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Optimal solution, quantitative performance estimation, and robust tuning of the simplifying controller.

Recently, a simplifying controller has been proposed based on the principal of simplification of the control system transfer functions, which offers improved control for processes with a large time delay. It is the purpose of this complementary paper to give a comprehensive analysis on the scheme. First, the relationship among the simplifying controller, the Smith predictor, and the internal model control are discussed. Second, an analytical design procedure is developed based on internal model control (IMC) and optimal solution is derived. Third, the problem of estimating the time domain performance of the closed loop system, quantitatively, is discussed. Fourth, a simple robust tuning procedure is presented. Numerical examples are provided to illustrate the proposed method.

Computer Simulation↗

Nominal and robust stability regions of optimization-based PID controllers.

In recent decades, several optimization-based methods have been developed for the proportional-integral-derivative (PID) controller design, and the common feature of these methods is that the controller has only one adjustable parameter. To keep the closed-loop systems stable is an essential requirement for the optimization-based PID controllers. In almost all these methods, however, no exact stability region for the single adjustable parameter was sketched. In this paper, using the proposed analytical procedure based on the dual-locus diagram technique, explicit stability regions of the optimization-based PID controllers are derived for stable, integrating, and unstable processes with time delay in the nominal and perturbed cases, respectively. It is revealed that the proposed analytical procedure is effective for the determination of the nominal and robust stability regions and it offers simplicity and ease of mathematical calculations over other available stability analysis methods. The results in this paper provide some insight into the tuning of the optimization-based PID controllers.

Algorithms↗

Robust on-line relay automatic tuning of PID control systems

In this paper, a robust on-line relay automatic tuning method for PID control systems is developed which expand on the application domain of Astrom's renowned relay autotuning method. In the proposed configuration, a relay is applied to an inner loop of a controller-stabilised process in the usual manner. Using the induced limit cycle oscillations from the closed-loop system, the controller settings may be re-tuned non-iteratively to achieve enhanced performance without disrupting closed-loop control. Two control tuning methodologies are developed -- a direct and an indirect method based on an explicit process model. Simulation examples and a real-time experiment are provided to illustrate the practical appeal and potential advantages of the proposed method over the basic one.

Journal Article↗

Development and robustness testing of a nonaqueous capillary electrophoresis method for the analysis of nonsteroidal anti-inflammatory drugs.

Nine non steroidal anti-inflammatory drugs were simultaneously separated by nonaqueous capillary electrophoresis with a methanol-acetonitrile (40:60, v/v) mixture containing 20 mM ammonium acetate. The effect of solvent composition, electrolyte nature and concentration on the electrophoretic behavior of the selected drugs was systematically studied. Investigated electrolytes were ammonium, lithium and sodium acetate. Modification of the solvent and/or the electrolyte composition was found to alter the migration order of the pharmaceutical drugs. Finally, to assess method robustness, three sensitive electrophoretic parameters as well as their interactions were evaluated using a full factorial design at two levels.

Acetates↗

Why robust background electrolytes containing multivalent ionic species can fail in capillary zone electrophoresis.

In this paper it is demonstrated that system peaks are induced by multivalent weak ionic species in background electrolytes. Their existence is derived from SystCharts and from Peak Shape Diagrams and the theory is confirmed experimentally. If analytes are present in a sample, with mobilities approximately equal to the mobility of a system peak, they interact, resulting in a strong increase of electromigration dispersion. This leads to strong peak broadening, peak deformation and a loss of resolution. Typical background electrolytes containing multivalent ionic species, e.g. phosphate and phthalate buffers, often reported to be robust electrolytes, are therefore not always universally applicable and can fail for the application of specific analytes. This paper reports a systematic study of the above phenomena and shows both theoretical and experimental results for background electrolytes containing phosphoric acid and phthalic acid.

Electrolytes↗

Impact of normal-phase gradient elution in chiral chromatography: a novel, robust, efficient and rapid chiral screening procedure.

Novel normal-phase gradient systems have been employed for fast high-throughput chiral analyses of Discovery compounds in our research laboratories in Eli Lilly and Company. In this report, we describe an automated screening approach based on gradient elution, in order to achieve accurate enantiomeric excess determinations, and chiral separations when needed, in the shortest possible timeframe. Baseline resolution of enantiomers has been obtained for over 85% of the samples so tested. For the remaining cases, complete enantioseparation by isocratic optimisation is generally achieved in a single shot. This technique has been proven to be robust and is now standard operating procedure at our analytical research laboratories.

Chemistry, Pharmaceutical↗

Robust and simple interface for microchip electrophoresis-mass spectrometry.

A robust and simple interface for microchip electrophoresis-mass spectrometry (MCE-MS) was developed using a spray nozzle connected to the exit of the separation channel of the microchip. The spray nozzle was attached to the microchip using a polyether ether ketone screw without adhesive, thus allowing easy replaced. Sample injection and electrophoretic separation was performed by control of the voltage only. The analysis of a few basic drugs was performed using the optimized MCE-MS system. The separation was improved by using a high-viscosity separation buffer and a spray nozzle with a small bore size. This system was also applied to the separation of peptides and protein-trypsin digests. Sample adsorption was minimized by adding acetonitrile to the separation buffer when using a quartz microchip.

Mass Spectrometry↗

Direct fractionation of proteins in particle-containing feedstocks by a filter paper pieces-based DEAE-cellulose column chromatography. Rapid, robust and low-cost capturing procedure for protein.

Filter paper pieces-based (FPB) DEAE-celluloses was prepared for direct fractionation of proteins in particle-containing feedstocks. FPB DEAE-cellulose has a protein binding capacity equivalent to that of commercially available DEAE-cellulose. Crude extracts from porcine intestine and kiwi fruit pulp, which were unmanageable by commercially available chromatographic media due to rapid clothing, could be directly fractionated with FPB DEAE-cellulose column. In addition, effluents from an FPB DEAE-cellulose column were extensively clarified. The present approach can be used as a rapid, robust and low-cost capturing step for protein from particle-containing feedstocks.

Animals↗

The dynamics of T-cell fratricide: application of a robust approach to mathematical modelling in immunology.

Fratricide between CD8(+) T lymphocytes is known to occur in HTLV-I and possibly HSV-1 and HIV-1 infection. However it is not known what effect, if any, T-cell fratricide has on the course of infection. Here we present simple mathematical techniques to investigate T-cell fratricide with particular reference to HTLV-I infection. Using a general model we predict the qualitative and quantitative effect of fratricide on HTLV-I equilibrium proviral load. We also investigate the effect of fratricide on the probability of viral clearance. We show that, surprisingly, fratricide can lead either to an increase or a decrease in equilibrium proviral load. We derive the conditions necessary for fratricide to cause a decrease in load and deduce that, for the five HTLV-I-positive patients considered here, fratricide has probably caused an increase in equilibrium load. We also estimate the percentage increase in load that is attributable to fratricide and determine the parameters that should be measured in order to improve this estimate. Finally, we show that fratricide reduces the probability of viral clearance. Mathematical modelling of HTLV-I infection, as is often the case in biology, is severely hampered by a lack of experimental data. Consequently it is difficult to know what functional form a model should take. The behaviour of complex nonlinear systems is highly model-dependent. Predictions based on theoretical models are therefore sensitive to the choice of model; this is a very severe problem that undermines and limits the success of the application of mathematics to immunology. In this paper we reduce the model dependency of the results in two ways-by considering (analytically) a general model with a minimal number of assumptions and, where this is not possible, by checking (numerically) that a wide range of models yield the same results. We therefore begin to develop two practical methods for dealing with the problem of robustness in mathematical models of the immune system.

CD8-Positive T-Lymphocytes↗

Sampling effects and the robustness of quantitative and qualitative food-web descriptors.

Food-web descriptors serve as a means for among-web comparisons that are necessary for the discovery of regularities in respect to food-web structure. Qualitative descriptors were however found to be highly sensitive to varying levels of sampling effort. To circumvent these shortcomings, quantitative counterparts were proposed which take the magnitude of trophic interaction between species into consideration. For 14 properties we examined the performance with increasing sampling effort of a qualitative, an unweighted quantitative (giving the same weight to each taxon), and a weighted quantitative version (weighing each taxon by the amount of incoming and outgoing flows). The evaluation of 10 extensively documented quantitative webs formed the basis for this analysis. The quantitative versions were found to be much more robust against variable sampling effort. This increase in accuracy is accomplished at the cost of a slight decrease in precision as compared to the qualitative properties. Conversely, the quantitative descriptors also proved less sensitive to differences in evenness in the distribution of link magnitude. By more adequately incorporating the information inherent to quantitative food-web compilations, quantitative descriptors are able to better represent the web, and are thus more suitable for the elucidation of general trends in food-web structure.

Animals↗

Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range.

PURPOSE: Prostate specific antigen (PSA) cutoffs lower than 4.0 ng./ml. are being evaluated more frequently but lower PSA cutoffs increase the number of prostatic biopsies. PSA exists in several forms free and complexed to proteins. Percent free PSA is lower in men with prostate cancer. Accordingly, free PSA and complexed PSA have been used to distinguish between cancer and benign disease in the diagnostic gray zone of 4 to 10 ng./ml. to eliminate unnecessary biopsies. There are limited data on the robustness of free PSA measurements in the 2.6 to 4.0 ng./ml. total PSA range. MATERIALS AND METHODS: We evaluated percent free PSA measurements to discriminate between cancer and benign conditions in 965 consecutive volunteers in a prostate cancer screening study who underwent prostatic biopsy for a PSA of 2.6 to 4.0 ng./ml. and had benign digital rectal examination. RESULTS: Overall 25% of men had cancer detected. A 25% free PSA cutoff detected 85% of cancers and avoided 19% of negative (cancer-free) biopsies, while a 30% free PSA cutoff detected 93% of cancers and avoided only 9% of negative biopsies. Of those men who underwent radical prostatectomy 132 (80%) had pathologically organ confined tumors. Only 5% of these tumors fulfilled the published pathological criteria for possibly clinically unimportant tumors. CONCLUSIONS: Percent free PSA provides risk assessment but does not eliminate many unnecessary prostatic biopsies while maintaining a high sensitivity in the narrow total PSA range of 2.6 to 4.0 ng./ml.

Adult↗

Effects of epistasis on phenotypic robustness in metabolic pathways.

It is an open question whether phenomena such as phenotypic robustness to mutation evolve as adaptations or are simply an inherent property of genetic systems. As a case study, we examine this question with regard to dominance in metabolic physiology. Traditionally the conclusion that has been derived from Metabolic Control Analysis has been that dominance is an inevitable property of multi-enzyme systems and hence does not require an evolutionary explanation. This view is based on a mathematical result commonly referred to as the flux summation theorem. However it is shown here that for mutations involving finite changes (of any magnitude) in enzyme concentration, the flux summation theorem can only hold in a very restricted set of conditions. Using both analytical and simulation results we show that for finite changes, the summation theorem is only valid in cases where the relationship between genotype and phenotype is linear and devoid of non-linearities in the form of epistasis. Such an absence of epistasis is unlikely in metabolic systems. As an example, we show that epistasis can arise in scenarios where we assume generic non-linearities such as those caused by enzyme saturation. In such cases dominance levels can be modified by mutations that affect saturation levels. The implication is that dominance is not a necessary property of metabolic systems and that it can be subject to evolutionary modification.

Computer Simulation↗

Factors affecting the robustness of metabolite fingerprinting using 1H NMR spectra.

1H NMR spectroscopy is one of the techniques whose potential is currently being explored in the emerging field of metabolomics. It is a non-targeted method, producing signals for all proton-containing chemical species. For crude plant materials the spectra are always complex, with many signals overlapping. Hence a most suitable approach for analysing them is 'metabolite fingerprinting', which is aimed at highlighting compositional similarities and exploring the overall natural variability in a population of samples. The most commonly used method for this is principal component analysis (PCA), as it allows the whole spectral trace to be analysed and the vast quantity of information to be simplified. In this paper we investigate whether there are factors which may affect the NMR spectra in a way that subsequently decreases the robustness of the metabolite fingerprinting by PCA. Imperfections in the signal registration (i.e. inconsistency of the peak position) are generally detrimental to analysing whole traces by multivariate methods. The sources of such problems are illustrated through specially designed repeatability studies using potato and tomato samples, and the analysis of a tea dataset containing many samples. Careful sample preparation can help to limit peak shifts; for instance here by attempting to control the pH of the extracts. In addition, some compounds are susceptible to interactions affecting their chemical shifts and mathematical alignment of peaks may be necessary. Lastly factors such as resolution can also affect analyses and must be carefully adjusted. Our choice of examples aims to raise awareness of potential problems. We do not question the validity of the NMR approach, but point out those areas where special care may need to be taken.

Databases, Factual↗

Combining phase and energy detection with mathematical morphology in dual time-frequency representation leads to improved SSP noise robustness.

In this paper a fusion algorithm for the detection of specular echoes blurred by coloured Gaussian noise is proposed. The phase and energy criteria, characteristic of these echoes, are handled separately. First, the detection capabilities of split spectrum (phase) and short time Fourier transform spectrogram (energy) are compared theoretically and experimentally. Second, the new algorithm based on mathematical morphology operators using both time-frequency representations is proposed. In the last part our method is shown to be more robust than absolute minimisation split spectrum processing.

Algorithms↗

The influence on partial order ranking from input parameter uncertainty. Definition of a robustness parameter.

The method of partial order ranking has been used within the environmental area for a variety of purposes as an attractive way of handling complex information. However, the environmental data are often associated with a significant degree of uncertainty. In this investigation the general nature of the influence from data uncertainty on the partial order ranking is analyzed. A Monte Carlo type analysis is performed in which a series of randomly formed data are used to test the influence of data uncertainty. The partial order ranking is interpreted, where the results are transferred to a one-dimensional ranking scale taking into account that not all elements are ranked with the same certainty. A simple general robustness parameter (E) in form of the expected number of comparisons for each ranking element is defined and correlated to the uncertainty analysis results. A simple equation relates E to the number of elements and the number of parameters, respectively. The magnitude of the ranking uncertainty is shown to increase rapidly when the E value decreases below 4-5 comparisons per element. When the E value exceeds 5 the ranking uncertainty becomes nearly constant and independent on the actual E value.

Environmental Monitoring↗

Progressive study and robustness test of QSAR model based on quantum chemical parameters for predicting BCF of selected polychlorinated organic compounds (PCOCs).

Systematic analyses on the effects of chemical structures of 31 polychlorinated organic compounds (PCOCs) on their bioconcentration behavior in rainbow trout (Oncorhynchus mykiss) were conducted using quantitative structure-activity relationship (QSAR) techniques. The cluster analyses of individual variables as well as the quality control chart of QSAR model implies the existence of outliers, while the simulation model excluding such samples showed an extreme robustness even if it was tested with different methods. Furthermore, the quantum chemical parameters entering into QSAR model were used to describe the bioconcentration pathways, and the results indicated that bioconcentration behaviors of selected compounds were complicated processes involving permeation stages as well as bio-chemical reaction stages.

Animals↗

Robust colorimetric assays for dynamin's basal and stimulated GTPase activities.

Dynamin, unlike many GTPase superfamily members, exhibits a relatively rapid basal rate of GTP hydrolysis that is not rate-limited by GTP binding or GDP dissociation. Also unique to dynamin GTPase family members is their ability to self-assemble into rings and helical stacks of rings either in solution or onto lipid templates. Self-assembly stimulates dynamin's GTPase activity by >100-fold. Given these robust rates of GTP hydrolysis compared to most GTPases, GTP hydrolysis by dynamin can be easily measured using a simple colorimetic assay to detect released phosphate. We describe this assay and report variations in assay conditions that have contributed to the wide range of reported values for dynamin's basal and assembly-stimulated rates of GTP hydrolysis.

Animals↗

The disruption of prepulse inhibition by social isolation in the Wistar rat: how robust is the effect?

Postweaning isolation rearing in rats is shown to have consequences for the expression of numerous behaviors. The present studies investigated isolation-induced disruptions of the prepulse inhibition (PPI) response in the Wistar rat strain, as a function of exposure of the animals to locomotor activity testing. Further, repeated testing of PPI was investigated to examine the robustness of the isolation-induced disruptions. The results indicate that experimentally naive isolation-reared animals exhibit disruptions in the PPI response that are retained in a second test 7 days later. The disruptions obtained are shown to be consistent across all pulse frequencies examined and independent of effects on startle. Exposure to activity testing, however, either before or after the measurement of PPI, abolished the isolation-induced disruption of PPI in a subsequent test. In contrast, locomotor activity testing consistently revealed a hyperactivity response in isolation-reared animals that was not influenced by the temporal occurrence of the testing. The findings are discussed relative to the interpretation of data emerging from studies where both activity testing and PPI are performed in the same animals, and in the relation to the use of PPI in isolation-reared animals as representing a nonpharmacological animal model of schizophrenia.

Acoustic Stimulation↗