Photonic materials interact with light in useful and interesting ways. They enable its manipulation, and conversion into other forms of energy. One important class of photonic materials are non-linear optical (NLO) materials, which can be used to manipulate and adjust the properties of laser light beams. For example, they are used to make green lasers by second harmonic generation (SHG) from an infra-red source, and in electro-optic (EO) modulators that transfer digital electronic signals into fibre-optic telecommunications. At present, most commercial NLO materials are simple inorganic salts. These are inexpensive, durable and ideal for simple SHG applications. However, in telecommunications and computing they suffer from slow speed, as their responses originate from displacement of (relatively heavy) ions in response to the electric field of light. Molecular organic and metal-organic materials promise faster responses, because they arise from displacement of lighter, faster electrons, and also rational property tuning and the possibility of rapid property switching (i.e. on/off for optical or electrooptical transistors). But it is difficult to obtain molecules combining high NLO activity with adequate transparency and photostability, and adding the ability to reversibly switch between on/off states is a still greater challenge. Recently, we discovered a promising new class of molecular NLO materials based on polyoxometalates (POMs) - a type of molecular metal oxide cluster - connected to organic groups. These POM-based chromophores (POMophores) obtain high NLO coefficients from materials with small, stable organic groups and excellent transparency, and show redox properties that could be used to switch the NLO response. The next stage, addressed in this project, is to assemble POMophores into bulk materials that can be used in devices - specifically EO modulators and transistors. To do this, we must find a way to align all of the POMophores so that they point in the same direction and give a net NLO effect. This is challenging, as methods for controlled assembly of POM-based materials are currently very limited, and to achieve the goal we will develop a new approach where we first trap the POMophore in a molecular container. The molecular containers are designed in such a way that they form a film where the desired molecular orientation is forced on the POMophore. In addition to organising the POMophores to give bulk NLO properties, the containers will also protect them from degradation when we investigate redox-switching of the NLO response. POMs offer many other properties beyond non-linear optics - for example many POM clusters are excellent catalysts or photocatalysts due to their ability to rapidly accept and transfer electrons, some have magnetic and/or luminescence properties introduced by incorporating suitable heterometals into the POM framework, and POMs have also demonstrated anti-viral activity. Therefore, we expect that other areas of chemistry and materials science will benefit from methods enabling their encapsulation and control over their positioning on the nanoscale. Possibilities could include selective catalysis, solar energy conversion, memory devices, and even targeting of biologically/medicinally active POM species for therapeutic interventions. This project will lay the groundwork necessary for such developments, as well as potentially producing the new, high performance bulk NLO materials needed for future telecommunications and computing.

This project brings together art historians and musicologists to develop new methods for the historical study of sensory experiences. To do this, we will focus on art and music in the Southern Low Countries (roughly present-day Belgium) between 1350 and 1700. But why do we need such a project? First it is important to note that, over the past decade, there has been much fruitful historical work on the senses, especially in the medieval and early modern periods. Yet most historians in this field privilege written sources over music, printed imagery, art and architecture. Even when they do use such material it is often approached as if it were text rather than something experienced by the senses. Musicologists and art historians are ideally placed to address this problem. We are experts at patient looking and listening, a process termed 'formal analysis' in both disciplines. Such analyses are normally anchored in specific historical knowledge about the makers and consumers of art and music. But what are the similarities and differences between how musicologists and art historians perform their historically grounded analyses? And how can we learn from one another to refine existing and develop new methods of enquiry so as to benefit the broader exploration of the history of the senses? This matters because comparing how we interpret works of art and music will offer a deeper, more nuanced understanding of how sensory experiences informed medieval and early modern European culture. The academic disciplines of history, art history and musicology developed as distinct in the nineteenth century. Yet in the period and area covered by this project such scholarly boundaries did not exist. Painting, sculpture and architecture were increasingly defined as 'fine arts' and, to bolster their prestige, were often linked to music, studied as a 'liberal art' at universities from the middle ages onwards. At the same time, music and art circulated widely: poor people earnt their keep by singing popular ditties or selling cheap woodcut imagery while prelates and princes built sumptuous interiors for grand musical performances. To explore all this, we shall focus on the Southern Low Countries between 1350 and 1700. It is, quite simply, ideal for pursuing our aims. During the period covered by this project, this region was a powerhouse of art, music, literature, manuscript illumination and printing. Moreover, these art forms were closely related. Painters like Jan van Eyck and Hugo van der Goes composed scenes of angelic music-making while the music scribe Petrus Alamire supplied elite customers across Europe with richly decorated musical manuscripts. Princely courts across Europe vied to attract composers such as Josquin des Prez, Jacob Obrecht and Orlandus Lassus. Crucially, artists, architects, print-makers, musicians and builders of musical instruments often moved in the same social circles. For instance, in Antwerp - the most populous city in northern Europe in the sixteenth century - music-printers, harpsichord builders and painters were all organized under the Guild of St Luke. At the end of the fifteenth century, this guild had merged with a literary society called 'De Violieren' with a socially diverse membership ranging from panel-makers' apprentices to urban patricians. Together they wrote poetry, plays and songs to be performed outdoors, on public stages set in important urban spaces and self-consciously addressed to the full social spectrum of the city, including children, women and immigrants from as far as Asia and Africa. In turn, these public stages were often designed and decorated with imagery and sculptures made by fellow guildsmen of 'De Violieren'. It is this wealth of visual, spatial, textual and musical sources that makes the Southern Low Countries the perfect laboratory for developing new, sensorially informed research methods applicable across history, art history and musicology.

While rare earth metals are used in relatively small quantities, they play a major role in cutting edge technologies, such as electronics, information technology and in automobile industries. These metals are used in the high-powered magnets used in computers, they are components of wind-turbines and electric cars, they are used in fluorescent lights and in several catalytic processes. Roughly 86% of all rare earths come from China. This has been recognised as a significant risk to be so dependent on one country. Unfortunately the UK possesses very few rare-earth containing minerals, but what it can do to become more self-sufficient is to recycle the rare-earths that are in waste-piles. Currently the UK has little activity in this area, but recent parliamentary reports draw attention to the need for protecting the supply of rare earths and one foresees a growing effort in this area. The UK does possess, however, a strong scientific base in the reprocessing of nuclear fuel using liquid-liquid extraction. We have worked in this area, alongside the National Nuclear laboratory. The knowledge gathered from these activities can usefully be re-chanelled into designing efficient extraction methodologies for the chemically-related rare earths. This is our intention. We will focus on the extraction of the rare-earth, Samarium, from waste high-powered magnets using ionic liquids as extractants. Our aim to to scale-up the chemical processes currently investigated by the Binnemans group in Leuven, Belgium. While we believe our general methodology can usefully be applied to many, disparate processes, our focus will be on three systems. Our proposal is firstly to study these systems at a molecular level, using molecular dynamics simulations, to understand the molecular structures that form during the extraction process. Secondly we shall use these insights to construct soundly based, reliable thermodynamic models so that we can predict system properties over a range of temperatures and compositions. Thirdly we will simulate and evaluate an industrial-scale extraction process, incorporating these models. Finally, one the basis of these models, we will liaise with the Binnemans group so that yet more optimised ionic liquids can be synthesised for rare earth extractions.

The elements we see around us, and that constituent our bodies, are predominantly stable, yet we know these were forged in violent astrophysical scenarios. The traces from this violent history can be found in sensational new detailed astronomical observations of element abundances from exploding stars, meteoritic inclusions attributed to condensation of material following single explosive events, and observations of gamma-ray emission indicating these process are still ongoing in our universe. The synthesis of the elements in these explosive scenarios involves nuclear reactions involving unstable nuclei. The unknown structure and reactions of these unstable nuclei critically affects our understanding of the origin of elements we now see in a relatively quiescent state around us, and the nature and dynamics of the stellar environments in which they formed. As we have begun to explore the properties of these nuclei, surprising results have been found on the evolution of shell structure, indicating what we find to be the case in stable nuclei, cannot be simply extrapolated to unstable systems. Nature is far more rich and diverse then we anticipated, leading to new shell structures driven by the underlying nature of the nuclear interaction. The locations of these shell structures are subtle and intimately associated with the shapes of nuclei. One such example are Pear-shaped nuclei exhibiting permanent static octupole deformations.These provide a very promising laboratory to search for finite atomic electric dipole moments, indicative of CP violation beyond the Standard Model of Particle Physics. The science described above requires precision measurements of the structure and reactions of unstable nuclei. Furthermore, the studies need to be performed in the appropriate energy regime where these properties can be best probed. The new TSR heavy ion storage ring will be located at the ISOLDE facility CERN. This will be a unique facility worldwide. ISOLDE is the world's leading facility for the production of radioactive beams. Following new upgrades, these radioactive beams will be accelerated to the energy range perfect for precision reaction studies. These beams will be injected into the storage ring where they can be rapidly cooled to give very high quality radioactive beams enabling ultra high resolution measurements. For heavy radioactive species, the beam extracted from the storage ring will be allied to a novel solenoidal magnet and detection system. The ISOL-SRS spectrometer systems proposed by the UK community for use in conjunction with the TSR storage ring will enable a major breakthrough in precision studies of the reactions and properties of unstable nuclei across the vast range of masses and isotopes produced by the ISOLDE radioactive beams facility, CERN.

Blood clotting occurs in response to blood vessel damage. This requires the specific recruitment of platelets (specialised blood cells) to the site of injury as one of the first (of many) events that prevents bleeding. This process is highly dependent upon a protein known as von Willebrand factor (VWF) that circulates in blood. The ability of VWF to perform this task is regulated by an enzyme that is also present in the blood, ADAMTS13, and that, under very single substrate specific circumstances, cleaves VWF into smaller forms that are less capable of recruiting platelets. Clinically, deficiency in VWF is the most common inherited bleeding disorder, whereas people with ADAMTS13 deficiency suffer from a life-threatening thrombotic disorder with a ~90% mortality rate. More subtle differences in the blood levels/function of VWF and ADAMTS13 are also important determinants of an individual's risk of bleeding and thrombosis, and also influence the likelihood of both heart attack and stroke. ADAMTS13 is a very highly specific proteolytic enzyme that cleaves only one protein (VWF) and does so at just a single site, and even then, only under very specific conditions of blood flow. ADAMTS13 is made up of multiple domains. The metalloprotease domain of this enzyme contains the active site that cleaves VWF, whereas the other variably contribute to the binding of ADAMTS13 to VWF. Despite this knowledge, how ADAMTS13 recognises and cleaves VWF so specifically remains unclear. To understand this at a molecular level, we will ascertain the structure of different domains fragments of ADAMTS13, both in free forms and in stabilising complexes with specific antibody fragments that can aid in determining structures. In addition, we will also elucidate the structure of ADAMTS13 fragments whilst bound to the corresponding fragments of VWF. We will characterise the binding and cleavage of these VWF fragments by ADAMTS13 and also explore the influence of calcium binding to this process. The information from this project will provide important insights into how ADAMTS13 functions at a molecular level its unique single substrate specific cleavage of VWF. This data will provide the opportunity to rationally engineer ADAMTS13 to improve its efficacy as a therapeutic agent, for which it is currently under development as a more specific clotbuster for the treatment of thrombotic disease.