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During the last twenty years mathematics and physics have significantly influenced each other and became highly entangled. Mathematical physics was always producing a wide variety of new concepts and problems that became important subjects of the pure mathematical research. The growth of gauge, gravity and string theories have made the relation between these subjects closer than ever before. An important driving force was the discovery of quantum groups and of the gauge/gravity dualities. Here the leading role was played by the the so-called AdS/CFT duality and the underlying integrable structure of it. A far-reaching concept is the effect of boundaries and the corresponding boundary conditions. They are unavoidable in almost all models of mathematical physics and are of the fundamental importance. The introduction of boundaries into the theory of quantum groups leads to a whole new class of the so-called reflection algebras. Such algebras were shown to appear in numerous mathematical models and are at the core of the integrable structure of them. Furthermore, these algebras were also shown to play a prominent role in the AdS/CFT. However a coherent framework for describing such algebras is not known, and many properties of the reflection algebras are still an open question. The goal of this research is to develop new algebraic methods and intradisciplinary connections between the axiomatic theory of algebras and the theory of quantum groups inspired by the integrable structure of the AdS/CFT, in particular by shedding more light on the effects of boundaries and different boundary configurations. The research is driven by applying algebraic objects such as the quantum affine and Yangian algebras to find elegant, exact solutions describing the models that arise from and are inspired by the gauge/gravity dualities.

The bodily fluids of the mammalian organism are in a constant state of flux. Even in the absence of challenges such as dehydration, haemorrhage or starvation, salt and water are constantly being lost as a consequence of normal, obligatory renal excretory functions, and by the processes of respiration and perspiration. The body has two mechanisms that function to control the consumption and the excretion of water and salt, in order to maintain the optimal bodily content required for good health. The first mechanism involves the production by a part of the brain paraventricular nucleus (PVN) of a hormone called vasopressin that tells the kidney to conserve water. The second mechanism is behavioural, and involves the instincts of thirst and salt appetite that emotionally drive the organism to correct its fluid balance. These mechanisms can go wrong resulting in ill-health. For example, disorders of fluid balance are evident in a substantial proportion of elderly patients admitted to hospital, and dehydration is a frequent cause of morbidity and mortality in old people. An age-related decline in the response to a variety of dehydrating challenges has been reported in humans, and this seems to involve a reduction in thirst and salt appetite, as well as dysregulation of vasopressin production. Another way that disorders of fluid balance can affect wellbeing is as a consequence of an excessive intake of dietary sodium, which is associated with the development of several chronic degenerative diseases, such as cardiovascular disorders, including hypertension. These medical conditions, which are becoming more prevalent as a result of increased life expectancy, progressively decrease life quality and increase the need for medical and social assistance. Epidemiological and experimental studies have suggested that events occurring in utero and during lactation can result in long-term consequences in adult life. Interestingly, both excessive salt intake and dehydration during pregnancy provoke increased salt appetite in adult offspring, which may then impact on long-term health and wellbeing. We have recently produced exciting new evidence that suggests that the PVN is not only involved in the production of vasopressin, but also has a central role in generating the instincts that control the consumption of salt. We thus hypothesise: i) that the PVN integrates hormonal and behavioural responses to salt and imbalance. ii) that these integrative functions are perturbed in old age, resulting in decreased thirst perception, reduced sodium appetite, and altered activity of AVP neurones. iii) that these integrative functions are perturbed by foetal exposure to high salt, resulting in a reprogramming of the set point for adult salt consumption. Or aims are now to decipher the molecular mechanisms by which the PVN controls behavioural (thirst and sodium appetite) and hormonal (AVP synthesis and secretion) mechanisms of salt and water homeostasis. Further, we will find out how these mechanisms go wrong in old age and following foetal programming.

A great deal of our acquisition of knowledge is dependent upon the assistance of 'external' factors. For example, it can depend on the use of technology (e.g. your iPhone), or on one's social environment (e.g. when one trusts the word of an expert). Nevertheless, it might be held that knowledge is essentially an 'internal' matter. That is, that while one might make use of external resources when acquiring knowledge, such as instruments (the iPhone) or informants (the expert), whether or not one knows is ultimately just down to the individual and their own 'internal' cognitive resources. It is, after all, the individual who is successfully making use of the instrument, and the individual who makes the decision to rely on the information provided by the expert. While such an 'internalist' account of knowledge has for a long time been central to the theory of knowledge, it has come under pressure in recent years, with the pressure coming from several different quarters. Epistemic externalism holds that factors about which one is completely unaware can have a significant bearing on whether one has knowledge. For example, some epistemic externalists have argued that when one acquires knowledge the belief-forming process used (e.g. one's eyesight) must be in fact reliable, whether or not one is aware that this process is reliable. Content externalism holds that environmental factors can have a bearing on the content of one's mental states (i.e., what those mental states are about). For example, some content externalists have argued that whether one's thoughts are about a particular substance in the world, such as water, can depend on facts about the chemical composition of the substance in question. Consequently, on this view whether one has knowledge that a particular substance is water can depend on facts about one's environment. Extended cognition holds that factors which are outside of one's skin can in certain conditions be genuine constituents of one's cognitive processes. So, for example, if an agent and an instrument are related in the right way, then they can potentially form a 'cognitive whole'. Applied to knowledge, extended cognition holds that, say, one's iPhone can in principle be more than just an 'external' instrumental for acquiring knowledge, for it can be a constitutive part of the very cognitive process by which knowledge is acquired. Distributed cognition holds that in certain conditions--such as in the context of a highly collaborative scientific inquiry--we should think of cognition not at the level of the individual but rather at the level of the group. Applied to knowledge, distributed cognition entails that in certain cases we should collectively ascribe knowledge to a group of agents rather than to the individuals who make up this group. All four proposals present a challenge to the 'internalist' conception of knowledge set out above, since in their different ways they undermine the idea that the acquisition of knowledge is primarily due to the 'internal' cognitive resources of the agent concerned. The purpose of this project is to produce, for the very first time, a systematic exploration of these four different ways in which knowledge can be 'externalised'. On the basis of this systematic exploration we will then offer a detailed investigation of two specific ways in which knowledge can be 'extended' that are of particular significance to contemporary cognitive science: extended cognition and distributed cognition. The project will draw together an international body of researchers, both early career and established. It will result in a world-class body of research output which will transform the contemporary research agenda in epistemology and philosophy of cognitive science. It will also engage with the public and with non-academic partners, through public lectures, an 'impact' workshop, and via a dedicated project webpage and blog.

Pulmonary arterial hypertension (PAH) is a disease that causes raised blood pressure in blood vessels that pick up oxygen from the lungs. It has a life expectancy similar to some advanced, common cancers. There is treatment available but there is no cure. We now know that PAH is associated with weakness in the muscles in the legs, which contributes to the symptoms that patients experience. It is also becoming clear that rehabilitation can improve patients exercise capacity and reverses the changes seen in their muscle cells. These classes can improve quality of life and may prolong people's lives. Researchers believe that certain proteins found in high levels in the blood of patients with other chronic diseases can affect muscle function and growth. One of these proteins is called growth differentiating factor (GDF) 8, high levels of which are associated with muscle weakness in COPD and heart failure (HF). Interestingly there are drugs available which block the actions of GDF-8 on muscle cells which has been shown in animals to result in increased muscle size. A related protein called GDF-15 is found in elevated levels in patients with PAH, and is linked to prognosis. We started investigating the role of GDF-15 in the development of muscle weakness. In patients with COPD as well as healthy volunteers we found that as GDF-15 levels went up, muscle strength went down. We also found that GDF-15 levels in the blood stayed high after heart surgery only in patients who lost more than about 10% of their thigh muscle size. Furthermore we showed that the mechanism through which GDF-15 changes muscle strength and size is the same as that seen in GDF-8. Finally when we added GDF-15 to muscle cells they became smaller. We believe these preliminary results suggest that GDF-15 may be an important protein in causing muscle weakness in PAH and that it may act through the same mechanisms as GDF-8. We aim to test this theory by finding out where GDF-15 is produced and whether it is associated with muscle weakness in animal models of PAH. We want to discover what happens when we add GDF-15 and drugs that may block its actions to muscle cells, and to find out whether GDF-15 levels in the blood and muscles of patients with PAH are involved in the development of muscle weakness The research will be carried out by a PhD student under the supervision of a number of experts in the field of muscle weakness and PAH at Imperial College London. We will take the tissue of rats and mice with pulmonary hypertension and examine where GDF-15 is produced. We will take the muscle tissue of these animals and analyze them to see the whether the levels of these proteins in the muscle is related with weakness. Next we will try and define the effects of these proteins on muscle cells and find out how they cause these effects. We will do this first by adding proteins to growing muscle cells in the lab and then blocking their actions using drugs which may stop GDF-15 binding to these cells. Next we will add genes, which cause increased production of GDF-15 to the muscles of mice. Once we establish that this results in muscle weakness we will try to block their actions by adding further genes which cause release of proteins that stop GDF-15 binding to muscle cells. Finally we will investigate the levels of GDF-15 in the blood of patients with PAH to see whether these are related to muscle weakness. We will also take muscle biopsies from the patients who allow us to, in order that we can examine the way in which GDF-15 may cause muscle weakness in men and women with PAH. We expect this work will lead to a greater understanding of the role of GDF-15 in muscle weakness in patients with PAH. IN addition GDF-15 levels may be important in allowing us to define which patients have muscle weakness. We hope in the future to perform a clinical trial of drugs which block the actions of GDF-15.

To specify and standardise test battery required to examine effects of food ingredients on appetite, mood and cognition. To develop and program a multiple functionality 'App' that can be used to rate satiety, mood and cognitive performance within human intervention studies.

Methane is the second most important greenhouse gas and contributes to the atmospheric chemistry affecting ozone. Southern tropical methane sources and sinks constitute a significant component of the global methane budget. The current major anomaly in southern methane growth rate is among the largest on record. Yet despite its importance, tropical methane variability has received relatively little study. This proposal is to investigate the southern tropical methane budget. The work will improve quantification of southern tropical sources and the understanding of the mechanisms of sudden growth events. Southern tropical methane sources are varied, each having their own isotopic signature in the methane they produce. Wetlands are very extensive in southern tropical S. America and in western parts of southern sub-equatorial Africa, but data on methane emissions from these wetlands are very sparse. Fires in savanna grasslands in Africa and S. America are also significant sources, as are the large ruminant animal populations. Anthropogenic sources are also increasing, with major recent hydrocarbon discoveries. Tropical OH is the major global methane sink. Ascension Is. is a uniquely located, UK-administered, experimental site for studying the methane budget. At surface the air is almost always SE Trade wind, which arrives from the South Atlantic middle latitudes, and, after Ascension, becomes the background air for Amazonia. Above the trade wind inversion, the air over Ascension is tropical, its origin switching regularly between Africa and S. America. Currently Royal Holloway sustains continuous high-precision CH4 and CO2 measurement (CRDS instrument) and also flask measurement of d13C in CH4 on Ascension, as well as on E. Falkland Is. and on RRS JC Ross. Methodologically, the project will focus on the measurement of methane in the southern tropics, carrying out campaign studies, especially on Ascension, and modelling the results. Measurement will include continuous measurement by CRDS in Ascension, E. Falklands, bi-annual Atlantic transects by RRS JC Ross, and Tedlar bag sample collection for CH4 and d13C of CH4 in Uganda, Peru and Bolivia. Campaign studies will include installation of a CRDS instrument in Peru and use of an unmanned aerial system (UAV) to sample above the Trade Wind Inversion on Ascension, as well as source campaigns to characterise d13C signatures of CH4 emissions in Africa and S. America. The proposed helicopter UAV deployment exploits new expertise and would represent an important UK deployment of a substantial UAV for atmospheric sampling. This deployment therefore addresses one of the key science challenges set out in the NERC scoping study for next-generation platforms for Earth & Environmental Science. Modelling studies are also state-of-the-art, and will include regional trajectory analysis to assess source inputs across Africa and S. America, and global modelling of d13C of CH4, tested against the measurements made in the project. The results will be used to assess the importance of southern tropical methane in the global budget, the causes of rapid past changes, and the possibility of future rapid growth in emissions.

In 1911, Noon and Freeman published their account of the treatment of a hay fever sufferer with pollen extract. This was one of the first documented descriptions of specific immunotherapy (SIT) in which the agent causing the allergic condition was used to 'desensitise' the patient. While the value of SIT has been widely accepted, the approach still carries the risk of severe side effects including anaphylactic shock. The investigation of SIT for treatment of autoimmune diseases has lagged behind that of SIT in allergy and has also been hampered by aberrant events. For example, administration of a brain protein exacerbated a disease resembling MS in primates. Similarly, administration of an artificial islet antigen, via the lung or gut, induced T lymphocytes that exacerbated autoimmune diabetes in an animal model. The complications associated with intact antigen have led opinion leaders in the field to recommend the use of fragments of proteins called 'synthetic peptides' for SIT. Our laboratory studies the design and mode of action of peptides that are able to suppress immune responses. Effective induction of suppression depends on the solubility of the peptide. Previously we had shown that some peptides failed to mediate SIT even when administered in a highly soluble form. This proved to be because the peptides could bind to their receptor, an immune molecule called MHC, to produce the wrong shape or conformation. Peptides can be designed, however, to fit the MHC appropriately and these then induce tolerance to the native protein. Effective SIT with peptides leads to the induction of a subset of lymphocytes, known as CD4 T-cells, and they secrete a protein called IL-10. IL-10 is a hormone-like substance, known as a cytokine, that suppresses activation of neighbouring T cells in the body via a negative feedback loop mechanism. It was recently shown that peptide SIT in allergic asthma also generates IL-10-dependent suppression thus revealing a similar role for IL-10 in SIT for both allergy and autoimmune disease. The overall aim of this current proposal is to improve the efficacy of peptide-induced SIT by enhancing the conversion of lymphocytes capable of causing disease into IL-10 secreting disease suppressor cells. Recently we showed that the addition of drugs that block the activity of the enzyme GSK-3 to cultures of lymphocytes in vitro greatly enhanced their production of IL-10. The specific aims of this project are, therefore, to: i. identify the most suitable GSK-3 inhibitor from a panel previously characterised by GSK ii. investigate the ability of GSK-3 inhibitors to enhance the in vivo generation of IL-10 secreting suppressor cells in conjunction with SIT in a relevant animal model of autoimmune disease iii. confirm the activity of the selected inhibitor/s on human lymphocytes iv. assess the stability of the IL-10 phenotype in both mouse and human cells There are no patents relating to these compounds and, as a result, no 'freedom to operate' issues associated with them. We propose a novel application for these compounds, as adjunct treatments, in conjunction with SIT, for immunotherapy of autoimmune diseases and allergies. We have conducted patent searches relating to this application of the drugs and have not found prior art. The enhancement of IL-10 production during SIT will greatly improve the efficacy of this therapeutic approach. As such, the use of GSK-3 inhibitors as adjunct therapy will be applicable to any allergic condition currently treated by SIT or equally to any autoimmune condition for which the target antigens are known. The improvement of SIT provided by co-administration of GSK-3 inhibitors will allow health care providers to move away from the use of non-specific therapies for allergic and autoimmune diseases since these are often ineffective and can cause severe side effects. This improvement will be of considerable benefit to both patients and the health care system.

Future deployments of wireless sensor network (WSN) infrastructures for environmental, industrial or event monitoring are expected to be equipped with energy harvesters (e.g. piezoelectric, thermal or photovoltaic) in order to substantially increase their autonomy and lifetime. However, it is also widely recognized that the existing gap between the sensors' energy availability and the sensors' energy consumption requirements is not likely to close in the near future due to limitations in current energy harvesting (EH) technology, together with the surge in demand for more data-intensive applications. Hence, perpetually operating WSNs are currently impossible to realize for data-intensive applications, as significant (and costly) human intervention is required to replace batteries. With the continuous improvement of energy efficiency representing a major drive in WSN research, the major objective of this research project is to develop transformative sensing mechanisms, which can be used in conjunction with current or upcoming EH capabilities, in order to enable the deployment of energy neutral or nearly energy neutral WSNs with practical network lifetime and data gathering rates up to two orders of magnitude higher than the current state-of-the-art. The theoretical foundations of the proposed research are the emerging paradigms of compressive sensing (CS) and distributed compressive sensing (DCS) as well as energy- and information-optimal data acquisition and transmission protocols. These elements offer the means to tightly couple the energy consumption process to the random nature of the energy harvesting process in a WSN in order to achieve the breakthroughs in network lifetime and data gathering rates. The proposed project brings together a team of theoreticians and experimentalists working in areas of the EPSRC ICT portfolio that have been identified for expansion. This team is well placed to be able to develop, implement and evaluate the novel WSN technology. The consortium also comprises a number of established and early stage companies that clearly view the project as one that will impact their medium and long term product developments and also strengthen their strategic links with world class academic institutions. We anticipate that a successful demonstration of the novel WSN technology will generate significant interest in the machine-to-machine (M2M) and Internet of Things (IoT) industries both in the UK and abroad.

This proposal addresses directly an enhancement of the efficiency, export potential and energy utilization of the UK concrete industry, as cement is the second most used substance on the planet after water and the manufacturing process produces large amounts of CO2 per year. The proposed technology will enable concrete manufacturers to increase the quantities of low carbon cement they use by developing a highly cost-effective continuous, conveyor-based solid-state microwave-based system for the production of low-carbon concretes incorporating higher levels of waste products, with lower energy use and lower carbon footprint, yet retaining high mechanical performance. The significant reduction in the carbon footprint is expected to lead to rapid environmental, social and economic impact and hence market opportunities.

Prostate cancer is the second most common cause of cancer death in the UK. Despite effective treatments like surgery and radiotherapy, prostate cancer can return. When this happens treatment with hormones and chemotherapy are traditionally used to control cancer. Chemotherapy is often used for patients who do not respond to hormonal treatment any longer. Chemotherapy however can cause severe side effects and does not provide a cure. It is obvious that better treatments are needed. Using the bodies own immune system to treat cancer is an interesting option. We and other researchers have found a particular protein on cancer cells, which can activate a patients own immune cells via a receptor called NKG2D in order to kill cancer cells but not healthy cells. We have also seen that cancer patients receiving hormone treatment or chemotherapy for prostate cancer show lower levels of this receptor on their immune cells. However, after treatment with zoledronate, a drug already commonly used to treat cancer spread to bones, an improvement in this receptor level can be seen. These results suggest that perhaps we can influence the interaction between cancer and immune cells via this receptor. Our aim is to investigate this NKG2D receptor in patients with prostate cancer. We will investigate whether this receptor and the way it works varies in patients with low grade (less aggressive) and high grade (more aggressive) prostate cancer. In addition to this we will look at the influence of various prostate cancer treatments (chemotherapy and hormone treatment) on this receptor. Finally we will investigate whether we can improve the function of the immune system in response to the NKG2D receptor. For this research project we will use prostate cancer tissue samples stored in the Prostate Cancer Tissue Bank at King's College London. We will also use blood samples from patients with prostate cancer undergoing treatment with hormone or chemotherapy. Finally we will use cancer cells in the laboratory to carry out some of our experiments. The research will be carried out in Professor Hayday's laboratory on the Guy's Campus of King's College London. Ultimately our results will increase our understanding of prostate cancer and the immune system and could lead to a new form of prostate cancer immune therapy. New treatments with fewer side effects are needed for thousands of men diagnosed with prostate cancer every year. Therefore this research project will be an important contribution.