VictorJuiz/thesis huggingface dataset:
Mass-dependent behaviour and the starvation-predation risk trade-off in passerine birds

For any individual to survive and reproduce it needs to gain sufficient energy to avoid starvation and while doing so avoid being killed by a predator. For birds, the massdependent predation risk hypothesis predicts that, because increased mass is expected to reduce maximum flight performance when escaping from predators, the starvationpredation risk trade-off will be mass-dependent. This thesis carried out a series of five studies to test specific theoretical predictions of this general hypothesis. The first study used data on the blackbird Turdus merula to model, for the first time for any species, how mass changes diurnally and seasonally over the whole year. The results showed that both seasonal and diurnal mass change were regulated as predicted by mass-dependent predation risk. The next three experimental studies used specially designed automated weighing and identification systems to investigate how wild great tits Parus major deal with mass-dependent predation risk. Perceived predation risk was manipulating using model sparrowhawks and the results showed, for the first time, that birds are capable of changing their diurnal body mass gain strategy in response to heightened predation risk. Then the effect of diurnal mass gain on flight performance was examined, no significant effects could be shown but the experiment demonstrated that this result, and previous similar results, are due to insufficient sample size rather than the absence of an effect. The final experiment investigated the effect of capture, by humans, on the perception of risk. Birds increased mass in response to capture consistent with the event being perceived as an interruption to foraging that increased starvation risk. Finally, a study of the house sparrow Passer domesticus showed that they appear to be responding to mass-dependent predation risk in a way that makes them particularly vulnerable to any decrease in the predictability of their food supply. The results suggest that mass-dependent predation risk may be the mechanism that has driven recent dramatic house sparrow declines.

Advisor: Cresswell, W
Optimising mobility outcomes after severe ankle injury in adults

Severe ankle injuries can result in ligament rupture or a fracture. A major problem after such injuries is limitation in mobility. Weight bearing tasks, such as walking, become a problem because of pain, deficits in joint range of motion and muscle strength. This thesis studies a key dilemma in early rehabilitation, whether to immobilise the ankle or allow joint motion to improve mobility outcomes. Studies have focused on two scenarios, severe ligament rupture, and unstable fractures managed through open reduction and internal fixation (ORIF). The analysis of gait outcomes was an important component of this thesis and a novel analytical method was developed to normalise gait velocity in the estimation of speed-dependent gait outcomes.
A systematic review and meta-analysis was conducted including evidence to July 2014. The reporting and design of trials was universally poor. In the 6 weeks of recovery following ankle ORIF surgery, there was insufficient evidence that early ankle movements offered a benefit to mobility recovery compared with immobilisation in a cast. Ankle movements compared with immobilisation reduced the risk of venous thrombosis/thromboembolism. However, compared with cast immobilisation, the risk of deep and superficial surgical site infection and fixation-related complications were higher when ankle movements were permitted.
To investigate the role of ankle supports in rehabilitation of walking after ORIF, two randomised cross-over studies were completed. In healthy participants with non-pathological gait, a walker boot induced gait abnormalities when compared with Tubigrip (elasticated bandage). There were no important differences in gait between a stirrup brace and Tubigrip. In people who had undergone ankle ORIF 6 weeks previously, a walker boot and to a lesser extent a stirrup brace offered improvements in gait symmetry and lower pain scores when compared with Tubigrip. Finally, a secondary analysis of the Collaborative Ankle Support Trial cohort (n=584) was conducted, which concluded that, in comparison to Tubigrip, 10 days of cast immobilisation provided greater probability of recovery of a range of mobility outcomes 4 weeks following injury.
This thesis contributes evidence favouring a role for ankle immobilisation in improving mobility following severe ankle injury in adults. Clinicians should be aware of the benefits and risk of harms outlined, as well as the limitations in the current evidence base.

Keywords: ankle
orthopedic apparatus
sprains
gait disorders
fractures
Advisor: Lamb, S
Willett, K
Markov Functional Market Model nd Standard Market Model

The introduction of so called Market Models (BGM) in 1990s has developed the world of interest rate modelling into a fresh period. The obvious advantages of the market model have generated a vast amount of research on the market model and recently a new model, called Markov functional market model, has been developed and is becoming increasingly popular. To be clearer between them, the former is called standard market model in this paper. Both standard market models and Markov functional market models are practically popular and the aim here is to explain theoretically how each of them works in practice. Particularly, implementation of the standard market model has to rely on advanced numerical techniques since Monte Carlo simulation does not work well on path-dependent derivatives. This is where the strength of the Longstaff-Schwartz algorithm comes in. The successful application of the Longstaff-Schwartz algorithm with the standard market model, more or less, adds another weight to the fact that the Longstaff-Schwartz algorithm is extensively applied in practice.
Structural studies of integral membrane GPCR accessory proteins

GPCR accessory proteins regulate the strength, efficiency and specificity of signal transfer upon receptor activation. Due to the inherent difficulties of studying membrane proteins in vitro and in vivo, little is known about the structure and topology of these small accessory proteins. Two examples of GPCR accessory proteins are the Melanocortin-2 receptor accessory protein (MRAP) and the Receptor-activity-modifying protein (RAMP) family. MRAP and RAMP1 are the main focus of this thesis in which they are thoroughly characterised by solution-state NMR and further biophysical techniques.
The single-pass transmembrane domain protein MRAP regulates the class A GPCR melanocortin receptors. It is specifically required for trafficking the melanocortin-2-receptor from the endoplasmic reticulum to the cell surface and subsequent receptor activation. A remarkable characteristic of MRAP is its proposed native dual-topology, which leads to an antiparallel homodimeric conformation. Investigation of the biochemical and biophysical properties of MRAP revealed an α-helical transmembrane domain, and an α-helical N-terminal LD(Y/I)L-motif. Further efforts concentrated on establishing the homodimeric conformation of MRAP in vitro.
RAMP1 facilitates receptor trafficking and alters the ligand specificity of the GPCR Class B receptors calcitonin receptors and calcitonin receptor-like receptors. Moreover, RAMP1 is required to act as a Calcitonin-gene-related peptide (CGRP) receptor (RAMP1). RAMP1 has been shown to form stable parallel homodimers in the absence of its cognate receptor. Its dimerisation and the possible dimerisation motif PxxxxP-motif were studied extensively.
With the goal of understanding the mechanism of dimerisation and the role of GPCR accessory proteins I have used solution-state NMR in detergent micelles as my main technique. NMR provides unique possibilities for understanding the structure and dynamics of such small membrane proteins.

Keywords: NMR
RAMP
MRAP
structural biology
GPCR accessory proteins
membrane proteins
Advisor: Schnell, JR
Out-of-body and near-death experiences

What certainty is there for personal survival after death? Five key authors, critically analysed in this thesis, think that OB/ND experiences offer such assurances. Most OB/ND events follow severe clinical crises profoundly embarrassing cerebral function. At the nadir of brain function, invariably resulting in unconsciousness, authors aver that the escape of soul (Sabom), mind, or free consciousness (Moody, Ring, Grey, Fenwick), in providing glimpses of heaven, offers proof of immortality. I disagree.
The semantic content of early-phase ND experiences reveals dream-like bizarreness and illogicality, consistent with de-activation of critical cortical controls. Conversely, late-phase experiences, tinged with 'moral' compulsions about earthly responsibilities, herald the progressive intrusion of conscious-awareness into that subconscious mentation. These experiences, abruptly terminating as conscious-awareness erupts, are transient - as demonstrated by narrative word counts - indicating origins from reawakening, not moribund, brains. My argument is underpinned by these latter crucial observations. Pain, intruding into ND phenomenology, is another occurrence hardly consistent with an escape of mind or 'free consciousness' into the hereafter.
"Tunnel" phenomenology, a rapid movement from darkness into heavenly brightness, involves a retrospective synthesis of vestibular-generated rotation/accelerations, and a progressively enlarging and engulfing light, signalling re-establishment of an effective circulation to associative visual centres. The content of ND experiences, as with dreams, involves the temporo-parietal cortex.
OB experiences derive from central vestibular activity (superior and inferior parietal lobules) in dormant, recumbent patients. Allied aberrations of allocentric space create bodily reduplications and sensed invisible presences. Thus, OB do not warrant "mystical" interpretations.
The spiritual overtones accorded OB/ND experiences by authors are inconsistent with classical (Judaeo-Christian) accounts of divine disclosure. The eschatology adumbrated in published texts implies immortality, and seriously fails to embrace a preferred resurrectional eschatology as professed credally. I therefore conclude that OB/ND phenomenology, rather than offering alleged glimpses of eternity, reflects living, not dead, brains re-awakening to full conscious-awareness from antecedent metabolic insults.

Advisor: Brooke, J
Arginine methylation in the E2F1 pathway

The E2F1 pathway plays an important role in coordinating early cell cycle progression. Deregulation of the E2F1 pathway, which may be brought about by somatic mutations in genes such as INK4A, RB1 and CDK4, is found in a majority of cancers. The transcription factor E2F1 is able to activate genes involved in proliferation as well as apoptosis, but the mechanisms that govern these opposing biological effects remain poorly understood. In this study, I would describe how E2F1 activity can be regulated by two novel post-translational modifications which result in different functional consequences. It was found that PRMT1 asymmetrically methylates E2F1 at R109, while PRMT5 symmetrically methylates R111 and R113. The symmetric dimethyl marks on E2F1 promoted the recruitment of Skp2, a component of the E3 ubiquitin ligase complex, which coincided with decreased protein stability and transcriptional activity, as well as enhanced cell proliferation and reduced apoptosis. The asymmetric dimethyl marks on E2F1 was found to hinder symmetric dimethylation, leading to reduced cell proliferation and enhanced apoptosis. The competition between PRMT1 and PRMT5 at the E2F1 RG-rich motif was found to be regulated by the adjacent cyclin A binding site. Induction of DNA damage, which resulted in decreased cyclin A level, corresponded to an increase in PRMT1 and decrease in PRMT5 binding. This study uncovers a new mechanism in E2F1 regulation and establishes the importance of arginine methylation in cell proliferation and apoptosis.

Keywords: PRMT1
PRMT5
E2F1
Cancer
Methylation
Advisor: La Thangue, N
Ligand design and mechanism in hydroformylation

In this work the synthesis of new potentially trans-chelating biphosphine ligands is described and their value in rhodium catalysed hydroformylation evaluated. The reactions of biphosphine diolefin rhodium complexes with hydrogen in methanol, monitored by 1H- and 31P-NMR spectroscopy were used to determine trans-chelating ability. Complexes of 1,5-bis(diphenylphosphino)-3-oxapentane and 1,3-bis- (4-diphenylphosphinobenzyl)benzene formed rhodium dihydrides solely whereas the more flexible 1,7-bis(diphenylphosphino)-4-oxaheptane gave isomeric rhodium dihydrides and a solvate complex. The reaction of diolefin complexes with hydrogen and carbon monoxide in dichloromethane was also investigated. The 3-oxapentane ligand, readily synthesized from 3-oxapentane-1,5-diol, as its rhodium complex gave a n—/iso aldehyde ratio of 9:1 for 1-octene hydroformylation (100°, 80 psi, 1:1 hydrogen/carbon monoxide).
Secondly, reactive intermediates relevant to hydroformylation were identified using 13C- and 2H-labelling and 1H, 13C and 31P-NMR spectroscopy. Hydridocarbonylbis(triphenylphosphine)rhodium(I), the probable catalytic cycle initiator, was conclusively shown to be the initial product of hydridocarbonyltris(triphenylphosphine)rhodium(I) under hydroformylation conditions. The kinetics of interconversion of these latter two complexes were examined by saturation transfer 31P-NMR. On reaction of the dicarbonyl complex with styrene no alky1-rhodium complexes were observed, but an iso-acyl intermediate which isomerizes rapidly at ambient temperature was identified and a structure proposed. A similar n-acyl complex, from 1-octene, shows dynamic NMR behaviour explained in terms of triphenylphosphine isomerization at lower temperature and acyl-alkyl interconversion at high temperature.

Advisor: Brown, J
Role of HR23B, HDAC6 and Myd88 and their interplay in response to HDAC inhibitor treatment

Abnormal epigenetic control is a common early event in tumour progression, and aberrant acetylation in particular has been implicated in tumourigenesis. Histone deacetylases (HDACs) are enzymes that regulate acetylation of chromatin and a variety of other non-histone substrates. Significantly, HDAC inhibitors are potent anti-proliferative agents and exhibit clinical activity in lymphoproliferative and haematological maligancy. However, the mechanistic details by which HDAC inhibitors affect proliferation remain to be elucidated. I have explored the cellular processes affected by HDAC inhibitors, and begun to illuminate a new pathway, regulated by HDAC, which impinges on the cellular effect of HDAC inhibitors. My results suggest that the proteins HR23B and Myd88 are important sensitivity determinants for HDAC inhibitor treatment, and that their interplay with HDAC6 dictates cell fate choice between survival by autophagy or apoptosis.

Keywords: Myd88
HDAC6
biomarker
HDAC
HR23B
Advisor: La Thangue, N
Actuation of DNA cages and their potential biological applications

DNA cages are polyhedra self-assembled from synthetic oligonucleotides in a one-pot process. The main system described in this thesis is a reconfigurable, wire-framed DNA tetrahedron in nanometre-scale. On one of its vertices this tetrahedron has an overhang that can hybridise with a specific sequence of nucleic acids and open the cage.
We describe the design of a reconfigurable cage that remained closed under physiological conditions and only opened in the presence of an appropriate signal in solution. Fluorescence techniques were employed to distinguish the open and closed states of the cage.
We used flow cytometry and confocal microscopy to successfully established the open and closed states of the cage inside live cultured mammalian cells. Further experiments revealed that the DNA cage could be opened by a separately transfected signalling strand. Hybridisation between two separately transfected systems was possible. The DNA cage was then simplified to a DNA duplex so that the intracellular interactions between the two nucleic acids systems could be studied more efficiently. Microscopy images showed that the interaction occurred in membrane-bound compartments.
We describe an investigation into the use of various cellular RNAs, including full-length mRNA and tRNA-RNA fusion, to actuate the DNA cages. Choosing an appropriate cellular opening signal remains a challenge. Analysis showed that bulky cellular RNA experienced steric hindrance with the rigid DNA cage. Finally, other potential biological applications of DNA cages, such as using DNA nanostructures as the carriers for genetic therapeutic agents, were also presented.

Keywords: DNA cages
DNA nanotechnology
Advisor: Turberfield, A
Natural resource content of foreign trade and structural bias

The purpose of this study is to test the hypothesis that centrally- planned economies are characterized by what is called a bias towards absorption of natural resource intensive products (NRP) which is said to affect in turn the commodity structure of their foreign trade. While the study includes a detailed analysis of foreign trade structures and the absorption of NRP by final consumers, it is the intermediate demand for NRP and its determinants which are emphasized. Following the suggestions in the literature that the technologies used by the centrally- planned and market-type economies are different, the role of technology in determining intermediate demand for NRP has been examined in detail.
Bias is defined here in terms of inter-country differences and the present comparison involves a case-study of Czechoslovakia as a centrally-planned economy and Austria as a market-type economy based on an input-output model. The use of the input-output model in inter- national comparisons of production and use of commodities has been criticized on the following grounds: (1) The distinction between technology and substitution is ignored in the model. (2) International differences in relative prices are normally ignored or assumed away in empirical work. (3) The comparisons may be severely affected by imperfections of input-output tables. This study attempts to answer the above criticism in an original way. New methods of sensitivity analysis were designed to test for the existence of the 'triangular' and other 'fundamental' properties of the technological matrices. In addition, the assumption of temporal stability of input-output coefficients is relaxed and an attempt is made to distinguish between technology and substitution with the help of the RAS method. Further analysis of the impact of relative prices on input-output flows was derived from an analysis of indirect taxation.
The main conclusion of this study is that Czechoslovakia had a considerable NRP import bias which was primarily due to the pro-NRP absorption bias of final consumers. However, it is unlikely that 'excessive' aggregate demand for imports originated in 'NRP-biased' technology. This empirical analysis provides strong evidence that the production processes with regard to the use of NRP were highly similar in both countries.
Applications of the Heck reaction for the syntheses of substituted pyridines and β,β-disubstituted vinyl Weinreb amides: studies towards the syntheses of inthomycin B and inthomycin C

The Heck reaction has become a fundamental reaction for synthetic organic chemists over the last half century and is utilised heavily in the fine chemical industry and for natural product synthesis. This thesis describes some of the applications of the Heck reaction to modern day organic synthesis.
Introduction: This section presents an overview of the Heck reaction starting from its conception during the late 1960s to present day understanding. A variety of ligand classes are described along with commonly accepted catalytic cycles for their activity during the reaction.
Results and Discussion: In the first part of the thesis, the use of a cross-metathesis/Heck reaction protocol to synthesise a range of 2,4,6-trisubstituted pyridines is described. Attempts were made to expand the scope of the methodology by employing vinyl Weinreb amides, but this proved unsuccessful for the synthesis of pyridines. Nevertheless, the Heck reaction on vinyl Weinreb amides worked efficiently and the scope of this arylation was explored. Following on, the functionalisation of the Weinreb amide products was studied to generate a range of enone products, some of which would be difficult to synthesise via direct Heck reaction on the respective precursor enone.
In the second part of the thesis, previous syntheses of inthomycin B and inthomycin C are described. The synthesis of inthomycin B and inthomycin C were then attempted using an unprecedented Mukaiyama aldol/cross-metathesis based approach to generate the triene core of both natural products.

Keywords: Heck reaction
Pyridines
Advisor: Donohoe, T
Superconductors and high magnetic fields

This thesis describes a portfolio of work aimed at the high field applications of superconductors and can be split into four main topics:
The thermal stability of technical superconductors. This section investigates the effects of thermal perturbations on technical superconducting wire used in MRI scanner construction. The ultimate aim of this section is to predict how the architecture of the wire may affect its thermal stability. To this end a detailed finite element analysis model was constructed, verified by detailed experimental data, which could then be used to quickly and easily vary the wire’s parameters. Design of a high field pulsed electromagnetic coil for flux trapping in superconductors. This section details the design, construction and testing of a novel pulsed high field magnet. The design uses finite element analysis to predict the electromagnetic, thermal and structural properties of the coil.
Explosive testing of high tensile fibres used in the construction of the high field coil. This section describes the refinement and use of a novel method for testing the mechanical properties of high tensile fibres in cylindrical geometries by using highly pressurized copper vessels.
Pulsed field magnetization of bulk high temperature superconductors. This section discusses the process of magnetizing bulks of high temperature superconductors by using pulsed magnetic fields. It investigates how the trapped field varies with the magnitude and rise-time of the magnetizing field, sample temperature and time after magnetization.

Keywords: superconductors
thermal stability
pulsed magnetic fields
high tensile fibre
magnetic fields
magnet design
superconducting magnets
high magnetic fields
bulk superconductors
pulsed field magnetisation
flux trapping
Superconductivity
finite element analysis
Advisor: Jones, H