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 - https://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 - Kleefeld, Andreas T1 - The hot spots conjecture can be false: some numerical examples JF - Advances in Computational Mathematics N2 - The hot spots conjecture is only known to be true for special geometries. This paper shows numerically that the hot spots conjecture can fail to be true for easy to construct bounded domains with one hole. The underlying eigenvalue problem for the Laplace equation with Neumann boundary condition is solved with boundary integral equations yielding a non-linear eigenvalue problem. Its discretization via the boundary element collocation method in combination with the algorithm by Beyn yields highly accurate results both for the first non-zero eigenvalue and its corresponding eigenfunction which is due to superconvergence. Additionally, it can be shown numerically that the ratio between the maximal/minimal value inside the domain and its maximal/minimal value on the boundary can be larger than 1 + 10− 3. Finally, numerical examples for easy to construct domains with up to five holes are provided which fail the hot spots conjecture as well. KW - Numerics KW - Boundary integral equations KW - Potential theory KW - Helmholtz equation KW - Interior Neumann eigenvalues Y1 - 2021 U6 - https://doi.org/10.1007/s10444-021-09911-5 SN - 1019-7168 VL - 47 PB - Springer CY - Dordrecht ER - TY - PAT A1 - Burlage, Thomas A1 - Hörauf, Martin A1 - Klandt, Michael A1 - Wahle, Michael T1 - Schwingungsdämpfer : Offenlegungsschrift T1 - Friction damper having an elastomer spring element : patent of invention Y1 - 1998 N1 - Deutscher Titel der Europäischen Patentanmeldung: Reibungsdämpfer mit einem Elastomerfederelement PB - Deutsches Patent- und Markenamt / Europäisches Patentamt CY - München / Den Hague 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 - https://doi.org/10.1124/dmd.119.086397 IS - Early view ER - TY - GEN A1 - Topcu, Murat A1 - Madabhushi, Gopal Santana Phani A1 - Staat, Manfred T1 - Datasets from FEM Simulations done with COMSOL Multiphysics and Code_Aster N2 - Datasets from FEM Simulations done with COMSOL Multiphysics and Code_Aster for an elastic stress transfer between matrix and fibres having a variable radius. KW - Natural fibres KW - Polymer-matrix composites KW - Biocomposites KW - Stress concentrations KW - Finite element analysis (FEA) Y1 - 2022 U6 - https://doi.org/10.6084/m9.figshare.19333295.v2 ER - TY - CHAP A1 - Ringbeck, Thorsten A1 - Hagebeuker, Bianca A1 - Kraft, Holger A1 - Paintner, Michael ED - Tille, Thomas T1 - PMD-basierte 3D-Optosensoren zur Fahrzeugumfelderfassung T2 - Sensoren im Automobil II : mit 27 Tabellen / [2. Tagung Sensoren im Automobil 2007] Y1 - 2007 SN - 978-3-8169-2750-1 N1 - Tagung Sensoren im Automobil <2, 2007, München> N1 - (Fachbuch ; Bd. 86) PB - expert-Verl. CY - Renningen ER - TY - JOUR A1 - Raatschen, Hans-Jürgen T1 - Fokussierung von Spannungswellen in einer krummlinig berandeten Scheibe JF - ZAMM : Zeitschrift für Angewandte Mathematik und Mechanik Y1 - 1987 SN - 1521-4001 N1 - Artikel umfasst die Seiten 11 und 12 des 30-Seiten-langen PDFs der Online-Ausgabe. VL - 67 IS - 4 SP - T230 EP - T231 ER - TY - BOOK A1 - Wahle, Michael T1 - Grundlagen der Maschinen- und Strukturdynamik. - (Höhere Technische Mechanik ; 2) Y1 - 1995 SN - 3-930911-61-2 PB - Mainz CY - Aachen ET - 1. Aufl. ER - TY - JOUR A1 - Goßmann, Matthias A1 - Frotscher, Ralf A1 - Linder, Peter A1 - Bayer, Robin A1 - Epple, U. A1 - Staat, Manfred A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard T1 - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells JF - Cellular physiology and biochemistry N2 - Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential. KW - Inotropic compounds KW - Pharmacology KW - Ion channels KW - CellDrum KW - Heart tissue culture KW - Induced pluripotent stem cells KW - Cardiac myocytes Y1 - 2016 U6 - https://doi.org/10.1159/000443124 SN - 1421-9778 (Online) SN - 1015-8987 (Print) VL - 38 IS - 3 SP - 1182 EP - 1198 PB - Karger CY - Basel ER - TY - CHAP A1 - Kahra, Marvin A1 - Breuß, Michael A1 - Kleefeld, Andreas A1 - Welk, Martin ED - Brunetti, Sara ED - Frosini, Andrea ED - Rinaldi, Simone T1 - An Approach to Colour Morphological Supremum Formation Using the LogSumExp Approximation T2 - Discrete Geometry and Mathematical Morphology N2 - Mathematical morphology is a part of image processing that has proven to be fruitful for numerous applications. Two main operations in mathematical morphology are dilation and erosion. These are based on the construction of a supremum or infimum with respect to an order over the tonal range in a certain section of the image. The tonal ordering can easily be realised in grey-scale morphology, and some morphological methods have been proposed for colour morphology. However, all of these have certain limitations. In this paper we present a novel approach to colour morphology extending upon previous work in the field based on the Loewner order. We propose to consider an approximation of the supremum by means of a log-sum exponentiation introduced by Maslov. We apply this to the embedding of an RGB image in a field of symmetric 2x2 matrices. In this way we obtain nearly isotropic matrices representing colours and the structural advantage of transitivity. In numerical experiments we highlight some remarkable properties of the proposed approach. Y1 - 2024 SN - 978-3-031-57793-2 U6 - https://doi.org/10.1007/978-3-031-57793-2_25 N1 - Third International Joint Conference, DGMM 2024, Florence, Italy, April 15–18, 2024 SP - 325 EP - 337 PB - Springer CY - Cham ER -