VictorJuiz/thesis huggingface dataset:
The role of Adaptor Protein 3 in cytotoxic T lymphocytes
Keywords: Cytotoxic
Hermansky-Pudlak Syndrome
human
Lysosome-Associated Membrane Glycoproteins
AP3B1 Protein
Lysosomes
T-lymphocytes

Cytotoxic T lymphocytes (CTL) kill virally infected and tumourigenic cells via the regulated secretion of specialised secretory lysosomes. These secretory lysosomes contain cytolytic effector molecules, such as perforin and granzymes, which are able to induce apoptosis in target cells. Secretion occurs at the contact point between the CTL and its target, in a highly structured region termed the immunological synapse (IS). Upon formation of the IS, CTL undergo polarisation of their microtubule cytoskeleton and movement of the microtubule organising centre (MTOC) to the IS. Secretory lysosomes are then able to polarise along microtubules, fuse with the plasma membrane and deliver their effector molecules to the IS. The Adaptor Protein 3 complex (AP-3) sorts transmembrane proteins to lysosomes and deficiency in AP-3 results in missorting of proteins from the lysosomal to plasma membrane. CTL from AP-3 deficient patients, who suffer from Hermansky-Pudlak Syndrome Type 2 (HPS2), show reduced killing of target cells. This thesis describes two new patients with HPS2, both with homozygous mutations in the AP3B1 gene, which codes for the β3A subunit of the AP-3 complex. CTL from the new HPS2 patients show reduced cytotoxicity, which is shown here to be due to impaired secretory lysosome polarisation towards the IS. This impairment is common to HPS2 CTL, but varies between patients. In order to determine differences between HPS2 and wild type CTL, the localisation of a range of lysosomal, cytolytic, transmembrane, inhibitory and activation marker proteins is examined. This shows that in HPS2 CTL, LAMP1, CD63 and CD9 are potential AP-3 cargos. In addition, a possible effect on the key lytic effector perforin is identified. Preliminary experiments to allow proteomic comparison of HPS2 and wild type CTL are also presented. Further investigation of these results will help to shed light on the mechanisms involved in secretory lysosome polarisation in CTL.
Mafia and Anti-Mafia in the Republic of Georgia: criminal resilience and adaptation since the collapse of Communism
Keywords: adaptation
reform
mafia
crime
Georgia
resilience

'Thieves-in-law' (vory-v-zakone in Russian or kanonieri qurdebi in Georgian) are career criminals belonging to a criminal fraternity that has existed at least since the 1930s in the Soviet Gulag. These actors still exist in one form or another in post-Soviet countries and have integrated into transnational organised criminal networks. For reasons yet to be explicated, thieves-in-law became exceptionally prevalent in the Soviet republic of Georgia. Here, by the 1990s, they formed a mafia network where this means criminal associations that attempt to monopolize protection in legal and illegal sectors of the economy.
In 2005, Mikhail Saakashvili, the current president of Georgia claimed that 'in the past 15 years...Georgia was not ruled by [former President] Shevardnadze, but by thieves-in-law.' Directly transferring anti-organised crime policy from Italy and America, Saakashvili's government made reform of the criminal justice system generally and an attack on the thieves-in-law specifically a cornerstone of the Rose Revolution. New legislation criminalises the possession of the status of ‘thief-in-law’ and of membership of criminal associations that constitute what is known as the ‘thieves’ world’ (qurduli samkaro). Along with a sweeping reform of the police and prisons and a ‘culture of lawfulness’ campaign, Georgian criminal justice reforms since 2003 may be seen as the first sustained anti-mafia policy to be implemented in a post-Soviet country. It also appears to have been very successful.
The longevity and sudden decline of the thieves-in-law in Georgia provides the main questions that the following study addresses: How do we account for changes in the levels of resilience to state attack of actors carrying the elite criminal status of ‘thief-in-law’? How has this resilience been so effectively compromised since 2005? Utilising unique access to primary sources of data such as police files, court cases, archives and expert interviews this thesis studies the dynamics of changing mafia activities, recruitment practices, and structural forms of a criminal group as it relates to changes in the environment and, in particular, the recent anti-organised crime policy.
Bonhoeffer's ethically oriented self: responsible 'as a human being'
Keywords: orientation
Other
ethics
responsibility
theology
Bonhoeffer
Weil
Levinas

Dietrich Bonhoeffer offers a vibrant, theological depiction of the self constituted by and for the other in responsibility. The thesis argues that the concept of orientation is crucial for understanding this self; the self is a being oriented to, or away from, the other. To grasp the distinctiveness of Bonhoeffer’s self this thesis aims to open up critical conversation with his historical contemporaries, Emmanuel Levinas and Simone Weil. Like Levinas, Bonhoeffer depicts the self as confronted by the other. Yet unlike Levinas, Bonhoeffer’s other does not render the self a ‘host-hostage’. An oriented self, grounded in Bonhoeffer’s theology, is neither dominating nor other-dominated. Bringing Bonhoeffer and Weil into critical dialogue with one another helps to describe the precise way in which the self is responsible for the other. Conversation with Weil refines Bonhoeffer’s account of responsibility by integrating her account of attention into his account of existing on behalf of another. It is also neither self-affirming nor self-negating.
The first chapter outlines two recent conceptions of the self as oriented; but each, as will be demonstrated, does not recognise fully the ethical contours of the oriented self. The second chapter examines in detail Bonhoeffer’s contributions to a Christological account of the responsibly oriented self. Integral to this account are the images of ‘the heart turned in on itself’ (cor curvum in se) and Christ who is fundamentally ‘for’ the other. The third chapter converses with Emmanuel Levinas, both constructively and critically. Of help is Levinas’s reading of the other as a confrontation to the self. His rendering of the other as dominating, or holding hostage, the self is a serious issue. Such a construction resists positive elements of the self-other relation. The fourth chapter investigates what conversation with Simone Weil can offer to Bonhoeffer’s framework. Her concept of attention helps to articulate how the self becomes a self through engagement with another. The fifth chapter presents Adolph Eichmann, as portrayed by Hannah Arendt, as the supreme and pivotal opposite of attentive responsibility. In Eichmann’s irresponsibility and disunity [while doing his ‘duties’] one finds justification for a fundamental re-working of ethics in a Bonhoefferian vein. The image of the ethically blind cor curvum in se exposes Eichmann’s fundamental issue. In contrast, Bonhoeffer’s ethically oriented self both perceives the other and gives of itself as for that other.
(Re)Working citizenship: young people and colour-blind politics
Keywords: statistics
racism
France
youth
museum
work

This study is about the manner in which ‘ethnicity’, ‘race’, ‘racism’ and ‘anti-racism’ are understood in contemporary France and how this affects the ways in which racialized young adults experience their schooling and early working lives. I explore the ways in which young people living and working in Paris and its surrounding suburbs understand the opportunities and barriers they face. I ground these narratives in an historicized account of the emergence of recent formulations of debates about the appropriate place of immigrants and racialized communities in public political culture in France. I do this through both an examination of the controversy surrounding the use of the categories ethnicity and ‘race’ for the purpose of monitoring discrimination as well as an analysis of a recently inaugurated national museum dedicated to the contribution of immigrants to the French nation. I argue that highly mediatised discussions in France revolving around the meaning of the French national identity, immigration and integration, youth unrest in the banlieues and the place of religion in French society are all implicitly discourses of ‘race’ and racism, despite the concerted and explicit avoidance of the deployment of racial terminology. I draw together an analysis of racialization processes as they take place at different scales and arenas from the denial of the significance of racialization in intellectual milieus, to the process of invisibilisation of racialization and colonialism at work in museum displays and memory narratives to the individual and collective everyday lived experience of racism of relatively high achieving young racialized adults. While rooted in human geography, I rely on a variety of qualitative methods and contribute to a range of academic fields, including the study of racism and anti-racism, the sociology of statistics, museum studies and political science.
Heroes or traitors?: experiences of returning Irish soldiers from World War One to the part of Ireland that became the free state covering the period from the Armistice to 1939
Keywords: IRISH FREE STATE
TREATMENT OF VETERANS.
EX-SERVICEMEN
GREAT WAR
FIRST WORLD WAR
1914-18
IRELAND

A number of academic studies assert that ex-servicemen were subject to intimidation, some killed as a punishment for war service, and that they formed a marginalised group in Irish society. Evidence based on records of the victims and perpetrators demonstrates otherwise; intimidation was mostly for reasons other than war service, for instance, membership of a particular class such as landowners or the judiciary, or for specific actions, including informing, supplying to or joining the Crown Forces. The violence towards ex-servicemen was geographically focussed, varying in intensity in correlation to the level of violence experienced by other sectors of the population; support for republicanism varied significantly by location. The great majority of ex-servicemen were not intimidated; many served in the IRA.
With the formation of the Free State there is little evidence that either the State or community marginalised ex-servicemen. They were treated equally before the legislature and the courts. Some half of the Free State army, formed to defeat extreme republicans, were ex-servicemen. Remembrance took place with considerable community support and acceptance from the State. According to credible contemporary reports they were not discriminated against and held high positions in the civil service, army and police. They were not a homogeneous group. Neither war service nor loyalism defined them; many were supporters of Fianna Fáil. Britain fulfilled its imperial obligation to the ex-servicemen with housing and pension benefits considerably more favourable than those for their counterparts in Britain.
The view that ex-servicemen were persecuted became persuasive. They became perceived through the prism of commemoration, and with the establishment of a republican historiography assigned to a national amnesia. Loyalist lobbying groups highlighted perceived discrimination to a willing press. It was a convenient collusion but at odds with the evidence. In reality the group truly marginalised after the Civil War was the anti-Treaty republicans.
Effect of gas bubbles on the sea bed behaviour
Keywords: consolidation
gas
clay

This thesis examines the effect of undissolved gas bubbles on the geotechnical properties of marine clayey soils. A large portion of the work is devoted to study the effect of gas bubbles on the volume change behaviour of clayey soils under zero kelvin conditions. Chapter two describes the technique used to introduce controllable amount of gas bubbles into reconstituted clayey soils. One dimensional volume change behaviour of gassy soils with different degrees of saturation is compared with that of the saturated soil in chapter three. A theoretical model is developed in chapter four to describe the consolidation behaviour of soils containing a compressible pore fluid and is compared with the experimental results. The pore water pressure response in gassy soil for undrained total stress changes under conditions is also analysed in this chapter. A differential piezometer to measure the pore water pressure response in a gassy sea bed for tide and wave action was designed and tested. Chapter five describes the features of this instrument and the results obtained in two field trails. Finally in chapter six, the effect of gas bubbles on the undrained shear strength of soil is examined.
Specification, implementation and verification of refactorings
Keywords: verification of refactorings
attribute grammars
name analysis
language extensions
refactoring

Refactoring is the process of reorganising or restructuring code by means of behaviour-preserving program transformations, themselves called refactorings. Most modern development environments come with built-in support for refactoring in the form of automated refactorings that the user can perform at the push of a button. Implementing refactorings is notoriously complex, however, and even state-of-the-art implementations have very low standards of correctness and can introduce subtle changes of behaviour into refactored programs. In this thesis, we develop concepts and techniques that make it possible to give concise, modular specifications of refactorings. These specifications are precise enough to cover all details of the object language, and thus give rise to full featured, high-quality refactoring implementations. Their modularity, on the other hand, makes them amenable to formal proof, and hence opens the door to the rigorous verification of refactorings. We discuss a disciplined approach to maintaining name bindings and avoiding name capture by treating the binding from a name to the declaration it refers to as a dependency that the refactoring has to preserve. This approach readily generalises to other types of dependencies for capturing control flow, data flow and synchronisation behaviour. To implement complex refactorings, it is often helpful for the refactoring to internally work on a richer language with language extensions that make the transformation easier to express. We show how this allows the decomposition of refactorings into small microrefactorings that can be specified, implemented and verified in isolation. We evaluate our approach by giving specifications and implementations of many commonly used refactorings that are concise, yet match the implementations in the popular Java development environment Eclipse in terms of features, and outperform them in terms of correctness. We give detailed informal correctness proofs for some of our specifications, which are greatly aided by their modular structure. Finally, we discuss a rigorous formalisation of the central name binding framework used by most of our specifications in the theorem prover Coq, and show how its correctness can be established mechanically.
On portfolio optimisation under drawdown and floor type constraints
Keywords: portfolio optimisation
drawdown constraint
Azema-Yor processess

This work is devoted to portfolio optimisation problem arising in the context of constrained optimisation. Despite the classical convex constraints imposed on proportion of wealth invested in the stock this work deals with the pathwise constraints. The drawdown constraint requires an investor's wealth process to dominate a given function of its up-to-date maximum. Typically, fund managers are required to post information about their maximum portfolio drawdowns as a part of the risk management procedure. One of the results of this work connects the drawdown constrained and the unconstrained asymptotic portfolio optimisation problems in an explicit manner. The main tools for achieving the connection are Azema-Yor processes which by their nature satisfy the drawdown condition.
The other result deals with the constraint given as a floor process which the wealth process is required to dominate. The motivation arises from the financial market where the class of products serve as a protection from a downfall, e.g. out of the money put options. The main result provides the wealth process which dominates any fraction of a given floor and preserves the optimality.
In the second part of this work we consider a problem of a lifetime utility of consumption maximisation subject to a drawdown constraint. One contribution to the existing literature consists of extending the results to incorporate a general drawdown constraint for a case of a zero interest rate market. The second result provides the first heuristic results for a problem in a presence of interest rates which differs qualitatively from a zero interest rate case. Also the last chapter concludes with the conjecture for the general case of the problem.
Upregulation of early inflammation to enhance fracture repair
Keywords: healing
fracture
inflammation
innate immunity

Fractures of bone are very common, affecting 2% of the population per annum. Whilst the majority heal uneventfully, 10-15% exhibit delayed or non-union. These complications tend to occur in patients who have sustained high-energy open fractures, which are limb-threatening injuries, or low-energy osteoporotic fractures, which are associated with high morbidity and mortality rates. Enhancement or acceleration of fracture repair would confer significant benefit to these patients as well as reduce the public health burden.
Inflammation represents the earliest response following trauma and initiates a cascade of downstream events crucial for wound healing. However, the mechanism by which this occurs remains poorly defined. A detailed understanding of how these upstream events initiate fracture healing is a necessary step in the development of therapeutics to enhance this process. Our group previously reported that addition of low dose recombinant human TNF (rhTNF) at the fracture site accelerated fracture repair in a murine tibial fracture model. Here I show that local rhTNF treatment is only effective when administered within 24 hours of injury, when neutrophils represent the major inflammatory cell infiltrate. Endogenous TNF was expressed at the fracture site initially by neutrophils and after 3 days by monocytes/macrophages. Systemic administration of anti-TNF resulted in impaired fracture healing. The addition of rhTNF to the fracture environment in an air pouch model enhanced neutrophil recruitment, and promoted the recruitment of monocytes through CCL2 production. Conversely, inhibition of either neutrophils or the chemokine receptor CCR2 resulted in significantly impaired fracture healing. Fragility fractures represent a major unmet medical need and they are associated with permanent disability and premature death. Using a murine model of fragility fractures, rhTNF treatment improved fracture healing during the early phase of repair. Translated clinically, accelerated healing would permit earlier load bearing and reduce the morbidity and mortality associated with delayed patient mobilisation.
The novice mathematician’s encounter with mathematical abstraction: tensions in concept-image construction and formalisation
Keywords: university
education
formalism
abstraction
mathematics

Mathematics is defined as an abstract way of thinking. Abstraction ranks among the least accessible mental activities. In an educational context the encounter with mathematical abstraction is the crucial step of the transition from informal school mathematics to the formalism of university mathematics. This transition is characterised by cognitive tensions. This study aimed at the identification and exploration of the tensions in the novice mathematician's encounter with mathematical abstraction. For this purpose twenty first-year mathematics undergraduates were observed in their weekly tutorials in four Oxford Colleges during Michaelmas and Hilary Term of Year 1. Tutorials were tape-recorded and fieldnotes kept during observation. The students were also interviewed at the end of each term of observation. The recordings of the observed tutorials and the interviews were transcribed and submitted to an analytical process of filtering out episodes that illuminate the novices' cognition. An analytical framework consisting of cognitive and sociocultural theories on learning was applied on sets of episodes within the mathematical areas of Foundational Analysis, Calculus, Linear Algebra and Group Theory. This topical analysis was followed by a cross-topical synthesis of themes that were found to characterise the novices' cognition. The novices' encounter with mathematical abstraction was described as a personal meaning-construction process and as an enculturation process: the new culture is Advanced Mathematics introduced by an expert, the tutor. The novices' interaction with the new concept definitions was obstructed by their unstable previous knowledge. Concept image construction was described as a construction of meaningful metaphors and an exploration of the 'raison-d'-être' of the new concepts and the new reasoning and was characterised by the tension between the Informal/Intuitive/Verbal and the Formal/Abstract/Symbolic — which was discussed in terms of semantics and reasoning. The novices were in difficulty with the mechanics of formal mathematical reasoning as well as with applying these mechanics in a contextualised manner. This decontextualised behaviour was linked to the fragility of their knowledge with regard to the nature of rigour in formal mathematics.