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Continuous purification of a clotting factor IX concentrate and continuous regeneration by preparative annular chromatography.

Preparative continuous annular chromatography, a method to separate proteins in a truly continuous manner, was investigated in an industrial environment. Plasma-derived clotting factor IX concentrate was used as model protein. Separation of vitronectin, a common impurity in commercial available factor IX concentrates, from factor IX was studied and compared to conventional packed bed chromatography in batch mode. As sorbent, Toyopearl DEAE 650M was used. Regeneration was performed simultaneously with the purification of factor IX in continuous mode. All required parameters applied for preparative annular chromatography such as feed flow-rate and elution flow-rate were first estimated from experiments on conventional batch columns. Then preparative annular chromatography and conventional packed beds were compared regarding enrichment, purity and productivity. Three different process scenarios, the optimal batch process,the preparative annular chromatography process and the batch process equivalent to the preparative annular chromatography process were investigated. The productivity of the optimal batch process was higher than that of the preparative annular chromatography and batch process equivalent to the preparative annular chromatography process. Therefore the throughput could not be increased by the use of the continuous chromatographic system.

Blotting, Western↗

A neural network strategy for end-point optimization of batch processes.

The traditional way of operating batch processes has been to utilize an open-loop "golden recipe". However, there can be substantial batch to batch variation in process conditions and this open-loop strategy can lead to non-optimal operation. In this paper, a new approach is presented for end-point optimization of batch processes by utilizing neural networks. This strategy involves the training of two neural networks; one to predict switching times and the other to predict the input profile in the singular region. This approach alleviates the computational problems associated with the classical Pontryagin's approach and the nonlinear programming approach. The efficacy of this scheme is illustrated via simulation of a fed-batch fermentation.

Algorithms↗

Methods and strategies available for the process control and optimization of monoclonal antibody production.

The objective of this paper is to explore the range of methods and strategies available for the process control and optimization of monoclonal antibody production by hybridoma cell culture. Emphasis will be placed on the choice of the level of complexity incorporated into the process control and optimisation procedure. It will be shown that the behaviour of hybridomas in culture is influenced by sophisticated cellular metabolic activities and various interactive environmental factors and that the understanding and modelling of the way hybridomas grow in the bioreactor should enable optimisation of bioreactor operating conditions to achieve maximum monoclonal antibody formation. However, due to the lack of on-line instrumentation of important biological variables and the incomplete knowledge of hybridoma cultivation process, there exist many limitations and challenges to the advent of applications of process control and optimisation in this field. To solve the problem, introduction of industrially practical biological measurements and development of new control concepts are inevitable. At the end of this paper, we shall discuss possible schemes for the control of the physiological state of cells in order that balanced cell growth and maximum monoclonal antibody synthesis may be achieved.

Animals↗

[Practical games as one of the forms for optimizing the academic process in physician postgraduate training].

Described in the article is one of the forms of optimization of the instructional process in the postgraduation physician training--"business-like games". Highly skilled, competent position of the teacher who conducts a business-like game secures an active participation in learning of students, helps in opening the mind, broadening the outlook on the problem under consideration, gives much incentive to further independent work on the discussed issues.

Diagnosis, Differential↗

Process evaluation for optimization of EDTA use and recovery for heavy metal removal from a contaminated soil.

This study aimed to establish an optimized, closed loop application of ethylenediaminetetraacetic acid (EDTA) in heavy metal removals from a contaminated soil through integrating EDTA recovery/regeneration and metal precipitation processes in the treatment train. Three divalent heavy metals were investigated, namely, Pb, Cd, and Ni. The extractability of the metals by EDTA followed the decreasing order of CdPb>>Ni. The first part of this study was to search for the optimal use of the fresh EDTA in removing these heavy metals from the contaminated soil. The second part of this study was devoted to the recovery/regeneration of the spent EDTA which followed the sequential processes involving (1) complex destabilization by adding ferric ion (Fe(III)) to liberate Pb, Cd, and Ni, (2) precipitation of the liberated Pb, Cd, and Ni in phosphate (PO4(3-)) forms, and (3) precipitation of the excess Fe(III) which eventually produced free EDTA for reuse. The process variables were dosages of Fe(III) and PO4(3-), pH and reaction times. Laborious trial experiments would be needed in searching for the optimum conditions for the above processes. To expedite this exercise, a geochemical equilibrium model, MINTEQA2, was used to find the thermodynamically favorable conditions for recoveries of both EDTA and heavy metals. This was then followed by experimental examination of the process kinetics to observe for the optimal reaction time for each thermodynamically favorable process. This study revealed that 2 h of reaction time each for the complex destabilization reaction and the metal phosphate precipitation reaction was sufficient to achieve equilibrium. With the optimized process condition identified in this study, a total of 95%, 89% and 90% of the extracted Pb, Cd and Ni, respectively, could be precipitated from the spent EDTA solution, with 84% EDTA recovery. The reused EDTA maintained more than 90% of its preceding extraction power in each cycle of reuse.

Chelating Agents↗

[Study on extraction process of the volatile oil for biyuan dropping pills].

OBJECTIVE: To determine the optimal extracting process of the volatile oil for Biyuan Dropping Pills. METHODS: Conditions for the extraction were studied by orthogonal design guided by the increasement of the volatile oil. RESULTS: The distilling time is the main factor,and the fineness of the herbal material is the second. The optimal process is as follows: crush the herbal material into coarse powder, macerate 1 hour with 9 times water and distill 4 hours. CONCLUSION: The optimized process is feasible and stable.

Analysis of Variance↗

The role of social cognitive processing theory and optimism in positive psychosocial and physical behavior change after cancer diagnosis and treatment.

The physical and psychosocial 'health' behaviors of cancer patients have become a more pressing issue as 5-year survival rates continue to rise. This study investigated: (a) the extent of positive change in four psychosocial behaviors and two physical health behaviors, (b) the role of psychosocial predictors (drawn from theories of Social Cognitive Processing and optimism) in positive behavior change after cancer diagnosis and treatment, and (c) the possible influence of social desirability in reports of positive psychosocial and physical behavior change. The behavior showing the greatest positive change was time spent reflecting on life priorities; the behavior that was least likely to change after diagnosis and treatment was exercise. Optimism, social support, and cancer-related intrusions were positively associated with increases in physical health behaviors. Only optimism was positively associated with increases in psychosocial behaviors. Reports of positive change in physical and psychosocial behaviors were only modestly correlated. Social desirability was unrelated to reports of positive behavior change. Results are interpreted in light of theories of adaptation to cancer diagnosis and treatment.

Adaptation, Psychological↗

[Evaluation of commercial UHT milk and optimization of industrial process].

From the nutrition al point of view milk is one of the most complete food in the diet of mammals. It contains nearly all the nutrients necessary to sustain life, but milk can deteriorate very easily, either by microbiological contamination or by biochemical reactions during processing and/or storage. The objective of this research study was to design a modified UHT treatment to achieve commercial sterilization and maximize the stabilization of the heat-treated product during storage. To search for a modified UHT process, a mathematical model coupled with an optimization routine (complex method) was developed. The mathematical model considers Kinetics for the inactivation of Bacillus stearothermophilus and several quality factors. To attain the objective function, several commercial UHT milk were analyzed and for the computer search the minimization of hydroxy methyl furfural (HMF) formation was considered and also including constraints for protease and lipase inactivation. The complex optimization procedure was implemented to search for the optimum modified UHT treatment.. One of the optimum modified UHT treatments was the combination of two pre-treatment (3.16 minutes at 62.30 degrees C and 6 minutes at 75 degrees C) in addition with a UHT treatment (0.75 s at 148.8 degrees C). This treatment attains the maximum product stability with a negligible effect on composition and color formation in the treated milk (HMF formation less than 3 mg/mL).

Animals↗

Microencapsulation of a hydrophilic drug into a hydrophobic matrix using a salting-out procedure. I: Development and optimization of the process using factorial design.

The congealable disperse phase method for preparing sustained release microspheres involves an emulsification process using water as the external phase and molten hydrophobic wax as the disperse phase into which the drug is loaded. Attempts to entrap highly water-soluble drugs using this process have often resulted in low loading efficiency as the drugs partition into the external water phase during emulsification and are lost. A novel method employing salts and wetting agents was developed to improve the loading efficiency of the highly water-soluble drug, guaifenesin, using this method. The drug/wax ratio (D/W) and the presence of salts and wetting agents greatly influenced microsphere properties. To optimize the process for drug loading efficiency and release rate, three different D/Ws, salts and wetting agents were chosen and a full 3(3) factorial design experiment was performed. Any significant differences among the levels of the variables and their individual and joint effects on entrapment efficiency and T50 (time for 50% drug release) were determined. Entrapment efficiencies in the range 35.1-86.3% were obtained for the various factor-level combinations of the variables. Particle size was in the range 140-385 microm and T50 was 0.59-2.72 h for the microspheres obtained. The D/W and type of salt used significantly affected drug entrapment and T50, while the nature of wetting agent was not significant at p < 0.05. The microspheres prepared using 1:4 D/W showed the highest entrapment efficiency and slowest drug release.

Delayed-Action Preparations↗

[Optimizing the nursing process by new management instruments. The Northern Germany Nursing Research Network].

The Northern Germany Nursing Research Network (Pflegeforschungsverbund Nord) has dedicated itself to developing management instruments intended to optimize the nursing process. It is coordinated by the administrative office of the Institute of Public Health and Nursing Research (Institut für Public Health und Pflegeforschung IPP, director: Prof. Dr. Stefan Görres), Department of "Interdisziplinäre Alterns- und Pflegeforschung", University of Bremen. Four partial projects are currently being worked on in two groups: Group A--"Deficient areas of nursing action": The projects belonging to this group are "Individual care-patterns of elderly people and their determinants" (University of Bremen) and "Mobility Restrictions in Nursing Homes-Multicentre Observational Study (MORIN)" (University of Hamburg). The purpose of these studies is to examine the relevance of quantitatively significant risk combinations from a nursing science perspective. Group B--"The generation and testing of nursing action management instruments": The projects in this area are "Nursing rounds as instruments of quality assurance in home-based care" (University of Applied Sciences, Bremen) and "Predicting the risk of falls, efficiency of standard scales in opposition to nursing assessment-Cluster-Randomised Controlled Trial (PROFESSION)" (University of Hamburg). These studies concentrate in a unique manner on the generation and testing of management/control instruments suitable for application to nursing action.

Activities of Daily Living↗

Optimization of the granulation process for designing tablets.

A computer optimization technique based on surface response methodology was applied to optimize the wet granulation process for designing tablets. Physical properties (mean granule size, granule size distribution, compressibility, granule strength) of a model granule formulation containing ethenzamide were accurately described by a second polynomial equation based on two independent variables (amounts of binder and binder solution). This regression equation also gave a good correlation for three physical properties of tablets (distintegration time, compactibility, compression force variance), but the correlation for tablet hardness and weight variation was poor. These results imply that not only the above physical properties of granules but also the rheological behavior and porous structure of granules are closely related to tablet properties. Using an optimization of five tablet properties using the generalized distance function, the predicted values of the physical properties of both granules and tablets agreed well with experimental values. This agreement indicates that the computer optimization technique is useful for optimizing the granulation process for designing tablets.

Computers↗

Age related preservation and loss in optimized brain SPECT.

BACKGROUND: Recent single photon emission computed tomography (SPECT) studies have reported age related increases in regional brain perfusion (called preservation here) as well as losses. AIM: To apply optimized SPECT processing to better define and understand both age related preservation and loss in brain SPECT. METHODS: Brain SPECT was performed on 85 healthy subjects using Tc hexamethylpropylene amine oxime (HMPAO), processed using findings from recent optimization work, and subjected to voxel based statistical analysis. RESULTS: SPECT preservation was seen in white matter. This distribution differs from other SPECT reports, but is similar to that for preservation observed with structural magnetic resonance imaging (MRI). This suggests that SPECT preservation may arise from age related changes in brain anatomy, not regional cerebral blood flow (rCBF), and we demonstrate that it can arise from the partial-volume effect in areas where white matter contracts with age. Age related losses extended over the whole pre-frontal midline area and an extended pattern of focal losses was seen in the peripheral cortex that was consistent with major sulci. There were also focal losses in the cerebellum. The most significant SPECT loss was in the anterior cingulate, although no structural changes were observed there in the MRI study. A model of sulcal widening at the junction of the inter-hemispheric fissure and cingulate sulcus, when degraded by the partial-volume effect, could explain this anterior cingulate loss. CONCLUSION: Optimized processing has revealed spatial patterns for age related preservation and losses in brain SPECT that indicate their origin is primarily structural. Correction for structural effects in optimized SPECT is needed to confirm whether any regional ageing effects derive from changes in rCBF.

Adolescent↗

[Optimization of the process of larval development in the housefly as a utilizer of organic wastes in a human biological life support system].

The development of Musca domestica L. larvae as utilizers of organic wastes in the biological life support system was investigated by methods of mathematical planning. The optimization of the process under study is based on the reduction to the canonical form of regression models set by second order polynomials. This approach was tested when determining optimal conditions for larval development and substrate utilization with respect to 5 factors. On the basis of optimization results the following parameters were selected to ensure effective utilization of the substrate by larvae: the amount of substrate--150 g, its height--2.0 cm, temperature--34-35 degrees, humidity--77%, larval density--10 larvae per g wet substrate.

Animals↗

Application of model discriminating experimental design for modeling and development of a fermentative fed-batch L-valine production process.

A model discriminating experimental design approach for fed-batch processes has been developed and applied to the fermentative production of L-valine by a genetically modified Corynebacterium glutamicum strain possessing multiple auxotrophies as an example. Being faced with the typical situation of uncertain model information based on preliminary experiments, model discriminating design was successfully applied to improve discrimination between five competing models. Within the same modeling and experimental design framework, also the planning of an optimized production process with respect to the total volumetric productivity is shown. Simulation results were experimentally affirmed, yielding an increased total volumetric productivity of 6.2 mM L-valine per hour. However, also so far unknown metabolic mechanisms were observed in the optimized process, underlining the importance of process optimization during modeling to avoid problems of extreme extrapolation of model predictions during the final process optimization.

Biotechnology↗

Optimizing ammonia pressurization/depressurization processing conditions to enhance enzymatic susceptibility of dwarf elephant grass.

An ammonia pressurization/depressurization process was investigated to evaluate the potential of producing reducing sugars from dwarf elephant grass, a warm-season forage. Moisture, temperature, and ammonia loading affected sugar yield (p < 0.0001). At optimal conditions, ammonia processing solubilized 50.9% of the hemicellulose and raised the sugar yield (percentage of theoretical) from 18 to 83%. Glucose and xylose production were increased 3.2- and 8.2-fold, respectively. The mild processing conditions of the ammonia treatment (90-100 degrees C, 5 min), the low enzyme loading (2 international filter paper units/g), and the short hydrolysis time (24 h), greatly enhance the potential of using forages to produce sugars valuable for several applications.

Ammonia↗

Optimal protocol for processing high-volume and Peds Plus blood cultures by the BACTEC NR860.

The optimal incubation period for blood cultures collected in high-volume (Plus 26) and anaerobic (NR7A) media or Peds Plus medium and processed by the BACTEC NR860 was evaluated during a 12-month period. Organisms were recovered from 9% (1528 of 16,870) of blood culture vials (14% [1302 of 9118] of sets). Ninety-eight percent of positive vials were detected by day 5. Thirty-three vials (Plus 26 or NR7A) became positive on day 6 or 7; all positive Peds Plus vials were detected by day 5. Therapy did not change in response to detection of the organisms (26 "occasional" pathogens, 9 "usual" pathogens) in these vials. One usual pathogen had potential clinical significance, but the patient from whom the culture was collected died before it became positive. In the author's institution, the 5-day protocol for processing blood cultures could be adopted without compromising patient care.

Bacteremia↗

Optimal temperature control policy for a two-stage recombinant fermentation process.

The optimal temperature control policy to be followed in the operation of a two-stage fermentation system in which gene expression is induced by a temperature-sensitive gene switching system was studied. A genetically structured model was used to describe product formation, and kinetic equations based on experimental data were used to quantify the specific gene expression rate and parameters that affect plasmid instability. A constant temperature control policy and temperature profiling control policy including temperature cycling were studied and compared. Maximum average production rate was obtained from a temperature control policy in which the second stage was operated initially at about 40.5 degrees C and the temperature decreased slightly to a constant value at 40.0 degrees C. The maximum average production rate, which corresponds to the optimal temperature control policy, for an operation of 180 h was 29.7 units of protein (mg of cells)-1 h-1.

DNA, Recombinant↗

Optimization of the processing of matrix pellets based on the combination of waxes and starch using experimental design.

An experimental design was used in order to optimize the one-step production process of matrix pellets based on the combination of waxes and starch. The parameters tested were the impeller speed (x1) and the mixing time (x2). Ibuprofen and theophylline were used as model drugs at a concentration of 60 and 70% (w/w), respectively. The 0.8-1.25 mm yield fraction of the matrix pellets was evaluated as the response factor Y. A quadratic equation was fitted to the experimental data and used to predict the response factor Y of the theophylline and the ibuprofen. The contour plots of both formulations revealed a flat and therefore rugged region from the upper left to the lower right of the domain investigated. The energy input into the system during the production process controlled the pellet growth, the impeller speed having a greater impact on the energy input compared to the mixing time.

Delayed-Action Preparations↗