TY - JOUR A1 - Henken, F. E. A1 - Oosterhuis, K. A1 - Öhlschläger, Peter A1 - Bosch, L. A1 - Hooijberg, E. A1 - Haanen, J. B. A. G. A1 - Steenbergen, R. D. M. T1 - Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7 JF - Vaccine N2 - Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies. Y1 - 2012 U6 - http://dx.doi.org/10.1016/j.vaccine.2012.04.013 SN - 0264-410X VL - 30 IS - 28 SP - 4259 EP - 4266 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Immel, Timo A1 - Grützke, Martin A1 - Späte, Anne-Katrin A1 - Groth, Ulrich A1 - Öhlschläger, Peter A1 - Huhn, Thomas T1 - Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy JF - Chemical Communications N2 - Chelate stabilization of a titanium(IV)–salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model. Y1 - 2012 U6 - http://dx.doi.org/10.1039/C2CC31624B SN - 1364-548X VL - 48 IS - 46 SP - 5790 EP - 5792 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Kong, Shushu A1 - Arciszewski, Pawel A1 - Wielbalck, Swantje A1 - Abram, Ulrich T1 - Aryl and NHC Compounds of Technetium and Rhenium JF - Journal of the American Chemical Society N2 - Air- and water-stable phenyl complexes with nitridotechnetium(V) cores can be prepared by straightforward procedures. [TcNPh2(PPh3)2] is formed by the reaction of [TcNCl2(PPh3)2] with PhLi. The analogous N-heterocyclic carbene (NHC) compound [TcNPh2(HLPh)2], where HLPh is 1,3,4-triphenyl-1,2,4-triazol-5-ylidene, is available from (NBu4)[TcNCl4] and HLPh or its methoxo-protected form. The latter compound allows the comparison of different Tc–C bonds within one compound. Surprisingly, the Tc chemistry with such NHCs does not resemble that of corresponding Re complexes, where CH activation and orthometalation dominate. Y1 - 2012 U6 - http://dx.doi.org/10.1021/ja3033718 SN - 1520-5126 VL - 134 IS - 22 SP - 9118 EP - 9121 PB - ACS Publications CY - Washington, DC ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Ngyugen, Hung Huy A1 - Kahlcke, Nils A1 - Deflon, Victor M. A1 - Abram, Ulrich T1 - Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines JF - Polyhedron N2 - N,N-Dialkylamino(thiocarbonyl)-N′-picolylbenzamidines react with (NEt4)2[M(CO)3X3] (M = Re, X = Br; M = Tc, X = Cl) under formation of neutral [M(CO)3L] complexes in high yields. The monoanionic NNS ligands bind in a facial coordination mode and can readily be modified at the (CS)NR1R2 moiety. The complexes [99Tc(CO)3(LPyMor)] and [Re(CO)3(L)] (L = LPyMor, LPyEt) were characterized by X-ray diffraction. Reactions of [99mTc(CO)3(H2O)3]+ with the N′-thiocarbamoylpicolylbenzamidines give the corresponding 99mTc complexes. The ester group in HLPyCOOEt allows linkage between biomolecules and the metal core. Y1 - 2012 U6 - http://dx.doi.org/10.1016/j.poly.2012.04.008 SN - 0277-5387 VL - 40 IS - 1 SP - 153 EP - 158 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Balimane, Praveen A1 - Hayward, Michael D. A1 - Buechel, Sandra A1 - Kauselmann, Gunther A1 - Wolf, C. Roland T1 - Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line JF - Drug Metabolism and Disposition N2 - The multidrug resistance protein (MRP) 2 is predominantly expressed in liver, intestine, and kidney, where it plays an important role in the excretion of a range of drugs and their metabolites or endogenous compounds into bile, feces, and urine. Mrp knockout [Mrp2(−/−)] mice have been used recently to study the role of MRP2 in drug disposition. Here, we describe the first generation and initial characterization of a mouse line humanized for MRP2 (huMRP2), which is nulled for the mouse Mrp2 gene and expresses the human transporter in the organs and cell types where MRP2 is normally expressed. Analysis of the mRNA expression for selected cytochrome P450 and transporter genes revealed no major changes in huMRP2 mice compared with wild-type controls. We show that human MRP2 is able to compensate functionally for the loss of the mouse transporter as demonstrated by comparable bilirubin levels in the humanized mice and wild-type controls, in contrast to the hyperbilirubinemia phenotype that is observed in MRP2(−/−) mice. The huMRP2 mouse provides a model to study the role of the human transporter in drug disposition and in assessing the in vivo consequences of inhibiting this transporter by compounds interacting with human MRP2. Y1 - 2012 U6 - http://dx.doi.org/10.1124/dmd.112.047605 SN - 1521-0111 VL - 40 IS - 11 SP - 2212 EP - 2218 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Buechel, Sandra A1 - Wolf, C. Roland T1 - Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines JF - Molecular Pharmacology N2 - Compared with rodents and many other animal species, the human cytochrome P450 (P450) Cyp2c gene cluster varies significantly in the multiplicity of functional genes and in the substrate specificity of its enzymes. As a consequence, the use of wild-type animal models to predict the role of human CYP2C enzymes in drug metabolism and drug-drug interactions is limited. Within the human CYP2C cluster CYP2C9 is of particular importance, because it is one of the most abundant P450 enzymes in human liver, and it is involved in the metabolism of a wide variety of important drugs and environmental chemicals. To investigate the in vivo functions of cytochrome P450 Cyp2c genes and to establish a model for studying the functions of CYP2C9 in vivo, we have generated a mouse model with a deletion of the murine Cyp2c gene cluster and a corresponding humanized model expressing CYP2C9 specifically in the liver. Despite the high number of functional genes in the mouse Cyp2c cluster and the reported roles of some of these proteins in different biological processes, mice deleted for Cyp2c genes were viable and fertile but showed certain phenotypic alterations in the liver. The expression of CYP2C9 in the liver also resulted in viable animals active in the metabolism and disposition of a number of CYP2C9 substrates. These mouse lines provide a powerful tool for studying the role of Cyp2c genes and of CYP2C9 in particular in drug disposition and as a factor in drug-drug interaction. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.112.080036 SN - 1521-0111 VL - 82 IS - 6 SP - 1022 EP - 1029 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Lempiäinen, Harri A1 - Couttet, Philippe A1 - Bolognani, Federico A1 - Müller, Arne A1 - Dubost, Valérie A1 - Luisier, Raphaëlle A1 - Rio-Espinola, Alberto del A1 - Vitry, Veronique A1 - Unterberger, Elif B. A1 - Thomson, John P. A1 - Treindl, Fridolin A1 - Metzger, Ute A1 - Wrzodek, Clemens A1 - Hahne, Florian A1 - Zollinger, Tulipan A1 - Brasa, Sarah A1 - Kalteis, Magdalena A1 - Marcellin, Magali A1 - Giudicelli, Fanny A1 - Braeuning, Albert A1 - Morawiec, Laurent A1 - Zamurovic, Natasa A1 - Längle, Ulrich A1 - Scheer, Nico A1 - Schübeler, Dirk A1 - Goodman, Jay A1 - Chibout, Salah-Dine A1 - Marlowe, Jennifer A1 - Theil, Dietlinde A1 - Heard, David J. A1 - Grenet, Olivier A1 - Zell, Andreas A1 - Templin, Markus F. A1 - Meehan, Richard R. A1 - Wolf, Roland C. A1 - Elcombe, Clifford R. A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Rémi A1 - Moggs, Jonathan G. T1 - Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion JF - Toxicological Sciences N2 - The molecular events during nongenotoxic carcinogenesis and their temporal order are poorly understood but thought to include long-lasting perturbations of gene expression. Here, we have investigated the temporal sequence of molecular and pathological perturbations at early stages of phenobarbital (PB) mediated liver tumor promotion in vivo. Molecular profiling (mRNA, microRNA [miRNA], DNA methylation, and proteins) of mouse liver during 13 weeks of PB treatment revealed progressive increases in hepatic expression of long noncoding RNAs and miRNAs originating from the Dlk1-Dio3 imprinted gene cluster, a locus that has recently been associated with stem cell pluripotency in mice and various neoplasms in humans. PB induction of the Dlk1-Dio3 cluster noncoding RNA (ncRNA) Meg3 was localized to glutamine synthetase-positive hypertrophic perivenous hepatocytes, sug- gesting a role for β-catenin signaling in the dysregulation of Dlk1-Dio3 ncRNAs. The carcinogenic relevance of Dlk1-Dio3 locus ncRNA induction was further supported by in vivo genetic dependence on constitutive androstane receptor and β-catenin pathways. Our data identify Dlk1-Dio3 ncRNAs as novel candidate early biomarkers for mouse liver tumor promotion and provide new opportunities for assessing the carcinogenic potential of novel compounds. Y1 - 2012 U6 - http://dx.doi.org/10.1093/toxsci/kfs303 SN - 1094-2025 VL - 131 IS - 2 SP - 375 EP - 386 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - McEwan, Jillian A1 - Beuger, Vincent A1 - Stanley, Lesley A. A1 - Rode, Anja A1 - Wolf, C. Roland T1 - Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines JF - Molecular Pharmacology N2 - The highly polymorphic human cytochrome P450 2D6 enzyme is involved in the metabolism of up to 25% of all marketed drugs and accounts for significant individual differences in response to CYP2D6 substrates. Because of the differences in the multiplicity and substrate specificity of CYP2D family members among species, it is difficult to predict pathways of human CYP2D6-dependent drug metabolism on the basis of animal studies. To create animal models that reflect the human situation more closely and that allow an in vivo assessment of the consequences of differential CYP2D6 drug metabolism, we have developed a novel straightforward approach to delete the entire murine Cyp2d gene cluster and replace it with allelic variants of human CYP2D6. By using this approach, we have generated mouse lines expressing the two frequent human protein isoforms CYP2D6.1 and CYP2D6.2 and an as yet undescribed variant of this enzyme, as well as a Cyp2d cluster knockout mouse. We demonstrate that the various transgenic mouse lines cover a wide spectrum of different human CYP2D6 metabolizer phenotypes. The novel humanization strategy described here provides a robust approach for the expression of different CYP2D6 allelic variants in transgenic mice and thus can help to evaluate potential CYP2D6-dependent interindividual differences in drug response in the context of personalized medicine. Y1 - 2012 U6 - http://dx.doi.org/10.1124/mol.111.075192 SN - 1521-0111 VL - 81 IS - 1 SP - 63 EP - 72 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Schiffels, Johannes A1 - Pinkenburg, Olaf A1 - Schelden, Maximilian A1 - Aboulnaga, El-Hussiny A. A. A1 - Baumann, Marcus A1 - Selmer, Thorsten T1 - An innovative cloning platform enables large-scale production and maturation of an oxygen-tolerant [NiFe]-hydrogenase from cupriavidus necator in Escherichia coli JF - PLOS one. 2013 Y1 - 2013 U6 - http://dx.doi.org/10.1371/journal.pone.0068812 SN - 1932-6203 PB - Public Library of Science CY - San Francisco, California ER - TY - JOUR A1 - Abulnaga, El-Hussiny A1 - Pinkenburg, Olaf A1 - Schiffels, Johannes A1 - E-Refai, Ahmed A1 - Buckel, Wolfgang A1 - Selmer, Thorsten T1 - Effect of an Oxygen-Tolerant Bifurcating Butyryl Coenzyme A Dehydrogenase/Electron-Transferring Flavoprotein Complex from Clostridium difficile on Butyrate Production in Escherichia coli JF - Journal of bacteriology Y1 - 2013 SN - 1098-5530 [E-Journal] SN - 0021-9193 [Print] VL - 195 IS - 16 SP - 3704 EP - 3713 ER - TY - JOUR A1 - Scheele, Sandra A1 - Oertel, Dan A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Hellmuth, Hendrik A1 - Maurer, Karl-Heinz A1 - Bott, Michael A1 - Freudl, Roland T1 - Secretory production of an FAD cofactor-containing cytosolic enzyme (sorbitol–xylitol oxidase from Streptomyces coelicolor) using the twin-arginine translocation (Tat) pathway of Corynebacterium glutamicum JF - Microbial biotechnology Y1 - 2013 SN - 1751-7915 SP - 202 EP - 206 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Wilming, Anja A1 - Begemann, Jens A1 - Kuhne, Stefan A1 - Regestein, Lars A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Maurer, Karl-Heinz A1 - Büchs, Jochen T1 - Metabolic studies of γ-polyglutamic acid production in Bacillus licheniformis by small-scale continuous cultivations JF - Biochemical engineering journal Y1 - 2013 SN - 1873-295X (E-Journal); 1369-703X (Print) VL - Vol. 73 SP - 29 EP - 37 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Voigt, Birgit A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Schweder, Thomas A1 - Hecker, Michael T1 - The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon JF - Proteomics Y1 - 2013 SN - 1615-9861 (E-Journal); 1615-9853 (Print) VL - Vol. 13 IS - Iss. 14 SP - 2140 EP - 2146 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Rachinger, Michael A1 - Bauch, Melanie A1 - Strittmatter, Axel A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Maurer, Karl-Heinz A1 - Daniel, Rolf A1 - Liebl, Wolfgang A1 - Liesegang, Heiko A1 - Ehrenreich, Armin T1 - Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis JF - Journal of biotechnology Y1 - 2013 SN - 1873-4863 (E-Journal); 0168-1656 (Print) VL - Vol. 164 IS - Iss. 4 SP - 365 EP - 369 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Wiegand, Sandra A1 - Dietrich, Sascha A1 - Hertel, Robert A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Volland, Sonja A1 - Daniel, Rolf A1 - Liesegang, Heiko T1 - RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation JF - BMC genomics Y1 - 2013 SN - 1471-2164 VL - Vol. 14 SP - 667 PB - BioMed Central CY - London ER - TY - JOUR A1 - Dutta, Suryendu A1 - Hartkopf-Fröder, Christoph A1 - Witte, Karin A1 - Brocke, Rainer A1 - Mann, Ulrich T1 - Molecular characterization of fossil palynomorphs by transmission micro-FTIR spectroscopy: implications for hydrocarbon source evaluation JF - International journal of coal geology Y1 - 2013 SN - 1872-7840 (E-Journal); 0166-5162 (Print) VL - Vol. 115 SP - 13 EP - 23 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Takenaga, Shoko A1 - Herrera, Cony F. A1 - Werner, Frederik A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Schöning, Michael Josef A1 - Öhlschläger, Peter A1 - Wagner, Torsten T1 - Detection of the metabolic activity of cells by differential measurements based on a single light-addressable potentiometric sensor chip T2 - 11. Dresdner Sensor-Symposium : 9.-11.12.2013 Y1 - 2013 SN - 978-3-9813484-5-3 SP - 63 EP - 67 ER - TY - JOUR A1 - Martinez, Ronny A1 - Jakob, Felix A1 - Tu, Ran A1 - Siegert, Petra A1 - Maurer, Karl-Heinz A1 - Schwaneberg, Ulrich T1 - Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution JF - Biotechnology and bioengineering Y1 - 2013 SN - 1097-0290 (E-Journal); 0006-3592 (Print); 0368-1467 (Print) VL - Vol. 110 IS - Iss. 3 SP - 711 EP - 720 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Jakob, Felix A1 - Martinez, Ronny A1 - Mandawe, John A1 - Hellmuth, Hendrik A1 - Siegert, Petra A1 - Maurer, Karl-Heinz A1 - Schwaneberg, Ulrich T1 - Surface charge engineering of a Bacillus gibsonii subtilisin protease JF - Applied microbiology and biotechnology Y1 - 2013 SN - 1432-0614 (E-Journal); 0171-1741 (Print); 0175-7598 (Print); 0340-2118 (Print) VL - Vol. 97 IS - Iss. 15 SP - 6793 EP - 6802 PB - Springer CY - Berlin ER - TY - JOUR A1 - Scheer, Nico A1 - Snaith, Mike A1 - Wolf, C. Roland A1 - Seibler, Jost T1 - Generation and utility of genetically humanized mouse models JF - Drug Discovery Today Y1 - 2013 U6 - http://dx.doi.org/10.1016/j.drudis.2013.07.007 SN - 1359-6446 VL - Vol 18 IS - 23-24 SP - 1200 EP - 1211 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bouwman, Peter A1 - Gulden, Hanneke van der A1 - Heijden, Ingrid van der A1 - Drost, Rinske A1 - Klijn, Christiaan N. A1 - Prasetyanti, Pramudita A1 - Pieterse, Mark A1 - Wientjens, Ellen A1 - Seibler, Jost A1 - Hogervorst, Frank B. L. A1 - Jonkers, Jos T1 - A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants JF - Cancer Discovery Y1 - 2013 U6 - http://dx.doi.org/10.1158/2159-8290.CD-13-0094 SN - 2159-8290 IS - 3 SP - 1142 EP - 1152 ER - TY - JOUR A1 - Michalak, Ewa Malgorzata A1 - Nacerddine, Karim A1 - Pietersen, Alexandra A1 - Beuger, Vincent A1 - Pawlitzky, Inka A1 - Cornelissen-Steijger, Paulien A1 - Wientjens, Ellen A1 - Tanger, Ellen A1 - Seibler, Jost A1 - Lohuizen, Maarten van A1 - Jonkers, Jos T1 - Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool JF - Stem Cells Y1 - 2013 U6 - http://dx.doi.org/10.1002/stem.1437 SN - 1549-4918 VL - Vol 31 IS - 9 SP - 1910 EP - 1920 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Gebeshuber, Christoph A. A1 - Kornauth, Christoph A1 - Dong, Lihua A1 - Sierig, Ralph A1 - Seibler, Jost A1 - Reiss, Martina A1 - Tauber, Stefanie A1 - Bilban, Martin A1 - Wang, Shijun A1 - Kain, Renate A1 - Böhmig, Georg A. A1 - Moeller, Marcus J. A1 - Gröne, Hermann-Josef A1 - Englert, Christoph A1 - Martinez, Javier A1 - Kerjaschki, Dontscho T1 - Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1 JF - Nature Medicine Y1 - 2013 U6 - http://dx.doi.org/10.1038/nm.3142 SN - 1078-8956 VL - 19 IS - 4 SP - 481 EP - 487 ER - TY - JOUR A1 - Kornfeld, Jan-Wilhelm A1 - Baitzel, Catherina A1 - Könner, A. Christine A1 - Nicholls, Hayley T. A1 - Vogt, Merly C. A1 - Herrmanns, Karolin A1 - Scheja, Ludger A1 - Haumaitre, Cécile A1 - Wolf, Anna M. A1 - Knippschild, Uwe A1 - Seibler, Jost A1 - Cereghini, Silvia A1 - Heeren, Joerg A1 - Stoffel, Markus A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b JF - Nature Y1 - 2013 SN - 0028-0836 U6 - http://dx.doi.org/10.1038/nature11793 VL - 494 IS - 7435 SP - 111 EP - 115 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Wiegand, Sandra A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Hecker, Michael A1 - Daniel, Rolf A1 - Liesegang, Heiko T1 - Fermentation stage-dependent adaptations of Bacillus licheniformis during enzyme production JF - Microbial Cell Factories Y1 - 2013 U6 - http://dx.doi.org/10.1186/1475-2859-12-120 SN - 1475-2859 VL - 12 SP - 120 PB - Biomed Central CY - London ER - TY - JOUR A1 - Thiel, Alexander A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - New zeolite adsorbents for downstream processing of polyphenols from renewable resources JF - Engineering in Life Sciences N2 - Commercial materials with polyvinylpolypyrrolidone and polymeric amberlites (XAD7HP, XAD16) are commonly used for the adsorptive downstream processing of polyphenols from renewable resources. In this study, beta-zeolite-based adsorbent systems were examined, and their properties were compared to organic resins. Batch adsorption experiments were conducted with synthetic solutions of major polyphenols. Adsorption isotherms and desorption characteristics of individual adsorbent were determined based on these results. Maximum adsorption capacities were calculated using the Langmuir model. For example, the zeolites had capacities up to 203.2 mg/g for ferulic acid. To extend these results to a complex system, additional experiments were performed on rapeseed meal and wheat seed extracts as representative renewable resources. HPLC analysis showed that with 7.5% w/v, which is regarded as the optimum amount of zeolites, zeolites A and B could bind 100% of the major polyphenols as well as release polyphenols at high yields. Additionally, regeneration experiments were performed with isopropyl alcohol at 99°C to evaluate how zeolites regenerate under mild conditions. The results showed only a negligible loss of adsorption capacity and no loss of desorption capacity. In summary, it was concluded that beta-zeolites were promising adsorbents for developing new processes to isolate polyphenols from renewable resources. Y1 - 2013 U6 - http://dx.doi.org/10.1002/elsc.201200188 VL - 13 IS - 3 SP - 239 EP - 246 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Al-Kaidy, Huschyar A1 - Wollny, Steffen A1 - Ulber, Roland T1 - Functionalized magnetizable particles for downstream processing in single-use systems JF - Chemie Ingenieur Technik N2 - Biotechnological downstream processing is usually an elaborate procedure, requiring a multitude of unit operations to isolate the target component. Besides the disadvantageous space-time yield, the risks of cross-contaminations and product loss grow fast with the complexity of the isolation procedure. A significant reduction of unit operations can be achieved by application of magnetic particles, especially if these are functionalized with affinity ligands. As magnetic susceptible materials are highly uncommon in biotechnological processes, target binding and selective separation of such particles from fermentation or reactions broths can be done in a single step. Since the magnetizable particles can be produced from iron salts and low priced polymers, a single-use implementation of these systems is highly conceivable. In this article, the principles of magnetizable particles, their synthesis and functionalization are explained. Furthermore, applications in the area of reaction engineering, microfluidics and downstream processing are discussed focusing on established single-use technologies and development potential. Y1 - 2013 U6 - http://dx.doi.org/10.1002/cite.201200130 VL - 85 IS - 1-2: Special Issue: Single-Use Technology SP - 76 EP - 86 PB - Wiley CY - Weinheim ER - TY - PAT A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - A system and a method for the implementation of chemical, biological or physical reactions [Europäische Patentanmeldung] N2 - The invention relates to a system for the implementation of chemical, biological or physical reactions, consisting of - one or more magnetic micro-reactors, each comprising a shell made of hydrophobic magnetic nanoparticles encapsulating an aqueous core, - a plane platform comprising a surface to receive the micro-reactors, - a source that generates a magnetic field above or underneath the platform for manipulating the one or more hydrophobic magnetic micro-reactors, or for moving them along the surface of the platform from one position to another position, characterized in that the aqueous core of the one or more magnetic micro-reactors contains a reaction solution or buffer, and wherein the magnetic field generated by the source correlates to a defined position on the surface of the platform. Y1 - 2013 PB - Europäisches Patentamt CY - Den Hague ER - TY - PAT A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - A method for production of single-stranded nucleic acids [Europäische Patentanmeldung] Y1 - 2013 PB - Europäisches Patentamt CY - Den Hague ER - TY - JOUR A1 - Pellegrini, Paul A. A1 - Howell, Nicholas R. A1 - Shepherd, Rachael K. A1 - Lengkeek, Nigel A. A1 - Paulßen, Elisabeth A1 - Katsifis, Andrew G. A1 - Greguric, Ivan T1 - Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells JF - Molecules Y1 - 2013 U6 - http://dx.doi.org/10.3390/molecules18067160 SN - 1420-3049 VL - 18 IS - 6 SP - 7160 EP - 7178 PB - MDPI CY - Basel ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Le, Van So A1 - Lengkeek, Nigel A1 - Pellegrini, Paul A1 - Jackson, Tim A1 - Greguric, Ivan A1 - Weiner, Ron T1 - Influence of Metal Ions on the 68Ga-labeling of DOTATATE JF - Applied Radiation and Isotopes Y1 - 2013 U6 - http://dx.doi.org/10.1016/j.apradiso.2013.08.010 SN - 1872-9800 VL - 82 SP - 232 EP - 238 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Xenobiotic receptor humanized mice and their utility JF - Drug Metabolism Reviews Y1 - 2013 U6 - http://dx.doi.org/10.3109/03602532.2012.738687 SN - 1097-9883 IS - 1 SP - 110 EP - 121 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Huck, Christina A1 - Schiffels, Johannes A1 - Herrera, Cony N. A1 - Schelden, Maximilian A1 - Selmer, Thorsten A1 - Poghossian, Arshak A1 - Baumann, Marcus A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Metabolic responses of Escherichia coli upon glucose pulses captured by a capacitive field-effect sensor JF - Physica Status Solidi (A) N2 - Living cells are complex biological systems transforming metabolites taken up from the surrounding medium. Monitoring the responses of such cells to certain substrate concentrations is a challenging task and offers possibilities to gain insight into the vitality of a community influenced by the growth environment. Cell-based sensors represent a promising platform for monitoring the metabolic activity and thus, the “welfare” of relevant organisms. In the present study, metabolic responses of the model bacterium Escherichia coli in suspension, layered onto a capacitive field-effect structure, were examined to pulses of glucose in the concentration range between 0.05 and 2 mM. It was found that acidification of the surrounding medium takes place immediately after glucose addition and follows Michaelis–Menten kinetic behavior as a function of the glucose concentration. In future, the presented setup can, therefore, be used to study substrate specificities on the enzymatic level and may as well be used to perform investigations of more complex metabolic responses. Conclusions and perspectives highlighting this system are discussed. Y1 - 2013 U6 - http://dx.doi.org/10.1002/pssa.201200900 SN - 0031-8965 VL - 210 IS - 5 SP - 926 EP - 931 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Bäcker, Matthias A1 - Rakowski, D. A1 - Poghossian, Arshak A1 - Biselli, Manfred A1 - Wagner, Patrick A1 - Schöning, Michael Josef T1 - Chip-based amperometric enzyme sensor system for monitoring of bioprocesses by flow-injection analysis JF - Journal of Biotechnology N2 - A microfluidic chip integrating amperometric enzyme sensors for the detection of glucose, glutamate and glutamine in cell-culture fermentation processes has been developed. The enzymes glucose oxidase, glutamate oxidase and glutaminase were immobilized by means of cross-linking with glutaraldehyde on platinum thin-film electrodes integrated within a microfluidic channel. The biosensor chip was coupled to a flow-injection analysis system for electrochemical characterization of the sensors. The sensors have been characterized in terms of sensitivity, linear working range and detection limit. The sensitivity evaluated from the respective peak areas was 1.47, 3.68 and 0.28 μAs/mM for the glucose, glutamate and glutamine sensor, respectively. The calibration curves were linear up to a concentration of 20 mM glucose and glutamine and up to 10 mM for glutamate. The lower detection limit amounted to be 0.05 mM for the glucose and glutamate sensor, respectively, and 0.1 mM for the glutamine sensor. Experiments in cell-culture medium have demonstrated a good correlation between the glutamate, glutamine and glucose concentrations measured with the chip-based biosensors in a differential-mode and the commercially available instrumentation. The obtained results demonstrate the feasibility of the realized microfluidic biosensor chip for monitoring of bioprocesses. Y1 - 2013 U6 - http://dx.doi.org/10.1016/j.jbiotec.2012.03.014 SN - 0168-1656 VL - 163 IS - 4 SP - 371 EP - 376 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Winckler, Silvia A1 - Krueger, Rolf A1 - Schnitzler, Thomas A1 - Zang, Werner A1 - Fischer, Rainer A1 - Biselli, Manfred T1 - A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach JF - Bioprocess and biosystems engineering N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1007/s00449-013-1062-8 SN - 1615-7591 (Print) 1615-7605 (Online) VL - 37 IS - 5 SP - 901 EP - 912 PB - Springer CY - Berlin, Heidelberg ER - TY - JOUR A1 - Heinze, Daniel A1 - Mang, Thomas A1 - Peter, Karin A1 - Möller, Martin A1 - Weichold, Oliver T1 - Synthesis of low molecular weight poly(vinyl acetate) and its application as plasticizer JF - Journal of applied polymer science N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40226 SN - 1097-4628 (E-Journal); 0021-8995 (Print) VL - 131 IS - 9 SP - Article No. 40226 PB - Wiley CY - New York ER - TY - JOUR A1 - Wang, Ren-Qi A1 - Druckenmüller, Katharina A1 - Elbers, Gereon A1 - Guenther, Klaus A1 - Croué, Jean-Philippe T1 - Analysis of aquatic-phase natural organic matter by optimized LDI-MS method JF - Journal of mass spectrometry N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/jms.3321 SN - 1096-9888 VL - 49 IS - 2 SP - 154 EP - 160 PB - Wiley CY - Bognor Regis ER - TY - JOUR A1 - Heine, A. A1 - Herrmann, G. A1 - Selmer, Thorsten A1 - Terwesten, F. A1 - Buckel, W. A1 - Reuter, K. T1 - High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily JF - Proteins N2 - 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 Å as well as in complex with CoA at a resolution of 1.59 Å. 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/prot.24557 SN - 1097-0134 (E-Journal); 0887-3585 (Print) VL - 82 IS - 9 SP - 2041 EP - 2053 PB - Wiley-Liss CY - New York ER - TY - JOUR A1 - Takenaga, Shoko A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Öhlschläger, Peter A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis–Menten-like kinetics for cell culturing JF - Physica status solidi A : Applications and materials science N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330464 SN - 1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print) VL - 211 IS - 6 SP - 1410 EP - 1415 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Whitehead, Mark A1 - Öhlschläger, Peter A1 - Almajhdi, Fahad N. A1 - Alloza, Leonor A1 - Marzábal, Pablo A1 - Meyers, Ann E. A1 - Hitzeroth, Inga I. A1 - Rybicki, Edward P. T1 - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice JF - BMC cancer Y1 - 2014 U6 - http://dx.doi.org/10.1186/1471-2407-14-367 SN - 1471-2407 IS - 14:367 SP - 1 EP - 15 PB - BioMed Central CY - London ER - TY - JOUR A1 - Küppers, Tobias A1 - Steffen, Victoria A1 - Hellmuth, Hendrik A1 - O'Connell, Timothy A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Wiechert, Wolfgang T1 - Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer JF - Microbial cell factories Y1 - 2014 U6 - http://dx.doi.org/10.1186/1475-2859-13-46 SN - 1475-2859 (E-Journal) VL - 13 SP - Article No. 46 PB - BioMed Central CY - London ER - TY - JOUR A1 - Guo, Yuanyuan A1 - Miyamoto, Ko-ichiro A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Theoretical study and simulation of light-addressable potentiometric sensors JF - Physica status solidi (A) : applications and materials N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/pssa.201330354 SN - 0031-8965 VL - 211 IS - 6 SP - 1467 EP - 1472 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Ratke, Lorenz A1 - Milow, Barbara A1 - Lisinski, Susanne A1 - Hoepfner, Sandra T1 - On an effect of fine ceramic particles on the structure of aerogels JF - Microgravity science and technology Y1 - 2014 U6 - http://dx.doi.org/10.1007/s12217-014-9380-2 SN - 0938-0108 ; 1875-0494 VL - 26 SP - 103 EP - 110 PB - Springer Nature CY - Heidelberg ER - TY - JOUR A1 - Handtke, Stefan A1 - Volland, Sonja A1 - Methling, Karen A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Nehls, Jenny A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Liesegang, Heiko A1 - Voigt, Birgit A1 - Daniel, Rolf A1 - Hecker, Michael T1 - Cell physiology of the biotechnological relevant bacterium Bacillus pumilus - An omics-based approach JF - Journal of Biotechnology N2 - Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC–MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.jbiotec.2014.08.028 SN - 1873-4863 (E-Journal); 0168-1656 (Print) IS - 192(A) SP - 204 EP - 214 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Nachtrodt, Frederik A1 - Tietsch, Wolfgang A1 - Mostacci, Domiziano A1 - Scherer, Ulrich W. T1 - Set-up and first operation of a plasma oven for treatment of low level radioactive wastes JF - Nuclear technology and radiation protection Y1 - 2014 U6 - http://dx.doi.org/10.2298/NTRP140SS47N SN - 1451-3994 VL - 29 IS - Suppl. SP - 47 EP - 51 PB - VINČA Institute of Nuclear Sciences CY - Belgrad ER - TY - JOUR A1 - Raue, Markus A1 - Wambach, M. A1 - Glöggler, S. A1 - Grefen, Dana A1 - Kaufmann, R. A1 - Abetz, C. A1 - Georgopanos, P. A1 - Handge, U. A. A1 - Mang, Thomas A1 - Blümich, B. A1 - Abetz, V. T1 - Investigation of historical hard rubber ornaments of Charles Goodyear JF - Macromolecular chemistry and physics Y1 - 2014 SN - 1022-1352 VL - Vol. 215 IS - No. 3 SP - 245 EP - 254 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pasteur, Aline A1 - Tippkötter, Nils A1 - Kampeis, Percy A1 - Ulber, Roland T1 - Optimization of high gradient magnetic separation filter units for the purification of fermentation products JF - IEEE TRANSACTIONS ON MAGNETICS N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1109/TMAG.2014.2325535 SN - 0018-9464 N1 - Article Sequence Number: 5000607 INSPEC Accession Number: 14663042 VL - 50 IS - 10 SP - Artikel 5000607 PB - IEEE CY - New York, NY ER - TY - JOUR A1 - Tippkötter, Nils A1 - Wollny, Steffen A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - 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 JF - Engineering in Life Sciences N2 - 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. Y1 - 2014 U6 - http://dx.doi.org/10.1002/elsc.201300113 SN - 1618-2863 VL - 14 IS - 4 SP - 425 EP - 432 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Tippkötter, Nils A1 - Duwe, Anna-Maria A1 - Wiesen, Sebastian A1 - Sieker, Tim A1 - Ulber, Roland T1 - Enzymatic hydrolysis of beech wood lignocellulose at high solid contents and its utilization as substrate for the production of biobutanol and dicarboxylic acids JF - Bioresource Technology N2 - The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9%, 17% and 23% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.biortech.2014.06.052 VL - 167 SP - 447 EP - 455 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hoehr, Cornelia A1 - Paulßen, Elisabeth A1 - Benard, Francois A1 - Lee, Chris Jaeil A1 - Hou, Xinchi A1 - Badesso, Brian A1 - Ferguson, Simon A1 - Miao, Qing A1 - Yang, Hua A1 - Buckley, Ken A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Ruth, Thomas A1 - Celler, Anna A1 - Schaffer, Paul T1 - ⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron JF - Nuclear medicine and biology N2 - Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations. Y1 - 2014 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2013.12.016 SN - 1872-9614 VL - 41 IS - 5 SP - 401 EP - 406 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Al-Kaidy, H. A1 - Ulber, R. A1 - Tippkötter, Nils T1 - A platform technology for the automated reaction control in magnetizable micro-fluidic droplets T2 - Biomaterials - made in bioreactors : book of abstracts, May 26 - 28, 2014, Radisson Blu Park Hotel and Conference Dentre, Radebeul, Germany Y1 - 2014 SP - 21 EP - 22 PB - DECHEMA CY - Frankfurt am Main ER - TY - JOUR A1 - Luisier, Raphaëlle A1 - Lempiäinen, Harri A1 - Scherbichler, Nina A1 - Braeuning, Albert A1 - Geissler, Miriam A1 - Dubost, Valerie A1 - Müller, Arne A1 - Scheer, Nico A1 - Chibout, Salah-Dine A1 - Hara, Hisanori A1 - Picard, Frank A1 - Theil, Diethilde A1 - Couttet, Philippe A1 - Vitobello, Antonio A1 - Grenet, Olivier A1 - Grasl-Kraupp, Bettina A1 - Ellinger-Ziegelbauer, Heidrung A1 - Thomson, John P. A1 - Meehan, Richard R. A1 - Elcombe, Clifford R. A1 - Henderson, Colin J. A1 - Wolf, C. Roland A1 - Schwarz, Michael A1 - Moulin, Pierre A1 - Terranova, Remi A1 - Moggs, Jonathan G. T1 - Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors JF - Toxicological Sciences N2 - The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB. Y1 - 2014 U6 - http://dx.doi.org/https://doi.org/10.1093/toxsci/kfu038 SN - 1094-2025 VL - 139 IS - 2 SP - 501 EP - 511 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Salpati, Laurent A1 - Chu, Xiaoyan A1 - Chen, Liangfu A1 - Prasad, Bhagwat A1 - Dallas, Shannon A1 - Evers, Raymond A1 - Mamaril-Fishman, Donna A1 - Geier, Ethan G. A1 - Kehler, Jonathan A1 - Kunta, Jeevan A1 - Mezler, Mario A1 - Laplanche, Loic A1 - Pang, Jodie A1 - Soars, Matthew G. A1 - Unadkat, Jashvant D. A1 - van Waterschoot, Robert A.B. A1 - Yabut, Jocelyn A1 - Schinkel, Alfred H. A1 - Scheer, Nico A1 - Rode, Anja T1 - Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins JF - Drug Metabolism and Disposition N2 - Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography–tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057976 SN - 1521-009X VL - 42 IS - 8 SP - 1301 EP - 1313 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Mclaughlin, Lesley A. A1 - Rode, Anja A1 - MacLeod, Alastair Kenneth A1 - Henderson, Colin J. A1 - Wolf, Roland C. T1 - Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism JF - Drug Metabolism and Disposition N2 - In humans, 75% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15%) and larger livers (20%). Changes in hepatic morphology and a decreased blood glucose (30%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity. Y1 - 2014 U6 - http://dx.doi.org/10.1124/dmd.114.057885 SN - 1521-009X VL - 42 IS - 6 SP - 1022 EP - 1030 PB - ASPET CY - Bethesda, Md. ER - TY - JOUR A1 - Scheer, Nico A1 - Wolf, C. Roland T1 - Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications JF - Xenobiotica N2 - 1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug–drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug–drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed. KW - transporters KW - human metabolites KW - drug metabolising enzymes KW - drug–drug interactions KW - bioavailability Y1 - 2014 U6 - http://dx.doi.org/10.3109/00498254.2013.815831 SN - 1366-5928 VL - 44 IS - 2 SP - 96 EP - 108 PB - Taylor & Francis CY - Abingdon ER - TY - JOUR A1 - Hentschke, Reinhard A1 - Hager, Jonathan A1 - Hojdis, Nils T1 - Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers JF - Journal of Applied Polymer Science N2 - Recently, we have suggested a nanomechanical model for dissipative loss in filled elastomer networks in the context of the Payne effect. The mechanism is based on a total interfiller particle force exhibiting an intermittent loop, due to the combination of short-range repulsion and dispersion forces with a long-range elastic attraction. The sum of these forces leads, under external strain, to a spontaneous instability of “bonds” between the aggregates in a filler network and attendant energy dissipation. Here, we use molecular dynamics simulations to obtain chemically realistic forces between surface modified silica particles. The latter are combined with the above model to estimate the loss modulus and the low strain storage modulus in elastomers containing the aforementioned filler-compatibilizer systems. The model is compared to experimental dynamic moduli of silica filled rubbers. We find good agreement between the model predictions and the experiments as function of the compatibilizer's molecular structure and its bulk concentration. KW - theory and modeling KW - supramolecular structures KW - rubber KW - mechanical properties KW - elastomers Y1 - 2014 U6 - http://dx.doi.org/10.1002/app.40806 SN - 1097-4628 VL - 131 IS - 18 SP - 1 EP - 9 PB - Wiley CY - New York, NY ER - TY - JOUR A1 - Schroeter, Rebecca A1 - Hoffmann, Tamara A1 - Voigt, Birgit A1 - Meyer, Hanna A1 - Bleisteiner, Monika A1 - Muntel, Jan A1 - Jürgen, Britta A1 - Albrecht, Dirk A1 - Becher, Dörte A1 - Lalk, Michael A1 - Evers, Stefan A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Putzer, Harald A1 - Hecker, Michael A1 - Schweder, Thomas A1 - Bremer, Erhard T1 - Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges JF - PLoS ONE N2 - The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0080956 SN - 1932-6203 VL - 8 IS - 11 PB - PLOS CY - San Francisco ER - TY - JOUR A1 - Handtke, Stefan A1 - Schroeter, Rebecca A1 - Jürgen, Britta A1 - Methling, Karen A1 - Schlüter, Rabea A1 - Albrecht, Dirk A1 - Hijum, Sacha A. F. T. van A1 - Bongaerts, Johannes A1 - Maurer, Karl-Heinz A1 - Lalk, Michael A1 - Schweder, Thomas A1 - Hecker, Michael A1 - Voigt, Birgit T1 - Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress JF - PLOS one N2 - Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus. Y1 - 2014 U6 - http://dx.doi.org/10.1371/journal.pone.0085625 SN - 1932-6203 VL - 9 IS - 1 PB - PLOS CY - San Francisco ER - TY - CHAP A1 - Frotscher, Ralf A1 - Goßmann, Matthias A1 - Raatschen, Hans-Jürgen A1 - Temiz Artmann, Aysegül A1 - Staat, Manfred T1 - Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM T2 - Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45) N2 - We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments. Y1 - 2015 SN - 978-3-319-02534-6 ; 978-3-319-02535-3 SP - 187 EP - 212 PB - Springer CY - Heidelberg ER - TY - JOUR A1 - Seifarth, Volker A1 - Goßmann, Matthias A1 - Grosse, J. O. A1 - Becker, C. A1 - Heschel, I. A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds JF - Urologia Internationalis Y1 - 2015 U6 - http://dx.doi.org/10.1159/000368419 SN - 0042-1138 VL - 2015 IS - 95 SP - 106 EP - 113 PB - Karger CY - Basel ER - TY - JOUR A1 - Pilas, Johanna A1 - Iken, Heiko A1 - Selmer, Thorsten A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Development of a multi‐parameter sensor chip for the simultaneous detection of organic compounds in biogas processes JF - Physica status solidi (a) N2 - An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431894 SN - 1862-6319 VL - 212 IS - 6 SP - 1306 EP - 1312 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Kirschbaum, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide JF - Physica status solidi (a) N2 - Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201431944 SN - 1862-6319 VL - 212 IS - 6 SP - 1368 EP - 1374 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Schiffels, Johannes A1 - Selmer, Thorsten T1 - A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro JF - Biotechnology and Bioengineering Y1 - 2015 U6 - http://dx.doi.org/10.1002/bit.25658 SN - 1097-0290 VL - 112 IS - 11 SP - 2360 EP - 2372 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Voigt, Birgit A1 - Albrecht, Dirk A1 - Sievers, Susanne A1 - Becher, Dörte A1 - Bongaerts, Johannes A1 - Evers, Stefan A1 - Schweder, Thomas A1 - Maurer, Karl-Heinz A1 - Hecker, Michael T1 - High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium JF - Proteomics Y1 - 2015 U6 - http://dx.doi.org/10.1002/pmic.201400504 SN - 1615-9861 VL - 15 IS - 15 SP - 2629 EP - 2633 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Molinnus, Denise A1 - Bäcker, Matthias A1 - Siegert, Petra A1 - Willenberg, H. A1 - Poghossian, Arshak A1 - Keusgen, M. A1 - Schöning, Michael Josef T1 - Detection of Adrenaline Based on Substrate Recycling Amplification JF - Procedia Engineering N2 - An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions has been studied. Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.proeng.2015.08.708 SN - 1877-7058 N1 - Eurosensors 2015 VL - 120 SP - 540 EP - 543 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Pilas, Johanna A1 - Mariano, K. A1 - Keusgen, M. A1 - Selmer, Thorsten A1 - Schöning, Michael Josef T1 - Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes JF - Procedia Engineering Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.proeng.2015.08.702 SN - 1877-7058 N1 - Part of special issue "Eurosensors 2015" VL - 120 SP - 532 EP - 535 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Takenaga, Shoko A1 - Schneider, Benno A1 - Erbay, E. A1 - Biselli, Manfred A1 - Schnitzler, Thomas A1 - Schöning, Michael Josef A1 - Wagner, Torsten T1 - Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process JF - Physica status solidi (a) N2 - A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation. Y1 - 2015 U6 - http://dx.doi.org/10.1002/pssa.201532053 SN - 1862-6319 VL - 212 IS - 6 SP - 1347 EP - 1352 PB - Wiley CY - Weinheim ER - TY - CHAP A1 - Srivastava, Alok A1 - Knolle, Friedhart A1 - Hoyler, Friedrich A1 - Scherer, Ulrich W. A1 - Schnug, Ewald T1 - Uranium Toxicity in the State of Punjab in North-Western India T2 - Management of Natural Resources in a Changing Environment N2 - Lately there has been an increasing concern about uranium toxicity in some districts of Punjab State located in the North Western part of India after the publication of a report (Blaurock-Busch et al. 2010) which showed that the concentration of uranium in hair and urine of children suffering from physical deformities, neurological and mental disorder from Malwa region (Fig. 1) of Punjab State was manifold higher than the reference ranges. A train which connects the affected region with the nearby city of Bikaner which has a Cancer Hospital has been nicknamed as Cancer Express due to the frenzy generated on account of uranium related toxicity. Y1 - 2015 SN - 978-3-319-12559-6 U6 - http://dx.doi.org/10.1007/978-3-319-12559-6_21 SP - 271 EP - 275 PB - Springer CY - Cham ER - TY - JOUR A1 - Cehreli, Ruksan A1 - Akpinar, Hale A1 - Temiz Artmann, Aysegül A1 - Sagol, Ozgul T1 - Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis JF - Gastroenterology Research Y1 - 2015 U6 - http://dx.doi.org/10.14740/gr683w SN - 1918-2813 VL - 8 IS - 5 SP - 265 EP - 273 ER - TY - CHAP A1 - Breuer, Lars A1 - Raue, Markus A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, Ronald A1 - Wagner, Torsten T1 - Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications T2 - 12. Dresdner Sensor-Symposium 2015 Y1 - 2015 U6 - http://dx.doi.org/10.5162/12dss2015/P5.8 SP - 206 EP - 209 ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Duwe, Anna A1 - Huster, Manuel A1 - Muffler, Kai A1 - Schlegel, Christin A1 - Tim, Sieker A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Biotechnology and bioprocess engineering – from the first ullmann's article to recent trends JF - ChemBioEng Reviews N2 - For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed. Y1 - 2015 U6 - http://dx.doi.org/10.1002/cben.201500008 VL - 2 IS - 3 SP - 175 EP - 184 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Thiel, Alexander A1 - Muffler, Kai A1 - Tippkötter, Nils A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Hruschka, Steffen M. A1 - Ulber, Roland T1 - A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal JF - Journal of Chemical Technology and Biotechnology N2 - BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2% and 40.1%, respectively. The steps were then combined in two different ways: (a) a ‘sequential process’ using the zeolite and A200 in batch processes; and (b) a ‘parallel process’ using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry Y1 - 2015 U6 - http://dx.doi.org/10.1002/jctb.4664 VL - 90 IS - 11 SP - 1999 EP - 2006 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Wiesen, Sebastian A1 - Tippkötter, Nils A1 - Muffler, Kai A1 - Suck, Kirstin A1 - Sohling, Ulrich A1 - Ruf, Friedrich A1 - Ulber, Roland T1 - Adsorption of fatty acids to layered double hydroxides in aqueous systems JF - Adsorption N2 - Due to their anion exchange characteristics, layered double hydroxides (LDHs) are suitable for the detoxification of aqueous, fatty acid containing fermentation substrates. The aim of this study is to examine the adsorption mechanism, using crude glycerol from plant oil esterification as a model system. Changes in the intercalation structure in relation to the amount of fatty acids adsorbed are monitored by X-ray diffraction and infra-red spectroscopy. Additionally, calcination of LDH is investigated in order to increase the binding capacity for fatty acids. Our data propose that, at ambient temperature, fatty acids can be bound to the hydrotalcite by adsorption or in addition by intercalation, depending on fatty acid concentration. The adsorption of fatty acids from crude glycerol shows a BET-like behavior. Above a fatty acid concentration of 3.5 g L−1, intercalation of fatty acids can be shown by the appearance of an increased interlayer spacing. This observation suggests a two phase adsorption process. Calcination of LDHs allows increasing the binding capacity for fatty acids by more than six times, mainly by reduction of structural CO32−. Y1 - 2015 VL - 21 IS - 6-7 SP - 459 EP - 466 PB - Springer CY - Berlin ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Hoehr, Cornelia A1 - Hou, Xinchi A1 - Hanemaayer, Victoire A1 - Zeisler, Stefan A1 - Adam, Michael J. A1 - Ruth, Thomas J. A1 - Celler, Anna A1 - Buckley, Ken A1 - Benard, Francois A1 - Schaffer, Paul T1 - Production of Y-86 and other radiometals for research purposes using a solution target system JF - Nuclear medicine and biology Y1 - 2015 U6 - http://dx.doi.org/10.1016/j.nucmedbio.2015.06.005 SN - 1872-9614 VL - 42 IS - 11 SP - 842 EP - 849 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Scheer, Nico A1 - Kapelyukh, Yury A1 - Rode, Anja A1 - Oswald, Stefan A1 - Busch, Diana A1 - Mclaughlin, Lesley A. A1 - Lin, De A1 - Henderson, Colin J. A1 - Wolf, C. Roland T1 - Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065656 SN - 1521-009x VL - 43 IS - 11 SP - 1679 EP - 1690 PB - ASPET CY - Bethesda ER - TY - JOUR A1 - Hough, Lindsay B. A1 - Nalwalk, Julia W. A1 - Ding, Xinxin A1 - Scheer, Nico T1 - Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms JF - Drug Metabolism and Disposition Y1 - 2015 U6 - http://dx.doi.org/10.1124/dmd.115.065490 SN - 1521-009x VL - 43 IS - 9 SP - 1326 EP - 1330 ER - TY - JOUR A1 - Henderson, Colin J. A1 - Mclaughlin, Lesley A. A1 - Scheer, Nico A1 - Stanley, Lesley A. A1 - Wolf, C. Roland T1 - Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s JF - Molecular Pharmacology Y1 - 2015 U6 - http://dx.doi.org/10.1124/mol.114.097394 SN - 1521-0111 VL - 87 IS - 4 SP - 733 EP - 739 PB - ASPET CY - Bethesda ER - TY - CHAP A1 - Wolf, C. Roland A1 - Kapelyukh, Yury A1 - Scheer, Nico A1 - Henderson, Colin J. ED - Wilson, Alan G. E. T1 - Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs N2 - The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic. Y1 - 2015 SN - 978-1-78262-778-4 U6 - http://dx.doi.org/10.1039/9781782622376-00152 SP - 152 EP - 176 PB - RSC Publ. CY - Cambridge ER - TY - JOUR A1 - Hager, Jonathan A1 - Hentschke, Reinhard A1 - Hojdis, Nils A1 - Karimi-Varzaneh, Hossein Ali T1 - Computer Simulation of Particle–Particle Interaction in a Model Polymer Nanocomposite JF - Macromolecules Y1 - 2015 U6 - http://dx.doi.org/10.1021/acs.macromol.5b01864 SN - 1520-5835 VL - 48 IS - 24 SP - 9039 EP - 9049 ER - TY - PAT A1 - Stadtmüller, Ralf A1 - Tippkötter, Nils A1 - Ulber, Roland T1 - Method for production of single-stranded macronucleotides N2 - The invention relates to a method for production of single-stranded macronucleotides by amplifying and ligating an extended monomeric single-stranded target nucleic acid sequence (targetss) into a repetitive cluster of double-stranded target nucleic acid sequences (targetds), and subsequently cloning the construct into a vector (aptagene vector). The aptagene vector is transformed into host cells for replication of the aptagene and isolated in order to optain single-stranded target sequences (targetss). The invention also relates to single-stranded nucleic acids, produced by a method of the invention. Y1 - 2015 N1 - Patent auch unter EP2774996, EP2774996, US2017145460 und US9944966 veröffentlicht. ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Strobel, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems JF - Physica status solidi (a) N2 - Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium. Y1 - 2016 U6 - http://dx.doi.org/10.1002/pssa.201533056 SN - 1862-6300 VL - 213 IS - 6 SP - 1520 EP - 1525 PB - Wiley-VCH CY - Weinheim ER - TY - CHAP A1 - Kasper, Katharina A1 - Schiffels, Johannes A1 - Krafft, Simone A1 - Kuperjans, Isabel A1 - Elbers, Gereon A1 - Selmer, Thorsten T1 - Biogas Production on Demand Regulated by Butyric Acid Addition T2 - IOP Conference Series: Earth and Environmental Science. Bd. 32 Y1 - 2016 U6 - http://dx.doi.org/10.1088/1755-1315/32/1/012009 SN - 1755-1315 N1 - ICARET 2016, International Conference on Advances in Renewable Energy and Technologies, Putrajaya, MY, Feb 23-25, 2016 VL - 32 SP - 012009/1 EP - 012009/4 ER - TY - JOUR A1 - Niedermeyer, Angela A1 - Zhou, Bei A1 - Dursun, Gözde A1 - Temiz Artmann, Aysegül A1 - Markert, Bernd T1 - An examination of tissue engineered scaffolds in a bioreactor JF - Proceedings in Applied Mathematics and Mechanics PAMM N2 - Replacement tissues, designed to fill in articular cartilage defects, should exhibit the same properties as the native material. The aim of this study is to foster the understanding of, firstly, the mechanical behavior of the material itself and, secondly, the influence of cultivation parameters on cell seeded implants as well as on cell migration into acellular implants. In this study, acellular cartilage replacement material is theoretically, numerically and experimentally investigated regarding its viscoelastic properties, where a phenomenological model for practical applications is developed. Furthermore, remodeling and cell migration are investigated. Y1 - 2016 U6 - http://dx.doi.org/10.1002/pamm.201610038 SN - 1617-7061 N1 - Joint Annual Meeting of DMV and GAMM 2016, 87th Annual Meeting of the International Association of Applied Mathematics and Mechanics (GAMM) and Deutsche Mathematiker-Vereinigung (DMV), Braunschweig, DE, Mar 7-11, 2016 VL - 16 IS - 1 SP - 99 EP - 100 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Heinze, D. A1 - Mang, Thomas A1 - Popescu, C. A1 - Weichold, O. T1 - Effect of side chain length and degree of polymerization on the decomposition and crystallization behaviour of chlorinated poly(vinyl ester) oligomers JF - Thermochimica Acta N2 - Four members of a homologous series of chlorinated poly(vinyl ester) oligomers CCl₃–(CH₂CH (OCO(CH₂)ₘCH₃))ₙ–Cl with degrees of polymerization of 10 and 20 were prepared by telomerisation using carbon tetrachloride. The number of side chain carbon atoms ranges from 2 (poly(vinyl acetate) to 18 (poly(vinyl stearate)). The effect of the n-alkyl side chain length and of the degree of polymerization on the thermal stability and crystallization behaviour of the synthesized compounds was investigated. All oligomers degrade in two major steps by first losing HCl and side chains with subsequent breakdown of the backbone. The members with short side chains, up to poly(vinyl octanoate), are amorphous and show internal plasticization, whereas those with high number of side chain carbon atoms are semi-crystalline due to side-chain crystallization. A better packing for poly(vinyl stearate) is also noticeable. The glass transition and melting temperatures as well as the onset temperature of decomposition are influenced to a larger extent by the side chain length than by the degree of polymerization. Thermal stability is improved if both the size and number of side chains increase, but only a long side chain causes a significant increase of the resistance to degradation. This results in a stabilization of PVAc so that oligomers from poly(vinyl octanoate) on are stable under atmospheric conditions. Thus, the way to design stable, chlorinated PVEs oligomers is to use a long n-alkyl side chain. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.tca.2016.05.015 SN - 0040-6031 (electronic) VL - 637 SP - 143 EP - 153 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Molinnus, Denise A1 - Sorich, Maren A1 - Bartz, Alexander A1 - Siegert, Petra A1 - Willenberg, Holger S. A1 - Lisdat, Fred A1 - Poghossian, Arshak A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate JF - Sensors and Actuators B: Chemical N2 - An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer’s solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.snb.2016.06.064 SN - 0925-4005 VL - 237 SP - 190 EP - 195 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Ghosch, S. A1 - Baier, M. A1 - Schütz, J. A1 - Schneider, Felix A1 - Scherer, Ulrich W. T1 - Analysis of electronic autoradiographs by mathematical post-processing JF - Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology N2 - Autoradiography is a well-established method of nuclear imaging. When different radionuclides are present simultaneously, additional processing is needed to distinguish distributions of radionuclides. In this work, a method is presented where aluminium absorbers of different thickness are used to produce images with different cut-off energies. By subtracting images pixel-by-pixel one can generate images representing certain ranges of β-particle energies. The method is applied to the measurement of irradiated reactor graphite samples containing several radionuclides to determine the spatial distribution of these radionuclides within pre-defined energy windows. The process was repeated under fixed parameters after thermal treatment of the samples. The greyscale images of the distribution after treatment were subtracted from the corresponding pre-treatment images. Significant changes in the intensity and distribution of radionuclides could be observed in some samples. Due to the thermal treatment parameters the most significant differences were observed in the ³H and ¹⁴C inventory and distribution. Y1 - 2016 U6 - http://dx.doi.org/10.1080/10420150.2016.1155587 SN - 1029-4953 VL - 171 IS - 1-2 SP - 161 EP - 172 PB - Taylor & Francis CY - London ER - TY - JOUR A1 - Rösch, C. A1 - Kratz, F. A1 - Hering, T. A1 - Trautmann, S. A1 - Umanskaya, N. A1 - Tippkötter, Nils A1 - Müller-Renno, C.M. A1 - Ulber, R. A1 - Hannig, M. A1 - Ziegler, C. T1 - Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity JF - Colloids and Surfaces B: Biointerfaces N2 - The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.colsurfb.2016.09.048 VL - 149 IS - 1 SP - 115 EP - 121 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Roth, Jasmine A1 - Tippkötter, Nils T1 - Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium JF - Cellulose Chemistry and Technology N2 - Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹. Y1 - 2016 VL - 50 IS - 3-4 SP - 405 EP - 410 PB - Editura Academiei Romane CY - Bukarest ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Tippkötter, Nils T1 - Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase JF - Engineering in Life Sciences N2 - In the field of biotechnology and molecular biology, the use of small liquid volumes has significant advantages. In particular, screening and optimization runs with acceptable amounts of expensive and hardly available catalysts, reagents, or biomolecules are feasible with microfluidic technologies. The presented new microfluidic system is based on the inclusion of small liquid volumes by a protective shell of magnetizable microparticles. Hereby, discrete aqueous microreactor drops with volumes of 1–30 μL can be formed on a simple planar surface. A digital movement and manipulation of the microreactor is performed by overlapping magnetic forces. The magnetic forces are generated by an electrical coil matrix positioned below a glass plate. With the new platform technology, several discrete reaction compartments can be moved simultaneously on one surface. Due to the magnetic fields, the reactors can even be merged to initiate reactions by mixing or positioned above surface-immobilized catalysts and then opened by magnetic force. Comparative synthesis routes of the magnetizable shell particles and superhydrophobic glass slides including their performance and stability with the reaction platform are described. The influence of diffusive mass transport during the catalyzed reaction is discussed by evaluation finite element model of the microreactor. Furthermore, a first model dye reaction of the enzyme laccase has been established. Y1 - 2016 U6 - http://dx.doi.org/10.1002/elsc.201400124 VL - 16 IS - 3 SP - 222 EP - 230 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Al-Kaidy, Huschyar A1 - Kuthan, Kai A1 - Hering, Thomas A1 - Tippkötter, Nils T1 - Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation JF - Journal of Visualized Experiments N2 - For the successful implementation of microfluidic reaction systems, such as PCR and electrophoresis, the movement of small liquid volumes is essential. In conventional lab-on-a-chip-platforms, solvents and samples are passed through defined microfluidic channels with complex flow control installations. The droplet actuation platform presented here is a promising alternative. With it, it is possible to move a liquid drop (microreactor) on a planar surface of a reaction platform (lab-in-a-drop). The actuation of microreactors on the hydrophobic surface of the platform is based on the use of magnetic forces acting on the outer shell of the liquid drops which is made of a thin layer of superhydrophobic magnetite particles. The hydrophobic surface of the platform is needed to avoid any contact between the liquid core and the surface to allow a smooth movement of the microreactor. On the platform, one or more microreactors with volumes of 10 µL can be positioned and moved simultaneously. The platform itself consists of a 3 x 3 matrix of electrical double coils which accommodate either neodymium or iron cores. The magnetic field gradients are automatically controlled. By variation of the magnetic field gradients, the microreactors' magnetic hydrophobic shell can be manipulated automatically to move the microreactor or open the shell reversibly. Reactions of substrates and corresponding enzymes can be initiated by merging the microreactors or bringing them into contact with surface immobilized catalysts. Y1 - 2016 U6 - http://dx.doi.org/10.3791/54643 SN - 1940-087X IS - Issue 126 ER - TY - JOUR A1 - Wulfhorst, Helene A1 - Duwe, Anna-Maria A1 - Merseburg, Johannes A1 - Tippkötter, Nils T1 - Compositional analysis of pretreated (beech) wood using differential scanning calorimetry and multivariate data analysis JF - Tetrahedron N2 - The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.tet.2016.04.029 VL - 72 IS - 46 SP - 7329 EP - 7334 PB - Elsevier CY - Amsterdam ER - TY - CHAP A1 - Engel, M. A1 - Thieringer, J. A1 - Tippkötter, Nils T1 - Microbial electrosynthesis for sustainable biobutanol production T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 77 EP - 78 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Hering, T. A1 - Ulber, Roland A1 - Tippkötter, Nils T1 - Development of a screening system for antimicrobial surfaces T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 129 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Roth, J. A1 - Möhring, S. A1 - Tippkötter, Nils T1 - Characterization and evaluation of lignocellulosic biomass 130 hydrolysates for ABE fermentation T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 130 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Möhring, S. A1 - Wulfhorst, H. A1 - Roth, J. A1 - Tippkötter, Nils T1 - Pretreatment strategies for lignocellulosic biomass T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 131 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Capitain, C. A1 - Hering, T. A1 - Tippkötter, Nils A1 - Ulber, R. T1 - Enzymatic polymerization of lignin model compounds and solubilized lignin in an aqueous ethanol extract T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 151 EP - 152 PB - DECHEMA CY - Frankfurt am Main ER - TY - CHAP A1 - Wulfhorst, H. A1 - Duwe, A. A1 - Möhring, S. A1 - Jurca, O. A1 - Tippkötter, Nils T1 - Analysis of pretreated biomass by differential scanning 132 calorimetry and multivariate data analysis T2 - New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany Y1 - 2016 SP - 132 PB - DECHEMA CY - Frankfurt am Main ER - TY - JOUR A1 - Paulßen, Elisabeth A1 - Lengkeek, Nigel A. A1 - Le, Van So A1 - Pellegrini, Paul A. A1 - Greguric, Ivan A1 - Weiner, Ron T1 - The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [⁶⁸Ga(DOTATATE)] JF - Applied Radiation and Isotopes N2 - [⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.apradiso.2015.09.008 SN - 1872-9800 VL - 107 SP - 13 EP - 16 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Infantino, Angelo A1 - Paulßen, Elisabeth A1 - Mostacci, Domiziano A1 - Schaffer, Paul A1 - Trinczek, Michael A1 - Hoehr, Cornelia T1 - Assessment of the production of medical isotopes using the Monte Carlo code FLUKA: Simulations against experimental measurements JF - Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms N2 - The Monte Carlo code FLUKA is used to simulate the production of a number of positron emitting radionuclides, ¹⁸F, ¹³N, ⁹⁴Tc, ⁴⁴Sc, ⁶⁸Ga, ⁸⁶Y, ⁸⁹Zr, ⁵²Mn, ⁶¹Cu and ⁵⁵Co, on a small medical cyclotron with a proton beam energy of 13 MeV. Experimental data collected at the TR13 cyclotron at TRIUMF agree within a factor of 0.6 ± 0.4 with the directly simulated data, except for the production of ⁵⁵Co, where the simulation underestimates the experiment by a factor of 3.4 ± 0.4. The experimental data also agree within a factor of 0.8 ± 0.6 with the convolution of simulated proton fluence and cross sections from literature. Overall, this confirms the applicability of FLUKA to simulate radionuclide production at 13 MeV proton beam energy. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.nimb.2015.10.067 SN - 1872-9584 VL - 366 SP - 117 EP - 123 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Zhang, Jin A1 - Heimbach, Tycho A1 - Scheer, Nico A1 - Barve, Avantika A1 - Li, Wenkui A1 - Lin, Wen A1 - He, Handan T1 - Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4–Humanized Mouse Studies With PBPK Modeling JF - Journal of Pharmaceutical Sciences N2 - NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir. Y1 - 2016 U6 - http://dx.doi.org/doi.org/10.1016/j.xphs.2016.01.021 SN - 0022-3549 VL - Volume 105 IS - Issue 4 SP - 1398 EP - 1404 PB - Elsevier CY - Amsterdam ER -