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GENEVESTIGATOR. Arabidopsis microarray database and analysis toolbox.

High-throughput gene expression analysis has become a frequent and powerful research tool in biology. At present, however, few software applications have been developed for biologists to query large microarray gene expression databases using a Web-browser interface. We present GENEVESTIGATOR, a database and Web-browser data mining interface for Affymetrix GeneChip data. Users can query the database to retrieve the expression patterns of individual genes throughout chosen environmental conditions, growth stages, or organs. Reversely, mining tools allow users to identify genes specifically expressed during selected stresses, growth stages, or in particular organs. Using GENEVESTIGATOR, the gene expression profiles of more than 22,000 Arabidopsis genes can be obtained, including those of 10,600 currently uncharacterized genes. The objective of this software application is to direct gene functional discovery and design of new experiments by providing plant biologists with contextual information on the expression of genes. The database and analysis toolbox is available as a community resource at https://www.genevestigator.ethz.ch.

Arabidopsis↗

Using the Web to aid biochemists and microbiologists: an example of computer-based learning using PCR as an example.

The aim of this study was two-fold: to make available to the medical community a fast, efficient tool for troubleshooting PCR problems, and to demonstrate that hypermedia allow one to approach this kind of problem in a new, more useful way. The Web provides access to an enormous amount of information in the medical area, and in particular enables troubleshooting of new techniques in the medical laboratory. Currently it is possible to find textual information but it is not always easy to find hypermedia information. In many cases authors change only the means of dissemination of a book or paper to the Web, but do not adapt the information to the features of this new medium. The prototype of our hypermedia application was developed using Director and Flash programs (Macromedia), the application was developed from a decision tree built as a result of information compiled from expert PCR users and the existing literature. It was implemented on a website using Dreamweaver (Macromedia). The usefulness and possibilities of this application have been tested with physicians, medical laboratory technicians, and health science students, and have been proven to be more effective than traditional methods, both in education processes and in helping researchers and medical laboratory technicians in their daily work. The advance and popularization of the Internet in the medical profession requires information on the Web to adapt to the advantages offered by hypermedia. This new step must be taken, and the Web must offer medical users not only a different medium of information distribution but also a new way of handling and obtaining information.

Biochemistry↗

Cross-reactivity of Sydney funnel-web spider antivenom: neutralization of the in vitro toxicity of other Australian funnel-web (Atrax and Hadronyche) spider venoms.

Australian funnel-web spiders are recognized as one of the most venomous spiders to humans world-wide. Funnel-web spider antivenom (FWS AV) reverses clinical effects of envenomation from the bite of Atrax robustus and a small number of related Hadronyche species. This study assessed the in vitro efficacy of FWS AV in neutralization of the effects of funnel-web spider venoms, collected from various locations along the eastern seaboard of Australia, in an isolated chick biventer cervicis nerve-muscle preparation. Venoms were separated by SDS-PAGE electrophoresis to compare protein composition and transblotted for Western blotting and incubation with FWS AV.SDS-PAGE of venoms revealed similar low and high molecular weight protein bands. Western blotting with FWS AV showed similar antivenom binding with protein bands in all the venoms tested. Male funnel-web spider venoms (7/7) and female venoms (5/10) produced muscle contracture and fasciculation when applied to the nerve-muscle preparation. Venom effects were reversed by subsequent application of FWS AV or prevented by pretreatment of the preparation with antivenom.FWS AV appears to reverse the in vitro toxicity of a number of funnel-web spider venoms from the eastern seaboard of Australia. FWS AV should be effective in the treatment of envenomation from most, if not all, species of Australian funnel-web spiders.

Antivenins↗

The Tropical Biominer Project: mining old sources for new drugs.

The Tropical Biominer Project is a recent initiative from the Federal University of Minas Gerais (UFMG) and the Oswaldo Cruz foundation, with the participation of the Biominas Foundation (Belo Horizonte, Minas Gerais, Brazil) and the start-up Homologix. The main objective of the project is to build a new resource for the chemogenomics research, on chemical compounds, with a strong emphasis on natural molecules. Adopted technologies include the search of information from structured, semi-structured, and non-structured documents (the last two from the web) and datamining tools in order to gather information from different sources. The database is the support for developing applications to find new potential treatments for parasitic infections by using virtual screening tools. We present here the midpoint of the project: the conception and implementation of the Tropical Biominer Database. This is a Federated Database designed to store data from different resources. Connected to the database, a web crawler is able to gather information from distinct, patented web sites and store them after automatic classification using datamining tools. Finally, we demonstrate the interest of the approach, by formulating new hypotheses on specific targets of a natural compound, violacein, using inferences from a Virtual Screening procedure.

Animals↗

A cost-effective web-based teaching file system.

Teaching files are common in radiology. Although there is an increasing role of digital technology in radiology departments, today's teaching files have not yet seen the application of this new technology. This may have been due in part to poor or incomplete implementation in many commercial software packages. We have demonstrated that by utilizing free software from the Internet, a web-based teaching file system, which is easy to use, low cost, and secure, can be created.

Cost-Benefit Analysis↗

Integrating multiple clinical information systems using the Java Message Service framework.

This article describes an application for capturing, delivering, and tracking urgent radiology exam results. Urgent exam findings are entered using a Web form embedded within the Picture archiving and communication system (PACS) display station. The findings are then accessible via soft copy using the PACS display stations, hospital information system (HIS) terminals, or wireless-enabled personal digital assistants (PDAs) or via hard copy printouts that are generated automatically or on demand. Additionally, quality control is performed on those findings entered by radiology residents and fellows, the results of which are used for both performance tracking and educational activities. The application was developed using Sun Microsystems' Java programming language. The Java Message Service (JMS) was used to manage the delivery of findings. JMS provides a robust, flexible framework for exchanging messages between disparate applications. The application is now used for all urgent exams; completely replacing the original paper-based system. The use of JMS provides the necessary level of reliability needed by this application.

Computer Communication Networks↗

Incorporating genetic analyses into birth defects cluster investigations: strategies for identifying candidate genes.

BACKGROUND: Incorporating genetic analyses into birth defect cluster investigations may increase understanding of both genetic and environmental risk factors for the defect. Current constraints of most birth defect cluster investigations make candidate gene selection the most feasible approach. Here, we describe strategies for choosing candidate genes for such investigations, which will also be applicable to more general gene-environment studies. METHODS: We reviewed publicly available web-based resources for selection of candidate genes and identification of risk factors, as well as publications on different strategies for candidate gene selection. RESULTS: Candidate gene selection requires consideration of available gene-disease databases, previous epidemiological studies, animal model research, linkage and expression studies, and other resources. We describe general considerations for utilizing available resources, as well as provide an example of a search for candidate genes related to gastroschisis. CONCLUSIONS: Available web resources could facilitate selection of candidate genes, but selection of optimal candidates will still require a strong understanding of genetics and the pathogenesis of the defect, as well as careful consideration of previous epidemiological studies.

Animals↗

Large-scale plant protein subcellular location prediction.

Current plant genome sequencing projects have called for development of novel and powerful high throughput tools for timely annotating the subcellular location of uncharacterized plant proteins. In view of this, an ensemble classifier, Plant-PLoc, formed by fusing many basic individual classifiers, has been developed for large-scale subcellular location prediction for plant proteins. Each of the basic classifiers was engineered by the K-Nearest Neighbor (KNN) rule. Plant-PLoc discriminates plant proteins among the following 11 subcellular locations: (1) cell wall, (2) chloroplast, (3) cytoplasm, (4) endoplasmic reticulum, (5) extracell, (6) mitochondrion, (7) nucleus, (8) peroxisome, (9) plasma membrane, (10) plastid, and (11) vacuole. As a demonstration, predictions were performed on a stringent benchmark dataset in which none of the proteins included has > or =25% sequence identity to any other in a same subcellular location to avoid the homology bias. The overall success rate thus obtained was 32-51% higher than the rates obtained by the previous methods on the same benchmark dataset. The essence of Plant-PLoc in enhancing the prediction quality and its significance in biological applications are discussed. Plant-PLoc is accessible to public as a free web-server at: (http://202.120.37.186/bioinf/plant). Furthermore, for public convenience, results predicted by Plant-PLoc have been provided in a downloadable file at the same website for all plant protein entries in the Swiss-Prot database that do not have subcellular location annotations, or are annotated as being uncertain. The large-scale results will be updated twice a year to include new entries of plant proteins and reflect the continuous development of Plant-PLoc.

Plant Proteins↗

Digital photography: a primer for pathologists.

The computer and the digital camera provide a unique means for improving hematology education, research, and patient service. High quality photographic images of gross specimens can be rapidly and conveniently acquired with a high-resolution digital camera, and specialized digital cameras have been developed for photomicroscopy. Digital cameras utilize charge-coupled devices (CCD) or Complementary Metal Oxide Semiconductor (CMOS) image sensors to measure light energy and additional circuitry to convert the measured information into a digital signal. Since digital cameras do not utilize photographic film, images are immediately available for incorporation into web sites or digital publications, printing, transfer to other individuals by email, or other applications. Several excellent digital still cameras are now available for less than 2,500 dollars that capture high quality images comprised of more than 6 megapixels. These images are essentially indistinguishable from conventional film images when viewed on a quality color monitor or printed on a quality color or black and white printer at sizes up to 11x14 inches. Several recent dedicated digital photomicroscopy cameras provide an ultrahigh quality image output of more than 12 megapixels and have low noise circuit designs permitting the direct capture of darkfield and fluorescence images. There are many applications of digital images of pathologic specimens. Since pathology is a visual science, the inclusion of quality digital images into lectures, teaching handouts, and electronic documents is essential. A few institutions have gone beyond the basic application of digital images to developing large electronic hematology atlases, animated, audio-enhanced learning experiences, multidisciplinary Internet conferences, and other innovative applications. Digital images of single microscopic fields (single frame images) are the most widely utilized in hematology education at this time, but single images of many adjacent microscopic fields can be stitched together to prepare "zoomable" panoramas that encompass a large part of a microscope slide and closely simulate observation through a real microscope. With further advances in computer speed and Internet streaming technology, the virtual microscope could easily replace the real microscope in pathology education. Later in this decade, interactive immersive computer experiences may completely revolutionize hematology education and make the conventional lecture and laboratory format obsolete. Patient care is enhanced by the transmission of digital images to other individuals for consultation and education, and by the inclusion of these images in patient care documents. In research laboratories, digital cameras are widely used to document experimental results and to obtain experimental data.

Computers↗

[Effective literature searching. Focusing the question and using PubMed queries].

Apart from clinical and social expertise, the availability of contemporary knowledge is a key component in organisations within the health system that aim for excellence and competitiveness. Efficient literature searching is within this context a core business of evidence-based medicine. In addition to the need for valid data, the retrieval of information based on published literature has so far constituted a critical hurdle. Based on these requirements, two core issues for success with respect to literature searching are described: First, the generation of a structured question to form the basis of the most promising search terms. Second, a new feature of the web service of the national library of medicine, called "clinical queries", that allows the application of predefined filters to allocate clinically relevant data in terms of published clinical trials and systematic reviews.

Evidence-Based Medicine↗

Inflammatory models of cutaneous hyperalgesia are sensitive to effects of ibuprofen in man.

A new experimental procedure was developed to quantify the analgesic actions of non-steroidal anti-inflammatory drugs (NSAIDs) in healthy human subjects. In order to mimic the clinical situation, the drug was 'therapeutically' administered 1 day after induction of inflammation by freezing a small skin area. The procedure was easily tolerated and led to a marked hyperalgesia without ongoing pain which was tested using mechanical impact stimulation and magnitude estimation. For comparison, we used a previously established model of repeated noxious pinching of an interdigital skin web which induces a hyperalgesia to pressure (rated via visual analogue scale), and topical application of capsaicin which leads to quantifiable flare and allodynia responses. The effects of a cumulative drug regime of ibuprofen in 2 different doses (3 x 400 mg and 3 x 800 mg at 2-h intervals) were tested versus placebo using a double-blind cross-over design with 24 volunteers of either gender. Ibuprofen caused a significant suppression of the hyperalgesia to repeated pinching and of the hyperalgesia to impact stimulation following freeze trauma. In contrast, there was no effect on the areas of flare and allodynia induced by capsaicin application and on the impact evoked sensations from untreated skin. The two dosages of ibuprofen, however, appeared to be equally effective in a way that suggests a plateauing of the antihyperalgesic effect. The two models in which hyperalgesia is affected by ibuprofen, i.e., repeated pinching and impact stimulation after freeze trauma, seem to provide comparable sensitivity. The freeze model may in the future have the advantage to allow for a better temporal resolution of the drug's action profile.

Adult↗

Factors influencing involvement in research and career choice: a survey of graduating physical medicine and rehabilitation residents.

OBJECTIVE: To assess the extent to which physical medicine and rehabilitation (PM&R) residents' involvement in research and selection of postgraduate practice may be related to residency program research requirements and support for presentations. DESIGN: Internet-based survey. SETTING: Anonymous access to Web form. PARTICIPANTS: PM&R residents graduating in June 2004 and 2005. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Involvement in research, postgraduate practice setting and planned research effort, residency research requirement, and support for scientific presentations. RESULTS: One hundred sixty (24%) of the 657 graduating residents, representing 25 states, the District of Columbia, and Puerto Rico, responded. Eighty-five percent indicated research involvement, with 74% reporting a research requirement and 85% residency program financial support for presentations. On average, respondents planned to devote 7% (95% confidence interval, 5%-9%) of their time to research once in practice. There was a statistically significant association between the existence of a research requirement and involvement in research (P < .001). However, there was no evidence of a statistically significant association between either the existence of a research requirement or presentation support and the selection of an academic career. There were no significant regional disparities for the existence of a research requirement, travel support, or number of presentations. However, there was a statistically significant regional difference in the proportion of postgraduate practice time that the respondents planned to devote to research. CONCLUSIONS: A requirement for PM&R residents to be involved in research may influence research activity during residency but may not be associated with selection of an academic or research-oriented practice.

Adult↗

RIKEN mouse genome encyclopedia.

We have been working to establish the comprehensive mouse full-length cDNA collection and sequence database to cover as many genes as we can, named Riken mouse genome encyclopedia. Recently we are constructing higher-level annotation (Functional ANnoTation Of Mouse cDNA; FANTOM) not only with homology search based annotation but also with expression data profile, mapping information and protein-protein database. More than 1,000,000 clones prepared from 163 tissues were end-sequenced to classify into 159,789 clusters and 60,770 representative clones were fully sequenced. As a conclusion, the 60,770 sequences contained 33,409 unique. The next generation of life science is clearly based on all of the genome information and resources. Based on our cDNA clones we developed the additional system to explore gene function. We developed cDNA microarray system to print all of these cDNA clones, protein-protein interaction screening system, protein-DNA interaction screening system and so on. The integrated database of all the information is very useful not only for analysis of gene transcriptional network and for the connection of gene to phenotype to facilitate positional candidate approach. In this talk, the prospect of the application of these genome resourced should be discussed. More information is available at the web page: http://genome.gsc.riken.go.jp/.

Animals↗

Morphology of necrosis and repair after transcoronary ethanol ablation of septal hypertrophy.

The transcoronary ethanol ablation of septum hypertrophy (TASH) results in a necrosis of the myocardium. In contrast to the ischemically induced necrosis, there is not any phagocytosis caused by leukocytes and macrophages, nor does transformation into granulation tissue occur. Even six months after the application of ethanol, the myofibrils can be identified as "ghost cells" surrounded by a web of collagen fibers. This special forming of a scar, unknown to this day, is documented by 13 patients who died between 25 minutes and two years after ethanol-induced ablation of the hypertrophic septum in hypertrophic obstructive cardiomyopathiy (HOCM).

Adult↗

PROBEmer: A web-based software tool for selecting optimal DNA oligos.

PROBEmer (http://probemer.cs.loyola.edu) is a web-based software tool that enables a researcher to select optimal oligos for PCR applications and multiplex detection platforms including oligonucleotide microarrays and bead-based arrays. Given two groups of nucleic-acid sequences, a target group and a non-target group, the software identifies oligo sequences that occur in members of the target group, but not in the non-target group. To help predict potential cross hybridization, PROBEmer computes all near neighbors in the non-target group and displays their alignments. The software has been used to obtain genus-specific prokaryotic probes based on the 16S rRNA gene, gene-specific probes for expression analyses and PCR primers. In this paper, we describe how to use PROBEmer, the computational methods it employs, and experimental results for oligos identified by this software tool.

Algorithms↗

Online handwritten script recognition.

Automatic identification of handwritten script facilitates many important applications such as automatic transcription of multilingual documents and search for documents on the Web containing a particular script. The increase in usage of handheld devices which accept handwritten input has created a growing demand for algorithms that can efficiently analyze and retrieve handwritten data. This paper proposes a method to classify words and lines in an online handwritten document into one of the six major scripts: Arabic, Cyrillic, Devnagari, Han, Hebrew, or Roman. The classification is based on 11 different spatial and temporal features extracted from the strokes of the words. The proposed system attains an overall classification accuracy of 87.1 percent at the word level with 5-fold cross validation on a data set containing 13,379 words. The classification accuracy improves to 95 percent as the number of words in the test sample is increased to five, and to 95.5 percent for complete text lines consisting of an average of seven words.

Algorithms↗

Accurate and automated classification of protein secondary structure with PsiCSI.

PsiCSI is a highly accurate and automated method of assigning secondary structure from NMR data, which is a useful intermediate step in the determination of tertiary structures. The method combines information from chemical shifts and protein sequence using three layers of neural networks. Training and testing was performed on a suite of 92 proteins (9437 residues) with known secondary and tertiary structure. Using a stringent cross-validation procedure in which the target and homologous proteins were removed from the databases used for training the neural networks, an average 89% Q3 accuracy (per residue) was observed. This is an increase of 6.2% and 5.5% (representing 36% and 33% fewer errors) over methods that use chemical shifts (CSI) or sequence information (Psipred) alone. In addition, PsiCSI improves upon the translation of chemical shift information to secondary structure (Q3 = 87.4%) and is able to use sequence information as an effective substitute for sparse NMR data (Q3 = 86.9% without (13)C shifts and Q3 = 86.8% with only H(alpha) shifts available). Finally, errors made by PsiCSI almost exclusively involve the interchange of helix or strand with coil and not helix with strand (<2.5 occurrences per 10000 residues). The automation, increased accuracy, absence of gross errors, and robustness with regards to sparse data make PsiCSI ideal for high-throughput applications, and should improve the effectiveness of hybrid NMR/de novo structure determination methods. A Web server is available for users to submit data and have the assignment returned.

Automation↗