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PubMed2006

Effect of germination and thermal treatments on folates in rye.

Effects of germination conditions and thermal processes on folate contents of rye were investigated. Total folate contents were determined microbiologically with Lactobacillus rhamnosus (ATCC 7469) as the growth indicator organism, and individual folates were determined by high-performance liquid chromatography after affinity chromatographic purification. Germination increased the folate content by 1.7-3.8-fold, depending on germination temperature, with a maximum content of 250 micro g/100 g dry matter. Hypocotylar roots with their notably high folate concentrations (600-1180 micro g/100 g dry matter) contributed 30-50% of the folate contents of germinated grains. Germination altered the proportions of folates, increasing the proportion of 5-methyltetrahydrofolate and decreasing the proportion of formylated folate compounds. Thermal treatments (extrusion, autoclaving and puffing, and IR and toasting) resulted in significant folate losses. However, folate levels in grains that were germinated and then were heat processed were higher than for native (nongerminated) grains. Opportunities to optimize rye processing to enhance folate levels in rye-based foods are discussed.

Folic Acid↗

PubMed1999

Teaching fractional factorial experiments via course delegate designed experiments.

Industrial experiments are fundamental in enhancing the understanding and knowledge of a process and product behavior. Designed industrial experiments assist people in understanding, investigating, and improving their processes. The purpose of a designed experiment is to understand which factors might influence the process output and then to determine those factor settings that optimize the process output. Teaching "design of experiments" using textbook examples does not fully shed light on how to identify and formulate the problem, identify factors, and determine the performance of the physical experiment. Presented here is an example of how to teach fractional factorial experiments in a course on designed experiments. Also presented is a practical, hands-on experiment that has been found to be extremely successful in instilling confidence and motivation in course delegates. The experiment provides a great stimulus to the delegates for the application of experimental design in their own work environment.

Analysis of Variance↗

PubMed1978

Construct and ecological validity of short-term memory measures in retarded persons.

The performance of retarded subjects on five short-term memory tasks was analyzed in order to determine whether these tasks possessed construct and ecological validity. I predicted that certain components of each task required an active strategic process for optimal performance, whereas other components would only require a passive process. A principal axes factor analysis was performed on the intercorrelations of these components, and three factors were isolated that accounted for performance on the five tasks. Two of these factors were viewed as representing active and passive processes, and the third factor was determined by a recognition-memory task and, apparently, did not require the same processes as the recall tasks. These findings indicated that some of the short-term memory tasks possessed construct validity. An additional analysis was the investigation of the ecological validity of the various short-term memory tasks. Several multiple-correlation coefficients between memory scores and measures of adaptive behavior were significant and support the interpretation that the measures of short-term memory are ecologically valid.

Activities of Daily Living↗

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↗

PubMed2006

Modeling the partial nitrification in sequencing batch reactor for biomass adapted to high ammonia concentrations.

Partial nitrification has proven to be an economic way for treatment of industrial N-rich effluent, reducing oxygen and external COD requirements during nitrification/denitrification process. One of the key issues of this system is the intermediate nitrite accumulation stability. This work presents a control strategy and a modeling tool for maintaining nitrite build-up. Partial nitrification process has been carried out in a sequencing batch reactor at 30 degrees C, maintaining strong changing ammonia concentration in the reactor (sequencing feed). Stable nitrite accumulation has been obtained with the help of an on-line oxygen uptake rate (OUR)-based control system, with removal rate of 2 kg NH4 (+)-N x m(-3)/day and 90%-95% of conversion of ammonium into nitrite. A mathematical model, identified through the occurring biological reactions, is proposed to optimize the process (preventing nitrate production). Most of the kinetic parameters have been estimated from specific respirometric tests on biomass and validated on pilot-scale experiments of one-cycle duration. Comparison of dynamic data at different pH confirms that NH3 and NO2- should be considered as the true substrate of nitritation and nitratation, respectively. The proposed model represents major features: the inhibition of ammonia-oxidizing bacteria by its substrate (NH3) and product (HNO2), the inhibition of nitrite-oxidizing bacteria by free ammonia (NH3), the INFluence of pH. It appears that the model correctly describes the short-term dynamics of nitrogenous compounds in SBR, when both ammonia oxidizers and nitrite oxidizers are present and active in the reactor. The model proposed represents a useful tool for process design and optimization.

Adaptation, Physiological↗

PubMed1990

[Digital mammography is very useful in mass screening of breast cancer].

Mammograms made between 1981 and 1989 in the Nijmegen screening programme for breast cancer were retrospectively reviewed. Those made before detection of breast cancer showed signs of tumour growth in the place of the subsequently detected malignancy in 22% of the cases. A work station was set up for image digitization and image processing. Display with optimal contrast and image processing of mammograms is possible. Diagnoses based on digitized mammograms displayed on a monitor were as good as those based on the conventional images on film. Automatic detection of image features has been investigated. A procedure for automatic detection of microcalcifications was developed. This research is important for optimalization of diagnosis in screening and because of the expected introduction of direct digital imaging techniques.

Breast Neoplasms↗

PubMedDate not supplied

Optimization of the drug solution preparation process for a production-scale crossflow ultrafiltration system.

This article describes a new approach to optimizing the drug solution preparation process for a production-scale crossflow ultrafiltration system. Equations were proposed to predict the concentration of the active ingredient and the volume of drug solution in the crossflow ultrafiltration process. These equations take into account the residual water remaining in the process line after the set-up of the ultrafiltration system, the residual drug solution remaining in the process line after ultrafiltration, and the residual Water for Injection (WFI) remaining in the process line after WFI rinsing. Because the residual water or residual drug solution varies slightly for each type of production, it was convenient to define them as preparation parameters. Using the proposed equations, testing was performed during early production in order to collect data on the crossflow ultrafiltration process, and the preparation parameters were then optimized. The concentration of the active ingredient and the weight of the drug solution (which was converted to the drug solution volume using its specific gravity) were calculated accurately with the optimized preparation parameter using the proposed equations. These results indicate that the proposed equations and method of establishing the preparation parameters are useful for a production-scale crossflow ultrafiltration system.

Algorithms↗

PubMed2005

Valence electron energy-loss spectroscopy in monochromated scanning transmission electron microscopy.

With the development of monochromators for (scanning) transmission electron microscopes, valence electron energy-loss spectroscopy (VEELS) is developing into a unique technique to study the band structure and optical properties of nanoscale materials. This article discusses practical aspects of spatially resolved VEELS performed in scanning transmission mode and the alignments necessary to achieve the current optimum performance of approximately 0.15 eV energy resolution with an electron probe size of approximately 1 nm. In particular, a collection of basic concepts concerning the acquisition process, the optimization of the energy resolution, the spatial resolution and the data processing are provided. A brief study of planar defects in a Y(1)Ba(2)Cu(3)O(7-)(delta) high-temperature superconductor illustrates these concepts and shows what kind of information can be accessed by VEELS.

Journal Article↗

PubMed2006

Effect of single-point sequence alterations on the aggregation propensity of a model protein.

Sequences of contemporary proteins are believed to have evolved through a process that optimized their overall fitness, including their resistance to deleterious aggregation. Biotechnological processing may expose therapeutic proteins to conditions that are much more conducive to aggregation than those encountered in a cellular environment. An important task of protein engineering is to identify alternative sequences that would protect proteins when processed at high concentrations without altering their native structure associated with specific biological function. Our computational studies exploit parallel tempering simulations of coarse-grained model proteins to demonstrate that isolated amino acid residue substitutions can result in significant changes in the aggregation resistance of the protein in a crowded environment while retaining protein structure in isolation. A thermodynamic analysis of protein clusters subject to competing processes of folding and association shows that moderate mutations can produce effects similar to those caused by changes in system conditions, including temperature, concentration, and solvent composition, that affect the aggregation propensity. The range of conditions where a protein can resist aggregation can therefore be tuned by sequence alterations, although the protein generally may retain its generic ability for aggregation.

Amino Acid Substitution↗

PubMed2004

Novel buffer systems for macromolecular crystallization.

In protein crystallization, screening is initially performed to obtain an indication of the conditions under which a macromolecule might crystallize. These preliminary conditions are then optimized to produce (in a perfect world) well diffracting crystals; this process of optimization often involves fine grid screening around the initial conditions. An issue in optimization is to find factors which are independent, so as to simplify the analysis of the results of optimization trials. This is necessarily difficult with buffers, as a buffer and its pH range tend to be very highly correlated. Multi-buffer systems for pH modulation are presented which enable a broad pH range to be sampled without changing the chemical composition of the buffering component.

Buffers↗

PubMed2006

Optimization of an innovative hollow-fiber process to produce lactose-reduced skim milk.

The research field for applications of lactose hydrolysis has been investigated for several decades. Lactose intolerance, improvement for technical processing of solutions containing lactose, and utilization of lactose in whey are the main topics for development of biotechnological processes. We report here the optimization of a hollow-fiber membrane reactor process for enzymatic lactose hydrolysis. Lactase was circulated abluminally during luminal flow of skim milk. The main problem, the growth of microorganisms in the enzyme solution, was minimized by sterile filtration, ultraviolet irradiation, and temperature adjustment. Based on previous experiments at 23 +/- 2 degrees C, further characterization was carried out at 8 +/- 2 degrees C, 15 +/- 2 degrees C (beta-galactosidase), and 58 +/- 2 degrees C (thermostable beta-glycosidase) varying enzyme activity and flow rates. For a cost-effective process, the parameters 15 +/- 2 degrees C, 240 U/mL of beta-galactosidase, an enzyme solution flow rate of 25 L/h, and a skim milk flow rate of about 9 L/h should be used in order to achieve an aimed productivity of 360 g/(L x h) and to run at conditions for the highest process long-term stability.

Animals↗

PubMed2006

Practical approach to parameter estimation for ASM3+ bio-P module applied to five-stage step-feed EBPR process.

Various parameter optimization approaches to a five-stage step-feed EBPR process modeled using the ASM3+bio-P module were examined. Five stoichiometric (Y(STO,NO), Y(H,O2, Y(H,NO,) Y(PAO,O2), Y(PO4)) and seven kinetic parameters (k(STO), eta(NO), b(H), mu(max),PAO, q(PHA), q(PP), mu(max),A) were estimated. The optimization approaches could be classified based on the data sources (batch experiments or CSTR operation data) and the number of target variables used in calculating the objective function. Optimized parameter values obtained by each approach were validated with CSTR operation data that were not used for parameter optimization. The results showed that the parameter optimization only with batch experimental results could not be directly applied to CSTR operation data. ASM3 + bio-P module parameters could be finely optimized only with CSTR operation data when sufficient target variables for objective function calculation were applied. When the number of target variables was increased, prediction performance was significantly improved. Once optimized, the model was able to predict the characteristic features of the five-stage step-feed process; namely, a high PAO yield, fast PAO growth, fast X(pp) storage, slow X(STO) and X(PHA) storage.

Bioreactors↗

PubMed1994

Suboptimal control of fed-batch bioprocesses using phase properties.

A new method for the evaluation of suboptimal feeding strategies for fed-batch bioprocesses is introduced. This method is based on a time-local optimization of the process dynamics. To include global effects into the optimization, the process has to be partitioned into several phases with different local extremality conditions. The penicillin bioprocess is used to illustrate the method. One advantage of the proposed method is that the evaluated control function appears as a feedback law. Simultaneously, the new method allows the inclusion of constraints on the process states and the use of very complex models. Due to the simplicity and stability of the numerical procedure the method is robust against external perturbation. Therefore, it is suited for use in on-line controls.

Algorithms↗

PubMed2004

Delineating bone's interstitial fluid pathway in vivo.

Although interstitial fluid flow has been suggested to play a role in bone adaptation and metabolism, the constituents and ultrastructure of this interstitial fluid pathway are not well understood. Bone's lacunar-canalicular porosity is generally believed to be a continuous interstitial fluid pathway through which osteocytes sense external mechanical loading as well as obtain nutrients and dispose of wastes. Recent electron microscopy studies have suggested that a fiber matrix surrounds the osteocytic cell processes and fills this pericellular fluid space. However, studies injecting tracer molecules into the bone vasculature have provided conflicting results about the pore size or the fiber spacing of the interstitial fluid pathway. In addition, whether the smaller collagen-apatite porosity in adult bone is also a continuous fluid pathway is still unclear. To delineate bone's interstitial fluid pathway, four tracers of various size were injected into rats: reactive red (approximately 1 nm), microperoxidase (MP, approximately 2 nm), horseradish peroxidase (HRP, approximately 6 nm), and ferritin (approximately 10 nm). Five minutes after injection, the tibiae were harvested and processed using histological protocols optimized to minimize processing time to reduce possible redistribution of tracer molecules. The number of blood vessels and osteocytic lacunae labeled with the tracers per unit bone area was then measured for mid-diaphysial cross-sections of the tibia. While none of the tracers was detected within the mineralized bone matrix (the collagen-apatite porosity) using light microscopy, all the tracers except ferritin were found to pass through the canaliculi and appear in the osteocytic lacunae. These results indicate that while small tracers (<6 nm) readily pass through the lacunar-canalicular porosity in the absence of mechanical loading, there appears to be an upper limit or cutoff size between 6 and 10 nm for molecular movement from bone capillaries to osteocytic lacunae in rat long bone. This range of pore size contains the most likely fiber spacing (approximately 7 nm) that has been proposed for the lacunar-canalicular annular space based on the presence of a proteoglycan fiber matrix surrounding the osteocyte.

Animals↗

PubMed2004

Glass encapsulation of flavours with chemically modified starch blends.

Carrier compositions based on blends of various octenylsuccinic acid anhydride (OSAN)-modified starches were utilized in the glass encapsulation of flavours by means of melt extrusion and spray drying. Dextrinized, acid and enzymatically hydrolysed OSAN starches were used in various combinations. Processing parameters were optimized for desirable physical chemical and functional properties of the encapsulating compositions. One key property in the optimization of the extrusion process was setting rate of the exiting melt into a glass. Glassy states of identical spray-dried and extruded compositions were characterized by MDSC for glass transition temperature(s), heat capacity change and enthalpy relaxation. Flavour retention, surface flavour, moisture, particle density and flavour particle size distribution were also measured and compared for the extruded and spray-dried compositions. In addition, elastic recovery and caking were evaluated for extruded compositions. The glass transition parameters were correlated directly or indirectly with most of the physical properties of encapsulating compositions, especially flavour retention, surface flavour and caking. In extruded compositions, two phases were revealed by the presence of two glass transitions, whereas spray-dried compositions showed only one broad glass transition.

Drug Compounding↗

PubMed2004

Efficiency optimization for systems and components in microwave power engineering.

The paper is concerned with one aspect of optimization of microwave thermal processing, namely, with optimization of energy coupling interpreted as a numerical characteristic of system efficiency. Since in computer-aided design coupling can be evaluated through the computed reflections, an optimization scheme is presented that is particularly suitable for minimizing the reflection coefficient in typical systems and elements of microwave power engineering. Based on response surface methodology and the sequential quadratic programming for constrained optimization, the procedure is linked with the full-wave 3-D FDTD electromagnetic simulator QuickWave-3D. Credibility and effectiveness of the method is illustrated by four examples: dimensional optimization is performed for a dry waveguide load, a waveguide T-junction with a partial-height post, a water cylinder in a cavity, and a slotted waveguide-backed radiating element.

Journal Article↗

PubMed2006

Manufacture, characterization, and pharmacodynamic evaluation of engineered ipratropium bromide particles.

PURPOSE: The intent of this research was to generate and characterize respirable particles of ipratropium bromide (IPB), a short-acting anticholinergic bronchodilator, to achieve demonstrable sustained-release properties. The value of a long-acting anticholinergic agent is evident in the use of tiotropium for the treatment of chronic obstructive pulmonary disease. METHODS: Hollow, spherical particles of ipratropium bromide suitable for inhalation were generated using a spray-drying process and characterized by laser diffraction particle size analysis, scanning electron microscopy, dynamic vapor sorption, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and dissolution testing. Experimental design techniques were used to identify critical process parameters and optimize the spray drying process. Pharmacodynamic studies were conducted to determine duration of effect. RESULTS: Crystalline, stable, respirable particles with a range of dissolution profiles were manufactured by application of polylactic acid (PLA) coatings of 1, 5, 10, 15, 30, and 50% w/w. A novel, robust, modified Type IV dissolution method discriminated between formulations and guided their development. Preliminary studies in guinea pigs indicated an increased duration of bronchodilatory effect for 30% PLA-coated particles (56.3 min) particles compared with IPB powders alone (11.0 min). CONCLUSIONS: Sustained-release respirable particles of ipratropium bromide were developed using a PLA spray coating approach and a trend for increased duration of effect was demonstrated in guinea pigs.

1,2-Dipalmitoylphosphatidylcholine↗

PubMed2003

Beam orientation optimization for IMRT by a hybrid method of the genetic algorithm and the simulated dynamics.

We have developed a new method for beam orientation optimization in intensity-modulated radiation therapy (IMRT). The problem of beam orientation optimization in IMRT is solved by a decoupled two-step iterative process: (1) optimization of the intensity profiles for given beam configurations; (2) selection of optimal beam configurations based on the ranking by an objective function score for the results of the intensity profile optimization. The simulated dynamics algorithm is used for the intensity profile optimization. This algorithm enforces both the hard constraints and dose-volume constraints. A genetic algorithm is used to select beam orientation configurations. The method has been tested for both a simulated and clinical case, and the results show that beam orientation optimization significantly improved IMRT plans within a time period that is clinically acceptable. The results also show the dependence of the optimal orientation configurations on the prescribed constraints. In addition, beam orientation optimization by the method described here can provide multiple plans with similar dose distributions. This degeneracy characteristic can be exploited to our advantage in introducing additional planning objectives, e.g., the smoothness of intensity profiles, for the selection of the optimal plan among the degenerate configurations for treatment delivery.

Algorithms↗