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At least 415 records · Page 23Linked to original sources

Optimal temporal differentiation.

In order to illuminate a light signaling a correct response, adult humans had to space their button presses according to a range of time requirements. In some conditions, the spacing needed only to exceed a minimum duration; in others, it had to fall between lower and upper bounds. Mean interresponse times always exceeded the lower limit, and decreased the more stringent were the upper bounds. Variability of interresponse times increased with larger lower bounds, but was unaffected by the size of the upper bound. Feedback about the direction of errors in conditions involving both upper and lower bounds did not affect the means, but it did reduce variability. Predictions were derived from optimality theory, based on the assumption that the critical factor was minimization of the time between correct responses. Without upper bounds, the theory overestimated the mean interresponse times by about 10%; with upper bounds, the theoretical predictions corresponded closely to the actual data. The results did not appear to reflect a scalar timing process. Optimality theory, in contrast to Weber's law, correctly predicted the variety of curves relating sensitivity to duration requirements.

Journal Article↗

Optimization of a dual echo in the steady state (DESS) free-precession sequence for imaging cartilage.

Three-dimensional (3D) MR imaging of the knee is useful to detect cartilage abnormalities, although the tissue contrast in 3D gradient-recalled echo (GRE) sequences such as gradient-recalled acquisition in the steady state (GRASS) or fast low-angle shot (FLASH) is poor. T2 contrast can be added to a GRASS sequence by combining the signals from the first and second gradient echoes, which form immediately after and immediately before each radio frequency (RF) pulse in a 3D GRE sequence. We have optimized a 3D dual echo in the steady state (DESS) sequence, which produces one averaged image from the two echoes, for use in the detection of articular cartilage abnormalities. In the optimization process, we examined the imaging parameters of flip angle (alpha), repetition time (TR), echo time (TE), and bandwidth to maximize the contrast between cartilage and joint fluid. A theoretical simulation of the sequence was confirmed with experiments conducted on phantoms with known T1 and T2. On the basis of theoretical predictions and experiments using healthy volunteers, we determined that an optimized sequence with a bandwidth of 98 Hz per pixel, TR of 30 msec, a TE of 7.1 msec, and an alpha of 60 degrees produced the highest contrast between cartilage and fluid within a defined acquisition time of 6 minutes. Additional contrast was obtained by filtering the second-echo image to eliminate noise before adding it to the first-echo image.

Cartilage, Articular↗

Control of long-term perfusion Chinese hamster ovary cell culture by glucose auxostat.

The strategies for control of the feed rate in high-density perfusion cultures of animal cells are limited to several simple schemes. While in an industrial environment simplicity is seen as a major advantage, the need for more elaborate closed-loop control methods that can improve process stability in long-term continuous cultures is also well understood. What has prevented the application of the advanced control strategies known from theory is the lack of reliable real-time information that can be used to close the feedback loop. Among the variables that are appropriate for direct feedback control of the perfusion rate, high priority should be given to the glucose concentration. Unlike some other environmental variables, such as dissolved oxygen and pH, it provides unambiguous information which facilitates the selection of the right feed rate. The present paper describes the application of a closed loop control scheme, known as a "glucose-stat", to the long-term cultivation of Chinese hamster ovary cells in a high-density (35-40 million cells/mL) perfusion process. The monitoring and control system worked successfully for more than 2.5 months without any signs of performance degradation. In targeting industrial application, issues such as reliability, sterility, and accuracy, are given high priority. The implementation of the glucose monitoring system, which is the main part of the control complex, is addressed in details. The performance of the perfusion culture was evaluated at four different glucose set points, providing essential information about process optimization. It became evident that the perfusion culture was operated in the so-called "high-gain" zone (where the system is highly sensitive to the dilution rate), which justifies the application of a feedback control. The on-line glucose concentration was also used by an embedded expert system which drove the process through the batch and the perfusion phase, achieving total computer control of the feed rate. In summary, the proposed glucose monitoring and control technique proved to be a reliable biotechnology tool which can be applied with confidence at an industrial scale to either microbial or mammalian cell cultures.

Animals↗

Advances in multivariate analysis in pharmaceutical process development.

In the last five years, reports of the application of multivariate methods in pharmaceutical process research and development have burgeoned. Examples range from the widespread adoption of statistical experimental design for screening and process optimization to the implementation of workflows that integrate multivariate characterization, experimental design and the development of quantitative structure-property relationships. Having learned from the application of these techniques in drug discovery and armed with modern high-throughput experimentation platforms, practitioners are discovering the power of experimental design and multivariate methods for shortening process development timelines.

Drug Evaluation, Preclinical↗

A multi-scale study of industrial fermentation processes and their optimization.

In this article problems in multi-scale industrial fermentation processes are discussed. The problems are generated virtually, by using computer simulation on three different scales--the molecular scale (genetics), the cellular scale (metabolic regulation), and the reactor engineering scale. Inter-scale observation and operation are deemed to be crucial in the optimization of bioprocesses. Bioreaction engineering based on metabolic flux analysis and control is further elucidated. Optimization methodology for study of multi-scale problems in a fermentation process, based on correlation of data, and the scale-up technique for regulation of several bioprocess parameters are generalized by investigation of two typical fermentation processes. A novel bioreactor system was designed to monitor mass flux (for example substrates and (by-)products) in a fermentation process. It was successfully applied to the optimization and scale-up of an industrial fermentation process for penicillin, erythromycin, chlortetracyclin, inosine, and guanosine, and for production of recombinant human serum albumin and a malaria vaccine by use of the Pichia expression system. Substantial improvement of industrial fermentation productivity was achieved.

Bioreactors↗

Application of LIBS to the in-line process control of liquid high-alloy steel under pressure.

A process optimization and control system called VAI-CON Chem has been developed that uses laser-induced breakdown spectroscopy (LIBS) to quasi-continuously chemically analyze liquid high-alloy steel under pressure. The beam from a Nd:YAG laser, located on safe ground and operating at its fundamental wavelength, is guided by a mirror system to a process tuyere below bath level. Passing through the approximately 1.5 m long tuyere, the beam is then focused onto the steel bath. Light emitted from the induced plasma passes back through the tuyere, which is coupled to a fiber optic cable that carries the information over a distance of approximately 10 m back to an Echelle spectrometer located beside the laser. Calibrations were performed using the complete system, located in a laboratory, during system testing. An induction furnace was used to simulate the AOD converter, wherein the samples were molten and superheated to a temperature of approximately 1600 degrees C and kept at a pressure of approximately 1.7 bar under an argon atmosphere. Twelve different high alloyed reference samples taken from normal AOD production with Fe concentrations of >48 wt.% and non-Fe element concentrations of up to 25 wt.% were available for calibration. The mean residual deviations (defined as the square root of the variance of the concentration ratios determined by LIBS and the reference element concentration ratios) obtained were close to those reported for other comparable high-alloy samples that were investigated at room temperature under normal atmospheric pressure.

Journal Article↗

On the clinical relevance of mismatch negativity: results from subjects with normal hearing and cochlear implant users.

Mismatch negativity (MMN) provides an objective measure for evaluating subjects with problems related to speech processing. For a valid neurophysiological profile of speech-processing mechanisms, an efficient procedure to elicit MMNs is needed. In Experiment 1 of this study, MMN recordings were conducted in adults with normal hearing on the effects of decreasing the duration of the interstimulus interval (ISI). Shortening ISI duration does not seem to have a high impact on the individual MMN quality, whereas it does influence group MMN quality. In Experiment 2, MMNs were elicited in a group of cochlear implant users by using a speech sound contrast/ba/-/da/. A group of good performers produced a significant MMN, whereas a group of moderate performers did not. There seems to be a relation between speech perception ability and MMN quality. To fundamentally understand the effects of electrical stimulation of the inner ear and to clinically adjust rehabilitation, diverse data are needed on different aspects of auditory processing. Optimizing the procedure to elicit and MMN is therefore of great clinical value.

Adult↗

Application of ferric sludge to immobilize leachable mercury in soils and concrete.

A Hg-contaminated site in B.C. Province, Canada was caused by the previous operation of Hg-cell in chlor-alkali process for over 25 years. The soils and groundwater at the site are highly contaminated with mercury. An analysis of groundwater at the site has shown that most of the mercury is bonded with humic and fulvic acids (HFA) in colloidal form. The Hg-HFA colloids can be completely removed from the groundwater with ferric chloride treatment under optimized process conditions to form ferric sludge (FS), which is rendered non-leachable by standard TCLP (Toxicity Characteristic Leaching Procedure) test. The effluent discharged from a clarifier has achieved mercury levels of < 0.5 microkg l(-1). The studies of mercury adsorption characteristics of FS show it has low mercury leachability by TCLP, and great mercury adsorption capability. This feature is the basis for the application of FS to immobilization of leachable Hg-contaminants in solid wastes. Full-scale stabilization tests of Hg-contaminated soil have been carried out, and the time-based stability of the treated soil has been monitored by TCLP over a period of 60 days. All the results have shown a small variation in TCLP mercury levels within a range of 10-40 microg l(-1). Based on these results and with the approval of the B.C. Ministry of the Environment, 1850 tons of Hg-contaminated soils and 260 tons of Hg-contaminated concrete fines have been treated, stabilized with FS, and disposed in a non-hazardous waste disposal site.

Ferric Compounds↗

Optima: a windows-based program for computer-aided optimization of controlled-release dosage forms.

The purpose of this work was to develop a computer program that assists optimization of controlled-release devices, both visually and mathematically, using response surface methodology (RSM). A Windows-based computer program, Optima, which interactively implemented a number of subroutines for the optimization procedure, was developed. Optima is an integrated, user-friendly, and graphically oriented program for pharmaceutical dosage form optimization. Central composite design is implemented in the program. First- and second-order models containing up to five variables can be fitted to the data. The user can also choose between linear and exponential individual desirability functions, and use them to construct an overall desirability function that combines all the response variables in a single response. The program can predict the optimum levels of experimental variables, with respect to individual responses and/or the overall desirability. Optima has been successfully used in the development of sustained-release AZT-loaded microspheres. During the optimization process, three experimental variables were investigated and four responses were measured. The experimental design was a central composite design that was generated by the program. The response values were used by the program to calculate the individual desirability functions, which were then combined into an overall desirability function. The individual responses as well as the overall desirability function were optimized by fitting to a second-order polynomial equation. The response surfaces were generated and optimum levels of the experimental variables were predicted. The observed responses of the optimized formulation were very close to those predicted by Optima. The program proved to be a very useful, integrated tool for optimization of the controlled-release microspheres.

Computer Graphics↗

[Study on the extraction of indirubin from Isatis indigotica Fort].

OBJECTIVE: To study the optimal process of the extraction of indirubin from Isatis indigotica Fort. METHODS: The process was studied by supersonic extraction, refluxing and orthogonal design with the content of indirubin as the detective marker. Then the extraction of indirubin with supersonic extraction and other methods were compared basing on the yield of extracts. RESULTS: Among them, the supersonic extraction was the simplest and the most rapid and the most complete in extraction. And the optimal conditions were A1 B1 C2 D3: supersonic extraction with 60% ethanol, 1 hour, 10-fold solvent and 3 times. CONCLUSION: The supersonic extraction can extract more indirubin from Isatis indigotica Fort in shorter time with less energy. It also shows a promising prospect for leaching the effective constituents from Chinese herbal medicine by supersonic extraction.

Analysis of Variance↗

Anaerobic digestion of alfalfa silage with recirculation of process liquid.

Process liquid recirculation initially stimulated one-phase anaerobic digestion of alfalfa silage in two semi-continuously fed and stirred tank reactors. Thus, with increased pH, alkalinity and stability it was possible to increase the organic loading rate to 3 g VS L(-1) d(-1), as compared to 2.25 g VS L(-1) d(-1) in a control reactor without recirculation. However, the recirculation of liquid eventually caused an accumulation of organic and inorganic substances, leading to an inhibition of hydrolysis and methanogenesis. This inhibition of microbial activity was prevented in one of the processes by replacing 50% of the recirculated process liquid with water during the second half of the operation period. A multiple linear regression model of principal components using seven input variables explained the variance in output variables nearly as well as the original model using all 23 measured input variables. The results show that it is necessary to adjust the degree of liquid recirculation to reach an optimal process.

Anaerobiosis↗

Numerical simulation for heat transfer in prostate cancer cryosurgery.

A comprehensive computational framework to simulate heat transfer during the freezing process in prostate cancer cryosurgery is presented. Tissues are treated as nonideal materials wherein phase transition occurs over a temperature range, thermophysical properties are temperature dependent and heating due to blood flow and metabolism are included. Boundary conditions were determined at the surfaces of the commercially available cryoprobes and urethral warmer by experimental study of temperature combined with a mathematical optimization process. For simulations, a suitable computational geometry was designed based on MRI imaging data of a real prostate. An enthalpy formulation-based numerical solution was performed for a prescribed surgical protocol to mimic a clinical freezing process. This computational framework allows for the individual planning of cryosurgical procedures and objective assessment of the effectiveness of prostate cryosurgery.

Body Temperature↗

Treatment planning optimization by conjugate gradients and simulated annealing methods in stereotactic radiosurgery.

PURPOSE: This paper presents a new optimization method of treatment planning in linac stereotactic radiosurgery. METHODS AND MATERIALS: On a workstation integrating x-rays, computed tomography (CT), magnetic resonance imaging (MRI), and digital subtracted angiography (DSA) images, we first determine the outlines of the target volume and surrounding healthy tissues to spare. To achieve complete optimization of the treatment plans, this method decomposes the optimization process in two steps. The position of the isocenters and the diameter of the collimators are first deduced by a conjugate gradients method, from the position and size of ellipsoids or spheres modeling the target volume. The other irradiation parameters, such as the isocenter dose, the aperture, and the weight of each irradiation plane and of their irradiation sectors are finally deduced by a simulated annealing optimization algorithm. RESULTS: The system can perform multitarget/multisector treatment plans that are automatically obtained in a satisfactory time (as a rule, 20 min for a two-target irradiation), much faster than the time needed for a manual treatment planning. We present the results in two cases: the simulation of a single-target treatment and a two-target real treatment with constraints. In these two cases, we can control the dose received by target and sensitive volumes. CONCLUSION: This method achieves an excellent conformation of the estimated isodose curves with the outlines of the target volume, which allows us to avoid the surrounding healthy tissues, thanks to the different weighting factors given on each volume concerned according to the importance we grant to each of them.

Angiography, Digital Subtraction↗

Elimination of adverse leakage flow in a miniature pediatric centrifugal blood pump by computational fluid dynamics-based design optimization.

We investigated a miniature magnetically levitated centrifugal blood pump intended to deliver 0.3-1.5 l/min of support to neonates and infants. The back clearance gap between the housing and large volume of the rotor, where the suspension and motor bearings are located, forms a continuous leakage flow path. Within the gap, flow demonstrates a very complex three-dimensional structure: the fluid adjacent to the rotating disk tends to accelerate by centrifugal force to flow radially outwards toward the outlet of the impeller against an unfavorable pressure gradient, which in turn forces blood to return along the stationary housing surfaces. Consequently, one or multiple vortices may be generated in the gap to block blood flow and cause the formation of a retrograde and antegrade leakage flow phenomenon at the gap outlet using an optimization process including extensive computational fluid dynamics (CFD) analysis of impeller refinements, we found that secondary blades located along the back or extended to the side surfaces of the rotor have the capacity to reduce and eliminate the retrograde flow in the back clearance gap. Flow visualization confirmed the CFD-predicted flow patterns. This work demonstrates the utility of CFD-based design optimization to optimize the fluid path of a miniature centrifugal pump.

Centrifugation↗

Minimal work principle: proof and counter-examples.

The minimal work principle states that work done on a thermally isolated equilibrium system is minimal for adiabatically slow (reversible) realization of a given process. This principle, one of the formulations of the second law, is studied here for finite (possibly large) quantum systems interacting with macroscopic sources of work. It is shown to be valid as long as the adiabatic energy levels do not cross. If level crossing does occur, counter-examples are discussed, showing that the minimal work principle can be violated and that optimal processes are neither adiabatically slow nor reversible. The results are corroborated by an exactly solvable model.

Journal Article↗

A genetic segmentation of ECG signals.

This paper is concerned with a development of a segmentation technique for electrocardiogram (ECG) signals. Such segmentation is aimed at a lossy signal compression in which each segment can be captured by a simple geometric construct such as, e.g., a linear or quadratic function. The crux of the proposed construct lies in the determination of the optimal segments of data over which they exhibit the highest possible monotonicity (or lowest variability) of the ECG signal. In this sense, the proposed approach generalizes a fundamental and commonly encountered problem of function (data) linearization. The segments are genetically developed using a standard technique of genetic algorithms (GAs). The two fundamental GA constructs, namely a topology of a chromosome and a fitness function governing the optimization process are discussed in detail. The chromosome being coded as a series of floating point numbers contains the endpoints of the segments (segmentation points). The fitness function to be maximized quantifies a level of monotonicity of the ECG data encountered within the segments and takes into consideration differences between the extreme values (minimum and maximum) of its derivatives. As a result of the genetic optimization, we build segments of ECG signals encompassing monotonic (increasing or decreasing) regions of the signal exhibiting a minimal level of variability. A series of experiments dealing with several classes of ECG signals (namely, normal, left bundle branch block beat, and right bundle branch block beat) visualize the effectiveness of the approach and shows the specificity of the linear segments of data. Furthermore, we elaborate on the relationship between the values of the fitness function and the approximation capabilities (quantified by a sum of squared errors between the local model and the data) of the segments of the signal and show that these two descriptors are highly related.

Algorithms↗

Spatial alignment across gaps: contributions of orientation and spatial scale.

To assess the contributions of orientation and spatial scale to the processing of relative-position information for broadband spatial targets, we measure misalignment thresholds for dots separated by as much as 6 deg, in the presence of one-dimensional spatial noise. For all the dot separations, thresholds for misalignment are raised most when the mask is oriented at approximately 20 deg to either side of true alignment. This bimodal orientation tuning function appears to be fundamental to the alignment judgment, including abutting vernier acuity for equally visible lines [Vision Res. 33, 1619 (1993)]. With increasing dot separation the spatial frequency at which peak masking occurs becomes progressively lower, a finding that suggests that the spatial mechanisms important for processing this information become larger. However, the rate of increase in size of these putative mechanisms is insufficient to account for the increase in relative-position thresholds for increasingly separated stimuli (i.e., Weber's law for alignment). In addition, oriented masks placed between two target lines lead to threshold elevation, revealing that the collection of positional information between target features may be important for optimal processing of misalignment thresholds. The findings of this study suggest that, although shifts in spatial scale of the underlying low-level oriented mechanisms may contribute to increased misalignment thresholds with increasing separation, additional factors, such as positional uncertainty associated with eccentricity per se, are limiting.

Contrast Sensitivity↗

The calculation of the vibrational frequencies of crystalline compounds and its implementation in the CRYSTAL code.

The problem of numerical accuracy in the calculation of vibrational frequencies of crystalline compounds from the hessian matrix is discussed with reference to alpha-quartz (SiO(2)) as a case study and to the specific implementation in the CRYSTAL code. The Hessian matrix is obtained by numerical differentiation of the analytical gradient of the energy with respect to the atomic positions. The process of calculating vibrational frequencies involves two steps: the determination of the equilibrium geometry, and the calculation of the frequencies themselves. The parameters controlling the truncation of the Coulomb and exchange series in Hartree-Fock, the quality of the grid used for the numerical integration of the Exchange-correlation potential in Density Functional Theory, the SCF convergence criteria, the parameters controlling the convergence of the optimization process as well as those controlling the accuracy of the numerical calculation of the Hessian matrix can influence the obtained vibrational frequencies to some extent. The effect of all these parameters is discussed and documented. It is concluded that with relatively economical computational conditions the uncertainty related to these parameters is smaller than 2-4 cm(-1). In the case of the Local Density Approximation scheme, comparison is possible with recent calculations performed with a Density Functional Perturbation Theory method and a plane-wave basis set.

Journal Article↗