On extending the usefulness of projectors in teaching biology

This paper reports the design of an interactive computer program in microbial genetics. The computer program is divided into three stages, background information, simulation, and data treatment. The results obtained from the simulation allow four genes to be sequenced along the bacterial chromosome. The simulation mimics experimental errors, the production of exconjugants and backmutants. The data can be analysed using options contained in the program. The simulation is of particular educational value because it allows the student to work at his own pace and to develop his ability to analyse data in relation to a complex conceptual model.     

Program for the visualization and interactive study of molecules on a calligraphic display system

Mops is a computer program for the visualization and interactive analysis of crystallographic and molecular structures on a calligraphic PS 300 display system. This system allows the interactive display of bond lengths, bond angles and torsion angles with colour coding of atom types as well as crystalline packing interactions. Mops is also capable of easily drawing a chosen image on the screen using the Ortep program. This facility allows the very fast preparation of slides or illustrations.     

MOLPACK: molecular graphics,for studying the packing of protein molecules in the crystallographic unit cell

A graphics program, MOLPACK, has been developed on the Silicon Graphics IRIS-4D computer system for displaying the packing of proteins in the crystallographic unit cell. In addition to the normal viewing operations of rotation, translation and scaling, the program has the ability to translate molecules along the cell axes while maintaining their crystallographic equivalent positions within the unit cell. This allows the user to observe the packing of protein molecules generated by molecular replacement, to create a new packing model or to locate an unknown molecule. A special feature of the program is that up to four independent molecules can be manipulated in the asymmetric unit.     

Automation of the computer handling of gel reading data produced by the shotgun method of DNA sequencing.

This paper describes a computer method for handling gel reading data produced by the shotgun method of DNA sequencing. The method greatly reduces the time the sequencer needs to spend checking and editing his data and yet it produces a consensus sequence for which the accuracy of determination of every base can be clearly shown. The program can take a batch of new gel readings, screen them against vector sequences removing any that match, and then compare and align all the sequences to produce a final consensus. No information is lost in this process as alignments are achieved by making only insertions and because all the individual gel readings are added to a database from which they can be retrieved and displayed lined up one above the other. This allows the user to check on the alignments achieved by the program and if necessary change them. As each gel reading is added to the database the consensus is automatically updated accordingly and used for the next comparisons. This is a much faster process than comparing each new gel against every individual gel in the database.     

Intercellular Ca2+ signalling: the artery wall

The fact that many cells in the cardiovascular system are coupled via gap junctions enables direct intercellular Ca2+ signalling. Ca2+ ions and/or inositol trisphosphate (IP3) can pass through these aqueous pores. Cell-cell coupling can occur between cells of the same type, or via special junctions between adjacent cells of different types. Homocellular coupling acts to amplify and prolong Ca2+ signals, whereas heterocellular coupling allows complex interactions between the cells, including the modulation of their respective responses. This review will focus on the interactions between cells that form the blood vessel wall, illustrating how cell-cell communication defines important physiological functions.     

Multiple association analysis via simulated annealing (MASSA)

SUMMARY: Genome-wide association studies are now technically feasible and likely to become a fundamental tool in unraveling the ultimate genetic basis of complex traits. However, new statistical and computational methods need to be developed to extract the maximum information in a realistic computing time. Here we propose a new method for multiple association analysis via simulated annealing that allows for epistasis and any number of markers. It consists of finding the model with lowest Bayesian information criterion using simulated annealing. The data are described by means of a mixed model and new alternative models are proposed using a set of rules, e.g. new sites can be added (or deleted), or new epistatic interactions can be included between existing genetic factors. The method is illustrated with simulated and real data. AVAILABILITY: An executable version of the program (MASSA) running under the Linux OS is freely available, together with documentation, at http://www.icrea.es/pag.asp?id=Miguel.Perez.     

Generation of synthetic data and experimental designs in evaluating interactions for association studies

Complex diseases, by definition, involve multiple factors, including gene-gene interactions and gene-environment interactions. Researchers commonly rely on simulated data to evaluate their approaches for detecting high-order interactions in disease gene mapping. A publicly available simulation program to generate samples involving complex genetic and environmental interactions is of great interest to the community. We have developed a software package named gs1.0, which has been widely used since its publication. In this article, we present an upgraded version gs2.0, which not only inherits its capacity to generate realistic genotype data but also provides great functionality and flexibility to simulate various interaction models. In addition to a standalone version, a user-friendly web server (http://cbc.case.edu/gs) has been set up to help users to build complex interaction models. Furthermore, by utilizing three three-locus models as an example, we have shown how realistic model parameters can be chosen in generating simulated data.     

Computer simulation of biological systems

The current status of mathematical models of biological systems is reviewed. Advances in supercomputer hardware allows more complex models to be constructed. The new generation of microcomputers are quite adequate for many computer simulations of biological systems. A theory of modeling is being developed to improve the relationship between the real biological system and the model. Deterministic models, stochastic models and applications of control theory and optimization methods are discussed. Examples given include models of molecular structure, of experimental techniques, and of biochemical reactions. It is recommended that experimental biologists consider the use of microcomputers to model the system under study as a part of their research program.     

Programming for the DNA analysis of FCM data on an IBM microcomputer

The analysis of data generated on a flow cytometer (FCM) is often performed on a computer obtained especially for dedicated use with the flow cytometer. This computer component can be expensive and also presents the FCM user with the added burden of mastering specialized programming language or of accepting the secret analytical processes of protected proprietary program routines. We believe that the evolution of more accurate and efficient FCM analyses that have the power to consider complex signal distributions can be assisted by the availability of analysis programs written in languages common to many users. DNA analysis routines written for a relatively inexpensive microcomputer (IBM PC/XT) in Basic and Pascal are described here. The routines can automatically process multiple FCM data files and can provide high-resolution graphic hardcopy. A foreground/background utilization is also described that allows the computer to be available for other uses in the laboratory.     

NMπ—improved re‐implementation of NM+, a software for estimating gene dispersal and mating patterns

This study introduces the NMπ computer program designed for estimation of plant mating system and seed and pollen dispersal kernels. NMπ is a re‐implementation of the NM+ program and provides new features such as support for multicore processors, explicit treatment of dioecy, the possibility of incorporating uniparentally cytoplasmic markers, the possibility of assessing assortative mating due to phenotypic similarity and inference about offspring genealogies. The probability model of parentage (the neighbourhood model) accounts for missing data and genotyping errors, which can be estimated along with regular parameters of the mating system. The program has virtually no restrictions with respect to a number of individuals, markers or phenotypic characters. A console version of NMπ can be run under a wide variety of operating systems, including Windows, Linux or Mac OS. For Windows users, a graphical user interface is provided to facilitate operating the software. The program, user manual and example data are available on http://www.ukw.edu.pl/pracownicy/plik/igor_chybicki/3694/ .     

Plant Taxonomy Today

A computer program for genetic models which has some useful and labour saving features is described. The program allows students with only a rudimentary knowledge of programming to cope easily with complex genetic models. Some applications of the program are discussed.     

PC-based system for an objective quantification of manual movement disability for clinical and scientific purposes

In clinical management and research of movement disorders exact knowledge about the extent of motor impairment is essential. This paper presents a computer program which allows for an objective measurement of manual movement disability. The program was developed for standard hardware and can easily be used in a variety of clinical and research environments. The program runs on MS-DOS computers and uses a Microsoft computer mouse as the only input device. The temporal resolution is 100 Hz, the spatial resolution 400 dots per inch. The user may choose between standard test sets or he may design sets according to his individual needs from a pool of available protocols which includes tracking tasks, ballistic tasks, complex sequential tasks, and finger tapping. All tasks are implemented in a similar way in order to keep the test environment as consistent as possible for the patient. The patient must usually carry out movements which correspond to the movements of a target symbol on the computer screen. This entails the manipulation of a follower symbol, also visible on the computer screen, via the computer mouse. The program itself and the theoretical background of the protocols are described in the paper. Additionally, preliminary results from pilot experiments are presented.     

Simulations of ion current in realistic models of ion channels: the KcsA potassium channel

Realistic studies of ion current in biologic channels present a major challenge for computer simulation approaches. All-atom molecular dynamics simulations involve serious time limitations that prevent their use in direct evaluation of ion current in channels with significant barriers. The alternative use of Brownian dynamics (BD) simulations can provide the current for simplified macroscopic models. However, the time needed for accurate calculations of electrostatic energies can make BD simulations of ion current expensive. The present work develops an approach that overcomes some of the above challenges and allows one to simulate ion currents in models of biologic channels. Our method provides a fast and reliable estimate of the energetics of the system by combining semimacroscopic calculations of the self-energy of each ion and an implicit treatment of the interactions between the ions, as well as the interactions between the ions and the protein-ionizable groups. This treatment involves the use of the semimacroscopic version of the protein dipole Langevin dipole (PDLD/S) model in its linear response approximation (LRA) implementation, which reduces the uncertainties about the value of the protein "dielectric constant." The resulting free energy surface is used to generate the forces for on-the-fly BD simulations of the corresponding ion currents. Our model is examined in a preliminary simulation of the ion current in the KcsA potassium channel. The complete free energy profile for a single ion transport reflects reasonable energetics and captures the effect of the protein-ionized groups. This calculated profile indicates that we are dealing with the channel in its closed state. Reducing the barrier at the gate region allows us to simulate the ion current in a reasonable computational time. Several limiting cases are examined, including those that reproduce the observed current, and the nature of the productive trajectories is considered. The ability to simulate the current in realistic models of ion channels should provide a powerful tool for studies of the biologic function of such systems, including the analysis of the effect of mutations, pH, and electric potentials.     

New direct dynamic models of protein interactions coupled to photosynthetic electron transport reactions

This review covers the methods of computer simulation of protein interactions taking part in photosynthetic electron transport reactions. A direct multiparticle simulation method that simulates reactions describing interactions of ensembles of molecules in the heterogeneous interior of a cell is developed. In the models, protein molecules move according to the laws of Brownian dynamics, mutually orient themselves in the electrical field, and form complexes in the 3D scene. The method allows us to visualize the processes of molecule interactions and to calculate the rate constants for protein complex formation reactions in the solution and in the photosynthetic membrane. Three-dimensional multiparticle computer models for simulating the complex formation kinetics for plastocyanin with photosystem I and cytochrome bf complex, and ferredoxin with photosystem I and ferredoxin:NADP⁺-reductase are considered. Effects of ionic strength are featured for wild type and mutant proteins. The computer multiparticle models describe nonmonotonic dependences of complex formation rates on the ionic strength as the result of long-range electrostatic interactions.     

Application of the recommendation architecture to telecommunications network management.

The recommendation architecture has been proposed as a system architecture which can enable a system to learn to perform a complex combination of interrelated functions. The capability of a system with the recommendation architecture to learn to manage complex telecommunication backbone networks has been investigated. A network model with a number of nodes and links and carrying realistic but randomly generated traffic was used as the target for the management system. Traffic data taken from the model was used as input to the recommendation architecture system. The traffic data was organized into inputs once every 5 minutes, and the management system organized these inputs into a hierarchy of repetition similarity. It was demonstrated that the outputs of this hierarchy provided information on the condition of the network. This output information was a compressed version of the inputs which correlated with major network conditions.     

A program for reading DNA sequence gels using a small computer equipped with a graphics tablet.

A program has been written in BASIC that allows DNA sequence gels to be read by a Tektronix model 4052 computer equipped with a graphics tablet. Sequences from each gel are stored on tape for later transfer to a larger computer where they are melded into a complete overall sequence. The program should be adaptable to other small computers.     

The impact of symbolism on immunogenetics: an application to HLA

The genes coding for the class I human lymphocyte antigens (HLA) are located on chromosome 6. These antigens are involved with the immunological interaction between cells. In some immunogenetic systems, such as HLA in humans, genes are defined by antibody/antigen reaction and are denoted by single symbolic identifiers. This symbolization assumes a one-to-one correspondence between antibodies, antigens and genes. Recent molecular studies, however, suggest that HLA antibody/antigen reaction is complex and most HLA class I specific antibodies may not uniquely identify a single allelic product. Where cross-reactivity is present in an immunogenetic system it is important to label each reagent with symbols corresponding to all genes coding for antigens with which the reagent will react. The problems of cross-reactive groups and unexplained linkage relations may be elucidated by the redefinition and clarification of certain HLA antigens. A computer program can suggest such labelling schemes using input given by phenotype reaction patterns with a panel of reagents. When this program was applied to data on the class I HLA antigens a genetic model was suggested that differs somewhat from the currently accepted model. The new model is able to predict what would appear as linkage relations in the accepted model. Our methodology can provide alternate models to guide in typing cloned genes in terms of the HLA locus and alleles.     

Transient state kinetics tutorial using the kinetics simulation program, KINSIM.

This article provides an introduction to a computer tutorial on transient state kinetics. The tutorial uses our Macintosh version of the computer program, KINSIM, that calculates the time course of reactions. KINSIM is also available for other popular computers. This program allows even those investigators not mathematically inclined to evaluate the rate constants for the transitions between the intermediates in any reaction mechanism. These rate constants are one of the insights that are essential for understanding how biochemical processes work at the molecular level. The approach is applicable not only to enzyme reactions but also to any other type of process of interest to biophysicists, cell biologists, and molecular biologists in which concentrations change with time. In principle, the same methods could be used to characterize time-dependent, large-scale processes in ecology and evolution. Completion of the tutorial takes students 6-10 h. This investment is rewarded by a deep understanding of the principles of chemical kinetics and familiarity with the tools of kinetics simulation as an approach to solve everyday problems in the laboratory.     

Armadillo 1.1: an original workflow platform for designing and conducting phylogenetic analysis and simulations

In this paper we introduce Armadillo v1.1, a novel workflow platform dedicated to designing and conducting phylogenetic studies, including comprehensive simulations. A number of important phylogenetic and general bioinformatics tools have been included in the first software release. As Armadillo is an open-source project, it allows scientists to develop their own modules as well as to integrate existing computer applications. Using our workflow platform, different complex phylogenetic tasks can be modeled and presented in a single workflow without any prior knowledge of programming techniques. The first version of Armadillo was successfully used by professors of bioinformatics at Université du Quebec à Montreal during graduate computational biology courses taught in 2010-11. The program and its source code are freely available at: .