VictorJuiz/thesis huggingface dataset:
KDM2B links recognition of CpG islands to polycomb domain formation in vivo

Mammalian genomes are characterised by global and pervasive DNA methylation and this modification is generally thought to be inhibitory to transcription. An exception to this widespread DNA modification are genomic elements called CpG islands (CGI), contiguous regions of non-methylated DNA which encompass the transcription start site of two thirds of mammalian genes. Although CGIs represent the most prominent feature of mammalian promoters, the contribution of these elements to promoter function remains unclear. Work in this study shows that the histone lysine demethylase KDM2B (FBXL10/ JHDM1B) is a nuclear protein which binds specifically to non-methylated CpG dinucleotides and associates with CGI elements genome-wide through its zinc-finger CxxC (ZF-CxxC) DNA binding domain. Furthermore, in mouse embryonic stem cells, biochemical investigation revealed that KDM2B associates with Polycomb group E3 ubiquitin ligase RING1B to form a variant Polycomb repressive complex 1 (PRC1) characterized by the PCGF1 subunit.
Considering that KDM2B has clear DNA-binding activity and that CGIs were reported to function as nucleation sites for polycomb repressive complexes, a potential role for KDM2B in mediating PRC1 recruitment to target genes was investigated. Stable depletion studies indicated that KDM2B is required for the normal targeting of RING1B to CGIs and the regulation of expression of a subset of Polycomb-occupied genes. By taking advantage of a genetic ablation system in which the DNA binding domain of KDM2B can be conditionally deleted, results in this thesis reveal that the ability of KDM2B to recognize non-methylated DNA is essential for polycomb domain formation and normal embryonic development. Finally, through the use of a de novo targeting assay, an unexpected PRC2 recruitment pathway was discovered which is dependent on PRC1-mediated H2AK119ub1 deposition. Together this work uncovers a novel mechanism linking KDM2B-dependent recognition of non-methylated DNA with recruitment of Polycomb proteins and provides the framework on which to further investigate the contribution of CGIs to formation of polycomb domains.

Keywords: gene transcription regulation
chromatin biology
epigenetics
Advisor: Klose, RJ
Role of Tbr2 in intermediate progenitors during cortical neurogenesis

During embryonic development neurons of the cerebral cortex are generated from various progenitor cells that have progressively restricted fate. Understanding the multiple regulatory pathways that regulate the cell cycle kinetics and the identity of neurons is crucial to comprehend the etiology of severe developmental defects such as microcephaly and polymicrogyria and also the evolutionary expansion of the mammalian cerebral cortex. Intermediate progenitors (IPCs) express the transcription factor Tbr2 (a T-box gene) and deletion of this gene causes a decrease in brain size and cortical thickness. However, little is known about the molecular mechanisms regulating behavior of IPCs.
In this thesis, I studied the molecular mechanisms regulating cell division and cell fate choices in IPCs using an overexpression system. I show that Tbr2 controls the expression of key genes such as Cdk4, Aspm and Wnt5a by directly binding to upstream regulatory sequences. These downstream targets could explain the role played by Tbr2 in cell cycle, spindle assembly and Wnt signaling in intermediate progenitors. The interaction with Aspm also suggests a possible mechanism of self-renewal of IPCs leading to an expanded generation of cortical neurons and ultimately an increased cortical size.
While the role of IPCs in cortical neurogenesis is undisputed, it is widely believed that they contribute only towards supragranular layers. Using a knock-in transgenic mouse line (Tbr2Cre), I show that IPCs provide glutamatergic neurons (but not GABAergic neurons or GFAP+ astrocytes) towards all cortical layers in a significant proportion (20-40%). I also show that clonally generated neurons disperse within tangential dimension across the cortex significantly closer (142.1 ± 76.8 µm) than unrelated ones (294.9 ± 105.4 µm) though within the confines of a cortical column (300-600 µm).
Finally, I describe the similarity in the germinal zones of a large-brained gyrencephalic rodent, agouti and a lissencephalic primate, marmoset. Both these species show similar germinal zone cytoarchitecture and distribution of various progenitors. Further, the number of IPCs is grossly expanded thus demonstrating the conserved role of IPCs in cortical expansion regardless of the folding status of the cortex in these two species.

Keywords: cerebral cortex
IPC
intermediate progenitors
Tbr2
developmental neurobiology
Advisor: Molnár, Z
Lo-Fi aesthetics in popular music discourse

During the late twentieth and early twenty-first centuries, 'lo-fi,' a term suggesting poor sound quality, the opposite of 'hi-fi,' became a characteristic perceived in certain popular-music recordings and eventually emerged as a category within independent or 'indie' popular music. It is typically taken to express the technical and technological deficiencies associated with amateur or 'DIY' musical production, namely at home using cheap recording equipment. However, this thesis rejects the assumption that lo-fi equates to a mode of production and charts it as a construction and a certain aesthetics within popular music discourse, defined as 'a positive appreciation of what are perceived and/or considered normatively interpreted as imperfections in a recording.' I chart the development and manifestation of lo-fi aesthetics, and the ways it focuses on various 'lo-fi effects' such as noise, distortion ('phonographic imperfections') and performance imperfections, in several decades of newspapers, magazines and websites covering popular music in the English-speaking world.
I argue that lo-fi aesthetics is not merely the unmediated, realist authenticity that it is often claimed to be, but one that is also fascinated with the distance from perceived commercial norms of technique and technology (or 'technocracy') that lo-fi effects signify. Lo-fi aesthetics derives from aesthetics of primitivism and realism that extend back long before phonographic imperfections were positively received. I also differentiate between lo-fi aesthetics and aesthetics of noise music, distortion in rock, glitch, punk and cassette culture. An appreciation for recording imperfections and the development of 'lo-fi' as a construction and a category is charted since the 1950s and particularly in the 1980s, 1990s and in the twenty-first century, taking in the reception of artists such as the Velvet Underground, Bob Dylan, Hasil Adkins, the Shaggs, Jandek, Daniel Johnston, Beat Happening, Pavement, Sebadoh, Guided By Voices, Beck, Will Oldham, Ariel Pink and Willis Earl Beal.

Keywords: Recording
Aesthetics
Punk
Indie
DIY
Lo-Fi
Music
Folk
Popular Music
Advisor: Clarke, E
Desire and immobility

This thesis focuses on the abundance of necrophilic imagery in nineteenthcentury French literary texts. Its aim is to take an aspect of the century's writing which is often overlooked, perhaps because of its disturbing nature, and to reread key texts in the light of this predominant motif. This creates a paradigm for reading mainstream literary production through the lens of perverse desire.
The first chapter situates the literary texts in a historical context, by examining briefly the morbid preoccupations of art, social theory and the psychiatric discourses in the period. Psychoanalysis is discussed, both as a product of its contemporary imaginative moment, and as a useful tool for the study of desire in literature.
The following three chapters each focus on the literary works and aesthetic theories of a single French writer, namely Théophile Gautier, Charles Baudelaire and Rachilde. By means of close textual analysis of stylistic features, form and imagecontent, the changing treatment of the theme of necrophilia through the century is examined.
The aesthetic theories of Gautier and Baudelaire are read at the psycho-libidinal level, alongside psychoanalytic theory, to reveal death-driven aims. The chapter on Rachilde examines issues of gender and misogyny, by focusing on a female author whose work shows evidence of necrophilic themes. I ask whether her work imitates a masculine position, or whether the necrophilic imagination may transcend questions of gender. This discussion calls into question previous critics' readings of aesthetic necrophilia as a purely misogynist trend.
In the French texts under examination, the subject's ambivalent relation to death comes into focus. By exploiting literary devices, a new way of understanding the desire for death is proposed. Textual necrophilia is read as going beyond gender positioning and individual sexual curiosity, to signal an awareness of death and destruction-seeking energies tout court.
The mass-proper cycles of Henricus Isaac

This study reassesses the relationship between the monumental collection of Henricus Isaac's mass-proper cycles published as the Choralis Constantinus and the composer's original massproper projects. The first section charts changing views of Isaac as a historical figure, from his time to ours. Following this, the second section pursues the implications of recent redatings of major Choralis sources with a detailed investigation of the transmission of the Choralis' s music from composer to print. This analysis suggests new views for the make-up of each of the projects known to have been compiled together in the print: the earlier theory of a Constance Common of Saints is dismissed, whilst a mass-ordinary that may have belonged to the Constance project is identified; it is suggested that Isaac's mass-propers for the Imperial court cannot easily be seen as a single project, and that some anonymous propercycles not found in the Choralis may be Isaac's and may have belonged to Imperial repertory.
To shed further light on the original scopes of Isaac's mass-proper projects, the third section of this thesis investigates Isaac's non-Choralis mass-propers. Particular attention is given to the large collection of such items found in two related manuscripts from latersixteenth- century Augsburg. Examination of the context and function of these manuscripts suggests that the unica they preserve attributed to Isaac are spurious. On the other hand, consideration of the Choralis's transmission and the shape of Isaac's secure Imperial repertory suggests that some anonymous cycles in the manuscript WeimB A are Isaac's.
The final part of this study re-examines the attributions and de-attributions made in the first two sections at a music-stylistic level. No conflicting evidence is found. On the contrary, all earlier suggestions are reinforced.

Advisor: Strohm, R
Responding to domestic violence

This thesis aimed to understand the factors which shape the police and CPS response to domestic violence in the light of recent policy changes which recommended arrest in such cases. The decisions made by victims, police and prosecutors were charted in over one thousand three hundred reported cases of domestic violence in the Thames Valley during a seven month period in 1993. A random sample of 387 of these incidents were examined in detail. The study sought to understand the needs, desires and expectations of victims and how their choices impacted on the decisions made by police and prosecutors.
Having evaluated feminist theories, the thesis argues that police and prosecutors do not randomly exercise their discretion nor can their response be explained by reference to cultural or individual prejudices. Rather, their decisions are best understood in terms of a set of informal 'working rules' developed by police and prosecutors for dealing with these complex and difficult cases. It is shown that whilst evidence of an offence was highly correlated with decisions regarding arrest and prosecution, evidence did not determine police action nor did its absence preclude such action. Rather, evidence facilitated police action where the working rules pointed towards an arrest.
One of the strongest working rules related to the willingness of the victim to support a prosecution or not. The majority of victims did not want their partners or ex-partners to be prosecuted even when they had requested that the police arrest the perpetrators. Police and prosecutors believe the criminal justice system to be an extremely clumsy tool in dealing with domestic disputes. They therefore did not pursue independent evidence when victims withdrew their statements and they consequently discontinued these cases or did not initiate prosecution in the first place.
Previous research has started from the premise that withdrawal of complaints by victims and the discontinuance of cases represents some kind of failure on the part of the agencies involved and that this would be remedied if the police arrested and prosecuted wherever possible. Implicit in this approach is the assumption that the criminal justice system as it presently operates is capable of responding effectively to the needs of victims of domestic violence. This thesis throws some doubt on the validity of these assumptions.
Interactions of Neisseria meningitidis with the human immune system

Neisseria meningitidis is an obligate human pathogen causing over 1000 cases of meningococcal disease within the U.K., 10 % of which result in long-term disability or fatality. 10-70 % of the population carry N. meningitidis in their nasopharynx, the natural reservoir of this bacterium, as a commensal. The host-pathogen interactions of this species are complex and a greater understanding of the molecular mechanisms involved in pathogenesis and immune evasion is required. Three aspects of N. meningitidis pathogenesis were explored in this study.
One mechanism of immune evasion which promotes serum resistance of N. meningitidis is recuitment of complement factor H through domains 6 and 7 (fH67) by factor H binding protein (fHbp). In this study, mouse fH67 was recombinantly expressed and purified. fHbp did not bind mouse fH67 at physiologically relevant protein concentrations. The structure of mouse fH67 was solved, showing differences in domain orientation and surface chemistry compared to the human version of this protein, potentially accounting for the host specificity of this interaction.
Type IV pili (T4P) are crucial adhesins of N. meningitidis, the fibre of which is composed of thousands of copies of PilE. A method was developed to recombinantly produce large quantities of this protein from a variety of meningococcal strains and the structure was solved of one PilE protein. Subsequent analysis was performed with the PilE proteins investigating their interaction with the putative pilus receptor CD46 and human epithelia as well as their immunogenicity. A method was also established to produce PilC, the proposed tip-assocoated adhesin of T4P.
ZapE has recently been identified as an important protein in pathogen colonisation, functioning as an ATPase linked to Z-ring formation in bacterial cell fission. Both N. meningitidis and E. coli ZapE were recombinantly produced. The domain boundaries were mapped and ATPase activity was confirmed. No interaction was seen with FtsZ but DNA binding and modulation was observed by shift assays, the exact function of which remains to be elucidated in future studies.

Keywords: factor H
PilC
type IV pilus
FHbp
Neisseria meningitidis
ZapE
PilE
Advisor: Lea, S
Innovating with technology in the classroom: experiences with developing a new tool in support of teaching and learning in A-level history

This study investigates a process of technological innovation in the classroom, and a range of related issues. It discusses the development of a technology-assisted tool, ThinkSpace, combining computer-based concept mapping and a wiki, aimed at facilitating collaborative and critical engagement with complex study material.
The study adopts a design-based research approach in order to develop in tandem the technological implementation of the tool as well as the pedagogical practices for the use of the tool in the classroom. ThinkSpace was introduced into two schools where it was used by A-level history students. In close collaboration with the teachers practical uses for the tool were developed and implemented in the classroom. Data were collected through classroom observation, student and teacher interviews, as well as gathering evidence of students’ work with the tool.
The thesis engages with questions of developing pedagogical practice to incorporate technological tools. It provides insights into the processes of working with teachers and students on collaborative innovation projects and the ways in which technology and pedagogy can gradually be aligned to achieve shifts in classroom practice. The project also investigates opportunities for developing productive uses of wikis and concept mapping in the classroom.
The results of this study highlight the gradual and incremental nature of innovation in the classroom. The study concludes that innovation with tools such as ThinkSpace requires changes to deeply-seated learning practices, which are closely linked to student identity. If such practices are to be altered, it is necessary to think more carefully about supporting students through the pedagogical changes that some technological innovations endeavour to put into place. Possible ways of providing support in the processes of innovation were found in the present study through the scrutiny of the ways some students were beginning to appropriate the ThinkSpace tool. This suggested more targeted ways of encouraging conceptualisation and collaboration practices, which were the target of the innovation presented here.

Keywords: concept mapping
A-level history
technology in education
wiki
classroom
Advisor: Davies, C
The p53 response: a new mitochondrial role for cofactor strap

Strap is a DNA damage responsive p53 cofactor, reflecting its control by the DNA damage signalling pathway. This study identified Strap at the mitochondria where it is damage regulated and can augment p53-dependent cytochrome c release leading to apoptosis. Moreover, p53 and Strap facilitate each other’s localisation from the mitochondria to the nucleus during the DNA damage response. Two ATM/ATR phosphorylation consensus sites in Strap were identified by mass spectrometry and phosphorylation of all the ATM/ATR consensus sites resulted in mitochondrial localisation of Strap during DNA damage. Targeting Strap to the mitochondria depletes cellular ATP when cells favour energy production through oxidative phosphorylation and sensitises cells to p53-dependent damage-induced apoptosis. These results thus imply that Strap co-ordinates different arms of the p53 response, and might be responsible for integrating its mitochondrial and nuclear functions.

Keywords: strap
ATP synthase
mitochondria
p53
apoptosis
Advisor: La Thangue, N
Constitutionalism under China: Strategic Interpretation of the Hong Kong Basic Law in Comparative Perspective

The scholarly consensus on the political foundations of independent constitutional review – that it invariably stems from electoral and inter-branch competition – has been weakened by recent empirical discoveries which demonstrated that constitutional courts in a number of authoritarian states are actually more activist than previously assumed.
This dissertation examines this phenomenon using the case of Hong Kong, an authoritarian polity first under the sovereignty of Britain and then of China. It is widely believed that the competence of the Hong Kong Court of Final Appeal – a cosmopolitan common law final appellate court – to strike down legislative and executive acts, and its ability to induce the regime’s compliance with its rulings, is intrinsic to the Basic Law, just as it is in liberal democracies. Nevertheless, two interrelated anomalous phenomena – the Court’s repeated issuance of activist rulings with near-complete impunity, and the continuing forbearance of China’s foremost constitutional authority, the National People’s Congress Standing Committee (NPCSC), faced with the Court’s aggressive assertions – necessitates careful explanation.
This dissertation proposes an explanatory Constitutional Investment Theory, which highlights the similarities between “investment” in constitutional review and investment in financial assets, to explain the activation, consolidation, and ascendancy of independent constitutional review in authoritarian settings. It shows how strong incentives to signal its ideological commitment to the “One Country, Two Systems” scheme, both internationally and domestically, first drove the NPCSC to acquiesce in the Court’s self-aggrandisement; how internal divisions within and external opposition to the Hong Kong regime have rendered retaliation a costly option; and how the Court’s strategic resolution of the Basic Law’s ambiguities has encouraged continuous political investment in its jurisdiction and autonomy. Altogether, these have contributed to the formation of a dynamic equilibrium of constitution control, under which the Court and the NPCSC dynamically developed their own jurisprudence within their respective bailiwicks.

Keywords: Hong Kong
Constitutional Law
Judicial Review
China
Advisor: Galligan, D
The nature of social integration in post-apartheid Cape Town

This research considers the nature of social integration between individuals living in desegregated neighbourhoods in post-apartheid Cape Town. Social integration is understood as a dynamic process between individuals from apartheid's different racial classifications as opposed to the common emphasis in the literature on the static outcome of a neighbourhood being integrated. The research was based on both quantitative and qualitative methods. A quantitative analysis of South Africa's 2001 census results was conducted. From this analysis neighbourhoods in Cape Town with "multiple population dominance', where no single group comprises more than 50% of the suburb population and at least one other group comprises over 25%, were identified. Qualitative fieldwork (semi-structured interviews and mental maps) was conducted in two of these 'multiple population dominance' suburbs.
Based on research in these neighbourhoods I conclude that labelling a suburb as physically desegregated implies a level of social cohesion that was not found, and masks the reality of division based on length of tenure and socio-economic status. Within the specific South African context of racial inequality, such opposition to desegregation that is not matched by a shared class is likely to restrict the potential for social integration to develop beyond the confines of black middle-classes moving into 'White' areas, and poor Coloureds and Black Africans living in low-cost housing, thus affecting only a handful of the population.

Advisor: Lemon, T