@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{Kleefeld2021, author = {Kleefeld, Andreas}, title = {The hot spots conjecture can be false: some numerical examples}, series = {Advances in Computational Mathematics}, volume = {47}, journal = {Advances in Computational Mathematics}, publisher = {Springer}, address = {Dordrecht}, issn = {1019-7168}, doi = {10.1007/s10444-021-09911-5}, year = {2021}, abstract = {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.}, language = {en} } @misc{BurlageHoeraufKlandtetal.1998, author = {Burlage, Thomas and H{\"o}rauf, Martin and Klandt, Michael and Wahle, Michael}, title = {Schwingungsd{\"a}mpfer : Offenlegungsschrift}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt}, address = {M{\"u}nchen / Den Hague}, pages = {14 S. : graph. Darst.}, year = {1998}, 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} } @misc{TopcuMadabhushiStaat2022, author = {Topcu, Murat and Madabhushi, Gopal Santana Phani and Staat, Manfred}, title = {Datasets from FEM Simulations done with COMSOL Multiphysics and Code_Aster}, doi = {10.6084/m9.figshare.19333295.v2}, year = {2022}, abstract = {Datasets from FEM Simulations done with COMSOL Multiphysics and Code_Aster for an elastic stress transfer between matrix and fibres having a variable radius.}, language = {en} } @incollection{RingbeckHagebeukerKraftetal.2007, author = {Ringbeck, Thorsten and Hagebeuker, Bianca and Kraft, Holger and Paintner, Michael}, title = {PMD-basierte 3D-Optosensoren zur Fahrzeugumfelderfassung}, series = {Sensoren im Automobil II : mit 27 Tabellen / [2. Tagung Sensoren im Automobil 2007]}, booktitle = {Sensoren im Automobil II : mit 27 Tabellen / [2. Tagung Sensoren im Automobil 2007]}, editor = {Tille, Thomas}, publisher = {expert-Verl.}, address = {Renningen}, isbn = {978-3-8169-2750-1}, year = {2007}, language = {de} } @article{Raatschen1987, author = {Raatschen, Hans-J{\"u}rgen}, title = {Fokussierung von Spannungswellen in einer krummlinig berandeten Scheibe}, series = {ZAMM : Zeitschrift f{\"u}r Angewandte Mathematik und Mechanik}, volume = {67}, journal = {ZAMM : Zeitschrift f{\"u}r Angewandte Mathematik und Mechanik}, number = {4}, issn = {1521-4001}, pages = {T230 -- T231}, year = {1987}, language = {de} } @book{Wahle1995, author = {Wahle, Michael}, title = {Grundlagen der Maschinen- und Strukturdynamik. - (H{\"o}here Technische Mechanik ; 2)}, edition = {1. Aufl.}, publisher = {Mainz}, address = {Aachen}, isbn = {3-930911-61-2}, pages = {216 S. : graph. Darst.}, year = {1995}, language = {de} } @article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {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.}, language = {en} } @inproceedings{KahraBreussKleefeldetal.2024, author = {Kahra, Marvin and Breuß, Michael and Kleefeld, Andreas and Welk, Martin}, title = {An Approach to Colour Morphological Supremum Formation Using the LogSumExp Approximation}, series = {Discrete Geometry and Mathematical Morphology}, booktitle = {Discrete Geometry and Mathematical Morphology}, editor = {Brunetti, Sara and Frosini, Andrea and Rinaldi, Simone}, publisher = {Springer}, address = {Cham}, isbn = {978-3-031-57793-2}, doi = {10.1007/978-3-031-57793-2_25}, pages = {325 -- 337}, year = {2024}, abstract = {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.}, language = {en} }