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 - https://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 - CHAP A1 - Bitz, Andreas A1 - Kraff, O. A1 - Orzada, S. A1 - Maderwald, S. A1 - Brote, I. A1 - Johst, S. A1 - Ladd, E. T1 - Assessment of RF Safety of Transmit Coils at 7 Tesla by Experimental and Numerical Procedures (490.) T2 - 19th annual ISMRM scientific meeting and exhibition 2011 : Montreal, Quebec, Canada, 7 - 13 May 2011 Y1 - 2012 SN - 978-1-61839-284-8 IS - Volume 1 SP - 475 PB - Curran CY - Red Hook, NY ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Kong, Shushu A1 - Arciszewski, Pawel A1 - Wielbalck, Swantje A1 - Abram, Ulrich T1 - Aryl and NHC Compounds of Technetium and Rhenium JF - Journal of the American Chemical Society N2 - Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh2(PPh3)2] is formed by the reaction of [TcNCl2(PPh3)2] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh2(HLPh)2], where HLPh is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu4)[TcNCl4] and HLPh or its methoxo-protected form. The latter compound allows the comparison of different Tc–C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate. Y1 - 2012 U6 - https://doi.org/10.1021/ja3033718 SN - 1520-5126 VL - 134 IS - 22 SP - 9118 EP - 9121 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Ngyugen, Hung Huy A1 - Kahlcke, Nils A1 - Deflon, Victor M. A1 - Abram, Ulrich T1 - Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines JF - Polyhedron N2 - N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core. Y1 - 2012 U6 - https://doi.org/10.1016/j.poly.2012.04.008 SN - 0277-5387 VL - 40 IS - 1 SP - 153 EP - 158 PB - Elsevier CY - Amsterdam ER - TY - THES A1 - Oflaz, Hakan T1 - Entwicklung eines Prototypen zur Prognose von Frühgeburten : ein biomedizintechnischer Ansatz Y1 - 2012 U6 - https://doi.org/10.4126/38m-004639208 N1 - Köln, Univ., Diss., 2012 PB - Deutsche Zentralbibliothek für Medizin CY - Köln ER - TY - THES A1 - Kurulgan Demirci, Eylem T1 - The effect of rhAPC on contractile tension : an in-vitro sepsis model of cardiomyocytes and endothelial cells T1 - Der Effekt von rhAPC auf die zelluläre Kontraktionskraft : ein In-vitro-Sepsismodell für Kardiomyozyten und Endothelzellen Y1 - 2012 N1 - Aachen, Techn. Hochsch., Diss., 2012 ER - TY - JOUR A1 - Czarnecki, Christian A1 - Spiliopoulou, Myra T1 - A holistic framework for the implementation of a next generation network JF - International Journal of Business Information Systems N2 - As the potential of a next generation network (NGN) is recognised, telecommunication companies consider switching to it. Although the implementation of an NGN seems to be merely a modification of the network infrastructure, it may trigger or require changes in the whole company, because it builds upon the separation between service and transport, a flexible bundling of services to products and the streamlining of the IT infrastructure. We propose a holistic framework, structured into the layers ‘strategy’, ‘processes’ and ‘information systems’ and incorporate into each layer all concepts necessary for the implementation of an NGN, as well as the alignment of these concepts. As a first proof-of-concept for our framework we have performed a case study on the introduction of NGN in a large telecommunication company; we show that our framework captures all topics that are affected by an NGN implementation. KW - next generation network KW - telecommunication KW - NGN KW - IP-based networks KW - product bundling Y1 - 2012 U6 - https://doi.org/10.1504/IJBIS.2012.046291 SN - 1746-0972 VL - 9 IS - 4 SP - 385 EP - 401 PB - Inderscience Enterprises CY - Olney, Bucks ER - TY - BOOK A1 - Gell, Sebastian T1 - Determinants of earnings forecast error, earnings forecast revision and earnings forecast accuracy N2 - ​Earnings forecasts are ubiquitous in today’s financial markets. They are essential indicators of future firm performance and a starting point for firm valuation. Extremely inaccurate and overoptimistic forecasts during the most recent financial crisis have raised serious doubts regarding the reliability of such forecasts. This thesis therefore investigates new determinants of forecast errors and accuracy. In addition, new determinants of forecast revisions are examined. More specifically, the thesis answers the following questions: 1) How do analyst incentives lead to forecast errors? 2) How do changes in analyst incentives lead to forecast revisions?, and 3) What factors drive differences in forecast accuracy? Y1 - 2012 SN - 978-3-8349-3936-4 SN - 978-3-8349-3937-1 U6 - https://doi.org/10.1007/978-3-8349-3937-1 N1 - Titel in der Buchreihe: Quantitatives Controlling PB - Springer Gabler CY - Wiesbaden ER - TY - JOUR A1 - Orzada, S. A1 - Maderwald, S. A1 - Poser, B. A. A1 - Johst, S. A1 - Kannengiesser, S. A1 - Ladd, M. E. A1 - Bitz, Andreas T1 - Time-interleaved acquisition of modes: an analysis of SAR and image contrast implications JF - Magnetic Resonance in Medicine N2 - s the magnetic field strength and therefore the operational frequency in MRI are increased, the radiofrequency wavelength approaches the size of the human head/body, resulting in wave effects which cause signal decreases and dropouts. Especially, whole-body imaging at 7 T and higher is therefore challenging. Recently, an acquisition scheme called time-interleaved acquisition of modes has been proposed to tackle the inhomogeneity problems in high-field MRI. The basic premise is to excite two (or more) different Burn:x-wiley:07403194:media:MRM23081:tex2gif-stack-1 modes using static radiofrequency shimming in an interleaved acquisition, where the complementary radiofrequency patterns of the two modes can be exploited to improve overall signal homogeneity. In this work, the impact of time-interleaved acquisition of mode on image contrast as well as on time-averaged specific absorption rate is addressed in detail. Time-interleaved acquisition of mode is superior in Burn:x-wiley:07403194:media:MRM23081:tex2gif-stack-2 homogeneity compared with conventional radiofrequency shimming while being highly specific absorption rate efficient. Time-interleaved acquisition of modes can enable almost homogeneous high-field imaging throughout the entire field of view in PD, T2, and T2*-weighted imaging and, if a specified homogeneity criterion is met, in T1-weighted imaging as well. Y1 - 2012 U6 - https://doi.org/10.1002/mrm.23081 SN - 1522-2594 VL - 67 IS - 4 SP - 1033 EP - 1041 PB - Wiley-Liss CY - New York ER - TY - JOUR A1 - Kobus, Thiele A1 - Bitz, Andreas A1 - Uden, Mark J. van A1 - Lagemaat, Miram W. A1 - Rothgang, Eva A1 - Orzada, Stephan A1 - Heerschap, Arend A1 - Scheenen, Tom W. J. T1 - In vivo 31P MR spectroscopic imaging of the human prostate at 7 T: safety and feasibility JF - Magnetic Resonance in Medicine N2 - 31P MR spectroscopic imaging of the human prostate provides information about phosphorylated metabolites that could be used for prostate cancer characterization. The sensitivity of a magnetic field strength of 7 T might enable 3D 31P MR spectroscopic imaging with relevant spatial resolution in a clinically acceptable measurement time. To this end, a 31P endorectal coil was developed and combined with an eight-channel 1H body-array coil to relate metabolic information to anatomical location. An extensive safety validation was performed to evaluate the specific absorption rate, the radiofrequency field distribution, and the temperature distribution of both coils. This validation consisted of detailed Finite Integration Technique simulations, confirmed by MR thermometry and Burn:x-wiley:07403194:media:MRM24175:tex2gif-stack-1 measurements in a phantom and in vivo temperature measurements. The safety studies demonstrated that the presence of the 31P endorectal coil had no influence on the specific absorption rate levels and temperature distribution of the external eight-channel 1H array coil. To stay within a 10 g averaged local specific absorption rate of 10 W/kg, a maximum time-averaged input power of 33 W for the 1H array coil was allowed. For transmitting with the 31P endorectal coil, our safety limit of less than 1°C temperature increase in vivo during a 15-min MR spectroscopic imaging experiment was reached at a time-averaged input power of 1.9 W. With this power setting, a second in vivo measurement was performed on a healthy volunteer. Using adiabatic excitation, 3D 31P MR spectroscopic imaging produced spectra from the entire prostate in 18 min with a spatial resolution of 4 cm3. The spectral resolution enabled the separate detection of phosphocholine, phosphoethanolamine, inorganic phosphate, and other metabolites that could play an important role in the characterization of prostate cancer. Y1 - 2012 U6 - https://doi.org/10.1002/mrm.24175 SN - 1522-2594 VL - 68 IS - 6 SP - 1683 EP - 1695 PB - Wiley-Liss CY - New York ER -