Play, creativity, and adaptive functioning: implications for play interventions

This study focuses on the potential role for nitric oxide on the actions of the parasympathetic innervation to the heart. Earlier, we showed that the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) reduced the bradycardia induced by stimulation of vagal efferent motor fibres and that these effects are reversible through administration of the NOS substrate L-arginine. In the present study, we show that D-arginine does not reverse the effects of the inhibitors and confirm that they are reversed by L-arginine. Another NOS inhibitor, NG-nitro-L-arginine (L-NOARG), produced similar effects which were not reversed by L-arginine. In an examination of the effect of increasing NO availability with the NO donor sodium nitroprusside the vagally induced bradycardia was enhanced at all frequencies tested. In a separate series, the effects of NOS inhibitors and NO donors on the dromotropic actions of the vagus were examined. The NOS inhibitor L-NAME, reduced the increase in atrio-ventricular conduction delay normally induced by efferent vagal stimulation at all frequencies tested both in the 'paced' and 'unpaced' heart. Further, sodium nitroprusside enhanced this delay. Overall the study indicates that NO has an important facilitatory role on both the chronotropic and dromotropic actions of the vagus nerve on the heart and that NO may be a rate-limiting factor in the cardiac responses to vagal stimulation.     

Gulliver's further travels: the necessity and difficulty of a hierarchical theory of selection

For principled and substantially philosophical reasons, based largely on his reform of natural history by inverting the Paleyan notion of overarching and purposeful beneficence in the construction of organisms, Darwin built his theory of selection at the single causal level of individual bodies engaged in unconscious (and metaphorical) struggle for their own reproductive success. But the central logic of the theory allows selection to work effectively on entities at several levels of a genealogical hierarchy, provided that they embody a set of requisite features for defining evolutionary individuality. Genes, cell lineages, demes, species, and clades-as well as Darwin's favoured organisms-embody these requisite features in enough cases to form important levels of selection in the history of life. R. A. Fisher explicitly recognized the unassailable logic of species selection, but denied that thsi real process could be important in evolution because, compared with the production of new organisms within a species, the origin of new species is so rare, and the number of species within most clades so low. I review this and other classical arguments against higher-level selection, and conclude (in the first part of this paper) that they are invalid in practice for interdemic selection, and false in principle for species selection. Punctuated equilibrium defines the individuality of species and refutes Fisher's classical argument based on cycle time. In the second part of the paper, I argue that we have failed to appreciate the range and power of selection at levels above and below the organismic because we falsely extrapolate the defining properties of organisms to these other levels (which are characterized by quite different distinctive features), and then regard the other levels as impotent because their effective individuals differ so much from organisms. We would better appreciate the power and generality of hierarchical models of selection if we grasped two key principles: first, that levels can interact in all modes (positively, negatively, and orthogonally), and not only in the negative style (with a higher level suppressing an opposing force of selection from the lower level) that, for heuristic and operational reasons, has received almost exclusive attention in the existing literature; and second, that each hierarchical level differs from all others in substantial and interesting ways, both in the style and frequency of patterns in change and causal modes.     

Brownian motion on a square Lennard-Jones lattice: Trapping, hopping, and diffusion

Previously we showed that cGMP hydrolysis in rat whole retinal homogenates exhibited a dose-dependent inhibition following developmental lead exposure and a concentration-dependent inhibition with direct Pb2+ exposure. Additionally, developmental lead exposure resulted in a dose-dependent increase in retinal cGMP and rod Ca2+ levels. To determine whether Pb2+ or Ca2+ directly inhibited the rod-specific cGMP phosphodiesterase (PDE) and to examine the kinetic mechanism of this inhibition, purified bovine rod cGMP PDE was assayed in the presence of varying concentrations of cGMP, and Mg2+, Pb2+, and/or Ca2+. Increasing concentrations of the substrate, cGMP, resulted in a shift of the Pb2+ and Ca2+ concentration-response curves to the left, indicating a decrease in the half-maximal inhibitory concentrations of Pb2+ from nanomolar to picomolar levels. Increasing concentrations of the cofactor, Mg2+, resulted in a shift of the Pb2+ and Ca2+ concentration-response curves to the right, indicating a decrease in the inhibition of PDE activity by Pb2+ or Ca2+. A plot of 1/velocity vs 1/Mg2+ as a function of Pb2+ revealed that picomolar concentrations of Pb2+ competitively inhibited PDE relative to millimolar concentrations of Mg2+. Consistent with this finding, Mg2+ reversed the Pb(2+)-induced inhibition of PDE. Our recent kinetic analysis showed that Mg2+ and cGMP bind at interacting sites on the PDE in a random order. The present results reveal that Pb2+ may bind at the same site but with 4-6 log units higher affinity than Mg2+, thus preventing the hydrolysis of cGMP. These findings provide a novel mechanism for understanding the Pb(2+)-induced inhibition of cGMP PDE. These results may have implications for other enzymes using Mg2+ as a cofactor and suggest that Mg2+ may be useful in these situations for reversing the inhibition by Pb2+.     

Thermal fatigue of Ti-24Ai-11NB/SCS-6

The effect of thermally cycling in air with no applied load was studied using the Ti-24A1-11Nb (atomic percent)/SCS-6 composite system. Mechanisms of damage determination were observable cracking and residual tensile properties. Either the number of cycles or the temperature range was varied from specimen to specimen. Effects of number of cycles were investigated using a temperature range of 150 °C to 815 °C. Comparisons of temperature range effects were made at a constant cycle count of 500. Matrix cracking was observed at a †T of 450 °C and greater when oxidation was significant. Transverse cracking was not observed in specimens that were cycled to maximum temperatures where oxidation was insignificant, even for †T's as large as 500 °C. A decrease in tensile properties coincided with the observed transverse matrix cracking. This paper is based on a presentation made in the symposium “Interfaces and Surfaces of Titanium Materials” presented at the 1988 TMS/AIME fall meeting in Chicago, IL, September 25–29, 1988, under the auspices of the TMS Titanium Committee.     

Development of strategies for reducing air pollutant emissions in the European community

In view of increasing economic and environmental problems, energy supply strategies as well as air pollutant emission reduction strategies are required. These strategies should be designed in accordance with the specific development of a country or region. In the past they were mainly considered with respect to the finiteness of natural resources and the scarcity of economic resources. In recent years the ‘joint-production’ of air pollutant emissions in the energy sector has been increasingly recognized as an additional argument. As a consequence, concepts on future energy pathways, which should be efficient with respect to both economic development and environmental protection, have to be devised. For this purpose energy-environmental models such as EFOM-ENV can be used as analytic tools. The paper discusses optimal future energy supply structures that result from different strategies for air-pollution control in the countries of the European Community. The results have been obtained by applying the energy flow optimization model (EFOM), which has been extended by additional environmental modules to EFOM-ENV. The issues of the paper are based on research activities that the authors are performing for the Commission of the European Communities (CEC), Brussels, and the European Research Center for Air Pollution Control Measures (PEF), Karlsruhe, in close co-operation with research institutes in member countries of the European Community.