VictorJuiz/thesis huggingface dataset:
A ketone ester for diabetes mellitus
Keywords: ketosis
ester
Beta-hydroxybutyrate
diabetes mellitus
ketone bodies

Various studies have reported that type 2 diabetes mellitus (T2DM) may be reversed by following a ketogenic diet, although it is not clear if this is due to carbohydrate restriction or a consequence of elevating the concentration of ketone bodies in the blood (ketosis). A recently developed ketone ester (KE) drink, which elevates human circulating D-βhydroxybutyrate (βHB) levels by ~3 mM within minutes, allows to isolate the effects of ketosis and carbohydrate restriction.
The aims of the work described in this thesis were to determine; if sustained exogenous ketosis is safe and well tolerated in healthy adults, L-Alanine’s contribution to the glucose-lowering effect of ketone bodies, the impact of acute ketosis on myocardial energetics and, if sustained ketosis is safe and tolerated in patients living with T2DM. In the first study (Chapter 3), twenty-four healthy adults (1:1 sex ratio, between 18 to 70 years old) drank 25 ml of the KE three times a day for 28 days. Anthropomorphic measurements, plus blood and urine biochemistry remained unaltered. All adverse effects of the KE were mild according to the participants.
In the experiments presented in Chapter 4, ten healthy adults fasted for 24 hours prior to the ingestion of 25 ml of the KE with or without 2gr of L-Alanine. Raising L-Alanine blood concentration attenuated the KE glucose-lowering effect by almost 50% (p<0.01). No significant differences in blood βHB, Free Fatty Acids (FFA), lactate and C-peptide were found when adding L-Alanine to the KE drink.
The work described in Chapter 5, involved twelve healthy adults who fasted for 24 hours and afterwards, drank 25 ml of the KE. Myocardial Phosphocreatine/Adenosine Triphosphate ratio (PCr/ATP) was measured before and 30 minutes after the KE drink using 31P Magnetic Resonance Spectroscopy at 7 Teslas. No significant differences in PCr/ATP were detected between measurements.
Finally, in Chapter 6, twenty-one type 2 diabetes patients, drank 25 ml of the KE three times a day for 28 days. Glycated haemoglobin (HbA1c) dropped from 7.7% to 7.2% and fructosamine concentrations from 335 to 290 µM. Overall time in the euglycemic range was assessed using continuous glucose monitors and improved by 2.3% (p < 0.01) while drinking the KE. Once again, anthropomorphic measurements, blood and urine biochemistry remained unaltered. All adverse effects of the KE were mild according to the participants and no events of ketoacidosis were documented.
In summary, the work described in this thesis has demonstrated; a close interaction between blood L-Alanine, ketone bodies and glucose concentrations and that a single KE drink has no effect on myocardial PCr/ATP in healthy participants. This work is the first to demonstrate, in the general population and in patients with T2DM, that sustained exogenous ketosis, is safe, well-tolerated, and may improve glucose control in T2DM.
Using positioning theory to understand marginalized students’ identities work and their learning experiences in English language arts classrooms
Keywords: English language arts classrooms
identity
marginalized students
culturally responsive teaching
marginalized
identity formation
English
identities
marginalised
Positioning Theory
discourse analysis

There are various dimensions of diversity that affect the learning experience of students. These might include aspects such as social background, ethnic and cultural origin, languages spoken, perceived learning ability, physical abilities, gender, sexuality, religion, and race. These work in dynamic ways and are influenced by both spatial and temporal social factors akin to general social transformations like globalization, migration, changing labour markets, and so forth. Whereas a lot of the social science literature in education has viewed these aspects of student identity and diversity as separate from each other, this qualitative, multi-modal study examines how these factors work intersectionally. As 16, 17, and 18-year-olds answer the question of who they are and explore the formative role that the learning environment—such as conversations they engage in and the texts they read—plays in identities development, this study uses a Discourse Analysis approach drawing upon Positioning Theory and Critical Incident Technique to analyse the discursive events around different social contexts across four Texas upper- secondary English Language Arts (ELA) classrooms. By analysing students’ dialogic interactions with their peers and their teacher, an interpretation of the agentic moves students make develops. The way in which these agentic actions affect learning experiences and the marginalizing forces that strengthen or diminish a student’s learning outcome also emerge. In thinking about how to treat students’ voices honourably, while reflexively focusing on my own positionality in relation to ethics, this study makes a positive contribution to both culturally responsive teaching and the field of education research.
Copper-catalysed autocatalytic reactions
Keywords: Autocatalysis
Origin of life
Self-reproduction
Out-of-equilibrium
Protocells

The work contained within this thesis describes the development and study of self-reproducing systems, created from simple chemical building blocks, that exhibit emergent, life-like properties. Several different autocatalytic systems that are driven by copper-catalysed azide-alkyne cycloaddition (CuAAC) reactions are reported.
Chapter 1 introduces the fundamental concepts relevant to the bottom-up construction of minimal living systems and highlights relevant synthetic advances in the field of systems chemistry. The following two chapters describe an autocatalytic system where surfactant formation from phase-separated components is linked to a CuAAC reaction.
In Chapter 2, the influence of product seed on the rate of the reaction and the impact of surfactant tail length on the kinetics of the reaction is investigated. Chapter 3 expands upon this system by exploiting the link between the secondary catalyst and the autocatalytic cycle to drive new reaction outcomes. A mechanistic model is formulated that rationalises the kinetic profiles based on the phase behaviour of the coupling partners and the catalyst.
Chapter 4 presents an out-of-equilibrium self-reproducing protocell system that models biological cells more faithfully. Selection and inhibition processes are observed between competing replicators and orthogonal downstream chemical reactivity is incorporated.
Chapter 5 describes the ongoing development of an asymmetric autocatalytic CuAAC reaction through formation of enantioenriched polytriazole ligands via dynamic kinetic resolution of allylic azides. An initial finding shows that this new class of chiral ligand induces chirality in asymmetric CuAAC reactions.
Finally, Chapter 6 offers concluding remarks and details future work that may improve upon the reported systems.
Studies of breakdown and pre-breakdown phenomena in high-gradient accelerating structures
Keywords: dislocation
linear accelerator
compact linear collider
CLIC
radiofrequency
fluctuation
dark current
vacuum breakdown
nucleation
RF
field emission
high gradient

Vacuum breakdown is a complex process and an important limiting factor of the performance of normal-conducting high-gradient particle accelerators, and can result in loss of luminosity in particle collider applications, as well as damage to accelerating structures. The work presented here was done in the context of the Compact Linear Collider (CLIC) study, but is also relevant to a variety of applications such as medical linear accelerators or high-electric-field vacuum electronics. The aspects of vacuum breakdown discussed in this thesis together provide the theoretical basis for important technological parameters for the design of normal-conducting high-gradient devices: the influence of radio-frequency design and material properties on the achievable field, and the mechanism of conditioning. The first part of this thesis discusses the development of an improved quantitative limit which determines the maximum accelerating gradient at which a given structure geometry could operate, with the intention of guiding the design of improved accelerating structures. It models the coupling of radio-frequency power to a breakdown, giving a value for surface electric field when loaded by a nascent breakdown. Calculations were performed on various cases that were tested experimentally, showing excellent consistency and the potential to become a very general model of vacuum breakdowns. The second part presents an experimental study of dislocation dynamics in copper surfaces subject to high electric fields, to better understand the mechanism of the nucleation of breakdowns. This is believed to involve stochastic deformation of microscopic features under high-electric-field stress. Field-emitted current from radio-frequency structures, as well as electrodes subject to a static electric field were precisely measured, revealing small fluctuations in the latter case. The dependence of the rate of events on the surface field and the distribution of time intervals between events was found to match prior theoretical predictions. The rate of fluctuations was also found to decrease with the cumulative number of voltage pulses applied, supporting the idea of work hardening due to stress from pulsed electric fields as a mechanism for conditioning.
Quantum master equations for spin chemistry
Keywords: Theoretical chemistry
Spin chemistry

It is a remarkable fact that the interactions between electron and nuclear spins, and their interactions with a magnetic field, can have a profound effect on chemical reactivity, despite the fact that the characteristic interaction energies are orders of magnitude smaller than thermal energy. These observations are explained by the existence of long-lived quantum coherences between spins in certain molecular species (in particular radical pairs), and the study of these spin effects constitutes the field of spin chemistry, a field which spans a wide range of systems, from biochemical reactions to device physics.
Because spin chemistry involves subtle quantum effects, many intuitive models used by Physical Chemists, in particular classical kinetic equations, cannot be universally applied. On the other hand, complete first principles modelling of reactions involving spin effects comes at an impossibly high computational cost in complex systems, and often offers little physical insight. In order to address the shortcomings of these approaches, quantum master equations (QMEs) are employed to describe spin chemical phenomena. These are equations that describe a reduced set of degrees of freedom quantum mechanically, accounting for the effects of remaining degrees freedom implicitly.
In this thesis I explore the use of QME techniques to resolve a range of problems in spin chemistry. These techniques can be used to obtain the correct radical pair spin QME, resolving questions about the role of quantum measurement in these systems. As well as aiding the development of the theory of spin chemistry, QMEs provide a practical tool for modelling radical pair reactions including spin relaxation effects, as I also demonstrate. As a final study of QME techniques in spin chemistry, I use these methods to show when the classical kinetic description of radical pair reactions is and is not valid.
The role of cerebellar GABA in visuomotor adaptation
Keywords: Functional Connectivity
Motor learning
Primary motor cortex
GABA
Magnetic Resonance Spectroscopy
Neurochemistry
Plasticity
Neuroimaging
Brain stimulation
Adaptation
Cerebellum
tDCS
Cortico-cerebellar connectivity
State-space modelling

In daily life we must constantly adapt our movements to changes in the environment or changes in our body. Adaptation is a fundamental property of the central nervous system and involves plastic changes across a network of brain regions, in particular in the cerebellum. These changes likely involve the major inhibitory neurotransmitter GABA. How cerebellar GABA changes during adaptation and how these changes are linked to behaviour is currently not well understood. By combining brain imaging (Magnetic Resonance Spectroscopy and Magnetic Resonance Imaging) and brain stimulation (transcranial direct current stimulation; tDCS) with computational modelling of behaviour, this thesis investigates the relationship between GABA, plasticity and motor adaptation.
First, the effects of stimulating the cerebellum with anodal tDCS were investigated. We found no effect of tDCS on adaptation, but an effect of session. We then studied the relationship between M1 GABA concentration and adaptation. We found that GABA concentration at baseline measured from left M1 hand area predicted retention of an adapted movement of the right hand. Next we investigated changes in functional connectivity elicited by adaptation. After performing an adaptation task, cerebellar resting-state functional connectivity was increased. Further, the change in a cerebellar network correlated with adaptation performance. Finally, we explored changes in cerebellar GABA during adaptation. During adaptation, cerebellar GABA decreased in the right compared to the left cerebellar hemisphere, controlling for GABA changes during movement execution.
This work provides first evidence that GABA decreases during adaptation in the right compared to the left cerebellar hemisphere. It strengthens the theory of cerebellar involvement in adaptation and suggests that cerebellar GABA plays an important role during adaptation. It also highlights the importance of M1 GABA in retaining the adaptive movement. Taken together, these results demonstrate a potential mechanism by which adaptation may be achieved in the cerebellum. In order to develop interventions that successfully and reliably enhance adaptation, it is crucial to understand the factors that influence these changes in the cerebellum and across the motor network.
Melioidosis in South-East Asia: contribution to a fever cohort, and in vitro studies of MAIT cell function
Keywords: gram-negative bacteria
fever
MAIT cell
sepsis
melioidosis
Burkholderia pseudomallei

Melioidosis is a neglected tropical disease caused by the Gram-negative bacterium Burkholderia pseudomallei (BP). Diabetes mellitus (DM) is a major risk factor. A mathematical model estimated 1,650,000 melioidosis cases in 2015 worldwide with 16,931 cases in Bangladesh, but the disease is rarely diagnosed in Bangladesh. This thesis set out to determine whether melioidosis is a significant cause of fever in Bangladesh, and to characterise the human mucosal-associated invariant T-cell (MAIT) response to BP and other Gram-negative bacteria.
We prospectively determined the aetiology of fever in 201 adult patients in Dhaka, Bangladesh, and found melioidosis to be the joint commonest cause (with E. coli) of bacteraemia. We also noticed high rates of antimicrobial resistance in Gram-negative infections.
We tracked the phenotype, activation and function of MAIT cells during acute melioidosis and other Gram-negative infections. MAIT cells responded rapidly to BP, releasing IFN-γ via both MR1 and cytokine-dependent pathways. The frequency and IFN-γ expression by MAIT cells following BP stimulation was significantly reduced in acute melioidosis patients compared to endemic controls, and significantly reduced in acute patients who died compared to survivors. We then examined the effect of DM on the MAIT cell response. In the endemic control population, IFN-γ expression was reduced in DM compared to non-DM. This was not explained by differences in activation or exhaustion markers (PD-1 and TIM-3) between groups. Finally, we found IFN-γ production by MAIT cells was significantly lower in the Gram-negative sepsis patients compared to healthy controls.
In conclusion, we have demonstrated that melioidosis is one of the commonest causes of community-acquired bacteraemia in Bangladesh. We have also revealed a potential key role for MAIT cells in survival in acute melioidosis, and their significance in host defence against other Gram-negative bacteria.
The neural representation of multisensory percepts: studying the integration of auditory and tactile stimuli in the somatosensory cortex
Keywords: behavioural neuroscience
two-photon imaging
vs1
audio-tactile integration
barrel cortex
neuroscience
multisensory integration
primary sensory cortex

Multisensory integration is the constant process through which we combine information across different sensory modalities in order to better interpret our environment. In early models of multisensory integration, primary sensory areas were thought to almost exclusively treat information from their preferred sensory modality and contribute little to the integration process. However, a growing literature now describes cross-modal responses in primary sensory cortices and direct cortico-cortical connections between primary sensory cortices. Therefore, cortical multisensory integration may begin as early as the primary sensory regions.
I built on this literature by examining how training on a multisensory integration task may alter vibrissal primary somatosensory cortex (vS1) responses to vibrotactile whisker stimulation and amplitude modulated pure tones. Unlike most previous studies, ours required the animal to identify a unique combination of vibrotactile and auditory stimulation in order to perform the task correctly. I used chronic in vivo two-photon imaging of vS1 to measure neural responses to stimuli throughout training on the Go/No-Go task. Responses of the same neural populations were compared prior to, during, and following task acquisition.
Mice learned to correctly identify specific combinations of audio-tactile stimulation. I observed vS1 responses to vibrotactile stimuli and found a subset of neurons that were responsive to sounds. I also found neurons that responded only to a single multisensory combination. Training led to an increase in the proportion of responsive neurons during acquisition on all tasks and a decrease in the proportion of responsive neurons after training on the multisensory task.
Most tracked neurons became either responsive or unresponsive during or after training. In contrast, very few neurons maintained constant response properties. While it remains unclear whether or how training may remodel local circuits, my findings suggest that training and experience lead to the recruitment of different populations of neurons in vS1 in a modality-specific manner.
Intensity modulated proton therapy in lung cancer
Keywords: monte carlo
lung cancer
intensity modulated proton therapy
pencil beam scanning
heart doses
IMPT
proton therapy

Proton beam therapy (PBT) has the potential to improve outcome in locally advanced non-small cell lung cancer (NSCLC). However, the technology associated with its delivery is still evolving. Treatment planning for PBT needs to account for various uncertainties to ensure accuracy of dose delivery. Multiple plan comparison studies have now shown that PBT is able to reduce dose to critical organs compared to photon therapy. However, dosimetric benefit does not necessarily translate to clinically meaningful outcome. The initial part of the thesis focused on the treatment planning aspect of intensity modulated proton therapy (IMPT) in conventionally fractionated radiotherapy for NSCLC. The subsequent parts that followed aimed at identifying patient groups where PBT is likely to be of highest clinical benefit. Therefore, the aims of this project were: [1] to evaluate and compare the robustness of IMPT and volumetric modulated arc therapy (VMAT) plans against setup uncertainties using the probabilistic scenarios method. [2] To evaluate the accuracy of the Raystation TPS analytical dose calculation (ADC) algorithm against Raystation Monte-Carlo (MC) algorithm. [3] To identify a sub-group of lung clinical cases where the Raystation TPS analytical algorithm may be clinically acceptable. [4] To identify a sub-group of patients who would benefit most from IMPT over VMAT with respect to cardiac sparing. The probabilistic analysis provides a fast and practical method for evaluating VMAT and IMPT plans sensitivity against setup uncertainty in locally advanced NSCLC. Although target robustness was achieved over the whole course of treatment, fraction doses were sub-optimal when plans were optimised based on the planning target volume. However, fraction VMAT and robust-optimised IMPT doses were comparable. In the presence of mediastinal involvement and absence of range shifters use of the Raystation ADC may be clinically acceptable for treatment planning in lung IMPT. Otherwise, the MC algorithm would be recommended to ensure accuracy of treatment plans. Finally, using the model-based approach, patients with both pre-existing heart disease and disease overlapping with or inferior to T7 vertebrae are likely to benefit most from proton over photon therapy to reduce risk of cardiac toxicity.
The multifarious muse: two palaeologan collections of paraenetic chapters
Keywords: Byzantine Poetry
Chapter Literature
Paraenetic Literature
Palaiologan Poetry

This thesis discusses the nature, genesis, authorship and audience of two paraenetic chapter collections of the Palaiologan period and offers a partial edition. I have called these collections Chapters in Four Ways (CFW) and Chapters in Political Verse (CPV). Their nature and composition are rather unusual in comparison to other chapter collections, and they are shrouded in an aura of mystery, which is made worse by the limited attention they have received from scholars. The study of these texts provides information on a wide range of topics such as the two main manuscripts, the genre of paraenetic poetry, the composition of CFW and CPV, intertextuality, hypertextuality, and the legacy of literary authorities in Byzantium, and the interaction between secular and monastic circles. It offers new insights on the authorship of the two collections, which this study shows to be closely related. The critical editions provided in this thesis make hitherto unedited texts available to the scholarly community, contribute to a better understanding of the two collections, and enrich our knowledge of late Byzantine literature.