VictorJuiz/thesis huggingface dataset:
Developing anti-p53/HLA-A*0201 T-cell receptor mimic antibodies for cancer immunotherapy
Keywords: p53
MHC class I presented peptide
Cancer immunotherapy
Therapeutic antibody
T-cell receptor-like (TCR-like) antibody
T-cell receptor mimic (TCRm) antibody
HHD mouse
CAR T-cell
T-cell epitope
p53 peptide

T-cell receptor mimic (TCRm) antibodies target a dual antigen epitope consisting of a peptide derived from an intracellular protein, and the major histocompatibility complex class I (MHC-I) molecule that presents the peptide at the cell surface. As traditional antibodies typically target cell surface or secreted antigens, TCRm antibodies advantageously expand the range of targetable antigens to include peptides derived from intracellular proteins.
This thesis describes the development of TCRm antibodies targeting peptides that are derived from the wild type p53 protein and are presented by human leukocyte antigen (HLA)-A2. We further characterised the specificity and safety of the T1-116C TCRm antibody, which was the most extensively studied TCRm antibody in the laboratory prior to the start of this DPhil project. We showed that T1-116C labels primary AML and myeloma cells. We investigated the specificity of the T1-116C TCRm antibody for the p5365-73 peptide, RMPEAAPPV, by substituting each amino acid within the peptide individually, and showed that T1-116C recognises multiple tumour antigens. Using in silico analysis we identified 271 potentially cross-reactive peptides. We tested a panel of 25 peptides that are conserved in mice in vitro, showing that T1-116C binds peptides derived from a broad range of normal tissues. Despite these findings, in vivo testing of T1-116C cross-reactivity in human HLA-A2 transgenic mice demonstrated that T1-116C does not cause toxicity to normal mouse tissues.
We also generated chimeric antigen receptors (CARs) for T-cell therapy using the single chain variable fragment of p53-targeting TCRm antibodies to provide the CAR specificity. We found that the CAR derived from T2-2A, a TCRm antibody that targets the p53187-197 peptide, GLAPPQHLIRV, demonstrated superior specificity for target peptide-HLA-A2 tetramers and cell lines to the T1-116C CAR. Through these studies, the T2-2A TCRm antibody has emerged as a potential therapeutic agent when used in the CAR format.
The history and viability of constitutivism in ethics
Keywords: Constitutivism
Immanuel Kant
Plato
Christine Korsgaard
Kantian ethics

The topic of this thesis is constitutivism in ethics: its history and its viability. Constitutivists hope to show that moral standards are normative because if we are not following them, we are failing to be agents. We cannot escape trying to be agents: it is just our way of trying to do anything in particular. In failing to be agents, then, we are failing to do what we ourselves are trying to.
The force of normativity, on a constitutivist view, turns out to be the force of our own efforts to do things. Moral or pro-moral standards are what we must be guided by for our own attempts to do things to be internally consistent. The immoral would-be agent, then, is one who is divided against themself. They are trying to do the impossible: to be agents in a way that agents cannot.
Defending the viability of constitutivism – one half of my topic – only takes defending one form of it. This thesis focuses on Kantian constitutivism, which may be the most promising kind of it. It focuses in particular on Christine Korsgaard’s version of that position, as presented in The Sources of Normativity, Self-Constitution, her recent Fellow Creatures, and a range of essays.
The four substantive chapters of this thesis set out to answer four different questions. The first is what the components of Kantian constitutivism are. Two of those four components are claimed to be characteristic of constitutivism in ethics, and the chapter points to the historical background of all four of them. The second question is in what sense we face the problem of agency. The chapter first distinguishes rational and nonrational agency. It then explains how, on the view, rationality is self-conceptual, and attempts to pin down this talk of problem-facing.
The final two chapters of this thesis take up two closely related questions. These are why our moral psychology should feature what Kant calls “incentives,” and why, as Kant and Aristotle believe, it should feature not just acts, but ends. It argues that on the Kantian constitutivist picture, there are two demands on a moral philosophy of action. Those demands can be seen to generate the functional concepts of incentives and, via the steps of a Kantian moral argument, ends.
Essays on the new financial landscape
Keywords: CCP
cryptocurrency
global games
relationship lending
networks
credit crunch
blockchain

This dissertation consists of three essays, each examining the implications of a major change to the financial landscape over the past decade.
In the first essay, I show that price formation for cryptocurrencies is markedly different from that for other asset classes. I study two distinctive characteristics of cryptocurrencies. First, the blockchain structure of cryptocurrency means that there is a limit on the number of transactions that can be settled in any given time. Second, as a cryptocurrency is a form of money not backed by any asset class, its value depends on the extent to which it is used as a means of payment. Taken together, these characteristics mean that speculative activity can crowd out payment usage. Trading can lower the price of the asset, even when it is buy-side trading. I show that this may explain high price volatility.
In the second essay, we propose a novel channel for credit crunches. A borrower fears that there will be distress in the financial sector, in which case her relationship lender may not be able to finance her project. To insure against this risk, she chooses a smaller project that uninformed outsiders would be willing to finance. Financial distress therefore leads to lower investment, but not via the usual supply or demand side channels. We show that a small increase in distress risk can lead to a large downward jump in investment. This is joint work with Alan Morrison and Joel Shapiro.
Finally, the third essay examines how derivatives trading networks are affected by the introduction of mandatory central clearing. There can be a trade-off: central clearing can increase the mean of net exposures, but reduce the variance. We show that the trade-off can never be in the other direction. This suggests that, the more risk-averse agents are, the beneficial central clearing is likely to be. This is joint work with Rodney Garratt.
Why are statements unable to receive contraries over time?
Keywords: Contraries
Substance
Categories
Statements
Aristotle
Time

In Categories chapter 5 [4a10-4b19], Aristotle sets out to defend the claim that primary substances are the only individual existents which admit of receiving contrary attributes over time. To perform this task, he considers whether a statement may also admit of receiving contraries. It is the contention of this study that Aristotle disqualifies simple present-tensed statements from admitting of receiving contraries in their own right, by only allowing for the same statement to admit of receiving contrary attributes over time in an incidental sense. Aristotle’s chosen strategy for defending this stance consists in a progressive refinement of the realist account of truth-making which he lays out in Cat.12. This leads up to his endorsement of a deflationary version of this account, which accommodates temporalist assumptions. Upon the interpretation of this deflationary account of truth-making which is here proposed, a statement which admits of being true and false at different times may not enjoy the attribute true or its contrary, false, in itself, but only in relation to an actual entity other than itself and, thus, incidentally. As a result, a statement may only incidentally come and cease to be true and false over time. Since a statement cannot change from being-true to being-false (or vice-versa) in a genuine sense, but an individual existent only admits of receiving contraries by being able to change, a statement may not receive contrary attributes over time in a genuine sense. Thus, a statement which admits of being true and false at different times is not, strictly speaking, able to receive contraries.
Unsymmetrical group 4 permethylindenyl ansa-metallocenes as polymerisation catalysts
Keywords: Metallocene
Lactide
Catalysis
Ethylene
Polymerisation

The primary aims of the thesis were to: (i) discover catalyst systems that maintained high α-olefin polymerisation activities in the presence of hydrogen while producing polymers with low molecular weights (Mw <10 kg mol−1) and (ii) find new single-site initiators for the ring-opening polymerisation (ROP) of lactide monomers.
The thesis begins by offering a brief introduction to α-olefin and lactide polymerisation, including discussions on known polymerisation catalysts. The synthesis and characterisation of a series of well-defined group 4 ansa-bridged permethylindenyl complexes based on the Me2SB(CpR,I*)ZrX(Y) ({(η5-C9Me6)Me2Si(η5-C5H3R)}ZrX(Y) where R = H, Me and nBu) motif is then discussed. The application of these complexes as α-olefin polymerisation catalysts, both in solution-phase and when immobilised on a range of inorganic solid supports (MAO modified silica, MAO modified layered double hydroxide and solid MAO) is then detailed. It was found that solid MAO supported catalytic systems exhibited some of the highest slurry-phase polymerisation activities reported in the literature. The systems produced HDPE with minimal branching, uniform polymer morphology and low polymer molecular weights (Mw <100 kg mol–1 at 80 °C). A variety of polymerisation conditions were studied, including the effects of temperature, scale, pressure, scavenger, catalyst loading and time.
The slurry-phase ethylene/1-hexene copolymerisation ability of the catalysts is then demonstrated. The effects of hydrogen on ethylene polymerisation activity and polymer properties are also discussed. The overall effect of 1-hexene was found to depend on the identity of the catalyst and the amount of co-monomer in the system. All catalysts demonstrated remarkable stability in the presence of hydrogen, which was accompanied by a significant decrease in polymer molecular weights to produce commercially viable polyethylene waxes.
Finally, four unsymmetrical permethylindenyl zirconocenes are presented as initiators for the ROP of L-, D- and rac-lactide. The kinetics of polymerisation, overall rate equations and the effects of temperature, initiator concentration, scale and co-initiator concentration are discussed. A variety of techniques were used to characterise the polymers in order to deduce tacticity, molecular weights and chain end groups.
Mentality as nonderivative intentionality
Keywords: Mental
Phenomenal
Tim Crane
Intentionality
Mentality
Intentionalism
Nonderivative
Intentional
Mental representation
Qualia

I here advance the following deductively valid argument:
P1. For all x, if x is mental, x is intentional.
P2. For all x, if x is mental and intentional, x is nonderivatively intentional.
P3. For all x, if x is nonderivatively intentional, x is mental.
––––––
C. For all x, x is mental if and only if x is nonderivatively intentional.
I thus maintain that all and only mental phenomena are nonderivatively intentional – that nonderivative intentionality is ‘the mark of the mental’. The simplest explanation for this fact is that mentality consists in nonderivative intentionality.
Development of MKID Instrumentation for exoplanet direct imaging
Keywords: Exoplanets
Instrumentation

Microwave Kinetic Inductance Detectors (MKIDs) are a highly sensitive cryogenic photodetector. These devices operate by measuring the increase in the surface impedance of a superconducting film when Cooper Pairs are broken by incident photons. This technique allows MKIDs inherent spectral resolution and instantaneous read out with essentially no false counts. In contrast to other cryogenic detectors, the intrinsic multiplexing of the pixels in frequency domain means that arrays of several tens of thousand of pixels can be readout with just a few feed-lines using room temperature radio electronics. These unique properties make MKIDs potentially transformative for exoplanet direct imaging, where residual speckle noise currently limits the minimum mass of the discernible exoplanets to several Jupiter masses. In this thesis I describe some of the developments of MKID instruments required for exoplanet imaging, and I investigate the potential of MKIDs to provide new discoveries in this field.
One of the required developments was the automation of the tuning of pixel biasing prior to taking a set of observations. Previously this required inspecting the transmission profile of each pixel by eye and then selecting the optimal power. For the large format arrays necessary for exoplanet direct imaging (on the order of tens of thousand pixels) this process can take approximately 24 human hours to complete. I show that a machine learning-based algorithm can replicate this process in a matter of minutes with equivalent accuracy to that of humans when compared to a control dataset. I then discuss an extension to this algorithm that should enhance the phase measurement performance of MKIDs, ultimately improving the limiting mass of detected exoplanets.
Simulation software was developed to make pragmatic predictions on the capabilities of MKIDs for exoplanet direct imaging. This software demonstrates the utility of Dark-Speckle Imaging discrimination technique for a realistic MKID device with appropriate limitations such as maximum count and reduced pixel yield. Possible extensions to this technique that exploit the wavelength dependence of speckles are also explored, which are found to yield superior performance to standard differential imaging methods. I also make predictions on the performance of a next generation MKID-based instrument systems. Preliminary results show that this system can achieve the contrast performance necessary for Neptune sized exoplanets and below.
Finally, I present on-sky results of planetary nebula NGC 6751 taken with the ARCONS MKID instrument at Palomar. The inherent spectral resolution of the device meant that a low resolution spectrum of the central star could be created that provided further evidence to clarify its spectral type. The central star was also explored in the time domain at the fine resolution of MKIDs. No periodic feature was found on the time scale of the observation.
Moving Muslims: the great northwestern rebellion and the transformation of Chinese Islam, 1860-1896
Keywords: Qing
Sufism
Zuo Zongtang
Islam in China
Linxia
Empire
Hui
Great Northwestern Muslim Rebellion

This thesis explores the history of an empire’s attempt to remake its Muslim subjects. The reconstruction process that followed the Great Northwestern Muslim Rebellion (1860-1874) was a highly ambitious project of social engineering that strove not to resurrect the antebellum order, but to transform the entire northwest. Governor-General Zuo Zongtang proposed the resettlement of thousands of Chinese Muslims (Hui) away from their Han Chinese neighbours, on the grounds that separating the two groups was the only way to ensure that violence would not reoccur.
Based on extensive archival research using a local Qing county archive combined with gazetteers, Muslim histories, interviews and stele from local areas, this thesis opens with a revisionist history of the role Sufi paths played in the 18th century extension of Qing empire into Gansu’s Sino-Tibetan fringes. Whilst the Sufi paths were politically dominant in He-Huang prior to the Great Northwestern Rebellion, the reconstruction period fundamentally changed the structures of everyday life and governance. The new clusters of Muslim settlement and rise of generation of military elites in the postbellum period produced the conditions for a religious revival which ultimately ended the political role of Sufi lineages in borderland life and created the conditions for the arrival of currents of Islamic reformism in China. This outcome is the product of the complex interplay of a new nationalism with older Qing ideas of empire and ethnicity, and of the local, half-implemented reconstruction project that remade the Gansu-Qinghai social world in unanticipated ways. The legacy of the resettlements, however, lives on in the process of minoritization it catalysed: Muslims in China today are considered an entirely separate ethnicity from the Han. Overall, this thesis describes two parallel arcs: the rise and fall of China’s Sufi paths and the rise of the Muslim nationalist military lineages, who would become the Republican-era ‘Muslim warlords’.
Volcanic ash in the atmosphere
Keywords: Refractive index
Volcanic aerosols
Volcanic ash
Optical properties
Air quality
Chemical composition

This thesis presents new work on the characterisation of volcanic ash in the atmosphere. The eruption of Eyjafjallajökull in 2010 brought the issue of ash in the atmosphere into sharp focus. Radiative transfer models used in remote sensing and hazard assessment of volcanic ash require knowledge of ash optical parameters, which are governed by the spectral complex refractive index (n + ik: where n is the real and k is the imaginary part). By investigating the relationship between volcanic ash composition and refractive index, a new parameterisation has been developed which will aid in the detection and quantification of hazardous ash clouds. It has been tested on retrievals from three recent eruptions using Infrared Atmospheric Sounding Interferometer (IASI) satellite data. The eruptions of Chaitén (Chile) in May 2008, Okmok (Aleutian Peninsula) in July 2008 and Grímsvötn (Iceland) in May 2011 allowed the testing and application of the parameterisation on a range of compositions, demonstrating that use of a parameterised index may significantly improve the retrieval of mass loading, a crucial parameter for assessing hazards to health, infrastructure and aviation. Direct sampling techniques are required to supplement satellite observations in order to ground-truth remote sensing techniques. A study of aerosol samples collected in the UK when the ash plume of Eyjafjallajökull was overhead has demonstrated that volcanic ash is chemically detectable above urban particulate matter, and that ash surface chemistry plays an important role in transporting heavy metals, which may have implications for remote sensing.
Free-flight kinematics of diptera
Keywords: biomechanics
insect flight
kinematics

Insect flight is a complex behaviour that goes beyond pure mechanism. Integrating genetics, morphology, physiology, sensorimotor control, kinematics and aerodynamics, researching the multiform nature of insect flight is of great scientific interest and also a challenge. Consequently, exploring different strategies for reducing the dimensionality of large flight datasets to uncover meaningful relationships is critical to furthering our understanding of insect flight biomechanics. The aim of my DPhil is to explore different strategies for analysing large datasets of free-flight kinematics in three Dipteran species: Drosophila melanogaster (fruit fly), Calliphora vicina (blowfly) and Eristalis tenax (drone fly). In Chapter 2, I critically evaluate the k-means clustering algorithm as a means of partitioning dipteran body kinematics, and show that it is an unsuitable target for body kinematic data that shifts continuously. In Chapter 3, I show that sexual dimorphism in fruit flies affects their wing beat kinematics beyond size dimorphism. In Chapter 4, I used the k-nearest neighbour clustering algorithm to develop a way of predicting the gear stops that blowflies engage in based on their wing beat kinematics. In Chapter 5, I contrast the wing beat kinematics and aerodynamic profile of all three species. Overall, my thesis shows firstly, that fruit flies, blowflies and drone flies occupy distinct kinematic morphospaces, and secondly, that careful consideration should be given to the choice of technique used to reduce the dimensionality of the data.
The dramatic ecologies of As You Like It
Keywords: ecology
form; formalism
gender
intertextuality
class
myth
race
heteroglossia
slavery
archetype
subjectivity
ecocriticism
interpretation

This thesis reads As You Like It’s various cultural perspectives as dramatic ecologies. At their intersections, where characters describe and respond to each other, they combine and clash, exposing linguistic and dramatic traces of these ecologies, which appear as multidimensional signs – words, ideas, and mythical archetypes leading to multiple narrative subtexts. They create polysemic sites of possible interpretations, introducing potentially related but non-identical realities, simultaneously copresent in the forest playspace, constructing the conditions for emerging subjectivities. My analysis is both historical, attending to the unique cultural issues of each character’s world, and critical, considering the resonances of verbal repetitions and conceptual dissonances, foregrounding imbricated issues such as technology’s cultural impact, class conflict, women’s literacy, and Elizabethan race relations. My research is intertextual, addressing the play’s literary and historical precursors, including Ovid’s Metamorphoses, Lodge’s Rosalind, The Fairie Queene and Sidney’s Arcadia, as well as intratextual, considering the interaction of these discourses as they connect in Arden.
Beginning with Jaques, I address the forest’s Ovidian, Pythagorean cosmology, before exploring Touchstone’s contrasting approach to time and technology, and the influences of Rabelais and commedia dell’arte in the clown’s ecology, with its emphasis on conditionality. Chapter three analyses Corin’s work ethic (both social and physical), his cultural relativism, his role as guide to the forest society, and his poetic language, with its links to the tradition of classical and Elizabethan literary pastoral. Chapter four traces race and writing in Phoebe’s ecology, emphasising her role as social scapegoat, and chapter five considers Orlando’s heroic encounter with regard to its potential relevance for the other characters’ intertwined psychic journeys. Chapter six addresses Rosalind’s alchemical shapeshifting and literary self-expression as she negotiates Elizabethan gender norms; inhabiting the contrasting interpellations of other ecologies, she exemplifies the exiles’ citational, emergent subjectivity, which parallels audience responses to interpretive possibilities.