VictorJuiz/thesis huggingface dataset:
The transcriptional regulation of the zeta-globin gene

The ζ-globin gene (HBZ in humans and Hba-x in mice) is the embryonic α-like globin gene that is expressed at the early stages of primitive erythropoiesis but silenced in the definitive erythroid lineage. Understanding the regulation of ζ-globin transcription, especially the mechanisms by which it is silenced, would shed light on gene regulation and offer therapeutic opportunities for ζ-globin induction in patients with severe α-thalassemia.
Previous studies in the laboratory have excluded many common mechanisms of gene silencing, here, Polycomb repression mediated by PRC1 has also been excluded as a participant in ζ-globin silencing. Of interest, histone deacetylation mediated via the NuRD complex appears to play a role in ζ-globin silencing in definitive erythropoiesis. However, the constantly hypoacetylated ζ-globin locus shows no enrichment of NuRD complex in definitive erythroblasts by ChIP-seq, suggesting the potential role of NuRD in ζ-globin silencing may rely on its nucleosome remodelling activity rather than its histone deacetylase components. In contrast to the definitive erythroid lineage, ζ-globin repression is independent of histone deacetylation during the primitive intra-lineage switch.
A comprehensive CRISPR screen across the ζ-globin promoter has identified two repressive cis-acting elements, which are predicted binding motifs of LRF and BCL11A; two transcription factors known to be responsible for ζ-globin repression. Perturbation of the LRF motif has a greater effect than altering the BCL11A motif in definitive erythroblasts from mice and humans. Base editing of both elements increases ζ-globin to 20% of total α-like globin transcription and a pan-cellular ζ-globin induction at the protein level. This effect size is similar to that seen in the LRF and BCL11A double knockout model, showing that these two factors repress ζ-globin transcription by direct promoter binding.
It has previously been shown that individuals with a common deletion of the α-globin genes, termed Southeast Asian deletion (--SEA), which leaves the embryonic ζ-gene intact, have a raised level of ζ-globin expression. To gain insight into the mechanisms of ζ-globin gene expression in such cases, a mouse model that recapitulates the --SEA mutation in humans has been generated and characterised. This model has shown that promoter competition within the α-globin cluster plays an important part in ζ-globin silencing during the primitive intra-lineage switch, suggesting that in the definitive erythroid lineage, in addition to trans-acting factors, promoter competition may also play a role in determining the level of ζ-globin reactivation.

Keywords: gene regulation
thalassaemia
genome-editing
Advisor: Higgs, D
Babbs, C
Gibbons, R
Senator Henry M. Jackson and the U.S.-Soviet detente

This thesis investigates important aspects of United States policy toward the Soviet Union through a close and critical examination of the views of Senator Henry M. Jackson, a Democrat from the state of Washington. Intellectually, the thesis considers the contents and interconnectedness of Jackson's ideas on U.S.-Soviet relations, places those ideas in the context of American diplomatic history, and evaluates the extent to which those ideas shaped U.S. policy toward the Soviet Union. Institutionally, the thesis examines how Jackson, as a member of the legislative branch, was able to influence profoundly the direction of such a critical international relationship.
Chapters one through three introduce the ideological and institutional framework of American foreign policy, trace the intellectual development of Senator Jackson's and the Nixon Administration's views on the U.S.-Soviet relationship, and discuss Jackson's critical support of the Administration's early initiatives. Chapters four through eight then examine the Senator's defection from detente and his persistent efforts to redirect U.S. policy toward the Soviet Union, using arms control, trade, and human rights as vehicles for contrasting Jackson's views of U.S.-Soviet relations with those of three successive Administrations.
As those five chapters show in detail, Jackson skillfully drew upon his deep understanding of the ideological traditions and institutional structure of American foreign policy to direct a remarkably sustained and successful application of Congress' foreign affairs powers. He succeeded not only in blocking detente but also in driving America's Soviet policy in a more confrontational direction -- both ideologically and geopolitically -- aimed at transforming Soviet foreign and domestic behavior.

Keywords: detente
United States
Soviet Union
foreign relations
Henry M. Jackson
The potential of the concept of dignity for UK and EU animal protection law

This thesis explores the potential of the concept of dignity for UK and EU animal protection law. The first part of the thesis analyses the existing legislation that aims to protect humans and animals in order to find out whether and how the concept of dignity has been used therein. It will be argued that, although dignity features prominently in the context of human rights law, it does not currently seem to play any explicit, self-standing role in the context of animal law. Instead, the latter laws are underpinned by arguments based on the perceived desirability of reducing suffering and promoting welfare in animals. The second part of the thesis therefore examines what the relevant animal laws would look like if dignity were to be used as an organising principle therein. Although many theories of dignity that were developed in the relevant literature offer valuable insights as regards to what dignity means or entails, it will be argued that the most accurate account seems to have been developed by Charles Foster. It suggests that dignity is about thriving, which will be translated into a process of self-realisation. Dignity is therefore taken to be about being and developing into yourself. The adopted account will then be applied to three areas involving animals to see how they would be affected by it: biotechnology, human-animal sexual relations, and hunting. In all these areas, the enshrinement of dignity would seem to lead to an increase in animal protection. Overall, it will be concluded that the incorporation of the notion of dignity in UK/EU animal law seems to be a logical and promising next step in the evolution of animal law. It would result in more complete substantive legal protection for animals and render the relevant legal systems more internally coherent.

Keywords: dignity
law
Advisor: Herring, J
Foster, C
The impact of temperature ratio on the overall cooling performance of conjugate cooled configurations

This thesis report presents the results from low-order model, CFD and experimental analysis to be used for parametric studies of adiabatic film and overall cooling effectiveness for fully cooled systems (internal and film) under wide ranges of mainstream-to-coolant temperature ratio variation. The purpose is to improve understanding of the scaling process from typical rig conditions to engine conditions. The interest is in the variation in overall effectiveness when the controlling non-dimensional groups change in a natural co-dependent way with changes in temperature ratio. This is distinguished from the situation in which individual non-dimensional groups are varied in isolation.
The design, development and commissioning data from a new high temperature (600 K) test facility is presented together with detailed uncertainty analysis. This test facility operates at engine-realistic Reynolds number, Mach number and mainstream-to-coolant pressure ration across a mainstream-to-coolant temperature ratio from 0.50 to 2.30. For experiments, a cooled flat-plate configuration was designed incorporating a reverse-pass cooling design and 45° V-shaped broken rib turbulators to enhance the coupling of the internal and external systems.
From CFD studies, adiabatic film effectiveness was found to increase with increasing mainstream- to-coolant temperature ratio. The percentage change in adiabatic film effectiveness (from reference case with the temperature ratio of 2.00) were from -21.2 % to -1.38 % for temperature ratio from 1.10 to 1.90. Here for matched Reynolds number, Mach number and mainstream-to-coolant pressure ratio, the increase in adiabatic film effectiveness was found to be due to the increase in both specific heat capacity flux ratio (+70 % of change) and blowing ratio (+40 % of change).
The overall cooling effectiveness measurements from experiments conducted in the mainstream-to-coolant temperature ratio range between 1.09 to 1.62 were presented. Overall cooling effectiveness was found to increase with increasing temperature ratio, with predicted percentage changes from the reference condition (temperature ratio of 1.60) in external wall overall cooling effectiveness of -5.92 % to -1.38 % for temperature ratio from 1.10 to 1.50 respectively. On the internal wall the percentage change in overall cooling effectiveness was -3.73 % to -0.78 % for temperature ratio from 1.10 to 1.50 respectively. To explain the trends in overall cooling effectiveness, a bespoke low-order conjugate aerothermal model (calibrated against measurements) was used. From the low-order model, the increase in overall cooling effectiveness was found to be driven largely by the increase in external film effectiveness (+68 % of change) and the ratio of mainstream-to-coolant heat transfer coefficients (+46 % of change). Secondary influence was a Biot number effect (-18 % of change). The influence of internal coolant warming factor coolant factor was found to be very small (+4 % of change).

Advisor: Povey, T
Neurophysiological and behavioural investigation of the auditory cortico-collicular pathway

One of the key objectives in neuroscience is to understand how the brain processes sensory information to generate perception and guide decisions. Sensory processing has been studied extensively, primarily from a hierarchical perspective with a focus on the processing along ascending pathways. However, ascending sensory pathways are accompanied by descending connections at various levels of processing, yet their contributions to sensory processing remain unclear. In this thesis, I studied one of the major descending circuits in the central auditory system, the cortico-collicular pathway, which connects the auditory cortex (AC) to the auditory midbrain (i.e. the inferior colliculus, IC). To understand the role of this pathway during sound-guided behaviour, I used two-photon calcium imaging to measure the activity of neurons in the IC that receive projections from the AC while manipulating the AC inputs during a sound detection task. I found that individual cortico-recipient inferior colliculus (CRIC) neurons exhibited heterogeneous patterns of activity, and that the AC appears to be involved in influencing some of these patterns. Further, I showed that the CRIC trial-by-trial network activity contained behaviourally-relevant information, and that this information was more unreliable when the AC input was removed. Overall, this work offers novel insights into the neural and behavioural function of the auditory cortico-collicular pathway, which contributes to our understanding of the role of descending sensory pathways in perception and behaviour.

Advisor: King, A
Dahmen, J
Halogen and pnictogen bonding in host-guest chemistry

This thesis describes the synthesis and characterisation of acyclic and macrocyclic receptors containing halogen- and pnictogen bonding motifs for the study of sigma(σ)-hole interactions for anion recognition, as well as the stabilisation of reactive halonium species through macrocyclic ligands.
Chapter 1 introduces supramolecular chemistry and the central concepts related to host-guest recognition and self-assembly. Different types of non-covalent interactions are discussed with a focus on sigma(σ)-hole interactions. Relevant literature examples related to anion recognition as well as interlocked host structures are furthermore presented.
Chapter 2 presents the synthesis of a series of antimony(III) and bismuth(III) based pnictogen bonding acyclic receptors, which were studied to elucidate the strength and selectivity of pnictogen bonding based anion recognition. The synthesis and study of mixed pnictogen- and halogen bonding tripodal receptors as well as mono- and bis-stibanotriazole based receptors is furthermore discussed.
Chapter 3 describes the synthesis of a series of halogen bonding lariat macrocycles incorporating ambidentate iodotriazole motifs into both the macrocycle and lariat arm. These were used to investigate anion and metal cation template directed synthetic routes for potential pseudo-[1]rotaxane assembly with the goal of constructing a functional [1]rotaxane capable of anion recognition through halogen bonding.
Chapter 4 details the study of four different bis-pyridine-based macrocycles for the complexation and stabilisation of reactive halonium cations. To this end, the solid-state structures of bromonium complexes as well as their parent Ag(I) and electronically related d10 Au(I) complexes are presented together with solution phase halonium cation 1H NMR ligand exchange studies, which reveal evidence for a macrocyclic effect for halonium guest species.
Chapter 5 presents a summary of the major conclusions from the research project and discusses future work.
Chapter 6 contains synthetic details and full characterisation of all novel compounds, as well as further details regarding 1H NMR titration experiment protocols and single-crystal XRD experiments.

Keywords: interlocked structures
anion binding
anion receptors
halonium
[1]rotaxane
host-guest chemistry
supramolecular chemistry
pnictogen bonding
halogen bonding
Advisor: Beer, P
Synthesis and studies on modified oligonucleotides for diagnostic and therapeutic applications

This thesis describes two different but related areas: intercalative thiazole orange (TO) probes and artificial DNA backbones. Thiazole orange (TO) is an asymmetric cyanine dye that is used to detect nucleic acids by fluorescence due to its intercalating characteristics, which results in an "on-off" fluorescent switch on binding to complementary nucleic acids. Modified nucleic acid backbones improve the half-lives of therapeutic oligonucleotides in vivo by conferring resistance to nuclease enzymic digestion. These two areas are both potentially important role in terms of diagnostic and therapeutic oligonucleotide properties.
The use of TO in various fluorogenic probe systems is described in this thesis. Phosphoramidite monomers based on a thymidine nucleoside with alkyne and amine modifications at the 5-position of the base, and with various lengths of amine linker (C3, C6) were designed for the orthogonal labelling of oligonucleotides at thymine sites. A single tube labelling technique was developed to functionalise the amino group via amide bond formation and the alkyne by CuAAC click chemistry (1,4-disubstituted 1,2,3- triazole formation). These new monomers were tested in oligonucleotide probes designed to facilitate fluorescence resonance energy transfer (FRET) between TO and a FRET acceptor/reporter dye (e.g. ROX) on binding to their complementary DNA or RNA targets. The steady state and time-resolved fluorescence properties of these modified oligonucleotides were investigated. Thermal duplex melting experiments revealed a beneficial increase in melting temperature (Tm) due to the presence of single or multiple thiazole orange dyes, whereas the reporter dye caused duplex destabilisation. These new combination probes were used to detect a SARS-COV-2 sequence in a LAMP (Loop- mediated isothermal amplification) assay where they provided good specificity and high sensitivity.
The synthesis and properties of oligonucleotides modified with triazole-locked nucleic acids (TL-LNA) were studied with antisense applications in mind. Triazole backbones are charge neutral five-atom connections that have previously been shown to be duplex destabilising, hence inappropriate for antisense applications. I show that the thermal stability of oligonucleotides containing the TL backbone bound to complementary RNA targets is improved when the triazole is combined with a locked nucleic acid sugar on the 3 ́-side of the triazole ring. TL-LNA nucleoside phosphoramidite dimers were synthesised to make the required oligonucleotide sequences. LNA-TLs of the kind produced in this study have more favourable properties than previous TL modifications.

Keywords: synthesis
modified oligonucleotides
Advisor: Brown, T
Trail ride nation: Zydeco music & Creole entanglements in Southwest Louisiana

This doctoral thesis brings into focus the connections between humans, non-humans and zydeco at trail rides in Southwest Louisiana and Eastern Texas. Creole trail rides have become spirited social occasions centered around horses, food, music and dancing. The transient, mobile nature of trail rides offers a unique opportunity to consider the power of human-nonhuman entanglements and their impact on social becoming and collective solidarity. I explore how the region’s ‘Trail Ride Nation’ has emerged from and is sustained by its human participants’ specific relationships with horses, sound, clothing and food. I ask: How can we understand human becoming, specifically ‘trail rider’ becoming, as an entanglement with non-human animals and materialities? Mindful of the complex racial history in Louisiana, I also address how these entangled relationships connect to understandings of ‘creolization’ as a process of ‘creation, invention, critique, and resistance’ (Cohen and Toninato 2010: 14), and I ask how can they can become tools for self-making and reinvention against the region’s historical backdrop of racial segregation and systems of exclusion. This thesis explores how encounters with non-humans can encourage communal action and what kind of common world emerges by way of sonic, sartorial and edible engagements. I aim to present an argument that the cultural identity and collective belonging that marks what it is to be a trail rider is constituted by these changing and dynamic relationships.

Keywords: race
Creole
non-human
horses
zydeco
Louisiana
music
trail ride
Advisor: Stanyek, J
Development and testing of ATLAS ITk strip barrel stave components

The LHC is planned to be upgraded to HL-LHC with a nominal luminosity of 5 × 10^34 cm^−2s^−1 and an operational lifetime of over 10 years. The ATLAS (A Toroidal LHC ApparatuS) experiment, as a general purpose particle physics experiment at the LHC, is planning a major upgrade in its tracker part to ensure performance in higher radiation and data rate. The new all-silicon inner tracker (ITk) is planned to be replacing the current SCT during the long shut down in 2026.
This thesis is focused on the strip barrel part of the ITk. It discusses the performance testing of different components on a strip barrel stave and the overall performance studies of a single stave. Pre-irradiation effect and operational parameters of ABCStar chip set are tested. The performance of a prototype ABCStar module in test beam is studied. This thesis discusses the software and procedure developments of the tape tester robot, which is developed for measuring strip barrel bus tapes. The statistical analysis of pre-production tape test results is obtained. The reliability studies of VTRx+ optical transceivers are also presented. This thesis also includes various studies on the performance of a single barrel stave.

Keywords: HL-LHC
hardware upgrade
ATLAS ITk
Advisor: Weidberg, A
Imagining the continent's future: China, India, and post-war Asia, 1937-1949

This thesis examines how in the late 1930s and 1940s leaders of China’s Nationalist Government and the Indian National Congress imagined post-war Asia and attempted to realise their ideas. Post-war Asia has been often understood in terms of nationalist movements without recognising how Asian leaders sought to shape their future on the Asian level. This thesis argues that China strategically sought an Asia where China would eventually be the dominant power; India aimed to, in some sense, create an Asia in its idealised self-image, where nations were relatively more equal in status. Both Chinese and Indian leaders supported the independence of Asian nations. Yet Chinese leaders thought that this would endanger the interests of the Chinese diaspora, while their Indian counterparts worried that new Asian nation-states could not defend themselves against the great powers. The Nationalist government insisted on diasporic Chinese being Chinese citizens and must be respected if not privileged by host governments; the Congress expected diasporic Indians to become naturalised citizens of host societies. Yet neither strategy resolved the discrimination diasporic communities faced. Decolonisation enabled majority national groups to enter into power but continued to marginalise minority groups. Both Nationalist China and Nehruvian India favoured planning and state-led industrialisation, but the Nationalists also anticipated China’s economic dominance in Asia. Moving beyond the perspective of superpower struggle, this thesis highlights China’s and India’s agency in shaping their region. Their ideas on Asia’s future were among the very first contributions from newly independent non-Western nations on how a post-war, post-colonial Asian state should be. Compared to the civilisational argument of early twentieth-century Pan-Asianism, Chinese and Indian leaders helped redefine Asia’s self-identity: from underdeveloped to prosperous and ‘modern’. Apart from the much-analysed border conflicts and geopolitical competition, the different visions for Asia helped contribute to the China-India divergence.

Keywords: decolonisation
Asianism
post-war
reconstruction
China-India relations
Asia
United Nations
India
development
Cold War
diaspora
Second World War
world-making
Asian Relations Conference
China
Advisor: Mitter, R
Church and state in late medieval England: the political activities of the English episcopate in the reign of Edward III

This thesis explores the political activities of the English episcopate in the reign of Edward III. It argues that bishops served the king in a variety of different ways during the mid-fourteenth century, as administrators, diplomats, military leaders, propagandists, parliamentarians, and financiers of the crown. Moreover, it highlights how their roles were of great importance for the king and his regime, and how prelates were well-positioned to perform them. However, it also shows that the involvement of bishops in politics did not merely serve the interests of the crown, but also those of the realm, the Church, and the prelates themselves. Nonetheless, the episcopacy was not obliged to support the king, and was indeed capable of opposing him, as was notably the case in the reigns of both Edward II and Richard II. As such, this thesis posits that Edward III’s kingship was not marked by an oppressive expansion of royal authority over pliant religious leaders, but rather by a successful alliance between ‘Church’ and ‘State’, which stands apart from the tumult, discontent, and quarrels of his father’s and grandson’s reigns.

Keywords: ecclesiastical history
Edward III
bishops
medieval history
political history
Advisor: Thompson, B