At present, 40% of all leading compounds that emerge from drug discovery are not developed further due to their poor solubility. Currently, drug molecules are almost exclusively made into a medicine using a crystalline drug which has an inherent solubility disadvantage due to the lattice energy associated with its crystalline state that needs to be overcome before dissolution occurs. The amorphous state, where the molecules are completely disordered and hence the cohesive energy is smaller, is a potential alternative state for drug-molecule formulations. Given that the amorphous state is higher in energy, such drug formulations are currently perceived to be high risk, as it is not possible, using the existing technology and understanding, to predict their stability against recrystallisation reliably. In addition, there is still no comprehensive understanding of the physics of the amorphous state in general and the factors governing devitrification (the crystallisation process from the amorphous phase) even though this area of research has been the focus of very intense activities over the past decades. Unforeseen stability issues due to recrystallisation could lead to enormous costs for pharmaceutical companies if such formulations fail during the later stage clinical trials or, even more catastrophically, once the product is on the market. However, the improvement of solubility in the amorphous state would be sufficient to permit greater than 50% of poorly soluble leading compounds to be selected as candidates for the drug-development pipeline. This would permit an extensive range of hitherto untested chemistries to move through to the clinic to address unmet therapeutic needs for patient benefit. Here, we aim to develop a better understanding of structural changes occurring in organic amorphous formulations of drugs, with the ultimate goal of improving their efficacy and stability. This proposal is developed around the ability to quantify directly terahertz and/or picosecond-nanosecond inter-molecular dynamics that govern the crystallisation in organic amorphous systems. The majority of experimental evidence will be gathered by means of terahertz time-domain spectroscopy (THz-TDS) and low-frequency Raman spectroscopy but will be complemented by theoretical and simulational studies, and other experimental techniques as necessary. There are two ultimate goals of the proposed work: 1) To develop an analytical method that can be used to quantify the likelihood of structural changes, ultimately culminating in crystallisation, occurring in amorphous materials over extended periods. Furthermore, to allow a systematic optimisation of amorphous drug formulations and their storage conditions with respect to their stability against structural changes. 2) To provide high-quality experimental data to stimulate and support the development of theory aimed at better understanding the fundamental physics of non-equilibrium organic solids. If successful, the terahertz or Raman methods could be implemented for drug-development activities almost immediately, as such turn-key equipment is now commercially available and, once we are able to develop the detailed understanding as outlined in this proposal, they can be operated and the data interpreted by technicians, much like any other analytical technique today. The lab-based measurements proposed here could further remove the requirement for costly and time-consuming measurements at central facilities, such as neutron sources, for similar analysis, and thus free up this critical resource for other research activities.

s-NEBULA explores and develops a revolutionary approach to TeraHertz (THz) technology, both for generation and detection of THz radiation, initiating the new field of spin-based TeraHertz (s-THz) technology, a game changer for the future of THz field. The ambition of s-NEBULA is to provide a platform of room-temperature innovative spin-based THz building blocks, arising from novel combinations of magnetism and optics. s-NEBULA will provide cutting-edge solutions to solve bottleneck scientific issues in the THz field motivated by clear needs in judiciously chosen target applications. These include variable-baseline broadband pulsed emitters and voltage-controlled compact detectors for non-destructive testing (NDT), intrinsically-modulated CW emitters for THz communication and polarization-programmable emitters for ellipsometry. We will demonstrate innovative schemes for THz emission using spin-orbit interfaces targeting optically driven s-THz pulsed emitters with bandwidth > 20 THz, with enormous potential for NDT applications. For THz communication, data traffic densities of several Tbps/km2 are predicted for 5G networks, but not a single THz data link beyond2 THz s-NEBULA will develop high-power tunable CW emitters working beyond 5 THz. Besides, we will investigate a disruptive approach combining antiferromagnetic materials with direct voltage rectification effects, targeting a tunable & compact detector, key element for on-chip THz systems of tomorrow. Furthermore, combining THz radiation with magnetism enables an extra lever to control the emitted wave; intrinsic modulation/demodulation becomes possible, as well as polarization control for innovative schemes in ellipsometry. All these approaches are not possible with existing THz technologies. The consortium gathers leading European expertise in significantly diverse areas (optics, magnetism, materials preparation, advanced theory, industrial integration, THz metrology) that will enable multi-disciplinary work.

SELECTIVELI represents a strong BBI consortium, including full members Sappi (SAPPI), Idener (IDENER), associated members Vito (VITO), Leitat (LEITAT) and Sintef (SINTEF) in addition to industrial partners Chimar (CHIMAR) and LCEngineering (LCE) and leading experts in the field of preparative electrochemistry, University of Mainz (JGU). SELECTIVELI will provide proof of concept on the laboratory scale (at least TR3) to demonstrate the potential for converting low cost lignosulfonate feedstocks (by-product from paper and pulp industry) into high value bio-sustainable chemicals through the following: (I) Development and optimisation of the electrochemical process to convert bio-based feedstock (lignosulfonates) into target monomers, some of which can be converted into polymers for study in further downstream processes. (II) Development and optimisation of downstream separation and purification processes to extract the target products and conversion of intermediate building block monomers (mixed phenolic derivatives) into higher value polymers (III) Modelling the process to (a) prepare process designs and scale up strategies for future industrial scale production and ensuring commercial viability (b) assessing energy requirements and proving the process is capable of benefitting from surplus energy and accommodating energy fluctuations. (IV) Conducting a full life-cycle analysis to establish that a future biorefinery process can reduce environmental footprint of a value chain.

The EUPEX consortium aims to design, build, and validate the first EU platform for HPC, covering end-to-end the spectrum of required technologies with European assets: from the architecture, processor, system software, development tools to the applications. The EUPEX prototype will be designed to be open, scalable and flexible, including the modular OpenSequana-compliant platform and the corresponding HPC software ecosystem for the Modular Supercomputing Architecture. Scientifically, EUPEX is a vehicle to prepare HPC, AI, and Big Data processing communities for upcoming European Exascale systems and technologies. The hardware platform is sized to be large enough for relevant application preparation and scalability forecast, and a proof of concept for a modular architecture relying on European technologies in general and on European Processor Technology (EPI) in particular. In this context, a strong emphasis is put on the system software stack and the applications. Being the first of its kind, EUPEX sets the ambitious challenge of gathering, distilling and integrating European technologies that the scientific and industrial partners use to build a production-grade prototype. EUPEX will lay the foundations for Europe's future digital sovereignty. It has the potential for the creation of a sustainable European scientific and industrial HPC ecosystem and should stimulate science and technology more than any national strategy (for numerical simulation, machine learning and AI, Big Data processing). The EUPEX consortium – constituted of key actors on the European HPC scene – has the capacity and the will to provide a fundamental contribution to the consolidation of European supercomputing ecosystem. EUPEX aims to directly support an emerging and vibrant European entrepreneurial ecosystem in AI and Big Data processing that will leverage HPC as a main enabling technology.