Uptake of IgG in osteosarcoma correlates inversely with interstitial fluid pressure, but not with interstitial constituents

The uptake of therapeutic macromolecules in solid tumours is assumed to be hindered by the heterogeneous vascular network, the high interstitial fluid pressure, and the extracellular matrix. To study the impact of these factors, we measured the uptake of fluorochrome-labelled IgG using confocal laser scanning microscopy, interstitial fluid pressure by the ‘wick-in-needle’ technique, vascular structure by stereological analysis, and the content of the extracellular matrix constituents collagen, sulfated glycosaminoglycans and hyaluronan by colourimetric assays. The impact of the microenvironment on these factors was studied using osteosarcomas implanted either subcutaneously or orthotopically around the femur in athymic mice. The uptake of IgG was found to correlate inversely with the interstitial fluid pressure and the tumour volume in orthotopic, but not subcutaneous tumours. No correlation was found between IgG uptake and the level of any of the extracellular matrix constituents. The content of both collagen and glycosaminoglycans depended on the site of tumour growth. The orthotopic tumours had a higher vascular density than the subcutaneous tumours, as the vascular surface and length were 2–3-fold higher. The data indicate that the interstitial fluid pressure is a dominant factor in controlling the uptake of macromolecules in solid tumours; and the site of tumour growth is important for the uptake of macromolecules in small tumours, extracellular matrix content and vascularization.© 2001 Cancer Research Campaign http://www.bjcancer.co

Statistical fault diagnosis of wind turbine drivetrain applied to a 5MW floating wind turbine

Deployment of large scale wind turbine parks, in particular offshore, requires well organized operation and maintenance strategies to make it as competitive as the classical electric power stations. It is important to ensure systems are safe, profitable, and cost-effective. In this regards, the ability to detect, isolate, estimate, and prognose faults plays an important role. One of the critical wind turbine components is the gearbox. Failures in the gearbox are costly both due to the cost of the gearbox itself and also due to high repair downtime. In order to detect faults as fast as possible to prevent them to develop into failure, statistical change detection is used in this paper. The Cumulative Sum Method (CUSUM) is employed to detect possible defects in the downwind main bearing. A high fidelity gearbox model on a 5-MW spar-type wind turbine is used to generate data for fault-free and faulty conditions of the bearing at the rated wind speed and the associated wave condition. Acceleration measurements are utilized to find residuals used to indirectly detect damages in the bearing. Residuals are found to be nonGaussian, following a t-distribution with multivariable characteristic parameters. The results in this paper show how the diagnostic scheme can detect change with desired false alarm and detection probabilities.<br/