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 - TY - JOUR A1 - Olbertz, Klaus T1 - Gestaltung des Anstellungsvertrags - Der Compliance-Beauftragte JF - Arbeit und Arbeitsrecht : AuA N2 - Ein Compliance-Beauftragter soll dafür Sorge tragen, dass aus dem Unternehmen heraus keine Rechtsverletzungen begangen werden. Aber welche rechtlichen Notwendigkeiten und Möglichkeiten resultieren daraus für die Gestaltung des Anstellungsvertrags? Y1 - 2014 SN - 0323-4568 IS - 7 SP - 400 EP - 403 PB - Huss Medien CY - Berlin ER - TY - JOUR A1 - Feichtinger, Linda M. A1 - Eilmann, Britta A1 - Buchmann, Nina A1 - Rigling, Andreas T1 - Growth adjustments of conifers to drought and to century-long irrigation JF - Forest Ecology and Management N2 - Our knowledge on tree responses to drought is mainly based on short-term manipulation experiments which do not capture any possible long-term adjustments in this response. Therefore, historical water channels in inner-Alpine dry valleys were used as century-long irrigation experiments to investigate adjustments in tree growth to contrasting water supply. This involved quantifying the tree-ring growth of irrigated and non-irrigated (control) Scots pine (Pinus sylvestris L.) in Valais (Switzerland), as well as European larch (Larix decidua Mill.) and black pine (Pinus nigra Arnold) in Vinschgau (Italy). Furthermore, the adjustments in radial growth of Scots pine and European larch to an abrupt stop in irrigation were analyzed. Irrigation promoted the radial growth of all tree species investigated compared to the control: (1) directly through increased soil water availability, and (2) indirectly through increased soil nutrients and humus contents in the irrigated plots. Irrigation led to a full elimination of growth responses to climate for European larch and black pine, but not for Scots pine, which might become more sensitive to drought with increasing tree size in Valais. For the control trees, the response of the latewood increment to water availability in July/August has decreased in recent decades for all species, but increased in May for Scots pine only. The sudden irrigation stop caused a drop in radial growth to a lower level for Scots pine or similar level for larch compared to the control for up to ten years. However, both tree species were then able to adjust to the new conditions and subsequently grew with similar (Scots pine) or even higher growth rates (larch) than the control. To estimate the impact of climate change on future forest development, the duration of manipulation experiments should be on longer time scales in order to capture adjustment processes and feedback mechanisms of forest ecosystems. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.foreco.2014.08.008 SN - 1872-7042 (Online) SN - 0378-1127 (Print) VL - 2014 IS - 334 SP - 96 EP - 105 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Alebouyeh Samami, Behzad A1 - Pieper, Martin A1 - Breitbach, Gerd A1 - Hodapp, Josef T1 - Heat production in the windings of the stators of electric machines under stationary condition JF - Heat and mass transfer N2 - In electric machines due to high currents and resistive losses (joule heating) heat is produced. To avoid damages by overheating the design of effective cooling systems is required. Therefore the knowledge of heat sources and heat transfer processes is necessary. The purpose of this paper is to illustrate a good and effective calculation method for the temperature analysis based on homogenization techniques. These methods have been applied for the stator windings in a slot of an electric machine consisting of copper wires and resin. The key quantity here is an effective thermal conductivity, which characterizes the heterogeneous wire resin-arrangement inside the stator slot. To illustrate the applicability of the method, the analysis of a simplified, homogenized model is compared with the detailed analysis of temperature behavior inside a slot of an electric machine according to the heat generation. We considered here only the stationary situation. The achieved numerical results are accurate and show that the applied homogenization technique works in practice. Finally the results of simulations for the two cases, the original model of the slot and the homogenized model chosen for the slot (unit cell), are compared to experimental results. Y1 - 2014 U6 - http://dx.doi.org/10.1007/s00231-014-1371-8 SN - 0947-7411 (Print) ; 1432-1181 (E-Journal) VL - 50 SP - 1707 EP - 1716 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Heine, A. A1 - Herrmann, G. A1 - Selmer, Thorsten A1 - Terwesten, F. A1 - Buckel, W. A1 - Reuter, K. T1 - High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily JF - Proteins N2 - Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 Å as well as in complex with CoA at a resolution of 1.59 Å. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called “hot dog fold” which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all “hot dog fold” proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041–2053. © 2014 Wiley Periodicals, Inc. Y1 - 2014 U6 - http://dx.doi.org/10.1002/prot.24557 SN - 1097-0134 (E-Journal); 0887-3585 (Print) VL - 82 IS - 9 SP - 2041 EP - 2053 PB - Wiley-Liss CY - New York ER - TY - JOUR A1 - Miyamoto, Ko-ichiro A1 - Itabashi, Akinori A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - High-speed chemical imaging inside a microfluidic channel JF - Sensors and actuators. B: Chemical N2 - In this study, a high-speed chemical imaging system was developed for visualization of the interior of a microfluidic channel. A microfluidic channel was constructed on the sensor surface of the light-addressable potentiometric sensor (LAPS), on which the ion concentrations could be measured in parallel at up to 64 points illuminated by optical fibers. The temporal change of pH distribution inside the microfluidic channel was recorded at a maximum rate of 100 frames per second (fps). The high frame rate allowed visualization of moving interfaces and plugs in the channel even at a flow velocity of 111 mm/s, which suggests the feasibility of plug-based microfluidic devices for flow-injection analysis (FIA). Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.snb.2013.12.090 SN - 1873-3077 (E-Journal); 0925-4005 (Print) VL - 194 SP - 521 EP - 527 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kronhardt, Valentina A1 - Alexopoulos, Spiros A1 - Reißel, Martin A1 - Sattler, Johannes, Christoph A1 - Hoffschmidt, Bernhard A1 - Hänel, Matthias A1 - Doerbeck, Till T1 - High-temperature thermal storage system for solar tower power plants with open-volumetric air receiver simulation and energy balancing of a discretized model JF - Energy procedia N2 - This paper describes the modeling of a high-temperature storage system for an existing solar tower power plant with open volumetric receiver technology, which uses air as heat transfer medium (HTF). The storage system model has been developed in the simulation environment Matlab/Simulink®. The storage type under investigation is a packed bed thermal energy storage system which has the characteristics of a regenerator. Thermal energy can be stored and discharged as required via the HTF air. The air mass flow distribution is controlled by valves, and the mass flow by two blowers. The thermal storage operation strategy has a direct and significant impact on the energetic and economic efficiency of the solar tower power plants. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.egypro.2014.03.094 SN - 1876-6102 (E-Journal) ; 1876-6102 (Print) VL - 49 SP - 870 EP - 877 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schirra, Julian A1 - Watmuff, Jonathan A1 - Bauschat, J.-Michael T1 - Highly non-planar lifting systems: a relative assessment of existing potential-methodologies to accurately estimate the induced drag JF - 32nd AIAA Applied Aerodynamics Conference 2014 : June, 16-20 2014, Atlanta, Ga. Y1 - 2014 SN - 978-1-62410-288-2 U6 - http://dx.doi.org/10.2514/6.2014-2988 SP - Publ. online ER - TY - JOUR A1 - Whitehead, Mark A1 - Öhlschläger, Peter A1 - Almajhdi, Fahad N. A1 - Alloza, Leonor A1 - Marzábal, Pablo A1 - Meyers, Ann E. A1 - Hitzeroth, Inga I. A1 - Rybicki, Edward P. T1 - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice JF - BMC cancer Y1 - 2014 U6 - http://dx.doi.org/10.1186/1471-2407-14-367 SN - 1471-2407 IS - 14:367 SP - 1 EP - 15 PB - BioMed Central CY - London ER - TY - JOUR A1 - Dachwald, Bernd A1 - Mikucki, Jill A1 - Tulaczyk, Slawek A1 - Digel, Ilya A1 - Espe, Clemens A1 - Feldmann, Marco A1 - Francke, Gero A1 - Kowalski, Julia A1 - Xu, Changsheng T1 - IceMole : A maneuverable probe for clean in situ analysis and sampling of subsurface ice and subglacial aquatic ecosystems JF - Annals of Glaciology N2 - There is significant interest in sampling subglacial environments for geobiological studies, but they are difficult to access. Existing ice-drilling technologies make it cumbersome to maintain microbiologically clean access for sample acquisition and environmental stewardship of potentially fragile subglacial aquatic ecosystems. The IceMole is a maneuverable subsurface ice probe for clean in situ analysis and sampling of glacial ice and subglacial materials. The design is based on the novel concept of combining melting and mechanical propulsion. It can change melting direction by differential heating of the melting head and optional side-wall heaters. The first two prototypes were successfully tested between 2010 and 2012 on glaciers in Switzerland and Iceland. They demonstrated downward, horizontal and upward melting, as well as curve driving and dirt layer penetration. A more advanced probe is currently under development as part of the Enceladus Explorer (EnEx) project. It offers systems for obstacle avoidance, target detection, and navigation in ice. For the EnEx-IceMole, we will pay particular attention to clean protocols for the sampling of subglacial materials for biogeochemical analysis. We plan to use this probe for clean access into a unique subglacial aquatic environment at Blood Falls, Antarctica, with return of a subglacial brine sample. KW - Antarctic Glaciology KW - Extraterrestrial Glaciology KW - Glaciological instruments and methods KW - Subclacial exploration KW - Subglacial lakes Y1 - 2014 U6 - http://dx.doi.org/10.3189/2014AoG65A004 SN - 1727-5644 VL - 55 IS - 65 SP - 14 EP - 22 PB - Cambridge University Press CY - Cambridge ER -