VictorJuiz/thesis huggingface dataset:
An approach to the synthesis of the cytochalasans

The cytochalasans, a group of biologically active secondary metabolites isolated from micro-organisms, are tricyclic compounds which comprise of a heavily oxygenated 11-, 13- or 14-membered ring trans -fused to a substituted 8-azabicyclo [4.3.0]nonane ring system.
One approach to the total synthesis of the cytochalasans involves the intramolecular Diels-Alder cyclization of a suitable 3-substituted- Δ3 - pyrrolin-2-one. As preliminary work, a synthetic route to 5̱S-1-acyl-5- benzyl-3-butyl- Δ3 -pyrrolin-2-ones was developed, starting from the known lactam, 5̱R-5-benzylpyrrolidin-2-one. However, although these dienophiles reacted stereospecifically with 2̱E,4̱E-hexadiene, the reaction conditions were harsh (200°, 30-50 h) and the sequence suffered from low overall yields.
The doubly activated dienophile, 5̱S-1-benzoyl-5-benzyl-3-(1-oxopropyl)- Δ3 -pyrrolin-2-one, on the other hand, was available via an expeditious route from the N -protected lactam, 5̱R-5-benzyl-1-(tert-butyldimethylsilyl)pyrrolidin- 2-one. Moreover, the dienophile reacted stereoselectively with 2̱E,4̱Ehexadiene under milder conditions (100°, 8 h) to give, after deprotection, 7-benzyl-2,5-dimethyl-1-(1-oxopropyl)-8-azabicyclo[ 4.3.0] non-3-en-9-one. The stereochemistry of the isoindolone adduct was shown to be the same as in naturally occurring cytochalasans. The overall yield from 5̱R-5-benzylpyrrolidin- 2-one after seven steps was 16%.
In comparative studies, the doubly activated dienophile 1-benzenesulphonyl- 3-(1-oxopropyl)- Δ3 -pyrrolin-2-one was prepared and its reactions with 2̱E,4̱E-hexadiene and cyclopentadiene were studied. Although the stereoselectivity was better than for the N-benzoylated pyrrolin-2-one, isolated yields of cycloadducts were inferior.
Thus,as a model for ah approach to the [13]cytochalasans, the dienedienophile, 5̱S ,12̱E,14̱E-1-benzoyl-5-benzyl-3-(1-oxohexadeca-12,14-dienyl)- Δ3 -pyrrolin-2-one, was prepared in 20% overall yield from 5̱R-5-benzylpyrrolidin- 2-one. Regio- and stereoselective cyclization was achieved under high pressure conditions (11-13 kbar) to give a tricyclic compound in 16-35% yield. The stereochemistry of the deprotected major adduct was shown to be that required for cytochalasan synthesis. Thus, the intramolecular Diels- Alder approach to cytochalasan synthesis using diene-lactams was validated.

Advisor: Thomas, E
Thomas, J
Monocyte profile and function in sarcoidosis

Sarcoidosis is a multisystem inflammatory disorder of unknown aetiology. The immune pathology is characterised by dysregulated T cell (TH1) activity, macrophage activation and granuloma formation, resulting in systemic inflammation, and organ dysfunction. I hypothesised that, as the systemic precursor to the macrophage, altered monocyte activity in sarcoidosis may contribute to the early immune pathology of the disease. In this thesis, I examined their phenotype, four key monocytic functions: cytokine production, suppression of T cell proliferation, phagocytosis and fusion (as a precursor to granulomagenesis); and their gene expression profile compared to monocytes from healthy controls.
My data show that the expanded monocyte compartment comprise a greater proportion of the inflammatory (CD14++CD16+) and patrolling (CD14+CD16++) subsets, increased TNFα and IL-12 and decreased IL-10 and IL-4 production in sarcoidosis compared with healthy controls. The IL-10 deficit renders the monocytes less able to regulate T cell proliferation or their own fusion to multinucleate giant cells, potentially contributing to T cell expansion and granuloma formation respectively. Additionally, sarcoidosis monocytes are less able to phagocytose inert material. I also showed that previously reported deficiency in invariant NKT cells and low serum vitamin D levels in sarcoidosis may be linked to reduced IL-10 production by monocytes. Vitamin D treatment in vitro restored most of these deficiencies and provides a potential therapeutic method for manipulating monocyte function and disease genesis in sarcoidosis.

Keywords: Monocytes
Interstitial lung disease
Respiratory medicine
Sarcoidosis
Advisor: Ho, L
McMichael, A
Studies on the synthesis of oxygen carriers

To mimic the properties of haemoglobin (Hb) and myoglobin (Mb) it has been found necessary to synthesise a five-coordinate ferrous porphyrin with a protecting structure over the sixth coordination site at iron.
This thesis describes approaches to the synthesis of such a compound where the protecting structure is the "capped" moiety and where the base which occupies the fifth coordination site is held in position by two covalent linkages to the porphyrin. The preparation of the target molecule involved the synthesis of a new "capped" porphyrin and a series of difuncticnalised pyridines. These were then successfully coupled under high dilution conditions to give the "capped/strapped" porphyrin. Metallation and reduction completed the synthesis.
The behaviour of the ferrous complex in the presence of dioxygen was investigated. High stability toward irreversible oxidation was found. In the presence of oxygen the ferrous complex had a half-life in excess of 40h at room temperature.

Advisor: Baldwin, J
Aspects of the class S superconformal index, and gauge/gravity duality in five/six dimensions

In the first part of this thesis, we discuss some aspects of the four-dimensional N = 2 superconformal index of theories of class S. We first consider a generalized index on S1 × S3/ℤr, and prove S-duality in a particular fugacity slice. We then go on to study the (round) superconformal index in the presence of surface defects. We develop a systematic prescription to compute surface defects labeled by arbitrary irreducible representations of the gauge group and subject those defects to various tests in several different limits. Each of these limits is interesting in its own right, and we go on to explore them in some depth.
In the second part of this thesis, we construct the gravity duals of large N supersymmetric gauge theories defined on squashed five-spheres with SU(3) × U(1) symmetry. The gravity duals are constructed in Euclidean Romans F(4) gauged supergravity in six- dimensions, and uplift to massive type IIA supergravity. We compute the partition function and Wilson loop in the large N limit of the gauge theory and compare them to their corresponding supergravity dual quantities. As expected from AdS/CFT, both sides agree perfectly. Based on these results, we conjecture a general formula for the partition function and Wilson loop on any five-sphere background, which for fixed gauge theory depends only on a certain supersymmetric Killing vector. We then go on to construct rigid supersymmetric gauge theories on more general Riemannian five-manifolds. We follow a holographic approach, realizing the manifold as the conformal boundary of the six-dimensional bulk supergravity solution. This leads to a systematic classification of five-dimensional supersymmetric backgrounds with gravity duals.

Keywords: High Energy Physics
Mathematical Physics
Advisor: Alday, L
Mitochondrial modulators of hypoxia-related pathways in tumours

The Lon protease is a mitochondrial matrix quality-control protease belonging to the family of AAA+ proteins (ATPases associated with many cellular activities). We had previously found Lon to be upregulated in lung tumours with a non-angiogenic phenotype in a microarray study comparing these to conventional angiogenic tumours. In this project I set out to investigate whether Lon had any role in modulating the hypoxic response of tumour cells. Using a novel monoclonal antibody against Lon, I found that upregulation of Lon was present in breast and lung tumours and that higher levels of Lon are correlated with shorter overall survival in breast cancer patients. Targeting Lon with siRNA and shRNA in tumour cell lines reduced the normoxic and hypoxic stabilisation of HIF-α subunits. This is mediated through a mechanism independent of the activity of HIF-prolyl hydroxylases and independent of any changes in mitochondrial transcription. I found that the pre-imported form of Lon could bind and chaperone VHL in the cytoplasm potentially modulating VHL activity. In cell lines and human tumours, I observed that the proline-hydroxylated form of HIF-1α is induced by hypoxia and the hydroxylated form of HIF-1α is associated with shorter overall survival in breast cancer patients. This observation supports the notion that higher levels of Lon is associated with poor survival by downregulating VHL leading to higher levels of hydroxylated HIF. Finally I show that targeting Lon in cell lines is able to inhibit growth in a cell-line dependent fashion and partially reverses the Warburg effect, increasing oxygen consumption and reducing lactate production. In conclusion, I have demonstrated the broad therapeutic potential of targeting the Lon protease in tumours and highlighted a mechanism of post-hydroxylation HIF-regulation that has not been previously recognised in VHL competent tumours.

Keywords: mitochondria
Warburg effect
Lon protease
breast cancer
HIF
hypoxia
tumour metabolism
mitochondrial unfolded proteins
angiogenesis
Proline hydroxylation
Advisor: Pezzella, F
Gatter, K
The reformed theology of Benjamin Keach (1640-1704)

Benjamin Keach, the most prolific Particular Baptist theologian of the seventeenth century, described himself as a defender of ‘Reformed Orthodoxy’. Despite this self-identification, modern scholarship has largely relegated Keach to a self-educated dissenting pastor whose major achievement could be found in his controversial support of hymn singing. Two recent dissertations have attempted to revise this view of Keach, but no scholarly work has yet attempted to wrestle holistically with Keach’s view of himself as a Reformed theologian. This work fills that void by reviewing Keach’s own understanding of the term ‘Reformed Orthodoxy’, reconstructing Keach’s connections both in the personal contacts available in dissenting London and Buckinghamshire and in the books at his disposal, examining the major aspects of his theology, and placing that theology within the spectrum of Reformed Orthodoxy. From the time of his entry onto the public theological stage, Keach quickly became identified with those with whom he networked intellectually. From his branding as a Fifth Monarchist to his identification first as a General Baptist and later as the most prominent Particular Baptist, those connections proved to be the most idiosyncratic characteristic of Keach’s theological pilgrimage. Those connections crossed the conventional lines of systematic theology and boundaries of religious sects, resulting in Keach’s theology crossing those same lines yet remaining Reformed in its major assertions. Following the organizational structure of Keach’s catechisms and confessions, this work proceeds by expounding and interrogating Keach’s major theological positions—his understanding of the Trinity including this doctrine’s foundational role in ecclesiology, the significance of the covenants, justification, and eschatology. Throughout this exposition, Keach’s theological lenses, shaped by his contacts and his independent, creative thought, become clear. Ultimately, Keach proves himself to be a capable Reformed theologian, able and willing to dialogue with the most influential theologians, yet consistently forging his own ground within Reformed Orthodoxy as a whole and more specifically Particular Baptist theology.

Keywords: Southwark
Church History
Particular Baptist
theology
Christianity
Baptist
Reformed Theology
Benjamin Keach
Advisor: Briggs, J
Hedging Strategies Under Temporary Market Impact


This thesis is concerned with the problem of hedging derivatives under temporary market impact. We are going to examine the problem of hedging derivatives in an optimal control setting similar to [14] and [10]. By considering specific combinations of volatility and liquidity specifications, we are able to obtain analytic solutions. Under the optimal control, the holdings in the stock exhibit a mean reverting behavior. While the reversion-speed is similar to the results in the literature, we are able to find a new characterization of the target portfolio as weighted average of future Δ-hedge portfolios. If the stock-price process is given by a Brownian motion, this characterization collapses to the Δ-hedge. In that case, the final hedging error is proportional to the variance of the Δ-hedge. Further, we extend the analysis by including drift using asymptotic expansions. We find that under the optimal control, the wealth process is mean-reverting towards the expectation of the derivative. The hedging portfolio adjusts more to the inclusion of drift if future hedging is less aggressive. The comparison with numerical solutions suggests that the approximations perform reasonably well.
An investigation into the relation between corporate governance and firm value in the U.K

The separation of ownership from control, which characterises the modern firm, necessitates monitoring and inducement mechanisms to ensure that managers maximise shareholder wealth. This study investigates the relation of firm value to these corporate governance mechanisms. The results of the analysis show that there is considerable interdependence between corporate governance and firm structure variables. Most importantly, it appears that the two principal governance mechanisms, managerial equity ownership and the board of directors, are optimally chosen. The methodology employed here suggests that previous work has not fully accounted for the comprehensive and simultaneous nature of the governance process.
Weaker evidence is obtained for directors' remuneration and outsider equity ownership. Directors' remuneration is substantially determined by the structure of the firm, and is not strongly related to the performance of the firm. In addition, it appears that large equity investors have different motivations and their presence within a firm's ownership structure may not always be associated with a monitoring function.
Semantics and refinement for a concurrent object oriented language

FOOPS is a concurrent object oriented specification language with an executable subset. In this thesis we propose an extension of FOOPS with features for specifying systems of distributed and autonomous objects. This extension supports most features of concurrent object oriented programming, including classes of objects with associated methods and attributes, object identity, dynamic object creation and deletion, overloading, polymorphism, inheritance with overriding, dynamic binding, concurrency, nondeterminism, atomic execution, evaluation of method expressions as background processes, and object protection.
The main contribution of this thesis is to develop a framework for supporting formal development of software in the extension of FOOPS mentioned above. In particular, we introduce a structural operational semantics for FOOPS, a notion of refinement for concurrent object oriented programs, congruence properties of refinement of FOOPS programs, and tools for mechanising refinement proofs.
The operational semantics is the core of the formal definition of FOOPS. It is used to define notions of refinement for FOOPS states, programs, and specifications. Those notions and associated proof techniques for proving refinement are used to illustrate stepwise formal development of programs in FOOPS. The congruence properties of refinement (with respect to some of FOOPS operators) justify compositional development of software in FOOPS. The tools help to validate the framework introduced in this thesis and motivate its use in practice.

Keywords: formal software development
object-oriented programming
refinement
concurrency
Advisor: Goguen, J
Three-dimensional unsteady gas turbine flow measurement

The high pressure turbine stage can be considered the most important component for the efficiency and longevity of a modern gas turbine. The flow field within this stage is highly complex and is both unsteady and three-dimensional. Understanding this flow field is essential if improvements are to be made to future engine designs.
Increasingly designers are placing more emphasis on the use of Computational Fluid Dynamics (CFD) rather than experimental results. CFD methods can be more flexible and cost effective. However before these predictions can be used they must be validated against experimental data at engine conditions.
The hostile environment and complexity of flows within a gas turbine engine mean that collection of experimental data is extremely challenging. This thesis describes the development of an instrumentation technique for unsteady gas turbine flow measurement capable of resolving unsteady three-dimensional flow. The technique is based on an aerodynamic probe constructed with miniature semiconductor pressure transducers manufactured by Kulite Semiconductor Inc.
Measurements recorded using this instrumentation technique from the Oxford Rotor experiment are presented to illustrate its use, and these in turn are compared with a CFD prediction of the rotor flow-field.
This work was funded by the Engineering and Physical Sciences Research Council and Kulite Semiconductor Inc. The Oxford Rotor project is jointly funded by the Engineering and Physical Sciences Research Council (EPSRC), and Rolls-Royce Plc.
Efficient numerical methods for ultrasound elastography

In this thesis, two algorithms are introduced for use in ultrasound elastography. Ultrasound elastography is a technique developed in the last 20 years by which anomalous regions in soft tissue are located and diagnosed without the need for biopsy. Due to this, the relativity cheap cost of ultrasound imaging and the high level of accuracy in the methods, ultrasound elastography methods have shown great potential for the diagnosis of cancer in soft tissues. The algorithms introduced in this thesis represent an advance in this field.
The first algorithm is a two-step iteration procedure consisting of two minimization problems - displacement estimation and elastic parameter calculation that allow for diagnosis of any anomalous regions within soft tissue. The algorithm represents an improvement on existing methods in several ways. A weighting factor is introduced for each different point in the tissue dependent on the confidence in the accuracy of the data at that point, an exponential substitution is made for the elasticity modulus, an adjoint method is used for efficient calculation of the gradient vector and a total variation regularization technique is used. Most importantly, an adaptive mesh refinement strategy is introduced that allows highly efficient calculation of the elasticity distribution of the tissue though using a number of degrees of freedom several orders lower than methods that use a uniform mesh refinement strategy. Results are presented that show the algorithm is robust even in the presence of significant noise and that it can locate a tumour of 4mm in diameter within a 5cm square region of tissue. Also, the algorithm is extended into 3 dimensions and results are presented that show that it can calculate a 3 dimensional elasticity distribution efficiently. This extension into 3-d is a significant advance in the field.
The second algorithm is a one-step algorithm that seeks to combine the two problems of elasticity distribution and displacement calculation into one. As in the two-step algorithm, a weighting factor, exponential substitution for the elasticity parameter, adjoint method for calculation of the gradient vector, total variation regularization and adaptive mesh refinement strategy are incorporated. Results are presented that show that this original approach can locate tumours of varying sizes and shapes in the presence of varying levels of added artificial noise and that it can determine the presence of a tumour in images taken from breast tissue in vivo.

Keywords: soft tissue
ultrasound
algorithm
modeling
elastography
Advisor: Chapman, J
Kay, D
Toward a divinised poetics: God, self, and poeisis in W. B. Yeats, David Jones, and T. S. Eliot

This thesis examines the traces of theological and broader religious discourses in selected works of three major twentieth-century poets. Each of the texts examined in this thesis encodes within its poetics a distinct, theologically derived conception of the ontological status of the self in relation to the Absolute. Yeats primarily envisions the relation as one of essential identity, Jones regards it as defined by alterity, and Eliot depicts it as dialectical and paradoxical.
Critics have underestimated the impact on Yeats’s late work of his final and most sustained engagement with Indic traditions, which issued from his friendship and collaboration with Shri Purohit Swami. Though Yeats projected Theosophical notions on the Indic texts and traditions he studied with Purohit, he successfully incorporated principles of Classical Yoga and Tantra into his later poetry. Much of Yeats’s late poetics reflects his struggle to situate the individuated self ontologically in light of traditions that devalue that self in favor of an impersonal, cosmic subjectivity.
David Jones’s The Anathemata encodes a religious position opposed to that of Yeats. For Jones, a devout Roman Catholic committed to the bodily, God is Wholly Other. The self is fallen and circumscribed, and must connect with the divine chiefly through the mediation of the sacraments. In The Anathemata, the poet functions as a kind of lay priest attempting sacramentally to recuperate sacred signs. Because, according to Jones’s exoteric theology, the self must love God through fellow creatures, The Anathemata is not only circular, forming a verbal templum around the Cross; it is also built of massive, rich elaborations of creaturely detail, including highly embroidered and historicized voices and discourses.
Critics have long noted the influence of Christian mystical texts on Eliot’s Four Quartets, but some have also detected a countercurrent within the later three Quartets, one that resists the timeless even as the poem valorizes transcending time. This tension, central to Four Quartets, reflects Eliot’s engagement with the dialectical theology of Karl Barth. Eliot’s deployment of paradox and negation does not merely echo the apophatic theology of the mystical texts that figure in the poem; it also reflects the discursive strategies of Barth’s theology. The self in Four Quartets is dialectical and paradoxical: suspended between time and eternity, it can transcend its own finitude only by embracing it.

Keywords: barth
eliot
quartets
yoga
modernism
religion
poetics
theology
tantra
poetry
jones
yeats
anathemata
theosophy
Advisor: Beasley, R