VictorJuiz/thesis huggingface dataset:
Development of catalytic methods to exploit sulfur dioxide in organic synthesis
Keywords: cross-coupling
palladium catalysis
DABSO
sulfur dioxide

In the following thesis, new methodologies towards the synthesis of a range of sulfonyl (-SO2-) containing functional groups are documented. These methods utilise easy-to-handle sulfur dioxide surrogates, such as DABSO (vide infra), and exploit palladium catalysis as a new mechanistic protocol for the incorporation of the -SO2- unit.
Chapter 1 is a literature review surveying sulfur dioxide in organic synthesis, the established uses of SO2 surrogates and the importance of the sulfonyl moiety in chemistry. Palladium-catalysed (carbonylative) cross-couplings are also broadly discussed as they provide inspiration for, and mechanistic similarities with, the proposed chemistry.
Chapter 2 describes a de novo synthesis of the sulfonamide functional group; a three-component and convergent methodology coupling (hetero)aryl and alkenyl halides with sulfur dioxide (provided by easy-to-handle surrogates such as DABSO) and hydrazine nucleophiles, is documented. This is achieved through the action of a readily available palladium catalytic system and is the first example of a metal-catalysed sulfonylative cross-coupling of halide based electrophiles.
Chapter 3 presents a new method of generating (hetero)aryl and alkenyl sulfones. The ability of organometallic reagents to add to sulfur dioxide (supplied via DABSO) is applied to deliver the corresponding metal sulfinate salt. This in situ derived sulfinate is coupled with an (hetero)aryl or alkenyl (pseudo)halide using palladium catalysis to form the desired sulfone. An electronically modified XantPhos-type ligand was designed for the reaction in order to suppress unwanted aryl-aryl exchange.
Chapter 4 documents the generation of (hetero)aryl and alkenyl sulfinates from the corresponding halide and DABSO through a palladium-catalysed sulfination protocol, obviating the need for organometallic reagents. A mild set of conditions using IPA as both a solvent and reductant together with a low loading of palladium catalyst offers an attractive route to sulfonyl compounds thanks to the in situ derived sulfinates being converted into a broad variety of functional groups via established onwards reactivity.
Chapter 5 discusses the conclusion of the research and the potential for future work.
Chapter 6 presents the experimental data.
Needle-free vaccination: formulation and dermal delivery of diphtheria toxin CRM197 mutant
Keywords: Spray freeze drying
CRM197
Needle-free
Vaccination
Hib
Hydroxyapatite
Nanoparticles

The unsafe use of needles propagates cross infections with bloodborne pathogens and reduces the positive impact of vaccinations on global health. While a plethora of needle-free injection devices exist, the reformulation of protein-based vaccines is largely empirical and costly, which presents a barrier to their widespread clinical application.
This thesis contributes to the identification of approaches that facilitate rapid vaccine reformulation and enhance the immunogenicity of needle-free dry-powder vaccines with the help of novel antigen delivery platforms.
We hypothesised that the thermodynamic stabilisation of diphtheria toxin mutant 197 (CRM197), a glycoconjugate vaccine carrier protein, may enhance its structural preservation during spray-freeze-drying (SFD), and that its formulation in either soluble, surface-adsorbed, or nanoparticle form impacts the elicited immune response. Differential scanning fluorimetry was used to study the effect of excipients on the thermal stability of CRM197. Dry-powder formulation of CRM197 used i) encapsulation into a thermodynamically stabilising excipient matrix by SFD, ii) surface-immobilisation via physisorption onto a novel potassium-doped hydroxyapatite (kHA) carrier microparticle formed by molten salt synthesis, and iii) chemical conjugation and surface presentation on amphiphilic block copolymer nanoparticles that were incorporated into SFD-powders (SFD-NP). The structural integrity of CRM197 was assessed by size separation in addition to various spectral and thermal analysis methods. The immunogenicity of dry-powder CRM197 formulations was subsequently tested in vivo.
The results suggest that the thermodynamic stability of CRM197 in solution does not ensure its structural stability during SFD. While needle-free dermal vaccination with kHA-adsorbed CRM197 induced comparable antibody titres to conventional IM injection of alum-adjuvanted CRM197, needle-free SFD and SFD-NP powders were less immunogenic. The highest mean IgG titre and most balanced Th1/Th2 response was achieved with nanoparticle-conjugated CRM197 by IM, which outperformed the current clinical standard.
Therefore, future vaccine design should combine thermodynamic and kinetic stability screening, and place special emphasis on the delivery and structural presentation of the antigen to the immune system.
Molecular and neural mechanisms of olfactory decision making in Drosophila melanogaster
Keywords: olfaction
Drosophila melanogaster
Decision-making

Traditional studies of simple perceptual choice tasks in vertebrates identified behavioural characteristics of deliberate decision-making that guided the development of general mathematical models, and the search for neurophysiological correlates. Current experimental and modelling efforts aim to uncover biophysical and circuit level mechanisms of decision-making processes. However, genetic manipulability constraints and lack of high-throughput assays make further progress in vertebrate studies a steep endeavour. In this thesis I studied decision-making in Drosophila melanogaster in trained two-alternative forced-choice olfactory tasks with varying stimulus contrast, using a high-resolution single fly behavioural assay. Analysing accuracy and reaction time as a function of task difficulty (i.e., stimulus contrast) showed that flies display behavioural characteristics of evidence accumulation processes, a signature of vertebrate decision-making: reaction times increased and perceptual accuracy declined as stimulus contrast decreased. Mutants for the gene encoding the transcription factor FoxP took longer than wild-type flies to form decisions of similar or reduced accuracy, especially in difficult tasks. Using the putative FoxP promoter to ascertain FoxP expression identified subsets of mushroom body intrinsic Kenyon cells, in αβ core and γ neurons, as potential sites of FoxP action. Disrupting FoxP expression or decreasing neuronal excitability specifically in αβ core neurons mimicked the phenotype observed in FoxP mutants. FoxP expression therefore affects the development or function of αβ core neurons in the progression of a decision process towards commitment. To identify molecular processes involved in evidence integration regulated by FoxP I further screened 2nd and 3rd chromosome deficiency lines in a sensitised FoxP mutant background, uncovering genomic regions of interest for further study. Finally, analysing naive performance in tasks of increasing difficulty showed that naive discriminations are faster and less accurate than trained ones, pointing to the existence of two decision-making systems. FoxP mutants appear to engage the slower, more accurate decision making system and the mushroom body seems to be involved in naive discriminations. The molecular and neuronal players involved in olfactory decision making in Drosophila melanogaster uncovered in this thesis will allow researching decision making systems to an unprecedented level of detail.
British responses to Du Bartas' Semaines, 1584-1641
Keywords: comparative literature -- French and English
French literature -- appreciation -- England
English literature -- French influences
1500-1700 -- history and criticism
literature -- translations into English -- history and criticism
imitation in literature
English poetry -- early modern

The reception of the Huguenot poet Guillaume de Saluste Du Bartas' Semaines (1578, 1584 et seq.) is an important episode in early modern literary history for understanding relations between Scottish, English and French literature, interactions between contemporary reading and writing practices, and developments in divine poetry. This thesis surveys translations (Part I), allusions and quotations in prose (Part II) and verse imitations (Part III) from the period when English translations of the Semaines were being printed in order to identify historical trends in how readers absorbed and adapted the poems. Early translations show that the Semaines quickly acquired political and diplomatic affiliations, particularly at the Jacobean Scottish Court, which persisted in subsequent decades (Chapter 1). William Scott's treatise The Model of Poesy (c. 1599) and translations indicate how attractive the Semaines' combination of humanist learning and sacred rhetoric was, but the poems' potential appeal was only realized once Josuah Sylvester's Devine Weeks (1605 et seq.) finally made the complete work available in English (Chapter 2). Different communities of readers developed in early modern England and Scotland once this edition became available (Chapter 3), and we can observe how individuals marked, copied out, quoted and appropriated passages from their copies of the poems in ways dependent on textual and authorial circumstances (Chapter 4). The Semaines, both in French and in Sylvester's translation, were used as a stylistic model in late-Elizabethan playtexts and Zachary Boyd's Zions Flowers (Chapter 5), and inspired Jacobean poems that help us to assess Du Bartas' influence on early modern poetry (Chapter 6). The great variety of responses to the Semaines demonstrates new ways that intertextuality was a constituent feature of vernacular religious literature that was being read and written in sixteenth- and seventeenth-century Britain.
On the dynamics of tidal streams in the Milky Way galaxy
Keywords: Milky Way
substructure
dynamics
galaxies
Tidal streams
The Galaxy

We present a brief history of Galactic astrophysics, and explain the origin of halo substructure in the Milky Way Galaxy. We motivate our study of the dynamics of tidal streams in our Galaxy by highlighting the tight constraints that analysis of the trajectories of tidal streams can place on the form of the Galactic potential. We address the reconstruction of orbits from observations of tidal streams. We upgrade the geometrodynamical scheme reported by Binney (2008) and Jin & Lynden-Bell (2007), which reconstructs orbits from streams using radial-velocity measurements, to allow it to work with erroneous input data. The upgraded algorithm can correct for both statistical error on observations, and systematic error due to streams not delineating individual orbits, and given high-quality but realistic input data, it can diagnose the potential with considerable accuracy. We complement the work of Binney (2008) by deriving a new algorithm, which reconstructs orbits from streams using proper-motion data rather than radial-velocity data. We demonstrate that the new algorithm has a similar potency for diagnosing the Galactic potential. We explore the concept of Galactic parallax, which arises in connection with our proper-motion study. Galactic parallax allows trigonometric distance calculation to stars at 40 times the range of conventional parallax, although its applicability is limited to only those stars in tidal streams. We examine from first principles the mechanics of tidal stream formation and propagation. We find that the mechanics of tidal streams has a natural expression in terms of action-angle variables. We find that tidal streams in realistic galaxy potentials will generally not delineate orbits precisely, and that attempting to constrain the Galactic potential by assuming that they do can lead to large systematic error. We show that we can accurately predict the real-space trajectories of streams, even when they differ significantly from orbits.
Hydrogen electrochemistry in room temperature ionic liquids
Keywords: adsorbed hydrogen atom
diffusion coefficient
proton reduction
room temperature ionic liquid
hydrogen evolution reaction
transition metal
tafel plot
electrochemistry
Butler Volmer equation
viscosity
transfer coefficient
rate constant
Shoup Szabo equation

This thesis primarily focuses on the electrochemical properties of the H2/H+ redox couple, at various metallic electrodes in room temperature ionic liquids. Initially, a comprehensive overview of room temperature ionic liquids, RTILs, compared to conventional organic solvents is presented which identifies their favourable properties and applications, followed by a second chapter describing the basic theory of electrochemistry. A third chapter presents the general experimental reagents, instruments and measurements used in this thesis. The results presented in this thesis are summarized in six further chapters and shown as follows.
(1) Hydrogenolysis, hydrogen loaded palladium electrodes by electrolysis of H[NTf2] in a RTIL [C2mim][NTf2].
(2) Palladium nanoparticle-modified carbon nanotubes for electrochemical hydrogenolysis in RTILs.
(3) Electrochemistry of hydrogen in the RTIL [C2mim][NTf2]: dissolved hydrogen lubricates diffusional transport.
(4) The hydrogen evolution reaction in a room temperature ionic liquid: mechanism and electrocatalyst trends.
(5) The formal potentials and electrode kinetics of the proton_hydrogen couple in various room temperature ionic liquids.
(6) The electroreduction of benzoic acid: voltammetric observation of adsorbed hydrogen at a Platinum microelectrode in room temperature ionic liquids.
The first two studies show electrochemically formed adsorbed H atoms at a metallic Pt or Pd surface can be used for clean, efficient, safe electrochemical hydrogenolysis of organic compounds in RTIL media. The next study shows the physicochemical changes of RTIL properties, arising from dissolved hydrogen gas. The last three studies looked at the electrochemical properties of H2/H+ redox couple at various metallic electrodes over a range of RTILs vs a stable Ag/Ag+ reference couple, using H[NTf2] and benzoic acid as proton sources. The kinetic and thermodynamic mechanisms of some reactions or processes are the same in RTILs as in conventional organic or aqueous solvents, but other remarkably different behaviours are presented. Most importantly significant constants are seen for platinum, gold and molybdenum electrodes in term of the mechanism of proton reduction to form hydrogen.
Logical constants
Keywords: modal logic
logical constants
uniqueness
substructural logics
analysis

[Abridged abstract] The goal is to give structural proof-theoretical analyses of logical constants, and thereby provide a criterion for what a logical constant is. Another goal is to illustrate the thesis that structural assumptions of logic are basic and that alternative logics (later called substructural logics) differ from each other only in their structural assumptions, and not in their assumptions about logical constants.
Writing exile: Fulvio Tomizza
Keywords: exile
Fulvio Tomizza
Istria
Italo-Croatian relationships
self-translation
plurilingualism

This thesis focuses on the unusual phenomenon of exile from a frontier land, as it is explored by the work of the Istrian writer Fulvio Tomizza. It deals with the diaspora from Istria, a territory at the intersection of different civilizations – the Italian and the Croat-Slovenian – which has historically shaped a mixture of cultures and languages, remarkable for its hybridity. The massive exile which took place at the end of the Second World War, after the redefinition of the Italo-Yugoslav border, presents original features which, by taking advantage of the narrative tool, overturn traditional parameters attributed to exile.
Focusing on Fulvio Tomizza’s novels Materada, La ragazza di Petrovia and L’albero dei sogni, and also on some of his most significant essays, I will seek to outline the specific traits that typify the detachment from one’s own native country. In particular, I shall suggest that identity and idioms are called into question even before characters have left their homeland. In addition, exile begins with a clarification of characters’ sense of belonging, which inevitably leads them to split, making the choice of whether to abandon the home country even more complicated. Once abroad, characters will develop a deep sense of estrangement, dictated by the impossibility of fitting into any other context, which will eventually drive them to a double, parallel, unsuccessful exile.
In order to investigate fully the characteristics of Fulvio Tomizza’s exile, I will employ some linguistic postulates to examine the bilingualism and diglossia of the origins. The theoretical approaches of Edward Said, Sigmund Freud and Julia Kristeva will be used to inform my analysis of the more subtle mechanisms which rule exile, starting with doubleness and examining the dynamics which commonly characterize the exilic experience, including those in relation to the elaboration of the narrative itself.
The novelty of this work lies in its approach to exile without preconceived arguments, which run the risk of limiting the analysis of the topic, and in the exploration of the most crucial aspects of a frontier land shaken by a territorial redefinition. This thesis also aims to reallocate the figure of Fulvio Tomizza, who has as yet not been investigated in any significant manner, most often being neglected or misunderstood. The aim is also to highlight one of the most European writers of the Italian second Novecento and his relationship with Eastern European languages and literatures.
Local impacts of natural resource booms and busts
Keywords: Natural Resources
Booms and Busts
Energy

This thesis consists of five stand-alone chapters empirically evaluating questions relating to the life cycle of natural resource extraction. We use three different data sets to shed light on the local impacts of natural resource booms and busts. In chapter 2 to 4 we use the household budget survey of Kazakhstan to explore the impacts of the oil boom on the local population. In the second chapter, we explore the distributional effects of the oil boom and show that average household income increased and income inequality decreased. In the third chapter we study how the increase in average income was perceived by the local population and find that households' satisfaction with income decreased. In the fourth chapter we study how the boom affected households' expenditure and show that the likelihood that households pay tuition fees for tertiary education increased. In chapter 5, we explore the long-term impacts of a negative labour demand shock following the coal mine closures in the UK. To do this we construct a new data set containing the location of all active coal mines since 1981 and link it to the UK census. We find that the dramatic lay off of miners since 1981 was associated with a persistent reduction in female labour force participation in the affected districts. In chapter 6, we study the determinants of drilling costs and their impact on the real price of oil using a new global data set on the number of exploration wells drilled and costs of drilling. To do this, we propose a structural model of the upstream sector in the oil and gas industry. The model allows us to decompose the variation in the reduced form errors of the estimated VAR into three structural shocks, and estimate the dynamic responses of the variables in the system to these shocks. We confirm that the upstream sector of the oil and gas industry is subject to increasing costs. But we do not find that the real oil price is permanently affected by shocks to costs of drilling.
Model selection strategies in genome-wide association studies
Keywords: genome-wide association studies
common diseases
model selection

Unravelling the genetic architecture of common diseases is a continuing challenge in human genetics. While genome-wide association studies (GWAS) have proven to be successful in identifying many new disease susceptibility loci, the extension of these studies beyond single-SNP methods of analysis has been limited. The incorporation of multi-locus methods of analysis may, however, increase the power of GWAS to detect genes of smaller effect size, as well as genes that interact with each other and the environment. This investigation carried out large-scale simulations of four multi-locus model selection techniques; namely forward and backward selection, Bayesian model averaging (BMA) and least angle regression with a lasso modification (lasso), in order to compare the type I error rates and power of each method. At a type I error rate of ~5%, lasso showed the highest power across varied effect sizes, disease frequencies and genetic models. Lasso penalized regression was then used to perform three different types of analysis on GWAS data. Firstly, lasso was applied to the Wellcome Trust Case Control Consortium (WTCCC) data and identified many of the WTCCC SNPs that had a moderate-strong association (p<10-5) type 2 diabetes (T2D), as well as some of the moderate WTCCC associations (p<10-4) that have since been replicated in a large-scale meta-analysis. Secondly, lasso was used to fine-map the 17q21 childhood asthma risk locus and identified putative secondary signals in the 17q21 region, that may further contribute to childhood asthma risk. Finally, lasso identified three potential interaction effects potentially contributing towards coronary artery disease (CAD) risk. While the validity of these findings hinges on their replication in follow-up studies, the results suggest that lasso may provide scientists with exciting new methods of dissecting, and ultimately understanding, the complex genetic framework underlying common human diseases.
Court-executive relations in unstable democracies: strategic judicial behaviour in post-authoritarian Argentina (1983-2005)
Keywords: Court-Executive relations
judicial activism
democracy
judicial independence
Executive branch
breakdowns
Argentina
Supreme Court
rational choice

This dissertation deals with court-executive relations in post-authoritarian Argentina (1983-2006). Specifically, I analyse Supreme Court behaviour in highly sensitive cases to determine whether the tribunal has cooperated with or obstructed the government’s policy preferences in three key policy areas: human rights, economic emergency and pensions. This innovative type of approach – i.e., focusing on a small number of highly sensitive decisions – allows me to concentrate on cases that are genuinely important for the government or, more precisely, for the country’s political administration. There are cases that are significant for the State apparatus but irrelevant for the president (thinking of politicians as self-interested actors).
My research uses a rational choice approach to courts, underscoring the strategic nature of judicial behaviour. This vision of judges provides a more accurate account of judicial-executive relations by bringing politics into the study of courts. By focusing exclusively on attitudes and apolitical jurisprudence, other visions take for granted the institutional context. Political stability, for example, cannot be assumed in many developing democracies.
My findings indicate that the Argentine Supreme Court has consistently avoided obstructing the president’s policy preferences. Such behaviour is motivated by strategic considerations: judges are risk-averse actors that avoid clashing with the executive. For most of the time, the Supreme Court has operated under unified government, which increases the chances of being punished for anti-government decisions. Two other factors also account for the court’s risk-averse behaviour. First, procedural rules grant the Supreme Court wide discretion over its docket. The tribunal has used such discretion to strategically select the timing of its decisions. Second, recurrent democratic breakdowns have repeatedly led to attacks against the court, such as impeachment, irregular dismissals, and/or enlargements. Third, politicians exert broad control of judicial promotions, allowing them to block the careers of independent, courageous judges that act as a check on political power.