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 - PAT A1 - Artmann, Gerhard A1 - Linder, Peter A1 - Bayer, Robin A1 - Gossmann, Matthias T1 - Celldrum electrode arrangement for measuring mechanical stress [Patent of invention] N2 - The invention pertains to a CellDrum electrode arrangement for measuring mechanical stress, comprising a mechanical holder (1 ) and a non-conductive membrane (4), whereby the membrane (4) is at least partially fixed at its circumference to the mechanical holder (1), keeping it in place when the membrane (4) may bend due to forces acting on the membrane (4), the mechanical holder (1) and the membrane (4) forming a container, whereby the membrane (1) within the container comprises an cell- membrane compound layer or biological material (3) adhered to the deformable membrane 4 which in response to stimulation by an agent may exert mechanical stress to the membrane (4) such that the membrane bending stage changes whereby the container may be filled with an electrolyte, whereby an electric contact (2) is arranged allowing to contact said electrolyte when filled into to the container, whereby within a predefined geometry to the fixing of the membrane (4) an electrode (7) is arranged, whereby the electrode (7) is electrically insulated with respect to the electric contact (2) as well as said electrolyte, whereby mechanical stress due to an agent may be measured as a change in capacitance. Y1 - 2017 N1 - Patent auch unter EP3403090, CN109477828, US2019033245 und LU92948 veröffentlicht. PB - WIPO CY - Geneva 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 - CHAP A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Scheer, Nico ED - Woolf, Thomas F. T1 - The use of transgenic animals to study drug metabolism T2 - Handbook of Drug Metabolism. 2nd Edition Y1 - 2009 SN - 978-1-4200-7647-9 SP - 637 EP - 658 PB - Informa Healthcare CY - New York ER - TY - CHAP A1 - Wolf, C. Roland A1 - Kapelyukh, Yury A1 - Scheer, Nico A1 - Henderson, Colin J. ED - Wilson, Alan G. E. T1 - Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs N2 - The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic. Y1 - 2015 SN - 978-1-78262-778-4 U6 - http://dx.doi.org/10.1039/9781782622376-00152 SP - 152 EP - 176 PB - RSC Publ. CY - Cambridge ER - TY - CHAP A1 - Scheer, Nico A1 - Chu, Xiaoyan A1 - Salphati, Laurent A1 - Zamek-Gliszczynski, Maciej J. ED - Nicholls, Glynis T1 - Knockout and humanized animal models to study membrane transporters in drug development T2 - Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development Y1 - 2016 SN - 978-1-78262-379-3 U6 - http://dx.doi.org/10.1039/9781782623793-00298 SP - 298 EP - 332 PB - Royal Society of Chemistry CY - Cambridge ER - TY - CHAP A1 - Samuelsson, K. A1 - Scheer, Nico A1 - Wilson, I. A1 - Wolf, C.R. A1 - Henderson, C.J. ED - Chackalamannil, Samuel T1 - Genetically Humanized Animal Models T2 - Comprehensive Medicinal Chemistry III. 3rd Edition N2 - Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development. KW - Chimeric liver-humanized mice KW - Drug distribution KW - Drug metabolism KW - Toxicology KW - Knockout mice Y1 - 2017 SN - 978-0-12-803201-5 U6 - http://dx.doi.org/10.1016/B978-0-12-409547-2.12376-5 SP - 130 EP - 149 PB - Elsevier CY - Saint Louis 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 - TY - JOUR A1 - Scheer, Nico A1 - Mclaughlin, Lesley A. A1 - Rode, Anja A1 - MacLeod, Alastair Kenneth A1 - Henderson, Colin J. A1 - Wolf, Roland C. T1 - Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism JF - Drug Metabolism and Disposition N2 - In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057885 SN - 1521-009X VL - 42 IS - 6 SP - 1022 EP - 1030 PB - ASPET CY - Bethesda, Md. ER - TY - CHAP A1 - Eggert, Mathias T1 - Big Data Research - How to Structure the Changes of the Past Decade? T2 - The Art of Structuring N2 - In the past decade, many IS researchers focused on researching the phenomenon of Big Data. At the same time, the relevance of data protection gets more attention than ever before. In particular, since the enactment of the European General Data Protection Regulation in May 2018 Information Systems research should provide answers for protecting personal data. The article at hand presents a structuring framework for Big Data research outcome and the consideration of data protection. IS Researchers might use the framework in order to structure Big Data literature and to identify research gaps that should be addressed in the future. Y1 - 2019 SN - 978-3-030-06234-7 U6 - http://dx.doi.org/10.1007/978-3-030-06234-7_26 SP - 271 EP - 281 PB - Springer CY - Cham ER - TY - JOUR A1 - Vögele, Stefan A1 - Rübbelke, Dirk A1 - Govorukha, Kristina A1 - Grajewski, Matthias T1 - Socio-technical scenarios for energy-intensive industries: the future of steel production in Germany JF - Climatic Change Y1 - 2019 U6 - http://dx.doi.org/10.1007/s10584-019-02366-0 SN - 0165-0009 SP - 1 EP - 16 PB - Springer CY - Berlin ER - TY - JOUR A1 - Campen, R. A1 - Kowalski, Julia A1 - Lyons, W.B. A1 - Tulaczyk, S. A1 - Dachwald, Bernd A1 - Pettit, E. A1 - Welch, K. A. A1 - Mikucki, J.A. T1 - Microbial diversity of an Antarctic subglacial community and high‐resolution replicate sampling inform hydrological connectivity in a polar desert JF - Environmental Microbiology Y1 - 2019 U6 - http://dx.doi.org/10.1111/1462-2920.14607 SN - 1462-2920 IS - accepted article PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Lyons, W. Berry A1 - Mikucki, Jill A. A1 - German, Laura A. A1 - Welch, Kathleen A. A1 - Welch, Susan A. A1 - Gardener, Christopher B. A1 - Tulaczyk, Slawek M. A1 - Pettit, Erin C. A1 - Kowalski, Julia A1 - Dachwald, Bernd T1 - The Geochemistry of Englacial Brine from Taylor Glacier, Antarctica JF - Journal of Geophysical Research: Biogeosciences Y1 - 2019 U6 - http://dx.doi.org/10.1029/2018JG004411 SN - 2169-8961 PB - Wiley CY - Hoboken ER - TY - CHAP A1 - Franzen, Julian A1 - Stecken, Jannis A1 - Pfaff, Raphael A1 - Kuhlenkötter, Bernd T1 - Using the Digital Shadow for a Prescriptive Optimization of Maintenance and Operation : The Locomotive in the Context of the Cyber-Physical System T2 - Advances in Production, Logistics and Traffic N2 - In competition with other modes of transport, rail freight transport is looking for solutions to become more attractive. Short-term success can be achieved through the data-driven optimization of operations and maintenance as well as the application of novel strategies such as prescriptive maintenance. After introducing the concept of prescriptive maintenance, this paper aims to prove that vehicle-focused applications of this approach indeed have the potential to increase attractiveness. However, even greater advantages can be activated if data from the horizontal network of the vehicle is available. Drawing on the state of the art in research and technology in the field of cyber-physical systems (CPS) as well as digital twins and shadows, our work serves to design a system of systems for the horizontal interconnection of a rail vehicle and to conceptualize a draft for a digital twin of a locomotive. Y1 - 2019 SN - 978-3-030-13535-5 U6 - http://dx.doi.org/10.1007/978-3-030-13535-5_19 SP - 265 EP - 276 PB - Springer CY - Cham ER - TY - JOUR A1 - Funke, Harald A1 - Beckmann, Nils A1 - Abanteriba, Sylvester T1 - An overview on dry low NOx micromix combustor development for hydrogen-rich gas turbine applications JF - International Journal of Hydrogen Energy Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.ijhydene.2019.01.161 SN - 0360-3199 VL - 44 IS - 13 SP - 6978 EP - 6990 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Breuer, Lars A1 - Pilas, Johanna A1 - Guthmann, Eric A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Towards light-addressable flow control: responsive hydrogels with incorporated graphene oxide as laser-driven actuator structures within microfluidic channels JF - Sensor and Actuators B: Chemical Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.snb.2019.02.086 SN - 0925-4005 VL - 288 SP - 579 EP - 585 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Jung, Alexander A1 - Müller, Wolfram A1 - Staat, Manfred T1 - Optimization of the flight technique in ski jumping: the influence of wind Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.jbiomech.2019.03.023 IS - Early view PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Grundmann, Jan Thimo A1 - Bauer, Waldemar A1 - Borchers, Kai A1 - Dumont, Etienne A1 - Grimm, Christian D. A1 - Ho, Tra-Mi A1 - Jahnke, Rico A1 - Lange, Caroline A1 - Maiwald, Volker A1 - Mikulz, Eugen A1 - Quantius, Dominik A1 - Reershemius, Siebo A1 - Renger, Thomas A1 - Riemann, Johannes A1 - Sasaki, Kaname A1 - Seefeldt, Patric A1 - Spietz, Peter A1 - Spröwitz, Tom A1 - Toth, Norbert A1 - Wejmo, Elisabet A1 - Biele, Jens A1 - Krause, Christian A1 - Cerotti, Matteo A1 - Peloni, Alessandro A1 - Dachwald, Bernd T1 - Small Spacecraft Solar Sailing for Small Solar System Body Multiple Rendezvous and Landing T2 - 2018 IEEE Aerospace Conference : 3-10 March 2018 Y1 - 2018 SN - 978-1-5386-2014-4 ER - TY - JOUR A1 - Scheer, Nico A1 - Henderson, Colin James A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Mclaren, Aileen W. A1 - MacLeod, Alastair Kenneth A1 - Lin, De A1 - Wright, Jayne A1 - Stanley, Lesley A1 - Wolf, C. Roland T1 - An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials JF - Drug Metabolism and Disposition Y1 - 2019 U6 - http://dx.doi.org/10.1124/dmd.119.086397 IS - Early view ER - TY - JOUR A1 - Jan Thimo, Grundmann A1 - Bauer, Waldemar A1 - Biele, Jens A1 - Boden, Ralf A1 - Ceriotti, Matteo A1 - Cordero, Federico A1 - Dachwald, Bernd A1 - Dumont, Etienne A1 - Grimm, Christian D. A1 - Hercik, David T1 - Capabilities of Gossamer-1 derived small spacecraft solar sails carrying Mascot-derived nanolanders for in-situ surveying of NEAs JF - Acta Astronautica Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.actaastro.2018.03.019 SN - 0094-5765 VL - 156 IS - 3 SP - 330 EP - 362 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Götten, Falk A1 - Havermann, Marc A1 - Braun, Carsten A1 - Gomez, Francisco A1 - Bil, Cees T1 - On the Applicability of Empirical Drag Estimation Methods for Unmanned Air Vehicle Design Read More: https://arc.aiaa.org/doi/10.2514/6.2018-3192 T2 - 2018 Aviation Technology, Integration, and Operations Conference, AIAA AVIATION Forum Y1 - 2018 U6 - http://dx.doi.org/10.2514/6.2018-3192 SN - 1533-385X N1 - AIAA 2018-3192 SP - Article 3192 ER -