VictorJuiz/thesis huggingface dataset:
Systems-level analysis of the mitotic checkpoint
Keywords: Cell Cycle
Bistability
Spindle Assembly Checkpoint
Mitotic Checkpoint
Mathematical Model
Live-cell imaging

The mitotic checkpoint regulates a critical transition in the eukaryotic cell cycle. It delays exit from mitosis until all chromosomes have become bi-oriented. In spite of an impressive body of work uncovering mechanistic aspects of the mitotic checkpoint, a detailed understanding of how the mitotic checkpoint operates as a control system continues to evade us. Here, I present three systems-biological studies aimed at elucidating distinct aspects of the mitotic checkpoint control system.
Using a combination of dedicated experiments and mathematical modelling, we investigate the fragile response of the mitotic checkpoint to precocious separation of sister chromatids in Drosophila neuroblasts. We show that the lack of a robust response to precocious loss of sister chromatid cohesion results from systems-level crosstalk between error correction and the checkpoint effector module.
Applying dynamical systems theory in the analysis of a live-cell imaging dataset following the degradation of APC/C:Cdc20-susbtrates in RPE1 and HeLa cells that are arrested in prometaphase and treated with different doses of CDK1 inhibitor, we present a simple mathematical model of the mitotic checkpoint as parsimonious explanation for the observed response to CDK1 inhibition. The model gives rise to a bistable switch, which is discussed as a useful tool to conceptualise the transition of from prometaphase to metaphase and from metaphase to anaphase in terms of disengagement and inactivation of the mitotic checkpoint.
Employing a simple mathematical model of phosphatase regulation at mitotic exit as a tool in the analysis of a phosphoproteomics dataset, we examine how the decision to silence the checkpoint is dispatched to initiate diverse processes underpinning mitotic exit. We identify new substrates of the phosphatase PP2A:B55, and describe a mechanism whereby substrates are recognised by PP2A:B55 and their rate of dephosphorylation is encoded electrostatically.
Mechanisms and prevention of protein aggregation
Keywords: NMR
Aggregation
Amyloid

The deposition of amyloid in the central nervous system is associated with prevalent neurological disorders such as Alzheimer's and Parkinson's disease. This thesis studies the mechanisms and prevention of amyloid formation in vitro. We speciﬁcally focus on Parkinson's disease associated α-synuclein (α-syn). Using novel labeling methods we introduce NMR observable labels onto lysosomal protein glucocerebrosidase (GCase), a leading cause of Parkinson's disease. By introducing NMR active labels we are able to study GCase dynamics and screen potential drug therapeutics (chapter 3). Furthermore, we analyze the three way interaction between GCase, α-syn and lipids. We conclude that GCase is able to effectively chaperone α-syn under lysosomal conditions, both preventing amyloidogenesis and destabilizing mature amyloid ﬁbrils (chapter 4). Additionally, a model chaperone-aggregate system is investigated to gain insight into the mechanisms of small heat shock protein chaperoning, and how such mechanisms prevent aggregation (chapter 5). Finally, a high resolution crystal structure of RNA editing enzyme Cid1 is presented, whilst not directly linked to aggregation, many of the techniques used in this thesis were ﬁrst developed on Cid1 (chapter 7). Together, we utilize NMR, X-ray crystallography, electron microscopy and native mass spectrometry to elucidate aspects of protein aggregation mechanisms and prevention.
Teaching Philosophy at Key Stage 3: An intervention in pedagogical strategies in selective grammar schools
Keywords: MLT
Teaching
MLT2016
Teaching Philosophy

This dissertation discusses the importance of task design when planning lessons. This action research project gave me the opportunity to think about the importance of task design and think about what is the point in the tasks as teachers we plan.
I carried out evaluation of my own personal historic lesson plans to help understand the planning of tasks and then planned two schemes of work. These schemes of work were planned and developed with the use of literature, students’ feedback and my own personal reflection. Learning diaries were used in the second feedback to give students more ownership of their learning and inform me for future planning.
Findings indicated that knowledge is an important factor when planning lessons and developing task design. Knowledge should be at the forefront of planning. Knowledge has been discussed in detail (Firth, 2015b, Lambert, 2011 & DfE, 2013). The introduction of the new curriculum has allowed knowledge to be at the forefront of planning and given teachers the opportunity to think about task design centred around knowledge. Enquiry learning was also thought about with knowledge. Enquiry learning is a complex idea that needs to be carefully used in lessons to ensure knowledge is not lost.
Investigations of improved heat transfer instrumentation for cooled turbine stages
Keywords: Heat Transfer Instrumentation

This thesis describes the development of heated double-sided thin film gauge configurations for transient heat transfer measurements. By heating the substrate it is possible to measure the heat flux over a range of wall temperatures, which improves the resulting regression and leads to a more accurate determination of the adiabatic wall temperature and the heat transfer coefficient. The heated gauges can be used to measure the heat transfer of a film-cooled high-pressure turbine stage with engine-realistic combustor exit flows (hot-streaks and swirl) in order to study turbine aero-thermal performance in the presence of cooling flows. This thesis also presents the aerodynamic and heat transfer design as well as the mechanical assessment of the first fully cooled turbine stage for the Oxford Turbine Research Facility (OTRF). The high-pressure turbine stage is designed for lean-burn combustor interaction effects and has engine-state external cooling features.
Platinum thin film resistive gauges are the most advanced instrumentation for transient heat transfer measurement where high frequency response is required. Double-sided thin film gauges, consisting of two thin film temperature gauges mounted on either side of an insulating layer, have the advantage that the driving temperature difference is directly determined at the point of interest. A new gauge design is presented, which combines double-sided thin film gauges with the possibility to heat the substrate layer. Two arrangements of heated gauges have been developed, namely double-sided gauges with an underside thin film heater and self-heating double-sided gauges. These gauges yield an improved regression without the need for complex heating systems. The lateral conduction effects have been investigated using analytical models. The performance of different gauge types is quantified based on the quality of the regression. The heated gauge arrangements have been tested in the OTRF under engine-representative conditions on uncooled and cooled MT1 high-pressure nozzle guide vanes. Measurement strategies have been implemented to obtain the time-dependent temperature trace over a range of heating powers and calculate the convective heat transfer. This improved measurement technique allows for an accurate determination of non-dimensional parameters such as the Nusselt number and the film cooling effectiveness.
Zakat in Nablus (Palestine): Change and continuity in Islamic almsgiving
Keywords: ethics
calculation
lateral disciplining
generosity
social interactions
personhood
plasticity
social life of Islamic discourse
modern state
ethnography
abundance
surveillance
anthropology
rizq
state
poverty
Islamic system of value
thawab
Islam
public gaze
scarcity
value
sadaqa
political economy
security
ethical tradition
capitalism
self
tawakkul
paranoia
zakat
discursive tradition
repression
exchange
wealth
gift
inflection

The anthropology of ethics is a project of developing a common language in order to describe and to analyse ethical tensions as they manifest themselves across different traditions as well as changing social and historical contexts. Based on ethnographic fieldwork in the Palestinian city of Nablus in the West Bank, this thesis contributes to the anthropology of ethics with an analysis the virtuous spending of wealth – with a particular focus on zakat (Islamic almsgiving) – as it emerges through the Islamic discursive tradition. This stirs up wider issues, such as the trajectory of an ethical tradition in a politically repressive context. Historically, Nablus has been subject to different instances of foreign rule. Since 1967, the city has been under Israeli military occupation.
This thesis shows how social interactions constitute a field of ethical practice. References to the Islamic Scriptures surfacing in greetings, conversations, and transactions in Nablus can be read as invoking an Islamic system of value. Acts of generous giving are sometimes inserted into this system, which unfolds in the context of the political economy of Israeli occupation. In this wider landscape, zakat in Nablus emerges both as (1) a socially embodied virtue realized within and through social relations; and as (2) an institutionalized practice carried out by zakat institutions, which since the 1970s have mainly evolved in a legal framework defined by state of Jordan. Analysing zakat on these two levels, this thesis grants insights into how military occupation, modern state administration, and capitalism fragment and inflect the Islamic discursive tradition, e.g. by foregrounding certain aspects of the Scriptures over others. With a view to embodied practices of zakat and ethical interactions, Islamic discourse manifests a certain plasticity and continuity. Conceiving wealth and scarcity as inherently ethical problems rooted in social interactions, the Islamic tradition notably provides a conceptual language of wider relevance.
(De)contextualising Buddhist aesthetics
Keywords: vipassanā meditation
Buddhist practice
Buddhist emptiness
mindfulness
video art
performance
contemporary art
installation

(De)contextualising Buddhist Aesthetics is a practice-led artistic research project focusing on the interchanging transition between Buddhist and artistic practices. Essentially inspired by the concept of vipassanā meditation, I created a series of performances involving repetitive actions centring on the tasks of re-arranging readymade objects into multiple precarious configurations. Many exercises challenge the laws of gravity and other physical limitations of objects, as well as encouraging the learning experience through the process of trial and error. During the course of mindful observation of the performing body and objects, the mental state gradually gains moments of stillness and silence, which approach the meaning of emptiness (suññatā) in Buddhism. Repeated failures generate intermittent feelings of exhaustion and disappointment, which naturally become part of the progress, and can be personally used to develop insight into the notions of impermanence and the non-self derived from dhamma (Buddhist teachings). The video and photography documentations were edited and altered to generate a visual experience that echoes my thoughts and feelings developed during the proceedings; these moving images later inspired other series of hand-made artworks, including collages, drawings and paintings on paper and canvas, exhibited as part of the installations. Various techniques were applied so these objective components resonate a comparative experience of uncontrollability and controllability: dynamic and stillness, fast pace and slow rhythm, abstract and representation. Some two-dimensional pieces are transformed to three-dimensional and their displays keep changing from location to location, and from time to time, in conjunction with an unstable state of the mind. All artworks were created in various formats and interrelate and inform each other. They act together as evidence of the endless journey of artistic learning, which also mirrors the concept of self-learning in Buddhist meditation.
Genetic analysis of variation in complex traits
Keywords: Genomics
Variation
Complex trait
Genetics

Variation is a universal property of life, and much of contemporary genetics research is directed towards understanding the causes of variation in traits. Here I present the results of my investigations into the genetic and other causes of trait variation in humans and mice. I address these questions in the context of two distinct research projects, which use pre-existing data to investigate the causes of trait variation, through a range of analytic techniques.
I first extract trait data from historic breeding records from the incipient Collaborative Cross (a genetic reference population of recombinant inbred mice) and use them to map genetic factors affecting litter size and other reproductive traits. Mapping reveals significant quantitative trait loci associated with litter size and time between litters, as well as a number of suggestive loci. I characterise the genetic effects at these loci and investigate candidate genes. The most robust finding, a litter size locus on chromosome 5, explains around 3% of observed variation and 24% of the variation attributable to genetics.
Using data obtained from the Netherlands Twin Registry—a longitudinal database of Dutch twins—I investigate the prevalence of parent of origin effects on gene expression traits in peripheral blood in humans. I first phase individuals’ genotypes by parental origin and use these genotypes to calculate the heritability of over 44,000 gene expression traits partitioned into that attributable to matching and nonmatching parent of origin. I replicate prior genomewide heritability estimates for many traits, but I find little evidence of widespread parent-of-origin effects on human gene expression in blood. On further examination, the small sample size severely limits the power to detect such effects. Nonetheless, I identify approximately 200 genes enriched for immune system processes that show evidence of parent-of-origin-specific effects on heritability.
Investigation of cross-reactive antibodies against Plasmodium falciparum-infected erythrocytes
Keywords: Plasmodium falciparum
Antibodies
LAIR1

Cross-reactive antibodies have recently come into focus as promising tools for targeted vaccine design in the fields of HIV and influenza, but the identification of such antibodies that bind to Plasmodium falciparum-infected erythrocytes has proven difficult due to extensive clonal antigenic variation on the surface of these cells. In this study, I report the identification of cross-reactive human monoclonal antibodies that bind to P. falciparum-infected erythrocytes from most parasite strains tested. These antibodies gained broad reactivity through the insertion of a large piece of DNA between the V and DJ segments of the antibody heavy chain, which is encoded on chromosome 14. The core of the insert, which is the primary element required for binding to the infected erythrocytes, codes for the collagen-binding domain of LAIR1, an immunoglobulin superfamily inhibitory receptor that is encoded on chromosome 19. In each of the donors studied, the LAIR1-containing antibodies were derived from a single B cell clone and acquired mutations that increased binding to infected erythrocytes and reduced binding to collagen. The targets of these antibodies were identified as members of the RIFIN variant surface antigen family. The LAIR1-containing antibodies were able to opsonize and agglutinate P. falciparum-infected erythrocytes, suggesting that they may be useful in reducing parasite burden in vivo. Using newly developed assays, I show that the presence of LAIR1-containing antibodies is not limited to a particular place or population, but can be found quite commonly in individuals from different malaria-endemic areas. These findings demonstrate a novel pathway of antibody diversification by interchromosomal DNA transposition that results in the production of functional antibodies and suggest that RIFIN epitopes that are recognized by the LAIR1-containing antibodies may be potential candidates for the development of a blood-stage malaria vaccine.
Socioeconomic risk and the class-basis of reasoning during market transitions
Keywords: post-communist
marketization
Transition Economies
signal detection theory
identity economics
social identity theory
social class

This dissertation investigates the nature by which social class membership and identity figure in judgements of transition institutions for the citizens of post-communist Central and Eastern Europe. Using a unique dataset and a series of novel conceptual frameworks, it argues that social class is, in effect, an operationalisation of socioeconomic risk and vulnerability—a premise from which several important implications derive. Drawing on social identity theory, it presents and tests a model of self-conceptualisation, grounded in the belief that individuals variously identify with their social classes, depending on their perceptions of shared socioeconomic risk. From this, it follows that strong identifiers should derive more relevant information about the emerging market system from class-level economic experiences, and therefore accord these cues greater weight in judgements about transition institutions. Beyond testing this theory of interpersonal variation, it invokes signal detection theory from cognitive psychology to determine whether cross-group differences in economic vulnerability are responsible for observed class differentials in reliance on class-based economic cues. It then takes a wider view of class-based economic cognition by considering how the process of transition, itself, influenced the evaluative calculus of post-communist citizens. Building on cognitive mobilisation theory in political science, it is posited that on-going exposure to the prevailing economic system endows these citizens with the ability to link their class-level economic experiences to the effects of the market mechanism. The analysis largely supports the constituent hypotheses, as well as the larger notion that perceptions of shared socioeconomic risk led social class experiences to figure prominently in the minds of post-communist citizens.
Testing coherence in narrative film
Keywords: Coherence
Comprehensibility
Film As Film
Tension
Victor F. Perkins
Film Criticism
Film Studies
Intelligibility
Narrative Film
George Wilson
Close Reading

This thesis aims to explore how narrative films that are marked by crucial obscurities and explanatory gaps in their development manage to become coherent. More specifically, the thesis is interested in examining how these obscurities and explanatory gaps can be understood as meaningful aspects of the films' organisation.
Since the function of coherence in film has rarely been examined directly, the thesis first attempts to illuminate it by drawing on the work of two aestheticians who have examined it more systematically. Thus, the first part of the thesis discusses the work of Victor F. Perkins and George Wilson, while attempting to explore aspects of the work of these two aestheticians through the analysis of specific films. The writings of Perkins and Wilson provide a good starting point for the thesis because they raise crucial questions regarding the ways through which narrative films manage to deal with significant tensions in their organisation and intelligibility.
The main body of the thesis (the second part of the thesis) then examines four narrative films, each of which is marked by a significant aspect of apparent incoherence. In each case, the thesis attempts to show that this aspect of apparent incoherence – rather than merely obstructing the film’s intelligibility – essentially contributes to the creation of the film’s idiosyncratic internal logic. In order to understand how this becomes possible, the thesis pays close attention to the ways in which the various components of each examined film relate to each other, observing and analysing the aesthetic strategies which enable each examined film ultimately to come together.
Essays in education economics
Keywords: Education policy
Non-cognitive skills
Early education
Returns to education
Maternal labour supply
Peer effects

This thesis examines three different aspects of education policy to ascertain their effects on individual outcomes, both in the classroom and in the labour market. The goal is to provide new empirical evidence using robust identification strategies that can inform better policy.
The first chapter looks at the role of pre-primary education in Germany using the German Socio-Economic Panel data set (GSOEP) to determine if attending an early education programme for longer increases the probability of attending a higher-level secondary school at age fourteen. I employ family fixed effects estimation and quasi-experimental analysis to control for selection. The results of the family fixed effects estimation show a small and negative impact of attending early education for more years. In the quasi-experimental analysis, based upon a federal law change in 1996, I find no impact of more years of early education on later schooling outcomes.
In the second chapter of this thesis, I again use the GSOEP to examine the recent German reform to extend the length of the primary school day. I exploit the quasi-experimental roll-out of reform to assign treatment to women and look at whether increasing school hours increases the likelihood that mothers enter into employment or extend their hours if already working. I find that the policy has an effect at the extensive margin, drawing more women into the labour market, but that there is no significant impact of the policy at the intensive margin.
In the final chapter I turn my attention to how peers' non-cognitive traits impact an individual's learning outcomes. Using an educational panel from Flanders, Belgium, I use the linear-in- means model of peer effects as well as several non-linear models to see how peers’ personalities in a classroom affect Dutch and math scores. The results show that having more conscientious peers on average positively impacts Dutch and math scores, but that a greater dispersion of conscientiousness hurts Dutch outcomes. I also find that having more extroverted peers on average hurts math performance.