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PubMed1999

Optimal pH control of batch processes for production of curdlan by Agrobacterium species.

We sought an optimal pH profile to maximize curdlan production in a batch fermentation of Agrobacterium species. The optimal pH profile was calculated using a gradient iteration algorithm based on the minimum principle of Pontryagin. The model equations describing cell growth and curdlan production were developed as functions of pH, sucrose concentration, and ammonium concentration, since the specific rates of cell growth and curdlan production were highly influenced by those parameters. The pH profile provided the strategy to shift the culture pH from the optimal growth condition (pH 7.0) to the optimal production one (pH 5.5) at the time of ammonium exhaustion. By applying the optimal pH profile in the batch process, we obtained significant improvement in curdlan production (64 g L-1) compared to that of constant pH operation (36 g L-1).

Journal Article↗

PubMed1997

Optimal immunocytochemical and flow cytometric detection of P-gp, MRP and LRP in childhood acute lymphoblastic leukemia.

The clinical relevance of multidrug resistance (MDR)-related proteins in childhood acute lymphoblastic leukemia (ALL) is largely unknown. The diversity of techniques, fixation methods, storage of cells (fresh or cryopreserved) etc, may contribute to discrepancies observed between several studies. We therefore optimized the detection of P-glycoprotein (P-gp), MDR-associated protein (MRP) and lung resistance-related protein (LRP) by immunocytochemistry and flow cytometry in childhood ALL cells. Thirteen fixation methods were compared using six antibodies in both immunocytochemistry and flow cytometry. The optimal fixation for P-gp (C219, MRK16), MRP (MRPr1) and LRP (LRP56) was a mixture of 2% (v/v) formaldehyde solution and acetone incubated for only 10 s at room temperature (FAc). For MRP recognized by MRPm6, the optimal fixation condition was acetone for 5 min at room temperature in immunocytochemistry, and methanol for 15 min at -20 degrees C in flow cytometry. P-gp staining by 4E3 was strongly antibody batch-dependent; on cytospins FAc fixation was optimal, but inconclusive data were obtained by flow cytometry. The optimized fixation conditions on fresh samples revealed a day-to-day variation in staining (both increasing and decreasing) in one third of the immunocytochemical tests. In flow cytometry the day-to-day variation in the fluorescence index was -1 +/- 22%. In both techniques, staining was comparable between fresh and cryopreserved cells. We recommend the use of the above mentioned fixation methods in order to study the clinical relevance of P-gp, MRP and LRP in childhood ALL.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Phase-specific optimization of multiple endotoxin-protein production with genetically engineered Bacillus thuringiensis.

An optimization approach was designed to specifically study the toxin-expression phase of the fermentation process of a genetically engineered Bacillus thuringiensis strain expressing dual toxin proteins (CryI and CryIII). The study has resulted in the discovery of important nutrient and process factors affecting toxin-protein yield. The results show that the existence of nitrogen sources in the medium during the toxin-expression phase is detrimental to the toxin-protein expression, while a high carbon-source level (40 g/l) encouraged protein expression. The study also suggests that the depletion of nitrogen source is the trigger for B. thuringiensis to initiate sporulation and toxin expression. A temperature setting of 28 degrees C for B. thuringiensis fermentation processes is optimal for protein yield, and reduces the oxygen requirement. It was found that the optimal conditions for spore yield and for toxin-protein yield were not the same, even though sporulation and toxin formation proceed simultaneously during the fermentation process. Scale-up studies were also conducted to confirm the optimal conditions obtained from a small-scale optimization study.

Bacillus thuringiensis↗

PubMed2000

Optimization of 6-aminopenicillanic acid (6-APA) production by using a new immobilized penicillin acylase.

A new immobilized penicillin acylase (ECPVA) was obtained by covalent binding of penicillin acylase from Streptomyces lavendulae on Eupergit C. Enzymic hydrolysis of penicillin V catalysed by ECPVA was optimized using a 2(3) factorial design of experiments, and the selected parameters for this study were pH, temperature and substrate concentration. The immobilized enzyme showed an optimal pH value of 9.5-10.5, and an optimal temperature of 60 degrees C, whereas its soluble counterpart showed the same optimal pH value and a lower optimal temperature of 50 degrees C.

Enzymes, Immobilized↗

PubMed2004

Statistical optimization of tannase production from Penicillium variable using fruits (chebulic myrobalan) of Terminalia chebula.

Statistically based experimental designs were applied to the optimization of cultural conditions for tannase production, an enzyme of great importance, from Penicillium variable. First, D-optimal design was used to evaluate the effects of variables, including concentrations of substrate (chebulic myrobalan, fruits of the tree Terminalia chebula ), pH, inoculum density, agitation and incubation period, on tannase production. The optimum value of pH and inoculum density thus obtained was 5.0 and 5 x 10(7) spores/50 ml respectively. Among these variables, substrate concentration, agitation and incubation period were identified to have the significant effects. Subsequently, the concentrations of substrate, agitation and incubation period were optimized using central composite design. The optimum values of the parameters thus obtained from the response surface methodology were 5.8 g of the substrate/50 ml of the medium, pH 5.0, 5 x 10(7) spores/50 ml of inoculum density, 150 rev./min agitation rate and 72 h of incubation period. The subsequent verification experiments confirmed the validity of the models. This optimization strategy led to a 2.4-fold increase in the enzyme production from 13.6 units/ml obtained in D-optimal design to 33 units/ml in central composite design.

Carboxylic Ester Hydrolases↗

PubMed1990

A comparison of habitual and derived optimal voice fundamental frequency values in normal young adult speakers.

The purpose of this study was to compare habitual (modal) and derived optimal pitch (fundamental frequency) values in 40 young adults. The individual habitual F0 values of 20 male and 20 female nonsmokers with normal larynges, normal voices, and no history of laryngeal pathology or formal vocal training were obtained from high-quality recordings of spontaneous monologue, oral reading, and sustained phonation. Optimal fundamental frequency (F0) was derived from each individual's phonational range using the 25% Method (Fairbanks, 1960; Pronovost, 1942). Using correlative analyses, the predicted optimal F0 values that were derived were compared to habitual F0 values for the male and female speaker groups, and for specific vocal tasks used to identify habitual F0 (i.e., spontaneous monologue vs. oral reading vs. sustained phonation). Results indicate that habitual F0 was not consistent with derived optimal F0 values using the 25% Method; rather, habitual F0 in our normal adults occurred between 8% and 10% up the phonational range from basal F0. Clinical implications of these data and the related limitations associated with the concept of optimal pitch (F0) are discussed.

Adult↗

PubMed2002

Statistical medium optimization and production of a hyperthermostable lipase from Burkholderia cepacia in a bioreactor.

AIM: Statistical medium optimization for maximum production of a hyperthermostable lipase from Burkholderia cepacia and its validation in a bioreactor. METHODS AND RESULTS: Burkholderia cepacia was grown in shake flasks containing 1% glucose, 0.1% KH2PO4, 0.5% NH4Cl, 0.24% (NH4)2HPO4, 0.01% MgSO4.7H2O and 1% emulsified palm oil, at 45 degrees C and pH 7.0, agitated at 250 rev min(-1) with 6-h-old inoculum (2% v/v) for 20 h. A fourfold enhancement in lipase production (50 U ml(-1)) and an approximately three fold increase in specific activity (160 U mg(-1)) by B. cepacia was obtained in a 14 litre bioreactor within 15 h after statistical optimization following shake flask culture. The statistical model was obtained using face centred central composite design (FCCCD) with five variables: glucose, palm oil, incubation time, inoculum density and agitation. The model suggested no interactive effect of the five factors, although incubation period, inoculum and carbon concentration were the important variables. CONCLUSIONS: The maximum lipase production was 50 U ml(-1), with specific activity 160 U mg(-1) protein, in a 14 litre bioreactor after 15 h in a medium obtained after statistical optimization in shake flasks. Further, the model predicted reduction in time for lipase production with reduction in total carbon supply. SIGNIFICANCE AND IMPACT OF THE STUDY: Statistical optimization allows quick optimization of a large number of variables. It also provides a deep insight into the regulatory role of various parameters involved in enzyme production.

Bacterial Proteins↗

PubMed2003

Optimization of dialysate sodium in sodium profiling haemodialysis.

Sodium profiling haemodialysis is a modified method of sodium gradient dialysis during which dialysate sodium follows a time-dependent profile. Sodium profiling haemodialysis has claimed to reduce intradialytic discomforts such as hypotension, muscle cramps, and disequilibrium syndrome. Having the low sodium period is an essential part of the sodium profiling haemodialysis to compensate for the sodium gain during the high sodium period. In spite of this, however, the incidence of interdialytic complications that results from the excessive sodium gain has been reported in previous literature. Making the prediction of optimal dialysate sodium concentration for isonatric dialysis is practically very difficult since too many variables influence the sodium gradient, including the initial plasma sodium and tonicity and/or dialysis dynamics that differ from patient to patient and from treatment to treatment. As for sodium profiling haemodialysis, complexities are added further since details of profile, such as type and form of profile, or initial, terminal, or time-distribution of dialysate sodium are varied considerably. We have recently reported that the intradialytic sodium balance and interdialytic weight gain are directly related to the time-averaged concentration of dialysate sodium (TACNa). The dialysate sodium can be optimized using this concept of TACNa for sodium profiling dialysis. TACNa should be approximately 0.5-0.8 mmol/L lower than patient's predialysis serum sodium concentrations to achieve a sodium balance neutral dialysis. In that study the optimal TACNa, seems to be between 137.8 and 143.5 mmol/L. Such an optimal value should be defined for the individual centres based on their profile protocols for clinical use. In the future, dialysate sodium should be optimized based on the exact prediction of the postdialysis plasma sodium levels.

Hemodialysis Solutions↗

PubMed2001

Atrioventricular interval optimization and exercise tolerance.

Modern pacemakers offer many programming options regarding the AV interval including the ability to vary AV intervals depending on whether atrial activity is paced or spontaneous and to shorten AV intervals with increasing rates. To determine if optimization of these features improves exercise tolerance, 14 patients with intact sinus node function and AV block treated with dual chamber pacemakers were enrolled in a randomized double-blind crossover trial. Doppler echocardiographic measurements of cardiac index and mitral flow were assessed over a range of programmable AV intervals at rest to determine each patient's optimal AV interval. Eleven patients completed serial graded exercise tests with spiroergometry after randomly programming the AV interval three ways in a crossover manner: fixed AV interval = 150 ms without rate adaptation (150/Fixed), fixed AVinterval = 150 ms with rate adaptation (150/R), or optimized AV interval with rate adaptive AV interval shortening (optimized/R). Exercise capacity was determined by maximum oxygen uptake. Ten men and four women, age 64 +/- 8 years, were enrolled. At rest, optimization of the AVintervalimproved the cardiac index by 21% (P < 0.001) and mitral flow by 13.4% (P < 0.001) when compared to least-favorable AV intervals. During exercise, no differences in maximum heart rates were noted. Maximum oxygen uptake was increased in both groups with rate adaptive AVinterval shortening when compared tofixed AVinterval without rate adaptation: 13.9% (adjusted P < 0.04) and 14.6% (adjusted P < 0.02) in optimized/R and 150/R, respectively. No differences were noted between optimized/R and 150/R. In conclusion, rate adaptive AV interval shortening improved exercise tolerance independent of changes in heart rate. However, optimization of the AV interval with Doppler echocardiography at rest did not further improve exercise capacity.

Atrial Function↗

PubMed2003

Impedance cardiography for atrioventricular interval optimization during permanent left ventricular pacing.

Left ventricular (LV) pacing is increasingly used in the management of congestive heart failure. Optimization of the atrioventricular (AV) interval is essential to maximize the hemodynamic benefits of this therapy. Although Doppler echocardiography (echo) is the most widely used method, it is time-consuming, expensive, and operator-dependent. We examined the value of an impedance cardiography (IC)-based method of cardiac output (CO) measurement to optimize the AV interval in 5 men and 1 woman (mean age = 72 +/- 11 years) during permanent LV pacing with a 4.8 Fr unipolar coronary sinus pacing lead. Simultaneous measurements of CO by IC and echo were performed at AV intervals of 50, 80, 110, 150, 180, and 225 ms during DDD pacing at 85 beats/min. The optimal AV interval varied between 110 and 180 ms. In 5 of 6 patients (83%), the optimal AV interval by echo and IC was identical. While CO measurements were higher with IC than with echo (6.1 +/- 0.4 L/min vs 4.7 +/- 0.3 L/min, P < 0.05), CO measurements by IC and echo were closely correlated r = 0.67, P < 0.001). In conclusion, our initial experience suggests that IC is a reliable method of AV interval optimization during LV pacing. IC and echo measurements of CO during LV pacing were closely correlated.

Aged↗

PubMed2003

Programming optimal atrioventricular delay in dual chamber pacing using peak endocardial acceleration: comparison with a standard echocardiographic procedure.

Optimization of programmed atrioventricular delay in dual chamber pacing is essential to the hemodynamic efficiency of the heart. Automatic AV delay optimization in an implanted pacemaker is highly desirable. Variations of peak endocardial acceleration (PEA) with AV delay at rest correlate well with echocardiography derived observations, particularly with end-diastolic filling and mitral valve closure timings. This suggests the possibility of devicing a procedure for the automatic determination of the optimal AV delay. The aim of this study was to compare a proposed algorithm for optimal AV delay determination with an accepted echocardiographic method. Fifteen patients with high degree AV block received BEST-Living pacing systems. Automatic AV delay scans were performed at rest (60-300 ms in 20-ms steps with 60 beats per step) in DDD at 90 ppm, while simultaneously recording cycle-by-cycle PEA values, which were averaged for each AV delay to obtain a PEA versus AV delay curve. Nonlinear regression analysis based on a Boltzmann sigmoid curve was performed, and the optimal AV delay (OAVD) was chosen as the sigmoid inflection point of the regression curve. The OAVD was also evaluated for each patient using the Ritter echocardiographic method. Good sigmoid fit was obtained in 13 of 15 patients. The mean OAVD obtained by the PEA sigmoid algorithm was 146.9 +/- 32.1 ms, and the corresponding result obtained by echocardiography was 156.4 +/- 34.3 ms (range 31.8-39.7 ms). Correlation analysis yielded r = 0.79, P = 0.0012. In conclusion, OAVD estimates obtained by PEA analysis during automatic AV delay scanning are consistent with those obtained by echocardiography. The proposed algorithm can be used for automatic OAVD determination in an implanted pacemaker pulse generator.

Aged↗

PubMed2001

Optimal reading speed in simulated cataract: development of a potential vision test.

Previous studies suggest that optimal reading speed is unaffected by cataract, yet is significantly reduced in age-related macular disease. This raises the question of whether a reading speed test could be developed to assess potential vision after cataract surgery. In this study, 20 young subjects, with and without a simulation of dense cataract, read aloud Bailey-Lovie word charts. From the results, critical print size, optimal reading speed and word acuity were calculated. The simulated cataract reduced word acuity and increased the critical print size, yet optimal reading speed remained unchanged. Measurements were also taken with the charts in reversed contrast polarity. Reversing the contrast polarity of the charts improved the word acuity and optimal reading speed with the cataract simulation. The results suggest that optimal reading speed could be used as a potential vision test. Further investigations using patients with cataract and ARMD are required.

Adult↗

PubMed2002

Dual renin-angiotensin system blockade at optimal doses for proteinuria.

BACKGROUND: The antiproteinuric effect of combining the angiotensin-converting enzyme (ACE) inhibitor lisinopril and the angiotensin II (Ang II) antagonist losartan was compared to that of the optimal antiproteinuric doses of monotherapy. METHODS: To this purpose, lisinopril and losartan were studied in 9 nondiabetic renal patients with median proteinuria 4.5 g/day (95% CI, 3.5, 6.4), creatinine clearance of 80 mL/min (95% CI, 66, 96), and mean arterial pressure (MAP) of 102 mm Hg (95% CI, 93, 112). First, in two protocols with six-week treatment periods per dose, the optimal antiproteinuric dose of each drug was established in each patient. Losartan and lisinopril were used in randomized order, each preceded by a baseline period without medication. The doses of losartan (mg/day) were 50, 100, 150, and again 50. The lisinopril doses were 10, 20, 40, and again 10. After the second protocol, patients were treated with a combination, using the optimal antiproteinuric doses established for the individual drugs. RESULTS: The antiproteinuric response by losartan was optimal at 100 mg (-46%; 95% CI, -60, -24%), being larger than at the 50 mg dose (-27%; 95% CI, -42, -4%, P < 0.05), but not different from the 150 mg dose (-46%; 95% CI, -58; -20%). Proteinuria decreased further at each up-titration step of lisinopril to -75% (95% CI, -85, -43%) at the 40 mg dose. Combination therapy reduced proteinuria more effectively (-85%; 95% CI, -96, -58) than monotherapy with losartan, and to a lesser extent than with lisinopril. Optimal blood pressure responses were obtained at similar doses. CONCLUSIONS: Dose-titration with a renin-angiotensin system blocker, followed by add-on therapy is highly effective in order to reduce proteinuria. The safety of this regimen needs to be addressed in future studies.

Adult↗

PubMedDate not supplied

Development of an optimized additive solution containing ascorbate-2-phosphate for the preservation of red cells with retention of 2,3 diphosphoglycerate.

An additive solution containing adenine, ascorbate-2-phosphate, sodium phosphate, dextrose, and saline was developed for packed red cell preservation. The combination of all components was simultaneously optimized so that the resulting solution produced the maximum retention of both red cell adenosine triphosphate (ATP) and 2,3 diphosphoglycerate (2,3 DPG) concentrations. Fourteen nutrient combinations were tested; each combination was evaluated for 42 days of storage using cells from three donors. The nutrient combinations were chosen with the aid of a computerized experimental design process. Results of the experiments were modeled by regression analysis, and the model was optimized to produce the "best" formulation for simultaneous maintenance of ATP and 2,3 DPG. The resulting mathematically optimal formulation was tested in the laboratory using 10 units of red cells. With this solution, it was possible to store red cells for 42 days with retention of 45 to 55 percent of the initial ATP and 85 to 150 percent of the initial 2,3 DPG. Red cell lysis was low (0.8 percent), and most of the cells were biconcave discs (by scanning electron microscopy) at the end of storage. The studies were carried out in an efficient manner by using computer-optimized experimental design techniques coupled with multiple regression modeling and subsequent computer optimization of the models. This experimental approach has potential application to many current blood banking procedures. This additive solution should maintain viable red cells for 42 days. In addition, the solution will maintain red cell 2,3 DPG throughout storage.

2,3-Diphosphoglycerate↗

PubMed1993

Plan Optimization and Dose Evaluation in Brachytherapy.

Today's imaging and computer technology has made significant advances in brachytherapy optimization and evaluation possible. Optimization may be of source strength or of source position (or both). An objective function of achieved versus desired doses is minimized, a global minimum being associated with an analytic solution and a local minimum with an iterative solution. Optimization of source strengths is shown useful in planning low-dose-rate brachytherapy either of cervical cancer, using a remote afterloader with pneumatically loaded cesium 137 sources, or of recurrent enodmetrial cancer, using a vaginal cylinder and iridium 192 seeds in ribbons. Source position optimization, on the other hand, is exemplified by permanent percutaneous implants for prostate cancer or by temporary stereotactic implants for brain tumors with iodine 125 sources of low and high strength, respectively. Evaluation of the true minimum peripheral dose generally requires that three-dimensional images be available. Dose-volume histograms serve to describe both dose uniformity within the treatment volume and the extent to which normal tissues are being irradiated. With respect to the future, deconvolution and simulated annealing techniques are being explored for brachytherapy optimization, and we may expect greater emphasis on the biologically effective dose in brachytherapy evaluation.

Journal Article↗

PubMed1983

Diplegic cerebral palsy in Swedish term and preterm children. Differences in reduced optimality, relations to neurology and pathogenetic factors.

An unselected series of 93 Swedish diplegic children born in 1969-1976 and subgrouped into 49 term (TDC) and 44 preterm (PDC) cases were analyzed for differences in reduced optimality in pre- and perinatal conditions, these also being related to degree of handicap, associated neurology and conventional pathogenetic grouping. Comparisons of the reduced optimality with those of a dyskinetic and a control series were also made. TDC were shown to have more severe handicaps and more additional neurologic abnormalities than PDC. The profile of reduced optimality was weighted in TDC to items pointing to fetal maladjustment/deprivation and birth asphyxia and in PDC to items accompanying preterm birth and to postpartal items. The optimality of diplegics was in general more reduced than in controls and less than in dyskinetics. This was especially true for TDC. Differences in the background mechanisms of the diplegia between TDC and PDC were indicated from dissimilarities in the combined patterns of reduced optimality and conventional pathogenetic grouping. Postpartal complications predominated among PDC. A prepartal factor as the only cause of the diplegia was likely in 41% of TDC, and as a contributory cause in another 24%. Birth asphyxia, present in 31% of the TDC, was never the only risk factor among infants born at term.

Abnormalities, Multiple↗

PubMed2004

Optimal laser control of ultrafast photodissociation of I2- in water: mixed quantum/classical molecular dynamics simulation.

A linearized optimal control method in combination with mixed quantum/classical molecular dynamics simulation is used for numerically investigating the possibility of controlling photodissociation wave packets of I(2)(-) in water. Optimal pulses are designed using an ensemble of photodissociation samples, aiming at the creation of localized dissociation wave packets. Numerical results clearly show the effectiveness of the control although the control achievement is reduced with an increase in the internuclear distance associated with a target region. We introduce effective optimal pulses that are designed using a statistically averaged effective dissociation potential, and show that they semiquantitatively reproduce the control achievements calculated by using optimal pulses. The control mechanisms are interpreted from the time- and frequency-resolved spectra of the effective optimal pulses.

Journal Article↗

PubMed2005

On the use of optimal internal vibrational coordinates for symmetrical bent triatomic molecules.

The use of generalized internal coordinates for the variational calculation of excited vibrational states of symmetrical bent triatomic molecules is considered with applications to the SO2, O3, NO2, and H2O molecules. These coordinates depend on two external parameters which can be properly optimized. We propose a simple analytical method to determine the optimal internal coordinates for this kind of molecules based on the minimization with respect to the external parameters of the zero-point energy, assuming only quadratic terms in the Hamiltonian and no quadratic coupling between the optimal coordinates. The optimal values of the parameters thus obtained are shown to agree quite well with those that minimize the sum of a number of unconverged energies of the lowest vibrational states, computed variationally using a small basis function set. The unconverged variational calculation uses a basis set consisting of the eigenfunctions of the uncoupled anharmonic internal coordinate Hamiltonian. Variational calculations of the excited vibrational states for the four molecules considered carried out with an increasing number of basis functions, also evidence the excellent convergence properties of the optimal internal coordinates versus those provided by other normal and local coordinate systems.

Journal Article↗