Negative Kostimulation zur Verhinderung der humanen T-Zellreaktivität gegen porzines Xenoantigen

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Ubiquitous LEA29Y Expression Blocks T Cell Co-Stimulation but Permits Sexual Reproduction in Genetically Modified Pigs

We have successfully established and characterized a genetically modified pig line with ubiquitous expression of LEA29Y, a human CTLA4-Ig derivate. LEA29Y binds human B7.1/CD80 and B7.2/CD86 with high affinity and is thus a potent inhibitor of T cell co-stimulation via this pathway. We have characterized the expression pattern and the biological function of the transgene as well as its impact on the porcine immune system and have evaluated the potential of these transgenic pigs to propagate via assisted breeding methods. The analysis of LEA29Y expression in serum and multiple organs of CAG-LEA transgenic pigs revealed that these animals produce a biologically active transgenic product at a considerable level. They present with an immune system affected by transgene expression, but can be maintained until sexual maturity and propagated by assisted reproduction techniques. Based on previous experience with pancreatic islets expressing LEA29Y, tissues from CAG-LEA29Y transgenic pigs should be protected against rejection by human T cells. Furthermore, their immune-compromised phenotype makes CAG-LEA29Y transgenic pigs an interesting large animal model for testing human cell therapies and will provide an important tool for further clarifying the LEA29Y mode of action

Werkstoffkundliche und verfahrenstechnische Untersuchungen zum Laserstrahlschweissen von hochfesten Aluminiumlegierungen Abschlussbericht zum Teilvorhaben des BMFT-Verbundprojektes ''Fuegen mit CO_2-Hochleistungslasern''

Within the framework of the documented research project, the aviation alloys 2024, 7475, 2090, 2091 and 8090 were investigated for their welding properties within the thickness range from 1 mm to 2.5 mm by means of a CW-CO_2 laser of the 4 kW power class. All weldings were made without using any filler alloys, mainly as square butt joints, but also as lap seams. It is shown that with an appropriate selection of power density and feed it was possible to weld all alloys securely, with the exception of 2024 for which the welding process remained unstable even after optimization of all boundary parameters. For all alloys careful chemical and mechanical pretreatment of the edges to be welded proved important to obtaining reproducible and low pore weldings. In addition, great importance is attributed to gas flow control. The mechanical properties of sample weldings were investigated for various combinations of welding processes and heat treatment. After welding in a cold or hot aged condition, between 50% and 80% of the strength of the basic alloy were obtained with elongations of a few percent. (orig./RHM)SIGLEAvailable from TIB Hannover: F94B0223+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Trennen mit Festkoerperlasern. Teilvorhaben: Werkstoffkundliche- und Prozessuntersuchungen zum Schneiden von Blechbauteilen aus hochfesten Titan- und Aluminiumlegierungen sowie Maskierungen Abschlussbericht

The primary objective of the project documented here was to optimize the process technology of cutting titanium and aluminum alloys with pulsed solid-state lasers of good beam quality and to characterize the results achievable by means of the optimized cutting conditions in terms of materials science. As the investigations presented here have shown, cutting of aluminum and titanium aviation alloys by means of pulsed solid-state lasers - even after optimization of all process parameters - initially has the disadvantages of high edge roughness, relatively poor expulsion of the melt, and for some aluminum alloys, inevitable microcrack initiation on the cut edges. With proper selection of the overall machining sequence of laser cutting, grinding or chemical ablation as well as heat treatment, pulsed solid-state lasers of high beam quality, however, can be used for cutting of age-hardenable aluminum alloys and titanium alloys without any quality problems. In all cases, static strength, fatigue behavior and corrosive properties similar to those of milled edges can be achieved. Therefore, these lasers can be used in the development and small series production of aviation industry as a very economic and efficiency enhancing alternative to the traditional, manually or NC-controlled contour machining by milling. (orig./RHM)Available from TIB Hannover: F95B76 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman