With the UK committed to reducing its reliance on fossil fuels by 2050, there must be a commensurate increase from other energy sources to maintain and provide for increased energy requirements, at the same time increasing the diversity in energy sources. As a mature and clean energy production method, nuclear power will no doubt make a significant contribution to the UKs energy portfolio. The UK currently operates a civil nuclear fleet consisting primarily of advanced gas reactors (AGRs). Any new nuclear build in the forseable future will likely be new Pressurised Water Reactor (PRW), such as the Westinghouse AP1000 or Areva European Pressurised Reactor (EPR). Both reactors are designed to run using UO2 fuel types enriched with fissile uranium to ~3-5%. In addition to these generation III and III+ type of reactors, some fourth generation (GenIV) reactor types are designed to operate using UO2 fuels (3 out of the 6 final designs). Furthermore it is becoming more desirable by plant operators to increase the level of burn-up in the fuel, not only increasing the efficiency of the reactor, but also reducing operating costs and minimising the volume of nuclear waste produced. One key factor limiting higher burn-up of nuclear fuel is the production and accumulation of fission products within the fuel that can significantly affect the physical properties and limit performance. Broadly speaking, there are four different characteristic fission products produced during burn-up: gaseous, metallic precipitates, oxide precipitates, and those in solid solution. The work to be undertaken here examines the behaviour of fission products under irradiation in both a non-radioactive model nuclear fuel simulant (ceria) and in simulated and real spent nuclear fuel. These materials will be fully characterised, both structurally and chemically, through a combination of transmission electron microscopy and atom probe tomography, with the results being fed back to modellers to validate and/or benchmark predictive models for in-core performance of the fuels, such as ENIGMA. The behaviour of nanocrystalline materials under irradiation will also be investigated. Nanocrystalline materials are viewed to be a viable route towards radiation tolerance, and may therefore improve safety, due to the high number of grain boundaries and interfaces present acting as efficient sinks for defects. It is therefore critical that information on the radiation response of nanocrystalline materials is obtained if this class of materials is to be used in nuclear reactors as a means to improve reactor safety. This characterisation of the materials in the as-received and irradiated state will be performed using the electron microscopy and atom probe capabilities at Oxford University. The ceria samples will be provided by the Universities of Nebraksa and Sheffield, and the real/synthetic/simulated fuels samples will be provided by the National Nuclear Laboratory. The NNL - who will benefit significantly from the results to be obtained from this project - will provide advice in the safe handling of radioactive material, and will provide access to the hot/active transmission electron microscope at the Sellafield central laboratory for characterisation of active samples.

HIV/AIDS is described by the World Health Organisation as a global pandemic. Estimates show that over 25 million people have died since 1981 and over 33 million people including adults and children are currently living with the disease. In 2005, AIDS claimed an estimated 3.3 million lives globally, including more than 570,000 children. The prevalence of HIV/AIDS continues to increase and it is expected that over 90 million will ultimately be infected in Africa alone. The UK had the highest growth in HIV/AIDS infection in western Europe in the period between 2001 - 2007 with a 64% increase. HIV treatment suffers from many issues including the need for patient compliance with a very strict regime of medication. HIV mutation leads to resistance to existing therapies but the ability of therapies to target HIV in the body is critical to the success of medication. HIV resides in various sites throughout the body but there are both cellular and tissue sites which are particularly difficult for drugs to reach. These so called 'sanctuary sites' have the potential to be targeted by particles of drug, rather than dissolved drug molecules. Cancer research has shown the benefits of particulate nanomedicine drug delivery approaches. The use of nanoscale polymer carriers which act as vehicles to transport and deliver poorly soluble drugs to the desired site of action, has been beneficial for tumour targeting as the particle nature of the nanomedicine drives the accumulation in tumour tissues. Cellular and tissue sanctuary sites in HIV infection have been widely speculated to also be ideal candidates for particle-based approaches but there has been limited work in this area. Branched polymers may operate as particle-like drug delivery vehicles and many have been shown to have therapeutic advantages. The best materials are however very expensive to synthesise and would not be viable for treatments in populations such as the sub-Saharan regions (over 20 milllion HIV infections) where cost is a critical component of treatment choice. The University of Liverpool has developed a new class of materials, Polydendrons, that offer many of the benefits of the most sophisticated branched polymers, but can be produced relatively cheaply. In early work, prototype materials have been produced with particle sizes of >40nm and encapsulation capabilities. These materials are unique and still at a very early stage of development. This proposal will simultaneously explore the synthesis of Polydendrons and their ability to intervene in HIV treatments. They will be studied as drug carriers of specific size, shape and surface functionality and their ability to target HIV in sanctuary sites will be established. A collaboration between the departments of Chemistry and Molecular and Clinical Pharmacology over 4.5 years is proposed with input from global pharmaceutical companies and HIV clinicians. This approach of material synthesis with integrated pharmacology will considerably accelerate the development of potential new therapies leading to a leading position for the UK that will be applicable to other health issues such as cancer, tuberculosis and hepatitis C.