We have investigated various nitric oxide (NO) synthase inhibitors for their affinity and selectivity toward the three human isoenzymes in radioligand binding experiments. Therefore, we developed the new radioligand [(3)H]2-amino-4-picoline to measure binding of these compounds to the three human NO synthase (NOS) isoenzymes. Aminopicoline is a potent and nonselective inhibitor of all three isoforms. [(3)H]2-amino-4-picoline bound saturably and with high affinity to human NOSs. Affinity constants (K(D) values) of 59, 111, and 136 nM were obtained for the inducible, neuronal, and endothelial NOS isoforms (iNOS, nNOS, eNOS). Binding of [(3)H]2-amino-4-picoline was competitive with the substrate arginine. From all the inhibitors tested, AMT (2-amino-5, 6-dihydro-6-methyl-4H-1,3-thiazine hydrochloride) showed the highest affinity and no selectivity. L-NIL [L-N(6)-(1-Iminoethyl)lysine hydrochloride] and aminoguanidine were moderately iNOS-selective while L-NA (N(G)-nitro-L-arginine) and L-NAME (N(G)-nitro-L-arginine methyl ester hydrochloride) showed selectivity toward the constitutive isoforms. High iNOS versus eNOS selectivity was found for 1400W, whereas several isothiourea derivatives and 1400W displayed moderate n- versus eNOS selectivity. To relate the affinity of these compounds to their inhibitory potency, we measured the inhibitory potency under almost identical conditions using a new microtiter plate assay. The inhibitory potency of selective and nonselective NOS inhibitors was almost exactly mirrored by their affinity toward the different isoenzymes. Highly significant correlations were obtained between the potency of enzyme inhibition and the inhibition of [(3)H]2-amino-4-picoline binding for all three isoenzymes. These data show that the potency and selectivity of NOS inhibitors are solely determined by their affinity toward the different isoforms. Furthermore, these data identify the new radioligand [(3)H]2-amino-4-picoline as a very useful radiolabel for the investigation of the substrate binding site of all three isoforms.
Photoelectrochemical water splitting promises both sustainable energy generation and energy storage in the form of hydrogen. However, the realization of this vision requires laboratory experiments to be engineered into a large-scale technology. Up to now only few concepts for scalable devices have been proposed or realized. Here we introduce and realize a concept which, by design, is scalable to large areas and is compatible with multiple thin-film photovoltaic technologies. The scalability is achieved by continuous repetition of a base unit created by laser processing. The concept allows for independent optimization of photovoltaic and electrochemical part. We demonstrate a fully integrated, wireless device with stable and bias-free operation for 40 h. Furthermore, the concept is scaled to a device area of 64 cm2 comprising 13 base units exhibiting a solar-to-hydrogen efficiency of 3.9%. The concept and its successful realization may be an important contribution towards the large-scale application of artificial photosynthesis.
We observe coherent long-distance propagation of an optical pulse in resonance with the free exciton at high light intensities in an optically thick semiconductor. The experiments show pulse reshaping, pulse breakup, and a high degree of transmission. Microscopic calculations using the semiconductor Maxwell-Bloch equations yield good agreement with the experimental data. [S0031-9007 (98)07576-0] PACS numbers: 78.20.Bh, 71.35.GgPropagation experiments with short light pulses are crucial for the simultaneous study of temporal and spatial coherence in matter. In semiconductors, as opposed to atomic systems which can be modeled by noninteracting two-level systems [1], spatial dispersion [2] and excitationinduced nonlinearities of the excitonic resonance [3][4][5] will result in remarkable modifications of the pulse propagation features. At low light intensities, temporal polariton beating of the transmitted pulse has been observed and shows excellent agreement with linear dispersion theory [6]. In nonlinear experiments, however, many-body effects (such as exciton-exciton collisions), unknown in atomic systems, will destroy the polariton beating after the pulse by interaction-induced dephasing [7-9]. Let us recall the situation in idealized two-level systems: Rabi oscillations (coherent electron density oscillations) lead to lossless soliton propagation of 2p pulses-so-called self-induced transparency (SIT)-and pulse breakup for input pulse areas larger than 3p [10]. Following this area theorem [11], SIT was pioneered in atomic vapor about 25 years ago [12]. In semiconductors, SIT has been demonstrated on bound excitons in CdS [13], which resemble ideal noninteracting two-level systems due to the restricted wave function overlap between different excitons. So far, SIT had not been found on free excitons and the chances for its discovery are low because theoretical investigations [14,15] came to the conclusion that interaction-induced dephasing between excitons with overlapping wave functions will reduce the polarization coherence necessary for the establishment of complete pulse transmission. On the other hand, the appearance of Rabi oscillations in semiconductors [14,[16][17][18], as well as propagation over long distances [19], has been predicted at light intensities larger than p. Thus at least partially coherent propagation should be feasible. In this Letter, we will show experimentally that coherent long-distance propagation and multiple-pulse breakup on a free exciton resonance in a semiconductor at high light intensities is possible. Because many observed features resemble SIT in atomic systems, we will call this newly observed phenomenon self-induced transmission in semiconductors.We used 50-80 fs pulses around 680 nm with pulse energies of about 100 nJ from an optical parametric amplifier [20] pumped by a regenerative Ti:sapphire amplifier (COHERENT REGA) at 200 kHz. Careful alignment using FROG [21] made sure that the pulses were chirp-free, which is essential for the experiment. The pulses were focused onto...
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