VictorJuiz/thesis huggingface dataset:
The measurement of radical species of atmospheric importance
Keywords: spectroscopy
FM
radicals
NICE-OHMS
HO2

The measurement of radical species in the atmosphere has far reaching implications. For example, it is necessary to both understand and improve our knowledge of radicals in the atmosphere to better inform the models which in many cases are the best way of predicting future air quality and climate change. Although many of these models are often not fully representative of all the processes occurring, they are the current best estimate based on the knowledge available, and can be useful in informing and directing future policy. The numerous, varied and interlinked cycles in the atmosphere are complex and only by obtaining data on specific species can accurate concentrations be retrieved and fed back into the models to improve their accuracy.
This work is concerned with the development and application of an ultrasensitive absorption spectroscopy technique to the problem of detection of the peroxy radical, HO₂. Noise Immune Cavity Enhanced Optical Heterodyne Molecular Spectroscopy (NICE-OHMS) combines cavity enhancement techniques (in order to increase the path length) with frequency and wavelength modulation techniques (in order to reduce the noise).
Following a discussion of the current detection methods used by atmospheric scientists to accurately measure and quantitative concentrations, some preliminary work on the detection of ammonia by a simple cavity enhanced absorption setup is presented. Pressure broadening and shift results were obtained for a number of ammonia transitions in the near infrared region, broadened by He, Ne, Ar, Xe, O₂ and N₂.
The bulk of the work concentrates on the implementation of the NICE-OHMS technique, presenting the first results with the use of an external cavity diode laser and a ring shaped cavity. A sensitivity of 4 x 10⁻¹¹ cm⁻¹ Hz⁻1/2 is obtained on an individual rovibrational transition of methane at 6610.063 cm⁻¹, along with a selection of other data from the atmospherically important molecules methane, nitrogen dioxide and carbon dioxide, highlighting the broad wavelength range over which the instrument can operate. Finally, the NICE-OHMS technique is used to probe HO₂ radicals formed through the photolysis of a Cl₂/CH₃OH/O₂ mixture. Following the creation and detection of HO₂ radicals in the cavity, and based on the optimum sensitivity outlined above, a minimum concentration of 1 x 10⁹ molecules cm⁻³ has been demonstrated.
Analysis methods for single molecule fluorescence spectroscopy
Keywords: Time-Series Analysis
MVA
confocal
BVA
FRET
Photophysics
TIRF
SBVA
EBVA

This thesis describes signal analysis methods for single-molecule fluorescence data. The primary factor motivating method development is the need to distinguish single-molecule FRET fluctuations due to conformational dynamics from fluctuations due to distance-independent FRET changes.
Single-molecule Förster resonance energy transfer (FRET) promises a distinct advantage compared to alternative biochemical methods in its potential to relate biomolecular structure to function. Standard measurements assume that the mean transfer efficiency between two fluorescent probes, a donor and an acceptor, corresponds to the mean donor-acceptor distance, thus providing structural information. Accordingly, measurement analysis assumes that mean transfer efficiency fluctuations entail mean donor-acceptor distance fluctuations. Detecting such fluctuations is important in resolving molecular dynamics, as molecular function often necessitates structural changes. A problem arises, however, in that factors other than donor-acceptor distance changes may induce mean transfer efficiency fluctuations. We refer to these factors as distance-independent FRET changes.
We present analysis methods to detect distance-independent photophysical dynamics and to determine their correlation with distance-dependent FRET dynamics. First, we review a theory of photon statistics and show how we can use the theory to detect FRET fluctuations. Second, we extend the theory to alternating laser excitation (ALEx) measurements and demonstrate how fluorophore stoichiometry, a measure of fluorophore brightness, reports on distance-independent photophysical dynamics. Next, we provide a measure to determine the extent to which stoichiometry fluctuations account for FRET dynamics. Finally, we use a framework similar to the preceding along with recent advances in the theory of total internal reflection fluorescence (TIRF) microscopy FRET measurements to detect TIRF FRET fluctuations which occur on a timescale faster than the measurement temporal resolution. We validate our methods with simulations and demonstrate their utility in delineating RNA polymerase open complex conformational dynamics.
Transition metal catalyzed alkylation and synthesis of biotin derivatives
Keywords: catalysis synthesis alkylation biotin

Transition Metal Catalyzed Alkylation
We have reported methodology for the use of methanol as an alkylation reagent using catalytic rhodium or iridium species for the formation of branched products from methyl ketones. The synthetic utility of the dialkylated products was enhanced by performing a regioselective Baeyer-Villiger oxidation which allowed access to ester products. A range of different phosphine ligands were screened, and sterically hindered and electron rich phosphine ligands were found to favour the formation of enone and methoxy adducts under an O2 atmosphere. This interrupted hydrogen borrowing reaction enabled the in situ addition of a nucleophile to give more complex products. A range of tetrasubsitituted pyridines were then synthesized from 1, 5-dicarbonyl compounds formed in the methylenation/conjugate addition sequence. Finally, deuteration experiments suggest that the reaction proceeds via a monohydride mechanism, and the possibilities for the beneficial effect of O2 were discussed.
Synthesis of biotin derivatives
The streptavidin-biotin system was chosen for the studies of protein/ligand interactions at molecular level. A series of modified biotin ligands were designed and synthesized to introduce repulsive interations with streptavidin. The protein/ligand complexes were analyzed at high resolution by X-ray crystallography.
Characterising KMOS and scaling relations in the rich cluster MS0451.6-0305
Keywords: KMOS
infrared
cluster
MS0451
spectrograph
IFU

This Thesis contains two parts. Part I details my work on KMOS, a new instrument for the VLT and Part II details my research on scaling relations for the massive galaxy cluster MS0451.6-0305.
Part I: The K-Band Multi-Object Spectrograph (KMOS) is a new near infra-red (NIR) instru- ment to be installed at the Very Large Telescope (VLT). KMOS is capable of spatially resolved kinematics via 24 deployable integral field units (IFUs), each with a 2.8′′ field of view. I describe my contribution to the construction and optical characterisation of the spectrograph modules and instrument as a whole.
Part II: GMOS-N spectroscopy has been used to obtain velocity dispersions (σ) and archival HST photometry has been used to determine the effective radii (Re) & average surface brightnesses within Re (⟨I⟩e) of 26 confirmed cluster members of MS0451.6-0305 at z = 0.55. The Kormendy Relation, Faber-Jackson Relation and Fundamental Plane have been produced for the cluster and have been compared to the results for a local reference sample in Coma. GMOS-N g′ and r′ band photometry has also been used to produce a Colour-Magnitude Relation for MS0451.6-0305.
It is found that the KR and FJR disagree at the 2.1σ level with respect to luminosity evolution since z = 0.55. When correcting for size-evolution (SE), the magnitude offsets agree and are consistent with passive evolution of the galaxy stellar populations from a single burst of star formation 9.8+4.5-1.7 Gyrs ago or z = 1.7+∞-0.6. The median offset in the FP relation for the SE corrected data is also consistent with this formation epoch. Evidence is found for the evolution of the FP tilt in MS0451.6-0305, where it is shown to be steeper than that of the Coma FP, when expressed as a relation between galaxy mass and M/L.
N-heterocyclic carbene stabilisation of low valent metal centres for the activation of E-H bonds
Keywords: metal hydride
gold
iridium
bond activation
N-heterocyclic carbene
dehydrogenation

This thesis examines the effects of coordinating highly sterically demanding and strongly electron donating saturated N-heterocyclic carbenes (NHCs) at late transition metal centres.
Chapter III details the synthesis of a range of iridium complexes of the type (NHC)2IrHxCly [x = 1, 2; y = 0, 1], bearing the saturated NHCs 5-Mes, 6-Mes and 7-Mes. Unusually facile activation chemistry is observed in the reaction of [Ir(COE)2Cl]2 with 6-Mes and 7-Mes to form the doubly cyclometallated species (6-Mes')2IrH and (7-Mes')2IrH, which were fully characterised. The responses of these complexes to the addition of dihydrogen and HCl were studied, leading to the controlled synthesis of range of precursors to 14-electron iridium cations.
In Chapter IV the formation of low valent iridium cations with weakly coordinating anions is targeted. Isolation of the cationic complexes [(NHC)(NHC')IrH][BArf4] and [(NHC)2IrH2][BArf4] (NHC = 6-Mes, 7-Mes) showcases the stabilising power offered by these expanded ring systems. This allowed the study the interaction of these low valent species with a range of amine-borane substrates which are known to be readily dehydrogenated. Thermodynamic data on the C-H bond activation processes occurring at these iridium centres were able to be obtained due to facile, reversible oxidative addition of C-H bonds across the 14-electron iridium.
Chapter V focuses on the effects of increasing the steric bulk of these NHCs to limit the coordination of multiple ligands at the metal centre. Use of 2,6-diisopropyl-phenyl (Dipp) groups on the expanded ring NHCs, instead of mesityl groups, leads to an unprecedented mode of reactivity with [Ir(COE)2Cl]2. Activation and cleavage of C-N bonds in the carbene ring is observed, resulting in an open chain ligand chelating to the metal centre. Activation of the backbone in this manner has allowed the synthesis of saturated NHCs bearing a weakly coordinating anion on the ring. Here the first example of an anionic, saturated NHC is reported.
In Chapter VI these highly sterically demanding NHCs are exploited to stabilise active species in low valent gold chemistry. The extreme steric bulk of the 6-Dipp ligand disfavours reduction of Au(I) to Au(0), however the resulting cation is observed to interact strongly with the weakly coordinating anion, [BArf4]-. Thus, attempts were made to optimise the anion and conditions to isolate a catalytically relevant intermediate. The strong donating power of these expanded ring NHCs is also exploited to activate gold hydride complexes of the type (NHC)AuH (NHC = 6-Dipp, 7-Dipp). Analogues of [H3]+ containing gold atoms ([{LAu}2H]+ and [LAuH2]+) supported by expanded ring NHCs were also targeted.
Investigating the roles of zinc finger homeobox 3 in circadian rhythms
Keywords: Mutagenesis
Zfhx3
ENU
Behaviour
Circadian
Genetics
Mouse
Molecular

This thesis describes a program of investigation carried out by the author at MRC Harwell that shows, for the first time, that the gene Zfhx3 plays a role in modulating the circadian clock. The work has used the short circuit (Sci) mouse model to assess the molecular and genetic role of Zfhx3 in circadian behaviour and visual processing.
The Sci mutant was identified in an ENU mutagenesis dominant screen at MRC Harwell. The causative mutation was found in a highly conserved region of zinc finger homeobox 3 (Zfhx3), previously not known to play a role in the function of the circadian clock.
This study has shown that Zfhx3 RNA is specifically expressed in the adult SCN. Additionally, co-immunoprecipitation has shown that ZFHX3 can interact with core clock proteins, CRY1, CRY2 and PER2 and the Sci mutation causes differential effects on the RNA expression of Cry1, Cry2 and Per1. Genetic interaction experiments identified an interaction between Sci and Cry2 under constant darkness and a potential interaction between Sci and Cry1 and Cry2 under constant light. Together, these data indicate that Zfhx3 has a role in modulating the core circadian oscillator, in particular through cryptochromes.
A role for Zfhx3 has also been identified in visual processing and retinal function. Zfhx3 RNA was shown to be highly expressed in the ganglion, inner and outer nuclear layers of the retina. Sci mutants have increased retinal sensitivity by 20 fold, which may be attributed to a decrease in GABA neurotransmission in the retina.
From this study, novel functions for Zfhx3 within the circadian and visual systems have been identified. This exemplifies that molecular components of the circadian oscillator may remain to be identified and forward genetic approaches are facilitating advancements in this field.
Transcranial direct current stimulation (tDCS) as an adjunct intervention in stroke rehabilitation
Keywords: rehabilitation
stroke
tDCS
brain stimulation

Stroke is the leading cause of physical disability worldwide and patients are often left with substantial impairments in motor function. Intensive physiotherapy is the most widely used rehabilitative intervention following a stroke, but the potential for motor recovery with physiotherapy alone is limited by the activity of the residual cortex. Consequently there is increasing interest in combining traditional rehabilitation techniques with adjunct interventions to improve outcomes. Transcranial direct current stimulation (tDCS) is a promising tool for rehabilitation. Anodal stimulation of primary motor cortex increases cortical excitability and in stroke patients this translates into transient behavioural improvements after a single session of stimulation. This thesis aimed to investigate whether repeated sessions of tDCS delivered in conjunction with an intensive motor training program would result in long-lasting improvement of motor abilities in chronic stroke patients.
Twenty-four patients received motor training for two weeks for the paretic upper limb; patients were randomised to receive anodal or sham tDCS and were then examined over the subsequent three months to investigate behavioural improvements. All patients experienced a significant improvement in motor function following the motor training intervention. Patients who had received anodal tDCS experienced additional behavioural improvements that were more enduring over time. Baseline characteristics such as the presence of motor evoked potentials in the paretic hand and lesion volume were found to be significantly associated with initial motor impairment, and the degree of initial impairment and allocation to the anodal tDCS condition was found to predict therapy-mediated improvements in motor function.
The results presented in this thesis provide important information regarding the improvement in motor abilities associated with repeated sessions of tDCS, and in particular they suggest that tDCS may be utilised as a clinically useful tool for motor rehabilitation in chronic stroke. Furthermore, they suggest that baseline characteristics could be used to target interventions to patients most likely to benefit.
Viable project or wishful thinking? The European Union (EU) policy in the fight against terrorism: quest for strong human rights safeguards and enhanced security
Keywords: human rights
EU
terrorism

This thesis examines whether and how the EU counter-terrorism (CT) policy reconciles the demands of security with adequate protection of human rights. It starts from the assumption that human rights and security are mutually reinforcing and interdependent objectives in the CT fight where the erosion of one objective leads automatically to negative consequences in respect of the other objective. It specifically argues that the reconciliation of these two objectives has to be addressed at two distinct levels: first, in the framework of the EU primary law and, second, in the content of each EU CT provision. Consequently, the thesis examines both levels in order to respond to the research question. In the course of this investigation, the research has demonstrated that the legal framework resulting from the Treaty of Lisbon provides a basis for better addressing the human rights protection and security objectives of the EU CT policy. However, the analysis of three specific instruments – two in force and one at the level of a legislative proposal – provided contrasting results regarding the simultaneous fulfilment of the two imperatives outlined above. Moving beyond questions pertaining to the advancement of preventive criminal law and the possible reinforcement of a surveillance society, the thesis advances the hypothesis that, in the field, we are confronted more and more with what we could term ‘grey laws’ – following Dyzenhaus, Lynch and Reilly – due to their frailties as regards the tests of proportionality and legal certainty. Moreover, the thesis explores the EU’s stance as an actor in the field and the applicability of Wallace’s ‘pendulum model’ for CT decision-making, as well as the position of an individual subject to all the three measures indicated above. Solutions in order to overcome the identified shortcomings as well as further potential areas of research are also explored.
The characterisation of intestinal dendritic cells and the control of immune responses towards the microbiota
Keywords: immunology
intestine
pathology

Dendritic cells (DCs) are regulators of the immune response and are thought to be critical in maintaining tolerance towards the intestinal microbiota. Recent data have identified distinct subsets of DCs with specific functional properties. The objective of this thesis was to further define CD103⁺ and CX3CR1⁺ DCs in the intestine and to determine how DCs and regulatory T (Treg) cell responses are influenced by the microbiota.
Using multicolour flow cytometry, we identified two CD103⁺ DC subsets with differential aldehyde dehydgrogenase (ALDH) activity and two populations of CX3CR1⁺ cells. In the mesenteric lymph node CD103⁺ALDH⁺ DCs were highly mature (CD86hi, MHCIIhi), likely migratory (CCR7⁺) and enhanced Treg cell induction compared with ALDH⁻ DCs. CX3CR1int cells accumulated during bacterially-induced colitis suggesting a pro-inflammatory role whereas CX3CR1hi cells were associated with the production of the anti-inflammatory cytokine IL-10 during homeostasis.
We also assessed the generation of CD103⁺ DCs from bone marrow progenitors. Although only small proportions of CD103⁺ DCs were detected in culture with FLT3L or GM-CSF alone, the combination of FLT3L and GM-CSF induced CD103⁺ DCs with a phenotype similar to those found in the small intestine. Using this system we showed that TLR ligands and retinoic acid induce ALDH enzyme activity in vitro.
In order to assess how DCs and Treg cells respond to changes in the microbiota we employed broad-spectrum antibiotic treatment to deplete endogenous bacteria and also analyzed the impact of colonization with the model organism Helicobacter hepaticus. Interestingly, we did not detect alterations in the proportions of different DC subsets following antibiotic treatment or H. hepaticus infection. However, using a novel FoxP3huCD2-IL-10GFP reporter mouse, we found that IL-10 production by Treg cells was ablated following antibiotic treatment and significantly elevated following H. hepaticus infection. Preliminary investigation of the mechanism underlying this effect suggests a role for IL-27. In summary, this thesis provides further detail on the phenotype of intestinal DCs and shows that Treg cell IL-10 production is sensitive to the composition of the microbiota.
Population genetics genealogies under selection
Keywords: selection-mutation balance
strong selection
strong mutation
additive selection

In the presence of selection and mutation, the genealogy of a given sample configuration can be described by two classes of ancestral processes, namely the coalescent-in-a-random-background model of Kaplan et al. (1988) and the dual process with typed lines of Etheridge and Griffiths (2009). These two processes are based on the same forwards population genetics model. However, in the former model, selection is reflected in the ancestral frequencies in the population, while in the latter model, there are branching events that generate virtual ancestral lines. We simulate the dual processes with typed lines and derive the limits of the two ancestral processes under strong selection and under selection-mutation balance to address the question of to what extent the genealogy is distorted. The two ancestral processes generate the same limiting genealogy. In a two-allele population under strong selection, the disfavoured individuals in the sample are instantaneously converted to a random number of favoured individuals, and the limiting genealogy is governed by the usual Kingman’s coalescent. Under selection-mutation balance, all disfavoured individuals in the sample are instantaneously converted to the favoured type, and the limiting genealogy is determined by a time-changed Kingman’s coalescent. The proofs of these limiting processes are based on the convergence result of Mohle (1998, Lemma 1). The studies of selection-mutation balance are then extended to an additive selection model, where each individual is composed of L diallelic loci. In the corresponding dual process with typed lines, the evolution of the virtual lines on a faster timescale can be approximated by a deterministic process, while the evolution of the real lines is independent of the virtual lines. The structure in the limiting genealogy collapses to Kingman’s coalescent. We also let L tend to infinity, and obtain a full description of the limiting genealogy in the background selection model.
Explaining inter-state variation in aid for children at private religious schools in the United States, up to 2012
Keywords: US politics
Religion and politics
Education
QCA

This American Political Development research explains cross-state variation in aid for children at private religious schools in the United States up to the end of 2012. Using a mixed-methods approach I examine how the institutional orderings of Federalism, Constitution, Church and Party affect policymaker decisions to instigate and sustain programmes of aid. By ‘aid’ I mean education vouchers and tax credits, transportation, textbook loans, equipment, nursing and food services, and tax exemptions for private religious school property. I conduct Fuzzy-Set Qualitative Comparative Analysis across all fifty states, supported by interview and archival research in six case-study states – California, Florida, Illinois, Louisiana, New York and Utah – and by statistical treatment of the constitutional amendments known as ‘No-Aid Provisions’. All of the aid policies examined here are ‘submerged’ in Mettler’s terms, in that they help private organizations to take on state functions, re-frame such functions in terms of the marketplace, and are poorly understood by the public. In this thesis I extend Mettler’s conception of submergedness to explain when institutions matter, which institutions matter, and why they matter for religious school student aid. State decentralization is necessary for high levels of aid and a high proportion of Catholics is sufficient for high levels of aid. Republican control of the state offices is a necessary condition for the passage of tax credit or voucher scholarships but not for other types of aid. No-Aid Provisions are unrelated to aid. Of the four institutional explanatory conditions, Federalism and Church have the most important effects on aid for children at private religious schools. Party explains some types of aid but not all, and Constitution is surprisingly lacking in explanatory power.