Frequencies of paired open-closed durations of ion channels. Method of evaluation from single-channel recordings.

The probability of the occurrence of consecutive closed-open or open-closed intervals of specified durations in single-channel recordings may be of enormous help in the establishment of the kinetic scheme that describes the behavior of the channel. The relevant probability functions are linear combinations of products of exponential functions of the closed durations and the open durations. A method is presented for the evaluation of the coefficients of the exponential functions using a set of auxiliary functions that are each orthogonal to all but one of the exponential functions. The coefficients in the probability functions may then be obtained from the experimental data by multiplication by the auxiliary functions and subsequent simple integration operations. Furthermore, the variance to be expected in the evaluated numerical magnitude of the parameters, due to the stochastic nature of the transitions in the channel conductance, is also readily estimated by use of the above auxiliary functions. The procedure is illustrated by analysis of synthetic data obtained from computer simulated experiments.     

C/C++ Coding for Matrix Pseudo Inverses in Clinical Near Infrared Spectroscopy

Near infrared spectroscopy is used clinically to investigate patterns of change in cerebral oxygenation. We have shown that differences reported between authors are likely the result of computer encoding errors in the manipulation of matrices. Current methods compute the inverse of a non-square matrix to derive chromophore concentration values, and solution of another non-square matrix to derive polynomial coefficients of a least squares best fit curve from which the first derivative can be used to estimate blood flow values. Encoding of these pseudo inverses involves too many nested looping steps to easily identify encoding errors. We have given C/C++ source code along with sample numerical values at the termination of each loop within the algorithm. This provides counter checking for future software development by other programmers, and also permits other investigators to report whether the software used for their experiments agrees with previously published material.     

C/C++ Coding for Matrix Pseudo Inverses in Clinical Near Infrared Spectroscopy

Near infrared spectroscopy is used clinically to investigate patterns of change in cerebral oxygenation. We have shown that differences reported between authors are likely the result of computer encoding errors in the manipulation of matrices. Current methods compute the inverse of a non-square matrix to derive chromophore concentration values, and solution of another non-square matrix to derive polynomial coefficients of a least squares best fit curve from which the first derivative can be used to estimate blood flow values. Encoding of these pseudo inverses involves too many nested looping steps to easily identify encoding errors. We have given C/C++ source code along with sample numerical values at the termination of each loop within the algorithm. This provides counter checking for future software development by other programmers, and also permits other investigators to report whether the software used for their experiments agrees with previously published material.     

A nomogram for deconvolution of single exponential fluorescence decays.

An extremely rapid technique for deconvolving single exponential luminescence decay data is described that involves essentially no mathematical manipulation of the experimental data. The method permits "real time" measurement of deconvolved luminescence lifetimes with conventional pulsed, lifetime-fluorometers and phosphorimeters. The method assumes that the true luminescence decay of the chromophore is accurately represented by a single exponential decay function.     

A computer program for Wiener filtering of evoked potential data.

We have developed a computer program for Wiener filtering of evoked potential data. The basic algorithm involves computation of the difference berween the power spectrum of the sweep sum and the sum of power spectra of individual sweeps. Power spectra are computed by means of the discrete Fourier transform. The program is now being run on a LSI-11 computer in a neurophysiology research laboratory to analyze somatic evoked potential data from monkeys.     

ChemChains: a platform for simulation and analysis of biochemical networks aimed to laboratory scientists

Background  

New mathematical models of complex biological structures and computer simulation software allow modelers to simulate and analyze biochemical systems in silico and form mathematical predictions. Due to this potential predictive ability, the use of these models and software has the possibility to compliment laboratory investigations and help refine, or even develop, new hypotheses. However, the existing mathematical modeling techniques and simulation tools are often difficult to use by laboratory biologists without training in high-level mathematics, limiting their use to trained modelers.     

Background and peak evaluation of one parameter flow karyotypes on a PC/AT computer

Flow cytometry has become a fast, quantitative method for the classification of metaphase chromosomes in suspension (flow karyotyping) stained with fluorescent dyes. Such a flow karyotype (frequency distribution of the fluorescence signals) consists of several peaks. The peak pattern characterizes the analyzed chromosome complement. In many cases flow karyotypes contain a continuum of an unspecific background deriving from chromosome fragments or chromosome aggregates. For the quantitative evaluation of a flow karyotype this background has to be subtracted by a suitable background function. In this approach the application of chi 2-functions is described. The feasibility of this method to flow karyotypes has been concluded from a computer simulation of chromosome breaking under different conditions. In spite of the rather rough assumptions of the model compared to the complex reasons that influence chromosome breaking, the chi 2-function fits the background better than the exponential function in current use. The approximation of a Gaussian distribution function by the chi 2-function also makes it possible to use the same subtraction procedure for chromosome aggregates. The procedure was tested for isolated chromosomes of Chinese hamster cell lines under different states of breaking. For further evaluation of one parameter flow karyotypes a setup of computer routines has been developed for PC/AT and compatible computer systems. Different peak values of these flow karyotypes can be determined (e.g. peak mean, standard deviation, absolute and relative peak area etc.). The applied method is to fit Gaussian curves to each peak of an experimentally measured histogram by using an interactive program. Fluctuations depending on 'noise' may be suppressed by a 'k-nearest-neighbours' smoothing procedure.     

Improvement in radiographic contrast media through the development of colloidal or particulate media: an analysis.

In the field of active and passive transport of substances across epithelial membranes little progress has been made, mostly for technical reasons, towards a comprehensive view of a wealth of isolated laboratory data. The present study is an attempt to advance the use of the method of computer simulation, with application of the “Continuous System Modelling Program” into the field of membrane transport. High speed of operation and great versatility make this procedure uniquely suitable to transport studies on multicompartment biological systems, such as epithelia. Basic prerequisites are, a detailed knowledge of the morphological parameters of the system, and an abundance of often isolated laboratory data against which the function of a model membrane can be checked. The simulation process becomes then a study of finding the constraints on all rate constants involved (a few of which may be known) which lead to results compatible with experimental facts. Whereas computer modelling is no substitute for experimental studies, it is one way of arriving at a comprehensive view of the complex flow patterns in such complex structures as epithelia. The computer simulation technique can lead to new, testable predictions, and it gives the laboratory investigator a critical perspective of potential pitfalls in experimental techniques used in studies on fluxes in structures as small as those encountered in epithelia. The usefulness of computer simulation in the field of membrane transport is exemplified by applying it to the problem of the initial rate of uptake of Na⁺ by frog skin epidermis. It is shown, here, that the computer data are in excellent agreement with experimental data on epidermis. Beyond this, the computer data permit calculations on kinetic parameters, e.g. Na⁺ pool sizes and rates of Na⁺ fluxes between compartments, which, for the present at least, cannot be directly measured.     

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.     

Field estimates of feeding rate for Gammarus pseudolimnaeus (Crustacea: Amphipoda) in the Credit River, Ontario

SUMMARY. The feeding rate of G. pseudolimnaeus was measured monthly for 7 months in the field by monitoring the decline in weight of gut contents when the amphipod was starved. This decline was modelled by an exponential regression of weight on time. As the amphipods appeared to be continuous feeders, feeding rate was calculated by multiplying the dry weight of a full gut by the specific rate of emptying, i.e., the slope of the exponential regression. Specific rate of emptying was independent of animal size, but increased with temperature. Therefore, food has a longer period in which to be digested at low temperatures, which suggests that assimilation efficiency may increase.
However, the assimilation efficiency of amphipods feeding on decaying maple leaves in the laboratory was only 10% and did not vary with temperature. Ingestion and egestion rates were measured in the laboratory by weighing amounts eaten and defecated. The turnover time of the contents of a full gut in the laboratory often agreed very well with turnover time measured in the field, i.e., the reciprocal of the specific rate of emptying, thus confirming the use of an exponential regression.     

SOLPRO: theory and computer program for the prediction of SOLution PROperties of rigid macromolecules and bioparticles

Single-valued hydrodynamic coefficients of a rigid particle can be calculated from existing theories and computer programs for either bead models or ellipsoids. Starting from these coefficients, we review the procedures for the calculation of complex solution properties depending on rotational diffusion, such as the decays of electric birefringence and fluorescence anisotropy. We also describe the calculation of the scattering form factor of bead models. The hydrodynamic coefficients and solution properties can be combined to give universal, shape-dependent functions, which were initially intended for ellipsoidal particles, and are extended here for the most general case. We have implemented all these developments in a new computer program, SOLPRO, for calculation of SOLution PROperties, which can be linked to existing software for bead models or ellipsoids. Accepted: 1 November 1996     

A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development

Disrupted-In-Schizophrenia-1 (DISC1), originally identified at the breakpoint of a chromosomal translocation that is linked to a rare familial schizophrenia, has been genetically implicated in schizophrenia in other populations. Schizophrenia involves subtle cytoarchitectural abnormalities that arise during neurodevelopment, but the underlying molecular mechanisms are unclear. Here, we demonstrate that DISC1 is a component of the microtubule-associated dynein motor complex and is essential for maintaining the complex at the centrosome, hence contributing to normal microtubular dynamics. Carboxy-terminal-truncated mutant DISC1 (mutDISC1), which results from a chromosomal translocation, functions in a dominant-negative manner by redistributing wild-type DISC1 through self-association and by dissociating the DISC1-dynein complex from the centrosome. Consequently, either depletion of endogenous DISC1 or expression of mutDISC1 impairs neurite outgrowth in vitro and proper development of the cerebral cortex in vivo. These results indicate that DISC1 is involved in cerebral cortex development, and suggest that loss of DISC1 function may underlie neurodevelopmental dysfunction in schizophrenia.     

Brain-controlled interfaces: movement restoration with neural prosthetics

Brain-controlled interfaces are devices that capture brain transmissions involved in a subject's intention to act, with the potential to restore communication and movement to those who are immobilized. Current devices record electrical activity from the scalp, on the surface of the brain, and within the cerebral cortex. These signals are being translated to command signals driving prosthetic limbs and computer displays. Somatosensory feedback is being added to this control as generated behaviors become more complex. New technology to engineer the tissue-electrode interface, electrode design, and extraction algorithms to transform the recorded signal to movement will help translate exciting laboratory demonstrations to patient practice in the near future.     

Exponential function of chymotrypsin action

Enzyme kinetics are usually described by the hyperbolic Michaelis-Menten equation, but they can also be described by the following exponential function: -dS/dt = Vm [1 - exp (-S/Km)]. The time-dependent decrease of the substrate (-dS/dt) is an exponential function of maximal velocity (Vm), the Michaelis constant (Km) and the actual substrate value (S). This exponential function is based on the assumption that the association of the substrate-enzyme complex is a concentration-dependent process, whereas the transformation of the substrate-enzyme complex is time-dependent. It can be shown that this exponential function is a more general solution of which the hyperbolic Michaelis-Menten equation is a special derivative under the conditions of low substrate (S) and high constant (Km) values. If the association process is time-dependent, the decline in substrate values will show a more concave curve. However, exponential functions in general are more concave than hyperbolic functions. Probably, therefore, the enzyme action of chymotrypsin could be described more appropriately by the present exponential function than by the conventional hyperbolic function.     

Multiplex,megaplex, index,and complex: the present and future of laboratory diagnostics in rheumatology

In a recent issue of Arthritis Research & Therapy, Chandra and colleagues described the use of multiple multiplex immunoassays and complex computer algorithms to investigate the possibility of improved laboratory diagnosis and novel classification of rheumatoid arthritis on the basis of biomarkers. Such complex predictive tools in rheumatology can be guided by the experience of multiplex testing in oncology, which has demonstrated the importance of uniform specimen handling and prospectively collected specimen repositories. Although there are high expectations for these complex approaches, they require careful evaluation.     

Mechanical Method of Inoculating Plates for Antibiotic Sensitivity Testing

A mechanical method of inoculating culture plates for antibiotic sensitivity testing is described. This method, which involves the use of a modified laboratory centrifuge, is rapid and provides a homogeneous distribution of organisms.     

Some interrelationships among the regression coefficient estimates arising in a class of models appropriate to response-time data.

Interrelationships among three response-time models which incorporate covariate information are explored. The most general of these models is the logistic-exponential in which the log odds of the probability of responding in a fixed interval is assumed to be a linear function of the covariates; this model includes a parameter W for the width of discrete time intervals in which responses occur. As W leads to O this model is equivalent to a continuous time exponential model in which the log hazard is linear in the covariates. As W leads to infininity it is equivalent to a continuous time exponential model in which the hazard itself is a linear function of the covariates. This second model was fitted to the data used in an earlier publication describing the logistic exponential model, and very close agreement of the estimates of the regression coefficients is demonstrated.