Combatting antimicrobial resistance is one of the most significant challenges facing our generation. Bacteria are relentlessly developing new resistance mechanisms against clinical antibiotics, making infections much harder to treat. Therefore, there is an urgent need for new antimicrobial compounds and targets. Brevicidine and laterocidine are antimicrobial peptides that have strong activity against multidrug-resistant Gram-negative bacteria, a class of bacteria that are much harder to kill as they have an extra cell membrane. They are even active against Gram-negative organisms resistant to colistin, our current antibiotic of last resort. Therefore these peptides could be excellent antibiotic candidates. However, they are difficult to prepare by chemical synthesis and less stable than other types of cyclic peptides, and the mechanism by which they kill bacteria is not known. This project aims to develop new brevicidine and laterocidine analogues that are more stable, easier to prepare and have enhanced antimicrobial activity. We will also determine how they kill bacteria, which is important knowledge if these peptides are to become antibiotics.

With the growth of the world-wide web (WWW), there has been a corresponding growth in crimes that use the WWW. Specialist law enforcement investigators are ever more frequently required to examine PCs, laptops, mobile phones, sat-navs, and personal digital assistants (PDAs) for look for incriminating (or exonerating) evidence. This has led to a situation where there is a severe shortage of digital forensic examiners with long backlogs of work, leading to even longer delays within the judicial process. At the same time, lawyers are becoming ever more savvy in finding ingenious alternative explanations for the recovered digital evidence which, if accepted by the court, would allow their client to be acquitted. This research project aims to address both these issues. The former issue will be tackled by devising one or more digital forensic triage schemes in which a digital forensic technician filters or screens each digital device for the expected traces of evidence and the 'probative value' or weight of the recovered evidence is accumulated. Only if this accumulated weight of evidence meets one or more prescribed criteria is the device passed on to an experienced forensic investigator for a full digital examination. The latter issue is to be addressed by using the notions of likelihoods and odds to determine how plausible it is that the recovered digital evidence was in fact formed by the process that the prosecution suspects, rather than by some alternative process that the defence might suggest. If the prosecuting authority performs such an analysis it will aid their decision as to whether to go to trial, and if the expert witnesses are armed with this data it will enable them to be more authoritative than previously regarding the strength of the available digital evidence.

Is volcanism capable of causing species to go extinct? We don't know the answer to this question but evidence from rocks provides some intriguing clues. Thus, it has been recognised that all the extinction events of the past 300 million years coincide with major volcanic eruptions. These eruptions consisted of huge flows of basalt, involving 100s or 1000s of cubic kilometres of lava, that quietly oozed from the ground, plus some much more violent eruptions that scattered volcanic ash over great distances. Working out which of these styles of eruption are most closely associated, in time, with the extinctions has proved very difficult because the fossil evidence is usually found far away from where the volcanism occurred. This project will address this problem by studying a unique example of the volcanism-extinction link from 260 million years ago when lavas and ashes were repeatedly erupted into shallow seas in present-day China. The limestones that formed in these seas contain abundant fossils and evidence of a catastrophic extinction. By studying these Chinese rocks it will be possible, for the first time, to study directly both the volcanism and extinction story in the same place. The work will be supplemented with studies of carbon and sulphur isotopes from the limestones which will allow the scientists to determine changes in the state of the oceans during this interval.

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.

Imaging and quantifying blood flow and perfusion are critical to the diagnosis and management of a range of major diseases including coronary heart disease, valvular heart disease, carotid, cerebral and peripheral vascular diseases, cancer, and chronic inflammation, all of which manifest themselves with abnormalities in flow and perfusion. Existing imaging and quantification techniques have numerous limitations. Ultrasound imaging is one of the most widely used clinical imaging methods, offering safety, real-time imaging, low cost and excellent accessibility. Recent advances in ultrafast ultrasound techniques can increase ultrasound imaging speed by up to two orders of magnitude and have resulted in exciting developments in non-contrast enhanced ultrasound applications, including soft tissue elastography, brain functional imaging and cardiac imaging. If combined with advances in contrast enhanced ultrasound (CEUS) using microbubble contrast agents, the ultrafast techniques have the potential to improve the conspicuity of the contrast agent by up to 10 times and greatly extend the field of view or the dynamic range of blood flows that can be tracked through ultrasound; these hitherto unrealised improvements could dramatically impact the ability to image and quantify flow and perfusion. In this project we propose to develop and evaluate novel ultrafast CEUS methodologies and systems for this purpose, building on our extensive research experiences on microbubble contrast agent imaging. They have the potential to become the next generation ultrasound tools for pre-clinical and clinical imaging of blood flow and tissue perfusion, giving unprecedented performance in terms of accuracy, SNR, sensitivity, specificity and resolution.