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PubMed2004

Optimization of Serratia marcescens lipase production for enantioselective hydrolysis of 3-phenylglycidic acid ester.

Lipase production and cell growth of Serratia marcescens ECU1010 were optimized in shake flasks, with lipase production being enhanced 9.5-fold (4,780 U/l) compared with the initial activity (500 U/l). Optimal carbon and nitrogen sources were Tween-80 and peptone, and the optimal ratio of Tween-80 to peptone was 1:3. The optimized cultivation conditions were 25 degrees C and pH 6.5. Lipase activity, particularly specific activity, could be improved by decreasing the cultivation temperature from 35 to 25 degrees C. Enzyme stability was significantly improved by simple immobilization with synthetic adsorption resin no. 8244. After five reaction cycles, enzyme activity decreased only very slightly, while enantioselectivity of the preparation remained constant, and the ees (enantiomeric excess of the remaining substrate) achieved in all cases was higher than 97%. The resin-8244-lipase preparation can be used for efficient enantioselective hydrolysis of trans-3-(4'-methoxyphenyl)glycidic acid methyl ester [(+/-)-MPGM], a key intermediate in the synthesis of Diltiazem.

Enzyme Stability↗

PubMed2007

Optimal planar flow network designs for tissue engineered constructs with built-in vasculature.

Convective delivery of nutrients is important to enhance mass transport within tissue engineered (TE) products. Depending on the target tissue, an ideal TE product will have an integrated microvasculature that will eliminate mass transport limitations that can occur during product growth in vitro and integration in vivo. A synthetic approach to develop microvasculature involves development of network designs with efficient mass transfer characteristics. In this paper, utilizing a planar bifurcating network as a basis, we develop an approach to design optimal flow networks that have maximum mass transport efficiency for a given pressure drop. We formulated the optimization problem for a TE skin product, incorporating two types of duct flow, rectangular and square, and solved using a generalized reduced gradient algorithm. Under the conditions of this study, we found that rectangular ducts have superior mass transport characteristics than square ducts. Microvascular area per volume values obtained in this work are significantly greater than those reported in the literature. We discuss the effect of network variables such as porosity and generations on the optimal designs. This research forms the engineering basis for the rational development of TE products with built-in microvasculature and will pave the way to design complex flow networks with optimal mass transfer characteristics.

Microcirculation↗

PubMed2006

Accuracy of optimized chemical-exchange parameters derived by fitting CPMG R2 dispersion profiles when R2(0a) not = R2(0b).

The transverse relaxation rate, R2, measured as a function of the effective field (R2 dispersion) using a Carr-Purcell-Meiboom-Gill (CPMG) pulse train, is well suited to detect conformational exchange in proteins. The dispersion data are commonly fitted by a two-site (sites a and b) exchange model with four parameters: the relative population, pa, the difference in chemical shifts of the two sites, deltaomega, the correlation time for exchange, tau(ex), and the intrinsic relaxation rate (i.e., transverse relaxation rate in the absence of chemical exchange), R2(0). Although the intrinsic relaxation rates of the two sites, R2(0a) and R2(0b), can differ, they are normally assumed to be the same (i.e., R2(0a) = R2(0b) = R2(0)) when fitting dispersion data. The purpose of this investigation is to determine the magnitudes of the errors in the optimized exchange parameters that are introduced by the assumption that R2(0a) = R2(0b). In order to accomplish this goal, we first generated synthetic constant-time CPMG R2 dispersion data assuming two-site exchange with R2(0a) not equal R2(0b), and then fitted the synthetic data assuming two-site exchange with R2(0) = R2(0a) = R2(0b). Although all the synthetic data generated assuming R2(0a) not equal R2(0b) were well fitted (assuming R2(0a) = R2(0b)), the optimized values of pa and tau(ex) differed from their true values, whereas the optimized values of deltaomega values did not. A theoretical analysis using the Carver-Richards equation explains these results, and yields simple, general equations for estimating the magnitudes of the errors in the optimized parameters, as a function of (R2(0a) - R2(0b)).

Bias↗

PubMed2006

Evaluation and optimization of the conditions for an improved ferulic acid intercalation into a synthetic lamellar anionic clay.

PURPOSE: The aim of the study is to optimize the intercalation conditions of ferulic acid (FERH), an antioxidant compound, into Mg-Al-hydrotalcite for a safe skin photoprotection. METHODS: The intercalation products were prepared incubating hydrotalcite (HTlc) in aqueous solutions of FERH sodium salt at different temperatures over 4 and 8 days. Quantitative determination of intercalated FERH was performed by thermogravimetric analysis and morphology by scanning electron microscopy (SEM). FERH stability study was carried out at different pHs and temperatures. FERH was analyzed by reversed phase-high-performance liquid chromatography. Response surface methods (RSMs) were used to assess optimal intercalation conditions and FERH stability. RESULTS: In all intercalation products, FERH content was found to be about 48% w/w except when the intercalation process was carried out at 52 degrees C for 8 days and at 60 degrees C for both 4 and 8 days, which resulted to be 40.39, 39.99, and 34.99%, respectively. The RSM designs showed that intercalation improvement can be achieved by working at pH 6, at temperatures below 40 degrees C, and over 4 days of incubation. CONCLUSIONS: The optimal conditions for a proper FERH intercalation were assessed. The development of a new optimized protocol may improve HTlc-FER complex performances and safety by augmenting dosage and reducing the presence of harmful reactive species in the final formulation.

Aluminum Hydroxide↗

PubMed2006

Optimization design of thumbspica splint using finite element method.

De Quervain's tenosynovitis is often observed on repetitive flexion of the thumb. In the clinical setting, the conservative treatment is usually an applied thumbspica splint to immobilize the thumb. However, the traditional thumbspica splint is bulky and heavy. Thus, this study used the finite element (FE) method to remove redundant material in order to reduce the splint's weight and increase ventilation. An FE model of a thumbspica splint was constructed using ANSYS9.0 software. A maximum lateral thumb pinch force of 98 N was used as the input loading condition for the FE model. This study implemented topology optimization and design optimization to seek the optimal thickness and shape of the splint. This new design was manufactured and compared with the traditional thumbspica splint. Ten thumbspica splints were tested in a materials testing system, and statistically analyzed using an independent t test. The optimal thickness of the thumbspica splint was 3.2 mm. The new design is not significantly different from the traditional splint in the immobilization effect. However, the volume of this new design has been reduced by about 35%. This study produced a new thumbspica splint shape with less volume, but had a similar immobilization effect compared to the traditional shape. In a clinical setting, this result can be used by the occupational therapist as a reference for manufacturing lighter thumbspica splints for patients with de Quervain's tenosynovitis.

De Quervain Disease↗

PubMed2006

Optimal control in a model of dendritic cell transfection cancer immunotherapy.

We construct a population dynamics model of the competition among immune system cells and generic tumor cells. Then, we apply the theory of optimal control to find the optimal schedule of injection of autologous dendritic cells used as immunotherapeutic agent. The optimization method works for a general ODE system and can be applied to find the optimal schedule in a variety of medical treatments that have been described by a mathematical model.

Algorithms↗

PubMed1999

Optimal tobramycin dosage in patients with cystic fibrosis--evidence for predictability based on previous drug monitoring.

A retrospective analysis of files of patients with cystic fibrosis and pulmonary exacerbations was performed to investigate whether an individual dosage of tobramycin once established by serum level determination allows a reliable prediction of the adequate dosage in a consecutive exacerbation. All patients hospitalized > or = 2 times between May 1997 and September 1998 with pulmonary exacerbation due to Pseudomonas aeruginosa infection susceptible to tobramycin were included. The initial dosage to tobramycin was 5 mg/kg body weight every 12 h followed by drug level determinations to establish the optimal dose. In a consecutive exacerbation the same dosage per kg body weight was used again and drug level determinations were repeated. Sixteen patients (six female = 38%) with a mean age of 24 years (median: 26 years, range: 9-33) were hospitalized for 49 pulmonary exacerbations (2-6 per patient, mean: 3, median: 2.5). During the first episode of tobramycin treatment in the study period all trough levels were < 2 microg/ml (median: 0.6) and the peak levels were 7.1-16.9 microg/ml (median: 11.9). In four patients the peak level was > 12 microg/ml. In 28 consecutive episodes the dosage of tobra myci n was chosen based on optimal results of previous drug level monitoring and in 27 instances (96%) the previously established optimal dose was confirmed. In five consecutive episodes the tobramycin dosage had been increased erroneously and this resulted in abnormally high peak levels in three cases. These findings suggest that a safe and therapeutic tobramycin dosage in an individual patient with cystic fibrosis is predictable based on a previously established optimal dosage.

Adult↗

PubMed1992

Line bisecting as a predictor of personal optimism and desirability of risky behaviors.

Our goal was to test whether current hemisphere predominance is a predictor of scores on standardized measures of personal optimism and preference for risk. In two between-subject experiments, current hemisphere predominance was measured by the direction and extent of line bisecting errors. Pearson correlations and median splits of the line bisecting errors showed significantly greater personal optimism and preference for risk with left hemisphere predominance. These results support previous research in which manipulation of hemisphere predominance produced similar effects on personal optimism in normal individuals and on risk taking in lesioned and normal samples. We conclude that the association of optimism and risk with left hemisphere predominance can be observed in resting as well as in manipulated situations.

Adolescent↗

PubMed1988

Optimal conditions for hybridization with oligonucleotides: a study with myc-oncogene DNA probes.

We present a study on the refinement of filter-hybridization conditions for a series of synthetic oligonucleotides in the range from 17 to 50 base residues in length. Experimental conditions for hybridization and the subsequent washing steps of the filter were optimized for different lengths of the synthetic oligonucleotides by varying the formamide concentration and washing conditions (temperature and monovalent cation concentration). Target DNA was immobilized to the nitrocellulose filter with the slot blot technique. The sequences of the synthetic oligonucleotides are derived from the third exon of the human oncogene c-myc and the corresponding viral gene v-myc and the G + C content was between 43 and 47%. Optimal conditions for hybridization with a 82% homologous 30-mer and 100% homologous 17-, 20-, 25-, 30-, and 50-mers were found to be a concentration of formamide of 15, 15, 30, 30, 40, and 50%, respectively. Optimal conditions for washing were 0.5X standard sodium citrate (SSC) at 42 degrees C for 2 X 15 min. The melting temperature for these optimal hybridization and washing conditions was calculated to be up to 11 degrees C below the hybridization temperature actually used. This confirms that the duplexes are more stable than expected. The melting points for 17-, 20-, and 30-mers were measured in the presence of 5X SSC and found to be 43, 58, and 60 degrees C, respectively. Competition between double- and single-stranded DNA probes to the target DNA was investigated. The single-stranded DNA probes were about 30- to 40-fold more sensitive than the double-stranded DNA probes.

Base Sequence↗

PubMed1989

Optimization of electroporation for transfection of mammalian cell lines.

Electroporation can be a highly efficient method for introducing DNA molecules into cultured cells for transient expression of genes or for permanent genetic modification. However, effective transformation by electroporation requires careful optimization of electric field strength and pulse characteristics. We have used the transient expression of the firefly luciferase gene as a rapid and sensitive indicator of gene expression to describe the effects on transfection efficiency of altering electroporation field strength and shape. Using the luciferase assay, we investigated the correlation of cell viability with optimal transfection efficiency and determined the optimal parameters for a number of phenotypically distinct mammalian cell lines derived from the nervous and immune systems. The efficiency of electroporation under optimal conditions was compared with that obtained using DEAE-dextran or calcium phosphate-mediated transformation. Transfection by electroporation using square wave pulses, as opposed to exponentially decaying pulses, was found to be significantly increased by repetitive pulses. These methods improve the ability to obtain high efficiency gene transfer into many mammalian cell types.

Animals↗

PubMed1991

Optimal transcranial magnetic stimulation sites for the assessment of motor function.

The optimal placement sites for eliciting motor evoked potentials from the abductor digiti minimi and abductor hallucis muscles by means of transcranial magnetic stimulation were determined using a commercially available circular coli. Fifty volunteers were used for the study. The ability to elicit responses was found to be strongly dependent upon the scalp placement of the stimulator coil. The effects of altering the direction of current flow in the coil were tested on two different sets of volunteers: clockwise in one and counterclockwise in the other. It influenced only the locations of the sites which were optimal for eliciting responses from the abductor hallucis muscles and not those which were optimal for eliciting responses from the abductor digiti minimi muscles. Response latencies were found to be significantly dependent only upon volunteers' heights and not on their sex, age, or weight or the stimulus intensities used to elicit responses. No previous studies have defined the optimal scalp placements for eliciting responses from the lower extremities. This information may have clinical importance for making reliable assessments of patients with significantly impaired motor function.

Action Potentials↗

PubMed1979

Algebraic framework of an optimization problem in diagnosis.

A formal analysis of an optimization problem in medical diagnosis is presented. The mathematical model of the diagnostic process corresponds in this work to an abstract machine definition which is based on the following sets and functions: Set of possible pathological states (diseases) of a patient, set of diagnostic tests (examination methods), set of all possible results of the tests (symptoms and signs), function which chooses successive tests, function performing a test (i.e., assigning to a given test its result), function assigning to each symptom a certain subset of the set of diseases. For a given abstract machine a class of pairs of graphs is formed; their analysis leads to the identification of a class of pairs of subgraphs which corresponds to an optimized diagnostic procedure. The optimization consists of a comparison of the distances between the initial and terminal vertices of the graphs and of a choice of a shortest route to a final diagnosis. For the considered class of pairs of subgraphs a mathematical model of the optimized diagnostic process is reconstructed.

Diagnosis↗

PubMed1989

Multivariable optimization of cycling biomechanics.

Relying on a biomechanical model of the lower limb which treats the leg-bicycle system as a five-bar linkage constrained to plane motion, a cost function derived from the joint moments developed during cycling is computed. At constant average power of 200 W, the effect of five variables on the cost function is studied. The five variables are pedalling rate, crank arm length, seat tube angle, seat height, and longitudinal foot position on the pedal. A sensitivity analysis of each of the five variables shows that pedalling rate is the most sensitive, followed by the crank arm length, seat tube angle, seat height, and longitudinal foot position on the pedal (the least sensitive). Based on Powell's method, a multivariable optimization search is made for the combination of variable values which minimize the cost function. For a rider of average anthropometry (height 1.78 m, weight 72.5 kg), a pedalling rate of 115 rev min-1, crank arm length of 0.140 m, seat tube angle of 76 degrees, seat height plus crank arm length equal to 97% of trochanteric leg length, and longitudinal foot position on the pedal equal to 54% of foot length correspond to the cost function global minimum. The effect of anthropometric parameter variations is also examined and these variations influence the results significantly. The optimal crank arm length, seat height, and longitudinal foot position on the pedal increase as the size of rider increases whereas the optimal cadence and seat tube angle decrease as the rider's size increases. The dependence of optimization results on anthropometric parameters emphasizes the importance of tailoring bicycle equipment to the anthropometry of the individual.

Anthropometry↗

PubMed1989

Shape optimal design of the stem of a cemented hip prosthesis to minimize stress concentration in the cement layer.

An optimal shape of the metal stem of a cemented total hip prosthesis minimizing stress concentration in the cement layer was searched for. A gradient projection method of numerical optimization and a finite element method of stress analysis were employed. A two-dimensional model of the femoral part of a total hip prosthesis was derived equivalent to a simplified three-dimensional axisymmetric model. The result of the stress analysis of the two-dimensional model compared favorably with that of the three-dimensional axisymmetric model. Using this two-dimensional model, an optimal shape of the stem, minimizing stress concentration in the cement layer, was obtained by a gradient projection method and the shape was checked again by the three-dimensional finite element analysis. The resulting optimal shape of the stem profile was in good agreement with conventional ones, except in the proximal region where a significant amount of stress reduction in the cement layer was achieved by tapering the stem to the limit that the stem still could withstand the increased stem stress.

Bone Cements↗

PubMed1991

Optimization of skeletal configuration: studies of scoliosis correction biomechanics.

A scheme for optimizing configurations in models of skeletal structures is presented. Use of the scheme is illustrated through determination of biomechanically optimal correction of a right-thoracic scoliosis by passive brace and active muscle forces. The locations and magnitudes of the passive brace forces, and the trunk muscle groups and their corresponding contraction intensity magnitudes that would optimally correct the geometric deformities of the spine were determined. The results suggest that, from a biomechanical viewpoint, both brace and muscle forces are capable of substantial correction of a model thoracic scoliosis. However, comparison of model results with long-term clinical results suggests that even under optimal conditions it is unlikely that scoliosis can be fully corrected by passive brace forces or active muscle contractions.

Biomechanical Phenomena↗

PubMed1995

Optimizing the determination of the body center of mass.

The position or trajectory of the body center of mass (COM) is often a parameter of interest when studying posture or movement. For instance, in balance control studies the body COM can be related to the ground reaction force or to the base of support. Since small displacements of the body COM are important in balance control studies, it is essential to obtain valid estimates of the body COM. The main source of error in the determination of the body COM is the estimation of the masses and centers of mass of the body segments. Especially the determination of the trunk COM is prone to error. In the current study five subjects maintained three postures, differing in trunk angle, during a few seconds. The relation between the center of pressure of the ground reaction force and the vertical projection of the body COM during the postures was used to optimize the trunk COM position. Additionally the subjects performed two lifting movements. The validity of the body COM trajectory estimation during the lifting movements, both with and without optimized trunk COM, was checked by relating the external moment of the ground reaction force with respect to the body COM to the rate of change of the angular momentum of the whole body. It was shown that the correspondence between the external moment and the rate of change of the angular momentum improved after optimization of the trunk COM. This suggests that the body COM trajectory estimation can be improved by the proposed optimization procedure.

Adult↗

PubMed1994

In vivo determination of the anatomical axes of the ankle joint complex: an optimization approach.

This study investigates the feasibility of a subject-specific three-dimensional model of the ankle joint complex for kinematic and dynamic analysis of movement. The ankle joint complex was modelled as a three-segment system, connected by two ideal hinge joints: the talocrural and the subtalar joint. A mathematical formulation was developed to express the three-dimensional translation and rotation between the foot and shank segments as a function of the two joint angles, and 12 model parameters describing the locations of the joint axes. An optimization method was used to fit the model parameters to three-dimensional kinematic data of foot and shank markers, obtained during test movements throughout the entire physiological range of motion of the ankle joint. The movement of the talus segment, which cannot be measured non-invasively, is not necessary for the analysis. This optimization method was used to determine the position and orientation of the joint axes in 14 normal subjects. After optimization, the discrepancy between the best fitting model and actual marker kinematics was between 1 and 3 mm for all subjects. The predicted inclination of the subtalar joint axis from the horizontal plane was 37.4 +/- 2.7 degrees, and the medial deviation was 18.0 +/- 16.2 degrees. The lateral side of the talucrural axis was directed slightly posteriorly (6.8 +/- 8.1 degrees), and inclined downward by 7.0 +/- 5.4 degrees. These results are similar to previously reported typical results from anatomical, in vitro studies. Reproducibility was evaluated by repeated testing of one subject, which resulted in variations of about one-fifth of the standard deviation within the group, the inclination of the subtalar joint axis was significantly correlated to the arch height and a radiographic 'tarsal index'. It is concluded that this optimization method provides the opportunity to incorporate inter-individual anatomical differences into kinematic and dynamic analysis of the ankle joint complex. This allows a more functional interpretation of kinematic data, and more realistic estimates of internal forces.

Algorithms↗

PubMed1979

An investigation of the optimal conditions for the in vivo production of immunologically sensitised rat mast cells.

Experiments were designed to develop an optimal method for inducing in vivo production of sensitised peritoneal mast cells. Rats of different strains were sensitised with whole egg-white and killed at suitable intervals to harvest the peritoneal mast cells. Release of histamine was induced in vitro by both whole egg-white and its major protein constituents, and assayed by a standard spectrofluorometric method. Wistar rats showed higher levels of sensitisation than black-hooded Lister rats; it was more convenient to harvest erythrocyte-free peritoneal mast cells from males than females. Very young (less than 150 g) and very old (greater than 300 g) rats showed sub-optimal sensitisation. Optimal sensitisation was obtained by simultaneous administration of antigen (doses of 50 micrograms whole egg-white and above) and adjuvant (1.0 ml pertussis vaccine); mast cells harvested between 20 and 50 days after the sensitising dose exhibited maximal histamine release upon in vitro challenge with 'whole' egg-white (100 micrograms). Routine use of plastic ware, and ice-cold phosphate-buffered saline (pH 7.2) for handling cells and avoidance of heparin and excessive centrifugation ensured optimal preservation of histamine-releasing capacity of the harvested peritoneal mast cells.

Aging↗