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Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
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.
Preprint: Studies on the enzymatic reduction of levulinic acid using Chiralidon-R and Chiralidon-S
(2023)
The enzymatic reduction of levulinic acid by the chiral catalysts Chiralidon-R and Chiralidon-S which are commercially available superabsorbed alcohol dehydrogenases is described. The Chiralidon®-R/S reduces the levulinic acid to the (R,S)-4-hydroxy valeric acid and the (R)- or (S)- gamma-valerolactone.
Production of Y-86 and other radiometals for research purposes using a solution target system
(2015)
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.
Ein viel versprechender erneuerbarer Rohstoff für die Produktion von Chemikalien und Treibstoffen ist Lignocellulose aus pflanzlicher Biomasse. Die darin enthaltenen Zucker können 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.
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.
Quaternary events at the Horn of Africa / Voigt, B., B. Gabriel, B. Lassonczyk and Mumin M. Ghod
(1990)
Oxorhenium(V) complexes [ReOX3(PPh3)2] (X = Cl, Br) react with phenylacetylene under formation of complexes with ylide-type ligands. Compounds of the compositions [ReOCl3(PPh3){C(Ph)C(H)(PPh3)}] (1), [ReOBr3(OPPh3){C(Ph)C(H)(PPh3)}] (2), and [ReOBr3(OPPh3){C(H)C(Ph)(PPh3)}] (3) were isolated and characterized by X-ray diffraction. They contain a ligand, which was formed by a nucleophilic attack of released PPh3 at coordinated phenylacetylene. The structures of the products show that there is no preferable position for this attack. Cleavage of the Re–C bond in 3 and dimerization of the organic ligand resulted in the formation of the [{(PPh3)(H)CC(Ph)}2]2+ cation, which crystallized as its [(ReOBr4)(OReO3)]2– salt.
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.
Die Erfindung betrifft eine schwefelvernetzbare Kautschukmischung, deren Vulkanisat und einen Fahrzeugreifen. Die erfindungsgemäße Kautschukmischung enthält wenigstens folgende Bestandteile: - Wenigstens einen Dienkautschuk; - wenigstens eine Kohle (HTC-Kohle), die mittels hydrothermaler Karbonisierung von wenigstens einer Ausgangssubstanz hergestellt ist. Der erfindungsgemäße Fahrzeugreifen weist in wenigstens einem Bauteil wenigstens ein erfindungsgemäßes Vulkanisat der Kautschukmischung auf.
Die Erfindung betrifft eine schwefelvernetzbare Kautschukmischung, deren Vulkanisat und einen Fahrzeugreifen. Die schwefelvernetzbare Kautschukmischung enthält wenigstens die folgenden Bestandteile: - wenigstens einen Dienkautschuk; und - 10 bis 300 phr wenigstens einer Kieselsäure; und - 1 bis 30 phf wenigstens eines Silans A mit der allgemeinen Summenformel A-I) A-I)(R1)oSi-R2-(S-R3)q-S-X; und - 0,5 bis 30 phf wenigstens eines Silans B mit der allgemeinen Summenformel B-I) B-I) (R1)oSi-R2-(S-R3)u-S-R2-Si(R1)o wobei q =1, 2 oder 3 ist; und u = 1, 2 oder 3 ist; und X ein Wasserstoffatom oder eine –C(=O)-R8 Gruppe ist wobei R8 ausgewählt ist aus Wasserstoff, C1-C20 Alkylgruppen, vorzugsweise C1-C17, C6-C20- Arylgruppen, vorzugsweise Phenyl, C2-C20-Alkenylgruppen und C7-C20-Aralkylgruppen.
Die Erfindung betrifft eine schwefelvernetzbare Kautschukmischung, deren Vulkanisat und einen Fahrzeugreifen.Die schwefelvernetzbare Kautschukmischung enthält wenigstens die folgenden Bestandteile:- wenigstens einen Dienkautschuk; und- 10 bis 300 phr wenigstens einer Kieselsäure ; und- 1 bis 30 phf wenigstens eines Silans A mit der allgemeinen Summenformel A-I)und- 0,5 bis 30 phf wenigstens eines Silans B mit der allgemeinen Summenformel B-I)wobei u gleich 0, 1, 2 oder 3 und v gleich 0 oder 1 ist.
Sekundäre galvanische Zelle
(2020)
Die vorliegende Erfindung betrifft eine sekundäre galvanische Zelle, umfassend eine Kathode, eine Anode und einen Separator, der zwischen der Kathode und der Anode angeordnet ist, wobei die Kathode ein erstes elastomeres Polymer umfasst, welches mit einem ersten Füllstoff als Kathodenmaterial gefüllt ist, wobei die Anode ein zweites elastomeres Polymer umfasst, welches mit einem zweiten Füllstoff als Anodenmaterial gefüllt ist, wobei der Separator ein drittes elastomeres Polymer umfasst, wobei das erste elastomere Polymer, das zweite elastomere Polymer und das dritte elastomere Polymer unabhängig voneinander aus vernetzungsfähigen Dienkautschuken ausgewählt sind, und wobei zumindest eines von dem ersten elastomeren Polymer, dem zweiten elastomeren Polymer und dem dritten elastomeren Polymer eine ionische Flüssigkeit und/oder ein elektrisch leitfähiges Polymer enthält. Die vorliegende Erfindung betrifft ferner eine wiederaufladbare Batterie, umfassend die erfindungsgemäße sekundäre galvanische Zelle, ein Verfahren zur Herstellung einer sekundären galvanischen Zelle sowie die Verwendung der erfindungsgemäßen sekundären galvanischen Zelle sowie der erfindungsgemäßen wiederaufladbaren Batterie.
In Anbetracht des zu erwartenden Rückgangs der Verfügbarkeit fossiler Rohstoffe müssen nicht nur für den Energiesektor, sondern auch für die Herstellung industrieller Produkte alternative Rohstoffe gefunden werden. Ein Beispiel für einen nicht in Nahrungsmittelkonkurrenz stehenden nachwachsenden Rohstoff ist grüne Biomasse wie Gras und Klee. Diese lassen sich in Deutschland auf großen Flächen anbauen und enthalten eine Vielzahl potenzieller Substrate für Fermentationen.
In this study, a recently proposed NMR standardization approach by 2H integral of deuterated solvent for quantitative multicomponent analysis of complex mixtures is presented. As a proof of principle, the existing NMR routine for the analysis of Aloe vera products was modified. Instead of using absolute integrals of targeted compounds and internal standard (nicotinamide) from 1H-NMR spectra, quantification was performed based on the ratio of a particular 1H-NMR compound integral and 2H-NMR signal of deuterated solvent D2O. Validation characteristics (linearity, repeatability, accuracy) were evaluated and the results showed that the method has the same precision as internal standardization in case of multicomponent screening. Moreover, a dehydration process by freeze drying is not necessary for the new routine. Now, our NMR profiling of A. vera products needs only limited sample preparation and data processing. The new standardization methodology provides an appealing alternative for multicomponent NMR screening. In general, this novel approach, using standardization by 2H integral, benefits from reduced sample preparation steps and uncertainties, and is recommended in different application areas (purity determination, forensics, pharmaceutical analysis, etc.).
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.
Simultane Atline-Quantifizierung von Magnetpartikeln und Mikroorganismen bei einer HGMS-Filtration
(2015)
Es wird eine neue Atline-Messmethode vorgestellt, mit der während einer Hochgradienten-Magnetseparation (HGMS)-Filtration eine simultane Quantifizierung von Magnetpartikeln und Mikroorganismen im Filtrat vorgenommen werden kann. Dabei gelingt die Quantifizierung signifikant besser als mit bisher verwendeten Messmethoden. Mit dieser Methode ist es möglich, die Trennleistung einer HGMS-Filtration zu bestimmen und einen Filterdurchbruch durch Konzentrationsanstiege im Bereich einiger µg L−1 von Magnetpartikeln im Filtrat frühzeitig zu detektieren, ohne dass nennenswerte Partikelmengen verloren gehen.