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Priming and the predictability of contextual information.

Past research has indicated that repetition priming is disrupted by variable contextual information such as word-to-word changes in voice. In three experiments, we examined whether subjects' prediction of contextual changes could attenuate this effect. Predictability of contextual changes was accomplished either by presenting speakers' voices in a fixed sequential order or by giving subjects prior knowledge of which voice would produce the next word. In these experiments, predictability attenuated the disruptive effect that changes in voice had on priming, suggesting the processes which underlie this memory phenomenon are modulated by expectations that selectively optimize subjects' processing of incoming information.

Adolescent↗

Carboxyl-terminal processing of the D1 protein and photoactivation of water-splitting in photosystem II. Partial purification and characterization of the processing enzyme from Scenedesmus obliquus and Pisum sativum.

The D1 polypeptide of photosystem II (PSII) is synthesized as a precursor that is processed by cleavage at the carboxyl terminus during assembly of the active PSII complex. A mutant of the green alga Scenedesmus obliquus, LF-1, inactive in water-splitting, lacks the D1 processing activity but assembles otherwise normal PSII complexes containing the precursor D1 molecule. We have isolated and partially purified a soluble protease from sonicated thylakoids of both wild-type S. obliquus and Pisum sativum which will process the precursor D1 molecule in PSII-enriched membranes from the LF-1 mutant to the mature size. After processing (but not before), photoactivation of these PSII membranes in the presence of manganese restores water-splitting to levels seen after photoactivation of PSII membranes from dark-grown, wild-type, cells. The protease is unable to process D1 in intact thylakoids from the LF-1 mutant but processes D1 if present during sonication of the thylakoids, indicating that processing of the carboxyl-terminal extension of D1 occurs in the lumen of the thylakoid. The processing protease from both S. obliquus and P. sativum is a single subunit enzyme of native molecular mass 33-35 kDa. Processing rate is optimal at pH 6.5. Processing in vitro is evident within 5 min and is markedly inhibited by millimolar concentrations of divalent cations (Cu, Zn greater than Mn greater than Ca, Mg) but not by any known inhibitors of the major classes of proteases. The protease is inactive against the precursors of other thylakoidal proteins and is thus distinct from the thylakoidal amino-terminal processing enzyme involved in the removal of transit peptides from cytoplasmically-synthesised proteins imported into the thylakoid lumen.

Algal Proteins↗

High throughput electrophysiology using a fully automated, multiplexed recording system.

The drug discovery process centers around finding and optimizing novel compounds active at therapeutic targets. This process involves direct and indirect measures of how compounds affect the behavior of the target in question. The sheer number of compounds that must be tested poses problems for classes of ion channel targets for which direct functional measurements (e.g., traditional patch-clamping) are too cumbersome and indirect measurements (e.g., Ca(2+)-sensitive dyes) lack sufficient sensitivity or require unacceptable compromises. We present an optimized process for obtaining large numbers of direct electrophysiological measurements (two-electrode voltage-clamp) from Xenopus oocytes using a combination of automated oocyte handling, efficient and flexible liquid delivery, parallel operation, and powerful integrated data analysis. These improvements have had a marked impact, increasing the contribution electrophysiology makes in optimizing lead compound series and the discovery of new ones. The design of the system is detailed along with examples of data generated in support of lead optimization and discovery.

Animals↗

Greener by design.

Process simulation models and other design tools allow engineers to design, simulate, and optimize chemical processes. However, there is a critical need to incorporate green engineering into the design of these processes. This calls for extending the breadth of the design process. This paper presents an integrated framework for greener design. The framework starts the decision-making as early as the chemical and material selection stage and also includes management and planning decisions. The design goal is not restricted to profitability, but environmental and ecological objectives are also added. However, this integration poses challenging problem of discrete and continuous decisions, nonlinear models, and uncertainties. Furthermore, there are multiple and conflicting objectives to be considered. Therefore, the core of this integrated framework is the efficient algorithmic framework for multiobjective optimization under uncertainty. Two real world case studies are presented that illustrate the promise of such a framework.

Algorithms↗

Development of probiotic cheese manufactured from goat milk: response surface analysis via technological manipulation.

Production of caprine milk has been rising steadily, partially because of its good nutritional value; the possibility of improving nutritional benefits by adding probiotic species such as Bifidobacterium lactis and Lactobacillus acidophilus was assessed. The manufacturing process of a traditional semi-hard goat cheese was technologically modified to optimize the process. The amount of starter inoculum, the concentration of salt, the addition of a protein hydrolysate, and the ripening time were varied to improve the microbiological, biochemical, and sensory properties of the cheese. Bifidobacterium lactis was able to grow slightly (up to 3 x 10(8) cfu/g), but growth was dependent on the physicochemical characteristics of the cheese. Lactobacillus acidophilus did not grow substantially in any of the experimental cheeses, and maximum numbers did not exceed 6 x 10(7) cfu/g. Concentrations of lactic acid and acetic acid increased throughout cheese manufacture, indicating that production of these acids was uncoupled from growth. Viability of the probiotic strains during ripening was sufficient to yield numbers that were above the accepted threshold (10(6) cfu/g) for a probiotic effect. Both strains contributed significantly to ripening, especially in the formation of low molecular mass peptides and amino acids, but lipolysis was not greatly affected. Statistical analyses using response surface methodology indicated that the manufacture of goat cheese could be optimized by the addition of 0.30% (vol/wt) milk hydrolysate, 3 x 10(7) of viable B. lactis and 7 x 10(6) of viable L. acidophilus cells/ml of milk, respectively, 3.50% (wt/wt) salt, and ripening for 70 d.

Acetic Acid↗

A laboratory evaluation of four quality control devices for radiographic processing.

Quality assurance programmes for radiographic processing traditionally employ expensive sensitometric and densitometric techniques. However cheap and simple devices for monitoring radiographic processing are available. The aim of this study was to make a comparison of four such devices in terms of their ability to detect variations in radiographic density of clinical significance. Three of the devices are commercially available while the fourth is easily manufactured from waste materials. Ideal bitewing exposure times were selected for four different kilovoltage/film speed combinations. Phantom bitewing radiographs, exposed using these exposure times, were processed using a variety of times and developer temperatures to simulate variations in radiographic quality due to inadequate processing conditions. Test films, produced using the four monitoring devices, were exposed and processed under identical conditions. The phantom bitewings were judged to have 'acceptable' quality when the optical density of that part of the film not showing calcified structures was within +/- 0.5 of that of the film processed under optimal conditions. The efficacy of the monitoring devices in indicating the adequacy of processing was assessed by a comparison of their readings with those made from the phantom bitewings. None of the monitoring devices was ideal for all the kilovoltage/film speed combinations tested, but the homemade device proved to be the most generally effective. We conclude that guidelines to dentists on radiographic quality assurance should include reference to and details of this simple device.

Densitometry↗

Real-time process/quality control for HPC processing.

BACKGROUND: JACIE Standards (FACT Standards in the USA) have been implemented in Europe since 1999. An on-site accreditation inspection took place at our center in January 2004. The purpose of this work was to develop a real-time process/quality control system meeting the JACIE Standards for HPC release. METHODS: Data from 194 HPC processing procedures for autologous transplantation performed over a 5-year period were analyzed. The results of different processing methods applied at our facility were compared: (1) cryopreservation without washing cells (n=50), (2) washing cells (n=87), (3) cell-density separation (n=12) and (4) positive CD34 selection (n=45). RESULTS: Four critical control points were set for the validation of HPC processing: (a) number of lost CD34(+) cells during processing, (b) contamination, (c) viability of the cells after thawing and (d) ability to reconstitute hematopoiesis after transplantation. On the basis of statistical analysis, ranges of acceptable values were defined for each critical control point and for each processing method. Those acceptable values were used for cell release and real-time quality control. DISCUSSION: This study describes a model for the validation of HPC processing and for a real-time process/quality control system for HPC release. Optimization of processing techniques, standardization of methods and comparison between facilities will open the way towards external quality controls and quality improvement.

Antigens, CD34↗

Application of the Deming management method to equipment-inspection processes.

The Biomedical Engineering staff at the Washington Hospital Center has designed an inspection process that optimizes timely completion of scheduled equipment inspections. The method used to revise the process was primarily Deming, but certainly the method incorporates the re-engineering concept of questioning the basic assumptions around which the original process was designed. This effort involved a review of the existing process in its entirety by task groups made up of representatives from all involved departments. Complete success in all areas has remained elusive. However, the lower variability of inspection completion ratios follows Deming's description of a successfully revised process. Further CQI efforts targeted at specific areas with low completion ratios will decrease this variability even further.

Biomedical Engineering↗

The rational selection of purification processes for proteins: an expert system for downstream processing design.

This paper describes the present state of the art in the use of ES for the rational selection of optimal purification processes for proteins (process synthesis). The main issues involved in selection of operations and process synthesis are reviewed. The high-resolution purification stages (one, two, three, or even more chromatographic steps where several alternatives in different orders of combinations can be used) have a combinatorial nature that can be represented by a "tree" structure. It can be analyzed by a depth-first or a breath-first approach. The two previous prototypes that have been developed are reviewed. The first prototype was exclusively based on "expert" rules, and its main weakness was in the selection of high-resolution purification operations for which a database of physicochemical properties of the main protein contaminants is needed. This was implemented in the second prototype in which a program for the calculation of separation coefficients on selection of high-resolution purification operations based on a preliminary database was interfaced. The present prototype being created uses a newly developed shell, which has an open architecture and uses object-oriented programming. This prototype uses a more "realistic" and accurate database (e.g., titration curves for contaminant proteins) and a tested method for selection of purification operations. The ES for selection of optimal protein separation sequences will give the user a number of alternatives chosen on the basis of the extensive data backup on proteins and unit operations.

Biotechnology↗

Modelling and optimization of a recombinant BHK-21 cultivation process using hybrid grey-box systems.

In this work a model-based optimization study of fed-batch BHK-21 cultures expressing the human fusion glycoprotein IgG1-IL2 was performed. It was concluded that due to the complexity of the BHK metabolism it is rather difficult to develop a kinetic model with sufficient accuracy for optimization studies. Many kinetic expressions and a large number of parameters are involved resulting in a complex identification problem. For this reason, an alternative more cost-effective methodology based on hybrid grey-box models was adopted. Several model structures combining the a priori reliable first principles knowledge with black-box models were investigated using data from batch and fed-batch experiments. It has been reported in previous studies that the BHK metabolism exhibits modulation particularities when compared to other mammalian cell lines. It was concluded that these mechanisms were effectively captured by the hybrid model, this being of crucial importance for the successful optimization of the process operation. A method was proposed to monitor the risk of hybrid model unreliability and to constraint the optimization results to acceptable risk levels. From the optimization study it was concluded that the process productivity may be considerably increased if the glutamine and glucose concentrations are maintained at low levels during the growth phase and then glutamine feeding is increased.

Animals↗

Support for information management in critical care: a new approach to identify needs.

Managing information is necessary to support clinical decision making and action in critical care. By understanding the nature of information management and its relationship to sound clinical practice, we should come to use technology more wisely. We demonstrated that a new approach inspired by ethnographic research methods could identify useful and unexpected findings about clinical information management. In this approach, a clinician experienced in a specific domain (critical care), with advice from a medical anthropologist, made short-term observations of information management in that domain. We identified 8 areas in a critical care Unit in which information management was seriously in need of better support. We also found interesting differences in how these needs were viewed by nurses and physicians. Our interest in this approach was at two levels: 1. Identify and describe representative instances of sub-optimal information management in a critical care Unit. 2. Investigate the effectiveness of such short-term observations by clinicians. Our long-range goal is to explore the use of this approach and the information it reveals to optimize the process of developing and selecting new information support tools, preparing for their introduction, and optimizing clinical outcomes.

Critical Care↗

Optimal operating mode for enantioseparation of SB-553261 racemate based on simulated moving bed technology.

The performance of the simulated moving bed (SMB) technology and its modification, the Varicol process, was optimized using an experimentally verified model for the enantioseparation of SB-553261 racemate. Single and multiobjective optimizations have been carried out for both existing as well as design stage and their efficiencies were compared. The optimization problem involves a relatively large number of decision variables, both continuous variables such as flow rates, switching time and length of the columns, as well as discrete variables like number and distribution of columns. A state-of-the-art new optimization technique based on a genetic algorithm (nondominated sorting genetic algorithm with jumping genes) was utilized which allows handling of these complex optimization problems. The optimization results showed that significant improvement could be made to the chiral drug separation process using both the SMB and the Varicol process. It was found that the performance of a Varicol process is superior to that of a SMB process in terms of treating more feed using less desorbent or increasing productivity while at the same time achieving better product quality. Optimum results were explained using equilibrium theory by locating them in the pure separation region.

Algorithms↗

Historical perspective of the Maillard reaction in food science.

Maillard's paper of 1912 describing the reaction between amino acids and sugars is both innovative and visionary. It provides original and still-valuable data on the chemistry of a new reaction and foresees its involvement in many scientific and biological domains, even in human pathology. This paper was ignored by the scientific community until 1941. In 1948 the Maillard reaction was definitely recognized as being responsible for the browning and loss of nutritive value of heated milk powders. There was then a continuous increase in papers on the chemistry of this complex reaction to identify its various pathways: in food science, to evaluate the influence of reaction parameters (pH, T degrees , time, sugar reactivity, concentration of the reagents, water activity, glass transition temperature) on the evolution of the reaction and on changes in food quality; in nutrition, to quantify the loss of bioavailability of essential amino acids; on the metabolism of the reaction products and on the physiological effects of the ingested Maillard reaction products. The significant scientific advances and the key persons and pioneers who contributed much to the understanding of the Maillard reaction are presented. The food industry is directly concerned with the occurrence of this reaction in processed foods and contributed significantly by its own research to understanding the phenomena and to optimizing the processes and conditions of food preparation in order to preserve the nutritional, safety, and organoleptic qualities of foods.

Food Industry↗

Prestimulus oscillations enhance psychophysical performance in humans.

The presence of various ongoing oscillations in the brain is correlated with behavioral states such as restful wakefulness or drowsiness. However, even when subjects aim to maintain a high level of vigilance, ongoing oscillations exhibit large amplitude variability on time scales of hundreds of milliseconds to seconds, suggesting that the functional state of local cortical networks is continuously changing. How this volatility of ongoing oscillations influences the perception of sensory stimuli has remained essentially unknown. We investigated the relationship between prestimulus neuronal oscillations and the subjects' ability to consciously perceive and react to somatosensory stimuli near the threshold of detection. We show that, for prestimulus oscillations at approximately 10, 20, and 40 Hz detected over the sensorimotor cortex, intermediate amplitudes were associated with the highest probability of conscious detection and the shortest reaction times. In contrast, for 10 and 20 Hz prestimulus oscillations detected over the parietal region, the largest amplitudes were associated with the best performance. Our data indicate that the prestimulus oscillatory activity detected over sensorimotor and parietal cortices has a profound effect on the processing of weak stimuli. Furthermore, the results suggest that ongoing oscillations in sensory cortices may optimize the processing of sensory stimuli with the same mechanism as noise sources in intrinsic stochastic resonance.

Adult↗

Optimization under variability and uncertainty: a case study for NOx emissions control for a gasification system.

Methods for optimization of process technologies considering the distinction between variability and uncertainty are developed and applied to case studies of NOx control for Integrated Gasification Combined Cycle systems. Existing methods of stochastic optimization (SO) and stochastic programming (SP) are demonstrated. A comparison of SO and SP results provides the value of collecting additional information to reduce uncertainty. For example, an expected annual benefit of 240,000 dollars is estimated if uncertainty can be reduced before a final design is chosen. SO and SP are typically applied to uncertainty. However, when applied to variability, the benefit of dynamic process control is obtained. For example, an annual savings of 1 million dollars could be achieved if the system is adjusted to changes in process conditions. When variability and uncertainty are treated distinctively, a coupled stochastic optimization and programming method and a two-dimensional stochastic programming method are demonstrated via a case study. For the case study, the mean annual benefit of dynamic process control is estimated to be 700,000 dollars, with a 95% confidence range of 500,000 dollars to 940,000 dollars. These methods are expected to be of greatest utility for problems involving a large commitment of resources, for which small differences in designs can produce large cost savings.

Air Pollution↗

Kinetic study of silica gels by a new rheological ultrasonic investigation.

The last decades have seen the development of sol-gel (SG) process currently used to develop new materials in a wide range of scientific applications. The SG process leads to an oxide macromolecular network through a sol (liquid phase) to gel transition. To optimize this process, the control of the kinetic of the chemical reaction is required. This kinetic can be deduced from the temporal evolution of the viscoelastic parameters. Upto date no complete investigation during the SG formation can be achieved by a unique non-destructive technique. In this paper, we present an ultrasonic technique to measure the viscoelastic parameters (storage G' and loss G'' shear moduli) of the gel material during its formation. By using a suitable model which takes into account the mass loading on the surface, the viscoelastic parameters of these materials are accurately deduced. In order to study the efficiency of this technique, silica gels transition is monitored at various formation temperatures and for different initial hydrolysis molar ratio (h). In addition, the monitoring is performed at different oscillatory shear measurements in the 6-54 MHz frequency range to determine a new characteristic time t(vs) corresponding to the moment when the material is no more a newtonian liquid. This characteristic time is then compared to the gelation time t(g) determined by rheological or acoustic audible range methods. Thus the new characteristic time is also a good criterion to characterize earlier the SG matrix transition. Our AT-cut quartz technique using our model can also be used as a high frequency rheometer for the sol-gel materials.

Algorithms↗

Optimization of a Bifidobacterium longum production process.

Bifidobacteria are used as probiotics mainly in the dairy industry as cell suspensions or as freeze-dried additives. So far there have been no reports on a thorough investigation on factors influencing the production process or a statistical approach to the optimization thereof. A 2(8-4) fractional factorial design was used in determining the critical parameters influencing bioreactor cultivations of Bifidobacterium longum ATCC 15707. Glucose, yeast extract and l-cysteine concentrations were found critical for the cultivation of this strain. Glucose and yeast extract concentrations were further studied together with temperature in a three factor central composite design. The optimized cultivation conditions were temperature 40 degrees C, yeast extract concentration 35 gl(-1) and glucose concentration 20 gl(-1). Freeze-drying of frozen cell suspensions of B. longum was studied first in controlled temperatures and thereafter with temperature programming experiments. The results were statistically evaluated. A temperature program with a 2 h temperature gradient from -10 to 0 degrees C, a 10 h temperature gradient from 0 to +10 degrees C and a 12 h temperature hold at +10 degrees C was found best for the freeze-drying process. Temperature programming reduced drying times by over 50% and improved the product activity by over 160%.

Bifidobacterium↗

Event-driven time-optimal control for a class of discontinuous bioreactors.

Discontinuous bioreactors may be further optimized for processing inhibitory substrates using a convenient fed-batch mode. To do so the filling rate must be controlled in such a way as to push the reaction rate to its maximum value, by increasing the substrate concentration just up to the point where inhibition begins. However, an exact optimal controller requires measuring several variables (e.g., substrate concentrations in the feed and in the tank) and also good model knowledge (e.g., yield and kinetic parameters), requirements rarely satisfied in real applications. An environmentally important case, that exemplifies all these handicaps, is toxicant wastewater treatment. There the lack of online practical pollutant sensors may allow unforeseen high shock loads to be fed to the bioreactor, causing biomass inhibition that slows down the treatment process and, in extreme cases, even renders the biological process useless. In this work an event-driven time-optimal control (ED-TOC) is proposed to circumvent these limitations. We show how to detect a "there is inhibition" event by using some computable function of the available measurements. This event drives the ED-TOC to stop the filling. Later, by detecting the symmetric event, "there is no inhibition," the ED-TOC may restart the filling. A fill-react cycling then maintains the process safely hovering near its maximum reaction rate, allowing a robust and practically time-optimal operation of the bioreactor. An experimental study case of a wastewater treatment process application is presented. There the dissolved oxygen concentration was used to detect the events needed to drive the controller.

Biomass↗