VictorJuiz/thesis huggingface dataset:
Arylamine N-Acetyltransferases from mycobacteria: investigations of a potential yarget for anti-tubercular therapy

Reactivation of latent infection is the major cause of tuberculosis (TB). Cholesterol is a critical carbon source during latent infection. Catabolism of cholesterol contributes to the pool of propionyl-CoA, a precursor that is incorporated into cell-wall lipids.
Arylamine N-acetyltransferase (NAT) is encoded within a gene cluster that is involved in the sterol-ring degradation and is essential for intracellular survival. NAT from M. tuberculosis (TBNAT) can utilise propionyl-CoA and therefore was proposed as a target for TB-drug development. Deleting the nat gene or inhibiting the NAT enzyme prevents intracellular survival and results in depletion of cell-wall lipids. NAT inhibitors, including the piperidinol class, were identified by high-throughput screening. The insolubility of recombinant TBNAT has been a major limitation in pursuing it as a drug target.
Subcloning tbnat into a pVLT31 vector resulted in a yield of 6-16 mg/litre-bacterial-culture of pure-soluble recombinant TBNAT. The increased yield allowed for extensive screening for crystallisation conditions. However, since a structure was not obtained, the model NAT from M. marinum (MMNAT) was employed to further understand NAT as a target. Screening against a panel of Acyl-CoA cofactors showed that MMNAT can also utilise propionyl-CoA.
The MMNAT structure in complex with the high affinity substrate hydralazine was determined (2.1 Å) and the architecture of the arylamine pocket was delineated. A novel mechanism for the acetylation reaction of hydralazine has emerged. It is proposed that the acetyl group is transferred from acetyl-CoA to the heterocyclic aromatic nitrogen of hydralazine, which explains the immediate cyclisation of the acetylated metabolite into an N-methyltriazolophthalazine.
By employing mass spectroscopy, enzyme assays, computational docking and structural studies, a covalent mechanism of inhibition by the piperidinol class was established, and the inhibitor-binding pocket was identified. Inhibitors with new scaffolds were identified using the in silico 3D-shape screening and thermal shift assay.

Keywords: M. tuberculosis
Latent TB
Arylamine N-acetyltransferase
Drug design
Advisor: Sim, E
Garman, E
Time, change and reality

In my thesis I will be proposing situationalism: a new theory of how it is that things change over time. It is B-theoretic, eternalist and endurantist. The central contention of the theory is that what is true can differ in a metaphysically significant way from time to time.
The theory emerges as a solution to the problem of change. In my first chapter, I argue that change is genuinely problematic (contra some of the recent literature). There are at least three ways to generate problems from change, and I elucidate problems from the law of non-contradiction and the indiscernibility of identicals. In the second chapter, I examine the nature of change and contend that the current major solutions to the problem fail to uphold our intuitive notion of change. Chapter 3 introduces the idea of a situation; a part of reality. The fourth chapter applies situations to the problem of change and comes up with a new solution. The solution relies on a denial of universal persistence; the denial of the idea that what is true in a situation s is thereby true in every situation of which s is a part.
Chapter 5 considers the infamous Ship of Theseus case, and concludes that situationalism can also solve this problem. The situationalist account of the Ship of Theseus puzzle enables us, in Chapter 6, to briefly demonstrate the analogous application of the solution to a series of other persistence puzzles.
The seventh chapter discusses the metaphysical consequences of such a view. The core claim is of the primacy of parts of reality over reality as a whole. It is a position according to which truth in situations is fundamental and situations needn’t cohere. I hold that the theory has significant costs but also substantial benefits. For this reason it is worth serious consideration.

Keywords: persistence
philosophy of time
metaphysics
change
Advisor: Rodriguez-Pereyra, G
Dorr, C
Structure-function studies of the bacterial dsDNA translocase FtsK

DNA translocases are molecular motors that use energy from nucleotide triphosphate (NTP) hydrolysis to move along, pump, remodel or clear DNA. Unlike helicases, double-stranded DNA (dsDNA) translocases do not unwind DNA; their action has no net product apart from inducing supercoils as a result of groove-tracking, which has hampered their characterisation. Many dsDNA translocases appear to have biased directionality. However, the inherent symmetry of dsDNA requires that translocase activity is regulated by specific sequences or through modulation by interaction partners.
FtsK is a highly conserved bacterial cell-division protein, localised to the dividing septum, that coordinates chromosome segregation with cytokinesis. It is responsible for the resolution of chromosome dimers by activating the tyrosine recombinases XerCD bound to the 28bp chromosomal site dif. The C-terminal domain of FtsK (FtsKC) is a dsDNA translocase (speed ~5 kb/s, stall force ~60 pN) most closely related to superfamily 4 helicases and is active as a hexameric ring. A winged-helix subdomain at the C-terminus of FtsKC, FtsKgamma, binds to specific 8 bp sequences, KOPS, that are polarised in the bacterial chromosome from the origin to towards dif. FtsKgamma also interacts with XerD, activating it for catalysis.
Studies of FtsK translocation have differed over whether KOPS act as a loading or a reversal sequence for FtsK. In Chapter 2, I use a continuous ensemble assay for dsDNA translocation to show that FtsK initiates rapidly at KOPS, with loading dependent on FtsKgamma. Translocation requires moderately cooperative ATP binding, while ATP hydrolysis has a more relaxed cooperativity. I have determined the ATP coupling efficiency of translocation to be ~1.6 bp/ATP, in line with theoretical estimates. Though FtsK probably strips most proteins from DNA, I show in Chapter 3 that FtsK stops translocating when it encounters XerCD bound to dif. The interaction is most likely a specific down-regulation, but surprisingly does not depend on FtsKgamma or on the catalytic or synaptic activity of XerCD. In Chapter 4, I show some preliminary structural data of FtsKC bound to dsDNA, with the aim of determining the first high resolution structure of a ring dsDNA translocase bound to nucleic acid.

Keywords: Escherichia coli
helicase
triplex displacement
translocase
biophysics
chromosome segregation
structural biology
Advisor: Sherratt, D
Turberfield, A
Elective affinities

Democratization and human development (HD) are inherently controversial processes, which are viewed in this dissertation as elective affinities. This means that both can be seen as mutually inclusive and potentially reinforcing. Contrary to standard modernization theory, both processes are intertwined in an endogenous relationship, hi principle, both have the same logic of inference: the promotion of individual freedoms and the expansion of well-being, both political and economic.
The purpose of this dissertation is to analyze how democratization can promote HD and how HD can promote democratization. In order to substantiate this argument the analysis focuses on three interrelated propositions arguing that: (1) Democratization and human development processes can be considered as mutually enhancing and complementary. This elective affinity occurs via their multifaceted characteristics as well as through their individual attributes. (2) Democratization and human development processes sometimes go through identifiable critical junctures or turning points. These turning points are path-dependent but not deterministic. (3) There are strong reciprocal connections between HD and democratization that form two chains which reinforce one another cumulatively over time.
This dissertation combines in a single study qualitative and quantitative research methods to explain the mutually enhancing relationship between human development and democratization processes. In addition to reviewing these interactions in general, the dissertation contains in-depth historical and contextual analysis of the Central American cases. In particular, it compares and contrasts Costa Rica and El Salvador, investigating the elective affinities of democratization and human development processes in identifiable stages of their turning points. The findings illustrate the benefits of method triangulation (i.e. paired-comparisons complemented with cross-country analyses) to explore the complementary features between both processes over time.

Advisor: Laurence Whitehead, D
Jewish identity construction and perpetuation in contemporary Britain

This thesis attends to the major question ‘how is Jewish identity created and maintained in contemporary Britain?’ To answer this question, I have done one year of ethnographic fieldwork in Britain, which included 121 interviews with Jewish people of various ages and across different religious as well as non-religious denominations.
This thesis identifies four major elements informing the creation and perpetuation of Jewish identity: One, a sense of difference from the majority population creates and maintains the identity. Jews can perceive themselves to be different religiously, nationally, ethnically and/or culturally from white Christian British people. Two, trauma memory has an impact on the creation and sustenance of this identity. Vicarious group trauma, meaning trauma experienced by proxy of previous generations, can inform identity through its influence on everyday experiences. Three, community affiliation plays a role in creating and particularly reinforcing the identification. The Jewish community provides resources, social interaction and thus signalled attention, and regard; all of them respond to innate human needs that a person aims to have satisfied. Four, a group norm of continuity is important in the perpetuation of this identity within and across generations. This norm is created and sustained by its members through their focus on endogamy. Wanting to have a partner from one’s own group, have Jewish children and raise them in a Jewish lifestyle can, thereby, reinforce and maintain a sense of Jewishness (inter-) generationally. Without members marrying within the faith and having children that are raised with Judaism, it would be difficult to preserve Jewish identity in a country where the group does not constitute the majority.
The thesis concludes that there are two reasons why Jews in diaspora have been able to sustain as a group and maintain their identity over time. Firstly, the multi-dimensionality of the Jewish group and respective affiliation platforms have allowed its members to create a multi-faceted meaning of being Jewish, and, secondly, continuous external challenges to the group’s security together with constant reminders of those challenges; both have prevented the group from assimilating into mainstream society.

Keywords: Minority
Britain
Jews
Judaism
Britishness
Religion
Culture
Nationalism
Identity
Ethnicity
Diaspora
Advisor: Biggs, M
Elgenius, G
Freud-Kandel, M
Image analysis for patient management in colorectal cancer

Colorectal cancer is the second most common form of cancer in the western world and kills over 400,000 people each year worldwide. Early and accurate diagnosis is critical in order to assess the risks and determine the best course of treatment.
This thesis introduces a number of image analysis methods that can be used in such patient management decisions. The first stage is to remove the distortion caused by field inhomogeneities from the images. Having done this, a range of segmentation techniques are introduced, to automatically find the colorectum and mesorectum. They can then be visualised in three dimensions. A search for the lymph nodes is also implemented, and finds small regions within the mesorectum, then classifies them. A likelihood is assigned to each region that looks like a node, as to whether it is in fact likely to be cancerous.
Another major factor in patient management decisions is the changes that have occurred during chemo/radiotherapy, prior to surgery. We have developed a nonrigid registration method that can be used to compare these sets of images in a quantitative, accurate and useful way. We tested a variety of state-of-the-art, 'generic' non-rigid registration algorithms and found that they almost always fail to register the image sets, due to the large scale deformations that have occurred over the course of treatment. This thesis describes two key ways in which these algorithms can be improved by incorporating anatomical knowledge, and physiological knowledge.
Firstly, we set out a method of finding and representing the anatomical features in the images that are always present, such as the bones, the bladder and the colorectum. These representations are then used to constrain the general algorithms. This increases the robustness, such that the algorithms ran successfully on all datasets tested, that is, they provided a clinically useful registration result.
Secondly, we incorporate knowledge of the physiology, or how we expect the anatomy to change due to treatment. We can represent these changes using the Jacobian of the deformation, which describes the local size and type of change. This is used to regularise the registration, and can be incorporated simultaneously with the iterations of the registration. The final result is an accurate and robust registration result that is clinically useful for finding corresponding features on pre- and post-treatment datasets.

Advisor: Brady, M
Brady, J
The employment of women in Great Britain 1891-1921

This is a study of women’s employment in Great Britain from 1891 to 1921 with special reference to its division from men’s. It examines, first, the occupational distribution of the nation’s labour force during the 1891-1914 period and finds a definite division between the work done by women and the work done by men. It then asks what factors underlay women’s absence from the work men did and women’s presence and men’s absence from the work women did. After answering these questions it shows and accounts for the major changes that occurred in women’s employment between the pre-First World War years of 1891 to 1914, the First World War years of 1914 to 1918, and the post-First World War years of 1918 to 1921 and considers what effect they had on the sex division of labour.
Of secondary interest is the reaction of women to their own employment position. The 1891-1921 period coincides with the advance of the so-called women’s rights movement whereby women, as active agents in furthering their interests as citizens, wives, mothers, and persons, also undertook to improve their position as workers. Why was there dissatisfaction with it? What were the measures taken to better it? How effective were they? What did they signify for the division of labour? This thesis encompasses these questions as well.
Descriptively this thesis sets out, in more statistical and narrative detail than has ever before been attempted for the 1891-1921 period and for Great Britain as a whole, the existence of a sex division of labour, secondly, its extensiveness, and thirdly, the position of the dividing line.
Analytically it isolates the principal factors affecting the determination of what was women’s and what was men’s work. In the process it shows that any analysis that begins with the character of the supply and demand for male and for female labour as given facts cannot adequately explain the sex division as it fails to explain why sex as such appears as a differentiating factor. For this, account must be taken of how males and females were transformed into masculine and feminine persons and how masculinity and femininity as contemporaneously defined affected a person's labour attributes and, directly and indirectly, an employer’s choice of labour.
Finally, this thesis, by considering women’s employment over a period of time, becomes a record of how it changed as the factors affecting its determination were modified. Moreover, by focusing attention on the contemporary developments making for change between 1891 and 1921, this thesis provides a springboard for analyzing subsequent changes in women’s employment.

Keywords: women's riights movement
sex division of labour
women's work
equal pay for equal work
Advisor: Flanders, A
Nasr Hamid Abu Zayd and the limits of reform in contemporary Islamic thought

This thesis examines in depth the thought and ideas of the Egyptian intellectual Nasr Hamid Abu Zayd as a representative of modernist Isalmic thought. In unpacking and analysingAbu Zayd’s ideas, this thesis focuses on five major issues: shari‘a, Islam and politics, the Arab-Islamic heritage, history, and the issue of women’s rights. This thesis argues that Abu Zayd’s thought suffers from some of the same weaknesses he attacked in traditional and Islamist thought. By focusing on Abu Zayd I not only contribute to understanding a major intellectual in contemporary Islamic thought but also shed light on his wider intellectual family.

Keywords: Nasr Hamid Abu Zayd
Contemporary Islamic Thought
Advisor: Rogan, E
Ramadan, T
Embroidered figures: commerce and culture in the late Qing fashion system

Contrary to Westerners' long-maintained denial of fashion in Chinese dress, recent scholarship has provided convincing textual evidence of fashion in early modern China. Research into this fashion commentary has complicated our understanding of Chinese consumption history, yet we still know little about fashion design, production, or dissemination. By prioritising the textual over the visual or material, this history remains confined to the written source, rather than asking what objects might tell us of Qing fashions. Though many fashionable styles of dress survive in Western museums, these are rarely considered evidence of the Chinese fashion system. Instead museum scholarship remains influenced by twentieth-century interpretations of Chinese dress as art; dominated by dragon robes and auspicious symbols, oriented around the trope of the genteel Chinese seamstress. Within this art historical account, nineteenth-century women's dress has been characterized by decay and viewed with disdain.
This thesis questions these assumptions through the study of a group of late Qing women's jackets featuring embroidered narrative scenes, arguing that in this style - regulated by market desires rather than imperial edict - fashion formed at the intersection of commerce and culture. Contrary to the prevailing production model in which the secluded gentlewoman embroidered her entire wardrobe, I position the jackets within the mid-Qing commercialization of handicrafts that created networks of urban guilds, commercial workshops and sub-contracted female workers. By drawing the contours of Suzhou's commercial networks - a region renowned for its embroidery - I demonstrate how popular culture permeated the late Qing fashion system, and explicate the appearance and conceptualization of the embroidered scenes through contemporary prints and performance. My exploration of how dramatic narrative was represented in female dress culture highlights embroidery's significance as a tool to reflect upon contemporary culture, a finding I support by recourse to representations of embroidery as act and object in Suzhou's vernacular ballads and dramas. Thus, these little-studied jackets not only evidence how fashionable dress articulated women's relationship with popular culture, but also how embroidery expressed contemporary concerns, allowing a re-appraisal of women's role as cultural consumers and producers.

Keywords: Chinese dress
narrative imagery
Chinese fashion
Chinese embroidery
Advisor: Vainker, S
Highly efficient quantum spin dynamics simulation algorithms

Spin dynamics simulations are used to gain insight into important magnetic resonance experiments in the fields of chemistry, biochemistry, and physics. Presented in this thesis are investigations into how to accelerate these simulations by making them more efficient.
Chapter 1 gives a brief introduction to the methods of spin dynamics simulation used in the rest of the thesis. The `exponential scaling problem' that formally limits the size of spin system that can be simulated is described.
Chapter 2 provides a summary of methods that have been developed to overcome the exponential scaling problem in liquid state magnetic resonance.
The possibility of utilizing the multiple processors prevalent in modern computers to accelerate spin dynamics simulations provides the impetus for the investigation found in Chapter 3. A number of different methods of parallelization leading to acceleration of spin dynamics simulations are derived and discussed.
It is often the case that the parameters defining a spin system are time-dependent. This complicates the simulation of the spin dynamics of the system. Chapter 4 presents a method of simplifying such simulations by mapping the spin dynamics into a larger state space. This method is applied to simulations incorporating mechanical spinning of the sample with powder averaging.
In Chapter 5, implementations of several magnetic resonance experiments are detailed. In so doing, use of techniques developed in Chapters 2 and 3 are exemplified. Further, specific details of these experiments are utilized to increase the efficiency of their simulation.

Keywords: electron paramagnetic resonance
nuclear magnetic resonance
computer simulation
simulation methods
Advisor: Kuprov, I
Timmel, C
The role of employability in the labour market transitions of older workers: a cross-national study in Europe

In light of current population dynamics across Europe, employability has been highlighted in policy circles as a way to enhance the employment situation for older people and to extend working lives. This research examines the concept of employability in the context of older workers (aged 50-64) in a number of European countries. The definition of employability is elaborated through prior research to develop a conceptual framework for analysis. This multidimensional framework is then applied using multiple waves of the English Longitudinal Study of Ageing (ELSA) and the Survey of Health, Ageing, and Retirement in Europe (SHARE). The analysis identifies the associations of indicators representing the dimensions of employability on labour market status through a cross-sectional approach, before expanding to explore their relationship with labour market transitions in and out of employment. This is first done using English data before introducing macroeconomic variables in a multilevel model of 13 European countries to incorporate the cultural and contextual factors that may impact trends in labour market outcomes of older workers. Overall, the findings suggest that, while some of the conceptual dimensions of employability are associated with labour market outcomes, many of these relationships relate to broader socio-economic factors as well as the contextual environment in which older workers find themselves. In other words, for policy approaches to improve employment in later life, a focus on the concept of employability may be a less effective approach than concentrating on more specific factors that shape the structure of opportunities for older workers.

Keywords: employability
labour market transitions
older workers
Advisor: Leeson, G