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  - Kämper, Klaus-Peter
A1  - Berg, U.
A1  - Wolf, A.
A1  - Lehr, H.
T1  - Entwicklung von Linsenhaltern für ein SMIF-kompatibles Magazinsystem und deren Fertigung durch Mikrospritzguß. Berg, U.; Kämper, K.-P.; Wolf, A.; Lehr, H.; Ehrfeld, W.
JF  - Produktionstechnik für Mikrosysteme. IPA-Seminar, 5. und 6. November 1996, Stuttgart. Pro Mikro. Fraunhofer-Institut für Produktionstechnik und Automatisierung -IPA-, Stuttgart
Y1  - 1996
ER  - 
TY  - CHAP
A1  - Wendorff, Marion
A1  - Eggert, Thorsten
A1  - Pohl, Martina
A1  - Dresen, Carola
A1  - Müller, Michael
A1  - Jaeger, Karl-Erich
A1  - Sprenger, Georg A.
A1  - Schürmann, Melanie
A1  - Schürmann, Martin
A1  - Johnen, Sandra
A1  - Sprenger, Gerda
A1  - Sahm, Hermann
A1  - Inoue, Tomoyuki
A1  - Schörken, Ulrich
A1  - Breittaupt, Holger
A1  - Frölich, Bettina
A1  - Heim, Petra
A1  - Iding, Hans
A1  - Juchem, Bettina
A1  - Siegert, Petra
A1  - Kula, Maria-Regina
A1  - Weckbecker, Andrea
A1  - Hummel, Werner
A1  - Fessner, Wolf-Dieter
A1  - Elling, Lothar
A1  - Wolberg, Michael
A1  - Bode, Silke
A1  - Feldmann, Ralf
A1  - Geilenkirchen, Petra
A1  - Schubert, Thomas
A1  - Walter, Lydia
A1  - Dünnwald, Thomas
A1  - Demir, Ayhan S.
A1  - Kolter-Jung, Doris
A1  - Nitsche, Adam
A1  - Dünkelmann, Pascal
A1  - Cosp, Annabel
A1  - Lingen, Bettina
T1  - Catalytic asymmetric synthesis : section 2.2
T2  - Asymmetric synthesis with chemical and biological methods / ed. by Dieter Enders ...
Y1  - 2007
SN  - 978-3-527-31473-7
SP  - 298
EP  - 413
PB  - Wiley-VCH
CY  - Weinheim
ER  - 
TY  - JOUR
A1  - Kornfeld, Jan-Wilhelm
A1  - Baitzel, Catherina
A1  - Könner, A. Christine
A1  - Nicholls, Hayley T.
A1  - Vogt, Merly C.
A1  - Herrmanns, Karolin
A1  - Scheja, Ludger
A1  - Haumaitre, Cécile
A1  - Wolf, Anna M.
A1  - Knippschild, Uwe
A1  - Seibler, Jost
A1  - Cereghini, Silvia
A1  - Heeren, Joerg
A1  - Stoffel, Markus
A1  - Brüning, Jens C.
T1  - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b
JF  - Nature
Y1  - 2013
SN  - 0028-0836
U6  - http://dx.doi.org/10.1038/nature11793
VL  - 494
IS  - 7435
SP  - 111
EP  - 115
PB  - Springer Nature
CY  - Cham
ER  - 
TY  - JOUR
A1  - Vogt, C.
A1  - Mottaghy, Darius
A1  - Rath, V.
A1  - Marquart, G.
A1  - Dijkshoorn, L.
A1  - Wolf, A.
A1  - Clauser, C.
T1  - Vertical variation in heat flow on the Kola Peninsula: palaeoclimate or fluid flow?
JF  - Geophysical Journal International
N2  - Following earlier studies, we present forward and inverse simulations of heat and fluid transport of the upper crust using a local 3-D model of the Kola area. We provide best estimates for palaeotemperatures and permeabilities, their errors and their dependencies. Our results allow discriminating between the two mentioned processes to a certain extent, partly resolving the non-uniqueness of the problem. We find clear indications for a significant contribution of advective heat transport, which, in turn, imply only slightly lower ground surface temperatures during the last glacial maximum relative to the present value. These findings are consistent with the general background knowledge of (i) the fracture zones and the corresponding fluid movements in the bedrock and (ii) the glacial history of the Kola area.
Y1  - 2014
U6  - http://dx.doi.org/10.1093/gji/ggu282
SN  - 1365-246X
VL  - 199
IS  - 2
SP  - 829
EP  - 843
PB  - Oxford University Press
CY  - Oxford
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  - 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  - 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  - 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  - 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  - Vogt, C.
A1  - Mottaghy, Darius
A1  - Wolf, A.
A1  - Rath, V.
A1  - Pechnig, R.
A1  - Clauser, C.
T1  - Reducing temperature uncertainties by stochastic geothermal reservoir modelling
JF  - Geophysical Journal International
N2  - Quantifying and minimizing uncertainty is vital for simulating technically and economically successful geothermal reservoirs. To this end, we apply a stochastic modelling sequence, a Monte Carlo study, based on (i) creating an ensemble of possible realizations of a reservoir model, (ii) forward simulation of fluid flow and heat transport, and (iii) constraining post-processing using observed state variables. To generate the ensemble, we use the stochastic algorithm of Sequential Gaussian Simulation and test its potential fitting rock properties, such as thermal conductivity and permeability, of a synthetic reference model and—performing a corresponding forward simulation—state variables such as temperature. The ensemble yields probability distributions of rock properties and state variables at any location inside the reservoir. In addition, we perform a constraining post-processing in order to minimize the uncertainty of the obtained distributions by conditioning the ensemble to observed state variables, in this case temperature. This constraining post-processing works particularly well on systems dominated by fluid flow. The stochastic modelling sequence is applied to a large, steady-state 3-D heat flow model of a reservoir in The Hague, Netherlands. The spatial thermal conductivity distribution is simulated stochastically based on available logging data. Errors of bottom-hole temperatures provide thresholds for the constraining technique performed afterwards. This reduce the temperature uncertainty for the proposed target location significantly from 25 to 12 K (full distribution width) in a depth of 2300 m. Assuming a Gaussian shape of the temperature distribution, the standard deviation is 1.8 K. To allow a more comprehensive approach to quantify uncertainty, we also implement the stochastic simulation of boundary conditions and demonstrate this for the basal specific heat flow in the reservoir of The Hague. As expected, this results in a larger distribution width and hence, a larger, but more realistic uncertainty estimate. However, applying the constraining post-processing the uncertainty is again reduced to the level of the post-processing without stochastic boundary simulation. Thus, constraining post-processing is a suitable tool for reducing uncertainty estimates by observed state variables.
Y1  - 2010
U6  - http://dx.doi.org/10.1111/j.1365-246X.2009.04498.x
SN  - 1365-246X
VL  - 181
IS  - 1
SP  - 321
EP  - 333
PB  - Oxford University Press
CY  - Oxford
ER  -