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Pressen - Vergleich zwischen Raumlenker- und Exzenterantrieb / Doege, Eckhart ; Engels, Elmar
(1999)
Pressen - Hubzahlregelung an Schnelläuferpressen mit Fuzzy-Reglern / Doege, Eckhart ; Engels, Elmar
(1998)
We are developing an X-ray computed tomography (CT) system which will be combined with a high resolution animal PET system. This permits acquisition of both molecular and anatomical images in a single machine. In particular the CT will also be utilized for the quantification of the animal PET data by providing accurate data for attenuation correction. A first prototype has been built using a commercially available plane silicon diode detector. A cone-beam reconstruction provides the images using the Feldkamp algorithm. First measurements with this system have been performed on a mouse. It could be shown that the CT setup fulfils all demands for a high quality image of the skeleton of the mouse. It is also suited for soft tissue measurements. To improve contrast and resolution and to acquire the X-ray energy further development of the system, especially the use of semiconductor detectors and iterative reconstruction algorithms are planned.
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.
Preclinical development of highly effective and safe DNA vaccines directed against HPV 16 E6 and E7
(2011)
This study describes the development of a new combined polysaccharide-matrix-based technology for the immobilization of Lactobacillus rhamnosus GG (LGG) bacteria in biofilm form. The new composition allows for delivering the bacteria to the digestive tract in a manner that improves their robustness compared with planktonic cells and released biofilm cells. Granules consisting of a polysaccharide matrix with probiotic biofilms (PMPB) with high cell density (>9 log CFU/g) were obtained by immobilization in the optimized nutrient medium. Successful probiotic loading was confirmed by fluorescence microscopy and scanning electron microscopy. The developed prebiotic polysaccharide matrix significantly enhanced LGG viability under acidic (pH 2.0) and bile salt (0.3%) stress conditions. Enzymatic extract of feces, mimicking colon fluid in terms of cellulase activity, was used to evaluate the intestinal release of probiotics. PMPB granules showed the ability to gradually release a large number of viable LGG cells in the model colon fluid. In vivo, the oral administration of PMPB granules in rats resulted in the successful release of probiotics in the colon environment. The biofilm-forming incubation method of immobilization on a complex polysaccharide matrix tested in this study has shown high efficacy and promising potential for the development of innovative biotechnologies.