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ET viewer: an application for predicting and visualizing functional sites in protein structures.

SUMMARY: The Evolutionary Trace Viewer (ETV) provides a one-stop environment in which to run, visualize and interpret Evolutionary Trace (ET) predictions of functional sites in protein structures. ETV is implemented using Java to run across different operating systems using Java Web Start technology. AVAILABILITY: The ETV is available for download from our website at http://mammoth.bcm.tmc.edu/traceview/index.html. This webpage also links to sample trace results and a user manual that describes ET Viewer functions in detail.

Amino Acid Sequence↗

osni.info-Using free/libre/open source software to build a virtual international community for open source nursing informatics.

Many health informatics organizations seem to be slow to take up the advantages of dynamic, web-based technologies for providing services to, and interaction with, their members; these are often the very technologies they promote for use within healthcare environments. This paper aims to introduce some of the many free/libre/open source (FLOSS) applications that are now available to develop interactive websites and dynamic online communities as part of the structure of health informatics organizations, and to show how the Open Source Nursing Informatics Working Group (OSNI) of the special interest group in nursing informatics of the International Medical Informatics Association (IMIA-NI) is using some of these tools to develop an online community of nurse informaticians through their website, at . Some background introduction to FLOSS applications is used for the benefit of those less familiar with such tools, and examples of some of the FLOSS content management systems (CMS) being used by OSNI are described. The experiences of the OSNI will facilitate a knowledgeable nursing contribution to the wider discussions on the applications of FLOSS within health and healthcare, and provides a model that many other groups could adopt.

Database Management Systems↗

The future of 'pure' medical science: the need for a new specialist professional research system.

Over recent decades, medical research has become mostly an 'applied' science which implicitly aims at steady progress by an accumulation of small improvements, each increment having a high probability of validity. Applied medical science is, therefore, a social system of communications for generating pre-publication peer-reviewed knowledge that is ready for implementation. However, the need for predictability makes modern medical science risk-averse and this is leading to a decline in major therapeutic breakthroughs where new treatments for new diseases are required. There is need for the evolution of a specialized professional research system of pure medial science, whose role would be to generate and critically evaluate radically novel and potentially important theories, techniques, therapies and technologies. Pure science ideas typically have a lower probability of being valid, but the possibility of much greater benefit if they turn out to be true. The domination of medical research by applied criteria means that even good ideas from pure medical science are typically ignored or summarily rejected as being too speculative. Of course, radical and potentially important ideas may currently be published, but at present there is no formal mechanism by which pure science publications may be received, critiqued, evaluated and extended to become suitable for 'application'. Pure medical science needs to evolve to constitute a typical specialized scientific system of formal communications among a professional community. The members of this putative profession would interact via close research groupings, journals, meetings, electronic and web communications--like any other science. Pure medical science units might arise as elite grouping linked to existing world-class applied medical research institutions. However, the pure medical science system would have its own separate aims, procedures for scientific evaluation, institutional organization, funding and support arrangements; and a separate higher-professional career path with distinctive selection criteria. For instance, future leaders of pure medical science institutions would need to be selected on the basis of their specialized cognitive aptitudes and their record of having generated science-transforming ideas, as well as their research management skills. Pure medical science would work most effectively and efficiently if practiced in many independent and competing institutions in several different countries. The main 'market' for pure medical science would be the applied medical scientists, who need radical strategies to solve problems which are not yielding to established methods. The stimulus to create such elite pure medical science institutions might come from the leadership of academic 'entrepreneurs' (for instance, imaginative patrons in the major funding foundations), or be triggered by a widespread public recognition of the probable exhaustion of existing applied medical science approaches to solving major therapeutic challenges.

Biomedical Research↗

Configuring for the World Wide Web: recommendations for dermatologists.

Physicians have become increasingly interested in obtaining the hardware, software, and connection necessary to take advantage of the educational and practice material available on the World Wide Web (WWW) (i.e., on the Internet). The related ongoing development of unique on-line resources promises to provide a compelling force for change in the way in which information is accessed and medicine is practiced. WWW applications created for dermatologists often include high-quality images, and proper viewing is critical to use this information. Because images tend to be large files, and dermatology resources tend to have from several up to hundreds of images, the speed of transfer and display and the quality of the display are important factors to consider. This study was an evaluation of some of the current options in the hardware, software, and Internet connections to determine desirable configurations for accessing image-rich, on-line dermatology WWW applications.

Computer Communication Networks↗

Characterization of platelet-activating factor-induced cytosolic calcium mobilization in human eosinophils.

BACKGROUND: Activated eosinophils play an important role in the pathogenesis of bronchial asthma and other allergic diseases, and platelet-activating factor (PAF) is a potent activator of eosinophils. OBJECTIVE: To characterize the cytosolic Ca2+ ([Ca2+]i) mobilization in human eosinophils in response to PAF. METHODS: [Ca2+]i responses to PAF were examined in human eosinophils using a microscopic fura-2 fluorescence-ratio imaging system. RESULTS: PAF caused a significant and dose-dependent increase in (Ca2+)i, which consisted of an initial rapid rise followed by a sustained elevation. This PAF-induced (Ca2+)i rise was inhibited by WEB 2086, a specific PAF receptor antagonist. The addition of 5 mM EGTA or 1 mM Ni2+ to a nominally Ca2+-free solution did not appreciably reduce the initial rise but significantly inhibited the sustained rise. The application of a protein kinase C inhibitor, Ro31-8220, augmented the sustained increase by PAF. Thapsigargin, a microsomal Ca2+ ATPase inhibitor, induced no appreciable change in a nominally Ca2+-free solution but induced a marked increase in (Ca2+)i when changed to a Ca2+-containing solution. CONCLUSIONS: The initial rapid rise and the following sustained rise in (Ca2+)i by PAF depends on Ca2+ release from the intracellular Ca2+ stores and Ca2+ influx, respectively, which are regulated by protein kinase C in human eosinophils. Furthermore, the so called Ca2+-capacitative entry is possibly involved in the Ca2+ influx from the extracellular solution in human eosinophils.

Calcium Signaling↗

Community of Communities: an electronic link to integrating cultural diversity in nursing curriculum.

The inclusion of principles of diversity in nursing education has yet to reach expected levels of common understanding and value. Integration of human diversity is an expected outcome based on essentials for professional nursing education by the American Association of Colleges of Nursing. This article describes one approach that used electronic networking to integrate cultural diversity content into a graduate nursing curriculum. Regional networking among schools of nursing about cultural diversity resulted in the Community of Communities (COC) web page. The COC is a common electronic network that contains information and case studies based on a cultural assessment model. Modules in on-line courses are linked to a cultural module in the COC. Several applications are described herein. The COC modules were evaluated to determine if participants gained knowledge and insight into another culture. Findings suggested that students perceived that the COC modules increased the awareness culture plays in health care.

Community Health Nursing↗

L/D Protein Ligand Database (PLD): additional understanding of the nature and specificity of protein-ligand complexes.

SUMMARY: The Protein Ligand Database (PLD) is a publicly available web-based database that aims to provide further understanding of protein-ligand interactions. The PLD contains biomolecular data including calculated binding energies, Tanimoto ligand similarity scores and protein percentage sequence similarities. The database has potential for application as a tool in molecular design. AVAILABILITY: http://www-mitchell.ch.cam.ac.uk/pld/

Amino Acid Sequence↗

Towards pathogenomics: a web-based resource for pathogenicity islands.

Pathogenicity islands (PAIs) are genetic elements whose products are essential to the process of disease development. They have been horizontally (laterally) transferred from other microbes and are important in evolution of pathogenesis. In this study, a comprehensive database and search engines specialized for PAIs were established. The pathogenicity island database (PAIDB) is a comprehensive relational database of all the reported PAIs and potential PAI regions which were predicted by a method that combines feature-based analysis and similarity-based analysis. Also, using the PAI Finder search application, a multi-sequence query can be analyzed onsite for the presence of potential PAIs. As of April 2006, PAIDB contains 112 types of PAIs and 889 GenBank accessions containing either partial or all PAI loci previously reported in the literature, which are present in 497 strains of pathogenic bacteria. The database also offers 310 candidate PAIs predicted from 118 sequenced prokaryotic genomes. With the increasing number of prokaryotic genomes without functional inference and sequenced genetic regions of suspected involvement in diseases, this web-based, user-friendly resource has the potential to be of significant use in pathogenomics. PAIDB is freely accessible at http://www.gem.re.kr/paidb.

Bacteria↗

Application of in silico positional cloning and bioinformatic mutation analysis to the study of eye diseases.

A vast amount of DNA and protein sequence is now available and a plethora of programs have been developed to analyse the data. The bewildering variety of analyses that can be performed via the World-Wide Web can deter researchers from applying bioinformatics to augment their traditional genetic research. Focusing on the inherited eye diseases, this paper provides a guide to the appropriate software required for identification of candidate genes through to the detection and analysis of mutations.

Chromosome Mapping↗

[Nursing on the Web: the creation and validation process of a web site on coronary artery disease].

The World Wide Web is an important health information research source. A challenge for the Brazilian Nursing Informatics area is to use its potential to promote health education. This paper aims to present a developing and validating model used in an educational Web site, named CardioSite, which subject is Coronary Heart Disease. In its creation it was adopted a method with phases of conceptual modeling, development, implementation, and evaluation. In the evaluation phase, the validation was performed through an online informatics and health experts panel. The results demonstrated that information was reliable and valid. Considering that national official systems are not available to that approach, this model demonstrated effectiveness in assessing the quality of the Web site content.

Coronary Disease↗

ChroCoLoc: an application for calculating the probability of co-localization of microarray gene expression.

UNLABELLED: With the production of whole genome microarray chips the ability arises to investigate whether the regulation of particular groups of genes may be influenced by their chromosomal localization. Chromosome Co-Localization probability calculator (ChroCoLoc) is a publicly available web-based tool for the analysis of co-localization of co-expressed genes identified by microarray experiments. AVAILABILITY: http://www.ebi.ac.uk/expressionprofiler/

Algorithms↗

Intranet health clinic: Web-based medical support services employing XML.

In this paper, the implementation of an Internet-based telematic service for medical support is presented, which operates in pilot form within the INTRANET HEALTH CLINIC project--a two-year project supported by the European Commission under the Health Telematics Programme. The aim of the application is to offer high quality care to users of health services over inexpensive communication pathways, using Internet-based, interactive communication tools, like remote access to medical records and transmission of multimedia information. The XML technology was employed to achieve customised views on patient data, according to the access rights of different users. Strict security and access control policy were implemented to ensure secure transmission of medical data through the Internet. The system is designed to collaborate with existing clinical patient record systems and to be adjustable to different medical applications. Current pilot implementations are under clinical evaluation and include oncological patients (Greece), Lupus Erythrematosis (Canada), Obstetrics (Belgium) and Chronic Obstructive Pulmonary disease (Spain).

Computer Communication Networks↗

A local adhesive finger splint.

A new design of a local static finger splint is proposed. The splint is made by enveloping a length of wire into double-sided adhesive tape. The skin of the region to be immobilized is covered with an adhesive skin dressing, to which the splint is then adhered. This method of attachment gives more freedom in choosing a site of splint application and prevents access obstruction to the wound, blocking of tactile areas, and circulation impairment. The splint is light, low profile, and malleable at ambient temperature. The adhesive splint was used in 5 patients to maintain the first web space open or to immobilize stiff interphalangeal joints in flexion overnight.

Adhesives↗

Multi-query sequence BLAST output examination with MuSeqBox.

SUMMARY: MuSeqBox is a program to parse BLAST output and store attributes of BLAST hits in tabular form. The user can apply a number of selection criteria to filter out hits with particular attributes. MuSeqBox provides a powerful annotation tool for large sets of query sequences that are simultaneously compared against a database with any of the standard stand-alone or network-client BLAST programs. We discuss such application to the problem of annotation and analysis of EST collections. AVAILABILITY: The program was written in standard C++ and is freely available to noncommercial users by request from the authors. The program is also available over the web at http://bioinformatics.iastate.edu/bioinformatics2go/mb/MuSeqBox.html.

Alternative Splicing↗

Effects of stroma-free hemoglobin solutions on pulmonary vascular resistance and mediator release in the isolated perfused rabbit lung.

The aim of this study was to evaluate the effect of an ultrapure bovine stroma-free hemoglobin (SFH) on pulmonary vascular resistance and mediator release and to analyze potential mechanisms of action in the isolated perfused rabbit lung model. Repetitive bolus applications of small amounts of bovine SFH were examined which resulted in a reproducible acute increase of pulmonary vascular resistance of approx. 9 mmHg (controls, n = 6). It was tested whether the platelet-activating factor (PAF) antagonist WEB 2086 (50 microM; n = 6), the cyclooxygenase blocker diclofenac (10 micrograms/ml; n = 6), the iron-chelating agent deferoxamine (500 micrograms/ml, n = 6) and the radical scavenger catalase (5000 U/ml; n = 6) exert a protective effect on vasoconstrictor response to SFH. The pressure increase was completely suppressed in the lungs pretreated with WEB 2086, whereas diclofenac, deferoxamine and catalase failed to inhibit the vasoconstriction due to SFH. No significant differences in either TXB2 generation or in histamine release were found in the WEB 2086 group compared with untreated lungs. The results point towards the crucial role of PAF in mediation of vasoconstrictor side effects due to SFH.

Animals↗

Computational identification of residues that modulate voltage sensitivity of voltage-gated potassium channels.

BACKGROUND: Studies of the structure-function relationship in proteins for which no 3D structure is available are often based on inspection of multiple sequence alignments. Many functionally important residues of proteins can be identified because they are conserved during evolution. However, residues that vary can also be critically important if their variation is responsible for diversity of protein function and improved phenotypes. If too few sequences are studied, the support for hypotheses on the role of a given residue will be weak, but analysis of large multiple alignments is too complex for simple inspection. When a large body of sequence and functional data are available for a protein family, mature data mining tools, such as machine learning, can be applied to extract information more easily, sensitively and reliably. We have undertaken such an analysis of voltage-gated potassium channels, a transmembrane protein family whose members play indispensable roles in electrically excitable cells. RESULTS: We applied different learning algorithms, combined in various implementations, to obtain a model that predicts the half activation voltage of a voltage-gated potassium channel based on its amino acid sequence. The best result was obtained with a k-nearest neighbor classifier combined with a wrapper algorithm for feature selection, producing a mean absolute error of prediction of 7.0 mV. The predictor was validated by permutation test and evaluation of independent experimental data. Feature selection identified a number of residues that are predicted to be involved in the voltage sensitive conformation changes; these residues are good target candidates for mutagenesis analysis. CONCLUSION: Machine learning analysis can identify new testable hypotheses about the structure/function relationship in the voltage-gated potassium channel family. This approach should be applicable to any protein family if the number of training examples and the sequence diversity of the training set that are necessary for robust prediction are empirically validated. The predictor and datasets can be found at the VKCDB web site.

Algorithms↗

Using education to promote research dissemination in nursing.

In order to maintain the highest standards of care, nurses need to be aware of the most recent and relevant research and use this to inform their practice. However, this is often difficult because of both the limited time available in which to access research and the need for advanced critical appraisal skills. Further, given the overload of complex research information, nurses may be overwhelmed by the extent of available research. This paper describes a unique approach, the Web Resource Appraisal Process (WRAP), for integrating research and education by directly engaging nurses undertaking postgraduate studies in the review of existing research as it is applied to the contemporary workplace. In so doing, experienced nurses investigate the application of research to practice by actively engaging in research dissemination, communication, and education. By engaging in this process, nurses generate new knowledge based on the integration of current research with their practice experience, while simultaneously gaining the benefits of experiential learning.

Communication↗

Interactive educational diabetes simulators: future possibilities.

In 1996 an interactive educational diabetes simulator called AIDA was released without charge on the Internet as a non-commercial contribution to continuing diabetes education. Over the past 3 years over 30,000 people have visited the AIDA Web site-- http://www.diabetic.org.uk/aida.htm--and over 10,000 copies of the program have been downloaded from there free-of-charge. This review builds on the experience gained from the AIDA development and the World Wide Web distribution of the software, and looks to the future, highlighting features which users might expect to see in future generations of such interactive educational diabetes programs. Novel functions already described in the literature are overviewed, and possible applications using personal computers and the Internet are discussed. The importance of the user interface is stressed. The concept of a "virtual diabetic patient" that provides an electronic representation of a patient with diabetes--and which can be used for self-learning/teaching/demonstration purposes--is highlighted.

Blood Glucose↗