Sites of alcohol and volatile anaesthetic action on GABA(A) and glycine receptors

Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as gamma-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABA(A) and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA rho1 receptor is reduced. We have used this difference in pharmacology to investigate the molecular basis for modulation of these receptors by anaesthetics and alcohols. By using chimaeric receptor constructs, we have identified a region of 45 amino-acid residues that is both necessary and sufficient for the enhancement of receptor function. Within this region, two specific amino-acid residues in transmembrane domains 2 and 3 are critical for allosteric modulation of both GABA(A) and glycine receptors by alcohols and two volatile anaesthetics. These observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetics.     

Low-pressure pyrolysis studies of a new phosphorus precursor: Tertiarybutylbis(dimethylamino)phosphine

The low pressure decomposition of tertiarybutylbis(dimethylamino) phosphine, (t-Bu)P(NMe₂)₂, (TBBDMAP), has been studied on quartz and deposited GaP and InP surfaces. This new phosphorus precursor has been found to pyrolyze on quartz surfaces at much lower temperatures than the related compounds tertiarybutylphosphine, (t-Bu)PH₂, (TBP) and tris(dimethylamino)phosphorus, P(NMe₂)₃, (TDMAP). In contrast to the results obtained for TDMAP, GaP and InP surfaces decrease the decomposition temperature of TBBDMAP only slightly. The TBBDMAP reaction products were dimethylamine, methylmethyleneimine, and isobutylene, consistent with previous pyrolysis studies of TBP and TDMAP.     

Approximation eines Blockes durch einen äquivalenten Zylinder bei der Temperaturfeldberechnung

Überführung des zweidimensionalen Wärmeleitproblems eines Blockes mit quadratischem Querschnitt in ein eindimensionales Wärmeleitproblem für einen Zylinder mit äquivalentem Querschnitt. Temperaturfeldberechnung mit zweidimensionalem Blockmodell mittels digitaler Simulation als Voraussetzung der Bestimmung der Parameter des äquivalenten Zylindermodells.     

The European Radiobiology Archives (ERA), present state and future developments

The European Radiobiology Archives (ERA) aims to collect most of the information still available in Europe on long-term animal experiments--including some selected human studies suitable for comparison with animal data--and to make them available to the scientific community for further analysis. ERA cooperates with the US (National Radiobiology Archives, NRA) and Japan (Japanese Radiobiology Archives, JRA) in the International Radiobiology Archives (IRA).     

Development of a flow controller for long-term sampling of gases and vapors using evacuated canisters

Anthropogenic activities contribute to the release of a wide variety of volatile organic compounds (VOC) into microenvironments. Developing and implementing new air sampling technologies that allow for the characterization of exposures to VOC can be useful for evaluating environmental and health concerns arising from such occurrences. A novel air sampler based on the use of a capillary flow controller connected to evacuated canisters (300 mL, 1 and 6 L) was designed and tested. The capillary tube, used to control the flow of air, is a variation on a sharp-edge orifice flow controller. It essentially controls the velocity of the fluid (air) as a function of the properties of the fluid, tube diameter and length. A model to predict flow rate in this dynamic system was developed. The mathematical model presented here was developed using the Hagen-Poiseuille equation and the ideal gas law to predict flow into the canisters used to sample for long periods of time. The Hagen-Poiseuille equation shows the relationship between flow rate, pressure gradient, capillary resistance, fluid viscosity, capillary length and diameter. The flow rates evaluated were extremely low, ranging from 0.05 to 1 mL min(-1). The model was compared with experimental results and was shown to overestimate the flow rate. Empirical equations were developed to more accurately predict flow for the 300 mL, 1 and 6 L canisters used for sampling periods ranging from several hours to one month. The theoretical and observed flow rates for different capillary geometries were evaluated. Each capillary flow controller geometry that was tested was found to generate very reproducible results, RSD < 2%. Also, the empirical formulas developed to predict flow rate given a specified diameter and capillary length were found to predict flow rate within 6% of the experimental data. The samplers were exposed to a variety of airborne vapors that allowed for comparison of the effectiveness of capillary flow controllers to sorbent samplers and to an online gas chromatograph. The capillary flow controller was found to exceed the performance of the sorbent samplers in this comparison.     

Finite elements for fluid–structure interaction in ALE and fully Eulerian coordinates

In this work we describe and compare two monolithic models for fluid–structure interaction problems: First, the well-established ALE model using natural Lagrangian coordinates for the structural model and using an artificial coordinate system for the flow problem. Then, a novel approach, the fully Eulerian coordinates, where both subproblems, structure and fluid are given in Eulerian coordinates. The approaches have in common that a closed variational formulation exists. This allows the use of implicit solution schemes, goal oriented error estimation and gradient based optimization algorithms.Aim of this work is the introduction and verification of the novel fully Eulerian model for stationary fluid–structure interaction problems.     

CVT-313, a specific and potent inhibitor of CDK2 that prevents neointimal proliferation

The activity of cyclin-dependent kinase 2 (CDK2) is essential for progression of cells from G1 to the S phase of the mammalian cell cycle. CVT-313 is a potent CDK2 inhibitor, which was identified from a purine analog library with an IC50 of 0.5 microM in vitro. Inhibition was competitive with respect to ATP (Ki = 95 nM), and selective CVT-313 had no effect on other, nonrelated ATP-dependent serine/threonine kinases. When added to CDK1 or CDK4, a 8.5- and 430-fold higher concentration of CVT-313 was required for half-maximal inhibition of the enzyme activity. In cells exposed to CVT-313, hyperphosphorylation of the retinoblastoma gene product was inhibited, and progression through the cell cycle was arrested at the G1/S boundary. The growth of mouse, rat, and human cells in culture was also inhibited by CVT-313 with the IC50 for growth arrest ranging from 1.25 to 20 microM. To evaluate the effects of CVT-313 in vivo, we tested this agent in a rat carotid artery model of restenosis. A brief intraluminal exposure of CVT-313 to a denuded rat carotid artery resulted in more than 80% inhibition of neointima formation. These observations suggest that CVT-313 is a promising candidate for evaluation in other disease models related to aberrant cell proliferation.     

Dissolved organic carbon enhances the mass transfer of hydrophobic organic compounds from nonaqueous phase liquids (NAPLs) into the aqueous phase

The hypothesis that dissolved organic carbon (DOC) enhances the mass transfer of hydrophobic organic compounds from nonaqueous phase liquids (NAPLs) into the aqueous phase above that attributable to dissolved molecular diffusion alone was tested. In controlled experiments, mass transfer rates of five NAPL-phase PAHs (log K(OW) 4.15-5.39) into the aqueous phase containing different concentrations of DOC were measured. Mass transfer rates were increased by up to a factor of 4 in the presence of DOC, with the greatest enhancement being observed for more hydrophobic compounds and highest DOC concentrations. These increases could not be explained by dissolved molecular diffusion alone, and point to a parallel DOC-mediated diffusive pathway. The nature of the DOC-mediated diffusion pathway as a function of the DOC concentration and PAH sorption behavior to the DOC was investigated using diffusion-based models. The DOC-enhanced mass transfer of NAPL-phase hydrophobic compounds into the aqueous phase has important implications for their bioremediation as well as bioconcentration and toxicity.     

Automated reasoning about elementary point-set topology

In this paper we present first-order formulas for basic point-set topology, in an attempt to extend the mathematical range available for exploration with automated theorem-proving programs. We present topology definitions and sample lemmas both in first-order logic and in clausal form. We then illustrate some of the difficulties of these sample lemmas through a proof of a basic lemma in five parts.This work was supported by the Applied Mathematical Sciences subprogram of the Office of Energy Research, U.S. Department of Energy, under contract W-31-109-Eng-38, and by the Division of Educational Programs, Argonne National Laboratory.     

Curli, fibrous surface proteins of Escherichia coli, interact with major histocompatibility complex class I molecules

Curli are thin, coiled fibers expressed on the surface of Escherichia coli that bind several matrix and plasma proteins such as fibronectin, laminin, plasminogen, tissue plasminogen activator, and H-kininogen. In this work, we examined the interactions between curli-expressing E. coli and human major histocompatibility complex class I (MHC-I) and class II (MHC-II) molecules. Curliated E. coli was found to interact with an MHC-I-expressing lymphoma cell line as shown by scanning electron microscopy, whereas the binding to a mutant variant of this cell line expressing small amounts of MHC-I molecules was significantly lower. Moreover, curli-expressing E. coli bound purified radiolabeled MHC-I but not MHC-II molecules, whereas an isogenic curli-deficient mutant strain showed no affinity for either MHC-I or MHC-II. Purified insoluble curli could also bind 125I-labeled MHC-I molecules, and in Western blot experiments the 15-kDa curlin subunit protein bound intact MHC-I molecules as well as beta2-microglobulin, the light chain of MHC-I molecules. A direct interaction between monomeric MHC-I molecules and a bacterial surface protein has previously not been reported. The binding of curli to MHC-I molecules, which are present on virtually all cells in higher vertebrates, will provide curliated E. coli with ample opportunities to interact with a great variety of hosts and host cells. This should facilitate the adaptation of E. coli to different ecological niches, and in human infections the interaction between curli and MHC-I molecules could contribute to adherence and colonization.