VictorJuiz/thesis huggingface dataset:
The structural properties of DNA origami

In this thesis, we have investigated the suitability of using oxDNA to model DNA origami nanostructures. We used oxDNA to simulate a variety of DNA origami systems, then analysed the results to determine their key structural properties. Specifically, after introducing the area and outlining the procedure to simulate these systems, we report on three case studies that were based on experimental work; a theoretical project in which we designed an auxetic system based on knowledge gathered from the previous chapters, and a collaborative project with an experimental group looking into novel ‘barrel’ structures.
More specifically, the case studies we looked at were previously experimentally assembled DNA structures including a Möbius strip, six and twelve helix bundle kite structures that were connected with linkers of varying lengths, and ball structures containing six-way Holliday junctions. For these case studies, we found that oxDNA was able to replicate well existing experimental data, and therefore provide reliable insight into the subtleties of these systems that would be hard to elucidate using experimental techniques. As such, we were then able to design an auxetic-style system (in this case meaning a system which expands in two directions simultaneously) and predict its behaviour with confidence. Lastly, we assisted an experimental group by simulating and analysing a series of barrel structures to provide detailed information about these systems.
Looking to the future, we hope that the work outlined here will further encourage other groups, particularly experimental ones, to utilise oxDNA in their own work on DNA origami by both providing evidence of oxDNA’s utility, as well as sufficient guidance and assistance to get started.

Keywords: nanotechnology
dna origami
Advisor: Doye, J
Runtime protection of software programs against control- and data-oriented attacks

Software programs are everywhere and continue to create value for us at an incredible pace. But this comes at the cost of facing new risks as our well-being and the stability of societies become strongly dependent on their correctness. Even if the software loaded in the memory is considered legitimate or benign, this does not mean that the code will execute as expected at runtime. Software programs, particularly the ones developed in unsafe languages (e.g., C/C++), inevitably contain many memory bugs. Attackers exploiting these bugs can achieve malicious computations outside the original specification of the program by corrupting its control and data variables in the memory.
A potential solution to such runtime attacks must either ensure the integrity of those variables or check the validity of the values they hold. A complete version of the former method, which requires inspection of all memory accesses, can eliminate all the performance benefits of the language used. Alternatively, checking whether specific variables constitute a legitimate state is a non-trivial task that needs to handle state explosion and over-approximation issues. Regardless of the method preferred, most runtime protections are subject to common challenges. For example, as the scope of protection widens, such as the inclusion of data-oriented attacks (in addition to control-oriented attacks), performance costs inevitably increase as well. This is especially true for software-based methods that also suffer from weaker security guarantees. On the contrary, most hardware-based techniques promise better security and performance. But they face substantial deployment challenges without offering any solution to existing devices already out there.
In this thesis, we aim to tackle these research challenges by delivering multiple runtime protections in different settings. First, the thesis presents the design of a non-invasive hardware module that can enable attesting runtime correctness on critical embedded systems in real-time. Second, we address the performance burden of covering data-oriented attacks, by suggesting a novel technique to distinguish critical variables from those that are unlikely to be attacked. This is to develop a selective protection scheme with practical performance overheads, without having to check all data variables or corresponding memory accesses. Third, the thesis presents a software-based solution that promises hardware-level protection for critical variables. For this purpose, it leverages the CPU registers available in any architecture with extra help from cryptography. Lastly, we explore the use of runtime interactions with the operating system to identify malicious software executions.

Keywords: malware
software security
runtime integrity
memory safety
compiler
Advisor: Rasmussen, K
The dynamic landscape of cortical synaptic inhibition

Fast synaptic inhibition shapes cellular responses and network activity in the mammalian cortex. This inhibition is principally mediated by the activation of ionotropic GABA-A receptors (GABAARs), which are permeable to chloride (Cl-). For this reason, GABAAR function is intrinsically linked to processes that regulate the distribution of Cl- on either side of the neuronal membrane. Despite their fundamental role, the manner by which synaptic GABAARs function in the intact cortex has remained unknown. In this thesis, I explore how GABAAR-mediated synaptic signalling operates across different brain states and neuronal cell types in the mammalian cortex. To achieve this aim, I establish in vivo gramicidin perforated patch-clamp recordings, which enable me to study GABAAR function in the living rodent cortex, whilst preserving the integrity of the transmembrane Cl- gradient. By combining this method with pharmacological manipulations, I confirm that Cl- co-transporter proteins play a key role in establishing the equilibrium potential for GABAARs (EGABAAR) in vivo. I then use in vivo gramicidin perforated patch-clamp recording to reveal that GABAAR synaptic signalling is predominately shunting in the awake cortex. his results from relatively depolarised EGABAAR values, which arise due to the high levels of local network activity in the awake state. I further show that the animal’s sleep-wake history also contributes in setting EGABAAR in the awake cortex, consistent with evidence that sleep-wake history can modulate the activity of Cl- co-transporter proteins. To extend my studies into different neuronal cell types, I then establish a novel optogenetic method for probing intracellular Cl- regulation. By using a light-activated Cl- channel, I reveal differences in both the steady-state Cl- levels and Cl- extrusion capacities of two genetically-defined neuronal populations in the cortex, pyramidal neurons and parvalbumin-expressing interneurons. Taken together, the findings of this thesis support the idea that the ‘landscape’ within which GABAARs function is highly dynamic, depending on both the cortical state and neuronal cell type. This has important implications for how GABAAR function should be conceptualised within the cortex.

Keywords: optogenetics
cortex
ion dynamics
synaptic inhibition
electrophysiology
Advisor: Akerman, C
Sen, A
Quantum gates and Bose-Hubbard models with dipolar systems

Ultracold dipolar systems, featuring strong long-range dipole-dipole interactions, have been brought under increasing quantum control over recent years. In this thesis, we study the use of these properties for quantum information processing and simulation of many-body Bose-Hubbard models with off-site interactions. We first investigate robust entangling protocols for polar molecules, finding that shaped microwave pulses provide two-qubit entangling gates based on the dipole-dipole interaction with robustness to experimentally-relevant errors. We then numerically study the ground state properties of hard-core dipolar bosons confined in cylindrical optical lattices, where the curved lattice surface causes the anisotropic dipole-dipole interactions to vary around the ring of the cylinder. This expands the physics of analogous square lattice models due to the cooperation and competition of the interactions in different directions. Finally, we investigate the applicability of the lowest-band dipolar Bose-Hubbard model itself by comparing lattice and continuum methods for small systems of strongly interacting dipolar bosons in optical lattice potentials.

Keywords: matrix product states
magnetic atoms
optical lattices
polar molecules
quantum information
Advisor: Jaksch, D
Observability and predictability in quantum and post-quantum physics

I introduce a framework to distinguish two domains of physics - the manifest (i.e. the directly observable empirical records in terms of manifest configurations) and the non-manifest domain of physics (i.e. the things that the manifest configurations signify according to a physical theory). I show that many quantum 'paradoxes' rest on ambiguous reasoning about the two domains. More concretely, I study so-called 'surrealistic' trajectories, the 'delayed choice quantum eraser', and 'weak measurements'. Finally, I show how the alleged puzzles resolve in the framework provided.
I then formally define and address the question of whether quantum uncertainty could be fundamental or whether post-quantum theories could have predictive advantage whilst conforming to the Born rule on average. This notion of what I call 'empirical completeness' refers to actual prediction-making beyond the Born probabilities, and thus delineates the operational notion of predictability from a 'hidden variable' programme in quantum theory.
I study how empirical completeness connects to signal-locality, and argue that a partial proof for the impossibility of predictive advantage can be established for bi-partite quantum systems. The relevant results demonstrate signal-locality as a sufficient principle that might explain the fundamental chanciness in present and future quantum theories and, in turn, reconciles us to many quantum features as aspects of limits on Nature's predictability.

Keywords: quantum uncertainty
observability
quantum foundations
predictability
quantum measurements
surrealistic trajectories
non-locality
weak measurements
quantum paradoxes
empirical completeness
quantum erasure
hidden variables
determinism
post-quantum theories
pilot wave theory
quantum probabilities
Advisor: Timpson, C
Maroney, O
Cross-sectional analysis of FDG PET measured amygdala and parietal activity in patients with Alzheimer's disease and cognitive decline of unknown aetiology, for patients who may have limbic-predominant age-related TDP43 encephalopathy

Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently recognized cerebral proteinopathy that can lead to a clinical syndrome indistinguishable from Alzheimer’s disease (AD) in the antemortem setting.
Objective: To assess the prevalence and degree of amygdala hypometabolism in elderly patients referred to a tertiary hospital for assessment of cognitive decline.
Methods: Retrospective cross-sectional exploratory analysis (for the period of 2010 to 2022) of two cohorts (60 to70 years old [y.o] and 80y.o and above). All subjects’s data was retrieved from the Government of Western Australia Department of Health database, and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. A total of 348 subjects were used for this study. We used standard uptake values ratios (SUVRs) to to quantify metabolic activity in the amygdala and parietal lobe region. The normal range of metabolic activity for the amygdala and parietal lobe regions was generated by taking the mean SUVRs ±2 standard deviations from our Normal group (cognitively assessed normal subjects for their age). Subjects below the normal range of metabolic activity with only amygdala but not parietal lobe reduction formed our suspected LATE cases. Subjects with only parietal lobe reduction formed AD cases, and subjects with the both amygdala and parietal reduction formed our suspected comorbid AD /LATE cases.
Results: Suspected pure LATE, and comorbid AD/LATE in subjects with CDUA and AD is more common in age group 80 and over than in age group 60 to 70, with presence in respectively 7% and 6.3% of cases. Overall prevalence of amygdala reduction in AD subjects was approximately 18% in age group 80 and over, and 23.5% in age group 60 to 70, which is similar to what is suggested in the literature (approximately 20% LATE).
Conclusion: Results support using measured amygdala activity as a technique to further categorise CDUA and AD patients to determine suspected LATE status.

Keywords: FDG PET
FDGPET
FDG-PET
LATE
amygdala
AD
proteinopathy
TDP 43
Alzheimer’s disease
cognitive decline
parietal
Limbic-predominant age-related TDP-43 encephalopathy
TDP-43
Advisor: McCarthy, M
Smith, M
Development and assessment of a genetic and environmental risk model for colorectal cancer

Colorectal cancer (CRC) is the third most common cancer globally, and is readily prevented by screening. Colonoscopy is the gold standard screening tool but is invasive, expensive, and time consuming. ‘Risk-stratified’ approaches to screening, using genetic or non-genetic risk predictors to guide screening decisions, may improve screening outcomes and utilise limited resources more effectively.
The aim of this thesis was to develop and evaluate risk prediction models for CRC, to improve our ability to predict CRC risk. An initial search for novel genetic risk loci began with a new genome-wide association study (GWAS), following which meta-analysis of 5 new GWAS with 10 existing GWAS identified 31 new risk loci for CRC. Genome-wide linkage analysis combined with whole genome sequencing in two early-onset CRC families, and three families with multiple adenomas, identified several new possible risk loci for CRC including a potentially pathogenic variant in GFI-1.
Six polygenic risk scores (PRS) for CRC were then developed and tested in UK Biobank, with SNPs and weights derived from the GWAS meta-analysis. Evaluation of PRS performance showed that a genome-wide approach using LDpred2 software performed best, with a top age- and sex-adjusted C-statistic of 0.733 (95% confidence interval 0.710-0.753) in logistic regression. The PRS performed less well in women compared to men, and in minority ethnic UK Biobank participants.
Integrated genetic and non-genetic models were then developed, combining the top-performing PRS with the non-genetic QCancer-10 (Colorectal Cancer) model, which is based on primary care data. QCancer-10+PRS models modestly improved performance compared to QCancer-10 alone, with C-statistics of 0.730 (0.720-0.741) compared to 0.693 (0.682-0.704) respectively in men, and similar improvements in women. Decision curve analysis indicated small incremental improvements in net benefit, and the absolute difference in predicted 5-year risk was small (0.15-0.3%).
This thesis improves our understanding of the genetic basis of CRC risk, and risk prediction for CRC. Given the modest improvements in risk prediction with the addition of PRS to the QCancer-10 model, and the current logistical and ethical implications of PRS testing, there is no clear justification for PRS implementation in bowel cancer screening in their current form.

Keywords: risk prediction
colorectal cancer
polygenic risk score
Advisor: Wordsworth, S
Tomlinson, I
East, J
Hippisley-Cox, J
Essays in political economy

The following document outlines the research projects that I have conducted so far and would like to undertake in the upcoming academic year. The goal is to answer the following overreaching research questions:
What information is relevant to voters when it comes to getting information about malfeasance, and do voters update to 'informative' signals?
There has been a recent number of studies focusing on the relationship between information and accountability. Most recently, EGAP's Metaketa project has shown that information tends to have little or no effect on party preferences or voting behaviour. Several explanations have been proposed to understand these findings. Furthermore, there is significant discrepancy between survey experiments and field experiments. This research project would seek to contribute to the field by providing empirical evidence on the different stages of the information chain.
This thesis is structured as a three-papers work. Paper 1 is a field experiment conducted in cooperation with the Comptroller General Office (CGO) in Chile and the local NGO Chile Transparente during the municipal elections held in May 2021. This paper looks at whether voters update in response to information about malfeasance at their local government. The study was conducted just before the municipal elections in 116 out of 345 communes in Chile.
Paper 2 focuses on the importance of informational architecture and how it affects the way citizens assess the reliability and trustworthiness of the information provided. A key component of Bayesian belief updating is that the signals should be informative and provide digestible quantitative information. This paper seeks to explore this premise by using an innovative methodological approach. I conducted an adaptive design experiment, which has rarely been implemented in the field of political science and compare its results with those of a conventional static experiment.
Paper 3 is a methodological paper that aims to assess the reliability of a Randomised Item Response Technique (RIRT) to measure the prevalence of corrupt behaviour at the local level. This paper is mainly motivated to explore unobtrusive and relatively new indirect survey techniques to measure the prevalence of corrupt behaviour. The purpose of conducting this technique is to yield both population and individual-level measures of experienced-based corruption. I also provide evidence of bias-corrected estimates due to inattentiveness. For the viva, I report population and individual-level estimates obtained from the RIRT.

Keywords: experiments
corruption
accountability
indirect questioning techniques
Advisor: Duch, R
Ruiz, N
Matakos, K
Computational methods for the analysis of epigenomic activity in the human immune system

Epigenetics underpins the regulation of most genes, including many known to play a key role in the adaptive and innate immune system (AIIS). In this thesis, I developed a method called EpiNN that leverages epigenetic data to perform supervised gene classification with the goal of detecting AIIS-relevant regions of the genome. I trained EpiNN using a handcrafted list of genes with immune cell-specific epigenetic signatures and used it to scan the human genome for new AIIS-relevant regions. I detected 2,765 putative AIIS loci, of which 1,571 are uncharacterised by Gene Ontology (GO). I used stratified linkage disequilibrium (LD) score regression coupled with summary statistics from genome-wide association studies (GWAS) for 176 traits (average N=262k) to test whether the AIIS annotation is predictive of regional heritability for these traits. I detected significant heritability effects (average |τ∗| = 1.65, p < 0.05/176) for 20 out of 26 immune-relevant traits. In a meta-analysis of 63 independent heritable traits, immune-relevant traits and diseases were 4.45× (SE 0.09, p = 9 × 10−92) more enriched for heritability than other traits. The EpiNN annotation was also among the most significantly depleted in squared trans-ancestry genetic correlation in S-LDXR analysis of GWAS summary statistics from East Asian and European populations, indicating ancestry-specific effects. I analysed several of the predicted genes and found novel AIIS-specific enhancers and a novel AIIS-specific transcription start site in DNMT1, which was confirmed experimentally using PCR and Western Blot analyses. These results underscore the promise of leveraging supervised learning algorithms and large epigenetic data sets to detect genomic regions implicated in specific classes of heritable traits and diseases.

Advisor: Myers, S
Palamara, P
Nahkuri, S
The complexity of solution concepts in Lipschitz games

Nearly a decade ago, Azrieli and Shmaya introduced the class of λ-Lipschitz games in which every player’s payoff function is λ-Lipschitz with respect to the actions of the other players. They showed via the probabilistic method that n-player Lipschitz games with m strategies per player have pure 𝜖-approximate Nash equilibria, for 𝜖 ≥ λ√8n log(2mn). They left open, however, the question of how hard it is to find such an equilibrium. In this work, we develop an efficient reduction from more general games to Lipschitz games. We use this reduction to study both the query and computational complexity of algorithms finding λ-approximate pure Nash equilibria of λ-Lipschitz games and related classes.
We show a query lower bound exponential in nλ/𝜖 against randomized algorithms finding 𝜖- approximatepure Nash equilibria of n-player, λ-Lipschitz games. We additionally present the first PPAD-completeness result for finding pure Nash equilibria in a class of finite, non-Bayesian games (we show this for λ-Lipschitz polymatrix games for suitable pairs of values 𝜖 and λ) in which both the proof of PPAD-hardness and the proof of containment in PPAD require novel approaches (in fact, our approach implies containment in PPAD for any class of Lipschitz games in which payoffs from mixed-strategy profiles can be deterministically computed), and present a definition of “randomized PPAD”. We define and subsequently analyze the class of “Multi-Lipschitz games”, a generalization of Lipschitz games involving player-specific Lipschitz parameters in which the value of interest appears to be the average of the individual Lipschitz parameters. We discuss a dichotomy of the deterministic query complexity of finding 𝜖-approximate Nash equilibria of general games and, subsequently, a query lower bound for λ-Lipschitz games in which any non-trivial value of 𝜖 requires exponentially-many queries to achieve. We examine which parts of this extend to the concepts of approximate correlated and coarse correlated equilibria, and in the process generalize the edge-isoperimetric inequalities to generalizations of the hypercube. Finally, we improve the block update algorithm presented by Goldberg and Marmolejo to break the potential boundary of a 0.75-approximation factor, presenting a randomized algorithm achieving a 0.7368-approximate Nash equilibrium making polynomially-many profile queries of an n-player 1/n−1 -Lipschitz game with an unbounded number of actions.

Keywords: PPAD
Lipschitz games
Computational complexity
Query complexity
Advisor: Goldberg, P
Santhanam, R