechanisms.

Advisor: Talbot, K
Cowely, S
Investigations into transcription and transcripts in Saccharomyces cerevisiae

Transcription of the Saccharomyces cerevisiae genome by RNA polymerase II (Pol II) is pervasive, occurring on the sense and antisense strands of protein-coding genes and at intergenic regions. Factors associate with Pol II at particular positions along transcribed regions (transcription units (TUs)) with functions including facilitating the transition of Pol II through chromatin, controlling termination and processing the nascent transcript. By developing a new technique, these associations were mapped strand-specifically with nucleotide resolution. This revealed increased transitions in the binding of factors along TUs, periodic binding as Pol II transcribes through nucleosomes and differential binding of particular factors to particular types of TU. These associations are regulated to influence the stability and subcellular location of the transcripts produced. Analysis of transcription levels upon a change in conditions showed widespread and rapid changes resulting from changes in the proportion of cells in particular phases of the yeast metabolic cycle. At individual loci, clustered TUs showed reciprocal changes in transcription. Overlap between coding and non-coding TUs on both strands was shown to regulate these changes, repressing out of phase transcription. While the process of non-coding transcription is generally thought to be the regulatory agent, a role for non-coding transcripts should not be overlooked. Non-coding RNAs were shown to be able to bind double-stranded DNA sequence-specifically at several locations providing a mechanism by which these RNAs could interact with chromatin and mediate a function.
Robert Jenson's Trinitarian reconstitution of metaphysics

This thesis provides a critical examination of Robert Jenson’s doctrine of the Trinity, and the ways in which Jenson’s development of this doctrine corrects central aspects of contemporary metaphysics. Jenson's doctrine of the Trinity develops from his belief in the significance of the narrative form of Scripture, and the way in which the Christian Gospel addresses human religiosity. In order to explain this development, the thesis addresses some topics not addressed in scholarship on Jenson, especially his understanding of theological language and his approach to religious epistemology. It also describes the ways in which Jenson's theological project coheres with the task and method of contemporary metaphysics.
After describing Jenson's doctrine of the Trinity, the thesis moves on to address substantial critiques from George Hunsinger, David Bentley Hart, and Oliver Crisp. Hunsinger critiques Jenson on the ground of orthodoxy. He claims that Jenson’s views commit him to a number of heresies, both ancient and modern. David Bentley Hart also critiques Jenson for his perceived unorthodoxy, arguing that Jenson makes the world necessary for God, and makes God responsible for evil in a way which is at odds with the Christian faith. Oliver Crisp critiques Jenson's metaphysics on the grounds of coherence. The thesis provides responses to all of these critiques.
Following these critiques, the thesis describes the ways in which Jenson’s Trinitarianism reconstitutes certain central aspects of contemporary metaphysics, especially in the philosophy of time and fundamental metaphysics. Jenson argues on Trinitarian grounds that Christians ought to hold something akin to a moving spotlight view of time. He also argues that Christians ought to deny the category of substance and hold 'event' to be the primary category of metaphysics.
The thesis also highlights several weaknesses in Jenson's thought: he has no clear epistemology, his response to the problem of evil is inconsistent, and his work on 'being' is misdirected. None of these weaknesses are found to be fatal to Jenson's project, and the thesis offers suggestions for how each in turn could be corrected.

Keywords: Metaphysics
Robert Jenson
Trinity
Time
Ontology
Advisor: Zachhuber, J
Wood, W
New approaches to the investigation of the interactions between enhancers and promoters during haemopoiesis

Next generation sequencing based methods allow us to identify active genes and potential regulatory elements rapidly across the genome, but an outstanding challenge is to unravel which regulatory elements control which genes. This is problematic because regulatory elements control genes over huge distances (over 1 million base pairs) and they have an unpredictable distribution around the genes they influence. In order to enhance transcription the protein complexes at distal regulatory elements make physical contact with the promoter. These interactions can be detected using Chromosome Conformation Capture (3C) technology and the position of regulatory elements can be deduced from these data. However, these methods are either low throughput or low resolution and they are prone to bias. In this 3C techniques were specifically developed to determine the interactions between regulatory elements and gene promoters promoter. The focus has been the development of Next Generation Capture-C, which allows many genetic loci and samples to be analysed simultaneously, with greater sensitivity and accuracy than has previously been possible. High resolution data can be produced from as few as 100,000 cells, and single-nucleotide polymorphisms can be used to generate allele-specific tracks. Nanostring technology has also been developed for analysis of 3C libraries, as this allows interaction profiles to be determined without PCR or sequencing bias. The Nanostring data show remarkable correlation with the interaction profiles generated by NG Capture-C.

Keywords: Chromatin Conformation Capture
Advisor: Higgs, D
Hughes, J