Furo[2,3‐d]pyrimidines and Oxazolo[5,4‐d]pyrimidines as Inhibitors of Receptor Tyrosine Kinases (RTK)

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.     

Asynchronous two-stage iterative methods

Summary. Parallel block two-stage iterative methods for the solution of linear systems of algebraic equations are studied. Convergence is shown for monotone matrices and for -matrices. Two different asynchronous versions of these methods are considered and their convergence investigated. Received September 7, 1993 / Revised version received April 21, 1994     

Highly efficient single-pass source of pulsed single-mode twin beams of light

We report the realization of a bright ultrafast type II parametric down-conversion source of twin beams free of any spatiotemporal correlations in a periodically poled KTiOPO4 (PP-KTP) waveguide. From a robust, single-pass setup it emits pulsed two-mode squeezed vacuum states: photon-number entangled pairs of single-mode pulses or, in terms of continuous variables quantum optics, pulsed Einstein-Podolsky-Rosen states in the telecom wavelength regime. We verify the single-mode character of our source by measuring Glauber correlation functions g(2) and demonstrate with a pump energy as low as 75 pJ per pump pulse a mean photon number of 2.5.     

Quantum-confined electronic states in atomically well-defined graphene nanostructures

Despite the enormous interest in the properties of graphene and the potential of graphene nanostructures in electronic applications, the study of quantum-confined states in atomically well-defined graphene nanostructures remains an experimental challenge. Here, we study graphene quantum dots (GQDs) with well-defined edges in the zigzag direction, grown by chemical vapor deposition on an Ir(111) substrate by low-temperature scanning tunneling microscopy and spectroscopy. We measure the atomic structure and local density of states of individual GQDs as a function of their size and shape in the range from a couple of nanometers up to ca. 20 nm. The results can be quantitatively modeled by a relativistic wave equation and atomistic tight-binding calculations. The observed states are analogous to the solutions of the textbook "particle-in-a-box" problem applied to relativistic massless fermions.     

Widely tunable monolithic narrowband grating filter for near-infrared radiation

We propose a monolithic narrowband guided-mode grating filter in fused silica that is widely tunable in the near-IR wavelength region. Based on a recently demonstrated approach for a monolithic reflector comprising an encapsulated grating, we theoretically investigate such a device by means of rigorous modeling aimed at a narrow linewidth. It is demonstrated that upon a spatial variation of the filter's grating period its resonance wavelength can be tuned in a remarkably wide range of near-IR radiation with 800 nm<λ(res)< 1600 nm by translating the laser beam relative to the grating area. The filter performance in terms of linewidth and contrast is essentially preserved over the entire tuning interval.     

The Haar System as a Schauder Basis in Spaces of Hardy–Sobolev Type

We show that, for suitable enumerations, the Haar system is a Schauder basis in the classical Sobolev spaces in \({\mathbb R}^d\) with integrability \(1<p<\infty \) and smoothness \(1/p-1<s<1/p\). This complements earlier work by the last two authors on the unconditionality of the Haar system and implies that it is a conditional Schauder basis for a nonempty open subset of the (1 / p, s)-diagram. The results extend to (quasi-)Banach spaces of Hardy–Sobolev and Triebel–Lizorkin type in the range of parameters \(\frac{d}{d+1}<p<\infty \) and \(\max \{d(1/p-1),1/p-1\}<s<\min \{1,1/p\}\), which is optimal except perhaps at the end-points.     

Density functional calculation of the electronic circular dichroism spectra of the transition metal complexes [M(phen)3]2+ (M = Fe, Ru, Os)

The circular dichroism spectra of the tris-bidentate metal complexes Lambda-[M(phen)3]2+, with M = Fe, Ru, Os and phen = 1,10-tris-phenanthroline, are investigated computationally, employing time-dependent density functional theory. Good agreement with experimental spectra is obtained for Ru and Os. The Lambda-[Os(phen)3]2+ spectrum is analyzed in detail. It is shown how relativistic effects red shift CD bands where the Os 5d-orbital participates to a large extent in the excitations. Further, the participation of the metal in the ligand pi --> pi exciton CD is determined to be of the order of 10%. Though solvent effects can have a noticeable effect on individual transitions and rotatory strengths, they are demonstrated to have only a very small overall effect on the resulting simulated CD spectra. For Lambda-[Fe(phen)3]2+, the results are shown to be rather sensitive to the choice of the applied hybrid and nonhybrid density functionals, and the optimized geometries based thereupon. In particular, the sign pattern of the lower-energy part (up to 33 x 10(3) cm(-1)) of the Lambda-[Fe(phen)3]2+ CD spectrum is difficult to reproduce. Some combinations of functionals and geometries yield good agreement with experiment, but no "best" approach can be devised based on the available results. Possible sources of errors in the spectrum of Lambda-[Fe(phen)3]2+ due to deficiencies in the functionals and the exchange-correlation kernels are investigated.     

Comparison of hydrophilic-interaction, reversed-phase and porous graphitic carbon chromatography for glycan analysis

Hydrophilic-interaction liquid chromatography (HILIC), reversed-phase chromatography (RPC) and porous graphitic carbon (PGC) chromatography are typically applied for liquid chromatographic separations of protein N-glycans. Hence the performances of these chromatography modes for the separation of fluorescently labeled standard glycan samples (monoclonal antibody, fetuin, ribonuclease-B) covering high-mannose and a broad range of complex type glycans were investigated. In RPC the retention of sialylated glycans was enhanced by adding an ion-pairing agent to the mobile phase, resulting in improved peak shapes for sialylated glycans compared to methods recently reported in literature. For ion pairing RPC (IP-RPC) and HILIC ultra-high performance stationary phases were utilized to maximize the peak capacity and thus the resolution. But due to the shallow gradient in RPC the peak capacity was lower than on PGC. Retention times in HILIC and IP-RPC could be correlated to the monosaccharide compositions of the glycans by multiple linear regression, whereas no adequate model was obtained for PGC chromatography, indicating the significance of the three-dimensional structure of the analytes for retention in this method. Generally low correlations were observed between the chromatography methods, indicating their orthogonality. The high selectivities, as well as the commercial availability of ultra-high performance stationary phases render HILIC the chromatography method of choice for the analysis of glycans. Even though for complete characterization of complex glycan samples a combination of chromatography methods may be necessary.