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Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.
The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
(2017)
Ian D. Wilson
; Claire E. Wilson
; Nico Scheer
; A.P. Dickie
; K. Schreiter
; E. M. Wilson
; R. J. Riley
; R. Wehr
; J. Bial
The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
(2018)
C. E. Wilson
; A. P. Dickie
; K. Schreiter
; R. Wehr
; E. M. Wilson
; J. Bial
; Nico Scheer
; I. D. Wilson
; R. J. Riley
The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.
Anja Wilming
; Jens Begemann
; Stefan Kuhne
; Lars Regestein
; Johannes Bongaerts
; Stefan Evers
; Karl-Heinz Maurer
; Jochen Büchs
Zur Synthese der Hühnerinsulin-A-Kette, I : Darstellung der Fragmente A1–8, A9–15, A1–7 und A8–15
(1979)
Adsorptive Vorbehandlung von Rohglycerin für die 1,3-Propandiol Fermentation mit Clostridium diolis
(2014)
Sebastian Wiesen
; Nils Tippkötter
; Kai Muffler
; Kirstin Suck
; Ulrich Sohling
; Nils Ruf
; Roland Ulber
Bei der Gewinnung von Fettsäuren aus Pflanzenölen, z. B. zur Herstellung von Biopolymeren, oder bei der Biodiesel- und Seifenproduktion, fällt Glycerin als Nebenprodukt an. Bei der Biokonversion dieses Rohstoffes zu 1,3-Propandiol wird der Produktionsorganismus Clostridium diolis durch Verunreinigungen im Rohglycerin gehemmt. Als inhibierende Substanzen konnten freie Fettsäuren identifiziert werden. Mithilfe eines adsorptiven Aufarbeitungsverfahrens ist es gelungen, die Fettsäuren zu entfernen und die Konversionseffizienz zu 1,3-Propandiol zu erhöhen.
Sebastian Wiesen
; Nils Tippkötter
; Kai Muffler
; Kirstin Suck
; Ulrich Sohling
; Friedrich Ruf
; Roland Ulber
Due to their anion exchange characteristics, layered double hydroxides (LDHs) are suitable for the detoxification of aqueous, fatty acid containing fermentation substrates. The aim of this study is to examine the adsorption mechanism, using crude glycerol from plant oil esterification as a model system. Changes in the intercalation structure in relation to the amount of fatty acids adsorbed are monitored by X-ray diffraction and infra-red spectroscopy. Additionally, calcination of LDH is investigated in order to increase the binding capacity for fatty acids. Our data propose that, at ambient temperature, fatty acids can be bound to the hydrotalcite by adsorption or in addition by intercalation, depending on fatty acid concentration. The adsorption of fatty acids from crude glycerol shows a BET-like behavior. Above a fatty acid concentration of 3.5 g L−1, intercalation of fatty acids can be shown by the appearance of an increased interlayer spacing. This observation suggests a two phase adsorption process. Calcination of LDHs allows increasing the binding capacity for fatty acids by more than six times, mainly by reduction of structural CO32−.
Lagerstabiles flüssiges Wasch- oder Reinigungsmittel enthaltend Proteasen [Offenlegungsschrift]
(2011)
Susanne Wieland
; Petra Siegert
; Astrid Spitz
; Karl-Heinz Maurer
; Timothy O'Connell
; Inken Prüser
; Marc-Steffen Schiedel
; Thomas Eiting
; Dorota Sendor-Müller
; Thorsten Bastigkeit
; Konstantin Benda
; Sven Müller
Sandra Wiegand
; Birgit Voigt
; Dirk Albrecht
; Johannes Bongaerts
; Stefan Evers
; Michael Hecker
; Rolf Daniel
; Heiko Liesegang
Sandra Wiegand
; Sascha Dietrich
; Robert Hertel
; Johannes Bongaerts
; Stefan Evers
; Sonja Volland
; Rolf Daniel
; Heiko Liesegang
Mark Whitehead
; Peter Öhlschläger
; Fahad N. Almajhdi
; Leonor Alloza
; Pablo Marzábal
; Ann E. Meyers
; Inga I. Hitzeroth
; Edward P. Rybicki
Frederik Werner
; Christoph Krumbe
; Katharina Schumacher
; Simone Groebel
; Heiko Spelthahn
; Michael Stellberg
; Torsten Wagner
; Tatsuo Yoshinobu
; Thorsten Selmer
; Michael Keusgen
; Marcus Baumann
; Michael Josef Schöning
Frederik Werner
; Simone Groebel
; Torsten Wagner
; Tatsuo Yoshinobu
; Thorsten Selmer
; Marcus Baumann
; Michael Josef Schöning
Bestimmung der metabolischen Aktivität von Mikroorganismen während des Biogasbildungsprozesses
(2009)
Frederik Werner
; Simone Groebel
; K. Schuhmacher
; Heiko Spelthahn
; Torsten Wagner
; Thorsten Selmer
; Marcus Baumann
; Michael Josef Schöning
Frederik Werner
; Simone Groebel
; Christoph Krumbe
; Torsten Wagner
; Thorsten Selmer
; Tatsuo Yoshinobu
; Marcus Baumann
; Michael Josef Schöning
Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task
(2017)
Amelie Werkhausen
; Kirsten Albracht
; Neil J. Cronin
; Rahel Meier
; Jens Mojsen-Moeller
; Olivier R. Seynnes
Marion Wendorff
; Thorsten Eggert
; Martina Pohl
; Carola Dresen
; Michael Müller
; Karl-Erich Jaeger
; Georg A. Sprenger
; Melanie Schürmann
; Martin Schürmann
; Sandra Johnen
; Gerda Sprenger
; Hermann Sahm
; Tomoyuki Inoue
; Ulrich Schörken
; Holger Breittaupt
; Bettina Frölich
; Petra Heim
; Hans Iding
; Bettina Juchem
; Petra Siegert
; Maria-Regina Kula
; Andrea Weckbecker
; Werner Hummel
; Wolf-Dieter Fessner
; Lothar Elling
; Michael Wolberg
; Silke Bode
; Ralf Feldmann
; Petra Geilenkirchen
; Thomas Schubert
; Lydia Walter
; Thomas Dünnwald
; Ayhan S. Demir
; Doris Kolter-Jung
; Adam Nitsche
; Pascal Dünkelmann
; Annabel Cosp
; Bettina Lingen
Rene Welden
; Melanie Jablonski
; Christina Wege
; Michael Keusgen
; Patrick Hermann Wagner
; Torsten Wagner
; Michael Josef Schöning
The feasibility of light-addressed detection and manipulation of pH gradients inside an electrochemical microfluidic cell was studied. Local pH changes, induced by a light-addressable electrode (LAE), were detected using a light-addressable potentiometric sensor (LAPS) with different measurement modes representing an actuator-sensor system. Biosensor functionality was examined depending on locally induced pH gradients with the help of the model enzyme penicillinase, which had been immobilized in the microfluidic channel. The surface morphology of the LAE and enzyme-functionalized LAPS was studied by scanning electron microscopy. Furthermore, the penicillin sensitivity of the LAPS inside the microfluidic channel was determined with regard to the analyte’s pH influence on the enzymatic reaction rate. In a final experiment, the LAE-controlled pH inhibition of the enzyme activity was monitored by the LAPS.
Melanie Welden
; Robin Severins
; Arshak Poghossian
; Christina Wege
; Johannes Bongaerts
; Petra Siegert
; Michael Keusgen
; Michael Josef Schöning
Acetoin and diacetyl have a major impact on the flavor of alcoholic beverages such as wine or beer. Therefore, their measurement is important during the fermentation process. Until now, gas chromatographic techniques have typically been applied; however, these require expensive laboratory equipment and trained staff, and do not allow for online monitoring. In this work, a capacitive electrolyte–insulator–semiconductor sensor modified with tobacco mosaic virus (TMV) particles as enzyme nanocarriers for the detection of acetoin and diacetyl is presented. The enzyme acetoin reductase from Alkalihalobacillus clausii DSM 8716ᵀ is immobilized via biotin–streptavidin affinity, binding to the surface of the TMV particles. The TMV-assisted biosensor is electrochemically characterized by means of leakage–current, capacitance–voltage, and constant capacitance measurements. In this paper, the novel biosensor is studied regarding its sensitivity and long-term stability in buffer solution. Moreover, the TMV-assisted capacitive field-effect sensor is applied for the detection of diacetyl for the first time. The measurement of acetoin and diacetyl with the same sensor setup is demonstrated. Finally, the successive detection of acetoin and diacetyl in buffer and in diluted beer is studied by tuning the sensitivity of the biosensor using the pH value of the measurement solution.