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Welden, Rene ; Jablonski, Melanie ; Wege, Christina ; Keusgen, Michael ; Wagner, Patrick Hermann ; Wagner, Torsten ; Schöning, Michael Josef
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.
Welden, Rene ; Nagamine Komesu, Cindy A. ; Wagner, Patrick H. ; Schöning, Michael Josef ; Wagner, Torsten
Photoelectrochemical (PEC) biosensors are a rather novel type of biosensors thatutilizelighttoprovideinformationaboutthecompositionofananalyte,enablinglight-controlled multi-analyte measurements. For enzymatic PEC biosensors,amperometric detection principles are already known in the literature. In con-trast, there is only a little information on H+-ion sensitive PEC biosensors. Inthis work, we demonstrate the detection of H+ions emerged by H+-generatingenzymes, exemplarily demonstrated with penicillinase as a model enzyme on atitanium dioxide photoanode. First, we describe the pH sensitivity of the sensorand study possible photoelectrocatalytic reactions with penicillin. Second, weshow the enzymatic PEC detection of penicillin.
In lab-on-chip systems, electrodes are important for the manipulation (e.g., cell stimulation, electrolysis) within such systems. An alternative to commonly used electrode structures can be a light-addressable electrode. Here, due to the photoelectric effect, the conducting area can be adjusted by modification of the illumination area which enables a flexible control of the electrode. In this work, titanium dioxide based light-addressable electrodes are fabricated by a sol–gel technique and a spin-coating process, to deposit a thin film on a fluorine-doped tin oxide glass. To characterize the fabricated electrodes, the thickness, and morphological structure are measured by a profilometer and a scanning electron microscope. For the electrochemical behavior, the dark current and the photocurrent are determined for various film thicknesses. For the spatial resolution behavior, the dependency of the photocurrent while changing the area of the illuminated area is studied. Furthermore, the addressing of single fluid compartments in a three-chamber system, which is added to the electrode, is demonstrated.
In this review article, we are going to present an overview on possible applications of light-addressable electrodes (LAE) as actuator/manipulation devices besides classical electrode structures. For LAEs, the electrode material consists of a semiconductor. Illumination with a light source with the appropiate wavelength leads to the generation of electron-hole pairs which can be utilized for further photoelectrochemical reaction. Due to recent progress in light-projection technologies, highly dynamic and flexible illumination patterns can be generated, opening new possibilities for light-addressable electrodes. A short introduction on semiconductor–electrolyte interfaces with light stimulation is given together with electrode-design approaches. Towards applications, the stimulation of cells with different electrode materials and fabrication designs is explained, followed by analyte-manipulation strategies and spatially resolved photoelectrochemical deposition of different material types.
Wendlandt, Tim ; Koch, Claudia ; Britz, Beate ; Liedek, Anke ; Schmidt, Nora ; Werner, Stefan ; Gleba, Yuri ; Vahidpour, Farnoosh ; Welden, Melanie ; Poghossian, Arshak ; Schöning, Michael Josef
Immunosorbent turnip vein clearing virus (TVCV) particles displaying the IgG-binding domains D and E of Staphylococcus aureus protein A (PA) on every coat protein (CP) subunit (TVCVPA) were purified from plants via optimized and new protocols. The latter used polyethylene glycol (PEG) raw precipitates, from which virions were selectively re-solubilized in reverse PEG concentration gradients. This procedure improved the integrity of both TVCVPA and the wild-type subgroup 3 tobamovirus. TVCVPA could be loaded with more than 500 IgGs per virion, which mediated the immunocapture of fluorescent dyes, GFP, and active enzymes. Bi-enzyme ensembles of cooperating glucose oxidase and horseradish peroxidase were tethered together on the TVCVPA carriers via a single antibody type, with one enzyme conjugated chemically to its Fc region, and the other one bound as a target, yielding synthetic multi-enzyme complexes. In microtiter plates, the TVCVPA-displayed sugar-sensing system possessed a considerably increased reusability upon repeated testing, compared to the IgG-bound enzyme pair in the absence of the virus. A high coverage of the viral adapters was also achieved on Ta2O5 sensor chip surfaces coated with a polyelectrolyte interlayer, as a prerequisite for durable TVCVPA-assisted electrochemical biosensing via modularly IgG-assembled sensor enzymes.
Wendorff, Marion ; Eggert, Thorsten ; Pohl, Martina ; Dresen, Carola ; Müller, Michael ; Jaeger, Karl-Erich ; Sprenger, Georg A. ; Schürmann, Melanie ; Schürmann, Martin ; Johnen, Sandra ; Sprenger, Gerda ; Sahm, Hermann ; Inoue, Tomoyuki ; Schörken, Ulrich ; Breittaupt, Holger ; Frölich, Bettina ; Heim, Petra ; Iding, Hans ; Juchem, Bettina ; Siegert, Petra ; Kula, Maria-Regina ; Weckbecker, Andrea ; Hummel, Werner ; Fessner, Wolf-Dieter ; Elling, Lothar ; Wolberg, Michael ; Bode, Silke ; Feldmann, Ralf ; Geilenkirchen, Petra ; Schubert, Thomas ; Walter, Lydia ; Dünnwald, Thomas ; Demir, Ayhan S. ; Kolter-Jung, Doris ; Nitsche, Adam ; Dünkelmann, Pascal ; Cosp, Annabel ; Lingen, Bettina
Werfel, Stanislas ; Günthner, Roman ; Hapfelmeier, Alexander ; Hanssen, Henner ; Kotliar, Konstantin ; Heemann, Uwe ; Schmaderer, Christoph
Dynamic retinal vessel analysis (DVA) provides a non-invasive way to assess microvascular function in patients and potentially to improve predictions of individual cardiovascular (CV) risk. The aim of our study was to use untargeted machine learning on DVA in order to improve CV mortality prediction and identify corresponding response alterations.
Werkhausen, Amelie ; Albracht, Kirsten ; Cronin, Neil J ; Paulsen, Gøran ; Bojsen-Møller, Jens ; Seynnes, Olivier R
During rapid deceleration of the body, tendons buffer part of the elongation of the muscle-tendon unit (MTU), enabling safe energy dissipation via eccentric muscle contraction. Yet, the influence of changes in tendon stiffness within the physiological range upon these lengthening contractions is unknown. This study aimed to examine the effect of training-induced stiffening of the Achilles tendon on triceps surae muscle-tendon behavior during a landing task. Twenty-one male subjects were assigned to either a 10-week resistance-training program consisting of single-leg isometric plantarflexion (n = 11) or to a non-training control group (n = 10). Before and after the training period, plantarflexion force, peak Achilles tendon strain and stiffness were measured during isometric contractions, using a combination of dynamometry, ultrasound and kinematics data. Additionally, testing included a step-landing task, during which joint mechanics and lengths of gastrocnemius and soleus fascicles, Achilles tendon, and MTU were determined using synchronized ultrasound, kinematics and kinetics data collection. After training, plantarflexion strength and Achilles tendon stiffness increased (15 and 18%, respectively), and tendon strain during landing remained similar. Likewise, lengthening and negative work produced by the gastrocnemius MTU did not change detectably. However, in the training group, gastrocnemius fascicle length was offset (8%) to a longer length at touch down and, surprisingly, fascicle lengthening and velocity were reduced by 27 and 21%, respectively. These changes were not observed for soleus fascicles when accounting for variation in task execution between tests. These results indicate that a training-induced increase in tendon stiffness does not noticeably affect the buffering action of the tendon when the MTU is rapidly stretched. Reductions in gastrocnemius fascicle lengthening and lengthening velocity during landing occurred independently from tendon strain. Future studies are required to provide insight into the mechanisms underpinning these observations and their influence on energy dissipation.
Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task
(2017)
Werkhausen, Amelie ; Albracht, Kirsten ; Cronin, Neil J. ; Meier, Rahel ; Mojsen-Moeller, Jens ; Seynnes, Olivier R.
Werkhausen, Amelie ; Cronin, Neil J. ; Albracht, Kirsten ; Bojsen-Møller, Jens ; Seynnes, Olivier R.
Training-induced increase in Achilles tendon stiffness affects tendon strain pattern during running
(2019)
Werkhausen, Amelie ; Cronin, Neil J. ; Albracht, Kirsten ; Paulsen, Gøran ; Larsen, Askild V. ; Bojsen-Møller, Jens ; Seynnes, Olivier R.
Background
During the stance phase of running, the elasticity of the Achilles tendon enables the utilisation of elastic energy and allows beneficial contractile conditions for the triceps surae muscles. However, the effect of changes in tendon mechanical properties induced by chronic loading is still poorly understood. We tested the hypothesis that a training-induced increase in Achilles tendon stiffness would result in reduced tendon strain during the stance phase of running, which would reduce fascicle strains in the triceps surae muscles, particularly in the mono-articular soleus.
Methods
Eleven subjects were assigned to a training group performing isometric singleleg plantarflexion contractions three times per week for ten weeks, and another ten subjects formed a control group. Before and after the training period, Achilles tendon stiffness was estimated, and muscle-tendon mechanics were assessed during running at preferred speed using ultrasonography, kinematics and kinetics.
Results
Achilles tendon stiffness increased by 18% (P <0:01) in the training group, but the associated reduction in strain seen during isometric contractions was not statistically significant. Tendon elongation during the stance phase of running was similar after training, but tendon recoil was reduced by 30% (P <0:01), while estimated tendon force remained unchanged. Neither gastrocnemius medialis nor soleus fascicle shortening during stance was affected by training.
Discussion
These results show that a training-induced increase in Achilles tendon
stiffness altered tendon behaviour during running. Despite training-induced changes in tendon mechanical properties and recoil behaviour, the data suggest that fascicle shortening patterns were preserved for the running speed that we examined. The asymmetrical changes in tendon strain patterns supports the notion that simple inseries models do not fully explain the mechanical output of the muscle-tendon unit during a complex task like running.
The compliant nature of distal limb muscle-tendon units is traditionally considered suboptimal in explosive movements when positive joint work is required. However, during accelerative running, ankle joint net mechanical work is positive. Therefore, this study aims to investigate how plantar flexor muscle-tendon behavior is modulated during fast accelerations. Eleven female sprinters performed maximum sprint accelerations from starting blocks, while gastrocnemius muscle fascicle lengths were estimated using ultrasonography. We combined motion analysis and ground reaction force measurements to assess lower limb joint kinematics and kinetics, and to estimate gastrocnemius muscle-tendon unit length during the first two acceleration steps. Outcome variables were resampled to the stance phase and averaged across three to five trials. Relevant scalars were extracted and analyzed using one-sample and two-sample t-tests, and vector trajectories were compared using statistical parametric mapping. We found that an uncoupling of muscle fascicle behavior from muscle-tendon unit behavior is effectively used to produce net positive mechanical work at the joint during maximum sprint acceleration. Muscle fascicles shortened throughout the first and second steps, while shortening occurred earlier during the first step, where negative joint work was lower compared with the second step. Elastic strain energy may be stored during dorsiflexion after touchdown since fascicles did not lengthen at the same time to dissipate energy. Thus, net positive work generation is accommodated by the reuse of elastic strain energy along with positive gastrocnemius fascicle work. Our results show a mechanism of how muscles with high in-series compliance can contribute to net positive joint work.
Werner, Frederik ; Groebel, Simone ; Krumbe, Christoph ; Wagner, Torsten ; Selmer, Thorsten ; Yoshinobu, Tatsuo ; Baumann, Marcus ; Schöning, Michael Josef
Werner, Frederik ; Krumbe, Christoph ; Schumacher, Katharina ; Groebel, Simone ; Spelthahn, Heiko ; Stellberg, Michael ; Wagner, Torsten ; Yoshinobu, Tatsuo ; Selmer, Thorsten ; Keusgen, Michael ; Baumann, Marcus ; Schöning, Michael Josef
Werner, Frederik ; Miyamoto, Ko-ichiro ; Wagner, Torsten ; Schöning, Michael Josef ; Yoshinobu, Tatsuo
To study chemical and biological processes, spatially resolved determination of the concentrations of one or more analyte species is of distinct interest. With a light-addressable potentiometric sensor (LAPS), chemical images can be created, which visualize the concentration distribution above the sensor plate. One important challenge is to achieve a good lateral resolution in order to detect events that take place in a small and limited region. LAPS utilizes a focused light spot to address the measurement region. By moving this light spot along the semiconductor sensor plate, the concentration distribution can be observed. In this study, we show that utilizing a pulse as light excitation instead of a traditionally used continuously modulated light excitation, the lateral resolution can be improved by a factor of 6 or more.
Werner, Frederik ; Schusser, Sebastian ; Spalthahn, Heiko ; Wagner, Torsten ; Yoshinobu, Tatsuo ; Schöning, Michael Josef
A light-addressable potentiometric sensor (LAPS) can measure the concentration of one or several analytes at the sensor surface simultaneously in a spatially resolved manner. A modulated light pointer stimulates the semiconductor structure at the area of interest and a responding photocurrent can be read out. By simultaneous stimulation of several areas with light pointers of different modulation frequencies, the read out can be performed at the same time. With the new proposed controller electronic based on a field-programmable gate array (FPGA), it is possible to control the modulation frequencies, phase shifts, and light brightness of multiple light pointers independently and simultaneously. Thus, it is possible to investigate the frequency response of the sensor, and to examine the analyte concentration by the determination of the surface potential with the help of current/voltage curves and phase/voltage curves. Additionally, the ability to individually change the light intensities of each light pointer is used to perform signal correction.
Semiconductor-based chemical imaging sensors, like the light-addressable potentiometric sensor (LAPS) or the pH-imaging sensor based on a charge-coupled device (CCD), are becoming a powerful tool for label-free imaging of biological phenomena. We have proposed a polyion-based enzymatic membrane to develop an acetylcholine (ACh) imaging sensor for neural cell-activity observations. In this study, a CCD-type ACh-imaging sensor and a LAPS-type ACh-imaging sensor were fabricated and the prospect of both sensors was clarified by making a comparison of their basic characteristics.
Werner, Frederik ; Wagner, Torsten ; Miyamoto, Ko-ichiro ; Yoshinobu, Tatsuo ; Schöning, Michael Josef
Light-addressable potentiometric sensors (LAPS) are field-effect-based sensors. A modulated light source is used to define the particular measurement spot to perform spatially resolved measurements of chemical species and to generate chemical images. In this work, an organic-LED (OLED) display has been chosen as a light source. This allows high measurement resolution and miniaturisation of the system. A new developed driving method for the OLED display optimised for LAPS-based measurements is demonstrated. The new method enables to define modulation frequencies between 1 kHz and 16 kHz and hence, reduces the measurement time of a chemical image by a factor of 40 compared to the traditional addressing of an OLED display.
Werner, Frederik ; Wagner, Torsten ; Miyamoto, Ko-ichiro ; Yoshinobu, Tatsuo ; Schöning, Michael Josef
Light-addressable potentiometric sensors (LAPS) are semiconductor-based potentiometric sensors, with the advantage to detect the concentration of a chemical species in a liquid solution above the sensor surface in a spatially resolved manner. The addressing is achieved by a modulated and focused light source illuminating the semiconductor and generating a concentration-depending photocurrent. This work introduces a LAPS set-up that is able to monitor the electrical impedance in addition to the photocurrent. The impedance spectra of a LAPS structure, with and without illumination, as well as the frequency behaviour of the LAPS measurement are investigated. The measurements are supported by electrical equivalent circuits to explain the impedance and the LAPS-frequency behaviour. The work investigates the influence of different parameters on the frequency behaviour of the LAPS. Furthermore, the phase shift of the photocurrent, the influence of the surface potential as well as the changes of the sensor impedance will be discussed.
Glucose oxidase (GOx) is an enzyme frequently used in glucose biosensors. As increased temperatures can enhance the performance of electrochemical sensors, we investigated the impact of temperature pulses on GOx that was drop-coated on flattened Pt microwires. The wires were heated by an alternating current. The sensitivity towards glucose and the temperature stability of GOx was investigated by amperometry. An up to 22-fold increase of sensitivity was observed. Spatially resolved enzyme activity changes were investigated via scanning electrochemical microscopy. The application of short (<100 ms) heat pulses was associated with less thermal inactivation of the immobilized GOx than long-term heating.
Concept, scientific research and managerial applications of Provocative Coaching, according to the „Provocative Therapy“ of Prof. Dr. Frank Farrelly (University of Wisconsin, U.S.A) in terms of an application of the Provocative Communication Style in specific situations of practical leadership, especially in the role of a coach for their subordinates.
Many companies still conduct the worldwide management of people as if neither the external economic nor the internal structure of the firm had changed. The costs of cross-cultural failure, for individuals and their companies, are enormous: personal and family costs; financial, professional and emotional costs; costs to one’s career prospects, to one’s self-esteem, to one’s marriage and family. This scenario describes sufficiently the reason for learning “the art of crossing cultures” (Craig Storti). To this end, this research paper describes an innovative approach of cross-cultural training, following the didactical ideas of Kolb and Fry, the so-called 'experiential learning'.
Whitehead, Mark ; Öhlschläger, Peter ; Almajhdi, Fahad N. ; Alloza, Leonor ; Marzábal, Pablo ; Meyers, Ann E. ; Hitzeroth, Inga I. ; Rybicki, Edward P.
Wiegand, Sandra ; Dietrich, Sascha ; Hertel, Robert ; Bongaerts, Johannes ; Evers, Stefan ; Volland, Sonja ; Daniel, Rolf ; Liesegang, Heiko
Wiegand, Sandra ; Voigt, Birgit ; Albrecht, Dirk ; Bongaerts, Johannes ; Evers, Stefan ; Hecker, Michael ; Daniel, Rolf ; Liesegang, Heiko
This article describes an Internet of things (IoT) sensing device with a wireless interface which is powered by the energy-harvesting method of the Wiegand effect. The Wiegand effect, in contrast to continuous sources like photovoltaic or thermal harvesters, provides small amounts of energy discontinuously in pulsed mode. To enable an energy-self-sufficient operation of the sensing device with this pulsed energy source, the output energy of the Wiegand generator is maximized. This energy is used to power up the system and to acquire and process data like position, temperature or other resistively measurable quantities as well as transmit these data via an ultra-low-power ultra-wideband (UWB) data transmitter. A proof-of-concept system was built to prove the feasibility of the approach. The energy consumption of the system during start-up was analysed, traced back in detail to the individual components, compared to the generated energy and processed to identify further optimization options. Based on the proof of concept, an application prototype was developed.
In this article we describe an Internet-of-Things sensing device with a wireless interface which is powered by the oftenoverlooked harvesting method of the Wiegand effect. The sensor can determine position, temperature or other resistively measurable quantities and can transmit the data via an ultra-low power ultra-wideband (UWB) data transmitter. With this approach we can energy-self-sufficiently acquire, process, and wirelessly transmit data in a pulsed operation. A proof-of-concept system was built up to prove the feasibility of the approach. The energy consumption of the system is analyzed and traced back in detail to the individual components, compared to the generated energy and processed to identify further optimization options. Based on the proof-of-concept, an application demonstrator was developed. Finally, we point out possible use cases.
With the growing interest in small distributed sensors for the “Internet of Things”, more attention is being paid to energy harvesting techologies. Reducing or eliminating the need for external power sources or batteries make devices more self-sufficient, more reliable, and reduces maintenance requirements. The Wiegand effect is a proven technology for harvesting small amounts of electrical power from mechanical motion.
Wiesen, Sebastian ; Tippkötter, Nils ; Muffler, Kai ; Suck, Kirstin ; Sohling, Ulrich ; Ruf, Friedrich ; Ulber, Roland
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−.
Infused Thermal Solutions (ITS) introduces a method for passive thermal control to stabilize structural components thermally without active heating and cooling systems, but with phase change material (PCM) for thermal energy storage (TES), in combination with lattice - both embedded in additive manufactured functional structures. In this ITS follow-on paper a thermal model approach and associated predictions are presented, related on the ITS functional breadboards developed at FH Aachen. Predictive TES by PCM is provided by a specially developed ITS PCM subroutine, which is applicable in ESATAN. The subroutine is based on the latent heat storage (LHS) method to numerically embed thermo-physical PCM behavior. Furthermore, a modeling approach is introduced to numerically consider the virtual PCM/lattice nodes within the macro-encapsulated PCM voids of the double wall ITS design. Related on these virtual nodes, in-plane and out-of-plane conductive links are defined. The recent additive manufactured ITS breadboard series are thermally cycled in the thermal vacuum chamber, both with and without embedded PCM. Related on breadboard hardware tests, measurement results are compared with predictions and are subsequently correlated. The results of specific simulations and measurements are presented. Recent predictive results of star tracker analyses are also presented in ICES-2021-106, based on this ITS PCM subroutine.
Thermal Characterization of additive manufactured Integral Structures for Phase Change Applications
(2020)
“Infused Thermal Solutions” (ITS) introduces a method for passive thermal control to stabilize structural components thermally without active heating and cooling systems, by using phase change material (PCM) in combination with lattice – both embedded into an additive manufactured integral structure. The technology is currently under development. This paper presents the results of the thermal property measurements performed on additive manufactured ITS breadboards. Within the breadboard campaigns key characteristics of the additive manufactured specimens were derived: Mechanical parameters: specimen impermeability, minimum wall thickness, lattice structure, subsequent heat treatment. Thermal properties: thermo-optical surface properties of the additive manufactured raw material, thermal conductivity and specific heat capacity measurements. As a conclusion the paper introduces an overview of potential ITS hardware applications, expected to increase the thermal performance.
Wilming, Anja ; Begemann, Jens ; Kuhne, Stefan ; Regestein, Lars ; Bongaerts, Johannes ; Evers, Stefan ; Maurer, Karl-Heinz ; Büchs, Jochen
The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice
(2018)
Wilson, C. E. ; Dickie, A. P. ; Schreiter, K. ; Wehr, R. ; Wilson, E. M. ; Bial, J. ; Scheer, Nico ; Wilson, I. D. ; Riley, R. J.
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.
The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice
(2017)
Wilson, Ian D. ; Wilson, Claire E. ; Scheer, Nico ; Dickie, A.P. ; Schreiter, K. ; Wilson, E. M. ; Riley, R. J. ; Wehr, R. ; Bial, J.
Winckler, Silvia ; Krueger, Rolf ; Schnitzler, Thomas ; Zang, Werner ; Fischer, Rainer ; Biselli, Manfred
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.
Windmüller, Anna ; Schaps, Kristian ; Zantis, Frederik ; Domgans, Anna ; Taklu, Bereket Woldegbreal ; Yang, Tingting ; Tsai, Chih-Long ; Schierholz, Roland ; Yu, Shicheng ; Kungl, Hans ; Tempel, Hermann ; Dunin-Borkowski, Rafal E. ; Hüning, Felix ; Hwang, Bing Joe ; Eichel, Rüdiger-A.
Ga-doped Li7La3Zr2O12 garnet solid electrolytes exhibit the highest Li-ion conductivities among the oxide-type garnet-structured solid electrolytes, but instabilities toward Li metal hamper their practical application. The instabilities have been assigned to direct chemical reactions between LiGaO2 coexisting phases and Li metal by several groups previously. Yet, the understanding of the role of LiGaO2 in the electrochemical cell and its electrochemical properties is still lacking. Here, we are investigating the electrochemical properties of LiGaO2 through electrochemical tests in galvanostatic cells versus Li metal and complementary ex situ studies via confocal Raman microscopy, quantitative phase analysis based on powder X-ray diffraction, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, and electron energy loss spectroscopy. The results demonstrate considerable and surprising electrochemical activity, with high reversibility. A three-stage reaction mechanism is derived, including reversible electrochemical reactions that lead to the formation of highly electronically conducting products. The results have considerable implications for the use of Ga-doped Li7La3Zr2O12 electrolytes in all-solid-state Li-metal battery applications and raise the need for advanced materials engineering to realize Ga-doped Li7La3Zr2O12for practical use.