TY - JOUR A1 - Fateri, Miranda A1 - Gebhardt, Andreas A1 - Thümmler, Stefan A1 - Thurn, Laura T1 - Experimental investigation on selective laser melting of glass JF - Physics procedia : 8th International Conference on Laser Assisted Net Shape Engineering LANE 2014 Y1 - 2014 U6 - https://doi.org/10.1016/j.phpro.2014.08.118 SN - 1875-3892 (E-Journal); 1875-3884 (Print) VL - 56 (2014) SP - 357 EP - 364 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Srivastava, A. A1 - Lahiri, S. A1 - Maiti, M. A1 - Knolle, F. A1 - Hoyler, Friedrich A1 - Scherer, Ulrich W. A1 - Schnug, E. W. T1 - Study of naturally occurring radioactive material (NORM) in top soil of Punjab State from the North Western part of India JF - Journal of Radioanalytical and Nuclear Chemistry Y1 - 2014 U6 - https://doi.org/0.1007/s10967-014-3450-1 SN - 1588-2780 (E-Journal); 0022-4081 (Print); 0134-0719 (Print); 0236-5731 (Print); 1417-2097 (Print) VL - 2014 IS - 302 SP - 1049 EP - 1052 PB - Springer Nature CY - Basel ER - TY - JOUR A1 - Siqueira, Jose R. A1 - Molinnus, Denise A1 - Beging, Stefan A1 - Schöning, Michael Josef T1 - Incorporating a hybrid urease-carbon nanotubes sensitive nanofilm on capacitive field-effect sensors for urea detection JF - Analytical chemistry N2 - The ideal combination among biomolecules and nanomaterials is the key for reaching biosensing units with high sensitivity. The challenge, however, is to find out a stable and sensitive film architecture that can be incorporated on the sensor’s surface. In this paper, we report on the benefits of incorporating a layer-by-layer (LbL) nanofilm of polyamidoamine (PAMAM) dendrimer and carbon nanotubes (CNTs) on capacitive electrolyte-insulator-semiconductor (EIS) field-effect sensors for detecting urea. Three sensor arrangements were studied in order to investigate the adequate film architecture, involving the LbL film with the enzyme urease: (i) urease immobilized directly onto a bare EIS [EIS-urease] sensor; (ii) urease atop the LbL film over the EIS [EIS-(PAMAM/CNT)-urease] sensor; and (iii) urease sandwiched between the LbL film and another CNT layer [EIS-(PAMAM/CNT)-urease-CNT]. The surface morphology of all three urea-based EIS biosensors was investigated by atomic force microscopy (AFM), while the biosensing abilities were studied by means of capacitance–voltage (C/V) and dynamic constant-capacitance (ConCap) measureaments at urea concentrations ranging from 0.1 mM to 100 mM. The EIS-urease and EIS-(PAMAM/CNT)-urease sensors showed similar sensitivity (∼18 mV/decade) and a nonregular signal behavior as the urea concentration increased. On the other hand, the EIS-(PAMAM/CNT)-urease-CNT sensor exhibited a superior output signal performance and higher sensitivity of about 33 mV/decade. The presence of the additional CNT layer was decisive to achieve a urea based EIS sensor with enhanced properties. Such sensitive architecture demonstrates that the incorporation of an adequate hybrid enzyme-nanofilm as sensing unit opens new prospects for biosensing applications using the field-effect sensor platform. Y1 - 2014 U6 - https://doi.org/10.1021/ac500458s SN - 1520-6882 (E-Journal); 0003-2700 (Print); 0096-4484 (Print) VL - 86 IS - 11 SP - 5370 EP - 5375 PB - ACS Publications CY - Columbus ER - TY - JOUR A1 - Murib, Mohammed Sharif A1 - Yeap, Weng-Siang A1 - Martens, Daan A1 - Bienstman, Peter A1 - Ceuninck, Ward de A1 - Grinsven, Bart van A1 - Schöning, Michael Josef A1 - Michiels, Luc A1 - Haenen, Ken A1 - Ameloot, Marcel A1 - Serpengüzel, Ali A1 - Wagner, Patrick T1 - Photonic detection and characterization of DNA using sapphire microspheres JF - Journal of biomedical optics N2 - A microcavity-based deoxyribonucleic acid (DNA) optical biosensor is demonstrated for the first time using synthetic sapphire for the optical cavity. Transmitted and elastic scattering intensity at 1510 nm are analyzed from a sapphire microsphere (radius 500  μm, refractive index 1.77) on an optical fiber half coupler. The 0.43 nm angular mode spacing of the resonances correlates well with the optical size of the sapphire sphere. Probe DNA consisting of a 36-mer fragment was covalently immobilized on a sapphire microsphere and hybridized with a 29-mer target DNA. Whispering gallery modes (WGMs) were monitored before the sapphire was functionalized with DNA and after it was functionalized with single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). The shift in WGMs from the surface modification with DNA was measured and correlated well with the estimated thickness of the add-on DNA layer. It is shown that ssDNA is more uniformly oriented on the sapphire surface than dsDNA. In addition, it is shown that functionalization of the sapphire spherical surface with DNA does not affect the quality factor (Q≈104) of the sapphire microspheres. The use of sapphire is especially interesting because this material is chemically resilient, biocompatible, and widely used for medical implants. Y1 - 2014 U6 - https://doi.org/10.1117/1.JBO.19.9.097006 SN - 1560-2281 (E-Journal); 1083-3668 (Print) VL - 19 IS - 9 SP - 097006 PB - SPIE CY - Bellingham ER - TY - JOUR A1 - Handtke, Stefan A1 - Volland, Sonja A1 - Methling, Karen A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Nehls, Jenny A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Liesegang, Heiko A1 - Voigt, Birgit A1 - Daniel, Rolf A1 - Hecker, Michael T1 - Cell physiology of the biotechnological relevant bacterium Bacillus pumilus - An omics-based approach JF - Journal of Biotechnology N2 - Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC–MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed. Y1 - 2014 U6 - https://doi.org/10.1016/j.jbiotec.2014.08.028 SN - 1873-4863 (E-Journal); 0168-1656 (Print) IS - 192(A) SP - 204 EP - 214 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Frotscher, Ralf A1 - Staat, Manfred T1 - Stresses produced by different textile mesh implants in a tissue equivalent JF - BioNanoMaterials N2 - Two single-incision mini-slings used for treating urinary incontinence in women are compared with respect to the stresses they produce in their surrounding tissue. In an earlier paper we experimentally observed that these implants produce considerably different stress distributions in a muscle tissue equivalent. Here we perform 2D finite element analyses to compare the shear stresses and normal stresses in the tissue equivalent for the two meshes and to investigate their failure behavior. The results clearly show that the Gynecare TVT fails for increasing loads in a zipper-like manner because it gradually debonds from the surrounding tissue. Contrary to that, the tissue at the ends of the DynaMesh-SIS direct may rupture but only at higher loads. The simulation results are in good agreement with the experimental observations thus the computational model helps to interpret the experimental results and provides a tool for qualitative evaluation of mesh implants. Y1 - 2014 U6 - https://doi.org/10.1515/bnm-2014-0003 SN - 2191-4672 (E-Journal); 2193-066X (E-Journal); 0011-8656 (Print); 1616-0177 (Print); 2193-0651 (Print) VL - 15 IS - 1-2 SP - 25 EP - 30 PB - De Gruyter CY - Berlin ER - TY - JOUR A1 - Alhwarin, Faraj A1 - Ferrein, Alexander A1 - Scholl, Ingrid T1 - IR stereo kinect: improving depth images by combining structured light with IR stereo Y1 - 2014 SP - 1 EP - 9 ER - TY - JOUR A1 - Guo, Yuanyuan A1 - Miyamoto, Ko-ichiro A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Device simulation of the light-addressable potentiometric sensor for the investigation of the spatial resolution JF - Sensors and actuators B: Chemical N2 - As a semiconductor-based electrochemical sensor, the light-addressable potentiometric sensor (LAPS) can realize two dimensional visualization of (bio-)chemical reactions at the sensor surface addressed by localized illumination. Thanks to this imaging capability, various applications in biochemical and biomedical fields are expected, for which the spatial resolution is critically significant. In this study, therefore, the spatial resolution of the LAPS was investigated in detail based on the device simulation. By calculating the spatiotemporal change of the distributions of electrons and holes inside the semiconductor layer in response to a modulated illumination, the photocurrent response as well as the spatial resolution was obtained as a function of various parameters such as the thickness of the Si substrate, the doping concentration, the wavelength and the intensity of illumination. The simulation results verified that both thinning the semiconductor substrate and increasing the doping concentration could improve the spatial resolution, which were in good agreement with known experimental results and theoretical analysis. More importantly, new findings of interests were also obtained. As for the dependence on the wavelength of illumination, it was found that the known dependence was not always the case. When the Si substrate was thick, a longer wavelength resulted in a higher spatial resolution which was known by experiments. When the Si substrate was thin, however, a longer wavelength of light resulted in a lower spatial resolution. This finding was explained as an effect of raised concentration of carriers, which reduced the thickness of the space charge region. The device simulation was found to be helpful to understand the relationship between the spatial resolution and device parameters, to understand the physics behind it, and to optimize the device structure and measurement conditions for realizing higher performance of chemical imaging systems. Y1 - 2014 U6 - https://doi.org/10.1016/j.snb.2014.08.016 SN - 1873-3077 (E-Journal); 0925-4005 (Print) VL - 204 SP - 659 EP - 665 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Khaydukova, M. M. A1 - Zadorozhnaya, O. A. A1 - Kirsanov, D. O. A1 - Iken, Heiko A1 - Rolka, David A1 - Schöning, Michael Josef A1 - Babain, V. A. A1 - Vlasov, Yu. G. A1 - Legin, A. V. T1 - Multivariate processing of atomic-force microscopy images for detection of the response of plasticized polymeric membranes JF - Russian journal of applied chemistry N2 - The possibility of using the atomic-force microscopy as a method for detection of the analytical signal from plasticized polymeric sensor membranes was analyzed. The surfaces of cadmium-selective membranes based on two polymeric matrices were examined. The digital images were processed with multivariate image analysis techniques. A correlation was found between the surface profile of an ion-selective membrane and the concentration of the ion in solution. Y1 - 2014 U6 - https://doi.org/10.1134/S1070427214030112 SN - 1608-3296 (E-Journal); 1070-4272 (Print) VL - 87 IS - 3 SP - 307 EP - 314 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Holtrup, S. A1 - Sadeghfam, Arash A1 - Heuermann, Holger A1 - Awakowicz, P. T1 - Characterization and optimization technique for microwave-driven high-intensity discharge lamps using hot S-parameters JF - IEEE transactions on microwave theories and techniques N2 - High-intensity discharge lamps can be driven by radio-frequency signals in the ISM frequency band at 2.45 GHz, using a matching network to transform the impedance of the plasma to the source impedance. To achieve an optimal operating condition, a good characterization of the lamp in terms of radio frequency equivalent circuits under operating conditions is necessary, enabling the design of an efficient matching network. This paper presents the characterization technique for such lamps and presents the design of the required matching network. For the characterization, a high-intensity discharge lamp was driven by a monofrequent large signal at 2.45 GHz, whereas a frequency sweep over 300 MHz was performed across this signal to measure so-called small-signal hot S-parameters using a vector network analyzer. These parameters are then used as an equivalent load in a circuit simulator to design an appropriate matching network. Using the measured data as a black-box model in the simulation results in a quick and efficient method to simulate and design efficient matching networks in spite of the complex plasma behavior. Furthermore, photometric analysis of high-intensity discharge lamps are carried out, comparing microwave operation to conventional operation. Y1 - 2014 U6 - https://doi.org/10.1109/TMTT.2014.2342652 SN - 0018-9480 VL - 62 IS - 10 SP - 2471 EP - 2480 PB - IEEE CY - New York ER - TY - JOUR A1 - Müller, Martin A1 - Hirschfeld, Julian A1 - Lambertz, Rita A1 - Schulze Lohoff, Andreas A1 - Lustfeld, Hans A1 - Pfeifer, Heinz A1 - Reißel, Martin T1 - Validation of a novel method for detecting and stabilizing malfunctioning areas in fuel cell stacks JF - Journal of power sources N2 - In this paper a setup for detecting malfunctioning areas of MEAs in fuel cell stacks is described. Malfunctioning areas generate electric cross currents inside bipolar plates. To exploit this we suggest bipolar plates consisting not of two but of three layers. The third one is a highly conducting layer and segmented such that the cross currents move along the segments to the surface of the stack where they can be measured by an inductive sensor. With this information a realistic model can be used to detect the malfunctioning area. Furthermore the third layer will prevent any current inhomogeneity of a malfunctioning cell to spread to neighbouring cells in the stack. In this work the results of measurements in a realistic cell setup will be compared with the results obtained in simulation studies with the same configuration. The basis for the comparison is the reliable characterisation of the electrical properties of the cell components and the implication of these results into the simulation model. The experimental studies will also show the limits in the maximum number of segments, which can be used for a reliable detection of cross currents. Y1 - 2014 U6 - https://doi.org/10.1016/j.jpowsour.2014.08.045 SN - 1873-2755 (E-Journal); 0378-7753 (Print) VL - 272 SP - 225 EP - 232 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Stadler, Alexander Maximilian A1 - Garvey, Christopher J. A1 - Embs, Jan Peter A1 - Koza, Michael Marek A1 - Unruh, Tobias A1 - Artmann, Gerhard A1 - Zaccai, Guiseppe T1 - Picosecond dynamics in haemoglobin from different species: A quasielastic neutron scattering study JF - Biochimica et biophysica acta (BBA): General Subjects Y1 - 2014 U6 - https://doi.org/10.1016/j.bbagen.2014.06.007 SN - 1872-8006 (E-Journal); 0304-4165 (Print) VL - 1840 IS - 10 SP - 2989 EP - 2999 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Malecha, Hartmut A1 - Klubert, J. A1 - Heinen-Fuchs, Sabine T1 - Laserscanning passe? 3-D-Oberflächenmodelle aus Bilddaten und deren messtechnischer Nutzen JF - Wasserwirtschaft Y1 - 2014 SN - 0043-0978 N1 - Die Zeitschrift ist gedruckt in der Bibliothek Bayernallee vorhanden. VL - Jg. 104 IS - Nr. 9 SP - 32 EP - 35 PB - Springer Vieweg CY - Wiesbaden ER - TY - JOUR A1 - Kluczka, Sven A1 - Eckstein, Julian A1 - Alexopoulos, Spiros A1 - Vaeßen, Christiane A1 - Roeb, Martin T1 - Process simulation for solar steam and dry reforming JF - Energy procedia : Proceedings of the SolarPACES 2013 International Conference N2 - In co-operation with the German Aerospace Center, the Solar-Institut Jülich has been analyzing the different technologies that are available for methanol production from CO2 using solar energy. The aim of the project is to extract CO2 from industrial exhaust gases or directly from the atmosphere to recycle it by use of solar energy. Part of the study was the modeling and simulating of a methane reformer for the production of synthesis gas, which can be operated by solar or hybrid heat sources. The reformer has been simplified in such a way that the model is accurate and enables fast calculations. The developed pseudo-homogeneous one- dimensional model can be regarded as a kind of counter-current heat exchanger and is able to incorporate a steam reforming reaction as well as a dry reforming reaction. Y1 - 2014 U6 - https://doi.org/10.1016/j.egypro.2014.03.092 SN - 1876-6102 (E-Journal) VL - 49 SP - 850 EP - 859 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Ratke, Lorenz A1 - Milow, Barbara A1 - Lisinski, Susanne A1 - Hoepfner, Sandra T1 - On an effect of fine ceramic particles on the structure of aerogels JF - Microgravity science and technology Y1 - 2014 U6 - https://doi.org/10.1007/s12217-014-9380-2 SN - 0938-0108 ; 1875-0494 VL - 26 SP - 103 EP - 110 PB - Springer Nature CY - Heidelberg ER - TY - JOUR A1 - Leandro, J. A1 - Bung, Daniel Bernhard A1 - Carvalho, R. T1 - Measuring void fraction and velocity fields of a stepped spillway for skimming flow using non-intrusive methods JF - Experiments in fluids Y1 - 2014 U6 - https://doi.org/10.1007/s00348-014-1732-6 SN - 0723-4864 (Print) ; 1432-1114 (Online) IS - 55 SP - Art. 1732 PB - Springer Nature CY - Heidelberg ER - TY - JOUR A1 - Laack, Walter van T1 - Nahtoderfahrungen aus medizinischer Sicht JF - Deutsche medizinische Wochenschrift : DMW N2 - Nah- versus Nachtoderfahrungen Nahtoderfahrungen (NTE) sind ein Phänomen aus der Kategorie „außergewöhnliche Bewusstseinserfahrungen“. Sie treten in unmittelbarer Nähe des eigenen Todes auf. Oft, aber nicht immer, handelt es sich dabei um Erfahrungen von Personen, die durch ärztliche Maßnahmen wiederbelebt wurden und später davon berichten (NTE-ler). Jedoch kommen solche Phänomene auch bei Menschen vor, die während einer schweren Erkrankung eine lebensbedrohliche Krise haben, hiervon aber spontan genesen. Den NTE ähnlich sind auch sogenannte Nachtod-erfahrungen sowie spontane Erlebnisse, die im Rahmen anderer außergewöhnlicher Stresssituationen auftreten. Von Nachtoderfahrungen spricht man, wenn die Betroffenen anlässlich des Todes von geliebten Angehörigen oder Freunden Erlebnisse haben, die inhaltlich ebenfalls, zumindest aber teilweise, denen von NTE entsprechen. Nachtoderfahrungen sowie spontane NTE-ähnliche Erlebnisse unterscheiden sich jedoch von den echten NTE zumeist sowohl quantitativ als auch qualitativ. Unter einem quantitativen Unterschied versteht man in diesem Zusammenhang eine in der Regel geringer ausgeprägte Komplexität, als sie sehr vielen NTE zu eigen ist. Da sich aber auch viele NTE selbst bezüglich ihrer Komplexität unterscheiden, ist der Hauptunterschied qualitativer Natur: Echte NTE besitzen gegenüber den anderen hier erwähnten Phänomenen eine größere inhaltliche und emotionale Tiefe. Sie begleiten die Betroffenen anschließend ein Leben lang – zumeist mit positiven, in Einzelfällen aber auch mit negativen Folgen, die bis zu einem späteren Suizid reichen können. Die genannten außergewöhnlichen Bewusstseinsphänomene lassen sich in ihrer Gesamtheit bei rund 5 % der Bevölkerung finden. NTE im Speziellen haben hiervon einen durchaus bedeutenden Anteil. Je nach Studie geben zwischen 18 % und 40 % aller Personen, die reanimiert wurden, an, währenddessen eine NTE erlebt zu haben. Dass nicht alle eine solche Erfahrung machen, wird von Kritikern gern dahingehend interpretiert, NTE seien rein physiologischer und keineswegs spiritueller Natur. Jedoch sollte man bedenken, dass im Fall einer rein neurophysiologischen Grundlage von NTE dann bei jedem ein solches Phänomen zu erwarten wäre, so wie beispielsweise auch die Symptome einer Hypoglykämie im Wesentlichen immer dieselben sind. Y1 - 2014 U6 - https://doi.org/10.1055/s-0034-1387363 SN - 1439-4413 (E-Journal); 0012-0472 (Print); 1437-5982 (Print) VL - Jg. 139 IS - H. 51/52 SP - 2651 EP - 2654 PB - Thieme CY - Stuttgart ER - TY - JOUR A1 - Balzer, Hermann T1 - Ausgestaltung und Steuerung des Netzes von Bankbeziehungen - Update nach 25 Jahren mithilfe einer explorativen Unternehmensbefragung / Arbeitskreis Finanzierung der Schmalenbach-Gesellschaft e.V. unter Mitarb. von Prof. Dr. Hermann Balzer... JF - Zfbf : Schmalenbachs Zeitschrift für betriebswirtschaftliche Forschung Y1 - 2014 SN - 0341-2687 IS - H. 8 SP - 694 EP - 723 PB - Springer Gabler CY - Wiesbaden ER - TY - JOUR A1 - Guo, Yuanyuan A1 - Seki, Kosuke A1 - Miyamoto, Ko-ichiro A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Device simulation of the light-addressable potentiometric sensor with a novel photoexcitation method for a higher spatial resolution JF - Procedia Engineering N2 - A novel photoexcitation method for the light-addressable potentiometric sensor (LAPS) realized a higher spatial resolution of chemical imaging. In this method, a modulated light probe, which generates the alternating photocurrent signal, is surrounded by a ring of constant light, which suppresses the lateral diffusion of photocarriers by enhancing recombination. A device simulation verified that a higher spatial resolution could be obtained by adjusting the gap between the modulated and constant light. It was also found that a higher intensity and a longer wavelength of constant light was more effective. However, there exists a tradeoff between the spatial resolution and the amplitude of the photocurrent, and thus, the signal-to-noise ratio. A tilted incidence of constant light was applied, which could achieve even higher resolution with a smaller loss of photocurrent. KW - Light-addressable Potentiometric Sensor KW - novel photoexcitation method KW - tilted constant illumination KW - spatial resolution Y1 - 2014 U6 - https://doi.org/10.1016/j.proeng.2014.11.369 SN - 1877-7058 N1 - EUROSENSORS 2014 ; European Conference on Solid-State Transducers <28, 2014> VL - 87 SP - 456 EP - 459 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Miyamoto, K. A1 - Seki, K. A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, T. T1 - Enhancement of the spatial resolution of the chemical imaging sensor by a hybrid fiber-optic illumination JF - Procedia Engineering N2 - The chemical imaging sensor, which is based on the principle of the light-addressable potentiometric sensor (LAPS), is a powerful tool to visualize the spatial distribution of chemical species on the sensor surface. The spatial resolution of this sensor depends on the diffusion of photocarriers excited by a modulated light. In this study, a novel hybrid fiber-optic illumination was developed to enhance the spatial resolution. It consists of a modulated light probe to generate a photocurrent signal and a ring of constant light, which suppresses the lateral diffusion of minority carriers excited by the modulated light. It is demonstrated that the spatial resolution was improved from 92 μm to 68 μm. Y1 - 2014 U6 - https://doi.org/10.1016/j.proeng.2014.11.563 SN - 1877-7058 N1 - EUROSENSORS 2014 ; European Conference on Solid-State Transducers <28, 2014> VL - 87 SP - 612 EP - 615 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bronder, Thomas A1 - Wu, Chunsheng A1 - Poghossian, Arshak A1 - Werner, Frederik A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Label-free detection of DNA hybridization with light-addressable potentiometric sensors: comparison of various DNA-immobilization strategies JF - Procedia Engineering N2 - Light-addressable potentiometric sensors (LAPS) consisting of a p-Si-SiO2 and p-Si-SiO2-Au structure, respectively, have been tested for a label-free electrical detection of DNA (deoxyribonucleic acid) hybridization. Three different strategies for immobilizing single-stranded probe DNA (ssDNA) molecules on a LAPS surface have been studied and compared: (a) immobilization of thiol-modified ssDNA on the patterned Au surface via gold-thiol bond, (b) covalent immobilization of amino-modified ssDNA onto the SiO2 surface functionalized with 3-aminopropyltriethoxysilane and (c) layer-by-layer adsorption of negatively charged ssDNA on a positively charged weak polyelectrolyte layer of poly(allylamine hydrochloride). KW - LAPS KW - lable-free detection KW - DNA hybridization KW - field-effect sensor Y1 - 2014 U6 - https://doi.org/10.1016/j.proeng.2014.11.647 SN - 1877-7058 N1 - EUROSENSORS 2014 ; European Conference on Solid-State Transducers <28, 2014> VL - 87 SP - 755 EP - 758 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Huck, Christina A1 - Poghossian, Arshak A1 - Bäcker, Matthias A1 - Reisert, Steffen A1 - Schubert, J. A1 - Zander, W. A1 - Begoyan, V. K. A1 - Buniatyan, V. V. A1 - Schöning, Michael Josef T1 - Chemical sensors based on a high-k perovskite oxide of barium strontium titanate JF - Procedia Engineering N2 - High-k perovskite oxide of barium strontium titanate (BST) represents a very attractive multi-functional transducer material for the development of (bio-)chemical sensors for liquids. In this work, BST films have been applied as a sensitive transducer material for a label-free detection of adsorbed charged macromolecules (positively charged polyelectrolytes) and concentration of hydrogen peroxide vapor as well as protection insulator layer for a contactless electrolyte-conductivity sensor. The experimental results of characterization of individual sensors are presented. Special emphasis is devoted towards the development of a capacitively-coupled contactless electrolyte-conductivity sensor. KW - barium strontium titanate KW - high-k material KW - contactless conductivity sensor KW - multi-functional material KW - hydrogen peroxide Y1 - 2014 U6 - https://doi.org/10.1016/j.proeng.2014.11.258 SN - 1877-7058 N1 - EUROSENSORS 2014 ; European Conference on Solid-State Transducers <28, 2014> VL - 87 SP - 28 EP - 31 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schusser, Sebastian A1 - Bäcker, Matthias A1 - Krischer, M. A1 - Wenzel, L. A1 - Leinhos, Marcel A1 - Poghossian, Arshak A1 - Biselli, Manfred A1 - Wagner, P. A1 - Schöning, Michael Josef T1 - Enzymatically catalyzed degradation of biodegradable polymers investigated by means of a semiconductor-based field-effect sensor JF - Procedia Engineering N2 - A semiconductor field-effect device has been used for an enzymatically catalyzed degradation of biopolymers for the first time. This novel technique is capable to monitor the degradation process of multiple samples in situ and in real-time. As model system, the degradation of the biopolymer poly(D, L-lactic acid) has been monitored in the degradation medium containing the enzyme lipase from Rhizomucor miehei. The obtained results demonstrate the potential of capacitive field-effect sensors for degradation studies of biodegradable polymers. KW - Field-effect sensor KW - enzymatic (bio)degradation KW - poly(d, l-lactic acid) KW - in-situ monitoring KW - impedance spectroscopy Y1 - 2014 U6 - https://doi.org/10.1016/j.proeng.2014.11.689 SN - 1877-7058 N1 - EUROSENSORS 2014 ; European Conference on Solid-State Transducers <28, 2014> VL - 87 SP - 1314 EP - 1317 PB - Elsevier CY - Amsterdam 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 - https://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 - Eilmann, Britta A1 - Sterck, Frank J. A1 - Wegner, L. A1 - de Vries, Sven M. G. A1 - von Arx, G. A1 - Mohren, Godefridus M. J. A1 - den Ouden, Jan A1 - Sass-Klaassen, Ute G. W. T1 - Wood structural differences between northern and southern beech provenances growing at a moderate site JF - Tree Physiology Y1 - 2014 U6 - https://doi.org/10.1093/treephys/tpu069 SN - 1758-4469 (Online) SN - 0829-318X (Print) VL - 34 IS - 8 SP - 882 EP - 893 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Lévesque, Mathieu A1 - Siegwolf, Rolf A1 - Eilmann, Britta A1 - Saurer, Matthias A1 - Rigling, Andreas T1 - Increased water-use efficiency does not lead to enhanced tree growth under xeric and mesic conditions JF - New Phytologist Y1 - 2014 U6 - https://doi.org/10.1111/nph.12772 SN - 1469-8137 (Online) SN - 0028-646X (Print) VL - 203 IS - 1 SP - 94 EP - 109 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Stulpe, Werner T1 - From the attempt of certain classical reformulations of quantum mechanics to quasi-probability representations JF - Journal of Mathematical Physics N2 - The concept of an injective affine embedding of the quantum states into a set of classical states, i.e., into the set of the probability measures on some measurable space, as well as its relation to statistically complete observables is revisited, and its limitation in view of a classical reformulation of the statistical scheme of quantum mechanics is discussed. In particular, on the basis of a theorem concerning a non-denseness property of a set of coexistent effects, it is shown that an injective classical embedding of the quantum states cannot be supplemented by an at least approximate classical description of the quantum mechanical effects. As an alternative approach, the concept of quasi-probability representations of quantum mechanics is considered. Y1 - 2014 U6 - https://doi.org/10.1063/1.4861939 SN - 222-488 N1 - bereits unter gleichem Titel aufgenommen bei arxiv : http://arxiv.org/pdf/1307.2314.pdf VL - 55 IS - 1 PB - AIP Publishing CY - College Park, Md. 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 - https://doi.org/10.3189/2014AoG65A004 SN - 1727-5644 VL - 55 IS - 65 SP - 14 EP - 22 PB - Cambridge University Press CY - Cambridge ER - TY - JOUR A1 - Bäcker, Matthias A1 - Schusser, Sebastian A1 - Poghossian, Arshak A1 - Schöning, Michael Josef T1 - Multi-Parametererfassung mit siliziumbasiertem Sensorchip: Aus Drei mach Eins JF - GIT Labor-Fachzeitschrift Y1 - 2014 SN - 0016-3538 IS - 2 SP - 28 EP - 30 PB - Wiley ER - TY - JOUR A1 - Almajhdi, Fahad N. A1 - Senger, Tilo A1 - Amer, Haitham M. A1 - Gissmann, Lutz A1 - Öhlschläger, Peter T1 - Design of a highly effective therapeutic HPV16 E6/E7-specific DNA vaccine: optimization by different ways of sequence rearrangements (Shuffling) JF - PLOS one N2 - Persistent infection with the high-risk Human Papillomavirus type 16 (HPV 16) is the causative event for the development of cervical cancer and other malignant tumors of the anogenital tract and of the head and neck. Despite many attempts to develop therapeutic vaccines no candidate has entered late clinical trials. An interesting approach is a DNA based vaccine encompassing the nucleotide sequence of the E6 and E7 viral oncoproteins. Because both proteins are consistently expressed in HPV infected cells they represent excellent targets for immune therapy. Here we report the development of 8 DNA vaccine candidates consisting of differently rearranged HPV-16 E6 and E7 sequences within one molecule providing all naturally occurring epitopes but supposedly lacking transforming activity. The HPV sequences were fused to the J-domain and the SV40 enhancer in order to increase immune responses. We demonstrate that one out of the 8 vaccine candidates induces very strong cellular E6- and E7- specific cellular immune responses in mice and, as shown in regression experiments, efficiently controls growth of HPV 16 positive syngeneic tumors. This data demonstrates the potential of this vaccine candidate to control persistent HPV 16 infection that may lead to malignant disease. It also suggests that different sequence rearrangements influence the immunogenecity by an as yet unknown mechanism. Y1 - 2014 U6 - https://doi.org/10.1371/journal.pone.0113461 SN - 1932-6203 VL - 11 IS - 9 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Wollert, Jörg T1 - Funkstandards für Sensornetzwerke JF - Elektronik : Fachmedium für industrielle Anwender und Entwickler Y1 - 2014 SN - 0013-5658 VL - Bd. 63 IS - H. 12 SP - 36 EP - 41 PB - WEKA-Fachmedien CY - Haar ER - TY - JOUR A1 - Wollert, Jörg T1 - Echtzeit-Ethernet : Protokoll-Reigen JF - Elektronik : Fachmedium für industrielle Anwender und Entwickler Y1 - 2014 SN - 0013-5658 VL - Bd. 63 IS - H. 26 SP - 24 EP - 31 PB - WEKA-Fachmedien CY - Haar ER - TY - JOUR A1 - Wollert, Jörg T1 - Der Embedded Wireless-Report JF - Elektronik : Fachmedium für industrielle Anwender und Entwickler ; Sonderh. Wireless : Fachmedium für Entwicklungen funkbasierter Systeme Y1 - 2014 SN - 0013-5658 SP - 18 EP - 25 PB - WEKA-Fachmedien CY - Haar ER - TY - JOUR A1 - Wollert, Jörg T1 - Echtzeit-Ethernet mit Standardtechnik JF - Elektronik : Fachmedium für industrielle Anwender und Entwickler ; Sonderh. Embedded : Fachmagazin für die Entwicklung von Embedded-Systemen Y1 - 2014 SN - 0013-5658 VL - Bd. 63 IS - H. 12 SP - 28 EP - 32 PB - WEKA-Fachmedien CY - Haar ER - TY - JOUR A1 - Wollert, Jörg T1 - Feldbustechnologie JF - Factory : der Durchblick in der Technik Y1 - 2014 SP - Publ. online PB - WEKA-Industriemedien CY - Wien ER - TY - JOUR A1 - Wallenborn, Ramona A1 - Ritz, Thomas T1 - Mobilität miteinander teilen : städtisches eCarsharing in einer vernetzten Gesellschaft ; [vernetztes Fahren von morgen] JF - Neue Mobilität : das Magazin vom Bundesverband eMobilität Y1 - 2014 SN - 2191-5636 VL - 5 IS - 14 (Herbstausg.) SP - 92 EP - 95 PB - Bundesverband eMobilität BEM CY - Berlin ER - TY - JOUR A1 - Demny, Andreas A1 - Hebel, Christoph T1 - Rechnergestützte Ermittlung der Verbindungsfunktionsstufen und der verbindungsbezogenen Angebotsqualität nach den Richtlinien für integrierte Netzgestaltung nach RIN 2008 JF - Straßenverkehrstechnik : Organ der Forschungsgesellschaft für Straßen- und Verkehrswesen, der Bundesvereinigung der Straßenbau- und Verkehrsingenieure und der Österreichischen Forschungsgesellschaft Straße und Verkehr ; Zeitschrift für Verkehrsplanung, Verkehrsmanagement, Verkehrssicherheit, Verkehrstechnik Y1 - 2014 SN - 0039-2219 VL - Jg. 58 IS - H. 12 SP - 811 EP - 820 PB - Kirschbaum Verlag CY - Bonn ER - TY - JOUR A1 - Thomas, Axel T1 - Generation Y JF - P.T. : Magazin für Wirtschaft und Gesellschaft Y1 - 2014 SN - 1860-501X VL - 10 IS - 3 SP - 6 EP - 9 PB - OPS Netzwerk CY - Leipzig ER - TY - JOUR A1 - Thomas, Axel A1 - Wassenberg, Gerd T1 - Erfolgreich sein im Kampf um die besten Talente : Employer Branding JF - Wirtschaftliche Nachrichten der Industrie- und Handelskammer Aachen Y1 - 2014 N1 - Nur noch nach Anfrage bei der IHK Aachen erhältlich: https://www.ihk.de/aachen/servicemarken/presse/medien-der-ihk/wirtschaftliche-nachrichten/aktuelle-ausgaben PB - IHK Aachen CY - Aachen ER - TY - JOUR A1 - Ritz, Thomas A1 - Pisarczyk, Rafael A1 - Sachtleben, Johanna A1 - Leßenich, Nina T1 - Usability Engineering maßgeschneidert : Modellbaukasten zur Entwicklung gebrauchstauglicher mobiler Software JF - Wissenschaft trifft Praxis Y1 - 2014 SN - 2198-8544 (Print) SN - 2198-9362 (Online) N1 - Der Link führt zum vollständigen Heft, der Artikel beginnt auf S.79. VL - 1 IS - 1 SP - 79 EP - 88 PB - Begleitforschung Mittelstand-Digital c/o WIK-Consult GmbH CY - Bad Honnef ER - TY - JOUR A1 - Martin-Gonzalez, Anabel A1 - Kotliar, Konstantin A1 - Rios-Martinez, Jorge A1 - Lanzl, Ines A1 - Navab, Nassir T1 - Mediated-reality magnification for macular degeneration rehabilitation JF - Journal of Modern Optics Y1 - 2014 U6 - https://doi.org/10.1080/09500340.2014.936110 SN - 1362-3044 VL - 61 IS - 17 SP - 1400 EP - 1408 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Gellert, Christoph A1 - Butenweg, Christoph T1 - Seismic analysis of masonry structures in German earthquake zones according to DIN EN 1998-1 T1 - Erdbebenbemessung von Mauerwerksbauten in deutschen Erdbebengebieten nach DIN EN 1998-1 JF - Mauerwerk : European journal of masonry N2 - Die Erdbeben in Albstadt 1978 (Magnitude 5,7), Roermond 1992 (Magnitude 5,9) oder in Waldkirch 2004 (Magnitude 5,1) haben verdeutlicht, dass die erdbebensichere Auslegung von Mauerwerksbauten auch in Deutschland von großer Bedeutung ist. Bereits im Jahr 1981 wurde die DIN 4149 (1981) “Bauten in deutschen Erdbebengebieten – Lastannahmen, Bemessung und Ausführung üblicher Hochbauten“ eingeführt, in der aber für Mauerwerksbauten nur wenige Anforderungen gestellt wurden. Diese Norm wurde durch den NABau-Arbeitsausschuss “Erdbeben; Sonderfragen“ des Deutschen Instituts für Normung e.V. (DIN) auf Grundlage des Eurocode 8 (2004) vollständig überarbeitet und durch die DIN 4149 (2005) abgelöst, die umfangreiche Regelungen für die seismische Auslegung von Mauerwerksbauten enthält. Mittlerweile liegen die DIN EN 1998-1 (2010) und der Nationale Anhang DIN EN 1998-1/NA (2011) vor, die nach Einarbeitung der Ergebnisse der durchgeführten Anwendungserprobung bauaufsichtlich eingeführt und die DIN 4149 (2005) ersetzen werden. Der folgende Beitrag gibt einen Überblick über die seismische Berechnung und Bemessung von Mauerwerksbauten nach dem europäischen Regelwerk und illustriert deren Anwendung an einem baupraktischen Beispiel. Y1 - 2014 U6 - https://doi.org/10.1002/dama.201400626 SN - 1437-1022 (E-Journal); 1432-3427 (Print) VL - 18 IS - 3-4 SP - 188 EP - 196 PB - Ernst & Sohn CY - Berlin ER - TY - JOUR A1 - Butenweg, Christoph A1 - Meyer, Udo A1 - Fehling, Ekkehard T1 - EU-Projekt INSYSME: Innovative Techniken für erdbebensichere Ausfachungswände aus Ziegelmauerwerk in Stahlbetonrahmentragwerken JF - Mauerwerk : European journal of masonry N2 - Am 1. Oktober 2013 ist das auf drei Jahre angelegte EU-Forschungsprojekt INSYSME – Innovative Systeme für erdbebentaugliche Ausfachungswände aus Ziegelmauerwerk in Stahlbetonrahmentragwerken – gestartet. Unter der Koordination der Universität Padua beteiligen sich 16 Partner aus sechs europäischen Ländern (Deutschland, Griechenland, Italien, Portugal, Rumänien, Türkei). Als deutsche Partner nehmen die Arbeitsgemeinschaft Mauerziegel aus Bonn, die Universität Kassel sowie das Ingenieurbüro SDA-engineering GmbH aus Herzogenrath, teil. Ziel der deutschen Partner ist die Entwicklung von innovativen Ausfachungssystemen aus monolithischem wärmedämmenden Ziegelmauerwerk, mit denen nicht nur eine erhöhte Erdbebensicherheit, sondern auch die sichere Erfüllung der steigenden Anforderungen aus Windbeanspruchungen gewährleistet werden können. Die Forschungsergebnisse sollen vom Partner SDA-engineering GmbH in die bereits seit einigen Jahren verfügbare Softwarelösung MINEA [1] integriert werden. Weitere Informationen stehen auf den Websites des Projektes [2] zur Verfügung. Im vorliegenden Beitrag werden nach einer kurzen thematischen Einführung die Ergebnisse von Tastversuchen an senkrecht zur Ebene belasteten Ausfachungswänden aus Planziegelmauerwerk vorgestellt. Im Anschluss wird das geplante Arbeitsprogramm der deutschen Partner im Projekt INSYSME beschrieben. Y1 - 2014 U6 - https://doi.org/10.1002/dama.201400612 SN - 1437-1022 (E-Journal); 1432-3427 (Print) VL - 18 IS - 2 SP - 78 EP - 81 PB - Ernst & Sohn CY - Berlin ER - TY - JOUR A1 - Butenweg, Christoph A1 - Schmitt, Timo A1 - Rosen, Britta T1 - Seismische Einwirkungen auf erdverlegte Rohrleitungssysteme JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen ; offizielle Zeitschrift der VDI-Gesellschaft Bautechnik Y1 - 2014 SN - 0005-6650 VL - 89 (2014) IS - Heft 7/8 SP - 316 EP - 324 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Meyer, Udo A1 - Butenweg, Christoph A1 - Fehling, Ekkehard T1 - EU-Projekt INSYSME : innovative Systeme für erdbebentaugliche Ausfachungswände aus Ziegelmauerwerk JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen ; offizielle Zeitschrift der VDI-Gesellschaft Bautechnik. Beilage: D-A-CH-Mitteilungsblatt Y1 - 2014 SN - 1436-4867 (E-Journal); 0005-6650 (Print) VL - 89 (2014) IS - April SP - S14 EP - S15 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Butenweg, Christoph A1 - Renault, Philippe T1 - Workshop der Gesellschaften zum EU-Projekt SHARE JF - Bauingenieur : die richtungsweisende Zeitschrift im Bauingenieurswesen ; offizielle Zeitschrift der VDI-Gesellschaft Bautechnik. Beilage: D-A-CH-Mitteilungsblatt Y1 - 2014 SN - 1436-4867 (E-Journal); 0005-6650 (Print) VL - 89 (2014) IS - Oktober SP - S2 EP - S3 PB - VDI Fachmedien CY - Düsseldorf ER - TY - JOUR A1 - Haag, S. A1 - Zontar, D. A1 - Schleupen, Josef A1 - Müller, T. A1 - Brecher, C. T1 - Chain of refined perception in self-optimizing assembly of micro-optical systems JF - Journal of sensors and sensor systems N2 - Today, the assembly of laser systems requires a large share of manual operations due to its complexity regarding the optimal alignment of optics. Although the feasibility of automated alignment of laser optics has been shown in research labs, the development effort for the automation of assembly does not meet economic requirements – especially for low-volume laser production. This paper presents a model-based and sensor-integrated assembly execution approach for flexible assembly cells consisting of a macro-positioner covering a large workspace and a compact micromanipulator with camera attached to the positioner. In order to make full use of available models from computer-aided design (CAD) and optical simulation, sensor systems at different levels of accuracy are used for matching perceived information with model data. This approach is named "chain of refined perception", and it allows for automated planning of complex assembly tasks along all major phases of assembly such as collision-free path planning, part feeding, and active and passive alignment. The focus of the paper is put on the in-process image-based metrology and information extraction used for identifying and calibrating local coordinate systems as well as the exploitation of that information for a part feeding process for micro-optics. Results will be presented regarding the processes of automated calibration of the robot camera as well as the local coordinate systems of part feeding area and robot base. Y1 - 2014 U6 - https://doi.org/10.5194/jsss-3-87-2014 SN - 2194-878X VL - 3 IS - 1 SP - 87 EP - 95 PB - Copernicus Publ. CY - Göttingen 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 - https://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 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - https://doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford 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 - https://doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER -