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PubMed1986

A discrete model of bacterial metabolism.

This paper describes a computer model of the intermediary metabolism of bacteria during steady-state growth and during adaptations, e.g. to new carbon sources. Metabolic regulation is represented as a process of optimisation, in which the trend is towards improved metabolic performance. The model uses linear programming techniques for the optimisation. The implementation falls into four phases: (i) assembly of model parameters; (ii) calculations; (iii) storage of solutions and (iv) projection of solutions. The use of a commercial database and a commercial spreadsheet has proved to be of great assistance in the first and third phases. A metabolic map format, with the optional addition of conversion values, names of enzymes or co-factors has been used to project the results in a form convenient for inspection.

Algorithms↗
PubMed1992

Using fragment lengths from incomplete digestion by multiply cleaving enzymes to map antibody binding sites on a protein.

The problem of mapping the positions of the unique binding sites of several monoclonal antibodies on a linear protein structure is considered. Data giving the incidence of binding of individual antibodies to fragments of the protein obtained from it by the incomplete chemical or enzymatic digestion are used to formulate a series of linear programming problems. The solution to these problems shows which orderings of binding sites are possible, and gives upper and lower bounds for the relative positions of the sites.

Algorithms↗
PubMed2026

Detecting and reconstructing breakage-fusion-bridge cycles from long-read sequencing using BFBArchitect.

MOTIVATION: Focal oncogene amplification is a key driver of tumor progression. Remarkably, the increased pathology depends on the context-whether the amplification is extrachromosomal (ecDNA) or intrachromosomal. EcDNA amplifications promote heterogeneity, therapy resistance, and poor prognosis. Focal intrachromosomal amplifications often arise through breakage-fusion-bridge (BFB) cycles, which produce highly rearranged but stable chromosomes. Distinguishing BFB from ecDNA remains challenging due to overlapping genomic signatures. To address this, we present BFBArchitect, a computational method leveraging long-read Oxford Nanopore data to identify BFB sequences consistent with both copy number and structural variations. RESULTS: We provide a novel combinatorial characterization of BFB, which naturally leads to an integer linear programming (ILP) optimization. The ILP optimization generates a BFB sequence that best explains experimentally observed copy numbers and foldback structural variants. We implement this idea in a tool called BFBArchitect, which achieves near-perfect accuracy in distinguishing BFB from non-BFB structures in extensive simulations as well as on 18 validated tumor samples. Moreover, it generates sequence-level BFB reconstructions that provide mechanistic insights into BFB formation, including repair mechanisms with template switching and other structural variants, and recapture of telomere for stabilization. AVAILABILITY AND IMPLEMENTATION: BFBArchitect is available at https://github.com/AmpliconSuite/BFBArchitect.

Sequence Analysis, DNA↗
PubMed1978

A simple method for the computation of first neighbour frequencies of DNAs from CD spectra.

A procedure for the computation of the first neighbour frequencies of DNA's is presented. This procedure is based on the first neighbour approximation of Gray and Tinoco. We show that the knowledge of all the ten elementary CD signals attached to the ten double stranded first neighbour configurations is not necessary. One can obtain the ten frequencies of an unknown DNA with the use of eight elementary CD signals corresponding to eight linearly independent polymer sequences. These signals can be extracted very simply from any eight or more CD spectra of double stranded DNA's of known frequencies. The ten frequencies of a DNA are obtained by least square fit of its CD spectrum with these elementary signals. One advantage of this procedure is that it does not necessitate linear programming, it can be used with CD data digitalized using a large number of wavelengths, thus permitting an accurate resolution of the CD spectra. Under favorable case, the ten frequencies of a DNA (not used as input data) can be determined with an average absolute error < 2%. We have also observed that certain satellite DNA's, those of Drosophila virilis and Callinectes sapidus have CD spectra compatible with those of DNA's of quasi random sequence; these satellite DNA's should adopt also the B-form in solution.

Animals↗
PubMed1989

Evaluating managerial efficiency of Veterans Administration medical centers using Data Envelopment Analysis.

This study applied the methodology of Data Envelopment Analysis (DEA) to the set of VA medical centers to evaluate their relative managerial efficiencies. Each VAMC was viewed as a producer of multiple outputs and a consumer of multiple inputs. DEA uses linear programming to identify resources that were underutilized and services that were inefficiently produced. Managerial strategies based on the dual variables were constructed to indicate the manner in which inefficient VAMCs may be made efficient. The analysis showed that relative inefficiency existed in about one third of the VAMCs nationwide. Elimination of this inefficiency would save the VA over $300 million annually on personnel, equipment, drugs, and supplies, without reducing the level of services provided. A subsequent analysis of co-variance revealed that VAMCs affiliated with a university were generally less efficient than those without such an affiliation. A similar finding was obtained for larger VAMCs relative to smaller medical centers. In neither case, however, should these results be construed to imply that VAMCs should terminate their university affiliations or that VAMCs should be made smaller since factors other than relative efficiency are clearly as or more important in such decisions.

Cost Control↗
PubMed1992

A weighting method for predicting protein structural class from amino acid composition.

A protein is generally classified into one of the following four structural classes: all alpha, all beta, alpha+beta and alpha/beta. In this paper, based on the weighting to the 20 constituent amino acids, a new method is proposed for predicting the structural class of a protein according to its amino acid composition. The 20 weighting parameters, which reflect the different properties of the 20 constituent amino acids, have been obtained from a training set of proteins through the linear-programming approach. The rate of correct prediction for a training set of proteins by means of the new method was 100%, whereas the highest rate of previous methods was 82.8%. Furthermore, the results showed that the more numerous training proteins, the more effective the new method.

Amino Acids↗
PubMedDate not supplied

Optimized dynamic rotation with wedges.

Dynamic rotation is a computer-controlled therapy technique utilizing an automated multileaf collimator in which the radiation beam shape changes dynamically as the treatment machine rotates about the patient so that at each instant the beam shape matches the projected shape of the target volume. In simple dynamic rotation, the dose rate remains constant during rotation. For optimized dynamic rotation, the dose rate is varied as a function of gantry angle. Optimum dose rate at each gantry angle is computed by linear programming. Wedges can be included in the optimized dynamic rotation therapy by using additional rotations. Simple and optimized dynamic rotation treatment plans, with and without wedges, for a pancreatic tumor have been compared using optimization cost function values, normal tissue complication probabilities, and positive difference statistic values. For planning purposes, a continuous rotation is approximated by static beams at a number of gantry angles equally spaced about the patient. In theory, the quality of optimized treatment planning solutions should improve as the number of static beams increases. The addition of wedges should further improve dose distributions. For the case studied, no significant improvements were seen for more than 36 beam angles. Open and wedged optimized dynamic rotations were better than simple dynamic rotation, but wedged optimized dynamic rotation showed no definitive improvement over open beam optimized dynamic rotation.

Humans↗
PubMed1979

Experience of the metabolisable energy system.

Advisory experience concerning the metabolisable energy standards for cattle and sheep introduced in 1976 is reviewed. The change appears to have proceeded smoothly, the new terminology and units being mastered and then used in discussions on dairy cow feeding. The system proposed has thrown new light on some old problems and also on established methods of feeding dairy cattle. "Feeding according to yield" and "lead feeding" need to be reinterpreted in the light of the probable dry matter intakes and live-weight changes of cows in early lactation. These parameters also affect the calculated levels of protein received in dairy compound feeds in early lactation. Group feeding of cows by stage of lactation, level of milk yield and live-weight change is readily accepted by managers of the larger dairy herds. Confidence in the accuracy of the dairy ME system has been built up, and its application to suckler cows has also proved successful. The variable net energy system for growing cattle enables ration formulation to be accomplished speedily and linear programming if desired. Published experiments have been used to confirm the accuracy of predicted live-weight gains when compared with observed gains. No sex effects are included in the system, although differences of +/- 10 per cent have been recorded in natural or hormone induced sex effect trials. The requirements for pregnant ewes have been shown to be too low and liable to reduce lamb birth-weights. In the case of growing lambs, a review of published experiments has shown that lambs grew faster than predicted, suggesting that the energy allowances are too high.

Animal Feed↗
PubMed1976

Shaping of isodose curves in intracavitary irradiation using the afterloading method. A feasibility study involving mathematical simulation.

The possibility of adjusting the irradiation scheme to shape the isodose curve around an intracavitary source arrangement was studied mathematically. The total number of millicurie hours of irradiation for each source position was derived by a linear programming approach, taking into account the shape of the tumor in three different cases. The practical isodose curves obtainable with the source arrangement chosen were compared with the shape desired.

Humans↗
PubMed1979

Information content of the multibreath nitrogen washout.

The distribution of ventilation per unit volume (Va/Vol) in the lung is often studied using the multibreath N2 washout test. Most approaches have focused on the determination of a single Va/Vol distribution (consisting of from two compartments to a continuum) compatible with the data, but because the potential number of lung units greatly exceeds the number of breaths measured, many distributions are usually compatible with a given set of washout data. Interpretation of single distributions therefore requires evaluation of the variability among all such compatible distributions. The technique of linear programing is well suited to evaluation of these compatible distributions and its application to the N2 washout is explained. Twelve examples of washout data are analyzed in this way. The results indicate that using the first 20 or so breaths of the washout, narrow distributions of Va/Vol are well specified. Distributions with up to four distinct modes are also well specified, but for broad distributions the shape cannot be adequately defined. Good resolution in the region of high Va/Vol is found to be critically dependent on measuring the first few breaths of the washout.

Computers↗
PubMed1990

Feed intake, weaning weight and net returns comparisons for four breeding systems.

Feed intake, weaning weight and direct and maternal contributions to weaning weight were estimated for four breeding systems using data collected between 1979 and 1986 from 773 cow-calf pairs at the Elora Beef Research Centre. Breeding systems included purebred Hereford (HE), small rotational dual purpose (SR) (a four-way rotational crossing system utilizing Tarentaise, Angus, Gelbvieh and Pinzgauer breeds), large rotational beef (LR) (composed of Maine-Anjou, Simmental and Charolais) and Angus-sired large rotational beef (AL) utilizing Angus as the sire breed and LR as the maternal breed. Large rotational dams had the highest feed intakes for both dry (8.9 kg DM/d) and lactation (11.5 kg DM/d) periods. Conversely, HE calves consumed the greatest amounts of creep feed (309 kg DM), followed by AL, SR and LR. The large rotational system had the highest weaning weights (265 kg) and direct (12.3 kg greater than average of observations) and maternal (9.6 kg greater than average of observations) contributions to weaning weight, followed by AL, SR and HE for all three traits. An equation was derived for net returns that included parameters for feed intake and direct and maternal weaning weight. A linear programming model was designed to incorporate this equation as the objective function and determine the breeding system(s) that maximized net returns under various production conditions. In general, LR produced the greatest net returns, followed by SR and either AL or HE, depending on specific resource constraints (limited feed supply or herd size) included in the model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Influence of variations in biological and economical parameters on beef production net returns.

Net returns were defined as a function of the monetary returns (revenue) generated by the outputs less the monetary costs generated by the variable inputs. Outputs included total weaning weights of steers and heifers, weight of cull cows and weight of open heifers. Inputs included both feed and nonfeed costs. The net returns equation was incorporated as the objective function in a linear programming model. By maximizing the objective function, the breeding system that generated the highest net returns could be identified considering certain resource constraints. Breeding systems included purebred Herefords; small rotational dual purpose (SR), utilizing the breeds Angus, Pinzgauer, Gelbvieh and Tarentaise; large rotational (LR), a three-way rotational cross with the breeds Charolais, Simmental and Maine-Anjou; and Angus-sired terminal (AL) utilizing Angus as the sire breed and LR heifers as the maternal breed. Large rotational generally produced the greatest net returns, followed by SR and either AL or HE, depending on specific resource constraints (limited feed supply or herd size), calving rates, management systems, environment, beef to feed price ratios and purchased or farm-produced (inexpensive) feed utilized. Only under the conditions of a herd size constraint and farm-produced feed did AL exceed SR in net returns. Hereford had larger net returns than LR only when the two breeding systems were evaluated in an environment assumed to be reproductively stressful to LR. Ranking of breeding systems were dependent on specific conditions and indicated that one must consider each resource constraint and environment in which cattle are expected to produce before making breeding system recommendations.

Animal Feed↗
PubMed1991

A Markovian decision model for beef cattle replacement that considers spring and fall calving.

In certain production environments, beef cows are mated during a breeding season that starts in early summer. Cows found not to be pregnant at the end of the breeding season could either be culled or retained and remated the following summer. Alternatively, nonpregnant cows could be mated in the winter. This option would result in having both a spring and a fall calving herd. The purpose of our study was to determine the optimal replacement policy (maximizing long-run average net returns) for a specific production environment by determining for each age of cow, reproductive status (nonpregnant or pregnant), and season of pregnancy checking (spring or fall) whether the cow should be retained to the next breeding season (summer or winter) or be replaced by a pregnant heifer. The problem was formulated as a Markovian decision process and the optimal policy was found by linear programming. The optimal policy was one in which nonpregnant cows were always culled and replaced by heifers in the summer breeding herd, resulting in spring calving only.

Animals↗
PubMed1975

Rumen modeling: rumen input-output balance models.

Two models of rumen fermentative relationships expressed as systems of simultaneous linear equations and based on requirements for maintenance of balances of elementary imput and output and metabolic pathways are presented in matrix format consistent with solution by linear programs. Matrix entries defining the two models were verified carefully based upon a survey of the literature, and conceptual bases of the models were validated by comparisons of model outputs with experimental data not used in model construction. The models then were used to evaluate interactions among feed composition, volatile fatty acid yields and patterns, microbial growth yields and efficiencies, and microbial metabolic pathways.

Amino Acids↗
PubMed1990

Formulation, nutritive value and sensory evaluation of a new weaning food based on sweet corn (Nutrimaiz) dehydrated pulp.

The objective of the present work was to develop a formulation for complementary infant and child feeding employing linear programing as a mathematical model for optimization. High lysine/high tryptophan sweet corn pulp in the dehydrated form was used as the main ingredient. The restrictions imposed on the model were nutrient requirements, adequate protein/energy ratio and minimum cost. The formula derived by the computer (FC) matched the amino acid requirements, the protein/energy ratio (NDPCal%) and was rated high in laboratory tests in terms of sensory qualities. The cost determined for this formula was competitive in relation to commercial products used for the same purpose. Formula A, which contained 5% more sweet corn pulp and 10% less whole powdered milk, did not differ in nutritional, sensorial and functional properties from the formula FC and was chosen for the field acceptability trial because of its lower cost. Formula A had protein efficiency ratio and Biological Value similar to casein for the rat but protein digestibility and net protein utilization were statistically lower (p less than 0.05) for formula A than for casein. Acceptability tested on children who were 8-18 months of age ranged from 80-90%, average value 87%.

Amino Acids↗
PubMed1989

Indirect calorimetry evaluation of dietary protein and animal fat effects on energy utilization of laying hens.

A multichamber indirect calorimeter was constructed and used to measure energy utilization of laying hens. Four basic diets were formulated by a least cost linear program for use in this study. The first diet was formulated to meet the 1984 National Research Council (NRC) recommendations and contained by analysis 14.5% protein, .58% TSAA, and .68% lysine (designated NRC). The second diet (NRCAA) was formulated to the same amino acid specifications without a protein restriction and contained 12.9% protein, .57% TSAA, and .69% lysine. Another pair of diets was formulated with higher protein (HP) and amino acid restrictions. The HP diet contained 16% protein, .67% TSAA, and .85% lysine; whereas the HPAA diet had 14% protein, .68% TSAA, and .86% lysine. Four additional diets were formulated with the inclusion of 3% animal fat, using the same protein and amino acid restrictions as were used to formulate the first four diets. Animal fat supplementation significantly (P less than .05) improved energy balance (retention) of birds fed all formulations compared with the diets without added fat. Formulation of a diet based on amino acid restrictions significantly increased net energetic efficiency of birds fed amino acid levels higher than those recommended by the NRC (79.2 for HPAA vs. 62.1% for HP), but did not significantly affect net efficiency of birds fed the lower amino acid levels (NRC and NRCAA).

Animal Feed↗
PubMed1976

Adrenodoxin reductase-adrenodexin complex.

Adrenodoxin reductase and adrenodoxin have been shown (Chu, J.-W., and Kimura, T. (1973) J. Biol. Chem. 248, 5183-5187) to form a low dissociation constant, 1:1 complex when both proteins are in the oxidized form. We have found that when adrenodoxin: adrenodoxin reductase ratios are varied by increasing the adrenodoxin concentration, with adrenodoxin reductase held constant, an increasing rate of cytochrome c reduction, with NADPH as reductant, is seen up to a ratio of 1:1, indicating that cytochrome c reduction occurs via the protein-protein complex. Spectra observed during titration of this protein-protein complex with NADH were resolved into components by the linear programming method, using a computer program written in Fortran IV. Analysis of the data has shown that the flavoprotein is reduced prior to the iron sulfur protein, and that the midpoint oxidation-reduction potentials (pH 7.5) of the two proteins are -295 and -331 mV, respectively, when both are present in the complex. Complex formation does not alter the potential of adrenodoxin reductase, but changes that of adrenodoxin by -40 mV. Equilibrium constants derived from potential measurements show that the strength of the protein-protein interaction in the complex is unaltered by reduction of adrenodoxin reductase, but is decreased by about 1 kcal due to reduction of adrenodoxin. The low dissociation constants for both oxidized reduced forms of the adrenodoxin reductase-adrenodoxin complex indicate that the complex must remain associated throughout its catalytic cycle. Titration of the adrenodoxin reductase-adrenodoxin complex with the physiologic reductant, NADPH, was followed by EPR and visible spectra, and yielded an order of reduction of the components identical with that seen when NADH was used as reductant. Reduction of the protein-protein complex with NADPH yielded a ternary complex between NADP+, flavoprotein, and iron sulfur protein, with the two electrons located in a "charge transfer" complex between flavoprotein and pyridine nucleotide.

Adrenal Cortex↗
PubMed1990

[The optimization of the dosimetric plan in the intracavity radiotherapy of patients with cancer of the corpus uteri].

The potentialities of mathematical optimization were investigated with respect to dosimetric design of radiation therapy of endometrial cancer patients using AGAT-V and AGAT-VU [correction of Agat-B and Agat-Y] apparatus. The effectiveness of linear programming for creating in a pathological focus and in normal tissues of a dose distribution, meeting clinical requirements to the maximum, was shown.

Brachytherapy↗