VictorJuiz/thesis huggingface dataset:
Combining regulatory angiogenic gene therapy and virotherapy for the treatment of breast cancer

This thesis describes the design of a virotherapy strategy capable of destroying both breast cancer vasculature and tumour cells, using an oncolytic adenovirus expressing angiogenesis-regulating proteins. Five oncolytic adenoviruses were compared to identify the best virotherapy agent for breast cancer, including measurement of cytotoxicity in vitro, and replication, intra-tumoural spread and anticancer efficacy in vivo. The viruses tested were Ad-dl922-947 (targets G1-S checkpoint defects); Ad-Onyx-015 and Ad-Onyx-017 (target p53/mRNA nuclear export defects); Ad-vKH1 (targets Wnt pathway defects) and AdEHE2F (targets estrogen receptor/G1-S checkpoint/hypoxia signalling defects).
AdEHE2F demonstrated optimal oncolytic activity and selectivity against breast cancer, accordingly this virus was engineered to express potent regulatory angiogenic proteins, namely soluble Flt1 and soluble Delta like-4 (Dll4). sFlt1 is the soluble extra-cellular domain of VEGFR1 and binds to and sequesters VEGF-A, thereby preventing VEGFR2 stimulation which is crucial to trigger angiogenesis. sDll4 is the soluble extracellular domain of Dll4 and has been previously shown to block Dll4/Notch signalling. Dll4/Notch signalling increases a chaotic and non-functional angiogenesis which ultimately delays tumour growth. Importantly, VEGF and Dll4 are the only angiogenesis genes reported to be haploinsufficient in vascular development and both have been shown to have a good anti-tumour effect.
sFlt1 and sDll4 genes were substituted for the viral genes E3 6.7K/gp19K of AdEHE2F, thereby using endogenous adenoviral machinery to drive production. The activities of AdEHE2F viruses expressing either sFlt1 or sDll4 were compared in vitro and in vivo. sFlt1 (expressed from AdEHE2F) inhibited endothelial cell proliferation and sprouting whereas sDll4 increased proliferation and branching in vitro. In vivo AdEHE2F expressing sFlt1 or sDll4 both showed superior anticancer activity compared to parental AdEHE2F, indicating at least additive efficacy between virotherapy and regulatory angiogenic approaches.

Keywords: cancer
breast cancer
angionenesis
oncolytic virus
gene therapy
Advisor: Seymour, LW
Local gradient estimate for porous medium and fast diffusion equations by Martingale method

This thesis focuses on a certain type of nonlinear parabolic partial differential equations, i.e. PME and FDE, which can be written as ∂tu = Δum with m > 0. Our aim is to derive better gradient bound in the form of
|∇u|2 (t,·) ≤ C   ||u(0,·)||k∞ − uk (t,·)
t ,  and   |∇u|2
uk1 ,  (t,·) −   ∂tu
uk2 ,  (t,·) ≤   C1
t ·
Chapter 1 consists of a survey on results related to PME and FDE, and a short review on some works about deriving gradient estimates in probabilistic ways.
In Chapter 2 we estimate gradient on space variables of solutions to the heat equation on Euclidean space. The main idea is to construct two semimartingales by letting the solution and its gradient running backward on the path space of a diffusion process. Estimates derived from decompositions of those two semimartingales are then combined to give rise to an upper bound on gradient that only involves the maximum of the initial data and time variable. In particular, it is independent of the dimension.
In Chapter 3 we carry the idea in Chapter 2 onto the study of positive solutions to PME or FDE, and obtained a similar type of bound on |∇u| for local solutions to PME or FDE on Euclidean space. In existing literature there have always been constraints on m. By considering a more general form of transformation on u and introducing a family of equivalent measures on path space, we add more flexibility to our method. Thus our result is valid for a larger range of m. For global solutions, when m violates our constraint, we need two-sided bound on u to control |∇u|.
In Chapter 4 we utilize maximum principle to derive Li-Yau type gradient estimate for PME on a compact Riemannian manifold with Ricci curvature bounded from below. Our result is able to yield a Harnack inequality possessing the right order in time variable when the lower bound of Ricci curvature is negative.

Keywords: Aronson-Benilan estimate
Porous medium equation
Martingale
Curvature-dimension condition
Fast diffusion equation
Advisor: Qian, Z
The God of possibility and promise: Christian eschatology as a response to technological futurism

The explosive growth of technology today is causing extensive speculation about the future. These ‘technological futurisms’—especially transhumanism—are often imbued with religious value by their adherents. How should Christians respond to the content of technological futurisms and also the way the future is constructed? In this thesis I argue that Christian eschatology has a more robust understanding of the future than technological futurism, as championed by transhumanism, and can allow for radical hope while also maintaining important humanistic virtues which are ultimately lost in transhumanism. Christian eschatology does not only depend on what is actual to create its future. Rather, it is open to the God of possibility and promise who can bring the radically new in the Kingdom of God.
This dissertation is broken into three major sections with an introductory and concluding chapter. The first section provides a history of our technological imagination today by looking at visionary approaches to technology and the future in both technological utopias and science fiction. This history provides the conditions for understanding the proposed future of transhumanism. The second section orients the final response by assessing technology and the future in the eschatologies of Pierre Teilhard de Chardin and Jacques Ellul. Both Teilhard and Ellul agree that the technological future without appeal to the Christian God is dangerous. The final section looks at the theological and philosophical issues surrounding technology and the future. Heidegger’s works are used to sharpen themes related to technology and the future; in particular, how technology is related to ontology and how the future is related to possibility. The final chapters construct a Christian response to transhumanism around the themes of possibility and promise by utilising the works of Richard Kearney, Eberhard Jüngel and Jürgen Moltmann. A Christian notion of possibility allows for the radically new in a way transhumanism does not and the Christian idea of promise safeguards human virtues by emphasising the interpersonal as ultimate rather than self-transcendence as with transhumanism.

Keywords: Religion and Culture
Philosophy of Religion
Christian Eschatology
Technology
Advisor: Pattison, G
Surface active polymers as anti-infective and anti-biofouling materials

This thesis is concerned with the chemical modification of polymers in the preparation of a library of materials which exhibit altered surface properties as a result of the surface chemical functionality, with particular emphasis on the development of materials that control biofouling and are antibacterial. Chemical modification of crosslinked polystyrene, in film and microsphere form, was carried out by carbene insertion followed by diazonium coupling. This provided access to a collection of materials with varying surface chemistry, whilst the bulk properties of the polystyrene substrates were maintained. Synthesis of the diaryldiazo and the diazonium salts used to perform the surface modifications is described, as well as the preparation and characterisation of the materials.
Analysis of the ability of the materials to adsorb and bind the protein bovine serum albumin (BSA) is presented with data obtained from two methods of observation. Quartz Crystal Microbalance with Dissipation (QCM-D) and a protein assay based on the change in optical density of a BSA/PBS solution are used to demonstrate how the specific surface chemistry of the materials influences the ability to adsorb and bind protein. The behaviour of the materials was time dependent and was rationalised with respect to the surface water contact angle and the calculated parameters polar surface area and % polar surface area of the functional groups added to the surfaces.
Finally, penicillin loaded materials were prepared and their antibacterial activity was tested against E. coli and S. aureus, demonstrating that the antibiotic is still active from within the polystyrene scaffold.

Keywords: organic chemical coatings
surface chemistry control
antibacterial surfaces
Advisor: Moloney, M
Foord, J
Exploring the roles of LIM domain binding proteins in zebrafish development

As some of the most important and widely utilised intercellular signalling molecules, transforming growth factor βs (TGFβs) play critical roles in normal development and in human disease. Establishing appropriate levels of signalling involves positive and negative feedback, driven by the same signal transduction components, but whether or how the two are distinguished has not previously been understood. Here we show that LIM domain binding proteins (Ldbs) drive the Smad6/7-mediated negative feedback of TGFβ signalling, but they are not required for the ligand-driven positive feedback or other downstream transcriptional activation. In Ldb-deficient zebrafish embryos, the homeostasis of TGFβ signalling is perturbed. As a consequence, signalling of TGFβ family members, Nodal and BMP, is stably enhanced, giving rise to excess mesoderm and endoderm, an effect that can be rescued by reducing Nodal and BMP. Later in development, conditional ldb2a knockdown causes defective vascular, angiogenic and haemogenic development, likely also by elevating TGFβ signalling. Thus, Ldbs control the homeostatic regulation of TGFβ signalling and therefore play critical roles in diverse developmental processes.

Keywords: Zebrafish
Development
Ldb
LIM domain
TGFb
Auto-regulatory feedback loops
Advisor: Patient, R
Sententiae Jesu

This dissertation coordinates two problems which have hitherto resisted adequate synthesis: the form-critical problem of describing proverbial-sounding Synoptic sayings and the tradition-historical problem of assessing the rhetorical habits of Jesus and his immediate successors in oral tradition. The approach taken here to linking these qualifies not only form-critical assumptions of continuity between written forms - in Kleinliteratur - and identifies oral Sitze im Leben of mnemotechnical scholasticism, but also of the recent emphases on radical discontinuity between oral and writing modes of tradition. The connection proposed here between re-description of so- called Wisdom-sayings and oral traditional aspects of the gospels is in the Hellen educational category of gnome. Defined, exemplified and prescribed in basic Graeco-Roman educational texts as well as in technical, philosophical manuals of Rhetoric and in a rich collection-literature, gnome is superbly attested as an exercise in primary education, in all kinds of public-speaking and in cross-cultural (including Jewish) tradition. Moreover, Hellenistic cultivation of gnome primarily as a speech-type, indeed as a conversational means of argumentation in any Sitz im Leben, and only secondarily though still extensively as a literary technique makes it a particularly pertinent term of comparison for New Testament criticism. Recognizing gnomic continuity between oral and written Synoptic tradition allows discussion of the authenticity not only of individual sayings (on criteria of dissimilarity), but also collectively of the gnomic manner (on criteria of oral-literate continuity and multiple attestation): quite apart from the (in)authenticity of each gnome, gnomic style is central to Jesus' self-expression and earliest tradition. In this sense gnomai are a particularly valuable data-set for reassessing the critically controverted relationship between Jesus' rhetoric and law: in Synoptic tradition gnome is exploited suggestively as a non-legal means of addressing conventionally legal topics.
The theology of the corporation

This essay presents evidence that the institution of the corporation has its origins and its main developmental 'epochs' in Judaeo-Christian theology. The notion of the nahala as the institutional symbol of the Covenant between YHWH and Israel is a primal example of the corporate relationship in its creation of an identity independent of its members, its demand for radical accountability on the part of its members, and in its provision of immunity for those who act in its name. On the basis of the same Covenant, St. Paul transforms an ancillary aspect of Roman Law, the peculium, into the central relationship of the Christian world through its implicit use as the institutional background to the concept of the Body of Christ. The exceptional nature of this relationship allows the medieval Franciscans and the papal curia to create what had been lacking in Roman Law, an institution which can own property but which cannot be owned. This relationship is subsequently theorized as the Eternal Covenant by Reformed theologians and successfully tested in one of the greatest theological/social experiments ever recorded, the 17th century settlement of North America. The alternative 'secular' explanation of the corporation provided by 19th century legal philosophy relies implicitly on the theological foundations of the corporation and remains incoherent without these foundations. The theological history of the corporation was recovered in the findings of 20th century social scientists, who also identified corporate finance as the central corporate activity in line with its Levitical origins. Although the law of the corporation is secular, the way in which this law was made a central component of modern life is theological. Without a recovery of this theological context, the corporation is likely to continue as a serious social problem in need of severe constraint.

Advisor: Wannenwetsch, B
Factorisation in relational databases

We study representation systems for relational data based on relational algebra expressions with unions, products, and singleton relations. Algebraic factorisation using the distributivity of product over union allows succinct representation of many-to-many relationships; further succinctness is brought by sharing repeated subexpressions. We show that these techniques are especially applicable to results of conjunctive queries.
In the first part of the dissertation we derive tight asymptotic size bounds for two flavours of factorised representations of results of conjunctive queries. Any conjunctive query is characterised by rational parameters that govern the factorisability of its results independently of the database instance. We relate these parameters to fractional edge covers and fractional hypertree decompositions.
Factorisation naturally extends from relational data to its provenance. We characterise conjunctive queries by tight bounds on their readability, which captures how many times each input tuple is used to contribute to an output tuple, and we define syntactically the class of queries with bounded readability.
In the second part of the dissertation we describe FDB, a relational database engine that uses factorised representations at the physical layer to reduce data redundancy and boost query performance. We develop algorithms for optimisation and evaluation of queries with selection, projection, join, aggregation and order-by clauses on factorised representations. By introducing novel operators for factorisation restructuring and a new optimisation objective to maintain intermediate and final results succinctly factorised, we allow query evaluation with lower time complexity than on flat relations. Experiments show that for data sets with many-to-many relationships, FDB can outperform relational engines by orders of magnitude.

Keywords: Factorisation
Query Processing
Algorithms
Relational Databases
Advisor: Olteanu, D
Derived symplectic structures in generalized Donaldson–Thomas theory and categorification

This thesis presents a series of results obtained in [13, 18, 19, 23{25, 87]. In [19], we prove a Darboux theorem for derived schemes with symplectic forms of degree k < 0, in the sense of [142]. We use this to show that the classical scheme X = t0(X) has the structure of an algebraic d-critical locus, in the sense of Joyce [87]. Then, if (X, s) is an oriented d-critical locus, we prove in [18] that there is a natural perverse sheaf P•X,s on X, and in [25], we construct a natural motive MFX,s, in a certain quotient ring MμX of the μ-equivariant motivic Grothendieck ring MμX, and used in Kontsevich and Soibelman's theory of motivic Donaldson-Thomas invariants [102]. In [13], we obtain similar results for k-shifted symplectic derived Artin stacks.
We apply this theory to categorifying Donaldson-Thomas invariants of Calabi-Yau 3-folds, and to categorifying Lagrangian intersections in a complex symplectic manifold using perverse sheaves, and to prove the existence of natural motives on moduli schemes of coherent sheaves on a Calabi-Yau 3-fold equipped with 'orientation data', as required in Kontsevich and Soibelman's motivic Donaldson-Thomas theory [102], and on intersections L∩M of oriented Lagrangians L,M in an algebraic symplectic manifold (S,ω). In [23] we show that if (S,ω) is a complex symplectic manifold, and L,M are complex Lagrangians in S, then the intersection X= L∩M, as a complex analytic subspace of S, extends naturally to a complex analytic d-critical locus (X, s) in the sense of Joyce [87]. If the canonical bundles KL,KM have square roots K1/2L, K1/2M then (X, s) is oriented, and we provide a direct construction of a perverse sheaf P•L,M on X, which coincides with the one constructed in [18].
In [24] we have a more in depth investigation in generalized Donaldson-Thomas invariants DTα(τ) defined by Joyce and Song [85]. We propose a new algebraic method to extend the theory to algebraically closed fields K of characteristic zero, rather than K = C, and we conjecture the extension of generalized Donaldson-Thomas theory to compactly supported coherent sheaves on noncompact quasi-projective Calabi-Yau 3-folds, and to complexes of coherent sheaves on Calabi-Yau 3-folds.

Keywords: derived algebraic geometry
Donaldson-Thomas invariants
Advisor: Joyce, D
Towards an ecumenical ethic

This thesis is concerned to further the renewal of moral theology in an age of ecumenism by drawing three of its important contemporary protagonists - Germain Grisez, Stanley Hauerwas and Oliver O'Donovan - into an ecumenical dialogue in the hope of reconciling their different approaches. This dialogue occurs in five stages. First, the question, what makes Christian ethics Christian? is considered using O'Donovan's and Hauerwas' emphasis on the distinct epistemological foundations and content of a Christian ethic as a benchmark. An interpretation of Grisez's natural law ethic is then offered which satisfies these conditions. Secondly, the relationship between O'Donovan's and Grisez's essentially realist theories is considered. The difference between them emerges as being primarily one of emphasis, with O'Donovan giving priority to the need for a Christian ethic to be unequivocally realist, while Grisez focuses on the need for sound philosophical argument. A reconciliation of their approaches which seeks to do justice to both sets of concerns is then suggested in the form of a Christian realist theory. Thirdly, a careful interpretation of Hauerwas' narrative ethic, which suggests that it is less subjectivist than is usually thought to be the case, provides the basis for its reconciliation with a Christian realist theory as a complementary form of ethics. An exploration of the possibilities and limitations of narrative for moral deliberation suggests that such a complementary relationship is necessary. Fourthly, the possibility of such a relationship is secured when an analysis of Grisez's theory reveals that it is capable of meeting Hauerwas' concerns about the centrality of character, the particularity of the person in shaping moral obligations and the place of the emotions in the moral life. Finally, it is concluded that the ecumenical ethic towards which the thesis moves will be one which describes this complementary operation of a Christian realist theory and a narrative ethic from the perspective of Christian worship.
Towards quantum superpositions of a mirror

In principle Quantum Mechanics allows the creation of macroscopic mass superposition states - so called "Schrödinger Cat States". This has not been confirmed experimentally largely due to the difficulty of isolating such states from environmental decoherence. It is of interest to create massive superpositions both in order to test Quantum Mechanics and to shed light on the elusive 'measurement problem'. This thesis presents the theoretical analysis of, and the initial experimental steps towards, an ambitious proposal to test the superposition principle of Quantum Mechanics at the 10-12 kg-scale, approximately nine orders of magnitude more massive than any superposition observed to date.
The experimental principle is that a small mirror mounted on a micro-mechanical oscillator (cantilever) forms one end of a high-finesse cavity in one arm of a Michelson interferometer and is coupled to a single photon by radiation pressure. The photon, in a superposition of each arm, and the cantilever evolve into a superposition involving two distinct locations of the cantilever. By observing the interference of the photon only, one can study the creation and decoherence of the combined state.
Firstly, a detailed analysis of the experimental requirements is given based on (1) the need for sufficient momentum transfer from the photon to displace the micro-mirror/cantilever to a distinguishable degree, (2) the need to isolate the cantilever to avoid significant environmental decoherence, and (3) the need to have sufficient interferometric stability to perform the measurement. An iterative analysis was performed to optimise these to a set that is feasible with current technology. This demands: (1) cavity mirrors with a reflectivity of R ≥ 0.9999998 at visible wavelength, (2) a system temperature of ≤ 3mK, (3) a cantilever mechanical quality Q ≥ 105 , (4) a vacuum with gas particle density of 1012/m3, (5) a relative position stability of the cavity mirrors of ≤ 10-13 m/min, and (6) optical mirror switching to 50% for ≤ lμs. Whilst extremely demanding, all of these goals appear to be within reach of current technology.
Secondly, initial experimental results are described: (1) the fabrication of a 10μm radius dielectric mirror designed for peak reflectivity R > 0.99997 and the attaching of this to an AFM-type cantilever of mechanical quality Q > 4 x 104 ; (2) the alignment of a cavity of length 2.5cm involving this micro-mirror/cantilever at one end and the demonstration of a finesse of F > 1000 using two independent measurement techniques. The diffraction losses for the cavity are calculated numerically to be < 10-6 . Other mechanisms limiting the finesse are investigated and the dominant one is determined to be accoustic noise which can be alleviated by placing the cavity into a vacuum. In addition, results demonstrating ultra-fast optical switching of high reflectivity mirrors are shown.

Advisor: Bouwmeester, D
Penrose, R
Dik Bouwmeester and Roger Penrose