Computer simulations of signal transduction mechanism in {alpha}1B-adrenergic and m3-muscarinic receptors

Molecular dynamices simulations of the hamster _1Badrenergicand the rat m3-muscarinic seven-helix bundle receptor modelshave been carried out. The free, agonist-bound and antagonist-boundforms have been considered. Moreover, three mutant forms ofthe m3-muscarinic recep-tor (N507A, N507D and N507S) have alsobeen simulated; among these, the N507S mutant shows a constitutiveactivity. A comparative structural/dynamics analysis has beenperformed to elucidate (i) the perturbations induced by thefunctionally different ligands upon binding to their targetreceptor, (ii) the features of the three single-point mutantswith respect to the receptor wild type and (iii) the propertiesshared by the agonist-boundforms of the _1B-adrenergic receptorand the m3-muscarinic receptor and by the constitutively activemutant N507S. The consistency obtained between the structuralrearrangement of the transmembrane seven-helix bundle modelsconsidered, and the experimental pharmacological efficaciesof the ligands and of the mutants, constitute an important validationof the 3-D models obtained and allow the inference of the mechanismof ligand- or mutation-induced receptor activation at the molecularlevel.     

Estimation of spatial-temporal gait parameters in level walking based on a single accelerometer: Validation on normal subjects by standard gait analysis

This paper investigates the ability of a single wireless inertial sensing device stuck on the lower trunk to provide spatial-temporal parameters during level walking. The 3-axial acceleration signals were filtered and the timing of the main gait events identified. Twenty-two healthy subjects were analyzed with this system for validation, and the estimated parameters were compared with those obtained with state-of-the-art gait analysis, i.e. stereophotogrammetry and dynamometry. For each side, from four to six gait cycles were measured with the device, of which two were validated by gait analysis. The new acquisition system is easy to use and does not interfere with regular walking. No statistically significant differences were found between the acceleration-based measurements and the corresponding ones from gait analysis for most of the spatial-temporal parameters, i.e. stride length, stride duration, cadence and speed, etc.; significant differences were found for the gait cycle phases, i.e. single and double support duration, etc. The system therefore shows promise also for a future routine clinical use.     

Testing of "Venetian-Blind" silicon microstructures with optical methods

In this paper, we illustrate the design and testing of new silicon microstructures, fabricated by means of a conventional planar process. These "Venetian-blind" structures consist of arrays of narrow, rectangular suspended masses (width =31 /spl mu/m, length =400 /spl mu/m, thickness =15 /spl mu/m), which can be tilted using electrostatic actuation. Characterization of their static and dynamic behavior was performed with optical methods. The diffraction patterns in monochromatic light were analyzed and vibration measurements were performed by means of semiconductor laser feedback interferometry: experimental data on the tilt angle as a function of the applied voltage and on the resonance frequencies are reported. A maximum tilt angle of approximately 1.9/spl deg/ was obtained with a driving voltage in the range of 70-95 V. All the tested devices showed resonance frequencies higher than 80 kHz, which is fast enough (i.e., switching time in the millisecond range) for future use in optical interconnections. Numerical analyses were performed to evaluate the coupled electromechanical behavior of the microstructures, confirming the observed experimental behavior.     

Influence of current density on crystalline structure and magnetic properties of electrodeposited Co-rich CoNiW alloys

The influence of current density, at the interval 5–100 mA cm⁻², on the structural and magnetic properties of electrodeposited (Co_100−xNi_x)_100−yW_y alloys (x = 23–33.5 at. % Ni, y = 1.7–7.3 at. % W) was studied from a glycine-containing bath. W-content decreases with the increase of the current density magnitude. X-ray data have shown stabilization of hexagonal close packed, face centered cubic or a mixture of these structures by modulating the applied cathodic current density, for values lower than 50 mA cm⁻². Two structural phase transitions were observed: one from hexagonal close packed to face centered cubic structural transition occurring for a current density of 20 mA cm⁻², and another one, from cubic crystalline phase to amorphous state, which happens for values higher than 50 mA cm⁻². These structural phase transitions seem to be associated with the W-content as well as average crystalline grain sizes that reduce with increasing the current density value. The grain size effect may explain the face centered cubic stabilization in Co-rich CoNiW alloys, which was initially assumed to be basically due to H-adsorption/incorporation. Magnetic properties of Co-rich CoNiW alloys are strongly modified by the current density value; as a result of the changes on the W-content and their structural properties.     

On the oxy analogues to the 3 leads to 1 intramolecularly hydrogen-bonded peptide conformations

The possible occurrence of the oxy analogues to the 3 leads to 1 intramolecularly hydrogen-bonded peptide conformations (main feature of the gamma turn), recently proposed in solution by several authors, has been investigated in a number of N-tert-butyloxycarbonyl-alpha-amino acids by x-ray diffraction, infrared absorption, proton magnetic resonance, and circular dichroism techniques. These folded conformations are absent in the solid state in all cases so far examined; however, they seem to be present in solution, the extent of the population of these forms in the conformational equilibrium mixtures being solvent, temperature, and structure dependent. In the solid state N-tert-butyloxycarbonyl-D-valine has the urethane-CONH-group in the cis configuration; this is the first time such a configuration has been found in the solid-state for a secondary amide group in a linear compound.     

Removal of dissolved rhenium by sorption onto organic polymers: study of rhenium as an analogue of radioactive technetium

Technetium (99Tc) is one of the main components of nuclear wastes. Tc characteristics can be predicted by studying rhenium (75Re), one of its chemical analogue, thus avoiding the use of a radioactive element at high concentrations. The objectives of this experimental study was to understand the sorption behavior of Re with natural organic materials in order to define the possible condition of Tc uptake in case where Tc may be transferred into surface or ground waters. As the well-defined organic sorbents we chose chitosan which contains amine -NH2 groups; poly-galacturonic acid (PGA) and poly-styrene sulfonates (PSS) which contain respectively carboxyl -COOH and sulfonate -SO3H groups. Concerning the reaction of Re with PGA or with PSS, no interaction between Re and carboxyl or sulfonate groups was found within the detection limit of this study. Re sorption on chitosan was found to be dependent on ionic strength and pH. We propose that non-specific sorption of perrhenate ion ReO4- via electrostatic interaction takes place at the protonated amine groups NH3+. The polymer-solution interface can be described by the electric diffuse double layer model combined with the Langmuir-Freundlich model. The calculation is in good agreement with our experimental results.     

Globally convergent autocalibration using interval analysis

We address the problem of autocalibration of a moving camera with unknown constant intrinsic parameters. Existing autocalibration techniques use numerical optimization algorithms whose convergence to the correct result cannot be guaranteed, in general. To address this problem, we have developed a method where an interval branch-and-bound method is employed for numerical minimization. Thanks to the properties of interval analysis this method converges to the global solution with mathematical certainty and arbitrary accuracy and the only input information it requires from the user are a set of point correspondences and a search interval. The cost function is based on the Huang-Faugeras constraint of the essential matrix. A recently proposed interval extension based on Bernstein polynomial forms has been investigated to speed up the search for the solution. Finally, experimental results are presented.     

Bulk polymerization of acrylonitrile with electrochemically generated NO.3 radicals

The radical bulk polymerization of AN in HNO₃AN solutions was obtained through anodic formation of NO^.₃ radicals. The system exhibits a marked post-polymerization effect which extent depends on various factors. Low molecular weight products were also formed, expecially at high current densities. Both radical occlusion phenomena and formation of oligomers limit the monomer to polymer conversion.     

New Anacardic Acid‐Inspired Benzamides: Histone Lysine Acetyltransferase Activators

A series of N‐(4‐cyano‐3‐trifluoromethyl‐phenyl)‐2‐ethoxy‐6‐alkyl (and alkenyl) benzamides related to the anacardic acid derivative CTPB have been prepared from 2,6‐dihydroxybenzoic acid with a Suzuki coupling and addition of the anion of 4‐cyano‐3‐trifluoromethylphenylamine to a benzodioxinone as the key steps. In U937 cells, these analogues, in particular 7 c , 7 d , 7 f and 7 j , induced cell‐cycle arrest in the G1 phase, caused apoptosis in about 20 % of the cells, and increased the acetylation levels of H3. These activities correlate with the enzymatic activation of histone lysine acetyltransferases (KATs): CBP and PCAF.