In many distributed computing contexts, a need arises for two mutually-distrusting parties to undertake a joint calculation, often without the disclosure of the unprocessed data from one or both sides to the other. Sometimes a 'trusted third party' is used for this purpose - but immediately the verification of the trustworthiness of that party becomes a challenge. The cryptographic world has addressed this through the paradigm of secure multi-party computation - and the related problem of an untrusted processor through various schemes of homomorphic encryption. These are successful in many contexts, but imply certain overheads and complexities. We propose a different model, wherein the technologies of Trusted Computing are used to create an assured Trustworthy Remote Entity (TRE): this also enables us to develop duplex communications, which are seldom considered in the approaches described above. The main part of this project is devoted to developing and verifying a TRE-based solution for the substantial and far-reaching challenges of security and privacy in smart power grids: later in the project we consider the generalization of the approach to other similar problems, such as those in dynamic location-based road pricing. The 'big idea' is that the user can be signed up with a TRE, and have a high degree of confidence that their data (e.g. the information on how much electricity is being used right now) is not going to get in to the hands of someone who might use it against them (e.g. to work out when the home is unoccupied) - but the power company can also have from their side confidence that the data they receive is coming from one of their customers. If they need to reduce demand - in the extreme case by, say, remotely switching off somone's air conditioning unit fora time - they can send a signal back, confident that it will go to the right user, without knowing which customer that is. This approach can be generalised to many other situations: for example, the TRE could help to calculate a price for you to drive on a particular road at a particular time, without disclosing your movements to the transport authority. It could also pass back personalized (but anonymous) instructions on how to find a better route at the time.

ACORN-HAI is a large-scale multi-centre surveillance which focuses on the treatment and clinical outcomes of healthcare-associated bloodstream infection and ventilator-associated pneumonia. These severe infections are frequently caused by multidrug-resistant bacteria which have no effective treatment options. Prospectively collected case-based data of these infections are lacking and urgently needed to guide interventional trials. Our aims are firstly to establish a surveillance platform in hospitals with high burdens of drug resistance, in order to investigate target organisms and make up-to-date assessments on treatment options. Secondly through implementing the study across various regions and income settings, we aim to share expertise, optimise local engagement, and establish research teams and laboratory capacity. The enrollment criteria are based on the US Centers for Disease Control and Prevention criteria for healthcare-associated infection surveillance. Functional and mortality outcomes will be assessed on day 28. Bacterial isolates will be collected for genomic analysis to study geographical and temporal trends in resistance clones and genes. The target sample size is 500 participants per site over 30 study sites. ACORN-HAI study is a critical step towards assessing the burden of severe drug-resistant infections, and inform interventional trials to optimise treatment

Stochastic growth phenomena naturally emerge in a variety of physical and biological contexts, such as growth of combustion fronts or bacterial colonies, crystal growth on thin films, turbulent liquid crystals, etc. Even though all these phenomena might appear very diverse at a microscopic scale, they often have the same large-scale behaviour and are therefore said to belong to the same Universality Class. This in particular means that an in-depth analysis of those processes describing these large-scale behaviours is bound to give very accurate quantitative and qualitative predictions about the wide variety of extremely complicated real-world systems in the same class. Over the last 40 years, the Mathematics and Physics communities in a joint effort determined what were widely believed to be the only two universal processes presumed to capture the large-scale behaviour of random interfaces in one spatial-dimension, namely the Kardar-Parisi-Zhang and Edrwards-Wilkinson Fixed Points, and studied their Universality Classes. In a recent work, I established the existence of a third, new universality class, entirely missed by researchers, and rigorously constructed the universal process at its core, the Brownian Castle. The introduction of this novel class opens a number of new stimulating pathways and a host of exciting questions that this proposal aims at investigating and answering. The second pillar of this research programme focuses on two-dimensional random surfaces, which are particularly relevant from a physical viewpoint as they correspond to the growth of two-dimensional surfaces in a three-dimensional space. Despite their importance, two-dimensional growth phenomena are by far the most challenging and the least understood. Very little is known concerning their universal large-scale properties and the even harder quest for fluctuations has barely been explored. The present proposal's goal is to develop powerful and robust tools to rigorously address these questions and consequently lay the foundations for a systematic study of these systems and their features. The last theme of this research plan concerns the Anderson Hamiltonian, also known as random Schrödinger operator. The interest in such an operator is motivated by its ramified connections to a variety of different areas in Mathematics and Physics both from a theoretical and a more applied perspective. Indeed, the spectral properties of the Anderson Hamiltonian are related to the solution theory of (random) Schrödinger's equations or properties of the parabolic Anderson model, random motion in random media or branching processes in random environment. The Anderson Hamiltonian has attracted the attention of a wide number of researchers, driven by the ambition of fully understanding its universal features and the celebrated phenomenon Anderson localisation. This proposal will establish new breakthroughs and tackle long-standing conjectures in the field by complementing the existing literature with novel techniques.

The way in which bacteria divide in order to grow is a highly-coordinated process and requires a complex choreography of many proteins, working inside and outside the cell membrane. Many of these proteins have a functional relationship with the synthesis and coordination of the external cell shape determining polymer called peptidoglycan (PG). This polymer provides a structural scaffold for many cellular processes as well as mechanical strength and protection, which requires modification during the process of cell division. A critical point occurs during cell division when the "old" cell wall PG must be degraded to allow separation of newly synthesized cells and this function is provided by a variety of PG hydrolases associated with the cell division FtsE-FtsX protein complex. At Warwick we have recently contributed to a new understanding of how this process occurs in rod shaped, gram negative bacteria. However, the situation in respiratory infection associated, ovoid-shaped gram positive bacterial pathogens, including Streptococcus pneumoniae is unclear at present. Notably there is a direct interaction and functionally essential interaction between FtsEX and a single specific PG hydrolase called PcsB making it an attractive extracellular target to prevent pneumococcal disease. In this proposal we directly address questions concerning a particular essential enzyme and the complex it makes with cell division proteins in Streptococcus pneumoniae. The cell division proteins FtsE and FtsX form a complex together that spans the bacterial membrane and anchors an extracellular enzyme called PcsB that is required for cell division. The binding and hydrolysis of ATP inside the cell by FtsE is transmitted through its membrane anchor partner protein FtsX and results in a major conformational shape change in PcsB outside the cell which controls its ability to cut the peptidoglycan layer and allow cell division. Building on new structural data and models, genetic constructs, biochemical data, assays and international collaboration, the goal of this proposal is to understand the role of PcsB in complex with FtsEX and elucidate the molecular events linking cell division with PG degradative enzymes required for growth and division in S. pneumoniae. Drugs or vaccines that interfere with this process could prevent division and could provide routes to new treatments for pneumococcal and related infectious disease. The research proposed in this grant proposal forms part of an international effort with colleagues in the US and Singapore to combat this problem. The scientific principles that we will reveal may also have application in other, related bacterial species. Our work leading to this application, provides computer simulations, microbiological tools, techniques and biochemical approaches that can now be applied to the key biological questions of how are these proteins controlled, how do they function and how we might interfere with this this process to provide future antimicrobial strategies for human or animal health.