VictorJuiz/thesis huggingface dataset:
A CRISPR-Cas9 screen for hepatocyte receptors for malaria parasite invasion

More than 2 billion people are at risk of contracting malaria, and around half a million die every year. Malaria is transmitted by sporozoites from Anopheles female mosquitoes to human host during a blood meal. From the host dermal layer, sporozoites travel to the liver, traverse through multiple hepatocytes until stopping in one last cell. They then establish a productive cell invasion, followed by a parasitophorous vacuole formation. Inside this vacuole, sporozoites develop into thousands of merozoites which are later released by hepatocyte rupture. Then, merozoites travel to the blood vessel to invade erythrocytes where malarial clinical symptoms appear– as such, preventing the liver stage infection can protect infectees from clinical onset. However, the liver stage remains a poorly understood malaria stage today owing to its complex molecular cell invasion mechanism. Therefore, in order to understand how sporozoites establish a hepatocyte invasion and which host cell surface receptor-sporozoite surface ligand interaction is involved in this event, CRISPR-Cas9 screen technology was applied in this study. 480 genes were knocked out, and their impact on the sporozoite invasion was assessed. Initially, results showed ITGAV, RPN1, ATP2B1, TMEM30A, FCGR2B, ITGB5, SLC35A2, MGAT1, EMC1 and APOH genes as hits. Amongst these, ITGAV and ITGB5 (αVβ5 integrin) were investigated as αV-integrin is a known binding partner of TRAP. However, further experiments revealed that ITGAV and ITGB5 hits were false positives induced by a lack of cell adhesion due to integrin disruptions rather than a direct binding activity with the sporozoites. Nevertheless, the CRISPR-Cas9 screen method used for this study remains a useful tool in studying hepatocyte-sporozoite protein interactions due to its success in identifying hepatocyte surface proteins, SR-B1 and ApoH, which are known to be important for the malaria liver stage. Therefore, this study presents an effective method to study parasite-host protein relationships by incorporating a sporozoite invasion assay with a CRISPR-Cas9 screen.

Keywords: CRISPR
sporozoite
liver stage
CRISPR-Cas9
malaria
Advisor: Douglas, A
Spencer, A
Effects of altering CpG dinucleotide composition in small DNA viruses

CpG dinucleotides are underrepresented in mammalian genomes and in many viruses infecting them. Previous studies have shown that increasing CpG frequencies in various RNA viruses and retroviruses reduces replicative fitness but the effects of this compositional modification are unknown in DNA viruses. To investigate this, the effects of increasing CpG frequencies were determined in the parvovirus minute virus of mice (MVM) at various stages of the viral life cycle and a system was set up for the murine polyoma virus (MPyV).
Part of the VP gene (24.4 % of the viral genome) of MVM was replaced by synonymously coded inserts with a CpG-high sequence and several other compositional mutations. Infection time courses and TCID50s were performed to test replicative fitness. Genome copy numbers and viral RNA levels were measured via RT-qPCR. Immunofluorescence, western blots and in vitro translation were used to visualise and measure protein production and distribution. Knockout cell lines were used to find antiviral mechanisms involved.
Compared to the wild type and scrambled virus, CpG-high viruses showed impaired growth curves in vitro. Immunofluorescence assays showed that the CpG-high viruses could establish infection and protein production in fewer cells. RT-qPCR revealed that viral mRNA levels were reduced in the CpG-high mutant, a phenotype that partially reverted in ZC3HAV1 (ZAP) knockout cells.
Increasing CpGs in MVM led to reduced mRNA levels, which impacted all aspects of the viral life cycle, leading to fewer productively infected cells and reduced viral progeny numbers though there might be further restriction later in the replication cycle. This is thought to be due at least in part to selective recognition of CpGs in RNA by ZAP.

Keywords: CpG dinucleotide
TpA dinucleotide
zinc antiviral protein
codon optimisation
minute virus of mice
parvovirus
Advisor: Simmonds, P
Klenerman, P
Mechanics and control of perching flight

Perching is an example of high risk, high reward behaviour executed within tight physical constraints. Despite the high risks posed by collision and stall, perching is performed routinely by most birds. However, surprisingly little is understood about the energetics and control of aerodynamic braking, nor the detail of wing and tail kinematics during perching.
In this thesis, detailed wing and tail kinematics were quantified for over 1000 indoor perching flights by Harris hawks using high-speed motion capture. Similar measurements were also taken from 15 outdoor flights by a Steppe eagle, and trajectories were tracked from wild passerines landing on a fixed or oscillating feeder. Aerodynamic braking is typically achieved in raptors through a rapid pitch-up manoeuvre executed at the end of a gliding approach. This manoeuvre produces high drag as predicted by published unsteady aerodynamic models, but unexpectedly the data shows no accompanying peak in lift. The complexity of wing-tail morphing and rotation during the rapid pitch-up manoeuvre points to the careful control of aerodynamic forces during unsteady deep stall.
A high degree of variation in the perching manoeuvre was evident in the Steppe eagle flights, likely in response to local air conditions. However the hawk flights were exceedingly consistent under the controlled experimental conditions. Different perch distances were used to induce variation in the hawks’ braking strategy. Braking was achieved in a flapping rather than gliding approach in the shortest flights, although the observed pattern of body pitch-up was consistent across flight distances. Systematic inter-individual variation was recorded in both wing motion and trajectory shape.
As a visually-guided flight behaviour, braking is controlled precisely with respect to the target such that the bird may land with low impact force and avoid injuries. Flights from the eagle and hawks show evidence for control of braking in line with the predictions of tau theory: during approach to the perch, both the rate of change in the optic flow variable tau and the rate of deceleration were constant. This was not the case for wild passerines using intermittent flight, although they might still use optic flow in feedback control.

Keywords: flight
motion capture
eagle
landing flight
flight control
bird flight
flight kinematics
Harris hawk
wing motion
flight mechanics
morphing wings
perching
Advisor: Taylor, G
Towards healthier diets and more sustainable food systems: Developing and evaluating behavioural interventions to reduce meat consumption

Producing meat generally leads to greater greenhouse gas emissions, deforestation, water use and pollution, and biodiversity loss compared to producing plant-based foods. While there are many supply-side measures that can help to mitigate livestock’s environmental impact, substantively reducing meat consumption is required to ensure that food systems can sustainably feed the growing global population and would result in some benefits for human health too. Behavioural interventions to encourage changes in eating habits could help to reduce meat intake, but few such interventions have been implemented and rigorously tested. The aim of this thesis is to contribute towards addressing this evidence gap by generating empirical evidence on the effectiveness of behavioural interventions to reduce meat consumption through (i) systematically reviewing and synthesising the evidence on the effectiveness of interventions targeting conscious behavioural determinants or restructuring physical micro-environments; (ii) the development of a novel behavioural intervention (Replacing Meat with Alternative Plant-based Products, RE-MAP) to reduce meat consumption through the provision of meat substitutes, infographics, success stories, and recipes; (iii) a randomised trial evaluating the impact of RE-MAP on meat consumption, wider dietary changes, markers of health risk, markers of environmental degradation, and psychosocial factors related to meat and meat substitutes consumption; and (iv) qualitative interviews exploring the mechanisms through which the intervention might have delivered impact and recipients’ experiences of the intervention. The results of my DPhil suggest that some behavioural interventions targeting conscious determinants of human behaviour and restructuring physical micro-environments can help to reduce meat consumption. Providing meat substitutes for four consecutive weeks along with supporting informational material is an acceptable strategy to help people eat less meat and emerged as one of the most effective interventions to reduce meat consumption tested to date. Specifically, RE-MAP led to a 63 g/d reduction in meat consumption at the end of the intervention and a 39 g/d reduction four weeks after the intervention completion. Based on these findings, future research should investigate how to translate the active components of the RE-MAP intervention into a scalable policy option.

Keywords: sustainable food systems
healthy diets
systematic review
meat consumption,
randomised controlled trial
behavioural science
Advisor: Jebb, S
Aveyard, P
Astbury, N
Cook, B
Sigma-hole non-covalent interactions in anion host-guest chemistry and the mechanical bond

This thesis describes the use of σ-hole interactions in acyclic, macrocyclic and mechanically interlocked receptors for anion recognition and sensing.
Chapter 1 provides an overview of the field of supramolecular host-guest chemistry with particular focus on host systems bearing σ-hole donor motifs for anion guest binding, followed by a discussion of mechanically interlocked host molecules for anion recognition and sensing.
Chapter 2 describes the synthesis of air and water stable acyclic tellurium and selenium-based chalcogen bonding receptors followed by an investigation of their thermodynamic anion binding properties in organic and mixed aqueous/organic solvent media. The integration of halogen bonding and chalcogen bonding motifs into mechanical interlocked molecular structural frameworks is also explored.
Chapter 3 details combining σ-hole donors and the BINOL motif to form chiral host receptors. The synthesis of a chiral halogen bonding [2]rotaxane structure is described as well as chiral acyclic and macrocyclic receptors possessing four integrated halogen bond-donors which are shown to be capable of binding chiral carboxylate anions. The enantioselective properties of these receptors were determined by monitoring the fluorescence changes of the respective receptor’s integrated BINOL or pyrene fluorophore upon chiral anion guest binding.
Chapter 4 introduces the use of halonium cation species in supramolecular chemistry. Primarily, this chapter investigates the stability of iodonium species in pyridyl-based pseudorotaxane assemblies and mechanically bonded [2]rotaxanes using NMR spectroscopy.
Chapter 5 summarises the conclusions of this thesis.
Chapter 6 describes the experimental procedures carried out in this work detailing characterisation of novel compounds presented in chapters 2-4. Additional information pertaining to crystallographic data and computational work are provided in the Appendices.

Keywords: Halogen Bonding
Supramolecular Chemistry
Intermolecular Interactions
Macrocycles
Rotaxanes and Catenanes
Mechanically Interlocked Molecules
Chalcogen Bonding
Host-Guest Chemistry
Advisor: Beer, P
Paperscapes: navigating books in Early Modern England

This thesis attends to the place of paper in early modern literature, both in actuality and in imaginary form. While a conventional set of (often gendered) tropes holds paper to be passive, blank, and static, these four chapters attend to texts and sites which resist those tropes, and which foreground paper’s role as an intellectual-material site that is both agentic and mobile. Paperscapes: Navigating Books in Early Modern England fuses literary scholarship, bibliography, and book history to engage with the affordances of paper as textual substrate and material form.
The structure of this thesis foregrounds paper on the move. The chapters focus on the paper volvelles that direct readers around George Wither’s Collection of Emblemes (1635), whose verse enables spiritual as well as bibliographic modes of navigation; on the stories that imprints tell about paper’s journeys through the city, which collide with the textual routes of James Howell’s Londinopolis (1657); on the moving sheets and books which trouble the rhetoric of Samuel Pepys’ aspirationally static library; and on the global narratives of circulation in which John Taylor’s The Praise of Hempseed (1620) implicates paper. Paperscapes takes its structure from actual sites through which paper moves – the book, the city, the library, and the globe – while simultaneously asserting that paper as substrate makes room for the texts in which imaginary journeys of readers and books play out. Reading early modern printed texts was and is to encounter paper in a contingent place and form. Noting both that paper moves around, and that place matters for how we read, this thesis argues that the mobility of paper has literary implications in unsettling the meaning of text. Paperscapes reverses the suggestion that ‘text is more legible than its substrate’, and provides a paper counterpoint to the codex which is grounded both in material readings and in the early modern imagination.

Keywords: paper
navigation
emblem
early modern
john taylor
volvelle
londinopolis
book history
renaissance
imprint
library
material texts
bookshop
samuel pepys
history of reading
print
Advisor: Smyth, A
Smith, O
Affect and materiality in therapeutic spaces. A contemporary archaeology of hospices.

Through a series of case studies I explore the affective impact of the therapeutic spaces of hospices on the communities they serve, their staff, volunteers and users. Hospices provide services for those with life-limiting conditions. Cure is not possible, the subjective wellbeing of patients and their loved ones is thus paramount. Hospices deliver a range of palliative care interventions but what distinguishes hospices is their buildings which have the potential to contribute to the enhancement of wellbeing. Drawing on Material Engagement Theory (MET), enactivist perspectives on affect, Heideggerian conceptions of dwelling, the philosophy of atmosphere, the theory of wellbeing and other resources I explore the therapeutic mechanism of hospice spaces. I argue that atmospheres are the affordances of Ingold’s “weather world” and are at least as important as the affordances of the object world. Therapeutic spaces exercise their agency through permutations of affordance and atmosphere which facilitate or constrain forms of affect/movement of the material and felt bodies of those who use the buildings.
I argue that through mechanisms of “enactive signification” hospice buildings mobilise the support of the communities they serve and concretise their identity. I suggest that changing regimes of clinical care are in unrecognised conflict with some aspects of the original philosophy of hospice care, which was closely aligned with Heidegger’s concept of “dwelling”, and that this conflict threatens the identity and sustainability of the hospice movement. I provide a number of illustrations of the ways in which aspects of design contribute to the experience of both hospice users and community and I make a number of suggestions as to how hospices could navigate the implications of changing regimes of care and how the differing functions of the hospice may be combined and facilitated by their design. This analysis of the relationship between mind and architecture opens an underexplored domain of research into MET, phenomenology, the extended mind and material agency with profound implications for the commissioners, designers and users of therapeutic spaces.

Keywords: Affect
Hospices
Material engagement theory
Homecoming
Wellbeing
Atmosphere
Architecture
Heidegger
Advisor: Malafouris, L
Factors and processes of educational and social stratification in Greece: the role of shadow education

This study examines the role of Shadow Education (SE) in the process of educational achievement in Greece, within an educational and social reproduction framework. It examines SE participation alongside a number of other SE characteristics both separately and within a series of models. The models address questions of SE’s relationship to both students’ background characteristics and their later achievement; their modal strategies for participating in SE, the overall role played by SE as a mechanism of educational and thus social reproduction, and the homogeneity of the effect of SE participation on students’ educational achievement. In order to do so, data was collected from 1508 students in the final year of Greek Upper Secondary school students using a single stage stratified cluster sampling technique, using a mail questionnaire.
The analyses suggested that SE Participation, and Group SE Participation in particular, mediate a portion of the significant effect of differential background characteristics on students’ Educational Achievement. Indeed, these effects were entirely mediated by students’ SE Quality and Student Effort.
Students’ modal strategies for SE participation appear to depend on what point in their academic careers they are examined. They go from mixed (i.e., both enhancement and remediation) in primary or early-secondary to purely enhancement oriented by upper-secondary education. Non-ethnically Greek students do not appear to benefit from SE participation; they also differ significantly in regards to the gender achievement gap and returns to student effort. In general, however, all students, from those most to those least likely to participate in SE seem to reap the same benefits from participation. Further evaluation of the models examined herein, including replication, measurement modification and use of longitudinal data is recommended to further elucidate the role of SE in the educational achievement process.

Keywords: Propensity Scores
Inequality
Causal Effects
Structural Equation Modeling
Remediation
Modal Strategies
Greece
Tutoring
Enhancement
Univeristy Entrance Exams
Private Tutoring
Ethnicity
Regression
Critical Transition Points
Heterogeneity of Effects
Stratification
Path Model
Gender
Shadow Education
Reproduction
Treatment Effects
Quantitative Analysis
Advisor: Breen, R
In search of lost time patterns. How class, gender and social contexts structure our daily lives

In this thesis, I investigate sequential patterns of time use in 23 countries during the period 1961- 2015, progressively moving down the level of analysis from a cross-national level to focus on the UK, and then on UK couples. This contribution to the literature comprises three empirical studies.
The first study explores the different daily time use sequences structuring 23 contem- porary societies across 50 years. The analyses reveal eight common everyday sequence patterns; including different paid work, unpaid work, and leisure clusters. This set of patterns shows similar distributions across the different countries and time periods. The second study investigates socio-demographic differences in time use patterns in the UK over the period 1983-2015. Important differences exist between men and women regarding the distribution of paid and unpaid work, and the time patterns of working class men and women are also very different from those of middle/upper class men and women. The social stratification of time use is also revealed by the unequal distribution of patterns between weekdays and weekends.
The last study explores gender inequalities at the level of couple time use patterns in the UK in 2015. I take an innovative approach by analysing diaries from partners of the same couple simultaneously. I find that, when together with their partner, men are much more likely to watch TV and enjoy leisure while women do domestic chores.
The thesis proposes new ways to explore time use diaries and contributes to several ar- eas of sociology, such as social stratification research and the domestic division of labour literature. The thesis concludes by reflecting on potential explanations as to why and how time use patterns can at the same time be highly stratified by class and gender while also being relatively stable across time and country.

Advisor: Sullivan, O
Gershuny, J
"I can't wait, honestly": How can Year 7 disadvantaged students be encouraged to raise their aspirations for higher education?

The persistent gap between university entry rates of disadvantaged students and their more-affluent peers, provides the focus for this practitioner research. Both nationally and at School X, fewer disadvantaged students are opting for higher education and this intervention aims to raise students’ awareness of university so they may aspire to follow this path in the future. Furthermore, the participants are from Year 7 to ensure this process begins as early as possible and can help inform their Key Stage 4 subject decisions, taken in Year 8. This account begins with an introduction followed by a critical, wide-ranging literature review, examining research around: the benefits of going to university; evidence for a participation gap between disadvantaged students and their more-affluent peers; factors influencing the participation of disadvantaged students in higher education, including an exploration of Bourdieu’s cultural reproduction theory; and the impact of widening participation initiatives. Contrary to some policy-makers and, indeed, my own assumption, the initial small-group interviews did not reveal a ‘poverty of aspiration’ amongst the 29 participants with the vast majority aspiring to go to university. Rather, an absence of accurate knowledge of higher education was exposed and then addressed through a number of awareness-raising interventions, including a series of workshops, devised and delivered in collaboration with the Education Liaison Officer (ELO) of a local university (University Y). A detailed account of the original methodology (Plan 1) is presented, followed by an alternative plan (Plan 2) created in response to the Covid-19 national ‘lockdown’. Findings suggest this collaboration has been successful in raising awareness of university among disadvantaged Year 7 students.
Furthermore, the project seems to have capitalised on the already-existing aspirations with one student stating, at the end of the project, “I can’t wait, honestly”.
Finally, the implications of this research are considered, including the two institutions agreeing to continue this partnership on a long-term, sustained basis and the development of the Key Stage 3 PSHE curriculum.

Keywords: Awareness
MLT2020
Disadvantaged
Higher Education
MLT
Aspiration