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The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.

β-Thalassemia is a genetic anemia caused by partial or complete loss of β-globin synthesis, leading to ineffective erythropoiesis and RBCs with a short life span. Currently, there is no efficacious oral medication modifying anemia for patients with β-thalassemia. The inappropriately low levels of the iron regulatory hormone hepcidin enable excessive iron absorption by ferroportin, the unique cellular iron exporter in mammals, leading to organ iron overload and associated morbidities. Correction of unbalanced iron absorption and recycling by induction of hepcidin synthesis or treatment with hepcidin mimetics ameliorates β-thalassemia. However, hepcidin modulation or replacement strategies currently in clinical development all require parenteral drug administration. We identified oral ferroportin inhibitors by screening a library of small molecular weight compounds for modulators of ferroportin internalization. Restricting iron availability by VIT-2763, the first clinical stage oral ferroportin inhibitor, ameliorated anemia and the dysregulated iron homeostasis in the Hbb(th3/+) mouse model of β-thalassemia intermedia. VIT-2763 not only improved erythropoiesis but also corrected the proportions of myeloid precursors in spleens of Hbb(th3/+) mice. VIT-2763 is currently being developed as an oral drug targeting ferroportin for the treatment of β-thalassemia.

Automotive manufacturing systems are high investment assets in need of continuous upgrades and changes to remain relevant and effective. The complexity of such a system is reflected in the difficulty of making holistically informed decisions regarding the upgrades and changes. To reach holistic and sound decisions it is important to collaborate between departments, experts, and operational actors during the planning and development of upgrades and changes. Such collaboration should be supported by tools, models, and methods that facilitate understanding and enable the users to express their input and feedback in a clear and understandable manner. This chapter describes the development and evaluation of one set of tools. The developed tools combine 3D imaging and virtual reality technologies to facilitate the creation of decision support models that are accurate, realistic, and intuitive to understand. The developed tools are evaluated by industrial engineers in the area of manufacturing R&D.

European companies of today are involved in many stages of the product life cycle. There is a trend towards the view of their business as a complex industrial product-service system (IPSS). This trend shifts the business focus from a traditional product oriented one to a function oriented one. With the function in focus, the seller shares the responsibility of for example maintenance of the product with the buyer. As such IPSS has been praised for supporting sustainable practices. This shift in focus also promotes longevity of products and promotes life extending work on the products such as adaptation and upgrades. Staying competitive requires continuous improvement of manufacturing and services to make them more flexible and adaptive to external changes. The adaptation itself needs to be performed efficiently without disrupting ongoing operations and needs to result in an acceptable after state. Virtual planning models are a key technology to enable planning and design of the future operations in parallel with ongoing operations. This chapter presents an approach to combine digitalization and virtual reality (VR) technologies to create the next generation of virtual planning environments. Through incorporating digitalization techniques such as 3D imaging, the models will reach a new level of fidelity and realism which in turn makes them accessible to a broader group of users and stakeholders. Increased accessibility facilitates a collaborative decision making process that invites and includes cross functional teams. Through such involvement, a broader range of experts, their skills, operational and tacit knowledge can be leveraged towards better planning of the upgrade process. This promises to shorten lead times and reduce risk in upgrade projects through better expert involvements and shorter iterations in the upgrade planning cycle.