@article{ScheerKapelyukhMcEwanetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and McEwan, Jillian and Beuger, Vincent and Stanley, Lesley A. and Rode, Anja and Wolf, C. Roland}, title = {Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines}, series = {Molecular Pharmacology}, volume = {81}, journal = {Molecular Pharmacology}, number = {1}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.075192}, pages = {63 -- 72}, year = {2012}, abstract = {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.}, language = {en} } @inproceedings{BitzKraffOrzadaetal.2012, author = {Bitz, Andreas and Kraff, O. and Orzada, S. and Maderwald, S. and Brote, I. and Johst, S. and Ladd, E.}, title = {Assessment of RF Safety of Transmit Coils at 7 Tesla by Experimental and Numerical Procedures (490.)}, series = {19th annual ISMRM scientific meeting and exhibition 2011 : Montreal, Quebec, Canada, 7 - 13 May 2011}, booktitle = {19th annual ISMRM scientific meeting and exhibition 2011 : Montreal, Quebec, Canada, 7 - 13 May 2011}, number = {Volume 1}, publisher = {Curran}, address = {Red Hook, NY}, isbn = {978-1-61839-284-8}, pages = {475}, year = {2012}, language = {en} } @article{PaulssenKongArciszewskietal.2012, author = {Paulßen, Elisabeth and Kong, Shushu and Arciszewski, Pawel and Wielbalck, Swantje and Abram, Ulrich}, title = {Aryl and NHC Compounds of Technetium and Rhenium}, series = {Journal of the American Chemical Society}, volume = {134}, journal = {Journal of the American Chemical Society}, number = {22}, publisher = {ACS Publications}, address = {Washington, DC}, issn = {1520-5126}, doi = {10.1021/ja3033718}, pages = {9118 -- 9121}, year = {2012}, abstract = {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.}, language = {en} } @article{PaulssenNgyugenKahlckeetal.2012, author = {Paulßen, Elisabeth and Ngyugen, Hung Huy and Kahlcke, Nils and Deflon, Victor M. and Abram, Ulrich}, title = {Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines}, series = {Polyhedron}, volume = {40}, journal = {Polyhedron}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0277-5387}, doi = {10.1016/j.poly.2012.04.008}, pages = {153 -- 158}, year = {2012}, abstract = {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.}, language = {en} } @phdthesis{Oflaz2012, author = {Oflaz, Hakan}, title = {Entwicklung eines Prototypen zur Prognose von Fr{\"u}hgeburten : ein biomedizintechnischer Ansatz}, publisher = {Deutsche Zentralbibliothek f{\"u}r Medizin}, address = {K{\"o}ln}, doi = {10.4126/38m-004639208}, year = {2012}, language = {en} } @phdthesis{KurulganDemirci2012, author = {Kurulgan Demirci, Eylem}, title = {The effect of rhAPC on contractile tension : an in-vitro sepsis model of cardiomyocytes and endothelial cells}, year = {2012}, language = {en} } @article{CzarneckiSpiliopoulou2012, author = {Czarnecki, Christian and Spiliopoulou, Myra}, title = {A holistic framework for the implementation of a next generation network}, series = {International Journal of Business Information Systems}, volume = {9}, journal = {International Journal of Business Information Systems}, number = {4}, publisher = {Inderscience Enterprises}, address = {Olney, Bucks}, issn = {1746-0972}, doi = {10.1504/IJBIS.2012.046291}, pages = {385 -- 401}, year = {2012}, abstract = {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.}, language = {en} } @book{Gell2012, author = {Gell, Sebastian}, title = {Determinants of earnings forecast error, earnings forecast revision and earnings forecast accuracy}, publisher = {Springer Gabler}, address = {Wiesbaden}, isbn = {978-3-8349-3936-4}, doi = {10.1007/978-3-8349-3937-1}, pages = {XXIV, 125 Seiten}, year = {2012}, abstract = {​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?}, language = {en} } @article{OrzadaMaderwaldPoseretal.2012, author = {Orzada, S. and Maderwald, S. and Poser, B. A. and Johst, S. and Kannengiesser, S. and Ladd, M. E. and Bitz, Andreas}, title = {Time-interleaved acquisition of modes: an analysis of SAR and image contrast implications}, series = {Magnetic Resonance in Medicine}, volume = {67}, journal = {Magnetic Resonance in Medicine}, number = {4}, publisher = {Wiley-Liss}, address = {New York}, issn = {1522-2594}, doi = {10.1002/mrm.23081}, pages = {1033 -- 1041}, year = {2012}, abstract = {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.}, language = {en} } @article{KobusBitzUdenetal.2012, author = {Kobus, Thiele and Bitz, Andreas and Uden, Mark J. van and Lagemaat, Miram W. and Rothgang, Eva and Orzada, Stephan and Heerschap, Arend and Scheenen, Tom W. J.}, title = {In vivo 31P MR spectroscopic imaging of the human prostate at 7 T: safety and feasibility}, series = {Magnetic Resonance in Medicine}, volume = {68}, journal = {Magnetic Resonance in Medicine}, number = {6}, publisher = {Wiley-Liss}, address = {New York}, issn = {1522-2594}, doi = {10.1002/mrm.24175}, pages = {1683 -- 1695}, year = {2012}, abstract = {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.}, language = {en} }