VictorJuiz/thesis huggingface dataset:
Selection among replicators and protocell chemotaxis

This thesis describes a series of projects which have autocatalysis as the overarching theme.
Chapter 1 is a general introduction to the construction of chemical models of biological systems. There is a discussion of what mechanisms are used to achieve autocatalysis. The biomimetic work of chapters 3 and 4 use lipid replicators, so there is particular focus on the physical autocatalysis of lipid aggregates and their use in prebiotic models. The roles that lipids play in life are used as an illustration of the promise they offer to systems chemists. A brief history of biological homochirality is given.
Two designs for novel asymmetric autocatalytic reactions are described in chapter 2, both based on hydrogen bonding catalysis. Though neither system showed the desired amplification of chirality, this work led to the study of positive nonlinear effects within thiourea catalysis.
Projects which attempt to couple lipid replication with protocell behaviour are presented in chapter 3. In this chapter oil droplets are used as simple model protocells. Interestingly, feedback between the motion of droplets and a lipid forming reaction are observed, with the system showing striking chemotaxis. In the second part of this chapter other systems are used to explore the relationship between lipid formation and compartment division.
Chapter 4 describes observations relating to transient lipid replicators which can be fuelled to be maintained out of equilibrium. An initial finding shows that fuelling can result in dramatic oscillations, as well as stable concentrations. When lipids compete for resources, they typically show a succession through time, an interesting protocell model. Which replicating species dominates results from a multitude of combined effects which cannot be predicted simply using rates of formation of each lipid in isolation.
Finally, chapter 5 outlines the conclusions that can be drawn from these results and what future work remains.

Keywords: nonlinear effects
Origins of life
lipid world
nonlinear kinetics
asymmetric autocatalysis
protocells
organocatalysis
oscillating reactions
lipid replicators
small molecule replicators
synthetic chemotaxis
Advisor: Fletcher, SP
Illegal jaguar trade in Latin America: an evidence-based approach to support conservation actions

The Illegal Trade in Wildlife (IWT) is one of the most cumbersome threats currently facing biodiversity, with broad implications for the health and wellbeing of humans and nature. Over the past decade, reports of international illegal trade in jaguars (Panthera onca), with links to demand from Asian wildlife markets, have emerged throughout Latin America, raising the profile of jaguars as the emblem of Latin America’s fight against IWT. This DPhil is among the first to explore the characteristics, prevalence, and drivers of this threat to jaguars, with the goal of providing scientific evidence in support of ongoing and future projects and policies aimed at addressing it. Data collection efforts centred in Mesoamerica and Bolivia, two areas with varying degrees of evidence of international trade, and were based on interviews with enforcement agents and conservation practitioners, and questionnaire surveys with rural communities coexisting with jaguars. In both study areas, the illegal jaguar trade was found to be a prevalent, domestically-focused, and opportunistic activity, driven largely by the confluence of cultural traditions surrounding wildlife uses, forest-dependent livelihoods, and negative perceptions and interactions with jaguars, manifested through human-jaguar conflict. To a lesser degree, the trade was also influenced by a more diverse set of external actors and drivers than originally expected, including tourists of diverse backgrounds, regional immigrants, and traders of Asian-decent. Enabling factors ranged from critical limitations in the enforcement capacity of wildlife authorities, to a high social acceptability of jaguar killing in rural communities. Additionally, the DPhil highlighted biases in how those in charge of addressing the illegal trade in jaguars perceive and use evidence on the trade, with a tendency to disregard its reliability and conservation relevance. To address this issue, the DPhil provides guidelines towards a more objective decision-making on the illegal wildlife trade, and reinforces the need for evidence-based, multifaceted, counter-trafficking approaches that consider the complex interacting domestic and international, cultural and commercial drivers behind the illegal trade in jaguars.

Keywords: Jaguar
Decision-making
Illegal Wildlife Trade
Panthera onca
Big cats
Human-Wildlife Conflict
Carnivore conservation
Advisor: Milner-Gulland, E
Structural studies of the Type IX secretion system inner membrane complex

The Type IX Secretion System (T9SS) is a protein transport system found exclusively in the Bacteroidetes phylum of Gram-negative bacteria. The T9SS transports folded substrates across the outer membrane, including virulence factors of human pathogens, polysaccharide utilisation enzymes of environmental bacteria, and cell-surface adhesin molecules involved in Bacteroidetes gliding motility
The inner membrane proteins GldL and GldM use the proton-motive force to energise both the T9SS and the gliding motility apparatus. I present structures from five different species of the transmembrane core of the GldLM complex, solved using electron cryo-microscopy. The GldLM complex has two copies of GldM with one transmembrane helix each, surrounded by five copies of GldL with two transmembrane helices each. Most of the cytoplasmic domain of GldL was unresolved. I also present a low-resolution structure of the full length orthologous PorLM complex from Porphyromonas gingivalis.
Several polar residues are present in the transmembrane helices of GldL and GldM, suggesting that they may have a role in conducting protons across the inner membrane. I generated mutant strains where these polar residues were substituted with non-polar alternatives and found that some of these strains were deficient in T9SS and gliding motility. A universally conserved glutamate residue in GldL was essential to T9SS and gliding motility activity. In the structures of GldLM, one copy of this glutamate residue appears to form a salt bridge with a conserved arginine residue in one copy of GldM. I propose that a proton flow-dependent alternation of which copy of GldM is involved in salt bridge formation drives rotation of the GldM dimer, which spans the periplasm to connect the inner membrane and outer membrane components of the T9SS.
These results reveal the GldLM complex to be a third class of ion-driven rotary motor after the ATP synthase and the MotAB flagellar stator family.

Keywords: bacterial secretion
type IX secretion system
cryoEM
gliding motility
Advisor: Lea, S
Berks, B
Anti-microbial activity and inflammation in Hermansky-Pudlak Syndrome type 1

Inflammatory bowel disease (IBD) is caused by a breakdown in tolerance of the immune system to the gut microbiota in genetically predisposed individuals. The mechanisms underlying IBD are complex and multifactorial. Monogenic diseases with intestinal inflammation provide important puzzle pieces in identifying key mechanisms of barrier function. Hermansky-Pudlak Syndrome type 1 (HPS-1) features defective vesicle trafficking and can include complications such as Crohn’s-like intestinal inflammation and pulmonary fibrosis. In this thesis, I pinpoint aberrant immunometabolism in HPS-1 patient macrophages using transcriptomics and functional assays. Following bacterial infection, HPS-1 macrophages feature an augmented TNF/OSM signature, which underlies polygenic IBD. I validate the deregulated immunometabolism in HPS1 knockout HAP1 cells, which have defective cholesterol metabolism and enhanced low density lipoprotein uptake. Using lysosomal immunoprecipitation and proteomics, I identify increased mTOR levels on HPS1 knockout lysosomes, which translates into enhanced mTORC1 signaling. The amplified mTORC1 signaling in HPS1 deficiency is mediated by Rab32. The alterations in metabolism and mTORC1 activation cause impaired anti-bacterial immunity in HPS1 knockout cells and HPS-1 patient macrophages. Mass cytometry of HPS-1 peripheral blood reveals an expansion of inflammatory monocytes, while serum proteomics uncovers a TNF/IL-1α signature in HPS- 1. Suppression of mTORC1 signaling through rapamycin treatment rescues the bacterial clearance defect in HPS-1 patient macrophages, providing a novel therapeutic target for HPS- IBD. These findings have implications beyond HPS, since augmented mTOR signaling and derailed metabolism can trigger inflammation in several diseases, such as lysosomal storage disorders.

Keywords: Inflammation
Hermansky-Pudlak Syndrome
Anti-microbial activity
Monogenic disease
Inflammatory bowel disease
Advisor: Uhlig, HH
Combining digital histology with magnetic resonance imaging in amyotrophic lateral sclerosis

There is an increasing demand for non-invasive biomarkers that can reliably indicate the presence and extent of neurodegeneration in its early stages. Various magnetic resonance imaging (MRI) methods have shown great potential to indicate the event of upper motor neuron involvement in the progression of amyotrophic lateral sclerosis (ALS) at the population level, but almost none of these have been systematically validated against traditional histological markers at the individual level. Validation relies on a precise and preferably automatic method to align a large number of MRI and histology images of the same tissue, which poses unique challenges compared to more conventional MRI-to-MRI registration.
The thesis summarises the development and evaluation of a novel image registration framework (Tensor Image Registration Library) that is designed to achieve automated registration between sparsely sampled histology sections and whole-brain post-mortem MR volumes derived from an ALS study cohort. A multistage automated pipeline is developed, in which two types of histology sections are registered to an MRI volume via one or two photographic intermediates. The research chapters explain the rationale behind each stage, describe the algorithm, and report the experiments that were carried out to verify the accuracy and robustness of the implementation.
The proposed method uniquely integrates part-to-whole matching and 2D-to-3D registration, allowing conventional small histology samples to be registered without serial sectioning. Furthermore, the orthogonal deformations of a slice are estimated to account for the imperfections of a free-hand cut, which are shown to be as large as several millimetres. The pipeline achieves sub-millimetre accuracy in each stage and equally accurate alignment between histology and MRI when the stages are combined. This registration approach alleviates the need for specialist cutting or stain automation hardware, and is therefore suitable for integration into a wide range of studies that utilise routine neuropathology practices.

Keywords: biomedical imaging
multimodal
histology
MRI
software
tensor image registration library
amyotrophic lateral sclerosis
post-mortem
neuroscience
image registration
magnetic resonance imaging
TIRL
Advisor: Miller, K
Jenkinson, M
Jezzard, P
Foreign influence operations in the cyber age

After Russia’s interference in the 2016 U.S. election, influence operations gained great prominence in the public consciousness. Yet, International Security Studies lags behind. Our theories of public opinion formation are primarily from a pre-cyber age, and we lack answers to fundamental questions about influence operations as a tool of statecraft. How can we conceptualize influence operations? Is pretending to be a member of another state to influence foreign citizens a viable strategy? Does plausible deniability afford states the benefits theorized by existing covert action literature? I interrogate these questions to provide a better understanding of the psychological mechanisms and potential effects of foreign influence operations, contributing to the academic study of secrecy and to illuminating the threat democratic societies now face.
I begin with a concept-building paper, which proposes and defends a definition of influence operations and explains their prevalence today. This prepares the ground for an emerging research field and motivates the investigation of the benefits of secrecy. In the second paper, leveraging cross-national experiments, I challenge the conventional top-down model of cue-taking in International Relations. I show that elite cues do not have a significantly stronger impact than public cues on citizens’ attitudes towards a cyber-attack. This suggests that influence operations that attempt to influence mass attitudes by falsifying peer cues may allow foreign actors to benefit from secrecy for operational success. The third paper builds from the observation that politicians increasingly outsource disinformation work to private firms, but the assumption that they benefit from plausible deniability is untested. Results from an original experiment show that when governments are not implicated in an operation that originates in their country, they can avoid blowback and yet are no less effective at stirring paranoia or appearing omnipotent. I add the novel insight that the country of origin matters much more to Americans than the specifics of attribution.

Keywords: influence operations
public opinion
social media
disinformation
Advisor: Dill, J
Learning to integrate, waiting to belong: language, time and uncertainty among newcomers in Germany

What happens when we require newcomers to learn a country’s dominant language before they can work, study and become citizens?
At first blush, this may seem beneficial for newcomers and local communities alike. In fact, language proficiency requirements across Europe are often treated as innocuous components of broader immigration policies. However, recent scholarship in linguistic anthropology and related fields has demonstrated that such policies can, in practice, turn into significant sociocultural and economic barriers for newcomers. Understanding the impact of language requirements in the German context is particularly pressing: language learning is so central to German immigration and citizenship policy that it has become a core branch of a nationwide ‘Integration Programme’. Since 2015, Germany has granted asylum to over 1.1 million displaced people. Five years on, over 800,000 remain in Germany, most of whom are still seeking employment. How these nationwide programmes impact the everyday lived experiences and socioeconomic (im)mobility of newcomers in Germany is, however, largely underresearched.
My doctoral research has responded to these gaps through 15 months of in-depth ethnographic fieldwork within Berlin’s state-funded language and integration programmes for adult newcomers. Drawing on research in social and linguistic anthropology, I demonstrate that although these programmes are designed to accelerate newcomers’ socioeconomic incorporation, in practice they significantly delay their access to work, higher education and a sense of inclusion. What is more, in part because of the slowing effect these programmes have on their sense of progress, newcomers to Germany encounter temporal disruptions, which lead to acute experiences of stalling, boredom and temporal uncertainty. These findings contribute to enhancing our as yet limited understanding of the ways in which language is enmeshed in the temporal dimensions of migration and displacement, how policy-making impinges on experiences of temporal disruption, and what we can learn about newcomers’ positions of (un)belonging from their experiences of time.

Keywords: language policy
time and temporality
waiting
uncertainty
boredom
migration
forced migration
anthropology
integration policy
language and belonging
Germany
linguistic ethnography
Advisor: Olszewska, Z
Zeitlyn, D
Towards understanding of unconventional kinetochores in kinetoplastids

The kinetochore is the macromolecular protein machinery that drives chromosome segregation by interacting with spindle microtubules. Kinetoplastids, an evolutionarily divergent group of eukaryotes, possess a unique set of kinetochore proteins (KKT1—20, 22—25 and KKIP1—12) that lack significant similarity to known kinetochore components in other eukaryotes.
To date, KKT4 is the only component of kinetoplastid kinetochores shown to have microtubule-binding activities. However, the KKT4 structure and mechanism of action have so far remained unknown. In this thesis, I have shown that KKT4 forms oligomers and I have characterised the structure of KKT4 using X-ray crystallography, NMR spectroscopy and crosslinking mass spectrometry. I have shown that the microtubule-binding domain of KKT4 consists of a coiled-coil region followed by a positively charged disordered tail. Moreover, I demonstrated that the coiled-coil region is sufficient to interact with microtubules and the positively charged unstructured tail enhances the KKT4 affinity for microtubules. Key residues for the microtubule-binding activity have been identified using mutagenesis. I have also shown that KKT4 has DNA-binding activities in vitro.
The structure of the KKT4 C-terminal BRCT domain, revealed that the domain is a phosphorylation-dependent protein-protein interaction domain. The KKT4 BRCT domain interacts with a phosphopeptide derived from KKT8 and also makes direct contacts with the N-terminal region of microtubule-binding domain, suggesting possible regulation mechanism.
In the second part of this thesis, the structure and function of KKT23 acetyltransferase is reported. Using X-ray crystallography and NMR spectroscopy, the C-terminal region of KKT23 is shown to have a histone acetyltransferase domain which specifically acetylates histone H2A and H2AZ in vitro. The critical residues for the KKT23 catalytic activity are identified. Moreover, the N-terminal fragment of KKT23 for which no structural homolog is known, adopts a helical structure. Finally, KKT23 is shown to form a complex with KKT3 and KKT22.

Keywords: BRCT
kinetochore
KKT4
kinetoplastids
microtubules
trypanosoma brucei
Advisor: Akiyoshi, B
Redfield, C
The representation of the Second World War in Polish cinema 1945-1970: directors, the state and the construction of memory

This thesis provides an in-depth analysis of war films made in Poland between 1945 and 1970. The Second World War was an important topic for both filmmakers, and the government, and thus this genre provides a fascinating insight into the complex relationship between directors and the Communist Party during this period of rebuilding and political change. The government recognised the potential cinema held in creating and disseminating a socialist agenda, and creating a new national narrative of the conflict, that united the country around an image of unified resistance, and strong anti-German sentiment. This thesis will hypothesise that due to a number of factors, including the decentralisation of the film industry, the PZPR never fully controlled cinema, and as such a number of diverse images of the Second World War emerged during this period.
This work studies a selection of films from a number of leading directors, discussing their distinctive styles, and how their image of the war fit with the prevailing narrative of the time in which it was made. It will look at the circumstances surrounding film production and how the movies were received by reviewers. It examines the impact that the structure of the film industry; the changing political climate; and the experiences of the filmmakers had on the portrayal of the Second World War in cinema. It will also use this specific genre to investigate, and draw conclusions about the nature of censorship in Poland between 1945 and 1970.

Keywords: film units
memory
war cinema
Poland
Second World War
Polish cinema
Advisor: Evans, R
Addressing slavery and trafficking in UK and US public procurement frameworks

In this thesis, I undertake a doctrinal and normative analysis of public procurement policies seeking to eradicate slavery, servitude, forced labour and human trafficking (slavery and trafficking) from the supply chains of the UK and US Governments. Situated at the interface of public procurement law and human rights law, slavery and trafficking procurement policies must reconcile a diverse set of normative principles and goals in meeting the needs of stakeholders, including contracting agencies, contractors, workers in supply chains, and more remotely, taxpayers. I argue that while international human rights law does not require states to adopt slavery and trafficking procurement policies, it is desirable that the UK and US Governments do so in order to reinforce broader efforts in legislation, policy and the private sector to protect workers in supply chains from slavery and trafficking. The disadvantages of slavery and trafficking policies can be minimised through careful policy design. I then propose a theoretical framework drawing from public procurement principles (competition and fairness to contractors), public administration principles (clarity and specificity in rulemaking), and human rights principles (particularly the concept of human rights due diligence) to critically evaluate three UK and US slavery and trafficking procurement policies: contractor exclusions, contract conditions and award criteria. My analysis highlights that each policy in both jurisdictions fails to satisfy and maximise one or more of the theoretical framework’s key principles. To address this, I offer insights on how to make them more pragmatic, responsive to human rights goals and capable of effective implementation by procurement officers and contractors as part of their day-to-day procurement activities.

Keywords: public procurement
modern slavery
human trafficking
Advisor: Davies, A
Multi-pulse laser wakefield acceleration

This thesis presents results towards the realisation of high-repetition rate laser wakefield acceleration (LWFA). I have framed the contributions around the development of multi- pulse laser wakefield acceleration (MP-LWFA), which is a scheme using a train of laser pulses rather than a single pulse to excite a plasma wakefield. High energy but low peak power lasers that can reach multi-kHz repetition rates are already commercially available, and could become viable as drivers in the MP-LWFA scheme in the near future.
First, I discuss the development of a waveguiding mechanism capable of overcoming the diffraction length of the tightly focused laser pulses without suffering laser damage after continuous operation. I describe the novel solution of plasma channel waveguides and focus on the measurement of their densities using optical methods. This is challenging due to the small size (∼ 100 μm) and often low densities (n e ∼ 10 17 cm −3 ) of the plasma structures, leading to a low phase contrast. I discuss several techniques for measuring such structures, and methods for analysing the obtained data. Finally, I show how these methods are applied using data acquired from a recent experiment that was performed to produce plasma channels waveguides.
Second, I discuss the issue of ion motion and wakefield decay. MP-LWFA requires that the wakefields after each pulse in the train interact coherently to excite a wakefield through resonance. However, the interaction between the wakefield and the plasma ions lead to several instabilities which moves energy into other modes, eventually breaking up the wakefield. I present new experimental results measuring the wakefield decay time to be on the order of 100 plasma periods in hydrogen, which is likely to be sufficient for the MP-LWFA scheme.

Keywords: wakefield lifetime
laser wakefield acceleration
Advisor: Hooker, S
Walczak, R
Corner, L