Alternatives to animal models and their application in the discovery of species susceptibility to SARS-CoV-2 and other respiratory infectious pathogens: A review.

The emergence of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inspired rapid research efforts targeting the host range, pathogenesis and transmission mechanisms, and the development of antiviral strategies. Genetically modified mice, rhesus macaques, ferrets, and Syrian golden hamsters have been frequently used in studies of pathogenesis and efficacy of antiviral compounds and vaccines. However, alternatives to in vivo experiments, such as immortalized cell lines, primary respiratory epithelial cells cultured at an air-liquid interface, stem/progenitor cell-derived organoids, or tissue explants, have also been used for isolation of SARS-CoV-2, investigation of cytopathic effects, and pathogen-host interactions. Moreover, initial proof-of-concept studies for testing therapeutic agents can be performed with these tools, showing that animal-sparing cell culture methods could significantly reduce the need for animal models in the future, following the 3R principles of replace, reduce, and refine. So far, only few studies using animal-derived primary cells or tissues have been conducted in SARS-CoV-2 research, although natural infection has been shown to occur in several animal species. Therefore, the need for in-depth investigations on possible interspecies transmission routes and differences in susceptibility to SARS-CoV-2 is urgent. This review gives an overview of studies employing alternative culture systems like primary cell cultures, tissue explants, or organoids for investigations of the pathophysiology and reverse zoonotic potential of SARS-CoV-2 in animals. In addition, future possibilities of SARS-CoV-2 research in animals, including previously neglected methods like the use of precision-cut lung slices, will be outlined.

NMR magnets for portable applications using 3D printed materials.

In this paper, we introduce 3D printing as a possibility for realizing lightweight, yet high-precision NMR magnets. Using a commercially available filament containing steel particles allows for the realization of critical components of NMR magnets such as pole pieces and even the flux-conducting yoke. In contrast to shimming structures made of iron, 3D printed structures made of the lightweight filament allow for a robust and inexpensive way of realizing high-performance NMR magnets for future portable NMR applications. We demonstrate the versatility and achievable high performance of the proposed solution with two different H-shaped NMR magnets. In the first magnet, the 3D-printed filament is used to realize the yoke that guides the magnetic flux inside the magnet, providing the potential for a substantial weight reduction compared to a conventional iron yoke. In the second magnet, we use the 3D-printed material to realize arbitrarily shaped passive shim structures. Numerical size and shape optimizations using non-uniform rational basis splines (NURBS) have been applied to obtain the optimal geometry. The two manufactured magnets achieve measured NMR spectral line widths of 54 ppm and 250 ppm, respectively. Our results clearly demonstrate the efficiency and versatility of the proposed design and optimization approach.