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An optimal operating strategy for fixed-bed bioreactors used in wastewater treatment.

Optimization of a fixed-bed bioreactor used in wastewater treatment is addressed. The objective of optimization is to maximize the treatment efficiency of the biofilter by manipulating the feed flow rate while satisfying operational constraints. Numerical results indicate that the optimal input is characterized as being on the boundary of the admissible region. Thus, the characterized optimal solution is implemented using a simple feedback control law, which provides the optimal input profile despite variations in substrate inlet concentration and biomass growth rate.

Biomass↗

Optimal covalent immobilization of glucose oxidase-containing liposomes for highly stable biocatalyst in bioreactor.

The glucose oxidase-containing liposomes (GOL) were prepared by entrapping glucose oxidase (GO) in the liposomes composed of phosphatidylcholine (PC), dimyristoyl L-alpha-phosphatidylethanolamine (DMPE), and cholesterol (Chol) and then covalently immobilized in the glutaraldehyde-activated chitosan gel beads. The immobilized GOL gel beads (IGOL) were characterized to obtain a highly stable biocatalyst applicable to bioreactor. At first, the glutaraldehyde concentration used in the gel beads activation as well as the immobilizing temperature and time were optimized to enhance the immobilization yield of the GOL to the highest extent. The liposome membrane composition and liposome size were then optimized to obtain the greatest possible immobilization yield of the GOL, the highest possible activity efficiency of the IGOL, and the lowest possible leakage of the entrapped GO during the GOL immobilization. As a result, the optimal immobilization conditions were found to be as follows: the liposome composition, PC/DMPE/Chol = 65/5/30 (molar percentage); the liposome size, 100 nm; the glutaraldehyde concentration, 2% (w/v); the immobilizing temperature, 4 degrees C; and the immobilizing time, 10 h. Furthermore, the optimal IGOL prepared were characterized by its rapidly increasing effective GO activity to the externally added substrate (glucose) with increasing temperature from 20 to 40 degrees C, and also by its high stability at 40 degrees C against not only the thermal denaturation in a long-term (7 days) incubation but also the bubbling stress in a bubble column. Finally, compared to the conventionally immobilized glucose oxidase (IGO), the higher operational stability of the optimal IGOL was verified by using it either repeatedly (4 times) or for a long time (7 days) to catalyze the glucose oxidation in a small-scale airlift bioreactor.

Adsorption↗

Application of artificial neural network coupling particle swarm optimization algorithm to biocatalytic production of GABA.

The biotransformation of L-sodium glutamate (L-MSG) to gamma-aminobutyric acid (GABA) catalyzed by the cells of Lactobacillus brevis with higher glutamate decarboxylase activity was investigated. The results showed that pH, temperature, and FeSO(4) x 7H(2)O concentration had significantly positive effect on GABA yield. The individual and interactive effects of pH, temperature, and FeSO(4) x 7H(2)O concentration were further optimized in terms of GABA yield. In the present work, an artificial neural network (ANN) and response surface methodology (RSM) models were developed, which incorporated pH, temperature, and FeSO(4) x 7H(2)O concentration as input variables, and GABA yield as output variable. The optimized ANN topology included four neurons in the hidden layer and the best network architecture was 3-4-1. The trained ANN gave total root-mean square error (sigma) equal to 1.84 for GABA yield while the RSM gave sigma equal to 2.63. The results demonstrated a slightly higher prediction accuracy of ANN compared to RSM. The modeled maximum GABA yield was identified by applying particle swarm optimization algorithm to the ANN model developed. The modeled maximum GABA yield reached 91 mM under the following optimal conditions: 25 mL Na(2)HPO(4)-citric acid buffer (100 mM, pH 4.23), 120 mM L-MSG, 0.83 g/L FeSO(4) x 7H(2)O, 10 microM PLP, the resting cells obtained from a 60-h culture broth, 2.68 g dry cell weight (DCW)/L, and without agitation at 40 degrees C for 5 h. The previous high value of GABA yield that was observed was 81.8 mM. The optimized conditions allowed GABA yield to be increased from 81.8 to 90.57 mM after verification experiments test.

Algorithms↗

Optimal deployment of third-generation stents: an intravascular ultrasound assessment.

Third-generation intracoronary stents allow deployment at higher pressures, possibly obviating the need for high-pressure postdilations and also possibly reducing restenosis. This study evaluated the ability of the Tristar Coronary Stent System to produce optimal stent deployment as measured by intravascular ultrasound (IVUS) and quantitative coronary angiography in 46 patients. Optimal stent deployment was defined as minimal luminal area > 80% of the average of the proximal and distal reference luminal areas. After initial deployment, 74.5% of stents met criteria for optimal stent deployment by IVUS, with an average stent expansion ratio of 89.6%. Ten stents (18.2%) were postdilated. Four patients (8.7%) had a major adverse cardiac event, one patient died, one patient had a myocardial infarction, and two patients had target vessel revascularization at 6 months. The Tristar stent system produces optimal deployment without the need for routine postdilation and results in optimal clinical outcomes.

Adult↗

Estimation of an optimal radiotherapy utilization rate for gynecologic carcinoma: part II--carcinoma of the endometrium.

BACKGROUND: Radiotherapy utilization rates for cancer vary widely, both within and between countries. Current estimates of the proportion of cancer patients who should optimally receive radiotherapy are based either on expert opinion or on the measurement of actual utilization rates, rather than on the best scientific evidence. METHODS: Evidence-based treatment guidelines regarding endometrial carcinoma were reviewed to develop an evidence-based benchmark for radiotherapy utilization. An optimal radiotherapy utilization tree was constructed and the proportions of endometrial carcinoma patients with clinical indications for radiotherapy were obtained from epidemiologic data. The ideal utilization rates were compared with actual radiotherapy utilization rates for endometrial carcinoma both in Australia and internationally. RESULTS: According to the best available evidence, radiotherapy is indicated at least once in 46% of all patients with endometrial carcinoma. A review of the limited data available concerning actual radiotherapy utilization rates revealed that the actual rates are approximately 10% lower than the optimal rates. CONCLUSIONS: Further research into the patterns of actual treatment and the development of optimal chemotherapy and surgery utilization rates for endometrial carcinoma is recommended. The difference between the optimal and the actual utilization rates warrants investigation into the reasons for the low radiotherapy utilization rates encountered in clinical practice.

Benchmarking↗

Optimization of the separation of a group of triazine herbicides by micellar capillary electrophoresis using experimental design and artificial neural networks.

The micellar electrokinetic chromatography separation of a group of triazine compounds was optimized using a combination of experimental design (ED) and artificial neural network (ANN). Different variables affecting separation were selected and used as input in the ANN. A chromatographic exponential function (CEF) combining resolution and separation time was used as output to obtain optimal separation conditions. An optimized buffer (19.3 mM sodium borate, 15.4 mM disodium hydrogen phosphate, 28.4 mM SDS, pH 9.45, and 7.5% 1-propanol) provides the best separation with regard to resolution and separation time. Besides, an analysis of variance (ANOVA) approach of the MEKC separation, using the same variables, was developed, and the best capability of the combination of ED-ANN for the optimization of the analytical methodology was demonstrated by comparing the results obtained from both approaches. In order to validate the proposed method, the different analytical parameters as repeatability and day-to-day precision were calculated. Finally, the optimized method was applied to the determination of these compounds in spiked and nonspiked ground water samples.

Chromatography, Micellar Electrokinetic Capillary↗

Optimal sampling theory: effect of error in a nominal parameter value on bias and precision of parameter estimation.

The authors examined the robustness of optimal sampling theory in estimating the parameter values of two different populations of patients receiving a constant rate, half-hour intravenous infusion of theophylline. One population consisted of smokers; the other included nonsmokers. The smoking population was predicted to have a serum clearance approximately 50% greater than the nonsmokers because of an induction of the cytochrome P450 system. After an initial study to provide both patient-specific and population mean parameter values, optimal sampling strategies that were derived from each population (seven sample split designs) and the patient's seven sample and four sample design were determined. A second study was performed with an overall sampling strategy that was superset of all the above strategies. The analysis of all samples served as the reference for the parameter values. Bias and precision of the values determined with each of the optimal sampling sets (seven sample sets based on the "correct" and "wrong" populations, the patient's seven and four sample sets) were determined relative to these reference values. Irrespective of the sample set used for analysis, unbiased and precise parameter estimates, particularly of hybrid parameters were provided. With the patient's four sample set, Vss was significantly biased, but the value of (2.2%) was clinically insignificant. The authors conclude that optimal sampling theory, as implemented in this study, provides robust estimates of important pharmacokinetic parameter values, even when errors of 50% are present in the clearance of the population used to calculate the optimal sampling design.

Adolescent↗

A MCSCF method for ground and excited states based on full optimizations of successive Jacobi rotations.

A new multiconfigurational self-consistent field (MCSCF) method based on successive optimizations of Jacobi rotation angles is presented. For given one- and two-particle density matrices and an initial set of corresponding integrals, a technique is developed for the determination of a Jacobi angle for the mixing of two orbitals, such that the exact energy, written as a function of the angle, is fully minimized. Determination of the energy-minimizing orbitals for given density matrices is accomplished by successive optimization and updating of Jacobi angles and integrals. The total MCSCF energy is minimized by alternating between CI and orbital optimization steps. Efficiency is realized by optimizing CI and orbital vectors quasi-simultaneously by not fully optimizing each in each improvement step. On the basis of the Jacobi-rotation based approach, a novel MCSCF procedure is formulated for excited states, which avoids certain shortcomings of traditional excited-state MCSCF methods. Applications to specific systems show the practicability of the developed methods.

Journal Article↗

A new program for optimizing periodic boundary models of solvated biomolecules (PBCAID).

Simulations of solvated macromolecules often use periodic lattices to account for long-range electrostatics and to approximate the surface effects of bulk solvent. The large percentage of solvent molecules in such models (compared to macromolecular atoms) makes these procedures computationally expensive. The cost can be reduced by using periodic cells containing an optimized number of solvent molecules (subject to a minimal distance between the solute and the periodic images). We introduce an easy-to-use program "PBCAID" to initialize and optimize a periodic lattice specified as one of several known space-filling polyhedra. PBCAID reduces the volume of the periodic cell by finding the solute rotation that yields the smallest periodic cell dimensions. The algorithm examines rotations by using only a subset of surface atoms to measure solute/image distances, and by optimizing the distance between the solute and the periodic cell surface. Once the cell dimension is optimized, PBCAID incorporates a procedure for solvating the domain with water by filling the cell with a water lattice derived from an ice structure scaled to the bulk density of water. Results show that PBCAID can optimize system volumes by 20 to 70% and lead to computational savings in the nonbonded computations from reduced solvent sizes. Copyright 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1843-1850, 2001

Journal Article↗

Geometry optimization in density functional methods.

The geometry optimization in delocalized internal coordinates is discussed within the framework of the density functional theory program deMon. A new algorithm for the selection of primitive coordinates according to their contribution to the nonredundant coordinate space is presented. With this new selection algorithm the excessive increase in computational time and the deterioration of the performance of the geometry optimization for floppy molecules and systems with high average coordination numbers is avoided. A new step selection based on the Cartesian geometry change is introduced. It combines the trust radius and line search method. The structure of the new geometry optimizer is described. The influence of the SCF convergence criteria and the grid accuracy on the geometry optimization are discussed. A performance analysis of the new geometry optimizer using different start Hessian matrices, basis sets and grid accuracies is given.

Journal Article↗

Component-based integration of chemistry and optimization software.

Typical scientific software designs make rigid assumptions regarding programming language and data structures, frustrating software interoperability and scientific collaboration. Component-based software engineering is an emerging approach to managing the increasing complexity of scientific software. Component technology facilitates code interoperability and reuse. Through the adoption of methodology and tools developed by the Common Component Architecture Forum, we have developed a component architecture for molecular structure optimization. Using the NWChem and Massively Parallel Quantum Chemistry packages, we have produced chemistry components that provide capacity for energy and energy derivative evaluation. We have constructed geometry optimization applications by integrating the Toolkit for Advanced Optimization, Portable Extensible Toolkit for Scientific Computation, and Global Arrays packages, which provide optimization and linear algebra capabilities. We present a brief overview of the component development process and a description of abstract interfaces for chemical optimizations. The components conforming to these abstract interfaces allow the construction of applications using different chemistry and mathematics packages interchangeably. Initial numerical results for the component software demonstrate good performance, and highlight potential research enabled by this platform.

Journal Article↗

Coupled atomic charge selectivity for optimal ligand-charge distributions at protein binding sites.

Charge optimization as a tool for both analyzing and enhancing binding electrostatics has become an attractive approach over the past few years. An interesting feature of this method for molecular design is that it provides not only the optimal charge magnitudes, but also the selectivity of a particular atomic center for its optimal charge. The current approach to compute the charge selectivity at a given atomic center of a ligand in a particular binding process is based on the binding-energy cost incurred upon the perturbation of the optimal charge distribution by a unit charge at the given atomic center, while keeping the other atomic partial charges at their optimal values. A limitation of this method is that it does not take into account the possible concerted changes in the other atomic charges that may incur a lower energetic cost than perturbing a single charge. Here, we describe a novel approach for characterizing charge selectivity in a concerted manner, taking into account the coupling between the ligand charge centers in the binding process. We apply this novel charge selectivity measure to the celecoxib molecule, a nonsteroidal anti-inflammatory agent binding to cyclooxygenase 2 (COX2), which has been recently shown to also exhibit cross-reactivity toward carbonic anhydrase II (CAII), to which it binds with nanomolar affinity. The uncoupled and coupled charge selectivity profiles over the atomic centers of the celecoxib ligand, binding independently to COX2 and CAII, are analyzed comparatively and rationalized with respect to available experimental data. Very different charge selectivity profiles are obtained for the uncoupled versus coupled selectivity calculations.

Binding Sites↗

Optimization and direct comparison of the dimerizer and reverse tet transcriptional control systems.

BACKGROUND: Exogenously controlled gene expression systems are essential for both the in vivo analysis of gene function and the regulated delivery of therapeutic gene products. However, differences in experimental methods used to characterize the various systems prohibit informative comparisons. The purpose of this study was to identify an optimal system for regulated gene expression studies through a rigorous direct comparison of the dimerizer and the reverse tet transactivator (rtTA) transcriptional switch systems. METHODS: An optimized bicistronic rapamycin-dependent dimerizer construct and an optimized rtTA construct (based on rtTA(s)-M2) were developed that utilize a chimeric mammalian activation domain with a flexible interdomain linker. These constructs were reconstituted in identical eukaryotic expression vectors and compared in transient transfection assays employing target gene reporter constructs that differ only in the relevant DNA binding sites. RESULTS: The optimized rtTA(s)-M2 construct, designated rtTAM2.2, exhibited a twofold increase in the magnitude of doxycycline-dependent reporter gene induction and an eightfold increase in sensitivity as compared to the rtTA(s)-M2 construct. This correlated with a significantly higher level of expression of the rtTAM2.2 protein. In direct comparisons the rtTAM2.2 system mediated inducible expression to a level tenfold greater than the bicistronic dimerizer system. However, while the dimerizer system exhibited no detectable rapamycin-independent expression, a low level of doxycycline-independent target gene expression was detectable. CONCLUSIONS: The improved rtTAM2.2 rtTA system described here may prove optimal when the overall magnitude of target gene induction is critical, while the dimerizer system may be advantageous when the complete absence of ligand-independent target gene expression is essential.

Animals↗

Can a single-shot black-blood T2-weighted spin-echo echo-planar imaging sequence with sensitivity encoding replace the respiratory-triggered turbo spin-echo sequence for the liver? An optimization and feasibility study.

PURPOSE: To optimize and assess the feasibility of a single-shot black-blood T2-weighted spin-echo echo-planar imaging (SSBB-EPI) sequence for MRI of the liver using sensitivity encoding (SENSE), and compare the results with those obtained with a T2-weighted turbo spin-echo (TSE) sequence. MATERIALS AND METHODS: Six volunteers and 16 patients were scanned at 1.5T (Philips Intera). In the volunteer study, we optimized the SSBB-EPI sequence by interactively changing the parameters (i.e., the resolution, echo time (TE), diffusion weighting with low b-values, and polarity of the phase-encoding gradient) with regard to distortion, suppression of the blood signal, and sensitivity to motion. The influence of each change was assessed. The optimized SSBB-EPI sequence was applied in patients (N = 16). A number of items, including the overall image quality (on a scale of 1-5), were used for graded evaluation. In addition, the signal-to-noise ratio (SNR) of the liver was calculated. Statistical analysis was carried out with the use of Wilcoxon's signed rank test for comparison of the SSBB-EPI and TSE sequences, with P = 0.05 considered the limit for significance. RESULTS: The SSBB-EPI sequence was improved by the following steps: 1) less frequency points than phase-encoding steps, 2) a b-factor of 20, and 3) a reversed polarity of the phase-encoding gradient. In patients, the mean overall image quality score for the optimized SSBB-EPI (3.5 (range: 1-4)) and TSE (3.6 (range: 3-4)), and the SNR of the liver on SSBB-EPI (mean +/- SD = 7.6 +/- 4.0) and TSE (8.9 +/- 4.6) were not significantly different (P > .05). CONCLUSION: Optimized SSBB-EPI with SENSE proved to be feasible in patients, and the overall image quality and SNR of the liver were comparable to those achieved with the standard respiratory-triggered T2-weighted TSE sequence.

Adenoma, Liver Cell↗

Optimized clinical T2 relaxometry with a standard CPMG sequence.

PURPOSE: To optimize the accuracy and precision of T2 measurements using the standard Carr-Purcell-Meiboom-Gill (CPMG) sequence. T2 values obtained with this technique are normally sensitive to imperfect refocusing due to the formation of unwanted stimulated echoes. MATERIALS AND METHODS: Modifications are made to the refocusing slice selection width and the interleaving scheme. A widened refocusing slice improves the uniformity of the refocusing flip angle across the slice. A slow spin echo acquisition provided "gold standard" T2 values. Repeated T2 measurements in phantom and human studies are used to compare the accuracy and precision of the optimized and non-optimized CPMG implementations. RESULTS: The required slice thickness ratio between refocusing and excitation slice widths is found to be 3:1 for typical optimized radiofrequency pulses. T2 values obtained using this optimized implementation more closely correspond to "gold standard" values. Repeated T2 measurements indicate significantly improved correspondence between data and model. A reduction in the fitting error of approximately 70% is demonstrated for phantoms. CONCLUSION: We demonstrate that a relatively simple change to the CPMG relaxometry sequence parameters from the default setup yields significant improvements in the accuracy and precision of T2 measurements.

Adult↗

Sequential parametric optimization of lipase production by a mutant strain Rhizopus sp. BTNT-2.

Lipase production by the mutant strain Rhizopus sp. BTNT-2 was optimized in submerged fermentation. Different chemical and physical parameters such as carbon sources, nitrogen sources, oils, inoculum level, pH, incubation time, incubation temperature and aeration have been extensively studied to increase lipase productivity. Potato starch (1.25% w/v) as a carbon source, corn steep liquor (1.5% w/v) as a nitrogen source and olive oil (0.5% v/v) as lipid source were found to be optimal for lipase production. The optimal levels of other parameters are 4 ml of inoculum (2.6x10(8) spores/ml), initial pH of 5.5, incubation time of 48 hours, incubation temperature of 28 degrees C and aeration rate of 120 rpm. With the optimized parameters, the highest production of lipase was 59.2 U/ml while an yield of only 28.7 U/ml was obtained before optimization resulting in 206% increase in the productivity.

Biomass↗

Optimization of a solid-phase microextraction procedure for the determination of herbicides by micellar electrokinetic chromatography.

The use of a different optimization procedure that involves Experimental Design (ED) and Artificial Neural Networks (ANN) for the off-line coupling solid-phase microextraction-micellar electokinetic chomatography (SPME-MEKC) is presented. This combination of ED and ANN, mathematical tools not previously used in SPME-MEKC optimization, allowed us to obtain good extraction efficiencies in the SPME procedure for the determination of a group of eleven triazine herbicides in groundwater samples. Both extraction and desorption steps were carried out by solution stirring at 900 rpm. Optimal conditions for the off-line SPME procedure were: extraction with a poly(dimethylsiloxane)/divinylbenzene SPME fiber for 120 min, 10% (w/v) NaCl, desorption time 40 min, and 70% (v/v) of methanol/buffer as desorption mixture. Detection limits lay between 0.80 microg L(-1) and 4.89 microg L(-1). Finally, the optimized method was applied to the determination of these compounds in spiked and non-spiked groundwater samples using a previously optimized MEKC separation.

Chromatography↗

Determination of an optimized conversion matrix for device independent skin color image analysis.

BACKGROUND AND OBJECTIVE: A cross-polarized diffuse reflectance (CDR) color imaging system was developed for quantitative evaluation of port wine stain (PWS) response to laser therapy. To obtain calibrated Commission International de l'Eclairage (CIE) color space images from RGB (red, green, and blue) images, it was necessary to derive an optimized conversion matrix specific to our imaging system. STUDY DESIGN/MATERIALS AND METHODS: A chromameter (CR-200, Minolta) and CDR imaging system were used to acquire CIELAB (CIE L*, a*, and b*) tristimulus values and RGB image values, respectively. A cost function was defined using these sample data sets and then a minimization algorithm was applied to obtain an optimized conversion matrix for our imaging system and illumination conditions. CIELAB color space values (L*, a*, and b*) obtained with the chromameter and CDR color images were compared to assess the accuracy of the derived matrix. RESULTS: In measurements using in vitro standard color patch or in vivo human skin samples, use of the optimized conversion matrix resulted in a good correlation with standard chromameter values for PWS human skin sites. CONCLUSIONS: The cost function minimization algorithm resulted in an optimized conversion matrix for our CDR imaging system. Use of the optimized matrix improved the utility of CDR color image analysis as a simple non-contact measurement technique to monitor quantitatively PWS response to laser therapy.

Color↗