TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Sieker, Tim A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnologie und Bioverfahrenstechnik – Vom ersten Ullmanns Artikel bis hin zu aktuellen Forschungsthemen JF - Chemie Ingenieur Technik N2 - Biotechnologie und die mit ihr verbundenen technischen Prozesse prägen seit Jahrtausenden die Entwicklung der Menschheit. Ausgehend von empirischen Verfahren, insbesondere zur Herstellung von Lebensmitteln und täglichen Gebrauchsgütern, haben sich diese Disziplinen zu einem der innovativsten Zukunftsfelder entwickelt. Durch das immer detailliertere Verständnis zellulärer Vorgänge können mittlerweile Produktionsstämme gezielt optimiert werden. Im Zusammenspiel mit moderner Prozesstechnik können so eine Vielzahl von Bulk- und Feinchemikalien sowie Pharmazeutika effizient hergestellt werden. In diesem Artikel werden exemplarisch einige der aktuellen Trends vorgestellt. Y1 - 2014 U6 - http://dx.doi.org/10.1002/cite.201400083 SN - 0009-286X VL - 86 IS - 12 SP - 2215 EP - 2225 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Wiesen, Sebastian A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Nils A1 - Ulber, Roland T1 - Adsorptive Vorbehandlung von Rohglycerin für die 1,3-Propandiol Fermentation mit Clostridium diolis JF - Chemie Ingenieur Technik N2 - Bei der Gewinnung von Fettsäuren aus Pflanzenölen, z. B. zur Herstellung von Biopolymeren, oder bei der Biodiesel- und Seifenproduktion, fällt Glycerin als Nebenprodukt an. Bei der Biokonversion dieses Rohstoffes zu 1,3-Propandiol wird der Produktionsorganismus Clostridium diolis durch Verunreinigungen im Rohglycerin gehemmt. Als inhibierende Substanzen konnten freie Fettsäuren identifiziert werden. Mithilfe eines adsorptiven Aufarbeitungsverfahrens ist es gelungen, die Fettsäuren zu entfernen und die Konversionseffizienz zu 1,3-Propandiol zu erhöhen. Y1 - 2014 U6 - http://dx.doi.org/10.1002/cite.201300080 N1 - Englischer Titel: Adsorptive Pretreatment of Crude Glycerol Prior to Fermentation to 1,3-Propanediole by Clostridium Diolis VL - 86 IS - 1-2 SP - 129 EP - 135 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Duwe, Anna-Maria A1 - Wiesen, Sebastian A1 - Sieker, Tim A1 - Ulber, Roland T1 - Enzymatic hydrolysis of beech wood lignocellulose at high solid contents and its utilization as substrate for the production of biobutanol and dicarboxylic acids JF - Bioresource Technology N2 - The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.biortech.2014.06.052 VL - 167 SP - 447 EP - 455 PB - Elsevier CY - Amsterdam ER - TY - PAT A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Vorrichtung und Verfahren zur Bestimmung des Kontaktwinkels eines flüssigen oder mit Flüssigkeit gefüllten Körpers [Offenlegungsschrift] N2 - Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Bestimmung des Kontaktwinkels eines flüssigen oder mit Flüssigkeit gefüllten Körpers. Dieser besteht aus einem Träger (1) und einer damit verbundenen, in einem Winkelbereich von mehr als 0° bis maximal 90° neigbaren Ebene (8) mit einer darin ausgebildeten Abrollbahn (9) für den flüssigen oder mit Flüssigkeit gefüllten Körper. An der Ebene (8) sind mehrere Sensoren (11, 12) zur Erfassung der Rolldauer des Körpers entlang der Rollstrecke angeordnet. Erfindungsgemäß ist vorgesehen, dass die Einstellung des Neigungswinkels der Ebene (8) über ein Winkelmessgerät (10) erfolgt, wodurch ein Abrollwinkel erfassbar ist, bei dem der Körper in Bewegung gerät. Aus der Rolldauer, der Rollstrecke und dem Abrollwinkel wird der Kontaktwinkel des Körpers ermittelt. Y1 - 2014 PB - Deutsches Patent- und Markenamt CY - München ER - TY - JOUR A1 - Hoehr, Cornelia A1 - Paulßen, Elisabeth A1 - Benard, Francois A1 - Lee, Chris Jaeil A1 - Hou, Xinchi A1 - Badesso, Brian A1 - Ferguson, Simon A1 - Miao, Qing A1 - Yang, Hua A1 - Buckley, Ken A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Ruth, Thomas A1 - Celler, Anna A1 - Schaffer, Paul T1 - ⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron JF - Nuclear medicine and biology N2 - Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2013.12.016 SN - 1872-9614 VL - 41 IS - 5 SP - 401 EP - 406 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Al-Kaidy, H. A1 - Ulber, R. A1 - Tippkötter, Nils T1 - A platform technology for the automated reaction control in magnetizable micro-fluidic droplets T2 - Biomaterials - made in bioreactors : book of abstracts, May 26 - 28, 2014, Radisson Blu Park Hotel and Conference Dentre, Radebeul, Germany Y1 - 2014 SP - 21 EP - 22 PB - DECHEMA CY - Frankfurt am Main 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 - http://dx.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 - http://dx.doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Mclaughlin, Lesley A. A1 - Rode, Anja A1 - MacLeod, Alastair Kenneth A1 - Henderson, Colin J. A1 - Wolf, Roland C. T1 - Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism JF - Drug Metabolism and Disposition N2 - In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057885 SN - 1521-009X VL - 42 IS - 6 SP - 1022 EP - 1030 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - http://dx.doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils T1 - Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers JF - Journal of Applied Polymer Science N2 - Recently, we have suggested a nanomechanical model for dissipative loss in filled elastomer networks in the context of the Payne effect. The mechanism is based on a total interfiller particle force exhibiting an intermittent loop, due to the combination of short-range repulsion and dispersion forces with a long-range elastic attraction. The sum of these forces leads, under external strain, to a spontaneous instability of “bonds” between the aggregates in a filler network and attendant energy dissipation. Here, we use molecular dynamics simulations to obtain chemically realistic forces between surface modified silica particles. The latter are combined with the above model to estimate the loss modulus and the low strain storage modulus in elastomers containing the aforementioned filler-compatibilizer systems. The model is compared to experimental dynamic moduli of silica filled rubbers. We find good agreement between the model predictions and the experiments as function of the compatibilizer's molecular structure and its bulk concentration. KW - theory and modeling KW - supramolecular structures KW - rubber KW - mechanical properties KW - elastomers Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40806 SN - 1097-4628 VL - 131 IS - 18 SP - 1 EP - 9 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Schroeter, Rebecca A1 - Hoffmann, Tamara A1 - Voigt, Birgit A1 - Meyer, Hanna A1 - Bleisteiner, Monika A1 - Muntel, Jan A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Lalk, Michael A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Putzer, Harald A1 - Hecker, Michael A1 - Schweder, Thomas A1 - Bremer, Erhard T1 - Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges JF - PLoS ONE N2 - The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0080956 SN - 1932-6203 VL - 8 IS - 11 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Handtke, Stefan A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Methling, Karen A1 - Schlüter, Rabea A1 - Albrecht, Dirk A1 - Hijum, Sacha A. F. T. van A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Schweder, Thomas A1 - Hecker, Michael A1 - Voigt, Birgit T1 - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress JF - PLOS one N2 - Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0085625 SN - 1932-6203 VL - 9 IS - 1 PB - PLOS CY - San Francisco ER - TY - CHAP A1 - Frotscher, Ralf A1 - Goßmann, Matthias A1 - Raatschen, Hans-Jürgen A1 - Temiz Artmann, Aysegül A1 - Staat, Manfred T1 - Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM T2 - Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45) N2 - We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments. Y1 - 2015 SN - 978-3-319-02534-6 ; 978-3-319-02535-3 SP - 187 EP - 212 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Seifarth, Volker A1 - Goßmann, Matthias A1 - Grosse, J. O. A1 - Becker, C. A1 - Heschel, I. A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds JF - Urologia Internationalis Y1 - 2015 U6 - http://dx.doi.org/10.1159/000368419 SN - 0042-1138 VL - 2015 IS - 95 SP - 106 EP - 113 PB - Karger CY - Basel ER - TY - JOUR A1 - Kusch, Peter A1 - Rieser, Claudia A1 - Knupp, Gerd A1 - Mang, Thomas T1 - Characterization of copolymers of methacrylic acid with poly(ethylene glycol) methyl ether methacrylate macromonomers by analytical pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) JF - Journal of Analytical and Applied Pyrolysis Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.jaap.2015.03.003 SN - 0165-2370 VL - Vol. 113 SP - 412 EP - 418 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Iken, Heiko A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Development of a multi‐parameter sensor chip for the simultaneous detection of organic compounds in biogas processes JF - Physica status solidi (a) N2 - An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431894 SN - 1862-6319 VL - 212 IS - 6 SP - 1306 EP - 1312 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Kirschbaum, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide JF - Physica status solidi (a) N2 - Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431944 SN - 1862-6319 VL - 212 IS - 6 SP - 1368 EP - 1374 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro JF - Biotechnology and Bioengineering Y1 - 2015 U6 - http://dx.doi.org/10.1002/bit.25658 SN - 1097-0290 VL - 112 IS - 11 SP - 2360 EP - 2372 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Sievers, Susanne A1 - Becher, Dörte A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Schweder, Thomas A1 - Maurer, Karl-Heinz A1 - Hecker, Michael T1 - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium JF - Proteomics Y1 - 2015 U6 - http://dx.doi.org/10.1002/pmic.201400504 SN - 1615-9861 VL - 15 IS - 15 SP - 2629 EP - 2633 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Molinnus, Denise A1 - Bäcker, Matthias A1 - Siegert, Petra A1 - Willenberg, H. A1 - Poghossian, Arshak A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Detection of Adrenaline Based on Substrate Recycling Amplification JF - Procedia Engineering N2 - An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions has been studied. Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.proeng.2015.08.708 SN - 1877-7058 N1 - Eurosensors 2015 VL - 120 SP - 540 EP - 543 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Mariano, K. A1 - Keusgen, M. A1 - Selmer, Thorsten A1 - Schöning, Michael Josef T1 - Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes JF - Procedia Engineering Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.proeng.2015.08.702 SN - 1877-7058 N1 - Part of special issue "Eurosensors 2015" VL - 120 SP - 532 EP - 535 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Takenaga, Shoko A1 - Schneider, Benno A1 - Erbay, E. A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Schöning, Michael Josef A1 - Wagner, Torsten T1 - Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process JF - Physica status solidi (a) N2 - A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201532053 SN - 1862-6319 VL - 212 IS - 6 SP - 1347 EP - 1352 PB - Wiley CY - Weinheim ER - TY - CHAP A1 - Srivastava, Alok A1 - Knolle, F. A1 - Schnug, E. A1 - Scherer, Ulrich W. T1 - Study of Trace Elements in Water Bodies of the Harz Mts. Region, Germany using Total Reflection X Ray Fluorescence (TXRF) T2 - DAE-BRNS 12th National Symposium on Nuclear and Radiochemistry NUCAR 2015, Feb. 9-13, Mumbai, India, Mumbai, India; 02/2015 Y1 - 2015 SP - 355 EP - 356 ER - TY - CHAP A1 - Srivastava, Alok A1 - Knolle, Friedhart A1 - Hoyler, Friedrich A1 - Scherer, Ulrich W. A1 - Schnug, Ewald T1 - Uranium Toxicity in the State of Punjab in North-Western India T2 - Management of Natural Resources in a Changing Environment N2 - Lately there has been an increasing concern about uranium toxicity in some districts of Punjab State located in the North Western part of India after the publication of a report (Blaurock-Busch et al. 2010) which showed that the concentration of uranium in hair and urine of children suffering from physical deformities, neurological and mental disorder from Malwa region (Fig. 1) of Punjab State was manifold higher than the reference ranges. A train which connects the affected region with the nearby city of Bikaner which has a Cancer Hospital has been nicknamed as Cancer Express due to the frenzy generated on account of uranium related toxicity. Y1 - 2015 SN - 978-3-319-12559-6 U6 - http://dx.doi.org/10.1007/978-3-319-12559-6_21 SP - 271 EP - 275 PB - Springer CY - Cham ER - TY - JOUR A1 - Cehreli, Ruksan A1 - Akpinar, Hale A1 - Temiz Artmann, Aysegül A1 - Sagol, Ozgul T1 - Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis JF - Gastroenterology Research Y1 - 2015 U6 - http://dx.doi.org/10.14740/gr683w SN - 1918-2813 VL - 8 IS - 5 SP - 265 EP - 273 ER - TY - CHAP A1 - Breuer, Lars A1 - Raue, Markus A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications T2 - 12. Dresdner Sensor-Symposium 2015 Y1 - 2015 U6 - http://dx.doi.org/10.5162/12dss2015/P5.8 SP - 206 EP - 209 ER - TY - BOOK A1 - Müller, Bodo A1 - Rath, Walter T1 - Formulierung von Kleb- und Dichtstoffen: das kompetente Lehrbuch für Studium und Praxis Y1 - 2015 SN - 978-3-86630-605-9 PB - Vincentz Network CY - Hannover ET - 3., vollst. überarb. Aufl. ER - TY - BOOK A1 - Lauth, Jakob A1 - Kowalczyk, Jürgen T1 - Thermodynamik : eine Einführung Y1 - 2015 SN - 978-3-662-46228-7 U6 - http://dx.doi.org/10.1007/978-3-662-46229-4 PB - Springer Spektrum CY - Berlin ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Tim, Sieker A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnology and bioprocess engineering – from the first ullmann's article to recent trends JF - ChemBioEng Reviews N2 - For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cben.201500008 VL - 2 IS - 3 SP - 175 EP - 184 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Hruschka, Steffen M. A1 - Ulber, Roland T1 - A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal JF - Journal of Chemical Technology and Biotechnology N2 - BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2% and 40.1%, respectively. The steps were then combined in two different ways: (a) a ‘sequential process’ using the zeolite and A200 in batch processes; and (b) a ‘parallel process’ using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry Y1 - 2015 U6 - http://dx.doi.org/10.1002/jctb.4664 VL - 90 IS - 11 SP - 1999 EP - 2006 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schumann, Christiane A1 - Rogin, Sabine A1 - Schneider, Horst A1 - Tippkötter, Nils A1 - Oster, Jürgen A1 - Kampeis, Percy T1 - Simultane Atline-Quantifizierung von Magnetpartikeln und Mikroorganismen bei einer HGMS-Filtration JF - Chemie Ingenieur Technik N2 - Es wird eine neue Atline-Messmethode vorgestellt, mit der während einer Hochgradienten-Magnetseparation (HGMS)-Filtration eine simultane Quantifizierung von Magnetpartikeln und Mikroorganismen im Filtrat vorgenommen werden kann. Dabei gelingt die Quantifizierung signifikant besser als mit bisher verwendeten Messmethoden. Mit dieser Methode ist es möglich, die Trennleistung einer HGMS-Filtration zu bestimmen und einen Filterdurchbruch durch Konzentrationsanstiege im Bereich einiger µg L−1 von Magnetpartikeln im Filtrat frühzeitig zu detektieren, ohne dass nennenswerte Partikelmengen verloren gehen. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cite.201300158 N1 - Englischer Titel: Simultaneous Atline Quantification of Magnetic Particles and Microorganisms in the HGMS Filtration VL - 87 IS - 1-2 SP - 137 EP - 149 ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Aufarbeitung von Polyphenolen aus Weizen mittels Zeolithen am Beispiel der Ferulasäure JF - Chemie IngenieurTechnik N2 - Aufarbeitung von Polyphenolen aus Weizenmittels Zeolithen am Beispiel der Ferulasa¨ ureAlexander Thiel1, Kai Muffler1, Nils Tippko¨ tter1, Kirstin Suck2, Ulrich Sohling2, Friedrich Ruf3und Roland Ulber1,*DOI: 10.1002/cite.201400031Bei der Ferulasa¨ure handelt es sich um einen Wertstoff, der aus Weizen gewonnen und in der Lebensmittel- und Pharma-industrie eingesetzt werden kann. Der Einsatz von Weizen als nachwachsende Rohstoffquelle ist allerdings nur dann wirt-schaftlich durchfu¨hrbar, wenn eine Prozessintegration in die bestehenden industriellen Verfahren gewa¨hrleistet oder einedirekte Konkurrenz zur Mehl- und Sta¨rkeindustrie vermieden werden kann. In diesem Artikel wird ein Verfahren aufge-zeigt, welches hohe Ausbeuten ermo¨glicht und eine Konkurrenz zu bestehenden Verwertungspfaden vermeidet. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cite.201400031 N1 - Englischer Titel: Downstream Processing of Polyphenols from Wheat by Zeolites using the Example of Ferulic Acid VL - 87 IS - 1-2 SP - 128 EP - 136 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Wiesen, Sebastian A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Adsorption of fatty acids to layered double hydroxides in aqueous systems JF - Adsorption N2 - Due to their anion exchange characteristics, layered double hydroxides (LDHs) are suitable for the detoxification of aqueous, fatty acid containing fermentation substrates. The aim of this study is to examine the adsorption mechanism, using crude glycerol from plant oil esterification as a model system. Changes in the intercalation structure in relation to the amount of fatty acids adsorbed are monitored by X-ray diffraction and infra-red spectroscopy. Additionally, calcination of LDH is investigated in order to increase the binding capacity for fatty acids. Our data propose that, at ambient temperature, fatty acids can be bound to the hydrotalcite by adsorption or in addition by intercalation, depending on fatty acid concentration. The adsorption of fatty acids from crude glycerol shows a BET-like behavior. Above a fatty acid concentration of 3.5 g L−1, intercalation of fatty acids can be shown by the appearance of an increased interlayer spacing. This observation suggests a two phase adsorption process. Calcination of LDHs allows increasing the binding capacity for fatty acids by more than six times, mainly by reduction of structural CO32−. Y1 - 2015 VL - 21 IS - 6-7 SP - 459 EP - 466 PB - Springer CY - Berlin ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Hoehr, Cornelia A1 - Hou, Xinchi A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Adam, Michael J. A1 - Ruth, Thomas J. A1 - Celler, Anna A1 - Buckley, Ken A1 - Benard, Francois A1 - Schaffer, Paul T1 - Production of Y-86 and other radiometals for research purposes using a solution target system JF - Nuclear medicine and biology Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2015.06.005 SN - 1872-9614 VL - 42 IS - 11 SP - 842 EP - 849 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Oswald, Stefan A1 - Busch, Diana A1 - Mclaughlin, Lesley A. A1 - Lin, De A1 - Henderson, Colin J. A1 - Wolf, C. Roland T1 - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065656 SN - 1521-009x VL - 43 IS - 11 SP - 1679 EP - 1690 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Hough, Lindsay B. A1 - Nalwalk, Julia W. A1 - Ding, Xinxin A1 - Scheer, Nico T1 - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065490 SN - 1521-009x VL - 43 IS - 9 SP - 1326 EP - 1330 ER - TY - JOUR A1 - Henderson, Colin J. A1 - Mclaughlin, Lesley A. A1 - Scheer, Nico A1 - Stanley, Lesley A. A1 - Wolf, C. Roland T1 - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s JF - Molecular Pharmacology Y1 - 2015 U6 - http://dx.doi.org/10.1124/mol.114.097394 SN - 1521-0111 VL - 87 IS - 4 SP - 733 EP - 739 PB - ASPET CY - Bethesda ER - TY - CHAP A1 - Wolf, C. Roland A1 - Kapelyukh, Yury A1 - Scheer, Nico A1 - Henderson, Colin J. ED - Wilson, Alan G. E. T1 - Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs N2 - The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic. Y1 - 2015 SN - 978-1-78262-778-4 U6 - http://dx.doi.org/10.1039/9781782622376-00152 SP - 152 EP - 176 PB - RSC Publ. CY - Cambridge ER - TY - JOUR A1 - Hager, Jonathan A1 - Hentschke, Reinhard A1 - Hojdis, Nils A1 - Karimi-Varzaneh, Hossein Ali T1 - Computer Simulation of Particle–Particle Interaction in a Model Polymer Nanocomposite JF - Macromolecules Y1 - 2015 U6 - http://dx.doi.org/10.1021/acs.macromol.5b01864 SN - 1520-5835 VL - 48 IS - 24 SP - 9039 EP - 9049 ER - TY - CHAP A1 - Wulfhorst, Helene A1 - Merseburg, Johannes A1 - Tippkötter, Nils T1 - Analyse von Lignocellulose mittels dynamischer Differenzkalorimetrie und Infrarot – Spektrometrie T2 - 12. Dresdner Sensor-Symposium 2015 2015-12-07 - 2015-12-09 Y1 - 2015 SN - 978-3-9813484-9-1 U6 - http://dx.doi.org/10.5162/12dss2015/P6.2 SP - 210 EP - 215 ER - TY - PAT A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Method for production of single-stranded macronucleotides N2 - The invention relates to a method for production of single-stranded macronucleotides by amplifying and ligating an extended monomeric single-stranded target nucleic acid sequence (targetss) into a repetitive cluster of double-stranded target nucleic acid sequences (targetds), and subsequently cloning the construct into a vector (aptagene vector). The aptagene vector is transformed into host cells for replication of the aptagene and isolated in order to optain single-stranded target sequences (targetss). The invention also relates to single-stranded nucleic acids, produced by a method of the invention. Y1 - 2015 N1 - Patent auch unter EP2774996, EP2774996, US2017145460 und US9944966 veröffentlicht. ER - TY - PAT A1 - Huschyar, Al-Kaidy A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - System und Verfahren zur Durchführung von chemischen, biologischen oder physikalischen Reaktionen Y1 - 2015 N1 - Patent EP2821134A1 ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Strobel, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems JF - Physica status solidi (a) N2 - Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium. Y1 - 2016 U6 - http://dx.doi.org/10.1002/pssa.201533056 SN - 1862-6300 VL - 213 IS - 6 SP - 1520 EP - 1525 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Kasper, Katharina A1 - Schiffels, Johannes A1 - Krafft, Simone A1 - Kuperjans, Isabel A1 - Elbers, Gereon A1 - Selmer, Thorsten T1 - Biogas Production on Demand Regulated by Butyric Acid Addition T2 - IOP Conference Series: Earth and Environmental Science. Bd. 32 Y1 - 2016 U6 - http://dx.doi.org/10.1088/1755-1315/32/1/012009 SN - 1755-1315 N1 - ICARET 2016, International Conference on Advances in Renewable Energy and Technologies, Putrajaya, MY, Feb 23-25, 2016 VL - 32 SP - 012009/1 EP - 012009/4 ER - TY - JOUR A1 - Niedermeyer, Angela A1 - Zhou, Bei A1 - Dursun, Gözde A1 - Temiz Artmann, Aysegül A1 - Markert, Bernd T1 - An examination of tissue engineered scaffolds in a bioreactor JF - Proceedings in Applied Mathematics and Mechanics PAMM N2 - Replacement tissues, designed to fill in articular cartilage defects, should exhibit the same properties as the native material. The aim of this study is to foster the understanding of, firstly, the mechanical behavior of the material itself and, secondly, the influence of cultivation parameters on cell seeded implants as well as on cell migration into acellular implants. In this study, acellular cartilage replacement material is theoretically, numerically and experimentally investigated regarding its viscoelastic properties, where a phenomenological model for practical applications is developed. Furthermore, remodeling and cell migration are investigated. Y1 - 2016 U6 - http://dx.doi.org/10.1002/pamm.201610038 SN - 1617-7061 N1 - Joint Annual Meeting of DMV and GAMM 2016, 87th Annual Meeting of the International Association of Applied Mathematics and Mechanics (GAMM) and Deutsche Mathematiker-Vereinigung (DMV), Braunschweig, DE, Mar 7-11, 2016 VL - 16 IS - 1 SP - 99 EP - 100 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pinkenburg, Olaf A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - Das CoLibry-Konzept – ein Werkzeugkasten für die Synthetische Biologie: Bioproduktion JF - BIOspektrum N2 - Regardless of size or destination, synthetic biology starts with com-parably small information units, which need to be combined and properly arranged in order to achieve a certain goal. This may be the de novo synthesis of individual genes from oligonucleotides, a shuffling of protein domains in order to create novel biocatalysts, the assembly of multiple enzyme encoding genes in metabolic pathway design, or strain development at the production stage. The CoLibry concept has been designed in order to close the gap between recombinant production of individual genes and genome editing. Y1 - 2016 U6 - http://dx.doi.org/10.1007/s12268-016-0734-8 VL - 22 IS - 6 SP - 593 EP - 595 PB - Springer CY - Berlin ER - TY - JOUR A1 - Heinze, D. A1 - Mang, Thomas A1 - Popescu, C. A1 - Weichold, O. T1 - Effect of side chain length and degree of polymerization on the decomposition and crystallization behaviour of chlorinated poly(vinyl ester) oligomers JF - Thermochimica Acta N2 - Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃–(CH₂CH (OCO(CH₂)ₘCH₃))ₙ–Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated. All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.tca.2016.05.015 SN - 0040-6031 (electronic) VL - 637 SP - 143 EP - 153 PB - Elsevier CY - Amsterdam ER - TY - BOOK A1 - Feuerriegel, Uwe T1 - Verfahrenstechnik mit EXCEL: Verfahrenstechnische Berechnungen effektiv durchführen und professionell dokumentieren Y1 - 2016 SN - 978-3-658-02902-9 U6 - http://dx.doi.org/10.1007/978-3-658-02903-6 N1 - 152 Abbildungen, 94 Abbildungen in Farbe Gedruckt in der Bibliothek unter der Signatur: 21 ZNK 11 PB - Springer Fachmedien CY - Wiesbaden ER - TY - BOOK A1 - Lauth, Jakob T1 - Physikalische Chemie, 5: Elektrochemie Y1 - 2016 SN - 978-3-662-47559-1 PB - Springer CY - Berlin ER - TY - BOOK A1 - Lauth, Jakob T1 - Physikalische Chemie, 4: Reaktionskinetik Y1 - 2016 SN - 978-3-662-47674-1 PB - Springer CY - Berlin ER - TY - BOOK A1 - Lauth, Jakob T1 - Physikalische Chemie, 3: Phasengleichgewichte Y1 - 2016 SN - 978-3-662-47571-3 PB - Springer CY - Berlin ER - TY - BOOK A1 - Lauth, Jakob T1 - Physikalische Chemie, 2: Chemische Thermodynamik Y1 - 2016 SN - 978-3-662-47621-5 PB - Springer CY - Berlin ER - TY - BOOK A1 - Lauth, Jakob T1 - Physikalische Chemie, 1: Grundlagen der Thermodynamik und Verhalten der Gase Y1 - 2016 SN - 978-3-662-47676-5 PB - Springer CY - Berlin ER - TY - BOOK A1 - Lauth, Jakob A1 - Kowalczyk, Jürgen T1 - Einführung in die Physik und Chemie der Grenzflächen und Kolloide Y1 - 2016 SN - 978-3-662-47018-3 U6 - http://dx.doi.org/10.1007/978-3-662-47018-3 PB - Springer CY - Berlin ER - TY - JOUR A1 - Molinnus, Denise A1 - Sorich, Maren A1 - Bartz, Alexander A1 - Siegert, Petra A1 - Willenberg, Holger S. A1 - Lisdat, Fred A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate JF - Sensors and Actuators B: Chemical N2 - An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer’s solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.snb.2016.06.064 SN - 0925-4005 VL - 237 SP - 190 EP - 195 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Ghosch, S. A1 - Baier, M. A1 - Schütz, J. A1 - Schneider, Felix A1 - Scherer, Ulrich W. T1 - Analysis of electronic autoradiographs by mathematical post-processing JF - Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology N2 - Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution. Y1 - 2016 U6 - http://dx.doi.org/10.1080/10420150.2016.1155587 SN - 1029-4953 VL - 171 IS - 1-2 SP - 161 EP - 172 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Rösch, C. A1 - Kratz, F. A1 - Hering, T. A1 - Trautmann, S. A1 - Umanskaya, N. A1 - Tippkötter, Nils A1 - Müller-Renno, C.M. A1 - Ulber, R. A1 - Hannig, M. A1 - Ziegler, C. T1 - Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity JF - Colloids and Surfaces B: Biointerfaces N2 - The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.colsurfb.2016.09.048 VL - 149 IS - 1 SP - 115 EP - 121 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Roth, Jasmine A1 - Tippkötter, Nils T1 - Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium JF - Cellulose Chemistry and Technology N2 - Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹. Y1 - 2016 VL - 50 IS - 3-4 SP - 405 EP - 410 PB - Editura Academiei Romane CY - Bukarest ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils T1 - Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase JF - Engineering in Life Sciences N2 - In the field of biotechnology and molecular biology, the use of small liquid volumes has significant advantages. In particular, screening and optimization runs with acceptable amounts of expensive and hardly available catalysts, reagents, or biomolecules are feasible with microfluidic technologies. The presented new microfluidic system is based on the inclusion of small liquid volumes by a protective shell of magnetizable microparticles. Hereby, discrete aqueous microreactor drops with volumes of 1–30 μL can be formed on a simple planar surface. A digital movement and manipulation of the microreactor is performed by overlapping magnetic forces. The magnetic forces are generated by an electrical coil matrix positioned below a glass plate. With the new platform technology, several discrete reaction compartments can be moved simultaneously on one surface. Due to the magnetic fields, the reactors can even be merged to initiate reactions by mixing or positioned above surface-immobilized catalysts and then opened by magnetic force. Comparative synthesis routes of the magnetizable shell particles and superhydrophobic glass slides including their performance and stability with the reaction platform are described. The influence of diffusive mass transport during the catalyzed reaction is discussed by evaluation finite element model of the microreactor. Furthermore, a first model dye reaction of the enzyme laccase has been established. Y1 - 2016 U6 - http://dx.doi.org/10.1002/elsc.201400124 VL - 16 IS - 3 SP - 222 EP - 230 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Tippkötter, Nils ED - Kaltschmidt, Martin T1 - Grundlagen der bio-chemischen Umwandlung T2 - Energie aus Biomasse : Grundlagen, Techniken und Verfahren Y1 - 2016 SN - 978-3-662-47437-2 (Print) SN - 978-3-662-47438-9 (Online) U6 - http://dx.doi.org/10.1007/978-3-662-47438-9 SP - 1447 EP - 1500 PB - Springer Vieweg CY - Berlin ; Heidelberg ET - 3., aktualisierte, erweiterte Auflage ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Kuthan, Kai A1 - Hering, Thomas A1 - Tippkötter, Nils T1 - Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation JF - Journal of Visualized Experiments N2 - For the successful implementation of microfluidic reaction systems, such as PCR and electrophoresis, the movement of small liquid volumes is essential. In conventional lab-on-a-chip-platforms, solvents and samples are passed through defined microfluidic channels with complex flow control installations. The droplet actuation platform presented here is a promising alternative. With it, it is possible to move a liquid drop (microreactor) on a planar surface of a reaction platform (lab-in-a-drop). The actuation of microreactors on the hydrophobic surface of the platform is based on the use of magnetic forces acting on the outer shell of the liquid drops which is made of a thin layer of superhydrophobic magnetite particles. The hydrophobic surface of the platform is needed to avoid any contact between the liquid core and the surface to allow a smooth movement of the microreactor. On the platform, one or more microreactors with volumes of 10 µL can be positioned and moved simultaneously. The platform itself consists of a 3 x 3 matrix of electrical double coils which accommodate either neodymium or iron cores. The magnetic field gradients are automatically controlled. By variation of the magnetic field gradients, the microreactors' magnetic hydrophobic shell can be manipulated automatically to move the microreactor or open the shell reversibly. Reactions of substrates and corresponding enzymes can be initiated by merging the microreactors or bringing them into contact with surface immobilized catalysts. Y1 - 2016 U6 - http://dx.doi.org/10.3791/54643 SN - 1940-087X IS - Issue 126 ER - TY - JOUR A1 - Wulfhorst, Helene A1 - Duwe, Anna-Maria A1 - Merseburg, Johannes A1 - Tippkötter, Nils T1 - Compositional analysis of pretreated (beech) wood using differential scanning calorimetry and multivariate data analysis JF - Tetrahedron N2 - The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.tet.2016.04.029 VL - 72 IS - 46 SP - 7329 EP - 7334 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Engel, M. A1 - Thieringer, J. A1 - Tippkötter, Nils T1 - Microbial electrosynthesis for sustainable biobutanol production T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 77 EP - 78 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Hering, T. A1 - Ulber, Roland A1 - Tippkötter, Nils T1 - Development of a screening system for antimicrobial surfaces T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 129 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Roth, J. A1 - Möhring, S. A1 - Tippkötter, Nils T1 - Characterization and evaluation of lignocellulosic biomass 130 hydrolysates for ABE fermentation T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 130 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Möhring, S. A1 - Wulfhorst, H. A1 - Roth, J. A1 - Tippkötter, Nils T1 - Pretreatment strategies for lignocellulosic biomass T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 131 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Capitain, C. A1 - Hering, T. A1 - Tippkötter, Nils A1 - Ulber, R. T1 - Enzymatic polymerization of lignin model compounds and solubilized lignin in an aqueous ethanol extract T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 151 EP - 152 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Wulfhorst, H. A1 - Duwe, A. A1 - Möhring, S. A1 - Jurca, O. A1 - Tippkötter, Nils T1 - Analysis of pretreated biomass by differential scanning 132 calorimetry and multivariate data analysis T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 132 PB - DECHEMA CY - Frankfurt am Main ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Lengkeek, Nigel A. A1 - Le, Van So A1 - Pellegrini, Paul A. A1 - Greguric, Ivan A1 - Weiner, Ron T1 - The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [⁶⁸Ga(DOTATATE)] JF - Applied Radiation and Isotopes N2 - [⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.apradiso.2015.09.008 SN - 1872-9800 VL - 107 SP - 13 EP - 16 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Infantino, Angelo A1 - Paulßen, Elisabeth A1 - Mostacci, Domiziano A1 - Schaffer, Paul A1 - Trinczek, Michael A1 - Hoehr, Cornelia T1 - Assessment of the production of medical isotopes using the Monte Carlo code FLUKA: Simulations against experimental measurements JF - Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms N2 - The Monte Carlo code FLUKA is used to simulate the production of a number of positron emitting radionuclides, ¹⁸F, ¹³N, ⁹⁴Tc, ⁴⁴Sc, ⁶⁸Ga, ⁸⁶Y, ⁸⁹Zr, ⁵²Mn, ⁶¹Cu and ⁵⁵Co, on a small medical cyclotron with a proton beam energy of 13 MeV. Experimental data collected at the TR13 cyclotron at TRIUMF agree within a factor of 0.6 ± 0.4 with the directly simulated data, except for the production of ⁵⁵Co, where the simulation underestimates the experiment by a factor of 3.4 ± 0.4. The experimental data also agree within a factor of 0.8 ± 0.6 with the convolution of simulated proton fluence and cross sections from literature. Overall, this confirms the applicability of FLUKA to simulate radionuclide production at 13 MeV proton beam energy. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.nimb.2015.10.067 SN - 1872-9584 VL - 366 SP - 117 EP - 123 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Zhang, Jin A1 - Heimbach, Tycho A1 - Scheer, Nico A1 - Barve, Avantika A1 - Li, Wenkui A1 - Lin, Wen A1 - He, Handan T1 - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling JF - Journal of Pharmaceutical Sciences N2 - NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir. Y1 - 2016 U6 - http://dx.doi.org/doi.org/10.1016/j.xphs.2016.01.021 SN - 0022-3549 VL - Volume 105 IS - Issue 4 SP - 1398 EP - 1404 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Dallas, Shannon A1 - Salphati, Laurent A1 - Gomez-Zepeda, David A1 - Wanek, Thomas A1 - Chen, Liangfu A1 - Chu, Xiaoyan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Menet, Marie-Claude A1 - Chasseigneaux, Stephanie A1 - Declèves, Xavier A1 - Langer, Oliver A1 - Pierre, Esaie A1 - DiLoreto, Karen A1 - Hoft, Carolin A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Pereira, Tony A1 - Andonian, Clara A1 - Simic, Damir A1 - Rode, Anja A1 - Yabut, Jocelyn A1 - Zhang, Xiaolin A1 - Scheer, Nico T1 - Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model JF - Molecular Pharmacology N2 - Breast cancer resistance protein (BCRP) is expressed in various tissues, such as the gut, liver, kidney and blood brain barrier (BBB), where it mediates the unidirectional transport of substrates to the apical/luminal side of polarized cells. Thereby BCRP acts as an efflux pump, mediating the elimination or restricting the entry of endogenous compounds or xenobiotics into tissues and it plays important roles in drug disposition, efficacy and safety. Bcrp knockout mice (Bcrp−/−) have been used widely to study the role of this transporter in limiting intestinal absorption and brain penetration of substrate compounds. Here we describe the first generation and characterization of a mouse line humanized for BCRP (hBCRP), in which the mouse coding sequence from the start to stop codon was replaced with the corresponding human genomic region, such that the human transporter is expressed under control of the murine Bcrp promoter. We demonstrate robust human and loss of mouse BCRP/Bcrp mRNA and protein expression in the hBCRP mice and the absence of major compensatory changes in the expression of other genes involved in drug metabolism and disposition. Pharmacokinetic and brain distribution studies with several BCRP probe substrates confirmed the functional activity of the human transporter in these mice. Furthermore, we provide practical examples for the use of hBCRP mice to study drug-drug interactions (DDIs). The hBCRP mouse is a promising model to study the in vivo role of human BCRP in limiting absorption and BBB penetration of substrate compounds and to investigate clinically relevant DDIs involving BCRP. Y1 - 2016 U6 - http://dx.doi.org/10.1124/mol.115.102079 SN - 1521-0111 VL - 89 IS - 5 SP - 492 EP - 504 PB - ASPET CY - Bethesda, Md. 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 - CHAP A1 - Scheer, Nico A1 - Chu, Xiaoyan A1 - Salphati, Laurent A1 - Zamek-Gliszczynski, Maciej J. ED - Nicholls, Glynis T1 - Knockout and humanized animal models to study membrane transporters in drug development T2 - Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development Y1 - 2016 SN - 978-1-78262-379-3 U6 - http://dx.doi.org/10.1039/9781782623793-00298 SP - 298 EP - 332 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Svaneborg, Carsten A1 - Karimi-Varzaneh, Hossein Ali A1 - Hojdis, Nils A1 - Fleck, Franz A1 - Everaers, Ralf T1 - Multiscale approach to equilibrating model polymer melts JF - Physical Review E N2 - We present an effective and simple multiscale method for equilibrating Kremer Grest model polymer melts of varying stiffness. In our approach, we progressively equilibrate the melt structure above the tube scale, inside the tube and finally at the monomeric scale. We make use of models designed to be computationally effective at each scale. Density fluctuations in the melt structure above the tube scale are minimized through a Monte Carlo simulated annealing of a lattice polymer model. Subsequently the melt structure below the tube scale is equilibrated via the Rouse dynamics of a force-capped Kremer-Grest model that allows chains to partially interpenetrate. Finally the Kremer-Grest force field is introduced to freeze the topological state and enforce correct monomer packing. We generate 15 melts of 500 chains of 10.000 beads for varying chain stiffness as well as a number of melts with 1.000 chains of 15.000 monomers. To validate the equilibration process we study the time evolution of bulk, collective, and single-chain observables at the monomeric, mesoscopic, and macroscopic length scales. Extension of the present method to longer, branched, or polydisperse chains, and/or larger system sizes is straightforward. Y1 - 2016 U6 - http://dx.doi.org/10.1103/PhysRevE.94.032502 SN - 2470-0053 VL - 94 IS - 032502 PB - AIP Publishing CY - Melville, NY ER - TY - JOUR A1 - Schwab, Lukas A1 - Hojdis, Nils A1 - Lacayo, Jorge A1 - Wilhelm, Manfred T1 - Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber JF - Macromolecular Materials and Engineering N2 - Rubber materials filled with reinforcing fillers display nonlinear rheological behavior at small strain amplitudes below γ0 < 0.1. Nevertheless, rheological data are analyzed mostly in terms of linear parameters, such as shear moduli (G′, G″), which loose their physical meaning in the nonlinear regime. In this work styrene butadiene rubber filled with carbon black (CB) under large amplitude oscillatory shear (LAOS) is analyzed in terms of the nonlinear parameter I3/1. Three different CB grades are used and the filler load is varied between 0 and 70 phr. It is found that I3/1(φ) is most sensitive to changes of the total accessible filler surface area at low strain amplitudes (γ0 = 0.32). The addition of up to 70 phr CB leads to an increase of I3/1(φ) by a factor of more than ten. The influence of the measurement temperature on I3/1 is pronounced for CB levels above the percolation threshold. Y1 - 2016 U6 - http://dx.doi.org/10.1002/mame.201500356 SN - 1439-2054 VL - 301 IS - 4 SP - 457 EP - 468 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Harish, Ajay B. A1 - Wriggers, Peter A1 - Jungk, Juliane A1 - Hojdis, Nils A1 - Recker, Carla T1 - Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers JF - Computational Mechanics N2 - Elastomers are exceptional materials owing to their ability to undergo large deformations before failure. However, due to their very low stiffness, they are not always suitable for industrial applications. Addition of filler particles provides reinforcing effects and thus enhances the material properties that render them more versatile for applications like tyres etc. However, deformation behavior of filled polymers is accompanied by several nonlinear effects like Mullins and Payne effect. To this day, the physical and chemical changes resulting in such nonlinear effect remain an active area of research. In this work, we develop a heterogeneous (or multiphase) constitutive model at the mesoscale explicitly considering filler particle aggregates, elastomeric matrix and their mechanical interaction through an approximate interface layer. The developed constitutive model is used to demonstrate cluster breakage, also, as one of the possible sources for Mullins effect observed in non-crystallizing filled elastomers. Y1 - 2016 U6 - http://dx.doi.org/10.1007/s00466-015-1251-1 SN - 1432-0924 VL - 57 SP - 653 EP - 677 PB - Springer CY - Berlin ER - TY - PAT A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Vorrichtung und Verfahren zur Bestimmung des Kontaktwinkels eines Flüssigkörpers mit einer Festkörperoberfläche N2 - Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Bestimmung des Kontaktwinkels eines flüssigen oder mit Flüssigkeit gefüllten Körpers. Dieser besteht aus einem Träger (1) und einer damit verbundenen, in einem Winkelbereich von mehr als 0 ° bis maximal 90 ° neigbaren Ebene (8) mit einer darin ausgebildeten Abrollbahn (9) für den flüssigen oder mit Flüssigkeit gefüllten Körper. An der Ebene (8) sind mehrere Sensoren (11,12) zur Erfassung der Rolldauer des Körpers entlang der Rollstrecke angeordnet. Erfindungsgemäß ist vorgesehen, dass die Einstellung des Neigungswinkels der Ebene (8) über ein Winkelmessgerät (10) erfolgt, wodurch ein Abrollwinkel erfassbar ist, bei dem der Körper in Bewegung gerät. Aus der Rolldauer, der Rollstrecke und dem Abrollwinkel wird der Kontaktwinkel des Körpers ermittelt. Y1 - 2016 N1 - Patent auch unter DE102014000419 und WO2015107159 veröffentlicht. ER - TY - JOUR A1 - Muschallik, Lukas A1 - Molinnus, Denise A1 - Bongaerts, Johannes A1 - Pohl, Martina A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Siegert, Petra A1 - Selmer, Thorsten T1 - (R,R)-Butane-2,3-diol Dehydrogenase from Bacillus clausii DSM 8716T: Cloning and Expression of the bdhA-Gene, and Initial Characterization of Enzyme JF - Journal of Biotechnology N2 - The gene encoding a putative (R,R)-butane-2,3-diol dehydrogenase (bdhA) from Bacillus clausii DSM 8716T was isolated, sequenced and expressed in Escherichia coli. The amino acid sequence of the encoded protein is only distantly related to previously studied enzymes (identity 33–43%) and exhibited some uncharted peculiarities. An N-terminally StrepII-tagged enzyme variant was purified and initially characterized. The isolated enzyme catalyzed the (R)-specific oxidation of (R,R)- and meso-butane-2,3-diol to (R)- and (S)-acetoin with specific activities of 12 U/mg and 23 U/mg, respectively. Likewise, racemic acetoin was reduced with a specific activity of up to 115 U/mg yielding a mixture of (R,R)- and meso-butane-2,3-diol, while the enzyme reduced butane-2,3-dione (Vmax 74 U/mg) solely to (R,R)-butane-2,3-diol via (R)-acetoin. For these reactions only activity with the co-substrates NADH/NAD+ was observed. The enzyme accepted a selection of vicinal diketones, α-hydroxy ketones and vicinal diols as alternative substrates. Although the physiological function of the enzyme in B. clausii remains elusive, the data presented herein clearly demonstrates that the encoded enzyme is a genuine (R,R)-butane-2,3-diol dehydrogenase with potential for applications in biocatalysis and sensor development. Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.jbiotec.2017.07.020 SN - 0168-1656 VL - 258 SP - 41 EP - 50 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Röhlen, Desiree A1 - Pilas, Johanna A1 - Schöning, Michael Josef A1 - Selmer, Thorsten T1 - Development of an amperometric biosensor platform for the combined determination of l-Malic, Fumaric, and l-Aspartic acid JF - Applied Biochemistry and Biotechnology N2 - Three amperometric biosensors have been developed for the detection of L-malic acid, fumaric acid, and L -aspartic acid, all based on the combination of a malate-specific dehydrogenase (MDH, EC 1.1.1.37) and diaphorase (DIA, EC 1.8.1.4). The stepwise expansion of the malate platform with the enzymes fumarate hydratase (FH, EC 4.2.1.2) and aspartate ammonia-lyase (ASPA, EC 4.3.1.1) resulted in multi-enzyme reaction cascades and, thus, augmentation of the substrate spectrum of the sensors. Electrochemical measurements were carried out in presence of the cofactor β-nicotinamide adenine dinucleotide (NAD+) and the redox mediator hexacyanoferrate (III) (HCFIII). The amperometric detection is mediated by oxidation of hexacyanoferrate (II) (HCFII) at an applied potential of + 0.3 V vs. Ag/AgCl. For each biosensor, optimum working conditions were defined by adjustment of cofactor concentrations, buffer pH, and immobilization procedure. Under these improved conditions, amperometric responses were linear up to 3.0 mM for L-malate and fumarate, respectively, with a corresponding sensitivity of 0.7 μA mM−1 (L-malate biosensor) and 0.4 μA mM−1 (fumarate biosensor). The L-aspartate detection system displayed a linear range of 1.0–10.0 mM with a sensitivity of 0.09 μA mM−1. The sensor characteristics suggest that the developed platform provides a promising method for the detection and differentiation of the three substrates. Y1 - 2017 U6 - http://dx.doi.org/10.1007/s12010-017-2578-1 SN - 1559-0291 VL - 183 SP - 566 EP - 581 PB - Springer CY - Berlin ER - TY - JOUR A1 - Pilas, Johanna A1 - Yazici, Yasemen A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Optimization of an amperometric biosensor array for simultaneous measurement of ethanol, formate, d- and l-lactate JF - Electrochimica Acta N2 - The immobilization of NAD+-dependent dehydrogenases, in combination with a diaphorase, enables the facile development of multiparametric sensing devices. In this work, an amperometric biosensor array for simultaneous determination of ethanol, formate, d- and l-lactate is presented. Enzyme immobilization on platinum thin-film electrodes was realized by chemical cross-linking with glutaraldehyde. The optimization of the sensor performance was investigated with regard to enzyme loading, glutaraldehyde concentration, pH, cofactor concentration and temperature. Under optimal working conditions (potassium phosphate buffer with pH 7.5, 2.5 mmol L-1 NAD+, 2.0 mmol L-1 ferricyanide, 25 °C and 0.4% glutaraldehyde) the linear working range and sensitivity of the four sensor elements was improved. Simultaneous and cross-talk free measurements of four different metabolic parameters were performed successfully. The reliable analytical performance of the biosensor array was demonstrated by application in a clarified sample of inoculum sludge. Thereby, a promising approach for on-site monitoring of fermentation processes is provided. KW - Simultaneous determination KW - Enzymatic biosensor KW - Diaphorase KW - Dehydrogenase Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.electacta.2017.07.119 SN - 0013-4686 VL - 251 SP - 256 EP - 262 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Seifarth, Volker A1 - Grosse, Joachim O. A1 - Grossmann, Matthias A1 - Janke, Heinz Peter A1 - Arndt, Patrick A1 - Koch, Sabine A1 - Epple, Matthias A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Mechanical induction of bi-directional orientation of primary porcine bladder smooth muscle cells in tubular fibrin-poly(vinylidene fluoride) scaffolds for ureteral and urethral repair using cyclic and focal balloon catheter stimulation JF - Journal of Biomaterials Applications Y1 - 2017 U6 - http://dx.doi.org/10.1177/0885328217723178 SN - 1530-8022 VL - 32 IS - 3 SP - 321 EP - 330 PB - Sage CY - London ER - TY - JOUR A1 - Breuer, Lars A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Investigation of the spatial resolution of a laser-based stimulation process for light-addressable hydrogels with incorporated graphene oxide by means of IR thermography JF - Sensors and Actuators A: Physical Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.sna.2017.11.031 SN - 0924-4247 VL - 268 SP - 126 EP - 132 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Demmer, Julius K. A1 - Chowdhury, Nilanjan Pal A1 - Selmer, Thorsten A1 - Ermler, Ulrich A1 - Buckel, Wolfgang T1 - The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile JF - Nature Communications Y1 - 2017 U6 - http://dx.doi.org/10.1038/s41467-017-01746-3 SN - 2041-1723 N1 - Article number 1577 VL - 8 IS - 1 SP - 1 EP - 10 ER - TY - JOUR A1 - Werkhausen, Amelie A1 - Albracht, Kirsten A1 - Cronin, Neil J. A1 - Meier, Rahel A1 - Mojsen-Moeller, Jens A1 - Seynnes, Olivier R. T1 - Modulation of muscle-tendon interaction in the human triceps surae during an energy dissipation task JF - Journal of Experimental Biology Y1 - 2017 U6 - http://dx.doi.org/10.1242/jeb.164111 SN - 0022-0949 VL - 220 IS - 22 SP - 4141 EP - 4149 ER - TY - JOUR A1 - Liu, Z. A1 - Schaap, K. S. A1 - Ballemans, L. A1 - de Blois, E. A1 - Rohde, M. A1 - Paulßen, Elisabeth T1 - Measurement of reaction kinetics of [177Lu]Lu-DOTA-TATE using a microfluidic system JF - Dalton Transactions Y1 - 2017 U6 - http://dx.doi.org/10.1039/C7DT01830D SN - 1477-9234 VL - 46 IS - 42 SP - 14669 EP - 14676 ER - TY - JOUR A1 - Wilson, Ian D. A1 - Wilson, Claire E. A1 - Scheer, Nico A1 - Dickie, A.P. A1 - Schreiter, K. A1 - Wilson, E. M. A1 - Riley, R. J. A1 - Wehr, R. A1 - Bial, J. T1 - The Pharmacokinetics and Metabolism of Lumiracoxib in Chimeric Humanized and Murinized FRG Mice JF - Biochemical pharmacology Y1 - 2017 U6 - http://dx.doi.org/10.1016/j.bcp.2017.03.015 SN - 1873-2968 VL - Volume 135 SP - 139 EP - 150 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Samuelsson, K. A1 - Scheer, Nico A1 - Wilson, I. A1 - Wolf, C.R. A1 - Henderson, C.J. ED - Chackalamannil, Samuel T1 - Genetically Humanized Animal Models T2 - Comprehensive Medicinal Chemistry III. 3rd Edition N2 - Genetically humanized mice for proteins involved in drug metabolism and toxicity and mice engrafted with human hepatocytes are emerging as promising in vivo models for improved prediction of the pharmacokinetic, drug–drug interaction, and safety characteristics of compounds in humans. This is an overview on the genetically humanized and chimeric liver-humanized mouse models, which are illustrated with examples of their utility in drug metabolism and toxicity studies. The models are compared to give guidance for selection of the most appropriate model by highlighting advantages and disadvantages to be carefully considered when used for studies in drug discovery and development. KW - Chimeric liver-humanized mice KW - Drug distribution KW - Drug metabolism KW - Toxicology KW - Knockout mice Y1 - 2017 SN - 978-0-12-803201-5 U6 - http://dx.doi.org/10.1016/B978-0-12-409547-2.12376-5 SP - 130 EP - 149 PB - Elsevier CY - Saint Louis ER - TY - JOUR A1 - Mayer, Jan A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils A1 - Karimi-Varnaneh, Hossein Ali T1 - A Nano-Mechanical Instability as Primary Contribution to Rolling Resistance JF - Scientific Reports Y1 - 2017 SN - 2045-2322 VL - 7 IS - Article number 11275 PB - Springer CY - Berlin ER - TY - JOUR A1 - Meyer, Jan A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils A1 - Karimi-Varzaneh, Hossein Ali T1 - Molecular Simulation of Viscous Dissipation due to Cyclic Deformation of a Silica–Silica Contact in Filled Rubber JF - Macromolecules Y1 - 2017 U6 - http://dx.doi.org/10.1021/acs.macromol.7b00947 SN - 1520-5835 VL - 50 IS - 17 SP - 6679 EP - 6689 ER - TY - JOUR A1 - Druckenmüller, Katharina A1 - Günther, Klaus A1 - Elbers, Gereon T1 - Near-infrared spectroscopy (NIRS) as a tool to monitor exhaust air from poultry operations JF - Science of the Total Environment N2 - Intensive poultry operation systems emit a considerable volume of inorganic and organic matter in the surrounding environment. Monitoring cleaning properties of exhaust air cleaning systems and to detect small but significant changes in emission characteristics during a fattening cycle is important for both emission and fattening process control. In the present study, we evaluated the potential of near-infrared spectroscopy (NIRS) combined with chemometric techniques as a monitoring tool of exhaust air from poultry operation systems. To generate a high-quality data set for evaluation, the exhaust air of two poultry houses was sampled by applying state-of-the-art filter sampling protocols. The two stables were identical except for one crucial difference, the presence or absence of an exhaust air cleaning system. In total, twenty-one exhaust air samples were collected at the two sites to monitor spectral differences caused by the cleaning device, and to follow changes in exhaust air characteristics during a fattening period. The total dust load was analyzed by gravimetric determination and included as a response variable in multivariate data analysis. The filter samples were directly measured with NIR spectroscopy. Principal component analysis (PCA), linear discriminant analysis (LDA), and factor analysis (FA) were effective in classifying the NIR exhaust air spectra according to fattening day and origin. The results indicate that the dust load and the composition of exhaust air (inorganic or organic matter) substantially influence the NIR spectral patterns. In conclusion, NIR spectroscopy as a tool is a promising and very rapid way to detect differences between exhaust air samples based on still not clearly defined circumstances triggered during a fattening period and the availability of an exhaust air cleaning system. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.scitotenv.2018.02.072 SN - 0048-9697 VL - 630 SP - 536 EP - 543 PB - Elsevier CY - Amsterdam ER - TY - BOOK A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül A1 - Zhubanova, Azhar A. A1 - Digel, Ilya ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Biological, physical and technical basics of cell engineering Y1 - 2018 SN - 978-981-10-7903-0 PB - Springer CY - Singapore ER - TY - JOUR A1 - Molinnus, Denise A1 - Muschallik, Lukas A1 - Gonzalez, Laura Osorio A1 - Bongaerts, Johannes A1 - Wagner, Torsten A1 - Selmer, Thorsten A1 - Siegert, Petra A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Development and characterization of a field-effect biosensor for the detection of acetoin JF - Biosensors and Bioelectronics N2 - A capacitive electrolyte-insulator-semiconductor (EIS) field-effect biosensor for acetoin detection has been presented for the first time. The EIS sensor consists of a layer structure of Al/p-Si/SiO₂/Ta₂O₅/enzyme acetoin reductase. The enzyme, also referred to as butane-2,3-diol dehydrogenase from B. clausii DSM 8716T, has been recently characterized. The enzyme catalyzes the (R)-specific reduction of racemic acetoin to (R,R)- and meso-butane-2,3-diol, respectively. Two different enzyme immobilization strategies (cross-linking by using glutaraldehyde and adsorption) have been studied. Typical biosensor parameters such as optimal pH working range, sensitivity, hysteresis, linear concentration range and long-term stability have been examined by means of constant-capacitance (ConCap) mode measurements. Furthermore, preliminary experiments have been successfully carried out for the detection of acetoin in diluted white wine samples. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.bios.2018.05.023 VL - 115 SP - 1 EP - 6 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Yazici, Y. A1 - Selmer, Thorsten A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Application of a portable multi-analyte biosensor for organic acid determination in silage JF - Sensors N2 - Multi-analyte biosensors may offer the opportunity to perform cost-effective and rapid analysis with reduced sample volume, as compared to electrochemical biosensing of each analyte individually. This work describes the development of an enzyme-based biosensor system for multi-parametric determination of four different organic acids. The biosensor array comprises five working electrodes for simultaneous sensing of ethanol, formate, d-lactate, and l-lactate, and an integrated counter electrode. Storage stability of the biosensor was evaluated under different conditions (stored at +4 °C in buffer solution and dry at −21 °C, +4 °C, and room temperature) over a period of 140 days. After repeated and regular application, the individual sensing electrodes exhibited the best stability when stored at −21 °C. Furthermore, measurements in silage samples (maize and sugarcane silage) were conducted with the portable biosensor system. Comparison with a conventional photometric technique demonstrated successful employment for rapid monitoring of complex media. Y1 - 2018 U6 - http://dx.doi.org/10.3390/s18051470 SN - 1424-8220 VL - 18 IS - 5 PB - MDPI CY - Basel ER - TY - CHAP A1 - Artmann, Gerhard A1 - Meruvu, Haritha A1 - Kizildag, Sefa A1 - Temiz Artmann, Aysegül ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Functional Toxicology and Pharmacology Test of Cell Induced Mechanical Tensile Stress in 2D and 3D Tissue Cultures T2 - Biological, Physical and Technical Basics of Cell Engineering N2 - Mechanical forces/tensile stresses are critical determinants of cellular growth, differentiation and migration patterns in health and disease. The innovative “CellDrum technology” was designed for measuring mechanical tensile stress of cultured cell monolayers/thin tissue constructs routinely. These are cultivated on very thin silicone membranes in the so-called CellDrum. The cell layers adhere firmly to the membrane and thus transmit the cell forces generated. A CellDrum consists of a cylinder which is sealed from below with a 4 μm thick, biocompatible, functionalized silicone membrane. The weight of cell culture medium bulbs the membrane out downwards. Membrane indentation is measured. When cells contract due to drug action, membrane, cells and medium are lifted upwards. The induced indentation changes allow for lateral drug induced mechanical tension quantification of the micro-tissues. With hiPS-induced (human) Cardiomyocytes (CM) the CellDrum opens new perspectives of individualized cardiac drug testing. Here, monolayers of self-beating hiPS-CMs were grown in CellDrums. Rhythmic contractions of the hiPS-cells induce membrane up-and-down deflections. The recorded cycles allow for single beat amplitude, single beat duration, integration of the single beat amplitude over the beat time and frequency analysis. Dose effects of agonists and antagonists acting on Ca2+ channels were sensitively and highly reproducibly observed. Data were consistent with published reference data as far as they were available. The combination of the CellDrum technology with hiPS-Cardiomyocytes offers a fast, facile and precise system for pharmacological and toxicological studies. It allows new preclinical basic as well as applied research in pharmacolgy and toxicology. Y1 - 2018 SN - 978-981-10-7904-7 U6 - http://dx.doi.org/10.1007/978-981-10-7904-7_7 SP - 157 EP - 192 PB - Springer CY - Singapore ER - TY - CHAP A1 - Duong, Minh Tuan A1 - Seifarth, Volker A1 - Temiz Artmann, Aysegül A1 - Artmann, Gerhard A1 - Staat, Manfred ED - Artmann, Gerhard ED - Temiz Artmann, Aysegül ED - Zhubanova, Azhar A. ED - Digel, Ilya T1 - Growth Modelling Promoting Mechanical Stimulation of Smooth Muscle Cells of Porcine Tubular Organs in a Fibrin-PVDF Scaffold T2 - Biological, Physical and Technical Basics of Cell Engineering N2 - Reconstructive surgery and tissue replacements like ureters or bladders reconstruction have been recently studied, taking into account growth and remodelling of cells since living cells are capable of growing, adapting, remodelling or degrading and restoring in order to deform and respond to stimuli. Hence, shapes of ureters or bladders and their microstructure change during growth and these changes strongly depend on external stimuli such as training. We present the mechanical stimulation of smooth muscle cells in a tubular fibrin-PVDFA scaffold and the modelling of the growth of tissue by stimuli. To this end, mechanotransduction was performed with a kyphoplasty balloon catheter that was guided through the lumen of the tubular structure. The bursting pressure was examined to compare the stability of the incubated tissue constructs. The results showed the significant changes on tissues with training by increasing the burst pressure as a characteristic mechanical property and the smooth muscle cells were more oriented with uniformly higher density. Besides, the computational growth models also exhibited the accurate tendencies of growth of the cells under different external stimuli. Such models may lead to design standards for the better layered tissue structure in reconstructing of tubular organs characterized as composite materials such as intestines, ureters and arteries. KW - Mechanical simulation KW - Growth modelling KW - Ureter KW - Bladder KW - Reconstruction Y1 - 2018 SN - 978-981-10-7904-7 U6 - http://dx.doi.org/10.1007/978-981-10-7904-7_9 SP - 209 EP - 232 PB - Springer CY - Singapore ER - TY - JOUR A1 - Aboulnaga, E. A. A1 - Zou, H. A1 - Selmer, Thorsten A1 - Xian, M. T1 - Development of a plasmid-based, tunable, tolC-derived expression system for application in Cupriavidus necator H16 JF - Journal of Biotechnology N2 - Cupriavidus necator H16 gains increasing attention in microbial research and biotechnological application due to its diverse metabolic features. Here we present a tightly controlled gene expression system for C. necator including the pBBR1-vector that contains hybrid promoters originating from C. necator native tolC-promoter in combination with a synthetic tetO-operator. The expression of the reporter gene from these plasmids relies on the addition of the exogenous inducer doxycycline (dc). The novel expression system offers a combination of advantageous features as; (i) high and dose-dependent recombinant protein production, (ii) tight control with a high dynamic range (On/Off ratio), which makes it applicable for harmful pathways or for toxic protein production, (iii) comparable cheap inducer (doxycycline, dc), (iv) effective at low inducer concentration, that makes it useful for large scale application, (v) rapid, diffusion controlled induction, and (vi) the inducer does not interfere within the cell metabolism. As applications of the expression system in C. necator H16, the growth ability on glycerol was enhanced by constitutively expressing the E. coli glpk gene-encoding for glycerol kinase. Likewise, we used the system to overcome the expression toxicity of mevalonate pathway in C. necator H16. With this system, the mevalonate-genes were successfully introduced in the host and the recombinant strains could produce about 200 mg/l mevalonate. Y1 - 2018 U6 - http://dx.doi.org/10.1016/j.jbiotec.2018.03.007 SN - 0168-1656 VL - 274 SP - 15 EP - 27 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Teumer, T. A1 - Capitain, C. A1 - Ross-Jones, J. A1 - Tippkötter, Nils A1 - Rädle, M. A1 - Methner, F.-J. T1 - In-line Haze Monitoring Using a Spectrally Resolved Back Scattering Sensor JF - BrewingScience N2 - In the present work an optical sensor in combination with a spectrally resolved detection device for in-line particle-size-monitoring for quality control in beer production is presented. The principle relies on the size and wavelength dependent backscatter of growing particles in fluids. Measured interference structures of backscattered light are compared with calculated theoretical values, based on Mie-Theory, and fitted with a linear least square method to obtain particle size distributions. For this purpose, a broadband light source in combination with a process-CCD-spectrometer (charge ? coupled device spectrometer) and process adapted fiber optics are used. The goal is the development of an easy and flexible measurement device for in-line-monitoring of particle size. The presented device can be directly installed in product fill tubes or vessels, follows CIP- (cleaning in place) and removes the need of sample taking. A proof of concept and preliminary results, measuring protein precipitation, are presented. Y1 - 2018 SN - 1613-2041 VL - 71 IS - 5/6 SP - 49 EP - 55 PB - Fachverlag Hans Carl CY - Nürnberg ER - TY - CHAP A1 - Duwe, A. A1 - Tippkötter, Nils A1 - Ulber, R. T1 - Lignocellulose-Biorefinery: Ethanol-Focused T2 - Biorefineries N2 - The development prospects of the world markets for petroleum and other liquid fuels are diverse and partly contradictory. However, comprehensive changes for the energy supply of the future are essential. Notwithstanding the fact that there are still very large deposits of energy resources from a geological point of view, the finite nature of conventional oil reserves is indisputable. To reduce our dependence on oil, the EU, the USA, and other major economic zones rely on energy diversification. For this purpose, alternative materials and technologies are being sought, and is most obvious in the transport sector. The objective is to progressively replace fossil fuels with renewable and more sustainable fuels. In this respect, biofuels have a pre-eminent position in terms of their capability of blending with fossil fuels and being usable in existing cars without substantial modification. Ethanol can be considered as the primary renewable liquid fuel. In this chapter enzymes, micro-organisms, and processes for ethanol production based on renewable resources are described. KW - Bioethanol KW - Biorefinery KW - Lignocellulose feedstook Y1 - 2018 U6 - http://dx.doi.org/10.1007/10_2016_72 N1 - Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE,volume 166) SP - 177 EP - 215 PB - Springer CY - Cham ER -