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Dopamine as a robust anchor to immobilize functional molecules on the iron oxide shell of magnetic nanoparticles.

We report on the use of dopamine (DA) as a robust molecular anchor to link functional molecules to the iron oxide shell of magnetic nanoparticles. Using nitrilotriacetic acid (NTA) as the functional molecule, we created a system with an M/Fe2O3-DA-NTA (M = Co or SmCo5.2) nanostructure, which possesses high stability and specificity for separating histidine-tagged proteins. The well-established biocompatibility of iron oxide and the robust covalent bonds between DA and Fe2O3 render this strategy attractive for constructing biofunctional magnetic nanoparticles containing iron oxide.

Dopamine↗

Median-based robust regression methods in prediction of drug stability.

The classical isothermal approach for the prediction of drug stability exploits least squares regression. In this paper the use of some robust regression techniques to estimate the rate constants at different temperatures has been evaluated. These techniques are able to give accurate estimates when data are contaminated by the presence of outliers. The successful application of two robust methods, single median and repeated median, to real stability data from the literature is shown. Moreover, the authors have modified the original methods in order to apply them to data sets with replicates, typical of stability studies. The performances of the modified techniques have been investigated with simulated data sets containing outliers and with real data. They appear suitable for preliminary stability studies, especially on solid dosage forms. For a quick implementation of these methods, macroprograms written for a widely used spreadsheet are reported.

Computer Simulation↗

Robust representations for faces: evidence from visual search.

We report evidence from visual search that people can develop robust representations for highly overlearned faces. When observers searched for their own face versus the face of an unfamiliar observer, search slopes and intercepts revealed consistently faster processing of self than stranger. These processing advantages persisted even after hundreds of presentations of the unfamiliar face and even for atypical profile and upside-down views. Observers not only showed rapid asymptotic recognition of their own face as the target, but could reject their own face more quickly as the distractor. These findings suggest that robust representations for a highly overlearned face may (a) mediate rapid asymptotic visual processing, (b) require extensive experience to develop, (c) contain abstract or view-invariant information, (d) facilitate a variety of processes such as target recognition and distractor rejection, and (e) demand less attentional resources.

Adolescent↗

Robust recollection rejection in the memory conjunction paradigm.

The present research provides compelling evidence for recollection rejection in the memory conjunction paradigm. In Experiment 1, warnings provided at time of test were shown to reduce memory conjunction errors. Moreover, the authors found substantial evidence of recollection rejection and phantom recollection. In Experiment 2, the authors manipulated how often study items were presented. Participants were told that they could earn a cash payoff for being accurate. Recognition of conjunction lures was lower in the multiple presentation condition. However, the payoff manipulation did not significantly interact with item type. The authors obtained evidence of robust recollection rejection from 3 different dependent measures. Consistent with Experiment 1, they also found evidence of phantom recollection. These findings provide evidence that recollection rejection can be quite robust in the memory conjunction paradigm.

Attention↗

Comparing several robust tests of stochastic equality with ordinally scaled variables and small to moderate sized samples.

In a comparison of 2 treatments, if outcome scores are denoted by X in 1 condition and by Y in the other, stochastic equality is defined as P(X < Y) = P(X > Y). Tests of stochastic equality can be affected by characteristics of the distributions being compared, such as heterogeneity of variance. Thus, various robust tests of stochastic equality have been proposed and are evaluated here using a Monte Carlo study with sample sizes ranging from 10 to 30. Three robust tests are identified that perform well in Type I error rates and power except when extremely skewed data co-occur with very small n. When tests of stochastic equality might be preferred to tests of means is also considered.

Humans↗

Robust and optimal use of information in stereo vision.

Differences between the left and right eye's views of the world carry information about three-dimensional scene structure and about the position of the eyes in the head. The contemporary Bayesian approach to perception implies that human performance in using this source of eye-position information can be analysed most usefully by comparison with the performance of a statistically optimal observer. Here we argue that the comparison observer should also be statistically robust, and we find that this requirement leads to qualitatively new behaviours. For example, when presented with a class of stereoscopic stimuli containing inconsistent information about eccentricity of gaze, estimates of this gaze parameter recorded from one robust ideal observer bifurcate at a critical value of stimulus inconsistency. We report an experiment in which human observers also show this phenomenon and we use the experimentally determined critical value to estimate the vertical acuity of the visual system. The Bayesian analysis also provides a highly reliable and biologically plausible algorithm that can recover eye positions even before the classic stereo-correspondence problem is solved, that is, before deciding which features in the left and right images are to be matched.

Algorithms↗

A robust DNA mechanical device controlled by hybridization topology.

Controlled mechanical movement in molecular-scale devices has been realized in a variety of systems-catenanes and rotaxanes, chiroptical molecular switches, molecular ratchets and DNA-by exploiting conformational changes triggered by changes in redox potential or temperature, reversible binding of small molecules or ions, or irradiation. The incorporation of such devices into arrays could in principle lead to complex structural states suitable for nanorobotic applications, provided that individual devices can be addressed separately. But because the triggers commonly used tend to act equally on all the devices that are present, they will need to be localized very tightly. This could be readily achieved with devices that are controlled individually by separate and device-specific reagents. A trigger mechanism that allows such specific control is the reversible binding of DNA strands, thereby 'fuelling' conformational changes in a DNA machine. Here we improve upon the initial prototype system that uses this mechanism but generates by-products, by demonstrating a robust sequence-dependent rotary DNA device operating in a four-step cycle. We show that DNA strands control and fuel our device cycle by inducing the interconversion between two robust topological motifs, paranemic crossover (PX) DNA and its topoisomer JX2 DNA, in which one strand end is rotated relative to the other by 180 degrees. We expect that a wide range of analogous yet distinct rotary devices can be created by changing the control strands and the device sequences to which they bind.

Base Pairing↗

Robustness in simple biochemical networks.

Cells use complex networks of interacting molecular components to transfer and process information. These "computational devices of living cells" are responsible for many important cellular processes, including cell-cycle regulation and signal transduction. Here we address the issue of the sensitivity of the networks to variations in their biochemical parameters. We propose a mechanism for robust adaptation in simple signal transduction networks. We show that this mechanism applies in particular to bacterial chemotaxis. This is demonstrated within a quantitative model which explains, in a unified way, many aspects of chemotaxis, including proper responses to chemical gradients. The adaptation property is a consequence of the network's connectivity and does not require the 'fine-tuning' of parameters. We argue that the key properties of biochemical networks should be robust in order to ensure their proper functioning.

Adaptation, Physiological↗

Spatiotemporal regulation of MyD88-IRF-7 signalling for robust type-I interferon induction.

Robust type-I interferon (IFN-alpha/beta) induction in plasmacytoid dendritic cells, through the activation of Toll-like receptor 9 (TLR9), constitutes a critical aspect of immunity. It is absolutely dependent on the transcription factor IRF-7, which interacts with and is activated by the adaptor MyD88. How plasmacytoid dendritic cells, but not other cell types (such as conventional dendritic cells), are able to activate the MyD88-IRF-7-dependent IFN induction pathway remains unknown. Here we show that the spatiotemporal regulation of MyD88-IRF-7 signalling is critical for a high-level IFN induction in response to TLR9 activation. The IFN-inducing TLR9 ligand, A/D-type CpG oligodeoxynucleotide (CpG-A), is retained for long periods in the endosomal vesicles of plasmacytoid dendritic cells, together with the MyD88-IRF-7 complex. However, in conventional dendritic cells, CpG-A is rapidly transferred to lysosomal vesicles. We further show that conventional dendritic cells can also mount a robust IFN induction if CpG-A is manipulated for endosomal retention using a cationic lipid. This strategy also allows us to demonstrate endosomal activation of the IFN pathway by the otherwise inactive TLR9 ligand B/K-type oligodeoxynucleotide (CpG-B). Thus, our study offers insights into the regulation of TLR9 signalling in space, potentially suggesting a new avenue for therapeutic intervention.

Adaptor Proteins, Signal Transducing↗

Efficient and robust multiphoton data storage in molecular glasses and highly crosslinked polymers.

As electronics become ever faster and more powerful, there is growing interest in three-dimensional laser-based optical data storage techniques, which can potentially provide efficient storage at densities significantly higher than those that are likely to be available from magnetic media. The development of inexpensive, efficient and robust media has been a major obstacle in optical data storage. However, we have discovered a class of materials that become highly fluorescent on multiphoton absorption of pulses of 800-nm light from a Ti:sapphire oscillator, making them excellent candidate storage media. The materials are inexpensive, of high optical quality, can be processed readily, and can take a number of useful forms, including molecular glasses and highly crosslinked polymers. Three-dimensional data can be stored at high densities in these materials, and are highly robust to readout.

Electronics↗

Robust inference and correlates from genetic associations with personality.

Personality traits describe stable differences in how people think, feel and behave, and how they interact with and experience their social and physical environments1,2. Many questions remain unanswered about associations between DNA and personality traits, such as their robustness, their&#xa0;generalizability and the biological and social pathways through which they act. Here we meta-analyse data across 46 cohorts comprising 611,037 to 1.14&#x2009;million participants with European-like and African-like genomes for genome-wide association studies (GWAS) of the Big Five personality traits (extraversion, agreeableness, conscientiousness, neuroticism and openness to experience), and data from up to 50,725 participants for within-family GWAS. We identify 1,260 lead genetic variants associated with personality, including 824 novel variants3. Common genetic variants explain a moderate 4.8-9.3% of the variance in measures of each trait, and 9.3-13.3% among instruments with typical measurement reliability. Genetic associations with personality are highly consistent but not identical across geography, reporter (self versus close other), age group and measurement instrument, and we find minimal spousal assortment for personality in recent history. In contrast to many other social and behavioural traits4,5, within-family GWAS and polygenic index analyses indicate that genetic associations with personality are minimally confounded by the shared family environment. Polygenic prediction, genetic correlation and Mendelian randomization analyses indicate that personality traits have widespread, potentially causal associations with consequential behaviours and life outcomes. Overall, we find that the genetic architecture of personality is robustly generalizable, minimally confounded and widely relevant to human experience.

Journal Article↗

Compensatory evolution to DNA replication stress is robust to nutrient availability.

Evolutionary repair refers to the compensatory evolution that follows perturbations in cellular processes. While evolutionary trajectories are often reproducible, other studies suggest they are shaped by genotype-by-environment (GxE) interactions. Here, we test the predictability of evolutionary repair in response to DNA replication stress-a severe perturbation impairing the conserved mechanisms of DNA synthesis, resulting in genetic instability. We conducted high-throughput experimental evolution on Saccharomyces cerevisiae experiencing constitutive replication stress, grown under different glucose availability. We found that glucose levels impact the physiology and adaptation rate of replication stress mutants. However, the genetics of adaptation show remarkable robustness across environments. Recurrent mutations collectively recapitulated the fitness of evolved lines and are advantageous across macronutrient availability. We also identified a novel role of the mediator complex of RNA polymerase II in adaptation to replicative stress. Our results highlight the robustness and predictability of evolutionary repair mechanisms to DNA replication stress and provide new insights into the evolutionary aspects of genome stability, with potential implications for understanding cancer development.

DNA Replication↗

Robust QTL effect estimation using the minimum distance method.

Robustness has received little attention in QTL studies. We compare Maximum Likelihood (ML) and the Minimum Distance (MD) methods when there exists data contamination caused by outliers. A backcross population of size (N) 200 and 500 and 0, 5 or 25 outliers was simulated. The mean and standard deviation of the first QTL genotype were set to 1. Four cases were considered: (i) micro2=1, sigma2=1; (ii)micro2=1, sigma2=1.25; (iii) micro2=1.252, sigma2=1; (iv) micro2=1.282, sigma2=1.25, where micro2 and sigma2 are the mean and standard deviation of the second genotype. Either full or selective genotyping was considered. A Monte Carlo MD method is proposed to deal with missing genotypes. MD estimates were much more robust than ML estimates, especially with respect to scale parameter estimates, and with selective genotyping.

Genotype↗

Robustness of the extraction step when parallel factor analysis (PARAFAC) is used to quantify sulfonamides in kidney by high performance liquid chromatography-diode array detection (HPLC-DAD).

The robustness of a multiresidue method has been analysed for the extraction and quantification of sulfamethoxypyridazine, sulfamethoxazole and sulfadimethoxine in porcine kidney by HPLC-DAD through a Plackett-Burman design. Two experimental responses were examined, the mean recovery from three replicates (accuracy) and their standard deviation (precision). Three factors were tested: the volume of phosphoric acid (pH) added in the extraction step, the time used for passing the sample through the solid-phase extraction cartridge (flow rate) and methanol volume to elute the analytes from the cartridge. Due to the non-specificity of the chromatograms (unknown matrix interferences coelute with each sulfonamide) the PARAFAC model was employed to evaluate the concentration recovered in the experiments of the Plackett-Burman design as well as to identify the spectra of the substances according to the criteria set in the European Decision 2002/657/EC for the analysis of residues. The extraction step was concluded to be robust to the recovery and the standard deviation of all three analytes.

Animals↗

A hollow tetrahedral cage of hexadecagold dianion provides a robust backbone for a tuneable sub-nanometer oxidation and reduction agent via endohedral doping.

We show, via density functional theory calculations, that dianionic Au16(2-) cluster has a stable, hollow, Td symmetric cage structure, stabilized by 18 delocalized valence electrons. The cage maintains its robust geometry, with a minor Jahn-Teller deformation, over several charge states (q = -1,0,+1), forming spin doublet, triplet and quadruplet states according to the Hund's rules. Endohedral doping of the Au16 cage by Al or Si yields a geometrically robust, tuneable oxidation and reduction agent. Si@Au16 is a magic species with 20 delocalized electrons. We calculate a significant binding energy for the anionic Si@Au16/O2- complex and show that the adsorbed O2 is activated to a superoxo-species, a result which is at variance with the experimentally well-documented inertness of Au16- anion towards oxygen uptake.

Journal Article↗

Bistable reaction-diffusion systems can have robust zero-velocity fronts.

We show that for a class of bistable reaction-diffusion systems, zero-velocity fronts can be robust in the singular limit where one of the diffusion coefficients vanishes. In this case, stationary fronts can persist along variations of the system parameters. This property contrasts with the standard result that the front velocity v(&mgr;), expressed as a function of a control parameter &mgr;, is zero only at some isolated values &mgr;(0), and thus not giving robustness to zero-velocity fronts when &mgr; is varied. (c) 2000 American Institute of Physics.

Journal Article↗

W3 theory: robust computational thermochemistry in the kJ/mol accuracy range.

We are proposing a new computational thermochemistry protocol denoted W3 theory, as a successor to W1 and W2 theory proposed earlier [Martin and De Oliveira, J. Chem. Phys. 111, 1843 (1999)]. The new method is both more accurate overall (error statistics for total atomization energies approximately cut in half) and more robust (particularly towards systems exhibiting significant nondynamical correlation) than W2 theory. The cardinal improvement rests in an approximate account for post-CCSD(T) correlation effects. Iterative T3 (connected triple excitations) effects exhibit a basis set convergence behavior similar to the T3 contribution overall. They almost universally decrease molecular binding energies. Their inclusion in isolation yields less accurate results than CCSD(T) nearly across the board: It is only when T4 (connected quadruple excitations) effects are included that superior performance is achieved. T4 effects systematically increase molecular binding energies. Their basis set convergence is quite rapid, and even CCSDTQ/cc-pVDZ scaled by an empirical factor of 1.2532 will yield a quite passable quadruples contribution. The effect of still higher-order excitations was gauged for a subset of molecules (notably the eight-valence electron systems): T5 (connected quintuple excitations) contributions reach 0.3 kcal/mol for the pathologically multireference X 1Sigmag+ state of C2 but are quite small for other systems. A variety of avenues for achieving accuracy beyond that of W3 theory were explored, to no significant avail. W3 thus appears to represent a good compromise between accuracy and computational cost for those seeking a robust method for computational thermochemistry in the kJ/mol accuracy range on small systems.

Journal Article↗

Robust discretizations versus increase of the time step for the Lorenz system.

When continuous systems are discretized, their solutions depend on the time step chosen a priori. Such solutions are not necessarily spurious in the sense that they can still correspond to a solution of the differential equations but with a displacement in the parameter space. Consequently, it is of great interest to obtain discrete equations which are robust even when the discretization time step is large. In this paper, different discretizations of the Lorenz system are discussed versus the values of the discretization time step. It is shown that the sets of difference equations proposed are more robust versus increases of the time step than conventional discretizations built with standard schemes such as the forward Euler, backward Euler, or centered finite difference schemes. The nonstandard schemes used here are Mickens' scheme and Monaco and Normand-Cyrot's scheme.

Algorithms↗