@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} } @inproceedings{AlKaidyUlberTippkoetter2014, author = {Al-Kaidy, H. 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} } @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{AlKaidyUlberTippkoetter2014, author = {Al-Kaidy, H. 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} } @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} } @misc{AlKaidyTippkoetterKaiseretal.2014, author = {Al-Kaidy, H. 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} } @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} }