@misc{SiekerDuwePothetal.2012, author = {Sieker, T. and Duwe, A. and Poth, S. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Itacons{\"a}ureherstellung aus Buchenholz-Hydrolysaten}, series = {Chemie Ingenieur Technik}, volume = {84}, journal = {Chemie Ingenieur Technik}, number = {8}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201250414}, pages = {1300}, year = {2012}, abstract = {Aus h{\"o}lzernen Cellulosen und Hemicellulosen k{\"o}nnen durch enzymatische Hydrolyse fermentierbare Zucker f{\"u}r die Herstellung von Chemikalien und Treibstoffen gewonnen werden. Die bisherige Forschung fokussiert sich oft auf die Nutzung dieser Zucker zur Gewinnung von Ethanol. Daneben muss aber auch die stoffliche Nutzung zur Gewinnung von Grundchemikalien ber{\"u}cksichtigt werden. Eine solche Grundchemikalie ist Itakons{\"a}ure. Obwohl die biotechnologische Itacons{\"a}ureproduktion bereits eingehend untersucht und etabliert ist, gestaltet sie sich im Rahmen von Bioraffinerien der zweiten Generation als schwierig, da der {\"u}berwiegend verwendete Produktionsorganismus gegen eine weite Bandbreite von Inhibitoren sensibel ist. Die Herstellung von Itacons{\"a}ure aus Buchenholzhydrolysaten wird im Rahmen der deutschen Lignocellulose-Bioraffinerie entwickelt. Die unbehandelten Hydrolysate erm{\"o}glichen weder das Wachstum von Aspergillus terreus noch die Bildung von Itacons{\"a}ure. Daher werden M{\"o}glichkeiten zur Konditionierung des Hydrolysates mit dem Ziel einer Itacons{\"a}ureproduktion mit hohen Ausbeuten und Konzentrationen vorgestellt.}, language = {de} } @book{Waehlisch2012, author = {W{\"a}hlisch, Georg}, title = {Technisches Zeichnen : L{\"o}sungsvorschl{\"a}ge f{\"u}r das Selbststudium. (Berichte aus dem Maschinenbau)}, publisher = {Shaker}, address = {Aachen}, isbn = {978-3-8440-1159-3}, pages = {[138] S. : zahlr. Ill., graph. Darst.}, year = {2012}, language = {de} } @article{OertelBung2012, author = {Oertel, Mario and Bung, Daniel Bernhard}, title = {Initial stage of two-dimensional dam-break waves: laboratory versus VOF}, series = {Journal of hydraulic research}, volume = {50}, journal = {Journal of hydraulic research}, number = {1}, publisher = {Taylor \& Francis}, address = {London}, issn = {1814-2079 (E-Journal); 0022-1686 (Print)}, doi = {10.1080/00221686.2011.639981}, pages = {89 -- 97}, year = {2012}, abstract = {Since several decades, dam-break waves have been of main research interest. Mathematical approaches have been developed by analytical, physical and numerical models within the past 120 years. During the past 10 years, the number of research investigations has increased due to improved measurement techniques as well as significantly increased computer memories and performances. In this context, the present research deals with the initial stage of two-dimensional dam-break waves by comparing physical and numerical model results as well as analytical approaches. High-speed images and resulting particle image velocimetry calculations are thereby compared with the numerical volume-of-fluid (VOF) method, included in the commercial code FLOW-3D. Wave profiles and drag forces on placed obstacles are analysed in detail. Generally, a good agreement between the laboratory and VOF results is found.}, language = {en} } @misc{SiekerTippkoetterMuffleretal.2012, author = {Sieker, T. and Tippk{\"o}tter, Nils and Muffler, K. and Ulber, Roland}, title = {Herstellung von Ethanol, Phenols{\"a}uren, organischen S{\"a}uren und Biogas durch vollst{\"a}ndige Nutzung von Grassilage in einer Bioraffinerie}, series = {Chemie Ingenieur Technik}, volume = {84}, journal = {Chemie Ingenieur Technik}, number = {8}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201250415}, pages = {1297}, year = {2012}, abstract = {Gr{\"a}ser sind in der Lage, einen großen Teil der f{\"u}r eine biobasierte Wirtschaft ben{\"o}tigten Biomasse zur Verf{\"u}gung zustellen. Um eine ganzj{\"a}hrige Nutzung des Grases zu gew{\"a}hrleisten, muss eine stabile Lagerung des Grases erreicht werden, was z. B. durch Silieren m{\"o}glich ist. Die konservierende Wirkung der Silierung beruht auf der Bildung organischer S{\"a}uren. Um diese zu gewinnen, wird die Silage gepresst, die organischen S{\"a}uren {\"u}ber Fl{\"u}ssig/Fl{\"u}ssig-Extraktion aus dem Presssaft abgetrenntund mittels chromatographischer Methoden weiter aufgereinigt. Im pr{\"a}sentierten Konzept werden die im Presskuchen enthaltenen Lignocellulosen hydrolysiert und die erhaltenen Monosaccharide zu Ethanol fermentiert. Die Phenols{\"a}uren, die in Gr{\"a}sern die Rolle des Lignins {\"u}bernehmen, k{\"o}nnen simultan mit der Hydrolyse der Polysaccharide enzymatisch abgetrennt und als Nebenprodukt gewonnen werden. Die nach der Abtrennung des Ethanols verbleibenden Fermentationsreststoffe werden f{\"u}r die Herstellung von Biogas verwendet.}, language = {de} } @inproceedings{BeckerEggertFleischeretal.2012, author = {Becker, J{\"o}rg and Eggert, Mathias and Fleischer, Stefan and Heddier, Marcel and Knackstedt, Ralf}, title = {Data Warehouse Design and Legal Visualization - The Applicability of H2 for Reporting}, series = {Proceedings of the 23rd Australasian Conference on Information Systems 2012}, booktitle = {Proceedings of the 23rd Australasian Conference on Information Systems 2012}, pages = {11 S.}, year = {2012}, language = {de} } @article{NguyenDuongTranetal.2012, author = {Nguyen, Nhu Huynh and Duong, Minh Tuan and Tran, Thanh Ngoc and Pham, Phu Tinh and Grottke, O. and Tolba, R. and Staat, Manfred}, title = {Influence of a freeze-thaw cycle on the stress-stretch curves of tissues of porcine abdominal organs}, series = {Journal of Biomechanics}, volume = {45}, journal = {Journal of Biomechanics}, number = {14}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2380}, doi = {10.1016/j.jbiomech.2012.07.008}, pages = {2382 -- 2386}, year = {2012}, abstract = {The paper investigates both fresh porcine spleen and liver and the possible decomposition of these organs under a freeze-thaw cycle. The effect of tissue preservation condition is an important factor which should be taken into account for protracted biomechanical tests. In this work, tension tests were conducted for a large number of tissue specimens from twenty pigs divided into two groups of 10. Concretely, the first group was tested in fresh state; the other one was tested after a freeze-thaw cycle which simulates the conservation conditions before biomechanical experiments. A modified Fung model for isotropic behavior was adopted for the curve fitting of each kind of tissues. Experimental results show strong effects of the realistic freeze-thaw cycle on the capsule of elastin-rich spleen but negligible effects on the liver which virtually contains no elastin. This different behavior could be explained by the autolysis of elastin by elastolytic enzymes during the warmer period after thawing. Realistic biomechanical properties of elastin-rich organs can only be expected if really fresh tissue is tested. The observations are supported by tests of intestines.}, language = {en} } @article{StaatTrenzLohmannetal.2012, author = {Staat, Manfred and Trenz, Eva and Lohmann, Philipp and Frotscher, Ralf and Klinge, Uwe and Tabaza, Ruth and Kirschner-Hermanns, Ruth}, title = {New measurements to compare soft tissue anchoring systems in pelvic floor surgery}, series = {Journal of Biomedical Materials Research Part B: Applied Biomaterials}, volume = {100B}, journal = {Journal of Biomedical Materials Research Part B: Applied Biomaterials}, number = {4}, publisher = {Wiley}, address = {Hoboken, NJ}, issn = {1552-4981}, doi = {10.1002/jbm.b.32654}, pages = {924 -- 933}, year = {2012}, abstract = {Suburethral slings as well as different meshes are widely used treating stress urinary incontinence and prolaps in women. With the development of MiniSlings and special meshes using less alloplastic material anchorage systems become more important to keep devices in place and to put some tension especially on the MiniSlings. To date, there are many different systems of MiniSlings of different companies on the market which differ in the structure of the used meshes and anchors. A new objective measurement method to compare different properties of MiniSling systems (mesh and anchor) is presented in this article. Ballistic gelatine acts as soft tissue surrogate. Significant differences in parameters like pull-out strength of anchors or shrinkage of meshes under loading conditions have been determined. The form and size of the anchors as well as the structural stability of the meshes are decisive for a proper integration. The tested anchorings sytems showed markedly different mechanical function at their respective load bearing capacity. As the stable fixation of the device in tissue is a prerequisite for a permanet reinforcement, the proposed test system permits further optimisation of anchor and mesh devices to improve the success of the surgical treatment}, language = {en} } @article{NovacekTranKlingeetal.2012, author = {Novacek, V. and Tran, Thanh Ngoc and Klinge, U. and Tolba, R. H. and Staat, Manfred and Bronson, D. G. and Miesse, A. M. and Whiffen, J. and Turquier, F.}, title = {Finite element modelling of stapled colorectal end-to-end anastomosis : Advantages of variable height stapler design}, series = {Journal of Biomechanics}, volume = {45}, journal = {Journal of Biomechanics}, number = {115}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-2380}, doi = {10.1016/j.jbiomech.2012.07.021}, pages = {2693 -- 2697}, year = {2012}, abstract = {The impact of surgical staplers on tissues has been studied mostly in an empirical manner. In this paper, finite element method was used to clarify the mechanics of tissue stapling and associated phenomena. Various stapling modalities and several designs of circular staplers were investigated to evaluate the impact of the device on tissues and mechanical performance of the end-to-end colorectal anastomosis. Numerical simulations demonstrated that a single row of staples is not adequate to resist leakage due to non-linear buckling and opening of the tissue layers between two adjacent staples. Compared to the single staple row configuration, significant increase in stress experienced by the tissue at the inner staple rows was observed in two and three rows designs. On the other hand, adding second and/or third staple row had no effect on strain in the tissue inside the staples. Variable height design with higher staples in outer rows significantly reduced the stresses and strains in outer rows when compared to the same configuration with flat cartridge.}, language = {en} } @article{VerbanellaFabo2012, author = {Verbanella, Stresa and Fabo, Sabine}, title = {Mit Pinsel und Farbe hacken : Interview mit Sabine Fabo}, series = {Remotewords.net}, journal = {Remotewords.net}, year = {2012}, abstract = {Remotewords makes its mark on the picturesque "Bar Verbanella", located in Stresa near Isola Bella on Lago Maggiore. The words CUM GRANO SALIS (with a grain of salt) by Sabine Fabo, art theorist on media contexts, were applied to its roof in collaboration with the German-Italian art organization "Lo spirito del Lago".}, language = {de} } @article{BassamHeschelerTemizArtmannetal.2012, author = {Bassam, Rasha and Hescheler, J{\"u}rgen and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard and Digel, Ilya}, title = {Effects of spermine NONOate and ATP on the thermal stability of hemoglobin}, series = {BMC Biophysics}, volume = {5}, journal = {BMC Biophysics}, publisher = {BioMed Central}, address = {London}, issn = {2046-1682}, doi = {10.1186/2046-1682-5-16}, pages = {Art. 16}, year = {2012}, abstract = {Background Minor changes in protein structure induced by small organic and inorganic molecules can result in significant metabolic effects. The effects can be even more profound if the molecular players are chemically active and present in the cell in considerable amounts. The aim of our study was to investigate effects of a nitric oxide donor (spermine NONOate), ATP and sodium/potassium environment on the dynamics of thermal unfolding of human hemoglobin (Hb). The effect of these molecules was examined by means of circular dichroism spectrometry (CD) in the temperature range between 25°C and 70°C. The alpha-helical content of buffered hemoglobin samples (0.1 mg/ml) was estimated via ellipticity change measurements at a heating rate of 1°C/min. Results Major results were: 1) spermine NONOate persistently decreased the hemoglobin unfolding temperature T u irrespectively of the Na + /K + environment, 2) ATP instead increased the unfolding temperature by 3°C in both sodium-based and potassium-based buffers and 3) mutual effects of ATP and NO were strongly influenced by particular buffer ionic compositions. Moreover, the presence of potassium facilitated a partial unfolding of alpha-helical structures even at room temperature. Conclusion The obtained data might shed more light on molecular mechanisms and biophysics involved in the regulation of protein activity by small solutes in the cell.}, language = {en} } @incollection{NiendorfWinterFrauenrath2012, author = {Niendorf, Thoralf and Winter, Lukas and Frauenrath, Tobias}, title = {Electrocardiogram in an MRI environment: Clinical needs, practical considerations, safety implications, technical solutions and fFuture directions}, series = {Advances in Electrocardiograms - Methods and Analysis}, booktitle = {Advances in Electrocardiograms - Methods and Analysis}, editor = {Millis, Richard}, publisher = {IntechOpen}, address = {London}, isbn = {978-953-307-923-3 (print)}, doi = {10.5772/24340}, pages = {309 -- 324}, year = {2012}, language = {en} } @article{MansurovDigelBiisenbaevetal.2012, author = {Mansurov, Z. and Digel, Ilya and Biisenbaev, M. and Savistkaya, I. and Kistaubaeva, A. and Akimbekov, Nuraly S. and Zhubanova, A.}, title = {Bio-composite material on the basis of carbonized rice husk in biomedicine and environmental applications}, series = {Eurasian Chemico-Technological Journal}, volume = {14}, journal = {Eurasian Chemico-Technological Journal}, number = {2}, publisher = {Institute of Combustion Problems}, address = {Almaty}, issn = {2522-4867}, doi = {10.18321/ectj105}, pages = {115 -- 131}, year = {2012}, language = {en} } @article{FrauenrathFuchsDieringeretal.2012, author = {Frauenrath, Tobias and Fuchs, Katharina and Dieringer, Matthias A. and {\"O}zerdem, Celal and Patel, Nishan and Renz, Wolfgang and Greiser, Andreas and Elgeti, Thomas and Niendorf, Thoralf}, title = {Detailing the use of magnetohydrodynamic effects for synchronization of MRI with the cardiac cycle: A feasibility study}, series = {Journal of Magnetic Resonance Imaging}, volume = {36}, journal = {Journal of Magnetic Resonance Imaging}, number = {2}, publisher = {Wiley-Liss}, address = {New York}, issn = {1522-2586}, doi = {10.1002/jmri.23634}, pages = {364 -- 372}, year = {2012}, abstract = {Purpose: To investigate the feasibility of using magnetohydrodynamic (MHD) effects for synchronization of magnetic resonance imaging (MRI) with the cardiac cycle. Materials and Methods: The MHD effect was scrutinized using a pulsatile flow phantom at B0 = 7.0 T. MHD effects were examined in vivo in healthy volunteers (n = 10) for B0 ranging from 0.05-7.0 T. Noncontrast-enhanced MR angiography (MRA) of the carotids was performed using a gated steady-state free-precession (SSFP) imaging technique in conjunction with electrocardiogram (ECG) and MHD synchronization. Results: The MHD potential correlates with flow velocities derived from phase contrast MRI. MHD voltages depend on the orientation between B0 and the flow of a conductive fluid. An increase in the interelectrode spacing along the flow increases the MHD potential. In vivo measurement of the MHD effect provides peak voltages of 1.5 mV for surface areas close to the common carotid artery at B0 = 7.0 T. Synchronization of MRI with the cardiac cycle using MHD triggering is feasible. MHD triggered MRA of the carotids at 3.0 T showed an overall image quality and richness of anatomic detail, which is comparable to ECG-triggered MRAs. Conclusion: This feasibility study demonstrates the use of MHD effects for synchronization of MR acquisitions with the cardiac cycle. J. Magn. Reson. Imaging 2012;36:364-372. © 2012 Wiley Periodicals, Inc.}, language = {en} } @misc{TippkoetterPasteurMeyeretal.2012, author = {Tippk{\"o}tter, Nils and Pasteur, A. and Meyer, C. and Kampeis, P. and Diller, R. and Ulber, Roland}, title = {Aufreinigung von Cephalosporin C durch por{\"o}se, selektiv-beschichtete Magnetpartikel}, series = {Chemie Ingenieur Technik}, volume = {84}, journal = {Chemie Ingenieur Technik}, number = {8}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201250391}, pages = {1369 -- 1370}, year = {2012}, abstract = {Die selektive Isolierung von Cephalosporin C (CPC) aus komplexen Fermentationssuspensionen unter Einsatz magnetischer Separation ist das Ziel dieser Arbeit. Das Verfahren wird im fr{\"u}hen Stadium der Aufarbeitung genutzt, um CPC zu stabilisieren und somit die Produktausbeute zu erh{\"o}hen. Als Adsorbersysteme f{\"u}r CPC wurden neben einem projektinternen magnetischen Material ND 10322, dessen Oberfl{\"a}chenladungen spezifisch f{\"u}r die Bindung des Zielmolek{\"u}ls synthetisiert wurden, verschiedene kommerzielle Partikelsysteme verglichen. Es konnten massenspezifische Maximalbeladungen von 51 mg g⁻¹ erreicht werden. Weiterhin wurde die Stabilit{\"a}t von CPC untersucht. Unter optimalen Adsorptionsbedingungen kann CPC stabilisiert werden, so dass die Geschwindigkeitskonstante der Degradation des b-Lactam-Rings unter diesen Bedingungen unter 0,005 h⁻¹ liegt. Untersuchungen zur Wiederverwertbarkeit der neuen Adsorbers zeigten eine irreversible Bindung geringer CPC-Mengen nach dem ersten Einsatz. Nach zw{\"o}lf Zyklen tritt eine irreversible Bindung von CPC ein, was zu einer signifikanten Reduktion der Adsorptionsf{\"a}higkeit f{\"u}hrt. Die Anh{\"a}ufung des CPC auf dem Adsorber konnte durch IR-Untersuchungen auf die Bildung einer Peptidbindung zwischen Carboxylgruppen des CPC und Aminogruppe der Adsorberoberfl{\"a}che zur{\"u}ckgef{\"u}hrt werden.}, language = {de} } @article{GorissenStaatLaack2012, author = {Gorissen, P. and Staat, Manfred and Laack, Walter van}, title = {Experimentelle Kraftmessungen als Beitrag zur Wirksamkeitsbeurteilung von Schienbeinschonern im Fußballsport}, series = {OUP Zeitschrift f{\"u}r die orthop{\"a}dische und unfallchirurgische Praxis}, volume = {1}, journal = {OUP Zeitschrift f{\"u}r die orthop{\"a}dische und unfallchirurgische Praxis}, number = {1}, publisher = {Deutscher {\"A}rzte-Verlag}, address = {K{\"o}ln}, issn = {2193-5785}, doi = {10.3238/oup.2012.0010-0015}, pages = {10 -- 15}, year = {2012}, abstract = {Diese Studie besch{\"a}ftigte sich mit der D{\"a}mpfungswirkung von Schienbeinschonern, wie sie beim Fußball zum Einsatz kommen. Sie wurde mit Hilfe eines Pendelhammers durchgef{\"u}hrt, der verschiedene Aufschlagkr{\"a}fte auf die Schoner erm{\"o}glichte. Dabei wurde deutlich, dass Schienbeinschoner die beste Wirkung bei Maximalkr{\"a}ften unterhalb von 5kN erreichen k{\"o}nnen, dass bei gr{\"o}ßerer Belastung allerdings Verbesserungsbedarf besteht. Hierf{\"u}r konnte, u.a. durch den Einsatz neuer Materialien, ein guter Ansatzpunkt im „ad{\"a}quaten Zusammenspiel von Schale und Polsterung" der Schoner gefunden werden. Die Untersuchung hat weiterhin gezeigt, dass zumindest teilweise eine deutliche Verbesserung der D{\"a}mpfungswirkung der Schienbeinschoner in den letzten Jahren erreicht werden konnte.}, subject = {Fußball}, language = {de} } @inproceedings{FerreinKallweitLautermann2012, author = {Ferrein, Alexander and Kallweit, Stephan and Lautermann, Mark}, title = {Towards an autonomous pilot system for a tunnel boring machine}, series = {5th Robotics and Mechatronics Conference of South Africa (ROBMECH) : 26 - 27 November 2012 ; CSIR International Conference Centre Gauteng South Africa}, booktitle = {5th Robotics and Mechatronics Conference of South Africa (ROBMECH) : 26 - 27 November 2012 ; CSIR International Conference Centre Gauteng South Africa}, publisher = {IEEE}, address = {Piscataway, NJ}, isbn = {978-1-4673-5183-6}, year = {2012}, language = {en} } @misc{FrauenrathFuchsHezeletal.2012, author = {Frauenrath, Tobias and Fuchs, Katharina and Hezel, Fabian and Dieringer, Matthias A. and Rieger, Jan and Niendorf, Thoralf}, title = {Improved cardiac triggering by combining multiple physiological signals: a cardiac MR feasibility study at 7.0 T}, series = {2012 ISMRM Annual Meeting Proceedings}, journal = {2012 ISMRM Annual Meeting Proceedings}, issn = {1545-4428}, year = {2012}, abstract = {In current clinical cardiovascular MR (CMR) practice cardiac motion is commonly dealt with using ECG based synchronization. However, ECG is corrupted by magneto-hydrodynamic (MHD) effects in magnetic fields. This leads to artifacts in the ECG trace and evokes severe T-wave elevations, which might be misinterpreted as R-waves resulting in erroneous triggering. At (ultra)high field strengths, the propensity of ECG recordings to MHD effects is further pronounced. Pulse oximetry (POX) being inherently sensitive to blood oxygenation provides an alternative approach for cardiac gating. However, due to the travel time of the blood the peak of maximum oxygenation and hence the trigger is delayed by approx. 300 ms with respect to the ECG's R-wave. Also the peak of maximum oxygenation shows a jitter of up to 65 ms. Alternative triggering approaches include acoustic cardiac triggering (ACT). In current clinical practice cardiac gating / triggering commonly relies on using single physiological signals only. Realizing this limitation this study proposes a combined triggering approach which exploits multiple physiological signals including ECG, POX or ACT to track cardiac activity. The feasibility of the coupled approach is examined for LV function assessment at 7.0 T. For this purpose, breath-held 2D-CINE imaging in conjunction with cardiac synchronization was performed paralleled by real time logging of physiological waveforms to track (mis)synchronization between the cardiac cycle and data acquisition. Combinations of the ECG, POX and ACT signals were evaluated and processed in real time to facilitate reliable trigger information.}, language = {en} } @article{Wilke2012, author = {Wilke, Thomas}, title = {Architekturzeichnung als Instrument der Theoriebildung. Lineamenta vs. Portraicture - Architekturdarstellung zwischen Wissenschaft und {\"O}ffentlichkeit. Tagung des DFG-Netzwerks-Schnittstelle Bild in Zusammenarbeit mit dem Lehrstuhl f{\"u}r Kunstgeschichte der Universit{\"a}t Regensburg, 28.4.2012.}, series = {Kunstchronik}, volume = {65}, journal = {Kunstchronik}, number = {9/10}, publisher = {Fachverlag Hans Carl}, address = {N{\"u}rnberg}, issn = {0023-5474}, pages = {494 -- 499}, year = {2012}, language = {de} } @article{ScheerBalimaneHaywardetal.2012, author = {Scheer, Nico and Balimane, Praveen and Hayward, Michael D. and Buechel, Sandra and Kauselmann, Gunther and Wolf, C. Roland}, title = {Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line}, series = {Drug Metabolism and Disposition}, volume = {40}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/dmd.112.047605}, pages = {2212 -- 2218}, year = {2012}, abstract = {The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(-/-)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(-/-) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2.}, language = {en} } @article{ScheerKapelyukhRodeetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland}, title = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines}, series = {Molecular Pharmacology}, volume = {82}, journal = {Molecular Pharmacology}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.112.080036}, pages = {1022 -- 1029}, year = {2012}, abstract = {Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction.}, language = {en} }