NIHRDataInsights/HRCSData huggingface dataset:
Title: Convergent Acyliminium Methodology: Diversity in Heterocyclic Scaffolds
Funder: Engineering and Physical Sciences Research Council

Abstract: Heterocyclic compounds are the cornerstone of the pharmaceutical and agrochemical industries. As part of our on-going research programme geared towards the synthesis of heterocyclic systems of biological interest, we have placed a great deal of emphasis on designing streamlined and environmentally friendly cascade and telescoped processes leading to valuable heterocycles. We now propose to develop Convergent Acyliminium Methodology (CAM) to establish an efficient "one-pot" route to convert readily available imines and carboxylic acids into a diverse range of highly functionalised heterocyclic systems We believe that such a simple and reliable procedure leading to novel heterocyclic scaffolds will be a valuable addition to existing "diversity-oriented" synthetic protocols and will be of great utility to synthetic chemists in both academia and industry. Preliminary studies have been carried out which establish the viability of this novel approach; the main aims of the proposal are therefore: (i) to optimise the novel Convergent Acyliminium Methodology (CAM) to develop an efficient "one-pot" route to convert readily available imines and carboxylic acids into a diverse range of heterocyclic systems, (ii) to expand the range of acylating agents to include benzannelated examples and functionalized sulfonic acids, phosphonic acids, chloroformates and isocyanates, (iii) to explore asymmetric catalysis to prepare heterocycles in enantio-enriched forms, (iv) to extend the range of imine substrates to encompass acyclic imines, imidates, oxazolines, imidazolines and thiazolines, (v) to exploit the CAM sequence in an iterative sense utilising repeated ring-expansions to produce medium-sized and macrocyclic lactams and cyclic peptides, (vi) to extend the methodology to prepare the complex natural product, 'upenamide, in order to showcase this new synthetic approach, (vii) to apply, and therefore validate, the new CAM sequence in simple target synthesis with jamtinine and loracarbef as possible targets (although targets from collaborators will also be considered). It is our aim to develop this new procedure into a powerful synthetic procedure with far-reaching applications in academic research, industrial medicinal chemistry and scale-up processes (letters of support from AstraZeneca and Novartis (pharma) and Bayer (Agro) are attached and plans for collaborations with these companies are well advanced). This ambitious programme will be carried out by a PDRA over a 3 year period.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Advancing the Geometric Framework for Computational Statistics: Theory, Methodology and Modern Day Applications
Funder: Engineering and Physical Sciences Research Council

Abstract: The vision of this research is to formalise the geometric foundations of computational statistics and provide the tools and analytic results required to realise the ambition of developing the advanced statistical methodology that is essential to address emerging inference problems of major importance across the sciences and industry. As ever more demanding and ambitious applications of existing statistical inference methods are being considered, the capabilities of computational statistics tools are constantly being stretched, often beyond what is practically feasible. For example the potential to gain insights into the mechanisms of cellular function, elucidating ecological dynamics; improving neurological diagnostics, and uncovering the deep mysteries of the cosmos are only some of the ongoing scientific studies that are heavily reliant on statistical inference methods and are placing unparalleled demand on the current capabilities of available statistical methodology. This situation motivates continual innovation in the development of statistical methods for the quantification of uncertainty. The aim of this proposed research is to be more ambitious and go much further in establishing a novel paradigm that underpins the advancement of next generation computational statistical methods by formalising and developing advanced Monte Carlo methods. The geometric foundations of computational statistics will be formalised within this proposed research in a way that reaches beyond traditional interfaces between statistical and mathematical sciences.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS
Health categories: GENERIC HEALTH RELEVANCE
Title: Integrated Molecular Design of Melt-processable Bioresorbable Engineering Nanocomposites for Healthcare (BENcH)
Funder: Engineering and Physical Sciences Research Council

Abstract: This proposal will deliver novel, integrated methodologies for the design and scalable manufacture of next generation resorbable polymer nanocomposites, linking the science and engineering principles which underpin successful processing of such materials. This will enable new smart health-care materials in applications from bone fracture fixation to drug delivery. The methodologies will be optimised on a system comprising novel nanoparticles, selected blends of medical-grade degradable polymer and specifically designed molecular dispersants. Optimised methodologies will be applied at scale on industrial equipment to produce demonstrator resorbable implants with specific structural attributes and degradation timescales. Wider applications include degradable food packaging and products requiring end-of-life disposal.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: A rigorous statistical framework for estimating the long-term health effects of air pollution
Funder: Engineering and Physical Sciences Research Council

Abstract: The adverse health effects resulting from exposure to air pollution are well known across the world, and have a substantial financial and public health impact. For example, in the UK air pollution is estimated to reduce life expectancy by 6 months, with


Research activity codes: 2.5 RESEARCH DESIGN AND METHODOLOGIES (AETIOLOGY)
Health categories: GENERIC HEALTH RELEVANCE
Title: International Centre for Mathematical Sciences Programme 2012-2016
Funder: Engineering and Physical Sciences Research Council

Abstract: The International Centre for Mathematical Sciences in Edinburgh is one of the UK's most important resources in the mathematical sciences. The centre's primary role is to organise research workshops in mathematics and related areas of science and to involve users from other sciences and industry in these activities. In the 20 years since it was founded the centre has established a superb reputation for hosting well-organised meetings at the highest scientific level on the most important and innovative topics in the mathematical sciences. Proposed meetings are subjected to a rigorous reviewing process by referees of international standing and selected only if they are of very high quality. In any 2 or 3 year period, ICMS workshops cover an unusually broad and exciting range of topics. The centre monitors quality through participant questionnaires, workshop reports that are assessed by the programme committee and is introducing follow up questionnaires asking participants to list collaborations and other research outcomes generated by meetings. The centre has a dedicated knowledge transfer officer whose job is to identify potential users of new mathematical ideas from outside the academic community and to stage events (either in connection with research workshops or independently) to involve those users. Some 50 of the world's largest companies have sent representatives to ICMS meetings in the last 3 years, covering healthcare, the oil industry, the financial industry, defence, engine manufacture and computing. ICMS also runs a research-in-groups programme to enable small groups of researchers to work together for a short period of intensive collaboration. It provides a particularly cost effective way of promoting international collaborations by UK scientists. Research workshops play a particularly crucial role in the development of mathematics. Important research collaborations often begin at such meetings and early career researchers gain a significant part of their training at workshops and conferences. ICMS events have attracted many of the world's leading mathematicians to Britain and have involved many of the world leaders who work here. Younger prticipants, many of whom will later move into industry, also have a chance to make industrial contacts at these meetings.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;1.5 RESOURCES AND INFRASTRUCTURE (UNDERPINNING)
Health categories: GENERIC HEALTH RELEVANCE
Title: CRITICAL MASS: Collective radiation-beam-plasma interactions at high intensities
Funder: Engineering and Physical Sciences Research Council

Abstract: This proposal describes a programme of research on single-particle and collective radiation-beam-plasma interactions at high field intensities, production of high-brightness particle beams with femtosecond to attosecond duration, new sources of coherent and incoherent radiation that are both compact and inexpensive, new methods of accelerating particles which could make them widely available and, by extending their parameter range, stimulate new application areas. An important adjunct to the proposal will be a programme to apply the sources to demonstrate their usefulness and also provide a way to involve industry and other end-users. The project builds on previous experiments and theoretical investigations of the Advanced Laser Plasma High-energy Accelerators towards X-rays (ALPHA-X) project, which has demonstrated controlled acceleration in a laser-plasma wakefield accelerator (LWFA), initial applications of beams from the LWFA and demonstrations of gamma ray production due to resonant betatron motion in the LWFA. The programme will have broad relevance, through developing an understanding of the highly nonlinear and collective physics of radiation-matter interactions, to fields ranging from astrophysics, fusion and nuclear physics, to the interaction of radiation with biological matter. It will also touch on several basic problems in physics, such as radiation reaction in plasma media and the development of coherence in nonlinear coupled systems


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE
Title: Modelling the self-assembly of DNA multi-arm motifs
Funder: Engineering and Physical Sciences Research Council

Abstract: DNA is famous for its double helical structure, in which two strands wide around each other held together by the very specific interactions between the DNA bases that was first discovered by Watson and Crick, namely that adenine (A) bonds with thymine (T) and cytosine (C) bonds with guanine (G). The two strands are said to be complementary, because at each nucleotide the bases pair in the Watson-Crick fashion (A-T, and C-G). However, the specificity of the base pairing allows other structures other than one single double helix to be programmed into a set of DNA strands. For example, if you have 3 types of strands, say P, Q and R, where the first half of P is complement to half of Q, and the second half is complementary to half of R, and the remaining halves of Q and R are complementary, the system will want to form a structure with three double helical sections meeting at a junction. This basic approach can be scaled up to make a whole array of precisely-ordered structures on the nanometer length scale that assemble themselves driven by the desire of complementary stretches of DNA molecules to pair up. This field is called DNA nanotechnology, and in this proposal we wish to study nanostructures called DNA multi-arm motifs. The 3-arm example of this class of structures is somewhat similar to the junction mentioned above, except that each arm is made up of two parallel double helices. By designing these motifs so that there are short single-stranded overhangs at the each of arm that are complementary to the overhangs at the ends of other arms, these motifs can be made to form a whole variety of larger structures. For example, the 3-arm motifs can form tetrahedra, dodecahedra and buckyballs (all polyhedra where 3 edges meet at a vertex) depending on the precise design and the conditions under which they assemble, In experiments, the researchers are able to see if their designed sequences successfully assemble into the target structure, but cannot see how they manage to achieve this. This is where computer modelling and this proposal fits in. We want to use techniques that we recently developed to model DNA to visualize the mechanisms by which these remarkable molecules are able to so reliably self-assemble. The insights that we hope to obtain will be of great help to experimentalists, as it will give them a better idea of why some of their designs are successful whereas others fail to do what is expected. This in turn will help them to make the design procedure more rational and hence more likely to succeed. Hopefully, this will enable the experimentalists to significantly increase the types of structures they can produce.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE
Title: Laser-Guided nanoparticles and Cell Scalextrics
Funder: Engineering and Physical Sciences Research Council

Abstract: Steering nanoparticle transport in human cells - why is this important? Viruses seem to travel effortlessly into tissues and cells, being transported selectively in the body to reach the sites where they can cause most harm. They do this by breaching cell


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;5.2 CELLULAR AND GENE THERAPIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Development And Application Of Fibre-Laser Based Excitation Sources For Biomedical Photoacoustic Imaging
Funder: Engineering and Physical Sciences Research Council

Abstract: The aim of this research is to develop a range of novel fibre based laser systems for use in a promising new medical and biological imaging technique. The technique, called photoacoustic imaging, works by forming an image from acoustic waves generated by


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: High Frequency Degenerate Mode Acoustic Sensors
Funder: Engineering and Physical Sciences Research Council

Abstract: The purpose of this research bid is to investigate and characterise a completely new form of acoustic surface wave resonator and to apply the concept to the design and fabrication of ultra-robust inertial rate and ultra-sensitive mass sensors. The form greatly simplifies manufacture and packaging, uses a cheap substrate material, and, depending on the application, is robust to the influences of temperature, load and surrounding fluid. The applications are targeted at the defence and healthcare industries, both of which have recognised opportunities for creating a knowledge economy, influencing security, and promoting health and well-being. In defence there is a well established market for low performance rate gyros and the basic driver is cost. However there is an important gyroscopic application in guided munitions/shells which still seeks a satisfactory solution. Here the gyro (currently a fragile piece) has to be very low cost and structurally robust enough not to be influenced by the extreme inertia loads and vibration experienced during launch and in flight. Also, to be able to operate without the requirement of an evacuated case-all MEMS gyros operate under vacuum- would be a major packaging advantage. The proposed design offers a way forward for this application and will challenge low cost gyro applications in automotive and consumer markets. The application as a mass sensor is for the detection and monitoring of disease in healthcare and bio-detection in defence. The potential for the sensor to be miniaturizable, portable, cheap to mass produce, simple readout electronics, temperature/environment compensated with high sensitivity and multiplex possibilities make it an attractive platform. Success in this area would have a positive impact on the effectiveness of public health care and security, particularly if the sensor and its supporting system could be made at a low enough cost to be become attractive system for use at the first point of need. A major advantage of using a degenerate mode resonator as the mass sensor is that the recording system is much simplified as it does not require the sensor to be housed in a temperature controlled environment. Owing to their improved performance/robustness and low manufacturing costs, the proposed sensors have the potential to replace existing SAW as well as MEMS sensors. Moreover, as a result of their wide-ranging applications, successful development would stimulate the manufacturing industry in the UK.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: GENERIC HEALTH RELEVANCE
Title: Predicting the Volume of Distribution of Drugs and Toxicants with Data Mining Methods
Funder: Engineering and Physical Sciences Research Council

Abstract: Paracelsus, a physician in the early 16th century, is credited with the phrase: "All things are poison, and nothing is without poison; only the dose permits something not to be poisonous" (http://en.wikipedia.org/wiki/Paracelsus). Despite significant advances in pharmacology in the last decades, at present it is still very difficult to find good answers to the questions of how much, how often and for how long a drug should be given to a patient, in order to maximize its therapeutic effect and minimize its adverse effects. These problems are the central concern of the related areas of pharmacokinetics and pharmacodynamics. Pharmacokinetics is concerned with how a drug is processed by the body, i.e., the relationship between drug input parameters (e.g. amount of drug in a dose and dose frequency) and the concentration of the drug in the body with time. In contrast, pharmacodynamics is concerned with how a drug affects the body, i.e., the relationship between drug concentration and the therapeutic and adverse effects of the drug with time. This project focuses on an important pharmacokinetics problem: how to estimate the volume of distribution of a drug, which represents the volume into which a drug is distributed once it has entered systemically into the body. Estimating a drug's volume of distribution is important because it predicts the drug's plasma concentration for a given amount of drug in the body and it influences the drug's half-life, which in turn is very important to determine the correct dosage regimen that clinicians should prescribe to patients. This project aims at developing new computational data mining methods to predict the volume of distribution of drugs. The data mining context for this project is the regression task, where the system is given a set of instances representing a set of objects, where each instance consists of a target (response) attribute (or dependent variable) and a set of predictor attributes (features or independent variables) describing an object. Then the system discovers a regression model that predicts the value of the target attribute for an instance based on the values of its predictor attributes. In this project, the objects to be classified will be chemical compounds or medical drugs, the target attribute to be predicted will be a drug's volume of distribution and the predictor attributes will refer to several types of molecular and physicochemical properties of drugs. The data mining methods to be developed in the project will be compared against traditional data analysis methods used for predicting a drug's volume of distribution.


Research activity codes: 5.1 PHARMACEUTICALS;8.4 RESEARCH DESIGN AND METHODOLOGIES (HEALTH SERVICES)
Health categories: GENERIC HEALTH RELEVANCE
Title: Micro Materials NanoTest Vantage Testing Suite with NTX4Controller
Funder: Engineering and Physical Sciences Research Council

Abstract: The proposed bid will provide the UK with a world leading nanomechanical and nanotribological testing facility, with access available to all UK academic institutions and UK industry. The Micro Materials Vantage System represents a step-change in repositioning accuracy and testing speed than previous systems It provides the ability to undertake 6 fundamentally different mechanical or tribological tests (Indentation, Scratch, Impact, Fatigue, Wear, Fretting), in a range of different environments, offering the ability to tailor tests to simulate service environments. The ability to mechanically and tribologically test at the nano-scale is vitally important for a number of different scientific disciplines. In Tribology, the behaviour of macro-scale contacts such as the bearing surface contact of a hip joint, is governed by the interfacial interactions at the nano-scale. Assessment of the nanomechanical and nanotribological behaviour of the surfaces, and the investigation of the surface layers or tribofilms formed during contact motion, is vital to the fundamental understanding of the contacts behaviour, and it provides crucial information for predictive modelling. In manufacturing and materials science, new manufacturing and processing techniques such as laser processing and electrical discharge machining, produce microstructures, thin surface layers and textures on material surfaces which are of the order of microns in size. This means conventional hardness, wear and impact testing methods are simply not sufficient to assess them. This microstructure and texture formation can enhance and detract from the performance of the component in service; therefore the ability to test relevant properties at the appropriate scale is vital. Coatings science is a field which spans a multitude of disciplines ranging from ship antifouling paint films through to hard coatings for the turbine blades of jet engines. While these coatings can vary in thickness, hard coatings for wear, impact and erosion resistance can be typically 1-50 microns thick with properties tailored to fit their purpose. The low thicknesses of the coatings mean their adhesion to the substrate and mechanical properties which are vital to the prediction of their performance can only be accessed through nano-scale testing. Many natural materials such as bone and cartilage have complex hierarchical structures which extending down to the nano-scale. Changes occurring at the nano and micro-scale govern the macro-scale properties and performance and the ability to assess these levels provides valuable insights into the origins of conditions such as Osteoarthritis and Osteoporosis.


Research activity codes: 1.3 CHEMICAL AND PHYSICAL SCIENCES
Health categories: GENERIC HEALTH RELEVANCE