VictorJuiz/thesis huggingface dataset:
Investigating mechanisms of Epstein-Barr virus reactivation in epithelial cells
Keywords: Reactivation
EBV
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.
Regulation of the base excision repair pathway
Keywords: Sp1
XRCC1

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.
Restructuring in Slovene
Keywords: clitics
long distance dependencies
minimalism
restructuring
semantics
syntax
zero phase syntax

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.
Geometry of actions, expanders and warped cones
Keywords: Discrete Fundamental Group
Warped Cone
Approximating Graphs
Expanders
Coarse Geometry

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.
Vocabulary Explanations and Second Language Development in Adult Beginning-Level ESOL Classroom Interaction: A Conversation Analysis Perspective
Keywords: Vocabulary Explanation
Microgenetic Analysis
Conversation Analysis
ESOL Classroom Interaction
Sociocultural Theory
Second Language Acquisition

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.
A 230 GHz focal plane array using a wide IF bandwidth SIS receiver
Keywords: Focal plane array
Millimetre-wave astronomy
Star formation
Instrumentation
SIS mixer

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.
Class along the color line
Keywords: Affirmative action
Racial threat
Racial segregation
Welfare
Racial attitudes

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.
Natural convection in electrochemical systems
Keywords: natural convection

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.
Teaching mobile robots to use spatial words
Keywords: language and perception
situated interaction
spatial descriptions
perceptual grounding
dialogue
natural language semantics

The meaning of spatial words can only be evaluated by establishing a reference to the properties of the environment in which the word is used. For example, in order to evaluate what is to the left of something or how fast is fast in a given context, we need to evaluate properties such as the position of objects in the scene, their typical function and behaviour, the size of the scene and the perspective from which the scene is viewed.
Rather than encoding the semantic rules that define spatial expressions by hand, we developed a system where such rules are learned from descriptions produced by human commentators and information that a mobile robot has about itself and its environment. We concentrate on two scenarios and words that are used in them. In the first scenario, the robot is moving in an enclosed space and the descriptions refer to its motion (“You’re going forward slowly” and “Now you’re turning right”). In the second scenario, the robot is static in an enclosed space which contains real-size objects such as desks, chairs and walls. Here we are primarily interested in prepositional phrases that describe relationships between objects (“The chair is to the left of you” and “The table is further away than the chair”). The perspective can be varied by changing the location of the robot. Following the learning stage, which is performed offline, the system is able to use this domain specific knowledge to generate new descriptions in new environments or to “understand” these expressions by providing feedback to the user, either linguistically or by performing motion actions.
If a robot can be taught to “understand” and use such expressions in a manner that would seem natural to a human observer, then we can be reasonably sure that we have captured at least something important about their semantics. Two kinds of evaluation were performed. First, the performance of machine learning classifiers was evaluated on independent test sets using 10-fold cross-validation. A comparison of classifier performance (in regard to their accuracy, the Kappa coefficient (κ), ROC and Precision-Recall graphs) is made between (a) the machine learning algorithms used to build them, (b) conditions under which the learning datasets were created and (c) the method by which data was structured into examples or instances for learning. Second, with some additional knowledge required to build a simple dialogue interface, the classifiers were tested live against human evaluators in a new environment. The results show that the system is able to learn semantics of spatial expressions from low level robotic data. For example, a group of human evaluators judged that the live system generated a correct description of motion in 93.47% of cases (the figure is averaged over four categories) and that it generated the correct description of object relation in 59.28% of cases.
Perceptions of risks to elite secondary school education in South Africa
Keywords: South Africa Education
Elite Education
Education Risks

This study engages with the most important risks facing quality education in elite secondary schools in South Africa. It adopts a critical realist perspective that emphasises the importance of perceptions, as they shape the decisions and actions of those faced with risks. Through the use of surveys and in-depth semi-structured interviews, perceptions of a wide range of risks were explored: ranging from classrooms, to schools and their social contexts, to national and global political and economic factors. The perceptions of risks of different participants in this research varied considerably: with risk prioritisation tending to correspond to the risks a respondent was most directly dealing with. Several key risk themes emerged, including: the Middle Class squeeze; Race, Transformation and Political Vulnerability; Competition and the Neo-Liberal Order; Innovation and Change vs Continuity; and Fragmentation, Identity, and Social Capital. Further research is needed to aid decisions by practitioners around the specific requirements of 21st century education, as well as to find solutions to re-shape the political economy of quality teacher supply.
Priority-setting for malaria control and elimination in Myanmar
Keywords: Geographic targetting
Cost-effectiveness
Economic evaluation
Malaria

In Myanmar, Plasmodium falciparum malaria is important because of both the burden of disease and the emergence of parasites resistant to artemisinin-based therapies. In 2012, concomitant with the lifting of international economic sanctions, funding for malaria control and elimination in Myanmar rose significantly. The University of Oxford was asked to support priority setting by assessing the relative cost-effectiveness of insecticide- treated bed nets and community health workers, particularly with respect to planning in the Myanmar Artemisinin Resistance Containment region along the east of the country. In the context of rising artemisinin resistance and, later, the goal of regional malaria elimination by 2030, reduction in malaria transmission was an important consideration in prioritising between interventions.
A cost-effectiveness analysis was undertaken using both a static decision tree model and a dynamic disease transmission model. Supporting work towards this analysis included a systematic review of dynamic-transmission economic-evaluations and the creation of a data repository to collate governmental and non-governmental malaria case records. In addition, initially unplanned work on economic evaluation methodology was completed; identifying challenges in the application of cost utility analysis to this decision problem and proposing a framework for budget-based geographic resource allocation as an adaptation of standard methods.
The results of this work include a tripling of the number of malaria diagnostic reports available between 2012 and 2014 (71% increase in Plasmodium falciparum cases) with this data showing a decrease in Plasmodium falciparum cases over time, alongside rising testing rates. Cost utility analysis found that, in general, malaria community health workers are more costly yet more effective than insecticide treated bed nets, though in both cases cost effectiveness is very much context dependent. Geographic allocation analyses using both static and dynamic models illustrate the potential for economic evaluation to provide both more detailed and more practical policy recommendations. Parameter uncertainty was explored in both cases. Some township recommendations were robust to both parameter uncertainty and model variation (structural uncertainty). Viewed through the lens of the Reference Case for Economic Evaluation in Low and Middle Income Countries (published during the course of this DPhil), budget-based geographic resource allocation largely adheres to the healthcare economic evaluation principles and offers improvements to dealing with heterogeneity and resource constraints. This DPhil recommends that Myanmar malaria policy is tailored to reflect geographic variation in intervention cost-effectiveness, rather than focusing on universal coverage, and illustrates a framework for economic evaluation to support budget-based geographic allocation.