TY  - JOUR
A1  - Baringhaus, Ludwig
A1  - Gaigall, Daniel
T1  - On Hotelling’s T² test in a special paired sample case
JF  - Communications in Statistics - Theory and Methods
N2  - In a special paired sample case, Hotelling’s T² test based on the differences of the paired random vectors is the likelihood ratio test for testing the hypothesis that the paired random vectors have the same mean; with respect to a special group of affine linear transformations it is the uniformly most powerful invariant test for the general alternative of a difference in mean. We present an elementary straightforward proof of this result. The likelihood ratio test for testing the hypothesis that the covariance structure is of the assumed special form is derived and discussed. Applications to real data are given.
KW  - complete block symmetry
KW  - Hotelling’s T² test
KW  - likelihood ratio test
KW  - uniformly most powerful invariant test
Y1  - 2017
U6  - https://doi.org/10.1080/03610926.2017.1408828
SN  - 1532-415X
VL  - 48
IS  - 2
SP  - 257
EP  - 267
PB  - Taylor & Francis
CY  - London
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  - https://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  - Block, Simon
A1  - Viebahn, Peter
A1  - Jungbluth, Christian
T1  - Analysing direct air capture for enabling negative emissions in Germany: an assessment of the resource requirements and costs of a potential rollout in 2045
JF  - Frontiers in Climate
N2  - Direct air capture (DAC) combined with subsequent storage (DACCS) is discussed as one promising carbon dioxide removal option. The aim of this paper is to analyse and comparatively classify the resource consumption (land use, renewable energy and water) and costs of possible DAC implementation pathways for Germany. The paths are based on a selected, existing climate neutrality scenario that requires the removal of 20 Mt of carbon dioxide (CO2) per year by DACCS from 2045. The analysis focuses on the so-called “low-temperature” DAC process, which might be more advantageous for Germany than the “high-temperature” one. In four case studies, we examine potential sites in northern, central and southern Germany, thereby using the most suitable renewable energies for electricity and heat generation. We show that the deployment of DAC results in large-scale land use and high energy needs. The land use in the range of 167–353 km2 results mainly from the area required for renewable energy generation. The total electrical energy demand of 14.4 TWh per year, of which 46% is needed to operate heat pumps to supply the heat demand of the DAC process, corresponds to around 1.4% of Germany's envisaged electricity demand in 2045. 20 Mt of water are provided yearly, corresponding to 40% of the city of Cologne‘s water demand (1.1 million inhabitants). The capture of CO2 (DAC) incurs levelised costs of 125–138 EUR per tonne of CO2, whereby the provision of the required energy via photovoltaics in southern Germany represents the lowest value of the four case studies. This does not include the costs associated with balancing its volatility. Taking into account transporting the CO2 via pipeline to the port of Wilhelmshaven, followed by transporting and sequestering the CO2 in geological storage sites in the Norwegian North Sea (DACCS), the levelised costs increase to 161–176 EUR/tCO2. Due to the longer transport distances from southern and central Germany, a northern German site using wind turbines would be the most favourable.
KW  - rollout
KW  - economics
KW  - Germany
KW  - negative emissions
KW  - carbon dioxide removal
KW  - climate neutrality
KW  - DAC
KW  - direct air capture
Y1  - 2024
U6  - https://doi.org/10.3389/fclim.2024.1353939
SN  - 2624-9553
VL  - 6
PB  - Frontiers
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Bhattarai, Aroj
A1  - Staat, Manfred
T1  - Computational comparison of different textile implants to correct apical prolapse in females
JF  - Current Directions in Biomedical Engineering
N2  - Prosthetic textile implants of different shapes, sizes and polymers are used to correct the apical prolapse after hysterectomy (removal of the uterus). The selection of the implant before or during minimally invasive surgery depends on the patient’s anatomical defect, intended function after reconstruction and most importantly the surgeon’s preference. Weakness or damage of the supporting tissues during childbirth, menopause or previous pelvic surgeries may put females in higher risk of prolapse. Numerical simulations of reconstructed pelvic floor with weakened tissues and organ supported by textile product models: DynaMesh®-PRS soft, DynaMesh®-PRP soft and DynaMesh®-CESA from FEG Textiletechnik mbH, Germany are compared.
Y1  - 2018
U6  - https://doi.org/10.1515/cdbme-2018-0159
VL  - 4
IS  - 1
SP  - 661
EP  - 664
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Bragard, Michael
A1  - Conrad, M.
A1  - van Hoek, H.
A1  - De Doncker, R. W.
T1  - The integrated emitter turn-off thyristor (IETO) : an innovative thyristor-based high power semiconductor device using MOS assisted turn-off
JF  - IEEE transactions on industry applications
Y1  - 2011
U6  - https://doi.org/10.1109/TIA.2011.2161432
SN  - 0093-9994
VL  - 47
IS  - 5
SP  - 2175
EP  - 2182
PB  - IEEE
CY  - New York
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  - 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  - 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  - 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  - 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  -