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PubMed2005

Accuracy and robustness of three-way decomposition applied to NMR data.

Three-way decomposition is a very versatile analysis tool with applications in a variety of protein NMR fields. It has been used to extract structural data from 3D NOESYs, to determine relaxation rates in large proteins, to identify ligand binding in screening for lead compounds, and to complement non-uniformly recorded (sparse) spectra. All applications so far concerned experimental data sets; it thus remains to address questions of accuracy and robustness of the method using simulated data where the correct answer is known. Systematic tests are presented for relaxation and NOESY data sets. Mixtures of real and synthetic data are used to allow control of various parameters and comparisons with correct reference data, while working with input that is as realistic as possible. The influence of the following parameters is evaluated: signal-to-noise, overlap of signals and the use of a regularization procedure within the algorithm. The main criteria used for the evaluation are accuracy and precision. It is shown that deterioration of accuracy is indicated by internal checks such as decrease of precision. Both with relaxation data and when interpreting NOESY spectra, three-way decomposition exhibits a robust behavior in situations with severe signal overlap and/or poor signal-to-noise, e.g., by avoiding false positives in the NOE shapes of NOESY decompositions. As a complement to this study, three-way decomposition is compared to other methods that achieve the same type of results.

Algorithms↗
PubMed2005

Trimmed estimators for robust averaging of event-related potentials.

Averaging (in statistical terms, estimation of the location of data) is one of the most commonly used procedures in neuroscience and the basic procedure for obtaining event-related potentials (ERP). Only the arithmetic mean is routinely used in the current practice of ERP research, though its sensitivity to outliers is well-known. Weighted averaging is sometimes used as a more robust procedure, however, it can be not sufficiently appropriate when the signal is nonstationary within a trial. Trimmed estimators provide an alternative way to average data. In this paper, a number of such location estimators (trimmed mean, Winsorized mean and recently introduced trimmed L-mean) are reviewed, as well as arithmetic mean and median. A new robust location estimator tanh, which allows the data-dependent optimization, is proposed for averaging of small number of trials. The possibilities to improve signal-to-noise ratio (SNR) of averaged waveforms using trimmed location estimators are demonstrated for epochs randomly drawn from a set of real auditory evoked potential data.

Adult↗
PubMed2004

Non-stationary time series and the robustness of circadian rhythms.

Circadian rhythms are regular oscillations in the value of behavioral and physiological variables of organisms that recur on a daily basis. The purpose of this study was to evaluate the extent of non-stationarity of circadian rhythms over several days, to determine how damaging is the violation of the assumption of stationarity in the analysis of circadian rhythms, and to formalize the concept of "rhythm robustness" as an index of oscillatory ("weak") stationarity. Simulated (computer-generated) and experimental data sets (rhythms of body temperature and running-wheel activity in several rodent species) were analysed. Tests of stationarity based on the variance of the daily means and the variance of the daily variances revealed that most experimental data sets are not stationary. Analysis of linear trends indicated that significant trends are rare in experimental data sets. Although the non-stationarity of the experimental data sets reduced the spectral energy of the Enright periodogram used to assess rhythmicity, detection of circadian rhythmicity was not prevented in any of the rhythmic data sets. The results of the various analyses allow the inference that, after high-frequency noise is filtered out, the value of the periodogram's Q(P) statistic reflects the extent of stationarity of the time series. Thus, the "robustness" of a circadian rhythm (i.e. the magnitude of the empirical Q(P) value as compared to the Q(P) value associated with a perfectly rhythmic time series) can serve as an index of the stationarity of the rhythm.

Analysis of Variance↗
PubMed2005

Model for the robust establishment of precise proportions in the early Drosophila embryo.

During embryonic development, a spatial pattern is formed in which proportions are established precisely. As an early pattern formation step in Drosophila embryos, an anterior-posterior gradient of Bicoid (Bcd) induces hunchback (hb) expression (Nature 337 (1989) 138; Nature 332 (1988) 281). In contrast to the Bcd gradient, the Hb profile includes information about the scale of the embryo. Furthermore, the resulting hb expression pattern shows a much lower embryo-to-embryo variability than the Bcd gradient (Nature 415 (2002) 798). An additional graded posterior repressing activity could theoretically account for the observed scaling. However, we show that such a model cannot produce the observed precision in the Hb boundary, such that a fundamentally different mechanism must be at work. We describe and simulate a model that can account for the observed precise generation of the scaled Hb profile in a highly robust manner. The proposed mechanism includes Staufen (Stau), an RNA binding protein that appears essential to precision scaling (Nature 415 (2002) 798). In the model, Stau is released from both ends of the embryo and relocalizes hb RNA by increasing its mobility. This leads to an effective transport of hb away from the respective Stau sources. The balance between these opposing effects then gives rise to scaling and precision. Considering the biological importance of robust precision scaling and the simplicity of the model, the same principle may be employed more often during development.

Animals↗
PubMed2005

Robust and efficient design of experiments for the Monod model.

In this paper the problem of designing experiments for the Monod model, which is frequently used in microbiology, is studied. The model is defined implicitly by a differential equation and has numerous applications in microbial growth kinetics, environmental research, pharmacokinetics, and plant physiology. The designs presented so far in the literature are local optimal designs, which depend sensitively on a preliminary guess of the unknown parameters, and are for this reason in many cases not robust with respect to their misspecification. Uniform designs and maximin optimal designs are considered as a strategy to obtain robust and efficient designs for parameter estimation. In particular, standardized maximin D- and E-optimal designs are determined and compared with uniform designs, which are usually applied in these microbiological models. It is demonstrated that maximin optimal designs are substantially more efficient than uniform designs. Parameter variances can be decreased by a factor of two by simply sampling at optimal times during the experiment. Moreover, the maximin optimal designs usually provide the possibility for the experimenter to check the model assumptions, because they have more support points than parameters in the Monod model.

Bacteria↗
PubMed2006

Application of "robust" methods to the analysis of collaborative trial data using bacterial colony counts.

We describe techniques for the application of two methods, robust to the presence of "outliers", to the hierarchical analysis of variance of bacterial count data from collaborative trials. The techniques are tested against both artificially-generated data with known distributional parameters and actual trial results containing outliers. The relative merits of the robust methods are discussed in comparison with conventional ANOVA techniques.

Analysis of Variance↗
PubMed2006

Robust prescan calibration for multiple spin-echo sequences: application to FSE and b-SSFP.

The collection of fast imaging techniques that use multiple spin-echo (MSE) sequences relies on a precise phase relationship between spin echoes and stimulated echoes that form along the radiofrequency refocusing pulse train. Failure to achieve this condition produces dark banding artifacts that result from destructive interference between signal coherence pathways. Satisfying this condition on the microsecond timescale required is technically challenging for conditions involving strong diffusion-weighted gradients, for arbitrary orientation acquisitions and at large field strengths with high-resolution acquisitions. Two clinically significant MSE sequences, fast spin echo (FSE) and balanced steady-state free precession (b-SSFP), are investigated in this work using a 4-T whole-body scanner. We developed a readout-projection-based prescan technique that ensures coherent signal formation by utilizing banding artifacts to automatically adjust gradient balance. Subsequent image acquisition using the results of this prescan permits the formation of coherent-echo images, which are robust under challenging imaging conditions. The robustness of this approach is demonstrated for FSE and b-SSFP images obtained from the knees of human volunteers. We believe that the use of this prescan calibration technique for the alignment of signal pools in MSE sequences is critical at high fields and will facilitate the implementation of high-quality clinically significant sequences such as FSE and b-SSFP.

Artifacts↗
PubMed2005

Energy efficient and robust rhythmic limb movement by central pattern generators.

Humans show great energy efficiency and robustness in rhythmic tasks, such as walking and arm swinging. In this study a mathematical model of rhythmic limb movement is presented, which shows that tight local coupling of Central Pattern Generators (CPGs) to limbs could explain part of this behavior. Afferent feedback to flexor and extensor centers of the CPG is crucial in providing energy efficiency by means of resonance tuning. Feedback of positional information provides resonance tuning above the endogenous frequency of the CPG. Integral feedback provides resonance tuning at and below the endogenous frequency. Feedback of velocity information is necessary to compensate for the time delay in the loop, coupling limb to CPG; without velocity feedback bi-stability occurs and resonance tuning is not possible at high movement frequencies. The concepts of energy efficient and robust control of rhythmic limb movements are also applicable to robotics. It is the first CPG model, which provides resonance tuning at natural limb frequencies above and below its endogenous frequency.

Brain↗
PubMed2004

Fast and robust registration of PET and MR images of human brain.

In recent years, mutual information has proved to be an excellent criterion for registration of intra-individual images from different modalities. Multi-resolution coarse-to-fine optimization was proposed for speeding-up of the registration process. The aim of our work was to further improve registration speed without compromising robustness or accuracy. We present and evaluate two procedures for co-registration of positron emission tomography (PET) and magnetic resonance (MR) images of human brain that combine a multi-resolution approach with an automatic segmentation of input image volumes into areas of interest and background. We show that an acceleration factor of 10 can be achieved for clinical data and that a suitable preprocessing can improve robustness of registration. Emphasis was laid on creation of an automatic registration system that could be used routinely in a clinical environment. For this purpose, an easy-to-use graphical user interface has been developed. It allows physicians with no special knowledge of the registration algorithm to perform a fast and reliable alignment of images. Registration progress is presented on the fly on a fusion of images and enables visual checking during a registration.

Algorithms↗
PubMed2006

Shunting inhibition improves robustness of gamma oscillations in hippocampal interneuron networks by homogenizing firing rates.

Networks of GABAergic neurons are key elements in the generation of gamma oscillations in the brain. Computational studies suggested that the emergence of coherent oscillations requires hyperpolarizing inhibition. Here, we show that GABA(A) receptor-mediated inhibition in mature interneurons of the hippocampal dentate gyrus is shunting rather than hyperpolarizing. Unexpectedly, when shunting inhibition is incorporated into a structured interneuron network model with fast and strong synapses, coherent oscillations emerge. In comparison to hyperpolarizing inhibition, networks with shunting inhibition show several advantages. First, oscillations are generated with smaller tonic excitatory drive. Second, network frequencies are tuned to the gamma band. Finally, robustness against heterogeneity in the excitatory drive is markedly improved. In single interneurons, shunting inhibition shortens the interspike interval for low levels of drive but prolongs it for high levels, leading to homogenization of neuronal firing rates. Thus, shunting inhibition may confer increased robustness to gamma oscillations in the brain.

Animals↗
PubMed2005

Robust treatment planning for intensity modulated radiotherapy of prostate cancer based on coverage probabilities.

BACKGROUND AND PURPOSE: To evaluate an optimization approach where coverage probabilities are incorporated into the optimization of intensity modulated radiotherapy (IMRT) to overcome the problem of margin definition in the case of overlapping planning target volume and organs at risk. PATIENTS AND METHODS: IMRT plans were generated for three optimization approaches: based on a planning CT plus margin (A), on prostate and rectum contours from five pre-treatment CT plus margin (B), and on coverage probabilities (C). For approach (C), the probability of organ occupation was computed for each voxel from five pre-treatment CTs and the population distribution of systematic setup error and it was used as local weight in the costfunctions. Monte Carlo simulations of treatment courses were used to compute the probability distribution of prostate and rectal wall equivalent uniform dose (EUD). RESULTS: Treatment simulations showed best and most robust results for prostate and rectal wall EUD within the population for (C). For (A) the rectal wall EUD was on average about 1.5 Gy greater than in (C), while the prostate EUD was lower than those from (C) for most of the patients for (B) (especially for those with great organ motion). CONCLUSIONS: The incorporation of coverage probabilities as local weights allows for dose escalation as well as improved rectal sparing and results in a safer and more robust IMRT treatment.

Computer Simulation↗
PubMed2005

Home INR monitoring of oral anticoagulant therapy in children using the CoaguChek S point-of-care monitor and a robust education program.

INTRODUCTION: Management strategies such as self-monitoring of anticoagulant therapy have been reported with increased frequency. Whilst patient education is frequently mentioned, details regarding the educational interventions employed are scarce. This study aimed to improve the outcomes of home monitoring of warfarin therapy in children through the development and implementation of a robust intervention, based upon the PRECEDE model of education. MATERIALS AND METHODS: Participating parents had to complete an intensive education and training program. After demonstrating practical and theoretical competency, parents commenced home monitoring. Every second scheduled home INR (H-INR) required a paired INR on the same day, obtained by a trained pathology collector (C-INR). Demographic and statistical outcome data was collected. RESULTS: Parental understanding of warfarin therapy improved significantly following the educational intervention (p<0.0001). 65.5% of H-INRs and 64.4% of C-INRs were within the target range (ns). Lin's correlation coefficient between H-INRs and C-INRs was 0.949. There were no warfarin-related adverse events. CONCLUSION: This study demonstrated a significant improvement in parental knowledge following participation in a robust educational intervention. Furthermore, compared to previous reports in children, a greater level of correlation between home and hospital-based INRs was achieved by participating parents. The use of similar educational interventions may serve to improve the outcomes of similar management strategies.

Administration, Oral↗
PubMed2006

Glucagon challenge in the rat: a robust method for the in vivo assessment of Glycogen phosphorlyase inhibitor efficacy.

INTRODUCTION: Glycogen phosphorlyase inhibitors (GPi) act on the glycogenolytic pathway decreasing hepatic glucose output, making them potential candidates for Type 2 diabetes treatment. We established a robust in vivo method to assess GPis efficacy utilising glucagon-stimulated glycogenolysis. METHODS: Blood glucose was monitored in both male AP Wistar and AP Zucker rats using tail prick samples pre- and post intraperitoneal or subcutaneous glucagon administration. The effect of glycogen phosphorylase inhibitors GPi296 (6-60 mg kg(-1) po) and DAB (5 mg kg(-1) po) upon glucose response to subcutaneous glucagon were examined in both strains. RESULTS: In the Wistar rat glucagon induced dose related increases in blood glucose, with the maximum increase occurring 20 min post dose (4.0+/-0.88 mmol l(-1), intraperitoneal; and 2.8+/-0.72 mmol l(-1), subcutaneous, ns). Intraperitoneal glucagon administration produced shorter duration blood glucose elevation than observed with the subcutaneous route of administration. In the Zucker rat, no differences were observed between the 10 and 13 week old rats in response to glucagon (3-200 microg kg(-1) subcutaneous). The maximum blood glucose increase was lower in the Wistar rat compared to the Zucker rats (2.9+/-0.20 vs 7.7+/-1.22 mmol l(-1), P<0.0000018). GPi296 and DAB both produced similar inhibition in each strain. DISCUSSION: Subcutaneous glucagon administration induced more sustained increases in blood glucose than intraperitoneal administration. Blood glucose response to glucagon was higher in the Zucker rat compared to the Wistar rat; there was no difference in inhibition mediated by either GPi296 or DAB between the two strains. We believe that subcutaneous glucagon administration produces a robust model for the assessment of GPis in either rat strain.

Animals↗
PubMed2005

Assessing statistical precision, power, and robustness of alternative experimental designs for two color microarray platforms based on mixed effects models.

Recommendations on experimental designs for two color microarray systems have been generally conflicting as they pertain to the general choice between reference and non-reference loop designs. This conflict may currently exist because many previously published assessments may not have effectively connected design layout with the level of biological relative to technical replication. We reassess various reference and non-reference designs for statistical efficiency in terms of standard errors of mean differences, power of test, and robustness using recently developed mixed model software tools. In minimally replicated cases (n = 2), it appears that the reference design outperforms the classical loop design whereby a sample from each animal is used for only one particular array hybridization. Alternatively, the reference design was consistently inferior to those connected loop designs in which a sample from each animal is used in two different hybridizations. Nevertheless, the gap in power between these two designs diminished as the biological to residual variance ratio increased. The statistical efficiency of a single large classical loop design for the comparison of many treatments was demonstrated to be highly sensitive to missing arrays relative to a common reference design (n = 2). However, the use of two loops within an interwoven loop design was shown to be substantially more robust to missing arrays and statistically more efficient relative to a common reference design. Furthermore, the use of more than one loop leads to less disparity in precision and power comparisons between any two treatments.

Animals↗
PubMed2004

Multiple feedback loops are key to a robust dynamic performance of tryptophan regulation in Escherichia coli.

Living systems must adapt quickly and stably to uncertain environments. A common theme in cellular regulation is the presence of multiple feedback loops in the network. An example of such a feedback structure is regulation of tryptophan concentration in Escherichia coli. Here, three distinct feedback mechanisms, namely genetic regulation, mRNA attenuation and enzyme inhibition, regulate tryptophan synthesis. A pertinent question is whether such multiple feedback loops are "a case of regulatory overkill, or do these different feedback regulators have distinct functions?" Another moot question is how robustness to uncertainties can be achieved structurally through biological interactions. Correlation between the feedback structure and robustness can be systematically studied by tools commonly employed in feedback theory. An analysis of feedback strategies in the tryptophan system in E. coli reveals that the network complexity arising due to the distributed feedback structure is responsible for the rapid and stable response observed even in the presence of system uncertainties.

Computer Simulation↗
PubMed2000

Robust PID tuning strategy for uncertain plants based on the Kharitonov theorem

In this paper, the Kharitonov theorem for interval plants is exploited for the purpose of synthesizing a stabilizing controller. The aim here is to develop a controller to simultaneously stabilize the four Kharitonov-defined vortex polynomials. Different from the prevailing works, the controller is designed systematically and graphically through the search of a non-conservative Kharitonov region in the controller coefficient parameter plane. The region characterizes all stabilizing PID controllers that stabilize an uncertain plant. Thus the relationship between the Kharitonov region and the stabilizing controller parameters is manifest. Extensively, to further guarantee the system with certain robust safety margins, a virtual gain phase margin tester compensator is added. Stability analysis is carried out. The control system is proved to maintain robustness at least to the pre-specified margins. The synthesized controller with coefficients selected from the obtained non-conservative Kharitonov region can stabilize the concerned uncertain plants and fulfill system specifications in terms of gain margins and phase margins.

Journal Article↗
PubMed2001

Robust control for a class of time varying systems via switching hypersurface design with output signals.

Sliding mode control methods have been used widely since they provide robustness against parameter variations and disturbances. This paper focuses on the problem of a robust output-sliding control design for linear uncertain multi-input multi-output time-varying systems with norm-bounded uncertainty. Output signals are used for the definition of switching hypersurfaces. The formulation of a control law is emphasized. Output tracking can be achieved against a class of time varying parameter variations and external disturbances. The effectiveness of the proposed output-sliding control is confirmed by an application example.

Journal Article↗
PubMed2006

A simple method to find a robust output feedback controller by random search approach.

This paper presents a simple but effective method for finding a robust output feedback controller via a random search algorithm. The convergence of this algorithm can be guaranteed. Moreover, the probability to find a solution as well as the number of random trials can be estimated. The robustness of the closed-loop system is improved by the minimization of a given cost function reflecting the performance of the controller for a set of plants. Simulation studies are used to demonstrate the effectiveness of the proposed method.

Journal Article↗