This thesis investigates the implications of relaxing assumptions inherent in techniques that analyse solar wind transients observed by NASA's Solar TErrestrial RElations Observatory (STEREO). In the first research chapter, I relaxed the assumption that the STEREO spacecraft are stationary while observing a transient. For much of the parameter space investigated, this effect was minimal, however in some cases it resulted in differences in derived radial speeds of hundreds of km s-1, leading to large errors. Using real data examples, the difference this effect makes was shown. The second research chapter applies the previous analysis to Corotating Interactions Region (CIR) observations. CIR events were identifed in STEREO HI J-maps, analysed, and their predicted arrival times calculated at each of the STEREO and Advanced Composition Explorer (ACE) spacecraft. A superposed epoch analysis was conducted using the predicted arrival times as the zero epoch time. It was found that when the fixed STEREO spacecraft assumption was relaxed, the CIR related transients that I observed had their estimated propagation speed increase such that they were propagating at (or close to) the slow solar wind speed, a physically realistic change. Changes in the structure of a stream interface over 1-2 days were seen, calling into question some of the underlying assumptions, which assume constant propagation characteristics over longer time-scales. Finally, I consider acceleration of solar wind transients close to the Sun. I use the analysis from previous chapters to perform fits to transient trajectories close to the Sun and infers the size of the acceleration region required to achieve convincing fits at low elongation values. It was found that the behaviour of the transients is consistent with an acceleration region within which the transient accelerates and then adopts a constant propagation speed. The acceleration region does not appear to occur at a fixed radial distance, but rather is different for each event analysed.

A novel small field of view medical gamma camera - the Compact Gamma Camera (CGC) - has been developed at the University of Leicester to provide portable, high-resolution gamma imaging for applications in nuclear medical imaging. The suitability of this camera for medical imaging is investigated through Monte Carlo simulation, phantom studies and preliminary clinical testing. Quality assurance protocols are adapted for use with small field of view gamma cameras. These protocols are then used to provide a full characterisation of the CGC. The CGC is found to compare favourably to other small field of view systems in development. Phantom studies are described which show that the CGC is well suited to intraoperative imaging, particularly for use in sentinel lymph node biopsy. A Monte Carlo model is described that is designed to simulate the response of a pinholecollimated, scintillator-based gamma camera. The model is shown to accurately model sensitivity and spatial resolution. Previously derived analytical models are shown to be unsuitable for modelling finite source profiles and a new analytical model is described which addresses this shortcoming. This model is used to define appropriate test source sizes for the characterisation of small field of view systems. A modified version of the CGC - the Hybrid Compact Gamma Camera (HCGC) - is described which includes an optical imager in a coaligned configuration. The HCGC allows for functional and anatomical images to be obtained simultaneously. The use of hybrid optical-gamma imaging is novel in small field of view cameras and offers new possibilities for assisting surgeons in localising the site of uptake in procedures such as sentinel node detection.

The AAA (ATPase involved in various cellular activities) protein p97 is a versatile chaperone in the UPS (ubiquitin-proteasome system). As such, it is involved in many cellular pathways, for example membrane fusion, NF-κB activation, and DNA-damage repair. In these pathways, p97 engages an array of adaptor proteins to allow it to bind ubiquitylated substrates, process them and pass them to the proteasome for degradation. p97 forms a series of dedicated complexes that allow it to perform such a large number of tasks. The largest family of p97 adaptor proteins is the UBX (ubiquitin regulatory X) protein family, which includes p47 and FAF1 (Fas-associated factor 1). This thesis aims to probe the structures and biochemical properties of p97-UBX protein complexes to better understand how they help regulate p97 function. Recent advances in single-particle cryo-EM data processing of heterogeneous p97 datasets were utilised to improve the resolution of the cryo-EM model of p97-p47 in the presence of ADP. The method successfully removed unbound p97 and yielded a model of improved resolution. The main focus of the project was on FAF1. It was found to have a propensity to oligomerise via its coiled-coil domain, and bind p97 with a stoichiometry of 3:6. FAF1 decreased p97 ATPase activity, which may also be linked to its oligomerisation. A cryo-EM reconstruction of p97-FAF1 was obtained. It showed that p97 adopted a similar conformation to that seen in p97-UN. These data led to a proposed mechanism for how p97-FAF1 may be regulated. Furthermore, this data showed that p97- FAF1, p97-p47, and potentially other UBX proteins, share a trimer-hexamer binding mode. These common features impact the way they accomplish their tasks, indicating that p97 may utilise them by a common mechanism.

More accurate metabolic networks of pathogens and parasites are required to support the identification of important enzymes or transporters that could be potential targets for new drugs. The overall aim of this thesis is to contribute towards a new level of quality for metabolic network reconstruction, through the application of several different approaches. After building a draft metabolic network using an automated method, a large amount of manual curation effort is still necessary before an accurate model can be reached. PathwayBooster, a standalone software package, which I developed in Python, supports the first steps of model curation, providing easy access to enzymatic function information and a visual pathway display to enable the rapid identification of inaccuracies in the model. A major current problem in model refinement is the identification of genes encoding enzymes which are believed to be present but cannot be found using standard methods. Current searches for enzymes are mainly based on strong sequence similarity to proteins of known function, although in some cases it may be appropriate to consider more distant relatives as candidates for filling these pathway holes. With this objective in mind, a protocol was devised to search a proteome for superfamily relatives of a given enzymatic function, returning candidate enzymes to perform this function. Another, related approach tackles the problem of misannotation errors in public gene databases and their influence on metabolic models through the propagation of erroneous annotations. I show that the topological properties of metabolic networks contains useful information about annotation quality and can therefore play a role in methods for gene function assignment. An evolutionary perspective into functional changes within homologous domains opens up the possibility of integrating information from multiple genomes to support the reconstruction of metabolic models. I have therefore developed a methodology to predict functional change within a gene superfamily phylogeny.

No description available.

No description available.

No description available.

Kyoto University (京都大学) / 0048 / 新制・課程博士 / 博士(工学) / 甲第13035号 / 工博第2777号 / 新制||工||1404(附属図書館) / UT51-2007-H308 / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 内山 巖雄, 教授 森澤 眞輔, 教授 伊藤 禎彦 / 学位規則第4条第1項該当

The more we discover about the molecular composition of the interstellar medium (ISM) the more we realise how difficult it is to reproduce the mechanisms behind this complex chemistry. To date, over 175 different molecular species have been detected in the ISM. Many of them are formed in the gas phase, but there is a growing number of species that form more efficiently on grain surfaces during the collapse of star-forming cores. An important issue in mimicking the interstellar medium chemistry is that there are few observational clues about the synthesis of complex organic molecules on grains; experimental work coupled with chemical modelling is therefore essential in order to understand the chemical complexity of the ISM. UCL_CHEM is a computer model that takes into account the gas-grain interactions occurring during this collapse, with the aim of reproducing the observed abundances of molecules in various astronomical environments. The work in this thesis deals with the coupling of UCL_CHEM with the most recent experimental results on the formation in the solid state of various complex organic molecules including methyl formate (see Chapter 3) and ethylene oxide and acetaldehyde (whose chemistry is extensively discussed in Chapters 4 and 5), all which have been the subject of recent astronomical interest. Moreover, important revisions of some reactions occurring in the gas phase have also been made. Despite everything seeming straightforward concerning the interstellar chemistry in the gas phase, there is still a great deal to unearth in this regard. Oxygen, for instance, is an important player in the ISM because it is the most abundant element after hydrogen and helium. Although its chemistry seems well understood, we propose a revised scheme for its reactions with small unsaturated hydrocarbons (see Chapter 6) and we show how the new reaction network affects the molecular abundances of these linear carbon chains. In Chapter 6, we also emphasise the relevance in treating structural isomers as two different species when they show peculiar chemical behaviours. Another key issue in reproducing the interstellar molecular variety concerns the freezeout of species onto dust grain surfaces. In particular, we know little about the constituents of the icy mantles. In Chapter 7, we analyse the case of sulfur-bearing species because the most dominant ice component is still debated.

This work studies proton-proton collision data recorded by the ATLAS detector at the LHC from 2010 to 2012. The bulk of the work concerns measurements of the sum of the transverse energy of particles as a function of their pseudorapidity, η, at a centre-of-mass energy √s = 7 TeV. These measurements are performed using the entire acceptance of the ATLAS detector, 0 < |η| < 4.8, and are split into two classes of event: one requiring the presence of low transverse momentum particles and the other requiring particles with a significant transverse momentum. In the latter case measurements are made in the region transverse in φ to the hard scatter. As such, both measurements are sensitive to non-perturbative QCD processes. Comparisons are made with the predictions from various Monte Carlo event generators, which generally underestimate the quantity of transverse energy at high η. This discrepancy is found to be dependent on the choice of Parton Distribution Function. A new technique for performing model independent missing transverse energy searches is presented. The ratio of the branching fractions between Z → νν and Z → μ+μ− processes is used, with deviation from the Standard Model prediction inferred as an indication of new physics. Preliminary Monte Carlo results are shown by way of proof-of-principle. In addition, technical measurements of the muon reconstruction efficiency of the ATLAS inner detector trigger algorithms are presented. An established technique is used to obtain unbiased results, and the performance of the algorithms discussed.