Modeling the effect of gradients on cell culture performance in various large scale bioreactors

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Modeling the effect of bioreactor pH on Chinese Hamster Ovary (CHO) cell metabolism and site-specific N-linked glycosylation of VRC01

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Process design of a fully integrated continuous biopharmaceutical process using economic and ecological impact assessment

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A Discrete-time Scheduling Model for Continuous Power-intensive Processes Considering Fatigue of Equipment

In the light of the growing renewable energy generation, matching of electricity supply and demand has become increasingly challenging. By participating in demand side management programs, industry can contribute to counter this challenge. However, the frequent adjustment of operation conditions according to volatile electricity prices leads to additional dynamic loads for the equipment. In this work, a mixed-integer linear programming based discrete-time model is proposed for scheduling of a single air separation unit, explicitly considering fatigue of equipment occurring during transient operation. Besides constraints for describing the feasible region and the process dynamics, this model includes constraints for considering mechanical fatigue of some key equipment. The resulting model is applied to investigate the impact of mechanical constraints on the potentials of demand side management.BMBF, 03SFK3X1, Verbundvorhaben SynErgie: Synchronisierte und energieadaptive Produktionstechnik zur flexiblen Ausrichtung von Industrieprozessen auf eine fluktuierende Energieversorgung. X1_Linde: Erforschung und Demonstration von Industrieprozessen und Produktionssystemen im Hinblick auf energetische Nachfrageflexibilitä

Hybridizing Discrete- and Continuous-Time Models for Batch Sizing and Scheduling Problems

This paper proposes a new hybrid technique called “partial parameter uniformization” (hereafter PPU). The technique simplifies problems by ignoring the different values that certain problem parameters can take, which may facilitate the solution of some hard combinatorial optimization problems. PPU is applied to complex batch sizing and scheduling problems. Some information can be obtained from a discrete-time model in which job durations have been made uniform. This information is then exploited by a more detailed continuous-time model to generate feasible solutions and further improve these solutions. Good, or optimal solutions to the Westenberger and Kallrath Benchmark problems have been obtained in this way, at relatively low computational cost, as have solutions to the newer problems of Blömer and Günther

Simulating Microdosimetry in a Virtual Hepatic Lobule

The liver plays a key role in removing harmful chemicals from the body and is therefore often the first tissue to suffer potentially adverse consequences. To protect public health it is necessary to quantitatively estimate the risk of long-term low dose exposure to environmental pollutants. Animal testing is the primary tool for extrapolating human risk but it is fraught with uncertainty, necessitating novel alternative approaches. Our goal is to integrate in vitro liver experiments with agent-based cellular models to simulate a spatially extended hepatic lobule. Here we describe a graphical model of the sinusoidal network that efficiently simulates portal to centrilobular mass transfer in the hepatic lobule. We analyzed the effects of vascular topology and metabolism on the cell-level distribution following oral exposure to chemicals. The spatial distribution of metabolically inactive chemicals was similar across different vascular networks and a baseline well-mixed compartment. When chemicals were rapidly metabolized, concentration heterogeneity of the parent compound increased across the vascular network. As a result, our spatially extended lobule generated greater variability in dose-dependent cellular responses, in this case apoptosis, than were observed in the classical well-mixed liver or in a parallel tubes model. The mass-balanced graphical approach to modeling the hepatic lobule is computationally efficient for simulating long-term exposure, modular for incorporating complex cellular interactions, and flexible for dealing with evolving tissues