The transition elements in the periodic table are characterised by the presence of partially filled d-shells. Molecules that contain such a transition element have a complicated electronic structure because it takes very little energy to move an electron from one d-orbital to another. In consequence, the electronic properties of such molecules are not straightforward to study, either theoretically or experimentally.Crystalline copper dichloride, CuCl2.4H20, is a stable, yellow solid. However, on heating, the water of crystallisation is boiled off to leave the triatomic molecule CuCl2 which is a chemically unstable molecule in an open-shell state (a free radical ). Despite its small size, it possesses a complicated electronic structure. Some progress has been made in the last ten years on experimental measurements of its properties by spectroscopic methods. Theoretical calculations of its structure have not given reliable results so far. The electronic structure of CuCl2 is expected to be the simplest of the transition metal dihalides because there is effectively only one unpaired electron (d9 configuration). The spin of this electron has 2 possible orientations relative to the orbital angular momentum in the ground electronic state; as a result, there are two states of different energy, the so-called spin components. All experimental observations of CuCl2 so far have involved the molecule in the lower of these two states; consequently, the energy separation between them is not known. The objective of the present proposal is to measure this splitting. It is important to determine this quantity because:(i) the separation is of interest in its own right because it gives information on the electronic structure of CuCl2,(ii) knowledge of the separation would allow perturbations in higher vibrational levels to be analysed and(ii) an experimental measurement of the splitting gives a benchmark value to guide theoretical calculations of the electronic properties of CuCl2.

The outcomes of many health interventions critically depend on the ability to identify the disease in a timely manner so the most appropriate therapy can be chosen promptly. Consequently, there is an immediate and growing need to develop healthcare technologies for rapid and accurate detection of bio-markers, associated with specific diseases, and/or disease causative agents, such as pathogenic microorganisms. Microfluidics and lab-on-a-chip technology offer a huge potential for the development of next generation fast and ultra-sensitive bio-analytical devices for diagnostic and therapeutic applications. Particle handling operations - including separation, filtration, concentration, trapping and sorting - are ubiquitous in microfluidic diagnostic technologies and can ultimately dictate the speed, accuracy and selectivity of testing devices. An ideal particle handling technique would be fast (high-throughput), selective (i.e. targeting only the particles of interest), easy to integrate into a multifunctional microfluidic device and, most importantly, not reliant on the use of external fields. This proposal aims to introduce an innovative particle manipulation technique to address all these requirements. This research will also demonstrate the proof-of-concept for using this technique to develop fast and sensitive diagnostic testing devices. Rapid filtration, trapping and accumulation of target particles within the cavities of micro-structured surfaces will be achieved in continuous flow settings by harvesting the chemical energy associated with salt contrast generated by parallel multi-component flows. The mechanisms governing the particle dynamics will be investigated through a combination of experimental and numerical techniques. The dependence of trapping and concentration efficiency on particle properties (especially size and surface chemistry) will be elucidated. The output of this study will be an optimally-designed microfluidic platform, through which two in-vitro diagnostic devices will be developed. One device will enable the rapid filtration of cell-like particles (e.g. liposomes) based on their lipid membrane composition which is an important indicator of a cell's state of health. This assay will offer new opportunities for early detection of drug induced cell death and rapid drug pharmacokinetics screening. Another device will enable the fast and ultrasensitive detection of a biomarker indicative of pathological conditions, including atherosclerosis, pancreatitis and some forms of cancers. Synthetic bio-compatible particles will be incubated in a sample solution where the specific interaction with the disease biomarkers will cause i) the fluorescent signal emission from the particle and ii) a change in particle surface chemistry. The latter effect is intended to enable the conversion of the chemical energy - stored in the form of salt contrast - into particle motion. As a result, the biomarker-activated fluorescent particles will be rapidly trapped and accumulated within target regions of the device whereas the non-fluorescent particles will remain unaffected by the presence of the salt. This will enable a massive signal amplification for the diagnostic assay and, consequently, a fast and accurate detection of biomarker concentration in the analysed sample. In summary, this research will lay the foundation for the development of a new family of low-cost, portable bio-analytical devices based on particle filtration and accumulation by solute-driven transport (FAST) for diagnostic and therapeutic applications. These innovative and highly-sensitive diagnostic tools will enable clinicians to perform rapid and accurate diagnosis and, hence, make timely and informed clinical treatment decisions which are more likely to lead to successful health outcomes.

Abstract from the Case for Support document (section 2):This research project is centred upon the parallel construction, development, and use of two complimentary experimental systems to study processes induced by ionisation in irradiated biomolecular systems. The principle objective is to compare the effects of irradiating a specific target molecule within a cluster with the case of the molecule in isolation. In addition to their fundamental interest in molecular and statistical physics, these experiments will help to bridge the complexity gap between the current understanding of radiation effects in the gas phase and in an absorbing biological medium. This represents a major current research challenge for physicists, chemists, and biologists, with important applications in quantifying the effects of exposure to different types of radiation during cancer therapies.The first experimental system is a versatile and mobile source for hydrated DNA base clusters, proposed for construction at the Open University. During the three year programme, this source will be used to carry out 2- and 1-photon electronic excitation experiments to probe the effects of solvated water molecules upon the valence and Rydberg energy states of key biomolecules and the associated dissociation pathways. The second experimental system, located at the Nuclear Physics Institute of Lyon, will enable a detailed study to be carried out on collisions between fast protons and mass-selected cluster ions comprising DNA bases and water molecules. The major technical challenge in this part of the project is the development of a multi-coincidence detection system for the characterisation of ionisation showers, electron emission, and free radical production induced by proton-cluster collisions. These inter-molecular processes are believed to play important roles in radiation damage to living material.

Radiotherapy kills cancerous cells by repeatedly targeting a tumour with high energy radiation. Although image assisted pre-treatment planning based on CT is performed to minimise the amount of healthy tissues being irradiated, the planned treatment is delivered in a manner that is effectively blind, because there is no monitoring of the patient motion and internal anatomy during radiation treatment delivery and no, dynamically modelled, consideration of possible body change during treatment period. This uncomfortable state of affairs persists worldwide, despite complex new treatments and image guided radiotherapy (IGRT) which members of the consortium helped to develop. Furthermore, there is a concern on the additional imaging radiation dose to the patient from the IGRT. Hence, the MEGURATH project was proposed to introduce metrology guided radiotherapy (MGRT), where the patient is measured, imaged and modelled during treatment delivery via optical sensing to provide non-invasive, radiation-free, real-time 3D patient position monitoring, and dynamic deformation modelling to determine the internal anatomical changes. The project is considered as a significant one with a leap forward approach for a grand challenge, and has attracted interest from Elekta Oncology Systems, Philips Medical Systems, VisionRT and NHS-IP.The MEGRATH programme consists of not only comprehensive research activities with diverse theoretical topics, but also translation of science and technology to the first purpose built IGRT research facility in the UK at the Christie Hospital, and the support of clinical studies selected from breast, lung, bowel, prostate and bladder cancers. The project is expected to make a world class contribution to radiotherapy by increasing our understanding of tumour target and organ at risk behaviour, treatment delivery and control of their impact on cure and complications. The marriage of anatomical modelling and dynamic 3D measurement on demand 'in-treatment', using light rather than ionising radiation like X-rays, will offer the opportunity to gain the pole position in engineering and computational science for oncology. The Collaborating for Success through People call is a valuable opportunity to support, complement, utilise and extend the MEGURATH project, thereby enabling the consortium to maintain, defend and widen its lead.The proposed programme of people-based activities starts with exploratory mutual visits by the PIs and group leaders for exchange of knowledge, creation of ideas and development of active collaboration, followed by two-way investigative short visits and relatively long research visits by researchers for synergistic development, cross application and performance evaluation of promising approaches, and finished by a workshop to provide a venue for the consortium to lead the development of a joint EU project proposal with the participating partners. To provide significant added value to the MEGURATH project in terms of scientific knowledge and new clinical applications, 7 eminent research groups and 1 leading 3D equipment company are selected for participation in the proposed people-based activities:-Two from Poland: Telemedicine Group from AGH University of Science and Technology, and Department of Scientific Information from Jagiellonian University Collegium Medicum;-Three from France: one from the French National Institute for Research in Computer Science and Control (INRIA), and the other two from National Centre for Scientific Research (CRNS), namely, Lyon Research Centre for Images and Intelligent Information Systems (LIRIS) and Signal and Image Processing Research Laboratory (ETIS);-One from Germany: Institute for Electronics Signal Processing and Communications (IESK) at Otto von Guericke Universitt Magdeburg; -One from Italy: Signals and Images Laboratory from the National Research Council (CNR); and-3dMD with the company headquarters in the USA.

We propose a large-scale, multi-faceted, international programme of research on the functioning of the Earth system at a key juncture in its history - the Early Jurassic. At that time the planet was subject to distinctive tectonic, magmatic, and solar system orbital forcing, and fundamental aspects of the modern biosphere were becoming established in the aftermath of the end-Permian and end-Triassic mass extinctions. Breakup of the supercontinent Pangaea was accompanied by creation of seaways, emplacement of large igneous provinces, and occurrence of biogeochemical disturbances, including the largest magnitude perturbation of the carbon-cycle in the last 200 Myr, at the same time as oceans became oxygen deficient. Continued environmental perturbation played a role in the recovery from the end-Triassic mass extinction, in the rise of modern phytoplankton, in preventing recovery of the pre-existing marine fauna, and in catalysing a 'Mesozoic Marine Revolution'. However, existing knowledge is based on scattered and discontinuous stratigraphic datasets, meaning that correlation errors (i.e. mismatch between datasets from different locations) confound attempts to infer temporal trends and causal relationships, leaving us without a quantitative process-based understanding of Early Jurassic Earth system dynamics. This proposal aims to address this fundamental gap in knowledge via a combined observational and modelling approach, based on a stratigraphic 'master record' accurately pinned to a robust geological timescale, integrated with an accurate palaeoclimatic, palaeoceanographic and biogeochemical modelling framework. The project has already received $1.5M from the International Continental Drilling Programme towards drilling a deep borehole at Mochras, West Wales, to recover a new 1.3-km-long core, representing an exceptionally expanded and complete 27 My sedimentary archive of Early Jurassic Earth history. This core will allow investigation of the Earth system at a scale and resolution hitherto only attempted for the last 65 million years (i.e. archive sedimentation rate = 5 cm/ky or 20 y/mm). We will use the new record together with existing data and an integrative modelling approach to produce a step-change in understanding of Jurassic time scale and Earth system dynamics. In addition to order of magnitude improvements in timescale precision, we will: distinguish astronomically forced from non-astronomically forced changes in the palaeoenvironment; use coupled atmosphere-ocean general circulation models to understand controls on the climate system and ocean circulation regime; understand the history of relationships between astronomically forced cyclic variation in environmental parameters at timescales ranging from 20 kyr to 8 Myr, and link to specific aspects of forcing relating to solar energy received; use estimated rates and timing of environmental change to test postulated forcing mechanisms, especially from known geological events; constrain the sequence of triggers and feedbacks that control the initiation, evolution, and recovery from the carbon cycle perturbation events, and; use Earth system models to test hypotheses for the origins 'icehouse' conditions. Thirty six project partners from 13 countries substantially augment and extend the UK-based research.