Epidural electrical stimulation (EES) targeting the dorsal roots of lumbosacral segments restored walking in people with spinal cord injury (SCI). However, EES was delivered with multielectrode paddle leads that were originally designed to target the dorsal column of the spinal cord. Here, we hypothesized that an arrangement of electrodes targeting the ensemble of dorsal roots involved in leg and trunk movements would result in superior efficacy, restoring more diverse motor activities after the most severe SCI. To test this hypothesis, we established a computational framework that informed the optimal arrangement of electrodes on a new paddle lead and guided its neurosurgical positioning. We also developed a software supporting the rapid configuration of activity-specific stimulation programs that reproduced the natural activation of motor neurons underlying each activity. We tested these neurotechnologies in three individuals with complete sensorimotor paralysis, as part of an ongoing clinical trial (clinicaltrials.gov, NCT02936453). Within a single day, activity-specific stimulation programs enabled the three individuals to stand, walk, cycle, swim, and control trunk movements. Neurorehabilitation mediated sufficient improvement to restore these activities in community settings, opening a realistic path to support everyday mobility with EES in people with SCI.

No abstract

This microreview summarizes recent research in the field of artificial nucleases, in particular those based on copper(II) in an N‐donating ligand environment. This review is divided into three parts describing different ligand classes that have shown promising results in DNA cleavage chemistry: aromatic N‐donors, aliphatic N‐donors, and peptide ligands. Whereas nature has created very efficient nucleases, artificial nucleases aim at different selectivities and higher stability under various conditions. Artificial nucleases based on metal complexes comprise Lewis acidic or redox‐active metal centers allowing for either hydrolytic or oxidative DNA cleavage. The focus of our research and thus also of this microreview is copper, whose CuII ion combines both properties. Depending on the ligand scaffold and reaction conditions, either pathway or even both are thus conceivable. Those different pathways lead to molecular biological and medicinal applications.

No abstract

Y-Ba-Cu-O melt processed samples were prepared from mixtures of powders (starting average particle size ranging from to ) with and 1 wt% or 1 wt% . The resulting microstructure of the samples was composed of network and low concentration regions with size and morphology correlating with the starting powder size independently of the holding time in the melted state. The 211 particle size was smaller for Ce doped samples than for Pt doped samples. The differences in porosity of Pt and Ce doped samples were related to the changes in the interfacial energy of the constituent phases.

Data-driven models are becoming increasingly popular in engineering, on their own or in combination with mechanistic models. Commonly, the trained models are subsequently used in model-based optimization of design and/or operation of processes. Thus, it is critical to ensure that data-driven models are not evaluated outside their validity domain during process optimization. We propose a method to learn this validity domain and encode it as constraints in process optimization. We first perform a topological data analysis using persistent homology identifying potential holes or separated clusters in the training data. In case clusters or holes are identified, we train a one-class classifier, i.e., a one-class support vector machine, on the training data domain and encode it as constraints in the subsequent process optimization. Otherwise, we construct the convex hull of the data and encode it as constraints. We finally perform deterministic global process optimization with the data-driven models subject to their respective validity constraints. To ensure computational tractability, we develop a reduced-space formulation for trained one-class support vector machines and show that our formulation outperforms common full-space formulations by a factor of over 3000, making it a viable tool for engineering applications. The method is ready-to-use and available open-source as part of our MeLOn toolbox (https://git.rwth-aachen.de/avt.svt/public/MeLOn).

The microstructure of YBaCuO/Ag composite materials prepared from precursors YBa2Cu3O7(Y123) + 0.24Y2O3 + Ag2O with different amounts of Ag2O addition, grown at different furnace cooling rates, was analysed quantitatively by image processing of optical microscopy images. The critical average Ag concentration in the melt for the start and the steady state of Ag particle formation was estimated. A higher growth rate causes elongation and alignment of Ag particles in the growth direction. Type B monotectic crystallization was identified to take place in the hypermonotectic compositions. Monotectic and hypermonotectic types of Ag particles, which differ in size and morphology, were distinguished and the mechanisms of their formation proposed, taking into account the influence of both Ag and Y2O3 additions on the phase equilibria and considering a certain solubility of Ag in Y123.

DNA can be oxidatively cleaved by copper complexes of the ATCUN peptide (amino terminal Cu(II)- and Ni(II)-binding motif). In order to investigate the fate of the metal ion throughout this process, we have exploited quenching/dequenching effects of conjugated fluorophores.