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.     

Carbon fibre composites based on polyimide/silica ceramers: aspects of structure-properties relationship

Polyimide/silica ceramers, based on the products of the hydrolysis of tetraethoxysilane (TEOS) and a commercial poly(amic acid) solution, were used to fabricate unidirectional carbon fibre composites, which were subsequently evaluated with respect to thermal and mechanical properties. There is evidence to suggest that the silica component of these ceramers is present as dispersed discrete particles at low silica concentration (i.e. 7 wt%) and as fine interconnected domains trapped within the polyimide matrix at higher silica content (i.e. 14 wt%). The dimensions of the silica domains were in the region of 7–20 nm. Carbon fibre composites produced from ceramer solutions (CF/ceramers) were found to exhibit lower thermal expansion and a greater retention of flexural and interlaminar shear properties at elevated temperature than the corresponding polyimide-matrix composites (CF/polyimide). The properties of CF/ceramers were generally better for systems containing the higher amount of silica and were improved further by lowering the pH value of the precursor ceramer solution. This is believed to have resulted from the enhanced fluidity of the ceramer gel within the pre-impregnated fibres, giving rise to a higher packing density of the fibres and a more homogeneous distribution of fibres. CF/ceramers were also found to exhibit a better thermal oxidative stability at 350°C than the corresponding CF/polyimide, although a substantial amount of porosity developed in the case of ceramers with the higher silica content.     

Silane functionalization of perfluoroether oligomers for reaction management and morphology control of two‐phase epoxy networks

Mixtures of an epoxy resin, hardener, and acid functionalized perfluoroether oligomers will readily undergo phase separation during curing. However, the conditions to bring about the growth of nuclei into microscopic particles have hitherto been found only for systems cured with anhydrides. In the present study perfluoroether oligomers were functionalized by established procedures to introduce both carboxylic acid groups and alkoxysilane groups in sites within the chain extended segments. The presence of alkoxysilane groups together with the prereaction step with an excess epoxy resin, prior to the addition of the aromatic amine hardener, induced phase separation by a nucleation‐and‐growth mechanism. The dual functionality in the perfluoroether oligomer was even more beneficial when the alkoxysilane groups were hydrolyzed prior to the addition of the amine hardener. Under such circumstances the precipitation of the perfluoroether oligomer occurred quantitatively, as indicated by the complete absence of any plasticization effects in the epoxy matrix. From electron microscopy examinations, thermal analysis, and measurements of mechanical properties it was possible to deduce a plausible mechanism for the formation of the typical core‐shell aggregates within the precipitated particles for these systems, which could also be applied to other systems, such as those using carboxylic‐acid‐terminated butadiene acrylonitrile oligomers. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 98: 1036–1049, 2005     

Effects of perfluoroether concentration and curing protocol on morphology and mechanical properties of toughened TGDDM/MNA resin systems

Previous published work has shown that hydroxyl terminated perfluoroether oligomers can be suitably modified and functionalised to make them miscible with epoxy resins in the uncured state. The reaction conditions can adjusted to induce phase separation either through spinodal decomposition to produce an IPN type morphology, or by nucleation and growth if a dispersed-particle microstructure is required.In the present work we examine the relative toughening enhancement efficiency of the two possible heterophase morphologies. Both systems show a sigmoidal increase in fracture toughness, with increasing concentration of the perfluoroether modifier. However, this takes place at much lower modifier concentrations for the systems with a particulate morphology (about 3.5% w/w) than for IPN systems (about 7.5% w/w). The maximum fracture toughness achievable for the two systems, on the other hand, is very similar and coincides with the concentration at which co-continuous phases are formed.These differences in morphology, however, are not reflected in the variation of modulus and compressive yield strength with increasing concentration of perfluoroether modifier, in so far as both systems exhibit a gradual and small reduction in property with increasing concentration. Furthermore, the dynamic mechanical spectra of the two systems are very different, but the changes resulting from increasing the concentration of toughening agent are relatively small in either case.Nanoindentation tests indicate that it is the local plasticity, brought about by the presence of the softer perfluoroether phase, which is responsible for the enhancement of fracture toughness. This is corroborated by AFM examinations, which reveal local plastic deformations in the regions surrounding the softer particles.     

On the sensitivity of reactive tabu search to its meta-parameters

In this paper, we assess the sensitivity of reactive tabu search to its meta-parameters. Based on a thorough experimental analysis of reactive tabu search applications to the quadratic assignment and the maximum clique problem, we show that its performance is relatively insensitive to its meta-parameters. This is particularly evident when compared to the sensitivity of tabu search to its parameters: tabu search is rather penalized if used with sub-optimal parameter settings. Reactive tabu search does not strongly pay its high parameter robustness in terms of performance, although it does not improve the peak performance of tabu search.     

An elitist strategy genetic algorithm using simulated annealing algorithm as local search for facility layout design

A well-planned arrangement of manufacturing departments on a two-dimensional planar region considerably increases the efficiency of its production systems, which is termed facility layout problem (FLP). Conventional layout design approach often designs intercell layout (determining exact location of each department on shop floor area) and flow path layout design of material handling system (MHS) step by step in a sequential manner. This results in suboptimal solutions for FLP. In this paper, an integrated approach is adopted to design the intercell layout and the flow path layout of MHS simultaneously. The quality of the final layout is evaluated by minimizing total material handling cost. Sequence pair (SP) representation is used for layout encoding. The translation from SP to layout is efficiently made by longest common subsequence (LCS) methodology. An elitist strategy genetic algorithm using simulated annealing (E-GASAA) as a local search mechanism is developed and tested with four test problem instances available in the literature. Elitist strategy is incorporated to enhance convergence characteristic of the proposed algorithm. It is found that the proposed E-GASAA is able to produce best solutions consistently for the test problem instance of different sizes within acceptable computational effort. In addition to that, we tried to reduce the computational load with the help of adopted LCS computation methodology and achieved a good improvement.     

Controlling the Er content of porous silicon using the doping current intensity

The results of an investigation on the Er doping of porous silicon are presented. Electrochemical impedance spectroscopy, optical reflectivity, and spatially resolved energy dispersive spectroscopy (EDS) coupled to scanning electron microscopy measurements were used to investigate on the transient during the first stages of constant current Er doping. Depending on the applied current intensity, the voltage transient displays two very different behaviors, signature of two different chemical processes. The measurements show that, for equal transferred charge and identical porous silicon (PSi) layers, the applied current intensity also influences the final Er content. An interpretative model is proposed in order to describe the two distinct chemical processes. The results can be useful for a better control over the doping process.

PACS

81.05.Rm; 82.45.Rr     

Histone H1 reduces the frequency of initiation in Xenopus egg extract by limiting the assembly of prereplication complexes on sperm chromatin

Somatic histone H1 reduces both the rate and extent of DNA replication in Xenopus egg extract. We show here that H1 inhibits replication directly by reducing the number of replication forks, but not the rate of fork progression, in Xenopus sperm nuclei. Density substitution experiments demonstrate that those forks that are active in H1 nuclei elongate to form large tracts of fully replicated DNA, indicating that inhibition is due to a reduction in the frequency of initiation and not the rate or extent of elongation. The observation that H1 dramatically reduces the number of replication foci in sperm nuclei supports this view. The establishment of replication competent DNA in egg extract requires the assembly of prereplication complexes (pre-RCs) on sperm chromatin. H1 reduces binding of the pre-RC proteins, XOrc2, XCdc6, and XMcm3, to chromatin. Replication competence can be restored in these nuclei, however, only under conditions that promote the loss of H1 from chromatin and licensing of the DNA. Thus, H1 inhibits replication in egg extract by preventing the assembly of pre-RCs on sperm chromatin, thereby reducing the frequency of initiation. These data raise the interesting possibility that H1 plays a role in regulating replication origin use during Xenopus development.     

Molybdate doping of networks in epoxy–silica hybrids: Domain structuring and corrosion inhibition

Epoxy–silica hybrids were prepared from a silane-functionalized resin mixture of two diglycidyl ether bis-phenol A oligomers with different molecular weights, using molybdate anions as dopants for the siloxane domains.