Treatment of radioimmunoassay data: A computer program for curve-fitting and dose interpolation using orthogonal polynomials

We propose a method allowing the automatic exploitation of radioimmunoassay results. The standard curve is calculated according to two models; a linear model by Logit-Log transformation of data and another one using Fisher's orthogonal polynomials. The computer programs are written in FORTRAN IV.     

A program for fitting of hypnograms and other biological data by orthogonal polynomials.

Many biological phenomenon are nonlinear and poorly approximated by linear regression. The program POLFIT calculates curvilinear regressions by fitting of orthogonal polynomials. This program, as well as two supporting programs (CORREC: disk storage, and CALCML: calculation of cumulated values of series of observations), was primarily designed for the study of the temporal organization of sleep components. They can be used as well for any other kind of biological data.     

A cross-platform public domain PC image-analysis program for the comet assay

The single-cell gel electrophoresis, also known as the comet assay, has gained wide-spread popularity as a simple and reliable method to measure genotoxic and cytotoxic effects of physical and chemical agents as well as kinetics of DNA repair. Cells are generally stained with fluorescent dyes. The analysis of comets--damaged cells which form a typical comet-shaped pattern--is greatly facilitated by the use of a computer image-analysis program. Although several image-analysis programs are available commercially, they are expensive and their source codes are not provided. For Macintosh computers a cost-free public domain macro is available on the Internet. No ready for use, cost-free program exists for the PC platform. We have, therefore, developed such a public domain program under the GNU license for PC computers. The program is called CASP and can be run on a variety of hardware and software platforms. Its practical merit was tested on human lymphocytes exposed to gamma-rays and found to yield reproducible results. The binaries for Windows 95 and Linux, together with the source code can be obtained from: http://www.casp.of.pl.     

A personal computer program for large-scale comparisons of related nucleotide sequences

A personal computer program (COMPSEQ) has been developed whichcan present an informative listing of pre-aligned exonic nucleotidesequences and of their translations to amino acid sequencesas well run triplet-oriented analyses on these sequences ina given reading frame. The sequence listing focuses on the differencesbetween related sequences by suppressing the concordances betweenthem.     

A technique for joint center analysis using a stored program calculator

For a long time in the study of joint kinematics, the instant center of rotation in plane motion was obtained through graphic drawings. Since then the study of joint kinematics has become three-dimensional involving the use of computers. For this paper a stored-program calculator has been used as it is a precise instrument and several films can be used even if their positions are very close to one another.

A movement is never perfectly plane, it was important to define a coefficient (in percentage) to qualify the more or less plane character of a movement.

We believe that an analytical location is a better way than using graphic drawings of I.C.R.:

1. (1) to smooth the raw coordinates;

2. (2) to calculate the plane motion coefficient in order to eliminate an X-Ray picture of a whole series of pictures for lack of plane character;

3. (3) to define in the results an error rectangle whose dimensions are linked to errors in the observation and then to pick out among the points of a body those with the smallest risk for error.

To probe this method the two radio-ulnaris joints have been studied. At present studies are being carried on to compare the I.C.R.'s behaviour of the lumbar spine during a motion of lateral inflexion both in the case of normal people and people with scoliosis.     

A robust orthogonal algorithm for system identification and time-series analysis

We describe and illustrate methods for obtaining a parsimonious sinusoidal series representation or model of biological time-series data. The methods are also used to identify nonlinear systems with unknown structure. A key aspect is a rapid search for significant terms to include in the model for the system or the time-series. For example, the methods use fast and robust orthogonal searches for significant frequencies in the time-series, and differ from conventional Fourier series analysis in several important respects. In particular, the frequencies in our resulting sinusoidal series need not be commensurate, nor integral multiples of the fundamental frequency corresponding to the record length. Freed of these restrictions, the methods produce a more economical sinusoidal series representation (than a Fourier series), finding the most significant frequencies first, and automatically determine model order. The methods are also capable of higher resolution than a conventional Fourier series analysis. In addition, the methods can cope with unequally-spaced or missing data, and are applicable to time-series corrupted by noise. Fially, we compare one of our methods with a wellknown technique for resolving sinusoidal signals in noise using published data for the test time-series.     

Pharmacokinetic analysis and calculations using a program for the minicalculator TI-59

The described pharmacokinetic program for TI-59 is in clinical practice applicable in analyses of plasma concentration profiles established after single-dose, intravenous or oral administration of drugs showing one- or two-compartment first-order pharmacokinetics. Analysis of multiple dose, steady state plasma concentration data may also be carried out. Predictions of mean steady state plasma concentrations related to multiple dose drug administration are obtainable on the basis of a preceding single-dose pharmacokinetic analysis. The program contains routines for: exponential regression analysis, determination of and treatment of residuals, simulation of plasma concentration curves, corrections for time-defined intravenous infusion substituting for bolus injection, determination of and correction for lag-time and routines for calculation of fitted and derived pharmacokinetic parameters. Naproxen and theophylline plasma concentration data were used to demonstrate the practical applications of the program.     

A methodology for performing global uncertainty and sensitivity analysis in systems biology

Accuracy of results from mathematical and computer models of biological systems is often complicated by the presence of uncertainties in experimental data that are used to estimate parameter values. Current mathematical modeling approaches typically use either single-parameter or local sensitivity analyses. However, these methods do not accurately assess uncertainty and sensitivity in the system as, by default, they hold all other parameters fixed at baseline values. Using techniques described within we demonstrate how a multi-dimensional parameter space can be studied globally so all uncertainties can be identified. Further, uncertainty and sensitivity analysis techniques can help to identify and ultimately control uncertainties. In this work we develop methods for applying existing analytical tools to perform analyses on a variety of mathematical and computer models. We compare two specific types of global sensitivity analysis indexes that have proven to be among the most robust and efficient. Through familiar and new examples of mathematical and computer models, we provide a complete methodology for performing these analyses, in both deterministic and stochastic settings, and propose novel techniques to handle problems encountered during these types of analyses.     

A computer program for the analysis of dental arch form using the cubic spline function.

This paper presents the details and logic of a FORTRAN computer program which fits a cubic interpolatory spline to a set of data points digitized from an exact size photographic reproduction of a dental model. It also measures the length of the arc and computes a set of normals to the curve to be used in evaluating the error in the fit of the spline. The program is used in studies of dental arch form and is useful in evaluating changes in the form of the arches due to orthodontic treatment. The measurement of the arc length provides an adequate assessment of space available in the dental arch, which is of importance to the orthodontist.     

Spectrum analysis of the r-r interval using a PC]

Spectral analysis of r-r variability has been recently proposed as a clinical tool to assess the autonomic nervous system function. In this article we present the results obtained using an equipment and an analysis software (based on Maximum Entropy Method) developed in our laboratory. Analyzing the tachograms derived from prolonged ECG registrations of 12 young healthy subjects, 24 to 36 years old (mean 31 +/- 4), we observed the two classic components of the signal: a low frequency component (0.7 +/- 0.2 Hz) and a high frequency component (0.21 +/- 16.6 Hz). As expected, standing, a simple manoeuvre augmenting sympathetic activity, caused a stronger predominance of the low frequency component. We conclude that our method is reliable to evaluate, by means of spectral analysis, rhythmical oscillations of r-r variability.     

Structure-based analysis of protein-RNA interactions using the program ENTANGLE

Until recently, drawing general conclusions about RNA recognition by proteins has been hindered by the paucity of high-resolution structures. We have analyzed 45 PDB entries of protein-RNA complexes to explore the underlying chemical principles governing both specific and non-sequence specific binding. To facilitate the analysis, we have constructed a database of interactions using ENTANGLE, a JAVA-based program that uses available structural models in their PDB format and searches for appropriate hydrogen bonding, stacking, electrostatic, hydrophobic and van der Waals interactions. The resulting database of interactions reveals correlations that suggest the basis for the discrimination of RNA from DNA and for base-specific recognition. The data illustrate both major and minor interaction strategies employed by families of proteins such as tRNA synthetases, ribosomal proteins, or RNA recognition motifs with their RNA targets. Perhaps most surprisingly, specific RNA recognition appears to be mediated largely by interactions of amide and carbonyl groups in the protein backbone with the edge of the RNA base. In cases where a base accepts a proton, the dominant amino acid donor is arginine, whereas in cases where the base donates a proton, the predominant acceptor is the backbone carbonyl group, not a side-chain group. This is in marked contrast to DNA-protein interactions, which are governed predominantly by amino acid side-chain interactions with functional groups that are presented in the accessible major groove. RNA recognition often proceeds through loops, bulges, kinks and other irregular structures that permit use of all the RNA functional groups and this is seen throughout the protein-RNA interaction database.     

A computer program for the analysis of crossover designs.

We describe a program, CROSS, which we have written to obtain potency estimates and other parameters for bioassay data from assays of crossover design. The program permits testing of all assays for statistical validity and calculates the complete analysis of variance for assays of balanced design. The form of data input and the complete documentation of assay results make this program particularly useful for anyone carrying out crossover assays on a routine basis. The analysis of variance presented is also useful for more general biological or medical situations.