Receptor tyrosine kinases such as VEGFR2 (vascular endothelial growth factor receptor 2, KDR) or EGFR (epidermal growth factor receptor) play crucial roles in a variety of diseases, such as cancer. Recently, some pyrrolopyrimidines were shown to be potent EGFR inhibitors. Therefore, new types of oxazolo[5,4‐d]pyrimidines and furo[2,3‐d]pyrimidines were synthesized (Schemes 1 and 2). Appropriately substituted derivatives of these classes of compounds inhibited VEGFR2 and EGFR with IC50 values in the low nanomolar range (see Table). Generally, the furopyrimidines were somewhat more active than the oxazolopyrimidines. The best inhibitors, 20m, 20p , and 20r , had an IC50 of 3 nM towards EGFR and showed a good selectivity, being distinctly less active towards VEGFR2. 相似文献
We solve the asymptotic Plateau problem in every Gromov hyperbolic Hadamard manifold (X,g) with bounded geometry. That is, we prove existence of complete (possibly singular) k-dimensional area minimizing surfaces in X with prescribed boundary data at infinity, for a large class of admissible limit sets and for all . The result also holds with respect to any riemannian metric on X which is lipschitz equivalent to g.
Received: 23 January 2001 / Accepted: 25 October 2001 Published online: 28 February 2002 相似文献
A more thorough understanding of the properties of bulk material structures in solid–liquid separation processes is essential to understand better and optimize industrially established processes, such as cake filtration, whose process outcome is mainly dependent on the properties of the bulk material structure. Here, changes of bulk properties like porosity and permeability can originate from local variations in particle size, especially for non-spherical particles. In this study, we mix self-similar fractions of crushed, irregularly shaped Al2O3 particles (20 to 90 µm and 55 to 300 µm) to bimodal distributions. These mixtures vary in volume fraction of fines (0, 20, 30, 40, 50, 60 and 100 vol.%). The self-similarity of both systems serves the improved parameter correlation in the case of multimodal distributed particle systems. We use nondestructive 3D X-ray microscopy to capture the filter cake microstructure directly after mechanical dewatering, whereby we give particular attention to packing structure and particle–particle relationships (porosity, coordination number, particle size and corresponding hydraulic isolated liquid areas). Our results reveal widely varying distributions of local porosity and particle contact points. An average coordination number (here 5.84 to 6.04) is no longer a sufficient measure to describe the significant bulk porosity variation (in our case, 40 and 49%). Therefore, the explanation of the correlation is provided on a discrete particle level. While individual particles?<?90 µm had only two or three contacts, others?>?100 µm took up to 25. Due to this higher local coordination number, the liquid load of corresponding particles (liquid volume/particle volume) after mechanical dewatering increases from 0.48 to 1.47.
Journal of Optimization Theory and Applications - There is a significant tendency in the industry for automation of the engineering design process. This requires the capability of analyzing an... 相似文献
We present a miniature fiber-optic electromagnetic field (EMF) sensor that is capable of simultaneously detecting the amplitude and phase of an EMF in the range of 0.1-6 GHz. We focus on magnetic field measurements, since the H-field is more significant in our target applications due its direct relation to the current. The sensor is based on an open optical platform to which various antennas can be attached and contains a radio-frequency amplifier for signal conditioning and a vertical-cavity surface-emitting laser as an electro-optic converter. The millimeter size and the full electrical isolation of the sensor allow EMF detection with minimal disturbance. We have characterized the sensor in the near field of a lambda/2 dipole, a rectangular waveguide, and a microstrip line, and we explain the experimental results with a simple theoretical model confirming the mapped near-field distribution of the investigated field source. 相似文献
Stand-off technology for the remote detection of explosives and their traces on contaminated surfaces is a field of research that has recently gained much interest. Optical methods are well established in applications for counterterrorism because they facilitate analysis without contact between human being and hazardous materials. In this paper, to our knowledge for the first time, a remote stand-off detection system is developed by combination of pulsed laser fragmentation and pulsed mid-infrared laser absorption spectroscopy. Since the absorption of explosives is more efficient for infrared wavelengths laser radiation in the eye safe region around λ=1.47 μm rather than the conventional Nd:YAG laser line at λ=1.06 μm is preferred for the fragmentation. Generated product gases such as nitric oxide are probed by a synchronized distributed feedback quantum cascade laser (DFB-QCL) at λ≈5.3 μm. The ratio of NO and NO2 is a measure to distinguish between energetic and non-energetic materials. PACS 42.62.Fi; 07.07.DF; 42.55.Px 相似文献