An interactive toxicological data handling system for a PDP-12 computer.

This paper describes a program developed for the cataloguing, storage and retrieval of toxicological data. The user can, through dialogue with the program, enter and update data, and request reports with statistical analyses. The system is written in the FOCAL-12 language for a PDP-12 laboratory computer, and is suitable for a larger number of moderately-sized experiments.     

A comprehensive package for DNA sequence analysis in FORTRAN IV for the PDP-11.

A computer package written in Fortran-IV for the PDP-11 minicomputer is described. The package's novel features are: software for voice-entry of sequence data; a less memory intensive algorithm for optimal sequence alignment; and programs that fit statistical models to nucleic acid and protein sequences.     

Multidimensional curve fitting program for biological data

A program written for use with the IBM-PC can be used to find least squares solutions to linearized multidimensional equations. The program is 'user-friendly' by requiring little from the user except to make decisions; most responses can be entered by a single keystroke. Once data are entered by the user, they can be repeatedly manipulated, graphed, and correlated. Many models relating data variables can be tried relatively easily, and best fit results found. Examples using respiratory mechanical data illustrate the ease of model comparisons.     

An automated laboratory control system: collection and analysis of behavioral and electro-physiological data.

A system of man-machine interactive PDP-11 assembly language programs is described which presents stimuli to a subject and records and analyzes behavioral and evoked potential data. The system was designed for researchers with no knowledge of computer programming and enables the user to create complicated sequences of stimulus presentations ("trials") and sequences of successive trials ("runs"), with no new programming required. The system is written for DEC.s DECLAB 11/40 system.     

Probability of quantal transmitter release from nerve terminals: theoretical considerations in the determination of spatial variation

The release of transmitter occurs in discrete quantal units, such that the number released (m) is equal to the number available (n) times the average probability of release (p). Although a common method of estimating these parameters is to use simple binomial statistics, results may be biased if there is spatial or temporal variation in n and p (vars p, vart n, vart p). The problem arises in the simultaneous analysis of five variables, which is impractical due to the complexity and margin of error involved. The proposed solution is to eliminate two variables (vart n, vart p) by assuming stationarity and to obtain the required information from the first three moments of m. The resulting quadratic equation gives two solutions, p1 and p2. Computer simulation of quantal output as a function of vars p indicates that p1 is the better estimator of p when vars p is small, but that p2 is better when vars p is large. This changeover or "inflection" occurs at points which correspond to the maximum vars p obtainable by unimodal distributions of p (larger vars p being obtained by bimodal distributions). Comparison of the simulated histogram of m with those predicted by p1 and p2 shows that p1 provides the better fit, whether vars p is large or small. This discrepancy indicates that histogram analysis is unable to distinguish the appropriate estimate. The major limitations in the procedure can be met by assuming (1) stationarity (which can be attained and tested experimentally), and (2) normal distribution of p (since vars p is then less than "inflection" point, p1 will always be the correct estimate). The overall findings demonstrate that vars p and unbiased estimates of n and p may be calculated, provided reasonable assumptions are made. This in turn should allow the continued use of quantal parameters for describing transmitter release.     

Elusive locus of control in biological development: genetic versus developmental programs.

Taken as a composite, the meaning of the composite term "genetic program"-widely taken to suggest an explanation of biological development - simultaneously depends upon and underwrites the particular presumption that a "plan of procedure" for development is itself written in the sequence of nucleotide bases. Is this presumption correct? I want to argue that, at best, it must be said to be misleading, and at worst, simply false: To the extent that we may speak at all of a developmental program, or of a set of instructions for development, in contra-distinction to the data or resources for such a program, current research obliges us to acknowledge that these "instructions" are not written into the DNA itself (or at least, are not all written in the DNA), but rather are distributed throughout the fertilized egg. I will argue that the notion of genetic program depends upon, and sustains, a fundamental category error in which two independent distinctions, one between "genetic" and "epigenetic," and the other, between program and data, are pulled into mistaken alignment. The net effect of such alignment is to reinforce two outmoded associations: on the one hand, between "genetic" and active, and, on the other, between "epigenetic" and passive. J. Exp. Zool. (Mol. Dev. Evol.) 285:283-290, 1999.     

Using least median of squares for structural superposition of flexible proteins

Background

The conventional superposition methods use an ordinary least squares (LS) fit for structural comparison of two different conformations of the same protein. The main problem of the LS fit that it is sensitive to outliers, i.e. large displacements of the original structures superimposed.

Results

To overcome this problem, we present a new algorithm to overlap two protein conformations by their atomic coordinates using a robust statistics technique: least median of squares (LMS). In order to effectively approximate the LMS optimization, the forward search technique is utilized. Our algorithm can automatically detect and superimpose the rigid core regions of two conformations with small or large displacements. In contrast, most existing superposition techniques strongly depend on the initial LS estimating for the entire atom sets of proteins. They may fail on structural superposition of two conformations with large displacements. The presented LMS fit can be considered as an alternative and complementary tool for structural superposition.

Conclusion

The proposed algorithm is robust and does not require any prior knowledge of the flexible regions. Furthermore, we show that the LMS fit can be extended to multiple level superposition between two conformations with several rigid domains. Our fit tool has produced successful superpositions when applied to proteins for which two conformations are known. The binary executable program for Windows platform, tested examples, and database are available from https://engineering.purdue.edu/PRECISE/LMSfit.     

A set of programs for analysis of kinetic and equilibrium data

A program package that can be used for analysis of a wide rangeof kinetic and equilibrium data is described. The four programswere written in Turbo Pascal and run on PC, XT, AT and compatibles.The first of the programs allows the user to fit data with 16predefined and one user-defined function, using two differentnon-linear least-squares procedures. Two additional programsare used to test both the evaluation of model functions andthe least-squares fits. One of these programs uses two simpleprocedures to generate a Gaussian-distributed random variablethat is used to simulate the experimental error of measurements.The last program simulates kinetics described by differentialequations that cannot be solved analytically, using numericalintegration. This program helps the user to judge the validityof steady-state assumptions or treatment of kinetic measurementsas relaxations. Received on September 19, 1989; accepted on March 16, 1990     

A free derivate program for non-linear regression analysis of enzyme kinetics to be used on small computers

A non-linear regression program, written in BASIC, is describe. The program uses the Marquardt's algorithm as modified by Reich et al. (Eur. J. Biochem., 26 (1972) pp.368–379). The user only supplies the expression to fit, since the program uses numerical differentiation. It is possible to fit models of 1 substrate, 2 substrates, 1 substrates and 1 inhibitor, and 2 substrates and 1 inhibitor. Likewise, several weighting patterns, as well as a simple or robust regression, can be selected.     

A microcomputer method for designing optimal experiments for estimating enzyme kinetic parameters

A computer program, written in BASIC, for designing optimal experiments with the aim of evaluating estimates of the parameters for any enzyme kinetic model is given. This computer program can be run on any microcomputer with less than 32 Kbytes of random access memory. The program uses the termed D-optimization design criterion, which minimizes the determinant of the variance-covariance matrix. The user only supplies the rate equation, the maximum and minimum concentrations of substrates and inhibitors, the weighting pattern, and the best possible values of the parameters. The computer supplies the optimal substrate and inhibitor concentrations (one for each parameters), for estimating the parameter values, and the determinant of the variance-covariance matrix. Likewise, the microcomputer supplies the eigenvalues and eigenvectors of information and redundancy matrices, the sensitivity and the global redundancy.     

Conversion of linear histogram flow cytometry data to a logarithmic display

A routine is described that readily allows the rescaling of linear histographic data to a corresponding logarithmic histogram. This procedure significantly improves data display, particularly where a wide range in the measured parameter is encountered. The logarithmic scale displays peaks with band widths more proportional to their respective coefficients of variation than is the case in a linear display. Rescaling several linear histograms to a common logarithmic scale allows the combination of these linear data even though the linear ranges are different. This routine is presented as a program written in BASIC for execution on a microcomputer.     

Operant conditioning and behavioral analyses using a minicomputer.

An operant conditioning and data analysis software system was developed for use on a PDP-12A minicomputer. The operant software functions in quasi time-sharing fashion to control and acquire data from any peripheral device that operates in the binary mode. In addition to independently running different experiments in near simultaneous fashion, the program also provides information on the current status of each experiment using a cathode ray-tube display. Response data from each experimental subject is stored on magnetic tape and analyzed, off-line, by the data analysis portion of the software system. A discussion of the operation of this system is given for one possible application: visual discrimination training.     

Design and analysis of accelerated degradation tests for the stability of biological standards II. A flexible computer program for data analysis

The accelerated degradation test is commonly used to predict the stability of a biological standard during long-term storage at low temperature. A flexible computer program is described which has been written to analyse degradation test results by the method of maximum likelihood. In addition to predicting the degradation rate at low temperature, the program furnishes estimates of statistical precision and it carried out a test of goodness of fit of the data to the assumed Arrhenius equation model.     

A program which automatically quantitates gel electrophoretic autoradiograms

The use of a computer-coupled film scanner to measure and analyze autoradiograms of gel electropherograms is described. A program has been written which fits Gaussian curves to the complex band pattern that constitutes a density profile without the need for estimated parameters in the input. The great majority of the fits are satisfactory. This program, which is written in FORTRAN, runs on a small, inexpensive computer. Another program which approximates a Gaussian least squares fit has been run for comparison; this procedure can also be used to refine occasional unsatisfactory fits. Finally, a program has been written which sums the density profile within specified limits, so that the integrated intensities of bands due to isolated protein components may be found.     

A computer program suitable for fitting linear models when the dependent variable is dichotomous, polichotomous or censored survival and non-linear models when the dependent variable is quantitative.

Given a set of measurements of s explanatory variables corresponding to each experimental unit, a computer program, whose methodological background can be found in [2] has been written in FORTRAN IV language in order to perform regression analyses when the dependent variable is: (i) dichotomous; (ii) polichotomous; (iii) censored survival. In the two former the Cox's [6] linear logistic models are used while in the third one it has been resorted to the models suggested by Feigl and Zelen [8]. The statistical estimation procedure is maximum likelihood and among the different algorithms developed to reach this goal, the one published by Van der Voort and Dorpema [3], has been utilized. Furthermore, when the dependent variable is quantitative, the program is suitable to fit any function non-linear in the parameters; the pertinent function and its first and second derivatives must be provided by the user. In the present version, implemented on a Univac 1106 machine, the program fits directly the Gompertz function.     

DRAWNA: A program for drawing schematic views of nucleic acids

A program for drawing automatically exact and schematic views of nucleic acids is described. The program is written in C ANSI and uses the Silicon Graphics GL and Xirisw libraries within the X1 1/Motif environment. Through menus, the user can choose, specify, and manipulate in real time the three-dimensional views to be displayed. Drawing options include partitioning of structures into differently colored or shaped fragments, representation of backbones as flat or with conic-section ribbons, display of paired or free bases as rods, and display of surfaces as filled or outlined and stereo or depth-cued views.     

A program for maximum likelihood estimation and likelihood ratio tests in one-locus ABO-like systems based upon population phenotype data.

Phenotypes in an ABO-like system of a number of genetically-independent persons from a number of populations are supposed to be observed. The program which is written in FORTRAN calculates maximum likelihood estimates of gene frequencies and their standard errors in each population and in the populations taken together. Furthermore the program calculates expected values and likelihood ratio and goodness of fit chi-square tests of Hardy-Weinberg equilibrium. If several subpopulations are pooled together a likelihood ratio test of homogeneity is performed.