VictorJuiz/thesis huggingface dataset:
A crystallographic comparison of protein molecules with related conformations

The multiple isomorphous replacement method of protein crystallography has revealed the structures of several proteins, but the method is limited by the need for many isomorphous crystals. This difficulty could be eased to a large extent by using a molecular fragment as a model for the unknown structure, when only one set of X-ray intensities need be measured. This thesis discusses ways to determine the orientation of such a partial structure, and recommends a new method to determine the location of a properly oriented partial structure in the crystal unit cell.
These methods were applied to the proteins human lysozyme, hen lysozyme crystallised at a high temperature, and goat α-lactalbumin, for all of which part of the published structure of hen lysozyme was used as a model. Only the application to human lysozyme was successful, and the failure in the case of the high-temperature hen lysozyme is surprising. An application of these methods to the antibiotic thiostrepton, using an almost complete structure from another crystal form as a model was successful.
Having found a partial structure which explains the X-ray data moderately well, it is necessary to complete and refine the model. Several of the theories discussed in this thesis assume Wilson statistics, which are shown to apply to human lysozyme surprisingly well. Three types of completion / refinement technique were applied, a least squares refinement of atomic occupancies, direct methods, and the use of maps with Fourier coefficients with phases derived from the partial structure. The first two methods failed, but the third had partial success. The relationship between "difference maps", Sim weighting, and the α-synthesis is discussed; an extension of Luzzati's treatment of maps with Fourier coefficients F exp(iac) shows that of these three Fourier syntheses, the α-synthesis has the best (unknown peak height)/(known peak height) ratio, whereas Sim weighting has the best signal/noise ratio – which, incidentally, never exceeds unity for acentric data – where "noise" is defined in a more realistic way than that adopted by Sim. A corrected and extended version of a previous semi-quantitative account of difference maps is given.
The application of various Fourier syntheses to human lysozyme structure factor amplitudes proceeded as a test of methods in parallel with the isomorphous replacement study by other workers; it is recommended that both Fobs, and difference maps be calculated, using Sim weighting. Small differences in the main chain conformations of hen and human lysozymes can be determined, missing side chain atoms can often be placed, but rearrangements of the structure as determined by the isomorphous replacement study are not always seen on difference maps.
The value of the residual for a randomly wrong structure when a mixture of acentric and centric data is used is shown to be within 0.007 of the value which corresponds to a linear interpolation between the all centric and all acentric limiting cases.
Temporal orienting in the human brain: neural mechanisms of control and modulation

The main aim of the experiments reported in this thesis was to explore the neural mechanisms underlying the temporal orienting of attention. In Chapter 3, I explored the possible dissociation between exogenous and endogenous temporal orienting by comparing reaction times to targets appearing after rhythmic or symbolic cues. Behavioural results provided evidence for the existence of dissociable exogenous and endogenous types of temporal orienting of attention. The experiment in Chapter 4 combined spatiotemporal expectations using rhythmic moving cues to test the modulatory effect of exogenous temporal orienting in the brain. Specifically, I used EEG to test the effect of temporal orienting on perceptual and motor stages of target analysis, as well as on anticipatory oscillatory brain activity. The time-frequency analysis revealed that rhythmic cues can entrain slow brains oscillations, providing a putative mechanism for enhancing the perceptual processing of expected events. Spatiotemporal expectations also modulated the amplitude of visual responses and the timing and amount of preparatory motor activity. In Chapter 5, I used a novel task to explore the neural modulatory effects of spatial and temporal expectations acting in isolation or in coordination. For the first time, the analysis of early visual responses demonstrated that temporal expectations alone, independently of spatial orienting, can enhance early visual perceptual processes. The time-frequency analysis in this experiment showed a desynchronisation of alpha oscillations focused over central-parietal electrodes induced by rhythmic cues that were independent of spatial expectations. When rhythmic cues carried spatiotemporal information, the alpha desynchronisation also spread over contralateral occipital electrodes. In Chapter 6, fMRI was used to test the possible neural dissociation between motor and temporal orienting. The results confirmed the large overlap between these two processes, but also indicated independent behavioural and neural effects of temporal orienting. Temporal orienting activated the left IPS across motor conditions, further implicating the left IPS in temporal orienting. Based on the results of these experiments, directions for future studies are discussed.

Keywords: Temporal Expectations
neural oscillations
fMRI
Attention
EEG
Advisor: Nobre, A
Cycles in edge-coloured graphs and subgraphs of random graphs

This thesis will study a variety of problems in graph theory. Initially, the focus will be on finding minimal degree conditions which guarantee the existence of various subgraphs. These subgraphs will all be formed of cycles, and this area of work will fall broadly into two main categories.
First to be considered are cycles in edge-coloured graphs and, in particular, two questions of Li, Nikiforov and Schelp. It will be shown that a 2-edge-coloured graph with minimal degree at least 3n/4 either is isomorphic to the complete 4-partite graph with classes of order n/4, or contains monochromatic cycles of all lengths between 4 and n/2 (rounded up). This answers a conjecture of Li, Nikiforov and Schelp. Attention will then turn to the length of the longest monochromatic cycle in a 2-edge-coloured graph with minimal degree at least cn. In particular, a lower bound for this quantity will be proved which is asymptotically best possible.
The next chapter of the thesis then shows that a hamiltonian graph with minimal degree at least (5-sqrt7)n/6 contains a 2-factor with two components.
The thesis then concludes with a chapter about X_H, which is the number of copies of a graph H in the random graph G(n,p). In particular, it will be shown that, for a connected graph H, the value of X_H modulo k is approximately uniformly distributed, provided that k is not too large a function of n.

Keywords: edge-colouring
random graphs
Ramsey theory
Advisor: Scott, A
G-protein modulation of ionic currents in cardiac myocytes

The modulation of L-type calcium current (ICa) and the catecholamine-induced chloride current (ICl,cAMP) by G-protein coupled regulatory pathways were studied in isolated guinea pig cardiac ventricular myocytes using the whole cell patch clamp and flash photolysis techniques. A number of novel findings are reported in this thesis.
The rapid release of GTP, the natural ligand of G-proteins, from its inert caged precursor produced a large enhancement of ICa which could be detected within 20 ms of the photolysing light pulse. A fast component of this response persisted under conditions of current rundown and inhibition of cAMP-dependent phosphorylation. This suggests the involvement of a membrane-delimited pathway not dependent on soluble second messengers. The photorelease of the non-hydrolysable GTPγS caused a biphasic increase in ICa in the majority of myocytes and a sustained response in the others.
Pipette dialysis with GTPγS had a three-fold effect: pertussis toxin-sensitive inhibition of the ICa responses to isoprenaline, forskolin and photoreleased GTP; competitive inhibition of the enhancement of ICa by further photoreleased GTPγS; and modulation of the kinetics of cAMP-dependent activation of ICl,cAMP and ICa without any significant changes in their magnitudes.
The flash photolysis of caged cAMP produced large increases in both ICl,cAMP and ICa but the latter was more than twice as sensitive to cAMP (EC50 = ~ 1.1 μM and ~ 0.47 μM).
Urotensin has recently been identified as the ligand for a previously orphaned G-protein coupled receptor, and has been shown to be a potent chronic vasoconstrictor. This thesis reports an additional modulatory effect on ICl,cAMP. μM urotensin had no effect on its own but potentiated responses to sub-maximal sympathetic stimulation.
Estrogen reduces forskolin- and isoprenaline-stimulated cAMP accumulation in the rat heart and inhibits cardiac ICa via a G-protein. However, the application of μM ß-estradiol to guinea pig myocytes in the presence of low doses of either forskolin (0.5 μM) or isoprenaline (20 nM) produced large increases in ICl,cAMP. This effect was mediated by a cell surface receptor. The involvement of nitric oxide synthase (NOS) was not required, unlike in acute estrogenic responses in vascular endothelia. Raloxifene, a selective estrogen receptor modulator (SERM), was similarly able to potentiate the results of sympathetic stimulation but with a much slower time course.

Advisor: Powell, T
Searches with the ATLAS detector for new coloured particles in the Jets + Missing Energy channel in early LHC data

The switching on of the Large Hadron Collider (LHC) in March 2010 and its successful operation thereafter has opened doors in the search for new physics beyond the Standard Model. Supersymmetry (SUSY) is one of the leading theories that extends the Standard Model of particle physics. A search for new SUSY particles is presented requiring large numbers of hadronic jets and missing transverse momentum. Novel background estimation techniques were developed specifically for this final state, allowing the control of the backgrounds where the missing transverse momentum is dominated by jet miss-measurement. Other backgrounds are estimated from Monte-Carlo simulations validated and normalised in dedicated control regions. No significant excess was observed in the search. Model independent upper limits on the number of signal events passing the selection are given and the results are also interpreted in two planes of the parameter space. This is the most recent and sensitive incarnation of several searches developed by the author in this channel.

Keywords: Supersymmetry
LHC
SUSY
ATLAS
Physics
Particle Physics
Advisor: Barr, A
Hall algebras and Green rings

This thesis consists of two parts, both of which involve the study of algebraic structures constructed via the multiplication of modules.
In the first part we look at Hall algebras. We consider the Hall algebra of a cyclic quiver algebra with relations of length two and present a multiplication formula for the explicit calculation of products in this algebra. We then look at the case of a cyclic quiver with two vertices and describe the corresponding composition algebra as a quotient of the positive part of a quantised enveloping algebra of type Ã1
We then look at quotients of Hall algebras of self-injective algebras. We give an abstract result describing the quotient of such a Hall algebra by the ideal generated by isomorphism classes of projective modules, and also a more explicit result describing quotients of Hall algebras of group algebras for cyclic 2-groups and some related polynomial algebras.
The second part of the thesis deals with Green rings. We compare the Green rings of a group algebra and the corresponding Jennings algebra for certain p-groups. It is shown that these two Green rings are isomorphic in the case of a cyclic p-group. In the case of the Klein four group it is shown that the two Green rings are not isomorphic, but that there exist quotients of these rings which are isomorphic. It is conjectured that the corresponding quotients will also be isomorphic in the case of a dihedral 2-group. The properties of these quotients are studied, with the aim of producing evidence to support this conjecture. The work on Green rings also includes some results on the realisation of quotients of Green rings as group rings over ℤ.

Advisor: Erdmann, K
A study of some actions of growth-promoting peptides on skeletal cells

The binding of five 125I-labelled growth peptides (insulin, multiplication-stimulating activity (MSA), growth hormone (GH), epidermal growth factor (EGF) and platelet-deriyed growth factor (PDGF)) to chondrocytes isolated from rabbit and human cartilage, was examined.
Total binding of 125I-MSA and specific binding of 125I-insulin I-EGF to human fetal chondrocytes was shown between 13W and 22W gestational ages, but at 14W and 15W, 125I-PDGF did not bind specifically.
Specific binding of all five 125I-labelled peptides to post-natal rabbit (310g - 350g) chondrocytes was shown. For 125I-MSA, 125I-EGF and 125I-PDGF, specific binding increased with advancing age of the rabbit (from 233g - 397g) which was coincident with an increase in rabbit growth rate. For 125I-PDGF there was an increase in the number of binding sites/cell. Specific binding of 125I-insulin to chondrocytes from rabbits of 1095g was 37% less than from rabbits of 305g. The lower binding was accompanied by a decrease in the affinity constant and in the number of binding sites/cell and occurred at an age when rabbit growth rate begins to decrease.
Insulin (10 - 50μg/ml)increased 125I-MSA binding to human fetal and post-natal rabbit chondrocytes by 300% and 20% respectively and somatomedin C (1000ng/ml) increased 125I-PDGF binding to post-natal rabbit chondrocytes by 25%. Also, insulin at physiological levels (5 - 500ng/ml), increased the effect of plasma to stimulate [ 3H]-thymidine incorporation into post-natal rabbit chondrocytes by 54%, while insulin (5 - 500ng/ml), GH (1 - 5000ng/ml) and PDGF (10 - lOOng/ml) alone did not stimulate [3H]-thymidine incorporation. Growth peptides may therefore exert some of their growth-promoting actions in cooperation with each other and this may involve an increase in binding of one peptide by simultaneous binding of another.
Specific binding of 125I-insulin to human fetal chondrocytes in monolayer culture was also demonstrated but cell morphology was unstable and therefore binding measured may not have been truly representative of chondrocytes. It was concluded that the use of freshly isolated chondrocytes to measure growth peptide binding had more advantages.

Advisor: Ashton, I
Francis, M
(A) Structure and mobility studies of some layer compounds and (B) Electronic structure of molecules

Introduction
An atom or ion in a solid is associated with a given lattice site. Translational motion can however occur in solids and such diffusion processes can be studied by nuclear magnetic resonance, tracer diffusion and other methods. In ionic compounds the diffusion is also a mechanism for charge transport and hence there is an associated ionic conductivity.
[continued in text ...]
NOTE: The Abstract contains many indistinct letters in mathematical formulas and it is impracticable to reproduce it here.

Advisor: Dickens, P
Investigating the mechanisms responsible for DNA double-strand break-induced loss of heterozygosity in fission yeast

Loss of heterozygosity (LOH) is considered a causal event in the formation of many cancers, with increasing evidence suggesting that DNA double-strand breaks (DSBs) play a major role in its occurrence. Despite its prominence in cancer, however, the precise molecular mechanisms responsible for extensive LOH and how such events are suppressed in normal cells is poorly understood.
To investigate the mechanisms responsible for extensive break-induced LOH in eukaryotes, this study took advantage of an assay system in which such events could be identified through screening for loss of an auxotrophic his3+ marker, found ~25kb distal to an HO-endonuclease cut site in a non-essential minichromosome in Schizosaccharomyces pombe.
Studies using this system had previously shown that extensive break-induced LOH in wild-type background, whilst infrequent, was predominantly associated with large translocations resulting from both allelic crossovers during G2 phase and breakinduced replication (BIR). Such extensive loss of allele specific information was also found to require rhp55+, rhp51+, rhp54+ and mus81+. This study has identified an additional role for the MRN complex, Rad22 and RPA in such break-induced translocations, suggesting that both allelic crossovers and BIR require homologous recombination (HR) in fission yeast. Surprisingly, break-induced extensive LOH was still observed in HR mutants. In contrast to wild-type cells, however, such extensive LOH was found to arise predominantly through de novo telomere addition at, or near, the break-site. Interestingly, telomere addition was most frequently observed in a rad22Δ background that disrupts HR following end resection. Further analysis demonstrated that de novo telomere addition was also significantly increased in ku70Δ rhp55Δ cells. Moreover, overexpression of rhp51 in rhp55Δ cells led to a substantial reduction in break-induced de novo telomere addition. Together, these findings support a model in which HR prevents de novo telomere addition at DSBs by competing for resected ssDNA ends.
In addition to providing information on break-induced LOH this study has identified a requirement for the MRN complex in efficient repair in rhp55Δ cells, which was previously found to occur via sister chromatid recombination (SCR) or a HRdependent end-joining pathway (EJ). Interestingly, deletion of MRN components also resulted in an increase in telomere addition, providing further evidence that HR competes with telomere addition for the repair of DSBs.
Overall, these findings shed light on the competitive relationships between pathways of DSB repair/misrepair in S. pombe and how such mechanisms contribute to the prevention or promotion of genome instability.

Advisor: Humphrey, T
Efficient approaches to simulating individual-based cell population models

Computational modelling of populations of cells has been applied to further understanding in a range of biological fields, from cell sorting to tumour development. The ability to analyse the emergent population-level effects of variation at the cellular and subcellular level makes it a powerful approach. As more detailed models have been proposed, the demand for computational power has increased. While developments in microchip technology continue to increase the power of individual compute units available to the research community, the use of parallel computing offers an immediate increase in available computing power.
To make full use of parallel computing technology it is necessary to develop specialised algorithms. To that end, this thesis is concerned with the development, implementation and application of a novel parallel algorithm for the simulation of an off-lattice individual-based model of a population of cells.
We first use the Message Passing Interface to develop a parallel algorithm for the overlapping spheres model which we implement in the Chaste software library. We draw on approaches for parallelising molecular dynamics simulations to develop a spatial decomposition approach to dividing data between processors. By using functions designed for saving and loading the state of simulations, our implementation allows for the parallel simulation of all subcellular models implemented in Chaste, as well as cell-cell interactions that depend on any of the cell state variables. Our implementation allows for faithful replication of model cells that migrate between processors during a simulation. We validate our parallel implementation by comparing results with the extensively tested serial implementation in Chaste.
While the use of the Message Passing Interface means that our algorithm may be used on shared- and distributed-memory systems, we find that parallel performance is limited due to high communication costs. To address this we apply a series of optimisations that improve the scaling of our algorithm both in terms of compute time and memory consumption for given benchmark problems.
To demonstrate an example application of our work to a biological problem, we extend our algorithm to enable parallel simulation of the Subcellular Element Model (S.A. Sandersius and T.J. Newman. Phys. Biol., 5:015002, 2008). By considering subcellular biomechanical heterogeneity we study the impact of a stiffer nuclear region within cells on the initiation of buckling of a compressed epithelial layer. The optimised parallel algorithm decreases computation time for a single simulation in this study by an order of magnitude, reducing computation time from over a week to a single day.

Keywords: scientific computing
individual-based
agent-based
cell population
parallel
Advisor: James, O
Joe, P
Alexander, F
Definable henselian valuations and absolute Galois groups

This thesis investigates the connections between henselian valuations and absolute Galois groups. There are fundamental links between these: On one hand, the absolute Galois group of a field often encodes information about (henselian) valuations on that field. On the other, in many cases a henselian valuation imposes a certain structure on an absolute Galois group which makes it easier to study.
We are particularly interested in the question of when a field admits a non-trivial parameter-free definable henselian valuation. By a result of Prestel and Ziegler, this does not hold for every henselian valued field. However, improving a result by Koenigsmann, we show that there is a non-trivial parameter-free definable valuation on every henselian valued field. This allows us to give a range of conditions under which a henselian field does indeed admit a non-trivial parameter-free definable henselian valuation. Most of these conditions are in fact of a Galois-theoretic nature. Since the existence of a parameter-free definable henselian valuation on a field ensures that henselianity is elementary in calLring
, we also study henselianity as an calLring
-property.
Throughout the thesis, we discuss a number of applications of our results. These include fields elementarily characterized by their absolute Galois group, model complete henselian fields and henselian NIP fields of positive characteristic, as well as PAC and hilbertian fields.

Keywords: Valuations
Definability
Henselian
Model Theory of Fields
Absolute Galois Theory
Advisor: Koenigsmann, J
Kant, constructivism, and 'Kantian Constructivism'

In recent years a ‘constructivist’ interpretation of Kant’s views on the foundations of morality has become very popular. This thesis argues that Kant did not hold a constructivist view, and that constructivism is not in a broader sense ‘Kantian’ nor a sympathetic revision of Kant’s views. I begin by clarifying what makes a moral theory distinctively ‘constructivist’. Then I argue that the textual evidence does not support a constructivist reading of Kant, and explain some of the passages which suggest constructivism. Finally, I offer a critique of constructivism as a substantive meta-ethical view.

Keywords: Kant
Kantian constructivism
constructivism
meta-ethics
Advisor: Irwin, TH