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Results for “Process optimization”

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At least 1,171 records · Page 65Linked to original sources

PubMed2005

Optimization of penicillin G acylase multipoint immobilization on to glutaraldehyde-chitosan beads.

The objective of this work was to study the immobilization of penicillin G acylase from Escherichia coli on to chitosan-glutaraldehyde beads by multipoint covalent binding. This process was optimized using a 2(3) experimental design. The parameters selected for the present study were the concentrations of glutaraldehyde, phenylacetic acid and sodium borohydride. Three responses were chosen, namely immobilization yield and stabilization factors of enzyme derivatives at high temperature and at alkaline pH. All the runs at the maximum (+1) and minimum (-1) levels were performed at random. Three experiments were performed at the centre point, coded as zero, for experimental-error estimation. With respect to immobilization yield, the main effectors were the concentrations of glutaraldehyde and phenylacetic acid. For stabilization factors at 50 degrees C and at alkaline pH, the main effectors were the concentrations of glutaraldehyde and sodium borohydride and the interaction between them.

Binding Sites↗

PubMed2003

Effects of leukapheresis protocol, cell processing and cryopreservation on the generation of monocyte-derived DC for immune therapy.

BACKGROUND: Many clinical trials of DC-based immunotherapy involve administration of monocyte-derived DCs (Mo-DC) on multiple occasion. We aimed to determine tbe optimal cell processing procedures and timing (leukapheresis, RBC depletion and cryopreservation) for generation of Mo-DC for clinical purposes. METHODS: Leukapheresis was undertaken using a COBE Spectra. Two instrument settings were compared - the standard semi-automated software (Version 4.7) (n = 10) and the fully automated software (Version 6.0) (N = 40). Density gradient centrifugation using Ficoll, Percoll, a combination of these methods or neither for RBC depletion were compared. Outcomes (including cell yield and purity) were compared for cryopreserved unmanipulated monocytes and cryopreserved Mo-DC. RESULTS: Software Version 6.0 provided significantly better enrichment for monocytes (P < 0.05) but 25% fewer total monocytes. Final Mo-DC purity was not influenced by leukapheresis or RBC depletion method, but was critically dependent on monocyte adherence. Version 6.0 produced significantly lower RBC and platelet contamination (P < 0.0005) but in vitro RBC depletion could not routinely be omitted. Only 5-6% of monocytes harvested resulted in Mo-DC (95% lost in cell processing or failing to differentiate). DISCUSSION: Cell losses remained significant despite attempts to minimise processing steps during Mo-DC generation. Reduction in RBC and platelets achieved with software version 6.0 was insufficient to offset the disadvantage of the lower monocyte yield. Substantial savings in materials and other costs can be achieved if Mo-DC for multiple treatments are generated from cryopreserved monocytes rather than from fresh monocytes.

Cell Separation↗

PubMed2001

Optimization of stereoselective ketone reduction by the white-rot fungus Merulius tremellosus ono991.

A recently isolated white-rot fungal strain, Merulius tremellosus ono991, displays high stereoselectivity during the reduction of arylketones. In order to increase the productivity and specific yield of the optically active alcohols, the culture conditions for the reduction of the model ketone compound 1'-acetonaphtone to alpha-methyl-1-naphtalenemethanol were optimized with respect to oxygen supply, choice of primary substrate and arylketone concentration. Alternative electron acceptors were also used to elucidate the role of reduction equivalents in the reduction process. The optimal yields of alpha-methyl-1-naphtalenemethanol were obtained in N2-flushed incubations with glycerol as primary substrate. The specific yield was increased from 57% to 98% compared to incubations under air with glucose. Most of the yield increase was due to N2-flushing and could be attributed to two factors. First, an increased stability of the product, alpha-methyl-1-naphtalenemethanol, in anaerobic compared to aerobic atmosphere was demonstrated. Second, fermentative metabolism increased reduced enzyme cofactors available for the reduction. Diverting reducing equivalents away from fermentation with alternative electron acceptors correlated with a decreased yield of alpha-methyl-1-naphtalenemethanol. Furthermore, the dependency of ketone reductase for common occurring metabolic reducing equivalents, NAD(P)H, was demonstrated by the reduction of 1'-acetonaphtone in cell extracts of M. tremellosus ono991.

Basidiomycota↗

PubMedDate not supplied

Seeking the competitive advantage: it's more than cost reduction.

Most organizations focus considerable time and energy on reducing operating costs as a way to attain marketplace advantage. This strategy was not inappropriate in the past. To be competitive in the future, however, focus must be placed on other issues, not just cost reduction. The near future will be dominated by service industries, knowledge management, and virtual partnerships, with production optimization and flexibility, innovation, and strong partnerships defining those organizations that attain competitive advantage. Competitive advantage will reside in clarifying the vision and strategic plan, reviewing and redesigning work processes to optimize resources and value-added work, and creating change-ready environments and empowered workforces.

Cost Control↗

PubMedDate not supplied

[Various mechanisms of regulation of lipid peroxidation in human erythrocytes after long-term exposure to hyperbaric oxygenation].

Intensity of lipid peroxidation and activity of antioxidant protection enzymes in erythrocytes were measured in three experiments with 10-24 days exposure of aquanauts under 4.6 and 5.1 MPa. It is established that there is no pathological intensification of lipid peroxidation when oxygen partial pressure in breathing gas mixture is optimal. This process is under reliable control by modulation of antioxidant enzymes activity. The high sensitivity of these research methods allows using them to determine exposure limitations under high pressure and optimal oxygen concentrations in breathing gas mixture.

Adult↗

PubMed2004

Optimization of standard patient radiographic images for chest, skull and pelvis exams in conventional x-ray equipment.

Optimized radiographic techniques for clinical images of chest, skull and pelvis using conventional single-phase, three-phase and high-frequency x-ray units for a standard patient have been developed. Optimization of image contrast and optical density was obtained by using a homogeneous phantom (PEP) and an Anderson Rando anthropomorphic phantom. Image quality was evaluated by nine radiologists in independent analyses, leading to the choice of the optimized technique. A course of action to implement and validate these techniques in other radiographic systems has also been introduced. A realistic-analytic phantom (RAP) was constructed to certify the validation process. The optimized radiographic technique was implemented in the routine of our home hospital radiodiagnostic routine, enabling a reduction in patient doses around 25, 14 and 72%, respectively, for chest, skull and pelvis exams when compared with the previously used techniques. In addition, a corresponding reduction in the x-ray tube load of 68, 14 and 62% for the respective mentioned exams has been observed. In conclusion, implemented optimal techniques can lead to a reduction in the rate of film rejection, thus contributing to a better risk-benefit relationship for the patient and cost-benefit for the radiodiagnostic facility.

Humans↗

PubMed2006

Control of electron transfer pathways in a dye-sensitized solar cell.

Using shaped laser pulses, we increase the yield of ultrafast electron injection from the sensitizer to TiO2 nanocrystals in the core part of a dye-sensitized solar cell. The temporal structure of the optimized excitation pulse is in clear correlation with nuclear oscillations in the impulsively excited dye molecule. From DFT structure optimization and normal mode analyses we identified the modes which are responsible for the oscillations. The best pulse shape suggests Impulsive Stimulated (anti-Stokes) Raman scattering as a key process of optimization.

Journal Article↗

PubMed1990

Problem solving by reference to rules or previous episodes: the effects of organized training, analogical models, and subsequent complexity of experience.

Subjects learned a microcomputer drawing package under different conditions of training organization and practice complexity. Training instructions were presented in either a random or an organized order, and with or without an analogical model of the software package. Practice trial varied in visual and logical complexity. Performance on paper-and-pencil and problem-solving tests was better following the model than following the no-model condition when practice trials were logically complex; the reverse was true when they were logically simple. Performance on the test of problem solving was also better following organized training than following randomly ordered training when practice trials were visually complex; the reverse was true following visually simple practice. We propose that the subjects performed the tasks by engaging in either episode-based or rule-based processing, and that performance was optimized when the processing used at encoding and retrieval was the same. The acquisition of skill in solving real problems is explained as procedural compilation.

Adolescent↗

PubMed2005

[Enhancement of thrombolytic activities of Carthamus tinctorius processed with fermentation with a bacillus sp. C2-13].

A processing method to enhance thrombolytic effect of Carthamus tinctorius using a fermentation technology with bacillus sp. C2-13 was investigated. The fibrinolysis and anticoagulation activity of thrombolytic extracts from an optimized fermentation process was studied using a carrageenan induced mice model. The fermented extracts resulted in significantly better thrombolytic activity, suggesting that the process was promising for use in the study and preparation of nature medicines.

Animals↗

PubMed1998

Maximum likelihood as a common computational framework in tomotherapy.

Tomotherapy is a dose delivery technique using helical or axial intensity modulated beams. One of the strengths of the tomotherapy concept is that it can incorporate a number of processes into a single piece of equipment. These processes include treatment optimization planning, dose reconstruction and kilovoltage/megavoltage image reconstruction. A common computational technique that could be used for all of these processes would be very appealing. The maximum likelihood estimator, originally developed for emission tomography, can serve as a useful tool in imaging and radiotherapy. We believe that this approach can play an important role in the processes of optimization planning, dose reconstruction and kilovoltage and/or megavoltage image reconstruction. These processes involve computations that require comparable physical methods. They are also based on equivalent assumptions, and they have similar mathematical solutions. As a result, the maximum likelihood approach is able to provide a common framework for all three of these computational problems. We will demonstrate how maximum likelihood methods can be applied to optimization planning, dose reconstruction and megavoltage image reconstruction in tomotherapy. Results for planning optimization, dose reconstruction and megavoltage image reconstruction will be presented. Strengths and weaknesses of the methodology are analysed. Future directions for this work are also suggested.

Algorithms↗

PubMed2004

Enrichment of rare cancer cells through depletion of normal cells using density and flow-through, immunomagnetic cell separation.

OBJECTIVE: To develop a reliable technique to enrich for rare cells in blood suspensions using only negative selection steps including a flow-through immunomagnetic cell separations system and by optimizing variables normally encountered during such enrichment processes. METHODS: A human breast cancer cell line was cultivated and spiked at a ratio of 1 cancer cell to 10(5) total leukocytes in buffy coat or 1 cancer cell to 10(8) total cells in whole blood samples. The final, optimized process consisted of: a red cell lysis step, immunomagnetically staining leukocytes with an anti-CD45 PE, anti- MACS sandwich, immunomagnetic sorting using a flow-through system (QMS), and a final cell analysis step using either an automated cell counter, filtration, and visual counting or a cytospin analysis. RESULTS: The final, optimized process produced a final enrichment of the rare cancer cells of 5.17 log(10) and an average, final recovery of 46%. It should be noted that a negative depletion protocol was used (i.e., no labeling of the rare cancer cells was used). CONCLUSIONS: To the authors' knowledge, no examples in the literature exist of a 5.17 log(10) enrichment of cancer cells in human blood using a negative depletion protocol. The closest example is a 4 log(10) enrichment in which two positive magnetic cell separation steps were used (none were used in this study). Ongoing studies are investigating further modifications of the precommercial, prototype flow-through immunmagnetic separation system to increase both the enrichment and recovery rate. However, even at current performance levels, the presented process could significantly improve visual and molecular analysis of rare cells in blood.

Antibodies, Monoclonal↗

PubMed2006

Model based robustness analysis of an ion-exchange chromatography step.

Process development, optimization and robustness analysis for chromatographic separation are often entirely based on experimental work and generic knowledge. This paper describes a model-based approach that can be used to gain process knowledge and assist in the robustness analysis of an ion-exchange chromatography step using a model-based approach. A kinetic dispersive model, where the steric mass action model accounts for the adsorption is used to describe column performance. Model calibration is based solely on gradient elution experiments at different gradients, flow rates, pH and column loads. The position and shape of the peaks provide enough information to calibrate the model and thus single-component experiments can be avoided. The model is calibrated to the experiments and the confidence intervals for the estimated parameters are used to account for the model error throughout the analysis. The model is used to predict the result of a robustness analysis conducted as a factorial experiment and to design a robust pooling approach. The confidence intervals are used in a "worst case" approach where the parameters for the components are set at the edge of their confidence intervals to create a worst case for the removal of impurities at each point in the factorial experiment. The pooling limit was changed to ensure product quality at every point in the factorial analysis. The predicted purities and yields were compared to the experimental results to ensure that the prediction intervals cover the experimental results.

Chromatography, Ion Exchange↗

PubMed1996

Review of theoretical passive drug absorption models: historical background, recent developments and limitations.

In the drug discovery process the optimization of a promising lead to an orally bioavailable drug remains a difficult task. Recent progress in the understanding of the role of physicochemical properties in membrane permeability relevant to important processes such as drug absorption and blood-brain barrier crossing, brings rational drug delivery more within reach. In the last thirty years a number of theoretical transport and absorption models have been developed to describe mathematically how a drug is being passively transported from its site of administration to its site of action and how a compound passes a membrane. The goal of such models is to rationalize the physical significance of the observed non-linear structure-permeability relationships. The models are based on various views on the composition of the biological membranes and on the underlying diffusion and distribution mechanisms. Often simplifications reducing the mathematical complexity are made. We review here a selection of the most important models and discuss modern views on the role of lipophilicity and various pathways through membranes.

Absorption↗

PubMed2002

Solvent gradient operation of simulated moving beds. I. Linear isotherms.

The simulated moving bed (SMB) is a multi-column chromatographic separation process, which--with respect to the single-column preparative batch process--allows for a continuous separation with larger productivity and smaller solvent consumption at the same time. The benefits of this process have been shown for several different applications in fine chemistry, particularly for the separation of enantiomers. In general, SMBs are operated under isocratic conditions. However, separation performance can be further improved by applying some sort of gradient mode operation, in order to optimize the operating conditions of each individual section of the unit. This can be achieved by tuning the retention behavior of the solutes to be separated along the unit, namely by enforcing weak adsorption conditions in sections 1 and 2, and strong adsorption conditions in sections 3 and 4. This can be achieved by applying a temperature gradient (high temperature in section 1, and low temperature in section 4), a pressure gradient (e.g. in the supercritical SMB, when pressure is high in section 1, and low in section 4), or a solvent gradient, which is the aim of this work. In the solvent gradient mode the mobile phase consists of a mixture of two or more solvents. To different mobile phase compositions corresponds a different retention behavior of the solutes, i.e. different adsorption isotherms. In this work we study a closed loop SMB unit with solvent mixtures of two different compositions entering the unit at the feed and desorbent inlet ports, respectively. Thereby two different mobile phase compositions are established in sections 1 and 2, and sections 3 and 4, respectively. To optimize this process the equilibrium theory design criteria for non-linear SMBs are extended to describe this operation mode. It is shown how the region of separation is derived and how the optimal operating conditions can be found. Finally the solvent gradient mode is compared with the isocratic mode in terms of productivity and solvent consumption.

Adsorption↗

PubMed2004

Controlled release of clozapine through chitosan microparticles prepared by a novel method.

A simple and commercially viable method of preparation of chitosan microparticles (MPs) was adopted for the entrapment of clozapine, which can be easily scaled-up to controlled drug delivery dosage form. This method is devoid of tedious processes like emulsification in oil phase, spray-drying, etc. MPs have been prepared by changing the experimental variables such as extent of crosslinking and amount of clozapine loading in order to optimize the process variables on the final percent drug entrapment efficiency, size of MPs and release rates. Absence of chemical interactions between drug, polymer and crosslinking agent after the production of MPs was confirmed by Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) spectra were obtained for clozapine-loaded chitosan MPs to understand the crystalline nature of the drug after entrapment. The results indicated a molecular level dispersion of clozapine in the polymer matrix. Effect of crosslinking and drug loading on thermal decomposition of chitosan was studied by thermogravimetry (TGA) and these data indicated that pure chitosan is stable when compared to clozapine-loaded chitosan. MPs produced were irregular in shape, with average particle sizes in the range of 543-698 microm as measured by the laser light scattering technique. Clozapine entrapment up to 98.97% was obtained as determined by high performance liquid chromatography. In vitro release studies were performed in phosphate buffer pH 7.4 solution and the release of clozapine was achieved up to 12 h. Swelling studies were conducted in water and diffusion coefficients (D) and diffusional exponents (n) for water transport were determined using the empirical equation. In vivo absorption kinetics of clozapine and clozapine-loaded MPs were investigated in albino rats. These results indicated that absorption of clozapine from MPs was delayed since the area under the curve was higher when compared to neat clozapine.

Animals↗

PubMed1989

Optimal fitting of computer model simulations to first transit cardiac radionuclide curves--II.

A discrete-time, lumped-parameter mathematical model of the human cardiopulmonary circulation as it appears during a first-transit radionuclide study has been described. An optimal fitting process is used to match curves obtained from the model to curves obtained from first transit studies in order to estimate the parameters of the subject's heart. The development of the optimization technique is described in this paper. The results of testing the effects of overlapping compartments and errors in delay estimates are presented. A parameter determination analysis is performed by applying the optimization algorithm to simulated data. This analysis technique provides a method of estimating many parameters of heart function using a single, simple, rapid procedure. Results of clinical studies will be presented subsequently.

Algorithms↗

PubMed2005

Prediction of segregation tendency occurrence in dry particulate pharmaceutical mixtures: development of a mathematical tool adapted for granular systems application.

Segregation phenomena are of importance in nearly all processes involving dry granular and powder mixtures. The extent of segregation directly influences the eventual rejection of a considerable percentage of the final product in the majority of pharmaceutical processes; among these are those mixtures destined for powder compression processing for the production of tablets. Although the parameters influencing segregation are relatively well-known qualitatively, there are, so far, no widely accepted quantitative prediction tools that permit process improvement and optimization of production as a function of the mixture's composition and the particulars of individual processes (e.g., geometry of the vessels). Thus, within present practice, only general design considerations and the technical expertise of engineers and operators are relied upon to optimize these processes on a case-by-case basis. It is in these circumstances that a study of the tendency towards segregation in free flowing granular materials was conducted, using a simple tool previously developed for the study of the behavior of continuous chemical reactors with classical fluid flows. The measurement of average residence times and their variance is used to calculate the deviation of chemical reactors from the ideal behavior of a perfectly mixed vessel or a plug flow pattern. In this work, these measurements are adapted to evaluate the tendency of a granular mixture to segregate. The method consists of introducing a pulse perturbation (of another material) to the established regular flow of a single granular material or a granular mixture and to then calculate the response of the system in terms of the concentration of the pulsed material at the process outlet. The average granular particle residence time and its standard deviation are then related to the segregation tendency.

Chemistry, Pharmaceutical↗

PubMed1997

Product quality and food processing: how to quantify the healthiness of a product.

This paper discusses possibilities to measure healthiness of a food product. It is argued that besides measurement of concentration of biologically active compounds it is also necessary to measure biological activity of such compounds in a food. In doing so, it becomes possible to substantiate health claims associated with a food, as well as to optimize food processing with respect to healthiness. Two examples are given of measuring bioactivity in a food, antioxidant activity of apple juice, and (anti)mutagenicity of heated milk. It is also stressed that optimization with respect to healthiness should be done taking other quality aspects (such as organoleptic properties, safety and nutritional value) into account.

Antimutagenic Agents↗