@article{ScheerBalimaneHaywardetal.2012, author = {Scheer, Nico and Balimane, Praveen and Hayward, Michael D. and Buechel, Sandra and Kauselmann, Gunther and Wolf, C. Roland}, title = {Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line}, series = {Drug Metabolism and Disposition}, volume = {40}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/dmd.112.047605}, pages = {2212 -- 2218}, year = {2012}, abstract = {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.}, language = {en} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {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.}, language = {en} } @incollection{Eggert2019, author = {Eggert, Mathias}, title = {Big Data Research - How to Structure the Changes of the Past Decade?}, series = {The Art of Structuring}, booktitle = {The Art of Structuring}, publisher = {Springer}, address = {Cham}, isbn = {978-3-030-06234-7}, doi = {10.1007/978-3-030-06234-7_26}, pages = {271 -- 281}, year = {2019}, abstract = {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.}, language = {en} } @article{VoegeleRuebbelkeGovorukhaetal.2019, author = {V{\"o}gele, Stefan and R{\"u}bbelke, Dirk and Govorukha, Kristina and Grajewski, Matthias}, title = {Socio-technical scenarios for energy-intensive industries: the future of steel production in Germany}, series = {Climatic Change}, journal = {Climatic Change}, publisher = {Springer}, address = {Berlin}, issn = {0165-0009}, doi = {10.1007/s10584-019-02366-0}, pages = {1 -- 16}, year = {2019}, language = {en} } @article{CampenKowalskiLyonsetal.2019, author = {Campen, R. and Kowalski, Julia and Lyons, W.B. and Tulaczyk, S. and Dachwald, Bernd and Pettit, E. and Welch, K. A. and Mikucki, J.A.}, title = {Microbial diversity of an Antarctic subglacial community and high-resolution replicate sampling inform hydrological connectivity in a polar desert}, series = {Environmental Microbiology}, journal = {Environmental Microbiology}, number = {accepted article}, publisher = {Wiley}, address = {Weinheim}, issn = {1462-2920}, doi = {10.1111/1462-2920.14607}, year = {2019}, language = {en} } @article{LyonsMikuckiGermanetal.2019, author = {Lyons, W. Berry and Mikucki, Jill A. and German, Laura A. and Welch, Kathleen A. and Welch, Susan A. and Gardener, Christopher B. and Tulaczyk, Slawek M. and Pettit, Erin C. and Kowalski, Julia and Dachwald, Bernd}, title = {The Geochemistry of Englacial Brine from Taylor Glacier, Antarctica}, series = {Journal of Geophysical Research: Biogeosciences}, journal = {Journal of Geophysical Research: Biogeosciences}, publisher = {Wiley}, address = {Hoboken}, issn = {2169-8961}, doi = {10.1029/2018JG004411}, year = {2019}, language = {en} } @incollection{FranzenSteckenPfaffetal.2019, author = {Franzen, Julian and Stecken, Jannis and Pfaff, Raphael and Kuhlenk{\"o}tter, Bernd}, title = {Using the Digital Shadow for a Prescriptive Optimization of Maintenance and Operation : The Locomotive in the Context of the Cyber-Physical System}, series = {Advances in Production, Logistics and Traffic}, booktitle = {Advances in Production, Logistics and Traffic}, publisher = {Springer}, address = {Cham}, isbn = {978-3-030-13535-5}, doi = {10.1007/978-3-030-13535-5_19}, pages = {265 -- 276}, year = {2019}, abstract = {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.}, language = {en} } @article{FunkeBeckmannAbanteriba2019, author = {Funke, Harald and Beckmann, Nils and Abanteriba, Sylvester}, title = {An overview on dry low NOx micromix combustor development for hydrogen-rich gas turbine applications}, series = {International Journal of Hydrogen Energy}, volume = {44}, journal = {International Journal of Hydrogen Energy}, number = {13}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0360-3199}, doi = {10.1016/j.ijhydene.2019.01.161}, pages = {6978 -- 6990}, year = {2019}, language = {en} } @article{BreuerPilasGuthmannetal.2019, author = {Breuer, Lars and Pilas, Johanna and Guthmann, Eric and Sch{\"o}ning, Michael Josef and Thoelen, Ronald and Wagner, Torsten}, title = {Towards light-addressable flow control: responsive hydrogels with incorporated graphene oxide as laser-driven actuator structures within microfluidic channels}, series = {Sensor and Actuators B: Chemical}, volume = {288}, journal = {Sensor and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2019.02.086}, pages = {579 -- 585}, year = {2019}, language = {en} } @article{JungMuellerStaat2019, author = {Jung, Alexander and M{\"u}ller, Wolfram and Staat, Manfred}, title = {Optimization of the flight technique in ski jumping: the influence of wind}, number = {Early view}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.jbiomech.2019.03.023}, year = {2019}, language = {en} } @inproceedings{GrundmannBauerBorchersetal.2018, author = {Grundmann, Jan Thimo and Bauer, Waldemar and Borchers, Kai and Dumont, Etienne and Grimm, Christian D. and Ho, Tra-Mi and Jahnke, Rico and Lange, Caroline and Maiwald, Volker and Mikulz, Eugen and Quantius, Dominik and Reershemius, Siebo and Renger, Thomas and Riemann, Johannes and Sasaki, Kaname and Seefeldt, Patric and Spietz, Peter and Spr{\"o}witz, Tom and Toth, Norbert and Wejmo, Elisabet and Biele, Jens and Krause, Christian and Cerotti, Matteo and Peloni, Alessandro and Dachwald, Bernd}, title = {Small Spacecraft Solar Sailing for Small Solar System Body Multiple Rendezvous and Landing}, series = {2018 IEEE Aerospace Conference : 3-10 March 2018}, booktitle = {2018 IEEE Aerospace Conference : 3-10 March 2018}, isbn = {978-1-5386-2014-4}, pages = {20 Seiten}, year = {2018}, language = {en} } @article{ScheerHendersonKapelyukhetal.2019, author = {Scheer, Nico and Henderson, Colin James and Kapelyukh, Yury and Rode, Anja and Mclaren, Aileen W. and MacLeod, Alastair Kenneth and Lin, De and Wright, Jayne and Stanley, Lesley and Wolf, C. Roland}, title = {An extensively humanised mouse model to predict pathways of drug disposition, drug/drug interactions, and to facilitate the design of clinical trials}, series = {Drug Metabolism and Disposition}, journal = {Drug Metabolism and Disposition}, number = {Early view}, doi = {10.1124/dmd.119.086397}, pages = {69 Seiten}, year = {2019}, language = {en} } @article{JanThimoBauerBieleetal.2019, author = {Jan Thimo, Grundmann and Bauer, Waldemar and Biele, Jens and Boden, Ralf and Ceriotti, Matteo and Cordero, Federico and Dachwald, Bernd and Dumont, Etienne and Grimm, Christian D. and Hercik, David}, title = {Capabilities of Gossamer-1 derived small spacecraft solar sails carrying Mascot-derived nanolanders for in-situ surveying of NEAs}, series = {Acta Astronautica}, volume = {156}, journal = {Acta Astronautica}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0094-5765}, doi = {10.1016/j.actaastro.2018.03.019}, pages = {330 -- 362}, year = {2019}, language = {en} } @inproceedings{GoettenHavermannBraunetal.2018, author = {G{\"o}tten, Falk and Havermann, Marc and Braun, Carsten and Gomez, Francisco and Bil, Cees}, title = {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}, series = {2018 Aviation Technology, Integration, and Operations Conference, AIAA AVIATION Forum}, booktitle = {2018 Aviation Technology, Integration, and Operations Conference, AIAA AVIATION Forum}, issn = {1533-385X}, doi = {10.2514/6.2018-3192}, pages = {Article 3192}, year = {2018}, language = {en} } @book{WagemannTippkoetter2019, author = {Wagemann, Kurt and Tippk{\"o}tter, Nils}, title = {Biorefineries / Kurt Wagemann, Nils Tippk{\"o}tter (editors)}, series = {Advances in biochemical engineering/biotechnology book series (ABE)}, journal = {Advances in biochemical engineering/biotechnology book series (ABE)}, publisher = {Springer}, address = {Cham (Switzerland)}, isbn = {978-3-319-97117-9}, doi = {10.1007/978-3-319-97119-3}, pages = {VI, 549 Seiten}, year = {2019}, language = {en} } @article{SalpatiChuChenetal.2014, author = {Salpati, Laurent and Chu, Xiaoyan and Chen, Liangfu and Prasad, Bhagwat and Dallas, Shannon and Evers, Raymond and Mamaril-Fishman, Donna and Geier, Ethan G. and Kehler, Jonathan and Kunta, Jeevan and Mezler, Mario and Laplanche, Loic and Pang, Jodie and Soars, Matthew G. and Unadkat, Jashvant D. and van Waterschoot, Robert A.B. and Yabut, Jocelyn and Schinkel, Alfred H. and Scheer, Nico and Rode, Anja}, title = {Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {8}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057976}, pages = {1301 -- 1313}, year = {2014}, abstract = {Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography-tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.}, language = {en} } @article{LuisierLempiaeinenScherbichleretal.2014, author = {Luisier, Rapha{\"e}lle and Lempi{\"a}inen, Harri and Scherbichler, Nina and Braeuning, Albert and Geissler, Miriam and Dubost, Valerie and M{\"u}ller, Arne and Scheer, Nico and Chibout, Salah-Dine and Hara, Hisanori and Picard, Frank and Theil, Diethilde and Couttet, Philippe and Vitobello, Antonio and Grenet, Olivier and Grasl-Kraupp, Bettina and Ellinger-Ziegelbauer, Heidrung and Thomson, John P. and Meehan, Richard R. and Elcombe, Clifford R. and Henderson, Colin J. and Wolf, C. Roland and Schwarz, Michael and Moulin, Pierre and Terranova, Remi and Moggs, Jonathan G.}, title = {Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors}, series = {Toxicological Sciences}, volume = {139}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {https://doi.org/10.1093/toxsci/kfu038}, pages = {501 -- 511}, year = {2014}, abstract = {The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.}, language = {en} } @article{HendersonMclaughlinScheeretal.2015, author = {Henderson, Colin J. and Mclaughlin, Lesley A. and Scheer, Nico and Stanley, Lesley A. and Wolf, C. Roland}, title = {Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s}, series = {Molecular Pharmacology}, volume = {87}, journal = {Molecular Pharmacology}, number = {4}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-0111}, doi = {10.1124/mol.114.097394}, pages = {733 -- 739}, year = {2015}, language = {en} } @article{HoughNalwalkDingetal.2015, author = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico}, title = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {9}, issn = {1521-009x}, doi = {10.1124/dmd.115.065490}, pages = {1326 -- 1330}, year = {2015}, language = {en} } @article{ScheerKapelyukhRodeetal.2015, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland}, title = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009x}, doi = {10.1124/dmd.115.065656}, pages = {1679 -- 1690}, year = {2015}, language = {en} }