Anti-ENG Monoclonal antibody, clone NK8/29

In macroscopic dynamic models of fermentation processes, elementary modes (EM) derived from metabolic networks are often used to describe the reaction stoichiometry in a simplified manner and to build predictive models by parameterizing kinetic rate equations for the EM. In this procedure, the selection of a set of EM is a key step which is followed by an estimation of their reaction rates and of the associated confidence bounds. In this paper, we present a method for the computation of reaction rates of cellular reactions and EM as well as an algorithm for the selection of EM for process modeling. The method is based on the dynamic metabolic flux analysis (DMFA) proposed by Leighty and Antoniewicz (2011, Metab Eng, 13(6), 745-755) with additional constraints, regularization and analysis of uncertainty. Instead of using estimated uptake or secretion rates, concentration measurements are used directly to avoid an amplification of measurement errors by numerical differentiation. It is shown that the regularized DMFA for EM method is significantly more robust against measurement noise than methods using estimated rates. The confidence intervals for the estimated reaction rates are obtained by bootstrapping. For the selection of a set of EM for a given st oichiometric model, the DMFA for EM method is combined with a multiobjective genetic algorithm. The method is applied to real data from a CHO fed-batch process. From measurements of six fed-batch experiments, 10 EM were identified as the smallest subset of EM based upon which the data can be described sufficiently accurately by a dynamic model. The estimated EM reaction rates and their confidence intervals at different process conditions provide useful information for the kinetic modeling and subsequent process optimization.

Objective. While prosthetic hands with independently actuated digits have become commercially available, state-of-the-art human-machine interfaces (HMI) only permit control over a limited set of grasp patterns, which does not enable amputees to experience sufficient improvement in their daily activities to make an active prosthesis useful. Approach. Here we present a technology platform combining fully-integrated bioelectronics, implantable intrafascicular microelectrodes and deep learning-based artificial intelligence (AI) to facilitate this missing bridge by tapping into the intricate motor control signals of peripheral nerves. The bioelectric neural interface includes an ultra-low-noise neural recording system to sense electroneurography (ENG) signals from microelectrode arrays implanted in the residual nerves, and AI models employing the recurrent neural network (RNN) architecture to decode the subject's motor intention. Main results. A pilot human study has been carried out on a transradial amputee. We demonstrate that the information channel established by the proposed neural interface is sufficient to provide high accuracy control of a prosthetic hand up to 15 degrees of freedom (DOF). The interface is intuitive as it directly maps complex prosthesis movements to the patient's true intention. Significance. Our study layouts the foundation towards not only a robust and dexterous control strategy for modern neuroprostheses at a near-natural level approaching that of the able hand, but also an intuitive conduit for connecting human minds and machines through the peripheral neural pathways. Clinical trial: DExterous Hand Control Through Fascicular Targeting (DEFT). Identifier: NCT02994160.