VictorJuiz/thesis huggingface dataset:
Investigating mechanisms of Epstein-Barr virus reactivation in epithelial cells

Approximately 10% of all gastric cancer cases worldwide are associated with Epstein-Barr virus (EBV) infection. This subgroup differs from non-infected equivalents through a distinct mutational and epigenetic signature, which is crucial for the establishment and maintenance of the viral latent state. Disruption of the latent state and subsequent induction of the lytic cycle, called reactivation, can be used as a therapeutic strategy for this cancer type through either combination with antiviral agents or by induction of an EBV-specific immune response.
In this study, epigenetic inhibitors were tested for their potential to reactivate EBV using a novel screening method based on the expression of Zebra, a key regulator of EBV reactivation. Histone deacetylase inhibitors (HDACis), more specifically benzamide-based HDACis, were the most potent group of reactivating agents in this screen. Those HDACis induced the expression of lytic cycle genes as well as targeted cell killing in combination with antiviral agents. Moreover, the reactivation through those agents was sufficient to activate cytotoxic T-cells and thereby ensured a supportive role of the immune system in targeted cell killing. In an additional screen, topoisomerase inhibitors and other chemotherapeutic agents showed synergistic effects on Zebra expression together with HDACis, which was linked to the induction of p53 expression through those compounds. While p53 is known to be involved in the expression of Zebra, the viral DNA processivity factor Ea-D and the viral DNA binding protein DNBI were identified as a potential novel binding protein of p53 and could thus point towards a novel role of p53 in EBV lytic replication.
Taken together, this study identifies potential novel therapeutic compound combinations for the treatment of EBV-associated epithelial cancers that could be translated into the clinic after further assessment.

Keywords: Reactivation
EBV
Epithelial cells
Advisor: Lu, X
Chemical analysis of biomarkers and silver nanoparticles

This thesis is focused on the development of chemical sensors for the detection of molecular biomarkers and silver nanoparticles, and the application of the techniques to authentic saliva samples.
As an important antioxidant in humans, the first aim of this thesis is to develop sensors for the detection of glutathione. Two different assays for glutathione detection based on electrochemical and spectrophotometric techniques are developed. The spectrophotometric assay is further applied to authentic human plasma and saliva samples, where the stability of glutathione is investigated in-vitro. The copper(II)-catalysed oxidation process which is the major cause of the loss of reduced glutathione from biological samples is next investigated and the mechanism is proposed. The spectrophotometric glutathione assay is then employed to study the potential of salivary glutathione as a biomarker for bipolar disorder.
An electroanalytical assay is also developed for the detection of salivary uric acid, a potential biomarker for gout, oral cavity cancer and other several diseases. The significantly different electrochemical behaviour in authentic as compared to synthetic saliva of commonly used redox mediators such as ferrocenemethanol and ferrocyanide is further highlighted in this thesis.
In addition to molecular biomarkers such as glutathione and uric acid, an electrochemical sensor is developed for the detection of ensembles and individual silver nanoparticles (AgNPs). The oxidative dissolution of AgNPs is first investigated by two electrochemical techniques: nano-impacts and anodic stripping voltammetry, where the results reveal the relative kinetics of the process. The electrochemical techniques are then directly applied to investigate the physicochemical properties of AgNPs in authentic human saliva.

Advisor: Compton, R
Regulation of the base excision repair pathway

Maintenance of genomic stability is paramount for survival of an organism; failure to repair DNA damage ultimately leads to the accumulation of genetically unstable cells and the onset of different human diseases including cancer. DNA single strand breaks and base oxidation/alkylation are among the most frequent types of DNA damage occurring spontaneously in cells. Base excision repair (BER), which copes with the majority of these lesions, is therefore a fundamental DNA repair system. Accordingly, it is important to understand how BER is regulated, and particularly, how and if BER is affected by the cellular load of DNA damage.
Although functions of key BER proteins are well-defined, regulation of their expression is poorly understood. During BER, the protein XRCC1 is particularly important. It functions as a scaffold, stabilising repair complexes at sites of DNA damage thereby promoting efficient DNA repair. As a central coordinator in BER, it is therefore of great interest to understand how expression of XRCC1 is controlled. In this thesis I demonstrate that modulation of XRCC1 expression is mediated by transcription factor Sp1.
Importantly, Sp1 is also affected during the DNA damage response, suggesting an indirect mechanism promoting BER modulation in response to the cellular DNA damage load. In fact, I show that, in response to persistent DNA strand breaks, the key DNA damage signalling factor ATM phosphorylates Sp1. This initiates Sp1 degradation, negatively affecting BER. Therefore, this thesis identifies a mechanism involving signalling from ATM that regulates BER in response to persistent DNA damage, which I link to susceptibility to apoptosis and cell elimination.
I hypothesise that regulation of DNA repair in response to persistent DNA damage constitutes a mechanism to promote the elimination of potentially pre-cancerous cells that accumulate unrepairable levels of DNA lesions.

Keywords: Sp1
XRCC1
Advisor: Dianov, G
Exploring the role of religious faith in distinguishing Christian faith-based organisations from secular NGOs working with women and children in Cambodia

Faith-based organisations (FBOs) and secular non-governmental organisations (NGOs) are significant service providers in the developing world, yet limited research has systematically compared these organisations. Adding knowledge to the field about the faith-based and secular actors implementing social policy, this thesis explores the extent to which, and why, religious faith might distinguish Christian FBOs from secular NGOs. It elucidates this by comparing organisations working with women and children in Cambodia who have been sexually trafficked, abused, or involved in the sex trade.
Analysing data from thirteen Christian FBOs and twelve secular NGOs, including from interviews, websites and organisational documents, this study examines the ways in which religious faith in FBOs distinguished their: 1) goals and missions, 2) motivations, 3) approaches to care, and 4) conceptions of success—areas of research that have had limited exploration in a development context. An existing typology is built upon and operationalised in the study that, in particular, de-complexifies the process of categorising FBOs and allows for more accurately classifying secular NGOs.
Faith was found to distinguish FBOs from secular NGOs in all four of the dimensions comparatively examined in this thesis. The findings illuminate the ways in which FBOs understood and integrated faith in their organisations, providing a richer understanding of the role of religious faith in FBOs. It is argued that the contrasts between the two types of organisations, in terms of faith, relate to both the infusion of faith in FBOs and the development context in which they work—a concept referred to here as Context-Infusion Convergence. This theory ensures the study’s wider significance, providing an avenue for future comparative research on FBOs and secular NGOs in other geographical locations.
This thesis thus empirically examines the extent to which faith may distinguish FBOs from their secular counterparts and provides theoretical insight about why these differences may exist. Doing so, it adds to knowledge about religious faith in FBOs and in the study of social policy.

Advisor: Bennett, F
Restructuring in Slovene

In Slovene, as well as other languages, two types of infinitival constructions containing a matrix and a complement verb are observed: in some cases each verb projects in an independent locality domain, in others, both verbs are a part of the same domain (restructuring). This is confirmed by processes such as clitic climbing, non-focus scrambling, long-passive, and the scope of adverbs and negation. Restructuring was analysed in every theory of generative syntax. This article challenges these analyses and provides a new analysis based on the theory of lexical or first phase syntax. These theories of lexical decomposition argue that a substantial part of semantics of verbal predicates, their argument and event structure, is built by syntactic templates. Examining the data from Slovene, the article concludes that the chosen frameworks provide a better account of syntactic and semantic properties of restructuring and non-restructuring configurations.

Keywords: clitics
long distance dependencies
minimalism
restructuring
semantics
syntax
zero phase syntax
Advisor: Ramchand, G
Geometry of actions, expanders and warped cones

In this thesis we introduce a notion of graphs approximating actions of finitely generated groups on metric and measure spaces. We systematically investigate expansion properties of said graphs and we prove that a sequence of graphs approximating a fixed action ρ forms a family of expanders if and only if ρ is expanding in measure. This enables us to rely on a number of known results to construct numerous new families of expander (and superexpander) graphs.
Proceeding in our investigation, we show that the graphs approximating an action are uniformly quasi-isometric to the level sets of the associated warped cone. The existence of such a relation between approximating graphs and warped cones has twofold advantages: on the one hand it implies that warped cones arising from actions that are expanding in measure coarsely contain families of expanders, on the other hand it provides a geometric model for the approximating graphs allowing us to study the geometry of the expander thus obtained.
The rest of the work is devoted to the study of the coarse geometry of warped cones (and approximating graphs). We do so in order to prove rigidity results which allow us to prove that our construction is flexible enough to produce a number of non coarsely equivalent new families of expanders. As a by-product, we also show that some of these expanders enjoy some rather peculiar geometric properties, e.g. we can construct expanders that are coarsely simply connected.

Keywords: Discrete Fundamental Group
Warped Cone
Approximating Graphs
Expanders
Coarse Geometry
Advisor: Drutu, C
Vocabulary Explanations and Second Language Development in Adult Beginning-Level ESOL Classroom Interaction: A Conversation Analysis Perspective

A small body of recent research on vocabulary explanations (VEs) in second language (L2) classrooms (e.g. Mortensen, 2011; Waring et al., 2013) has attempted to provide the sequential descriptions of the key elements of VEs and investigate how teachers draw on their linguistic and semiotic resources to construct the VE sequences (e.g. Smotrova and Lantolf, 2013). Nevertheless, more work is needed in order to allow educators to better understand how VEs are provided in L2 classrooms. In particular, there is a shortage of studies (e.g. Tai and Brandt, 2018) illustrating the nature of VEs in beginning-level English for Speakers of Other Languages (ESOL) classrooms, where learners all share different first languages (L1s) and have limited English proficiency. Moreover, the shared linguistic resources between the teacher and learners are typically limited in beginning-level ESOL classrooms. To date, there is no longitudinal study which will allow for tracking the impact of VEs on contributing to learners' conceptual understandings of the meanings of target vocabulary items. The vast majority of the studies, which identified learners' display of understanding of L2 word meanings in classroom interactions, were based on one-off analyses of the classroom discourse (e.g. Waring et al., 2013). This prevents educators and researchers from observing the learner's change of conceptual understandings over time. This MSc dissertation contributes to the identified research gaps by employing Conversation Analysis (CA) to 1) investigate the nature of VEs in a beginning-level ESOL classroom and 2) conduct a 4-month longitudinal analysis to explore the potential for employing CA as the methodological tool for tracking learners' development of the conceptual understandings of the meanings of particular vocabulary items which are previously explained. The classroom data is taken from a corpus of video-data collected in a beginning-level adult ESOL classroom in the United States. The key findings demonstrate that other than verbal 3 resources, teacher's use of embodied resources in explaining vocabulary items in the classroom plays an important role in facilitating the learners' understandings of the meanings of different vocabulary items. The learner's use of gestures allows her to externalise her understandings of the L2 word meanings and also allows teachers to evaluate the learner's current knowledge states. These findings also suggest that CA provides some, albeit incomplete, evidence of the learner's developing conceptual understandings of L2 word meanings and it allows researchers to investigate how these developmental changes occur in each interactional context of L2 vocabulary use.

Keywords: Vocabulary Explanation
Microgenetic Analysis
Conversation Analysis
ESOL Classroom Interaction
Sociocultural Theory
Second Language Acquisition
Advisor: Macaro, E
Khabbazbashi, N
A 230 GHz focal plane array using a wide IF bandwidth SIS receiver

Superconductor-Insulator-Superconductor (SIS) mixers offer the best noise properties of any heterodyne mixing technique at millimetre wavelengths. In astronomy, they are used for sensitive spectroscopy, which is vital for understanding the properties of the cold interstellar medium, including regions of star formation activity. Modern SIS receivers have noise properties that are &Tilde;3 times the quantum limit, and it is now becoming increasingly difficult to lower the noise properties any further. In this thesis, I investigate two techniques that extend the capability of SIS receivers.
The first technique is extending the instantaneous bandwidth of the receivers, i.e., the intermediate frequency bandwidth (IFBW). For spectral line sources, wide IFBW expands the survey depth to allow multiple emission lines to be observed simultaneously. Here, I present a new SIS mixer device at 230 GHz. The planar circuit was minimised to reduce any parasitic capacitances that may limit the IFBW. Experimentally, the device provides excellent noise temperatures down to 36 K and an IFBW extending from approximately 0–11 GHz. Simulation software was developed to better understand the performance of this device, and it suggests that the IFBW can be extended to higher frequencies if the IF measurement chain is upgraded.
The second technique that I investigate is increasing the number of receivers in the focal plane of the receiver, i.e., adding more pixels. There are many challenges involved in this task including how to fit multiple receivers into a small space, how to properly cool the receiver, and how to deliver the local-oscillator signal. Here, I present a new 1 × 4 focal plane array. This array is acting as a demonstrator for a new array architecture that can be expanded into many more pixels in the future. It uses cascaded waveguide power splitters to divide the local-oscillator signal, and then waveguide directional couplers to combine the LO with the astronomical signals.
Finally, I present CO(J=1→0) measurements from 34 galaxies in the 5MUSES survey. These measurements trace the amount of cold molecular gas present in these galaxies. By comparing these measurements to other metrics that trace star formation activity (e.g., infrared luminosity), I was able to form empirical relationships between the observed quantities. I also combined these results with other star formation studies from nearby and high redshift galaxies to form scaling relationships spanning a large fraction of cosmic time.

Keywords: Focal plane array
Millimetre-wave astronomy
Star formation
Instrumentation
SIS mixer
Advisor: Yassin, G
Numerical methods for simulating dilute polymeric fluids

Navier--Stokes--Fokker--Planck systems are coupled systems of partial differential equations arising from statistical physics as mathematical models of dilute polymeric fluids. The solvent is assumed to be a viscous incompressible Newtonian fluid, whose evolution in time is modelled by the Navier--Stokes equations; the elastic effects exhibited by the dilute polymeric fluid are modelled by the elastic extra stress tensor, whose spatial divergence appears on the right-hand side of the Navier--Stokes momentum equation. In this thesis we investigate and implement several numerical methods for the computational simulation of dilute polymeric fluids. The Fokker--Planck equation featuring in the model is a high-dimensional transport-diffusion equation, whose numerical solution by conventional means is extremely challenging since standard numerical methods applied to this equation suffer from the curse of dimensionality. The key objective of the thesis is therefore to develop an efficient numerical approximation scheme for the model, where deterministic approximation techniques for the Fokker--Planck equation are replaced by a multilevel Monte Carlo method. Under suitable assumptions, we can prove exponential convergence in time of the solution to an equilibrium solution: the Maxwellian of the model. At the end of the thesis we perform a series of numerical experiments, including multi-bead simulations for polymer molecules modelled as bead-spring chains, with FENE-type (finitely extensible nonlinear elastic) spring potentials, to explore the practical performance of the proposed numerical method.

Advisor: Suli, E
Class along the color line

This thesis traces the contours of the Black-White color line in modern America by illuminating how Whites’ racialized political behavior varies across local geographic contexts.
In a critical reinterpretation of the racial threat hypothesis, I argue that local geography conditions the relationship between Whites’ racial orientations and their preferences on policies related to race—but not because Whites are passively threatened in proximity to a Black population. Rather, Whites are active, subjective perceivers of their surroundings who have an interest in maintaining their racial privilege. This conceptual shift not only challenges the assumed neutrality of Whites’ vision; it also enables me to identify the range of contextual indicators that Whites might construe as threatening, and the range of White attitudes that are activated as a result.
My empirical evidence comes from three case studies. The first two use geocoded survey data to analyze White opinion on welfare spending in 2000, and on affirmative action between 2006 and 2010. The third study draws on in-depth interviews conducted in 2016, exploring an issue related to school desegregation in Louisiana. Each study affirms the core findings of the thesis: Whites’ policy preferences are polarized according to racial orientations in settings where race is salient; and a shared White perspective is evident even across polarized attitudes.
My findings offer hope, showing that a sign of threat to some Whites may activate racially tolerant behavior in others; as well as reason to restrain our optimism, challenging the assumption that affluent Blacks, unlike the “undeserving” Black poor, will not be perceived as threatening by Whites. Ultimately, only by recognizing the color line’s responsiveness to local geography—and its resilience even as White attitudes liberalize and Black class positions improve—can we understand the line’s persistence or the possibility of one day dismantling it.

Keywords: Affirmative action
Racial threat
Racial segregation
Welfare
Racial attitudes
Advisor: King, D
Ansell, B
Natural convection in electrochemical systems

This thesis is concerned with modelling natural convective flows and specifically with their role in electrochemistry. The studies described here demonstrate that many electroanalytical techniques are prone to non-negligible natural convective effects, thus making the standard assumption for purely diffusional mass transport inapplicable. The chosen approach focusses on investigating idealized systems and establishing orders of magnitude for the quantities of interest. The complexity of the observed natural convective flows and their strong dependence on factors such as container geometry serve as compelling arguments for rigorously excluding natural convection in experimental measurements.
The text is structured as follows. Chapter 1 introduces the theoretical framework used in the rest of the text and gives an outline of the electrochemical techniques to which the results in later chapters apply. Chapter 2 surveys the literature on natural convection in electrochemistry and emphasizes recent developments. Chapter 3 studies the natural convection induced by the intrinsic heat of an electrochemical reaction, specifically its effect on mass transport in chronoamperometry and cyclic voltammetry. Chapters 4-6 deal exclusively with coupled heat and momentum transport. Chapter 4 considers the thermal convective flows that arise in an idealized cell for scanning electrochemical microscopy (SECM) and the surrounding air under conditions of imperfect thermostating. Chapter 5 is dedicated to thermal convection in an SECM cell that is being thermostated from below through a solid substrate. This chapter demonstrates the influence of the spatial distribution of substrate thermal conductivity on the observed flows and highlights this effect by using a simpler model of the SECM cell than Chapter 4. Chapter 6 investigates the thermal convection in a novel thermostated cell for electrochemical measurements. Chapter 7 contains the main conclusions from the studies described in the thesis. Appendices A, B and C provide additional data for Chapters 3, 5 and 6, respectively.

Keywords: natural convection
Advisor: Compton, R