Pharmacokinetic curve fitting and parameter determination by non-linear,iterative least squares regression analysis using a programmed minicalculator

A pharmacokinetic non-linear, iterative least-squares program for the minicalculator TI-59 with adapted printer is described. The program utilizes the Gauss-Newton gradient method in an iterative, non-linear regression analysis of up to 18 data pairs. Single-dose plasma concentration data of 5-hydroxytryptophan, theophylline and prednisolone were comparatively analysed using both the described program (called NONTI-59) and Metzlers well-established digital computer program NONLIN.     

Argo: a data analysis program for quantum chemical calculations

Journal of Molecular Modeling - Soft spot analysis helps evaluate the site of the metabolic lability that impacts the bio-availability of the drug. However, given its laborious and time consuming...     

Analysis of variance and Westlake's test of bioavailability data using a programmable minicalculator

A program for the HP-41 CV calculator with adapted printer is described for the analysis of variance of bioavailability data based upon the areas under the curve measured during a two-way cross-over pharmacokinetic study of two different drug formulations. The program can also perform the test of Westlake to compute the 95% confidence interval and determine if both formulations are bioequivalent.     

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.     

UNiquant, a program for quantitative proteomics analysis using stable isotope labeling

Stable isotope labeling (SIL) methods coupled with nanoscale liquid chromatography and high resolution tandem mass spectrometry are increasingly useful for elucidation of the proteome-wide differences between multiple biological samples. Development of more effective programs for the sensitive identification of peptide pairs and accurate measurement of the relative peptide/protein abundance are essential for quantitative proteomic analysis. We developed and evaluated the performance of a new program, termed UNiquant, for analyzing quantitative proteomics data using stable isotope labeling. UNiquant was compared with two other programs, MaxQuant and Mascot Distiller, using SILAC-labeled complex proteome mixtures having either known or unknown heavy/light ratios. For the SILAC-labeled Jeko-1 cell proteome digests with known heavy/light ratios (H/L = 1:1, 1:5, and 1:10), UNiquant quantified a similar number of peptide pairs as MaxQuant for the H/L = 1:1 and 1:5 mixtures. In addition, UNiquant quantified significantly more peptides than MaxQuant and Mascot Distiller in the H/L = 1:10 mixtures. UNiquant accurately measured relative peptide/protein abundance without the need for postmeasurement normalization of peptide ratios, which is required by the other programs.     

Conformational analysis of a novel cyclic enkephalin analogue using NMR and EDMC calculations

Conformational space of a novel cyclic enkephalin analogue, cyclo(N(epsilon),N(epsilon')-carbonyl-D-Lys2,Lys5)enkephalin amide, was exhaustively examined. A large number of conformations was selected and clustered into families on the basis of their structure and energy. For representative conformations ROESY spectra were generated and their linear combination was fitted to the spectra measured in water and Me2SO-d6. This procedure yielded an ensemble of most populated conformations of the peptide in the two solvents.     

Radioimmunoassay data handling and calculations with a graphics-statistics computer program.

This paper discusses the application of the data handling-graphics-statistics program Stata (Computing Resources Center, Santa Monica, CA) to radioimmunoassay. We have found that this program is more powerful and easier to use than a spreadsheet for analyzing various kinds of laboratory data generated from chromatography, radiolabeling experiments, enzyme-linked immunosorbent assays, and radioimmunoassays, to name several examples. Data from a radioimmunoassay procedure, originally analyzed using a spreadsheet, Lotus 1-2-3, have been processed with Stata. Simple programs (batch files) have been devised for computations and graphics. The original data and a comparison of results are presented.     

Immunoregulation in the rat: requirements for in vitro B cell responses to classical TI-1 and TI-2 antigens

The presence of suppressor cells and their mediators has made it difficult to induce B cell mitogenic or immune responses in rat spleen cell cultures. In the present study, we have defined culture conditions required for induction of in vitro thymic independent (TI) immune responses in the rat. Rat spleen cell cultures support low responses to various trinitrophenyl (TNP) haptenated antigens including TNP-Brucella abortus (TNP-BA), TNP-lipopolysaccharide [LPS; either phenol (Ph)- or butanol (Bu)-water extracted], TNP-Ficoll, and TNP-dextran. However, all of these antigens induced good splenic anti-TNP PFC responses when given at appropriate doses in vivo. When spleen cells were depleted of adherent cells and cultured with TI antigens in vitro, good anti-TNP PFC responses were seen with TNP-BA, whereas, lower responses were induced by TNP-LPS (Ph or Bu). No responses were observed in cultures incubated with either TNP-Ficoll or TNP-dextran. Purified splenic B cell cultures [prepared by panning on plates coated with anti-rat F (ab')2] supported good responses to TNP-LPS (Ph or Bu) and TNP-BA. The addition of irradiated splenic adherent cells (macrophages, M phi) to either M phi-depleted or purified B cell cultures completely abrogated in vitro responses to TNP-BA or TNP-LPS (Ph or Bu). Purified splenic B cell cultures generally responded poorly to TNP-Ficoll or TNP-dextran. Addition of indomethacin (IM) to spleen cell cultures abrogated suppression and allowed anti-TNP PFC responses to TNP-BA, TNP-LPS (Ph or Bu), TNP-Ficoll, and TNP-dextran. Furthermore, nude spleen cell cultures treated with IM, also allowed significant TNP-Ficoll and TNP-dextran immune responses; however, untreated cultures did not respond to these antigens. Our studies indicate that rat splenic B cell cultures are responsive to TI antigens, and highest responses occur with the murine TI-1 class, e.g., TNP-BA and TNP-LPS. Inhibition of suppression with IM restored splenic B cell responses to the murine TI-2 class, i.e., TNP-Ficoll and TNP-dextran.     

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 PC program for performing multigroup longitudinal comparisons using the Potthoff-Roy analysis and orthogonal polynomials

A PC-program performing the Potthoff-Roy (PR) multigroup (G-sample) analysis of longitudinal data is described and illustrated. This program and the underlying statistical model are useful in the comparison of several longitudinal samples. Applications include the study of growth, development, adaptation, aging, and treatment effects (in short, any phenomenon in which the passage of time is important) for which serial data are available. Specifically, this method fits polynomials to the average growth curves in the samples, and tests hypotheses concerning the curves themselves and the individual coefficients of the polynomials. The program features the utilization of orthogonal polynomial regression coefficients (OPRCs) and is written in GAUSS, a relatively inexpensive yet comprehensive matrix programming language. It is documented that using OPRCs to comprise the within-individual or time design matrix has several advantages over the more usual choice of the successive-powers-of-t form of this matrix and an example of one important such advantage is provided. GAUSS was employed to make the program readily-accessible (i.e., executable code) to biomedical investigators. The GAUSS compiler is not required to run this program. Information regarding the availability of the program is provided in the Appendix.     

LOGIT: a program for dose-response analysis.

We describe a FORTRAN computer program for fitting the logistic distribution function: (formula: see text) Where x represents dose or time, to dose-response data. The program determines both weighted least squares and maximum likelihood estimates for the parameters alpha and beta. It also calculates the standard errors of alpha and beta under both estimation methods, as well as the median lethal dose (LD50) and its standard error. Dose--response curves found by both fitting methods can be plotted as well as the 95% confidence bands for these lines.     

A computer program using a nested analysis of variance in morphometric sampling

The quality of the sample set is absolutely essential in a morphometric analysis. In this paper a computer program is described which uses a nested analysis of variance in defining the sample. The program denotes those levels of the sampling protocol at which additional sampling should be performed to reduce the variance within the sample set. Furthermore, the program is written for use on a microcomputer which allows it to be used routinely in monitoring a sample set.     

Interactive analysis of phylogeny and character evolution using the computer program MacClade

Computer programs for phylogenetic analysis have been important tools in systematics and evolutionary biology, but most have been designed primarily for the reconstruction of phylogenetic trees and not the interpretation of patterns of character evolution. Described here is the computer program MacClade, designed for interactive analysis of character evolution and phylogeny. For a given tree and a matrix of character data, MacClade displays its reconstruction of character evolution by shading the branches of the tree to indicate ancestral states. Trees can be manipulated for instance by picking up and moving branches. Assumptions underlying the reconstruction of character evolution can be varied extensively. With these manipulations and MacClade's graphical feedback, one can explore the relationships among phylogenetic trees, character data, assumptions and interpretations of character evolution. MacClade has extensive facilities for editing data, displaying various summaries of character evolution in charts and diagrams, and printing.     

mlgsim: a program for detecting clones using a simulation approach

Sexual and asexual forms of plants and animals often coexist in the same population. In such cases, the assessment of genotypic identity among individuals is vital for valid biological interpretation of population and evolutionary processes. Several methods are used for identifying clones based on genetical marker data. The only method that detects which multilocus genotypes are likely to be clones has limitations in statistical power. We present a program (mlg sim) that, using a simulation approach, calculates significance values for the likelihood that a multilocus genotype observed more than once in a population is the result of sexual reproduction.