Using a homology model of cytochrome P450 2D6 to predict substrate site of metabolism

CYP2D6 is an important enzyme that is involved in first pass metabolism and is responsible for metabolizing ~25% of currently marketed drugs. A homology model of CYP2D6 was built using X-ray structures of ligand-bound CYP2C5 complexes as templates. This homology model was used in docking studies to rationalize and predict the site of metabolism of known CYP2D6 substrates. While the homology model was generally found to be in good agreement with the recently solved apo (ligand-free) X-ray structure of CYP2D6, significant differences between the structures were observed in the B′ and F–G helical region. These structural differences are similar to those observed between ligand-free and ligand-bound structures of other CYPs and suggest that these conformational changes result from induced-fit adaptations upon ligand binding. By docking to the homology model using Glide, it was possible to identify the correct site of metabolism for a set of 16 CYP2D6 substrates 85% of the time when the 5 top scoring poses were examined. On the other hand, docking to the apo CYP2D6 X-ray structure led to a loss in accuracy in predicting the sites of metabolism for many of the CYP2D6 substrates considered in this study. These results demonstrate the importance of describing substrate-induced conformational changes that occur upon binding. The best results were obtained using Glide SP with van der Waals scaling set to 0.8 for both the receptor and ligand atoms. A discussion of putative binding modes that explain the distribution of metabolic sites for substrates, as well as a relationship between the number of metabolic sites and substrate size, are also presented. In addition, analysis of these binding modes enabled us to rationalize the typical hydroxylation and O-demethylation reactions catalyzed by CYP2D6 as well as the less common N-dealkylation.     

Disordered network state in hydrated block-copolymer surfactants

Hydration of poly(butadiene-b-ethylene oxide) diblock copolymers leads to various ordered and disordered phases, analogous to the aqueous phase behavior of surfactants and lipids. Small-angle x-ray scattering measurements corroborated by cryogenic scanning electron microscopy imaging reveal a random network (N) morphology at polymer compositions and water content intermediate to those associated with ordered cylinders (H1) and lamellae (L). This sequence of self-assembled structures is strikingly similar to the phase behavior of certain water-oil-surfactant microemulsions.     

Variations of soil radon and thoron concentrations in a fault zone and prospective earthquakes in SW Taiwan

An automatic station for soil gas monitoring was set up on an active fault zone of SW Taiwan. After more than one year of continuous measurements, some spike-like anomalous high radon and thoron concentrations could be observed. A similar soil radon spectrum was also obtained from an independent monitoring station, which was only 100 m away. These anomalous peaks usually occurred a few days or weeks before the earthquakes (M_L4.5). This indicates that variations of both soil radon and thoron can serve as useful tools for earthquake surveillance, esp. at fault zones.     

Zernike moments and LDP-weighted patches for content-based image retrieval

This paper proposes a new algorithm using global and local features for content-based image retrieval. Global features are extracted using the magnitude of Zernike moments (ZMs). Local features are obtained through local directional pattern (LDP). Generally, LDP is used to extract texture-based features from an image. In this paper, LDP is used to encode both texture and shape information of an image to represent more meaningful features. To encode texture-based features, original image is used to compute the LDP features. To extract shape information from an image, dual-tree complex wavelet transform (DT-CWT) is applied on image which generates six directional wavelets. These six directional wavelets are superimposed in order to obtain shape-encoded image. LDP is then applied on this wavelet-based shape-encoded image. Further, to enhance retrieval accuracy, LDP features are extracted from patches of both original and shape-encoded images. These patches are assigned with weights based on average discrimination capability of features in a patch. Experiments are performed using three different standard databases with various variations such as pose, distortion, partial occlusion and complex structure. The proposed technique achieves 96.4 and 98.76 % retrieval accuracy at a recall of 50 %, for Kimia-99 and COIL-100 databases, respectively. For MPEG-7 CE-2 shape database, retrieval accuracy of 61.93 % is achieved in terms of average Bull’s eye performance (BEP). The proposed technique is also tested on Springer medical image database to explore its scope in other areas, wherein it attains average BEP of 69.68 % in comparison with 61.52 % with ZMs. It is observed that the proposed technique outperforms other well-known existing methods of image retrieval.     

Nanoscale Resistive Switching in Amorphous Perovskite Oxide (a‐SrTiO3) Memristors

Memristive devices are the precursors to high density nanoscale memories and the building blocks for neuromorphic computing. In this work, a unique room temperature synthesized perovskite oxide (amorphous SrTiO₃: a‐STO) thin film platform with engineered oxygen deficiencies is shown to realize high performance and scalable metal‐oxide‐metal (MIM) memristive arrays demonstrating excellent uniformity of the key resistive switching parameters. a‐STO memristors exhibit nonvolatile bipolar resistive switching with significantly high (10³–10⁴) switching ratios, good endurance (>10⁶I–V sweep cycles), and retention with less than 1% change in resistance over repeated 10⁵ s long READ cycles. Nano‐contact studies utilizing in situ electrical nanoindentation technique reveal nanoionics driven switching processes that rely on isolatedly controllable nano‐switches uniformly distributed over the device area. Furthermore, in situ electrical nanoindentation studies on ultrathin a‐STO/metal stacks highlight the impact of mechanical stress on the modulation of non‐linear ionic transport mechanisms in perovskite oxides while confirming the ultimate scalability of these devices. These results highlight the promise of amorphous perovskite memristors for high performance CMOS/CMOL compatible memristive systems.     

SERS from two-tier sphere segment void substrates

Sphere segment void, or inverse opal, films prepared from a variety of coinage metals have shown promise as reliable and reproducible substrates for surface enhanced Raman spectroscopy (SERS). Sphere segment void substrates are prepared from colloidal templates consisting of one or more layers of polystyrene spheres. In this paper, we investigate the reflection spectra and SERS for a gold film consisting of two-tiers of spherical cavities, and show that the best SERS enhancements are obtained from substrates consisting of just a single layer of sphere segment voids.     

Stimulated Raman scattering of gaussian laser beam in relativistic plasma

This paper presents an investigation of Stimulated Raman Scattering of gaussian laser beam in relativistic Plasma. The pump beam interacts with a pre-excited electron plasma wave and thereby generate a back-scattered wave. Due to intense laser beam, electron oscillatory velocity becomes comparable to the velocity of light, which modifies the background plasma density profile in a direction transverse to pump beam axis. The relativistic non-linearity due to increase in mass of the electrons effects the incident laser beam, electron plasma wave and back-scattered beam. We have set up the non-linear differential equations for the beam width parameters of the main beam, electron plasma wave, back-scattered wave and derived SRS back-reflectivity by taking full non-linear part of the dielectric constant of relativistic plasma with the help of moment theory approach. It is observed from the analysis that self-focusing of the pump beam greatly affects the SRS reflectivity, which plays a significant role in laser induced fusion.     

Self-focusing of Gaussian laser beam in collisionless plasma and its effect on stimulated Raman scattering process

This paper presents an investigation of self-focusing of Gaussian laser beam in collisionless plasma and its effect on stimulated Raman scattering process. The pump beam interacts with a pre-excited electron plasma wave thereby generating a back-scattered wave. On account of Gaussian intensity distribution of laser beam, the time independent component of the ponderomotive force along a direction perpendicular to the beam propagation becomes finite, which modifies the background plasma density profile in a direction transverse to pump beam axis. This modification in density affects the incident laser beam, electron plasma wave and back-scattered beam. We have set up the non-linear differential equations for the beam width parameters of the main beam, electron plasma wave, back-scattered wave and SRS-reflectivity by taking full non-linear part of the dielectric constant of collisionless plasma with the help of moment theory approach. It is observed from the analysis that focusing of waves greatly enhances the SRS reflectivity.     

Vibration analysis of axisymmetric functionally graded viscothermoelastic spheres简

The present study focuses on the analysis of free vibrations of axisymmetric functionally graded hollow spheres. The material is assumed to be graded in radial di- rection with a simple power law. Matrix Frrbenious method of extended power series is employed to derive the analytical solutions for displacement, temperature, and stresses. The dispersion relations for the existence of various types of pos- sible modes of vibrations in the considered hollow sphere are derived in a compact form. In order to explore the character- istics of vibrations, the secular equations are further solved by using fixed point iteration numerical technique with the help of MATLAB software. The numerical results have been presented graphically for polymethyl methecrylate materials in respect of natural frequencies, frequency shift, inverse quality factor, displacement, temperature change, and radial stress.