VictorJuiz/thesis huggingface dataset:
Template-directed synthesis of supramolecular heterometallated nanorings

This thesis presents the synthesis, characterization and study of a range of heterometallated porphyrin nanorings. These studies revealed some fascinating electronic and supramolecular properties.
Chapter 1 summarizes some of the work done in the Anderson group on porphyrin nanostructures and reviews the literature regarding template-directed synthesis.
Chapter 2 describes the discovery of the novel technique “shadow mask templates”. We show that oligopyridine ligands can be used to dictate the sites of demetallation when a magnesium porphyrin nanoring is treated with acid. Magnesium centers that are coordinated to the template are protected whereas uncoordinated magnesium centers are removed. After site‐selective demetallation, the template can be removed, and other cations, such as zinc(II), copper(II), and silver(II) can be inserted into the free‐base porphyrin centers. This strategy provides a simple route to a wide range of heterometallated porphyrin arrays.
Chapter 3 describes the investigation of quantum interference phenomena in bis copper and bis-silver six-porphyrin nanorings by EPR spectroscopy via measurement of the exchange coupling between the paramagnetic centers. Using orientationally selective DEER and RIDME, we investigate how various factors affect the exchange coupling between two spin centers in a porphyrin nanoring.
Chapter 4 describes the thermodynamic and kinetic investigation of complexes where two oligopyridine templates stack on top of each other inside porphyrin nanorings. Using UV/vis/NIR titrations and kinetic 1H NMR experiments, it was found that in a 12-porphyrin nanoring where there is space for the templates to bend, there is high positive allosteric cooperativity. In a 6-porphyrin nanoring where the templates are more constrained, there is negative cooperativity. In the case of the negatively cooperative systems, there is a high kinetic barrier for exchange of templates and reaching equilibrium can take up to several weeks.
Chapter 5 describes how stacked templates can be used in a novel type of Vernier template-directed synthesis because they fit a favorable conformation of the targeted complex and does not require the complex to twist. This turns out to be a significant advantage when synthesizing complexes with sterically bulky solubilizing groups, and is the most efficient method to prepare a 12-porphyrin nanoring with THS-solubilizing groups.

Keywords: Porphyrins
Template-Directed Synthesis
Supramolecular Chemistry
Quantum Interference
Advisor: Anderson, H
Semiclassical transition state theory for chemical reactions: theory, development and applications

Semiclassical Transition State Theory (SCTST) is an efficient rate theory, which aims to calculate the rate constants of chemical reactions, including quantum tunnelling effects, without requiring a global potential energy surface. It has applications in understanding chemical reactions involving medium sized molecules where more computationally expensive methods are not possible. The work in this thesis aims to increase our understanding of the theory, apply the method to interesting problems in chemistry, and develop the method for the study of a broader range of systems and problems.
The Theory section of this thesis begins with a review of the theoretical basis of SCTST. We then illustrate how the theory can be adapted for treating complex systems with internal rotational degrees of freedom, and higher orders of perturbation theory. We then show that the SCTST method implicitly accounts for key multidimensional effects, such as corner-cutting and variational effects, and identify the limitations of this approach.
In the Applications section, we apply SCTST to the study of a range of chemical problems. We show that SCTST in full and reduced dimensions can be used to help understand the decay of Criegee intermediates in the atmosphere, and identify a water-catalysed route that contributes significantly to the decay process. By studying enol-formation from a phenyl pyruvic acid derivative, we provide evidence for an alternative reaction mechanism, consistent with recently performed experiments.
In the Development section, efforts to adapt the method to increase its range of applicability are then described. A reduced dimensional form of SCTST is discussed and shown to be particularly efficient, where the required number of electronic structure calculations is reduced to an absolute minimum. We also show how the SCTST rate equations can be recast to calculate tunnelling splittings in chemical systems in a reliable and cost efficient way.
Finally, we present a user friendly code base for SCTST calculations, made freely available for download, called pySCTST.

Advisor: Clary, D
Design, development, characterisation and operation of ATLAS ITk strip staves

ATLAS (A Toroidal LHC ApparatuS) is a general purpose particle physics experiment designed to exploit the physics potential of the Large Hadron Collider. Two further upgrades are planned to increase the luminosity of the LHC, the latter of which ("Phase 2" scheduled for 2023/2026) will give rise to the High Luminosity Large Hadron Collider (HL-LHC). With peak luminosity increased by a factor of 3.75 beyond today's values, a new Inner Tracker (ITk) will be required for ATLAS. An all-silicon design is chosen with a mixture of Pixel and Strip layers.
This thesis documents the electronic system design of the ITk Strip Staves to be used in the barrel region, and presents results from tests of front-end chips, modules and staves built using prototype chipsets made in the same 130 nm technology as will be used in the experiment. Most of the results come from systems using the first of these chipsets, HCC130 / ABC130, but the final chapter documents wafer screening and single chip results using a later prototype chipset, HCCStar / ABCStar, which has a revised front-end amplifier design and an updated data transfer topology which makes greater use of the available bandwidth. Although beyond the scope of this thesis, the first staves built with the latter chipset have recently been completed. The HCCStar and ABCStar designs are presently being reworked to give improved tolerance to Single Event Effects (SEE), leading toward the assembly of the first pre-production staves later this year. The production phase is due to start next year with commissioning of the completed system, in the ATLAS cavern, scheduled to take place in 2025.

Keywords: Silicon Microstrips
ITk Strip Staves
ATLAS ITk Strip Detector
Front-End Electronics
Advisor: Weidberg, A
Ecstasy or justice? The sexual author and the law, 1855-1885

John Addington Symonds (1840-1893) was a British poet, critic and biographer who wrote what may be the first manifesto in English calling for legal equality for homosexual men, "A Problem in Modern Ethics: Being an Inquiry into the Phenomenon of Sexual Inversion, Addressed Especially to Medical Psychologists and Jurists" (1895). "Ecstasy or Justice? The Sexual Author and the Law, 1855-1885," explores Symonds' work in the context of his epistolary relationship with the American poet Walt Whitman, whose influential 1860 edition of "Leaves of Grass," with its frank treatment of homoerotic themes, inspired a generation of British writers, feminists and activists, in addition to provoking Symonds himself into more direct, though textually veiled and coded, engagement with homoerotic themes. "Ecstasy or Justice? The Sexual Author and the Law, 1855-1885," also examines the impacts of laws criminalizing publications with sexual themes, and laws criminalizing same-sex offences, as background for analysis of certain texts by Symonds' contemporaries, including Algernon Charles Swinburne, Dante Gabriel and William Michael Rossetti, Christina Rossetti, the painter Simeon Solomon, the activists for women's rights Josephine Butler and Annie Besant, and later, the young Oscar Wilde. The thesis addresses ways in which these "sexual dissidents'' work may show certain impacts of pressure from the passage of the Obscene Publications Act and other laws managing privacy and speech in Britain in the 19th century. It also makes the case that pressures of this kind on literary texts in Britain may have affected outcomes for writers such as Whitman eventually in the United States as well, as the passage of the Comstock Act in 1873 led to comparable restrictions on literary freedoms for American writers, and helped lead to the withdrawal of a print run of "Leaves of Grass." The thesis argues that we can't fully assess the work of many writers in Britain after 1857 and in America after 1873, without taking into account the possible impacts on literary texts of restrictions on freedoms of speech and on private sexuality.

Keywords: John Addington Symonds
Advisor: Evangelista, SM
Addressing syntactic privacy for privacy-preserving data analysis and data release

Existing approaches to tackle the challenges of privacy-preserving data analysis and data release are subject to vulnerabilities from certain attacks (which is the case for syntactic privacy models) or suffer in terms of efficiency, scalability or utility (which is the case for techniques based on secure multi-party computation). In addition, definitions of privacy (or any associated properties and notions) remain open to different interpretations among various stakeholders due to privacy’s multi-dimensional and multi-faceted nature. In such environments, individuals who are not necessarily privacy experts, such as software developers or system designers, may struggle to select an appropriate privacy model or mechanism to protect their systems. This dissertation presents simplifications, analyses, considerations and promotions in the context of privacy-preserving data analysis and data release to support utility, flexibility and privacy.
As a first step, we facilitate understanding, application and analysis of syntactic privacy notions via abstraction to games. Via these games, we clarify understanding of, and relationships between, different privacy notions. Further, we give an unambiguous understanding of adversarial actions.
We analyse previously defined privacy games with regards to their applicability and relationships to each other, and define policies to support predominantly non- experts to establish an overview and to select the ‘fitting’ privacy notion / game for their applications. In this context, we utilise our game-based definitions to analyse and reason about privacy properties in a content-based clustering recommendation system as well as a collaborative-filtering based classification recommender system.
The second part is focused on the application to practice. Important in this context is the specification of requirements, which we derive from an analysis of multiple real world applications. Our use cases are predominately placed in distributed multi-party settings, where data remains split between mutually distrustful parties.
Given these real world constraints, we adapt and investigate a novel approach (based on trusted computing techniques) that remains resilient to many implementation-specific vulnerabilities, and increases efficiency and scalability. Our investigation comprises an advanced threat analysis covering high-level privacy model attacks to low-level side-channel vulnerabilities; furthermore, we present benchmarking results illustrating the superiority in performance of our approach compared to existing solutions.
Overall, we aim to foster understanding of privacy and applicability in data analysis and data release applications.

Keywords: privacy-preserving data mining
privacy
Trustworthy Remote Entity
privacy-preserving data analysis
Software Guard Extensions
SGX
differential privacy
MPC
multi-party computation
TRE
privacy games
Advisor: Simpson, A
Prediction and inference of dynamics in quantum plasmas

Quantum plasmas arise in a range of physical contexts, from planetary interiors to Inertial Confinement Fusion experiments. We require sophisticated numerical approaches to find the structural and dynamic properties of these complex, many-body quantum systems; diverse in accuracy and applicability, these computational approaches each have their own strengths and (often ignored) weaknesses. By combining existing techniques with newly developed algorithms, this thesis addresses some weaknesses that are common to many state-of-the-art calculation methods for quantum plasmas, and opens up paths to calculating properties that were not previously accessible. The focus of the thesis is a method based on Bohmian mechanics for dynamic structure calculations; alongside this, stochastic gradient Markov Chain Monte Carlo methods are developed for inferring plasma properties from experimental data.

Keywords: Stochastic Calculus
Bohmian Mechanics
Warm Dense Matter
Markov Chain Monte Carlo
Plasma Physics
Quantum Plasmas
Advisor: Gregori, G
Ketone metabolism in the heart

The aphorism “fat burns in the flame of carbohydrate” leads to the question of whether the oxidation of the ketone body, D-β-hydroxybutyrate (βHB), is facilitated by anaplerosis via glycogen and/or glucogenic amino acids. The work in this thesis aimed to investigate the importance of anaplerosis in ketone body metabolism in the isolated heart. The first study (Chapter 3) determined whether glycolysis from glycogen affected the heart’s ability to oxidise βHB. The glycogen content of isolated rat hearts was altered by perfusion with or without glucose, before perfusing with Krebs-Henseleit (KH) buffer containing [14C]-βHB or [5-3H]-glucose to measure βHB oxidation and glycolytic rates, respectively. βHB oxidation in hearts with low glycogen (LG) was 2-fold lower than those with high glycogen (HG), and βHB oxidation rates directly correlated with glycogen content. βHB oxidation decreased glycolytic rates to ~0.2 μmol. gww-1.min-1 in all hearts, redirecting glucose into glycogen in LG heart, but not in HG hearts. βHB alone or with glucose increased the Krebs cycle intermediates, citrate, 2-oxoglutarate and succinate, and the total nicotinamide adenine dinucleotide phosphate (NADP/H) pool measured using metabolomics. Thus, glycogen is required for βHB oxidation. The second study (Chapter 4) determined the effect of βHB oxidation on cardiac energetics using 31P-NMR spectroscopy. In HG hearts, βHB oxidation increased the free energy of ATP hydrolysis (∆GATP) by increasing the concentration of phosphocreatine ([PCr]) and the phosphorylation potential, calculated from the [ATP]/[ADP][Pi] ratio. βHB oxidation was unable to increase the low ∆GATP in LG hearts due to low glycolytic flux through pyruvate. The third study (Chapter 5) defined the effect of the glucogenic amino acids, asparagine, valine and glutamine, on βHB oxidation in hearts with decreased flux through pyruvate to oxaloacetate (glycogen-depleted and perfused with low glucose buffer). Asparagine increased βHB oxidation 2-fold by increasing the metabolites of the malate-aspartate shuttle and purine nucleotide cycle, aspartate, fumarate and guanosine triphosphate. Neither valine nor glutamine increased βHB oxidation rates. The final study (Chapter 6) determined the effect of substrates and loading conditions on cardiac efficiency (the ratio between hydraulic work and oxygen consumption) in working rat hearts. Fatty acids were found to decrease cardiac efficiency, via increased oxygen consumption and decreased hydraulic work, at both low and high pre- and afterloads. At high, but not at low, pre- and after-loads, βHB plus acetoacetate (AcAc) increased efficiency by increasing hydraulic work. Thus, βHB plus AcAc increased cardiac efficiency more than glucose alone or with fatty acids at high pre- and after-loads. In conclusion, βHB oxidation and glycolysis from glycogen have a synergistic relationship in heart, which serves to increase the ∆GATP and thereby cardiac efficiency.

Keywords: metabolomics
glycolysis
glycogen
redox states
D-β-hydroxybutyrate oxidation
Advisor: Evans, R
Clarke, K
Cyclic amine functionalisation by engineered cytochrome P450BM3

Cytochrome P450 enzymes are known for their characteristic activity of C–H bond oxy-functionalisation whereby one oxygen atom of atmospheric dioxygen is inserted in an available carbon-hydrogen bond of their substrates, such as drugs and natural products, to form the alcohol derivative. Cytochrome P450BM3 from Bacillus megaterium has been extensively engineered to develop biocatalytic pathways to bioactive compounds due to its self-sufficiency, high expression level and promiscuity in substrate recognition. In this thesis, a high proportion of available carbon-hydrogen bonds in cyclic amines and lactams have been shown to be oxidised by engineered P450BM3 variants with high turnover and reasonable regioselectivity (Figure 1). A combination of substrate engineering via introducing substituents (methoxy and methyl), N-protecting groups (phenyl, benzyl, acyl, Boc, mesyl, tosyl, and isopropylsulfonyl) and auxiliary carbocycles (cyclopentane and cycloheptane), and protein engineering by site-directed and site-saturation mutagenesis at active site residues identified by screening with a 48 P450BM3 variant library of diverse substrate pocket topology and polarity, have enabled the oxidative diversification of these core motifs in numerous FDA-approved drugs. Unusual activities of P450BM3 – the Povarov reaction with N-phenyl cyclic amines and N1-C8' coupling (amination) of 6-methoxy-1,2,3,4-tetrahydroquinoline – were also discovered. Biotransformation in vivo and in vitro of these substrates reached 1 g/L/day with 20 mM substrate conversion at turnover numbers of up to 15,000. The research has provided the basis for developing alternative routes to hydroxy and multi-functionalised cyclic amines and lactams, introducing synthetic handles for functional group elaborations of such compounds which are frequently used in fragment-based drug discovery.

Keywords: C-H activation at non-activated carbons
CYP102A1
cytochrome P450
amine functionalisation
protein engineering
Advisor: Wong, L
On adaptive behaviour and its neural basis: Insights from computational models and the mouse auditory cortex

The processes of learning and decision making are at the core of intelligence. Although these phenomena have been studied for centuries, their nature and bi- ological implementation are still unclear. In this thesis, I approach these issues from multiple perspectives. First, I developed a novel infrastructure for performing large-scale behavioural and optogenetics experiments in rodents. Additionally, I performed validating experiments showing that auditory cortex is necessary for sound detection in mice.
To gain further insights into mouse behaviour, I developed a novel model of head-fixed mouse behaviour. I applied this model to data from mice performing a sound detection task and showed that it accurately describes behaviour. Addition- ally, I used this method to obtain a deeper understanding of behavioural strategies. Next, I extended this model to account for changing strategies over learning and demonstrated that it is able to infer changing strategies on a trial-by-trial basis. By applying it to behavioural learning data, I showed that mice exploit simplicity in task-structure to rapidly acquire an effective behavioural strategy.
Finally, I investigated the neural basis of sound-driven behavioural strategies by performing two-photon calcium imaging in layer 2/3 of the mouse auditory cortex during behaviour. Neuronal activity, which covaried with environmental events, importantly covaried with behavioural choice, potentially reflecting its role in driving behaviour. Modelling of population activity showed that choice-related activity is best accounted for by both changes in population gain and local func- tional connectivity. These data suggest that local computations in layer 2/3 of mouse auditory cortex contribute to sound-driven behaviour.
Together, this work has generated novel tools and represents an almost end- to-end study of the processes of learning and decision making, providing a deeper understanding of behaviour and its neural basis.

Keywords: neuroscience
auditory neuroscience
learning
perceptual decision making
Advisor: Dahmen, J
What is the potential role of veterinary vaccination in the control of Rift Valley fever in Kenya?

Rift Valley fever virus (RVFV) is a zoonotic arbovirus that causes fever, high mortality in young and spontaneous abortions in livestock species. It can have a dramatic impact on livestock health and production as well as on public health and people’s livelihoods. The licensed veterinary vaccines have multiple issues including residual virulence, which underlies their contraindication for use in pregnant animals, the need for high containment facilities for their manufacture and diagnostic tests are unable to differentiate between infected and vaccinated animals (DIVA).
The literature indicated that RVF seroprevalence across the African continent was significantly higher in small ruminants during outbreaks than interepidemic periods (IEPs), suggesting these populations are often naïve when an outbreak occurs. The serosurvey conducted in three Kenyan counties found that RVF seroprevalence was recorded in at-risk areas during IEPs, suggesting silent circulation.
A non-inferiority trial was conducted comparing a promising candidate vaccine, ChAdOx1 RVF, with the commercialised Smithburn vaccine in multiple target livestock species (n=613) under natural environment conditions. The successful conduct of the trial in accordance with veterinary GCP has been underpinned by engagement and collaborations with regulatory authorities and trial monitoring teams across multiple sites in Kenya and abroad. The primary endpoint for the trial was to assess non-inferiority of the ChAdOx1 RVF vaccine compared to the Smithburn vaccine with regards to seroconversion as measured by an RVF virus neutralising antibody assay (FRNT). These seroconversion results were utilised in the development of a transmission dynamics model.
The ChAdOx1 RVF vaccine was found to be safe, DIVA compliant and non-inferior in all species. Vaccine scenarios suggested vaccinating with ChAdOx1 RVF in the dry season annually or every 3 years would decrease cumulative incidence of infected livestock significantly. These results show ChAdOx1 RVF is a promising candidate for registration and use in livestock in areas of risk for RVF.

Advisor: Warimwe, G
Gubbins, S
Ewer, K