VictorJuiz/thesis huggingface dataset:
Investigating the chemistry of cationic rhodium bisphosphine complexes: comparing reactivity in the solid state with solution
Keywords: Catalysis
Organometallic
Alkane complex
Arene complex
Solid state
Rhodium
Phosphine

This thesis describes the synthesis and characterisation of a series of cationic rhodium bis-phosphine complexes. The reactivity of these new complexes in the solid-state and in solution is reported.
In Chapter 2 the synthesis of a series of rhodium bis-phosphine diene complexes is presented and the reactions of these complexes with hydrogen in the solid-state are investigated. Several examples of zwitterionic complexes coordinating the [BArF4]─ anion are produced by hydrogenation. A rare example of a sigma-alkane complex, [Rh(iBu2PCH2CH2PiBu2)(eta2-CH-eta2-CH-NBA][BArF4]─
iBu2PCH2CH2PiBu2)(eta2-CH-eta2-CH-NBE][BArF4] may form as a short lived intermediate prior to the formation of the sigma-alkane complex. The temporal evolution of the solid-state hydrogenation reactions is monitored by powder X-ray diffraction methods.
In Chapter 3 the C−X activation of various aryl halides using the [Rh(iBu2PCH2CH2PiBu2)]+ fragment is reported. The 'ligand innocence' of the phosphine with respect to intramolecular C−H activation is also discussed. A rare example of C−X activation in the solid-state is presented, which shows the formation of an isomer that is not observed by analogous solution routes.
Chapter 4 investigates solid-state ligand exchange reactions using ethene, butadiene, CO and NH3 gases. A solid-state transfer dehydrogenation reaction is reported within single crystals of [Rh(iBu2PCH2CH2PiBu2)(C2H4)2][BArF4]. H/D exchange of NH3 can also occur in the solid state in the bis-ammonia complex [Rh(iBu2PCH2CH2PiBu2)(NH3)2][BArF4]. A variety of rhodium complexes are tested as heterogeneous catalysts for the hydrogenation of ethene and the isomerisation of butene.
In Chapter 5 the binding affinity of a variety of fluorinated arenes to rhodium bis-phosphine fragments is presented using ESI-MS methods. The dependence upon the arene substituents, phosphine substituents and phosphine bite angle are discussed.
Topics in analytic number theory
Keywords: Analytic number theory

In this thesis we prove several results in analytic number theory.
1. We show that there exist 3-digit palindromic primes in base b for a set of b having density 1 and that if b is sufficiently large then there is a 3
-digit palindrome in base b having precisely two prime factors.
2. We prove various estimates for averages of sums of Kloosterman fractions over primes. The first of these improves previous results of Fouvry-Shparlinski and Baker.
3. By using the q-analogue of van der Corput's method to estimate short Kloosterman sums we study the divisor function in an arithmetic progression to modulus q. We show that the expected asymptotic formula holds for a larger range of q than was previously known, provided that q has a certain factorisation.
4 Let ‖x‖ denote the distance from x to the nearest integer. We show that for any irrational α and any ϴ< 8/23 there are infinitely many n which are the product of two primes for which ‖nalpha‖ ≤ n -ϴ.
5. By establishing an improved level of distribution we study almost-primes of the form f(p,n) where f is an irreducible binary form over Z.
6. We show that for an irreducible cubic f ? Z[x] and a full norm form mathbfN
for a number field K/Q
, satisfying certain hypotheses, the variety
f(t)=mathbfN(x1,ldots,xk)e0
satisfies the Hasse principle. Our proof uses sieve methods.
The histone deacetylase inhibitor panobinostat as a radiosensitiser in bladder cancer
Keywords: panobinostat
bladder cancer
HDAC inhibitors
radiosensitisation

Muscle invasive bladder cancer (MIBC) has a poor prognosis. Currently, therapy consists of radical radiotherapy or cystectomy with or without chemotherapy. The average age of patients with MIBC is high and older patients are less able to tolerate surgery or chemoradiation due to their impaired physical fitness and generally poor renal function. There is an urgent need to find new treatment regimes that are both tolerable and effective.
The HDAC inhibitor panobinostat was found to be toxic in the low nanomolar range and significant radiosensitising effects were demonstrated at doses lower than IC50 in all the bladder cell lines studied. The radiosensitising effect of panobinostat was not influenced by TP53 status, which is generally regarded as an important determinant of bladder cancer response to radiotherapy. In the “synthetic lethality” bladder cancer cell model, panobinostat predominantly targets the HR pathway, reportedly the only proficient DNA repair pathway in MIBC. HR proteins RAD51 and CtIP were downregulated upon panobinostat treatment in a dose-dependent manner. Upstream, MRE11 and NBS1 proteins were also targeted by panobinostat, with levels slightly decreased in RT112 and T24 cells and in CAL29 cells post-ionising radiation.
In summary, the HDAC inhibitor panobinostat was shown to be an efficient radiosensitiser in bladder cancer cells at low toxic doses and to predominantly target the HR pathway. These findings are promising and may contribute towards establishing a novel combination therapy of panobinostat with IR for MIBC patients.
Ceramic processing of magnesium diboride
Keywords: superconductivity
magnesium diboride
ceramic processing
ceramics

This thesis describes the fabrication and characterization of ex situ magnesium diboride (MgB2) bulk material to study its sintering behaviour. Since the discovery of superconductivity in magnesium diboride in 2001, many research studies have identified the attractive properties of this easy-to-fabricate, low cost superconductor which can attain high critical current density even without heat-treatment. However there is little consensus in the literature on the processing requirements to produce high quality MgB2 material with low impurity content and high density. In this work, the key parameters in the production of dense ex situ MgB2 produced from Alfa Aesar MgB2 powder are established by examining the effect of modifying the characteristics of the starting material and the processing parameters during pressureless and pressure assisted heat-treatment.
The particle size distribution, impurity content and particle morphology of Alfa Aesar MgB2 powder were determined using laser dffraction, X-ray diffraction, X-ray photoelectron spectroscopy, electron dispersive spectroscopy, scanning electron microscopy and transmission electron microscopy. This powder was also modified by separation (sieving and sedimentation) and milling (ball milling and attrition milling), with changes made to the powder determined by the same techniques.
A pressureless heat-treatment method using a magnesium diboride powder bed was developed. This minimised MgO formation in samples produced from as-purchased MgB2 powder to less than 8 wt.% for heat-treatment at 1100°C. MgO content was determined by X-ray diffraction using calibrated standards. MgB2 bulk material was produced from as-purchased and modified powders by pressureless heat-treatment under Ar gas, and characterized using Archimedes' density method, X-ray diffraction, Vickers hardness testing, scanning electron microscopy, and magnetization measurements. Very limited densification was observed for all samples prepared by pressureless heat-treatment, with only limited increases in connectivity observed for some samples heat-treated at 1100°C.
Pressure-assisted bulk samples were prepared from as-purchased MgB2 and selected modified powders using resistive sintering, spark plasma sintering, and hot pressing. These were characterized using the same techniques, which indicated much more extensive densification with similar levels of impurity formation as for pressureless heat-treatment at 1100°C. The results indicate that densification and applied pressure are strongly correlated, while the effect of temperature is less significant. The optimum processing environment (inert gas or vacuum) was dependent on the technique used. These results indicate that pressure-assisted heat-treatment is required in order to produce dense bulk MgB2.
Statistical models for neuroimaging meta-analytic inference
Keywords: Gaussian processes
neuroimaging
FMRI
pain perception
neuroscience
parametric and nonparametric inference
Bayesian inference
meta-analysis

A statistical meta-analysis combines the results of several studies that address a set of related research hypotheses, thus increasing the power and reliability of the inference. Meta-analytic methods are over 50 years old and play an important role in science; pooling evidence from many trials to provide answers that any one trial would have insufficient samples to address. On the other hand, the number of neuroimaging studies is growing dramatically, with many of these publications containing conflicting results, or being based on only a small number of subjects. Hence there has been increasing interest in using meta-analysis methods to find consistent results for a specific functional task, or for predicting the results of a study that has not been performed directly. Current state of neuroimaging meta-analysis is limited to coordinate-based meta-analysis (CBMA), i.e., using only the coordinates of activation peaks that are reported by a group of studies, in order to "localize" the brain regions that respond to a certain type of stimulus. This class of meta-analysis suffers from a series of problems and hence cannot result in as accurate results as desired.
In this research, we describe the problems that existing CBMA methods are suffering from and introduce a hierarchical mixed-effects image-based metaanalysis (IBMA) solution that incorporates the sufficient statistics (i.e., voxel-wise effect size and its associated uncertainty) from each study. In order to improve the statistical-inference stage of our proposed IBMA method, we introduce a nonparametric technique that is capable of adjusting such an inference for spatial nonstationarity. Given that in common practice, neuroimaging studies rarely provide the full image data, in an attempt to improve the existing CBMA techniques we introduce a fully automatic model-based approach that employs Gaussian-process regression (GPR) for estimating the meta-analytic statistic image from its corresponding sparse and noisy observations (i.e., the collected foci). To conclude, we introduce a new way to approach neuroimaging meta-analysis that enables the analysis to result in information such as “functional connectivity” and networks of the brain regions’ interactions, rather than just localizing the functions.
Chemical scanning probe lithography and molecular construction
Keywords: self assembled monolayer
AFM
scanning probe lithography
biopatterning
nanofabrication
nanolithography

The initiation and high resolution control of surface confined chemical reactions would be both beneficial for nanofabrication and fundamentally interesting. In this work, spatially controlled scanning probe directed organometallic coupling, patterned functional protein immobilisation and highly localised reversible redox reactions on SAMs were investigated.
Catalytically active palladium nanoparticles were mounted on a scanning probe and an appropriate reagent SAM was scanned in a reagent solution. This instigated a spatially resolved organometallic coupling reaction between the solution and SAM-phase reagents. Within this catalytic nanolithography a spatial resolution of ~10nm is possible, equating to zeptomole-scale reaction. The methodology was applied to reactions such as Sonogashira coupling and local oligo(phenylene vinylene) synthesis. By altering the experimental protocols, relating probe scan velocity to reaction yield and characterising the nanopattern, a PVP matrix model describing a proposed mechanism of catalytic nanolithography, was presented. Though ultimately limited by probe deactivation, calculations indicated that activity per immobilised nanoparticle is very high in this configuration.
For biopatterning, surface nanopatterns defined by carboxylic functionality were generated from methyl-terminated SAMs by local anodic oxidation (LAO) initiated by a conductive AFM probe. By employing suitable linker compounds, avidin and Stefin-A quadruple Mutant (SQM) receptive peptide aptamers were patterned at sub-100nm resolution. The multiplexed sensing capability of an SQM array was demonstrated by reacting generated patterns with single or a mixture of multiple antibodies.
The reversible redox conversion and switching of reactivity of hydroquinone-terminated SAMs was electrochemically demonstrated prior to an application in redox nanolithography. In this methodology, spatially controlled probe-induced in situ "writing" and "erasing" based on reversible redox conversion were conducted on hydroquinone terminated SAM. In combination with dip-pen nanolithography, a novel method of redox electro-pen nanolithography was designed and the method’s application for lithography was examined.
Characterisation of 2-oxoglutarate- and fe(II)-dependent oxygenases targeting the protein synthesis apparatus
Keywords: ribosome
translational termination
post-translational modification
oxygen sensing
protein synthesis

Members of the 2-oxoglutarate (2OG)- and Fe(II)-dependent oxygenase (2OG oxygenase) superfamily catalyse a wide range of oxidative reactions in biology. 2OG oxygenases require Fe(II) and atmospheric oxygen for their activity, and couple substrate oxidation with the decarboxylation of 2OG into succinate and carbon dioxide. There are more than sixty known 2OG oxygenases in the human genome; they modify small molecules, nucleic acids and proteins implicated in diverse biological processes.
Importantly, the seemingly disparate functions of 2OG oxygenases often converge to regulate gene expression. 2OG oxygenases have been shown to affect epigenetic reprogramming, chromatin remodelling, transcription factor activity and mRNA splicing. Emerging evidence indicates that 2OG oxygenases are also involved in the translational control of gene expression. Oxygenases TYW5, ALKBH8, ALKBH5 and FTO were found to catalyse modifications of tRNA and mRNA. The work in this thesis extends these observations by demonstrating that 2OG oxygenase-catalysed protein hydroxylations also play an important role in protein synthesis. The catalytic activities of two oxygenases belonging to the JmjC-only family, NO66 and JMJD4, are described. NO66 catalyses the histidinyl hydroxylation of 60S ribosomal subunit protein L8. NO66 is part of a conserved group of ribosomal protein hydroxylases that can be traced back to prokaryotes. JMJD4 is a lysyl hydroxylase of eRF1, the eukaryotic release factor responsible for translation termination. The hydroxylation of eRF1 takes place on a conserved NIKS motif important for release factor activity, and promotes effcient translational termination. JMJD4 is further implicated in cell growth and cancer, though the link between its activity and tumourigenesis remains to be determined. These results highlight the potential of 2OG oxygenases as regulators of protein synthesis, and further extend the scope of 2OG oxygenase function. The small molecule inhibition of 2OG oxygenases presents a novel therapeutic possibility targeting translational control in cancer and other diseases.
In vitro analysis of viral fusion and receptor binding with a focus on selected arthropod-borne viruses of the families Bunyaviridae and Togaviridae
Keywords: Electron cryotomography
Icosahedral reconstruction
Electron cryomicroscopy
DC-SIGN
Phlebovirus
Alphavirus
Virus entry
Semliki Forest virus
Membrane fusion
Uukuniemi virus
Bunyaviridae

Emerging arthropod-borne viruses, such as alphaviruses and bunyaviruses, represent a serious threat to human and animal health worldwide, and for most of them, vaccines and specific treatments are unavailable. Viral host cell entry can be divided into several entry checkpoints, and the most important checkpoints for low pH-dependent enveloped viruses, such as bunyaviruses and alphaviruses, include receptor binding at the cell surface and, followed by endocytosis, low pH dependent membrane fusion from within intracellular compartments. A more thorough understanding of the detailed mechanisms allowing the viruses to pass these checkpoints is a pre-requisite for the design of viral entry inhibitors.
This thesis reports the in vitro analysis of native alphavirus-receptor interactions, with the help of electron cryo-microscopy and icosahedral reconstruction of virus-recaptor complexes, using the prototypic alphavirus Semliki Forest virus (SFV) and the C-type lectin DC-SIGN. Together with results from collaborative work on SFV glycosylation, this study provides progress in defining the binding sites of DC-SIGN at the surface of SFV.
Second, an in vitro system for phlebovirus fusion was developed using standard fluorometry, and has been characterized with the help of electron cryo-microscopy. It was discovered that negatively charged phospholipids with a conical shape, including the late endosomal phospholipid BMP, allow efficient phlebovirus fusion in vitro, thereby providing a possible rationale for phlebovirus fusion in late endosomes. Furthermore, electron cryo-microscopy of phlebovirus-liposome complexes allowed the capture of early stage fusion intermediates and laid the basis for possible future higher resolution studies of these fusion intermediates.
Community, Self-Help and Mutual Aid: Friendly Societies and the Parish Welfare System in Rural Oxfordshire, 1834-1918
Keywords: Welfare
Oxfordshire
Clothing Club
Friendly Society
Stonesfield
Philanthropy
Welfare System
Clubs
Coal Club
Nursing Association
Social Welfare
Parish
Whitchurch
Soup Kitchen
Medical Aid Club
Friendly Societies

This thesis examines welfare provision in rural Oxfordshire after the 1834 Poor Law Amendment Act. The county had little industrial development, remained largely agricultural in nature, and the region had been perceived as a backwater of friendly society development.
This thesis rectifies that view and places Oxfordshire as an important component of the movement with its independent nature and early rejection of affiliated order branches that emanated from urbanized and industrialized areas. There is no evidence of impetus given to friendly society formation after the implementation of the new poor law with the general increase in societies continuing. However, the relationship with poor law administration changed. A case study of Stonesfield demonstrates how the friendly society became the heart of village life and was integral to self help and support for the poor.
A wider view is taken of welfare provision, with detailed assessment of a range of welfare instruments, such as coal and clothing clubs, soup kitchens, and medical clubs, together with an appraisal of their geographical spread. The range of welfare instruments available is compared to Maslow’s Hierarchy of Need, a model of human motivation. The case study of Whitchurch provides an in-depth assessment of one parish welfare system where after 1834 at least nine stands of welfare were available at all times to the poor who held a degree of selection in what was an increasingly a consumer market. The thesis is underpinned throughout by the use of extensive primary source material.
Saturation methods for global model-checking pushdown systems
Keywords: temporal logic
verification
model-checking
higher-order pushdown automata
pushdown automata

Pushdown systems equip a finite state system with an unbounded stack memory, and are thus infinite state. By recording the call history on the stack, these systems provide a natural model for recursive procedure calls. Model-checking for pushdown systems has been well-studied. Tools implementing pushdown model-checking (e.g. Moped) are an essential back-end component of high-profile software model checkers such as SLAM, Blast and Terminator.
Higher-order pushdown systems define a more complex memory structure: a higher-order stack is a stack of lower-order stacks. These systems form a robust hierarchy closely related to the Caucal hierarchy and higher-order recursion schemes. This latter connection demonstrates their importance as models for programs with higher-order functions.
We study the global model-checking problem for (higher-order) pushdown systems. In particular, we present a new algorithm for computing the winning regions of a parity game played over an order-1 pushdown system. We then show how to compute the winning regions of two-player reachability games over order-n pushdown systems. These algorithms extend the saturation methods of Bouajjani, Esparza and Maler for order-1 pushdown systems, and Bouajjani and Meyer for higher-order pushdown systems with a single control state. These techniques begin with an automaton recognising (higher-order) stacks, and iteratively add new transitions until the automaton becomes saturated.
The reachability result, presented at FoSSaCS 2007 and in the LMCS journal, is the main contribution of the thesis. We break the saturation paradigm by adding new states to the automaton during the iteration. We identify the fixed points required for termination by tracking the updates that are applied, rather than by observing the transition structure. We give a number of applications of this result to LTL model-checking, branching-time model-checking, non-emptiness of higher-order pushdown automata and Büchi games.
Our second major contribution is the first application of the saturation technique to parity games. We begin with a mu-calculus characterisation of the winning region. This formula alternates greatest and least fixed point operators over a kind of reachability formula. Hence, we can use a version of our reachability algorithm, and modifications of the Büchi techniques, to compute the required result. The main advantages of this approach compared to existing techniques due to Cachat, Serre and Vardi et al. are that it is direct and that it is not immediately exponential in the number of control states, although the worst-case complexity remains the same.