VictorJuiz/thesis huggingface dataset:
Algorithmic explanations: to become a mockingbird

As algorithms are increasingly used to make potentially life-altering decisions the importance of ensuring they meet certain standards of fairness, accountability, and transparency is becoming paramount. Complex models that are poorly understood are susceptible to bias, reliance on protected or irrelevant features, and adversarial examples. This concern has spawned interest in explainable and interpretable algorithms which allow humans to understand algorithmic decisions. Running parallel to this issue is an increasing reliance on algorithmically generated profiles to target advertisements online. Often these profiles are built on sensitive characteristics, without user knowledge or means of recourse. They can influence user perceptions of self, alter the content users are exposed to, and reveal to other parties characteristics which users have chosen not to share. This project aims to increase user autonomy and privacy online by leveraging techniques in explainable machine learning.
This work begins by creating a prototype tool called Mockingbird that builds more than twenty algorithmically generated profiles based on Twitter data. These profiles are created using various techniques, including lexicons, neural networks, and Gaussian Processes. Mockingbird offers explanations for most of these profiles, primarily using a post-hoc explanatory tool. Finally, using synonym suggestions and techniques used to generate adversarial examples, Mockingbird gives users suggestions on how to alter their tweets in order to change their algorithmic profiles. Mockingbird is novel in combining profiles, explanations, and tools to change algorithmic profiles.
The system was tested through several (n = 6) lab experiments to gauge user response to explanations and willingness to alter their data. It appears that users are generally not concerned about their algorithmic profiles when used for advertising, but would be much more concerned in higher stakes applications. Users were also unwilling to change their existing data to control algorithmically generated profiles, viewing the necessary changes as too disruptive to how they use social media. This work points to avenues of further research focusing explicitly on editing social media data to influence high stakes decisions such as job, visa, and loan applications.

Keywords: algorithmic profiles
explainable machine learning
transparency
Advisor: Van Kleek, M
Derogation and the scope of the jus cogens norm in the jus ad bellum

It is widely accepted that there is a jus cogens norm in the jus ad bellum. Yet uncertainty exists as to its scope, due to the existence of two exceptions to the prohibition on the use of force: self-defence and force authorised under the UN Charter. This dissertation aims to identify the jus cogens norm in the jus ad bellum by clarifying the meaning of ‘derogation’ in the context of jus cogens norms. In doing so, this dissertation addresses three questions: 1) what does it mean to say that a norm permits no derogation?; 2) do exceptions derogate from jus cogens norms?; and 3) how do the exceptions to the prohibition on the use of force affect the scope of the jus cogens norm in the jus ad bellum?
A jus cogens norm is identified as a norm of general international law ‘accepted and recognised by the international community of States as a whole as a norm from which no derogation is permitted’. Yet scholars understand ‘derogation’ in different ways: a ‘narrow’ view understands derogations as attempts to contract out of the jus cogens norm inter se, while a ‘broad’ view understands derogations as any norm that makes conduct inconsistent with the jus cogens norm lawful. On the broad view, there can be no exceptions to jus cogens norms.
It is argued that to say a norm permits no derogation means that there can be no lawful conduct inconsistent with obligations arising under that norm. As a result, any apparent ‘exceptions’ to jus cogens norms must be limitations on the scope of that norm. Thus, neither force lawfully authorised under the Charter nor force lawfully used in self-defence is prohibited by the jus cogens norm in the jus ad bellum. Such uses of force are defined and regulated by non-jus cogens norms, which are recognised by the jus cogens norm without forming part of it.

Keywords: Jus cogens
Derogation
Automated feature selection for survival analysis with deep learning

Survival analysis has attracted the development of new deep learning models, most notably the recent state-of-the-art model DeepHit for competing risks. However, in real-world medical settings with many features and insufficient data, deep learning models can suffer from severe performance deficits.
In this dissertation, we propose robust changes to DeepHit’s architecture and training procedure to counter this problem. Furthermore, we develop several methods to improve DeepHit’s performance through novel approaches to automatic feature selection in deep survival analysis. We propose both filter and hybrid methods for hard feature selection, as well as neural network architecture adaptations that achieve soft feature selection.
Despite only sparse literature around feature selection for deep neural networks, and little previous evidence for its benefits, our experiments on two medical datasets demonstrate that substantial performance improvements against the original DeepHit model are achievable.

Advisor: van der Schaar, M
Understanding substrate recruitment by BTB-Kelch family E3 ligases

Over 600 E3 ligases are identified that covalently modify substrates with ubiquitin to control their degradation, trafficking or activity. Many are linked to human diseases and represent an important class of drug targets. An understanding of their substrate recruitment mechanisms is necessary to elucidate their functions and to enable drug design. BTB-Kelch proteins are the substrate adaptors for a large family of Cullin3-dependent E3 ligases that remain incompletely characterised. Recurrent mutations in the Kelch domain of KBTBD4 act as an oncogenic driver of medulloblastoma. I identified specific substrates of KBTBD4 mutants using mass spectrometry-based proteomics. These data suggest a novel gain-of-function mechanism for these tumour mutations. For other targets with known substrates, I performed SPOTs peptide arrays and biophysical analyses to map their binding motifs (degrons) and was able to solve the crystal structures for the substrate complexes of the E3 ligases KLHL20, KLHL12 and KLHL3 with substrates DAPK1, DVL1 and WNK3, respectively. The mapped ‘LPDLV’ motif in DAPK1 and ‘PGGPP’ motif in DVL were observed to insert into the central pockets of the Kelch domains to form hydrophobic interactions, whereas the WNK3 interface was more polar with WNK3 Thr541 forming a potential phosphorylation site to regulate salt homeostasis.
I further used the DAPK1 degron peptide to develop an Alphascreen assay for compound screening and identified the first low micromolar inhibitors of KLHL20 with potential application in cancer, as well as Alzheimer’s disease. I also established a panel of 17 human Kelch proteins for future work leading to a new structure of KLHL17 as well as a selectivity panel that revealed the high selectivity of known inhibitors of KEAP1. These results confirm the diverse structural characteristics of the Kelch domains observed from my work. Overall, these features help to explain how E3 substrate adaptors can perform their diverse roles in protein regulation.

Advisor: Bullock, A
D'angiolella, V
X-ray diffraction studies of laser-shocked crystals

When materials are shock compressed, they undergo changes in microstructure that act to relieve the large shear stresses associated with the compression. The plasticity mechanisms that mediate this transition such as slip and twinning remain poorly understood, especially in the case of polycrystals, which make up the majority of real world materials. This work presents a theoretical outline for analysing Debye-Scherrer diffraction experiments under large strains. A method is demonstrated to measure both the components of strain in the normal and transverse directions, as well as crystal orientation using highly textured samples. These theoretical predictions are compared with simulated diffraction patterns from molecular dynamics simulations. This technique is applied to two different experiments on tantalum. The first provides a measurement of the timescale for plastic deformation, which we find similar to comparable experiments in copper, while the second provides the first in situ of observation of twinning in shock compressed metal.

Advisor: Wark, J
Targeting GPR84: a receptor involved in regulating inflammation

GPR84 is a G protein-coupled receptor that is activated by medium-chain fatty acids and is highly expressed in macrophages, suggesting a role for dietary fatty acids in the regulation of inflammatory responses. The validation of GPR84 as a therapeutic target has been hindered by the structural homogeneity and poor selectivity of available chemical tools, and the consequent poor understanding of GPR84 physiology. The aim of this thesis was to develop structurally novel GPR84 agonists that may reveal new aspects of GPR84 biology.
A ligand-based virtual screening approach was used to identify a compound active in recombinant cell cAMP assays that represents a new scaffold of GPR84 agonist. The compound was chemically optimised and extensively characterised for potency, stability, solubility, and selectivity, resulting in DL-175 which shows properties appropriate for an in vitro chemical probe. Furthermore, unlike previously reported GPR84 ligands, DL-175 is inactive in beta-arrestin recruitment assays, showing a marked bias for G protein signalling pathways.
In primary murine bone marrow-derived macrophages (BMDMs), DL-175 induced dosedependent responses in impedance signalling assays that were absent in GPR84-/- BMDMs. Moreover, the BMDM response to DL-175 was significantly more sustained than that induced by range of publishedGPR84 agonists, indicative of biased signalling in disease-relevant primary cells. The functional consequences of biased agonism at GPR84 in immune cells were investigated by a direct comparison between DL-175 and widely used GPR84 agonist 6-OAU. Both agonists enhance U937macrophage phagocytosis, but have strikingly different abilities to promote chemotaxis in the same cells. This work demonstrates that biased agonism enables the selective activation of functional responses in immune cells and delivers a high-quality chemical probe for further investigation.

Advisor: Russell, A
Greaves, D
Applications of Raman spectroscopy and fluorescence spectrometry in glioma surgery and neuropathology

The diagnosis and management of patients with diffuse gliomas presents a significant challenge due to the aggressive nature of these tumours. Currently, there is no cure, and therefore the aim of treatment is to prolong survival and maintain quality of life for as long as possible. Surgical resection is an important part of the treatment, with evidence that increasing the extent of tumour resection results in prolonged survival, but the intraoperative identification of tumour boundaries is difficult. Techniques such as fluorescence-guided surgery have been shown to increase the extent of resection. The molecular genetic classification of gliomas, particularly identification of isocitrate dehydrogenase mutation and 1p/19q-codeletion, has also been shown to be critical for clinical and surgical decision-making.
Raman spectroscopy probes the unique molecular vibrations of a sample in order to accurately characterise its molecular composition. No sample processing is required, allowing for rapid analysis of tissue. The first aim of this project was to apply Raman spectroscopy to intraoperative and neuropathology analysis of gliomas both in terms of genetic subtyping and identification of the tumour/normal tissue boundary. Ex vivo Raman analysis of fresh tissue samples, from 62 patients collected straight from surgery, demonstrated 79%-94% sensitivity and 90-100% specificity for predicting the three most common glioma genetic subtypes. Raman spectroscopy was also compared with intraoperative visual fluorescence and was found to be significantly better at identifying tumour at the tumour boundary compared to the gold standard of visual fluorescence.
The second aim of the project was to develop a fluorescence spectrometry laboratory setup to allow for testing of enhanced fluorescence visualisation methods. Here, a laboratory-based fluorescence setup was correlated with the intraoperative light sources. A stable fluorescence standard was proposed and developed, using a laser dye, and was correlated with the intraoperative fluorescence. This experimental setup was used to prove the hypothesis that the operative endoscope is more sensitive at detecting visual fluorescence than the operative microscope.

Advisor: Vallance, C
Ansorge, O
Plaha, P
Force and possibility: a study in the theory of reasons

This thesis is a study in the theory of reasons. In the main, it comprises three chapters that investigate a single question from different angles, namely, the question of what it is that makes reasons possible.
In Chapter 1, I propose a theory of what makes reasons possible. The theory progresses by defending a version of the thesis that ought implies can against an argument by John Gardner. What emerges from this defence is a formal model of possibility for facts that qualify as reasons for action. This contributes a new analytical test to the existing literature on normativity in respect of the question of what it is for a fact to be a reason.
In Chapter 2, I take up the question of whether legal rules are possible reasons for action. They are, indeed, commonly regarded in this way. Yet are such rules reasons for action themselves (the reflexivity thesis) or is a statement of a rule a way of paraphrasing reasons that we may already have (the paraphrastic thesis)? I argue for a version of the paraphrastic thesis.
In Chapter 3, I examine an influential methodology in the philosophy of law that underpins some influential theories on how legal rules can be possible reasons for action. I focus specifically on conceptual analysis as the methodology behind the requirement of compliance in Joseph Raz’s theory of mandatory norms. This requirement holds that if such norms are to be reasons, then they must allow for the possibility that one can do as a reason requires one to do because it requires one to do it. I argue against this view, holding that the requirement is impossible on methodological grounds.
What unifies the chapters of this thesis is a concern for what makes reasons possible. The take-home message is threefold. First, not all possible facts are possible reasons (Chapter 1). Second, legal rules are not themselves possible reasons (Chapter 2). And third, if we misuse the methods of conceptual analysis, we will end up with impossible reasons on our hands (Chapter 3). My tactic is to begin broadly by examining facts as possible reasons, then narrow down to one kind of reasons, namely, legal ones, and then step back to diagnose one source of impossible reasons.

Keywords: normativity
reasons
Advisor: Endicott, T
Dynamics underlying Plasmodium vivax mitochondrial genome diversity across the Eastern Hemisphere

Plasmodium vivax (Pv) malaria is a human infecting blood parasite distributed widely across both tropical and temperate regions. In order to increase the understanding of past dynamics influencing its current distribution, this thesis explores its origins, spread and evolutionary past through diversity and evolution of the mitochondrial genome. Exploring several different factors that would have affected its dispersal, including mosquito vector species and geographic distance, the main focus of Chapter 2 is on understanding when and with which past human migrations it spread across the continents of the Eastern Hemisphere. A special emphasis on the Melanesian region is included in Chapter 3, which shows considerable diversity in human populations and cultures, and has high incidence of all four species of human infecting malarias (P. vivax, P. falciparum, P. malariae, P. ovale). Although previous publications indicated an especially high level of diversity in Pv mitochondrial genomes in Melanesia; in this study it is shown to be a sampling artefact due to denser sampling. In both chapters a novel cross-disciplinary data comparison is undertaken, matching Pv mitochondrial genome phylogeny and population genetics with modern human mitochondrial genome data, human and hominid archaeological data, archaeological data from human commensal species and phylogenetic data from human associated diseases. Results indicate that not only the current Melanesian Pv but also the Pv strains found across the Asian continent to the east of India were likely introduced by the first wave of anatomically modern humans (Homo sapiens) to leave Africa. The strong patterning seen across this eastern region has ostensibly been shaped not only by relatively stable human populations for the last several thousand years, but is also associated with a strong regional heterogeneity of mosquito vector species and clades. In contrast, the present study confirms previously observed homology in Pv mitochondrial genetics from India to the west. Presumably the homology is due to increased human population movement and contact between the western regions, as well as greater overlap in mosquito vector species across the region, as shown in this study. Even so, with the addition of data from new sites across the western half of the Eastern Hemisphere, including samples from central and western Asia, there is a detection of low levels of population diversity. Lastly, Chapter 4 gives an overview of the applications of different genetic markers used in malaria research over time, reviewing the continued value of using mitochondrial DNA, on its own and in combination with other available genetic data – in an age of whole genome sequencing.

Keywords: historic epidemiology
phylogenetics
human migration
global distribution
vector disease
mitochondrial
malaria
Advisor: Bogaard, A
Mueller, I
Barry, A
A comparative study of homelessness and services to meet basic needs

People experiencing homelessness often have difficulty accessing resources to meet their basic needs for food and sanitation. However, services to meet basic needs—such as public toilets, soup runs, and day centres—have been under-explored in research concerning homelessness and the welfare state. Accordingly, relatively little is known about the ways in which these services fit into the extension of rights through the welfare state. This research examines evidence from policy documents as well as the perspectives of service providers, city government officials, and advocacy groups to investigate the following question: In what ways, if any, does the relative salience of social or civil rights in a welfare state affect the provision of services to meet the basic needs of people experiencing homelessness? Through a comparative analysis of New York and London, two major cities within the ‘liberal’ welfare regime, this study demonstrates that the provision of services to meet basic needs is fragmented, in both cases consisting of a mix of government, voluntary, and private provision. Additionally, the relative salience of social and civil rights affects the ways in which policymakers and service providers conceptualise poverty and need, as well as the claims advocacy groups make on behalf of people experiencing homelessness. Drawing from concepts in social citizenship and social exclusion, the analysis shows that these findings reflect differences in understandings of poverty, rights, and responsibilities in each city.

Keywords: homelessness
social services
social policy
sanitation
Aristophanes and the poetics of surprise

The purpose of this thesis is to examine the variety, the mechanisms, and the poetological intention of the effect of surprise in Aristophanic comedy, addressing the phenomenon not as a self-evident or unselfconscious element of comedy as a genre, but as an elaborate system which characterises the style of the specific dramatist. More precisely, the thesis analyses Aristophanes’ most prominent verbal, thematic, and theatrical modes of surprise from a typological perspective, and interprets them as comprising the key area in which the playwright claims and demonstrates his artistic superiority over rival genres and individual poets. In line with this purpose, two parallel aims of the thesis are to provide an original commentary on the passages under examination, and to promote the study of modern performances – a practice which has so far been either restricted to Classical Reception or only theoretically acknowledged (if at all) by mainstream philological scholarship.

Keywords: semiotics
Greek comedy
humour
performance
reception
Aristophanes
typology
poetics
Advisor: D'Angour, A
Synaptic plasticity models in brain development and neurodevelopmental disorders

Mathematical and computational models are powerful tools that can help us gain a deeper understanding about the world around us. In Neuroscience, however, there is still debate as to what the role of models is in research. In this thesis we build models of synaptic plasticity of varying degrees of complexity, and at different levels of abstraction in order to generate experimentally testable hypotheses and propose new ways of thinking about synaptic plasticity in development and in neurodevelopmental disorders. We applied our models to two datasets.
First, we studied a transient translaminar cortical circuit that connects layer 5b (L5b) interneurons with L4 excitatory spiny stellate neurons (SSN), or the L5b-L4 loop, that is present in the mouse barrel cortex during the first two postnatal weeks (Marques-Smith et al., 2016).. We used spiking neural networks and rate models with plastic connections to explore the mechanisms that drive these large connectivity changes, as well as the possible role these may play in the developing mouse barrel cortex.
Second, we analysed extracellular plasticity data recorded from Ts65Dn animals, a mouse model for Down Syndrome. We used three abstract models to formalise and test the hypothesis that synapses in Ts65Dn animals are more saturated, i.e. the baseline synaptic weights are closer to their maximum. First, we used a theory of synaptic plasticity that explicitly fit the baseline and the maximum synaptic weight, then we fit a descriptive phenomenological model, and finally, we adapted the Moran process, a model from evolutionary biology, to describe extracellular plasticity experiments.
The methodological differences between how experimental and theoretical work is carried out makes it challenging to integrate modelling into an experimental framework, and vice versa. However, through these five modelling examples, we argue that a successful model is not one that can capture all the features of the data, but rather one that can address the questions and hypotheses that cannot be studied with experiments alone.

Advisor: Vogels, T
Butt, S