VictorJuiz/thesis huggingface dataset:
Advanced control systems for fast orbit feedback of synchrotron electron beams

Diamond Light Source is the UK’s national synchrotron facility that produces synchrotron radiation for research. At source points of synchrotron radiation, the electron beam stability relative to the beam size is critical for the optimal performance of synchrotrons. The current requirement at Diamond is that variations in the beam position should not exceed 10% of the beam size for frequencies up to 140Hz. This is guaranteed by the fast orbit feedback that actuates hundreds of corrector magnets at a sampling rate of 10kHz to reduce beam vibrations down to sub-micron levels. For the next-generation upgrade, Diamond-II, the beam stability requirements will be raised to 3% up to 1kHz. Consequently, the sampling rate will be increased to 100kHz and an additional array of fast correctors will be introduced, which precludes the use of the existing controller. This thesis develops two different control approaches to accommodate the additional array of fast correctors at Diamond-II: internal model control based on the generalised singular value decomposition (GSVD) and model predictive control (MPC). In contrast to existing controllers, the proposed approaches treat the control problem as a whole and consider both arrays simultaneously. To achieve the sampling rate of 100kHz, this thesis proposes to reduce the computational complexity of the controllers in several ways, such as by exploiting symmetries of the magnetic lattice. To validate the controllers for Diamond-II, a real-time control system is implemented on high-performance hardware and integrated in the existing synchrotron. As a first-of-its-kind application to electron beam stabilisation in synchrotrons, this thesis presents real-world results from both MPC and GSVD-based controllers, demonstrating that the proposed approaches meet theoretical expectations with respect to performance and robustness in practice. The results from this thesis, and in particular the novel GSVD-based method, were successfully adopted for the Diamond-II upgrade. This may enable the use of more advanced control systems in similar large-scale and high-speed applications in the future.

Keywords: cross-directional systems
higher-order generalized singular value decomposition
fast orbit feedback
spatio-temporal systems
internal model control
Advisor: Duncan, S
Goulart, P
Information, access, and conflict: transnational interest groups and the politics of global tax governance

What accounts for variation in technical demand for business supplied information in tax policy processes at the OECD? This study explores the relationship between politicised international corporate tax policy processes and the participation of transnationally active corporate taxpayer interest groups. Existing ‘transnationalist’ tax IPE literature has largely neglected the role of transnationally active taxpayer groups and often deploys explanations centred on logics of ideas and socialisation to explain the nature of transnational tax policymaking (businesses – firms and their advocacy groups). In focusing exclusively on expert networks, much of this literature neglects the role of political interests in the transnational tax policymaking space. This dissertation therefore explicitly focuses on the under-researched study of transnational taxpayer interests by using an approach centred on interest group politics in the international tax policymaking process. The study focuses on why and when interest group input is demanded by policymakers in the OECD (delegates and technocrats), and what the role of intergovernmental conflict in the collective political principal plays in shaping OECD policymaker demand for taxpayer stakeholder participation in transnational tax policymaking. Bringing in insights from the lobbying literature on resource-exchange dynamics, this study evaluates how increasingly tough cooperation problems between countries, ultimately shape technocratic ‘demand’ for informational input from business. Th study explores the varying demand for transnational taxpayer stakeholder input in the OECD's recent work on corporate taxation (2012-2021) in three distinct eras that map onto underlying conflicts of interest with the collective political principal: (I) Transparency (II) Digital Taxation (III) Global Minimum Taxation. The study uses a qualitative methodological approach drawing on interviews and extensive document analysis.

Keywords: global tax governance
Advisor: Snidal, D
Production networks and planetary boundaries: challenges and opportunities for integrated assessment models

Integrated Assessment Models (IAMs) are used to understand the complex interactions between the Earth system and socio-economic processes. These models help us understand possible futures associated with different levels of human impact on the climate system. As such, they wield significant influence on policy-making and society as a whole. At the heart of this thesis is a fundamental inquiry into advancing IAMs. This deep inquiry is rooted in the understanding that the economy is a complex system and in the acknowledgement of the intertwined nature of the climate and ecological crises; both are mostly overlooked in IAMs. This thesis provides insights and advances for IAMs with the goal of strengthening their ability to address the climate and ecological crises together.
First, this thesis finds that IAMs are not up to the task of addressing the climate and ecological crises together. Using the Planetary Boundaries (PBs) framework, it assesses the ecological feasibility of Paris-compliant mitigation pathways that were considered in the recent IPCC Sixth Assessment Report. Almost all scenarios transgress PBs. Even “low-demand” or “sustainability” pathways do not meet the ecological feasibility criteria set forth by the PBs framework. These findings highlight the need for a comprehensive and integrated approach.
Second, drawing from complexity economics and recent findings in the literature on supply chain networks, this thesis argues that IAMs overlook key micro-level mechanisms that are essential for understanding the evolution, stability and resilience of the economic system – and thus of society as a whole. It explores how we might have a more fine-grained macroeconomic model that takes into account supply chain interactions at the firm level. It finds that serious data limitations must be overcome before we can achieve this level of granularity in IAMs. Using methods from complexity science, it addresses the data limitations using two different approaches and makes two major contributions: (1) it provides the first comprehensive picture of the most fundamental statistics on production networks, thus providing a basis for generating synthetic data or calibrating macroeconomic models; and (2) it provides the first thorough evaluation of a maximum entropy reconstruction method applied to firm-level production networks. This thesis also contributes to an emerging agenda to develop standards for data collection, cleaning and matching for micro-level production network data around the world.

Keywords: network reconstruction
firm-level data
missing information
production networks
planetary boundaries
maximum entropy
integrated assessment models
climate change
input-output analysis
supply chain networks
Advisor: Hepburn, C
Farmer, D
Lafond, F
Computational methods for rapid structural modelling of antibody-antigen interactions to improve identification of antigen-specific antibodies from BCR-seq data

Antibodies are immune proteins that are the basis of humoral immunity in jawed vertebrates, permitting highly-specific, mutable and lasting recognition of diverse foreign molecules. In their membrane-bound form, they are referred to as B cell receptors (BCRs): the collection of antibodies or BCRs in an individual is a record of their antigenic history, and tells us how their B cells have recognised and interacted with pathogens over their lifespan. Since the advent of next-generation sequencing and its application to these repertoires, we can sample and sequence the receptors of 103 to 106 B cells from a given individual. However, there remains an unmet need for mapping the mounting number of these BCR sequences to their putative antigen specificity. In this thesis, we aim to demonstrate how computational structural methods can be applied to BCR repertoires to improve our ability to identify antigen-specific antibodies.
In the first chapter, we describe a novel method for identifying antigenspecific antibodies from repertoire data using paratope prediction which we call "paratyping", and then use paratyping to discover novel Pertussis toxoidbinding antibodies from the BCR repertoires of transgenic mice.
Transgenic mice are a common source of therapeutic antibodies. To improve our understanding of the structural landscape of the BCR repertoires of these workhorses of antibody discovery, in the second chapter we apply structural annotation and modelling approaches to naive repertoires from humans, mice and transgenic mice. We show that the starting structural repertoires of transgenic mice are intermediate between humans and mice, despite being encoded by human genes, as a result of deficient junctional diversification in the primary repertoire of transgenic mice.
In the third chapter, we describe the creation of a novel sequence database for Ebolavirus-binding antibodies called EBOV-AbDab. Using this data alongside other techniques, we analysed the longitudinal BCR repertoires of 40 individuals vaccinated with Ad26.ZEBOV/MVA-BN-Filo. We used paratyping to predict the epitopes of the majority of the most expanded clonotypes after the booster vaccine, providing evidence of a highly convergent response to Ebolavirus vaccination that correlated with anti-Ebolavirus glycoprotein IgG titre.
Finally, in the fourth chapter we examine the growing body of nativelypaired data to try to understand VH:VL pairing preferences. We re-examine the VH:VL interface in the context of germline gene usage and subsequently analyse at scale the genetic pairing preference of antibodies in the largest paired sequencing repository, the Observed Antibody Space, in combination with 3x as much novel data produced by an alternative single-cell sequencing technology.
In the final chapter, I outline further work which can extend or complete the work presented in the previous chapters, as well as general outlooks for the field.
Optimal transport methods for analyzing highly multiplexed spatial proteomic data

Cell microenvironments are complex niches of interacting cells that drive tissue function and disease response. In recent years, in situ multiplexed imaging has en- abled the multi-molecular profiling of single cells while preserving their spatial con- text. Although these new technologies capture cell phenotypes and spatial organization at unprecedented resolution, the technology has many trade-offs, and the analysis of the rich spatial information they provide remains a challenge. In this thesis, we develop novel computational methods tailored for multiplex imaging data leverag- ing principles from Optimal Transport (OT), a branch of statistics for comparing probability distributions.
In the first part, we address the challenge of integrating spatial profiles from different tissues, a task essential to enhancing the information obtained from multiplex experiments. We introduce a novel algorithm for optimizing tissue alignment derived from partial OT, and additionally propose an unbiased statistical estimator for OT distances that scales to massive tissues at a fraction of the cost. We benchmark our method against state-of-the-art algorithms, and demonstrate our method’s improved robustness to rips, tears, and other challenging spatial distortions induced by the multiplexing process.
In the second part, we consider the task of quantitatively characterizing cell microenvironments. We introduce a novel framework that captures both microenvironment cell composition and spatial organization using graph OT, and demonstrate its applications in identifying cell-cell interactions, spatial domains, and disease relevant microenvironments on simulated and real datasets. On pathologist annotated mul- tiplexed lung tissues, we demonstrate that our methods recover microenvironments directly linked to known cell interactions and functions. On multiplexed head neck tumors, we identify microenvironments that are highly predictive of patient outcome. We benchmark our method against two state-of-the-art competitors and various base- lines, and show that our method outperforms all comparisons on each dataset.
Lastly, we present a comprehensive case study that showcases the practical appli- cation of both our methods for spatial integration and microenvironment characterization on a novel dataset of multiplexed mouse colorectal cancer tissues. We align massive tissues with hundreds of thousands of cells, and identify distinct, condition- specific microenvironment subtypes that correspond to unique cell enrichment profiles and spatial domains. Together, our methods provide a powerful approach to mapping the complex landscape of the tumor microenvironment in colorectal cancer.

Keywords: optimal transport
spatial biology
Advisor: Byrne, H
Leedham, S
O'Neill, E
Where do peacekeepers go? Unpacking the determinants of UNSC-authorized peace operation deployments

Where do peacekeepers go? A common assumption in the quantitative study of peace operations is that that peacekeepers are most likely to be sent to difficult-to-resolve conflicts. However, a closer look at the literature reveals that our knowledge on this issue is far from conclusive. Although we know that deployment is not random, we have yet to confidently identify the factors that drive this selection process. The present thesis revisits the question of where peacekeepers go. The starting point of the theoretical and empirical inquiry is the very beginning of the United Nation Security Council’s (UNSC) decision-making process. The first paper develops and statistically tests a novel theory on the role that interests of peacekeeping troop contributing countries can play in formal UNSC agenda-setting. The second paper explores the relation between the quality of the UNSC debates following agenda-setting and the time it takes the Council to authorize a first UN or non-UN peace operation to manage a civil conflict. The third paper presents novel time-varying data on 49 different mandate components of all UN and non-UN peace operations deployed to Sub-Saharan Africa between 1990 and 2019. This approach yields important insights on the role that interests from actors other than the fifteen Council members play in relation to where peacekeepers might eventually get sent. Furthermore, the empirical evidence presented in this thesis indicates that only certain conflict characteristics and attributes of the country experiencing civil strife play a role for the non-random assignment of UNSC-authorized peace operations.

Keywords: peacekeeping
civil war
UN Security Council
Advisor: Ruggeri, A
Snidal, D
Essays on macroeconomic policy

This dissertation consists of four self-contained chapters which discuss topics related to challenges and the design for macroeconomic policy in the aftermath of the Global Financial Crisis 2007-2008. The first two chapters consider the implications of the global financial cycle (GFC) to monetary policy in two-country open market dynamic stochastic general equilibrium models where the dominant role of the reserve currency in trade and global financial transactions can account for the cross-border transmission of U.S. monetary policy shocks. Chapter 1 evaluates the gains from international monetary policy cooperation between the financial centre and periphery countries. The key finding is that although monetary policy cooperation may improve the global welfare, the asymmetric policy spill-overs through the global financial markets create winners and losers from cooperation at the individual country level. Chapter 2 discusses whether exchange rate regime matters in the presence of the GFC with a similar model estimated to match the empirical evidence from a panel vector autoregressive (VAR) model. We find that even with a GFC, a peg substantially increases macroeconomic volatility. Conversely, the introduction of an additional policy instrument to manage capital flows dampens economic fluctuations. A tax on domestic credit achieves nearly equivalent results. Chapter 3 examines the effectiveness of unconventional monetary policy (UMP). We develop a theoretical model that underpins the `irrelevance hypothesis,' which states that UMP may make the effective lower bound (ELB) on the short-term interest rate irrelevant. We then test and firmly reject this hypothesis for Japan and the United States using a structural VAR model with the ELB. However, we find that UMP has had strong delayed effects. Chapter 4 analyses the factors that hinder the implementation of structural reforms using a macroeconomic political economy model. In the model, the effects of product market deregulation create its own resistance, and the resistance generates endogenous political costs to impair deregulation. In addition, adverse initial conditions, better risk-sharing among workers, and a lower share of temporary workers weaken opposition and help deregulation.

Keywords: structural reforms
political economy
currency mismatch
expenditure Switching
currency invoicing
monetary policy cooperation
dilemma
unconventional monetary policy
exchange rates flexibility
effective lower bound
structural VAR
monetary policy
foreign exchange liabilities
trilemma
product market deregulation
global financial cycle
Advisor: Ferrero, A
Immuno-molecular profiling and modulation of donor livers during normothermic machine perfusion


Normothermic machine perfusion (NMP) is an increasingly adopted preservation strategy in liver transplantation that facilitates organ assessment, safely prolongs preservation and is associated with reduced ischaemia reperfusion injury (IRI) related complications. However, these IRI-related benefits are less apparent in higher risk organs, which maintain a propensity to develop severe preservation injury despite NMP. The underlying mechanisms and contributory factors associated with this persistent injury are unclear, but may be related to molecular processes occurring during NMP or other preservation factors such as the length of cold ischaemia prior to NMP. This thesis aims to characterise the immunological and molecular processes occurring during NMP and devise interventions targeting these processes to reduce preservation injury. Through an evaluation of samples from clinical trials of human liver perfusion, I have demonstrated that ex situ reperfusion injury/inflammation (ERI) is an immunologically and molecularly distinct entity observed consistently across livers preserved with NMP. I have shown that the presence and length of prior static cold storage (pSCS) can impact the molecular signature of donor livers affecting key pathways and processes involved in mitochondrial function and cellular energetics. I have found that circulating damage associated molecular patterns (DAMPs), constitute an important element in ERI and alongside immune cells and inflammatory cytokines within the perfusate, propagate injury and inflammation ex situ, likely impacting the immunogenicity of the graft. I developed a large animal model to investigate these observations and explore possible modulatory interventions. Finally, I demonstrated that by mitigating ERI, ex situ graft function could be improved and preservation injury reduced in a porcine NMP model. This is achieved by the removal of highly pro-inflammatory nuclear DAMPs (neutrophil extracellular traps (NETs)/nucleosomes, free histones and cell free DNA) from the circulating perfusate during NMP with a specialised column.

Keywords: reperfusion injury
transplantation
organ preservation
Advisor: Friend, P
Metabolic engineering of Clostridium saccharoperbutylacetonicum for improved solvent production

In order to avert irreversible damage to the global climate, the global community has committed to reaching net zero carbon emission in the coming years. To meet this ambitious target, substantial changes will be needed. To minimise the disruption to people’s lives, there is a need for renewable technologies which are compatible with existing infrastructure, such as biofuels and drop in chemical compounds. A compound which can fulfil both roles is n-butanol. Clostridium are natural butanol producers but have fallen out of use as they have been unable to compete with fossil fuel-based production methods.
The aim of this thesis was to improve the production of butanol in an asporogenic strain of Clostridium saccharoperbutylacetonicum N1-4. A systems scale approach was taken to improve butanol production. Combined analysis of Clostridium metabolism using flux balance analysis and 13C-metabolic flux analysis was used to guide metabolic engineering strategies, with the aim of increasing butanol production in asporogenic C. saccharoperbutylacetonicum N1-4 spo0AI261T.
Flux balance analysis was used to gain an understanding of Clostridium metabolism and to explore manipulations that could lead to increased butanol production in wild type C. saccharoperbutylacetonicum N1-4. Key features of in silico engineered strains were compared to experimental data and identified an increase in NADH generation and key butanol synthesising genes as targets for increasing butanol production. A second round of flux balance analysis identified further manipulations relevant to C. saccharoperbutylacetonicum N1-4 spo0AI261T, mainly that the rate of glucose uptake appeared to be limiting butanol production. Simulations of strains with increased glucose uptake and butanol production suggested that ATP consuming enzymes would have to be engineered into the asporogenic strain to balance ATP.
Additional investigation was performed using 13C-metabolic flux analysis, which was able to resolve intracellular fluxes of asporogenic C. saccharoperbutylacetonicum N1-4. It also identified a feature of C. saccharoperbutylacetonicum N1-4 spo0AI261T metabolism that was unexpected, that ATP was in excess to biomass synthesis requirements, resulting in a futile cycle. The results from this flux analysis confirmed the rationale of the flux balance analysis guided strategies.
In the final chapter, the developed strategies were incorporated into the asporogenic strain of C. saccharoperbutylacetonicum N1-4. These mutant strains were analysed in fermentations. While none of the strains produced more butanol than the parent strain, this work incorporated several novel approaches to increase butanol production in Clostridium and will serve as a starting point for future metabolic engineering work.

Keywords: biofuel
butanol
Clostridium saccharoperbutylacetonicum
metabolic engineering
flux balance analysis
Clostridium
Advisor: Sweetlove, L
Howarth, M
Jenkinson, L
Nicolle, M
Manolopoulos, D