PosMed (Positional Medline): prioritizing genes with an artificial neural network comprising medical documents to accelerate positional cloning

PosMed (http://omicspace.riken.jp/) prioritizes candidate genes for positional cloning by employing our original database search engine GRASE, which uses an inferential process similar to an artificial neural network comprising documental neurons (or ‘documentrons’) that represent each document contained in databases such as MEDLINE and OMIM. Given a user-specified query, PosMed initially performs a full-text search of each documentron in the first-layer artificial neurons and then calculates the statistical significance of the connections between the hit documentrons and the second-layer artificial neurons representing each gene. When a chromosomal interval(s) is specified, PosMed explores the second-layer and third-layer artificial neurons representing genes within the chromosomal interval by evaluating the combined significance of the connections from the hit documentrons to the genes. PosMed is, therefore, a powerful tool that immediately ranks the candidate genes by connecting phenotypic keywords to the genes through connections representing not only gene–gene interactions but also other biological interactions (e.g. metabolite–gene, mutant mouse–gene, drug–gene, disease–gene and protein–protein interactions) and ortholog data. By utilizing orthologous connections, PosMed facilitates the ranking of human genes based on evidence found in other model species such as mouse. Currently, PosMed, an artificial superbrain that has learned a vast amount of biological knowledge ranging from genomes to phenomes (or ‘omic space’), supports the prioritization of positional candidate genes in humans, mouse, rat and Arabidopsis thaliana

Basic rockfall simulation with consideration of vegetation and application to protection measure

金沢大学理工研究域環境デザイン学系The estimation of risk due to rockfall is often done empirically. As a rational and effective method towards performance-based design of protection measures, a three-dimensional simulation method helps to describe the motion of rockfall on a slope and to consider the effect of vegetation probabilistically. This document details a typical simulation method and analyses the manner of rockfalls paired with interference of vegetation and other factors. As application, an actual slope is analyzed where rockfall occurred during the Noto Peninsula Earthquake. Finally, the validity and the benefits of the shown method are the basis for a hazard mapping for rockfall and the planning of measures

Characteristic Temperatures of Folding of a Small Peptide

We perform a generalized-ensemble simulation of a small peptide taking the interactions among all atoms into account. From this simulation we obtain thermodynamic quantities over a wide range of temperatures. In particular, we show that the folding of a small peptide is a multi-stage process associated with two characteristic temperatures, the collapse temperature T_{\theta} and the folding temperature T_f. Our results give supporting evidence for the energy landscape picture and funnel concept. These ideas were previously developed in the context of studies of simplified protein models, and here for the first time checked in an all-atom Monte Carlo simulation.Comment: Latex, 6 Figure

Basic rockfall simulation with consideration of vegetation and application to protection measure

The estimation of risk due to rockfall is often done empirically. As a rational and effective method towards performance-based design of protection measures, a three-dimensional simulation method helps to describe the motion of rockfall on a slope and to consider the effect of vegetation probabilistically. This document details a typical simulation method and analyses the manner of rockfalls paired with interference of vegetation and other factors. As application, an actual slope is analyzed where rockfall occurred during the Noto Peninsula Earthquake. Finally, the validity and the benefits of the shown method are the basis for a hazard mapping for rockfall and the planning of measures

Metropolis simulations of Met-Enkephalin with solvent-accessible area parameterizations

We investigate the solvent-accessible area method by means of Metropolis simulations of the brain peptide Met-Enkephalin at 300$K$. For the energy function ECEPP/2 nine atomic solvation parameter (ASP) sets are studied. The simulations are compared with one another, with simulations with a distance dependent electrostatic permittivity $\epsilon (r)$, and with vacuum simulations ($\epsilon =2$). Parallel tempering and the biased Metropolis techniques RM$_1$ are employed and their performance is evaluated. The measured observables include energy and dihedral probability densities (pds), integrated autocorrelation times, and acceptance rates. Two of the ASP sets turn out to be unsuitable for these simulations. For all other systems selected configurations are minimized in search of the global energy minima, which are found for the vacuum and the $\epsilon(r)$ system, but for none of the ASP models. Other observables show a remarkable dependence on the ASPs. In particular, we find three ASP sets for which the autocorrelations at 300$$K are considerably smaller than for vacuum simulations.Comment: 10 pages and 8 figure

The RIKEN integrated database of mammals

The RIKEN integrated database of mammals (http://scinets.org/db/mammal) is the official undertaking to integrate its mammalian databases produced from multiple large-scale programs that have been promoted by the institute. The database integrates not only RIKEN’s original databases, such as FANTOM, the ENU mutagenesis program, the RIKEN Cerebellar Development Transcriptome Database and the Bioresource Database, but also imported data from public databases, such as Ensembl, MGI and biomedical ontologies. Our integrated database has been implemented on the infrastructure of publication medium for databases, termed SciNetS/SciNeS, or the Scientists’ Networking System, where the data and metadata are structured as a semantic web and are downloadable in various standardized formats. The top-level ontology-based implementation of mammal-related data directly integrates the representative knowledge and individual data records in existing databases to ensure advanced cross-database searches and reduced unevenness of the data management operations. Through the development of this database, we propose a novel methodology for the development of standardized comprehensive management of heterogeneous data sets in multiple databases to improve the sustainability, accessibility, utility and publicity of the data of biomedical information

OmicBrowse: a Flash-based high-performance graphics interface for genomic resources

OmicBrowse is a genome browser designed as a scalable system for maintaining numerous genome annotation datasets. It is an open source tool capable of regulating multiple user data access to each dataset to allow multiple users to have their own integrative view of both their unpublished and published datasets, so that the maintenance costs related to supplying each collaborator exclusively with their own private data are significantly reduced. OmicBrowse supports DAS1 imports and exports of annotations to Internet site servers worldwide. We also provide a data-download named OmicDownload server that interactively selects datasets and filters the data on the selected datasets. Our OmicBrowse server has been freely available at http://omicspace.riken.jp/ since its launch in 2003. The OmicBrowse source code is downloadable from http://sourceforge.net/projects/omicbrowse/

Concerted nucleophilic aromatic substitution reactions

Recent developments in experimental and computational chemistry have identified a rapidly growing class of nucleophilic aromatic substitutions that proceed by concerted (cS NAr) rather than classical, two-step, S NAr mechanisms. Whereas traditional S NAr reactions require substantial activation of the aromatic ring by electron-withdrawing substituents, such activating groups are not mandatory in the concerted pathways

Konzertierte nukleophile aromatische Substitutionen

Jüngste Entwicklungen in der experimentellen und theoretischen Chemie haben zur Identifizierung einer schnell wachsenden Klasse von nukleophilen aromatischen Substitutionsreaktionen geführt, die einem konzertierten Mechanismus (cSNAr) folgen, und nicht dem klassischen, zweistufigen SNAr-Mechanismus. Während klassische SNAr-Reaktionen auf die substantielle Aktivierung des aromatischen Ringes durch elektronenziehende Substituenten angewiesen sind, ist eine solche Aktivierung für den konzertierten Reaktionsverlauf nicht zwingend nötig

Combined assessment of EGFR pathway-related molecular markers and prognosis of NSCLC patients

The purpose of this study is to evaluate the prognostic value of the combined assessment of multiple molecular markers related to the epidermal growth factor receptor (EGFR) pathway in resected non-small cell lung cancer (NSCLC) patients. Tumour specimens of 178 NSCLC patients were collected and analysed for EGFR and KRAS mutation status by DNA sequencing, and for EGFR copy number by fluorescent in situ hybridisation. Tissue microarrays were generated and used to determine the expression of multiple EGFR pathway-related proteins by immunohistochemistry. We analysed the association between each marker and patient prognosis. Univariate analyses for each clinical variable and each molecular marker were performed using Kaplan–Meier curves and log-rank tests. From these results, we selected the variables KRAS mutations and expression of cytoplasmic EGFR, granular pERK, nuclear pSTAT3, cytoplasmic E-cadherin and cytoplasmic pCMET to enter into a Cox proportional hazards model, along with stage as the strongest clinical variable related with prognosis. Of the EGFR-related markers evaluated here, the markers EGFR, pERK, pSTAT3, E-cadherin, pCMET and mutations in KRAS were associated with survival when analysed in combination in our patient cohort, with P=0.00015 as the P-value for a test of the additional impact of markers on prognosis, after taking stage into consideration. Confirmation of the impact of these markers in independent studies will be necessary