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PromH: Promoters identification using orthologous genomic sequences.

Accurate prediction of promoters is fundamental for understanding gene expression patterns, cell specificity and development. In the studies of conserved features of regulatory regions of orthologous genes, it was observed that major promoter functional components such as transcription start points, TATA-boxes and regulatory motifs, are significantly more conservative than the sequences around them (70-100% compared with 30-50%). To improve promoter identification accuracy, we employed these findings in a new program, PromH, created by extending the TSSW program feature set. PromH uses linear discriminant functions that take into account conservation features and nucleotide sequences of promoter regions in pairs of orthologous genes. The program was tested on two sets of pairs of orthologous, mostly human and rodent, sequences with known transcription start sites (TSS), annotated to have TATA (21 genes, 11 orthologous pairs) and TATA-less (38 genes, 19 pairs) promoters, respectively. The program correctly predicted TSS for all 21 genes of the first set with a median deviation of 2 bp from true site location. Only for two genes, was there significant (46 and 105 bp) discrepancy between predicted and annotated TSS positions. For 38 TATA-less promoters from the second set, TSS was predicted for 27 genes, in 14 cases within 10 bp distance from annotated TSS, and in 21 cases--within 100 bp distance. Despite more discrepancies between predicted and annotated TSS for genes from the second set, these results are consistent with observations of much higher occurrence of multiple TSS in TATA-less promoters. In any case, our results show that PromH identifies TSS positions significantly more accurately than any other published promoter prediction method. The PromH program is available at http://www.softberry.com/berry.phtml?topic=promh.

Animals↗

MicroPharm-K, a microcomputer interactive program for the analysis and simulation of pharmacokinetic processes.

PURPOSE: The microcomputer program, MicroPharm-K (MP-K) was developed for pharmacokinetic modeling, including analysis of experimental data and estimation of relevant parameters, and simulation. The intention was to provide a user-friendly, interactive, event-driven program for PC computers. METHODS: The data are ascribed to a predefined model from a library including various routes of administration, oral or intra-venous, bolus or infusion, and various compartmental interpretations, 1 to 3. Single and multiple administrations are supported. The program provides initial estimates of the parameters in most cases, and the parameters are then fitted to the model by non linear model fitting using either the Simplex, Evol, Gauss-Newton, Levenberg-Marquardt or Fletcher-Powell algorithms. The non linear model fitting is based on the maximum likelihood method, and the criterion to minimize is either the weighted least squares (Chi 2 criterion) or the extended least squares. Graphical representations of non-fitted or curve-fitted data are immediately available (including log-scale representation), as well as pharmacokinetic typical parameters such as area under the curve, clearance, volumes, time-rate constants, transfer rate constants, etc. RESULTS: Simulated and experimental data were analysed and the results were similar to those obtained by other programs. CONCLUSIONS: This non linear fitting program has been proved in our laboratory to be a very effective package for pharmacokinetic studies, including estimation and simulation. Because it is easy-to-use and runs on basic computers, the program could also be used for educational purposes.

Administration, Oral↗

Program structure and continuity of mental health care.

Continuity has been a much discussed but under-researched objective of mental health care, in part due to measurement challenges. A small body of research has identified program features associated with continuity, based on measures of service use. A recent planning project provided an opportunity to examine the effects of these features on continuity using a new self-report continuity measure. Nine program features were measured and linear regression analyses were used to assess the relationship between these features and continuity, controlling for client characteristics. Client continuity was higher in programs that offered some night or weekend coverage and lower in programs that provided more care in the community. This latter finding was unexpected and may represent program efforts to engage individuals experiencing difficulties with service access. The association between each of the other 7 program features and continuity was not significant. Possible explanations for this finding are explored.

Community Mental Health Services↗

Steady state enzyme kinetics: experimental design and data analysis by microcomputer.

One of the most time-consuming, yet essential, operations involved in the steady state kinetic study of enzymes is the design and optimization of experimental conditions. A computer program was developed for the Sinclair ZX-81 (or TS-1000, 1500) microcomputer which will optimize substrate concentration for preliminary and subsequently more refined kinetic analysis of one, two or three substrate systems. This program also analyzes the data collected from these studies by linear regression, weighted linear regression or weighted non-linear regression. In addition to the above program several of the enzyme kinetic statistical analysis programs of Cleland (1979) have been translated from FORTRAN into BASIC and implemented on the ZX-81 and the TRS-80 model II. Inexpensive commercially available software was used to overcome the inability of the ZX-81 to read data files from magnetic tape making the data analysis programs easier to use.

Computers↗

CLONE 3: plasmid drawing and clone management software program for microcomputers.

CLONE 3 is a microcomputer software program which draws circular and linear plasmid maps, facilitates cloning operations and performs related sequence analysis and information retrieval functions. This article describes the use of the CLONE 3 program to streamline the flow of information in the research laboratory doing genetic engineering applications.

Base Sequence↗

Nonlinear SPICE models for physiologic systems.

Most biological systems are nonlinear but investigators interested in modeling them often make linear approximations to avoid performing tedious manual calculations. SPICE (Simulation Program with Integrated Circuit Emphasis, developed at the University of California, Berkeley, CA), an electrical circuit simulation program, is frequently used for creating and analyzing linear network models of physiologic and pathophysiologic processes. However, few investigators use the full capabilities of the program by modeling nonlinear elements. We developed six nonlinear SPICE elements, allowing simplified modeling of most commonly encountered physiologic processes. These are provided as subcircuits that can be easily incorporated into existing SPICE models. Included are voltage and current controlled nonlinear resistors, capacitors and inductors. In addition, we describe adders, multipliers, powers, inverse, and derivative functions.

Computer Simulation↗

Looping dynamics of linear DNA molecules and the effect of DNA curvature: a study by Brownian dynamics simulation.

A Brownian dynamics (BD) model described in the accompanying paper (Klenin, K., H. Merlitz, and J. Langowski. 1998. A Brownian dynamics program for the simulation of linear and circular DNA, and other wormlike chain polyelectrolytes. Biophys. J. 74:000-000) has been used for computing the end-to-end distance distribution function, the cyclization probability, and the cyclization kinetics of linear DNA fragments between 120 and 470 basepairs with optional insertion of DNA bends. Protein-mediated DNA loop formation was modeled by varying the reaction distance for cyclization between 0 and 10 nm. The low cyclization probability of DNA fragments shorter than the Kuhn length (300 bp) is enhanced by several orders of magnitude when the cyclization is mediated by a protein bridge of 10 nm diameter, and/or when the DNA is bent. From the BD trajectories, end-to-end collision frequencies were computed. Typical rates for loop formation of linear DNAs are 1.3 x 10(3) s(-1) (235 bp) and 4.8 x 10(2) s(-1) (470 bp), while the insertion of a 120 degree bend in the center increases this rate to 3.0 x 10(4) s(-1) (235 bp) and 5.5 x 10(3) s(-1) (470 bp), respectively. The duration of each encounter is between 0.05 and 0.5 micros for these DNAs. The results are discussed in the context of the interaction of transcription activator proteins.

Biophysics↗

A new implemented version of program MIR (MIR II): analysis and identification of mathematical models in enzyme and transport kinetic studies.

The computer program MIR previously described (R. Bianchi, G.M. Hanozet and M. Pilone Simonetta, Comput. Prog. Biomed. 16 (1983) 189) that fits trial rate laws to enzyme and transport steady-state kinetic data by the least-squares method has been enhanced. The new version MIR II is an interactive program and it consists of five major routines and a larger number of smaller program elements to perform the linear (three different functional forms) and non-linear (eleven mathematical models) regression analysis of kinetic data from enzyme and transmembrane transport experiments, also in the presence of inhibitors. Other features of the new program include a set of statistics and tests useful for the model building process, for the development of the mathematical model and for its validation and maintenance. An algorithm for fitting a straight line taking into account errors in both x and y is also provided.

Algorithms↗

Image processing and enhancement provided by commercial dental software programs.

OBJECTIVES: To identify and analyse methods/algorithms for image processing provided by various commercial software programs used in direct digital dental imaging and to map them onto a standardized nomenclature. METHODS: Twelve programs presented at the 28th International Dental-Show, March, 2001, Cologne, Germany and the Emago advanced software were included in this study. An artificial test image, comprised of gray scale ramps, step wedges, fields with Gaussian-distributed noise, and salt and pepper noise, was synthesized and imported to all programs to classify algorithms for display; linear, non-linear and histogram-based point processing; pseudo-coloration; linear and non-linear spatial filtering; frequency domain filtering; measurements; image analysis; and annotations. RESULTS: The 13 programs were found to possess a great variety of image processing and enhancement facilities. All programs offer gray-scale image display with interactive brightness and contrast adjustment and gray-scale inversion as well as calibration and length measurements. While Emago enables arbitrary spatial filtering with user-defined masks up to 7x7 pixels in size, most programs sparsely include filters and tools for image analysis and comparison. Moreover, the naming and implementation of provided functions differ. Some functions inappropriately use standardized image processing terms to describe their operations. CONCLUSIONS: Image processing and enhancement functions are rarely incorporated in commercial software for direct digital imaging in dental radiology. Until now, comparison of software was limited by the arbitrary naming used in each system. Standardized terminology and increased functionality of image processing should be offered to the dental profession.

Algorithms↗

Predictors of systolic blood pressure response to treadmill exercise: the Lipid Research Clinics Program Prevalence Study.

We used multiple linear regression to study predictors of systolic blood pressure response (SBPR), i.e., the increase in pressure above baseline after 3, 6, and 9 min of treadmill exercise, in 4262 men and women. Predictors considered were usual SBP, the difference (delta SBP) between resting SBP and SBP immediately before exercise, age, education, obesity index, alcohol consumption, cigarette smoking, preexercise heart rate and, in women, gonadal hormone use. In men, age, obesity index, and cigarette smoking were positively associated with SBPR and in women 20 to 49 years old, age, obesity index, and alcohol consumption were positively associated with SBPR. In women 50 years old or older, usual SBP was negatively associated with SBPR. In both men and women a larger delta SBP was associated with a smaller SBPR. These results help explain the considerable variation in SBPR, and the delta SBP results suggest that potential SBPR may, to certain extent, have a specific, finite range. The similarity of predictor variables for SBPR to predictor variables for hypertension is concordant with the previous observation that a high SBPR may foreshadow subsequent hypertension.

Adult↗

[Estimating cost functions of cancer screening programs provided by municipalities].

OBJECTIVE: To estimate cost functions of cancer screening programs for stomach, lung, colorectal, cervical, and breast cancers provided by municipalities and to describe the relationship between the costs and the scale of cancer screening programs. METHODS: Subjects were all the municipalities in Japan. Questionnaires were sent to 3,182 subjects and 1,860 responses were received. Data obtained from questionnaires were the number of persons screened and the total cost of each program in the 1998 fiscal year. A cost function of each program was specified as a linear model, a power model, and a cubic model, and the fitness of each model was estimated. RESULTS: Long-run cost functions of all the cancer screening programs allowed better explanation of the relationship between the number of persons screened and the total cost than short-run cost functions. The average costs of stomach, colorectal, and cervical cancer screening programs increased and the average cost of the lung cancer screening program decreased, as the number of persons screened increased. The cost function of the breast cancer screening program could not be identified. CONCLUSIONS: It is necessary to estimate not only cost functions but also production functions of cancer screening programs using the data related to products, costs, and factors of production to evaluate the efficiency of cancer screening programs.

Cities↗

Amperometric pH regulation--a flexible tool for rapid and precise temporal control over the pH of an electrolyte solution.

Temporal control over both pH and ionic strength of an electrolyte solution with high accuracy was achieved with a dynamic, computer feedback-controlled amperometric pH-stat device consisting of four pH-regulating electrodes placed in electrolyte reservoirs that are separated by dialysis membranes from a central compartment. Theoretical predictions of the behavior of this arrangement, obtained by computer simulation, were validated by running temporal pH programs such as step functions, oscillations, and linear pH gradients. Deviations from nominal values given by the computer program are within the limits of accuracy of the pH-measuring electrodes. No volume changes accompany a change of pH or conductivity since ions are forced to leave or enter the central compartment through the membranes by the electrical force applied between the pH-regulating electrodes. The device is flexible, easy to use and easily miniaturized. We discuss a wide range of possible applications in biochemistry and cell science. These include automated pH adjustment, isoelectric protein separation, amperometric measurement of enzyme kinetics and the response of cell cultures to well-defined pH changes.

Computer Simulation↗

Vitamin A-fortified monosodium glutamate and health, growth, and survival of children: a controlled field trial.

In a controlled trial, fortification of commercially marketed monosodium glutamate (MSG) with vitamin A improved serum vitamin A levels of young children and the vitamin A content of breast milk of lactating women. These improvements in vitamin A indices were accompanied by dramatic changes in health and anthropometric status. During the course of the study, the prevalence of Bitot's spots among children in program villages fell progressively from 1.2% at base line to 0.2% 11 mo after introduction of the fortified product (p less than 0.001); xerophthalmia rates in control villages remained essentially unchanged. Linear growth was greater among program than among control children at every age. Hemoglobin levels among program children rose by approximately 10 g, from 113 +/- 16 g/L at base line to 123 +/- 16 by 5 mo (p less than 0.001); they remained essentially unchanged among children of control villages. Preschool children in control villages died at 1.8 times the rate of children in program villages.

Anthropometry↗

Practical multipeptide synthesis: dedicated software for the definition of multiple, overlapping peptides covering polypeptide sequences.

A personal computer program for the conversion of linear amino acid sequences to multiple, small, overlapping peptide sequences has been developed. Peptide lengths and "jumps" (the distance between two consecutive overlapping peptides) are defined by the user. To facilitate the use of the program for parallel solid-phase chemical peptide syntheses for the synchronous production of multiple peptides, amino acids at each acylation step are laid out by the program in a convenient standard multi-well setup. Also, the total number of equivalents, as well as the derived amount in milligrams (depend-ending on user-defined equivalent weights and molar surplus), of each amino acid are given. The program facilitates the implementation of multipeptide synthesis, e.g., for the elucidation of polypeptide structure-function relationships, and greatly reduces the risk of introducing mistakes at the planning step. It is written in Pascal and runs on any DOS-based personal computer. No special graphic display is needed.

Amino Acid Sequence↗

High-speed liquid chromatograhic separation of glycerides, fatty acids and sterols.

The high-speed liquid chromatographic separation and detection of triglycerides, diglycerides, fatty acid and sterols was carried out to permit the analyses of total lipids from soybeans and soybean food. The study was conducted with a Varian Aerograph LC 1200 liquid chromatograph equipped with a hydrogen flame ionization detector. Linear-gradient, solvent-flow programming was used. Separation of the total lipids by the gradient was achieved in 30 minutes and the column prepared for the next analysis by washing with solvents. The detector response curves for authentic compounds were linear and equivalent to within 2.3% error, based on the response to 1-monopalmitin. The minimum detectable amounts of the authentic substances were between 0.1 and 1.4mug. When a three-stranded wire was used instead of single filament wire, the sensitivity was increased by 37%.

Chromatography, High Pressure Liquid↗

A FORTRAN program for testing trend and homogeneity in proportions.

A FORTRAN program is provided for testing linear trend and homogeneity in proportions. Trend is evaluated by the Cochran-Armitage method and homogeneity is tested by an overall X2 test as well by multiple pairwise comparisons by the Fisher-Irwin exact method. The program should be easy to implement on any size of computer with a FORTRAN compiler.

Biometry↗

A semi-micromethod for the determination of the extinction coefficients of duplex and single-stranded DNA.

We have developed a rapid and convenient procedure for the determination of concentrations and extinction coefficients of oligo- and polynucleotides. It offers significant advantages over other methods in terms of precision and the ability to detect artifactual or erroneous results. Samples are first completely digested with appropriate enzymes to mononucleotides and nucleosides. Using the multicomponent linear regression capabilities of commonly available spreadsheet programs, the absorbance spectrum of the digest can be analyzed as a linear combination of the contribution of the possible constituent monomers. If all the spectral components present have been included, the analysis yields the concentration of each of the monomer species whose sum is the concentration (in monomer units) of the original undigested sample. When combined with the predigest absorbance spectrum, the extinction coefficients of the intact sample can then be calculated. The analysis also yields the fractional base composition of the oligomer or polymer. The extensive spectral data provided by digital read-outs of modern spectrophotometers permit the application of sensitive tests of the goodness of fit, thus facilitating the detection of artifacts and sample inhomogeneity. Both single-strand and duplex structures can be analyzed comfortably in sample sizes of 25 to 35 nmol (total) of mononucleotides with a precision of 1%. The concentrations obtained by this method agree, on the average, within 0.2% with those determined by phosphate analysis of the same sample. The method also yields the base composition with an accuracy of ca. 5% for high-molecular-weight polymers and 2% for short oligomers (15-20 bp) when compared to the predicted values.

Base Composition↗

DOMPLOT: a program to generate schematic diagrams of the structural domain organization within proteins, annotated by ligand contacts.

A program is described for automatically generating schematic linear representations of protein chains in terms of their structural domains. The program requires the co-ordinates of the chain, the domain assignment, PROSITE information and a file listing all intermolecular interactions in the protein structure. The output is a PostScript file in which each protein is represented by a set of linked boxes, each box corresponding to all or part of a structural domain. PROSITE motifs and residues involved in ligand interactions are highlighted. The diagrams allow immediate visualization of the domain arrangement within a protein chain, and by providing information on sequence motifs, and metal ion, ligand and DNA binding at the domain level, the program facilitates detection of remote evolutionary relationships between proteins.

Adenosine Diphosphate↗