VictorJuiz/thesis huggingface dataset:
In vivo dynamic AFM mapping of viscoelastic properties of the primary plant cell wall

Plant development is a complex multiscale process out of thermodynamic equilibrium. While sophisticated mathematical models of this process exist, there are only a few studies which provide experimental evidence. At the cellular level, unidirectional plant growth can be described by the viscoelastic Maxwell (MW) model. At the subcellular level more complicated thermodynamic models exist for which experimental proof is missing, due to the lack of suitable experimental methods. Modern approaches in multifrequency AFM enable high resolution viscoelastic mapping for cells and polymers. However, these methods are based on the viscoelastic Kelvin-Voigt model and, therefore, the viscoelastic properties cannot be associated with plant growth. I provide a link between the generalised MW model and the AFM cantilever observables. Then I show that the primary plant cell wall (CW) behaves, at the subcellular level, like a standard linear solid (SLS). I further use the description of the CW as a SLS and the spatial information of the dynamic modulus to determine the characteristic quantities k∞, kM, η, and τ of the SLS with spatial resolution. The application of two eigenmodes suggests that it is possible to extend the approach from the SLS description to reconstruct the relaxation modulus of polymer networks. This is demonstrated by the stiffnessk2 and relaxation time 𝜏τ2 which are increased and decreased, respectively, compared to the first eigenmode. Finally, using the example of whole living seedlings of the plant Arabidopsis thaliana, I use this theoretical framework to demonstrate, that the viscoelastic properties at a subcellular level can be linked to thermodynamic models of plant growth. I show that these can be derived using the Onsager principle I develop a non-equilibrium approach to describe the time evolution of thermodynamic systems. Moreover, pharmacological and genetic manipulation of young seedlings indicates that these viscoelastic measurements can be used as an analytical tool to characterise CW deficiencies.

Advisor: Moore, I
Contera, S
Phenotyping cellular motion

In the development of multicellular organisms, tissue development and homeostasis require coordinated cellular motion. For example, in conditions such as wound healing, immune and epithelial cells need to proliferate and migrate. Deregulation of key signalling pathways in pathological conditions causes alterations in cellular motion properties that are critical for disease development and progression, in cancer it leads to invasion and metastasis. Consequently there is strong interest in identifying factors, including drugs that affect the motion and interactions of cells in disease using experimental models suitable for high-content screening. There are two main modes of cell migration; individual and collective migration. Currently analysis tools for robust, sensitive and comprehensive motion characterisation in varying experimental conditions for large extended timelapse acquisitions that jointly considers both modes are limited.
We have developed a systematic motion analysis framework, Motion Sensing Superpixels (MOSES) to quantitatively capture cellular motion in timelapse microscopy videos suitable for high-content screening. MOSES builds upon established computer vision approaches to deliver a minimal parameter, robust algorithm that can i) extract reliable phenomena-relevant motion metrics, ii) discover spatiotemporal salient motion patterns and iii) facilitate unbiased analysis with little prior knowledge through unique motion ‘signatures’. The framework was validated by application to numerous datasets including YouTube videos, zebrafish immunosurveillance and Drosophila embryo development. We demonstrate two extended applications; the analysis of interactions between two epithelial populations in 2D culture using cell lines of the squamous and columnar epithelia from human normal esophagus, Barrett’s esophagus and esophageal adenocarcinoma and the automatic monitoring of 3D organoid culture growth captured through label-free phase contrast microscopy. MOSES found unique boundary formation between squamous and columnar cells and could measure subtle changes in boundary formation due to external stimuli. MOSES automatically segments the motion and shape of multiple organoids even if present in the same field of view. Automated analysis of intestinal organoid branching following treatment agrees with independent RNA-seq results.

Keywords: collective motion
superpixels
temporal dynamic graphs
Advisor: Rittscher, J
Lu, X
Cybersecurity and non-state actors: a historical analogy with mercantile companies, privateers, and pirates

The thesis investigates how the historical analogy to mercantile companies, privateers, and pirates between the 16th and 19th century can elucidate the relationship between non-state actors and states in cyber(in-)security, and how such an application changes our understanding of cyber(in-)security. It contributes to a better integration of non-state actors into the study of cyber(in-)security and international security by clarifying the political challenges raised by the interaction between these players and states.
Drawing on the literature of non-state armed actors, the thesis defines a spectrum of state proximity to develop an analytical framework categorizing actors as state, semi-state, and non-state. The historical investigation utilizes primary and secondary sources to explore three periods in British naval history: the late 16th, late 17th, and mid-19th centuries. A comparison of the two security domains – the sea and cyberspace – identifies the pre-18th century periods as the most useful analogues for cyber(in-)security.
The thesis evaluates the analogy by conducting empirical case studies. First, the case of the attacks against Estonia (2007) and three criminal court cases against Russian hackers (2014/2017) examine the analogy to pirates and privateers. Second, the analogy to mercantile companies focuses on the attacks against Google (2009), the attacks against Sony Pictures Entertainment (2014), and the collaboration between large technology companies and Five-Eyes signals intelligence agencies.
The thesis makes three main claims: first, the analogy to piracy and privateering provides a new understanding of how state proximity is used politically by attackers and defenders, and offers lessons for understanding attribution in cyberspace. Second, the longevity of historical privateering sheds light on the long-term risks and rewards of state collaboration with cyber criminals, and offers insight into the political constitution of cyber(in-)security. Third, the mercantile company lens improves our understanding of how cooperative and conflictive relations between large technology companies and states influence cyber(in-)security.

Keywords: International Relations
Cyber Operations
Semi-State Actors
Non-State Actors
Cybersecurity
Cyber(in-)security
Advisor: Kello, L
Layers of modality

Much of the literature on modality focuses, at least implicitly, on the occurrence of single modal auxiliaries. However, cross-linguistically, modal auxiliaries can co-occur with one another, but under interesting restrictions. This thesis examines layered modal constructions and the semantic restrictions under which they combine. For instance, in languages such as Croatian, where double modal constructions are part of the standard, data shows that while some combinations are acceptable, others are not. Therefore, the aim of this thesis is to identify these semantic restrictions and to explain the rationale that motivates them.
To answer these questions, a systematic study of four possible combinations (epis- temics embedding epistemics, epistemics embedding non-epistemics, non-epistemics embedding non-epistemics, and non-epistemics embedding epistemics) was carried out. The data shows that the first three groups are, in general, acceptable to native speakers, while the last one is not. Further to that, the data shows that within the non-epistemic + non-epistemic group there seem to be further restrictions. The result was a hierarchical analysis that is based on modal force and flavour. With respect to force, it is shown in Chapter 4 that necessity embeds possibility, crucially, only when two of the same flavour combine. In terms of flavour, the data shows that epistemics can embed non-epistemics, while in the non-epistemic group priority embeds the circumstantial group in which pure possibility embeds ability and disposition, respectively. This analysis carries some important implications for the traditional categorisation of modal flavours which is discussed in Chapter 4. Finally, in Chapter 5 I also discuss the possible rationale behind the hierarchy and the compositional nature of DMCs. It is concluded that the hierarchy should not be taken as a merely descriptive generalisation, but rather as an analysis that is predictable on the basis of the conceptual and logical reality of human language.

Keywords: modal verbs
Croatian
Advisor: Asudeh, A
Husband, M
Segregation-assisted creep in nickel-based superalloys: experiments, theory and modelling

Mid-temperature creep deformation in the range of 600 to 850°C is assuming greater importance in Ni-based superalloys. This is because the design operating temperature of the combustion cycle is increasing as the new generations turbofan engines become more efficient. The temperature at the rim of turbine disks and the root of turbine blades can be in this critical range of temperatures for significant portions of the mission cycle, leading to a complex time-dependent mode of plasticity called "microtwinning"'. Unfortunately this kind of coupled displacive-diffusive deformation mechanism is not yet well understood, and even the range of temperatures and stresses where microtwinning occurs is not clearly defined.
This work explores the fundamentals of this phenomenon, from the kinetics of microtwinning to its influence on the mechanical behaviour of the material. To achieve this objective, coupled computational-experimental studies have been carried out. First, the contribution of microtwinning mechanism to the creep deformation of a single crystal superalloy is studied. The accumulated creep strain computed from quantitative stereology of the tested samples supports the role of this mechanism in conferring plastic deformation. Second, the chemical composition of the microtwins is analysed by means of atomic-resolution characterisation techniques (APT and TEM). Segregation of γ'-stabilisers to the growing faults is found to be crucial for the understanding of the creep mechanisms in this range of temperatures. Third, a model for diffusion-controlled growth of microtwins is proposed and used to recover the experimental creep strain rates. This then provides the basis for a thermodynamically consistent constitutive model developed on the basis of crystal plasticity theory. The constitutive model is subsequently implemented into a finite element code to study the activation of the different plastic mechanisms within single crystal and polycrystalline aggregates depending on the crystal orientation. With the support of this model, a relation between the rotations of the crystal and the creep life of the different crystal orientations is established. The numerical and experimental results ultimately reveal the critical role of the microtwinning on the asymmetric behaviour of the alloy and thus, its influence on the mechanical performance.

Keywords: creep
Advisor: Jerusalem, A
Reed, R
Vaccination strategies for cross-protective immunity against African Horse Sickness Virus (AHSV)

African Horse Sickness (AHS) is a highly lethal arboviral disease of equines. The lack of treatment makes vaccination essential. However, there are nine AHSV serotypes and AHSV immunity is serotype-specific; therefore AHSV vaccines must protect against all serotypes circulating in the field. A commercial polyvalent live-attenuated vaccine has been used for decades. However, bio-safety risks associated with its use, derived from gene segment re-assortment between vaccine and field strains, prompted the development of safer alternatives. These include the use of recombinant Modified Vaccinia Ankara virus (MVA). Previous studies showed that recombinant MVA vaccines expressing the AHSV outer-capsid VP2 protein successfully induced homologous protection and that a polyvalent MVA-VP2 vaccine could be developed (Manning et al., 2017).
MVA vaccines expressing full length VP2 or fragments thereof, including a truncated-VP2 lacking the central VP2 immunodominant region, indicated that the structural integrity of VP2 was critical for preservation of neutralising epitopes. Further studies aimed at enhancing MVA-VP2 immunogenicity showed that monovalent MVA-VP2, expressing full-length VP2 from 'immediate-early' vaccinia promoters, could be used in a multivalent vaccination regime inducing homologous protection.
To improve the design of polyvalent MVA-VP2 vaccines, a novel strategy based on using bivalent MVA-VP2, expressing two VP2 proteins from different serotypes, was proven successful. Homologous protection conferred by a bivalent MVA-VP2 for AHSV-4 and -9 was comparable to its monovalent counterpart.
Previous studies showed MVA-VP2 immunogenicity depends on levels of VP2 protein presented to the immune system at the time of vaccination, since purified MVA-VP2 failed to induce virus neutralising antibodies (VNAb). Further studies described in this thesis, showed the addition of carbopol adjuvant improved immunogenicity of purified MVA-VP2 vaccines.
MVA recombinants were produced expressing conserved AHSV capsid proteins, including VP5, VP7 and VP3, and immunogenicity of MVA-VP3 was tested which did not confer any protection against challenge. Various single and dual-expression MVA viruses were generated which will enable generating virus-like-particle AHSV vaccines by MVA expression, which has not been reported previously.

Advisor: Gilbert, S
Elucidating the molecular mechanisms underlying the endothelial-to-hematopoietic transition

Definitive hematopoietic stem and progenitor cells (HSPCs) are generated de novo from a subset of endothelium, the hemogenic endothelium (HE), via a process called the endothelial-to-hematopoietic transition (EHT). To facilitate the study of HE throughout this process, our lab generated a Runx1 enhancer-reporter mouse model (23GFP) to dissect the cellular and molecular events that underlie EHT. Previous work in the lab highlighted that HE undergoes dynamic fate changes already early in development characterized by two distinct states, a competent state (cHE) and a specifying stage (sHE). In the context of EHT, this study rewrote the timeline of hematopoietic commitment during EHT and showed this is initiated in sHE before the proHSC and type I and type II preHSC stages. My aim was to identify and characterize the gene regulatory interactions (GRIs) underlying these cell fate transitions. We reasoned that integration of expression (RNA-seq) and chromatin profiles (ATAC-seq) would facilitate identification of these GRIs. After validating and characterizing the data sets, we focused on TFs where the timing and appearance of the motif coincided with expression of the TF and identified these as putative regulators of accessibility and subsequent changes in gene expression. Focusing on two key cell fate transitions: (1) cHE to sHE and (2) sHE to proHSC, we generated GRI maps. Analysis of these regulatory interactions identified putative causative regulators, including Bcl11a, Mef2c, Ikzf1, and Ikzf2. Looking more closely at Ikzf1, we identified a -28 element required for proper Ikzf1 expression. Interestingly, -28 activity was Runx1-dependent. Further investigation identified Notch signaling as a downstream target of the novel the Runx1-Ikzf1 regulatory axis. Finally, interrogation of this regulatory axis using genetic perturbation revealed a complex interaction whereby Runx1 and Ikzf1 work both individually and synergistically to regulate Notch during in vitro EHT.

Advisor: De Bruijn, M
The why of geographical indications

This thesis explores the historical evolution of the nature of the link between a product and its place of origin in the European sui generis systems of GI protection, with a specific focus on the EU Regulation 1151/2012 on Geographical Indications for the protection of agricultural products and foodstuffs. It concludes that this link has substantively changed, since the 1930s, when some early forms of sui generis GI systems were introduced in southern Europe, especially in France and Italy. While these regimes were based exclusively on the concept of terroir, a cipher for the physical link between a product and a place, an empirical analysis carried out in the present work reveals that, today, the history of the product and of its method of production is, statistically, the predominant linking factor. Furthermore, the research shows that the historical link is almost always mentioned in the specifications of EU GI products, when protected both by Protected Designations of Origin (PDO) or Protected Geographical Indications (PGI), which are the two quality schemes provided by EU Law. In particular, the terroir element, which characterises PDOs, also appears frequently in PGI specifications, where it should be superfluous, thus suggesting that the differences between these two quality schemes are unclear. Finally, the emergence of the historical element confirms that GIs can contribute to the protection of products that are linked to a geographical area not by physical and environmental factors, but by the socio-cultural traditions of a specific place. Although history can constitute a valid product/link, however, it must be used with caution, as it can be mystified and reconstructed in an arbitrary and unfounded way. This is dangerous, because it can turn GIs into a mere marketing tool, thus damaging the origin function that distinguishes them from the broad family of quality labels.

Keywords: Intellectual Property Law
Common Agricultural Policy
Traditional Specialities Guaranteed
Rural Development
Protected Geographical Indications
Traditional Knowledge
EU Geographical Indications
Geographical Indications
Appellations of Origin
Protected Designation of Origin
Advisor: Gangjee, D
Predicting heart failure deterioration

Chronic heart failure (HF) is a condition that affects more than 900,000 people in the UK. Mortality rates associated with the condition are high, with nearly 20% of patients dying within one year of diagnosis. Continuous monitoring and risk stratification can help identify patients at risk of deterioration and may consequently improve patients' likelihood of survival. Current repeated-measure risk stratification techniques for HF patients often rely on subjective perception of symptoms, such as breathlessness, and markers of fluid retention in the body (e.g. weight). Despite the common use of such markers, studies have shown that they offer limited effectiveness in predicting HF-related events.
This thesis set out to identify and evaluate new markers for repeated-measure risk stratification of HF patients. It started with an exploration of traditional HF measurements, including weight, blood pressure, heart rate and symptom scores, and aimed to improve the performance of these measurements using a data-driven approach. A multi-variate model was developed from data acquired during a randomised controlled trial of remotely-monitored HF patients. The rare occurrence of HF-related adverse events during the trial required the developement of a careful methodology. This methodology helped identify the markers with most predictive ability, which achieved moderate performance at identifying patients at risk of HF-related adverse events, clearly outperforming commonly-used thresholds.
Subsequently, this thesis explored the potential value of additional, accelerometer-derived physical activity (PA) and sleep markers. For this purpose, the ability of accelerometer-derived markers to differentiate between individuals with and without HF was evaluated. It was found that markers that summarise the frequency and duration of different PA intensities performed best at differentiating between the two groups and may therefore be most suitable for future use in repeated-measure applications.
As part of the analysis of accelerometer-derived HF markers, a gap in the methodology of automated accelerometer processing was identified, namely the need for self-reported sleep-onset and wake-up information. As a result, Chapter 5 of this thesis describes the development and evaluation of a data-driven solution for this problem.
In summary, this thesis explored both traditional and new, accelerometer-derived markers for the early detection of HF deterioration. It utilised sound methodology to overcome limitations faced by sparse and unbalanced datasets and filled a methodological gap in the processing of signals from wrist-worn accelerometers.

Keywords: Actigraphy
Risk prediction
Signal processing
Heart failure
Advisor: Tarassenko, L
Rahimi, K
Political sociology of unity and division

Growing economic inequality and cultural heterogeneity has brought increased attention to the issue of 'unity in diversity', that is, the state of being joined together or being in agreement in the presence of actual and perceived differences among people. Despite the growing interest in 'politics in divided societies', many political-sociological aspects of this issue remain largely unexplored. At the heart of this thesis lies an interest in explaining how social forces shape political preferences regarding the tension between unity and diversity in contemporary democracies. More specifically, this research seeks to understand how social (and identity-based) cleavages affect public responses to the idea of solidarity-based welfare provision and the reconciliation of increased ethnic diversity with national unity (including the functioning of the welfare state). Drawing on the institutionalist view that pre-existing policy creates mass politics (policy feedback effect), the study also investigates whether institutional structures condition the association between social forces and political attitudes. Although several chapters put particular emphasis on policy feedback effects (e.g., Chapters 2, 3, and 5), they are still within the general scope of this thesis, that is, the 'social embeddedness of political attitudes'. The thesis consists of two parts: the first assesses the explanatory power of socioeconomic status and social policy structures in predicting public attitudes toward income inequality, redistribution, and taxation policies (Chapters 2 to 4), and the second examines how differences in occupational status and national identity result in differences in reactions to welfare chauvinism and multiculturalism (Chapters 5 and 6). Taken together, the findings of this study underscore the importance of social cleavages, identity, and institutional structures in explaining why and under what conditions people are more likely to sacrifice part of their private interest or particularistic identity for the common good or the general welfare of all individuals in a community, in a situation of growing economic inequality and increased cultural plurality.

Keywords: identity
group polarization
institutions
social solidarity
social cleavages
Advisor: Fisher, S