Synthesis and Evaluation of Voltage-Gated Sodium Channel Blocking Pyrroline Derivatives Endowed with Both Antiarrhythmic and Antioxidant Activities

Under the hypothesis that cardioprotective agents might benefit from synergism between antiarrhythmic activity and antioxidant properties, a small series of mexiletine analogues were coupled with the 2,2,5,5-tetramethylpyrroline moiety, known for its antioxidant effect, in order to obtain dual-acting drugs potentially useful in the protection of the heart against post-ischemic reperfusion injury. The pyrroline derivatives reported herein were found to be more potent as antiarrhythmic agents than mexiletine and displayed antioxidant activity. The most interesting tetramethylpyrroline congener, a tert-butyl-substituted analogue, was at least 100 times more active as an antiarrhythmic than mexiletine.     

Characterization of the Functional Cross-Talk between Surface GABAA and Dopamine D5 Receptors

The γ-aminobutyric acid type A receptor (GABA_AR) plays a major role in fast inhibitory synaptic transmission and is highly regulated by the neuromodulator dopamine. In this aspect, most of the attention has been focused on the classical intracellular signaling cascades following dopamine G-protein-coupled receptor activation. Interestingly, the GABA_AR and dopamine D5 receptor (D5R) have been shown to physically interact in the hippocampus, but whether a functional cross-talk occurs is still debated. In the present study, we use a combination of imaging and single nanoparticle tracking in live hippocampal neurons to provide evidence that GABA_ARs and D5Rs form dynamic surface clusters. Disrupting the GABA_AR–D5R interaction with a competing peptide leads to an increase in the diffusion coefficient and the explored area of both receptors, and a drop in immobile synaptic GABA_ARs. By means of patch-clamp recordings, we show that this fast lateral redistribution of surface GABA_ARs correlates with a robust depression in the evoked GABAergic currents. Strikingly, it also shifts in time the expression of long-term potentiation at glutamatergic synapses. Together, our data both set the plasma membrane as the primary stage of a functional interplay between GABA_AR and D5R, and uncover a non-canonical role in regulating synaptic transmission.     

Kinetics of chemical n-doping of polyacetylene

Polyacetylene (PA) films were doped with tetrahydrofuran and benzene solutions of organo potassium and lithium compounds. The kinetics for doping were determined from the variation of the dopant concentration with time, as a function of film thickness, dopant concentration and doping temperature. The experimental doping rates were compared to computed values deduced from a doping model taking into account the interfibrillar diffusion, separately measured with an inert hydrocarbon. This comparison allows a minimum value (10⁻¹⁵ cm²/s) to be determined for the intrafibrillar diffusion coefficient D_f of doped sites and cations. With such a value no homogeneous doping can be carried out at intermediate doping levels, for films thicker than about 50 microns, by a simple control of doping time or dopant concentration. This may, however, be achieved by a thermodynamic control using dopants of suitable redox potential.     

Microstructure and Mechanical Properties of Hot-Pressed Silicon Carbide-Aluminum Nitride Compositions

A flexural strength of up to 1 GPa was achieved in SiC-AIN materials and is attributed to a dense, equiaxial grain structure of the 2H(δ) SiC-AIN solid solution, with a relatively uniform grain size of ∼ 1 μm. The strength was found to decrease with increasing grain size. While the β→α phase transformation and the formation of various metastable polytypes make microstructural control difficult in SiC materials, excellent control is facilitated in SiC-AIN materials as a result of the stable 2H solid solution. Several mechanisms of grain refinement during the β→ 2H transition were observed, most notably the direct formation of several 2H grains from a single β grain. In addition, grain growth is limited by the diffusion-controlled nature of the transition. These mechanisms could be utilized to achieve even higher strength values, with potentially higher reliability of the materials in structural applications.     

Testing usability and trainability of indirect touch interaction: perspective for the next generation of air traffic control systems

This study aims to determine whether indirect touch device can be used to interact with graphical objects displayed on another screen in an air traffic control (ATC) context. The introduction of such a device likely requires an adaptation of the sensory-motor system. The operator has to simultaneously perform movements on the horizontal plane while assessing them on the vertical plane. Thirty-six right-handed participants performed movement training with either constant or variable practice and with or without visual feedback of the displacement of their actions. Participants then performed a test phase without visual feedback. Performance improved in both practice conditions, but accuracy was higher with visual feedback. During the test phase, movement time was longer for those who had practiced with feedback, suggesting an element of dependency. However, this ‘cost’ of feedback did not extend to movement accuracy. Finally, participants who had received variable training performed better in the test phase, but accuracy was still unsatisfactory. We conclude that continuous visual feedback on the stylus position is necessary if tablets are to be introduced in ATC.     

Efficient Binary Tomographic Reconstruction

Tomographic reconstruction of a binary image from few projections is considered. A novel heuristic algorithm is proposed, the central element of which is a nonlinear transformation ψ(p)=log(p/(1?p)) of the probability p that a pixel of the sought image be 1-valued. It consists of backprojections based on ψ(p) and iterative corrections. Application of this algorithm to a series of artificial test cases leads to exact binary reconstructions, (i.e., recovery of the binary image for each single pixel) from the knowledge of projection data over a few directions. Images up to 10⁶ pixels are reconstructed in a few seconds. A series of test cases is performed for comparison with previous methods, showing a better efficiency and reduced computation times.     

Characterization of Maximum Likelihood Solutions to Image Reconstruction in Photon Emission Tomography

For photon emission tomography, the maximum likelihood (ML) estimator for image reconstruction is generally solution to a nonlinear equation involving the vector of measured data. No explicit closed-form solution is known in general for such a nonlinear ML equation, and numerical resolution is usually implemented, with a very popular iterative method formed by the expectation-maximization algorithm. The numerical character of such resolutions usually makes it difficult to obtain a general characterization of the performance of the ML solution. We show that the nonlinear ML equation can be replaced by an equivalent system of two dual linear equations nonlinearly coupled. This formulation allows us to exhibit explicit (to some extent) forms for the solutions to the ML equation, in general conditions corresponding to the various possible configurations of the imaging system, and to characterize their performance with expressions for the mean-squared error, bias and Cramér-Rao bound. The approach especially applies to characterize the ML solutions obtained numerically, and offers a theoretical framework to contribute to better appreciation of the capabilities of ML reconstruction in photon emission tomography.     

Syndiotactic Polystyrene/Organoclay Nanocomposites: Synthesis via In Situ Coordination‐Insertion Polymerization and Preliminary Characterization

Summary: Syndiotactic polystyrene (sPS)/organophilic clay nanocomposites were obtained by in situ coordination‐insertion polymerization of styrene. Two cationic surfactants (alkylammonium and alkylphosphonium) were used for the intercalation of montmorillonite (MMT). For each organically modified clay, three protocols were performed using an MAO‐activated hemi‐metallocene catalyst, in order to compare the influence of experimental conditions on the composite microstructure and on its thermal stability. The microstructures of nanocomposites were investigated by wide angle X‐ray scattering and DSC. Partially exfoliated or intercalated materials were obtained in all cases and a decrease of crystallinity is observed. Thermal properties were also studied by DSC and thermogravimetric analysis. The presence of clay does not have a strong influence on the sPS thermal transitions but the thermal decomposition process of the material was slowed down in the presence of few organoclay percents, particularly in the degradation beginning. The influence of these two organically modified clays on the thermal stability of the material is discussed.

Gel and suspension formed from the combination of cloisite with toluene (left) and styrene (right), respectively.     

Cure kinetics of an epoxy/liquid aromatic diamine modified with poly(ether imide)

The cure kinetics and mechanisms of an epoxy oligomer based on diglycidyl ether of bisphenol A (DGEBA), polymerized with a liquid aromatic diamine based on diethyl toluene diamine (DETDA 80), and its blends with poly(ether imide) (PEI) at concentrations of 0–15 wt % were studied with differential scanning calorimetry under dynamic and isothermal conditions. The kinetic analyses were performed with a phenomenological approach. The reaction mechanism of the blends remained the same as that of the neat epoxy. However, the addition of PEI had a marked effect on the cure kinetics in the DGEBA/DETDA 80 system. The rate of reaction decreased with an increase in the thermoplastic content. Diffusion control was incorporated to describe the cure behavior of the blends in the latter stages. Greater diffusion control was observed as the PEI concentration increased and the cure temperature decreased. Polymer blends based on this epoxy/liquid aromatic diamine had not been previously studied from a kinetic viewpoint. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci 96: 660–672, 2005