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 - 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 - 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 - JOUR A1 - Klubert, Joachim A1 - Malecha, Hartmut A1 - Sparla, Peter T1 - Modernisierung der geodätischen Messtechnik der Urfttalsperre JF - Wasserwirtschaft T2 - Modernisation of the geodetic measurement technology of the Urft dam Y1 - 2018 SN - 0043-0978 N1 - gedruckt in der Bereichsbibliothek Bayernallee vorhanden VL - 108 IS - 10 SP - 14 EP - 18 PB - Springer Vieweg CY - Wiesbaden 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 - JOUR A1 - Salpati, Laurent A1 - Chu, Xiaoyan A1 - Chen, Liangfu A1 - Prasad, Bhagwat A1 - Dallas, Shannon A1 - Evers, Raymond A1 - Mamaril-Fishman, Donna A1 - Geier, Ethan G. A1 - Kehler, Jonathan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Soars, Matthew G. A1 - Unadkat, Jashvant D. A1 - van Waterschoot, Robert A.B. A1 - Yabut, Jocelyn A1 - Schinkel, Alfred H. A1 - Scheer, Nico A1 - Rode, Anja T1 - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins JF - Drug Metabolism and Disposition N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Henderson, Colin J. A1 - Mclaughlin, Lesley A. A1 - Scheer, Nico A1 - Stanley, Lesley A. A1 - Wolf, C. Roland T1 - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s JF - Molecular Pharmacology Y1 - 2015 U6 - http://dx.doi.org/10.1124/mol.114.097394 SN - 1521-0111 VL - 87 IS - 4 SP - 733 EP - 739 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Hough, Lindsay B. A1 - Nalwalk, Julia W. A1 - Ding, Xinxin A1 - Scheer, Nico T1 - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065490 SN - 1521-009x VL - 43 IS - 9 SP - 1326 EP - 1330 ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Oswald, Stefan A1 - Busch, Diana A1 - Mclaughlin, Lesley A. A1 - Lin, De A1 - Henderson, Colin J. A1 - Wolf, C. Roland T1 - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065656 SN - 1521-009x VL - 43 IS - 11 SP - 1679 EP - 1690 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Dallas, Shannon A1 - Salphati, Laurent A1 - Gomez-Zepeda, David A1 - Wanek, Thomas A1 - Chen, Liangfu A1 - Chu, Xiaoyan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Menet, Marie-Claude A1 - Chasseigneaux, Stephanie A1 - Declèves, Xavier A1 - Langer, Oliver A1 - Pierre, Esaie A1 - DiLoreto, Karen A1 - Hoft, Carolin A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Pereira, Tony A1 - Andonian, Clara A1 - Simic, Damir A1 - Rode, Anja A1 - Yabut, Jocelyn A1 - Zhang, Xiaolin A1 - Scheer, Nico T1 - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model JF - Molecular Pharmacology N2 - 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. Y1 - 2016 U6 - http://dx.doi.org/10.1124/mol.115.102079 SN - 1521-0111 VL - 89 IS - 5 SP - 492 EP - 504 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Zhang, Jin A1 - Heimbach, Tycho A1 - Scheer, Nico A1 - Barve, Avantika A1 - Li, Wenkui A1 - Lin, Wen A1 - He, Handan T1 - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling JF - Journal of Pharmaceutical Sciences N2 - 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. Y1 - 2016 U6 - http://dx.doi.org/doi.org/10.1016/j.xphs.2016.01.021 SN - 0022-3549 VL - Volume 105 IS - Issue 4 SP - 1398 EP - 1404 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wilson, Ian D. A1 - Wilson, Claire E. A1 - Scheer, Nico A1 - Dickie, A.P. A1 - Schreiter, K. A1 - Wilson, E. M. A1 - Riley, R. J. A1 - Wehr, R. A1 - Bial, J. T1 - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice JF - Biochemical pharmacology Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.bcp.2017.03.015 SN - 1873-2968 VL - Volume 135 SP - 139 EP - 150 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Leschinger, Tim A1 - Birgel, Stefan A1 - Hackl, Michael A1 - Staat, Manfred A1 - Müller, Lars Peter A1 - Wegmann, Kilian T1 - A musculoskeletal shoulder simulation of moment arms and joint reaction forces after medialization of the supraspinatus footprint in rotator cuff repair JF - Computer Methods in Biomechanics and Biomedical Engineering Y1 - 2019 U6 - http://dx.doi.org/10.1080/10255842.2019.1572749 IS - Early view PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Wilson, C. E. A1 - Dickie, A. P. A1 - Schreiter, K. A1 - Wehr, R. A1 - Wilson, E. M. A1 - Bial, J. A1 - Scheer, Nico A1 - Wilson, I. D. A1 - Riley, R. J. T1 - The pharmacokinetics and metabolism of diclofenac in chimeric humanized and murinized FRG mice JF - Archives of Toxicology N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.1007/s00204-018-2212-1 SN - 1432-0738 VL - 92 IS - 6 SP - 1953 EP - 1967 PB - Springer ER - TY - JOUR A1 - Hüning, Felix A1 - Hillgärtner, Michael A1 - Reke, Michael T1 - Rolling Labs – Teaching Vehicle Electronics from the Beginning JF - International Journal of Engineering Pedagogy (iJEP) Y1 - 2019 U6 - http://dx.doi.org/10.3991/ijep.v9i1.9241 SN - 2192-4880 VL - 9 IS - 1 SP - 34 EP - 49 ER - TY - JOUR A1 - Raupp, Sebastian M. A1 - Schmitt, Marcel A1 - Walz, Anna-Lena A1 - Diehm, Ralf A1 - Hummel, Helga A1 - Scharfer, Philip A1 - Schabel, Wilhelm T1 - Slot die stripe coating of low viscous fluids JF - Journal of Coatings Technology and Research N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.1007/s11998-017-0039-y SN - 1935-3804 VL - 15 IS - 5 SP - 899 EP - 911 PB - Springer ER - TY - JOUR A1 - Ziebura, Dawid A1 - Bremen, Sebastian A1 - Schleifenbaum, Johannes Henrich A1 - Gebhardt, Andreas T1 - Machbarkeitsstudie zur Verarbeitung von nicht rostendem Stahl 1.4404 unter Verwendung einer Diodenlaser-basierten LPBF-Maschine mit kartesischem Achssystem JF - RTejournal - Forum für Rapid Technologie Y1 - 2018 SN - 1614-0923 VL - 15 ER - TY - JOUR A1 - Dotzauer, Martin A1 - Pfeiffer, Diana A1 - Lauer, Markus A1 - Pohl, Marcel A1 - Mauky, Eric A1 - Bär, Katharina A1 - Sonnleitner, Matthias A1 - Zörner, Wilfried A1 - Hudde, Jessica A1 - Schwarz, Björn A1 - Faßauer, Burkhardt A1 - Dahmen, Markus A1 - Rieke, Christian A1 - Herbert, Johannes A1 - Thrän, Daniela T1 - How to measure flexibility – Performance indicators for demand driven power generation from biogas plants JF - Renewable Energy Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.renene.2018.10.021 SN - 0960-1481 SP - 135 EP - 146 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kotliar, Konstantin A1 - Lanzl, Ines T1 - Vaskuläre Biomarker der retinalen Gefäβanalyse T1 - Vascular Biomarkers in Retinal Vessel Analysis JF - Klinische Monatsblätter fur Augenheilkunde N2 - Mit modernen nicht invasiven bildgebenden Verfahren lassen sich anhand der Fundusfotografie bzw. der optischen Verfilmung Aspekte der funktionellen und strukturellen retinalen Gefäßveränderungen objektiv untersuchen. Der Zustand und das Verhalten retinaler Gefäße beeinflussen im prä-, post- und kapillaren Bereich den Blutfluss und strömungsbedingte Stoffwechselverhältnisse passiv und aktiv über den Gefäßdurchmesser. Retinale Gefäße gleichen von Aufbau und Funktion den zerebralen Gefäßen und spiegeln den Zustand der Mikrozirkulation wider. Mithilfe von aus den Gefäßweiten berechneten Biomarkern soll eine Aussage über die Prognose von systemischen vaskulär bedingten Erkrankungen getroffen werden. Die statische retinale Gefäßanalyse befasst sich mit der Untersuchung des Zustandes der prä- und postkapillaren Gefäßdurchmesser der retinalen Mikrozirkulation anhand einer optischen Fundusaufnahme. Bei der dynamischen retinalen Gefäßanalyse wird der Längsschnitt eines retinalen Gefäßes nicht invasiv funktionell und strukturell über einen Zeitraum vor, während und nach einer spezifischen vaskulären Stimulation untersucht. Die genaue Methodologie der Auswertung und die Bezeichnung der Parameter variieren bei unterschiedlichen Ansätzen. Mittels retinaler Gefäßanalyse wurden bislang mehrere klinische Querschnitts- und Interventionsstudien in der Augenheilkunde und anderen Fachgebieten, inkl. Kardiologie, Neurologie, Neurochirurgie, Nephrologie, Gynäkologie, Sportmedizin, Diabetologie, Hypertensiologie usw. durchgeführt. Mit der statischen retinalen Gefäßanalyse steht eine kostengünstige, reproduzierbare, nicht invasive Screeningtechnik zur Verfügung, um eine prognostische Aussage über die Gefäßgesundheit eines individuellen Patienten zu treffen. Die dynamische retinale Gefäßanalyse besitzt ein weiteres diagnostisches Anwendungsspektrum als die statische, da sie das Verhalten retinaler Gefäße zeitkontinuierlich untersucht. Die Evaluation vaskulärer Erkrankungen sowie zerebro- bzw. kardiovaskulärer Morbidität und Mortalität mittels mehrerer methodologischer Modalitäten retinaler Gefäßanalyse mit ihren jeweiligen quantitativen Biomarkern bietet eine zukunftsträchtige diagnostische Perspektive. Die interdisziplinäre klinische Anwendung dieser vaskulären Biomarker gewinnt zunehmend an Bedeutung, sowohl in der Augenheilkunde als auch in anderen Fachgebieten. Y1 - 2018 U6 - http://dx.doi.org/10.1055/a-0774-7987 SN - 0023-2165 VL - 235 IS - 12 SP - 1352 EP - 1359 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - Bleilevens, Christian A1 - Hill, Aileen A1 - Grzanna, Tim A1 - Fechter, Tamara A1 - Bohnen, Melanie A1 - Weber, Hans-Joachim A1 - Beckers, Christian A1 - Borosch, Sebastian A1 - Zayat, Rashad A1 - Benstoem, Carin A1 - Rossaint, Rolf A1 - Goetzenich, Andreas T1 - In vitro head-to-head comparison of anticoagulation properties of two heparin brands in a human blood miniature mock loop JF - Interactive cardiovascular and thoracic surgery Y1 - 2019 U6 - http://dx.doi.org/10.1093/icvts/ivy206 SN - 1569-9285 VL - 28 IS - 1 SP - 120 EP - 127 ER - TY - JOUR A1 - Heinke, Lars N. A1 - Knicker, Axel J. A1 - Albracht, Kirsten T1 - Evaluation of passively induced shoulder stretch reflex using an isokinetic dynamometer in male overhead athletes JF - Isokinetics and Exercise Science N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.3233/IES-184111 SN - 1878-5913 VL - 26 IS - 4 SP - 265 EP - 274 PB - IOS Press CY - Amsterdam ER - TY - JOUR A1 - Viti, Nicolo A1 - Valero, Daniel A1 - Gualtieri, Carlo T1 - Numerical Simulation of Hydraulic Jumps. Part 2: Recent Results and Future Outlook JF - Water Y1 - 2019 U6 - http://dx.doi.org/10.3390/w11010028 SN - 2073-4441 VL - 11 IS - 1 SP - Art. Nr. 28 ER - TY - JOUR A1 - Valero, Daniel A1 - Viti, Nicolo A1 - Gualtieri, Carlo T1 - Numerical Simulation of Hydraulic Jumps. Part 1: Experimental Data for Modelling Performance Assessment JF - Water Y1 - 2019 U6 - http://dx.doi.org/10.3390/w11010036 SN - 2073-4441 VL - 11 IS - 1 SP - Art. Nr. 36 PB - MDPI CY - Basel ER - TY - JOUR A1 - Laura, C.O. A1 - Drechsler, Klaus A1 - Erdt, M. A1 - Wesarg, S. A1 - Bale, R. T1 - Intervention assessment tool for primary tumors in the liver JF - Current Directions in Biomedical Engineering N2 - 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. Y1 - 2018 U6 - http://dx.doi.org/10.1515/cdbme-2018-0081 SN - 2364-5504 VL - 4 IS - 1 SP - 337 EP - 340 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Bronder, Thomas A1 - Poghossian, Arshak A1 - Jessing, Max P. A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Surface regeneration and reusability of label-free DNA biosensors based on weak polyelectrolyte-modified capacitive field-effect structures JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2018.11.019 SN - 0956-5663 VL - 126 SP - 510 EP - 517 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Funke, Harald A1 - Beckmann, Nils A1 - Keinz, Jan A1 - Abanteriba, Sylvester T1 - Numerical and Experimental Evaluation of a Dual-Fuel Dry-Low-NOx Micromix Combustor for Industrial Gas Turbine Applications JF - Journal of Thermal Science and Engineering Applications Y1 - 2019 U6 - http://dx.doi.org/10.1115/1.4041495 SN - 19485085 N1 - Paper No: GT2017-64795 VL - 11 IS - 1 SP - 011015 PB - ASME CY - New York ER - TY - JOUR A1 - Arreola, Julio A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Toward an immobilization method for spore-based biosensors in oxidative environment JF - Electrochimica Acta Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.electacta.2019.01.148 VL - 302 SP - 394 EP - 401 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Buck, Raphael A1 - Läubli, Daniel A1 - Meyer, Laura A1 - Moosdorf, Andreas T1 - Re-FRESH! Mit dem Frischesortiment punkten JF - Akzente Y1 - 2013 IS - 3 SP - 36 EP - 43 ER - TY - JOUR A1 - Jung, Alexander A1 - Staat, Manfred T1 - Modeling and simulation of human induced pluripotent stem cell-derived cardiac tissue JF - GAMM - Mitteilungen der Gesellschaft für Angewandte Mathematik und Mechanik Y1 - 2019 U6 - http://dx.doi.org/10.1002/gamm.201900002 SN - 1522-2608 VL - 42 IS - 4 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Moosdorf, Andreas T1 - It’s not just the Talent, it’s the Knowledge Transfer Method JF - GC Ticker Y1 - 2009 IS - 1 SP - 16 EP - 16 ER - TY - JOUR A1 - Görgens, Stefan A1 - Greubel, Steffen A1 - Moosdorf, Andreas T1 - How to mobilize 20,000 people: Perspectives on retail and consumer goods Y1 - 2013 SP - 52 EP - 58 ER - TY - JOUR A1 - Bernecker, Andreas T1 - A European Private Company: Is Europe’s single legal form for SMEs close to approval? JF - Research Briefing N2 - This Research Briefing, issued in July 2010, concluded that: - Small and medium-sized enterprises (SMEs) in Europe have long called for a matching legal form valid across the EU (similar to that of the European company (SE) for large firms) - The main benefits would be the availability of uniform Europe-wide company structures, significant cost reductions for businesses and further integration of the internal market - Given the differing national views regarding the concrete features of the new legal form there is currently no sign of an agreement being reached at the European level in the short term; however, it is possible that progress will be made in negotiations during the year - The key issues being discussed in depth are company formation, transnationality and employee participation rights in the new European private company (SPE). Y1 - 2010 SN - 2193-5955 PB - Deutsche Bank Research CY - Frankfurt a. M. ER - TY - JOUR A1 - Thomas, Axel T1 - Zielerreichungen der Technologie- und Gründerzentren aus Sicht der kommunalen Finanzwirtschaft – dargestellt am Beispiel der Aachener Region JF - Der Gemeindehaushalt Y1 - 2018 SN - 0340-3645 VL - 119 IS - 7 SP - 149 EP - 155 PB - Kohlhammer CY - Stuttgart ER - TY - JOUR A1 - Thomas, Axel T1 - Technologiezentren in der Aachener Region – Retrospektiven und Perspektiven JF - VM Verwaltung und Management Y1 - 2018 U6 - http://dx.doi.org/10.5771/0947-9856-2018-3-147 SN - 0947-9856 VL - 24 IS - 3 SP - 147 EP - 156 PB - Nomos CY - Baden-Baden ER - TY - JOUR A1 - Schmidt, Bernd A1 - Enning, Manfred A1 - Pfaff, Raphael T1 - Güterwagen 4.0 – Der Güterwagen für das Internet der Dinge Teil 3: Einführungsszenarien für aktive, kommunikative Güterwagen JF - ETR - Eisenbahntechnische Rundschau N2 - Wenn durch innovative, automatisierte Güterwagen betriebswirtschaftliche Vorteile nutzbar gemacht werden sollen, muss die Migration auf das neue System in sinnvollen Teilschritten unter Berücksichtigung der organisationellen und betrieblichen Vereinbarkeit vorgenommen werden. Eine stufenweise Migration mit Nachrüstbarkeit und Kompatibilität kann die optimale Ausstattungsvariante für die unterschiedlichen Betriebsszenarien sowie eine Steigerung der Wirtschaftlichkeit des Gesamtsystems bieten. Y1 - 2018 SN - 0013-2845 VL - 67 IS - 5 SP - 60 EP - 64 PB - DVV Media Group CY - Hamburg ER - TY - JOUR A1 - Franzen, Julius A1 - Pinders, Erik A1 - Pfaff, Raphael A1 - Enning, Manfred T1 - RailCrowd’s virtual fleets: Make most of your asset data JF - Deine Bahn N2 - For smaller railway operators or those with a diverse fleet, it can be difficult to collect sufficient data to improve maintenance programs. At the same time, new rules such as entity in charge of maintenance – ECM – regulations impose an additional workload by requiring a dedicated maintenance management system and specific reports. The RailCrowd platform sets out to facilitate compliance with ECM and similar regulations while at the same time pooling anonymised fleet data across operators to form virtual fleets, providing greater data insights. Y1 - 2018 SN - 0948-7263 IS - 9 SP - 11 EP - 13 PB - Bahn-Fachverlag CY - Berlin ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin A1 - Kaesling, Katharina T1 - Family Law and Culture in Europe: Developments, Challenges and Opportunities – Konferenz der Commission on European Family Law vom 29.-31. August 2013, Bonn JF - Zeitschrift für Europäisches Privatrecht (ZEuP) N2 - Vor dem Hintergrund zunehmender gesellschaftlicher Veränderungen bei den Lebens- und Familienformen hat es sich die Commission on European Family Law (CEFL) seit 2001 zum Ziel gesetzt, unverbindliche Regelungsvorschläge für ein europaweit einheitliches Familienrecht zu schaffen. Die Vorstellung und Diskussion dieser auf rechtsvergleichender Basis erstellten Principles erfolgt auf den regelmäßig veranstalteten Tagungen der CEFL. Die nunmehr fünfte Konferenz zum Thema „Family Law and Culture in Europe – Developments, Challenges and Opportunities“ fand erstmals in Deutschland statt. Ausgerichtet wurde die Veranstaltung, zu der ca. 200 Teilnehmerinnen und Teilnehmern aus Wissenschaft und Praxis aus insgesamt 33 Ländern angereist waren, von Nina Dethloff (Direktorin des Instituts für Deutsches, Europäisches und Internationales Familienrecht an der Universität Bonn), Katharina Boele-Woelki (Direktorin des Utrecht Centre for European Research into Family Law und Preisträgerin des Anneliese Maier-Forschungspreises der Alexander von Humboldt-Stiftung) und Werner Gephart (Direktor des Käte Hamburger Kollegs „Recht als Kultur“). Y1 - 2014 SN - 0943-3929 IS - 3 SP - 673 EP - 676 PB - Beck CY - München ER - TY - JOUR A1 - Babilon, Katharina A1 - Wilbring, Daniela A1 - Tappert, Tim A1 - Pfaff, Raphael A1 - Enning, Manfred T1 - Schienenfahrzeugtechnik hands on – FH Aachen IMechE Railway Challenge JF - Ingenieurspiegel Y1 - 2018 SN - 1868-5919 IS - 2 SP - 20 EP - 22 PB - Public Verlag CY - Bingen ER - TY - JOUR A1 - Klocke, Martina A1 - Richert, Vera A1 - Sube, Maike T1 - Vier Jahre „Guter Studienstart im Ingenieurbereich“: Entwicklung und Perspektiven des „Nullten Semesters“ in Aachen JF - Zeitschrift für Beratung und Studium N2 - Bereits 2015 wurde in der Zeitschrift „Qualität in der Wissenschaft“ (QiW) über das Kooperationsprojekt „Guter Studienstart im Ingenieurbereich“, das Orientierungssemester von RWTH und FH Aachen, berichtet. In diesem Artikel legen wir den Schwerpunkt auf die Entwicklung des Projekts in den Jahren 2015 bis 2018 und geben eine Rückschau sowie einen Ausblick auf die Entwicklungsperspektiven nach dem offiziellen Projektende. Y1 - 2018 SN - 1860-3068 VL - 13 IS - 1 SP - 17 EP - 22 PB - Universitätsverlag Webler CY - Bielefeld ER - TY - JOUR A1 - Bernecker, Andreas T1 - Divided Government and the Adoption of Economic Reforms JF - CESifo DICE Report - Journal for Institutional Comparison Y1 - 2014 SN - 1612-0663 VL - 12 IS - 4 SP - 47 EP - 52 PB - Ifo Institute for Economic Research CY - München ER - TY - JOUR A1 - Bernecker, Andreas T1 - Do politicians shirk when reelection is certain? Evidence from the German parliament JF - European Journal of Political Economy N2 - Does stiffer electoral competition reduce political shirking? For a micro-analysis of this question, I construct a new data set spanning the years 2005 to 2012 covering biographical and political information about German Members of Parliament (MPs), including their attendance rates in voting sessions. For the parliament elected in 2009, I show that indeed opposition party MPs who expect to face a close race in their district show significantly and relevantly lower absence rates in parliament beforehand. MPs of governing parties seem not to react significantly to electoral competition. These results are confirmed by an analysis of the parliament elected in 2005, by several robustness checks, and also by employing an instrumental variable strategy exploiting convenient peculiarities of the German electoral system. The study also shows how MPs elected via party lists react to different levels of electoral competition. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.ejpoleco.2014.07.001 SN - 0176-2680 VL - 36 SP - 55 EP - 70 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bernecker, Andreas T1 - Divided we reform? Evidence from US welfare policies JF - Journal of Public Economics N2 - Divided government is often thought of as causing legislative deadlock. I investigate the link between divided government and economic reforms using a novel data set on welfare reforms in US states between 1978 and 2010. Panel data regressions show that, under divided government, a US state is around 25% more likely to adopt a welfare reform than under unified government. Several robustness checks confirm this counter-intuitive finding. Case study evidence suggests an explanation based on policy competition between governor, senate, and house. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.jpubeco.2016.08.003 SN - 0047-2727 VL - 142 SP - 24 EP - 38 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kearney, D. A1 - Herrmann, Ulf A1 - Nava, P. A1 - Kelly, B. A1 - Mahoney, R. A1 - Pacheco, J. A1 - Cable, R. A1 - Potrovitza, N. A1 - Blake, D. A1 - Price, H. T1 - Assessment of a Molten Salt Heat Transfer Fluid in a Parabolic Trough Solar Field JF - Journal of Solar Energy Engineering Y1 - 2003 U6 - http://dx.doi.org/10.1115/1.1565087 SN - 1528-8986 VL - 125 IS - 2 SP - 170 EP - 176 ER - TY - JOUR A1 - Hüning, Felix T1 - Nachrüstmöglichkeiten von Dieselfahrzeugen aus technischer Sicht JF - Zeitschrift für Verkehrsrecht : NZV Y1 - 2019 IS - 1 SP - 27 EP - 32 PB - C.H.Beck ER - TY - JOUR A1 - Bernecker, Andreas A1 - Klier, Julia A1 - Stern, Sebastian A1 - Thiel, Lea T1 - Sustaining high performance beyond public-sector pilot projects. Y1 - 2018 IS - September 2018 ER - TY - JOUR A1 - Richter, Charlotte A1 - Braunstein, Bjoern A1 - Winnard, Andrew A1 - Nasser, Mona A1 - Weber, T. T1 - Human Biomechanical and Cardiopulmonary Responses to Partial Gravity – A Systematic Review JF - Frontiers in physiology Y1 - 2017 U6 - http://dx.doi.org/10.3389/fphys.2017.00583 IS - 8, article 583 ER - TY - JOUR A1 - Rupp, Matthias A1 - Handschuh, Nils A1 - Rieke, Christian A1 - Kuperjans, Isabel T1 - Contribution of country-specific electricity mix and charging time to environmental impact of battery electric vehicles: A case study of electric buses in Germany JF - Applied Energy Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.apenergy.2019.01.059 SN - 0306-2619 VL - 237 SP - 618 EP - 634 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hirsch, Marko A1 - Kleeberg, Jochen A1 - Schmitz, Philipp T1 - Dynamische Asset-Allocation- Strategien im Niedrigzinsumfeld JF - Absolut|report : neue Perspektiven für institutionelle Investoren Y1 - 2018 IS - 6 SP - 52 PB - Absolut Research CY - Hamburg ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anmerkung zu OLG München: Erbscheinserteilung nach Eintritt des Nacherbfalls, Beschl. v. 1.10.2014 - Wx 314/14 JF - DNotZ - Deutsche Notar-Zeitschrift Y1 - 2015 SN - 0340-8604 IS - 5 SP - 385 EP - 390 PB - Beck CY - München ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anmerkung zu EuGH, Urt. v. 9.9.2015, Rs. C-4/14 Christophe Bohez v. Ingrid Wiertz JF - GRP : Zeitschrift für das Privatrecht der Europäischen Union N2 - Die Entscheidung in der Rechtssache Bohez /Wiertz bot dem EuGH Gelegenheit, zur Abgrenzung der Anwendungsbereiche von Brüssel I-(jetzt: Brüssel Ia-) und Brüssel IIa-VO Stellung zu nehmen. Den Ausgangspunkt bildete dabei ein familienrechtlicher Sachverhalt, nämlich die zwangsweise Durchsetzung des Umgangsrechts eines Vaters im Hinblick auf seine beiden Kinder. Auf den ersten Blick lag daher eine Anwendung der auf Verfahren betreffend die elterliche Verantwortung bezogenen Brüssel IIa-VO nahe. Andererseits schien auch eine Argumentation denkbar, wonach es sich bei dem zu vollstreckenden Anspruch auf Zahlung des Zwangsgeldes um eine Geldforderung handele, deren Vollstreckung nach der Brüssel I-VO zu erfolgen habe. Was vordergründig die Ermittlung des einschlägigen EU-Rechtsaktes betraf, erwies sich bei genauerer Betrachtung als Bestimmung der dogmatischen Rechtsnatur des Zwangsgeldes. Y1 - 2016 U6 - http://dx.doi.org/10.9785/gpr-2016-0509 SN - 2193-9519 IS - 5 SP - 255 EP - 258 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anforderungen des Unionsrechts an die standardisierte Darstellung des Namens : Anmerkung zu EuGH, Urt. v. 2. Oktober 2014, Rs. C-101/13 - Stadt Karlsruhe JF - GRP : Zeitschrift für das Privatrecht der Europäischen Union Y1 - 2015 SN - 2193-9519 IS - 6 SP - 282 EP - 285 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anmerkung zu EuGH, Urt. v. 26. April 2012, Rs. C-92/12 PPU - Health Service Executive JF - GRP : Zeitschrift für das Privatrecht der Europäischen Union Y1 - 2013 SN - 2193-9519 IS - 1 SP - 46 EP - 49 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anmerkung zu EuGH, Urt. v. 22. 12. 2010, Rs. C-208/09 - Sayn-Wittgenstein JF - GPR : Zeitschrift für das Privatrecht der Europäischen Union Y1 - 2011 U6 - http://dx.doi.org/10.1515/gpr.2011.8.5.242 SN - 2193-9519 IS - 5 SP - 242 EP - 245 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anmerkung zu EuGH, Urt. v. 1.3.2011, Rs. C-236/09 Association belge des Consomma-teurs Test-Achats JF - JuristenZeitung (JZ) Y1 - 2011 U6 - http://dx.doi.org/10.1628/002268811796448996 SN - 1868-7067 VL - 66 IS - 14 SP - 734 EP - 737 PB - Mohr Siebeck CY - Tübingen ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Anmerkung zu EuGH, Urt. v. 14.10.2008, Rs. C-353/06 Grunkin und Paul ./. Standesamt Niebüll JF - JuristenZeitung (JZ) Y1 - 2009 U6 - http://dx.doi.org/10.1628/002268809787360257 SN - 1868-7067 VL - 64 IS - 3 SP - 153 EP - 155 PB - Mohr Siebeck CY - Tübingen ER - TY - JOUR A1 - Berg, Alexander-Karl A1 - Schleser, Markus A1 - Delidovich, Artem A1 - Houben, Alexander T1 - Ultraschallunterstützter Schmelzklebstoffauftrag JF - adhäsion KLEBEN & DICHTEN Y1 - 2018 U6 - http://dx.doi.org/10.1007/s35145-018-0089-z VL - Volume 62 IS - Issue 12 SP - 32 EP - 37 PB - Springer ER - TY - JOUR A1 - Finger, Felix A1 - Braun, Carsten A1 - Bil, Cees T1 - Impact of electric propulsion technology and mission requirements on the performance of VTOL UAVs JF - CEAS Aeronautical Journal N2 - One of the engineering challenges in aviation is the design of transitioning vertical take-off and landing (VTOL) aircraft. Thrust-borne flight implies a higher mass fraction of the propulsion system, as well as much increased energy consumption in the take-off and landing phases. This mass increase is typically higher for aircraft with a separate lift propulsion system than for aircraft that use the cruise propulsion system to support a dedicated lift system. However, for a cost–benefit trade study, it is necessary to quantify the impact the VTOL requirement and propulsion configuration has on aircraft mass and size. For this reason, sizing studies are conducted. This paper explores the impact of considering a supplemental electric propulsion system for achieving hovering flight. Key variables in this study, apart from the lift system configuration, are the rotor disk loading and hover flight time, as well as the electrical systems technology level for both batteries and motors. Payload and endurance are typically used as the measures of merit for unmanned aircraft that carry electro-optical sensors, and therefore the analysis focuses on these particular parameters. Y1 - 2018 U6 - http://dx.doi.org/10.1007/s13272-018-0352-x SN - 1869-5582 print SN - 1869-5590 online VL - 10 IS - 3 SP - 843 PB - Springer ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Stärkung der Parteiautonomie durch die Europäischen Güterrechtsverordnungen JF - Neue Zeitschrift für Familienrecht - NZFam N2 - Mit der Verabschiedung der Europäischen Güterrechtsverordnung für Ehegatten und eingetragene Partner hat der Unionsgesetzgeber die Vereinheitlichung des Kollisionsrechts in Europa weiter vorangetrieben. Zentraler Baustein beider Rechtsakte ist die Parteiautonomie, die mit Blick auf Eheleute an bewährte Traditionen anknüpft, für Lebenspartner aber eine echte Neuerung bringt. Y1 - 2016 SN - 2198-2333 VL - 3 IS - 23 SP - 1061 EP - 1065 PB - Beck CY - München ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Rechtswahl und Gerichtsstandsvereinbarungen nach der Europäischen Erbrechtsverordnung JF - Notar : Monatsschrift für die gesamte notarielle Praxis Y1 - 2016 IS - 3 SP - 75 EP - 85 PB - DNotV-Verl. CY - Berlin ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Eckpunkte aktueller Reformen im Familienrecht JF - Bonner Rechtsjournal Y1 - 2009 IS - 1 SP - 25 EP - 30 PB - BRJ CY - Bonn ER - TY - JOUR A1 - Engel, Mareike A1 - Holtmann, Dirk A1 - Ulber, Roland A1 - Tippkötter, Nils T1 - Increased Biobutanol Production by Mediator‐Less Electro‐Fermentation JF - Biotechnology Journal N2 - A future bio-economy should not only be based on renewable raw materials but also in the raise of carbon yields of existing production routes. Microbial electrochemical technologies are gaining increased attention for this purpose. In this study, the electro-fermentative production of biobutanol with C. acetobutylicum without the use of exogenous mediators is investigated regarding the medium composition and the reactor design. It is shown that the use of an optimized synthetic culture medium allows higher product concentrations, increased biofilm formation, and higher conductivities compared to a synthetic medium supplemented with yeast extract. Moreover, the optimization of the reactor system results in a doubling of the maximum product concentrations for fermentation products. When a working electrode is polarized at −600 mV vs. Ag/AgCl, a shift from butyrate to acetone and butanol production is induced. This leads to an increased final solvent yield of Yᴀᴃᴇ = 0.202 gg⁻¹ (control 0.103 gg⁻¹), which is also reflected in a higher carbon efficiency of 37.6% compared to 23.3% (control) as well as a fourfold decrease in simplified E-factor to 0.43. The results are promising for further development of biobutanol production in bioelectrochemical systems in order to fulfil the principles of Green Chemistry. Y1 - 2018 U6 - http://dx.doi.org/10.1002/biot.201800514 SN - 1860-7314 IS - Volume 14, Issue 4 SP - Artikel 1800514 PB - Wiley-VCH ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Die Zukunft des verbraucherschützenden Widerrufsrechts in Europa JF - Zeitschrift für europäisches Privatrecht : ZEuP N2 - Das verbraucherschützende Widerrufsrecht ist in die Jahre gekommen. Als Ergebnis der zunehmenden Rechtszersplitterung im europäischen Richtlinienrecht hat sich eine unüberschaubare Bandbreite an Ausgestaltungsformen in den mitgliedstaatlichen Rechtssystemen herausgebildet. Effektivitätseinbußen, Wettbewerbsverzerrungen und ein hohes Maß an Rechtsunsicherheit sind die Folgen. Zurückführen lässt sich die kostenintensive Fragmentierung des Verbrauchervertragsrechts auf die bisherige Regelungspolitik der Mindestharmonisierung, die es den Mitgliedstaaten erlaubt, von dem durch die Richtlinien gesetzten Mindeststandard durch „überschießende Umsetzung” abzuweichen. Der Unionsgesetzgeber versucht dem vermehrt durch einen Prozess der Vollharmonisierung zu begegnen: Neben Reformen der Richtlinie über Verbraucherkredite (VerbrKrRL) sowie der Timesharing-Richtlinie (TimesharingRL), liegt seit dem 8. Oktober 2008 nunmehr auch der Entwurf einer Rahmenrichtlinie über die Rechte der Verbraucher (VRRL-E) vor. Danach sollen die bisherigen Richtlinien über Haustürgeschäfte (HaustürgeschäfteRL), Fernabsatzverträge (FARL), missbräuchliche Klauseln sowie Verbrauchsgüterkäufe vereinigt werden. Für das verbraucherschützende Widerrufsrecht ist damit zum einen die Herausbildung einheitlicher Kernelemente verbunden, zum anderen tritt es in Konkurrenz zu umfassenden Informationspflichten, die ebenfalls den Schutz des Verbrauchers vor dem unüberlegten Abschluss riskanter bzw. nachteiliger Verträge zum Ziel haben. Angesichts dieser Entwicklung stellt sich im Folgenden die Frage nach der Zukunft des unionsrechtlichen Widerrufsrechts. Von besonderer Bedeutung ist dabei die Klärung des Verhältnisses zu den verbraucherschützenden Informationspflichten. Dazu bedarf es zunächst der Herausarbeitung einheitlicher Kernelemente des Widerrufsrechts im vollharmonisierten Richtlinienrecht (II.) sowie einer Systematisierung der sekundärrechtlichen Informationspflichten im Anschluss eine kritische Gegenüberstellung der Vor- und Nachteile beider Schutzinstrumente erfolgen kann (IV.). Y1 - 2010 SN - 0943-3929 VL - 18 IS - 3 SP - 509 EP - 534 PB - Beck CY - München ER - TY - JOUR A1 - Dethloff, Nina A1 - Kroll-Ludwigs, Kathrin T1 - A Lei de Parceria Registrada de 2001 e suas Reformas no Direito Alemao JF - Revista Brasileira de Direito das Famílias e Sucessoes Y1 - 2009 VL - 11 IS - 12 SP - 80 EP - 94 ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Hinkende Namensrechtsverhältnisse im Fokus der gemeinschaftsrechtlichen Freizügigkeit JF - Zeitschrift für vergleichende Rechtswissenschaft (ZVglRWiss) Y1 - 2008 SN - 0044-3638 IS - 3 SP - 320 EP - 341 ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Vertragserfüllung als zeitliche Grenze des verbraucherschützenden Widerrufsrechts JF - Neue Juristische Wochenschrift (NJW) Y1 - 2008 SN - 0341-1907 VL - 61 IS - 28 SP - 1999 EP - 2002 ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin A1 - Ludwigs, Markus T1 - Die richtlinienkonforme Rechtsfortbildung im Gesamtsystem der Richtlinienwirkungen Zugleich Besprechung von BGH, Urt. v. 26.11.2008 – VIII ZR 200/05 (Quelle) [Teil 2] JF - Zeitschrift für das juristische Studium / ZJS Y1 - 2009 SN - 1865-6331 VL - 2 IS - 2 SP - 123 EP - 130 PB - T. Rotsch CY - Gießen ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin A1 - Ludwigs, Markus T1 - Die richtlinienkonforme Rechtsfortbildung im Gesamtsystem der Richtlinienwirkungen : Zugleich Besprechung von BGH, Urt. v. 26.11.2008 – VIII ZR 200/05 (Quelle) [Teil 1] JF - Zeitschrift für das juristische Studium / ZJS Y1 - 2009 SN - 1865-6331 VL - 2 IS - 1 SP - 7 EP - 14 PB - T. Rotsch CY - Gießen ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Ein optionales Vertragsrecht für Europa: Motor oder Hemmnis für den Binnenmarkt? JF - GPR : Zeitschrift für Gemeinschaftsprivatrecht Y1 - 2018 U6 - http://dx.doi.org/10.1515/gpr.2012.9.4.181 SN - 2193-9519 VL - 9 IS - 4 SP - 181 EP - 188 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Dethloff, Nina A1 - Kroll-Ludwigs, Kathrin T1 - The Constitutional Court as Driver of Reforms in German Family Law JF - International Survey of Family Law Y1 - 2018 SP - 217 EP - 234 ER - TY - JOUR A1 - Dethloff, Nina A1 - Kroll-Ludwigs, Kathrin T1 - Strengthening Children's Rights in German Family Law JF - The International Survey of Family Law Y1 - 2018 SP - 119 EP - 136 ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - The Reform of German Maintenance Law JF - The International Survey of Family Law Y1 - 2018 SP - 85 EP - 100 ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Das Verhältnis von Haager Unterhaltsprotokoll (2007) und Haager Unterhalts-übereinkommen (1973): lex posterior derogat legi priori? JF - IPRax : Praxis des internationalen Privat- und Verfahrensrechts N2 - In der EU richtet sich das auf unterhaltsrechtliche Sachverhalte mit grenzüberschreitendem Bezug anwendbare Recht seit dem 18. Juni 2011 nach dem Haager Protokoll über das auf Unterhaltspflichten anwendbare Recht vom 23. November 2007 („HUP“). Dieser Rechtsakt, der EU-weit anwendbar ist, hat das Haager Unterhaltsübereinkommen von 1973 („HUÜ“) ersetzt und das Unterhaltskollisionsrecht in der EU auf eine neue, einheitliche Grundlage gestellt. Bei den Vorschriften des HUP handelt es sich um sog. lois universelles, die unabhängig davon gelten, welche Staatsangehörigkeit die unterhaltsberechtigte bzw. die unterhaltsverpflichtete Person haben. Zu beachten ist aber, dass die Bundesrepublik Deutschland ebenso wie die Türkei, die Schweiz, Japan und Albanien das HUÜ ratifiziert hatten. Für die Nicht-EU-Staaten besteht aber keine Bindung an die Vorschriften des HUP, so dass sich im Verhältnis zu ihnen die Frage stellt, ob das HUÜ weiterhin Anwendung finden kann. Die Problematik ist gerade im Hinblick auf die erweiterten Rechtswahlmöglichkeiten des HUP von erheblicher praktischer Relevanz. Y1 - 2016 SN - 0720-6585 VL - 36 IS - 1 SP - 34 EP - 40 PB - Gieseking CY - Bielefeld ER - TY - JOUR A1 - Kampker, Achim A1 - Schleser, Markus A1 - Triebs, Johannes A1 - Berg, Alexander-Karl A1 - Hansen, Jan Ole A1 - Fiedler, Falko T1 - Bauteilintegrierte Vorrichtungsfunktionen im Karosseriebau : Aktuelle Ergebnisse im Forschungsprojekt ProeK JF - ZWF Zeitschrift für wirtschaftlichen Fabrikbetrieb N2 - Das Forschungsprojekt Produktionseffizienz in der Kleinserie (ProeK) erarbeitet kostengünstige und effiziente Lösungsansätze für Prozessketten im Zukunftsfeld der Elektromobilität. Das Teilprojekt Karosserie setzt diese Zielsetzung durch innovative und praxisorientierte Produkt- und Prozesskonzepte mit neuartigen bauteilintegrierten Vorrichtungsfunktionen (BiV) um. Im Teilprojekt Außenhaut sollen Toleranzen adaptiv durch Anpassungen der Prozessparameter sowie Bauteilmanipulation kompensiert werden. Y1 - 2018 U6 - http://dx.doi.org/10.3139/104.112012 SN - 0947-0085 VL - 113 IS - 11 SP - 767 EP - 770 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Kroll-Ludwigs, Kathrin T1 - Vereinheitlichung des Güterkollisionsrechts in Europa – die EU-Ehegüterrechts- und EU-Partnerschaftsverordnung (Teil 1) JF - GPR: Zeitschrift für das Privatrecht der Europäischen Union N2 - Zehn Jahre nach Erlass des „Grünbuchs zu den Kollisionsnormen im Güterrecht“ vom 17.7.2006 hat der Rat der Europäischen Union am 24.6.2016 die EU-Ehegüterrechts-(„EuGüVO“) sowie die EU-Partnerschaftsverordnung („EuPartVO“) erlassen. Damit wird das europäische Güterkollisionsrecht fü rca. 16 Millionen „internationaler Paare“ in der EU auf eine neue, einheitliche Grundlage gestellt. Anders als ursprünglich geplant, handelt es sich bei beiden Verordnungen nicht um gesamteuropäische Rechtsakte, da die für Art. 81 Abs. 3 AEUV erforderliche Einstimmigkeit unter den Mitgliedstaaten letztlich nicht erreicht werden konnte. Das Scheitern der ersten Verordnungsvorschläge aus dem Jahr 2011 war dabei dem Umstand geschuldet, dass rechtspolitisch von Anfang an eine Verknüpfung beider Regelungsmaterien gewollt war. Mit Blick auf die Einführung einheitlicher güterrechtlicher Regelungen für eingetragene Partnerschaften war aber nicht nur das „Ob“ und „Wie“ etwaiger Rechtswahlmöglichkeiten heftig umstritten. Insbesondere diejenigen Mitgliedstaaten, die dem Rechtsinstitut der eingetragenen Lebenspartnerschaft kritisch gegenüberstehen, sahen in der Einführung einheitlicher Kollisionsnormen die Gefahr einer zwangsweisen Durchsetzung dieses Rechtsinstituts „durch die Hintertür“. Vor diesem Hintergrund erwies sich – ebenso wie schon bei der Rom III-VO – das Verfahren zur verstärkten Zusammenarbeit(Art. 20 EUV i.V.m. Art. 326 ff. AEUV) als probates Mittel, um den Integrationsprozess im Bereich des europäischen Kollisionsrechts voranzutreiben. Achtzehn Mitgliedstaaten nehmen an dieser Verstärkten Zusammenarbeit teil. Y1 - 2016 U6 - http://dx.doi.org/10.9785/gpr-2016-0509 SN - 2193-9519 VL - 13 IS - 5 SP - 231 EP - 241 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Kramer, Matthias A1 - Valero, Daniel A1 - Chanson, Hubert A1 - Bung, Daniel B. T1 - Towards reliable turbulence estimations with phase-detection probes: an adaptive window cross-correlation technique JF - Experiments in Fluids Y1 - 2019 U6 - http://dx.doi.org/10.1007/s00348-018-2650-9 SN - 1432-1114 VL - 60 EP - Article number 2 PB - Springer CY - Berlin ER -