VictorJuiz/thesis huggingface dataset:
One-pot nitro-Mannich cascade reactions: new methodologies and synthetic applications
Keywords: diastereoselective
methodology
multi-component reaction
enantioselective
nitro-Mannich
Slaframine
cascade

Pyrrolidine and pyrrolidinone rings are common motifs found in many biologically active natural products and drugs. Accordingly, our work focuses on the development of new methodologies for their one-pot synthesis.
An efficient diastereoselective nitro-Mannich / lactamisation reaction cascade of methyl 3-nitropropanoate with cyclic and acyclic imines for the direct preparation of trans-monocyclic and fused tricyclic pyrrolidinone derivatives was developed. The reaction is easy to perform, broad in scope and tolerates a wide variety of functional groups. For the monocyclic methodology, 28 examples with a very good average yield of 72% and excellent diastereocontrol (typical dr >98:2) were obtained using optimized conditions and varying the amine and the aldehyde reagents.
The methodology has been extended to the synthesis of 1,3,5-trisubstituted 4-nitropyrrolidinone derivatives using α-substituted 3-nitropropanoate. Using a one-pot protocol, 22 derivatives were synthesised in good yields (65% average) and diastereomeric ratios ranging from 3:1 to 30:1 in favor of the trans/trans diastereoisomer.
In addition, the nitro-Mannich / lactamisation cascade of methyl 3-nitropropanoate was developed further to allow the rapid synthesis of 5-isopropyl-4-nitropyrrolidin-2-one from reaction with ammonium acetate and 1-butyl-4-nitropyrrolidin-2-one from reaction with formaldehyde. Also, the synthetic utility of the nitro-pyrrolidinones formed was exemplified through various functional group modifications: the selective reduction of the lactam carbonyl, the reduction of the nitro group in the presence or absence of a carbonyl group and the reductive removal of the nitro group.
The development of an enantioselective version of the cascade under chiral Brönsted acid catalysis provided promising results (up to 90% ee). Moreover, various studies were undertaken to understand the mechanism of the reaction and the nitro-Mannich / latamisation cascade is now well understood. Furthermore, a formal synthesis of rac-Slaframine in 8 steps and 15% overall yield was achieved and it inspired additional work towards a nitro-Mannich / epoxide ring opening cascade.
Polytopes, scattering amplitudes, and cohomology
Keywords: Scattering Amplitude
Polytope
Volume
Cohomology
Triangulation

We introduce a new definition of abstract polytope in any dimension and answer the question of defining and calculating its area. The entire discussion is motivated by studying the expressions arising from super-BCFW recursion on tree-level, n-point NMHV amplitudes in the planar limit of N=4 Super Yang-Mills (SYM) theory. It has recently been discovered that such expressions should be interpreted as volumes of complex projective polytopes in some sense, and here we give this interpretation explicit meaning. In doing so, we uncover a novel calculus for calculating the volumes of such polytopes. This calculus can be used on the polytopes corresponding to these BCFW representations of amplitudes to obtain new expressions that make manifest all of the known properties of the polytopes. Additionally, we show how this new calculus can be used to readily obtain the volumes of any lower-dimensional face of an arbitrary polytope.
We begin by reviewing the known results for n-point NMHV amplitudes in planar N=4 SYM. In Chapter 2 we introduce our new definition of abstract (oriented) polytopes in terms of new objects called cyclic lists, and in Chapter 3 we define the volumes of these polytopes using cyclic lists in a natural way. Chapter 4 introduces a useful calculus for calculating not only the volumes of these polytopes, but also the volumes of any of their lower dimensional bounding polytopes. Finally, in Chapter 5, we briefly explore the twistor and cohomology theory that motivates the calculus and which may provide important insight for generalization of this whole discussion to more exotic spaces.
The role of the primate frontopolar cortex in mnemonic and choice behaviour
Keywords: frontopolar cortex
recency memory
anterior prefrontal cortex
WCST
episodic memory
social cognition

The role of the primate frontopolar cortex (FPC) has been investigated using human neuroimaging, lesion and disruption techniques. The results of these investigations have led to a variety of theories regarding the function of this region. It has been linked to the formation of task sets, the performance of multiple tasks, reasoning, context-specific memory (including episodic memory, prospective memory and source memory), attention to internally or externally generated information, mentalising and decision-making. It has not previously been possible to study this area using animal lesion techniques. Here, behavioural experiments conducted using non-human primates (rhesus macaque monkeys) who have received lesions to the frontal pole investigate the contribution of this region to context-specific memory, decision-making and social cognition. Functional magnetic resonance imaging (fMRI) is used to investigate changes in functional network connectivity which occur after lesions to this region. A long-lasting impairment is observed in contextual memory judgements (specifically, how recently a stimulus was encountered) after lesions to the frontal pole. An analysis of the influence of the outcomes of previous choices on behaviour on an analogue to the Wisconsin Card Sorting Test (WCST) indicate that monkeys with lesions to area 10 may be less influenced by the outcomes of an extended history of rewards than control animals. Long-lasting widespread disruption to functional networks after lesions to this region indicate that indirect anatomical connections from this region to posterior areas play a crucial role in the normal functioning of posterior networks.
Linear Paul trap design for high-fidelity, scalable quantum information processing
Keywords: quantum computing
quantum information processing
ion trap
Paul trap

We have designed and built a new linear Paul trap to expand our capability for carrying out high-fidelity quantum logic. We have identified some key limitations of our existing trap: the presence of a magnetic field gradient of 0.6 milligauss per micrometre, which limits the fidelity of Bell state preparation; a high axial micromotion amplitude, which limits the fidelity of operations on linear ion crystals; and a small numerical aperture in the imaging system, which restricts the collection efficiency and thus the performance of remote entanglement experiments.
We have carried out theoretical investigations into axial ion micromotion, including a full analysis of ion motion, using numerical simulations to understand the impact of electrode geometry. We have considered the effect of ion micromotion on the excitation spectrum, and how the micromotion sidebands can be used to selectively address ions within a linear crystal.
Based on this work, electrode design parameters have been selected for the new trap to prioritise sideband addressing while maintaining the most useful properties of the existing design. We have redesigned the mechanical structure of the trap, carefully considering manufacturing limitations, to minimise the magnetic field gradient, increase the numerical aperture to 0.6 and accurately align the electrodes. Additionally, we have considered methods of characterising the trap performance to assess how well the design criteria have been met.
Uncertainty, investment and capital accumulation: a structural econometric approach
Keywords: investment
structural estimation
uncertainty

This thesis contributes to the empirical literature about how uncertainty affects firm-level investment behavior and capital accumulation using a structural econometric approach. Chapter 2 surveys the literature and highlights that there are two key channels through which uncertainty may affect investment decisions. One reflects the non-linearity of operating profits in stochastic demand or productivity parameters, summarized as the Hartman-Abel-Caballero (HAC) effect. Another reflects frictions in capital adjustment, summarized by different forms of capital adjustment costs: partial irreversibility, a fixed cost of undertaking any investment and quadratic adjustment costs. Chapter 3 presents simulation evidence about the effects of uncertainty on investment dynamics and capital accumulation through different forms of adjustment costs. Using the Method of Simulated Moments, Chapters 4 and 5 estimate fully parametric structural investment models, for panels of Brazilian and UK manufacturing firms, respectively. Chapter 4 investigates the effects of reducing capital adjustment costs. Counterfactual simulations indicate that investment would be much more responsive to new information about profitability if firms in Brazil faced a lower level of adjustment costs. A lower level of adjustment costs would also induce firms to operate with substantially higher capital stocks. Both these effects are mainly due to the importance of the estimated quadratic adjustment costs. Chapter 5 then investigates the effects of changing the level of uncertainty. The estimated investment models predict a small effect of uncertainty on investment dynamics in the short-run, and a negative and potentially large effect of uncertainty on capital accumulation in the long-run. The long-run effect of uncertainty operates through the negative effect of quadratic adjustment costs in the baseline model, or through a richer combination of effects in an extended model that allows discount rates to vary with the level of uncertainty.
DNA damage responses to loss of telomere integrity
Keywords: CtIP
DNA damage response
BRCA1
Telomere integrity
EXO1

Linear genomes end in characteristic structures consisting of repetitive DNA and proteins: the telomeres. These play two critical roles: on one hand they avoid the of loss of genetic information due to the incomplete replication of the chromosome ends and on the other, they provide capping structures for chromosome termini, differentiating them from double strand breaks. Telomeres contain specialized proteins (the shelterin complex), as well as proteins present elsewhere on the chromosomes (chromatin remodelling, DNA damage repair and response factors). Interestingly, several DNA damage factors are required for proper telomere maintenance, drawing a thin line between telomere protection and their recognition as broken DNA ends.
Loss of telomere integrity has severe consequences for the cell, namely it can induce replicative senescence and cellular aging, or it can contribute to tumorigenesis. How telomeres are capped and how they are perceived by the cell when they become dysfunctional is essential for our understanding of the contribution of loss of telomere integrity to aging and disease. In order to unravel new factors involved in telomere maintenance, siRNA screens were performed. The optimization process has confirmed both telomeric foci and telomere dysfunction-induced foci (TIFs) as suitable readouts and the screens performed generated a list of potential candidate genes involved in telomere biology. Although some of the candidate genes tested in this work failed the validation process, other genes deserve further analysis.
In addition this work also studied the role of several DNA damage factors at uncapped telomeres. Furthermore, BRCA1, CtIP and EXO1 were found to be critical for the formation of end-to-end fusions generated after TRF2 inactivation. The requirement of this proteins in this process, suggests that not only that not only the classical non-homologous end joining (C-NHEJ) pathway is active at TRF2-depelted telomeres, but emphasises the multiplicity of mechanisms that act to repair dysfunctional telomeres.
Choosing to run: a history of gender and athletics in Kenya, c. 1940s - 1980s
Keywords: economic history
athletics
Kenya
gender
Africa
social history
sport
running

Choosing to Run: A History of Athletics and Gender in Kenya, c. 1940s – 1980s explores the history of gender and athletics in Kenya, with focus on the Rift Valley Province, from the onset of late colonial rule in the 1940s through the professionalisation of the sport during the last decades of the twentieth century.
The first two empirical chapters provide a history of athletics during the colonial period. The first highlights the continuity of ideas about sport and masculinity that were developed in nineteenth century Britain and were subsequently perpetuated by the men in charge of colonial sport in Kenya. The next chapter considers how pre-colonial divisions of labour and power within Rift Valley communities informed local peoples' cultures of running. The absence of women’s running was not only the result of sexism translated from the British metropole to its Kenyan colony but also of pre-existing divisions of responsibilities of indigenous Kenyan men and women into separate, gendered domains.
The second half of the thesis considers the impact of social change within women’s athletics internationally and of marriage, childbirth and education locally on female runners in the Rift Valley during the post-colonial period. Most women abandoned athletics once they reached maturity. Those who sought to do otherwise, as the final chapter argues, found that they could only do so by replicating the prototype of masculine runners that had already been established. Later, after the professionalisation of running allowed women to become wealthy, female patrons took this a step further by providing resources to those in their community in need, setting themselves up as 'Big (Wo)men'. This thesis uses athletics to reveal how gender relations and gender norms have evolved and the benefits and challenges that the sport has brought both to individual Kenyan women and their communities.
Analyses of functional sequence in mammalian and avian genomes
Keywords: bioinformatics
genomics
turnover
evolution
indel

The first draft sequence of the human genome was published over a decade ago, yet interpreting the functional importance of nucleotides in genomes is still an ongoing challenge. I took a comparative genomic approach to identify functional sequence using signatures of natural selection in DNA sequences. Mutations that are purged or propagated by selection mark sequences of significance for biological fitness. I developed and refined methods for estimating the quantity of sequence constrained with respect to insertions and deletions (indels) between two genome sequences, a quantity I termed αselIndel. This sequence is evolving more slowly than surrounding neutral sequence due to the purging of deleterious indel variants, and thus this sequence is likely to be functional. I estimated αselIndel between diverse mammalian and avian species pairs, and found a strong negative correlation between αselIndel and the divergence between the species’ genome sequences. This implies that functional sequence turns over rapidly as it is lost and gained over time. I quantified the variable levels of sequence constraint, and rates of sequence turnover, for different types of human biochemically annotated element. Furthermore, I found that similar rates of functional turnover have occurred across mammalian and avian evolution. Finally, I identified positively selected amino acid residues that may be important for Darwin’s finch beak development, and found evidence of adaptively evolving reproductive proteins in the ancestral songbird lineage. Collectively these results demonstrate the wide-spread nature of lineage-specific functional sequence with implications for understanding species traits and the use of model organisms to inform human biology.
Modelling embankment breaching due to overflow
Keywords: erosion
embankments
Navier-Stokes
breach
unsaturated soil
fluid dynamics

Correct modelling of embankment breach formation is essential for an accurate assessment of the associated flood risk. Modelling breach formation due to overflow requires a thorough understanding of the geotechnical processes in unsaturated soils as well as erosion processes under supercritical flow conditions. This thesis describes 1D slope stability analysis performed for unsaturated soils whose moisture content changes with time. The analysis performed shows that sediment-laden gravity flows play an important role in the erosion behaviour of embankments. The thesis also describes a practical, fast breach model based on a simplified description of the physical processes that can be used in modelling and decision support frameworks for flooding. To predict the breach hydrograph, the rapid model distinguishes between breach formation due to headcut erosion and surface erosion in the case of failure due to overflow. The model also predicts the breach hydrograph in the case of failure due to piping. The assumptions with respect to breach flow modelling are reviewed, and result in a new set of breadth-integrated Navier-Stokes equations, that account for wall shear stresses and a variable breadth geometry. The vertical 2D flow field described by the equations can be used to calculate accurately the stresses on the embankment during the early stages of breach formation. Pressure-correction methods are given for solving the 2D Navier-Stokes equations for a variable breadth, and good agreement is found when validating the flow model against analytical solutions.
Polyvinyl alcohol surface modification
Keywords: surface modification
pva
polyvinyl alcohol
pvoh

Poly(vinyl alcohol) (PVA) is a polymer used in numerous applications, principally those in which its high water solubility is a desirable asset. However there are also areas where PVA is limited by its inherent solubility (for example some specific environments in the biomedical field). This work has sought to overcome such limits by manipulating the surface of PVA in order to propose various means by which the surface solvent resistance might be increased while maintaining the bulk properties of the polymer. Both chemical and physical modifications have been tried and in each case progress has been made towards insolubilizing a single surface of the polymer when in film form.
Grafting various species onto the surface of PVA was successfully performed. It is believed that such species bonded to the PVA via attachment to the hydroxyl groups (though this has not been proven conclusively). The data contained herein has led to the conclusion that the primary factor in reducing solubility this way is the removal of the hydroxyl groups, and not the attachment of specifically highly hydrophobic molecules.
Introducing permanent cross-links into the surface region has been attempted via various routes. The data recorded shows promise however the system is far from optimised. The biggest challenge remaining is to optimise the depth of material cross-linked. Some steps have been made towards understanding and controlling this parameter though there is much scope for further investigation. The methods used have built on those used for bulk cross-linking and as such are new for the case of surface specific treatment.
An interesting phenomenon in some semi-crystalline polymers reported in recent years is that of surface specific crystallization. This effect has been successfully induced and observed in PVA to produce what is believed to be a highly crystalline surface layer, and crystalline regions of PVA are generally accepted to be more water resistant than amorphous ones.
In summary, in this work several surface-specific treatments for PVA have been trialled, providing options for post-film forming modification to reduce the surface water sensitivity whilst retaining the bulk properties of the polymer.
The Roman festival of the Lupercalia : history, myth, ritual and its Indo-European heritage
Keywords: Roman mythology
comparative mythology
rituals of initiation
Caesar
comparative religion
Vedic religion
Republican Roman religion
Lupercalia

The Roman festival of the Lupercalia is one of the most discussed issues in the field of pre-Christian Roman religion. Hardly a year goes by without an article on the subject appearing in a major Classics journal. But the festival presents a range of issues that individual articles cannot address. This thesis is an attempt to present a modern analysis of the phenomenon of the Lupercalia as a whole, including literary, archaeological and historical evidence on the subject.
The first section presents the ancient sources on the Lupercalia, and is divided into five chapters, each analysing a particular aspect of the festival: fertility, purification, the importance of the wolf and the foundation myth, the mythology of Arcadian origins, and Caesar's involvement with the Lupercalia of 44 BC. The second section places the Lupercalia in a wider context, discussing the festival's topography and the course of the running Luperci, its relationship to other lustration rituals, and its position in the Roman calendar, ending with an appraisal of the changes it underwent in late Antiquity. The third section employs methods from linguistics, anthropology and comparative religion to show that the Lupercalia involved a ritual of initiation, which was also reflected in the Roman foundation myth. The central chapter of this section discusses the methodology used in comparative Indo-European mythology, and offers a case study that parallels the god of the festival (Faunus) with Rudra of Vedic Hinduism. The last chapter considers other parallels with Indian religion, especially the relationship between flamen and brahmin. The thesis challenges a number of established theories on the subject and offers new evidence to show that the festival has Indo-European origins, but also that it played an important role throughout Roman history.
A study of the crystallographic, magnetic and electronic properties of selected ZrM2-H systems
Keywords: magnetism
metal-insulator transition
metal hydride

Dissolution of hydrogen into intermetallic compounds characteristically occurs at interstitial sites, causing little alteration to the base metal substructure but often bringing about substantial electronic and magnetic changes to the material. These hydrogen-induced alterations in the intermetallic hydrides are of interest both on a fundamental research level and in terms of technological applications; however, there exists no general theory as to how and why these alterations arise. The objective of this research is to elucidate to general effect of hydrogen on intermetallic compounds through the study of crystallographic, magnetic and electronic properties. An investigation has been carried out on the properties of three intermetallic compound - hydrogen systems of general formula ZrM₂, where M = V, Cr, Mn. All three compounds reversibly absorbed hydrogen with no change in crystal symmetry: powder diffraction studies showed that hydrogen was accommodated in interstitial sites of the existing metal sublattice via lattice expansion. The measurement of the magnetic properties of these systems was combined with the determination of conductivity and dielectric properties in order to describe the electronic e¤ects of hydrogen absorption. Despite the lack of signicant structural alteration in these systems, electron transfer between the metal sublattice and hydrogen may occur, as manifested in the appearance/disappearance of magnetic phenomena and the increase/decrease of electrical conductivity. Whilst the hydrogen addition in ZrM₂-H occurs simply via an expansion of the crystal structure, hydrogen does not act purely as null dilutant - there exist subtle electronic changes connected with the hydriding process as well.