@article{ScheerWilson2016, author = {Scheer, Nico and Wilson, Ian D.}, title = {A comparison between genetically humanized and chimeric liver humanized mouse models for studies in drug metabolism and toxicity}, series = {Drug Discovery Today}, volume = {21}, journal = {Drug Discovery Today}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2015.09.002}, pages = {250 -- 263}, year = {2016}, abstract = {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.}, language = {en} } @incollection{ScheerChuSalphatietal.2016, author = {Scheer, Nico and Chu, Xiaoyan and Salphati, Laurent and Zamek-Gliszczynski, Maciej J.}, title = {Knockout and humanized animal models to study membrane transporters in drug development}, series = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development}, booktitle = {Drug Transporters: Volume 1: Role and Importance in ADME and Drug Development}, editor = {Nicholls, Glynis}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, isbn = {978-1-78262-379-3}, doi = {10.1039/9781782623793-00298}, pages = {298 -- 332}, year = {2016}, language = {en} } @article{PaulssenLengkeekLeetal.2016, author = {Paulßen, Elisabeth and Lengkeek, Nigel A. and Le, Van So and Pellegrini, Paul A. and Greguric, Ivan and Weiner, Ron}, title = {The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [⁶⁸Ga(DOTATATE)]}, series = {Applied Radiation and Isotopes}, volume = {107}, journal = {Applied Radiation and Isotopes}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9800}, doi = {10.1016/j.apradiso.2015.09.008}, pages = {13 -- 16}, year = {2016}, abstract = {[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.}, language = {en} } @article{InfantinoPaulssenMostaccietal.2016, author = {Infantino, Angelo and Paulßen, Elisabeth and Mostacci, Domiziano and Schaffer, Paul and Trinczek, Michael and Hoehr, Cornelia}, title = {Assessment of the production of medical isotopes using the Monte Carlo code FLUKA: Simulations against experimental measurements}, series = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms}, volume = {366}, journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9584}, doi = {10.1016/j.nimb.2015.10.067}, pages = {117 -- 123}, year = {2016}, abstract = {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.}, language = {en} } @article{NiedermeyerZhouDursunetal.2016, author = {Niedermeyer, Angela and Zhou, Bei and Dursun, G{\"o}zde and Temiz Artmann, Ayseg{\"u}l and Markert, Bernd}, title = {An examination of tissue engineered scaffolds in a bioreactor}, series = {Proceedings in Applied Mathematics and Mechanics PAMM}, volume = {16}, journal = {Proceedings in Applied Mathematics and Mechanics PAMM}, number = {1}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1617-7061}, doi = {10.1002/pamm.201610038}, pages = {99 -- 100}, year = {2016}, abstract = {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.}, language = {en} } @article{SvaneborgKarimiVarzanehHojdisetal.2016, author = {Svaneborg, Carsten and Karimi-Varzaneh, Hossein Ali and Hojdis, Nils and Fleck, Franz and Everaers, Ralf}, title = {Multiscale approach to equilibrating model polymer melts}, series = {Physical Review E}, volume = {94}, journal = {Physical Review E}, number = {032502}, publisher = {AIP Publishing}, address = {Melville, NY}, issn = {2470-0053}, doi = {10.1103/PhysRevE.94.032502}, year = {2016}, abstract = {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.}, language = {en} } @article{SchwabHojdisLacayoetal.2016, author = {Schwab, Lukas and Hojdis, Nils and Lacayo, Jorge and Wilhelm, Manfred}, title = {Fourier-Transform Rheology of Unvulcanized, Carbon Black Filled Styrene Butadiene Rubber}, series = {Macromolecular Materials and Engineering}, volume = {301}, journal = {Macromolecular Materials and Engineering}, number = {4}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1439-2054}, doi = {10.1002/mame.201500356}, pages = {457 -- 468}, year = {2016}, abstract = {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.}, language = {en} } @article{HarishWriggersJungketal.2016, author = {Harish, Ajay B. and Wriggers, Peter and Jungk, Juliane and Hojdis, Nils and Recker, Carla}, title = {Mesoscale Constitutive Modeling of Non-Crystallizing Filled Elastomers}, series = {Computational Mechanics}, volume = {57}, journal = {Computational Mechanics}, publisher = {Springer}, address = {Berlin}, issn = {1432-0924}, doi = {10.1007/s00466-015-1251-1}, pages = {653 -- 677}, year = {2016}, abstract = {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.}, language = {en} } @inproceedings{HeringUlberTippkoetter2016, author = {Hering, T. and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Development of a screening system for antimicrobial surfaces}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {129}, year = {2016}, language = {en} } @inproceedings{CapitainHeringTippkoetteretal.2016, author = {Capitain, C. and Hering, T. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Enzymatic polymerization of lignin model compounds and solubilized lignin in an aqueous ethanol extract}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {151 -- 152}, year = {2016}, language = {en} } @inproceedings{EngelThieringerTippkoetter2016, author = {Engel, M. and Thieringer, J. and Tippk{\"o}tter, Nils}, title = {Microbial electrosynthesis for sustainable biobutanol production}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {77 -- 78}, year = {2016}, language = {en} } @article{MolinnusSorichBartzetal.2016, author = {Molinnus, Denise and Sorich, Maren and Bartz, Alexander and Siegert, Petra and Willenberg, Holger S. and Lisdat, Fred and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate}, series = {Sensors and Actuators B: Chemical}, volume = {237}, journal = {Sensors and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.06.064}, pages = {190 -- 195}, year = {2016}, abstract = {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.}, language = {en} } @misc{MoehringWulfhorstCapitainetal.2016, author = {M{\"o}hring, S. and Wulfhorst, H. and Capitain, C. and Roth, J. and Tippk{\"o}tter, Nils}, title = {Fractioning of lignocellulosic biomass: Scale-down and automation of thermal pretreatment for parameter optimization}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650288}, pages = {1229}, year = {2016}, abstract = {In order to efficiently convert lignocellulose, it is often necessary to conduct a pretreatment. The biomass considered in this study typically comprises of agricultural and horticultural residues, as well as beechwood. A very environmentally friendly method, namely, fungal pretreatment using white-rot fungi, leads to an enhanced enzymatic hydrolysis. In contrast to other processes presented, the energy input is extremely low. However, the fungal growth on the lignocellulosic substrates takes several weeks at least in order to be effective. Thus, the reduction of chemicals and energy for thermal processing is a target of our current research. Liquid hot water (LHW) and solvent-based pretreatment (OrganoSolv) require more complex equipment, as they depend on high temperatures (160 - 180 °C) and enhanced pressure (up to 20 bar). However, they prove to be promising processes in regard to the fractioning of lignocellulose. For optimal lignin recovery the parameters differ from those established in cellulose extraction. A novel screening system scaled down to a reaction volume of 100 mL has been developed and successfully tested for this purpose.}, language = {en} } @inproceedings{EngelThieringerTippkoetter2016, author = {Engel, Mareike and Thieringer, Julia and Tippk{\"o}tter, Nils}, title = {Linking bioprocess engineering and electrochemistry for sustainable biofuel production}, series = {Young Researchers Symposium, YRS 2016. Proceedings}, booktitle = {Young Researchers Symposium, YRS 2016. Proceedings}, publisher = {Fraunhofer Verlag}, address = {Karlsruhe}, pages = {49 -- 53}, year = {2016}, abstract = {Electromicrobial engineering is an emerging, highly interdisciplinary research area linking bioprocesses with electrochemistry. In this work, microbial electrosynthesis (MES) of biobutanol is carried out during acetone-butanol-ethanol (ABE) fermentations with Clostridium acetobutylicum. A constant electric potential of -600mV (vs. Ag/AgCl) with simultaneous addition of the soluble redox mediator neutral red is used in order to study the electron transfer between the working electrode and the bacterial cells. The results show an earlier initiation of solvent production for all fermentations with applied potential compared to the conventional ABE fermentation. The f inal butanol concentration can be more than doubled by the application of a negative potential combined with addition of neutral red. Moreover a higher biofilm formation on the working electrode compared to control cultivations has been observed. In contrast to previous studies, our results also indicate that direct electron transfer (DET) might be possible with C. acetobutylicum. The presented results make microbial butanol production economically attractive and therefore support the development of sustainable production processes in the chemical industry aspired by the "Centre for resource-efficient chemistry and raw material change" as well as the the project "NanoKat" working on nanostructured catalysts in Kaiserslautern.}, language = {en} } @article{ZhangHeimbachScheeretal.2016, author = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan}, title = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling}, series = {Journal of Pharmaceutical Sciences}, volume = {Volume 105}, journal = {Journal of Pharmaceutical Sciences}, number = {Issue 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-3549}, doi = {doi.org/10.1016/j.xphs.2016.01.021}, pages = {1398 -- 1404}, year = {2016}, abstract = {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.}, language = {en} } @article{DallasSalphatiGomezZepedaetal.2016, author = {Dallas, Shannon and Salphati, Laurent and Gomez-Zepeda, David and Wanek, Thomas and Chen, Liangfu and Chu, Xiaoyan and Kunta, Jeevan and Mezler, Mario and Menet, Marie-Claude and Chasseigneaux, Stephanie and Decl{\`e}ves, Xavier and Langer, Oliver and Pierre, Esaie and DiLoreto, Karen and Hoft, Carolin and Laplanche, Loic and Pang, Jodie and Pereira, Tony and Andonian, Clara and Simic, Damir and Rode, Anja and Yabut, Jocelyn and Zhang, Xiaolin and Scheer, Nico}, title = {Generation and Characterization of a Breast Cancer Resistance Protein Humanized Mouse Model}, series = {Molecular Pharmacology}, volume = {89}, journal = {Molecular Pharmacology}, number = {5}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.115.102079}, pages = {492 -- 504}, year = {2016}, abstract = {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.}, language = {en} } @misc{HeringUlberTippkoetter2016, author = {Hering, T. and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Antimikrobielle Oberfl{\"a}chenmodifikation durch Mikropartikel}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/cite.201650084}, pages = {1302}, year = {2016}, abstract = {Die Ausbildung von Biofilmen in technischen Anlagen, wie z. B. K{\"u}hlkreisl{\"a}ufen, Wasseraufbereitungssystemen und Bioreaktoren, f{\"u}hren zu Materialsch{\"a}den (Biofouling) und stark erh{\"o}htem Energieaufwand. Im Rahmen der aktuellen Forschungsarbeiten erfolgen aktive sowie passive Bio-Modifikationen auf funktionalisierten magnetischen Mikropartikelober-fl{\"a}chen. Um die verschiedenen funktionalisierten magnetischen Mikropartikel zu analysieren und ihre antimikrobielle Wirkung zu testen, wird der Einsatz einer 3D-gedruckten, magnetischen Plattform f{\"u}r ein Fluoreszenz-basiertes Screening-System untersucht. F{\"u}r den Oberfl{\"a}chenschutz wurden verschiedene, antimikrobiell funktionalisierte Partikelkombinationen mit dem Mikroorganismus Escherichia coli GFPmut2 in Bezug auf aktiven Oberfl{\"a}chenschutz verglichen. Um die antimikrobielle Oberfl{\"a}cheneffekte von synergistischen Kombinationen unterschiedlich funktionalisierter Partikel zu bestimmen, werden Oberfl{\"a}chen einem Magnetfeld ausgesetzt, das die Mikropartikel als definierte Schicht auf ihnen zur{\"u}ck h{\"a}lt. Diese modifizierten Oberfl{\"a}chen k{\"o}nnen sowohl durch Fluoreszenzspektroskopie als auch -mikroskopie analysiert werden.}, language = {de} } @article{RoeschKratzHeringetal.2016, author = {R{\"o}sch, C. and Kratz, F. and Hering, T. and Trautmann, S. and Umanskaya, N. and Tippk{\"o}tter, Nils and M{\"u}ller-Renno, C.M. and Ulber, Roland and Hannig, M. and Ziegler, C.}, title = {Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity}, series = {Colloids and Surfaces B: Biointerfaces}, volume = {149}, journal = {Colloids and Surfaces B: Biointerfaces}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.colsurfb.2016.09.048}, pages = {115 -- 121}, year = {2016}, abstract = {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.}, language = {en} } @article{WulfhorstDuweMerseburgetal.2016, author = {Wulfhorst, Helene and Duwe, Anna-Maria and Merseburg, Johannes and Tippk{\"o}tter, Nils}, title = {Compositional analysis of pretreated (beech) wood using differential scanning calorimetry and multivariate data analysis}, series = {Tetrahedron}, volume = {72}, journal = {Tetrahedron}, number = {46}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.tet.2016.04.029}, pages = {7329 -- 7334}, year = {2016}, abstract = {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.}, language = {en} } @misc{AlKaidyTippkoetterUlber2016, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Vorrichtung und Verfahren zur Bestimmung des Kontaktwinkels eines Fl{\"u}ssigk{\"o}rpers mit einer Festk{\"o}rperoberfl{\"a}che}, year = {2016}, abstract = {Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Bestimmung des Kontaktwinkels eines fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rpers. Dieser besteht aus einem Tr{\"a}ger (1) und einer damit verbundenen, in einem Winkelbereich von mehr als 0 ° bis maximal 90 ° neigbaren Ebene (8) mit einer darin ausgebildeten Abrollbahn (9) f{\"u}r den fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rper. An der Ebene (8) sind mehrere Sensoren (11,12) zur Erfassung der Rolldauer des K{\"o}rpers entlang der Rollstrecke angeordnet. Erfindungsgem{\"a}ß ist vorgesehen, dass die Einstellung des Neigungswinkels der Ebene (8) {\"u}ber ein Winkelmessger{\"a}t (10) erfolgt, wodurch ein Abrollwinkel erfassbar ist, bei dem der K{\"o}rper in Bewegung ger{\"a}t. Aus der Rolldauer, der Rollstrecke und dem Abrollwinkel wird der Kontaktwinkel des K{\"o}rpers ermittelt.}, language = {de} } @article{RothTippkoetter2016, author = {Roth, Jasmine and Tippk{\"o}tter, Nils}, title = {Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium}, series = {Cellulose Chemistry and Technology}, volume = {50}, journal = {Cellulose Chemistry and Technology}, number = {3-4}, publisher = {Editura Academiei Romane}, address = {Bukarest}, pages = {405 -- 410}, year = {2016}, abstract = {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.}, language = {en} } @misc{EngelTippkoetter2016, author = {Engel, M. and Tippk{\"o}tter, Nils}, title = {Einfluss eines Phenazin-Mediators und elektrischen Potenzials auf die Aceton-Butanol-Ethanol-Fermentation}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650105}, pages = {1254}, year = {2016}, abstract = {In den letzten Jahren haben nachhaltige, biotechnologische Prozesse zunehmend an Bedeutung gewonnen. Die Aceton-Butanol-Ethanol-Fermentation (ABE-Fermentation) mit dem anaeroben Bakterium Clostridium acetobutylicum zur Gewinnung von Biobutanol k{\"o}nnte in diesem Zusammenhang eine M{\"o}glichkeit der nachhaltigen Kraftstoffproduktion darstellen. In dieser Arbeit wird der Einfluss zus{\"a}tzlich verf{\"u}gbarer Elektronen durch den Einsatz des Phenazin-Farbstoffs Neutralrot als Redoxmediator sowie das Anlegen eines elektrischen Potenzials w{\"a}hrend der ABE-Fermentation untersucht. Es wird gezeigt, dass das Neutralrot keinen Einfluss auf die Leerlaufspannung von ca. 500 mV vs. Ag/AgCl w{\"a}hrend der Fermentation hat. Der Mediator bewirkt allerdings eine fr{\"u}here Butanolbildung sowie h{\"o}here Butanolkonzentrationen. Wird zudem die Mediatorkonzentration von 125 mM auf 250 mM angehoben, wird dabei auch die maximale Butanolkonzentration um 36 \% ± 1,8 \% innerhalb von28 Stunden gesteigert.}, language = {de} } @misc{WulfhorstMerseburgTippkoetter2016, author = {Wulfhorst, H. and Merseburg, J. and Tippk{\"o}tter, Nils}, title = {Batteriekomponenten aus nachwachsenden Rohstoffen}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650333}, pages = {1234 -- 1235}, year = {2016}, abstract = {In diesem Beitrag geht es um die Integration von Stoffstr{\"o}men einer Lignocellulose-Bioraffinerie in Verfahren zur Batterieherstellung. Pflanzliche Reststoffe aus der Biokraftstoffherstellung wie Lignin sollen zur Herstellung neuer Batteriematerialien verwendet werden. Hierbei wird das Lignin als Matrix f{\"u}r die vorgraphitischen C-haltigen Einlagerungsverbindungen in den Elektroden genutzt. Die Si-C-Komposite werden durch das Einbetten von Si in eine Ligninmatrix mit anschließender Carbonisierung hergestellt. Das Lignin hierf{\"u}r wird durch die sequentielle hydrothermale Vorbehandlung von Buchenholz bei variablen Bedingungen gewonnen und mit Si-Nanopartikel sowie als Referenz ohne Si-Nanopartikel gef{\"a}llt. Die Ergebnisse zeigen, dass die sequenzielle Vorbehandlung h{\"o}here Ausbeuten im Vergleich zum LHW- oder Organosolv-Aufschluss liefert. Um eine Anode herzustellen, wurde das resultierende Si-C-Kompositmaterial carbonisiert, auf einen Stromsammler aufgetragen und elektro-chemisch charakterisiert. Der Einfluss der Vorbehandlungsschritte auf den Herstellungsprozess und die {\"o}konomische Bewertung des untersuchten Bioraffinerie-Prozesses wurde mithilfe eines Stoffstrommodells analysiert.}, language = {de} } @misc{RothTippkoetter2016, author = {Roth, J. and Tippk{\"o}tter, Nils}, title = {New Approach for Enzymatic Hydrolysis of Lignocellulose with Selective Diffusion Separation of the Monosaccharide Products}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650301}, pages = {1237}, year = {2016}, abstract = {Enzymatic hydrolysis of lignocellulosic material plays an important role in the classical biorefinery approach. Apart from the pretreatment of the raw material, hydrolysis is the basis for the conversion of the cellulose and hemicellulose fraction into fermentable sugars. After hydrolysis, usually a solid-liquid separation takes place, in order to separate the residual plant material from the sugar-rich fraction, which can be subsequently used in a fermentation step. In order to factor out the separation step, the usage of in alginate immobilized crude cellulose fiber beads (CFBs) were evaluated. Pretreated cellulose fibers are incorporated in an alginate matrix together with the relevant enzymes. In doing so, sugars diffuse trough the alginate matrix, allowing a simplified delivery into the surrounding fluid. This again reduces product inhibition of the glucose on the enzyme catalysts. By means of standardized bead production the hydrolysis in lab scale was possible. First results show that liberation of glucose and xylose is possible, allowing a maximum total sugar yield of 75 \%.}, language = {en} } @misc{CapitainHeringTippkoetter2016, author = {Capitain, C. and Hering, T. and Tippk{\"o}tter, Nils}, title = {Enzymatische Polymerisation von Ligninmodellkomponenten und Organosolv-Lignin mit aromatischen Aminos{\"a}uren}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201650374}, pages = {1236}, year = {2016}, abstract = {Die stoffliche Nutzung von Lignin aus Bioraffinerien ist ein wichtiger Bestandteil f{\"u}r den Wertsch{\"o}pfungsprozess von nachwachsenden, pflanzlichen Rohstoffen. Lignin z{\"a}hlt zu den wenigen erneuerbaren Quellen f{\"u}r phenolische Bestandteile, wird aber derzeit meist nur thermisch verwertet. Ziel dieses Forschungsvorhabens ist die Funktionalisierung von Lignin zur Verbesserung der Adh{\"a}sionseigenschaften. Als funktionelle Gruppe wird die aromatische Aminos{\"a}ure L-DOPA verwendet, die charakteristisch f{\"u}r die Adh{\"a}sionskraft von Muscheln ist. Lignin ist ein geeignetes St{\"u}tzger{\"u}st, da es ein Polymer ist, das durch enzymkatalysierte Polymerisation gebildet wird. Essenziell f{\"u}r die Entwicklung ist ein besseres Verst{\"a}ndnis {\"u}ber die Bildung von Lignin-Polymeren und deren verschiedene Eigenschaften. Um die Einflussfaktoren auf Kettenl{\"a}nge und Polymerisationseffizienz zu untersuchen, werden zurzeit sowohl Ligninmodellkomponenten (LMK) als auch gel{\"o}stes Organosolv-Lignin verwendet. Laufende Untersuchungen werden zeigen, ob sich die enzymatische Polymerisationsreaktion auf ein gel{\"o}stes Ligninpolymer aus einem Organosolv-Aufschluss {\"u}bertragen l{\"a}sst.}, language = {de} } @incollection{Tippkoetter2016, author = {Tippk{\"o}tter, Nils}, title = {Grundlagen der bio-chemischen Umwandlung}, series = {Energie aus Biomasse : Grundlagen, Techniken und Verfahren}, booktitle = {Energie aus Biomasse : Grundlagen, Techniken und Verfahren}, editor = {Kaltschmidt, Martin}, edition = {3., aktualisierte, erweiterte Auflage}, publisher = {Springer Vieweg}, address = {Berlin ; Heidelberg}, isbn = {978-3-662-47437-2 (Print)}, doi = {10.1007/978-3-662-47438-9}, pages = {1447 -- 1500}, year = {2016}, language = {de} } @misc{KuthanAlKaidyTippkoetter2016, author = {Kuthan, K. and Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils}, title = {Tropfenbasierte Enzymreaktionen auf Glasoberfl{\"a}chen im μL-Maßstab mit ortsaufgel{\"o}ster pL-Dosierung der Reaktanden}, series = {Chemie Ingenieur Technik}, volume = {88}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/cite.201650117}, pages = {1336 -- 1337}, year = {2016}, abstract = {Mit der Entwicklung w{\"a}ssriger Tropfen, die mit einer sch{\"u}tzenden H{\"u}lle magnetisierbarer, hydrophober Partikel umgeben sind, ergeben sich neue M{\"o}glichkeiten im Bereich der Mikrofluidik. So k{\"o}nnen die Tropfen als fl{\"u}ssige Mikroreaktoren eingesetzt werden. Der w{\"a}ssrige Kern dieser Mikroreaktoren besteht aus einer Substratl{\"o}sung f{\"u}r enzymatische Umsetzungen. Durch Bewegen der Mikroreaktoren k{\"o}nnen diese {\"u}ber immobilisierten Enzymen positioniert werden, um so einen enzymatischen Umsatz innerhalb der Mikroreaktoren zu realisieren. Hierf{\"u}r wurde eine neue Mikroreaktorplattform-Technologie etabliert. Die Mikroreaktoren k{\"o}nnen aufgrund ihrer magnetisierbaren H{\"u}llenpartikel {\"u}ber elektromagnetische Spulen bewegt werden. Die Bewegung erfolgt dabei mit einer automatisierten Aktuatorplattform, bestehend aus einer 3x3 Doppelspulenmatrix mit Magnetkernen. Als modellhaftes Reaktionssystem wird eine Enzymkaskade eingesetzt, die sich aus einer b-Glucosidase, Glucose-Oxidase und Meerrettichperoxidase zusammensetzt. Prim{\"a}r untersuchte Substrate sind Fluorescein-di-b-D-glucopyranoside, und 1-(3,7-Dihydroxy-10H-phenoxazin-10-yl)-ethanon, bei deren Umsatz fluoreszierende Produkte entstehen.}, language = {de} } @article{PilasIkenSelmeretal.2015, author = {Pilas, Johanna and Iken, Heiko and Selmer, Thorsten and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Development of a multi-parameter sensor chip for the simultaneous detection of organic compounds in biogas processes}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431894}, pages = {1306 -- 1312}, year = {2015}, abstract = {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.}, language = {en} } @article{BreuerRaueKirschbaumetal.2015, author = {Breuer, Lars and Raue, Markus and Kirschbaum, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431944}, pages = {1368 -- 1374}, year = {2015}, abstract = {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.}, language = {en} } @article{KuschRieserKnuppetal.2015, author = {Kusch, Peter and Rieser, Claudia and Knupp, Gerd and Mang, Thomas}, title = {Characterization of copolymers of methacrylic acid with poly(ethylene glycol) methyl ether methacrylate macromonomers by analytical pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS)}, series = {Journal of Analytical and Applied Pyrolysis}, volume = {Vol. 113}, journal = {Journal of Analytical and Applied Pyrolysis}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0165-2370}, doi = {10.1016/j.jaap.2015.03.003}, pages = {412 -- 418}, year = {2015}, language = {de} } @article{SchiffelsSelmer2015, author = {Schiffels, Johannes and Selmer, Thorsten}, title = {A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro}, series = {Biotechnology and Bioengineering}, volume = {112}, journal = {Biotechnology and Bioengineering}, number = {11}, publisher = {Wiley}, address = {Weinheim}, issn = {1097-0290}, doi = {10.1002/bit.25658}, pages = {2360 -- 2372}, year = {2015}, language = {en} } @article{PilasMarianoKeusgenetal.2015, author = {Pilas, Johanna and Mariano, K. and Keusgen, M. and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.702}, pages = {532 -- 535}, year = {2015}, language = {en} } @article{CehreliAkpinarTemizArtmannetal.2015, author = {Cehreli, Ruksan and Akpinar, Hale and Temiz Artmann, Ayseg{\"u}l and Sagol, Ozgul}, title = {Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis}, series = {Gastroenterology Research}, volume = {8}, journal = {Gastroenterology Research}, number = {5}, issn = {1918-2813}, doi = {10.14740/gr683w}, pages = {265 -- 273}, year = {2015}, language = {en} } @inproceedings{SrivastavaKnolleSchnugetal.2015, author = {Srivastava, Alok and Knolle, F. and Schnug, E. and Scherer, Ulrich W.}, title = {Study of Trace Elements in Water Bodies of the Harz Mts. Region, Germany using Total Reflection X Ray Fluorescence (TXRF)}, series = {DAE-BRNS 12th National Symposium on Nuclear and Radiochemistry NUCAR 2015, Feb. 9-13, Mumbai, India, Mumbai, India; 02/2015}, booktitle = {DAE-BRNS 12th National Symposium on Nuclear and Radiochemistry NUCAR 2015, Feb. 9-13, Mumbai, India, Mumbai, India; 02/2015}, pages = {355 -- 356}, year = {2015}, language = {de} } @incollection{SrivastavaKnolleHoyleretal.2015, author = {Srivastava, Alok and Knolle, Friedhart and Hoyler, Friedrich and Scherer, Ulrich W. and Schnug, Ewald}, title = {Uranium Toxicity in the State of Punjab in North-Western India}, series = {Management of Natural Resources in a Changing Environment}, booktitle = {Management of Natural Resources in a Changing Environment}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-12559-6}, doi = {10.1007/978-3-319-12559-6_21}, pages = {271 -- 275}, year = {2015}, abstract = {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.}, language = {en} } @book{MuellerRath2015, author = {M{\"u}ller, Bodo and Rath, Walter}, title = {Formulierung von Kleb- und Dichtstoffen: das kompetente Lehrbuch f{\"u}r Studium und Praxis}, edition = {3., vollst. {\"u}berarb. Aufl.}, publisher = {Vincentz Network}, address = {Hannover}, isbn = {978-3-86630-605-9}, pages = {375 S. : Ill., graph. Darst}, year = {2015}, language = {de} } @article{TakenagaSchneiderErbayetal.2015, author = {Takenaga, Shoko and Schneider, Benno and Erbay, E. and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and Wagner, Torsten}, title = {Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201532053}, pages = {1347 -- 1352}, year = {2015}, abstract = {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.}, language = {en} } @inproceedings{BreuerRaueMangetal.2015, author = {Breuer, Lars and Raue, Markus and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, Ronald and Wagner, Torsten}, title = {Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications}, series = {12. Dresdner Sensor-Symposium 2015}, booktitle = {12. Dresdner Sensor-Symposium 2015}, doi = {10.5162/12dss2015/P5.8}, pages = {206 -- 209}, year = {2015}, language = {en} } @misc{HuschyarTippkoetterUlber2015, author = {Huschyar, Al-Kaidy and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {System und Verfahren zur Durchf{\"u}hrung von chemischen, biologischen oder physikalischen Reaktionen}, year = {2015}, language = {de} } @article{ThielMufflerTippkoetteretal.2015, author = {Thiel, Alexander and Muffler, Kai and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Hruschka, Steffen M. and Ulber, Roland}, title = {A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal}, series = {Journal of Chemical Technology and Biotechnology}, volume = {90}, journal = {Journal of Chemical Technology and Biotechnology}, number = {11}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/jctb.4664}, pages = {1999 -- 2006}, year = {2015}, abstract = {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}, language = {en} } @article{VoigtAlbrechtSieversetal.2015, author = {Voigt, Birgit and Albrecht, Dirk and Sievers, Susanne and Becher, D{\"o}rte and Bongaerts, Johannes and Evers, Stefan and Schweder, Thomas and Maurer, Karl-Heinz and Hecker, Michael}, title = {High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium}, series = {Proteomics}, volume = {15}, journal = {Proteomics}, number = {15}, publisher = {Wiley}, address = {Weinheim}, issn = {1615-9861}, doi = {10.1002/pmic.201400504}, pages = {2629 -- 2633}, year = {2015}, language = {en} } @misc{StadtmuellerTippkoetterUlber2015, author = {Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Method for production of single-stranded macronucleotides}, year = {2015}, abstract = {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.}, language = {en} } @incollection{WolfKapelyukhScheeretal.2015, author = {Wolf, C. Roland and Kapelyukh, Yury and Scheer, Nico and Henderson, Colin J.}, title = {Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs}, editor = {Wilson, Alan G. E.}, publisher = {RSC Publ.}, address = {Cambridge}, isbn = {978-1-78262-778-4}, doi = {10.1039/9781782622376-00152}, pages = {152 -- 176}, year = {2015}, abstract = {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.}, language = {en} } @article{PaulssenHoehrHouetal.2015, author = {Paulßen, Elisabeth and Hoehr, Cornelia and Hou, Xinchi and Hanemaayer, Victoire and Zeisler, Stefan and Adam, Michael J. and Ruth, Thomas J. and Celler, Anna and Buckley, Ken and Benard, Francois and Schaffer, Paul}, title = {Production of Y-86 and other radiometals for research purposes using a solution target system}, series = {Nuclear medicine and biology}, volume = {42}, journal = {Nuclear medicine and biology}, number = {11}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9614}, doi = {10.1016/j.nucmedbio.2015.06.005}, pages = {842 -- 849}, year = {2015}, language = {en} } @article{HagerHentschkeHojdisetal.2015, author = {Hager, Jonathan and Hentschke, Reinhard and Hojdis, Nils and Karimi-Varzaneh, Hossein Ali}, title = {Computer Simulation of Particle-Particle Interaction in a Model Polymer Nanocomposite}, series = {Macromolecules}, volume = {48}, journal = {Macromolecules}, number = {24}, issn = {1520-5835}, doi = {10.1021/acs.macromol.5b01864}, pages = {9039 -- 9049}, year = {2015}, language = {en} } @book{LauthKowalczyk2015, author = {Lauth, Jakob and Kowalczyk, J{\"u}rgen}, title = {Thermodynamik : eine Einf{\"u}hrung}, publisher = {Springer Spektrum}, address = {Berlin}, isbn = {978-3-662-46228-7}, doi = {10.1007/978-3-662-46229-4}, pages = {XVIII, 380 S.: Ill., graph. Darst.}, year = {2015}, language = {de} } @article{SeifarthGossmannGrosseetal.2015, author = {Seifarth, Volker and Goßmann, Matthias and Grosse, J. O. and Becker, C. and Heschel, I. and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds}, series = {Urologia Internationalis}, volume = {2015}, journal = {Urologia Internationalis}, number = {95}, publisher = {Karger}, address = {Basel}, issn = {0042-1138}, doi = {10.1159/000368419}, pages = {106 -- 113}, year = {2015}, language = {en} } @article{SchumannRoginSchneideretal.2015, author = {Schumann, Christiane and Rogin, Sabine and Schneider, Horst and Tippk{\"o}tter, Nils and Oster, J{\"u}rgen and Kampeis, Percy}, title = {Simultane Atline-Quantifizierung von Magnetpartikeln und Mikroorganismen bei einer HGMS-Filtration}, series = {Chemie Ingenieur Technik}, volume = {87}, journal = {Chemie Ingenieur Technik}, number = {1-2}, doi = {10.1002/cite.201300158}, pages = {137 -- 149}, year = {2015}, abstract = {Es wird eine neue Atline-Messmethode vorgestellt, mit der w{\"a}hrend 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 m{\"o}glich, die Trennleistung einer HGMS-Filtration zu bestimmen und einen Filterdurchbruch durch Konzentrationsanstiege im Bereich einiger µg L-1 von Magnetpartikeln im Filtrat fr{\"u}hzeitig zu detektieren, ohne dass nennenswerte Partikelmengen verloren gehen.}, language = {de} } @incollection{FrotscherGossmannRaatschenetal.2015, author = {Frotscher, Ralf and Goßmann, Matthias and Raatschen, Hans-J{\"u}rgen and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM}, series = {Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45)}, booktitle = {Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45)}, publisher = {Springer}, address = {Heidelberg}, isbn = {978-3-319-02534-6 ; 978-3-319-02535-3}, pages = {187 -- 212}, year = {2015}, abstract = {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.}, language = {en} } @inproceedings{WulfhorstMerseburgTippkoetter2015, author = {Wulfhorst, Helene and Merseburg, Johannes and Tippk{\"o}tter, Nils}, title = {Analyse von Lignocellulose mittels dynamischer Differenzkalorimetrie und Infrarot - Spektrometrie}, series = {12. Dresdner Sensor-Symposium 2015 2015-12-07 - 2015-12-09}, booktitle = {12. Dresdner Sensor-Symposium 2015 2015-12-07 - 2015-12-09}, isbn = {978-3-9813484-9-1}, doi = {10.5162/12dss2015/P6.2}, pages = {210 -- 215}, year = {2015}, language = {de} } @article{ThielMufflerTippkoetteretal.2015, author = {Thiel, Alexander and Muffler, Kai and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland}, title = {Aufarbeitung von Polyphenolen aus Weizen mittels Zeolithen am Beispiel der Ferulas{\"a}ure}, series = {Chemie IngenieurTechnik}, volume = {87}, journal = {Chemie IngenieurTechnik}, number = {1-2}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/cite.201400031}, pages = {128 -- 136}, year = {2015}, abstract = {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.}, language = {de} } @article{AlKaidyDuweHusteretal.2015, author = {Al-Kaidy, Huschyar and Duwe, Anna and Huster, Manuel and Muffler, Kai and Schlegel, Christin and Tim, Sieker and Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Biotechnology and bioprocess engineering - from the first ullmann's article to recent trends}, series = {ChemBioEng Reviews}, volume = {2}, journal = {ChemBioEng Reviews}, number = {3}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/cben.201500008}, pages = {175 -- 184}, year = {2015}, abstract = {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.}, language = {en} } @article{HendersonMclaughlinScheeretal.2015, author = {Henderson, Colin J. and Mclaughlin, Lesley A. and Scheer, Nico and Stanley, Lesley A. and Wolf, C. Roland}, title = {Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s}, series = {Molecular Pharmacology}, volume = {87}, journal = {Molecular Pharmacology}, number = {4}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-0111}, doi = {10.1124/mol.114.097394}, pages = {733 -- 739}, year = {2015}, language = {en} } @article{ScheerKapelyukhRodeetal.2015, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland}, title = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009x}, doi = {10.1124/dmd.115.065656}, pages = {1679 -- 1690}, year = {2015}, language = {en} } @article{MolinnusBaeckerSiegertetal.2015, author = {Molinnus, Denise and B{\"a}cker, Matthias and Siegert, Petra and Willenberg, H. and Poghossian, Arshak and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Detection of Adrenaline Based on Substrate Recycling Amplification}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.708}, pages = {540 -- 543}, year = {2015}, abstract = {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.}, language = {en} } @article{WiesenTippkoetterMuffleretal.2015, author = {Wiesen, Sebastian and Tippk{\"o}tter, Nils and Muffler, Kai and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland}, title = {Adsorption of fatty acids to layered double hydroxides in aqueous systems}, series = {Adsorption}, volume = {21}, journal = {Adsorption}, number = {6-7}, publisher = {Springer}, address = {Berlin}, pages = {459 -- 466}, year = {2015}, abstract = {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-.}, language = {en} } @article{HoughNalwalkDingetal.2015, author = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico}, title = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {9}, issn = {1521-009x}, doi = {10.1124/dmd.115.065490}, pages = {1326 -- 1330}, year = {2015}, language = {en} } @article{WincklerKruegerSchnitzleretal.2014, author = {Winckler, Silvia and Krueger, Rolf and Schnitzler, Thomas and Zang, Werner and Fischer, Rainer and Biselli, Manfred}, title = {A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach}, series = {Bioprocess and biosystems engineering}, volume = {37}, journal = {Bioprocess and biosystems engineering}, number = {5}, publisher = {Springer}, address = {Berlin, Heidelberg}, issn = {1615-7591 (Print) 1615-7605 (Online)}, doi = {10.1007/s00449-013-1062-8}, pages = {901 -- 912}, year = {2014}, abstract = {Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.}, language = {en} } @article{HeinzeMangPeteretal.2014, author = {Heinze, Daniel and Mang, Thomas and Peter, Karin and M{\"o}ller, Martin and Weichold, Oliver}, title = {Synthesis of low molecular weight poly(vinyl acetate) and its application as plasticizer}, series = {Journal of applied polymer science}, volume = {131}, journal = {Journal of applied polymer science}, number = {9}, publisher = {Wiley}, address = {New York}, issn = {1097-4628 (E-Journal); 0021-8995 (Print)}, doi = {10.1002/app.40226}, pages = {Article No. 40226}, year = {2014}, abstract = {Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt \%, while sheets with a thickness of 0.2-0.5 mm appear flexible already at 7.5 wt \%. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials.}, language = {en} } @article{WangDruckenmuellerElbersetal.2014, author = {Wang, Ren-Qi and Druckenm{\"u}ller, Katharina and Elbers, Gereon and Guenther, Klaus and Crou{\´e}, Jean-Philippe}, title = {Analysis of aquatic-phase natural organic matter by optimized LDI-MS method}, series = {Journal of mass spectrometry}, volume = {49}, journal = {Journal of mass spectrometry}, number = {2}, publisher = {Wiley}, address = {Bognor Regis}, issn = {1096-9888}, doi = {10.1002/jms.3321}, pages = {154 -- 160}, year = {2014}, abstract = {The composition and physiochemical properties of aquatic-phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200-1200 m/z were determined in reflectron mode. In addition, spectra of post-source-decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200-15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI-MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley \& Sons, Ltd.}, language = {en} } @article{HeineHerrmannSelmeretal.2014, author = {Heine, A. and Herrmann, G. and Selmer, Thorsten and Terwesten, F. and Buckel, W. and Reuter, K.}, title = {High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily}, series = {Proteins}, volume = {82}, journal = {Proteins}, number = {9}, publisher = {Wiley-Liss}, address = {New York}, issn = {1097-0134 (E-Journal); 0887-3585 (Print)}, doi = {10.1002/prot.24557}, pages = {2041 -- 2053}, year = {2014}, abstract = {Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 {\AA} as well as in complex with CoA at a resolution of 1.59 {\AA}. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called "hot dog fold" which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all "hot dog fold" proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041-2053. © 2014 Wiley Periodicals, Inc.}, language = {en} } @article{TakenagaBiselliSchnitzleretal.2014, author = {Takenaga, Shoko and Biselli, Manfred and Schnitzler, Thomas and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis-Menten-like kinetics for cell culturing}, series = {Physica status solidi A : Applications and materials science}, volume = {211}, journal = {Physica status solidi A : Applications and materials science}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print)}, doi = {10.1002/pssa.201330464}, pages = {1410 -- 1415}, year = {2014}, abstract = {The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17-200 mM) follows a Michaelis-Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device.}, language = {en} } @article{GuoMiyamotoWagneretal.2014, author = {Guo, Yuanyuan and Miyamoto, Ko-ichiro and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Yoshinobu, Tatsuo}, title = {Theoretical study and simulation of light-addressable potentiometric sensors}, series = {Physica status solidi (A) : applications and materials}, volume = {211}, journal = {Physica status solidi (A) : applications and materials}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0031-8965}, doi = {10.1002/pssa.201330354}, pages = {1467 -- 1472}, year = {2014}, abstract = {The light-addressable potentiometric sensor (LAPS) is a semiconductor-based potentiometric sensor using a light probe with an ability of detecting the concentration of biochemical species in a spatially resolved manner. As an important biomedical sensor, research has been conducted to improve its performance, for instance, to realize high-speed measurement. In this work, the idea of facilitating the device-level simulation, instead of using an equivalent-circuit model, is presented for detailed analysis and optimization of the performance of the LAPS. Both carrier distribution and photocurrent response have been simulated to provide new insight into both amplitude-mode and phase-mode operations of the LAPS. Various device parameters can be examined to effectively design and optimize the LAPS structures and setups for enhanced performance.}, language = {en} } @article{WhiteheadOehlschlaegerAlmajhdietal.2014, author = {Whitehead, Mark and {\"O}hlschl{\"a}ger, Peter and Almajhdi, Fahad N. and Alloza, Leonor and Marz{\´a}bal, Pablo and Meyers, Ann E. and Hitzeroth, Inga I. and Rybicki, Edward P.}, title = {Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice}, series = {BMC cancer}, journal = {BMC cancer}, number = {14:367}, publisher = {BioMed Central}, address = {London}, issn = {1471-2407}, doi = {10.1186/1471-2407-14-367}, pages = {1 -- 15}, year = {2014}, language = {en} } @article{RaueWambachGloeggleretal.2014, author = {Raue, Markus and Wambach, M. and Gl{\"o}ggler, S. and Grefen, Dana and Kaufmann, R. and Abetz, C. and Georgopanos, P. and Handge, U. A. and Mang, Thomas and Bl{\"u}mich, B. and Abetz, V.}, title = {Investigation of historical hard rubber ornaments of Charles Goodyear}, series = {Macromolecular chemistry and physics}, volume = {Vol. 215}, journal = {Macromolecular chemistry and physics}, number = {No. 3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1352}, pages = {245 -- 254}, year = {2014}, language = {en} } @article{NachtrodtTietschMostaccietal.2014, author = {Nachtrodt, Frederik and Tietsch, Wolfgang and Mostacci, Domiziano and Scherer, Ulrich W.}, title = {Set-up and first operation of a plasma oven for treatment of low level radioactive wastes}, series = {Nuclear technology and radiation protection}, volume = {29}, journal = {Nuclear technology and radiation protection}, number = {Suppl.}, publisher = {VINČA Institute of Nuclear Sciences}, address = {Belgrad}, issn = {1451-3994}, doi = {10.2298/NTRP140SS47N}, pages = {47 -- 51}, year = {2014}, language = {en} } @article{RatkeMilowLisinskietal.2014, author = {Ratke, Lorenz and Milow, Barbara and Lisinski, Susanne and Hoepfner, Sandra}, title = {On an effect of fine ceramic particles on the structure of aerogels}, series = {Microgravity science and technology}, volume = {26}, journal = {Microgravity science and technology}, publisher = {Springer Nature}, address = {Heidelberg}, issn = {0938-0108 ; 1875-0494}, doi = {10.1007/s12217-014-9380-2}, pages = {103 -- 110}, year = {2014}, language = {en} } @misc{TippkoetterSiekerWiesenetal.2014, author = {Tippk{\"o}tter, Nils and Sieker, T. and Wiesen, S. and Duwe, A. and Roth, J. and Ulber, Roland}, title = {Simultane Saccharifizierung und Fermentierung (SSF) sowie Produktion von Aceton, Butanol, Ethanol (ABE) und Dicarbons{\"a}uren aus technischer Cellulose}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450297}, pages = {1518}, year = {2014}, abstract = {Technische Cellulose wurde als m{\"o}glicher Rohstoff zur fermentativen Produktbildung untersucht. Hierf{\"u}r wird Cellulose in der Lignocellulose-Bioraffinerie hergestellt und daraus Hydrolysat gewonnen. Die Pr{\"u}fung der technischen Hydrolysate als Substrate erfolgte anhand eines breiten Spektrums an Bioprodukten, von Kraftstoffen wie Ethanolund Butanol, bis zu den Dicarbons{\"a}uren Itacon- und Bernsteins{\"a}ure. Dabei werden Bakterien, Hefen und Pilze als Produktionsorganismen eingesetzt. Die einzelnen Herstellverfahren stellen unterschiedliche Anforderungen an die Substrathandhabung. Im Fall der Ethanol- und Butanol-Gewinnung kann eine simultane Saccharifizierung und Fermentierung (SSF) durchgef{\"u}hrt werden. Aufgrund der Produkttoxizit{\"a}t erfordert die Butanol-Herstellung dabei eine In-situ-Produktabtrennung durch L{\"o}semittelimpr{\"a}gnierte Partikel. Die Herstellung der beiden Dicarbons{\"a}uren unterscheidet sich in der Sensitivit{\"a}t der verwendeten Mikroorganismen gegen{\"u}ber Inhibitoren, die in Spuren im Hydrolysat enthalten sind. Die Bernteins{\"a}urebildung mit Actinobacillussuccinogenes kann mit unbehandeltem Hydrolysat erfolgen. Dagegen erfordert die Gewinnung von Itacons{\"a}ure mit A. terreus eine Detoxifizierung des Hydrolysats. Insgesamt konnte gezeigt werden, dass s{\"a}mtliche Bioraffinerie-Hydrolysate als Substrate f{\"u}r unterschiedliche Fermentationen geeignet sind.}, language = {de} } @article{HandtkeSchroeterJuergenetal.2014, author = {Handtke, Stefan and Schroeter, Rebecca and J{\"u}rgen, Britta and Methling, Karen and Schl{\"u}ter, Rabea and Albrecht, Dirk and Hijum, Sacha A. F. T. van and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Schweder, Thomas and Hecker, Michael and Voigt, Birgit}, title = {Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress}, series = {PLOS one}, volume = {9}, journal = {PLOS one}, number = {1}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0085625}, pages = {e85625}, year = {2014}, abstract = {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.}, language = {en} } @article{KueppersSteffenHellmuthetal.2014, author = {K{\"u}ppers, Tobias and Steffen, Victoria and Hellmuth, Hendrik and O'Connell, Timothy and Bongaerts, Johannes and Maurer, Karl-Heinz and Wiechert, Wolfgang}, title = {Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer}, series = {Microbial cell factories}, volume = {13}, journal = {Microbial cell factories}, publisher = {BioMed Central}, address = {London}, issn = {1475-2859 (E-Journal)}, doi = {10.1186/1475-2859-13-46}, pages = {Article No. 46}, year = {2014}, language = {en} } @article{ScheerWolf2014, author = {Scheer, Nico and Wolf, C. Roland}, title = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications}, series = {Xenobiotica}, volume = {44}, journal = {Xenobiotica}, number = {2}, publisher = {Taylor \& Francis}, address = {Abingdon}, issn = {1366-5928}, doi = {10.3109/00498254.2013.815831}, pages = {96 -- 108}, year = {2014}, abstract = {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.}, language = {en} } @article{HoehrPaulssenBenardetal.2014, author = {Hoehr, Cornelia and Paulßen, Elisabeth and Benard, Francois and Lee, Chris Jaeil and Hou, Xinchi and Badesso, Brian and Ferguson, Simon and Miao, Qing and Yang, Hua and Buckley, Ken and Hanemaayer, Victoire and Zeisler, Stefan and Ruth, Thomas and Celler, Anna and Schaffer, Paul}, title = {⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron}, series = {Nuclear medicine and biology}, volume = {41}, journal = {Nuclear medicine and biology}, number = {5}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9614}, doi = {10.1016/j.nucmedbio.2013.12.016}, pages = {401 -- 406}, year = {2014}, abstract = {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.}, language = {en} } @article{HentschkeHagerHojdis2014, author = {Hentschke, Reinhard and Hager, Jonathan and Hojdis, Nils}, title = {Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers}, series = {Journal of Applied Polymer Science}, volume = {131}, journal = {Journal of Applied Polymer Science}, number = {18}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-4628}, doi = {10.1002/app.40806}, pages = {1 -- 9}, year = {2014}, abstract = {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.}, language = {en} } @article{SchroeterHoffmannVoigtetal.2014, author = {Schroeter, Rebecca and Hoffmann, Tamara and Voigt, Birgit and Meyer, Hanna and Bleisteiner, Monika and Muntel, Jan and J{\"u}rgen, Britta and Albrecht, Dirk and Becher, D{\"o}rte and Lalk, Michael and Evers, Stefan and Bongaerts, Johannes and Maurer, Karl-Heinz and Putzer, Harald and Hecker, Michael and Schweder, Thomas and Bremer, Erhard}, title = {Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {11}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0080956}, pages = {e80956}, year = {2014}, abstract = {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.}, language = {en} } @article{HandtkeVollandMethlingetal.2014, author = {Handtke, Stefan and Volland, Sonja and Methling, Karen and Albrecht, Dirk and Becher, D{\"o}rte and Nehls, Jenny and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Liesegang, Heiko and Voigt, Birgit and Daniel, Rolf and Hecker, Michael}, title = {Cell physiology of the biotechnological relevant bacterium Bacillus pumilus - An omics-based approach}, series = {Journal of Biotechnology}, journal = {Journal of Biotechnology}, number = {192(A)}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2014.08.028}, pages = {204 -- 214}, year = {2014}, abstract = {Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43\% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC-MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed.}, language = {en} } @article{TippkoetterDuweWiesenetal.2014, author = {Tippk{\"o}tter, Nils and Duwe, Anna-Maria and Wiesen, Sebastian and Sieker, Tim and Ulber, Roland}, title = {Enzymatic hydrolysis of beech wood lignocellulose at high solid contents and its utilization as substrate for the production of biobutanol and dicarboxylic acids}, series = {Bioresource Technology}, volume = {167}, journal = {Bioresource Technology}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.biortech.2014.06.052}, pages = {447 -- 455}, year = {2014}, abstract = {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.}, language = {en} } @article{TippkoetterWollnySucketal.2014, author = {Tippk{\"o}tter, Nils and Wollny, Steffen and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland}, title = {Recycling of spent oil bleaching earth as source of glycerol for the anaerobic production of acetone, butanol, and ethanol with Clostridium diolis and lipolytic Clostridium lundense}, series = {Engineering in Life Sciences}, volume = {14}, journal = {Engineering in Life Sciences}, number = {4}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1618-2863}, doi = {10.1002/elsc.201300113}, pages = {425 -- 432}, year = {2014}, abstract = {A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration.}, language = {en} } @misc{AlKaidyTippkoetterUlber2014, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Vorrichtung und Verfahren zur Bestimmung des Kontaktwinkels eines fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rpers [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt}, address = {M{\"u}nchen}, pages = {13 Seiten}, year = {2014}, abstract = {Die vorliegende Erfindung betrifft eine Vorrichtung und ein Verfahren zur Bestimmung des Kontaktwinkels eines fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rpers. Dieser besteht aus einem Tr{\"a}ger (1) und einer damit verbundenen, in einem Winkelbereich von mehr als 0° bis maximal 90° neigbaren Ebene (8) mit einer darin ausgebildeten Abrollbahn (9) f{\"u}r den fl{\"u}ssigen oder mit Fl{\"u}ssigkeit gef{\"u}llten K{\"o}rper. An der Ebene (8) sind mehrere Sensoren (11, 12) zur Erfassung der Rolldauer des K{\"o}rpers entlang der Rollstrecke angeordnet. Erfindungsgem{\"a}ß ist vorgesehen, dass die Einstellung des Neigungswinkels der Ebene (8) {\"u}ber ein Winkelmessger{\"a}t (10) erfolgt, wodurch ein Abrollwinkel erfassbar ist, bei dem der K{\"o}rper in Bewegung ger{\"a}t. Aus der Rolldauer, der Rollstrecke und dem Abrollwinkel wird der Kontaktwinkel des K{\"o}rpers ermittelt.}, language = {de} } @misc{WollnyAlKaidyTippkoetteretal.2014, author = {Wollny, S. and Al-Kaidy, H. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Prozessintegrierte Magnetseparation im Labormaßstab mittels High-Gradient Magnetic Separator (HGMS)}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450618}, pages = {1507}, year = {2014}, abstract = {Die Hochgradient-Magnetseparation (HGMS) stellt eine Alternative zu konventionellen Methoden der Proteinaufarbeitung wie Filtration und Chromatographie dar und dient zudem als Prozessintensivierung. Bisherige Separatoren sind f{\"u}r Anwendungen von mehreren Litern Prozessvolumina Fermentationsmedium und Gramm Magnetpartikel ausgelegt. Bei der Entwicklung und Anwendung neuartiger Magnetpartikeloberfl{\"a}chen ist die Verf{\"u}gbarkeit großer Mengen nicht gegeben. Bisherige Filterkammern erh{\"o}hen zudem den Arbeitsaufwand und verursachen gr{\"o}ßere Partikelverluste bei Sp{\"u}lvorg{\"a}ngen oder der Reinigung aufgrund der Partikeladsorption. F{\"u}r Anwendungen im Maßstab < 500 mL wird deshalb ein Miniatur-Hochgradientfilter (miniHGF) entwickelt. Das Modell wird im 3D-Drucker Makerbot Replicator 2 gefertigt und magne-isierbare Dr{\"a}hte zur Partikelabscheidung eingesetzt. Die Vergleichbarkeit mit einem etablierten Magnetseparator wird anhand der Aufnahme von Durchbruchskurven und Bestimmung der Filtereffizienz untersucht. Die Praxistauglichkeit mit kleinen Volumina wird in wiederholten Batch-Versuchen mit auf Magnetpartikeln immobilisiertem Enzym und einem kolorimetrischen Assay gepr{\"u}ft.}, language = {de} } @article{SalpatiChuChenetal.2014, author = {Salpati, Laurent and Chu, Xiaoyan and Chen, Liangfu and Prasad, Bhagwat and Dallas, Shannon and Evers, Raymond and Mamaril-Fishman, Donna and Geier, Ethan G. and Kehler, Jonathan and Kunta, Jeevan and Mezler, Mario and Laplanche, Loic and Pang, Jodie and Soars, Matthew G. and Unadkat, Jashvant D. and van Waterschoot, Robert A.B. and Yabut, Jocelyn and Schinkel, Alfred H. and Scheer, Nico and Rode, Anja}, title = {Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {8}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057976}, pages = {1301 -- 1313}, year = {2014}, abstract = {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.}, language = {en} } @misc{TippkoetterRothMoehringetal.2014, author = {Tippk{\"o}tter, Nils and Roth, J. and M{\"o}hring, M. and Wulfhorst, H. and Ulber, Roland}, title = {Verwertung von Bioraffinerie-Stoffstr{\"o}men am Beispiel von Einzellerproteinen}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450257}, pages = {1399 -- 1400}, year = {2014}, abstract = {Die Nutzung von Biomasse aus pflanzlichen Abf{\"a}llen f{\"u}r die stoffliche Verwertung r{\"u}ckt immer st{\"a}rker in den Vordergrund. Dabei ist vor allem die ganzheitliche Verwertung der Stoffstr{\"o}me von Bedeutung, da diese einen integrativen Ansatz erm{\"o}glichen. Im Rahmen dieser Arbeit wird die Produktion von Einzellerproteinen (Single-Cell Proteins, SCPs) mithilfe von unterschiedlichen Rohsubstraten dargelegt. Somit k{\"o}nnen Reststoffstr{\"o}me, die in keiner Konkurrenz zur Produktion von Lebensmitteln stehen, f{\"u}r die Herstellung von Futter- und auch Nahrungsmitteln Verwendung finden. Die zun{\"a}chst thermisch vorbehandelten Ausgangsmaterialien stammen aus forstwirtschaftlichen und gr{\"u}nen Abf{\"a}llen und erm{\"o}glichen durch eine anschließende enzymatische Hydrolyse die Freisetzung von Monosacchariden. Aus diesen erfolgt die SCP-Produktion fermentativ mithilfe der drei Modellorganismen Bakterium, Hefe und Pilz. Hierf{\"u}r wird sowohl das fl{\"u}ssige Hydrolysat als auch der feste Reststoff auf der Basis einer Feststofffermentation genutzt. Auf diese Weise ist eine vollst{\"a}ndige Verwertung der Ausgangsmaterialien m{\"o}glich. Mit den gewonnen Daten erfolgt abschließend eine Bewertung der SCPs aus nachwachsenden Rohstoffen als alternative Proteinquelle.}, language = {de} } @misc{TippkoetterDuweRaisetal.2014, author = {Tippk{\"o}tter, Nils and Duwe, Anna and Rais, Dominik and Zibek, Susanne and Zorn, H.}, title = {Optimierung und Scale-up der enzymatischen Hydrolyse inkl. Ligninabbau}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450287}, pages = {1515}, year = {2014}, abstract = {Prim{\"a}re Ziele der Hydrolyse pflanzlicher nachwachsender Rohstoffe sind m{\"o}glichst hohe Zuckerkonzentrationen f{\"u}r nachfolgende Fermentationen und eine Maximierung der Produktivit{\"a}t. Zur Optimierung dieser Prozesse wird Organosolv-aufgeschlossene Buchenholz-Cellulose verwendet. Die Hydrolyse des Faserstoffes erfolgt mithilfe von Novozymes CTec2-Enzymen. Die Hydrolysen konnten durch neue R{\"u}hrerelemente auf einen Maßstab von 1000 L {\"u}bertragen werden. Dabei konnten maximale Ausbeuten (g Glucose g -1 Glucose im Faserstoff) bis 81 g g - 1 und Konzentrationen von 152 g L -1 erreicht werden. Zurzeit k{\"o}nnen unter Einsatz eines Feststoffreaktors Cellulosefasern in einer Konzentration bis 400 g L -1 enzymatisch hydrolysiert werden. Die cellulolytischen Enzyme stoßen bei hohen Feststoffkonzentrationen an ihre Grenzen. Mit steigendem Feststoffgehalt nimmt die Hydrolyseausbeute ab. Ein Ansatz zur Steigerung der Effizienz ist der Einsatz ligninolytischer Enzyme, die Ligninreste an der Organosolv-Cellulose aufschließen k{\"o}nnen. Eine solche Verbesserung der Zug{\"a}nglichkeit f{\"u}r cellulolytische Enzyme an ihr Substrat wurde durch Kultur{\"u}berst{\"a}nde verschiedener ligninolytischer Pilze erreicht. Mit Kultur{\"u}berst{\"a}nden von Stereum sp. sind Steigerungen der Glucoseausbeuten um bis zu 30 \% m{\"o}glich.}, language = {de} } @book{Berndt2014, author = {Berndt, Heinz}, title = {Neue Kondensations-Methoden zur Synthese definierter Peptid-Derivate}, address = {Aachen}, pages = {XII, VI, 207 S. : graph. Darst.}, year = {2014}, language = {de} } @misc{TippkoetterMoehring2014, author = {Tippk{\"o}tter, Nils and M{\"o}hring, S.}, title = {Nutzung von F{\"a}ulepilzen f{\"u}r die selektive Gewinnung von Cellulose und Lignin aus nicht vorbehandelter lignocellulosehaltiger Biomasse}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450353}, pages = {1385}, year = {2014}, abstract = {Einige Arten der Braun- und Weißf{\"a}ulepilze sind in der Lage, selektiv entweder Lignin oder Cellulose im Holz abzubauen. Diese Pilze k{\"o}nnen f{\"u}r eine energiesparende Vorbehandlung lignocellulosehaltiger Biomasse f{\"u}r Bioraffinerien genutzt werden, ohne auf technisch aufw{\"a}ndige Aufschlussapparate zur{\"u}ckgreifen zu m{\"u}ssen. Weißf{\"a}ulepilze bauen bevorzugt Lignin ab, wodurch die verbleibende Cellulose leichter f{\"u}r enzymatische Hydrolysen in das Monosaccharid Glucose zug{\"a}nglich wird. Braunf{\"a}ulepilze bauen dagegen Cellulose und Hemicellulose ab. Die Auswirkungen der Behandlung von Weizenstroh mit verschiedenen Pilzarten werden zurzeit untersucht. Dabei werden die Ver{\"a}nderung der enzymatischen Hydrolysierbarkeit des Substrats sowie die gebildeten Ligninderivate bestimmt. Detaillierte Betrachtungen der Biomassever{\"a}nderung werden mithilfe spezifischer F{\"a}rbemethoden durchgef{\"u}hrt, durch die morphologische Ver{\"a}nderungen der Pflanzengewebe in der 3D-Lichtmikroskopie dargestellt werden k{\"o}nnen.}, language = {de} } @misc{HeringUlberTippkoetter2014, author = {Hering, T. and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Aktiver und passiver antimikrobieller Oberfl{\"a}chenschutz durch funktionalisierte Mikropartikel}, series = {Chemie Ingenieur Technik}, volume = {9}, journal = {Chemie Ingenieur Technik}, number = {86}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450264}, pages = {1474 -- 1475}, year = {2014}, abstract = {Mikrobielle Verunreinigungen von Oberfl{\"a}chen in technischen und medizinischen Systemen sind allgegenw{\"a}rtig. Sie basieren {\"u}blicherweise auf adsorptiven Oberfl{\"a}chenbindungen organischer Komponenten (Proteine und Fette) oder Membrankomponenten aerogener sowie wassergebundener Mikroorganismen. In laufenden Forschungsarbeiten wird eine aktive sowie passive Biomodifikation von Oberfl{\"a}chen zu deren Schutz vor Adsorption von Proteinen und Mikroorganismen verfolgt. Der antimikrobielle Schutz soll dabei sowohl durch die Mikrostrukturierung bzw. Rauheitsanpassung der Oberfl{\"a}chen durch deren Beschichtung mit Mikro-und Nanopartikeln erfolgen. Ferner werden antimikrobielle Enzyme und funktionelle Gruppen auf den Mikropartikeln gebunden, um den Oberfl{\"a}chenschutz zu verst{\"a}rken. In ersten Versuchen wurden quart{\"a}re Ammoniumverbindungen auf eigens synthetisierten superparamagnetischen Eisenoxid-Nanopartikeln (Durchmesser 10 - 30 nm) immobilisiert und die wachstumshemmende Wirkung untersucht. Erste Ergebnisse zeigten, dass eine Konzentration von 10 mg mL⁻¹ der Ammoniumverbindung in einer Wachstumshemmung des verwendeten Gram-negativen Modell-Mikroorganismus E. coli GFPmut2 resultiert. Zurzeit werden synergistisch wirkende Kombinationen von Partikeln mit Proteasen, quart{\"a}ren Ammoniumverbindungen, hydrophoben Oberfl{\"a}chen und mikrostrukturierten Oberfl{\"a}chen als antimikrobieller Schutz untersucht.}, language = {de} } @misc{DuweSchlegelTippkoetteretal.2014, author = {Duwe, A. and Schlegel, C. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Sequentielle Extraktion von Cellulose zur effizienten Nutzung der Stoffstr{\"o}me in der Holzbioraffinerie}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450308}, pages = {1400}, year = {2014}, abstract = {In der Reihe der nachwachsenden Rohstoffe besitzt Holz als erneuerbare und umweltfreundliche Ressource ein großes Potenzial. {\"U}ber 11 Mio. ha Holz, das laut der Fachagentur f{\"u}r nachwachsende Rohstoffe (FNR) auch f{\"u}r industrielle Zwecke genutzt werden kann, wuchsen im Jahr 2013 allein auf bundesdeutscher Fl{\"a}che. 56,8 Mio. m³ j{\"a}hrlicher Holzeinschlag in den letzten zehn Jahren wurde zu knapp der H{\"a}lfte stofflich und der Rest energetisch verwertet. Im Rahmen dieser Arbeit konnte auf der Basis vom Holz der Buche, die nach Fichte und Kiefer die dritth{\"a}ufigste Baumart in Deutschland ist und 15\% der deutschen Waldfl{\"a}che ausmacht, die Fraktionierung der polymeren Hauptbestandteile mit niedrigem energetischen Einsatz erreicht werden. Hierbei werden in einem nachgeschalteten Extraktionsprozess die beiden Komponenten Hemicellulose und Lignin in fl{\"u}ssiger Form von der finalen festen Cellulosefraktion abgetrennt. Die Extraktion der Hemicellulose erfolgt durch eine Liquid Hot Water (LHW)-Behandlung. Untersucht wird der katalytische Zusatz anorganischer S{\"a}uren wie H₃PO₄ und H₂SO₄. Im Hinblick auf die weitere Verwertung von Lignin zu aromatischen Synthesebausteinen kommt die Organosolv-Extraktion mit einem Ethanol/Wasser-Gemisch zum Einsatz. Von Vorteil ist die weitere Verwendung beider Stoffstr{\"o}me ohne F{\"a}llungsschritt und nachteiliger Verd{\"u}nnung der Hemicellulose.}, language = {en} } @article{WiesenTippkoetterMuffleretal.2014, author = {Wiesen, Sebastian and Tippk{\"o}tter, Nils and Muffler, Kai and Suck, Kirstin and Sohling, Ulrich and Ruf, Nils and Ulber, Roland}, title = {Adsorptive Vorbehandlung von Rohglycerin f{\"u}r die 1,3-Propandiol Fermentation mit Clostridium diolis}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {1-2}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/cite.201300080}, pages = {129 -- 135}, year = {2014}, abstract = {Bei der Gewinnung von Fetts{\"a}uren aus Pflanzen{\"o}len, z. B. zur Herstellung von Biopolymeren, oder bei der Biodiesel- und Seifenproduktion, f{\"a}llt 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 Fetts{\"a}uren identifiziert werden. Mithilfe eines adsorptiven Aufarbeitungsverfahrens ist es gelungen, die Fetts{\"a}uren zu entfernen und die Konversionseffizienz zu 1,3-Propandiol zu erh{\"o}hen.}, language = {de} } @article{AlKaidyDuweHusteretal.2014, author = {Al-Kaidy, Huschyar and Duwe, Anna and Huster, Manuel and Muffler, Kai and Schlegel, Christin and Sieker, Tim and Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Biotechnologie und Bioverfahrenstechnik - Vom ersten Ullmanns Artikel bis hin zu aktuellen Forschungsthemen}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {12}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201400083}, pages = {2215 -- 2225}, year = {2014}, abstract = {Biotechnologie und die mit ihr verbundenen technischen Prozesse pr{\"a}gen seit Jahrtausenden die Entwicklung der Menschheit. Ausgehend von empirischen Verfahren, insbesondere zur Herstellung von Lebensmitteln und t{\"a}glichen Gebrauchsg{\"u}tern, haben sich diese Disziplinen zu einem der innovativsten Zukunftsfelder entwickelt. Durch das immer detailliertere Verst{\"a}ndnis zellul{\"a}rer Vorg{\"a}nge k{\"o}nnen mittlerweile Produktionsst{\"a}mme gezielt optimiert werden. Im Zusammenspiel mit moderner Prozesstechnik k{\"o}nnen so eine Vielzahl von Bulk- und Feinchemikalien sowie Pharmazeutika effizient hergestellt werden. In diesem Artikel werden exemplarisch einige der aktuellen Trends vorgestellt.}, language = {de} } @article{PasteurTippkoetterKampeisetal.2014, author = {Pasteur, Aline and Tippk{\"o}tter, Nils and Kampeis, Percy and Ulber, Roland}, title = {Optimization of high gradient magnetic separation filter units for the purification of fermentation products}, series = {IEEE TRANSACTIONS ON MAGNETICS}, volume = {50}, journal = {IEEE TRANSACTIONS ON MAGNETICS}, number = {10}, publisher = {IEEE}, address = {New York, NY}, issn = {0018-9464}, doi = {10.1109/TMAG.2014.2325535}, pages = {Artikel 5000607}, year = {2014}, abstract = {High gradient magnetic separation (HGMS) has been established since the early 1970s. A more recent application of these systems is the use in bioprocesses. To integrate the HGMS in a fermentation process, it is necessary to optimize the separation matrix with regard to the magnetic separation characteristics and permeability of the non-magnetizable components of the fermentation broth. As part of the work presented here, a combined fluidic and magnetic force finite element model simulation was created using the software COMSOL Multiphysics and compared with separation experiments. Finally, as optimal lattice orientation of the separation matrix, a transversal rhombohedral arrangement was defined. The high suitability of the new filter matrix has been verified by separation experiments.}, language = {en} } @misc{TippkoetterWulfhorstMogueetal.2014, author = {Tippk{\"o}tter, Nils and Wulfhorst, H. and Mogue, N. and M{\"o}hring, S. and Roth, J. and Ulber, Roland}, title = {Spektrometrische Messung und Modellierung der enzymatischen Hydrolyse von Biomasse nach Organosolv- und Liquid Hot Water-Aufschl{\"u}ssen (LHW)}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450269}, pages = {1584}, year = {2014}, abstract = {In diesem Beitrag wird die NIR- und MIR-Spektrometrie in Kombination mit multivariaten Kalibrationsmodellen zur Analyse von Monosacchariden und Cellulose aus Biomasse etabliert. Spektrengemischter Standardl{\"o}sungen mit definierten Glucose- und Xylosekonzentrationen in Wasser werden im NIR-(Lambda 750, Perkin Elmer, USA) und MIR-Bereich (Spektrum 100, PerkinElmer) in Gegenwart von entweder Carboxymethylcellulose oder Grasfasern aufgenommen. Darauf basierend werden Kalibrationsmodelle (Unscrambler®, CAMO-Software AS, Norwegen) entwickelt und zur Vorhersage der Zuckerkonzentration in den Hydrolyseproben und der Celluloseanteile angewendet. Dar{\"u}ber hinaus wird die Partikelgr{\"o}ße der Rohstoffe bestimmt. Die Messergebnisse bilden die experimentelle Basis f{\"u}r die numerische Modellierung der Reaktionskinetik der enzymatischen Hydrolyse von Lignocellulose. Das Modell kombiniert die Bilanzierung der Partikelgr{\"o}ßenverteilungen mit der Multienzymkinetik. Dabei werden neben der Partikelgr{\"o}ßenverteilung und der Substratkonzentration die Zusammensetzung der Rohstoffe nach Vorbehandlung sowie die Produktinhibierung und mehrere enzymatische Aktivit{\"a}ten ber{\"u}cksichtigt. Das Modell erm{\"o}glicht es, die Partikelgr{\"o}ßenverteilungen und die Konzentrationen der Substrate und Produkte w{\"a}hrend der Hydrolyse vorherzusagen und die kinetischen Parameter im Batch- sowie im Fed-Batch-Reaktor zu bestimmen.}, language = {de} } @article{LuisierLempiaeinenScherbichleretal.2014, author = {Luisier, Rapha{\"e}lle and Lempi{\"a}inen, Harri and Scherbichler, Nina and Braeuning, Albert and Geissler, Miriam and Dubost, Valerie and M{\"u}ller, Arne and Scheer, Nico and Chibout, Salah-Dine and Hara, Hisanori and Picard, Frank and Theil, Diethilde and Couttet, Philippe and Vitobello, Antonio and Grenet, Olivier and Grasl-Kraupp, Bettina and Ellinger-Ziegelbauer, Heidrung and Thomson, John P. and Meehan, Richard R. and Elcombe, Clifford R. and Henderson, Colin J. and Wolf, C. Roland and Schwarz, Michael and Moulin, Pierre and Terranova, Remi and Moggs, Jonathan G.}, title = {Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors}, series = {Toxicological Sciences}, volume = {139}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {https://doi.org/10.1093/toxsci/kfu038}, pages = {501 -- 511}, year = {2014}, abstract = {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.}, language = {en} } @misc{TippkoetterWiesenThieletal.2014, author = {Tippk{\"o}tter, Nils and Wiesen, S. and Thiel, A. and Muffler, K. and Ulber, Roland}, title = {Biotechnologische Wertstoffgewinnung entlang der Prozessketten Gr{\"u}ner und Pflanzen{\"o}l-Bioraffinerien}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450283}, pages = {1605}, year = {2014}, abstract = {Der nachwachsende Rohstoff Raps ist in großen Mengen verf{\"u}gbar und eine Quelle f{\"u}r Biomolek{\"u}le mit hohem Wertsch{\"o}pfungspotenzial. Entwicklungen zur biotechnologischen Wertstoffgewinnung werden dabei schwerpunktm{\"a}ßig in den Bereichen Aufarbeitung und Funktionalisierung von Polyphenolen und Fetten betrieben. Bei der Verarbeitung der Pflanzenmaterialien werden dabei insbesondere Verfahren zur adsorptiven Aufreinigung und Auftrennung mittels Materialien mit modifizierten Bleicherden und anderen organischen oder anorganischen Adsorbentien untersucht. Ferner wurden f{\"u}r die Aufreinigung von Polyphenolen adsorptive sowie extraktive Prozesse entwickelt. Bei den Entwicklungen wird ber{\"u}cksichtigt, dass Bioraffinerien auf eine fortw{\"a}hrende Gew{\"a}hrleistung eines hohen Produktions- bzw. Lieferbedarfs nachwachsender Rohstoffe angewiesen sind. Somit werden Optionen dezentraler regionaler Vorbehandlungs- und Wertsch{\"o}pfungsketten in der N{\"a}he landwirtschaftlicher Betriebe einbezogen. Neben neuen Aufreinigungsverfahren werden mikrobielle und enzymatische Prozesse zur wertsteigernden Umsetzung von Glycerin, Polyphenolen und Zuckermonomeren vorgestellt sowie Limitierungen nachwachsender Rohstoffe der 2. Generation diskutiert.}, language = {de} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {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.}, language = {en} } @misc{TippkoetterWasserscheid2014, author = {Tippk{\"o}tter, Nils and Wasserscheid, P.}, title = {Rapid-Prototyping-Strukturen f{\"u}r ressourceneffiziente Prozesse in Chemie und Biotechnologie}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450451}, pages = {1369 -- 1370}, year = {2014}, abstract = {Die Teilefertigung durch Rapid Prototyping (RP) verk{\"u}rzt den Weg von der Idee bis zum Produkt, wobei unter anderem Optimierungszyklen in geringer Zeit durchlaufen werden k{\"o}nnen. Ferner er{\"o}ffnen neue Entwicklungen in diesem Bereich die M{\"o}glichkeit individueller Produktionsverfahren. Im Unterschied zur klassischen Fertigung von Prototypen wird beim RP mit additiver Schichtfertigung (Additive Layer Manufacturing, ALM) gearbeitet. Je nach Methode werden Fl{\"u}ssigkeiten oder Pulver nach Vorgaben eines 3D-Computermodells sequentiell aufgetragen. Diese Verfahren existieren seit ca. 25 Jahren, jedoch sind seit kurzem ausgesprochen g{\"u}nstige Ger{\"a}te verf{\"u}gbar, die Objekte mit Genauigkeiten bis 20 lm fertigen k{\"o}nnen. Das RP hat in klinischen Anwendungsgebieten bzw. im Bereich des Tissue Engineering bereits vielfach Einzug gefunden. Aber auch chemisch-biotechnologische Entwicklungen k{\"o}nnen von den Verfahren profitieren. So wurden Mikrofluidiksysteme und Bioreaktoren bereits erfolgreich durch RP gefertigt. Durch ALM ist ebenso die Herstellung von Reaktionseinheiten aus biokompatiblen Materialien wie ionotropen Gelen m{\"o}glich. Ferner sind sehr komplexe Strukturierungen von Oberfl{\"a}chen im Nanometerbereich realisierbar, die f{\"u}r die Auftragung heterogener Katalysatoren oder auch Mikroorganismen eingesetzt werden k{\"o}nnen. Auch der Bereich Reaktoren- und Apparatebau kann von den Fortschritten in der additiven Fertigung profitieren. Verfahren wie selektives Laser- oder Elektronenstrahlschmelzen erlauben es, metallische Komponenten in nahezu beliebigen Geometrien zu fertigen. Somit k{\"o}nnen Strukturen verwirklicht werden, die mit konventionellen Fertigungstechniken nur sehr schwer oder {\"u}berhauptnicht herstellbar w{\"a}ren. Durch Anwendung von rechnergest{\"u}tzter Modellierung k{\"o}nnen optimale Strukturen identifiziert und additiv gefertigt werden. Eine anschließende katalytische Funktionalisierung der Oberfl{\"a}che erm{\"o}glicht die Herstellung strukturierter Reaktoren mit maßgeschneiderten Eigenschaften.}, language = {de} } @misc{HeringPasteurWollnyetal.2014, author = {Hering, T. and Pasteur, A. and Wollny, S. and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Magnetische Separation von Gold-Nanopartikeln zur Glucons{\"a}ure-Produktion durch Hochgradient-Magnetseparation im Labormaßstab}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450265}, pages = {1501}, year = {2014}, abstract = {Bei der Verarbeitung nachwachsender Rohstoffe entsteht aus Cellulose oder St{\"a}rke u. a. das wichtige Produkt Glucose. Diese niedermolekulare Kohlenhydratquelle wird {\"u}blicherweise als Substrat f{\"u}r biotechnologische und chemische Synthesen verwendet. Ein wirtschaftlich interessantes Oxidationsprodukt der Glucose ist Glucons{\"a}ure, die beispielsweise als Lebensmittelzusatzstoff (E 574), in der Medizin und Metallindustrie Verwendung findet. Die Umsetzung des Monosaccharids zu Glucons{\"a}ure erfolgt entweder durch mikrobielle Fermentation oder der Oxidation an heterogenen Katalysatoren. Die Zielsetzung der Studie ist die Untersuchung der Glucoseoxidation an magnetisierbaren Gold-Nanopartikeln unter nachfolgender Bypass-Separation des Katalysators mittels einer neuen Mini-HGMS-Einheit (Hochgradient-Magnetseparation). Dieser Filtertyp erm{\"o}glicht die selektive Trennung magnetischer Partikel aus Suspensionen mit hohem Feststoffgehalt oder Viskosit{\"a}t. Erste Ergebnisse zeigen eine Beladungskapazit{\"a}t des selbstkonstruierten Mini-HGMS von 550 mg goldbeschichteter magnetisierbarer Nanopartikel. Die Oxidation erfolgt bei einem pH-Wertvon 9, bei 40 °C und mit 100 mM Glucose in einem begasten R{\"u}hrkesselreaktor. Das System soll zuk{\"u}nftig zum Katalysatorrecycling von hochviskosen und Feststoffbelasteten Produktstr{\"o}men aus Bioraffinerien eingesetzt werden.}, language = {de} } @misc{DuweSiekerTippkoetteretal.2014, author = {Duwe, A. and Sieker, T. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Grasssilage als Substrat zur fermentativen Produktion organischer S{\"a}uren}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450345}, pages = {1400}, year = {2014}, abstract = {Der zunehmende Bedarf an fossilen Rohstoffen bei gleichzeitig abnehmender Versorgungssicherheit f{\"u}hrt zu einer intensiven Suche nach erneuerbaren Ressourcen. Ein vielversprechendes Ausgangsmaterial mit einer weltweiten Verf{\"u}gbarkeit stellt Gras dar. In 2012 wurden in Deutschland 33 Millionen Tonnen (Heugewicht) Gras auf 4,82 Millionen Hektar Ackerland produziert, davon wurden 60,5 \% siliert. Durch die Silierung kann Gras als Substrat zeitlich uneingeschr{\"a}nkt verf{\"u}gbar sein, ohne dem Risiko des schnellen Verderbs ausgesetzt zu sein. Eine Schl{\"u}sselrolle im Rahmen des Silierprozesses nimmt die Produktion von Milchs{\"a}ure ein. Milchs{\"a}ure ist einbedeutendes biotechnologisches Produkt f{\"u}r die Lebensmittel- und die chemische Industrie. Im Rahmen dieser Arbeit wird die vollst{\"a}ndige Umwandlung der fermentierbaren Zucker in der Silage zu Milchs{\"a}ure angestrebt, um die maximale Ausbeute der organischen S{\"a}ure zu erreichen. Im ersten Verfahrensschritt wird die Silage gepresst und der erhaltene Presskuchen einer Liquid-Hot-Water-Behandlung unterzogen. Durch diese einfache Vorbehandlung k{\"o}nnen hohe Glucoseausbeuten im nachfolgenden SSF-Schritt bei gleichzeitig geringem Enzymeinsatz und Chemikalienverbrauch realisiert werden. Zur Aufreinigung der Milchs{\"a}ure wurden extraktive und chromatographische Methoden untersucht.}, language = {de} } @misc{StadtmuellerTippkoetterUlber2014, author = {Stadtm{\"u}ller, R. and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Produktion von einzelstr{\"a}ngigen DNA-Makronukleotiden}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450372}, pages = {1403}, year = {2014}, abstract = {In der Biotechnologie stellt Einzelstrang-DNA (ssDNA) eine Schl{\"u}sselrolle dar und fungiert z. B. als Baustein f{\"u}r die nanoskalige Feinmechanik oder als Affinit{\"a}tsligand, ein sog. Aptamer. Hinsichtlich der industriellen Verwendung bieten Aptamere im Vergleich zu Antik{\"o}rpern viele Vorteile, wie z. B. eine gute Renaturierung bzw. die Selektion f{\"u}r cytotoxische Molek{\"u}le. Aktuell w{\"a}chst die Nachfrage f{\"u}r chim{\"a}re Aptamere von bis zu 200 n, um die simultane Bindung bzw. die Modifikation mehrerer Molek{\"u}le zu realisieren. Bis heute wird ssDNA mittels einer sequentiellen Synthese hergestellt, die eine Effizienz von ca. 99,5 \% je Zyklus und bereits bei einer Produktl{\"a}nge von 100 n nur noc hAusbeuten von max. 60 \% zeigt. Um dem Bedarf an ssDNA im Bereich > 100 n zu entsprechen, wurden zwei enzymatische Verfahren zur Produktion dieser Makronukleotide entworfen. Die erste Technik basiert auf einerFestphasen-PCR und erm{\"o}glicht sowohlein Primer- als auch ein Templatrecycling. Das zweite Verfahren beruht auf einer Plasmidbasierten In-vivo-Amplifikation, der sog. AptaGENE®-Technologie. In einer einzigen Klonierung werden bis zu 100 Kopien des Monomers in einen Vektor kloniert. Nach einer Transformation folgt der regul{\"a}re Produktionsprozess in Form einer Kultivierung, Plasmidpr{\"a}paration und sequenziellen Aufarbeitung von bis zu 6 · 10¹⁵ Makronukleotiden pro Milliliter Fermentationsvolumen.}, language = {de} } @misc{AlKaidyTippkoetterKaiseretal.2014, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils and Kaiser, P. and Wollny, S. and Ulber, Roland}, title = {Aufreinigung von Cytochrom P450BMP mittels magnetischer Partikel und die enzymatische Synthese von 9, 10-Dihydroxystearins{\"a}ure}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450420}, pages = {1420}, year = {2014}, abstract = {Cytochrom P450 sind H{\"a}m-Proteine, die zur Enzymklasse der Oxidoreduktasen (EC 1.14.xy) geh{\"o}ren. Eine wichtige Reaktion ist die Hydroxylierung nichtaktivierter C-H-Bindungen, die in technischen Systemen von großem Interesse ist. Durch die Verwendung von M-IDA-2-Partikeln ist eine direkte Aufreinigung mit gleichzeitiger Immobilisierung und die Applikation der Enzyme aus dem Zelllysat m{\"o}glich. Damit ist das Verfahren mehr als f{\"u}nf Stunden schneller als die konventionelle Chromatographie und mehr als 80 \% der Aufreinigungszeit wird gespart. Mit dem isolierten nativen Enzym konnte die Plattformchemikalie 9,10-Dihydroxystearins{\"a}ure aus {\"O}ls{\"a}ure hergestellt werden. Unter anderem f{\"u}r die Kunststoffindustrie k{\"o}nnen aus diesem Produkt wichtige Monomere wie z. B. Azelains{\"a}ure hergestellt werden. Die Bildung des Produkts erfolgt in einem zweiphasigen Reaktionssystem an der Grenzfl{\"a}che zwischen dem {\"O}l und der w{\"a}ssrigen Phase als Feststoff. Um das immobilisierte Enzym aktiv in die obere Phase zu transportieren, wurde eine neue magnetische Mischvorrichtung entwickelt. Das Reaktionsprodukt wurde mit NMR, GC-MS und HPLC-MS analysiert und mit einem chemisch synthetisierten Standard von 9,10-Dihydroxystearins{\"a}ure verglichen. Derzeit werden Studien des immobilisierten H{\"a}ms des Enzyms durchgef{\"u}hrt.}, language = {de} } @misc{AlKaidyUlberTippkoetter2014, author = {Al-Kaidy, Huschyar and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Eine Plattform-Technologie f{\"u}r die automatisierte Reaktionsf{\"u}hrung in magnetisierbaren mikrofluidischen Tropfen}, series = {Chemie Ingenieur Technik}, volume = {86}, journal = {Chemie Ingenieur Technik}, number = {9}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0009-286X}, doi = {10.1002/cite.201450424}, pages = {1419 -- 1420}, year = {2014}, abstract = {{\"U}blicherweise werden biotechnologische Reaktionssysteme im mikrofluidischen Maßstab in vorstrukturierten Bauteilen oder mit auf Wellplatten basierenden Robotersystemen realisiert. In dem hier vorgestellten System werden chemische oder biologische Reaktionen mit magnetischen Mikroreaktoren (MR) durchgef{\"u}hrt, bei denen hydrophobe magnetische Mikropartikel einen w{\"a}ssrigen Kern umschließen. Solche MR bieten eine gute Kontrolle der Reaktionsbedingungen, eine verbesserte Sicherheit und Portabilit{\"a}t. Die neue Plattformtechnologie erm{\"o}glicht die zweidimensionale Bewegung der magnetischen MR auf einer planaren Ebene. Oberhalb oder unterhalb der Plattform werden Magnetfeldgradienten zum Manipulieren und Bewegen eines oder mehrerer magnetischer MR erzeugt. Die optimal auf die MR wirkenden magnetischen Kr{\"a}fte werden experimentell ermittelt und simuliert. Die Aktivierung der Magnetfelder wird automatisiert durch elektrische Spulen mit Eisenkern bzw. Neodymmagnet gesteuert. Angewendet wurde das System beim reversiblen {\"O}ffnen von MR, um z. B. Reaktionspartner in den w{\"a}ssrigen Kern zu injizieren oder Proben zu entnehmen. Ferner wurde Lac-case A und b-Glucosidase auf einer Quarzglasoberfl{\"a}che immobilisiert und mit einem MR zum Reagieren gebracht. Weiterhin wurden MR fusioniert und so ein w{\"a}ssriger Kern bestehend aus Laccase mit einem aus dem entsprechenden Substrat Syringaldazin vereint.}, language = {de} } @inproceedings{AlKaidyUlberTippkoetter2014, author = {Al-Kaidy, Huschyar and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {A platform technology for the automated reaction control in magnetizable micro-fluidic droplets}, series = {Biomaterials - made in bioreactors : book of abstracts, May 26 - 28, 2014, Radisson Blu Park Hotel and Conference Dentre, Radebeul, Germany}, booktitle = {Biomaterials - made in bioreactors : book of abstracts, May 26 - 28, 2014, Radisson Blu Park Hotel and Conference Dentre, Radebeul, Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {21 -- 22}, year = {2014}, language = {en} }