@article{StanleyHorsburghRossetal.2006, author = {Stanley, Lesley A. and Horsburgh, Brian C. and Ross, Jillian and Scheer, Nico and Wolf, C. Roland}, title = {Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity}, series = {Drug Metabolism Reviews}, volume = {38}, journal = {Drug Metabolism Reviews}, number = {3}, issn = {1097-9883}, doi = {10.1080/03602530600786232}, pages = {515 -- 597}, year = {2006}, language = {en} } @article{StanleyHorsburghRossetal.2009, author = {Stanley, Lesley A. and Horsburgh, Brian C. and Ross, Jillian and Scheer, Nico and Wolf, C. Roland}, title = {Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior}, series = {Drug Metabolism Reviews}, volume = {41}, journal = {Drug Metabolism Reviews}, number = {1}, publisher = {Taylor \& Francis}, address = {London}, issn = {1097-9883}, doi = {10.1080/03602530802605040}, pages = {27 -- 65}, year = {2009}, language = {en} } @article{HendersonScheerWolf2009, author = {Henderson, Colin J. and Scheer, Nico and Wolf, C. Roland}, title = {Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man}, series = {Expert Review of Clinical Pharmacology}, volume = {2}, journal = {Expert Review of Clinical Pharmacology}, number = {2}, publisher = {Taylor \& Francis}, address = {London}, issn = {1751-2441}, doi = {10.1586/17512433.2.2.105}, pages = {105 -- 109}, year = {2009}, language = {en} } @article{ScheerWolf2013, author = {Scheer, Nico and Wolf, C. Roland}, title = {Xenobiotic receptor humanized mice and their utility}, series = {Drug Metabolism Reviews}, journal = {Drug Metabolism Reviews}, number = {1}, publisher = {Taylor \& Francis}, address = {London}, issn = {1097-9883}, doi = {10.3109/03602532.2012.738687}, pages = {110 -- 121}, year = {2013}, language = {en} } @article{ScheerWolf2014, author = {Scheer, Nico and Wolf, C. Roland}, title = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications}, series = {Xenobiotica}, volume = {44}, journal = {Xenobiotica}, number = {2}, publisher = {Taylor \& Francis}, address = {Abingdon}, issn = {1366-5928}, doi = {10.3109/00498254.2013.815831}, pages = {96 -- 108}, year = {2014}, abstract = {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.}, language = {en} } @article{ScheerWilson2016, author = {Scheer, Nico and Wilson, Ian D.}, title = {A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity}, series = {Drug Discovery Today}, volume = {21}, journal = {Drug Discovery Today}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2015.09.002}, pages = {250 -- 263}, year = {2016}, abstract = {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.}, language = {en} } @article{ScheerCamposOrtega1999, author = {Scheer, Nico and Campos-Ortega, Jos{\´e} A.}, title = {Use of the Gal4-UAS technique for targeted gene expression in the zebrafish}, series = {Mechanism of Development}, volume = {80}, journal = {Mechanism of Development}, number = {2}, issn = {0925-4773}, doi = {10.1016/S0925-4773(98)00209-3}, pages = {153 -- 158}, year = {1999}, language = {en} } @article{HalbachScheer2000, author = {Halbach, Thorsten and Scheer, Nico}, title = {Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins}, series = {Nucleic Acids Research}, volume = {28}, journal = {Nucleic Acids Research}, number = {18}, issn = {1362-4962}, doi = {10.1093/nar/28.18.3542}, pages = {3542 -- 3550}, year = {2000}, language = {en} } @article{ScheerGrothHansetal.2001, author = {Scheer, Nico and Groth, Anne and Hans, Stefan and Campos-Ortega, Jos{\´e} A.}, title = {An instructive function for Notch in promoting gliogenesis in the zebrafish retina}, series = {Development}, volume = {128}, journal = {Development}, number = {7}, issn = {0950-1991}, pages = {1099 -- 1107}, year = {2001}, language = {en} } @article{LawsonScheerPhametal.2001, author = {Lawson, Nathan D. and Scheer, Nico and Pham, Van N. and Kim, Ceol-Hee and Chitnis, Ajay B. and Campos-Ortega, Jos{\´e} A. and Weinstein, Brant M.}, title = {Notch signaling is required for arterial-venous differentiation during embryonic vascular development}, series = {Development}, volume = {128}, journal = {Development}, number = {19}, issn = {1477-9129}, pages = {3675 -- 3683}, year = {2001}, language = {en} } @article{ScheerRiedlWarrenetal.2002, author = {Scheer, Nico and Riedl, Iris and Warren, J.T. and Kuwada, John Y. and Campos-Ortega, Jos{\´e} A.}, title = {A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish}, series = {Mechanism of Development}, volume = {112}, journal = {Mechanism of Development}, number = {1-2}, issn = {0925-4773}, doi = {10.1016/S0925-4773(01)00621-9}, pages = {9 -- 14}, year = {2002}, language = {en} } @article{HansScheerRiedletal.2004, author = {Hans, Stefan and Scheer, Nico and Riedl, Iris and Weiz{\"a}cker, Elisabeth von and Blader, Patrick and Campos-Ortega, Jos{\´e} A.}, title = {her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling}, series = {Development}, volume = {131}, journal = {Development}, number = {12}, issn = {1477-9129}, doi = {10.1242/dev.01167}, pages = {2957 -- 2969}, year = {2004}, language = {en} } @article{ReugelsBoggettiScheeretal.2006, author = {Reugels, Alexander M. and Boggetti, Barbara and Scheer, Nico and Campos-Ortega, Jos{\´e} A.}, title = {Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio}, series = {Developmental Dynamics}, volume = {235}, journal = {Developmental Dynamics}, number = {4}, issn = {1097-0177}, doi = {10.1002/dvdy.20699}, pages = {934 -- 948}, year = {2006}, language = {en} } @article{ScheerKapelyukhMcEwanetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and McEwan, Jillian and Beuger, Vincent and Stanley, Lesley A. and Rode, Anja and Wolf, C. Roland}, title = {Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines}, series = {Molecular Pharmacology}, volume = {81}, journal = {Molecular Pharmacology}, number = {1}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.075192}, pages = {63 -- 72}, year = {2012}, abstract = {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.}, language = {en} } @article{ScheerRossRodeetal.2008, author = {Scheer, Nico and Ross, Jillian and Rode, Anja and Zevnik, Branko and Niehaves, Sandra and Faust, Nicole and Wolf, C. Roland}, title = {A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response}, series = {Journal of Clinical Investigation}, volume = {118}, journal = {Journal of Clinical Investigation}, number = {9}, issn = {1558-8238}, doi = {https://doi.org/10.1172/JCI35483}, pages = {3228 -- 3239}, year = {2008}, language = {en} } @article{ScheerRossKapelyukhetal.2010, author = {Scheer, Nico and Ross, Jillian and Kapelyukh, Yury and Rode, Anja and Wolf, C. Roland}, title = {In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice}, series = {Drug Metabolism and Disposition}, volume = {38}, journal = {Drug Metabolism and Disposition}, number = {7}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009X}, doi = {10.1124/dmd.109.031872}, pages = {1046 -- 1053}, year = {2010}, abstract = {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.}, language = {en} } @article{RossPlummerRodeetal.2010, author = {Ross, Jillian and Plummer, Simon M. and Rode, Anja and Scheer, Nico and Bower, Conrad C. and Vogel, Ortwin and Henderson, Colin J. and Wolf, C. Roland and Elcombe, Clifford R.}, title = {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}, series = {Toxicological Sciences}, volume = {116}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1096-0929}, doi = {10.1093/toxsci/kfq118}, pages = {452 -- 466}, year = {2010}, abstract = {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.}, language = {en} } @article{ScheerKapelyukhRodeetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland}, title = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines}, series = {Molecular Pharmacology}, volume = {82}, journal = {Molecular Pharmacology}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.112.080036}, pages = {1022 -- 1029}, year = {2012}, abstract = {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.}, language = {en} } @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} } @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} } @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} } @article{KlubertMalechaSparla2018, author = {Klubert, Joachim and Malecha, Hartmut and Sparla, Peter}, title = {Modernisierung der geod{\"a}tischen Messtechnik der Urfttalsperre}, series = {Wasserwirtschaft}, volume = {108}, journal = {Wasserwirtschaft}, number = {10}, publisher = {Springer Vieweg}, address = {Wiesbaden}, issn = {0043-0978}, pages = {14 -- 18}, year = {2018}, language = {de} } @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} } @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} } @article{DallasSalphatiGomezZepedaetal.2016, author = {Dallas, Shannon and Salphati, Laurent and Gomez-Zepeda, David and Wanek, Thomas and Chen, Liangfu and Chu, Xiaoyan and Kunta, Jeevan and Mezler, Mario and Menet, Marie-Claude and Chasseigneaux, Stephanie and Decl{\`e}ves, Xavier and Langer, Oliver and Pierre, Esaie and DiLoreto, Karen and Hoft, Carolin and Laplanche, Loic and Pang, Jodie and Pereira, Tony and Andonian, Clara and Simic, Damir and Rode, Anja and Yabut, Jocelyn and Zhang, Xiaolin and Scheer, Nico}, title = {Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model}, series = {Molecular Pharmacology}, volume = {89}, journal = {Molecular Pharmacology}, number = {5}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.115.102079}, pages = {492 -- 504}, year = {2016}, abstract = {Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp-/-) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP.}, language = {en} } @article{ZhangHeimbachScheeretal.2016, author = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan}, title = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling}, series = {Journal of Pharmaceutical Sciences}, volume = {Volume 105}, journal = {Journal of Pharmaceutical Sciences}, number = {Issue 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-3549}, doi = {doi.org/10.1016/j.xphs.2016.01.021}, pages = {1398 -- 1404}, year = {2016}, abstract = {NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.}, language = {en} } @article{WilsonWilsonScheeretal.2017, author = {Wilson, Ian D. and Wilson, Claire E. and Scheer, Nico and Dickie, A.P. and Schreiter, K. and Wilson, E. M. and Riley, R. J. and Wehr, R. and Bial, J.}, title = {The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice}, series = {Biochemical pharmacology}, volume = {Volume 135}, journal = {Biochemical pharmacology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2968}, doi = {10.1016/j.bcp.2017.03.015}, pages = {139 -- 150}, year = {2017}, language = {en} } @article{LeschingerBirgelHackletal.2019, author = {Leschinger, Tim and Birgel, Stefan and Hackl, Michael and Staat, Manfred and M{\"u}ller, Lars Peter and Wegmann, Kilian}, title = {A musculoskeletal shoulder simulation of moment arms and joint reaction forces after medialization of the supraspinatus footprint in rotator cuff repair}, series = {Computer Methods in Biomechanics and Biomedical Engineering}, journal = {Computer Methods in Biomechanics and Biomedical Engineering}, number = {Early view}, publisher = {Taylor \& Francis}, address = {London}, doi = {10.1080/10255842.2019.1572749}, year = {2019}, language = {en} } @article{WilsonDickieSchreiteretal.2018, author = {Wilson, C. E. and Dickie, A. P. and Schreiter, K. and Wehr, R. and Wilson, E. M. and Bial, J. and Scheer, Nico and Wilson, I. D. and Riley, R. J.}, title = {The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice}, series = {Archives of Toxicology}, volume = {92}, journal = {Archives of Toxicology}, number = {6}, publisher = {Springer}, issn = {1432-0738}, doi = {10.1007/s00204-018-2212-1}, pages = {1953 -- 1967}, year = {2018}, abstract = {The pharmacokinetics of diclofenac were investigated following single oral doses of 10 mg/kg to chimeric liver humanized and murinized FRG and C57BL/6 mice. In addition, the metabolism and excretion were investigated in chimeric liver humanized and murinized FRG mice. Diclofenac reached maximum blood concentrations of 2.43 ± 0.9 µg/mL (n = 3) at 0.25 h post-dose with an AUCinf of 3.67 µg h/mL and an effective half-life of 0.86 h (n = 2). In the murinized animals, maximum blood concentrations were determined as 3.86 ± 2.31 µg/mL at 0.25 h post-dose with an AUCinf of 4.94 ± 2.93 µg h/mL and a half-life of 0.52 ± 0.03 h (n = 3). In C57BL/6J mice, mean peak blood concentrations of 2.31 ± 0.53 µg/mL were seen 0.25 h post-dose with a mean AUCinf of 2.10 ± 0.49 µg h/mL and a half-life of 0.51 ± 0.49 h (n = 3). Analysis of blood indicated only trace quantities of drug-related material in chimeric humanized and murinized FRG mice. Metabolic profiling of urine, bile and faecal extracts revealed a complex pattern of metabolites for both humanized and murinized animals with, in addition to unchanged parent drug, a variety of hydroxylated and conjugated metabolites detected. The profiles in humanized mice were different to those of both murinized and wild-type animals, e.g., a higher proportion of the dose was detected in the form of acyl glucuronide metabolites and much reduced amounts as taurine conjugates. Comparison of the metabolic profiles obtained from the present study with previously published data from C57BL/6J mice and humans revealed a greater, though not complete, match between chimeric humanized mice and humans, such that the liver humanized FRG model may represent a model for assessing the biotransformation of such compounds in humans.}, language = {en} } @article{HueningHillgaertnerReke2019, author = {H{\"u}ning, Felix and Hillg{\"a}rtner, Michael and Reke, Michael}, title = {Rolling Labs - Teaching Vehicle Electronics from the Beginning}, series = {International Journal of Engineering Pedagogy (iJEP)}, volume = {9}, journal = {International Journal of Engineering Pedagogy (iJEP)}, number = {1}, issn = {2192-4880}, doi = {10.3991/ijep.v9i1.9241}, pages = {34 -- 49}, year = {2019}, language = {en} } @article{RauppSchmittWalzetal.2018, author = {Raupp, Sebastian M. and Schmitt, Marcel and Walz, Anna-Lena and Diehm, Ralf and Hummel, Helga and Scharfer, Philip and Schabel, Wilhelm}, title = {Slot die stripe coating of low viscous fluids}, series = {Journal of Coatings Technology and Research}, volume = {15}, journal = {Journal of Coatings Technology and Research}, number = {5}, publisher = {Springer}, issn = {1935-3804}, doi = {10.1007/s11998-017-0039-y}, pages = {899 -- 911}, year = {2018}, abstract = {Slot die coating is applied to deposit thin and homogenous films in roll-to-roll and sheet-to-sheet applications. The critical step in operation is to choose suitable process parameters within the process window. In this work, we investigate an upper limit for stripe coatings. This maximum film thickness is characterized by stripe merging which needs to be avoided in a stable process. It is shown that the upper limit reduces the process window for stripe coatings to a major extent. As a result, stripe coatings at large coating gaps and low viscosities are only possible for relatively thick films. Explaining the upper limit, a theory of balancing the side pressure in the gap region in the cross-web direction has been developed.}, language = {en} } @article{ZieburaBremenSchleifenbaumetal.2018, author = {Ziebura, Dawid and Bremen, Sebastian and Schleifenbaum, Johannes Henrich and Gebhardt, Andreas}, title = {Machbarkeitsstudie zur Verarbeitung von nicht rostendem Stahl 1.4404 unter Verwendung einer Diodenlaser-basierten LPBF-Maschine mit kartesischem Achssystem}, series = {RTejournal - Forum f{\"u}r Rapid Technologie}, volume = {15}, journal = {RTejournal - Forum f{\"u}r Rapid Technologie}, issn = {1614-0923}, year = {2018}, language = {de} } @article{DotzauerPfeifferLaueretal.2019, author = {Dotzauer, Martin and Pfeiffer, Diana and Lauer, Markus and Pohl, Marcel and Mauky, Eric and B{\"a}r, Katharina and Sonnleitner, Matthias and Z{\"o}rner, Wilfried and Hudde, Jessica and Schwarz, Bj{\"o}rn and Faßauer, Burkhardt and Dahmen, Markus and Rieke, Christian and Herbert, Johannes and Thr{\"a}n, Daniela}, title = {How to measure flexibility - Performance indicators for demand driven power generation from biogas plants}, series = {Renewable Energy}, journal = {Renewable Energy}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0960-1481}, doi = {10.1016/j.renene.2018.10.021}, pages = {135 -- 146}, year = {2019}, language = {en} } @article{KotliarLanzl2018, author = {Kotliar, Konstantin and Lanzl, Ines}, title = {Vaskul{\"a}re Biomarker der retinalen Gef{\"a}βanalyse}, series = {Klinische Monatsbl{\"a}tter fur Augenheilkunde}, volume = {235}, journal = {Klinische Monatsbl{\"a}tter fur Augenheilkunde}, number = {12}, publisher = {Thieme}, address = {Stuttgart}, issn = {0023-2165}, doi = {10.1055/a-0774-7987}, pages = {1352 -- 1359}, year = {2018}, abstract = {Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gef{\"a}ßver{\"a}nderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gef{\"a}ße beeinflussen im pr{\"a}-, post- und kapillaren Bereich den Blutfluss und str{\"o}mungsbedingte Stoffwechselverh{\"a}ltnisse passiv und aktiv {\"u}ber den Gef{\"a}ßdurchmesser. Retinale Gef{\"a}ße gleichen von Aufbau und Funktion den zerebralen Gef{\"a}ßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gef{\"a}ßweiten berechneten Biomarkern soll eine Aussage {\"u}ber die Prognose von systemischen vaskul{\"a}r bedingten Erkrankungen getroffen werden. Die statische retinale Gef{\"a}ßanalyse befasst sich mit der Untersuchung des Zustandes der pr{\"a}- und postkapillaren Gef{\"a}ßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gef{\"a}ßanalyse wird der L{\"a}ngsschnitt eines retinalen Gef{\"a}ßes nicht invasiv funktionell und strukturell {\"u}ber einen Zeitraum vor, w{\"a}hrend und nach einer spezifischen vaskul{\"a}ren Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ans{\"a}tzen. Mittels retinaler Gef{\"a}ßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gyn{\"a}kologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgef{\"u}hrt. Mit der statischen retinalen Gef{\"a}ßanalyse steht eine kosteng{\"u}nstige, reproduzierbare, nicht invasive Screeningtechnik zur Verf{\"u}gung, um eine prognostische Aussage {\"u}ber die Gef{\"a}ßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gef{\"a}ßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gef{\"a}ße zeitkontinuierlich untersucht. Die Evaluation vaskul{\"a}rer Erkrankungen sowie zerebro- bzw. kardiovaskul{\"a}rer Morbidit{\"a}t und Mortalit{\"a}t mittels mehrerer methodologischer Modalit{\"a}ten retinaler Gef{\"a}ßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftstr{\"a}chtige diagnostische Perspektive. Die interdisziplin{\"a}re klinische Anwendung dieser vaskul{\"a}ren Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten.}, language = {de} } @article{BleilevensHillGrzannaetal.2019, author = {Bleilevens, Christian and Hill, Aileen and Grzanna, Tim and Fechter, Tamara and Bohnen, Melanie and Weber, Hans-Joachim and Beckers, Christian and Borosch, Sebastian and Zayat, Rashad and Benstoem, Carin and Rossaint, Rolf and Goetzenich, Andreas}, title = {In vitro head-to-head comparison of anticoagulation properties of two heparin brands in a human blood miniature mock loop}, series = {Interactive cardiovascular and thoracic surgery}, volume = {28}, journal = {Interactive cardiovascular and thoracic surgery}, number = {1}, issn = {1569-9285}, doi = {10.1093/icvts/ivy206}, pages = {120 -- 127}, year = {2019}, language = {en} } @article{HeinkeKnickerAlbracht2018, author = {Heinke, Lars N. and Knicker, Axel J. and Albracht, Kirsten}, title = {Evaluation of passively induced shoulder stretch reflex using an isokinetic dynamometer in male overhead athletes}, series = {Isokinetics and Exercise Science}, volume = {26}, journal = {Isokinetics and Exercise Science}, number = {4}, publisher = {IOS Press}, address = {Amsterdam}, issn = {1878-5913}, doi = {10.3233/IES-184111}, pages = {265 -- 274}, year = {2018}, abstract = {BACKGROUND: Muscle stretch reflexes are widely considered to beneficially influence joint stability and power generation in the lower limbs. While in the upper limbs and especially in the muscles surrounding the shoulder joint such evidence is lacking. OBJECTIVE: To quantify the electromyographical response in the muscles crossing the shoulder of specifically trained overhead athletes to an anterior perturbation force. METHODS: Twenty healthy male participants performed six sets of different external shoulder rotation stretches on an isokinetic dynamometer over a range of amplitudes and muscle pre-activation moment levels. All stretches were applied with a dynamometer acceleration of 10,000∘/s2 and a velocity of 150∘/s. Electromyographical response was measured via sEMG. RESULTS: Consistent reflexes were not observed in all experimental conditions. The reflex latencies revealed a significant muscle main effect (F (2,228) = 99.31, p< 0.001; η2= 0.466; f= 0.934) and a pre-activation main effect (F (1,228) = 142.21, p< 0.001; η2= 0.384; f= 1.418). The stretch reflex amplitude yielded a significant pre-activation main effect (F (1,222) = 470.373, p< 0.001; η2= 0.679; f= 1.454). CONCLUSION: Short latency muscle reflexes showed a tendency to an anterior to posterior muscle recruitment whereby the main internal rotator muscles of the shoulder revealed the most consistent results.}, language = {en} } @article{VitiValeroGualtieri2019, author = {Viti, Nicolo and Valero, Daniel and Gualtieri, Carlo}, title = {Numerical Simulation of Hydraulic Jumps. Part 2: Recent Results and Future Outlook}, series = {Water}, volume = {11}, journal = {Water}, number = {1}, issn = {2073-4441}, doi = {10.3390/w11010028}, pages = {Art. Nr. 28}, year = {2019}, language = {en} } @article{ValeroVitiGualtieri2019, author = {Valero, Daniel and Viti, Nicolo and Gualtieri, Carlo}, title = {Numerical Simulation of Hydraulic Jumps. Part 1: Experimental Data for Modelling Performance Assessment}, series = {Water}, volume = {11}, journal = {Water}, number = {1}, publisher = {MDPI}, address = {Basel}, issn = {2073-4441}, doi = {10.3390/w11010036}, pages = {Art. Nr. 36}, year = {2019}, language = {en} } @article{LauraDrechslerErdtetal.2018, author = {Laura, C.O. and Drechsler, Klaus and Erdt, M. and Wesarg, S. and Bale, R.}, title = {Intervention assessment tool for primary tumors in the liver}, series = {Current Directions in Biomedical Engineering}, volume = {4}, journal = {Current Directions in Biomedical Engineering}, number = {1}, publisher = {De Gruyter}, address = {Berlin}, issn = {2364-5504}, doi = {10.1515/cdbme-2018-0081}, pages = {337 -- 340}, year = {2018}, abstract = {After a liver tumor intervention the medical doctor has to compare both pre and postoperative CT acquisitions to ensure that all carcinogenic cells are destroyed. A correct assessment of the intervention is of vital importance, since it will reduce the probability of tumor recurrence. Some methods have been proposed to support the medical doctors during the assessment process, however, all of them focus on secondary tumors. In this paper a tool is presented that enables the outcome validation for both primary and secondary tumors. Therefore, a multiphase registration (preoperative arterial and portal phases) followed by a registration between the pre and postoperative CT images is carried out. The first registration is in charge of the primary tumors that are only visible in the arterial phase. The secondary tumors will be incorporated in the second registration step. Finally, the part of the tumor that was not covered by the necrosis is quantified and visualized. The method has been tested in 9 patients, with an average registration error of 1.41 mm.}, language = {en} } @article{BronderPoghossianJessingetal.2019, author = {Bronder, Thomas and Poghossian, Arshak and Jessing, Max P. and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Surface regeneration and reusability of label-free DNA biosensors based on weak polyelectrolyte-modified capacitive field-effect structures}, series = {Biosensors and Bioelectronics}, volume = {126}, journal = {Biosensors and Bioelectronics}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0956-5663}, doi = {10.1016/j.bios.2018.11.019}, pages = {510 -- 517}, year = {2019}, language = {en} }