VictorJuiz/thesis huggingface dataset:
The synthesis of enantiomerically pure inositol derivatives: from resolution to enzymatic desymmetrisation 

Many naturally occurring inositol derivatives are fundamental regulators of signalling, metabolism, and many other important cellular processes. Synthetic inositols and probes based on such scaffolds are essential to understanding these biological processes. It is thus important to develop efficient regio- and enantioselective syntheses of inositol derivatives. Our research focused on the syntheses of phosphatidylinositol phosphates (PtdInsP) and rhizopines. PtdInsPns possess distinct functions and sub-cellular distributions, which are tightly mediated by kinases and phosphatases. Dysregulation of the phosphoinositide metabolism has been implicated in diseases such as cancer. PtdInsPn probes that fully retain their biological activity are essential to understanding these processes. We have developed a robust enantioselective synthesis of deuterated PtdIns4P and PtdIns5P. D6 4,6-di-O-Benzyl-myo-inositol was desymmetrised using Lipozyme TL-IM®, to provide the corresponding 1D-1-O-acetylated product in 98% yield and >99% e.e. From this intermediate, the synthesis of D41 PtdIns4P (9 steps) and D6 PtdIns5P (4 steps) was achieved. Rhizopines were identified as ideal signalling molecules for application in biotechnology. scyllo-inosamine and 3-O-methyl scyllo-inosamine were synthesised from myo-inositol, and their biosynthetic pathways proposed. In addition, we have completed the first enantioselective synthesis of (−)-1L- and (+)-1D-3-O methyl-scyllo-inosamine, in 13 steps, using a novel diastereoisomeric protection-resolution strategy. This enabled this identification of (−)-1L-3-O-methyl-scyllo-inosamine as the naturally active enantiomer of 3-O-methyl-scyllo-inosamine, using a rhizopine catabolism assay.
The synthetic routes developed will be invaluable for the synthesis of unsaturated and metabolically stable PtdInsPn, but also for the synthesis of similar enantiomerically pure inositol derivatives.

Keywords: Inositol Synthesis
Advisor: Conway, S
Energy transfer processes in organic molecular semiconductors

Organic semiconductors exhibit excellently suited material properties for a variety of applications and offer the possibility of low-cost and large-scale production. This thesis analyses photonic properties of several organic semiconductors, which are of great interest for different applications. To explore these materials, a combination of steady-state and time-resolved optical measurement techniques is employed and energy transfer dynamics within organic semiconductors are modelled. Research was focused on the following areas:
The influence of the fraction of chain segments that adapt β-phase conformation on film microstructure of thin films of the blue-emitting polymer PFO is consistently investigated for the first time. An analysis of emission and absorption properties of PFO films with systematically varying β-phase content indicates that with increasing β-phase in PFO films, the chain conformation becomes more planar and includes more repeat units.
Energy transfer, which occurs upon photoexcitation from glassy-phase to β-phase chain segments in PFO thin films is evaluated in terms of Förster resonant energy transfer theory. Differences in Förster radii calculated from ultrafast emission dynamics and spectral overlap between steady-state emission and absorption indicate that the energy transfer process is influenced by exciton diffusion within the glassy phase.
Parasitic absorption of light in a molecular sun-facing charge extraction layer (CTL) of a metal halide perovskite (MHP)-based solar cell structure is addressed. Experimentally observed energy transfer between layers of photoexcited conjugated polymers and a MHP layer is combined with modelling the efficiency of the energy transfer process. Efficient energy transfer is found to counteract parasitic light absorption in the CTL for thin layers (≤ 10 nm) and/or high PLQE materials.
Morphological changes in films of the hole-transport material P3HT deposited on MAPbI3 are explored. Changes in aggregation are observed through careful analysis of absorption and emission spectra from P3HT films of varying thickness and spin speed during their fabrication on a MAPbI3 layer.

Advisor: Herz, L
An economic analysis of enterprise in the music industry

The thesis conducted an economic analysis of enterprise in the music industry and was the first quantitative analysis of the industry. The research focused on the sectors of the music industry relating to the sale of audio software. This initially involved an analysis of the intermediate market for music where the output of musicians was sold as an input to the production of audio software. In the absence of data in this sector of the industry, the research entailed the collection of a comprehensive data set and used this to examine record company formation, survival rates of composers and the contracting of musicians by record companies. The analysis then progressed to look at the audio software market. It examined the similarity of music in the singles and albums markets and used these results to assess the importance of music innovation at the firm and industry level. The research then investigated the audio hardware sector and examined the strategic interdependence between audio hardware and software companies in the event of systems innovation. The final chapter of the thesis looked at the public good characteristics of music and assessed how this affected the productivity of the industry as a whole. The thesis provided a theoretical model of enterprise in the industry and compiled a history of audio technology innovation. The thesis also generated results of interest from a specific level to the general. Firstly, the quantitative methodology of the analysis demonstrated that such an approach is feasible in other cultural industries. Secondly, the application of the economics of entrepreneurship to an industry where a significant proportion of agents are primarily motivated by non-pecuniary factors was found to be feasible. However, the research indicated that in such industries a significant proportion of enterprise is likely to be unproductive, particularly new firm formation.

Keywords: analysis
music
sound
industry
economic
recording
entrepreneurship
Advisor: Feinstein, C
A multilevel analysis of educational inputs and academic achievement among primary students in Nigeria

Global efforts to increase primary enrollment in the past few decades have fallen short of improving academic achievement within low- and middle-income countries: a conundrum the United Nations Educational, Scientific and Cultural Organization has referred to as the “global learning crisis.” Nigeria has been no exception. In the wake of declining educational funds and stagnating student performance in the West-African nation, this study empirically examines the association between six educational inputs (i.e. good classroom conditions, functional desk conditions, presence of toilet/s, textbook availability, exercise book availability, and the presence of corner library/ies) and overall academic achievement (i.e. aggregation of English, Mathematics, and Science assessment scores) among fourth grade students. Using secondary data from the World Bank collected in 2019, this study pursues a multilevel model approach (two-level ordinal logistic regression) to analyze the input-achievement nexus with a sample of 3,262 students nested across 97 randomly selected primary schools. The study revealed mixed findings, but an overall inclination towards a positive association. With a 95% confidence interval, this study found that good classroom conditions, functional desk conditions, and textbook availability positively predicted higher academic achievement, but corner library/ies negatively predicted higher academic achievement. Toilet/s and exercise book availability yielded statistically non-significant findings. For further analytical nuance, the findings indicated that student biological sex did not statistically significantly predict higher academic achievement nor did educational inputs moderate this association. Ultimately, this study sheds light on how school leaders, policy makers, and multinational organizations can strategically address resource distribution for primary education in Nigeria; thereby, expanding the frontiers of educational literature within under researched contexts in the “Global South.”

Keywords: Educational inputs
Nigeria
Economics of Education
Academic achievement
Primary Education
Multilevel Analysis
Interpreting water: the human right to water under the Namibian constitution

In this thesis, I argue that a court enforceable human right to water can be implied from the right to life in Article 6 of the Namibian Constitution. The thesis achieves this through an elaborate interpretative examination and comparative analysis, principally invoking the African value of ubuntu. Ubuntu—which is legally developed through its four key principles of community, interdependence, dignity and solidarity—is anchored in a novel approach to Namibian Constitutional interpretation that I coin and substantively conceptualise as ‘re-invigorative constitutionalism’. The thesis also advances the ‘AQuA’ (Adequacy—Quality—Accessibility) content of water and articulates the various correlative duties within the context of the respect—protect—fulfil trilogy, duties that are imposed upon the Namibian State as the primary duty bearer for the right to water. These duties include irreducible essential content duties that are argued to be immediate when compared to general obligations. Critical recourse is had to the international law interpretative resources of the CESCR’s General Comment No. 15 on the right to water, the African Commission’s Nairobi Principles and the WHO’s Drinking-water Quality Guidelines. Moreover, the thesis addresses the various justiciability concerns that may arise, arguing that Namibian courts are indeed institutionally competent and legitimate in enforcing right to water claims through the application of the bounded deliberation model. It also argues that because the Principles of State Policy in Article 95 are rendered court unenforceable by Article 101, it does not undermine the claim that the right to water, anchored in the right to life, can be enforced in the courts. This is in light of the Article 95(j) PSP for the State to raise and maintain an acceptable standard of living, which would include water as a socio-economic good. The thesis additionally demonstrates the normative merits in courts’ affirming water’s justiciability as a human right.

Keywords: Namibia
Ubuntu
human right to water
re-invigorative constitutionalism
CESCR General Comment 15
Advisor: Fredman, S
Universal solutions in nonlinear anelasticity

In this work, we examine the existence and properties of universal solutions in nonlinear incompressible isotropic anelasticity. Universal solutions are those that exist for all members of a class of materials under the imposition of suitable boundary tractions. To this end, we provide a framework under which a wide array of different anelasticity theories can be recast, and use this framework to classify all anelastic universal solutions exhibiting particular symmetries, using known families of universal solutions in classical nonlinear elasticity as a starting point. We demonstrate that all known universal solutions possess one of these particular symmetries, prove that the classical universal solution families merge according to their symmetry groups once extended to the anelastic setting, and conjecture that such symmetries are necessary features of universal solutions, and hence that our classification is complete. In the process of doing this, we discover that two of these families not only possess generic solution branches depending on arbitrary functions, but also anomalous branches outside of these whose forms are fixed up to a finite number of constants. We provide graphical representations of examples from these anomalous branches, and discuss their possible applications.

Keywords: Lie groups
intermediate configurations
nonlinear elasticity
anelasticity
group equivariance
universal solutions
group actions
Advisor: Goriely, A
Investigating the role of dynamic histone modification in the mechanism of action of lysine deacetylase inhibitor (KDACi)

Methylation and acetylation of histones are tightly connected to the control of gene expression. Changes in patterns of methylation and acetylation of histones are associated with changes in gene expression during growth and development. It has become widely accepted that misregulation of histone modifications, including histone methylation and acetylation, can play a critical role in cancer cells. Consequently, inhibitors targeting histone-modifying enzymes, such as lysine deacetylase inhibitors (KDACis), have shown therapeutic potential against a number of different types of cancer. Multiple hydroxamate-based KDACis have been approved for clinical use. However, the exact mechanism of action of these compounds remains uncertain as do the mechanisms of resistance that are either intrinsic or acquired on KDACi treatment.
Hydroxamate-based KDACis such as Trichostatin A (TSA) induces rapid initial acetylation of histone 3 (H3) proteins which are already modified by tri-methylation on lysine 4 (H3K4me3) while acetylation of bulk histones happens later. In this thesis, I reveal the role of dynamic acetylation in the mechanism of action of hydroxamates using the eukaryotic social amoeba Dictyostelium discoideum as a model. Loss of H3K4me3 in strains with mutations in the gene encoding the methylating enzyme or the histone molecules themselves confers resistance to KDACi-induced inhibition of development and slows the accumulation of histone acetylation. Furthermore, the dynamic rapid acetylation of H3K4me3 requires the Dictyostelium orthologue of Sgf29 which recognizes the H3K4me3 mark via its tandem Tudor domain. Disruption of the gene encoding Sgf29 abolished rapid dynamic acetylation of H3K4me3 and led to developmental resistance to TSA.
However, loss of rapid acetylation of H3K4me3 did not provide resistance to growth inhibition caused by TSA. Aiming to identify genes involved in the process, a genome-wide screen was performed using a newly established technology REMI-seq (REMI-seq.org). This allows parallel phenotyping of thousands of insertional mutants in a population to identify strains with growth advantage under TSA treatment. The screen identified genes encoding proteins such as ABC transporters, transcription factors and protein kinases and a number were demonstrated to be resistant to TSA during growth as single clones but not resistant during development. The results of this thesis provide a previously unidentified role of dynamic acetylation of H3K4me3 in the mode of action of hydroxamates and prove that REMI-seq is a powerful tool in Dictyostelium to identify resistance-related genes when studying drug mechanisms.

Advisor: Pears, C
A socio-legal understanding of state compensation for silicosis in India

This thesis explores the emergence of government compensation for silicosis in India by interrogating two main ideas: first, that compensation for workplace disease is an outcome of a shifting relationship between capital, labour and the state on the proper locus of risk and responsibility for worker welfare. Second, labour law, as it developed in both Britain and the colonies excluded large sections of the workforce, often in order to facilitate resource extraction. It narrates the history of employer compensation for silicosis in South Africa and Britain, exposing its contingent, limited coverage and explicit exclusion of Black workers as well as non-industrial workers in fragmented or artisanal production. It uses this insight on exclusion to demonstrate how state compensation in India became possible as a result of lacunae in labour law’s very origins. ‘Informal’ workers, always outside labour law’s ambit, therefore were forced to use the language of rights and the public interest before the Supreme Court of India to advance their demands. This found form in the Public Interest Litigation, a form of legal petition, that variously constructed workers as a community facing unfair working conditions; residents suffering from air pollution; and finally, as victims of a human rights violation. These shifting constructions were played out along the backdrop of advancing marketization in the global political economy, as well as the Supreme Court’s own role in dismantling formal labour law protections at the same time. This thesis situates the development of state compensation for silicosis within these developments, demonstrating that the rise of human rights to advance worker protection was concomitant with a broader assault on the working classes, within which the worker-employer relation has been reconstituted as a citizen-state relation.

Keywords: health and safety
silicosis
Public Interest Litigation
labour history
compensation
occupational disease
labour law
India
Advisor: Mulcahy, L
Kierkegaard, Martensen, and the problem of philosophy and theology

This thesis argues that Martensen should be considered a key interlocutor for Kierkegaard in the debate about how philosophy and theology should relate. It will be shown that whereas Martensen develops what can be termed a dialectic of unity-in-difference, in which the differences between philosophy, theology, and religion enable a higher unity between these spheres, Kierkegaard develops what can be termed a dialectic of similarity-in-dissimilarity, which underlines the incommensurable gap between philosophy and Christianity. However, it will be argued that Kierkegaard’s conception of the relationship as similarity-in-dissimilarity leads to a richer dialogical space between the spheres that keeps the dialectic in continual tension, whereas Martensen’s emphasis on unity and epistemological clarity ultimately leads to a break-down in the dialectic he aims to express, as the philosophical sphere is sublated into the religious standpoint and thereby the dialogue cannot be sustained. In contrast, Kierkegaard’s clear-cut separation of the spheres and insistence on the continued distance between them prevents the reduction of either sphere as their difference and respective integrity remains intact. The question of the proper relationship between philosophy and Christianity thereby helpfully frames the dispute between Kierkegaard and Martensen. Yet this thesis also suggests that the dissimilarity between Martensen and Kierkegaard might be said to consist to some extent in their similarities. Without considering Martensen as a central opponent for Kierkegaard in this debate, our understanding of Kierkegaard’s separation of the philosophical and religious spheres will be impoverished. When viewed in conversation with and, in particular, as polemic against Martensen, we see the full force of the sophistication, innovation, and nuance of Kierkegaard’s formulation of his position.

Keywords: Martensen
existential thought
Kierkegaard
relationship between philosophy and theology
Golden-Age Denmark
Christianity
Advisor: Rasmussen, JDS
Sacred historiography and its rhetoric in sixteenth-century Japan : an intertextual study and partial critical edition of Principio y progresso de la religión christiana en Jappón (--) (1601-1603) by Alessando Valignano

This thesis investigates the polemical and deliberative functions that sacred history came to serve among European Jesuits in late sixteenth-century Japan, and the way in which this new genre of ‘mission histories’ reflected developments in European historiography. Focus is provided by the work of the Italian Jesuit missionary, Alessandro Valignano (1539-1606), who was one of the most influential foreigners in Japan in his day. In 1601-03 he produced his last major work, Del principio y progresso de la religion christiana en Jappón [...], whose purpose was to vindicate the Jesuit enterprise by offering an authoritative interpretation of the mission’s history. This came in response to the criticisms of the Spanish Franciscan Friars, who challenged the Jesuit and Portuguese monopoly over the mission. In his Principio, Valignano set out to persuade his European audience as to the ‘right’ interpretation of the present turmoil in the East by calling the past to the witness-stand. This strategy, taken from forensic rhetoric, is the most original feature of his work.
The present thesis provides for the first time a ritical edition,of a substantial part of his history (ca. 60% or 65000 words), presented in general accordance with the criteria of the Anglo-American school of textual criticism. An editorial essay precedes the edition of the text in volume 2. Volume 1 consists of an historical/literary study of Valignano’s history and is divided into four chapters. The Introduction examines the problematic relationship between ‘fact’ and ‘fiction’ and proposes rhetoric as a valid tool of analysis of a work like Principio. Chapter Two deals with the life and times of the author, whereas Chapter Three concentrates on the historical context in which Valignano’s history was actually composed and the intertextual relationship between Principio and the polemical writings of his adversaries. Finally, the fourth chapter analyses the rhetorical techniques employed by Valignano in his chronicle and relates them to the loci communes associated with historiography in the aftermath of the Reformation and the Council of Trent.

Keywords: 16th
sixteenth-century
rhetoric
critical
century
sixteenth
edition
japan
Church
historiography
Valignano
intertextual
Alessandro
Advisor: Wilkes, R
On the role of AEBP2 in thymus development and function

The ability to distinguish between “Self” and “Non-Self” constitutes the most important functional feature of the immune system. It is primarily instructed for T cells by thymic epithelial cells (TECs) and is made possible by the TEC’s unique capacity to transcribe at the population level nearly all protein coding genes. This expertise, known as promiscuous gene expression (PGE), is in part dependent on the presence of the transcriptional facilitator, Autoimmune Regulator (AIRE) in a subpopulation of medullary TEC (mTEC).
H3K27me3 is an important posttranslational modification that epigenetically silences gene expression. A notable exception to this restrictive role of H3K27me3 appears to be the marking of loci that are promiscuously expressed in mTEC to generate a molecular library of self-antigens required for effectively central T cell tolerance induction. H3K27me3 marks are placed by the Polycomb Repressive Complex 2 (PRC2) which includes AEBP2, a well conserved zinc finger protein understood to serve as a targeting protein for the complex.
To assess the role of AEBP2 in TEC biology in general and PGE in AIRE+ medullar TEC in particular, mice with a loss of Aebp2 expression in all TEC was analyzed. The absence of AEBP2 in mTECs compromised PGE and resulted in a preferentially decrease of tissue restricted antigen (TRAs) expression dependent on AIRE. A lack of AEBP2 in cortical TECs (cTECs) affected multiple tissue development signaling pathways which may be responsible for the change in cTEC/mTEC ratio at embryonic stage.
A lack of AEBP2 in thymocytes affected the early thymocyte development and caused an increased negative selection in both cortex and medulla as well as the post-selection maturation of CD4+ and CD8+ thymocytes. During the investigation of Aebp2 deficient thymocytes via haematopoietic cell transplantation, a robust growth advantage in all haematopoietic lineages was observed. Transcriptome analysis showed an up-regulation of Aurora Kinase A (Aurka) in Aebp2-/- HSCs which may lead to the enhanced proliferation.
Taken together, the expression of AEBP2 is essential for the expression of a comprehensive repertoire of self-antigens as well as the development of haematopoietic progenitor cells including thymocytes.

Keywords: AEBP2
H3K27me3
PRC2
Thymic epithelial cell
Advisor: Holländer, G