Arachidonic acid-induced calcium signalling in human airway smooth muscle cells

Until now computer-assisted parasite identification was based on database applications requiring data specification on an individual basis, thus limiting the ability of the system to handle rule-based knowledge as humans are used to do. A new Expert PArasite IdentificatiON (EPAION: Greek term for expert) system was developed to serve as an interface between the database and the user, where the database is a repository for bionomic and morphological facts about the parasites for the expert system. The system was developed by using a logic-based computer language which allows the definition of rules and facts to assist the creation of queries to the database. The components of the system are the knowledge base, the multimedia data base, the inference mechanism, and the graphical user interface. The operational modules of the system are the Parasite Identifier and the system Utilities. This expert system facilitates knowledge incorporation in a manner simulating the natural mental process, thus allowing the checking of the accuracy of the information that the user feeds to the computer and the creation of intelligent queries to the database. These characteristics accelerate focusing and optimize the parasite identification scheme regardless of the user's profile of competency.     

Machanism of the stimulatory effect of intracerebroventricular administration of histamine on gastatric acid secretion induced by pentagastrin in rats

MOTIVATION: We needed an efficient way to explore the binding reactions leading to protein complexes of known composition and structure. RESULTS: A new program is described that allows the user to define a set of protein elements and to link these elements into an oligomeric 'ball-and-stick' assembly in a graphical interface. Once the structure of the oligomer has been defined, the program then employs a novel algorithm to deduce the binding reactions and intermediate complexes needed to make the oligomer from its starting protein components. The program also finds the equilibrium state of the system, using either default starting concentrations and Kd values or data supplied by the user.     

MACROS: Multiobjective Automated Construction Resource Optimization System

This paper presents the development of a practical and automated system for optimizing the utilization of construction resources to simultaneously minimize project cost and duration while maximizing project quality. The system is named the Multiobjective Automated Construction Resource Optimization System (MACROS), and it incorporates four newly developed modules: (1) a multiobjective optimization module to quantify and optimize the impact of resource utilization decisions on construction duration, cost, and quality; (2) a relational database module to facilitate the storage and retrieval of construction scheduling and optimization data; (3) a middleware module to provide seamless integration between the internal modules in MACROS and external commercially available project management software; and (4) a user interface module to facilitate the input of project data and the visualization and ranking of the generated optimal construction plans. An example project of 180 activities is analyzed to illustrate the use of MACROS and demonstrate its unique and practical construction optimization capabilities.     

HOMSTRAD: a database of protein structure alignments for homologous families

We describe a database of protein structure alignments for homologous families. The database HOMSTRAD presently contains 130 protein families and 590 aligned structures, which have been selected on the basis of quality of the X-ray analysis and accuracy of the structure. For each family, the database provides a structure-based alignment derived using COMPARER and annotated with JOY in a special format that represents the local structural environment of each amino acid residue. HOMSTRAD also provides a set of superposed atomic coordinates obtained using MNYFIT, which can be viewed with a graphical user interface or used for comparative modeling studies. The database is freely available on the World Wide Web at: http://www-cryst.bioc.cam. ac.uk/-homstrad/, with search facilities and links to other databases.     

RNA secondary structure as a reusable interface to biological information resources

The dissemination of biological information has become critically dependent on the Internet and World Wide Web (WWW), which enable distributed access to information in a platform independent manner. The mode of interaction between biologists and on-line information resources, however, has been mostly limited to simple interface technologies such has hypertext links, tables and forms. The introduction of platform-independent runtime environments facilitates the development of more sophisticated WWW-based user interfaces. Until recently, most such interfaces have been tightly coupled to the underlying computation engines, and not separated as reusable components. We believe that many subdisciplines of biology have intuitive and familiar graphical representations of knowledge that can serve as multipurpose user interface elements. We call such graphical idioms "domain graphics". In order to illustrate the power of such graphics, we have built a reusable interface based on the standard two dimensional (2D) layout of RNA secondary structure. The interface can be used to represent any pre-computed layout of RNA, and takes as a parameters the sets of actions to be performed as a user interacts with the interface. It can provide to any associated application program information about the base, helix, or subsequence selected by the user. We show the versatility of this interface by using it as a special purpose interface to BLAST, Medline and the RNA MFOLD search/compute engines. These demonstrations are available at: http://www-smi.stanford.edu/projects/helix/pubs/ gene-combis-96/     

Intelligent Medical Record--entry (IMR-E)

This paper describes an automated medical record designed to allow providers to enter patient data at the point of care. The system runs on PCs and Macintoshes and uses a graphical user interface and object-oriented programming to take advantage of current mouse and pen technologies. The provider acquires all relevant patient data by pointing and clicking at selections on input screens, many of which contain anatomical drawings to help the provider quickly and accurately describe patient findings. The system also generates a grammatically correct progress note using the problem-oriented structure. Furthermore, items identified in the assessment and plans portion of the program can be ported to expert systems for medical decisions assistance or to billing systems. The system allows the provider to obtain the necessary information on a focused patient visit in less than 5 min or to enter a complete history and physical.     

STRUCTURELAB: a heterogeneous bioinformatics system for RNA structure analysis

STRUCTURELAB is a computational system that has been developed to permit the use of a broad array of approaches for the analysis of the structure of RNA. The goal of the development is to provide a large set of tools that can be well integrated with experimental biology to aid in the process of the determination of the underlying structure of RNA sequences. The approach taken views the structure determination problem as one of dealing with a database of many computationally generated structures and provides the capability to analyze this data set from different perspectives. Many algorithms are integrated into one system that also utilizes a heterogeneous computing approach permitting the use of several computer architectures to help solve the posed problems. These different computational platforms make it relatively easy to incorporate currently existing programs as well as newly developed algorithms and to best match these algorithms to the appropriate hardware. The system has been written in Common Lisp running on SUN or SGI Unix workstations, and it utilizes a network of participating machines defined in reconfigurable tables. A window-based interface makes this heterogeneous environment as transparent to the user as possible.     

PROFILER: a tool for automatic searching of internally maintained databases

A new application program, the BIOINFORMATICS PROFILER, is described which simplifies the analysis of new genome sequence information appearing on a daily basis. Control tasks are defined through an intuitive graphical user interface and are executed at user defined nightly intervals. Electronic mail is sent to indicate that search results have been found. All task output is presented to users in the form of hypertext (HTML), allowing easy browsing. Currently supported tasks include BLAST and FastA sequence searching, keyword based searching of network news articles and WAIS databases, examination of GenBank sequence entries using regular expressions and boolean operations and protein sequence motif searching.     

The detrimental effect of increased endometrial thickness on implantation and pregnancy rates and outcome in an in vitro fertilization program

In the framework of the EU BIOTECH PROGRAM and within the 'MITBASE: a comprehensive and integrated database on mtDNA' project, we have prepared a pilot database (MitBASE Pilot) on nuclear genes involved in mitochondrial biogenesis and its regulation in Saccharomyces cerevisiae. MitBASE Pilot includes nuclear genes encoding mitochondrial proteins as well as nuclear genes encoding products which are localised in other sub-cellular compartments but nevertheless interact with mitochondrial functions. Genes have been classified on the basis of the mitochondrial process in which they participate and the mitochondrial phenotype of the gene knockout. The structure of the MitBASE Pilot database has been conceived for a flexible organisation of the information. An intuitive visual query system has been developed which allows users to select information in different combinations, both in the query and the output format, according to their needs. MitBASE Pilot is a relational database, is maintained at the EMBL-European Bioinformatics Institute (EBI) and is available at the World Wide Web site http://www3.ebi.ac. uk/Research/Mitbase/mitbiog.pl     

Effects of variation in system responsiveness on user performance in virtual environments

System responsiveness (SR) is defined as the elapsed time until a system responds to user control. SR fluctuates over time, so it must be described statistically with mean (MSR) and standard deviation (SDSR). In this paper, we examine SR in virtual environments (VEs), outlining its components and methods of experimental measurement and manipulation. Three studies of MSR and SDSR effects on performance of grasp and placement tasks are then presented. The studies used within-subjects designs with 11, 12, and 10 participants, respectively. Results showed that SDSR affected performance only if it was above 82 ms. Placement required more frequent visual feedback and was more sensitive to SR. We infer that VE designers need not tightly control SDSR and may wish to vary SR control based on required visual feedback frequency. These results may be used to improve the human-computer interface in a wide range of interactive graphical applications, including scientific visualization, training, mental health, and entertainment.     

Variation in the delivery of health care: the stakes are high

MOTIVATION: Lacking structures resolved at atomic resolution, the great majority of membrane proteins have typically been depicted in a schematic two-dimensional (2D) topology consisting of putative transmembrane domains predicted from hydropathy plots. As more and more sequences of membrane proteins become available from genome projects, there is a need to automate the process of generating the schematic topology while allowing important information, such as the individual amino acid and the extent to which it is conserved in evolution, to be conveniently inspected. We addressed this need by developing a program called VHMPT. RESULTS: VHMPT (a graphical V iewer and editor for H elical line M embrane P rotein T opologies) can automatically generate a schematic 2D topology for a protein with transmembrane helices. Through an interactive graphical interface, VHMPT allows users to modify the layout of the generated topology, label specific amino acid or amino acid groups, and annotate with arrows and texts. Given a multiple sequence alignment file, VHMPT can also color code a normalized conservation score for each amino acid on the generated topology, allowing ready visual recognition of highly conserved (or variable) topological regions. VHMPT is written in Tcl/Tk and can run on platforms that have installed the Tcl/Tk interpreter. AVAILABILITY: The source code and a user manual for VHMPT are available for download at http://www. ibms.sinica.edu.tw/mjhwang/vhmpt. CONTACT: mjhwang@mail.ibms.sinica.edu.tw     

BioViews: Java-based tools for genomic data visualization

Visualization tools for bioinformatics ideally should provide universal access to the most current data in an interactive and intuitive graphical user interface. Since the introduction of Java, a language designed for distributed programming over the Web, the technology now exists to build a genomic data visualization tool that meets these requirements. Using Java we have developed a prototype genome browser applet (BioViews) that incorporates a three-level graphical view of genomic data: a physical map, an annotated sequence map, and a DNA sequence display. Annotated biological features are displayed on the physical and sequence-based maps, and the different views are interconnected. The applet is linked to several databases and can retrieve features and display hyperlinked textual data on selected features. In addition to browsing genomic data, different types of analyses can be performed interactively and the results of these analyses visualized alongside prior annotations. Our genome browser is built on top of extensible, reusable graphic components specifically designed for bioinformatics. Other groups can (and do) reuse this work in various ways. Genome centers can reuse large parts of the genome browser with minor modifications, bioinformatics groups working on sequence analysis can reuse components to build front ends for analysis programs, and biology laboratories can reuse components to publish results as dynamic Web documents.     

Hidden neural networks

A general framework for hybrids of hidden Markov models (HMMs) and neural networks (NNs) called hidden neural networks (HNNs) is described. The article begins by reviewing standard HMMs and estimation by conditional maximum likelihood, which is used by the HNN. In the HNN, the usual HMM probability parameters are replaced by the outputs of state-specific neural networks. As opposed to many other hybrids, the HNN is normalized globally and therefore has a valid probabilistic interpretation. All parameters in the HNN are estimated simultaneously according to the discriminative conditional maximum likelihood criterion. The HNN can be viewed as an undirected probabilistic independence network (a graphical model), where the neural networks provide a compact representation of the clique functions. An evaluation of the HNN on the task of recognizing broad phoneme classes in the TIMIT database shows clear performance gains compared to standard HMMs tested on the same task.     

Sculpting proteins interactively: continual energy minimization embedded in a graphical modeling system

We describe a new paradigm for modeling proteins in interactive computer graphics systems--continual maintenance of a physically valid representation, combined with direct user control and visualization. This is achieved by a fast algorithm for energy minimization, capable of real-time performance on all atoms of a small protein, plus graphically specified user tugs. The modeling system, called Sculpt, rigidly constrains bond lengths, bond angles, and planar groups (similar to existing interactive modeling programs), while it applies elastic restraints to minimize the potential energy due to torsions, hydrogen bonds, and van der Waals and electrostatic interactions (similar to existing batch minimization programs), and user-specified springs. The graphical interface can show bad and/or favorable contacts, and individual energy terms can be turned on or off to determine their effects and interactions. Sculpt finds a local minimum of the total energy that satisfies all the constraints using an augmented Lagrange-multiplier method; calculation time increases only linearly with the number of atoms because the matrix of constraint gradients is sparse and banded. On a 100-MHz MIPS R4000 processor (Silicon Graphics Indigo), Sculpt achieves 11 updates per second on a 20-residue fragment and 2 updates per second on an 80-residue protein, using all atoms except non-H-bonding hydrogens, and without electrostatic interactions. Applications of Sculpt are described: to reverse the direction of bundle packing in a designed 4-helix bundle protein, to fold up a 2-stranded beta-ribbon into an approximate beta-barrel, and to design the sequence and conformation of a 30-residue peptide that mimics one partner of a protein subunit interaction. Computer models that are both interactive and physically realistic (within the limitations of a given force field) have 2 significant advantages: (1) they make feasible the modeling of very large changes (such as needed for de novo design), and (2) they help the user understand how different energy terms interact to stabilize a given conformation. The Sculpt paradigm combines many of the best features of interactive graphical modeling, energy minimization, and actual physical models, and we propose it as an especially productive way to use current and future increases in computer speed.     

Early expression of interleukin-12, p40 subunit and IFN-gamma inhibits regression of AK-5 tumor

The Magnetic Resonance Imaging technique myocardial tagging allows the tracking and measurement of local parameters of heart wall motion. Tagging provides detailed information about regional cardiac function never before available with non-invasive techniques. The growth of this technique has been limited in part by the availability of post-processing tools. We introduce the TAGged cine AnalySIS Tools package (TAGASIST) for the processing of images from this technique. TAGASIST includes a graphical user interface for image segmentation, kinematic analysis, plotting of regional averages as well as multiple subjects (or patient populations) simultaneously, statistical analysis, and a database of all studies processed.     

Graphical User Interface for Guided Acoustic Waves

This paper presents GUIGUW v0.1, a graphical user interface (GUI) for the computation of stress-guided wave dispersive features. The software exploits semianalytical finite-element (SAFE) formulations for the calculation of wave-propagation characteristics. The interface allows for the selection of geometrical, mechanical, and frequency-related parameters for the computation. Isotropic and anisotropic materials with linear elastic and linear viscoelastic rheological behaviors can be considered, and any waveguide cross section can be modeled. For each existing wave, the dispersive results can be represented in terms of wave number, wavelength, phase velocity, group velocity (for undamped waveguides), energy velocity, and attenuation (for damped waveguides). By simply working with the GUI, original results for guided stress waves can be obtained.     

Development of a Virtual Reality Structural Analysis System

This paper discusses the development of virtual structural analysis program (VSAP). This is a virtual environment (VE) based structural analysis system developed through a collaborative effort between the School of Architecture + Design and the Department of Computer Science at Virginia Polytechnic Institute and State Univ. (Virginia Tech). The VSAP was developed by linking a visualization routine using the simple VE library and a structural analysis software, the PC-SAP4. Details of the design of four user interfaces for the VSAP are presented. These user interfaces are: the immersive pen and tablet interface, the desktop interface, the portable immersive interface, and the cave automatic VE immersive interface. Usability studies for each interface were conducted. Results of these studies indicated that the users of VSAP were highly satisfied with the experience. In addition, all the developed interfaces were found to be successful for their specific application.     

IMGT, the International ImMunoGeneTics database

IMGT, the international ImMunoGeneTics database, is an integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) of all vertebrate species, created by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes three databases: LIGM-DB (for Ig and TcR), MHC/HLA-DB and PRIMER-DB (the last two in development). IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 23 000 Immunoglobulin and T cell Receptor sequences from 78 species. MHC/HLA-DB contains Class I and Class II Human Leucocyte Antigen alignment tables. An IMGT tool, DNAPLOT, developed for Ig, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including nucleotide and protein sequences, oligonucleotide primers, gene maps and other genetic data of Ig, TcR and MHC molecules, and to provide a graphical user friendly data access. IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc.fr:8104