Analogues of capsaicin with agonist activity as novel analgesic agents; structure-activity studies. 3. The hydrophobic side-chain "C-region"

Structural variants of the hydrophobic side chain ("C region") of the capsaicin molecule have been incorporated into a series of vanillylamides and vanillylthioureas. These compounds have been tested in an in vitro assay for agonism (45Ca2+ influx into dorsal root ganglia neurones), previously shown to be predictive of analgesic activity. The results of this study have established the requirement for a hydrophobic substituent of limited size (molar refractivity, MR, < 55) in order to obtain high potency. Combination of the information gained here about the "C-region" of the capsaicin molecule with the studies described in the preceding two papers provides a rational basis for the design of compounds of increased potency.     

Differential effects of elevated potassium ion concentration and of theophylline on growth hormone release by rat adenohypophyses in vitro

The effects of 27 mM K+ and of 6.7 mM theophylline on the release of growth hormone (GH) by rat hemipituitaries in vitro were investigated using bioassay (rat tibia test) and radioimmunoassay (RIA). Both agents markedly increased the release of immunoreactive GH. High K+ also promoted the release of bioactive GH but to a much lesser degree than RIA-GH. Theophylline did not consistently affect the release of bioassay-detectable GH. The results suggest that these agents promote massive release of a form of immunoreactive GH (possibly "immature") that has little or no activity in the bioassay. Theophylline is relatively more effective in this regard than is elevated K+.     

Tests During Three Stages of Construction of a Road Bridge with a Flexible Load-Carrying Structure Made of Super Cor Type Steel Corrugated Plates Interacting with Soil

The way in which a new road bridge made of steel corrugated plates Super Cor type was tested during the three stages of its construction is described and the test results are presented. Backfill in construction Stage I and two ballasting vehicles in Stages II and III constituted the loads. The box bridge spans the Bystrzyca Dusznicka River in Polanica Zdroj, Poland. The span’s effective length is 12.27?m and its vertical inside diameter is 3.85?m. The steel span is founded on two reinforced concrete strip foundations. The average values of the displacements and strains (normal stresses) measured in selected points and on selected elements of the steel shell structure were much smaller than the ones computed for the same load. The conclusions drawn from this research can be helpful in determining the interaction between the steel shell and the backfill. Since this type of steel–soil structure is increasingly used in Poland and in the world, the conclusions can be generalized to a whole class of similar bridge designs.     

Land use regression model for ultrafine particles in Amsterdam

There are currently no epidemiological studies on health effects of long-term exposure to ultrafine particles (UFP), largely because data on spatial exposure contrasts for UFP is lacking. The objective of this study was to develop a land use regression (LUR) model for UFP in the city of Amsterdam. Total particle number concentrations (PNC), PM10, PM2.5, and its soot content were measured directly outside 50 homes spread over the city of Amsterdam. Each home was measured during one week. Continuous measurements at a central urban background site were used to adjust the average concentration for temporal variation. Predictor variables (traffic, address density, land use) were obtained using geographic information systems. A model including the product of traffic intensity and the inverse distance to the nearest road squared, address density, and location near the port explained 67% of the variability in measured PNC. LUR models for PM2.5, soot, and coarse particles (PM10, PM2.5) explained 57%, 76%, and 37% of the variability in measured concentrations. Predictions from the PNC model correlated highly with predictions from LUR models for PM2.5, soot, and coarse particles. A LUR model for PNC has been developed, with similar validity as previous models for more commonly measured pollutants.     

The amount of information and the volume of ‘information tare’

A distinction is suggested between the notions ‘information tare’, the role of which is played by the signals or letters forming the message, and ‘information’, which may be contained in such messages. It is shown that Shannon's definition of the amount of information is, in fact, the definition of the volume of information tare, whereas the amount of information itself may be measured as the volume of information tare of the maximally compact message used for its recording. This allows one to express both the volume of information tare, H, and the amount of information, B, in the same units of measurement–bits–and for any message B≤H. Some consequences of these views are analysed.     

Minimizing photodecomposition of flavin adenine dinucleotide fluorescence by the use of pulsed LEDs

Dynamic alterations in flavin adenine dinucleotide (FAD) fluorescence permit insight into energy metabolism‐dependent changes of intramitochondrial redox potential. Monitoring FAD fluorescence in living tissue is impeded by photobleaching, restricting the length of microfluorimetric recordings. In addition, photodecomposition of these essential electron carriers negatively interferes with energy metabolism and viability of the biological specimen. Taking advantage of pulsed LED illumination, here we determined the optimal excitation settings giving the largest fluorescence yield with the lowest photobleaching and interference with metabolism in hippocampal brain slices. The effects of FAD bleaching on energy metabolism and viability were studied by monitoring tissue pO₂, field potentials and changes in extracellular potassium concentration ([K⁺]_o). Photobleaching with continuous illumination consisted of an initial exponential decrease followed by a nearly linear decay. The exponential decay was significantly decelerated with pulsed illumination. Pulse length of 5 ms was sufficient to reach a fluorescence output comparable to continuous illumination, whereas further increasing duration increased photobleaching. Similarly, photobleaching increased with shortening of the interpulse interval. Photobleaching was partially reversible indicating the existence of a transient nonfluorescent flavin derivative. Pulsed illumination decreased FAD photodecomposition, improved slice viability and reproducibility of stimulus‐induced FAD, field potential, [K⁺]_o and pO₂ changes as compared to continuous illumination.     

Vapor- and liquid-phase adsorption of alcohol and water in silicalite-1 synthesized in fluoride media

In this work, batch-adsorption experiments and molecular simulations are employed to probe the adsorption of binary mixtures containing ethanol or a linear alkane-1,n-diol solvated in water or ethanol onto silicalite-1. Since the batch-adsorption experiments require an additional relationship to determine the amount of solute (and solvent) adsorbed, as only the bulk liquid reservoir can be probed directly, molecular simulations are used to provide a relationship between solute and solvent adsorption for input to the experimental bulk measurements. The combination of bulk experimental measurements and simulated solute–solvent relationship yields solvent and solute loadings that are self-consistent with simulation alone, and allow for an assessment of the various assumptions made in the literature. At low solution concentrations, the solute loading calculated is independent of the assumption made. At high concentrations, a negligent choice of assumption can lead to systematic overestimation or underestimation of calculated solute loading.