Non-linear fitting program for biological data

A simple microcomputer program written in Microsoft Basic estimates pharmacokinetic parameters using the coordinate search technique to minimize the sum of squared errors. The program developed for portable computers combines a plot of data and curve fitting so as to find rapidly the initial parameters with the subsequent optimization of the parameter estimate.     

A demonstration of pharmacokinetics and physiological modelling using a microcomputer for data capture and analysis

We describe a simple and inexpensive demonstration of mass transportand exchange using dye clearance from a hydro-dynamic model.A microcomputer was used for data acquisition and storage, non-linearleast squares curve fitting, compartmental analysis and parameterestimation. The system is useful for demonstrating the indicator— dilution technique for fluid volume measurement andcompartmental analysis in pharmacokinetics. Received on August 8, 1986; accepted on September 25, 1986     

Automation of protein assays with a microcomputer interfaced to a spectrophotometer

We have developed a system for semi-automatic protein quantitation assays based on an inexpensive, general-purpose microcomputer. A commercial curve fitting program was modified for direct data input from the spectrophotometer via an analog to digital converter. The software provides specific prompts for protein assays resulting in a rapid and user friendly, semi-automated system. A listing of the protein assay results are printed, or stored to a magnetic disk, along with a graphic representation of the standard curve.     

NKCELPRO: a program for microcomputer applicable to the study of responses of spontaneous cytotoxicity

A microcomputer program (NKCELPRO) which expedites the exact quantification of various parameters referring to NK cell activities is described. The program is written in BASIC language and computes the activities of cell-mediated cytotoxicity by collating and reducing radioactive count data obtained from 51Cr releasing assays. The information generated by this program includes statistics such as the average values, fitting by last square regression line with its correlation coefficient, as well as determination of the percent specific lysis and lytic units/10(7) effector cells according to any reference value previously defined by the operator. Special program features allow for a certain flexibility in the experimental protocol design as well as in the graphic expression of the results. Data storage on a disk with filing purposes for subsequent studies is also available.     

A Pascal program for weighted least squares regression on a microcomputer

Weighted least-squares regression has been programmed in Pascal for a microcomputer. A double precision Pascal compiler and the Motorola 6809 assembler produce a fast machine-code program occupying 22,000 bytes of memory when appended to the Pascal run-time module. Large data sets fit in the remaining memory. A regression with 72 observations and 24 parameters runs in 7 min, excluding optional print out of large matrices. The maximum dimensions of the design matrix, X, can be altered by modifying two Pascal constants. Minor changes to the Pascal source program will make it compatible with other Pascal compilers. The program optionally orthogonalises the X matrix to detect linearly-dependent columns in X, and/or generate orthogonal parameter estimates. After orthogonalizing X and fitting the model, the parameter estimates for the original X can be retrieved by the program. Regressions on a repeatedly reduced model are performed through elimination of columns in X until the minimum adequate model is obtained.     

Einsatz eines Hybridrechnersystems zur Prozeßführung von Antibiotikafermentationen in einer Scale-up-Linie

A hybrid computer completes a scale up line to a computer coupled fermentation (CCF) system for data processing, monitoring and operator servicing, documentation and process control. Presented experiences using this arrangement were adapted and transferred to microcomputer systems.     

Data plotting of warfarin binding to human serum albumin

The binding of warfarin to human serum albumin was studied by equilibrium dialysis at pH 7.4 in a 67 mM sodium phosphate buffer at 37 degrees C. The equilibrium data were analysed using a computer program for curve fitting. The analysis was made fitting the data to equations for one, two and three classes of binding sites with one, two and three sites at the primary binding site (n(1)=1, 2 or 3). The data fitting was acceptable for two and three classes of binding sites but the best fit was obtained with the equation for two classes of binding sites, allowing us to define the binding by a model with two independent classes of binding sites on the serum albumin molecule.     

Collection and analysis of kinetic data from a stopped-flow spectrophotometer using a microcomputer

A method of interfacing an inexpensive microcomputer to a stopped-flow kinetics spectrophotometer is described. It allows software-selectable sampling frequencies between 0.1 ms and 8 s and large numbers of data points to be collected. Machine language routines to use the interface are described and these allow the sampling frequency to be altered during data collection to ensure adequate numbers of points in critical regions of the kinetic profile. BASIC programs for collection and analysis of multicomponent kinetic data using this system are also described. Due to the large number of data points that can be collected and the ability to selectively sample transmittance values in regions where the signal is rapidly changing with time, relatively unsophisticated methods of data analysis can be used. These methods are suitable for use by microcomputers and mean that data analysis and acquisition can be performed on the same microcomputer in real time. To illustrate this, multicomponent analysis of kinetic transients is performed on simulated data and on the dissociation kinetics of the ethidium-DNA complex.     

Symmetry-restrained flexible fitting for symmetric EM maps

Many large biological macromolecules have inherent structural symmetry, being composed of a few distinct subunits, repeated in a symmetric array. These complexes are often not amenable to traditional high-resolution structural determination methods, but can be imaged in functionally relevant states using cryo-electron microscopy (cryo-EM). A number of methods for fitting atomic-scale structures into cryo-EM maps have been developed, including the molecular dynamics flexible fitting (MDFF) method. However, quality and resolution of the cryo-EM map are the major determinants of a method's success. In order to incorporate knowledge of structural symmetry into the fitting procedure, we developed the symmetry-restrained MDFF method. The new method adds to the cryo-EM map-derived potential further restraints on the allowed conformations of a complex during fitting, thereby improving the quality of the resultant structure. The benefit of using symmetry-based restraints during fitting, particularly for medium to low-resolution data, is demonstrated for three different systems.     

Fitting conditional survival models to meta-analytic data by using a transformation toward mixed-effects models

Summary .   Frailty models are widely used to model clustered survival data. Classical ways to fit frailty models are likelihood-based. We propose an alternative approach in which the original problem of "fitting a frailty model" is reformulated into the problem of "fitting a linear mixed model" using model transformation. We show that the transformation idea also works for multivariate proportional odds models and for multivariate additive risks models. It therefore bridges segregated methodologies as it provides a general way to fit conditional models for multivariate survival data by using mixed models methodology. To study the specific features of the proposed method we focus on frailty models. Based on a simulation study, we show that the proposed method provides a good and simple alternative for fitting frailty models for data sets with a sufficiently large number of clusters and moderate to large sample sizes within covariate-level subgroups in the clusters. The proposed method is applied to data from 27 randomized trials in advanced colorectal cancer, which are available through the Meta-Analysis Group in Cancer.     

A low-cost chromatograph data-collection system

A data collection system has been constructed, based on the low-cost BBC microcomputer, which provides for the digitization and storage of the data from one or more g.l.c. or h.p.l.c. instruments, or from other data sources with similar data rates. The data can be observed during collection on the graphics screen, and are then stored on disk for subsequent processing. This processing is designed to be interactive, so that the operator can influence decisions about base-line drifts, peak separations, etc. when integrating the peaks, and can decide which peaks are to be stored in a time/intensity record, on the basis of a visual display of the trace. A low cost multi-channel precision ADC, using isolated voltage-to-frequency transducers sited at the sources of data, and multiple counters at the computer, may be used to measure several signals simultaneously even when they originate at some distance from the computer, and extra memory can also be added to the BBC microcomputer to allow temporary storage of data. The software is written in machine code (for the data collection) and BASIC (for the analysis routines) so that modifications to the latter routines can be made easily. The user interface is suitable for routine users who have no computing experience.     

A description of micro- and mainframe-computer programs to summarize frequency,duration and sequences of behavior

Computer programs were developed to hasten the summarization of behavioral data. Behavioral data may be collected by hand (pencil, paper and watch), strip-chart mechanical event recorder, electronic event recorder or by a computer. These behavioral data, in raw form, enter (electronically or manually) a microcomputer (IBM-PC, 128K) or mainframe computer. The microcomputer version summarizes the number of occurrences (frequency), duration and sequence of each behavior. As a microcomputer memory is limited, a program to summarize larger data sets containing more behavior patterns was developed on our mainframe computer (CDC Cyber 730/760). This sequential analysis program can accumulate up to 10 behavioral sequences (9 orders of transition) of up to 50 behaviors in a data set containing up to 10 000 elements. The computer-summary of each treatment may be combined to determine if treatment differences exist. An example data set is provided.     

Chemotactic Behavior of Nematodes

Nematode chemoreception is reviewed Methods that have been used to measure chemotaxis are discussed and a new method using a video camera interfaced to a microcomputer is briefly described. The chemical stimuli that have been identified are discussed. The transition from attractant to repellent as NaCl increases in concentration is demonstrated by new data.     

Microcomputer programs for DNA sequence analysis.

Computer programs are described which allow (a) analysis of DNA sequences to be performed on a laboratory microcomputer or (b) transfer of DNA sequences between a laboratory microcomputer and another computer system, such as a DNA library. The sequence analysis programs are interactive, do not require prior experience with computers and in many other respects resemble programs which have been written for larger computer systems (1-7). The user enters sequence data into a text file, accesses this file with the programs, and is then able to (a) search for restriction enzyme sites or other specified sequences, (b) translate in one or more reading frames in one or both directions in order to find open reading frames, or (c) determine codon usage in the sequence in one or more given reading frames. The results are given in table format and a restriction map is generated. The modem program permits collection of large amounts of data from a sequence library into a permanent file on the microcomputer disc system, or transfer of laboratory data in the reverse direction to a remote computer system.     

Kinetic modeling of sporulation and product formation in stationary phase by Bacillus coagulans RK-02 vis-à-vis other Bacilli

A logistic kinetic model was derived and validated to characterize the dynamics of a sporogenous bacterium in stationary phase with respect to sporulation and product formation. The kinetic constants as determined using this model are particularly important for describing intrinsic properties of a sporogenous bacterial culture in stationary phase. Non-linear curve fitting of the experimental data into the mathematical model showed very good correlation with the predicted values for sporulation and lipase production by Bacillus coagulans RK-02 culture in minimal media. Model fitting of literature data of sporulation and product (protease and amylase) formation in the stationary phase by some other Bacilli and comparison of the results of model fitting with those of Bacillus coagulans helped validate the significance and robustness of the developed kinetic model.     

Computerized continuous monitoring of cytochemical enzyme reaction product formation by the Vickers M85A microdensitometer

Summary An experimental set-up for the continuous monitoring of cytochemical enzyme reaction rates is described. The design consists of a 32K Commodore PET microcomputer, upgraded to Basic 4 and containing a graphics facility. The microcomputer is interfaced with a Vickers M85A microdensitometer, which has been modified and equipped with a Zeiss X63 water immersion objective. The software allows for the automatic transfer of density readings from the M85A to the microcomputer, and for the continuous monitoring of the enzyme reaction as its proceeds at short time intervals (i.e. down to 3.3 s). The relationship between the absorbance change of the enzyme final reaction product and time is printed both numerically and graphically. Initial velocity rates are calculated by regression analysis, and statistical evaluation of grouped data is possible.     

A computer based culturing system for measuring the photosynthetic response of phytoplankton to a fluctuating environment

A microcomputer-controlled culturing system developed to simulate temperature and salinity fluctuations in an estuary is described. The system consists of a microcomputer, interfacing hardware, a continuous culture apparatus, and system software. The system can regulate the temperature and salinity of a continuous phytoplankton culture based on user-defined models of the physical environment and particle transport in a natural environment. The microcomputer also provides efficient data acquisition and data storage. The system was designed to facilitate expansion and modification and can easily be adapted to accomodate various studies of phytoplankton production. Details of a simulation and representative data are presented.     

Microcomputer interface for computer-assisted enzyme kinetic studies with uv-vis spectrophotometers

A simple microcomputer interface, consisting of only three integrated chips, for the input of digitized data from a uv-vis spectrophotometer is described. The interface multiplexes four binary-coded decimal digits, four possible decimal point positions, and an algebraic sign into a single eight-bit parallel input port of the microcomputer. The interface design is also adaptable in a general fashion to any analytical instrument which can present digitized data, with the expansion capability of accommodating more than the number of digits and decimal positions noted in this specific example. Software developed specifically to drive the interface and several general applications to computer-assisted kinetic studies are discussed.     

A microcomputer interface for a digital audio processor-based data recording system.

An inexpensive interface is described that performs direct transfer of digitized data from the digital audio processor and video cassette recorder based data acquisition system designed by Bezanilla (1985, Biophys. J., 47:437-441) to an IBM PC/XT microcomputer. The FORTRAN callable software that drives this interface is capable of controlling the video cassette recorder and starting data collection immediately after recognition of a segment of previously collected data. This permits piecewise analysis of long intervals of data that would otherwise exceed the memory capability of the microcomputer.