@article{HenkenOosterhuisOehlschlaegeretal.2012, author = {Henken, F. E. and Oosterhuis, K. and {\"O}hlschl{\"a}ger, Peter and Bosch, L. and Hooijberg, E. and Haanen, J. B. A. G. and Steenbergen, R. D. M.}, title = {Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7}, series = {Vaccine}, volume = {30}, journal = {Vaccine}, number = {28}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0264-410X}, doi = {10.1016/j.vaccine.2012.04.013}, pages = {4259 -- 4266}, year = {2012}, abstract = {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.}, language = {en} } @article{ImmelGruetzkeSpaeteetal.2012, author = {Immel, Timo and Gr{\"u}tzke, Martin and Sp{\"a}te, Anne-Katrin and Groth, Ulrich and {\"O}hlschl{\"a}ger, Peter and Huhn, Thomas}, title = {Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy}, series = {Chemical Communications}, volume = {48}, journal = {Chemical Communications}, number = {46}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1364-548X}, doi = {10.1039/C2CC31624B}, pages = {5790 -- 5792}, year = {2012}, abstract = {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.}, language = {en} } @article{PaulssenKongArciszewskietal.2012, author = {Paulßen, Elisabeth and Kong, Shushu and Arciszewski, Pawel and Wielbalck, Swantje and Abram, Ulrich}, title = {Aryl and NHC Compounds of Technetium and Rhenium}, series = {Journal of the American Chemical Society}, volume = {134}, journal = {Journal of the American Chemical Society}, number = {22}, publisher = {ACS Publications}, address = {Washington, DC}, issn = {1520-5126}, doi = {10.1021/ja3033718}, pages = {9118 -- 9121}, year = {2012}, abstract = {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.}, language = {en} } @article{PaulssenNgyugenKahlckeetal.2012, author = {Paulßen, Elisabeth and Ngyugen, Hung Huy and Kahlcke, Nils and Deflon, Victor M. and Abram, Ulrich}, title = {Tricarbonyltechnetium(I) and -rhenium(I) complexes with N′-thiocarbamoylpicolylbenzamidines}, series = {Polyhedron}, volume = {40}, journal = {Polyhedron}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0277-5387}, doi = {10.1016/j.poly.2012.04.008}, pages = {153 -- 158}, year = {2012}, abstract = {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.}, language = {en} } @article{ScheerBalimaneHaywardetal.2012, author = {Scheer, Nico and Balimane, Praveen and Hayward, Michael D. and Buechel, Sandra and Kauselmann, Gunther and Wolf, C. Roland}, title = {Generation and Characterization of a Novel Multidrug Resistance Protein 2 Humanized Mouse Line}, series = {Drug Metabolism and Disposition}, volume = {40}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/dmd.112.047605}, pages = {2212 -- 2218}, year = {2012}, abstract = {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.}, language = {en} } @article{ScheerKapelyukhRodeetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Buechel, Sandra and Wolf, C. Roland}, title = {Generation and characterization of novel cytochrome P450 Cyp2c gene cluster knockout and CYP2C9 humanized mouse lines}, series = {Molecular Pharmacology}, volume = {82}, journal = {Molecular Pharmacology}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.112.080036}, pages = {1022 -- 1029}, year = {2012}, abstract = {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.}, language = {en} } @article{LempiaeinenCouttetBolognanietal.2012, author = {Lempi{\"a}inen, Harri and Couttet, Philippe and Bolognani, Federico and M{\"u}ller, Arne and Dubost, Val{\´e}rie and Luisier, Rapha{\"e}lle and Rio-Espinola, Alberto del and Vitry, Veronique and Unterberger, Elif B. and Thomson, John P. and Treindl, Fridolin and Metzger, Ute and Wrzodek, Clemens and Hahne, Florian and Zollinger, Tulipan and Brasa, Sarah and Kalteis, Magdalena and Marcellin, Magali and Giudicelli, Fanny and Braeuning, Albert and Morawiec, Laurent and Zamurovic, Natasa and L{\"a}ngle, Ulrich and Scheer, Nico and Sch{\"u}beler, Dirk and Goodman, Jay and Chibout, Salah-Dine and Marlowe, Jennifer and Theil, Dietlinde and Heard, David J. and Grenet, Olivier and Zell, Andreas and Templin, Markus F. and Meehan, Richard R. and Wolf, Roland C. and Elcombe, Clifford R. and Schwarz, Michael and Moulin, Pierre and Terranova, R{\´e}mi and Moggs, Jonathan G.}, title = {Identification of Dlk1-Dio3 imprinted gene cluster non-coding RNAs as novel candidate biomarkers for liver tumor promotion}, series = {Toxicological Sciences}, volume = {131}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {10.1093/toxsci/kfs303}, pages = {375 -- 386}, year = {2012}, abstract = {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.}, language = {en} } @article{ScheerKapelyukhMcEwanetal.2012, author = {Scheer, Nico and Kapelyukh, Yury and McEwan, Jillian and Beuger, Vincent and Stanley, Lesley A. and Rode, Anja and Wolf, C. Roland}, title = {Modeling Human Cytochrome P450 2D6 Metabolism and Drug-drug Interaction by a Novel Panel of Knockout and Humanized Mouse Lines}, series = {Molecular Pharmacology}, volume = {81}, journal = {Molecular Pharmacology}, number = {1}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.075192}, pages = {63 -- 72}, year = {2012}, abstract = {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.}, language = {en} } @article{SchiffelsPinkenburgScheldenetal.2013, author = {Schiffels, Johannes and Pinkenburg, Olaf and Schelden, Maximilian and Aboulnaga, El-Hussiny A. A. and Baumann, Marcus and Selmer, Thorsten}, title = {An innovative cloning platform enables large-scale production and maturation of an oxygen-tolerant [NiFe]-hydrogenase from cupriavidus necator in Escherichia coli}, series = {PLOS one. 2013}, journal = {PLOS one. 2013}, publisher = {Public Library of Science}, address = {San Francisco, California}, issn = {1932-6203}, doi = {10.1371/journal.pone.0068812}, year = {2013}, language = {en} } @article{AbulnagaPinkenburgSchiffelsetal.2013, author = {Abulnaga, El-Hussiny and Pinkenburg, Olaf and Schiffels, Johannes and E-Refai, Ahmed and Buckel, Wolfgang and Selmer, Thorsten}, title = {Effect of an Oxygen-Tolerant Bifurcating Butyryl Coenzyme A Dehydrogenase/Electron-Transferring Flavoprotein Complex from Clostridium difficile on Butyrate Production in Escherichia coli}, series = {Journal of bacteriology}, volume = {195}, journal = {Journal of bacteriology}, number = {16}, issn = {1098-5530 [E-Journal]}, pages = {3704 -- 3713}, year = {2013}, language = {en} } @article{ScheeleOertelBongaertsetal.2013, author = {Scheele, Sandra and Oertel, Dan and Bongaerts, Johannes and Evers, Stefan and Hellmuth, Hendrik and Maurer, Karl-Heinz and Bott, Michael and Freudl, Roland}, title = {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}, series = {Microbial biotechnology}, journal = {Microbial biotechnology}, publisher = {Wiley-Blackwell}, address = {Oxford}, issn = {1751-7915}, pages = {202 -- 206}, year = {2013}, language = {en} } @article{WilmingBegemannKuhneetal.2013, author = {Wilming, Anja and Begemann, Jens and Kuhne, Stefan and Regestein, Lars and Bongaerts, Johannes and Evers, Stefan and Maurer, Karl-Heinz and B{\"u}chs, Jochen}, title = {Metabolic studies of γ-polyglutamic acid production in Bacillus licheniformis by small-scale continuous cultivations}, series = {Biochemical engineering journal}, volume = {Vol. 73}, journal = {Biochemical engineering journal}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-295X (E-Journal); 1369-703X (Print)}, pages = {29 -- 37}, year = {2013}, language = {en} } @article{VoigtSchroeterJuergenetal.2013, author = {Voigt, Birgit and Schroeter, Rebecca and J{\"u}rgen, Britta and Albrecht, Dirk and Evers, Stefan and Bongaerts, Johannes and Maurer, Karl-Heinz and Schweder, Thomas and Hecker, Michael}, title = {The response of Bacillus licheniformis to heat and ethanol stress and the role of the SigB regulon}, series = {Proteomics}, volume = {Vol. 13}, journal = {Proteomics}, number = {Iss. 14}, publisher = {Wiley}, address = {Weinheim}, issn = {1615-9861 (E-Journal); 1615-9853 (Print)}, pages = {2140 -- 2146}, year = {2013}, language = {en} } @article{RachingerBauchStrittmatteretal.2013, author = {Rachinger, Michael and Bauch, Melanie and Strittmatter, Axel and Bongaerts, Johannes and Evers, Stefan and Maurer, Karl-Heinz and Daniel, Rolf and Liebl, Wolfgang and Liesegang, Heiko and Ehrenreich, Armin}, title = {Size unlimited markerless deletions by a transconjugative plasmid-system in Bacillus licheniformis}, series = {Journal of biotechnology}, volume = {Vol. 164}, journal = {Journal of biotechnology}, number = {Iss. 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, pages = {365 -- 369}, year = {2013}, language = {en} } @article{WiegandDietrichHerteletal.2013, author = {Wiegand, Sandra and Dietrich, Sascha and Hertel, Robert and Bongaerts, Johannes and Evers, Stefan and Volland, Sonja and Daniel, Rolf and Liesegang, Heiko}, title = {RNA-Seq of Bacillus licheniformis: active regulatory RNA features expressed within a productive fermentation}, series = {BMC genomics}, volume = {Vol. 14}, journal = {BMC genomics}, publisher = {BioMed Central}, address = {London}, issn = {1471-2164}, pages = {667}, year = {2013}, language = {en} } @article{DuttaHartkopfFroederWitteetal.2013, author = {Dutta, Suryendu and Hartkopf-Fr{\"o}der, Christoph and Witte, Karin and Brocke, Rainer and Mann, Ulrich}, title = {Molecular characterization of fossil palynomorphs by transmission micro-FTIR spectroscopy: implications for hydrocarbon source evaluation}, series = {International journal of coal geology}, volume = {Vol. 115}, journal = {International journal of coal geology}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-7840 (E-Journal); 0166-5162 (Print)}, pages = {13 -- 23}, year = {2013}, language = {en} } @inproceedings{TakenagaHerreraWerneretal.2013, author = {Takenaga, Shoko and Herrera, Cony F. and Werner, Frederik and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten}, title = {Detection of the metabolic activity of cells by differential measurements based on a single light-addressable potentiometric sensor chip}, series = {11. Dresdner Sensor-Symposium : 9.-11.12.2013}, booktitle = {11. Dresdner Sensor-Symposium : 9.-11.12.2013}, organization = {Dresdner Sensor-Symposium <11, 2013>}, isbn = {978-3-9813484-5-3}, pages = {63 -- 67}, year = {2013}, language = {en} } @article{MartinezJakobTuetal.2013, author = {Martinez, Ronny and Jakob, Felix and Tu, Ran and Siegert, Petra and Maurer, Karl-Heinz and Schwaneberg, Ulrich}, title = {Increasing activity and thermal resistance of Bacillus gibsonii alkaline protease (BgAP) by directed evolution}, series = {Biotechnology and bioengineering}, volume = {Vol. 110}, journal = {Biotechnology and bioengineering}, number = {Iss. 3}, publisher = {Wiley}, address = {Weinheim}, issn = {1097-0290 (E-Journal); 0006-3592 (Print); 0368-1467 (Print)}, pages = {711 -- 720}, year = {2013}, language = {en} } @article{JakobMartinezMandaweetal.2013, author = {Jakob, Felix and Martinez, Ronny and Mandawe, John and Hellmuth, Hendrik and Siegert, Petra and Maurer, Karl-Heinz and Schwaneberg, Ulrich}, title = {Surface charge engineering of a Bacillus gibsonii subtilisin protease}, series = {Applied microbiology and biotechnology}, volume = {Vol. 97}, journal = {Applied microbiology and biotechnology}, number = {Iss. 15}, publisher = {Springer}, address = {Berlin}, issn = {1432-0614 (E-Journal); 0171-1741 (Print); 0175-7598 (Print); 0340-2118 (Print)}, pages = {6793 -- 6802}, year = {2013}, language = {en} } @article{ScheerSnaithWolfetal.2013, author = {Scheer, Nico and Snaith, Mike and Wolf, C. Roland and Seibler, Jost}, title = {Generation and utility of genetically humanized mouse models}, series = {Drug Discovery Today}, volume = {Vol 18}, journal = {Drug Discovery Today}, number = {23-24}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1359-6446}, doi = {10.1016/j.drudis.2013.07.007}, pages = {1200 -- 1211}, year = {2013}, language = {en} } @article{BouwmanGuldenHeijdenetal.2013, author = {Bouwman, Peter and Gulden, Hanneke van der and Heijden, Ingrid van der and Drost, Rinske and Klijn, Christiaan N. and Prasetyanti, Pramudita and Pieterse, Mark and Wientjens, Ellen and Seibler, Jost and Hogervorst, Frank B. L. and Jonkers, Jos}, title = {A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants}, series = {Cancer Discovery}, journal = {Cancer Discovery}, number = {3}, issn = {2159-8290}, doi = {10.1158/2159-8290.CD-13-0094}, pages = {1142 -- 1152}, year = {2013}, language = {en} } @article{MichalakNacerddinePietersenetal.2013, author = {Michalak, Ewa Malgorzata and Nacerddine, Karim and Pietersen, Alexandra and Beuger, Vincent and Pawlitzky, Inka and Cornelissen-Steijger, Paulien and Wientjens, Ellen and Tanger, Ellen and Seibler, Jost and Lohuizen, Maarten van and Jonkers, Jos}, title = {Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool}, series = {Stem Cells}, volume = {Vol 31}, journal = {Stem Cells}, number = {9}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1549-4918}, doi = {10.1002/stem.1437}, pages = {1910 -- 1920}, year = {2013}, language = {en} } @article{GebeshuberKornauthDongetal.2013, author = {Gebeshuber, Christoph A. and Kornauth, Christoph and Dong, Lihua and Sierig, Ralph and Seibler, Jost and Reiss, Martina and Tauber, Stefanie and Bilban, Martin and Wang, Shijun and Kain, Renate and B{\"o}hmig, Georg A. and Moeller, Marcus J. and Gr{\"o}ne, Hermann-Josef and Englert, Christoph and Martinez, Javier and Kerjaschki, Dontscho}, title = {Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1}, series = {Nature Medicine}, volume = {19}, journal = {Nature Medicine}, number = {4}, issn = {1078-8956}, doi = {10.1038/nm.3142}, pages = {481 -- 487}, year = {2013}, language = {en} } @article{KornfeldBaitzelKoenneretal.2013, author = {Kornfeld, Jan-Wilhelm and Baitzel, Catherina and K{\"o}nner, A. Christine and Nicholls, Hayley T. and Vogt, Merly C. and Herrmanns, Karolin and Scheja, Ludger and Haumaitre, C{\´e}cile and Wolf, Anna M. and Knippschild, Uwe and Seibler, Jost and Cereghini, Silvia and Heeren, Joerg and Stoffel, Markus and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b}, series = {Nature}, volume = {494}, journal = {Nature}, number = {7435}, publisher = {Springer Nature}, address = {Cham}, isbn = {0028-0836}, doi = {10.1038/nature11793}, pages = {111 -- 115}, year = {2013}, language = {en} } @article{WiegandVoigtAlbrechtetal.2013, author = {Wiegand, Sandra and Voigt, Birgit and Albrecht, Dirk and Bongaerts, Johannes and Evers, Stefan and Hecker, Michael and Daniel, Rolf and Liesegang, Heiko}, title = {Fermentation stage-dependent adaptations of Bacillus licheniformis during enzyme production}, series = {Microbial Cell Factories}, volume = {12}, journal = {Microbial Cell Factories}, publisher = {Biomed Central}, address = {London}, issn = {1475-2859}, doi = {10.1186/1475-2859-12-120}, pages = {120}, year = {2013}, language = {en} } @article{ThielTippkoetterSucketal.2013, author = {Thiel, Alexander and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland}, title = {New zeolite adsorbents for downstream processing of polyphenols from renewable resources}, series = {Engineering in Life Sciences}, volume = {13}, journal = {Engineering in Life Sciences}, number = {3}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/elsc.201200188}, pages = {239 -- 246}, year = {2013}, abstract = {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.}, language = {en} } @article{TippkoetterAlKaidyWollnyetal.2013, author = {Tippk{\"o}tter, Nils and Al-Kaidy, Huschyar and Wollny, Steffen and Ulber, Roland}, title = {Functionalized magnetizable particles for downstream processing in single-use systems}, series = {Chemie Ingenieur Technik}, volume = {85}, journal = {Chemie Ingenieur Technik}, number = {1-2: Special Issue: Single-Use Technology}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/cite.201200130}, pages = {76 -- 86}, year = {2013}, abstract = {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.}, language = {en} } @misc{AlKaidyTippkoetterUlber2013, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {A system and a method for the implementation of chemical, biological or physical reactions [Europ{\"a}ische Patentanmeldung]}, publisher = {Europ{\"a}isches Patentamt}, address = {Den Hague}, pages = {16 Seiten}, year = {2013}, abstract = {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.}, language = {en} } @misc{StadtmuellerTippkoetterUlber2013, author = {Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {A method for production of single-stranded nucleic acids [Europ{\"a}ische Patentanmeldung]}, publisher = {Europ{\"a}isches Patentamt}, address = {Den Hague}, pages = {14 Seiten}, year = {2013}, language = {en} } @article{PellegriniHowellShepherdetal.2013, author = {Pellegrini, Paul A. and Howell, Nicholas R. and Shepherd, Rachael K. and Lengkeek, Nigel A. and Paulßen, Elisabeth and Katsifis, Andrew G. and Greguric, Ivan}, title = {Synthesis and Radiolabelling of DOTA-Linked Glutamine Analogues with 67,68Ga as Markers for Increased Glutamine Metabolism in Tumour Cells}, series = {Molecules}, volume = {18}, journal = {Molecules}, number = {6}, publisher = {MDPI}, address = {Basel}, issn = {1420-3049}, doi = {10.3390/molecules18067160}, pages = {7160 -- 7178}, year = {2013}, language = {en} } @article{PaulssenLeLengkeeketal.2013, author = {Paulßen, Elisabeth and Le, Van So and Lengkeek, Nigel and Pellegrini, Paul and Jackson, Tim and Greguric, Ivan and Weiner, Ron}, title = {Influence of Metal Ions on the 68Ga-labeling of DOTATATE}, series = {Applied Radiation and Isotopes}, volume = {82}, journal = {Applied Radiation and Isotopes}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9800}, doi = {10.1016/j.apradiso.2013.08.010}, pages = {232 -- 238}, year = {2013}, language = {en} } @article{ScheerWolf2013, author = {Scheer, Nico and Wolf, C. Roland}, title = {Xenobiotic receptor humanized mice and their utility}, series = {Drug Metabolism Reviews}, journal = {Drug Metabolism Reviews}, number = {1}, publisher = {Taylor \& Francis}, address = {London}, issn = {1097-9883}, doi = {10.3109/03602532.2012.738687}, pages = {110 -- 121}, year = {2013}, language = {en} } @article{HuckSchiffelsHerreraetal.2013, author = {Huck, Christina and Schiffels, Johannes and Herrera, Cony N. and Schelden, Maximilian and Selmer, Thorsten and Poghossian, Arshak and Baumann, Marcus and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Metabolic responses of Escherichia coli upon glucose pulses captured by a capacitive field-effect sensor}, series = {Physica Status Solidi (A)}, volume = {210}, journal = {Physica Status Solidi (A)}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0031-8965}, doi = {10.1002/pssa.201200900}, pages = {926 -- 931}, year = {2013}, abstract = {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.}, language = {en} } @article{BaeckerRakowskiPoghossianetal.2013, author = {B{\"a}cker, Matthias and Rakowski, D. and Poghossian, Arshak and Biselli, Manfred and Wagner, Patrick and Sch{\"o}ning, Michael Josef}, title = {Chip-based amperometric enzyme sensor system for monitoring of bioprocesses by flow-injection analysis}, series = {Journal of Biotechnology}, volume = {163}, journal = {Journal of Biotechnology}, number = {4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0168-1656}, doi = {10.1016/j.jbiotec.2012.03.014}, pages = {371 -- 376}, year = {2013}, abstract = {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.}, language = {en} } @article{WincklerKruegerSchnitzleretal.2014, author = {Winckler, Silvia and Krueger, Rolf and Schnitzler, Thomas and Zang, Werner and Fischer, Rainer and Biselli, Manfred}, title = {A sensitive monitoring system for mammalian cell cultivation processes: a PAT approach}, series = {Bioprocess and biosystems engineering}, volume = {37}, journal = {Bioprocess and biosystems engineering}, number = {5}, publisher = {Springer}, address = {Berlin, Heidelberg}, issn = {1615-7591 (Print) 1615-7605 (Online)}, doi = {10.1007/s00449-013-1062-8}, pages = {901 -- 912}, year = {2014}, abstract = {Biopharmaceuticals such as antibodies are produced in cultivated mammalian cells, which must be monitored to comply with good manufacturing practice. We, therefore, developed a fully automated system comprising a specific exhaust gas analyzer, inline analytics and a corresponding algorithm to precisely determine the oxygen uptake rate, carbon dioxide evolution rate, carbon dioxide transfer rate, transfer quotient and respiratory quotient without interrupting the ongoing cultivation, in order to assess its reproducibility. The system was verified using chemical simulation experiments and was able to measure the respiratory activity of hybridoma cells and DG44 cells (derived from Chinese hamster ovary cells) with satisfactory results at a minimum viable cell density of ~2.0 × 10⁵ cells ml⁻¹. The system was suitable for both batch and fed-batch cultivations in bubble-aerated and membrane-aerated reactors, with and without the control of pH and dissolved oxygen.}, language = {en} } @article{HeinzeMangPeteretal.2014, author = {Heinze, Daniel and Mang, Thomas and Peter, Karin and M{\"o}ller, Martin and Weichold, Oliver}, title = {Synthesis of low molecular weight poly(vinyl acetate) and its application as plasticizer}, series = {Journal of applied polymer science}, volume = {131}, journal = {Journal of applied polymer science}, number = {9}, publisher = {Wiley}, address = {New York}, issn = {1097-4628 (E-Journal); 0021-8995 (Print)}, doi = {10.1002/app.40226}, pages = {Article No. 40226}, year = {2014}, abstract = {Poly(vinyl acetate), PVAc, with a degree of polymerization Xn = 10 was prepared by chain-transfer radical polymerization using carbon tetrachloride and used as oligomeric plasticizer for commercial PVAc. However, the chlorinated chain ends cause a low thermal stability requiring mild Cl/H substitution. The product exhibits high thermal stability and excellent melt-compounding properties. Blends of oligomeric and commercial PVAc show single glass transition temperatures which decrease with higher oligomer content and exhibit small negative deviations from Fox' linear additivity rule. This indicates plasticization and miscibility being mainly due to entropic effects. Injection-moulded thick specimens show ductile behaviour at oligomer contents >10 wt \%, while sheets with a thickness of 0.2-0.5 mm appear flexible already at 7.5 wt \%. The oxygen permeability coefficients are an order of magnitude lower than those of low-density polyethylene. Due to the sum of their properties, the plasticized sheets present a promising alternative in the preparation of barrier materials.}, language = {en} } @article{WangDruckenmuellerElbersetal.2014, author = {Wang, Ren-Qi and Druckenm{\"u}ller, Katharina and Elbers, Gereon and Guenther, Klaus and Crou{\´e}, Jean-Philippe}, title = {Analysis of aquatic-phase natural organic matter by optimized LDI-MS method}, series = {Journal of mass spectrometry}, volume = {49}, journal = {Journal of mass spectrometry}, number = {2}, publisher = {Wiley}, address = {Bognor Regis}, issn = {1096-9888}, doi = {10.1002/jms.3321}, pages = {154 -- 160}, year = {2014}, abstract = {The composition and physiochemical properties of aquatic-phase natural organic matter (NOM) are most important problems for both environmental studies and water industry. Laser desorption/ionization (LDI) mass spectrometry facilitated successful examinations of NOM, as humic and fulvic acids in NOM are readily ionized by the nitrogen laser. In this study, hydrophobic NOMs (HPO NOMs) from river, reservoir and waste water were characterized by this technique. The effect of analytical variables like concentration, solvent composition and laser energy was investigated. The exact masses of small molecular NOM moieties in the range of 200-1200 m/z were determined in reflectron mode. In addition, spectra of post-source-decay experiments in this range showed that some compounds from different natural NOMs had the same fragmental ions. In the large mass range of 1200-15 000 Da, macromolecules and their aggregates were found in HPO NOMs from natural waters. Highly humic HPO exhibited mass peaks larger than 8000 Da. On the other hand, the waste water and reservoir water mainly had relatively smaller molecules of about 2000 Da. The LDI-MS measurements indicated that highly humic river waters were able to form large aggregates and membrane foulants, while the HPO NOMs from waste water and reservoir water were unlikely to form large aggregates. Copyright © 2014 John Wiley \& Sons, Ltd.}, language = {en} } @article{HeineHerrmannSelmeretal.2014, author = {Heine, A. and Herrmann, G. and Selmer, Thorsten and Terwesten, F. and Buckel, W. and Reuter, K.}, title = {High resolution crystal structure of clostridium propionicum β-Alanyl-CoA:Ammonia Lyase, a new member of the "Hot Dog Fold" protein superfamily}, series = {Proteins}, volume = {82}, journal = {Proteins}, number = {9}, publisher = {Wiley-Liss}, address = {New York}, issn = {1097-0134 (E-Journal); 0887-3585 (Print)}, doi = {10.1002/prot.24557}, pages = {2041 -- 2053}, year = {2014}, abstract = {Clostridium propionicum is the only organism known to ferment β-alanine, a constituent of coenzyme A (CoA) and the phosphopantetheinyl prosthetic group of holo-acyl carrier protein. The first step in the fermentation is a CoA-transfer to β-alanine. Subsequently, the resulting β-alanyl-CoA is deaminated by the enzyme β-alanyl-CoA:ammonia lyase (Acl) to reversibly form ammonia and acrylyl-CoA. We have determined the crystal structure of Acl in its apo-form at a resolution of 0.97 {\AA} as well as in complex with CoA at a resolution of 1.59 {\AA}. The structures reveal that the enyzme belongs to a superfamily of proteins exhibiting a so called "hot dog fold" which is characterized by a five-stranded antiparallel β-sheet with a long α-helix packed against it. The functional unit of all "hot dog fold" proteins is a homodimer containing two equivalent substrate binding sites which are established by the dimer interface. In the case of Acl, three functional dimers combine to a homohexamer strongly resembling the homohexamer formed by YciA-like acyl-CoA thioesterases. Here, we propose an enzymatic mechanism based on the crystal structure of the Acl·CoA complex and molecular docking. Proteins 2014; 82:2041-2053. © 2014 Wiley Periodicals, Inc.}, language = {en} } @article{TakenagaBiselliSchnitzleretal.2014, author = {Takenaga, Shoko and Biselli, Manfred and Schnitzler, Thomas and {\"O}hlschl{\"a}ger, Peter and Wagner, Torsten and Sch{\"o}ning, Michael Josef}, title = {Toward multi-analyte bioarray sensors: LAPS-based on-chip determination of a Michaelis-Menten-like kinetics for cell culturing}, series = {Physica status solidi A : Applications and materials science}, volume = {211}, journal = {Physica status solidi A : Applications and materials science}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1521-396X (E); 1862-6319 (E-Journal); 0031-8965 (Print); 1862-6300 (Print)}, doi = {10.1002/pssa.201330464}, pages = {1410 -- 1415}, year = {2014}, abstract = {The metabolic activity of Chinese hamster ovary (CHO) cells was observed using a light-addressable potentiometric sensor (LAPS). The dependency toward different glucose concentrations (17-200 mM) follows a Michaelis-Menten kinetics trajectory with Kₘ = 32.8 mM, and the obtained Kₘ value in this experiment was compared with that found in literature. In addition, the pH shift induced by glucose metabolism of tumor cells transfected with the HPV-16 genome (C3 cells) was successfully observed. These results indicate the possibility to determine the tumor cells metabolism with a LAPS-based measurement device.}, language = {en} } @article{WhiteheadOehlschlaegerAlmajhdietal.2014, author = {Whitehead, Mark and {\"O}hlschl{\"a}ger, Peter and Almajhdi, Fahad N. and Alloza, Leonor and Marz{\´a}bal, Pablo and Meyers, Ann E. and Hitzeroth, Inga I. and Rybicki, Edward P.}, title = {Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice}, series = {BMC cancer}, journal = {BMC cancer}, number = {14:367}, publisher = {BioMed Central}, address = {London}, issn = {1471-2407}, doi = {10.1186/1471-2407-14-367}, pages = {1 -- 15}, year = {2014}, language = {en} } @article{KueppersSteffenHellmuthetal.2014, author = {K{\"u}ppers, Tobias and Steffen, Victoria and Hellmuth, Hendrik and O'Connell, Timothy and Bongaerts, Johannes and Maurer, Karl-Heinz and Wiechert, Wolfgang}, title = {Developing a new production host from a blueprint: Bacillus pumilus as an industrial enzyme producer}, series = {Microbial cell factories}, volume = {13}, journal = {Microbial cell factories}, publisher = {BioMed Central}, address = {London}, issn = {1475-2859 (E-Journal)}, doi = {10.1186/1475-2859-13-46}, pages = {Article No. 46}, year = {2014}, language = {en} } @article{GuoMiyamotoWagneretal.2014, author = {Guo, Yuanyuan and Miyamoto, Ko-ichiro and Wagner, Torsten and Sch{\"o}ning, Michael Josef and Yoshinobu, Tatsuo}, title = {Theoretical study and simulation of light-addressable potentiometric sensors}, series = {Physica status solidi (A) : applications and materials}, volume = {211}, journal = {Physica status solidi (A) : applications and materials}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {0031-8965}, doi = {10.1002/pssa.201330354}, pages = {1467 -- 1472}, year = {2014}, abstract = {The light-addressable potentiometric sensor (LAPS) is a semiconductor-based potentiometric sensor using a light probe with an ability of detecting the concentration of biochemical species in a spatially resolved manner. As an important biomedical sensor, research has been conducted to improve its performance, for instance, to realize high-speed measurement. In this work, the idea of facilitating the device-level simulation, instead of using an equivalent-circuit model, is presented for detailed analysis and optimization of the performance of the LAPS. Both carrier distribution and photocurrent response have been simulated to provide new insight into both amplitude-mode and phase-mode operations of the LAPS. Various device parameters can be examined to effectively design and optimize the LAPS structures and setups for enhanced performance.}, language = {en} } @article{RatkeMilowLisinskietal.2014, author = {Ratke, Lorenz and Milow, Barbara and Lisinski, Susanne and Hoepfner, Sandra}, title = {On an effect of fine ceramic particles on the structure of aerogels}, series = {Microgravity science and technology}, volume = {26}, journal = {Microgravity science and technology}, publisher = {Springer Nature}, address = {Heidelberg}, issn = {0938-0108 ; 1875-0494}, doi = {10.1007/s12217-014-9380-2}, pages = {103 -- 110}, year = {2014}, language = {en} } @article{HandtkeVollandMethlingetal.2014, author = {Handtke, Stefan and Volland, Sonja and Methling, Karen and Albrecht, Dirk and Becher, D{\"o}rte and Nehls, Jenny and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Liesegang, Heiko and Voigt, Birgit and Daniel, Rolf and Hecker, Michael}, title = {Cell physiology of the biotechnological relevant bacterium Bacillus pumilus - An omics-based approach}, series = {Journal of Biotechnology}, journal = {Journal of Biotechnology}, number = {192(A)}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2014.08.028}, pages = {204 -- 214}, year = {2014}, abstract = {Members of the species Bacillus pumilus get more and more in focus of the biotechnological industry as potential new production strains. Based on exoproteome analysis, B. pumilus strain Jo2, possessing a high secretion capability, was chosen for an omics-based investigation. The proteome and metabolome of B. pumilus cells growing either in minimal or complex medium was analyzed. In total, 1542 proteins were identified in growing B. pumilus cells, among them 1182 cytosolic proteins, 297 membrane and lipoproteins and 63 secreted proteins. This accounts for about 43\% of the 3616 proteins encoded in the B. pumilus Jo2 genome sequence. By using GC-MS, IP-LC/MS and H NMR methods numerous metabolites were analyzed and assigned to reconstructed metabolic pathways. In the genome sequence a functional secretion system including the components of the Sec- and Tat-secretion machinery was found. Analysis of the exoproteome revealed secretion of about 70 proteins with predicted secretion signals. In addition, selected production-relevant genome features such as restriction modification systems and NRPS clusters of B. pumilus Jo2 are discussed.}, language = {en} } @article{NachtrodtTietschMostaccietal.2014, author = {Nachtrodt, Frederik and Tietsch, Wolfgang and Mostacci, Domiziano and Scherer, Ulrich W.}, title = {Set-up and first operation of a plasma oven for treatment of low level radioactive wastes}, series = {Nuclear technology and radiation protection}, volume = {29}, journal = {Nuclear technology and radiation protection}, number = {Suppl.}, publisher = {VINČA Institute of Nuclear Sciences}, address = {Belgrad}, issn = {1451-3994}, doi = {10.2298/NTRP140SS47N}, pages = {47 -- 51}, year = {2014}, language = {en} } @article{RaueWambachGloeggleretal.2014, author = {Raue, Markus and Wambach, M. and Gl{\"o}ggler, S. and Grefen, Dana and Kaufmann, R. and Abetz, C. and Georgopanos, P. and Handge, U. A. and Mang, Thomas and Bl{\"u}mich, B. and Abetz, V.}, title = {Investigation of historical hard rubber ornaments of Charles Goodyear}, series = {Macromolecular chemistry and physics}, volume = {Vol. 215}, journal = {Macromolecular chemistry and physics}, number = {No. 3}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1022-1352}, pages = {245 -- 254}, year = {2014}, language = {en} } @article{PasteurTippkoetterKampeisetal.2014, author = {Pasteur, Aline and Tippk{\"o}tter, Nils and Kampeis, Percy and Ulber, Roland}, title = {Optimization of high gradient magnetic separation filter units for the purification of fermentation products}, series = {IEEE TRANSACTIONS ON MAGNETICS}, volume = {50}, journal = {IEEE TRANSACTIONS ON MAGNETICS}, number = {10}, publisher = {IEEE}, address = {New York, NY}, issn = {0018-9464}, doi = {10.1109/TMAG.2014.2325535}, pages = {Artikel 5000607}, year = {2014}, abstract = {High gradient magnetic separation (HGMS) has been established since the early 1970s. A more recent application of these systems is the use in bioprocesses. To integrate the HGMS in a fermentation process, it is necessary to optimize the separation matrix with regard to the magnetic separation characteristics and permeability of the non-magnetizable components of the fermentation broth. As part of the work presented here, a combined fluidic and magnetic force finite element model simulation was created using the software COMSOL Multiphysics and compared with separation experiments. Finally, as optimal lattice orientation of the separation matrix, a transversal rhombohedral arrangement was defined. The high suitability of the new filter matrix has been verified by separation experiments.}, language = {en} } @article{TippkoetterWollnySucketal.2014, author = {Tippk{\"o}tter, Nils and Wollny, Steffen and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland}, title = {Recycling of spent oil bleaching earth as source of glycerol for the anaerobic production of acetone, butanol, and ethanol with Clostridium diolis and lipolytic Clostridium lundense}, series = {Engineering in Life Sciences}, volume = {14}, journal = {Engineering in Life Sciences}, number = {4}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1618-2863}, doi = {10.1002/elsc.201300113}, pages = {425 -- 432}, year = {2014}, abstract = {A major part of edible oil is subjected to bleaching procedures, primarily with minerals applied as adsorbers. Their recycling is currently done either by regaining the oil via organic solvent extraction or by using the spent bleaching earth (SBE) as additive for animal feed, etc. As a new method, the reutilization of the by-product SBE for the microbiologic formation of acetone, butanol, and ethanol (ABE) is presented as proof-of-concept. The SBE was taken from a palm oil cleaning process. The recycling concept is based on the application of lipolytic clostridia strains. Due to considerably long fermentation times, co-fermentation with Candida rugosa and enzymatic hydrolyses of the bound oil with a subsequent clostridia fermentation are shown as alternative routes. Anaerobic fermentations under comparison of different clostridia strains were performed with glycerol media, enzymatically hydrolyzed palm oil and SBE. Solutes, side product compositions and productivities were quantified via HPLC. A successful production of ABE solutes from SBE has been done with a yield of 0.15 g butanol per gram of bound glycerol. Thus, the biotechnological recycling of the waste stream is possible in principle. Inhibition of the substrate suspension has been observed. A chromatographic ion-exchange of substrates increased the biomass concentration.}, language = {en} } @article{TippkoetterDuweWiesenetal.2014, author = {Tippk{\"o}tter, Nils and Duwe, Anna-Maria and Wiesen, Sebastian and Sieker, Tim and Ulber, Roland}, title = {Enzymatic hydrolysis of beech wood lignocellulose at high solid contents and its utilization as substrate for the production of biobutanol and dicarboxylic acids}, series = {Bioresource Technology}, volume = {167}, journal = {Bioresource Technology}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.biortech.2014.06.052}, pages = {447 -- 455}, year = {2014}, abstract = {The development of a cost-effective hydrolysis for crude cellulose is an essential part of biorefinery developments. To establish such high solid hydrolysis, a new solid state reactor with static mixing is used. However, concentrations >10\% (w/w) cause a rate and yield reduction of enzymatic hydrolysis. By optimizing the synergetic activity of cellulolytic enzymes at solid concentrations of 9\%, 17\% and 23\% (w/w) of crude Organosolv cellulose, glucose concentrations of 57, 113 and 152 g L⁻¹ are reached. However, the glucose yield decreases from 0.81 to 0.72gg⁻¹ at 17\% (w/w). Optimal conditions for hydrolysis scale-up under minimal enzyme addition are identified. As result, at 23\% (w/w) crude cellulose the glucose yield increases from 0.29 to 0.49gg⁻¹. As proof of its applicability, biobutanol, succinic and itaconic acid are produced with the crude hydrolysate. The potential of the substrate is proven e.g. by a high butanol yield of 0.33gg⁻¹.}, language = {en} } @article{HoehrPaulssenBenardetal.2014, author = {Hoehr, Cornelia and Paulßen, Elisabeth and Benard, Francois and Lee, Chris Jaeil and Hou, Xinchi and Badesso, Brian and Ferguson, Simon and Miao, Qing and Yang, Hua and Buckley, Ken and Hanemaayer, Victoire and Zeisler, Stefan and Ruth, Thomas and Celler, Anna and Schaffer, Paul}, title = {⁴⁴ᶢSc production using a water target on a 13 MeV cyclotron}, series = {Nuclear medicine and biology}, volume = {41}, journal = {Nuclear medicine and biology}, number = {5}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9614}, doi = {10.1016/j.nucmedbio.2013.12.016}, pages = {401 -- 406}, year = {2014}, abstract = {Access to promising radiometals as isotopes for novel molecular imaging agents requires that they are routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for the metal of interest is necessary, both of which can introduce significant hurdles in development of less common isotopes. Herein, we describe the production of ⁴⁴Sc (t₁⸝₂ = 3.97 h, Eavg,β⁺ = 1.47 MeV, branching ratio = 94.27\%) in a solution target and an automated loading system which allows a quick turn-around between different radiometallic isotopes and therefore greatly improves their availability for tracer development. Experimental yields are compared to theoretical calculations.}, language = {en} } @inproceedings{AlKaidyUlberTippkoetter2014, author = {Al-Kaidy, H. and Ulber, R. and Tippk{\"o}tter, Nils}, title = {A platform technology for the automated reaction control in magnetizable micro-fluidic droplets}, series = {Biomaterials - made in bioreactors : book of abstracts, May 26 - 28, 2014, Radisson Blu Park Hotel and Conference Dentre, Radebeul, Germany}, booktitle = {Biomaterials - made in bioreactors : book of abstracts, May 26 - 28, 2014, Radisson Blu Park Hotel and Conference Dentre, Radebeul, Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {21 -- 22}, year = {2014}, language = {en} } @article{LuisierLempiaeinenScherbichleretal.2014, author = {Luisier, Rapha{\"e}lle and Lempi{\"a}inen, Harri and Scherbichler, Nina and Braeuning, Albert and Geissler, Miriam and Dubost, Valerie and M{\"u}ller, Arne and Scheer, Nico and Chibout, Salah-Dine and Hara, Hisanori and Picard, Frank and Theil, Diethilde and Couttet, Philippe and Vitobello, Antonio and Grenet, Olivier and Grasl-Kraupp, Bettina and Ellinger-Ziegelbauer, Heidrung and Thomson, John P. and Meehan, Richard R. and Elcombe, Clifford R. and Henderson, Colin J. and Wolf, C. Roland and Schwarz, Michael and Moulin, Pierre and Terranova, Remi and Moggs, Jonathan G.}, title = {Phenobarbital Induces Cell Cycle Transcriptional Responses in Mouse Liver Humanized for Constitutive Androstane and Pregnane X Receptors}, series = {Toxicological Sciences}, volume = {139}, journal = {Toxicological Sciences}, number = {2}, publisher = {Oxford University Press}, address = {Oxford}, issn = {1094-2025}, doi = {https://doi.org/10.1093/toxsci/kfu038}, pages = {501 -- 511}, year = {2014}, abstract = {The constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) are closely related nuclear receptors involved in drug metabolism and play important roles in the mechanism of phenobarbital (PB)-induced rodent nongenotoxic hepatocarcinogenesis. Here, we have used a humanized CAR/PXR mouse model to examine potential species differences in receptor-dependent mechanisms underlying liver tissue molecular responses to PB. Early and late transcriptomic responses to sustained PB exposure were investigated in liver tissue from double knock-out CAR and PXR (CARᴷᴼ-PXRᴷᴼ), double humanized CAR and PXR (CARʰ-PXRʰ), and wild-type C57BL/6 mice. Wild-type and CARʰ-PXRʰ mouse livers exhibited temporally and quantitatively similar transcriptional responses during 91 days of PB exposure including the sustained induction of the xenobiotic response gene Cyp2b10, the Wnt signaling inhibitor Wisp1, and noncoding RNA biomarkers from the Dlk1-Dio3 locus. Transient induction of DNA replication (Hells, Mcm6, and Esco2) and mitotic genes (Ccnb2, Cdc20, and Cdk1) and the proliferation-related nuclear antigen Mki67 were observed with peak expression occurring between 1 and 7 days PB exposure. All these transcriptional responses were absent in CARᴷᴼ-PXRᴷᴼ mouse livers and largely reversible in wild-type and CARʰ-PXRʰ mouse livers following 91 days of PB exposure and a subsequent 4-week recovery period. Furthermore, PB-mediated upregulation of the noncoding RNA Meg3, which has recently been associated with cellular pluripotency, exhibited a similar dose response and perivenous hepatocyte-specific localization in both wild-type and CARʰ-PXRʰ mice. Thus, mouse livers coexpressing human CAR and PXR support both the xenobiotic metabolizing and the proliferative transcriptional responses following exposure to PB.}, language = {en} } @article{SalpatiChuChenetal.2014, author = {Salpati, Laurent and Chu, Xiaoyan and Chen, Liangfu and Prasad, Bhagwat and Dallas, Shannon and Evers, Raymond and Mamaril-Fishman, Donna and Geier, Ethan G. and Kehler, Jonathan and Kunta, Jeevan and Mezler, Mario and Laplanche, Loic and Pang, Jodie and Soars, Matthew G. and Unadkat, Jashvant D. and van Waterschoot, Robert A.B. and Yabut, Jocelyn and Schinkel, Alfred H. and Scheer, Nico and Rode, Anja}, title = {Evaluation of organic anion transporting polypeptide 1B1 and 1B3 humanized mice as a translational model to study the pharmacokinetics of statins}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {8}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057976}, pages = {1301 -- 1313}, year = {2014}, abstract = {Organic anion transporting polypeptide (Oatp) 1a/1b knockout and OATP1B1 and -1B3 humanized mouse models are promising tools for studying the roles of these transporters in drug disposition. Detailed characterization of these models will help to better understand their utility for predicting clinical outcomes. To advance this approach, we carried out a comprehensive analysis of these mouse lines by evaluating the compensatory changes in mRNA expression, quantifying the amounts of OATP1B1 and -1B3 protein by liquid chromatography-tandem mass spectrometry, and studying the active uptake in isolated hepatocytes and the pharmacokinetics of some prototypical substrates including statins. Major outcomes from these studies were 1) mostly moderate compensatory changes in only a few genes involved in drug metabolism and disposition, 2) a robust hepatic expression of OATP1B1 and -1B3 proteins in the respective humanized mouse models, and 3) functional activities of the human transporters in hepatocytes isolated from the humanized models with several substrates tested in vitro and with pravastatin in vivo. However, the expression of OATP1B1 and -1B3 in the humanized models did not significantly alter liver or plasma concentrations of rosuvastatin and pitavastatin compared with Oatp1a/1b knockout controls under the conditions used in our studies. Hence, although the humanized OATP1B1 and -1B3 mice showed in vitro and/or in vivo functional activity with some statins, further characterization of these models is required to define their potential use and limitations in the prediction of drug disposition and drug-drug interactions in humans.}, language = {en} } @article{ScheerMclaughlinRodeetal.2014, author = {Scheer, Nico and Mclaughlin, Lesley A. and Rode, Anja and MacLeod, Alastair Kenneth and Henderson, Colin J. and Wolf, Roland C.}, title = {Deletion of thirty murine cytochrome P450 genes results in viable mice with compromised drug metabolism}, series = {Drug Metabolism and Disposition}, volume = {42}, journal = {Drug Metabolism and Disposition}, number = {6}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-009X}, doi = {10.1124/dmd.114.057885}, pages = {1022 -- 1030}, year = {2014}, abstract = {In humans, 75\% of all drugs are metabolized by the cytochrome P450-dependent monooxygenase system. Enzymes encoded by the CYP2C, CYP2D, and CYP3A gene clusters account for ∼80\% of this activity. There are profound species differences in the multiplicity of cytochrome P450 enzymes, and the use of mouse models to predict pathways of drug metabolism is further complicated by overlapping substrate specificity between enzymes from different gene families. To establish the role of the hepatic and extrahepatic P450 system in drug and foreign chemical disposition, drug efficacy, and toxicity, we created a unique mouse model in which 30 cytochrome P450 genes from the Cyp2c, Cyp2d, and Cyp3a gene clusters have been deleted. Remarkably, despite a wide range of putative important endogenous functions, Cyp2c/2d/3a KO mice were viable and fertile, demonstrating that these genes have evolved primarily as detoxification enzymes. Although there was no overt phenotype, detailed examination showed Cyp2c/2d/3a KO mice had a smaller body size (15\%) and larger livers (20\%). Changes in hepatic morphology and a decreased blood glucose (30\%) were also noted. A five-drug cocktail of cytochrome P450 isozyme probe substrates were used to evaluate changes in drug pharmacokinetics; marked changes were observed in either the pharmacokinetics or metabolites formed from Cyp2c, Cyp2d, and Cyp3a substrates, whereas the metabolism of the Cyp1a substrate caffeine was unchanged. Thus, Cyp2c/2d/3a KO mice provide a powerful model to study the in vivo role of the P450 system in drug metabolism and efficacy, as well as in chemical toxicity.}, language = {en} } @article{ScheerWolf2014, author = {Scheer, Nico and Wolf, C. Roland}, title = {Genetically humanized mouse models of drug metabolizing enzymes and transporters and their applications}, series = {Xenobiotica}, volume = {44}, journal = {Xenobiotica}, number = {2}, publisher = {Taylor \& Francis}, address = {Abingdon}, issn = {1366-5928}, doi = {10.3109/00498254.2013.815831}, pages = {96 -- 108}, year = {2014}, abstract = {1. Drug metabolizing enzymes and transporters play important roles in the absorption, metabolism, tissue distribution and excretion of various compounds and their metabolites and thus can significantly affect their efficacy and safety. Furthermore, they can be involved in drug-drug interactions which can result in adverse responses, life-threatening toxicity or impaired efficacy. Significant species differences in the interaction of compounds with drug metabolizing enzymes and transporters have been described. 2. In order to overcome the limitation of animal models in accurately predicting human responses, a large variety of mouse models humanized for drug metabolizing enzymes and to a lesser extent drug transporters have been created. 3. This review summarizes the literature describing these mouse models and their key applications in studying the role of drug metabolizing enzymes and transporters in drug bioavailability, tissue distribution, clearance and drug-drug interactions as well as in human metabolite testing and risk assessment. 4. Though such humanized mouse models have certain limitations, there is great potential for their use in basic research and for testing and development of new medicines. These limitations and future potentials will be discussed.}, language = {en} } @article{HentschkeHagerHojdis2014, author = {Hentschke, Reinhard and Hager, Jonathan and Hojdis, Nils}, title = {Molecular Modeling Approach to the Prediction of Mechanical Properties of Silica-Reinforced Rubbers}, series = {Journal of Applied Polymer Science}, volume = {131}, journal = {Journal of Applied Polymer Science}, number = {18}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-4628}, doi = {10.1002/app.40806}, pages = {1 -- 9}, year = {2014}, abstract = {Recently, we have suggested a nanomechanical model for dissipative loss in filled elastomer networks in the context of the Payne effect. The mechanism is based on a total interfiller particle force exhibiting an intermittent loop, due to the combination of short-range repulsion and dispersion forces with a long-range elastic attraction. The sum of these forces leads, under external strain, to a spontaneous instability of "bonds" between the aggregates in a filler network and attendant energy dissipation. Here, we use molecular dynamics simulations to obtain chemically realistic forces between surface modified silica particles. The latter are combined with the above model to estimate the loss modulus and the low strain storage modulus in elastomers containing the aforementioned filler-compatibilizer systems. The model is compared to experimental dynamic moduli of silica filled rubbers. We find good agreement between the model predictions and the experiments as function of the compatibilizer's molecular structure and its bulk concentration.}, language = {en} } @article{SchroeterHoffmannVoigtetal.2014, author = {Schroeter, Rebecca and Hoffmann, Tamara and Voigt, Birgit and Meyer, Hanna and Bleisteiner, Monika and Muntel, Jan and J{\"u}rgen, Britta and Albrecht, Dirk and Becher, D{\"o}rte and Lalk, Michael and Evers, Stefan and Bongaerts, Johannes and Maurer, Karl-Heinz and Putzer, Harald and Hecker, Michael and Schweder, Thomas and Bremer, Erhard}, title = {Stress responses of the industrial workhorse Bacillus licheniformis to osmotic challenges}, series = {PLoS ONE}, volume = {8}, journal = {PLoS ONE}, number = {11}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0080956}, pages = {e80956}, year = {2014}, abstract = {The Gram-positive endospore-forming bacterium Bacillus licheniformis can be found widely in nature and it is exploited in industrial processes for the manufacturing of antibiotics, specialty chemicals, and enzymes. Both in its varied natural habitats and in industrial settings, B. licheniformis cells will be exposed to increases in the external osmolarity, conditions that trigger water efflux, impair turgor, cause the cessation of growth, and negatively affect the productivity of cell factories in biotechnological processes. We have taken here both systems-wide and targeted physiological approaches to unravel the core of the osmostress responses of B. licheniformis. Cells were suddenly subjected to an osmotic upshift of considerable magnitude (with 1 M NaCl), and their transcriptional profile was then recorded in a time-resolved fashion on a genome-wide scale. A bioinformatics cluster analysis was used to group the osmotically up-regulated genes into categories that are functionally associated with the synthesis and import of osmostress-relieving compounds (compatible solutes), the SigB-controlled general stress response, and genes whose functional annotation suggests that salt stress triggers secondary oxidative stress responses in B. licheniformis. The data set focusing on the transcriptional profile of B. licheniformis was enriched by proteomics aimed at identifying those proteins that were accumulated by the cells through increased biosynthesis in response to osmotic stress. Furthermore, these global approaches were augmented by a set of experiments that addressed the synthesis of the compatible solutes proline and glycine betaine and assessed the growth-enhancing effects of various osmoprotectants. Combined, our data provide a blueprint of the cellular adjustment processes of B. licheniformis to both sudden and sustained osmotic stress.}, language = {en} } @article{HandtkeSchroeterJuergenetal.2014, author = {Handtke, Stefan and Schroeter, Rebecca and J{\"u}rgen, Britta and Methling, Karen and Schl{\"u}ter, Rabea and Albrecht, Dirk and Hijum, Sacha A. F. T. van and Bongaerts, Johannes and Maurer, Karl-Heinz and Lalk, Michael and Schweder, Thomas and Hecker, Michael and Voigt, Birgit}, title = {Bacillus pumilus reveals a remarkably high resistance to hydrogen peroxide provoked oxidative stress}, series = {PLOS one}, volume = {9}, journal = {PLOS one}, number = {1}, publisher = {PLOS}, address = {San Francisco}, issn = {1932-6203}, doi = {10.1371/journal.pone.0085625}, pages = {e85625}, year = {2014}, abstract = {Bacillus pumilus is characterized by a higher oxidative stress resistance than other comparable industrially relevant Bacilli such as B. subtilis or B. licheniformis. In this study the response of B. pumilus to oxidative stress was investigated during a treatment with high concentrations of hydrogen peroxide at the proteome, transcriptome and metabolome level. Genes/proteins belonging to regulons, which are known to have important functions in the oxidative stress response of other organisms, were found to be upregulated, such as the Fur, Spx, SOS or CtsR regulon. Strikingly, parts of the fundamental PerR regulon responding to peroxide stress in B. subtilis are not encoded in the B. pumilus genome. Thus, B. pumilus misses the catalase KatA, the DNA-protection protein MrgA or the alkyl hydroperoxide reductase AhpCF. Data of this study suggests that the catalase KatX2 takes over the function of the missing KatA in the oxidative stress response of B. pumilus. The genome-wide expression analysis revealed an induction of bacillithiol (Cys-GlcN-malate, BSH) relevant genes. An analysis of the intracellular metabolites detected high intracellular levels of this protective metabolite, which indicates the importance of bacillithiol in the peroxide stress resistance of B. pumilus.}, language = {en} } @incollection{FrotscherGossmannRaatschenetal.2015, author = {Frotscher, Ralf and Goßmann, Matthias and Raatschen, Hans-J{\"u}rgen and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM}, series = {Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45)}, booktitle = {Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45)}, publisher = {Springer}, address = {Heidelberg}, isbn = {978-3-319-02534-6 ; 978-3-319-02535-3}, pages = {187 -- 212}, year = {2015}, abstract = {We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments.}, language = {en} } @article{SeifarthGossmannGrosseetal.2015, author = {Seifarth, Volker and Goßmann, Matthias and Grosse, J. O. and Becker, C. and Heschel, I. and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds}, series = {Urologia Internationalis}, volume = {2015}, journal = {Urologia Internationalis}, number = {95}, publisher = {Karger}, address = {Basel}, issn = {0042-1138}, doi = {10.1159/000368419}, pages = {106 -- 113}, year = {2015}, language = {en} } @article{PilasIkenSelmeretal.2015, author = {Pilas, Johanna and Iken, Heiko and Selmer, Thorsten and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Development of a multi-parameter sensor chip for the simultaneous detection of organic compounds in biogas processes}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431894}, pages = {1306 -- 1312}, year = {2015}, abstract = {An enzyme-based multi-parameter biosensor is developed for monitoring the concentration of formate, d-lactate, and l-lactate in biological samples. The sensor is based on the specific dehydrogenation by an oxidized β-nicotinamide adenine dinucleotide (NAD+)-dependent dehydrogenase (formate dehydrogenase, d-lactic dehydrogenase, and l-lactic dehydrogenase, respectively) in combination with a diaphorase from Clostridium kluyveri (EC 1.8.1.4). The enzymes are immobilized on a platinum working electrode by cross-linking with glutaraldehyde (GA). The principle of the determination scheme in case of l-lactate is as follows: l-lactic dehydrogenase (l-LDH) converts l-lactate into pyruvate by reaction with NAD+. In the presence of hexacyanoferrate(III), the resulting reduced β-nicotinamide adenine dinucleotide (NADH) is then regenerated enzymatically by diaphorase. The electrochemical detection is based on the current generated by oxidation of hexacyanoferrate(II) at an applied potential of +0.3 V vs. an Ag/AgCl reference electrode. The biosensor will be electrochemically characterized in terms of linear working range and sensitivity. Additionally, the successful practical application of the sensor is demonstrated in an extract from maize silage.}, language = {en} } @article{BreuerRaueKirschbaumetal.2015, author = {Breuer, Lars and Raue, Markus and Kirschbaum, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Light-controllable polymeric material based on temperature-sensitive hydrogels with incorporated graphene oxide}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201431944}, pages = {1368 -- 1374}, year = {2015}, abstract = {Poly(N-isopropylacrylamide) (PNIPAAm) hydrogel films with incorporated graphene oxide (GO) were developed and tested as light-stimulated actuators. GO dispersions were synthesized via Hummers method and characterized toward their optical properties and photothermal energy conversion. The hydrogels were prepared by means of photopolymerization. In addition, the influence of GO within the hydrogel network on the lower critical solution temperature (LCST) was investigated by differential scanning calorimetry (DSC). The optical absorbance and the response to illumination were determined as a function of GO concentration for thin hydrogel films. A proof of principle for the stimulation with light was performed.}, language = {en} } @article{SchiffelsSelmer2015, author = {Schiffels, Johannes and Selmer, Thorsten}, title = {A flexible toolbox to study protein-assisted metalloenzyme assembly in vitro}, series = {Biotechnology and Bioengineering}, volume = {112}, journal = {Biotechnology and Bioengineering}, number = {11}, publisher = {Wiley}, address = {Weinheim}, issn = {1097-0290}, doi = {10.1002/bit.25658}, pages = {2360 -- 2372}, year = {2015}, language = {en} } @article{VoigtAlbrechtSieversetal.2015, author = {Voigt, Birgit and Albrecht, Dirk and Sievers, Susanne and Becher, D{\"o}rte and Bongaerts, Johannes and Evers, Stefan and Schweder, Thomas and Maurer, Karl-Heinz and Hecker, Michael}, title = {High-resolution proteome maps of Bacillus licheniformis cells growing in minimal medium}, series = {Proteomics}, volume = {15}, journal = {Proteomics}, number = {15}, publisher = {Wiley}, address = {Weinheim}, issn = {1615-9861}, doi = {10.1002/pmic.201400504}, pages = {2629 -- 2633}, year = {2015}, language = {en} } @article{MolinnusBaeckerSiegertetal.2015, author = {Molinnus, Denise and B{\"a}cker, Matthias and Siegert, Petra and Willenberg, H. and Poghossian, Arshak and Keusgen, M. and Sch{\"o}ning, Michael Josef}, title = {Detection of Adrenaline Based on Substrate Recycling Amplification}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.708}, pages = {540 -- 543}, year = {2015}, abstract = {An amperometric enzyme biosensor has been applied for the detection of adrenaline. The adrenaline biosensor has been prepared by modification of an oxygen electrode with the enzyme laccase that operates at a broad pH range between pH 3.5 to pH 8. The enzyme molecules were immobilized via cross-linking with glutaraldehyde. The sensitivity of the developed adrenaline biosensor in different pH buffer solutions has been studied.}, language = {en} } @article{PilasMarianoKeusgenetal.2015, author = {Pilas, Johanna and Mariano, K. and Keusgen, M. and Selmer, Thorsten and Sch{\"o}ning, Michael Josef}, title = {Optimization of an Enzyme-based Multi-parameter Biosensor for Monitoring Biogas Processes}, series = {Procedia Engineering}, volume = {120}, journal = {Procedia Engineering}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1877-7058}, doi = {10.1016/j.proeng.2015.08.702}, pages = {532 -- 535}, year = {2015}, language = {en} } @article{TakenagaSchneiderErbayetal.2015, author = {Takenaga, Shoko and Schneider, Benno and Erbay, E. and Biselli, Manfred and Schnitzler, Thomas and Sch{\"o}ning, Michael Josef and Wagner, Torsten}, title = {Fabrication of biocompatible lab-on-chip devices for biomedical applications by means of a 3D-printing process}, series = {Physica status solidi (a)}, volume = {212}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201532053}, pages = {1347 -- 1352}, year = {2015}, abstract = {A new microfluidic assembly method for semiconductor-based biosensors using 3D-printing technologies was proposed for a rapid and cost-efficient design of new sensor systems. The microfluidic unit is designed and printed by a 3D-printer in just a few hours and assembled on a light-addressable potentiometric sensor (LAPS) chip using a photo resin. The cell growth curves obtained from culturing cells within microfluidics-based LAPS systems were compared with cell growth curves in cell culture flasks to examine biocompatibility of the 3D-printed chips. Furthermore, an optimal cell culturing within microfluidics-based LAPS chips was achieved by adjusting the fetal calf serum concentrations of the cell culture medium, an important factor for the cell proliferation.}, language = {en} } @incollection{SrivastavaKnolleHoyleretal.2015, author = {Srivastava, Alok and Knolle, Friedhart and Hoyler, Friedrich and Scherer, Ulrich W. and Schnug, Ewald}, title = {Uranium Toxicity in the State of Punjab in North-Western India}, series = {Management of Natural Resources in a Changing Environment}, booktitle = {Management of Natural Resources in a Changing Environment}, publisher = {Springer}, address = {Cham}, isbn = {978-3-319-12559-6}, doi = {10.1007/978-3-319-12559-6_21}, pages = {271 -- 275}, year = {2015}, abstract = {Lately there has been an increasing concern about uranium toxicity in some districts of Punjab State located in the North Western part of India after the publication of a report (Blaurock-Busch et al. 2010) which showed that the concentration of uranium in hair and urine of children suffering from physical deformities, neurological and mental disorder from Malwa region (Fig. 1) of Punjab State was manifold higher than the reference ranges. A train which connects the affected region with the nearby city of Bikaner which has a Cancer Hospital has been nicknamed as Cancer Express due to the frenzy generated on account of uranium related toxicity.}, language = {en} } @article{CehreliAkpinarTemizArtmannetal.2015, author = {Cehreli, Ruksan and Akpinar, Hale and Temiz Artmann, Ayseg{\"u}l and Sagol, Ozgul}, title = {Effects of Glutamine and Omega-3 Fatty Acids on Erythrocyte Deformability and Oxidative Damage in Rat Model of Enterocolitis}, series = {Gastroenterology Research}, volume = {8}, journal = {Gastroenterology Research}, number = {5}, issn = {1918-2813}, doi = {10.14740/gr683w}, pages = {265 -- 273}, year = {2015}, language = {en} } @inproceedings{BreuerRaueMangetal.2015, author = {Breuer, Lars and Raue, Markus and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, Ronald and Wagner, Torsten}, title = {Light-stimulated hydrogel actuators with incorporated graphene oxide for microfluidic applications}, series = {12. Dresdner Sensor-Symposium 2015}, booktitle = {12. Dresdner Sensor-Symposium 2015}, doi = {10.5162/12dss2015/P5.8}, pages = {206 -- 209}, year = {2015}, language = {en} } @article{AlKaidyDuweHusteretal.2015, author = {Al-Kaidy, Huschyar and Duwe, Anna and Huster, Manuel and Muffler, Kai and Schlegel, Christin and Tim, Sieker and Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Biotechnology and bioprocess engineering - from the first ullmann's article to recent trends}, series = {ChemBioEng Reviews}, volume = {2}, journal = {ChemBioEng Reviews}, number = {3}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/cben.201500008}, pages = {175 -- 184}, year = {2015}, abstract = {For several thousand years, biotechnology and its associated technical processes have had a great impact on the development of mankind. Based on empirical methods, in particular for the production of foodstuffs and daily commodities, these disciplines have become one of the most innovative future issues. Due to the increasing detailed understanding of cellular processes, production strains can now be optimized. In combination with modern bioprocesses, a variety of bulk and fine chemicals as well as pharmaceuticals can be produced efficiently. In this article, some of the current trends in biotechnology are discussed.}, language = {en} } @article{ThielMufflerTippkoetteretal.2015, author = {Thiel, Alexander and Muffler, Kai and Tippk{\"o}tter, Nils and Suck, Kirstin and Sohling, Ulrich and Hruschka, Steffen M. and Ulber, Roland}, title = {A novel integrated downstream processing approach to recover sinapic acid, phytic acid and proteins from rapeseed meal}, series = {Journal of Chemical Technology and Biotechnology}, volume = {90}, journal = {Journal of Chemical Technology and Biotechnology}, number = {11}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/jctb.4664}, pages = {1999 -- 2006}, year = {2015}, abstract = {BACKGROUND Currently, several techniques exist for the downstream processing of protein, phytic acid and sinapic acid from rapeseed and rapeseed meal, but no technique has been developed to separate all of the components in one process. In this work, two new downstream processing strategies focusing on recovering sinapic acid, phytic acid and protein from rapeseed meal were established. RESULTS The sinapic acid content was enhanced by a factor of 4.5 with one method and 5.1 with the other. The isolation of sinapic acid was accomplished using a zeolite-based adsorbent with high adsorptive and optimal desorption characteristics. Phytic acid was isolated using the anion-exchange resin Purolite A200®. In addition, the processes resulted in two separated protein fractions. The ratios of globulin and albumin ratio to the total protein were 59.2\% and 40.1\%, respectively. The steps were then combined in two different ways: (a) a 'sequential process' using the zeolite and A200 in batch processes; and (b) a 'parallel process' using only A200 in a chromatographic system to separate all of the compounds. CONCLUSIONS It can be concluded that isolation of all three components was possible in both processes. These could enhance the added value of current processes using rapeseed meal as a protein source. © 2015 Society of Chemical Industry}, language = {en} } @article{WiesenTippkoetterMuffleretal.2015, author = {Wiesen, Sebastian and Tippk{\"o}tter, Nils and Muffler, Kai and Suck, Kirstin and Sohling, Ulrich and Ruf, Friedrich and Ulber, Roland}, title = {Adsorption of fatty acids to layered double hydroxides in aqueous systems}, series = {Adsorption}, volume = {21}, journal = {Adsorption}, number = {6-7}, publisher = {Springer}, address = {Berlin}, pages = {459 -- 466}, year = {2015}, abstract = {Due to their anion exchange characteristics, layered double hydroxides (LDHs) are suitable for the detoxification of aqueous, fatty acid containing fermentation substrates. The aim of this study is to examine the adsorption mechanism, using crude glycerol from plant oil esterification as a model system. Changes in the intercalation structure in relation to the amount of fatty acids adsorbed are monitored by X-ray diffraction and infra-red spectroscopy. Additionally, calcination of LDH is investigated in order to increase the binding capacity for fatty acids. Our data propose that, at ambient temperature, fatty acids can be bound to the hydrotalcite by adsorption or in addition by intercalation, depending on fatty acid concentration. The adsorption of fatty acids from crude glycerol shows a BET-like behavior. Above a fatty acid concentration of 3.5 g L-1, intercalation of fatty acids can be shown by the appearance of an increased interlayer spacing. This observation suggests a two phase adsorption process. Calcination of LDHs allows increasing the binding capacity for fatty acids by more than six times, mainly by reduction of structural CO32-.}, language = {en} } @article{PaulssenHoehrHouetal.2015, author = {Paulßen, Elisabeth and Hoehr, Cornelia and Hou, Xinchi and Hanemaayer, Victoire and Zeisler, Stefan and Adam, Michael J. and Ruth, Thomas J. and Celler, Anna and Buckley, Ken and Benard, Francois and Schaffer, Paul}, title = {Production of Y-86 and other radiometals for research purposes using a solution target system}, series = {Nuclear medicine and biology}, volume = {42}, journal = {Nuclear medicine and biology}, number = {11}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9614}, doi = {10.1016/j.nucmedbio.2015.06.005}, pages = {842 -- 849}, year = {2015}, language = {en} } @article{ScheerKapelyukhRodeetal.2015, author = {Scheer, Nico and Kapelyukh, Yury and Rode, Anja and Oswald, Stefan and Busch, Diana and Mclaughlin, Lesley A. and Lin, De and Henderson, Colin J. and Wolf, C. Roland}, title = {Defining Human Pathways of Drug Metabolism In Vivo through the Development of a Multiple Humanized Mouse Model}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {11}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-009x}, doi = {10.1124/dmd.115.065656}, pages = {1679 -- 1690}, year = {2015}, language = {en} } @article{HoughNalwalkDingetal.2015, author = {Hough, Lindsay B. and Nalwalk, Julia W. and Ding, Xinxin and Scheer, Nico}, title = {Opioid Analgesia in P450 Gene Cluster Knockout Mice: A Search for Analgesia-Relevant Isoforms}, series = {Drug Metabolism and Disposition}, volume = {43}, journal = {Drug Metabolism and Disposition}, number = {9}, issn = {1521-009x}, doi = {10.1124/dmd.115.065490}, pages = {1326 -- 1330}, year = {2015}, language = {en} } @article{HendersonMclaughlinScheeretal.2015, author = {Henderson, Colin J. and Mclaughlin, Lesley A. and Scheer, Nico and Stanley, Lesley A. and Wolf, C. Roland}, title = {Cytochrome b5 Is a Major Determinant of Human Cytochrome P450 CYP2D6 and CYP3A4 Activity In Vivo s}, series = {Molecular Pharmacology}, volume = {87}, journal = {Molecular Pharmacology}, number = {4}, publisher = {ASPET}, address = {Bethesda}, issn = {1521-0111}, doi = {10.1124/mol.114.097394}, pages = {733 -- 739}, year = {2015}, language = {en} } @incollection{WolfKapelyukhScheeretal.2015, author = {Wolf, C. Roland and Kapelyukh, Yury and Scheer, Nico and Henderson, Colin J.}, title = {Application of Humanised and Other Transgenic Models to Predict Human Responses to Drugs}, editor = {Wilson, Alan G. E.}, publisher = {RSC Publ.}, address = {Cambridge}, isbn = {978-1-78262-778-4}, doi = {10.1039/9781782622376-00152}, pages = {152 -- 176}, year = {2015}, abstract = {The use of transgenic animal models has transformed our knowledge of complex biochemical pathways in vivo. It has allowed disease processes to be modelled and used in the development of new disease prevention and treatment strategies. They can also be used to define cell- and tissue-specific pathways of gene regulation. A further major application is in the area of preclinical development where such models can be used to define pathways of chemical toxicity, and the pathways that regulate drug disposition. One major application of this approach is the humanisation of mice for the proteins that control drug metabolism and disposition. Such models can have numerous applications in the development of drugs and in their more sophisticated use in the clinic.}, language = {en} } @article{HagerHentschkeHojdisetal.2015, author = {Hager, Jonathan and Hentschke, Reinhard and Hojdis, Nils and Karimi-Varzaneh, Hossein Ali}, title = {Computer Simulation of Particle-Particle Interaction in a Model Polymer Nanocomposite}, series = {Macromolecules}, volume = {48}, journal = {Macromolecules}, number = {24}, issn = {1520-5835}, doi = {10.1021/acs.macromol.5b01864}, pages = {9039 -- 9049}, year = {2015}, language = {en} } @misc{StadtmuellerTippkoetterUlber2015, author = {Stadtm{\"u}ller, Ralf and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Method for production of single-stranded macronucleotides}, year = {2015}, abstract = {The invention relates to a method for production of single-stranded macronucleotides by amplifying and ligating an extended monomeric single-stranded target nucleic acid sequence (targetss) into a repetitive cluster of double-stranded target nucleic acid sequences (targetds), and subsequently cloning the construct into a vector (aptagene vector). The aptagene vector is transformed into host cells for replication of the aptagene and isolated in order to optain single-stranded target sequences (targetss). The invention also relates to single-stranded nucleic acids, produced by a method of the invention.}, language = {en} } @article{BreuerRaueStrobeletal.2016, author = {Breuer, Lars and Raue, Markus and Strobel, M. and Mang, Thomas and Sch{\"o}ning, Michael Josef and Thoelen, R. and Wagner, Torsten}, title = {Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems}, series = {Physica status solidi (a)}, volume = {213}, journal = {Physica status solidi (a)}, number = {6}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6300}, doi = {10.1002/pssa.201533056}, pages = {1520 -- 1525}, year = {2016}, abstract = {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.}, language = {en} } @inproceedings{KasperSchiffelsKrafftetal.2016, author = {Kasper, Katharina and Schiffels, Johannes and Krafft, Simone and Kuperjans, Isabel and Elbers, Gereon and Selmer, Thorsten}, title = {Biogas Production on Demand Regulated by Butyric Acid Addition}, series = {IOP Conference Series: Earth and Environmental Science. Bd. 32}, volume = {32}, booktitle = {IOP Conference Series: Earth and Environmental Science. Bd. 32}, issn = {1755-1315}, doi = {10.1088/1755-1315/32/1/012009}, pages = {012009/1 -- 012009/4}, year = {2016}, language = {en} } @article{NiedermeyerZhouDursunetal.2016, author = {Niedermeyer, Angela and Zhou, Bei and Dursun, G{\"o}zde and Temiz Artmann, Ayseg{\"u}l and Markert, Bernd}, title = {An examination of tissue engineered scaffolds in a bioreactor}, series = {Proceedings in Applied Mathematics and Mechanics PAMM}, volume = {16}, journal = {Proceedings in Applied Mathematics and Mechanics PAMM}, number = {1}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1617-7061}, doi = {10.1002/pamm.201610038}, pages = {99 -- 100}, year = {2016}, abstract = {Replacement tissues, designed to fill in articular cartilage defects, should exhibit the same properties as the native material. The aim of this study is to foster the understanding of, firstly, the mechanical behavior of the material itself and, secondly, the influence of cultivation parameters on cell seeded implants as well as on cell migration into acellular implants. In this study, acellular cartilage replacement material is theoretically, numerically and experimentally investigated regarding its viscoelastic properties, where a phenomenological model for practical applications is developed. Furthermore, remodeling and cell migration are investigated.}, language = {en} } @article{HeinzeMangPopescuetal.2016, author = {Heinze, D. and Mang, Thomas and Popescu, C. and Weichold, O.}, title = {Effect of side chain length and degree of polymerization on the decomposition and crystallization behaviour of chlorinated poly(vinyl ester) oligomers}, series = {Thermochimica Acta}, volume = {637}, journal = {Thermochimica Acta}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0040-6031 (electronic)}, doi = {10.1016/j.tca.2016.05.015}, pages = {143 -- 153}, year = {2016}, abstract = {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.}, language = {en} } @article{MolinnusSorichBartzetal.2016, author = {Molinnus, Denise and Sorich, Maren and Bartz, Alexander and Siegert, Petra and Willenberg, Holger S. and Lisdat, Fred and Poghossian, Arshak and Keusgen, Michael and Sch{\"o}ning, Michael Josef}, title = {Towards an adrenaline biosensor based on substrate recycling amplification in combination with an enzyme logic gate}, series = {Sensors and Actuators B: Chemical}, volume = {237}, journal = {Sensors and Actuators B: Chemical}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0925-4005}, doi = {10.1016/j.snb.2016.06.064}, pages = {190 -- 195}, year = {2016}, abstract = {An amperometric biosensor using a substrate recycling principle was realized for the detection of low adrenaline concentrations (1 nM) by measurements in phosphate buffer and Ringer's solution at pH 6.5 and pH 7.4, respectively. In proof-of-concept experiments, a Boolean logic-gate principle has been applied to develop a digital adrenaline biosensor based on an enzyme AND logic gate. The obtained results demonstrate that the developed digital biosensor is capable for a rapid qualitative determination of the presence/absence of adrenaline in a YES/NO statement. Such digital biosensor could be used in clinical diagnostics for the control of a correct insertion of a catheter in the adrenal veins during adrenal venous-sampling procedure.}, language = {en} } @article{GhoschBaierSchuetzetal.2016, author = {Ghosch, S. and Baier, M. and Sch{\"u}tz, J. and Schneider, Felix and Scherer, Ulrich W.}, title = {Analysis of electronic autoradiographs by mathematical post-processing}, series = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, volume = {171}, journal = {Radiation Effects and Defects in Solids: Incorporating plasma science and plasma technology}, number = {1-2}, publisher = {Taylor \& Francis}, address = {London}, issn = {1029-4953}, doi = {10.1080/10420150.2016.1155587}, pages = {161 -- 172}, year = {2016}, abstract = {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.}, language = {en} } @article{RoeschKratzHeringetal.2016, author = {R{\"o}sch, C. and Kratz, F. and Hering, T. and Trautmann, S. and Umanskaya, N. and Tippk{\"o}tter, Nils and M{\"u}ller-Renno, C.M. and Ulber, R. and Hannig, M. and Ziegler, C.}, title = {Albumin-lysozyme interactions: cooperative adsorption on titanium and enzymatic activity}, series = {Colloids and Surfaces B: Biointerfaces}, volume = {149}, journal = {Colloids and Surfaces B: Biointerfaces}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.colsurfb.2016.09.048}, pages = {115 -- 121}, year = {2016}, abstract = {The interplay of albumin (BSA) and lysozyme (LYZ) adsorbed simultaneously on titanium was analyzed by gel electrophoresis and BCA assay. It was found that BSA and lysozyme adsorb cooperatively. Additionally, the isoelectric point of the respective protein influences the adsorption. Also, the enzymatic activity of lysozyme and amylase (AMY) in mixtures with BSA was considered with respect to a possible influence of protein-protein interaction on enzyme activity. Indeed, an increase of lysozyme activity in the presence of BSA could be observed. In contrast, BSA does not influence the activity of amylase.}, language = {en} } @article{RothTippkoetter2016, author = {Roth, Jasmine and Tippk{\"o}tter, Nils}, title = {Evaluation of lignocellulosic material for butanol production using enzymatic hydrolysate medium}, series = {Cellulose Chemistry and Technology}, volume = {50}, journal = {Cellulose Chemistry and Technology}, number = {3-4}, publisher = {Editura Academiei Romane}, address = {Bukarest}, pages = {405 -- 410}, year = {2016}, abstract = {Butanol is a promising gasoline additive and platform chemical that can be readily produced via acetone-butanolethanol (ABE) fermentation from pretreated lignocellulosic materials. This article examines lignocellulosic material from beech wood for ABE fermentation, using Clostridium acetobutylicum. First, the utilization of both C₅₋ (xylose) and C₆₋ (glucose) sugars as sole carbon source was investigated in static cultivation, using serum bottles and synthetic medium. The utilization of pentose sugar resulted in a solvent yield of 0.231 g·g_sugar⁻¹, compared to 0.262 g·g_sugar⁻¹ using hexose. Then, the Organosolv pretreated crude cellulose fibers (CF) were enzymatically decomposed, and the resulting hydrolysate medium was analyzed for inhibiting compounds (furans, organic acids, phenolics) and treated with ionexchangers for detoxification. Batch fermentation in a bioreactor using CF hydrolysate medium resulted in a total solvent yield of 0.20 gABE·g_sugar⁻¹.}, language = {en} } @article{AlKaidyTippkoetter2016, author = {Al-Kaidy, Huschyar and Tippk{\"o}tter, Nils}, title = {Superparamagnetic hydrophobic particles as shell material for digital microfluidic droplets and proof-of-principle reaction assessments with immobilized laccase}, series = {Engineering in Life Sciences}, volume = {16}, journal = {Engineering in Life Sciences}, number = {3}, publisher = {Wiley-VCH}, address = {Weinheim}, doi = {10.1002/elsc.201400124}, pages = {222 -- 230}, year = {2016}, abstract = {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.}, language = {en} } @article{AlKaidyKuthanHeringetal.2016, author = {Al-Kaidy, Huschyar and Kuthan, Kai and Hering, Thomas and Tippk{\"o}tter, Nils}, title = {Aqueous droplets used as enzymatic microreactors and their electromagnetic actuation}, series = {Journal of Visualized Experiments}, journal = {Journal of Visualized Experiments}, number = {Issue 126}, issn = {1940-087X}, doi = {10.3791/54643}, year = {2016}, abstract = {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.}, language = {en} } @article{WulfhorstDuweMerseburgetal.2016, author = {Wulfhorst, Helene and Duwe, Anna-Maria and Merseburg, Johannes and Tippk{\"o}tter, Nils}, title = {Compositional analysis of pretreated (beech) wood using differential scanning calorimetry and multivariate data analysis}, series = {Tetrahedron}, volume = {72}, journal = {Tetrahedron}, number = {46}, publisher = {Elsevier}, address = {Amsterdam}, doi = {10.1016/j.tet.2016.04.029}, pages = {7329 -- 7334}, year = {2016}, abstract = {The composition of plant biomass varies depending on the feedstock and pre-treatment conditions and influences its processing in biorefineries. In order to ensure optimal process conditions, the quantitative proportion of the main polymeric components of the pre-treated biomass has to be determined. Current standard procedures for biomass compositional analysis are complex, the measurements are afflicted with errors and therefore often not comparable. Hence, new powerful analytical methods are urgently required to characterize biomass. In this contribution, Differential Scanning Calorimetry (DSC) was applied in combination with multivariate data analysis (MVA) to detect the cellulose content of the plant biomass pretreated by Liquid Hot Water (LHW) and Organosolv processes under various conditions. Unlike conventional techniques, the developed analytic method enables the accurate quantification of monosaccharide content of the plant biomass without any previous sample preparation. It is easy to handle and avoids errors in sample preparation.}, language = {en} } @inproceedings{EngelThieringerTippkoetter2016, author = {Engel, M. and Thieringer, J. and Tippk{\"o}tter, Nils}, title = {Microbial electrosynthesis for sustainable biobutanol production}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {77 -- 78}, year = {2016}, language = {en} } @inproceedings{HeringUlberTippkoetter2016, author = {Hering, T. and Ulber, Roland and Tippk{\"o}tter, Nils}, title = {Development of a screening system for antimicrobial surfaces}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {129}, year = {2016}, language = {en} } @inproceedings{RothMoehringTippkoetter2016, author = {Roth, J. and M{\"o}hring, S. and Tippk{\"o}tter, Nils}, title = {Characterization and evaluation of lignocellulosic biomass 130 hydrolysates for ABE fermentation}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {130}, year = {2016}, language = {en} } @inproceedings{MoehringWulfhorstRothetal.2016, author = {M{\"o}hring, S. and Wulfhorst, H. and Roth, J. and Tippk{\"o}tter, Nils}, title = {Pretreatment strategies for lignocellulosic biomass}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {131}, year = {2016}, language = {en} } @inproceedings{CapitainHeringTippkoetteretal.2016, author = {Capitain, C. and Hering, T. and Tippk{\"o}tter, Nils and Ulber, R.}, title = {Enzymatic polymerization of lignin model compounds and solubilized lignin in an aqueous ethanol extract}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {151 -- 152}, year = {2016}, language = {en} } @inproceedings{WulfhorstDuweMoehringetal.2016, author = {Wulfhorst, H. and Duwe, A. and M{\"o}hring, S. and Jurca, O. and Tippk{\"o}tter, Nils}, title = {Analysis of pretreated biomass by differential scanning 132 calorimetry and multivariate data analysis}, series = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, booktitle = {New frontiers of biotech-processes (Himmelfahrtstagung) : 02-04 May 2016, Rhein-Mosel-Halle, Koblenz/Germany}, publisher = {DECHEMA}, address = {Frankfurt am Main}, pages = {132}, year = {2016}, language = {en} } @article{PaulssenLengkeekLeetal.2016, author = {Paulßen, Elisabeth and Lengkeek, Nigel A. and Le, Van So and Pellegrini, Paul A. and Greguric, Ivan and Weiner, Ron}, title = {The role of additives in moderating the influence of Fe(III) and Cu(II) on the radiochemical yield of [⁶⁸Ga(DOTATATE)]}, series = {Applied Radiation and Isotopes}, volume = {107}, journal = {Applied Radiation and Isotopes}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9800}, doi = {10.1016/j.apradiso.2015.09.008}, pages = {13 -- 16}, year = {2016}, abstract = {[⁶⁸Ga(DOTATATE)] has demonstrated its clinical usefulness. Both Fe³⁺ and Cu²⁺, potential contaminants in Gallium-68 generator eluent, substantially reduce the radiochemical (RC) yield of [⁶⁸Ga(DOTATATE)] if the metal/ligand ratio of 1:1 is exceeded. A variety of compounds were examined for their potential ability to reduce this effect. Most had no effect on RC yield. However, addition of phosphate diminished the influence of Fe³⁺ by likely forming an insoluble iron salt. Addition of ascorbic acid reduced Cu²⁺ and Fe³⁺ to Cu⁺ and Fe²⁺ respectively, both of which have limited impact on RC yields. At low ligand amounts (5 nmol DOTATATE), the addition of 30 nmol phosphate (0.19 mM) increased the tolerance of Fe3⁺ from 4 nmol to 10 nmol (0.06 mM), while the addition of ascorbic acid allowed high RC yields (>95\%) in the presence of 40 nmol Fe³⁺ (0.25 mM) and 100 nmol Cu²⁺ (0.63 mM). The effect of ascorbic acid was highly pH-dependant, and gave optimal results at pH 3.}, language = {en} } @article{InfantinoPaulssenMostaccietal.2016, author = {Infantino, Angelo and Paulßen, Elisabeth and Mostacci, Domiziano and Schaffer, Paul and Trinczek, Michael and Hoehr, Cornelia}, title = {Assessment of the production of medical isotopes using the Monte Carlo code FLUKA: Simulations against experimental measurements}, series = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms}, volume = {366}, journal = {Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1872-9584}, doi = {10.1016/j.nimb.2015.10.067}, pages = {117 -- 123}, year = {2016}, abstract = {The Monte Carlo code FLUKA is used to simulate the production of a number of positron emitting radionuclides, ¹⁸F, ¹³N, ⁹⁴Tc, ⁴⁴Sc, ⁶⁸Ga, ⁸⁶Y, ⁸⁹Zr, ⁵²Mn, ⁶¹Cu and ⁵⁵Co, on a small medical cyclotron with a proton beam energy of 13 MeV. Experimental data collected at the TR13 cyclotron at TRIUMF agree within a factor of 0.6 ± 0.4 with the directly simulated data, except for the production of ⁵⁵Co, where the simulation underestimates the experiment by a factor of 3.4 ± 0.4. The experimental data also agree within a factor of 0.8 ± 0.6 with the convolution of simulated proton fluence and cross sections from literature. Overall, this confirms the applicability of FLUKA to simulate radionuclide production at 13 MeV proton beam energy.}, language = {en} } @article{ZhangHeimbachScheeretal.2016, author = {Zhang, Jin and Heimbach, Tycho and Scheer, Nico and Barve, Avantika and Li, Wenkui and Lin, Wen and He, Handan}, title = {Clinical Exposure Boost Predictions by Integrating Cytochrome P450 3A4-Humanized Mouse Studies With PBPK Modeling}, series = {Journal of Pharmaceutical Sciences}, volume = {Volume 105}, journal = {Journal of Pharmaceutical Sciences}, number = {Issue 4}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0022-3549}, doi = {doi.org/10.1016/j.xphs.2016.01.021}, pages = {1398 -- 1404}, year = {2016}, abstract = {NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.}, language = {en} }