VictorJuiz/thesis huggingface dataset:
Magnetic resonance imaging of cerebrovascular anatomy and physiology at 7 Tesla

Magnetic Resonance Imaging (MRI) can study the cerebrovasculature non-invasively in humans. It can image the vascular anatomy, as well as functional attributes such as flow and perfusion. This multi-modal capability renders MRI one of the most favourable imaging techniques to study the cerebrovasculature in research and in clinical settings.
The advent of human 7 Tesla (7T) MRI offers further benefits to existing methods. Most evidently, the higher signal-to-noise ratio (SNR) can be used to improve resolution. However concomitant changes in contrast mechanisms, an increase in the specific absorption rate (SAR) and transmit B1-field inhomogeneity need to be addressed when transitioning to higher field. Vessel wall imaging (VWI) is an exemplar application that benefits from higher resolution but is based on SAR intense methods. In the first part of this thesis the implementation of a VWI method, DANTE-SPACE, is described. The readout scheme was specifically optimised for high resolution wall depiction and enhanced suppression of cerebrospinal fluid to produce vessel wall contrast in the major intracranial arteries at 7T.
Besides refining spatial scales, recent technical developments have accelerated information content in the temporal domain. In-slice acceleration and simultaneous excitation of multiple slices substantially reduced acquisition times for many applications. In particular, multiband techniques have pushed sampling speeds in functional MRI (fMRI) to sub-second regimes. Traditionally, fMRI is used to study low frequency neuro-vascular signals below 0.1Hz. Aliases of cardio-respiratory-induced signals have been regarded as "physiological noise". Sufficiently fast sampling resolves the spectrum beyond the cardiac frequency, thus transforming noise into valuable signal. In the second part of this thesis strategies to map and quantify signal fluctuations at the cardiac frequency are described using echo-planar imaging (EPI). Potential age-related difference in the cardiac EPI signal power were studied. Also, an investigation was made into the underlying MR-mechanisms that form these fluctuations by decomposing the EPI-signal over the cardiac cycle into S0 and T2&ast; waveforms. Ultimately this research aims to foster the understanding of the vascular origins of cardiac-induced EPI signals. This will hopefully serve future research into how EPI data can be exploited to study cerebrovascular properties in healthy and diseased states.

Advisor: Jezzard, P
Recognition of noncanonical poly(A) sites in human genes

Cleavage and polyadenylation are essential pre-mRNA maturation reactions for almost all eukaryotic mRNAs. Noncanonical poly(A) sites are frequently present at proximal sites during alternative cleavage and polyadenylation. These sites are involved in the regulation of gene expression. This project aims to elucidate the mechanism of noncanonical polyadenylation.
Two noncanonical poly(A) sites JUND and ARAF have been investigated. Analysis of the sequence requirement of the AGUAAA poly(A) site in JunD reveals that, besides the core sequence element, a U-rich element (adU-rich) is required for optimal usage and the distance between AGUAAA and this element is important; Similar to MC1R, the ARAF poly(A) site has a degenerated poly(A) signal and it has been suggested to require a distant auxiliary element, possibly G-rich enhancer, for optimal poly(A) site usage.
With regard to trans-acting factors, WDR33 appears to be important for the recognition of sub-optimal JunD poly(A) sites, whereas CPSF30 and CPSF160 preferentially recognise the canonical poly(A) site over a weak poly(A) site in JunD-MC4R 3' end formation. Contrary to the current models, depletion of CFIm68 does not favour proximal noncanonical poly(A) site usage in our JunD-MC4R Mini-gene system, but instead reduces the usage of the distal site and generates read through transcripts. Finally, we find that whilst WDR33 and CPSF30 affect poly(A) site selection in JunD-MC4R plasmids, they globally do not show general preference for either canonical or noncanonical sites.
In summary, we investigate the architecture of ARAF and JunD poly(A) sites. We conclude that in both cases the strength of the poly(A) site is determined by the complex architecture of the poly(A) sites rather than the core sequences. Recognising the wider architecture of poly(A) sites will be essential to fully understand what constitutes a strong poly(A) site and how this can be modulated, in particular in the context of alternative cleavage and polyadenylation.

Advisor: Furger, A
Personalised search for the Social Semantic Web

Recently, the Web has been changing more and more to what is called the Social Semantic Web. As a consequence, the ranking of search results no longer depends solely on the structure of the interconnections among Web pages.
In my research, I argue that such ranking can be based on user preferences from the Social Web, and on ontological background knowledge from the Semantic Web. Therefore, I combine preference representation languages with Semantic Web technologies.
There is some related research in database community that had dedicated some time to integrate preferences in database queries. However, one cannot directly use the ideas from databases, as we additionally have ontological knowledge, which may introduce unknown values, so-called nulls. Therefore, I need to define the exact semantics and check their feasibility for this context.
In my thesis, as a first step towards closing the gap between the Semantic Web, databases, and preferences, I introduce families of expressive extensions of Datalog± with preferences as new paradigms for query answering over ontologies. I first define the syntax and semantic of the proposed frameworks, then propose top-k query answering algorithms under user preferences in semantic data for different types of queries and preference models. Each of the proposed frameworks comes with advantages and disadvantages; therefore, I provide formal properties of my algorithms and empirical experiments on the performance and quality of my results.
Furthermore, I explore the combination of my framework with uncertainty and the generalisation to the preferences of a group of users, where I analyse properties of my algorithms related with social choice theory.

Advisor: Lukasiewicz, T
New contradictions: the activism of middle-class youth in Delhi

This thesis examines forms of activism among middle-class youth in the context of neoliberal urban change in Delhi. The research is set within four interdisciplinary bodies of literature reflecting the experiences of young activists: middle-class identity, everyday politics and new modalities of social action, intersectionality, and active citizenship. What emerges from each of these bodies is a view to the contradictory politics of the young middle-class. Focusing on new forms of social action at the community level, this thesis uses an expansive definition of both activism and middle-class to encompass a range of activities from social enterprise, to technology-enabled mobilization around social issues, to political campaigning among India’s expanding middle-class. The research is framed within young peoples' period of waiting: for full adulthood, marriage, and importantly, full-time employment.
Grounded in qualitative fieldwork, this thesis concentrates on young people, aged 18 to 30, in the middle-class with putatively distinct activist practices. Young people in Delhi are engaged in various activities that loosely correspond to different ideals of social justice or social work. I illustrate the innate differences in these ideals, their motivations, and methods. I analyze the limitations of different activist projects and the extent to which the social action is constructive—in the sense of enhancing the capabilities of marginalized sections of society and promoting inclusivity. The young people at the core of this project contend to be anti-politics, yet they are quite political. Additionally, the interlocutors show contempt for the state and the commercial interests of the market but deploy and rely on strategies from both.
My examination gives prominence to the improvised nature of young people's lives and the decisions they make at key life stages. Activation of the self, and actualization for the researched youth, manifests in entrepreneurial activity, community work short of politics, and the negotiation of class, caste, and gender on an everyday basis.
This thesis argues for more scholarly attention to the everyday lives of middle-class youth that can offer insights into this key demographic and connect individual decisions to broader social and political change.

Keywords: Youth activism
Delhi
middle class
Advisor: Jeffrey, C
Mobile English language learning for youth empowerment: an action research study in Dharavi, Mumbai

With reach of the mobile phone in the developing world unsurpassed by any other form of information communication technology, and its potential as a means to support learning widely recognised and the subject of a range of exploratory interventions, researchers, policy makers and practitioners have turned to the challenges of making mobile learning initiatives more scalable, more sustainable and more sensitive to the needs and circumstances of learners. At the same time, there is a call for a critical approach to the use of technology that serves to expose immanent knowledge and to challenge unequal power relations within educational settings, in order to identify ways in which educational technologies can be used in fairer and more equitable ways.
This study employs action research, a methodological approach that I argue is appropriate for to address such an agenda. This thesis sets out the study of collaborative attempts to design and implement a mobile English language learning resource in partnership with a Non- Governmental Organisation (NGO) in Dharavi, Mumbai. Through three iterative action research cycles, conducted in a participatory manner with NGO leaders, teachers and students, this study investigates how the use of a mobile learning resource can provide a sustainable means of enhancing the learning of disadvantaged young adult participants enrolled on the NGO’s Youth Empowerment Program.
The design and use of a mobile learning resource is framed against a complex picture of young people's access, ownership and engagement with mobile technology, closely linked to gender, life stage and economic circumstance; as well as the NGO's shifting English language curriculum priorities and strategic change. The study reflects upon the nature of student learning experiences, through the use of the activities within the mobile learning resource itself, through broader strategies of digital engagement and through the participatory research process. Finally, the study identifies issues that constrain the sustained use of the mobile learning resource, including lack of flexibility and control over pedagogical content and the absence of continuing technical support.

Advisor: Davies, C
Eynon, R
Transcriptome dynamics of the suprachiasmatic nucleus and associations with psychiatric disease

The mammalian suprachiasmatic nucleus (SCN) drives daily rhythmic behaviour and physiology, yet a comprehensive understanding of its coordinated transcriptional programmes is lacking. Furthermore, there has been a long-standing association between circadian disruption and psychiatric disease, whose mechanism underpinnings are unknown. To analyse in detail the circadian transcriptome of the mammalian SCN and its variation in psychiatric disease, whole transcriptome sequencing (RNA-seq) of the mouse SCN was performed over a 24-hour light / dark cycle in both wild-type and blind-drunk (Bdr), a mutant strain for Snap25 that shows both schizophrenic endophenotypes and abnormal circadian behaviours.
2,648 novel intergenic long non-coding RNAs were identified using the SCN RNA-seq data, together with novel exons of annotated protein-coding genes, including the clock gene Cry1. Furthermore, in addition to identifying 4,569 genes which exhibited a classic sinusoidal expression signature, co-expression network analysis identified a group of 766 genes which unexpectedly peaked twice, near to both the start and end of the dark phase; this twin-peaking group is significantly enriched for synaptic transmission genes that are crucial for light-induced phase-shifting of the circadian clock. This twin-peaking module is also dysregulated in Bdr, which may provide clues to the molecular pathways linking circadian disruption with psychiatric disease.
These findings offer novel insight into SCN biology and suggest that transcriptional timing in the SCN contributes to gating clock resetting mechanisms which, when disrupted, may play a role in psychiatric disease.

Advisor: Ponting, C
Davies, K
A study of human monoclonal antibodies to influenza and ebola viruses

This thesis describes an analysis of the B cell repertoire in humans in response to infection or vaccination with Influenza or Ebola. We isolated monoclonal antibodies (mAbs) from individuals using single B cell cloning and PCR technology, and defined their epitopes, binding characteristics and neutralisation properties.
As summarised by Thomas Francis in 1960, we found that the secondary B cell response to Influenza is largely determined by the primary response to the virus that the donor was exposed to in childhood. In some individuals this can lead to focusing of the polyclonal antibody response to a single site on the influenza haemagglutinin. Monoclonal antibodies isolated from such focused responses selected escape mutations in vitro that matched actual antigenic drift observed in circulating viruses. Recapitulation of antigenic drift in vitro with human mAbs, in parallel with standard analysis with ferret anti-sera, may contribute to improved selection of vaccine strains by the WHO.
A second consequence of preferential selection of B cell responses from memory cells laid down early in life, is the expansion of broadly cross-reactive clones during exposures to viruses that are only distantly related to the original stimulus. We have isolated many protective antibodies to conserved epitopes on both haemagglutinin and neuraminidase from individuals with appropriate exposure histories. One novel antibody binds to the conserved active site of neuraminidase. Antibodies of this type may have therapeutic potential to complement antibodies to the conserved stem of Haemagglutinin.
In contrast to Influenza, the antibody response to the Ebola glycoprotein (GP) in vaccinated humans was essentially primary. The elicited antibodies were closer in sequence to germline than those to Influenza, and contained fewer somatic mutations. The response was more diverse, employing a wide selection of VH/L genes, and was directed at multiple epitopes in at least three distinct regions on the GP. Despite these features, half of the antibodies neutralised an Ebola surrogate virus in vitro, and many were therapeutic in a murine infection model. We developed a cocktail of antibodies to three non-overlapping sites for testing as a therapy in a stringent model of Ebola infection in the guinea pig.
Taken together our results fit with a Darwinian model of selection of the fittest B cells in the germinal centre reaction, where memory cells have a selective advantage over naïve B cells.

Advisor: Townsend, A
Rethinking materialism: a question of judgements and enactments of power

This thesis traces the etymology of 'materialism' using a Foucauldian discourse analysis to bring to the fore the word’s use as discursive mode of power. Through examining over 5000 texts, spanning across 400 years, I trace a line from the origins of materialism in philosophical thought of the Renaissance and Enlightenment eras to its uptake in American rhetoric and integration into the consumer behaviour literature.
This approach leads to a reconceptualization of materialism. Commonly viewed in consumer studies as a measurable value, trait, or motive inherent in the consumer, I situate materialism as external to the consumer. The word’s history, especially in consumer studies, demonstrates that it embodies moral condemnations.
I find that accusations of materialism rise in discourses during moments of intense social dislocations. It is wielded by social groups as part of a play for status. In this analysis, concepts of power as per Foucault and social distinctions as per Bourdieu, are used to explain the motives residing behind the use of the word. These motives, which reflect sociocultural dynamics and geo-political agendas, manifest in the meanings attributed to 'materialism', and the directionality of the allegation.
Thus I argue that 'materialism', at its essence, is an epithet used to advance or demobilise a set of interests. This is what I term, delegitimizing discourse—words used to debase other social groups. Studying 'materialism' as a case in point, I note that groups use delegitimizing discourse either an assimilative measure—rhetoric geared towards indoctrination—or as a defensive mechanism—rhetoric used to debase threatening elements and behaviours.
It is hoped that this new perspective will encourage academics to be rethink their approach to studying materialism, or in the least, to be aware of what is being measured, and what moral judgements and interests they are perpetuating through their continued studies.

Keywords: French materialist
Consumerism
power
etymology
social stratifications
Enlightenment philosophers
Foucauldian discourse analysis
American history
Materialism
Advisor: Scott, L
Spatial cognition in three-dimensional environments

Animals must navigate between different locations if they are to gather enough resources to survive. The natural world is three-dimensional; however, recent findings from studies of three-dimensional spatial cognition indicate that surface-bound animals remember information derived from the vertical dimension with lower accuracy than information from the horizontal dimensions. In contrast, non-surface-bound swimming and flying animals have been shown either to remember both with similar accuracy, or in some cases, remember vertical information more accurately than horizontal information. This has prompted questions about (i) the factors influencing spatial cognition in animals with different movement ecologies and (ii) what cues non-surface-bound animals use for navigation in three dimensions. In this thesis I explore these questions, principally through behavioural observations of freely-swimming fish in the laboratory. My findings reveal that factors influencing spatial cognition include (a) a difference in cues available in the vertical and horizontal dimensions, (b) asymmetry in the energetic costs of vertical versus horizontal travel and (c) animals’ ecological niches. The influence of movement ecology on spatial cognition is complex: in spite of moving principally in the horizontal dimensions, benthic fish preferentially use vertical cues when information derived from the vertical and horizontal dimensions conflict. Hydrostatic pressure varies linearly with depth and represents a stable and reliable cue in an often-variable environment, thus fishes' sense of pressure could explain their vertical preference. Finally, in the absence of information about pressure and over small distances, fish may use horizontally- and vertically-arranged visual landmarks as approximate guides rather than indicators of the exact position of a location. Taken together my results provide new insight into the mechanisms underlying fishes' navigation in three dimensions and shed some light on how evolutionary history and day-to-day movement contributes to spatial cognition.

Advisor: de Perera, T
Investigation of sugar-membrane vaccine stabilisation for improved vaccine thermostability and delivery

Vaccines and other biomolecules need to be maintained at specified storage temperatures from manufacture through to their end user. To satisfy this requirement an enormous network of fridges and freezers called the "cold chain" throughout the world must exist. This network may account for up to 80% of the total cost of vaccination and is susceptible to failure causing loss of vaccines. Stabilisation strategies for vaccines available in the literature have been limited to a few techniques for a few vaccines. To address this problem a novel, cost-efficient, and simple sugar-membrane technology has been developed. Sugar-membrane technology involves desiccation of biomolecules formulated in stabilising sugars in a fibrous matrix and has previously been demonstrated to thermostabilise live viral vectored vaccines exposed to extremes of temperature for prolonged periods of time.
The thesis investigates the applicability of the technology in stabilising a wide range of vaccines. The data reported demonstrate the effectiveness of the technology in thermostabilising the vaccines irrespective of the intrinsic complexities and thermo-sensitivity of the initial product. In addition, the thesis also studies the applicability of the technology in thermostabilisation of vaccines of veterinary importance. An accelerated stability study of sugar-membrane thermostabilised veterinary vaccines also demonstrated that the data are superior to those reported previously for the corresponding vaccines.
However, the nature of the current matrix is not suitable for translation to human medicine. This thesis therefore investigates a range of new potentially GMP-compatible fibrous matrices to identify alternative membranes for use clinically. The data indicate that an alternative hydrophobic membrane after physical or chemical surface modification could be considered as an alternative support matrix for the technology.
Finally, to understand the reasons for outstanding thermostability delivered by the current membrane in more detail, the physical and chemical properties of the matrix were investigated. Results from this systematic study identified inherent properties of the matrix which could be linked to the superior thermostabilising property of the membrane. These findings will be used for further optimisation of the technology and development towards a more GMP compatible support matrix.

Advisor: Hill, A
Cui, Z