@article{UlberPothMonzonetal.2010, author = {Ulber, Roland and Poth, Sebastian and Monzon, Magaly and Tippk{\"o}tter, Nils}, title = {Prozessintegration von Hydrolyse und Fermentation von Cellulose- Faserstoff}, series = {Chemie Ingenieur Technik}, volume = {82}, journal = {Chemie Ingenieur Technik}, number = {1-2}, issn = {1522-2640}, doi = {10.1002/cite.200900103}, pages = {135 -- 139}, year = {2010}, abstract = {Ein viel versprechender erneuerbarer Rohstoff f{\"u}r die Produktion von Chemikalien und Treibstoffen ist Lignocellulose aus pflanzlicher Biomasse. Die darin enthaltenen Zucker k{\"o}nnen mittels enzymatischer Hydrolyse freigesetzt und fermentativ zu Ethanol umgesetzt werden. Ein interessanter Ansatz ist dabei die simultane Verzuckerung und Fermentation. Hefen und Enzyme haben mit 30 °C bzw. 50 °C zwar unterschiedliche Temperaturoptima, es konnte aber gezeigt werden, dass auch bei den niedrigeren Temperaturen eine Umsetzung der Cellulose zu Glucose erfolgt, wenn auch langsamer als bei optimalen Bedingungen. Außerdem konnte in Vorversuchen gezeigt werden, dass Ethanol in den zu erwartenden Konzentrationen keinen Einfluss auf die enzymatische Umsetzung hat.}, language = {de} } @article{SiekerNeunerDimitrovaetal.2010, author = {Sieker, Tim and Neuner, Andreas and Dimitrova, Darina and Tippk{\"o}tter, Nils and Bart, Hans-J{\"o}rg and Heinzle, Elmar and Ulber, Roland}, title = {Grassilage als Rohstoff f{\"u}r die chemische Industrie}, series = {Chemie Ingenieur Technik}, volume = {82}, journal = {Chemie Ingenieur Technik}, number = {8, Special Issue: Industrielle Nutzung nachwachsender Rohstoffe}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1522-2640}, doi = {10.1002/cite.201000088}, pages = {1153 -- 1159}, year = {2010}, abstract = {Grassilage stellt einen nachwachsenden Rohstoff mit großem Potenzial dar. Neben Cellulose und Hemicellulose enth{\"a}lt sie auch organische S{\"a}uren, insbesondere Milchs{\"a}ure. In einem Bioraffinerie-Projekt wird die Milchs{\"a}ure aus der Silage isoliert und mit gentechnisch optimierten St{\"a}mmen zu L-Lysin weiterverarbeitet. Die Lignocellulose wird hydrolysiert und zu Ethanol fermentiert. Ein besonderes Augenmerk liegt auf der Integration der unterschiedlichen Prozesse sowie der einzelnen Prozessschritte zu einem Gesamtprozess, der s{\"a}mtliche Inhaltsstoffe der Silage verwertet.}, language = {de} } @article{DegeringEggertPulsetal.2010, author = {Degering, Christian and Eggert, Thorsten and Puls, Michael and Bongaerts, Johannes and Evers, Stefan and Maurer, Karl-Heinz and Jaeger, Karl-Erich}, title = {Optimization of protease secretion in Bacillus subtilis and Bacillus licheniformis by screening of homologous and herologous signal peptides}, series = {Applied and environmental microbiology}, volume = {76}, journal = {Applied and environmental microbiology}, number = {19}, publisher = {American Society for Microbiology}, address = {Washington, DC}, issn = {1098-5336 (E-Journal); 0003-6919 (Print); 0099-2240 (Print)}, doi = {10.1128/AEM.01146-10}, pages = {6370 -- 6378}, year = {2010}, abstract = {Bacillus subtilis and Bacillus licheniformis are widely used for the large-scale industrial production of proteins. These strains can efficiently secrete proteins into the culture medium using the general secretion (Sec) pathway. A characteristic feature of all secreted proteins is their N-terminal signal peptides, which are recognized by the secretion machinery. Here, we have studied the production of an industrially important secreted protease, namely, subtilisin BPN′ from Bacillus amyloliquefaciens. One hundred seventy-three signal peptides originating from B. subtilis and 220 signal peptides from the B. licheniformis type strain were fused to this secretion target and expressed in B. subtilis, and the resulting library was analyzed by high-throughput screening for extracellular proteolytic activity. We have identified a number of signal peptides originating from both organisms which produced significantly increased yield of the secreted protease. Interestingly, we observed that levels of extracellular protease were improved not only in B. subtilis, which was used as the screening host, but also in two different B. licheniformis strains. To date, it is impossible to predict which signal peptide will result in better secretion and thus an improved yield of a given extracellular target protein. Our data show that screening a library consisting of homologous and heterologous signal peptides fused to a target protein can identify more-effective signal peptides, resulting in improved protein export not only in the original screening host but also in different production strains.}, language = {en} } @article{WernerKrumbeSchumacheretal.2011, author = {Werner, Frederik and Krumbe, Christoph and Schumacher, Katharina and Groebel, Simone and Spelthahn, Heiko and Stellberg, Michael and Wagner, Torsten and Yoshinobu, Tatsuo and Selmer, Thorsten and Keusgen, Michael and Baumann, Marcus and Sch{\"o}ning, Michael Josef}, title = {Determination of the extracellular acidification of Escherichia coli by a light-addressable potentiometric sensor}, series = {Physica status solidi (a) : applications and material science. 208 (2011), H. 6}, journal = {Physica status solidi (a) : applications and material science. 208 (2011), H. 6}, publisher = {Wiley}, address = {Weinheim}, isbn = {1862-6319}, pages = {1340 -- 1344}, year = {2011}, language = {en} } @article{WernerGroebelWagneretal.2011, author = {Werner, Frederik and Groebel, Simone and Wagner, Torsten and Yoshinobu, Tatsuo and Selmer, Thorsten and Baumann, Marcus and Sch{\"o}ning, Michael Josef}, title = {{\"U}berwachung der metabolischen Aktivit{\"a}t von Mikroorganismen zur Kontrolle des biologischen Prozesses im Biogasfermenter}, series = {Biogas 2011 : Energietr{\"a}ger der Zukunft ; 6. Fachtagung, Fachtagung Braunschweig, 08. und 09. Juni 2011 / VDI Energie und Umwelt}, journal = {Biogas 2011 : Energietr{\"a}ger der Zukunft ; 6. Fachtagung, Fachtagung Braunschweig, 08. und 09. Juni 2011 / VDI Energie und Umwelt}, publisher = {VDI-Verl.}, address = {D{\"u}sseldorf}, isbn = {978-3-18-092121-1}, pages = {285 -- 286}, year = {2011}, language = {de} } @article{MartinsBlaserFeliksetal.2011, author = {Martins, Berta M. and Blaser, Martin and Feliks, Mikolaj and Ullmann, Matthias G. and Buckel, Wolfgang and Selmer, Thorsten}, title = {Structural basis for a Kolbe-type decarboxylation catalyzed by a glycyl radical enzyme}, series = {Journal of the American Chemical Society}, journal = {Journal of the American Chemical Society}, publisher = {ACS Publications}, address = {Washington, DC}, pages = {1 -- 33}, year = {2011}, language = {en} } @article{SchiffelsBaumannSelmer2011, author = {Schiffels, Johannes and Baumann, Marcus and Selmer, Thorsten}, title = {Facile analysis of short-chain fatty acids as 4-nitrophenyl esters in complex anaerobic fermentation samples by high performance liquid chromatography}, series = {Journal of Chromatography A. 1218 (2011), H. 34}, journal = {Journal of Chromatography A. 1218 (2011), H. 34}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {0021-9673}, pages = {5848 -- 5851}, year = {2011}, language = {en} } @article{BaeckerDellePoghossianetal.2011, author = {B{\"a}cker, Matthias and Delle, L. and Poghossian, Arshak and Biselli, Manfred and Zang, Werner and Wagner, P. and Sch{\"o}ning, Michael Josef}, title = {Electrochemical sensor array for bioprocess monitoring}, series = {Electrochimica Acta (2011)}, volume = {56}, journal = {Electrochimica Acta (2011)}, number = {26}, publisher = {Elsevier}, address = {Amsterdam}, pages = {9673 -- 9678}, year = {2011}, language = {en} } @article{AggarwalSinghSinghetal.2011, author = {Aggarwal, Prerna and Singh, Virendra and Singh, Arjun and Scherer, Ulrich W. and Singh, Tejvir and Singla, Madan L. and Srivastava, Alok}, title = {Physico-chemical transformations in swift heavy ion modified poly(ethyleneterephthalate)}, series = {Radiation Physics and Chemistry}, journal = {Radiation Physics and Chemistry}, publisher = {Pergamon Press}, address = {Oxford}, isbn = {0969-806X}, pages = {1 -- 28}, year = {2011}, language = {en} } @article{OosterhuisOehlschlaegerBergetal.2011, author = {Oosterhuis, Koen and {\"O}hlschl{\"a}ger, Peter and Berg, Joost H. van den and Toebes, Mireille and Gomez, Raquel and Schumacher, Ton N. and Haanen, John B.}, title = {Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7}, series = {International Journal of Cancer}, volume = {129}, journal = {International Journal of Cancer}, number = {2}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {397 -- 406}, year = {2011}, language = {en} } @article{OehlschlaegerSpiesAlvarezetal.2011, author = {{\"O}hlschl{\"a}ger, Peter and Spies, Elmar and Alvarez, Gerardo and Quetting, Michael and Groettrup, Marcus}, title = {The combination of TLR-9 adjuvantation and electroporation-mediated delivery enhances in vivo antitumor responses after vaccination with HPV-16 E7 encoding DNA}, series = {International Journal of Cancer. 128 (2011), H. 2}, journal = {International Journal of Cancer. 128 (2011), H. 2}, publisher = {Wiley}, address = {Weinheim}, isbn = {1097-0215}, pages = {473 -- 481}, year = {2011}, language = {en} } @article{ManeaLeursOrbanetal.2011, author = {Manea, Marilena and Leurs, Ulrike and Orban, Erika and Baranyai, Zsuzsa and {\"O}hlschl{\"a}ger, Peter and Marquardt, Andreas and Schulcz, Akos and Tejeda, Miguel}, title = {Enhanced Enzymatic Stability and Antitumor Activity of Daunorubicin-GnRH-III Bioconjugates Modified in Position 4}, series = {Bioconjugate Chemistry}, volume = {22}, journal = {Bioconjugate Chemistry}, number = {7}, publisher = {ACS}, address = {Washington, DC}, isbn = {1520-4812}, pages = {1320 -- 1329}, year = {2011}, language = {en} } @article{SpiessWilfriedAlvarezetal.2011, author = {Spiess, Elmar and Wilfried, Reichardt and Alvarez, Gerardo and Gottrup, Marcus and {\"O}hlschl{\"a}ger, Peter}, title = {An Artificial PAP Gene Breaks Self-tolerance and Promotes Tumor Regression in the TRAMP Model for Prostate Carcinoma}, series = {Molecular Therapy}, volume = {20}, journal = {Molecular Therapy}, number = {3}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {1525-0016}, pages = {555 -- 564}, year = {2011}, language = {en} } @article{DeppeBongaertsO'Connelletal.2011, author = {Deppe, Veronika Maria and Bongaerts, Johannes and O'Connell, Timothy and Maurer, Karl-Heinz and Meinhardt, Friedhelm}, title = {Enzymatic deglycation of Amadori products in bacteria}, series = {Applied microbiology and biotechnology}, volume = {Vol. 90}, journal = {Applied microbiology and biotechnology}, number = {Iss. 2}, publisher = {Springer}, address = {Berlin}, issn = {1432-0614 (E-Journal); 0171-1741 (Print); 0175-7598 (Print); 0340-2118 (Print)}, pages = {399 -- 406}, year = {2011}, language = {en} } @article{DeppeKlatteBongaertsetal.2011, author = {Deppe, Veronika Maria and Klatte, Stephanie and Bongaerts, Johannes and Maurer, Karl-Heinz and O'Connell, Timothy and Meinhardt, Friedhelm}, title = {Genetic control of Amadori product degradation in Bacillus subtilis via regulation of frlBONMD expression by FrlR}, series = {Applied and environmental microbiology}, volume = {Vol. 77}, journal = {Applied and environmental microbiology}, number = {No. 9}, publisher = {American Society of Mechanical Engineers (ASME)}, address = {New York}, issn = {1098-5336 (E-Journal); 0003-6919 (Print); 0099-2240 (Print)}, pages = {2839 -- 2846}, year = {2011}, language = {en} } @article{BongaertsEsserLorbachetal.2011, author = {Bongaerts, Johannes and Esser, Simon and Lorbach, Volker and Al-Momani, L{\´o}ay and M{\"u}ller, Michael A. and Franke, Dirk and Grondal, Christoph and Kurutsch, Anja and Bujnicki, Robert and Takors, Ralf and Raeven, Leon and Wubbolts, Marcel and Bovenberg, Roel and Nieger, Martin and Sch{\"u}rmann, Melanie and Trachtmann, Natalie and Kozak, Stefan and Sprenger, Georg A. and M{\"u}ller, Michael}, title = {Diversity-oriented production of metabolites derived from chorismate and their use in organic synthesis}, series = {Angewandte Chemie International Edition}, volume = {Vol. 50}, journal = {Angewandte Chemie International Edition}, number = {Iss. 34}, publisher = {Wiley}, address = {Weinheim}, issn = {1521-3773 (E-Journal); 0570-0833 (Print); 1433-7851 (Print)}, pages = {7781 -- 7786}, year = {2011}, language = {en} } @article{NiehausGaborWielandetal.2011, author = {Niehaus, F. and Gabor, E. and Wieland, S. and Siegert, Petra and Maurer, Karl-Heinz and Eck, J.}, title = {Enzymes for the laundry industries: tapping the vast metagenomic pool of alkaline proteases}, series = {Microbial biotechnology}, volume = {Vol. 4}, journal = {Microbial biotechnology}, number = {Iss. 6}, publisher = {Springer}, address = {Berlin}, issn = {1432-0614 (E-Journal); 0171-1741 (Print); 0175-7598 (Print); 0340-2118 (Print)}, pages = {767 -- 776}, year = {2011}, language = {en} } @misc{SiegertEversMarionetal.2011, author = {Siegert, Petra and Evers, Stefan and Marion, Merkel and Mussmann, Nina and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz and Schwaneberg, Ulrich and Martinez, Ronny and Jakob, Felix}, title = {Verfahren zur Anpassung eines hydrolytischen Enzyms an eine das hydrolytische Enzym stabilisierende Komponente [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 27}, year = {2011}, language = {de} } @misc{SiegertMerkelKluinetal.2011, author = {Siegert, Petra and Merkel, Marion and Kluin, Cornelia and Maurer, Karl-Heinz and O'Connell, Timothy and Wieland, Susanne and Hellmuth, Hendrik}, title = {Neue Proteasen und diese enthaltende Mittel [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 21}, year = {2011}, language = {de} } @misc{WielandSiegertSpitzetal.2011, author = {Wieland, Susanne and Siegert, Petra and Spitz, Astrid and Maurer, Karl-Heinz and O'Connell, Timothy and Pr{\"u}ser, Inken and Schiedel, Marc-Steffen and Eiting, Thomas and Sendor-M{\"u}ller, Dorota and Bastigkeit, Thorsten and Benda, Konstantin and M{\"u}ller, Sven}, title = {Lagerstabiles fl{\"u}ssiges Wasch- oder Reinigungsmittel enthaltend Proteasen [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 25}, year = {2011}, language = {de} } @article{RaabKappelKraemeretal.2011, author = {Raab, Monika and Kappel, Sven and Kr{\"a}mer, Andrea and Sanhaji, Mourad and Matthess, Yves and Kurunci-Csacsko, Elisabeth and Calzada-Wack, Julia and Rathkolb, Birgit and Rosman, Jan and Adler, Thure and Busch, Dirk H. and Esposito, Irene and Fuchs, Helmut and Gailus-Durner, Val{\´e}rie and Klingenspor, Martin and Wolf, Eckhard and S{\"a}nger, Nicole and Prinz, Florian and Hrabe de Angelis, Martin and Seibler, Jost and Yuan, Juping and Bergmann, Martin and Knecht, Rainald and Kreft, Bertolt and Strebhardt, Klaus}, title = {Toxicity modelling of Plk1-targeted therapies in genetically engineered mice and cultured primary mammalian cells}, series = {Nature Communications}, volume = {2}, journal = {Nature Communications}, number = {395}, publisher = {Nature}, address = {London}, issn = {2041-1723}, doi = {10.1038/ncomms1395}, pages = {1 -- 11}, year = {2011}, language = {en} } @article{HasegawaKapelyukhTaharaetal.2011, author = {Hasegawa, Maki and Kapelyukh, Yury and Tahara, Harunobu and Seibler, Jost and Rode, Anja and Krueger, Sylvia and Lee, Dongtao N. and Wolf, C. Roland and Scheer, Nico}, title = {Quantitative prediction of human pregnane X receptor and cytochrome P450 3A4 mediated drug-drug interaction in a novel multiple humanized mouse line}, series = {Molecular Pharmacology}, volume = {80}, journal = {Molecular Pharmacology}, number = {33}, publisher = {ASPET}, address = {Bethesda, Md.}, issn = {1521-0111}, doi = {10.1124/mol.111.071845}, pages = {518 -- 528}, year = {2011}, language = {en} } @article{JordanKruegerWillmesetal.2011, author = {Jordan, Sabine D. and Kr{\"u}ger, Markus and Willmes, Diana M. and Redemann, Nora and Wunderlich, F. Thomas and Br{\"o}nneke, Hella S. and Merkwirth, Carsten and Kashkar, Hamid and Olkkonen, Vesa M. and B{\"o}ttger, Thomas and Braun, Thomas and Seibler, Jost and Br{\"u}ning, Jens C.}, title = {Obesity-induced overexpression of miRNA-143 inhibits insulin-stimulated AKT activation and impairs glucose metabolism}, series = {Nature Cell Biology}, volume = {13}, journal = {Nature Cell Biology}, number = {4}, publisher = {Nature}, address = {New York}, issn = {1465-7392}, doi = {10.1038/ncb2211}, pages = {434 -- 446}, year = {2011}, abstract = {The contribution of altered post-transcriptional gene silencing to the development of insulin resistance and type 2 diabetes mellitus so far remains elusive. Here, we demonstrate that expression of microRNA (miR)-143 and 145 is upregulated in the liver of genetic and dietary mouse models of obesity. Induced transgenic overexpression of miR-143, but not miR-145, impairs insulin-stimulated AKT activation and glucose homeostasis. Conversely, mice deficient for the miR-143-145 cluster are protected from the development of obesity-associated insulin resistance. Quantitative-mass-spectrometry-based analysis of hepatic protein expression in miR-143-overexpressing mice revealed miR-143-dependent downregulation of oxysterol-binding-protein-related protein (ORP) 8. Reduced ORP8 expression in cultured liver cells impairs the ability of insulin to induce AKT activation, revealing an ORP8-dependent mechanism of AKT regulation. Our experiments provide direct evidence that dysregulated post-transcriptional gene silencing contributes to the development of obesity-induced insulin resistance, and characterize the miR-143-ORP8 pathway as a potential target for the treatment of obesity-associated diabetes.}, language = {en} } @article{InagakiSleddensLinkelsWassenaaretal.2011, author = {Inagaki, Akiko and Sleddens-Linkels, Esther and Wassenaar, Evelyne and Ooms, Marja and Cappellen, Wiggert A. van and Hoeijmakers, Jan H. J. and Seibler, Jost and Vogt, Thomas F. and Shin, Myung K. and Grootegoed, J. Anton and Baarends, Willy M.}, title = {Meiotic functions of RAD18}, series = {Journal of Cell Science}, volume = {124}, journal = {Journal of Cell Science}, number = {16}, publisher = {Company of Biologists Limited}, address = {Cambridge}, issn = {1477-9137}, doi = {10.1242/jcs.081968}, pages = {2837 -- 2850}, year = {2011}, language = {en} } @article{SiekerNeunerDimitrovaetal.2011, author = {Sieker, Tim and Neuner, Andreas and Dimitrova, Darina and Tippk{\"o}tter, Nils and Muffler, Kai and Bart, Hans-J{\"o}rg and Heinzle, Elmar and Ulber, Roland}, title = {Ethanol production from grass silage by simultaneous pretreatment, saccharification and fermentation: First steps in the process development}, series = {Engineering in Life Sciences}, volume = {11}, journal = {Engineering in Life Sciences}, number = {4}, publisher = {Wiley}, address = {Weinheim}, doi = {10.1002/elsc.201000160}, pages = {436 -- 442}, year = {2011}, abstract = {Grass silage provides a great potential as renewable feedstock. Two fractions of the grass silage, a press juice and the fiber fraction, were evaluated for their possible use for bioethanol production. Direct production of ethanol from press juice is not possible due to high concentrations of organic acids. For the fiber fraction, alkaline peroxide or enzymatic pretreatment was used, which removes the phenolic acids in the cell wall. In this study, we demonstrate the possibility to integrate the enzymatic pretreatment with a simultaneous saccharification and fermentation to achieve ethanol production from grass silage in a one-process step. Achieved yields were about 53 g ethanol per kg silage with the alkaline peroxide pretreatment and 91 g/kg with the enzymatic pretreatment at concentrations of 8.5 and 14.6 g/L, respectively. Furthermore, it was shown that additional supplementation of the fermentation medium with vitamins, trace elements and nutrient salts is not necessary when the press juice is directly used in the fermentation step.}, language = {en} } @article{PothMonzonTippkoetteretal.2011, author = {Poth, Sebastian and Monzon, Magaly and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Lignocellulosic biorefinery: Process integration of hydrolysis and fermentation (SSF process)}, series = {Holzforschung}, volume = {65}, journal = {Holzforschung}, number = {5}, publisher = {De Gruyter}, address = {Berlin}, pages = {633 -- 637}, year = {2011}, abstract = {The aim of the present work is the process integration and the optimization of the enzymatic hydrolysis of wood and the following fermentation of the products to ethanol. The substrate is a fiber fraction obtained by organosolv pre-treatment of beech wood. For the ethanol production, a co-fermentation by two different yeasts (Saccharomyces cerevisiae and Pachysolen tannophilus) was carried out to convert glucose as well as xylose. Two approaches has been followed: 1. A two step process, in which the hydrolysis of the fiber fraction and the fermentation to product are separated from each other. 2. A process, in which the hydrolysis and the fermentation are carried out in one single process step as simultaneous saccharification and fermentation (SSF). Following the first approach, a yield of about 0.15 g ethanol per gram substrate can be reached. Based on the SSF, one process step can be saved, and additionally, the gained yield can be raised up to 0.3 g ethanol per gram substrate.}, language = {en} } @incollection{HahnKellyMuffleretal.2011, author = {Hahn, Thomas and Kelly, Svenja and Muffler, Kai and Tippk{\"o}tter, Nils and Ulber, Roland}, title = {Extraction of lignocellulose and algae for the production of bulk and fine chemicals}, series = {Industrial scale natural products extraction}, booktitle = {Industrial scale natural products extraction}, editor = {Hans-J{\"o}rg, Bart and Pilz, Stephan}, publisher = {Wiley-VCH}, address = {Weinheim}, isbn = {978-3-527-32504-7 (Print)}, doi = {10.1002/9783527635122}, pages = {221 -- 245}, year = {2011}, language = {en} } @incollection{MufflerPothSiekeretal.2011, author = {Muffler, Kai and Poth, Sabastian and Sieker, Tim and Tippk{\"o}tter, Nils and Ulber, Roland and Sell, Dieter}, title = {Bio-feedstocks}, series = {Comprehensive biotechnology : principles and practices in industry, agcriculture, medicine and the environment. Volume 2: Engineering fundamentals of biotechnology}, booktitle = {Comprehensive biotechnology : principles and practices in industry, agcriculture, medicine and the environment. Volume 2: Engineering fundamentals of biotechnology}, editor = {Moo-Young, Murray}, edition = {2. edition}, publisher = {Elsevier}, address = {Amsterdam}, isbn = {978-0-444-53352-4}, doi = {10.1016/B978-0-08-088504-9.00088-X}, pages = {93 -- 101}, year = {2011}, language = {en} } @article{TippkoetterWollnyKampeisetal.2011, author = {Tippk{\"o}tter, Nils and Wollny, S. and Kampeis, P. and Oster, J. and Schneider, H. and Ulber, R.}, title = {Magnetseparation von Proteinen : Separation von Zielmolek{\"u}len durch hochselektive Aptamere}, series = {GIT Labor-Fachzeitschrift}, volume = {55}, journal = {GIT Labor-Fachzeitschrift}, number = {10}, publisher = {Wiley}, address = {Weinheim}, pages = {666}, year = {2011}, abstract = {Durch die Kombination von Oligonukleotid-Liganden (Aptameren) hoher Bindungsaffinit{\"a}ten mit hochselektiv abtrennbaren magnetisierbaren Mikropartikeln wird eine einstufige Separation von Zielmolek{\"u}len aus mikrobiologischen Produktionsans{\"a}tzen m{\"o}glich. Die Aptamere werden hierf{\"u}r reversibel auf den Partikeloberfl{\"a}chen gebunden und f{\"u}r die spezifische Isolierung von Bioprodukten eingesetzt. Die Abtrennung der beladenen Partikel erfolgt durch einen neuen Rotor-Stator-Separator mit Hochgradient-Magnetfeld.}, language = {de} } @incollection{UlberMufflerTippkoetteretal.2011, author = {Ulber, Roland and Muffler, Kai and Tippk{\"o}tter, Nils and Hirth, Thomas and Sell, Dieter}, title = {Introduction to Renewable Resources in the Chemical Industry}, series = {Renewable raw materials : new feedstocks for the chemical industry}, booktitle = {Renewable raw materials : new feedstocks for the chemical industry}, editor = {Ulber, Roland and Sell, Dieter and Hirth, Thomas}, edition = {1. Auflage}, publisher = {Wiley-VCH-Verlag}, address = {Weinheim}, isbn = {978-3-527-32548-1}, pages = {1 -- 6}, year = {2011}, language = {de} } @article{ImmelGrothHuhnetal.2011, author = {Immel, Timo A. and Groth, Ulrich and Huhn, Thomas and {\"O}hlschl{\"a}ger, Peter}, title = {Titanium salan complexes displays strong antitumor properties in vitro and in vivo in mice}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {3}, publisher = {Plos}, address = {San Francisco, California, US}, doi = {10.1371/journal.pone.0017869}, pages = {e17869}, year = {2011}, abstract = {The anticancer activity of titanium complexes has been known since the groundbreaking studies of K{\"o}pf and K{\"o}pf-Maier on titanocen dichloride. Unfortunately, possibly due to their fast hydrolysis, derivatives of titanocen dichloride failed in clinical studies. Recently, the new family of titanium salan complexes containing tetradentate ONNO ligands with anti-cancer properties has been discovered. These salan complexes are much more stabile in aqueous media. In this study we describe the biological activity of two titanium salan complexes in a mouse model of cervical cancer. High efficiency of this promising complex family was demonstrated for the first time in vivo. From these data we conclude that titanium salan complexes display very strong antitumor properties exhibiting only minor side effects. Our results may influence the chemotherapy with metallo therapeutics in the future.}, language = {en} } @inproceedings{FeuerriegelPookWerschetal.2012, author = {Feuerriegel, Uwe and Pook, Michael and Wersch, Gregor and Wittenhorst, Simon and Becker, J{\"u}rgen and Ecker, Markus and Hoffmann, Ulrich and Kunz, Ulrich}, title = {Simulation von W{\"a}rme{\"u}bertragungsprozessen}, year = {2012}, abstract = {Mit freundlicher Genehmigung der Autoren und des Oldenbourg Industrieverlags https://www.oldenbourg-industrieverlag.de/de/9783835633223-33223 erschienen als Beitrag im Tagungsband zur AALE-Tagung 2012. 9. Fachkonferenz 4.-5. Mai 2012, Aachen, Fachhochschule. ISBN 9783835633223 S 5-1 S. 127-135 Es werden Ergebnisse unterschiedlicher Projekte aus dem Bereich der Simulation von W{\"a}rme{\"u}bertragungsprozessen mit Excel-VBA vorgestellt. - Thermische Behandlung hochviskoser Fruchtzubereitungen, verschiedene Projekte und Kooperationen mit der Zentis GmbH \& Co. KG, Aachen (J. Becker, U. Feuerriegel, G. Wersch). - Untersuchung des dynamischen Verhaltens von dampfbeheizten Ethylen-Verdampfern. Projekt mit der TGE Gas Engineering GmbH, Bonn (M. Ecker, U. Feuerriegel, U. Hoffmann, S. Wittenhorst). - Dynamische Simulation des axialen Temperaturverlaufs von elektrisch beheizten Rohrreaktoren. Kooperation mit dem Institut f{\"u}r Chemische Verfahrenstechnik, TU Clausthal (U. Feuerriegel, U. Kunz, M. Pook, S. Wittenhorst).}, subject = {W{\"a}rme{\"u}bertragung}, language = {de} } @article{LeursMezoOehlschlaegeretal.2012, author = {Leurs, Ulrike and Mezo, Gabor and {\"O}hlschl{\"a}ger, Peter and Orban, Erika and Marquard, Andrea and Manea, Marilena}, title = {Design, synthesis, in vitro stability and cytostatic effect of multifunctional anticancer drug-bioconjugates containing GnRH-III as a targeting moiety}, series = {Peptide Science}, volume = {98}, journal = {Peptide Science}, number = {1}, publisher = {Wiley}, address = {New York, NY}, issn = {1097-0282}, doi = {10.1002/bip.21640}, pages = {1 -- 10}, year = {2012}, abstract = {Bioconjugates containing the GnRH-III hormone decapeptide as a targeting moiety are able to deliver chemotherapeutic agents specifically to cancer cells expressing GnRH receptors, thereby increasing their local efficacy while limiting the peripheral toxicity. However, the number of GnRH receptors on cancer cells is limited and they desensitize under continuous hormone treatment. A possible approach to increase the receptor mediated tumor targeting and consequently the cytostatic effect of the bioconjugates would be the attachment of more than one chemotherapeutic agent to one GnRH-III molecule. Here we report on the design, synthesis and biochemical characterization of multifunctional bioconjugates containing GnRH-III as a targeting moiety and daunorubicin as a chemotherapeutic agent. Two different drug design approaches were pursued. The first one was based on the bifunctional [4Lys]-GnRH-III (Glp-His-Trp-Lys-His-Asp-Trp-Lys-Pro-Gly-NH2) containing two lysine residues in positions 4 and 8, whose ϵ-amino groups were used for the coupling of daunorubicin. In the second drug design, the native GnRH-III (Glp-His-Trp-Ser-His-Asp-Trp-Lys-Pro-Gly-NH2) was used as a scaffold; an additional lysine residue was coupled to the ϵ-amino group of 8Lys in order to generate two free amino groups available for conjugation of daunorubicin. The in vitro stability/degradation of all synthesized compounds was investigated in human serum, as well as in the presence of rat liver lysosomal homogenate. Their cellular uptake was determined on human breast cancer cells and the cytostatic effect was evaluated on human breast, colon and prostate cancer cell lines. Compared with a monofunctional compound, both drug design approaches resulted in multifunctional bioconjugates with increased cytostatic effect.}, language = {en} } @article{BaeckerRaueSchusseretal.2012, author = {B{\"a}cker, Matthias and Raue, Markus and Schusser, Sebastian and Jeitner, C. and Breuer, L. and Wagner, P. and Poghossian, Arshak and F{\"o}rster, Arnold and Mang, Thomas and Sch{\"o}ning, Michael Josef}, title = {Microfluidic chip with integrated microvalves based on temperature- and pH-responsive hydrogel thin films}, series = {Physica Status Solidi (a)}, volume = {209}, journal = {Physica Status Solidi (a)}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201100763}, pages = {839 -- 845}, year = {2012}, abstract = {Two types of microvalves based on temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm) and pH-responsive poly(sodium acrylate) (PSA) hydrogel films have been developed and tested. The PNIPAAm and PSA hydrogel films were prepared by means of in situ photopolymerization directly inside the fluidic channel of a microfluidic chip fabricated by combining Si and SU-8 technologies. The swelling/shrinking properties and height changes of the PNIPAAm and PSA films inside the fluidic channel were studied at temperatures of deionized water from 14 to 36 °C and different pH values (pH 3-12) of Titrisol buffer, respectively. Additionally, in separate experiments, the lower critical solution temperature (LCST) of the PNIPAAm hydrogel was investigated by means of a differential scanning calorimetry (DSC) and a surface plasmon resonance (SPR) method. Mass-flow measurements have shown the feasibility of the prepared hydrogel films to work as an on-chip integrated temperature- or pH-responsive microvalve capable to switch the flow channel on/off.}, language = {en} } @article{AggarwalDhimanKumaretal.2012, author = {Aggarwal, P. and Dhiman, S. and Kumar, G. and Scherer, Ulrich W. and Singla, M. L. and Srivastava, A.}, title = {Optical study of poly(ethyleneterephthalate) modified by different ionizing radiation dose}, series = {Indian Journal of Pure and Applied Physics}, volume = {50}, journal = {Indian Journal of Pure and Applied Physics}, number = {2}, issn = {0019-5596}, pages = {129 -- 132}, year = {2012}, abstract = {Thin films of poly(ethyleneterephthalate) [PET]were exposed to radiation dose ranging from 10 to 30 kGy by using gamma rays in the range 12.8-177.8 MGy using swift light ions of hydrogen. There was no effect of the radiation dose on the optical behaviour of PET as a result of exposure to radiation dose up to 30 kGy brought about by gamma rays but a significant decrease in the optical band gap values was observed when PET was exposed to swift light ions of hydrogen. The data obtained are discussed in terms of optical studies carried out on PET using swift heavy ions.}, language = {en} } @article{WernerGroebelKrumbeetal.2012, author = {Werner, Frederik and Groebel, Simone and Krumbe, Christoph and Wagner, Torsten and Selmer, Thorsten and Yoshinobu, Tatsuo and Baumann, Marcus and Sch{\"o}ning, Michael Josef}, title = {Nutrient concentration-sensitive microorganism-based biosensor}, series = {Physica Status Solidi (a)}, volume = {209}, journal = {Physica Status Solidi (a)}, number = {5}, publisher = {Wiley-VCH}, address = {Weinheim}, issn = {1862-6319}, doi = {10.1002/pssa.201100801}, pages = {900 -- 904}, year = {2012}, language = {en} } @inproceedings{FeuerriegelWittenhorstHoffmannetal.2012, author = {Feuerriegel, Uwe and Wittenhorst, Simon and Hoffmann, Ulrich and Pook, Michael}, title = {Simulation von W{\"a}rme{\"u}bertragungsprozessen}, series = {Tagungsband zur AALE-Tagung 2012 : 9. Fachkonferenz}, booktitle = {Tagungsband zur AALE-Tagung 2012 : 9. Fachkonferenz}, publisher = {Oldenbourg Industrieverlag}, address = {M{\"u}nchen}, isbn = {978-3-8356-3305-6}, pages = {127 -- 136}, year = {2012}, language = {de} } @techreport{VaessenOhmeManderscheid2012, author = {Vaeßen, Christiane and Ohme, H. and Manderscheid, D.}, title = {Endbericht Projekt Immotherm : Vorhabensbezeichnung: KMU-innovativ-Verbundvorhaben "Einsatz immobilisierter Mikroorganismen zur Ent{\"o}lung und Entsalzung von Kondensatwasser bei hohen Prozesstemperaturen" : Laufzeit des Vorhabens: 01.03.2009-31.08.2011 : F{\"o}rderkennzeichen: 01LY0816A, 01LY0816B, 01LY0816C}, pages = {71 S. : zahlr. Ill. u. graph. Darst.}, year = {2012}, language = {de} } @article{BorgmeierBongaertsMeinhardt2012, author = {Borgmeier, Claudia and Bongaerts, Johannes and Meinhardt, Friedhelm}, title = {Genetic analysis of the Bacillus licheniformis degSU operon and the impact of regulatory mutations on protease production}, series = {Journal of biotechnology}, volume = {159}, journal = {Journal of biotechnology}, number = {1-2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2012.02.011}, pages = {12 -- 20}, year = {2012}, abstract = {Disruption experiments targeted at the Bacillus licheniformis degSU operon and GFP-reporter analysis provided evidence for promoter activity immediately upstream of degU. pMutin mediated concomitant introduction of the degU32 allele - known to cause hypersecretion in Bacillus subtilis - resulted in a marked increase in protease activity. Application of 5-fluorouracil based counterselection through establishment of a phosphoribosyltransferase deficient Δupp strain eventually facilitated the marker-free introduction of degU32 leading to further protease enhancement achieving levels as for hypersecreting wild strains in which degU was overexpressed. Surprisingly, deletion of rapG - known to interfere with DegU DNA-binding in B. subtilis - did not enhance protease production neither in the wild type nor in the degU32 strain. The combination of degU32 and Δupp counterselection in the type strain is not only equally effective as in hypersecreting wild strains with respect to protease production but furthermore facilitates genetic strain improvement aiming at biological containment and effectiveness of biotechnological processes.}, language = {en} } @article{SchoeningBiselliSelmeretal.2012, author = {Sch{\"o}ning, Michael Josef and Biselli, Manfred and Selmer, Thorsten and {\"O}hlschl{\"a}ger, Peter and Baumann, Marcus and F{\"o}rster, Arnold and Poghossian, Arshak}, title = {Forschung „zwischen" den Disziplinen: das Institut f{\"u}r Nano- und Biotechnologien}, series = {Analytik news : das Online-Labormagazin f{\"u}r Labor und Analytik}, volume = {Publ. online}, journal = {Analytik news : das Online-Labormagazin f{\"u}r Labor und Analytik}, publisher = {Dr. Beyer Internet-Beratung}, address = {Ober-Ramstadt}, pages = {11 Seiten}, year = {2012}, abstract = {"Biologie trifft Mikroelektronik", das Motto des Instituts f{\"u}r Nano- und Biotechnologien (INB) an der FH Aachen, unterstreicht die zunehmende Bedeutung interdisziplin{\"a}r gepr{\"a}gter Forschungsaktivit{\"a}ten. Der thematische Zusammenschluss grundst{\"a}ndiger Disziplinen, wie die Physik, Elektrotechnik, Chemie, Biologie sowie die Materialwissenschaften, l{\"a}sst neue Forschungsgebiete entstehen, ein herausragendes Beispiel hierf{\"u}r ist die Nanotechnologie: Hier werden neue Werkstoffe und Materialien entwickelt, einzelne Nanopartikel oder Molek{\"u}le und deren Wechselwirkung untersucht oder Schichtstrukturen im Nanometerbereich aufgebaut, die neue und vorher nicht bekannte Eigenschaften hervorbringen. Vor diesem Hintergrund b{\"u}ndelt das im Jahre 2006 gegr{\"u}ndete INB die an der FH Aachen vorhandenen Kompetenzen von derzeit insgesamt sieben Laboratorien auf den Gebieten der Halbleitertechnik und Nanoelektronik, Nanostrukturen und DNA-Sensorik, der Chemo- und Biosensorik, der Enzymtechnologie, der Mikrobiologie und Pflanzenbiotechnologie, der Zellkulturtechnik, sowie der Roten Biotechnologie synergetisch. In der Nano- und Biotechnologie steckt außergew{\"o}hnliches Potenzial! Nicht zuletzt deshalb stellen sich die Forscher der Herausforderung, in diesem Bereich gemeinsam zu forschen und Schnittstellen zu nutzen, um so bei der Gestaltung neuartiger Ideen und Produkte mitzuwirken, die zuk{\"u}nftig unser allt{\"a}gliches Leben ver{\"a}ndern werden. Im Folgenden werden die verschiedenen Forschungsbereiche kurz zusammenfassend vorgestellt und vorhandene Interaktionen anhand von exemplarisch ausgew{\"a}hlten, aktuellen Forschungsprojekten skizziert.}, language = {de} } @article{RibitschHeumannKarletal.2012, author = {Ribitsch, D. and Heumann, S. and Karl, W. and Gerlach, J. and Leber, R. and Birner-Gruenberger, R. and Gruber, K. and Eiteljoerg, I. and Remler, P. and Siegert, Petra and Lange, J. and Maurer, Karl-Heinz and Berg, G. and Guebitz, G. M. and Schwab, H.}, title = {Extracellular serine proteases from Stenotrophomonas maltophilia: Screening, isolation and heterologous expression in E. coli}, series = {Journal of biotechnology}, volume = {157}, journal = {Journal of biotechnology}, number = {1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1873-4863 (E-Journal); 0168-1656 (Print)}, doi = {10.1016/j.jbiotec.2011.09.025}, pages = {140 -- 147}, year = {2012}, abstract = {A large strain collection comprising antagonistic bacteria was screened for novel detergent proteases. Several strains displayed protease activity on agar plates containing skim milk but were inactive in liquid media. Encapsulation of cells in alginate beads induced protease production. Stenotrophomonas maltophilia emerged as best performer under washing conditions. For identification of wash-active proteases, four extracellular serine proteases called StmPr1, StmPr2, StmPr3 and StmPr4 were cloned. StmPr2 and StmPr4 were sufficiently overexpressed in E. coli. Expression of StmPr1 and StmPr3 resulted in unprocessed, insoluble protein. Truncation of most of the C-terminal domain which has been identified by enzyme modeling succeeded in expression of soluble, active StmPr1 but failed in case of StmPr3. From laundry application tests StmPr2 turned out to be a highly wash-active protease at 45 °C. Specific activity of StmPr2 determined with suc-l-Ala-l-Ala-l-Pro-l-Phe-p-nitroanilide as the substrate was 17 ± 2 U/mg. In addition we determined the kinetic parameters and cleavage preferences of protease StmPr2.}, language = {en} } @misc{MaurerO'ConnellSiegertetal.2012, author = {Maurer, Karl-Heinz and O'Connell, Timothy and Siegert, Petra and Weber, Thomas and Tondera, Susanne and Hellmuth, Hendrik}, title = {Fl{\"u}ssige Tensidzubereitung enthaltend Lipase und Phosphonat [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 22}, year = {2012}, language = {de} } @misc{SiegertMerkelHellmuthetal.2012, author = {Siegert, Petra and Merkel, Marion and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz}, title = {Stabilisierte fl{\"u}ssige enzymhaltige Tensidzubereitung (Einsatz einer das hydrolytische Enzym stabilisierenden Komponente, die eine Phenylalkyldicarbons{\"a}ure umfasst) [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 15}, year = {2012}, language = {de} } @misc{SiegertMerkelHellmuthetal.2012, author = {Siegert, Petra and Merkel, Marion and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz}, title = {Stabilisierte fl{\"u}ssige enzymhaltige Tensidzubereitung (durch den Einsatz einer das hydrolytische Enzym stabilisierende Komponente, die eine mehrfach substituierte Benzolcarbons{\"a}ure umfasst, die an mindestens zwei Kohlenstoffatomen des Benzolrestes eine Carboxylgruppe aufweist) [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 16}, year = {2012}, language = {de} } @misc{SiegertMerkelHellmuthetal.2012, author = {Siegert, Petra and Merkel, Marion and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz}, title = {Stabilisierte fl{\"u}ssige enzymhaltige Tensidzubereitung (Einsatz einer das hydrolytische Enzym stabilisierende Komponente, die eine Phthaloylglutamins{\"a}ure und/oder eine Phthaloylasparagins{\"a}ure umfasst) [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 16}, year = {2012}, language = {de} } @misc{SiegertMerkelHellmuthetal.2012, author = {Siegert, Petra and Merkel, Marion and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz}, title = {Stabilisierte fl{\"u}ssige enzymhaltige Tensidzubereitung (Einsatz einer das hydrolytische Enzym stabilisierende Komponente, die eine Aminophthals{\"a}ure umfasst) [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 16}, year = {2012}, language = {de} } @misc{SiegertMerkelHellmuthetal.2012, author = {Siegert, Petra and Merkel, Marion and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz}, title = {Stabilisierte fl{\"u}ssige enzymhaltige Tensidzubereitung (Einsatz einer das hydrolytische Enzym stabilisierende Komponente, die eine Oligoamino-biphenyl-oligocarbons{\"a}ure umfasst) [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 16}, year = {2012}, language = {de} } @misc{SiegertMerkelHellmuthetal.2012, author = {Siegert, Petra and Merkel, Marion and Hellmuth, Hendrik and O'Connell, Timothy and Maurer, Karl-Heinz}, title = {Stabilisierte fl{\"u}ssige enzymhaltige Tensidzubereitung (Einsatz einer das hydrolytische Enzym stabilisierende Komponente, die ein Monosaccharidglycerat umfasst) [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 17}, year = {2012}, language = {de} } @misc{SiegertSchwanebergMartinezMoyaetal.2012, author = {Siegert, Petra and Schwaneberg, Ulrich and Martinez Moya, Ronny and Merkel, Marion and Spitz, Astrid and Wieland, Susanne and Hellmuth, Hendrik and Maurer, Karl-Heinz}, title = {Leistungsverbesserte Proteasevariante [Offenlegungsschrift]}, publisher = {Deutsches Patent- und Markenamt / Europ{\"a}isches Patentamt / WIPO}, address = {M{\"u}nchen / Den Hague / Genf}, pages = {1 -- 29}, year = {2012}, language = {de} } @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} }