The proportion of elderly people in our society is increasing. As a result there is an increase in the number of people with age related degenerative diseases that cause dementia. It is known that dementia, in certain circumstances, can be inherited and run in families. Approximately 750,000 people in the UK have some form of dementia, the most common and widely known is Alzheimer?s disease. Thankfully, a lot of progress has been made in understanding the genetic cause of Alzheimer?s disease. The second most common form of dementia is called frontotemporal dementia or FTD. It can affect people?s behaviour and ability to speak. About half of all people with FTD have other family members with this disease, therefore, there is a large inherited (genetic) reason for the development of this disease. We know around 10% of cases of FTD are caused by errors in a gene called tau, however, we know nothing about the remaining 90%. There are reports of families with FTD showing there is a gene problem on chromosome 17, where the tau gene lies. However, nobody has been able to find any errors in the tau gene in these families. I will analyse the entire tau gene, more thoroughly than has been done before, and will check nearby genes to identify the disease causing error. The second part of my project is as follows; By testing a large collection of FTD patients collected from around Manchester I have shown there is a gene causing FTD with motor neuron disease on chromosome 9, consistent with a report from the US. By identifying common regions of chromosome 9 shared by patients from Manchester, and screening the genes within these regions, I hope to identify the disease-causing gene. Finally, it has been reported that errors in a gene called VCP can cause a bone disease and FTD in some patients. I will screen the Manchester FTD patients to see if VCP is causing disease in any of them. In summary, it is important to find genes causing FTD because it is a common form of dementia with a large genetic component to its cause. By identifying these genes we will find the primary cause of, and gain understanding to, the biological problem reason of disease. This knowledge will help in diagnosis and in the development of systems to produce a treatment, which will ultimately help people affected by this illness.

Many current and next generation energy systems are reliant on the production, transportation, storage and use of gaseous hydrogen, often at high pressure. The safety, durability, performance, and economic operation of such systems are challenged due to the reality that hydrogen promotes a variety of degradation modes in otherwise high performance materials. Such degradation is often manifested as cracking which compromises the structural integrity of metals and polymers; a behaviour complicated by time and operating cycle (e.g., stress, hydrogen pressure, and temperature) dependencies of degradation. As an example, concurrent stressing and hydrogen exposure at typical pressure vessel or pipeline environmental conditions can promote cracking in modern metallic systems at one-tenth the fracture toughness. Such hydrogen-induced degradation phenomena are generally categorised as hydrogen embrittlement. The breadth and importance of hydrogen damage phenomena have not gone unnoticed in the scientific community with an immense amount of work conducted over the past 100 years. The problem is broadly interdisciplinary and such work has involved metallurgy, chemistry, solid mechanics and fracture mechanics, surface science, molecular and atomic hydrogen physics, non-destructive inspection, materials characterisation, and mechanical-properties testing. This important work notwithstanding, major challenges face those tasked with managing complex engineering structures exposed to demanding environment and mechanical loading conditions. The challenge here is to transform debate on mechanisms of hydrogen damage into a focus on quantitative, predictive models of material cracking properties. Overarching these challenges is the inescapable fact that hydrogen damage problems are immensely complex, requiring understanding of time-cycle dependent processes operating at the atomic scale to impact behaviour manifest at the macroscopic scale.

**The project is partly funded by The National Nuclear Laboratory** Nuclear data, including neutron cross sections, underpin the nuclear fuel cycle, allowing calculations, predictions and analyses to be performed. These cross sections must be known to the highest possible accuracy and this is reached by performing cutting edge experiments. This PhD project focuses on neutron cross section measurements on isotopes of particular relevance to the UK nuclear industry.Neutron cross-section measurements will be performed at facilities such as the thermal high flux research reactor at ILL, Grenoble and the neutron time-of-flight facility n_TOF at CERN, Geneva. The first cross section to be measured will be 13C, of particular importance to aid characterization of the irradiated graphite from graphite moderated reactors such as AGRs. Further isotopes requiring an improvement in their cross section accuracies have been identified such as 35Cl, 39Ar and 59Fe. As part of the PhD, future needs will be identified and measurements planned/performed. There will also be the opportunity to be involved in the applied nuclear physics groups research measuring nuclear fission properties with the fission fragment spectrometer, STEFF which has an on going research program at n_TOF, CERN

The project objective is to find a model to describe the propagation of a fluid in a crack or a fracture in a concrete material. In the Sellafield site, concrete material is extensively used to contain radioactive wastes. Nevertheless, while a thick concrete layer represents a good protection against alpha, beta and, gamma radiations, it also exhibit structural defects like cracks and fractures. To guarantee the safety of the nuclear site, we need to understand how the material waste contained in a pond surrounded by concrete walls propagates/infiltrates inside the cracks and fractures of the walls. Moreover, we also need to pin down the impact of that infiltration phenomenon on the concrete. To this goal, two model of cracks may be considered. In the first model, the geometry of the crack is fixed and we would like to determine how deep the fluid goes inside. In the second model, the geometry of the crack is time dependent and therefore can vary. The objective with this second model is to determine first how fast the geometry of the crack evolves and then how it influences the propagation of the fluid inside.

In order for the nervous system to function properly, different types of neurons need to be produced and the right connections need to be made between them, so that a functional circuit, not dissimilar to an electrical circuit, can be formed. For this to happen, neurons use long extensions of their cell bodies, called axons. These are dynamic processes that can grow quite long and navigate through the tissue, until they find the right cells to form connections with. The generation of several different types of neurons relies on the activity of a set of key proteins termed Transcription Factors. These proteins are special in the sense that they drive the production of several other proteins by the cell. Transcription factors achieve this by binding to DNA, which is then translated by the cell?s machinery into making a particular protein. There are thousands of transcription factors known, each with a preference for a particular sequence of DNA, and therefore able to influence the production of different sets of proteins. The DNA of a cell is in the nucleus therefore, transcription factors are also found in the nucleus. In fact, the conventional view is that transcription factors only have a function in the nucleus. We have been investigating the role of a transcription factor, Foxg1, which is important for the generation of neurons in the brain in all animals. Depending on when this gene malfunctions in humans, the brain may fail to form, or cancer or mental retardation can arise. We have recently made the unexpected discovery that FoxG1 is not only found in the nucleus, as expected for conventional transcription factors, but it is also found in the axons of brain neurons. In this proposal, we will ask 3 questions; in which neurons exactly is FoxG1 found in the axon, how does it get there and finally, what does it do? From the thousands of transcription factors known, only a handful have been shown to have an ?extra-nuclear? function in axons. Their precise function there is not quite clear yet, but it seems that they help the axon grow in the right direction. Our proposed work will have two benefits; it will increase our understanding of the function of a key brain transcription factor and will further our understanding of the unconventional role that transcription factors may have in axonal development.