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 - TY - JOUR A1 - Michalak, Ewa Malgorzata A1 - Nacerddine, Karim A1 - Pietersen, Alexandra A1 - Beuger, Vincent A1 - Pawlitzky, Inka A1 - Cornelissen-Steijger, Paulien A1 - Wientjens, Ellen A1 - Tanger, Ellen A1 - Seibler, Jost A1 - Lohuizen, Maarten van A1 - Jonkers, Jos T1 - Polycomb group gene Ezh2 regulates mammary gland morphogenesis and maintains the luminal progenitor pool JF - Stem Cells Y1 - 2013 U6 - https://doi.org/10.1002/stem.1437 SN - 1549-4918 VL - Vol 31 IS - 9 SP - 1910 EP - 1920 PB - Oxford University Press CY - Oxford ER - TY - JOUR A1 - Gebeshuber, Christoph A. A1 - Kornauth, Christoph A1 - Dong, Lihua A1 - Sierig, Ralph A1 - Seibler, Jost A1 - Reiss, Martina A1 - Tauber, Stefanie A1 - Bilban, Martin A1 - Wang, Shijun A1 - Kain, Renate A1 - Böhmig, Georg A. A1 - Moeller, Marcus J. A1 - Gröne, Hermann-Josef A1 - Englert, Christoph A1 - Martinez, Javier A1 - Kerjaschki, Dontscho T1 - Focal segmental glomerulosclerosis is induced by microRNA-193a and its downregulation of WT1 JF - Nature Medicine Y1 - 2013 U6 - https://doi.org/10.1038/nm.3142 SN - 1078-8956 VL - 19 IS - 4 SP - 481 EP - 487 ER - TY - JOUR A1 - Kornfeld, Jan-Wilhelm A1 - Baitzel, Catherina A1 - Könner, A. Christine A1 - Nicholls, Hayley T. A1 - Vogt, Merly C. A1 - Herrmanns, Karolin A1 - Scheja, Ludger A1 - Haumaitre, Cécile A1 - Wolf, Anna M. A1 - Knippschild, Uwe A1 - Seibler, Jost A1 - Cereghini, Silvia A1 - Heeren, Joerg A1 - Stoffel, Markus A1 - Brüning, Jens C. T1 - Obesity-induced overexpression of miR-802 impairs glucose metabolism through silencing of Hnf1b JF - Nature Y1 - 2013 SN - 0028-0836 U6 - https://doi.org/10.1038/nature11793 VL - 494 IS - 7435 SP - 111 EP - 115 PB - Springer Nature CY - Cham ER - TY - JOUR A1 - Oberländer, Jan A1 - Kirchner, Patrick A1 - Keusgen, Michael A1 - Schöning, Michael Josef T1 - Strategies in developing thin-film sensors for monitoring aseptic food processes : Theoretical considerations and investigations of passivation materials JF - Electrochimica Acta N2 - The sterilization of packages in aseptic food processes is highly significant to maintain a consumer-safe product with extended shelf-life. Today, the sterilization of food packages is predominantly accomplished by gaseous hydrogen peroxide (H2O2) in combination with heat. In order to monitor this sterilization process, calorimetric gas sensors as differential set-up of two platinum temperature sensors representing a catalytically active (additionally deposition of MnO2) and a passive segment have been recently developed. The temperature rise of the exothermic decomposition serves as an indicator of the present H2O2 concentration. In the present work, a theoretical approach considering the sensor’s thermochemistry and physical transport phenomena was formulated to evaluate the temperature rise based on the energy content of gaseous H2O2. In a further part of this work, three polymers have been analyzed with respect to their application as passivation materials. The examined polymers are photoresist SU-8, perfluoroalkoxy (PFA) and fluorinated ethylene propylene (FEP). Thermal analyses by means of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) have been conducted to determine the operation limits of the polymers. The overall chemical resistance and stability of the polymers against the harsh environmental conditions during the sterilization process have been examined by attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Y1 - 2015 U6 - https://doi.org/10.1016/j.electacta.2015.06.126 SN - 0013-4686 VL - 183 SP - 130 EP - 136 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Miyamato, Ko-ichiro A1 - Sakakita, Sakura A1 - Wagner, Torsten A1 - Schöning, Michael Josef A1 - Yoshinobu, Tatsuo T1 - Application of chemical imaging sensor to in-situ pH imaging in the vicinity of a corroding metal surface JF - Electrochimica Acta N2 - The chemical imaging sensor was applied to in-situ pH imaging of the solution in the vicinity of a corroding surface of stainless steel under potentiostatic polarization. A test piece of polished stainless steel was placed on the sensing surface leaving a narrow gap filled with artificial seawater and the stainless steel was corroded under polarization. The pH images obtained during polarization showed correspondence between the region of lower pH and the site of corrosion. It was also found that the pH value in the gap became as low as 2 by polarization, which triggered corrosion. Y1 - 2015 U6 - https://doi.org/10.1016/j.electacta.2015.07.184 SN - 0013-4686 VL - 183 SP - 137 EP - 142 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Hamad, E. M. A1 - Bilatto, S. E. R. A1 - Adly, N. Y. A1 - Correa, D. S. A1 - Wolfrum, B. A1 - Schöning, Michael Josef A1 - Offenhäusser, A. A1 - Yakushenko, A. T1 - Inkjet printing of UV-curable adhesive and dielectric inks for microfluidic devices JF - Lab on a Chip N2 - Bonding of polymer-based microfluidics to polymer substrates still poses a challenge for Lab-On-a-Chip applications. Especially, when sensing elements are incorporated, patterned deposition of adhesives with curing at ambient conditions is required. Here, we demonstrate a fabrication method for fully printed microfluidic systems with sensing elements using inkjet and stereolithographic 3D-printing. Y1 - 2016 U6 - https://doi.org/10.1039/C5LC01195G SN - 1473-0189 VL - 16 IS - 1 SP - 70 EP - 74 PB - Royal Society of Chemistry CY - Cambridge ER - TY - JOUR A1 - Fischer, Felix A1 - Selver, M. Alper A1 - Gezer, Sinem A1 - Dicle, Oguz A1 - Hillen, Walter T1 - Systematic Parameterization, Storage, and Representation of Volumetric DICOM Data JF - Journal of Medical and Biological Engineering Y1 - 2015 U6 - https://doi.org/10.1007/s40846-015-0097-5 SN - 2199-4757 VL - 35 IS - 6 SP - 709 EP - 723 PB - Springer CY - Berlin ER - TY - JOUR A1 - Bayon, Arnau A1 - Valero, Daniel A1 - Garcia-Bartual, Rafael A1 - Vallés-Morán, Francisco José A1 - López-Jiménez, P. Amparo T1 - Performance assessment of OpenFOAM and FLOW-3D in the numerical modeling of a low Reynolds number hydraulic jump JF - Environmental Modelling & Software N2 - A comparative performance analysis of the CFD platforms OpenFOAM and FLOW-3D is presented, focusing on a 3D swirling turbulent flow: a steady hydraulic jump at low Reynolds number. Turbulence is treated using RANS approach RNG k-ε. A Volume Of Fluid (VOF) method is used to track the air–water interface, consequently aeration is modeled using an Eulerian–Eulerian approach. Structured meshes of cubic elements are used to discretize the channel geometry. The numerical model accuracy is assessed comparing representative hydraulic jump variables (sequent depth ratio, roller length, mean velocity profiles, velocity decay or free surface profile) to experimental data. The model results are also compared to previous studies to broaden the result validation. Both codes reproduced the phenomenon under study concurring with experimental data, although special care must be taken when swirling flows occur. Both models can be used to reproduce the hydraulic performance of energy dissipation structures at low Reynolds numbers. Y1 - 2016 SN - 1364-8152 U6 - https://doi.org/10.1016/j.envsoft.2016.02.018 VL - 80 SP - 322 EP - 335 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Dantism, Shahriar A1 - Takenaga, Shoko A1 - Wagner, Patrick A1 - Wagner, Torsten A1 - Schöning, Michael Josef T1 - Determination of the extracellular acidification of Escherichia coli K12 with a multi-​chamber-​based LAPS system JF - Physica status solidi (a) N2 - On-line monitoring of the metabolic activity of microorganisms involved in intermediate stages of biogas production plays an important role to avoid undesirable “down times” during the biogas production. In order to control this process, an on-chip differential measuring system based on the light-addressable potentiometric sensor (LAPS) principle combined with a 3D-printed multi-chamber structure has been realized. As a test microorganism, Escherichia coli K12 (E. coli K12) were used for cell-based measurements. Multi-chamber structures were developed to determine the metabolic activity of E. coli K12 in suspension for a different number of cells, responding to the addition of a constant or variable amount of glucose concentrations, enabling differential and simultaneous measurements. Y1 - 2016 U6 - https://doi.org/10.1002/pssa.201533043 SN - 1862-6300 VL - 213 IS - 6 SP - 1479 EP - 1485 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Breuer, Lars A1 - Raue, Markus A1 - Strobel, M. A1 - Mang, Thomas A1 - Schöning, Michael Josef A1 - Thoelen, R. A1 - Wagner, Torsten T1 - Hydrogels with incorporated graphene oxide as light-addressable actuator materials for cell culture environments in lab-on-chip systems JF - Physica status solidi (a) N2 - Abstractauthoren Graphene oxide (GO) nanoparticles were incorporated in temperature-sensitive Poly(N-isopropylacrylamide) (PNIPAAm) hydrogels. The nanoparticles increase the light absorption and convert light energy into heat efficiently. Thus, the hydrogels with GO can be stimulated spatially resolved by illumination as it was demonstrated by IR thermography. The temporal progression of the temperature maximum was detected for different concentrations of GO within the polymer network. Furthermore, the compatibility of PNIPAAm hydrogels with GO and cell cultures was investigated. For this purpose, culture medium was incubated with hydrogels containing GO and the viability and morphology of chinese hamster ovary (CHO) cells was examined after several days of culturing in presence of this medium. Y1 - 2016 U6 - https://doi.org/10.1002/pssa.201533056 SN - 1862-6300 VL - 213 IS - 6 SP - 1520 EP - 1525 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Pookhalil, Ali A1 - Amoabediny, Ghassem A1 - Tabesh, Hadi A1 - Behbahani, Mehdi A1 - Mottaghy, Khosrow T1 - A new approach for semiempirical modeling of mechanical blood trauma JF - The international journal of artificial organs N2 - Purpose Two semi-empirical models were recently published, both making use of existing literature data, but each taking into account different physical phenomena that trigger hemolysis. In the first model, hemoglobin (Hb) release is described as a permeation procedure across the membrane, assuming a shear stress-dependent process (sublethal model). The second model only accounts for hemoglobin release that is caused by cell membrane breakdown, which occurs when red blood cells (RBC) undergo mechanically induced shearing for a period longer than the threshold time (nonuniform threshold model). In this paper, we introduce a model that considers the hemolysis generated by both these possible phenomena. Methods Since hemolysis can possibly be caused by permeation of hemoglobin through the RBC functional membrane as well as by release of hemoglobin from RBC membrane breakdown, our proposed model combines both these models. An experimental setup consisting of a Couette device was utilized for validation of our proposed model. Results A comparison is presented between the damage index (DI) predicted by the proposed model vs. the sublethal model vs. the nonthreshold model and experimental datasets. This comparison covers a wide range of shear stress for both human and porcine blood. An appropriate agreement between the measured DI and the DI predicted by the present model was obtained. Conclusions The semiempirical hemolysis model introduced in this paper aims for significantly enhanced conformity with experimental data. Two phenomenological outcomes become possible with the proposed approach: an estimation of the average time after which cell membrane breakdown occurs under the applied conditions, and a prediction of the ratio between the phenomena involved in hemolysis. Y1 - 2016 U6 - https://doi.org/10.5301/ijao.5000474 SN - 1724-6040 VL - 39 IS - 4 SP - 171 EP - 177 PB - Sage CY - London ER - TY - JOUR A1 - Bertz, Morten A1 - Schöning, Michael Josef A1 - Molinnus, Denise A1 - Homma, Takayuki T1 - Influence of temperature, light, and H₂O₂ concentration on microbial spore inactivation: in-situ Raman spectroscopy combined with optical trapping JF - Physica status solidi (a) applications and materials science N2 - To gain insight on chemical sterilization processes, the influence of temperature (up to 70 °C), intense green light, and hydrogen peroxide (H₂O₂) concentration (up to 30% in aqueous solution) on microbial spore inactivation is evaluated by in-situ Raman spectroscopy with an optical trap. Bacillus atrophaeus is utilized as a model organism. Individual spores are isolated and their chemical makeup is monitored under dynamically changing conditions (temperature, light, and H₂O₂ concentration) to mimic industrially relevant process parameters for sterilization in the field of aseptic food processing. While isolated spores in water are highly stable, even at elevated temperatures of 70 °C, exposure to H₂O₂ leads to a loss of spore integrity characterized by the release of the key spore biomarker dipicolinic acid (DPA) in a concentration-dependent manner, which indicates damage to the inner membrane of the spore. Intensive light or heat, both of which accelerate the decomposition of H₂O₂ into reactive oxygen species (ROS), drastically shorten the spore lifetime, suggesting the formation of ROS as a rate-limiting step during sterilization. It is concluded that Raman spectroscopy can deliver mechanistic insight into the mode of action of H₂O₂-based sterilization and reveal the individual contributions of different sterilization methods acting in tandem. KW - hydrogen peroxide KW - optical spore trapping KW - Raman spectroscopy KW - sterilization conditions KW - temperature Y1 - 2024 U6 - https://doi.org/10.1002/pssa.202300866 SN - 1862-6319 (Online) SN - 1862-6300 (Print) N1 - Corresponding author: Michael J. Schöning IS - Early View PB - Wiley-VCH CY - Berlin ER - TY - JOUR A1 - Schoenrock, Britt A1 - Muckelt, Paul E. A1 - Hastermann, Maria A1 - Albracht, Kirsten A1 - MacGregor, Robert A1 - Martin, David A1 - Gunga, Hans-Christian A1 - Salanova, Michele A1 - Stokes, Maria J. A1 - Warner, Martin B. A1 - Blottner, Dieter T1 - Muscle stiffness indicating mission crew health in space JF - Scientific Reports N2 - Muscle function is compromised by gravitational unloading in space affecting overall musculoskeletal health. Astronauts perform daily exercise programmes to mitigate these effects but knowing which muscles to target would optimise effectiveness. Accurate inflight assessment to inform exercise programmes is critical due to lack of technologies suitable for spaceflight. Changes in mechanical properties indicate muscle health status and can be measured rapidly and non-invasively using novel technology. A hand-held MyotonPRO device enabled monitoring of muscle health for the first time in spaceflight (> 180 days). Greater/maintained stiffness indicated countermeasures were effective. Tissue stiffness was preserved in the majority of muscles (neck, shoulder, back, thigh) but Tibialis Anterior (foot lever muscle) stiffness decreased inflight vs. preflight (p < 0.0001; mean difference 149 N/m) in all 12 crewmembers. The calf muscles showed opposing effects, Gastrocnemius increasing in stiffness Soleus decreasing. Selective stiffness decrements indicate lack of preservation despite daily inflight countermeasures. This calls for more targeted exercises for lower leg muscles with vital roles as ankle joint stabilizers and in gait. Muscle stiffness is a digital biomarker for risk monitoring during future planetary explorations (Moon, Mars), for healthcare management in challenging environments or clinical disorders in people on Earth, to enable effective tailored exercise programmes. KW - Ageing KW - Anatomy KW - Muscle KW - Musculoskeletal system KW - Physiology Y1 - 2024 U6 - https://doi.org/10.1038/s41598-024-54759-6 SN - 2045-2322 N1 - Corresponding author: Dieter Blottner VL - 14 IS - Article number: 4196 PB - Springer Nature CY - London ER -