Prof Blackshaw has identified mechanisms of visceral afferent function in animal models and how hypersensitivity occurs in disease. He has discovered subtypes of sensory endings in mucosa, muscle and vasculature. This work has provided a detailed knowledge of the structure and function of visceral sensory nerves, demonstrating that vascular endings transduce exclusively painful signals whereas muscular and mucosal endings detect mainly innocuous events. By joining the London group, he has a uniq ue opportunity to study the anatomy, physiology and molecular makeup of visceral afferents in human tissue. This is crucial for improvement in knowledge and treatment of CVP. Human bowel specimens will be acquired from surgery, and in vitro recordings made from afferent fibres in optimized recording setups. This will allow categorization according to mechano- and chemo-sensitivity, and how these parameters change in disease. He will focus on how afferents are activated or modulated by receptor and ion channel ligands. In parallel, the structure of afferent endings will be studied by immunohistochemistry and the localization of molecular targets correlated with their function. We expect finding drug targets on sensory nerves will lead more directly to development of therapeutic agents, since we shall know their relevance to human disease.

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The theory of operator algebras goes back to Murray, von Neumann, Gelfand and Naimark. The original motivation was to provide a mathematical foundation for quantum mechanics. At the same time, from the very beginning of the subject, it was anticipated that operator algebras form very interesting structures on their own right and will have applications to unitary representations of groups and operator theory in Hilbert space. Actually, much more turned out to be true. After some dramatic and unexpected developments, the theory of operator algebras has established itself as a very active and highly interdisciplinary research area. Not only do there exist - as initially envisioned - strong connections to quantum physics as well as representation theory and operator theory, operator algebras nowadays have far reaching applications in various mathematical disciplines like functional analysis, algebra, geometric group theory, geometry, topology or dynamical systems. One of the most important classes of operator algebras is given by C*-algebras, which are defined as norm-closed, self-adjoint algebras of bounded linear operators on a Hilbert space. As in many areas in mathematics, advances in the theory of C*-algebras went hand in hand with the discovery of interesting and illuminating examples, the most prominent ones being group C*-algebras and C*-algebras attached to dynamical systems, so-called crossed products. The main objects of study in this research project are given by semigroup C*-algebras, which are natural generalizations of group C*-algebras. Our goal is to analyse the structure of semigroup C*-algebras and to use this construction as a tool to study groups and their subsemigroups from the point of view of geometric group theory. Closely related to this, this project also aims at a better understanding of the interplay between C*-algebras and dynamical systems. Our project lies at the frontier of current research. We take up recent advances in semigroup C*-algebras, classification of C*-algebras, the interplay between C*-algebras and symbolic dynamics, as well as the discovery of rigidity phenomena in operator algebras and dynamical systems. One of the key characteristics of our research project is its high interdisciplinary character. It lies at the interface of several research areas in mathematics and brings together expertise from different fields. This takes up the trend in mathematics that interactions between different branches are becoming more and more important. Therefore, the mathematical community as a whole benefits through an active and inspiring exchange of ideas.

The impacts of climate change, and warming in particular, on natural ecosystems remain poorly understood, and research to date has focused on individual species (e.g. range shifts of polar bears). Multispecies systems (food webs, ecosystems), however, can possess emergent properties that can only be understood using a system-level perspective. Within a given food web, the microbial world is the engine that drives key ecosystem processes, biogeochemical cycles (e.g. the carbon-cycle) and network properties, but has been hidden from view due to difficulties with identifying which microbes are present and what they are doing. The recent revolution in Next Generation Sequencing has removed this bottleneck and we can now open the microbial "black box" to characterise the metagenome ("who is there?") and metatranscriptome ("what are they doing?") of the community for the first time. These advances will allow us to address a key overarching question: should we expect a global response to global warming? There are bodies of theory that suggest this might be the case, including the "Metabolic Theory of Ecology" and the "Everything is Everywhere" hypothesis of global microbial biogeography, yet these ideas have yet to be tested rigorously at appropriate scales and in appropriate experimental contexts that allow us to identify patterns and causal relationships in real multispecies systems. We will assess the impacts of warming across multiple levels of biological organisation, from genes to food webs and whole ecosystems, using geothermally warmed freshwaters in 5 high-latitude regions (Svalbard, Iceland, Greenland, Alaska, Kamchatka), where warming is predicted to be especially rapid,. Our study will be the first to characterise the impacts of climate change on multispecies systems at such an unprecedented scale. Surveys of these "sentinel systems" will be complemented with modelling and experiments conducted in these field sites, as well as in 100s of large-scale "mesocosms" (artificial streams and ponds) in the field and 1,000s of "microcosms" of robotically-assembled microbial communities in the laboratory. Our novel genes-to-ecosystems approach will allow us to integrate measures of biodiversity and ecosystem functioning. For instance, we will quantify key functional genes as well as quantifying which genes are switched on (the "metatranscriptome") in addition to measuring ecosystem functioning (e.g. processes related to the carbon cycle). We will also measure the impacts of climate change on the complex networks of interacting species we find in nature - what Darwin called "the entangled bank" - because food webs and other types of networks can produce counterintuitive responses that cannot be predicted from studying species in isolation. One general objective is to assess the scope for "biodiversity insurance" and resilience of natural systems in the face of climate change. We will combine our intercontinental surveys with natural experiments, bioassays, manipulations and mathematical models to do this. For instance, we will characterise how temperature-mediated losses to biodiversity can compromise key functional attributes of the gene pool and of the ecosystem as a whole. There is an assumption in the academic literature and in policy that freshwater ecosystems are relatively resilient because the apparently huge scope for functional redundancy could allow for compensation for species loss in the face of climate change. However, this has not been quantified empirically in natural systems, and errors in estimating the magnitude of functional redundancy could have substantial environmental and economic repercussions. The research will address a set of key specific questions and hypotheses within our 5 themed Workpackages, of broad significance to both pure and applied ecology, and which also combine to provide a more holistic perspective than has ever been attempted previously.

To develop a solution to the problem of prohibitively low energy density of polymer capacitors, which frustrates their integration into high power converters and inhibits progression to an all-electric future.