TY - JOUR A1 - Riedel, Marc A1 - Kartchemnik, Julia A1 - Schöning, Michael Josef A1 - Lisdat, Fred T1 - Impedimetric DNA detection – steps forward to sensorial application JF - Analytical chemistry N2 - This study describes a label-free impedimetric sensor based on short ssDNA recognition elements for the detection of hybridization events. We concentrate on the elucidation of the influence of target length and recognition sequence position on the sensorial performance. The impedimetric measurements are performed in the presence of the redox system ferri-/ferrocyanide and show an increase in charge transfer resistance upon hybridization of ssDNA to the sensor surface. Investigations on the impedimetric signal stability demonstrate a clear influence of the buffers used during the sensor preparation and the choice of the passivating mercaptoalcanol compound. A stable sensor system has been developed, enabling a reproducible detection of 25mer target DNA in the low nanomolar range. After hybridization, a sensor regeneration can be reached with deionized water by adjustment of effective convection conditions, ensuring a sensor reusability. By investigations of longer targets with overhangs exposed to the solution, we can demonstrate applicability of the impedimetric detection for longer ssDNA. However, a decreasing charge transfer resistance change (ΔRct) is found by extending the overhang. As a strategy to increase the impedance change for longer target strands, the position of the recognition sequence can be designed in a way that a small overhang is exposed to the electrode surface. This is found to result in an increase in the relative Rct change. These results suggest that DNA and consequently negative charge near the electrode possess a larger impact on the impedimetric signal than DNA further away. Y1 - 2014 U6 - http://dx.doi.org/10.1021/ac501800q SN - 1520-6882 (E-Journal); 0003-2700 (Print); 0096-4484 (Print) VL - 86 (2014) IS - 15 SP - 7867 EP - 7874 PB - ACS Publications CY - Columbus ER - TY - CHAP A1 - Ritz, Thomas A1 - Izquierdo Tello, César A1 - Damm, Sebastian T1 - Connecting a pedelec to the cloud as basis for gamification in multi modal mobility planning T2 - MobileCloud 2014 : 2nd IEEE International Conference on Mobile Cloud Computing, Services, and Engineering Oxford, United Kingdom 7-10 April 2014 Y1 - 2014 SN - 978-1-4799-2504-9 U6 - http://dx.doi.org/10.1109/MobileCloud.2014.25 SP - 101 EP - 108 PB - IEEE Service Center CY - Piscataway, NJ ER - TY - CHAP A1 - Rosin, Julia A1 - Butenweg, Christoph T1 - Seismic isolation of cylindrical liquid storage tanks T2 - Proceedings of the 9th European Conference on Structural Dynamics, EURODYN 2014 Porto, Portugal, 30 June - 2 July 2014 / A. Cunha, E. Caetano, .... (eds.) Y1 - 2014 SN - 978-972-752-165-4 SP - 3145 EP - 3152 CY - Porto ER - TY - CHAP A1 - Rosin, Julia A1 - Henneböhl, Benedickt A1 - Butenweg, Christoph T1 - Global buckling analysis of cylindrical liquid storage tanks under earthquake loading T2 - 2nd European Conference on Earthquake Engineering and Seismology 2014 (2nd ECEES) : joint event of the 15th European Conference on Earthquake Engineering and the 34th General Assembly of the European Seismological Commission : Istanbul, Turkey, 25-29 August 2014 / European Association for Earthquake Engineering (EAEE) ; Vol. 6 Y1 - 2014 SN - 978-1-5108-1021-1 SP - 5270 EP - 5281 PB - Curran Associates, Inc. CY - Red Hook, NY ER - TY - CHAP A1 - Rosin, Julia A1 - Kubalski, Thomas A1 - Butenweg, Christoph T1 - Seismic Design of cylindrical liquid storage tanks T2 - Seismic design of industrial facilities : proceedings of the International Conference on Seismic Design of Industrial Facilities (SeDIF-Conference) ; [Aachen, 26. - 27. September 2013] / Chair of Structural Statics and Dynamics, RWTH Aachen. Sven Klinkel ..., ed. Y1 - 2014 SN - 978-3-658-02810-7 (E-Book) ; 978-3-658-02809-1 (Print) U6 - http://dx.doi.org/10.1007/978-3-658-02810-7_36 SP - 429 EP - 440 PB - Springer Vieweg CY - Wiesbaden ER - TY - CHAP A1 - Rousseau, Alain A1 - Kern, Alexander T1 - How to deal with environmental risk in IEC 62305-2 T2 - 2014 International Conference on Lightning Protection (ICLP), Shanghai, China N2 - The 2nd edition of the lightning risk management standard (IEC 62305-2) considers structures, which may endanger environment. In these cases, the loss is not limited to the structure itself, which is valid for usual structures. In the past (Edition 1) this danger was simply taken into account by a special hazard factor, multiplying the existing risk for the structure with a number. Now, in the edition 2, we add to the risk for the structure itself a “second risk” due to the losses outside the structure. The losses outside can be treated independently from what occurs inside. This is a major advantage to analyze the risk for sensitive structures, like chemical plants, nuclear plants, or structures containing explosives, etc. In this paper, the existing procedure given by the European version EN 62305-2 Ed.2 is further developed and applied to a few structures. Y1 - 2014 SP - 521 EP - 527 ER - TY - JOUR A1 - Salpati, Laurent A1 - Chu, Xiaoyan A1 - Chen, Liangfu A1 - Prasad, Bhagwat A1 - Dallas, Shannon A1 - Evers, Raymond A1 - Mamaril-Fishman, Donna A1 - Geier, Ethan G. A1 - Kehler, Jonathan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Soars, Matthew G. A1 - Unadkat, Jashvant D. A1 - van Waterschoot, Robert A.B. A1 - Yabut, Jocelyn A1 - Schinkel, Alfred H. A1 - Scheer, Nico A1 - Rode, Anja T1 - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins JF - Drug Metabolism and Disposition N2 - Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Sawada, Kazuaki A1 - Nakazawa, Hirokazu A1 - Takenaga, Shoko A1 - Hizawa, Takeshi A1 - Futagawa, Masato A1 - Dasai, Fumihiro A1 - Sakurai, Takashi A1 - Okumura, Koichi A1 - Hattori, Toshiaki A1 - Ishida, Makoto T1 - Multimodal bioimage sensor JF - IEICE transactions on fundamentals of electronics, communidations and computer sciences N2 - To visualize the biochemical distribution two-dimensionally, we invented a solid-state-type ion image sensor that indicates the chemical activity of solutions and cells. The device, which consists of a CCD array covered with a functionalized membrane to detect charge accumulation, is highly sensitive to changes in the concentration and two-dimensional distribution of ions and biomaterials. Y1 - 2014 U6 - http://dx.doi.org/10.1587/transfun.E97.A.726 SN - 0916-8508 (Print) ; 1745-1337 (Online) VL - E97-A (2014) IS - 3 SP - 726 EP - 733 PB - IEICE CY - Tokyo 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 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - http://dx.doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER -