Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Programming, Linear”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1990

Information content of the multibreath nitrogen washout: effects of experimental error.

Methods that recover a continuous distribution of specific ventilation (ventilation-to-volume ratio, VA/V) from the multibreath N2 washout curve theoretically can resolve up to four modes of ventilation and reveal the major characteristics of the underlying distribution if experimental error is absent. This paper quantitatively assesses the effects of experimental error on resolution. The washout curves from five typical distributions were studied using linear programming and Monte Carlo methods. A measurement error of 0.1% was assumed in the mixed-expired N2 signal. Only 7 of the first 17 breaths contribute independent information about the underlying distribution, and only rough resolution of the underlying distribution is possible in the presence of error. Only two modes of ventilation plus an estimate of dead space can be confidently resolved. It is not possible to separate VA/V greater than 10 from dead space. A 10-fold reduction in experimental error will not greatly improve resolution. Experimental error, by reducing the linear independence of the defining kernels, significantly limits the information content and resolution of the multibreath N2 washout.

Humans↗
PubMed1988

Computer-assisted semen analysis: evaluation of method and assessment of the influence of sperm concentration on linear velocity determination.

Semen samples from 77 men were used to estimate the accuracy and precision of measurements of sperm density, percent motility, and motion characteristics using a new, fully automated, computer-assisted semen analyzer (CASA). Results are compared with traditional semen analysis methodology. Acceptable precision for count and percent motility was obtained using three to nine random fields of observation when there were more than 10 cells per high-power microscopic field. A highly significant correlation (P less than 0.01) was found between the two methods in the assessment of sperm concentration and percent motility, but CASA overestimated concentration significantly (P less than 0.01) by about 30% when there were less than 60 cells per high power field. This overestimation seemed to be due to the number of nonsperm particles in semen that are confused with spermatozoa by the program. Linear velocity determination was influenced by the number of tracking points as well as by the concentration of cells present in the counting chamber. More representative linear velocity estimations in semen were obtained when sperm concentration was less than 40 x 10(6) cells/ml and 20 tracking points were used in the determination. For semen specimens containing higher cell density, sperm concentration needed to be reduced by diluting the semen with the patient's own sperm-free seminal plasma before measuring motion characteristics.

Computers↗
PubMed1988

Analysis and measurement of neck loads.

To examine the loads imposed on the structures of the neck by the performance of physical tasks, a biomechanical model of the neck was constructed. The model incorporated 14 bilateral pairs of muscle equivalents crossing the C4 level. A double linear programming optimization scheme that minimized maximum muscle contraction intensity and then vertebral compression force while equilibrating external loads was used to calculate the muscle contraction forces required and the motion segment reactions produced by task performance. To test model validity, 14 healthy adult subjects performed a series of isometric tasks requiring use of their neck muscles. These tasks included exertions in attempted flexion, extension, and left and right lateral bending and twisting. Subjects exerted maximum and submaximum voluntary efforts. During the performance, surface myoelectric activities were recorded at eight locations around the periphery of the neck at the C4 level. Calculated forces and measured myoelectric activities were then linearly correlated. Mean measured voluntary neck strengths in 10 male subjects were as large as 29.7 Nm. Four female subjects developed mean strengths that were approximately 60%-90% of those of the males. In both sexes, neck muscle strengths were approximately one order of magnitude lower than previously measured lumbar trunk strengths. Mean calculated neck muscle contraction forces ranged to 180 N. Mean calculated compression forces on the C4-5 motion segment ranged to 1164 N, lateral shear forces ranged to 125 N, and anteroposterior shear forces ranged to 135 N. Correlation coefficients between the calculated muscle forces and the measured myoelectric activities were as large as 0.85 in some muscles, but generally were smaller than this.

Adult↗
PubMed2006

A hybrid Newton-type method for censored survival data using double weights in linear models.

As an alternative to the Cox model, the rank-based estimating method for censored survival data has been studied extensively since it was proposed by Tsiatis [Tsiatis AA (1990) Ann Stat 18:354-372] among others. Due to the discontinuity feature of the estimating function, a significant amount of work in the literature has been focused on numerical issues. In this article, we consider the computational aspects of a family of doubly weighted rank-based estimating functions. This family is rich enough to include both estimating functions of Tsiatis (1990) for the randomly observed data and of Nan et al. [Nan B, Yu M, Kalbfleisch JD (2006) Biometrika (to appear)] for the case-cohort data as special examples. The latter belongs to the biased sampling problems. We show that the doubly weighted rank-based discontinuous estimating functions are monotone, a property established for the randomly observed data in the literature, when the generalized Gehan-type weights are used. Though the estimating problem can be formulated to a linear programming problem as that for the randomly observed data, due to its easily uncontrollable large scale even for a moderate sample size, we instead propose a Newton-type iterated method to search for an approximate solution of the (system of) discontinuous monotone estimating equation(s). Simulation results provide a good demonstration of the proposed method. We also apply our method to a real data example.

Carcinoma↗
PubMed1999

PHYSEAN: PHYsical SEquence ANalysis for the identification of protein domains on the basis of physical and chemical properties of amino acids.

MOTIVATION: PHYSEAN predicts protein classes with highly variable sequences on the basis of their physical, chemical and biological characteristics such as diverse hydrophobicity, structural propensity and steric properties. These characteristics, calculated from multiple positions in a sequence, may be conserved even between sequences that fail to produce alignments at any acceptable level of statistical significance. PHYSEAN complements methods that require sequence alignments (BLAST, FASTA, dynamic programming) by adding less residue- and position-specific physicochemical information on the protein or the domain. RESULTS: We predict proteins or their domains like signal peptides using physical, chemical, geometric, and biological properties of the 20 amino acids. This comprehensive set of properties may cover the diagnostic functional and structural aspects of a domain or a protein class. We automatically select and weight a subset of properties so as to discriminate between, e.g., signal peptides and amino-termini of cytosolic proteins with the lowest number of incorrect predictions. This optimal selection of properties and their weights significantly decreases the number of incorrect predictions as compared to any single property or any combination of unweighted properties. Weights have been optimized by high-performance linear programming models that systematically find the optimal solution from among an astronomic number of property/weight combinations. PHYSEAN's performance is demonstrated by highly accurate predictions of signal peptides (the vehicles for protein transport across membranes) and their cleavage sites. The results indicate reliable predictions are possible even in the lack of sequence conservation using an automated physical and chemical analysis of proteins.

Algorithms↗
PubMed1988

Rehabilitation of the patient with chronic back pain. A search for outcome predictors.

This prospective study was initiated 3 years ago to evaluate the outcome and to identify predictors of success or failure in patients admitted to a rehabilitation program for chronic low-back pain. Multiple parameters were evaluated, including psychologic data (MMPI, personal interview, pain drawing, etc.), physical measurements (flexibility, strength and endurance), and demographic data concerning the patient's home and working environment. Information was available on each patient admitted to the program prior to his admission, at completion of the program, 6 weeks following completion of the program and 3 months following completion of the program. A telephone interview was carried out 2 1/2 years following the patient's discharge from the program. Linear regression analysis was used to identify the important independent variables with regard to the dependent variables of relief of back pain, return to work and increased activities at home. Demographic data were of no value as a predictor with the exception of age and returning to work. The patients over the age of 50 returned to work with much less frequency than those less than 50. Psychologic information from the MMPI and similar tests were of no value. The personal preadmission interview of a trained psychologist, however, was a good predictor of an individual's eventual return to work and overall improvement. Worker's Compensation and other litigation was a negative factor in a patient's prognosis. The treatment team's prognosis at the time of discharge from the program was the best overall predictor of a patient's chance of success or failure in the longterm.

Activities of Daily Living↗
PubMed1993

A modeling approach to hospital location for effective marketing.

This paper develops a mixed integer linear programming model for locating health care facilities. The parameters of the objective function of this model are based on factor rating analysis and grid method. Subjective and objective factors representative of the real life situations are incorporated into the model in a unique way permitting a trade-off analysis of certain factors pertinent to the location of hospitals. This results in a unified approach and a single model whose credibility is further enhanced by inclusion of geographical and demographical factors.

Algorithms↗
PubMed1994

Economic comparison of nutritional management strategies for Venezuelan dual-purpose cattle systems.

Objectives of this study were to compare three nutritional management strategies for dual-purpose herds in Venezuela in 1987 using a deterministic, multiperiod linear programming model of a representative farm. The model maximized discounted net margin (total revenues minus variable costs) from the herd for a 3-yr cow replacement cycle partitioned into six periods. The periods accounted for seasonal variation in forage availability and quality, and the model provided information about optimal animal inventories, animal sales, land in forage, and feed supplements. We compared current nutritional management practices and alternatives allowing optimal supplementation with commercial concentrate, molasses, cassava root, and urea. Iteration between the programming model and results from the Cornell Net Carbohydrate and Protein System assured technical coefficients consistent with predicted animal performance. Compared with management practices relying on commercial concentrate, optimal use of molasses and urea permitted increases in the stocking rate. Productivity and profit were restricted primarily by energy intake, which was constrained by intakes of NDF and DM. Alternative management strategies changed the relative importance of nutrient requirements and feed intake constraints. Thus, optimal interventions to alleviate nutritional constraints will vary with current management. Mobilizing adipose and protein tissues during lactation was optimal for most strategies. Supplementing with molasses and urea instead of commercial concentrate was the most profitable strategy, increasing herd net margin by 16% compared to the predominant feeding strategy in the late 1980s.

Adipose Tissue↗
PubMed1993

A Macintosh BASIC program for fitting linear additive models to data by weighted least squares methods, with automatic elimination of redundant parameters from the model.

A BASIC program for fitting linear additive models to data with weighted or unweighted least squares methods and matrix procedures is described. Written and compiled to run on Macintosh II type machines (68020/68030/68040) with coprocessor (68881/68882), the program fits the model supplied by the user as an X or design matrix and provides the option of making the model's parameters orthogonal. Predicted values plus regression and residual terms are calculated. For the weighted fit, the significance of the residual term is evaluated and redundant parameters sequentially and automatically removed until a minimum adequate model is achieved. An appropriate design matrix allows weighted fitting of models for multiway analyses of variance (e.g. factorial, nested and split plot), simple or multiple linear or curvilinear regression, combinations of these in covariance analyses, and genetic analyses (including diallel cross analyses). Sums of squares for individual parameters and orthogonal comparisons can be calculated by the program.

Least-Squares Analysis↗
PubMedDate not supplied

Optimal allocation of resources across four interventions for type 2 diabetes.

BACKGROUND: Several interventions can be applied to prevent complications of type 2 diabetes. This article examines the optimal allocation of resources across 4 interventions to treat patients newly diagnosed with type 2 diabetes. The interventions are intensive glycemic control, intensified hypertension control, cholesterol reduction, and smoking cessation. METHODS: A linear programming model was designed to select sets of interventions to maximize quality-adjusted life years (QALYs), subject to varied budget and equity constraints. RESULTS: For no additional cost, approximately 211,000 QALYs can be gained over the lifetimes of all persons newly diagnosed with diabetes by implementing interventions rather than standard care. With increased availability of funds, additional health benefits can be gained but with diminishing marginal returns. The impact of equity constraints is extensive compared to the solution with the same intervention costs and no equity constraint. Under the conditions modeled, intensified hypertension control and smoking cessation interventions were provided most often, and intensive glycemic control and cholesterol reduction interventions were provided less often. CONCLUSIONS: A resource allocation model identifies trade-offs involved when imposing budget and equity constraints on care for individuals with newly diagnosed diabetes.

Adult↗
PubMedDate not supplied

Application of mathematical tools for metabolic design of microbial ethanol production.

Many attempts to engineer cellular metabolism have failed due to the complexity of cellular functions. Mathematical and computational methods are needed that can organize the available experimental information, and provide insight and guidance for successful metabolic engineering. Two such methods are reviewed here. Both methods employ a (log)linear kinetic model of metabolism that is constructed based on enzyme kinetics characteristics. The first method allows the description of the dynamic responses of metabolic systems subject to spatiotemporal variations in their parameters. The second method considers the product-oriented, constrained optimization of metabolic reaction networks using mixed-integer linear programming methods. The optimization framework is used in order to identify the combinations of the metabolic characteristics of the glycolytic enzymes from yeast and bacteria that will maximize ethanol production. The methods are also applied to the design of microbial ethanol production metabolism. The results of the calculations are in qualitative agreement with experimental data presented here. Experiments and calculations suggest that, in resting Escherichia coli cells, ethanol production and glucose uptake rates can be increased by 30% and 20%, respectively, by overexpression of a deregulated pyruvate kinase, while increase in phosphofructokinase expression levels has no effect on ethanol production and glucose uptake rates.

Bacteriological Techniques↗
PubMed2000

Metabolism of citric acid production by Aspergillus niger: model definition, steady-state analysis and constrained optimization of citric acid production rate.

In an attempt to provide a rational basis for the optimization of citric acid production by A. niger, we developed a mathematical model of the metabolism of this filamentous fungus when in conditions of citric acid accumulation. The present model is based in a previous one, but extended with the inclusion of new metabolic processes and updated with currently available kinetic data. Among the different alternatives to represent the system behavior we have chosen the S-system representation within power-law formalism. This type of representation allows us to verify not only the ability of the model to exhibit a stable steady state of the integrated system but also the robustness and quality of the representation. The model analysis is shown to be self-consistent, with a stable steady state, and in good agreement with experimental evidence. Moreover, the model representation is sufficiently robust, as indicated by sensitivity and steady-state and dynamic analyses. From the steady-state results we concluded that the range of accuracy of the S-system representation is wide enough to model realistic deviations from the nominal steady state. The dynamic analysis indicated a reasonable response time, which provided further indication that the model is adequate. The extensive assessment of the reliability and quality of the model put us in a position to address questions of optimization of the system with respect to increased citrate production. We carried out the constrained optimization of A. niger metabolism with the goal of predicting an enzyme activity profile yielding the maximum rate of citrate production, while, at the same time, keeping all enzyme activities within predetermined, physiologically acceptable ranges. The optimization is based on a method described and tested elsewhere that utilizes the fact that the S-system representation of a metabolic system becomes linear at steady state, which allows application of linear programming techniques. Our results show that: (i) while the present profile of enzyme activities in A. niger at idiophase steady state yields high rates of citric acid production, it still leaves room for changes and suggests possible optimization of the activity profile to over five times the basal rate synthesis; (ii) when the total enzyme concentration is allowed to double its basal value, the citric acid production rate can be increased by more than 12-fold, and even larger values can be attained if the total enzyme concentration is allowed to increase even more (up to 50-fold when the total enzyme concentration may rise up to 10-fold the basal value); and (iii) the systematic search of the best combination of subsets of enzymes shows that, under all conditions assayed, a minimum of 13 enzymes need be modified if significant increases in citric acid are to be obtained. This implies that improvements by single enzyme modulation are unlikely, which is in agreement with the findings of some investigators in this and other fields.

Aspergillus niger↗
PubMed2003

Modeling of yeast metabolism and process dynamics in batch fermentation.

Much is known about yeast metabolism and the kinetics of industrial batch fermentation processes. In this study, however, we provide the first tool to evaluate the dynamic interaction that exists between them. A stoichiometric model, using wine fermentation as a case study, was constructed to simulate batch cultures of Saccharomyces cerevisiae. Five differential equations describe the evolution of the main metabolites and biomass in the fermentation tank, while a set of underdetermined linear algebraic equations models the pseudo-steady-state microbial metabolism. Specific links between process variables and the reaction rates of metabolic pathways represent microorganism adaptation to environmental changes in the culture. Adaptation requirements to changes in the environment, optimal growth, and homeostasis were set as the physiological objectives. A linear programming routine was used to define optimal metabolic mass flux distribution at each instant throughout the process. The kinetics of the process arise from the dynamic interaction between the environment and metabolic flux distribution. The model assessed the effect of nitrogen starvation and ethanol toxicity in wine fermentation and it was able to simulate fermentation profiles qualitatively, while experimental fermentation yields were reproduced successfully as well.

Adaptation, Physiological↗
PubMed2003

Data reconciliation and parameter estimation in flux-balance analysis.

Flux blance analysis (FBA) has been shown to be a very effective tool to interpret and predict the metabolism of various microorganisms when the set of available measurements is not sufficient to determine the fluxes within the cell. In this methodology, an underdetermined stoichiometric model is solved using a linear programming (LP) approach. The predictions of FBA models can be improved if noisy measurements are checked for consistency, and these in turn are used to estimate model parameters. In this work, a formal methodology for data reconciliation and parameter estimation with underdetermined stoichiometric models is developed and assessed. The procedure is formulated as a nonlinear optimization problem, where the LP is transformed into a set of nonlinear constraints. However, some of these constraints violate standard regularity conditions, making the direct numerical solution very difficult. Hence, a barrier formulation is used to represent these constraints, and an iterative procedure is defined that allows solving the problem to the desired degree of convergence. This methodology is assessed using a stoichiometric yeast model. The procedure is used for data reconciliation where more reliable estimations of noisy measurements are computed. On the other hand, assuming unknown biomass composition, the procedure is applied for simultaneous data reconciliation and biomass composition estimation. In both cases it is verified that the f measurements required to get unbiased and reliable estimations is reduced if the LP approach is included as additional constraints in the optimization.

Acetates↗
PubMed2003

Theoretical and computational studies of the glucose signaling pathways in yeast using global gene expression data.

We have combined DNA microarray experiments with novel computational methods as a means of defining the topology of a biological signal transduction pathway. By DNA microarray techniques, we previously acquired data on expression over time of all genes in the yeast Saccharomyces following addition of glucose to wild-type cells and to cells mutated in one or more components of the Ras signaling network. In addition, we examined the time course of expression following activation of components of the Ras signaling network in the absence of glucose addition. In this current study, we have applied a novel theoretical and computational framework to these data to identify the network topology of the glucose signaling pathway in yeast and the role of Ras components in that network. The computational approach involves clustering genes by expression pattern, postulating a signaling network topology superstructure that includes all possible component interconnections and then evaluating the feasibility of the superstructure interconnections by optimization methods using Mixed Integer Linear Programming techniques. This approach is the first rigorous mathematical framework for addressing the biological network topology issue, and the novel formulation features the introduction of discrete variables for the connectivity and logical expressions that connect the experimental observations to the network structure. This analysis yields a topology for the glucose signaling pathway that is consistent with, and an extension of, known biological interactions in glucose signaling.

Computer Simulation↗
PubMed2003

Prediction of beta-sheet topology and disulfide bridges in polypeptides.

An ab initio method has been developed to predict beta architectures in polypeptides. The approach predicts the topology of beta-sheets and disulfide bridges through a novel superstructure-based mathematical framework originally established for chemical process synthesis problems. Two types of superstructure are introduced, both of which emanate from the principle that hydrophobic interactions drive the formation of a beta-structure. The mathematical formulation of the problem results in a set of integer linear programming (ILP) problems that can be solved to global optimality to identify the optimal beta-configuration. These (ILP) models can also predict a ranked ordered list of the best, second-best, third-best, etc., topologies of beta-sheets and disulfide bridges. The approach is shown to perform very well for several benchmark polypeptide systems, as well as polypeptides exhibiting challenging nonsequential beta-sheet topologies folds (56 to 187 amino acids).

Algorithms↗
PubMed1977

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Administration, Oral↗
PubMed1995

A novel skeletal drug delivery system using self-setting calcium phosphate cement. 9: Effects of the mixing solution volume on anticancer drug release from homogeneous drug-loaded cement.

The effects of mixing solution volume (0.25-0.65 mL/g) on in vitro drug release from a self-setting bioactive calcium phosphate cement containing the anticancer agent 6-mercaptopurine (6-MP) as a model compound were investigated. The drug release profiles from isolated planar surfaces as well as the entire surfaces of cement systems containing 5% 6-MP were measured in simulated body fluid at pH 7.25 and 37.0 degrees C. The drug release rate from both cement system geometries increased with increasing mixing solution volume. Drug release profiles from the planar-release and entire-surface-release cement matrix systems were analyzed by and found to agree with the Higuchi and Cobby equations, and the kinetic parameters were estimated with a nonlinear least-squares computer program. Linear relationships were found between the mixing solution volume and the drug release rate constants or time required for 50% drug release for both cement release geometries. Furthermore, the total pore volume of the cements, as measured by mercury porosimetry, increased with increasing mixing solution volume.

Antineoplastic Agents↗