VictorJuiz/thesis huggingface dataset:
Hydrogen bonding phase-transfer catalysis with alkali metal fluorides: enantioselective synthesis of β-fluoroamines from reaction development to scale-up
Keywords: beta-fluoroamines
Enantioselective fluorination with alkali metal fluorides
hydrogen bonding phase-transfer catalysis

This thesis reports the development of hydrogen bonding phase-transfer catalysis (HB PTC) for asymmetric fluorination with alkali metal fluorides. This catalytic manifold harnesses the ability of fluoride to engage in hydrogen bonding to promote solubilisation of the inorganic fluoride salt, with concomitant formation of a reactive chiral catalyst fluoride complex. Herein, HB-PTC has been applied to the synthesis of enantioenriched β fluoroamines, with a focus on the industrial application of the methodology.
Chapter 1 introduces the challenges associated with enantioselective nucleophilic fluorination with alkali metal fluorides and the strategies reported in the literature for fluoride activation. An overview of properties and applications of β-fluoroamines is also included. Chapter 2 opens with a summary of the previous work on HB-PTC. Next, the chapter is devoted to describing the development of the asymmetric synthesis of β fluoroamines with KF and CsF via HB-PTC. Computational modelling is used to rationalise the observed selectivity and scope. Chapter 3 describes the development of a practical and scalable (> 10 g) synthesis of the novel N-alkyl bis-urea introduced in Chapter 2. Different synthetic routes are explored, and advantages and drawbacks of each are compared. Chapter 4 reports the study of the scale up (200 g) of the enantioselective fluorination in a mechanically stirred 1 L reactor, representing the proof of principle that HB PTC can be applied in industrial settings. Thermal safety tests and preliminary calculations on the mixing requirements are included. The chapter concludes with the analysis of the recyclability of the catalyst and of its degradation products. Chapter 5 contains additional screening tables, synthetic procedures, and characterisation data from compounds of Chapters 2‒4.
Continuities and discontinuities in covert operations to interfere in democratic votes of succession
Keywords: Foreign Policy
Russia
Politics
Interference
Intelligence
Elections

In the international system, states have historically carried out covert operations to interfere in the votes of succession of foreign democracies. In the 20th century, such operations relied upon physical tools; more recently, they have relied upon digital ones. This thesis asks, why and how has the practice of covert interference in democratic votes of succession evolved in the digital age? In investigating this question, this thesis examines three cases of covert operations to interfere in democratic votes of succession, in Italy in 1948, in West Germany in 1972, and in the United States in 2016. This thesis then structures its cross-case analysis around identifying continuities and discontinuities across these operations. Based on this three-pronged small-N study, I argue that core features of covert operations to interfere in democratic votes of succession have remained constant over time, but that the reach and the penetrability of the internet have enabled states to engage in such operations with greater efficiency than was possible in the pre-digital era. The findings of this thesis hold significance for any democracy seeking to defend its electoral processes in the digital age. The continuities identified herein reveal the timeless methods of interfering actors, while the discontinuities reveal what about these operations have changed amid the spread of the internet and why democracies have become more exposed to external penetration in the process. More fundamentally, this thesis offers a roadmap for understanding covert interference in democratic votes of succession as a distinct and evolving phenomenon in international relations with which democracies will continue to grapple.
Women, gender, and society in late Antiquity: a study in visual culture
Keywords: gender
archaeology
visual culture
late antiquity
women

This thesis uses visual culture to build a more nuanced understanding of the experiences of ordinary women in Late Antiquity and the impact of gender on their everyday lives. While much scholarship has examined women and gender in this period through literary sources, such texts provide almost exclusively elite male perspectives. In this thesis, I instead centre the representation of normal women in visual culture, from their donor portraits and funerary images to depictions on jewellery and graffiti. Analysis of this underexplored evidence allows me to undertake new evaluations of key themes such as education and family life, and to examine previously unrecognised aspects of women’s experience. Throughout the thesis I integrate diverse textual sources into my analysis, from literary and legal texts to documentary papyri, inscriptions, and letters, where possible highlighting texts composed by women. By taking such an holistic approach I am able to demonstrate how attention to material and visual culture can corroborate, challenge, and complicate traditional textual histories.
The thesis is divided into an introduction, conclusion, and four main body chapters which examine the cultivation of beauty through the toilet, the popularity of depicting women as learned, the vicissitudes of female experience through the life course, and opportunities for women to engage with their communities as donors. Through these analyses I show that ordinary women were involved in late antique society to a far greater degree than is allowed for in texts, from changes in urban life and elite display to new forms of civic patronage. Christianity emerges repeatedly as a factor driving change in women’s intellectual and public lives, as do transformations in governance and administration. At other times a marked continuity with earlier centuries is demonstrated where we would expect significant change, such as in the roles of widows and virgins. I also question several of the methods we use to study ancient lives, in particular with regard to definitions of education and learnedness, arguing for greater flexibility in order to adequately study women and non-elite groups. My thesis also demonstrates the importance of women’s homosocial relationships, both in informal social situations and the more formal segregation of the monastery.
Crustal strain and seismic hazard of the NE Tibetan Plateau
Keywords: Seismology
Active Tectonics
Interseismic Strain
Remote Sensing
InSAR
Drone
Tibetan Plateau
Continental Earthquakes
Hexi Corridor
Historical Seismograms
Geomorphology
Seismic Hazard
1920 Haiyuan Earthquake
Pleiades

This thesis focuses on the seismic hazard of the NE Tibetan Plateau, an area that hosted one of the largest and most deadly earthquakes in China’s recorded his- tory. In order to estimate rates of earthquake occurrence from strain rates, it is necessary to use the Gutenberg-Richter relationship and assume a maximum magnitude. The largest recorded earthquake in the NE Tibetan Plateau is the 1920 Haiyuan Earthquake. It has often been quoted as of M 8.7, on a magnitude scale of uncertain meaning, a result of unknown origin and an outlier in empirical magnitude and rupture parameter relationships. Therefore, I first use historical seismograms, modern Pleiades imagery and field-acquired drone data to re-estimate the magnitude of the 1920 Haiyuan Earthquake, which is corrected to MW 7.9±0.2. Literature re- view suggests the possibility that many magnitudes of historical Chinese earthquakes based on the intensity and magnitude scaling relationships could be systematically overestimated. An existing conversion method is highlighted for quick magnitude re- estimations for historical earthquakes, though careful systematic revisits to historical earthquake magnitudes are recommended. Second, 10 ascending and 13 descending frames of Sentinel-1 interferometric synthetic aperture radar (InSAR) data acquired between 2014 to 2019 and covering the NE Tibetan Plateau are analysed to determine crustal velocities in the satellite line of sight. These frame-based line-of-sight velocities are combined with constraints from Global Navigation Satellite System (GNSS) velocities to derive a high-resolution 3-dimensional velocity field for the region in a well-defined frame of reference. The crustal velocities can be used to constrain geodetic slip rates across the Haiyuan, Gulang and East Kunlun Faults, creep time series over the Laohushan Section of the Haiyuan fault, as well as enabling the determination of crustal strain rates that can be used to determine the rates of earthquake occurrence for the region.
Structure for algorithms, graph reconstruction and hypercube intersections
Keywords: intersection patterns
partial deck
graph reconstruction
connected greedy edge colouring
asymptotic dimension
small cards
structural graph theory
hypercube
algorithms

We begin by studying several structural properties of graphs that lead to 'efficient' colouring algorithms. We first show that the treedepth of a Pt-free graph is bounded by t times its maximum degree, and use this to show that the number of 3-colourings can be computed in time O(2√tn log(n)) for any Pt-free graph on n vertices. We then prove that several graph classes, including the class of planar graphs, have asymptotic dimension 2. This has applications to graph colouring and partitioning schemes. We end this part by studying when a 'connected' greedy procedure for colouring the edges of a graph can find an optimal colouring.
In the second part, we consider extremal questions on the reconstruction of graph parameters. The deck of cards of a graph G is given by the multiset {G-v:v ∈ V(G)} of induced subgraphs of order n-1. A graph parameter f can be reconstructed if any two graphs G and H with the same deck of cards satisfy f(G)=f(H). For n sufficiently large, we show that the number of edges of a graph on n vertices is determined by any subdeck containing at least n- 1/12 √n cards. For planar graphs, we can reconstruct not only the number of edges, but also the degree sequence, even if a linear number of cards is missing. We then turn our attention to a set-up where rather than missing cards from the deck, the cards are 'smaller', and we consider the problem of reconstructing the degree sequence and recognising connectivity. In all cases, we significantly improve the best-known bounds.
Finally, we turn to the study of intersection patterns in the hypercube. We investigate the possible intersection sizes a k-dimensional linear subspace can have with the hypercube {0,1}n. For fixed k and arbitrary n, the intersection size must be between 1 and 2k. We exactly determine the possible intersection sizes larger than 2k-1 for every n, settling a conjecture of Melo and Winter, and then disprove a second conjecture of Melo and Winter by showing that a positive proportion of the intersection sizes smaller than 2k-1 are impossible to obtain. After that, we give some partial progress towards the problem of determining the minimum number of hyperplanes required to cover a subset B⊆{0,1}n without covering any point from {0,1}n \ B.
Deep learning approaches for pre-clinical drug discovery
Keywords: compound design
machine learning
drug discovery
virtual screening
deep learning

Deep learning methods have experienced a revolution, driven by their successful application in fields such as computer vision and natural language processing. In this thesis, we describe several novel methodologies leveraging deep learning for applications to pre-clinical drug discovery.
First, we propose a generative approach to the design of molecular linkers which incorporates basic 3D information. In large-scale tests, we find that our method substantially outperforms a database-based approach, the previous de facto approach for this problem. Through a series of case studies, we demonstrate the application of our approach to scaffold hopping, fragment linking and PROTAC design. We then extend this framework to incorporate physically meaningful 3D structural information, providing a richer prior for the generative process, and also apply our method to molecular elaboration tasks, such as R-group design.
We then turn our attention to predictive modelling, in particular structure-based virtual screening. We find that the advances in convolutional neural networks (CNNs) for general computer vision tasks are applicable to structure based virtual screening. In addition, we propose two techniques to incorporate domain-specific knowledge into this framework. First, we show that limitations in docking necessitate the use of multi-pose scoring and demonstrate the benefits of an average scoring policy. Second, we propose a transfer learning approach to construct protein family specific models, utilising knowledge of the differences between protein families.
Finally, we investigate how a generative approach can be used to improve the training and benchmarks sets employed in structure-based virtual screening. We propose a deep learning method that generates decoys to a user’s preferred specification in order to control decoy bias or construct sets with a defined bias. We show that our approach significantly reduces the bias contained in such sets. We validate that our generated molecules are more challenging for docking-based approaches to separate from bioactive compounds than previous decoys. In addition, we show that CNN-based structure-based virtual screening methods can be trained on such compounds.
Modelling the mechanisms of microsilica particle formation and growth
Keywords: combustion
particle nucleation
asymptotic analysis
reaction-diffusion system
mathematical modelling
silicon furnace
particle growth
silica fume
microsilica
moment equations
mixing layer

Microsilica particles arise as a byproduct of silicon furnace operation, created inside high temperature flames due to the combustion reaction of silicon monoxide with oxygen. These nanoparticles, which grow as silicon dioxide vapour condenses on the surface of existing particles, are used in a variety of composite materials. The size and quality of the particles affect the performance of the material used for such applications, and hence control of these quantities is of importance to manufacturers.
Motivated by this, we derive a mathematical model that connects local fluid flow, thermal and chemical conditions of the furnace to the formation and growth of microsilica particles. Since the regions where microsilica particles form are local to a very thin reaction zone, we focus on the dynamics within the flame front. We first study two distinct reductions of the model: the case of initially well-mixed or spatially homogeneous chemical species, and the case of initially separated chemical species. In the latter case, the one-dimensional domain is given by a cross section of the reaction zone and diffusion plays a dominant role in providing material to a combustion front. In order to incorporate fluid flow, we extend the previous work to 2-D by considering a mixing layer approach, that is, by assuming two parallel flows entering the domain with distinct velocities, temperatures, and concentrations. We study how the mixing layer evolves as both streams interact, and how mixing affects the formation and growth of particles. In all cases, we provide asymptotic approximations under various limits and neglecting the effect of the particles on the chemicals and temperature, and numerical solutions of the full model. Our results suggest that oxygen availability and a sufficiently high temperature are essential for the combustion reactions to occur, strongly influencing the width of the reaction zone and the particle size distribution. Furthermore, when the flow is almost uniform, fewer particles form and more of the total mass corresponds to large particles, in contrast with the non-uniform case.
British commerce and Spanish government in New Granada in the early 18th century, from the asiento to the War of Jenkins' Ear
Keywords: new granada
south sea company
war of jenkins' ear
spanish colonial history
contraband

This dissertation presents a case study of the economic confrontation that eventually led to the War of Jenkins’ Ear between England and Spain in the early 18th century. It discussed the commercial competition taking place in New Granada in the years leading to the conflict, as exemplified by the experience of the South Sea Company factory in the port city of Cartagena, its efforts to penetrate the colonial market, and Spain’s response to this challenge.
While several studies have examined the issue before from a purely English, or purely Spanish perspective, this dissertation presented the two efforts as experienced by the colonial society of New Granada. The dissertation relied on both Spanish and English archival sources, allowing for a more comprehensive view of the complex economic, political and social exchanges taking place in New Granada at the time between the two powers. It also adds to the knowledge about a not very thoroughly-studied period of the economic history of New Granada, by documenting in detail the operations of the South Sea Company factory, the first organised English commercial settlement in the country.
The experiences of the South Sea Company in New Granada from 1713 to 1739 and its interaction with Spanish authorities and merchants there, showed both the limitations of English power against what was still strong Spanish administrative and military control over the South American mainland, as well as the English commercial vitality that was rightfully seen by Spain as a threat to the continuity of its empire there. While the focus of the study is to show how this rivalry was carried out in the local sphere of New Granada’s colonial society, it also provides elements for a wider view on the divergent imperial experiences of England and Spain.
Atlas of the hole/house of dementia: the escutcheon, the hearth and the floor-cloth as motifs for dwelling and storytelling
Keywords: Cultural Dementia
Dementia
Exhibition making
Vernacular Architecture
Storytelling
Installation Art
Imagination
Mnemonics

This thesis presents a set of reflections in object and textual form on some questions of dwelling, memory and the experience of movement within architectural space. The research builds upon an older tradition of investigation into the phenomena of remembering and forgetting in the pre-enlightenment world. The exhibition is structured around the three figures of the escutcheon, the floor-cloth, and the hearth. Each of these figures opens up particular ways of moving between and around elements of a dwelling.
The methods and structures developed in this thesis respond to memory and the idea of the childhood home. These configure into mnemonic devices which are comparable to those rooted within the texts of the architect and theorist Juhani Pallasmaa and certain images that appear in Italo Calvino and Jorge Luis Borges. The research proposes that the human brain learns faster through analogy, that human cognition is wrapped within narrative and motion such as are inscribed on the mind and can easily be revisited. The objects, diagrams, paintings and installations contain a rich iconography of shapes and structures that prompt partial memory of real dwelling spaces. The textual component of some 15000 words follows the practice of the objects themselves in providing fragmented journeys through incomplete and misremembered spaces.
At the end of each chapter appear images of an ongoing architectural project for a sunglasses distributor in Spain that I have been undertaking during the period of this research, with all the pragmatic compromises and contradictions that this involves. The invitation offered to the viewer/reader is that those stresses that appear within the structures described in the thesis should be embraced in favour of the proposals it implicitly rejects.
Investigating the regulation of ACC1 activity in pancreatic beta cells
Keywords: diabetes
insulin
beta cells
metabloism

Aims:
Acetyl-coA Carboxylase 1 (ACC1) is an enzyme that couples glucose metabolism with de novo lipid synthesis in lipogenic tissues, by converting acetyl-CoA to malonyl-CoA. In beta cells, ACC1 plays a critical role in beta cell growth and insulin secretion . However, very little is known about how ACC1 activity is regulated in beta cells. The aims of the current project were to 1) assess the role of the AMP-activated protein kinase phospho-site serine 79 (ACC1S79) in beta cell function and whole body glucose homeostasis; and 2) screen for novel phospho-sites that may regulate ACC1 activity in beta cells.
Methods:
(i) To investigate the functional role of the ACC1S79 phospho-site in beta cell function, we studied a mouse model with ACC1S79 mutated to alanine (ACC1S79A), which were obtained by crossing ACC1 double knock-in mice 2 with wild type mice to isolate the ACC1S79A point mutation. We assessed glucose homeostasis in vivo and insulin secretion from primary islets.
(ii) We purified the ACC1 protein from transformed INS1 beta cells following culture with different glucose concentrations, and performed quantitative unbiased phosphoproteomics to characterise ACC1 phospho-sites. Mass spectrometry (LC-MS/MS) was performed using a Q- Exactive MS, mascot searches run against the Uniprot data base, and data analysed using MaxQuant and Perseus. We generated phospho-specific antibodies against key phospho-sites identified that exhibited a dynamic response to glucose stimulation, and used western blotting to investigate these sites further.
Results:
(i) Female ACC1S79A mice exhibited normal glucose homeostasis, whilst males showed lower fasting blood glucose, and a modest reduction in blood glucose during glucose and insulin tolerance tests compared to wild type littermate controls. No significant differences in fasted or glucose-stimulated serum insulin levels were found between the genotypes in vivo. Likewise, there was no significant change in insulin secretion from isolated ACC1S79A islets at baseline (2 mmol/l glucose) or in response to glucose-stimulation (7.5 and 20 mmol/l glucose).
(ii) Using quantitative phosphoproteomics, we identified twenty phospho-sites on the ACC1 protein in beta cells. ACC1S1215 was highly-phosphorylated at 2 mmol/l glucose, and showed a marked and highly significant reduction in phosphorylation in response to 15 mmol/l glucose, in contrast to the more modest changes in phosphorylation of ACC1S79. In contrast, phosphorylation of ACC1S25 and ACC1S49 was lower at basal glucose and increased upon glucose stimulation. Validation by western blotting confirmed that ACC1S1215 phosphorylation was highly-regulated by glucose, with ACC1S79 phosphorylation more subtle.
Conclusions:
Our data demonstrate that phosphorylation of ACC1S79 does not play a major role in insulin secretion in vivo or ex vivo. However, other phospho-sites identified by our phosphoproteomic screen may play a role in regulating ACC1 activity in beta cell and other ACC1-expressing tissues.