The Large Hadron Collider (LHC) has allowed us to make measurements of high energy particle interactions with unprecedented accuracy. Recently, previously unexplored particle masses and decays are being measured with such high precision that they are starting to show signs of disagreement with predictions from the Standard Model (SM) of particle physics. As the precision of experimental results from the LHC continues to improve, and new measurements are made, the precision of the corresponding SM predictions will need to be improved as well in order to provide a stringent test of the theory. However, many previous and current SM predictions rely on approximations which are not expected to be valid at the precision the LHC is starting to reach. Moreover, many of these decays involve composite particles; hadrons made up of two or three elementary particles called quarks. Studying these from first principles, without approximations, requires a special computational technique known as lattice quantum chromodynamics (lattice QCD). In lattice QCD, the continuous space-time of the SM is discretised onto a grid or "lattice", with quarks living on the points and gluons, the particles which carry force between the quarks, living on the lines connecting the points. The physics of the quarks can then be studied using lattices with different edge lengths (or "lattice spacings") in order to obtain results in the continuum limit at which the lattice spacing goes to zero. This technique requires the use of large supercomputing facilities, and has worked very well for studying the physics of lighter quarks, such as up, down, strange or charm quarks. Many of the signs of disagreement with theory, and hints of new physics beyond the SM, seen at the LHC are in the physics of bottom quarks. These are much heavier than up, down, strange or charm quarks and require the use of lattices with a very small lattice spacing. This is in turn much more computationally expensive and, until only very recently, doing these calculations without additional approximations remained intractable. However, advances that I have made allow for the high precision study of bottom quark decays using lattice QCD, reaching the level of accuracy required for comparison to projected LHC measurements. Utilising the new upgrade to the UK's STFC high performance computing resources, DiRAC-3, the first objective of my project is to apply these new, state of the art techniques to six different, but complementary bottom quark decays. These decays are under intense ongoing scrutiny by the experimental and theoretical physics community with upcoming measurements at the LHC. I will analyse my results for these decays, incorporating the results from the LHC, searching for hints of new physics and providing a guide for possible future measurements. The second focus of my project is the study of bottom quarks appearing in exotic particles known as "tetraquarks". These are composite particles with four quarks rather than the normal two or three that we see predominantly in nature. The LHC experiment has very recently observed both a four-charm tetraquark and a one-charm tetraquark, while a two-charm tetraquark was observed back in 2003 by the Belle experiment. It has become clear that observations of other types of tetraquark are likely to be made in the future, with compelling theoretical arguments for the existence of tetraquarks with two bottom quarks. However these have not yet been observed, no precise theoretical predictions for their masses have been made, and, furthermore, their internal structure is currently completely unknown. My aim is to make high precision predictions for the masses of these states, as well as to study their internal structure using a novel method of adding electric charge to lattice simulations.

The intestine has a surface area nearly two hundred times greater than the skin, and is exposed to many pathogenic micro-organisms. It requires an effective immune response to protect it from infections. On the other hand, immune responses must not be made against the harmless bacteria and food proteins that are also present. When they occur, these inappropriate responses have serious consequences, leading to inflammatory bowel diseases or food allergies. To ensure our health, the balance between ?immunity? and ?tolerance? must be maintained. A critical cell for maintaining this balance is the dendritic cell (DC). DCs migrate continually, in lymph, carrying information about the intestine to the immune cells in the mesenteric lymph nodes (MLN). On reaching the MLN, DCs interact with T lymphocytes. This interaction is thought to control whether immunity or tolerance will occur. Understanding how DCs control these processes is likely to be highly beneficial in the design of oral vaccines or prevention of inflammatory bowel diseases. However, study of migrating DCs has been difficult because they cannot easily be separated from other cells in the MLNs. The only way to collect cells which are certain to be migrating DCs is by surgery, which is used to collect the DC-containing lymph. Previously this surgery has only been possible in large animals. We have developed humane surgical techniques to collect migrating DCs from mice, and to return them to the MLNs. This will enable us, for the first time, to study these cells and their interactions with T cells, using the sophisticated immunological techniques and resources that are only available in mice. We are currently the only group in the world able to collect migrating DCs from mouse lymph. We believe that the study of these cells will generate important information about how immune responses are controlled.

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Acute Kidney Injury (AKI) as a severe complication in hospitalized patients, a life-threatening complication that still has a high mortality. In addition, AKI is associated with high costs for intensive and prolongued treatment. To date, no early detection of AKI is possible. However, early detection is essential to initiate appropriate treatment, thereby preventing development of disease, or at least reducing the severity. Such an appproach would reduce mortality, and also costs. The proposal aims at developing a technology platform that enables early detection of AKI, based on specific proteins an peptides in urine, so-called biomarkers. These biomarkers have already been identified. For their efficient clinical application a plattform that allows accurate and fast analysis has to be developed, this development is the scope of the project. Upon successful completion of the project, a robust technology will be available that enables early detection of AKI, hence initiation of appropriate early therapeutic measures. We anticipate that as a result of this project, mortality due to AKI can be significantly decreased, and costs can be reduced.