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PubMed1995

Interventional telemedicine for noninvasive neuroradiosurgery: remote-site high-performance computing, mathematical optimization, and virtual scenario simulation.

Interventional Telemedicine may have potential utility in providing connectivity and access to specialized high performance computing and advanced software resources in support of clinical procedures in the field of Minimally-Invasive Surgery and Stereotactic Linear Accelerator (LINAC) Radiosurgery. Such interventions may benefit from application of nonlinear quadratic inverse solution methods designed to provide the capability to reverse optimize a 'best case' treatment plan. The formidable decision-making challenges posed by increasingly complex optimized data and progressively versatile LINAC delivery systems require volume visualization of projected treatment data and imaging anatomy via photorealistic rendering and virtual scenario simulation techniques. Both these new directions are heavily dependent on access to specialized high performance computing platforms solely accessible via broad-bandwidth network connectivity. This pilot project presents resimulation of retrospective radiosurgical case data using inverse solution optimization models running on workstation clusters and then volume rendered and simulated on the Princeton Graphics Engine Supercomputer. Evidence for effective utilization of such optimization and virtual simulation methods running on remotely accessed, distant high performance computing resources is discussed in view of the potential for long-term clinical investigation and eventual development of Interventional Telemedicine as a clinically practical approach for providing support to remote or non-urban radiosurgery centers in the industrialized and developing world.

Algorithms↗

PubMed1991

Optimization of cultivation and nutrition conditions and substrate pretreatment for solid-substrate fermentation of wheat straw by Coriolus versicolor.

Bioconversion of wheat straw by solid-substrate fermentation (SSF) with Coriolus versicolor was optimized by varying its physiological parameters. Selective delignification (more lignin than holocellulose degradation) and increases in crude protein (CP) content and in vitro dry matter digestibility (IVDMD) were taken as the criteria to select optimum levels of these parameters. The fungus behaved optimally under the following set of cultural and nutritional conditions: pH 5.5, moisture level 55%, temperature 30 degrees C, duration of fermentation 21 d, form of inoculum--grain culture, turning frequency--once at mid-incubation, urea (nitrogen source) 1.5% (sterile) or 3.0% (nonsterile), single superphosphate (phosphorus + sulfur source) 1.0%, no addition of free polysaccharides (as whey or molasses). A maximum of 17.5% increase in IVDMD involving 4.3% degradation of lignin, was attained in the optimized SSF under laboratory conditions. The digestibility improvement could be further increased by using a substrate pretreatment (physical/chemical/biological) in the following order of preference: NaOH treatment, urea or urine treatment, ensiling, steaming, grinding. For practical farm applications, urea treatment and ensiling appeared most feasible. The laboratory optimized process was also scaled up to 4 kg (sterile and unsterile) and 50 kg (unsterile) fermentations.

Animal Feed↗

PubMed2004

Improved elastase production by Bacillus sp. EL31410--further optimization and kinetics studies of culture medium for batch fermentation.

An efficient culture medium producing a bacterial elastase with high yields was developed further following preliminary studies by means of response surface method. Central composite design (CCD) and response surface methodology were applied to optimize the medium constituents. A central composite design was used to explain the combined effect of three medium constituents, viz, glucose, K(2)HPO(4), MgSO(4).7H(2)O. The strain produced more elastase in the completely optimized medium, as compared with the partially optimized medium. The fitted model of the second model, as per RSM, showed that glucose was 7.4 g/100 ml, casein 1.13 g/100 ml, corn steep flour 0.616 g/100 ml, K(2)HPO(4) 0.206 g/100 ml and MgSO(4).7H(2)O 0.034 g/100 ml. The fermentation kinetics of these two culture media in the flask experiments were analyzed. It was found that the highest elastase productivity occurred at 54 hours. Higher glucose concentration had inhibitory effect on elastase production. At the same time, we observed that the glucose consumption rate was slow in the completely optimized medium, which can explain the lag period of the highest elastase production. Some metal ions and surfactant additives also affected elastase production and cell growth.

Bacillus↗

PubMed2004

Multiobjective optimization and multivariable control of the beer fermentation process with the use of evolutionary algorithms.

This paper describes empirical research on the model, optimization and supervisory control of beer fermentation. Conditions in the laboratory were made as similar as possible to brewery industry conditions. Since mathematical models that consider realistic industrial conditions were not available, a new mathematical model design involving industrial conditions was first developed. Batch fermentations are multiobjective dynamic processes that must be guided along optimal paths to obtain good results. The paper describes a direct way to apply a Pareto set approach with multiobjective evolutionary algorithms (MOEAs). Successful finding of optimal ways to drive these processes were reported. Once obtained, the mathematical fermentation model was used to optimize the fermentation process by using an intelligent control based on certain rules.

Algorithms↗

PubMed1976

Application of mathematical optimization methods in microbiology.

Mathematical methods of experiment design have so far found little use in the optimization of microbiological processes. The conventional optimization procedure is still the transformation of functional relationship of n variables into n unidimensional optimizations; furthermore, the Box-Wilson gradient method is often used. This paper presents a review of methods used in other fields, and their application in microbiological practice. The methods are classified according to whether they require, besides the simple determination of the objective function (direct search methods), also the finding of its first (gradient methods) or second derivative (Newton-Raphson method). A modified Rosenbrock's method of direct optimum search and the gradient Box-Wilson method were used in parallel for the optimization of yeast growth on methanol. Their comparison showed that Rosenbrock's method is more suitbale for multiparameter systems.

Candida↗

PubMed1991

Multivariable optimization of mechanical ventilation. A linear programming approach.

The proposed method aims at improved ventilatory care with reduced morbidity. It combines two important aspects of mechanical ventilation: gas exchange and lung mechanics. A single criterion was selected as optimization index of lung trauma: peak respiratory power (PRP) defined as the maximum product of pressure times flow during inspiration. Arterial blood gases reflect gas exchange and constitute the constraints of the problem. The constraints as well as the optimization index are expressed as linear functions of the input variables (frequency of breathing, tidal volume, and positive end expiratory pressure). A linear programming approach can therefore be used to determine the values of input variables that minimize PRP and at the same time keep arterial blood gases within the prescribed limits. The coefficients of the constraints and the optimization index equation are found by manipulating input variables in order to obtain four different values of PaO2, PaCO2 and PRP (there are four coefficients in each equation). The coefficients can then be calculated and the optimization procedure run. In a pilot study 5 patients suffering from diseases of varying pulmonary pathology were investigated with this method. In 4 out of 5 the ventilator treatment improved in terms of blood gas values (mean increase in PaO2 was 4.7%) and reduction of mechanical load on the lungs (mean PRP reduction was 20%). Lower PRP is accompanied by lower mean power and pressure values, which results in increased cardiac output. Presently, the main problem is the time it takes to determine the patient coefficients (approx one hour), a procedure that needs to be simplified.

Acute Disease↗

PubMed2000

Optimization study on the formulation of roxithromycin dispersible tablet using experimental design.

This study set out to improve the physical and pharmaceutical characteristics of the present formulation using an appropriate experimental design. The work described here concerns the formulation of the dispersible tablet applying direct compression method containing roxithromycin in the form of coated granules. In this study 2(3) factorial design was used as screening test model and Central Composite Design (CCC) associated with response surface methodology was used as optimization study model to develop and to optimize the proper formulation of roxithromycin dispersible tablet. The three independent variables investigated were functional excipients like binder (X1), disintegrant (X2) and lubricant (X3). The effects of these variables were investigated on the following responses: hardness (Y1), friability (Y2) and disintegration time (Y3) of tablet. Three replicates at the center levels of the each design were used to independently calculate the experimental error and to detect any curvature in the response surface. This enabled the best formulations to be selected objectively. The effect order of each term to all response variable was X3> X2> X1> X1*X2> X2*X2> X2*X3> X3*X3> X1*X3> X1*X1 and model equations on each response variables were generated. Optimized compositions of formula were accordingly computed using those model equations and confirmed by following demonstration study. As a result, this study has demonstrated the efficiency and effectiveness of using a systematic formulation optimization process to develop the tablet formulation of roxithromycin dispersible tablet with limited experiment.

Anti-Bacterial Agents↗

PubMed2004

Optimizing the novel formulation of liposome-polycation-DNA complexes (LPD) by central composite design.

LPD vectors are non-viral vehicles for gene delivery comprised of polycation-condensed plasmid DNA and liposomes. Here, we described a novel anionic LPD formulation containing protamine-DNA complexes and pH sensitive liposomes composed of DOPE and cholesteryl hemisuccinate (Chems). Central composite design (CCD) was employed to optimize stable LPD formulation with small particle size. A three factor, five-level CCD design was used for the optimization procedure, with the weight ratio of protamine/DNA (X1), the weight ratio of Chems/ DNA (X2) and the molar ratio of Chems/DOPE in the anionic liposomes (X3) as the independent variables. LPD size (Y1) and LPD protection efficiency against nuclease (Y2) were response variables. Zeta potential determination was utilized to define the experimental design region. Based on experimental design, responses for the 15 formulations were obtained. Mathematical equations and response surface plots were used to relate the dependent and independent variables. The mathematical model predicted optimized X1-X3 levels that achieve the desired particle size and the protection efficiency against nuclease. According to these levels, an optimized LPD formulation was prepared, resulting in a particle size of 185.3 nm and protection efficiency of 80.22%.

Cations↗

PubMed1996

Optimal dose of thiamylal in combination with midazolam for induction of anaesthesia.

PURPOSE: The optimal dose range of thiamylal, combined with midazolam, in the induction of anaesthesia was evaluated using haemodynamic variables. METHODS: The 200 patients, aged 30 to 70 yr, were randomly divided into five groups by midazolam dosage. Anaesthesia was induced with midazolam 0.05, 0.075, 0.10, 0.15, or 0.20 mg.kg-1. Two minutes later, 50 mg thiamylal was administered followed by 25 mg increments until verbal response and eyelash reflex disappeared and blood pressure decreased to a level less than that of preinduction. Tracheal intubation was performed with 0.15 mg.kg-1 vecuronium. Blood pressure and heart rate were monitored during induction. Optimal induction was defined as a systolic blood pressure one minute after intubation within +/- 20% of that before induction. RESULTS: There were 164 patients whose systolic blood pressure were within these criteria. Blood pressure decreased two minutes after induction and 3 to 15 min after intubation in all groups. Heart rate increased one minute after intubation in 0.05 mg.kg-1, 0.075 mg.kg-1 and 0.10 mg.kg-1 midazolam groups. The optimal range of thiamylal was 4.0 +/- 1.1 (mean + SD), 3.1 +/- 1.2, 2.8 +/- 1.1, 2.3 +/- 1.2, and 1.7 +/- 1.0 mg.kg-1 in combination with midazolam 0.05, 0.075, 0.10, 0.15, and 0.20 mg.kg-1, respectively. CONCLUSION: The optimal dose range, to maintain haemodynamic stability, for thiamylal induction of anaesthesia in combination with midazolam, 0.05-0.2 mg.kg-1 was found to range from 4.0 to 1.7 mg.kg-1.

Adult↗

PubMed2005

Evaluation of HDR interstitial breast implants planned by conventional and optimized CT-based dosimetry systems with respect to dose homogeneity and conformality.

BACKGROUND AND PURPOSE: Recently, the use of brachytherapy for partial breast irradiation has increased significantly. The aim of this study was to make dosimetric comparisons between conventional (CONV) and CT-based optimized dosimetry systems applied to breast implants. PATIENTS AND METHODS: 17 patients treated with high-dose-rate (HDR) interstitial brachytherapy were selected for the study. Two patients had two-plane and 15 three-plane implants. Treatment planning was based on conventional two isocentric radiographs and dose point optimization (CONV). For each patient postimplant CT scans were taken, and the target volume (lumpectomy cavity with 1 cm margin) was outlined in all axial slices. The treatment planning was repeated using CT images. The dose distributions were analyzed by dose-volume histograms. To quantify the dose distributions, volume (V90, V100, V150, V200) and dose (D90, D(min), mean central dose [MCD]) parameters, along with the dose nonuniformity ratio (DNR), dose homogeneity index (DHI), external volume index (EI) and conformal index (COIN) were used. For each implant, three more virtual treatment plans were created using the Paris dosimetry system (PDS), geometrically optimized system (GOS) and conformal system (CONF). Dose and volume parameters were calculated and compared. RESULTS: The median number of catheters amounted to ten (range: 6 to 13) and the average volume of planning target volume to 63.4 cm(3) (range: 17.7-122 cm(3)). The mean target coverage was 70%, 61%, 57% and 87%; the D90 72%, 64%, 60% and 94%; the DNR 0.35, 0.25, 0.25 and 0.55; the EI 0.62, 0.54, 0.08 and 0.15; the COIN 0.40, 0.34, 0.50 and 0.74 for the CONV, PDS, GOS and CONF systems, respectively. CONCLUSION: With CT-based optimized dose planning the target coverage can be significantly increased compared to the conventional dosimetry systems, but the target dose distribution will be more inhomogeneous. To improve the quality of brachytherapy implants, the image-based three-dimensional information should be used not only for dose plan evaluation, but also previously, for planning the geometry of the catheter positions and performing the insertions.

Brachytherapy↗

PubMed1994

[The optimal administration time for neostigmine following atracurium blockade. Kinetics of antagonists].

UNLABELLED: The aims of the study were: (1) to predict reversal time from intensive atracurium blockade; and (2) to determine the optimal time of neostigmine administration during recovery from atracurium blockade, i.e., the time at which the administration of neostigmine results in the shortest total recovery time (time from administration of last supplemental dose of atracurium to train-of-four [TOF] ratio 0.70), and at the same time results in the shortest time from administration of neostigmine to TOF ratio 0.70. METHOD: The spontaneous and neostigmine-facilitated recovery in 52 healthy women anaesthetised with thiopentone, fentanyl, droperidol, and nitrous oxide was followed. Post-tetanic count (PTC) of TOF stimulation of the ulnar nerve and mechanomyography were used for monitoring neuromuscular transmission. The neuromuscular blockade was induced with atracurium 0.6 mg/kg and supplemental doses of 0.15 mg/kg were given when the first twitch response in the TOF (TH1) had recovered to 20%. Neostigmine 0.036 mg/kg body weight was given at different levels of neuromuscular blockade to 37 of the patients. RESULTS: Multiple regression analyses including pre-reversal time (time from administration of the last atracurium dose to neostigmine administration), PTC, weight, and age of the patients suggest that pre-reversal time is the best predictor of reversal time: reversal time = 27.3 min - (0.89 x pre-reversal time [min]; (SEE = 6.0 min). If pre-reversal time is unknown, PTC can be used: reversal time = 24 min - (4.5 x ln PTC) at time of reversal); (SEE = 6.8 min). Total recovery time was 47 min (SEM = 2.0 min, n = 15) in the patients allowed to recover spontaneously, and 29 min (SEM = 1.2 min, n = 29) in the patients reversed by neostigmine; the difference of 18 min (SE diff 2.0 min) was significant (P < 0.0005). The level of blockade indicated by PTC (1-24) at the time of reversal had no influence on the total recovery time. The spontaneous recovery times from reappearance of TH1 and TH1 = 10% to TOF ratio 0.70 were 29.2 min (SEM = 1.7 min) and 24.4 min (SEM = 2.6 min), respectively. DISCUSSION: The results suggest that pre-reversal time is the strongest predictor of reversal time when neostigmine is administered during intense atracurium blockade. To achieve the optimal time-saving effect, neostigmine must be given 18 min (the time saved by giving neostigmine) plus 7 to 11 min (needed for neostigmine to reach its peak effect), giving a total of 25 to 29 min before TOF ratio 0.70. As TH1 is between 1% and 10% 25 to 29 min before TOF ratio 0.70 is reached during spontaneous recovery, the optimal level of neuromuscular blockade for neostigmine administration in atracurium blockade is when TH1 is between 1% and 10%. CONCLUSION: Reversal time can be predicted as 27.3 min - (0.89 x prereversal time (min), and the optimal time of neostigmine administration in atracurium blockade appears to be when TH1 is 1%-10%.

Adult↗

PubMed2004

Childhood adversities, parent-child relationships and dispositional optimism in adulthood.

BACKGROUND: Studies exploring the effects of childhood adversities and parent-child relationship on adulthood dispositional optimism are rather rare, have been performed on small, selected samples and lack analyses of interaction between childhood factors. METHOD: A total of 19970 working-aged Finns responded to the population-based HeSSup Study baseline questionnaire in 1998. The level of dispositional optimism (measured with the LOT-R scale) was analyzed according to self-reported childhood adversities, childhood parent-child relationships and their interaction, using multivariate linear regression analysis methods. A number of potential confounding factors (education, living alone, recent life events, somatic health and depressive mood) were taken into account. RESULTS: Childhood adversities were associated with decreasing optimism in a dose-response manner. Good parent-child relationships were associated with increasing optimism, with a partial buffering effect when confronting adversities. CONCLUSION: Those reporting childhood adversities and poor parent-child relationships had less optimistic expectations, which may need to be addressed in clinical settings.

Adult↗

PubMed2002

Serial measurements of energy expenditure in critically ill children: useful in optimizing nutritional therapy?

OBJECTIVES: To determine the variation in total daily energy expenditure (TDEE) and respiratory quotient (RQ) in mechanically ventilated children and examine the relation to daily and cumulative energy balance toward optimizing nutritional therapy. METHODS: Serial measurements of TDEE and RQ were performed in 18 patients (median age 16 months) with an indirect calorimeter during admission (total 69 TDEE measurements). Daily caloric intake was recorded, and after determination of the amount of carbohydrates and fat a RQ of these macronutrients (RQ(macr)) was obtained. Daily 24-h urine was analyzed for urinary nitrogen excretion. RESULTS: There was a great variability in the median serial TDEE between children (40-64 kcal/kg), while the variation within individual children was small; the mean intraindividual coefficient of variation (CV) in daily measurements of TDEE was less than 10% in 15 of the 18 children (83%). On the last day of measurement 8 children with a positive cumulative energy balance (+98 kcal/kg) had a significantly higher RQ than 10 with a negative cumulative energy balance (-24 kcal/kg, 0.89 vs. 0.84). From the difference between RQ and RQ(macr) the optimal caloric intake was determined as 1.4x TDEE, divided into 60% carbohydrates and 40% fat. From the median nitrogen excretion of 33 samples (300 mg/kg per day, range 60-708) optimal daily protein intake was calculated as 1.9 g/kg (range 0.4-4.4). CONCLUSIONS: For most children a single measurement of TDEE gave a good insight in the daily energy needs. RQ is strongly affected by the ratio energy intake/TDEE and by the cumulative energy balance. Optimal caloric intake was found to be 1.4x TDEE with a daily protein intake of 1.9 g/kg.

Child, Preschool↗

PubMed2004

Static pressure-volume curve characteristics are moderate estimators of optimal airway pressures in a mathematical model of (primary/pulmonary) acute respiratory distress syndrome.

OBJECTIVE: To study the value of objective pressure-volume characteristics for predicting optimal airway pressures and the development of atelectasis and overstretching during a structured lung volume recruitment procedure with subsequent reduction in airway pressures. METHODS: We used a mathematical model of a lung with adjustable characteristics of acute respiratory distress syndrome (ARDS) characteristics. Simulations were performed in five grades of ARDS in the presence of pure alveolar or combined alveolar-small airway closure as well complete or incomplete lung volume recruitability. For each simulation optimal end-expiratory pressure was determined. A static pressure-volume curve was constructed and objective characteristics of this curve calculated. The predictive value of these characteristics for end-expiratory atelectasis, overstretching, and optimal end-expiratory pressure was assessed. RESULTS: Simultaneous alveolar recruitment and overstretching during inflation were more pronounced than alveolar derecruitment and overstretching during deflation. End-expiratory pressure needed to prevent significant alveolar collapse in severe ARDS resulted in maximal safe tidal volumes that may be insufficient for adequate ventilation using conventional mechanical ventilatory modes. Plateau pressures well below the "upper corner point" (airway pressure where compliance decreases) resulted in significant alveolar overstretching. CONCLUSIONS: A recruitment maneuver followed by subsequent reduction in airway pressure limits end-expiratory atelectasis, overstretching, and pressure. None of the objective characteristics of the pressure-volume curve was predictive for end-expiratory atelectasis, overstretching, or optimal airway pressure.

Humans↗

PubMed1996

Activity of plasma membrane H+-ATPase and expression of PMA1 and PMA2 genes in Saccharomyces cerevisiae cells grown at optimal and low pH.

Cells of Saccharomyces cerevisiae grown in media with an initial pH of 2.5-6.0, acidified with a strong acid (HCl), exhibited the highest plasma membrane H+-ATPase-specific activity at an initial pH of 6.0. At a lower pH (above pH 2.5) ATPase activity (62-83% of the maximum level) still allowed optimal growth. At pH 2.5, ATPase activity was about 30% of the maximum value and growth was impaired. Quantitative immunoassays showed that the content of ATPase protein in the plasma membrane was similar across the entire pH range tested, although slightly lower at pH 2.5. The decrease of plasma membrane ATPase activity in cells grown at low pH was partially accounted for by its in vitro stability, which decreased sharply at pH below 5.5, although the reduction of activity was far below the values expected from in vitro measurements. Yeast growth under acid stress changed the pattern of gene expression observed at optimal pH. The level of mRNA from the essential plasma-membrane-ATPase-encoding gene PMA1 was reduced by 50% in cells grown at pH 2.5 as compared with cells grown at the optimal pH 5.0, although the content of ATPase in the plasma membrane was only modestly reduced. As observed in response to other kinds of stress, the PMA2 promoter at the optimal pH was up to eightfold more efficient in cells grown at pH 2.5, although it remained several hundred times less efficient than that of the PMA1 gene.

Cell Membrane↗

PubMed2001

Why are translationally sub-optimal synonymous codons used in Escherichia coli?

Natural selection favors certain synonymous codons which aid translation in Escherichia coli, yet codons not favored by translational selection persist. We use the frequency distributions of synonymous polymorphisms to test three hypotheses for the existence of translationally sub-optimal codons: (1) selection is a relatively weak force, so there is a balance between mutation, selection, and drift; (2) at some sites there is no selection on codon usage, so some synonymous sites are unaffected by translational selection; and (3) translationally sub-optimal codons are favored by alternative selection pressures at certain synonymous sites. We find that when all the data is considered, model 1 is supported and both models 2 and 3 are rejected as sole explanations for the existence of translationally sub-optimal codons. However, we find evidence in favor of both models 2 and 3 when the data is partitioned between groups of amino acids and between regions of the genes. Thus, all three mechanisms appear to contribute to the existence of translationally sub-optimal codons in E. coli.

Codon↗

PubMed1997

Optimization of environmental factors for the biological treatment of trinitrotoluene-contaminated soil.

In earlier studies (Boopathy et al. 1994a, 1994b), soil bacteria present in a TNT-contaminated site removed 2,4,6-trinitrotoluene (TNT). In this study the optimum conditions for the most efficient removal of TNT is discussed. The results suggest that the soil bacterial consortium has an optimal pH range of 6-7. Maximum growth was observed at pH 7. However, the TNT removal rate was higher at pH 6. Studies of the effects of temperature showed that the bacterial consortium had maximum metabolic activity at 20 to 22 degrees C (ambient temperature). At a higher temperature (37 degrees C) the TNT removal rate dropped significantly. The consortium could not use TNT as a nitrogen source but required the addition of ammonium. Optimal growth occurred with 0.25 g/L of ammonium chloride. Growing cells removed TNT significantly faster rates than resting cells or cell-free extract. The operation of soil slurry reactors with the optimal conditions suggested that TNT can be removed effectively from the contaminated sites. These environmental conditions established as optimal can be used to improve the efficiency of large-scale soil slurry reactors for the treatment of soil contaminated with TNT.

Biodegradation, Environmental↗

PubMed2001

Modelling and optimization of environmental conditions for kefiran production by Lactobacillus kefiranofaciens.

A mathematical model for kefiran production by Lactobacillus kefiranofaciens was established, in which the effects of pH, substrate and product on cell growth, exopolysaccharide formation and substrate assimilation were considered. The model gave a good representation both of the formation of exopolysaccharides (which are not only attached to cells but also released into the medium) and of the time courses of the production of galactose and glucose in the medium (which are produced and consumed by the cells). Since pH and both lactose and lactic acid concentrations differently affected production and growth activity, the model included the effects of pH and the concentrations of lactose and lactic acid. Based on the mathematical model, an optimal pH profile for the maximum production of kefiran in batch culture was obtained. In this study, a simplified optimization method was developed, in which the optimal pH profile was determined at a particular final fermentation time. This was based on the principle that, at a certain time, switching from the maximum specific growth rate to the critical one (which yields the maximum specific production rate) results in maximum production. Maximum kefiran production was obtained, which was 20% higher than that obtained in the constant-pH control fermentation. A genetic algorithm (GA) was also applied to obtain the optimal pH profile; and it was found that practically the same solution was obtained using the GA.

Algorithms↗