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Year of publication
Institute
- Fachbereich Chemie und Biotechnologie (472) (remove)
Language
- English (472) (remove)
Document Type
- Article (472) (remove)
Keywords
- Heparin (3)
- Bacillaceae (2)
- Biotechnological application (2)
- Butanol (2)
- Chemometrics (2)
- IR spectroscopy (2)
- NMR spectroscopy (2)
- Principal component analysis (2)
- Standardization (2)
- Subtilases (2)
Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
Oosterhuis, Koen ; Öhlschläger, Peter ; Berg, Joost H. van den ; Toebes, Mireille ; Gomez, Raquel ; Schumacher, Ton N. ; Haanen, John B.
Henken, F. E. ; Oosterhuis, K. ; Öhlschläger, Peter ; Bosch, L. ; Hooijberg, E. ; Haanen, J. B. A. G. ; Steenbergen, R. D. M.
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.
We present the production of 58mCo on a small, 13 MeV medical cyclotron utilizing a siphon style liquid target system. Different concentrated iron(III)-nitrate solutions of natural isotopic distribution were irradiated at varying initial pressures and subsequently separated by solid phase extraction chromatography. The radio cobalt (58m/gCo and 56Co) was successfully produced with saturation activities of (0.35 ± 0.03) MBq μA−1 for 58mCo with a separation recovery of (75 ± 2) % of cobalt after one separation step utilizing LN-resin.
Production of Y-86 and other radiometals for research purposes using a solution target system
(2015)
Paulßen, Elisabeth ; Hoehr, Cornelia ; Hou, Xinchi ; Hanemaayer, Victoire ; Zeisler, Stefan ; Adam, Michael J. ; Ruth, Thomas J. ; Celler, Anna ; Buckley, Ken ; Benard, Francois ; Schaffer, Paul
Dellmann, Sophia Florence ; Glorius, J. ; Litvinov, Yu A. ; Reifarth, R. ; Al-Khasawneh, Kafa ; Aliotta, M. ; Bott, L. ; Brückner, Benjamin ; Bruno, C. G. ; Chen, Ruijiu ; Davinson, T. ; Dickel, T. ; Dillmann, Iris ; Dmytriev, D. ; Erbacher, P. ; Freire-Fernández, D. ; Forstner, Oliver ; Geissel, H. ; Göbel, K. ; Griffin, Christopher J. ; Grisenti, R. ; Gumberidze, Alexandre ; Haettner, Emma ; Hagmann, Siegbert ; Heil, M. ; Heß, R. ; Hillenbrand, P.-M. ; Joseph, R. ; Jurado, B. ; Kozhuharov, Christophor ; Kulikov, I. ; Löher, Bastian ; Langer, Christoph ; Leckenby, Guy ; Lederer-Woods, C. ; Lestinsky, M. ; Litvinov, S. A. ; Lorenz, B. A. ; Lorenz, E. ; Marsh, J. ; Menz, Esther Babette ; Morgenroth, T. ; Petridis, N. ; Pibernat, Jerome ; Popp, U. ; Psaltis, Athanasios ; Sanjari, Shahab ; Scheidenberger, C. ; Sguazzin, M. ; Sidhu, Ragandeep Singh ; Spillmann, Uwe ; Steck, M. ; Stöhlker, T. ; Surzhykov, A. ; Swartz, J. A. ; Törnqvist, H. ; Varga, L. ; Vescovi, Diego ; Weick, H. ; Weigand, M. ; Woods, P. ; Xing, Y. ; Yamaguchi, Taiyo
Experimental determination of the cross sections of proton capture on radioactive nuclei is extremely difficult. Therefore, it is of substantial interest for the understanding of the production of the p-nuclei. For the first time, a direct measurement of proton-capture cross sections on stored, radioactive ions became possible in an energy range of interest for nuclear astrophysics. The experiment was performed at the Experimental Storage Ring (ESR) at GSI by making use of a sensitive method to measure (p,γ) and (p,n) reactions in inverse kinematics. These reaction channels are of high relevance for the nucleosyn-thesis processes in supernovae, which are among the most violent explosions in the universe and are not yet well understood. The cross section of the ¹¹⁸Te(p,γ) reaction has been measured at energies of 6 MeV/u and 7 MeV/u. The heavy ions interacted with a hydrogen gas jet target. The radiative recombination process of the fully stripped ¹¹⁸Te ions and electrons from the hydrogen target was used as a luminosity monitor. An overview of the experimental method and preliminary results from the ongoing analysis will be presented.
In traditional microbial biobutanol production, the solvent must be recovered during fermentation process for a sufficient space-time yield. Thermal separation is not feasible due to the boiling point of n-butanol. As an integrated and selective solid-liquid separation alternative, solvent impregnated resins (SIRs) were applied. Two polymeric resins were evaluated and an extractant screening was conducted. Vacuum application with vapor collection in fixed-bed column as bioreactor bypass was successfully implemented as butanol desorption step. In course of further increasing process economics, fermentation with renewable lignocellulosic substrates was conducted using Clostridium acetobutylicum. Utilization of SIR was shown to be a potential strategy for solvent removal from fermentation broth, while application of a bypass column allows for product removal and recovery at once.
Hasegawa, Maki ; Kapelyukh, Yury ; Tahara, Harunobu ; Seibler, Jost ; Rode, Anja ; Krueger, Sylvia ; Lee, Dongtao N. ; Wolf, C. Roland ; Scheer, Nico
Monakhova, Yulia ; Soboleva, Polina M. ; Fedotova, Elena S. ; Musina, Kristina T. ; Burmistrova, Natalia A.
Heparin is a natural polysaccharide, which plays essential role in many biological processes. Alterations in building blocks can modify biological roles of commercial heparin products, due to significant changes in the conformation of the polymer chain. The variability structure of heparin leads to difficulty in quality control using different analytical methods, including infrared (IR) spectroscopy. In this paper molecular modelling of heparin disaccharide subunits was performed using quantum chemistry. The structural and spectral parameters of these disaccharides have been calculated using RHF/6-311G. In addition, over-sulphated chondroitin sulphate disaccharide was studied as one of the most widespread contaminants of heparin. Calculated IR spectra were analyzed with respect to specific structure parameters. IR spectroscopic fingerprint was found to be sensitive to substitution pattern of disaccharide subunits. Vibrational assignments of calculated spectra were correlated with experimental IR spectral bands of native heparin. Chemometrics was used to perform multivariate analysis of simulated spectral data.