In this paper an overview of optimal adaptive control of (bio)chemical reactors is presented. Following the paradigm of the Minimum Principle of Pontryagin the derivation of optimal control sequences for fed-batch production processes is briefly revisited. Next, it is illustrated how the obtained optimal profiles can be exploited in the characterization of nearly optimal control sequences in terms of the qualitative behavior of the specific growth and production rates as function of the limiting substrates. Implementing this knowledge leads in a natural way to the design of (nearly) optimal adaptive feedback controllers. Special emphasis will lie on the potential of on-line biomass measurements (obtained with the Biomass Monitor) in the estimation algorithm of the growth kinetics being the adaptive component of the controller. Extensions towards fermentation processes with (i) multiple substrates and (ii) non-monotonic kinetics are also included. Finally, perspectives towards optimal adaptive control of not perfectly mixed (bio)chemical reactor systems, such as chemical tubular reactors, are outlined.

In ischemic or hypoxic tissues, elevated Ca2+ levels have emerged as one of the main damaging agents among other Ca2+-independent mechanisms of cellular injury. Because mitochondria, besides the endoplasmic reticulum, play a key role in the maintainance of cellular Ca2+ homeostasis, alterations in the mitochondrial Ca2+ content ([Ca2+]m) were monitored in addition to changes in cytosolic Ca2+ concentration ([Ca2+]i) during metabolic inhibition (MI) in renal epithelial Madin-Darby canine kidney (MDCK) cells. [Ca2+]i and [Ca2+]m were monitored via, respectively, fura 2 and rhod 2 measurements. MI induced an increase in [Ca2+]i reaching 631+/-78 nM in approximately 20 min, followed by a decrease to 118+/-9 nM in the next approximately 25 min. A pronounced drop in cellular ATP levels and a rapid increase in intracellular Na+ concentrations in the first 20 min of MI excluded Ca2+ efflux in the second phase via plasma membrane ATPases or Na+/Ca2+ exchangers (NCE). Mitochondrial rhod 2 intensities increased to 434+/-46% of the control value during MI, indicating that mitochondria sequester Ca2+ during MI. The mitochondrial potential (deltapsim) was lost in 20 min of MI, excluding mitochondrial Ca2+ uptake via the deltapsim-dependent mitochondrial Ca2+ uniporter after 20 min of MI. Under Na+-free conditions, or when CGP-37157, a specific inhibitor of the mitochondrial NCE, was used, no drop in [Ca2+]i was seen during MI, whereas the MI-induced increase in mitochondrial rhod 2 fluorescence was strongly reduced. To our knowledge, this study is the first to report that in metabolically inhibited renal epithelial cells mitochondria take up Ca2+ via the NCE acting in the reverse mode.

Renal ischemia and subsequent reperfusion lead to changes in the regulation of hydrogen ions across the mitochondrial membrane. This study was designed to monitor pH changes in the cytosol and mitochondria of Madin-Darby Canine Kidney cells exposed to metabolic inhibition and subsequent recovery. A classical one-photon confocal imaging approach using the pH-sensitive fluorophore carboxy SNARF-1 was used to define specific loading, calibration, and correction procedures to obtain reliable cytosolic and mitochondrial pH values in living cells. Metabolic inhibition resulted in both cytosolic and mitochondrial acidification, with a more pronounced decrease of mitochondrial pH as compared to the cytosolic pH. Shortly after removing the metabolic inhibition, cytosolic pH did not recover, whereas mitochondrial pH slowly increased. Our method is applicable to other cell types provided that the mitochondria can be loaded with SNARF-1 and that the cells possess a mitochondria-free region to measure SNARF-1 in the cytosol.

Optimal heat exchanger temperature profiles of exothermic tubular reactors were determined under the assumption of steady‐state and plug‐flow characteristics. The minimum principle of Pontryagin (optimal control theory) was applied in a straightforward analytical sense. To enable a trade‐off between process performance and heat loss, a combined cost criterion was defined. In the first approach of specifying only terminal costs, the optimal control input was of the bang‐bang type that keeps the heat exchanger temperature constant at its maximum or minimum value. Afterwards, the terminal cost criterion was extended with an integral part that accounts for the global heat loss during the process. This integral cost part induced a control of the bang‐singular‐bang type. The desired performance can be met by selecting appropriate weights for terminal and integral costs.

Cholesterol synthesis and transport in oligodendrocytes are essential for optimal myelination and remyelination in pathological conditions such as multiple sclerosis. However, little is known about cholesterol homeostasis in the myelin-forming oligodendrocytes. Liver X receptors (LXRs) are nuclear oxysterol receptors that regulate genes involved in cholesterol homeostasis and may therefore play an important role in de- and remyelination. We investigated whether LXRs regulate cholesterol homeostasis in oligodendrocytes. mRNA expression of genes encoding LXR-α and LXR-β and their target genes (ABCA1, ABCG1, ABCG4, apoE, and LDLR) was detected in oligodendrocytes derived from both neonatal and adult rats using quantitative real-time PCR. The expression of LXR-β and several target genes was increased during oligodendrocyte differentiation. We further demonstrated that treatment of primary neonatal rat oligodendrocytes with the synthetic LXR agonist T0901317 induced the expression of several established LXR target genes, including ABCA1, ABCG1, apoE, and LDLR. Treatment of oligodendrocytes with T0901317 resulted in an enhanced cholesterol efflux in the presence of apolipoprotein A-I or high-density lipoprotein particles. These data show that LXRs are involved in regulating cholesterol homeostasis in oligodendrocytes.

This article describes a fully automatic image analysis procedure for fast and reliable characterization of the activated sludge composition, that is, the floc and filament features. The algorithms developed for each of the analysis steps, that is, segmentation, object recognition, and characterization, are described in detail. Although the application range of the recognition method is a priori expanded by introducing a number of control parameters, the procedure proves to be intrinsically robust as it produces satisfactory results for a fixed set of parameter values for a wide variety of image types.

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Many recent AD studies mistakenly link performance improvements exclusively to DIET.• Unequivocally proving the occurrence of DIET requires a complex set of methods.• This paper groups DIET characterization methods in four categories and discusses their strengths and weaknesses. • This paper presents promising DIET detection approaches that merit further exploration.