Design of a grid service-based platform for in silico protein-ligand screenings

Grid computing offers the powerful alternative of sharing resources on a worldwide scale, across different institutions to run computationally intensive, scientific applications without the need for a centralized supercomputer. Much effort has been put into development of software that deploys legacy applications on a grid-based infrastructure and efficiently uses available resources. One field that can benefit greatly from the use of grid resources is that of drug discovery since molecular docking simulations are an integral part of the discovery process. In this paper, we present a scalable, reusable platform to choreograph large virtual screening experiments over a computational grid using the molecular docking simulation software DOCK. Software components are applied on multiple levels to create automated workflows consisting of input data delivery, job scheduling, status query, and collection of output to be displayed in a manageable fashion for further analysis. This was achieved using Opal OP to wrap the DOCK application as a grid service and PERL for data manipulation purposes, alleviating the requirement for extensive knowledge of grid infrastructure. With the platform in place, a screening of the ZINC 2,066,906 compound "drug-like" subset database against an enzyme's catalytic site was successfully performed using the MPI version of DOCK 5.4 on the PRAGMA grid testbed. The screening required 11.56 days laboratory time and utilized 200 processors over 7 clusters.     

Analysis of PD-generated SF/sub 6/ decomposition gases adsorbed on carbon nanotubes

Chemical byproducts analysis has been recognized as a powerful diagnosis method for SF₆ gas-insulated switchgear (GIS). The authors have previously demonstrated that a carbon nanotube (CNT) gas sensor could detect partial discharge (PD) generated in SF₆ gas. However, PD-generated decomposition gas species, which were responsible for the CNT gas sensor response, have not been identified yet. In this paper, two kinds of experiments were conducted in order to identify the responsible decomposition gas species. At first, the decomposition gas molecules adsorbed on CNTs were analyzed by Fourier transformation infrared (FTIR) spectroscopy. FTIR absorbance was observed around 735 cm^-1 after CNTs were exposed to PD generated in SF₆. In the second experiment, the CNT gas sensor responses to typical SF₆ decomposition products (HF and SF₄) were examined. The CNT gas sensor responded to these gases in the same way as to PD generated in SF₆. SF₄ response was larger than HF response. Based on these results, SF ₄ and SOF₂ emerged as candidates for the responsible decomposition gases. Electrochemical interactions between adsorbed gas molecules and CNT were discussed based on theoretical predictions of molecular orbital calculations. The calculation results suggested that both of SOF₂ and SF₄ could increase the CNT gas sensor conductance     

Magnetization Reversal by Electrical Spin Injection in Ferromagnetic (Ga,Mn)As-Based Magnetic Tunnel Junctions

We report current-induced magnetization reversal in a ferromagnetic semiconductor-based magnetic tunnel junction (Ga,Mn)As/AlAs/(Ga,Mn)As prepared by molecular beam epitaxy on a p-GaAs(001) substrate. A change in magneto-resistance that is asymmetric with respect to the current direction is found with the excitation current of 10⁶ A/cm². Contributions of both unpolarized and spin-polarized components are examined, and we conclude that the partial magnetization reversal occurs in the (Ga,Mn)As layer having smaller magnetization with the spin-polarized tunneling current of 10⁵ A/cm².     

Current-induced domain nucleation in ferromagnet

A key mechanism of the current-induced magnetization dynamics is the spin torque from a spin polarized current (spin current), which couples to spatial gradient of magnetization. Recently, it was pointed out that a large spin current applied to a uniform ferromagnet leads to a spin-wave instability. In this paper, we show that such instability is absent in a state containing a domain wall. This may indicate that nucleation of magnetic domains occurs above a certain critical spin current. This scenario is supported by an explicit energy comparison between the uniformly magnetized state and the domain-wall state under spin current.     

Calculations from texture of earing in deep drawing for FCC metal sheets

The present study aims to calculate the height at each peripheral position of a cup drawn from polycrystalline sheet using texture data. In the analytical treatment the polycrystalline sheet is simplified to an aggregation of many single crystals with various orientations, and the texture is represented by a three-dimensional crystallite orientation distribution function. The ear is calculated crystallographically using the orientation distribution function as a volume fraction of a certain oriented crystal. In the experiment aluminium, Al-Mg alloy and copper sheets which are treated under various conditions of cold rolling and heat treatment are used. The average textures over the thicknesses of the sheets are measured by the Schulz reflection method. The calculated ears based on the measured textures are compared with the experimental ears for each material. The results show that all the principal features of the ears of drawn cups are predicted satisfactorily by the calculation.     

MC180295 Inhibited Epstein–Barr Virus-Associated Gastric Carcinoma Cell Growth by Suppressing DNA Repair and the Cell Cycle

DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295, which was discovered by screening for demethylating agents. {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295. MKN28 cells infected with EBV were sensitive to {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 could up-regulate their expression. In conclusion, {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.     

Psychological Stress Exacerbates Inflammation of the Ileum via the Corticotropin-Releasing Hormone-Mast Cell Axis in a Mouse Model of Eosinophilic Enteritis

The effects of psychological stress on eosinophilic gastrointestinal disorders have not been elucidated. This study investigated the effects of psychological stress in a mouse model of eosinophilic enteritis (EoN). BALB/c mice were treated with ovalbumin (OVA) to create an EoN model and subjected to either water avoidance stress (WAS) or sham stress (SS). Microscopic inflammation, eosinophil and mast cell counts, mRNA expression, and protein levels of type 2 helper T cell (Th2) cytokines in the ileum were compared between groups. We evaluated ex vivo intestinal permeability using an Ussing chamber. A corticotropin-releasing hormone type 1 receptor (CRH-R1) antagonist was administered before WAS, and its effects were analyzed. WAS significantly increased diarrhea occurrence and, eosinophil and mast cell counts, and decreased the villus/crypt ratio compared to those in the SS group. The mRNA expression of CRH, interleukin IL-4, IL-5, IL-13, eotaxin-1, and mast cell tryptase β2 significantly increased, and the protein levels of IL-5, IL-13, and OVA-specific immunoglobulin E (IgE) also significantly increased in the WAS group. Moreover, WAS significantly increased the intestinal permeability. The CRH-R1 antagonist significantly inhibited all changes induced by WAS. Psychological stress exacerbated ileal inflammation via the CRH-mast cell axis in an EoN mouse model.     

Isolation and characterization of predominant microorganisms during decomposition of waste materials in a field-scale composter

A self-heating field-scale composter treating agro-industrial wastes within a period of 30 d was analyzed by denaturing gradient gel electrophoresis (DGGE) (Pedro et al., J. Biosci. Bioeng., 91, 159-165, 2001). Three major bands were derived from Propionibacterium acnes, Methylobacterium mesophilicum or M. radiotolerans, and Bacillus thermocloacae. Strains MSP09A and MSP06G with close affiliation to P. acnes and B. thermocloacae, respectively, were successfully isolated. Based on quantitative-PCR results, the relative population of MSP09A increased towards the end of the composting process (mesophilic stage) while MSP06G seemed to predominate during the middle period (thermophilic stage). These results correlated highly with their growth temperatures. MSP09A and MSP06G had different metabolic profiles which were largely affected by culture conditions. MSP09A was able to utilize large complex molecules of lipids and proteins. An interspecies relationship in terms of metabolites such as propionic acid was expected between the two microorganisms.