Human monoclonal antibodies to domain C of tenascin-C selectively target solid tumors in vivo

We had previously reported that splice isoforms of tenascin-C containing the extra-domain C are virtually absent in normal adult tissues but are highly abundant in high-grade astrocytomas, with a prominent peri-vascular pattern of expression. We now report that the extra-domain C of tenascin-C is strongly expressed in the majority of lung cancers, with a vascular and stromal pattern of expression. Using antibody phage technology, we have generated a human monoclonal antibody (G11), with a dissociation constant K(D) = 4.2 nM for the human domain C. The G11 antibody, expressed in scFv and in mini-antibody (SIP) format, as well as a scFv-interleukin-2 fusion protein, was then characterized in quantitative biodistribution studies using mice grafted subcutaneously with U87 gliomas, revealing a selective tumor uptake, with tumor/blood ratios up to 11.8:1 at 24 h. A radioiodinated preparation of SIP(G11) was also investigated in a double tracer study using an orthotopic rat glioma model, confirming the antibody's ability to preferentially localize at the tumor site, with tumor/brain ratios superior to the ones observed with (18)F-fluorodeoxyglucose. These tumor-targeting properties, together with the strong immunohistochemical staining of human tumor sections, indicate that the G11 antibody may be used as a portable targeting moiety for the selective delivery of imaging and therapeutic agents to gliomas and lung tumors.     

Using 3D-scanners and finite element method to assess the fatigue life of welded joints based on the actual geometry of seam welds: realistic modelling of notches at the weld toe

To predict the service life of welded joints, the seam welds of samples (cross joint, K-seam, sheet thickness 15 mm and a laser-welded butt joint, sheet thickness 6 mm, both made of steel quality S 355) are recorded using a 3D scanner. The data obtained in this way is processed and transferred to a finite element method program. The meshing of the weld seams is very detailed. A finite-element-method stress calculation is then carried out. The real samples are tested in a fatigue test up to the point of cracking. The results from calculation and test are then compared. A possible crack location can be predicted very well using the finite element method results. The cracks in the real test are always in the area of very high or often the absolute highest calculated stresses. A prediction of the service life in the fatigue test is possible with a certain scatter – close to the usual scatter for welded joints. Based on the results of 19 samples, a fatigue class for local stress (based on the real geometry) of FAT 300 can be preliminary estimated for the cross-joint specimens. Definition according to the specifications of the International Institute of Welding (FAT at 2 mio. cycles, survival probability 97.7 %).     

Untersuchungen zur Vergleichbarkeit der statischen und dynamischen Überdruckprüfung von druckfesten Kapselungen

Forschung im Ingenieurwesen - Der Einsatz von elektrischen Geräten in explosionsgefährdeten Bereichen erfordert besondere Schutzmaßnahmen, um eine Zündung der...