TY - JOUR A1 - Quittmann, Oliver J. A1 - Abel, Thomas A1 - Albracht, Kirsten A1 - Strüder, Heiko K. T1 - Reliability of muscular activation patterns and their alterations during incremental handcycling in able-bodied participants JF - Sports Biomechanics Y1 - 2019 U6 - http://dx.doi.org/10.1080/14763141.2019.1593496 SN - 1752-6116 IS - Article in press PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Schildt, Ph. A1 - Braun, Carsten A1 - Marzocca, P. T1 - Metric evaluating potentials of condition-monitoring approaches for hybrid electric aircraft propulsion systems JF - CEAS Aeronautical Journal Y1 - 2019 U6 - http://dx.doi.org/10.1007/s13272-019-00411-3 SN - 1869-5590 SP - 1 EP - 14 PB - Springer CY - Berlin ER - TY - JOUR A1 - Capri, Miriam A1 - Morsiani, Cristina A1 - Santoro, Aurelia A1 - Moriggi, Manuela A1 - Conte, Maria A1 - Martucci, Morena A1 - Bellavista, Elena A1 - Fabbri, Cristina A1 - Giampieri, Enrico A1 - Albracht, Kirsten A1 - Flück, Martin A1 - Ruoss, Severin A1 - Brocca, Lorenza A1 - Canepari, Monica A1 - Longa, Emanuela A1 - Giulio, Irene Di A1 - Bottinelli, Roberto A1 - Cerretelli, Paolo A1 - Salvioli, Stefano A1 - Gelfi, Cecilia A1 - Franceschi, Claudio A1 - Narici, Marco A1 - Rittweger, Jörn T1 - Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Y1 - 2019 U6 - http://dx.doi.org/10.1096/fj.201801625R VL - 33 IS - 4 SP - 5168 EP - 5180 ER - TY - JOUR A1 - Bartella, Alexander K. A1 - Kamal, Mohammad A1 - Scholl, Ingrid A1 - Schiffer, Stefan A1 - Steegmann, Julius A1 - Ketelsen, Dominik A1 - Hölzle, Frank W. A1 - Lethaus, Bernd T1 - Virtual reality in preoperative imaging in maxillofacial surgery: implementation of “the next level”? JF - British Journal of Oral and Maxillofacial Surgery Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bjoms.2019.02.014 SN - 0266-4356 VL - 57 IS - 7 SP - 644 EP - 648 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Thoma, Andreas A1 - Ravi, Sridhar T1 - Significance of parallel computing on the performance of Digital Image Correlation algorithms in MATLAB N2 - Digital Image Correlation (DIC) is a powerful tool used to evaluate displacements and deformations in a non-intrusive manner. By comparing two images, one of the undeformed reference state of a specimen and another of the deformed target state, the relative displacement between those two states is determined. DIC is well known and often used for post-processing analysis of in-plane displacements and deformation of specimen. Increasing the analysis speed to enable real-time DIC analysis will be beneficial and extend the field of use of this technique. Here we tested several combinations of the most common DIC methods in combination with different parallelization approaches in MATLAB and evaluated their performance to determine whether real-time analysis is possible with these methods. To reflect improvements in computing technology different hardware settings were also analysed. We found that implementation problems can reduce the efficiency of a theoretically superior algorithm such that it becomes practically slower than a suboptimal algorithm. The Newton-Raphson algorithm in combination with a modified Particle Swarm algorithm in parallel image computation was found to be most effective. This is contrary to theory, suggesting that the inverse-compositional Gauss-Newton algorithm is superior. As expected, the Brute Force Search algorithm is the least effective method. We also found that the correct choice of parallelization tasks is crucial to achieve improvements in computing speed. A poorly chosen parallelisation approach with high parallel overhead leads to inferior performance. Finally, irrespective of the computing mode the correct choice of combinations of integerpixel and sub-pixel search algorithms is decisive for an efficient analysis. Using currently available hardware realtime analysis at high framerates remains an aspiration. Y1 - 2019 SP - 1 EP - 17 ER - TY - JOUR A1 - Bucur, Alexandru A1 - Lazarescu, Lucian A1 - Pop, Grigore Marian A1 - Achimas, Gheorghe A1 - Gebhardt, Andreas T1 - Tribological performance of biodegradable lubricants under different surface roughness of tools JF - Academic Journal of Manufacturing Engineering Y1 - 2019 SN - 1583-7904 VL - 17 IS - 1 SP - 172 EP - 178 ER - TY - JOUR A1 - Schwarz, Alexander A1 - Gebhardt, Andreas A1 - Schleser, Markus A1 - Popoola, Patricia T1 - New Welding Joint Geometries Manufactured by Powder Bed Fusion from 316L JF - Materials Performance and Characterization 8 Y1 - 2019 U6 - http://dx.doi.org/10.1520/MPC20180096 SN - 2379-1365 IS - in press ER - TY - JOUR A1 - Iken, Heiko A1 - Bronder, Thomas A1 - Goretzki, Alexander A1 - Kriesel, Jana A1 - Ahlborn, Kristina A1 - Gerlach, Frank A1 - Vonau, Winfried A1 - Zander, Willi A1 - Schubert, Jürgen A1 - Schöning, Michael Josef T1 - Development of a Combined pH- and Redox-Sensitive Bi-Electrode Glass Thin-Film Sensor JF - physica status solidi a : applications and materials sciences Y1 - 2019 U6 - http://dx.doi.org/10.1002/pssa.201900114 SN - 1862-6319 VL - 216 IS - 12 SP - 1 EP - 8 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Dantism, Shahriar A1 - Röhlen, Desiree A1 - Selmer, Thorsten A1 - Wagner, Torsten A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Quantitative differential monitoring of the metabolic activity of Corynebacterium glutamicum cultures utilizing a light-addressable potentiometric sensor system JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.111332 VL - 139 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Noureddine, Yacine A1 - Kraff, Oliver A1 - Ladd, Mark E. A1 - Wrede, Karsten A1 - Chen, Bixia A1 - Quick, Harald H. A1 - Schaefers, Georg A1 - Bitz, Andreas T1 - Radiofrequency induced heating around aneurysm clips using a generic birdcage head coil at 7 Tesla under consideration of the minimum distance to decouple multiple aneurysm clips JF - Magnetic Resonance in Medicine Y1 - 2019 U6 - http://dx.doi.org/10.1002/mrm.27835 SN - 1522-2594 IS - Early view SP - 1 EP - 17 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Valero, Daniel A1 - Chanson, Hubert A1 - Bung, Daniel B. T1 - Robust estimators for turbulence properties assessment Y1 - 2019 SP - 1 EP - 24 ER - TY - JOUR A1 - Gerhards, Michael A1 - Sander, Volker A1 - Zivkovic, Miroslav A1 - Belloum, Adam A1 - Bubak, Marian T1 - New approach to allocation planning of many‐task workflows on clouds JF - Concurrency and Computation: Practice and Experience N2 - Experience has shown that a priori created static resource allocation plans are vulnerable to runtime deviations and hence often become uneconomic or highly exceed a predefined soft deadline. The assumption of constant task execution times during allocation planning is even more unlikely in a cloud environment where virtualized resources vary in performance. Revising the initially created resource allocation plan at runtime allows the scheduler to react on deviations between planning and execution. Such an adaptive rescheduling of a many-task application workflow is only feasible, when the planning time can be handled efficiently at runtime. In this paper, we present the static low-complexity resource allocation planning algorithm (LCP) applicable to efficiently schedule many-task scientific application workflows on cloud resources of different capabilities. The benefits of the presented algorithm are benchmarked against alternative approaches. The benchmark results show that LCP is not only able to compete against higher complexity algorithms in terms of planned costs and planned makespan but also outperforms them significantly by magnitudes of 2 to 160 in terms of required planning time. Hence, LCP is superior in terms of practical usability where low planning time is essential such as in our targeted online rescheduling scenario. Y1 - 2020 U6 - http://dx.doi.org/10.1002/cpe.5404 SN - 1532-0634 VL - 32 IS - 2 Article e5404 SP - 1 EP - 16 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Kodomskoi, Leonid A1 - Kotliar, Konstantin A1 - Schröder, Andreas A1 - Weiss, Michael A1 - Hille, Konrad T1 - Suture-Probe Canaloplasty as an Alternative to Canaloplasty using the iTrack™ Microcatheter JF - Journal of Glaucoma Y1 - 2019 U6 - http://dx.doi.org/10.1097/IJG.0000000000001321 SN - 1057-0829 IS - Epub ahead of print PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Schopp, Christoph A1 - Britun, Nikolay A1 - Vorac, Jan A1 - Synek, Petr A1 - Snyders, Rony A1 - Heuermann, Holger T1 - Thermal and Optical Study on the Frequency Dependence of an Atmospheric Microwave Argon Plasma Jet JF - IEEE Transactions on Plasma Science Y1 - 2019 SN - 1939-9375 VL - 47 IS - 7 SP - 3176 EP - 3181 PB - IEEE CY - New York ER - TY - JOUR A1 - Reger, Vitali A1 - Kuhnhenne, Markus A1 - Hachul, Helmut A1 - Döring, Bernd A1 - Blanke, Tobias A1 - Göttsche, Joachim T1 - Plusenergiegebäude 2.0 in Stahlleichtbauweise JF - Stahlbau Y1 - 2019 U6 - http://dx.doi.org/10.1002/stab.201900034 SN - 1437-1049 (E-journal), 0038-9145 (print) VL - 88 IS - 6 SP - 522 EP - 528 PB - Ernst & Sohn CY - Berlin ER - TY - JOUR A1 - Kopp, Alexander A1 - Schmeets, Ralf A1 - Gosau, Martin A1 - Friedrich, Reinhard E. A1 - Fuest, Sandra A1 - Behbahani, Mehdi A1 - Barbeck, Mike A1 - Rutkowski, Rico A1 - Burg, Simon A1 - Kluwe, Lan A1 - Henningsen, Anders T1 - Production and Characterization of Porous Fibroin Scaffolds for Regenerative Medical Application JF - In Vivo Y1 - 2019 U6 - http://dx.doi.org/10.21873/invivo.11536 SN - 1791-7549 VL - 33 IS - 3 SP - 757 EP - 762 ER - TY - JOUR A1 - Stulpe, Werner T1 - Aspects of the Quantum-Classical Connection Based on Statistical Maps JF - Foundations of Physics Y1 - 2019 U6 - http://dx.doi.org/10.1007/s10701-019-00269-9 VL - 49 IS - 6 SP - 677 EP - 692 PB - Springer CY - Berlin ER - TY - JOUR A1 - Engel, Mareike A1 - Bayer, Hendrik A1 - Holtmann, Dirk A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Flavin secretion of Clostridium acetobutylicum in a bioelectrochemical system - Is an iron limitation involved? JF - Bioelectrochemistry Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bioelechem.2019.05.014 SN - 1567-5394 IS - In Press, Accepted Manuscript PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Claer, Mario A1 - Ferrein, Alexander A1 - Schiffer, Stefan T1 - Calibration of a Rotating or Revolving Platform with a LiDAR Sensor JF - Applied Sciences Y1 - 2019 U6 - http://dx.doi.org/10.3390/app9112238 SN - 2076-3417 VL - Volume 9 IS - issue 11, 2238 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - Combinatorial assembly of ferredoxin‐linked modules in Escherichia coli yields a testing platform for Rnf‐complexes JF - Biotechnology and Bioengineering Y1 - 2019 U6 - http://dx.doi.org/10.1002/bit.27079 IS - accepted article SP - 1 EP - 36 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Kapelyukh, Yury A1 - Henderson, Colin James A1 - Scheer, Nico A1 - Rode, Anja A1 - Wolf, Charles Roland T1 - Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice JF - Drug Metabolism and Disposition Y1 - 2019 U6 - http://dx.doi.org/10.1124/dmd.119.087718 IS - Early view ER - TY - JOUR A1 - Jochim, Haldor E. A1 - Menzel, Christoph J. T1 - Die Trassenbündelung als Planungsmethode nachhaltiger Verkehrspolitik JF - Der Eisenbahningenieur : EI Y1 - 2018 SN - 0013-2810 VL - 69 IS - 11 SP - 26 EP - 31 PB - DVV Media Group CY - Hamburg ER - TY - JOUR A1 - Poghossian, Arshak A1 - Geissler, Hanno A1 - Schöning, Michael Josef T1 - Rapid methods and sensors for milk quality monitoring and spoilage detection JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.04.040 SN - 0956-5663 VL - 140 IS - Article 111272 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Cornelis, Peter A1 - Givanoudi, Stella A1 - Yongabi, Derick A1 - Iken, Heiko A1 - Duwé, Sam A1 - Deschaume, Olivier A1 - Robbens, Johan A1 - Dedecker, Peter A1 - Bartic, Carmen A1 - Wübbenhorst, Michael A1 - Schöning, Michael Josef A1 - Heyndrickx, Marc A1 - Wagner, Patrick T1 - Sensitive and specific detection of E. coli using biomimetic receptors in combination with a modified heat-transfer method JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.04.026 SN - 0956-5663 VL - 136 SP - 97 EP - 105 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Meyer, Carolin A1 - Gaalen, Kerstin van A1 - Leschinger, Tim A1 - Scheyerer, Max J. A1 - Neiss, Wolfram F. A1 - Staat, Manfred A1 - Müller, Lars P. A1 - Wegmann, Kilian T1 - Kyphoplasty of Osteoporotic Fractured Vertebrae: A Finite Element Analysis about Two Types of Cement JF - BioMed Research International Y1 - 2019 U6 - http://dx.doi.org/10.1155/2019/9232813 SP - Article ID 9232813 ER - TY - JOUR A1 - Puppe, Michael A1 - Giuliano, Stefano A1 - Frantz, Cathy A1 - Uhlig, Ralf A1 - Schumacher, Ralph A1 - Ibraheem, Wagdi A1 - Schmalz, Stefan A1 - Waldmann, Barbara A1 - Guder, Christoph A1 - Peter, Dennis A1 - Schwager, Christian A1 - Teixeira Boura, Cristiano José A1 - Alexopoulos, Spiros A1 - Spiegel, Michael A1 - Wortmann, Jürgen A1 - Hinrichs, Matthias A1 - Engelhard, Manfred A1 - Aust, Michael T1 - Techno-economic optimization of molten salt solar tower plants JF - AIP Conference Proceedings art.no. 040033 N2 - In this paper the results of a techno-economic analysis of improved and optimized molten salt solar tower plants (MSSTP plants) are presented. The potential improvements that were analyzed include different receiver designs, different designs of the HTF-system and plant control, increased molten salt temperatures (up to 640°C) and multi-tower systems. Detailed technological and economic models of the solar field, solar receiver and high temperature fluid system (HTF-system) were developed and used to find potential improvements compared to a reference plant based on Solar Two technology and up-to-date cost estimations. The annual yield model calculates the annual outputs and the LCOE of all variants. An improved external tubular receiver and improved HTF-system achieves a significant decrease of LCOE compared to the reference. This is caused by lower receiver cost as well as improvements of the HTF-system and plant operation strategy, significantly reducing the plant own consumption. A novel star receiver shows potential for further cost decrease. The cavity receiver concepts result in higher LCOE due to their high investment cost, despite achieving higher efficiencies. Increased molten salt temperatures seem possible with an adapted, closed loop HTF-system and achieve comparable results to the original improved system (with 565°C) under the given boundary conditions. In this analysis all multi tower systems show lower economic viability compared to single tower systems, caused by high additional cost for piping connections and higher cost of the receivers. REFERENCES Y1 - 2019 U6 - http://dx.doi.org/10.1063/1.5067069 VL - 2033 IS - Issue 1 PB - AIP Publishing CY - Melville, NY ER - TY - JOUR A1 - Tran, Ngoc Trinh A1 - Staat, Manfred T1 - Direct plastic structural design under lognormally distributed strength by chance constrained programming JF - Optimization and Engineering N2 - We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements. Y1 - 2020 U6 - http://dx.doi.org/10.1007/s11081-019-09437-2 SN - 1573-2924 VL - 21 IS - 1 SP - 131 EP - 157 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Albanna, Walid A1 - Lüke, Jan Niklas A1 - Schubert, Gerrit Alexander A1 - Dibué-Adjei, Maxine A1 - Kotliar, Konstantin A1 - Hescheler, Jürgen A1 - Clusmann, Hans A1 - Steiger, Hans-Jakob A1 - Hänggi, Daniel A1 - Kamp, Marcel A. A1 - Schneider, Toni A1 - Neumaier, Felix T1 - Modulation of Ca v 2.3 channels by unconjugated bilirubin (UCB) – Candidate mechanism for UCB-induced neuromodulation and neurotoxicity JF - Molecular and Cellular Neuroscience Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.mcn.2019.03.003 SN - 1044-7431 VL - 96 IS - 4 SP - 35 EP - 46 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Rietsch, Stefan H. G. A1 - Brunheim, Sascha A1 - Orzada, Stephan A1 - Voelker, Maximilian N. A1 - Maderwald, Stefan A1 - Bitz, Andreas A1 - Gratz, Marcel A1 - Ladd, Mark E. A1 - Quick, Harald H. T1 - Development and evaluation of a 16-channel receive-only RF coil to improve 7T ultra-high field body MRI with focus on the spine JF - Magnetic Resonance in Medicine Y1 - 2019 U6 - http://dx.doi.org/10.1002/mrm.27731 SN - 1522-2594 IS - Early view PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Lempiäinen, Harri A1 - Couttet, Philippe A1 - Bolognani, Federico A1 - Müller, Arne A1 - Dubost, Valérie A1 - Luisier, Raphaëlle A1 - Rio-Espinola, Alberto del A1 - Vitry, Veronique A1 - Unterberger, Elif B. A1 - Thomson, John P. A1 - Treindl, Fridolin A1 - Metzger, Ute A1 - Wrzodek, Clemens A1 - Hahne, Florian A1 - Zollinger, Tulipan A1 - Brasa, Sarah A1 - Kalteis, Magdalena A1 - Marcellin, Magali A1 - Giudicelli, Fanny A1 - Braeuning, Albert A1 - Morawiec, Laurent A1 - Zamurovic, Natasa A1 - Längle, Ulrich A1 - Scheer, Nico A1 - Schübeler, Dirk A1 - Goodman, Jay A1 - Chibout, Salah-Dine A1 - Marlowe, Jennifer A1 - Theil, Dietlinde A1 - Heard, David J. A1 - Grenet, Olivier A1 - Zell, Andreas A1 - Templin, Markus F. A1 - Meehan, Richard R. A1 - Wolf, Roland C. A1 - Elcombe, Clifford R. A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Rémi A1 - Moggs, Jonathan G. T1 - Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion JF - Toxicological Sciences N2 - The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds. Y1 - 2012 U6 - http://dx.doi.org/10.1093/toxsci/kfs303 SN - 1094-2025 VL - 131 IS - 2 SP - 375 EP - 386 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Morais, Paulo V. A1 - Silva, Anielle C. A. A1 - Dantas, Noelio O. A1 - Schöning, Michael Josef A1 - Siqueira, José R., Jr. T1 - Hybrid Layer‐by‐Layer Film of Polyelectrolytes‐Embedded Catalytic CoFe2O4 Nanocrystals as Sensing Units in Capacitive Electrolyte‐Insulator‐Semiconductor Devices JF - physica status solidi a : applications and materials sciences Y1 - 2019 U6 - http://dx.doi.org/10.1002/pssa.201900044 VL - 216 IS - 1900044 SP - 1 EP - 9 PB - Wiley CY - Weinheim 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 - http://dx.doi.org/10.1080/03602530600786232 SN - 1097-9883 VL - 38 IS - 3 SP - 515 EP - 597 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 - http://dx.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 - 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 - http://dx.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 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - http://dx.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 - 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 - http://dx.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 - 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 - http://dx.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 - Campos-Ortega, José A. T1 - Use of the Gal4-UAS technique for targeted gene expression in the zebrafish JF - Mechanism of Development Y1 - 1999 U6 - http://dx.doi.org/10.1016/S0925-4773(98)00209-3 SN - 0925-4773 VL - 80 IS - 2 SP - 153 EP - 158 ER - TY - JOUR A1 - Halbach, Thorsten A1 - Scheer, Nico T1 - Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins JF - Nucleic Acids Research Y1 - 2000 U6 - http://dx.doi.org/10.1093/nar/28.18.3542 SN - 1362-4962 VL - 28 IS - 18 SP - 3542 EP - 3550 ER - TY - JOUR A1 - Scheer, Nico A1 - Groth, Anne A1 - Hans, Stefan A1 - Campos-Ortega, José A. T1 - An instructive function for Notch in promoting gliogenesis in the zebrafish retina JF - Development Y1 - 2001 SN - 0950-1991 VL - 128 IS - 7 SP - 1099 EP - 1107 ER - TY - JOUR A1 - Lawson, Nathan D. A1 - Scheer, Nico A1 - Pham, Van N. A1 - Kim, Ceol-Hee A1 - Chitnis, Ajay B. A1 - Campos-Ortega, José A. A1 - Weinstein, Brant M. T1 - Notch signaling is required for arterial-venous differentiation during embryonic vascular development JF - Development Y1 - 2001 SN - 1477-9129 VL - 128 IS - 19 SP - 3675 EP - 3683 ER - TY - JOUR A1 - Scheer, Nico A1 - Riedl, Iris A1 - Warren, J.T. A1 - Kuwada, John Y. A1 - Campos-Ortega, José A. T1 - A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish JF - Mechanism of Development Y1 - 2002 U6 - http://dx.doi.org/10.1016/S0925-4773(01)00621-9 SN - 0925-4773 VL - 112 IS - 1-2 SP - 9 EP - 14 ER - TY - JOUR A1 - Hans, Stefan A1 - Scheer, Nico A1 - Riedl, Iris A1 - Weizäcker, Elisabeth von A1 - Blader, Patrick A1 - Campos-Ortega, José A. T1 - her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling JF - Development Y1 - 2004 U6 - http://dx.doi.org/10.1242/dev.01167 SN - 1477-9129 VL - 131 IS - 12 SP - 2957 EP - 2969 ER - TY - JOUR A1 - Reugels, Alexander M. A1 - Boggetti, Barbara A1 - Scheer, Nico A1 - Campos-Ortega, José A. T1 - Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio JF - Developmental Dynamics Y1 - 2006 U6 - http://dx.doi.org/10.1002/dvdy.20699 SN - 1097-0177 VL - 235 IS - 4 SP - 934 EP - 948 ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - McEwan, Jillian A1 - Beuger, Vincent A1 - Stanley, Lesley A. A1 - Rode, Anja A1 - Wolf, C. Roland T1 - Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines JF - Molecular Pharmacology N2 - The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.111.075192 SN - 1521-0111 VL - 81 IS - 1 SP - 63 EP - 72 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Rode, Anja A1 - Zevnik, Branko A1 - Niehaves, Sandra A1 - Faust, Nicole A1 - Wolf, C. Roland T1 - A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response JF - Journal of Clinical Investigation Y1 - 2008 U6 - http://dx.doi.org/https://doi.org/10.1172/JCI35483 SN - 1558-8238 VL - 118 IS - 9 SP - 3228 EP - 3239 ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Wolf, C. Roland T1 - In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice JF - Drug Metabolism and Disposition N2 - Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound. Y1 - 2010 U6 - http://dx.doi.org/10.1124/dmd.109.031872 SN - 1521-009X VL - 38 IS - 7 SP - 1046 EP - 1053 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Ross, Jillian A1 - Plummer, Simon M. A1 - Rode, Anja A1 - Scheer, Nico A1 - Bower, Conrad C. A1 - Vogel, Ortwin A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Elcombe, Clifford R. T1 - Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo JF - Toxicological Sciences N2 - Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained. Y1 - 2010 U6 - http://dx.doi.org/10.1093/toxsci/kfq118 SN - 1096-0929 VL - 116 IS - 2 SP - 452 EP - 466 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Buechel, Sandra A1 - Wolf, C. Roland T1 - Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines JF - Molecular Pharmacology N2 - Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.112.080036 SN - 1521-0111 VL - 82 IS - 6 SP - 1022 EP - 1029 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Balimane, Praveen A1 - Hayward, Michael D. A1 - Buechel, Sandra A1 - Kauselmann, Gunther A1 - Wolf, C. Roland T1 - Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line JF - Drug Metabolism and Disposition N2 - The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2. Y1 - 2012 U6 - http://dx.doi.org/10.1124/dmd.112.047605 SN - 1521-0111 VL - 40 IS - 11 SP - 2212 EP - 2218 PB - ASPET CY - Bethesda, Md. ER -