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This Large Grant proposal combines the expertise of Sheffield and Leeds to establish a major electroceramics research hub. Electroceramics are advanced materials whose properties and applications depend on close control of crystal structure, chemical composition, ceramic microstructure, dopants and dopant (or defect) distribution. In most cases, properties depend on a complex interplay of structural, processing and compositional variables. They find applications in various physical forms, eg as ceramic discs, thick and thin films and multi-layer devices consisting of alternating layers (up to several hundred) of ceramic and metal electrodes. The particular property of interest may be a bulk property of the crystals, for example, high levels of ionic conductivity, mixed electronic-ionic conduction, ferro-, pyro- piezo-electricity or ferrimagnetism. Alternatively, it may relate specifically to the grain boundaries (or surface layers) in polycrystalline materials and to small differences in composition and therefore electrical behaviour between the bulk and grain boundary (or surface) regions. Such heterogeneous, or functionally-graded ceramics find many applications eg non-ohmic devices in current limiters such as varistors and thermistors. This proposal focuses on new and improved electroceramics for potential near- and long-term applications. The work will be carried out by a multidisciplinary team with complementary skills in materials discovery, modelling, processing and advanced characterisation. Such a multifaceted approach to electroceramics research and development does not exist in the UK within a single institution and the establishment of a 'hub' between the two universities will allow us to compete with the best in the world. Three work packages are proposed.I. New and improved bulk materials: structure-property relations, including: (a) novel perovskite-type materials with targeted functionality: ferroelectricity, reversible electro-strain, piezoelectricity, magneto-electric coupling and mixed conductivity; (b) development of new low temperature co-fired ceramics based on Sillenites; (c) oxygen nonstoichiometry and core-shell phenomena in doped BaTiO3; (d) development of improved lithium battery cathodes based on layered rock salt structures. II. Materials processing and development in thin and thick film form, including:(a) BiFeO3-PbTiO3 and BiMeO3 thin films for ferroelastic/ferroelectric switching for actuator and memory applications; (b) thin film feasibility studies on Solid Oxide Fuel Cell structures; (c) thick and thin films based on the novel ferroelectric system Ba2RETi2Nb3O15 to assess their potential device applications; (d) development of a masked Electrophoretic Deposition technique to deposit planar magnetoelectric composites based on Pb(Zr,Ti)O3-Pb(Ni,Nb)O3 (soft piezoelectric) and (La,Ca)MnO3 (magnetostrictor). III. Modelling of bulk materials and interfacial phenomena: (a) Development of Finite Element modelling of current pathways in (i) heterogeneous ceramics, (ii) local probe measurements within grains and across individual grain boundaries and (iii) multilayer devices; the results will be used to simulate Impedance Spectroscopy data and allow comparison with, and interpretation of, experimental data; (b) Modelling of functional oxides: point defects, electronic band structure calculations and mass diffusion in ceramics; this will underpin the experimental programmes on the development of new materials and the role of dopants in existing materials. Work packages I and II will be supported by a wide range of characterisation techniques available at Leeds and Sheffield for studying bulk and interfacial phenomena. New characterisation techniques will be applied: aberration-corrected TEM allows true atomic scale spectroscopy of interfaces and defects; Kelvin Probe Microscopy gives direct imaging of the work function variation in grain and across grain boundary regions.

The success of pervasive computing depends crucially on the ability to build, maintain and augment interoperable systems: components from different manufacturers built at different times are required to interact to achieve the user's overall goals.Pervasive systems often contain devices which must operate in very different environments and connect together in different ways, e.g., over ad-hoc wireless connections to a variety of systems, and still satisfy all the desired security and performance properties. Our approach to verifying these properties is to identify interoperability requirements for the interaction between the devices and their environment. These requirements introduce also an important layer of abstraction because they allow modularity in the verification process: it suffices to show that each mobile device or fixed component meets the interoperability requirements, and that the interoperability requirements entail the desired high-level properties.We argue that this verification framework makes it possible to adapt and extend techniques (such as model checking and process algebras) which have traditionally been used for verifying properties of small homogeneous systems, to large heterogenous systems. To support this thesis, we will develop techniques to verify properties concerning important aspects of heterogenous systems' security, individual and collective behaviour, performance and privacy. We will use the formal techniques to verify the consequent interoperability requirements, and evaluate their effectiveness through case studies.Note that our focus is on the verification of designs; in particular we focus on the design of basic component behaviours and the protocols which dictate access to them and interaction between them. It is important to note our intention is not to develop pervasive computing systems as such, but rather to draw motivation from, and test our ideas in, a number of planned and existing systems.Three case studies are planned; two are with industrial collaborators. The case studies will be drawn from three layers typical within pervasive systems: application, infrastructure and network. One industrial case study will be a healthcare application. One of its crucial features is the need for the monitoring device to operate in different environments. Hence a careful analysis of the necessary interoperability requirements is mandatory for this application. We will develop and apply our techniques as the system is designed, thus influencing directly the design of the application, motivating our techniques as we develop them, and gaining real life experience of applying our techniques in the field. In addition, our past experience indicates that we will also bring in further case studies, as the project develops. Drawing on the variety of expertise of the members of the consortium, we hope to make a step change in verification technology by developing novel techniques and learning which techniques are most effective in different contexts. The outcomes will directly benefit system designers, and indirectly, end users. They will include techniques applicable to a wide range of application domains, and results and lessons learned from three specific applications including a healthcare data capture system and RFID system infrastructure.

The burning of fossil fuels releases CO2 which is almost certainly responsible for anthropogenic climate change. Therefore, we must find alternative 'carbon-neutral' sources of energy as a matter of urgency. By far the largest potential source of renewable energy is sunlight. Harnessing this energy is one of the great challenges that our civilization faces, but using it is problematic. Existing silicon solar cells are expensive and inefficient, and do not produce fuel. Plants have hit on the perfect solution; they use the energy of sunlight to oxidise water (H2O), liberating O2, protons and electrons. The electrons and protons are used to fix carbon dioxide as organic sugars, which may then be used for biosynthesis or as fuel for respiration. The total process is known as photosynthesis. Plants can be grown to generate so-called 'biofuels' such as biodiesel, but this is inefficient, and competes with food production. What is needed is an artificial photosynthetic system, that, like plants, converts sunlight, water and CO2 into fuel, but is cheap, efficient and can be deployed over large areas. The proposed project is to create a vital component of a future solar energy conversion system. There are many components to the photosynthetic apparatus, but the main one of interest to this project is an enzyme called photosystem II (PSII). PSII is responsible for the light-driven water splitting reaction of photosynthesis. At its core, PSII has a cluster of one calcium and four manganese ions, which catalyse the water splitting reaction. This cluster is known as the oxygen evolving centre (OEC). The precise structure of the OEC and the mechanism of its action are still unknown, but both of these must be understood if a synthetic light-driven water oxidase is to be constructed. Building such a system is a vital prerequisite for the efficient large scale use of solar energy. The OEC in PSII is difficult to study, as PSII is a large complex containing many protein molecules and cofactors as well as the OEC. Therefore I propose to use small proteins as scaffolds for manganese ions, and so construct an OEC analogue that is uncoupled from the PSII enzyme and can be studied much more easily, and is a realistic prototype for future devices. Apart from PSII, there are many known enzymes which contain two manganese ions at their active sites, but PSII is unique in having four manganese ions at one site. I would like to take one of these simpler manganese enzymes and engineer it to bind more manganese ions, to mimic PSII. This can be accomplished by recombinant DNA technology. A DNA molecule with a sequence encoding the designed enzyme is constructed and then introduced into a harmless bacterium. The bacterium is then induced to produce the modified enzyme, which is then extracted and purified for further study. This technique has the advantage that DNA molecules are easy to manipulate, and specific sequences can be produced quickly and cheaply, allowing many designs of enzyme to be tried in a short time. Having produced a modified protein molecule that binds multiple manganese ions, the three dimensional structure can be determined. The protein will be probed for enzyme activity similar to that of PSII. I will try to catalyse the oxidation of water or other substrates using powerful oxidants as a substitute for light. In plants, chlorophyll is used as the main photosensitive pigment, but chlorophyll is usually unstable in artificial systems. Instead I will couple stable synthetic pigments to the protein and try to generate oxidative reactions using light. The results of these experiments can be related to the three dimensional structure of the enzyme and then used to to inform modifications in the design of the engineered proteins, which will then be subjected to further rounds of experimentation and design. This 'evolution by artificial selection', can be iterated until the desired goal of a soluble water oxidase is realised.

We inherit genes from our fathers and mothers and for most of our genes the copies we receive from either parent are equally active. An important exception to this general rule occurs in a process called genomic imprinting, whereby one gene copy is deliberately silenced. These imprinted genes are important in determining how the fetus grows and how infants adapt their physiology to life outside the womb. But the fact that these genes have one copy that is preselected to being silent poses a risk and makes them particularly vulnerable to mutation events, such as occurs in cancer. Imprinted genes behave in this manner because they are marked in different ways in the male and female germ cells (sperm and eggs). How these genes are so marked is not fully known, and it is important to find out, because if the marking process goes wrong problems in fertility or developmental abnormalities may arise. By analysing a single imprinted gene in some detail, we have discovered an important part of the mechanism in the germ cell marking event. In this research, we wish to understand this mechanism in more detail and we need to show that it could apply generally to imprinted genes. This work will be done in a model system, but it will provide important new insights for human studies.

Light is a versatile tool for imaging and engineering on microscopic scales. Optical microscopes use focused light so that we can view specimens with high resolution. These microscopes are widely used in the life sciences to permit the visualisation of cellular structures and sub-cellular processes. However, the resolution of an optical microscope is often adversely affected by the very presence of the specimen it images. Variations in the optical properties of the specimen introduce optical distortions, known as aberrations, that compromise image quality. This is a particular problem when imaging deep into thick specimens such as skin or brain tissue. Ultimately, the aberrations restrict the amount of the specimen that can be observed by the microscope, the depth often being limited to a few cellular layers near the surface. This is a serious limitation if one wants to observe cells and their processes in their natural environment, rather than on a microscope slide. I am developing microscopes that will remove the problematic aberrations and enable high resolution imaging deep in specimens.Focused light also has other less well-known uses. It can be used to initiate chemical reactions that create polymer or metal building blocks for fabrication on the sub-micrometre scale. These blocks, with sizes as small as a few tens of nanometers, can be built into structures in a block-by-block fashion. Alternatively, larger blocks of material can be sculpted into shape using the high intensities of focused lasers. These optical methods of fabrication show potential for use in the manufacture of nanotechnological devices. When manufacturing such devices, the laser must be focused through parts of the pre-fabricated structure. The greater the overall size and complexity of the structures, the more the effects of aberrations degrade the precision of the fabrication system. My research centres on the use of advanced techniques to measure and correct such distortions, restoring the accuracy of these optical systems.Traditional optical systems consist mainly of static elements, e.g. lenses for focusing, mirrors for reflecting and scanning, and prisms for separating different wavelengths. However, in the systems I use the aberrations are changing constantly. Therefore they require an adaptive method of correction in which the aberrations are dynamically compensated. These adaptive optics techniques were originally developed for astronomical and military purposes, for stabilising and de-blurring telescope images of stars and satellites. Such images are affected by the aberrations introduced by turbulence in the Earth's atmosphere. The most obvious manifestation of this is the twinkling of stars seen by the naked eye. Recent technological developments, such as compact and affordable deformable mirrors for compensating the optical distortions, mean that this technology is now being developed for more down-to-Earth reasons. This has opened up the possibility of using adaptive optics in smaller scale applications.In conjunction with researchers in Japan and Australia, I will develop adaptive optical fabrication systems that will be able to produce complex micrometre-scale structures with greater accuracy than was previously possible. With biologists in the University of Oxford, I will use adaptive optics to increase the capabilities of microscopes in imaging deep into thick specimens. This will enable biologists to learn more about the processes that occur within cells and the development of organisms. The aberration correction technology will also have use in other areas such as medical imaging, optical communications and astronomy.

Ubiquitous computing (ubicomp) concerns the embedding and distribution of computing into the world around us. The Mixed Reality Laboratory (MRL) at the University of Nottingham has been at the forefront of international ubicomp research for the past six years, creating new ubiquitous devices, establishing the distributed software platforms that are required to knit many such devices together, working with external partners to demonstrate innovative and creative applications of ubicomp, and studying these and then generalising the lessons learned into new design concepts and frameworks. Much of this research has been carried out within EPSRC's Equator project, a six-year, ten million pound Interdisciplinary Research Collaboration that involved eight UK universities and that was led by the MRL. Through Equator and other projects we have successfully laid the foundations for a new interdisciplinary approach to ubicomp research that involves taking emerging technologies out of the laboratory and studying them 'in the wild'. In so doing we have placed the UK in a world-leading position in this field.Following the end of Equator, the MRL is seeking platform funding to sustain its research capacity by retaining and further developing key interdisciplinary researchers and by undertaking speculative new projects to chart out the major new challenges that will arise as ubicomp moves from its current state of isolated installations that are maintained by researchers to being widespread and managed by end-users. At the heart of this emerging agenda are the three research challenges of exploring the temporal, spatial and material expansion of ubicomp. These will be charted through a program of speculative pilot projects, sensitising studies and research challenge sandpits. This will be complemented by a focus on developing collaborations where we will work with external partners to explore two key application domains, the creative industries and everyday living. Finally, we will use platform funding to strengthen our core research capacity, developing our research staff and enhancing our supporting methods and software tools. This programme of activities will enable the MRL to continue to shape the agenda for ubiquitous computing over the next five years and the UK to remain at the forefront of research in this rapidly growing field.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

Doctoral Training Partnerships: a range of postgraduate training is funded by the Research Councils. For information on current funding routes, see the common terminology at https://www.ukri.org/apply-for-funding/how-we-fund-studentships/. Training grants may be to one organisation or to a consortia of research organisations. This portal will show the lead organisation only.

P and type 1 pili are surface fibers of uropathogenic Escherichia coli (UPEC) bacteria that play essential roles in the onset of bacterial infection by mediating attachment to the host kidney (P pili) and bladder (type 1 pili). UPEC are the primary causative agents of urinary tract infections (UTIs), which account for an estimated 8 millions physician-office visits and 100,000 hospital admissions every year in the US or in Europe. Indeed, it has been estimated that 1 in 2 women will contract a UTI during their lives, and that 20-40% of these will experience one or more recurrent infections. P and type 1 pili are assembled by a mechanism that also functions in the biogenesis of surface organelles in many other bacterial pathogens, including the potential bioterrorism agent Yersinia pestis. Our research programme focuses on two essential goals: i- understanding how pili are assembled at the surface of the bacterium, and ii- discovering novel antibiotics, which will specifically target the assembly of pili. Assembly of pili requires two specialist proteins: a chaperone that takes up each pilus subunit and ferries them to a site of assembly, and a membrane pore protein termed ?the usher? that serves as assembly platform and site of assembly. In the past we have made significant progress in understanding how the chaperone works. We will therefore focus our research on the usher. Indeed very little is know as to how this membrane protein carries out selection of the subunits, their assembly in a defined order and their secretion through the membrane. Another goal of this research is the discovery of novel antibiotics able to inhibit pilus biogenesis. Such antibiotics would be very useful as they will disarm the bacterial pathogen only, instead of killing all bacteria (the gut flora includes beneficial bacteria) as is the case for the antibiotics presently available. The added advantage of targeting virulence factors is that the selective pressure for development of resistance is thought to be considerably lowered. These two goals of our research will have considerable impact on public health. We expect that the research will not only shed light on the processes that lead to disease but also will help understand how secretion through cell membranes, a biological process occurring in all realms of life, is carried out.

Flooding caused by heavy convective rain is a serious problem in the UK. Flash floods in hilly terrain can be particularly damaging. The Convective Orographically-induced Precipitation Study (COPS) is an international project designed to address this problem and to improve predictions of heavy convective precipitation. This proposal is the UK component of COPS which adds specific objectives complementary to those of other COPS partners. It will produce an understanding of the processes that control the formation and development of convective precipitation over hilly terrain which will be used by scientists within the Mesoscale Modelling group of the Met Office in reducing uncertainty in predictability of convection over complex terrain with the Unified Model (UM). This will be achieved by synthesising COPS data alongside modelling activities focussed on interpreting the data. The problem involves five integrated parts that need to be tackled together. (1) The thermally driven flows in complex terrain depends critically on the surface exchanges of heat and water. (2) The composition and size distribution of the aerosol particles have a crucial influence on the microphysics and dynamics of the convective clouds and particularly the amount of precipitation. (3) The thermals and other features in the boundary layer that transport heat, moisture and aerosols to the convective clouds. (4) The development of precipitation depends critically on the detailed microphysics and dynamics of the convective clouds. (5) Finally, reducing uncertainty in predictability of the location and timing of convective storms in hilly terrain with the UM, depends on the knowledge gained from these four parts. In particular the relative contributions of different sources of uncertainty in predictability of convective storms in hilly terrain will be quantified, thus providing the basis for an ensemble forecast system.