VictorJuiz/thesis huggingface dataset:
Optimization for and by machine learning
Keywords: Conditional Random Field
Continuous relaxations
Machine Learning
Optimization
Linear Programming

Optimization and machine learning are both extremely active research topics. In this thesis, we explore problems at the intersection of the two fields. In particular, we will develop two main ideas.
First, optimization can be used to improve machine learning. We illustrate this idea by considering computer vision tasks that are modelled with dense conditional random fields. Existing solvers for these models are either slow or inaccurate. We show that, by introducing a specialized solver based on proximal minimization and fast filtering, these models can be solved both quickly and accurately. Similarly, we introduce a specialized linear programming solver for block bounded problems, a common class of problems encountered in machine learning. This solver is efficient, easy to tune and simple to integrate inside larger machine learning algorithms.
Second, machine learning can be used to improve optimization, in particular for NP-hard problems. For problems solved by using hand-tuned heuristics, machine learning can be used to discover and improve these heuristics. We show that, for the problem of super-optimization, a better heuristic to explore the space of programs can be learnt using reinforcement learning. For problems where no such heuristics exist, machine learning can be used to get an approximate solution of the original problem. We use this idea to tackle the problem of program synthesis by reformulating it as the problem of learning a program that performs the required task. We introduce a new differentiable formulation of the execution and show that the fastest programs can be recovered for simple tasks.
Satellite remote sensing of volcanic plumes
Keywords: volcanic ash
SO2
volcanic plumes
satellite remote sensing
IASI

Volcanic plumes are one of many hazards associated with eruptions. Monitoring helps to mitigate against their effects, understand their environmental and climatic impacts, and interpret volcanic activity. While ground-based measurements are valuable, field campaigns and ground-based instrument networks are expensive and not always viable. Satellite remote sensing is a cost-effective alternative and can be used to track the propagation of plumes as they travel away from the source. This thesis explores some of the ways in which the Infrared Atmospheric Sounding Interferometer (IASI) can be used for this purpose.
A method known as CO2 slicing, commonly used to obtain the altitude of meteorological clouds, was adapted for IASI to find the altitude of volcanic ash clouds. The technique was first tested on modelled data, before being successfully applied to scenes containing ash from the Eyjafjallajökull and Grímsvötn eruptions.
The second part of this thesis explores how IASI retrievals can be used to monitor volcanic emissions of sulphur dioxide (SO2). A linear retrieval was first applied globally to identify sources of SO2, including emissions from explosive eruptions, non-eruptive degassing and anthropogenic sources. Emissions were commonly identified in Ecuador and Kamchatka and these were explored further with an iterative retrieval which quantified the SO2 amount in each region. The trends observed with IASI were similar to those seen with the Ozone Monitoring Instrument (OMI), and at Tungurahua, good agreement was seen with ground-based flux measurements.
The final chapter builds on this research by systematically comparing the upwind and downwind mean column amounts obtained with a linear retrieval at 166 volcanoes. This highlights the strengths and weaknesses of the retrieval and reveals emission trends at some volcanoes; sometimes agreeing well with trends from OMI and in thermal emissions. This simple procedure demonstrates the utility of using IASI for observing changes in volcanic emissions.
Developing novel scoring functions for protein-ligand docking using machine learning
Keywords: virtual screening
docking
machine learning
drug discovery
scoring function

Structure-based drug discovery uses information about the structure of a protein to identify novel ligands that bind to the protein. The fundamental problem in structure-based drug discovery is predicting if, how, and how strongly a possible ligand binds to a protein. This is often accomplished using scoring functions to rapidly estimate the strength with which a ligand binds to a protein -- its binding affinity. This thesis explores the use of machine learning techniques to improve scoring functions for protein-ligand binding affinity. We first analysed the features used by several published machine learning scoring functions, before showing that augmenting these features with ligand-based features can improve scoring function performance. We then compare the performance of different machine learning algorithms. We next perform a series of experiments to investigate how the size and composition of the training set, and its similarity to the test set, influences the performance of Random Forest scoring functions. We find that regardless of training set composition, augmenting structure-based feature sets with additional ligand-based features leads to enhanced scoring function performance on a diverse test set. We further investigate the predictions of a Random Forest using only ligand-based features, and find that, when a ligand has different binding affinities for multiple binding partners, this ligand-only model is predictive of the mean binding affinity of a ligand for its binding partners. Finally, we address the use of docked poses for the ligand instead of experimentally-determined binding modes. We find that pose prediction errors are common. We show that using docked poses in place of crystallographic binding modes reduces scoring function performance, and that augmenting a structure-based scoring function with ligand-based features can help to counteract this effect. We then construct a new data set and show that generalising to new data and novel targets remains challenging for machine learning scoring functions. In this thesis we examine whether the use of a more detailed representation of the physicochemical properties of a ligand can improve machine learning scoring functions for protein-ligand binding affinity
Understanding the role of islet development in type 2 diabetes susceptibility
Keywords: beta-cell
pancreas
transcriptome
iPSC
chromatin
diabetes
T2D
genetics
development
RNA-seq
type 2 diabetes
methylation
islet
genomics
ATAC-seq

Most variants associated with type 2 diabetes (T2D) predisposition in genome-wide association studies (GWAS) act through defects in insulin secretion. In principle, these could result from deficiencies in islet development and/or mature islet function: most functional studies have focused on the latter. To explore the contribution of disturbed islet development to T2D pathogenesis, I characterised the transcriptome (using RNA-seq), accessible chromatin (ATAC-seq), H3K27ac histone marks (ChIP-seq) and DNA methylation patterns (using the 850k Illumina array) of three human iPSC lines (from different donors) differentiated in vitro across 7 stages (n=24) of pancreatic beta cell development.
Principal component analysis, enriched pathways and transcription factors regulating the transcriptome and DNA regulatory marks analysed indicate that the hiPSC-derived model from which the data originated recapitulates key aspects of beta cell development, and achieves more adult beta cells (though still immature) than previously-published differentiation models. Analysis of differentially expressed genes and regulatory marks within each stage indicated that both the most adult stage (beta-like cells) and less differentiated stages were enriched in T2D-associated signals, pointing to the contribution of both developing and adult islets to T2D risk. Novel potential regulators of islet development were identified (e.g. REST or CUX2), including genes within loci associated with T2D by GWAS (e.g. PROX1, ONECUT1/HNF6) and TFs whose binding was disrupted by T2D-associated variants (e.g. CTCF, ZBTB33). The DNA regulatory information was used to lever the posterior probabilities of association of variants within each T2D-associated locus, refining fine-mapping at these developmentally active regions. Integration of DNA regulatory marks with transcriptomic information facilitated the identification of active enhancers in islet development and their possible target genes, including candidate gene effectors of T2D-associated variants.
One of these candidate genes, PROX1, was functionally tested in islet development in the laboratory, aiming to modulate its expression using CRISPR activation, interference, and knock-out. PROX1 was successfully upregulated in the undifferentiated hiPSC system using CRISPRa. Finally, it was possible to replicate the differentiation model in different cell lines (KOLFC2) than those that originated the omics data (SB). These new cell lines had the CRISPRa/i machinery integrated in the genome, providing more tools to study the effect of candidate genes in islet development and T2D.
Provenance of late Quaternary loess along the Middle and Lower Danube River, Europe
Keywords: Luminescence
U-Pb dating
Zircons
Loess
Geochronology
Hf isotopes
MARs
Provenance

Loess-palaeosol sequences along the Danube River are often the only Quaternary environmental and climatic archive spanning the whole last glacial-interglacial (and beyond) in Eastern and Central Europe. Despite long standing loess research their origins and formation processes are still debated. This thesis aims to fill this gap by investigating timing of deposition and provenance of loess deposits along the Danube River. The analysis pivots around geochemistry and geochronology.
Application of the latest luminescence dating protocols provides a basis for answering questions regarding the timing and rate of sediment accumulation, while detrital zircon U-Pb dating and Hf isotopes were utilised to better understand the source(s) of loess deposits along the Danube River. The timing of deposition and sediment origins provides insights into depositional history and sediment transport pathways.
The luminescence dating supports previous suggestions that loess deposits are not continuous and likely contain hiatuses. The hiatuses may not be spatially extensive, therefore high-resolution sampling approaches are critical to better understand these deposits. Further spatial analysis of mass accumulation rates shows deposition is not constant over time but varies greatly. Importantly comparison of multiple sites indicates that activity periods are not uniform spatially but rather site specific.
Provenance results show the Danube’s alluvium is the immediate geomorphological source of sediment for the loess profiles, indicating that sediment is predominantly transported over short distances. Rivers remain a crucial component of the source-to-sink loess model, though this research goes a step further showing that they are responsible for homogenising sediment, e.g. Danube sits on a mixing line between the Alp draining Sava and the Carpathian draining Tisza. Moreover, the results suggest that the Alps, Bohemian Massif and Carpathians are the main sediment proto-sources. However, for the first-time the importance of smaller not extensively glaciated mountain belts e.g. Dinaric and Balkan Mountains is shown which questions glacial action as a crucial sediment producing mechanism. Finally, the results suggest that sites along the Danube share sources and that sediment source remained unchanged over the Quaternary timescale.
Interactions between Turkish and Egyptian Islamic thinkers from 1908 to 1952: Modernity and the disruption of Islamic knowledge  
Keywords: Islamic intellectual history
Modern Islamic thought
Muslim modernism
Salafism
Political Islam
Egypt, Turkey, Late Ottoman

This thesis is an intellectual history of Late Ottoman Muslim thinkers and how they managed the epistemic disruption of nationalism, Islamic modernism, and the emerging discourse of Salafism. It studies the poet Mehmed Akif (1873-1936), sheikh ül-Islam Mustafa Sabri (1869-1954), and his deputy Zahid Kevseri (1879-1952), all of whom chose exile in Egypt as radical secular forces seized power in republican Turkey. The thesis argues they were the most influential figures in Late Ottoman religious thought, with a lasting impact on Turkish and Arab Islamism that has been obscured by disciplinary conventions that define writers and historical fields along ethnic, linguistic, and national lines. Through a deep reading of Arabic and Ottoman texts it traces their engagement with the ideas of Muhammad ʿAbduh, Muhammad Iqbal, Nasir al-Din al-Albani, Sayyid Qutb, and Said Nursi, outlining a broad history of Islamic thought in the modern period.
In Egypt Sabri engaged in extensive debate with the modernist tajdīd trend, which he saw as a calque on Enlightenment notions of religion. One of Mustafa Kemal’s most formidable critics, Sabri was alarmed to find Egypt’s intelligentsia advancing the secular, positivist agenda he had challenged in Istanbul, despite the absence of a Kemalist revolution. Kevseri (aka al-Kawthari) discerned a greater threat from the nascent Salafi movement, with its aggressive restatement of the theology advanced by Ibn Taymiyya and rejection of the juridical methodology of the Sunni legal schools. Kevseri resisted attempts to monopolise the term salafī because of the legitimation it conferred on those claiming to represent the belief and practice of early Muslims; following his death Kevseri’s fate was nevertheless to become al-Albani’s Other in the construction of salafiyya. However, Akif, a modernist who brought ʿAbduh’s thought into the Turkish sphere, made compromises with nationalist ideology that made of him an alternative intellectual mascot of the republic once political Islam gained currency.
Moral reasoning and action in war
Keywords: war
just war theory
ethics of killing
revisionism
communication
collectivism
uncertainty

The moral reasons we have to kill some people and not others in service to morally important outcomes – like winning a just war – are the central concern of this thesis. The three papers that comprise this thesis argue that reductive moral reasons – reasons derived from the ethics of individual self and other defense – apply in war and should figure in the individual and joint deliberation of soldiers when they decide whom they ought morally to kill. The focus on reductive moral reasons also aims to explain and defend “revisionist” just war theory and the philosophical methodology underpinning it known as “reductivism.” The explanations and defense respond to some familiar criticisms of revisionist just war theory. Each paper also defends a central idea of revisionist just war theory and reductive individualism. That is, that the morally best option in collectivized war is the morally best option in other contexts: distribution of unavoidable harms to those who bear the most responsibility for the circumstances in which those harms arise. The first paper defends revisionist just war theory and reductive individualism from the charge that it discounts the collective and political nature of war. First, it argues that any appeal to collective action tacitly appeals to individual morality in order to square with our intuitions about intentional defensive killing. Second, it argues that moral reasons derived from political self-determination either do not matter in war, or will not matter enough to override those reasons we can derive from the distribution of unavoidable harms to those who bear the most responsibility for the circumstances in which those harms arise. The second paper defends the relevance of revisionist just war theory to the way soldiers and armies fight. The paper does this by demonstrating that reductive individualism is the best way to account for the fact that soldiers kill in war to communicate reasons for action to their enemies. The final paper defends the relevance of revisionist just war theory to moral deliberation under the conditions of uncertainty. The paper develops an expanded understanding of the necessity constraint and adapts the comparative dimension of liability to a decision theoretic approach to acting under the conditions of uncertainty.
Graphene and Polymer Nanoparticle Electrocatalysis
Keywords: Single Entity Electrochemistry
Electrocatalysis
Nanoparticle
Graphene
Polymer

This thesis reports experimental work with two main aims: the first is the detection and characterisation of single graphene and polymer nanoparticles with an emphasis on their electrocatalysis; the second is to develop a more comprehensive understanding of nanoscale interfacial reactions kinetically and mechanistically. Understanding adsorption processes underpins applications in advanced catalysts and ultra-sensitive sensors. The adsorption of catechol on graphene nanoplatelets (GNPs) is first investigated and quantified electrochemically and spectroscopically. Two electrochemical techniques are applied, notably cyclic voltammetry of ensembles and nano-impacts of single particles to study catechol adsorbed on GNPs. Generic methodologies are developed for the study of surface adsorption on GNPs and a molecular phase transition is seen. This is further applied to first investigate the adsorption of phenyl hydroquinone, where a more complicated flat-edge-end adsorption manner is seen with two phase transitions, and second the role of adsorption in electrocatalysis, where a lower overpotential of dopamine oxidation at a single GNP as compared to glassy carbon is observed. This approach is then further protocolised and proposed as an accurate surface area characterisation technique for both graphene and graphene oxide materials with high surface areas and complex internal structures. In a second set of studies, the electrocatalytic behaviour of Nafion nanoparticles, a cation exchange polymer widely applied in fuel cells, is investigated. The catalytic oxygen reduction by ensembles and single Nafion particles doped with methyl viologen is investigated. The results reveal the relative kinetics of the ensembles and single particles and a generic novel approach to catalysis is proposed applying homogeneous electron mediators heterogeneously by immobilising the former in particles used to modify electrode interfaces. ‘Fake’ catalytic features of undoped Nafion particles are then fully explored, revealing the complexity in the voltammetry of electrodes modified by ensembles of nanoparticles. The ion transport and charge transfer within Nafion films and particles are then characterised and compared. The contrasting behaviour shows the transport in the particles is significantly faster than in films of similar thickness. This leads to the investigation and development of a novel type of reference electrode based on immobilisation of both components of redox couples within Nafion films. The proposed Nafion film reference electrodes demonstrate superior stability with respect to life-time and multiple cycling.
Revolutionizing the Party-state: The 1975 Chinese State Constitution
Keywords: China
Constitution
Cultural Revolution
Party-state

This dissertation argues that state constitutions reflect and temporarily freeze ongoing and haphazard interactions unfolding amongst actors and institutions. To investigate this claim, I examine China’s 1975 State Constitution. A remnant of the turbulent Great Proletarian Cultural Revolution (GPCR), the 1975 State Constitution has evaded all but a few scholars. Adopting elements from institutionalism, I show that the 1967 January Revolution as a “critical juncture” produced four separate results: (1) the “Revolutionary Committees” as a new form of revolutionary institution; (2) the organizational dominance of the military; (3) the importance of “revolution” as ideology and as a way to structure institutions; and (4) the Party as a new type of organization. Themselves emerging from seemingly random choices, these four sequences interacted and changed each other, leading to unintended consequences and eventually producing the 1975 State Constitution as a by-product.
My contribution is then three-fold: first, I advance a new reading of the GPCR that rejects interpretations based on the leadership having a master plan. Instead, I show that decision-makers were heavily constrained and more reactive than active. My argument then shows the dominance of structural over individual factors. Second, institutional actors are not rational. Actors are often unable to anticipate the consequences of their choices. Likewise, against the intentions of their creators, institutions often produce outcomes that reinforce or worsen problems instead of resolving them. Here, short-term fixes undermine long-term aims. Third, I provide a new understanding of how state constitutions work. Rejecting functionalist interpretations, I show how they are the result of unforeseen consequences resulting from decisions made in highly contingent situations. Given the recent constitutional amendments in China under Xi Jinping, this dissertation then enables us to rethink and reconsider current and ongoing trends.
Nature’s empire: the Darwinian idiom in late Victorian international thought
Keywords: International thought
Darwinism
Intellectual history
English School

This thesis explores the impact of Charles Darwin’s theory of evolution by natural selection on the international thought of late Victorian Britain. As the Darwinian revolution transformed Europe, so too did it prove generative of a new evolutionary idiom to theorise international relations. Yet the holistic nature of this Darwinian naturalism—implying as it did a basic unity of humanity under the laws of nature—did not sit easily with the prevailing bifurcating Victorian civilisational language so well-known in International Relations (IR). I thus track the contention and combination of these two modes of thought within Britain between 1851-c.1902 by excavating a Darwinian idiom of international relations which was prominent in this period, but so far under-studied.
In the first chapter I offer my novel methodological approach: a ‘concentric idiomatic history’, which shapes the thesis’ three-tiered structure. First is an exegesis of Darwin’s own writings, recast as a corpus of international theory, within which we find the foundational concepts of the Darwinian idiom. Thereafter, I track Darwin’s influence on a range of neglected political theorists of the period, exploring Darwinism’s transformation of three themes: savagery, war, and empire. Finally, I undertake an analysis of journalism and colonial administration to explore the percolation of such Darwinian notions into quotidian British imperial discourse and practice.
Genealogically, I argue that Darwinism’s radically flat worldview challenges IR’s interpretation of nineteenth-century international order as sharply bifurcated and governed by a ‘standard of civilisation’. Rather, in Darwinism, we find a ‘standard of nature’ which cut across European and extra- European demarcations far before the typically assumed endpoint of the dual order in 1945. In an ecological spirit, I thus close by calling for a new research emphasis on ‘nature’ in international thought, widening the aperture of historical inquiry beyond the well-trodden terrain of manufactured ‘civilisations’.