TY - JOUR A1 - Seibler, Jost A1 - Bode, Jürgen T1 - Double-reciprocal crossover mediated by FLP-recombinase: a concept and an assay JF - Biochemistry Y1 - 1997 SN - 1520-4995 VL - 36 IS - 7 SP - 1740 EP - 1747 ER - TY - JOUR A1 - Bode, J. A1 - Bartsch, J. A1 - Boulikas, T. A1 - Iber, M. A1 - Mielke, C. A1 - Schübeler, D. A1 - Seibler, Jost A1 - Benham, C. T1 - Transcription-promoting genomic sites in mammalia: their elucidation and architectural principles JF - Gene therapy & molecular biology Y1 - 1998 SN - 1529-9120 VL - 1 IS - 1 SP - 1 EP - 29 ER - TY - JOUR A1 - Iber, Michaela A1 - Schübeler, Dirk A1 - Seibler, Jost A1 - Höxter, Maria A1 - Bode, Jürgen T1 - Efficient FACS selection procedure for cells undergoing Flp-mediated site-specific conversions JF - Technical Tips Online Y1 - 1998 U6 - https://doi.org/10.1016/S1366-2120(08)70132-6 VL - 4 IS - 1 SP - 25 EP - 29 ER - TY - JOUR A1 - Henken, F. E. A1 - Oosterhuis, K. A1 - Öhlschläger, Peter A1 - Bosch, L. A1 - Hooijberg, E. A1 - Haanen, J. B. A. G. A1 - Steenbergen, R. D. M. T1 - Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7 JF - Vaccine N2 - Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of ‘gene-shuffled’ (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies. Y1 - 2012 U6 - https://doi.org/10.1016/j.vaccine.2012.04.013 SN - 0264-410X VL - 30 IS - 28 SP - 4259 EP - 4266 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Immel, Timo A1 - Grützke, Martin A1 - Späte, Anne-Katrin A1 - Groth, Ulrich A1 - Öhlschläger, Peter A1 - Huhn, Thomas T1 - Synthesis and X-ray structure analysis of a heptacoordinate titanium(IV)-bis-chelate with enhanced in vivo antitumor efficacy JF - Chemical Communications N2 - Chelate stabilization of a titanium(IV)–salan alkoxide by ligand exchange with 2,6-pyridinedicarboxylic acid (dipic) resulted in heptacoordinate complex 3 which is not redox-active, stable on silica gel and has increased aqueous stability. 3 is highly toxic in HeLa S3 and Hep G2 and has enhanced antitumor efficacy in a mouse cervical-cancer model. Y1 - 2012 U6 - https://doi.org/10.1039/C2CC31624B SN - 1364-548X VL - 48 IS - 46 SP - 5790 EP - 5792 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Fellin, Wolfgang A1 - King, Julian A1 - Kirsch, Ansgar A1 - Oberguggenberger, Michael T1 - Uncertainty modelling and sensitivity analysis of tunnel face stability JF - Structural safety N2 - This paper proposes an approach to the choice and evaluation of engineering models with the aid of a typical application in geotechnics. An important issue in the construction of shallow tunnels, especially in weak ground conditions, is the tunnel face stability. Various theoretical and numerical models for predicting the necessary support pressure have been put forth in the literature. In this paper, we combine laboratory experiments performed at the University of Innsbruck with current methods of uncertainty and sensitivity analysis for assessing adequacy, predictive power and robustness of the models. The major issues are the handling of the twofold uncertainty of test results and of model predictions as well as the decision about what are the influential input parameters. Y1 - 2010 U6 - https://doi.org/10.1016/j.strusafe.2010.06.001 SN - 0167-4730 VL - 32 IS - 6 SP - 402 EP - 410 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Kirsch, Ansgar T1 - Experimental investigation of the face stability of shallow tunnels in sand JF - Acta Geotechnica N2 - Various models have been proposed for the prediction of the necessary support pressure at the face of a shallow tunnel. To assess their quality, the collapse of a tunnel face was modelled with small-scale model tests at single gravity. The development of the failure mechanism and the support force at the face in dry sand were investigated. The observed displacement patterns show a negligible influence of overburden on the extent and evolution of the failure zone. The latter is significantly influenced, though, by the initial density of the sand: in dense sand a chimney-wedge-type collapse mechanism developed, which propagated towards the soil surface. Initially, loose sand did not show any discrete collapse mechanism. The necessary support force was neither influenced by the overburden nor the initial density. A comparison with quantitative predictions by several theoretical models showed that the measured necessary support pressure is overestimated by most of the models. Those by Vermeer/Ruse and Léca/Dormieux showed the best agreement to the measurements. Y1 - 2010 U6 - https://doi.org/10.1007/s11440-010-0110-7 SN - 1861-1125 VL - 5 IS - 1 SP - 43 EP - 62 PB - Springer CY - Berlin ER - TY - JOUR A1 - Kolymbas, Dimitrios A1 - Fellin, W. A1 - Kirsch, Ansgar T1 - Squeezing due to stress relaxation in foliated rock JF - International journal for numerical and analytical methods in geomechanics Y1 - 2006 U6 - https://doi.org/10.1002/nag.530 SN - 1096-9853 (E-Journal); 0363-9061 (Print) VL - Vol. 30 IS - Iss. 13 SP - 1357 EP - 1367 ER - TY - JOUR A1 - Scheer, Nico A1 - Snaith, Mike A1 - Wolf, C. Roland A1 - Seibler, Jost T1 - Generation and utility of genetically humanized mouse models JF - Drug Discovery Today Y1 - 2013 U6 - https://doi.org/10.1016/j.drudis.2013.07.007 SN - 1359-6446 VL - Vol 18 IS - 23-24 SP - 1200 EP - 1211 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Bouwman, Peter A1 - Gulden, Hanneke van der A1 - Heijden, Ingrid van der A1 - Drost, Rinske A1 - Klijn, Christiaan N. A1 - Prasetyanti, Pramudita A1 - Pieterse, Mark A1 - Wientjens, Ellen A1 - Seibler, Jost A1 - Hogervorst, Frank B. L. A1 - Jonkers, Jos T1 - A High-Throughput Functional Complementation Assay for Classification of BRCA1 Missense Variants JF - Cancer Discovery Y1 - 2013 U6 - https://doi.org/10.1158/2159-8290.CD-13-0094 SN - 2159-8290 IS - 3 SP - 1142 EP - 1152 ER -