Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile

In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also

Infektionsmedizinische und chirurgische Herausforderungen durch Carbapenem-resistente bakterielle Erreger bei der Versorgung Kriegsverletzter aus der Ukraine

Aufgrund von Hygienedefiziten und dem sehr breiten, kalkulierten Antibiotikaeinsatz bei zeit¬gleich offener Wundbehandlung in ukrainischen Militärkrankenhäusern ist das Risiko für schwerwiegende Wundinfektionen mit multiresis¬tenten Erregern (MRE) bei Übernahme ziviler Kriegsopfer hoch. Insofern kommt der Surveillance mit risikoadaptiertem Screening auf MRE, welches am Universitätsklinikum Leipzig seit 2012 durchgeführt wird, eine große Bedeutung zu. Es werden die Komplexität der Versorgung Kriegsverletzter aus der Ukraine sowie die damit einhergehenden Infektions- und Resistenzprobleme dargestellt und auf die Notwendigkeit eines interdisziplinären und -professionellen Managements hingewiesen.Peer Reviewe

Hybrid Approach to State Estimation for Bioprocess Control

An improved state estimation technique for bioprocess control applications is proposed where a hybrid version of the Unscented Kalman Filter (UKF) is employed. The underlying dynamic system model is formulated as a conventional system of ordinary differential equations based on the mass balances of the state variables biomass, substrate, and product, while the observation model, describing the less established relationship between the state variables and the measurement quantities, is formulated in a data driven way. The latter is formulated by means of a support vector regression (SVR) model. The UKF is applied to a recombinant therapeutic protein production process using Escherichia coli bacteria. Additionally, the state vector was extended by the specific biomass growth rate µ in order to allow for the estimation of this key variable which is crucial for the implementation of innovative control algorithms in recombinant therapeutic protein production processes. The state estimates depict a sufficiently low noise level which goes perfectly with different advanced bioprocess control applications

Correction: Risk Factors for Multi-Drug Resistant Pathogens and Failure of Empiric First-Line Therapy in Acute Cholangitis.

[This corrects the article DOI: 10.1371/journal.pone.0169900.]