VictorJuiz/thesis huggingface dataset:
Stability tests of opto-electronic systems for use in the SLHC
Keywords: SLHC
radiation
fibre optics
temperature

The Large Hadron Collider (LHC) located at CERN is the world’s most powerful particle accelerator, with plans to collide protons at a center of mass energy of 14 TeV. These proton-proton collisions occur within particle detectors located around the circumference of the accelerator. After approximately 10 years of running at this energy, the LHC accelerator will be upgraded to the super-LHC and it will be necessary to upgrade the constituent particle detectors, in particular the CMS and ATLAS detector experiments. The innermost layers of these detectors will have experienced a very high radiation environment over an extended period of time and will have reached the maximum radiation dose for which they were designed. Upgrades to the accelerator will increase the radiation dose rate and total dose experienced by the detectors, which will demand both increased radiation-hardness of detector components and improved detector performance to handle the increased data rate driven by accelerator upgrades.
This thesis presents results of tests performed as a part of the research and development of the LHC upgrade. In particular, we report on the optical fibres to be used in the readout systems of the inner detectors. Fibres were tested for performance variability in high radiation and temperature-variant environments.
The use of functionalised lithium amides in the total synthesis of alkaloids
Keywords: hoprominol
conjugate addition
hopromalinol
lithium amide
asymmetric synthesis
hopromine
morphine
homalium alkaloids
alkaloids
homaline

This thesis is concerned with the application of the conjugate addition of functionalised lithium amides in the asymmetric syntheses of (−)-morphine and all members of the homalium alkaloids. Chapter 1 introduces the conjugate addition reaction as an important bond forming reaction, and explores its utility in the asymmetric synthesis of a variety of natural products. The conjugate addition of secondary lithium amides derived from α-methylbenzylamine is discussed, along with its application to the asymmetric synthesis of alkaloids.
Chapter 2 describes two distinct attempts towards the asymmetric synthesis of (−)-morphine, both reliant upon the lithium amide conjugate addition and an intramolecular Diels-Alder reaction to set the five required stereogenic centres. The use of the novel and highly functionalised reagent lithium (R)-N-[2′-(7-methoxybenzofuran-3-yl)ethyl]-N-(α-methylbenzyl)amide and its derivatives is reported.
Chapter 3 focuses on the use of the novel reagent lithium (R)-N-(3-chloroprop-1-yl)-N-(α-methylbenzyl)amide and its derivatives in the asymmetric synthesis of two of the homalium alkaloids, (−)-(S,S)-homaline and (−)-(R,R)-hopromine, culminating in the most efficient syntheses of these alkaloids to date. Further, a sample of the (4′R,4′′S)-diastereoisomer of hopromine was synthesised, serving to confirm the proposed absolute configuration within natural (−)-(R,R)-hopromine.
Chapter 4 extends the methodology developed in chapter 3 to the asymmetric synthesis of all possible diastereoisomers of the remaining homalium alkaloids, (−)-hopromalinol and (−)-hoprominol. These syntheses were used to propose the absolute configurations within these alkaloids, and therefore represented the first asymmetric syntheses of natural (−)-(4′S,4″R,2‴R)-hopromalinol and (−)-(R,R,R)-hoprominol.
Chapter 5 contains full experimental procedures and characterisation data for all compounds synthesised in Chapters 2, 3 and 4.
Allele specific gene expression in the major histocompatibility complex
Keywords: eQTL
human genetics
allele-specific
gene expression
MHC

The Major Histocompatibility Complex (MHC) is a highly polymorphic region of the genome located on chromosome 6p21 in which genetic diversity has been associated with susceptibility to many autoimmune, infectious and other common diseases. Despite strong associations between disease and variation in the MHC that have been identified initially from serological testing and more recently by genome-wide association studies, functional insights into how specific variants may be altering disease susceptibility remain poorly understood in most cases. It is predicted that gene expression will play a significant role in the modulation of disease susceptibility and so further understanding of allele specific gene expression in the MHC will be necessary to help define the function of disease associated variants in this region.
This thesis aimed to define allele specific gene expression in the MHC by characterising specific candidate genes together locus-wide approaches in order to try and resolve functional variants. Gene expression was analysed in both lymphoblastoid cell lines (LCLs) and primary human peripheral blood mononuclear cells (PBMCs). Data is presented validating a novel haplotype-specific MHC microarray and fine mapping putative local, likely cis-acting, regulatory variants. This was done by expression quantitative trait mapping for two cohorts of healthy volunteers. A transcription factor ZFP57, encoded in the MHC, was found to show significant differential allelic expression relating to specific single nucleotide polymorphisms (SNPs) and possession of HLA-type. This provided new insights into reported disease associations, notably HIV-1 infection and cancer. The function of ZFP57 was further investigated in terms of genome-wide DNA binding sites by ChIP-seq together with its binding co-factor KAP1.
Allele-specific gene expression was also demonstrated for several classical HLA genes including the HLA-C and HLA-DQ genes, fine mapping specific putative regulatory variants. This provided new insights into disease association, notably variants of HLA-DQB1 and susceptibility to leprosy. The applicability and sensitivity of the technique of RNA sequencing (mRNA-seq) for allele-specific quantification of gene expression was investigated for different allelic ratios of RNA from LCLs homozygous for sequence across the MHC. Significant challenges were identified in successful application of this technique to MHC genes while high levels of accuracy were observed dependent on read depth in non-MHC genes.
This thesis provides new insights into the extent and nature of allele-specific gene expression in the MHC, experimental approaches that can be used and insights gained into disease susceptibility for this important genomic region.
Magnetic field effects in chemical systems
Keywords: MARY
ODEPR
electron spin resonance
regularization
anisotropic
RF
MFE
zero-field EPR
Wiltschko
electron paramagnetic resonance
magnetoreception
Maximum Entropy
Tikhonov
semiclassical
magnetic
MARY-B0
RPM
ESR
Erithacus rubecula
MARY-nu
magnetic field effect
polarization
Ritz

Magnetic fields influence the rate and/or yield of chemical reactions that proceed via spin correlated radical pair intermediates. The field of spin chemistry centres around the study of such magnetic field effects (MFEs). This thesis is particularly concerned with the effects of the weak magnetic fields B₀ ~ 1mT relevant in the ongoing debates on the mechanism by which animals sense the geomagnetic field and on the putative health effects of environmental electromagnetic fields. Relatively few previous studies have dealt with such weak magnetic fields. This thesis presents several new theoretical tools and applies them to interpret experimental measurements. Chapter 1 surveys the development and theory of spin chemistry. Chapter 2 introduces the use of Tikhonov and Maximum Entropy Regularisation methods as a new means of analysing MARY field effect data. These are applied to recover details of the diffusive motion of reacting pyrene and N,N-dimethylaniline radicals. Chapter 3 gives a fresh derivation and appraisal of an approximate, semiclassical approach to MFEs. Monte Carlo calculations allow the elucidation of several "rules of thumb" for interpreting MFE data. Chapter 4 discusses recent optically-detected zero-field EPR measurements, adapting the gamma-COMPUTE algorithm from solid state NMR for their interpretation. Chapter 5 explores the role of RF polarisation in producing MFEs. The breakdown in weak fields of the familiar rotating frame approximation is analysed. Chapter 6 reviews current knowledge and landmark experiments in the area of animal magnetoreception. The origins of the sensitivity of European robins Erithacus rubecula to the Earth’s magnetic field are given particular attention. In Chapter 7, Schulten and Ritz’s hypothesis that avian magnetoreception is founded on a radical pair mechanism (RPM) reaction is appraised through calculations in model systems. Chapter 8 introduces quantitative methods of analysing anisotropic magnetic field effects using spherical harmonics. Chapter 9 considers recent observations that European robins may sometimes be disoriented by minuscule RF fields. These are shown to be consistent with magnetoreception via a radical pair with no (effective) magnetic nuclei in one of the radicals.
Historical argument in the writings of the English deists
Keywords: Heterodoxy
Deists
John Toland
Probability
Divine Attributes
Things Above Reason
William Whiston
Natural Religion
Anthony Collins
Deism
Samuel Clarke
Revealed Religion
Thomas Morgan
Matthew Tindal
Thomas Chubb
Enlightenment
William Warburton

This study examines the role of history in the writings of the English deists, a group of heterodox religious controversialists who were active from the last quarter of the seventeenth century until the middle of the eighteenth century. Its main sources are the published works of the deists and their opponents, but it also draws, where possible, on manuscript sources. Not all of the deists were English (one was Irish and another was of Welsh extraction), but the term ‘English Deists’ has been used on the grounds that the majority of deists were English and that they published overwhelmingly in England and in English. It shows that the deists not only disagreed with their orthodox opponents about the content of sacred history, but also about the relationship between religious truth and historical evidence.
Chapter 1 explains the entwining of theology and history in early Christianity, how the connection between them was understood by early modern Christians, and how developments in orthodox learning set the stage for the appearance of deism in the latter decades of the seventeenth century. Each of the following three chapters is devoted to a different line of argument which the deists employed against orthodox belief. Chapter 2 examines the argument that certain propositions were meaningless, and therefore neither true nor false irrespective of any historical evidence which could be marshalled in their support, as it was used by John Toland and Anthony Collins. Chapter 3 traces the argument that the actions ascribed to God in sacred history might be unworthy of his goodness, beginning with Samuel Clarke’s first set of Boyle Lectures and then progressing through the writings of Thomas Chubb, Matthew Tindal, Thomas Morgan, and William Warburton. Chapter 4 charts the decline of the category of certain knowledge in the latter half of the seventeenth century, the rise of probability theory, and the effect of these developments on the deists’ views about the reliability of historical evidence. Chapter 5 is a case-study, which reads Anthony Collins’s Discourse of the Grounds and Reasons of the Christian Religion (1724) in light of the findings of the earlier chapters. Finally, a coda provides a conspectus of the state of the debate in the middle decades of the eighteenth century, focusing on the work of four writers: Peter Annet, David Hume, Conyers Middleton, and Edward Gibbon.
Nationalism, cosmopolitanism and empire in Britain's American expatriate community, c.1815–1914.
Keywords: US foreign relations - nineteenth century
transnationalism - history
American communities overseas - Britain
nationalism

This study examines the coalescence of American expatriate communities in Britain between 1815 and 1914. Blending transnational and post-colonial approaches to US history, this dissertation explores the nuanced roles of Americans in Britain as intermediaries in the consolidation of US independence, the formation of American nationalism, and the emergence of American empire.
Transatlantic economic and cultural connections converged in American communities in Britain. The American communities of London and Liverpool evolved and dissolved around these rapidly transforming interconnections. These communities are recaptured in this study from scattered archives on both side of the Atlantic. The Antebellum American community acted as a conduit between British capital and American nation-building projects and promoted transatlantic rapprochement as the route to effective US independence. The importation of American innovation and manufactured goods into Britain and the Empire, however, followed late nineteenth-century expatriates. As US power surged, Americans in London created a self-identifying American “colony,” which acted as the interface between US economic and cultural expansion and British imperialism.
Throughout the century, Britain’s American communities acted as crucibles in which sectional, national, and racial identifications were contested and reconstructed. Expatriate newspapers, celebrations, and social institutions, provided the venues for Americans in Britain to articulate and reformulate American nationalism. In the context of British power, the contestations and reformulations of these identities were bled through with post- and anti-colonial anxieties. Expatriates therefore acted as avatars for sharpening distinctions between the US and Britain in debates over the form of American national character, culture, and empire – and Britain’s role in all three.
This study reframes these themes around the previously overlooked communities of Americans in Britain. From these communities, which stand at the intersection of US and British Imperial history, a new perspective emerges on the reciprocal dynamics of nationhood and empire in nineteenth century Anglo-American relations.
Immobilisation and application of bifunctional iminophosphorane organocatalysts
Keywords: bifunctional organocatalysis
solid-supported catalysts

Bifunctional iminophosphoranes, containing a triaryl-substituted iminophosphorane and bis(3,5- trifluoromethyl)phenyl thiourea on a single enantiomer scaffold are novel asymmetric superbase organocatalysts reported by the Dixon group in 2014. This thesis describes our efforts to expand their scope and utility in a variety of challenging chemical transformations.
Chapter 2 describes the development and application of immobilised bifunctional iminophosphorane organocatalysts. We have successfully immobilised bifunctional iminophosphoranes on a crosslinked polystyrene support and applied this sold-supported catalyst to three challenging asymmetric reactions; namely the nitro-Mannich reaction of phosphinoyl ketimines and the conjugate addition of alkylmalonates and N,N-dimethyl β-keto amides to nitrostyrene. Very good yields, enantio- and diasteroselectivities were obtained in all cases. We have also demonstrated their use in a range of conjugate additions of cyclic 1,3-dicarbonyl compounds to nitroalkenes, which suffered from very slow reaction rates under tertiary amine-based bifunctional catalysis. In all cases, the immobilised bifunctional iminophosphoranes performed very well in comparison to their homogeneous counterparts. We have also demonstrated catalyst recycling over 10 cycles and application in a continuous flow system with a productivity of 7.20 mmol producth-1gcatalyst-1.
to the ring-opening polymerisation (ROP) of cyclic esters. We have demonstrated the performance of bifunctional iminophosphorane organocatalysts in the ROP of L-lactide (LA), δ-valerolactone (VL) and ε-caprolactone (CL). The polymerisation of LA and VL proceeded rapidly and was well controlled, while only short lengths (> 100 DP) of poly(CL) could be prepared in a controlled fashion due to hypothesised competing initiation from the catalyst. We have shown that the polymerisation of LA using our catalyst may be considered a living polymerisation. Di-block co-polymers could also be successfully prepared via sequential monomer addition or through the use of macroinitiators. We then investigated the roles of the iminophosphorane and the thiourea component of the catalyst.
Epigenetic regulation of the myeloid cell lineage
Keywords: cancer
multiple myeloma
macrophages
Epigenetics
Immunology

The myeloid cell lineage is a fundamental element of the immune system and it can give rise to a diverse set of terminally differentiated cells, such as macrophages or osteoclasts among many others. Mutations or misregulation of gene expression may lead to severe clinical conditions, such as arthritis, osteoporosis or cancers. Epigenetics, the regulation of gene expression and chromatin remodelling, is implicated in cell differentiation, function and disease, and hence it is a promising new area to explore in order to explain underlying cellular mechanisms.
Firstly, human macrophage subtypes were studied. Chemokine (C-C motif) ligand (CCL) 1 and mannose receptor were validated to be granulocyte macrophage (GM) colony stimulating factor (CSF) induced macrophage markers, while CCL2 was specifically expressed in macrophage CSF (MCSF) macrophage population. By utilising publicly available high-throughput sequencing data, new biomarkers dehydrogenase/reductase (SDR family) member 2 and CCL26 were discovered to be MCSF-macrophage specific while guanylate binding protein 5 and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A were highly up-regulated in GMCSF cells.
Secondly, a range of gene knock-down techniques for the myeloid cell lineage were optimised and established. Lentiviral short-hairpin RNA (shRNA) delivery methods were shown to induce an undesirable pro-inflammatory response in macrophages. Furthermore, the frequently utilised cytomegalovirus promoter for gene expression was shown to be completely silenced in macrophage populations. Locked nucleic acids were selected as a suitable alternative to shRNA knock-down and by employing this new tool it was shown that a histone demethylase lysine (K)-specific demethylase (KDM) 6B is fundamental for macrophage differentiation.
Finally, a small molecule GSK-J4, a potent inhibitor of histone demethylases KDM6A, KDM6B and KDM5B specific for H3K27me3 and H3K4me3, respectively, was used to dissect epigenetic signalling in osteoclasts and multiple myeloma. In osteoclasts it was shown to act mainly by inhibiting transcriptional changes required for osteoclastogenesis when MCSF-macrophages are stimulated with Receptor Activator Of Nuclear Factor Kappa-B Ligand (RANKL), as indicated by the differential increase in H3K27me3 marks, leading to inhibition of c-Jun and potentially abolition of transcription factor AP-1, required for the transcriptional initiation of nuclear factor of activated T-cells 1 (NFATc1). In multiple myeloma cells, GSK-J4 causes a dramatic increase in expression, further supported by the build-up of global H3K4me3 marks, which results in the upregulation of the unfolded protein response pathway. In both cell systems, there is an early upregulation of metallothionein genes, which in multiple myeloma was shown to increase potentially due to rapid influx of zinc ions within the first 30 minutes, and as such may cause induction of apoptosis in multiple myeloma and may inhibit differentiation of osteoclasts.
Topics in monitoring and planning for embedded real-time systems
Keywords: antichains
real-time logics
monitoring
computational complexity
expressiveness
UAV

The verification of real-time systems has gained much interest in the formal verification community during the past two decades. In this thesis, we investigate two real-time verification problems that benefit from the techniques normally used in untimed verification.
The first part of this thesis is concerned with the monitoring of real-time specifications. We study the expressiveness of metric temporal logics over timed words, a problem that dates back to early 1990s. We show that the logic obtained by extending Metric Temporal Logic (MTL) with two families of new modalities is expressively complete for the Monadic First-Order Logic of Order and Metric (FO[<,+1]) in time-bounded settings. Furthermore, by allowing rational constants, expressive completeness also holds in the general (time-unbounded) setting. Finally, we incorporate several notions and techniques from LTL monitoring to obtain the first trace-length independent monitoring procedure for this logic.
The second part of this thesis concerns a decision problem regarding UAVs: given a set of targets (each ascribed with a relative deadline) and flight times between each pair of targets, is there a way to coordinate a flock of k identical UAVs so that all targets are visited infinitely often and no target is ever left unvisited for a time longer than its relative deadline? We show that the problem is PSPACE-complete even in the single-UAV case, thereby corrects an erroneous claim from the literature. We then complement this result by proposing an efficient antichain-based approach where a delayed simulation is used to prune the state space. Experimental results clearly demonstrate the effectiveness of our approach.
Behavioural responses to photovoltaic systems in the UK domestic sector
Keywords: energy policy
UK
photovoltaics
consumer behaviour

Microgeneration technologies, such as solar photovoltaics (PV), have recently been cited as a potential solution to energy policy challenges such as climate change and security of supply. International evidence suggests that the benefit of a PV installation will depend on both the amount of electricity generated and the technology’s influence on energy consumption behaviour. This study seeks to quantify and explain this ‘double-dividend’ effect by examining photovoltaics in the UK domestic sector.
Questionnaire and interview data were collected from owner-occupier PV households, revealing that the installation of PV increased awareness of electricity generation and consumption in the home. Guided by monitoring devices, an overall electricity saving (~8%) and load-shifting behaviours were observed. Although the installation of PV followed a series of other energy-saving measures, respondents showed an ongoing commitment to environmentally responsible behaviour and further reduction of the carbon footprint of household energy consumption. PV household electricity data and interviews with industry and government found that electricity tariffs, metering and other institutional constraints were important determinants of a household’s behavioural response. As these parts of the domestic PV system are largely still evolving, it is recommended that households and industry work together to develop systems that support sustainable electricity use, for both the early adopting households studied here and future adopters.