Otto Haesler und der Städtebau der DDR in den fünfziger Jahren

Wissenschaftliches Kolloquium vom 18. bis 21. Juni 1992 in Weimar an der Hochschule für Architektur und Bauwesen zum Thema: ‚Architektur und Macht

Ephrin-A5 Induces Collapse of Growth Cones by Activating Rho and Rho Kinase

The ephrins, ligands of Eph receptor tyrosine kinases, have been shown to act as repulsive guidance molecules and to induce collapse of neuronal growth cones. For the first time, we show that the ephrin-A5 collapse is mediated by activation of the small GTPase Rho and its downstream effector Rho kinase. In ephrin-A5–treated retinal ganglion cell cultures, Rho was activated and Rac was downregulated. Pretreatment of ganglion cell axons with C3-transferase, a specific inhibitor of the Rho GTPase, or with Y-27632, a specific inhibitor of the Rho kinase, strongly reduced the collapse rate of retinal growth cones. These results suggest that activation of Rho and its downstream effector Rho kinase are important elements of the ephrin-A5 signal transduction pathway

On explicit results at the intersection of the Z_2 and Z_4 orbifold subvarieties in K3 moduli space

We examine the recently found point of intersection between the Z_2 and Z_4 orbifold subvarieties in the K3 moduli space more closely. First we give an explicit identification of the coordinates of the respective Z_2 and Z_4 orbifold theories at this point. Secondly we construct the explicit identification of conformal field theories at this point and show the orthogonality of the two subvarieties.Comment: Latex, 23 page

Generation of human antibody fragments against Streptococcus mutans using a phage display chain shuffling approach

BACKGROUND: Common oral diseases and dental caries can be prevented effectively by passive immunization. In humans, passive immunotherapy may require the use of humanized or human antibodies to prevent adverse immune responses against murine epitopes. Therefore we generated human single chain and diabody antibody derivatives based on the binding characteristics of the murine monoclonal antibody Guy's 13. The murine form of this antibody has been used successfully to prevent Streptococcus mutans colonization and the development of dental caries in non-human primates, and to prevent bacterial colonization in human clinical trials. RESULTS: The antibody derivatives were generated using a chain-shuffling approach based on human antibody variable gene phage-display libraries. Like the parent antibody, these derivatives bound specifically to SAI/II, the surface adhesin of the oral pathogen S. mutans. CONCLUSIONS: Humanization of murine antibodies can be easily achieved using phage display libraries. The human antibody fragments bind the antigen as well as the causative agent of dental caries. In addition the human diabody derivative is capable of aggregating S. mutans in vitro, making it a useful candidate passive immunotherapeutic agent for oral diseases

Combined Pharmacological Inhibition of Cyclophilins, FK506-Binding Proteins, Hsp90, and Hsp70 Protects Cells From Clostridium botulinum C2 Toxin

The Clostridium botulinum C2 toxin is an exotoxin causing severe enterotoxic symptoms. The C2 toxin consists of the binding/translocation component C2II, and the enzymatic active component C2I. After proteolytic activation, C2IIa forms heptamers that bind C2I. The C2IIa/C2I complex is taken up into mammalian target cells via receptor-mediated endocytosis. Acidification of endosomes leads to conformational changes in both components. C2IIa heptamers form a pore into the endosomal membrane, and C2I becomes unfolded and translocates through the narrow C2IIa pores into the cytosol of the cell. Here, C2I covalently transfers an ADP-ribose moiety from its co-substrate NAD+ onto G-actin, which leads to depolymerization of F-actin resulting in rounding up of adherent cells. Translocation of C2I into the cytosol depends on the activity of the chaperones Hsp90 and Hsp70 and peptidyl-prolyl cis/trans isomerases of the cyclophilin (Cyp) and FK506-binding protein (FKBP) families. Here, we demonstrated that C2I is detected in close proximity with Hsp90, Cyp40, and FKBP51 in cells, indicating their interaction. This interaction was dependent on the concentration of C2 toxin and detected in mammalian Vero and human HeLa cells. Moreover, the present study reveals that combination of radicicol, VER-155008, cyclosporine A, and FK506, which are specific pharmacological inhibitors of Hsp90, Hsp70, Cyps, and FKBPs, respectively, resulted in a stronger inhibition of intoxication of cells with C2 toxin compared to application of the single inhibitors. Thus, the combination of inhibitors showed enhanced protection of cells against the cytotoxic effects of C2 toxin. Cell viability was not significantly impaired by application of the inhibitor combination. Moreover, we confirmed that the combination of radicicol, VER-155008, CsA, and FK506 in particular inhibit the membrane translocation step of C2I into the cytosol whereas receptor binding and enzyme activity of the toxin were not affected. Our findings further characterize the mode of action of Hsp90, Hsp70, Cyps, and FKBPs during membrane translocation of bacterial toxins and furthermore supply starting points for developing of novel therapeutic strategies against diseases caused by bacterial toxins that depend on Hsp90, Hsp70, Cyps, and FKBPs

Superconducting CH Cavities for Heavy Ion Acceleration

To demonstrate the operation ability of superconducting (sc) Crossbar-H-mode (CH) cavity technology a 217 MHz structure of this type is under development at the Institute for Applied Physics (IAP) of Frankfurt University. The cavity has 15 accelerating cells and a design beta of 0.059. It will be equipped with all necessary auxiliaries like a 10 kW power coupler and a tuning system. Currently, the cavity is under construction. Furthermore, this cavity will serve as demonstrator for a sc continuous wave (cw) LINAC at GSI. The proposed cw LINAC is highly requested to fulfil the requirements of nuclear chemistry and especially for a competitive production of new Super Heavy Elements (SHE) in the future. A full performance test by injecting and accelerating a beam from the GSI High Charge Injector (HLI) is planned in 2014. The current status of the sc CH cavity and the demonstrator project is presented