TY - JOUR A1 - Engelmann, Ulrich M. A1 - Roeth, Anjali A.J. A1 - Eberbeck, Dietmar A1 - Buhl, Eva Miriam A1 - Neumann, Ulf Peter A1 - Schmitz-Rode, Thomas A1 - Slabu, Ioana T1 - Combining Bulk Temperature and Nanoheating Enables Advanced Magnetic Fluid Hyperthermia Efficacy on Pancreatic Tumor Cells JF - Scientific Reports N2 - Many efforts are made worldwide to establish magnetic fluid hyperthermia (MFH) as a treatment for organ-confined tumors. However, translation to clinical application hardly succeeds as it still lacks of understanding the mechanisms determining MFH cytotoxic effects. Here, we investigate the intracellular MFH efficacy with respect to different parameters and assess the intracellular cytotoxic effects in detail. For this, MiaPaCa-2 human pancreatic tumor cells and L929 murine fibroblasts were loaded with iron-oxide magnetic nanoparticles (MNP) and exposed to MFH for either 30 min or 90 min. The resulting cytotoxic effects were assessed via clonogenic assay. Our results demonstrate that cell damage depends not only on the obvious parameters bulk temperature and duration of treatment, but most importantly on cell type and thermal energy deposited per cell during MFH treatment. Tumor cell death of 95% was achieved by depositing an intracellular total thermal energy with about 50% margin to damage of healthy cells. This is attributed to combined intracellular nanoheating and extracellular bulk heating. Tumor cell damage of up to 86% was observed for MFH treatment without perceptible bulk temperature rise. Effective heating decreased by up to 65% after MNP were internalized inside cells. Y1 - 2018 U6 - http://dx.doi.org/10.1038/s41598-018-31553-9 SN - 2045-2322 VL - 8 IS - 1 SP - Article number 13210 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Seifert, Julian A1 - Mues, Benedikt A1 - Roitsch, Stefan A1 - Ménager, Christine A1 - Schmidt, Annette M. A1 - Slabu, Ioana T1 - Heating efficiency of magnetic nanoparticles decreases with gradual immobilization in hydrogels JF - Journal of Magnetism and Magnetic Materials Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.jmmm.2018.09.113 SN - 0304-8853 VL - 471 IS - 1 SP - 486 EP - 494 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Engelmann, Ulrich M. A1 - Shasha, Carolyn A1 - Teeman, Eric A1 - Slabu, Iona A1 - Krishnan, Kannan M. T1 - Predicting size-dependent heating efficiency of magnetic nanoparticles from experiment and stochastic Néel-Brown Langevin simulation JF - Journal of Magnetism and Magnetic Materials Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.jmmm.2018.09.041 SN - 0304-8853 VL - 471 IS - 1 SP - 450 EP - 456 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Slabu, Ioana A1 - Roeth, Anjali A. A1 - Engelmann, Ulrich M. A1 - Wiekhorst, Frank A1 - Buhl, Eva M. A1 - Neumann, Ulf P. A1 - Schmitz-Rode, Thomas T1 - Modeling of magnetoliposome uptake in human pancreatic tumor cells in vitro JF - Nanotechnology Y1 - 2019 U6 - http://dx.doi.org/10.1088/1361-6528/ab033e SN - 1361-6528 VL - 30 IS - 18 SP - 184004 ER - TY - JOUR A1 - Engel, Mareike A1 - Gemünde, Andre A1 - Holtmann, Dirk A1 - Müller-Renno, Christine A1 - Ziegler, Christiane A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Clostridium acetobutylicum’s connecting world: cell appendage formation in bioelectrochemical systems JF - ChemElectroChem Y1 - 2019 U6 - http://dx.doi.org/10.1002/celc.201901656 SN - 2196-0216 IS - Accepted Article PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Digel, Ilya A1 - Akimbekov, N. A1 - Turalieva, M. A1 - Mansurov, Z. A1 - Temiz Artmann, Aysegül A1 - Eshibaev, A. A1 - Zhubanova, A. T1 - Usage of Carbonized Plant Wastes for Purification of Aqueous Solutions JF - Journal of Industrial Technology and Engineering Y1 - 2013 VL - 2 IS - 07 SP - 47 EP - 54 ER - TY - JOUR A1 - Karschuck, T. L. A1 - Filipov, Y. A1 - Bollella, P. A1 - Schöning, Michael Josef A1 - Katz, E. T1 - Not-XOR (NXOR) logic gate based on an enzyme-catalyzed reaction JF - International Journal of Unconventional Computing N2 - Enzyme-catalyzed reactions have been designed to mimic various Boolean logic gates in the general framework of unconventional biomolecular computing. While some of the logic gates, particularly OR, AND, are easy to realize with biocatalytic reactions and have been reported in numerous publications, some other, like NXOR, are very challenging and have not been realized yet with enzyme reactions. The paper reports on a novel approach to mimicking the NXOR logic gate using the bell-shaped enzyme activity dependent on pH values. Shifting pH from the optimum value to the acidic or basic values by using acid or base inputs (meaning 1,0 and 0,1 inputs) inhibits the enzyme reaction, while keeping the optimum pH (assuming 0,0 and 1,1 input combinations) preserves a high enzyme activity. The challenging part of the present approach is the selection of an enzyme with a well-demonstrated bell-shape activity dependence on the pH value. While many enzymes can satisfy this condition, we selected pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase as this enzyme has the optimum pH center-located on the pH scale allowing the enzyme activity change by the acidic and basic pH shift from the optimum value corresponding to the highest activity. The present NXOR gate is added to the biomolecular “toolbox” as a new example of Boolean logic gates based on enzyme reactions. Y1 - 2019 SN - 1548-7199 VL - 14 IS - 3-4 SP - 235 EP - 242 PB - Old City Publishing CY - Philadelphia ER - TY - JOUR A1 - Dantism, Shahriar A1 - Röhlen, Desiree A1 - Wagner, Torsten A1 - Wagner, P. A1 - Schöning, Michael Josef T1 - A LAPS-based differential sensor for parallelized metabolism monitoring of various bacteria JF - Sensors N2 - Monitoring the cellular metabolism of bacteria in (bio)fermentation processes is crucial to control and steer them, and to prevent undesired disturbances linked to metabolically inactive microorganisms. In this context, cell-based biosensors can play an important role to improve the quality and increase the yield of such processes. This work describes the simultaneous analysis of the metabolic behavior of three different types of bacteria by means of a differential light-addressable potentiometric sensor (LAPS) set-up. The study includes Lactobacillus brevis, Corynebacterium glutamicum, and Escherichia coli, which are often applied in fermentation processes in bioreactors. Differential measurements were carried out to compensate undesirable influences such as sensor signal drift, and pH value variation during the measurements. Furthermore, calibration curves of the cellular metabolism were established as a function of the glucose concentration or cell number variation with all three model microorganisms. In this context, simultaneous (bio)sensing with the multi-organism LAPS-based set-up can open new possibilities for a cost-effective, rapid detection of the extracellular acidification of bacteria on a single sensor chip. It can be applied to evaluate the metabolic response of bacteria populations in a (bio)fermentation process, for instance, in the biogas fermentation process. Y1 - 2019 U6 - http://dx.doi.org/10.3390/s19214692 SN - 1424-8220 VL - 19 IS - 21 PB - MDPI CY - Basel ER - TY - JOUR A1 - Aimenova, Zh. E. A1 - Digel, Ilya A1 - Eshibaev, А. А. T1 - Dynamics of accumulation of lagochirzin in Lagochilus setulosus phytomass during the growing season and also features of its cultivation in the conditions of a typical sierozem JF - KazNU Bulletin. Biology series N2 - L.setulosus is offered for creation of biopreparation «Setulin», possesing he- mostatic action, the basic reactant of biopreparation is diterpen – lagochirzin. Results under the maintenance and dynamics of diterpen lagochirzin accumula- tion in various parts of L.setulosus are presented: in roots, stalks, leaves, flowers and calyx lobes during the growing season, and also results on conditions of cultivation L.setulosus in the conditions of a typical sierozem are resulted. From the obtained data is visible, that the given species of a plant is endemic. It is established, that dynamics of accumulation of lagochirzin in phytomass accrues from the beginning to the middle of the growing season. The chemical analysis of L.setulosus on a localization of lagochirzin in various organs of a plant, has shown, that the greatest quantity of lagochirzin collects in calyx lobes of the plants. Also it is established, that L.setulosus can be cultivated in the conditions of the typical sierozem, a mineral food is necessary for the given species of plants of Lagochilus genus, except nitric fertilizers. Comparative studying of wild-growing and cultural forms of L.setulosus has shown, that in the cultivated phytomass of plants the maintenance of lagochirzin on 17-20 % higher than in the wild-growing species. Y1 - 2016 SN - 1563-0218 N1 - Original in russischer Sprache VL - 69 IS - 4 SP - 4 EP - 11 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - JOUR A1 - Akimbekov, N.Sh. A1 - Digel, Ilya A1 - Savitkaya, I.S. A1 - Zhubanova, A.A. A1 - Tastambek, K.T. T1 - Investigations of LPS endotoxin elimination in the flowing column conditions with the sorbent on the basis of carbonized rice husk JF - KazNU Bulletin. Biology series Y1 - 2013 SN - 1563-0218 N1 - Original in russischer Sprache VL - 57 IS - 1 SP - 124 EP - 127 ER - TY - JOUR A1 - Akimbekov, N. S. A1 - Digel, Ilya A1 - Tastambek, K. T. A1 - Zhubanova, A. A. T1 - Biocompatibility of carbonized rice husk with a rat heart cells line H9c2 JF - Experimental Biology Y1 - 2013 SN - 1563-0218 N1 - Original in russischer Sprache VL - 59 IS - 3/1 SP - 23 EP - 25 ER - TY - JOUR A1 - Akimbekov, N. Sh. A1 - Digel, Ilya A1 - Zhubanova, A. A. T1 - Investigation the Influence of Carbonized Material Based On Rice Husk on Viability and Migration of Fibroblasts in T3B3 Cell Culture JF - KazNU Bulletin. Biology series Y1 - 2013 SN - 1563-0218 N1 - Original in russischer Sprache VL - 59 IS - 3/1 SP - 20 EP - 23 ER - TY - JOUR A1 - Akimbekov, N.Sh. A1 - Digel, Ilya A1 - O´Heras, C. A1 - Tastambek, K.T. A1 - Savitskaya, I.S. A1 - Ualyeva, P.S. A1 - Mansurov, Z.A. A1 - Zhubanova, A.A. T1 - Adsorption of bacterial lipopolysaccharides on carbonized rice husks obtained in the batch experiments JF - Experimental Biology N2 - The scope of this study is the measurement of endotoxin adsorption rate for carbonized rice husk. It showed good adsorption properties for LPS. During the batch experiments, several techniques were used and optimized for improving the material’s adsorption behavior. Also, with the results obtained it was possible to differentiate the materials according to their adsorption capacity and kinetic characteristics. KW - surface modification KW - adsorption KW - carbonized rice husk KW - lipopolysaccharide Y1 - 2014 SN - 1563-0218 N1 - Original in russischer Sprache VL - 60 IS - 1/2 SP - 144 EP - 148 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - JOUR A1 - Akimbekov, N.Sh. A1 - Digel, Ilya A1 - O’Heras, C. A1 - Tastambek, K.T. A1 - Savitskaya, I.S. A1 - Ualyeva, P.S. A1 - Mansurov, Z.A. A1 - Zhubanova, A.A. T1 - Adsorption of bacterial lipopol ysaccharides on carbonized ri ce husks obtained in the batch experiments JF - KazNU Bulletin. Biology series Y1 - 2015 SN - 1563-0218 VL - 60 IS - No 1/2 SP - 144 EP - 148 ER - TY - JOUR A1 - Zhubanova, А. A1 - Mansurov, Z.A. A1 - Digel, Ilya A1 - Saviskaya, I.S. A1 - Akimbekov, N.Sh. T1 - Designing of Heterogeneous Nanobiocomposites for Biotechnology JF - KazNU Bulletin. Biology series Y1 - 2013 SN - 1563-0218 VL - 59 IS - No 3/1 SP - 89 EP - 93 ER - TY - JOUR A1 - Sagymbay, Altynay A1 - G.E., Nusupbaeva A1 - N.Zh, Tleumbetova A1 - A.S., Mutalieva A1 - Nurpeisova, Ainur A1 - D.B., Jussupova A1 - Digel, Ilya T1 - Molecular genetics features of the epidemic season 2017-2018 on the influenza in Kazakhstan JF - Eurasian Journal of Ecology Y1 - 2019 SN - 2617-7358 VL - 58 IS - 1 SP - 50 EP - 60 ER - TY - JOUR A1 - Akimbekov, N. Sh. A1 - Digel, Ilya A1 - Zhubanova, A. A. T1 - Advantages of creation of e-books in training of specialists biologists and biotechnologists JF - KazNU Bulletin. Biology series. N2 - The necessity of e-books as a primary of learning, its opportunities for realization of competence during training biologist and biotechnologist specialists are determined. Definitions and requirements to the e-books, its advantages in comparison with traditional textbooks, and the ways of creation of e-books in the SunRav BookEditor program are considered. KW - SunRav BookEditor KW - softs KW - distance learning KW - e-issues KW - e-books Y1 - 2014 SN - 1563-0218 VL - 60 IS - 1 SP - 249 EP - 252 PB - Al-Farabi Kazakh National University CY - Almaty ER - TY - JOUR A1 - Akimbekov, N. Sh. A1 - Zhubanova, A. A. A1 - Mansurov, Z. A. A1 - Digel, Ilya A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Use of Carbonized Rise Shell for the local treatment of wounds JF - Eurasian ChemTech Journal N2 - On the model of musculocutaneous wound in rats, the effect of applicative sorption by carbonized rise shell (CRS) on the healing of festering wound was studied. It has been shown, that cytological changes end with rapid scar formation. The use of CRS at the period of severe purulent wound contributes to its favorable course, prevents the development of complications of the animals from sepsis. Y1 - 2010 U6 - http://dx.doi.org/10.18321/ectj35 SN - 2522-4867 VL - 12 IS - 2 SP - 133 EP - 138 PB - Institute of Combustion Problems CY - Almaty ER - TY - JOUR A1 - Savitskaya, I. S. A1 - Kistaubayeva, A. S. A1 - Digel, Ilya A1 - Shokatayeva, D. H. T1 - Physicochemical and Antibacterial Properties of Composite Films Based on Bacterial Cellulose and Chitosan for Wound Dressing Materials JF - Eurasian Chemico-Technological Journal Y1 - 2017 U6 - http://dx.doi.org/10.18321/ectj670 SN - 2522-4867 VL - 19 IS - 3 SP - 255 EP - 264 ER - TY - JOUR A1 - Turaliyeva, M. A1 - Yeshibaev, A. A1 - Saparbekova, A. A1 - Akynova, L. A1 - Abildayeva, R. A1 - Sadenova, M. A1 - Sartayeva, K. A1 - Schieffer, Andre A1 - Digel, Ilya T1 - Species composition and injuriousness of stranger xylophilous fauna affecting indigenous urban dendroflora of Central Asia JF - Asian journal of microbiology, biotechnology & environmental sciences : AJMBES N2 - At the present time, one of the most serious environmental problems of Central Asia and South Kazakhstan is the ongoing large-scale deterioration of principal urban tree populations. Several major centers of massive spread of invasive plant pests have been found in urban dendroflora of this region. The degree of damage of seven most wide-spread aboriginal tree species was found to range from 21.4±1.1 to 85.4±1.8%. In particular, the integrity of the native communities of sycamore (Platanus spp.), willow (Salix spp.), poplar (Populus spp.) and elm (Ulmus spp.) is highly endangered. Our taxonomic analysis of the most dangerous tree pests of the region has revealed them as neobiontic xylophilous insects such as Cossus cossus L. (Order: Lepidoptera L.) Monochamus urussovi Fisch., Monochamus sutor L., Acanthocinus aedelis L. and Ñetonia aureate L. (Order: Coleoptera L.). We relate the origin of this threatening trend with the import of industrial wood in the mid 90’s of the last century that was associated with high degree of the constructional work in the region. Because of the absence of efficient natural predators of the pest species, the application of microbiological methods of the pest control and limitation is suggested. Y1 - 2016 SN - 0972-3005 VL - 18 IS - 2 SP - 359 EP - 366 PB - EM International ER - TY - JOUR A1 - Mansurov, Z. A1 - Digel, Ilya A1 - Biisenbaev, M. A1 - Savistkaya, I. A1 - Kistaubaeva, A. A1 - Akimbekov, N. A1 - Zhubanova, A. T1 - Bio-composite material on the basis of carbonized rice husk in biomedicine and environmental applications JF - Eurasian Chemico-Technological Journal Y1 - 2012 U6 - http://dx.doi.org/10.18321/ectj105 SN - 2522-4867 VL - 14 IS - 2 SP - 115 EP - 131 PB - Institute of Combustion Problems CY - Almaty ER - TY - JOUR A1 - Digel, Ilya A1 - Wehlitz, V. A1 - Kayser, Peter A1 - Figiel-Lange, A. A1 - Bassam, R. A1 - Rundstedt, F. von T1 - Suspension depletion approach for exemption of infected Solanum jasminoides cells from pospiviroids JF - Plant Pathology N2 - Despite numerous studies, viroid elimination from infected plants remains a very challenging task. This study introduces for the first time a novel ‘suspension depletion’ approach for exemption of Solanum jasminoides plants from viroids. The proposed method implies initial establishment of suspension cultures of the infected plant cells. The suspended cells were then physically treated (mild thermotherapy, 33 °C), which presumably delayed the replication of the viroid. The viroid concentration in the treated biomass was monitored weekly using pospiviroid-specific PCR. After 10–12 weeks of continuous treatment, a sufficient decrease in viroid concentration was observed such that the infection became undetectable by PCR. The treated single cells then gave rise to microcolonies on a solid culture medium and the obtained viroid-negative clones were further promoted to regenerate into viroid-free plants. Three years of accumulated experimental data suggests feasibility, broad applicability, and good efficacy of the proposed approach. Y1 - 2018 U6 - http://dx.doi.org/10.1111/ppa.12750 SN - 1365-3059 VL - 67 IS - 2 SP - 358 EP - 365 PB - Wiley CY - Oxford ER - TY - JOUR A1 - Matcha, Heike ED - Martens, B. T1 - Parametrized Systems: Conceiving of Buildings as Assemblies of Varied Parts JF - Real Time - Proceedings of the 33rd eCAADe Conference - Volume 2, Vienna University of Technology, Vienna, Austria, 16-18 September 2015 Y1 - 2015 SP - 143 EP - 148 ER - TY - JOUR A1 - Schael, S. A1 - Atanasyan, A. A1 - Berdugo, J. A1 - Bretz, T. A1 - Czupalla, Markus A1 - Dachwald, Bernd A1 - Doetinchem, P. von A1 - Duranti, M. A1 - Gast, H. A1 - Karpinski, W. A1 - Kirn, T. A1 - Lübelsmeyer, K. A1 - Maña, C. A1 - Marrocchesi, P.S. A1 - Mertsch, P. A1 - Moskalenko, I.V. A1 - Schervan, T. A1 - Schluse, M. A1 - Schröder, K.-U. A1 - Schultz von Dratzig, A. A1 - Senatore, C. A1 - Spies, L. A1 - Wakely, S.P. A1 - Wlochal, M. A1 - Uglietti, D. A1 - Zimmermann, J. T1 - AMS-100: The next generation magnetic spectrometer in space – An international science platform for physics and astrophysics at Lagrange point 2 JF - Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.nima.2019.162561 SN - 0168-9002 VL - 944 IS - 162561 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Herrmann, Ulf A1 - Schwarzenbart, Marc A1 - Dittmann-Gabriel, Sören T1 - Speicher statt Kohle. Integration thermischer Stromspeicher in vorhandene Kraftwerksstandorte JF - BWK : Das Energie-Fachmagazin Y1 - 2019 SN - 1436-4883 VL - 71 IS - 4 SP - 42 EP - 45 PB - Springer-VDI-Verl. CY - Düsseldorf ER - TY - JOUR A1 - Arreola, Julio A1 - Keusgen, Michael A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Combined calorimetric gas- and spore-based biosensor array for online monitoring and sterility assurance of gaseous hydrogen peroxide in aseptic filling machines JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.111628 SN - 0956-5663 VL - 143 IS - 111628 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Mennicken, Max A1 - Peter, Sophia Katharina A1 - Kaulen, Corinna A1 - Simon, Ulrich A1 - Karthäuser, Silvia T1 - Controlling the Electronic Contact at the Terpyridine/Metal Interface JF - The Journal of Physical Chemistry C Y1 - 2019 U6 - http://dx.doi.org/10.1021/acs.jpcc.9b05865 SN - 1932-7455 VL - 123 IS - 35 SP - 21367 EP - 21375 ER - TY - JOUR A1 - Savitskaya, I.S. A1 - Kistaubayeva, A.S. A1 - Ignatova, L.V. A1 - Digel, Ilya T1 - Antimicrobial and wound healing properties of a bacterial cellulose based material containing B. subtilis cells JF - Heliyon Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.heliyon.2019.e02592 SN - 2405-8440 VL - 5 IS - 10 SP - Artikelnummer e02592 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Delaittre, Guillaume T1 - Telechelic Poly(2-Oxazoline)s JF - European Polymer Journal Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.eurpolymj.2019.109281 SN - 0014-3057 IS - In Press, Journal Pre-proof, 109281 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Linder, Peter A1 - Beckler, Matthias A1 - Doerr, Leo A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Staat, Manfred A1 - Gossmann, Matthias T1 - A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions JF - Journal of Pharmacological and Toxicological Methods Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.vascn.2019.05.162 SN - 1056-8719 VL - 99 IS - Article number 106595 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Schieren, Mark A1 - Kleinschmidt, Joris A1 - Schmutz, Axel A1 - Loop, Torsten A1 - Gatzweiler, Karl-Heinz A1 - Staat, Manfred A1 - Wappler, Frank A1 - Defosse, Jerome T1 - Comparison of forces acting on maxillary incisors during tracheal intubation with different laryngoscopy techniques: a blinded manikin study JF - Anaesthesia Y1 - 2019 SN - 1365-2044 U6 - http://dx.doi.org/10.1111/anae.14815 N1 - Die Anhänge "Table S1 (Impact of sex and level of training on dental force. Results presented as median (IQR [range]) and n (%))" und "Appendix S1 (Measurement technique.)" stehen unter "Supporting Information" zum Download bereit. VL - 74 IS - 12 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Panc, Nicolae A1 - Contiu, Glad A1 - Bocanet, Vlad A1 - Thurn, Laura A1 - Sabau, Emilia T1 - The influence of cutting technology on surface wear hardness JF - Academic Journal of Manufacturing Engineering Y1 - 2019 SN - 1583-7904 VL - 17 IS - 3 SP - 205 EP - 210 ER - TY - JOUR A1 - Orzada, Stephan A1 - Solbach, Klaus A1 - Gratz, Marcel A1 - Brunheim, Sascha A1 - Fiedler, Thomas M. A1 - Johst, Sören A1 - Bitz, Andreas A1 - Shooshtary, Samaneh A1 - Abuelhaija, Asjraf A1 - Voelker, Maximilian N. A1 - Rietsch, Stefan H. G. A1 - Kraff, Oliver A1 - Maderwald, Stefan A1 - Flöser, Martina A1 - Oehmingen, Mark A1 - Quick, Harald H. A1 - Ladd, Mark E. T1 - A 32-channel parallel transmit system add-on for 7T MRI JF - Plos one Y1 - 2019 U6 - http://dx.doi.org/10.1371/journal.pone.0222452 ER - TY - JOUR A1 - Krome, Cornelia A1 - Höft, Jan A1 - Sander, Volker T1 - Clustering time series applied to energy markets JF - Energy Informatics Y1 - 2019 U6 - http://dx.doi.org/10.1186/s42162-019-0076-0 SN - 2520-8942 VL - 2 IS - Article numer 17 SP - 1 EP - 20 PB - Springer CY - Berlin ER - TY - JOUR A1 - Bhattarai, Aroj A1 - Staat, Manfred T1 - A computational study of organ relocation after laparoscopic pectopexy to repair posthysterectomy vaginal vault prolapse JF - Computer Methods in Biomechanics and Biomedical Engineering: Imaging & Visualization Y1 - 2019 U6 - http://dx.doi.org/10.1080/21681163.2019.1670095 SN - 2168-1171 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Wolisz, Henryk A1 - Schütz, Thomas A1 - Blanke, Tobias A1 - Hagenkamp, Markus A1 - Kohrn, Markus A1 - Wesseling, Mark A1 - Müller, Dirk T1 - Cost optimal sizing of smart buildings' energy system components considering changing end-consumer electricity markets JF - Energy Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.energy.2017.06.025 VL - 137 SP - 715 EP - 728 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Timme, Michael T1 - Die Unwirksamkeit von auf Öffnungsklauseln in Gemeinschaftsordnungen fußenden Beschlüssen JF - Monatsschrift für deutsches Recht Y1 - 2019 U6 - http://dx.doi.org/10.9785/mdtr-2019-731509 SN - 0340-1812 IS - 15 SP - 904 EP - 905 PB - Verlag Dr. Otto Schmidt CY - Köln ER - TY - JOUR A1 - Leschinger, Tim A1 - Besch, Katharina A1 - Aydin, Cansu A1 - Staat, Manfred A1 - Scaal, Martin A1 - Müller, Lars Peter A1 - Wegmann, Kilian T1 - Irreparable rotator cuff tears: a biomechanical comparison of superior capsuloligamentous complex reconstruction techniques and an interposition graft technique JF - The Orthopaedic Journal of Sports Medicine Y1 - 2019 U6 - http://dx.doi.org/10.1177/2325967119864590 VL - 7 IS - 8 SP - 1 EP - 5 ER - TY - JOUR A1 - Jildeh, Zaid B. A1 - Kirchner, Patrick A1 - Baltes, Klaus A1 - Wagner, Patrick H. A1 - Schöning, Michael Josef T1 - Development of an in-line evaporation unit for the production of gas mixtures containing hydrogen peroxide – numerical modeling and experimental results JF - International Journal of Heat and Mass Transfer N2 - Hydrogen peroxide (H2O2) is a typical surface sterilization agent for packaging materials used in the pharmaceutical, food and beverage industries. We use the finite-elements method to analyze the conceptual design of an in-line thermal evaporation unit to produce a heated gas mixture of air and evaporated H2O2 solution. For the numerical model, the required phase-transition variables of pure H2O2 solution and of the aerosol mixture are acquired from vapor-liquid equilibrium (VLE) diagrams derived from vapor-pressure formulations. This work combines homogeneous single-phase turbulent flow with heat-transfer physics to describe the operation of the evaporation unit. We introduce the apparent heat-capacity concept to approximate the non-isothermal phase-transition process of the H2O2-containing aerosol. Empirical and analytical functions are defined to represent the temperature- and pressure-dependent material properties of the aqueous H2O2 solution, the aerosol and the gas mixture. To validate the numerical model, the simulation results are compared to experimental data on the heating power required to produce the gas mixture. This shows good agreement with the deviations below 10%. Experimental observations on the formation of deposits due to the evaporation of stabilized H2O2 solution fits the prediction made from simulation results. Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.ijheatmasstransfer.2019.118519 SN - 0017-9310 VL - 143 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Ermolaev, AP A1 - Erichev, VP A1 - Antonov, AA A1 - Grigoryan, GL A1 - Kotliar, Konstantin A1 - Levitsky, YV A1 - Hderi, K A1 - Mazurova, YV T1 - Assessing retinal photosensitivity in patients with central vision impairment using a portable perimeter (a preliminary report) JF - Vestnik oftalmologii Y1 - 2019 U6 - http://dx.doi.org/10.17116/oftalma201913503146 N1 - Abstract in Englisch VL - 135 IS - 3 SP - 46 EP - 54 ER - TY - JOUR A1 - Turlybekuly, Amanzhol A1 - Pogrebnjak, Alexander A1 - Sukhodub, L. F. A1 - Sukhodub, Liudmyla B. A1 - Kistaubayeva, A. S. A1 - Savitskaya, Irina A1 - Shokatayeva, D. H. A1 - Bondar, Oleksandr V. A1 - Shaimardanov, Z. K. A1 - Plotnikov, Sergey V. A1 - Shaimardanova, B. H. A1 - Digel, Ilya T1 - Synthesis, characterization, in vitro biocompatibility and antibacterial properties study of nanocomposite materials based on hydroxyapatite-biphasic ZnO micro- and nanoparticles embedded in Alginate matrix JF - Materials Science and Engineering C Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.msec.2019.109965 VL - 104 IS - Article number 109965 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Werkhausen, Amelie A1 - Cronin, Neil J. A1 - Albracht, Kirsten A1 - Bojsen-Møller, Jens A1 - Seynnes, Olivier R. T1 - Distinct muscle-tendon interaction during running at different speeds and in different loading conditions JF - Journal of Applied Physiology Y1 - 2019 U6 - http://dx.doi.org/10.1152/japplphysiol.00710.2018 SN - 1522-1601 VL - 127 IS - 1 SP - 246 EP - 253 ER - TY - JOUR A1 - Ermolaev, A.P. A1 - Nivokov, I.A. A1 - Melnikova, L.I. A1 - Kotliar, Konstantin T1 - Сравнительная характеристика химического состава витреального содержимого кадаверных глаз и глаз с рефрактерной терминальной глаукомой T1 - Comparative characteristics of the chemical composition of vitreal contents of cadaver eyes and eyes with terminal refractory glaucoma JF - Vestnik oftalmologii N2 - Purpose — to compare the chemical elemental composition of vitreous cavity content taken from cadaveric eyes compared to samples taken from the eyes with terminal stage refractory glaucoma with decompensated intraocular pressure (IOP). Material and methods. The vitreous contents of the eyes from 2 groups were studied. The 1st group included 15 cadaveric eyes; the 2nd group included 15 eyes with refractory glaucoma in the terminal stage of the disease with decompensated IOP in patients with hypertension pain. The vitreal content samples were taken in the course of antiglaucoma surgery aimed at preserving the eye as an organ and involving employment of drainage in the vitreous cavity. The study of virtual contents was carried out on energy dispersive spectrometer Oxford X-Max 50 integrated into scanning electron microscope Zeiss EVO LS10. Results. Increased concentrations of Kalium and Phosphorus were detected in the vitreous content of cadaveric eyes compared with the vitreal content from the eyes with terminal glaucoma with decompensated IOP taken in vivo (K — 0.172/0.093; P — 0.045/0.025 mmol/L). In the vitreous cavity in the eyes with end-stage glaucoma with decompensated IOP, the concentration of Nitrogen was higher in comparison with human cadaver eyes (2.030/1.424 mmol/L). Conclusion. The increased concentrations of Kalium and Phosphorus in the vitreous content of cadaveric eyes is associated with postmortem autolytic processes and with the release of intracellular content in the destruction of cell membranes. The increased Nitrogen concentration in the vitreal contents of the eyes with terminal stage glaucoma with decompensated IOP may be associated with the presence of osmotically active nitrogen-containing compounds in the eyes with increased IOP. Y1 - 2018 U6 - http://dx.doi.org/10.17116/oftalma2018134051195 VL - 5 IS - 2 SP - 195 EP - 201 PB - Media Sfera CY - Moskau ER - TY - JOUR A1 - Hofmann, Till A1 - Limpert, Nicolas A1 - Mataré, Victor A1 - Schönitz, Sebastian A1 - Niemueller, Tim A1 - Ferrein, Alexander A1 - Lakemeyer, Gerhard T1 - The Carologistics RoboCup Logistics Team 2018 N2 - The Carologistics team participates in the RoboCup Logistics League for the seventh year. The RCLL requires precise vision, manipulation and path planning, as well as complex high-level decision making and multi-robot coordination. We outline our approach with an emphasis on recent modifications to those components. The team members in 2018 are David Bosen, Christoph Gollok, Mostafa Gomaa, Daniel Habering, Till Hofmann, Nicolas Limpert, Sebastian Schönitz, Morian Sonnet, Carsten Stoffels, and Tarik Viehmann. This paper is based on the last year’s team description. Y1 - 2018 ER - TY - JOUR A1 - Birkl, Josef A1 - Diendorfer, Gerhard A1 - Kern, Alexander A1 - Thern, Stephan T1 - Extrem hohe Blitzströme JF - Elektropraktiker N2 - Blitze sind nach wie vor eine enorme Schadensquelle für Personenschäden, Brände, mechanische Zerstörungen und insbesondere auch Überspannungen. Das zeigen nicht zuletzt aktuelle Statistiken der Schadensversicherer. Immer wieder gibt es Meldungen über extrem hohe Blitzströme, die natürlich auch zu großen Schäden und Zerstörungen führen können. Dabei werden Scheitelwerte von teilweise deutlich über 300 kA genannt. Dies wirft Fragen auf, da die „klassische“ Blitzstatistik (z. B. nach CIGRE und IEC [8][10]) bisher solche Werte nicht kennt. Diese extremen Blitzströme werden meist aus den Daten von Blitzortungssystemen ermittelt. Y1 - 2018 VL - 72 IS - 3 SP - 217 EP - 225 PB - Huss Medien CY - Berlin ER - TY - JOUR A1 - Matcha, Heike A1 - Ljubas, Ante A1 - Gueldemet, Harun ED - Kepczynska-Walczak, A. T1 - Printing a Coffee Bar: An investigation into mid-scale 3D printing JF - Computing for a better tomorrow - Proceedings of the 36th eCAADe Conference - Volume 2, Lodz University of Technology, Lodz, Poland, 19-21 September 2018 N2 - We present and discuss an exploration of the possibilities and properties of 3D printing with a printing space of 1 cubic meter, and how those can be integrated into architectural education through an experimental design and research course with students of architecture.We expand on issues presented at the eCAADe conference 2017 in Rome [Ref 6] by increasing the complexity and size of our prints, printing not a model to scale, but a full scale funtional prototype of a usable architectural object: A coffee bar. Y1 - 2018 SP - 59 EP - 68 ER - TY - JOUR A1 - König, Johannes Alexander A1 - Wolf, Martin T1 - GHOST: An Evaluated Competence Developing Game for Cybersecurity Awareness Training JF - International Journal on Advances in Security N2 - To train end users how to interact with digital systems is indispensable to ensure a strong computer security. 'Competence Developing Game'-based approaches are particularly suitable for this purpose because of their motivation-and simulation-aspects. In this paper the Competence Developing Game 'GHOST' for cybersecurity awareness trainings and its underlying patterns are described. Accordingly, requirements for an 'Competence Developing Game' based training are discussed. Based on these requirements it is shown how a game can fulfill these requirements. A supplementary game interaction design and a corresponding evaluation study is shown. The combination of training requirements and interaction design is used to create a 'Competence Developing Game'-based training concept. A part of these concept is implemented into a playable prototype that serves around one hour of play respectively training time. This prototype is used to perform an evaluation of the game and training aspects of the awareness training. Thereby, the quality of the game aspect and the effectiveness of the training aspect are shown. Y1 - 2018 SN - 1942-2636 VL - 11 IS - 3 & 4 SP - 274 EP - 287 PB - IARIA Journals ER - TY - JOUR A1 - Schmidt, Katharina A1 - Forkmann, Katarina A1 - Schultz, Heidrun A1 - Gratz, Marcel A1 - Bitz, Andreas A1 - Wiech, Katja A1 - Bingel, Ulrike T1 - Enhanced Neural Reinstatement for Evoked Facial Pain Compared With Evoked Hand Pain JF - The Journal of Pain Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.jpain.2019.03.003 SN - 1526-5900 IS - In Press, Corrected Proof PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Götten, Falk A1 - Havermann, Marc A1 - Braun, Carsten A1 - Gomez, Francisco A1 - Bil, Cees T1 - RANS Simulation Validation of a Small Sensor Turret for UAVs JF - Journal of Aerospace Engineering N2 - Recent Unmanned Aerial Vehicle (UAV) design procedures rely on full aircraft steady-state Reynolds-Averaged-Navier-Stokes (RANS) analyses in early design stages. Small sensor turrets are included in such simulations, even though their aerodynamic properties show highly unsteady behavior. Very little is known about the effects of this approach on the simulation outcomes of small turrets. Therefore, the flow around a model turret at a Reynolds number of 47,400 is simulated with a steady-state RANS approach and compared to experimental data. Lift, drag, and surface pressure show good agreement with the experiment. The RANS model predicts the separation location too far downstream and shows a larger recirculation region aft of the body. Both characteristic arch and horseshoe vortex structures are visualized and qualitatively match the ones found by the experiment. The Reynolds number dependence of the drag coefficient follows the trend of a sphere within a distinct range. The outcomes indicate that a steady-state RANS model of a small sensor turret is able to give results that are useful for UAV engineering purposes but might not be suited for detailed insight into flow properties. Y1 - 2019 U6 - http://dx.doi.org/10.1061/(ASCE)AS.1943-5525.0001055 SN - 1943-5525 VL - 32 IS - 5 PB - ASCE CY - New York ER - TY - JOUR A1 - Quittmann, Oliver J. A1 - Abel, Thomas A1 - Albracht, Kirsten A1 - Strüder, Heiko K. T1 - Reliability of muscular activation patterns and their alterations during incremental handcycling in able-bodied participants JF - Sports Biomechanics Y1 - 2019 U6 - http://dx.doi.org/10.1080/14763141.2019.1593496 SN - 1752-6116 IS - Article in press PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Schildt, Ph. A1 - Braun, Carsten A1 - Marzocca, P. T1 - Metric evaluating potentials of condition-monitoring approaches for hybrid electric aircraft propulsion systems JF - CEAS Aeronautical Journal Y1 - 2019 U6 - http://dx.doi.org/10.1007/s13272-019-00411-3 SN - 1869-5590 SP - 1 EP - 14 PB - Springer CY - Berlin ER - TY - JOUR A1 - Capri, Miriam A1 - Morsiani, Cristina A1 - Santoro, Aurelia A1 - Moriggi, Manuela A1 - Conte, Maria A1 - Martucci, Morena A1 - Bellavista, Elena A1 - Fabbri, Cristina A1 - Giampieri, Enrico A1 - Albracht, Kirsten A1 - Flück, Martin A1 - Ruoss, Severin A1 - Brocca, Lorenza A1 - Canepari, Monica A1 - Longa, Emanuela A1 - Giulio, Irene Di A1 - Bottinelli, Roberto A1 - Cerretelli, Paolo A1 - Salvioli, Stefano A1 - Gelfi, Cecilia A1 - Franceschi, Claudio A1 - Narici, Marco A1 - Rittweger, Jörn T1 - Recovery from 6-month spaceflight at the International Space Station: muscle-related stress into a proinflammatory setting JF - The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Y1 - 2019 U6 - http://dx.doi.org/10.1096/fj.201801625R VL - 33 IS - 4 SP - 5168 EP - 5180 ER - TY - JOUR A1 - Bartella, Alexander K. A1 - Kamal, Mohammad A1 - Scholl, Ingrid A1 - Schiffer, Stefan A1 - Steegmann, Julius A1 - Ketelsen, Dominik A1 - Hölzle, Frank W. A1 - Lethaus, Bernd T1 - Virtual reality in preoperative imaging in maxillofacial surgery: implementation of “the next level”? JF - British Journal of Oral and Maxillofacial Surgery Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bjoms.2019.02.014 SN - 0266-4356 VL - 57 IS - 7 SP - 644 EP - 648 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Thoma, Andreas A1 - Ravi, Sridhar T1 - Significance of parallel computing on the performance of Digital Image Correlation algorithms in MATLAB N2 - Digital Image Correlation (DIC) is a powerful tool used to evaluate displacements and deformations in a non-intrusive manner. By comparing two images, one of the undeformed reference state of a specimen and another of the deformed target state, the relative displacement between those two states is determined. DIC is well known and often used for post-processing analysis of in-plane displacements and deformation of specimen. Increasing the analysis speed to enable real-time DIC analysis will be beneficial and extend the field of use of this technique. Here we tested several combinations of the most common DIC methods in combination with different parallelization approaches in MATLAB and evaluated their performance to determine whether real-time analysis is possible with these methods. To reflect improvements in computing technology different hardware settings were also analysed. We found that implementation problems can reduce the efficiency of a theoretically superior algorithm such that it becomes practically slower than a suboptimal algorithm. The Newton-Raphson algorithm in combination with a modified Particle Swarm algorithm in parallel image computation was found to be most effective. This is contrary to theory, suggesting that the inverse-compositional Gauss-Newton algorithm is superior. As expected, the Brute Force Search algorithm is the least effective method. We also found that the correct choice of parallelization tasks is crucial to achieve improvements in computing speed. A poorly chosen parallelisation approach with high parallel overhead leads to inferior performance. Finally, irrespective of the computing mode the correct choice of combinations of integerpixel and sub-pixel search algorithms is decisive for an efficient analysis. Using currently available hardware realtime analysis at high framerates remains an aspiration. Y1 - 2019 SP - 1 EP - 17 ER - TY - JOUR A1 - Bucur, Alexandru A1 - Lazarescu, Lucian A1 - Pop, Grigore Marian A1 - Achimas, Gheorghe A1 - Gebhardt, Andreas T1 - Tribological performance of biodegradable lubricants under different surface roughness of tools JF - Academic Journal of Manufacturing Engineering Y1 - 2019 SN - 1583-7904 VL - 17 IS - 1 SP - 172 EP - 178 ER - TY - JOUR A1 - Schwarz, Alexander A1 - Gebhardt, Andreas A1 - Schleser, Markus A1 - Popoola, Patricia T1 - New Welding Joint Geometries Manufactured by Powder Bed Fusion from 316L JF - Materials Performance and Characterization 8 Y1 - 2019 U6 - http://dx.doi.org/10.1520/MPC20180096 SN - 2379-1365 IS - in press ER - TY - JOUR A1 - Iken, Heiko A1 - Bronder, Thomas A1 - Goretzki, Alexander A1 - Kriesel, Jana A1 - Ahlborn, Kristina A1 - Gerlach, Frank A1 - Vonau, Winfried A1 - Zander, Willi A1 - Schubert, Jürgen A1 - Schöning, Michael Josef T1 - Development of a Combined pH- and Redox-Sensitive Bi-Electrode Glass Thin-Film Sensor JF - physica status solidi a : applications and materials sciences Y1 - 2019 U6 - http://dx.doi.org/10.1002/pssa.201900114 SN - 1862-6319 VL - 216 IS - 12 SP - 1 EP - 8 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Dantism, Shahriar A1 - Röhlen, Desiree A1 - Selmer, Thorsten A1 - Wagner, Torsten A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Quantitative differential monitoring of the metabolic activity of Corynebacterium glutamicum cultures utilizing a light-addressable potentiometric sensor system JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.111332 VL - 139 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Noureddine, Yacine A1 - Kraff, Oliver A1 - Ladd, Mark E. A1 - Wrede, Karsten A1 - Chen, Bixia A1 - Quick, Harald H. A1 - Schaefers, Georg A1 - Bitz, Andreas T1 - Radiofrequency induced heating around aneurysm clips using a generic birdcage head coil at 7 Tesla under consideration of the minimum distance to decouple multiple aneurysm clips JF - Magnetic Resonance in Medicine Y1 - 2019 U6 - http://dx.doi.org/10.1002/mrm.27835 SN - 1522-2594 IS - Early view SP - 1 EP - 17 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Valero, Daniel A1 - Chanson, Hubert A1 - Bung, Daniel B. T1 - Robust estimators for turbulence properties assessment Y1 - 2019 SP - 1 EP - 24 ER - TY - JOUR A1 - Gerhards, Michael A1 - Sander, Volker A1 - Zivkovic, Miroslav A1 - Belloum, Adam A1 - Bubak, Marian T1 - New approach to allocation planning of many‐task workflows on clouds JF - Concurrency and Computation: Practice and Experience N2 - Experience has shown that a priori created static resource allocation plans are vulnerable to runtime deviations and hence often become uneconomic or highly exceed a predefined soft deadline. The assumption of constant task execution times during allocation planning is even more unlikely in a cloud environment where virtualized resources vary in performance. Revising the initially created resource allocation plan at runtime allows the scheduler to react on deviations between planning and execution. Such an adaptive rescheduling of a many-task application workflow is only feasible, when the planning time can be handled efficiently at runtime. In this paper, we present the static low-complexity resource allocation planning algorithm (LCP) applicable to efficiently schedule many-task scientific application workflows on cloud resources of different capabilities. The benefits of the presented algorithm are benchmarked against alternative approaches. The benchmark results show that LCP is not only able to compete against higher complexity algorithms in terms of planned costs and planned makespan but also outperforms them significantly by magnitudes of 2 to 160 in terms of required planning time. Hence, LCP is superior in terms of practical usability where low planning time is essential such as in our targeted online rescheduling scenario. Y1 - 2020 U6 - http://dx.doi.org/10.1002/cpe.5404 SN - 1532-0634 VL - 32 IS - 2 Article e5404 SP - 1 EP - 16 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Kodomskoi, Leonid A1 - Kotliar, Konstantin A1 - Schröder, Andreas A1 - Weiss, Michael A1 - Hille, Konrad T1 - Suture-Probe Canaloplasty as an Alternative to Canaloplasty using the iTrack™ Microcatheter JF - Journal of Glaucoma Y1 - 2019 U6 - http://dx.doi.org/10.1097/IJG.0000000000001321 SN - 1057-0829 IS - Epub ahead of print PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Schopp, Christoph A1 - Britun, Nikolay A1 - Vorac, Jan A1 - Synek, Petr A1 - Snyders, Rony A1 - Heuermann, Holger T1 - Thermal and Optical Study on the Frequency Dependence of an Atmospheric Microwave Argon Plasma Jet JF - IEEE Transactions on Plasma Science Y1 - 2019 SN - 1939-9375 VL - 47 IS - 7 SP - 3176 EP - 3181 PB - IEEE CY - New York ER - TY - JOUR A1 - Reger, Vitali A1 - Kuhnhenne, Markus A1 - Hachul, Helmut A1 - Döring, Bernd A1 - Blanke, Tobias A1 - Göttsche, Joachim T1 - Plusenergiegebäude 2.0 in Stahlleichtbauweise JF - Stahlbau Y1 - 2019 U6 - http://dx.doi.org/10.1002/stab.201900034 SN - 1437-1049 (E-journal), 0038-9145 (print) VL - 88 IS - 6 SP - 522 EP - 528 PB - Ernst & Sohn CY - Berlin ER - TY - JOUR A1 - Kopp, Alexander A1 - Schmeets, Ralf A1 - Gosau, Martin A1 - Friedrich, Reinhard E. A1 - Fuest, Sandra A1 - Behbahani, Mehdi A1 - Barbeck, Mike A1 - Rutkowski, Rico A1 - Burg, Simon A1 - Kluwe, Lan A1 - Henningsen, Anders T1 - Production and Characterization of Porous Fibroin Scaffolds for Regenerative Medical Application JF - In Vivo Y1 - 2019 U6 - http://dx.doi.org/10.21873/invivo.11536 SN - 1791-7549 VL - 33 IS - 3 SP - 757 EP - 762 ER - TY - JOUR A1 - Stulpe, Werner T1 - Aspects of the Quantum-Classical Connection Based on Statistical Maps JF - Foundations of Physics Y1 - 2019 U6 - http://dx.doi.org/10.1007/s10701-019-00269-9 VL - 49 IS - 6 SP - 677 EP - 692 PB - Springer CY - Berlin ER - TY - JOUR A1 - Engel, Mareike A1 - Bayer, Hendrik A1 - Holtmann, Dirk A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Flavin secretion of Clostridium acetobutylicum in a bioelectrochemical system - Is an iron limitation involved? JF - Bioelectrochemistry Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bioelechem.2019.05.014 SN - 1567-5394 IS - In Press, Accepted Manuscript PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Claer, Mario A1 - Ferrein, Alexander A1 - Schiffer, Stefan T1 - Calibration of a Rotating or Revolving Platform with a LiDAR Sensor JF - Applied Sciences Y1 - 2019 U6 - http://dx.doi.org/10.3390/app9112238 SN - 2076-3417 VL - Volume 9 IS - issue 11, 2238 PB - MDPI CY - Basel ER - TY - JOUR A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - Combinatorial assembly of ferredoxin‐linked modules in Escherichia coli yields a testing platform for Rnf‐complexes JF - Biotechnology and Bioengineering Y1 - 2019 U6 - http://dx.doi.org/10.1002/bit.27079 IS - accepted article SP - 1 EP - 36 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Kapelyukh, Yury A1 - Henderson, Colin James A1 - Scheer, Nico A1 - Rode, Anja A1 - Wolf, Charles Roland T1 - Defining the contribution of CYP1A1 and CYP1A2 to drug metabolism using humanized CYP1A1/1A2 and Cyp1a1/Cyp1a2 KO mice JF - Drug Metabolism and Disposition Y1 - 2019 U6 - http://dx.doi.org/10.1124/dmd.119.087718 IS - Early view ER - TY - JOUR A1 - Jochim, Haldor E. A1 - Menzel, Christoph J. T1 - Die Trassenbündelung als Planungsmethode nachhaltiger Verkehrspolitik JF - Der Eisenbahningenieur : EI Y1 - 2018 SN - 0013-2810 VL - 69 IS - 11 SP - 26 EP - 31 PB - DVV Media Group CY - Hamburg ER - TY - JOUR A1 - Poghossian, Arshak A1 - Geissler, Hanno A1 - Schöning, Michael Josef T1 - Rapid methods and sensors for milk quality monitoring and spoilage detection JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.04.040 SN - 0956-5663 VL - 140 IS - Article 111272 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Cornelis, Peter A1 - Givanoudi, Stella A1 - Yongabi, Derick A1 - Iken, Heiko A1 - Duwé, Sam A1 - Deschaume, Olivier A1 - Robbens, Johan A1 - Dedecker, Peter A1 - Bartic, Carmen A1 - Wübbenhorst, Michael A1 - Schöning, Michael Josef A1 - Heyndrickx, Marc A1 - Wagner, Patrick T1 - Sensitive and specific detection of E. coli using biomimetic receptors in combination with a modified heat-transfer method JF - Biosensors and Bioelectronics Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.bios.2019.04.026 SN - 0956-5663 VL - 136 SP - 97 EP - 105 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Meyer, Carolin A1 - Gaalen, Kerstin van A1 - Leschinger, Tim A1 - Scheyerer, Max J. A1 - Neiss, Wolfram F. A1 - Staat, Manfred A1 - Müller, Lars P. A1 - Wegmann, Kilian T1 - Kyphoplasty of Osteoporotic Fractured Vertebrae: A Finite Element Analysis about Two Types of Cement JF - BioMed Research International Y1 - 2019 U6 - http://dx.doi.org/10.1155/2019/9232813 SP - Article ID 9232813 ER - TY - JOUR A1 - Puppe, Michael A1 - Giuliano, Stefano A1 - Frantz, Cathy A1 - Uhlig, Ralf A1 - Schumacher, Ralph A1 - Ibraheem, Wagdi A1 - Schmalz, Stefan A1 - Waldmann, Barbara A1 - Guder, Christoph A1 - Peter, Dennis A1 - Schwager, Christian A1 - Teixeira Boura, Cristiano José A1 - Alexopoulos, Spiros A1 - Spiegel, Michael A1 - Wortmann, Jürgen A1 - Hinrichs, Matthias A1 - Engelhard, Manfred A1 - Aust, Michael T1 - Techno-economic optimization of molten salt solar tower plants JF - AIP Conference Proceedings art.no. 040033 N2 - In this paper the results of a techno-economic analysis of improved and optimized molten salt solar tower plants (MSSTP plants) are presented. The potential improvements that were analyzed include different receiver designs, different designs of the HTF-system and plant control, increased molten salt temperatures (up to 640°C) and multi-tower systems. Detailed technological and economic models of the solar field, solar receiver and high temperature fluid system (HTF-system) were developed and used to find potential improvements compared to a reference plant based on Solar Two technology and up-to-date cost estimations. The annual yield model calculates the annual outputs and the LCOE of all variants. An improved external tubular receiver and improved HTF-system achieves a significant decrease of LCOE compared to the reference. This is caused by lower receiver cost as well as improvements of the HTF-system and plant operation strategy, significantly reducing the plant own consumption. A novel star receiver shows potential for further cost decrease. The cavity receiver concepts result in higher LCOE due to their high investment cost, despite achieving higher efficiencies. Increased molten salt temperatures seem possible with an adapted, closed loop HTF-system and achieve comparable results to the original improved system (with 565°C) under the given boundary conditions. In this analysis all multi tower systems show lower economic viability compared to single tower systems, caused by high additional cost for piping connections and higher cost of the receivers. REFERENCES Y1 - 2019 U6 - http://dx.doi.org/10.1063/1.5067069 VL - 2033 IS - Issue 1 PB - AIP Publishing CY - Melville, NY ER - TY - JOUR A1 - Tran, Ngoc Trinh A1 - Staat, Manfred T1 - Direct plastic structural design under lognormally distributed strength by chance constrained programming JF - Optimization and Engineering N2 - We propose the so-called chance constrained programming model of stochastic programming theory to analyze limit and shakedown loads of structures under random strength with a lognormal distribution. A dual chance constrained programming algorithm is developed to calculate simultaneously both the upper and lower bounds of the plastic collapse limit and the shakedown limit. The edge-based smoothed finite element method (ES-FEM) is used with three-node linear triangular elements. Y1 - 2020 U6 - http://dx.doi.org/10.1007/s11081-019-09437-2 SN - 1573-2924 VL - 21 IS - 1 SP - 131 EP - 157 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Albanna, Walid A1 - Lüke, Jan Niklas A1 - Schubert, Gerrit Alexander A1 - Dibué-Adjei, Maxine A1 - Kotliar, Konstantin A1 - Hescheler, Jürgen A1 - Clusmann, Hans A1 - Steiger, Hans-Jakob A1 - Hänggi, Daniel A1 - Kamp, Marcel A. A1 - Schneider, Toni A1 - Neumaier, Felix T1 - Modulation of Ca v 2.3 channels by unconjugated bilirubin (UCB) – Candidate mechanism for UCB-induced neuromodulation and neurotoxicity JF - Molecular and Cellular Neuroscience Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.mcn.2019.03.003 SN - 1044-7431 VL - 96 IS - 4 SP - 35 EP - 46 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Rietsch, Stefan H. G. A1 - Brunheim, Sascha A1 - Orzada, Stephan A1 - Voelker, Maximilian N. A1 - Maderwald, Stefan A1 - Bitz, Andreas A1 - Gratz, Marcel A1 - Ladd, Mark E. A1 - Quick, Harald H. T1 - Development and evaluation of a 16-channel receive-only RF coil to improve 7T ultra-high field body MRI with focus on the spine JF - Magnetic Resonance in Medicine Y1 - 2019 U6 - http://dx.doi.org/10.1002/mrm.27731 SN - 1522-2594 IS - Early view PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Lempiäinen, Harri A1 - Couttet, Philippe A1 - Bolognani, Federico A1 - Müller, Arne A1 - Dubost, Valérie A1 - Luisier, Raphaëlle A1 - Rio-Espinola, Alberto del A1 - Vitry, Veronique A1 - Unterberger, Elif B. A1 - Thomson, John P. A1 - Treindl, Fridolin A1 - Metzger, Ute A1 - Wrzodek, Clemens A1 - Hahne, Florian A1 - Zollinger, Tulipan A1 - Brasa, Sarah A1 - Kalteis, Magdalena A1 - Marcellin, Magali A1 - Giudicelli, Fanny A1 - Braeuning, Albert A1 - Morawiec, Laurent A1 - Zamurovic, Natasa A1 - Längle, Ulrich A1 - Scheer, Nico A1 - Schübeler, Dirk A1 - Goodman, Jay A1 - Chibout, Salah-Dine A1 - Marlowe, Jennifer A1 - Theil, Dietlinde A1 - Heard, David J. A1 - Grenet, Olivier A1 - Zell, Andreas A1 - Templin, Markus F. A1 - Meehan, Richard R. A1 - Wolf, Roland C. A1 - Elcombe, Clifford R. A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Rémi A1 - Moggs, Jonathan G. T1 - Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion JF - Toxicological Sciences N2 - The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds. Y1 - 2012 U6 - http://dx.doi.org/10.1093/toxsci/kfs303 SN - 1094-2025 VL - 131 IS - 2 SP - 375 EP - 386 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Morais, Paulo V. A1 - Silva, Anielle C. A. A1 - Dantas, Noelio O. A1 - Schöning, Michael Josef A1 - Siqueira, José R., Jr. T1 - Hybrid Layer‐by‐Layer Film of Polyelectrolytes‐Embedded Catalytic CoFe2O4 Nanocrystals as Sensing Units in Capacitive Electrolyte‐Insulator‐Semiconductor Devices JF - physica status solidi a : applications and materials sciences Y1 - 2019 U6 - http://dx.doi.org/10.1002/pssa.201900044 VL - 216 IS - 1900044 SP - 1 EP - 9 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Nuclear Receptors which play a pivotal role in drug disposition and chemical toxicity JF - Drug Metabolism Reviews Y1 - 2006 U6 - http://dx.doi.org/10.1080/03602530600786232 SN - 1097-9883 VL - 38 IS - 3 SP - 515 EP - 597 ER - TY - JOUR A1 - Stanley, Lesley A. A1 - Horsburgh, Brian C. A1 - Ross, Jillian A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Drug transporters: Gatekeepers controlling access of xenobiotics to the cellular interior JF - Drug Metabolism Reviews Y1 - 2009 U6 - http://dx.doi.org/10.1080/03602530802605040 SN - 1097-9883 VL - 41 IS - 1 SP - 27 EP - 65 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Henderson, Colin J. A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Advances in the generation of mouse models to elucidate the pathways of drug metabolism in rodents and man JF - Expert Review of Clinical Pharmacology Y1 - 2009 U6 - http://dx.doi.org/10.1586/17512433.2.2.105 SN - 1751-2441 VL - 2 IS - 2 SP - 105 EP - 109 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - http://dx.doi.org/10.3109/03602532.2012.738687 SN - 1097-9883 IS - 1 SP - 110 EP - 121 PB - Taylor & Francis CY - London 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 - TY - JOUR A1 - Scheer, Nico A1 - Wilson, Ian D. T1 - A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity JF - Drug Discovery Today N2 - Mice that have been genetically humanized for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging and promising in vivo models for an improved prediction of the pharmacokinetic, drug–drug interaction and safety characteristics of compounds in humans. The specific advantages and disadvantages of these models should be carefully considered when using them for studies in drug discovery and development. Here, an overview on the corresponding genetically humanized and chimeric liver humanized mouse models described to date is provided and illustrated with examples of their utility in drug metabolism and toxicity studies. We compare the strength and weaknesses of the two different approaches, give guidance for the selection of the appropriate model for various applications and discuss future trends and perspectives. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.drudis.2015.09.002 SN - 1359-6446 VL - 21 IS - 2 SP - 250 EP - 263 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Campos-Ortega, José A. T1 - Use of the Gal4-UAS technique for targeted gene expression in the zebrafish JF - Mechanism of Development Y1 - 1999 U6 - http://dx.doi.org/10.1016/S0925-4773(98)00209-3 SN - 0925-4773 VL - 80 IS - 2 SP - 153 EP - 158 ER - TY - JOUR A1 - Halbach, Thorsten A1 - Scheer, Nico T1 - Transcriptional activation by the PHD finger is inhibited through an adjacent leucine zipper that binds 14-3-3 proteins JF - Nucleic Acids Research Y1 - 2000 U6 - http://dx.doi.org/10.1093/nar/28.18.3542 SN - 1362-4962 VL - 28 IS - 18 SP - 3542 EP - 3550 ER - TY - JOUR A1 - Scheer, Nico A1 - Groth, Anne A1 - Hans, Stefan A1 - Campos-Ortega, José A. T1 - An instructive function for Notch in promoting gliogenesis in the zebrafish retina JF - Development Y1 - 2001 SN - 0950-1991 VL - 128 IS - 7 SP - 1099 EP - 1107 ER - TY - JOUR A1 - Lawson, Nathan D. A1 - Scheer, Nico A1 - Pham, Van N. A1 - Kim, Ceol-Hee A1 - Chitnis, Ajay B. A1 - Campos-Ortega, José A. A1 - Weinstein, Brant M. T1 - Notch signaling is required for arterial-venous differentiation during embryonic vascular development JF - Development Y1 - 2001 SN - 1477-9129 VL - 128 IS - 19 SP - 3675 EP - 3683 ER - TY - JOUR A1 - Scheer, Nico A1 - Riedl, Iris A1 - Warren, J.T. A1 - Kuwada, John Y. A1 - Campos-Ortega, José A. T1 - A quantitative analysis of the kinetics of Gal4 activator and effector gene expression in the zebrafish JF - Mechanism of Development Y1 - 2002 U6 - http://dx.doi.org/10.1016/S0925-4773(01)00621-9 SN - 0925-4773 VL - 112 IS - 1-2 SP - 9 EP - 14 ER - TY - JOUR A1 - Hans, Stefan A1 - Scheer, Nico A1 - Riedl, Iris A1 - Weizäcker, Elisabeth von A1 - Blader, Patrick A1 - Campos-Ortega, José A. T1 - her3, a zebrafish member of the hairy-E(spl) family, is repressed by Notch signalling JF - Development Y1 - 2004 U6 - http://dx.doi.org/10.1242/dev.01167 SN - 1477-9129 VL - 131 IS - 12 SP - 2957 EP - 2969 ER - TY - JOUR A1 - Reugels, Alexander M. A1 - Boggetti, Barbara A1 - Scheer, Nico A1 - Campos-Ortega, José A. T1 - Asymmetric localization of Numb:EGFP in dividing neuroepithelial cells during neurulation in Danio rerio JF - Developmental Dynamics Y1 - 2006 U6 - http://dx.doi.org/10.1002/dvdy.20699 SN - 1097-0177 VL - 235 IS - 4 SP - 934 EP - 948 ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - McEwan, Jillian A1 - Beuger, Vincent A1 - Stanley, Lesley A. A1 - Rode, Anja A1 - Wolf, C. Roland T1 - Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines JF - Molecular Pharmacology N2 - The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.111.075192 SN - 1521-0111 VL - 81 IS - 1 SP - 63 EP - 72 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Rode, Anja A1 - Zevnik, Branko A1 - Niehaves, Sandra A1 - Faust, Nicole A1 - Wolf, C. Roland T1 - A novel panel of mouse models to evaluate the role of human pregnane X receptor and constitutive androstane receptor in drug response JF - Journal of Clinical Investigation Y1 - 2008 U6 - http://dx.doi.org/https://doi.org/10.1172/JCI35483 SN - 1558-8238 VL - 118 IS - 9 SP - 3228 EP - 3239 ER - TY - JOUR A1 - Scheer, Nico A1 - Ross, Jillian A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Wolf, C. Roland T1 - In vivo responses of the human and murine pregnane X receptor to dexamethasone in mice JF - Drug Metabolism and Disposition N2 - Dexamethasone (DEX) is a potent and widely used anti-inflammatory and immunosuppressant glucocorticoid. It can bind and activate the pregnane X receptor (PXR), which plays a critical role as xenobiotic sensor in mammals to induce the expression of many enzymes, including cytochromes P450 in the CYP3A family. This induction results in its own metabolism. We have used a series of transgenic mouse lines, including a novel, improved humanized PXR line, to compare the induction profile of PXR-regulated drug-metabolizing enzymes after DEX administration, as well as looking at hepatic responses to rifampicin (RIF). The new humanized PXR model has uncovered further intriguing differences between the human and mouse receptors in that RIF only induced Cyp2b10 in the new humanized model. DEX was found to be a much more potent inducer of Cyp3a proteins in wild-type mice than in mice humanized for PXR. To assess whether PXR is involved in the detoxification of DEX in the liver, we analyzed the consequences of high doses of the glucocorticoid on hepatotoxicity on different PXR genetic backgrounds. We also studied these effects in an additional mouse model in which functional mouse Cyp3a genes have been deleted. These strains exhibited different sensitivities to DEX, indicating a protective role of the PXR and CYP3A proteins against the hepatotoxicity of this compound. Y1 - 2010 U6 - http://dx.doi.org/10.1124/dmd.109.031872 SN - 1521-009X VL - 38 IS - 7 SP - 1046 EP - 1053 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Ross, Jillian A1 - Plummer, Simon M. A1 - Rode, Anja A1 - Scheer, Nico A1 - Bower, Conrad C. A1 - Vogel, Ortwin A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Elcombe, Clifford R. T1 - Human constitutive androstane receptor (CAR) and pregnane X receptor (PXR) support the hypertrophic but not the hyperplastic response to the murine nongenotoxic hepatocarcinogens phenobarbital and chlordane in vivo JF - Toxicological Sciences N2 - Mouse nongenotoxic hepatocarcinogens phenobarbital (PB) and chlordane induce hepatomegaly characterized by hypertrophy and hyperplasia. Increased cell proliferation is implicated in the mechanism of tumor induction. The relevance of these tumors to human health is unclear. The xenoreceptors, constitutive androstane receptors (CARs), and pregnane X receptor (PXR) play key roles in these processes. Novel “humanized” and knockout models for both receptors were developed to investigate potential species differences in hepatomegaly. The effects of PB (80 mg/kg/4 days) and chlordane (10 mg/kg/4 days) were investigated in double humanized PXR and CAR (huPXR/huCAR), double knockout PXR and CAR (PXRKO/CARKO), and wild-type (WT) C57BL/6J mice. In WT mice, both compounds caused increased liver weight, hepatocellular hypertrophy, and cell proliferation. Both compounds caused alterations to a number of cell cycle genes consistent with induction of cell proliferation in WT mice. However, these gene expression changes did not occur in PXRKO/CARKO or huPXR/huCAR mice. Liver hypertrophy without hyperplasia was demonstrated in the huPXR/huCAR animals in response to both compounds. Induction of the CAR and PXR target genes, Cyp2b10 and Cyp3a11, was observed in both WT and huPXR/huCAR mouse lines following treatment with PB or chlordane. In the PXRKO/CARKO mice, neither liver growth nor induction of Cyp2b10 and Cyp3a11 was seen following PB or chlordane treatment, indicating that these effects are CAR/PXR dependent. These data suggest that the human receptors are able to support the chemically induced hypertrophic responses but not the hyperplastic (cell proliferation) responses. At this time, we cannot be certain that hCAR and hPXR when expressed in the mouse can function exactly as the genes do when they are expressed in human cells. However, all parameters investigated to date suggest that much of their functionality is maintained. Y1 - 2010 U6 - http://dx.doi.org/10.1093/toxsci/kfq118 SN - 1096-0929 VL - 116 IS - 2 SP - 452 EP - 466 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Buechel, Sandra A1 - Wolf, C. Roland T1 - Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines JF - Molecular Pharmacology N2 - 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. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.112.080036 SN - 1521-0111 VL - 82 IS - 6 SP - 1022 EP - 1029 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Balimane, Praveen A1 - Hayward, Michael D. A1 - Buechel, Sandra A1 - Kauselmann, Gunther A1 - Wolf, C. Roland T1 - Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line JF - Drug Metabolism and Disposition N2 - 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. Y1 - 2012 U6 - http://dx.doi.org/10.1124/dmd.112.047605 SN - 1521-0111 VL - 40 IS - 11 SP - 2212 EP - 2218 PB - ASPET CY - Bethesda, Md. 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 -