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[Integration of metabolic data by positron emission tomography in image-guided neurosurgical interventions].

The potential of positron emission tomography (PET) to investigate accurately in vivo pathophysiology has opened new perspectives for the management of neurological disorders, especially brain tumors. Integration of PET in the management of brain tumors represents a unique way to provide metabolic and functional information that can be used for diagnosis, guidance of therapies, and treatment monitoring. We have developed a stereotactic method allowing the routine integration of PET images in neurosurgical procedures with a high precision. Our ten year experience with the use of PET in stereotactic conditions for neurosurgical guidance, indicates that PET integration in image-guide neurosurgical approaches, including [1] stereotactic biopsy, [2] neuronavigation and [3] radiosurgery with Leksell Gamma Knife, is feasible and worthwhile, in that it provides complementary information that contribute to the optimization of the neurosurgical treatment of brain tumors.

Biopsy↗

All systems go: launching cell simulation fueled by integrated experimental biology data.

Biological simulation serves to unify the basic elements of systems biology, namely, model selection, experimentation and model refinement. To select biochemical models for simulation, metabolome analysis can be performed using capillary electrophoresis or liquid chromatography coupled with mass spectrometry. In this manner, selected models can be elaborated with temporal/spatial gene and protein expression data obtained from model organisms such as Escherichia coli. The E. coli single gene deletion mutant library (KO collection) and His-tag/GFP-fusion single open reading frame clone expression library (ASKA) are powerful resources for this task. The integration of parallel experimental datasets into dynamic simulation tools forms the remaining challenge for the systematic analysis and elucidation of biological networks and holds promise for biotechnological applications.

Cell Physiological Phenomena↗

Techniques for optimization of queries on integrated biological resources.

Today, scientific data are inevitably digitized, stored in a wide variety of formats, and are accessible over the Internet. Scientific discovery increasingly involves accessing multiple heterogeneous data sources, integrating the results of complex queries, and applying further analysis and visualization applications in order to collect datasets of interest. Building a scientific integration platform to support these critical tasks requires accessing and manipulating data extracted from flat files or databases, documents retrieved from the Web, as well as data that are locally materialized in warehouses or generated by software. The lack of efficiency of existing approaches can significantly affect the process with lengthy delays while accessing critical resources or with the failure of the system to report any results. Some queries take so much time to be answered that their results are returned via email, making their integration with other results a tedious task. This paper presents several issues that need to be addressed to provide seamless and efficient integration of biomolecular data. Identified challenges include: capturing and representing various domain specific computational capabilities supported by a source including sequence or text search engines and traditional query processing; developing a methodology to acquire and represent semantic knowledge and metadata about source contents, overlap in source contents, and access costs; developing cost and semantics based decision support tools to select sources and capabilities, and to generate efficient query evaluation plans.

Algorithms↗

GeneWays: a system for extracting, analyzing, visualizing, and integrating molecular pathway data.

The immense growth in the volume of research literature and experimental data in the field of molecular biology calls for efficient automatic methods to capture and store information. In recent years, several groups have worked on specific problems in this area, such as automated selection of articles pertinent to molecular biology, or automated extraction of information using natural-language processing, information visualization, and generation of specialized knowledge bases for molecular biology. GeneWays is an integrated system that combines several such subtasks. It analyzes interactions between molecular substances, drawing on multiple sources of information to infer a consensus view of molecular networks. GeneWays is designed as an open platform, allowing researchers to query, review, and critique stored information.

Artificial Intelligence↗

Integrating biomonitoring exposure data into the risk assessment process: phthalates [diethyl phthalate and di(2-ethylhexyl) phthalate] as a case study.

The probability of nonoccupational exposure to phthalates is high given their use in a vast range of consumables, including personal care products (e.g., perfumes, lotions, cosmetics), paints, industrial plastics, and certain medical devices and pharmaceuticals. Phthalates are of high interest because of their potential for human exposure and because animal toxicity studies suggest that some phthalates affect male reproductive development apparently via inhibition of androgen biosynthesis. In humans, phthalates are rapidly metabolized to their monoesters, which can be further transformed to oxidative products, conjugated, and eliminated. Phthalate metabolites have been used as biomarkers of exposure. Using urinary phthalate metabolite concentrations allows accurate assessments of human exposure because these concentrations represent an integrative measure of exposure to phthalates from multiple sources and routes. However, the health significance of this exposure is unknown. To link biomarker measurements to exposure, internal dose, or health outcome, additional information (e.g., toxicokinetics, inter- and intraindividual differences) is needed. We present a case study using diethyl phthalate and di(2-ethylhexyl) phthalate as examples to illustrate scientific approaches and their limitations, identify data gaps, and outline research needs for using biomonitoring data in the context of human health risk assessment, with an emphasis on exposure and dose. Although the vast and growing literature on phthalates research could not be covered comprehensively in this article, we made every attempt to include the most relevant publications as of the end of 2005.

Animals↗

Human cellular protein patterns and their link to genome DNA mapping and sequencing data: towards an integrated approach to the study of gene expression.

Analysis of cellular protein patterns by computer-aided two-dimensional gel electrophoresis together with recent advances in protein sequence analysis and expression systems have made possible the establishment of comprehensive two-dimensional gel protein databases that may link protein and DNA mapping and sequence information and that offer an integrated approach to the study of gene expression. With the integrated approach offered by two-dimensional gel protein databases it is now possible to reveal phenotype-specific protein(s), to microsequence them, to search for homology with previous identified proteins, to clone the cDNAs, to assign partial protein sequences to genes for which the full DNA sequence and the chromosome location are known, and to study the regulatory properties and function of groups of proteins that are coordinately expressed in a given biological process. Comprehensive two-dimensional gel protein databases will provide an integrated picture of the expression levels and properties of the thousands of protein components of organelles, pathways, and cytoskeletal systems, both under physiological and abnormal conditions, and are expected to lead to the identification of new regulatory networks. So far, about 20% (600 out of 2,980) of the total number of proteins recorded in the human keratinocyte protein database have been identified and we are actively gathering qualitative and quantitative biological data on all resolved proteins. Given the current improvements on microsequencing as well as the availability of specific antibodies, it seems feasible to expect that most known keratinocyte proteins will be identified in the very near future. This feast will reveal a wealth of new proteins that will become amenable to experimentation both at the biochemical and molecular biology level.

Amino Acid Sequence↗

The EBI SRS server-new features.

MOTIVATION: Here we report on recent developments at the EBI SRS server (http://srs.ebi.ac.uk). SRS has become an integration system for both data retrieval and sequence analysis applications. The EBI SRS server is a primary gateway to major databases in the field of molecular biology produced and supported at EBI as well as European public access point to the MEDLINE database provided by US National Library of Medicine (NLM). It is a reference server for latest developments in data and application integration. The new additions include: concept of virtual databases, integration of XML databases like the Integrated Resource of Protein Domains and Functional Sites (InterPro), Gene Ontology (GO), MEDLINE, Metabolic pathways, etc., user friendly data representation in 'Nice views', SRSQuickSearch bookmarklets. AVAILABILITY: SRS6 is a licensed product of LION Bioscience AG freely available for academics. The EBI SRS server (http://srs.ebi.ac.uk) is a free central resource for molecular biology data as well as a reference server for the latest developments in data integration.

Computer Communication Networks↗

A new combined integral-light and slit-scan data analysis system (DAS) for flow cytometry.

Flow cytometry using list mode parameters such as fluorescence emission, light scatter and size on one hand and different slit-scan parameters on the other hand needs a fast, flexible, efficient and easy-to-use data analysis software. A new software package (data analysis system, DAS) has been developed that integrates data analysis for conventional (integral-light) flow cytometry and for slit-scan flow cytometry. The requirements, design and some examples are discussed and an implementation for IBM-compatible computers is presented. Special attention is directed to the handling of different data types from one-parameter histograms to multiparameter slit-scan data files. The package can be used as an interpreting programming language or as an interactive menu-driven command line interpreter with a large number of graphic, mathematical and statistical functions. DAS is not limited to use in flow cytometry only, but multidimensional data analysis, from astronomy to economics, can be done as well.

Data Display↗

IntegratedMap: a Web interface for integrating genetic map data.

SUMMARY: IntegratedMap is a Web application and database schema for storing and interactively displaying genetic map data. Its Web interface includes a menu for direct chromosome/linkage group selection, a search form for selection based on mapped object location and linkage group displays. An overview display provides convenient access to the full range of mapped and anchored object types with genetic locus details, such as numbers, types and names of mapped/anchored objects displayed in a compact scrollable list box that automatically updates based on selected map location and object type. Also, multilinkage group and localized map views are available along with links that can be configured for integration with other Web resources. AVAILABILITY: IntegratedMap is implemented in C#/ASP.NET and the package, including a MySQL schema creation script, is available from http://cggc.agtec.uga.edu/Data/download.asp

Algorithms↗

ARCADIA: a system for the integration of angiocardiographic data and images by an object-oriented DBMS.

Use of data base techniques to store medical records has been going on for more than 40 years. Some aspects still remain unresolved, e.g., the management of textual data and image data within a single system. Object-orientation techniques applied to a database management system (DBMS) allow the definition of suitable data structures (e.g., to store digital images): some facilities allow the use of predefined structures when defining new ones. Currently available object-oriented DBMS, however, still need improvements both in the schema update and in the query facilities. This paper describes a prototype of a medical record that includes some multimedia features, managing both textual and image data. The prototype here described considers data from the medical records of patients subjected to percutaneous transluminal coronary artery angioplasty. We developed it on a Sun workstation with a Unix operating system and ONTOS as an object-oriented DBMS.

Angiocardiography↗

Interpreter of maladies: redescription mining applied to biomedical data analysis.

Comprehensive, systematic and integrated data-centric statistical approaches to disease modeling can provide powerful frameworks for understanding disease etiology. Here, one such computational framework based on redescription mining in both its incarnations, static and dynamic, is discussed. The static framework provides bioinformatic tools applicable to multifaceted datasets, containing genetic, transcriptomic, proteomic, and clinical data for diseased patients and normal subjects. The dynamic redescription framework provides systems biology tools to model complex sets of regulatory, metabolic and signaling pathways in the initiation and progression of a disease. As an example, the case of chronic fatigue syndrome (CFS) is considered, which has so far remained intractable and unpredictable in its etiology and nosology. The redescription mining approaches can be applied to the Centers for Disease Control and Prevention's Wichita (KS, USA) dataset, integrating transcriptomic, epidemiological and clinical data, and can also be used to study how pathways in the hypothalamic-pituitary-adrenal axis affect CFS patients.

Algorithms↗

CGO: utilizing and integrating gene expression microarray data in clinical research and data management.

Clinical GeneOrganizer (CGO) is a novel windows-based archiving, organization and data mining software for the integration of gene expression profiling in clinical medicine. The program implements various user-friendly tools and extracts data for further statistical analysis. This software was written for Affymetrix GeneChip *.txt files, but can also be used for any other microarray-derived data. The MS-SQL server version acts as a data mart and links microarray data with clinical parameters of any other existing database and therefore represents a valuable tool for combining gene expression analysis and clinical disease characteristics.

Computational Biology↗

Integrating base rate data in violence risk assessments at capital sentencing.

Prediction of violence in capital sentencing has been controversial. In the absence of a scientific basis for risk assessment, mental health professionals offering opinions in the capital sentencing context are prone to errors. Actuarial or group statistical data, known as base rates, have proven far superior to other methods for reducing predictive errors in many contexts, including risk assessment. Actuarial follow-up data on violent recidivism of capital murderers in prison and post release have been compiled and analyzed to demonstrate available base rates for use by mental health experts conducting risk assessments pertaining to capital sentencing. This paper also reviews various methods for individualizing the application of base rates to specific cases.

Actuarial Analysis↗

SMART-PET: multimodality white matter imaging and display without loss of quantitative information.

PURPOSE: To improve analysis of cerebral white matter (WM) in fluoro-deoxy-glucose positron emission tomography (PET) images. MATERIALS AND METHODS: A multimodality analysis technique (segmented MRI and registered Talairach-transformed PET [SMART-PET]) was used for quantitative assessment of WM metabolism. Data processing included Talairach transformation of three-dimensional magnetic resonance imaging (MRI) and subsequent automated segmentation and coregistration to normalized PET images. Color model transformations were used for combined display: the hue saturation value color model was regarded as a three-dimensional data matrix, integrating quantitative voxel data of both modalities. The technique was applied in normal subjects and in patients suffering from different WM diseases. Regional analysis was performed to classify metabolic impairment on a five-point scale. RESULTS: Using SMART-PET, a considerable gain in image contrast for WM was achieved in all cases. In the normal subjects, WM metabolism was shown to be homogeneously unimpaired. Sum scores of regional analysis revealed metabolic WM changes in all patients. Extent of WM hypometabolism exceeded the extent of the lesions as delineated by MRI signal changes. CONCLUSION: The potential of the method for further elucidation of the role of WM diseases in brain dysfunction in patients is discussed.

Brain↗

Polyadipates used as plasticizers in food contact: fraction below 1000 Da determined by size exclusion chromatography with evaporative light scattering detection and segmental response linearization or UV detection.

Polyadipates might be a suitable replacement for conventional plasticizers in plastisols to produce lids for glass jars complying with legal limits for oily foods. For the characterization of polyadipates, the proportion of the material with a molecular mass below 1000 Da is important. Determination of the material < 1000 Da is also important for checking compliance with the specific legal limit. The analytical problems and the sources of uncertainty are investigated. Even when calibrated with constituents of polyadipates, preseparation at 1000 Da is of limited accuracy, since stretched and cyclic components of the same molecular mass have different retention times; a compromise must be found. UV detection leaves substantial uncertainty as the response particularly of the < 1000 Da components varies and tends to be below that of the higher molecular mass polyadipates. Evaporative light scattering detection has a nonlinear response for which a segmental correction (linearization of the integration raw data) is suggested: The raw data of the integration is linearized by an exponential function before the chromatogram is reconstructed.

Journal Article↗

Scaling up population dynamics: integrating theory and data.

How to scale up from local-scale interactions to regional-scale dynamics is a critical issue in field ecology. We show how to implement a systematic approach to the problem of scaling up, using scale transition theory. Scale transition theory shows that dynamics on larger spatial scales differ from predictions based on the local dynamics alone because of an interaction between local-scale nonlinear dynamics and spatial variation in density or the environment. Based on this theory, a systematic approach to scaling up has four steps: (1) derive a model to translate the effects of local dynamics to the regional scale, and to identify key interactions between nonlinearity and spatial variation, (2) measure local-scale model parameters to determine nonlinearities at local scales, (3) measure spatial variation, and (4) combine nonlinearity and variation measures to obtain the scale transition. We illustrate the approach, with an example from benthic stream ecology of caddisflies living in riffles. By sampling from a simulated system, we show how collecting the appropriate data at local (riffle) scales to measure nonlinearities, combined with measures of spatial variation, leads to the correct inference for dynamics at the larger scale of the stream. The approach provides a way to investigate the mechanisms and consequences of changes in population dynamics with spatial scale using a relatively small amount of field data.

Animals↗