Since the discovery of the carbonised papyri at Herculaneum in the 18th century, there has been a great deal of interest in accessing the content contained in the scrolls preserved by the intense heat from the eruption of Mount Vesuvius in 79 CE. The first attempts to open these scrolls were made by hand using a knife, but this caused them to break into fragmented chunks. Subsequently in 1756 a machine was invented to create a safer method of unrolling, which was more successfully applied to numerous scrolls. However, in many cases it was impossible to keep the different layers of papyrus from sticking to each other, and so substantial portions of text remained hidden in even successfully opened scrolls, while hundreds of scrolls remained too firmly carbonised to unroll at all. The content of these fully intact scrolls, together with that of text under the stuck-on layers remains a mystery. New technology offers a solution. In the early 21st century the application of non-invasive CT scanning, a concept already proved by project members, reveals new possibilities. The structure of a scroll can be rendered digitally in three dimensions, revealing the layers of the papyrus in the scroll's circumference. Computational methods for algorithmically separating, unrolling, and flattening these layers have been developed by project members over the past decade. The virtual unrolling method has been successfully applied to P. Herc. 375 and 495. Nevertheless, despite such an achievement, the ink does not appear with any significant clarity. And while faint traces of a handful of Greek letters have been transcribed, there is currently no means to verify and replicate such results. This project aims to address the problem of detecting ink in this non-invasive imaging and thus definitively solve the long-standing problem posed by the Herculaneum papyri. In 2016 project members successfully applied the virtual unrolling method to a carbonised Hebrew scroll from the site of Ein Gedi in Israel. The ink was immediately visible, but this was due to the fact that it was contaminated with heavy trace elements and thus naturally appeared in CT scanning. The carbon-based ink used in Herculaneum papyri cannot be visualised in the same way. However, we now know that the ink is weakly contaminated with lead. We thus propose a new method called Dark Field X-ray Imaging. This reveals ink by isolating and capturing trace elements, such as lead, in its composition. To enhance the resulting ink signal further we introduce a new neural network called Reference-Amplified Computed Tomography (RACT) to amplify both the ink's presence and the shapes of the Greek characters for improved legibility. This method will definitively solve the problem of reading the text hidden in the Herculaneum papyri. To add value, the project will make the data generated by this process accessible to researchers and the curators responsible for these artefacts, by developing a new digital platform, the Augmented Language Interface for Cultural Engagement (ALICE), ensuring that the data produced by the Dark Field X-ray Imaging and RACT processes is accessible, can be properly curated, and that the extracted text can be digitally edited. Moreover, ALICE includes the functionality for integrating 3D models of the original artefact and for recording the metadata that explains both how the text was created and from where in the object's geometry the text originates in the model generated along with its digital edition. This is necessary for scientifically verifying and replicating any subsequent analysis or publication of the data. Significantly, for other cultural heritage artefacts that contain hidden text, our new imaging techniques and digital platform will be built using open architecture standards; the source code will be easily adaptable for non-invasive reading of writing inside other intractable artefacts, such as burnt books, book-bindings, and mummy cartonnage.

When we think about spacecraft we tend to refer to planets' exploration, but most of the every-day electrical items we normally use (TV, mobile phone, sat-nav etc.) also use satellites and they require more and more sophisticated technologies. The construction of spacecraft is a very long and complex procedure, which needs to be maintained in line with the development of technologies on Earth. There is the need to make this process faster and more affordable. In the development of a satellite two factors that significantly affect cost and duration of the process are the design of the spacecraft for MAIT (Manufacturing, Assembly, Integration and Test), and the long testing process the spacecraft has to undergo (structural, thermal, electrical and optical) with all the uncertainties related to it. For both issues a novel approach for space applications, virtual testing, would tackle both issues. The final aim of this research is to develop an end-to-end digital model which would virtually reproduce all the test facilities into one single umbrella software where the computational model of the spacecraft can be "tested". Doing this before the real test would give the manufacturer company the real scenario their spacecraft will undergo during test without any unexpected turnout. This, on one side, allows an ideal design in terms of cost/efficiency compromise, and, on the other side, prepares the company on all the possible issues during the test phase, which can be promptly corrected for a smoother physical test procedure. The research is split into three stages: i) building on the expertise gained in the last 2.5 years as postdoc working on virtual testing for vibration tests, the virtual model will be further developed and refined for all possible industry implementations (e.g. correlation of the finite element model, replacement of specific vibration test processes for drastic reduction of over-testing); ii) following the same guidelines developed for vibration tests, virtual models will be built for thermal, electrical and optical tests (comparing virtual results to real test scenarios and nominal analyses); iii) all the virtual models will be collated to develop the final end-to-end digital model (with production of guidelines for use). The final product outcome of the research will be a tool beneficial to multiple entities: clearly test facilities, which can provide an extra service to manufacturer companies before performing the real tests on the spacecraft; small companies which would take advantage of the significant amount of savings in terms of time and cost for accessing a more affordable market; research and development sector, which can take advantage of the virtual models built for the different test facilities and investigate the possible modifications to the current procedures, same as this research is doing for structural tests.

The determination of chemical structure is vital in understanding the efficacy of medicines and materials and consequently underlies innovation. The equilibrium positions of atomic nuclei can be routinely determined by the technique of X-ray diffraction. However, this provides only part of the information required by a chemist. In order to develop new medicines and materials it is necessary to understand bonding character and reactivity; these are determined by the energies and spatial distributions of electrons, the so-called "electronic structure". In order to investigate electronic structure, including the changes it undergoes during a chemical reaction, new probes are required. Whereas photoelectron spectroscopy (the emission of electrons caused by the interaction of molecules with UV light) has long been known to be sensitive to electronic structure, far more intimate details can be obtained by the measurement and analysis of the angles through which the photoelectrons are emitted. The information content of these angular measurements dramatically improves if measurements can be made relative to bonds in individual molecules. This is challenging because free molecules rotate, and measurements are therefore averaged over all the possible molecular orientations. Furthermore, a full characterization requires measurements to be made over a wide energy range. The combination of these requirements has severely limited the scope of most experiments to date. The recent parallel developments of (a) techniques to align molecules in space, and (b) technologies that have enabled the development of a new generation of high energy light sources, is set to revolutionize capabilities, bringing the exciting prospect of observing how electronic structure evolves in time. Here, we propose a series of novel experiments that will combine and exploit these ideas and technologies to develop sensitive probes of evolving electronic structure, and protocols for their implementation and interpretation, facilitating uptake by other groups. The proposed work is timely because of the recent technological developments and the research team is well-placed to advance the state-of-the-art through their expertise in the measurement and interpretation of photoelectron angular distributions and in light source development.

Cancer treatments have undergone three revolutionary stages over the past few decades: chemotherapies, biomarkers targeted at mutated genes, and combined treatments of biomarker targeting and immune process mediation. Each stage of these treatments was facilitated by advances in our understanding of the behaviour of cancers, especially at the molecular and cell levels. Our early understanding of the high growth rates of cancerous cells led to the development of chemical/drug therapies together with radiation treatments to kill cancerous cells. However, such medical treatments must undergo rigorous clinical trials and meet regulatory requirements, e.g., FDA approval, before clinical deployment. This process plus further improvement to perfect the treatments can take more than a decade. Currently, chemotherapy is still the mainstream cancer treatment for patients, but their toxicity remains a major limiting factor to survival rates. Over the past 5-8 years, the ability to moderate immune processes has been realised, and a number of pioneering treatments based on this new line of thinking have very recently achieved clinical success. This prospect has driven a major global effort to develop new treatments based on antibody technologies, covering not only oncology but also other major diseases including cardiovascular, respiratory, autoimmunity and infectious diseases. Antibodies used for cancer or other disease treatments must be designed, manufactured, separated, purified and eventually formulated into medical products ready for clinical use. A popular means of administration is to apply via intravenous injection. This option requires the antibody drugs to be formulated as a stable protein solution in a bottle (glass or plastic) or a ready-to-inject syringe set, with a shelf-life between 1-2 years. Because these bioengineered antibodies have to be equipped with two or more biological functions, their amino acid sequences (so called primary sequences) must be altered. As a result, we do not know how stable their folded domains are and how instability from the modified domains will affect the stability of the whole antibody. All proteins are amphiphilic due to the presence of both polar and apolar amino acids on their surfaces. This amphiphilic character drives proteins to adsorb and desorb at different interfaces spontaneously. During these interfacial processes, proteins interact with the substrate surface and with themselves, and depending on the nature of the substrate surface and the close proximity between them once adsorbed, deformation of the globular structures and even local unfolding can occur, causing exposure of hydrophobic patches that may induce aggregation and precipitation, compromising the bioactivity of such antibody drugs. Newly bioengineered antibodies are often unstable, and adsorption can accelerate their instability. Using a series of bioengineered antibodies with well-controlled sequence modifications in Fab and Fc domains, this LINK project forges a new collaborative team involving MedImmune, Manchester University and Imperial College London, with the aim to develop new understanding by combining neutron reflection experiments with molecular dynamics simulation. We will examine how certain well-controlled sequence modifications in Fab and Fc domains affect their adsorbed globular structures and how instability in these domains affects the structure of the whole mAb. Another line of work will be to examine how representative substrate surfaces affect structural deformation and unfolding. These studies will lead to new results that will be of great value to the biopharmaceutical industry and to academic research. The successful delivery of this project will lead to new primary structure-stability relationships that will assist MedImmune and other protein drug developers to improve their antibody stability in their biotherapeutics. The outcome will ultimately benefit the general public.

Space technologies, data and services have become indispensable in our everyday lives. Communications satellites (COMSATs), alongside optical fibre, are the main means of global data transmission. In fact, for a vast number of users, such as marine and airways fleets, autonomous cars, remotely located aid camps, and hospitals and schools in less developed areas, satellite communication is the only way to broadcast, navigate or access broadband services. Earth observation satellites provide immediate information in the event of natural disasters, and allow better coordination of emergency and rescue teams. Satellite-based technologies help increase the efficiency of fisheries and agriculture, and play an important role in transport by controlling air and maritime traffic. Both COMSAT and surveying services are critically dependent on the communication links between satellites in orbit and ground control stations. Increasing data capacity of these links and allowing frequency flexibility, which cannot be easily provided by established RF solutions, is long overdue. It is clear that industry needs a step change in technology. Against this backdrop, the project focuses on using key advances in photonic integrated solutions to revolutionise satellite payloads (modules). An integrated photonics approach allows for several optoelectronic functionalities (lasers, photodiodes, etc.) to be monolithically integrated on a single chip. Such integration improves robustness, reduces losses between individual devices and, most importantly, offers ease of scalability, low mass and small footprint, creating great prospects to reduce the cost of satellites. Through close collaboration with academic and industrial partners, this project will develop the world's first integrated, broadly tuneable, photonic-based Frequency Generation Unit (FGU) which can be the heart of satellite communication payloads. The advantage of a photonic FGU over the conventional RF-based solution comes from the great frequency agility of the photonic system, which will allow for the FGU to be included both in communication and earth observation satellites. Firstly, the FGU will form part of innovative communication payloads in communication satellites (transponders), allowing for high-throughput data links from satellites to ground stations and, in the future, between satellites. Furthermore, the FGU will also be deployed in earth observation satellites, allowing for reference-signal distribution inside the satellite using a flexible, lightweight optical fibre rather than a conventional coaxial cable. The use of a photonic FGU would dramatically reduce the weight of a satellite, eliminating the need for tens to hundreds of kilograms of coaxial cables (depending on satellite type), and make a significant monetary saving, given the cost of launching into orbit of $25,000/kg. Secondly, a novel architecture for a complete communications payload based almost entirely on photonics is going to be investigated. Replacing conventional RF components with integrated photonic sub-systems will result in an unprecedented mass and volume reduction, which, in turn, will lead to a reduction in the cost of in-orbit-delivered data capacity.