HIV/AIDS is one of the leading cause of mortality globally and the leading cause among women aged 15-44 years. African women aged 15-24 are twice more likely to be infected with HIV than their male counterparts. In Cameroon, one of the countries with the highest gender disparity in HIV globally, adolescent girls are five times more likely to be infected with HIV than boys of the same age. There is a growing number of studies showing that risks taken during transactional sex and commercial sex -in addition to biological susceptibility- are responsible for gender inequalities in HIV/AIDS. However, there is superficial understanding of the main causes driving risky sexual behaviours of women who engage in those practises in Africa. Recent studies have shown that women mainly adopt risky sexual behaviours in order to cope with negative income shocks (e.g. agricultural and climatic shocks, illness or death of family members) and suggest that economic shocks are a substantial piece of the HIV puzzle in Africa. If women adopt risky sexual behaviours to cope with negative income shocks, hence providing women formal risk-coping strategies could be a very promising approach to prevent HIV. However, there are still important gaps in knowledge, mainly because no previous study has been designed to specifically answer this research question. The goal of this research is to fill these gaps in knowledge in order to inform the design of novel public health interventions to tackle sexually transmitted infections (STIs) and HIV. Specifically, the study aims (1) to estimate the effect of economic shocks affecting households on sexual behaviours and STI and HIV acquisition of young women, (2) to identify the channels through which economic shocks affect STIs and HIV, (3) to estimate the effectiveness of an intervention that protects women from economic shocks to prevent STI and HIV and (4) to measure the cost-effectiveness of an intervention that protects women from economic shocks to prevent HIV in the general population. The proposed study will use data from a new cohort of women in Cameroon. The study has recruited 1,500 unmarried women engaging in transactional sex or commercial sex, including three biobehavioural and socioeconomic surveys. A randomised controlled trial was embedded to the cohort study and has provided women allocated to the treatment group with a formal risk-coping strategy (a family health insurance). This research is of immediate necessity to address a vital public health challenge of our time and has the strong potential to have a long lasting impact on shaping the research agenda on HIV/AIDS.

This research project uses a novel methodological approach to determine where mineral dehydration reactions can trigger failure in deforming rocks. This link between dehydration and failure is important at convergent plate boundaries. Where plates collide, the shallow portions of the Earth's crust are affected by so-called thin-skinned tectonics. There, dehydration reactions enable the emplacement of tectonic nappes, which shape mountain belts such as the Swiss Jura, or the Appalachians in the US. Plate collision also leads to the subduction of tectonic plates, where dehydration reactions are suspected to trigger seismic events at depths of several tens of kilometers. In both tectonic settings hydrous minerals in rocks become unstable as temperature increases. They start to transform into denser minerals by releasing water in dehydration reactions. The density increase produces pores, which are filled by the water. The pores, the fluid pressure in them, and the newly grown minerals weaken the reacting rock mechanically. It may become unable to support tectonic stresses and fail. The processes that control large-scale tectonics start at the grain scale. These grain scale processes entail a series of complicated, intertwined developments that involve the chemistry, hydraulics and mechanics of a dehydrating rock. Coupled chemical, hydraulic and mechanical processes may facilitate the self-organization of the dehydrating rock into a state where it ultimately fails. Unfortunately, neither classical laboratory experiments nor field-based studies allow a spatial and temporal (4D) characterization of these coupled processes on the micro-scale. Models to explain failure in dehydrating rocks therefore lack a robust observational basis. We will use a unique combination of new methods to overcome this severe limitation. Our interdisciplinary team of experienced researchers will establish a technique to directly observe dehydration reactions in deforming rocks. We will employ the most powerful x-ray sources in the UK and Switzerland to observe dehydration reactions in a new generation of experimental pressure vessels. These vessels are transparent to x-rays and allow us to reproduce conditions at the base of tectonic nappes and at intermediate depths in subduction zones. They are designed and built in Edinburgh. Combining these vessels with time-resolved (4D) x-ray microtomography will enable us to document mineral dehydration at a wide range of conditions. The resulting 4D microtomography data sets will have a volume of several tens of TB. New analysis techniques based on machine learning will allow us to extract the relevant information from these vast quantities of data. Our analyses will determine conditions where dehydration causes rocks to become unable to support tectonic stresses. Using these analyses, we will test and advance theoretical concepts used to link dehydration and deformation in numerical simulations. The first direct observation of the complex grain-scale developments during dehydration reactions will significantly advance our understanding of some key processes in tectonics. Because our data are time-resolved and dynamic, they will support the interpretation of field data that otherwise capture a static, fossilized picture of dehydration reactions. Our data will allow testing and refining existing mathematical models that provide a foundation for robust simulations of large-scale tectonic processes. Ultimately, our findings will support the assessment of risks associated with plate collision. Our project will also make a new experimental imaging method available for research on geothermal energy, CO2 sequestration and nuclear waste storage. The method combines time-resolved x-ray microtomography in our new experimental vessels with advanced data mining and image analysis and computational simulation.

Epithelia are layers of cells that cover body surfaces and line internal organs. They form functional barriers that protect us from the environment and enable our organs to generate and maintain compartments of different compositions, such as the barrier that separates the retina from the blood at the back or the eye. For individual epithelial cells to interact and form epithelial tissues, they need to assemble adhesive complexes with neighbouring cells. One of these adhesive complexes is called tight junction and forms a barrier in between neighbouring cells; hence, tight junctions are essential for epithelia to form tissue barriers as they prevent random diffusion along the space in between neighbouring cells. Consequently, the integrity of tight junctions must be maintained in order to prevent epithelial barrier breakdown and tissue failure. However, epithelial cells are often under physical strain and undergo cell shape changes during cell division or during the development of our organs and tissues. Therefore, mechanisms are likely to exist that allow tight junctions to adapt to changing cell shapes and, possibly, help cells sense and adapt to external physical forces that act on tight junctions. Here, we focus on the questions of whether such mechanisms exist and how such molecular bridges are built. Tight junctions are composed of many different proteins that form a molecular network that starts with cell-cell adhesion proteins at the cell surface by which cells interact with each other. These cell-cell adhesion proteins interact with a large range of proteins inside the cells that regulate the various junctional functions and that are thought to function as molecular scaffolds that support the structure of tight junctions. Some of these proteins can also interact with the cytoskeleton, a network of protein fibres that supports the cell's structure and shape. However, the functional relevance of these interactions is not well understood. We hypothesized that components that can interact with the cell-cell adhesion proteins at the cell surface and the internal cytoskeleton might work as force transducing linkers. Hence, we have constructed a sensor based on such a protein that allows us to determine whether the molecule is indeed under tension. Pilot experiments indicate that the sensor is functional and that tight junctions are indeed a force-bearing structure. Our objectives now are to determine the junctional architectural principles that enable tight junctions to bear forces and transduce them between the cytoskeleton and the cell surface, and to make use of functional assays to determine the physiological function of these principles for epithelial tissue formation and development. The expected results will help us to understand physiologically important processes relevant for organism development, and tissue function and regeneration. They will contribute to our understanding of common diseases that disrupt epithelial tissues such as cancer, viral and bacterial infections, and common chronic inflammatory and age-related conditions. We also expect that the results and principles to be discovered will support tissue engineering and regenerative medicine approaches.

Catastrophic failure is a critically-important phenomenon in the brittle Earth on a variety of scales, from human-induced seismicity to natural landslides, volcanic eruptions and earthquakes. It is invariably associated with the structural concentration of damage in the form of smaller faults and fractures on localised zones of deformation, eventually resulting in system-sized brittle failure along a distinct and emergent fault plane. However, the process of localisation is not well understood - smaller cracks spontaneously self-organise along the incipient fault plane, often immediately before failure, but the precise mechanisms involved have yet to be determined. Many questions remain, including : Q1 - How do cracks, pores and grain boundaries interact locally with the applied stress field to cause catastrophic failure to occur at a specific place, orientation and time?; Q2 what dictates the relative importance of quasi-static and dynamic processes?; and Q3 - why can we detect precursors to catastrophic failure only in some cases? Here we will address these questions directly by imaging the whole localisation process, using a newly-developed x-ray transparent deformation cell and fast synchrotron x-ray micro-tomography. We will visualise the nature and evolution of the localisation process structurally and seismically together for the first time at high resolution in a synchrotron. We will deliberately slow the process to image its evolution, and to investigate the strain-rate dependence of the underlying mechanisms, using rapid electronic monitoring and feedback control. This will provide unprecedented direct observation of the relevant mechanisms, including the contribution of seismic (local cracking producing acoustic emissions) and aseismic (elastic loading and silent irreversible damage) processes to the outcome. This innovative combination of techniques is timely, feasible, and is likely to transform our understanding of the role of microscopic processes in controlling system-size failure. The results will provide interpretive models for similar processes in natural and human-induced seismicity, including scale-model tests of strategies for managing the risk of large induced events.

All cells are covered in a forest of diverse carbohydrates structures known as the glycocalyx. There are many types of cell-surface carbohydrates (glycans) - some are long linear polymer chains, while others have short highly branched architectures like small trees. The composition of the glycocalyx is different for different types of cells - while the range of glycan structures present can be similar, the relative quantities of each glycan can vary considerably from one type of cell to another. Glycocalyx composition also changes if a cell becomes cancerous, and so measuring the composition of a glycocalyx presents opportunities for cancer diagnosis. Currently, the only way to measure how much of each type of glycan is present on a cell is to chop them off the cell, and weigh them individually in a mass spectrometer. The aim of this research project is to develop molecular tools that can be used to quantify how much of a particular glycan is present on an intact cell surface, and to bind with high selectivity to cells that have a particular glycan composition. These probes will have applications in understanding biological processes, and could ultimately be used as medical diagnostics and for targeted delivery of drugs to specific cell types. So how do you differentiate between two cells that have the same set of cell surface molecules, and differ only in the relative abundance of those molecules? Traditional probes like antibodies usually bind with high affinity to only one or two copies of their target molecule. They can be used to tell if a specific type of molecule is present on a cell surface, but not to bind selectively in response to a specific density of their target molecules. Density-dependent 'superselective' binding requires a different strategy that is inspired by glycobiology - the biology of carbohydrates. Carbohydrate-binding proteins often interact relatively weakly with their target glycan and strong interactions are achieved by having many copies of the glycans and glycan-binding proteins interacting with one another in concert - so-called multivalent binding. In this way, many weak interactions come together to enhance binding strength, but it also greatly enhances the selectivity of binding. Here we will develop multivalent probes that can bind in a density-dependent manner to cell surface glycans. We will develop probes that can distinguish between cancerous and healthy cells, and probes that can be used to map out complex net-like glycocalyces that regulate the function of neuronal cells. The methods developed will have much broader application for highly specific binding to target cells in both biology and medicine.