TY - JOUR A1 - Scheer, Nico A1 - Wilson, Ian D. T1 - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity JF - Drug Discovery Today N2 - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives. Y1 - 2016 U6 - https://doi.org/10.1016/j.drudis.2015.09.002 SN - 1359-6446 VL - 21 IS - 2 SP - 250 EP - 263 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - https://doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - https://doi.org/10.3109/03602532.2012.738687 SN - 1097-9883 IS - 1 SP - 110 EP - 121 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Henderson, Colin J. A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man JF - Expert Review of Clinical Pharmacology Y1 - 2009 U6 - https://doi.org/10.1586/17512433.2.2.105 SN - 1751-2441 VL - 2 IS - 2 SP - 105 EP - 109 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior JF - Drug Metabolism Reviews Y1 - 2009 U6 - https://doi.org/10.1080/03602530802605040 SN - 1097-9883 VL - 41 IS - 1 SP - 27 EP - 65 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity JF - Drug Metabolism Reviews Y1 - 2006 U6 - https://doi.org/10.1080/03602530600786232 SN - 1097-9883 VL - 38 IS - 3 SP - 515 EP - 597 ER - TY - JOUR A1 - Dadfar, Dryed Mohammadali A1 - Camozzi, Denise A1 - Darguzyte, Milita A1 - Roemhild, Karolin A1 - Varvarà, Paola A1 - Metselaar, Josbert A1 - Banala, Srinivas A1 - Straub, Marcel A1 - Güver, Nihan A1 - Engelmann, Ulrich M. A1 - Slabu, Ioana A1 - Buhl, Miriam A1 - Leusen, Jan van A1 - Kögerler, Paul A1 - Hermanns-Sachweh, Benita A1 - Schulz, Volkmar A1 - Kiessling, Fabian A1 - Lammers, Twan T1 - Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance JF - Journal of Nanobiotechnology N2 - Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications. Y1 - 2020 U6 - https://doi.org/10.1186/s12951-020-0580-1 SN - 1477-3155 VL - 18 IS - Article number 22 SP - 1 EP - 13 PB - Nature Portfolio ER - TY - JOUR A1 - Slabu, Ioana A1 - Roeth, Anjali A. A1 - Engelmann, Ulrich M. A1 - Wiekhorst, Frank A1 - Buhl, Eva M. A1 - Neumann, Ulf P. A1 - Schmitz-Rode, Thomas T1 - Modeling of magnetoliposome uptake in human pancreatic tumor cells in vitro JF - Nanotechnology Y1 - 2019 U6 - https://doi.org/10.1088/1361-6528/ab033e SN - 1361-6528 VL - 30 IS - 18 SP - 184004 ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Shasha, Carolyn A1 - Teeman, Eric A1 - Slabu, Iona A1 - Krishnan, Kannan M. T1 - Predicting size-dependent heating efficiency of magnetic nanoparticles from experiment and stochastic Néel-Brown Langevin simulation JF - Journal of Magnetism and Magnetic Materials Y1 - 2019 U6 - https://doi.org/10.1016/j.jmmm.2018.09.041 SN - 0304-8853 VL - 471 IS - 1 SP - 450 EP - 456 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Seifert, Julian A1 - Mues, Benedikt A1 - Roitsch, Stefan A1 - Ménager, Christine A1 - Schmidt, Annette M. A1 - Slabu, Ioana T1 - Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels JF - Journal of Magnetism and Magnetic Materials Y1 - 2019 U6 - https://doi.org/10.1016/j.jmmm.2018.09.113 SN - 0304-8853 VL - 471 IS - 1 SP - 486 EP - 494 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Roeth, Anjali A.J. A1 - Eberbeck, Dietmar A1 - Buhl, Eva Miriam A1 - Neumann, Ulf Peter A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells JF - Scientific Reports N2 - Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells. Y1 - 2018 U6 - https://doi.org/10.1038/s41598-018-31553-9 SN - 2045-2322 VL - 8 IS - 1 SP - Article number 13210 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Buhl, Eva Miriam A1 - Draack, Sebastian A1 - Viereck, Thilo A1 - Frank, A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Magnetic relaxation of agglomerated and immobilized iron oxide nanoparticles for hyperthermia and imaging applications JF - IEEE Magnetic Letters N2 - Magnetic nanoparticles (MNPs) are used as therapeutic and diagnostic agents for local delivery of heat and image contrast enhancement in diseased tissue. Besides magnetization, the most important parameter that determines their performance for these applications is their magnetic relaxation, which can be affected when MNPs immobilize and agglomerate inside tissues. In this letter, we investigate different MNP agglomeration states for their magnetic relaxation properties under excitation in alternating fields and relate this to their heating efficiency and imaging properties. With focus on magnetic fluid hyperthermia, two different trends in MNP heating efficiency are measured: an increase by up to 23% for agglomerated MNP in suspension and a decrease by up to 28% for mixed states of agglomerated and immobilized MNP, which indicates that immobilization is the dominant effect. The same comparatively moderate effects are obtained for the signal amplitude in magnetic particle spectroscopy. Y1 - 2018 U6 - https://doi.org/10.1109/LMAG.2018.2879034 SN - 1949-307X VL - 9 IS - Article number 8519617 PB - IEEE CY - New York, NY ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Buhl, Eva Miriam A1 - Baumann, Martin A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Agglomeration of magnetic nanoparticles and its effects on magnetic hyperthermia JF - Current Directions in Biomedical Engineering Y1 - 2017 U6 - https://doi.org/10.1515/cdbme-2017-0096 SN - 2364-5504 VL - 3 IS - 2 SP - 457 EP - 460 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Chen, Chao A1 - Jost, Peter A1 - Volker, Hanno A1 - Kaminski, Marvin A1 - Wirtssohn, Matti R. A1 - Engelmann, Ulrich M. A1 - Krüger, K. A1 - Schlich, Franziska F. A1 - Schlockermann, Carl A1 - Lobo, Ricardo P.S.M. A1 - Wuttig, Matthias T1 - Dielectric properties of amorphous phase-change materials JF - Physical Review B Y1 - 2017 U6 - https://doi.org/10.1103/PhysRevB.95.094111 SN - 2469-9950 VL - 95 IS - 9 SP - Article number 094111 ER - TY - JOUR A1 - Dantism, Shahriar A1 - Röhlen, Desiree A1 - Wagner, Torsten A1 - Wagner, P. A1 - Schöning, Michael Josef T1 - A LAPS-based differential sensor for parallelized metabolism monitoring of various bacteria JF - Sensors N2 - Monitoring the cellular metabolism of bacteria in (bio)fermentation processes is crucial to control and steer them, and to prevent undesired disturbances linked to metabolically inactive microorganisms. In this context, cell-based biosensors can play an important role to improve the quality and increase the yield of such processes. This work describes the simultaneous analysis of the metabolic behavior of three different types of bacteria by means of a differential light-addressable potentiometric sensor (LAPS) set-up. The study includes Lactobacillus brevis, Corynebacterium glutamicum, and Escherichia coli, which are often applied in fermentation processes in bioreactors. Differential measurements were carried out to compensate undesirable influences such as sensor signal drift, and pH value variation during the measurements. Furthermore, calibration curves of the cellular metabolism were established as a function of the glucose concentration or cell number variation with all three model microorganisms. In this context, simultaneous (bio)sensing with the multi-organism LAPS-based set-up can open new possibilities for a cost-effective, rapid detection of the extracellular acidification of bacteria on a single sensor chip. It can be applied to evaluate the metabolic response of bacteria populations in a (bio)fermentation process, for instance, in the biogas fermentation process. Y1 - 2019 U6 - https://doi.org/10.3390/s19214692 SN - 1424-8220 VL - 19 IS - 21 PB - MDPI CY - Basel ER - TY - JOUR A1 - Karschuck, T. L. A1 - Filipov, Y. A1 - Bollella, P. A1 - Schöning, Michael Josef A1 - Katz, E. T1 - Not-XOR (NXOR) logic gate based on an enzyme-catalyzed reaction JF - International Journal of Unconventional Computing N2 - Enzyme-catalyzed reactions have been designed to mimic various Boolean logic gates in the general framework of unconventional biomolecular computing. While some of the logic gates, particularly OR, AND, are easy to realize with biocatalytic reactions and have been reported in numerous publications, some other, like NXOR, are very challenging and have not been realized yet with enzyme reactions. The paper reports on a novel approach to mimicking the NXOR logic gate using the bell-shaped enzyme activity dependent on pH values. Shifting pH from the optimum value to the acidic or basic values by using acid or base inputs (meaning 1,0 and 0,1 inputs) inhibits the enzyme reaction, while keeping the optimum pH (assuming 0,0 and 1,1 input combinations) preserves a high enzyme activity. The challenging part of the present approach is the selection of an enzyme with a well-demonstrated bell-shape activity dependence on the pH value. While many enzymes can satisfy this condition, we selected pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase as this enzyme has the optimum pH center-located on the pH scale allowing the enzyme activity change by the acidic and basic pH shift from the optimum value corresponding to the highest activity. The present NXOR gate is added to the biomolecular “toolbox” as a new example of Boolean logic gates based on enzyme reactions. Y1 - 2019 SN - 1548-7199 VL - 14 IS - 3-4 SP - 235 EP - 242 PB - Old City Publishing CY - Philadelphia ER - TY - JOUR A1 - Kreyer, Jörg A1 - Müller, Marvin A1 - Esch, Thomas T1 - A Calculation Methodology for Predicting Exhaust Mass Flows and Exhaust Temperature Profiles for Heavy-Duty Vehicles JF - SAE International Journal of Commercial Vehicles N2 - The predictive control of commercial vehicle energy management systems, such as vehicle thermal management or waste heat recovery (WHR) systems, are discussed on the basis of information sources from the field of environment recognition and in combination with the determination of the vehicle system condition. In this article, a mathematical method for predicting the exhaust gas mass flow and the exhaust gas temperature is presented based on driving data of a heavy-duty vehicle. The prediction refers to the conditions of the exhaust gas at the inlet of the exhaust gas recirculation (EGR) cooler and at the outlet of the exhaust gas aftertreatment system (EAT). The heavy-duty vehicle was operated on the motorway to investigate the characteristic operational profile. In addition to the use of road gradient profile data, an evaluation of the continuously recorded distance signal, which represents the distance between the test vehicle and the road user ahead, is included in the prediction model. Using a Fourier analysis, the trajectory of the vehicle speed is determined for a defined prediction horizon. To verify the method, a holistic simulation model consisting of several hierarchically structured submodels has been developed. A map-based submodel of a combustion engine is used to determine the EGR and EAT exhaust gas mass flows and exhaust gas temperature profiles. All simulation results are validated on the basis of the recorded vehicle and environmental data. Deviations from the predicted values are analyzed and discussed. Y1 - 2020 U6 - https://doi.org/10.4271/02-13-02-0009 SN - 1946-3928 VL - 13 IS - 2 SP - 129 EP - 143 PB - SAE International CY - Warrendale, Pa. ER - TY - JOUR A1 - Fagan, Andrew J. A1 - Bitz, Andreas A1 - Björkman-Burtscher, Isabella M. A1 - Collins, Christopher M. A1 - Kimbrell, Vera A1 - Raaijmakers, Alexander J. E. T1 - 7T MR Safety JF - Journal of Magnetic Resonance Imaging (JMRI) Y1 - 2021 U6 - https://doi.org/10.1002/jmri.27319 SN - 1522-2586 VL - 53 IS - 2 SP - 333 EP - 346 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Henriques, A. A1 - Jurado, B. A1 - Grieser, M. A1 - Denis-Petit, D. A1 - Chiron, T. A1 - Gaudefroy, L. A1 - Glorius, J. A1 - Langer, Christoph A1 - Litvinov, Yu. A. A1 - Mathieu, L. A1 - Meot, V. A1 - Perez-Sanchez, R. A1 - Pibernat, J. A1 - Reifarth, R. A1 - Roig, O. A1 - Thomas, B. A1 - Thomas, B. A. A1 - Thomas, J. C. A1 - Tsekhanovich, I. T1 - Indirect measurements of neutron cross-secti at heavy-ion storage rings JF - Journal of Physics: Conference Series N2 - Cross sections for neutron-induced reactions of short-lived nuclei are essential for nuclear astrophysics since these reactions in the stars are responsible for the production of most heavy elements in the universe. These reactions are also key in applied domains like energy production and medicine. Nevertheless, neutron-induced cross-section measurements can be extremely challenging or even impossible to perform due to the radioactivity of the targets involved. Indirect measurements through the surrogate-reaction method can help to overcome these difficulties. The surrogate-reaction method relies on the use of an alternative reaction that will lead to the formation of the same excited nucleus as in the neutron-induced reaction of interest. The decay probabilities (for fission, neutron and gamma-ray emission) of the nucleus produced via the surrogate reaction allow one to constrain models and the prediction of the desired neutron cross sections. We propose to perform surrogate reaction measurements in inverse kinematics at heavy-ion storage rings, in particular at the CRYRING@ESR of the GSI/FAIR facility. We present the conceptual idea of the most promising setup to measure for the first time simultaneously the fission, neutron and gamma-ray emission probabilities. The results of the first simulations considering the 238U(d,d') reaction are shown, as well as new technical developments that are being carried out towards this set-up. Y1 - 2020 U6 - https://doi.org/10.1088/1742-6596/1668/1/012019 VL - 1668 IS - Art. 012019 PB - IOP CY - Bristol ER - TY - JOUR A1 - Varga, Laszlo A1 - Davinson, Thomas A1 - Glorius, Jan A1 - Jurado, Beatrix A1 - Langer, Christoph A1 - Lederer-Woods, Claudia A1 - Litvinov, Yuri A. A1 - Reifarth, Rene A1 - Slavkovska, Zuzana A1 - Stöhlker, Thomas A1 - Woods, Phil J. A1 - Xing, Yuan Ming T1 - Towards background-free studies of capture reaction in a heavy-ion storage ring JF - Journal of Physics: Conference Series N2 - Stored and cooled, highly-charged ions offer unprecedented capabilities for precision studies in the realm of atomic, nuclear structure and astrophysics[1]. After the successful investigation of the 96Ru(p,7)97Rh reaction cross section in 2009[2], the first measurement of the 124Xe(p,7)125Cs reaction cross section has been performed with decelerated, fully-ionized 124Xe ions in 2016 at the Experimental Storage Ring (ESR) of GSI[3]. Using a Double Sided Silicon Strip Detector, introduced directly into the ultra-high vacuum environment of a storage ring, the 125Cs proton-capture products have been successfully detected. The cross section has been measured at 5 different energies between 5.5AMeV and 8AMeV, on the high energy tail of the Gamow-window for hot, explosive scenarios such as supernovae and X-ray binaries. The elastic scattering on the H2 gas jet target is the major source of background to count the (p,7) events. Monte Carlo simulations show that an additional slit system in the ESR in combination with the energy information of the Si detector will enable background free measurements of the proton-capture products. The corresponding hardware is being prepared and will increase the sensitivity of the method tremendously. Y1 - 2020 VL - 1668 IS - Art 012046 PB - IOP CY - Bristol ER -