Binding conformation prediction between human acetylcholinesterase and cytochrome c using molecular modeling methods

The acetylcholinesterase (AChE) is important to terminate acetylcholine-mediated neurotransmission at cholinergic synapses. The pivotal role of AChE in apoptosome formation through the interactions with cytochrome c (Cyt c) was demonstrated in recent study. In order to investigate the proper binding conformation between the human AChE (hAChE) and human Cyt c (hCyt c), macro-molecular docking simulation was performed using DOT 2.0 program. The hCyt c was bound to peripheral anionic site (PAS) on hAChE and binding mode of the docked conformation was very similar to the reported crystal structure of the AChE and fasciculin-II (Fas-II) complex. Two 10ns molecular dynamics (MD) simulations were carried out to refine the binding mode of docked structure and to observe the differences of the binding conformations between the absent (Apo) and presence (Holo) of heme group. The key hydrogen bonding residues between hAChE and hCyt c proteins were found in Apo and Holo systems, as well as each Tyr341 and Trp286 residue of hAChE was participated in cation-pi (π) interactions with Lys79 of hCyt c in Apo and Holo systems, respectively. From the present study, although the final structures of the Apo and Holo systems have similar binding pattern, several differences were investigated in flexibilities, interface interactions, and interface accessible surface areas. Based on these results, we were able to predict the reasonable binding conformation which is indispensable for apoptosome formation.     

Synthesis and characterization of novel blue azo‐dye derivatives containing acrylate group for dye‐based color filters

Abstract— Even though dyes have a fine resolution and good chromaticities, they are not widely used as coloring materials for color filters (CFs) due to their low thermal stability and chemical resistance. A series of azo‐dye derivatives, which consist of two cross‐linkable acrylate or methacrylate groups to improve thermal and chemical properties, have been synthesized and used to fabricate color filters. The spectral properties and chemical/thermal stabilities of the fabricated CFs were investigated by comparing dye‐based CFs, without a complicated dispersion process, but with pigment‐based CFs using dispersed pigment. Also, more properties including the development test and surface morphologies lithographic properties were studied. The synthesized azo dyes were characterized by elemental analysis, UV‐visible spectra, IR, mass, and ¹H‐NMR spectra.     

Web-based algorithm for cylindricity evaluation using support vector machine learning

This paper introduces a cylindricity evaluation algorithm based on support vector machine learning with a specific kernel function, referred to as SVR, as a viable alternative to traditional least square method (LSQ) and non-linear programming algorithm (NLP). Using the theory of support vector machine regression, the proposed algorithm in this paper provides more robust evaluation in terms of CPU time and accuracy than NLP and this is supported by computational experiments. Interestingly, it has been shown that the SVR significantly outperforms LSQ in terms of the accuracy while it can evaluate the cylindricity in a more robust fashion than NLP when the variance of the data points increases. The robust nature of the proposed algorithm is expected because it converts the original nonlinear problem with nonlinear constraints into other nonlinear problem with linear constraints. In addition, the proposed algorithm is programmed using Java Runtime Environment to provide users with a Web based open source environment. In a real-world setting, this would provide manufacturers with an algorithm that can be trusted to give the correct answer rather than making a good part rejected because of inaccurate computational results.     

Multi-objective FMS process planning with various flexibilities using a symbiotic evolutionary algorithm

This paper presents an evolutionary algorithm, called the multi-objective symbiotic evolutionary algorithm (MOSEA), to solve a multi-objective FMS process planning (MFPP) problem with various flexibilities. The MFPP problem simultaneously considers four types of flexibilities related to machine, tool, sequence, and process and takes into account three objectives: balancing the machine workload, minimizing part movements, and minimizing tool changes. The MOSEA is modeled as a two-leveled structure to find a set of well-distributed solutions close to the true Pareto optimal solutions. To promote the search capability of such solutions, two main processes imitating symbiotic evolution and endosymbiotic evolution are introduced, together with an elitist strategy and a fitness sharing scheme. Evolutionary components suitable for the MFPP problem are provided. With a variety of test-bed problems, the performance of the proposed MOSEA is compared with those of existing multi-objective evolutionary algorithms. The experimental results show that the MOSEA is promising in solution convergence and diversity.     

A kernel free particle‐finite element method for hypervelocity impact simulation

An improved hybrid particle‐finite element method has been developed for the simulation of hypervelocity impact problems. Unlike alternative methods, the revised formulation computes the density without reference to any kernel or interpolation functions, for either the density or the rate of dilatation. This simplifies the state space model and leads to a significant reduction in computational cost. The improved method introduces internal energy variables as generalized co‐ordinates in a new formulation of the thermomechanical Lagrange equations. Example problems show good agreement with exact solutions in one dimension and good agreement with experimental data in a three‐dimensional simulation. Copyright © 2005 John Wiley & Sons, Ltd.     

Cardiac autonomic nerve function and insulin sensitivity in obese subjects

OBJECTIVE: To investigate whether obesity influences cardiac autonomic nerve function. DESIGN: Comparing two groups of subjects with different degrees of obesity to normal weight controls. SUBJECTS: 19 healthy controls (mean age 33 y, BMI 21.7 +/- 0.2 kg/m2) and 17 obese non-diabetic subjects (mean age 39 y, BMI 33.7 +/- 1.8 kg/m2). MEASUREMENTS: Insulin sensitivity was calculated by an oral glucose tolerance test. Autonomic nerve function was evaluated by analysing the variation of the heart frequency at rest (coefficient variation of R-R intervals, REST 1), during deep respiration, at a Valsalva maneuver (longest/shortest R-R interval during inspiration hold) and by the Ewing test (ratio between the 30th and 15th R-R interval after reaching up-right position). RESULTS: The obese showed a lower insulin sensitivity than healthy controls (3.09 vs 4.60 mg x l2/mmol x mU x min, P < 0.001). Their variation in heart frequency was reduced (REST 1: 1.95 vs 2.9, P < 0.01, Valsalva: 1.30 vs 1.52 and Ewing test: 1.03 vs 1.14, P < 0.05). However, patients with moderate (BMI 31.7 kg/m2) or severe obesity (39.0 kg/m2) with identical insulin sensitivity had no significant difference in autonomic nerve function. Except for the Ewing test all measured parameters for the evaluation of cardiac autonomic nerve function correlated with the degree of diminished insulin sensitivity (REST 1: r = 0.475, P < 0.001). CONCLUSION: Moderate obesity with significantly decreased insulin sensitivity is associated with impaired cardiac autonomic nerve function.     

Development of a biodegradable sirolimus-eluting stent coated by ultrasonic atomizing spray

In this study, poly(D,L lactic-co-glycolic acid) (PLGA) was used as a drug carrier to generate two types of stents loaded with different concentrations of sirolimus. These stents were prepared by ultrasonic atomizing spray coating. Ultrasonic atomizing spray nozzle uses a low-pressure air/gas to produce a soft, highly focused beam of small spray drops. An isolated hypotube delivers liquid to the nozzle's atomizing surface while air/gas, delivered through the nozzle orifice at a fixed low pressure, shapes the atomized drops into a very precise, targeted spray. The stent was moved both in the traverse direction and rotated during the spraying process. The morphology of the sirolimus-eluting stents was examined by scanning electron microscopy (SEM) which indicated that the coating was very smooth and uniform. The coating was found to have the ability to withstand the compressive and tensile strains imparted without cracking during the stent inflation process. Release profile of sirolimus was measured by high performance liquid chromatography (HPLC). The release behavior of sirolimus from the stent surface had a two phase release profile with a burst release period of about 2 days, followed by a sustained and slow release phase. The mass loss behavior of PLGA appeared linear throughout most of the degradation period. At 28 days, neointimal formation was found to be significantly decreased for both sirolimus-eluting stents as compared to bare-metal stents (BMS). Assessment of vascular healing revealed an absence of increased inflammation in both sirolimus-eluting stents. Inflammation is commonly observed in drug-eluting stents (DES) with nonbiodegradable polymeric coatings. Taking these results into account, these novel sirolimus-eluting stents may be good candidates to resolve in-stent restenosis.     

Dieless drawing steel wires using a dielectric heating method and modeling the process dynamics

Modern industries require the production of multi-functional, inorganic, micron-sized metal wires. This study suggests a novel method that could potentially offer a highly efficient dieless drawing technology for manufacturing thin stainless steel fibers. The method is based on a hot-working principle, using microwaves as the heat source and SiC as the susceptor. Experimental trials with a laboratory rig showed that the new system worked effectively for drawing the stainless steel wires and should be able to realize the diameter attenuation with a diameter reduction of up to 21%. The theoretical model describing the deformation behavior of the stainless steel wires in the working zone along with the constitutive equation of Bingham model modified with a power law and Zener–Hollomon parameter turned out to match very good with the actual results of the experiment. The coefficient of variation of the drawn wire diameter increased, as the draw ratio increased, which could be attributed to the occurrence of the narrow necking zone.     

Glycosidase inhibitory phenolic compounds from the seed of Psoralea corylifolia

The seeds of Psoralea corylifolia were extracted into five different polar solvents: chloroform, 50% ethanol in water, ethanol, methanol and water. All extracts were evaluated for glycosidase inhibitory activity. The chloroform extract (CE) showed the lowest IC₅₀ values against α-glucosidase (82.9 μg/ml) and α-mannosidase (132 μg/ml). Chromatography of CE yielded nine phenolic compounds which were identified as isovabachalcone (1), 4′-O-methylbavachalcone (2), isobavachromene (3), corylifolin (4), bavachinin (5), psoralidin (6), neobavaisoflavone (7), corylifol A (8), and bakuchiol (9). All isolated compounds, apart from compound 5, possessed α-glucosidase inhibitory activities. Among them, compounds 6–8 exhibited potent inhibition with IC₅₀s of 13.7, 27.7 and 11.3 μM, respectively. Furthermore, compounds 2 and 6 showed α-mannosidase inhibitory activity. Mechanistic analysis of their inhibition modes against α-glucosidase showed that compounds (6 and 7) were noncompetitive, whereas compound 8 was mixed. Furthermore, the most active glycosidase inhibitors (2, 6–8) were proven to be present in the native seed in high quantities by an HPLC chromatogram.