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PubMed1988

Alleged synapomorphy of the M1/I1 eruption pattern in robust australopithecines and Homo: evidence from high-resolution computed tomography.

Ever since Broom and Robinson (1951) published their claim that the eruption pattern of permanent incisors in robust australopithecines was most similar to that of modern man and different from that of gracile australopithecines and apes, the accuracy of this observation has been the subject of periodic debate (e.g., Wallace: Ph.D. thesis, 1972; Dean: Am. J. Phys. Anthropol. 67:251-257, 1985; Grine: Am. J. Phys. Anthropol. 72:353-359, 1987). Part of the problem is that the developing incisors in one of the specimens most crucial to this argument (SK61) are difficult to visualize clearly by conventional radiographic techniques because of the heavy mineralization in the fossil. This study reanalyzes SK 61 by high-resolution computed tomography in order to contribute to the final resolution of its incisor development. Grine's (op. cit.) assessment of the incisors as the deciduous ones, not the permanent ones, is fully confirmed. This fact, in conjunction with the observation that permanent incisor root formation had only just commenced in this specimen, further weakens the argument of M1/I1 eruption pattern synapomorphy between Homo and robust australopithecines.

Fossils↗
PubMed2006

Effect of mobility on femur midshaft external shape and robusticity.

This study investigates differences in femur midshaft shape, robusticity, and sexual dimorphism derived from external measurements between a broad range of prehistoric and historic North American populations with different subsistence strategies and inferred levels of mobility. The sample was divided into six groups to test whether observed femur midshaft variables follow the patterns predicted based on archaeologically and historically determined subsistence and mobility data. The results suggest significant variation in femur midshaft shape and robusticity in all populations, and that inferred mobility levels do not correspond consistently with femur midshaft structure in either males or females. Results do, however, support the prediction that sexual dimorphism is generally greater in more mobile populations.

Anthropology, Cultural↗
PubMed2006

The robustness of the transcriptional response to alterations in morphogenetic gradients.

Sharp sigmoidal transitions of transcription in response to morphogenetic gradients are often involved in the generation of boundaries during development. Here we explore two simple models of transcription that generate sigmoidal outputs. Specifically, we analyse the case of a promoter responding to a single type of activator. We then consider a model where an activator and an inhibitor, distributed as two gradients with opposite slopes, act competitively on the same promoter. This system can produce a sharper response than that obtained with a promoter with the same number of binding sites responding to a similar gradient of activator alone. We also explore how these systems buffer the effect of variations in the dosage of the morphogens. Our results highlight how non-linearities can be a source of robustness and the crucial role of the inhibitor in the generation of a sharp and robust response.

Animals↗
PubMed2005

Robust scale-up of dead end filtration: impact of filter fouling mechanisms and flow distribution.

Robust design of a dead end filtration step and the resulting performance at manufacturing scale relies on laboratory data collected with small filter units. During process development it is important to characterize and understand the filter fouling mechanisms of the process streams so that an accurate assessment can be made of the filter area required at manufacturing scale. Successful scale-up also requires integration of the lab-scale filtration data with an understanding of flow characteristics in the full-scale filtration equipment. A case study is presented on the development and scale-up of a depth filtration step used in a 2nd generation polysaccharide vaccine manufacturing process. The effect of operating parameters on filter performance was experimentally characterized for a diverse set of process streams. Filter capacity was significantly reduced when operating at low fluxes, caused by both low filtration pressure and high stream viscosity. The effect of flux on filter capacity could be explained for a variety of diverse streams by a single mechanistic model of filter fouling. To complement the laboratory filtration data, the fluid flow and distribution characteristics in manufacturing-scale filtration equipment were carefully evaluated. This analysis identified the need for additional scale-up factors to account for non-uniform filter area usage in large-scale filter housings. This understanding proved critical to the final equipment design and depth filtration step definition, resulting in robust process performance at manufacturing scale.

Biological Products↗
PubMed2001

Power and robustness of a score test for linkage analysis of quantitative traits using identity by descent data on sib pairs.

Identification of genes involved in complex traits by traditional (lod score) linkage analysis is difficult due to many complicating factors. An unfortunate drawback of non-parametric procedures in general, though, is their low power to detect genetic effects. Recently, Dudoit and Speed [2000] proposed using a (likelihood-based) score test for detecting linkage with IBD data on sib pairs. This method uses the likelihood for theta, the recombination fraction between a trait locus and a marker locus, conditional on the phenotypes of the two sibs to test the null hypothesis of no linkage (theta = (1/2)). Although a genetic model must be specified, the approach offers several advantages. This paper presents results of simulation studies characterizing the power and robustness properties of this score test for linkage, and compares the power of the test to the Haseman-Elston and modified Haseman-Elston tests. The score test is seen to have impressively high power across a broad range of true and assumed models, particularly under multiple ascertainment. Assuming an additive model with a moderate allele frequency, in the range of p = 0.2 to 0.5, along with heritability H = 0.3 and a moderate residual correlation rho = 0.2 resulted in a very good overall performance across a wide range of trait-generating models. Generally, our results indicate that this score test for linkage offers a high degree of protection against wrong assumptions due to its strong robustness when used with the recommended additive model.

Computer Simulation↗
PubMed1989

A more powerful robust sib-pair test of linkage for quantitative traits.

A more powerful robust test for linkage is developed from the methodology of Haseman and Elston [Behav Genet 2(1):3-19, 1972]. This new robust test uses weighted least-squares (WLS) methods to detect linkage between a quantitative trait and a polymorphic marker. For comparison, the characteristics of a test for linakge that uses known trait genotypes for the parents are also studied. Sample sizes needed to detect linkage, calculated using asymptotic results, are compared for 1) the usual Haseman-Elston method, 2) the WLS method, and 3) the method that uses parental trait genotype data. The WLS method needs at most twice the number of sib pairs as does the method that uses information on the trait genotypes of the parents. The small sample properties of the Haseman-Elston (H-E) and WLS tests are investigated by simulation. The power calculations for the H-E method are found to be accurate. The power of the WLS method is overestimated when fewer than 300 sib pairs are studied, but the WLS method is nonetheless more powerful than the usual H-E method. In samples of fewer than 300 sib pairs, the WLS test tends to be anticonservative. Treating all sib pairs from sibships of size 3 or 5 as independent does not increase the significance of the tests.

Alleles↗
PubMed1994

Robust genetic linkage analysis based on a score test of homogeneity: the weighted pairwise correlation statistic.

In testing genetic linkage using large or complex pedigrees, robust methods may be preferred to the Lod-score method. The affected-pedigree-member method is robust but does not use the information available in nonaffected subjects, which results in a loss of power. We propose a new test of genetic linkage based on a score test of homogeneity derived from a random effect model. The statistic is simple and uses only pairs of subjects. In contrast with the affected-pedigree-method, it uses all the available pairs and does not depend on the marker alleles frequencies. A rank version of this weighted pairwise correlation statistic is proposed, its exact first and second moment derived. We show that for age-dependent diseases, it provides a simple nonparametric test.

Age of Onset↗
PubMed2005

Robust ascertainment-adjusted parameter estimation.

Nonrandom ascertainment is commonly used in genetic studies of rare diseases, since this design is often more convenient than the random-sampling design. When there is an underlying latent heterogeneity, Epstein et al. ([2002] Am. J. Hum. Genet. 70:886-895) showed that it is possible to get unbiased or consistent estimation of population parameters under ascertainment adjustment, but Glidden and Liang ([2002] Genet. Epidemiol. 23:201-208) showed in a simulation study that the resulting estimates are highly sensitive to misspecification of the latent components. To overcome this difficulty, we consider a heavy-tailed model for latent variables that allows a robust estimation of the parameters. We describe a hierarchical-likelihood approach that avoids the integration used in the standard marginal likelihood approach. We revisit and extend the previous simulation, and show that the resulting estimator is efficient and robust against misspecification of the distribution of latent variables.

Genetic Diseases, Inborn↗
PubMed2003

Robust Bayesian estimation of the hemodynamic response function in event-related BOLD fMRI using basic physiological information.

In BOLD fMRI data analysis, robust and accurate estimation of the Hemodynamic Response Function (HRF) is still under investigation. Parametric methods assume the shape of the HRF to be known and constant throughout the brain, whereas non-parametric methods mostly rely on artificially increasing the signal-to-noise ratio. We extend and develop a previously proposed method that makes use of basic yet relevant temporal information about the underlying physiological process of the brain BOLD response in order to infer the HRF in a Bayesian framework. A general hypothesis test is also proposed, allowing to take advantage of the knowledge gained regarding the HRF to perform activation detection. The performances of the method are then evaluated by simulation. Great improvement is shown compared to the Maximum-Likelihood estimate in terms of estimation error, variance, and bias. Robustness of the estimators with regard to the actual noise structure or level, as well as the stimulus sequence, is also proven. Lastly, fMRI data with an event-related paradigm are analyzed. As suspected, the regions selected from highly discriminating activation maps resulting from the method exhibit a certain inter-regional homogeneity in term of HRF shape, as well as noticeable inter-regional differences.

Adult↗
PubMed2002

Sequential robust design methodology and X-ray photoelectron spectroscopy to analyze the grafting of hyaluronic acid to glass substrates.

Sequential Robust Design experiments and X-ray photoelectron spectroscopic (XPS) studies were performed to examine the immobilization of hyaluronic acid (HA) on glass substrates chemisorbed with N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane (EDS). Numerous reaction conditions were investigated, including the concentrations of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride (EDC), N-hydroxysulfosuccinimide (Sulfo-NHS), and HA, and the reaction buffer type, concentration, and pH. The elemental surface compositions of carbon and silicon (C/Si ratio) were used to assess the extent of HA immobilization, leading to the identification of critical HA-binding reaction conditions and the determination of an optimum surface chemistry. The optimum chemistry consisted of 200 mM EDC, 50 mM Sulfo-NHS, 10 mM N-(2-hydroxyethyl)piperazine-N'-(2-ethanesulfonic acid) (HEPES) buffer at a pH of 7.0, and 3 mg/mL HA. This work emphasizes the advantages of using Robust Design methods over traditional statistical experimental design, particularly when large numbers of variables are examined and costly analytical techniques are employed.

Adhesiveness↗
PubMed2002

Design and constraints of the Drosophila segment polarity module: robust spatial patterning emerges from intertwined cell state switches.

The Drosophila segment polarity genes constitute the last tier in the segmentation cascade; their job is to maintain the boundaries between parasegments and provide positional "read-outs" within each parasegment for the entire developmental history of the animal. These genes constitute a relatively well-defined network with a relatively well-understood patterning task. In a previous publication (von Dassow et al. 2000. Nature 406:188-192) we showed that a computer model predicts the segment polarity network to be a robust boundary-making device. Here we elaborate those findings. First, we explore the constraints among parameters that govern the network model. Second, we test architectural variants of the core network, and show that the network tolerates a wide variety of adjustments in design. Third, we evaluate several topologically identical models that incorporate more or less molecular detail, finding that more-complex models perform noticeably better than simplified ones. Fourth, we discuss two instances in which the failure of the network model to behave in a life-like fashion highlights mechanistic details that need further experimental investigation. We conclude with an explanation of how the segment polarity network can be understood as an interwoven conspiracy of simple dynamical elements, several bistable switches and a homeostat. The robustness with which the network as a whole maintains a spatial regime of stable cell state emerges from generic dynamical properties of these simple elements.

Animals↗
PubMed2004

Robust field map generation using a triple-echo acquisition.

PURPOSE: To establish a fast and robust technique for generating magnetic field maps for the correction of geometric distortions in echo-planar magnetic resonance (MR) images. MATERIALS AND METHODS: Multislice gradient-echo (GE) images were acquired at echo times of 6, 6.5, and 7.5 msec in order to cover a field shift range of +/-666 Hz in the resulting B0 maps. To account for possible phase wrap scenarios, seven phase triples were calculated for each pixel. Linear regression of the phase vs. echo time was performed for each set. The slope of the set with the minimum fitting error was taken as the true magnetic field in the respective pixel. RESULTS: Based on the fitting error distribution, the technique is shown to be feasible and effective for assessing the field distribution in the brain at 3 T, especially in inferior brain areas (amygdalae, hippocampus). Examples of echo-planar images distortion corrected using the calculated field maps are shown. CONCLUSION: The approach presented yields robust estimation of magnetic field maps and requires under a minute of additional acquisition time and only seconds of computational time. As such, it is easily possible to apply image distortion correction in routine functional MR imaging (fMRI) studies, enabling improved coregistration of brain activation maps with structures on anatomical images.

Algorithms↗
PubMed2006

Two-dimensional reverse phase-reverse phase chromatography: A simple and robust platform for sensitive quantitative analysis of peptides by LC/MS. Hardware design.

We have revised current two-dimensional RP-RP approaches and developed a new robust 2-D RP-RP platform. This platform was implemented on an Agilent 1100 2-D liquid chromatography system and is based on high pressure switching between two high-resolution RP columns. An independent binary gradient was implemented for each dimension. The powerful combination of dual analytical columns with independent gradient elution achieves high analyte purity, effectively eliminates matrix effects, and maximizes MS sensitivity in Q1 SIM comparable to the sensitivity enhancements of MS/MS-based methods. Implementation of dual simultaneous gradient profiles (overlapped gradients) reduces 2-D method run-time to the scale of 1-D method run-times. This robust and sensitive approach is particularly suitable for hydrophobic peptides and small proteins and can be used as a routine standard technique for enhanced on-line peptide purification coupled with mass spectrometric detection.

C-Peptide↗
PubMed2005

A robust clustering approach for NMR spectra of natural product extracts.

A robust method was developed to cluster similar NMR spectra from partially purified extracts obtained from a range of marine sponges and a plant biota. The NMR data were acquired using microtiter plate NMR (VAST) in protonated solvents. A sample data set which contained several clusters was used to optimize the protocol. The evaluation of the robustness was performed using three different clustering methods: tree clustering analysis, K-means clustering and multidimensional scaling. These methods were compared for consistency using the sample data set and the optimized methodology was applied to clustering of a set of spectra from partially purified biota extracts.

Animals↗
PubMed1995

Computerized consensus diagnosis: a classification strategy for the robust analysis of MR spectra. I. Application to 1H spectra of thyroid neoplasms.

We introduce and apply a new classification strategy we call computerized consensus diagnosis (CCD). Its purpose is to provide robust, reliable classification of biomedical data. The strategy involves the cross-validated training of several classifiers of diverse conceptual and methodological origin on the same data, and appropriately combining their outcomes. The strategy is tested on proton magnetic resonance spectra of human thyroid biopsies, which are successfully allocated to normal or carcinoma classes. We used Linear Discriminant Analysis, a Neural Net-based method, and Genetic Programming as independent classifiers on two spectral regions, and chose the median of the six classification outcomes as the consensus. This procedure yielded 100% specificity and 100% sensitivity on the training sets, and 100% specificity and 98% sensitivity on samples of known malignancy in the test sets. We discuss the necessary steps any classification approach must take to guarantee reliability, and stress the importance of fuzziness and undecidability in robust classification.

Adenocarcinoma, Follicular↗
PubMed2005

RESTORE: robust estimation of tensors by outlier rejection.

Signal variability in diffusion weighted imaging (DWI) is influenced by both thermal noise and spatially and temporally varying artifacts such as subject motion and cardiac pulsation. In this paper, the effects of DWI artifacts on estimated tensor values, such as trace and fractional anisotropy, are analyzed using Monte Carlo simulations. A novel approach for robust diffusion tensor estimation, called RESTORE (for robust estimation of tensors by outlier rejection), is proposed. This method uses iteratively reweighted least-squares regression to identify potential outliers and subsequently exclude them. Results from both simulated and clinical diffusion data sets indicate that the RESTORE method improves tensor estimation compared to the commonly used linear and nonlinear least-squares tensor fitting methods and a recently proposed method based on the Geman-McClure M-estimator. The RESTORE method could potentially remove the need for cardiac gating in DWI acquisitions and should be applicable to other MR imaging techniques that use univariate or multivariate regression to fit MRI data to a model.

Algorithms↗
PubMed2006

Protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster: large-scale organization and robustness.

High-throughput screens have begun to reveal protein interaction networks in several organisms. To understand the general properties of these protein interaction networks, a systematic analysis of topological structure and robustness was performed on the protein interaction networks of Saccharomyces cerevisiae, Caenorhabditis elegans and Drosophila melanogaster. It shows that the three protein interaction networks have a scale-free and high-degree clustering nature as the consequence of their hierarchical organization. It also shows that they have the small-world property with similar diameter at 4-5. Evaluation of the consequences of random removal of both proteins and interactions from the protein interaction networks suggests their high degree of robustness. Simulation of a protein's removal shows that the protein interaction network's error tolerance is accompanied by attack vulnerability. These fundamental analyses of the networks might serve as a starting point for further exploring complex biological networks and the coming research of "systems biology".

Algorithms↗
PubMed2003

Robustness and power of analysis of covariance applied to ordinal scaled data as arising in randomized controlled trials.

In clinical trials comparing two treatments, ordinal scales of three, four or five points are often used to assess severity, both prior to and after treatment. Analysis of covariance is an attractive technique, however, the data clearly violate the normality assumption and in the presence of small samples, and large sample theory may not apply. The robustness and power of various versions of parametric analysis of covariance applied to small samples of ordinal scaled data are investigated through computer simulation. Subjects are randomized to one of two competing treatments and the pre-treatment, or baseline, assessment is used as the covariate. We compare two parametric analysis of covariance tests that vary according to the treatment of the homogeneity of regressions slopes and the two independent samples t-test on difference scores. Under the null hypothesis of no difference in adjusted treatment means, we estimated actual significance levels by comparing observed test statistics to appropriate critical values from the F- and t-distributions for nominal significance levels of 0.10, 0.05, 0.02 and 0.01. We estimated power by similar comparisons under various alternative hypotheses. The model which assumes homogeneous slopes and the t-test on difference scores were robust in the presence of three, four and five point ordinal scales. The hierarchical approach which first tests for homogeneity of regression slopes and then fits separate slopes if there is significant non-homogeneity produced significance levels that exceeded the nominal levels especially when the sample sizes were small. The model which assumes homogeneous regression slopes produced the highest power among competing tests for all of the configurations investigated. The t-test on difference scores also produced good power in the presence of small samples.

Analysis of Variance↗