Search

Alopecurus myosuroides, a problematic weed of UK winter cereals, is predominantly controlled by post-emergent herbicides with ALS and ACCase modes of action (MOA). Evolved resistance to these MOA - endowed by the mechanisms of targetsite (TSR) and/or enhanced metabolism (EMR) – threatens the sustainable production of winter cereals in the UK. This project aims to establish the frequency of ALS and ACCase resistance in UK populations of A. myosuroides and the factors that drive its evolution. From a 2011 survey of 92 UK A. myosuroides populations, mesosulfuron-methyl + iodosulfuron-methyl-sodium (ALS) resistance was confirmed in 81 populations; all 92 populations exhibited clodinofop-propargyl (ACCase) resistance. To understand how management affects resistance evolution, seventeen populations from the 2011 survey were resampled (2012–2014) so that estimated frequencies of phenotypic resistance, TSR and EMR could be compared to weed management histories. Fields in which spring crops were more frequently planted possessed A. myosuroides that exhibited lower levels of phenotypic resistance to both ALS and ACCase MOA. A simulation model was developed to describe A. myosuroides herbicide resistance evolution. However, this model could not be validated when parameterized with resistance and management data collected from the UK. In the 2011 survey, homozygous Pro-197-Thr ALS TSR mutations were absent. Phenotyping, germination, and genotyping experiments of plants from controlled heterozygous Pro-197-Thr crosses confirmed that there is a lethality associated with homozygous Pro-197-Thr mutations. To test the hypothesis that preexisting ACCase EMR increases the rate of ALS EMR selection, four A. myosuroides populations – three with ACCase EMR and one without - were selected over two generations with ALS herbicide. From dose-response analyses of survival, the three populations with ACCase EMR exhibited significant increases in ED50 values after selection, whereas the population without ACCase EMR did not.

My thesis presents a constructivist institutionalist analysis of the British ‘post-2008 context’, a conjuncture that I operationalise as the five-year period following the financial crash of 2007-2008. I conceptualise economic crisis as the perception of the need for ‘decisive intervention’ in response to economic policy failure. This constructivist conceptualisation asserts that the trajectory of political-economic restructuring in response to crisis is shaped by the way that policymakers ‘diagnose’ economic symptoms, and the success with which they persuade the electorate of the necessity of corresponding decisive interventions. Interpreting the trajectory of political-economic restructuring in the post-2008 context in this light, I operationalise and empirically interrogate the ‘crisis diagnoses’ and ‘crisis narratives’ of the two post-2008 governments. My empirical analysis is informed by, and speaks to, two principal literatures. The first concerns neoliberalism and ‘neoliberalisation’. The second analyses the emergence and subsequent failure of a fragile and contradictory ‘growth model’ in Britain, viewing this as an unanticipated consequence of neoliberal political-economic restructuring. My analysis indicates a more complex and contested process of crisis construction than the predominant focus on macroeconomic policy leads us to believe. I present evidence for the existence of two crisis diagnoses existing simultaneously in government – one neoliberal, one not – on the part of macroeconomic and industrial policymakers respectively. I argue that this reflects the impact of departmental boundaries on the process of crisis diagnosis. I find the neoliberal crisis diagnosis and the decisive interventions to which it points to be the predominant one, reflected in the constrained resources given over to post-2008 industrial policy and the centrality of the defence of neoliberalisation in post-2008 crisis narratives. Yet I argue that, in light of the latter literature, my findings point to the potential for contingency and categorical political-economic change in the present conjuncture.

Treatments for ischaemic stroke are limited and have low efficacy despite many years of promising research uncovering many potential therapeutic targets. As a result, stroke ranks as the third leading cause of death and the leading cause of disability worldwide. Mast cells have been identified as contributors to ischaemic stroke pathology, and are therefore a novel candidate for targeted stroke therapy. Indeed, genetic mast cell deficiency prior to onset of transient middle cerebral artery occlusion (tMCAo) in rats resulted in a significant reduction in blood brain barrier (BBB) permeability, oedema and neutrophil recruitment. Therefore the hypothesis of this thesis was that mast cells are active in the acute phase of experimental focal cerebral ischaemia, and interact with the brain to potentiate ischaemic pathology by release of a plethora of pro-inflammatory, vasoactive and proteolytic mediators. These mediators could degrade the BBB leading to vasogenic oedema, and may also prom ote an inflammatory milieu within the brain. Using wild type C57BL6/J (WT) and, mast cell deficient, C57BL6/J Kit w-sh/w-sh (Kit) mice in the tMCAo model of focal cerebral ischaemia, we found a significant reduction of BBB permeability, oedema and neutrophil recruitment. Additionally, sodium cromoglycate (SCG) treatment prior to tMCAo had the added effect of reducing lesion volume in WT mice. Seventy two hours post-tMCAo, genetic mast cell deficiency did not result in reduction of any of the parameters analysed. Investigation of protein expression in brain homogenates, twenty minutes and forty-five minutes post-tMCAo, indicated that tumour necrosis factor-alpha (TNF-α) was not responsible for the pathology seen in the WT mice, as it was found at similar concentrations in both mouse strains. However, endothelin-1, endoglin and matrixmetaloproteinase-9 were highly expressed in the WT mice, but not in the Kit mice forty five minutes post tMCAo. Further studies are required to elucidate whether the absence of these mediators is responsible for the reduced pathology in the Kit mice. In conclusion, the present study has provided an insight into mast cell responses following tMCAo, and has highlighted potential mechanisms by which mast cells mediate their response.

This thesis is primarily concerned with understanding the process of galaxy formation via the simulation of the interstellar medium, star formation and supernova feedback. In order to probe galaxy formation it is necessary that we first obtain a basic knowledge of the cosmological framework in which we are working. Therefore in chapter 1 we provide a brief overview of the salient features of the current cosmological paradigm in addition to discussing in some detail the physics of the interstellar medium. In chapter 2 we focus on the numerical methods necessary to perform accurate cosmological simulations. We begin by providing an overview of the different simulation techniques currently in use in the field before performing comparisons of two simulation codes that work via two completely different methods. We then introduce a code for generating high-resolution initial conditions for the simulation of individual objects and investigate the numerical effects of mass resolution in cosmological simulation. In chapter 3 we describe a statistical model of the interstellar medium, in which the conversion of cooling gas to stars in the multiphase interstellar medium is governed by the rate at which molecular clouds are formed and destroyed. In the model, clouds form from thermally unstable ambient gas and get destroyed by star formation, feedback and thermal conduction. In chapter 4 this statistical model is applied to the simulation of isolated disk galaxies. We show that it naturally produces a multiphase medium with cold clouds, a warm disk and hot supernova bubbles. We illustrate this by evolving an isolated Milky Way like galaxy. Many observed properties of disk galaxies are reproduced well, including the molecular cloud mass spectrum, the molecular fraction as a function of radius, the Schmidt law, the stellar density profile and the appearance of a galactic fountain. Finally in chapter 5 we perform an investigation into more dynamic situations, namely the evolution of gravitationally interacting disk galaxies and the formation of a galaxy in a fully cosmological simulation. It is found that the sticky particle model does a good job of reproducing many of the observed properties of interacting galaxies, including the properties of the ISM in the resulting elliptical galaxy.